journal,title,abstract,doi,publication_date,route_prob
Tetrahedron,Stereocontrolled route to a key intermediate for the synthesis of maytansine,,10.1016/s0040-4039(00)75203-8,1975-01-01,0.8384093314328794
Organic Process Research & Development,Practical Synthesis of a HIV Integrase Inhibitor,"A practical and efficient synthesis of the potent HIV integrase inhibitor 1 is described. Starting from readily available 3,4-dihydro-2 H -pyran, the six-step synthesis features a through process without purification of any of the intermediates until the isolation of crystalline intermediate 7 . After deprotection and classical resolution, amine 8 was isolated with excellent enantiopurity. A final amide coupling completed the synthesis of 1 in 7.6% overall yield from DHP. This chromatography-free route is more cost effective and increases the overall yield by nearly 3 times when compared with the original Med Chem synthethic route. This improved chemistry was used successfully to prepare multikilogram quantities of integrase inhibitor 1 .",10.1021/op800153y,2008-10-29,0.8299941072417972
Tetrahedron,An expeditious route to the synthesis of adenophostin A,,10.1016/0040-4039(96)00632-6,1996-05-01,0.8182425597713059
Organic Process Research & Development,Development of a Scalable Route to the SMO Receptor Antagonist SEN794,"A practical and scalable route to the SMO receptor antagonist SEN794 1 is described herein. A new and efficient access to the key intermediate 7 via the Kröhnke reaction was developed, significantly simplifying the synthesis and reducing costs. The optimized route consists of six chemical steps plus a palladium scavenging step. The intermediates are solids and were isolated by filtrations, except for ester 9, which was telescoped as the crude oil into the subsequent step. In the final amide formation step, target compound 1 was conveniently crystallized from the reaction mixture in high purity.",10.1021/op300170q,2012-10-31,0.8143217241002475
Tetrahedron,A highly efficient route to a key intermediate for the synthesis of prostaglandins,,10.1016/s0040-4039(01)84252-0,1972-01-01,0.8097718154940541
Tetrahedron,A new synthetic route to (±)-vindoline. A synthesis of the bchi's tetracyclic intermediate,,10.1016/s0040-4039(01)85069-3,1978-01-01,0.8095797902519567
Tetrahedron,An efficient route for synthesis of spirocyclic cyclopentapyridines,,10.1016/j.tetlet.2024.155250,2024-08-14,0.8075266879347426
Tetrahedron,Synthesis of combretastatin D-2. An efficient route to caffrane macrolactones,,10.1016/s0040-4039(00)73369-7,1994-06-01,0.8075266879347426
Organic Process Research & Development,"Convergent, Fit-For-Purpose, Kilogram-Scale Synthesis of a 5-Lipoxygenase Inhibitor",Process research and development of a synthetic route towards a novel 5-lipoxygenase inhibitor is described. The synthetic route provided 1 in 27% yield in nine steps (seven steps in the longest linear sequence) and was performed on kilogram scale. The synthesis began with the preparation of the coumarin core via an efficient von Pechmann condensation. The triazole fragment was obtained via a regioselective copper-catalyzed [3 + 2] cycloaddition between a chiral alkyne and the coumarin azide.,10.1021/op200299p,2012-01-05,0.806384636427652
Organic Process Research & Development,Development and a Practical Synthesis of the JAK2 Inhibitor LY2784544,"The route selection and process research and development of a practical synthesis for JAK2 inhibitor LY2784544 is described. The first-generation synthesis route, similar to that used in discovery for derivatization of a benzylic amine moiety, was 14 overall steps and possessed several steps that required extensive development for large-scale production. Route selection considerations led to a modified synthesis that utilized a novel vanadium-catalyzed carbon–carbon bond-forming arylation reaction for incorporation of the key benzylic morpholine moiety. A protecting group used to mask an amino pyrazole unit was modified from PMB to tert -butyl, resulting in a dramatic reduction in the overall length of the route. These two major changes resulted in an eight-step synthesis, which was six steps shorter than the first-generation synthesis. In the pilot plant, the new synthesis was scaled to produce >100 kg of LY2784544 in high yield and purity under GMP conditions. The overall development including the vanadium-catalyzed C–C bond-forming methodology, a ketone reductive deoxygenation, and a palladium-catalyzed amination is described.",10.1021/op200229j,2011-10-22,0.8061839414129941
Organic Process Research & Development,Practical and Efficient Synthesis of 2-Thio-imidazole Derivative—<b>ZY12201</b>: A Potent TGR5 Agonist,"Early scalable process development for the synthesis of ZY12201, a novel TGR5 receptor agonist, as a potential clinical candidate is described. A practical, efficient, and scalable synthetic route provided ZY12201 in seven steps and 32% overall yield. The key step involves an inexpensive acetic acid-mediated cyclization of thiourea 6 for the construction of 2-thio-imidazole derivative 7 . The developed process demonstrated cost-effective, high-yielding, kilogram-scalable, and environmentally friendly synthesis of ZY12201. This high-yielding route enabled us to rapidly synthesize large quantities of ZY12201 in 99% purity to support in vivo and toxicity studies.",10.1021/acs.oprd.0c00234,2020-07-30,0.8041197141374785
Organic Process Research & Development,Synthesis of Akt Inhibitor Ipatasertib. Part 1. Route Scouting and Early Process Development of a Challenging Cyclopentylpyrimidine Intermediate,"Herein, the route scouting and early process development of a key cyclopentylpyrimidine ketone intermediate toward the synthesis of Akt inhibitor Ipatasertib are described. Initial supplies of the intermediate were prepared through a method that commenced with the natural product ( R )-(+)-pulegone and relied on the early construction of a methyl-substituted cyclopentyl ring system. The first process chemistry route, detailed herein, enabled the synthesis of the ketone on a hundred-gram scale, but it was not feasible for the requisite production of multikilogram quantities of this compound and necessitated the exploration of alternative strategies. Several new synthetic approaches were investigated towards the preparation of the cyclopentylpyrimidine ketone, in either racemic or chiral form, which resulted in the discovery of a more practical route that hinged on the initial preparation of a highly substituted dihydroxypyrimidine compound. The cyclopentane ring in the target was then constructed through a key carbonylative esterification and subsequent tandem Dieckmann cyclization–decarboxylation sequence that was demonstrated in a racemic synthesis. This proof-of-concept was later developed into an asymmetric synthesis of the cyclopentylpyrimidine ketone, which will be described in a subsequent paper, along with the synthesis of Ipatasertib.",10.1021/op500271w,2014-10-26,0.8024123194625618
Tetrahedron,An improved route for the synthesis of Rolloamide B,,10.1016/j.tetlet.2016.07.044,2016-07-16,0.8006930651100604
Tetrahedron,An improved route to isoquinolines; synthesis of the alkaloids escholamine and takatonine.,,10.1016/s0040-4039(01)94429-6,1972-01-01,0.8006930651100604
Tetrahedron,"New synthetic route to 2,2,6,6-tetraethylpiperidin-4-one: A key-intermediate towards tetraethyl nitroxides",,10.1016/j.tetlet.2019.151207,2019-09-26,0.8006816426279578
Organic Process Research & Development,Development of a Practical and Scalable Synthesis of a Potent CRTH2 Antagonist,"This contribution describes the process research and development of a practical and scalable synthetic method towards compound 1, which has a potent CRTH2 antagonistic activity. The medicinal chemistry synthetic route and second generation synthetic route had several issues in scale-up synthesis. In contrast, the synthetic method described here does not require purification by column chromatography for all steps, and the formation of impurities is suppressed well. This highly efficient and scalable process was successfully demonstrated in the large-scale synthesis of 1 .",10.1021/op3001492,2012-08-09,0.8004716573571549
Tetrahedron,A new route to the emetine alkaloids intending for a chiral synthesis A synthesis of (dl)-protoemetinol and a formal synthesis of (dl)-emetine from (dl)-norcamphor,,10.1016/0040-4039(78)80020-3,1978-07-01,0.7977713227347313
Tetrahedron,A new route to the emetine alkaloids intending for a chiral synthesis. A synthesis of (dl)-protoemetinol and a formal synthesis of (dl)-emetine from (dl)-norcamphor,,10.1016/s0040-4039(01)94815-4,1978-01-01,0.7977713227347313
Synlett,Development of a Scalable Synthesis of a VEGFR Inhibitor,"Process development and salt selection for a novel ­VEGFR inhibitor are described. The overall convergent synthesis involved coupling of three key fragments, 2-chloronicotinoyl chloride, 4-isopropyl-3-methylaniline and 7-aminoisoquinoline. A cost-effective and scalable synthesis of 7-aminoisoquinoline was also achieved. A transition-metal-free S N Ar process enabled the final C–N coupling to afford the target molecule. A phosphate form of the drug substance with improved physical properties was selected for further development and the corresponding crystallization process was subsequently developed. Overall, a robust six-step route was developed and demonstrated on multikilogram scales affording the target compound in >30% yield and high purity (>99%).",10.1055/s-0032-1317554,2012-11-16,0.7976937249166126
Journal of Organic Chemistry,"Design of Concise, Scalable Route to a Cholecystokinin 1 (CCK 1) Receptor Antagonist","Development of efficient, scalable routes for the synthesis of (S)-3-[5-(3,4-dichlorophenyl)-1-(4-methoxyphenyl)-1H-pyrazol-3-yl]-2-m-tolyl propionic acid, a selective cholecystokinin 1 (CCK 1) receptor antagonist, is described. A key feature of the scale-up route is a concise construction of the complete pyrazole framework in a single step by reacting an aryl hydrazine with an elaborated acetylenic ketone. This route was then further refined incorporating efficient enantioselective strategies to obtain the desired S-enantiomer in high optical purity. The first strategy involved an efficient, recyclable, kinetic resolution by enzyme-catalyzed hydrolysis of the racemic ester. In the second-generation route, the requisite stereochemistry at the chiral center was generated at an early stage in the synthesis involving a remarkable diastereoselective addition of inexpensive (S)-(-)-ethyl lactate to an alkylaryl ketene. Both methods furnished optically pure (>99% ee) final drug substance as its crystalline sodium salt.",10.1021/jo071166m,2007-09-22,0.7971033972250412
Organic Process Research & Development,An Improved Synthetic Route for Preparative Process of Vardenafil,"A new, convergent synthetic route for the process optimization of vardenafil (Levitra), a potent and effective PDE5 inhibitor, is described. Key improved steps in the preparative process are that the chlorosulfonation reaction is at the beginning and the dehydration-cyclisation reaction is at a later stage so that the synthetic route has a better overall yield and simpler workup operations. The yield of vardenafil produced from this synthetic route is around 45% over seven steps with purity at 99.2% (HPLC).",10.1021/op900235p,2009-11-02,0.7963886081643117
Organic Process Research & Development,Development of a Practical and Scalable Synthesis of a Potent Selective Dual Antagonist for 5-HT2B and 5-HT7 Receptors,"Process research and development of a practical and scalable synthetic route toward compound ( S ) - 1 and compound ( R ) - 1, which are potent selective dual antagonists for 5-HT2B and 5-HT7 receptors, respectively, is described. The medicinal chemistry route and second generation route were also unattractive for large-scale use for a variety of reasons. The new synthetic method does not require any purification by column chromatography for all steps and highly exothermic reactions. Additionally, we developed an efficient method of optical resolution in which each carboxylic acid isomer was separated with chiral amine in high yield and high enantiopurity. This highly efficient and scalable process was successfully demonstrated in the large scale synthesis of compound ( S ) - 1 and compound ( R ) - 1 in high enantiopurity.",10.1021/op200380z,2012-04-05,0.7946326037061435
Tetrahedron,A practical and efficient synthesis of the ziegler key intermediate for the synthesis of forskolin,,10.1016/s0040-4039(00)94328-4,1990-01-01,0.7944808412899427
Tetrahedron,"Efficient and practical synthesis of d-cyclopent-2-enone, the key intermediate for the synthesis of carbocyclic nucleosides",,10.1016/s0040-4039(02)00774-8,2002-06-01,0.7944808412899427
Organic Process Research & Development,"Development of a Practical and Scalable Synthetic Route to YM758 Monophosphate, A Novel I<sub>f</sub> Channel Inhibitor","A novel, practical, and efficient synthesis of (−)- N -{2-[( R )-3-(6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-2-carbonyl)piperidino]ethyl}-4-fluorobenzamide monophosphate (YM758 monophosphate, ( R )-1·H 3 PO 4 (Figure 1 ) is described. The target molecule ( R )-1 has a potent I f current channel inhibitor. Medicinal chemistry synthetic routes were very long and suffered from extensive use of chlorinated solvents and silica-gel column chromatography. A number of steps in the medicinal chemistry route were also unattractive for large-scale synthesis due to some reasons for example the use of unstable intermediates. An important objective of a new synthetic route was avoidance of such a use of unstable intermediate, and it was achieved by the discovery of an important 4,5-dihydrooxazole intermediate 19 and ring-opening N -alkylation of chiral amine with 19 under acidic condition. The new procedure does not require any purification by column chromatography for all steps. The overall yield was significantly improved from 14% or 34% to 49% compared to that of the medicinal synthetic routes. This highly efficient process was successfully demonstrated at a pilot-scale operation, yielding 36.5 kg of ( R )-1·H 3 PO 4 .",10.1021/op5002885,2014-10-17,0.7939134908652689
Organic Process Research & Development,"An Efficient Synthesis of 1-(2-Methoxyphenoxy)-2,3-epoxypropane: Key Intermediate of β-Adrenoblockers","An efficient process for the preparation of 1-(2-methoxyphenoxy)-2,3-epoxypropane, a key intermediate for the synthesis of ranolazine is described.",10.1021/op300056k,2012-09-14,0.7937121181022587
Organic Process Research & Development,From Chiral Resolution to Diastereoselective Ellman Chemistry to Biocatalysis: Route Evolution for the Efficient Synthesis of the Tetrahydrobenzoazepine Core of BTK Inhibitor BIIB091,"Two improved routes to BIIB091 key tetrahydrobenzoazepine core ( 1 ) were developed to support tox and early clinical demands. The first improved route takes advantage of a diastereoselective Ellman’s sulfinimine reduction as the key step of chiral amine synthesis. This route was successfully scaled up to support API manufacturing for early clinical trials. The second improved route uses an amine transaminase (ATA) biocatalysis reaction of an N-Boc ketone ( 15 ) precursor, which was prepared by applying a trifluoroacetamide-protecting group for effective azepine ring construction and protecting group swap. The ATA route is demonstrated at a subkilogram scale and has the potential to become a late clinical and commercial route due to its significant improvements in synthetic efficiency, overall yield, and process greenness.",10.1021/acs.oprd.3c00133,2023-07-18,0.7929244634649086
Tetrahedron,A new route to the zizaane sesquiterpenes: An efficient synthesis of (±)-isokhusimone,,10.1016/s0040-4039(00)80497-9,1988-01-01,0.792057446587325
Organic Process Research & Development,Process Development of an Efficient and Cost-Effective Telescoping Route to a Key Synthetic Precursor for the Preparation of a Renin Inhibitor,"Here, we describe an efficient and cost-effective telescoping route to the pharmacologically active form ( 2 ), which is a key manufacturing precursor to a novel renin inhibitor for the treatment of hypertension. An efficient synthetic route to the target compound was established with 64% overall yield over nine steps with three isolations.",10.1021/acs.oprd.8b00414,2019-02-19,0.7914619889784932
Organic Process Research & Development,Development of a Practical Synthesis of a p38 Kinase Inhibitor via a Safe and Robust Amination,"The development of a practical synthesis for a p38 kinase inhibitor is described. The key advances include an improved route to the key intermediate, a substituted pyrrole, and a subsequent animation utilizing O -(4-nitrobenzoyl)hydroxylamine, which provides a safe, scalable, and robust amination method. The new protocol was successfully demonstrated to generate 1.6 kg of API in seven steps and 26% overall yield.",10.1021/op300181r,2012-08-31,0.791245803568979
Synlett,A Further Improved Synthesis of a Dibenzodioxocinone CETP Inhibitor,A newly improved synthesis of a dibenzodioxocinone CETP inhibitor is described. Key features of the synthetic route include a chiral ligand induced alkyl addition to aldehyde and the use of triethylborane for improved selective alkylation of brominated phenyl ring.,10.1055/s-0029-1217757,2009-09-03,0.7910312906269328
Journal of Organic Chemistry,"Development of a Convergent Large-Scale Synthesis for Venetoclax, a First-in-Class BCL-2 Selective Inhibitor","The process development of a new synthetic route leading to an efficient and robust synthetic process for venetoclax (1: the active pharmaceutical ingredient (API) in Venclexta) is described. The redesigned synthesis features a Buchwald-Hartwig amination to construct the core ester 23c in a convergent fashion by connecting two key building blocks (4c and 26), which is then followed by a uniquely effective saponification reaction of 23c using anhydrous hydroxide generated in situ to obtain 2. Finally, the coupling of the penultimate core acid 2 with sulfonamide 3 furnishes drug substance 1 with consistently high quality. The challenges and solutions for the key Pd-catalyzed C-N cross-coupling will also be discussed in detail. The improved synthesis overcomes many of the initial scale-up challenges and was accomplished in 46% overall yield from 3,3-dimethyldicyclohexanone (6), more than doubling the overall yield of the first generation route. The new process was successfully implemented for producing large quantities of 1 with >99% area purity.",10.1021/acs.joc.8b02750,2019-01-07,0.7904561992482018
Organic Process Research & Development,A Scalable Route to 5-Substituted 3-Isoxazolol Fibrinolysis Inhibitor AZD6564,"A practical and chromatography-free multikilogram synthesis of a 3-isoxazolol containing antifibrinolytic agent, AZD6564, has been developed in eight steps and 7% overall yield starting from methyl 2-chloroisonicotinate. Highlights in the synthesis are a Negishi coupling and an enzymatic resolution of a racemic ester.",10.1021/op500193s,2014-08-06,0.7902134711011278
Synlett,Kilogram Synthesis of (S)-3-Aminopyran from l-Glutamic Acid,"We describe the development of a concise route to prepare kilogram quantities of ( S )-3-aminopyran, a key intermediate in the synthesis of a Jak1 inhibitor. The chiral amine was introduced via a chiral-pool approach and involves using inexpensive, commercially available l -glutamic acid as the key starting material. Global protection, followed by reduction afforded the N -Boc-amino diol. Intramolecular Mitsunobu cyclization and deprotection afforded the desired compound in 30% overall yield over four steps without the use of chromatography.",10.1055/s-0033-1338422,2013-04-10,0.7892034585843293
Organic Process Research & Development,Development of Kilogram-Scale Synthesis of EGFR Inhibitor EAI045,"Herein, we report a synthetic route for an EGFR inhibitor, 2-(5-fluoro-2-hydroxyphenyl)-2-(1-oxoisoindolin-2-yl) acetic acid (EAI045), using a three-step approach. This short and efficient route is the first report of a scalable process for EAI045, which employs a convergent three-component coupling strategy as the key step, producing EAI045 in good yield on kilogram scale.",10.1021/acs.oprd.8b00276,2019-01-15,0.7885375356099239
Organic Process Research & Development,A Scalable Route to the SMO Receptor Antagonist SEN826: Benzimidazole Synthesis via Enhanced in Situ Formation of the Bisulfite–Aldehyde Complex,"A practical and scalable route to the SMO antagonist SEN826 1 is described herein, including the discussion of an alternative approach to the synthesis of the target molecule. The optimized route consists of five chemical steps. A new and efficient access to the key intermediate 6 via the bisulfite–aldehyde complex was developed, significantly enhancing the yields and reducing costs. As a result, a synthetic procedure for preparation of multihundred gram quantities of the final product has been developed.",10.1021/op4002092,2014-05-19,0.787638545495256
Organic Process Research & Development,"Development of a Scalable Synthesis of a Vascular Endothelial Growth Factor Receptor-2 Kinase Inhibitor: Efficient Construction of a 6-Etherified [1,2,4]Triazolo[1,5-<i>a</i>]pyridine-2-amine Core","A practical and scalable synthesis of the vascular endothelial growth factor receptor-2 (VEGFR-2) kinase inhibitor 1 has been developed. The key features of the process development include facile preparation of the key raw material 3-amino-4-fluorophenol, chemoselective nucleophilic aromatic substitution of 5-chloro-2-nitropyridine with phenol, a safe one-pot synthesis of a substituted urea using an isothiocyanate generated in situ from inexpensive materials, and improvement of the yield of acylation in the end game. The optimized six-step synthesis afforded 1 ·H 2 O in 54% overall yield, twice as much as the yield of the original synthesis, without chromatographic purification. In addition, a robust recrystallization procedure to afford the desired crystal form of 1 was also developed.",10.1021/op4002824,2013-12-19,0.7871167103479667
Journal of Organic Chemistry,"A Short Enantioselective Synthesis of <i>N</i>-Boc-(2<i>R</i>,3<i>R</i>)-3-Methyl-3-Hydroxypipecolic Acid from Geraniol","The asymmetric synthesis of (2R,3R)-3-methyl-3-hydroxypipecolic acid, a key intermediate in the synthesis of dual MMP-13/aggrecanase inhibitors, is described. The title compound is prepared in seven steps with an overall yield of 41% starting from geraniol. Key steps in the synthesis include Sharpless asymmetric epoxidation, which establishes the chiral centers, and a one-pot oxidative olefin cleavage/reductive amination sequence that closes the piperidine ring.",10.1021/jo800080t,2008-03-14,0.7857386573287007
Organic Process Research & Development,Development of a Robust Scale-Up Synthetic Route for BPR1K871: A Clinical Candidate for the Treatment of Acute Myeloid Leukemia and Solid Tumors,"High Resolution Image Download MS PowerPoint Slide Herein, a robust and scalable procedure for the synthesis of multikinase inhibitor BPR1K871 ( 1, a quinazoline compound bearing a substituted thiazoline side chain), which is a clinical candidate for the treatment of acute myeloid leukemia and solid tumors, is reported. The previously reported medicinal chemistry synthetic route A with seven steps had encountered several issues during scale-up syntheses such as low yields (7.7% overall yield), the formation of inseparable impurities, particularly in the chlorination step, use of hazardous reagents (NaH/DMF), and laborious column chromatography steps for the purification of the products. A step-by-step approach to overcome the above issues was planned and implemented through two similar routes (B1 and B2) on a gram scale and finally through route B3 on a kilogram scale to synthesize 1 . The final optimized synthetic route B3 does not require column chromatography purification steps. It is one step shorter than the original route A and avoided hazardous reagents for the alkylation reaction in step 2. Furthermore, the highlights of the new route B3 include liquid–liquid continuous extraction of compound 13 in step 2, the use of POCl 3 instead of SOCl 2 to minimize the formation of impurities in the chlorination step 3, and telescoped synthesis of key Boc-protected amino intermediate 15 from 13, in high purity. Using the scale-up route B3, the final product 1 (3.09 kg, yield of 16.5% over six steps with an HPLC purity of 97.8%) was obtained in a single batch for preclinical testing and facilitated clinical testing of 1, which is underway.",10.1021/acs.oprd.0c00515,2021-02-18,0.7856123361900748
Synlett,"Development of a Practical Synthesis of 4-[6-(Morpholinomethyl)-pyridin-3-yl]naphthalen-1-amine, a Key Intermediate for the Synthesis of BIRB 1017, a Potent p38 MAP Kinase Inhibitor","The development of synthetic routes to 4-[6-(morpholinomethyl)pyridin-3-yl]naphthalen-1-amine, the key intermediate of p38 MAP kinase inhibitor BIRB 1017, via (1) trialkylmagnesium ate complex mediated metalation and borylation followed by Suzuki coupling reactions and (2) pyridine-ring formation from a vinamidinium salt, is described.",10.1055/s-0032-1317790,2013-01-11,0.7846361035600278
Tetrahedron,Cypridina bioluminescence VI a new route for the synthesis of cypridina luciferin and its analogs,,10.1016/s0040-4039(01)87958-2,1969-01-01,0.7843220626039793
Tetrahedron,Synthesis of iPF2α-V: a new route,,10.1016/s0040-4039(99)01144-2,1999-08-01,0.7843220626039793
Tetrahedron,"Exploitation of a new route to fused pyrroles: Synthesis of TNP-351, homo-MTA and 5-arylpyrrolo[2,3-]pyrimidines",,10.1016/s0040-4039(99)00677-2,1999-05-01,0.7843220626039793
Tetrahedron,"The first route toward oxygenated monocarbocyclic terpenoids: synthesis of elegansidiol, a new sesquiterpene from Santolina elegans",,10.1016/s0040-4039(99)01730-x,1999-11-01,0.7843220626039793
Tetrahedron,"The synthesis of tricyclo[4.3.0.03,8]Nonane (twist-brendane) and homoadamantane. A new route to homoadamantanes",,10.1016/s0040-4039(01)99006-9,1968-01-01,0.7843220626039793
Tetrahedron,"A new route to eremophilanes: synthesis of (±)-eremophilenolide, (±)-eremophiledinone, and (±)-deoxyeremopetasidione",,10.1016/j.tetlet.2008.08.006,2008-08-13,0.7843220626039793
Tetrahedron,A new and unusually flexible route to cyclopentanoids synthesis of sarkomycin and prostaglandins,,10.1016/s0040-4039(00)99968-4,1984-01-01,0.7843220626039793
Tetrahedron,A new route to 1-oxygenated carbazoles. Synthesis of murrayafoline-a,,10.1016/s0040-4039(00)98941-x,1985-01-01,0.7843220626039793
Tetrahedron,A new route to the synthesis of ellipticine quinone from isatin,,10.1016/j.tetlet.2013.12.098,2014-01-01,0.7843220626039793
Tetrahedron,The -quinodimethane route to anthracyclinones a new synthesis of 4-demethoxydaunomycinone,,10.1016/s0040-4039(01)95053-1,1978-01-01,0.7843220626039793
Organic Process Research & Development,"Process Development of the Pyrazinecarboxamide Component of Gilteritinib, a FLT3 Inhibitor","Gilteritinib (ASP2215) is an inhibitor of the mutated FMS-like tyrosine kinase 3 (FLT3) for the treatment of relapsed or refractory acute myeloid leukemia. Discovery chemistry identified a key pyrazinecarboxamide intermediate, 3,5-dichloro-6-ethylpyrazine-2-carboxamide, in the synthesis of gilteritinib. However, the four-step route to the intermediate from 2,6-dichloropyrazine required cryogenic conditions and column chromatography and was therefore not appropriate for large-scale synthesis to cover all of the material requirements of the final active pharmaceutical ingredient, gilteritinib, for early stage development thereof. To address these issues urgently and determine a scalable synthetic route to the key compound, a thorough process investigation was undertaken, and the efficient second route starting from methyl 3-oxopentanoate was successfully discovered. Highlights of the newly developed route included (1) higher throughput and overall yield compared to the discovery route, (2) no requirement for cryogenic conditions or column chromatography, (3) avoidance of heavy metals, and (4) minimization of waste generation compared to the discovery route. Furthermore, scale-up studies especially from a safety standpoint were implemented for the second-generation route prior to the first production. These investigations enabled us to produce a single 125 kg batch of the key intermediate in a greatly shortened lead time by the cyclization strategy from readily available methyl 3-oxopentanoate, which contributed to the early stage development and future commercial synthesis of gilteritinib.",10.1021/acs.oprd.4c00119,2024-05-24,0.78413274637962
Tetrahedron,"Synthesis of 3,9-dialkylguanines and 3-methylguanosine, a key intermediate for the synthesis of Y nucleosides",,10.1016/s0040-4039(01)94895-6,1978-01-01,0.7841272792591557
Synthesis,A Novel Route for the Synthesis of<i>endo</i>-Polynuclear Heterocycles,,10.1055/s-1978-24771,1978-01-01,0.7838154989948474
Tetrahedron,"Synthesis of 2′,3′-dideoxy-3′-hydroxymethylcytidine: A novel hydroformylation route",,10.1016/s0040-4039(97)00142-1,1997-03-01,0.7838154989948474
Tetrahedron,Novel route to the synthesis of 4-quinolyl isothiocyanates,,10.1016/j.tetlet.2006.01.119,2006-02-16,0.7838154989948474
Tetrahedron,Enantiospecific synthesis of 3-pyrrolines: A route to novel polyhydroxylated pyrrolidines,,10.1016/0040-4039(94)88236-3,1994-09-01,0.7838154989948474
Organic Process Research & Development,Development of a Synthetic Process towards a Hepatitis C Polymerase Inhibitor,"The synthesis of 2-(4-{2-[(2 R )-2-Cyclopentyl-5-(5,7-dimethyl-[1,2,4]triazolo[1,5-a]pyrimidin-2-ylmethyl)-4-hydroxy-6-oxo-3,6-dihydro-2H-pyran-2-yl]-ethyl}-2-fluoro-phenyl)-2-methyl-propionitrile ( 1 ) on multikilogram scale is described. Initial synthesis of this clinical candidate for inhibition of the hepatitis C viral polymerase (HCVP) protein was executed via a racemic synthetic route coupled with chiral HPLC separation. Due to the achiral route and instability of key intermediates, the initial route was determined to be unsuitable for large-scale manufacture. An alternate route was developed utilizing a convergent Heck coupling, resolution of a carboxylic acid via diastereomeric salt formation, and an efficient chemical recycling of the undesired enantiomer.",10.1021/op0600761,2006-06-15,0.7827477199565991
Synthesis,A New and Practical Synthesis of Vortioxetine Hydrobromide,A new and improved synthetic route to vortioxetine hydrobromide is established on a hectogram scale through three simple steps in 63% yield and with 99% purity (HPLC). The key step is the cyclization of the piperazine ring in the final step. Purification methods for the intermediates involved in the route are given.,10.1055/s-0034-1380505,2015-04-13,0.7825948314642684
Organic Process Research & Development,"Discovery of a Novel, Efficient, and Scalable Route to Bendamustine Hydrochloride: The API in Treanda","Process Research and Development activities leading to a new and efficient route to bendamustine hydrochloride, 1, the active ingredient in Treanda, a treatment for blood cancers, are disclosed. Two key features of this new process include a one-pot hydrogenation/dehydration sequence to construct the benzimidazole moiety and a novel reductive alkylation using chloroacetic acid and borane to install the bischloroethyl side chain. The number of synthetic steps has been significantly reduced to five from the eight in the current commercial process. The overall yield has been improved from 12% to 45%. Additionally, this new route eliminates chloroform, ethylene oxide, and sodium sulfide. Scale-up of the new route has been successfully demonstrated to prepare kilogram quantities of bendamustine hydrochloride.",10.1021/op200176f,2011-08-13,0.7825892940986854
Journal of Organic Chemistry,Practical and Scalable Synthesis of a Selective CCK<sub>1</sub> Receptor Antagonist,"We describe a practical and scalable route to compound (Z)-1, a selective CCK1 receptor antagonist. Notable features of this concise route are (1) a regioselective construction of the pyrazole core through the reaction of an aryl hydrazine and an elaborated acetylenic ketone, (2) a Tf2O/pyridine mediated Z-selective dehydration of an α-hydroxyester, and (3) a stereoselective hydrolysis. The sequence is high-yielding and amenable for large-scale synthesis.",10.1021/jo1017684,2010-10-27,0.7819328210999547
Organic Process Research & Development,Practical Convergent Laboratory-Scale Synthesis of a CCR5 Receptor Antagonist,"An efficient laboratory-scale synthesis has been developed for the selective CCR5 antagonist 1 . The convergent route has a longest linear sequence of nine steps (15 steps overall), and has overall yields of 18–25%. The route has enabled the preparation of 550 g of 1 .",10.1021/op200259t,2011-10-29,0.7815643233964796
Tetrahedron,Biomimetic total synthesis of the ACAT inhibitor (+)-pyripyropene E,"The acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor (+)-pyripyropene E (1) has been synthesized from farnesyl acetate (9 steps, 9.6% overall yield). The convergent and stereoselective route exploited a biomimetic polyene cyclization as the key transformation.",10.1016/0040-4039(96)01439-6,1996-09-01,0.7810027592647047
Organic Process Research & Development,Process Development and Scale-Up of a Benzoxazepine-Containing Kinase Inhibitor,"The benzoxazepine core is present in several kinase inhibitors, including the mTOR inhibitor 1 . The process development for a scalable synthesis of 7-bromobenzoxazepine and the telescoped synthesis of 1 are reported. Compound 1 consists of three chemically rich, distinct fragments: the tetrahydrobenzo[ f ][1,4]oxazepine core, the aminopyridyl fragment, and the substituted (methylsulfonyl)benzoyl fragment. Routes were developed for the preparation of 3-fluoro-2-methyl-4-(methylsulfonyl)benzoic acid ( 17 ) and tert -butyl 7-bromo-2,3-dihydrobenzo[ f ][1,4]oxazepine-4(5 H )-carboxylate ( 2 ). The processes for the two compounds were scaled up, and over 15 kg of each starting material was prepared in overall yields of 42% and 58%, respectively. A telescoped sequence beginning with compound 2 afforded 7.5 kg of the elaborated intermediate 5-(2,3,4,5-tetrahydrobenzo[ f ][1,4]oxazepin-2-amine dihydrochloride ( 6 ) in 63% yield. Subsequent coupling with benzoic acid 17 gave 7.6 kg of the target compound 1 in 84% yield. The preferred hydrochloride salt was eventually prepared. The overall yield for the synthesis of inhibitor 1 was 21% over eight isolated synthetic steps, and the final salt was obtained with 99.7% HPLC purity.",10.1021/acs.oprd.5b00037,2015-04-29,0.7804927904152423
Tetrahedron,"Efficient synthesis of prasugrel, a novel P2Y12 receptor inhibitor",,10.1016/j.tetlet.2012.07.071,2012-07-26,0.7793506102337058
Organic Process Research & Development,Novel Preparation of H<sub>1</sub> Receptor Antagonist Fexofenadine,"A novel synthetic route for the preparation of H 1 receptor antagonist fexofenadine is described. The synthetic route started from the para-substituted aromatic derivative of methyl 4-(cyanomethyl)benzoate, 2, and gave fexofenadine in 26.0% overall yield via six steps. The whole process featured a method wherein fexofenadine could be obtained in excellent quality without ortho- or meta-unpurified regioisomers.",10.1021/op100090j,2010-10-04,0.7786893404305243
Organic Process Research & Development,Synthesis Development of the Selective Estrogen Receptor Degrader (SERD) LSZ102 from a Suzuki Coupling to a C–H Activation Strategy,"The development of the synthetic process to the selective estrogen receptor degrader (SERD) drug candidate LSZ102 from the medicinal chemistry synthesis to the streamlined large-scale manufacturing route is described. The synthesis of LSZ102 could be significantly improved in regard to overall yield, removal of all chromatographic purifications, and reduction in the number of steps by revisiting the original disconnection strategy. Key features of the final process include construction of the benzothiophene core via Higa cyclization, late-stage phenolation using a Pd-catalyzed hydroxylation of an aryl bromide, and end-game assembly through a Pd-catalyzed C–H activation step. The overall yield could be significantly improved, and the costs could be reduced.",10.1021/acs.oprd.0c00076,2020-07-01,0.7777739333145615
Organic Process Research & Development,Streamlined Processes for the Synthesis of a Farnesyl Transferase Inhibitor Drug Candidate,"As part of a fast-paced oncology program, quinolinone 1 was discovered and developed as a potent inhibitor of farnesyl transferase for the treatment of cancer. The initial synthesis, which suffered from a lengthy linear sequence and a late-stage chromatographic resolution, was deemed not amenable to large-scale production. While investigating alternate routes to address these issues, the original synthesis was successively improved and streamlined. This enabled route supplied the timely production of drug substance required to support early toxicological and clinical studies. Several iterations of the process were made, and as a result of these improvements, an efficient four-step sequence was developed for the synthesis of quinolinone d -tartrate 2 starting from readily available outsourced intermediate 5 in 26% overall yield, including a classical resolution. The key features of the synthesis include a Castro−Stevens coupling, an imidazole Grignard addition, and a concomitant classical resolution/final salt formation with d -(−)-tartaric acid.",10.1021/op049935g,2004-06-26,0.777708964857563
Organic Process Research & Development,Synthesis and Process Optimization of Boceprevir: A Protease Inhibitor Drug,"Efforts toward the synthesis and process optimization of boceprevir 1 are described. Boceprevir synthesis was optimized by telescoping the first three steps and last two steps of the five-step process. Optimization of oxidation, which is one of the critical steps in the total synthesis, is discussed. A control strategy for the three impurities is described. A novel process for the synthesis of fragment A ( 2 ) has been developed, which is the key starting material for the synthesis of boceprevir.",10.1021/op500065t,2014-07-21,0.7764694557153504
Journal of Organic Chemistry,Development of Two Synthetic Routes to a Benzofuran Intermediate for Fruquintinib,"Two practical routes were developed for the synthesis of a key benzofuran intermediate used to prepare fruquintinib, both of which commence from readily available monoprotected resorcinol derivatives. The first route involves constructing a 2-methylbenzofuran-3-carboxylic acid core from 2-bromo-5-methoxyphenol and a 2-butynoic acid derivative using Michael addition chemistry, followed by intramolecular Heck cyclization. Final deprotection afforded the benzofuran intermediate in 45% overall yield over three steps (or in 58% yield over five steps when starting from ethyl 2-butynoate ester) using the same bromide employed in the current industrial route. In contrast, the second route began with significantly less expensive 2-hydroxy-4-methoxybenzaldehyde. Condensation of the aldehyde with acrylonitrile afforded 3-cyano-2 H -chromene, which underwent a base-catalyzed rearrangement to give a benzofuran-3-carbonitrile. Subsequent conversion of the nitrile into the corresponding N -methylamide, followed by demethylation, provided the target intermediate in an improved overall yield of 60% over five steps from more cost-effective starting materials.",10.1021/acs.joc.5c02114,2025-11-21,0.7758690177583732
Organic Process Research & Development,"Development and Practical Synthesis of a Triple Reuptake Inhibitor, (1<i>R</i>,2<i>S</i>)-SIPI 5357","A new chromatography-free synthetic route to triple reuptake inhibitor (1 R,2 S )-SIPI 5357 was developed and demonstrated on a 300-g scale. The key feature of this route is an asymmetric induction reaction, where the (2 S,3 S )-aminoketone 6 was highly stereoselectively reduced to (1 R,2 S,3 S )-amino alcohol 7 . After hydrogenation, chlorination, and cyclization, (1 R,2 S )-SIPI 5357 was prepared in 33% overall yield via seven steps from α-bromo ketone 3 .",10.1021/op300258w,2012-11-02,0.7755732102465489
Organic Letters,Efficient Route to Canagliflozin via Anhydroketopyranose,"The development of an efficient route for the synthesis of Canagliflozin is reported. The anhydroketopyranose intermediate was isolated as a novel intermediate, which was used to prepare Canagliflozin API in high purity.",10.1021/acs.orglett.2c00980,2022-05-06,0.7752505915577758
Organic Process Research & Development,Development of a Large-Scale Route to Glecaprevir: Synthesis of the Macrocycle via Intramolecular Etherification,"Glecaprevir was identified as a potent hepatitis C virus (HCV) protease inhibitor, and a large-scale synthesis was required to support the late-stage clinical trials and subsequent commercial launch. The large-scale synthetic route to glecaprevir required the development of completely new synthetic approaches to the two key structural features: the 18-membered macrocycle 3 and the difluoromethyl-substituted cyclopropyl amino acid 4 . In this first manuscript, we describe the route development for the macrocycle 3; the second manuscript will describe the development of a new synthetic route to the difluoromethyl-substituted cyclopropyl amino acid 4 and the final assembly of glecaprevir. The large-scale synthetic route to the macrocycle employed a unique intramolecular etherification reaction as the key step in the macrocycle synthesis, avoiding the scalability limitations of the ring-closing metathesis (RCM) reaction of the enabling route. The large-scale synthetic route to the macrocycle was successfully used to produce the amount of glecaprevir required to support the late-stage clinical development.",10.1021/acs.oprd.0c00244,2020-07-13,0.7746819535725722
Journal of Organic Chemistry,Asymmetric Synthesis of a Potent HIV-1 Integrase Inhibitor,The development of a practical asymmetric total synthesis of the potent HIV-1 integrase inhibitor 5 is described. Key transformations include construction of the naphthridine core in a highly efficient manner followed by cyclization of the 8-membered ring. Control of the atropisomers of intermediates and final compound 5 is also described.,10.1021/acs.joc.6b01229,2016-07-29,0.7741999699828391
Organic Process Research & Development,Development of a Practical Synthesis of a Farnesyltransferase Inhibitor,"The development of a new and practical synthesis for a farnesyltransferase inhibitor 1 is described. The new route started from 2-nitro-5-cyanotoluene ( 9 ) and afforded desired 1 in eight chemical transformations. The key step involved formation of sulfonamide 13 from a hindered β-hydroxyamine 12 through an in situ protection of the hydroxyl group by forming TMS ether. Ultimately, this new route was successfully demonstrated to generate >10 kg of API in 29% overall yield.",10.1021/acs.oprd.8b00307,2018-10-29,0.7740404508474069
Journal of Organic Chemistry,"Remote Electronic Control in the Regioselective Reduction of Succinimides: A Practical, Scalable Synthesis of EP4 Antagonist MF-310","A practical large-scale chromatography-free synthesis of EP4 antagonist MF-310, a potential new treatment for chronic inflammation, is presented. The synthetic route provided MF-310 as its sodium salt in 10 steps and 17% overall yield from commercially available pyridine dicarboxylate 7. The key features of this sequence include a unique regioselective reduction of succinimide 2 controlled by the electronic properties of a remote pyridine ring, preparation of cyclopropane carboxylic acid 3 via a Corey-Chaykovsky cyclopropanation, and a short synthesis of sulfonamide 5.",10.1021/jo901267x,2009-08-07,0.7734353016604271
Organic Process Research & Development,Development of a Kilogram-Scale Asymmetric Synthesis of a Potent DP Receptor Antagonist,"An efficient asymmetric synthesis of a unique sulfenylated prostaglandin DP receptor antagonist candidate is described. The synthesis is characterized by a novel intramolecular Friedel−Crafts cyclization of an imino-pyrrole to prepare the azaindole core. Other key steps include a highly selective Horner−Wadsworth−Emmons olefination of a tricyclic ketone intermediate and subsequent catalytic asymmetric hydrogenation of a trisubstituted α,β-unsaturated ester to install the chirogenic center. Finally, a new indole sulfenylation protocol was developed to install the aromatic thioether functionality in good yield.",10.1021/op100008m,2010-05-26,0.7729168757000988
Journal of Organic Chemistry,Efficient and Practical Synthesis of (<i>R</i>)-2-Methylpyrrolidine,"An efficient, practical, and high yielding synthesis of (R)-2-methylpyrrolidine is described. The sequence allows for the scalable preparation of the target compound in just four synthetic steps and proceeds in 83% overall yield and >99% optical purity from readily available starting materials.",10.1021/jo060319n,2006-05-01,0.7728755128487266
Organic Process Research & Development,Process Development and Large-Scale Synthesis of a PDE4 Inhibitor,"An efficient, scalable synthesis of the PDE4 inhibitor, 6-[1-methyl-1-(methylsulfonyl)ethyl]-8-(3-{( E )-2-(3-methyl-1,2,4-oxadiazol-5-yl)-2-[4-(methylsulfonyl)phenyl]vinyl}phenyl)quinoline benzenesulfonate ( 10 ) is described. The synthesis is highly convergent, generating the penultimate 9 by coupling aldehyde 7 and oxadiazole 8 in a Knoevenagel reaction. The process consists of a total of nine chemical steps, five of which comprise the sequence to prepare aldehyde 7 via Skraup reaction, bromination, sulfone formation, methylation and Suzuki−Miyaura cross-coupling, and a two-step sequence for the synthesis of oxadiazole 8 that includes the methylamidoxime and oxadiazole steps. The final two steps are Knoevenagel coupling and salt formation. The process produced the drug candidate 10 in 46% overall yield from 2-bromo-4-methylaniline ( 1 ) on multikilogram scale.",10.1021/op050116l,2005-12-07,0.7724864543357031
Organic Process Research & Development,"A One-Pot Asymmetric Synthesis of a <i>N</i>-Acylated 4,5-Dihydropyrazole, A Key Intermediate of Thrombin Inhibitor AZD8165","A short, chromatography-free, and scalable synthetic route to thrombin inhibitor 1, the active metabolite of the propionic ester prodrug AZD8165, has been developed. The key synthetic step involved cycloaddition of TMS–diazomethane and ethyl acrylate to give an intermediate racemic dihydropyrazole which was reacted with enantiomerically pure 4-fluoro mandelic acid chloride in a one-pot dynamic kinetic resolution (DKR) process.",10.1021/op500134e,2014-08-05,0.7723858110590122
Organic Process Research & Development,An Expedient and Multikilogram Synthesis of a Naphthalenoid H<sub>3</sub> Antagonist,"A facile and scaleable synthesis of potent and selective histamine H 3 receptor antagonist 1 is described, starting from commercially available 6-bromo-naphthalene-2-carboxylic acid methyl ester 3a . The key intermediate, 2-(6-bromonaphthalen-2-yl)ethanol 5 was prepared in good yield (78%) and purity (99%) via a one-carbon homologation of 3a . The coupling of 5 with pyridazinone 12 was accomplished effectively by a copper-catalyzed cross-coupling reaction. Activation of the hydroxyl group of 4, followed by displacement reaction with 2( R )-methylpyrrolidine 13, afforded the free base of 1, which was subsequently converted to its corresponding salt. The new process consisted of eight chemical steps and one salt formation step and required no chromatographic purification throughout the synthesis. It has been successfully implemented on pilot plant scale to prepare over 10 kg quantities of the target compound 1 in 43% overall yield in high purity (99%) and with the desired physical properties.",10.1021/op700102k,2007-10-26,0.7721547150624871
Organic Process Research & Development,Development of a Practical and Scalable Synthesis of a Potent p38 Mitogen-Activated Protein Kinase Inhibitor,"Process research and development of a practical and scalable synthetic method toward a potent inhibitor of p38 mitogen-activated protein kinase 1 is described. The medicinal chemistry synthetic method had several issues in scale-up synthesis. In contrast, the synthetic method described here does not require purification by column chromatography for all steps, and the formation of impurities is suppressed well. Aminopyrazole ring formation was achieved by reaction between a new chiral amine building block 7 and bromoketone unit 4 as a key reaction. This highly efficient and scalable process was successfully demonstrated in the large-scale synthesis of 1·HBr .",10.1021/op300237b,2012-10-10,0.7719377509421522
Organic Process Research & Development,"Process Research and Kilogram Synthesis of an Investigational, Potent MEK Inhibitor","TAK-733 ( 1 ) is an investigational, novel MEK kinase inhibitor that bears a 6-fluoropyridopyrimidone core. Process research of 1 was conducted, and an efficient, scalable route was developed. The key intermediate, a multisubstituted fluoropyridone, was formed in one pot via a three-step cascade reaction: condensation between α-fluoromalonate and malononitrile, methyl amide formation, and intramolecular cyclization. Chlorination of the hydroxyl functionality and cyclization with formic acid provided the desired pyridopyrimidone core in high yield. Subsequent N -alkylation with the nosylate of ( R )-glycerol acetonide and displacement of the chlorine with 2-fluoro-4-iodoaniline proceeded successfully with good yields. Final acid-catalyzed deprotection of the acetonide functionality followed by a controlled crystallization protocol afforded the active pharmaceutical ingredient (API) with the desired polymorph. Compared to the initial synthesis, this route was more concise (six steps compared to the original nine steps), and the overall yield was improved significantly (from 3% to 25%). These improvements allowed for production of multikilograms of 1 .",10.1021/op300198a,2012-09-14,0.7715554951289343
Organic Letters,"A Practical, Enantioselective Synthetic Route to a Key Precursor to the Tetracycline Antibiotics","A practical, enantioselective synthetic route to a key precursor to the tetracycline antibiotics is reported. The route proceeds in nine steps (21% yield) from the commercial substance methyl 3-hydroxy-5-isoxazolecarboxylate. Key steps in the route involve enantioselective addition of divinylzinc to 3-benzyloxy-5-isoxazolecarboxaldehyde and an endo-selective intramolecular furan Diels-Alder cycloaddition reaction. The route described has provided more than 40 g of chromatographically pure 1 with 93% ee.",10.1021/ol071377d,2007-08-01,0.7714496892169953
Tetrahedron,Selective synthesis of sulfonylureas and carboxysulfamides a novel route to oxazolidinones.,,10.1016/s0040-4039(00)88103-4,1983-01-01,0.7714161775405661
Organic Process Research & Development,"Scalable Synthesis of CVN424, an Inverse Agonist of the GPR6 Receptor","CVN424 is a drug candidate, which is being investigated in clinical trials for the treatment of motor fluctuations associated with Parkinson’s disease. We herein describe the process development of an efficient synthetic route that delivered several kilograms of the drug substance. The synthesis included diacylation of commercially available 3,4-diaminopyridine 1 with diethyl oxalate to give 2 and chlorination with POCl 3 to give pyrido[3,4- b ]pyrazine 3, followed by two sequential nucleophilic aromatic substitutions. A final hydrogenation and acetylation of intermediate 7 provided CVN424. Overall, a safe and robust synthesis was developed, which occurred in five linear steps with an overall yield of 15%.",10.1021/acs.oprd.2c00181,2023-01-26,0.7713954513342192
Organic Process Research & Development,Development of a Process Route to the FAK/ALK Dual Inhibitor TEV-37440,"The development of a scalable route to TEV-37440, a dual inhibitor of focal adhesion kinase (FAK) and anaplastic lymphoma kinase (ALK), is presented. The medicinal chemistry route used to support this target through nomination is reviewed, along with the early process chemistry route to support IND (inversigational new drug) enabling activities within CMC (Chemistry, Manufacturing, and Controls). The identification and development of an improved route that was performed in the pilot plant to supply early phase clinical supplies are discussed. Details surrounding the use of a novel ring expansion, a selective nitration through a para-blocking group strategy, a single-pot amination–hydrogenation, a diastereomeric salt resolution, a through-process step to avoid a hazardous intermediate, and a practical formation of a trihydrochloride dihydrate salt are disclosed.",10.1021/acs.oprd.7b00070,2017-04-25,0.7713700091293904
Tetrahedron,Mycorrhizin a: A synthesis of tricyclic enones epimeric with and identical with the key synthetic intermediate of koft and smith,,10.1016/s0040-4039(01)81633-6,1984-01-01,0.7709903020110406
Organic Process Research & Development,"A Scalable Process for the Synthesis of 2-Methyl-1,4,5,6-tetrahydroimidazo[4,5-<i>d</i>][1]benzazepine Monohydrate and 4-[(Biphenyl-2-ylcarbonyl)amino]benzoic Acid:  Two New Key Intermediates for the Synthesis of the AVP Antagonist Conivaptan Hydrochloride","A process for the multikilogram synthesis of the dual vasopressin-receptor antagonist, conivaptan hydrochloride, has been developed. This method relies on the introduction of operationally simple chemistry during the final stages of the process when two key intermediates, isolated by crystallization, are reacted to assemble the final molecule. A three-stage sequence has been developed for the synthesis of the first key amine hydrate intermediate, and modifications of the original process are described here. Major strategic improvements have been made in defining the final route to the “side chain” precursor molecule, which is the second key intermediate. These advances revolve around the acylation of an unprotected amino benzoic acid and subsequent high-yield telescoped processes for the synthesis of 4-[(biphenyl-2-ylcarbonyl)amino]benzoic acid. This novel method leads to a 4-fold increase in the overall yield of the target materials, circumvents the restricted synthetic intermediates, and constitutes a safe, reliable, adaptable, environmentally friendly, and cost-effective approach with improved manipulability.",10.1021/op050061n,2005-08-23,0.7706749923596784
Organic Process Research & Development,Selection and Development of a Route for Cholesterol Absorption Inhibitor AZD4121,"The development of a synthetic route to the cholesterol absorption inhibitor AZD4121 is presented. Key steps are a highly enantioselective CBS reduction, a stereospecific Staudinger reaction, an amine/lithium chloride mediated ester hydrolysis, and a resolution of a 50:50 diastereomeric mixture by recrystallization. The synthesis was accomplished in 10 linear steps, and the overall yield, when compared with the lead optimization (LO) route, was improved from 1% to 20%. All purifications of intermediates through preparative HPLC or silica gel chromatography were avoided. This was possible since many of the intermediates along the route could be used as such in the next step until an intermediate with suitable crystalline properties could be identified and purified through crystallization.",10.1021/op200314z,2012-03-20,0.7701565809159484
Journal of Organic Chemistry,A Practical Synthesis of Renin Inhibitor MK-1597 (ACT-178882) via Catalytic Enantioselective Hydrogenation and Epimerization of Piperidine Intermediate,"A practical enantioselective synthesis of renin inhibitor MK-1597 (ACT-178882), a potential new treatment for hypertension, is described. The synthetic route provided MK-1597 in nine steps and 29% overall yield from commercially available p-cresol (7). The key features of this sequence include a catalytic asymmetric hydrogenation of a tetrasubstituted ene-ester, a highly efficient epimerization/saponification sequence of 4 which sets both stereocenters of the molecule, and a short synthesis of amine fragment 2.",10.1021/jo102070e,2011-01-20,0.7697885896063564
Organic Process Research & Development,"Commercial Route Development Toward PF-07265807, an AXL-MER Inhibitor Oncology Candidate","Our route scouting efforts toward finding the most efficient construction of PF-07265807 (ARRY-067) in readiness for process development prior to commercial manufacture are described. ARRY-067 contains the azaindazole (1 H -pyrazolo [3,4- b ]pyridine) building block that is common to many pharmaceuticals and bioactive agents. Herein, our novel approach to this challenging structural motif is described where an oxazoline ring-opening cyclization cascade triggered by the addition of hydrazine reveals the target 3-alaninol-substituted azaindazole in one step. An improved synthesis of the uracil carboxylic acid coupling partner is also described. Overall, the new route is six steps shorter than the enabling route, minimizes protecting group manipulations, and avoids the use of transition metal catalysis.",10.1021/acs.oprd.4c00049,2024-04-16,0.7695845339403212
Organic Process Research & Development,Practical and Scalable Manufacturing Process for a Novel Dual-Acting Serotonergic Antidepressant Vilazodone,"Vilazodone combines the effects of a selective serotonin reuptake inhibitor with the 5-HT 1A receptor partial agonist activity. Here, we report the development of a viable and scalable process for manufacturing vilazodone that features a convergent synthetic approach, with low cost and high purity. The key indole synthesis was improved to first make up the hydrazone intermediate and then modify a pendant hydroxy group to realize a much increased overall yield. This process was successfully used to prepare >2 kg of vilazodone hydrochloride with a total yield of 56.2% and purity of 99.93%.",10.1021/acs.oprd.1c00069,2021-04-22,0.7693579538276941
Organic Process Research & Development,Development of a Scalable Manufacturing Synthesis for Enarodustat,"Enarodustat (brand name Enaroy) is an oral hypoxia-inducible factor prolyl hydroxylase (PHD) inhibitor for the treatment of renal anemia in chronic kidney disease (CKD) patients. Establishing a commercial synthetic route for drug substances is essential for ensuring stable delivery to patients. To overcome challenges associated with the medicinal chemistry route, such as avoiding a cryogenic reaction and column purification, we devised a synthetic route incorporating the dichlorotriazolopyridine derivative 14 as a key intermediate, with the regioselective introduction of a phenethyl group onto it as a key step. This key step was resolved through a nucleophilic substitution employing a malonate derivative. We prepared the key intermediate by improving a known reaction which gave extremely low yields. After thorough investigation, we achieved a kilogram-scale synthesis, successfully overcoming these challenges. The overall yield was 23% in 8 chemical steps, with a purity suitable for human administration.",10.1021/acs.oprd.5c00306,2025-10-23,0.769334424100486
Journal of Organic Chemistry,Practical Syntheses of a CXCR3 Antagonist,"Two new, reliable syntheses of a pyrido[2,3-d]-pyrimidine inhibitor of the CXCR3 receptor are described. A nine-step synthesis of the CXCR3 inhibitor (1) from 2-aminonicotinic acid was demonstrated on a multikilogram scale and incorporates a classic resolution to deliver the enantioenriched active pharmaceutical ingredient (API). A second synthesis of the CXCR3 inhibitor starts from (+)-(D)-Boc alanine and 2-chloronicotinic acid and utilizes a Goldberg coupling. This second synthesis, performed on a gram scale, intersects the former route at a common intermediate thereby completing a formal synthesis of the enantioenriched API in higher overall yield without the need for a resolution.",10.1021/jo102399a,2011-02-07,0.7688271705633349
Organic Process Research & Development,An Efficient and Scalable Synthesis of the Spirocyclic Glycine Transporter Inhibitor GSK2137305,An efficient and scalable synthesis of a glycine transporter inhibitor is presented. The key steps in the synthetic sequence are the formation of a spirocyclic imidazolidinone from an α-amino nitrile and a cyclic ketone and an arylation of 4-methyl imidazole under ‘ligandless’ Ullmann coupling conditions.,10.1021/op100210s,2010-11-10,0.7688116894259658
Tetrahedron,A new synthetic route to macrocycles : Synthesis of large ring enaminolactones,,10.1016/s0040-4039(00)76754-2,1994-03-01,0.7682308217781348
Organic Process Research & Development,Convergent Kilo-Scale Synthesis of a Potent Renin Inhibitor for the Treatment of Hypertension,"Process research and development of a synthetic route towards a novel renin inhibitor ( 1 ) is described. The highly convergent synthetic route provided 1 in 15% yield on multikilogram scale with a longest linear sequence of 11 steps. The use of catalytic hydrogenation features prominently in our design. The proper choice of N -methylpyridone surrogate was also important, and we describe a method for the easy conversion of 2-methoxypyridines to N -methylpyridones using cheap and readily available reagents.",10.1021/op2001063,2011-06-24,0.7673974526637853
Organic Process Research & Development,Development of a Practical Synthesis of ERK Inhibitor GDC-0994,"The process development of a synthetic route to manufacture ERK inhibitor GDC-0994 on multikilogram scale is reported herein. The API was prepared as the corresponding benzenesulfonate salt in 7 steps and 41% overall yield. The synthetic route features a biocatalytic asymmetric ketone reduction, a regioselective pyridone S N 2 reaction, and a safe and scalable tungstate-catalyzed sulfide oxidation. The end-game process involves a telescoped S N Ar/desilylation/benzenesulfonate salt formation sequence. Finally, the development of the API crystallization allowed purging of process-related impurities, obtaining >99.5 A % HPLC and >99% ee of the target molecule.",10.1021/acs.oprd.7b00006,2017-02-23,0.7673471110042819
Organic Process Research & Development,"Process Development and Large-Scale Synthesis of MK-6186, a Non-Nucleoside Reverse Transcriptase Inhibitor for the Treatment of HIV","A new synthetic route has been developed to drug candidate 1, a second-generation NNRTI being developed as a potential treatment of HIV. Regiocontrol in a key alkylation step was achieved by selective N -alkylation of hydrazone 13 . After a deprotection and cyclisation sequence, 1 was isolated in six steps in 35% overall yield from readily available starting materials.",10.1021/op200334x,2012-01-24,0.7669780022796285
Organic Process Research & Development,"Development of a Scalable Process for CI-1034, an Endothelin Antagonist","A concise, convergent multikilogram synthesis of CI-1034 (1 ), a potent endothelin receptor antagonist, is described. A 15-step preparation from commercially available o -vanillin and benzenesulfonyl chloride employs a remarkably robust Suzuki coupling between a boronic acid and an aromatic sulfonate ester as the key synthetic step. A scalable route capable of producing multikilogram quantities of CI-1034 with no chromatographic steps is described in this contribution. Improvements to the process included using a 4-fluorobenzenesulfonate ester as a suitable substitute for the triflate group in the Suzuki reaction and the use of MgCl 2 as a substitute for TiCl 4 in a Dieckmann condensation to provide the benzothiazine dioxide core.",10.1021/op034104g,2004-03-01,0.7669462940193762
Organic Process Research & Development,"Development of a Scalable and Practical Synthesis of AB928, a Dual A<sub>2a</sub>/A<sub>2b</sub> Receptor Antagonist","AB928 is a potent and selective dual antagonist of the A 2a and A 2b receptors, which is currently in clinical trials. Here, we report the development of two scalable and practical syntheses of AB928. The first-generation synthesis was used to successfully obtain AB928 in excellent yield and purity to support our preclinical and initial clinical studies. Recently, we have developed a second-generation synthesis of AB928 featuring a palladium-free protocol to access 3-(2-amino-6-chloropyrimidin-4-yl)-2-methylbenzonitrile, a key intermediate in the AB928 synthesis. The new method is scalable, practical, and significantly more cost-effective.",10.1021/acs.oprd.0c00124,2020-06-01,0.7667682158507367
Tetrahedron,"A convergent route to β-hydroxy δ-lactones through Prins cyclisation as the key step: synthesis of (+)-prelactones B, C and V",,10.1016/j.tetlet.2005.01.121,2005-02-15,0.76673892044486
Synthesis,Synthesis of a 5-Spirocyclopropyl Deoxyrhamnojirimycin as a Constrained Naringinase Inhibitor,International audience,10.1055/s-2007-990858,2007-11-01,0.766626686349876
Tetrahedron,The synthesis of a 3-diazobicyclo[2.2.1]Heptan-2-one inhibitor of thromboxane a2 synthetase,,10.1016/s0040-4039(01)80062-9,1984-01-01,0.766626686349876
Tetrahedron,Synthesis of an ecdysteroid inhibitor of ecdysone biosynthesis,,10.1016/s0040-4039(00)93458-0,1991-09-01,0.766626686349876
Tetrahedron,"Synthesis of arnebinol, an inhibitor of prostaglandin biosynthesis",,10.1016/s0040-4039(01)80108-8,1984-01-01,0.766626686349876
Tetrahedron,"Synthesis of myo-inositol 1,4,5-trisphosphate 3-phosphorothioate as an inhibitor of myo-inositol 1,3,4,5-tetrakisphosphate 3-phosphatase",,10.1016/s0040-4039(00)76770-0,1994-03-01,0.766626686349876
European Journal of Organic Chemistry,The First Total Synthesis of Racemic Chebulic Acid,"Abstract The first total synthesis of racemic chebulic acid is reported, which is the aglycon of several antioxidant ingredients of the fruit of the Terminalia chebula tree. The route started with the straightforward preparation of an indanone‐based β‐oxoester from a benzaldehyde derivative (84 % over the first five steps). The side chain of the target compound was then introduced by conjugated addition of a cuprate reagent derived from dimethyl succinate, which was followed by the first key step of the synthesis: a cerium‐catalyzed α‐hydroxylation of an β‐oxoester. The second key step was the cyanide‐catalyzed ring transformation of the cyclic α‐hydroxy‐β‐oxoester to a δ‐lactone. Finally, chebulic acid was obtained after six‐fold demethylation of three methyl ester moieties and three phenolic ether functions. The overall synthetic route consists of nine consecutive steps and was accomplished in 15 % overall yield.",10.1002/ejoc.202101508,2021-12-22,0.7662544002339868
Organic Process Research & Development,"Process Research on a Phenoxybutyric Acid LTB4 Receptor Antagonist. Efficient Kilogram-Scale Synthesis of a 3,5-Bisarylphenol Core","An improved, kilogram-scale synthesis of a LTB4 receptor antagonist is reported. The title compound was prepared in four linear steps (seven steps total) and 54% overall yield. The 3,5-bisarylphenol core was obtained in nearly quantitative yield by the condensation of 1-benzotriazol-1-ylpropan-2-one with a chalcone. Although all the intermediates were oils, no chromatography purification was required.",10.1021/op300302s,2012-11-30,0.7660870638946531
Organic Process Research & Development,The First Large-Scale Synthesis of MK-4305: A Dual Orexin Receptor Antagonist for the Treatment of Sleep Disorder,"A new synthetic route to drug candidate 1, a potent and selective dual orexin antagonist for the treatment of sleep disorders, has been developed. The key acyclic precursor 10 was prepared in a one-step process in 75% isolated yield from commercially available starting materials using novel chemistry to synthesize 2-substituted benzoxazoles. A reductive amination was followed by a classical resolution to afford chiral diazepane ( R )- 11 . Finally, coupling of ( R )- 11 with acid 5 furnished the desired drug candidate 1 .",10.1021/op1002853,2011-03-04,0.765934134907905
Synthesis,"Efficient Synthesis of 4-(3-Fluoro-5-{[4-(2-methyl-1<i>H</i>-imidazol-1-yl)benzyl]oxy}phenyl)tetrahydro-2<i>H</i>-pyran-4-carboxamide, a Novel 5-Lipoxygenase Inhibitor","An efficient synthesis of 1, a novel orally active 5-lipoxygenase inhibitor, was developed. Key features of the modified synthetic route include facile construction of the benzyl phenyl ether moiety by nucleophilic aromatic substitution and THP ring by cyclization, and base-promoted hydrolysis of the nitrile group to carboxamide. The improved three-step synthesis provides 25 g of 1 for pre-clinical toxicology studies in a total yield of 59%.",10.1055/s-2004-831227,2004-01-01,0.765498631347287
Organic Process Research & Development,Efficient Stereoselective Synthesis of a Key Chiral Aldehyde Intermediate in the Synthesis of Picolinamide Fungicides,"A highly stereoselective and efficient synthesis of (4 S,5 S,6 S )-6-(benzyloxy)-5-phenoxy-4-propoxyheptanal, a key intermediate for syntheses of picolinamide fungicides, is described in this report. The synthesis features a scalable allylpropyl ether preparation, an efficient synthesis of the C1–C3 anti, syn -( S, S, S ) stereotriad via a highly diastereoselective allylboration, and Cu-catalyzed phenylation of a sterically hindered secondary alcohol with BiPh 3 (OAc) 2 followed by highly regioselective hydroformylation with the formation of a linear aldehyde. Excellent overall route efficiency was achieved (six steps and 39% yield) starting from readily available and inexpensive ( S )-ethyl lactate.",10.1021/acs.oprd.9b00310,2019-09-19,0.7649594189080292
Organic Process Research & Development,"Development of a Safe, Efficient, and Scalable Process for the Synthesis of Midazolam Hydrochloride","We describe the development of a concise large-scale process for the synthesis of midazolam hydrochloride. The key processes include a novel one-pot reductive amination–deprotection–cyclization process between 2-aminobenzophenone and Boc-protected 1,3-diaminopropan-2-one, followed by an intermolecular cyclization and oxidative dehydrogenation reaction. Three routes were developed and optimized, and the third-generation process was chosen as the best one, which delivered midazolam hydrochloride with an overall yield of up to 26.5% and purity of 99.8% by four distinct intermediates and a salt-formation step. The quality of the target molecule fully complies with all pertinent ICH criteria. Compared to the literature routes, the total steps, overall yield, and process security have all been significantly improved.",10.1021/acs.oprd.3c00327,2023-11-29,0.7649493763484088
Journal of Organic Chemistry,Nitrone [2+3]-Cycloadditions in Stereocontrolled Synthesis of a Potent Proteasome Inhibitor:  (−)-Omuralide,"A new stereocontrolled synthetic route to omuralide has been developed from methyl pyroglutamate. This route involves regio- and stereoselective N-methylnitrone 1,3-dipolar cycloadditions to appropriate pyrrolinones, beta-eliminations, and highly selective hydrogenations as the main steps.",10.1021/jo701968d,2007-11-29,0.7646282949785933
Tetrahedron,Enantioselective synthesis of a key tricyclic intermediateen route to (+)-gelsemine,,10.1016/s0040-4039(99)01132-6,1999-08-01,0.7645606174098067
Organic Process Research & Development,Development of an Enabling Route to PF-00610355: A Novel Inhaled β<sub>2</sub>-Adrenoreceptor Agonist,"The initial route used to prepare PF-00610355 ( 8 ) for early clinical development is described. Through careful choice of solvent, an efficient, telescoped route to carboxylic acid 23 was developed, affording this late-stage intermediate in 80% yield over 4 steps. Deprotection of 23 to give sodium salt 24a and coupling with amine 6 ·HCl afforded the desired API. Effective synthetic routes to two of the starting materials, chiral bromide 1 and amine 6, are also described.",10.1021/op2001904,2011-08-24,0.7640374405577122
Tetrahedron,"A novel three-step synthetic route to 1,4-anthraquinones",,10.1016/0040-4039(94)88098-0,1994-08-01,0.7640257683911655
Organic Process Research & Development,Development of a New Synthetic Route of the Key Intermediate of Irbesartan,"Herein, we describe a new synthetic route to prepare 4′-((2-butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl)-[1,1′-biphenyl]-2-carbonitrile ( 5 ), an intermediate of irbesartan. Compared with leucine or its derivatives as the starting material to synthesize irbesartan in many previous reports, the intermediate 5 could be obtained in four steps from low-cost and commercially available glycine methyl ester as the starting material, which also avoided the use of highly toxic cyanide. The spirocycle structure in the intermediate 5 was constructed with dihaloalkanes via a simple alkylation reaction. The related impurities and process parameters were studied in detail. Finally, the scale-up of this route was successfully performed on a 200 g scale, affording 332 g of the intermediate 5 with 98.4% purity and 54.2% overall yield in four steps. Meanwhile, process mass intensity and yield stability were demonstrated. The current synthetic route provides an alternative strategy for the production of irbesartan.",10.1021/acs.oprd.2c00113,2022-08-04,0.7639479078796431
Organic Process Research & Development,Enantioselective Synthesis of a Highly Substituted Tetrahydrofluorene Derivative as a Potent and Selective Estrogen Receptor Beta Agonist,"The development and execution of a practical asymmetric synthesis of the estrogen receptor beta selective agonist (8 R,10a S )-6-(trifluoromethyl)-8,9,10,11-tetrahydro-8,10a-methanocyclohepta[1,2]indeno[4,5- d ][1,2,3]triazol-7(3 H )-one is described. The optimized route features a key chiral auxiliary-mediated dialkylation approach to set the all-carbon quaternary center with exceptional stereocontrol. Overall, the chemistry has been used to prepare >30 kg of drug candidate in 21% overall yield through 13 longest linear steps and with >99% ee.",10.1021/op5000489,2014-03-03,0.7628869835373577
Organic Process Research & Development,Process Development and Scale-Up of an Hsp90 Inhibitor,A scalable process for the manufacture of a Hsp90 inhibitor was developed and optimized. Key features in the seven-step process include a selective S N Ar reaction followed by an Ullmann-type coupling of indazolone to an aryl halide. This improved process afforded 65% yield over two critical steps compared to 25% following the Medicinal Chemistry route.,10.1021/op300262z,2012-10-24,0.7626003598963439
Organic Process Research & Development,"Synthesis of the NK1 Receptor Antagonist GW597599. Part 3: Development of a Scalable Route to a Key Chirally Pure Arylpiperazine Urea, A Happy End","GW597599 1 is a novel NK-1 antagonist currently under investigation for the treatment of central nervous system disorders and emesis. The initial chemical development synthetic route, derived from the one used by medicinal chemistry, involved several hazardous reagents, gave low yields and produced high levels of waste. Through a targeted process of research and development, application of novel techniques and extensive route scouting, a new synthetic route for GW597599 was developed. This paper reports the optimisation work of the third and last stage in the chemical synthesis of GW597599 and the development of a pilot-plant-suitable process for the manufacturing of optically pure arylpiperazine derivative 1 . In particular, the process eliminated the use of triphosgene in the synthesis of an intermediate carbamoyl chloride, substantially enhancing safety, overall yield, and throughput.",10.1021/op9002032,2009-10-02,0.7619524684730176
Organic Process Research & Development,Asymmetric Synthesis of a Glucagon Receptor Antagonist via Friedel–Crafts Alkylation of Indole with Chiral α-Phenyl Benzyl Cation,"Development of a practical asymmetric synthesis of a glucagon receptor antagonist drug candidate for the treatment of type 2 diabetes is described. The antagonist consists of a 1,1,2,2-tetrasubstituted ethane core substituted with a propyl and three aryl groups including a fluoro-indole. The key steps to construct the ethane core and the two stereogenic centers involved a ketone arylation, an asymmetric hydrogenation via dynamic kinetic resolution, and an anti -selective Friedel–Crafts alkylation of a fluoro-indole with a chiral α-phenyl benzyl cation. We also developed two new efficient syntheses of the fluoro-indole, including an unusual Larock-type indole synthesis and a Sugasawa-heteroannulation route. The described convergent synthesis was used to prepare drug substance in 52% overall yield and 99% ee on multikilogram scales.",10.1021/op300249q,2012-10-15,0.7619490871983534
Organic Process Research & Development,Development of a Scalable Asymmetric Process for the Synthesis of GLYT1 Inhibitor BI 425809 (Iclepertin),"A robust and scalable synthesis process for BI 425809 ( Iclepertin ), a GLYT1 inhibitor with potential therapeutic properties for the treatment of central nervous system disorders, was developed and implemented on a multikilogram scale. Key aspects of the process include the efficient asymmetric synthesis of intermediate 3-((1 R,5 R )-3-azabicyclo[3.1.0]hexan-1-yl)-5-(trifluoromethyl)isoxazole·HCl from raw materials readily available in bulk and the synthesis of ( R )-5-(methylsulfonyl)-2-((1,1,1-trifluoropropan-2-yl)oxy)benzoic acid through a novel Rh-catalyzed asymmetric hydrogenation.",10.1021/acs.oprd.2c00373,2023-03-03,0.7615013969296129
Tetrahedron,Efficient synthesis of the selective COX-2 inhibitor GW406381X,,10.1016/j.tetlet.2006.12.045,2007-01-05,0.7613963178592971
Organic Process Research & Development,An Alternative Scalable Process for the Synthesis of the Key Intermediate of Omarigliptin,"An alternative scalable process for the synthesis of the key intermediate of omarigliptin is described. The asymmetric synthesis relies on the initial diastereoselective alkylation and subsequent aluminum-catalyzed substrate-controlled Meerwein–Ponndorf–Verley reduction. A highly regioselective 5-exo-dig iodocyclization followed to afford 11b, which was then subjected to ring-opening cycloetherification to give product 1 with >99:1 dr and >99% ee in 31.2% overall yield in nine steps. This synthetic strategy has been successfully applied for multikilogram scale production.",10.1021/acs.oprd.6b00295,2016-11-23,0.7613292943894525
Organic Process Research & Development,Kilogram-Scale Synthesis of the CXCR4 Antagonist GSK812397,"An improved, scalable synthesis of the CXCR4 antagonist GSK812397 is described. This new route was recently scaled up in 50 L fixed equipment to afford 1.2 kg of drug substance in five steps with an overall yield of 20% and >99% chemical and enantiomeric purity.",10.1021/op9000675,2009-05-07,0.7612672989323822
Organic Process Research & Development,Practical Large-Scale Synthesis of Endothelin Receptor Antagonist S-0139,Semisynthetic endothelin receptor antagonist S-0139 was synthesized in 14 steps from oleanolic acid 2 in a 20% overall yield on a multi-kilogram scale. Our previous synthesis of the oleanane skeleton was modified and improved to give phosphonate 9 as a key intermediate. The side chain on the 27-position was introduced by Horner−Wadsworth−Emmons olefination of phosphonate 9 with aldehyde 5 . Aldehyde 5 was prepared in a one-pot reduction−acylation process starting from 5-hydroxy-2-nitrobenzaldehyde. The entire sequence of the synthesis can be done without chromatography and yields S-0139 of high purity.,10.1021/op990036f,1999-08-05,0.7610782452401273
Synthesis,A New Route to Roflumilast via Copper-Catalyzed Hydroxylation,"A new route to Roflumilast, a selective phosphodiesterase type 4 (PDE 4) inhibitor, is described. The synthetic procedure starts from 4-hydroxy-3-iodobenzoic acid to access the key intermediate 3-(cyclopropylmethoxy)-4-(difluoromethoxy)benzoic acid via copper-catalyzed hydroxylation and utilizes amide coupling to accomplish the synthesis of Roflumilast in 80% overall yield.",10.1055/s-0032-1317527,2012-11-06,0.7606202908190626
Tetrahedron,An efficient synthetic route for quinazolinyl 4-thiazolidinones,,10.1016/j.tetlet.2009.06.086,2009-06-22,0.7599596992610391
Journal of Organic Chemistry,A Practical Synthesis of 5-Lipoxygenase Inhibitor MK-0633,"Practical, chromatography-free syntheses of 5-lipoxygenase inhibitor MK-0633 p-toluenesulfonate (1) are described. The first route used an asymmetric zincate addition to ethyl 2,2,2-trifluoropyruvate followed by 1,3,4-oxadiazole formation and reductive amination as key steps. An improved second route features an inexpensive diastereomeric salt resolution of vinyl hydroxy-acid 22 followed by a robust end-game featuring a through-process hydrazide acylation/1,3,4-oxadiazole ring closure/salt formation sequence to afford MK-0633 p-toluenesulfonate (1).",10.1021/jo100561u,2010-05-20,0.759577834887535
Organic Process Research & Development,An Efficient Multikilogram Synthesis of ABT-963:  A Selective COX-2 Inhibitor,"An efficient chemical process for the multikilogram synthesis of ABT-963 ( 3 ) is described. The potent and selective COX-2 inhibitor was prepared in four steps in 36% overall isolated yield from commercially available 3,4-difluoroaniline ( 4 ). The chemistry, which required no chromatography, involved a facile one-pot synthesis of the pyridazinone core, a selective alkoxylation, a high yielding Suzuki coupling, and a very efficient oxidation.",10.1021/op060016v,2006-04-18,0.7594975319497757
Organic Process Research & Development,Process Development for the Synthesis of a Selective M<sub>1</sub>and M<sub>4</sub>Muscarinic Acetylcholine Receptors Agonist,"A practical and chromatography-free synthetic process to selective M 1 and M 4 muscarinic acetylcholine receptors agonist was developed and demonstrated on a several hundred gram scale. The key feature of this route is N,N -dimethylcarbamoylation of the anilinic nitrogen on the spiro 7-azaindoline structure via intermolecular migration of the N,N -dimethylcarbamoyl group. The resulting compound 1 was prepared in 43% overall yield with a chemical purity >99% via six steps starting with (2-chloropyridin-3-yl)acetonitrile.",10.1021/acs.oprd.7b00236,2017-09-05,0.7594573632503869
Organic Process Research & Development,"Process Development and Scale-Up for the Preparation of the 1-Methyl-quinazoline-2,4-dione Wnt Inhibitor SEN461","A practical and scalable route to the Wnt inhibitor SEN461 1 is described herein. The optimized route consists of nine chemical steps. The intermediates are solids and were isolated by filtrations. Critical reactions steps in the medicinal chemistry route were modified for an initial scale-up process, and as a result, we developed a synthetic procedure for the preparation of multihundred gram quantities of the final product. A further process development for the phase 1 clinical batch campaign is reported.",10.1021/op400145w,2013-07-23,0.7590529925515783
Tetrahedron,"A simple route to methyl 5S-(benzoyloxy)-6-oxohexanoate, a key intermediate in leukotriene synthesis",,10.1016/s0040-4039(00)89063-2,1990-01-01,0.758718262764921
Organic Process Research & Development,Expeditious Synthesis of a Potent Allosteric HIV-1 Integrase Inhibitor GSK3839919A,"A new synthesis of allosteric HIV-1 integrase inhibitor GSK3839919A is described. Key to the efficiency was the synthesis of ( S )-2-(5-bromo-4-(4,4-dimethylpiperidin-1-yl)-2-methylpyridin-3-yl)-2-( tert -butoxy)acetate in only 5 steps compared to 13 steps in the original synthesis. This advanced building block has been used in the syntheses of many drug candidates targeting allosteric HIV integrases. Process development leading to the efficient multi-kilogram synthesis of GSK3839919A is also described, including the optimization of two Pd-catalyzed reactions and isolation of the active pharmaceutical ingredient without salt formation and use of lyophilization and gentisic acid as in the original synthesis.",10.1021/acs.oprd.2c00343,2023-01-09,0.7581423707869461
Organic Process Research & Development,Development of a Scalable Synthesis to VEGFR Inhibitor AG-28262,"The synthesis of N,2-dimethyl-6-(2-(1-methyl-1 H -imidazol-2-yl)thieno[3,2- b ]pyridin-7-yloxy)benzo[ b ]thiophene-3-carboxamide ( 1, AG-28262) on kilogram scale is described. Initial syntheses of key components 2 and 3 worked well on laboratory scale but had significant drawbacks for larger-scale manufacture. Therefore, new routes to these two key fragments were developed and demonstrated to synthesize kilogram quantities. Key steps involve a two-step thiophenol alkylation/cyclization protocol to synthesize 2 in a convergent manner. A difficult Pd-mediated coupling to produce 3 was replaced with a more scalable stepwise imidazole synthesis. Key rationale for the new routes are discussed.",10.1021/op0502396,2006-02-10,0.7580364965979605
Tetrahedron,Enantioselective route to a key intermediate in the total synthesis of ginkgolide B,,10.1016/0040-4039(88)85121-9,1988-01-01,0.7579894358415101
Tetrahedron,Enantioselective route to a key intermediate in the total synthesis of forskolin,,10.1016/s0040-4039(00)82359-x,1988-01-01,0.7579894358415101
Organic Process Research & Development,Development of a Scalable Route to a Pyrrolidone Compound via a Hydroxyfuranone,"Herein, we describe the preparation of pyrrolidone compound 1 as a potential antiepileptic drug. The key steps of this synthetic route are based on the preparation of a heterocyclic amine and its condensation with a hydroxyfuranone in a three-step one-pot process. The development of the synthesis led to decreased route complexity and removal of chromatographic purifications. These improvements were demonstrated at scale by the production of 700 g of this pyrrolidone.",10.1021/acs.oprd.1c00350,2022-03-15,0.7577154148224007
European Journal of Organic Chemistry,Synthesis of the <i>N</i>‐Amykitanosyl Tetramic Acid Moiety of Amycolamicin,"Abstract An improved five‐step synthetic route from l ‐fucose to an N ‐glycosyl l ‐valine methyl ester has been developed. The new route involves glycosidation of l ‐fucose with phenol in a β‐selective manner without protection/deprotection steps and one‐pot stereochemical inversion of a secondary alcohol intermediate and is superior to our previous one both in the number of steps and in overall yield. An N ‐glycosyl l ‐valine benzyl ester, prepared from l ‐fucose in an analogous way, has been elaborated into an N ‐amykitanosyl tetramic acid derivative, Li's synthetic intermediate for amycolamicin, via a four‐step sequence which features the utilization of Bestmann's ylide to stereoconvergently construct an N ‐glycosyl tetramic acid intermediate in a single step, opening of a cyclic carbonate ring with an amine to regioselectively install a carbamate functionality, and visible light‐mediated oxidative debenzylation of an N , N ‐dibenzyl carbamate.",10.1002/ejoc.202300075,2023-03-09,0.7574628470625905
Organic Process Research & Development,Synthesis of Mavatrep: A Potent Antagonist of Transient Receptor Potential Vanilloid-1,"The process development of Mavatrep ( 1 ), a potent transient receptor potential vanilloid-1 (TRPV1) antagonist, is described. The two key synthetic transformations are the synthesis of ( E )-6-bromo-2-(4-(trifluoromethyl)styryl)1 H -benzo[ d ]imidazole ( 4 ) and the Suzuki coupling of 4 with 3,3-dimethyl-3 H -benzo[ c ][1,2]oxaborol-1-ol ( 5 ). Compound 1a was prepared in four chemical steps in 63% overall yield.",10.1021/acs.oprd.5b00271,2015-10-02,0.757003714368481
Tetrahedron,Synthesis of /±/-yohimbine and /±/-β-yohimbine. A new route to yohimban ring system.,,10.1016/s0040-4039(00)90106-0,1965-01-01,0.7568981026191699
Tetrahedron,An expeditious synthesis of a 1β-methylcarbapenem key intermediate,,10.1016/0040-4039(88)80016-9,1988-01-01,0.7560797260108618
Organic Process Research & Development,Development and Scale-Up of a Manufacturing Route for the Non-nucleoside Reverse Transcriptase Inhibitor GSK2248761A (IDX-899): Synthesis of an Advanced Key Chiral Intermediate,"A new and improved synthetic route to an intermediate in the synthesis of the phosphinate ester GSK2248761A is described. In the key step, we describe the first process-scale example of a palladium-catalyzed phosphorus–carbon coupling to give the entire backbone of GSK2248761A in one telescoped stage in 65% average yield on a 68 kg scale. This unusual chemistry enabled the route to be reduced from six chemistry stages to four and eliminated a number of environmentally unfriendly reagents and solvents.",10.1021/acs.oprd.7b00356,2018-01-25,0.7560708457584493
Organic Process Research & Development,"An Expedient Approach for the Synthesis of TAM and MET Receptor Kinase Inhibitor’s Core (<i>R</i>)-2-((4-(4-Amino-2-fluorophenoxy)-1-(4-methoxybenzyl)-1<i>H</i>-pyrazolo[3,4-<i>b</i>]pyridin-3-yl)amino)propan-1-ol","A scalable synthetic route to the kinase inhibitor's core ( R )-2-((4-(4-amino-2-fluorophenoxy)-1-(4-methoxybenzyl)-1 H -pyrazolo[3,4- b ]pyridin-3-yl)amino)propan-1-ol targeting TAM and MET kinases is presented. A selective nucleophilic aromatic substitution (S N Ar) reaction was developed as the key transformation along with a Cu-catalyzed C–N coupling reaction. This route comprises fewer steps (four steps) compared to the six-step sequence previously reported in the literature, delivering significantly improved overall yield.",10.1021/acs.oprd.5c00219,2025-08-04,0.7557444918091519
Organic Process Research & Development,"Development of a Scalable Synthetic Route towards a Thrombin Inhibitor, LB30057","Described is a scalable synthetic route towards LB30057 ( 1 ) which is based upon a chiron approach using methyl tyrosinate hydrochloride as a starting material. In situ protection of methyl tyrosinate to its N,O -bis-trimethylsilyl derivative and subsequent N -selective introduction of naphthalenesulfonyl group provided methyl N -2-naphthalenesulfonyltyrosinate ( 9 ). After the phenol group of 9 was triflated to 10, nickel-catalyzed cyanation provided 11 in good yield. The acid chloride 11a was generated via hydrolysis of the ester group followed by the treatment with SOCl 2, and then coupled with cyclopentylmethylamine to give the amide 15 . Imidate formation followed by amidrazone generation and final salt formation with maleic acid afforded 1 .",10.1021/op060083p,2006-08-10,0.7556648926045408
Journal of Organic Chemistry,Practical Synthesis of a Potent Bradykinin B<sub>1</sub>Antagonist via Enantioselective Hydrogenation of a Pyridyl<i>N</i>-Acyl Enamide,"A practical and efficient synthesis of bradykinin B(1) antagonist 1 is described. A convergent strategy was utilized which involved synthesis of three fragments: 3, 6, and 7. Cross coupling of fragments 6 and 7 followed by amidation with 3 enabled efficient synthesis of 1 in 19 steps total, a 35% overall yield from commercially available pyridine 10. The key to the success of the synthesis was the development of a fluorodenitration step to install the fluorine in pyridine 7 and a catalytic enantioselective hydrogenation of N-acyl enamide 9 to set the stereochemistry.",10.1021/jo802772d,2009-05-20,0.7555689431125474
Organic Process Research & Development,Alternative Approach to the Large-Scale Synthesis of the Densely Functionalized Pyrrolidone BMT-415200,"The development of a multi-kilogram-scale synthetic route to enantiomerically pure ((2 S,3 S,4 S )-3-ethyl-4-fluoro-5-oxopyrrolidin-2-yl)methyl methanesulfonate (BMT-415200) 1 is described in this work. In this sequence, a safe and robust process of nine linear steps with four isolations was implemented. The synthesis features highly diastereoselective hydrogenation of enones 12, diastereoselective reduction of ketone 13, and deoxyfluorination of the corresponding secondary alcohol 8 followed by C–H oxidation of 9 to lactam 10 . The target compound 1 was prepared in 19% overall yield with >99% purity from commercially available di- tert -butyl ( S )-4-oxopyrrolidine-1,2-dicarboxylate 7 .",10.1021/acs.oprd.3c00007,2023-03-22,0.7553235979288835
Synthesis,Haworth Synthesis as a Route to the Anthracene Ring System,,10.1055/s-1974-23453,1974-01-01,0.7549382545979255
Organic Process Research & Development,Process Research and Development for the Kilogram Manufacture of the SRC Kinase Inhibitor AZD0530,"Process research and development of a synthetic route towards a novel SRC kinase inhibitor is described. The Medicinal Chemistry route was very long and suffered from extensive use of chlorinated solvents and chromatography. A number of steps in the Medicinal Chemistry route were also unattractive for large-scale use for a variety of reasons. The route was modified to produce a shorter synthetic scheme that started from more readily available materials. By using the modified route, the title compound was manufactured on kilogram scale without recourse to chromatography and in significantly fewer steps. The scaled synthesis required two Mitsunobu couplings, which were developed and scaled successfully. An interesting hydrazine impurity was identified in the second Mitsunobu coupling; a mechanism for its formation is proposed, and a method for its control is described. The formation and control of some other interesting impurities are also described.",10.1021/op100161y,2010-08-23,0.754848085170534
Tetrahedron,"Practical synthesis of Vistusertib (AZD2014), an ATP competitive mTOR inhibitor",,10.1016/j.tetlet.2019.151333,2019-11-05,0.7547546189676606
Organic Process Research & Development,The Synthesis of a Dopamine D<sub>2</sub> Partial Agonist for the Treatment of Schizophrenia,"The synthesis of the phosphoric acid salt of dopamine D 2 partial agonist 2-{4-[4-(7-fluoro-naphthalen-1-yl)-piperazin-1-yl]-butoxy}-5,6,7,9-tetrahydro-1,7,9-triaza-benzocyclohepten-8-one ( 1 ) is reported. The most prominent feature of the molecule is a seven-membered ring urea functionality that has been prepared via an efficient one-pot, three-step transformation. The original synthesis from the Medicinal Chemistry group provided precursor 13 in 10 steps and 2% overall yield, required four chromatographies and employed unsafe reagents such as 2-iodoxybenzoic acid (IBX) and HClO 4 . The optimized synthetic route for the preparation of phosphate salt 1 consists of 12 linear steps with a 10% overall yield. Safer and more robust reaction conditions have been developed with only one required chromatography. Another key step in the synthesis is the coupling of iodide 25 with naphthalenopiperazine 12 to provide 13 . Due to the difficulty to purify this intermediate, a protocol had to be developed to obtain crude material with the required purity, suitable for use in the subsequent salt formation step. Finally, considerable work was carried out to determine the most stable polymorph of the API. As a result, a robust set of conditions has been developed for the formation of phosphoric acid salt 1, providing the desired polymorph in excellent yield and purity.",10.1021/op800307k,2009-03-23,0.7547209041423903
Organic Process Research & Development,Development of a Convergent and Scalable Synthetic Route to Long-Acting RSV Inhibitor JNJ-7950,"JNJ-7950 is a potent small-molecule respiratory syncytial virus (RSV) inhibitor with a long-acting profile in preclinical species. The design and development of a convergent synthetic route accelerated the discovery and development of JNJ-7950. First, the new synthetic route supported the lead candidate (JNJ-7950) selection process and later was adapted to provide a large-scale clinical batch. A shorter and cost-effective synthetic route to the key spiro-azetidine moiety exploited an intramolecular copper-catalyzed C–N coupling. The development of an efficient and sustainable process for telescoping three steps in a single solvent provided the benzimidazole moiety with an 85% overall yield. The spiro-azetidine and the benzimidazole moieties were coupled to provide JNJ-7950 in 48% overall yield with excellent purity over the six longest linear steps. Two GMP batches (6 and 12 kg) of JNJ-7950 were manufactured in parenteral grade quality to support long-acting injectable formulation development and early clinical need.",10.1021/acs.oprd.4c00437,2025-03-27,0.7544418242155532
Organic Letters,Efficient Synthesis of Ningalin C,[reaction: see text] A concise and efficient synthesis of the permethyl derivative of the marine alkaloid ningalin C (2) has been accomplished. The key step involves the formation of a pyrrolinone from an aminoquinone in one pot. An efficient route for the synthesis of the key aminoquinone has also been developed.,10.1021/ol026074s,2002-07-18,0.7540459256466601
Organic Process Research & Development,"A New and Efficient Synthesis of 6-[(5<i>S</i>,9<i>R</i>)-9-(4-Cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]non-7-yl]nicotinic Acid, a Potent LFA-1/ICAM Inhibitor","An efficient synthesis of 6-[(5 S,9 R )-9-(4-cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]non-7-yl]nicotinic acid 1 is described. This new process involves an in situ protection of 6-chloronicotinic acid as trimethylsilyl ester followed by coupling with spirocyclic hydantoin core 2 to give the target product in 89% overall yield after one-pot deprotection and final API recrystallization.",10.1021/op100104z,2010-06-14,0.7539921014781602
Tetrahedron,Es route to polyene macrolide total synthesis; The key chiral segments of roflamycoin,,10.1016/s0040-4039(00)85073-x,1986-01-01,0.7538834929615088
Organic Process Research & Development,Development of an Efficient New Route to PPARδ Agonist Fonadelpar: Formation of the C–C Bond by Claisen Condensation,"An efficient new synthesis of a peroxisome proliferator-activated receptor delta agonist fonadelpar was developed. The new process features a more practical approach to construct the ethylene linker of fonadelpar by coupling an advanced aldehyde and a ketone via Claisen–Schmidt condensation, which is followed by hydrogenation and an optimized process to obtain the isoxazole moiety. The convergent synthesis provides a robust and scalable approach to prepare the drug candidate in significantly fewer steps and with a higher yield.",10.1021/acs.oprd.2c00235,2022-09-23,0.7537208150491559
Organic Process Research & Development,Practical Manufacturing Process for Baloxavir Marboxil: Efficient Route to a Tricyclic Triazinanone Scaffold,"Baloxavir marboxil, a cap-dependent endonuclease inhibitor, is an antiviral drug for influenza. This paper presents the development of two alternative routes for the industry-oriented preparation of a key tricyclic triazinanone intermediate, 7-(benzyloxy)-3,4,12,12a-tetrahydro-1 H -[1,4]oxazino[3,4- c ]pyrido[2,1- f ][1,2,4]triazine-6,8-dione, in order to overcome the drawbacks of the initial scaled-up synthetic route used in the kilo lab. The first candidate route is based on a late-stage reductive approach to the target starting with raw materials used in the previous route, namely, morpholin-3-one and a pyridone carboxylic acid derivative. The highlight of this approach is the tandem condensation of the morpholine and pyridone units to construct the tricyclic core of the substrate for the final reduction step. The other candidate route engages less expensive raw materials, combination of a protected 2-aminoethanol and 2-bromo-1,1-dimethoxyethane instead of morpholin-3-one, and six chemical steps in total. The efficient transformation was accomplished by a single-step conversion consisting of four elementary steps, including tandem cyclizations accompanied by deprotections. The latter process proved to be robust for production of more than tens of kilograms for practical large-scale manufacturing, providing >27 kg of the targeted triazinanone intermediate per batch in 56% overall yield with satisfactory purity.",10.1021/acs.oprd.3c00502,2024-04-03,0.7534667142137865
Tetrahedron,"First synthesis of (1R,2R,3S,9S,9aR)-1,2,3,9-tetrahydroxy-quinolizidine, a novel isosteric homologue of the glucosidase inhibitor castanospermine",,10.1016/s0040-4039(00)93488-9,1991-09-01,0.753385433413936
Tetrahedron,"Synthesis of marchantin C, a novel microtubule inhibitor from liverworts",,10.1016/j.tetlet.2010.03.125,2010-04-07,0.753385433413936
Synlett,Synthesis of the Hypoxic Signaling Inhibitor Furospongolide,The first synthesis of the marine HIF-1 inhibitor furospongolide has been achieved in eight linear steps from geranyl acetate. Key steps include Schlosser sp³-sp³ cross-coupling and Sonogashira alkynylation of β-bromobutenolide.,10.1055/s-0030-1260329,2011-09-27,0.7532853953484431
Organic Process Research & Development,Practical and Scalable Synthesis of a Glucokinase Activator via One-Pot Difluorination and Julia Olefination,"We describe the process research and development of a practical synthesis of glucokinase activator 1 as a potential drug for treating type 2 diabetes mellitus. The key structure, a 3,4- cis -difluorinated cyclopentane moiety, was constructed via diastereoselective epoxidation, followed by one-pot difluorination with Et 3 N·3HF and perfluorobutanesulfonyl fluoride (PBSF). Julia olefination of benzothiazol-2-yl sulfone with glyoxylate furnished an E / Z mixture of acrylate, followed by isomerization of the alkene to the desired E configuration during the formation of the acid chloride in the final step. This development achieved a highly practical process route to 1 (15% overall yield, 12 steps). This process route overcomes the drawbacks of the original medicinal chemistry synthetic route, which used hazardous and costly reagents (LiAlH 4, OsO 4, and Deoxo-Fluor) and had low efficiency (<4% overall yield, 20 steps).",10.1021/acs.oprd.0c00180,2020-06-16,0.7522559935496411
Organic Process Research & Development,"The Development of a Large-Scale Synthesis of Matrix Metalloproteinase Inhibitor, ABT-518",A process for the preparation of matrix metalloproteinase inhibitor ABT-518 has been developed. Significant improvements have been made to the first generation synthesis and are described here. The new process is very robust and efficient; multikilogram quantities of the title compound have been synthesized for clinical trials. ABT-518 was prepared by this six-step synthetic sequence in 51% overall yield with >99% ee.,10.1021/op025525l,2002-05-01,0.7521537782947667
Tetrahedron,"Synthesis of 2-acetamido-1,2,4-trideoxy-1,4-imino-d-galactitol, A new hexosaminidase inhibitor",,10.1016/s0040-4039(00)79188-x,1993-05-01,0.7520730449286583
Tetrahedron,A new synthesis of the glyoxalase-I inhibitor COTC,,10.1016/s0040-4039(00)00103-9,2000-03-01,0.7520730449286583
Journal of Organic Chemistry,Practical Formal Total Syntheses of the Homocamptothecin Derivative and Anticancer Agent Diflomotecan via Asymmetric Acetate Aldol Additions to Pyridine Ketone Substrates,"Two practical, efficient, and scalable asymmetric routes to DE ring fragment 7, a key building block in the synthesis of the homocamptothecin derivative diflomotecan 4, are described. The ""acetal route"" starts from 2-chloro-4-cyanopyridine 8 and represents an enantioselective and optimized modification of the original racemic discovery chemistry synthesis. The inefficient optical resolution procedure was replaced by an efficient asymmetric acetate aldol addition (dr 87:13) to a ketone substrate as the key step generating the (R)-configured quaternary stereocenter with high stereoselectivity. 7 was finally obtained in 8.9% overall yield (er 99.95:0.05) over nine steps, avoiding chromatographic purifications and comparing favorably with the initial procedure. In the related ""amide route"" starting from 2-chloroisonicotinic acid 41, a secondary amide directing group was used to facilitate the ortho lithiation of the pyridine 3-position. The key step of this protocol again consists of a practical asymmetric acetate aldol addition (dr = 87:13). The DE ring building block 7 was thus obtained in 11.1% overall yield (er > 99.95:0.05) over nine steps requiring only one chromatographic purification.",10.1021/jo060928v,2006-09-01,0.7516830255383632
Journal of Organic Chemistry,"Efficient Synthesis of a GABA<sub>A</sub> α<sub>2,3</sub>-Selective Allosteric Modulator via a Sequential Pd-Catalyzed Cross-Coupling Approach","A practical synthesis of 2-[3-(4-fluoro-3-pyridin-3-yl-phenyl)-imidazo[1,2-a]pyrimidin-7-yl]-propan-2-ol (1), an oral GABA(A) alpha(2/3)-selective agonist, is described. The five-step process, which afforded 1 in 40% overall yield, included imidazopyrimidine 2 and pyridine boronic acid 4 as key fragments. The synthesis is highlighted by consecutive Pd-catalyzed coupling steps to assemble the final free base 1 in high yield and regioselectivity. A novel method for Pd removal in the final step is also described.",10.1021/jo050741o,2005-06-29,0.7515156887422046
Organic Process Research & Development,"Process Development for a Key Synthetic Intermediate of LY2140023, a Clinical Candidate for the Treatment of Schizophrenia","To fuel clinical development of the experimental CNS medicine LY2140023, we developed a scalable route for the multistep synthesis of a pivotal synthetic intermediate. The core of the conformationally restricted glutamic acid-based amino acid analogue was built via a Rh-catalyzed cyclopropanation of thiophene. Regioselective functionalization of the remaining double bond was achieved by a hydroboration/oxidation sequence followed by a Bucherer–Bergs reaction to give a hydantoin with the targeted l -glutamic acid configuration. Subsequent resolution, oxidation state, and protecting group manipulations gave the key intermediate in an overall nine-step scalable streamlined route starting from thiophene.",10.1021/op100325h,2011-09-27,0.7513540160236104
Organic Process Research & Development,"Synthesis of Vixotrigine, a Use-Dependent Sodium Channel Blocker. Part 1: Development of Bulk Supply Routes to Enable Proof of Concept","Two syntheses of vixotrigine are reported. Route 1, adapted from the medicinal chemistry route, enabled rapid delivery of drug substance for clinical development. Route 2, which was developed to address many of the limitations of Route 1, was used to manufacture pilot quantities of API. Key features of Routes 1 and 2 are the generation of a chiral ketone intermediate from an ( S )-pyroglutamic acid derivative and catalytic reduction to introduce the second stereogenic center into the API with high stereoselectivity. Route 2 was developed to address the purification burden attributable to “benzyne-derived” impurities generated in Route 1. The improved process eliminated the possibility of the formation of these impurities, substantially improved the stereoselectivity in the reduction of the alternate cyclic imine intermediate 22, and gave a pilot plant process with significantly enhanced yield and throughput.",10.1021/acs.oprd.0c00382,2020-11-24,0.7511482968791587
Synthesis,A Practical Synthesis of a Potent and Selective Diacylglycerol Acyltransferase-1 (DGAT-1) Inhibitor,"A practical synthesis of a potent, selective, and orally efficacious diacylglycerol acyltransferase-1 (DGAT-1) inhibitor, is described. This synthesis is suitable for multi-kilogram scale with high regioselectivity and stereoselectivity. The synthesis involves a Knoevenagel condensation with Meldrum’s acid followed by the stereoselective addition of phenyl cuprate, regioselective Friedel–Crafts acylation, cyclization, and a regioselective reduction through an enol triflate with catalytic platinum oxide to provide the desired compound in 5.2% yield over 12 steps.",10.1055/s-0034-1378653,2014-08-25,0.7505311488595432
Organic Process Research & Development,Development of a Scalable Synthesis of a GPR40 Receptor Agonist,"Early process development and salt selection for AMG 837, a novel GPR40 receptor agonist, is described. The synthetic route to AMG 837 involved the convergent synthesis and coupling of two key fragments, ( S )-3-(4-hydroxyphenyl)hex-4-ynoic acid ( 1 ) and 3-(bromomethyl)-4′-(trifluoromethyl)biphenyl ( 2 ). The chiral β-alkynyl acid 1 was prepared in 35% overall yield via classical resolution of the corresponding racemic acid (±)-1 . An efficient and scalable synthesis of (±)-1 was achieved via a telescoped sequence of reactions including the conjugate alkynylation of an in situ protected Meldrum’s acid derived acceptor prepared from 3 . The biaryl bromide 2 was prepared in 86% yield via a 2-step Suzuki−Miyaura coupling−bromination sequence. Chemoselective phenol alkylation mediated by tetrabutylphosphonium hydroxide allowed direct coupling of 1 and 2 to afford AMG 837. Due to the poor physiochemical stability of the free acid form of the drug substance, a sodium salt form was selected for early development, and a more stable, crystalline hemicalcium salt dihydrate form was subsequently developed. Overall, the original 12-step synthesis of AMG 837 was replaced by a robust 9-step route affording the target in 25% yield.",10.1021/op1003055,2011-03-27,0.7505184836561032
Organic Process Research & Development,An Improved Process for the Synthesis of 5-Bromo-3-(1-methylpiperidin-4-yl)-1<i>H</i>-indole: A Key Intermediate in the Synthesis of Naratriptan Hydrochloride,"An improved process has been developed for the synthesis of 5-bromo-3-(1-methylpiperidin-4-yl)-1 H -indole, a key intermediate of naratriptan hydrochloride, which is used as a drug for migraine. A novel one-pot synthetic procedure using triethyl silane was developed for scale-up.",10.1021/op100018r,2010-05-25,0.7504734319778119
Tetrahedron,"Synthesis of aldophosphamide, a key cyclophosphamide metabolite",,10.1016/s0040-4039(01)83797-7,1977-01-01,0.7502917030097396
Tetrahedron,"Synthesis of 4,9-diethoxy-5,6,(7),8-trimethoxy-1,3-dihydronaphtho-(2,3-)-furan-1-one: A key synthon of fredericamycin A",,10.1016/s0040-4039(00)95754-x,1987-01-01,0.7502917030097396
Tetrahedron,Expeditious synthesis of a key C9–C21 subunit of the aplyslatoxine and oscillatoxins,,10.1016/s0040-4039(00)97305-2,1990-01-01,0.7502917030097396
Organic Process Research & Development,Application of an Enantiomerically Pure Bicyclic Thiolactone in the Synthesis of a Farnesyl Transferase Inhibitor,"An efficient manufacturing route to a novel farnesyl transferase inhibitor is described. The target molecule is a pro-drug, and its synthesis is complicated by the presence of labile functionality. The Medicinal Chemistry synthesis required trityl mercaptan to introduce a thiol group stereospecifically. An important objective of a new route was avoidance of such an atom-inefficient protecting group, and this was achieved by use of a bicyclic thiolactone. Reduction of the thiolactone with DIBAL afforded a masked aldehyde which participated cleanly in the key reductive amination step without loss of stereochemical integrity. The reported procedure for making the thiolactone was found to give inconsistent results. Development work resulted in a telescoped process that was operated successfully and reproducibly on the large scale. Removal of an N-Boc protecting group in the final step of the drug synthesis required careful choice of conditions to avoid cleaving other ester groups in the molecule. An impurity formed in the deprotection step was identified as the S- tert- butyl analogue arising from attack of the tert -butyl cation on the methionine residue; its identity was confirmed by independent synthesis.",10.1021/op700218j,2008-02-16,0.7500225802466457
Tetrahedron,A novel synthesis of a key intermediate for diltiazem,,10.1016/s0040-4039(01)01762-2,2001-11-01,0.7495312330728344
Organic Process Research & Development,Synthesis of the NK1 Receptor Antagonist GW597599. Part 1: Development of a Scalable Route to a Key Chirally Pure Arylpiperazine,"GW597599 1 is a novel NK-1 antagonist currently under investigation for the treatment of CNS disorders and emesis. The initial synthetic route devised from the medicinal chemistry one, used several hazardous reagents, gave low yields, and produced high levels of wastes. By targeted process of research and development, application of novel techniques, and extensive route scouting, a novel synthetic route for GW597599 has been developed. This paper reports the optimisation work of the first stage in the chemical synthesis of GW597599: the development of a pilot-plant suitable process for the synthesis of the arylpiperazine derivative 7 in an optically pure fashion. In particular, the process definition allowed eliminating the initial need for cryogenic conditions and copper catalysis in Grignard chemistry. It also allowed replacing a classical resolution step with a more efficient dynamic kinetic resolution, substantially enhancing the overall yield and throughput.",10.1021/op800146d,2008-10-16,0.7494636927611339
Organic Process Research & Development,Early Process Development of an Irreversible Epidermal Growth Factor Receptor (EGFR) T790 M Inhibitor,"The original synthesis of the irreversible epidermal growth factor receptor (EGFR) T790 M inhibitor 1 was enabled by successful application of ammonium hydroxide to cleanly cleave the N -hydroxymethyl group and by development of high yielding conditions for the subsequent amidation reaction. Furthermore, a protection-free and regioselective new synthetic route was developed that shortened the synthesis from the original 8 steps to 6 steps and improved the overall yield from 5% to 34% on scale. Crystallizations of 1 and intermediates were correspondingly developed to control the quality en route.",10.1021/acs.oprd.8b00437,2019-01-31,0.7493065632281816
Journal of Organic Chemistry,Synthesis of Cribrostatin 6,"The synthesis of cribrostatin 6 (1) is described. A regioselective bromination, a biaryl coupling, and an intramolecular cyclization are the key steps in the synthesis.",10.1021/jo801694w,2008-08-30,0.748882989183161
Organic Process Research & Development,Development of a Practical Synthesis of a TORC1/2 Inhibitor: A Scalable Application of Memory of Chirality,"Progression toward a scalable synthesis of TORC1/2 inhibitor bulk drug, culminating in the first GMP manufacturing campaign, is described. Process research and development was needed to obtain the prerequisite stereocenter in high enantiomeric excess for kilogram-scale production. Through route selection, a six-linear step synthesis was developed which afforded the API in 20% overall yield. Development included an application of memory of chirality (MOC) to install a quaternary chiral center with near complete retention, a reductive cyclization to form a piperazinone core, and a palladium-catalyzed C–C bond-forming step.",10.1021/op300330f,2013-03-31,0.7488659426470113
Synthesis,"Regioselective Synthesis ofa Potent Src Kinase Inhibitor: 4-(2,4-Dichloro-5-methoxyphenylamino)-7-methoxy-8-(2-morpholin-4-ylethoxy)benzo[<i>g</i>]quinoline-3-carbonitrile","The regioselective synthesis of compound 3, a potent Src kinase inhibitor is described. A key step in this synthesis is the regio­selective thermal rearrangement of a substituted benzocyclobutene to provide a 2,3,6,7-tetrasubstituted naphthalene. An efficient route to the uniquely substituted benzocyclobutene is reported.",10.1055/s-2003-40872,2003-08-01,0.7484841236639852
Organic Process Research & Development,"Development of a Scalable Synthesis of a Pyridinyl-3-azabicyclononene, a Novel Nicotinic Partial Agonist","The process research and development of two syntheses of a novel nicotinic partial agonist, TC-8817 ( (+)-5 ), are described. The original Medicinal Chemistry route had multiple flaws, making it unsuitable for further development. A second approach was explored which was more amenable to optimization. The key steps were an intramolecular Lewis acid-promoted cyclization, a dibromination/elimination sequence to provide a vinyl bromide, and subsequent Suzuki coupling with 3-pyridineboronic acid. The overall yield of ∼3–16% over nine steps was offset by the low cost of goods and ease of synthesis. A major drawback was the need for simulated moving bed chiral separation on the penultimate intermediate to afford the subsequently desired single enantiomer version. A third-generation, asymmetric variation afforded a key intermediate in good yield and enantiomeric purity, providing proof of concept for a more efficient production of the desired ( + )-enantiomer.",10.1021/op400002r,2013-02-09,0.7482954864166345
Organic Process Research & Development,"Improved Synthesis of RO4858542, a 5-HT<sub>6</sub> Receptor Antagonist","An improved synthesis of a 5-HT 6 antagonist is described. A problematic amide reduction step was avoided by a reductive amination. Overall, 2.9 kg was produced over 6 steps with an overall yield of 56%.",10.1021/op900319p,2010-01-29,0.7482164919234748
Organic Process Research & Development,"Development of a Practical Synthesis of Toll-like Receptor Agonist PF-4171455: 4-Amino-1-benzyl-6-trifluoromethyl-1,3-dihydroimidazo [4,5-<i>c</i>] pyridin-2-one","The development and implementation of a scalable process for the manufacture of the Toll-like receptor (TLR7) agonist PF-4171455 ( 1 ) is described. Initial routes used to synthesise 1 in milligram quantities were unsuitable for large-scale synthesis to provide bulk material. As part of the transfer between Medicinal Chemistry and Research-API, collaboration provided a fit for purpose route for the kilo-scale synthesis of 1 . Key aspects of the synthesis included (i) a safe and practical synthesis of a key nitropyridone intermediate 7 over four steps, (ii) a sequential regioselective chlorination to selectively functionalise 7 and (iii) use of a carbamate as a tethered carbonyl group, allowing an efficient regiospecific synthesis of 1 .",10.1021/op200021a,2011-05-09,0.7479675794666767
Organic Process Research & Development,Kilogram Synthesis of a Second-Generation LFA-1/ICAM Inhibitor,"The process development and the kilogram-scale synthesis of BMS-688521 ( 1 ) are described. The synthesis features a highly efficient telescoped sequence which utilizes previously described spirocyclic hydantoin ( 4b ) to produce the final intermediate via an SN AR reaction. A final deprotection step affords BMS-688521 ( 1 ) in high quality with an overall yield of 65% from the key intermediate, spirocyclic hydantoin ( 4b ).",10.1021/op100225g,2010-11-29,0.7477349883669364
Synlett,Evolution of the Process for the Preparation of a Selective ErbB VEGF Receptor Inhibitor,"An efficient synthetic route to the potent and selective ErbB VEGF receptor inhibitor, BMS-690514 ( 1 ) is described. Strategic modifications in both approach and procedure addressed several issues, which led to a safe, efficient, and economical process for the preparation of multi-kilogram quantities of 1 . The convergent route involves alkylation of a suitably protected (3 R ,4 R )-4-aminopiperidin-3-ol with the triethyl(alkyl)ammonium salt of a functionalized pyrrolotriazine 3a followed by deprotection to provide 1 as the crystalline free base.",10.1055/s-0032-1317540,2012-11-23,0.7476498944920118
Organic Letters,Asymmetric Synthesis of Akt Kinase Inhibitor Ipatasertib,"A highly efficient asymmetric synthesis of the Akt kinase inhibitor ipatasertib (1) is reported. The bicyclic pyrimidine 2 starting material was prepared via a nitrilase biocatalytic resolution, halogen-metal exchange/anionic cyclization, and a highly diastereoselective biocatalytic ketone reduction as key steps. The route also features a halide activated, Ru-catalyzed asymmetric hydrogenation of a vinylogous carbamic acid to produce α-aryl-β-amino acid 3 in high yield and enantioselectivity. The API was assembled in a convergent manner through a late-stage amidation/deprotection/monohydrochloride salt formation sequence.",10.1021/acs.orglett.7b02228,2017-08-31,0.7475677070545341
Organic Process Research & Development,Development of a Concise Process for the Synthesis of the Azaindazole Core of the CD73 Inhibitor AB680,"AB680 is a highly potent small-molecule CD73 inhibitor discovered and developed by Arcus Biosciences, currently in clinical trials for the treatment of pancreatic cancer. Herein, we report a concise synthesis of 4,6-dichloro-1H-pyrazolo[3,4- b ]pyridine 3, which is the central azaindazole core of AB680. The process consists of four synthetic operations and three isolations, including a PMB-protected pyrazole formation, a telescoped two-step cyclization and aromatization sequence, and finally a one-pot PMB deprotection and chlorination to furnish 3 . This chemistry was successfully scaled up to provide >200 g of 3 in 44% overall yield and 97.6% HPLC purity. Overall, the route developed toward 3 represents an efficient construction of an azaindazole core, which is a synthetically challenging yet prevalent structural motif.",10.1021/acs.oprd.3c00056,2023-04-19,0.7473951313582087
Synthesis,Convergent Synthesis of Immune Inhibitor IMMH002,"Abstract A convergent synthesis of IMMH002 in 36% overall yield starting from bromobenzene is described with a key Suzuki–Miyaura cross-coupling reaction used to provide a crucial intermediate. The route does not require column chromatography and solves the most intractable quality problem caused by a homologue by-product in the original linear synthesis. Furthermore, reducing the use of Lewis acid mediated reactions improves the environmental impact of the synthesis and reduces overall waste. The new route described herein is more efficient, convenient, reliable, and economically more viable when compared to the previously reported linear route.",10.1055/s-0040-1706299,2020-10-14,0.7473409078484723
Organic Process Research & Development,Development of a Scalable Synthesis of Dipeptidyl Peptidase-4 Inhibitor ABT-279,"A convergent, scalable synthesis of dipeptidyl peptidase-4 inhibitor, ABT-279, has been developed and demonstrated on multikilogram scale. The cis -2,5-disubstituted pyrrolidine is generated by cyclization of a Boc-amine onto an alkynyl ketone followed by stereospecific reduction of the resulting acyliminium intermediate. The amine coupling partner was prepared by a novel Hofmann rearrangement promoted by 1,3-dibromo-5,5-dimethylhydantoin. The final product was isolated as the l -malic acid salt. The scale-up campaign consisted of 15 steps and delivered 42 kg of ABT-279 in 14% overall yield. A second-generation synthesis that addresses some of the issues encountered during scale-up was developed and demonstrated on kilogram scale.",10.1021/op900197r,2009-10-15,0.7472666747295742
Organic Letters,Practical and Cost-Effective Manufacturing Route for the Synthesis of a β-Lactamase Inhibitor,"Compound 1, a potent and irreversible inhibitor of β-lactamases, is in clinical trials with β-lactam antibiotics for the treatment of serious and antibiotic-resistant bacterial infections. A short, scalable, and cost-effective route for the production of this densely functionalized polycyclic molecule is described.",10.1021/ol4031606,2013-12-13,0.7472266777344571
Tetrahedron,A stereocontrolled synthetic route to the C1C18 subunit of pamamycin-607,,10.1016/s0040-4039(02)00655-x,2002-05-01,0.747205268691538
Tetrahedron,A synthetic route to pyoluteorin,,10.1016/s0040-4039(01)98051-7,1970-01-01,0.747205268691538
Tetrahedron,A synthetic route to carbocyclic aminonucleosides,,10.1016/0040-4039(76)80055-x,1976-08-01,0.747205268691538
Tetrahedron,A synthetic route to thionolactones,,10.1016/0040-4039(81)80113-x,1981-01-01,0.747205268691538
Tetrahedron,A synthetic route to aspidospermine and quebrachamine,,10.1016/s0040-4039(01)99714-x,1966-01-01,0.747205268691538
Tetrahedron,The first synthetic route to furostan saponins,,10.1016/s0040-4039(00)01889-x,2001-01-01,0.747205268691538
Organic Process Research & Development,"Development of an Efficient and Practical Route for the Multikilogram Manufacture of Ethyl 5-Cyano-2-methyl-6-oxo-1,6-dihydropyridine-3-carboxylate and Ethyl 6-Chloro-5-cyano-2-methylnicotinate, Key Intermediates in the Preparation of P2Y12 Antagonists","Elucidation of the mechanism of formation of two major impurities in the synthetic route towards key intermediate ethyl 5-cyano-2-methyl-6-oxo-1,6-dihydropyridine-3-carboxylate 1, led directly to the development of a route with significant process improvements in terms of yield, purity, and operability. The overall process yield increased from 15% to 73% without the need for extra purification steps, giving the key intermediate ethyl 6-chloro-5-cyano-2-methylnicotinate, 2, in excess of 80 kg to support clinical development.",10.1021/op200368m,2012-04-20,0.7471518646369658
Organic Process Research & Development,Manufacture of the PI3K β-Sparing Inhibitor Taselisib. Part 1: Early-Stage Development Routes to the Bromobenzoxazepine Core,"Two convergent regioselective routes for the synthesis of the tetracyclic imidazobenzoxazepine triazole 1, a key intermediate toward the synthesis of taselisib, are described. In the first-generation route, a chemoselective Negishi cross-coupling reaction was developed between iodoimidazole 3 and triazole 7, which enabled the delivery of initial kilogram quantities of 1 . Because of the inefficiencies in the preparation of the imidazole 3, a second-generation route via a highly regioselective imidazole ring formation between α-chloroketone 11 and aryl amidine 12 was developed. The resulting imidazole 14 provided the handle to efficiently install the seven-membered benzoxazepine ring system in one pot with two-step N -alkylation and S N Ar tandem reactions.",10.1021/acs.oprd.9b00049,2019-03-06,0.746829888852917
Journal of Organic Chemistry,Studies on the Total Synthesis of Lactonamycin:  Synthesis of the CDEF Ring System,"A concise and efficient synthesis of the tetracyclic CDEF ring system of lactonamycin (1) is described. The key step involved the Lewis acid mediated, intramolecular Friedel-Crafts acylation of carboxylic acid 6 to produce the tetracyclic CDEF core structure of target 1. The synthesis of 6 was carried out using a high-yielding Negishi coupling of benzyl bromide 7 with triflate 8, which was accessible in 11 steps and 31% overall yield on a multigram scale starting from trihydroxy acid 9.",10.1021/jo0613378,2006-09-19,0.7468234814669157
Organic Process Research & Development,Process Development and Multikilogram-Scale Synthesis of a TRPV1 Antagonist,"The process development and multikilogram preparation of a TRPV1 antagonist, 1, is described. Pyrido[2,3- b ]pyrazine 1 was prepared in a convergent manner by the coupling of two key fragments, glyoxal 2 and diamine 3 . Glyoxal 2 was synthesized in six chemical steps in 20% overall yield, the key step being a challenging Grignard reaction to install the glyoxalate moiety. Diamine 3 was also prepared in six chemical steps in 46% overall yield, exploiting a regioselective nucleophilic aromatic substitution to obtain the key nitrodiamine intermediate 19 .",10.1021/op400304h,2013-11-21,0.7466360972440721
Synthesis,"First Total Synthesis of (-)-Circumdatin H, a Novel Mitochondrial NADH Oxidase Inhibitor","An efficient and highly convergent synthesis of the mitochondrial NADH oxidase inhibitor (-)-circumdatin H is described. The strategy employs the intramolecular Eguchi aza-Wittig protocol as a key step to install the crucial central core BC ring system, leading to the first total synthesis of the target molecule.",10.1055/s-0029-1218606,2009-12-16,0.7465936745927262
Journal of the American Chemical Society,Twelve-Step Asymmetric Synthesis of (−)-Nodulisporic Acid C,"A short, enantioselective synthesis of (-)-nodulisporic acid C is described. The route features two highly diastereoselective polycyclizations en route to the terpenoid core and the indenopyran fragment and a highly convergent assembly of a challenging indole moiety. Application of this chemistry allows for a 12-step synthesis of the target indoloterpenoid from commercially available material.",10.1021/jacs.8b09965,2018-09-28,0.7454762947833602
Organic Process Research & Development,"Fit-for-Purpose Synthesis of a KRAS<sup>G12C</sup> Covalent Inhibitor, via a Diastereoselective Hayashi Arylation","An enabling, fit-for-purpose synthesis of stereochemically pure KRAS G12C covalent inhibitor 1, a potential new treatment for cancer, is described. The synthetic route provided 1 in 13 steps from commercially available 2-fluoro-5-methylaniline ( 2 ), tert -butyl ( S )-3-methylpiperazine-1-carboxylate ( 8 ) and ( S )-(1-methylpyrrolidin-2-yl)methanol ( 10 ). A key transformation in this sequence was the diastereoselective 1,4-addition of an aryl boronate derived from 2 with rac- 4-methylcyclohex-2-en-1-one ( rac- 4 ) in a Hayashi arylation that sets two relative stereocenters of the target molecule. This in turn inspired the development of an improved synthesis of ( R ) - 4-methylcyclohex-2-en-1-one (( R ) - 4 ) via optimized methodology for the asymmetric monohydrogenation of 1,4-dienes, thus setting the stage for a fully asymmetric synthesis of inhibitor 1 .",10.1021/acs.oprd.4c00211,2024-07-22,0.7453496788558976
Journal of Organic Chemistry,Synthesis of novel 6-deoxyanthracyclines,"An extremely direct route to the 6-deoxyanthracycline skeleton is described. The initial route to quinone 10 failed due to an unexpected complication in the Ago demethylation step. However, starting from 2-bromo- 1,4-dimethoxynaphthalene, furan 17 could be prepared in two steps. Furan 17 was then converted into anthraquinone 19 in five steps. The eight-step route proceeds in 9% overall yield.",10.1021/jo00218a002,1985-09-01,0.7452643033086417
Journal of Organic Chemistry,"A Short, Stereocontrolled, and Practical Synthesis of α-Methylomuralide, a Potent Inhibitor of Proteasome Function","An efficient and practical synthesis of alpha-methylomuralide (3), a selective inhibitor of proteasomes, has been developed as outlined in Scheme 1. Among the advantages of this route of synthesis over previously described approaches are (1) ease of scale-up and (2) high yields (28% overall yield of alpha-methylomuralide from 6) and stereocontrol (including high enantiocontrol). The synthesis is well suited to the production of 3 in the quantities needed for material-intensive in vivo investigations.",10.1021/jo0268916,2003-02-20,0.7451959351469418
Organic Process Research & Development,Process Development toward a Pro-Drug of <i>R</i>-Baclofen,"This paper describes the process development conducted toward the multi-kilogram synthesis of a novel transported pro-drug of R -baclofen. The key steps in the synthesis were the enzyme-catalyzed kinetic resolution of isopropyl(methylthiocarbonyloxy)methyl-2-methylpropionate using Candida antarctica lipase A to provide the desired ( S )-enantiomer. This was followed by the reaction with sulfuryl chloride and N -hydroxysuccinimide to produce ( S ) 1-(2,5-dioxoazolidinyloxycarbonyloxy)-2-methylpropyl 2-methylpropanate. The synthesis of ( S ) 1-(2,5-dioxoazolidinyloxycarbonyloxy)-2-methylpropyl 2-methylpropanate enabled the efficient use of R -baclofen in the final coupling stage of the synthesis. The new route reported here is more efficient and sustainable than those reported previously and had the potential to become the commercial route of manufacture.",10.1021/acs.oprd.0c00491,2020-12-15,0.7449788806405165
Organic Process Research & Development,"Discovery and Development of an Efficient, Scalable, and Robust Route to the Novel CENP-E Inhibitor GSK923295A","The discovery and development of an efficient manufacturing route to the CENP-E inhibitor 3-chloro- N -{(1 S )-2-[( N, N -dimethylglycyl)amino]-1-[(4-{8-[(1 S )-1-hydroxyethyl]imidazo[1,2- a ]pyridin-2-yl}phenyl)methyl]ethyl}−4-[(1-methylethyl)oxy]benzamide (GSK923295A) is described. The existing route to GSK923295A was expensive, nonrobust, used nonideal reagents, and consistently struggled to deliver the API needed for clinical studies. The new synthesis commences from the readily available l -phenylalaninol, which is smoothly converted through to GSK923295A using key Friedel−Crafts acylation as well as selective acylation chemistries. Downstream chemistry to GSK923295A is both high yielding and robust, and the resulting process has been demonstrated first on the kilo scale and subsequently in the pilot plant where 55 kg was successfully prepared. The resulting process is simple, uses cheaper raw materials, is greener in that it avoids using aluminum, tin, and bromination chemistries, and obviates the need for chromatographic purification. Also discussed are the route derived impurities, how they were unambiguously prepared to confirm structure and processing amendments to control their formation, and enhancements to the new process to facilitate future processing.",10.1021/op100186c,2010-08-10,0.7449764522387577
Tetrahedron,The naphthalene route to anthracyclinones,,10.1016/s0040-4039(01)94520-4,1979-01-01,0.7449396351308324
Tetrahedron,E. Dane's route to estrone revisited,,10.1016/s0040-4039(00)92705-9,1991-07-01,0.7449396351308324
Tetrahedron,A Flexible Route to [4.1.1]Propellanes,,10.1016/s0040-4039(97)01545-1,1997-09-01,0.7449396351308324
Tetrahedron,A Garratt-Braverman route to isoindolines and phthalans,,10.1016/j.tetlet.2019.02.029,2019-02-19,0.7449396351308324
Tetrahedron,Photodecarbonylation - a gentle route to annelated cyclohexadienes,,10.1016/s0040-4039(00)99973-8,1970-01-01,0.7449396351308324
Tetrahedron,"A holegenocyclisation route to 1,2,4-trioxanes",,10.1016/0040-4039(93)88126-4,1993-10-01,0.7449396351308324
Tetrahedron,The naphthalene route to anthracyclinones,,10.1016/s0040-4039(01)86126-8,1979-01-01,0.7449396351308324
Tetrahedron,"Versatility of the cyclo-oxymercuriation route to 1,2,4-trioxanes",,10.1016/s0040-4039(96)02359-3,1997-01-01,0.7449396351308324
Tetrahedron,The isoxazoline-5-spirocyclopropane route to (±)-Pumiliotoxin C,,10.1016/s0040-4039(00)61023-7,1992-10-01,0.7449396351308324
Tetrahedron,Trifluoroacetoxysulphenylation of unsaturated nitriles as a route to lactones,,10.1016/s0040-4039(00)85194-1,1986-01-01,0.7449396351308324
Tetrahedron,"A tethered aminohydroxylation route to l-arabino-[2R,3S,4R] and l-xylo-[2R,3S,4S]-C18-phytosphingosines",,10.1016/j.tetlet.2009.02.173,2009-02-27,0.7449396351308324
Tetrahedron,A carbene route to dehydro[m.n.]paracyclophanes,,10.1016/s0040-4039(00)78740-5,1980-01-01,0.7449396351308324
Tetrahedron,"A flexible, modular route to cyclopentanols",,10.1016/j.tetlet.2009.09.157,2009-10-02,0.7449396351308324
Synthesis,A [4+2] Heterocycloaddition Route to (±)-9-Decanolides,International audience,10.1055/s-2003-37657,2003-01-01,0.7449396351308324
Tetrahedron,A route to 8-azaestrone,,10.1016/s0040-4039(01)90875-5,1963-01-01,0.7449396351308324
Tetrahedron,Concerning the cycloelimination route to oxirenes,,10.1016/0040-4039(75)80012-8,1975-01-01,0.7449396351308324
Tetrahedron,An annelation route to quionones,,10.1016/s0040-4039(01)91508-4,1978-01-01,0.7449396351308324
Tetrahedron,A nitrosamine route to (±)-macrostomine,,10.1016/s0040-4039(00)93647-5,1980-01-01,0.7449396351308324
Tetrahedron,The Isoxazoline Route to α-Methylen Lactones.,,10.1016/s0040-4039(00)87961-7,1983-01-01,0.7449396351308324
Tetrahedron,The isobenzofuran route to anthracyclinones,,10.1016/s0040-4039(01)83286-x,1977-01-01,0.7449396351308324
Tetrahedron,5-Phenylpyridazinones-A serendipitous route from coumarins,,10.1016/j.tetlet.2008.05.015,2008-05-10,0.7449396351308324
Tetrahedron,Beckmann fragmentation of α-difluoramino fluorimines; a route to α-difluoramino fluorides,,10.1016/s0040-4039(00)90906-7,1967-01-01,0.7449396351308324
Tetrahedron,The anionic route to tricyclanes,,10.1016/s0040-4039(99)02270-4,2000-02-01,0.7449396351308324
Tetrahedron,The phosphaalkene-phosphenium cations (R2N)2C=P-P+-NR′2 a route towards diphosphenes and phosphaallylic cations,,10.1016/0040-4039(91)85083-h,1991-06-01,0.7449396351308324
Tetrahedron,A -glycoside route to leukotrienes,,10.1016/s0040-4039(01)90546-5,1981-01-01,0.7449396351308324
Tetrahedron,Indoloquinones from azomethine ylides via the 4-oxazoline route,,10.1016/s0040-4039(00)99082-8,1989-01-01,0.7449396351308324
Tetrahedron,Photocyclization of benzalcycloalkanone oximes. A photoannulation route to quinolines.,,10.1016/s0040-4039(00)92352-9,1991-09-01,0.7449396351308324
Tetrahedron,C-nitrosation of unsaturated amides. A route to 2-pyrone imines,,10.1016/s0040-4039(00)75093-3,1975-01-01,0.7449396351308324
Synthesis,"A Two-step Synthesis of the Anti-cancer Drug (R,S)-Bicalutamide","A short, efficient synthesis of the non-steroidal antiandrogen (R,S)-bicalutamide is presented. This new route generates bicalutamide in only two steps with an overall yield of 73%. The key step is a 1,2 addition of a methyl sulfone to a keto-amide.",10.1055/s-2002-28508,2002-01-01,0.7446232684788161
Journal of Organic Chemistry,Practical Asymmetric Synthesis of a Non-Peptidic α<sub>v</sub>β<sub>3</sub> Antagonist,"The development of a practical and highly convergent synthesis of an alpha(v)beta3 antagonist is described. The two key fragments present in this compound, a tetrahydropyrido[2,3-b]azepine ring system and a chiral 3-aryl-5-oxopentanoic acid, were constructed independently and then coupled at a late stage using a Wittig reaction. The pyridoazepine moiety was prepared from N-Boc 6-chloro-2-aminopyridine via directed ortho-metalation/alkylation followed by in situ cyclization. A Suzuki reaction was then used to attach the propionaldehyde side-chain required for Wittig coupling. The coupling partner was prepared from asymmetric methanolysis of a 3-substituted glutaric anhydride followed by elaboration of the acid moiety to the requisite beta-keto phosphorane. Using this route, kilogram quantities of the desired drug candidate were prepared.",10.1021/jo048082n,2005-02-05,0.7444664783526961
Tetrahedron,A novel synthetic route to the hexahydrobenzofuran subunit of the avermectins and milbemycins,,10.1016/s0040-4039(00)85135-7,1986-01-01,0.7443858470490214
Tetrahedron,"A novel synthetic route to morpholin-2,3-diones from 2-aminoalcohols",,10.1016/0040-4039(96)00800-3,1996-06-01,0.7443858470490214
Organic Process Research & Development,A Convergent Process for the Preparation of Adamantane 11-β-HSD-1 Inhibitors,"A convergent, scalable process was developed for the synthesis of adamantane 11-β-hydroxysteroid dehydrogenase-1 inhibitors E -4-(2-methyl-2-(4-(5-(trifluoromethyl)pyridin-2-yl)piperazin-1-yl)propionylamino)adamantane-1-carboxylic acid ( 1 ) and E -4-(2-methyl-2-(4-(5-(trifluoromethyl)pyridin-2-yl)piperazin-1-yl)propionylamino)adamantane-1-carboxamide ( 2 ) to rapidly deliver material for development. The process was high yielding and provided 1 in 52% overall yield over six total steps with a five-step longest linear sequence and 2 in 45% overall yield over seven total steps with a six-step longest linear sequence. A process to prepare active pharmaceutical ingredient (API) of >99% purity at the kilogram scale has been developed under tight delivery timelines.",10.1021/op800065q,2008-09-12,0.7443585367152041
Synthesis,New Synthetic Process for Bosutinib,"A new and improved synthetic route to bosutinib is described on a hectogram scale. The key step is the intramolecular cyclization of a 3-(2-aminophenyl)-3-oxopropanenitrile with N , N -dimethylformamide dimethyl acetal to form the 3-cyano-4-hydroxyquinoline ring of 7-(3-chloropropoxy)-6-methoxy-4-oxo-1,4-dihydroquinoline-3-carbonitrile. A practical synthetic method to 2,4-dichloro-5-methoxyaniline is also established. Bosutinib is obtained in 18.0% yield over nine steps from acetovanillone with 98.9% purity (HPLC).",10.1055/s-0035-1560471,2015-09-09,0.744288341676631
Synthesis,A Convenient Route to Alkaloid Lipids: Application for the Synthesis of a <b><i>Leptophylline A</i></b> Analogue,"A synthetic route for efficient access to alkaloid lipids, using the chiral 2,3,6-trisubstituted piperidine acetaldehyde 9 as an intermediate, is reported. The utility of the synthetic route was demonstrated in the asymmetric synthesis of an unnatural analogue of Cassia leptophylla alkaloid lipid, leptophyllin A, in 16 steps and 15% overall yield starting from d-glucal.",10.1055/s-2002-19302,2002-07-26,0.7442062151490053
Synthesis,Asymmetric Synthesis of a Protected Dihydroxypiperazic Acid Derivative,"A short and flexible route for the synthesis of 1,2-diisopropyl-3-methyl-(3S,4R,5R)-4,5-dihydroxyhexahydro-1,2,3-pyrid­azinetricarboxylate, from readily available acrolein, is described. This approach involves an asymmetric α-hydrazination, dihydroxylation and intramolecular cyclisation as key steps.",10.1055/s-2007-966062,2007-05-24,0.7441476780427831
Organic Process Research & Development,"Improved Synthesis of the Selective Rho-Kinase Inhibitor 6-Chloro-<i>N</i>4-{3,5-difluoro-4-[(3-methyl-1<i>H</i>-pyrrolo[2,3-<i>b</i>]pyridin-4-yl)oxy]phenyl}pyrimidin-2,4-diamine",A highly potent and selective Rho-kinase inhibitor containing a 7-azaindole moiety has been developed at Bayer Schering Pharma. Herein we disclose details of a significantly improved synthesis of the compound in 8.2% overall yield. Key aspects include cost and safety considerations and the uncommon use of a trifluoromethyl group with controllable reactivity as a masked methyl group.,10.1021/op900260k,2009-12-11,0.7441405828354266
Tetrahedron,A stereo controlled route to a key intermediate fro the synthesis of maytansine,,10.1016/s0040-4039(01)83195-6,1977-01-01,0.7440871695517373
Journal of Organic Chemistry,Practical Synthesis of a p38 MAP Kinase Inhibitor,"p38 MAP kinase inhibitors have attracted considerable interest as potential agents for the treatment of inflammatory diseases. Herein, we describe a concise and efficient synthesis of inhibitor 1 that is based on a phthalazine scaffold. Highlights of our approach include a practical synthesis of a 1,6-disubstituted phthalazine building block 24 as well as the one-pot formation of boronic acid 27. Significant synthetic work to understand the reactivity principles of the intermediates helped in selection of the final synthetic route. Subsequent optimization of the individual steps of the final sequence led to a practical synthesis of 1.",10.1021/jo802186m,2008-12-16,0.7437714143178947
Organic Process Research & Development,"Manufacturing Process for 6-Bromo-<i>N</i>,<i>N</i>-bis(4-methoxybenzyl)-4-methyl-5-(trifluoromethyl)pyridin-2-amine, a Key Intermediate in the Synthesis of KRAS G12C Inhibitor Divarasib","The densely functionalized heterocycle 6-bromo- N, N -bis(4-methoxybenzyl)-4-methyl-5-(trifluoromethyl)pyridin-2-amine ( 1 ) represents a key intermediate in the atroposelective synthesis of the potent KRAS G12C covalent inhibitor divarasib (GDC-6036). The first-generation manufacturing process of 1 comprised 9 steps, including tedious protecting group manipulations and a superstoichiometric copper-mediated trifluoromethylation of the corresponding iodopyridine using Chen’s reagent. Additional process research and development enabled an improved, scalable second-generation route furnishing 1 in only 3 steps from the readily available and inexpensive starting material 2,6-dichloro-4-methylnicotinic acid ( 13 ) via a deoxofluorination, a chlorine-to-bromine halogen exchange, and a regioselective S N Ar amination.",10.1021/acs.oprd.3c00366,2023-12-29,0.7436374727312067
Tetrahedron,An efficient route to homologated pyranosidic conjugated enals,,10.1016/s0040-4039(00)80805-9,1988-01-01,0.7435715152395803
Tetrahedron,An efficient route to 3-chlorojuglones,,10.1016/s0040-4039(00)72715-8,1989-01-01,0.7435715152395803
Tetrahedron,"An efficient route toD-myo-inositol 1,3,4-triphosphate andD-myo-inositol 1,3,4,5-tetrakisphosphate",,10.1016/s0040-4039(00)77699-4,1992-02-01,0.7435715152395803
Tetrahedron,"An efficient route to skipped diynes and triynes, (Z,Z) dienes and (Z,Z,Z) trienes.",,10.1016/0040-4039(92)89024-7,1992-09-01,0.7435715152395803
Tetrahedron,An efficient and expeditious route to stannylallenes,,10.1016/s0040-4039(01)81353-8,1984-01-01,0.7435715152395803
Tetrahedron,A short and efficient enantioselective route to a key intermediate for the total synthesis of forskolin,,10.1016/s0040-4039(00)70681-2,1989-01-01,0.7434321625431958
Organic Process Research & Development,Stereoselective and Scalable Synthesis of Potent Antibiotic RSC-435830 Through a Key Intermediate C2 (<i>S</i>)-Methylcephalosporin,"Cephalosporins are valuable antibiotics for clinical treatment of infectious diseases. RSC-435830 is a cephalosporin-containing antibiotic with a unique C2 ( S )-methylcephalosporin structure. It was a synthetic challenge to construct a chiral methyl group at the C-2 position on the cephalosporin scaffold. We report herein two routes for the stereoselective and scalable synthesis of C2 ( S )-methylcephalosporin 4, a key intermediate of RSC-435830, that has advanced to phase I clinical trials. The first route focused on stereoselective isomerization of the double bond on the cephalosporin structure without significant changes from the initial synthetic route. For the second route, we set an alternative starting material and then optimized a Mannich-type reaction followed by stereoselective reduction, to enable shortening of the reaction steps from the first route. This culminated in the synthesis of several hundred grams of the key intermediate 4 leading to RSC-435830.",10.1021/acs.oprd.5c00111,2025-05-30,0.7433666099007994
Journal of the American Chemical Society,Total Synthesis of the Sphingolipid Biosynthesis Inhibitor Fumonisin B<sub>1</sub>,"The first total synthesis of the sphingolipid biosynthesis inhibitor fumonisin B(1) has been achieved. This convergent synthesis utilizes oxonia Cope rearrangements to prepare two key homoallylic alcohols, which are then functionalized to the primary components A and B for cross-coupling. Other highlights of our approach include a new and efficient synthesis of the diprotected tricarballylic acid C and a global deprotection strategy as the final step.",10.1021/ja9009265,2009-04-08,0.7428592079236116
Organic Process Research & Development,Process Development and Pilot-Plant Synthesis of (<i>S</i>)-<i>tert</i>-Butyl 1-Oxo-1-(1-(pyridin-2-yl)cyclopropylamino)propan-2-ylcarbamate: Studies on the Scale-Up of Kulinkovich–Szymoniak Cyclopropanation,"A practical and scalable synthesis of ( S )- tert -butyl 1-oxo-1-(1-(pyridin-2-yl)cyclopropylamino)propan-2-ylcarbamate, an intermediate in the manufacture of a lymphocyte function-associated antigen 1 inhibitor, is described. The titled compound is prepared via an efficient one-pot, two-step telescoped sequence starting from readily available materials. A modified Kulinkovich–Szymoniak cyclopropanation of a nitrile followed by in situ amide formation with an activated carboxylic acid derivative afforded the target product in about 50% overall isolated yield and >97% purity.",10.1021/op300059b,2012-04-18,0.7428434655529504
Organic Process Research & Development,"The First Kilogram Synthesis of Beclabuvir, an HCV NS5B Polymerase Inhibitor","The process development and kilogram-scale synthesis of beclabuvir (BMS-791325, 1 ) is described. The convergent synthesis features the use of asymmetric catalysis to generate a chiral cyclopropane fragment and coupling with an indole fragment via an alkylation. Subsequent palladium-catalyzed intramolecular direct arylation efficiently builds the central seven-membered ring. The target was prepared in 12 linear steps with five isolations in an overall yield of 8%.",10.1021/acs.oprd.8b00214,2018-08-16,0.7427160745024444
Journal of the American Chemical Society,Alkene−Alkyne Coupling as a Linchpin:  An Efficient and Convergent Synthesis of Amphidinolide P,"A short and efficient synthesis of the cytotoxic macrolide amphidinolide P is described. A remarkably chemo- and regioselective ruthenium-catalyzed alkene-alkyne coupling allows for a convergent synthesis and demonstrates that both enynes and beta-lactones are suitable coupling partners. This work also features a novel strategy for the preparation of macrolactones via intramolecular transesterification of beta-lactones. The target structure was prepared in 15 steps for the longest linear sequence and 10% overall yield, 24 steps total.",10.1021/ja045449x,2004-09-30,0.7424000282175827
Tetrahedron,"New synthetic route to pyrimido[4,5-g]quinazoline-4,9-diones",,10.1016/j.tetlet.2015.03.085,2015-04-01,0.742308139354174
Tetrahedron,A new synthetic route to (±)-perhydrohistrionicotoxin,,10.1016/s0040-4039(00)91119-5,1975-01-01,0.742308139354174
Synthesis,"A New Synthetic Route to 2,2′-Biimidazole",,10.1055/s-1974-23443,1974-01-01,0.742308139354174
Tetrahedron,A new synthetic route to 7 α-methoxycephalosporins,,10.1016/s0040-4039(00)87510-3,1982-01-01,0.742308139354174
Tetrahedron,"A new synthetic route to perfluoroalkylidene-α,ω-bisphosphonates",,10.1016/0040-4039(94)02266-e,1995-01-01,0.742308139354174
Tetrahedron,A new synthetic route to prostaglandins,,10.1016/s0040-4039(01)96327-0,1973-01-01,0.742308139354174
Tetrahedron,A new synthetic route to benzodiazepines,,10.1016/s0040-4039(01)87352-4,1973-01-01,0.742308139354174
Tetrahedron,A new synthetic route to functionalised tricyclo [5.3.2.2.6] dodecadienes,,10.1016/s0040-4039(01)92591-2,1977-01-01,0.742308139354174
Tetrahedron,A new synthetic route to tropane alkaloids. Pseudotropine and tropacocaine,,10.1016/s0040-4039(01)91127-x,1984-01-01,0.742308139354174
Tetrahedron,A new synthetic route to symmetrical photochromic diarylperfluorocyclopentenes,,10.1016/s0040-4039(98)02688-4,1999-02-01,0.742308139354174
Tetrahedron,A new synthetic route to prostaglandins,,10.1016/s0040-4039(00)84486-x,1986-01-01,0.742308139354174
Tetrahedron,A new synthetic route to 10β-alkyldeoxoartemisinins,,10.1016/s0040-4039(99)01824-9,1999-12-01,0.742308139354174
Tetrahedron,A new synthetic route to 4-demethoxydaunomycinone,,10.1016/s0040-4039(01)95025-7,1978-01-01,0.742308139354174
Organic Process Research & Development,Process Development of the Novel LpxC Inhibitor T-1228. Part 2: Synthesis of the Malonamide Core and the Final Intermediate,"The novel LpxC inhibitor T -1228 is a candidate drug molecule for multidrug-resistant Gram-negative bacterial infection. This report describes the synthesis of the malonamide derivative,(2 S )-2-(4-iodo- N -methylbenzamido)- N 1,2-dimethyl- N 3 -((tetrahydro-2 H -pyran-2-yl)oxy)malonamide, containing the quaternary stereogenic core of the novel LpxC inhibitor T -1228 from commercially available diethyl 2-bromo-2-methylmalonate in 8 steps and 2 isolation. The quaternary stereogenic center of the malonamide core was created via enzymatic desymmetrization, by treating the malonic ester derivative, diethyl 2-(((benzyloxy)carbonyl)(methyl)amino)-2-methylmalonate, with porcine liver esterase. To control impurities that could negatively affect the quality of the drug substance, a novel approach for producing the final intermediate, ( S )-2-(4-((4-(( S )-2,2-dimethyl-1,3-dioxolan-4-yl)phenyl)ethynyl)- N -methylbenzamido)- N 1 -hydroxy- N 3,2-dimethylmalonamide, was also developed, in which a selective deprotection reaction was incorporated. Using this newly developed process chemistry route, we have successfully synthesized 38.8 kg of the malonamide derivative and 13.5 kg of the final intermediate.",10.1021/acs.oprd.5c00166,2025-10-23,0.7422141776566479
Journal of Organic Chemistry,Scalable Synthesis of a Prostaglandin EP4 Receptor Antagonist,"The evolution of scalable, economically viable synthetic approaches to the potent and selective prostaglandin EP4 antagonist 1 is presented. The chromatography-free synthesis of multikilogram quantities of 1 using a seven-step sequence (six in the longest linear sequence) is described. This approach has been further modified in an effort to identify a long-term manufacturing route. Our final synthesis involves no step requiring cryogenic (< -25 degrees C) conditions; comprises a total of four steps, only three of which are in the longest linear synthesis; and features the use of two consecutive iron-catalyzed Friedel-Crafts substitutions.",10.1021/jo1004197,2010-05-14,0.7420920399795905
Journal of Organic Chemistry,An Efficient Synthesis of a Potent PPARpan Agonist,"An efficient synthesis of 2-{4-[({4-{[4-(4-methoxyphenyl)piperazin-1-yl]methyl}-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl}methyl)thio]phenoxy}-2-methylpropanoic acid (1), a potent PPARpan agonist, is described. The seven-step synthesis, which afforded 1 in 30% overall yield, includes a highly regioselective carbon-sulfur bond formation via coupling of a bishydroxymethylthiazole (3) with 4-hydroxythiophenol, displacement of the remaining alcohol through a three-step telescoped sequence involving an efficient cleavage of an aryl mesylate, and an efficient and practical method of introducing an isobutyric acid fragment.",10.1021/jo061295n,2006-09-12,0.7420666354397624
Organic Process Research & Development,Efficient Enantioselective Synthesis of the NMDA 2B Receptor Antagonist Ro 67-8867,"An efficient, enantioselective, and scalable eight-step synthesis for the NMDA 2B receptor antagonist Ro 67-8867 ( S, S )- 1 selected for the treatment of acute ischemic stroke is described based on the coupling reaction of the amino alcohol ( S, S )- 6 with the sulfone building block 7. The synthesis of the amino alcohol ( S, S )- 6 was achieved by the highly selective asymmetric hydrogenation of the piperidinone 4*HCl proceeding with concomitant dynamic kinetic resolution to ( S, S )- 5 . Subsequent debenzylation afforded the enantiomerically pure amino alcohol ( S, S )- 6 after ee-enhancement by simple crystallization in good yield. The hydrogenation substrate 4*HCl was prepared as a stable hydrochloride in two steps from ethyl N -benzyl-3-oxo-4-piperidinecarboxylate hydrochloride ( 2 ) for which a new, short, efficient, and cheap synthesis was developed. To bypass a mutagenic intermediate, a revised safe protocol for the sulfone building block 7 was established. The new synthesis allows the access to Ro 67-8867 ( S, S )- 1 in an overall yield of 53% compared to 3.5% of the Discovery Chemistry approach.",10.1021/op034006v,2003-04-04,0.7419222178392862
Organic Process Research & Development,An Improved Synthesis of Antiulcerative Drug: Tenatoprazole,"An efficient, cost-effective and multikilogram-scale process for the synthesis of tenatoprazole 1, an antiulcerative drug, is described. The key steps in this synthesis involve the coupling of 2-mercapto-5-methoxyimidazo[4,5- b ]pyridine 2 with 2-chloromethyl-4-methoxy-3,5-dimethyl pyridine hydrochloride 3 to yield 4 and its subsequent oxidation with m -CPBA to produce sulfoxide 1 . The process has been scaled up for the multikilogram-scale of compound 1 with an overall yield of 72%. The new process requires no purification process and affords the target compound 1 with 99.8% purity by HPLC.",10.1021/op800173u,2008-11-12,0.7418336201657666
European Journal of Organic Chemistry,A Chiron Approach to the Practical and Scalable Synthesis of the <i>β</i><sub>3</sub>‐Adrenergic Receptor Agonist Vibegron,"A practical and scalable synthesis of the β 3 ‐adrenergic receptor agonist Vibegron has been developed using a streamlined chiral‐pool approach from readily available 4‐nitro‐ D ‐phenylalanine and ( R )‐mandelic acid. The synthesis features a key acid‐catalyzed N ‐acyl iminium ion cyclization followed by a highly diastereoselective reduction, enabling efficient construction of the cis ‐2,5‐disubstituted pyrrolidine core. Final amidation with a commercially available pyrrolopyrimidine sodium salt furnished Vibegron in excellent overall yield.",10.1002/ejoc.202500469,2025-06-24,0.7418318307564692
Synthesis,A Short and Efficient Synthesis of 3-{2-[2-(Bromomethyl)thiazol-4-yl]-ethynyl}-5-fluorobenzonitrile: A Precursor for PET Radioligand [18F]SP203,"An improved synthesis of 3-{2-[2-(bromomethyl)thia­zol-4-yl]ethynyl}-5-fluorobenzonitrile, a precursor for PET radioligand [¹8F]SP203, is described, wherein a new synthon was employed for Sonogashira coupling with 3-bromo-5-fluorobenzonitrile. The new five-step synthesis provided the title compound in 56% overall yield starting from 4-bromo-2-formylthiazole.",10.1055/s-0029-1216787,2009-04-30,0.7416192958971393
Synthesis,New Synthetic Route to 2-(Diethylphosphono)-2<i>H-</i>Azirines,Synthesis of new 2-substituted-2-(diethylphosphono)-3-isopropenyl-2H-azirines is described by aconvenient and efficient procedure starting from phosphorylated allenes.,10.1055/s-2002-33923,2002-09-09,0.741453166255781
Organic Process Research & Development,Practical and Efficient Approach to the Preparation of Diquafosol Tetrasodium,A scalable and practical route to synthesize the P2Y2 receptor agonist diquafosol tetrasodium has been described. Diquafosol tetrasodium was obtained via a four-step process starting from commercially available 5′-uridylic acid disodium salt. The whole procedure gives the target product in a 45% overall yield with high purity (>99%). Key steps in this process including isolation of impurities and the target product by using anion-exchange resin are discussed in detail. The optimized process has been successfully demonstrated on a large scale to support the development of diquafosol tetrasodium in China.,10.1021/acs.oprd.0c00209,2020-06-30,0.7414060319807994
Synlett,An Efficient Synthesis of a Highly Functionalized Dihydrobenzothiophene Derivative: A Ring-Contracted Analogue of the Anti-inflammatory Drug Propoxicam,"Abstract A five-step route to a ring-contracted analogue of the oxicam derivative propoxicam from thiosalicylic acid, sarcosine and N,N-dimethyl-1,3-propanediamine is described. The route has as key steps the base-promoted cross-Claisen coupling of protected sarcosine and thiosalicylic acid derivatives, the installation of a β-ketoamide moiety and a final Hg(II)-induced cyclization that creates the C–S bond of the benzothiophen-3-one core.",10.1055/a-1873-4473,2022-06-10,0.7414034745384918
Organic Process Research & Development,Facile and Cost-Effective Route for the Synthesis of Simmerafil,"An improved synthesis of simmerafil, a potent PDE5 inhibitor as a clinical candidate, is described with a 38.1% overall yield and 99.7% purity. Starting from the safe and inexpensive salicylamide ( 15 ), the key intermediate 2-propoxybenzimidamide ( 21 ), which is also a potential precursor for the preparation of pyrimidinone derivatives, was effectively and conveniently obtained. The subsequent process from 21 to simmerafil was optimized, which makes it more amenable to scale-up.",10.1021/acs.oprd.1c00184,2021-10-19,0.7413560454084036
Angewandte Chemie International Edition,The Total Synthesis of Heliquinomycinone,"A strategy for the synthesis of heliquinomycin, a selective helicase inhibitor, hinges on the spirocyclization of precursor 3. Naphthofuran 1 and aldehyde 2 were readily prepared and used in the synthesis of 3. The key steps in the total synthesis of heliquinomycinone (4) include the regioselective dihydroxylation of 3, and a novel spirocyclization under Mitsunobu conditions.",10.1002/1521-3773(20011217)40:24<4713::aid-anie4713>3.0.co;2-n,2001-12-17,0.7412582316764733
Tetrahedron,Organocatalytic route to enantioselective synthesis of ceramide trafficking inhibitor HPA-12,,10.1016/j.tetlet.2016.04.087,2016-04-30,0.7409354005615985
Organic Process Research & Development,Selection of an Enantioselective Process for the Preparation of a CGRP Receptor Inhibitor,"( R )- N- (3-(7-Methyl-1 H -indazol-5-yl)-1-(4-(1-methylpiperidin-4-yl)piperazine-1-yl)-1-oxopropan-2-yl)-4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carboxamide ( 1 ) is a potent calcitonin gene-related peptide (CGRP) receptor antagonist. We have developed a convergent, stereoselective, and economical synthesis of the hydrochloride salt of 1 and demonstrated the synthesis on a multikilogram scale. Two different routes to the chiral indazolyl amino ester subunit were developed utilizing either a Rh-catalyzed asymmetric hydrogenation or a biocatalytic process to install the single chiral center. The advantages and disadvantages of each of these process routes are discussed, as are challenges addressed in the assembly of the final drug substance.",10.1021/op3003097,2012-11-14,0.7405037423352742
Tetrahedron,An improved route to steganone,,10.1016/s0040-4039(01)86784-8,1979-01-01,0.7404743575866161
Journal of Organic Chemistry,Stereoselective Synthesis of a Dipyridyl Transient Receptor Potential Vanilloid-3 (TRPV3) Antagonist,"An efficient asymmetric synthesis of dipyridyl TRPV3 antagonist 1 is reported. The four-step route involves two C-C bond-forming steps, a highly diastereoselective alkene hydration, and asymmetric ketone hydrosilylation in 97% ee.",10.1021/acs.joc.6b02443,2016-11-04,0.7399072085238129
Organic Process Research & Development,Process Development of a CRF<sub>1</sub>Receptor Antagonist Based on the Selective Chlorination of a Benzimidazolone via Chlorine Migration,"A practical synthesis of 4-chloro-2-(2,4-dichloro-6-methylphenoxy)-1-methyl-7-(pentan-3-yl)-1 H -benzo[ d ]imidazole 1, a novel corticotropin-releasing factor 1 (CRF 1 ) receptor antagonist, has been developed. The key chemical transformations were (1) a novel regioselective chlorination at the 4-position of a benzimidazolone intermediate with 1,3,5-trichloro-1,3,5-triazinane-2,4,6-trione in the presence of sodium tertiary butoxide via a chlorine migration mechanism ( N -3 to C -4) and (2) a one-pot, three-step dehydroxylation sequence (dehydration, isomerization, and hydrogenation) of a benzylic tertiary alcohol in the presence of p -toluenesulfonic acid and a Pd catalyst. The endgame was also optimized for quality and yield improvement. The chromatography-free six-step process starting from a commercially available material afforded 1 in 35% overall yield and greater than 99% purity.",10.1021/acs.oprd.6b00389,2017-01-12,0.7398496642462611
Journal of the American Chemical Society,"A Short Synthetic Route to (+)-Austamide, (+)-Deoxyisoaustamide, and (+)-Hydratoaustamide from a Common Precursor by a Novel Palladium-Mediated Indole → Dihydroindoloazocine Cyclization","The first synthesis of (+)-austamide (1), (+)-deoxyisoaustamide (2), and (+)-hydratoaustamide (10) by a very direct route is described (Scheme 1). Starting from tryptophan methyl ester (3) intermediate 5 is generated in two steps in >98% overall yield. The key step in the synthesis is a novel cyclization of 5 involving organopalladium intermediates which gives the dihydroazocine 6. From this key intermediate the target structures are accessible in just a few steps as shown in Scheme 1. The remarkable conversion of 5 --> 6 can be rationalized by the mechanistic pathway shown in Scheme 2 that involves a multistep sequence which includes palladation, cyclization, and rearrangement.",10.1021/ja026663t,2002-06-14,0.7395145522608616
Organic Process Research & Development,Development of an Efficient and Scalable Asymmetric Synthesis of Eliglustat via Ruthenium(II)-Catalyzed Asymmetric Transfer Hydrogenation,"An efficient and scalable synthesis of eliglustat ( 1 ) is herein reported. This novel route features a three-step telescoped process to afford the α-dibenzylamino β-ketoester 6 in 85% overall yield from commercially available 1,4-benzodioxane-6-carboxylic acid 7 . The key intermediate 5 was obtained via an efficient ruthenium-catalyzed DKR-ATH reaction, which afforded the desired product in 90% isolated yield with >99:1 dr and 99.7% ee on a 100 g scale. In addition, the amidation of sterically hindered carboxylic acid 14 was optimized and amenable to scale-up. This process not only gives a desirable total yield but also avoids hazardous conditions and chromatographic purification. The robustness of this synthesis was successfully performed on a multigram scale to afford 1 with >99.9% de and >99.9% ee in 56.8% overall yield in nine steps.",10.1021/acs.oprd.9b00138,2019-05-23,0.7394990627297097
Organic Letters,"Synthesis of Verubecestat, a BACE1 Inhibitor for the Treatment of Alzheimer’s Disease","Verubecestat is an inhibitor of β-secretase being evaluated for the treatment of Alzheimer's disease. The first-generation route relies on an amide coupling with a functionalized aniline, the preparation of which introduces synthetic inefficiencies. The second-generation route replaces this with a copper-catalyzed C-N coupling, allowing for more direct access to the target. Other features of the new route include a diastereoselective Mannich-type addition into an Ellman sulfinyl ketimine and a late-stage guanidinylation.",10.1021/acs.orglett.6b01793,2016-11-04,0.7393783159307715
Organic Process Research & Development,"Practical, Highly Convergent, Asymmetric Synthesis of a Selective PPARγ Modulator","A practical, highly convergent, asymmetric synthesis of a selective PPARγ modulator 1 is described. The inhibitor contains two key components, a 6-trifluoromethoxy-3-acylindole ( 6 ) and ( R )-α-aryloxybutanoic acid derivative ( 10 ). Two methods were developed to overcome the regioselectivity issues encountered in the preparation of the 6-substituted indole. The first involved an intramolecular Heck reaction of an iodoaryl enamine. The second involved application of a catalytic Meerwein arylation reaction between 2-nitro-4-trifluoromethoxyaniline and isopropenyl acetate and subsequent reductive cyclization. The α-aryloxybutanoic acid was prepared via an asymmetric hydrogenation of the corresponding α-aryloxy-α,β-unsaturated acid. Tetrabutylammonium iodide-catalyzed coupling of the two fragments and ester hydrolysis completed the convergent synthesis. The described convergent synthesis was used to prepare >3 kg of drug substance 1 in 50% overall yield and with >99.5% ee.",10.1021/op8002882,2009-03-09,0.7393753466125983
Synlett,Synthetic Studies on Azaspiracid: Synthesis of Key Intermediate for the Construction of the FGHI Ring System,"A highly stereoselective and convergent approach for the key intermediate of the FGHI ring system of azaspiracid is ­described. The synthesis features the desymmetrization strategy for the construction of the C27-C33 fragment, Masamune-Roush coupling conditions for the C33-C34 bond formation, and Sharpless asymmetric dihydroxylation as the key steps. One more important feature of this synthetic route is that we can synthesize other ­enantiomers of the FGHI ring system by changing asymmetric ­hydroboration conditions and valerolactone.",10.1055/s-2007-985585,2007-08-14,0.739310431859648
Organic Letters,Improved Total Synthesis of the Potent HDAC Inhibitor FK228 (FR-901228),A scaleable synthesis of the potent histone deacetylase (HDAC) inhibitor FK228 is described. A reliable strategy for preparing the key beta-hydroxy mercapto heptenoic acid partner was accomplished in nine steps and 13% overall yield. A Noyori asymmetric hydrogen-transfer reaction established the hydroxyl stereochemistry in >99:1 er via the reduction of a propargylic ketone.,10.1021/ol702957z,2008-01-19,0.7392424820746568
Tetrahedron,Enantioselective intramolecular CH insertion route to a key intermediate for the synthesis of trinem antibiotics,,10.1016/s0040-4039(98)02055-3,1998-12-01,0.739168900998362
Journal of Organic Chemistry,An Improved Asymmetric Synthesis of Malyngamide U and Its 2′-Epimer,"An accelerated and improved asymmetric synthesis of malyngamide U (1) and its 2'-epimer (2'-epi-1) was accomplished from readily available n-hexanal, ethanolamine and (R)-(-)-carvone. The key steps involved a Johnson-Claisen rearrangement in the synthesis of an unsaturated carboxylic acid 4 and an aldol reaction in the construction of the skeleton of 1 and 2'-epi-1. There are 13 steps in the synthesis, with a 2.7% overall yield for 1 and a 0.4% yield for 2'-epi-1.",10.1021/jo800876u,2008-07-26,0.7389535093965989
Organic Process Research & Development,Practical Asymmetric Hydrogenation-Based Synthesis of a Class-Selective Histone Deacetylase Inhibitor,"Two syntheses of the class-selective histone deacetylase inhibitor 1 are reported. In the first, eight-step entailing synthesis, the key transformations were a highly efficient [3 + 2] dipolar cycloaddition affording trans - rac - 5 and its resolution. In the second, asymmetric approach, the key steps were a highly selective asymmetric hydrogenation to produce the cis -( S,S )-3,4-disubstituted pyrrolidine 18 followed by an amide formation with simultaneous chiral inversion of the carboxy stereocenter to generate the key intermediate trans -( R,S )-3,4-disubstituted pyrrolidine 19 . The overall yield increased from ∼6% for the resolution approach to ∼26% for the enantioselective approach.",10.1021/op500250b,2014-10-29,0.7388344240435445
Organic Process Research & Development,"A Practical Synthesis of the PDE4 Inhibitor, KW-4490",A practical and scalable synthesis of a PDE4 inhibitor KW-4490 ( 1 ) was developed. This improved synthesis features the construction of the 1-arylcyclohexene ( 9 ) by the Diels−Alder reaction followed by a newly established Brønsted acid-promoted hydrocyanation. Subsequent crystallization-induced dynamic resolution enabled the high-yield production of the desired cis -isomer ( cis-8 ). The synthesis was achieved in seven steps in 37% overall yield.,10.1021/op1001287,2010-07-08,0.7386237544921492
Journal of Organic Chemistry,An Enantioselective Synthesis of Tarchonanthuslactone,An enantioselective synthesis of tarchonanthuslactone has been achieved in eight steps from ethyl sorbate. The asymmetry of the route was introduced via a Sharpless asymmetric dihydroxylation allowing access to either enantiomer. The synthesis utilizes a palladium-catalyzed reduction and a diastereoselective base-catalyzed acetal formation as the key steps. The pyran ring of tarchonanthuslactone was established by a Still-olefination/lactonization sequence. DCC-mediated attachment of dihydrocaffeic acid completed the synthesis of tarchonanthuslactone in a 19% overall yield.,10.1021/jo0163400,2002-03-23,0.7385654364286869
Organic Process Research & Development,Improved Synthesis of 6-Chloro-5-methylpyridin-2-amine: A Key Intermediate for Making Lumacaftor,"A safe and efficient synthesis of 6-chloro-5-methylpyridin-2-amine, a key intermediate for lumacaftor, is described, which avoids the utilization of peroxide. In this four-step sequence, starting from 2-amino-6-chloropyridine, the crucial 5-position methylation was achieved via a Suzuki-Miyaura cross-coupling reaction. By adopting this synthetic route, 6-chloro-5-methylpyridin-2-amine was produced on a hectogram scale with 62.4% overall yield and 99.49% purity.",10.1021/acs.oprd.9b00556,2020-04-24,0.7382421009481653
Organic Process Research & Development,Development of an Improved Route for the Synthesis of an Abemaciclib Intermediate,"A new synthesis for an intermediate of abemaciclib is described. Keys to this route are the use of inexpensive starting materials, biphasic amine alkylation for mild C–N bond formation, anhydrous coupling of a 2-chloropyridine derivative with LiHMDS to avoid a hydroxy impurity, and neutral, fluoride-free conditions to affect desilylation. Scale-up of the optimized conditions are described on a kilogram scale.",10.1021/acs.oprd.9b00347,2019-10-23,0.7380982445575474
Organic Process Research & Development,Development of an Efficient and Practical Route for the Multikilogram Manufacture of the SRC Kinase Inhibitor AZD0530,"In a previous publication ( Org. Process Res. Dev. 2010, 14, DOI: 10.1021/op100161y ) we described the process research and development of a manufacturing route for the potent SRC kinase inhibitor AZD0530. While the route was successfully used to manufacture 4.5 kg of AZD0530 difumarate, it was still relatively long, used two Mitsunobu couplings, and was, in our opinion, undesirable for manufacture on a larger scale. Herein we describe the research and development of a shorter, more practical synthesis of AZD0530 difumarate. The new route, which required fewer steps, scaled well to produce >80 kg of AZD0530 difumarate in an overall yield of 38%.",10.1021/op100163m,2010-08-23,0.7380126209516581
Organic Process Research & Development,"A Facile and Scaleable Synthesis of ABT-239, A Benzofuranoid H<sub>3</sub> Antagonist","A facile and scaleable synthesis of a potent and selective histamine H 3 receptor antagonist, ABT-239 ( 1 ), was developed starting from commercially available 4‘-hydroxy-biphenyl-4-carbonitrile ( 2 ). The synthesis comprised four chemical steps and a salt formation step with an overall yield of 40%. A highly selective monoiodination of a phenol was developed and used to prepare iodophenol ( 3b ) in near quantitative yield using NIS in AcOH in the presence of a small amount of H 2 SO 4 . A Pd-catalyzed cross coupling reaction of the iodophenols ( 3b ) with butyn-3-ol ( 4a ) provided benzofuran ( 5 ) in one step in >80% yield, en route to 1 . The new process required no chromatographic purification throughout the synthesis and was successfully demonstrated on scale-up to prepare 1.7 kg of the target ABT-239 ( 1 ).",10.1021/op049809c,2004-12-21,0.7377003906726246
Organic Process Research & Development,Development of a Scalable Alkylation via a Protection/Deprotection Sequence for BMT-773752: Key Intermediate in the Synthetic Route to Repotrectinib,"The development of a practical and scalable synthetic route to BMT-773752-02, a key starting material for repotrectinib, is described. The original sequence exhibited various limitations such as use of pyrophoric organolithium reagents, low yield, poor diastereoselectivity, and lengthy workup/purification procedures, which were overcome by development of a new route. A salt screening was conducted to improve the physical properties of the title compound. The scalability of the newly designed synthetic strategy has been demonstrated on multihundred-kilogram scale production to afford greater than a metric ton of this intermediate.",10.1021/acs.oprd.4c00061,2024-05-08,0.7376894794385211
Organic Process Research & Development,"Scalable Synthesis of Lunresertib, a Selective PKMYT1 Inhibitor","PKMYT1 is a regulator of CDK1 phosphorylation and is a compelling therapeutic target for the treatment of certain types of DNA damage response cancers due to its established synthetic lethal relationship with CCNE1 amplification. Lunresertib is the first PKMYT1 inhibitor to enter clinical trials for the treatment of various solid tumors. We hereby describe the process development of an efficient, robust, and scalable synthetic route that allows the rapid production of large quantities of lunresertib drug substance (RP-6306). The synthesis features two Pd-mediated couplings, a novel chiral resolution of atropisomers, a one-pot hydration/demethylation sequence, and a recrystallization that upgrades enantiomeric purity. Screening and optimization of the resolution and reactions and control of impurities are discussed.",10.1021/acs.oprd.4c00493,2025-06-27,0.7376744068230665
Organic Process Research & Development,"Development of a Scalable Synthetic Route to (1 <i>R</i> ,5 <i>R</i> )-2,2-Dimethoxybicyclo[3.1.0]hexan-3-one: An Important Intermediate in the Synthesis of Lenacapavir","High Resolution Image Download MS PowerPoint Slide (1 R,5 R )-2,2-Dimethoxybicyclo[3.1.0]hexan-3-one is used in the asymmetric synthesis of lenacapavir. Herein, we report an enantioselective synthesis of this important chiral intermediate from the inexpensive commodity ( R )-epichlorohydrin. This synthetic method comprises 6 steps, including a 4-step telescoped bicyclic ketone synthesis, I 2 -promoted hydroxylation, and an Albright–Goldman oxidation. This sequence affords (1 R,5 R )-2,2-dimethoxybicyclo[3.1.0]hexan-3-one in an overall 25% isolated yield as an enantiomerically pure compound. The entire process has been successfully demonstrated on a hundred-gram scale.",10.1021/acs.oprd.4c00527,2025-02-26,0.7374941730463517
Tetrahedron,An efficient and flexible route to novel triazolopiperazine scaffolds,,10.1016/j.tetlet.2020.152600,2020-10-29,0.7371904110191674
Organic Process Research & Development,Process Research Towards a Scalable Synthesis of the Muscarinic M<sub>1</sub> Receptor Subtype Selective Agonist MCD-386,"An efficient process for the M 1 -selective muscarinic agonist MCD-386 has been developed that offers significant advantages over the original synthetic approach. The new process utilizes an improved preparation of a known symmetrical diamine ester, followed by elaboration to a symmetrical 5-substituted tetrahydropyrimidine. The new route avoids cryogenics and chromatography steps, circumvents an expensive protecting group strategy, and offers significant improvements in cost and throughput.",10.1021/op2001996,2011-09-11,0.7371633467307316
Journal of Organic Chemistry,Phosphate Tether-Mediated Approach to the Formal Total Synthesis of (−)-Salicylihalamides A and B,"A concise formal synthesis of the cytotoxic macrolides (-)-salicylihalamides A and B is reported. Key features of the synthetic strategy include a chemoselective hydroboration, highly regio- and diastereoselective methyl cuprate addition, Pd-catalyzed formate reduction, and an E-selective ring-closing metathesis to construct the 12-membered macrocycle subunit. Overall, two routes have been developed from a readily prepared bicyclic phosphate (4 steps), a 13-step route and a more efficient 9-step sequence relying on regioselective esterification of a key diol.",10.1021/jo200337v,2011-04-19,0.7370510197834726
Organic Process Research & Development,Development of a Manufacturing Process for S-892216 Part I: A Novel Method for Constructing a Multi-Substituted Barbiturate Skeleton for Scalable Synthesis,"S-892216, a second-generation 3CL protease inhibitor, is currently being developed as a clinical drug candidate for the treatment of SARS-CoV-2 infection. This paper outlines the development process and scaling-up of S-892216 for early-phase clinical trials. The developed synthetic route involved a condensation reaction between carboxylic acids and urea with T3P, followed by cyclization in the presence of CDI and DBU to construct a barbiturate core. This novel method facilitated the efficient production of high-quality S-892216 in six steps, with an overall yield of 41.3% from readily available starting materials.",10.1021/acs.oprd.5c00071,2025-05-20,0.7367474481331233
Organic Process Research & Development,"Use of Lipase Catalytic Resolution in the Preparation of Ethyl (2<i>S</i>,5<i>R</i>)-5-((Benzyloxy)amino)piperidine-2-carboxylate, a Key Intermediate of the β-Lactamase Inhibitor Avibactam","Here we describe an efficient and cost-effective chemoenzymatic synthesis of the β-lactamase inhibitor avibactam starting from commercially available ethyl 5-hydroxypicolinate hydrochloride. Avibactam was synthesized in 10 steps with an overall yield of 23.9%. The synthetic route features a novel lipase-catalyzed resolution step during the preparation of (2 S,5 S )-ethyl 5-hydroxypiperidine-2-carboxylate, a valuable precursor of the key intermediate ethyl (2 S,5 R )-5-((benzyloxy)amino)piperidine-2-carboxylate. Our synthetic route was used to produce 400 g of avibactam sodium salt.",10.1021/acs.oprd.8b00173,2018-11-05,0.7366938266764204
Organic Process Research & Development,Development of an Efficient Palladium-Catalyzed Intramolecular Carbometalation Reaction for the Synthesis of a Dibenzoxapine Containing Tetra-substituted Exocyclic Alkene,"A practical and scaleable synthesis of ( Z )-3-(1-(8-bromodibenzo[ b, e ]oxepin-11(6 H )-ylidene)ethyl)aniline hydrochloride ( 1 · HCl ), a key intermediate in the synthesis of a selective nuclear hormone receptor modulator, is described. The target compound is prepared in five steps from commercially available (5-bromo-2-iodophenyl)methanol ( 5 ) with a 47% overall yield. The key step involves a palladium-catalyzed intramolecular carbometalation of an alkyne, which affords the dibenzoxapine containing tetrasubstituted exocyclic alkene framework stereoselectively in a single step from readily available building blocks 4-bromo-2-(2-iodo-phenoxymethyl)-1-prop-1-ynyl-benzene ( 3 ) and 3-nitrophenylboronic acid ( 4 ). The development of each step is described. The main focus of the paper is the description and optimization of the intramolecular carbometalation of an alkyne. Eventually, the target compound 1 · HCl was prepared in multikilogram quantities with >97% purity.",10.1021/op800231b,2008-12-30,0.7364703579730149
Organic Process Research & Development,Practical Synthesis of a S1P Receptor 1 Agonist via a Guareschi–Thorpe Reaction,"A practical synthesis of S1P receptor 1 agonist ACT-334441 ( 1 ) through late-stage convergent coupling of two key intermediates is described. The first intermediate is 2-cyclopentyl-6-methoxyisonicotinic acid whose skeleton was built from 1-cyclopentylethanone, ethyl oxalate, and cyanoacetate in a Guareschi–Thorpe reaction in 42% yield over five steps. The second, chiral intermediate, is a phenol ether derived from enantiomerically pure ( R )-isopropylidene glycerol (( R )-solketal) and 3-ethyl-4-hydroxy-5-methylbenzonitrile in 71% yield in a one-pot reaction. The overall sequence entails 18 chemical steps with 10 isolated intermediates. All raw materials are cheap and readily available in bulk quantities, the reaction conditions match with standard pilot plant equipment, and the route reproducibly afforded 3–20 kg of 1 in excellent purity and yield for clinical studies.",10.1021/acs.oprd.6b00210,2016-08-17,0.7359086919232012
Organic Letters,Facile Entry to an Efficient and Practical Enantioselective Synthesis of a Polycyclic Cholesteryl Ester Transfer Protein Inhibitor,"An efficient enantioselective synthesis of the chiral polycyclic cholesteryl ester transfer protein (CETP) inhibitor 1 has been developed. The synthesis was rendered practical for large scale via the development of a modified Hantzsch-type reaction to prepare the sterically hindered pyridine ring, enantioselective hydrogenation of hindered ketone 6 utilizing novel BIBOP-amino-pyridine derived Ru complex, efficient ICl promoted lactone formation, and a BF3 mediated hydrogenation process for diastereoselective lactol reduction. This efficient route was successfully scaled to produce multikilogram quantities of challenging CETP drug candidate 1.",10.1021/ol501833g,2014-08-01,0.7358859788304951
Organic Letters,Alectinib Synthesis through Formal α-Arylation of Enone,"A new synthetic route for the synthesis of Alectinib, which is used as an adjuvant and first line of treatment in ALK-positive non-small cell lung cancer, is reported. The developed route starts from readily available starting materials (4-(4-methoxyphenyl)butyric acid or 2-ethyl anisole) and employs Suzuki-Miyaura cross-coupling and reductive cyclization as key steps. Good yield and no regioisomeric mixture formation are the key highlights of this route.",10.1021/acs.orglett.5c03186,2025-08-24,0.7358337278193399
Tetrahedron,Synthesis of heterocycles-1. One step synthesis of acetylthiadiazolines,,10.1016/s0040-4039(01)86092-5,1979-01-01,0.7356596073681481
Organic Process Research & Development,"Scalable Process for Making 5,7-Dichlorotetrahydroisoquinoline-6-carboxylic Acid Using Methylene as the Protecting Group","The development of an industrially scalable synthetic route for 5,7-dichlorotetrahydroisoquinoline-6-carboxylic acid ( 1 ), a key starting material for lifitegrast, is described. This route includes the following features: (1) tetrahydroisoquinoline 19 was prepared in three steps from readily commercially available 3,5-dichlorobenzoyl chloride and 2-aminoethanol in a high total yield of 76%; (2) formaldehyde instead of triphenylmethyl chloride was employed in the protection of the secondary amine, resulting in much higher atom economy; (3) the target compound 1 was produced in an overall yield of 66% with an HPLC purity of 99% by area.",10.1021/acs.oprd.1c00229,2021-10-19,0.735559060944857
Organic Process Research & Development,Selection and Development of the Manufacturing Route for EP<sub>1</sub> Antagonist GSK269984B,"A potential manufacturing route for the EP 1 antagonist GSK269984B was developed. Four synthetic approaches were examined, and a successful realisation of each is presented. The rationale supporting selection of the preferred route is discussed. This route utilised a phenolic aldol reaction as the key step and relied on selective hydrogenolysis to reduce an intermediate diarylmethanol. Further optimisation of the selected route is presented, delivering GSK269984B in three stages and 46% overall yield from readily available starting materials.",10.1021/op100072y,2010-06-21,0.7354105872012003
Organic Process Research & Development,Development of Scalable Syntheses of Selective PI3K inhibitors,"On the basis of a more practical and scalable route to an iodothiophene, an efficient and reliable synthesis has been developed for three selective PI3K inhibitors. From this advanced intermediate, the three title compounds were each prepared in five additional steps. Key learnings also include: high throughput experimentation (HTE) screening toward a more robust Suzuki coupling, a more efficient triazole synthesis, and an acid/base cleanup developed to purify the final compounds. The final enabled synthesis required no column chromatography.",10.1021/op100286g,2011-03-11,0.735355379444568
Tetrahedron,"Stereoselective synthesis of methyl branched chiral deoxypropionate units: a new route for synthesis of insect pheromone (−)-lardolure and (2R,4R,6R,8R) 2,4,6,8-tetramethylundecanoic acid",,10.1016/j.tetlet.2012.08.112,2012-09-04,0.7352078700371774
Tetrahedron,"A new and efficient route for 1,3,3′-triketones",,10.1016/s0040-4039(01)01654-9,2001-10-01,0.7351672315649836
Tetrahedron,"A new and efficient route to 3-(1,1-dimethylallyl)coumarins",,10.1016/s0040-4039(00)79724-3,1991-07-01,0.7351672315649836
Synthesis,Practical Synthesis of 2-(2-Isopropylaminothiazol-4-yl)-7-methoxy-1<i>H</i>-quinolin-4-one: Key Intermediate for the Synthesis of Potent HCV NS3 Protease Inhibitor BILN 2061,"Herein we describe the development of an efficient, safe and practical process for the synthesis of 7-methoxy-2-(2-amino-4-thiazolyl)quinoline. Our new process allowed for a more convergent approach and eliminates the use of potentially dangerous reagents such as diazomethane used in the previous discovery approach.",10.1055/s-2006-942472,2006-07-25,0.7350129955259025
Organic Process Research & Development,Convergent Asymmetric Synthesis of a Renin Inhibitor: A Highly Efficient Construction Method of Three Stereogenic Centers,"An improved asymmetric synthesis of renin inhibitor DS-8108b (1) is described. This compound consists of three intermediates: 4-aminoadamantan-1-ol, ketopiperazine, and chiral lactone which contains three stereogenic centers. Especially, the chiral lactone is a key intermediate, and development of a scalable synthetic method was required, considering the quality, speed, and manufacturing cost. We established a scalable synthetic method of 1 from 4,6- O -benzylidene- d -glucose for early clinical studies. Furthermore, a highly efficient synthetic route of the chiral lactone for manufacturing was also successfully developed from n- butyryl chloride via Evans stereoselective alkylation, followed by stereoselective bromolactonization. In addition, a unique and highly efficient conversion protocol was developed from α-bromo- N -(2-nitrobenzenesulfonyl)amide to apparent rearranged diamine derivatives with a sequential aziridination–substitution reaction in one-pot.",10.1021/op400219y,2013-10-17,0.7348842200345003
Synthesis,A Practical Three-Step Synthesis of Vinylferrocene,"An improved, short and efficient synthesis of vinylferrocene is reported. This three-step synthesis includes Friedel–Crafts acylation, reduction, and a one-pot mesylation/elimination step to afford the target compound in 62% yield over three steps.",10.1055/s-0036-1589142,2017-12-11,0.7348232068221168
Journal of Organic Chemistry,Concise Formal Synthesis of the Bryostatin Southern Hemisphere (C17−C27),An efficient synthesis of Hale and co-workers' C17-C27 bryostatin southern hemisphere intermediate has been accomplished in six steps and 33% overall yield from (R)-2-(benzyloxy)propanal. The synthesis features a one-pot DIBALH/HWE ester homologation as well as a novel acetonide rearrangement/glycal formation cascade.,10.1021/jo0495081,2004-05-20,0.734753646880245
Organic Process Research & Development,"A Simplified Process for the Manufacture of Imagabalin Hydrochloride (PD-0332334), an α2δ-Ligand for the Treatment of Generalised Anxiety Disorder","The development of a highly efficient two-step process for the manufacture of the α2δ-ligand imagabalin hydrochloride 1 is described in 50% overall yield from ( R )-3-methylhexanoic acid 2 . Key aspects of this route include the development of a one-pot process for the synthesis of β-enamine ester 7 and its subsequent diastereoselective hydrogenation with a Ru-( S )-BINAP catalyst. The use of a combination of TFA, ammonium trifluoroacetate, and relatively low pressures in the asymmetric hydrogenation are novel conditions reported for this type of transformation. The simplified process described realised a 4-fold reduction in cost of goods compared with the previously described enabling route.",10.1021/op2002326,2011-10-11,0.734742975263467
Tetrahedron,"Synthesis of the (9S,18R)-seco acid of the leukocyte adhesion inhibitor cyclamenol A",,10.1016/s0040-4039(99)02135-8,2000-01-01,0.7346995994329376
Tetrahedron,A novel and efficient synthesis of the key intermediate of 1β-methylcarbapenem antibiotics from ()-methyl 3-hydroxy-2-methylpropionate,,10.1016/s0040-4039(00)85442-8,1986-01-01,0.7345631994379065
Journal of Organic Chemistry,Total Synthesis of Hapalindoles J and U,"The total synthesis of D,L-hapalindoles J and U has been accomplished. Hapalindole J was prepared in 11% overall yield over 11 synthetic steps and hapalindole U was prepared in 25% overall yield over 13 synthetic steps from commercially available materials. The route employs a novel silyl ether-based strategy for accessing the 6:5:6:6 ring system of the hapalindoles rapidly and in good yields.",10.1021/jo202139k,2011-11-29,0.7344673204197718
Synlett,"Total Synthesis of Denigrins D and E, and Formal Synthesis of Polycitones A and B","Abstract We report here the concise total syntheses of the densely substituted pyrrole-containing, marine-derived alkaloids denigrins E and D, together with the formal syntheses of polycitones A and B. Starting from p-methoxydibenzyl ketone, denigrin E was obtained in just two steps (44% overall yield), while denigrin D was synthesized in three steps (26% overall yield). In addition, the Steglich synthon, a key intermediate toward polycitones A and B, was accessed in three steps (34% overall yield), thus completing the formal synthesis of polycitones A and B. The overall efficiency of this route arises from the key transformation: a microwave-assisted Paal–Knorr pyrrole synthesis.",10.1055/a-2736-0204,2025-11-18,0.7344379592824894
Synthesis,A Non-infringing Route for Enantioselective Synthesis of Antiepileptic Agent Lacosamide,A non-infringing route for enantioselective synthesis of lacosamide has been developed. The synthesis started from commercially available acrylic acid and was completed in eight steps using Sharpless asymmetric dihydroxylation as a key step with an overall yield of 29%. All the reactions were very clean with good yields.,10.1055/s-0033-1339901,2013-10-02,0.7343050186468031
Journal of Organic Chemistry,"A Scalable Synthesis of an Azabicyclooctanyl Derivative, a Novel DPP-4 Inhibitor","A practical synthetic strategy to a chiral azabicycclooctanyl derivative (1), a potent DPP-4 inhibitor, starting from a commercially available nortropine is described. The stereogenic center of 1 was established employing a modified protocol of Ellman's diastereoselective addition of a benzylic nucleophile to tert-butanesulfinimine. Other key steps include Corey-Chaykovsky reaction, Meinwald rearrangement, and CDMT-promoted amide bond formation involving a sterically hindered amine 2.",10.1021/jo801830x,2008-10-14,0.7340991256295533
Angewandte Chemie International Edition,Total Synthesis of (−)‐Melotenine A,"'Melo' out: A concise asymmetric synthesis of (−)-melotenine A has been accomplished in fourteen steps and 1 % overall yield from commercial N-tosylindole-3-carboxaldehyde. Key steps include a Piers annulation, an intermolecular vinylogous aldol reaction, and a novel one-pot sequence to prepare the ABCE tetracycle. Boc=tert-butoxycarbonyl, Ts=4-toluenesulfonyl.",10.1002/anie.201302517,2013-06-19,0.7340614770732375
Tetrahedron,The preparation of a key intermediate in the synthesis of ajaconine and atidine,,10.1016/s0040-4039(01)99066-5,1968-01-01,0.7336079878100725
Tetrahedron,Synthesis of a key intermediate for the total synthesis of streptovaricin A,,10.1016/s0040-4039(00)88703-1,1982-01-01,0.73337359215507
Organic Process Research & Development,Large-Scale Synthesis of the Glucosylceramide Synthase Inhibitor <i>N</i>-[5-(Adamantan-1-yl-methoxy)-pentyl]-1-deoxynojirimycin,"A synthetic route for the preparation of glucosylceramide synthase inhibitor N -[5-(adamantan-1-yl-methoxy)-pentyl]-1-deoxynojirimycin methanesulfonic acid salt (AMP-DNM) has been developed. Herein we report the development and optimization of this synthetic route from its initial version in an academic research laboratory at milligram-scale to the final optimized route that was implemented in a cGMP miniplant on kilogram-scale. The definitive route starts with the separate synthesis of building blocks 2,3,4,6-tetra- O -benzyl-1-deoxynojirimycin and 5-(adamantan-1-yl-methoxy)-pentanal. The aldehyde was synthesized from 1,5-pentanediol in five steps and 45% overall yield. Protected 1-deoxynojirimycin was prepared by a successive hemiacetal reduction/Swern oxidation/double reductive amination sequence of 2,3,4,5-tetra- O -benzyl- d -glucopyranose in 52% overall yield. Reductive amination of the two building blocks produced the benzyl-protected penultimate that was isolated as its crystalline (+)DTTA salt in 68% yield. Hydrogenolysis of the penultimate and crystallization of the end product as its methanesulfonic acid salt produced AMP-DNM in 76% yield with a purity of >99.5%. The described route enables the production of multikilogram amounts of inhibitor AMP-DNM as a stable crystalline solid with high purity under cGMP control.",10.1021/op700295x,2008-04-29,0.7333289342045874
Journal of the American Chemical Society,Total Synthesis of A-315675:  A Potent Inhibitor of Influenza Neuraminidase,"A concise, stereocontrolled, and practical synthesis of a neuraminidase inhibitor consisting of a highly functionalized D-proline scaffold is described. Key features involve a stereocontrolled addition of a propiolate ester to a chiral nonracemic nitrone derived originally from D-serine and the manipulation of acyclic and cyclic motifs en route to the target in 12.8% overall yield over 22 steps. Several crystalline intermediates were suitable for single-crystal X-ray analysis.",10.1021/ja0126226,2002-04-05,0.7333173189845287
Organic Process Research & Development,The Synthesis of a Novel Inhibitor of B-Raf Kinase,"A scaleable synthetic route to [4,7‘]bis-isoquinolinyl-1-yl-(2- tert -butyl-pyrimidine-5-yl)amine ( 1 ), an inhibitor of B-Raf kinase is described. The key step in the synthesis is the Pd-catalyzed Negishi coupling of 4-bromo-1-chloroisoquinoline with trifluoromethanesulfonic acid isoquinoline-7-yl ester to yield 1-chloro[4,7‘]bis-isoquinolinyl. This intermediate is transformed to the desired drug substance in one additional step, by reaction with 2- tert -butyl-5-aminopyrimidine in the presence of NaH. A special focus was put on the finally successful removal of traces of Zn and Pd in the drug substance, which came from the Negishi coupling.",10.1021/op0501601,2005-12-09,0.7332538654611438
Tetrahedron,The efficient synthesis of d-xylulose and formal synthesis of Syringolide 1,,10.1016/j.tetlet.2020.152321,2020-08-26,0.7331811954861776
Organic Process Research & Development,Development of a Practical Route for the Manufacture of <i>N</i>-[5-(3-Imidazol-1-yl-4-methanesulfonyl-phenyl)-4-methyl-thiazol-2-yl]acetamide,"An efficient synthesis of a potent candidate in our respiratory program is described. The synthesis based on a key Darzens condensation−α,β-epoxide rearrangement circumvented the toxicity and safety issues encountered in the original synthesis route. Subsequent functionalization and formation of an heterocyclic moiety is presented with a particular emphasis on the practicality, robustness, and streamlining of the process.",10.1021/op700222r,2008-01-01,0.732982301160459
Organic Process Research & Development,Practical Asymmetric Synthesis of an Edivoxetine·HCl Intermediate via an Efficient Diazotization Process,"A convergent synthesis of ( S )-(4-benzylmorpholin-2-yl)(morpholino)methanone methanesulfonate ( 1 ), a key regulatory starting material for edivoxetine·HCl, was developed at Eli Lilly & Company. This novel synthesis utilizes d -serine as the source of chirality, which is preserved throughout the synthesis. Key features include the development of a scalable diazotization process to produce ( S )-epoxy acid 7, which was optimized to improve the process safety profile. The final ( S )-morpholino acid intermediate 11 was converted to the title compound using T3P with >99.9% purity in 75% yield. Life cycle analysis of the new route revealed a 69% reduction in global warming potential (GWP) for solvent usage relative to the prior route of manufacture.",10.1021/acs.oprd.5b00014,2015-03-24,0.7328566990614004
Organic Process Research & Development,Development of a Scalable Synthesis of Gastrazole (JB95008):  A Potent CC<i>K</i><sub>2</sub> Receptor Antagonist,"A practical and scalable synthesis was developed that was used to prepare multikilogram batches of gastrazole, a selective cholecystokinin-2 receptor antagonist. In addition, evidence was found to indicate an amide bond-forming reaction proceeded via the isoimide of a benzimidazoleamide acid derivative.",10.1021/op0500638,2005-06-24,0.7328053335082517
Journal of Organic Chemistry,"Efficient Synthesis of a Trisubstituted 1,6-Naphthyridone from Acetonedicarboxylate and Regioselective Suzuki Arylation","[reaction: see text] An efficient five-step synthesis of 1,6-naphthyridone 3b, a p38 mitogen-activated protein (MAP) kinase inhibitor intermediate, in 32% overall yield starting from acetonedicarboxylate (ADC) is described. The synthesis began with a selective monoamidation of ADC dimethyl ester enolate 9. A novel concomitant enamine formation and an imide cyclization afforded the nitrogen differentially protected enamide imide 12. Treatment of 12 with KO(t)Bu and 3-ethoxyacrylate produced lactam 15 quantitatively, which was converted to tetrachloronaphthyridone 19 via a one-pot p-methoxybenzyl (PMB) deprotection and bischlorination. A highly regioselective Pd(OAc)2/IMes-catalyzed Suzuki coupling completed the synthesis.",10.1021/jo0514927,2005-11-16,0.7328009367378148
Synthesis,"A Convergent Synthesis of CGS23305, A Thromboxane Synthase Inhibitor","All articles of this category A convergent synthesis of CGS23305 was discovered. The route to the pyridine aldehyde intermediate 5 was reduced from four to two steps. The pyridine aldehyde was converted to the key pyridine aldehyde ester intermediate 7 via Miachel Addition of the N , N -diethylenamine 6 to ethyl acrylate. A Wittig alkenation using the multifunctional moiety 19 completed the carbons keleteon assembly. Hydrogenation and hydrolysis afforded CGS23305 in 44% overall yield from 14 (6 steps). convergent synthesis - pyridine - aldehydes - thromboxane inhibitor",10.1055/s-1999-3458,1999-05-01,0.7327483584615851
Journal of the American Chemical Society,"A Direct and Efficient Stereocontrolled Synthetic Route to the Pseudopterosins, Potent Marine Antiinflammatory Agents","Described herein is a new synthetic route to pseudopterosin aglycone ( 3 ), a key intermediate for the synthesis of a group of antiinflammatory natural products including pseudopterosin A ( 1 ) and E ( 2 ). The pathway of synthesis starts with the abundant and inexpensive ( S )-(−)-limonene and its long-known cyclic hydroboration product ( 4 ) and leads to the chiral hydroxy ketone 6 . Conversion of 6 to 10 followed by a novel aromatic annulation produced 15 which underwent a highly diastereoselective cyclization to afford the protected pseudopterosin aglycone 16 . The naturally occurring pseudopterosins such as 1 and 2 are readily available from this key intermediate.",10.1021/ja983041s,1998-11-17,0.7327441148917004
Journal of Organic Chemistry,Asymmetric Formal Synthesis of the Long-Acting DPP-4 Inhibitor Omarigliptin,A highly efficient asymmetric synthesis of the key tetrahydropyranol intermediate of DPP-4 inhibitor omarigliptin (1) is described. The successful development of a protecting-group- and precious-metal-free synthesis was achieved via the discovery of a practical asymmetric Henry reaction and the application of a one-pot nitro-Michael-lactolization-dehydration through-process. Other features of the synthesis include a highly efficient MsCl-mediated dehydration and a crystallization-induced dynamic resolution for exceptional ee and dr upgrade. The synthesis of this complex intermediate utilizes simple starting materials and proceeds in four linear steps.,10.1021/acs.joc.7b01467,2017-08-04,0.7327179333123356
Organic Process Research & Development,"Efficient Multikilogram-Scale Synthesis of PTDSS1 Inhibitor: Development of a Practical and Scalable Optical Resolution Method for Chiral 2,3-Pyrrolidinedione","DS55980254 ( 1 ) is a potent and selective phosphatidylserine synthase 1 (PTDSS1) inhibitor discovered by Daiichi Sankyo. We have developed a practical and unique optical resolution method using a chiral amine for 2,3-pyrrolidinedione, enabling the large-scale synthesis of the active pharmaceutical ingredient with high enantiomeric excess. Through optimization of the entire synthesis method from the perspective of process chemistry, enhancement in yields, complete elimination of chromatographic purification, and reduction in the number of unit operations were achieved. The productivity was dramatically improved compared to the original synthesis route, and the overall yield was increased by approximately 3-fold. This newly developed process consistently provided high-quality and high-yield products in each step, resulting in the efficient and robust synthesis of the PTDSS1 inhibitor on a multikilogram scale.",10.1021/acs.oprd.4c00056,2024-03-26,0.7326293782431986
Organic Process Research & Development,Asymmetric Synthesis of the Cholesteryl Ester Transfer Protein Inhibitor Torcetrapib,"Previously our group reported synthetic efforts used to synthesize kilogram quantities of the cholesteryl ester transfer protein (CETP) inhibitor torcetrapib, 1, via a mid-stage resolution. This account describes research conducted to develop an asymmetric route to this clinical candidate suitable for long-term manufacturing. The first asymmetric center is established via coupling of ( R )-3-aminopentanenitrile to a trifluoromethylarene. After elaboration of the nitrile to a suitable precursor, a key step in the synthesis is diastereoselective cyclization of immonium ion 7 to provide the tetrahydroquinoline core. This approach also permitted a streamlined sequence to complete the synthesis of 1 . Development of the process and synthetic rationale are described.",10.1021/op060013i,2006-03-16,0.7326159503594537
Tetrahedron,"An efficient synthesis of methyl N-[2-(R)-(1-napthylmethyl)-3-(morpholinocarbonyl)propionyl]-(S)-histidinate, the key synthetic intermediate of renin inhibitors",,10.1016/s0040-4039(00)94685-9,1990-01-01,0.7324135360828682
Tetrahedron,A new route to stabilized ylides: A one-pot polyene synthesis,,10.1016/s0040-4039(00)72142-3,1975-01-01,0.7323907163912176
Organic Process Research & Development,"An Improved and Economical Process for the Manufacture of the Key Intermediate of Aliskiren, a New Potent Renin Inhibitor","An improved, practical, economical and efficient process for the production of (2 S,4 S )-2-amino-4-(4-methoxy-3-(3-methoxypropoxy)benzyl)-5-methylhexanoic acid, a key intermediate of the new potent renin inhibitor of aliskiren, in a total yield over 30% is described. This process avoids expensive reagents and chromatographic purifications, and is easily scaled up in industry.",10.1021/op400205k,2013-10-07,0.7320934666964029
Journal of Organic Chemistry,Synthetic Routes to Pyrroloiminoquinone Alkaloids. A Direct Synthesis of Makaluvamine C,"Makaluvamine C is a pyrroloiminoquinone which has been isolated from marine sponges. This molecule has been synthesized in 13 steps from p -anisidine. The key steps in this synthesis include an intramolecular nucleophilic aromatic substitution mediated by potassium tert -butoxide, the selective reduction of a dinitro ester using catalytic hydrogenation, and the novel use of Fremy's salt to synthesize an iminoquinone from an amino phenol. The synthesis of makaluvamine C has been achieved from p -anisidine in 13.1% overall yield.",10.1021/jo981547n,1998-11-26,0.7320090771029076
Organic Process Research & Development,First Generation Process for the Preparation of the DPP-IV Inhibitor Sitagliptin,"A new synthesis of sitagliptin (MK-0431), a DPP-IV inhibitor and potential new treatment for type II diabetes, suitable for the preparation of multi-kilogram quantities is presented. The triazolopyrazine fragment of sitagliptin was prepared in 26% yield over four chemical steps using a synthetic strategy similar to the medicinal chemistry synthesis. Key process developments were made in the first step of this sequence, the addition of hydrazine to chloropyrazine, to ensure its safe operation on a large scale. The beta-amino acid fragment of sitagliptin was prepared by asymmetric reduction of the corresponding beta-ketoester followed by a two-step elaboration to an N -benzyloxy beta-lactam. Hydrolysis of the lactam followed by direct coupling to the triazolopiperazine afforded sitagliptin after cleavage of the N -benzyloxy group and salt formation. The overall yield was 52% over eight steps.",10.1021/op0500786,2005-08-31,0.7318317817129074
Organic Letters,A Concise Synthesis of Butylcycloheptylprodigiosin,A short and efficient total synthesis of the tripyrrole alkaloid butylcycloheptylprodigiosin is described. Key to the brevity of the approach is a two-step synthesis of macrocyclic formylpyrrole 4 from cyclononenone 6.,10.1021/ol070341i,2007-04-18,0.7317026742448626
Organic Process Research & Development,"Process Development and Scale-up Total Synthesis of Largazole, a Potent Class I Histone Deacetylase Inhibitor","Herein we describe the research and development of the process for the scale-up total synthesis of largazole, a potent class I selective histone deacetylase (HDAC) inhibitor, a potential anticancer agent and also useful for the treatment of other disorders where transcriptional reprogramming might be beneficial. The synthetic route and conditions for each fragment and final product were modified and optimized to make them suitable for larger scale synthesis. With the process we developed, hundreds of grams of each fragment and decagrams of final productlargazole were synthesized in good to excellent yields. The final target largazole was obtained in 21% overall yield over eight steps based on the longest sequence with over 95% HPLC purity.",10.1021/acs.oprd.7b00352,2018-01-30,0.7316829329077631
Journal of Organic Chemistry,Practical Synthesis of a Potent Hepatitis C Virus RNA Replication Inhibitor,"A practical, efficient synthesis of 1, a hepatitis C virus RNA replication inhibitor, is described. Starting with the inexpensive diacetone glucose, the 12-step synthesis features a novel stereoselective rearrangement to prepare the key crystalline furanose diol intermediate. This is followed by a highly selective glycosidation to couple the C-2 branched furanose epoxide with deazapurine.",10.1021/jo0491096,2004-08-13,0.7316442323434935
Tetrahedron,An efficient organocatalytic route for asymmetric total synthesis of Stagonolide F,,10.1016/j.tetlet.2015.09.082,2015-09-26,0.7315965353369193
Tetrahedron,"An efficient asymmetric synthesis of a potent COX-2 inhibitor L-784,512",,10.1016/s0040-4039(98)00735-7,1998-06-01,0.731338246256824
Organic Process Research & Development,"Scale-Up Synthesis of a TRPV1 Antagonist Featuring a Facile Thiazolo[5,4-<i>d</i>]pyrimidine Formation","An efficient and practical synthesis of a TRPV1 inhibitor bearing a thiazolo[5,4- d ]pyrimidine core was developed. The initial synthesis was modified to facilitate acylation of 5-aminopyrimidine and subsequent thiazole formation. The synthesis features an efficient two-pot, five-step process for the construction of the thiazolo[5,4- d ]pyrimidine ring. The new route is concise, chromatography-free, and amenable to large-scale preparation.",10.1021/op1002984,2011-01-24,0.731318850967416
Organic Process Research & Development,"Process Development for Scale-Up of a Novel 3,5-Substituted Thiazolidine-2,4-dione Compound as a Potent Inhibitor for Estrogen-Related Receptor 1","The development of a reproducible process for multihundred gram production of ( Z )-5-((1-(4-chloro-2-(trifluoromethyl)benzyl)-1 H -indazol-5-yl)methylene)-3-((3 R,4 R )-3-fluoro-1-methylpiperidin-4-yl)thiazolidine-2,4-dione ( 26 ), a potent and selective inhibitor of estrogen-related receptor 1 (ERR1), is described. This multihundred gram synthesis was achieved via magnesium perchlorate-catalyzed regioselective epoxide ring-opening of tert -butyl 7-oxa-3-azabicyclo[4.1.0]heptane-3-carboxylate ( 9 ) with thiazolidine-2,4-dione ( 6, TZD) to form a diastereomeric mixture tert -butyl 4-(2,4-dioxothiazolidin-3-yl)-3-hydroxypiperidine-1-carboxylate ( 17 ), of which the 3-hydroxyl group was functionally transformed to 3-fluoro derivative 19 after treatment with Deoxo-Fluor. Chiral separation of 19 provided the desired diastereomer (3 R,4 R )- 21 that was converted to the secondary amine 23 TFA salt. Reductive amination of 23 produced the key intermediate N -methyl 24 . Knoevenagel condensation of 24 with 1-(4-chloro-2-(trifluoromethyl)benzyl)-1 H -indazole-5-carbaldehyde ( 5 ) produced the final product 26 in 10% overall yield (99.7% HPLC area% with ≥99.5% de) after a convergent eight synthetic steps with the only column purification being the chiral HPLC separation of 3 R,4 R - 21 from 3 S,4 S - 22 .",10.1021/op400325r,2014-01-18,0.7309508030044903
Organic Process Research & Development,"Development of a Scalable Synthesis of (<i>S</i>)-3-Fluoromethyl-γ-butyrolactone, Building Block for Carmegliptin’s Lactam Moiety",Several new routes are reported for the synthesis of ( S )-3-fluoromethyl-γ-butyrolactone. An asymmetric hydrogenation-based synthesis was chosen as the enabling route to produce the lactone on a 10-kg scale. A superior stereoselective route starting from ( S )- tert -butyl glycidyl ether which afforded the desired lactone in three steps with ∼50% overall yield was finally selected for further development and production.,10.1021/op200019k,2011-04-12,0.730812701292224
Synthesis,"A Concise Synthesis of 6H-Indolo[2,3-b]quinolines: Formal Synthesis of Neocryptolepine","A new two-step approach for the synthesis of 6 H -indolo[2,3- b ]quinolines is described using indole C3 alkylation and a one-pot reduction–cyclization–aromatization sequence. The synthesis of the parent 6 H -indolo[2,3- b ]quinoline system constitutes a formal synthesis of the alkaloid neocryptolepine (cryptotackieine).",10.1055/s-0031-1290812,2012-04-05,0.7305755325948916
Organic Process Research & Development,The Development of a Robust Process for a CRF<sub>1</sub> Receptor Antagonist,"A scalable and robust process was developed for the preparation of pexacerfont ( 2 ), a pyrazolotriazine corticotropin-releasing factor receptor 1 antagonist (CRF 1 ). The formation of the core hydroxypyrazolotriazine moiety was achieved through two consecutive cyclizations of a semicarbazide, employing reaction conditions that are significantly milder than those reported in the literature. Further conversion to the key chloropyrazolotriazine intermediate was accomplished through a novel catalytic process using phosphorous oxychloride as the chlorinating agent. The active pharmaceutical ingredient 2 was obtained in >99.5% purity with a 68% overall yield for the six synthetic steps.",10.1021/op100270u,2011-01-31,0.7305396579076532
Journal of Organic Chemistry,A Synthetic Route to (±)-Clavizepine through a Dibenzoxepine Intermediate,"A new synthesis of (±)-clavizepine ( 1a ), based on the dibenzoxepinediol 10 as main intermediate is described. The key step is the contraction of the oxepine ring to give the xanthene-9-carboxyaldehyde 11, on which the nitrogenated ring can be readily assembled.",10.1021/jo960291n,1996-01-01,0.7305124530986807
Journal of Organic Chemistry,An approach to the BCDE ring of quasimarin,"A 10-step route to the BCDE ring system of quasimarin (1) is described. Key features of the route include the regioselective protection of diketone 7 by use of intramolecular ketal formation, a two-step lactone to ether reduction, and a regioselective lactonization. The tetracyclic system 15 is produced in 29% overall yield.",10.1021/jo00143a020,1982-10-01,0.7304676301719616
Organic Process Research & Development,A Practical Synthesis of 7-Azaindolylcarboxy-<i>e</i><i>ndo</i>-tropanamide (DF 1012),"An optimised cost-effective synthesis of the new antitussive drug, DF1012, is herewith reported. The new synthetic route to the key intermediate DF1005 is based on the unusual deprotection step of the 1- tert -butyl-3-cyano-7-azaindole intermediate, which can also be regarded as a convenient way for the industrial production of the expensive 7-azaindole 1 . The second key intermediate, endo -tropanamine 6, was obtained in high yield by a novel one-pot stereoselective process using a Pd-catalysed reductive amination procedure.",10.1021/op025570t,2003-02-21,0.7303813986989564
Organic Process Research & Development,Development of a Cost-Efficient Process Toward a Key Synthetic Intermediate of the EZH2 Inhibitor PF-06821497,A cost-efficient approach for the synthesis of a key intermediate of the EZH2 inhibitor PF-06821497 was identified after performing process chemistry development. A wide route scouting effort was initially deployed to finally identify a successful oxidative decyanation approach. Widely available raw materials were utilized to access a desired oxetanyl-ketone as a precursor for a KRED process to generate the enantioenriched alcohol in 99% ee. Subsequent methylation followed by a carboxylation led to our targeted building block in seven steps with an overall yield of 28%. This process was demonstrated on a large scale to produce up to 50 kg of our key intermediate in the synthesis of PF-06821497.,10.1021/acs.oprd.3c00477,2024-02-26,0.7303642452230984
Organic Process Research & Development,Multikilogram Synthesis of a Potent Dual Bcl-2/Bcl-x<sub>L</sub> Antagonist. 1. Manufacture of the Acid Moiety and Development of Some Key Reactions,"Our efforts toward the process development of drug candidate 1 are described in a series of two papers. This manuscript focuses on the synthesis of kilogram quantities of acid precursor 2 to provide batches of material for preclinical studies and first-in-human clinical trials. Our approach relies on a chiral resolution to furnish the desired stereocenter, a cryogenic carboxylation, and N -alkylation of chloride derivative 26 prepared by a Suzuki coupling. Further efforts pursued to improve those key steps that could become issues on larger scale are also discussed.",10.1021/acs.oprd.9b00364,2019-11-19,0.7303257914062329
Organic Process Research & Development,"The Synthesis of (<i>S</i>)-5-Fluoro-1-(2-fluorophenyl)-3-(piperidin-3-ylmethoxy)-1<i>H</i>-indazole, a Norepinephrine/Serotonin Reuptake Inhibitor for the Treatment of Fibromyalgia","Compound 1, a norepinephrine/serotonin reuptake inhibitor (NSRI) for the treatment of fibromyalgia, has been synthesized in optically pure form in six linear steps and 48% overall yield with no chromatography. This route features a novel and efficient intramolecular cyclization to generate the indazolone core via a diazotization reaction and the preparation of a stable polymorph of the tartaric acid salt as the desired final form. The original synthetic route has been modified to avoid the use of toxic and expensive reagents, thus enabling the preparation of multigram quantities of API for toxicology studies.",10.1021/op800113s,2008-08-09,0.730186428383992
Journal of Organic Chemistry,Synthesis of the Selective D<sub>2</sub> Receptor Agonist PNU-95666E from <scp>d</scp>-Phenylalanine Using a Sequential Oxidative Cyclization Strategy,"Compound 1 (PNU-95666E) is a selective and high-affinity agonist at the dopamine D 2 receptor subtype and is of interest as a potential agent for the treatment of Parkinson's disease. Requiring a synthetic route amenable to scale-up, a synthesis of this enantiomerically pure tricyclic compound was developed, starting from d -phenylalanine. Critical to the success of this synthesis were two oxidative nitrogen annulations to provide the tricyclic ring system. A highly efficient reduction with borane−methyl sulfide was used to reduce three different functional groups, a total of six hydrides transferred, with no concomitant racemization, contributing to the synthesis of 1 in eight steps with an overall yield of 26%. The utility of this synthetic route has been demonstrated by the completion this synthesis on multikilogram scale.",10.1021/jo970526a,1997-09-01,0.7301739346411046
Synthesis,Stereocontrolled Synthesis of (±)-Grandisol,"Abstract A synthetic approach to grandisol is described. The route to the cyclobutane core relies on an efficient intramolecular [2+2] cyclo­addition that establishes the required cis-ring fusion at the adjacent side chains of the cyclobutane ring. Using a new two-step lithium/halide homologation procedure, norgrandisol was efficiently converted into grandisol. This new approach enables the synthesis of grandisol in five steps from commercially available starting material in 22% overall yield.",10.1055/s-0040-1719910,2022-04-06,0.7301220044126454
Organic Process Research & Development,"Development of a Bulk Enabling Route to Maraviroc (UK-427,857), a CCR-5 Receptor Antagonist","A bulk enabling synthesis of the CCR-5 receptor antagonist, Maraviroc (UK-427,857) ( 1 ), is presented. Synthesis of the three key fragments, β-amino ester 3, 4,4-difluorohexanecarboxylic acid ( 2 ), and 1,3,4-triazole-substituted tropane fragment 4 are described. Coupling strategies for these fragments are discussed and described, including synthetic challenges, protection strategies, impurity generation, and final scale-up of the developed route to 1 .",10.1021/op8000614,2008-10-04,0.7300329485709992
Organic Letters,Enantioselective Formal Synthesis of (+)-Cycloclavine and Total Synthesis of (+)-5-<i>epi</i>-Cycloclavine,"Starting from the commercially available 4-bromoindole, a concise and efficient enantioselective formal synthesis of (+)-cycloclavine ( 1 ) in 13 steps with 2.0% overall yield and a total synthesis of (+)-5- epi -cycloclavine ( 2 ) in 14 steps with 3.3% overall yield were achieved. Key features of the syntheses include the addition of a Grignard reagent to the C═N/Heck reaction sequence to construct the fused 6–5–6 ring systems, cyclopropanation, an ester aminolysis reaction, and the first example of the construction of a 3-azabicyclo[3,1,0]hexane through an intramolecular [3 + 2] cycloaddition/nitrogen extrusion.",10.1021/acs.orglett.9b02015,2019-08-14,0.7299543631345635
Organic Process Research & Development,The Development of an Effective Synthetic Route of Belinostat,"A practical synthetic route of belinostat is reported. Belinostat was obtained via a five-step process starting from benzaldehyde and including addition reaction with sodium bisulfite, sulfochlorination with chlorosulfonic acid, sulfonamidation with aniline, Knoevenagel condensation, and the final amidation with hydroxylamine. Key to the strategy is the preparation of 3-formylbenzenesulfonyl chloride using an economical and practical protocol. The main advantages of the route include inexpensive starting materials and acceptable overall yield. The scale-up experiment was carried out to provide 169 g of belinostat with 99.6% purity in 33% total yield.",10.1021/acs.oprd.6b00170,2016-07-12,0.7299510734969402
Journal of Organic Chemistry,First Total Synthesis of Louisianin A,"The first total synthesis of louisianin A, 4-allyl-6,7-dihydro-1-hydroxycyclopenta[c]pyridin-5-one, is achieved from 2-chloro-4-cyanopyridine 5 via seven steps in an overall 24% yield. The key step is a cyclization-decarboxylation sequence toward the formation of a cyclopentenone ring.",10.1021/jo060935j,2006-07-07,0.7299176803919063
Journal of the American Chemical Society,Efficient Synthesis of Okadaic Acid. 2. Synthesis of the C1−C14 Domain and Completion of the Total Synthesis,"Described here are the full details of the preparation of a synthetic intermediate representing carbons 1−14 (C1−C14) of the marine natural product okadaic acid ( 1 ), the coupling of this fragment with the previously prepared C15−C38 domain, and the completion of an efficient total synthesis of 1 . The C1−C14 intermediate was prepared in 11 steps and ∼20% overall yield from a functionalized δ-valerolactone derivative representing C3−C8 of 1 . This featured a classic spiroketalization strategy to construct the highly substituted 1,7-dioxaspiro[5.5]undec-4-ene system, followed by incorporation of the intact C1−C2 α-hydroxyl, α-methyl carboxylate moiety using cis- ( S )-lactate pivalidene enolate. The complete C1−C14 intermediate was converted into 1 in five additional steps. Coupling of the C1−C14 fragment with the C15−C38 domain of 1 via C14 aldehyde and C15 β-keto phosphonate moieties provided the complete carbon skeleton of 1 bearing a ketone at C16 and a mixed-methyl acetal at C19. Reduction of the C16 ketone using Corey's ( S )-CBS/BH 3 system and subsequent acid-triggered spiroketalization formed the central 1,6-dioxaspiro[4.5]decane ring system. Saponification of the C1−C2 pivalidene group and final reductive cleavage of the three benzyl ethers using lithium di- tert -butylbiphenylide in THF provided 1 in 48% yield from the C1−C14 aldehyde, and in 26 steps and ∼2% overall yield in the longest linear sequence from the C22−C27 synthon methyl 3- O -benzyl-α- d -altropyranoside.",10.1021/ja973286p,1998-03-01,0.7298553512366458
Tetrahedron,Practical and efficient total synthetic route of the resveratrol dimer (±)-ε-viniferin,,10.1016/j.tetlet.2022.153775,2022-03-31,0.7298450530349935
Organic Process Research & Development,Development of a Continuous Process for the Large-Scale Asymmetric Manufacture of (<i>R</i>)-3-Methoxy-2-(4-methylpiperazin-1-yl)propanoic Acid,"A large-scale enantioselective manufacturing route to an unusual piperazine-substituted amino acid is described. Previous synthetic routes to this amino acid relied on the resolution of racemic mixtures using l -tartaric acid that was demonstrated on a 6 kg scale, but this resulted in a reduced overall yield and efficiency. The new enantioselective route to this amino acid uses the S N 2 displacement of a chiral triflate with N -methylpiperazine that proceeds with very high levels of stereocontrol. The key chiral triflate is prepared in five synthetic steps in 38% overall yield and >99% enantiomeric purity (e.p.), starting from cheap and readily available d -serine. Subsequent reaction with N -methylpiperazine was initially demonstrated in batch, providing the benzyl-protected amino acid in 83% e.p. on a 3 kg scale. This transformation was further improved by the application of continuous manufacture to provide the benzyl-protected ester in >99% e.p. on an 80 kg scale. Simple deprotection of the benzyl ester group by hydrogenolysis, followed by isolation of the amino acid as the corresponding dihydrochloride salt, provided a scalable and efficient synthesis of ( R )-3-methoxy-2-(4-methylpiperazin-1-yl)propanoic acid in good overall yield (33%) and very high optical purity (>99.5% e.p.).",10.1021/acs.oprd.3c00409,2024-04-08,0.7298442213446322
Journal of Organic Chemistry,Coupling-Condensation Strategy for the Convergent Synthesis of an Imidazole-Fused 2-Aminoquinoline NLRP3 Agonist,"The development of a convergent route to the NLRP3 (nucleotide-binding domain and leucine-rich repeat-containing protein 3) agonist BMS-986299 is reported. The synthesis relies on a key Miyaura borylation and a tandem Suzuki–Miyaura coupling between an iodoimidazole and an o -aminochloroarene, followed by acid-mediated cyclization to afford the aminoquinoline core. The subsequent Boc cleavage and regioselective acylation afford the target compound. Two routes to the iodoimidazole intermediate are presented, along with the synthesis of the o -aminochloroarene via Negishi coupling. The convergent six-step route leads to an 80% reduction in process mass intensity compared to the linear enabling synthesis.",10.1021/acs.joc.2c02395,2022-12-14,0.7297894994808929
Organic Process Research & Development,"Efficient Asymmetric Synthesis of <i>N</i>-[(1<i>R</i>)-6-Chloro-2,3,4,9-tetrahydro-1<i>H</i>-carbazol-1-yl]-2-pyridinecarboxamide for Treatment of Human Papillomavirus Infections","An efficient asymmetric synthesis of N -[(1 R )-6-chloro-2,3,4,9-tetrahydro-1 H -carbazol-1-yl]-2-pyridinecarboxamide 1, a potential treatment for human papillomavirus infections, is described. The key step in the synthesis of this molecule is an asymmetric reductive amination directed by chiral (phenyl)ethylamines resulting in up to 96% disastereo facial selectivity. The synthesis is also highlighted by isolation of a unique 2-picolinic acid salt of (1 R )-6-chloro-2,3,4,9-tetrahydro-1 H -carbazol-1-amine ( 13 ). Subsequent application of 1-propylphosphonic acid cyclic anhydride (T3P) for convenient amide formation from the two components of the salt provides the product 1 in high yield. The process research work leading to the final synthesis includes a racemic synthesis followed by resolution with chiral supercritical fluid chromatography, and an enantioselective reductive amination via chiral transfer hydrogenation catalyzed by Ru(II) complexes of N -[(1 S,2 S )-2-amino-1,2-diphenylethyl]-1-naphthalenesulfonamide or ( R )-BINAP. Highlighting the practicality of the synthesis, the process has been scaled up in 200-gallon reactors for delivery of multikilograms of the target compound 1 in over 99.5% enantiomeric purity.",10.1021/op060223v,2007-02-14,0.7297865265616936
Organic Letters,"Judicious Application of Allyl Protecting Groups for the Synthesis of 2-Morpholin-4-yl-4-oxo-4<i>H</i>-chromen-8-yl Triflate, a Key Precursor of DNA-Dependent Protein Kinase Inhibitors","[Structure: see text] 2-morpholin-4-yl-4-oxo-4H-chromen-8-yl 2,2,2-trifluoromethanesulfonate is a key intermediate for the synthesis of the DNA-dependent protein kinase (DNA-PK) inhibitor 8-dibenzothiophen-4-yl-2-morpholin-4-yl-chromen-4-one (NU7441). Two improved methods for the synthesis of this triflate have been developed: (A) in 35% overall yield, through modification of the published route, and (B) in 15% overall yield, by a new route employing a Baker-Venkataraman rearrangement to enable generation of the chromenone scaffold. Both syntheses depend on the judicious use of allyl protecting groups.",10.1021/ol062297x,2006-11-18,0.7296847342166456
European Journal of Organic Chemistry,Novel Approach for the Synthesis of Five‐Membered‐Ring‐Fused Pyrazinones,Abstract We describe a new route to access important pharmaceutical intermediates for the synthesis of constrained fused pyrazinones. These compounds are prepared in five to seven steps with a good overall yield from glycine methyl ester and commercial propanediol derivatives involving an intramolecular alkylation of a glycine moiety as key step.,10.1002/ejoc.201000435,2010-05-20,0.7296633405238344
Organic Letters,Total Synthesis of (+)-Aureol,"A total synthesis of the marine sponge meroterpenoid (+)-aureol has been achieved in 12 steps (6% overall yield) from (+)-sclareolide. Key steps of the synthesis include a biosynthetically inspired sequence of 1,2-hydride and methyl shifts, and a biomimetic cycloetherification reaction.",10.1021/ol301715u,2012-09-04,0.7296335330299709
Organic Process Research & Development,Synthesis of Akt Inhibitor Ipatasertib. Part 2. Total Synthesis and First Kilogram Scale-up,"Herein, the first-generation process to manufacture Akt inhibitor Ipatasertib through a late-stage convergent coupling of two challenging chiral components on multikilogram scale is described. The first of the two key components is a trans -substituted cyclopentylpyrimidine compound that contains both a methyl stereocenter, which is ultimately derived from the enzymatic resolution of a simple triester starting material, and an adjacent hydroxyl group, which is installed through an asymmetric reduction of the corresponding cyclopentylpyrimidine ketone substrate. A carbonylative esterification and subsequent Dieckmann cyclization sequence was developed to forge the cyclopentane ring in the target. The second key chiral component, a β 2 -amino acid, is produced using an asymmetric aminomethylation (Mannich) reaction. The two chiral intermediates are then coupled in a three-stage endgame process to complete the assembly of Ipatasertib, which is isolated as a stable mono-HCl salt.",10.1021/op500270z,2014-11-02,0.7295156026326741
Organic Process Research & Development,Development of an Efficient and Scalable Biocatalytic Route to (3<i>R</i>)-3-Aminoazepane: A Pharmaceutically Important Intermediate,"An efficient and novel route to (3 R )-3-aminoazepane ( 1 ) is described. The target is obtained with 99.92% purity, 99.2% ee in seven steps, and 46.2% overall yield. This improved method involves a practical biocatalytic transformation with ω-transaminase to establish the stereogenic center high efficiently as a key step. The developed process was scalable, cost-effective, with a simplified reaction workup, avoiding the use of expensive metal catalyst or chromatography, and commercially viable for the synthesis of 1 .",10.1021/acs.oprd.7b00074,2017-03-29,0.7294428003624933
Organic Process Research & Development,"Development of a Second-Generation, Highly Efficient Manufacturing Route for the HIV Integrase Inhibitor Raltegravir Potassium","A manufacturing route for the synthesis of raltegravir potassium 1 was developed via a thermal rearrangement of amidoxime DMAD adducts 6 to construct the key, highly functionalized hydroxypyrimidinone core 7 . Utilizing this route 1 was prepared in nine linear chemical steps with 22% overall yield. A second-generation synthesis was subsequently developed that solved the key chemical, productivity, and environmental impact issues of the initial synthesis. Highlights of the new synthesis include a highly selective methylation, 3−4-fold higher productivity, and a 65% reduction of combined organic and aqueous waste produced. The efficient second-generation manufacturing route provides raltegravir potassium 1 in 35% overall yield.",10.1021/op100257r,2010-11-16,0.7292353970059599
Tetrahedron,A new synthetic route to (±)-lysergie acid,,10.1016/0040-4039(76)80103-7,1976-11-01,0.7291355814504297
Synlett,Synthesis of a Novel Serotonin-3 (5-HT<sub>3</sub>) Receptor Antagonist,"All articles of this category A practical method for the synthesis of ONO-3051 {6-amino-7-chloro-2-[(5-methyl-4-imidazolyl)methyl]isoquinolin-1-(2 H )-one ( 3 )}, a highly potent and orally active serotonin-3 (5-HT 3 ) receptor antagonist, was developed. This method includes an efficient synthesis of a key intermediate, 6-amino-7-chloroisoquinolin-1(2 H )-one ( 10 ).",10.1055/s-1992-21405,1992-01-01,0.7290767547039896
Organic Letters,"Total Synthesis of (±)-Agelastatin A, A Potent Inhibitor of Osteopontin-Mediated Neoplastic Transformations","A stereoselective synthesis of agelastatin A, a potent cytotoxin and inhibitor of osteopontin (OPN)-mediated neoplastic transformations, has been accomplished in 14 steps (12 operations) with an approximate overall yield of 8%. Notable features of this route include the direct manner in which the pyrroloketopiperazine A-ring of the target is generated and the efficient employment of a trichloroacetamide, introduced through Overman rearrangement, as a protecting group, pendant nucleophile, and latent urea.",10.1021/ol900133v,2009-02-19,0.7289416659301513
Organic Process Research & Development,Chemistry Development of a Convergent Route to Trecetilide Hemi-Fumarate,"A novel, efficient, stereoselective synthetic route for N -(4-{4-[ethyl(6-fluoro-6-methylheptyl)amino]-1-( S )-hydroxybutyl}phenyl)methanesulfonamide hemi-fumaric acid salt (trecetilide hemi-fumarate, Figure 1) has been developed. The process features a convergent approach, which assembles two key intermediates in the last step to form the final molecule, which is then isolated by pH-controlled extraction. The new route offers significant yield and purity advantages over the previous route. However, the solvent volume and cycle time were not fully optimized due to the termination of the project.",10.1021/op049799f,2005-03-01,0.7288470744692253
Organic Process Research & Development,Development of an Early Enabling Synthesis for PF-03052334-02: A Novel Hepatoselective HMG-CoA Reductase Inhibitor,"Early process development work toward a promising pyrazole-based HMG-CoA reductase inhibitor is described. PF-03052334-02 ( 1 ) was prepared in 14 synthetic steps with a 21% overall yield, highlighted by a modified three-step hydroxypyrazole formation in which the yield was improved from 37% to 73%, a Suzuki/ozonolysis pathway that streamlined the downstream chemistry, and a reversed Wittig olefination strategy that improved the key coupling step from 50% to 95% yield. Multiple process hazards and most chromatography steps were removed, and a highly effective active pharmaceutical ingredient (API) salt formation, purification, and isolation protocol was also developed.",10.1021/op100268e,2010-12-17,0.7286898393057345
Organic Process Research & Development,Progress in the Synthesis of OPC-15161:  Easy Access to Dioxygenated Pyrazine <i>N</i>-Oxide Structure,"An improved synthetic route to OPC-15161 ( 1 ), a novel inhibitor of superoxide anion generation, is described. Choice of the protecting group is the key to the second-generation synthesis. Usefulness of the 2-cyanoethyl (CE)-protecting group in our process research is emphasized in comparison with that of other protecting groups. This process can be carried out in four steps with 40% overall yield from tryptophan methyl ester, which also opens a general route for the preparation of the related 5-alkoxypyrazin-2(1 H )-one 4-oxides.",10.1021/op000029n,2000-08-05,0.7286892607812141
Organic Letters,Total Synthesis of (+)-Cyperolone,"The total synthesis of (+)-cyperolone, an eudesmane-derived sesquiterpenoid from Cyperus rotundus, is described. The de novo synthesis was accomplished via a 15 step sequence starting from (R)-(-)-carvone. The synthetic route features a platinum-catalyzed cycloisomerization to rapidly construct the bicyclic core from a 3-silyloxy-1,5-enyne intermediate.",10.1021/ol300058t,2012-02-10,0.728475590539623
Organic Letters,Synthesis of Taurospongin A,"Two new routes to the C(1-10) carboxylic acid core of taurospongin A are presented. In the first route, overall asymmetric hydration of a C(2)-C(3) alkene is achieved by Sharpless AD and selective deoxygenation at C(2); in the second route, the C(3) stereogenic center is set by Tietze asymmetric allylation. A short synthesis of the C(1'-25') fatty acid combines with the product from the first route to complete the total synthesis of taurospongin A.",10.1021/ol100906k,2010-05-18,0.7284549456905216
Organic Process Research & Development,"Novel Approaches towards the LTD<sub>4</sub>/E<sub>4</sub> Antagonist, LY290154","Several novel approaches have been investigated for the synthesis of the LTD 4 /E 4 antagonist LY290154. Significant improvements to the discovery route were first made by using an indoline nucleophile instead of an indolyl anion in the key substitution step. An alternative approach, introducing the 7-chloroquinoline moiety in the latest stages of the synthesis was then demonstrated. Interestingly, the pivotal intermediate of this latter route was also obtained in a one-pot process following a Katritzky methodology. Finally, an asymmetric synthesis offering significant advantages over the enantioselective route reported by McKillop was demonstrated.",10.1021/op060036x,2006-05-13,0.7284509664584388
Organic Process Research & Development,An Improved Synthesis of a Selective Serotonin Reuptake Inhibitor,"A practical synthesis of 3-((1 S, 2 S )-2-dimethylaminomethylcyclopropyl)-1 H -indole-5-carbonitrile hydrochloride ( 1 ), a selective serotonin reuptake inhibitor (SSRI), is described. The process to prepare 1 was demonstrated on laboratory scale and highlights an enantioselective Simmons−Smith cyclopropanation of allylic alcohol 3 using Charette’s chiral dioxaborolane ligand. The improved synthesis enabled production of 1 in 8 chemical steps (5 isolations) in an overall yield of 38%.",10.1021/op700126w,2008-01-17,0.7283760518598393
Organic Process Research & Development,"A Practical Synthesis of Enantiopure 7-Alkoxy-4-aryl-tetrahydroisoquinoline, a Dual Serotonin Reuptake Inhibitor/Histamine H<sub>3</sub> Antagonist","An efficient synthesis of compound 1 featuring a novel sequential Friedel–Crafts alkylation strategy to construct the 4-aryl-tetrahydroisoquinoline core structure has been developed. Resolution with ( d / l )-di- p -toluoyl-tartaric acid is utilized to provide the enantiomerically pure material. Overall, the route is concise and amenable for large-scale synthesis.",10.1021/op700183q,2007-11-01,0.7283501802394701
Tetrahedron,Enantioselective route to an AE-ring intermediate in the total synthesis of talatisamine,,10.1016/j.tetlet.2023.154903,2023-12-28,0.728276121887211
Organic Process Research & Development,Application of the Tisler Triazolopyrimidine Cyclization to the Synthesis of a Crop Protection Agent and an Intermediate,"A new synthetic route to the Dow AgroSciences early stage sulfonamide herbicide 3-(2-methoxy-4-trifluoromethyl)- N -(5,7-dimethoxy[1,2,4]triazolo[1,5- a ]pyrimidin-2-yl)pyridinesulfonamide (pyroxsulam) has been developed. The synthesis is based on formation of the triazole ring as the final step, utilizing the Tisler triazolopyrimidine cyclization. A Tisler cyclization route to 2-amino-5,7-dimethoxy-1,2,4-trazolo[1,5- a ]pyrimidine starting with 2-chloro-4,6-dimethoxypyrimidine has also been demonstrated.",10.1021/op0601518,2006-10-24,0.7282534758587023
Organic Process Research & Development,Manufacture of the PI3K β-Sparing Inhibitor Taselisib. Part 2: Development of a Highly Efficient and Regioselective Late-Stage Process,"A highly efficient and regioselective manufacturing route for the phosphoinositide 3-kinase β-sparing inhibitor taselisib was developed. Highlights of the synthesis include: (1) magnesium-mediated formation of a challenging cyclic amidine; (2) regioselective imidazole construction via alkylation/condensation with bromopyruvic acid; and (3) triazole formation with 2-isopropyl acetamidrazone to generate the key bromobenzoxazepine core intermediate. Subsequent highly efficient one-pot palladium-catalyzed Miyaura borylation/Suzuki cross-coupling/saponification, followed by a 1,1′-carbonyldiimidazole-mediated coupling with ammonia, led to the pentacyclic taselisib. This new synthetic approach provides a more efficient route to taselisib with a significant decrease in process mass intensity compared to the previous early development routes to the bromobenzoxazepine core. Finally, implementation of a controlled crystallization provided the active pharmaceutical ingredient with the desired polymorphic form.",10.1021/acs.oprd.9b00050,2019-03-06,0.7282143638238677
Organic Process Research & Development,Development of a Scalable Synthesis of a Bruton’s Tyrosine Kinase Inhibitor via C–N and C–C Bond Couplings as an End Game Strategy,"A scalable and convergent synthesis of a BTK (Bruton’s tyrosine kinase) inhibitor has been developed. Synthetic routes to key intermediates were explored for the scale-up campaign, especially the process for 6-dimethylaminodihydroisoquinolinone, which was prepared via a regioselective cyclization of an isocyanate, mediated by AlCl 3 . Improved routes to key building blocks were demonstrated by expedient multikilogram productions. The target compound was assembled through a Pd-catalyzed amidation reaction followed by a Suzuki–Miyaura cross-coupling reaction.",10.1021/op4001077,2013-08-27,0.7281704688395312
Organic Process Research & Development,Development of a Scalable Route to a Dual NK-1/Serotonin Receptor Antagonist,"The evolution of a process for the preparation of a new heterocyclic dual NK1/serotonin receptor antagonist is described. The final synthesis features a telescoped sequence in which an iron(III)-catalyzed Grignard coupling is followed by a benzylic chlorination utilizing trichlorocyanuric acid to construct an unsymmetrical 2,4,6-trisubstituted pyridine. Etherification of a 4,4′-arylhydroxymethane substituted piperidine fragment completes the synthesis of the active pharmaceutical ingredient in 44% overall yield.",10.1021/op300323k,2013-01-10,0.7279190873297612
Tetrahedron,Total synthesis of (±)-desoxycodeine-d: a novel route to the morphine skeleton,,10.1016/s0040-4039(99)02188-7,2000-02-01,0.7278951859378185
Journal of Organic Chemistry,Concise Synthesis of Telmisartan via Decarboxylative Cross-Coupling,"An efficient synthesis of the angiotensin II receptor antagonist telmisartan is presented involving a decarboxylative cross-coupling of isopropyl phthalate (1) with 2-(4-chlorophenyl)-1,3-dioxolane (2c) as the key step (85% yield). The benzimidazole moiety is constructed regioselectively via a reductive amination-condensation sequence, replacing the previously published route via alkylation of the preformed benzimidazole. The product is obtained in an overall yield of 35% in a convergent synthesis with the longest sequence consisting of eight steps.",10.1021/jo801937h,2008-10-22,0.727828181725166
Journal of Organic Chemistry,Enantioselective Total Synthesis of (−)-(<i>S</i>)-Stepholidine,"Enantioselective total synthesis of (-)-(S)-stepholidine, a drug candidate for the treatment of schizophrenia and/or drug abuse, is described. Asymmetric transfer hydrogenation of imines with use of Noyori's catalyst was used as the key step and (-)-(S)-stepholidine was synthesized in 6 steps, with 42% overall yield and >99% ee.",10.1021/jo9020826,2009-10-30,0.7278152200070738
Synlett,A New Enantioselective Route to Bisabolane Sesquiterpenes Phenols: Synthesis of (<i>S</i>)-(+)-Curcuphenol and (<i>S</i>)-(+)-Curcumene,,10.1055/s-1998-1905,1998-11-01,0.7277509175674413
Organic Process Research & Development,Practical and Efficient Approach to Scalable Synthesis of Rucaparib,"A scalable synthesis of rucaparib was developed from methyl 5-fluoro-2-methyl-3-nitrobenzoate and 4-cyanobenzaldehyde. Methyl 5-fluoro-2-methyl-3-nitrobenzoate was converted into a 2-aminocinnamonitrile derivative, which was subjected to the imino-Stetter reaction with 4-cyanobenzaldehyde to yield trisubstituted indole-3-acetonitrile. The reduction of both nitriles, followed by azepinone scaffold construction and selective monomethylation, completed the synthesis of rucaparib. This synthetic route features the use of inexpensive starting materials, scalability, and ease of purification through recrystallization.",10.1021/acs.oprd.4c00366,2024-11-15,0.7277109108762243
Tetrahedron,A new synthetic route to (−)-cassine via asymmetric aminohydroxylation,,10.1016/j.tetlet.2007.05.005,2007-05-09,0.7277085793519112
Journal of Organic Chemistry,"A Practical Enantioselective Synthesis of Odanacatib, a Potent Cathepsin K Inhibitor, via Triflate Displacement of an α-Trifluoromethylbenzyl Triflate",An enantioselective synthesis of the Cathepsin K inhibitor odanacatib (MK-0822) 1 is described. The key step involves the novel stereospecific S(N)2 triflate displacement of a chiral alpha-trifluoromethylbenzyl triflate 9a with (S)-gamma-fluoroleucine ethyl ester 3 to generate the required alpha-trifluoromethylbenzyl amino stereocenter. The triflate displacement is achieved in high yield (95%) and minimal loss of stereochemistry. The overall synthesis of 1 is completed in 6 steps in 61% overall yield.,10.1021/jo8020314,2009-01-13,0.7274411110746574
Organic Process Research & Development,Synthesis of the NK1 Receptor Antagonist GW597599. Part 2: Development of a Scalable Route to a Key Chirally Pure Arylpiperazine,"GW597599 1 is a novel NK-1 antagonist currently under investigation for the treatment of CNS disorders and emesis. The initial chemical development synthetic route, derived from the one used by medicinal chemistry, involved several hazardous reagents, gave low yields, and produced high levels of wastes. Through a targeted process of research and development, application of novel techniques, and extensive route scouting, a synthetic route for GW597599 has been developed. This paper reports the optimisation work of the second stage in the chemical synthesis of GW597599: the development of a pilot-plant-suitable process for the manufacturing of an optically pure arylpiperazine derivative. In particular, the new process eliminates the need to purchase and store dangerous and expensive borane by generating it in situ and also the need for a chlorinated solvent, thereby improving the safety of the process and substantially reducing the overall waste. The final yield and throughput will be significantly enhanced.",10.1021/op8002823,2009-02-24,0.7273794767597425
Organic Process Research & Development,Scalable Ruthenium-Catalyzed Asymmetric Synthesis of a Key Intermediate for the β2-Adrenergic Receptor Agonist,"An enantioselective and robust synthetic process to obtain a useful intermediate for the β2-adrenergic receptor agonist is described. Asymmetric transfer hydrogenation of ketone 1c by ( S, S )- 3b (Ms-DENEB) afforded chiral alcohol 2c in 71% isolated yield and 99% ee. The deprotection completed the synthesis of ( R )- 5 in 41% overall yield from 1b, which is readily commercially available.",10.1021/op500338d,2014-12-10,0.7273698443456409
Organic Process Research & Development,Optimized Synthetic Route for Enantioselective Preparation of (<i>S</i>)-Metolachlor from Commercially Available (<i>R</i>)-Propylene Oxide,"An enantioselective preparation of ( S )-metolachlor has been accomplished. The synthetic route featured the asymmetric preparation of chiral intermediates and the final ( S )-metolachlor from commercially available ( R )-propylene oxide and a key Fukuyama’s process. The key steps, control points, separation purifications, and the whole process are optimized, and the target compound has been successfully prepared in five steps in 51–55% overall yield with excellent enantioselectivity (99% ee) up to a 30 g scale. By judicious choice of synthetic route and selection of starting materials and intermediates, no column chromatographic methods are needed for the separation and purification of the intermediates and the final products. The same strategy was extended as a general method for a series of pesticides and herbicide analogs of Metalaxyl-M and Dimethenamid-P.",10.1021/acs.oprd.7b00216,2017-09-06,0.727297034507193
Organic Process Research & Development,Development of a Practical Synthesis of a Purine Nucleoside Phosphorylase Inhibitor: BCX-4208,"A practical synthesis of the purine nucleoside phosphorylase (PNP) inhibitor BCX-4208 ( 1) was accomplished in three telescoped steps. Mannich condensation of the 4-benzyloxy-9-deazahypoxanthine with (3 R,4 R )-3-hydroxy-4-(hydroxymethyl)pyrrolidine and formaldehyde followed by removal of the protecting group and crystallization furnished the desired product as a hydrochloride salt in 85% overall yield and 99.8% purity. A scalable synthesis of 9-deazahypoxanthine is also reported.",10.1021/op9001142,2009-07-24,0.7272001157406531
Journal of Organic Chemistry,An Improved Route to PUGNAc and Its <i>Galacto</i>-Configured Congener,"An efficient, scalable, and reliable synthesis of PUGNAc and its galacto-configured congener is reported.",10.1021/jo100614b,2010-05-05,0.7270359728585921
Organic Process Research & Development,A Practical Synthesis of an Aminopyridine as a Component of a BTK Inhibitor,"Development of a new route to the BTK intermediate, 5-(1-(azetidin-1-yl)-2-methylpropan-2-yloxy)pyridin-2-amine ( 7 ), has resulted in significant improvements in terms of yield, purity, and operability over the previously known synthesis. The new route was demonstrated on a multihundred-gram scale, and the overall yield of 7 from 2-chloro-5-hydroxypyridine ( 1 ) was improved to 72%. Lithium aluminum hydride, a Swern oxidation, cesium carbonate, azetidine free base, and four chromatographic purifications used in the earlier synthesis were eliminated.",10.1021/op400046y,2013-04-22,0.7268097821989302
Journal of Organic Chemistry,A Short and Efficient Synthesis of Crocetin-dimethylester and Crocetindial,"In this paper we describe an efficient six-step synthesis of crocetin-dimethylester that could be further reduced to a ""four-step"" synthesis through the use of in situ procedures. The simplicity of the whole process, the ready availability of starting materials, and the high overall yield render this strategy a very attractive synthesis of this very important compound, which is the key intermediate for the synthesis of several carotenoids and other polyene natural products.",10.1021/jo034545y,2003-10-23,0.7268068887887348
Organic Letters,Formal Total Synthesis of Neopeltolide,"A concise synthesis of the core structure of the macrolide neopeltolide was developed featuring a Prins cyclization to fashion the pyran ring. Key steps in the synthesis of aldehyde 16 were a Leighton allylation and a Feringa-Minnaard asymmetric methyl cuprate addition to an unsaturated thioester. For lactonization, a classical Yamaguchi macrolactonization was used. The longest linear sequence consists of 17 steps providing lactone 26 with an overall yield of 23%.",10.1021/ol8001255,2008-02-27,0.726742170265346
Organic Process Research & Development,"Process Development of the Synthetic Route to (<i>R</i>)-6-Amino-1-ethyl-4-methylhexahydro-1,4-diazepine","The optically active ( R )-6-amino-1-ethyl-4-methylhexahydro-1,4-diazepine ( 1) is the amine moiety of a novel and potent dopamine (D 2 and D 3 ) and 5-HT 3 receptors antagonist AS-8112, which is a clinical candidate expected to be a broad antiemetic agent. Process development of an effective synthetic route to the optically active amine 1 from N -Cbz- and N -Ts- l -serine methyl esters was undertaken. In two potential scale-up processes, the route from N -Ts- l -serine methyl ester ( 21 ) was chosen because of its better overall yield (>30% yield for seven steps) and handling. The optically active amine 1 with high purity (>99.5% ee) was prepared via the reaction of the key intermediate N -Ts-aziridine 23 with EtNH 2 and successive LiAlH 4 reduction without racemization. Moderate scale-up synthesis of the amine 1 and AS-8112 by condensation of 1 and 5-bromo-2-methoxy-6-methylaminopyridine-3-carboxylic acid is described.",10.1021/op010068e,2002-01-01,0.726703871863061
Organic Process Research & Development,Development of a Scalable Asymmetric Process for the Synthesis of Selective PDE4B Inhibitor Nerandomilast (BI 1015550),"A robust and scalable synthesis process for Nerandomilast ( 1, BI 1015550), a selective PDE4B inhibitor with potential therapeutic properties for the treatment of respiratory diseases, was developed and implemented at a pilot plant on a multikilogram scale. Key aspects of the process include the efficient synthesis of intermediate (1-((2-chloro-6,7-dihydrothieno[3,2- d ]pyrimidin-4-yl)amino)cyclobutyl)methanol ( 4 ) by means of a regioselective S N Ar reaction between (1-aminocyclobutyl)methanol ( 6 ) and 2,4-dichloro-6,7-dihydrothieno[3,2- d ]pyrimidine ( 5 ), a new convergent synthesis of 5-chloro-2-(piperidin-4-yl)pyrimidine ( 3 ) by means of a Suzuki coupling, and a highly enantioselective sulfide oxidation to give chiral nonracemic ( R )-2-chloro-4-((1-(hydroxymethyl)cyclobutyl)amino)-6,7-dihydrothieno[3,2- d ]pyrimidine 5-oxide ( 2 ).",10.1021/acs.oprd.4c00309,2024-09-05,0.7266293224891242
Organic Process Research & Development,Kilogram Synthesis of a LFA-1/ICAM Inhibitor,The process development and the kilogram-scale synthesis of BMS-587101 ( 1 ) are described. The synthesis features a [3 + 2] azomethine ylide cycloaddition to efficiently build the spirocyclic core in a diastereoselective fashion followed by a classical resolution which affords the desired enantiomer in >98% enantiomeric excess. The target was prepared in four steps in an overall yield of 22%.,10.1021/op9003168,2010-03-10,0.726589652350014
Organic Process Research & Development,A Practical Synthesis of Regioisomeric 6- and 7-Methoxytetrahydro-3-benzazepines,A concise and versatile synthetic route for 6- and 7-methoxy tetrahydro-3-benzazepines is described. The key feature of the synthesis is a one-pot acylation/cyclization/elimination sequence to construct either of the isomeric dihydrobenzazepine ring systems from the same starting material. The route is high yielding and chromatography-free.,10.1021/op900292j,2010-01-26,0.7265307759466118
Organic Process Research & Development,"Efficient Large-Scale Synthesis of a 2,4,5-Triarylimidazoline MDM2 Antagonist","An improved, kilogram-scale synthesis of a triarylimidazoline MDM2 antagonist is reported. The nicotinic acid component was prepared in three steps from ethyl 2-dimethylaminomethylene-3-oxo-butyrate. The coupling of the nicotinic acid with the meso -diamine selectively produced the monoamide which was cyclized in the presence of p -TSA/pyridine to give the imidazoline core. Phosgenation using bis(trichloromethyl) carbonate provided the key carbamoyl chloride intermediate, which was coupled with the side-chain amine, followed by chiral resolution with ( R )-camphorsulfonic acid to give the final API.",10.1021/op300294g,2012-11-20,0.7263560954546195
Organic Process Research & Development,Lab-Scale Preparation of a Novel Cyclopenta[b]furan Chemokine Receptor Antagonist,"The preparation of a chemokine receptor type 2 (CCR-2) antagonist bearing a cyclopenta[b]furan core is described on a 600 g scale. Compared to our previously reported synthesis of the all-carbon core CCR-2 antagonist with a similar peripheral 3-methoxypyran appendage, our work required a redesign of the original Discovery Chemistry route and took advantage of a side product seen in the diastereoselective alkylation reaction. Elaboration by reduction and oxy-cyclization eventually led to the required N -Boc acid method. After amidation using a traditional coupling reaction, a reductive amination using enantiomerically enriched 3-methoxy-4-pyranone led to the final compound. Although several steps of the syntheses involved reagents such as selenium and chromium that would not be used in a large-scale process setting, the overall route went through intermediates that could certainly be used for future scale-up campaigns. The synthesis provided a method to make lab-scale quantities of the final succinate salt to support tox/toleration studies. Relative to the Discovery Chemistry route, this lab-scale route featured novel intermediates that could open new avenues for future research in this area.",10.1021/op500266w,2014-11-10,0.7262360378612376
Organic Process Research & Development,An Improved Convergent Synthesis of AZD7762: A One-Pot Construction of a Highly Substituted Thiophene at the Multikilogram Scale,"A multikilogram synthesis of AZD7762 has been achieved using a highly convergent route employing two efficient telescoped sequences to generate the key intermediates. Aminothiophene 11 is formed in a four-step, one-pot addition–elimination–cyclization sequence from cinnamonitrile 9, constructing the trisubstituted thiophene ring with the desired API substitution pattern in place. Cinnamonitrile 9 is derived by elaboration of 3-fluoroacetophenone. Generation of the urea function, followed by deprotection, affords AZD7762 in 49% yield over 5 isolated stages from chiral piperidine 5, a 5-fold increase in yield versus the first generation route, reducing the starting material burden and eliminating the previous requirement for metal-mediated couplings and chromatography.",10.1021/acs.oprd.6b00364,2017-02-15,0.7260977524706904
Organic Process Research & Development,Development of the Large-Scale Preparation of 2-(Methanesulfonyl)benzenesulfonyl Chloride,"A practical and scalable process is described for the preparation of 2-(methansulfonyl)benzenesulfonyl chloride, a key building block used in the synthesis of several drug candidates. The material is prepared by an efficient four-step sequence from inexpensive 1,2-dichlorobenzene and methanethiol, and the process has been demonstrated on a multikilogram scale in 32% overall yield with a chemical purity of >98%.",10.1021/op2002744,2012-03-06,0.7260274232836345
Organic Process Research & Development,Development of a Scalable Synthesis for an Inhaled pan-JAK Inhibitor,"A scalable synthesis of a pan-JAK inhibitor is described. The original synthesis by the Medicinal Chemistry group has been modified to develop a new protecting group strategy, a 3-step telescoped synthesis to generate an imidazole ring from a nitrile, and a telescoped borylation/Suzuki coupling sequence as well as to replace HATU with process-friendly CDI in the final amidation step. Efficient API purification and polymorph interconversion protocols have been implemented to obtain API with the desired purity and physical properties for an inhaled formulation.",10.1021/acs.oprd.9b00253,2019-07-24,0.7260133266722892
Organic Process Research & Development,A Novel Scalable Process to the GSK3β Inhibitor AZD8926 Based on a Heterocyclic Ziegler Coupling,"Development of a new, safe, and scalable route to the GSK3β inhibitor, AZD8926, is presented. In brief, the process constitutes of (i) a synthesis of 1-(pyran-4-yl)-2-trifluoromethyl-imidazole, 14; (ii) a Ziegler-type coupling of lithiated 14 with commercially available 2-chloro-5-fluoropyrimidine via 1,2-addition over the 3,4-C–N bond; (iii) a copper-catalyzed dehydrogenative aromatization using oxygen as the stoichiometric oxidant; and (iv) an aromatic C–N bond formation using either a Buchwald–Hartwig coupling or an acid-catalyzed amination. This process circumvents the main issue in the early-phase route, in which serious process safety constraints were associated with the hazardous properties of the structure, formation, and reduction of 5-methyl-4-nitroisoxazole, 2 (4200 J/g). The new process has been demonstrated on a multigram, 2-L scale. The overall yield was improved from 4 to 14%, and the number of steps decreased from 12 to 10.",10.1021/op300365e,2013-03-22,0.7258176514004567
Organic Process Research & Development,"An Efficient Process for the Large-Scale Synthesis of a 2,3,6-Trisubstituted Indole","The efficient synthesis of a key trisubstituted indole intermediate 1 is described. The synthetic route required the use of an aryl Grignard reagent which was not commercially available, and the large-scale formation of this fragment and the thermal evaluation for this step is presented. The key step in the sequence was a Truce–Smiles rearrangement to provide an advanced ketone intermediate which, upon reduction, cyclized to the desired indole 1 . Design of experiment (DoE) optimization of this reduction is also presented. In total >50 kg of target indole 1 were synthesized in 55% overall yield over five steps using this new route.",10.1021/op300303p,2012-11-15,0.7256628683374897
Synthesis,"An Efficient Synthesis of 2,5-Diamino-1,4-benzoquinone","A novel and efficient synthesis of 2,5-diamino-1,4-benzoquinone is described. The reaction involves a palladium/charcoal hydrogenolysis as the key step and provides the desired product in only four steps and very good overall yield.",10.1055/s-2006-958945,2007-01-01,0.7253341531544302
Journal of Organic Chemistry,"Practical Synthesis of an Enantiomerically Pure <i>trans-</i>4,5-Disubstituted 2-Pyrrolidinone via Enzymatic Resolution. Preparation of the LTB<sub>4</sub> Inhibitor BIRZ-227","A practical synthesis of the enantiomerically pure BIRZ-227 ( 1 ), a LTB 4 inhibitor, has been developed. The key steps include the effective synthesis of the trans -diarylpyrrolidinone (±)- 8 and the enzymatic resolution of N -acetoxymethyl pyrrolidinone (±)- 10 by immobilized Lipase Novozym 435. Reduction of pyrrolidinone (+)- 8 with borane and subsequent coupling with chlorobenzoxazole 2 furnished BIRZ-227 in high enantiomeric purity (99% ee). The overall process described herein required no chromatographic separation and is amenable to the preparation of multikilogram quantities of the desired drug candidate in a cost-effective manner.",10.1021/jo971605p,1998-01-01,0.7251202045038446
Organic Process Research & Development,The Development of a Practical Multikilogram Synthesis of the Chiral β-Amino Acid Imagabalin Hydrochloride (PD-0332334) via Asymmetric Hydrogenation,"The development and implementation of a robust process for the manufacture of metric ton quantities of the α2δ ligand imagabalin hydrochloride 4 is described. Key aspects of the synthesis include a chromatography-free, two-step telescoped process to prepare a mixture of Z: E -enamides 7 followed by a robust asymmetric hydrogenation with the rhodium-trichickenfootphos catalyst 8 to install the (3 S )-stereocentre. Hydrolysis of the acetamide and ester protecting groups in the final step followed by isolation and recrystallisation of the hydrochloride salt gave high purity 4 in 40–50% overall yields.",10.1021/op2001639,2011-07-06,0.725089085896744
Organic Process Research & Development,"Rapid Development of a Commercial Process for Linrodostat, an Indoleamine 2,3-Dioxygenase (IDO) Inhibitor","The process development and the kilogram-scale synthesis of linrodostat (BMS-986205, 1 ) are described. The synthesis features several highly efficient telescoped processes and the use of Evans auxiliary to install a methyl-bearing stereocenter. The target was prepared in 12 steps with 7 isolations in an overall yield of 31%.",10.1021/acs.oprd.9b00359,2019-10-18,0.724854609119318
Organic Process Research & Development,Rapid Scale-Up of the Matrix Metalloproteinase Inhibitor CH5902:  Process Safety and Route Development Considerations,"The synthesis of the novel MMP inhibitor CH5902 is described. In this approach, the original discovery route has been streamlined and telescoped into a four-stage sequence, which has been demonstrated on a multikilogram scale. A number of issues arising from both process development and process safety concerns are discussed.",10.1021/op0340762,2003-08-30,0.7245439241491791
Organic Process Research & Development,Scalable Synthesis of 8-Amino-3-hydroxy-6<i>H</i>-benzo[<i>c</i>]chromen-6-one: Key Intermediate for SEGRA via the Hurtley Reaction,"A practical and scalable process for the preparation of 8-amino-3-hydroxy-6 H -benzo[ c ]chromen-6-one in multihundred kilogram amounts has been developed. The key features of this synthesis are the application of the Hurtley reaction with a copper and base combination and the development of a purification process. The new synthesis improved the total yield from 49.0% to 59.5% and reduced the number of steps from three to two. Compared with the conventional medicinal route, manufacturing costs were reduced significantly by the use of inexpensive, easy to procure materials.",10.1021/op500334b,2014-12-11,0.7245082543899113
Organic Letters,Total Synthesis of (−)-Leuconicine A and B,"Concise asymmetric total syntheses of Strychnos alkaloids (-)-leuconicine A (14 steps, 9% overall yield) and B (13 steps, 10% overall yield) have been accomplished. Key steps include (1) our sequential one-pot spiro-cyclization/intramolecular aza-Baylis-Hillman method to prepare the ABCE framework; (2) a novel domino acylation/Knoevenagel cyclization to prepare the F-ring; and (3) a Heck cyclization to access the D-ring.",10.1021/ol202056w,2011-08-03,0.7244169425079178
Tetrahedron,"Synthesis of 2-acetamido-1,2-dideoxy-d-galacto-nojirimycin [DGJNAc] from d-glucuronolactone: the first sub-micromolar inhibitor of α-N-acetylgalactosaminidases",,10.1016/j.tetlet.2010.02.063,2010-02-24,0.7244112544352812
Tetrahedron,"A new synthesis for 2-deoxy-KDO, a potent inhibitor of CMP=KDO synthetase",,10.1016/s0040-4039(00)73474-5,1994-09-01,0.7244070804456374
Organic Process Research & Development,Synthesis of an ORL-1 Receptor Antagonist via a Radical Bromination and Deoxyfluorination to Afford a <i>gem</i>-Difluorospirocycle,The development of a synthesis of an ORL-1 receptor antagonist is described. The key process improvements in the synthetic sequence include a multikilogram bromination process and the development of a convergent coupling strategy. The process improvements resulted in the production of the active pharmaceutical ingredient (API) on a multikilogram scale.,10.1021/op5000094,2014-08-04,0.724402703310026
Organic Process Research & Development,"Scalable Synthesis of C5aR1 Antagonist ACT-1014-6470 via <i>N</i><sup>7</sup>-Selective Reductive Amination of an Unprotected Pyrazole Starting Material and Intramolecular Urea Formation with 1,1′-Carbonyl-di(1,2,4-triazol) (CDT)","ACT-1014-6470 is a potent, orally available, reversible, and selective C5aR1 antagonist. Herein, we report the development of a scalable and robust process for the preparation of ACT-1014-6470 on kg scale. The synthetic sequence started from two inexpensive starting materials─ethyl 3-amino-1 H -pyrazole-4-carboxylate and 2-(trifluoromethyl)benzaldehyde─which were coupled together with a novel reductive amination protocol for electron-poor heterocycles that was perfectly N 7 -selective. After building up the core API-structure via a sequence of N 2 -pyrazole alkylation, ester hydrolysis, amide formation, and reduction, the final intramolecular urea formation was performed with a novel protocol using 1,1′-carbonyl-di(1,2,4-triazol), CDT. The cyclization worked under mild conditions at room temperature without the need of additional base and provided the API in high purity (99.4% a/a by HPLC, 99% w/w) after aqueous workup and crystallization from EtOH. In total, over 2.5 kg of ACT-1014-6470 were prepared in-house using the described 11-step synthesis, with the longest linear sequence (6 steps) having an overall yield of 42%.",10.1021/acs.oprd.3c00492,2024-02-08,0.7243933996902777
Angewandte Chemie International Edition,Synthesis of Apoptolidinone,"A CuI-mediated coupling of the northern and southern units and a ring-size selective macrolactonization are the key steps in the convergent, first total synthesis of apoptolidinone, the aglycon of the potential antitumor compound apoptolidin. (The wavey lines in the picture are the retrosynthetic disconnections.)",10.1002/1521-3773(20010601)40:11<2063::aid-anie2063>3.3.co;2-r,2001-06-01,0.7243862262555012
Angewandte Chemie International Edition,Synthesis of Apoptolidinone,"-mediated coupling of the northern and southern units and a ring-size selective macrolactonization are the key steps in the convergent, first total synthesis of apoptolidinone, the aglycon of the potential antitumor compound apoptolidin. (The wavey lines in the picture are the retrosynthetic disconnections.).",10.1002/1521-3773(20010601)40:11<2063::aid-anie2063>3.0.co;2-#,2001-05-28,0.7243862262555012
Tetrahedron,"An efficient new synthesis of 7-phthalimido-8--butoxy-5,8--desacetylcephalosporanic acid lactone, - a key intermediate in a total synthesis of the cephalosporins.",,10.1016/s0040-4039(01)85235-7,1972-01-01,0.7243755943805336
Organic Process Research & Development,Convergent Synthesis of a 5HT<sub>7</sub>/5HT<sub>2</sub> Dual Antagonist,"The development of an efficient and convergent route to 3-(4-fluorophenyl)-2-isopropyl-2,4,5,6,7,8-hexahydropyrazolo[3,4- d ]azepine ( 1 ), a potent 5HT 7 /5HT 2 dual antagonist, is described. Significant features of this route are: (a) a regioselective construction of a tetra-substituted pyrazole 6a by reacting an N -monosubstituted hydrazone 4a with an elaborated nitroolefin 5b and (b) a unique Pd-catalyzed hydrogenation method that carries out the four-step, ring-closing reductive amination sequence in a notable one-pot operation to provide 1 in excellent overall yields.",10.1021/op2001194,2011-05-31,0.7243701562919421
Tetrahedron,"An improved total synthesis of spermatinamine, an inhibitor of isoprenylcysteine carboxy methyltransferase",,10.1016/j.tetlet.2010.10.164,2010-11-05,0.7243567987488151
Organic Process Research & Development,Development of an Enantioselective Hydrogenation Route to (<i>S</i>)-1-(2-(Methylsulfonyl)pyridin-4-yl)propan-1-amine,"A highly enantioselective enamide hydrogenation route to the title amine was developed. Highlights of the synthesis include an efficient two-step synthesis of a 2-sulfonyl 4-pyridyl ethyl ketone, a simple enamide synthesis by direct condensation of propionamide with a ketone, catalytic asymmetric enamide hydrogenation employing the in-house-developed ligand MeO-BIBOP, and a mild epimerization-free deprotection of a propionamide using Koenig’s procedure.",10.1021/op5001513,2014-06-23,0.7243527385341932
European Journal of Organic Chemistry,Ring‐Closing Strategy Utilizing Nitrile α‐Anions: Chiral Synthesis of (+)‐Norchrysanthemic Acid and Expeditious Asymmetric Total Synthesis of (+)‐Grandisol,"Chiral syntheses of two distinct small cycloalkanes, (1 R ,3 R )‐(1 Z )‐norchrysanthemic acid and (+)‐grandisol, were performed by characteristic ring‐closing methodologies using carbanions at the α‐position of nitriles (nitrile α‐anions). (i) (1 R ,3 R )‐(1 Z )‐Norchrysanthemic acid, a highly potent ingredient of synthetic pyrethroid containing a cyclopropane structure, was synthesized from readily available ( S )‐epoxide derived from 3‐methyl‐but‐2‐en‐1‐ol in 7 steps in 23 % overall yield and with &gt; 98 % ee . This sequence involves a trans ‐selective cyclopropane formation using the nitrile α‐anion of ( S )‐3‐mesyloxynitrile as the key step. The present chiral synthesis was performed with effective stereocontrol of both the chirality in the 1,3‐positions on the cyclopropane and the Z ‐geometry of the propenyl group. (ii) (+)‐Grandisol, an insect sex pheromone possessing a characteristic cyclobutane structure, was synthesized from commercially available cyclopropyl methyl ketone (route A) or from commercially available 3‐cyanopropylzinc bromide and 1‐bromo‐1‐methylpropene (route B) in 10 or 8 steps in 6 % or 8 % overall yield and with 80 % ee . This sequence involves a Shi asymmetric epoxidation of a trisubstituted olefin and a straightforward Stork‐type asymmetric cyclobutane formation with clean S N 2 stereoinversion using the nitrile α‐anion of the chiral epoxynitrile. The present expedient method is the second asymmetric total synthesis starting from achiral compounds.",10.1002/ejoc.201801160,2018-09-21,0.7242366027618165
Journal of Organic Chemistry,"An Enantioselective Synthesis of an 11-β-HSD-1 Inhibitor via an Asymmetric Methallylation Catalyzed by (<i>S</i>)-3,3′-F<sub>2</sub>-BINOL","An efficient asymmetric synthesis of 11-β-HSD inhibitor 1 has been accomplished in five linear steps and 53% overall yield, starting from the readily available 3-chloro-1-phenylpropan-1-one. The key feature of the synthesis includes an asymmetric methallylation of 3-chloro-1-phenylpropan-1-one catalyzed by the highly effective organocatalyst (S)-3,3'-F2-BINOL under solvent-free and metal-free conditions.",10.1021/acs.joc.6b00189,2016-02-24,0.7241122176255376
Organic Process Research & Development,Development of a Scalable Synthesis of an Azaindolyl-Pyrimidine Inhibitor of Influenza Virus Replication,"A scalable, asymmetric route for the synthesis of the influenza virus replication inhibitor 2 is presented. The key steps include an enzymatic desymmetrization of cis -1,3-cyclohexanediester in 99% yield and 96% ee, S N Ar displacement of a methanesulfinylpyrimidine, and a Curtius rearrangement to form a morpholinyl urea. This high-yielding route allowed us to rapidly synthesize hundreds of grams of 2 in 99% purity to support in vivo studies.",10.1021/acs.oprd.6b00063,2016-04-08,0.7240807292824643
Tetrahedron,"Synthesis of P1,P2-dinucleotide pyrophosphates",,10.1016/s0040-4039(00)96203-8,1987-01-01,0.7240642786185283
Tetrahedron,The synthesis of epoxypiperolides and piperolides,,10.1016/s0040-4039(00)84091-5,1986-01-01,0.7240642786185283
Tetrahedron,Serendipitous synthesis of trimetallic porphyrazine triads,,10.1016/j.tetlet.2009.06.120,2009-07-03,0.7240642786185283
Tetrahedron,"Synthesis of -myo-inositol 1,4,5-triphosphate",,10.1016/s0040-4039(00)96111-2,1987-01-01,0.7240642786185283
Tetrahedron,Synthesis of erythroxydiol a (hydroxymonogynol),,10.1016/s0040-4039(01)98453-9,1970-01-01,0.7240642786185283
Tetrahedron,Synthesis of (±)-7-oxaprostaglandin E1,,10.1016/s0040-4039(01)98315-7,1970-01-01,0.7240642786185283
Tetrahedron,A biomimetic synthesis of polycyclic quinones,,10.1016/s0040-4039(00)96034-9,1987-01-01,0.7240642786185283
Tetrahedron,"Synthesis of 1,8-dioxooctahydroxanthene C-nucleosides",,10.1016/j.tetlet.2013.05.067,2013-05-24,0.7240642786185283
Tetrahedron,"Synthesis of porphyrins with four exocyclic rings from 4,5,6,7-tetrahydroindoles",,10.1016/s0040-4039(00)95308-5,1987-01-01,0.7240642786185283
Tetrahedron,"Synthesis of 1,2-O-isopropylidene-α-D-apio-D-furanose and D-apiose",,10.1016/s0040-4039(01)87967-3,1969-01-01,0.7240642786185283
Tetrahedron,"Synthesis of 1-, 2-, and 6-Azulenethiols",,10.1016/s0040-4039(01)93890-0,1989-01-01,0.7240642786185283
Tetrahedron,The synthesis of -prostaglandin E1 methoxime,,10.1016/s0040-4039(01)88770-0,1969-01-01,0.7240642786185283
Synthesis,Organometallics in Synthesis (A Manual),,10.1055/s-2002-33329,2002-01-01,0.7240642786185283
Tetrahedron,"A synthesis of 160β, 17β-iminoandrostanes",,10.1016/s0040-4039(01)88025-4,1969-01-01,0.7240642786185283
Tetrahedron,A synthesis of dl-methylmycaminoside,,10.1016/s0040-4039(01)88705-0,1969-01-01,0.7240642786185283
Tetrahedron,Synthesis of phenoxyacetyl-N-sulphonyl cycloserine,,10.1016/s0040-4039(00)96496-7,1987-01-01,0.7240642786185283
Tetrahedron,Synthesis of unsymmetrical spin-labelled bolaamphiphiles,,10.1016/j.tetlet.2008.05.125,2008-06-03,0.7240642786185283
Tetrahedron,Synthesis of the barbaralone nucleus via photocyclization of an alkynyl tropone,,10.1016/s0040-4039(00)95792-7,1987-01-01,0.7240642786185283
Tetrahedron,Synthesis of Δ1 and Δ1(6) tetrahydrocannabinol metabolites,,10.1016/s0040-4039(01)83959-9,1970-01-01,0.7240642786185283
Tetrahedron,Formal synthesis of semiaquilegin A,,10.1016/j.tetlet.2009.12.118,2009-12-29,0.7240642786185283
Tetrahedron,The synthesis of pyoluteorin,,10.1016/s0040-4039(01)98526-0,1970-01-01,0.7240642786185283
Tetrahedron,The synthesis of 1-azatwistane,,10.1016/s0040-4039(01)87574-2,1970-01-01,0.7240642786185283
Tetrahedron,The synthesis of samane (desoxysamanine) and 17β-hydroxysamane,,10.1016/s0040-4039(01)87839-4,1969-01-01,0.7240642786185283
Tetrahedron,Stereocontrolled synthesis of diamines from iodolactams,,10.1016/s0040-4039(00)95474-1,1987-01-01,0.7240642786185283
Tetrahedron,"Synthesis of 1,1-diarylcyclopentanetetrone hydrates",,10.1016/s0040-4039(01)98005-0,1970-01-01,0.7240642786185283
Tetrahedron,Synthesis of lachnanthocarpone,,10.1016/s0040-4039(01)98214-0,1970-01-01,0.7240642786185283
Tetrahedron,The synthesis of Irisquinone,,10.1016/s0040-4039(01)80507-4,1989-01-01,0.7240642786185283
Tetrahedron,Synthesis of isoajmaline,,10.1016/s0040-4039(01)97692-0,1969-01-01,0.7240642786185283
Tetrahedron,"Synthesis of DL--inositol 1,4,5-triphosphate",,10.1016/s0040-4039(00)96110-0,1987-01-01,0.7240642786185283
Tetrahedron,Synthesis of furans by carbene insertion,,10.1016/s0040-4039(00)96071-4,1987-01-01,0.7240642786185283
Tetrahedron,"Synthesis of 4-, 5-, 6-, and 7-azidotryptamines",,10.1016/j.tetlet.2008.10.091,2008-11-12,0.7240642786185283
Tetrahedron,Synthesis of azacyclic 2-deoxy-KDO,,10.1016/s0040-4039(01)80986-2,1987-01-01,0.7240642786185283
Tetrahedron,Synthesis of lonapalene,,10.1016/s0040-4039(00)96549-3,1987-01-01,0.7240642786185283
Tetrahedron,A synthesis of forskolin. Hydroxylation of 9-deoxyforskolin.,,10.1016/s0040-4039(00)95638-7,1987-01-01,0.7240642786185283
Tetrahedron,Synthesis of spider toxin (JSTX-3) and its analogs,,10.1016/s0040-4039(00)96340-8,1987-01-01,0.7240642786185283
Tetrahedron,The synthesis of(±)-dictyopterene a,,10.1016/s0040-4039(01)88420-3,1969-01-01,0.7240642786185283
Tetrahedron,The synthesis of (±)-cavernosine,,10.1016/s0040-4039(01)83856-9,1987-01-01,0.7240642786185283
Tetrahedron,A Wacker–Cook synthesis of isoflavones: formononetine,,10.1016/j.tetlet.2009.01.041,2009-01-15,0.7240642786185283
Tetrahedron,"Photocyclizations of 5-acylnorbornenes; A synthesis of tricyclo [3.3.0.0.3,7]octan-2-ols",,10.1016/s0040-4039(01)88209-5,1969-01-01,0.7240642786185283
Tetrahedron,Synthesis of 2′-deoxy-2′-mercaptouridine,,10.1016/s0040-4039(00)89352-1,1970-01-01,0.7240642786185283
Tetrahedron,Synthesis of β-heteroaryl propionates via trapping of carbocations with π-nucleophiles,,10.1016/j.tetlet.2009.02.018,2009-02-09,0.7240642786185283
Tetrahedron,"Synthesis of (±)-talaromycins A, B, C and E",,10.1016/s0040-4039(00)95297-3,1989-01-01,0.7240642786185283
Tetrahedron,Synthesis of calix[4]arenes presenting no plane of symmetry,,10.1016/s0040-4039(00)96922-3,1987-01-01,0.7240642786185283
Tetrahedron,Synthesis of anthracycline C-glycosyl isosteres,,10.1016/s0040-4039(00)94243-6,1986-01-01,0.7240642786185283
Tetrahedron,Synthesis of (±)-isoprosopinines A and B,,10.1016/s0040-4039(01)80997-7,1987-01-01,0.7240642786185283
Tetrahedron,Synthesis of polyfunctionalized acylsilanes via propenoyltrimethylsilane.,,10.1016/s0040-4039(01)83870-3,1987-01-01,0.7240642786185283
Tetrahedron,Synthesis of girinimbine and (±) mahanimbine,,10.1016/s0040-4039(01)98049-9,1970-01-01,0.7240642786185283
Tetrahedron,Synthesis of oxabetweenallenes,,10.1016/s0040-4039(00)85078-9,1986-01-01,0.7240642786185283
Tetrahedron,The synthesis of 1-azatwistane,,10.1016/s0040-4039(01)87573-0,1970-01-01,0.7240642786185283
Tetrahedron,Synthesis of (S)-ktedonoketone,,10.1016/j.tetlet.2020.151915,2020-04-04,0.7240642786185283
Tetrahedron,Synthesis of luciferin,,10.1016/s0040-4039(01)88584-1,1969-01-01,0.7240642786185283
Tetrahedron,Synthesis of threonine phosphoglycerides,,10.1016/s0040-4039(00)89448-4,1970-01-01,0.7240642786185283
Tetrahedron,Synthesis of 2-aminocyclopropyl pyrrolidines from glycoaminonitriles,,10.1016/j.tetlet.2009.02.135,2009-02-26,0.7240642786185283
Tetrahedron,Synthesis of dehydroxymethylbulgecin a,,10.1016/s0040-4039(01)81081-9,1987-01-01,0.7240642786185283
Tetrahedron,The synthesis of a tricyclic hydroazulenone from exo-epoxygermacrene-Din connection with periplanone A,,10.1016/s0040-4039(00)96398-6,1987-01-01,0.7240642786185283
Tetrahedron,"Synthesis of S-cysteinyl, S(N-acetylcysteinyl) and S-glutathionyl conjugates op N-hydroxymethyltriazenes",,10.1016/0040-4039(88)85266-3,1988-01-01,0.7240642786185283
Tetrahedron,"Synthesis of tribenzo-1,6-diazabicyclo[4.4.4]tetradecane",,10.1016/j.tetlet.2024.155065,2024-04-17,0.7240642786185283
Tetrahedron,Synthesis of (1Z)-deacylcnicin,,10.1016/j.tetlet.2022.154102,2022-08-27,0.7240642786185283
Tetrahedron,Synthesis of 3-arylated indolines from dearomatization of indoles,,10.1016/j.tetlet.2015.05.078,2015-05-29,0.7240642786185283
Tetrahedron,Synthesis of (±)duryne,,10.1016/s0040-4039(00)99632-1,1989-01-01,0.7240642786185283
Tetrahedron,Synthesis of diaryl squaraines and diaryl maleimides,,10.1016/j.tetlet.2025.155796,2025-08-20,0.7240642786185283
Tetrahedron,Synthesis of the spirocyclic alkaloid nitramine,,10.1016/s0040-4039(00)84882-0,1986-01-01,0.7240642786185283
Tetrahedron,A synthesis of -2-arylbenzocyclobuten-1-ols,,10.1016/s0040-4039(00)84495-0,1986-01-01,0.7240642786185283
Tetrahedron,"First synthesis of 1,3-oxaselenepanes",,10.1016/j.tetlet.2009.04.004,2009-04-08,0.7240642786185283
Tetrahedron,Synthesis of oudehansins A and B,,10.1016/s0040-4039(00)84551-7,1986-01-01,0.7240642786185283
Tetrahedron,The synthesis of 1-alkylthiopyrroles,,10.1016/s0040-4039(00)85039-x,1986-01-01,0.7240642786185283
Tetrahedron,A formal synthesis of bruceantin,,10.1016/s0040-4039(00)95200-6,1989-01-01,0.7240642786185283
Tetrahedron,Formal synthesis of (±)-ganocins B and C,,10.1016/j.tetlet.2025.155776,2025-08-05,0.7240642786185283
Tetrahedron,The first synthesis of marine sesterterpene (+)-scalarolide,,10.1016/j.tetlet.2009.06.064,2009-06-17,0.7240642786185283
Tetrahedron,A multicomponent synthesis of gem-(β-dicarbonyl)arylmethanes,,10.1016/j.tetlet.2009.05.033,2009-05-19,0.7240642786185283
Tetrahedron,Synthesis of a presumed sex attractant of the dried bean beetle,,10.1016/s0040-4039(01)94159-0,1972-01-01,0.7240642786185283
Tetrahedron,Synthesis of uliginosin B.,,10.1016/s0040-4039(01)94428-4,1972-01-01,0.7240642786185283
Tetrahedron,The synthesis of (±)-dubinidine,,10.1016/s0040-4039(01)87538-9,1971-01-01,0.7240642786185283
Tetrahedron,A regiocontrolled synthesis of allylstannanes,,10.1016/s0040-4039(00)85226-0,1986-01-01,0.7240642786185283
Tetrahedron,Synthesis of 1-vinylpyrrole-2-carbonitriles,,10.1016/j.tetlet.2008.10.104,2008-10-26,0.7240642786185283
Tetrahedron,Synthesis of tetrahydroseleno-1 and telluro-1 pyranones-4,,10.1016/s0040-4039(00)98229-7,1985-01-01,0.7240642786185283
Tetrahedron,Enantiodivergent synthesis of (−)-methylenolactocin and (+)-methylenolactocin from d-mannitol,,10.1016/j.tetlet.2009.10.011,2009-10-09,0.7240642786185283
Tetrahedron,"Synthesis of -(3S,4S)-dibenzyloxycyclopentanone",,10.1016/s0040-4039(00)98633-7,1985-01-01,0.7240642786185283
Journal of Organic Chemistry,Synthesis of steroid phosphates via monomeric metaphosphate,,10.1021/jo00157a005,1983-05-01,0.7240642786185283
Tetrahedron,"Iodocyclization of S–(homo)propargyl dithiocarbamates: Regiospecific synthesis of 2-imino(iminium)-1, 3-dithiolanes/dithianes/dithiepanes",,10.1016/j.tetlet.2023.154702,2023-08-12,0.7240642786185283
Tetrahedron,Synthesis of a diquinocyclobutene,,10.1016/s0040-4039(01)84652-9,1972-01-01,0.7240642786185283
Tetrahedron,Synthesis of pyrazomycin,,10.1016/s0040-4039(01)84827-9,1972-01-01,0.7240642786185283
Tetrahedron,Marine cembranoid synthesis,,10.1016/s0040-4039(01)80645-6,1989-01-01,0.7240642786185283
Tetrahedron,"Synthesis of 3-(N,N-dimethylamino)-2H-1-benzopyran-2-one",,10.1016/s0040-4039(00)99561-3,1989-01-01,0.7240642786185283
Tetrahedron,Synthesis of (±)--methylaversin,,10.1016/s0040-4039(01)96568-2,1971-01-01,0.7240642786185283
Tetrahedron,"The synthesis of 4,5-benzohomotropone",,10.1016/s0040-4039(01)96367-1,1971-01-01,0.7240642786185283
Tetrahedron,"Pyrolysis of 2-azido-1, 3-indanediones. Azanaphthoquinone synthesis",,10.1016/s0040-4039(01)87417-7,1971-01-01,0.7240642786185283
Tetrahedron,"Synthesis of [6] (2,4)heterophanes",,10.1016/s0040-4039(01)96642-0,1971-01-01,0.7240642786185283
Tetrahedron,A convinient synthesis of toxoflavins and toxoflavin-n-oxides,,10.1016/s0040-4039(01)96572-4,1971-01-01,0.7240642786185283
Tetrahedron,A synthesis of the Hirsutane skeleton,,10.1016/0040-4039(71)80007-2,1971-01-01,0.7240642786185283
Tetrahedron,"Synthesis of (±)-ircinianin, a marine sponge sesterterpene",,10.1016/s0040-4039(00)83911-8,1986-01-01,0.7240642786185283
Tetrahedron,"Synthesis of 2,2a1,6-Triazaaceanthrylenes",,10.1016/j.tetlet.2023.154834,2023-11-15,0.7240642786185283
Tetrahedron,The synthesis of 4-desoxy-2-azapodophyllotoxins,,10.1016/s0040-4039(01)80681-x,1989-01-01,0.7240642786185283
Tetrahedron,Synthesis of 4-methylene-1-cyclopentenes,,10.1016/s0040-4039(00)84281-1,1986-01-01,0.7240642786185283
Tetrahedron,Synthesis of maturone,,10.1016/s0040-4039(00)83921-0,1986-01-01,0.7240642786185283
Tetrahedron,"Synthesis of (±)-prepinnaterpene, a bromoditerpene from the red alga Yamada",,10.1016/s0040-4039(00)96491-8,1987-01-01,0.7240642786185283
Tetrahedron,Tremorgenic mycotoxins: synthesis of 6-demethoxyfumitremorgin C,,10.1016/s0040-4039(00)95307-3,1987-01-01,0.7240642786185283
Tetrahedron,"The synthesis of dihydrofurano[2,3-b]thiopyrans, thiepins and thiophenes",,10.1016/s0040-4039(00)70630-7,1989-01-01,0.7240642786185283
Tetrahedron,Synthesis of (+)-α-eudesmol,,10.1016/s0040-4039(00)90313-7,1966-01-01,0.7240642786185283
Tetrahedron,Synthesis of illudin S,,10.1016/s0040-4039(01)96777-2,1971-01-01,0.7240642786185283
Tetrahedron,A synthesis of 2′-deoxy-l-uridine,,10.1016/s0040-4039(01)96393-2,1971-01-01,0.7240642786185283
Tetrahedron,Synthesis of brachycoumarin and cyclobrachycoumarin,,10.1016/s0040-4039(00)85210-7,1986-01-01,0.7240642786185283
Tetrahedron,"A synthesis of -2, 3, 4, 5, 6-penta--benzylmyoinositol",,10.1016/s0040-4039(00)75669-3,1966-01-01,0.7240642786185283
Tetrahedron,Synthesis of 3-heterosubstituted isocephem and iso-oxacephem antibiotics,,10.1016/s0040-4039(00)84003-4,1986-01-01,0.7240642786185283
Tetrahedron,"3,3,3′,3′-tetramethyl-2,2′-bistrimethylsilyl-1,1′-bicyclopropenyl: Synthesis and isomerization",,10.1016/s0040-4039(00)84313-0,1986-01-01,0.7240642786185283
Tetrahedron,"An enantiospecific synthesis of (-)-(5R,6S)-6-acetoxy-5-hexadecanolide, the mosquito oviposition attractant pheromone",,10.1016/s0040-4039(01)80298-7,1989-01-01,0.7240642786185283
Tetrahedron,Synthesis of germathiiranes,,10.1016/s0040-4039(00)84766-8,1986-01-01,0.7240642786185283
Tetrahedron,The synthesis of nigrifactin,,10.1016/s0040-4039(01)98319-4,1970-01-01,0.7240642786185283
Tetrahedron,Synthesis of ]-cycleanine,,10.1016/s0040-4039(00)76044-8,1966-01-01,0.7240642786185283
Tetrahedron,Synthesis of (pentacarbonyl)tungstate(−1) and (pentacarbonyl)molybdate(−1) dinucleotides,,10.1016/j.tetlet.2009.06.089,2009-06-22,0.7240642786185283
Tetrahedron,An expeditious synthesis of anthracyclines,,10.1016/s0040-4039(00)84546-3,1986-01-01,0.7240642786185283
Tetrahedron,Synthesis of the chromophore of rubrolone,,10.1016/s0040-4039(00)85395-2,1986-01-01,0.7240642786185283
Tetrahedron,Synthesis of showdomycin,,10.1016/s0040-4039(01)98213-9,1970-01-01,0.7240642786185283
Tetrahedron,"The synthesis of a 1,4-dithiocin",,10.1016/s0040-4039(01)97066-2,1971-01-01,0.7240642786185283
Tetrahedron,"Synthesis of deoxypolyoxin C, “ thymine polyoxin C ”",,10.1016/s0040-4039(01)97416-7,1971-01-01,0.7240642786185283
Tetrahedron,The synthesis of fused triazolo-oxadiazoles,,10.1016/s0040-4039(01)87446-3,1971-01-01,0.7240642786185283
Tetrahedron,"Synthesis of a 1,3,4,5-tetrahydrobenzindole β-ketoester",,10.1016/j.tetlet.2009.09.032,2009-09-11,0.7240642786185283
Tetrahedron,Synthesis of the “tricyclic heart” of manzamines,,10.1016/s0040-4039(00)99482-6,1989-01-01,0.7240642786185283
Tetrahedron,Synthesis of bruceantin skeleton,,10.1016/s0040-4039(00)84809-1,1986-01-01,0.7240642786185283
Tetrahedron,A biomimetic synthesis of (±)-nanaomycin A,,10.1016/s0040-4039(00)97504-x,1990-01-01,0.7240642786185283
Tetrahedron,Synthesis of (±)-solanapyrone A,,10.1016/s0040-4039(00)95319-x,1987-01-01,0.7240642786185283
Tetrahedron,A synthesis of steviol,,10.1016/s0040-4039(01)98674-5,1970-01-01,0.7240642786185283
Tetrahedron,"Synthesis of some polycyclic quinones through 1-methoxycyclohexa-1,3-dienes",,10.1016/s0040-4039(01)98504-1,1970-01-01,0.7240642786185283
Tetrahedron,Synthesis of the steroidal alkaloid solanocapsine,,10.1016/s0040-4039(00)99986-6,1970-01-01,0.7240642786185283
Tetrahedron,Synthesis of yangonole,,10.1016/0040-4039(70)80083-1,1970-01-01,0.7240642786185283
Tetrahedron,Arsonium ylides in the synthesis of indoles,,10.1016/s0040-4039(00)89410-1,1970-01-01,0.7240642786185283
Tetrahedron,Synthesis of the hexahydrobenzofuran subunit of the milbemycins and the avermectins,,10.1016/s0040-4039(00)83999-4,1986-01-01,0.7240642786185283
Tetrahedron,Rational synthesis of deuterium-labelled pyridoxal and pyridoxyl alkaloids,,10.1016/s0040-4039(00)83970-2,1986-01-01,0.7240642786185283
Tetrahedron,Synthesis of lipoxin b,,10.1016/s0040-4039(00)84105-2,1986-01-01,0.7240642786185283
Tetrahedron,"Synthesis of D-myo-inositol 1,3,4,5-tetrakisphosphate",,10.1016/s0040-4039(00)96599-7,1987-01-01,0.7240642786185283
Tetrahedron,"Synthesis of 2′(S), 3′(R),5′-trihydroxypentyladenine",,10.1016/s0040-4039(00)86662-9,1988-01-01,0.7240642786185283
Tetrahedron,"Synthesis of a limonoid, azadiradione",,10.1016/s0040-4039(00)99392-4,1989-01-01,0.7240642786185283
Tetrahedron,A synthesis of (−)-tetrahydrolipstatin,,10.1016/s0040-4039(00)99592-3,1989-01-01,0.7240642786185283
Tetrahedron,Synthesis of butenolides as seed germination stimulants,,10.1016/j.tetlet.2008.03.024,2008-03-10,0.7240642786185283
Tetrahedron,Synthesis of 3H-labeled Efomycine M,,10.1016/j.tetlet.2007.06.130,2007-06-28,0.7240642786185283
Tetrahedron,"Synthesis and photoreactivity of some 5-alkylidene- and 5-alkylidenamine-2,5-dihydroisoxazoles",,10.1016/j.tetlet.2007.11.195,2007-12-05,0.7240642786185283
Tetrahedron,Synthesis of hormothamnione,,10.1016/s0040-4039(00)80196-3,1988-01-01,0.7240642786185283
Tetrahedron,Synthesis of 13C- and 2H-labelled PQQ,,10.1016/s0040-4039(00)82160-7,1988-01-01,0.7240642786185283
Tetrahedron,"Synthesis of 1,2,3-triphenyl-4-azaazulene",,10.1016/s0040-4039(01)98313-3,1970-01-01,0.7240642786185283
Tetrahedron,Synthesis of trioxilin B3,,10.1016/s0040-4039(00)80463-3,1988-01-01,0.7240642786185283
Tetrahedron,Synthesis of elaiolide and halichoblelide aglycone,,10.1016/j.tetlet.2019.04.032,2019-04-23,0.7240642786185283
Tetrahedron,Synthesis of phosphonosphingoglycolipid found in marine snail turbo cornutus,,10.1016/s0040-4039(00)86684-8,1988-01-01,0.7240642786185283
Tetrahedron,Synthesis of unsymmetrical saturated or diacetylenic cationic bolaamphiphiles,,10.1016/j.tetlet.2008.10.073,2008-10-22,0.7240642786185283
Tetrahedron,An enantiospecific synthesis of the spiroketal portion of avermectin B1a,,10.1016/0040-4039(88)85048-2,1988-01-01,0.7240642786185283
Tetrahedron,Stereocontrolled synthesis of the spirocyclic alkaloid (±)-nitramine,,10.1016/s0040-4039(00)82382-5,1988-01-01,0.7240642786185283
Tetrahedron,"Synthesis of silylated 1,3-dienes via the carbopalladation of allenes.",,10.1016/s0040-4039(00)80167-7,1988-01-01,0.7240642786185283
Tetrahedron,"Synthesis of oleandomycin through the intact aglycone, oleandolide",,10.1016/s0040-4039(00)80397-4,1988-01-01,0.7240642786185283
Synthesis,The Synthesis of Macrocyclic Musks,,10.1055/s-1999-3581,1999-10-01,0.7240642786185283
Tetrahedron,A synthesis of the C1–C15 domain of the halichondrins,,10.1016/j.tetlet.2008.03.018,2008-03-10,0.7240642786185283
Tetrahedron,Synthesis of a library of glycosylated flavonols,,10.1016/j.tetlet.2008.10.032,2008-10-14,0.7240642786185283
Tetrahedron,Synthesis of 2-azapodophyllotoxin,,10.1016/s0040-4039(00)95275-4,1989-01-01,0.7240642786185283
Tetrahedron,Synthesis and chiroptical property of C2-symmetric cyclohexapyrrole,,10.1016/j.tetlet.2007.01.004,2007-01-08,0.7240642786185283
Tetrahedron,Synthesis of d1-cepharanthine,,10.1016/s0040-4039(00)90667-1,1967-01-01,0.7240642786185283
Tetrahedron,Synthesis of a C3-symmetric phospha[2.2.2]cyclophane,,10.1016/s0040-4039(00)80690-5,1988-01-01,0.7240642786185283
Tetrahedron,Synthesis of methylene bridged C-disaccharides,,10.1016/s0040-4039(00)80300-7,1988-01-01,0.7240642786185283
Tetrahedron,The synthesis of dehydrobufotenine,,10.1016/s0040-4039(00)90995-x,1967-01-01,0.7240642786185283
Tetrahedron,Synthesis of dinucleoside phosphorodithioates via thioamidites,,10.1016/s0040-4039(00)80801-1,1988-01-01,0.7240642786185283
Tetrahedron,Versatility of 2-oxobenzo[h]chromene for the synthesis of oxabenzo[c]chrysenes,,10.1016/j.tetlet.2007.02.106,2007-03-01,0.7240642786185283
Journal of the American Chemical Society,Synthesis of Blaryls,,,2005-01-01,0.7240642786185283
Tetrahedron,Enantiospecific synthesis of (+)-hernandulcin,,10.1016/j.tetlet.2008.06.066,2008-06-19,0.7240642786185283
Tetrahedron,Synthesis of oxygenated 2-methylindolines,,10.1016/j.tetlet.2014.03.095,2014-03-28,0.7240642786185283
Tetrahedron,Synthesis of chromanyl and dihydrobenzofuranyl piperazines,,10.1016/j.tetlet.2007.02.121,2007-03-02,0.7240642786185283
Tetrahedron,"Synthesis of semi-saturated polycyclic 1,2,4-triazoles from lactams",,10.1016/j.tetlet.2021.153397,2021-09-06,0.7240642786185283
Tetrahedron,Synthesis of the C11-C28 subunit of the avermectins,,10.1016/s0040-4039(00)86686-1,1988-01-01,0.7240642786185283
Tetrahedron,"Synthesis of spheroidene, spheroidenone, and “P518”",,10.1016/s0040-4039(00)76265-4,1966-01-01,0.7240642786185283
Tetrahedron,First synthesis of agelasidine A,,10.1016/s0040-4039(00)80651-6,1988-01-01,0.7240642786185283
Tetrahedron,Synthesis of mangiferin,,10.1016/s0040-4039(01)99040-9,1968-01-01,0.7240642786185283
Tetrahedron,"The synthesis of 1,4-dihydroxy- and 1,4-dihalogenobicyclo[2.2.2]octanes",,10.1016/s0040-4039(01)89746-x,1967-01-01,0.7240642786185283
Tetrahedron,"Synthesis of 9-(3-azido-2,3-dideoxy-β-D--pentofuranosyl)-2,6-diaminopurine (AzddDAP)",,10.1016/s0040-4039(01)80635-3,1989-01-01,0.7240642786185283
Tetrahedron,Towards paspalicine : Synthesis of rings D-G,,10.1016/s0040-4039(00)99200-1,1989-01-01,0.7240642786185283
Tetrahedron,Synthesis of hexaoxadiamantanes,,10.1016/s0040-4039(00)72956-x,1966-01-01,0.7240642786185283
Tetrahedron,Synthesis of 5-(D-ribofuranosyl)-6-azauracil,,10.1016/s0040-4039(01)99924-1,1966-01-01,0.7240642786185283
Tetrahedron,Synthesis of hinokiflavone,,10.1016/s0040-4039(01)89648-9,1967-01-01,0.7240642786185283
Tetrahedron,Fungus pigments XVII The synthesis of phlebiarubrone,,10.1016/s0040-4039(00)90248-x,1966-01-01,0.7240642786185283
Tetrahedron,"Synthesis of 1,2′- and 1,3′-bipyrroles from 2- and 3-nitropyrroles",,10.1016/j.tetlet.2008.04.025,2008-04-07,0.7240642786185283
Tetrahedron,Synthesis of β-elemene and elemol,,10.1016/s0040-4039(00)90811-6,1967-01-01,0.7240642786185283
Tetrahedron,"The synthesis of 1-methyltricyclo[4.4.0.02,7]decanes",,10.1016/s0040-4039(00)76293-9,1966-01-01,0.7240642786185283
Tetrahedron,Chichibabin “isodesmopyridine” synthesis,,10.1016/j.tetlet.2019.02.038,2019-02-22,0.7240642786185283
Tetrahedron,The synthesis of 2-azapodophyllotoxins,,10.1016/s0040-4039(01)80682-1,1989-01-01,0.7240642786185283
Tetrahedron,"Synthesis of Macrobicyclic Cryptates incorporating Bithiazole, Bisimidazole and Bipyrimidine Binding Subunits",,10.1016/s0040-4039(00)99650-3,1989-01-01,0.7240642786185283
Tetrahedron,Synthesis of strophanthidin,,10.1016/s0040-4039(01)80714-0,1989-01-01,0.7240642786185283
Tetrahedron,"Synthesis of benzimidazoles from 1,1-dibromoethenes",,10.1016/j.tetlet.2008.10.030,2008-10-15,0.7240642786185283
Tetrahedron,Synthesis of vinylcyclophopane,,10.1016/s0040-4039(00)62019-1,1966-01-01,0.7240642786185283
Tetrahedron,Synthesis of three stereoisomers of 2-deoxystreptamine,,10.1016/s0040-4039(00)71567-x,1967-01-01,0.7240642786185283
Tetrahedron,Synthesis of hormothamnione,,10.1016/s0040-4039(00)86056-6,1988-01-01,0.7240642786185283
Tetrahedron,The synthesis of riccardin C,,10.1016/s0040-4039(00)80674-7,1988-01-01,0.7240642786185283
Tetrahedron,Synthesis of (±) silphinene,,10.1016/0040-4039(88)80029-7,1988-01-01,0.7240642786185283
Tetrahedron,A synthesis of zoapatanol,,10.1016/0040-4039(88)85233-x,1988-01-01,0.7240642786185283
Tetrahedron,Synthesis of perlolidine,,10.1016/s0040-4039(01)84129-0,1966-01-01,0.7240642786185283
Tetrahedron,A prostaglandin synthesis,,10.1016/s0040-4039(00)91020-7,1967-01-01,0.7240642786185283
Tetrahedron,"Synthesis of [4,4,4] propellane",,10.1016/s0040-4039(00)90590-2,1967-01-01,0.7240642786185283
Tetrahedron,Synthesis of diazomercurials,,10.1016/s0040-4039(00)89831-7,1968-01-01,0.7240642786185283
Tetrahedron,"Synthesis of hybrids between the alkaloids rutaecarpine and luotonins A, B",,10.1016/j.tetlet.2008.05.141,2008-06-05,0.7240642786185283
Tetrahedron,The synthesis of codeine and morphine glucoronides,,10.1016/s0040-4039(01)98789-1,1968-01-01,0.7240642786185283
Tetrahedron,"Synthesis and photo-isomerisation of 7,8-diphenyl-2,3-benzobicyclo[4.2.0]octa-2,4,7-triene and 4,5-diphenylbenzocyclo-octatetraene",,10.1016/s0040-4039(01)99030-6,1968-01-01,0.7240642786185283
Tetrahedron,The synthesis of volatile lactones,,10.1016/s0040-4039(00)82167-x,1988-01-01,0.7240642786185283
Tetrahedron,Synthesis of hydroxyisoxazolidines on adsorbents,,10.1016/s0040-4039(01)80339-7,1989-01-01,0.7240642786185283
Tetrahedron,"Synthesis of 1,3,4,6,7,9-hexamethylphenalene",,10.1016/s0040-4039(00)90716-0,1967-01-01,0.7240642786185283
Tetrahedron,Aminocyclitols. XV. The synthesis of 2-deoxystreptamine,,10.1016/s0040-4039(01)89972-x,1967-01-01,0.7240642786185283
Tetrahedron,The synthesis of ifflaiamine,,10.1016/s0040-4039(01)89839-7,1967-01-01,0.7240642786185283
Tetrahedron,Synthesis of kasuganobiosamine,,10.1016/s0040-4039(00)89735-x,1968-01-01,0.7240642786185283
Tetrahedron,Terpenoids XCII Synthesis of 1-oxoeudesmanes,,10.1016/s0040-4039(00)75718-2,1966-01-01,0.7240642786185283
Tetrahedron,Synthesis of hasubanan from morphinan,,10.1016/s0040-4039(01)84135-6,1966-01-01,0.7240642786185283
Tetrahedron,The synthesis of tricyclo[4.3.1.03'8]decane (isoadamantane) and solvolysis of its C3-carbinol,,10.1016/s0040-4039(01)99005-7,1968-01-01,0.7240642786185283
Tetrahedron,"Synthesis of a [1,2-]furo[5,6-]thienocycloöctatetraene and [1,2-]thienocycloöctatetraene",,10.1016/s0040-4039(00)75564-x,1968-01-01,0.7240642786185283
Tetrahedron,The synthesis of codeine and morphine glucuronides,,10.1016/s0040-4039(00)89585-4,1968-01-01,0.7240642786185283
Tetrahedron,Synthesis of illudins. I. Synthesis of the skeleton,,10.1016/s0040-4039(01)89698-2,1967-01-01,0.7240642786185283
Tetrahedron,The synthesis of 4β-hydroxychamaecynone and 4α-hydroxyisochamaecynone,,10.1016/s0040-4039(01)88784-0,1969-01-01,0.7240642786185283
Tetrahedron,The synthesis of bromosultones,,10.1016/s0040-4039(01)87773-x,1969-01-01,0.7240642786185283
Tetrahedron,Synthesis of (±)-isolongifolene,,10.1016/s0040-4039(00)90882-7,1967-01-01,0.7240642786185283
Tetrahedron,"The synthesis of 2,2-d2-cyclohexanone and 2,2-d2-cyclopentanone",,10.1016/s0040-4039(01)87883-7,1969-01-01,0.7240642786185283
Tetrahedron,"A synthesis of 1,6-dioxaspiro[4.5]dec-3-enes.",,10.1016/s0040-4039(00)95551-5,1987-01-01,0.7240642786185283
Tetrahedron,Synthesis of iminodipyrimidines,,10.1016/s0040-4039(01)87742-x,1969-01-01,0.7240642786185283
Tetrahedron,The synthesis of tetrahymanol,,10.1016/s0040-4039(00)90082-0,1965-01-01,0.7240642786185283
Synthesis,"Synthesis of 2,5-Diiodopyrazine by Deprotonative Dimetalation of Pyrazine",International audience,10.1055/s-0028-1083218,2008-11-06,0.7240642786185283
Tetrahedron,Synthesis of glycosyl dipyrromethanes,,10.1016/j.tetlet.2009.03.002,2009-03-07,0.7240642786185283
Tetrahedron,"Synthesis of 1,2,3,4-tetrahydroisoquinolines from α-methyldopa",,10.1016/s0040-4039(00)75398-6,1968-01-01,0.7240642786185283
Tetrahedron,"The synthesis of (1s, 2r, 4r, 5s, 6r)-1,2,4,5,6-penta--benzoylmyoinositol.",,10.1016/s0040-4039(01)99082-3,1968-01-01,0.7240642786185283
Tetrahedron,A synthesis of phytosphingosine from D-glucosamine,,10.1016/s0040-4039(00)77201-7,1965-01-01,0.7240642786185283
Tetrahedron,Synthesis of dl-tetrahydroeremophilone,,10.1016/s0040-4039(00)75524-9,1968-01-01,0.7240642786185283
Tetrahedron,"The synthesis of tricyclo[3.2.1.0 3,6 ]octan-7-one",,10.1016/s0040-4039(01)88472-0,1969-01-01,0.7240642786185283
Tetrahedron,Mono- and dithionopeptide synthesis,,10.1016/s0040-4039(00)96073-8,1987-01-01,0.7240642786185283
Tetrahedron,Synthesis of the glivocarcin-M aglycone,,10.1016/s0040-4039(00)96747-9,1987-01-01,0.7240642786185283
Tetrahedron,Synthesis of antimicrotubule dibenzoxepines,,10.1016/j.tetlet.2010.04.039,2010-04-17,0.7240642786185283
Tetrahedron,Synthesis of tyrocidine C,,10.1016/s0040-4039(01)97998-5,1970-01-01,0.7240642786185283
Tetrahedron,Synthesis of 5-thiabicyclo[2.1.1]hexane,,10.1016/s0040-4039(01)98376-5,1970-01-01,0.7240642786185283
Tetrahedron,Synthesis of the isoindolobenzazepine alkaloid lennoxamine,,10.1016/s0040-4039(00)96871-0,1987-01-01,0.7240642786185283
Tetrahedron,Synthesis of isoclovene,,10.1016/s0040-4039(00)96500-6,1987-01-01,0.7240642786185283
Tetrahedron,"‘Click’ synthesis of ferrocenyl-, biferrocenyl-, and cobalticenyl-triazolyl-β-cyclodextrins",,10.1016/j.tetlet.2010.06.115,2010-07-01,0.7240642786185283
Tetrahedron,A synthesis of d-diacetylmethylkasugaminide,,10.1016/s0040-4039(01)88589-0,1969-01-01,0.7240642786185283
Tetrahedron,Synthesis of dl-cepharanthine,,10.1016/s0040-4039(01)89985-8,1967-01-01,0.7240642786185283
Tetrahedron,A synthesis of pseudo-gloeosporone,,10.1016/s0040-4039(00)96375-5,1987-01-01,0.7240642786185283
Tetrahedron,Synthesis of proaporphine alkaloids. (±)-Hexahydropronuciferine,,10.1016/s0040-4039(01)88933-4,1969-01-01,0.7240642786185283
Tetrahedron,"Synthesis of 2,2-dimethylchromenes",,10.1016/s0040-4039(01)87888-6,1969-01-01,0.7240642786185283
Tetrahedron,On the synthesis of ajmaline,,10.1016/s0040-4039(01)97693-2,1969-01-01,0.7240642786185283
Tetrahedron,Sensitized photooxidation of thujopsene: Synthesis of thujopsadiene,,10.1016/s0040-4039(01)88356-8,1969-01-01,0.7240642786185283
Tetrahedron,A synthesis of dihydrocorynantheol and 3-epi-dihydrocorynantheol,,10.1016/s0040-4039(01)97749-4,1969-01-01,0.7240642786185283
Tetrahedron,Synthesis of septicine,,10.1016/s0040-4039(01)88607-x,1969-01-01,0.7240642786185283
Tetrahedron,The synthesis of 2- and 3-fluorokhellin,,10.1016/s0040-4039(01)83846-6,1987-01-01,0.7240642786185283
Tetrahedron,Isopavine alkaloids: Synthesis biosynthetic speculations,,10.1016/s0040-4039(01)87928-4,1969-01-01,0.7240642786185283
Tetrahedron,A synthesis of enol lactones,,10.1016/s0040-4039(01)88645-7,1969-01-01,0.7240642786185283
Tetrahedron,"Synthesis of lucernol and sativol, dimethylether",,10.1016/s0040-4039(00)90786-x,1967-01-01,0.7240642786185283
Tetrahedron,-azoxy aikanes. I. Synthesis,,10.1016/s0040-4039(01)88771-2,1969-01-01,0.7240642786185283
Tetrahedron,Chichibabin pyridinium synthesis,,10.1016/j.tetlet.2019.01.011,2019-01-08,0.7240642786185283
Tetrahedron,Synthesis of /-/corynantheidine,,10.1016/s0040-4039(01)98964-6,1968-01-01,0.7240642786185283
Tetrahedron,Azapentatriafulvalenium ions. i. synthesis,,10.1016/s0040-4039(00)75555-9,1968-01-01,0.7240642786185283
Tetrahedron,The synthesis of sanguinarine,,10.1016/s0040-4039(00)72370-7,1968-01-01,0.7240642786185283
Tetrahedron,The synthesis of dl-hernandine,,10.1016/s0040-4039(01)98717-9,1968-01-01,0.7240642786185283
Tetrahedron,Synthesis of carbadisaccharide mimics of galactofuranosides,,10.1016/j.tetlet.2009.06.115,2009-07-02,0.7240642786185283
Tetrahedron,Synthesis of aporphines,,10.1016/s0040-4039(00)90924-9,1967-01-01,0.7240642786185283
Tetrahedron,"Synthesis of a tricyclo[3.3.3.01,5]undecane system",,10.1016/s0040-4039(00)76131-4,1966-01-01,0.7240642786185283
Tetrahedron,Synthesis of tetrasubstituted pyrazines and pyrazine N-oxides,,10.1016/j.tetlet.2009.12.053,2009-12-17,0.7240642786185283
Tetrahedron,Synthesis of ferrocene annulated trifluoromethylated heterocycles with crispine and lamellarin skeletons,,10.1016/j.tetlet.2019.07.007,2019-07-05,0.7240642786185283
Synthesis,Synthesis of Two Naphthoquinone Antibiotics Pentalongin and Psychorubrin,,10.1055/s-1999-3613,1999-11-01,0.7240642786185283
Synthesis,The Synthesis of (E) and (Z)-Combretastatins A-4 and a Phenanthrene from Combretum caffrum,,10.1055/s-1999-3570,1999-09-01,0.7240642786185283
Tetrahedron,Synthesis of regiospecifically polysubstituted pyridazinones,,10.1016/j.tetlet.2007.09.013,2007-09-07,0.7240642786185283
Tetrahedron,Synthesis of eucomin and (±)eucomol,,10.1016/s0040-4039(00)72872-3,1968-01-01,0.7240642786185283
Tetrahedron,Synthesis of levantenolides from acyclic progenitor,,10.1016/s0040-4039(01)97996-1,1970-01-01,0.7240642786185283
Tetrahedron,"The tricyclo[5.2.0.02,5]nonane system: a synthesis of homocubanone",,10.1016/0040-4039(70)80061-2,1970-01-01,0.7240642786185283
Tetrahedron,The synthesis of enamides,,10.1016/s0040-4039(01)89055-9,1965-01-01,0.7240642786185283
Tetrahedron,Synthesis of (+)-striatene: confirmation of its stereostructure,,10.1016/j.tetlet.2009.07.138,2009-08-07,0.7240642786185283
Tetrahedron,"The synthesis of 6,7-dehydroquebrachamine",,10.1016/s0040-4039(01)98277-2,1970-01-01,0.7240642786185283
Tetrahedron,The synthesis of a methylenecyclopropene (triafulvene) by proton abstraction from a cyclopropenyl cation,,10.1016/s0040-4039(00)89983-9,1965-01-01,0.7240642786185283
Tetrahedron,Synthesis of helioxanthin,,10.1016/0040-4039(70)80025-9,1970-01-01,0.7240642786185283
Tetrahedron,A multicomponent synthesis of cyclopropanes,,10.1016/j.tetlet.2008.08.033,2008-08-30,0.7240642786185283
Tetrahedron,"Synthesis of 6-epicastanospermine and 1,6-diepicastanospermine from L-gulonolactone and synthesis of L-6-epicastanospermine and L-1,6-diepicastanospermine from D-gulonolactone",,10.1016/0040-4039(88)85305-x,1988-01-01,0.7240642786185283
Tetrahedron,A synthesis of (±)-otobain,,10.1016/s0040-4039(00)76261-7,1966-01-01,0.7240642786185283
Tetrahedron,Synthesis of theaspirone,,10.1016/s0040-4039(01)88016-3,1969-01-01,0.7240642786185283
Tetrahedron,Synthesis of illudol (1) protoilludane skeleton,,10.1016/s0040-4039(01)88545-2,1969-01-01,0.7240642786185283
Tetrahedron,Synthesis of dendrolasin,,10.1016/s0040-4039(01)87877-1,1969-01-01,0.7240642786185283
Tetrahedron,"The synthesis of actinidiolide, dihydroactinidiolide and actinidol",,10.1016/s0040-4039(00)75561-4,1968-01-01,0.7240642786185283
Tetrahedron,Synthesis of leonurine,,10.1016/s0040-4039(01)98821-5,1968-01-01,0.7240642786185283
Tetrahedron,"Synthesis of pyridazine 1,2-dioxides",,10.1016/s0040-4039(00)76380-5,1968-01-01,0.7240642786185283
Tetrahedron,"Synthesis of heptahelicene (1) benzo [c] phenanthro [4, 3-g ]phenanthrene.",,10.1016/s0040-4039(00)90586-0,1967-01-01,0.7240642786185283
Tetrahedron,"A synthesis of tricyclo[3.3.0.03,7]Octane (bisnoradamantane); solvolysis of its mono and dicarbinols",,10.1016/s0040-4039(01)99013-6,1968-01-01,0.7240642786185283
Tetrahedron,The synthesis of noradamantane,,10.1016/s0040-4039(00)90870-0,1967-01-01,0.7240642786185283
Tetrahedron,"Synthesis of (±)-desepoxy-4,5-didehydromethylenomycin A",,10.1016/0040-4039(81)80028-7,1981-01-01,0.7240642786185283
Tetrahedron,A regiospecific synthesis of (±)-decarbomethoxyaklavinone,,10.1016/s0040-4039(01)90437-x,1981-01-01,0.7240642786185283
Tetrahedron,Biomimetic synthesis of Cbz-(S)-dolaphenine,,10.1016/j.tetlet.2012.07.027,2012-07-16,0.7240642786185283
Tetrahedron,Synthesis of (±)warburganal,,10.1016/s0040-4039(01)91342-5,1981-01-01,0.7240642786185283
Tetrahedron,Synthesis of (±)-julandine and (±)-cryptopleurine,,10.1016/s0040-4039(01)90476-9,1981-01-01,0.7240642786185283
Tetrahedron,Synthesis of pyrimidinopurinophanes,,10.1016/s0040-4039(01)82076-1,1981-01-01,0.7240642786185283
Tetrahedron,"Synthesis of euryfuran, valdiviolide, and confertifolin",,10.1016/s0040-4039(01)83030-6,1981-01-01,0.7240642786185283
Tetrahedron,Indoloquinolizidine synthesis,,10.1016/s0040-4039(00)87140-3,1982-01-01,0.7240642786185283
Tetrahedron,"A synthesis of the tricyclo[6.3.0.02,6]undecane system.",,10.1016/s0040-4039(00)85874-8,1982-01-01,0.7240642786185283
Tetrahedron,"Synthesis of 2-azabicyclo[3.3.1]nonan-3,7-diones and their fischer indolization",,10.1016/s0040-4039(01)80673-0,1989-01-01,0.7240642786185283
Tetrahedron,A biomimetic synthesis of Δ1-tetrahydrocannabinol,,10.1016/s0040-4039(00)87498-5,1982-01-01,0.7240642786185283
Tetrahedron,"Synthesis of 6S, 7S-anhydro-serricornine.",,10.1016/s0040-4039(00)87646-7,1982-01-01,0.7240642786185283
Tetrahedron,"Synthesis of 3-carbomethoxy-3,4-dialkylcyclohexanones",,10.1016/s0040-4039(00)87594-2,1982-01-01,0.7240642786185283
Tetrahedron,An informal synthesis of ± lysergine,,10.1016/s0040-4039(00)86808-2,1982-01-01,0.7240642786185283
Tetrahedron,"Synthesis of the coumarin, hortiolone",,10.1016/s0040-4039(00)85729-9,1982-01-01,0.7240642786185283
Tetrahedron,"Hashish: Synthesis of d1-δ1,6--tetrahydrocannabinol (THC)",,10.1016/s0040-4039(00)91126-2,1975-01-01,0.7240642786185283
Tetrahedron,"Synthesis of a cyclohexadepsipeptide, protodestruxin",,10.1016/s0040-4039(00)72010-7,1975-01-01,0.7240642786185283
Tetrahedron,Synthesis of wilsoniamines A and B,,10.1016/j.tetlet.2013.03.122,2013-04-08,0.7240642786185283
Tetrahedron,Smiles rearrangements in the synthesis of hexachlorodibenzo-p-dioxins,,10.1016/s0040-4039(00)75019-2,1975-01-01,0.7240642786185283
Tetrahedron,Synthesis of 1-azidocyclopropanecarboxylates from 2-azido-2alkenoates,,10.1016/s0040-4039(00)87272-x,1982-01-01,0.7240642786185283
Tetrahedron,Synthesis of some [n.1.3.1]- and [n.1.2.1] paddlanes,,10.1016/0040-4039(81)80103-7,1981-01-01,0.7240642786185283
Tetrahedron,Synthesis and spectra of paracyclophane dienes,,10.1016/s0040-4039(00)78029-4,1976-04-01,0.7240642786185283
Tetrahedron,"Synthesis of the coumarins, avicennol, dipetaline and dipetalolactone",,10.1016/s0040-4039(00)77976-7,1976-03-01,0.7240642786185283
Tetrahedron,Synthesis of polyfunctional triethoxysilanes by ‘click silylation’,,10.1016/j.tetlet.2013.12.037,2013-12-19,0.7240642786185283
Tetrahedron,A synthesis of β-2′-deoxyshowdomycin,,10.1016/s0040-4039(01)92522-5,1981-01-01,0.7240642786185283
Tetrahedron,Regiospecific synthesis of (±)-deoxyanthracyclinones,,10.1016/0040-4039(81)80003-2,1981-01-01,0.7240642786185283
Tetrahedron,Synthesis of oxa and dithiazepine azetidinones,,10.1016/s0040-4039(01)81996-1,1981-01-01,0.7240642786185283
Tetrahedron,Synthesis of 3-methylcholanthrene,,10.1016/s0040-4039(01)90245-x,1981-01-01,0.7240642786185283
Tetrahedron,"The synthesis of vafzelin and syncarpin, constitutents of",,10.1016/s0040-4039(01)81906-7,1981-01-01,0.7240642786185283
Tetrahedron,A synthesis of (±)-brefeldin A,,10.1016/s0040-4039(01)92968-5,1981-01-01,0.7240642786185283
Tetrahedron,"Synthesis of 1,3-ditellurole and ditellurolylium cations",,10.1016/s0040-4039(00)87150-6,1982-01-01,0.7240642786185283
Tetrahedron,Synthesis of mesoionic xanthine nucleosides,,10.1016/s0040-4039(01)90543-x,1981-01-01,0.7240642786185283
Tetrahedron,Synthesis of a secofuranoeremophilane from euryops hebecarpus [1],,10.1016/0040-4039(81)80157-8,1981-01-01,0.7240642786185283
Synlett,The First Synthesis of (±)-Taxodone,,10.1055/s-1994-22844,1994-01-01,0.7240642786185283
Tetrahedron,Synthesis of 4-ylidenebutenolides from 2-trimethylsiloxyfuran,,10.1016/s0040-4039(01)82929-4,1981-01-01,0.7240642786185283
Tetrahedron,Synthesis of polysaccharides. Glucorhamnan,,10.1016/0040-4039(81)80091-3,1981-01-01,0.7240642786185283
Tetrahedron,"Synthesis of 2- and 4-imino(1,2-a)pyridopyrimidines from allenic nitriles and 2-aminopyridines",,10.1016/s0040-4039(01)82083-9,1981-01-01,0.7240642786185283
Tetrahedron,Synthesis of conjugated triene-diamines through the isomerization of αω-diaminononadiynes,,10.1016/s0040-4039(01)92880-1,1981-01-01,0.7240642786185283
Tetrahedron,Synthesis of pyrenocine A and B,,10.1016/s0040-4039(01)82049-9,1981-01-01,0.7240642786185283
Tetrahedron,The synthesis of quinone methides from p-quinol benzoates,,10.1016/s0040-4039(01)92357-3,1981-01-01,0.7240642786185283
Tetrahedron,Synthesis of hastatoside tetraacetate,,10.1016/s0040-4039(00)91453-9,1975-01-01,0.7240642786185283
Tetrahedron,Synthesis of 5-hydroxyquinolines,,10.1016/j.tetlet.2010.05.058,2010-05-22,0.7240642786185283
Tetrahedron,Synthesis of (±)-linalool and (±)-hydroxylinalool from isoprene,,10.1016/s0040-4039(00)75057-x,1975-01-01,0.7240642786185283
Tetrahedron,Synthesis of the monoazabiphenylenes,,10.1016/s0040-4039(00)71923-x,1975-01-01,0.7240642786185283
Tetrahedron,Aminoglycoside antibiotics: synthesis of 6-0-(β-D-ribofuranosyl) paromamine,,10.1016/s0040-4039(01)92071-4,1974-01-01,0.7240642786185283
Tetrahedron,A vinylog of--xylylene. Synthesis of [2.6]paracyclophane,,10.1016/s0040-4039(01)91869-6,1974-01-01,0.7240642786185283
Tetrahedron,The synthesis of prostaglandin endoperoxide analogs,,10.1016/s0040-4039(00)72333-1,1975-01-01,0.7240642786185283
Tetrahedron,A biogenetically patterned synthesis of ()-eusiderin,,10.1016/s0040-4039(00)91340-6,1975-01-01,0.7240642786185283
Tetrahedron,Synthesis of a bicyclobutane-bridged α-diketone,,10.1016/s0040-4039(00)72184-8,1975-01-01,0.7240642786185283
Tetrahedron,Synthesis of partially hydrogenated oxa[5] and oxa[6]helicenes from β-chlorovinylaldehydes,,10.1016/j.tetlet.2013.06.101,2013-06-29,0.7240642786185283
Tetrahedron,"Synthesis of cyclohepta-4,6-diene-1,2,3-trione, o-tropoquinone",,10.1016/s0040-4039(00)72060-0,1975-01-01,0.7240642786185283
Tetrahedron,"The synthesis of 1,3-diamidophospholipids",,10.1016/j.tetlet.2010.07.140,2010-08-08,0.7240642786185283
Tetrahedron,Synthesis of fluorodeoxyscylloinositol and phosphatidylfluorodeoxyscylloinositol,,10.1016/s0040-4039(00)85882-7,1982-01-01,0.7240642786185283
Tetrahedron,The synthesis of azabicyclic heterocycles,,10.1016/j.tetlet.2010.03.123,2010-04-07,0.7240642786185283
Tetrahedron,Synthesis of arcyriaflavin B,,10.1016/s0040-4039(00)81677-9,1983-01-01,0.7240642786185283
Tetrahedron,"A synthesis of (S,S)-(+)-grahamimycin A1",,10.1016/s0040-4039(00)81387-8,1983-01-01,0.7240642786185283
Tetrahedron,An enantiodivergent formal synthesis of paecilomycine A,,10.1016/j.tetlet.2011.12.015,2011-12-09,0.7240642786185283
Tetrahedron,Enamine synthesis of 4-ketoaldehydes,,10.1016/s0040-4039(01)91876-3,1974-01-01,0.7240642786185283
Tetrahedron,The serendipitous synthesis of an oxabicyclo [3.2.0] heptadiene,,10.1016/s0040-4039(00)87607-8,1982-01-01,0.7240642786185283
Tetrahedron,The synthesis of rishitin,,10.1016/s0040-4039(00)91135-3,1975-01-01,0.7240642786185283
Tetrahedron,The synthesis of n-benzoylristosamine,,10.1016/s0040-4039(00)72071-5,1975-01-01,0.7240642786185283
Tetrahedron,Synthesis of ketomethylene analogs of dipeptides,,10.1016/s0040-4039(00)87388-8,1982-01-01,0.7240642786185283
Tetrahedron,Synthesis of(±)-descarboxylquadrone,,10.1016/s0040-4039(00)87176-2,1982-01-01,0.7240642786185283
Tetrahedron,"Synthesis of 9-azabicyclononanes from (z,z)-cycloocta-1,5-diene 1",,10.1016/s0040-4039(00)87667-4,1982-01-01,0.7240642786185283
Tetrahedron,Biomimetic synthesis of (±) panacene,,10.1016/s0040-4039(00)87525-5,1982-01-01,0.7240642786185283
Tetrahedron,Synthesis of aryltrifluoromethylacetylenes,,10.1016/s0040-4039(00)86826-4,1982-01-01,0.7240642786185283
Tetrahedron,Synthesis of conjugated nitroalkenes via nitroselenenylation of alkenes,,10.1016/s0040-4039(00)85699-3,1982-01-01,0.7240642786185283
Tetrahedron,A synthesis of 2-methyleneindane,,10.1016/s0040-4039(00)87306-2,1982-01-01,0.7240642786185283
Tetrahedron,A formal synthesis of (+)-lactacystin from 4-hydroxyproline,,10.1016/j.tetlet.2012.10.076,2012-10-26,0.7240642786185283
Tetrahedron,The synthesis of dendropanoxide from friedelin,,10.1016/s0040-4039(00)75101-x,1975-01-01,0.7240642786185283
Tetrahedron,Synthesis of 1-isocyano sugars,,10.1016/s0040-4039(00)93062-4,1976-09-01,0.7240642786185283
Tetrahedron,Synthesis of colletochlorin D,,10.1016/s0040-4039(00)85655-5,1982-01-01,0.7240642786185283
Tetrahedron,Synthesis of farinomalein,,10.1016/j.tetlet.2010.01.083,2010-02-02,0.7240642786185283
Tetrahedron,Synthesis of azidochloromethane and azidobromomethane,,10.1016/j.tetlet.2010.03.094,2010-03-30,0.7240642786185283
Tetrahedron,A synthesis of 3α-dihydrocadambine,,10.1016/s0040-4039(00)87341-4,1982-01-01,0.7240642786185283
Tetrahedron,"Synthesis of macrolide antibiotics. 2. Synthesis of the C9-C13 segments of erythronolides A, B and oleandonolide",,10.1016/s0040-4039(01)82945-2,1981-01-01,0.7240642786185283
Tetrahedron,"Photo-oxygenation of 2,3-homotropone and synthesis of 1,2-dioxocycloocta-3,5-diene from the epidioxide",,10.1016/s0040-4039(00)71832-6,1975-01-01,0.7240642786185283
Tetrahedron,"1,4,5,8,9-pentamethylanthracene. Synthesis and protonation",,10.1016/s0040-4039(00)91040-2,1975-01-01,0.7240642786185283
Tetrahedron,Dihydropyrene annelated with dihydrothieno[3.4-b]pyrazine: synthesis and photoswitching property,,10.1016/j.tetlet.2010.05.092,2010-05-26,0.7240642786185283
Tetrahedron,Synthesis of cepharadione B,,10.1016/s0040-4039(00)77921-4,1976-02-01,0.7240642786185283
Tetrahedron,Dilithiated N-allylcarboxamides. A synthesis of enamides,,10.1016/s0040-4039(00)70532-6,1978-01-01,0.7240642786185283
Tetrahedron,Synthesis of prostaglandin I3 (PGI3),,10.1016/s0040-4039(01)94778-1,1978-01-01,0.7240642786185283
Tetrahedron,Synthesis of 9(O)-thiaprostacyclin,,10.1016/s0040-4039(01)85331-4,1978-01-01,0.7240642786185283
Tetrahedron,Synthesis of oxygenated 4-arylisoflavans and 4-arylflavans,,10.1016/j.tetlet.2012.09.117,2012-10-02,0.7240642786185283
Synthesis,Titanium and Zirconium in Orgnanic Synthesis,,10.1055/s-2003-39387,2003-01-01,0.7240642786185283
Tetrahedron,Stereocontrolled synthesis of showdomycin and 6-azapseudouridines,,10.1016/s0040-4039(01)94682-9,1978-01-01,0.7240642786185283
Tetrahedron,Synthesis of saturated and unsaturated dithioesters,,10.1016/s0040-4039(01)91584-9,1978-01-01,0.7240642786185283
Tetrahedron,"Towards polyazaazulenes. The synthesis of 3,7-dihydropyrrolo [3,4-d] [1,2] diazepines",,10.1016/s0040-4039(01)95149-4,1978-01-01,0.7240642786185283
Tetrahedron,The synthesis of ruscodibenzofuran,,10.1016/s0040-4039(01)85853-6,1978-01-01,0.7240642786185283
Tetrahedron,Biomimetic synthesis of leukotriene A,,10.1016/s0040-4039(01)81927-4,1981-01-01,0.7240642786185283
Tetrahedron,Stereoconservative synthesis of dihydromeroquinene (cincholoipon) from secologanin.,,10.1016/s0040-4039(01)94617-9,1978-01-01,0.7240642786185283
Tetrahedron,Synthesis of lupinifolin,,10.1016/s0040-4039(01)94741-0,1978-01-01,0.7240642786185283
Tetrahedron,Electroreductive synthesis of olefins from β-hydroxysulfides,,10.1016/s0040-4039(01)94868-3,1978-01-01,0.7240642786185283
Tetrahedron,"Synthesis of the isoquinoline alkaloid, crispine C",,10.1016/j.tetlet.2012.05.113,2012-05-30,0.7240642786185283
Tetrahedron,Synthesis and spectra of pyrylo-trimethinecyanines,,10.1016/s0040-4039(01)85342-9,1978-01-01,0.7240642786185283
Tetrahedron,"Synthesis of 1,5-diazacyclooctanes from 2,4,6,8-tetraketo-1,5-diazabicyclo[3,3,0]octanes",,10.1016/s0040-4039(01)85327-2,1978-01-01,0.7240642786185283
Tetrahedron,Synthesis of ent-ambrox® from (−)-nidorellol,,10.1016/j.tetlet.2012.07.120,2012-08-03,0.7240642786185283
Tetrahedron,Synthesis of (+)-pachydictyol-A,,10.1016/s0040-4039(01)85416-2,1978-01-01,0.7240642786185283
Tetrahedron,"B-sulfinyl enones, synthons for terpenoid synthesis",,10.1016/s0040-4039(01)85383-1,1978-01-01,0.7240642786185283
Tetrahedron,"Stereo- and regiospecific synthesis of unbranched alkenes and 1,4-alkadienes by meams of stabilised organocuprates",,10.1016/s0040-4039(01)91580-1,1978-01-01,0.7240642786185283
Tetrahedron,"Synthesis of 2,6-diaryl-1,2-dihydropyridines through a 6π-electrocyclization of N-sulfonylazatrienes",,10.1016/j.tetlet.2014.10.034,2014-10-13,0.7240642786185283
Tetrahedron,Synthesis of caprazamycin B,,10.1016/j.tetlet.2015.04.065,2015-04-20,0.7240642786185283
Tetrahedron,Synthesis of scalaridine A,,10.1016/j.tetlet.2015.09.033,2015-09-13,0.7240642786185283
Tetrahedron,Synthesis of π-extended platinum porphyrins,,10.1016/j.tetlet.2015.11.018,2015-11-08,0.7240642786185283
Tetrahedron,First synthesis of (±)-hostasolide A,,10.1016/j.tetlet.2015.09.009,2015-09-05,0.7240642786185283
Tetrahedron,Synthesis of β-triphosphotriester pronucleotides,,10.1016/j.tetlet.2015.03.036,2015-03-16,0.7240642786185283
Tetrahedron,Synthesis and enantioseparation of atropisomers of serotonin dimer,,10.1016/j.tetlet.2015.04.127,2015-05-11,0.7240642786185283
Tetrahedron,Synthesis of tunichrome Sp-1,,10.1016/j.tetlet.2015.08.047,2015-08-21,0.7240642786185283
Synthesis,"The Synthesis of 1,2,3-Triazoles from Nitroalkenes - Revisited",International audience,10.1055/s-2005-918463,2005-01-01,0.7240642786185283
Tetrahedron,Biomimetic synthesis of diversifolin,,10.1016/j.tetlet.2012.11.134,2012-12-05,0.7240642786185283
Tetrahedron,Formal synthesis of (+)-crocacin C,,10.1016/j.tetlet.2012.02.049,2012-02-18,0.7240642786185283
Tetrahedron,Formal synthesis of (+)-gliocladin C,,10.1016/j.tetlet.2012.12.007,2012-12-12,0.7240642786185283
Tetrahedron,Synthesis of the C22–C37 segment of prorocentin,,10.1016/j.tetlet.2011.01.042,2011-01-19,0.7240642786185283
Tetrahedron,A synthesis of tabersonine,,10.1016/s0040-4039(01)94609-x,1978-01-01,0.7240642786185283
Tetrahedron,Synthesis of benzo[c]phenanthrene dihydrodiols,,10.1016/s0040-4039(01)86432-7,1979-01-01,0.7240642786185283
Tetrahedron,Formal synthesis of soybean phytoalexin glyceollin I,,10.1016/j.tetlet.2014.01.142,2014-02-05,0.7240642786185283
Tetrahedron,Synthesis of the C38–C54 spiroketal segment of halichondrin B,,10.1016/j.tetlet.2012.02.090,2012-03-07,0.7240642786185283
Tetrahedron,First synthesis of P-chirogenic prophosphatranes,,10.1016/j.tetlet.2011.01.041,2011-01-19,0.7240642786185283
Tetrahedron,"Synthesis of sidisterone, a phytoecdysteroid from Silene dioica (L.) Clairv.",,10.1016/j.tetlet.2011.07.139,2011-08-08,0.7240642786185283
Synthesis,Synthesis of Biaryls,,10.1055/s-2005-872047,2005-01-01,0.7240642786185283
Tetrahedron,Synthesis of 3-iodothiophenes via iodocyclization of (Z)-thiobutenynes,,10.1016/j.tetlet.2013.10.118,2013-10-31,0.7240642786185283
Tetrahedron,Synthesis of the diols and diolepoxides of carcinogenic hydrocarbons,,10.1016/s0040-4039(01)83679-0,1977-01-01,0.7240642786185283
Tetrahedron,"Synthesis of O,S-thioacetals of formylphosphonates",,10.1016/s0040-4039(00)77887-7,1976-02-01,0.7240642786185283
Tetrahedron,"Synthesis of [2.0.2.0]metacyclophanediene and bi-4,5-phenanthrylene",,10.1016/s0040-4039(01)92794-7,1977-01-01,0.7240642786185283
Tetrahedron,Synthesis of N-benzoyl--daunosamine from -threonine,,10.1016/s0040-4039(01)82053-0,1981-01-01,0.7240642786185283
Tetrahedron,"Synthesis and photochemistry of 2,3,8,9-tetrahydroindenone-1",,10.1016/s0040-4039(01)83941-1,1980-01-01,0.7240642786185283
Tetrahedron,Synthesis of furo[b]tropylium tetrafluoroborate,,10.1016/s0040-4039(00)78692-8,1980-01-01,0.7240642786185283
Tetrahedron,Synthesis of o-halogenophenylacetylenes via the dianion of phenylacetylene (1),,10.1016/s0040-4039(01)92942-9,1981-01-01,0.7240642786185283
Tetrahedron,Synthesis of thromboxane B2,,10.1016/s0040-4039(00)93901-7,1976-09-01,0.7240642786185283
Tetrahedron,Expeditious synthesis of fluorinated styrylbenzenes and polyaromatic hydrocarbons,,10.1016/j.tetlet.2012.11.022,2012-11-21,0.7240642786185283
Tetrahedron,Biomimetic synthesis of trichotomine,,10.1016/s0040-4039(01)92806-0,1977-01-01,0.7240642786185283
Tetrahedron,Synthesis of the carbocyclic analog of enterobactin,,10.1016/s0040-4039(01)83391-8,1977-01-01,0.7240642786185283
Tetrahedron,Synthesis of cytotoxic spermidine metabolites from the soft coral,,10.1016/s0040-4039(00)92817-x,1980-01-01,0.7240642786185283
Tetrahedron,Synthesis of (±)-negamycin and of (±)-epinegamycin,,10.1016/s0040-4039(00)77742-2,1980-01-01,0.7240642786185283
Tetrahedron,Synthesis of (±)-lecanindole D,,10.1016/j.tetlet.2013.06.084,2013-06-26,0.7240642786185283
Tetrahedron,Unsymmetrical diene-nitrone cycloadditions. A synthesis of the quinolizidine nucleus.,,10.1016/s0040-4039(01)94852-x,1978-01-01,0.7240642786185283
Tetrahedron,"Benzologs of allopurinol: Synthesis of pyrazolo [4,3-g] and [3,4-f] quinazolinones",,10.1016/s0040-4039(00)77398-9,1980-01-01,0.7240642786185283
Tetrahedron,"Synthesis of 7-trifluoromethylpyrazolo[1,5-a]pyridinedicarboxylate",,10.1016/j.tetlet.2012.09.136,2012-10-13,0.7240642786185283
Tetrahedron,"Synthesis of (2Z,6Z,10Z,14E,18E)-farnesylfarnesol,",,10.1016/s0040-4039(01)81892-x,1981-01-01,0.7240642786185283
Tetrahedron,"The synthesis of norsurfactin, a hemolytic, anticoagulant cyclodepsipeptide",,10.1016/s0040-4039(00)93779-1,1976-05-01,0.7240642786185283
Tetrahedron,Cyanoketenes. Synthesis and cycloadditions to formimidates,,10.1016/s0040-4039(01)85417-4,1978-01-01,0.7240642786185283
Tetrahedron,"Synthesis of dihydrobenzoimidazo[2,1-a]isoquinolines",,10.1016/j.tetlet.2012.05.132,2012-06-01,0.7240642786185283
Tetrahedron,Synthesis and cycloadditions of a bicyclobutane bridged diazoketone,,10.1016/s0040-4039(01)94762-8,1978-01-01,0.7240642786185283
Tetrahedron,Stereocontrolled synthesis of 8-iso-prostaglandin E1 and E2,,10.1016/s0040-4039(01)94601-5,1978-01-01,0.7240642786185283
Tetrahedron,Synthesis of triostin A,,10.1016/s0040-4039(01)94619-2,1978-01-01,0.7240642786185283
Tetrahedron,Synthesis of paragloboside analogs,,10.1016/0040-4039(78)80025-2,1978-01-01,0.7240642786185283
Tetrahedron,Synthesis of isomeric corniculatolides,,10.1016/j.tetlet.2012.09.010,2012-09-20,0.7240642786185283
Tetrahedron,The synthesis of 4-demethoxydahnomycin,,10.1016/s0040-4039(01)95251-7,1978-01-01,0.7240642786185283
Tetrahedron,Synthesis of 6′-aminomethyltripyrranes of biosynthetic interest,,10.1016/s0040-4039(00)93725-0,1976-01-01,0.7240642786185283
Tetrahedron,The synthesis of locust adipokinetic hormone,,10.1016/s0040-4039(01)83721-7,1977-01-01,0.7240642786185283
Tetrahedron,Synthesis of (+)-(6:1′)-pestalotin and (+)-(1′)-epipestalotin,,10.1016/s0040-4039(00)93871-1,1976-09-01,0.7240642786185283
Tetrahedron,Synthesis of S-deoxo- (R) -sparsomycin,,10.1016/s0040-4039(00)92958-7,1976-05-01,0.7240642786185283
Tetrahedron,Synthesis of -difluorosaccharides,,10.1016/s0040-4039(01)83259-7,1977-01-01,0.7240642786185283
Tetrahedron,Synthesis of perfluoro-2-alkynenitriles,,10.1016/s0040-4039(01)92481-5,1981-01-01,0.7240642786185283
Tetrahedron,Synthesis of cytotoxic spermidine metabolites from the soft coral,,10.1016/0040-4039(80)80223-1,1980-01-01,0.7240642786185283
Tetrahedron,"The synthesis of trisnorcybrodolide, A metabolite of brodie.",,10.1016/s0040-4039(00)93644-x,1980-01-01,0.7240642786185283
Tetrahedron,Synthesis of 5-ethynylcytosine and 5-ethynylcytidine,,10.1016/s0040-4039(01)83793-x,1977-01-01,0.7240642786185283
Tetrahedron,"Sensitized Photooxygenation of β,β-dimethylstyrenes; synthesis of (±)-crotepoxide",,10.1016/s0040-4039(01)83239-1,1977-01-01,0.7240642786185283
Tetrahedron,"Synthesis of dihydrodiols from chrysene and dibenzo[a,h]anthracene",,10.1016/s0040-4039(01)83415-8,1977-01-01,0.7240642786185283
Tetrahedron,"The synthesis and the antiaromatic character of dibenz[,,1]azapentalenes",,10.1016/s0040-4039(00)92913-7,1976-05-01,0.7240642786185283
Tetrahedron,Synthesis of 1-chlorophosphirenes in the coordination sphere of tungsten,,10.1016/s0040-4039(00)98760-4,1985-01-01,0.7240642786185283
Organic Letters,Synthesis of (â)-Oxycodone,,,2014-01-01,0.7240642786185283
Tetrahedron,Synthesis of spin-labeled analogs of dihydroxyaminoalkylaminoanthraquinone,,10.1016/s0040-4039(00)99858-7,1984-01-01,0.7240642786185283
Tetrahedron,Synthesis of bostrycoidin and 8-0-methylbostrycoidin,,10.1016/s0040-4039(00)71142-7,1980-01-01,0.7240642786185283
Tetrahedron,Synthesis of macrolide antibiotics. 3. Revised synthesis of C9- C13 segment of erythronolide A.,,10.1016/s0040-4039(01)90023-1,1984-01-01,0.7240642786185283
Tetrahedron,Synthesis of polynaphthoquinone,,10.1016/s0040-4039(01)91099-8,1984-01-01,0.7240642786185283
Tetrahedron,Synthesis of silylcyclopropanes via arsonium ylides,,10.1016/s0040-4039(01)81456-8,1984-01-01,0.7240642786185283
Tetrahedron,Synthesis of N4-acylspermidines,,10.1016/s0040-4039(01)91005-6,1984-01-01,0.7240642786185283
Tetrahedron,Synthesis of ellipticine,,10.1016/s0040-4039(01)81172-2,1984-01-01,0.7240642786185283
Tetrahedron,Synthesis de carbodiimides par photoaddition de nitrenes sur les isonitriles,,10.1016/s0040-4039(00)87164-6,1982-01-01,0.7240642786185283
Tetrahedron,"Synthesis of 1,2′-biadamantane",,10.1016/s0040-4039(01)97439-8,1971-01-01,0.7240642786185283
Tetrahedron,"β-lactams from azetidine carboxylates. A synthesis of (-3-ana, the nucleus of the nocardicins",,10.1016/s0040-4039(01)87199-9,1979-01-01,0.7240642786185283
Synlett,"Synthesis of Sugar 2,4-Diketoesters",,10.1055/s-1991-20845,1991-01-01,0.7240642786185283
Tetrahedron,The first synthesis of PEG–carotenoid conjugates,,10.1016/j.tetlet.2011.04.039,2011-04-19,0.7240642786185283
Tetrahedron,"First synthesis of 4-aminopyrido[2′,3′:4,5]furo[3,2-d]pyrimidines",,10.1016/j.tetlet.2011.12.042,2011-12-16,0.7240642786185283
Tetrahedron,An expeditious synthesis of quercetin 3-O-β-d-glucuronide from rutin,,10.1016/j.tetlet.2011.06.108,2011-07-05,0.7240642786185283
Synlett,First Synthesis of Theonellin Isocyanide,,10.1055/s-1991-20849,1991-01-01,0.7240642786185283
Tetrahedron,Synthesis of the insecticidal 1′-acetoxy-mammeins and surangin b,,10.1016/s0040-4039(00)98875-0,1985-01-01,0.7240642786185283
Tetrahedron,An enantiospecific synthesis of estrone,,10.1016/s0040-4039(00)94746-4,1985-01-01,0.7240642786185283
Tetrahedron,Synthesis of 4-azepanones and heteroaromatic-fused azepines,,10.1016/j.tetlet.2011.11.129,2011-12-07,0.7240642786185283
Tetrahedron,Synthesis of [6-3H]--acetylmuramyl--alanyl--isoglutamine,,10.1016/s0040-4039(01)85952-9,1979-01-01,0.7240642786185283
Tetrahedron,A stereocontrolled synthesis of (−)-bestatin from an acyclic allylamine by iodocyclocarbamation,,10.1016/s0040-4039(01)91124-4,1984-01-01,0.7240642786185283
Tetrahedron,Synthesis of N-mono-alkylporphyrins,,10.1016/s0040-4039(01)81757-3,1984-01-01,0.7240642786185283
Tetrahedron,"Synthesis of homo-dinordrin, allenyl A-nor and dinor-steroids",,10.1016/s0040-4039(01)93581-6,1979-01-01,0.7240642786185283
Tetrahedron,Synthesis of a halogenated clavulone analog,,10.1016/s0040-4039(01)80851-0,1985-01-01,0.7240642786185283
Tetrahedron,Synthesis of 1-perfluoroalkynyl phosphonates,,10.1016/s0040-4039(00)98884-1,1985-01-01,0.7240642786185283
Tetrahedron,Synthesis of Necatorone,,10.1016/s0040-4039(00)98275-3,1985-01-01,0.7240642786185283
Tetrahedron,Synthesis of orellanine the lethal poison of a toadstool,,10.1016/s0040-4039(00)94981-5,1985-01-01,0.7240642786185283
Tetrahedron,"Synthesis of uvaretin, an antitumour and antimicrobial flavonoid",,10.1016/s0040-4039(00)94957-8,1985-01-01,0.7240642786185283
Tetrahedron,Synthesis of helminthogermacrene and β-elemene,,10.1016/s0040-4039(00)98953-6,1985-01-01,0.7240642786185283
Tetrahedron,Synthesis of difluoromethylene-prostaglandins,,10.1016/s0040-4039(01)95929-5,1973-01-01,0.7240642786185283
Tetrahedron,Synthesis of sequirosefuran,,10.1016/s0040-4039(01)87656-5,1973-01-01,0.7240642786185283
Tetrahedron,Concerning the synthesis of bufalin,,10.1016/s0040-4039(01)95706-5,1973-01-01,0.7240642786185283
Tetrahedron,"Synthesis of the coumarin, glabralactone",,10.1016/s0040-4039(01)84796-1,1972-01-01,0.7240642786185283
Tetrahedron,The synthesis of berberastine,,10.1016/s0040-4039(01)85200-x,1972-01-01,0.7240642786185283
Tetrahedron,"Synthesis of the coumarin, toddaculin",,10.1016/s0040-4039(01)84275-1,1972-01-01,0.7240642786185283
Tetrahedron,A synthesis of (±)-cryptojaponol and (±)-taxodione,,10.1016/s0040-4039(01)86325-5,1979-01-01,0.7240642786185283
Tetrahedron,Biomimetic synthesis of neodihydrothebaine and bractazonine from thebaine,,10.1016/s0040-4039(01)90210-2,1984-01-01,0.7240642786185283
Tetrahedron,Macrocyclic paracyclophane synthesis,,10.1016/s0040-4039(01)81606-3,1984-01-01,0.7240642786185283
Tetrahedron,On the synthesis of α-phenyltosyldiazomethane,,10.1016/s0040-4039(01)87665-6,1973-01-01,0.7240642786185283
Tetrahedron,Pyrromethane (dipyrrylmethane) and tripyrrane synthesis,,10.1016/s0040-4039(01)84806-1,1972-01-01,0.7240642786185283
Tetrahedron,The synthesis of 2-azasteroids,,10.1016/s0040-4039(01)94012-2,1972-01-01,0.7240642786185283
Tetrahedron,Synthesis of a steroidal cyclopropanol,,10.1016/s0040-4039(01)97333-2,1971-01-01,0.7240642786185283
Tetrahedron,Synthesis of 4-nitrocyclopenta[cd]pyrene,,10.1016/s0040-4039(00)94961-x,1985-01-01,0.7240642786185283
European Journal of Organic Chemistry,"NOTE OF THE SYNTHESIS OF 3,7-DICYANO-1,5-DIMETHYLSEMIBULLVALENE",,,1992-03-01,0.7240642786185283
Tetrahedron,A convinient synthesis of δ1-pyrolines and δ1-piperideines,,10.1016/s0040-4039(00)98976-7,1985-01-01,0.7240642786185283
Tetrahedron,Stereocontrolled synthesis of dihydropseudoclovene-B,,10.1016/s0040-4039(00)89308-9,1985-01-01,0.7240642786185283
Tetrahedron,The synthesis of thialeukotriene a4,,10.1016/s0040-4039(00)89272-2,1985-01-01,0.7240642786185283
Tetrahedron,"Synthesis of 2,3- and 2,7-dihydrothiepines",,10.1016/s0040-4039(01)93980-2,1972-01-01,0.7240642786185283
Tetrahedron,Synthesis of pukeleimide a,,10.1016/s0040-4039(00)89205-9,1985-01-01,0.7240642786185283
Tetrahedron,"Stereocontrolled (, and , ) synthesis of ⊙-hydroxyallylic sulphides",,10.1016/s0040-4039(01)80927-8,1985-01-01,0.7240642786185283
Tetrahedron,"Synthesis of (Z)-stilbendiol dibenzoate by sensitized photooxygenation of 2,3,5,6-tetraphenyl-p-dioxin",,10.1016/s0040-4039(00)98741-0,1985-01-01,0.7240642786185283
Tetrahedron,Stereocontrolled Synthesis of Petrosterol,,10.1016/s0040-4039(00)98161-9,1985-01-01,0.7240642786185283
Tetrahedron,Synthesis of the naphthacenequinone SS-228R,,10.1016/s0040-4039(00)89278-3,1985-01-01,0.7240642786185283
Tetrahedron,"Synthesis of (±)-8,9-deoxyalliacol B",,10.1016/s0040-4039(00)61919-6,1985-01-01,0.7240642786185283
Tetrahedron,Synthesis of d-erythro-sphingosines,,10.1016/s0040-4039(00)85510-0,1986-01-01,0.7240642786185283
Tetrahedron,"Synthesis of 2R,3S,4R-dihydroxyproline from D-ribonolactone",,10.1016/s0040-4039(00)84754-1,1986-01-01,0.7240642786185283
Tetrahedron,Synthesis of deoxyisopodophyllotoxin and epiisopodophyllotoxin.,,10.1016/s0040-4039(01)84603-7,1985-01-01,0.7240642786185283
Tetrahedron,Synthesis of anhydrolycorine and dimethylapoerysopine,,10.1016/s0040-4039(01)85161-3,1972-01-01,0.7240642786185283
Tetrahedron,Synthesis of organotellurium acetates,,10.1016/s0040-4039(01)94425-9,1972-01-01,0.7240642786185283
Tetrahedron,"Synthesis of the coumarin, sesibiricin",,10.1016/s0040-4039(01)97166-7,1971-01-01,0.7240642786185283
Tetrahedron,Regiospecific synthesis of rubranine,,10.1016/s0040-4039(01)97342-3,1971-01-01,0.7240642786185283
Tetrahedron,Synthesis of Polygodial,,10.1016/s0040-4039(01)96753-x,1971-01-01,0.7240642786185283
Tetrahedron,Formal synthesis of (+)-didemniserinolipid B,,10.1016/j.tetlet.2011.10.117,2011-10-26,0.7240642786185283
Tetrahedron,Synthesis of clavulones (claviridenones),,10.1016/s0040-4039(00)98135-8,1985-01-01,0.7240642786185283
Tetrahedron,"The synthesis of 2,6-dimethylenetricyclo[3.3.0.03,7]octane",,10.1016/s0040-4039(00)61875-0,1985-01-01,0.7240642786185283
Tetrahedron,",-dienes via acetylene carbocupration: synthesis of navel orangeworm pheromone",,10.1016/s0040-4039(00)98174-7,1985-01-01,0.7240642786185283
Tetrahedron,Synthesis of carbazoles via 2-vinylindoles.,,10.1016/s0040-4039(01)84606-2,1985-01-01,0.7240642786185283
Tetrahedron,Synthesis of mammeins and surangin a,,10.1016/s0040-4039(00)98874-9,1985-01-01,0.7240642786185283
Tetrahedron,A synthesis of -jasmone,,10.1016/s0040-4039(01)84555-x,1972-01-01,0.7240642786185283
Tetrahedron,Synthesis of 1-pyrroline 1-oxides analogous to pseudouridine,,10.1016/j.tetlet.2011.02.018,2011-02-10,0.7240642786185283
Synthesis,"Synthesis of 2-Sulfonylaminobenzimidazoles and 4,5-Dicyano-2-sulfonylaminoimidazoles from <i>N</i>-Dichloromethylenesulfonamides",,10.1055/s-1982-30036,2002-05-15,0.7240642786185283
Tetrahedron,Synthesis of 1-deoxy-l-gulonojirimycin and 1-deoxy-l-talonojirimycin,,10.1016/j.tetlet.2009.02.111,2009-02-22,0.7240642786185283
Tetrahedron,Synthesis of the starfish ganglioside AG2 pentasaccharide,,10.1016/j.tetlet.2009.08.071,2009-08-27,0.7240642786185283
Tetrahedron,Synthesis of silylated methylenecyclopropanes,,10.1016/s0040-4039(01)80802-9,1985-01-01,0.7240642786185283
Tetrahedron,The synthesis of the drugstore beetle pheromone (Stegobinone),,10.1016/s0040-4039(01)86330-9,1979-01-01,0.7240642786185283
Tetrahedron,The synthesis of olefins from β-ketosilanes,,10.1016/s0040-4039(01)85268-0,1972-01-01,0.7240642786185283
Tetrahedron,Oxophlorin (oxyporphyrin) synthesis,,10.1016/s0040-4039(01)84847-4,1972-01-01,0.7240642786185283
Tetrahedron,Toward the synthesis of brevipolide H,,10.1016/j.tetlet.2014.12.125,2015-01-03,0.7240642786185283
Tetrahedron,Synthesis of bicyclogermacrene and lepidozene,,10.1016/s0040-4039(00)98952-4,1985-01-01,0.7240642786185283
Tetrahedron,Synthesis of trichoverrol B,,10.1016/s0040-4039(00)94511-8,1983-01-01,0.7240642786185283
Tetrahedron,The synthesis of alpha-thiophene oligomers via organoboranes,,10.1016/s0040-4039(00)88257-x,1983-01-01,0.7240642786185283
Tetrahedron,Synthesis of [1.1.1.1]paracylophane,,10.1016/s0040-4039(00)88416-6,1983-01-01,0.7240642786185283
Tetrahedron,"The synthesis of d,l-phosphotryptophan",,10.1016/s0040-4039(00)94112-1,1983-01-01,0.7240642786185283
Tetrahedron,Synthesis of congeners of migrastatin and dorrigocin A from d-xylose,,10.1016/j.tetlet.2010.07.141,2010-08-04,0.7240642786185283
Tetrahedron,The synthesis of the endoperoxide of cyclooctatetraene via photosensitized singlet oxygenation,,10.1016/s0040-4039(00)88583-4,1982-01-01,0.7240642786185283
Tetrahedron,Synthesis of (−)-pinidinone,,10.1016/j.tetlet.2010.10.049,2010-10-15,0.7240642786185283
Tetrahedron,Synthesis of hydroxyethylene and ketomethylene dipeptide isosteres,,10.1016/s0040-4039(00)85908-0,1983-01-01,0.7240642786185283
Tetrahedron,Synthesis of milbemycins from avermectins,,10.1016/s0040-4039(00)87861-2,1983-01-01,0.7240642786185283
Tetrahedron,Synthesis and binding behaviors of monomethyl cucurbit[6]uril,,10.1016/j.tetlet.2011.06.110,2011-07-05,0.7240642786185283
Tetrahedron,The synthesis of (±)-verbascenine,,10.1016/s0040-4039(00)88197-6,1983-01-01,0.7240642786185283
Tetrahedron,Synthesis of β-trifluoromethylpyrroles,,10.1016/s0040-4039(00)81567-1,1983-01-01,0.7240642786185283
Tetrahedron,Synthesis of [2.2]cyclophanes by photodeselenative ringcontraction,,10.1016/s0040-4039(00)81990-5,1983-01-01,0.7240642786185283
Tetrahedron,2-Carbomethoxycyclopentenone as a synthon. synthesis of sarkomycin,,10.1016/s0040-4039(01)86536-9,1979-01-01,0.7240642786185283
Tetrahedron,"Synthesis of ketene S,S-acetals from thioamides",,10.1016/s0040-4039(01)95452-8,1979-01-01,0.7240642786185283
Synthesis,Synthesis of Vinylsilanes from Benzenesulfonylhydrazones,,10.1055/s-1976-24205,2002-09-12,0.7240642786185283
Tetrahedron,"Synthesis of (±)-asperdiol, a marine anticancer cembrenoid",,10.1016/s0040-4039(00)81900-0,1983-01-01,0.7240642786185283
Tetrahedron,Synthesis of bivittoside C genine,,10.1016/s0040-4039(00)88074-0,1983-01-01,0.7240642786185283
Tetrahedron,Synthesis of α-halo and α-deuterio-β-lactams,,10.1016/s0040-4039(00)81915-2,1983-01-01,0.7240642786185283
Tetrahedron,The synthesis of dl-Coriolin,,10.1016/s0040-4039(00)88317-3,1983-01-01,0.7240642786185283
Tetrahedron,Biogenetically patterned synthesis of Δ8(9-capnellene,,10.1016/s0040-4039(00)87002-1,1982-01-01,0.7240642786185283
Tetrahedron,Synthesis of azulene from 6-acyloxyfulvenes,,10.1016/s0040-4039(00)86871-9,1982-01-01,0.7240642786185283
Tetrahedron,Synthesis of inosinate trimer I2′p5′I2′pt′I and tetramer I2′p5′I2′p5′I2′p5′I,,10.1016/s0040-4039(00)85714-7,1982-01-01,0.7240642786185283
Tetrahedron,"Synthesis of the sulfones of leukotriene C4, D4, and E4",,10.1016/s0040-4039(00)87012-4,1982-01-01,0.7240642786185283
Tetrahedron,"Synthesis of 3,6-epoxy[1,5]dioxocines from 2-hydroxyaromatic benzaldehydes",,10.1016/j.tetlet.2011.08.095,2011-08-25,0.7240642786185283
Tetrahedron,"Synthesis and valence isomerizations of 1,1′-tetramethylenebicyclopropenyl",,10.1016/s0040-4039(01)91750-2,1974-01-01,0.7240642786185283
Tetrahedron,The synthesis of the rings A/B in withaferin A and other withanolides,,10.1016/s0040-4039(01)91822-2,1974-01-01,0.7240642786185283
Tetrahedron,Monofluorocarbene: The synthesis of fluorocyclopropanes,,10.1016/s0040-4039(00)75265-8,1975-01-01,0.7240642786185283
Tetrahedron,Synthesis of 8-azaprostaglandin E1 and E2,,10.1016/s0040-4039(00)91080-3,1975-01-01,0.7240642786185283
Tetrahedron,"Synthesis of unsymmetrical 4,4′-dialkyl-2,2′-bipyridines",,10.1016/s0040-4039(00)81318-0,1983-01-01,0.7240642786185283
Tetrahedron,Synthesis of 9-oxaprostaglandins,,10.1016/s0040-4039(01)92189-6,1974-01-01,0.7240642786185283
Tetrahedron,Synthesis of 9-thiaprostaglandins,,10.1016/s0040-4039(01)92190-2,1974-01-01,0.7240642786185283
Tetrahedron,"Synthesis of streptolidine (roseonine, geamine)",,10.1016/s0040-4039(01)82507-7,1974-01-01,0.7240642786185283
Tetrahedron,The synthesis of aspersitin,,10.1016/s0040-4039(00)81973-5,1983-01-01,0.7240642786185283
Tetrahedron,A biomimetic synthesis of the skeleton of trigonoliimine C,,10.1016/j.tetlet.2011.08.087,2011-09-11,0.7240642786185283
Tetrahedron,"A 1,5-benzothiazepine synthesis",,10.1016/j.tetlet.2011.01.098,2011-02-02,0.7240642786185283
Tetrahedron,The synthesis of demthylgorgosterol,,10.1016/s0040-4039(01)86034-2,1979-01-01,0.7240642786185283
Tetrahedron,Elaeocarpus Alkaloids. The Synthesis of dl-Elaeokanine-A and dl-Elaeokanine-C.,,10.1016/s0040-4039(01)86614-4,1979-01-01,0.7240642786185283
Tetrahedron,Amidoalkylation of dienes with adducts of glyoxylic - synthesis of α-acylamino-γ-alkenyl-γ-butyrolactones,,10.1016/s0040-4039(00)81575-0,1983-01-01,0.7240642786185283
Tetrahedron,Tellurium extrusion: Synthesis of benzocyclobutene and naphto[b]cyclobutene,,10.1016/s0040-4039(00)72313-6,1975-01-01,0.7240642786185283
Tetrahedron,Synthesis of deoxyharringtonine,,10.1016/s0040-4039(01)82194-8,1974-01-01,0.7240642786185283
Tetrahedron,Synthesis of the diacid sidechain of deoxyharringtonine,,10.1016/s0040-4039(01)87276-2,1973-01-01,0.7240642786185283
Tetrahedron,"Synthesis of 2,4-methanoproline",,10.1016/0040-4039(80)80078-5,1980-01-01,0.7240642786185283
Tetrahedron,Chemomicrobial synthesis of (R)- and (S)-lavandulol,,10.1016/j.tetlet.2011.06.072,2011-06-28,0.7240642786185283
Tetrahedron,The synthesis of rhazinilam,,10.1016/s0040-4039(01)87657-7,1973-01-01,0.7240642786185283
Tetrahedron,Synthesis of (±)-hepta-O-methylfukugetin and hepta-O-methylsaharanflavone,,10.1016/s0040-4039(01)94321-7,1972-01-01,0.7240642786185283
Tetrahedron,Synthesis of dihydroactiniolide and a trimethyloctalenedione,,10.1016/s0040-4039(01)87649-8,1973-01-01,0.7240642786185283
Tetrahedron,"Synthesis of 1,1,4,4-tetraalkoxy-1,3-butadienes",,10.1016/s0040-4039(01)82395-9,1974-01-01,0.7240642786185283
Tetrahedron,Synthesis of quercetin 3-O-β-d-apiofuranosyl-(1→2)-[α-l-rhamnopyranosyl-(1→6)]-β-d-glucopyranoside,,10.1016/j.tetlet.2011.04.040,2011-04-19,0.7240642786185283
Tetrahedron,Synthesis of (+)-Isoeremolactone.,,10.1016/s0040-4039(00)85934-1,1983-01-01,0.7240642786185283
Tetrahedron,The synthesis of (±)-cycloprodigiosin,,10.1016/s0040-4039(01)80165-9,1984-01-01,0.7240642786185283
Tetrahedron,Synthesis and electrocyclisation of hendecafulvadienes “azulenoid” 14π-annulenes,,10.1016/s0040-4039(00)81868-7,1983-01-01,0.7240642786185283
Tetrahedron,"Tetraacylation of isobutene: first synthesis of 1,3,6,8-tetramethyl-2,7-naphthyridine",,10.1016/s0040-4039(00)99925-8,1984-01-01,0.7240642786185283
Tetrahedron,"Synthesis of 5S,12S - diHETE (LTBx)",,10.1016/s0040-4039(01)80119-2,1984-01-01,0.7240642786185283
Tetrahedron,Synthesis of ± 8- and 9-HETEs,,10.1016/s0040-4039(01)91141-4,1984-01-01,0.7240642786185283
Tetrahedron,Synthesis on templates : Regiospecific synthesis of imidazoles,,10.1016/s0040-4039(01)91416-9,1984-01-01,0.7240642786185283
Tetrahedron,Formal synthesis of (±)-perhydrohistrionicotoxin,,10.1016/s0040-4039(01)90211-4,1984-01-01,0.7240642786185283
Tetrahedron,Synthesis of isoclovene,,10.1016/s0040-4039(00)86281-4,1983-01-01,0.7240642786185283
Tetrahedron,"Synthesis of some 3,7-dicyano-1,5-dimethylsemibullvalenes",,10.1016/s0040-4039(00)94149-2,1983-01-01,0.7240642786185283
Tetrahedron,Synthesis of a tetrahydrofuranone prostaglandin analog,,10.1016/s0040-4039(01)91726-5,1974-01-01,0.7240642786185283
Tetrahedron,Synthesis of dihydroangustine,,10.1016/s0040-4039(01)87349-4,1973-01-01,0.7240642786185283
Tetrahedron,The synthesis of bellendine,,10.1016/s0040-4039(01)87397-4,1973-01-01,0.7240642786185283
Tetrahedron,Synthesis of γ-acoradiene (α-alaskene) and δ-acoradiene,,10.1016/s0040-4039(01)87226-9,1973-01-01,0.7240642786185283
Tetrahedron,"Additions to cyclobutenes: synthesis of 5-azabicyclo[2.1.0]pentanes, 2-azabicyclo[ 2.2.0]hexanes, and 1-azaspiro[3.3]heptanes",,10.1016/s0040-4039(01)87016-7,1973-01-01,0.7240642786185283
Tetrahedron,Synthesis of N-(tosyl)azetidin-2-imines,,10.1016/s0040-4039(00)77413-2,1980-01-01,0.7240642786185283
Tetrahedron,A formal synthesis of modhephene,,10.1016/s0040-4039(01)91215-8,1984-01-01,0.7240642786185283
Tetrahedron,Acyclic stereocontrolled synthesis of (−)-detoxinine,,10.1016/s0040-4039(01)90201-1,1984-01-01,0.7240642786185283
Tetrahedron,Synthesis of the rifamycin chromophore,,10.1016/s0040-4039(00)81917-6,1983-01-01,0.7240642786185283
Tetrahedron,"Synthesis of 1,11α-ethano corticosteroids",,10.1016/s0040-4039(00)94152-2,1983-01-01,0.7240642786185283
Tetrahedron,A synthesis of 3-deazathymidine,,10.1016/s0040-4039(01)96324-5,1973-01-01,0.7240642786185283
Tetrahedron,Synthesis of a stereoisomer of ptychanolide,,10.1016/s0040-4039(00)88292-1,1983-01-01,0.7240642786185283
Tetrahedron,"Synthesis of 8,9-leukotriene C3 and D3",,10.1016/s0040-4039(00)85929-8,1983-01-01,0.7240642786185283
Tetrahedron,"Regiospecific synthesis of 1,3-diazaazulenes",,10.1016/s0040-4039(01)91824-6,1974-01-01,0.7240642786185283
Tetrahedron,Synthesis of prumycin,,10.1016/s0040-4039(00)75275-0,1975-01-01,0.7240642786185283
Tetrahedron,Diaryl sulphones : a synthesis from arylthalliums,,10.1016/s0040-4039(01)95525-x,1979-01-01,0.7240642786185283
Tetrahedron,Synthesis of fluorescent coumarin triazolylglycosides,,10.1016/j.tetlet.2011.06.016,2011-06-25,0.7240642786185283
Tetrahedron,Furans in synthesis 4. Silyl furans as butenolide equivalents,,10.1016/s0040-4039(01)81464-7,1984-01-01,0.7240642786185283
Tetrahedron,"Enantiospecific Synthesis of Swainsonine, (1S, 2R, 8R, 8aR)-1,2,8-trihydroxyoctahydroindolizine, from D-mannose",,10.1016/s0040-4039(01)90059-0,1984-01-01,0.7240642786185283
Tetrahedron,The synthesis of ruscodibenzofuran,,10.1016/s0040-4039(01)94516-2,1979-01-01,0.7240642786185283
Tetrahedron,"Synthesis of aporphine, morphinandienone and dibinzindolizinium alkaloids through benzyne cyclisation",,10.1016/s0040-4039(01)96283-5,1973-01-01,0.7240642786185283
Tetrahedron,Synthesis of (±)-pentalenene,,10.1016/s0040-4039(01)81354-x,1984-01-01,0.7240642786185283
Tetrahedron,A stereocontrolled synthesis of monofluoro ketomethylene dipeptide isosteres,,10.1016/s0040-4039(98)00783-7,1998-06-01,0.7240642786185283
Tetrahedron,Synthesis of hexagonal shape-persistent cyclophane with D symmetry,,10.1016/j.tetlet.2016.07.086,2016-07-30,0.7240642786185283
Tetrahedron,Synthesis of isobatzelline B,,10.1016/s0040-4039(97)10591-3,1998-02-01,0.7240642786185283
Synthesis,Synthesis of 2-Alkoxy-3-alkoxycarbonyl-3<i>H</i>-azepines,,10.1055/s-1974-23357,1974-01-01,0.7240642786185283
Synthesis,Synthesis of 2-Alkenylthiophenols,,10.1055/s-1974-23427,1974-01-01,0.7240642786185283
Synthesis,A Regiospecific Synthesis of α-Methoxystilbenes,,10.1055/s-1974-23376,1974-01-01,0.7240642786185283
Tetrahedron,Synthesis of 2-oxiranyl and aziridinyl thiazoles,,10.1016/s0040-4039(98)01727-4,1998-10-01,0.7240642786185283
Tetrahedron,Synthesis of epoxy-terminated dialkyl disulfides for polymerizable self-assembled monolayers,,10.1016/s0040-4039(98)01785-7,1998-11-01,0.7240642786185283
Tetrahedron,"Synthesis of expanded planar dehydrobenzoannulenes: Weakly diatropic, weakly paratropic, or atropic?",,10.1016/s0040-4039(98)01583-4,1998-09-01,0.7240642786185283
Tetrahedron,First synthesis of BU-4664L,,10.1016/j.tetlet.2015.08.070,2015-08-25,0.7240642786185283
Tetrahedron,Synthesis and microbial hydroxylation of some azabicycloalkanes,,10.1016/s0040-4039(97)10876-0,1998-03-01,0.7240642786185283
Tetrahedron,Synthesis of atovaquone,,10.1016/s0040-4039(98)01691-8,1998-10-01,0.7240642786185283
Tetrahedron,"Synthesis of (4R,15R,16R,21S)- and (4R,15S,16S,21S)-rollicosin",,10.1016/j.tetlet.2005.04.144,2005-05-26,0.7240642786185283
Synthesis,Synthesis of Diimines and Dihydropyrimidines,,10.1055/s-1974-23417,1974-01-01,0.7240642786185283
Synthesis,Synthesis of Unsubstituted Amidrazones,,10.1055/s-1974-23385,1974-01-01,0.7240642786185283
Synthesis,"Synthesis of<i>s</i>-Triazolo [4,3-<i>a</i>]-<i>s</i>-triazines and their Isomerisation to<i>s</i>-Triazolo [2,3-<i>a</i>]-<i>s</i>-triazines*",,10.1055/s-1974-23451,1974-01-01,0.7240642786185283
Synthesis,Synthesis of<i>O</i>-Arenesulfonyl- and<i>O</i>-Arenecarbonyl-hydroxylamines,,10.1055/s-1975-23927,1975-01-01,0.7240642786185283
Synthesis,"Selenium Heterocycles; Part I. Synthesis of 2,3-Dihydroselenolo[2,3-<i>b</i>]quinolines",,10.1055/s-1977-24289,1977-01-01,0.7240642786185283
Synthesis,Synthesis of Phospholiposteroids. Phosphatidylcholesterol,,10.1055/s-1977-24524,1977-01-01,0.7240642786185283
Tetrahedron,Synthesis of sulfobacin B,,10.1016/s0040-4039(98)01178-2,1998-08-01,0.7240642786185283
Tetrahedron,"Synthesis and thermolysis of hexacoordinate 1,2-oxaphosphetanides",,10.1016/s0040-4039(96)02369-6,1997-01-01,0.7240642786185283
Tetrahedron,"Synthesis and scintillating efficiencies of 4-functionalised-2,5-diphenyloxazoles",,10.1016/s0040-4039(97)10435-x,1997-12-01,0.7240642786185283
Tetrahedron,Unsaturated hetero chains -VII. The synthesis of 1-thioacyl-oligonitriles,,10.1016/s0040-4039(97)01226-4,1997-08-01,0.7240642786185283
Tetrahedron,Synthesis of a branched oligosaccharide by remote glycosidation,,10.1016/s0040-4039(96)02196-x,1997-01-01,0.7240642786185283
Tetrahedron,Synthesis of polysubstituted-2-naphthols,,10.1016/j.tetlet.2005.05.020,2005-05-25,0.7240642786185283
Tetrahedron,A formal synthesis of brassinolide,,10.1016/s0040-4039(97)00474-7,1997-04-01,0.7240642786185283
Tetrahedron,First and stereoflexible synthesis of vinylogous Taxol side chains,,10.1016/s0040-4039(97)10346-x,1997-12-01,0.7240642786185283
Tetrahedron,Synthesis of (+)-sorokinianin,,10.1016/s0040-4039(97)01337-3,1997-08-01,0.7240642786185283
Tetrahedron,A formal synthesis of (+)-brefeldin A,,10.1016/s0040-4039(98)01078-8,1998-07-01,0.7240642786185283
Tetrahedron,Synthesis of thiolesters from thioacetylenes,,10.1016/s0040-4039(98)00531-0,1998-05-01,0.7240642786185283
Tetrahedron,"The synthesis of 2′-homouridine, its incorporation into a dinucleoside monophosphate and hydrolytic behaviour of the dimer",,10.1016/s0040-4039(98)01478-6,1998-09-01,0.7240642786185283
Tetrahedron,"Synthesis of cytotoxic cyanobactin, Wewakazole B",,10.1016/j.tetlet.2017.02.012,2017-02-09,0.7240642786185283
Tetrahedron,Synthesis of oligomers of calix[4]arene with methylene bridge at the upper rims,,10.1016/s0040-4039(98)01168-x,1998-08-01,0.7240642786185283
Tetrahedron,"Synthesis of cationic lipids from 1,2,4-butanetriol",,10.1016/s0040-4039(98)02381-8,1999-01-01,0.7240642786185283
Tetrahedron,Synthesis of carbohydrate functionalised n-propoxy-Calix[4]arenes,,10.1016/s0040-4039(98)02136-4,1998-12-01,0.7240642786185283
Tetrahedron,Synthesis of (+)-coronarin E,,10.1016/s0040-4039(98)00861-2,1998-06-01,0.7240642786185283
Tetrahedron,Stereocontrolled synthesis of the CD subunit of the marine macrolide altohyrtin A,,10.1016/s0040-4039(98)00686-8,1998-06-01,0.7240642786185283
Tetrahedron,Stereocontrolled synthesis of all-(E)- and (8Z)-anhydroretinol,,10.1016/s0040-4039(98)01101-0,1998-07-01,0.7240642786185283
Tetrahedron,Enantiospecific synthesis of tetrasubstituted δ-lactones,,10.1016/s0040-4039(98)02243-6,1998-12-01,0.7240642786185283
Tetrahedron,Synthesis of isotopically labelled cardiolipins,,10.1016/s0040-4039(97)10829-2,1998-03-01,0.7240642786185283
Tetrahedron,A synthesis of 1-pyridylnaphthalene lignan analogs,,10.1016/s0040-4039(97)10849-8,1998-03-01,0.7240642786185283
Tetrahedron,"Synthesis of (−)-(2R,3R,6S)-irnigaine and (+)-(2R,3R,6S)-N-methylirnigaine",,10.1016/s0040-4039(98)00297-4,1998-04-01,0.7240642786185283
Tetrahedron,Synthesis of xestobergsterol A from dehydroepiandrosterone,,10.1016/j.tetlet.2005.07.042,2005-07-29,0.7240642786185283
Tetrahedron,Synthesis of D-erythro-sphingosine and D-erythro-sphinganine via 3-ketosphinganine,,10.1016/s0040-4039(98)00733-3,1998-06-01,0.7240642786185283
Tetrahedron,"Synthesis of diacylglycerol analogs of phosphatidylinositol 3,4,5-trisphosphate",,10.1016/s0040-4039(98)02151-0,1998-12-01,0.7240642786185283
Tetrahedron,"Synthesis of 3,4,5-trimethoxyphenyl 5″-O-caffeoyl-β-d-erythro-apiofuranosyl-(1→6)-β-d-glucopyranoside: Kelampayoside B",,10.1016/s0040-4039(98)00673-x,1998-06-01,0.7240642786185283
Tetrahedron,Regiospecific synthesis of 3-organosulfonyloxy-2-alkanones,,10.1016/s0040-4039(98)00451-1,1998-05-01,0.7240642786185283
Tetrahedron,Synthesis of the tripeptide (C1–N12) and hydroxylated hexadecene (C26–C41) domains of sanglifehrin A and C,,10.1016/s0040-4039(99)01539-7,1999-10-01,0.7240642786185283
Tetrahedron,Synthesis of targetable cationic amphiphiles,,10.1016/s0040-4039(99)01558-0,1999-10-01,0.7240642786185283
Synthesis,"Synthesis of [1,3]Thiazolo[3,2-<i>b</i>]-<i>s</i>-triazoles and [1,3]Thiazolo[2,3-<i>c</i>]-<i>s</i>-triazoles",,10.1055/s-1979-28552,1979-01-01,0.7240642786185283
Tetrahedron,Synthesis of the C42–C52 part of ciguatoxin CTX3C,,10.1016/j.tetlet.2005.09.163,2005-10-18,0.7240642786185283
Synthesis,"Synthesis of α-Alkoxy-, α-Aryloxy-, and α-Benzyloxyacetaldehydes",,10.1055/s-1979-28618,1979-01-01,0.7240642786185283
Synthesis,"Synthesis of<i>O</i>,<i>O</i>-Dialkyl 1-Aminoalkanephosphonates",,10.1055/s-1980-29311,1980-01-01,0.7240642786185283
Synthesis,The Synthesis of Triazines from<i>N</i>-Cyanoamidines,,10.1055/s-1980-29230,1980-01-01,0.7240642786185283
Synthesis,"Synthesis of α-Monohalo- and α,α-Dihaloaldehydes from Carbenoids",,10.1055/s-1980-29153,1980-01-01,0.7240642786185283
Tetrahedron,A brief synthesis of the Aplasmomycin tetrahydrofuran,,10.1016/s0040-4039(00)00614-6,2000-06-01,0.7240642786185283
Tetrahedron,Synthesis of alkylphenols and alkylcatechols from the marine mollusc Haminoea callidegenita,,10.1016/s0040-4039(00)00532-3,2000-05-01,0.7240642786185283
Tetrahedron,"A biomimetic synthesis of the indolo[3,2-j]phenanthridine alkaloid, calothrixin B",,10.1016/j.tetlet.2006.06.077,2006-07-08,0.7240642786185283
Tetrahedron,The first synthesis of C-glucotropaeolin,,10.1016/s0040-4039(99)01416-1,1999-10-01,0.7240642786185283
Tetrahedron,The first synthesis of biatriosporin D,,10.1016/j.tetlet.2018.04.027,2018-04-11,0.7240642786185283
Synthesis,Synthesis of Exaltolide (Pentadecanolide) and Thioexaltolide from Cyclododecanone,,10.1055/s-1980-28929,1980-01-01,0.7240642786185283
Tetrahedron,Synthesis of hemicyanine dyes for ‘click’ bioconjugation,,10.1016/j.tetlet.2005.01.066,2005-02-01,0.7240642786185283
Tetrahedron,Synthesis of γ-lactams via trifluoromethylative aminocarbonylation of unactivated olefins,,10.1016/j.tetlet.2019.151479,2019-12-05,0.7240642786185283
Tetrahedron,Synthesis of unsaturated silyl nitronates via the silylation of conjugated nitroalkenes,,10.1016/j.tetlet.2018.07.011,2018-07-03,0.7240642786185283
Tetrahedron,Synthesis of azacalix[4]arene betaine,,10.1016/s0040-4039(99)01230-7,1999-08-01,0.7240642786185283
Synthesis,Synthesis of some Cyclohepta-thiophenes,,10.1055/s-1977-24352,1977-01-01,0.7240642786185283
Tetrahedron,Synthesis of (−)-alantrypinone,,10.1016/s0040-4039(99)01005-9,1999-07-01,0.7240642786185283
Tetrahedron,"“Geländer” macrocycles: Synthesis, chirality and racemisation barriers",,10.1016/j.tetlet.2018.12.047,2018-12-20,0.7240642786185283
Tetrahedron,Synthesis of the glycosyl phosphatidyl inositol anchor of rat brain Thy-1,,10.1016/s0040-4039(98)02579-9,1999-01-01,0.7240642786185283
Tetrahedron,Synthesis of oxazolinyl aziridines,,10.1016/s0040-4039(99)01212-5,1999-08-01,0.7240642786185283
Synthesis,Synthesis of Monodeuterioacetylene*,,10.1055/s-1976-23976,1976-01-01,0.7240642786185283
Tetrahedron,Synthesis of 2-(alkylamino)benzimidazoles,,10.1016/s0040-4039(98)02592-1,1999-02-01,0.7240642786185283
Tetrahedron,Synthesis of phosphocarnitine,,10.1016/s0040-4039(99)00010-6,1999-02-01,0.7240642786185283
Tetrahedron,"A synthesis of l-α-phosphatidyl-d-myo-inositol 4,5-bisphosphate (4,5-PIP2) and glyceryl lipid analogs",,10.1016/s0040-4039(99)01877-8,1999-12-01,0.7240642786185283
Synthesis,"Synthesis of<i>N</i>,<i>N</i>′-Dithiobis-, Sulfinylbis-, and Sulfonylbis-sulfoximines",,10.1055/s-1975-23830,1975-01-01,0.7240642786185283
Synthesis,"Thienoquinolines Part 1. Synthesis of Thieno[2,3-<i>b</i>]-quinolines",,10.1055/s-1976-24006,1976-01-01,0.7240642786185283
Synthesis,The Synthesis of a β-Methylene-γ-spirolactone,,10.1055/s-1977-24286,1977-01-01,0.7240642786185283
Synthesis,Synthesis of γ-Acetoxytiglicaldehyde from Isoprene,,10.1055/s-1977-24520,1977-01-01,0.7240642786185283
Synthesis,"Synthesis of 2,5-Dialkylpyrrolidines via Metallated Nitrosamines, A Constituent of Fire Ant Venom",,10.1055/s-1976-24115,1976-01-01,0.7240642786185283
Synthesis,Synthesis of α-Hydroxyacetals,,10.1055/s-1977-24486,1977-01-01,0.7240642786185283
Synthesis,Synthesis of 2-(2-Oxoalkyl)-quinolines and 4-(2-Oxoalkyl)-quinolines,,10.1055/s-1976-24196,1976-01-01,0.7240642786185283
Tetrahedron,Synthesis of 8-deoxypumiliotoxin 193H and 9-deoxyhomopumiliotoxin 207O,,10.1016/j.tetlet.2018.09.015,2018-09-08,0.7240642786185283
Tetrahedron,"Synthesis of 1,2-dioxanes, 1,2,4-trioxanes, and 1,2,4-trioxepanes via cyclizations of unsaturated hydroperoxyacetals",,10.1016/0040-4039(95)02199-x,1996-01-01,0.7240642786185283
Tetrahedron,The first synthesis of diaxial bislactone furofuran lignan,,10.1016/0040-4039(95)01599-d,1995-11-01,0.7240642786185283
Tetrahedron,Synthesis of phospholipid-oligodeoxyribonucleotide conjugates,,10.1016/0040-4039(95)00292-k,1995-04-01,0.7240642786185283
Tetrahedron,Kemp's Triacid Scaffolding for Synthesis of Combinatorial Nonpeptide Uncoded Libraries,,10.1016/00404-0399(50)1370w-,1995-09-11,0.7240642786185283
Tetrahedron,The synthesis and conformation of dihydroxy-cyclo(d-Pro-l-Pro-d-Pro-l-Pro),,10.1016/0040-4039(95)00022-5,1995-02-01,0.7240642786185283
Tetrahedron,"Synthesis of curacin A, an antimitotic cyclopropane-thiazoline from the marine cyanobacterium Lyngbya majuscula",,10.1016/0040-4039(96)01616-4,1996-09-01,0.7240642786185283
Tetrahedron,"Synthesis and characterisation of the methanofullerenes, C60(CHCN) and C60(CBr2)",,10.1016/0040-4039(95)02256-2,1996-02-01,0.7240642786185283
Tetrahedron,Synthesis of a ribofuranosyl cation mimic,,10.1016/0040-4039(96)00202-x,1996-03-01,0.7240642786185283
Tetrahedron,Synthesis of archaebacterial lipid C20 chirons,,10.1016/s0040-4039(97)10186-1,1997-11-01,0.7240642786185283
Tetrahedron,Synthesis of 5-chloropyrrole carboxaldehydes from 5-oxopyrrolidine carboxamides,,10.1016/s0040-4039(97)00597-2,1997-05-01,0.7240642786185283
Tetrahedron,Synthesis of Tetrasubstituted β-Lactones,,10.1016/s0040-4039(97)10120-4,1997-11-01,0.7240642786185283
Tetrahedron,Synthesis of the C1C9 segment of epothilons,,10.1016/s0040-4039(96)02493-8,1997-02-01,0.7240642786185283
Tetrahedron,Enantiospecific synthesis of (+)-puupehenone from (−)-sclareol and protocatechualdehyde,,10.1016/s0040-4039(97)00305-5,1997-03-01,0.7240642786185283
Tetrahedron,"Synthesis of N,N′-Etheno-Bridged Porphycene Hydroperchlorates",,10.1016/s0040-4039(97)00381-x,1997-04-01,0.7240642786185283
Tetrahedron,Stereocontrolled synthesis of α-2′-deoxyribonucleosides,,10.1016/s0040-4039(97)10251-9,1997-11-01,0.7240642786185283
Tetrahedron,Synthesis of combretastatins A-1 and B-1,,10.1016/j.tetlet.2005.12.037,2005-12-28,0.7240642786185283
Tetrahedron,First synthesis of an expanded calixpyrrole,,10.1016/s0040-4039(97)10275-1,1997-12-01,0.7240642786185283
Synthesis,Synthesis of Homo- and Heterobiarylmethylamines,International audience,10.1055/s-2006-942353,2006-05-23,0.7240642786185283
Tetrahedron,"Synthesis of α-fluorinated-α,α-difunctionalized sulfides and sulfones",,10.1016/0040-4039(96)00186-4,1996-04-01,0.7240642786185283
Tetrahedron,"Synthesis of 2,3-dihydropyridines, cyclobutanopyrrolines and quinolines from lithiated allenes and isothiocyanates",,10.1016/s0040-4039(97)01591-8,1997-09-01,0.7240642786185283
Tetrahedron,Synthesis of azasugars. Part 1 isomerization of polyhydroxylated piperidines,,10.1016/0040-4039(96)00096-2,1996-03-01,0.7240642786185283
Tetrahedron,Synthesis of constanolactone E,,10.1016/0040-4039(96)01692-9,1996-10-01,0.7240642786185283
Tetrahedron,Polypyrroles in three dimensions. The synthesis of tripyrrane-strapped 2-aminophenylporphyrins,,10.1016/0040-4039(96)01423-2,1996-09-01,0.7240642786185283
Tetrahedron,Synthesis of C-disaccharides from C-formyl glycosides,,10.1016/0040-4039(96)01667-x,1996-10-01,0.7240642786185283
Tetrahedron,"A synthesis of cyclo-2,3-diphospho-D-glycerate from D-mannitol",,10.1016/0040-4039(95)02154-x,1996-01-01,0.7240642786185283
Tetrahedron,Synthesis of the 6- and 7-hydroxylated cocaines and pseudococaines,,10.1016/0040-4039(96)01123-9,1996-07-01,0.7240642786185283
Tetrahedron,"Synthesis of 5-methylene-1,3-cyclohexadienes (o-isotoluenes) via electrocyclization of (4Z)-1,2,4,6-heptatetraenes",,10.1016/0040-4039(96)00774-5,1996-06-01,0.7240642786185283
Tetrahedron,Synthesis of carboranyl polyamines for DNA targeting,,10.1016/s0040-4039(97)82942-5,1996-12-01,0.7240642786185283
Tetrahedron,First synthesis of (+)-brazilane from (+)-brazilin,,10.1016/0040-4039(96)00288-2,1996-04-01,0.7240642786185283
Tetrahedron,Biomimetic synthesis of the microbial elicitor syringolide 2,,10.1016/0040-4039(96)00611-9,1996-05-01,0.7240642786185283
Tetrahedron,Synthesis of unsymmetrical dipyrrolyl sulfides,,10.1016/0040-4039(96)00437-6,1996-04-01,0.7240642786185283
Tetrahedron,Synthesis of the C(1)-C(9) segment of the cytotoxic macrolides epothilon A and B,,10.1016/s0040-4039(96)02156-9,1996-12-01,0.7240642786185283
Tetrahedron,Synthesis of uracil polyoxin C from uridine,,10.1016/0040-4039(95)02116-7,1996-01-01,0.7240642786185283
Tetrahedron,The First Synthesis of Diaxial Bislactone Furofuran Lignan,,10.1016/00404-0399(50)1599d-,1995-11-06,0.7240642786185283
Tetrahedron,Kemp's Triacid Scaffolding for Synthesis of Combinatorial Nonpeptide Uncoded Libraries,,10.1016/0040-4039(95)01370-w,1995-01-16,0.7240642786185283
Tetrahedron,Synthesis of the cyclohexene segment of portimine,,10.1016/j.tetlet.2018.12.063,2018-12-26,0.7240642786185283
Tetrahedron,Formal synthesis of Pellasoren – A,,10.1016/j.tetlet.2018.09.035,2018-09-14,0.7240642786185283
Tetrahedron,Synthesis of (+)- and (−)-milnaciprans and their conformationally restricted analogs,,10.1016/0040-4039(95)02221-x,1996-01-01,0.7240642786185283
Tetrahedron,Synthesis of acylphosphates of purine ribonucleosides,,10.1016/s0040-4039(96)02016-3,1996-11-01,0.7240642786185283
Tetrahedron,First stepwise synthesis of cellulose analogs,,10.1016/s0040-4039(96)02186-7,1996-12-01,0.7240642786185283
Tetrahedron,Benzothiazines in synthesis. Formal synthesis of erogorgiaene,,10.1016/j.tetlet.2005.03.184,2005-04-13,0.7240642786185283
Tetrahedron,"Enantiospecific synthesis of 5′,5′,5′-trifluoro-5′-deoxyneplanocin A",,10.1016/j.tetlet.2005.10.064,2005-11-05,0.7240642786185283
Tetrahedron,Synthesis of (+)-8-Deoxyvernolepin,,10.1016/s0040-4039(97)01540-2,1997-09-01,0.7240642786185283
Tetrahedron,The synthesis of (+)-pericosine B,,10.1016/s0040-4039(98)01989-3,1998-11-01,0.7240642786185283
Tetrahedron,Synthesis of covalent head-to-tail dimers of vancomycin,,10.1016/s0040-4039(98)00895-8,1998-07-01,0.7240642786185283
Tetrahedron,α-Iodocycloalkenones: Synthesis of (±)-epibatidine,,10.1016/s0040-4039(98)00187-7,1998-04-01,0.7240642786185283
Tetrahedron,Synthesis of 5-pentafluorosulfanyl indazoles,,10.1016/j.tetlet.2017.10.031,2017-10-14,0.7240642786185283
Synthesis,"Synthesis of 1,2,3-Trimethyl-, 1,2,3,7-Tetramethyl-, and 1,2,3,5,6,7-Hexamethylnaphthalenes",,10.1055/s-1973-22275,1973-01-01,0.7240642786185283
Synthesis,Synthesis of Dialkyl 1-Alkoxyvinylphosphonates,,10.1055/s-1973-22261,1973-01-01,0.7240642786185283
Tetrahedron,Synthesis of the C1-C9 Segment of Epothilons.,,,1997-01-01,0.7240642786185283
Tetrahedron,Synthesis of a head to head cholaphane,,10.1016/s0040-4039(97)01100-3,1997-07-01,0.7240642786185283
Tetrahedron,"An enantiocontrolled synthesis of pyrrolizidines, (−)-platynecine and (−)-hadinecine",,10.1016/s0040-4039(96)02371-4,1997-01-01,0.7240642786185283
Tetrahedron,The synthesis of 3-amidinio-2-aminopyridine-4-carboxylates,,10.1016/s0040-4039(97)00899-x,1997-06-01,0.7240642786185283
Synthesis,Synthesis of Dialkyl Epoxyethylphosphonates,,10.1055/s-1971-21664,1971-01-01,0.7240642786185283
Synthesis,Synthesis of<i>o</i>- and<i>p</i>-Diazophenol,,10.1055/s-1971-21763,1971-01-01,0.7240642786185283
Synthesis,Synthesis of N-Alkylsulfonylphthalimides from Phthalimide and Sulfenes,,10.1055/s-1970-21639,1970-01-01,0.7240642786185283
Synthesis,"Synthesis of Triflates of 2,4-Dinitrophenol and N-Hydroxysuccinimide",,10.1055/s-1971-21778,1971-01-01,0.7240642786185283
Synthesis,Synthesis of Unsymmetrical Polychlorinated Biphenyls,,10.1055/s-1973-22166,1973-01-01,0.7240642786185283
Synthesis,Synthesis of Azoalkanes,,10.1055/s-1972-21965,1972-01-01,0.7240642786185283
Synthesis,"Synthesis of 2,5,8-Trimethylphenalene",,10.1055/s-1974-23372,1974-01-01,0.7240642786185283
Tetrahedron,"Synthesis of (3aR,8S,8bS,2′R)-(+)-sorgolactone and its stereoisomers, the germination stimulant from sorghum bicolor",,10.1016/s0040-4039(97)10078-8,1997-11-01,0.7240642786185283
Tetrahedron,Synthesis of nor-norambracetal,,10.1016/0040-4039(96)00697-1,1996-05-01,0.7240642786185283
Tetrahedron,First synthesis of conagenin diastereoisomers,,10.1016/0040-4039(96)00303-6,1996-04-01,0.7240642786185283
Tetrahedron,The synthesis of conjugated diacetylene monomers for the fabrication of polymerized monolayer assemblies,,10.1016/s0040-4039(96)02262-9,1997-01-01,0.7240642786185283
Tetrahedron,The Biomimetic Synthesis of Marine Epoxylipids : Bisepoxides to Tetrahydrofurans,,10.1016/s0040-4039(97)01806-6,1997-10-01,0.7240642786185283
Tetrahedron,Synthesis of (+)-squamostanal-A: a bioactive acetogenin of Annonaceae,,10.1016/0040-4039(96)00064-0,1996-03-01,0.7240642786185283
Tetrahedron,Synthesis of C-disaccharides via glucal dimerisation,,10.1016/s0040-4039(96)02093-x,1996-12-01,0.7240642786185283
Tetrahedron,Dilactams. Synthesis of nonsymmetrical dibenzodiazocinediones 1,,10.1016/j.tetlet.2003.12.079,2004-01-16,0.7240642786185283
Synthesis,Synthesis of α-Bromosulfoxides,,10.1055/s-1970-21646,1970-01-01,0.7240642786185283
Synthesis,Synthesis of D- and L-1-(4-Hydroxyphenyl)-2-isopropylaminoethanol,,10.1055/s-1970-21628,1970-01-01,0.7240642786185283
Tetrahedron,Synthesis of 5′-C-Hydroxyalkylthymidines and Their Incorporation into Oligodeoxynucleotides,,10.1016/s0040-4039(97)00386-9,1997-04-01,0.7240642786185283
Tetrahedron,Synthesis of peptidosialosides and peptidosaccharides,,10.1016/s0040-4039(97)00569-8,1997-05-01,0.7240642786185283
Tetrahedron,Synthesis of dispacamide from the marine sponge agelas dispar,,10.1016/s0040-4039(97)10387-2,1997-12-01,0.7240642786185283
Tetrahedron,Synthesis of triisopropyl α-(trimethylsilyloxy)propargyl stannanes,,10.1016/0040-4039(95)02212-0,1996-01-01,0.7240642786185283
Tetrahedron,"4-O-TfO-2,3-anhydro-β-L-ribopyranosides as chiron: A formal synthesis of canadensolide",,10.1016/s0040-4039(96)02026-6,1996-11-01,0.7240642786185283
Tetrahedron,"Synthesis of incrustasterols, two cytotoxic polyoxygenated sponge steroids",,10.1016/0040-4039(96)00932-x,1996-07-01,0.7240642786185283
Tetrahedron,A serendipitous synthesis of cyclokojibiose,,10.1016/0040-4039(96)00653-3,1996-05-01,0.7240642786185283
Tetrahedron,Synthesis of Semi-Rigid Analogs of Anabasine,,10.1016/s0040-4039(96)02058-8,1996-12-01,0.7240642786185283
Tetrahedron,"Synthesis of Hantsch 1,4-dihydropyridines by fermenting bakers’ yeast",,10.1016/j.tetlet.2005.08.137,2005-09-15,0.7240642786185283
Tetrahedron,Stereocontrol in the synthesis of kainoids,,10.1016/0040-4039(96)01522-5,1996-09-01,0.7240642786185283
Tetrahedron,Synthesis of axinastatins 2 – 5,,10.1016/0040-4039(96)01105-7,1996-07-01,0.7240642786185283
Synthesis,Synthesis of Adamantylideneadamantane,,10.1055/s-1970-21658,1970-01-01,0.7240642786185283
Tetrahedron,Synthesis of diselenides and selenides from elemental selenium,,10.1016/s0040-4039(02)00277-0,2002-04-01,0.7240642786185283
Tetrahedron,Synthesis of isocoumarins and α-pyrones via iodocyclization,,10.1016/s0040-4039(02)01731-8,2002-10-01,0.7240642786185283
Tetrahedron,"First synthesis of S,S-dialkyl difluorophosphonodithioates and difluorophosphonotrithioates",,10.1016/j.tetlet.2003.09.195,2003-11-07,0.7240642786185283
Synthesis,"Synthesis of α,β-Unsaturated Imidates",,10.1055/s-1982-29717,1982-01-01,0.7240642786185283
Synthesis,"Synthesis of Pyrazolo[3,4-<i>g</i>][2,1]benzisoxazoles",,10.1055/s-1982-29899,1982-01-01,0.7240642786185283
Synthesis,Synthesis of Phospholiponucleosides,,10.1055/s-1982-29813,1982-01-01,0.7240642786185283
Synthesis,The Synthesis of C-6′-Methylthiamin and C-6′-Ethylthiamin,,10.1055/s-1983-30422,1983-01-01,0.7240642786185283
Synthesis,A Synthesis of<i>m</i>-Terphenyls,,10.1055/s-1983-30384,1983-01-01,0.7240642786185283
Synthesis,Hexadecarboxylative Synthesis of Hexaazatriphenylene,,10.1055/s-1988-27470,1988-01-01,0.7240642786185283
Synthesis,Chlorovinylcarbenoid: Synthesis of<i>gem</i>-Chlorovinylcyclopropanes,,10.1055/s-1979-28701,1979-01-01,0.7240642786185283
Tetrahedron,"N-Bromosuccinimide-dimercaptoethane cobromination of alkenes: synthesis of β,β′-dibromodithioethers",,10.1016/s0040-4039(03)01221-8,2003-06-30,0.7240642786185283
Tetrahedron,C2-Acetamidomannosylation. Synthesis of 2-N-acetylamino-2-deoxy-α-d-mannopyranosides with glucal donors,,10.1016/s0040-4039(03)00871-2,2003-05-01,0.7240642786185283
Tetrahedron,Synthesis and two-photon absorption property of phenylacetylene macrocycles,,10.1016/s0040-4039(03)01261-9,2003-06-30,0.7240642786185283
Tetrahedron,Synthesis of (+)-totarol,,10.1016/j.tetlet.2003.09.193,2003-11-07,0.7240642786185283
Tetrahedron,"Synthesis of 4-arylidenecyclohexane-1,3-diones from the Baylis–Hillman acetates",,10.1016/s0040-4039(03)00397-6,2003-03-01,0.7240642786185283
Tetrahedron,A synthesis of crambescidin 359,,10.1016/s0040-4039(02)02531-5,2003-01-01,0.7240642786185283
Tetrahedron,Synthesis of some halogenated tetraarylborates,,10.1016/s0040-4039(03)01881-1,2003-09-12,0.7240642786185283
Tetrahedron,Synthesis of ferrocenyl quinones,,10.1016/s0040-4039(03)00099-6,2003-03-01,0.7240642786185283
Tetrahedron,Synthesis of a deep-cavity thiacalix[4]arene,,10.1016/j.tetlet.2003.09.048,2003-10-01,0.7240642786185283
Tetrahedron,Synthesis of (±)-solanapyrones A and B,,10.1016/s0040-4039(03)00288-0,2003-03-01,0.7240642786185283
Synthesis,"Synthesis of 2,5-Diarylfurans from Phenacyl Bromides",,10.1055/s-1984-30904,1984-01-01,0.7240642786185283
Synthesis,Synthesis of Diisopropyl 1-Nitroalkanephosphonates from Diisopropyl 1-Oxoalkanephosphonates,,10.1055/s-1984-30924,1984-01-01,0.7240642786185283
Tetrahedron,Synthesis and two-photon absorption of triphenylbenzene-cored dendritic chromophores,,10.1016/s0040-4039(03)00455-6,2003-03-01,0.7240642786185283
Tetrahedron,Corrigendum to “Synthesis of phosphocarnitine”,,10.1016/s0040-4039(02)00436-7,2002-04-01,0.7240642786185283
Tetrahedron,"The synthesis of 3,3,4,4-tetraphenyl-2-butanone from 1,1-diphenylacetone",,10.1016/s0040-4039(02)00861-4,2002-07-01,0.7240642786185283
Tetrahedron,Synthesis of variolin B,,10.1016/s0040-4039(03)01551-x,2003-07-31,0.7240642786185283
Tetrahedron,Semi-synthesis of neomangiferin from mangiferin,,10.1016/j.tetlet.2014.03.129,2014-04-05,0.7240642786185283
Tetrahedron,A biomimetic synthesis of coelenterazine analogs,,10.1016/s0040-4039(02)00462-8,2002-04-01,0.7240642786185283
Tetrahedron,"An expeditious synthesis of a (3S,4S,5R)-trihydroxyazepane",,10.1016/s0040-4039(03)01870-7,2003-09-01,0.7240642786185283
Tetrahedron,First synthesis of adamantylated thiacalix[4]arenes,,10.1016/s0040-4039(02)00977-2,2002-07-01,0.7240642786185283
Tetrahedron,Synthesis of N-alkoxybenzimidazoles and N-alkoxypyrimidazoles,,10.1016/s0040-4039(02)01841-5,2002-10-01,0.7240642786185283
Tetrahedron,The synthesis of (±)-gelsemine,,10.1016/s0040-4039(01)02213-4,2002-01-01,0.7240642786185283
Tetrahedron,Synthesis of the napalilactone and pathylactone A spirocyclic skeleton,,10.1016/s0040-4039(01)02141-4,2002-01-01,0.7240642786185283
Synthesis,Synthesis of Dialkyl 2-(Dialkoxyphosphinyloxy)-alkanephosphonates,,10.1055/s-1984-30858,1984-01-01,0.7240642786185283
Tetrahedron,Synthesis of octyl glucopyranoside by almond β-glucosidase adsorbed onto Celite R-640®,,10.1016/s0040-4039(02)00197-1,2002-03-01,0.7240642786185283
Tetrahedron,Synthesis and recognition behaviour of allosteric hemicarcerands,,10.1016/s0040-4039(02)00086-2,2002-03-01,0.7240642786185283
Tetrahedron,Synthesis of dibromophakellstatin and dibromoisophakellin,,10.1016/s0040-4039(02)00966-8,2002-07-01,0.7240642786185283
Tetrahedron,Synthesis of phenanthrenes from formylbenzoquinone,,10.1016/s0040-4039(02)01026-2,2002-07-01,0.7240642786185283
Tetrahedron,First enantiospecific synthesis of (−)-9-pupukeanone,,10.1016/s0040-4039(01)02336-x,2002-02-01,0.7240642786185283
Tetrahedron,"Synthesis of 1,1-dibromo-1-alkenes from partially and unprotected aldoses",,10.1016/s0040-4039(02)00149-1,2002-03-01,0.7240642786185283
Tetrahedron,Bidirectional synthesis of montamine analogs,,10.1016/j.tetlet.2013.07.134,2013-08-02,0.7240642786185283
Tetrahedron,Synthesis of 2-pyrone-4-carboxaldehydes from acetylene dicarboxaldehyde monoacetal,,10.1016/j.tetlet.2004.10.081,2004-11-04,0.7240642786185283
Tetrahedron,"Synthesis of hydroxylated hexahydropyrrolo[2,1-b]thiazoles",,10.1016/j.tetlet.2004.01.016,2004-01-27,0.7240642786185283
Tetrahedron,Synthesis of l-aminohomohistidine (l-Ahh),,10.1016/j.tetlet.2004.02.027,2004-02-27,0.7240642786185283
Tetrahedron,Synthesis of (+)- and (−)-isocarvone,,10.1016/j.tetlet.2004.04.181,2004-05-29,0.7240642786185283
Tetrahedron,Synthesis of (±)-cartorimine,,10.1016/j.tetlet.2004.12.007,2004-12-19,0.7240642786185283
Tetrahedron,"Iridodials: enantiospecific synthesis and stereochemical assignment of the pheromone for the golden-eyed lacewing, Chrysopa oculata",,10.1016/j.tetlet.2004.03.034,2004-03-28,0.7240642786185283
Tetrahedron,"Synthesis of 1,1-diarylethylenes from an α-stannyl β-silylstyrene",,10.1016/j.tetlet.2003.12.106,2004-01-17,0.7240642786185283
Tetrahedron,A synthesis of the tetracyclic carboskeleton of isaindigotidione,,10.1016/j.tetlet.2004.02.052,2004-02-28,0.7240642786185283
Tetrahedron,"Synthesis of 2,3′-biindolyls and indolo[3,2-a]carbazoles",,10.1016/j.tetlet.2004.08.024,2004-08-25,0.7240642786185283
Tetrahedron,"Synthesis of heliannuol D, an allelochemical from Helianthus annus",,10.1016/j.tetlet.2003.11.098,2003-12-10,0.7240642786185283
Tetrahedron,Synthesis of the C1–C27 portion of the aplyronines,,10.1016/j.tetlet.2004.04.159,2004-05-29,0.7240642786185283
Tetrahedron,Stereocontrolled synthesis of quinine and quinidine,,10.1016/j.tetlet.2004.03.085,2004-04-19,0.7240642786185283
Tetrahedron,Synthesis of dihydroxylated polyamines from an erythronolactone,,10.1016/s0040-4039(03)00693-2,2003-04-01,0.7240642786185283
Tetrahedron,"Synthesis of (15S,16S,21R)-4-deoxyrollicosin analog",,10.1016/j.tetlet.2003.08.088,2003-09-22,0.7240642786185283
Tetrahedron,Synthesis of coumermycin A1,,10.1016/s0040-4039(02)02487-5,2003-01-01,0.7240642786185283
Tetrahedron,Synthesis of copolymers alternating oligophenylenevinylene subunits and fullerene moieties,,10.1016/s0040-4039(03)00991-2,2003-05-19,0.7240642786185283
Tetrahedron,A synthesis of camptothecin,,10.1016/j.tetlet.2004.02.091,2004-03-19,0.7240642786185283
Tetrahedron,Fluorous thiols in oligosaccharide synthesis,,10.1016/j.tetlet.2004.04.116,2004-05-11,0.7240642786185283
Tetrahedron,First synthesis of antimalarial Machaeriols A and B,,10.1016/j.tetlet.2003.12.107,2004-01-17,0.7240642786185283
Tetrahedron,"Synthesis of benz[5,6]azepino[4,3-b]indoles by 1,7-electrocyclisation of azomethine ylides",,10.1016/j.tetlet.2004.11.127,2004-12-09,0.7240642786185283
Tetrahedron,Synthesis of 7-oxa-phomopsolide E and its C-4 epimer,,10.1016/j.tetlet.2003.11.089,2003-12-12,0.7240642786185283
Tetrahedron,Synthesis of (+)-prelactone B,,10.1016/s0040-4039(03)00326-5,2003-03-01,0.7240642786185283
Tetrahedron,Synthesis of oligoenynes and oligomeric conjugated diacetylenes,,10.1016/s0040-4039(02)02777-6,2003-01-01,0.7240642786185283
Tetrahedron,Synthesis of α- and β-C-glycosides of N-acetylglucosamine,,10.1016/s0040-4039(03)00818-9,2003-04-25,0.7240642786185283
Tetrahedron,"Enantiospecific synthesis of [7R,6S,5S,4R]-triacetoxy-(−)-goniotriol",,10.1016/s0040-4039(02)01048-1,2002-07-01,0.7240642786185283
Tetrahedron,Synthesis of anhydro psicofuranosyl nucleosides,,10.1016/s0040-4039(02)01472-7,2002-09-01,0.7240642786185283
Tetrahedron,"Synthesis of 2,5-dihalothiazole-4-carboxylates",,10.1016/s0040-4039(02)01556-3,2002-09-01,0.7240642786185283
Tetrahedron,"Synthesis of caged myo-inositol 1,3,4,5-tetrakisphosphate",,10.1016/s0040-4039(02)02834-4,2003-02-01,0.7240642786185283
Tetrahedron,"First synthesis of 1,9-dideoxyforskolin from ptychantin A",,10.1016/s0040-4039(03)00236-3,2003-03-01,0.7240642786185283
Tetrahedron,"First synthesis of (1,2-13C2)-monolignol glucosides",,10.1016/j.tetlet.2004.09.126,2004-10-07,0.7240642786185283
Tetrahedron,"Enantiospecific synthesis of an indolizidine alkaloid, (+)-ipalbidine",,10.1016/s0040-4039(03)00563-x,2003-03-25,0.7240642786185283
Tetrahedron,Synthesis of agarofuran antifeedants. Part 3: Synthesis of polyhydroxylated pyrano-agarofurans,,10.1016/s0040-4039(02)02027-0,2002-11-01,0.7240642786185283
Tetrahedron,Synthesis of the C(1)–C(8) segment of (+)-acutiphycin,,10.1016/s0040-4039(01)02383-8,2002-02-01,0.7240642786185283
Tetrahedron,Synthesis of a salbutamol dimer,,10.1016/s0040-4039(01)02354-1,2002-02-01,0.7240642786185283
Tetrahedron,Synthesis of montiporynes A and B,,10.1016/s0040-4039(01)02143-8,2002-01-01,0.7240642786185283
Tetrahedron,The surprise synthesis of α-GlcNAc 1-C-sulfonates,,10.1016/s0040-4039(02)01218-2,2002-08-01,0.7240642786185283
Tetrahedron,Synthesis of conformationally constrained β-turn thiazolidine mimetic,,10.1016/s0040-4039(01)02357-7,2002-02-01,0.7240642786185283
Tetrahedron,"Synthesis of a multitopic pyrene–thiophene–anthracene-2,2′:6′,2″-terpyridine array",,10.1016/j.tetlet.2004.02.019,2004-03-01,0.7240642786185283
Tetrahedron,Synthesis of (+)-agelasine D from (+)-manool,,10.1016/j.tetlet.2004.04.030,2004-04-29,0.7240642786185283
Tetrahedron,Synthesis of Cinacalcet congeners,,10.1016/j.tetlet.2004.09.063,2004-09-28,0.7240642786185283
Tetrahedron,Synthesis of tryptophan N -glucoside,,10.1016/j.tetlet.2003.10.190,2003-11-21,0.7240642786185283
Tetrahedron,Synthesis of lipidic tamoxifen,,10.1016/s0040-4039(00)00421-4,2000-04-01,0.7240642786185283
Synthesis,Synthesis of Glycosides of Nicotinamide and Nicotinamide Mononucleotide,,10.1055/s-1981-29462,1981-01-01,0.7240642786185283
Tetrahedron,"Synthesis of indazole- N -oxides via the 1,7-electrocyclisation of azomethine ylides",,10.1016/s0040-4039(01)00892-9,2001-07-01,0.7240642786185283
Tetrahedron,"Synthesis of naphthopyrrolo[3,4-c]carbazoles",,10.1016/s0040-4039(01)01308-9,2001-10-01,0.7240642786185283
Synthesis,"Synthesis of Hexahydro[1,3]thiazolo[3,2-<i>a</i>]pyridines (7-Thia-1-azabicyclo[4.3.0]nonanes)",,10.1055/s-1980-29030,1980-01-01,0.7240642786185283
Synthesis,"Synthesis of 2,4-Benzodiazepines from Phthalimide Mannich Bases",,10.1055/s-1980-29038,1980-01-01,0.7240642786185283
Synthesis,Synthesis of 4-Arylbutanenitriles,,10.1055/s-1981-29334,1981-01-01,0.7240642786185283
Synthesis,"Synthesis of 1,4,5,8-Tetraazaphenanthrene",,10.1055/s-1980-28936,1980-01-01,0.7240642786185283
Synthesis,"Synthesis of 2-Phenoxy-2,2′(3<i>H</i>,3′<i>H</i>)-spirobi[1,3,2-benzoxazaphosphole]",,10.1055/s-1980-29298,1980-01-01,0.7240642786185283
Synthesis,"Condensed Heterocycles; Part XII. Synthesis of [1,2,5]Thiadiazolo[3,4-<i>c</i>]quinolines and [1,2,5]Selenadiazolo[3,4-<i>c</i>]quinolines",,10.1055/s-1983-30436,1983-01-01,0.7240642786185283
Tetrahedron,Synthesis of fluorescence labeled sialyl LewisX glycosphingolipids,,10.1016/s0040-4039(00)01995-x,2001-01-01,0.7240642786185283
Tetrahedron,Strategic innovations for the synthesis of vinigrol,,10.1016/j.tetlet.2018.05.049,2018-05-19,0.7240642786185283
Tetrahedron,Synthesis of (+)-piclavines A1 and A2,,10.1016/s0040-4039(00)00868-6,2000-07-01,0.7240642786185283
Tetrahedron,First synthesis of a selenazepane,,10.1016/j.tetlet.2005.07.127,2005-08-16,0.7240642786185283
Tetrahedron,The first stereocontrolled synthesis of isoflavanones,,10.1016/s0040-4039(00)01464-7,2000-10-01,0.7240642786185283
Tetrahedron,Synthesis of morphine 6-α-d-glucuronide,,10.1016/s0040-4039(00)01111-4,2000-08-01,0.7240642786185283
Tetrahedron,Synthesis of picropodophyllin homolactone,,10.1016/s0040-4039(00)01136-9,2000-08-01,0.7240642786185283
Synthesis,Synthesis of 3-Iodoflavans and 2<i>H</i>-Flavenes,,10.1055/s-1980-29139,1980-01-01,0.7240642786185283
Synthesis,"Condensed Heterocycles; Xl. Synthesis of 1,2,5-Thia(selena)diazolo[3,4-<i>b</i>]quinolines and 1,2,5-Thia(selena)diazolo[3,4-<i>h</i>]quinolines",,10.1055/s-1981-29435,1981-01-01,0.7240642786185283
Synthesis,"Synthesis of 1,4-Cyclohexanediones by Photocycloaddition",,10.1055/s-1980-29309,1980-01-01,0.7240642786185283
Synthesis,Synthesis of Selenolcarbamates,,10.1055/s-1979-28772,1979-01-01,0.7240642786185283
Synthesis,"Synthesis of<i>N</i>,<i>N</i>-Dialkyl-3-oxoalkanamides",,10.1055/s-1979-28886,1979-01-01,0.7240642786185283
Tetrahedron,Synthesis of a tetracyclic 2′-deoxyadenosine analog,,10.1016/s0040-4039(99)01875-4,1999-12-01,0.7240642786185283
Tetrahedron,The synthesis of the C15–C24 segment of Ratjadone,,10.1016/s0040-4039(99)01486-0,1999-10-01,0.7240642786185283
Journal of Organic Chemistry,Synthesis of α-Hydroxyacetophenones,,,2012-01-01,0.7240642786185283
Synthesis,Synthesis of Vicinal Iodoselenocyanates,,10.1055/s-1978-24699,1978-01-01,0.7240642786185283
Tetrahedron,"Synthesis of (−)-(1S,5R)- and (+)-(1R,5S)-trifluoroanalogues of frontalin",,10.1016/s0040-4039(99)01186-7,1999-08-01,0.7240642786185283
Tetrahedron,Synthesis of marine sesterterpenoid dysidiolide,,10.1016/s0040-4039(99)02175-9,2000-02-01,0.7240642786185283
Tetrahedron,Synthesis of salacinol,,10.1016/s0040-4039(00)01129-1,2000-08-01,0.7240642786185283
Tetrahedron,Synthesis of the isocoumarin portion of the rubromycins,,10.1016/s0040-4039(01)00524-x,2001-05-01,0.7240642786185283
Synthesis,Synthesis of 1-Aminoalkanephosphonates via Thioureidoalkanephosphonates,,10.1055/s-1978-24787,1978-01-01,0.7240642786185283
Tetrahedron,Synthesis of the fucosylated biantennary N-glycan of erythropoietin,,10.1016/j.tetlet.2006.05.086,2006-06-20,0.7240642786185283
Tetrahedron,"Synthesis of 1,2,3,4-tetrahydroascididemin",,10.1016/s0040-4039(99)00690-5,1999-05-01,0.7240642786185283
Tetrahedron,Synthesis of the tangutorine skeleton,,10.1016/s0040-4039(99)01474-4,1999-09-01,0.7240642786185283
Tetrahedron,Synthesis of glycosyl phosphates from acetylated glycosyl nitrates,,10.1016/s0040-4039(99)00698-x,1999-05-01,0.7240642786185283
Tetrahedron,Synthesis of glycosyl strapped porphyrins,,10.1016/s0040-4039(99)00259-2,1999-03-01,0.7240642786185283
Tetrahedron,Synthesis of the phosphodisaccharide repeat of antigenic lipophosphoglycan of Leishmania donovani parasite,,10.1016/s0040-4039(99)00231-2,1999-03-01,0.7240642786185283
Tetrahedron,Enantiospecific synthesis of 8-epipuupehedione from ( R )-(−)-carvone,,10.1016/s0040-4039(01)00153-8,2001-03-01,0.7240642786185283
Tetrahedron,"Synthesis of 1,3-diaryl benzo[c]thiophenes",,10.1016/j.tetlet.2005.04.048,2005-05-06,0.7240642786185283
Tetrahedron,"Synthesis of isomeric 1,4-[13C]2-labeled 2-ethoxycarbonyl-1,4-diphenylbutadienes",,10.1016/s0040-4039(00)02021-9,2001-01-01,0.7240642786185283
Synthesis,Synthesis of α-Iminonitriles (Imidoyl Cyanides),,10.1055/s-1978-24930,1978-01-01,0.7240642786185283
Tetrahedron,Synthesis of macrosphelides H and G,,10.1016/s0040-4039(02)00781-5,2002-06-01,0.7240642786185283
Tetrahedron,Synthesis of photoresponsive polyamidoamine (PAMAM) dendritic architecture,,10.1016/s0040-4039(00)01996-1,2001-01-01,0.7240642786185283
Tetrahedron,Synthesis of β-sulfinyl nitroxides,,10.1016/s0040-4039(01)02012-3,2001-12-01,0.7240642786185283
Tetrahedron,First synthesis of segetalin A and analogous cyclohexapeptides,,10.1016/s0040-4039(00)02354-6,2001-02-01,0.7240642786185283
Angewandte Chemie International Edition,-Mannosynthase: Synthesis of -Mannosides with a Mutant -Mannosidase,,10.1002/1521-3773(20010119)40:2<417::aid-anie417>3.3.co;2-m,2001-01-19,0.7240642786185283
Synthesis,Synthesis of (±)-Decan-9-olide (Phoracantholide I) from Cyclohexanone,,10.1055/s-1981-29331,1981-01-01,0.7240642786185283
Synthesis,Synthesis of<i>N</i>-Acylated 1-Aminoalkyl-diphenylphosphine Oxides by Amidoalkylation of Diphenylchlorophosphine,,10.1055/s-1981-29475,1981-01-01,0.7240642786185283
Synthesis,"Synthesis of 3,4-Diphenylpyrroles via<i>C</i>-Benzylnitrone Cyclodimers",,10.1055/s-1981-29529,1981-01-01,0.7240642786185283
Synthesis,"Synthesis of 5-(Arylmethylene)-2-piperidino(or morpholino)-2,4-diphenyl-3-thiazolines",,10.1055/s-1981-29436,1981-01-01,0.7240642786185283
Synthesis,"Synthesis of 1,4-Diaryl-2,3-diformylbutadienes",,10.1055/s-1980-29259,1980-01-01,0.7240642786185283
Tetrahedron,A biogenetically patterned enantiospecific synthesis of allopupukeanones,,10.1016/j.tetlet.2005.11.009,2005-11-18,0.7240642786185283
Tetrahedron,A synthesis of FR901464,,10.1016/s0040-4039(01)01763-4,2001-11-01,0.7240642786185283
Tetrahedron,Synthesis of deoxyvariolin B,,10.1016/s0040-4039(00)01916-x,2001-01-01,0.7240642786185283
Tetrahedron,Synthesis of fullerene–cyclodextrin conjugates,,10.1016/s0040-4039(01)01375-2,2001-09-01,0.7240642786185283
Tetrahedron,"Synthesis of unsymmetrical 4,6-diarylpyrimidines",,10.1016/j.tetlet.2005.04.043,2005-04-28,0.7240642786185283
Tetrahedron,Formal synthesis of (+)-isolaurepinnacin,,10.1016/s0040-4039(00)01880-3,2001-01-01,0.7240642786185283
Tetrahedron,Stereocontrolled synthesis of 2-alkenyl-4-methylene tetrahydropyrans,,10.1016/j.tetlet.2004.07.063,2004-08-17,0.7240642786185283
Tetrahedron,Stereocontrolled synthesis of 5-(1′-hydroxyalkyl)-3-methylidenetetrahydro-2-furanones,,10.1016/s0040-4039(01)00316-1,2001-04-01,0.7240642786185283
Synthesis,Synthesis of 2-(2-Arylethyl)-indoles,,10.1055/s-1985-31150,1985-01-01,0.7240642786185283
Synthesis,"Synthesis of 6<i>H</i>-Dibenzo[<i>b,f</i>]-oxocin",,10.1055/s-1981-29379,1981-01-01,0.7240642786185283
Tetrahedron,"Synthesis of 1,3-diarylbenzo[c]selenophenes",,10.1016/j.tetlet.2005.08.069,2005-09-03,0.7240642786185283
Tetrahedron,Toward the synthesis of pamamycin-607,,10.1016/s0040-4039(00)00022-8,2000-03-01,0.7240642786185283
Tetrahedron,Formal synthesis of (±)-cladoniamide G,,10.1016/j.tetlet.2014.01.086,2014-01-27,0.7240642786185283
Tetrahedron,Synthesis of (±)-desamino huperzine A,,10.1016/s0040-4039(00)01670-1,2000-11-01,0.7240642786185283
Tetrahedron,Synthesis of nitrocyclopropyl peptidomimetics,,10.1016/j.tetlet.2013.09.106,2013-09-27,0.7240642786185283
Tetrahedron,Synthesis of the spiroacetal parts of spirofungin A and B,,10.1016/s0040-4039(00)00371-3,2000-04-01,0.7240642786185283
Tetrahedron,The synthesis of the glucuronide adduct of Trocade™,,10.1016/s0040-4039(00)01556-2,2000-11-01,0.7240642786185283
Tetrahedron,Synthesis of fullerene–oligophenyleneethynylene hybrids,,10.1016/s0040-4039(01)00384-7,2001-04-01,0.7240642786185283
Tetrahedron,Synthesis of tetrakis(2-thienyl)methane,,10.1016/s0040-4039(02)00408-2,2002-04-01,0.7240642786185283
Tetrahedron,"Synthesis of (2S,3S)-β-methyltryptophan",,10.1016/s0040-4039(01)00718-3,2001-07-01,0.7240642786185283
Tetrahedron,Synthesis of (+)-hernandulcin and (+)-epihernandulcin,,10.1016/s0040-4039(02)00939-5,2002-07-01,0.7240642786185283
Tetrahedron,Enantiospecific synthesis of (+)-herbertene,,10.1016/s0040-4039(01)02365-6,2002-02-01,0.7240642786185283
Tetrahedron,A synthesis of aziridines from α-iodoenones,,10.1016/s0040-4039(02)00791-8,2002-06-01,0.7240642786185283
Tetrahedron,Synthesis of quercetin 3-O-(2′′-galloyl)-α-l-arabinopyranoside,,10.1016/s0040-4039(02)02139-1,2002-12-01,0.7240642786185283
Tetrahedron,Corrigendum to “Enantiospecific synthesis of 8-epipuupehedione from (R)-(−)-carvone”,,10.1016/s0040-4039(01)00523-8,2001-05-01,0.7240642786185283
Synthesis,"An Elegant Synthesis of 2,2-Dimethylchromans",,10.1055/s-1981-29510,1981-01-01,0.7240642786185283
Synthesis,The Synthesis of Triazines from<i>N</i>-Cyanocarbamimidates,,10.1055/s-1981-29645,1981-01-01,0.7240642786185283
Synthesis,Thiations with Tetraphosphorus Decasulfide in Hexamethylphosphoric Triamide; Synthesis of Thioacronycine and Acridanethiones,,10.1055/s-1982-29851,1982-01-01,0.7240642786185283
Tetrahedron,"Synthesis of (+)-testudinariol A, a triterpene metabolite of the marine mollusc Pleurobrancus testudinarius",,10.1016/s0040-4039(00)02179-1,2001-02-01,0.7240642786185283
Tetrahedron,The synthesis of 3-diazo-2-nitromethylenepiperidine,,10.1016/s0040-4039(00)02323-6,2001-02-01,0.7240642786185283
Tetrahedron,Synthesis of (±)-7-episordidin,,10.1016/s0040-4039(01)02261-4,2002-01-01,0.7240642786185283
Tetrahedron,The synthesis of D-chalcose,,10.1016/s0040-4039(01)90664-1,1963-01-01,0.7240642786185283
Tetrahedron,Synthesis of diphenylarsenonitride tetramer,,10.1016/s0040-4039(00)70485-0,1962-01-01,0.7240642786185283
Tetrahedron,Synthesis of D-norprogesterone,,10.1016/s0040-4039(00)70514-4,1962-01-01,0.7240642786185283
Tetrahedron,The synthesis of pachyrrhizin,,10.1016/s0040-4039(01)99482-1,1959-01-01,0.7240642786185283
Tetrahedron,Electroorganic synthesis of benzathine,,10.1016/j.tetlet.2006.11.008,2006-11-22,0.7240642786185283
Tetrahedron,Enantiospecific synthesis of (−)-d-noviose from (−)-pantolactone,,10.1016/j.tetlet.2006.06.172,2006-08-07,0.7240642786185283
Tetrahedron,Aromaticity in azlactone anions and its significance for the Erlenmeyer synthesis,,10.1016/j.tetlet.2006.06.006,2006-06-22,0.7240642786185283
Tetrahedron,Synthesis of spiroannulated dihydroisobenzofuranylated monosaccharides,,10.1016/j.tetlet.2006.03.016,2006-03-25,0.7240642786185283
Tetrahedron,The synthesis of isocamphorquinone,,10.1016/s0040-4039(00)70949-x,1962-01-01,0.7240642786185283
Tetrahedron,Synthesis of azasugars. Part 2 isomerization of polyhydroxylated azepanes,,10.1016/0040-4039(96)00097-4,1996-03-01,0.7240642786185283
Tetrahedron,The synthesis of euparin and dehydrotremetone,,10.1016/s0040-4039(01)90741-5,1963-01-01,0.7240642786185283
Tetrahedron,The synthesis of orotidine,,10.1016/s0040-4039(01)90668-9,1963-01-01,0.7240642786185283
Tetrahedron,"Synthesis of pratensein, 5,7,3′-trihydroxy-4′-methoxyisoflavone",,10.1016/s0040-4039(01)90597-0,1963-01-01,0.7240642786185283
Tetrahedron,First synthesis of indirubin N-glycosides (red sugars),,10.1016/j.tetlet.2006.07.024,2006-08-07,0.7240642786185283
Tetrahedron,The synthesis of circumanthracene,,10.1016/s0040-4039(00)92350-5,1991-09-01,0.7240642786185283
Tetrahedron,Biogenetically patterned synthesis of cadambine,,10.1016/0040-4039(91)85020-6,1991-04-01,0.7240642786185283
Tetrahedron,Face-to-face metallocenes. The synthesis of a cymantrene-ferrocene triad.,,10.1016/s0040-4039(00)97782-7,1990-01-01,0.7240642786185283
Tetrahedron,Synthesis of partially hydrogenated BINAP variants,,10.1016/0040-4039(91)80499-v,1991-12-01,0.7240642786185283
Tetrahedron,"Synthesis of (±)-5,6,7-trinor-4,8-inter--phenylene PGI2",,10.1016/s0040-4039(00)97656-1,1990-01-01,0.7240642786185283
Tetrahedron,Synthesis of tachysterol,,10.1016/s0040-4039(01)90843-3,1963-01-01,0.7240642786185283
Tetrahedron,Steroids—CXXI synthesis of halogenated steroid hormones,,10.1016/s0040-4039(01)82756-8,1959-01-01,0.7240642786185283
Tetrahedron,A synthesis of α-anhydrotrimethylbrazilone,,10.1016/s0040-4039(01)82711-8,1959-01-01,0.7240642786185283
Tetrahedron,Steroids—CXX synthesis of halogenated steroid hormones,,10.1016/s0040-4039(01)82755-6,1959-01-01,0.7240642786185283
Tetrahedron,SYNTHESIS OF THE THIENOTROPYLIUM CATION,,10.1016/b978-1-4831-9886-6.50085-1,1963-01-01,0.7240642786185283
Tetrahedron,"SYNTHESIS OF PRATENSEIN, 5,7,3' -TRIHYDROXY-4'-MBTHOXYISOFLAVONE",,10.1016/b978-1-4831-9886-6.50036-x,1963-01-01,0.7240642786185283
Tetrahedron,First synthesis of pentacoordinated phosphirenes,,10.1016/s0040-4039(00)97414-8,1990-01-01,0.7240642786185283
Tetrahedron,Synthesis of carbocyclic clitocine,,10.1016/s0040-4039(00)94392-2,1990-01-01,0.7240642786185283
Tetrahedron,Diastereospecific synthesis of (−)-statine,,10.1016/s0040-4039(00)88557-3,1990-01-01,0.7240642786185283
Tetrahedron,Synthesis of (±)- psicoplanocin A.,,10.1016/s0040-4039(00)98007-9,1990-01-01,0.7240642786185283
Tetrahedron,Synthesis of the thienotropylium cation,,10.1016/s0040-4039(01)90646-x,1963-01-01,0.7240642786185283
Tetrahedron,Synthesis and characterisation of polymerisable photochromic spiropyrans: towards photomechanical biomaterials,,10.1016/j.tetlet.2006.11.110,2006-12-09,0.7240642786185283
Tetrahedron,"The synthesis of heliannuol C, an allelochemical from Helianthus annuus",,10.1016/j.tetlet.2006.04.011,2006-05-05,0.7240642786185283
Tetrahedron,"The synthesis of benzannulated spiroketals from 1,1-diacyl-2-phenylcyclopropanes",,10.1016/j.tetlet.2021.152984,2021-03-18,0.7240642786185283
Tetrahedron,The synthesis of Digicitrin,,10.1016/s0040-4039(01)89064-x,1965-01-01,0.7240642786185283
Tetrahedron,Synthesis of diacetyldeuteroporphyrin IX,,10.1016/s0040-4039(01)99591-7,1965-01-01,0.7240642786185283
Tetrahedron,Synthesis of the tricyclic skeleton of Daphniphyllum alkaloids daphnimacropodines,,10.1016/j.tetlet.2021.153030,2021-03-27,0.7240642786185283
Tetrahedron,"Synthesis of Gymnasterone B, an antitumor steroid from Gymnascella dankaliensis",,10.1016/j.tetlet.2006.03.072,2006-04-01,0.7240642786185283
Tetrahedron,Synthesis of C-1 spirocyclopropyl sugars from anomeric diazides.,,10.1016/s0040-4039(00)97642-1,1990-01-01,0.7240642786185283
Tetrahedron,Synthesis of marine alkaloid ascididemin,,10.1016/s0040-4039(00)97626-3,1990-01-01,0.7240642786185283
Tetrahedron,First synthesis of carbocyclic oligothymidylates,,10.1016/s0040-4039(00)88833-4,1990-01-01,0.7240642786185283
Tetrahedron,Synthesis of per-6-guanidinylated cyclodextrins,,10.1016/j.tetlet.2005.11.124,2005-12-10,0.7240642786185283
Tetrahedron,Synthesis of (±)-α-chamigrene.,,10.1016/s0040-4039(00)74834-9,1991-01-01,0.7240642786185283
Tetrahedron,“Remote” dianions 5. Synthesis of δ-coniceine,,10.1016/s0040-4039(00)93425-7,1991-09-01,0.7240642786185283
Tetrahedron,Synthesis of the putative l-arginine metabolite L-NG-hydroxyarginine,,10.1016/s0040-4039(00)92109-9,1991-02-01,0.7240642786185283
Tetrahedron,Synthesis of the first tris(crown formazan),,10.1016/j.tetlet.2005.12.078,2006-01-10,0.7240642786185283
Tetrahedron,Synthesis of the sea anemone purine caissarone,,10.1016/s0040-4039(00)71228-7,1991-01-01,0.7240642786185283
Tetrahedron,Synthesis of tritium labeled KRN7000,,10.1016/j.tetlet.2006.03.131,2006-04-13,0.7240642786185283
Tetrahedron,"Synthesis of trishomohypostrophene, trishomohypostrophenone, trishomopentaprismane and trishomopentaprismanone",,10.1016/0040-4039(90)87017-t,1990-01-01,0.7240642786185283
Tetrahedron,Synthesis of (−)-gloeosporone,,10.1016/s0040-4039(00)79490-1,1991-01-01,0.7240642786185283
Tetrahedron,"Synthesis and conformation of 2-dimethoxyphosphoryl-1,3-diselenanes. The first evidence for SeCP anomeric interactions.",,10.1016/s0040-4039(00)79901-1,1991-08-01,0.7240642786185283
Tetrahedron,"Synthesis of (+)-5,6,7-trinor-4,8-inter--phenylene PGI2",,10.1016/s0040-4039(00)97657-3,1990-01-01,0.7240642786185283
Tetrahedron,The synthesis of 5′-deoxyjuglomycin A and 5′-methoxyjuglomycin A.,,10.1016/0040-4039(91)80184-8,1991-10-01,0.7240642786185283
Tetrahedron,Synthesis of (−)-δ-N-normethylskytanthine,,10.1016/0040-4039(91)80484-n,1991-12-01,0.7240642786185283
Tetrahedron,A formal synthesis of (±)-Ambrox®,,10.1016/s0040-4039(00)79879-0,1991-08-01,0.7240642786185283
Tetrahedron,A synthesis of (+)-7-Epiaustraline and (−)-7-Epialexine,,10.1016/0040-4039(91)80071-d,1991-09-01,0.7240642786185283
Tetrahedron,2-Benzothiazolylchloromethyllithium: Synthesis of oxiranes,,10.1016/s0040-4039(00)74787-3,1992-12-01,0.7240642786185283
Tetrahedron,Formal synthesis of dysiherbaine,,10.1016/j.tetlet.2013.10.038,2013-10-16,0.7240642786185283
Tetrahedron,"Synthesis of 4-(3,5-dialkyl-4-hydroxyphenyl)pyridines.",,10.1016/s0040-4039(00)61235-2,1992-08-01,0.7240642786185283
Synthesis,Preface: The SYNTHESIS–SYNLETT Lectureship,,10.1055/s-0036-1589531,2018-03-01,0.7240642786185283
Tetrahedron,Synthesis of a putative ddhCTP metabolite ddhC-homocysteine,,10.1016/j.tetlet.2023.154423,2023-02-26,0.7240642786185283
Tetrahedron,A biomimetic synthesis of calothrixin B,,10.1016/j.tetlet.2006.11.053,2006-11-30,0.7240642786185283
Tetrahedron,Synthesis of 6-azabenzo[a]pyrene,,10.1016/s0040-4039(00)97459-8,1990-01-01,0.7240642786185283
Tetrahedron,A synthesis of the oleanane skeleton,,10.1016/s0040-4039(00)70896-3,1962-01-01,0.7240642786185283
Tetrahedron,The synthesis of A-bisnorsteroids,,10.1016/s0040-4039(00)70427-8,1964-01-01,0.7240642786185283
Tetrahedron,Synthesis of 2-deoxystreptamine,,10.1016/s0040-4039(00)90415-5,1964-01-01,0.7240642786185283
Tetrahedron,An unambiguous synthesis of dihydrojacareubin,,10.1016/s0040-4039(00)90467-2,1964-01-01,0.7240642786185283
Tetrahedron,Synthesis of 7-methyltectorigenin,,10.1016/s0040-4039(00)90351-4,1964-01-01,0.7240642786185283
Tetrahedron,Synthesis of (−)-lapatin B,,10.1016/j.tetlet.2007.06.089,2007-06-26,0.7240642786185283
Tetrahedron,Hydroboration of C-arylglucals. Synthesis of the β-C-arylglucoside nucleus of chaetiacandin,,10.1016/s0040-4039(00)97006-0,1990-01-01,0.7240642786185283
Tetrahedron,Synthesis of phenoxyacetyl-N-(hydroxydioxocyclobutenyl)cycloserines,,10.1016/s0040-4039(00)79371-3,1991-07-01,0.7240642786185283
Tetrahedron,"Synthesis of the Janus integer pheromone (4R,9Z)-9-octadecen-4-olide",,10.1016/j.tetlet.2006.12.115,2006-12-26,0.7240642786185283
Angewandte Chemie International Edition,Synthesis of Hyperbranched Aminopolysaccharides,,10.1002/(sici)1521-3773(19980918)37:17<2373::aid-anie2373>3.3.co;2-2,1998-09-18,0.7240642786185283
Tetrahedron,Synthesis of a pentacovalent arsenic heterocycle,,10.1016/s0040-4039(00)71757-6,1961-01-01,0.7240642786185283
Tetrahedron,Synthesis of the thiapyrylium cation,,10.1016/s0040-4039(00)70271-1,1960-01-01,0.7240642786185283
Tetrahedron,Synthesis of a borepin,,10.1016/s0040-4039(01)82703-9,1960-01-01,0.7240642786185283
Tetrahedron,Synthesis of desmosine-KLH conjugated antigen via isoChichibabin pyridinium synthesis,,10.1016/j.tetlet.2023.154805,2023-10-20,0.7240642786185283
Tetrahedron,Synthesis of a Nor-Neolignan from Krameria Ramosissima,,10.1016/s0040-4039(00)79388-9,1991-07-01,0.7240642786185283
Tetrahedron,Towards a biomimetic synthesis of barrenazine A,,10.1016/j.tetlet.2007.04.108,2007-04-30,0.7240642786185283
Tetrahedron,The synthesis of an asparenomycin analog,,10.1016/s0040-4039(00)74477-7,1991-02-01,0.7240642786185283
Tetrahedron,Synthesis of ambracetal and epi-8-ambracetal,,10.1016/s0040-4039(00)74880-5,1991-02-01,0.7240642786185283
Tetrahedron,Synthesis of 3′-azido-5′-homothymidine analogs,,10.1016/s0040-4039(00)92706-0,1991-07-01,0.7240642786185283
Tetrahedron,Synthesis of the C8–C20 and C21–C30 segments of pectenotoxin 2,,10.1016/j.tetlet.2007.04.136,2007-05-02,0.7240642786185283
Tetrahedron,A synthesis of brefeldin A,,10.1016/s0040-4039(01)83130-0,1977-01-01,0.7240642786185283
Tetrahedron,A regiospecific synthesis of anthracyclinones,,10.1016/s0040-4039(01)83772-2,1977-01-01,0.7240642786185283
Tetrahedron,The synthesis of phosphoramidates from silylphosphites and azides,,10.1016/s0040-4039(01)92725-x,1977-01-01,0.7240642786185283
Tetrahedron,Synthesis of N-acetylmuramyl-L- [U−14C]alanyl-D-isoglutamine,,10.1016/s0040-4039(01)83425-0,1977-01-01,0.7240642786185283
Tetrahedron,"Synthesis of trifluoromethylated 1,4-diphosphanorbornadiene",,10.1016/s0040-4039(01)83156-7,1977-01-01,0.7240642786185283
Tetrahedron,Synthesis of the first perchloroarylacetylenes,,10.1016/s0040-4039(01)83762-x,1977-01-01,0.7240642786185283
Tetrahedron,First synthesis of (+)-myxothiazol A,,10.1016/j.tetlet.2008.09.125,2008-09-26,0.7240642786185283
Tetrahedron,The synthesis of 11a-carbathromboxane A2,,10.1016/s0040-4039(00)71428-6,1980-01-01,0.7240642786185283
Tetrahedron,Synthesis of polysaccharide α-(1–3)-L-rhamnan,,10.1016/s0040-4039(00)77416-8,1980-01-01,0.7240642786185283
Tetrahedron,A further synthesis of α-anhydrotrimethylbrazilone,,10.1016/s0040-4039(01)90912-8,1963-01-01,0.7240642786185283
Tetrahedron,A regiocontrolled synthesis of codonocarpine,,10.1016/s0040-4039(00)92847-8,1980-01-01,0.7240642786185283
Tetrahedron,Synthesis of N-benzoyl--ristosamine,,10.1016/0040-4039(80)88019-1,1980-01-01,0.7240642786185283
Tetrahedron,Synthesis of multifunctional hydroxyethyl tetrazoles,,10.1016/j.tetlet.2008.03.125,2008-03-31,0.7240642786185283
Tetrahedron,Synthesis of 5-alkynyl bicycloporphyrins as a synthon of 5-ethynyl bicycloporphyrin,,10.1016/j.tetlet.2021.152857,2021-02-02,0.7240642786185283
Tetrahedron,The synthesis of grandinol,,10.1016/s0040-4039(01)85756-7,1978-01-01,0.7240642786185283
Tetrahedron,Synthesis of [4.2]cyclophanes,,10.1016/s0040-4039(01)91442-x,1978-01-01,0.7240642786185283
Tetrahedron,Modern synthesis of carbamoyl fluorides,,10.1016/j.tetlet.2020.152539,2020-10-08,0.7240642786185283
Synthesis,Organometallics in Synthesis,,10.1055/s-1995-3962,1995-06-01,0.7240642786185283
Tetrahedron,Synthesis of Elasnin,,10.1016/s0040-4039(00)74555-2,1980-01-01,0.7240642786185283
Tetrahedron,"Synthesis of heterocycles : Synthesis of 4H-1,4-benzothiazines",,10.1016/0040-4039(80)80180-8,1980-01-01,0.7240642786185283
Tetrahedron,"Cationic cyclopentannelation. Synthesis of (d,1)-xanthocidin",,10.1016/s0040-4039(01)80391-9,1989-01-01,0.7240642786185283
Tetrahedron,Synthesis of cytidine diphosphate-d-quinovose,,10.1016/s0040-4039(01)80315-4,1989-01-01,0.7240642786185283
Tetrahedron,The synthesis of (±)-inositol-1-phosphonate,,10.1016/s0040-4039(01)80680-8,1989-01-01,0.7240642786185283
Tetrahedron,"Synthesis of diaza [7,7] paracyclophanetetraene and diaza [7,2,7,2] paracyclophanehexaene",,10.1016/s0040-4039(01)93887-0,1989-01-01,0.7240642786185283
Tetrahedron,"Stereodivergent synthesis of 1,3-polyols",,10.1016/s0040-4039(00)99367-5,1989-01-01,0.7240642786185283
Tetrahedron,"Enantiospecific synthesis of 5-phenylpyrrolo[2,1-c][1,4]benzodiazepines",,10.1016/j.tetlet.2008.09.168,2008-10-03,0.7240642786185283
Tetrahedron,Synthesis of 1-alkynylbicyclo[1.1.1]pentanes,,10.1016/s0040-4039(01)93718-9,1989-01-01,0.7240642786185283
Tetrahedron,Synthesis of l -2-spirocyclopropyl-2-deoxyarabinose,,10.1016/s0040-4039(01)80275-6,1989-01-01,0.7240642786185283
Tetrahedron,"Synthesis of l,l-isodityrosine",,10.1016/s0040-4039(01)93709-8,1989-01-01,0.7240642786185283
Tetrahedron,"Synthesis of furo[3,4-c]cephams",,10.1016/s0040-4039(00)93896-6,1976-09-01,0.7240642786185283
Tetrahedron,Allene synthesis from 2-alkyn-1-ols,,10.1016/s0040-4039(00)76187-9,1989-01-01,0.7240642786185283
Tetrahedron,A biogenetically modeled synthesis of eleutherin,,10.1016/s0040-4039(01)83682-0,1977-01-01,0.7240642786185283
Tetrahedron,The synthesis of (±)-Laurencin,,10.1016/s0040-4039(01)83805-3,1977-01-01,0.7240642786185283
Tetrahedron,Synthesis of γ-methylene butyrolactones (4-penten-4-olides),,10.1016/s0040-4039(01)83815-6,1977-01-01,0.7240642786185283
Tetrahedron,Biomimetic synthesis of alstonerine,,10.1016/s0040-4039(00)93893-0,1976-09-01,0.7240642786185283
Tetrahedron,Synthesis of Spatheliabischromene,,10.1016/s0040-4039(00)71327-x,1976-01-01,0.7240642786185283
Tetrahedron,Synthesis of bassianolide,,10.1016/s0040-4039(01)83423-7,1977-01-01,0.7240642786185283
Tetrahedron,Rearrangements in the pictet-gams isoquinoline synthesis,,10.1016/s0040-4039(01)83439-0,1977-01-01,0.7240642786185283
Tetrahedron,"Aminoglycoside antibiotics: synthesis of nebramine, tobramycin and 4″-epi-tobramycin",,10.1016/s0040-4039(01)83305-0,1977-01-01,0.7240642786185283
Tetrahedron,"Synthesis of 6β,7β-nitromethylene steroids",,10.1016/s0040-4039(01)83290-1,1977-01-01,0.7240642786185283
Tetrahedron,The synthesis of nitrocyclopropanes from nitrodiazomethanes,,10.1016/s0040-4039(01)80688-2,1989-01-01,0.7240642786185283
Tetrahedron,The synthesis of two 2′-deoxy carbocyclic purine nucleosides lacking the 5′-methylene,,10.1016/s0040-4039(00)97979-6,1990-01-01,0.7240642786185283
Tetrahedron,Synthesis of (+)-β-eudesmol,,10.1016/s0040-4039(01)99659-5,1966-01-01,0.7240642786185283
Tetrahedron,"The synthesis and valence isomerization of 1,2-diphenylcyclobutene",,10.1016/s0040-4039(00)72915-7,1966-01-01,0.7240642786185283
Tetrahedron,"Synthesis of 2,6-naphthyridine",,10.1016/s0040-4039(00)90042-x,1965-01-01,0.7240642786185283
Tetrahedron,The synthesis of primocarcin,,10.1016/s0040-4039(00)75125-2,1964-01-01,0.7240642786185283
Tetrahedron,Synthesis of pantherine (agarin),,10.1016/s0040-4039(00)90157-6,1965-01-01,0.7240642786185283
Tetrahedron,Synthesis of the C10-C34 segment of the immunosuppressant FK506,,10.1016/s0040-4039(00)89045-0,1990-01-01,0.7240642786185283
Tetrahedron,Synthesis of zephycandidine A from haemanthamine,,10.1016/j.tetlet.2020.151785,2020-02-26,0.7240642786185283
Tetrahedron,Synthesis of oxetanocin,,10.1016/s0040-4039(00)97210-1,1990-01-01,0.7240642786185283
Tetrahedron,A synthesis of the C16-C23 segment of FK-506,,10.1016/0040-4039(90)80037-m,1990-01-01,0.7240642786185283
Tetrahedron,A synthesis of dihydroanhydro--trimethylbrazilin and synthesis of --tetramethylbrazilin,,10.1016/s0040-4039(01)90939-6,1963-01-01,0.7240642786185283
Tetrahedron,Synthesis of a demethyltetracycline analog,,10.1016/s0040-4039(01)90883-4,1963-01-01,0.7240642786185283
Tetrahedron,Synthesis of chloroxanthin,,10.1016/s0040-4039(00)70394-7,1964-01-01,0.7240642786185283
Tetrahedron,Synthesis of psicofuranine,,10.1016/s0040-4039(00)70525-9,1962-01-01,0.7240642786185283
Tetrahedron,A synthesis of 3-isothiazolones,,10.1016/s0040-4039(01)89515-0,1964-01-01,0.7240642786185283
Tetrahedron,THE SYNTHESIS OF OROTIDINE,,10.1016/b978-1-4831-9886-6.50107-8,1963-01-01,0.7240642786185283
Tetrahedron,The synthesis of d1-n-methyldihydromenisarine,,10.1016/s0040-4039(00)70922-1,1962-06-01,0.7240642786185283
Tetrahedron,The synthesis of 3-azabicyclo[4.3.0]nonane scaffolds from brefeldin A,,10.1016/j.tetlet.2020.152006,2020-05-04,0.7240642786185283
Tetrahedron,THE SYNTHESIS OF D-CHALCOSE,,10.1016/b978-1-4831-9886-6.50103-0,1963-01-01,0.7240642786185283
Tetrahedron,THE SYNTHESIS OF EUPARIN AND DEHYDROTREMETONE,,10.1016/b978-1-4831-9886-6.50182-0,1963-01-01,0.7240642786185283
Tetrahedron,Regio- and stereocontrolled synthesis of hydroxycyclohexenyl sulfones from oxanorbornenes,,10.1016/s0040-4039(00)88836-x,1990-01-01,0.7240642786185283
Tetrahedron,An enantiospecific synthesis of (+)-isoparvifolinone and (−)-parvifoline,,10.1016/j.tetlet.2006.11.135,2006-12-14,0.7240642786185283
Tetrahedron,Synthesis of ginkgetin,,10.1016/s0040-4039(00)70874-4,1962-01-01,0.7240642786185283
Tetrahedron,Synthesis of 1-methylenepyrrolizidine,,10.1016/s0040-4039(01)99215-9,1961-01-01,0.7240642786185283
Tetrahedron,Synthesis of erythrocentaurin semicarbazone,,10.1016/s0040-4039(01)99235-4,1961-01-01,0.7240642786185283
Tetrahedron,Synthesis of atranorin,,10.1016/s0040-4039(00)70868-9,1962-01-01,0.7240642786185283
Tetrahedron,Constitution and synthesis of endocrocin,,10.1016/s0040-4039(00)70572-7,1962-01-01,0.7240642786185283
Tetrahedron,"Synthesis of 2,8-didehydro-9-noradamantanone",,10.1016/s0040-4039(00)99445-0,1989-01-01,0.7240642786185283
Tetrahedron,"An expeditious synthesis of (3S,4S)-statine and (3S,4S)cyclohexylstatine",,10.1016/s0040-4039(00)94374-0,1990-01-01,0.7240642786185283
Tetrahedron,Synthesis of salicylate dendritic prodrugs,,10.1016/j.tetlet.2006.08.110,2006-09-21,0.7240642786185283
Tetrahedron,Interfacial synthesis of bisphenol A tetrachlorocyclotriphosphazene from bisphenol A and hexachlorocyclotriphosphazene,,10.1016/j.tetlet.2013.07.098,2013-07-26,0.7240642786185283
Tetrahedron,Synthesis of 2-pentafluorosulfanylnaphthalene,,10.1016/j.tetlet.2006.12.123,2006-12-26,0.7240642786185283
Tetrahedron,First synthesis of 3-S-glutathionylhexanal-d and its bisulfite adduct,,10.1016/j.tetlet.2020.152100,2020-06-02,0.7240642786185283
Tetrahedron,Synthesis of the bottom half of chlorothricolide,,10.1016/s0040-4039(00)97640-8,1990-01-01,0.7240642786185283
Tetrahedron,Synthesis of a conformationally restricted polyoxygenated crownophane,,10.1016/j.tetlet.2005.08.036,2005-08-27,0.7240642786185283
Tetrahedron,A synthesis of lacrimin a,,10.1016/s0040-4039(00)99551-0,1989-01-01,0.7240642786185283
Tetrahedron,Synthesis of neurotoxic nephila spider venoms: NSTX-3 and JSTX-3,,10.1016/s0040-4039(01)80392-0,1989-01-01,0.7240642786185283
Tetrahedron,First synthesis of alpha glucosinolates,,10.1016/s0040-4039(00)97490-2,1990-01-01,0.7240642786185283
Tetrahedron,"Synthesis of 3′-deoxy-3′-(2-propynyl)thymidine and 3′-cyanomethyl-3′-deoxythymidine, analogs of AZT",,10.1016/s0040-4039(00)94577-5,1990-01-01,0.7240642786185283
Tetrahedron,The synthesis of (3R)-nerolidol,,10.1016/s0040-4039(00)97296-4,1990-01-01,0.7240642786185283
Tetrahedron,Phosphonium ylides in the multicomponent synthesis of pyrrolidines,,10.1016/j.tetlet.2022.154205,2022-10-19,0.7240642786185283
Tetrahedron,Synthesis of α-Trimethylsilylallenones,,10.1016/0040-4039(94)85201-4,1994-04-01,0.7240642786185283
Tetrahedron,"Synthesis of [3-13C]-2,3-dihydroxy-4-methoxybenzaldehyde",,10.1016/j.tetlet.2015.12.088,2015-12-23,0.7240642786185283
Tetrahedron,Synthesis of allyl sulfoxides from allylsilanes via silyl sulfinates,,10.1016/j.tetlet.2015.06.018,2015-06-14,0.7240642786185283
Tetrahedron,"Synthesis, mesomorphism and fluorescence of triphenylene-Bodipy dyads",,10.1016/j.tetlet.2016.09.082,2016-09-30,0.7240642786185283
Angewandte Chemie International Edition,Editorial Note: Diamond Synthesis in Doubt,,10.1002/anie.200461798,2004-09-07,0.7240642786185283
Tetrahedron,"Synthesis of penaresidin a, an azetidine alkaloid with actomyosin ATPase-activating property",,10.1016/0040-4039(95)01613-m,1995-10-01,0.7240642786185283
Tetrahedron,Kemp’s triacid scaffolding for synthesis of combinatorial nonpeptide uncoded libraries,,10.1016/00404-0399(50)1370-w,1995-09-01,0.7240642786185283
Tetrahedron,Synthesis of Antitumor Marine Steroid Aragusterols,,10.1016/00404-0399(50)1772a-,1995-11-06,0.7240642786185283
Tetrahedron,An enantiocontrolled synthesis of (−)-swainsonine,,10.1016/0040-4039(95)00920-8,1995-07-01,0.7240642786185283
Tetrahedron,Synthesis of a tetracyclic substructure of manzamine A,,10.1016/s0040-4039(00)60944-9,1992-10-01,0.7240642786185283
Tetrahedron,"Synthesis of benzo-fused, 7,5- and 7,6-fused azepinones as conformationally restricted dipeptide mimetics",,10.1016/0040-4039(95)00096-u,1995-03-01,0.7240642786185283
Tetrahedron,Synthesis of tetrasubstituted vicinal difluoroolefines,,10.1016/0040-4039(95)00934-5,1995-07-01,0.7240642786185283
Tetrahedron,Synthesis of neodysiherbaine,,10.1016/j.tetlet.2005.07.159,2005-08-16,0.7240642786185283
Tetrahedron,Synthesis of an actinorhodin monomer,,10.1016/0040-4039(95)01942-b,1995-12-01,0.7240642786185283
Tetrahedron,"Synthesis of 1,6-diaminodiamantane",,10.1016/0040-4039(95)01133-3,1995-08-01,0.7240642786185283
Tetrahedron,Synthesis of hyper-branched dendritic lactosides,,10.1016/0040-4039(95)00817-v,1995-06-01,0.7240642786185283
Tetrahedron,Synthesis of pentacoordinated tetraalkylammonium and tetraalkylphosphonium difluorosilicates,,10.1016/0040-4039(95)01841-5,1995-11-01,0.7240642786185283
Tetrahedron,Synthesis of (−)-neplanocin Avia C-H insertion of alkylidenecarbene,,10.1016/0040-4039(95)00081-m,1995-02-01,0.7240642786185283
Tetrahedron,Synthesis of pseudosugars from microbial metabolites,,10.1016/0040-4039(95)00347-f,1995-04-01,0.7240642786185283
Tetrahedron,Synthesis of stentorin,,10.1016/0040-4039(95)00248-b,1995-03-01,0.7240642786185283
Tetrahedron,Fluorous thiols in oligosaccharide synthesis,,10.1016/s0040-4039(04)00920-7,2004-05-26,0.7240642786185283
Tetrahedron,The synthesis of clavatadine C,,10.1016/j.tetlet.2016.10.019,2016-10-12,0.7240642786185283
European Journal of Organic Chemistry,Synthesis of reductones.,,,1940-01-01,0.7240642786185283
Tetrahedron,"Synthesis of dinaphthoporphyrins from dihydronaphtho[1,2-c]pyrroles",,10.1016/s0040-4039(00)77354-0,1994-10-10,0.7240642786185283
Tetrahedron,Photosensitized synthesis of phenanthrene heterocycles from 1- and 9-(aminoalkyl)phenanthrenes,,10.1016/s0040-4039(00)75831-x,1994-01-01,0.7240642786185283
Tetrahedron,Synthesis of interlocked basket handle porphyrins,,10.1016/s0040-4039(00)76887-0,1994-05-01,0.7240642786185283
Tetrahedron,"Synthesis of a Phosphatidylinositol 3,4,5-Trisphosphate",,10.1016/0040-4039(94)88179-0,1994-01-01,0.7240642786185283
Tetrahedron,Synthesis of (+)- and ($minus;)-isocarvone,,10.1016/s0040-4039(04)01017-2,2004-05-01,0.7240642786185283
Tetrahedron,Synthesis of the calophyllum coumarins,,10.1016/s0040-4039(00)73500-3,1994-07-01,0.7240642786185283
Tetrahedron,Synthesis of antifungal alatanone and trineurone polyketides,,10.1016/j.tetlet.2016.01.090,2016-01-27,0.7240642786185283
Tetrahedron,Regio- and stereocontrolled synthesis of d-erythro-sphingosine and phytosphingosine from d-glucosamine,,10.1016/s0040-4039(00)75806-0,1994-01-01,0.7240642786185283
Tetrahedron,"Synthesis of (2S,4S)-5-Fluoroleucine",,10.1016/s0040-4039(00)73531-3,1994-07-01,0.7240642786185283
Tetrahedron,The synthesis of conformationally/rotationally restricted analogs of the neurotransmitter serotonin,,10.1016/0040-4039(94)88158-8,1994-01-01,0.7240642786185283
Tetrahedron,Synthesis of epibatidine,,10.1016/s0040-4039(00)73514-3,1994-07-01,0.7240642786185283
Tetrahedron,Synthesis and stereochemical assignments for goniobutenolides A and B,,10.1016/s0040-4039(00)76941-3,1994-07-01,0.7240642786185283
Tetrahedron,"A steroidal cyclopeptide, synthesis and shape of the cavity",,10.1016/s0040-4039(00)75839-4,1994-01-01,0.7240642786185283
Tetrahedron,Synthesis of bromoxone,,10.1016/s0040-4039(00)78490-5,1994-11-01,0.7240642786185283
Tetrahedron,Synthesis of aziridines and azetidines from N-(ω-haloalkyl) imines,,10.1016/0040-4039(94)80039-1,1994-10-01,0.7240642786185283
Tetrahedron,Synthesis of carbazole analogs via Grob fragmentation of norbornyl α-diketones,,10.1016/j.tetlet.2016.06.080,2016-06-24,0.7240642786185283
Tetrahedron,Synthesis of ganglioside M5 from sea urchin egg,,10.1016/s0040-4039(00)77010-9,1994-04-01,0.7240642786185283
Tetrahedron,"Synthesis of 3′-deoxyadenosine-3′-spirocyclopropane, 3′-deoxy-uridine-3′-spirocyclopropane, and 5′-deoxy-4′,5′-methanoadenosine",,10.1016/s0040-4039(00)73206-0,1994-05-01,0.7240642786185283
Tetrahedron,"Synthesis and acidity of conformationally constrained 1,3-oxathiane S-oxides",,10.1016/j.tetlet.2016.10.114,2016-11-02,0.7240642786185283
Chemical Science,Tailor-made synthesis of multilayered trimetallocyclophanes via transannula Interactions,,,2016-06-28,0.7240642786185283
Tetrahedron,A synthesis of morphine-6-glucuronide,,10.1016/00404-0399(59)4398c-,1995-08-07,0.7240642786185283
Tetrahedron,Towards schizozygine: synthesis of 15α-hydroxystrempeliopine,,10.1016/j.tetlet.2005.09.098,2005-10-04,0.7240642786185283
Tetrahedron,Synthesis of alkenyl- and alkynylcyclopropenes,,10.1016/0040-4039(95)00634-o,1995-05-01,0.7240642786185283
Tetrahedron,Synthesis of Tetrasubstituted Vicinal Difluoroolefines,,10.1016/00404-0399(50)09345-,1995-07-10,0.7240642786185283
Tetrahedron,"Synthesis of α or β-aminodienes via the carbopalladation of 1,2-propadiene",,10.1016/0040-4039(95)00936-7,1995-07-01,0.7240642786185283
Tetrahedron,"Synthesis of α or β-Aminodienes via the Carbopalladation of 1,2-Propadiene",,10.1016/00404-0399(50)09367-,1995-07-10,0.7240642786185283
Tetrahedron,Electroreductive synthesis of acylsilanes from acylimidazoles,,10.1016/0040-4039(95)01888-o,1995-11-01,0.7240642786185283
Tetrahedron,Enantiospecific synthesis of (+)-paeonilactone C and (+)-paeniflorigenone from R-(−)-carvone,,10.1016/s0040-4039(00)78405-x,1994-10-10,0.7240642786185283
Tetrahedron,Synthesis of vicinal cyclopropanes,,10.1016/0040-4039(94)02269-h,1995-01-01,0.7240642786185283
Tetrahedron,Preorganization of Calix[8]arenes. Synthesis of Basket-Shaped Doubly-Crowned Calix[8]arenes,,10.1016/00404-0399(50)0997q-,1995-07-24,0.7240642786185283
Tetrahedron,A formal synthesis of (+)-asteltoxin,,10.1016/0040-4039(95)00476-s,1995-05-01,0.7240642786185283
Tetrahedron,Synthesis of antitumor marine steroid aragusterols,,10.1016/0040-4039(95)01772-a,1995-11-01,0.7240642786185283
Tetrahedron,Preorganization of calix[8]arenes. Synthesis of basket-shaped doubly-crowned calix[8]arenes,,10.1016/0040-4039(95)00997-q,1995-07-01,0.7240642786185283
Tetrahedron,A synthesis of morphine-6-glucuronide,,10.1016/0040-4039(95)00649-w,1995-05-01,0.7240642786185283
Tetrahedron,"Synthesis of azamacrolides — (±)Epilachnadiene, (±)Norepilachnene and (±)Homoepilachnene",,10.1016/0040-4039(94)02197-j,1995-01-01,0.7240642786185283
Tetrahedron,"Synthesis of(2R, 3R)-epoxyneral, a sex pheromone of the acarid mite, Caloglyphus sp. (Astigmata: Acaridae)",,10.1016/0040-4039(95)00063-i,1995-02-01,0.7240642786185283
Tetrahedron,Synthesis of hapalosin and 8-deoxy-hapalosin,,10.1016/0040-4039(96)01415-3,1996-09-01,0.7240642786185283
Tetrahedron,Synthesis of a C1C14 subunit of the macrodiolide antibiotics pamamycin-607 and pamamycin-635B,,10.1016/0040-4039(95)00471-n,1995-05-01,0.7240642786185283
Tetrahedron,Arg-Gly thiomethylene dipeptide surrogates: Synthesis and incorporation into Arg-Gly-Asp pseudotripeptides,,10.1016/s0040-4039(00)76226-5,1994-02-01,0.7240642786185283
Tetrahedron,Synthesis of dinucleoside phosphoramidimidates,,10.1016/s0040-4039(00)76666-4,1994-05-01,0.7240642786185283
Tetrahedron,"Synthesis of 2(3H)-imidazolethiones and 2(3H)-imidazolones from β,γ-alkynyl carbanilides",,10.1016/s0040-4039(00)76764-5,1994-03-01,0.7240642786185283
Tetrahedron,Synthesis of benzopurpurins isobacteriobenzopurpurins and bacteriobenzopurpurins,,10.1016/s0040-4039(00)73336-3,1994-06-01,0.7240642786185283
Tetrahedron,First enantiospecific synthesis of marine nor-sesquiterpene (+)-austrodoral from (−)-sclareol,,10.1016/j.tetlet.2005.06.010,2005-06-22,0.7240642786185283
Tetrahedron,Synthesis of trication stabilized by azulene rings,,10.1016/s0040-4039(00)75809-6,1994-01-01,0.7240642786185283
Tetrahedron,"Synthesis of 2,2-dichloroindane-1,3-diones from 1,4-naphthoquinones",,10.1016/s0040-4039(00)73090-5,1994-05-01,0.7240642786185283
Tetrahedron,Enantiospecific synthesis of (+)-paeonilactone C and (+)-paeoniflorigenone from R-(−)-carvone,,10.1016/0040-4039(94)80031-6,1994-10-01,0.7240642786185283
Tetrahedron,Hepoxilins B3: Synthesis of all four stereoisomers and a glutathione adduct,,10.1016/s0040-4039(00)73491-5,1994-07-01,0.7240642786185283
Tetrahedron,"Synthesis of β configured 2′,3′-unsaturated pentopyranosyl nucleosides",,10.1016/0040-4039(94)02466-o,1995-02-01,0.7240642786185283
Tetrahedron,Synthesis of aziridines and azetidines from N-(ω)-haloalkyl) imines,,10.1016/s0040-4039(00)78413-9,1994-10-10,0.7240642786185283
Tetrahedron,An enantiocontrolled synthesis of (−)-Swainsonine,,10.1016/00404-0399(50)09208-,1995-07-10,0.7240642786185283
Tetrahedron,Synthesis of a Dinucleotide Phosphoramidimidate,,10.1016/00404-0399(50)1384t-,1995-09-18,0.7240642786185283
Tetrahedron,Synthesis of a dinucleotide phosphoramidimidate,,10.1016/0040-4039(95)01384-t,1995-09-01,0.7240642786185283
Tetrahedron,Synthesis of (1-13C)-1-Deoxynojirimycin,,10.1016/00404-0399(50)0959g-,1995-07-10,0.7240642786185283
Tetrahedron,Synthesis of polyammonium macrocycles with pendant chains,,10.1016/0040-4039(95)00206-r,1995-03-01,0.7240642786185283
Tetrahedron,Synthesis of (1-13C)-1-deoxynojirimycin,,10.1016/0040-4039(95)00959-g,1995-07-01,0.7240642786185283
Tetrahedron,Synthesis of conformationally locked analogs of quinolin-6-yloxyacetamide fungicides,,10.1016/j.tetlet.2016.10.104,2016-10-29,0.7240642786185283
Tetrahedron,An expeditious synthesis of 6-aminophenanthridines,,10.1016/j.tetlet.2005.03.135,2005-04-09,0.7240642786185283
Tetrahedron,"Synthesis of 1,6-Diaminodiamantane",,10.1016/00404-0399(50)11333-,1995-08-07,0.7240642786185283
Tetrahedron,"Spiroketal equilibration: Interconversion of 1,6-dioxaspiro[4.4]nonanes and 1,6-dioxaspiro[4.5]decanes. Implications for the synthesis of cephalostatin 7",,10.1016/s0040-4039(00)73506-4,1994-07-01,0.7240642786185283
Tetrahedron,Stereochemical outcome of benzyllithiums synthesis from selenides,,10.1016/s0040-4039(00)92094-x,1992-06-01,0.7240642786185283
Tetrahedron,A synthesis of (−)-indolactam V,,10.1016/s0040-4039(00)60300-3,1993-02-01,0.7240642786185283
Tetrahedron,Synthesis of L-ornithines stereospecifically deuterated at C-3,,10.1016/s0040-4039(00)79263-x,1993-06-01,0.7240642786185283
Tetrahedron,Synthesis of C-2 methylene glycosides from C-2 propargyloxymethyl glycals exploiting the alkynophilicity of AuCl3,,10.1016/j.tetlet.2007.10.144,2007-11-20,0.7240642786185283
Tetrahedron,Synthesis of 1-epihydantocidin from d-ribose,,10.1016/s0040-4039(00)73695-1,1993-05-01,0.7240642786185283
Tetrahedron,Synthesis of (+)-8-deoxyvernolepin,,10.1016/s0040-4039(00)60627-5,1993-06-01,0.7240642786185283
Tetrahedron,"Synthesis of dithieno[3,2-b:2′,3′-e]pyridines and 4,8-dihydrodithieno[3,2-b:2′,3′-e]pyridines",,10.1016/s0040-4039(00)73842-1,1993-09-01,0.7240642786185283
Tetrahedron,"Synthesis of 1,4-(1,1′-ferrocenediyl)-1,3-butadiene: A dieno-ferrocenophane.",,10.1016/s0040-4039(00)60545-2,1993-01-01,0.7240642786185283
Tetrahedron,Synthesis of o-dimethylene isoxazole via isoxazole-fused 3-sulfolene,,10.1016/s0040-4039(00)74736-8,1992-12-01,0.7240642786185283
Tetrahedron,A biomimetic synthesis of homofascaplysin C from ditryptophans,,10.1016/j.tetlet.2016.02.014,2016-02-04,0.7240642786185283
Tetrahedron,Regiocontrol in the synthesis of naphthoquinones. Regiospecific synthesis of lomandrone and aristolindiquinone,,10.1016/s0040-4039(00)60555-5,1993-01-01,0.7240642786185283
Tetrahedron,Synthesis of tetranor-PGE1: A urinary metabolite of prostaglandins E1 and E2,,10.1016/j.tetlet.2020.151922,2020-04-10,0.7240642786185283
Tetrahedron,Synthesis of bacilosarcins B and C,,10.1016/j.tetlet.2016.09.090,2016-09-30,0.7240642786185283
Tetrahedron,Synthesis of tetrahydropyranyl diarylheptanoids from Dioscorea villosa,,10.1016/j.tetlet.2016.06.102,2016-06-23,0.7240642786185283
Tetrahedron,"Synthesis of 1,5-dideoxy-1,5-imino-d-galactitol from l-sorbose",,10.1016/s0040-4039(00)73649-5,1993-05-01,0.7240642786185283
Tetrahedron,First synthesis of oxa-analogous isoindigo-N-glycosides,,10.1016/j.tetlet.2007.11.057,2007-11-26,0.7240642786185283
Tetrahedron,Synthesis of 1-allyloxy-1-siloxycyclopropanes and 1-propargyloxy-1-siloxycyclopropanes,,10.1016/s0040-4039(00)77715-x,1992-02-01,0.7240642786185283
Tetrahedron,The synthesis of 7α-amidocarbacephems,,10.1016/s0040-4039(00)74239-0,1992-07-01,0.7240642786185283
Tetrahedron,An enantiospecific synthesis of solenopsin A,,10.1016/s0040-4039(00)60479-3,1993-04-01,0.7240642786185283
Tetrahedron,"Serendipitous synthesis of diaxial 2,4-diphenyl-3,7-dioxabicyclo[3.3.0]octane",,10.1016/s0040-4039(00)74260-2,1992-07-01,0.7240642786185283
Tetrahedron,Synthesis of tetracenomycins,,10.1016/s0040-4039(00)61155-3,1992-09-01,0.7240642786185283
Tetrahedron,The synthesis of ceramide phosphoinositol,,10.1016/s0040-4039(00)92684-4,1992-06-01,0.7240642786185283
Tetrahedron,"A stereocontrolled synthesis of a C19-C32 / C17-C30 Segment for swinholide A and misakinolide A, Cytotoxic dimeric macrolides from theonella swinhoei.",,10.1016/s0040-4039(00)78876-9,1992-05-01,0.7240642786185283
Tetrahedron,Synthesis of (pyridinio-phenoxide) zwitterions,,10.1016/0040-4039(92)89020-d,1992-09-01,0.7240642786185283
Tetrahedron,Synthesis of upper rim calix[4]arene carcerands,,10.1016/j.tetlet.2007.11.115,2007-11-26,0.7240642786185283
Tetrahedron,The synthesis of 2-azido C-glycosyl sugars,,10.1016/s0040-4039(00)79826-1,1992-05-01,0.7240642786185283
Tetrahedron,On the synthesis of isoannulated pyrroles and δ-pyridones,,10.1016/s0040-4039(00)77673-8,1992-01-01,0.7240642786185283
Tetrahedron,"Synthesis of indolizine-5,8-diones and [3.2.2]cyclazines",,10.1016/s0040-4039(00)74750-2,1992-12-01,0.7240642786185283
Tetrahedron,Synthesis of the liposidomycin diazepanone,,10.1016/s0040-4039(00)61123-1,1992-09-01,0.7240642786185283
Tetrahedron,"Enantiospecific synthesis of functionalised indolizidines. Synthesis of (8S, 8aR)-6,7-dehydro-8-hydroxyindolizidine.",,10.1016/s0040-4039(00)61793-8,1992-11-01,0.7240642786185283
Tetrahedron,Synthesis of combretastatin D-2+,,10.1016/s0040-4039(00)74692-2,1992-07-01,0.7240642786185283
Tetrahedron,Diversity oriented synthesis of benzoxazoles and benzothiazoles,,10.1016/j.tetlet.2007.10.067,2007-11-20,0.7240642786185283
Tetrahedron,Synthesis and cycloreversion of benzocyclobutene- and benzocyclobutadiene-anthracene adducts,,10.1016/0040-4039(92)88065-d,1992-01-01,0.7240642786185283
Tetrahedron,A stereodivergent chirospecific synthesis of (3R) and (3S) 3-hydroxyaspartates by hydroxylation of aspartate diester enolates,,10.1016/s0040-4039(00)61333-3,1992-08-01,0.7240642786185283
Tetrahedron,"Stereocontrolled synthesis of 1,7a-diepialexine",,10.1016/s0040-4039(00)92240-8,1992-04-01,0.7240642786185283
Tetrahedron,"The synthesis of facial amphiphile 3α,7α-diaminocholestane",,10.1016/j.tetlet.2007.05.157,2007-06-04,0.7240642786185283
Tetrahedron,Synthesis of cyclometaphenylene under nanoconfinement and further derivatization,,10.1016/j.tetlet.2023.154679,2023-08-02,0.7240642786185283
Tetrahedron,An exceptionally brief synthesis of eupolauramine,,10.1016/s0040-4039(00)60002-3,1992-10-01,0.7240642786185283
Tetrahedron,A formal synthesis of (+)-juvabione,,10.1016/s0040-4039(00)92317-7,1992-01-01,0.7240642786185283
Angewandte Chemie International Edition,Synthesis of Acylpolyamines: Acetylspermidines and C12:0 Acarnidine,,10.1002/anie.198308600,1983-08-01,0.7240642786185283
Tetrahedron,Stereocontrolled synthesis of hyaluronan tetrasaccharide,,10.1016/s0040-4039(00)61248-0,1992-08-01,0.7240642786185283
Tetrahedron,Fluorodehydroxylation of anthracyclinones with DAST synthesis of 8-(S)-fluorodaunorubicin,,10.1016/s0040-4039(00)60660-3,1993-09-01,0.7240642786185283
Tetrahedron,A stereocontrolled synthesis of the left hand (C1–C12) segment of eurylene,,10.1016/s0040-4039(00)60792-x,1993-03-01,0.7240642786185283
Tetrahedron,Synthesis of phosphorylated tripeptides representing poisoned acetylcholinesterase,,10.1016/0040-4039(93)88096-2,1993-10-01,0.7240642786185283
Tetrahedron,Synthesis of selenolates from stannyl and silyl alkylselenides,,10.1016/s0040-4039(00)61374-6,1993-01-01,0.7240642786185283
Tetrahedron,Synthesis of hadinecine,,10.1016/s0040-4039(00)73623-9,1993-05-01,0.7240642786185283
Tetrahedron,Synthesis of the C1?C27 portion of the aplyronines,,10.1016/s0040-4039(04)00979-7,2004-05-01,0.7240642786185283
Tetrahedron,"Hauser annulation of furoindolones in the synthesis of carbazole-1,4-quinones and benzo[b]carbazoloquinones",,10.1016/j.tetlet.2015.09.081,2015-09-26,0.7240642786185283
Tetrahedron,"Synthesis of α- and/or γ-benzoyloxy-α,β-enones from α-halo-α,β-enones",,10.1016/j.tetlet.2004.11.119,2004-12-16,0.7240642786185283
Tetrahedron,Synthesis of 818-ethanoretinal and its interaction with apo-retinochrome,,10.1016/s0040-4039(00)77494-6,1993-02-01,0.7240642786185283
Tetrahedron,Hydroboration of enecarbamates and the synthesis of β-hydroxypiperidine alkaloids,,10.1016/s0040-4039(00)60402-1,1993-11-01,0.7240642786185283
Tetrahedron,Synthesis of a cradle cyclodextrin,,10.1016/s0040-4039(00)73628-8,1993-05-01,0.7240642786185283
Tetrahedron,Synthesis of the trioxadecalin-part of mycalamide B,,10.1016/s0040-4039(00)61506-x,1993-12-01,0.7240642786185283
Tetrahedron,Synthesis of α-oxazolinylalkanamides,,10.1016/j.tetlet.2004.09.006,2004-09-21,0.7240642786185283
Tetrahedron,Synthesis of D-erythro-sphingomyelin and of D-erythro-ceramide-1-phosphoinositol,,10.1016/s0040-4039(00)91820-3,1993-10-01,0.7240642786185283
Tetrahedron,"Synthesis of 2,5-dilithio-1-methylimidazole",,10.1016/s0040-4039(00)79166-0,1993-05-01,0.7240642786185283
Tetrahedron,"Synthesis of 6-oxa-1,5-pentamethylenetetrazoles (sugar tetrazoles)",,10.1016/s0040-4039(00)60686-x,1993-08-01,0.7240642786185283
Tetrahedron,Synthesis of a guanidino-sugar as a glycosyl cation mimic,,10.1016/s0040-4039(00)73215-1,1994-05-01,0.7240642786185283
Tetrahedron,"Synthesis of (±) 1,2-dideoxy-1,2-diamino-myo-inositol",,10.1016/0040-4039(94)85318-5,1994-10-01,0.7240642786185283
Tetrahedron,Synthesis of 9-deoxotaxane analogs,,10.1016/s0040-4039(00)76947-4,1994-07-01,0.7240642786185283
Tetrahedron,Synthesis of E- and Z-alkene dipeptide isosteres,,10.1016/s0040-4039(00)73956-6,1993-08-01,0.7240642786185283
Tetrahedron,Synthesis of (±) Fredericamycin A,,10.1016/s0040-4039(00)77651-9,1993-04-01,0.7240642786185283
Tetrahedron,"Biomimetic synthesis of pyrido [2,3,4-kl]acridines",,10.1016/s0040-4039(00)60789-x,1993-03-01,0.7240642786185283
Tetrahedron,"Synthesis of 1,3,3-trinitroazetidine",,10.1016/s0040-4039(00)61673-8,1993-10-01,0.7240642786185283
Tetrahedron,"The synthesis of isoxazoles from β,γ-acetylenic oximes",,10.1016/s0040-4039(00)60061-8,1993-01-01,0.7240642786185283
Tetrahedron,"Synthesis of 1,2-dioxanes from an endoperoxide",,10.1016/s0040-4039(00)60854-7,1992-11-01,0.7240642786185283
Tetrahedron,Synthesis of the C21–C28 segment of pectenotoxin-4,,10.1016/j.tetlet.2007.04.148,2007-05-06,0.7240642786185283
Tetrahedron,Synthesis of (±)-coerulescine and a formal synthesis of (±)-horsfiline,,10.1016/j.tetlet.2005.10.015,2005-10-27,0.7240642786185283
Tetrahedron,Synthesis of isotopically labelled ubiquinones,,10.1016/s0040-4039(00)61251-0,1992-08-01,0.7240642786185283
Tetrahedron,Synthesis of viologen-tagged oligodeoxynucleotides,,10.1016/s0040-4039(00)93980-7,1992-01-01,0.7240642786185283
Tetrahedron,Synthesis of phosphonate analogs of lipid X,,10.1016/s0040-4039(00)93372-0,1993-05-01,0.7240642786185283
Tetrahedron,Synthesis of neocarzilin A: An absolute streochemistry,,10.1016/s0040-4039(00)60821-3,1992-01-01,0.7240642786185283
Tetrahedron,β-Hydroxysilanes in the synthesis and labelling of unsaturated pheromones,,10.1016/0040-4039(93)85015-o,1993-03-01,0.7240642786185283
Tetrahedron,"Synthesis of (4S, 5S, 11R) and (4S, 5S, 11S)-iso-cladospolide B",,10.1016/j.tetlet.2013.04.124,2013-05-07,0.7240642786185283
Tetrahedron,Synthesis of 6-methylpretetramid,,10.1016/s0040-4039(00)60658-5,1993-09-01,0.7240642786185283
Tetrahedron,Synthesis of (+)-Gabosines C and E from D-ribose,,10.1016/s0040-4039(00)73150-9,1994-06-01,0.7240642786185283
Tetrahedron,"Synthesis and nonplanar macrocyclic characters of hexa-, octa-, and decaphenylporphyrins",,10.1016/s0040-4039(00)73239-4,1994-05-01,0.7240642786185283
Tetrahedron,"The synthesis of roeharmine and (−)-1,2,3,4-tetrahydroroeharmine",,10.1016/s0040-4039(00)73513-1,1994-07-01,0.7240642786185283
Tetrahedron,"Synthesis of dinaphthoporphyrins from dihydronaphtho[1,2-c]pyrroles",,10.1016/0040-4039(94)80100-2,1994-10-01,0.7240642786185283
Tetrahedron,"The synthesis of 4,4′(5′)-diformyltetrathiafulvalene",,10.1016/0040-4039(94)88478-1,1994-12-01,0.7240642786185283
Tetrahedron,A synthesis of the spiroketal subunit of (−)-calyculin A,,10.1016/s0040-4039(00)73111-x,1994-06-01,0.7240642786185283
Tetrahedron,Synthesis of aminomethylated calix[4]resorcinarenes,,10.1016/s0040-4039(00)60145-4,1993-11-01,0.7240642786185283
Organic Process Research & Development,Development of an Efficient and Scalable Process of a Respiratory Syncytial Virus Inhibitor,"An improved process has been developed for compound 1, a respiratory syncytial virus (RSV) inhibitor. This improved process is convergent, safe, efficient, and useful to prepare compound 1 in kilogram quantities.",10.1021/op049899l,2004-09-30,0.7240594202580195
Tetrahedron,"Synthesis of chiral zileuton, a potent and selective inhibitor of 5-lipoxygenase",,10.1016/s0040-4039(00)79043-5,1992-05-01,0.7238178613290589
Organic Process Research & Development,An Alternate and Efficient Synthetic Process for a Metabolic Dysfunction-Associated Steatohepatitis Drug: Resmetirom,"A novel, efficient, and streamlined process was developed for resmetirom, a first-in-class THR-β agonist for the treatment of MASH. The key innovation of this novel process was the ingenious utilization of a “one-pot” reaction, which simultaneously accomplished aromatic cyclization and the hydrolysis of 3-chloro-4-isopropylpyridazine. This breakthrough circumvented steps of amino protection and deprotection, effectively streamlining the synthetic route from eight linear steps to four steps while maintaining mild reaction conditions. Using commercially available raw materials, the optimized process provided a rapid pathway to synthesize multigram quantities of resmetirom with an assay purity of 98.8% and a corrected overall yield of 44.3%.",10.1021/acs.oprd.5c00149,2025-09-10,0.7237896981806955
Journal of Organic Chemistry,A Concise Route to (+)-Lactacystin,"A facile chromatography-free route to Kang's intermediate for the synthesis of (+)-lactacystin, a potent proteasome inhibitor, has been developed starting with Brown's asymmetric crotylation of tert-butyl 5-formyl-2,2-dimethyl-1,3-dioxan-5-ylcarbamate, easily available from 2-amino-2-(hydroxymethyl)propane-1,3-diol (Tris).",10.1021/jo048817o,2004-09-29,0.7236992874790295
Synthesis,Practical Synthesis of KRN7000 from Phytosphingosine,"The efficient and practical synthesis of the biologically important α-galactosylceramides, KRN7000, from phytosphingosine has been achieved in six steps in high overall yield.",10.1055/s-2004-822315,2004-01-01,0.7235946154681524
Angewandte Chemie International Edition,Scalable Enantioselective Total Synthesis of (−)‐Goniomitine,"A scalable enantioselective total synthesis of (-)-goniomitine has been developed by using an iridium-catalyzed asymmetric hydrogenation of an exocyclic enone ester to control the configuration of the molecule. The synthesis begins from commercially available starting materials, and proceeds through an integrated asymmetric ketone hydrogenation, Johnson-Claisen rearrangement, and one-pot oxidation/deprotection/cyclization process. With this highly efficient and scalable strategy, (-)-goniomitine was synthesized in eleven steps with 27 % overall yield, and formal enantioselective syntheses of (+)-1,2-dehydroaspidospermidine, (+)-aspidospermidine, and (+)-vincadifformine were also achieved.",10.1002/anie.201812822,2018-12-06,0.7235702793446467
Journal of Organic Chemistry,Synthesis of <i>N</i>-Methyl-<i>N</i>-{(1<i>S</i>)-1-[(3<i>R</i>)-pyrrolidin-3-yl]ethyl}amine,"N-Methyl-N-[(1S)-1-[(3R)-pyrrolidin-3-yl]ethyl]amine (1)(1) is a key intermediate in the preparation of premafloxacin (2), which was under development as an antibiotic for use against pathogens of veterinary importance. This paper describes the development of a practical, efficient, and stereoselective process for the preparation of 1 from isobutyl (3S)-3-[methyl[(1S)-1-phenylethyl]amino]butanoate (5c). The key steps in the synthetic sequence are an asymmetric Michael addition, which yields 5c, and a stereoselective alkylation, which yields (3S,4S)-3-allyl-1,4-dimethylazetidin-2-one (17).",10.1021/jo0349633,2003-11-19,0.7232959476685729
European Journal of Organic Chemistry,Improvements in the Total Synthesis of Morphine,"The chiral 1,2,3,4-tetrahydroisoquinoline intermediates in the Rice and Beyerman routes to morphine, (+)-(R)-1-(3-hydroxy-4-methoxybenzyl)-6-methoxy-1,2,3,4-tetrahydroisoquinoline (6) and (+)-(R)-1-(3,5-dibenzyloxy-4-methoxybenzyl)-6-methoxy-1,2,3,4-tetrahydroisoquinoline (5), were prepared in high ee by ruthenium-catalyzed asymmetric transfer hydrogenation of the corresponding imine precursors (Noyori method). The yield of the key raw material in the Beyerman route, 3,5-dibenzyloxy-4-methoxyphenylacetic acid (1), starting from gallic acid methyl ester (7) was improved by a factor of 5 over previously described syntheses. Key steps in the new procedure are the selective formation of methyl 3,5-dihydroxy-4-methoxybenzoate (9) via the 3,5-diacetate and an improved benzylation of the hydroxyl groups in 9.",10.1002/(sici)1099-0690(199909)1999:9<2315::aid-ejoc2315>3.0.co;2-v,1999-09-01,0.7230775377775358
Tetrahedron,Synthesis of aspergillide A from a synthetic intermediate of aspergillide B,,10.1016/j.tetlet.2009.12.032,2009-12-12,0.7229340595787299
Journal of Organic Chemistry,"Development of the Large-Scale Synthesis of Tetrahydropyran Glycine, a Precursor to the HCV NS5A Inhibitor <b>BMS-986097</b>","An efficient large-scale synthesis of acid 1, a penultimate precursor to the HCV NS5A inhibitor BMS-986097, along with the final API step are described. Three routes were devised for the synthesis of 1 at the various stages of the program. The third generation route, the one that proved scalable and is the main subject of this paper, features a one-step Michael addition of t-butyl 2-((diphenylmethylene)amino)acetate (24) to (E)-benzyl 4-(1-hydroxycyclopropyl)but-2-enoate (28) followed by cyclization and chiral separation to form 27c, the core skeleton of cap piece 1. The epimerization and chiral resolution of 27c followed by further synthetic manipulations involving the carbamate formation, lactone reduction and cyclization, afforded cyclopropyl pyran 1. A detailed study of diphenylmethane deprotection via acid hydrolysis as well as a key lactone to tetrahydropyran conversion, in order to avoid a side reaction that afforded an alternative cyclization product, are discussed. This synthesis was applied to the preparation of more than 100 g of the final API BMS-986097 for toxicology studies.",10.1021/acs.joc.7b01852,2017-09-07,0.7228365848811812
Journal of Organic Chemistry,A Scalable Synthesis of a Histamine H<sub>3</sub> Receptor Antagonist,"Starting from 1-methylimidazole, a concise, scalable, three-step synthesis of the title compound is described. The required 2-chloroimidazole was prepared in very good yield by halogen-metal exchange between the 2-lithio derivative and hexachloroethane.",10.1021/jo040225i,2004-10-19,0.7228343899704769
Organic Letters,Total Synthesis of (−)-Chamobtusin A,"The first asymmetric total synthesis of a structurally unique alkaloid, chamobtusin A (1), is described. The route features a novel aziridine formation from the 1,2-oxazine derivative and a palladium-mediated annulation of the vinylaziridine intermediate.",10.1021/ol302880x,2012-11-30,0.7228182656461076
Organic Process Research & Development,A Concise Synthesis of a Novel Insulin-Like Growth Factor I Receptor (IGF-IR) Inhibitor,"An efficient synthesis of a potent insulin-like growth factor I receptor (IGF-IR) inhibitor AEW541 (1) is described. The key step in the synthesis is the cis -selective reductive amination of cyclobutanone, which sets up the desired 1,3-stereochemistry of the cyclobutane ring. The amino group thus generated is used as a handle to build the pyrrolopyrimidine ring. The final step resulting in 1 is accomplished by alkylation of in situ generated mesylate with azetidine.",10.1021/op700052u,2007-08-14,0.722806292379222
Organic Letters,Stereocontrolled and Efficient Total Synthesis of (−)-Stephanotic Acid Methyl Ester and (−)-Celogentin C,"A highly stereocontrolled and efficient total synthesis of (-)-stephanotic acid methyl ester and (-)-celogentin C was accomplished in longest linear 14 steps (4.6% overall yield) and in 20 steps (1.6% overall yield) from l-tryptophan, respectively. Highlights of the synthesis include a tandem asymmetric Michael addition/bromination/azidation strategy for a ready access to the leucine-tryptophan moiety (Leu-Trp linkage) and an oxidative coupling reaction to form the indole-imidazole linkage.",10.1021/ol902944f,2010-01-28,0.722721779149329
Tetrahedron,An asymmetric synthesis of a key intermediate to 1β-methylcarbapenem antibiotics,,10.1016/00404-0399(50)1359-p,1995-09-01,0.7226835707185456
Tetrahedron,Asymmetric synthesis of a key camptothecin intermediate from 2-fluoropyridine,,10.1016/0040-4039(95)01665-5,1995-10-01,0.7226835707185456
Tetrahedron,An asymmetric synthesis of a key intermediate to 1β-methylcarbapenem antibiotics,,10.1016/00404-0399(50)1359p-,1995-09-11,0.7226835707185456
Tetrahedron,An asymmetric synthesis of a key intermediate to 1β-methylcarbapenem antibiotics,,10.1016/0040-4039(95)01359-p,1995-01-16,0.7226835707185456
Organic Process Research & Development,Efficient Synthesis of a 5-HT<sub>2C</sub> Receptor Agonist Precursor,"A short, scaleable, synthetic approach toward the tricyclic indole derivative 2, an intermediate in the synthesis of the 5-HT 2C agonist 1, is described. The synthesis started with Williamson etherification of inexpensive 4-nitro-3-methylphenol ( 11 ) followed by reduction to the corresponding aniline 13 and subsequent Boc protection. Acylation of the methyl group in 14 via lithiation furnished γ-chloroketone 16, which was subjected to acid promoted indole formation to afford 17 . In the final step, NaOH induced hydrolytic cleavage of the Boc protecting group followed by direct intramolecular nucleophilic substitution gave rise to target molecule 2 in an overall yield of 65% over six steps.",10.1021/op050065s,2005-06-28,0.7220652149513302
European Journal of Organic Chemistry,Second Generation Total Synthesis of (–)‐Preussochromone D,"An improved enantioselective synthesis of the natural product (–)‐preussochromone D ( 3 ) and first insights into a possible route to the trans ‐preussochromones E and F are described. Starting from commercially available 5‐hydroxy‐4 H ‐chromen‐4‐one, two stereocenters are established via auxiliary controlled Michael addition in excellent yield and stereoselectivity. Subsequent build‐up of the five‐membered ring gave access to (–)‐preussochromone D in an improved overall yield and less synthetic steps than previously reported. The total syntheses of preussochromones E and F on a related route were also investigated and first findings are reported herein.",10.1002/ejoc.202000465,2020-04-28,0.7220639635372365
Journal of Organic Chemistry,"Synthesis of Methyl <i>N</i>-Boc-(2<i>S</i>,4<i>R</i>)-4-methylpipecolate","An efficient stereoselective synthesis of fully protected (2S,4R)-4-methylpipecolic acid has been developed. The synthesis was achieved by initial asymmetric α-alkylation of glycine with a chiral iodide, affording the linear precursor as a single stereoisomer. Subsequent aldehyde formation using OsO(4)/NaIO(4) followed by immediate intramolecular cyclization afforded an enamine that was then subjected to hydrogenation to give the final compound in 23% yield over 10 steps.",10.1021/jo102038q,2010-11-23,0.7220178276138777
Synlett,An Expeditious Method for the First Asymmetric Synthesis of Dexoxadrol from the Chiral Pool,"A new, straightforward and high-yielding methodology for the asymmetric synthesis of 2-(1,3-dioxolan-4-yl)piperidines is described. This approach involves a highly stereoselective addition of vinylmagnesium bromide to N-(3-butenyl)imines derived from d-glyceraldehyde diphenyl ketal and a ring-closing metathesis reaction as key steps. This procedure was used for the first asymmetric synthesis of (S)-2-[(S)-2,2-diphenyl-1,3-dioxolan-4-yl]piperidine (dexoxadrol) starting from conveniently protected d-mannitol in six steps in 43% overall yield.",10.1055/s-0030-1258110,2010-06-30,0.7219903970037593
Journal of Organic Chemistry,Synthesis of (±)-Rosaprostol,"A total synthesis of racemic rosaprostol, an untiulcer drug, has been achieved in seven synthetic steps and in 42% overall yield starting from dimethyl methanephosphonate. The key steps include intramolecular carbenoid cyclization of dimethyl 1-diazo-2-oxoundecanephosphonate 4 leading to 2-dimethoxyphosphoryl-3-hexylcyclopentanone 5 and the Horner−Wittig reaction of the latter with methyl 5-formylpentanecarboxylate 6 employed for the introduction of the methoxycarbonylhexyl moiety at C(2) of the cyclopentanone ring.",10.1021/jo981120g,1998-10-30,0.7218053259714735
Organic Process Research & Development,"Development of a Manufacturing Process for a Key (<i>S</i>)-5-(2,2-Dimethyltetrahydro-2<i>H</i>-pyran-4-yl)-1<i>H</i>-indole Intermediate for Orforglipron. Part I. Selection of an Evans Auxiliary-Assisted Asymmetric 1,4-Addition Route","Two synthetic strategies for key ( S )-5-(2,2-dimethyltetrahydro-2 H -pyran-4-yl)-1 H -indole intermediate 1 for orforglipron were demonstrated. The Negishi cross-coupling route was initially scaled up to deliver a total of 36.6 kg of compound 1 to support the production of orforglipron to fund early clinical trials. However, this route was nonenantioselective and required laborious chiral SFC purification to obtain an optically pure intermediate. An enantioselective route featuring Evans auxiliary-assisted asymmetric 1,4-addition successfully produced the desired product without necessitating nonscalable chromatographic purification throughout the synthesis, which was selected for further development into a robust process for large-scale production.",10.1021/acs.oprd.5c00183,2025-08-05,0.7217428220904958
Organic Letters,"Total Synthesis of 7′,8′-Dihydroaigialospirol","A highly convergent total synthesis of 7',8'-dihydroaigialospirol is described. Key steps of the synthesis include a Nozaki-Hiyama-Kishi (NHK) coupling of an iodoalkyne with an advanced phthalide-aldehyde and a remarkable one-pot acid-mediated global deprotection/spiroacetalization.",10.1021/ol302498v,2012-09-27,0.7217377853067104
Organic Process Research & Development,Process Development of a Large-Scale Synthesis of TKA731:  A Tachykinin Receptor Antagonist,"An efficient and chromatography-free large-scale synthesis of a tachykinin receptor antagonist TKA731 ( 1 ), utilizing the coupling of dipeptide 7 and 2-chloro-4( 3H )-quinazolinone ( 13 ) as the key step, is described. The overall yield of 1 from BOC- l -3-(2-naphthyl)alanine ( 2 ) in six linear steps (total of eight steps) is 63%. This new convergent approach avoided the use of methyl iodide and the formation of methanethiol byproduct in the last step involving the construction of the quinazolinone ring in the original discovery synthesis. Four chromatographies were also eliminated. The main cause of the side reaction, leading to the urethane byproduct ( I ) formation and starting amino acid ( 2 ) liberation during the coupling of 2 with N -benzylmethylamine using well-known isobutyl chloroformate mediated mixed carboxylic-carbonic anhydride method, was found to be the symmetrical anhydride ( III ) formation from 2 as determined by the CO 2 offgas formation. A new procedure for the coupling of 2 with N -benzylmethylamine involving a reverse addition of 2 and the base to the coupling agent isobutyl chloroformate, followed by the addition of the amine, was developed that minimized the symmetrical anhydride formation. A novel, water-assisted N -methylation of 5 with dimethyl sulfate in the presence of sodium hydride in THF was also developed that eliminated the use of methyl iodide, silver oxide, and KCN. Deprotection of the BOC group in 6 with sulfuric acid circumvented the formation of diketopiperazine and tetrapeptide observed with HCl and trifluoroacetic acid, respectively.",10.1021/op0341824,2004-03-17,0.7216440774825216
Organic Process Research & Development,"Development of a Practical and Efficient Synthesis of SIPI-4884, a HMG CoA Reductase Inhibitor for the Treatment of Hypercholesterolemia","An improved process of the novel HMG CoA reductase inhibitor SIPI-4884 has been developed for early preclinical pharmacology and safety studies, and it was made up with an efficient nine-step and scalable process. Significant improvements in the nucleophilic substitution, reduction, Wittig–Horner reaction, and preparation of calcium salt were demonstrated. The overall yield was improved to 17.2%.",10.1021/op400060z,2013-05-24,0.7216301195975733
Organic Process Research & Development,"Process Research and Development of an Enantiomerically Enriched Allyic Amine, One of the Key Intermediates for the Manufacture of Synthetic Tetracyclines","A robust, cost-effective, and high yielding manufacturing process for enantiomerically enriched ( S )-allylic amine 3, a key intermediate for fully synthetic tetracyclines have been developed. Two novel and scalable asymmetric vinylations resulting in high-to-excellent stereoselectivity have been developed for the key step. The final product is purified by an efficient crystallization of a l -tartaric salt. The process described has been used to manufacture ∼350 kg of the tartaric salt of 3 with 99.0% ee in 8 steps (35% overall yield) from cheap and readily available dimethyl maleate.",10.1021/acs.oprd.5b00274,2015-09-30,0.7215897443563769
Journal of Organic Chemistry,Seven-Step Total Synthesis of Sporothriolide,"An enantioselective total synthesis of sporothriolide, a bioactive furofurandione-type fungal metabolite, has been achieved in a 21% overall yield from a commercially available β,γ-unsaturated carboxylic acid via seven steps. The key steps of this synthesis include a highly diastereoselective Michael addition of a chiral oxazolidinone derivative to a nitro olefin, the exploitation of an aromatic ring as a masked carboxylic acid functionality, and the base-promoted elimination of nitrous acid to install the α-methylene lactone unit of sporothriolide in the final step.",10.1021/acs.joc.1c01663,2021-08-23,0.7215823266169887
Organic Process Research & Development,Highly Efficient and Practical Synthesis of the Key Intermediate of Telmisartan,"We reported herein an efficient and practical method to access 1,7′-dimethyl-2′-propyl-2,5′-bi(1 H -benzimidazole) 1, a key intermediate for the synthesis of telmisartan. The synthetic route was based on readily available o -methylaniline as the starting material, and the target product 1 was prepared through a six-step process, including amidation, formylation, cyclization, hydrolysis, amidine, and oxidation. The overall yield for the preparation of 1 was 51.5% on the 100 g scale, with a purity of 99.91%. The salient features of this method include economic and easily available starting materials, operational simplicity, and environmentally friendly, which is suitable for the industrial production.",10.1021/acs.oprd.1c00025,2021-03-17,0.7214030203073982
Organic Process Research & Development,Development of a Large-Scale Route to Glecaprevir: Synthesis of the Side Chain and Final Assembly,"The preceding article described the development of the large-scale synthetic route to macrocycle 3 of glecaprevir ( 1 ), a potent HCV protease inhibitor. This article describes the development of the synthesis of the difluoromethyl-substituted cyclopropyl amino acid 4, its conversion to the fully elaborated side chain, amino sulfonamide 2, and the subsequent final coupling to form glecaprevir. The synthesis of amino acid 4 consists of four key transformations: (a) formation of the difluoromethyl-substituted cyclopropane ring of (±)-diester 15 via Knoevenagel condensation and Corey–Chaykovsky cyclopropanation, (b) diastereoselective hydrolysis of (±)-diester 15 to yield (±)-monoacid 14a – b, (c) conversion of (±)-monoacid 14a – b to (±)-amino ester 10 via a Curtius rearrangement, and (d) resolution of (±)-amino ester 10 followed by saponification to give the desired (1 R,2 R )-amino acid 4 . The large-scale synthetic route to amino acid 4 was successfully used to produce the fully elaborated side chain 2 and ultimately the amount of glecaprevir required to support the late-stage clinical development.",10.1021/acs.oprd.0c00245,2020-07-13,0.7213864950952804
Journal of Organic Chemistry,"Efficient Synthesis of IPL576,092:  A Novel Anti-Asthma Agent","An enantioseletive synthesis of the novel anti-asthma agent IRL576,092 (2) is described. The synthetic route developed involves stereoselective 1,2-reduction of the enone carbonyl functionality of 6 and subsequent hydroboration as the key steps. Starting from the commercially available 5-androsten-3beta-ol-17-one 3, this approach affords IPL576,092 (2) in nine steps with overall yields of 25%, employing a limited number of chromatographic steps.",10.1021/jo0108717,2002-05-01,0.7213708306192154
Journal of Organic Chemistry,"Development of a Scalable Synthesis of a HPK1 Inhibitor Featuring a Direct α-Arylation of Boc-Protected <i>N,N</i>-Dimethylamine by Palladium-Mediated Negishi Cross-Coupling","The development of an improved synthesis of the potent HPK1 inhibitor, compound 1, is described. Two primary strategies were explored during this process: metallaphotoredox decarboxylative coupling and Negishi cross-coupling, both focusing on the direct installation of Boc-protected amine in a single step. Through the optimized Pd-catalyzed Negishi cross-coupling, a robust procedure was established for preparing the compound 9 from 3 in a single step on a 20 g scale. This optimization successfully reduced the overall synthesis steps required to produce 1 from 11 to 6, achieving a 28% overall yield.",10.1021/acs.joc.5c00980,2025-07-18,0.7213386496733659
Journal of the American Chemical Society,Efficient Total Syntheses of Pumiliotoxins A and B. Applications of Iodide-Promoted Iminium Ion−Alkyne Cyclizations in Alkaloid Construction,"A practical route for the total synthesis of pumiliotoxin A alkaloids is described. The central step is formation of the piperidine ring and establishment of the ( Z )-alkylidene side chain by an iodide-promoted iminium ion−alkyne cyclization. The total synthesis of (+)-15( S )-pumiliotoxin A ( 2 ) was realized in 5 steps and 32% overall yield from alkyne 36 and epoxide 7 . This synthesis of 2 proceeded in 13 steps and 12% overall yield from ( S )-2-methyl-1-penten-3-ol ( 25 ) and 8 steps and 9% overall yield from N -[(benzyloxy)carbonyl]- l -proline. The synthesis of (+)-pumiliotoxin B ( 3 ) was similarly achieved in four steps and 44% overall yield from alkyne 54 and epoxide 7 . The overall yield of enantiopure 3 was 8% from N -[(benzyloxy)carbonyl]- l -proline and 10% from (4 S,5 R )-4-methyl-5-phenyl-2-oxazolidinone. These syntheses represent substantial improvement over previous routes to these important alkaloids.",10.1021/ja961641q,1996-01-01,0.7212716851032007
Organic Process Research & Development,Process Research and Development for an Efficient Synthesis of the HIV Protease Inhibitor BMS-232632,"Development of an efficient and scalable process for the human immunodeficiency virus (HIV) protease inhibitor BMS-232632 1-[4-(pyridin-2-yl)phenyl]-5( S )-2,5-bis{[ N -(methoxycarbonyl)- l - tert -leucinyl]-amino}-4( S )-hydroxy-6-phenyl-2-azahexane, is described. The key step in the synthesis of the intermediate N -1-( tert -butyloxycarbonyl)- N -2-[4-(pyridin-2-yl)benzylidene]hydrazone ( 11 ) was the Pd-mediated coupling of boronic acid 9 with 2-bromopyridine. An efficient procedure was developed for the chemoselective reduction of hydrazone 11 to hydrazine carbamate 4 . The key intermediate N -( tert -butyloxycarbonyl)-2( S )-amino-1-phenyl-3( R )-3,4-epoxy-butane ( 6 ) was prepared stereoselectively from chiral diol 10 . The subsequent union of 4 and 6 followed by coupling with N -methoxycarbonyl- l - tert -leucine provided the free base BMS-232632 in high yield. Evaluation of a variety of salts and identification of bisulfate salt 19 with enhanced bioavailability are also described.",10.1021/op025504r,2002-04-20,0.7212440366525228
Organic Process Research & Development,Six-Step Gram-Scale Synthesis of the Human Immunodeficiency Virus Integrase Inhibitor Dolutegravir Sodium,"A short and practical synthesis for preparing the active pharmaceutical ingredient dolutegravir sodium was developed. The convergent strategy starts from ( R )-3-amino-1-butanol and establishes the BC ring system in a 76% isolated yield over four steps. Ring A was constructed by a one-pot 1,4-addition to diethyl-(2 E / Z )-2-(ethoxymethylidene)-3-oxobutandioate and subsequent MgBr 2 ·OEt 2 -mediated regioselective cyclization. Amide formation with 2,4-difluorobenzylamine was either performed from the free carboxylic acid or through aminolysis of the corresponding ethyl ester. Final salt formation afforded dolutegravir sodium in a 48–51% isolated yield (HPLC purity of 99.7–99.9%) over six linear steps.",10.1021/acs.oprd.1c00139,2021-07-12,0.7208526246178915
Journal of Organic Chemistry,Formal Total Synthesis of Salicylihalamides A and B,"An efficient synthesis of the macrolactone 3 of the salicylihalamides in 10 linear steps from alkene 6 is described. The key steps involved a Stille coupling between the chiral stannane 5 and benzyl bromide 4, which produced alkene 15 in good yield, and subsequent base-induced macrolactonization then gave compound 3. Macrolactone 3 was then converted into the known salicylihalamide A intermediate 18 in a three-step sequence. Compound 3 was also converted into another known salicylihalamide A and B intermediate 23 in a five-step sequence.",10.1021/jo026798h,2003-02-13,0.7206686865144255
Tetrahedron,A convergent synthesis of the renin inhibitor CGP60536B,,10.1016/s0040-4039(00)01760-3,2000-12-01,0.7206663668181986
Organic Process Research & Development,"The Development of a Practical and Reliable Large-Scale Synthesis of 2,6-Diamino-4-bromopyridine","A novel, safer, and efficient synthetic route to 2,6-diamino-4-bromopyridine has been developed. In discovery research a five-step synthesis afforded 2,6-diamino-4-bromopyridine in 56% yield with a double Curtius rearrangement as a key transformation. Due to potential safety concerns on larger scale an alternative synthetic strategy was necessary. Starting from 2,4-dibromopyridine- N- oxide two complementary procedures have been developed to access 2,6-diamino-4-bromopyridine. The four-step procedure yielded in 28% overall, and the five-step procedure, in 33% overall 2,6-diamino-4-bromopyridine in a safe and straightforward manner using a regioselective 2,6-diamination reaction as key step. Additionally, a general route to unsymmetrical substituted pyridine N -oxide derivatives is disclosed.",10.1021/op020085j,2002-12-03,0.7206068155620907
Organic Process Research & Development,Efficient Synthesis of a Highly Selective NPY-5 Receptor Antagonist:  A Drug Candidate for the Treatment of Obesity,"A concise and practical synthesis of highly selective NPY-5 receptor antagonist 1 is described. The animopyrazine intermediate 3 was synthesized via either monobromination of aminopyrazine or palladium-catalyzed regioselective debromination of dibromopyrazine followed by an efficient Suzuki−Miyaura coupling. For the preparation of the spirolactone piperidine 2, significantly improved yield was achieved by using a combination of n -BuMgCl and n -BuLi. This protocol also dramatically increased the thermal stability of the aryllithium intermediate and eliminated the requirement for costly cryogenic conditions. The union of the spirolactone piperidine 2 and aminopyrazine 3 via a carbonyl group was accomplished using phenyl chloroformate delivering the target molecule in high yield.",10.1021/op0600963,2006-06-14,0.7205821757959219
Tetrahedron,A practical route to epibatidine,,10.1016/s0040-4039(00)76859-6,1994-05-01,0.7204664576034722
Tetrahedron,Chiral synthesis of a key intermediate in the preparation of the AF toxin IIc,,10.1016/s0040-4039(00)70650-2,1989-01-01,0.720320820284978
Organic Process Research & Development,Development and Large-Scale Preparation of an Oral TACE Inhibitor,"An efficient, expedient synthesis of BMS-561392, 1, which enabled rapid delivery of drug substance for clinical development is described. The key features of the synthesis include an efficient synthesis of a phenolic α,α-disubstituted amino ester via carbon alkylation without protection of the phenol, an effective enzymatic resolution of this racemic amino ester, and a process for the preparation of a hydroxamic acid drug substance with undetectable levels of hydroxylamine.",10.1021/op800308t,2009-03-18,0.7201017331164072
Tetrahedron,Stereo- and regiospecific allylation of 4-chloroazetidinones with allylsilanes: Convergent synthesis of a key intermediate for (+)-thienamycin,,10.1016/s0040-4039(00)87743-6,1982-01-01,0.7200450105131526
Organic Letters,"Total Synthesis of Muricadienin, the Putative Key Precursor in the Solamin Biosynthesis","The first total synthesis of muricadienin, the unsaturated putative precursor in the biosynthesis of trans- and cis-solamin is described. Key steps in the synthesis are a chemoselective hydroboration, a Z-selective Wittig reaction, and a Fries rearrangement for introducing the terminal α-substituted butenolide. Thus, muricadienin can be synthesized in 11 steps from commercially available starting materials in 42% overall yield.",10.1021/ol502849y,2014-11-07,0.7200095677553955
Synlett,Concise Asymmetric Synthesis of Antimalarial Alkaloid (+)-Febrifugine,An asymmetric total synthesis of antimalarial alkaloid (+)-febrifugine is accomplished in 23% overall yield over 14 steps from readily available starting materials. The synthesis features a SmI2-mediated reductive cross-coupling of chiral N-tert-butanesulfinyl imine with aldehyde.,10.1055/s-0029-1217713,2009-07-29,0.720005927230016
Organic Letters,"An Efficient and Highly Diastereoselective Synthesis of GSK1265744, a Potent HIV Integrase Inhibitor","A novel synthesis of GSK1265744, a potent HIV integrase inhibitor, is described. The synthesis is highlighted by an efficient construction of the densely functionalized pyridinone core as well as a highly diastereoselective formation of the acyl oxazolidine moiety. The latter exploits the target molecule's ability to chelate to Mg(2+), a key feature in the integrase inhibitor's mechanism of action.",10.1021/ol503580t,2015-01-23,0.7198877836406888
Organic Process Research & Development,Two Approaches to the Chemical Development and Large-Scale Preparation of a Pyrimidyl Tetrazole Intermediate,"Two new routes to a pyrimidyl tetrazole intermediate are described. The first-generation route featured an iron-catalyzed cross-coupling between 4-butenylmagnesium bromide and a 4-chloropyrimidine derivative to afford an alkene-bearing pyrimidine intermediate. A subsequent intramolecular Heck cyclization afforded the desired bicyclic core, which was subsequently converted to the corresponding carboxylic acid via hydroboration and oxidation. This route was rapidly defined and used to prepare the initial 0.3 kg of the pyrimidyl tetrazole intermediate, which supported early toxicology and clinical studies of a drug candidate. A second-generation, eight-step route to the pyrimidyl tetrazole intermediate was defined and demonstrated on multikilogram scale in a 21% overall yield. The key transformation in this sequence was a copper(I) mediated cyclization of an iodopyrimidine, affording the bicyclic core of the target in quantitative yield. Due to the larger scale involved for the second-generation approach, significant process safety evaluation was undertaken for a number of steps in this route, and the highlights of these studies are presented.",10.1021/acs.oprd.6b00136,2016-06-08,0.719874334679186
Organic Process Research & Development,Diastereoselective Reaction of a Grignard Reagent with Chiral Imides:  A Practical Preparation of a Key Intermediate in the Synthesis of Ifetroban Sodium,"A novel and highly efficient synthesis of [1 S -(1α,2α,3α,4α)]-2-[[2-(3-methoxy-3-oxopropyl)phenyl]methyl]-7-oxabicyclo[2.2.1]heptane-3-carboxylic acid ( A ), a key intermediate in the synthesis of ifetroban sodium, BMS-180291, is described. Reaction of chiral imides such as [2( S ),3aα,4β,7β,7aα]-hexahydro-2-(1-phenylethyl)-4,7-epoxy-1 H -isoindole-1,3(2 H )-dione ( B ) with the Grignard reagent derived from 2-(2-bromophenyl)-1,3-dioxolane and subsequent in situ transformations give [2 S -(2α,3aα,4β,7β,7aα)]-2-(octahydro-3-oxo-4,7-epoxyisobenzofuran-1-yl)benzaldehyde, converted in two steps to A . Efficient syntheses of B from furan and maleic anhydride are described.",10.1021/op960034k,1997-01-01,0.7197454671917681
Organic Process Research & Development,Route Design and Development of a MET Kinase Inhibitor: A Copper-Catalyzed Preparation of an <i>N</i>1<i>-</i>Methylindazole,"The synthesis of a MET kinase inhibitor in an overall yield of 22% was achieved over eight steps starting with 3-hydroxybenzaldehyde, an improvement from the initial 12-step process with a 5.4% yield. Highlights of the process chemistry design and development are a Cu-catalyzed cyclization to form an important N 1-methylindazole ring, a selective nitro reduction in the presence of an aryl bromide, a late-stage Suzuki cross-coupling, and a base-promoted Boc deprotection to form the desired drug candidate.",10.1021/op400317z,2014-03-03,0.7196409148068541
Organic Process Research & Development,Process Improvements of Prasugrel Hydrochloride: An Adenosine Diphosphate Receptor Antagonist,"An improved process for the synthesis of prasugrel hydrochloride with an overall yield of 58%, 99.9% purity, and meeting all other quality requirements is described.",10.1021/op200325u,2012-01-06,0.7196317627637628
Organic Process Research & Development,Development of a Scalable Synthesis of the Small Molecule TGFβR1 Inhibitor <b>BMS-986260</b>,"A scalable route to the small molecule TGFβR1 inhibitor BMS-986260 ( 1 ) was developed. This alternative approach circumvented the purification of intermediates by column chromatography and provided access to multikilogram quantities of the key intermediate, 6 . The safety aspects of the synthetic approach to the other fragment of the API (TosMIC 10 ) were critically evaluated, and a robust process for its large-scale synthesis was successfully demonstrated.",10.1021/acs.oprd.0c00232,2020-07-02,0.719535568970593
Organic Process Research & Development,Process Research for Multikilogram Production of Etamicastat: A Novel Dopamine β-Hydroxylase Inhibitor,"In order to develop a manufacturing route to etamicastat, three synthetic approaches to the pivotal chiral 3-aminochroman intermediate have been studied as well as four methods for the construction of the 2-aminoethyl imidazolethione fragment. The evolution of the synthetic strategy based on the early discovery route was described. By focusing on the use of readily available starting materials it was possible to avoid chromatography steps and expensive reagents, bringing about significant improvements in cost and throughput. The best route involves construction of the chiral centre by asymmetric hydrogenation.",10.1021/op300012d,2012-03-01,0.7194963589849159
Tetrahedron,"Bioactive marine metabolites XII. Moritoside, an inhibitor of the development of starfish embryo, from the gorgonian sp.",,10.1016/s0040-4039(00)99024-5,1985-01-01,0.71942890892323
Organic Process Research & Development,Development of an Efficient Synthetic Process for Broflanilide,"This article describes the development of an efficient and scalable synthetic route to the novel insecticide broflanilide ( 1 ). This redesigned synthetic sequence starts from 2-fluoro-3-nitrobenzoic acid and 4-(perfluoropropan-2-yl)-2-(trifluoromethyl) aniline and provides the target product in a high overall yield through condensation, nitro group reduction, N -methylation, amidation, and subsequent bromination steps. The desired amide moiety is established under mild conditions, and imide generation is avoided. Using paraformaldehyde and Pt/C for N -methylation and NaBr-NaClO for bromination increased the industrial suitability of this route. Unlike existing routes, this new route requires isolation at only six steps (including the heptafluorination), and the overall yield was 60.3%, representing a significant improvement. Broflanilide ( 1 ) crystals were obtained from recrystallization in 98% aqueous CH 3 OH, and the structure was confirmed by X-ray analysis. This work provides a reliable strategy for the large-scale manufacturing of broflanilide ( 1 ).",10.1021/acs.oprd.0c00028,2020-04-07,0.7193827203093541
Synlett,"Asymmetric Synthesis of 4,5-Disubstituted 3-Hydroxy δ-Lactones: Prelactone B and Prelactone V","An efficient asymmetric synthesis of δ-lactones such as prelactone B has been developed. As key steps, the SAMP/RAMP-hydrazone methodology for the synthesis of 2-methylenated 1,3-diols and a homogenous hydrogenation were used.",10.1055/s-2003-42060,2003-01-01,0.7193058763731248
Organic Letters,"Enantioselective, Biocatalytic Reduction of 3-Substituted Cyclopentenones: Application to the Asymmetric Synthesis of an hNK-1 Receptor Antagonist","A convergent and enantioselective route to the hNK-1 receptor antagonist (1) is described, which sets all six stereogenic centers with high diastereoselectivity and delivers 1 in only 11 steps and 23% overall yield. The process was enabled by the development of the enantioselective enzymatic reduction of 3-functionalized cyclopentenones and stereospecific Pd-catalyzed etherification coupling of fragments 6 and 7.",10.1021/ol1030348,2011-02-08,0.719263334635605
Tetrahedron,Ionophore synthesis. An enantioselective route to the left-wing of indanomycin (X- 14547A).,,10.1016/s0040-4039(00)98423-5,1985-01-01,0.7192154863221419
Organic Process Research & Development,Development of a New Practical Synthesis of a 5-HT<sub>2C</sub> Receptor Agonist,"A new practical synthesis of a 5-HT 2C receptor agonist has been developed and implemented on multikilogram scale. The key step, the selective epoxide opening in the glycidyl tosylate with the aryl Grignard reagent, allowed the incorporation of this commercially available chiral C 3 synthon into the molecule and elaboration of the resulting intermediate into the target aminomethyldihydrobenzofuran without loss of enantiomeric purity.",10.1021/op100233f,2010-11-02,0.7191240967101555
Organic Process Research & Development,Some Items of Interest to Process R&amp;D Chemists and Engineers,"Overexpression of the chemokine CXCR3 receptor has been linked to several autoimmune disorders including psoriasis, rheumatoid arthritis and multiple sclerosis.Two practical synthetic routes to a pyrido[2,3-d]-pyrimidine-based inhibitor of the CXCR3 receptor are described by Chan, Burke, and co-workers at Amgen (J.Org.Chem.2011, 76, 1767À1774).The first synthesis, which begins with racemic starting materials, constructs the pyrido[2,3d]pyrimidine cores from a 2-amino nicotinamide and triethyl orthopropionate.Selective functionalization (chlorination) of an ethyl moiety of pyrido [2,3-d]pyrimidine provided access to the requisite primary amine in four steps and 72% overall yield.Furthermore, a classical resolution of this primary amine using a tartaric acid derivative was developed and implemented at 5 kg scale.The sulfone-containing aldehyde used for end-game reductive amination was secured in practical fashion via a crystalline bisulfite adduct.Lastly, a CDI-mediated coupling to form the final amide bond afforded the API and replaced the existing EDC HCl conditions.In an alternative scheme the amine-bearing stereocenter is derived from the readily available enantiopure building block (D)alanine.This approach makes use of a challenging CÀN coupling reaction that allowed use of 2-chloronicotinic acid as a cheaper alternative to 2-aminonicotinic acid.By preserving the stereocenter through the isopropylmagnesium chloride-mediated amide bond formation with 4-chloroaniline and the subsequent dehydrative cyclization and Boc group cleavage, the key amine intermediate was accessed in enantioenriched form without the need for a resolution.This second synthesis, thus far performed at gram scale, intersects the former route at a common intermediate and demonstrates a potentially more effective route for future API deliveries.",10.1021/op2000942,2011-05-03,0.7190990390049876
Organic Process Research & Development,An Efficient Through-Process for Chk1 Kinase Inhibitor GDC-0575,"We report an efficient route to prepare Chk1 kinase inhibitor GDC-0575 from 5-bromo-4-chloro-3-nitro-7-azaindole featuring a sequence of nucleophilic aromatic substitution, hydrogenative nitro-reduction, and a robust, high-yielding end-game involving deprotection–crystallization steps. The developed route was demonstrated on 10 kg scale in 30% overall yield to provide the target API in >99.8 A % HPLC purity.",10.1021/acs.oprd.7b00388,2018-02-08,0.7190475553068154
European Journal of Organic Chemistry,Total Synthesis of Indolizidine (+)‐223A,"Abstract We described the diastereoselective total synthesis of indolizidine (+)‐223A in 10 % overall yield over 14 steps starting from 6‐chlorohex‐2‐ynoate. Our strategy involved chain elongation through aldolization, the formation of the indolizidine skeleton by cyclization, and stereocontrolled hydrogenation.",10.1002/ejoc.201101530,2011-12-07,0.7189768429563769
Tetrahedron,A simple route to a key intermediate for the synthesis of 11-desoxyprostaglandins,,10.1016/s0040-4039(01)87545-6,1971-01-01,0.7189506407286976
Organic Letters,Enantioselective Synthesis of a Dual Orexin Receptor Antagonist,"A concise, enantioselective synthesis of the potent dual orexin inhibitor suvorexant (1) is reported. Key features of the synthesis include a mild copper-catalyzed amination, a highly chemoselective conjugate addition, and a tandem enantioselective transamination/seven-membered ring annulation. The synthesis requires inexpensive starting materials and only four linear steps for completion.",10.1021/ol3014123,2012-06-22,0.7189397653337296
Tetrahedron,"A novel route from triptycenes to a dibenzo(Hafner's hydrocarbon), benz[a]indeno[1,2,3-cd]azulene",,10.1016/s0040-4039(00)71407-9,1980-01-01,0.7187388940950445
Tetrahedron,The sulfhydrolysis of dialkoxycarbonium ions. A novel route to thionesters,,10.1016/s0040-4039(01)85814-7,1978-01-01,0.7187388940950445
Tetrahedron,A novel route to cyclopropanes from olefins,,10.1016/s0040-4039(01)82791-x,1966-01-01,0.7187388940950445
Tetrahedron,A novel route to monoanomeric spiroketals,,10.1016/s0040-4039(98)00685-6,1998-06-01,0.7187388940950445
Tetrahedron,"Pyrolysis of 2-azidoaryl thioketones: A novel route to 2,1-benzisothiazoles",,10.1016/s0040-4039(01)96696-1,1971-01-01,0.7187388940950445
Tetrahedron,A novel route to tetracyclic hydroxyquinones,,10.1016/s0040-4039(01)84712-2,1972-01-01,0.7187388940950445
Tetrahedron,A novel π-route to the 7-norbornenyl cation,,10.1016/s0040-4039(01)82559-4,1974-01-01,0.7187388940950445
Journal of Organic Chemistry,Highly Efficient Stereocontrolled Synthesis of Danishefsky’s Taxol CD Ring Key Intermediate,Danishefsky's taxol CD ring key intermediate is synthesized in 15 steps and 11.4% overall yield from a readily available starting material. Absolute stereochemistry of the starting material and stereocontrolled steps determine the absolute configuration of the five requisite contiguous stereocenters.,10.1021/jo800913x,2008-06-18,0.7187045810734909
Organic Process Research & Development,New Synthetic Route to a Dipeptidyl Peptidase-4 Inhibitor,"A new synthetic route to a dipeptidyl peptidase-4 (DPP4) inhibitor was developed and demonstrated on a multigram scale. This approach takes advantage of the cheap and readily available Boc- trans -4-hydroxy- l -proline methyl ester as starting material which was derivatized through an S N 2 reaction. Several leaving groups were studied, and the nosylate group showed superiority over other derivatives. Formation of an amide using the most costly starting material, 3,3-difluoropyrrolidine, was performed late in the synthesis to minimize its economical impact on the overall cost of the API.",10.1021/op200309z,2012-01-28,0.7186921409217154
Tetrahedron,An efficient synthesis of a key intermediate for the preparation of the rhinovirus protease inhibitor AG7088 via asymmetric dianionic cyanomethylation of N-Boc-l-(+)-glutamic acid dimethyl ester,,10.1016/s0040-4039(01)01416-2,2001-09-01,0.7186408145266101
Tetrahedron,"Efficient route to the synthesis of C-2, C-3 substituted 4-piperidones",,10.1016/s0040-4039(00)79755-3,1991-07-01,0.7184977894491513
Organic Process Research & Development,Synthesis of BACE Inhibitor LY2886721. Part I. An Asymmetric Nitrone Cycloaddition Strategy,"A scalable, asymmetric synthesis of (3 aS,6 aS )-6 a -(5-bromo-2-fluorophenyl)-1-(( R )-1-phenylpropyl)tetrahydro-1 H,3 H -furo[3,4- c ]isoxazole, a key intermediate in the synthesis of LY2886721, is reported. Highlights of the synthesis include the development of an asymmetric [3 + 2] intramolecular cycloaddition facilitated by trifluoroethanol, and the development of a new synthesis of ( R )- N -(1-phenylpropyl)hydroxylamine tosylate which proceeds through a p -anisaldehyde imine and avoids the formation of toxic hydrogen cyanide gas as a byproduct. The synthesis proceeds over four steps and provides the product in 36% overall yield.",10.1021/op500351q,2015-09-04,0.7183308529843412
Synlett,A Formal Enantioselective Synthesis of (–)-Epiquinamide by Proline-Catalyzed One-Pot Sequential α-Amination/Propargylation of Aldehyde and Asymmetric Dihydroxylation of Olefin,"Two independent routes to the formal synthesis of (–)-epiquinamide, have been described: the first route utilizes an l -proline-catalyzed one-pot sequential α-amination/propargylation of aldehyde, while the second one employs asymmetric dihydroxylation as the key reaction to install the stereochemistry. While the first synthesis was accomplished in nine steps with 24.4% overall yield and dr 9:1, the second strategy resulted in the synthesis in eight steps with 36.4% overall yield and with perfect enantiocontrol.",10.1055/s-0035-1561956,2016-04-07,0.7180468189167324
Organic Process Research & Development,"AMD070, a CXCR4 Chemokine Receptor Antagonist: Practical Large-Scale Laboratory Synthesis",An efficient and convergent four-step synthetic route to the CXCR4 chemokine receptor antagonist AMD070 ( 1 ) has been developed which employs only a single chromatographic step in the entire sequence. Novel reductive amination methods have been developed for the coupling of 2 and 3 in which a dehydrative imine formation is followed by reduction with an attenuated borohydride reagent (zinc chloride and sodium borohydride). Selective extraction methods were employed to purify synthetic intermediates and remove reagents and impurities. A procedure has also been developed to isolate 1 in a pure crystalline form.,10.1021/op8000993,2008-07-18,0.7180016387328905
Journal of Organic Chemistry,Total Synthesis of the Depsipeptide FR-901375,"The first total synthesis of FR-901375, a novel bicyclic depsipeptide isolated from the fermentation broth of Pseudomonas chloroaphis No. 2522, has been achieved. The synthetic approach involves 13 reaction steps and is achieved in 12% overall yield. The key points in the successful synthetic strategy are a concise asymmetric synthesis of the key building block (3R,4E)-3-hydroxy-7-mercapto-4-heptenoic acid, a mild Mitsunobu macrolactonization step, and an I(2)-mediated deprotection with concomitant disulfide-bridge formation.",10.1021/jo034765b,2003-10-15,0.7179808505419861
Synlett,Total Synthesis of Luteoalbusin A and Formal Synthesis of T988 C,"An efficient total synthesis of luteoalbusin A was achieved in nine linear steps and in 17% overall yield from the known and easily accessible 3a-(3-indolyl)-hexahydropyrrolo[2,3-b]indole. A formal synthesis of (+)-T988 C through manipulation of the key intermediate is also reported.",10.1055/s-0036-1591880,2018-01-19,0.7179162856815043
Organic Letters,"Development of a Concise, Asymmetric Synthesis of a Smoothened Receptor (SMO) Inhibitor: Enzymatic Transamination of a 4-Piperidinone with Dynamic Kinetic Resolution","A concise, asymmetric synthesis of a smoothened receptor inhibitor (1) is described. The synthesis features an enzymatic transamination with concurrent dynamic kinetic resolution (DKR) of a 4-piperidone (4) to establish the two stereogenic centers required in a single step. This efficient reaction affords the desired anti amine (3) in >10:1 dr and >99% ee. The title compound is prepared in only five steps with 40% overall yield.",10.1021/ol403630g,2014-01-22,0.7178374353783077
Journal of Organic Chemistry,Stereoselective Synthesis of (<i>S</i>)-3-(Methylamino)-3-((<i>R</i>)-pyrrolidin-3-yl)propanenitrile,"(S)-3-(methylamino)-3-((R)-pyrrolidin-3-yl)propanenitrile (1) is a key intermediate in the preparation of PF-00951966, (1) a fluoroquinolone antibiotic for use against key pathogens causing community-acquired respiratory tract infections including multidrug resistant (MDR) organisms. The current work describes the development of a highly efficient and stereoselective synthesis of 1 in 10 steps with an overall yield of 24% from readily available benzyloxyacetyl chloride. Two key transformations in the synthetic sequence involve (a) catalytic asymmetric hydrogenation with chiral DM-SEGPHOS-Ru(II) complex to afford β-hydroxy amide 11b in good yield (73%) and high stereoselectivity (de 98%, ee >99%) after recrystallization and (b) S(N)2 substitution reaction with methylamine to provide diamine 14 with inversion of configuration at the 1'-position in high yield (80%), after efficient purification using a simple acid/base extraction protocol.",10.1021/jo3004716,2012-04-23,0.717814837932579
Synlett,First Total Synthesis of Murrastifoline B and an Improved Route to Murrastifoline F,We report the first total synthesis of murrastifoline B and an improved route to murrastifoline F using a twofold palladium-catalyzed Buchwald–Hartwig amination as key step. The mono­meric carbazole and the biaryl precursor are also prepared via ­palladium-catalyzed coupling reactions.,10.1055/s-0033-1338621,2014-04-03,0.7176511861541109
Organic Process Research & Development,"Development of a Scaleable Synthesis of NDT 9533750, a Key Intermediate to a Series of Novel Subtype Preferring GABA<sub>A</sub> Partial Agonists","A scaleable route to 6-chloro-4-[2-(3-fluoropyridin-2-yl)-imidazol-1-ylmethyl]-5-propyl-pyrimidine (NDT 9533750), a key intermediate to a series of novel subtype preferring GABA A partial agonists, is described in which various scaleup issues were addressed to provide an efficient and robust route for the preparation of kilogram quantities of the compound.",10.1021/op700084h,2007-06-27,0.7174645936113261
Journal of Organic Chemistry,A Very Efficient Route toward the 4a-Methyltetrahydrofluorene Skeleton: Short Synthesis of (±)-Dichroanone and (±)-Taiwaniaquinone H,"A very expedient and efficient new route toward taiwaniaquinoids, bearing the 4a-methyltetrahydrofluorene skeleton, is reported. Key steps are the intramolecular Friedel-Crafts alkylation of an aryldiene and the degradative oxidation of a methylenedioxy group; the latter process could also be utilized for building the 2-hydroxy-1,4-benzoquinone unit, which is frequently found in natural products. Utilizing this new methodology, (+/-)-dichroanone (7) (three steps, 77% overall yield) and (+/-)-taiwaniaquinone H (6) (four steps, 70% overall yield) have been synthesized from commercial alpha- (11a) or beta-cyclocitral (11b).",10.1021/jo900153y,2009-04-06,0.7174345348905732
Synlett,Toward the Total Syntheses of Pepluanin A and Euphosalicin: Concise Route to a Highly Oxygenated Cyclopentane as a Common Intermediate,"A substrate controlled asymmetric synthesis is described of a highly functionalized cyclopentanyl vinyl triflate which serves as an advanced intermediate in the total synthesis of the novel multidrug resistance reversing jatrophanes pepluanin A and euphosalicin. Key steps are a Claisen-Eschenmoser rearrangement followed by hydroxy-lactonization, intramolecular trans-lactonization, Davis hydroxylation and regioselective enoltriflate formation.",10.1055/s-2004-834822,2004-10-20,0.7173801578890387
Organic Process Research & Development,"Development of a Manufacturing Process for Sibenadet Hydrochloride, the Active Ingredient of Viozan","A process for commercial manufacture of the dual D 2 -β 2 receptor agonist sibenadet hydrochloride has been developed. The process relies upon introduction of operationally simple chemistry at the final stages where two key intermediates are reacted to assemble the final molecule, isolated by crystallization. A nine-stage sequence for synthesis of the key amine hydrochloride intermediate was developed, and modifications to the original process are described. Major strategic improvements were made in definition of the final route to the “side chain” precursor molecule, the second key intermediate, hinging around a thiyl radical addition and subsequent high-yielding telescoped processes for synthesis of this highly crystalline benzoate ester. Development of these chemistries is discussed, together with some issues surrounding definition of the final validated commercial processes.",10.1021/op049953y,2004-06-16,0.717354141667817
Journal of Organic Chemistry,"Palladium-Catalyzed Regioselective Arylation of Imidazo[1,2-<i>b</i>][1,2,4]triazine:  Synthesis of an α<sub>2/</sub><sub>3</sub>-Selective GABA Agonist","A convergent, practical, and efficient synthesis of 2',6-difluoro-5'-[3-(1-hydroxy-1-methylethyl)imidazo[1,2-b][1,2,4]triazin-7-yl]biphenyl-2-carbonitrile (1), an orally active GABA(A) alpha(2/3)-selective agonist, is described. The seven-step, chromatography-free synthesis was demonstrated on a multi-kilogram scale and utilized biaryl bromide 6 and imidazotriazine 22 as key intermediates. Biaryl bromide 6 was prepared via a highly selective aromatic bromination. The regioselective condensation of aminotriazine 15 with chloroacetaldehyde provided the desired imidazotriazine intermediate 22. A highly regioselective palladium-catalyzed arylation in the final step highlights the efficiency of the route.",10.1021/jo0507035,2005-06-24,0.717272954892076
Journal of Organic Chemistry,Large Scale Synthesis of 2′-Amino-LNA Thymine and 5-Methylcytosine Nucleosides,"Thymine intermediate 17 has been synthesized on a multigram scale (50 g, 70 mmol) from starting sugar 1 in 15 steps in an overall yield of 73%, with only 5 purification steps. The key thymine intermediate 18 was obtained from 17 in a single step in 96% yield, whereas the key 5-methylcytosine intermediate 20 was obtained from 17 in 2 steps in 58% yield. This highly efficient large scale route necessitates only 2 and 3 novel steps to obtain N2'-functionalized thymine and 5-methylcytosine amino-LNA phosphoramidites from these key intermediates, respectively.",10.1021/jo302036h,2012-11-12,0.7171607422091825
Journal of the American Chemical Society,Enantioselective Synthesis of N1999A2,"An enantioselective synthetic route to the enediyne antibiotic N1999A2 (1) is described, proceeding in 21 steps (0.4% yield, 77% average yield per step) from (R)-(+)-glycidol. The route involves the convergent assembly of three components: a (1-iodovinyl) stannane (2), a 1,5-hexadiyne-3,4-diol derivative (3), and a substituted naphthoic acid (4). Important transformations in the synthetic sequence include the palladium-catalyzed coupling of 2 and 3, an intramolecular oxidative cyclization of a terminal bisacetylene, and a transannular anionic (bi)cyclization of a cyclic bromoenetriyne. The careful selection and manipulation of protective groups throughout the sequence proved to be critical to the development of the synthetic route, where all late-stage intermediates were unstable and could not be concentrated. In the final step of the sequence, three protective groups were removed in a single operation, providing synthetic N1999A2 (1) in 76% yield. Conditions were found that, for the first time, led to the precipitation of 1 as a solid.",10.1021/ja0662467,2006-10-27,0.7171522052574091
Synthesis,"Photolysis of 2,2'-Dinitrodiphenylmethanes. A New Route to the Dibenzo[<i>c,f</i>][1,2]diazepine System",,10.1055/s-1974-23460,1974-01-01,0.7171404499440378
Tetrahedron,"A new route to 1,1-difluoroolefins",,10.1016/s0040-4039(97)01363-4,1997-08-01,0.7171404499440378
Tetrahedron,A new route to linearly fused polyquinanes,,10.1016/s0040-4039(00)98030-4,1990-01-01,0.7171404499440378
Tetrahedron,A new enantiospecific route to the pseudopterosins,,10.1016/s0040-4039(00)97487-2,1990-01-01,0.7171404499440378
Synthesis,A New Route to Tryptamines,,10.1055/s-1974-25325,1974-01-01,0.7171404499440378
Tetrahedron,A new route to tropanes,,10.1016/s0040-4039(01)82403-5,1974-01-01,0.7171404499440378
Tetrahedron,A new route to the metacyclophane system,,10.1016/s0040-4039(00)73053-x,1994-03-01,0.7171404499440378
Tetrahedron,The photochemistry of proaporphines: a new route to the aporphines,,10.1016/s0040-4039(00)71456-0,1980-01-01,0.7171404499440378
Tetrahedron,"A new route to cyclopentane-1,3-diones",,10.1016/s0040-4039(00)84477-9,1986-01-01,0.7171404499440378
Tetrahedron,"Iodocyclisation of unsaturated lactols and acetals. A new route to furo-2,3b-furans and pyrans.",,10.1016/s0040-4039(00)85514-8,1986-01-01,0.7171404499440378
Tetrahedron,A new route to oligodeoxynucleoside phosphoramidates (PNH2),,10.1016/s0040-4039(97)01153-2,1997-07-01,0.7171404499440378
Tetrahedron,Thermolysis of -(-azidobenzoyl)-iminopyridinium ylide: a new route to 3-indazol-3-one,,10.1016/s0040-4039(01)80926-6,1985-01-01,0.7171404499440378
Tetrahedron,New route to (3RS) (5R) (5-2H)- and (3RS) (5S) (5-2H)-mevalonolactones,,10.1016/s0040-4039(00)96284-1,1987-01-01,0.7171404499440378
Tetrahedron,A new route towards N-(α-methoxybenzyl)aziridines,,10.1016/s0040-4039(02)02838-1,2003-02-01,0.7171404499440378
Tetrahedron,A new (3+3) annulation route to isoquinoline-3-carboxylates,,10.1016/s0040-4039(02)01000-6,2002-07-01,0.7171404499440378
Tetrahedron,A new route to penems and carbapenems,,10.1016/s0040-4039(01)80264-1,1984-01-01,0.7171404499440378
Synthesis,"A New Route to 2,4,6-Triarylpyridines via Stabilized Sulfuranes",,10.1055/s-1981-29433,1981-01-01,0.7171404499440378
Tetrahedron,A new route to sulfonium ylides. Diphenylsulfonium isopbopylide,,10.1016/s0040-4039(00)90822-0,1967-01-01,0.7171404499440378
Synthesis,"A New Route to 1,8-Diphenylcyclooctatetraene",,10.1055/s-1982-30019,2002-05-15,0.7171404499440378
Tetrahedron,A new route to alkenylcyclobutenes,,10.1016/j.tetlet.2008.08.085,2008-08-29,0.7171404499440378
Tetrahedron,A new route to 2-spiropiperidines,,10.1016/s0040-4039(01)00881-4,2001-07-01,0.7171404499440378
Tetrahedron,Desilylation of α-trimethylsilylmethylene-δ-lactones. A new route to α-methylene-δ-lactones,,10.1016/s0040-4039(00)86117-1,1988-01-01,0.7171404499440378
Tetrahedron,A new route to methylenimine via pyrolysis of azetidine,,10.1016/s0040-4039(01)85336-3,1978-01-01,0.7171404499440378
Tetrahedron,A new route to phenazines,,10.1016/s0040-4039(99)02061-4,2000-01-01,0.7171404499440378
Tetrahedron,Isobullatenone and a demethylated analog. A new route to 3(2H) furanones.,,10.1016/s0040-4039(01)85019-x,1972-01-01,0.7171404499440378
Tetrahedron,A new route to 6-deoxy-6-halo sugars,,10.1016/s0040-4039(01)98269-3,1970-01-01,0.7171404499440378
Synthesis,A New Route to<i>sec</i>-Alkanephosphonates,,10.1055/s-1977-24311,1977-01-01,0.7171404499440378
Synthesis,"New Route to α,β-Unsaturated Phosphonates",,10.1055/s-1973-22220,1973-01-01,0.7171404499440378
Tetrahedron,A new route to cevimeline,,10.1016/j.tetlet.2013.03.090,2013-04-06,0.7171404499440378
Tetrahedron,A new route to azocines,,10.1016/s0040-4039(01)98096-7,1970-01-01,0.7171404499440378
Tetrahedron,Silyl-cupration of allene. A new route to silylated synthons,,10.1016/s0040-4039(00)82054-7,1988-01-01,0.7171404499440378
Tetrahedron,A new route to 3-methylenecephams,,10.1016/s0040-4039(01)94897-x,1978-01-01,0.7171404499440378
Tetrahedron,"A new route to cyclen, cyclam and homocyclen",,10.1016/s0040-4039(98)01497-x,1998-09-01,0.7171404499440378
Synthesis,A New Route to Symmetric Diarylnitroxyls,,10.1055/s-1983-30514,1983-01-01,0.7171404499440378
Tetrahedron,A new route to homochiral piperidines,,10.1016/s0040-4039(00)73744-0,1993-09-01,0.7171404499440378
Tetrahedron,"A new route to 2,2′,3,3′-tetrasubstituted binaphthyls",,10.1016/j.tetlet.2009.03.008,2009-03-10,0.7171404499440378
Tetrahedron,A new route to α-methylene lactones,,10.1016/s0040-4039(01)82224-3,1974-01-01,0.7171404499440378
Synthesis,A New Route to Annulated Furans,,10.1055/s-1980-28982,1980-01-01,0.7171404499440378
Tetrahedron,Indirect hydroxylation of phenols: a new route to hydroquinones,,10.1016/s0040-4039(01)82900-2,1981-01-01,0.7171404499440378
Organic Process Research & Development,First-Generation Asymmetric Synthesis of the Selective Estrogen Receptor Degrader GDC-9545 (Giredestrant) Featuring a Highly Efficient Pictet–Spengler Reaction and a C–N Coupling Reaction,"An asymmetric synthesis of the selective estrogen receptor degrader GDC-9545 ( 1 ) is described. The synthesis features a Friedel–Crafts indole functionalization and a strain-release aminoazetidine formation to construct the two key starting materials 2 and 4, respectively, a diastereoselective Pictet–Spengler reaction (98% yield, 95:5 dr) to assemble the tetrahydrocarboline core, and a highly efficient Pd-catalyzed C–N coupling (90% yield) using [ t -BuBrettPhos Pd(allyl)]OTf as the catalyst and DBU as the base to furnish the final C–N bond. This expedient route produces GDC-9545·tartrate active pharmaceutical ingredient in a longest linear sequence of six steps in 37% overall yield with 99.0 area % HPLC purity without chromatographic purification.",10.1021/acs.oprd.1c00262,2021-11-05,0.7171188644882155
Journal of Organic Chemistry,"Synthesis of a Muscarinic Receptor Antagonist via a Diastereoselective Michael Reaction, Selective Deoxyfluorination and Aromatic Metal−Halogen Exchange Reaction","An efficient synthesis of a structurally unique, novel M(3) antagonist 1 is described. Compound 1 is conveniently disconnected retrosynthetically at the amide bond to reveal the acid portion 2 and the amine fragment 3. The synthesis of key intermediate 2 is highlighted by a ZnCl(2)-MAEP complex 19 catalyzed diastereoselective Michael reaction of dioxolane 7 with 2-cyclopenten-1-one (5) to establish the contiguous quaternary-tertiary chiral centers and a subsequent geminal difluorination of ketone 17 using Deoxofluor in the presence of catalytic BF(3).OEt(2). The synthesis of the amine moiety 3 is highlighted by the discovery of a novel n-Bu(3)MgLi magnesium-halogen exchange reaction for selective functionalization of 2,6-dibromopyridine. This new and practical metalation protocol obviated cryogenic conditions and upon quenching with DMF gave 6-bromo-2-formylpyridine (26) in excellent yield. Further transformations afforded the amine fragment 3 via reductive amination with 35, Pd-catalyzed aromatic amination, and deprotection. Finally, the highly convergent synthesis of 1 was accomplished by coupling of the two fragments. This synthesis has been used to prepare multi-kilogram quantities of the bulk drug.",10.1021/jo0157425,2001-09-07,0.7170741159108002
Journal of the American Chemical Society,An Expeditious Synthesis of the MDM2–p53 Inhibitor AM-8553,"The development of the structurally complex MDM2/p53 inhibitor AM-8553 was impeded by the low yield of the initial synthesis. A second generation synthesis is described that features a Noyori dynamic kinetic resolution, a highly diastereoselective allylation, and a novel oxazoline-assisted piperidinone forming reaction to provide AM-8553 in 35.6% yield and 11 steps.",10.1021/ja305123v,2012-06-27,0.7170518209154364
Angewandte Chemie International Edition,Asymmetric Total Synthesis of the Immunosuppressant (−)‐Pironetin,"A short, enantioselective total synthesis of the title compound 1 is described. The 14-step synthesis features a highly stereoselective Brown-type pentenylation and a one-pot hydrosilylation/ring-closing metathesis (RCM)/protodesilylation sequence as the key steps. PG=protecting group.",10.1002/anie.200802423,2008-11-21,0.716823959258684
Organic Process Research & Development,Process Development of a GCS Inhibitor Including Demonstration of Lossen Rearrangement on Kilogram Scale,"A small molecule was under investigation as an inhibitor of glucosylceramide synthase (GCS) for potential use in Fabry disease. To support preclinical activities, a four-step synthesis was developed and used to prepared kilogram quantities of the drug substance. The new route features a scalable CDI-mediated Lossen rearrangement as a substitution for hazardous azide chemistry that was employed in the original route.",10.1021/op500379a,2015-04-02,0.7167031080720359
Organic Process Research & Development,Route Optimization and Manufacture of Multihundred Grams of a Ghrelin Receptor Agonist,"A linear 14-step sequence was developed for the synthesis of an oxaspirocyclic cyclopentane-based candidate drug 1 containing four chiral centers. Compared with the first-generation synthesis with an overall yield of 0.7%, which also included several chromatographic purifications, the large-scale approach furnished >800 g of API 1 in 19% overall yield, and chromatography was avoided in all but two steps. The major achievements were the development of a Curtius rearrangement where hazards were minimized, a robust and safer dose-controlled allylzinc addition to a ketone, and a selective monohydrolysis of a diester.",10.1021/acs.oprd.8b00179,2018-09-05,0.7166356228903419
Organic Process Research & Development,Process Development and Multikilogram Syntheses of XL228 Utilizing a Regioselective Isoxazole Formation and a Selective S<sub>N</sub>Ar Reaction to a Pyrimidine Core,"Route scouting, process development, and multikilogram syntheses of an IGF-1R/Src/Bcr-Abl inihibitor are reported. Key aspects of the developed route are a regioselective [3 + 2] isoxazole formation on a pyrimidine core and a selective S N Ar addition of an aryl amine to a symmetrical dichloro substituted pyrimidine. The route contains six synthetic steps and was demonstrated twice on scale, delivering 4.6 and 11.2 kg (25% and 16% overall yield), for Phase I clinical studies.",10.1021/op400137m,2013-08-06,0.7165784315342006
Organic Process Research & Development,Process Research on the Synthesis of Silthiofam:  A Novel Fungicide for Wheat,"The development of an efficient, low-cost synthesis of the novel wheat fungicide silthiofam ( 1 ) is described. Improvements to the original Discovery route allowed 300 kg of material to be prepared in two, overlapping pilot-plant campaigns. Thereafter, efforts were focused on further optimizing the pilot-plant route, and on devising alternate, lower cost routes to silthiofam. One potential new route involved a cycloaddition reaction between 3-mercapto-2-butanone and N -(2-propenyl)-3-trimethylsilylpropynamide. The cyclic product could be directly dehydrated to silthiofam, however the overall yield was modest, raw material costs were high, and there were purification problems. The route ultimately selected for development proceeds in 6 chemical steps and about 60% yield from the inexpensive precursors 3-chloro-2-butanone and methyl 3-methoxyacrylate. Key features of the route are a novel thiophene-3-carboxylate synthesis involving cycloaddition of 3-mercapto-2-butanone with the acrylate followed by acid catalyzed aromatization, the room temperature formation and silylation of a thiophene-3-carboxylate dianion, and conversion of the resulting carboxylic acid into silthiofam with negligible loss of the silyl group. The process involves isolation of just two intermediates, only one of which is purified, and uses only three organic solvents, all of which are recycled. It can be run safely on large scale to give high-purity silthiofam.",10.1021/op020206f,2002-05-10,0.7165049156884822
Organic Process Research & Development,New Practical Synthesis of the Key Intermediate of Candesartan,"The development of a new, practical synthesis of methyl 3-amino- N -[(2‘-cyanobiphenyl-4-yl)methyl]anthranilate, key intermediate of candesartan, is described, starting from methyl anthranilate. The features of our approach are as follows: ( i ) introduction of the 3-nitro group by acid catalysed rearrangement of the corresponding methyl N -nitroanthranilate; ( ii ) introduction of a (2‘-cyanobiphenyl-4-yl)methyl side chain by N -alkylation of the appropriate N -nitroanthranilic acid derivative. In the most efficient procedure methyl N,3-dinitroanthranilate was N -alkylated with 4‘-bromomethyl-biphenyl-2-nitrile. Catalytic reduction of the aromatic nitro group was accompanied with the removal of the N -nitro function to afford the required key intermediate in good yield.",10.1021/op700041z,2007-04-25,0.716497299245906
Tetrahedron,Asymmetric enamide hydrogenation in the synthesis of N-acetylcolchinol: a key intermediate for ZD6126,,10.1016/j.tetlet.2007.04.090,2007-04-23,0.716495756652899
Synthesis,New Synthetic Route to Tucatinib,"A new and improved synthetic route to tucatinib is described that involves three key intermediates. The first of these, 4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)-3-methylaniline, was prepared on a 100 g scale in 33% yield over five steps and 99% purity. Next, N 4-(4-([1,2,4]triazolo[1,5-a]pyridin-7-yloxy)-3-methylphenyl)quinazoline-4,6-diamine was isolated in 67% yield over three steps and &gt;99% purity. Then, 4,4-dimethyl-2-(methylthio)-4,5-dihydrooxazole trifluoromethanesulfonate was prepared under mild conditions in 67% yield over two steps. Finally, tucatinib was obtained in 17% yield over nine steps and in &gt;99% purity (HPLC). Purification methods used to isolate the product and the intermediates involved in the route are also reported.",10.1055/s-0037-1610706,2019-04-16,0.7162850878330576
Organic Process Research & Development,Development of an Effective Scalable Enantioselective Synthesis of the HIV-1 Entry Inhibitor BNM-III-170 as the Bis-trifluoroacetate Salt,"We report here the development and optimization of a process synthesis for the human immunodeficiency virus-1 entry inhibitor BNM-III-170 bis-trifluoroacetate salt ( 1 ). The synthesis features a dynamic-kinetic resolution to establish the initial stereogenicity. By taking advantage of significant sequence modifications of our first-generation synthesis, in conjunction with the low solubility of late-stage intermediates, the overall efficiency of the synthesis has been significantly improved, now to proceed in an overall yield of 9.64% for the 16 steps, requiring only a single chromatographic separation.",10.1021/acs.oprd.9b00353,2019-10-07,0.7162798427983205
Organic Process Research & Development,"Development of a Commercial Process for Deucravacitinib, a Deuterated API for TYK2 Inhibition","Deucravacitinib (BMS-986165) is a deuterated small-molecule TYK2 inhibitor developed for the treatment of numerous autoimmune disorders. While the first-generation discovery chemistry route to access deucravacitinib was concise and sufficient to access kilogram quantities of API, impurity control and cost-of-goods concerns necessitated the design of a new route. Once a new route was identified and demonstrated, each step was optimized for yield, purity, robustness, and sustainability. Key accomplishments include (1) the development of a novel cyclocondensation under mild conditions to afford a methylated 1,2,4-triazole with excellent regiocontrol, (2) the development of safe, homogeneous conditions to quench POCl 3 following chlorination of a substrate that is sensitive to nucleophilic and basic conditions, (3) the discovery of a robust, scalable “dual-base” palladium-catalyzed C–N coupling reaction, and (4) mechanistic understanding to inform control strategies for a number of process-related impurities in an API step amidation mediated by EDC. Ultimately, the optimized commercial route was successfully scaled up to afford more than a metric ton of deucravacitinib for clinical and commercial use.",10.1021/acs.oprd.1c00468,2022-02-17,0.7159955722726205
Organic Process Research & Development,Optimized Synthesis of a Key Intermediate of Nirmatrelvir,"In this study, the development of a concise alternative process for synthesis of a key nirmatrelvir intermediate cyclic glutamine analog is described. The process proceedes via α-cyanomethylation of dimethyl N -BocGlu in the presence of NdCl 3, followed by one-pot Raney nickel-catalyzed hydrogenation of the cyano group with concomitant cyclization and ammonolysis and subsequent deprotection of N -Boc to deliver the target intermediate cyclic glutamine analog in three steps with an 82% overall yield and 99.4 A% high-performance liquid chromatography (HPLC) purity. This study resulted in improved synthetic efficiency and stereoselectivity of α-cyanomethylation for production of a key nirmatrelvir intermediate cyclic glutamine analog.",10.1021/acs.oprd.2c00225,2022-12-20,0.7159592379235378
Journal of Organic Chemistry,Practical Synthesis of a Vanilloid Receptor-1 Antagonist,"Small molecule TRPV1 antagonists have been a recent focus in the search for pain treatment agents. We herein describe a practical and scalable synthesis of AMG 628 (1), a bis-substituted pyrimidine derivative that was identified as a highly efficacious agent, suitable for clinical development. Highlights of our approach include a practical route to a substituted benzothiazole, a scalable synthesis of an enantiopure piperazine fragment, and identification of conditions for selective coupling reactions on 2,6-dichloropyrimidine, to access the active pharmaceutical ingredient in high purity and overall yield.",10.1021/jo8002216,2008-03-20,0.7159429687994726
Journal of Organic Chemistry,"Synthesis of a Histamine H<sub>3</sub> Receptor Antagonist—Manipulation of Hydroxyproline Stereochemistry, Desymmetrization of Homopiperazine, and Nonextractive Sodium Triacetoxyborohydride Reaction Workup","We have recently completed the synthesis of 1-[2-(4-cyclobutyl-[1,4]diazepane-1-carbonyl)-4-(3-fluoro-phenoxy)-pyrrolidin-1-yl]-ethanone, a hydroxyproline-based H(3) receptor antagonist, on 100 g scale. The synthesis proceeds through four steps and route selection was driven by a desire to minimize the cost-of-goods. Naturally occurring trans-4-hydroxy-L-proline was chosen as the precursor to the target's core, which necessitated an inversion at both stereogenic centers. The inversions were accomplished through strategic employment of La Rosa's lactone and a late-stage Mitsunobu reaction. A first generation synthesis that employed N-Boc-homopiperazine was improved in a second generation approach wherein homopiperazine was directly desymmetrized. Finally, the water solubility of a key intermediate necessitated the development of a nonextractive workup for the sodium triacetoxyborohydride reduction.",10.1021/jo100629z,2010-06-10,0.7159305619663221
Organic Letters,Scalable Asymmetric Total Syntheses of (+)-Psoracorylifol B and (+)-<i>ent</i>-Psoracorylifol C,"The first, asymmetric total syntheses of potent antimicrobial Psoracorylifol B (>1.3 g obtained, dr 10.5:1) with a 9.4% overall yield on a gram scale in 14 steps and ent-Psoracorylifol C with a 4.3% yield in 16 steps were achieved. The key features of our synthesis include (i) sequential, rarely explored Achmatowicz rearrangement/bicycloketalization to construct the 6,8-dioxabicyclo[3.2.1]octane core, and (ii) Cu-mediated SN2' methylation or Johnson-Claisen rearrangement to stereoselectively install the all-carbon quaternary stereocenter. This concise, highly efficient, and scalable synthetic route may provide expedited and practical access to psoracorylifols and their analogues for further biological activity evaluation.",10.1021/ol501120m,2014-05-12,0.7158337608563825
Synlett,An Efficient Total Synthesis of (-)-Vindoline,"All articles of this category A highly efficient total synthesis of the title compound is described. Our synthesis features a highly efficient preparation of the key intermediate 11 using our novel indole synthesis methodology. A novel amine protecting protocol by means of 2,4-dinitrobenzenesulfonamides has been developed to ensure the formation of the elusive secodine-type intermediate 15 under very mild conditions. vindoline - tin-mediated indole synthesis - total synthesis - 2,4-dinitrobenzenesulfonamide - 11-hydroxytabersonine",10.1055/s-2000-6724,2000-01-01,0.7157693600112149
Tetrahedron,A simplified route to a key intermediate in the total synthesis of α-onocerin,,10.1016/s0040-4039(01)84068-5,1961-01-01,0.7156972932350164
Journal of Organic Chemistry,"Practical Asymmetric Synthesis of Aprepitant, a Potent Human NK-1 Receptor Antagonist, via a Stereoselective Lewis Acid-Catalyzed Trans Acetalization Reaction","A streamlined and high-yielding synthesis of aprepitant (1), a potent substance P (SP) receptor antagonist, is described. The enantiopure oxazinone 16 starting material was synthesized via a novel crystallization-induced dynamic resolution process. Conversion of 16 to the penultimate intermediate cis-sec-amine 9 features a highly stereoselective Lewis acid-catalyzed trans acetalization of chiral alcohol 3 with trichloroacetimidate 18 followed by inversion of the adjacent chiral center on the morpholine ring. The six-step process for the synthesis of 9 was accomplished in extremely high overall yield (81%) and with only two isolations.",10.1021/jo0203793,2002-08-28,0.7156671551867183
Organic Process Research & Development,Development and Scale-Up of an Optimized Route to the ALK Inhibitor CEP-28122,"Evolution of the process strategies to prepare CEP-28122, an anaplastic lymphoma kinase (ALK) inhibitor, is presented. The initial medicinal chemistry route, used for the preparation of key supplies for biological screening, is reviewed. In addition, the process research and development of the final optimized process for manufacture of preclinical and clinical supplies is discussed. Details regarding a blocking group strategy for selective nitration; discovery of a one-pot transfer hydrogenation to effect a reductive amination, nitro group reduction, and dehalogenation; an enzymatic resolution of a critical intermediate; and the discovery of a novel, stable, in situ generated mixed mesylate hydrochloride salt of the API are disclosed.",10.1021/op200313v,2011-12-15,0.7156536872963151
Organic Process Research & Development,Synthesis of a Nucleoside Phosphoramidate Prodrug Inhibitor of HCV NS5B Polymerase: Phenylboronate as a Transient Protecting Group,"A synthetic process for 2′- C -methylcytidine-5′-[2-[(3-hydroxy-2,2-dimethyl-1-oxopropyl)thio]ethyl- N -benzylphosphoramidate], a nucleotide prodrug inhibitor of hepatitis C virus NS5B polymerase, is described. The route developed was demonstrated on 100 g scale and featured the key application of phenylboronic acid as an effective transient means to protect the 2′,3′-hydroxyls of 2′- C -methylcytidine. This synthetic methodology resulted in a reduction in the number of isolations from five to two and an increase in the overall yield by 50% relative to the original unscalable discovery route. The synthesis and characterization of 2′- C -methylcytidine-2′,3′- O -phenylboronate is also provided.",10.1021/op500042u,2014-05-21,0.715639989056596
Journal of the American Chemical Society,Total Synthesis of (+)-Lactacystin,"A total synthesis of the novel neurotrophic agent (+)-lactacystin ( 1 ) has been achieved in 11 steps and 14% overall yield from (2 R,3 S )-3-hydroxyleucine [(+)- 16 ]. The construction and bioassay of several active analogs are also described. A new asymmetric approach furnished the four stereoisomers of 3-hydroxyleucine, as required starting materials in high overall yield and enantiomeric purity.",10.1021/ja9541544,1996-01-01,0.7156015980742013
Organic Process Research & Development,"Development of a Scalable Process for DG-041, a Potent EP<sub>3</sub> Receptor Antagonist, via Tandem Heck Reactions","DG-041 is a small molecule antagonist of the EP 3 receptor for prostaglandin E 2 that is in clinical development for treatment of peripheral artery disease (PAD). Originally produced using a six-step synthetic procedure, process optimization led to development of a four-step sequence that is readily scalable. The key step in the optimized sequence contains two sequential Heck reactions, involving an intramolecular Heck cyclization followed by an intermolecular Heck coupling, performed in one pot to produce a highly substituted indole core.",10.1021/op700107h,2007-06-20,0.7154954916243716
Organic Process Research & Development,"First Kilogram-Scale Application of the Lanthanum Catalyzed Asymmetric Amination to Synthesis of the Chiral Succinimide Derivative, A Key Intermediate for the Preparation of AS-3201","The process development of ethyl-( R )-3-amino-2,5-dioxopyrrolidine-3-carboxylate (2), the chiral intermediate for the manufacture of AS-3201 (1), is described. A practical and scalable Shibasaki asymmetric amination that generates the chiral quaternary center was developed and demonstrated on kilogram scale. A safe, convenient, and large-scale hydrogenation of the hydrazine intermediate was also developed.",10.1021/acs.oprd.6b00053,2016-05-17,0.7153973419451892
Journal of Organic Chemistry,Synthesis of the Key Intermediate of SM-406 (Xevinapant) and Its Analogues,"Efficient methods for the synthesis of three dipeptide mimetics with diazabicycloalkanone amino acid scaffolds were developed. Among them, compound 3, which contains a 1,5-diazabicyclo[6,3,0]dodecanone amino acid core structure, was used as the key intermediate of a clinical staged IAP inhibitor SM-406 (Xevinapant). Compared with the reported methods for the synthesis of compound 3 and its derivatives, our method is more efficient and more suitable for large scale preparation.",10.1021/acs.joc.2c01173,2022-09-15,0.7152543157186702
Organic Process Research & Development,"A Scalable Route to an Unusual 3,3-Dimethyl-2,3-dihydrobenzofuran Ring System Present in an HCV Drug Candidate","A scalable synthesis of a key intermediate used for the preparation of an HCV inhibitor containing an unusual dimethyldihydrobenzofuran ring is described. A key element for the successful completion of the synthesis was the correct ordering of a sequence of bromination, chlorination, and methylation to provide optimized selectivity and improved yield. A tin hydride-mediated ring closure was replaced with a more environmentally benign sulfuric acid-catalyzed Friedel–Crafts reaction. The overall yield for the preparation of the key intermediate was increased from less than 5 to 40%.",10.1021/op4003467,2014-04-02,0.715171919112076
Organic Process Research & Development,Practical Synthesis of PGI<sub>2</sub> Agonist: Resolution–Inversion–Recycle Approach of Its Chiral Intermediate,"Practical synthesis of ((2 R )-5-benzyloxy-2-hydroxy-1,2,3,4-tetrahydronaphth-2-yl)methanol ( ( R )-7b ), a key chiral intermediate for the synthesis of the novel PGI 2 agonist, ( R )-[6-[(diphenylcarbamoyloxy)methyl]-6-hydroxy-5,6,7,8-tetrahydronaphthalen-1-yloxy]acetic acid ( 1 ), was achieved via optical resolution by diastereoselective crystallization of ester derivative 18 of racemic (5-benzyloxy-2-hydroxy-1,2,3,4-tetrahydronaphth-2-yl)methanol ( 7b ) with (1 S,4 R )-(−)-camphanic acid ( (−)-CpOH ) followed by saponification. Starting from commercially available 5-hydroxy-1-tetralone ( 2 ), this process features recycling of the undesired enantiomer ( S )-7b via inversion of the C2 hydroxyl group by acid-catalyzed hydrolysis of its epoxide derivative ( S )-11 . Performing this resolution–inversion–recycle approach provided a 44% overall yield of ( R )-7b (>99% ee) from racemic 7b . The enantiopure ( R )-7b synthesized by this approach was then used to prepare 1 . This robust, reproducible, and scalable synthesis of 1 was successfully demonstrated on a pilot scale.",10.1021/op3003085,2013-02-26,0.7150294157243441
Tetrahedron,"Synthesis of 1,4,6-Trideoxy-1,4-imino-D-mannitol: a potent α-mannosidase inhibitor",,10.1016/s0040-4039(00)98217-0,1985-01-01,0.7150216402175021
Tetrahedron,Synthesis of a potent α-glucosidase inhibitor epimeric to fr 900483,,10.1016/0040-4039(91)80591-s,1991-08-01,0.7150216402175021
Tetrahedron,Synthesis of potent BCRP inhibitor—Ko143,,10.1016/j.tetlet.2007.12.130,2008-01-09,0.7150216402175021
Tetrahedron,"Formal synthesis of fumonisin B1, a potent sphingolipid biosynthesis inhibitor",,10.1016/j.tetlet.2012.04.030,2012-04-21,0.7150216402175021
Organic Process Research & Development,Process Development and Synthesis of Birinapant: Large Scale Preparation and Acid-Mediated Dimerization of the Key Indole Intermediate,"Birinapant/TL32711 ( 1 ) is a novel bivalent antagonist of the inhibitor of apoptosis (IAP) family of proteins which is currently in clinical development for the treatment of cancer and hepatitis B virus (HBV) infection. In this report, we present a detailed description of the 1 drug substance synthesis used to support our ongoing clinical studies. Key transformations in this process included the development of a scalable, high-yielding route to acyl indole 14 as well as a two-step dimerization/oxidation of indole 19 that afforded biindole 21 in excellent yield and purity (70% yield, 2 steps; >95 area% purity by HPLC analysis). In addition, partial defluorination of 21 was observed following hydrogen-mediated benzyloxycarbonyl (Cbz) protective group removal which was obviated by the use of HBr/HOAc for this transformation. The use of commercially available amino acid derivatives afforded related impurities which proved difficult to purge in subsequent steps. Thus, defining the impurity specification for these reagents was critical to providing 1 drug substance of >99 area% chemical purity. Using this process, we have successfully prepared 1 drug substance multiple times on >500-g-scale in support of our clinical development program.",10.1021/acs.oprd.5b00390,2016-01-06,0.7149682713113893
Organic Process Research & Development,Convergent Kilogram-Scale Synthesis of Dual Orexin Receptor Antagonist,"MK-6096 is an orexin receptor antagonist in clinical trials for the treatment of insomnia. Herein we describe its first kilogram-scale synthesis. Chirality on the α-methylpiperidine core was introduced in a biocatalytic transamination using a three-enzyme system with excellent enantioselectivity (>99% ee). Low diastereoselectivity of the lactam reduction was overcome by development of a camphor sulfonic acid salt formation and dr upgrade. A chemoselective O -alkylation with 5-fluoro-2-hydroxypyridine was optimized and developed. Overall, 1.2 kg of MK-6069 was prepared in nine steps and 13% overall yield.",10.1021/op3002678,2012-11-30,0.7149057222570232
Tetrahedron,"The synthesis of C3-methyl, C3-decarboxy-zaragozic acid A — A potent squalene synthase inhibitor",,10.1016/s0040-4039(00)91815-x,1993-10-01,0.7148735576804602
Organic Letters,Enantioselective Formal Total Synthesis of the Antitumor Macrolide Bryostatin 7,"A new enantioselective synthesis of Masamune's AB fragment (1) for bryostatin 7 is described. Key steps in the new route include a Meerwein-Ponndorf-Verley reduction to set the O(7) stereocenter and an alkylative union between the dithiane 6 and iodide 5 to construct the C(9)-C(10) bond. Because we have previously published a synthesis of Masamune's C-ring phenyl sulfone 2, our new route to 1 constitutes a formal total synthesis of bryostatin 7; it also corrects the previously reported spectral data for 1 in CDCl3.",10.1021/ol061626i,2006-09-01,0.7147577138424123
Journal of Organic Chemistry,A Practical Synthesis of Nitrocefin,"Nitrocefin is a key reagent for high and low throughput assays of the activities of penicillin-binding proteins (PBPs) and beta-lactamases, the former used for discovery of antibiotics and the latter for inhibitors of resistance determinants for beta-lactam antibiotics. This compound is commercially available but is prohibitively expensive because of the circuitous routes to its synthesis. We describe herein a three-step synthesis of nitrocefin that gives an overall yield of 44%. This is a practical route to the synthesis of this key reagent for drug discovery.",10.1021/jo0487395,2004-12-02,0.7146706847509103
Journal of Organic Chemistry,"C–H Arylation in the Formation of a Complex Pyrrolopyridine, the Commercial Synthesis of the Potent JAK2 Inhibitor, BMS-911543","The development of an improved short and efficient commercial synthesis of the JAK2 inhibitor, a complex pyrrolopyridine, BMS-911543, is described. During the discovery and development of this synthesis, a Pd-catalyzed C-H functionalization was invented which enabled the rapid union of the key pyrrole and imidazole fragments. The synthesis of this complex, nitrogen-rich heterocycle was accomplished in only six steps (longest linear sequence) from readily available materials.",10.1021/acs.joc.8b02383,2018-11-02,0.714657982188253
Journal of Organic Chemistry,"Practical Synthesis of a Cathepsin S Inhibitor: Route Identification, Purification Strategies, and Serendipitous Discovery of a Crystalline Salt Form","A ""redox economical"" strategy resulted in a concise, modular synthesis of compound 1, a potent Cathepsin S inhibitor. Starting from three building blocks, crude drug substance was prepared in a two-step sequence in high yield. Efficient purification of the crude drug substance was accomplished via the formation of an unusual monoethyl oxalate salt.",10.1021/jo902650b,2010-02-15,0.7145506013004366
Synthesis,New Syntheses of Isochromene,All articles of this category Isochromene is easily prepared in three steps either from the homophthalic acid (Route A) or from the 2-indanone (Route B). The synthetic Route B gives a better yield.,10.1055/s-1987-27982,1987-01-01,0.7145209773227851
Organic Process Research & Development,Investigation of Synthetic Routes to a Key Benzopyran Intermediate of a 5HT<sub>4</sub> Agonist,The supply route to GlaxoSmithKline’s 5HT 4 receptor agonist 1 centred on the construction of key benzopyran fragment 2 . Our attempts to define the final manufacturing route for this component are described through a series of disconnections. The systematic approach undertaken towards the construction of the benzopyran skeleton focused on cyclisation strategies from appropriate precursors and evaluation of the performance of the key steps.,10.1021/op900188v,2009-11-06,0.7145046911042666
Journal of the American Chemical Society,Development of an Enantioselective Synthetic Route to Neocarzinostatin Chromophore and Its Use for Multiple Radioisotopic Incorporation,"A convergent, enantioselective synthetic route to the natural product neocarzinostatin chromophore (1) is described. Synthesis of the chromophore aglycon (2) was targeted initially. Chemistry previously developed for the synthesis of a neocarzinostatin core model (4) failed in the requisite 1,3-transposition of an allylic silyl ether when applied toward the preparation of 2 with use of the more highly oxygenated substrates 27 and 54. An alternative synthetic plan was therefore developed, based upon a proposed reduction of the epoxy alcohol 58 to form the aglycon 2, a transformation that was achieved in a novel manner, using a combination of the reagents triphenylphosphine, iodine, and imidazole. The successful route to 1 and 2 began with the convergent coupling of the epoxydiyne 15, obtained in 9 steps (43% overall yield) from D-glyceraldehyde acetonide, and the cyclopentenone (+)-14, prepared in one step (75-85% yield) from the prostaglandin intermediate (+)-16, affording the alcohol 22 in 80% yield and with > or =20:1 diastereoselectivity. The alcohol 22 was then converted into the epoxy alcohol 58 in 17 steps with an average yield of 92% and an overall yield of 22%. Key features of this sequence include the diastereoselective Sharpless asymmetric epoxidation of allylic alcohol 81 (98% yield); intramolecular acetylide addition within the epoxy aldehyde 82, using Masamune's lithium diphenyltetramethyldisilazide base (85% yield); selective esterification of the diol 84 with the naphthoic acid 13 followed by selective cleavage of the chloroacetate protective group in situ to furnish the naphthoic acid ester 85 in 80% yield; and elimination of the tertiary hydroxyl group within intermediate 88 using the Martin sulfurane reagent (79% yield). Reductive transposition of the product epoxy alcohol (58) then formed neocarzinostatin chromophore aglycon (2, 71% yield). Studies directed toward the glycosylation of 2 focused initially on the preparation of the N-methylamino --> hydroxyl replacement analogue 3, an alpha-D-fucose derivative of neocarzinostatin chromophore, formed in 42% yield by a two-step Schmidt glycosylation-deprotection sequence. For the synthesis of 1, an extensive search for a suitable 2'-N-methylfucosamine glycosyl donor led to the discovery that the reaction of 2 with the trichloroacetimidate 108, containing a free N-methylamino group, formed the alpha-glycoside 114 selectively in the presence of boron trifluoride diethyl etherate. Subsequent deprotection of 114 under mildly acidic conditions then furnished the labile chromophore (1). The synthetic route was readily modified for the preparation of singly and doubly (3)H- and (14)C-labeled 1, compounds unavailable by other means, for studies of the mechanism of action of neocarzinostatin in vivo.",10.1021/ja012487x,2002-04-19,0.7144737369077282
Journal of Organic Chemistry,"An Efficient Route for the Preparation of a 21-Fluoro Progestin-16α,17α-Dioxolane, a High-Affinity Ligand for PET Imaging of the Progesterone Receptor","Two different synthetic routes were explored for the synthesis of fluoro furanyl norprogesterone (FFNP) 1, a high-affinity ligand for the progesterone receptor (PgR) that is being developed as a PET imaging agent for PgR-positive breast cancer. Both approaches proceed through a key intermediate, triol 5. The first approach, starting from keto-ketal 2, employed a dioxenyl group as a synthon for installing a corticosteroid side chain in keto-alcohol 4. The second approach, starting from propargylic acetate 12b, involved the application of a two-step method, a Pd(II)-catalyzed oxidative rearrangement followed by a base-catalyzed acetate rearrangement of the intermediate unsaturated acetate 13b, to generate the requisite corticosteroid side chain in keto-acetate 14b. This intermediate was further elaborated to the final product 1 via efficient dihydroxylation with potassium permangnate, furan acetalization with scandium triflate, and mesylation and fluorination reactions. The palladium-catalyzed route is considerably more efficient than the dioxene approach for the synthesis of key intermediate triol 5, and the scandium triflate-catalyzed acetalization, in particular, led to a considerable improvement in the overall yield of the endo furan acetal alcohol 16a. This route provides a major improvement in the overall yield of the final progestin target, FFNP 1.",10.1021/jo020190r,2002-06-14,0.7144403628701494
Tetrahedron,A new synthetic route to (±)-thienamycin via 4-exo trigonal cyclisation of carbamoyl cobalt intermediates,,10.1016/0040-4039(91)80870-c,1991-01-01,0.7144062095006064
Tetrahedron,Development of a practical and scalable route for the preparation of the deacetoxytubuvaline (dTuv) fragment of pretubulysin and analogs,,10.1016/j.tetlet.2016.01.051,2016-01-16,0.7143813913903816
Organic Letters,"Efficient Preparation of 2,4-Diaminopyrimidine Nucleosides: Total Synthesis of Lysidine and Agmatidine","An efficient route for the synthesis of 2,4-diaminopyrimidine ribosides from cytidine is described consisting of six steps with overall yields >50% and only one chromatographic step. The key amine addition step utilizes LiCl and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) to ensure clean conversion to a single tautomeric product. This route has been used to prepare the modified tRNA nucleosides lysidine and agmatidine in quantities suitable for structural characterization.",10.1021/ol301769j,2012-07-30,0.7143327126426788
Organic Letters,A Concise and Selective Synthesis of Novel 5-Aryloxyimidazole NNRTIs,"[reaction: see text] A concise and efficient route to the construction of a 5-aryloxyimidazole has been developed. The key step was the selective O-arylation of a 2,4-dimethoxybenzyl-protected imidazolone. The final compound is a potent inhibitor of HIV reverse transcriptase.",10.1021/ol060316x,2006-03-11,0.714264352730661
Journal of Organic Chemistry,"Enantioselective Formal Synthesis of (−)-Podophyllotoxin from (2<i>S</i>,3<i>R</i>)-3-Arylaziridine-2-carboxylate","Meyers' 4-aryl-1-tetralone-lactone and ent-Zhang's 2-diarylmethyl-4-oxobutanoate were synthesized in the formal synthesis of (-)-podophyllotoxin from (2S,3R)-3-arylaziridine-2-carboxylate, via 3,3-diarylpropanoate as a common intermediate, in an overall 42% yield through 10 steps and 31% yield through 6 steps, respectively. The key steps in the synthesis were regio- and diastereoselective ring opening with an aromatic nucleophile, samarium iodide promoted reductive C-N bond cleavage, and Stille coupling for introducing the vinyl functionality. The starting aziridine was enantioselectively prepared from 3,4,5-trimethoxybenzaldehyde by guanidinium ylide mediated asymmetric aziridination. All nitrogen components used in the reaction sequence are reusable as the starting guanidinium source.",10.1021/jo400147f,2013-03-15,0.7142539574651935
Organic Process Research & Development,Process Development of a Diacyl Glycerolacyltransferase-1 Inhibitor,"A synthesis of a selective diacyl glycerolacyltransferase-1 (DGAT-1) inhibitor, 1, is described. The synthesis illustrates a diketone Favorskii reaction on 9 in place of the more common ketoester variant for generation of the dicarboxycyclopentane core, the development of an efficient classical resolution of a key cyclopentyl ketoacid intermediate 4, and an ambient temperature Suzuki−Miyaura coupling which avoids epimerization of the labile aryl ketone of 1 .",10.1021/op900310v,2010-02-15,0.7141925361650305
Organic Process Research & Development,"Novel, Practical, and Scalable Approach for the Synthesis of Eldecalcitol","A novel, practical, and scalable approach for the synthesis of eldecalcitol ( 2 ), via the Horner–Wadsworth–Emmons (HWE) olefination of A-ring and C/D-ring fragments, has been described. The improved route was carried out to produce the key intermediate chiral epoxide 17 in good yield (13 steps, 9.0% overall yield) and high optical purity based on the utilization of d -mannose as a readily accessible, economically attractive chiral raw material. This process employed d -mannose as the chiral pool to directly assemble all the stereocenters of the A-ring fragment, thereby reducing the complexity of the chiral separation process, eliminating the need for asymmetric oxidation required for the construction of the C-3 stereocenter, and ultimately increasing the efficiency.",10.1021/acs.oprd.2c00369,2023-06-06,0.7141057831349796
Organic Process Research & Development,Identification and Development of an Efficient Route to SB-649915,"The discovery and development of an efficient manufacturing route to the SSRI-5-HT1A receptor antagonist 6-[(1-{2-[(2-methyl-5-quinolinyl)oxy]ethyl}-4-piperidinyl)methyl]-2 H -1,4-benzoxazin-3(4 H )-one (SB-649915) 1 is described. The existing route to 1 involved coupling quinoline 6 with piperidine 5 and was considered lengthy as a consequence of the nine synthetic steps required to prepare 5 . Two new routes to the key piperidine intermediate 5 are identified which deliver this compound in five and two steps respectively, from readily available materials using novel lithiation and Friedel–Crafts methodology respectively. The latter of these two routes was successfully demonstrated at 5 L scale to deliver 700 g of 5 . Development to the methanesulfonate 34, an alternative to quinoline 6, is also described as is the final alkylation of piperidine 5 with this methanesulfonate 34 to deliver SB-649915 1 .",10.1021/op300185s,2012-08-29,0.714018844586894
Tetrahedron,"An improved, two-step synthesis of 2,2′:6′,2″-terpyridine.",,10.1016/s0040-4039(00)78891-5,1991-04-01,0.7140124650711434
Organic Process Research & Development,"Process Research for ZG1077, a KRAS G12C Inhibitor","A novel, efficient, and robust synthetic route to ZG1077 with an atropisomer structure for KRAS G12C inhibitors was designed. The critical process parameters were optimized and established to reduce or avoid process-related impurities. The formation mechanism, purge pathways, and control strategy for these impurities are discussed. Compared with the medicinal chemistry route, the single atropisomer drug substance was obtained with chiral resolution rather than the supercritical fluid chromatogram purification technique, and it was obtained in 3.01% overall yield with >99.5% purity and 99.8% e.e. in the novel route. However, the overall yield is only 0.56%, and the purity and chiral purity were less than 99.0% in the medicinal chemistry route. The process is suitable to obtain enough active pharmaceutical ingredients for preclinical and clinical studies.",10.1021/acs.oprd.2c00284,2022-10-09,0.7139856643789403
Journal of the American Chemical Society,Total Synthesis of (±)-Actinophyllic Acid,The first total synthesis of (+/-)-actinophyllic acid (1) is reported. Key steps of this synthesis include an intramolecular oxidative coupling of ketone and malonic ester enolates and an aza-Cope-Mannich rearrangement that assembled the core structure of the natural product's unique ring system. The synthesis was accomplished from di-tert-butyl malonate in 8% overall yield by a concise sequence that proceeds by way of only seven isolated intermediates.,10.1021/ja803158y,2008-05-21,0.7138837941934039
Organic Process Research & Development,An Efficient Large-Scale Synthesis of a Naphthylacetic Acid CRTH2 Receptor Antagonist,"An efficient and practical synthesis of a naphthylacetic acid CRTH2 receptor antagonist is reported. Michael addition of ethyl t -butyl malonate to an allenoate afforded a triester, which was selectively hydrolyzed and decarboxylated to give a benzylidenepentanedioic acid monoester. Treatment of this compound with potassium acetate and acetic anhydride produced the naphthylacetate core. The triflate of the key building block was coupled with a zinc reagent of the side chain under improved Negishi coupling conditions to afford the target product. The process was successfully scaled up to produce over 2 kg of the API.",10.1021/op300306c,2013-03-18,0.7138545058836923
Tetrahedron,A synthetic route to the hexahydrobenzofuran nucleus of avermectins via diazoketone cyclization,,10.1016/s0040-4039(00)96876-x,1987-01-01,0.713841010217709
Tetrahedron,"Studies toward the synthesis of cinachyramine. An efficient route to 1,5-diazabicyclo[4.4.0]dec-5-enes",,10.1016/j.tetlet.2014.12.071,2014-12-22,0.7138143407492589
Organic Process Research & Development,A Scaleable Route to the Pure Enantiomers of Verapamil,"A versatile route to single enantiomer verapamil from readily available raw materials is described. The key intermediate, 4-cyano-4-(3,4-dimethoxyphenyl)-5-methyl hexanoic acid (verapamilic acid), was resolved efficiently with α-methyl benzylamine. Stereochemical integrity at the quarternary carbon centre was preserved through subsequent steps to give either ( R )-or ( S )-verapamil in good overall yield. This sequence incorporated a selective borane-mediated reduction of a tertiary amide. Process scale-up to the pilot plant has been demonstrated successfully for the resolution step.",10.1021/op000059q,2000-08-19,0.7137414404503989
Organic Process Research & Development,Development of a Practical Synthesis of Stearoyl-CoA Desaturase (SCD1) Inhibitor MK-8245,A practical kilogram scale chromatography-free synthesis of stearoyl-CoA desaturase 1 (SCD1) inhibitor MK-8245 is described. The key features of this sequence include an efficient addition–elimination reaction of a piperidine fragment with a 3-bromoisoxaline followed by an iodine-mediated oxidation to the corresponding isoxazole. The development of a safe and scalable tetrazole formation protocol is also presented.,10.1021/op200186d,2011-08-23,0.7137198956615848
Organic Letters,Efficient Total Synthesis of Ammosamide B,"A total synthesis of ammosamide B, a metabolite of the marine-derived Streptomyces strain CNR-698, has been executed in nine steps and 6.9% overall yield. The key step involves the condensation of a 4,6-diBoc-protected 1,3,4,6-tetraaminobenzene derivative with dimethyl 2-ketoglutaconate, which effectively constructs the pyrrolidinone ring and the quinoline ring in a single step. This contributes a unique approach to the synthesis of pyrroloquinoline alkaloids that offers the advantages of brevity and relatively high overall yield.",10.1021/ol101215x,2010-06-01,0.713696624029256
European Journal of Organic Chemistry,A Concise Asymmetric Synthesis of (–)‐Hongconin and (–)‐1‐<i>epi</i>‐Hongconin,Abstract A concise asymmetric synthesis of (–)‐hongconin and (–)‐1‐ epi ‐hongconin is described. The synthesis features an efficient combination of Dötz benzannulation or lactaldehyde arylation and the oxa‐Pictet–Spengler reaction as the key steps. The synthesis is completed in 10–11 steps from the chiral pool material ( R )‐methyl lactate.,10.1002/ejoc.201000560,2010-06-09,0.7135781474116627
Tetrahedron,An improved synthesis of a selective αvβ3-integrin antagonist cyclo(-RGDfK-),,10.1016/s0040-4039(00)01060-1,2000-08-01,0.7135687050681573
Journal of the American Chemical Society,Total Synthesis of (±)-Bisabosqual A,"The synthesis of the novel squalene synthase inhibitor, bisabosqual A, was completed in 14 steps (longest linear sequence) from commercially available starting materials. The doubly convergent route employs a tandem 5-exo, 6-exo radical cyclization as the key step. This reaction assembles the fully functionalized tetracyclic core and introduces three stereogenic centers. Other effective transformations are the regioselective deoxygenation of an advanced enone intermediate and the chemo- and diastereoselective addition of trimethylaluminum to a ketone in the presence of esters.",10.1021/ja3108577,2012-12-27,0.7135263874252465
Organic Letters,Toward the Total Synthesis of Phorboxazole B:  An Efficient Synthesis of the C20−C46 Segment,"An efficient synthesis of the C20-C46 segment of phorboxazole B is described. The key steps involved Hg(OAc)(2)/I(2)-induced cyclization to construct the cis-tetrahydropyran moiety, the coupling of the metalated 2-methyloxazole 7 with lactone 6, and Julia olefination to furnish the conjugated diene moiety.",10.1021/ol048275x,2004-10-15,0.7134558766518646
Journal of Organic Chemistry,"Practical Asymmetric Synthesis of 1,2-Diamines in the 3-Aminoazepane Series",A simple and versatile method for the enantio- and diastereoselective synthesis of mono- or disubstituted 3-aminoazepanes is described. The key step involves a highly regio- and diastereoselective tandem ring-enlargement/alkylation or reduction process. This novel synthetic route provides enantiomerically pure constrained diamines interesting as scaffolds for medicinal chemistry.,10.1021/jo026711s,2003-02-20,0.7134088447162044
Organic Process Research & Development,"An Improved Synthesis of the Selective Matrix Metalloproteinase Inhibitor, Ro 28-2653","An efficient synthesis of Ro 28-2653, a selective matrix metalloproteinase inhibitor, has been developed. The title compound was prepared in four steps and 76% overall yield from 4-biphenylacetic acid. The key, barbituric acid formation step was significantly improved by using 2-propanol and potassium tert -butoxide as the solvent and base, respectively, instead of the typical ethanol and sodium ethoxide combination.",10.1021/op049965j,2004-04-03,0.7133502667118106
Organic Letters,"Enantioselective Total Synthesis of (+)-Largazole, a Potent Inhibitor of Histone Deacetylase","An enantioselective total synthesis of the cytotoxic natural product (+)-largazole (1) is described. It is a potent histone deacetylase inhibitor. Our synthesis is convergent and involves the assembly of thiazole 3-derived carboxylic acid with amino ester 4 followed by cycloamidation of the corresponding amino acid. The synthesis features an efficient cross-metathesis, an enzymatic kinetic resolution of a beta-hydroxy ester, a selective removal of a Boc-protecting group, a HATU/HOAt-promoted cycloamidation reaction, and synthetic manipulations to a sensitive thioester functional group.",10.1021/ol8014623,2008-07-29,0.7132644444407928
Journal of Organic Chemistry,Macrocyclic Bisindolylmaleimides:  Synthesis by Inter- and Intramolecular Alkylation,"Macrocyclic bisindolylmaleimides 1 − 4 have been identified as competitive reversible inhibitors of PKC β 1 and β 2 and are being advanced to the clinic for evaluation as a treatment of retinopathy associated with diabetic complications. Highly convergent and stereoselective syntheses of 1 − 4 have been developed. The key synthetic step involves intermolecular alkylation of symmetrical bisindolylmaleimide 9 with chiral bisalkylating agent 8c and is amenable to the preparation of multikilogram quantities of these compounds. The synthetic sequence to 1, the most active compound, proceeds in 11 steps and 26% overall yield (>98% ee) from ( R )-1-chloro-2,3-propanediol. No chromatographic purifications are required throughout the process and the final product is isolated in >97% purity after crystallization from DMF/MeOH. Synthesis of 1 − 4 by intramolecular alkylation proved less efficient, requiring 17 steps and affording 1 − 4 in lower overall yields of 6.0−8.5%.",10.1021/jo971980h,1998-02-28,0.7131495563611412
Tetrahedron,An efficient and scalable synthesis of N-(benzyloxycarbonyl)- and N-(methyloxycarbonyl)-(S)-vinylglycinol,,10.1016/j.tetlet.2010.04.059,2010-04-19,0.7131397916371883
Organic Process Research & Development,A New and Improved Process for <i>N</i>-(4-Chloro-3-cyano-7-ethoxyquinolin-6-yl)acetamide,"A new and improved synthetic route to N -(4-chloro-3-cyano-7-ethoxyquinolin-6-yl)acetamide ( 1 ) is described on a kilogram scale. The key step is the basic cyclization of o -[(2-cyanovinyl)amino]benzoate ( 14 ) in t BuONa/ t BuOH system to give the 3-cyano-4-hydroxyquinoline ( 7 ). The final product 1 is obtained with 49% overall yield (seven steps) and 98.9% purity (HPLC), which makes it a cost-effective and commercially friendly process for scale-up operations.",10.1021/op300260m,2012-11-08,0.7130494089793912
Organic Process Research & Development,Discovery and Development of a Commercial Synthesis of Azafenidin,"A commercial synthesis of the DuPont herbicide azafenidin is described. Discovery of a novel synthesis of the triazolinone ring system and a practical, environmentally benign process to 5-cyanovaleramide were critical breakthroughs in enabling azafenidin to be manufactured at an acceptable cost. The process began with the selective hydrolysis of DuPont's nylon intermediate, adiponitrile, to 5-cyanovaleramide. This was converted via Hofmann rearrangement and Pinner-type cyclization to afford the key amidine carboxylate intermediate containing both carbon atoms of the triazolinone ring. The preservation of all six carbon atoms of adiponitrile set up a 2 + 3 cyclocondensation with arylhydrazines, which replaced a costly 4 + 1 cyclocondensation of an amidrazone with phosgene or a phosgene surrogate used in the original route. This new triazolinone process was optimized to afford the commercial product in a highly efficient and economical fashion.",10.1021/op9901994,2001-10-23,0.7130484076493816
Organic Process Research & Development,Development of a Practical Synthesis of DPP IV Inhibitor LY2497282,"A new synthetic route to LY2497282 ( 1 ), a potent and selective DPP IV inhibitor for the potential treatment of diabetes, suitable for the preparation of multikilogram quantities is described. The key step involved a stereoselective addition of the dianion of nicotinamide 8 to N -dibenzyl-protected α-amino aldehyde 12, which was derived from N -acetyl-protected amino ester 14 without epimerization. The desired Felkin-Anh nonchelation controlled anti -amino alcohol 11 was isolated with >99% HPLC area and >99% ee by crystallization. After removing the dibenzyl protecting group under transfer hydrogenation conditions, LY2497282 ( 1 ) was finally obtained in 39% overall yield with a six-step longest linear sequence starting from N -acetyl-protected amino ester 14 .",10.1021/op700235c,2008-03-01,0.7130131435096458
Organic Process Research & Development,"Process Development for a Large Scale Stereoselective Synthesis of (<i>Z</i>)-(1-Bromobut-1-ene-1,2-diyl)dibenzene, a Key Intermediate of a Selective Estrogen Receptor Modulator","Two efficient large scale syntheses of ( Z )-(1-bromobut-1-ene-1,2-diyl)dibenzene are described. The first is a three-step synthetic sequence from trimethyl(phenylethynyl)silane in 63% overall yield. The key transformations involved the stereospecific carbometalation reaction of trimethyl(phenylethynyl)silane followed by a bromination. Subsequent Miyaura−Suzuki coupling with phenylboronic acid and transformation of the vinyltrimethylsilane to a vinyl bromide afforded the target. In an improved synthesis, a stereoselective nickel acetylacetonate catalyzed PhZnEt addition to but-1-ynylbenzene, generated an organozincate intermediate, which was brominated in 58−62% overall yield. A key feature of this work was the production of highly regiopure olefin. The optimization effort that resulted in the utilization of substoichiometric amounts of Ph 2 Zn and the safety precautions taken to facilitate process scale-up are discussed.",10.1021/op100112r,2010-09-02,0.7129310288558001
Journal of Organic Chemistry,Semisynthesis of an Antifungal Lipopeptide Echinocandin,"Compound 1 is a macrocyclic lipopeptide belonging to the echinocandin family, which has been effective in treating systemic fungal infections. In this paper, we report a unique regio-, chemo-, and stereoselective synthesis of 1 in four steps from the deacylated nucleus 3 in an impressive 83% overall yield. Highlights of this synthesis include a selective reduction of the amide to the amine and a highly stereoselective (99:1 α/β) introduction of the 2-aminoethyl hemiaminal. In addition, the synthesis of the naphthoyl side chain was accomplished in three steps in 79% overall isolated yield from commercially available 6-bromo-2-naphthol.",10.1021/jo9822232,1999-03-11,0.7127826725802111
Tetrahedron,"Ethyl oxaorotate - a new synthetic route to 1,3-oxazime-2,6-diones",,10.1016/s0040-4039(00)93698-0,1976-01-01,0.712732396912789
Journal of Organic Chemistry,A Practical Synthesis of<i>m</i>-Prostaglandin E Synthase-1 Inhibitor MK-7285,"A practical, kilogram-scale chromatography-free synthesis of mPGE synthase I inhibitor MK-7285 is described. The route features a convergent assembly of the core phenanthrene unit via amide-directed ortho-metalation and proximity-induced anionic cyclization, followed by imidazole synthesis and late-stage cyanation.",10.1021/jo901798d,2009-09-24,0.7126529769848388
Organic Process Research & Development,Large-Scale Synthesis of LPA1-Receptor Antagonist ACT-1016-0707,"The development and execution of the large-scale synthesis of LPA1-antagonist ACT-1016-0707 is described. Key developments were an improved nitrile hydrolysis, a high-yielding, safe, and easy-to-perform amide coupling, and the isolation and purification of several, previously oily intermediates as crystalline solids. The yield of the longest linear synthesis sequence of nine steps was 34% on a 450 g scale with respect to the final product.",10.1021/acs.oprd.3c00423,2024-02-06,0.7124978422307964
Organic Letters,"Asymmetric Synthesis of (−)-1-Hydroxyquinolizidinone, a Common Intermediate for the Syntheses of (−)-Homopumiliotoxin 223G and (−)-Epiquinamide",The short and efficient asymmetric synthesis of (-)-1-hydroxyquinolizidinone was achieved in seven steps and 25.2% overall yield from readily available 5-chloropentanal. It is a key intermediate in the formal syntheses of (-)-homopumilotoxin 223G and (-)-epiquinamide.,10.1021/ol701952y,2007-10-12,0.7124234179879841
Journal of Organic Chemistry,Synthesis of a CGRP Receptor Antagonist via an Asymmetric Synthesis of 3-Fluoro-4-aminopiperidine,"A practical and efficient enantioselective synthesis of the calcitonin gene-related peptide receptor antagonist 1 has been developed. The key structural component of the active pharmaceutical ingredient is a syn-1,2-amino-fluoropiperidine 4. Two approaches were developed to synthesize this important pharmacophore. Initially, Ru-catalyzed asymmetric hydrogenation of fluoride-substituted enamide 8 enabled the synthesis of sufficient quantities of compound 1 to support early preclinical studies. Subsequently, a novel, cost-effective route to this intermediate was developed utilizing a dynamic kinetic asymmetric transamination of ketone 9. This synthesis also features a robust Ullmann coupling to install a bis-aryl ether using a soluble Cu(I) catalyst. Finally, an enzymatic desymmetrization of meso-diester 7 was exploited for the construction of the γ-lactam moiety in 1.",10.1021/acs.joc.9b00569,2019-05-24,0.7124198983179612
Journal of Organic Chemistry,Diastereoselective Synthesis of Allosecurinine and Viroallosecurinine from Menisdaurilide,"A new and versatile synthetic route to Securinega alkaloids is reported. The first synthesis of allosecurinine has been accomplished in seven steps and 40% yield, starting from (+)-menisdaurilide, using a vinylogous Mannich reaction as the key transformation. Similarly, viroallosecurinine has been synthesized from (-)-menisdaurilide.",10.1021/jo801470u,2008-09-10,0.7124016469552724
Organic Letters,Biomimetic Enantioselective Total Synthesis of (−)-Petromindole,"The first enantioselective total synthesis of (-)-petromindole, an architecturally distinct congener of indole diterpene family, has been achieved. Key features of this synthetic route include the scalable and concise synthesis of tricyclic allylic alcohol from enantiopure Wieland-Mischer ketone derivative, and TMSOTf-mediated, highly efficient biomimetic C-4 cyclization of indole derivative for the rapid construction of a hexacyclic skeleton of petromindole.",10.1021/acs.orglett.7b03768,2018-01-16,0.7123971864215282
Synthesis,Synthesis of (-)-Actinonin,Synthesis of (-)-actinonin in 17% overall yield was accomplished in seven steps via the formation of an isoimide derivative as the key intermediate. The synthesis was carried out using commercially available dimethyl maleate without the use of a highly expensive reagent.,10.1055/s-0030-1260461,2011-05-05,0.7123644661211095
Organic Process Research & Development,Process Development of the PDE4 Inhibitor K-34,"A short and practical synthesis of the PDE4 inhibitor K-34 ( 1 ) was developed. This synthesis was achieved in four steps and with a 58% overall yield. The unique spiro acetal was created with exceptionally high yield by utilizing the neighbor carboxylic acid assistance. This synthesis also features efficient ketone construction with 4-pyridinylmethyl anion 9 and ester 18, in which overreaction should be prohibited by quick in situ enolate formation. The overall synthesis was carried out under mild conditions and used a simple procedure suitable for large-scale production.",10.1021/op100291g,2011-01-04,0.7123484522764337
Organic Process Research & Development,"Process Development of 4-[<i>N</i>-Methyl-<i>N</i>-(tetrahydropyran-4-yl)aminomethyl]aniline Dihydrochloride:  A Key Intermediate for TAK-779, a Small-Molecule Nonpeptide CCR5 Antagonist","A new and efficient synthesis of 4-[ N -methyl- N -(tetrahydropyran-4-yl)aminomethyl]aniline dihydrochloride, a key intermediate for the CCR5 antagonist TAK-779, is described. Reductive alkylation of methylamine with tetrahydro-4 H -pyran-4-one followed by alkylation of N -methyl- N -(tetrahydropyran-4-yl)amine with 4-nitrobenzylbromide and reduction of N -(4-nitrobenzyl)- N -(tetrahydropyran-4-yl)amine results in a 78% isolated yield from the starting materials by a scalable method, using only commercially available reagents.",10.1021/op010052o,2001-11-30,0.7123068507725092
Synthesis,A Short and Improved Synthesis of the Antiprotozoal Abietane Diterpenoid (–)-Sugikurojin A,"An efficient and straightforward semisynthesis of the antiprotozoal abietane diterpenoid (–)-sugikurojin A, starting from the readily available methyl ester of callitrisic acid (4- epi -dehydroabietic acid­) isolated from sandarac resin, is reported. This optimized semi­synthetic route provides a convenient source of the antiprotozoal compound, in four steps from methyl callitrisate in 50% overall yield, for further biological studies.",10.1055/s-0036-1588353,2016-11-28,0.7122997467802543
Organic Process Research & Development,Practical and Scalable Manufacturing Process for Plasma Kallikrein Inhibitor ASP5069,"The plasma kallikrein inhibitor ASP5069 is a promising drug candidate for the treatment of edema and hematoma and for the prevention of bleeding during surgery. Here, we report the development of a practical and scalable process for manufacturing ASP5069 that features a convergent synthetic approach, suppression of impurity formation, effective purification of the amine compound by extraction, improved reproducibility of the reductive amination reaction, and a drying process for the dihydrate form. This process was successfully used to prepare >100 g of ASP5069.",10.1021/acs.oprd.0c00291,2020-11-16,0.7122831123729934
Tetrahedron,Novel synthetic route to the tricyclic core of (±)-galanthamine,,10.1016/j.tetlet.2009.06.055,2009-06-15,0.7122379191168711
Organic Process Research & Development,Synthesis of Nirmatrelvir: Design and Optimization of an Efficient Telescoped Amidation–Dehydration Sequence,"Development of a scalable route for the synthesis of nirmatrelvir, the novel SARS-CoV-2 3C-like protease inhibitor discovered in 2020 by Pfizer scientists, was initiated shortly thereafter to supply material for the first clinical studies. This route was optimized for commercial manufacture of nirmatrelvir in high yield and acceptable quality with consideration of efficiency and sustainability. Herein, we report the evolution of final steps (3–5) used to synthesize nirmatrelvir (steps 3–5), from the manufacture of the initial regulatory lot to the design and implementation of the final commercial process.",10.1021/acs.oprd.3c00250,2023-11-17,0.7121161694319879
Journal of the American Chemical Society,"Total Synthesis of the Tricyclic Marine Alkaloids (−)-Lepadiformine, (+)-Cylindricine C, and (−)-Fasicularin via a Common Intermediate Formed by Formic Acid-Induced Intramolecular Conjugate Azaspirocyclization","A very short and efficient enantioselective total synthesis of the tricyclic marine alkaloids (-)-lepadiformine (3), (+)-cylindricine C (1c), and (-)-fasicularin (4) has been developed utilizing the formyloxy 1-azaspiro[4.5]decane 5 as a common intermediate. The key strategic element for the synthesis was the formic acid-induced intramolecular conjugate azaspirocyclization, which proved to be a highly efficient and stereoselective way to rapid construction of the 1-azaspirocyclic substructure of these natural products in a single operation. Thus, the common intermediate 5, synthesized in two steps with 70% overall yield starting from the known (S)-N-Boc-2-pyrrolidinone 7 via the conjugate spirocyclization using an acyclic ketoamide 6, was utilized for the concise and stereoselective total synthesis of (-)-lepadiformine (3), which was accomplished in seven steps with 45% overall yield from 5 (31% yield from 7). The developed strategy based on the conjugate spirocyclization was also applied to the stereoselective total synthesis of (+)-cylindricine C (1c), which was achieved in 10 steps from 5 in 18% overall yield (12% yield from 7). Further application of this approach using 5 led to the synthesis of (-)-fasicularin (4), wherein an extremely efficient method for the introduction of the thiocyanato group via an aziridinium intermediate at the last step was developed. Thus, the highly efficient first enantioselective total synthesis of (-)-fasicularin was accomplished in nine steps with an overall yield of 41% from 5 (28% yield from 7).",10.1021/ja040213e,2005-01-11,0.7119741793137052
Synthesis,An Efficient and Practical Total Synthesis of (±)-α-Cuparenone,A one-pot cyclopentannulation approach as the key step for the total synthesis of (±)-α-cuparenone is described.,10.1055/s-2007-990899,2007-12-01,0.7119727614968698
Organic Process Research & Development,"Process Research and Scale-up of a Commercialisable Route to Maraviroc (UK-427,857), a CCR-5 Receptor Antagonist","A six-step synthetic route to the CCR-5 receptor antagonist, Maraviroc (UK-427,857) ( 1 ) has been developed and demonstrated at scale in a pilot plant. The route has supported four Pilot-Plant campaigns and has produced multikilogram quantities of 1 . Continued development of the synthetic route has resulted in a robust process with improved throughput compared to that of the original synthesis (Haycock-Lewandowski, S. J.; Mawby, N. J.; Wilder, A.; Ahman, J. Org. Process Res. Dev. 2008, 12, 1094−1103).",10.1021/op800062d,2008-10-04,0.7119307193099097
Synthesis,"A Practical Synthesis of (S)-tert-Butyl 3-Methyl-1,4-diazepane-1-carboxylate, the Key Intermediate of Rho–Kinase Inhibitor K-115","A practical synthesis of ( S )- tert -butyl 3-methyl-1,4-di­azepane-1-carboxylate has been established for supplying this key intermediate of Rho–kinase inhibitor K-115 in a multikilogram production. The chiral 1,4-diazepane was constructed by intramolecular Fukuyama–Mitsunobu cyclization of a N -nosyl diamino alcohol starting from the commercially available ( S )- or ( R )-2-aminopropan-1-ol. In the same manner, an enantiomeric pair of a structural isomer were prepared for demonstration of the synthetic utility.",10.1055/s-0032-1316771,2012-08-31,0.7119177931907199
Journal of Organic Chemistry,A Practical Synthesis for the Core Structure of a Family of Selective Prostaglandin D<sub>2</sub> Receptor Antagonists,"A convergent synthesis was developed for the production of the core structure of prostaglandin D(2) receptor antagonists for the treatment of allergic rhinitis. The key steps in this synthesis were a highly diastereoselective alkylation of (+)-nopinone, a chemo- and stereoselective reduction of an oxime to an amine, and a well-controlled reduction of an aminoalkyne to a (Z)-olefin.",10.1021/jo026511g,2003-02-19,0.7119109490693681
Organic Letters,Total Synthesis of Brevisamide,"The second total synthesis of Brevisamide, a marine cyclic ether alkaloid from Karenia brevis, is reported. This streamlined synthesis proceeds in 21 steps, 14 steps longest linear sequence, in 5.2% overall yield and features a key SmI(2) reductive cyclization step to access the tetrasubstituted pyran core.",10.1021/ol9015755,2009-07-29,0.7118811864845375
Organic Process Research & Development,"A New Efficient Synthetic Process for an Endothelin Receptor Antagonist, Bosentan Monohydrate","A new and efficient synthetic process for the synthesis of an endothelin receptor antagonist, bosentan monohydrate, involves the coupling of p - tert -butyl- N -(6-chloro-5-(2-methoxy phenoxy)-2,2′-bipyrimidin-4-yl)benzenesulfonamide ( 7 ) with (2,2-dimethyl-1,3-dioxolane-4,5-diyl)dimethanol ( 14 ) as a key step. This new process provides desired bosentan monohydrate ( 1 ) with better quality and yields. Our new methodology consists of technical innovations/improvements which totally eliminate the probability for the formation of critical impurities such as pyrimidinone 8, dimer impurity 9, and N-alkylated impurity 13 in the final drug substance.",10.1021/op400100s,2013-07-15,0.7118435637972614
Synlett,Gram-Scale Synthesis of (±)-Tylophorine,"Abstract We report a practical scalable synthesis of the natural product (±)-tylophorine by using an operationally simple protecting-group-free route from readily accessible starting materials. Synthesis of a cyclic N-acetyl diester compound through cyclization, followed by two key steps (decarboxylation and a Clemmensen reduction), provides access to the target molecule.",10.1055/a-2351-4828,2024-06-24,0.7118007397271967
Synthesis,"An Alternative Synthetic Route to (3R,5S,1′S)-5-{1′-[(tert-Butyloxycarbonyl)amino]-3′-methylbutyl}-3-methyldihydrofuran-2(3H)-one, a Precursor of a Leu-Ala Hydroxyethylene Isostere","An improved synthetic route to (3 R ,5 S ,1′ S )-5-{1′-[( tert -butyl­oxycarbonyl)amino]-3′-methylbutyl}-3-methyldihydrofuran-2(3 H )-one, a lactone precursor of the Leu-Ala (2 R ,4 S ,5 S ) hydroxyethylene isostere found in many peptidomimetic aspartyl protease inhibitors of Alzheimer’s­ disease, is devised. Alkylation of N -Boc-leucinal with the lithium salt of benzyl propargyl ether instead of ethyl propiolate is the key toward a more reproducible and efficient route to obtain the title lactone from N -Boc- l -leucine in six steps, and an overall yield of 16%.",10.1055/s-0034-1381036,2015-07-21,0.711778680654577
Organic Process Research & Development,"Early Process Development of an LPAR1 Antagonist, GS-2278","( R )-1-(2,5-Difluoropyridin-3-yl)ethyl(1-methyl-4-(5-(2-(trifluoromethyl)pyrimidine-5-carboxamido)pyridin-2-yl)-1 H -1,2,3-triazol-5-yl)carbamate (GS-2278) is a lysophosphatidic acid receptor 1 antagonist under development for the treatment of idiopathic pulmonary fibrosis. GS-2278 is assembled in a 9-step sequence. Initially, 2-bromo-5-fluoropyridine is metalated and trapped with ethyl difluoroacetate. Then, after condensation with tosyl hydrazide, Sakai cyclization with methylamine, and carboxylation with carbon dioxide, the triazole carboxylic acid core is generated. For the final assembly, the core is elaborated through a two-step hydroxamic acid formation and Lossen rearrangement to form an isocyanate which is trapped in situ by a chiral alcohol. The resulting carbamate is Boc-deprotected and subjected to amide coupling with a pyrimidine carboxylic acid to yield the active pharmaceutical ingredient. Process development was conducted to determine reaction and isolation conditions to enable scale-ups to support preclinical and early clinical studies. This paper focuses on the development of conditions from the medicinal chemistry route to the Ph 1 manufacturing route.",10.1021/acs.oprd.4c00369,2024-11-05,0.7117756235484954
Journal of Organic Chemistry,A Concise Synthesis of a Novel Antiangiogenic Tyrosine Kinase Inhibitor,An efficient synthesis of the potent KDR inhibitor 3-[5-[[4-(methylsulfonyl)-1-piperazinyl]methyl]-1H-indole-2-yl]quinolin-2(1H)-one (1) is described. The process features a noncryogenic indole boronation and a dicyclohexylamine-mediated Suzuki coupling.,10.1021/jo048334k,2004-11-23,0.711770103158032
Journal of the American Chemical Society,Enantioselective Synthesis of (−)-Codeine and (−)-Morphine,"A new synthetic strategy for the synthesis of the opiate and amaryllidaceae alkaloids emerges employing a Pd-catalyzed asymmetric allylic alkylation to set the stereochemistry. The pivotal tricyclic intermediate is available in six steps from 2-bromovanillin and the monoester of methyl 6-hydroxycyclohexene-1-carboxylate, the latter available from glutaraldehyde and the Emmons-Wadsworth-Horner phosphate reagent. This intermediate requires only two steps to convert to (-)-galanthamine. Using a Heck vinylation, we found that the fourth ring of codeine/morphine is formed. The final ring formation involves a novel visible light-promoted hydroamination. Thus, six steps are required to convert the pivotal tricyclic intermediate into codeine, which has been demethylated in high yield to morphine.",10.1021/ja0283394,2002-11-15,0.7117591056964092
Tetrahedron,An efficient two-step synthesis of 3-allylindoles,,10.1016/j.tetlet.2005.11.134,2005-12-16,0.7116772097115658
Synthesis,An Efficient One-Step Synthesis of 3-Oxoalkanenitriles,,10.1055/s-1983-30316,1983-01-01,0.7116772097115658
Tetrahedron,Total synthesis of leustroducsin B via a convergent route,,10.1016/j.tetlet.2007.03.152,2007-04-03,0.711660085642246
Organic Process Research & Development,Practical and Scalable Two-Step Process for 6-(2-Fluoro-4-nitrophenyl)-2-oxa-6-azaspiro[3.3]heptane: A Key Intermediate of the Potent Antibiotic Drug Candidate TBI-223,"High Resolution Image Download MS PowerPoint Slide A low-cost, protecting group-free route to 6-(2-fluoro-4-nitrophenyl)-2-oxa-6-azaspiro[3.3]heptane ( 1 ), the starting material for the in-development tuberculosis treatment TBI-223, is described. The key bond forming step in this route is the creation of the azetidine ring through a hydroxide-facilitated alkylation of 2-fluoro-4-nitroaniline ( 2 ) with 3,3-bis(bromomethyl)oxetane (BBMO, 3 ). After optimization, this ring formation reaction was demonstrated at 100 g scale with isolated yield of 87% and final product purity of >99%. The alkylating agent 3 was synthesized using an optimized procedure that starts from tribromoneopentyl alcohol (TBNPA, 4 ), a commercially available flame retardant. Treatment of 4 with sodium hydroxide under Schotten–Baumann conditions closed the oxetane ring, and after distillation, 3 was recovered in 72% yield and >95% purity. This new approach to compound 1 avoids the previous drawbacks associated with the synthesis of 2-oxa-6-azaspiro[3,3]heptane ( 5 ), the major cost driver used in previous routes to TBI-223. The optimization and multigram scale-up results for this new route are reported herein.",10.1021/acs.oprd.3c00148,2023-07-12,0.711482356392124
Organic Process Research & Development,"A Scalable Synthesis of CE-157119 HCl Salt, an SRI/5-HT<sub>2A</sub> Antagonist","A scalable synthesis of CE-157119 HCl salt ( 1 ), an SRI/5-HT 2A antagonist, was developed via the regioselective S N Ar etherification between a phenol and an N -methylamide. This early development route shortened the original 5-step synthesis to three steps, eliminated all chromatography and increased the overall yield from 15% to 34%. The process was implemented for API manufacture from 100-g scale to multikilogram scale.",10.1021/op3002273,2012-10-14,0.7113702304654312
Tetrahedron,Convergent synthesis of potent COX-2 inhibitor inotilone,,10.1016/j.tetlet.2007.03.166,2007-04-05,0.7113665352228293
Organic Letters,"Stereoselective Synthesis of the Glycosidase Inhibitor Australine through a One-Pot, Double-Cyclization Strategy","[reaction: see text] A stereocontrolled, convergent synthesis of the alkaloid australine, a glycosidase inhibitor of the pyrrolizidine class, is described. The chiral starting materials were ketone 3, derived from L-erythrulose, and alpha-alkoxy aldehyde 4, prepared from L-malic acid. A key step of the synthesis was the highly stereoselective aldol reaction between 4 and a Z boron enolate derived from 3. Another key step was the one-pot construction of the bicyclic pyrrolizidine system by means of a three-step sequence of SN2 displacements induced by benzylamine on a trimesylate precursor.",10.1021/ol062570v,2006-12-06,0.7113636050378037
Organic Process Research & Development,"A New Scalable Route to 4-(2-Hydroxyethyl)-1,3-dihydro-2<i>H</i>-indol-2-one: A Key Intermediate for Ropinirole Hydrochloride","A new and efficient manufacturing technology is disclosed in the present work for the preparation of 4-(2-hydroxyethyl)-1,3-dihydro-2 H -indol-2-one, which is a key intermediate for ropinirole hydrochloride. The whole process gives the target molecule in 71% overall yield with 99% purity. In the final step, a novel nitro reduction/ring-closing/debenzylation takes place in one pot. All the intermediates can be used directly for the next step without purification in this process.",10.1021/op400024a,2013-03-21,0.711338998255197
Organic Process Research & Development,"Scalable, Economical, and Practical Synthesis of 4-(Difluoromethyl)pyridin-2-amine, a Key Intermediate for Lipid Kinase Inhibitors","High Resolution Image Download MS PowerPoint Slide A new, scalable, rapid, high yielding, and practical synthesis of 4-(difluoromethyl)pyridin-2-amine provides a key intermediate for the preparation of numerous protein kinase inhibitors and clinical candidates targeting phosphoinositide 3-kinase (PI3K) and the mechanistic target of rapamycin (mTOR) kinase. Starting from 2,2-difluoroacetic anhydride, an efficient five-step and two-pot procedure to prepare 4-(difluoromethyl)pyridin-2-amine ( 1 ) has been developed. Noteworthy aspects of this strategy include the avoidance of an amination process using a sealed vessel. Each step of the synthetic route has been optimized, and key intermediates have been isolated and characterized prior to the final two-pot procedure, which has been successfully applied for large-scale production.",10.1021/acs.oprd.9b00312,2019-09-25,0.7112915798268888
Synthesis,An Efficient Enantioselective Synthesis of Florfenicol Based on Sharpless Asymmetric Dihydroxylation,"An efficient and highly enantioselective synthesis of florfenicol­ via a new intermediate threo-dihydroxy ester, with a Sharpless asymmetric dihydroxylation as the key step, is reported. A ring-opening/reduction strategy avoids the formation of a chlorinated byproduct that occurs in Schumacher's phenyloxazoline procedure. The overall yield of florfenicol by this new process is 23% based on 4-(methylsulfonyl)benzaldehyde.",10.1055/s-0031-1289706,2012-02-14,0.7111727047829736
Journal of Organic Chemistry,Enantiospecific Total Synthesis of the Sarpagine Related Indole Alkaloids Talpinine and Talcarpine as Well as the Improved Total Synthesis of Alstonerine and Anhydromacrosalhine-methine via the Asymmetric Pictet−Spengler Reaction,"The enantiospecific total synthesis of talpinine 1 and talcarpine 2 has been accomplished from D-(+)-tryptophan in 13 steps (11 reaction vessels) in 10% and 9.5% overall yields, respectively. Moreover, this synthetic approach has been employed for the improved synthesis of alstonerine 3and anhydromacrosalhine-methine 4 in 12% and 14% overall yield, respectively. A convenient synthetic route for the enantiospecific, stereospecific preparation of the key intermediate (-)-N(a)-H, N(b)-benzyl tetracyclic ketone 15a via the asymmetric Pictet-Spengler reaction on a multihundred-gram scale has been developed. A diastereocontrolled (>30:1) anionic oxy-Cope rearrangement and the intramolecular rearrangement to form ring-E and an N(b)-benzyl/N(b)-methyl transfer reaction also served as key steps. This general approach can now be utilized for the synthesis of macroline/sarpagine related indole alkaloids and their antipodes for biological screening.",10.1021/jo000126e,2000-04-26,0.7109381800400153
Journal of the American Chemical Society,Efficient Synthesis of NK<sub>1</sub> Receptor Antagonist Aprepitant Using a Crystallization-Induced Diastereoselective Transformation,"An efficient stereoselective synthesis of the orally active NK(1) receptor antagonist Aprepitant is described. A direct condensation of N-benzyl ethanolamine with glyoxylic acid yielded a 2-hydroxy-1,4-oxazin-3-one which was activated as the corresponding trifluoroacetate. A Lewis acid mediated coupling with enantiopure (R)-1-(3,5-bis(trifluoromethyl)phenyl)ethan-1-ol afforded a 1:1 mixture of acetal diastereomers which was converted into a single isomer via a novel crystallization-induced asymmetric transformation. The resulting 1,4-oxazin-3-one was converted via a unique and highly stereoselective one-pot process to the desired alpha-(fluorophenyl)morpholine derivative. Interesting and unexpected [1,2]-Wittig and [1,3]-sigmatropic rearrangements were identified during the optimization of these key steps. In the final step, a triazolinone side chain was appended to the morpholine core. The targeted clinical candidate was thus obtained in 55% overall yield over the longest linear sequence.",10.1021/ja027458g,2003-01-30,0.7108710302165467
Journal of Organic Chemistry,Total Synthesis of Brazilin,"Described herein is a highly efficient total synthesis of brazilin from commercially available starting materials in 9 steps with 70% overall yield. Mitsunobu coupling followed by In(III)-catalyzed alkyne-aldehyde metathesis allowed for rapid construction of brazilin core skeleton in quantitative yield. Subsequent modulation of oxidation levels and acid-catalyzed cyclization led to the trimethyl ether of brazilin. Asymmetric dihydroxylation of the key intermediate was also demonstrated, which would permit asymmetric access to (+)-brazilin.",10.1021/jo502745j,2015-01-06,0.7108450294465423
Organic Process Research & Development,"Development of a Scalable Synthetic Route to GSK369796 (<i>N-tert</i>-Butyl Isoquine), a Novel 4-Aminoquinoline Antimalarial Drug","An improved process to the novel 4-aminoquinoline antimalarial GSK369796 is described. Although the initial synthetic route consisted of only two steps from readily available starting materials, the product isolated via the key Mannich reaction was hampered by both low yields and low purity. In addition to instability under the reaction conditions used for the Mannich reaction, the drug substance was found to decompose during attempts to purify by recrystallisation. Reaction conditions were developed that resolved these issues, culminating in the successful production of multi-kg quantities of GSK369796 in >98% a/a purity and in 57% overall yield.",10.1021/op7002776,2008-01-25,0.7107187970498404
European Journal of Organic Chemistry,An Efficient Multigram Synthesis of Alkannin and Shikonin,"Abstract The concise and efficient total syntheses of alkannin ( 1 ) and shikonin ( 2 ), based on the resolution of a key acid intermediate, are achieved with excellent enantiomeric excesses and high overall yields (99 % ee , 15.6 % for 1 and 99.8 % ee , 11.9 % for 2 ). The key steps of the synthetic strategy involve the convenient synthesis and separation of a pair of amide diastereoisomers and the mild hydrolysis of the amide to remove the amine chiral auxiliary, together with an efficient deprotection sequence of the methyl protecting groups.",10.1002/ejoc.201101505,2012-01-11,0.7106206545570032
European Journal of Organic Chemistry,"Asymmetric Synthesis of (–)‐Pterosin N from a Chiral 1,3‐Dioxolanone","Abstract The first asymmetric total synthesis of (–)‐pterosin N from the N , N ‐diisopropyl‐10‐camphorsulfonamide‐derived chiral 1,3‐dioxolanone 11 has been accomplished in 9 steps with 8 % overall yield. The key steps in this synthesis were the highly stereoselective propargylation of 1,3‐dioxolanone 11 to construct the chiral tertiary alcohol moiety, construction of a diene‐ynone by Stille coupling, and an intramolecular Diels–Alder reaction followed by aromatization to finish the synthesis.",10.1002/ejoc.201402234,2014-06-03,0.7105894685363059
Journal of Organic Chemistry,"Enabling, Decagram-Scale Synthesis of Macrocyclic MCL-1 Inhibitor ABBV-467","ABBV-467 is a highly potent and selective MCL-1 inhibitor that was advanced to a phase I clinical trial for the treatment of multiple myeloma. Due to its large size and structural complexity, ABBV-467 is a challenging synthetic target. Herein, we describe the synthesis of ABBV-467 on a decagram scale, which enabled preclinical characterization. The strategy is convergent and stereoselective, featuring a hindered biaryl cross coupling, enantioselective hydrogenation, and conformationally preorganized macrocyclization by C-O bond formation as key steps.",10.1021/acs.joc.3c00939,2023-11-01,0.7105716842746912
Organic Process Research & Development,Kilogram-Scale Synthesis of 11β-Hydroxyandrosterone,"This article describes a robust and large-scale synthesis of the ketosteroid building block 11β-hydroxyandrosterone (2) from cheap and readily available hydrocortisone (1). The initial discovery route, which was conducted on a gram scale and achieved a 3–6% yield over eight steps, is also described. Key to the route redesign was the incorporation of two stereoselective steps setting the desired 5α-H and 3α-OH chiral centers and optimization to minimize chromatographic purification. The process route was then conducted at the kilogram scale and achieved a 21–28% yield over four steps.",10.1021/acs.oprd.4c00084,2024-05-06,0.7105668913911144
Organic Letters,Formal Enantioselective Synthesis of (+)-Estrone,A formal total synthesis of (+)-estrone (4% overall yield; ca. 12 steps) could be achieved via the Torgov diene. An asymmetric allylic substitution is the key step for the construction of the chiral quaternary carbon center of a synthetic intermediate which was converted in four steps to the Torgov diene. [reaction: see text],10.1021/ol063052n,2007-02-13,0.7105545134222974
Tetrahedron,New synthetic route to homooxacalix[n]arenes via reductive coupling of diformylphenols,,10.1016/s0040-4039(00)02336-4,2001-02-01,0.7103960000421359
Synlett,Stereoselective Total Synthesis of (-)-Ovalicin,"A new synthetic route for epoxyketone 3 is described, which is a key intermediate in Barton's synthesis of ovalicin (1), a powerful anti-angiogenetic inhibitor, from commercially available d-ribose. The key reactions involved in this synthesis are ring-closing metathesis, Rubottom oxidation and Corey-Chaykovsky epoxidation. The subsequent transformations are carried out according to Barton's strategy to complete the total synthesis of (-)-ovalicin.",10.1055/s-0029-1219191,2010-01-11,0.7102788105022791
Organic Letters,Asymmetric Total Syntheses of <i>ent</i>-Ascospiroketals A and B,"A new hypothetic biosynthesis of the tricyclic spiroketal core of ascospiroketals A and B is proposed, which guided the development of a novel synthetic strategy for the asymmetric total synthesis of ent-ascospiroketals A and B. The synthesis features an efficient ring contraction rearrangement of the 10-membered lactone to the tricyclic spiroketal cis-fused γ-lactone core, which served as the common intermediate for the synthesis of both ent-ascospiroketals A and B through the Stille coupling reaction at the final step. In addition, seven diastereomers were prepared to conclusively confirm the structure of ent-ascospiroketal B.",10.1021/acs.orglett.6b00796,2016-04-04,0.7102592213588559
Tetrahedron,Asymmetric synthesis of camptothecin alkaloids: A nine-step synthesis of (S)-camptothecin,,10.1016/s0040-4039(00)73492-7,1994-07-01,0.7102199315239285
Organic Process Research & Development,6-(Trifluoromethyl)pyrid-2-one:  Development and Scale-Up of a Ring Synthesis Route Based on Trifluoroacetic Anhydride,"Three routes to 6-(trifluoromethyl)pyrid-2-one involving de novo synthesis of the pyridine ring have been investigated which would potentially allow rapid semi-technical scale manufacture. A route starting from ethyl 4,4,4-trifluoroacetoacetate (β-keto ester route) has been demonstrated. Development of the route was attempted; however, poor yields at a number of stages and scale-up difficulties made this route unattractive for commercial use. A four-stage route starting from trifluoroacetic anhydride and an alkyl vinyl ether (TFAA route) has been developed which gives good yields and productivity for all stages. The final stage of this route is a difficult decarboxylation of a nicotinic acid derivative, but an 80% yield of the required pyridone with a purity of >99.5% could be achieved without a separate purification stage. The route was scaled up to 2000 L, and several hundred kilograms of product was prepared.",10.1021/op970024z,1997-09-01,0.710209456247256
Organic Letters,Addition of Metallo Enolates to Chiral 1-Acylpyridinium Salts:  Total Synthesis of (+)-Cannabisativine,[formula: see text] A novel route to the first asymmetric synthesis of (+)-cannabisativine (1) is described. The total synthesis of 1 was accomplished with a high degree of regio- and stereoselectivity in 19 steps and 9% overall yield.,10.1021/ol0056271,2000-02-15,0.7101686727847959
Tetrahedron,Carbocyclic analogs of C-nucleosides: a key intermediate via a novel and efficient CC ring scission,,10.1016/s0040-4039(01)93278-2,1981-01-01,0.7101390318334149
Journal of Organic Chemistry,Total Synthesis of the Potent Antitumor Polyketide (−)-Callystatin A,A highly convergent and efficient total synthesis of the potent antitumor polyketide (-)-callystatin A is described. The synthesis required 19 steps from N-propionyl oxazolidinone 23 and produced the desired product in 3.5% overall yield.,10.1021/jo050352u,2005-05-12,0.7101242216042045
Tetrahedron,An asymmetric route to total synthesis of the furano lignan (+)-veraguensin,,10.1016/j.tetlet.2010.10.136,2010-11-01,0.7100594473167848
Synthesis,Synthesis of Racemic and Enantiopure Forms of β-Carboline Alkaloid Brevicolline,"Abstract A new total synthesis of the pharmacologically active β-carboline alkaloid brevicolline is described. The new synthetic approach is based on a commercially available and inexpensive starting material and reagents leading to a practical synthesis of the racemic target molecule, the natural (S)-enantiomer, and its antipode. Initially, the construction of the β-carboline skeleton and functionalization at the C(4) position have been accomplished. The formation of dihydropyrrole structural unit was obtained as the result of an Au-catalyzed hydroamination reaction, which was followed by a reduction that led to the chiral intermediate. The synthetic route described here is developed to ensure the sustainable access of the racemic brevicolline in 11 steps with improved 48% overall yield compared to the previously reported methods.",10.1055/s-0041-1737830,2022-02-15,0.7098421845103898
Tetrahedron,An optimized synthesis of the potent and selective Pak1 inhibitor FRAX-1036,,10.1016/j.tetlet.2015.12.059,2015-12-15,0.7098403879043712
Organic Letters,Practical Asymmetric Synthesis of a Selective Endothelin A Receptor (ETA) Antagonist,"[structure: see text]. A practical, chromotography-free asymmetric synthesis was developed for the large scale preparation of an endothelin receptor antagonist 2. This synthesis includes a new efficient process for the preparation of 6-bromo-2,3-dihydrobenzofuran, a stereoselective conjugate addition of an aryllithium followed by stereospecific addition of the Grignard reagent of the top aryl bromide, and an aminophosphate-mediated sterospecific intramolecular enolate alkylation, which led to the formation of the five-membered ring bearing three contiguous asymmetric centers.",10.1021/ol016601s,2001-09-27,0.7097819644864728
Organic Process Research & Development,New and Practical Synthesis of Gedatolisib,"A new, practical, and convergent synthetic route of gedatolisib, an antitumor agent, is developed on a hectogram scale which avoids the Pd coupling method. The key step is adopting 6-(4-nitrophenyl)-1,3,5-triazine-2,4-diamine and 2,2′-dichlorodiethyl ether to prepare the key 4,4′-(6-(4-nitrophenyl)-1,3,5-triazine-2,4-diyl)dimorpholine in 77% yield and 98.8% purity. Gedatolisib is obtained in 48.6% yield over five simple steps and 99.3% purity (HPLC). Purification methods of the intermediates and the final product involved in the route are given.",10.1021/acs.oprd.7b00298,2017-11-30,0.7097296958435108
Organic Process Research & Development,"Scalable Synthesis of ABBV-105 Enabled by Suzuki Coupling with Low Pd Loading, Ru-Catalyzed Asymmetric Hydrogenation, and Acylation Using Impinging Jet","Evolution of a synthetic process to prepare ABBV-105, a Bruton’s tyrosine kinase (BTK)-inhibitor, on multikilogram scale is described. The first-generation route utilized chiral resolution of the penultimate intermediate ( 7 ). Either Bartoli or Leimgruber–Batcho indole synthesis was used to prepare the key intermediate, indole boronate ester ( 23 ). As the demand for the API increased, the first-generation route was found to be low-yielding and expensive. It required column chromatography, had multiple alerting structures from the mutagenic impurity assessment, and suffered from lack of robustness. In the second-generation route a novel Ru-catalyzed asymmetric hydrogenation of 1,2,5,6-tetrahydropyridine ( 21 ) was developed to establish the stereocenter. Compound 21 was accessed via Suzuki coupling of 23, prepared by Friedel–Crafts acylation, with vinyl bromide ( 24 ) in the presence of very low loading of a Pd catalyst (0.15 mol % Pd). Finally, the penultimate intermediate ( 7 ) was coupled with acryloyl chloride using an impinging jet to prepare the API. Detailed kinetic and mechanistic work was conducted to control the persistent impurities formed in the API step. The second-generation route was robust, chromatography-free and high-yielding with low mutagenic liability.",10.1021/acs.oprd.4c00117,2024-07-17,0.709659889694097
Tetrahedron,Carotenoid synthesis with 4-(t-butylthio)-3-buten-2-one. A new synthesis of isorenieratene,,10.1016/s0040-4039(01)86423-6,1979-01-01,0.7095495428629492
Tetrahedron,Cyclopalladated imines in synthesis 2 : a new synthesis of isoquinolines,,10.1016/s0040-4039(00)88725-0,1982-01-01,0.7095495428629492
Journal of Organic Chemistry,Synthesis of 3-Aminopyrazinone Mediated by 2-Pyridylthioimidate−ZnCl<sub>2</sub> Complexes. Development of an Efficient Route to a Thrombin Inhibitor,"A six-step preparation of thrombin inhibitor drug candidate 1 from pyrazinone 7 in 47% overall yield is described. The problem of low reactivity between weak amine nucleophile 4 and poor electrophile 3-bromopyrazinone 17 was overcome with the use of pyridinylthioimidate 27 in the presence of ZnCl(2) to afford adduct 3 in high yield. Several zinc complexes were characterized by solution and solid-state NMR and X-ray crystallographic analyses, and provided insight into the reaction mechanism. Preparation of pyridine N-oxide amine 4 was accomplished via a selective oxidation of the corresponding pyridinylamine 6. Pyridinylthioimidate 27 was prepared from pyrazinone 7 via a two-step one-pot process in near quantitative yield. Chlorination of the pyrazinone ring in 3 followed by hydrolysis and amide coupling completed the synthesis of 1. This chromatography-free synthesis was used successfully to prepare multikilogram quantities of the drug with reproducibility and high purity.",10.1021/jo034835e,2003-10-11,0.709516873217699
Organic Process Research & Development,Manufacturable Process of a Novel EGFR Inhibitor (Larotinib) for the Treatment of ESCC,"The development of an efficient synthetic process for a clinical candidate Larotinib ( 4 ), which is an epidermal growth factor receptor (EGFR) inhibitor for the treatment of esophageal squamous cell carcinoma (ESCC), is reported for scale-up. The process used 3,4-dihydro-7-methoxy-4-oxoquinazolin-6-yl acetate ( 12 ) as the regulatory starting material and provided a stable and industrializable intermediate chloroquinazoline 11 under the process control. Further optimization of the process obviously improved the reaction yield and reduced the impurity level including alkyl halide potential genotoxic impurities (PGIs), at the same time avoiding the use of laborious and time-consuming column chromatography. More than 110 kg of Larotinib ( 4 ) in one batch can be finally produced stably for clinical research. Compared to our initial synthetic route in preclinical research, the overall yield of this optimized process increased significantly from 16.2 to 55.6%.",10.1021/acs.oprd.2c00059,2022-05-09,0.7095062778333352
Journal of Organic Chemistry,Formal Total Synthesis of Pericoannosin A,"A concise formal total synthesis of pericoannosin A, by the synthesis of an advanced intermediate of pericoannosin A, was achieved in eight steps from commercially available isoprene in a 21.7% overall yield. Key transformations for this expedited route include an enantioselective organocatalytic Diels–Alder reaction to construct the C ring, a diastereoselective reduction (under Felkin–Ahn control), and a hydroboration/oxidation sequence for chain homologation. This work represents the second synthetic effort toward pericoannosin A, the only reported natural product based on a hexahydro-1 H -isochromen-5-isobutylpyrrolidin-2-one core.",10.1021/acs.joc.9b01846,2019-08-22,0.7094360196921633
Synlett,Synthesis of cis-5-Trifluoromethylproline from l-Glutamic Acid,The diastereoselective synthesis of cis -5-trifluoromethylproline (5-Tfm-Pro) from l -glutamic acid is described. 5-Tfm-Pro could be obtained through a seven-step linear sequence. Trifluoromethylation of the glutamic-derived ester or aldehyde and subsequent reduction of the cyclic imine are the key steps in the synthesis.,10.1055/s-0033-1340553,2014-01-14,0.7093880975849836
Journal of the American Chemical Society,Enantioselective Synthesis of Stephacidin B,"We describe an enantioselective synthetic route to the antiproliferative alkaloid stephacidin B (1) proceeding in 18 steps and 4.0% yield from 4,4-(ethylenedioxy)-2,2-dimethylcyclohexanone (3). Key features of the synthetic sequence include the use of the Corey-Bakshi-Shibata (CBS) reduction to introduce asymmetry early in the synthetic route, use of the novel electrophile N-(tert-butoxycarbonyl)-5-(isopropylsulfonyloxymethyl)-2,3-dihydropyrrole in a stereoselective enolate alkylation, a diastereoselective Strecker-type addition of hydrogen cyanide to an N-Boc enamine substrate in the solvent hexafluoroisopropanol, platinum-catalyzed nitrile hydrolysis under neutral conditions, cyclization of an acylamino radical intermediate to form the diketopiperazine core of stephacidin B, and implementation of a convergent procedure for introduction of the key 3-alkylidene-3H-indole 1-oxide functional group in the final stage of the route to prepare the structure 2, previously proposed to be the fungal metabolite avrainvillamide (17 steps, 4.2% yield). We observed that synthetic (-)-2 dimerized in the presence of triethylamine to form (+)-stephacidin B (>95%). We also obtained evidence that 2 can form 1 under mild conditions, and that 2 reacts with nucleophiles, such as methanol, by conjugate addition.",10.1021/ja0510616,2005-03-24,0.7093446831642876
Organic Letters,Short and Versatile Route to a Key Intermediate for Lactacystin Synthesis,"[reaction: see text] A key intermediate 14 for the synthesis of lactacystin 1 has been constructed in four steps and 33% overall yield. The key steps involve cyclization of a suitably functionalized glutamic acid derivative and concomitant alkylation of the resulting beta,beta-diketoester system, C-acylation of the cyclic alpha-amidoketone 9, and decarboxylbenzylation of 12. Alkylation of a related beta,beta-diketoester 5 was additionally achieved with several electrophiles.",10.1021/ol027387q,2003-01-15,0.7093099178291492
Journal of Organic Chemistry,Stereocontrolled and Convergent Total Synthesis of Amphidinolide T3,"Stereocontrolled and convergent total synthesis of amphidinolide T3 has been described. A retrosynthetic scheme was constructed that led to the recognition of readily available and enantiomerically related compounds as starting materials for the total synthesis of amphidinolide T3. Thus, the two key building blocks 6 and 7 were defined as subtargets and synthesized in optically active forms. The C1-C12 fragment 6 was derived from commercially available D-glutamic acid or its synthetically equivalent (R)-5-hydroxymethyltetrahydrofuran-2-one 16 as starting material involving highly diastereoselective asymmetric allylation as a key step. The C13-C21 fragment 7 was efficiently synthesized in high yield through the dithiane coupling of the segment 10 and iodide 11, followed by subsequent deprotection and Petasis olefination. Eventually, assembly of the fragment aldehyde 6 and dithiane 7 along with C-C bond formation, a two-step oxidation-reduction sequence, selective macrolactonization, and functional transformation furnished the convergent total and formal synthesis of amphidinolide T3 and T4, and this approach also provides a flexible and practical synthesis of amphidinolide T macrolides.",10.1021/jo0605086,2006-05-17,0.7092827788702435
Organic Letters,Enantioselective Total Synthesis of (+)-Amabiline,"The first total synthesis of (+)-amabiline, an unsaturated pyrrolizidine alkaloid from Cynoglossum amabile, is reported. This convergent, enantioselective synthesis proceeds in 15 steps (10-step longest linear sequence) in 6.2% overall yield and features novel methodology to construct the unsaturated pyrrolizidine or (-)-supinidine core.",10.1021/ol300466a,2012-03-20,0.7092109650925795
Tetrahedron,"An improved and scalable synthesis of N-(5-(4-cyanophenyl)-3-hydroxypicolinoyl)glycine, a promising PHD2 inhibitor for the treatment of anemia",,10.1016/j.tetlet.2015.07.013,2015-07-09,0.7090876939635855
Organic Process Research & Development,Evolution of the Synthetic Process to an Advanced GPR40 Agonist,"Herein we describe a series of synthetic efforts to prepare an advanced GPR40 agonist (compound 1 ), with focus on phase-appropriate processes that circumvented key reagents with short supply in the original synthesis. The key transformations refined for large-scale production were an asymmetric aldol reaction, O -alkylation of an unstable intermediate, selective ( Z )-olefination, and reduction of a Weinreb amide to aldehyde. Additionally, the new route circumvented stability issues of the core pyrrolidine fragment through de novo synthesis, achieving high d.r. during ring formation. The new improved route was efficiently scaled up to prepare more than 100 g API for toxicology studies.",10.1021/acs.oprd.3c00433,2024-01-02,0.7090815992665211
Journal of Organic Chemistry,Evolution of a Strategy for the Total Synthesis of Psymberin,"values below 2.5 nM. Its complex molecular architecture, notable biological activity, and scarcity in nature have made psymberin a compelling target for synthetic chemists since its discovery. This account outlines our efforts toward the total synthesis of psymberin, highlighting two distinct generations of synthetic strategies. The first-generation approach featured several innovative transformations, including a transannular Michael addition followed by lactone reduction to establish the 2,6-trans-tetrahydropyran core, a diastereoselective iodocarbonate cyclization induced by iodine bromide (IBr), and a Diels-Alder/aromatization sequence to construct the highly substituted aromatic ring system. The second-generation synthesis adopted a more efficient and convergent strategy. Key advances included a Heck coupling to join a sterically hindered aryl fragment with a terminal alkene, followed by a palladium-catalyzed cyclization to form the isocoumarin scaffold. This revised route reduced the longest linear sequence by seven steps compared to the original synthesis, representing a significant improvement in overall efficiency. Together, these strategic developments─both designed and serendipitous─highlight the synthetic challenges and opportunities presented by psymberin's complex structure. The approaches described herein provide valuable insights for the synthesis of structurally related natural products and other architecturally sophisticated molecules.",10.1021/acs.joc.5c02064,2025-12-01,0.7090624539525928
Journal of Organic Chemistry,Total Synthesis of Bafilomycin A<sub>1</sub>,"The highly stereoselective total synthesis of the macrolide antibiotic, bafilomycin A(1) (1), the first specific potent inhibitor of vacuolar H(+)-ATPase, has been achieved by a convergent route involving the synthesis and coupling of its 16-membered tetraenic lactone and beta-hydroxyl hemiacetal side-chain subunits. The C1-C17 16-membered lactone aldehyde 2 was synthesized through the coupling of the C5-C11 vinyl iodide 4 and the C12-C17 vinylstannane 5, followed by construction of the C1-C4 diene and macrolactonization. The aldol coupling of 2 and the C18-C25 ethyl ketone 3 followed by desilylation provided 1, which was identical with natural bafilomycin A(1). The key synthetic segments 3-5 were effectively synthesized from the readily available chiral materials, D-glucose, ethyl (S)-lactate, and methyl (S)-3-hydroxy-2-methylpropionate, respectively.",10.1021/jo970314d,1997-05-01,0.7090304008341278
Journal of Organic Chemistry,Total Synthesis of Sieboldine A,"Previously, we have finished the total synthesis of lycojaponicumin A ( 2 ) via development of an efficient synthetic strategy using semipinacol rearrangement as a key step. In order to further demonstrate the generality of this synthetic route, herein, we report the total synthesis of another fawcettimine-type alkaloid sieboldine A ( 1 ) from the same intermediate, which possesses an A/B/D tricyclic ring system and vicinal quaternary centers of 1 . The synthesis features late-stage site-selective redox reactions, Schmidt glycosylation cyclization, and highly selective transformations.",10.1021/acs.joc.0c01660,2020-08-17,0.7090290329849684
Organic Letters,"Gram-Scale Synthesis of (+)-Spongistatin 1: Development of An Improved, Scalable Synthesis of the F-Ring Subunit, Fragment Union, and Final Elaboration","In a quest to develop an effective, scalable synthesis of (+)-spongistatin 1 ( 1), we devised a concise, third-generation scalable synthesis of (+)- 7, the requisite F-ring tetrahydropyran aldehyde, employing a proline-catalyzed cross-aldol reaction. Subsequent elaboration to (+)-EF Wittig salt (+)- 3, followed by union with advanced ABCD aldehyde (-)- 4, macrolactonization and global deprotection permitted access to >1.0 g of totally synthetic (+)-spongistatin 1 ( 1).",10.1021/ol801792k,2008-08-28,0.7089310703778162
Synthesis,A New Laboratory Scale Synthesis for the Anticancer Drug 3′<i>-C-</i>Ethynylcytidine,"A new synthetic route for the preparation of larger quantities of the anticancer nucleoside analogue 3′-<em>C</em>-ethynylcytidine is described. Starting from cytidine which was orthogonally protected in three steps, the ketonucleoside analogue as the key intermediate was obtained through oxidation of the unprotected 3′-hydroxy group. Stereoselective addition of the trimethylsilyl-protected acetylide residue at the 3′-carbonyl group followed by a complete deprotection afforded 3′-<em>C</em>-ethynylcytidine in an overall yield of 24% in seven steps.",10.1055/s-2002-35221,2002-01-01,0.7088671009359753
Synlett,"Thermolysis of N-aryl-β-chlorovinylimines: Synthesis of 7,13-Dibutyl-4-phenanthridino[3,2-a]-4-phenanthridino[2,3-j]anthracene, a novel cavity shaped nonacyclic diazaarene",All articles of this category An efficient synthesis of the title compound in five steps is described starting from the diketone ( 1 ) via thermolysis of the bis-chlorovinylimine derivative ( 3 ) as the key step. chloroaldehydes - N-aryl β-chlorovinylimines - thermolysis - cavity shaped molecule - nonacyclic diazaarene,10.1055/s-1997-1534,1997-09-01,0.7088235157471006
Journal of Organic Chemistry,De Novo Asymmetric Syntheses of Muricatacin and Its Analogues via Dihydroxylation of Dienoates,"A short and highly efficient route to both enantiomers of muricatacin as well as the C-5-epimer has been developed. The key to the overall transformation is the highly regio- and enantioselective Sharpless asymmetric dihydroxylation of an (E,Z)-dienoate. The highly efficient stereoselective synthesis prepares (-)-muricatacin in seven steps and 66% overall yield.",10.1021/jo061057s,2006-07-28,0.7088122097778662
Organic Letters,"Efficient Synthesis of Empagliflozin, an Inhibitor of SGLT-2, Utilizing an AlCl<sub>3</sub>-Promoted Silane Reduction of a β-Glycopyranoside","An efficient production synthesis of the SGLT-2 inhibitor Empagliflozin (5) from acid 1 is described. The key tactical stage involves I/Mg exchange of aryl iodide 2 followed by addition to glucono lactone 3 in THF. Subsequent in situ treatment of the resulting lactol with HCl in MeOH produces β-anomeric methyl glycopyranoside 4 which is, without isolation, directly reduced with Et3SiH mediated by AlCl3 as a Lewis acid in CH2Cl2/MeCN to afford 5 in 50% overall yield. The process was implemented for production on a metric ton scale for commercial launch.",10.1021/ol501755h,2014-07-25,0.7086757635784203
Synthesis,"Development of an Efficient Synthesis toward a 4,4-Difluoropiperidine Intermediate Bearing a Pyridine N-Oxide Motif at the Carbon Stereocenter","Abstract The synthesis of a 4,4-difluoropiperidine intermediate, a key component of an MRGPRX2 antagonist, is challenging due to the presence of a gem-difluoro moiety adjacent to a stereocenter which also bears a reactive pyridine N-oxide motif. The initial discovery chemistry route required chiral supercritical fluid chromatography (SFC) at the end of the synthesis to provide enantiopure product. XtalFluor-E was used for deoxyfluorination on a ketone adjacent to a p-pyridylmethyl position, resulting in very low yields due to the elimination of HF. After several unsuccessful attempts for a de novo asymmetric synthesis, we focused our attention on the process development for a more practical synthesis than the existing route. A much higher yielding deoxyfluorination was enabled by SF4 and HF. Furthermore, the chiral SFC was replaced by an efficient classical resolution at a much earlier stage of the synthesis, taking advantage of the basicity of the pyridine moiety before oxidation to the pyridine N-oxide. Although not all stages have been scaled up in the plant scale, the new synthesis is much more practical and has improved the overall yield from 12% to 23% for this challenging molecule.",10.1055/s-0043-1773542,2025-04-17,0.7085505334004789
Journal of Organic Chemistry,Asymmetric Total Synthesis of (−)-Saframycin A from<scp>l</scp>-Tyrosine,"The asymmetric total synthesis of (-)-saframycin A, a natural antitumor product of the tetrahydroisoquinoline antitumor antibiotics family, has been accomplished by employing L-tyrosine as the starting chiral building block in 24 steps for the longest linear sequence in an overall yield of 9.7%. The key steps in the synthesis involve stereoselective intermolecular and intramolecular Pictet-Spengler reactions, which induced the correct stereochemistry at C-1 and C-11, respectively. The selective protection-deprotection protocol of an amino group in the two-step transformation from intermediate 10 to 12 and a hydroxyl group in the first two steps resulted in both high selectivity and efficiency of the synthetic route.",10.1021/jo200758r,2011-05-25,0.7085040779650054
European Journal of Organic Chemistry,"Practical Synthesis of Elacestrant, an FDA‐Approved Selective Estrogen Receptor Degrader","Herein, we report an efficient and scalable synthesis of the core skeleton of elacestrant, a selective estrogen receptor degrader used in breast cancer treatment. The present synthesis features simple synthetic transformations, involving one‐pot conversion of 6‐hydroxy‐1‐tetralone into a cyclic olefin followed by copper‐catalyzed arylation of the cyclic olefin (iodometathesis) with a diaryliodonium salt as a key strategy to achieve the core skeleton on a gram scale. This procedure was extended to the total synthesis of (±)‐elacestrant by employing two different coupling strategies: reductive amination of an aldehyde and nucleophilic substitution of a bromo compound with the core skeleton.",10.1002/ejoc.202501030,2025-12-09,0.7084845578344201
Tetrahedron,A novel and efficient route to prostanoid intermediates,,10.1016/s0040-4039(01)80309-9,1989-01-01,0.7083962437666259
Synthesis,Synthesis of 2-Alkynyl Tetramethylphosphorodiamidates; A New Route to 1-Bromo-2-alkynes,,10.1055/s-1974-23426,1974-01-01,0.7083767578296134
Organic Letters,"Total Synthesis of Aaptamine, Demethyloxyaaptamine, and Their 3-Alkylamino Derivatives",A simple and efficient synthetic route for preparing the benzonaphthyridine framework is reported. Only seven steps are needed for the assembly of 3-alkylamino aaptamine from inexpensive isoquinoline 6 by this route with about 20% overall yield. The two key steps are a novel palladium-catalyzed reductive cyclization with Mo(CO) 6 as reductant to form aaptamine and demethyloxyaaptamine and a hydrogen-bond-mediated oxidative alkylamination to account for the complete regioselectivity.,10.1021/acs.orglett.9b00183,2019-02-18,0.7083251604932709
Journal of the American Chemical Society,Nine-Step Enantioselective Total Synthesis of (+)-Minfiensine,An enantioselective total synthesis of the Strychnos alkaloid (+)-minfiensine has been accomplished. Prominent features of this synthesis include (i) a new enantioselective organocatalytic Diels-Alder/amine cyclization sequence to build the central tetracyclic pyrroloindoline framework in four steps from commercial materials and (ii) a 6-exo-dig radical cyclization to forge the final piperidinyl ring system. This total synthesis of (+)-minfiensine was completed in nine chemical steps and 21% overall yield.,10.1021/ja906472m,2009-09-02,0.7082829318429397
Journal of Organic Chemistry,A Highly Convergent Synthesis of a Fibrinogen Receptor Antagonist,"A practical multikilogram synthesis of 2( S )-[( p -toluenesulfonyl)amino]-3-[[[5,6,7,8-tetrahydro-4-oxo-5-[2-(piperidin-4-yl)ethyl]-4 H -pyrazolo[1,5- a ][1,4]diazepin-2-yl]carbonyl]amino]propionic acid pentahydrate ( 1 ), an oral fibrinogen receptor antagonist, is described. The nine-step convergent process, which afforded 1 in 37% overall yield, included pyrazole 5a and N -tosylaminoalanine 16 as key fragments. Pyrazole 5a was obtained from pyrazole-3,5-dicarboxylic acid by esterification with MeOH, alkylation/cyclization with 3-bromopropylamine, and Michael addition with 4-vinylpyridine. N -Tosylaminoalanine 16 was prepared by tosylation of asparagine, Hofmann reaction, and benzyl esterification. Saponification of pyrazole 5a, coupling of the acid with N -tosylaminoalanine 16, and Pd-catalyzed hydrogenolysis and pyridine reduction completed the synthesis.",10.1021/jo990644t,1999-09-30,0.7082495673715924
Organic Letters,"Enantioselective Synthesis of (−)-Dihydrocodeine and Formal Synthesis of (−)-Thebaine, (−)-Codeine, and (−)-Morphine from a Deprotonated α-Aminonitrile","The α-benzylation of a deprotonated bicyclic α-aminonitrile, followed by Noyori's asymmetric transfer hydrogenation combined with the Grewe cyclization onto a symmetrical A-ring precursor, are the key steps of a short and high-yielding enantioselective synthesis of the morphinan (-)-dihydrocodeine. This compound can be converted to (-)-thebaine in high yield by known transformations, while (-)-codeine and (-)-morphine are available from an advanced intermediate.",10.1021/ol5023849,2014-10-01,0.708122417400469
Synthesis,Synthesis of the Sugar Building Block of Bicyclo-RNA,"We present the novel synthesis of two sugar units that are central intermediates for the formation of members of the bicyclo-DNA and -RNA family. The synthesis starts from commercially available 1,2:5,6-di-O-isopropylidene-α-d-glucofuranose. The key step involves the elaboration of a carbocyclic ring in a furanoside by rhodium(I)-catalyzed hydroacylation. Via this pathway, one of the sugar units is available in 8 steps and in an overall yield of 27%, while its deoxy derivative is obtained in 11 steps, which is 5 steps fewer than in our previous synthesis of this compound.",10.1055/s-0029-1218650,2010-01-25,0.7080235240518556
Organic Letters,Self-Regeneration of Stereocenters:  A Practical Enantiospecific Synthesis of LFA-1 Antagonist BIRT-377,"[reaction: see text] An efficient enantiospecific synthesis of the LFA-1 antagonist BIRT-377 has been achieved in 43% overall yield in eight steps. The key transformations involve the stereospecific formation of the trans imidazolidinone 7, subsequent alkylation, and the efficient hydrolysis of disubstituted imidazolidinone 9. The process is practical, robust, and cost-effective; it has been successfully implemented in the pilot plant to produce multikilogram quantities of the drug BIRT-377.",10.1021/ol000147v,2000-08-18,0.7080058647228002
Tetrahedron,"Palladium-catalyzed stereocontrolled cyclization of 1,3-diene monoepoxide: A route to a new synthetic intermediate for de-ab-cholestane derivative.",,10.1016/s0040-4039(00)83905-2,1986-01-01,0.7080057616374711
Tetrahedron,The Pummerer cyclization route to the ibophyllidine alkaloids. Total synthesis of (±)-deethylibophyllidine,,10.1016/s0040-4039(00)73377-6,1994-06-01,0.7079936076287136
European Journal of Organic Chemistry,Carbazomycin G: Method Development and Total Synthesis,"A novel total synthesis leading to the carbazole alkaloid carbazomycin G was designed and developed. The outlined synthetic route is composed of twelve synthetic steps including the transformations of the initial simple substrate and intermediates. To realize the designed synthesis, in total six new synthetic methods were developed and implemented to provide the target molecule in an overall yield of 8.3 %.",10.1002/ejoc.201800359,2018-03-07,0.7079622002600088
Journal of Organic Chemistry,An Efficient and Diastereoselective Synthesis of PSI-6130: A Clinically Efficacious Inhibitor of HCV NS5B Polymerase,"R7128 is the prodrug of 2'-deoxy-2'-fluoro-2'-C-methylcytidine (PSI-6130), a potent and selective inhibitor of HCV NS5B polymerase. Currently, R7128 is in clinical trials for the treatment of HCV infection. To support clinical development efforts, we needed an efficient and scalable synthesis of PSI-6130. We describe an improved, diastereoselective synthetic route starting with protected d-glyceraldehyde. No chiral reagents or catalysts were used to produce the three new contiguous stereocenters. Introduction of fluorine at the C-2 tertiary carbon was accomplished in a highly regio- and stereoselective manner through nucleophilic substitution on a cyclic sulfate. Scale-limiting chromatographic purifications were eliminated through the use of crystalline intermediates.",10.1021/jo901345j,2009-07-30,0.7079125679958378
Organic Process Research & Development,Practical Asymmetric Synthesis of a Bicyclic Pyrrolidinol,"The “butterfly-shaped” bicyclic pyrrolidinol ((2 R,7a S )-2-fluorotetrahydro-1 H -pyrrolizin-7a(5 H )-yl)-methanol ( 1 ) is a key building block for drug candidates, and its practical chemical synthesis remains elusive. As such, an asymmetric synthesis for ((2 R,7a S )-2-fluorotetrahydro-1 H -pyrrolizin-7a(5 H )-yl)-methanol ( 1 ) that is amenable for scale-up has been developed. The newly optimized process utilizes readily available N -Boc- trans -4-hydroxy- l -proline methyl ester ( 8 ) to establish the challenging stereogenic center bearing the fluoride. Subsequent diastereoselective α-alkylation was achieved by leveraging Seebach’s self-regeneration of stereochemistry (SRS) methodology, which has been exploited for the synthesis of proline derivatives. Finally, intramolecular cyclization/deprotection cascade and carbonyl reduction afford the bicyclic pyrrolidinol 1 in nine linear steps from compound 8 . This process significantly reduces the overall production sequence and allows the preparation of product 1 on a multikilo scale with a 40% overall yield and perfect control of chirality (>99% ee and de).",10.1021/acs.oprd.2c00200,2022-10-04,0.707869802863772
Journal of Organic Chemistry,An Efficient and Large-Scale Enantioselective Synthesis of PNP405:  A Purine Nucleoside Phosphorylase Inhibitor,"An efficient and large-scale enantioselective synthesis of PNP405 (1), a purine nucleoside phosphorylase inhibitor, is described. This synthesis of 1 involved eight steps starting from o-fluorophenylacetic acid with a 21.6% overall yield and >99.5% enantiopurity. The key stereogenic center with (R)-configuration was created using Evans' asymmetric alkylation methodology. This synthesis also features the racemization-free reductive removal of the chiral auxiliary in 5 using sodium borohydride, protection of the gamma-cyano alcohol 6 as the trityl ether by a new water-assisted tritylation with trityl chloride and triethylamine or with trityl alcohol and catalytic trifluoroacetic acid, and an efficient one-pot cyclo-guanidinylation of 10 using cyanamide as the guanidinylating agent.",10.1021/jo020256i,2002-08-27,0.7077586631423697
Organic Process Research & Development,Process Development and GMP Production of a Potent NAE Inhibitor Pevonedistat,"A practical synthesis of a novel NEDD8-activating enzyme (NAE) inhibitor pevonedistat (MLN4924) is described. Key steps include an enantioselective synthesis of an amino-diol cyclopentane intermediate containing three chiral centers and a novel, regioselective sulfamoylation using N -( tert -butoxycarbonyl)- N -[(triethylenediammonium)sulfonyl]azanide. The linear process, involving six solid isolations, has been carried out in multiple cGMP productions on 15–30 kg scale to produce pevonedistat in 98% (a/a) chemical purity and 25% overall yield.",10.1021/acs.oprd.5b00209,2015-08-14,0.7077552853131694
Organic Process Research & Development,Process Development and Scale-Up of the PPAR Agonist NNC 61-4655,"A scalable synthetic route of the nonselective but PPARα-preferring potent PPAR agonist NNC 61 - 4655 aimed for treatment of type 2 diabetes was developed. The synthetic pathway comprises the convergent synthesis and coupling of the two key intermediates E -5-(chloropent-3-en-1-ynyl)benzene 8 (prepared in a five-step synthesis in 18% overall yield) and ( S )-2-ethoxy-3-(4-hydroxyphenyl)propanoic acid isopropyl ester 9 . The 2-aminoethanol salt of NNC 61 - 4655 was selected in a preclinical salt selection program as the appropriate salt form for further development. More than 900 g of NNC 61 - 4655, 2-aminoethanol was finally synthesized under GMP in 98.7% purity. In comparison to the original medicinal chemistry route, starting from phenylpropargyl aldehyde 1, the overall yield towards NNC 61 - 4655 could be enhanced from 24 to 37%. An improved scalable two-step synthesis for 8 was developed on a laboratory scale (≥33−35% overall yield) shortly after the GMP batch.",10.1021/op034048j,2004-04-22,0.707748202047391
Organic Process Research & Development,A Convergent Kilogram-Scale Synthesis of the PPARα Agonist LY518674:  Discovery of a Novel Acid-Mediated Triazolone Synthesis,"The first kilogram-scale synthesis of the PPARα agonist LY518674 ( 1 ) is described. The de novo convergent synthetic approach involved coupling of two rapidly assembled components, triazolone formation via a novel acid-promoted cyclization reaction, and final step saponification, delivering the compound in 32.5% overall yield via eight total steps with a six-step longest linear sequence. A regioselective alkylation on the dianion of 4-hydroxyphenylbutyric acid allowed the direct preparation of one of the convergent coupling partners, carboxylic acid 12, and an unusual solvent effect enabled the installation of a urea group on a protected hydrazine, permitting the regiospecific preparation of the other coupling partner, semicarbazide mesylate 17 . Sulfonic acids were found to effect the desired triazolone ring formation, affording 25 from the coupled precursor acyl semicarbazide 23 . Following saponification of 25 to 1, a wide solubility differential between ethyl acetate extracts of 1 and solutions of 1 in anhydrous ethyl acetate was harnessed in the final crystallization step to deliver the final compound in high yield and purity. The novel acid-mediated triazolone formation was further evaluated on a range of additional substrates, showing the new methodology to be largely complementary to existing base-mediated triazolone syntheses.",10.1021/op700040v,2007-04-06,0.7077371155635236
Tetrahedron,"Synthesis of 1s,2r,3s,4r,5r-methyl[2,3,4-trihydroxy-5-(hydroxymbthyl)cyclopentyl]amine: a potent α-mannosidase inhibitor",,10.1016/s0040-4039(00)97253-8,1990-01-01,0.7076493042244755
Organic Process Research & Development,Process Development and Scale-Up of the SOS1 Inhibitor MRTX0902,"High Resolution Image Download MS PowerPoint Slide MRTX0902, a novel SOS1 inhibitor, is currently being evaluated in phase I trials for the treatment of cancer. The complexity of the molecule, which contains a pyrido[3,4- d ]pyridazine core and a chiral amine moiety, makes it a challenging target to prepare on a multi-kilogram scale to support clinical development studies. An efficient and scalable synthesis of the key intermediate 4-methyl-7-morpholinopyrido[3,4- d ]pyridazin-1(2 H )-one and a much improved end-game for MRTX0902 were developed.",10.1021/acs.oprd.3c00030,2023-05-22,0.7076487494373241
Tetrahedron,Concise synthesis of (±)-gomadalactone A,"We report the synthesis of (±)-gomadalactone A, a contact sex pheromone of the white-spotted longicorn beetle ( Anoplophora malasiaca ). The synthesis employs Vassilikogiannakis' one-pot, photo-driven cyclopentenone synthesis from a furan derivative, followed by lactonization, to efficiently construct a distinctive 3-oxabicyclo[3.3.0]octane framework. This eleven-step process starts from methyl 2-furylacetate, produced (±)-gomadalactone A in an overall yield of 1 %. • Synthesis of (±)-gomadalactone A. • Employs Vassilikogiannakis' one-pot, photo-driven cyclopentenone synthesis. • Efficient construction of unique 3-oxabicyclo[3.3.0]octane structure achieved. • Required synthetic steps were significantly reduced. • Diastereomeric bicyclic lactone with potential for synthesis of gomadalactone B.",10.1016/j.tetlet.2025.155623,2025-04-29,0.7075854281850135
Organic Process Research & Development,"Development of a Factory Process for Omecamtiv Mecarbil, a Novel Cardiac Myosin Activator","The development of a factory process to manufacture the novel cardiac myosin activator omecamtiv mecarbil ( 1 ) is described. Omecamtiv mecarbil is prepared via the convergent synthesis and coupling of two key fragments, aniline 2 and carbamate 4-HCl, which serves as a masked isocyanate. To enable practical access to aniline 2, reduction of the corresponding nitroaromatic was designed to control potential mutagenic impurities. Key to the efficient preparation of 2 was the benzylic bromination of 8 followed by selective debromination of a gem -dibromide byproduct and subsequent alkylation with 5-phosphate . Overall, the longest linear sequence consists of six steps, including a final salt formation step to afford the drug substance in 55% overall yield. Because of poor performance of the original free-base form of the drug substance in modified-release formulations, an improved dihydrochloride hydrate form was developed to aid drug product performance and manufacturability.",10.1021/acs.oprd.9b00200,2019-07-15,0.7075697838233901
Organic Process Research & Development,Development of a Scalable Enantioselective Synthesis of JAK Inhibitor Upadacitinib,"Process development of a six-stage synthesis of upadacitinib, a JAK1 inhibitor, is described. It is highlighted by an enantioselective and diastereoselective hydrogenation of a tetrasubstituted olefin to set the two pyrrolidine stereocenters. Preparation of the main fragments and strategies to link them together, optimization of the imidazole cyclization, and in-depth understanding of the formation of the urea moiety at the final stage are discussed.",10.1021/acs.oprd.1c00287,2021-09-28,0.7075232938559441
Journal of Organic Chemistry,Synthesis of Highly Functionalized Hydrindanes via Sequential Organocatalytic Michael/Mukaiyama Aldol Addition and Telescoped Hydrozirconation/Cross-Coupling as Key Steps: En Route to the AB System of Clifednamides,"The AB ring systems of the clifednamide family, polycyclic tetramate macrolactames (PoTeMs), were prepared by a new, convergent approach employing an intramolecular Diels-Alder (IMDA) reaction. Key steps comprise an organocatalytic Michael addition (>90% enantiomeric excess (ee)), a Mukaiyama aldol reaction for the convergent installation of a diene moiety, and a telescoped hydrozirconation/cross-coupling grafting an enone. The following IMDA furnished a highly functionalized hydrindane (diastereomeric ratio (dr) = 91:1) with the same configuration as the clifednamide scaffold. Advantages of this route are only one required protecting group, 13% overall yield over 9 steps (reduced from previously 17 steps/1.3% overall), and the potential access to the key intermediates in the clifednamide biosynthesis.",10.1021/acs.joc.1c00580,2021-05-20,0.7075202247273544
Tetrahedron,"An efficient and tunable route to AG7088, a rhinovirus protease inhibitor",,10.1016/j.tetlet.2004.08.179,2004-09-24,0.7074475276054651
Journal of Organic Chemistry,Asymmetric Synthesis of a Chiral Building Block for Cyclopentanoids:  A Novel Enantioselective Synthesis of Preclavulone A,"A new asymmetric approach to the hydroxylactone (+)-(3aR,4R,6aS)-4-(hydroxymethyl)-3a,4-dihydro-3H-cyclopenta[b]furan-2(6aH)-one (1), a key synthetic building block for cis-1,2-disubstituted five-membered ring derivatives (i.e., isoprostanes, jasmonates, and clavulones), has been described. A remarkable control of the absolute and relative configuration of the three stereocenters was achieved. Thus, the use of the Trost's asymmetric allylic alkylation strategy secured highly enantioenriched (R)-3-(nitromethyl)cyclopent-1-ene (13), which was smoothly converted to (R)-cyclopent-2-enecarboxylic acid (15) in excellent yield and high enantiomeric purity (>98% ee). 6-exo-trig atom-transfer radical cyclizations of ((R)-cyclopent-2-enyl)methyl 2-iodoacetate (12) produced exclusively the desired cis-fused delta-lactone (4aR,7aR)-hexahydro-5-iodocyclopenta[c]pyran-3(1H)-one (11), which was subsequently elaborated to hydroxylactone 1 through a stereocontrolled Pd(II)-mediated lactonization reaction. En route to preclavulone A, a putative elusive intermediate in the biosynthesis of clavulones, the synthetic utility of compound 1 was demonstrated. The key feature in this synthesis was the installation of the lower side chain via the Knochel organozinc sp3-sp C-C coupling protocol.",10.1021/jo061321h,2006-09-26,0.7073858442526701
Journal of Organic Chemistry,Rapid and Efficient Synthesis of Dysiherbaine and Analogues to Explore Structure−Activity Relationships,"A rapid and efficient total synthesis of dysiherbaine (1), a potent and subtype-selective agonist for ionotropic glutamate receptors, has been accomplished. A key intermediate 15 was synthesized by two approaches. The first synthetic route utilized compound 9, an advanced intermediate in our previous total synthesis of neodysiherbaine A, as the starting point, and the cis-oriented amino alcohol functionality on the tetrahydropyran ring was installed by using an intramolecular S(N)2 cyclization of N-Boc-protected amino alcohol 20. An alternative and even more efficient synthetic approach to 15 featured stereoselective introduction of an amino group at C8 by iodoaminocyclization prior to constructing the bicyclic ether skeleton. The amino acid appendage was efficiently constructed by a catalytic asymmetric hydrogenation of enamide ester 36. The synthetic route developed here provided access to several dysiherbaine analogues, including 9-epi-dysiherbaine (38), 9-deoxydysiherbaine (39), 9-methoxydysiherbaine (40), and N-ethyldysiherbaine (41). The preliminary structure-activity relationship studies revealed that the presence and stereochemistry of the C9 hydroxy group in dysiherbaine is important for high-affinity and selective binding to glutamate subtype receptors.",10.1021/jo702116c,2007-12-06,0.707368716104498
Journal of Organic Chemistry,Desymmetrization of a Centrosymmetric Diepoxide:  Efficient Synthesis of a Key Intermediate in a Total Synthesis of Hemibrevetoxin B,"The preparation of an established intermediate in a total synthesis of hemibrevetoxin B is described. The acid-catalyzed cyclization of trans-4,5-epoxyoctane-2,7-dione exhibited a valuable mixture of kinetic and thermodynamic control: stereospecific epoxide opening was followed by equilibration of the products to provide the required trans-fused octahydropyrano[3,2-b]pyran ring system. Two-directional elaboration, by acetal substitution, ozonolysis, and sulfur ylide-mediated epoxidation, provided a centrosymmetric diepoxide. The key step of the synthesis was the first desymmetrization of a centrosymmetric molecule in natural product synthesis: Jacobsen asymmetric epoxide hydrolysis and acetonization provided the known synthetic intermediate in 97% yield and >95% ee over two steps. The exploitation of the center of symmetry of the AB ring system of the natural product contributed greatly to the efficiency (eight steps, 34% overall yield) of the synthesis.",10.1021/jo026456b,2002-12-31,0.707358260547736
Organic Letters,Spongistatin Synthetic Studies. Evolution of a Scalable Synthesis for the EF Fragment of (+)-Spongistatin 1 Exploiting a Petasis−Ferrier Union/Rearrangement Tactic,"[structure: see text] An efficient, stereocontrolled, and scalable second-generation synthesis of (+)-3, an advanced EF subtarget for the total synthesis of (+)-spongistatin 1, has been achieved. Highlights of the strategy include preparation of the F-ring pyran via a Petasis-Ferrier union/rearrangement sequence and installation of the chlorodiene side chain employing a cyanohydrin alkylation. The longest linear sequence, 26 steps, proceeds in 8.3% overall yield.",10.1021/ol048418f,2004-09-01,0.707269495119794
Synlett,An Efficient Synthetic Routeto Homocarbonyltopsentine,"Efficient synthesis of homocarbonyltopsentine Ia, starting from readily available triiodoimidazole 9 and 3-formylindoles 2 and 18 is described. The key steps of the synthesis are selective halogen-metal exchanges at the imidazole nucleus and subsequent addition to formylated indoles.",10.1055/s-2003-40843,2003-01-01,0.707250333336378
Journal of Organic Chemistry,"A Condensed, Scalable Synthesis of Racemic Koningic Acid","The natural product koningic acid (KA) is a selective covalent inhibitor of glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a critical node in the glycolysis pathway. While KA is available commercially, sources are limited and its cost becomes rapidly prohibitive beyond the milligram scale. Additionally, a practical and flexible synthetic route to KA and analogs remains to be developed. Here we detail a new route that is operationally safer, scalable and offers a five-step reduction in the previously reported longest linear sequence.",10.1021/acs.joc.0c00344,2020-04-21,0.7072106395671033
Organic Process Research & Development,Process Development of a Novel Non-Xanthine Adenosine A<sub>1</sub> Receptor Antagonist,"(+)−( R )-1-[( E )-3-(2-phenylpyrazolo[1,5- a ]pyridin-3-yl)acryloyl]-2-piperidine ethanol (FK453) is a novel, potent adenosine A 1 receptor antagonist for the regulation of renal function. The development of a reliable process suitable for large scale manufacture is described. A Horner−Emmons reaction and a 1,3-dipolar cycloaddition were successfully scaled up to afford ethyl ( E )-3-(2-phenylpyrazolo[1,5- a ]pyridin-3-yl)acryloylate, with excellent regioselectivity and stereoselectivity. Process improvements and optimization of each step permitted elimination of column chromatography, resulting in a straightforward, practical synthesis of FK453.",10.1021/op990044w,1999-09-03,0.707178621878677
Journal of Organic Chemistry,"A Highly Efficient Synthesis of Fibrinogen Receptor Antagonist L-734,217 via a Novel Chemoselective Silyl-Mediated Conjugate Addition of δ-Lactams to 4-Vinylpyridine","A highly practical chromatography-free six-step synthesis of L-734,217 suitable for large scale preparation is described. The key chiral pyridine acid intermediate ( R )- 1 was prepared in four steps based on a novel chemoselective silyl-mediated conjugate addition of ethyl (2-oxopiperidin-1-yl)acetate to 4-vinylpyridine and a highly productive, recyclable, kinetic resolution with quinine. Subsequent salt breaking/peptide coupling with benzyl 3-( R )-aminobutyrate ( 2 ) in a biphasic system, followed by concomitant hydrogenation of the pyridine ring and debenzylation afforded L-734,217 in 20% overall yield (30% with one recyle) from 2-piperidone. The mechanism of this key conjugate addition to 4-vinylpyridine was studied by 13 C NMR.",10.1021/jo951214f,1996-01-01,0.7071698188734921
European Journal of Organic Chemistry,The Formal Total Synthesis of Epothilone A,The formal total synthesis of epothilone A is described. The key steps in the synthesis of the northern hemisphere are a Z-selective ten-membered ring-closing metathesis reaction (RCM) and the diastereoselective alkylation at C8. Aldehyde 3 is formed by introduction of the thiazole moiety by a Wittig reaction and subsequent functional group transformation. An efficient route to keto acid 5 is described.,10.1002/(sici)1099-0690(199911)1999:11<2817::aid-ejoc2817>3.3.co;2-c,1999-11-01,0.7070995372853647
European Journal of Organic Chemistry,The Formal Total Synthesis of Epothilone A,The formal total synthesis of epothilone A is described. The key steps in the synthesis of the northern hemisphere are a Z-selective ten-membered ring-closing metathesis reaction (RCM) and the diastereoselective alkylation at C8. Aldehyde 3 is formed by introduction of the thiazole moiety by a Wittig reaction and subsequent functional group transformation. An efficient route to keto acid 5 is described.,10.1002/(sici)1099-0690(199911)1999:11<2817::aid-ejoc2817>3.0.co;2-l,1999-11-01,0.7070995372853647
Organic Process Research & Development,Process Development and Scale-Up of PPAR α/γ Dual Agonist Lobeglitazone Sulfate (CKD-501),"A scaleable synthetic route to the potent PPARα/γ dual agonistic agent, lobeglitazone ( 1 ), used for the treatment of type-2 diabetes was developed. The synthetic pathway comprises an effective five-step synthesis. This process involves a consecutive synthesis of the intermediate, pyrimidinyl aminoalcohol ( 6 ), from the commercially available 4,6-dichloropyrimidine ( 3 ) without the isolation of pyrimidinyl phenoxy ether ( 4 ). Significant improvements were also made in the regioselective 1,4-reduction of the intermediate, benzylidene-2,4-thiazolidinedione ( 10 ), using Hantzsch dihydropyridine ester (HEH) with silica gel as an acid catalyst. The sulfate salt form of lobeglitazone was selected as a candidate compound for further preclinical and clinical study. More than 2 kg of lobeglitazone sulfate ( CKD-501, 2 ) was prepared in 98.5% purity after the GMP batch. Overall yield of 2 was improved to 52% from 17% of the original medicinal chemistry route.",10.1021/op060087u,2007-01-20,0.7070548249306637
Angewandte Chemie International Edition,Asymmetric Formal Synthesis of Azadirachtin,"An asymmetric formal synthesis of azadirachtin, a potent insect antifeedant, was accomplished in 30 steps to Ley's synthetic intermediate (longest linear sequence). The synthesis features: 1) rapid access to the optically active right-hand segment starting from the known 5-hydroxymethyl-2-cyclopentenone scaffold; 2) construction of the B and E rings by a key intramolecular tandem radical cyclization; 3) formation of the hemiacetal moiety in the C ring through the α-oxidation of the six-membered lactone followed by methanolysis.",10.1002/anie.201507935,2015-10-16,0.7069936849027708
Organic Process Research & Development,Practical and Scalable Synthesis of S1P<sub>1</sub> Receptor Agonist ACT-209905,"A practical and scalable route for the fast delivery of 12 kg of S1P 1 agonist (ACT-209905) has been developed. ACT-209905 is composed of an amino pyridine group, an oxadiazole spacer, a 2-ethyl-5-methylphenol moiety and a chiral 1-amino-2-propanol side chain. The convergent synthesis consists of 16 steps with 9 isolated intermediates and is chromatography-free. Key building blocks are accessed from low-cost starting materials, such as acetone, diethyl oxalate, cyanoacetamide, and 2-ethyl-5-methyl aniline. A Negishi coupling that was troubled by the use of metal reagents and concomitant metal waste streams has been replaced by a less expensive Guareschi–Thorpe reaction to build up an amino isonicotinic acid. The chiral 1-amino-2-propanol moiety was secured by selective ring-opening of an epoxide with lithium hexamethyldisilazide as an ammonia surrogate, thus omitting the notorious double alkylated byproduct.",10.1021/op200326s,2012-03-13,0.706991496747324
Synlett,"An Efficient Method for the Synthesis of a Novel Leukotriene B<sub>4</sub> Receptor Antagonist, ONO-4057, via Michael Reaction of Dihydroresorcinol","All articles of this category A practical method for the synthesis of ONO-4057, a highly potent and orally active leukotriene B 4 (LTB 4 ) receptor antagonist, was developed. This method includes improved synthesis of a key intermediate, 1,3-dioxo-2-(2-ethoxycarbonylethyl)cyclohexane ( 6 ). leukotriene B4 - antagonist - dihydroresorcinol - Michael addition",10.1055/s-1997-1079,2000-12-31,0.7068883169499228
Organic Process Research & Development,"Large-Scale Synthesis of Chiral Tetrahydropyran via Asymmetric Allylation Catalyzed by (<i>S</i>)-3,3′-Cl<sub>2</sub>-BINOL","Asymmetric synthesis of chiral tetrahydropyran 3, a key intermediate of PDE2 inhibitor 1, has been achieved in five linear steps with a 49% overall yield and >99:1 er on a large scale. The whole chemical process was realized without silica gel chromatography purification, starting from tert -butyl 2-chloro-5-(2-chloroacetyl)benzoate 7 . The key features of current synthesis include asymmetric allylation catalyzed by an organocatalyst ( S )-3,3′-Cl 2 -BINOL under solvent-free conditions.",10.1021/acs.oprd.2c00258,2022-10-03,0.7068634462882806
Synthesis,Practical Early Development Synthesis of Nav1.7 Inhibitor GDC-0310,"The concise early development route to the Nav1.7 inhibitor GDC-0310 is described. The active pharmaceutical ingredient (API) contains one stereocenter, which was obtained with high enantiomeric excess (&gt;99:1) by using an SN2 displacement approach to connect two intermediates: a chiral benzyl alcohol and a piperidine. The synthesis of the piperidine building block proceeded via a regioselective SNAr reaction on 1-chloro-2,4-difluorobenzene by N-Boc-4-piperidinemethanol, followed by installation of the methyl ester group by electrophilic aromatic bromination and a palladium-catalyzed alkoxycarbonylation. A subsequent Suzuki–Miyaura cross-coupling reaction was then telescoped directly into cleavage of the Boc group to provide the advanced piperidine intermediate. The key feature of the synthesis is the highly selective SN2 displacement of the chiral mesylate of (R)-1-(3,5-dichlorophenyl)ethan-1-ol with the piperidine intermediate, followed by a chiral purity upgrade via the corresponding (1S)-(+)-camphorsulfonic acid salt. After standard hydrolysis of the methyl ester and CDI mediated amidation to couple the resulting acid with methanesulfonamide, enantiomerically pure GDC-0310 was obtained in high overall yield (37%) on a 6.5 kilogram scale.",10.1055/s-0040-1707859,2020-06-22,0.7068252381451519
Journal of the American Chemical Society,A Concise Total Synthesis of Saliniketal B,"We report a concise, enantioselective, and highly efficient synthesis of the marine actinomycete-derived natural product saliniketal B. Our approach was motivated with an eye toward future structure-function studies of this inhibitor of phorbol ester-mediated ornithine decarboxylase induction via an unknown mechanism. Our strategy highlights the utility of Pt(II)-mediated cycloisomerization of alkynediols developed in our laboratory to construct the dioxabicyclo[3.2.1]octane ring system, a highly selective aldol fragment coupling whose stereochemical outcome is influenced by a gamma-stereogenic methyl group, and an interesting one-pot desilylation/dihydropyranone fragmentation/amidation sequence. As such, saliniketal B was obtained in 11 steps and 23% overall yield from commercially available starting material via a convergent coupling of two equally complex fragments assembled in seven and eight steps (39 and 45%), respectively.",10.1021/ja9061757,2009-08-18,0.706747685096722
Synlett,A Stereoselective Synthesis of the ACE Inhibitor Trandolapril,"A conceptually novel and stereoselective synthesis of the enantiopure octahydroindole building block and its conversion into the ACE inhibitor trandolapril was achieved. Key steps include the α-allylation of a protected l-pyroglutamic acid derivative, a highly diastereoselective Hosomi–Sakurai reaction and a Ru-catalyzed ring-closing metathesis of a 4,5-diallylated proline. This way, the synthesis of trandolapril was efficiently achieved in 25% overall yield (12 steps).",10.1055/s-0037-1612306,2019-03-15,0.706695170014105
Journal of Organic Chemistry,En Route to 2-(Cyclobuten-1-yl)-3-(trifluoromethyl)-1<i>H</i>-indole,"A six-step synthetic route from 4-chloro-2-methylaniline to 5-chloro-2-(cyclobut-1-en-1-yl)-3-(trifluoromethyl)-1H-indole (1) has been reported. Compound 1a is a key impurity of reverse transcriptase inhibitor efavirenz, an important anti-HIV/AIDS drug. Synthetic challenges, dead ends, and detours are discussed.",10.1021/acs.joc.8b00100,2018-01-30,0.7066894373447457
Organic Process Research & Development,Route Design and Scale-Up of a Topoisomerase I Inhibitor Antibody–Drug Conjugate Payload,"AstraZeneca is currently developing an antibody–drug conjugate for the treatment of cancer with a topoisomerase I inhibitor payload. The drug portion of the molecule is an analogue of the natural product camptothecin. We describe the initial scale-up of the synthesis to meet preclinical timelines, including route design work to shorten the route by five steps. We also detail several problems we encountered, most notably a low-yield final step. We developed a second-generation route to address these issues, increasing the overall yield from 3.4% to 7.8% while reducing the process mass intensity by 66%. We discuss the impurities formed throughout the process and highlight our workup and purification strategy to remove them.",10.1021/acs.oprd.4c00175,2024-06-11,0.7065993221454147
Journal of Organic Chemistry,"Practical Asymmetric Synthesis of (<i>S</i>)-MA20565, a Wide-Spectrum Agricultural Fungicide","A practical asymmetric synthesis of a wide-spectrum agricultural fungicide, (S)-MA20565 (1), is described. The convergent synthesis was achieved starting from commercially available 3-(trifluoromethyl)aniline (7) in 44% overall yield through five steps and 2-bromobenzaldehyde (9) in 48% overall yield through four steps, respectively. (S)-O-[1-(3-Trifluoromethylphenyl)ethyl]hydroxylamine (2), a key intermediate of 1, was prepared via ruthenium(II)-catalyzed asymmetric transfer hydrogenation of 1-(3-trifluoromethylphenyl)ethanone (6) followed by chlorination using methanesulfonyl chloride and oxyamination using potassium acetohydroxamate with high level of stereocontrol.",10.1021/jo991271z,1999-12-22,0.7065677355272829
Journal of Organic Chemistry,Efficient Total Synthesis of (−)-Ilimaquinone,"The total synthesis of (-)-ilimaquinone, a metabolite isolated from sea sponges, is described. The key step of the synthesis is the attachment of the quinone moiety to the drimane skeleton. Alkylation of enone 11 obtained in four steps from the readily available diketone 8, with tetramethoxybenzyl bromide 15 as the alkylating agent, led to addition product 16 in excellent yield. The presence of the tetramethoxybenzyl group induced stereoselective hydrogenation of the exo olefin 18, leading to the required isomer in a 9:1 ratio. Treatment of compound 21 with ceric ammonium nitrate (CAN) afforded formation of the quinone and deprotection of only one methyl ether in one step to furnish the desired ilimaquinone 1.",10.1021/jo9805192,1998-07-30,0.706438511852763
Organic Letters,Facile and Efficient Synthesis of Naturally Occurring Carbasugars (+)-Pericosines A and C,"An efficient synthesis of antitumor marine natural product (+)-pericosine A was achieved from (-)-quinic acid in 11.7% overall yield, which is 20 times better than our previously reported synthesis. The crucial steps of this synthesis include the regio- and stereoselective bromohydrination of an unstable diene and the ring opening of an epoxide. This synthetic route was applicable to a synthesis of (+)-pericosine C and also to a synthesis of (-)-pericosine C.",10.1021/ol9008188,2009-05-27,0.7063638767514875
Organic Process Research & Development,Transition-Metal-Free Synthesis of a Densely Functionalized Benzodioxole Intermediate toward Lotiglipron,"A decagram-scale preparation of the key intermediate (±)-2-(4-bromo-2-methylbenzo[ d ][1,3]dioxol-2-yl)-5-chloropyridine is described. Key steps involve a double nucleophilic substitution of 3-bromocatechol with methyl 2,2-dichloropropanoate, use of a Weinreb amide to facilitate the formation of a ketone from a carboxylic acid, and de novo construction of a substituted chloropyridine from a vinamidinium salt. Process developments enabled isolation of multigram quantities of final product in 34% yield after 5 steps and no chromatography.",10.1021/acs.oprd.3c00472,2024-03-12,0.7062937805119077
Synthesis,"An Improved, Practical, and Scalable Five-Step Synthesis of Psilocybin","Described herein is an improved synthesis of 3-[2-(dimethylamino)ethyl]-1H-indol-4-yl dihydrogen phosphate (psilocybin). The protocol outlines: synthesis of multigram quantities of psilocybin, identification of critical in-process parameters, and isolation of psilocybin without the use of chromatography, TLC, or aqueous workup. The synthesis furnishes psilocybin in five steps in 23% overall yield from an inexpensive acetoxyindole starting material. With specific focus on process control and impurity fate and removal, the improved procedure is amenable to providing high-quality psilocybin.",10.1055/s-0039-1691565,2020-01-08,0.7061908390902752
Organic Process Research & Development,"Process Development and Kilogram-Scale Manufacture of Key Intermediates toward Single-Enantiomer CELMoDs: Synthesis of Iberdomide·BSA, Part 1","Iberdomide ( 1 ·HCl) is a cereblon E3 ligase-modulating drug (CELMoD) in clinical trials for the treatment of systemic lupus erythematosus (SLE) and relapsed and refractory multiple myeloma (MM). The structure features an isoindolinone core as well as a chiral α-amidoglutaramide moiety. An efficient kilogram-scale synthesis of the drug substance was required to enable clinical trials and development activities. The retrosynthetic disconnections, which proceed through acid-catalyzed glutarimide formation, lead to three starting materials, the syntheses of which are discussed. A benzylic chloride was formed through morpholine alkylation of a bisbenzylic chloride and efficient selective removal of the undesired minor bisamino impurity. Duff formylation was used to prepare the salicylaldehyde building block, and the isolation of this compound was enabled by an innovative simultaneous addition of acidic and basic solutions. A short sequence to l -isoglutamine tert -butyl ester was developed to supply the chiral amine crucial to the formation of the α-amidoglutaramide.",10.1021/acs.oprd.3c00315,2023-12-28,0.706156721139513
Organic Letters,Exploiting Pseudo <i>C</i><sub>2</sub>-Symmetry for an Efficient Synthesis of the F-Ring of the Spongistatins,"A concise and efficient synthesis of the F-ring fragment of the potent antimitotic marine macrolide spongistatin 1 has been developed. The key sequence involves double cross-metathesis/Sharpless asymmetric dihydroxylation reactions to establish four stereocenters in a pseudo C2-symmetric array, followed by a selective protection reaction that breaks the pseudosymmetry, establishes a fifth stereocenter, and effectively differentiates the ester termini. Overall, the six contiguous stereocenters in the C(37)-C(45) F-ring fragment are established in just seven steps.",10.1021/ol402604s,2013-10-10,0.7060577672524945
Organic Process Research & Development,"New Efficient Asymmetric Synthesis of Taranabant, a CB1R Inverse Agonist for the Treatment of Obesity","Taranabant ( 1 ) is a cannabinoid-1 receptor (CB1R) inverse agonist that was recently in late-stage clinical development for the treatment of obesity. The previously employed synthesis exhibited a number of shortcomings for continuing development, and in this paper we report an improved synthesis of the target molecule that is suitable for large-scale implementation. Palladium-catalyzed amidation of an enol tosylate afforded a stereodefined tetrasubstituted enamide, and asymmetric hydrogenation thereof provided the target molecule.",10.1021/op800270e,2009-01-16,0.7060369482209221
European Journal of Organic Chemistry,Studies on the Total Synthesis of Lactonamycin: Synthesis of the Fused Pentacyclic B–F Ring Unit,"Abstract This paper describes an approach towards the total synthesis of lactonamycin with the elaboration of a key pentacyclic unit. Key steps include the synthesis of benzyl bromide 8 in eight steps and 23 % overall yield starting from 4‐methoxyphenol; a high‐yielding Suzuki coupling between boronic ester 9 and benzyl bromide 8 ; and a Lewis acid mediated, intramolecular Friedel–Crafts acylation to obtain the fused BCDEF ring core.",10.1002/ejoc.201101317,2011-11-15,0.7060202145707152
Organic Letters,"Stereoselective Synthesis of 2-Acetamido-1,2-dideoxyallonojirimycin (DAJNAc), a New Potent Hexosaminidase Inhibitor",A practical synthesis of the previously unreported N-acetyl-D-allosamine glycomimetic DAJNAc is described. The reaction sequence involves Pd-catalyzed allylic substitution by phthalimide in an azaheterobicyclic scaffold as the key step. The new iminosugar resulted in being a stronger β-N-acetylglucosaminidase (human placenta) competitive inhibitor than the D-gluco (DNJNAc) and D-galacto (DGJNAc) stereoisomers.,10.1021/ol401517x,2013-06-26,0.7060107400716474
Organic Process Research & Development,"Development of a Practical Synthesis of the Progesterone Receptor Antagonist 4-{[3-Cyclopropyl-1-(mesylmethyl)-5-methyl-1H-pyrazol-4-yl]oxy}-2,6-dimethylbenzonitrile","The development and implementation of a scaleable process for the manufacture of the nonsteroidal progesterone receptor antagonist 8 is described. Key aspects of the synthesis include (i) a telescoped chlorination−etherification sequence to prepare diketone 4 and (ii) separation of pyrazole regioisomers 6 and 7 through formation of their hydrogen sulfate salts and selective crystallization, followed by oxidation to 8 .",10.1021/op900110k,2009-07-08,0.7057276317604783
Organic Letters,An Efficient Synthesis of Optically Active Physostigmine from Tryptophan via Alkylative Cyclization,"[reaction: see text] A new and efficient synthetic route to physostigmine is described. Corey-Kim reagent reacted with tryptamine or tryptophan carbamates to give 3a-(methylthiomethyl)hexahydropyrrolo[2,3-b]indole skeletons. Formal total synthesis of racemic and chiral physostigmine was accomplished in excellent overall yields, in short steps.",10.1021/ol005513p,2000-02-05,0.7056774220594653
Synthesis,Confirmation of the Structure of Ventiloquinone J through Synthesis,"An unambiguous route has been developed for the synthesis of rac ventiloquinones J and E as well as their diastereoisomers, rac isoventiloquinones J and E by using a mercury(II) mediated ring closure as a key step.",10.1055/s-2004-822370,2004-05-18,0.7056569645698126
Organic Process Research & Development,Development of a Scaleable Synthesis of a Partial Nicotinic Acid Receptor Agonist,"A practical and efficient synthesis of 1,4,5,6-tetrahydro-3-(1 H -tetrazol-5-yl)cyclopenta[ c ]pyrazole, 1, is described. A new one-pot process has been developed, starting from the commercially available 1 H -tetrazole-5-carboxylic acid-ethyl ester sodium salt which is reacted in a pseudo -Claisen condensation reaction with cyclopentanone, followed by the addition of hydrazine.",10.1021/op800290t,2009-03-16,0.7056105751565667
Organic Process Research & Development,"A Facile and Scaleable Synthesis of 3-<i>O</i>-Decladinose-6-methyl-10,11-dehydrate-erythromycin-3-one-2‘-acetate, an Important Intermediate for Ketolide Synthesis","A facile and scaleable synthetic process of compound 2, an important intermediate for synthesis of ketolide semisynthetic antibiotics, was developed starting from commercially available clathromycin with an overall yield of ∼74%. This synthetic pathway was composed of four steps from compound 3 which could be prepared from clathromycin without using expensive reagents such as EDC·HCl (1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride) or more active reagents such as methanesulfonic anhydride. This new process was efficient and practical as demonstrated by scale-up to prepare more than 1 kg of pure compound 2 .",10.1021/op060001x,2006-03-22,0.7054985916344999
Organic Process Research & Development,Concise Synthesis of a Potential 5-Lipoxygenase Activating Protein (FLAP) Inhibitor and Its Analogs through Late-Stage Alkene Dicarbofunctionalization,"We report a five-step synthesis of the biologically important 1,1-diarylalkane 1, a potential 5-lipoxygenase activating protein (FLAP) inhibitor that was synthesized previously in 12 steps. In this synthesis, we apply a three-component alkene dicarbofunctionalization reaction as a key final step to assemble the potential FLAP inhibitor 1 from commercially available starting materials. In addition, we also report the synthesis of a variety of new analogs of the inhibitor 1 and its regioisomer.",10.1021/acs.oprd.9b00199,2019-06-21,0.7054427490692465
Organic Process Research & Development,Development of a Practical Large-Scale Synthesis of Denagliptin Tosylate,"A large-scale synthesis of denagliptin tosylate has been developed. The efficiency of the synthesis has been improved from the initially scaled route by changing the order of steps (performing a dehydration at a late stage). The key step of the synthesis is a single-step peptide coupling/dehydration, mediated by n -propanephosphonic acid cyclic anhydride. The challenges of developing this synthesis into a robust and practical manufacturing route are described.",10.1021/op900178d,2009-08-20,0.7053240997623762
Tetrahedron,"Asymmetric synthesis of (1R,2S)-2-fluorocyclopropylamine, the key intermediate of the new generation of quinolonecarboxylic acid, DU-6859",,10.1016/s0040-4039(00)92670-4,1992-06-01,0.7052273442073699
Organic Process Research & Development,"An Efficient Scale-Up Synthesis of BMS-520, a Potent and Selective Isoxazole-Containing S1P<sub>1</sub> Receptor Agonist","This article reports an efficient scale-up synthesis of 1-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylic acid (BMS-520), a potent and selective isoxazole-containing S1P 1 receptor agonist. This process features a highly regioselective cycloaddition leading to a key intermediate, ethyl 3-phenyl-4-(trifluoromethyl)isoxazole-5-carboxylate, a chemo-selective hydrolysis of its regioisomers, as well as an improved method for 1,2,4-oxadiazole formation, relative to the original synthesis. The improved process was applied to the preparation of multiple batches of BMS-520 for preclinical toxicological studies.",10.1021/acs.oprd.6b00112,2016-05-05,0.7052031556247015
Tetrahedron,A novel route to the tetracyclic ring of anthracyclinones,,10.1016/s0040-4039(00)92910-1,1976-05-01,0.7051425177777452
Synlett,A New and Efficient Synthesis of Substituted 2-Hydroxymethyl-2-methyl-2H-chromenes,"A new and efficient three step procedure for the synthesis of functionalized 2H-chromenes 1 is described, starting from commercially available salicylaldehydes 2 and 2-methylpropenylmagnesium chloride 3, which involves catalytic acid-mediated intramolecular cyclization of phenolic epoxide 5 as the key step.",10.1055/s-2002-19763,2002-01-01,0.7050791531176664
Tetrahedron,"A simple, efficient route to the synthesis of dibenzocoumaranones and aristolactams.",,10.1016/s0040-4039(00)61213-3,1992-08-01,0.705031509156928
Synlett,"Efficient Enantioselective Formal Synthesis of Ro 67-8867, a NMDA 2B Receptor Antagonist",An efficient enantioselective formal synthesis of Ro 67-8867 has been achieved in 7 steps using an amino-zinc-ene-enolate cyclization and an enantioselective ring enlargement of a substituted prolinol as the key steps.,10.1055/s-2005-865225,2005-01-01,0.7049712865246238
European Journal of Organic Chemistry,Preparation of Highly Alkoxy‐Substituted Naphthaldehyde Derivatives – A Regioselective Approach to Building Blocks for the Synthesis of Rubromycins,"Abstract An efficient synthesis of highly substituted naphthaldehyde derivatives 8 was required for the planned synthesis of compounds of the rubromycin family. Three different routes towards this goal were attempted. Route I started with 1,5‐dihydroxynaphthalene ( 10 ), and the pentaalkoxy‐substituted naphthaldehyde 17 was obtained in a straightforward sequence in moderate overall yield. Route II employed an aryne cycloaddition to generate the functionalized naphthalene skeleton. This sequence smoothly provided the bromonaphthalene derivative 19 , which served as a very suitable precursor of aldehyde 24 , boronic acid 25 , and finally the unsymmetrically substituted hexaalkoxynaphthalene derivative 18 . Unfortunately, though, the regioselective formylation of 18 to provide the desired aldehyde 8a was not possible, this key compound being obtained only in low yield. Whereas an attempted Claisen rearrangement of O ‐allylated derivative 30 furnished the wrong regioisomer 33 , the ortho ‐Fries rearrangement of the easily available carbamate 34 smoothly afforded the expected amide 35 , which turned out to be essentially inert and could not be converted into the corresponding naphthaldeyde 8b . We therefore developed Route III, involving an alternative aryne cycloaddition and a subsequent regioselective ring‐opening of the tricyclic adduct 41 . This sequence enabled us to efficiently prepare acetal 44 , which was transformed into the desired highly substituted and regioselectively protected naphthaldehyde derivative 8b . The synthesis of this key compound could be achieved in a 12‐step sequence in an overall yield of 9 %. Our planned rubromycin synthesis was successfully verified by the conversion of 8b into the protected α‐hydroxy enone 7b by addition of lithiated methoxyallene followed by hydrolysis and subsequent silylation of intermediate 7a . (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2006)",10.1002/ejoc.200600353,2006-08-02,0.7049471513701934
Journal of Organic Chemistry,Total Synthesis of Nhatrangin A,"A concise and stereoselective approach for the synthesis of key intermediates for aplysiatoxins, oscillatoxins, and nhatrangins and their utility for the total synthesis of nhatrangin A has been demonstrated. The advanced intermediates aromatic aldehyde 11 and dihydroxy acid 12 were synthesized in eight steps (44% overall yield) and three steps (55% overall yield), respectively. An asymmetric Michael addition, CBS reduction, and proline-catalyzed crossed-aldol reactions were utilized as key steps for the generation of all the chirality of main chain hydroxyaldehyde, while the appended side-chain-protected 3,4-dihydroxypentanoic acid was achieved in a shortest route, using Sharpless dihydroxylation, diol protection, and RuO4-catalyzed aromatic over-oxidation reactions. Synthesis of nhatrangin A was accomplished by coupling of dihydroxy acid 12 with β-hydroxyallyl ester (obtained from 11) under Yamaguchi reaction conditions followed by a one-pot deprotection of all protecting groups.",10.1021/jo401248n,2013-08-08,0.7048977310341288
Organic Process Research & Development,Improved Multigram Route to a Tricyclic Key Intermediate for Dibenzosuberone-Based p38 Inhibitors via an Optimized Early-Stage Heck Coupling,"The p38α MAP kinase has been a heavily investigated target in the last two decades. The structural class of dibenzosuberone-based p38 inhibitors, exemplified by the promising candidate skepinone-L, was already successfully validated in several in vivo models of inflammatory as well as oncologic indications. The increasing demand of key intermediates and final compounds caused by the ongoing development of this inhibitor class urged the conception of an optimized route for the preparation of the core dibenzosuberone scaffold in multigram quantities. Rerouting of the initial discovery route resulted in an almost 4-fold increase of overall yield to 46%, the elimination of chromatographic purification, and the substitution of two critical reaction steps, which hindered a feasible scale-up. The key modification was the introduction and optimization of an early-stage Heck coupling based on Buchwald precatalysts allowing consistently high yields (ca. 90%) at multigram scales with a favorably low Pd loading of 0.1 mol %. This newly developed synthetic access to the dibenzosuberone intermediate 2-chloro-7-hydroxy-10,11-dihydro-5 H -dibenzo[ a, d ][7]annulen-5-one is capable of ensuring the supply of skepinone-L and other candidates during further development.",10.1021/acs.oprd.1c00081,2021-08-04,0.7044211083707562
Organic Process Research & Development,Synthesis of Tofogliflozin as an SGLT2 Inhibitor via Construction of Dihydroisobenzofuran by Intramolecular [4 + 2] Cycloaddition,"The synthesis of tofogliflozin ( 1 ), a sodium glucose cotransporter 2 (SGLT2) inhibitor, was achieved through the key steps of intramolecular [4 + 2] cycloaddition of dienone-yne intermediate, aerobic aromatization, and anomeric equilibration, thus enabling the construction of a dihydroisobenzofuran moiety of 1 . Subsequent hydrogenolysis followed by global deprotection afforded the desired compound 1 . The divergent synthesis of the anomer of 1 ( 15 ) is also described.",10.1021/acs.oprd.8b00400,2019-02-21,0.704418714379902
Journal of Organic Chemistry,A Modular Formal Total Synthesis of (±)-Cycloclavine,"Cycloclavine is a clavine-type Ergot alkaloid noteworthy for its unique pentacyclic skeleton featuring a 3-azabicyclo[3.1.0]hexane substructure. A short convergent route to the racemic alkaloid is described which comprises only eight linear steps and requires only four chromatographic purifications. The two key building blocks can be prepared in high yield from commercially available starting materials. Two consecutive coupling reactions, namely a selective alkylation of a dienolate and a Heck reaction, are the key steps of the reaction sequence.",10.1021/acs.joc.5b02815,2016-01-26,0.704372860441688
European Journal of Organic Chemistry,The First Total Synthesis of Topsentolide B<sub>3</sub>,"Abstract The first total synthesis of the cytotoxic oxylipin Topsentolide B 3 has been accomplished in 15 steps with an overall yield of 24 %. Starting with readily available cis ‐butene diol as a synthon, the synthesis involved Marouka allylation and Sharpless hydroxylation for the construction of three asymmetric centers. The nine‐membered lactone ring was built through a selective Grubbs ring‐closing metathesis reaction. Other key steps in the synthesis are Cu I ‐mediated alkynylation and Swern oxidation reactions. This provides a unique approach to the synthesis of oxylipins and offers the advantages of brevity and relatively high overall yield.",10.1002/ejoc.201001378,2011-01-05,0.7042920583144079
Organic Letters,[C+NC+CC] Coupling-Enabled Synthesis of Influenza Neuramidase Inhibitor A-315675,An efficient synthesis of the neuramidase inhibitor A-315675 is reported. The fully functionalized pyrrolidine core of the target is assembled in one pot via an exo-selective asymmetric [C+NC+CC] coupling reaction.,10.1021/ol3002128,2012-02-17,0.7042087744369463
Organic Letters,"<i>De Novo</i> Synthetic Approach to 2,4-Diamino-2,4,6-trideoxyhexoses (DATDH): Bacterial and Rare Deoxy-Amino Sugars","A synthetic route to 2,4-diamino-2,4,6-trideoxysugar stereoisomers in 6–7 steps and 22–33% overall yield is described. A key step in this pathway is the carbonyl coupling of d - and l -threoninol or d - and l - allo -threoninol to a phthalimido-allene mediated by chiral iridium-H 8 -BINAP, which allows for installation of two new chiral centers in one, highly diastereoselective (>20:1 dr) step. This approach provides a more concise, diastereoselective, and versatile method to access these deoxy-amino sugars than is currently available.",10.1021/acs.orglett.3c03106,2023-10-20,0.7041241409894603
Tetrahedron,A synthesis of (±)-hymenin,(±)-Hymenin (1) has been synthesized by a highly efficient route involving the generation of an azafulvene intermediate and its coupling with 2-aminoimidazole.,10.1016/0040-4039(94)85051-8,1994-01-01,0.7041080167229566
Organic Process Research & Development,"A New Process for Synthesis of Apricitabine, 2-(<i>R</i>)-Hydroxymethyl-4-(<i>R</i>)-(cytosin-1′-yl)-1,3-oxathiolane, an Anti-HIV NRTI","Apricitabine is a novel inhibitor of the HIV virus reverse transcriptase polymerase which is currently in clinical development for the treatment of AIDS. A new process for the preparation of apricitabine is presented which requires only three steps from 2-( R )-benzoyloxymethyl-1,3-oxathiolane. The new process produces the cis -(2 R,4 R ) isomer in greater than 99% diastereomeric excess by preferential crystallisation of the conglomerate form of the novel 2-( R )-benzoyloxymethyl-4-( R )-( N -benzoylcytosin-1-yl)-1,3-oxathiolane intermediate without requiring chromatography. Deprotection of the intermediate in 88% yield then gives chiral apricitabine, in 30% overall yield. The new method avoids a lengthy salt formation/-break stage, does not require toluene sulphonic acid, and introduces no new byproduct to the manufacturing process.",10.1021/op2000332,2011-04-28,0.7040944269966296
Organic Letters,Synthetic Studies on Indolocarbazoles: Total Synthesis of Staurosporine Aglycon,A synthesis of staurosporine aglycon and its analogs was achieved in a 28-36% overall yield starting from 2-methylindole. The prominent key steps for the synthesis of the indolocarbazole alkaloids involved electrocyclization and nitrene insertion reactions.,10.1021/ol200094b,2011-02-22,0.7040296743759707
Synthesis,A Facile Total Synthesis of Mubritinib,"Abstract A five-step, practical, and concise total synthesis of mubritinib is described. The synthesis utilized Friedel–Crafts acylation, click reaction, reduction, and demethylation for the construction of the triazole ring system as key steps. Another important feature of this synthesis is the Bredereck oxazole synthesis. The main advantages of this process are the improved yield and decreased number of reaction steps, which paves the way for the industrial-scale synthesis of mubritinib.",10.1055/a-1351-2370,2021-01-12,0.7040054479959539
Tetrahedron,"An improved synthesis of 3-[3-(trifluoromethyl)-3H-1,2-diazirin-3-yl]aniline: A key intermediate in the synthesis of photoaffinity probes",,10.1016/j.tetlet.2017.07.031,2017-07-12,0.7038941142762806
Organic Process Research & Development,"Development of a Practical Synthesis of STA-5312, a Novel Indolizine Oxalylamide Microtubule Inhibitor","An efficient synthesis of the novel microtubule inhibitor STA-5312 (3-[(4-cyanophenyl)methyl]- N -(3-methyl-5-isothiazolyl)-α-oxo-1-indolizineacetamide) was developed. A novel DMF/Me 2 SO 4 directed regioselective synthesis of the 3-(4-cyanobenzoyl)-indolizine ( 4 ) was a critical transformation within the four-step process. Alternatively, a CuCl mediated synthesis of 3-(4-cyanobenzyl)indolizine ( 5 ) was also developed. All intermediates were obtained in high quality and were used directly for the next step without extensive purification. The drug substance itself was purified by recrystallization from a mixture of THF and water, resulting in a high purity product (HPLC >98%). The process was applied successfully in the manufacturing of kilograms of GMP API.",10.1021/op6002852,2007-02-24,0.7038701724744283
Synlett,A Facile and Practical Total Synthetic Route for Ampelopsin F and Permethylated ε-Viniferin,"Stilbene dimers (±)-ampelospin F and permethylated (±)-ε-viniferin were synthesized by a practical synthetic route with overall yields of 10% and 27% . This route involves triethylsilane-mediated reduction of the 2,3-diarylbenzofuran,, and BBr 3 -mediated one-pot demethylation and cascade intramolecular cyclization reaction.",10.1055/s-0035-1561419,2016-03-30,0.7038658326418334
Organic Letters,Total Synthesis of (−)-Brevenal: A Concise Synthetic Entry to the Pentacyclic Polyether Core,"Total synthesis of (-)-brevenal, a novel marine polycyclic ether natural product, is described. Highly efficient and scalable entries to the AB-ring exo-olefin and the DE-ring enol phosphate and a rapid construction of the C-ring by means of our Suzuki-Miyaura coupling-based strategy realized a concise synthesis of the pentacyclic skeleton of (-)-brevenal. The present synthesis is considerably more efficient than our previous synthesis (longest linear sequence: 50 steps from 2-deoxy-d-ribose).",10.1021/ol800685c,2008-04-30,0.7038126262297226
Synlett,"A Short Synthesis of the Glycine Antagonist (3<i>R</i>,4<i>R</i>)-3-Amino-1-hydroxy-4-methyl-pyrrolidin-2-one (L-687,414)","All articles of this category A new, short synthesis of the glycine antagonist 3 R ,4 R )-3-amino-1-hydroxy-4-methylpyrrolidin-2-one (L-687,414) ( 1 ) is described, which proceeds in six steps (14% overall yield), starting from commercially available ( S )-β-methyl-γ-butyrolactone ( 4 ).",10.1055/s-1992-21462,1992-01-01,0.7038114257979423
Organic Process Research & Development,"Development of a Manufacturing Process for a Key (<i>S</i>)-5-(2,2-Dimethyltetrahydro-2<i>H</i>-pyran-4-yl)-1<i>H</i>-indole Intermediate for Orforglipron. Part III. Development of a Telescoped Phase-Transfer-Catalyzed Alkylation and Cyclopropanation Process","A scalable 8-step route for a key ( S )-5-(2,2-dimethyltetrahydro-2 H -pyran-4-yl)-1 H -indole intermediate for orforglipron was developed to support clinical trials. Highlights of process development results in this contribution include the following: (1) approximately 50% reduction of a key des-carbonyl impurity in the reductive removal of the Evans auxiliary by the introduction of MgCl 2 as a chelating agent for the reduction with LiBH 4, (2) a telescoped process for PTC alkylation with chloroacetonitrile and subsequent cyclopropyl ring formation with an asymmetric cyclic sulfate avoiding the problematic isolation of the alkylation product, and (3) significantly improved isolated yield and stereoselectivity of the cyclopropyl ring formation by replacing KHMDS with LiO t -Bu as the base for the reaction. The developed process was successfully scaled up to >400 kg scale for each step to deliver a high-quality product in an overall yield of 22%, demonstrating the robustness of the optimized process.",10.1021/acs.oprd.5c00185,2025-08-05,0.7037401217735184
Synlett,Asymmetric Synthesis of (<i>S</i>)-Vigabatrin. An Approach Using Methionine as the Chiral Pool,All articles of this category An efficient methodology for the enantioselective synthesis of (S)-γ-vinyl GABA was developed. The target chiral compound was prepared starting from commercially available (R)-methionine in five steps in 27% overall yield.,10.1055/s-1993-22438,1993-01-01,0.7037292226573642
Tetrahedron,A novel stereoselective route to a fumagillin and ovalicin synthetic intermediate,,10.1016/s0040-4039(99)00912-0,1999-06-01,0.7037109495837487
Organic Letters,Total Synthesis of (±)-Distomadines A and B,"The total synthesis of distomadines A and B, two structurally unique tetracyclic quinolines, is described. The route features a three-step process to access the pyranoquinoline butenolide rings via a Suzuki cross coupling of a 5-bromo-4-methoxycarbonylmethoxyquinoline with a vinyl boronate, followed by an α-ketohydroxylation and double cyclization by intramolecular aldol condensation and lactonization. Subsequent manipulation of the side chain to introduce the guanidine fragment completed the synthesis of distomadine B, whereas the distomadine A congener resulted from decarboxylation of a late-stage intermediate.",10.1021/ol403598k,2014-02-08,0.7036963762884788
Tetrahedron,Enantiospecific synthesis of (-)-5-epi-shikimic acid and a new route to (-)-shikimic acid,,10.1016/s0040-4039(00)73536-2,1994-07-01,0.7036785111150279
Tetrahedron,"A novel total synthesis of (+)-himbacine, a potent antagonist of the muscarinic receptor of M2 subtype",,10.1016/s0040-4039(99)00473-6,1999-04-01,0.7036530884806251
Organic Process Research & Development,A Scalable Route for the Regio- and Enantioselective Preparation of a Tetrazole Prodrug: Application to the Multi-Gram-Scale Synthesis of a PCSK9 Inhibitor,"The synthesis of multigram quantities of small molecule PCSK9 inhibitor ( R, S )- 3 is described. The route features a safe, multikilogram method to prepare 5-(4-iodo-1-methyl-1 H -pyrazol-5-yl)-2 H -tetrazole ( 10 ). A three-component dynamic kinetic resolution between tetrazole 10, acetaldehyde, and isobutyric anhydride was catalyzed by a chiral DMAP catalyst to afford enantiomerically enriched hemiaminal ester ( S )- 12 on multikilogram scale. Magnesiation, transmetalation, and Negishi coupling provided access to Boc-intermediate ( R, S )- 13, which was deprotected to provide ( R, S )- 3 in multigram quantities.",10.1021/acs.oprd.7b00304,2017-11-08,0.70364448294257
Synthesis,"Improved Synthesis of 3,5-Diamino-2,4,6-trinitrotoluene","All articles of this category A three step, efficient synthesis is described that provides the title compound in 58% overall yield from orcinol (3,5-dihydroxytoluene) monohydrate.",10.1055/s-1992-26082,1992-01-01,0.7035123923098032
Journal of Organic Chemistry,Enantioselective Synthesis of a Key “A-Ring” Intermediate for the Preparation of 1α-Fluoro Vitamin D<sub>3</sub> Analogues,"1Alpha-fluoro A-ring dienol 2, a useful building block for the preparation of fluorinated vitamin D3 analogues, was synthesized in eight steps from 4-{[tert-butyldimethylsilyl]oxy}cyclohexanone. The most distinctive synthetic development to emerge from this new synthesis is an unprecedented substrate-controlled diastereoselective fluorodesilylation of an advanced dienylsilane intermediate. This is the first enantioselective route to compound 2 relying on the use of an electrophilic fluorinating reagent.",10.1021/jo060516m,2006-06-16,0.703491925578586
European Journal of Organic Chemistry,An Economical and Practical Synthesis of <i>rac</i>‐(<i>Z</i>)‐β‐Santalol: Application of a Scriabine‐Inspired Reaction to Alkenes Results in the One‐Step Preparation of a Key Intermediate,Abstract An economical and practical synthesis of rac ‐( Z )‐β‐santalol was accomplished. The key coupling step is based on a Scriabine‐inspired reaction of a dienyl diacetate substrate and an alkene. The total synthesis was achieved in five steps (longest linear sequence) in 19 % overall yield from cyclopentadiene.,10.1002/ejoc.201403219,2014-10-29,0.7034308144301497
Journal of Organic Chemistry,Diastereoselective Synthesis of Glutamate-Appended Oxolane Rings:  Synthesis of (<i>S</i>)-(+)-Lycoperdic Acid,"The stereocontrolled synthesis of the glutamate-containing natural product (S)-(+)-lycoperdic acid is described. The key transformation in the synthetic route was an efficient diastereoselective annulation of an oxolane ring onto a pyroglutamate scaffold to construct either a gamma,gamma-disubstituted glutamate-appended tetrahydrofuran or a gamma-lactone. The reaction sequence also featured an improved method for the halogenation of pyroglutamate derivatives in high yield with enhanced stereoselection.",10.1021/jo7017137,2007-11-01,0.7033824956880079
Organic Process Research & Development,Process Development and Large-Scale Synthesis of a c-Met Kinase Inhibitor,"A highly convergent synthesis of c-Met kinase inhibitor 1 has been demonstrated on a multikilogram scale using three key fragments: dihalotricyclic core 2, chiral sulfamide side chain 3, and pyrazole boronic ester 4 . The chirality in sulfamide side chain 3 was installed using the cheap and readily available starting material ( S )-epichlorohydrin. A total of 2.71 kg of 1 were isolated in seven steps (the longest linear sequence).",10.1021/op100101q,2010-06-02,0.7033757680686423
Tetrahedron,Biomimetic route to the strobane skeleton from methyl pimarate,,10.1016/s0040-4039(00)99508-x,1989-01-01,0.7032668374370373
Organic Letters,Unusual Pyrimidine Participation: Efficient Stereoselective Synthesis of Potent Dual Orexin Receptor Antagonist MK-6096,"An asymmetric synthesis of dual orexin receptor antagonist MK-6096 (1) is described. Key steps for the trans-2,5-disubstituted piperidinyl ether fragment include a biocatalytic transamination, a trans-selective Mukaiyama aldol, and a regioselective pyridyl SNAr process. The pyrimidyl benzoic acid was synthesized via a Negishi coupling and a nitrile hydrolysis. Coupling of the two fragments via a catalytic T3P-mediated amidation completed the synthesis. Unusual behaviors in the hydrolysis of pyrimidyl benzonitrile and the amide coupling of the pyrimidyl benzoic acid are also described.",10.1021/ol5028249,2014-11-03,0.7031306718472049
Synlett,Scalable Synthesis of Amaryllidaceae Isocarbostyril Alkaloids from Enantiomerically Pure 7-Azabicyclo[2.2.1]heptanone Scaffold: Total Synthesis of (+)-7-Deoxypancratistatin,"A conceptually new and scalable strategy (ten linear steps, 13.9% overall yield) has been developed to synthesize (+)-7-deoxy­pancratistatin from optically pure 7-azabicyclo[2.2.1]heptanone scaffold. The crucial trans-B–C ring junction was fixed at an early stage of the synthesis by exploiting the rigid bicyclic structural framework of the starting precursor. Stereoselective installation of hydroxyl groups around the perimeter of the cyclohexenyl C-ring involved sequential epoxidation–phenylselenylation–oxydeselenylation sequence followed by dihydroxylation. The most attractive feature of this synthesis is the use of a protection–deprotection step only at the penultimate step making the protocol very efficient and atom economical.",10.1055/s-0036-1591022,2018-01-15,0.7031004478820811
Organic Process Research & Development,Improved and High Yield Synthesis of the Potent Arginase Inhibitor:  2(<i>S</i>)-Amino-6-boronohexanoic Acid,"A simple three-step synthesis of the potent arginase inhibitor 2( S )-amino-6-boronohexanoic acid (ABH) has been developed. The key step was alkylation of the Ni II complex of the Schiff base derived from glycine and ( S )-2-[ N ‘-( N -benzylprolyl)amino]benzophenone (BPB) with pinacol 4-bromobutylboronate. Acidic hydrolysis afforded ABH in 50% overall yield, high enantiomeric excess, and quantitative recovery of the chiral auxiliary.",10.1021/op050096n,2005-09-01,0.7029922882569121
Organic Letters,"Total Synthesis of Thapsigargin, a Potent SERCA Pump Inhibitor","The enantioselective total synthesis of thapsigargin, a potent, selective inhibitor of the Ca2+ pump SERCA, is described. Starting from ketoalcohol 8, key steps involve regioselective introduction of the internal olefin at C4-C5, judicious protecting group choice to allow chelation-controlled reduction at C3, and chemoselective introduction of the angelate ester function at C3-O. A selective esterification approach completes the total synthesis in a total of 42 steps and 0.61% overall yield (88.6% average yield per step). [reaction: see text].",10.1021/ol062947x,2007-01-27,0.7029908568097266
Journal of the American Chemical Society,Total Synthesis of Mycalamide A,"This communication describes a concise and efficient total synthesis of mycalamide A by the convergent coupling of pederic acid unit with the mycalamine unit. The left-half, (+)-7-benzoylpederic acid, was synthesized from (2R,3R)-3-methylpent-4-en-2-ol in seven steps and 34.6% overall yield through a route that features a one-step Pd(II)-catalyzed tandem Wacker/Heck cyclization reaction to prepare the tetrahydropyran ring system. The right-half, the mycalamine unit, was synthesized in 21 steps and 10.5% overall yield from diethyl d-tartrate. Effective, stereoselective methods were developed for the assembly of the two parts to yield either mycalamide A or C(10)-epi-mycalamide A.",10.1021/ja050728l,2005-05-04,0.7029747608569916
Organic Letters,A Concise and Efficient Synthesis of (−)-Allosamizoline,"A regio- and stereocontrolled total synthesis of (-)-allosamizoline is described. The key steps for this synthesis are ring-closing metathesis to form the cyclopentene core, halocyclization to afford the oxazoline ring, and finally stereoselective alkene radical addition followed by an alkene isomerization reaction to install the hydroxymethyl group. (-)-Allosamizoline was prepared in a total of 13 steps and 22% overall yield.",10.1021/ol702449m,2007-11-16,0.7029500715294471
Organic Process Research & Development,"Stereocontrolled Synthesis of Delgocitinib, a JAK Inhibitor for the Treatment of Atopic Dermatitis","Herein is reported the nine-step commercial synthesis of delgocitinib, a Janus kinase inhibitor approved for the treatment of atopic dermatitis in 2020. Its chiral spirodiamine core was selectively constructed by an intramolecular S N 2 reaction of the suitably designed γ-lactone substrate and a few subsequent steps including a selective γ-lactone ring-opening reaction with potassium phthalimide, hydrazine-free mild dephthaloylation, and one-pot reduction of β- and γ-lactams. The route affords chemically and stereochemically pure delgocitinib in 39% yield.",10.1021/acs.oprd.1c00031,2021-02-09,0.7027376116568325
Organic Process Research & Development,"A Practical Asymmetric Synthesis of Isopropyl (1<i>R</i>,2<i>S</i>)-Dehydrocoronamate","A novel asymmetric synthesis of isopropyl (1 R,2 S )-dehydrocoronamate is described from ( S )-1,2,4-butanetriol as the starting material in 28% overall yield. Highlights of this synthetic route include selective cyclopropanation between chiral cyclic sulfate 5 and diisopropyl malonate ( 8c ), formation of vinylcyclopropane 3c via elimination of halide 4c, selective monohydrolysis of diisopropyl ester 3c, and Curtius rearrangement of acid 10 to form isopropyl (1 R,2 S )-dehydrocoronamate TsOH salt 13 in >99% ee. With the involvement of only three isolations, this chromatography-free process provides a rapid and practical access to (1 R,2 S )-1-amino-2-vinylcyclopropane-1-carboxylic acid derivatives.",10.1021/op200038y,2011-03-14,0.7027202788899666
Journal of Organic Chemistry,"Asymmetric Synthesis of Tetrahydropalmatine via Tandem 1,2-Addition/Cyclization","[Reaction: see text]. The enantioselective synthesis of both enantiomers of tetrahydropalmatine (2) (ee = 98%), a natural alkaloid belonging to the tetrahydroprotoberberine family, is described. The key step of this total synthesis is based on our tandem 1,2-addition/ring-closure methodology employing lithiated methylbenzamide and benzaldehyde SAMP or RAMP hydrazones as substrates. An initial route was investigated for the formation of N- and 3-substituted dihydroisoquinolones starting from 2-substituted benzaldehyde SAMP hydrazones, but although high diastereoselectivity was achieved, only disappointing yields were obtained. In our subsequent synthetic strategy, 2,3-dimethoxy-6-methylbenzamide 6 and 3,4-dimethoxybenzaldehyde SAMP or RAMP hydrazone 19 gave the dihydroisoquinolones 20 in high diastereomeric purity (de > or = 96%) and reasonable yield (54-55%), taking into account the complex functionalities established in one step. Cleavage of the N-N bond of the chiral auxiliary and reduction of the carbonyl group of the amide moiety were performed in the same step, and the resulting tetrahydroisoquinolines 22 (ee = 99%) were N-functionalized by treatment with various electrophiles to investigate the ring closure by Pummerer, Friedel-Crafts, and Pomeranz-Fritsch reactions. The Pummerer cyclization led to the formation of (S)-(-)-2 with slight racemization (ee = 89%), whereas the Friedel-Crafts reaction proved to be unsuccessful. Finally, Pomeranz-Fritsch-type cyclization afforded the desired title compound (R)-(+)-2 in excellent enantioselectivity in 9% overall yield over seven steps and after optimization of the last step (S)-(-)-2 in 17% overall yield.",10.1021/jo051554t,2005-10-14,0.7025851664200821
Angewandte Chemie International Edition,Total Synthesis of (±)‐Corymine,"Abstract The first total synthesis of the hexacyclic indole alkaloid (±)‐corymine is described. Starting from the readily available N‐protected tryptamine, the title compound was achieved in 21 steps in 3.4 % overall yield. Key steps of the synthesis include: a) the addition of a malonate to a 3‐bromooxindole to afford 3,3‐disubstituted oxindole, b) the formation of a 12‐membered cyclic enol ether by intramolecular O‐propargylation, immediately followed by propargyl Claisen rearrangement to provide the α‐allenyl ketone stereospecifically, c) DMDO oxidation to install a hydroxy group in a highly stereoselective manner, and d) the SmI 2 ‐mediated reductive C−O bond cleavage to remove the α‐keto carboxyl group.",10.1002/anie.201704086,2017-05-03,0.7025013313112327
Journal of Organic Chemistry,Stereoselective Synthesis of Uridine-Derived Nucleosyl Amino Acids,"Novel hybrid structures of 5'-deoxyuridine and glycine were conceived and synthesized. Such nucleosyl amino acids (NAAs) represent simplified analogues of the core structure of muraymycin nucleoside antibiotics, making them useful synthetic building blocks for structure-activity relationship (SAR) studies. The key step of the developed synthetic route was the efficient and highly diastereoselective asymmetric hydrogenation of didehydro amino acid precursors toward protected NAAs. It was anticipated that the synthesis of unprotected muraymycin derivatives via this route would require a suitable intermediate protecting group at the N-3 of the uracil base. After initial attempts using PMB- and BOM-N-3 protection, both of which resulted in problematic deprotection steps, an N-3 protecting group-free route was envisaged. In spite of the pronounced acidity of the uracil-3-NH, this route worked equally efficient and with identical stereoselectivities as the initial strategies involving N-3 protection. The obtained NAA building blocks were employed for the synthesis of truncated 5'-deoxymuraymycin analogues.",10.1021/jo201935w,2011-11-07,0.7023952831225383
Journal of Organic Chemistry,Development of a Scalable Synthesis of Tofogliflozin,"An efficient and scalable synthesis of an antidiabetic drug, tofogliflozin (1), which was identified as a highly selective sodium glucose cotransporter 2 (SGLT2) inhibitor, is described. A key factor in the synthesis of 1 was the selection of the purpose-designed protecting group, which plays a strategic role in protection, chemoselective activation, and crystalline purification. The developed and optimized method made it possible to prepare 1 on a multidecagram scale without any column chromatography.",10.1021/acs.joc.5b02734,2016-02-12,0.7023808075182587
Synthesis,"Synthesis of 3′-(5-Amino-1,2,3,4-tetrazol-1-yl)-3′-deoxythymidines","All articles of this category A one-pot synthesis of the new 3′-(5-amino-1,2,3,4-tetrazol-1-yl)-3′-deoxythymidines from 3′-Azido-3′-deoxythymidine (AZT) is described. The key step is the 1,3-dipolar cycloaddition of hydrazoic acid to intermediate carbodiimides.",10.1055/s-1992-26107,1992-01-01,0.7023534101009041
Journal of Organic Chemistry,Efficient Enantiomeric Synthesis of Pyrrolidine and Piperidine Alkaloids from Tobacco,"An enantiomeric synthesis of six piperidine and pyrrolidine alkaloids, (S)-nornicotine 1, (S)-nicotine 2, (S)-anatabine 3, (S)-N-methylanatabine 4, (S)-anabasine 5, and (S)-N-methylanabasine 6, known as natural products in tobacco, was established from a common chiral homoallylic (S)-3-(1-azido-but-3-enyl)-pyridine 15. An intramolecular hydroboration-cycloalkylation of the homoallylic azide intermediate 15 served as the key step in the pyrrolidine ring formation. A ring closing metathesis reaction (RCM) of a diethylenic amine intermediate (S)-allyl-(1-pyridin-3-yl-but-3-enyl)-carbamic acid benzyl ester 20 served as the key step in the piperidine ring formation. From the commercially available 3-pyridinecarboxaldehyde 13, a short and convenient enantiomeric synthesis of tobacco alkaloids is described: (S)-nornicotine 1 (5 steps, with an overall yield of 70%), (S)-nicotine 2 (6 steps, 65%), (S)-anatabine 3 (8 steps, 30%), (S)-N-methylanatabine 4 (8 steps, 25%), (S)-anabasine 5 (8 steps, 35%), and (S)-N-methylanabasine 6 (8 steps, 25%).",10.1021/jo010386b,2001-08-23,0.7023525590838461
Organic Process Research & Development,"Catalytic, Enantioselective Synthesis of Taranabant, a Novel, Acyclic Cannabinoid-1 Receptor Inverse Agonist for the Treatment of Obesity","Chiral amide 1 (MK-0364, taranabant) is a potent, selective, and orally bioavailable cannabinoid-1 receptor (CB-1R) inverse agonist indicated for the treatment of obesity. An asymmetric synthesis featuring a dynamic kinetic resolution via hydrogenation for the preparation of the bromo alcohol 5 is disclosed. Conversion of the alcohol intermediate to the chiral amide 1 is accomplished in good overall yield.",10.1021/op700026n,2007-04-13,0.7023174679358756
Synthesis,Stereoselective Total Synthesis of Tarchonanthuslactone and Formal Synthesis of (-)-Colletol,"A simple and efficient stereoselective total synthesis of tarchonanthuslactone and formal synthesis of (-)-colletol is described using as the key steps Jacobsen's kinetic resolution and a Sharpless asymmetric epoxidation. The synthesis of tarchonanthuslactone and the seco acid proceeded in 14% and 13% overall yield, respectively, starting from chiral (R)-propylene oxide.",10.1055/s-2007-990850,2007-11-26,0.7022791924261285
Synthesis,"Scalable, Stereocontrolled, Total Synthesis of Carolacton","Abstract A route for the scalable, stereocontrolled, total synthesis of carolacton is presented starting from commercially available S-Roche ester, d-ribose, and a known allylic alcohol. Key transformations in the total synthesis include a [3,3]-Claisen rearrangement, Sharpless asymmetric epoxidation–methyl ring-opening, or Leighton asymmetric crotylation, Evans aldol–reductive deoxygenation, and ring closing metathesis (RCM). The total synthesis of carolacton (151 mg isolated, 9.2% overall yield) was completed in 23 linear steps. Additionally, 56 mg of the carolacton C15–C16 cis-olefin isomer was obtained.",10.1055/a-2105-2774,2023-06-02,0.702270489344597
Organic Process Research & Development,"Development of a Stereoselective and Scalable Synthesis for the Potent Indoleamine 2,3-Dioxygenase 1 (IDO1) Inhibitor, BMT-297376; <i>N</i>-((<i>R</i>)-1-((<i>cis</i>)-4-(3-(Difluoromethyl)-2-methoxypyridin-4-yl)cyclohexyl)propyl)-6-methoxynicotinamide","The current work describes a stereoselective and scalable route to N -(( R )-1-(( cis )-4-(3-(difluoromethyl)-2-methoxypyridin-4-yl)cyclohexyl)propyl)-6-methoxynicotinamide ( 1 ) from readily available 1,4-dioxaspiro[4.5]decan-8-one. The developed process encompasses an efficient 1,4-trans-selective synthesis of ( trans )-4-(3-(difluoromethyl)-2-methoxypyridin-4-yl)cyclohexyl methanesulfonate as the key intermediate and the use of Ellman sulfinamine methodology to install an alkyl amine in a stereoselective manner. Various synthetic routes were screened to accomplish a stereoselective and scalable protocol to access the title compound ( 1 ). This advancement enabled a competent route to the title compound in an enantioselective, safe, cost-effective, and scalable manner.",10.1021/acs.oprd.1c00142,2021-06-29,0.7022452960364853
Tetrahedron,Concise route to the key intermediate for divergent synthesis of C7-substituted fluoroquinolone derivatives,,10.1016/j.tetlet.2009.11.077,2009-11-21,0.702202589899261
Synlett,Efficient Total Synthesis of Khafrefungin: Convergent Approach Using Suzuki Coupling under Thallium-free Conditions Toward Multigram-scale Synthesis,"An efficient and practical synthetic route to khafrefungin, an antifungal agent, has been developed based on successive coupling of three components, 3, 4, and then 2. A key step of the synthesis is the Suzuki coupling of 2 and 10, in which the use of toxic thallium ethoxide has been avoided, and the coupling adduct (11) was obtained in multigram-scale quantities.",10.1055/s-2002-22726,2002-01-01,0.7021704107018808
Tetrahedron,"A novel synthetic route to phenyl-substituted pyridines synthesis of [1]benzopyrano[4,3- ]pyridines [1]benzothiopyrano[4,3- ]pyridines and pyrido[3,2- ] [1,4]benzothiazines(1-azaphenothiazines).",,10.1016/s0040-4039(00)82859-2,1988-01-01,0.7019849872312912
Tetrahedron,"A novel synthetic route to phenyl-substituted pyridines synthesis of [1] benzopyrano[4,3-b]pyridines, [1]benzothiopyrano[4,3-b]bpyridines and pyrido[3,2-b][1,4]benzothiazines(1-azaphenothiazines)",,10.1016/0040-4039(88)85265-1,1988-01-01,0.7019849872312912
Angewandte Chemie International Edition,"Enantioselective, Protecting‐Group‐Free Total Synthesis of Sarpagine Alkaloids—A Generalized Approach","A generalized synthetic access to sarpagine alkaloids through a joint synthetic sequence has been accomplished. Its applicability is showcased by the enantioselective total syntheses of vellosimine (1), N-methylvellosimine (3), and 10-methoxyvellosimine (8). The synthetic sequence is concise (eight steps) from known compound 13, and requires no protecting groups. The indole heterocycle was introduced in the last step. This strategy allows access to sarpagine alkaloids through a shared synthetic route leading to precursor 10, which we term ""privileged intermediate"". Starting from this intermediate, all sarpagine alkaloids can be synthesized using phenylhydrazines with different substitution patterns (15-17). Our approach brings about the advantage, that synthesis optimization only needs to be performed once for many natural products. The key features of the synthesis are a [5+2]-cycloaddition and a ring enlargement.",10.1002/anie.201407280,2014-10-24,0.7019746771125764
Synlett,Studies towards the Total Asymmetric Synthesis of the Pentacyclic Indole Alkaloid Arboflorine: Asymmetric Synthesis of a Key Intermediate,"The synthesis of a plausible key intermediate for a biomimetic asymmetric synthesis of indole alkaloid arboflorine is described. The method featured the use of Ellman's sulfinamide chemistry for the establishment of the first chiral center, and the Polonovski-Potier reaction for the formation of the α-aminonitrile moiety.",10.1055/s-0030-1259521,2011-01-27,0.7019656732767208
Organic Process Research & Development,Improved Synthesis of the C16–C20 Segment of Resolvin E1 Using Enantioselective Ketone Reduction and Lipase-Catalyzed Resolution,A practical synthesis targeting the C16–C20 segment of the endogenous metabolite Resolvin E1 (RvE1) is described. The original route was revised to avoid the use of source-constrained raw materials and chemistries that were problematic on larger scale. The revised route utilizes commercially available ( E )-1-chloropent-1-en-3-one as the key raw material to replace ( S )-glycidol. The ( E )-vinyl iodide functionality was installed by an addition/elimination sequence to prepare the segment required for a subsequent Sonogashira coupling. The chiral secondary hydroxyl group at C18 was established by Corey–Bakshi–Shibata (CBS) reduction followed by lipase-catalyzed acetylation to achieve chiral purity in excess of 98% ee. The revised route offered a viable multikilogram process to support early clinical production of this pro-resolution therapeutic agent.,10.1021/op4000384,2013-04-25,0.7019479963713425
Organic Letters,Asymmetric Total Synthesis of Eburnamine and Eucophylline: A Biomimetic Attempt for the Total Synthesis of Leucophyllidine,"The first enantiospecific total synthesis of (+)-6 has been achieved employing a Friedländer quinoline synthesis as a key step. Asymmetric synthesis of the architecturally complex eburnamine 5 has also been accomplished utilizing an intramolecular acid-mediated cyclization of a carbinol amine lactone moiety. Highlights of the effective modular synthetic strategy include development of the common precursor 4 for the construction of the privileged scaffolds 5 and 6 with an all-carbon quaternary stereocenter utilizing a Johnson-Claisen rearrangement strategy. Attempts have been made to synthesize 1 by the biomimetic coupling of 5 and (+)-6; however, regioisomeric 26 was formed.",10.1021/acs.orglett.7b01410,2017-06-01,0.7019278863898609
Synlett,Bioinspired Formal Synthesis of Pancracine via Selective Hydrogenation of an Indole Derivative,"Abstract A bioinspired formal synthesis of the montanine-type Amaryllidaceae alkaloid pancracine through selective hydrogenation of a 3-arylindole derivative is disclosed. The key features of this synthesis include a hexahydroindole synthesis by a chemoselective hydrogenation of an aryl-substituted indole and a diastereoselective silyl hydride reduction of an iminium intermediate generated from an enaminone through Tf2O activation. The eight-step assembly of the 5,11-methanomorphanthridine framework represents a novel and efficient strategy that permits one of the shortest syntheses of pancracine reported so far.",10.1055/a-2021-7944,2023-01-28,0.7019169635192722
Angewandte Chemie International Edition,Short Synthesis of (+)‐Actinobolin: Simple Entry to Complex Small‐Molecule Inhibitors of Protein Synthesis,"We report a concise synthesis of the naturally occurring protein synthesis inhibitor (+)-actinobolin (1). The densely functionalized and stereochemically complex molecular structure of 1 was assembled from (-)-quinic acid, L-threonine, and L-alanine as the principal components. Our route is based around a convergent strategy that features conjugate addition of an α-amino radical in the key fragment-coupling step. The dramatically simplified synthesis of (+)-actinobolin proceeding in 9 steps with 18 % overall yield has practical implications for analog preparation, as demonstrated herein.",10.1002/anie.202116520,2022-02-15,0.7018032899489519
Journal of Organic Chemistry,"Divergent Syntheses of Carbazole Alkaloids Clausenapin, Indizoline, Claulansine M, and Clausenaline D","We described the first total syntheses of clausenapin, indizoline, claulansine M, and a novel synthetic route to clausenaline D via divergent method. Key steps involved TFAA-mediated intramolecular acylation to construct the carbazole core and subsequent Claisen rearrangement to generate key intermediates for further elaboration to target molecules.",10.1021/acs.joc.6b00729,2016-04-29,0.7016768366374383
Organic Letters,Two Concise Total Syntheses of (−)-Bitungolide F,"The enantioselective total synthesis of the dual-specificity phosphatase inhibitor (-)-bitungolide F has been achieved using two convergent routes. Both strategies feature an asymmetric boron-mediated pentenylation, a stereoselective aldol, and a hydroxyl-directed 1,3-anti-reduction in order to control the stereogenic centers at C4, C5, C9, and C11. Whereas the first total synthesis was achieved in 11 steps and 14.6% overall yield using an Evans-type asymmetric alkylation, the second was completed in 9 steps and 11.4% overall yield using a highly enantioselective organocatalytic Michael addition as a key step and a protecting group free strategy.",10.1021/ol101659y,2010-08-20,0.7016131736283426
Tetrahedron,"Efficient and stereoselective synthesis of J-104,118, a novel, potent inhibitor of squalene synthase",,10.1016/0040-4039(95)01542-6,1995-10-01,0.7015848981195733
Journal of Organic Chemistry,Synthesis of quinone pyrano-.gamma.-lactone antibiotics. 1. Synthesis of 9-deoxykalafungin,"An efficient synthesis of 9-deoxykalafungin (lb) in six steps from readily available starting materials is described. The key step, in which all of the carbon atoms present in the target molecule are assembled, is the addition of 2-tert-butoxyfuran to 2-acetyl-l,4-naphthoquinone. Hydride reduction, followed by removal of the tert-butyl protecting group and addition of the C-1 alcohol to the unmasked hutenolide, affords intermediate 13, which can be oxidized with argentic oxide to lb in 17% overall yield.",10.1021/jo00420a004,1978-12-01,0.7015364725909193
Organic Process Research & Development,Multkilogram Scale-Up of a Reductive Alkylation Route to a Novel PARP Inhibitor,"Novel PARP inhibitor 1 is a promising new candidate for treatment of breast and ovarian cancer. A modified synthetic route to 1 has been developed and demonstrated on 7 kg scale. In order to scale up the synthesis to multikilogram scale, several synthetic challenges needed to be overcome. The key issues included significant thermal hazards present in a Leimgruber–Batcho indole synthesis, a low-yielding side-chain installation, a nonrobust Suzuki coupling and hydrogen cyanide generation during a reductive amination. In addition to these issues, changing from intravenous to oral delivery required a new salt form and therefore a new crystallization procedure. This contribution describes development work to solve these issues and scaling up of the new process in the pilot plant.",10.1021/op200238p,2012-11-14,0.7015171394539413
Organic Process Research & Development,A Practical Enantioselective Synthesis of a Novel Peptide Deformylase Inhibitor,"A practical synthesis of the peptide deformylase inhibitor LBM415, (2 S )- N -(5-fluoro-1-oxido-2-pyridinyl)-1-[(2 R )-2-[(formylhydroxyamino)methyl]-1-oxohexyl]-2-pyrrolidinecarboxamide, magnesium salt 11, is described. The key chiral intermediate, (2 S )- N -(5-fluoro-2-pyridinyl)-1-[(2 R )-2-[[formyl(phenylmethoxy)amino]methyl]-1-oxohexyl]-2-pyrrolidinecarboxamide 8, was made by coupling the corresponding amino acid 7 with the carboxamide 25 prepared from l -proline and 2-amino-5-fluoropyridine. Following oxidation of the pyridine nitrogen, selective hydrogenolysis of the benzyl group afforded the free acid of the drug substance, which was converted to the magnesium salt in situ with magnesium chloride. The product was obtained in an overall yield of 16% with an ee > 99%.",10.1021/op050165y,2005-12-16,0.7014382077068763
Tetrahedron,A new route to the phospholane ring-system,,10.1016/s0040-4039(01)94277-7,1972-01-01,0.7014249694027305
Tetrahedron,A new route to ring c-benzenoid steroids,,10.1016/s0040-4039(01)99914-9,1966-01-01,0.7014249694027305
Organic Process Research & Development,First- and Second-Generation Practical Syntheses of Chroman-4-one Derivative: A Key Intermediate for the Preparation of SERT/5-HT<sub>1A</sub> Dual Inhibitors,"Two approaches to large-scale synthesis of the key intermediate 9, a precursor of novel dual inhibitors of SERT/5-HT 1A receptor, are described. These two approaches each feature a mild and efficient method for construction of the chroman-4-one scaffold, which can be used with substrates containing base-sensitive functionalities and enable synthesis on kilogram scale without chromatographic purification. The first-generation synthesis enables quick delivery of a kilogram quantity of the key intermediate 9 with only one slurry purification step. On the other hand, the highly practical second-generation synthesis is suitable for the multikilogram campaign.",10.1021/op200357h,2012-02-22,0.7013500041760038
Organic Process Research & Development,Stereocontrolled First Generation Synthesis of RIPK1 Inhibitor GDC-8264,"We report an efficient, stereocontrolled, and chromatography-free first-generation manufacturing process for GDC-8264 ( 1 ), a RIPK1 inhibitor. Key steps include a diastereoselective reductive amination, a triazole condensation, an alcohol deoxyfluorination, and a late-stage Weinreb ketone formation. The 12-step process successfully produced >3.5 kg of GDC-8264 ( 1 ) in 19% overall yield with 99.2 A % HPLC purity, >99% ee, and >99.9:0.1 dr to support early stage clinical studies.",10.1021/acs.oprd.5c00125,2025-06-20,0.7013306010725427
Organic Letters,Total Synthesis of Irciniastatin A (Psymberin),The total synthesis of (+)-iriciniastatin A (psymberin) is reported in 19 steps and 6% overall yield. Key reactions include a highly convergent enolsilane-oxocarbenium ion union to generate the C8-C25 fragment and a late-stage coupling of a hemiaminal and acid chloride to complete the synthesis.,10.1021/ol901655e,2009-08-11,0.7012859696355643
Tetrahedron,An aziridine route to chiral β-lactams a novel entry to (+)-thienamycin,,10.1016/s0040-4039(00)95328-0,1987-01-01,0.7010868841225685
Organic Process Research & Development,Efficient Kilogram-Scale Synthesis of a Novel Oxazolidinone Antibacterial Candidate <b>YG-056SP</b>,"The development of an improved kilogram-scale synthesis of a novel oxazolidinone antibacterial candidate YG-056SP for the treatment of multidrug-resistant Gram-positive bacterial infection is described. The new process is highlighted by a step economical construction of the chiral N -methyloxazolidone, employing an asymmetric reduction of the carbonyl and methylamine substitution, followed by the cyclization with N, N ′-carbonyldiimidazole. Another highlight is the safe construction of the fused ring with high optical purity. Epoxy intermediates were obtained by intramolecular ring closure, and reacted with phenol fragments, followed by reduction, protection, and an intramolecular tandem reaction to afford the fused ring. The endgame process features the completion of the Miyaura reaction and the Suzuki coupling reaction in one pot and tert -butyldimethylsilyl deprotection to make dibenzyl phosphate. Finally, cheap hydrochloric acid was used to deprotect the benzyl group, which delivered YG-056SP with a defined particle-size distribution suitable for preclinical studies after crystal transformation. Compared with the initial synthetic route, the overall yield of this optimized process increased significantly from 2.3 to 29.6%.",10.1021/acs.oprd.2c00350,2023-01-20,0.7010718785337531
Journal of Organic Chemistry,Development of an Enantioselective Synthesis of (−)-Euonyminol,"We detail the development of the first enantioselective synthetic route to euonyminol ( 1 ), the most heavily oxidized member of the dihydro-β-agarofuran sesquiterpenes and the nucleus of the macrocyclic alkaloids known as the cathedulins. Key steps in the synthetic sequence include a novel, formal oxyalkylation reaction of an allylic alcohol by [3 + 2] cycloaddition; a tandem lactonization–epoxide opening reaction to form the trans -C2–C3 vicinal diol residue; and a late-stage diastereoselective trimethylaluminum-mediated α-ketol rearrangement. We report an improved synthesis of the advanced unsaturated ketone intermediate 64 by means of a 6- endo -dig radical cyclization of the enyne 42 . This strategy nearly doubled the yield through the intermediate steps in the synthesis and avoided a problematic inversion of stereochemistry required in the first-generation approach. Computational studies suggest that the mechanism of this transformation proceeds via a direct 6- endo -trig cyclization, although a competing 5- exo -trig cyclization, followed by a rearrangement, is also energetically viable. We also detail the challenges associated with manipulating the oxidation state of late-stage intermediates, which may inform efforts to access other derivatives such as 9- epi -euonyminol or 8- epi -euonyminol. Our successful synthetic strategy provides a foundation to synthesize the more complex cathedulins.",10.1021/acs.joc.1c02167,2021-11-16,0.7010456629820361
Organic Process Research & Development,The Development and Scale-Up of an Antibody Drug Conjugate Tubulysin Payload,"Significant development and scale-up work was completed on the synthesis of an antibody drug conjugate payload based on the tubulysin natural products. This work included the development of new routes to the tubuvaline and tubuphenylaniline portions of the molecules, as well as extensive optimization of the solid phase peptide synthesis used to assemble the molecule. The initial route (21 steps longest linear sequence, 0.01% overall yield) was improved to a new, more robust route (19 steps longest linear sequence, 2.4% overall yield) affording a 240-fold increase in overall yield and allowing delivery of over 86 g of the required molecule.",10.1021/acs.oprd.7b00232,2017-08-01,0.7009904479111814
Tetrahedron,"An improved synthesis of 1,1-dimethylethyl 6-cyanomethyl-2,2-dimethyl-1,3-dioxane-4-acetate, a key intermediate for atorvastatin synthesis",,10.1016/s0040-4039(02)00175-2,2002-03-01,0.7009259669550244
Organic Process Research & Development,Efficient and Practical Synthesis of Electron Transport Material and Its Key Intermediate,"An efficient and practical synthesis of 2,7-bis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)triphenylene 4 from two cheap commodity chemicals in five steps with a total yield of 48.6% was developed. This process had been successfully applied in the synthesis of electron transport material (ETM) BPyTP-2 in the gram scale with a total yield of 47.2%. This practical development of the key intermediate 4 opens a door in its further application in the synthesis of other triphenylene-based ETMs and host materials in the materials field.",10.1021/acs.oprd.7b00280,2017-09-15,0.7008655542135397
Organic Letters,"A New, More Efficient, and Effective Process for the Synthesis of a Key Pentacyclic Intermediate for Production of Ecteinascidin and Phthalascidin Antitumor Agents","An efficient process is described for the synthesis of 5, a key intermediate for the synthesis of the potent antitumor agents ecteinascidin 743 (1) and phthalascidin (2) from the readily available building blocks 3b and 4.",10.1021/ol0056729,2000-03-15,0.7008549335297767
Journal of Organic Chemistry,Enantiospecific Synthesis of Carbapentostatins,"In this paper we describe enantioselective syntheses of (+)-carbapentostatin (8) and its cyclopentyl analogue 12b. A new and efficient one-pot, two-step preparation of aldehyde 15 has been developed, based on the borane reduction of N-Pf-protected L-aspartic acid gamma-methyl ester (13) and Swern oxidation of the resulting alcohol. Homologation to diester 18 and ring formation by Dieckman cyclization, followed by reduction and dehydration steps, afford the 4-amino-1-cyclopentenemethanol derivative 22. Hydroboration and oxidation transform this compound stereospecifically into aminocyclopentanol 26, the key aminocyclitol component for an asymmetric synthesis of (+)-carbapentostatin.",10.1021/jo020612x,2002-12-12,0.7008468776473692
Organic Process Research & Development,"Process Development in the Synthesis of the ACE Intermediate MDL 28,726","MDL 28,726 is a key intermediate in the synthesis of the ACE inhibitors MDL 27,210A and MDL 100,240. An efficient nine-step synthesis of this tricyclic acid, which has three chiral centers, was developed beginning with 3,4-dihydro-2 H -pyran. A key step in the synthesis features an enzyme-catalyzed resolution of the lithium salt of the N -trifluoroacetamide of ( R,S )-6-hydroxynorleucine. All of the steps were optimized and completed in reactor equipment using environmentally acceptable processes. Process development of this route is described.",10.1021/op970125x,1999-06-05,0.7008096811416963
Organic Process Research & Development,Palladium-Catalyzed C–O Cross-Coupling as a Replacement for a Mitsunobu Reaction in the Development of an Androgen Receptor Antagonist,"A scalable and efficient synthesis of N -{ trans -4-[(8-cyanoquinolin-4-yl)oxy]cyclohexyl}-3-fluorobenzamide (BAY 1161116), an androgen receptor antagonist, is reported. The original synthesis included a low-yielding Mitsunobu reaction and employed cis -aminocyclohexanol, which is accessible only via a troublesome synthesis, as a key building block. The novel synthetic pathway starts from readily available trans -aminocyclohexanol and features a palladium-catalyzed etherification reaction in place of the Mitsunobu reaction as the key step. This four-step synthesis can be performed reliably on a multikilogram scale, and purification of all intermediates as well as the final product can be achieved by simple extraction and crystallization procedures.",10.1021/acs.oprd.0c00484,2021-02-18,0.7008030826614088
Tetrahedron,"Synthesis of haginin E, equol, daidzein, and formononetin from resorcinol via an isoflavene intermediate",,10.1016/j.tetlet.2009.02.159,2009-02-26,0.7007976709241641
Tetrahedron,Synthesis of 1-alkylselenocyclobutene via intermediate allenyl selenoketene,,10.1016/j.tetlet.2005.01.019,2005-01-29,0.7007976709241641
Tetrahedron,"Synthesis of “pre-presqualene′, a predicated intermediate in presqualene biosynthesis, and of prenylogues",,10.1016/s0040-4039(00)87143-9,1982-01-01,0.7007976709241641
Tetrahedron,Synthesis of glucosylphosphatidylglycerol via a phosphotriester intermediate.,,10.1016/s0040-4039(01)95462-0,1979-01-01,0.7007976709241641
Synthesis,"Synthesis of 2-(6-Methoxycarbonylhexyl)-cyclopentane-1,3,4-trione, A Prostaglandin Intermediate",,10.1055/s-1978-24786,1978-01-01,0.7007976709241641
Synthesis,Synthesis of a Prostanoid Intermediate,,10.1055/s-1974-23318,1974-01-01,0.7007976709241641
Organic Letters,Total Synthesis of (+)-18-<i>epi-</i>Latrunculol A,"An enantioselective total synthesis of the cytotoxic latrunculin congener (+)-18-epi-latrunculol A has been achieved. Key steps in the synthetic route include an acid-mediated enone cyclization/equilibration sequence, a Carreira alkynylation, and a late-stage Mitsunobu macrolactonization to construct the macrolide skeleton.",10.1021/ol4021892,2013-08-23,0.7007527202299578
Organic Process Research & Development,Development of a Scalable Process for the Insecticidal Candidate Tyclopyrazoflor. Part 1. Evaluation of [3 + 2] Cyclization Strategies to 3-(3-Chloro-1<i>H</i>-pyrazol-1-yl)pyridine,"The evaluation of [3 + 2] cyclization strategies to prepare a key intermediate, 3-(3-chloro-1 H -pyrazol-1-yl)pyridine, for the insecticidal candidate tyclopyrazoflor ( 1 ) is described. Among the validated strategies, the route involving [3 + 2] cyclization of 3-hydrazinopyridine·2HCl with methyl acrylate was selected for further optimization. This route provided ready access to 3-(3-chloro-1 H -pyrazol-1-yl)pyridine in three steps via cyclization, chlorination, and oxidation. Further functionalization of 3-(3-chloro-1 H -pyrazol-1-yl)pyridine via nitration, reduction, and amide formation with 3-((3,3,3-trifluoropropyl)thio)propanoic acid followed by ethylation rendered 1 in a total of seven steps.",10.1021/acs.oprd.9b00127,2019-07-01,0.70070626960218
Organic Process Research & Development,Development of a Scalable Stereoselective Synthesis of Selected Potent ROMK Inhibitors,"An efficient and scalable synthesis of two small-molecule renal outer medullary potassium (ROMK) inhibitors 1 and 2 was developed from readily available raw material. The alternative approach includes a newly developed asymmetric reduction of the keto intermediate to access compound 1 and a chiral resolution of an amine intermediate for the synthesis of compound 2, respectively, which circumvented the large-scale supercritical fluid chromatography (SFC) separation of the homochiral intermediates. A safe, robust, and scalable synthesis of 1 and 2 was successfully demonstrated.",10.1021/acs.oprd.4c00421,2025-01-31,0.7006559573202196
Journal of the American Chemical Society,Nine-Step Enantioselective Total Synthesis of (−)-Vincorine,"A concise and highly enantioselective total synthesis of the akuammiline alkaloid (-)-vincorine has been accomplished. A key element of the synthesis is a stereoselective organocatalytic Diels-Alder, iminium cyclization cascade sequence, which serves to construct the tetracyclic alkaloid core architecture in one step from simple achiral precursors. The challenging seven-membered azepanyl ring system is installed by way of a single electron-mediated cyclization event initiated from an acyl telluride precursor. The total synthesis of (-)-vincorine is achieved in nine steps and 9% overall yield from commercially available starting materials.",10.1021/ja402933s,2013-04-15,0.7006357240049839
Organic Process Research & Development,Some Issues and Their Solutions in the Process Development of Ethyl 2-(4-Aminophenoxy)thiazole-5-carboxylate: A Key Intermediate of P2X<sub>3</sub> Antagonist,"Ethyl 2-(4-aminophenoxy)thiazole-5-carboxylate is a key intermediate of several P2X 3 antagonists required for clinical trials. The synthesis at the early R&D stage delivered this thiazole derivative via a nucleophilic aromatic substitution reaction in highly variable yields, from 7 to 85%. We describe the process development of the initial route of synthesis carefully considering the reaction conditions, process robustness and safety, operational improvement, and the impact on downstream steps. The optimized process was successfully replicated on a multikg scale in a pilot plant, allowing for the supply of the key intermediate in 90% isolated yield with high purity (>99 area%).",10.1021/acs.oprd.5c00015,2025-03-11,0.7006354304976902
Organic Process Research & Development,Route Scouting and Process Development of Lu AA26778,"Route scouting and process development for the synthesis of ( S )-2-({3-[( S )-5-chloro-1-(4-chloro-phenyl)indan-1-yl]propyl}methylamino)propionic acid, Lu AA26778, are described. The strategy is based on a short synthesis and SMB resolution of a key chiral intermediate for the introduction of one of the two stereocenters. The second stereocenter is introduced via a commercially available alanine ester, optionally bearing a N -methyl group. The main concern during scale-up of the synthesis was the safety of a step incorporating sodium dimsylate (the sodium salt of DMSO): this problem was solved using THF as a safety blanket in the large-scale process.",10.1021/op7002584,2008-05-01,0.7005677827939831
Organic Letters,Total Synthesis of (+)-<i>epi</i>-Condyfoline,"Herein, we report the first asymmetric total synthesis of aspidospermatan indole alkaloid (+)- epi -condyfoline ( 1 ) in 15 steps from commercially available 2-methylindole-3-carboxaldehyde. Key steps include (1) our domino Michael/Mannich annulation method of N -sulfinyl metallodienamines to set three contiguous stereocenters, (2) LiHMDS-mediated cyclization of an ω-tosyloxy N -sulfinamide to prepare the signature indole-fused 2-azabicyclo[3.3.1]nonane framework, and (3) DMTSF-promoted spirocyclization of a dithioacetal intermediate to access the final pyrrolidine ring. Functional group manipulations delivered the targeted alkaloid (+)- epi -condyfoline ( 1 ) in 13 steps and 1.25% overall yield from N -sulfinylimine (+)- 8 .",10.1021/acs.orglett.9b03762,2019-11-18,0.7004881239123768
Organic Process Research & Development,Application of Biocatalytic Reductive Amination for the Synthesis of a Key Intermediate to a CDK 2/4/6 Inhibitor,"Biocatalytic reductive amination catalyzed by engineered imine reductase (RedAms) is a new and powerful tool for the synthesis of substituted chiral amines. Herein, we describe a streamlined synthesis of compound 3, a key intermediate to a CDK 2/4/6 inhibitor 1, relying on the enzymatic reductive amination of a hydroxyketone to introduce the chiral secondary amine with high diastereoselectivity. The improved synthesis of the hydroxyketone precursor by a titanium-catalyzed reductive cyclization and the process development for two S N Ar reactions en route to 3 are also presented.",10.1021/acs.oprd.1c00255,2021-09-03,0.700478819137232
European Journal of Organic Chemistry,Total Synthesis of Two 8‐Oxoprotoberberine Alkaloids: Alangiumkaloids A and B,"A new and versatile synthetic route for 8‐oxoprotoberberine 17 through synthesis of isoquinolinone 16 and construction of a B‐ring is described. The key step is the synthesis of isoquinolinone 14 through thermal cyclization of 2‐alkynylbenzaldehyde oxime 12 to afford isoquinoline N ‐oxide 13 , followed by a Reissert–Henze‐type reaction. The first total synthesis of 8‐oxoprotoberberine alkaloid alangiumkaloids A and B was achieved by using this strategy.",10.1002/ejoc.201701557,2018-01-09,0.7004518424002191
Synthesis,Modified Synthesis of NOP Receptor Antagonist SB612111,"SB612111 [(5 S ,7 S )-7-{[4-(2,6-dichlorophenyl)piperidin-1-yl]methyl}-1-methyl-6,7,8,9-tetrahydro-5 H -benzo[7]annulen-5-ol] is a potent and selective antagonist of the nociception/orphanin FQ peptide (NOP) receptor. In the process of synthesizing cis -SB612111 to support ongoing animal studies, several key steps of the published syntheses in the patent literature proceeded in low yields in our hands, particularly in the route to the key intermediate 4-(2,6-dichlorophenyl)piperidine, the reduction of 7-[4-(2,6-dichlorophenyl)piperidine-1-carbonyl]-1-methyl-6,7,8,9-tetrahydro-5 H -benzo[7]annulen-5-one, the formation of (±)-6-methyl-12-oxatricyclo[8.2.1.0 2,7 ]trideca-2,4,6-trien-11-one, and the final reductive amination between (±)-6-methyl-12-oxatricyclo[8.2.1.0 2,7 ]trideca-2,4,6-trien-11-ol and 4-(2,6-dichlorophenyl)piperidine in the diastereoselective synthesis. We have thus explored various reaction conditions and successfully improved the yields for the necessary synthetic steps. We herein report our modified synthesis of SB612111 as the cis -diastereomers.",10.1055/s-0036-1588379,2016-12-19,0.7004165850459129
Tetrahedron,"A practical asymmetric synthesis of a 1,7-enyne A-ring synthon en route toward the total synthesis of vitamin D3 analogues","A concise synthesis of a key A-ring synthon of 1α,25-dihydroxyvitamin D3, 1, has been achieved in 8 steps starting from readily available, inexpensive ethyl-4-chloroacetoacetate. This synthon serves as one of two main coupling partners in our previously developed Pd-catalyzed alkylative enyne cyclization leading toward the total synthesis of 1α,25-dihydroxyvitamin D3 and potentially useful analogues.",10.1016/0040-4039(94)88259-2,1994-10-01,0.7003906645142484
Organic Letters,Total Synthesis of Tryprostatin B: Synthesis and Asymmetric Phase-Transfer-Catalyzed Reaction of Prenylated Gramine Salt,"A concise and efficient total synthesis of microtubule inhibitor tryprostatin B (1) is described. The key step is the preparation of a diprenylated gramine salt 9a. In this step, the prenyl group is incorporated at the 2-position of the indole moiety by direct lithiation of the Boc-protected gramine. We also developed and optimized the asymmetric phase-transfer-catalyzed reaction with salt 9a to provide the C2-prenyl tryptophan intermediate 2 resulting in 93% enantiomeric excess (ee) and 65% yield. The total synthesis of 1 is done in six steps with 35% overall yield.",10.1021/acs.orglett.8b03593,2018-12-18,0.7002736934641537
Journal of the American Chemical Society,Enantioselective Total Synthesis of Quadrigemine C and Psycholeine,"The first total syntheses of higher-order members of the polypyrrolidinoindoline alkaloid family are reported. The synthesis of quadrigemine C (1) and psycholeine (3) begins with synthetic meso-chimonanthine (4), which is synthesized from commercially available oxindole and isatin in 13 steps and 35% overall yield. Double Stille cross coupling of diiodide 7, available in three steps from 4, with vinylstannane 8 produces dibutenanilide 9. Double catalytic asymmetric Heck cyclization of 9 simultaneously installs the two peripheral quaternary stereocenters and desymmetrizes this advanced meso precursor to deliver the chiral, decacyclic intermediate 11 in 62% yield and 90% ee. In two additional steps, 11 is converted to 1, which upon treatment with acid generates 3. The synthesis of quadrigemine C (1), which rigorously confirms its relative and absolute configuration, was executed in 19 linear steps (2% overall yield) from commercially available starting materials.",10.1021/ja0267425,2002-07-10,0.7002736858827915
Organic Process Research & Development,"Development of a Rapid Scale-Up Synthesis of (<i>S</i>)-<i>N</i>-(8-((2-Amino-2,4-dimethylpentyl)oxy)-5<i>H</i>-chromeno[3,4-<i>c</i>]pyridin-2-yl)acetamide, a Potent Adaptor-Associated Kinase 1 Inhibitor","( S )- N -(8-((2-Amino-2,4-dimethylpentyl)oxy)-5 H -chromeno[3,4- c ]pyridin-2-yl)acetamide ( 1 ) is a potent adaptor-associated kinase 1 inhibitor, which may have the potential to treat neuropathic pain and other neurological disorders including schizophrenia, Parkinson’s disease, bipolar disorder, and Alzheimer’s disease. For preclinical studies, a substantial amount of high-quality material was required. The original discovery route for the preparation of this compound suffered from scale-up issues that included a very low-yielding C–O coupling step and the use of expensive and toxic reagents. This paper describes a rapid scale-up synthesis accomplished in eight steps, which involves the coupling of phenol 17 with oxathiazolidine 18 as the key transformation.",10.1021/acs.oprd.1c00452,2022-01-31,0.7002651035844784
Organic Process Research & Development,Development of Two Synthetic Approaches to an APJ Receptor Agonist Containing a Tetra-<i>ortho-</i>Substituted Biaryl Pyridone,"The development and implementation of two process syntheses to provide BMS-986224, an agonist of the APJ receptor, are reported. The first-generation synthesis of BMS-986224 relied on a key enamine cyclization to construct the pyridone core; however, the overall efficiency of this route was limited by the linear synthesis of the hindered biaryl pyridone. This lack of convergence is solved in a second-generation route that minimizes low-temperature lithiation chemistry, replaces costly Pd coupling with scalable nucleophilic arylation, and reduces step count. The improved synthesis was enabled by a new Negishi coupling method that addresses limitations of the Suzuki–Miyaura literature for tetra- ortho -substituted biaryl pyridones.",10.1021/acs.oprd.1c00088,2021-04-22,0.7002028893337574
Organic Process Research & Development,"Investigation of Methods for Seven-Membered Ring Synthesis:  A Practical Synthesis of 4-Oxo-5,6,7,8-tetrahydro-4H-cyclohepta[<i>b</i>]furan-3-carboxylic Acid","Several synthetic routes to 4-oxo-5,6,7,8-tetrahydro-4H-cyclohepta[ b ]furan-3-carboxylic acid ( 1 ) are described, and the scale-up issues with each route are discussed. Seven-membered ring formation is a key issue with these syntheses, and several strategies are presented, including preparation from cycloheptane-1,3-dione, ring-expansion routes, Dieckmann cyclization, acetylene-furan [4 + 2] cycloaddition, and Friedel−Crafts cyclization. Two of the routes were scaled in the pilot plant to provide kilogram quantities of the title compound. The first scale-up route is outlined in Scheme 2 and utilizes a ring-expansion strategy to prepare cycloheptane-1,3-dione from cyclopentanone, via a [2 + 2] cycloaddition between dichloroketene and the silyl enol ether of cyclopentanone. The diketone is converted to the title compound by condensation with ethyl bromopyruvate and base, followed by acid hydrolysis. This route was efficient on laboratory scale but encountered problems upon scale-up due to a competing fragmentation pathway in the Zn/AcOH-mediated retro-aldol of cyclobutanone 11 . The second, more successful scale-up route is described in Scheme 15, and involves Friedel−Crafts acylation of 3-carboethoxyfuran selectively at the 5-position. Reduction, lactonization, and hydrogenolysis provide acid 43, which is cyclized via a second Friedel−Crafts reaction to form the seven-membered ketone.",10.1021/op0102159,2001-07-25,0.7001882734148479
Organic Process Research & Development,Enabling the First Scale-Up of the Selective HER2 Inhibitor BI-4142,"The enabling synthesis of the first route to HER2 inhibitor BI-4142 ( 1 ) to deliver a drug substance in kilogram quantity is reported. The synthetic route involves (1) a fit-for-purpose synthesis of pyrimido[5,4- d ]pyrimidine 2; (2) a high yielding, scalable synthesis of aniline 3; (3) a safer sodium tungstate-catalyzed sulfide oxidation; (4) S N Ar reactions to form C–N bonds; and (5) amidation via Schotten–Baumann conditions. With the speed of delivery prioritized, a purification protocol using silica gel filtration and crystallizations was developed in time to control the quality of API. The overall yield of the delivery route was improved from 22% to 46% over a prior route starting from 2 .",10.1021/acs.oprd.5c00127,2025-05-14,0.7001311692380234
European Journal of Organic Chemistry,Enantioselective Total Synthesis of (+)‐Vittatalactone,"Abstract An enantioselective asymmetric total synthesis of (+)‐vittatalactone has been accomplished employing enzymatic desymmetrization approach to create two methyl chiral centres. Other key steps involved are Wittig reaction, Evan's asymmetric alkylation, hydroboration, TEMPO‐BAIB‐mediated selective oxidation of 1,3‐diol and lactonization mediated by p ‐toluenesulfonyl chloride. The total synthesis was achieved by a linear synthetic sequence with an overall yield of 11.8 %.",10.1002/ejoc.201100354,2011-06-21,0.7001256245899653
Journal of Organic Chemistry,A Formal Synthesis of (−)-Perhydrohistrionicotoxin Using a Cross Metathesis–Hydrogenation Approach,"The development of an efficient, high yielding six-step convergent synthesis of the semisynthetic alkaloid (-)-perhydrohistrionicotoxin is described. The key transformations include the cross metathesis of a Brønsted-acid masked primary homoallylic amine with a vinyl cyclohexenone and a regioselective palladium catalyzed hydrogenation. This sequence generated the advanced Winterfeldt spirocyclic precursor in 47% overall yield, with a longest linear sequence of five steps.",10.1021/acs.joc.7b01257,2017-07-21,0.6999483671399672
Journal of Organic Chemistry,Development of a Concise and Robust Route to a Key Fragment of MCL-1 Inhibitors via Stereoselective Defluoroborylation,"MCL-1 is an attractive target for cancer therapy. We recently discovered highly potent and selective MCL-1 inhibitors containing a fluoroalkene fragment for which an efficient route to the main chiral gem -fluoro-BPin fragment was needed. The key step of this synthesis is a highly stereoselective defluoroborylation of a gem -difluorovinyl intermediate. The latter is reached via a copper-catalyzed diastereoselective opening of dimethyloxirane. These two features allowed a 30-fold improvement in yield, a shorter synthesis, and a decrease in the cost of this crucial building block.",10.1021/acs.joc.1c01666,2021-09-27,0.6999056696259398
Journal of the American Chemical Society,Novel Syntheses of Tetrahydropyrroloquinolines:  Applications to Alkaloid Synthesis,"Two novel routes involving the intramolecular olefin insertion with a zirconium−benzyne complex, followed by a palladium-catalyzed aryl amination, have been developed for the synthesis of tetrahydropyrroloquinolines. In one approach, exemplified in the six-step total synthesis of the South American toad poison dehydrobufotenine ( 1 ), the tricyclic system was formed via the Pd-catalyzed ring closure of a functionalized tryptamine derivative. In the second, cyclization of an appropriately substituted quinoline yields 13, an intermediate in the synthesis of damirones A and B, and also makaluvamine C, a topoisomerase II inhibitor exhibiting antitumor properties.",10.1021/ja953080t,1996-01-01,0.699893027319456
European Journal of Organic Chemistry,"A Practical Synthesis of (2S,3R,4S)-4-Hydroxyisoleucine, A Potent Insulinotropic α-Amino Acid from Fenugreek","An efficient eight-step synthesis of optically pure (2S,3R,4S)-4-hydroxyisoleucine (1), a potent insulinotropic α-amino acid found in the seeds of fenugreek (Trigonella foenum-graecum L.), is achieved in 39% overall yield. The method is suitable for large-scale production of the title compound. The key steps involve the biotransformation of ethyl 2-methylacetoacetate to ethyl (2S,3S)-2-methyl-3-hydroxybutanoate (2) with Geotrichum candidum and an asymmetric Strecker synthesis. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)",10.1002/1099-0690(200203)2002:5<834::aid-ejoc834>3.0.co;2-6,2002-03-01,0.6997780932035853
Organic Process Research & Development,"Development of a Two-Step, Enantioselective Synthesis of an Amino Alcohol Drug Candidate","The process development and large scale synthesis for the β-hydroxyamino amide 1 is described. The route evolved from a multistep sequence utilizing a classical resolution to a two-step enantioselective process involving an enzyme-catalyzed aldol reaction and a direct amidation of a carboxylic acid. By utilizing a silicon-mediated direct amidation strategy, the route was devoid of protecting and deprotecting steps while retaining the stereochemical integrity of a highly sensitive β-hydroxyamino acid. The two-step strategy employed herein significantly improved the yield, process greenness, cycle time, and estimated cost in the production of 1 .",10.1021/acs.oprd.5b00192,2015-07-03,0.6996497852685679
Organic Process Research & Development,"Process Development of Tryptophan Hydroxylase Inhibitor LX1031, a Drug Candidate for the Treatment of Irritable Bowel Syndrome","Two process routes for LX1031, a tryptophan hydroxylase inhibitor for the treatment of irritable bowel syndrome, were developed. They shared the same left-hand and right-hand starting materials as well as the penultimate intermediate. The chiral center in the left-hand moiety was established via a Noyori asymmetric hydrogenation of a trifluoromethyl aryl ketone. The right-hand boronate was prepared via a palladium-catalyzed borylation of l -tyrosine-derived aryl triflate. Union of these two fragments to the pyrimidine core, from the right- or left-hand side, constituted the first- and second-generation routes, respectively. Removal of the Boc-protecting group from the penultimate intermediate gave LX1031. The challenges overcome in purification and isolation of the LX1031 zwitterion are also discussed. Both process routes were successfully performed on multikilogram scales to supply LX1031 API for the preclinical and clinical studies.",10.1021/acs.oprd.9b00520,2020-01-20,0.6996434990408739
Organic Process Research & Development,Development of a Modified Process for the Kilogram-Scale Synthesis of c-Met/ALK Inhibitor HS-10168,"A modified synthetic route to c-Met/ALK inhibitor HS-10168 has been developed on a kilogram scale. The key steps of the new process include a Suzuki coupling reaction of nitro-containing bromopyridine 6 and para -phenol boronate 9 to give intermediate 10, which was then converted to its triflate 11 . The phosphorus group was introduced by coupling of 11 and dimethylphoshine oxide 8 to give compound 12, which was reduced to produce HS-10168.",10.1021/acs.oprd.6b00402,2017-01-06,0.6995758567030196
Angewandte Chemie International Edition,"A General Entry to Antifeedant Sesterterpenoids: Total Synthesis of (+)‐Norleucosceptroid A, (−)‐Norleucosceptroid B, and (−)‐Leucosceptroid K","The first asymmetric total synthesis of the antifeedant terpenoids (+)-norleucosceptroid A, (-)-norleucosceptroid B, and (-)-leucosceptroid K has been accomplished. This highly concise synthetic route was guided by our efforts to develop a platform for the collective synthesis of a whole family of antifeedant natural products. The synthesis features a Hauser-Kraus-type annulation followed by an unprecedented, highly efficient intramolecular dilactol aldol-type condensation reaction to produce the 5,6,5 skeleton. The developed synthetic route proceeds for norleucosceptroid A and B in 16 steps (longest linear sequence) from known compounds.",10.1002/anie.201407788,2014-09-04,0.6995121336991182
Organic Letters,Enantioselective Total Synthesis of Diocollettines A,"The first enantioselective total synthesis of diocollettines A was accomplished in only six steps from a known compound. A short and practical synthetic route was disclosed, featuring an intensive investigation of the stereoselective aldol reaction as a key step using an easily prepared aldehyde moiety and an enone derivative. The synthetic scheme also includes the efficient stereocontrolled construction of the tricyclic skeleton of diocollettines A by intramolecular acetal formation, stereoselective dihydroxylation, and intramolecular ether cyclization.",10.1021/acs.orglett.9b01776,2019-06-27,0.6995092818518556
European Journal of Organic Chemistry,Total Synthesis of Lophirone F Hexamethyl Ether,"A practical and efficient approach for the total synthesis of the (±)‐lophirone F hexamethyl ether was reported. The compound was synthesized in 8 steps with a 14.6 % overall yield. The key features of this synthesis are the stereoselective synthesis of a 2,5‐diaryl‐3,4‐disubstituted tetrahydrofuran skeleton via a sequence of [3+2] cycloaddition/Krapcho decarboxylation and the installation of two aryl ketone groups bypassing potential epimerization of adjacent stereocenters.",10.1002/ejoc.201801827,2019-02-05,0.6994761375751392
Organic Process Research & Development,Improved Manufacturing Route and Polymorphic Control of a Potent and Selective Anaplastic Lymphoma Kinase (ALK) Inhibitor ASP3026,"Our effort toward the process improvement of anaplastic lymphoma kinase (ALK) inhibitor ASP3026 ( 1 ) is described. A cost-effective and practical synthesis of 1 was accomplished as a result of the change of starting material from 2,4-dichloro-1,3,5-triazine ( 6 ) to cyanuric chloride ( 9 ) and late-stage introduction of a highly reactive N -methyl piperazine moiety by reductive amination of intermediate ketone 13 . The modified process avoided the challenges with the original synthesis and furnished the several hundred kilograms of high-quality API with high economic efficiency, operability, and reproducibility. Furthermore, a sequence of investigation of polymorphic control in the second-generation synthetic route to obtain the thermodynamically desired, most stable polymorph Form A04 is also discussed.",10.1021/acs.oprd.8b00427,2019-02-20,0.6993350525131223
Organic Process Research & Development,Development of the Route of Manufacture of an Oral H<sub>1</sub>−H<sub>3</sub> Antagonist,A new route to an H 1 −H 3 antagonist was developed to address scalability and environmental and cost of goods issues associated with the initial route.,10.1021/op1002598,2010-11-30,0.699295791056224
European Journal of Organic Chemistry,Total Synthesis of (+)‐Awajanomycin,"Abstract The total synthesis of (+)‐awajanomycin has been achieved by asymmetric allylboration of a vicinal tricarbonyl compound as the key step. A substrate‐controlled dihydroxylation and subsequent differentiation of diastereotopic ester groups were used to synthesize the γ‐lactone substructure. After formation of the δ‐lactam, the bicyclic core structure was established. The synthetic strategy and overall efficacy is compared with Huang's route to awajanomycin.",10.1002/ejoc.201200059,2012-02-29,0.6992572959099763
Organic Process Research & Development,Process Development of the Synthetic Route to R116301,"We describe in this paper the synthesis of compound 1 (R116301), which was developed to prepare pilot scale quantities (20–50 kg) of drug substance. The synthesis involves the s BuLi deprotonation of Boc-protected piperidone acetal 2, followed by benzaldehyde addition and ring closure to cyclic carbamate 4 . Piperidine acetal 5 is resolved with Brown’s acid and acylated. The ketone obtained after piperidine acetal deprotection undergoes reductive amination with N -benzyl piperazine, the most critical step in the synthesis. After debenzylation, final coupling and salt formation, compound 1 is obtained over 10 steps with 4% overall yield.",10.1021/op700086d,2007-11-01,0.6991746601707494
Tetrahedron,A highly stereocontrolled route to 2-(2′-oxiranyl)piperidines and pyrrolidines: enantioselective synthesis of (+)-α-conhydrine,,10.1016/j.tetlet.2008.09.095,2008-09-21,0.699046037680691
Organic Process Research & Development,Development of a Large Scale Asymmetric Synthesis of Vanilloid Receptor (TRPV1) Antagonist ABT-102,"A highly efficient asymmetric synthesis of TRPV1 antagonist ABT-102 was developed and successfully demonstrated on a multi-kilogram scale. This process incorporates a new asymmetric synthesis of ( R )- tert -butylaminoindan, which is based on a chiral auxiliary induced diastereoselective reduction of its iminoindan precursor.",10.1021/op060228s,2007-02-23,0.6990242463714481
Organic Process Research & Development,Efficient Synthesis of a Key Intermediate for Moxifloxacin Via Intramolecular Double Stereodifferentiation,"An intramolecular double stereodifferentiation methodology was developed during the synthetic process development of ( S, S )-2,8-diazobicylo[4.3.0] nonane ( 1 ), the key intermediate of the fourth-generation fluoroquinolone Moxifloxacin. The dual chiral-auxiliary strategy employed in this process guaranteed high stereoselectivity of the hydrogenation reaction to build the cis-[5,6] bicyclic system with desired stereochemistry. 1,6-Bis(( R )-1-phenylethyl)-3,4,6,7-tetrahydro-1 H -pyrrolo[3,4- b ]pyridine-2,5-dione ( 11f ), the precursor of the hydrogenation reaction, was prepared from commercially available and affordable chemicals ethyl acetoacetate, ( R )-(+)-1-methylbenzylamine, and acryloyl chloride, and the process was further facilitated by telescoping the first three steps into one pot. Moreover, this process has been proven robust at a hectogram scale, providing 450 g of intermediate 1 with a total yield of 56.2% over seven steps and enantiomeric excess of more than 99%, demonstrating the potential for commercial-scale applicability.",10.1021/acs.oprd.2c00183,2022-07-28,0.6990049032062973
Tetrahedron,A route to the preparation of γ-hydroxyvinylstannanes,,10.1016/s0040-4039(00)94706-3,1990-01-01,0.6989547279305018
Journal of Organic Chemistry,A Highly Efficient Pinacol Coupling Approach to Trehazolamine Starting from <scp>d</scp>-Glucose,"A short and very efficient synthesis of trehazolamine (3), the aglycon of the potent trehalase inhibitor trehazolin (2), has been achieved starting from D-glucose. The key transformation in this approach is a high-yielding two-step, one-pot sequence consisting of a Swern oxidation of a 1,5-diol followed by a reductive carbocyclization of the resultant 1,5-dicarbonyl compound promoted by samarium diiodide. The overall yield of 3 is 39% over nine steps from 2,3,4,6-tetra-O-benzyl-D-glucose (5). An even shorter synthesis of 30, a diastereoisomeric analogue of 3, is also described starting from 5. The key transformation in this second route is a highly stereoselective ketone oxime ether reductive carbocyclization promoted also by samarium diiodide. The overall yield of 30 is 57% over four steps from 5.",10.1021/jo980831b,1998-07-30,0.6989536502260063
Organic Process Research & Development,"Practical Synthesis of Chiral 3-(Hydroxyiminomethyl)adipic Acid, a Key Intermediate of the ROR-γ Inhibitor JTE-151, via Crystallization-Induced Dynamic Resolution","A practical six-step process for the production of chiral 3-(hydroxyiminomethyl)adipic acid 4 featuring highly efficient crystallization-induced dynamic resolution (CIDR) as the key step is reported. This compound was converted to isoxazole 23, an API starting material candidate of the ROR-γ inhibitor JTE-151, via isoxazole core construction by 1,3-dipolar cycloaddition and subsequent Ag 2 O-catalyzed decarboxylation of the tentatively introduced carboxyl group on the isoxazole core.",10.1021/acs.oprd.3c00320,2023-11-20,0.6989068183857157
Journal of Organic Chemistry,The Shortest Synthetic Route to Puromycin Analogues Using a Modified Robins Approach,We are reporting on the utility of commercial vinyl isocyanate for a practical synthetic route from adenosine to N(6)-bis-demethylpuromycin in seven steps and 65% overall yield. A clean one-pot conversion of 3'-bromo-2'-carbamoyl derivative 8 to 3'-amino-3'-deoxyadenosine derivative 10 is the main feature of this synthetic pathway. This synthesis is the shortest synthetic route toward 3'-(aminoacylamido)deoxyadenosines to date.,10.1021/jo102178h,2011-03-01,0.6988840890020575
Organic Process Research & Development,Development and Scale-Up of an Optimized Route to the Pyridazin-3-one Histamine H3 Receptor Antagonist CEP-32215,"The evolution of the process to prepare CEP-32215, 3-(1′-cyclobutylspiro[4H-1,3-benzodioxine-2,4′-piperidine]-6-yl)-5,5-dimethyl-1,4-dihydropyridazine-6-one, is presented. Two routes detailing preparation of supplies for biological screening are discussed along with the optimized fit-for-purpose process used to prepare several hundred grams for preclinical testing. Details on the development of the formation of the key spiroketal moiety are presented along with the discovery of a novel Suzuki coupling approach for synthesis of the backbone of the molecule.",10.1021/op400039d,2013-03-22,0.6988809900164091
Organic Process Research & Development,Development of a Scalable Method for Manufacturing the Central Core of CD73 Inhibitor AB680,"AB680 is a highly potent CD73 small molecule inhibitor discovered and developed by Arcus Biosciences, currently in clinical trials for the treatment of pancreatic cancer. Here, we report the development of a scalable and practical method for the manufacturing of the azaindazole central core. This synthesis features an N -oxide formation followed by an α-chlorination with POCl 3 leading to the formation of 4,6-dichloro-1 H -pyrazolo[3,4- b ]pyridine 1 in high yield and 99.5% UV purity. This method was successfully performed on multikilogram scale to support the synthesis of AB680.",10.1021/acs.oprd.0c00469,2020-12-12,0.6988254051324191
European Journal of Organic Chemistry,"Synthesis of Racemic δ,δ‐Dimethylproline Derivatives","Abstract A versatile methodology for the preparation of racemic δ,δ‐dimethylproline derivatives has been developed. Methyl N ‐Boc‐δ,δ‐dimethylprolinate was synthesized from a β‐amino acid in six steps and 55 % overall yield. The route is amenable to the preparation of a broad range of δ,δ‐disubstituted prolines by starting with the adequate β‐amino acids. In addition, one of the intermediate compounds in the synthetic route has been used for the preparation of a δ,δ‐dimethylproline derivative that is substituted at the β‐position with a phenyl group. This has been achieved by coupling phenylboronic acid with a regioselectively generated vinyl triflate followed by a stereoselective hydrogenation.",10.1002/ejoc.201201420,2013-01-11,0.6988111837327883
Tetrahedron,"5 (S), 6(R)-5. 7-dibenzoyloxy-6-hydroxyheptanoate ester: improved synthesis of a leukotriene intermediate",,10.1016/s0040-4039(01)81985-7,1981-01-01,0.6987926763342645
Journal of the American Chemical Society,Asymmetric Synthesis of Chiral Organofluorine Compounds:  Use of Nonracemic Fluoroiodoacetic Acid as a Practical Electrophile and Its Application to the Synthesis of Monofluoro Hydroxyethylene Dipeptide Isosteres within a Novel Series of HIV Protease Inhibitors,"Two stereoselective routes to a series of diastereomeric inhibitors of HIV protease, monofluorinated analogues of the Merck HIV protease inhibitor indinavir, are described. The two routes feature stereoselective construction of the fluorinated core subunits by asymmetric alkylation reactions. The first-generation syntheses were based on the conjugate addition of the lithium enolate derived from pseudoephedrine alpha-fluoroacetamide to nitroalkene 12, a modestly diastereoselective transformation. A more practical second-generation synthetic route was developed that is based on a novel method for the asymmetric synthesis of organofluorine compounds, by enolate alkylation using optically active fluoroiodoacetic acid as the electrophile in combination with a chiral amide enolate. Resolution of fluoroiodoacetic acid with ephedrine provides either enantiomeric form of the electrophile in > or = 96% ee. Alkylation reactions with this stable and storable chiral fluorinated precursor are shown to proceed in a highly stereospecific manner. With the development of substrate-controlled syn- or anti-selective reductions of alpha-fluoro ketones 44 and 45 (diastereomeric ratios 12:1-84:1), efficient and stereoselective routes to each of the four targeted inhibitors were achieved. The optimized synthetic route to the most potent inhibitor (syn,syn-4, K(i) = 2.0 nM) proceeded in seven steps (87% average yield per step) from aminoindanol hydrocinnamide 40 and (S)-fluoroiodoacetic acid, and allowed for the preparation of more than 1 g of this compound. The inhibition of HIV-1 protease by each of the fluorinated inhibitors was evaluated in vitro, and the variation of potency as a function of inhibitor stereochemistry is discussed.",10.1021/ja010113y,2001-07-07,0.6987529019748733
Organic Process Research & Development,Initial Process Development and Scale-Up of the Synthesis of a Triple Reuptake Inhibitor ALB 109780,"Early process development toward a triple reuptake inhibitor is described. Three different routes were evaluated; one of them was optimized and scaled up to generate 470 g of API as this route minimized the formation of undesired side products. The selected route featured Eaton’s reagent-mediated cyclization of a phenyl acetamide, copper-mediated Buchwald–Hartwig coupling to install a morpholine moiety, and palladium-catalyzed α-arylation of a dihydroisoquinolinone to construct the core structure.",10.1021/op3000064,2012-02-13,0.6986591447928927
Organic Process Research & Development,Development of a Scalable Process for the Synthesis of DNDI-VL-2098: A Potential Preclinical Drug Candidate for the Treatment of Visceral Leishmaniasis,"High Resolution Image Download MS PowerPoint Slide A process suitable for kilogram-scale synthesis of (2 R )-2-methyl-6-nitro-2-{[4-(trifluoromethoxy)phenoxy]methyl}-2,3-dihydroimidazo[2,1- b ][1,3]oxazole (DNDI-VL-2098, 2 ), a preclinical drug candidate for the treatment of visceral leishmaniasis, is described. The four-step synthesis of the target compound involves the Sharpless asymmetric epoxidation of 2-methyl-2-propen-1-ol, 8 . Identification of a suitable synthetic route using retrosynthetic analysis and development of a scalable process to access several kilograms of 2 are illustrated. The process was simplified by employing in situ synthesis of some intermediates, reducing safety hazards, and eliminating the need for column chromatography. The improved reactions were carried out on the kilogram scale to produce 2 in good yield, high optical purity, and high quality.",10.1021/acs.oprd.6b00331,2016-12-06,0.6986561951171645
Organic Process Research & Development,A Novel Scalable Synthesis of Pramipexole,"Pramipexole is a dopamine D 2 subfamily receptor agonist that is used for the treatment of Parkinson’s disease. We report here on the successful application of the Fukuyama alkylation protocol to the development of a novel and scalable process for synthesis of pramipexole and its pharmaceutically acceptable salts. The synthesis consists of converting the crucial intermediate ( S )-2,6-diamino-4,5,6,7-tetrahydrobenzothiazole to (6 S )- N -(2-amino-4,5,6,7-tetrahydrobenzothiazole-6-yl)-2-nitrobenzenesulfonamide, which is in turn monoalkylated to (6 S )- N -(2-amino-4,5,6,7-tetrahydrobenzothiazole-6-yl)-2-nitro- N -propylbenzenesulfonamide. Deprotection of the latter yields pramipexole base, which is finally converted to a crude pramipexole dihydrochloride monohydrate with a yield of over 50% over four steps. The process allows for the telescoping of the final three steps, has high conversion rates of intermediates, offers ease of purification, and preserves high optical purity throughout all of the stages.",10.1021/op1000989,2010-07-07,0.6986167722900192
Organic Letters,Toward the Synthesis of Didemnaketal B: A Convergent Synthesis of the C9−C28 Subunit,Synthesis of the C9-C28 subunit of didemnaketal B has been developed. This subunit was convergently prepared from four chiral synthons and at the longest linear sequence required 16 steps.,10.1021/ol801395q,2008-07-24,0.6985588902890263
Organic Process Research & Development,A New Route to Prepare 6-Chloro-5-(2-chloroethyl)oxindole,"6-Chloro-5-(2-chloroethyl)oxindole, a key intermediate in the manufacturing of the antipsychotic drug, ziprasidone, has been synthesized by a new route. The salient features of the synthesis are (1) bis-dialkylation of 2,4-difluoro-5-chloronitrobenzene with sodium diethyl malonate, (2) decarboxylative hydrolysis to obtain the oxindole derivative, and (3) reduction and chlorination of acetic ester side chain.",10.1021/op020095k,2003-02-20,0.6985160579391383
Organic Letters,Total Synthesis of Neolaulimalide and Isolaulimalide,"The first total syntheses of the potential antitumoral leads neolaulimalide (2) and isolaulimalide (3) have been achieved. Key steps in our convergent, fully stereocontrolled route are a Yamaguchi macrolactonization, a Julia-Lythgoe-Kocienski olefination, a Kulinkovich reaction, and a cyclopropyl-allyl rearrangement to install the exo-methylene group. Overall, we synthesized 2 in 21 linear steps (3% yield) and 3 in 24 steps (2% yield).",10.1021/ol802075v,2008-09-25,0.698504076270984
Organic Process Research & Development,"Improved Procedures for Gram-Scale Synthesis of Galeterone 3β-Imidazole and Galeterone 3β-Pyridine Methoxylate, Potent Androgen Receptor/Mnk Degrading Agents","Galeterone ( 1 ) and its C-3 analogs are of substantial interest because of their multitarget anticancer activities, including AR and Mnk degrading activities. Here, we describe improved and efficient procedures for the gram-scale synthesis of 3β-(1 H -imidazole-1-yl)-17-(1 H -benzimidazole-1-yl)-androsta-5,16-diene (galeterone 3β-imidazole, 2 ) and 3β-(pyridine-4-ylmethoxy)-17-(1 H -benzimidazol-1-yl)androsta-5,16-diene (galeterone 3β-pyridine methoxylate, 3 ). Whereas compound 2 was synthesized in 63% overall yield from galeterone ( 1 ) over four steps, via key intermediate, 3β-azido galeterone ( 8 ); compound 3 was synthesized in 61% overall yield from 1 in one step. This article also reports on the facile synthesis of other potential AR/Mnk degrading agents (ARDAs/MNKDAs), including galeterone 3α-imidazole ( 5 ) and galeterone 3β-amine ( 10 ), both in excellent overall yields. Notably, except for the one-step synthesis of compound 3 which required purification by flash column chromatography, none of the intermediates and target compound 2 required extensive chromatographic purifications or multiple crystallizations.",10.1021/acs.oprd.6b00217,2016-08-10,0.698477500008155
Organic Process Research & Development,A Scalable Total Synthesis of Halofuginone,"A scalable total synthesis of halofuginone has been accomplished. This synthetic route features a total of 12 steps of highly efficient reactions, without any chromatographic purification. Halofuginone was obtained in 17% overall yield and over 98.5% HPLC purity. All the reaction conditions are mild and reliable. In addition, no hazardous materials are used or produced. All reagents are commercially available and inexpensive. This route is safe, robust, scalable, cost-effective, and environmentally benign.",10.1021/acs.oprd.9b00059,2019-03-06,0.698448530257152
Journal of Organic Chemistry,Gram-Scale Synthesis of an Armed Colitose Thioglycoside,"A concise gram-scale synthesis of protected colitose thioglycosides for use in bacterial carbohydrate antigen synthesis is described. The synthesis proceeds in six steps and 59-70% overall yield from commercially available l-fucose, making it the most efficient route reported to date. Key steps include regioselective installation of a thiocarbonate using catalytic dioctyltin dichloride (10 mol%) and a tris(trimethylsilyl)silane-mediated radical deoxygenation.",10.1021/jo501472v,2014-09-26,0.6983290664969758
Organic Letters,Biomimetic Total Synthesis of (−)-Isatisine A,"The biomimetic total synthesis of (-)-isatisine A, a novel alkaloid with an unprecedented fused tetracyclic skeleton, was accomplished in 8 steps from indole and 4,6-O-isopropylidene-protected glucal. The synthesis features a convergent synthetic strategy which relies on nucleophilic addition and a biomimetic benzilic ester rearrangement as key reactions.",10.1021/ol300379g,2012-02-28,0.6982964391310655
Organic Letters,Total Synthesis of Sintokamide C,"A convergent stereoselective synthesis of sintokamide C was accomplished in 14 steps with an overall yield of 3.8% starting from Garner's aldehyde, unambiguously confirming its structure.",10.1021/ol100095p,2010-02-11,0.6981929402409619
Angewandte Chemie International Edition,A Convergent Total Synthesis of the Telomerase Inhibitor (±)‐γ‐Rubromycin,"The total synthesis of the human telomerase inhibitor γ-rubromycin in its racemic form was accomplished in 3.8 % overall yield. The key feature of this synthesis is an efficient acid-catalyzed spiroketalization for the construction of the spiroketal core. The required electronically well-balanced spiroketal precursor was obtained by the convergent assembly of a naphthyl-substituted aldehyde, an α-methoxyallyl-γ-silyl-substituted phosphonate as the central C3 building block, and a highly functionalized aryl Grignard reagent. Another key feature is the late-stage construction of the isocoumarin moiety and a simultaneous protodesilylation furnishing the known methyl aryl ether protected precursor of γ-rubromycin.",10.1002/anie.201400315,2014-03-12,0.6981849421344615
Chemical Science,"A practical, convergent route to the key precursor to the tetracycline antibiotics","Here we describe a 5-step sequence to prepare the AB enone 1, the key precursor to fully synthetic tetracyclines, that begins with a diastereoselective Michael-Claisen coupling of two simple starting materials, a cyclohexenone (compound 2 or, in a refinement, a substituted variant, vide infra) and the isoxazole ester 3. This advance defines an 8-step linear sequence to 6-deoxytetracycline antibiotics from three components of similar complexity (cyclohexenone 2, isoxazole ester 3, and structurally diverse D-ring precursors) in which sequential diastereoselective Michael-Claisen cyclization reactions form the A- and C-rings, respectively, of the linearly fused ABCD tetracycline skeleton. In addition to providing a readily scalable, practical route to fully synthetic tetracyclines of broad structural diversity, the sequence reported comprises a series of non-obvious stereoselective transformations, including a novel means for C12a hydroxylation.",10.1039/c1sc00303h,2011-01-01,0.6980930304254772
Tetrahedron,"A new stereocontrolled, pyrylium-based route to conjugated dienynes: The first synthesis of carduusyne A",,10.1016/0040-4039(96)00153-0,1996-03-01,0.6979523627302945
Tetrahedron,A novel rearrangement of ketazine dianion: New synthetic route to pyrroles and tetrahydropyridazines,,10.1016/s0040-4039(00)93120-4,1976-10-01,0.6979519765810853
Journal of Organic Chemistry,"Practical Synthesis of BILA 2157 BS, a Potent and Orally Active Renin Inhibitor:  Use of an Enzyme-Catalyzed Hydrolysis for the Preparation of Homochiral Succinic Acid Derivatives","We have developed a highly convergent and stereoselective synthesis of BILA 2157 BS, a potent and orally active renin inhibitor. The synthesis proceeds in 15 distinct chemical steps (with several integrated, multistep operations) from aminodiol 4. The key step in the synthesis involves the use of an enantiospecific, enzyme-catalyzed hydrolysis of a substituted succinate diester to provide a homochiral succinic acid derivative in 98% enantiomeric excess (>/=2.5 kg scale). Recycling of the unwanted enantiomer is accomplished through base-catalyzed racemization, leading to an efficient deracemization of the starting racemic diester. The entire sequence proceeds without chromatographic purifications and delivers the product with >97% homogeneity. In addition, compared to the previously reported syntheses of BILA 2157 BS, this approach avoids the use of expensive chiral auxiliaries and cryogenics and, thus, should be amenable to the preparation of large quantities of this peptidomimetic inhibitor.",10.1021/jo990321x,1999-08-11,0.6979497760642382
European Journal of Organic Chemistry,Regioselective Oxidative Dehydrogenation under Nonenzymatic Conditions: A Synthetic Route to Gossypol,"Abstract A practical and scalable route was developed for the total synthesis of gossypol to allow for the construction of dozens of gossypol derivatives. t BuO 2 Ac was found to be a highly efficient oxidant for the polymerization of hemigossypol through a biosynthetic process under nonenzymatic conditions to give gossypol. Hemigossypol was synthesized on a gram scale by starting from commercially available carvacrol and dimethyl succinate and using a Stobbe condensation, an electrophilic cyclization, and the Michael addition of ortho ‐quinone methide as key steps.",10.1002/ejoc.201301126,2013-10-11,0.6978679009585125
Synlett,Asymmetric Strecker Route Toward the Synthesis of the Corey Intermediate of Lactacystin,All articles of this category An efficient synthesis of Corey's precursor ( 2 ) of lactacystin has been accomplished by the use of asymmetric Strecker synthesis of α-acyloxyketone 4 having l-Phe as a chirality transferring group. lactacystin - Corey's intermediate - asymmetric Strecker synthesis - α-acyloxyketone - amino nitrile,10.1055/s-2000-7948,2000-01-01,0.6978477295177713
Synlett,"Development of a Scalable Chiral Synthesis of MK-3281, an Inhibitor of the Hepatitis C Virus NS5B Polymerase",The development of a scalable chiral synthesis for the HCV NS5B inhibitor MK-3281 is being reported. Several alternative routes were explored and are being described.,10.1055/s-0030-1260790,2011-06-15,0.6978238590611411
Organic Process Research & Development,Development of Scalable Synthesis of Chiral Sultam via a Chiral Phosphoric Acid-Promoted <i>tert</i>-Butyl Carbamate Deprotection–Resolution Sequence or Diastereoselective Hydrogenation,"The discovery and process development for the synthesis of diastereopure sultam ( 1 ), a key chiral intermediate in route to a clinical candidate, are disclosed. Continuous route development to access ( 1 ) was required to satisfy both time and dynamic material needs during successive campaigns. Three distinct methods were developed to obtain diastereopure material. The first-generation process invoked time-intensive supercritical fluid chromatography (SFC) to access the diastereopure ( 2 ). Subsequent route development enabled a scalable, time-effective classical resolution approach that provided >20 kg of ( 1 ). Lastly, a Ruthenium-catalyzed diastereoselective hydrogenation approach was demonstrated on a hundred-gram scale and then coupled to the resolution technology to access ( 1 ), both reducing step count and improving overall yield relative to the resolution approach.",10.1021/acs.oprd.5c00263,2025-09-09,0.6977718405274681
Organic Process Research & Development,Development of a Scalable Process for an IL-17A Inhibitor LY3509754. Part II: Synthesis of the α-Bromoketone Intermediate Leveraging Concomitant Decarboxylation Following Enzymatic Ester Hydrolysis,"A route to the key α-bromoketone intermediate for the synthesis of an imidazo[1,2- b ]pyridazine IL-17A inhibitor via Horner–Wadsworth–Emmons condensation of commercially available 4,4-difluorocyclohexan-1-one ( 8 ) and methyl 2-(((benzyloxy)carbonyl)amino)-2-(dimethoxyphosphoryl)acetate ( 7 ) was developed and scaled up to support the production of drug substance for toxicology and clinical studies. The α,β-didehydroamino acid ester product 13 from Horner–Wadsworth–Emmons condensation was hydrolyzed under basic conditions to afford the corresponding N -protected α,β-didehydroamino acid 14, which was asymmetrically hydrogenated in the presence of the Ru- S -Xyl-Segphos dimer to afford the desired chiral amino acid 15 . After activation with carbonyl diimidazole, the resulting acyl imidazole was reacted with the magnesium ethyl malonate complex to afford a β-oxo ester 17, which was brominated followed by concomitant decarboxylation after enzymatic ester hydrolysis with Lipozyme TL IM to afford the desired α-bromoketone intermediate 5 . Stress tests and range-finding studies were carried out for all steps to support production. The optimized process was successfully scaled up to deliver 110 kg of α-bromoketone intermediate 5 to support the production of an IL-17A inhibitor. The overall yield of the optimized process was significantly improved to 46.5% from the 19.1% of the preclinical supplies process.",10.1021/acs.oprd.5c00004,2025-04-01,0.6976926145963274
Organic Process Research & Development,Development of a Scalable Route for a Highly Polar Heterocyclic Aminocyclopropyl Building Block,"A robust and scalable route toward key heterocyclic building block 1-(pyrimidin-2-yl)cyclopropan-1-amine hydrochloride from cyclopropanated starting material 1-amino-1-cyclopropanecarbonitrile hydrochloride was successfully developed. The key to success was the construction of a pyrimidine ring via cyclization from an amidine intermediate and a bench-stable 2-chloro vinamidinium hexafluorophosphate salt. The cyclization was performed under mild conditions, and the resulting 4-cloropyrimidine derivative was isolated in high yield and purity. The final hydrogenation was intensively optimized: A combination of Pd(OH) 2 /C as a catalyst and NaOMe as a base at 1 bar H 2 pressure in MeOH simultaneously cleaved the Cbz group and dechlorinated the pyrimidine ring while at the same time suppressing the over-reduction of the pyrimidine ring to below 1.0%. After acidification with HCl, followed by removal of the catalyst and NaCl by filtration, the final product was isolated in high yield and purity as a bench-stable off-white solid. The overall yield of the five-step sequence was 57%.",10.1021/acs.oprd.0c00358,2020-08-20,0.6976683582214285
Organic Process Research & Development,A Practical Synthesis of “Metabolite A<sub>1</sub>” (AAMU) of Caffeine,"A three-pot, preparative scale synthesis of 5-acetamido-6-amino-3-methyluracil, “metabolite A 1 ” (AAMU) ( 2 ) of caffeine, from readily available 6-aminouracil ( 3 ) in 72% overall yield is described.",10.1021/op960010d,1997-01-01,0.6976527204872514
Journal of Organic Chemistry,An Enantioselective Synthesis of Cis Perhydroisoquinoline LY235959,"A novel synthesis of NMDA receptor antagonist LY235959 (1) has been achieved in 13% overall yield and 17 steps from (R)-pantolactone (7). Highlights of the synthesis include (a) use of a chiral auxiliary controlled asymmetric Diels-Alder reaction to provide the desired absolute and relative stereochemistry at C-4a, C-6, and C-8a, (b) an efficient alkylation of hindered iodide 13 using a novel amide benzophenone imine, (c) oxidative ring opening of the [2.2.2] bicyclic system to simultaneously functionalize the molecule for intramolecular cyclization and phosphonate introduction, and (d) an increased understanding of how the C-3 stereochemistry may be controlled by thermodynamic equilibration. Synthesis of epimer 20 in high overall yield makes this synthetic route attractive for future development efforts.",10.1021/jo9717649,1998-01-22,0.6975864789729802
Synlett,"A Novel and Efficient Route for the Synthesis of Hydroxylated 2,3-Diarylxanthones","A novel, efficient and general route for the synthesis of hydroxylated 2,3-diarylxanthones is described. 3-Bromo-2-styrylchromone, the key intermediate of this synthesis, is obtained by a Baker-Venkataraman rearrangement of the appropriate 2′-cinnamoyloxyacetophenone, followed by a one-pot reaction with phen­yltrimethylammonium tribromide. The Heck reaction of these bromochromones with substituted styrenes gives methoxylated 2,3-diarylxanthones. The cleavage of the methyl groups with BBr3 gives the desired hydroxylated 2,3-diarylxanthones.",10.1055/s-2007-990900,2007-11-21,0.697584343600458
Organic Process Research & Development,Advancing Scalable Chemistry toward Novel CELMoDs: Process Development for the Synthesis of CC-90009,"CC-90009 ( 1 ) is a cereblon E3 ligase modulating drug (CELMoD) in clinical trials for the treatment of acute myeloid leukemia (AML). An efficient synthesis of 1 was required to support drug substance supply for clinical trials. The structure features an isoindolinone core, an α,α-difluorophenylacetamide, and a chemically sensitive α-amidoglutaramide moiety prone to hydrolysis or ring opening under basic or Lewis acidic conditions. A key feature of the synthesis was the transformation of a phthalide to the corresponding o -(chloromethyl)benzoate ester while managing the tendency of intermediates to relactonize. The realization of this transformation under mild conditions also serves as a model for a broadly applicable strategy to access these valuable motifs. Optimization of the nitrile hydrogenation and the amide bond formation to form 1 afforded the API in significantly improved yield and with high purity. This route was scaled up to supply early clinical trials and served as the basis for commercial route development.",10.1021/acs.oprd.2c00199,2022-09-01,0.697582165552504
Organic Process Research & Development,Process Development toward a Key Fragment of the PCSK9 Inhibitor Enlicitide Decanoate,"Here we report the development of a large-scale manufacturing process for the synthesis of the Northern Fragment of enlicitide decanoate (MK-0616), an orally bioavailable inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9). The key topics covered are (1) process development for the selective tryptophan allylation; (2) development of the one-pot process for two consecutive peptide coupling reactions; (3) process development for the one-pot cleavage of two N - tert -butyloxycarbonyl ( N -Boc) groups and a tert -butyl ester; and (4) process development of the magnesium chloride (MgCl 2 )-mediated selective macrolactamization. This optimized process was demonstrated to produce the key fragment at >150 kg scale per batch in the synthesis of enlicitide.",10.1021/acs.oprd.4c00504,2025-04-03,0.6975707767952949
Organic Process Research & Development,"Development of a Synthesis Process for a Novel HCV NS5A Inhibitor, Emitasvir","A new approach to the synthesis of Emitasvir (DAG181), a small molecule hepatitis C virus (HCV) nonstructural protein 5A (NS5A) inhibitor, is described. Enantioselective enzymatic desymmetrization with hydrolases in the synthetical approach can significantly avoid the loss of chiral raw materials in the resolution process. The synthesis route is further optimized and scaled-up to establish a new process that is applied to the preparation of kilogram scales of target active pharmaceutical ingredients (APIs). Compared with our initial process, the overall yield of target API was dramatically improved from 17 to 40%.",10.1021/acs.oprd.0c00519,2021-04-02,0.6975179845955642
Organic Process Research & Development,Process Development of an Efficient Kilogram-Scale Preparation of a Preferential Dopamine D<sub>3</sub> versus D<sub>2</sub> Receptor Antagonist SIPI 6398 as a New Antipsychotic Candidate,"Herein we describe the development of a kilogram-scale preparation of a preferential dopamine D 3 versus D 2 receptor antagonist SIPI 6398 ( 1 ) as a new alternative treatment for schizophrenia. Modification and optimization of the route includes one-pot synthesis of a trans / cis mixture of cyclohexyl ethyl acetate 19, direct crystallization of cyclohexyl acetic acid 21 in trans configuration, avoidance of hazardous reagents to obtain mesylate 24, and a salinization and recrystallization protocol to efficiently remove the olefinic impurity 31 from 12 (free base of 1 ). Ultimately these improvements led to the successful and facile preparation of 2.7 kg of SIPI 6398 in nine steps with an HPLC purity of >99.9%.",10.1021/acs.oprd.9b00182,2019-06-11,0.6975154928855185
Journal of Organic Chemistry,Synthesis of PDE IVb Inhibitors. 1. Asymmetric Synthesis and Stereochemical Assignment of (+)- and (−)-7-[3-(Cyclopentyloxy)-4-methoxyphenyl]hexahydro-3<i>H</i>-pyrrolizin-3-one,"Asymmetric synthesis of GlaxoSmithKline's highly potent phosphodiesterase inhibitor 1 has been accomplished in nine steps and 16% overall yield. The original strategy suggested involves as a key step the silylation of enantiopure six-membered cyclic nitronates 4 obtained by a highly stereoselective [4 + 2]-cycloaddition of an appropriate nitroalkene 5 to trans-1-phenyl-2-(vinyloxy)cyclohexane. Functionalization of the resulting 5,6-dihydro-4H-1,2-oxazine and subsequent stereoselective reduction of 1,2-oxazine ring in intermediate 2 furnished the pyrrolizidinone framework with the recovery of chiral auxiliary alcohol.",10.1021/jo201331h,2011-08-25,0.697450200311467
Tetrahedron,Practical synthesis of an orally active renin inhibitor aliskiren,,10.1016/j.tetlet.2005.07.028,2005-07-29,0.6974296053380881
Journal of Organic Chemistry,Concise Asymmetric Total Synthesis of Obolactone,The first efficient asymmetric synthesis of obolactone 1 has been accomplished in 11 steps and with a 15% overall yield in which Brown's enantioselective allylation reactions and ring-closing metathesis reaction are key steps.,10.1021/jo060028e,2006-03-10,0.6974175997658772
Tetrahedron,Synthetic vaccines: I. Synthesis of multivalent Tn antigen cluster-lysyllysine conjugates,,10.1016/s0040-4039(00)94669-0,1990-01-01,0.6974161131879251
Tetrahedron,Synthetic photochemistry. Synthesis of (±)oliveroline and (±)ushinsunine,,10.1016/s0040-4039(00)78675-8,1980-01-01,0.6974161131879251
Organic Letters,Scalable Formal Synthesis of (−)-Quinocarcin,"A scalable and unified strategy is described for the synthesis of (−)-quinocarcin, an important tetrahydroisoquinoline antitumor alkaloid. The strategy allows the practical formal synthesis of (−)-quinocarcin in 13 steps and 4.8% overall yield using N -phthaloyl- l -alanine as a chiral pool. It features the gram-scale and stereoselective synthesis of the tetrahydroisoquinoline moiety (AB ring) via Pd-catalyzed C(sp 3 )–H arylation and Pictet–Spengler condensation and a Cu(I)-catalyzed exo -selective [C + NC + CC] coupling reaction to generate the chiral pyrrolidine motif (D ring).",10.1021/acs.orglett.9b01511,2019-06-10,0.6972937020684314
Tetrahedron,The efficient synthesis of chiral key intermediates for monobactam antibiotics,,10.1016/s0040-4039(01)80020-4,1984-01-01,0.6972422678855829
Organic Process Research & Development,Practical Synthesis of A Benzophenone-Based NNRT Inhibitor of HIV-1,"A convergent synthesis of NNRTI 1 is described. The key step involves a direct coupling of acid chloride 4 with Grignard reagent 11 in the presence of bis[2-( N, N -dimethylamino)ethyl] ether that moderates the reactivity of the Grignard reagent to give benzophenone 7 . An efficient 2-step process for the preparation of 2-fluoro-3-methyl-4-aminobenzoic acid ( 3 ) is also described.",10.1021/op200301h,2012-03-07,0.6972373585208888
Journal of the American Chemical Society,Total Synthesis of (±)- and (−)-Actinophyllic Acid,"Development of efficient sequences for the total syntheses of (+/-)-actinophyllic acid (rac-1) and (-)-actinophyllic acid (1) are described. The central step in these syntheses is the aza-Cope/Mannich reaction, which constructs the previously unknown hexacyclic ring system of actinophyllic acid in one step from much simpler tetracyclic precursors. The tetracyclic hexahydro-1,5-methano-1H-azocino[4,3-b]indole ketone rac-37 is assembled from o-nitrophenylacetic acid in four steps, with oxidative cyclization of a dienolate derivative of tricyclic precursor rac-35 being the central step. In the first-generation synthesis, this intermediate is transformed in two steps to homoallyl amine rac-43, whose formaldiminium derivative undergoes efficient aza-Cope/Mannich reaction to give pentacyclic ketone rac-44. In four additional steps, this intermediate is advanced to (+/-)-actinophyllic acid. The synthesis is streamlined by elaborating ketone rac-37 to beta-hydroxyester intermediate rac-53, which is directly transformed to (+/-)-actinophyllic acid upon exposure to HCl and paraformaldehyde. This concise second-generation total synthesis of (+/-)-actinophyllic acid is realized in 22% overall yield from commercially available di-tert-butyl malonate and o-nitrophenylacetic acid by a sequence that proceeds by way of only six isolated intermediates. The first enantioselective total synthesis of (-)-actinophyllic acid (1) is accomplished by this direct sequence from tricyclic keto malonate (S)-35. Catalytic enantioselective reduction of alpha,beta-unsaturated ketone 66 is the key step in the preparation of intermediate (S)-35 from the commercially available Boc-amino acid 65. Discussed also is the possibility that the aza-Cope/Mannich reaction might be involved in the biosynthesis of (-)-actinophyllic acid.",10.1021/ja100178u,2010-03-10,0.6972164458022871
Angewandte Chemie International Edition,An Efficient Enantioselective Synthesis of (−)-Galanthamine,"An effective sequence: Palladium-catalyzed asymmetric allylic alkylation, Heck cyclization, and diastereoselective allylic oxidation were used in the total synthesis of (−)-galanthamine (3) in 14.8 % overall yield (from 1 and 2, Troc=2,2,2-trichloroethoxycarbonyl) and with 96 % ee. This improved procedure provides the shortest and most efficient nonbiomimetic synthesis of the acetylcholinesterase inhibitor.",10.1002/1521-3773(20020802)41:15<2795::aid-anie2795>3.0.co;2-2,2002-08-02,0.697174184442229
Journal of the American Chemical Society,"Enantioselective Total Syntheses of Allopumiliotoxins 267A, 323B‘, and 339A. Application of Iodide-Promoted Iminium Ion−Alkyne Cyclizations for Forming Allopumiliotoxin A Alkaloids","A concise, stereocontrolled strategy for the total synthesis of allopumiliotoxin A alkaloids is described. A much improved second generation total synthesis of enantiopure (+)-allopumiliotoxin 267A ( 3 ) was accomplished in 10 steps and 11% overall yield from the commercially available oxazolidinone precursor of alcohol 32 and 17 steps and 4% overall yield from N -[(benzyloxy)carbonyl]- l -proline. The first synthesis of (+)-allopumiliotoxin 323B‘ ( 4 ) rigorously confirms the complete stereostructure of 4 and establishes that the major C(15) epimer isolated from dendrobatid frogs has the 15 S configuration. The total synthesis of 4 was realized in 5 steps and 17% overall yield from alkyne 39 and aldehyde 20; the synthesis proceeded in 13 steps and 6% overall yield from ( S )-2-methyl-1-penten-3-ol and 17 steps and 3.5% overall yield from N -[(benzyloxy)carbonyl]- l -proline, the precursors, respectively, of alkyne 39 and pyrrolidine aldehyde 20 . The first total synthesis of allopumiliotoxin 339A ( 5 ) also confirmed the full stereostructure of this alkaloid. The synthesis of enantiopure 5 was achieved in 5 steps and 32% overall yield from alkyne 45 and pyrrolidine aldehyde 20; the synthesis proceeded in 17 steps and ∼7% overall yield from N -[(benzyloxy)carbonyl]- l -proline and 16 steps and ∼6% overall yield from the commercially available oxazolidinone precursor of 45 . These syntheses provide the best illustrations to date of the substantial utility of iodide-promoted iminium ion−alkyne cyclizations for constructing highly functionalized nitrogen heterocycles.",10.1021/ja961640y,1996-01-01,0.6971516604590808
Organic Letters,"Complementary Asymmetric Routes to (<i>R</i>)-2-(7-Hydroxy-2,3-dihydro-1<i>H</i>-pyrrolo[1,2-<i>a</i>]indol-1-yl)acetate","Two distinct and scalable enantioselective approaches to the tricyclic indole (R)-2-(7-hydroxy-2,3-dihydro-1H-pyrrolo[1,2-a]indol-1-yl)acetate, an important synthon for a preclinical S1P(1) receptor agonist, are reported. Route 1 employs a modified version of Smith's modular 2-substituted indole synthesis as the key transformation. Route 2 involves a highly enantioselective CuH-catalyzed 1,4-hydrosilylation as the stereodefining step. Both routes can be performed without chromatography to provide multigram quantities of the tricycle in ≥98% ee.",10.1021/ol303070k,2012-12-04,0.6971232419011504
Tetrahedron,A new and easier route to tetronic acid,,10.1016/s0040-4039(01)92328-7,1974-01-01,0.6970493631448332
Journal of Organic Chemistry,"General Approach to the Total Synthesis of 9-Methoxy-Substituted Indole Alkaloids: Synthesis of Mitragynine, as well as 9-Methoxygeissoschizol and 9-Methoxy-<i>N</i><sub>b</sub>-methylgeissoschizol","Herein, the full details of the synthesis of the 9-methoxy-substituted Corynanthe indole alkaloids mitragynine (1), 9-methoxygeissoschizol (3), and 9-methoxy-N(b)-methylgeissoschizol (4) are described. Initially, an efficient synthetic route to the optically active 4-methoxytryptophan ethyl ester 20 on a multigram scale was developed via a Mori-Ban-Hegedus indole synthesis. The ethyl ester of D-4-methoxytryptophan 20 was obtained with a radical-mediated regioselective bromination of indoline 12 serving as a key step. Alternatively, the key 4-methoxytryptophan intermediate 22 could be synthesized by the Larock heteroannulation of aryl iodide 10b with the internal alkyne 21a. The use of the Boc-protected aniline 10b was crucial to the success of this heteroannulation. The alpha,beta-unsaturated ester 6 was synthesized via the Pictet-Spengler reaction as the pivotal step. This was followed by a Ni(COD)(2)-mediated cyclization to set up the stereocenter at C-15. The benzyloxy group in 31 was removed to provide the intermediate ester 5. This chiral tetracyclic ester 5 was employed to accomplish the first total synthesis of 9-methoxygeissoschizol (3) and 9-methoxy-N(b)-methylgeissoschizol (4) as well as the opioid agonistic indole alkaloid mitragynine (1).",10.1021/jo801839t,2008-12-02,0.6970489244817277
Journal of the American Chemical Society,"Asymmetric, Stereocontrolled Total Synthesis of Paraherquamide A","The first total synthesis of paraherquamide A, a potent anthelmintic agent isolated from various Penicillium sp. with promising activity against drug-resistant intestinal parasites, is reported. Key steps in this asymmetric, stereocontrolled total synthesis include a new enantioselective synthesis of alpha-alkylated-beta-hydroxyproline derivatives to access the substituted proline nucleus and a highly diastereoselective intramolecular S(N)2' cyclization to generate the core bicyclo[2.2.2]diazaoctane ring system.",10.1021/ja036713+,2003-09-11,0.6970099926962636
Tetrahedron,"A new ready route to 1,4-ketoaldehydes and 1,4-diketones with application to the synthesis of z-jasmone and dihydrojasmone",,10.1016/0040-4039(88)85300-0,1988-01-01,0.6969766008282203
Organic Letters,1-Oxo-5-hydroxytryptamine:  A Surprisingly Potent Agonist of the 5-HT<sub>3</sub> (Serotonin) Receptor,"A novel synthetic route to 1-oxo-5-hydroxytryptamine, the benzofuran analogue of serotonin, has been developed. The new synthesis proceeds via the [3+2] cycloaddition of p-benzoquinone and 2,3-dihydrofuran, followed by a Lewis acid-catalyzed isomerization. This molecule proves to be a competent agonist (equipotent to serotonin) of the 5-HT3 receptor, demonstrating that the indolic proton of serotonin is not essential to its activation of the receptor.",10.1021/ol071083s,2007-07-18,0.696962994589546
Synthesis,"Second-Generation, Biomimetic Total Synthesis of Chaetominine","A straightforward total synthesis of the potent anticancer agent (–)-chaetominine is reported. Central to this synthesis was a biomimetic oxidative cyclization of a tryptophanyl-alanine dipeptide, which provided a fully elaborated 1,2,3,4-tetrahydropyrido[2,3-b]indole. Reduction of this intermediate followed by spontaneous cyclization and installation of the side chain provided synthetic chaetominine in a nine-step sequence in 14% overall yield starting from commercially available, inexpensive starting materials.",10.1055/s-0029-1216923,2009-07-30,0.6969306370342235
Organic Process Research & Development,The Development of a Manufacturing Route to an MCHr1 Antagonist,Process development work to provide an efficient manufacturing route to a MCHr1 antagonist is presented herewith. Features of this development work include a scalable manufacturing route to the useful 6-oxa-2-azaspiro[3.3]heptane building block and the use of a (soluble) alternative to sodium triacetoxyborohydride.,10.1021/acs.oprd.6b00006,2016-02-26,0.6968929097341305
Organic Process Research & Development,Lab-Scale Preparation of a Novel Carbocyclic Chemokine Receptor Antagonist,"The preparation of a novel chemokine receptor type 2 (CCR-2) antagonist is described on a 135 g scale. The synthesis of an all-carbon bicyclic core was accomplished using a radical cyclization strategy using chiral precursors, wherein elaboration led to N -Boc carboxylic acid in good yield. After amidation using a traditional coupling reaction, a reductive amination using enantiomerically enriched 3-methoxy-4-pyranone led to the final compound. Although several steps of the syntheses involved reagents that would not be preferred in process and chromatography was used to provide the free-base diastereomer of the final succinate salt, the overall route went through stable intermediates that could be used for future scale-up. This lab-scale synthesis struck a balance between a quick scale-up and a more thorough process review of all possible methods and routes.",10.1021/op500265z,2014-11-09,0.6968807444777367
Organic Letters,"Synthesis of 4-Azido-4-deoxy-Neu5,7,8,9Ac<sub>4</sub>2en1Me. A Key Intermediate for the Synthesis of GG167 from<scp>d</scp>-Glucono-δ-lactone","[reaction: see text] Stereoselective synthesis of 5-acetamido-7,8,9-tri-O-acetyl-2,6-anhydro-4-azido-3,4,5-trideoxy-D-glycero-D-galacto-non-2-enonic acid methyl ester, an advanced key intermediate for the synthesis of neuraminidase inhibitor GG167 (Zanamivir, Relenza), was accomplished using D-glucono-delta-lactone as starting material. A highly diastereoselective allyllation of an imine intermediate, a regioselective azide-opening of an aziridine, and chemoselective oxidations of vicinal diols served successfully as key steps.",10.1021/ol0491890,2004-05-27,0.6968276903397304
Synthesis,Total Synthesis of (+)-Pinellic Acid,"A straightforward strategy for the synthesis of (+)-pinellic acid in 16% overall yield and 13 steps, starting from (1 R )-1-(furan-2-yl)hexan-1-ol, is described. Key reactions in the synthesis include a Sharpless kinetic resolution, oxidation of a protected furan to reveal a but-2-ene-1,4-dione moiety, and an asymmetric reduction.",10.1055/s-0033-1338799,2013-05-17,0.6968275431443907
Journal of Organic Chemistry,"Efficient Synthesis of the Glucosidase Inhibitor Blintol, the Selenium Analogue of the Naturally Occurring Glycosidase Inhibitor Salacinol","An efficient synthesis of blintol, the selenium congener of the naturally occurring glycosidase inhibitor salacinol, and a potent glucosidase inhibitor itself, is described. Unlike our previously reported synthesis, this improved route makes use of p-methoxybenzyl ether protecting groups in the synthesis of one of the two key intermediates, 2,3,5-tri-O-p-methoxybenzyl-1,4-anhydro-4-seleno-D-arabinitol, from L-xylose. The other key intermediate, 2,4-O-benzylidene-L-erythritol-1,3-cyclic sulfate, was successfully prepared from D-glucose instead of the expensive L-glucose. All protecting groups in the resulting adducts were removed with trifluoroacetic acid to yield a mixture of stereoisomers, thereby obviating the problematic deprotection of benzyl ethers by hydrogenolysis. The major stereoisomer, blintol, was then obtained by fractional crystallization.",10.1021/jo048058+,2004-12-23,0.696805995448533
Tetrahedron,Photocyclization-fragmentation route to linear triquinanes: Stereocontrolled synthesis of (±)-endo-hirsutene,,10.1016/0040-4039(95)01445-n,1995-09-01,0.6967773152195137
Tetrahedron,Photocyclization-fragmentation route to linear triquinanes: stereocontrolled synthesis of (±)-endo-hirsutene,,10.1016/00404-0399(50)1445n-,1995-09-18,0.6967773152195137
Organic Process Research & Development,Synthesis of Rovafovir Etalafenamide (Part IV): Evolution of the Synthetic Process to the Fluorinated Nucleoside Fragment,"Fluorinated nucleoside 1 is a key starting material in the synthesis of rovafovir etalafenamide ( 2 ), a novel nucleotide reverse transcriptase inhibitor under development at Gilead Sciences for the treatment of HIV. While an initial manufacturing route enabled the production of 1 to support clinical development, alternative approaches were explored to further enhance manufacturing effectiveness, improve processing time, reduce cost, and minimize the environmental impact. Toward this end, two new routes were developed to a key synthetic intermediate, which was converted to 1 using a new protecting group strategy. The new chemistry led to improvements in the manufacturing process while reducing the overall process mass intensity (PMI).",10.1021/acs.oprd.1c00026,2021-05-07,0.6967293643370952
Tetrahedron,Formation of adenine from CH3COONH4/NH4HCO3—the probable prebiotic route for adenine,,10.1016/j.tetlet.2013.03.024,2013-03-13,0.696674149760706
Tetrahedron,"Enantioselective synthesis of the farnesyltransferase inhibitor, A-345665.0",,10.1016/j.tetlet.2006.10.008,2006-10-21,0.6966459022672574
Tetrahedron,An enantioselective formal synthesis of the proteasome inhibitor (+)-lactacystin,,10.1016/s0040-4039(02)01459-4,2002-09-01,0.6966459022672574
Journal of Organic Chemistry,Second-Generation Synthesis of (+)-Fastigiatine Inspired by Conformational Studies,"(+)-Fastigiatine is a complex alkaloid isolated from the alpine club moss Lycopodium fastigatum, most commonly found in New Zealand. It has been the subject of two successful synthetic campaigns. A second-generation route toward fastigiatine was developed to resolve two problematic steps from our initial synthesis. Selective reduction and protection of the C13 ketone improved the yield and reliability of the dibromocarbene ring expansion step. In the prior synthesis, cuprate addition to the C10 enone generated a 1:1 mixture of isomers in an advanced intermediate. Protection of the C13 alcohol with a large silyl group changed the conformational preference of the enone and led to a more selective conjugate addition to produce the desired β-epimer at C10. MacMillan's decarboxylative photoredox addition method proved to be more practical than the prior aminomethyl cuprate addition chemistry. The second-generation synthesis is longer than the original but improves the selectivity and reproducibility of the overall route.",10.1021/acs.joc.8b01144,2018-06-26,0.6966420510452987
Organic Letters,Catalytic Asymmetric Synthesis of an HIV Integrase Inhibitor,"An efficient synthesis of HIV integrase inhibitor (S)-(-)-1 via a unique asymmetric hydrogenation of a mixture of imines/enamine 5a-5b/5c is described. Hydrogenation of the imines/enamine by a Rh(I)-Josiphos complex afforded 6 in 90% yield and 90% ee. Amide formation completed the synthesis of 1 in 58% overall yield from 2, which is readily available from 3,4-dihydro-2H-pyran in a seven-step sequence. A deuterium labeling study suggests the asymmetric hydrogenation proceeds predominantly via the enamine tautomer.",10.1021/ol802604v,2008-12-19,0.6966260236385415
Tetrahedron,A novel asymmetric synthesis of axial-equatorial furofuran lignans: A synthesis of (+)-fargesin,,10.1016/0040-4039(95)01507-e,1995-10-01,0.6964442484797961
Synlett,Regio- and Enantioselective Alkylation of a N-Protected Pyrrolidin-3-one Using Enders’ Chiral Hydrazone Method: A Key Step Towards a New Asymmetric Total Synthesis of (-)-Quinocarcin and Related Analogues,The synthesis of C-4-alkylated pyrrolidin-3-one 5 was achieved by regio- and diastereoselective alkylation of chiral hydrazone 8 with electrophile 7 followed by selective deprotection. Highly functionalised compound 5 is the first key intermediate in our approach towards a new asymmetric total synthesis of (-)-quinocarcin (1) and related structural analogues 2 and 3.,10.1055/s-2002-34224,2002-01-01,0.6963999903621726
Synthesis,Shortened Synthesis of a Silicon-Stereogenic Cyclic Silane,The previous racemic synthesis of a six-membered ring silane from tert-butyltrichlorosilane required six steps (22% overall yield). A considerably shortened reaction sequence now allows for its preparation from rarely used tert-butylsilane in only two steps (42% overall yield). The new access also offers more facile purification of the intermediate(s) and the target compound.,10.1055/s-0030-1259989,2011-04-05,0.6963890688426365
Organic Process Research & Development,"Synthesis, Optimization, and Large-Scale Preparation of the Low-Dose Central Nervous System-Penetrant BACE1 Inhibitor LY3202626 via a [3 + 2] Nitrone Cycloaddition","Herein we report a summary of the synthetic development of LY3202626 from the initial discovery route to a final route that was scaled to make 150 kg. Key developments include the use of a [3 + 2] cyclization to set the cis ring junction of the formed isoxazoline, a one-pot thiazine formation, and three different ways to install the aniline: (1) Cu-catalyzed azide coupling and reduction, (2) nitration and reduction, and (3) Buchwald coupling with acetamide.",10.1021/acs.oprd.9b00471,2020-01-29,0.696264080503011
Journal of Organic Chemistry,Total Synthesis of Sphingofungin F Based on Chiral Tricyclic Iminolactone,"A new, efficient synthesis of sphingofungin F has been accomplished with 10.4% overall yield in 15 steps. The salient features of the synthesis are the utilization of methyl tricyclic iminolactone 3 for the asymmetric aldol reaction as a key step to introduce two desired stereogenic centers, one-pot reaction for the synthesis of omega-hydroxyketone from epsilon-caprolactone, and an effective one-step deprotection strategy to remove all protecting groups using 0.2 N HCl.",10.1021/jo100183d,2010-03-23,0.6962456750984509
Tetrahedron,"A novel, one-step annulation process for the synthesis of ring-fused 2-cyclopentenones",,10.1016/s0040-4039(00)96697-8,1987-01-01,0.6961337063628562
Organic Process Research & Development,An Improved Synthesis of Rimonabant: Anti-Obesity Drug,"A novel, cost-effective, and efficient process was developed for the large-scale synthesis of Rimonabant 1, an anti-obesity drug. The process involves the conversion of 4-chloro propiophenone 2 to cyclized acid 6 as a key intermediate that afforded Rimonabant 1 in good yield.",10.1021/op700110b,2007-07-27,0.6961118519239378
Organic Process Research & Development,Development and Scale-Up of an Improved Manufacturing Route to the ATR Inhibitor Ceralasertib,"Ceralasertib is currently being evaluated in multiple phase I/II clinical trials for the treatment of cancer. Its structure, comprising a pyrimidine core decorated with a chiral morpholine, a cyclopropyl sulfoximine and an azaindole, makes it a challenging molecule to synthesize on a large scale. Several features of the medicinal chemistry and early development route make it unsuitable for the long-term commercial manufacture of the active pharmaceutical ingredient. We describe the investigation and development of a new and improved route which introduces the cyclopropyl moiety in a novel process from methyl 2,4-dibromobutyrate. Following construction of the pyrimidine ring, large-scale chlorination with phosphoryl chloride was performed with a safe and robust work-up. An S N Ar reaction required an innovative work-up to remove the unwanted regio-isomer, and then a Baeyer–Villiger monooxygenase enzyme was used to enable asymmetric sulfur oxidation to a sulfoxide. A safe and scalable metal-free sulfoximine formation was developed, and then optimization of a Suzuki reaction enabled the manufacture of high-quality ceralasertib with excellent control of impurities and an overall yield of 16%.",10.1021/acs.oprd.0c00482,2020-12-15,0.6961111880298448
Organic Process Research & Development,Improved Synthesis of the Nav1.7 Inhibitor GDC-0276 via a Highly Regioselective S<sub>N</sub>Ar Reaction,"The development of a redesigned and improved second-generation synthesis of the Nav1.7 inhibitor GDC-0276 based on experience gained from a fit-for-purpose first-generation synthesis will be described. The first-generation synthesis proceeded via a regioselective S N Ar reaction on the advanced starting material t- butyl 5-chloro-2,4-difluorobenzoate with 1-adamantanemethanol. In the newly developed second-generation synthesis, the much improved regioselective S N Ar reaction was performed on the readily available starting material 1-chloro-2,4-difluorobenzene, followed by installation of the carboxylate group by electrophilic aromatic bromination and a palladium-catalyzed alkoxycarbonylation. A subsequent Suzuki–Miyaura cross-coupling reaction was then telescoped directly into a phase-transfer-catalyzed ester hydrolysis. Amidation of the resulting acid intermediate with 1-azetidine sulfamide in turn provided GDC-0276 in high overall yield and purity on a 100 kg scale.",10.1021/acs.oprd.9b00082,2019-07-31,0.6961005880022156
Organic Process Research & Development,Process Development and Scale Up of a Glycine Antagonist,"A synthetic route amenable to large-scale synthesis of the glycine antagonist (2 R,4 E )-7-chloro-4-(2-oxo-1-phenyl-pyyrrolidin-3-ylidene)-1,2,3,4-tetrahydroquinoline-2-carboxylic acid, (2 R,3 R,4 R,5 S )-6-(methylamino)hexane-1,2,3,4,5-penta-ol 12 is presented. The route consists of four stages of chemistry. Stage 1 starts from 5-chloro-2-iodoaniline hydrochloride and is a three-step telescoped stage consisting of an imine formation with ethyl glyoxalate, Mannich reaction using vinyloxytrimethylsilane, and subsequent Wittig reaction with (2-oxo-1-phenyl-3-pyrrolidinyl)triphenylphosphonium bromide. The stage 1 product (4 E )-2[(5-chloro-2-iodophenyl)amino]-4-(2-oxo-1-phenyl-pyrrolidin-3-ylidene)butanoic acid ethyl ester 17 is subjected to an enzyme-catalysed kinetic resolution to prepare the single (2 R )-enantiomer 19 as the ethyl ester. Stage 3 is the intramolecular Heck reaction to yield (2 R,4 E )-7-chloro-4-(2-oxo-1-phenyl-pyrrolidin-3-ylidene)-1,2,3,4-tetrahydroquinoline-2-carboxylic acid ethyl ester 31 . The final stage is ester saponification and meglumine salt formation to afford the drug candidate molecule 12 . In total, more than 300 kg of target 12 was produced with a purity >99.9%. Aspects of route selection as well as elements of process understanding and control are discussed.",10.1021/op9001824,2009-09-23,0.6960986283010103
Tetrahedron,Synthesis of 5-phenoxyisobenzofuran-1(3H)-one as a key intermedate of the drug roxadustat,,10.1016/j.tetlet.2020.152181,2020-07-05,0.6960916655704675
Organic Process Research & Development,"Development of a Practical Telescoped Process to Prepare (<i>P</i>)-7-(2-Amino-6-fluorophenyl)-4-hydroxy-6-(trifluoromethyl)pyrido[3,4-<i>d</i>]pyrimidin-8(7<i>H</i>)-one: a Key Intermediate of KRAS<sup>G12C</sup> Inhibitor GH35","GH35 is a potent irreversible covalent inhibitor of KRAS G12C that is currently undergoing phase I clinical trials for the treatment of patients with advanced solid tumors. Herein, we describe an efficient and cost-effective telescoped process to produce an atropisomeric intermediate, GH35-RSM, for the synthesis of GH35. Iterative optimization based on medicinal chemistry synthetic route resulted in significant improvement of several key reactions, such as two-step chiral resolution affording highly pure atropisomer ( P )-methyl 1-(2-fluoro-6-nitrophenyl)-2-oxo-6-(trifluoromethyl)-1,2-dihydropyridine-3-carboxylate (5- P ) in 99.9% e . e . and 35% yield and introduction of a nitrile group into ( P )-3-amino-1-(2-amino-6-fluorophenyl)-2-oxo-6-(trifluoromethyl)-1,2-dihydropyridine-4-carbonitrile (17) by use of an environment-friendly catalyst system identified by high throughput screening. The telescoped six-step process was robustly performed to provide hundreds of kilograms of GH35-RSM in plants to support clinical studies.",10.1021/acs.oprd.4c00279,2024-09-13,0.6960486088269281
Synthesis,Synthesis of<b> </b><b><i>N</i></b><sup>6</sup>-[<i>endo</i><b>-2′</b>-(<i>endo</i>-5<b>′</b>-Hydroxy)norbornyl]-8-(<i>N</i>-methylisopropylamino)-9-methyladenine (WRC-0571): A Potent and Selective Adenosine A1 Receptor Antagonist,"A new versatile synthesis of N 6-[endo-2′-(endo-5′-hydroxy)norbornyl]-8-(N-methylisopropylamino)-9-methyladenine (WRC-0571), a highly potent and selective antagonist for adenosine A1 receptor, is presented. The overall yield is 14%. The key step involved the stereoselective reduction of endo-2-(diphenylmethyl­amino)norbornan-5-one to generate the endo-5-hydroxy substituent using the Luche reagent (NaBH4-CeCl3) at -40 °C.",10.1055/s-2006-958939,2007-01-01,0.6959948703507411
Synthesis,"Scalable Synthesis of 3-Ethyl-4-methyl-1,5-dihydro-2H-pyrrol-2-one: An Important Building Block of the Antidiabetic Drug Glimepiride","A four-step, practical, and easily scalable synthesis of 3-ethyl-4-methyl-1,5-dihydro-2H-pyrrol-2-one, an important building block of the antidiabetic drug glimepiride, has been accomplished. Key features are the synthesis of 3-methyl-4-hydroxy-2-butenolide in water and triflic acid mediated N-benzyl lactam N-deprotection. The main advantages of this process are the scalable synthetic route and decreased number of reaction steps, which paves the way for the industrial-scale synthesis of 3-ethyl-4-methyl-1,5-dihydro-2H-pyrrol-2-one.",10.1055/s-0040-1707344,2020-08-04,0.6959651691722986
Tetrahedron,"A new route to β-keto-δ-lactones: Practical preparation of (R)-3-hexyl-5,6-dihydro-4-hydroxy-6-undecyl-2H-pyran-2-one, a key intermediate in the asymmetric synthesis of tetrahydrolipstatin",,10.1016/s0040-4039(00)60566-x,1993-01-01,0.6958873209915845
Organic Letters,Synthesis of Two Key Fragments of the Complex Polyhalogenated Marine Meroterpenoid Azamerone,"A concise route toward two advanced fragments in the context of the total synthesis of the unique natural product azamerone is reported. Key synthetic features include the enantioselective synthesis of an epoxysilane and its Lewis-acid-induced cyclization and the installation of the pyridazine ring via a formylation/condensation sequence. This route provides strategic insights into the chemistry of phthalazinediols, facilitating synthetic approaches toward this class of natural products.",10.1021/acs.orglett.9b00090,2019-01-25,0.6958507675249418
Organic Letters,Total Synthesis of (−)-Saliniketals A and B,"A stereocontrolled total synthesis of the orthinine decarboxylase inhibitors saliniketals A and B is described. Key features of the 17-step route include the use of two boron aldol/reduction sequences to control six of the nine stereocenters, an intramolecular Wacker-type cyclization to install the bicyclic acetal core, and a late-stage Stille coupling to append the requisite (2 Z,4 E)-dienamide.",10.1021/ol801148d,2008-06-26,0.69584483877727
Organic Letters,Enantioselective Approach to (−)-Hamigeran B and (−)-4-Bromohamigeran B via Catalytic Asymmetric Hydrogenation of Racemic Ketone To Assemble the Chiral Core Framework,"A new strategy featuring an iridium-catalyzed asymmetric hydrogenation of a racemic ketone via dynamic kinetic resolution to generate a cyclopentanol with three contiguous stereocenters and a SmI2-promoted pinacol coupling to install the six-membered ring with correct stereochemistry has been described for the enantioselective total synthesis of (-)-hamigeran B (19 steps, 10.6% overall yield) and (-)-4-bromohamigeran B (19 steps, 12.3% overall yield).",10.1021/acs.orglett.6b00369,2016-03-04,0.6958348430647893
Synthesis,Total Synthesis of (–)-Aristoquinoline via an Intramolecular Nitrilium Ion Cyclization,Abstract The enantioselective total synthesis of the alkaloid aristoquinoline has been achieved in seven steps and 26% overall yield. A new preparation of the useful synthetic building block (–)-α-terpinyl amine was also developed in order to avoid stoichiometric mercury reagents or azide-containing intermediates. Key steps in the optimized synthetic route include an intramolecular nitrilium ion cyclization to form the characteristic azabicyclo[3.3.1]nonane ring system and a dia­stereoselective reduction of the resulting imine mixture to afford the natural product. An isomer of aristoquinoline containing an exocyclic alkene was also obtained and found to exhibit unusual chromatographic and spectroscopic properties.,10.1055/s-0041-1737276,2021-11-22,0.6958186966497624
Synthesis,"A Novel Asymmetric Synthesis of cis-(3R,4R)-N-(tert-Butoxycarbonyl)-4-methyl-3-(methylamino)piperidine","cis-(3R,4R)-N-(tert-Butoxycarbonyl)-4-methyl-3-(meth­ylamino)piperidine, a key intermediate for the synthesis of CP-690550 (a potent protein kinase inhibitor), is prepared via an asymmetric approach starting from ethyl 1-benzyl-3-oxopiperidine-4-carboxylate hydrochloride in an overall yield of 49%. The mild conditions and high yields obtained during the synthesis suggest a potential industrial application for this route.",10.1055/s-0030-1259963,2011-03-22,0.6957749989053509
Journal of Organic Chemistry,"A New Strategy for the Construction of the Imidazo[1,5-<i>a</i>]quinoxalin-4-one Ring System and Its Application to the Efficient Synthesis of BMS-238497, a Novel and Potent Lck Inhibitor","A new efficient strategy was developed for the construction of the imidazo[1,5-a]quinoxalin-4-one ring system. The new method involves condensation of o-nitroaniline with glyoxylate in methanol followed by treatment of the resulting alpha-(o-nitroanilino)-alpha-methoxy acetate with tosylmethyl isocyanide (TosMIC) reagent to give 1-(o-nitrophenyl)imidazole-5-carboxylate. Reductive cyclization of the nitro imidazole carboxylate afforded imidazo[1,5-a]quinoxalin-4-one in three steps and 60% overall yield. The new method was successfully applied to the synthesis of BMS-238497, a novel and potent Lck inhibitor.",10.1021/jo0355348,2004-01-13,0.695649474935354
Synthesis,An Efficient Total Synthesis of (+)-Varitriol from d-Ribonolactone,"A short and efficient total synthesis of cytotoxic natural (+)-varitriol has been accomplished in eight steps from γ-d-ribonolactone and 2,3-dimethylanisole in 41% overall yield. The key features include a highly stereoselective introduction of methyl at a carbonyl group and installation of the side chain with the aromatic portion by Julia-Kocieński olefination at C5 of the starting carbon skeleton.",10.1055/s-0030-1258201,2010-08-09,0.6956157406580156
Tetrahedron,"Mono-6-( O -2,4,6-triisopropylbenzenesulfonyl)-γ-cyclodextrin, a novel intermediate for the synthesis of mono-functionalised γ-cyclodextrins",,10.1016/s0040-4039(01)01934-7,2001-12-01,0.6956125113674447
Journal of Organic Chemistry,Practical Asymmetric Synthesis of a γ-Secretase Inhibitor Exploiting Substrate-Controlled Intramolecular Nitrile Oxide−Olefin Cycloaddition,"A practical asymmetric synthesis of the gamma-secretase inhibitor (-)-1 is described. As the key transformation, a highly diastereoselective intramolecular nitrile oxide cycloaddition forms the hexahydrobenzisoxazole core of 3 in four operations. Other aspects of the route include a highly stereoselective reduction of an isoxazole to form a cis-gamma-amino alcohol, an efficient chemical resolution, a dianion cyclization to construct a sultam ring, and the alpha-alkylation of a sultam with excellent diastereoselectivity. In each instance, the relative stereochemistry was evolved by way of substrate-based induction with > or = 96% ds. Kilogram quantities of the targeted drug candidate (-)-1 were obtained, without recourse to chromatography, by way of 10 isolated intermediates and in 13% overall yield.",10.1021/jo060033i,2006-03-11,0.695611848680476
Organic Process Research & Development,Optimized Synthesis of Indole Carboxylate Metallo-β-Lactamase Inhibitor EBL-3183,"A new synthetic route for the preparation of the metallo-β-lactamase inhibitor pre-candidate EBL-3183 was developed and carried out on a kilogram scale. The described process starts from a commercially available indole-2-carboxylate and employs an Ellman auxiliary approach coupled with ruthenium-catalyzed stereoselective reduction for the introduction of chirality. The key spirocyclic cyclobutane motif was assembled utilizing an epoxide building block, which was conveniently obtained in diastereomerically pure form. The amount and quality of the prepared final target EBL-3183 were sufficient for the preclinical studies.",10.1021/acs.oprd.3c00002,2023-03-30,0.6955986543143964
Journal of Organic Chemistry,Synthesis of Hexacyclic Parnafungin A and C Models,"A convergent, practical route to unstable hexacyclic parnafungin A and C models has been developed. Two iodoxanthones were prepared in four or five steps (33-50% overall yield). Suzuki-Miyaura coupling of the iodoxanthones with excess readily available 3-carbomethoxy-2-nitrophenyl pinacol boronate afforded the hindered highly functionalized 2-arylxanthones (53-58%) in the first key step. In the second key step, zinc reduction gave benzisoxazolinones that were treated with MsCl and then base to generate the unstable hexacyclic parnafungin A (13% overall yield for 8 steps) and C (8% overall yield for 9 steps) models. Analogously to the parnafungins, hexacyclic parnafungin C model decomposes to a phenanthridine with a half-life of 2 d in CDCl(3).",10.1021/jo101826p,2010-11-02,0.6955837209066286
Organic Process Research & Development,A Practical Stereoselective Synthesis and Novel Cocrystallizations of an Amphiphatic SGLT-2 Inhibitor,"A practical synthesis of the SGLT-2 inhibitor β- C -aryl- d -glucoside ( 1 ) has been developed. The route employed 2,3,4,6-tetra- O -trimethlysilyl- d -glucano-1,5-lactone as the key chiral building block, prepared efficiently from the commercially available, inexpensive raw materials, d -gluconolactone and trimethylsilyl chloride. The salient step in the synthesis is the Lewis acid-mediated stereoselective reduction of a methyl C -aryl peracetylated glycoside using a silyl hydride to set the stereochemistry of the crucial anomeric chiral center. Several novel cocrystalline complexes of 1 with l -phenylalanine and l -proline were discovered. Single-crystal structures of these complexes and several synthetic intermediates have been determined. The l -phenylalanine complex was developed and used to purify and isolate the API. All steps were implemented at multikilogram scale.",10.1021/op200306q,2012-03-28,0.6955790295163565
Organic Letters,Synthesis of Paclitaxel. 2. Construction of the ABCD Ring and Formal Synthesis,"A formal synthesis of the antitumor diterpenoid paclitaxel (Taxol) is described. The ABC ring of paclitaxel, synthesized starting from 1,3-cyclohexanedione and tri-O-acetyl-d-glucal by SmI2-mediated cyclization as the key transformation, was successfully converted to Takahashi's tetracyclic oxetane intermediate. A double Chugaev reaction was employed for introduction of the strained bridgehead olefin, and stereoselective formation of the oxetane ring afforded the known synthetic intermediate, completing the formal synthesis of paclitaxel.",10.1021/acs.orglett.5b01174,2015-05-26,0.6955596124758756
Synthesis,A Practical Synthesis of the Ansa Chain of Benzenic Ansamycin Antibiotics: Total Synthesis of an Ansatrienol Derivative,"A practical and stereocontrolled synthetic approach towards the ansa chain of the benzenic ansamycins (mycotrienins) is described, which can be scaled up to multigram quantities. Key features of the synthesis are the formation of the Z-configured tri­substituted double bond by a one-pot esterification of allyl(diisopropoxy)borane and ring-closing metathesis, formation of the β-keto ester via ethyl diazoacetate addition to an aldehyde, and use of the Duthaler-Hafner acetate aldol reaction for the introduction of the stereocenter at C3. The practicality of this synthesis is demonstrated by the preparation of an ansatrienol derivative, representing­ a formal total synthesis of the ansatrienins.",10.1055/s-2006-958967,2007-01-01,0.6955049503201873
Organic Letters,Synthesis of a Human Urinary Metabolite of Prostaglandin D<sub>2</sub>,"A chemical synthesis of the major human metabolite of prostaglandin D 2, tricyclic-PGDM, is described. The synthetic route starts from iodocyclopentenone 1 (available from cyclopentadiene in 6 steps) and requires 13 synthetic transformations. The synthetic route takes advantage of a contrasteric allylation to establish the 1,2-cis relationship between the ring hydroxyl group and side chain. A second key sequence is the application of Fu’s copper-catalyzed C–H insertion of a diazoacetate followed by an alkyne semihydrogenation to introduce the unsaturated side chain.",10.1021/acs.orglett.9b03983,2019-12-04,0.6954928533969077
Synthesis,A Practical and Convenient Synthesis of the Protease Inhibitor Epibestatin,"A convenient synthesis of the protease inhibitor epibestatin, a useful component in protease inhibition cocktails for use in proteomics research, is described. The synthesis sequence consists of seven steps, starting from phenylacetaldehyde, yielding enantiopure epibestatin in 8% overall yield. A regioselective Mitsunobu­ transformation of a diol is the key step in the sequence.",10.1055/s-0029-1218771,2010-05-05,0.6954758636819625
Tetrahedron,A general and efficient route to enantioselective synthesis of pumiliotoxin A alkaloids via a common key intermediate,,10.1016/j.tetlet.2003.08.113,2003-10-01,0.6954505990680562
Journal of Organic Chemistry,Concise Modular Synthesis and NMR Structural Determination of Gallium Mycobactin T,"A modular synthesis of mycobactin T and its N -acetyl analogue is reported in a route that facilitates permutation of the lipid tails. A key feature is the generation of N(α)-Cbz-N(ε)-benzyloxy-N(ε)-Boc-lysine ( A4 ) with methyl(trifluoromethyl)dioxirane in 59% yield. Selective hydroxamate N -acylation was achieved with acyl fluorides, enabling installation of lipids tails in the final step. O -Benzyl-dehydrocobactin T ( B4 ) was prepared by modifying a known five-step sequence with an overall yield of 49%. 2-Hydroxyphenyl-4-carboxyloxazoline ( C3 ) was prepared from 2-hydroxybenzoic acid and l -serine methyl ester in three steps with an overall yield of 55%. Ester coupling of A4 and B4 with EDCI afforded MbI-1 in 73% yield. Catalytic hydrogenation with Pd/BaSO 4 and 50 psi of H 2 simultaneously effected alkene reduction and debenzylation to afford MbI-2 in 96% yield. Fragment C3 was converted into acyl fluoride C4, which coupled with MbI-2 to afford MbI-3 in 51% yield. Finally, Boc-removal with HCl/EtOAc and treatment of the resultant hydroxylamine with stearyl fluoride furnished mycobactin T in 65% yield. Overall, the yield is 4% over 14 steps. The gallium mycobactin T- N -acetyl derivative (GaMbT-NAc) structure was determined by 1 H NMR. The structure shows an octahedral Ga and two internal hydrogen bonds between peptidic N–Hs and two of the oxygen atoms coordinating Ga.",10.1021/acs.joc.1c01966,2021-10-26,0.6953960318448131
Journal of the American Chemical Society,"Stereocontrolled Synthesis of Dafachronic Acid A, the Ligand for the DAF-12 Nuclear Receptor of <i>Caenorhabditis elegans</i>","An efficient synthetic route to the DAF-12 nuclear receptor ligand of C. elegans, dafachronic acid, is described that starts with the abundant plant sterol β-stigmasterol and proceeds in 37% overall yield. The synthesis establishes the structure of this rare nematode hormone.",10.1021/ja074306i,2007-07-21,0.6953177752493438
European Journal of Organic Chemistry,Synthesis of Immucillins BCX‐1777 and BCX‐4430 from a Common Precursor,"Abstract A convergent route for the synthesis of BCX‐1777 and BCX‐4430 from a Boc‐protected 2‐pyrrolidinone, derived from 2,3,5‐tri‐ O ‐benzyl‐ d ‐ribonolactone, and a dihalogenated pyrrolopyrimidine as the key starting materials is reported. A chemoselective cross‐coupling was achieved from the two key starting materials in 79 % yield. Luche reduction and mesylation resulted in the stereoselective formation of an advanced intermediate in 77 % yield over two steps, which served as a precursor for synthesizing BCX‐1777 and BCX‐4430 in 38 % (over 10 steps) and 32 % (over 11 steps) overall yields, respectively, from 2,3,5‐tri‐ O ‐benzyl‐ d ‐ribonolactone.",10.1002/ejoc.202200428,2022-05-27,0.6952116792734632
Journal of Organic Chemistry,"Practical Partial Synthesis of Myriceric Acid A, an Endothelin Receptor Antagonist, from Oleanolic Acid","Myriceric acid A ( 1 ) is an oleanane triterpene that is a potent and specific endothelin A receptor antagonist. A practical procedure for large-scale synthesis of myriceric acid A ( 1 ) has been developed starting from oleanolic acid 4 . The conversion of oleanolic acid 4 to the key intermediate myricerone 3 was achieved in an efficient manner employing a photochemical reaction (the Barton reaction) of nitrite 7 . Our synthetic procedure alleviated several difficulties of the original Barton's procedure with regard to yields and large-scale operation. Myricerone 3 afforded Horner−Wadsworth−Emmons (HWE) type phosphonate 2 which has proved to be a versatile precursor of 1 . The preparation of phosphonate 2 on a scale of several hundred grams is described. The synthesis was completed by condensation of 2 with 3,4-bis[(diphenylmethyl)oxy]benzaldehyde ( 21 ), giving α,β-unsaturated ester 22, which was deprotected to afford 1 . The whole synthetic sequence is efficient (14 steps, 31% yield) and requires no chromatographic purification except to obtain the final product 1 .",10.1021/jo9615864,1997-02-01,0.695186470580398
Journal of Organic Chemistry,Total Synthesis of Macrocyclolipopeptide Dysoxylactam A,"A highly stereoselective total synthesis of potent multidrug-resistant reverser dysoxylactum A has been accomplished in the longest linear sequences of 20 steps with an overall 10.2% yield. The key steps of this synthesis included Brown's crotylation, Evans alkylation, the Carreira protocol to generate the stereogenic center, and Yamaguchi macrolactonization.",10.1021/acs.joc.3c02780,2024-03-01,0.6951602997333932
Tetrahedron,An enantioconvergent route to (−)-kainic acid,,10.1016/s0040-4039(96)02467-7,1997-02-01,0.6951307222041218
Journal of Organic Chemistry,"A Practical and Scaleable Synthesis of A-224817.0, a Novel Nonsteroidal Ligand for the Glucocorticoid Receptor","A practical and scaleable synthesis of a novel nonsteroidal ligand for the glucocorticoid receptor A-224817.0 1A is described. The synthesis proceeds in seven steps starting from 1,3-dimethoxybenzene. The biaryl intermediate 5 was prepared by an optimized high-yielding and high-throughput Negishi protocol. The quinoline core 8 was constructed by using a modified Skraup reaction. The final product was obtained by a direct allylation reaction of lactol 10 with allyltrimethylsilane. The process was accomplished efficiently to produce 1A in 25% overall yield and >99% purity with simple and practical isolation and purification procedures.",10.1021/jo0268613,2003-03-20,0.6950304957034488
Organic Letters,"Practical Asymmetric Synthesis of Amathaspiramides B, D, and F","The practical asymmetric synthesis of amathaspiramides B, D, and F has been accomplished by utilizing an aza-Barbier allylation as the key step to construct the common intermediate with two adjacent stereocenters. A kinetically controlled cyclization to build the challenging thermodynamically less stable 8R-hemiaminal moiety is also important in the synthesis of amathaspiramide D. The route is readily scalable, and gram quantity of the final product D has been prepared.",10.1021/acs.orglett.6b00588,2016-04-11,0.6949814593675727
Journal of Organic Chemistry,Diastereoselective Arylithium Addition to an α-Trifluoromethyl Imine. Practical Synthesis of a Potent Cathepsin K Inhibitor,"A practical, chromatography-free synthesis of potent cathepsin K inhibitor 1 is described. The addition of 4-bromophenyllithium to an alpha-trifluoromethylimine derived from commercially available (S)-leucinol was accomplished in a highly diastereoselective manner (97.6% de, 91% yield). Subsequent Suzuki cross-coupling afforded biaryl 7. Oxidation of the alcohol and sulfide functionalities led to the formation of carboxylic acid 8. Crystallization of 7 and acid 8 as its dicyclohexylamine salt gave excellent impurity rejection. The final amide coupling with commercially available aminoacetonitrile hydrochloride afforded 1 in excellent purity (99.6A% by HPLC, 100% de, <3 ppm Pd, W, Cr).",10.1021/jo052430j,2006-05-01,0.6949316608602899
Synthesis,A New Approach to the Synthesis of the Nonpeptide NOP Receptor Antagonist J-113397,"A new synthesis that eliminates the need for chromatographic separation in order to obtain multigram quantities of J-113397, a competitive antagonist of the N/OFQ-NOP receptor system, is reported. N-Benzyl protected 4-oxopiperidinecarboxylate was used as the starting material to obtain an N-benzyl intermediate that could be resolved at a relatively early stage in the synthesis. The crucial step in the synthesis was reduction of the double bond of the β-enaminoester functionality of 1-benzyl-4-(3-ethyl-2-oxo-2,3-dihydrobenzoimidazol-1-yl)-1,2,5,6-tetrahydropyridine-3-carboxylic acid methyl ester, since Pd/C reduction gave inseparable mixtures. It could be reduced and epimerized to the desired trans diastere­oisomer in a one-pot reaction by treatment with magnesium metal in methanol.",10.1055/s-2007-966037,2007-05-02,0.6949284806266544
Organic Process Research & Development,Large Scale Practical Synthesis of Enantiomerically Pure <i>cis</i>-4-Amino-3-fluoro-1-methylpiperidine via Rhodium-Catalyzed Asymmetric Hydrogenation of a Tetrasubstituted Fluoroalkene,"The development of multikilogram scale green and economical synthetic route of enantiomerically pure cis -4-amino-3-fluoro-1-methylpiperidine 1 is described. The synthesis features a highly regio-, chemo-, and enantioselective asymmetric hydrogenation of N -benzyl-4-(( tert -butoxycarbonyl)amino)-5-fluoro-tetrahydropyridinium chloride 3 . No purification or chiral enrichment is necessary due to the high selectivity resulting from proper selection of the catalyst system Rh(NBD) 2 (BF 4 ) and Walphos 003. The crude product N -benzylpiperidine 4 was carried directly to N -methylpiperidine utilizing a highly effective one-pot debenzylation and reductive amination protocol. The target compound 1·2HCl was prepared in 66–68% overall yield with >99% ee and >98.5% purity from available compound 3-fluoropyridin-4-amine 2 with a process mass intensity of 150.",10.1021/acs.oprd.0c00525,2021-02-10,0.6949245583073073
Organic Process Research & Development,"A Scalable Synthesis of MN-447, an Antagonist for Integrins α<sub>v</sub>β<sub>3</sub> and α<sub>IIb</sub>β<sub>3</sub>","(2 S )-Benzenesulfonylamino-3-[3-methoxy-4-{4-(1,4,5,6-tetrahydropyrimidin-2-ylamino)piperidin-1-yl}benzoylamino]propionic acid, MN-447, is a potent antagonist of the integrins α v β 3 and α IIb β 3 . Herein, we report a novel synthetic protocol that produces MN-447 in an overall yield of 45%. This protocol, when compared with the original synthetic route for MN-447, is more cost-effective, requires fewer steps, does not require chromatographic purification of intermediates and MN-447, and increases the overall yield by 35%. This report focuses on the synthetic strategies that were developed for this protocol. Now, the large quantities of MN-447 that are needed for preclinical and toxicological studies can be readily obtained.",10.1021/op800073z,2008-06-21,0.6949230448905556
Journal of Organic Chemistry,Stereoselective Synthesis of a MCHr1 Antagonist,"Melanin-concentrating hormone (MCH) is implicated in the feeding behavior in mammals affording a potential target to control overeating in people. Compound 1 (AMG 076) has been identified as a potent MCHr1 antagonist for the treatment of obesity. A synthesis suitable for the large-scale preparation of this lead candidate was developed to support preclinical studies. A Robinson annulation of benzylpiperidone and resolution of the desired enone from a mixture of the diastereomers afforded key intermediate 6 after a stereoselective hydrogenation. Subsequent Fischer indole synthesis with hydrazine 5 then provided the advanced intermediate, indole 2. Two complementary reductive amination strategies employing either aldehyde 3 or lactol 4 led to the synthesis of title compound 1.",10.1021/jo701894v,2007-11-13,0.6949207864805492
Organic Letters,A Practical Synthesis of (−)-Kainic Acid,A highly practical stereoselective total synthesis of (-)-kainic acid is described. This synthesis features the stereoselective alkylation of an iodolactone intermediate that was efficiently prepared from (+)-carvone and introduction of carboxylic acid by hydrolysis of a nitrile accompanied by epimerizaion. This synthetic route enabled us to obtain 14.6 g of (-)-kainic acid.,10.1021/ol200434a,2011-03-21,0.6949181251162041
Synthesis,A Practical Synthesis of (-)-Kainic Acid,A highly practical stereoselective total synthesis of (−)-kainic acid is described. This synthesis features the stereoselective alkylation of an iodolactone intermediate that was efficiently prepared from (+)-carvone and introduction of carboxylic acid by hydrolysis of a nitrile accompanied by epimerizaion. This synthetic route enabled us to obtain 14.6 g of (−)-kainic acid.,10.1055/s-0031-1289570,2011-10-20,0.6949181251162041
Organic Letters,Pictet−Spengler Based Synthesis of a Bisarylmaleimide Glycogen Synthase Kinase-3 Inhibitor,A practical synthesis of the glycogen synthase kinase-3 (GSK3) inhibitor bisarylmaleimide 1 has been accomplished employing Pictet-Spengler methodology to access the indole 7-position in preparing the benzodiazepine tricyclic fragment. A seven-step linear sequence that starts with commercially available 5-fluoroindole 7 affords the bisarylmaleimide 1 in 33% overall yield.,10.1021/ol101405g,2010-07-19,0.6948693692931276
Organic Process Research & Development,Process Development of the Synthetic Route to Sulamserod Hydrochloride,"Sulamserod hydrochloride is a potent 5-HT 4 receptor antagonist and was a clinical candidate for the treatment of gastrointestinal disorders. Process development of the fairly long synthetic route (12 linear, 14 overall steps) was undertaken. Process improvements were highlighted by aromatic chlorination choices in making dichlorobenzodioxan 2 and acetylaminochloroketone 7, a transfer hydrogenation reducing a nitro group and simultaneous aromatic dechlorination without ketone reduction to give aminoketone 5, and use of the potential mutagenic iodosulfonamide 14 to make quaternary salt 11 . The chemistry was scaled-up into pilot plant reactor vessels to produce multikilogram amounts of Sulamserod hydrochloride suitable for drug development.",10.1021/op0002040,2000-12-13,0.6947967412579568
Organic Process Research & Development,"Development of a Manufacturing Route to Avibactam, a β-Lactamase Inhibitor","Process development work to provide an efficient, robust, and cost-effective manufacturing route to avibactam, a β-lactamase inhibitor is presented herewith. Aspects of this optimization work include the counterintuitive introduction of a protecting group to effect a difficult urea formation and the use of controlled feed hydrogenation conditions to facilitate an elegant one pot debenzylation and sulfation reaction. Overall, the commercial process delivers avibactam in much improved yield with significant reduction in the environmental footprint.",10.1021/acs.oprd.6b00268,2016-09-14,0.6947566368006003
Journal of Organic Chemistry,Enantioselective Synthesis of (+)-Malbrancheamide B,"The asymmetric total synthesis of the chlorinated [2.2.2]-diazabicyclic indole alkaloid (+)-malbrancheamide B is reported. Key to the synthesis is a domino reaction sequence that employs an aldol condensation, alkene isomerization, and intramolecular Diels-Alder cycloaddition. Diastereofacial selection between the azadiene stereofaces is enforced with a chiral aminal auxiliary. A formal 7-step (longest linear route) synthesis of (±)-malbrancheamide B is also reported.",10.1021/jo3026059,2013-01-29,0.6946877036530639
Organic Letters,The First Total Synthesis of a Highly Branched Arabinofuranosyl Hexasaccharide Found at the Nonreducing Termini of Mycobacterial Arabinogalactan and Lipoarabinomannan,[reaction--see text] The first total synthesis of the arabinofuranosyl hexasaccharide present at the nonreducing termini of mycobacterial arabinogalactan and lipoarabinomannan is reported. The oligosaccharide was prepared as its methyl glycoside via a route that is both highly efficient and convergent. Addition of two beta-D-arabinofuranosyl residues simultaneously in high yield and with excellent stereocontrol was the key step of the synthesis.,10.1021/ol005907g,2000-04-21,0.694660954755924
Organic Process Research & Development,"Development of an Efficient, Scalable Route for the Preparation of a Novel Insulin-Like Growth Factor-1 Receptor Modulator","A chromatography-free and efficient synthesis of insulin-like growth factor-1 receptor (IGF-1R) modulator is reported. Herein we describe an improved synthesis for the target compound, which features facile introduction of a novel pyrrolidinyl-pyrimidyl isoxazole 8, via in situ sulfone displacement by fluorine. The overall process consists of six chemical steps and five isolations, with introduction of the expensive triheterocyclic unit 8 towards the end of the synthesis.",10.1021/op300120r,2012-07-20,0.6946594168143281
Tetrahedron,One-step synthesis of halfordinol,,10.1016/s0040-4039(01)97450-7,1971-01-01,0.6945660842367182
Tetrahedron,A two-step synthesis of 5-aminoisoxazoles from olefins,,10.1016/s0040-4039(01)88818-3,1969-01-01,0.6945660842367182
Synthesis,One-Step Synthesis of Drimenin and Cinnamolide,,10.1055/s-1970-21600,1970-01-01,0.6945660842367182
Tetrahedron,A two-step synthesis of the pyrono-quinonoid system,,10.1016/s0040-4039(00)70329-7,1967-01-01,0.6945660842367182
Synthesis,"A One-Step Synthesis of γ,δ-Unsaturated β-Ketoesters",,10.1055/s-1978-24692,1978-01-01,0.6945660842367182
Synthesis,"On the One Step-Synthesis of Perchloro-(3,4-dimethylenecyclobutene)",,10.1055/s-1975-23857,1975-01-01,0.6945660842367182
Synthesis,"A One-Step Synthesis of 2-Alkoxy-1,3-benzodithioles",,10.1055/s-1975-23654,1975-01-01,0.6945660842367182
Tetrahedron,"One-step synthesis of [1]benzothieno[3,2-b][1]benzothiophene from o-chlorobenzaldehyde",,10.1016/j.tetlet.2010.11.021,2010-11-12,0.6945660842367182
Tetrahedron,A three step synthesis of exaltolide and phoracantholide I,,10.1016/s0040-4039(00)84531-1,1986-01-01,0.6945660842367182
Tetrahedron,One step synthesis of α-amido-β-lactams,,10.1016/s0040-4039(01)96190-8,1973-01-01,0.6945660842367182
Tetrahedron,A five-step formal synthesis of (−)-Jaspine B,,10.1016/j.tetlet.2011.09.045,2011-09-17,0.6945660842367182
Tetrahedron,A two-step biomimetic synthesis of antimalarial robustadials A and B,,10.1016/j.tetlet.2006.07.113,2006-08-15,0.6945660842367182
Tetrahedron,A two-step synthesis of terbinafine,,10.1016/0040-4039(95)02095-0,1996-01-01,0.6945660842367182
Tetrahedron,Cationic heterocyclization One step synthesis of condensed heterocyclics,,10.1016/s0040-4039(01)92088-x,1974-01-01,0.6945660842367182
Tetrahedron,One-step biomimetic synthesis of (±)-linderaspirone A and (±)-bi-linderone,,10.1016/j.tetlet.2011.03.081,2011-04-15,0.6945660842367182
Tetrahedron,"Two-step synthesis of (±)-stigmolone, the pheromone of Stigmatella aurantiaca",,10.1016/s0040-4039(01)00564-0,2001-05-01,0.6945660842367182
Tetrahedron,A one-step synthesis of thiiranes from ketohydrazones.,,10.1016/s0040-4039(01)83989-7,1965-01-01,0.6945660842367182
Tetrahedron,A one-step synthesis of 2-phenylthio-2-buten-4-olides.,,10.1016/s0040-4039(00)87655-8,1982-01-01,0.6945660842367182
Tetrahedron,Three-step synthesis of oxylipins from D. loretense,,10.1016/j.tetlet.2019.06.040,2019-06-22,0.6945660842367182
Tetrahedron,A one-step synthesis of γ-pyrones,,10.1016/s0040-4039(00)78603-5,1980-01-01,0.6945660842367182
Tetrahedron,A one step synthesis of Flindersine,,10.1016/s0040-4039(01)84261-1,1972-01-01,0.6945660842367182
Tetrahedron,"A one step synthesis of 1-alkylpyrazolo[5,4-d]pyrimidines",,10.1016/j.tetlet.2008.10.065,2008-10-19,0.6945660842367182
Tetrahedron,A two step synthesis of spiroketals,,10.1016/0040-4039(88)85054-8,1988-01-01,0.6945660842367182
Synthesis,A One-Step Synthesis of Functionalised Indenes,,10.1055/s-1981-29397,1981-01-01,0.6945660842367182
Tetrahedron,A one-step synthesis of cyclodextrin monoaldehydes,,10.1016/0040-4039(95)01808-u,1995-11-01,0.6945660842367182
Tetrahedron,One-step synthesis of isocorroles,,10.1016/j.tetlet.2007.10.033,2007-10-30,0.6945660842367182
Tetrahedron,"A one-step synthesis of azeto(3,2-d)isoxazoline",,10.1016/s0040-4039(00)93794-8,1976-05-01,0.6945660842367182
Tetrahedron,One-step synthesis of 4(3H)-quinazolinones,,10.1016/s0040-4039(01)00096-x,2001-03-01,0.6945660842367182
Tetrahedron,"A four step synthesis from α-pinene of 7,7-dimethylbicyclo[4.1.1]octa-2,4-diene",,10.1016/s0040-4039(00)92564-4,1976-11-01,0.6945660842367182
Tetrahedron,Four step synthesis of a 5′-deoxy-5′-iodomethylthymidine,,10.1016/0040-4039(96)00090-1,1996-03-01,0.6945660842367182
Journal of Organic Chemistry,Enantioselective Total Synthesis of FR900482,"The development of two approaches for the enantioselective total synthesis of FR900482 is described. A precursor for the formation of the benzazocine ring was assembled effectively by a modification of the Sonogashira coupling of an aryl triflate with a chiral acetylene unit derived from tartaric acid and the subsequent novel ketone formation via conjugate addition of pyrrolidine to the o-nitrophenylacetylene derivative. The first-generation approach to the key pentacyclic intermediate of our racemic total synthesis utilizes an intramolecular Mitsunobu reaction of an omega-hydroxynitrobenzenesulfonamide to form the benzazocine ring and a stepwise sequence to construct the hydroxymethyl group at the C(7) position. The key intermediate could be synthesized in optically pure form via formation of the characteristic hydroxylamine hemiacetal and a stereoselective epoxide formation. In the second-generation approach, the N-hydroxybenzazocine ring could be constructed directly from an omega-formylnitrobenzene derivative by intramolecular reductive hydroxylamination. The crucial stereoselective hydroxymethylation and the formation of the hydroxylamine hemiacetal could be performed efficiently by a one-pot sequence. After leading to the pentacyclic key intermediate, the total synthesis of (+)-FR900482 was accomplished by a modification of our protocol established in the racemic total synthesis. Stereochemical issues involved in the hydroxymethylation at the C(7) position and formation of the hydroxylamine hemiacetal are also discussed in detail.",10.1021/jo049862z,2004-03-20,0.6945532188040838
Journal of the American Chemical Society,Total Synthesis of (−)-Laulimalide,"(-)-Laulimalide (1), a structurally novel macrolide isolated in trace amounts from marine sponges, promotes abnormal tubulin polymerization and apoptosis in vitro, with a similar mode of action to that of Taxol(R), but with potentially less susceptibility to multidrug resistance. Herein, a flexible and convergent asymmetric synthesis of (-)-laulimalide is described. This synthesis featured a highly diastereoselective Sakurai reaction of 2 with 3 and a regioselective macrolactonization of an unprotected vicinal diol. Laulimalide was synthesized in 25 steps (longest linear; 36 overall) in 3.5% overall yield, providing a uniquely short and efficient route to 1 and its analogues.",10.1021/ja0258428,2002-04-17,0.6945116777676409
Synthesis,A Short and Efficient Synthesis of a Chiral Pyridazinone Derivative by the Chiral-Pool Method,"The asymmetric synthesis of a (R)-4,5-dihydro-5-methylpyridazin-3(2H)-one derivative bearing a pyrazolopyridine ring, which is a potent inhibitor of phosphodiesterase, was achieved with a high optical yield in four steps starting from (R)-2-chloropropionyl chloride by a chiral-pool method.",10.1055/s-2004-829107,2004-06-23,0.6944365534851623
Journal of Organic Chemistry,Total Synthesis of (−)-Reserpine Using the Chiron Approach,A highly stereocontrolled synthesis of ring D/E precursor to reserpine has been developed starting from (-)-quinic acid as a chiral template. The total synthesis of (-)-reserpine is described through the cyclization of an immonium lactam intermediate.,10.1021/jo961713w,1997-02-01,0.6944129915942335
Organic Process Research & Development,Practical Synthetic Method for the Preparation of Pyrone Diesters: An Efficient Synthetic Route for the Synthesis of Dolutegravir Sodium,A highly efficient and practical synthetic method for the preparation of pyrone diesters was established. The pyrone diester 3c can be prepared from readily available starting materials on a multihundred gram scale. The pyrone diester 3c can easily be converted to dolutegravir sodium ( 1 ). The synthetic route demonstrated herein provides an efficient and atom-economical synthetic method for preparing this potent anti-HIV agent.,10.1021/acs.oprd.8b00410,2019-03-12,0.6943737560101382
European Journal of Organic Chemistry,Using a Johnson‐Claisen Rearrangement Strategy to Construct Azaindoles – A Streamlined and Concise Route for the Commercial Process of Fevipiprant,"Abstract A novel and concise synthesis of the DP2 receptor antagonist Fevipiprant (NVP‐QAW039) was developed. The initial research route was suffering from a long reaction sequence to the functionalized 7‐aza‐indole core followed by a poorly selective N (1)‐alkylation with the benzyl side chain. These limitations were overcome by introducing the side chain early by reductive amination between the functionalized aldehyde and 2‐amino‐3‐bromopyridine. The Sonogashira coupling with prop‐2‐yn‐1‐ol introduces the 3 missing carbon atoms to build the 7‐aza‐indole core and sets the stage for the innovative Johnson‐Claisen key step. The reaction of the advanced propargylic alcohol derivative with trimethyl orthoacetate led to a reactive allene intermediate which spontaneously and selectively cyclizes to the 7‐aza‐indole QAW039‐methyl ester. QAW039 was isolated after ester saponification. Selectivity, yield, and ecological footprint of the new synthesis were significantly improved, and scalability was demonstrated.",10.1002/ejoc.202100686,2021-08-18,0.6943513195926606
Journal of Organic Chemistry,A Convenient Synthesis of a Selective Gelatinase Inhibitor as an Antimetastatic Agent,"Compound 1, 2-(4-phenoxyphenylsulfonylmethyl)thiirane, is a potent and selective inhibitor for human gelatinases (J. Am. Chem. Soc. 2000, 122, 6799-6800), enzymes implicated in a number of diseases, including cancer. This compound is showing excellent promise in animal trials in a number of disease models. Large quantities of this compound were necessary for these studies. A convenient four-step synthetic route for compound 1 is described herein. The synthesis is amenable to scale-up to tens of grams and gives an overall yield of 57% for this important compound.",10.1021/jo049857v,2004-04-16,0.6943438065600711
Organic Letters,A New and Efficient Strategy for the Synthesis of Podophyllotoxin and Its Analogues,[structure: see text]. An efficient and stereoselective strategy for the total synthesis of podophyllotoxin was developed. This route leads to podophyllotoxin 1 in only 12 steps with 29% overall yield. A notable feature of this synthetic strategy is the use of the cascade addition-alkylation to ensure the key C1-C2 stereochemistry that is pivotal for the synthesis of podophyllotoxin.,10.1021/ol0630954,2007-02-28,0.6943168841924834
Angewandte Chemie International Edition,Asymmetric Total Synthesis of Pinnaic Acid,"Pinned together: Asymmetric total synthesis of pinnaic acid was accomplished through a stereospecific route that features as key steps a Pd-catalyzed trimethylenemethane (TMM) [3+2] cyclization, a four-step tandem hydrogenation–cyclization, and cross-olefin-metathesis reactions (see scheme).",10.1002/anie.200701581,2007-06-25,0.6942953163498709
Organic Process Research & Development,Development of a Scaleable Synthesis of a Geminal Dimethyl Tertiary Amine as an Inhaled Muscarinic Antagonist for the Treatment of COPD,"An efficient and scalable process for the synthesis of muscarinic antagonist, PF-3635659 1, is described, illustrating redesign of an analogue-targeted synthesis which contained a scale-limiting rhodium-activated C–H amination step. The final route includes a reproducible modified Bouveault reaction which has not previously been reported on a substrate of this complexity, or on such a scale with over 5 kg of the requisite gem -dimethylamine prepared via this methodology.",10.1021/op200233r,2012-01-06,0.6941870607519645
Organic Process Research & Development,Use of Phosphazene Base BTPP for Phosphorylative Activation in the Scale-Up of BET Inhibitor GSK525762,"In this article, an improved synthesis of a key triazole intermediate in the synthesis of bromo- and extra-terminal domain (BET) inhibitor GSK525762 ( 1 ) is described, which avoids the need for the formation of a thioamide intermediate for the key methyltriazolo[1,4]benzodiazapine formation. Conditions for a phosphorylative activation of lactam 4 were identified through the extensive screening of reagents and solvents, where a number of phosphazene bases were found to have unmatched activity. Development efforts focused on the use of phosphazene base P1- t -Bu-tris(tetramethylene) (BTPP) with diethyl chlorophosphoridate (DECP) and culminated in the demonstration of the new process at a 750 g scale. The resulting synthetic route avoids the use of thiolating agent P 2 S 5 and isolation of the resulting thioamide while delivering 1 in exceptional purity with a reduced number of steps, resulting in a higher yield and improved throughput over the previous process.",10.1021/acs.oprd.2c00048,2022-08-18,0.6941835762849502
Journal of Organic Chemistry,Characterization and Synthesis of a 6-Substituted Benzo[<i>b</i>]thiophene,"An impurity observed during the synthesis of zileuton (Zyflo) has been isolated and characterized as a benzo[b]thiophene derivative that has undergone electrophilic substitution in the 6 position (4). A nine-step synthesis confirms the structural assignment. Key steps in the synthesis include a regioselective Friedel-Crafts coupling between 2-hydroxythioanisole, 8, and 1-(benzo[b]thien-2-yl)ethanol, 1, and formation of a benzo[b]thiophene from an o-methylthiobenzaldehyde, 14, and chloroacetone. The synthesis provides a potentially general route to substituted benzo[b]thiophenes.",10.1021/jo980537j,1998-07-30,0.6941186018644694
Journal of Organic Chemistry,Absolute Configuration of Key Intermediates and the Gram Scale Synthesis of Berotralstat and <i>ent-</i> Berotralstat,"Berotralstat (BCX-7353) is a potent plasma kallikrein inhibitor developed to prevent hereditary angioedema attacks. Initial racemic synthesis yielded limited quantities of the active ( R )-enantiomer. To support clinical studies, a stereoselective synthetic route was developed. Key intermediates were isolated, and their stereochemistry confirmed via X-ray diffraction. These efforts enabled the scalable preparation of 16 g of berotralstat in 61% yield and nearly 1 g of its enantiomer in 23% yield─representing the first reported gram-scale synthesis of both compounds.",10.1021/acs.joc.5c01685,2025-10-10,0.6941126974270928
Journal of Organic Chemistry,Large-Scale Asymmetric Synthesis of a Cathepsin S Inhibitor,"A potent reversible inhibitor of the cysteine protease cathepsin-S was prepared on large scale using a convergent synthetic route, free of chromatography and cryogenics. Late-stage peptide coupling of a chiral urea acid fragment with a functionalized aminonitrile was employed to prepare the target, using 2-hydroxypyridine as a robust, nonexplosive replacement for HOBT. The two key intermediates were prepared using a modified Strecker reaction for the aminonitrile and a phosphonation-olefination-rhodium-catalyzed asymmetric hydrogenation sequence for the urea. A palladium-catalyzed vinyl transfer coupled with a Claisen reaction was used to produce the aldehyde required for the side chain. Key scale up issues, safety calorimetry, and optimization of all steps for multikilogram production are discussed.",10.1021/jo9022809,2010-01-27,0.6940625394624967
Tetrahedron,The synthesis of potent thromboxane A2/ prostaglandin endoperoxide receptor antagonist,,10.1016/s0040-4039(01)80410-x,1989-01-01,0.6940405679493087
Organic Process Research & Development,An Efficient Synthesis of a Multipotent Eicosanoid Pathway Modulator,"An efficient, scalable synthesis of the multipotent eicosanoid pathway modulator 2-[3-[3[[5-ethyl-4′-fluoro-2-hydroxyl[1,1′-biphenyl]-4-yl]oxy]-propoxy]2-propoxylphenoxy]benzoic acid ( 1 ) is described. The process consists of nine chemical steps with the longest linear sequence having six isolations. Palladium metal-mediated cross-coupling assembles the biaryl fragment, and selective S N Ar chemistry is used to construct the resorcinol fragment. The synthesis converges at a phenolic coupling with an alkyl chloride to give the core structure of the active pharmaceutical ingredient (API). Further elaborations of the core and salt formation provides the final API. This process produced the drug candidate in 41% overall yield at multikilogram scale.",10.1021/op800257u,2009-01-22,0.6939897749986803
Organic Letters,Total Synthesis of 8-Deshydroxyajudazol B,"The total synthesis of a stereoisomer of 8-deshydroxyajudazol B (4), the putative biosynthetic intermediate of the ajudazols A (1) and B (2), is described. The key steps in the synthesis included an intramolecular Diels-Alder (IMDA) reaction to secure the isochromanone fragment, a novel selective acylation/O,N-shift to give a hydroxyamide which was cyclized to the oxazole and a high yielding Sonogashira coupling to form the C18-C19 bond. Partial alkyne reduction then afforded the target 4.",10.1021/ol200331u,2011-03-16,0.6939881306632899
Tetrahedron,An efficient route to 3-aminoindazoles and 3-amino-7-azaindazoles,,10.1016/j.tetlet.2008.05.100,2008-05-29,0.6938422978862249
Tetrahedron,The enantioselective synthesis of key intermediates for the synthesis of (+)-brevifloralactone from R-(−)-carvone,,10.1016/s0040-4039(01)00840-1,2001-07-01,0.6938248260195246
Journal of Organic Chemistry,Synthesis of a Tetrahydropyran NK<sub>1</sub> Receptor Antagonist via Asymmetric Conjugate Addition,"Two asymmetric syntheses of the NK(1) receptor antagonist 1-[2-(R)-{1-(R)-[3,5-bis(trifluoromethyl)phenyl]ethoxy}-3-(R)-(3,4-difluorophenyl)-4-(R)-tetrahydro-2H-pyran-4-ylmethyl]-3-(R)-methylpiperidine-3-carboxylic acid (1) were developed. In both routes, the core tetrahydropyran stereochemistry was established by asymmetric conjugate addition to an alpha,beta-unsaturated ester (6), using an amide of the chiral auxiliary pseudoephedrine. Selective ester reduction then allowed formation of lactone 2 with the thermodynamically preferred trans geometry. The chiral ether side chain (3) was attached by stereoselective acetal substitution. In the first route, the chiral piperidine ester fragment was installed at the end by N-alkylation. In the shorter second synthesis, this piece was appended to the Michael acceptor at the beginning.",10.1021/jo0504161,2005-04-29,0.6937873562171972
Organic Process Research & Development,Early Process Development of a Squaramide-Based CXCR2 Receptor Antagonist,"The synthesis of a CXCR2 antagonist is presented, highlighting the process changes made from research synthesis to clinical supply. The target compound is the choline salt of a nonsymmetrical squaramide, and the modifications to the synthetic route which have effect on chemical purity are discussed with reference to the isolated byproducts. Although drug substance quality was shown to increase following optimization of the linear sequence, an alternative one-pot, convergent sequence was introduced, which makes dual use of choline hydroxide as both base and salt-forming agent. The overall benefits of the strategic change is discussed in terms of overall yield and economy.",10.1021/acs.oprd.5b00072,2015-07-30,0.6937060385164203
Organic Process Research & Development,A Novel and Practical Synthesis of Mavorixafor,"A novel and practical synthesis of mavorixafor ( 1 ) is reported. The novelty of this synthetic route is the use of 8-chloro-5,6,7,8-tetrahydroquinoline ( 9 ) and 1,4-diaminobutane as the materials, instead of 8-amino-5,6,7,8-tetrahydroquinoline ( 4 ) and N,N-diprotected aminobutyraldehyde ( 6a or 6b ). The preparation of ( S )-8-(4-aminobutylamino)-5,6,7,8-tetrahydroquinoline ( 13 ) by resolution with N -acetyl- l -leucine was first achieved. Then the one-pot synthesis of 1 from 13 involving protection, condensation, and subsequent hydrolysis was successfully developed. In addition, the final product with a satisfactory purity (>99.5%, detected by both achiral and chiral HPLC) was obtained by a simple operation (salification) without column chromatographic purification.",10.1021/acs.oprd.2c00076,2022-06-09,0.6936964734776359
Organic Letters,Enantioselective Synthesis of Cephalimysins B and C,The first synthesis of cephalimysins B and C is reported. The route features a Ni(II)-diamine-catalyzed enantioselective conjugate addition of a densely substituted 3(2H)-furanone and an efficient dihydroxylation-lactonization sequence as key steps in the assembly of the spirocyclic core. The fully synthetic strategy is amenable to analog preparation.,10.1021/acs.orglett.6b03373,2017-02-03,0.6936911637763825
Synlett,Lateral Lithiation-Initiated Annulations in the Synthesis of 1-Oxygenated Carbazole Alkaloids and a Cycloheptacarbazole,"Anionic [4+2] annulation of lithiated furoindolones with dimethyl maleate followed by selective demethoxycarbonylation provides an efficient synthetic route to 3-methoxycarbonylcarbazoles. The route has led to the straightforward synthesis of two natural products, namely clausine E, mukonine, and their 4-prenyl analogues. A new route to cyclohepta[ d , e , f ]carbazole was also uncovered during the investigations.",10.1055/s-0031-1290380,2012-06-21,0.6936453935065485
Organic Process Research & Development,"Pilot-Scale Synthesis of a Novel Non-Xanthine Adenosine A<sub>1</sub> Receptor Antagonist. 1,3-Dipolar Cycloaddition of Pyridine <i>N</i>-Imine to an Acetylene","Adenosine A 1 receptor antagonist, FK838, has been synthesized in 44% overall yield by a five-step sequence which is operationally straightforward and readily carried out on a large scale. Investigations into the 1,3-dipolar cycloaddition process that afforded a pyrazolo[1,5- a ]pyridine derivative are also described. Process improvements and optimization of each step permitted elimination of column chromatography, resulting in a practical and cost-effective synthesis of FK838. These methods were successfully scaled up in a pharmaceutical pilot plant to give bulk drug used in clinical trials.",10.1021/op980039c,1998-08-05,0.6936072068758696
Synlett,Semi-Synthesis of (+)-Digitoxigenin: Selective Bromination for Construction of the Key Intermediate,"Abstract A concise and scalable semi-synthesis of (+)-digitoxigenin (1) has been accomplished in nine linear steps. This route features the construction of the C(15)=C(16) double bond in intermediate 6 via selective C16 bromination followed by elimination. Subsequesntly, a single-step SeO2 oxidation directly installed the C14-β-hydroxyl group, producing 7. This strategy avoids precious metals, greatly reduces synthesis costs, and can be extended to the synthesis of related cardiotonic steroids.",10.1055/a-2589-5573,2025-04-16,0.6935132346713889
Organic Process Research & Development,"A Scalable Synthesis of a 1,7-Naphthyridine Derivative, a PDE-4 Inhibitor","A six-step synthesis of a 4-[8-(3-fluorophenyl)[1,7]naphthyridin-6-yl]- trans -cyclohexanecarboxylic acid with an overall yield of 27% starting from 2-cyano-3-methylpyridine, cyclohexane-1,4-dicarboxylic acid dimethyl ester, and 3-fluorophenylboronic acid is described. The trans stereochemistry in the cyclohexane moiety was achieved through a series of equilibration steps at different stages of the synthesis.",10.1021/op100124x,2010-06-15,0.6935002467278669
Organic Process Research & Development,Process Development of a Tricyclic Diazepine-Based IDH1 Mutant Inhibitor,"Process development to improve synthetic access to a potent, selective, and brain-penetrant tricyclic diazepine clinical candidate that inhibits mutant IDH1 is described. A variety of disconnections were evaluated to determine the preferred sequence of fragment coupling. The optimized route involves a metal-catalyzed C–N coupling/reductive cascade to form the central diazepine core, improved entries to both the zigzag morpholine and cyclohexyl acid peripheral pieces, and an efficient end-game sequence of acylation, C–N coupling, and deprotection. In addition, a dynamic acylation process that enables selective acylation at N6 of an unprotected diazepine core is described.",10.1021/acs.oprd.4c00171,2024-06-06,0.693488361270817
Organic Process Research & Development,"The Development of a Manufacturing Route for the GPIIb/IIIa Receptor Antagonist SB-214857-A. Part 1:  Synthesis of the Key Intermediate 2,3,4,5-Tetrahydro-4-methyl-3-oxo-1<i>H</i>-1,4-benzodiazepine-2-acetic Acid Methyl Ester, SB-235349","The development of an efficient manufacturing route to 2,3,4,5-tetrahydro-4-methyl-3-oxo-1 H -1,4-benzodiazepine-2-acetic acid methyl ester SB-235349, a key intermediate in the synthesis of lotrafiban is described. The synthesis starts with 2-nitrobenzyl alcohol which is mesylated, reacted with methylamine and then dimethylacetylene dicarboxylate followed by reduction of the nitro group. Treatment of the resultant aniline with acid gives an intermediate quinazoline which rearranges on treatment with base to give a 1,4-benzodiazapine. Reduction of the exocyclic double bond affords SB-235349. The process can be run without isolation of any of the intermediates and has been used to prepare several tons of SB-235349.",10.1021/op034024c,2003-07-26,0.693370367875536
Tetrahedron,A new synthesis of the orally active renin inhibitor aliskiren,,10.1016/j.tetlet.2011.06.056,2011-06-26,0.6933388642247512
Tetrahedron,A formal total synthesis of the telomerase inhibitor dictyodendrin B,,10.1016/j.tetlet.2009.11.083,2009-11-27,0.6933110600643011
Tetrahedron,"Enantiospecific Total Synthesis of a β-Glucosidase Inhibitor, Cyclophellitol",,10.1016/s0040-4039(00)88756-0,1990-01-01,0.6933110600643011
Tetrahedron,"The first total synthesis of aplysamine 6, an inhibitor of isoprenylcysteine carboxy methyltransferase",,10.1016/j.tetlet.2008.10.103,2008-10-26,0.6933110600643011
Organic Process Research & Development,Convergent Synthesis of the Renin Inhibitor Aliskiren Based on C5–C6 Disconnection and CO<sub>2</sub>H–NH<sub>2</sub> Equivalence,"A novel synthesis of the renin inhibitor aliskiren based on an unprecedented disconnection between C5 and C6 was developed, in which the C5 carbon acts as a nucleophile and the amino group is introduced by a Curtius rearrangement, which follows a simultaneous stereocontrolled generation of the C4 and C5 stereogenic centers by an asymmetric hydrogenation. Operational simplicity, step economy, and a good overall yield makes this synthesis amenable to manufacture on scale.",10.1021/acs.oprd.5b00396,2016-01-05,0.6933110026053911
Journal of Organic Chemistry,"Practical Asymmetric Synthesis of Efavirenz (DMP 266), an HIV-1 Reverse Transcriptase Inhibitor","A highly enantioselective and practical synthesis of the HIV-1 reverse transcriptase inhibitor efavirenz ( 1 ) is described. The synthesis proceeds in 62% overall yield in seven steps from 4-chloroaniline ( 6 ) to give efavirenz ( 1 ) in excellent chemical and optical purity. A novel, enantioselective addition of Li-cyclopropyl acetylide ( 4a ) to p -methoxybenzyl-protected ketoaniline 3a mediated by (1 R,2 S )- N -pyrrolidinylnorephedrine lithium alkoxide ( 5a ) establishes the stereogenic center in the target with a remarkable level of stereocontrol.",10.1021/jo981170l,1998-10-21,0.6932230516747612
Tetrahedron,Scalable synthesis of cladosporin,,10.1016/j.tetlet.2019.02.012,2019-02-07,0.6932129046506372
Tetrahedron,"The first total synthesis of a bioxanthracene (−)-ES-242-4, an N-methyl-D-aspartate receptor antagonist",,10.1016/s0040-4039(98)00040-9,1998-03-01,0.6932100267612102
Organic Letters,<i>De Novo</i>Asymmetric Synthesis of Phoracantholide J,"A de novo asymmetric total synthesis of the macrolide natural product (S)-phoracantholide J has been achieved in 10 steps from the commodity chemicals (1-pentyne, ethyl acrylate, acetaldehyde, and hydrogen). The asymmetry of the route was introduced by a Noyori reduction of a 3-yn-2-one, which makes the route equally amenable to the synthesis of either enantiomer. In addition, this route relies upon an alkyne zipper, a hydroalkynylation, and a macrolactonization to complete the synthesis.",10.1021/acs.orglett.6b02432,2016-09-16,0.6931916891130507
Journal of Organic Chemistry,"Asymmetric Synthesis of a Potent, Aminopiperidine-Fused Imidazopyridine Dipeptidyl Peptidase IV Inhibitor","A practical asymmetric synthesis of a novel aminopiperidine-fused imidazopyridine dipeptidyl peptidase IV (DPP-4) inhibitor 1 has been developed. Application of a unique three-component cascade coupling with chiral nitro diester 7, which is easily accessed via a highly enantioselective Michael addition of dimethyl malonate to a nitrostyrene, allows for the assembly of the functionalized piperidinone skeleton in one pot. Through a base-catalyzed, dynamic crystallization-driven process, the cis-piperidionone 16a is epimerized to the desired trans isomer 16b, which is directly crystallized from the crude reaction stream in high yield and purity. Isomerization of the allylamide 16b in the presence of RhCl(3) is achieved without any epimerization of the acid/base labile stereogenic center adjacent to the nitro group on the piperidinone ring, while the undesired enamine intermediate is consumed to <0.5% by utilizing a trace amount of HCl generated from RhCl(3). The amino lactam 4, obtained through hydrogenation and hydrolysis, is isolated as its crystalline pTSA salt from the reaction solution directly, as such intramolecular transamidation has been dramatically suppressed via kinetic control. Finally, a Cu(I) catalyzed coupling-cyclization allows for the formation of the tricyclic structure of the potent DPP-4 inhibitor 1. The synthesis, which is suitable for large scale preparation, is accomplished in 23% overall yield.",10.1021/jo902573q,2010-02-03,0.6931721086060431
Synlett,A New Formal Synthetic Route to Entecavir,"We describe a new and straightforward approach to the formal synthesis of the hepatitis B virus inhibitor entecavir, an important hepatitis B drug, in ten steps overall. Key features of the route are a Morita–Baylis–Hillman reaction, a Sharpless asymmetric epoxidation, a reductive epoxide opening of an α,β-epoxy ketone, and a Riley selenium dioxide oxidation.",10.1055/s-0037-1612215,2019-03-06,0.6931068769758743
Tetrahedron,"Stereoselective total synthesis of (+)-mueggelone, a novel inhibitor of fish development",,10.1016/j.tetlet.2008.02.022,2008-02-12,0.6930846815178102
Tetrahedron,A new simple route for the synthesis of (±)-2-azetidinones starting from β-Enaminoketoesters,,10.1016/s0040-4039(99)01421-5,1999-09-01,0.6930466556988749
Journal of the American Chemical Society,"First Synthesis of Cytotoxic 8,9-Secokaurene Diterpenoids. An Enantioselective Route to (−)-<i>O</i>-Methylshikoccin and (+)-<i>O</i>-Methylepoxyshikoccin","A practical route for the total synthesis of 8,9-secokaurene diterpenes is described. The central step is the [3.3]sigmatropic rearrangement of spirocyclic intermediates such as 35, 40, and 41 . All three compounds must necessarily respond identically to properly install the absolute configuration of the bridgehead methine carbon. The total synthesis of (−)- O -methylshikoccin ( 2b ) was realized in 8% overall yield from the Wieland−Miescher ketone 9 . Its naturally occurring epoxide 47 was prepared with comparable efficiency. The preparative route developed herein should provide a general entry into this important class of diterpenoids.",10.1021/ja971527n,1997-10-01,0.6930358574416038
Angewandte Chemie International Edition,Total Synthesis of (−)-Strychnine via the Wieland-Gumlich Aldehyde,"Fifteen steps suffice for an enantioselective total synthesis of (-)-strychnine (1) from 1,3-cyclohexanedione. The key steps are the easy generation of the enantiopure intermediate 2, the closure of the piperidine ring by a reductive Heck reaction, and the elaboration of the indoline nucleus in an advanced synthetic stage. TBDMS=tert-butyldimethylsilyl.",10.1002/(sici)1521-3773(19990201)38:3<395::aid-anie395>3.0.co;2-5,1999-02-01,0.69303483153649
Organic Process Research & Development,Multigram Synthesis of Glyceollin I,Scaled-up procedures and preparation of glyceollin I in multigram quantities are described. The synthesis features construction of a cis-fused ring system in high enantiomeric excess after Sharpless asymmetric dihydroxylation of a key intermediate that is initially produced by an intramolecular Wittig reaction to afford the requisite alkene while simultaneously forming the first ring. The overall yield is 12% after 11 steps.,10.1021/op200112g,2011-06-23,0.6930133151659785
Synlett,Organocatalytic Synthesis of an Alkyltetrahydropyran,The first synthesis of an alkyltetrahydropyran using a diarylprolinol organocatalyst is described.,10.1055/s-0028-1087550,2009-01-21,0.6930048191863383
Tetrahedron,"A new synthetic route to 2-oxazolines. The electrochemical reduction of N-(2,2-dichloroethyl)amides as a key step",,10.1016/s0040-4039(97)10730-4,1998-02-01,0.6929311014768006
Organic Process Research & Development,Development of a Scalable Process for 1-β-Methyl Azetidinone: A Carbapenem Key Intermediate,"An optimized process for the stereoselective synthesis of 1-β-methyl carbapenem key intermediate (3 S,4 S )-[( R )-1‘-(( tert -butyldimethylsilyl)oxy)ethyl]-4-[( R )-1-carboxyethyl]-2-azetidinone ( 1 ) and (3 R,4 R )-4-acetoxy-3-[( R )-1‘-(( tert -butyldimethylsilyl)oxy)ethyl]-2-azetidinone has been developed employing commercially available chiral 4-phenyl-2-oxazolidinone. This method provides an efficient and cost-effective process with improved selectivity and higher yield.",10.1021/op0501085,2005-09-10,0.6929143100644767
Journal of the American Chemical Society,Divergent Enantioselective Synthesis of (−)-Galanthamine and (−)-Morphine,"An efficient divergent synthetic strategy for the synthesis of the opiate and amaryllidaceae alkaloids emerges by employing a Pd-catalyzed asymmetric allylic alkylation (AAA) to set the stereochemistry. Three generations of syntheses of galanthamine are discussed in detail with particular focus on the scope of the palladium-catalyzed AAA reactions and intramolecular Heck reactions. The pivotal tricyclic intermediate is available in six steps from 2-bromovanillin and the monoester of methyl 6-hydroxycyclohexene-1-carboxylate. This intermediate requires only two steps to convert to (-)-galanthamine. Using a Heck vinylation, we found that the fourth ring of codeine/morphine could be formed. The final ring formation involves a novel visible light-promoted hydroamination. Thus, six steps are required to convert the pivotal tricyclic intermediate into codeine, which has been demethylated in high yield to morphine.",10.1021/ja054449+,2005-09-24,0.6929088478519789
Tetrahedron,A novel synthetic approach to the cardiotoxin Batrachotoxin: An efficient synthesis of the AB ring system,,10.1016/s0040-4039(00)79312-9,1993-11-01,0.6928854308481839
Organic Letters,Asymmetric Total Synthesis of Eremophilanolide Sesquiterpene Xylareremophil and Its Congeners,"The first asymmetric, protecting group free total synthesis of eremophilanolide sesquiterpenes, xylareremophil ( 1 ), 2α,3α-epoxymairetolide A ( 2 ), and 2,3- seco -2,3-olide-1-deoxygenmairetolide F ( 3 ), is concisely achieved with a longest linear route of five to eight steps, starting from the known (5 S )-5,6-dimethyl-2-cyclohexenone as the chiral starting material. This synthetic approach mainly features an oxa-Pauson–Khand reaction of the highly functionalized chiral aldehyde precursor, forging a γ-butenolide-fused tricyclic core framework of eremophilanolides in a one-step manner. This study provides a novel strategic perspective for the divergent synthesis of the eremophilanolide sesquiterpenes.",10.1021/acs.orglett.5c00028,2025-02-24,0.6928781188416756
Organic Process Research & Development,Synthetic Process Development of BMS-599793 Including Azaindole Negishi Coupling on Kilogram Scale,"A new approach to the synthesis of 1 (DS003, BMS-599793), a small-molecule HIV entry inhibitor, is described. The initial medical chemistry route has been modified by rearranging the sequence of synthetic steps followed by replacement of the Suzuki coupling step by the Negishi conditions. Acylation of the resulting azaindole 7 under the Friedel–Crafts conditions is studied using monoesters of chlorooxalic acid in the presence of aluminum chloride. Polymorphism of 1 is also investigated to develop conditions suitable for preparation of the desired Form 1 of the target compound. The new route is further optimized and scaled up to establish a new process that is applied to the synthesis of kilogram quantites of the target active pharmaceutical ingredient.",10.1021/op400012p,2013-05-24,0.6928647709564583
Synlett,Semi-Synthesis of (+)-Digitoxigenin from Androstenedione,"Abstract An efficient stereoselective semi-synthesis of (+)-digitoxigenin has been achieved by a nine-step sequence with a 20.4% overall yield. The key features of the synthesis include a Saegusa–Ito oxidation reaction, a direct C14β-hydroxylation, and a Stille cross-coupling.",10.1055/a-2114-8823,2023-06-21,0.6928117644822792
Tetrahedron,"A new synthetic route to 1-chlorophenazines. The electrochemical monodechlorination of 3,3,6,6-tetrachloro-1,2-cyclohexanedione as a key step",,10.1016/s0040-4039(00)01097-2,2000-08-01,0.6927713380269476
Journal of Organic Chemistry,Organoboron-Based Allylation Approach to the Total Synthesis of the Medium-Ring Dilactone (+)-Antimycin A<sub>1b</sub>,"The stereoselective synthesis of (+)-antimycin A1b has been accomplished in 12 linear steps and 18% overall yield from (-)-ethyl lactate. A robust, scalable, and highly diastereoselective montmorillonite K10-promoted allylation reaction between an α-silyloxy aldehyde and a substituted potassium allyltrifluoroborate salt provides a general approach to the core stereochemical triad of the antimycin A family. The requisite (Z)-substituted potassium allyltrifluoroborate salt was synthesized using a syn-selective hydroboration/protodeboration of an alkynylboronate ester, followed by a Matteson homologation reaction. The total synthesis leverages an MNBA (Shiina's reagent)-mediated macrolactonization to generate the 9-membered dilactone ring and a late-stage PyBOP-mediated amide coupling employing an unprotected 3-formamidosalicylic acid fragment, thereby shortening the longest linear sequence and, perhaps most notably, generating the antimycin A C7-C8-C9 stereotriad in a single step using a single chiral pool-derived stereocenter.",10.1021/jo501134d,2014-07-14,0.6927070989198016
Organic Process Research & Development,Scalable Synthesis of the Desoxy-biphenomycin B Core,"We describe the evolution of a kilogram-scale synthesis of the protected cyclic tripeptide desoxy-biphenomycin B, based on an early discovery route. The retrosynthetic concept included a macrolactamization strategy to build the core ring system of biphenomycin B in combination with a double catalytic asymmetric hydrogenation protocol for the construction of the ansa -tripeptide precursor. Eventually, the kilogram process comprised a 16-step sequence with an overall yield for the longest linear sequence of 19.5%.",10.1021/op200207h,2011-09-13,0.692692990016181
Journal of Organic Chemistry,Thiopyran Route to Polypropionates:  An Efficient Synthesis of Serricornin,"The synthesis of serricornin [(4S,6S,7S)-7-hydroxy-4,6-dimethylnonan-3-one], a sex pheromone produced by the female cigarette beetle (Lasioderma serricorne F.), in seven steps from readily available racemic 1,4-dioxa-8-thiaspiro[4.5]decane-6-carboxaldehyde (6) is described. The key steps include enantioselective aldol reaction of 6 with tetrahydrothiopyran-4-one catalyzed by 5-[(2S)-pyrrolidine-2-yl]-1H-tetrazole to fabricate the tetrapropionate skeleton, stereoselective Li(s)Bu(3)BH reduction of the resulting aldol adduct, Barton-McCombie deoxygenation, and Raney nickel desulfurization.",10.1021/jo061747w,2006-10-14,0.6926774670647239
Organic Process Research & Development,"Development of an Efficient Scale-Up Synthesis Method for a β<sub>3</sub>-Adrenergic Receptor Agonist, Ritobegron Ethyl Hydrochloride","An efficient route for the multikilogram synthesis of a selective β 3 -adrenergic receptor agonist, ritobegron ethyl hydrochloride ( 1 ), was developed by changing the coupling method of 4-hydroxynorephedrine ( 2 ) with phenoxyacetate 3 . This new method successfully overcame several obstacles in the first-generation method via the use of aldehyde 3b derived from hemiacetal 10 to couple with 2 . The main advantages of the key intermediate 10 were that it was sufficiently stable to enable handling at large scales, it could be synthesized without an exothermic reaction or excessive use of expensive reagents, and it had the ability to reduce impurities by purification prior to coupling with 2 . The resulting second-generation method improved the overall yield from 27 to 43% and the purity from up to 98.5 to 99.5%. Furthermore, it was effective for 69 kg-scale synthesis, representing a major improvement over several hundreds grams scale of the first-generation method.",10.1021/acs.oprd.0c00278,2020-07-31,0.6926554984722544
Journal of the American Chemical Society,Design and Implementation of an Efficient Synthetic Approach to Furanosylated Indolocarbazoles:  Total Synthesis of (+)- and (−)-K252a,"The first total synthesis of the natural product (+)-K252a ( 2 ) has been achieved in 12 steps from commercially available materials, with a longest linear sequence of seven steps and an overall yield of 21%. The synthetic strategy employs novel rhodium carbenoid chemistry in the construction of both the indolocarbazole aglycon ( 4 ) and the carbohydrate moiety ( 9 ).",10.1021/ja9713035,1997-10-01,0.6926381042561933
Organic Letters,"Discovery and Process Synthesis of Novel 2,7-Pyrrolo[2,1-<i>f</i>][1,2,4]triazines","The synthesis of a new kinase inhibitor template 2-anilino-7-aryl-pyrrolo[2,1-f][1,2,4]triazine is described which includes a late stage orthogonally reactive key intermediate amenable to rapid diversification as well an optimized in situ triflate displacement to install the C2-aniline. Furthermore, an efficient scalable process approach will be highlighted which begins with tert-butyl carbazate to provide the key N-N bond and generates the pyrrolotriazine core through a stable bromoaldehyde intermediate followed by condensation with ammonium carbonate.",10.1021/ol2015237,2011-07-26,0.6926257838035453
Synthesis,An Efficient Synthesis of the Potent Dopamine D1 Agonist Dinapsoline by Construction and Selective Reduction of 2′-Azadimethoxybenzanthrone,"All articles of this category 8,9-Dihydroxy-2,3,7,11b-tetrahydro-1 H -naphth[1,2,3- de ]isoquinoline (dinapsoline, 1 ) is a potent dopamine D 1 receptor agonist with potential antiparkinsonian activity. A new synthesis was developed with the fully aromatic compound 2 as the key intermediate. The synthesis herein described is suitable for a larger scale preparation of dinapsoline compared to the previously known methods. Furthermore, the unproductive protection/deprotection step of the nitrogen is circumvented by maintaining a high oxidation state of the isoquinoline moiety throughout the synthesis. The construction of the framework was accomplished by Friedel-Crafts acylation and a Suzuki cross-coupling reaction between the commercially available 4-bromoisoquinoline and aryl boronic acid 5 , the latter demanding the transformation of the lithiation-directing amide back to a carboxylic acid functionality. The selective reduction was carried out stepwise with sodium borohydride and sodium cyanoborohydride. The new synthesis is highly yielding and reduces the number of transformations in the previously reported methods. regioselective reduction - boron - Suzuki cross-coupling - electrophilic aromatic substitution - acylation - hydrogenation - amide hydrolysis - cyclization",10.1055/s-2001-10809,2001-01-01,0.692543452178256
Organic Process Research & Development,An Improved and Scaleable Preparation of 7-Amino-3-vinylcephem-4-carboxylic acid,"A practical and efficient multikilogram-scale preparation of 7-amino-3-vinylcephem-4-carboxylic acid (7-AVCA), a key intermediate used in the synthesis of cefixime and cefdinir, is described utilizing p -methoxybenzyl 7-phenylacetamido-3-chloromethylcephem-4-carboxylate (GCLE) as a starting material. Reaction conditions were optimized to simplify the process, to improve the quality and to increase the yield. The process has been demonstrated on a multikilogram scale in 77% overall yield with a purity of >99%.",10.1021/op900053j,2009-07-02,0.6924665479217078
Organic Process Research & Development,An Improved and Practical Synthesis of Tranexamic Acid,"Tranexamic acid 1, a synthetic antifibrinolytic drug with the treatment being considered highly cost-effective in many countries, has been included in the WHO list of essential medicines. In this paper, we designed the synthesis of 1 via a novel seven-step route from the readily available starting material dimethyl terephthalate, performing with 99.6% purity in 59.2% overall yield. During the process, we successfully developed a direct and efficient method for the preparation of key intermediate methyl 4-(acetamidomethyl)benzoate by one-pot hydrogenation and acylation in acetic anhydride using Ni/Al 2 O 3 as a catalyst. More importantly, it should be a straightforward and practical way to circumvent the usage of toxic reagents (CrO 3, Cl 2 ), solvent (CCl 4 ), and expensive catalyst (PtO 2 ), etc., that plagued the previous methodologies.",10.1021/op500395b,2015-02-05,0.6924455833128902
Organic Process Research & Development,Development of a Fully Telescoped Synthesis of the S1P1 Agonist GSK1842799,"The development of a fully telescoped synthesis of the potent and selective S1P1 agonist GSK1842799 is described. Key features in the synthesis, which has been implemented on a multikilogram scale, include a nucleophilic aromatic substitution to install a lipophilic 1-octyloxy chain, introduction of a chiral quaternary centre, and the use of Lawesson’s reagent to form a thiadiazole ring. Due to the lack of crystalline intermediates, workup protocols that took advantage of the lipophilic nature of the compounds were developed. This allowed full combination of the five chemistry stages and a salt formation, with the only isolation being that of the final hemifumarate salt of the drug substance. The synthesis of the O -phosphorylated active metabolite is also described.",10.1021/op2000095,2011-03-10,0.6924336520456346
European Journal of Organic Chemistry,Synthesis of 5‐Fluorocytosine Using 2‐Cyano‐2‐fluoroethenolate as a Key Intermediate,"There is an urgent demand for 5‐fluorocytosine (5‐FC) due to its activity against HIV‐induced fungal infections as well as its use as a key intermediate in the synthesis of the clinically highly important anti‐HIV drug emtricitabine (FTC). We report a simple, low‐cost five steps synthesis of 5‐FC starting from chloroacetamide. Overall yields up to 46 % were achieved and the route is devoid of any chromatographic purifications. The previously unknown key intermediate ( Z )‐2‐cyano‐2‐fluoroethenolate is obtained through a Claisen‐type condensation from fluoroacetonitrile. As the direct cyclization with urea only gave poor yields, 5‐fluoro‐2‐methoxypyrimidin‐4‐amine, 5‐fluoro‐2‐(methylsulfanyl)pyrimidin‐4‐amine and 5‐fluoropyrimidine‐2,4‐diamine served as synthetic intermediates.",10.1002/ejoc.201900629,2019-06-05,0.6924194566311684
Organic Letters,Radical Approach to the Chiral Quaternary Center in Asperaculin A: Synthesis of 9-Deoxyasperaculin A,"Diastereoselective approaches toward the synthesis of a marine-derived sesquiterpenoid fungal metabolite, asperaculin A, are delineated, combining step economy and simplicity. Two distinct lactonization sequences from a common intermediate led to the first synthesis of 9-deoxyasperaculin A, a novel dioxa[5.5.5.6]fenestrane, in 14 steps (16% overall yield) and 16 steps (18% overall yield), respectively. [2,3]-Wittig-Still rearrangement and Ti(III)-mediated epoxide opening-cyclization were employed as some of the key steps for the stereoselective generation of the vicinal all-carbon quaternary centers of the target molecule.",10.1021/acs.orglett.6b03854,2017-01-20,0.6924155531720486
Organic Process Research & Development,Process Development and Manufacture of the Core Starting Material of Adagrasib (MRTX849),"β-Ketoester 1 is one of the critical starting materials used in the second-generation synthesis of adagrasib. Disclosed within is a new, streamlined, operationally simple, and more environmentally friendly three-step telescoped protocol which was demonstrated on a >100 kg batch with an overall yield of 70%. Identification of the shortcomings and the quality issues of the initial route are discussed. The process development work overcoming these challenges and leading to the new route of synthesis is described.",10.1021/acs.oprd.3c00485,2024-01-26,0.6924098089960837
Organic Process Research & Development,Development of a Practical and Convergent Process for the Preparation of Sulopenem,"Previous synthetic processes for the preparation of sulopenem involved multistep linear sequences in which the chiral sulfoxide side chain was introduced early in the process. This contribution summarizes the development of a practical and convergent process for the large-scale preparation of 1 . The key step in the synthesis involves cyclization of an oxalimide intermediate to provide the thiopenem core. This convergent strategy allows for late introduction of the expensive and labile chiral sulfoxide subunit. Additionally, a regioselective sulfur oxidation and an improved deprotection sequence were developed. The latter provides API of high purity without the need for recrystallization.",10.1021/op300131e,2012-07-13,0.6923755644767047
Tetrahedron,An efficient synthesis of the 4′-epimer of 2-fluoronoraristeromycin,,10.1016/j.tetlet.2012.01.047,2012-01-21,0.6923579502706488
Tetrahedron,"An efficient synthesis of daidzein, dimethyldaidzein, and isoformononetin",,10.1016/j.tetlet.2010.06.078,2010-06-20,0.6923579502706488
Tetrahedron,An Efficient Synthesis of Wiedendiol-A from (+)-Sclareolide,,10.1016/00404-0399(50)1023b-,1995-07-24,0.6923579502706488
Tetrahedron,Efficient synthesis of benzylphosphine oxides and E-stilbenes,,10.1016/s0040-4039(00)73481-2,1994-09-01,0.6923579502706488
Tetrahedron,Efficient synthesis of rottlerin and its two subunits,,10.1016/j.tetlet.2016.03.049,2016-03-15,0.6923579502706488
Tetrahedron,An efficient synthesis of the dolabellanes.,,10.1016/s0040-4039(00)61504-6,1993-12-01,0.6923579502706488
Tetrahedron,An efficient synthesis of futalosine,,10.1016/j.tetlet.2010.10.010,2010-10-11,0.6923579502706488
Tetrahedron,An efficient synthesis of cyercene A,,10.1016/j.tetlet.2004.06.125,2004-07-21,0.6923579502706488
Tetrahedron,An efficient synthesis of β-ketosilanes,,10.1016/s0040-4039(01)81141-2,1984-01-01,0.6923579502706488
Tetrahedron,Efficient synthesis of several aniba and magnolia neolignans,,10.1016/s0040-4039(01)99835-1,1983-01-01,0.6923579502706488
Tetrahedron,An efficient synthesis of N-cyclobutylmethylnoroxymorphone from thebaine,,10.1016/s0040-4039(01)93106-5,1977-01-01,0.6923579502706488
Tetrahedron,"An efficient synthesis of argemonine, a pavine alkaloid",,10.1016/s0040-4039(00)02233-4,2001-02-01,0.6923579502706488
Tetrahedron,"An efficient synthesis of thiazolo[3,2-a]pyrimidinones",,10.1016/j.tetlet.2010.04.052,2010-04-19,0.6923579502706488
Tetrahedron,An efficient synthesis of yuehchukene,,10.1016/s0040-4039(00)74483-2,1991-02-01,0.6923579502706488
Tetrahedron,"A very efficient synthesis of 1,8-diazaanthraquinones",,10.1016/s0040-4039(97)01006-x,1997-06-01,0.6923579502706488
Tetrahedron,An efficient entry into butenolides: Synthesis of (±) mintlactone,,10.1016/s0040-4039(00)61325-4,1992-08-01,0.6923579502706488
Tetrahedron,An efficient synthesis of 2-hydroxyphenylphosphonates,,10.1016/s0040-4039(01)81909-2,1981-01-01,0.6923579502706488
Tetrahedron,Efficient synthesis of 5′-O(N)-carbamyl and -polycarbamyl nucleosides,,10.1016/j.tetlet.2013.10.029,2013-10-11,0.6923579502706488
Tetrahedron,An efficient synthesis of Wiedendiol-A from (+)-sclareolide,,10.1016/0040-4039(95)01023-b,1995-07-01,0.6923579502706488
Tetrahedron,An efficient synthesis of (±)-pinidine,,10.1016/s0040-4039(00)89121-2,1985-01-01,0.6923579502706488
Tetrahedron,"An efficient synthesis of m-hydroxycocaine and m-hydroxybenzoylecgonine, two metabolites of cocaine",,10.1016/0040-4039(95)01178-k,1995-08-01,0.6923579502706488
Tetrahedron,An efficient synthesis of enyne[3]cumulenes,,10.1016/0040-4039(95)00606-d,1995-05-01,0.6923579502706488
Tetrahedron,"An Efficient Synthesis of m-Hydroxycocaine and m-Hydroxybenzoylecgonine, Two Metabolites of Cocaine",,10.1016/00404-0399(50)1178k-,1995-08-14,0.6923579502706488
Tetrahedron,An efficient synthesis of 4-chromanones,,10.1016/j.tetlet.2011.07.018,2011-07-24,0.6923579502706488
Tetrahedron,The efficient synthesis of amphiphilic oximes of galactose and glucosamine,,10.1016/j.tetlet.2012.02.086,2012-02-24,0.6923579502706488
Tetrahedron,Efficient synthesis of fluorescent rosamines: multifunctional platforms for cellular imaging,,10.1016/j.tetlet.2014.01.067,2014-01-24,0.6923579502706488
Tetrahedron,An efficient synthesis of (+)-prelactone B,,10.1016/j.tetlet.2004.06.121,2004-07-22,0.6923579502706488
Tetrahedron,An efficient synthesis of (−)-3-deazaaristeromycin,,10.1016/j.tetlet.2004.10.052,2004-11-01,0.6923579502706488
Tetrahedron,An efficient synthesis of (r)-carnitine,,10.1016/s0040-4039(00)91898-7,1992-02-01,0.6923579502706488
Tetrahedron,Efficient stereocontrolled synthesis of 2-benzimidazolyl- and 2-indolyl-C-nucleosides,,10.1016/s0040-4039(00)02029-3,2001-01-01,0.6923579502706488
Tetrahedron,An efficient synthesis of 9-phenanthrols,,10.1016/s0040-4039(00)85196-5,1986-01-01,0.6923579502706488
Tetrahedron,First synthesis of anomeric sulfimides - efficient glycosyl donors,,10.1016/s0040-4039(98)01837-1,1998-10-01,0.6923579502706488
Tetrahedron,"An efficient synthesis of the 1,6-dioxaspiro[4.4]nonan-2-one motif of the immunosuppressive triterpenoid Phainanoid F",,10.1016/j.tetlet.2017.09.091,2017-09-30,0.6923579502706488
Tetrahedron,An efficient synthesis of 5-azidotryptophan,,10.1016/s0040-4039(00)73405-8,1994-08-01,0.6923579502706488
Tetrahedron,An efficient synthesis of (+)-oxybiotin from d-arabinose,,10.1016/s0040-4039(02)00223-x,2002-03-01,0.6923579502706488
Tetrahedron,An efficient synthesis of varenicline,,10.1016/j.tetlet.2009.10.107,2009-10-28,0.6923579502706488
Tetrahedron,An efficient synthesis of leukotriene B4,,10.1016/s0040-4039(01)93886-9,1989-01-01,0.6923579502706488
Tetrahedron,An efficient synthesis of (+)-decursinol from umbelliferone,,10.1016/j.tetlet.2007.02.088,2007-02-23,0.6923579502706488
Tetrahedron,an efficient synthesis of N-cyclobutylmethyl- noxymorphone from thebaine,,10.1016/s0040-4039(01)83111-7,1977-01-01,0.6923579502706488
Tetrahedron,Efficient synthesis of (−)-(R)- and (+)-(S)-rolipram,,10.1016/j.tetlet.2017.09.080,2017-09-29,0.6923579502706488
Tetrahedron,Efficient synthesis of (+)-nojirimycin and (+)-1-deoxynojirimycin,,10.1016/0040-4039(90)80078-z,1990-01-01,0.6923579502706488
Tetrahedron,An efficient synthesis of α-Cuparenone,,10.1016/0040-4039(96)00345-0,1996-04-01,0.6923579502706488
Tetrahedron,"Efficient synthesis of deuterated 1,2,3-triazoles",,10.1016/j.tetlet.2010.09.097,2010-09-28,0.6923579502706488
Tetrahedron,Efficient synthesis of 2-trihalomethyl-5-cyanopyridines,,10.1016/s0040-4039(98)01731-6,1998-10-01,0.6923579502706488
Synthesis,An Efficient Synthesis of (<i>S</i>)-<i>O</i>-Benzylglycidol,,10.1055/s-1985-31248,1985-01-01,0.6923579502706488
Tetrahedron,Efficient synthesis of l-altrose and l-mannose,,10.1016/s0040-4039(00)00363-4,2000-04-01,0.6923579502706488
Tetrahedron,Efficient synthesis of triazoles from d-arabinose and l-fucose,,10.1016/s0040-4039(00)01356-3,2000-10-01,0.6923579502706488
Tetrahedron,Efficient stereocontrolled synthesis of the ABC subunit of dumsin,,10.1016/0040-4039(94)88451-x,1994-12-01,0.6923579502706488
Tetrahedron,An expeditious and efficient formal synthesis of (±)-aphidicolin,,10.1016/s0040-4039(00)78255-4,1994-08-01,0.6923579502706488
Tetrahedron,An efficient synthesis of nitriles from aldoximes,,10.1016/s0040-4039(00)77922-6,1976-02-01,0.6923579502706488
Tetrahedron,An efficient synthesis of pregaliellalactone and desoxygaliellalactone,,10.1016/j.tetlet.2014.04.117,2014-05-15,0.6923579502706488
Tetrahedron,Efficient synthesis of pyruvate ketals of carbohydrates,,10.1016/j.tetlet.2006.09.159,2006-10-19,0.6923579502706488
Tetrahedron,Efficient synthesis of carbohydrate thionolactones,,10.1016/j.tetlet.2006.03.104,2006-04-18,0.6923579502706488
Tetrahedron,Efficient synthesis of spiroisoxazoline oxindoles,,10.1016/j.tetlet.2011.10.139,2011-11-01,0.6923579502706488
Tetrahedron,An efficient synthesis of pyrido-imidazodiazepinediones,,10.1016/j.tetlet.2012.12.087,2013-01-04,0.6923579502706488
Tetrahedron,An efficient synthesis of (-)-bulgecinine,,10.1016/s0040-4039(00)74771-x,1992-12-01,0.6923579502706488
Tetrahedron,"Efficient synthesis of 2′,3′-dideoxynucleosides and 2′,3′-dideoxy C-nucleosides from D-glucosamine",,10.1016/s0040-4039(00)79561-x,1992-05-01,0.6923579502706488
Tetrahedron,"Efficient synthesis of the 6,6-spiroacetal of spirofungin A",,10.1016/s0040-4039(03)01184-5,2003-06-01,0.6923579502706488
Tetrahedron,An efficient synthesis of dihydrocoumarins,,10.1016/s0040-4039(00)91885-9,1992-02-01,0.6923579502706488
Tetrahedron,An efficient synthesis of indoloquinoline alkaloid—neocryptolepine (cryptotackieine),,10.1016/j.tetlet.2011.09.135,2011-10-14,0.6923579502706488
Tetrahedron,An efficient synthesis of sulfamides,,10.1016/j.tetlet.2010.03.106,2010-03-31,0.6923579502706488
Tetrahedron,An efficient synthesis of oosporein,,10.1016/j.tetlet.2009.06.103,2009-06-26,0.6923579502706488
Tetrahedron,An efficient synthesis of 1-H indazoles,,10.1016/j.tetlet.2007.07.162,2007-07-31,0.6923579502706488
Tetrahedron,"Efficient stereodivergent synthesis of 1,4-dideoxy-1,4-iminohexitols from an (S)-glyceraldimine",,10.1016/j.tetlet.2003.11.053,2003-12-09,0.6923579502706488
Tetrahedron,Efficient synthesis of deuterated olefins from arenesulfonylhydrazones,,10.1016/s0040-4039(00)75264-6,1975-01-01,0.6923579502706488
Tetrahedron,An efficient synthesis of the tamandarin B macrocycle,,10.1016/j.tetlet.2009.12.091,2009-12-24,0.6923579502706488
Tetrahedron,An efficient synthesis of semiplenamide C,,10.1016/j.tetlet.2005.06.027,2005-07-02,0.6923579502706488
Tetrahedron,Efficient synthesis of N-alkylformimidoyl cyanides,,10.1016/s0040-4039(99)01608-1,1999-10-01,0.6923579502706488
Tetrahedron,"An efficient synthesis of 5,5′-diaryl-2,2′-bichalcophenes",,10.1016/j.tetlet.2005.11.091,2005-12-06,0.6923579502706488
Tetrahedron,An efficient synthesis of N-monoalkylated hydroxylamines,,10.1016/s0040-4039(00)96265-8,1987-01-01,0.6923579502706488
Synthesis,"An Efficient Synthesis of 3,4,5-Trimethoxybenzaldehyde from Vanillin",,10.1055/s-1983-30315,1983-01-01,0.6923579502706488
Synlett,"Efficient Synthesis of (±)-Dihydrorhipocephalin,a Bioactive Terpenoid from Caribbean Marine Algae of the Genera<i>Penicillus</i>and<i>Udotea</i>",International audience,10.1055/s-2003-41008,2003-01-01,0.6923579502706488
Tetrahedron,The efficient synthesis of unsymmetrical oligo(phenylenevinylenes),,10.1016/j.tetlet.2007.11.073,2007-11-20,0.6923579502706488
Tetrahedron,Efficient synthesis of baicalin and its analogs,,10.1016/j.tetlet.2015.04.083,2015-04-26,0.6923579502706488
Organic Process Research & Development,An Improved Synthesis of Memantine Hydrochloride:  Anti-Alzheimer's Drug,"An economical new process route has been developed for the large-scale synthesis of memantine hydrochloride ( 1 ) an anti-Alzheimer's drug. The procedure involves the conversion of 1,3-dimethyl adamantane ( 2 ) to formamide intermediate 8 as a key step, followed by hydrolysis to (1-amino-3,5-dimethyl adamantane) hydrochloride ( 1) in good yield.",10.1021/op060246+,2007-02-15,0.6923470751053836
Organic Letters,"An Expeditious Synthesis of (±)-Desepoxy-4,5-didehydromethylenomycin A Methyl Ester","[formula: see text] A total synthesis of the racemic methyl ester of desepoxy-4,5-didehydromethylenomycin A has been achieved in six steps with an overall yield of 31% starting from diethyl methanephosphonate. The key steps include the Nazarov cyclization of the dienone 7 leading to the alpha-phosphoryl cyclopentenone 8 and the Horner-Wittig reaction of the latter employed for the introduction of the exocyclic methylene moiety.",10.1021/ol005742b,2000-03-23,0.692338599752775
Journal of Organic Chemistry,"Short Synthesis of Enantiopure <i>C</i><sub>2</sub>-Symmetric 1,2:4,5-Diepoxypentane and “<i>Pseudo</i>”-<i>C</i><sub>2</sub>-Symmetric 3-Azido-1,2:4,5-diepoxypentane from Arabitol","On the basis of our previously described selective protection of arabitol as its 1,2:4,5-bis-pentylidene acetal 5, we report a straightforward synthesis of the novel ""pseudo""-C(2)-symmetric 3-azido-1,2:4,5-diepoxypentane building block 4 in 6 steps from arabitol. Using a similar synthetic route, an improved synthesis of the C(2)-symmetrical 1,2:4,5-bis-epoxypentane building block 1 is described, also in 6 steps from arabitol. Both enantiomers of 1 and 4 are accessible, and all reactions involved are easily amenable for large-scale synthesis.",10.1021/jo034374x,2003-09-23,0.6922953403228094
Tetrahedron,A novel one-step synthesis of pyrimidines and condensed pyrimidines,,10.1016/s0040-4039(01)97851-7,1970-01-01,0.6922489266586243
Synthesis,"A Novel, Two-Step Synthesis of 2-Methoxyestradiol",,10.1055/s-1977-24304,1977-01-01,0.6922489266586243
Journal of Organic Chemistry,Synthesis of Maradolipid,"The first synthesis of maradolipid, a unique dissymmetrically 6,6'-di-O-acylated trehalose glycolipid isolated from C. elegans, is accomplished in five steps starting from trehalose in 45% overall yield. The short synthesis relies on dissymmetrization of trehalose core via regioselective acylation of a 2,3,4,2',3',4'-hexa-O-TMS trehalose 6,6'-diol derivative as a key step.",10.1021/jo200979n,2011-07-08,0.6922049696875502
Organic Process Research & Development,"Development of a Gram-Scale Synthesis of PBRM, an Irreversible Inhibitor of 17β-Hydroxysteroid Dehydrogenase Type 1","Efforts toward the development of a reliable gram-scale synthesis of 3-{[(16β,17β)-3-(2-bromoethyl)-17-hydroxyestra-1,3,5(10)-trien-16-yl]methyl}benzamide (PBRM), a potent and selective steroidal covalent inhibitor of 17β-hydroxysteroid dehydrogenase type 1, are described. Among the three synthetic routes (C–E) developed herein, route E is the most efficient one with only six chemical steps from commercially available estrone, and an overall yield of 13% leading to PBRM with a high-HPLC-grade purity (99.7%) after recrystallization. Important improvements have been achieved in this sequence from previously reported routes (A and B). Notably, we used a palladium-catalyzed Suzuki–Miyaura cross-coupling reaction to rapidly install the requested C3 chain on estrone. Also, catalytic hydrogenation of the C16-enone was shortened by half using Pearlman’s catalyst. Finally, we used a selective bromination through deoxygenation of alcohol at the last step of the sequence to provide PBRM without dehydration of its carboxamide functionality, a persistent problem observed in other routes. Crystals of PBRM were also obtained from recrystallization in acetonitrile and submitted to X-ray analysis, which confirmed the PBRM structure. This work now makes it possible to start a proof-of-principle in a nonhuman primate model for the treatment of endometriosis, while supporting its future pharmacological development.",10.1021/acs.oprd.8b00402,2019-09-19,0.6921743313393298
Organic Process Research & Development,Successful Development and Scale-up of a Palladium-Catalysed Amination Process in the Manufacture of ZM549865,"Key steps in the synthesis of ZM549865 (a 5-HT receptor antagonist) are the palladium-catalysed amination of ethyl 8-bromo-6-fluoro-4-oxo-4 H -2-chromenecarboxylate and subsequent hydrolysis of the ester group. The development of a simple, robust process capable of making multikilogram amounts of the required intermediate is described. Performing the amination step at 125 °C instead of 80 °C and optimising the hydrolysis conditions led to an increase in overall yield from 44% to about 70% as well as reducing the reaction time from days to hours. The chromone ring was initially constructed by reaction of 2-bromo-4-fluorophenol with dimethyl acetylenedicarboxylate followed by cyclisation. A potentially cheaper route was developed that involved formation of a substituted acetophenone via the Fries rearrangement, followed by condensation with diethyl oxalate and cyclisation.",10.1021/op0499369,2004-09-16,0.6920798582623021
Organic Letters,"Asymmetric Synthesis of MK-7845, an Investigational Treatment for COVID-19","An enantioselective seven-step synthesis of MK-7845, an investigational protease inhibitor for the treatment of COVID-19 is described. Key features of the synthesis include the preparation of a chiral isonitrile intermediate utilizing an asymmetric ruthenium-catalyzed reductive amination reaction to set the key amine stereocenter; a highly enantioselective, biocatalytic oxidation reaction with a monoamine oxidase enzyme to furnish a bicyclic imine; and, finally, the union of these fragments via a diastereoselective three-component Joullié-Ugi coupling reaction en route to MK-7845.",10.1021/acs.orglett.5c03920,2025-10-30,0.6920593568128328
Journal of Organic Chemistry,A Practical and Efficient Synthesis of the Selective Neuronal Acetylcholine-Gated Ion Channel Agonist (<i>S</i>)-(−)-5-Ethynyl-3-(1-methyl-2-pyrrolidinyl)pyridine Maleate (SIB-1508Y),"An efficient, high-yielding synthetic procedure for the preparation of the novel neuronal acetylcholine-gated ion channel agonist ( S )-(−)-5-ethynyl-3-(1-methyl-2-pyrrolidinyl)pyridine maleate [( S )- 2, SIB-1508Y] is described. The key steps in the process include the lithium bis(trimethylsilyl)amide-mediated acylation of N -vinylpyrrolidinone with ethyl 5-bromonicotinate, a high-yielding sodium borohydride reduction of imine 5, and a new heteroaryl−alkyne cross-coupling protocol for the introduction of the ethyne moiety in ( S )- 2 . The preparation of enantiomerically pure ( S )- 2 was accomplished via a combination of enantioselective reduction of imine 5 and crystallization of enantiomerically enriched 5-bromo-3-(1-methyl-2-pyrrolidinyl)pyridine ( 7 ) as the dibenzoyl- l -tartaric acid salt.",10.1021/jo971572d,1998-01-30,0.6919976014102444
Journal of Organic Chemistry,Practical Route to a New Class of LTD<sub>4</sub> Receptor Antagonists,"A general approach to the synthesis of a new class of LTD 4 antagonists is presented. The key diarylpropane framework was prepared by Claisen−Schmidt condensation and selective reduction of the enone. Depending on the bridge to the 7-chloroquinaldine moiety, alkylation or Heck coupling methodology was developed. The chiral sulfides were introduced by asymmetric reduction of the diarylpropanone intermediates and subsequent inversion of the chiral center.",10.1021/jo952103j,1996-01-01,0.69195842985784
Angewandte Chemie International Edition,Total Synthesis of (±)‐Alstoscholarisine A,"The first total synthesis of the neuroactive indole alkaloid (±)-alstoscholarisine A is reported. The key step of the concise synthesis is an efficient domino sequence that was used to assemble the 2,8-diazabicyclo[3.3.1]nonane core through the formation of two C-N bonds and one C-C bond in a single step.",10.1002/anie.201510777,2016-01-12,0.6919444836295698
Synthesis,A New High-Yield One-Step Synthesis of Phenylpropynenitrile,,10.1055/s-1976-24073,1976-01-01,0.6919430721609471
Tetrahedron,Development of a convenient synthetic route to aminochromenes via Buchwald C–N coupling,,10.1016/j.tetlet.2007.04.003,2007-04-07,0.6918986240165311
Journal of Organic Chemistry,An Expedient Route to a Potent Gastrin/CCK-B Receptor Antagonist (+)-AG-041R,"An enantiocontrolled synthesis of (+)-AG-041R (1), a potent gastrin/CCK-B receptor antagonist, has been achieved employing a chiral rhodium(II)-catalyzed, oxidative intramolecular aza-spiroannulation as the key step.",10.1021/jo901352u,2009-08-31,0.6918460198953359
Organic Process Research & Development,Development an Efficient Route to the 5-Lipoxygenase Inhibitor PF-04191834,"A convergent six-step process for the synthesis of PF-04191834 ( 1 ), a potent and selective 5-lipoxygenase inhibitor, has been developed and used to deliver over 20 kg of API. The process uses the same bond-forming steps as the initial medicinal chemistry route, including the use of two consecutive Pd-catalyzed Ar–S couplings to form the key diaryl thioether linkage. The reaction conditions and downstream processing have been optimized to eliminate column chromatography and aqueous work-ups and to minimize disproportionation of 1, to ensure successful scale-up.",10.1021/op200173g,2011-08-18,0.6918353482788082
Organic Letters,"Synthesis of Slagenins A, B, and C","[structure: see text] A short synthesis of the marine sponge metabolites slagenins A (1), B (2), and C (3) is described. The synthetic route features the preparation of beta-hydroxyimidazolone 4 from ornithine and its subsequent oxidative cyclization to the slagenin core.",10.1021/ol000233v,2000-09-29,0.6918035756095036
Journal of the American Chemical Society,"A Concise, Efficient and Scalable Total Synthesis of Thapsigargin and Nortrilobolide from (<i>R</i>)-(−)-Carvone","A concise, efficient and scalable synthesis of thapsigargin and nortrilobolide from commercially available (R)-(-)-carvone was developed. Our synthetic strategy is inspired by nature's carbon-carbon bond formation sequence, which facilitates the construction of a highly functionalized sesquiterpene lactone skeleton in five steps via an enantioselective ketone alkylation and a diastereoselective pinacol cyclization. We envision that this strategy will permit the construction of other members of the family, structural analogs and provide a practical synthetic route to these important bioactive agents. In addition, we anticipate that the prodrug Mipsagargin, which is currently in late-stage clinical trials for the treatment of cancer, will also be accessible via this strategy. Hence, the limited availability from natural sources, coupled with an estimated demand of one metric ton per annum for the prodrug, provides a compelling mandate to develop practical total syntheses of these agents.",10.1021/jacs.7b01734,2017-04-19,0.6917636069615307
Journal of Organic Chemistry,Total Synthesis of the Marine Pyridoacridine Alkaloid Demethyldeoxyamphimedine,"A four-step total synthesis of the marine pyridoacridine alkaloid demethyldeoxyamphimedine (5) is presented. With an overall yield of 6.4%, this pentacyclic compound has been synthesized by utilizing only two commercial building blocks, ethyl nicotinate and 2-iodoaniline. The final cyclization step was achieved via a directed remote ring metalation with Knochel-Hauser base (TMPMgCl·LiCl) followed by intramolecular trapping of an ester group.",10.1021/jo501312d,2014-07-15,0.6917215662610482
Synthesis,SYNTHESIS–SYNLETT Lecture: Toward the Asymmetric Synthesis of Tetrapetalone A: Preparation of an Enantioenriched Indane Intermediate and Strategy for Endgame Glycosylation,"A chiral auxiliary is employed to obtain, via Nazarov cyclization, a synthetic intermediate crucial to our previously reported synthesis of the tetrapetalone A core. This indane derivative, corresponding to the A and B rings of the tetrapetalone natural product skeleton, is then used to test an endgame strategy for installation of the β-rhodinosyl group on ring B. A palladium-catalyzed decarboxylative coupling is described that effects the exclusive formation of the desired β-glycosidic linkage, and the target rhodinose moiety can be obtained via hydrogenation.",10.1055/s-0036-1591747,2018-01-05,0.6917102360234364
Journal of the American Chemical Society,A Second-Generation Synthesis of the C1−C28 Portion of the Altohyrtins (Spongistatins),"A practical second-generation synthesis of an advanced intermediate in our total synthesis of altohyrtin C (spongistatin 2) has been developed. A new approach to the C1-C15 (AB) portion features a vinyllithium addition to an aldehyde followed by a palladium-catalyzed allylic reduction to install the troublesome C13-C15 segment. Our general approach to the C16-C28 (CD) spiroketal has been retained, but some improvements have been made. Most notably, the kinetically controlled CD-spiroketalization reaction now proceeds in high yield with excellent diastereoselection. This new strategy uses the anti-aldol coupling used in our first-generation synthesis to join AB and CD fragments. A total of 9.6 g of intermediate 57 has been produced using this improved route.",10.1021/ja030316h,2003-09-27,0.6916686664235281
Journal of Organic Chemistry,A New Ring Expansion for a Chiral Hexahydroazulene Skeleton Possessing an Angular Methyl Group,"A new synthetic route for a pseudoguaiane ring system is described. The synthesis features an Ireland-Claisen rearrangement for constructing the trans-fused ring system, followed by a new ring expansion to yield a bicyclo[5.3.0]decane ring system possessing an angular methyl group.",10.1021/jo201153h,2011-07-01,0.691656883044655
Journal of Organic Chemistry,Protecting-Group-Free Formal Synthesis of Aspidospermidine: Ring-Opening Cyclization of Spirocyclopropane with Amine Followed by Regioselective Alkylations,"A concise formal synthesis of (±)-aspidospermidine via Stork’s intermediate, which could be used as a divergent synthesis of Aspidosperma alkaloids, was achieved by employing a ring-opening cyclization of spirocyclopropane with amine followed by a regioselective intramolecular/intermolecular alkylation sequence. Stork’s intermediate was synthesized in only six steps from a simple starting material, 1,3-cyclohexanedione, and was converted into (±)-aspidospermidine. To the best of our knowledge, this synthesis of Stork’s intermediate involves the least number of steps to date. Furthermore, no protecting groups were used during this synthesis.",10.1021/acs.joc.9b02469,2019-11-20,0.6916247567843407
Synthesis,Synthesis of the C1–C12 Fragment of Calyculin C,"Calyculins are a class of highly cytotoxic metabolites originally isolated from the marine sponge Discodermia calyx. To date, a total of twelve different calyculins (A–J) and calyculinamides (A, B and F) have been described, the most abundant (in D. calyx) being calyculins A and C. Herein, we demonstrate a concise route to access the C1–C12 tetraene fragment of calyculin C using transition-metal-catalyzed coupling reactions (Suzuki–Miyaura, Stille, Negishi and Heck) for the key connections. The synthesis starts from propionaldehyde and proceeds in 10 steps with 7.5% overall yield. We also describe an efficient route for the preparation of (Z)-3-iodobut-2-enenitrile in four steps and 68% yield.",10.1055/s-0037-1610387,2018-11-22,0.6916168072646037
Tetrahedron,Stereocontrolled synthesis of key intermediates in the total synthesis of acetogenins of annonaceae,,10.1016/s0040-4039(00)61460-0,1993-12-01,0.6915978959787177
Journal of Organic Chemistry,A Total Synthesis of (−)-Hemiasterlin Using <i>N</i>-Bts Methodology,"A total synthesis of (-)-hemiasterlin has been accomplished in nine steps from 25(8) (>35% yield overall). An improved enantiocontrolled route to the tetramethyltryptophan subunit 32 was developed using an asymmetric Strecker synthesis (five steps, 50% yield from 25), and the dipeptide 22 was prepared in seven steps, 37% yield from valinol. The synthesis exploits the high reactivity of a Bts-protected amino acid chloride in the difficult peptide coupling of sterically hindered amino acid residues 18 and 20 to form 21 (70%, recrystallized) and also uses N-Bts intermediates for the high-yielding N-methylations of 14 and 31. In addition, the Bts-protected di-tert-butyl N-acylimidodicarbonate 33 is shown to undergo efficient coupling with 22 to form 34 (97% in the coupling step; 79% over the activation; coupling sequence from 32).",10.1021/jo0104882,2001-09-28,0.6915289937000134
Angewandte Chemie International Edition,"Asymmetric, Stereocontrolled Total Synthesis of Paraherquamide A","Paraherquamide A (1), a potent anthelmintic agent, isolated from various Penicillium species with activity against ivermectin-resistant intestinal parasites, has been synthesized. The synthesis of a key intermediate, the α-isoprenylated, β-substituted hydroxyproline derivative, exploited a highly diastereoselective intramolecular SN2′ cyclization as a key step. This procedure is the first asymmetric, stereocontrolled, total synthesis of 1.",10.1002/1521-3773(20000717)39:14<2540::aid-anie2540>3.0.co;2-r,2000-07-17,0.6914949562351947
Journal of Organic Chemistry,"Synthesis of 1-(<i>tert</i>-Butyl) 4-Methyl (1<i>R</i>,2<i>S</i>,4<i>R</i>)-2-Methylcyclohexane-1,4-dicarboxylate from Hagemann’s <i>tert</i>-Butyl Ester for an Improved Synthesis of BMS-986251","We describe an efficient synthetic route to differentially protected diester, 1-( tert -butyl) 4-methyl (1 R,2 S,4 R )-2-methylcyclohexane-1,4-dicarboxylate (+)- 1, via palladium-catalyzed methoxycarbonylation of an enol triflate derived from a Hagemann’s ester derivative followed by a stereoselective Crabtree hydrogenation. Diester 1 is a novel chiral synthon useful in drug discovery and was instrumental in the generation of useful SAR during a RORγt inverse agonist program. In addition, we describe a second-generation synthesis of the clinical candidate BMS-986251, using diester 1 as a critical component.",10.1021/acs.joc.0c01169,2020-07-20,0.6914754849702964
Tetrahedron,A novel route to a new lactone intermediate for C-nucleosides via an intramolecular sulfonium ylide rearrangement. A formal synthesis of (+)-showdomycin,,10.1016/s0040-4039(00)60417-3,1993-11-01,0.6914648266655395
Synthesis,Improved Synthesis of MDL 73811 – A Potent AdoMetDC Inhibitor and Anti-Trypanosomal Compound,"An improved synthesis of MDL 73811 – a potent AdoMetDC ( S -adenosylmethionine decarboxylase) inhibitor and anti-trypanosomal compound with in vivo activity – has been completed in four steps from commercially available 2′,3′- O -isopropylideneadenosine. Utilization of Mitsunobu chemistry was crucial for the reliable and scalable introduction of the 5′-methylamine moiety, which was problematic using traditional activation/displacement chemistry as previously reported. All reactions in this synthesis were run on gram-scale resulting in a five-fold increase in yield over the original synthesis.",10.1055/s-0035-1561608,2016-04-13,0.6914533532409582
Organic Letters,"Catalytic, Enantioselective Formal Synthesis of Monoterpene Indole Alkaloid (−)-Alstoscholarine","A catalytic, enantioselective formal synthesis of monoterpene indole alkaloid (−)-alstoscholarine is described. The synthesis employs an Ir-amine dual catalyzed asymmetric allylation of aldehyde 8 with 3-indolyl vinyl carbinol derivative 7 to furnish chiral aldehyde 6 as a key asymmetric step. Other key reactions include the construction of the 2-ketopyrrole moiety by Nicolaou’s method and Tf 2 O promoted Pictet–Spengler cyclization to access Zhu’s intermediate 3 .",10.1021/acs.orglett.9b03319,2019-10-09,0.6913487110663153
Angewandte Chemie International Edition,Total Synthesis of Spirastrellolide A Methyl Ester—Part 1: Synthesis of an Advanced C17–C40 Bis‐spiroacetal Subunit,Out of the blue: The marine macrolide spirastrellolide A is a potent and selective inhibitor of protein phosphatase 2A and a lead for anticancer therapies. A flexible and modular synthetic strategy has been developed with two routes for the construction of the DEF bis-spiroacetal subunit. The optimized Suzuki coupling approach results in the efficient preparation of a C17–C40 aldehyde that forms the cornerstone of the first total synthesis.,10.1002/anie.200705565,2008-02-28,0.6912988839096118
Synlett,Concise Total Synthesis of Vicenistatin,A highly convergent total synthesis of macrocyclic lactam glycoside vicenistatin is described. Key features of the synthesis include rapid assembly of the macrolactam part and macrocyclic ring closure via intramolecular Stille coupling.,10.1055/s-0030-1258574,2010-09-23,0.6912539815607204
Journal of Organic Chemistry,Total Synthesis of (−)-Bitungolide F,"An efficient total synthesis of (-)-bitungolide F (6) in 17 steps and 20.1% yield is described herein. Key steps involve a Myers asymmetric alkylation to introduce the C6 methyl with proper stereochemistry, a Claisen-like cyclization to construct the alpha,beta-unsaturated delta-lactone and a Julia-Kocienski olefination to assemble the conjugated diene moiety.",10.1021/jo9000146,2009-03-09,0.6912515296333906
Organic Letters,Total Synthesis of a Trehalose-Containing Lipooligosaccharide Analogue from <i>Mycobacterium linda</i>,A short and efficient methodology has been developed to synthesize an analogue of a lipooligosaccharide from Mycobacterium linda isolated from Crohn’s disease. The total synthesis of the tetrasaccharide was achieved via a convergent [2 + 2] glycosylation approach. The key features of the synthesis involve the selective functionalization of a trehalose core via highly regioselective acylations and regioselective glycosylations. The synthesis was completed via a longest linear sequence of 14 steps in a 14.2% overall yield.,10.1021/acs.orglett.3c00378,2023-03-03,0.6912460084460814
European Journal of Organic Chemistry,A Stereoselective Catalytic Nitroaldol Reaction as the Key Step in a Strategy for the Synthesis of the Renin Inhibitor Aliskiren,"Abstract Aliskiren is the first‐in‐class orally active direct renin inhibitor. It was approved in 2007 for the treatment of hypertension. We have designed a new strategy for the convergent synthesis of aliskiren that involves a catalytic stereoselective nitroaldol reaction as the key step. A new enantiopure nitroalkane (synthon A 1 ), prepared in only three steps from a commercially available enantiopure 2‐(arylmethyl)‐3‐methyl butanol derivative, was successfully used in a copper‐catalysed Henry reaction to give a nitrolactone intermediate in which the correct configuration for the final product was established at all four stereocentres. Nitro‐group reduction, Boc‐protection of the resulting amine, aminolysis of the lactone with 3‐amino‐2,2‐dimethylpropionamide, and finally Boc‐deprotection led to the enantiopure renin inhibitor aliskiren.",10.1002/ejoc.201403659,2015-03-02,0.691192376278318
Synthesis,Suberosanes as Potential Antitumor Agents: First Enantioselective Total Synthesis of (1S)-Suberosanone and Configurational Assignment of Suberosenol A,"The first enantioselective total syntheses of two marine sesquiterpenes, natural (1 S )-suberosanone and (1 S )-suberosenol A, are achieved leading to the assignment of the absolute configuration of natural suberosenol A. A new access to (1 S )-suberosenone from a key tricyclic enone was also developed leading to an overall improvement of the synthesis, allowing an efficient route to suberosenol A. Hyperbaric asymmetric Michael addition and a highly efficient silver trifluoroacetate mediated α-alkylation for the formation of ring A completed the key steps of the synthesis. Regrettably, synthetic (1 S )-suberosanone did not retain the reported picomolar cytotoxic activity displayed by the natural product, the reason for which remains to be elucidated.",10.1055/s-0035-1561430,2016-04-20,0.6911907102446404
Organic Process Research & Development,Practical Synthesis of A Macrocyclic HCV Protease Inhibitor: A High-Yielding Macrolactam Formation,"A practical synthesis of a macrocyclic HCV protease inhibitor, MK-1220, is described. The key features are a new synthesis of the trisubstituted isoquinoline, Sonogashira fragment coupling, and a high-yielding, 18-membered macrolactam formation.",10.1021/op400331j,2014-02-25,0.6911755495369447
Organic Letters,Enantioselective Total Synthesis of (+)-Cassiol,An enantioselective total synthesis of (+)-cassiol is reported. The complex derived from Pd(2)(pmdba)(3) and enantiopure t-BuPHOX ligand catalyzes enantioconvergent decarboxylative alkylation to generate the quaternary carbon stereocenter at an early stage. The overall synthetic strategy involves a convergent late-stage coupling of two fragments. The synthesis features a longest linear sequence of eight steps.,10.1021/ol802410t,2008-12-18,0.6911173507991705
Organic Process Research & Development,Development of a Scalable Strategy for the Synthesis of PI3Kδ Inhibitors: Selective and Efficient Functionalization of Purine Derivatives,"The first-generation development route used to prepare the PI3Kδ inhibitor GNE-293 ( 3 ) for early toxicology studies is described. Through the use of a metal-free S N Ar reaction in place of a Pd-catalyzed C–N coupling, the synthesis was both simplified and made more reproducible in preparation for scale-up by reducing the number of operations required for purification and eliminating the need for column chromatography. The utility of the recently developed reagent TMPZnCl·LiCl is highlighted by a novel method of iodination to access the key aryl halide intermediate.",10.1021/op300235t,2012-12-19,0.6910797887615573
Journal of Organic Chemistry,A Convergent Total Synthesis of the Michellamines,"A convergent total synthesis of the anti-HIV michellamines ( 1 ) is described. The tetraaryl skeleton of the michellamines was constructed by formation first of the inner (nonstereogenic) biaryl axis and subsequently of the two other (stereogenic) axes in a highly convergent manner. The key transformation features a double Suzuki-type cross-coupling reaction between binaphthalene ditriflate 26 and isoquinolineboronic acid 35 . Ditriflate 26 is synthesized in six steps starting from diene 6 and 2,6-dibromobenzoquinone ( 9 ) in 21% overall yield. For large scale production of 26, a substantially shortened version of an existing procedure for the preparation of bisnaphthoquinone 13 was also developed, which allows for the preparation of 13 from benzoquinone and diene 6 in five steps and 67% overall yield. Binaphthoquinone 13 was subsequently converted into ditriflate 26 in three steps and 67% overall yield. By the described synthetic strategy, michellamines A ( 1a ) and B ( 1b ) are produced ( 1a: 1b = 1:2.5) in 24.6% overall yield from diene 6 . Curiously, none of the nonnaturally occurring atropoisomer 1c is formed.",10.1021/jo971495m,1998-01-27,0.6910620585130216
Organic Process Research & Development,Development of a Concise Scaleable Synthesis of 2-Chloro-5-(pyridin-2-yl) Pyrimidine via a Negishi Cross-Coupling,"A practical and scaleable synthesis of 2-chloro-5-(pyridin-2-yl) pyrimidine, an intermediate in the synthesis of a selective PDE-V inhibitor, was developed. A Negishi cross-coupling between the in situ prepared 2-pyridylzinc chloride and 5-iodo-2-chloropyrimidine catalyzed by Pd(PPh 3 ) 4 afforded the product in one step. Development of a convenient purification did away with the necessity of chromatography, allowing the preparation of the product on kilogram scale.",10.1021/op060241c,2007-02-17,0.6910369677644016
Organic Process Research & Development,A Chemoenzymatic Route to Chiral Intermediates Used in the Multikilogram Synthesis of a Gamma Secretase Inhibitor,"A chemoenzymatic route for the production of an intermediate to a gamma secretase inhibitor is described. The route is robust and was run at multikilogram scale. The process employs both a transaminase catalyzed reductive amination of a substituted tetralone and an alcohol dehydrogenase catalyzed reduction of an α-ketoester to generate the two chiral centers in the molecule, with nearly perfect stereoselectivity. The process also features simple isolation schemes, including a direct drop isolation of the aminotetralin phosphate salt.",10.1021/acs.oprd.7b00096,2017-05-22,0.691029187221426
Tetrahedron,"Total synthesis of (−)-Allosamidin, an insect chitinase inhibitor, employing chitin as a key starting material",,10.1016/s0040-4039(00)60825-0,1992-01-01,0.6910210019009281
Organic Letters,Stereocontrolled Synthesis of a Sphingomyelin Methylene Analogue as a Sphingomyelinase Inhibitor,"[reaction: see text]Efficient synthesis of a sphingomyelin methylene analogue, which was designed as a sphingomyelinase inhibitor, was stereoselectively achieved. The Hofmann rearrangement of the alpha-hydroxyethyl-beta-hydroxy amide 4 followed by the intramolecular oxazolidinone ring formation was one of the key steps.",10.1021/ol006147c,2000-08-01,0.690983006939829
Organic Letters,"Simple and Efficient Synthesis of (+)-Methyl 7-Benzoylpederate, a Key Intermediate toward the Mycalamides","A simple and efficient method for the synthesis of (+)-methyl 7-benzoylpederate, the left half of pederin, mycalamides, onnamides, and theopederins, was developed. The key reactions include the Evans asymmetric aldol reaction, a thioacetalization−lactonization, a stereoselective Claisen condensation, and a Takai−Nozaki olefination. The synthesis requires only nine steps and proceeds in 26% overall yield.",10.1021/ol990936g,1999-09-01,0.6909240880693601
Journal of Organic Chemistry,Stereoselective Synthesis of Cytotoxic Anhydrophytosphingosine Pachastrissamine [Jaspine B],"A practical stereoselective synthesis of cytotoxic anhydrophytosphingosine pachastrissamine (jaspine B) was achieved in 48% overall yield from D-(-)-tartaric acid. Key features of the sequence include the diastereoselective formation of a tetrol with three contiguous chiral centers, which was further elaborated to pachastrissamine. The synthetic route is operationally simple, diastereoselective and is amenable for the synthesis of a number of analogues of pachastrissamine.",10.1021/jo0707838,2007-07-11,0.6908892402014545
Synthesis,Stereoselective Total Synthesis of (+)-Brevipolide H from d-Galactal,"Abstract An efficient and concise synthesis of cytotoxic 5,6-dihydro-α-pyrone (+)-brevipolide H has been accomplished in 12 long linear steps in 8.65% overall yield from readily available chiral synthons, d-galactal and ethyl l-lactate. The features of this synthesis are highly diastereoselective Simmons–Smith cyclopropanation and carbohydrate-based chiron approach to rapid access to key 5,6-dihydro-α-pyrone skeleton.",10.1055/a-1700-3520,2021-11-17,0.6908834507097422
Organic Process Research & Development,Practical Asymmetric Synthesis of a Chiral Piperazinone Derivative,"A practical asymmetric route to a chiral piperazinone derivative, a fragment of MK-3207, is reported. The amine-bearing benzylic stereocenter is introduced via an asymmetric Pd-catalyzed hydrogenation of a cyclic sulfimidate in the presence of a chiral phosphine ligand. An efficient synthesis of the hydrogenation substrate is described, together with process development of the hydrogenation step and elaboration of the resulting cyclic sulfamate product to the desired piperazinone.",10.1021/op400150w,2013-07-12,0.6908531369649313
Organic Process Research & Development,Efficient and Scalable Synthesis of Ketoprofen: A Pyrolytic Aromatization Approach,"The practical synthesis of the representative nonsteroidal anti-inflammatory drug ketoprofen has been accomplished in 44% overall yield on the decagram scale. The key features in this synthetic work involve a TiCl 4 –Et 3 N mediated aldol/enol-lactonization annulation to affect dihydrobenzofuranone core formation and the use of a highly efficient pyrolytic aromatization condition to facilitate the construction of the vital 2-arylpropionic acid (2-APA) moiety. Furthermore, the avoidance of hazardous chemicals and crystallization of several intermediates would be greatly beneficial to the scalable synthesis of ketoprofen.",10.1021/acs.oprd.3c00049,2023-05-04,0.6908249574338906
Tetrahedron,"Synthetic studies on (+)-aplasmomycin. 2. Stereoselective synthesis of Corey's key intermediate, a formal total synthesis",,10.1016/s0040-4039(00)87805-3,1986-01-01,0.6908201811518971
Tetrahedron,"An efficient route to a 5,6-dihydropyrano[3,4-b]pyridin-8-one core in two steps from enaminolactones",,10.1016/j.tetlet.2007.12.106,2007-12-26,0.6908168919336849
Journal of Organic Chemistry,Efficient Total Synthesis of (−)-<i>cis</i>-Clavicipitic Acid,An efficient total synthesis of (-)-cis-clavicipitic acid has been achieved in seven linear steps (42% overall yield) from the known compound 6. The present synthesis features a palladium-catalyzed indole synthesis to provide the optically pure 4-chlorotryptophan derivative and a Heck reaction using aryl chloride as partner. It has also been discovered that the key azepinoindole nucleus could be stereoselectively constructed via a Mg(ClO(4))(2)-mediated intramolecular aminocyclization.,10.1021/jo9012755,2009-07-29,0.6908062110822575
Organic Process Research & Development,Synthesis of Injectable Antifungal Sch 59884,A synthesis for the preparation of multikilogram quantities of the injectable antifungal Sch 59884 is described.,10.1021/op010212w,2001-10-12,0.6907841078060556
Tetrahedron,"A novel synthesis of the (2R,3S)- and (2S3R)-3-amino-2-hydroxycarboxylic acid derivatives, the key components of a renin inhibitor and bestatin, from methyl (R)- and (S-mandelate",,10.1016/s0040-4039(00)89018-8,1990-01-01,0.6907469131177061
Organic Process Research & Development,Enantioselective Synthesis of a Key Intermediate in a New Process for Orlistat Using Asymmetric Hydrogenation and a Grignard Reagent Promoted Lactone Cyclization,"A new enantioselective synthesis of Orlistat suitable for large-scale preparation is described. Therein, the first isolated key intermediate ( R )-3-hexyl-5,6-dihydro-4-hydroxy-6-undecyl-2 H -pyran-2-one ( 12 ) is prepared via (a) the asymmetric hydrogenation of methyl 3-oxotetradecanoate to ( S )-3-hydroxytetradecanoate ( 9 ); (b) the acylation of 9 with 2-bromooctanoyl halide (bromide/chloride) to ( R )-3-[(2-bromo-1-oxooctyl)oxy]-tetradecanoic acid methyl ester ( 11 ) and finally (c) the tert -butyl magnesium chloride promoted cyclization of 11 to the single enantiomer 12 . The single enantiomer intermediate 12, previously published as a mixture of enantiomers 2, has been carried on through several steps to Orlistat ( 1 ) without any process changes.",10.1021/op060208q,2007-01-09,0.690705897489669
Organic Process Research & Development,Optimization of the Manufacturing Route to PF-610355 (1): Synthesis of Intermediate <b>5</b>,"Tertiary carbinamine 5 is an isolated intermediate in the synthesis of a novel, inhaled β-2 adrenoreceptor agonist PF-610355 . Process development for the key amide-formation and Ritter reactions, together with reaction understanding studies are discussed in context of the synthesis of 5 . The optimized process employed to manufacture 140 kg of 5 is described, and was shown to have superior metrics to the preliminary commercial route.",10.1021/op300341n,2013-02-05,0.6906975968599341
Organic Letters,Efficient Total Synthesis of (−)-Kaitocephalin,"A highly diastereoselective total synthesis of (-)-kaitocephalin, a novel antagonist of ionotropic glutamate receptors, was accomplished in 12 steps starting from 5-substituted proline ester via the aldol reaction with OBO-serine aldehyde, (E)-selective alpha,beta-dehydroamino acid synthesis using a new HWE reagent, and catalytic hydrogenation.",10.1021/ol9019343,2009-09-18,0.6906696434030353
Organic Letters,Studies toward the Synthesis of Potent Anti-inflammatory Peptides Solomonamides A and B: Synthesis of a Macrocyclic Skeleton and Key Fragment 4-Amino-6-(2′-amino-4′-hydroxyphenyl)-3-hydroxy-2-methyl-6-oxohexanoic Acid (AHMOA),"A first synthetic effort toward total synthesis of highly potent solomonamides is disclosed. An efficient strategy to synthesize this class of compounds, along with the synthesis of a core macrocycle (shown in red) and the key fragment AHMOA, is described.",10.1021/ol303149k,2012-12-05,0.6906626435236225
Journal of the American Chemical Society,Total Synthesis of (+)-Macquarimicin A,"The first total synthesis of (+)-macquarimicin A (1), a novel inhibitor of neutral sphingomyelinase (N-SMase) with antiinflammatory activity, has been accomplished. The present work determined the absolute configuration of (+)-1 and revised the C(2)-C(3) geometry to be Z. The synthesis features a transannular Diels-Alder reaction, which constructed the tetracyclic framework stereoselectively, and a convergent and efficient synthetic pathway, which afforded (+)-macquarimicin A (1) in 27 steps (longest linear sequence) with 9.9% overall yield.",10.1021/ja038732p,2003-11-08,0.6906573221082114
Organic Process Research & Development,Process Development of C–N Cross-Coupling and Enantioselective Biocatalytic Reactions for the Asymmetric Synthesis of Niraparib,"Process development of the synthesis of the orally active poly(ADP-ribose)polymerase inhibitor niraparib is described. Two new asymmetric routes are reported, which converge on a high-yielding, regioselective, copper-catalyzed N -arylation of an indazole derivative as the late-stage fragment coupling step. Novel transaminase-mediated dynamic kinetic resolutions of racemic aldehyde surrogates provided enantioselective syntheses of the 3-aryl-piperidine coupling partner. Conversion of the C–N cross-coupling product to the final API was achieved by deprotection and salt metathesis to isolate the desired crystalline salt form.",10.1021/op400233z,2013-10-25,0.6906443059196097
Organic Process Research & Development,Initial Scale-Up and Process Improvements for the Preparation of a Lead Antibacterial Macrolone Compound,"Macrolones are a novel class of potent antimicrobial agents that consist of a macrolide scaffold to which a quinolone unit is tethered by various linkers to the 4′′- O -position of the cladinose sugar. In this paper is described a modified 13-step route to a lead compound in the series. Critical reaction steps in the medicinal chemistry route were modified for an initial scale-up process, and as a result, a synthetic procedure suitable for preparation of multihundred gram quantities of the final product, with 98% purity, has been developed. The new procedure does not require any purification by column chromatography for any of the reaction steps. The overall yield was increased from 5−8% in the medicinal chemistry route to 27% in the improved procedure.",10.1021/op100199t,2010-09-28,0.6906379123865425
Organic Letters,Synthesis of the C22–C40 Domain of the Azaspiracids,An efficient synthesis of the C22-C40 domain of the azaspiracids is described. The synthetic route features a Nozaki-Hiyama-Kishi (NHK) coupling and chelation controlled Mukaiyama aldol reaction to access an acyclic intermediate and a double-intramolecular-hetero-Michael addition (DIHMA) to provide the FG-ring system bridged ketal.,10.1021/acs.orglett.6b00557,2016-04-04,0.6905764509778193
Organic Letters,"A Highly Stereoselective, Efficient, and Scalable Synthesis of the C(1)–C(9) Fragment of the Epothilones","A second-generation synthesis of the C(1)-C(9) fragment of the epothilones is reported. The key tandem intramolecular silylformylation/crotylsilylation/""aprotic"" Tamao oxidation sequence has been redeveloped as a stepwise intermolecular variant, allowing excellent levels of diastereoselectivity in the crotylation step and proceeds in 50% overall yield on gram scale. An improved synthesis of the homopropargyl alcohol starting material is also described, which proceeds in four steps and >99% ee from inexpensive starting materials and is amenable to multigram scales.",10.1021/acs.orglett.5b03034,2015-11-12,0.6905763997317605
Organic Process Research & Development,"Development of a Scalable Synthesis of Casdatifan (AB521), a Potent, Selective, Clinical-Stage Inhibitor of HIF-2α","Casdatifan (AB521) is a potent and selective inhibitor of HIF-2α, currently under clinical evaluation for the treatment of clear cell renal cell carcinoma (ccRCC). Here, we report the development of a scalable synthesis of casdatifan, which was used to support its preclinical characterization and the initiation of phase 1 clinical studies. A convergent approach to assembling the tetracyclic scaffold and the development of efficient routes to key intermediates enabled the successful delivery of material to meet clinical development timelines. Crucial to the efficiency of the synthesis was the strategic design of synthetic routes that leverage a combination of substrate and catalyst control to set each of the 5 stereocenters found in the molecule with exquisite selectivity.",10.1021/acs.oprd.4c00497,2025-02-05,0.6905325736133218
Organic Process Research & Development,Early Development Scale-Up of a Novel CXCR Antagonist: Focus on Racemic and Stereoselective Routes of a Key Intermediate,"Efforts toward a convenient and scalable process for the synthesis of a novel CXCR antagonist 1 are described, with a specific focus on a chiral key intermediate. Two generations of a racemic route have been developed for short-term deliveries, and a stereoselective process has been devised for longer term plans. Key steps involved an enzymatic resolution of racemic tetrahydrothiophene-2-carboxylic acid to install the (2 R ) stereocenter, the mild and efficient preparation of a sterically hindered sulfinimine under a nitrogen flow, and its stereoselective reduction to set up the (1 S ) amine stereocenter. The process has been scaled-up to multikilogram scale for the racemic approach, and the stereoselective route was demonstrated on multigram scale.",10.1021/acs.oprd.7b00325,2017-11-21,0.6905104775176922
Organic Process Research & Development,Practical Synthesis of the High-Quality Antitumor Agent KW-2189 from Duocarmycin B2 Using a Facile One-Pot Synthesis of an Intermediate,"A facile and large-scale preparation process of a potent antitumor agent KW-2189 ( 2 ), derived from the antitumor antibiotic duocarmycin B2 ( 1 ), has been developed. This new synthetic route required three steps: (i) one-pot carbamoylation and subsequent reduction, (ii) Wagner−Meerwein rearrangement of the methoxycarbonyl group for the production of the pyrrole compound 6, and (iii) formation of the hydrobromide salt 2 . The key strategic improvement was to obtain good quality hydroxy compound 4 in a reasonable yield without isolation of the unstable keto intermediate 3a . During commercial-scale production at a scale of about 50 g, this strategy provided high-quality KW-2189 ( 2 ) in a 55% overall yield from 1 . Potential degradation compounds 7 − 9 were also synthesized and shown to be absent in the KW-2189 ( 2 ) prepared.",10.1021/op980038k,1998-08-21,0.6904882165717404
Tetrahedron,"A new synthetic route to 2-(p-nitrobenzyl)-1,4,7,10-tetraazacyclododecane",,10.1016/s0040-4039(00)73873-1,1993-08-01,0.6904792663568871
Synlett,Practical Synthesis of the C-1027 Aminosugar Moiety,A concise and reliable synthetic route to the aminosugar moiety of the C-1027 chromophore was developed. The aminosugar moiety was synthesized from l-glutamic acid in 11 steps and 13% overall yield.,10.1055/s-0030-1258524,2010-07-27,0.6904543139930711
Organic Process Research & Development,Working Toward Process Simplification for the Synthesis of Crisaborole,"The development of a concise synthesis of crisaborole ( 1 ), a phosphodiesterase 4 (PDE4) inhibitor, is described. There are several challenges with the initial commercial synthesis that were drivers for process redesign and simplification, most notably the need for protection/deprotection steps. Key bond disconnections and reordering of steps were evaluated to streamline the process focusing on greener options for manufacture and eliminating protecting groups. The resulting alternate synthesis features a similar Miyaura borylation to install the key boron atom but provides a more direct route to crisaborole through an important crystalline intermediate for impurity purge. Other challenges addressed by the alternate route include avoiding environmentally undesirable reagents DMF and boric acid (both included on the REACH list of substances of very high concern), reducing palladium usage, and eliminating the use of a palladium scavenging treatment. Successful demonstration of the alternate route for crisaborole has been achieved at pilot plant scale and ultimately has been validated at commercial scale consistent with ICH Q11 principles. The route was approved for commercial use to supply crisaborole in 2023 and to date has produced approximately 750 kg of the crisaborole drug substance.",10.1021/acs.oprd.5c00316,2025-11-13,0.6904534745140422
Organic Letters,Total Synthesis of (+)-Aspidospermidine,"A facile asymmetric total synthesis of (+)-aspidospermidine has been developed, which is accomplished in 11 steps in an overall yield of 9.6%. Key steps involve a palladium-catalyzed enantioselective decarboxylative allylation to install the quaternary carbon stereocenter and a highly efficient reductive amination–carbonyl reduction–dehydration–intramolecular conjugate addition cascade to build the cis D-ring.",10.1021/acs.orglett.9b02346,2019-07-29,0.6904469389486301
Synthesis,Synthesis of an Azabicyclo[3.1.0]hexanone-Containing Inhibitor of NF-κΒ Inducing Kinase via Catalytic C–H Activation,"Abstract The synthesis of an azabicyclo[3.1.0]hexanone-containing inhibitor of the nuclear factor-κB inducing kinase (NIK) is reported. The initial route to this compound was streamlined from 13 to 7 linear steps through the use of a catalytic, enantioselective C–H activation step. A procedure for lactam oxidation was identified that avoided use of peroxides on scale. These synthetic improvements allowed for the synthesis of multigram quantities of the desired NIK inhibitor for in vivo profiling.",10.1055/s-0040-1707279,2020-09-15,0.6904385657649588
Organic Process Research & Development,"Development of a Commercial Ready Process for <b>TNG908</b>: A Potent, Selective, and Brain-Penetrant MTA-Cooperative PRMT5 Inhibitor","High Resolution Image Download MS PowerPoint Slide TNG908 is a potent, selective, and brain-penetrant MTA-cooperative PRMT5 inhibitor for the treatment of MTAP -deleted tumors. We describe here the chemical process development for the synthesis of TNG908 and the improvements that were achieved over the medicinal chemistry route with much higher yields and better purities. This commercial ready process is convergent, diastereoselective, safe, reproducible, and robust. A total of eight GMP batches have been successfully manufactured, resulting in high-purity API meeting all specifications.",10.1021/acs.oprd.5c00017,2025-02-20,0.6903483101422653
European Journal of Organic Chemistry,A Stereoselective Synthesis of Dihydrosphingosine,"A highly enantioselective synthesis of D-(+)-erythro-dihydrosphingosine (sphinganine) as its triacetate derivative 10, starting from palmityl alcohol (3) and employing the Sharpless asymmetric dihydroxylation as the key step, is described.",10.1002/1099-0690(200010)2000:20<3447::aid-ejoc3447>3.0.co;2-t,2000-10-01,0.6903338361925292
Journal of Organic Chemistry,"Total Synthesis of SR 121463 A, a Highly Potent and Selective Vasopressin V<sub>2</sub>Receptor Antagonist","SR 121463 A, 1, is a promising nonpeptide prototype for potent and selective antagonism of the vasopressin V(2) receptor subtype and, thus, a candidate for control of the clinically debilitating condition of hyponatremia and its associated syndromes. In the present work, we present a novel and stereoselective synthesis that stems from the preparation of three key intermediates: the substituted benzenesulfonyl chloride 2, the N-protected oxindole 3, and protected dibromide 4. The synthesis of 1 has been achieved in good overall yield, each step proceeding in greater than 80% yield. In addition, intermediate 2 and the syn isomer of 1 were prepared with complete control of stereochemistry. The latter reduction appears to proceed by lithium cation mediated chelation control. Molecular mechanics calculations with the MM3* and MMFF force fields underscore geometric and energetic aspects of the reaction.",10.1021/jo0004658,2001-04-20,0.6903151234741852
Journal of Organic Chemistry,Halichondrin B:  Synthesis of the C1−C22 Subunit,"[Reaction: see text]. Two efficient routes to the C1-C22 subunit of halichondrin B are described. The cage ketal 7, which contains 11 asymmetric centers embedded within the ABCDEF-ring framework, was assembled from (+)-conduritol E (27) in 18 steps and 4% overall yield. In a separate route, 7 was also synthesized in 18 steps and 2% overall yield from a derivative of alpha-d-glucoheptonic acid gamma-lactone (62). While the former route installs the fully elaborated C-ring endowed with the correct C12 stereochemistry early in the synthesis, the latter features a late-stage introduction of the C12 stereocenter during the ultimate one-pot Michael addition/ketalization cascade to form the CDE-ring system of the cage. The importance of the C12 stereocenter to the crucial ketalization event is discussed through comparison of these two strategies.",10.1021/jo051479m,2005-10-15,0.6902771882851775
Synthesis,Practical Synthesis of Enantiomerically Pure 2-(Diphenylphosphanyl)ferrocene Carboxylic Acid,A practical synthesis of both enantiomers of ortho-diphenylphosphanylferrocene carboxylic acid (o-DPPFA) starting from ferrocene is described. Key steps include the synthesis of the racemic title compound from ferrocene in two steps followed by resolution by way of diastereomeric ester formation with glucose diacetonide. The synthesis allows for preparation of gram quantities of both optical antipodes of o-DPPFA (3) in good yields and enantiomerically pure form (>99% ee).,10.1055/s-2005-872111,2005-08-04,0.6902681321609409
Journal of Organic Chemistry,"Efficient Synthesis of [6-Chloro-2-(4-chlorobenzoyl)-1<i>H</i>-indol-3-yl]-acetic Acid, a Novel COX-2 Inhibitor","The synthesis of 6-chloro-2-(4-chlorobenzoyl)-1H-indol-3-ylacetic acid (1), a selective cyclooxygenase 2 (COX-2) inhibitor, is described. The synthesis relied on a novel indole formation that involved an alkylation/1,4-addition/elimination/isomerization cascade. It was demonstrated that the entire sequence from sulfonamide 13 and bromoketone 14 to the desired indole (1) could be executed in a single pot.",10.1021/jo034274r,2003-04-15,0.6901859570633859
Organic Process Research & Development,Development of a Preparative-Scale Asymmetric Synthesis of (<i>R</i>)-<i>p</i>-Tolyl Methyl Sulfoxide for Use in a One-Pot Synthesis of a Drug Intermediate Containing a Trifluoromethyl-Substituted Alcohol Functionality,"A one-pot process for the synthesis of ( S )-1,1,1-trifluoro-4-(5-fluoro-2-methoxy-phenyl)-4-methyl-2-(( R )-toluene-4-sulfinylmethyl)pentan-2-ol ( 3 ) is described, which was a key intermediate for the preparation of a class of novel glucocorticoid receptor ligands. The chemistry features the preparative-scale synthesis of ( R )- p -tolyl methyl sulfoxide [( R )- p TMSO] from (2 R,4 S,5 R )-4-methyl-5-phenyl-3-(tolene-4-sulfonyl)oxathiazolidine-2-oxide ( 5) and the synthesis of 3 from 5 without isolation of ( R )- p TMSO during the process.",10.1021/op700010a,2007-04-17,0.6901801270030065
Tetrahedron,A novel synthetic route to chalcogen substituted diphospholes,,10.1016/s0040-4039(99)00535-3,1999-05-01,0.6901219348626363
Organic Process Research & Development,"Process Development of Sotagliflozin, a Dual Inhibitor of Sodium–Glucose Cotransporter-1/2 for the Treatment of Diabetes","The development of an efficient manufacturing process for sotagliflozin (LX4211), a dual inhibitor of sodium–glucose cotransporter-1/2 (SGLT-1/2) for the treatment of diabetes, is described. Sotagliflozin features five contiguous chiral centers on the carbohydrate core flanked by a thioether group and a biaryl moiety. Three chiral centers are obtained from the starting material l -xylose, while the other two were established (or modified) via three highly stereoselective transformations: Luche reduction (dr: 97/3), dynamic kinetic resolution of anomeric hemiacetal (dr: 95/5), and Lewis acid-promoted thiolation (dr: 1000/1). Global deprotection of the resulting penultimate intermediate with catalytic sodium methoxide followed by recrystallization furnishes sotagliflozin. The longest linear sequence consists of 10 steps from l -xylose with an overall yield of 40%. This process has been performed on multi-hundred kilogram batches to satisfy the drug substance development demands.",10.1021/acs.oprd.0c00359,2020-10-07,0.6900988534938335
Organic Letters,An Efficient Total Synthesis of (−)-Huperzine A,"The total synthesis of Lycopodium alkaloid (-)-huperzine A has been accomplished in 10 steps with 17% overall yield from commercially abundant (R)-pulegone. The synthetic route features an efficient synthesis of 4 via a Buchwald-Hartwig coupling reaction, a dianion-mediated highly stereoselective alkylation of 4, and a rare example of an intramolecular Heck reaction of an enamine-type substrate. The stereoselective β-elimination and the accompanying Wagner-Meerwein rearrangement are of particular interest.",10.1021/ol301951r,2012-08-17,0.6900220788635716
Journal of the American Chemical Society,Catalytic Asymmetric Total Synthesis of (−)-Actinophyllic Acid,"Described herein is a catalytic asymmetric total synthesis of (-)-actinophyllic acid, with the key step being a chiral phosphine-catalyzed [3 + 2] annulation between an imine and an allenoate to form a pyrroline intermediate in 99% yield and 94% ee. The synthesis also features CuI-catalyzed coupling between a ketoester and a 2-iodoindole to shape the tetrahydroazocine ring; intramolecular alkylative lactonization; SmI2-mediated intramolecular pinacol coupling between ketone and lactone subunits to assemble the complex skeleton of (-)-actinophyllic acid; and an unprecedented regioselective dehydroxylation.",10.1021/jacs.6b00567,2016-02-24,0.6900109852169536
Journal of Organic Chemistry,Total Synthesis of Dictyodendrins B and E,"The concise synthesis of the novel telomerase inhibitors dictyodendrins B and E was completed in only 9 and 11 steps (longest linear sequence). The highly convergent strategy employed a palladium-catalyzed Larock indole synthesis and a palladium-mediated one-pot consecutive Buchwald-Hartwig amination/C-H activation reaction as key steps. The present synthesis exhibits respectable levels of atom-, redox-, and step-economy.",10.1021/jo400841d,2013-05-13,0.6899671039570526
Tetrahedron,"Highly efficient two-step selective synthesis of 2,6-dimethylnaphthalene",,10.1016/j.tetlet.2006.08.102,2006-09-19,0.6899277475554426
Organic Process Research & Development,Development of an Efficient Synthesis of an Agonist of Acetylcholine Nicotinic Receptor,A new manufacturing process for N -[[1-(methylamino)cyclopropyl]methyl]pyridine-3-amine hemigalactarate ( 1 ) has been developed. Herein we wish to report the development and optimization of the route using alternative reaction conditions for a reduction/oxidation/reductive amination/protecting group cleavage sequence. Improvement of the crystallization process enabled the production of multikilogram amounts of agonist 1 under cGMP control with a purity of >99.5%. A telescoped process involving 5 steps is also described.,10.1021/acs.oprd.8b00220,2018-08-28,0.6899237190784367
Organic Letters,Total Synthesis of (<i>R</i>)-Sarkomycin Methyl Ester via Regioselective Intermolecular Pauson–Khand Reaction and Iridium-Catalyzed Asymmetric Isomerization,"A new five-step enantioselective synthesis of ( R)-sarkomycin methyl ester is described. The cyclopentane scaffold was built by a regioselective intermolecular Pauson-Khand reaction. Enantioselectivity was introduced by a novel Ir-catalyzed isomerization reaction. The last steps involved a catalytic hydrogenation of the exocylic double bond, followed by the deprotection and elimination of the amino group. This route is the shortest enantioselective synthesis of this antibiotic reported to date.",10.1021/acs.orglett.8b01525,2018-06-15,0.6898692428317387
Organic Letters,A Unified Strategy to <i>Plakortin</i> Pentalenes: Total Syntheses of (±)-Gracilioethers E and F,"A unified route to oxygenated Plakortin pentalenes is described. Along with the previously disclosed total synthesis of hippolachnin A, the potential of this scheme is demonstrated by the first total synthesis of gracilioether E, as well as the total synthesis of gracilioether F. Key features of the unified synthetic strategy include the concise construction of common key intermediate 1 and a topological-strategy guided functionalization of a highly substituted cyclobutene providing efficient access to the core skeletons.",10.1021/acs.orglett.5b03356,2015-12-21,0.6898515446261824
Journal of the American Chemical Society,A Convergent Synthetic Route to (+)-Dynemicin A and Analogs of Wide Structural Variability,"An enantioselective synthetic route to (+)-dynemicin A ( 1 ) is described that involves as the key and final step the Diels−Alder cycloaddition of the quinone imine 6 with the isobenzofuran 107 followed by an oxidative workup to provide (+)- 1 in 40% yield. The synthetic route begins with the condensation of (−)-menthyl acetoacetate and trans -ethyl crotonate to form the crystalline cyclohexanedione 14, which is then transformed to the enantiomerically pure quinone imine 6 in 23 steps with an average yield of 85% and an overall yield of 2−3%. Key features of this sequence include the coupling of the enol triflate 11 and the arylboronic acid 10 (90%), the thermal deprotection/internal amidation of the coupling product 18 (84%), the use of 2-chloropyridine as an economical alternative to 2,6-di- tert -butylpyridine to promote the reaction of the quinolone 9 and triflic anhydride (85%), the highly stereoselective addition of the ( Z )-enediyne 31 to the quinoline 61 (89%), intramolecular acetylide addition within the acetylenic ketone 66 (94%), and oxidation of the phenol 76 with iodosobenzene to afford the quinone imine precursor 77 in 89% yield. Both the quinone imine and isobenzofuran components of the final coupling reaction can be varied, thus providing an ideal route for the preparation of a wide variety of dynemicin analogs.",10.1021/ja9703741,1997-07-01,0.6898283551680108
Organic Letters,Total Synthesis of Scabrolide F,"The first total synthesis of scabrolide F, a norcembranolide isolated from the soft coral Sinularia scabra, is described. Hydroxycarboxylic acid, which is the key synthetic intermediate, was synthesized in a convergent manner by fragment coupling. The obtained hydroxycarboxylic acid was subjected to macrolactonization and subsequent transannular ring-closing metathesis (RCM) to furnish scabrolide F. The synthetic protocol can be extended to the total synthesis of other norcembranolides.",10.1021/acs.orglett.2c03263,2022-10-20,0.6896804091439754
Organic Process Research & Development,Commercial Route Research and Development for SGLT2 Inhibitor Candidate Ertugliflozin,"A practical synthesis of SGLT2 inhibitor candidate ertugliflozin ( 1 ) has been developed for potential commercial application. The highly telescoped process involves only three intermediate isolations over a 12-step sequence. The dioxa-bicyclo[3.2.1]octane motif is prepared from commercially available 2,3,4,6-tetra- O -benzyl- d -glucose, with nucleophilic hydroxymethylation of a 5-ketogluconamide intermediate as a key step. The aglycone moiety is introduced via aryl anion addition to a methylpiperazine amide. High chemical purity of the API is assured through isolation of the crystalline penultimate intermediate, tetraacetate 39 . A cocrystalline complex of the amorphous solid 1 with l -pyroglutamic acid has been prepared in order to improve the physical properties for manufacture and to ensure robust API quality.",10.1021/op4002802,2013-12-21,0.6896594004973134
Journal of Organic Chemistry,"Development of a Two-Step Route to 3-PBC and βCCt, Two Agents Active against Alcohol Self-Administration in Rodent and Primate Models","To gain access to 3-propoxy-β-carboline hydrochloride (3-PBC·HCl) (1·HCl) and β-carboline-3-carboxylate-tert-butyl ester (βCCt) (2), potential clinical agents active against alcohol self-administration, a two-step route was developed. This process involves a palladium-catalyzed Buchwald-Hartwig coupling and an intramolecular Heck reaction. This two-step route provides rapid access to multigram quantities of 3-PBC (1) and βCCt (2), as well as analogues for studies of alcohol self-administration. The overall yield of 3-PBC (1) was improved from 8% to 50% by this route.",10.1021/jo200425m,2011-04-15,0.689633307285859
Organic Process Research & Development,Highly Regioselective Protecting-Group-Free Synthesis of the Antimalarial Drug MMV693183,"High Resolution Image Download MS PowerPoint Slide MMV693183 is a promising antimalarial drug candidate that works for uncomplicated malaria treatment and resistance management. Herein, we report an efficient and highly regioselective synthesis of MMV693183. This novel synthetic method highlights a three-step route with an overall yield of 46% from readily available starting materials. The key to the success lies in (1) utilizing the subtle difference of the two amino groups in the starting material ( S )-propane-1,2-diamine dihydrochloride without amino protection and (2) identifying the L -(+)-tartaric acid as the counter acid for the organic salt formation, yielding the desired regioisomer up to 100:0. The efficient and scalable three-step protocol operates under mild conditions with a high chemo/regioselectivity, providing effective access to MMV693183.",10.1021/acs.oprd.3c00353,2023-12-09,0.6895945967820609
Journal of Organic Chemistry,Convergent Formal Synthesis of Ecteinascidin 743,"A concise formal synthesis of ecteinascidin 743 is described. Key features involve the coupling of the multisubstituted tetrahydroisoquinoline and phenylalaninol moieties via a regio- and stereoselective Pictet-Spengler cyclization as well as the subsequent chemoselective MOM protection of the phenol group, which opens a rapid access to the desirable pentacycle. The synthesis successfully delivered the advanced intermediate with the characteristic macrolactone from sesamol in 23 steps.",10.1021/acs.joc.9b01778,2019-09-16,0.6895397269440956
Organic Process Research & Development,An Intramolecular Diels–Alder Approach to the Isoindolinone Core of AZD8154,"A new route to the isoindolinone core of dual phosphoinositide 3-kinases-γδ inhibitor AZD8154 was required to enable multikilogram supply during development toward first in human (FIH) trials and beyond. Aiming to avoid a problematic benzyl bromide intermediate encountered in the medicinal chemistry synthesis, we report a proof-of-concept convergent route featuring a key intramolecular Diels–Alder aromatization sequence. Critical to the success of this approach was the identification of t BuOK-mediated aromatization conditions, reliant upon an electron-withdrawing sulfone moiety installed at an early stage. More conventional protic acid dehydration/aromatization conditions were unsuccessful, and using the Lewis acid BF 3 ·Et 2 O gave an unexpected sulfone rearrangement product. Overall, the new route proceeded in 38% yield (four-step longest linear sequence) in <10 total steps and was considered viable for further optimization and scale-up.",10.1021/acs.oprd.3c00507,2024-03-13,0.6895314404226863
Organic Process Research & Development,Development of Scalable Processes for the Preparation of 4-(chloromethyl)-1-cyclohexyl-2-(trifluoromethyl)benzene: A Key Intermediate for Siponimod,"This paper presents the development of two generations of routes for the synthesis of the key intermediate 8-Cl of siponimod. The first generation focuses on a cyanation reaction followed by alkaline hydrolysis to introduce the benzoic acid group, replacing the hazardous nucleophilic carboxylation mediated by n -BuLi in the reported manufacturing route. Furthermore, the use of LiAlH 4 for the carboxylic acid reduction is substituted with a milder acid anhydride reduction enabled by NaBH 4 . Overall, the first-generation route demonstrates an 11.6% increase in yield over 8 steps, effectively addressing concerns related to scale-up effects and safety-critical operations. In the second generation, a two-step synthesis involving nickel-catalyzed Kumada–Corriu coupling and Blanc chloromethylation is devised to produce benzyl chloride 8-Cl, starting from the readily available and cost-effective material 1-halo-2-(trifluoromethyl)benzene 9 . The second-generation route is successfully demonstrated at large scales ranging from hundreds to kilo grams, resulting in a remarkable 32.5% yield increase and approximately 65% reduction in process mass intensity for the synthesis of intermediate 8-Cl .",10.1021/acs.oprd.3c00170,2023-07-21,0.6894175887849339
Organic Process Research & Development,"Efficient and Scalable Diastereoselective Synthesis of ((2<i>R</i>,7a<i>S</i>)-2-fluorotetrahydro-1<i>H</i>-pyrrolizin-7a(5<i>H</i>)-yl)methanol Hydrochloride","An efficient large-scale synthesis of 2a ·HCl, a key fragment to several KRAS inhibitors, is described. Optimization to a previously reported racemic route by Merck includes the development of a catalytic exocyclic olefin oxidation using RuCl 3 /NaIO 4, followed by a highly diastereoselective reduction of the resulting ketone. A second-generation approach was then developed. The highlight of this synthesis includes a one-step intramolecular nucleophilic ring cyclization of 35a or 35b via a stable chelate with lithium cation 38 to give a stereoselective product, bicyclic scaffold 36a, with excellent diastereoselectivity and good yields. Consecutive deoxyfluorination followed by the reduction of benzyl ester 37a afforded 2a ·HCl without the need for chiral separation utilized in the first-generation approach.",10.1021/acs.oprd.4c00462,2025-03-11,0.6894021038016233
Organic Process Research & Development,Development of a Multi-Kilogram-Scale Synthesis of AZD1283: A Selective and Reversible Antagonist of the P2Y<sub>12</sub> Receptor,"Ethyl 6-chloro-5-cyano-2-methylnicotinate ( 4 ) was coupled with 4-piperidinecarboxylic acid (isonipecotic acid) in 81% yield to pyridine acid 10 . An amide coupling between 10 and benzylsulfonamide ( 6 ) afforded AZD1283 ( 1 ) in 79% yield using CDI as coupling reagent. The synthesis has been developed and scaled up to 20 kg batches of 1, supporting preclinical and clinical studies. Development work towards 2-chloropyridine 4 and benzylsulfonamide ( 6 ) is included.",10.1021/op400288v,2013-11-13,0.6893890658205478
Tetrahedron,A novel cyclodimerization of 3-methyl-3-butenenitrile. An efficient synthesis of 4-cyanoisophorone,,10.1016/0040-4039(80)80206-1,1980-01-01,0.6893687420899245
Tetrahedron,A novel cylcodimerization of 3-methyl-3-butenenitrile. An efficient synthesis of 4-cyanoisophorone,,10.1016/s0040-4039(01)92499-2,1981-01-01,0.6893687420899245
Tetrahedron,Formal total synthesis of (−)-balanol: a potent PKC inhibitor,,10.1016/j.tetlet.2009.10.120,2009-11-14,0.6893416386125423
Organic Process Research & Development,Optimizing the CHF6523 Isocoumarin Core Scaffold: From the Preclinical Stage to Large-Scale Production,"The structure of the new active pharmaceutical ingredient (API) PI3Kδ inhibitor CHF6523.02, identified for the treatment of exacerbating chronic obstructive pulmonary disease (COPD) in patients, is reported. The described molecule bears an isocoumarin core scaffold, whose synthetic route scalability is critical for API process development and the successful establishment of a multikilogram synthesis route. In this paper, we describe the process research and development work for the isocoumarin scaffold synthetic procedure, exploiting a novel and efficient electrophilic cyclization step, to provide large quantities of the product required to support the API candidate’s clinical studies.",10.1021/acs.oprd.5c00133,2025-06-30,0.6893178731928322
Angewandte Chemie International Edition,Synthesis of the Pluramycins 2: Total Synthesis and Structure Assignment of Saptomycin B,"A concise, highly convergent total synthesis of saptomycin B, a member of the pluramycin class of antitumor antibiotics, is reported. The target compound was assembled from four building blocks (a tricyclic platform, two sugars, and an alkynal) in 15% yield through 10 synthetic operations. The key steps included the regioselective installation of two amino sugars (L-vancosamine and D-angolosamine) on the tricycle and the efficient construction of the tetracyclic skeleton by an aldol reaction followed by formation of the pyranone. The unknown configuration at C14 was assigned as R.",10.1002/anie.201308017,2013-12-16,0.6893080300730007
Tetrahedron,Synthesis of antitumor ansamycins. 2. A formal synthesis of (±)-macbecin I,"Convergent synthesis of (±)-2 a key intermediate in the Merck synthesis of macbecin I (1.), incorporates the chelation-mediated coupling of a lithiated aryl subunit and the γ-hydroxy aldehyde equivalent 8 to establish a critical connective element of the parent ansamycin.",10.1016/s0040-4039(00)97607-x,1990-01-01,0.689278134675862
Synlett,Improved Synthesis of the Pheromone of the Longtailed Mealybug,A short and efficient synthesis of the longtailed mealybug pheromone featuring an Ireland-Claisen rearrangement as the key step is described.,10.1055/s-0030-1258025,2010-08-30,0.689240177809214
Tetrahedron,An asymmetric synthesis of vigabatrin,Enantiomerically pure vigabatrin is available in four steps and 59% overall yield from butadiene monoepoxide.,10.1016/s0040-4039(96)02148-x,1996-12-01,0.6891904428760984
Journal of the American Chemical Society,Total Synthesis of the Chlorinated Pentacyclic Indole Alkaloid (+)-Ambiguine G,"High Resolution Image Download MS PowerPoint Slide Reported herein is the total synthesis of (+)-ambiguine G, the first member of the chlorinated pentacyclic ambiguines to yield to chemical synthesis. The synthesis is accomplished through a convergent strategy that proceeds in 10 steps from ( S )-carvone oxide. Pivotal to the concise route is the successful realization of a [4+3] cycloaddition that conjoins two easily synthesized components of the carbon framework of the natural product. Also featured in the synthesis is the efficient, diastereoselective construction of a key vinylated chloro ketone and the unprecedented, one-pot reduction–elimination–oxidation sequence that transforms an enone to an advanced hydroxylated-diene intermediate.",10.1021/jacs.1c05762,2021-07-19,0.6891880909508836
Tetrahedron,Synthesis of erythro and threo furanoid glycals using 5-endo-trig selenoetherification as key step,,10.1016/s0040-4039(98)02561-1,1999-02-01,0.6891770150064928
Journal of Organic Chemistry,"A Practical and Improved Synthesis of (3<i>S</i>,5<i>S</i>)-3-[(<i>tert</i>-Butyloxycarbonyl)methyl]- 5-[(methanesulfonyloxy)methyl]-2- pyrrolidinone","A practical and improved synthesis of (3S,5S)-3-[(tert-butyloxycarbonyl)methyl]-5-[(methanesulfonyloxy)methyl]-2-pyrrolidinone (1) is described. The key transformations involve a highly efficient reaction sequence consisting of ethoxycarbonylation, alkylation, hydrolysis, and decarboxylation to produce compound 10. The process described herein is practical, robust, and cost-effective, and it has been successfully implemented in a pilot plant to produce a multikilogram quantity of mesylate 1.",10.1021/jo020433f,2002-10-31,0.6891623140955787
Organic Process Research & Development,Preparation of Guanine PDE Inhibitors:  Development of the Common Synthetic Route Strategy. A Case Study,"A single synthetic route, called the chloropurine route, capable of quickly delivering initial kilogram quantities of several chiral as well as achiral guanine phosphodiesterase inhibitors of increasing complexity is described. During the course of this work, unraveling the formation mechanism of chloropurines allowed for the scale-up of the key intermediates. The mechanism for the cyclization of the chiral five-membered amino alcohols and its implication on the enantiomeric purity needed for this step are also described.",10.1021/op030212r,2004-04-03,0.6890514422454075
Organic Process Research & Development,Practical Synthesis of 2-Amino-5-fluorothiazole Hydrochloride,"The first synthesis of 2-amino-5-fluorothiazole hydrochloride is reported from 2-aminothiazole. The synthesis proceeds in 35% overall yield, involves no chromatographic purification, and has been employed to prepare multikilogram quantities of the title compound. The key fluorine-introducing step comprises the reaction of dilithiated 2- tert -butoxycarbonylaminothiazole with N -fluorobenzenesulfonimide.",10.1021/op0502194,2006-02-10,0.6890408805583068
Synthesis,"New Efficient Method for the Synthesis of Chiral 2,2′-Bipyridyl Ligands","An efficient preparation of chiral 2,2′-bipyridines was developed. Compound 1 was synthesized in 54% yield for three steps starting from 2,6-dibromopyridine. In this synthesis, only catalytic amounts of metals were used in the asymmetric reduction and homo-coupling reaction steps. The total yield and simplicity of experimental procedures were much improved compared with those of the previous report. Other chiral 2,2′-bipyridines were similarly synthesized with high efficiency.",10.1055/s-2005-869983,2005-06-27,0.6889921075839315
Synlett,"Novel Asymmetric Synthesis of an Indolizidine Alkaloid, (+)-Lentiginosine Employing Highly Stereoselective Hydrogenation of α-Hydroxypyrrolidine","All articles of this category An efficient and novel process is described for the asymmetric synthesis of a ( 1S , 2S , 8aS )-dihydroxyindolizidine alkaloid, (+)-lentiginosine in which the asymmetric deoxygenation of the quaternary α-hydroxypyrrolidine derivative derived from D-xylose is used as a key step. indolizidine alkaloid - (+)-lentiginosine - deoxygenation - α-hydroxypyrrolidine - xylose",10.1055/s-1998-1617,1998-02-01,0.6889611830152366
Tetrahedron,A new one-step synthesis of β-carbolines.,,10.1016/s0040-4039(01)93633-0,1979-01-01,0.6889482659855294
Synthesis,A New One-Step Synthesis of Monobromocyclopropanes,,10.1055/s-1972-21853,1972-01-01,0.6889482659855294
Tetrahedron,"A new, one-step synthesis of 1-heteroaryl-2-alkylaminoethanols",,10.1016/j.tetlet.2009.12.021,2009-12-12,0.6889482659855294
Tetrahedron,A new two-step synthesis of 1-arylnaphthalene lignans from cyanohydrins,,10.1016/s0040-4039(00)97879-1,1990-01-01,0.6889482659855294
Tetrahedron,A new one-step synthesis of aziridines from oxiranes,,10.1016/s0040-4039(00)92560-7,1976-10-01,0.6889482659855294
Tetrahedron,Practical and efficient synthesis of N-fused tricyclic indoles,,10.1016/j.tetlet.2010.10.155,2010-11-05,0.6889353600580475
Tetrahedron,A practical and efficient synthesis of (±)- camptothecin,,10.1016/s0040-4039(98)01415-4,1998-09-01,0.6889353600580475
Journal of Organic Chemistry,"Scalable Synthesis and Isolation of the Four Stereoisomers of Methyl 1-Amino-3-(4-bromophenyl)cyclopentanecarboxylate, Useful Intermediates for the Synthesis of S1P1 Receptor Agonists","The individual isomers of methyl 1-amino-3-(4-bromophenyl)cyclopentanecarboxylate are useful intermediates for the synthesis of S1P1 receptor agonists. Herein we describe a scalable synthesis and isolation of each of the four stereoisomers of this compound in gram quantities with >98% ee and de. The utility of this approach is demonstrated by the synthesis of ((1R,3R)-1-amino-3-(4-octylphenyl)cyclopentyl)methanol in 7 steps, 11% overall yield, and >98% ee and de.",10.1021/jo900376b,2009-06-02,0.6889325948787681
Organic Process Research & Development,Process Development of a Potent Bradykinin 1 Antagonist,"As part of Merck’s continued research effort on inflammation and pain, a safe synthesis of an orally bioavailable and CNS penetrant bradykinin 1 antagonist was developed and demonstrated on kilogram scale. The key step included a novel regioselective metal−halogen exchange reaction on 1,2-dibromo-5-chloro-3-fluorobenzene using isopropyl magnesium chloride to install the 1,2,4-oxadiazole ring structure. Suzuki cross-coupling reaction between a highly functionalized and sterically hindered electrophile and boronic ester generated the biaryl ring system, which was converted to the target molecule ( 1 ) using standard chemistry. The safe installation of a 1,2,4-oxadiazole ring proved to be challenging since the original synthetic route relied on the preparation of a highly functionalized benzonitrile using potassium cyanide and resulted in low yields and large amounts of potentially hazardous waste. Overall, a safe and robust synthesis was developed, which occurred in eight linear steps with an overall yield of 28%.",10.1021/op8003184,2009-03-06,0.6889152098482183
Journal of Organic Chemistry,"Practical Synthesis of PC190723, an Inhibitor of the Bacterial Cell Division Protein FtsZ",A high-yielding and practical synthesis of the bacterial cell division inhibitor PC190723 is described. The synthesis is completed in a longest linear sequence of five steps from commercially available starting materials and can be readily executed on a multigram scale.,10.1021/jo101720y,2010-10-29,0.6888602379722153
Organic Process Research & Development,"An Efficient and Scalable Synthesis of the Endothelin Antagonists UK-350,926 and UK-349,862 Using a Dynamic Resolution Process","The development and scale-up of a potential manufacturing route to the endothelin antagonists UK-350,926 1 and UK-349,862 2 are described. A key synthetic challenge in designing an efficient route to these molecules was the optical lability of the stereogenic centre during the construction of the acylsulfonamide functionality. In the discovery synthesis of UK-350,926 the chiral centre was introduced by classical resolution and the acylsulfonamide functionality synthesized by construction of the N -sulfonyl bond. An alternative more efficient process route was developed involving the preparation of racemic UK-350,926 and final step dynamic resolution with ( S )-(−)-1-phenylethylamine as the key step. The process route prepared the acylsulfonamide by construction of the N -carbonyl bond, eliminates a cryogenic reaction and a hazardous intermediate from the synthesis, improves the overall process yield, and allows access to both endothelin antagonists from common intermediates without the need for purification by chromatography. Full experimental details of the new five-step process to prepare UK-349,862 from commercially available starting materials are given for the first time.",10.1021/op050102f,2005-08-19,0.6888520334996124
Synthesis,An Improved Synthesis of Arylphenylamines,,10.1055/s-1974-23466,1974-01-01,0.6888414879823873
Tetrahedron,An improved synthesis of (±)-dihydroactinidiolide,,10.1016/s0040-4039(00)93483-x,1991-09-01,0.6888414879823873
Tetrahedron,"An improved synthesis for N,N′-thiocarbonyl-diimidazole",,10.1016/s0040-4039(00)90762-7,1967-01-01,0.6888414879823873
Tetrahedron,An improved synthesis of pavinanes,,10.1016/s0040-4039(01)87054-4,1973-01-01,0.6888414879823873
Tetrahedron,An improved synthesis of diiodonoradamantane,,10.1016/j.tetlet.2009.08.108,2009-09-03,0.6888414879823873
Tetrahedron,An improved synthesis of monoazaporphyrins,,10.1016/0040-4039(95)00089-u,1995-03-01,0.6888414879823873
Tetrahedron,Improved synthesis of oligodeoxyribonucleotides,,10.1016/0040-4039(90)80122-3,1990-01-01,0.6888414879823873
Tetrahedron,An improved synthesis of the C42–C52 segment of ciguatoxin 3C,,10.1016/j.tetlet.2018.02.052,2018-02-21,0.6888414879823873
Synthesis,An Improved Synthesis of γ-Crotonolactone (2-Buten-4-olide),,10.1055/s-1974-23235,1974-01-01,0.6888414879823873
Synlett,"Improved Synthesis of 5,5′′-Dibromo-2,2′ : 6′,2′′-terpyridine",International audience,10.1055/s-2002-19767,2002-01-01,0.6888414879823873
Tetrahedron,2-Ethynylperylene and improved synthesis of 3-ethynylperylene,,10.1016/j.tetlet.2016.01.067,2016-01-20,0.6888414879823873
Synthesis,"An Improved Synthesis of γ-, δ-, and ε-Lactams",,10.1055/s-1978-24834,1978-01-01,0.6888414879823873
Tetrahedron,An improved synthesis of cyclopropanols,,10.1016/s0040-4039(00)93109-5,1976-10-01,0.6888414879823873
Synthesis,"An Improved Synthesis of 1,4-Diynes",,10.1055/s-1979-28653,1979-01-01,0.6888414879823873
Tetrahedron,An improved synthesis of 6-O-monotosyl-6-deoxy-β-cyclodextrin,,10.1016/s0040-4039(98)00417-1,1998-05-01,0.6888414879823873
Synthesis,"An Improved Synthesis of 2,6-Diarylphenols",,10.1055/s-1982-29734,1982-01-01,0.6888414879823873
Synthesis,An Improved Synthesis of Tetraphenylcyclobutadieneiron Tricarbonyl,,10.1055/s-1971-35044,1971-01-01,0.6888414879823873
Tetrahedron,An improved synthesis of tetramethylcyclopentadiene,,10.1016/s0040-4039(00)77144-9,1994-04-01,0.6888414879823873
Tetrahedron,An improved synthesis of 2′-azido-2′-deoxyuridine,,10.1016/s0040-4039(00)78425-5,1994-11-01,0.6888414879823873
Synthesis,An Improved Synthesis of Cyclooctyne,,10.1055/s-1978-24725,1978-01-01,0.6888414879823873
Tetrahedron,An improved synthesis of 3-aminoestrone,,10.1016/j.tetlet.2005.08.105,2005-09-09,0.6888414879823873
Synthesis,An Improved Synthesis of Monoisopinocampheylborane,,10.1055/s-1978-24695,1978-01-01,0.6888414879823873
Synthesis,An Improved Synthesis of Cyanotrimethylsilane,,10.1055/s-1982-29804,1982-01-01,0.6888414879823873
Tetrahedron,Improved synthesis of (R)-7-hydroxycarvone from (S)-α-pinene,,10.1016/j.tetlet.2013.10.066,2013-10-23,0.6888414879823873
Tetrahedron,An improved synthesis of isonitrosoacetanilides,,10.1016/j.tetlet.2005.10.046,2005-10-28,0.6888414879823873
Synthesis,An Improved Synthesis of Cannabinol and Cannabiorcol,,10.1055/s-1981-29671,1981-01-01,0.6888414879823873
Tetrahedron,An improved synthesis of tetramesitylporphyrin,,10.1016/s0040-4039(00)96287-7,1987-01-01,0.6888414879823873
Tetrahedron,An improved synthesis of iodohydrins from alkenes,,10.1016/s0040-4039(99)02022-5,2000-01-01,0.6888414879823873
Tetrahedron,An improved synthesis of [2.2.3]cyclazines from 3-pyrrolizines,,10.1016/s0040-4039(00)87230-5,1982-01-01,0.6888414879823873
Tetrahedron,A much improved synthesis of the siderophore enterobactin,,10.1016/s0040-4039(96)02452-5,1997-02-01,0.6888414879823873
Tetrahedron,"Improved modular synthesis of thieno[3,2-b]pyrroles and thieno[2,3-b]pyrroles",,10.1016/j.tetlet.2009.01.109,2009-01-24,0.6888414879823873
Synthesis,An Improved Synthesis of 2-Alkynyl Sulfides,,10.1055/s-1979-28858,1979-01-01,0.6888414879823873
Synthesis,Octamethylnaphthalene (Improved Synthesis) and Octamethylbiphenylene,,10.1055/s-1979-28796,1979-01-01,0.6888414879823873
Synthesis,An Improved Synthesis of Propynal,,10.1055/s-1980-29052,1980-01-01,0.6888414879823873
Tetrahedron,An improved synthesis of glycinamide ribonucleotide,,10.1016/s0040-4039(00)99530-3,1989-01-01,0.6888414879823873
Tetrahedron,An improved synthesis of Lu AA20465,,10.1016/j.tetlet.2006.05.117,2006-06-11,0.6888414879823873
Tetrahedron,Improved synthesis of monodentate and bidentate 2- and 3-pyridylphosphines,,10.1016/j.tetlet.2007.02.127,2007-03-06,0.6888414879823873
Tetrahedron,An improved synthesis of releasable luciferin–CPP conjugates,,10.1016/j.tetlet.2009.06.038,2009-06-12,0.6888414879823873
Tetrahedron,An improved synthesis of corrole,,10.1016/s0040-4039(97)00839-3,1997-06-01,0.6888414879823873
Tetrahedron,Improved synthesis of C8–C20 segment of pectenotoxin-2,,10.1016/j.tetlet.2011.08.051,2011-08-25,0.6888414879823873
Tetrahedron,An improved synthesis of the octalactins,,10.1016/0040-4039(95)01493-2,1995-10-01,0.6888414879823873
Tetrahedron,Improved synthesis of a C3-symmetrical pyridinophane,,10.1016/j.tetlet.2008.01.077,2008-01-21,0.6888414879823873
European Journal of Organic Chemistry,Biogenetically Inspired Total Synthesis of (+)‐Liphagal: A Potent and Selective Phosphoinositide 3‐Kinase α (PI3Kα) Inhibitor from the Marine Sponge <i>Aka coralliphaga</i>,"Abstract A biologically attractive and structurally unique marine natural product, (+)‐liphagal, was biomimetically synthesized in 29 % overall yield in a longest linear sequence of 13 steps from commercially available (+)‐sclareolide. This synthesis involved the following crucial steps: (i) stereocontrolled hydrogenation of an endo ‐olefinic decalin to install the C8 stereogenic centre present in the requisite decalin segment; (ii) coupling of the decalin segment with an aromatic moiety to assemble the desired carbon skeleton; (iii) ring expansion of a proposed biogenetic intermediate followed by benzofuran formation to establish the requisite tetracyclic core structure. A few new aspects of the proposed biosynthetic pathway to this class of natural products were revealed.",10.1002/ejoc.201402082,2014-04-17,0.6888035706951595
Organic Process Research & Development,"Practical Diastereoselective Synthesis and Scale-up Study of (+)-2-((1<i>R</i>,2<i>R</i>,3<i>R</i>,5<i>S</i>)-2-Amino-6,6-dimethylbicyclo[3.1.1]hept-3-yl)ethanol: A Key Intermediate of the Novel Prostaglandin D<sub>2</sub>Receptor Antagonist S-5751","A new synthetic process was developed for (+)-2-((1 R,2 R,3 R,5 S )-2-amino-6,6-dimethylbicyclo[3.1.1]hept-3-yl)ethanol, a key intermediate of S-5751. Diastereoselective alkylation of (+)-nopinone with ethyl bromoacetate, formation of O -methyl oxime, and diastereoselective reduction with NaBH 4 −AlCl 3 could be safely carried out. Stereochemistry of the (1 R,2 R,3 R,5 S )-6,6-dimethylbicyclo[3.1.1]heptane ring was discussed to achieve high diastereoselectivity on these reactions. For the scale-up, detailed consideration was given to the safety of the NaBH 4 −AlCl 3 reduction.",10.1021/op9001092,2009-07-02,0.6887952197600871
Tetrahedron,"A practical method for multigram scale synthesis of (+)-methyl 5(S),6(R)-epoxy-6-formylhexanoate and 2(R),3(S)-epoxyoctanal, key intermediates for synthesis of leukotrienes A4",,10.1016/s0040-4039(00)85062-5,1986-01-01,0.6887855082561184
Journal of Organic Chemistry,"Development of a New and Practical Route to Chiral 3,4-Disubstituted Cyclopentanones:  Asymmetric Alkylation and Intramolecular Cyclopropanation as Key C−C Bond-Forming Steps",An efficient and practical asymmetric synthesis of (+)-trans-3-hydroxymethyl-4-(3-fluorophenyl)cyclopentanone (1) is described. An asymmetric Mo-catalyzed alkylation reaction was used to establish the first stereocenter and a Cu-catalyzed intramolecular diastereoselective cyclopropanation reaction was used to set the second stereocenter. The last step involved a one-pot ring-opening/deprotection/hydrolysis/decarboxylation sequence that furnished the desired product in good yield.,10.1021/jo025890a,2002-07-19,0.6887629068790052
Organic Process Research & Development,"New Procedure for the Preparation of (<i>Z</i>)-2-(5-Amino-1,2,4-thiadiazole-3-yl)-2-trityloxyiminoacetic Acid","A novel and efficient procedure has been developed for the preparation of the C-7 side chain of ceftobiprole, ( Z )-2-(5-amino-1,2,4-thiadiazole-3-yl)-2-trityloxyiminoacetic acid ( 2 ) from malononitrile ( 9 ) in a total yield of 19%. The key intermediate N -(3-(2-acetamido-2-oxoethyl)-1,2,4-thiadiazol-5-yl)benzamide ( 15b ) was synthesized for the first time in 76% yield by treatment of N -(3-aminoisoxazol-5-yl)acetamide ( 13 ) with benzoyl isothiocyanate. More importantly, ( Z )- N -(3-(2-acetamido-2-oxo-1-(trityloxyimino)ethyl)-1,2,4-thiadiazol-5-yl)benzamide ( 16b ) was prepared from 15b with high stereoselectivity and good yield via successive oximation and protection of oxime hydroxy group. The process has a good prospect for industrial synthesis.",10.1021/op100323b,2011-03-28,0.6887279958985639
Journal of Organic Chemistry,Synthesis of the Sex Pheromone of the Oleander Scale (<i>Aspidiotus nerii</i>),"A total synthesis of the oleander scale [ Aspidiotus nerii (Bouche)] sex pheromone, the unique sesquiterpenoid containing a cyclobutane moiety of this class of compounds, has been developed. In order to implement this sex pheromone as a new environmentally friendly tool to manage this pest, a more cost-effective, multigram synthesis was required. This new synthetic route, having a Blaise reaction, iron-catalyzed carbon-carbon coupling, and [2 + 2] photocycloaddition reactions as key steps, provides a general access to 4-alkyl lactones as well as a robust access to the target sex pheromone. Starting from readily available compounds as 3-hydroxypropanenitrile, ethyl bromoacetate, and 2-acetyl butyrolactone, the synthetic sequence afforded the A. nerii sex pheromone with minimum intermediate purification and good overall yield in nine linear steps.",10.1021/acs.joc.9b01001,2019-06-04,0.6886785778245541
Synthesis,"A Short and Efficient Synthesis of 2R,3R,4R-3,4-Dihydroxyproline, 1,4-Dideoxy-1,4-imino-l-xylitol, 2R,3R,4R,5S-3,4,5-Trihydroxypipecolic Acid, and 1,5-Dideoxy-1,5-imino-l-iditol","All articles of this category The syntheses of pyrrolidine alkaloids (-)- 1 and (+)- 3 were accomplished in 47% and 60% overall yield from 2-azido-2-deoxy-l-idonate 5 , while piperidine alkaloids (-)- 2 and (+)- 4 were obtained in 51% and 53% overall yield from the same starting material. Key step includes iodine promoted one-pot cyclization, and selective deprotection of isopropylidene and 9-phenylfluoren-9-yl (Pf) group. carbohydrates - iodine - amino acids - one-pot cyclization - azasugars - protecting group",10.1055/s-2000-6408,2000-01-01,0.6886731762365049
Synlett,Towards Waltheriones C and D: Synthesis of the Oxabicyclic Core,"A route to the oxabicyclic cores of the HIV cytoprotective quinolone alkaloids, waltheriones C and D, is described. The approach relies on a stereospecific transannular bromoetherification followed by reductive debromination. The route can also be rendered enantioselective via enzymatic reduction of a key intermediate (&gt;99:1 er).",10.1055/s-0036-1588150,2017-02-24,0.6885775403227115
Journal of Organic Chemistry,An Efficient Preparation of the Pseudopeptide Endothelin-B Receptor Selective Antagonist BQ-788,,10.1021/jo00130a028,1995-12-01,0.6885647505600879
Tetrahedron,An expeditious chiral route to analogs of mevinolin and compactin,,10.1016/s0040-4039(01)80835-2,1985-01-01,0.6885579605110306
Organic Letters,Studies toward the Total Synthesis of Scyphostatin:  First Entry to the Highly Functionalized Cyclohexenone Segment,"The cyclohexenone segment 2 of scyphostatin (1), a potent inhibitor of neutral sphingomyelinase, was synthesized in an enantioselective manner starting from the bromo ether 5 and D-serinal derivative 3. The synthetic method features a coupling reaction of 5 with 3 to construct the asymmetric quaternary carbon center and a stereospecific epoxide ring formation as the key steps.",10.1021/ol015873s,2001-05-01,0.6885556638889638
Synlett,"Enantioselective Synthesis of the Sex Pheromone of Lichen Moth, Miltochrista calamine, and Its Diastereomer","Abstract The synthesis of a Miltochrista calamine sex pheromone and its diastereomer has been developed. The key steps of the synthetic approach involved Evans’ chiral auxiliaries and the addition of alkyne to aldehyde, which were firstly applied to prepare this sex pheromone and its diastereomer. The synthetic sex pheromone could be used to trap insects and study physiological and ecological questions of the lichen moth.",10.1055/s-0040-1719835,2021-09-22,0.688530353635808
Synthesis,"New Route to Dimethylnaphthalenes Involving Cyclization of Ylidenemalonodinitriles and Ethyl Ylidenecyanoacetates; Part 1. Synthesis of 1,2-, 1,6-, and 2,7-Dimethylnaphthalenes",,10.1055/s-1983-30405,1983-01-01,0.6884815033118945
Synlett,Chemoenzymatic and Chemical Routes to the Nonproteinaceous Amino Acid Albizziine and Its Amide Derivative,"A two-step route for the synthesis of albizziine from N(alpha)-Boc-asparagine which proceeds in 65% overall yield is disclosed. A high-yielding, six-step route for the synthesis of its protected amido derivative gives rapid access to a key component of the complex aminopolyol natural product, zwittermicin A.",10.1055/s-2008-1042756,2008-02-12,0.6884357448010865
Organic Letters,"Total Synthesis of Aplysiasecosterols A and B, Two Marine 9,11-Secosteroids","The total synthesis of aplysiasecosterols A and B has been accomplished. Key features of the synthesis include the Suzuki-Miyaura coupling of each AB-ring segment and common D-ring segment. The AB-ring segment of aplysiasecosterol B was synthesized by Shi asymmetric epoxidation as a key reaction. The common D-ring segment was constructed by stereoselective hydrogenation and Sharpless asymmetric dihydroxylation as key reactions. This late-stage convergent synthesis, which has rarely been reported in secosteroid synthesis, can be adapted to many 9,11-secosteroids.",10.1021/acs.orglett.3c01692,2023-06-14,0.6884153785208199
Tetrahedron,A practical synthetic route to 4′-alkylaristeromycin derivatives: 4′-methylaristeromycin,,10.1016/j.tetlet.2006.03.188,2006-05-05,0.6884057177196126
Journal of Organic Chemistry,Total Synthesis of (+)-18-<i>epi</i>-Latrunculol A: Development of a Synthetic Route,"The evolution of an enantioselective total synthesis of (+)-18-epi-latrunculol A, a congener of the marine-sponge-derived latrunculins A and B, is reported. Key steps include a late-stage Mitsunobu macrolactonization to construct the 16-membered macrolactone, a mild Carreira alkynylation to unite the northern and southern hemispheres, a diastereoselective, acid-mediated δ-hydroxy enone cyclization/equilibration sequence, and a functional-group-tolerant cross-metathesis to access the enone cyclization precursor.",10.1021/jo501733m,2014-09-22,0.6883682239414198
Organic Letters,Total Synthesis of (±)-Powelline and (±)-Buphanidrine,The total synthesis of (+/-)-powelline (13 linear steps in an overall yield of 6%) and (+/-)-buphanidrine (14 linear steps and a 6% overall yield) and has been achieved using a novel approach to the crinane skeleton. An organocatalytic oxidative coupling allowed direct construction of the key quaternary carbon-to-aryl bond in high yield allowing rapid access to the target alkaloids.,10.1021/ol1000654,2010-02-22,0.6883510613236489
Angewandte Chemie International Edition,Total Synthesis and Stereochemical Reassignment of Mandelalide A,"The total synthesis of the tunicate metabolite mandelalide A and the correction of its originally assigned stereochemistry are reported. Key features of the convergent, fully stereocontrolled route include the use of a Prins cyclization for the diastereoselective construction of the tetrahydropyran subunit, Rychnovsky-Bartlett cyclization for the preparation of the tetrahydrofuran moiety, Suzuki coupling, Horner-Wadsworth-Emmons macrocyclization, and glycosylation to append the L-rhamnose-derived pyranoside.",10.1002/anie.201403542,2014-05-18,0.6882571672415858
Organic Process Research & Development,A Scalable Synthesis of the Thromboxane Receptor Antagonist 3-{3-[2-(4-Chlorobenzenesulfonamido)ethyl]-5-(4-fluorobenzyl)phenyl}propionic Acid via a Regioselective Heck Cross-Coupling Strategy,"A regioselective Heck cross-coupling strategy is presented for the large-scale preparation of the thromboxane receptor antagonist 3-{3-[2-(4-chlorobenzenesulfonamido)ethyl]-5-(4-fluorobenzyl)phenyl}propionic acid ( 1 ). Commercially available 3-bromo-5-iodobenzoic acid was first converted to the corresponding acid chloride, and this was then condensed with 4-fluorobenzene via a Friedel−Crafts acylation reaction to give 3-bromo-5-iodophenyl 4-fluorophenyl ketone. Regioselective cross-coupling with ethyl acrylate and then N -vinylphthalimide, each under phosphine-free Heck conditions, led to formation of ethyl 3-[3-(4-fluorobenzoyl)-5-(2-phthalimidovinyl)phenyl]propenoate. Reduction of the benzophenone moiety and saturation of the olefin double bonds, followed by phthalimide ring cleavage, then gave ethyl 3-[3-(2-aminoethyl)-5-(4-fluorobenzyl)phenyl]propionate monocitrate salt. This was converted to the sulfonamido-substituted arylpropionic acid 1 via a two-step one-pot procedure in which sulfonamide formation was achieved via condensation with 4-chlorobenzenesulfonyl chloride, followed by ethyl ester saponification. The route described avoids hazards identified with the original medicinal chemistry based synthesis and allows bulk quantities of drug substance to be produced for toxicological and clinical trials.",10.1021/op970060y,1998-02-24,0.6882499008445263
Tetrahedron,"Efficient formation of 4,6-disubstituted pyrrolo[2,3-d]pyrimidines: a novel route to TWS119, a glycogen synthase kinase-3β inhibitor",,10.1016/j.tetlet.2010.05.032,2010-05-13,0.688226978503747
Organic Letters,Concise Total Synthesis of (±)-Dasyscyphin D,The first and efficient total synthesis of (±)-dasyscyphin D was achieved in 9 steps with 22.6% overall yield. The key steps involved a PtCl(2)-catalyzed pentannulation reaction and acid-catalyzed double Robinson annulations.,10.1021/ol201047m,2011-05-11,0.6882254739714939
Journal of the American Chemical Society,Enantioselective Total Synthesis of Semperoside A,"A versatile and concise strategy has been developed (Scheme 1) for the enantioselective synthesis of semperoside A 1 which is endowed with an unusually glucosylated iridane structure. The crucial step was a Hg(II)-mediated electrophilic heteroatom cyclization of beta-glucoside 4 that readily led to the iridane skeleton while installing the C-2 and C-3 stereocenters with complete stereocontrol. This expeditious route is unprecedented among synthetic approaches to iridoid glycosides and smoothly overcomes the hemiacetals glucosidation issue. The present inaugural total synthesis of semperoside A was achieved in 10 steps and 17% overall yield from the enantiomerically pure lactone 8, thus proving the absolute stereochemistry of 1 unequivocally.",10.1021/ja0493796,2004-04-01,0.6882084855059737
Organic Process Research & Development,"Development and Scale-Up of 7-COOH CBD Synthesis, a Key Cannabinoid Metabolite","This article describes the process development required for the manufacture of a cannabidiol (CBD) metabolite, 7-carboxy cannabidiol (7-COOH CBD), starting from ∼0.5 mT of CBD. A laboratory-scale synthetic route to 7-COOH CBD was not scalable, primarily due to the reliance on chromatography. The route was shortened from 9 to 7 steps by altering the protecting group strategy. Byproduct formation was a major hurdle toward developing a robust process as was identifying points of purification. Chromatography was circumvented, and purification was achieved through base washes, resin treatment, dicyclohexylamine (DCHA) salt formation, and methanol slurry at the final step. Overall, a scalable process was developed for the conversion of CBD to 7-COOH CBD, with pilot-scale manufacturing processing of 30 kg of CBD delivering 1.99 kg of 7-COOH CBD. Further scaling was carried out to deliver 31.79 kg of 7-COOH CBD starting from ∼0.5 mT of CBD.",10.1021/acs.oprd.4c00093,2024-05-15,0.6881908842151564
Tetrahedron,An Efficient Catalytic Stereoselective Route to a Key Intermediate for the Synthesis of the Long-Lived PGI2 Analog ZK 96480 (CicaprostTM),,10.1016/s0040-4039(97)01803-0,1997-10-01,0.6881643879332644
Organic Letters,Total Synthesis of (−)-Salinosporamide A,"A concise and stereoselective total synthesis of (-)-salinosporamide A (1), a potent inhibitor of the 20S proteasome that is in clinical development as an anticancer drug candidate, has been accomplished in 14 steps with 19% overall yield from 4-pentenoic acid. Our synthesis features a stereoselective alkylation utilizing a chiral auxiliary, formation of a pyrrolidine unit, and oxidation of the pyrrolidine to a γ-lactam. To demonstrate the scalability of our synthesis, (-)-salinosporamide A has been synthesized on a gram scale.",10.1021/ol200886j,2011-05-17,0.6881621430289333
Journal of Organic Chemistry,Convergent and Scalable Synthesis of the ABCDE-Ring Fragment of Caribbean Ciguatoxin C-CTX-1,"Convergent and scalable synthesis of the ABCDE-ring fragment of Caribbean ciguatoxin C-CTX-1, the major causative toxin for ciguatera poisoning in the Caribbean Sea and the Northeast Atlantic areas, is described in detail. The key features of the synthesis include an iterative use of 2,2,6,6-tetramethyl piperidine 1-oxyl (TEMPO)/PhI(OAc) 2 -mediated oxidative lactonization and Suzuki–Miyaura coupling en route to the DE-ring system and a convergent fragment coupling to form the ABCDE-ring skeleton via the Suzuki–Miyaura coupling strategy.",10.1021/acs.joc.2c02414,2022-12-20,0.6881492744483967
European Journal of Organic Chemistry,A Concise Synthesis of Mupirocin H Using a Cross‐Metathesis‐Based Strategy,"Abstract A highly efficient (10.1 % overall yield) and convergent (longest linear sequence of 16 steps) synthesis of mupirocin H has been achieved, starting from commercially available (+)‐( R )‐Roche ester. The route relies on an efficient Grubbs cross‐metathesis reaction to generate a key, late‐stage E ‐olefin intermediate, and a cobalt‐catalysed diastereoselective Reformatsky reaction to produce a β‐hydroxy ester that serves as a late‐stage intermediate.",10.1002/ejoc.201402442,2014-07-11,0.6881317654572263
Organic Process Research & Development,A Scalable Synthesis of the INOS Inhibitor PHA-399733,This contribution describes a scalable synthesis of the INOS inhibitor PHA-399733 using the Bucherer−Bergs hydantoin synthesis to introduce the amino acid function.,10.1021/op8002745,2009-02-12,0.6881209457095739
Angewandte Chemie International Edition,"A Synthetic Route to the Saxitoxin Skeleton: Synthesis of Decarbamoyl α‐Saxitoxinol, an Analogue of Saxitoxin Produced by the Cyanobacterium <i>Lyngbya wollei</i>","Pick your poison: Salient features of a concise synthetic route for the saxitoxin skeleton are a bromonium-ion-initiated cascade cyclization of readily prepared 1 to give tricyclic intermediate 2 and the transformation of the gem-dibromomethylene group into an enol acetate unit. This new route enabled the preparation of 3, a naturally occurring analogue of saxitoxin. Cbz=benzyloxycarbonyl, Ms=methanesulfonyl, Py=pyridine.",10.1002/anie.201102494,2011-06-17,0.6881138514241716
Journal of Organic Chemistry,"Synthesis of the Antifungal β-1,3-Glucan Synthase Inhibitor CANCIDAS (Caspofungin Acetate) from Pneumocandin B<sub>0</sub>","A novel three-step synthesis of the highly functionalized antifungal agent CANCIDAS (caspofungin acetate, 2) is described, starting from the natural product pneumocandin B0 (1). The highlights of the synthesis include a stereoselective formation of a phenylthioaminal, a remarkable chemoselective, high-yielding, one-step borane reduction of a primary amide, and a stereoselective substitution of the phenylthioaminal with ethylenediamine producing 2 in a 45% overall yield.",10.1021/jo062008i,2007-03-01,0.6880579451455698
Organic Process Research & Development,Optimization and Scale-Up of an Asymmetric Route to the LTB<sub>4</sub> Inhibitor Ontazolast,"An efficient asymmetric synthesis of the LTB 4 inhibitor Ontazolast is described. Commercially available ( S )-α-pinene, which contains a 93.5% enantiomeric excess (ee) of the desired isomer, can be oxidized using phase-transfer conditions to the corresponding ( R )-hydroxy ketone. Condensation of this keto alcohol with 2-(aminomethyl)pyridine provides an intermediate imine that can be alkylated with cyclohexylmethyl bromide or iodide. The alkylation proceeds with nearly complete transfer of chirality under mild conditions. Cleavage of the chiral auxiliary and isolation of the resulting ( S )-pyridylamine by crystallization with l -tartaric acid furnishes the key amine building block in >99% ee and in excellent overall yield. The tartrate salt is then directly converted to the final product. The reaction sequence is described on a multigram scale.",10.1021/op9701090,1997-09-01,0.6880203642205556
Journal of Organic Chemistry,Studies on the Synthesis of the Alkaloid (−)-Gilbertine via Indolidene Chemistry,"A synthesis route to the pentacyclic alkaloid (-)-gilbertine, which features a cyclization cascade passing through a transient indolidene intermediate, was pursued. A key stereochemical relationship was set via a Nicholas-type enolate alkylation. Ultimately, undesired C-N cyclization thwarted the final projected C-C bond forming ring closure, and gilbertine could not be prepared by this route.",10.1021/acs.joc.6b00348,2016-05-13,0.6879947194850451
Journal of Organic Chemistry,Rapid and Stereoselective Access to 6″-Amino-6″-deoxy-α-GalCer Scaffolds,"This work describes a highly efficient route to an orthogonally protected α-galactosylphytosphingosine (α-GalPhyt) from which 6″- N -modified α-galactosylceramide (α-GalCer) analogues can be synthesized rapidly and on-scale. Key to this route is the use of a d -galactal-derived 1,2-anhydro donor that undergoes an α-selective glycosylation with a sphingoid acceptor. The resulting α-GalPhyt intermediate can be orthogonally deprotected, enabling selective manipulation at either the C-6″ position of the galactose ring or at C-2 of the sphingoid lipid. The utility of this approach was demonstrated by the synthesis of the potent natural killer (NK) T cell agonist, NU-α-GalCer, and a novel 6″-amino-6″-deoxy analogue of another notable agonist, 7DW8–5, both from the same key intermediate.",10.1021/acs.joc.5c00041,2025-03-04,0.6879790510425274
Angewandte Chemie International Edition,Studies in the Total Synthesis of Heliquinomycinone: Proof of Concept and Assembly of a Fully Mature Spirocyclization Precursor,"A strategy for the synthesis of heliquinomycin, a selective helicase inhibitor, hinges on the spirocyclization of precursor 3. Naphthofuran 1 and aldehyde 2 were readily prepared and used in the synthesis of 3. The key steps in the total synthesis of heliquinomycinone (4) include the regioselective dihydroxylation of 3, and a novel spirocyclization under Mitsunobu conditions.",10.1002/1521-3773(20011217)40:24<4709::aid-anie4709>3.0.co;2-q,2001-12-17,0.6879367017550514
Journal of the American Chemical Society,"An Enantioselective Synthetic Route to Atractyligenin Using the Oxazaborolidine-Catalyzed Reduction of β-Silyl- or β-Stannyl-Substituted α,β-Enones as a Key Step","In this paper, we describe a novel catalytic enantioselective synthetic route to the bicyclic tetraene ester 3, a key intermediate for the synthesis of the naturally occurring adenosine diphosphate transport inhibitor atractyligenin ( 2 ). The success of this route depended on the extension of the oxazaborolidine-catalyzed (CBS) reduction of an achiral β-stannyl-substituted α,β-enone ( 6c ) to form a chiral allylic alcohol and further steps to effect simultaneous transfer of chirality, carbocycle formation, and quaternary stereocenter formation, which led to the triene acid 13 . The conversion of 13 to 3 was carried out efficiently by a four-step sequence involving iodolactonization, double elimination, and esterification. The combined use of the CBS reduction of appropriate α,β-enones and Claisen rearrangement provides an important synthetic avenue to many types of natural products containing quaternary stereocenters embedded in cyclic networks.",10.1021/ja973034o,1997-12-01,0.6879229350289007
Synlett,Asymmetric Organocatalytic Cyclopropanation on Chiral Menthyl Acrylate for the Synthesis of (–)-trans-2-Aminomethylcyclopropanecarboxylic Acid [(–)-TAMP],"An enantioselective synthesis of (–)- trans -2-aminomethylcyclopropanecarboxylic acid [(–)-TAMP], a partial agonist for GABAc receptor, has been achieved as the hydrochloride salt in 3.9% overall yield for total eight steps from l -menthol. The synthesis features double asymmetric cyclopropanation that employs cinchona alkaloid derived organocatalyst and l -menthyl chiral auxiliary.",10.1055/s-0033-1340953,2014-03-14,0.6879001416873084
Organic Process Research & Development,An Alternative Route to the Anticancer Agent: 2-Fluorofucose from Readily Available L-(−)Rhamnose and Mechanistic Insights into a Zinc/Ammonium Iodide-Mediated Elimination Reaction,"2-Fluorofucose ( 6 ) is a fucosylation inhibitor administered orally to patients with advanced solid tumors. 6 exhibits antitumor activity, putatively via multiple mechanisms. Herein, we report a robust formal synthetic route for obtaining 6 ( SGD-2083 ) from L-(−)rhamnose as a starting material. This provides an alternative expedient route toward its commercial-scale production for a First in Human (FIH) campaign. In this work, we have optimized a linear synthesis constituting a sequential, strategic protection, oxidation, reduction, and bromination. Importantly, we biased the reactivity of an organozinc intermediate toward an ionic pathway by inclusion of salt additives. Computational insights and mechanistic studies highlighting the role of relative configuration and the reactivity of these protected sugars are the key toward the success of this efficient and scalable route. The efficiency of this eight-step linear synthesis was demonstrated on multigram scale, furnishing key intermediate 4 in 32% overall yield.",10.1021/acs.oprd.2c00146,2022-08-05,0.6878803569658162
Journal of Organic Chemistry,A Scalable Synthesis of the Difluoromethyl-<i>allo</i>-threonyl Hydroxamate-Based LpxC Inhibitor LPC-058,"The difluoromethyl-allo-threonyl hydroxamate-based compound LPC-058 is a potent inhibitor of UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine deacetylase (LpxC) in Gram-negative bacteria. A scalable synthesis of this compound is described. The key step in the synthetic sequence is a transition metal/base-catalyzed aldol reaction of methyl isocyanoacetate and difluoroacetone, giving rise to 4-(methoxycarbonyl)-5,5-disubstituted 2-oxazoline. A simple NMR-based determination of enantiomeric purity is also described.",10.1021/acs.joc.6b00589,2016-04-29,0.6878754669385946
Tetrahedron,"An efficient synthesis of novel tetrahydrochromeno[2,3-b]chromenes",,10.1016/j.tetlet.2010.05.025,2010-05-13,0.6878517979609524
Tetrahedron,"An efficient synthesis of novel 1,3-oxazolo64,5-d9pyridazinones",,10.1016/s0040-4039(04)00884-6,2004-05-26,0.6878517979609524
Tetrahedron,A novel and efficient synthesis of porphine,,10.1016/j.tetlet.2006.10.010,2006-10-21,0.6878517979609524
Tetrahedron,First efficient synthesis of novel oxophenyl-arcyriaflavin analogs,,10.1016/j.tetlet.2005.07.006,2005-07-23,0.6878517979609524
Tetrahedron,A novel and efficient synthesis of Entecavir,,10.1016/j.tetlet.2012.05.058,2012-05-17,0.6878517979609524
Tetrahedron,"An efficient synthesis of novel 1,3-oxazolo[4,5- d ]pyridazinones",,10.1016/j.tetlet.2004.04.093,2004-05-08,0.6878517979609524
Tetrahedron,An efficient synthesis of novel estrieno[2.3- b ] and [3.4- c ]pyrroles,,10.1016/s0040-4039(03)00541-0,2003-03-25,0.6878517979609524
Tetrahedron,Novel and efficient synthesis of perfluoroalkylated arylphosphines,,10.1016/s0040-4039(00)00445-7,2000-05-01,0.6878517979609524
Tetrahedron,A novel and efficient synthesis of L-vinylglycine,,10.1016/s0040-4039(01)80177-5,1984-01-01,0.6878517979609524
Tetrahedron,A novel and efficient synthesis of isoguanosine,,10.1016/s0040-4039(00)96067-2,1987-01-01,0.6878517979609524
Synlett,Total Synthesis of (-)-Chokol A by an Asymmetric Domino Michael Addition-Dieckmann Cyclization,"A convergent and asymmetric total synthesis of (-)-chokol A was accomplished in six steps starting from the α,β-unsaturated ester (E)-9 in an overall yield of 27% with an enantiomeric excess of 95%. The key step of this synthesis is the asymmetric tandem conjugate addition-Dieckmann cyclization of the higher-order cuprate 8 derived from vinyl bromide 7 with the α,β-unsaturated ester (E)-9.",10.1055/s-2006-949653,2006-09-01,0.6878415289291604
Organic Letters,Asymmetric Formal Synthesis of (−)-Paroxetine,"A concise, asymmetric formal synthesis of (−)-paroxetine is reported. The synthetic strategy features an asymmetric hydrogenation for constructing the chiral center and a phosphate-group-involved intramolecular S N 2 reaction for the construction of the trans -3,4-disubstituted piperidine scaffold. This synthetic route is concise and practical for (−)-paroxetine synthesis.",10.1021/acs.orglett.5c01622,2025-05-19,0.687829036914999
Organic Process Research & Development,The Development of Practical Synthetic Routes to a CB<sub>2</sub> Agonist: Efficient Construction of a Densely Substituted Purine Core,"An efficient and scalable process for the preparation of a purine-based CB 2 agonist was developed. The production route to the requisite purine core relies on N -acylation and sequential substitution of a 5-amino-4,6-dichloropyrimidine with two amine building blocks followed by a cyclocondensation reaction. The chemistry was successfully employed to rapidly prepare over 5 kg of the active pharmaceutical ingredient. To further improve efficiencies, postproduction development resulted in a rearranged synthesis which reduced the need for pressure reactors and introduced the most costly reagent in the final step.",10.1021/op300278c,2013-01-03,0.6878111149525642
Tetrahedron,"The synthesis of (4R-cis)-1,1-dimethylethyl 6-cyanomethyl-2,2-dimethyl-1,3-dioxane-4-acetate, a key intermediate for the preparation of CI-981, a highly potent, tissue selective inhibitor of HMG-CoA reductase",,10.1016/s0040-4039(00)74189-x,1992-04-01,0.6877653117585395
Organic Process Research & Development,The Synthesis of a 5HT<sub>2C</sub> Receptor Agonist,"This report describes the large-scale synthesis of 1 that features a Fischer indole strategy to form an advanced intermediate followed by reduction to the indoline to construct the tetracyclic core of the molecule. Resolution using dibenzoyl- d -tartaric acid affords access to a single enantiomer, from which a Suzuki coupling builds in the biaryl functionality. Deprotection followed by salt formation furnishes the desired target molecule.",10.1021/op700121y,2007-10-18,0.6877583999042217
Tetrahedron,"Synthesis of 8-substituted xanthines via 5,6-diaminouracils: an efficient route to A2A adenosine receptor antagonists",,10.1016/j.tetlet.2008.05.071,2008-05-21,0.6876644975676109
Journal of Organic Chemistry,"Ring-Closing Metathesis of Allylsilanes As a Flexible Strategy toward Cyclic Terpenes. Short Syntheses of Teucladiol, Isoteucladiol, Poitediol, and Dactylol and an Attempted Synthesis of Caryophyllene","The development of a strategy consisting of allylsilane ring-closing metathesis and subsequent S(E)' electrophilic desilylation (allylsilane RCM/S(E)') to construct exo-methylidenecycloalkanes is described. Its utility is documented in short syntheses of teucladiol and poitediol. A key transformation in the synthesis of teucladiol is an aldol addition that establishes three stereochemical relationships in one step with ≥10:1 diastereoselectivity and provides a fascinating example of double stereodifferentiation/kinetic resolution with racemic reaction partners in the context of natural product synthesis. The synthesis of (±)-teucladiol required five steps from cyclopentenone and proceeded in 28% overall yield; adaptation of this route to an enantioselective synthesis of (-)-teucladiol enabled the determination of the absolute configuration of this terpene natural product. The use of fluoride-mediated conditions in the final desilylation step preserves the location of the alkene, delivering the natural product (±)-isoteucladiol (five steps and 21% yield from cyclopentenone). The synthesis of poitediol showcases the power of RCM for constructing eight-membered rings and features a highly diastereoselective epoxidation/fluoride-mediated fragmentation sequence for installing the exo-methylidene group with an adjacent hydroxyl-bearing stereocenter. The synthesis of (±)-poitediol required seven steps and proceeded in 18% overall yield. Again, fluoride-mediated desilylation of a late-stage intermediate (with retention of double-bond location) delivered the natural product (±)-dactylol (seven steps and 24% yield). Efforts directed toward incorporating the RCM/S(E)' sequence into a synthesis of caryophyllene are also disclosed. While ultimately unsuccessful, these efforts resulted in the identification of a novel metal alkylidene-promoted deallylation reaction of terminal 1,4-dienes. A possible mechanism for this unexpected deallylation reaction of 1,4-dienes is provided.",10.1021/jo101439h,2010-09-13,0.6875855479762969
Angewandte Chemie International Edition,Total Synthesis of Chloptosin,Two is better that one: A new organocatalytic route for the asymmetric preparation of the embedded piperazic acids and a Stille coupling of an ortho-chloropyrroloindole served as key steps in the total synthesis of the dimeric cyclopeptide chloptosin (see structure).,10.1002/anie.201002880,2010-07-19,0.6875677624992023
Organic Process Research & Development,"Expedient Synthesis of MLN1251, A CCR5 Antagonist for Treatment of HIV",An expedient synthesis of MLN1251 has been developed that allows for the production of multikilogram quantities of the target compound. The key transformation is synthesis of a 5-hydroxyindole by a Nenitzescu reaction. The longest linear sequence is five steps with an overall yield of approximately 31%.,10.1021/op060245h,2007-01-18,0.6874612870280598
Organic Process Research & Development,"Development of a Synthetic Process for K-8986, an H1-Receptor Antagonist","This article describes the development of a robust and scalable synthetic process for K-8986 ( 1 ). To solve the problems in terms of the physicochemical properties of 6 (a free base unit of 1 ), we have screened the suitable salt forms of the target. The monomaleate salt was the most suitable form for the API. To overcome challenges regarding the unremovable impurity Imp B caused by the carryover of piperazine in the medicinal chemistry route, we designed and developed a novel synthetic route. This route furnished more opportunities to purify the synthetic intermediates after introduction of the piperazine unit. Both impurities and co-products in each step of the revised synthesis could be easily removed via filtration, leveraging the low solubility of benzothiazine derivatives. The newly established process was applied to the synthesis of 1 (the monomaleate salt of 6 ) on a practical scale, achieving high purity and reproducibility.",10.1021/acs.oprd.8b00380,2019-01-10,0.6874106942097279
Journal of Organic Chemistry,Efficient Total Synthesis of Sapinofuranone B,"[structure: see text] An efficient enantioselective synthesis of sapinofuranone B (1) using Sharpless asymmetric dihydroxylation, Sonogashira coupling, and Wittig olefination as the key steps is described.",10.1021/jo048087k,2005-02-26,0.6872652844152628
Organic Process Research & Development,Development of a First-Generation Stereocontrolled Manufacturing Process of TRPA1 Inhibitor GDC-6599,"We report a fit-for-purpose, stereocontrolled, and chromatography-free first-generation manufacturing process for GDC-6599 ( 1 ), a TRPA1 inhibitor, to enable first-in-human clinical trials. Key steps in the process include consecutive KRED-mediated asymmetric ketone reductions, nucleophilic cyanation, 1,2,4-oxadiazole formation, and late stage purinone N -alkylation. The 13-step process successfully produced 4.39 kg of GDC-6599 ( 1 ) in 11% overall yield with 99.6 A% HPLC purity, >99.9:0.1 er, and >99.9:0.1 dr.",10.1021/acs.oprd.4c00134,2024-05-24,0.6872389215115402
Organic Letters,Total Synthesis of Clavilactone B: A Radical Cyclization–Fragmentation Strategy,"A new synthetic route to clavilactone B, a naturally occurring inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, is disclosed. The route features a sequential samarium-mediated radical cyclization-fragmentation of an indanone derivative, which provides rapid access to a 10-membered carbocyclic motif fused to an aromatic ring.",10.1021/ol503356m,2014-12-16,0.6872336070301431
Synthesis,Total Synthesis of 6-Epi-Erythronolide Derivatives,"All articles of this category A concise convergent synthesis of 6-epi-erythronolide B 3,5-acetonide and of (9 R )-dihydro-6-epi-erythronolide B from ( R )-2, 3- O -isopropylideneglyceraldehyde is described. The key step in the synthesis involves the coupling of two aldehydes, comprising the C1-C6 and the C9-C13 portions of the target molecule, across a formal acetylide dianion (C7-C8 (Scheme 1).",10.1055/s-1992-34154,1992-01-01,0.6872150464470763
Organic Letters,Asymmetric Total Synthesis of Neobraclactone C,"Asymmetric total synthesis of neobraclactone C was finished for the first time using the convergent synthetic strategy in 22 steps in the longest linear sequence from known materials. The key steps include a steric hindrance/hydrogen bond dual-controlled Heck arylation of α,β-unsaturated ketone to construct hemiketal and cis -alkenyl in one step and a CeCl 3 -catalyzed tricycle formation.",10.1021/acs.orglett.2c03970,2022-12-15,0.6871093087460156
Tetrahedron,A convergent rgiospecific route to the aklavinone ring system,,10.1016/s0040-4039(01)82008-6,1981-01-01,0.6870000823345163
Tetrahedron,Synthesis of heterosteroids. First synthesis of oxa steroid from cholic acid,,10.1016/j.tetlet.2009.10.141,2009-11-12,0.6869875780208741
Organic Process Research & Development,"Synthesis of 2,3,4,5-Tetrahydrobenzo[1,4]thiazepines via <i>N</i>-Acyliminium Cyclization","We report an efficient and scalable synthesis of 7-methoxy-2,3,4,5-tetrahydrobenzo[1,4]thiazepine, the core structure of biologically active molecules like JTV-519 and S107. This synthetic route, starting with 4-methoxythiophenol and proceeding via acyliminum cyclization, gives the target product in four steps and 68% overall yield and is a substantial improvement over previously published processes. Nine additional examples of tetrahydrobenzo[1,4]thiazepine synthesis via acyliminium ring closure are also presented.",10.1021/acs.oprd.7b00260,2017-09-28,0.686953624706176
Organic Letters,Asymmetric Total Synthesis of Laurallene,The asymmetric total synthesis of laurallene was achieved in 13 steps for the longest linear sequence with 3.3% overall yield from commercially available trans-2-pentenal. This synthesis features the highly efficient construction of a branched ether system with five oxygenated asymmetric stereocenters by the combination of a palladium-catalyzed alkoxy substitution reaction and a cobalt-catalyzed Mukaiyama oxidative cyclization.,10.1021/acs.orglett.8b03889,2019-01-08,0.6869425770293851
Organic Process Research & Development,"Development of a Practical Synthesis of a Peripherally Selective Noradrenaline Reuptake Inhibitor Possessing a Chiral 6,7-<i>trans</i>-Disubstituted-1,4-oxazepane as a Scaffold","A practical synthesis of a peripherally selective noradrenaline reuptake inhibitor that has a chiral 6,7- trans -disubstituted-1,4-oxazepane as a new class of scaffold is described. The amino alcohol possessing the desired stereochemistry was obtained with excellent dr and ee, starting from a commercially available aldehyde via a Morita–Baylis–Hillman reaction, Michael addition, isolation as maleic acid salt, reduction, and diastereomeric salt formation with (+)-10-camphorsulfonic acid. The desired single stereoisomer obtained at an early stage of the synthesis was used for seven-membered ring formation in fully telescoped processes, providing the chiral 6,7- trans -disubstituted-1,4-oxazepane efficiently. In addition to controls of dr and ee of the chiral 1,4-oxazepane, and control of N, O -selectivity in S N 2 reaction of the intermediate mesylate with a pyridone derivative, finding appropriate intermediates that were amenable to isolation and upgrade of purity enabled a practical chiral HPLC separation-free, column chromatograph-free synthesis of the drug candidate with excellent chemical and optical purities in a higher overall yield.",10.1021/acs.oprd.7b00313,2017-11-01,0.6868564878590783
Journal of the American Chemical Society,Enantioselective Synthesis of Hemiaminals via Pd-Catalyzed C–N Coupling with Chiral Bisphosphine Mono-oxides,"A novel approach to hemiaminal synthesis via palladium-catalyzed C-N coupling with chiral bisphosphine mono-oxides is described. This efficient new method exhibits a broad scope, provides a highly efficient synthesis of HCV drug candidate elbasvir, and has been applied to the synthesis of chiral N,N-acetals.",10.1021/jacs.5b05934,2015-09-28,0.686823686699331
Tetrahedron,"A convergent synthesis of Ro24-5913, a novel leukotriene D4 antagonist",,10.1016/0040-4039(96)01190-2,1996-07-01,0.6867588796729505
Journal of Organic Chemistry,"Synthesis of the 6-Azaindole Containing HIV-1 Attachment Inhibitor Pro-Drug, BMS-663068","The development of a short and efficient synthesis of a complex 6-azaindole, BMS-663068, is described. Construction of the 6-azaindole core is quickly accomplished starting from a simple pyrrole, via a regioselective Friedel-Crafts acylation, Pictet-Spengler cyclization, and a radical-mediated aromatization. The synthesis leverages an unusual heterocyclic N-oxide α-bromination to functionalize a critical C-H bond, enabling a highly regioselective copper-mediated Ullmann-Goldberg-Buchwald coupling to install a challenging triazole substituent. This strategy resulted in an efficient 11 step linear synthesis of this complex clinical candidate.",10.1021/jo5016008,2014-08-21,0.686755884209832
Organic Process Research & Development,Scale-Up Synthesis of Antidepressant Drug Vilazodone,"A scale-up synthesis of antidepressant drug vilazodone was accomplished in five steps. Friedel–Crafts acylation of 1-tosyl-1 H -indole-5-carbonitrile with 4-chlorobutyryl chloride, selective deoxygenation in NaBH 4 /CF 3 COOH system coupled with ethyl 5-(piperazin-1-yl)-benzofuran-2-carboxylate hydrochloride, one-step deprotection and esterolysis, and the final ammonolysis led to the target molecule vilazodone in 52.4% overall yield and 99.7% purity. This convenient and economical procedure is remarkably applicable for scale-up production.",10.1021/op300171m,2012-08-29,0.6867178036568056
Organic Letters,An Isofagomine Analogue with an Amidine at the Pseudoanomeric Position,"(3R,4R,5R)-2-Imino-3,4-dihydroxy-5-hydroxymethylpiperidine hydrocloride or isofagomidine was synthesized from D-arabinose in 12 steps and an overall yield of 9.9%. The synthesis proceeded by introduction of an aminomethyl group in the 4-position of D-arabinose and conversion of C-1 into a nitrile. The key step in the synthesis was a copper-catalyzed cyclization of aminonitrile to amidine. Isofagomidine was a potent α-mannosidase inhibitor (K(i) = 0.75 μM).",10.1021/ol200942g,2011-05-06,0.6867081018510716
Journal of Organic Chemistry,Enantioselective Total Synthesis of Desbromoarborescidines A–C and the Formal Synthesis of (<i>S</i>)-Deplancheine,"Starting from Boc-protected tryptamine and (S)-tetrahydro-5-oxo-2-furancarboxylic acid, facile enantioselective total synthesis of desbromoarborescidines A-C and the formal synthesis of (S)-deplancheine have been accomplished via a common intermediate (S)-indolo[2,3-a]quinolizine. Synthesis of enantiomerically pure (S)-acetoxyglutarimide, stereoselective reductive intramolecular cyclization, hydroxyl group-assisted in situ N-Boc-deprotection, selective deoxygenation of the xanthate ester, and lactam hydrolysis followed by an appropriate exchange of nitrogen regioselectivity in intramolecular cyclization were the decisive steps.",10.1021/jo401079v,2013-06-12,0.6866977982796674
Journal of Organic Chemistry,Sulfoxide-Mediated Asymmetric Synthesis of Glycosidase Inhibitor Precursors,"The highly diastereoselective DIBALH and DIBALH/ZnBr(2) reduction of enantiomerically pure (5S,(S)S)-3-ethoxy-5-(p-tolylsulfinyl)cyclopentenone (9) is used as a key step to the synthesis of oxazolidinone 2, a precursor of glycosidase inhibitor mannostatin. Compound 9 was obtained from 3-ethoxycyclopentenone by direct sulfinylation with (S)-N-benzyl-N-(p-tolylsulfinyl)propionamide.",10.1021/jo961774u,1997-04-01,0.6866791877096465
Journal of Organic Chemistry,"A Stereoselective Synthesis of BMS-262084, an Azetidinone-Based Tryptase Inhibitor",A highly stereoselective synthesis of the novel tryptase inhibitor BMS-262084 was developed. Key to this synthesis was the discovery and development of a highly diastereoselective demethoxycarbonylation of diester 12 to form the trans-azetidinone 13. BMS-262084 was prepared in 10 steps from D-ornithine in 30% overall yield.,10.1021/jo010757o,2002-04-27,0.6866338115442989
Organic Process Research & Development,"Development of a Manufacturing Route toward AMG 193, an MTA-Cooperative PRMT5 Inhibitor","AMG 193 is an MTA-cooperative PRMT5 inhibitor that has shown promising antitumor activity in the clinic. Despite a five-month development window from molecule identification to multi-kg manufacture of this small molecule drug substance, a robust process was developed, featuring multiple bio- and chemocatalytic steps. In particular, two wild-type enzymes were applied to the synthesis of key building blocks, including the formation of a chiral morpholine fragment, which was further improved through directed evolution. Additionally, a selective Ir-catalyzed C–H borylation, followed by a Pd-catalyzed Suzuki coupling and cyclization, was executed in a single pot, enabling rapid access to the naphthyridine core. Altogether, the development of this convergent synthesis has enabled a continued supply of AMG 193 for clinical studies.",10.1021/acs.oprd.5c00310,2025-10-18,0.6866202638720353
Synthesis,New Efficient Synthesis of Combretastatin A-4 via Colvin Rearrangement,A new four-step approach for the synthesis of anticancer agent combretastatin A-4 (CA-4) has been developed. The method includes the Colvin rearrangement of the benzophenone derivative phenstatin to the key diarylalkyne followed by stereoselective semi-reduction to CA-4 in good overall yield.,10.1055/s-0030-1260248,2011-09-29,0.6866053792931569
Synlett,A Short and Efficient Synthesis of (-)-Diospongin A,The synthesis of (-)-diospongin A has been achieved from benzaldehyde in six steps with an overall yield of 29%.,10.1055/s-2006-956485,2006-12-01,0.6866031254852295
Journal of Organic Chemistry,A Short and Scalable Route to Orthogonally <i>O</i>-Protected 2-Deoxystreptamine,"A seven-step synthesis of orthogonally O-protected 2-deoxy-streptamine has been developed from readily available neomycin, with an overall yield of 28%. Key chemical transformations include a chemoselective glycosidic bond hydrolysis and two regioselective protective group manipulations involving acetylation and deacetylation. The synthetic route is amenable to scale-up for the production of multigram quantities of enantiopure and orthogonally O-protected 2-deoxystreptamine, a versatile scaffold for the generation of libraries of RNA-targeting ligands.",10.1021/jo062369y,2007-03-27,0.6864300544787344
Synlett,Total Synthesis of Acetylcholinesterase Inhibitor Macakurzin C,"A concise total synthesis of macakurzin C has been accomplished in nine steps (21% overall yield) from commercially available phloroglucinol, featuring a sequential aromatic Claisen rearrangement–cyclization.",10.1055/s-0034-1378904,2014-10-29,0.6864084407574512
Tetrahedron,A novel approach to a key intermediate in the total synthesis of α-onocerin,,10.1016/s0040-4039(01)99201-9,1961-01-01,0.6863931710698017
Journal of the American Chemical Society,Convergent and Efficient Total Synthesis of (+)-Heilonine Enabled by C–H Functionalizations,"High Resolution Image Download MS PowerPoint Slide We report a convergent and efficient total synthesis of the C- nor D- homo steroidal alkaloid (+)-heilonine with a hexacyclic ring system, nine stereocenters, and a trans -hydrindane moiety. Our synthesis features four selective C–H functionalizations to form key C–C bonds and stereocenters, a Stille carbonylative cross-coupling to connect the AB ring system with the DEF ring system, and a Nazarov cyclization to construct the five-membered C ring. These enabling transformations significantly reduced functional group manipulations and delivered (+)-heilonine in 11 or 13 longest linear sequence (LLS) steps.",10.1021/jacs.3c13492,2024-01-16,0.6863699370601802
Organic Process Research & Development,"A Practical, Protecting-Group-Free Synthesis of a PI3K/mTOR Inhibitor",We report a practical and protecting-group-free synthesis amenable to produce multikilogram amounts of PI3K/mTOR inhibitor GDC-0980 . The route employed metalation/formylation and reductive amination followed by a metal catalyzed Suzuki–Miyaura cross-coupling. The metalation was performed via triarylmagnesiate intermediates allowing formylation under noncryogenic conditions. 2-Picoline·BH 3 was employed to replace Na(OAc) 3 BH in the reductive amination and to eliminate the use of molecular sieves. A concise one-step synthesis was developed for the selective monoamidation of piperazine with ( S )-lactate to produce the piperazine lactamide starting material. The boronic acid was produced from 2-amino-5-bromopyrimidine in a one-step and protecting-group-free approach. The final crystallization in 1-propanol and water afforded the API in 59% overall yield in four steps and >99% purity by HPLC.,10.1021/op500366s,2015-02-13,0.6863458403510527
Synthesis,"Synthesis and Resolution of a Chiral Diamine: 2,2′-(Propane-2,2-diyl)dipyrrolidine","A short and practical synthesis of a new chiral dipyrrolidine is presented. The three-step route includes a hydrogenation and a resolution with mandelic acid, which easily affords large quantities of the title compound.",10.1055/s-0036-1589023,2017-05-18,0.6862678661050061
Organic Letters,"Enantioselective, Organocatalytic Strategy for the Oxazolomycin Core: Formal Synthesis of (+)-Neooxazolomycin","A concise, organocatalytic, enantioselective route to the γ-lactam core of the oxazolomycins was developed. Key steps include a Lewis base-catalyzed, Michael proton transfer-lactamization organocascade, a one-pot N-methylation and diastereoselective α-alkylation, a diastereotopic group-selective reduction, a substrate-directed allylic hydroxylation, and a lanthanide-mediated organolithium addition to append the side chain. A formal synthesis of (+)-neooxazolomycin via interception of a Kende intermediate, accessed in 10 steps (previously 24 steps from α-d-glucose), enabled confirmation of the relative and absolute stereochemistry.",10.1021/acs.orglett.0c03511,2020-11-23,0.6862633591249028
Tetrahedron,"Studies toward the total synthesis of Sch 202596, an antagonist of the galanin receptor subtype GalR1: synthesis of geodin, the spirocoumaranone subunit of Sch 202596",,10.1016/s0040-4039(99)02005-5,2000-01-01,0.686251497076142
Journal of Organic Chemistry,Concise Total Syntheses of Variolin B and Deoxyvariolin B,"The total synthesis of the marine alkaloid variolin B has been achieved in 8 steps and 17% overall yield, starting from commercially available 4-chloro-2-methylthiopyrimidine. The key reaction involves the tandem deoxygenation and cyclization of a triarylmethanol using a combination of triethylsilane and trifluoroacetic acid. In addition, the deoxygenated analogue was prepared in 6 steps and 23% overall yield, starting from the same starting material.",10.1021/jo050523v,2005-07-15,0.686236187283674
Organic Process Research & Development,"First Scale-Up Synthesis of FU-23, a Novel Water-Soluble Pleuromutilin-Derived Antibiotic","A first scale-up synthesis of FU-23 ( 1 ), a potent and effective water-soluble pleuromutilin-derived antibiotic, is described. The original synthesis from the medicinal chemistry group provided 1 in seven steps and 10.9% overall yield, required four chromatographies and employed expensive reagents such as AgOCN and 4-acetylsalicoyl chloride. The optimized synthetic route for the preparation of phosphate salt 1 consists of seven linear steps with a 42.8% overall yield. Significant cost reduction and more robust reaction conditions have been developed with no chromatography required at any stage.",10.1021/op100063h,2010-05-12,0.6862201018341171
Tetrahedron,An efficient new approach to the synthesis of the prostaglandins. Synthesis of PGE1,,10.1016/s0040-4039(01)85239-4,1972-01-01,0.686207151527065
Journal of the American Chemical Society,Total Synthesis of (+)-α-Onocerin in Four Steps via Four-Component Coupling and Tetracyclization Steps,"A remarkably short (four steps, 31% overall yield) enantioselective synthesis of the structurally unique C2-symmetric tetracyclic triterpene (+)-alpha-onocerin (1) has been developed. The brevity of this mechanism depends on the assembly of four fragments (two molecules of a chiral epoxy ketone and two molecules of vinyllithium) to generate the chiral bis-epoxide 4 in one step, and on the efficient formation of all four carbocyclic rings in one step by cation-olefin tetracyclization. New and general methodology for the conversion of vinyl tert-butyldimethylsilyl ethers to vinyl triflates with retention of E or Z olefinic geometry also was utilized in the synthesis of 1. A short enantioselective synthesis of a non-C2-symmetric diastereomer of 1 is also described which uses the new methodology.",10.1021/ja027373f,2002-08-31,0.6861841361378621
Synlett,Palladium-Catalyzed Approach to Malasseziazole A and First Total Synthesis of Malasseziazole C,"We describe a convergent route to 5,11-dihydroindolo[3,2- b ]carbazoles using a twofold oxidative cyclization as key step. The method has been applied to the synthesis of a precursor for malasseziazole A and to the first total synthesis of malasseziazole C.",10.1055/s-0034-1380713,2015-04-30,0.686174835607317
Journal of Organic Chemistry,Enantiospecific Synthesis of Optically Active 6-Methoxytryptophan Derivatives and Total Synthesis of Tryprostatin A<sup>1</sup>,"A concise preparation of optically active l or d -6-methoxytryptophan ethyl ester 21 was developed via the Fischer indole/Schöllkopf protocol from 6-methoxy-3-methylindole 16 (four steps, 58% overall yield). This method was extended to the enantiospecific total synthesis of tryprostatin A ( 11 ) via a regiospecific bromination process as a key step. In addition, 6-methoxy-2-bromotryptophan ethyl ester ( 32 ), a potential intermediate for indole alkaloid synthesis, was prepared via this strategy.",10.1021/jo971640w,1997-12-01,0.6861742213895334
Journal of Organic Chemistry,Chemoenzymatic Synthesis of a Chiral Ozanimod Key Intermediate Starting from Naphthalene as Cheap Petrochemical Feedstock,"Ozanimod represents a recently developed, promising active pharmaceutical ingredient (API) molecule in combating multiple sclerosis. Addressing the goal of a scalable, economically attractive, and technically feasible process for the manufacture of this drug, a novel alternative synthetic approach toward ( S)-4-cyano-1-aminoindane as a chiral key intermediate for ozanimod has been developed. The total synthesis of this intermediate is based on the utilization of naphthalene as a readily accessible, economically attractive, and thus favorable petrochemical starting material. At first, naphthalene is transformed into 4-carboxy-indanone within a four-step process by means of an initial Birch reduction, followed by an isomerization of the C═C double bond, oxidative C═C cleavage, and intramolecular Friedel-Crafts acylation. The transformation of the 4-carboxy-indanone into ( S)-4-cyano-1-aminoindane then represents the key step for introducing the chirality and the desired absolute S configuration. When evaluating complementary biocatalytic approaches based on the use of a lipase and transaminase, respectively, the combination of a chemical reductive amination of the 4-carboxyindanone followed by a subsequent lipase-catalyzed resolution turned out to be the most efficient route, leading to the desired key intermediate ( S)-4-cyano-1-aminoindane in satisfactory yield and with excellent enantiomeric excess of 99%.",10.1021/acs.joc.8b03290,2019-04-12,0.6860895271768571
Organic Process Research & Development,Toward the Development of a Manufacturing Process for the Insecticide Tyclopyrazoflor. Part I. Evaluation of Strategies using Ullmann Coupling of Pyrazole Derivatives,"Synthetic strategies based on Ullmann coupling of functionalized pyrazoles and 3-halopyridine to access the insecticide tyclopyrazoflor ( 1 ) were evaluated. A five-step route featuring a middle-stage Ullmann coupling approach was selected as the lead route for optimization and was scaled up in a pilot plant at more than 50 kg scale of each step. This route started from reductive chlorination of 4-nitropyrazole followed by acetylation to provide N -(3-chloro-1 H -pyrazol-4-yl)acetamide as the key coupling nucleophile, which readily coupled with 3-bromopyridine in the presence of copper(I) chloride as catalyst and 1,2-dimethylethylenediamine (DMEDA) as ligand. Subsequent NaBH 4 reduction afforded the corresponding ethyl amine, which was coupled with 3-((3,3,3-trifluoropropyl)thio)propanoyl chloride to furnish tyclopyrazoflor ( 1 ). This highly concise route offered a critical foundation for development of a scalable manufacturing process.",10.1021/acs.oprd.2c00296,2022-11-20,0.6860654365947644
Journal of Organic Chemistry,"Improved Synthesis of 3-Substituted-4-amino-[3,2-<i>c</i>]-thienopyridines","Two syntheses of 3-substituted-4-amino-[3,2-c]thienopyridines have been developed to replace the standard literature route to these compounds, which uses unattractive conditions involving azide and high temperatures. The first synthesis utilizes a Friedel-Crafts reaction as its key ring-forming step, whereas the second route relies on an unprecedented intramolecular reductive cyclization between a nitroolefin and a nitrile as its key ring-forming step. The development and optimization of each 3-substituted-4-amino-[3,2-c]thienopyridine synthesis is discussed and a comparison of the routes is presented.",10.1021/jo9003772,2009-04-16,0.6860504548648216
Tetrahedron,"Novel asymmetric dealkoxycarbonylation of 3-oxo-8-azabicyclo[3.2.1]-octane-2,4-dicar☐ylates using porcine liver esterase: A new route to (−)-anhydroecgonine methyl ester",,10.1016/s0040-4039(99)00976-4,1999-07-01,0.6860096101042269
Tetrahedron,"Stereoselective total synthesis of (−)-zeylenol, a key intermediate for the synthesis of (+)-pipoxide, (−)-uvarigranol G and (−)-tonkinenin A",,10.1016/j.tetlet.2017.02.003,2017-02-04,0.6859544413652546
Tetrahedron,A new synthetic route to functionally substituted cyclopentenones,,10.1016/s0040-4039(01)92127-6,1974-01-01,0.6859450653648768
Journal of the American Chemical Society,Total Synthesis of Gelsenicine via a Catalyzed Cycloisomerization Strategy,"The first total synthesis of (±)-gelsenicine is reported. The synthetic route is highly efficient (13 steps), featuring (1) a pivotal metal-catalyzed isomerization/rearrangement process that forges the central core of the molecule and (2) two facile C-N bond-forming steps that establish the flanking heterocycles.",10.1021/jacs.5b12263,2015-12-30,0.685932422020931
Journal of Organic Chemistry,A Concise Synthesis of (<i>S</i>)-<i>N</i>-Ethoxycarbonyl-α-methylvaline,A practical and efficient protocol for the three-step synthesis of (S)-N-ethoxycarbonyl-alpha-methylvaline 3 is described which utilizes readily available commercial starting materials. The key transformations involve resolution-crystallization of tartrate salt 6 followed by a one-pot procedure for the preparation of 3 which is isolated as the dicyclohexylamine salt in 45% overall yield and in 91-95% ee.,10.1021/jo7012862,2007-08-22,0.685892291480804
Journal of Organic Chemistry,Total Synthesis of Berkeleylactone A,"The first total synthesis of the potent antibiotic berkeleylactone A is described in 10 steps with an overall yield of 9.5%. A key step of our concise route is a late-stage, highly diastereoselective, sulfa-Michael addition. The 16-membered macrocyclic lactone was formed via ring closing metathesis and subsequent chemoselective reduction. The absolute stereochemical configuration was confirmed by single-crystal X-ray analysis. Synthetic berkeleylactone A was tested against several methicillin-resistant Staphylococcus aureus strains, and its potent antibacterial activity was verified.",10.1021/acs.joc.9b00850,2019-05-13,0.6858320785868278
Synthesis,An Asymmetric Synthesis of (+)-Erysotramidine,"A new asymmetric total synthesis of the erythrinan alkaloid erysotramidine is described, which uses chiral base desymmetrisation, N-acyliminium addition, and 6-exo-trig radical cyclisation as the key steps.",10.1055/s-2005-918478,2005-01-01,0.6857990532449707
Angewandte Chemie International Edition,Concise and Practical Asymmetric Synthesis of a Challenging Atropisomeric HIV Integrase Inhibitor,"A practical and efficient synthesis of a complex chiral atropisomeric HIV integrase inhibitor has been accomplished. The combination of a copper-catalyzed acylation along with the implementation of the BI-DIME ligands for a ligand-controlled Suzuki cross-coupling and an unprecedented bis(trifluoromethane)sulfonamide-catalyzed tert-butylation renders the synthesis of this complex molecule robust, safe, and economical. Furthermore, the overall synthesis was conducted in an asymmetric and diastereoselective fashion with respect to the imbedded atropisomer.",10.1002/anie.201501575,2015-05-04,0.6857459751569296
Journal of Organic Chemistry,A Novel One-Step Diastereo- and Enantioselective Formation of <i>trans</i>-Azetidinones and Its Application to the Total Synthesis of Cholesterol Absorption Inhibitors,An efficient and practical asymmetric process was developed for the synthesis of azetidinone-based cholesterol absorption inhibitors. Key to this synthesis was the discovery of a novel one-step diastereo- and enantioselective formation of trans beta-lactams starting from commercially available 3(S)-hydroxy-gamma-lactone. Various trans beta-lactams can be prepared in good yields and with better than 95:5 enantio- and diastereoselctivity. A Lewis acid-catalyzed aldol condensation and a highly enantioselective oxazaborolidine-catalyzed chiral reduction completes the side chain.,10.1021/jo990428k,1999-04-21,0.685721168097488
Journal of Organic Chemistry,Gram Scale Synthesis of the Glucuronide Metabolite of ABT-724,"A gram scale synthesis of the glucuronide metabolite of ABT-724 is reported. Glycosidic coupling between a trichloroacetimidate glucuronyl donor and a Cbz-protected hydroxypyridylpiperazine glycosyl acceptor is the key step in the synthesis, since attempts to directly glucuronidate the aglycon, aglycon derivatives, and other truncated glycosyl acceptors were unsuccessful. The route was used to produce 2.1 g of metabolite in eight steps from 2-chloro-5-hydroxypyridine in 21% overall yield.",10.1021/jo0611972,2006-09-23,0.6856263567109679
Synthesis,"Efficient Asymmetric Synthesis of β-Amino Acid BAY 10-8888/PLD-118, a Novel Antifungal for the Treatment of Yeast Infections","The β-amino acid BAY 10-8888/PLD-118 is currently being investigated in phase II clinical studies as a novel antifungal for the treatment of yeast infections. An efficient asymmetric synthesis of this compound is described. The key step employed a highly enantioselective, quinine-mediated alcoholysis of a meso-anhydride intermediate.",10.1055/s-2003-36265,2003-01-01,0.6856198571877903
Journal of Organic Chemistry,Bone Collagen Cross-Links:  A Convergent Synthesis of (+)-Deoxypyrrololine,"A convergent total synthesis of (+)-deoxypyrrololine (Dpl, 4), a putative cross-link of bone collagen, is described starting from a commercially available L-glutamic acid derivative, (4S)-5-(tert-butoxy)-4-[(tert-butoxycarbonyl)amino]-5- oxopentanoic acid (16). Condensation of aldehyde (S)-(-)-17 with nitro compound (S)-(-)-27, both of which were prepared from a common precursor (S)-16, gave the alpha-hydroxynitro compound 28, which upon acetylation afforded alpha-acetoxynitro compound 14 in good yield. Subsequent condensation and cyclization of alpha-acetoxynitro compound 14 with benzyl isocyanoacetate (15) in the presence of DBU in THF gave the key pyrrole intermediate (S,S)-(-)-12 in 57% yield. N-Alkylation of pyrrole (S,S)-(-)-12 with iodide (S)-(-)-13 using t-BuOK in THF afforded the 2-benzyloxycarbonyl-1,3,4-substituted pyrrole derivative (-)-29 in 42% yield. Removal of the protective groups in (-)-29 followed by hydrogenolysis and decarboxylation afforded the cross-link (+)-Dpl (4) in good overall yield. The synthesis of an analogue (S)-(+)-24 and formation of a novel tetrahydroindole derivative (-)-31 are also described.",10.1021/jo0008901,2000-10-04,0.6856132794099714
Organic Letters,Enantioselective Total Synthesis of Cannabinoids—A Route for Analogue Development,A practical synthetic approach to Δ 9 -tetrahydrocannabinol ( 1 ) and cannabidiol ( 2 ) that provides scalable access to these natural products and should enable the generation of novel synthetic analogues is reported.,10.1021/acs.orglett.7b03668,2018-01-02,0.6856105333831308
Tetrahedron,Catalytic enantioselective synthesis of a key intermediate for the synthesis of prostanoids,,10.1016/0040-4039(91)80522-8,1991-12-01,0.6855941137942724
Tetrahedron,Toxadocial A: A novel thrombin inhibitor from the marine sponge Toxadocia cylindrica,,10.1016/s0040-4039(00)60332-5,1993-02-01,0.6854457665675502
Tetrahedron,"Maedamide, a novel chymotrypsin inhibitor from a marine cyanobacterial assemblage of Lyngbya sp.",,10.1016/j.tetlet.2014.05.099,2014-06-02,0.6854457665675502
Tetrahedron,"Diaporthichalasin, a novel CYP3A4 inhibitor from an endophytic Diaporthe sp.",,10.1016/j.tetlet.2006.11.102,2006-12-13,0.6854457665675502
Tetrahedron,"Tetrapetalone A, a novel lipoxygenase inhibitor from Streptomyces sp.",,10.1016/s0040-4039(03)00007-8,2003-02-01,0.6854457665675502
Journal of Organic Chemistry,Total Synthesis of Sekothrixide Strategically Utilizing Regioselective Coupling of TMS-Protected Epoxy <i>sec</i>-Alcohol with Gilman Reagent,A new efficient synthesis of sekothrixide was established on the basis of our developed regioselective coupling of epoxy sec-alcohol with Gilman reagent guided by a TMS group. The new synthetic route allowed an overall yield of 6.3% (26 steps) from optically active 3-silyloxy-2-methylaldehyde.,10.1021/acs.joc.8b03006,2019-01-04,0.6854168915885224
Organic Letters,"Enantioselective Synthesis of A Key A-Ring Intermediate for the Preparation of 1α,25-Dihydroxyvitamin D<sub>3</sub>","A novel approach to the key A-ring α, β-unsaturated aldehyde 1, an important intermediate for the preparation of 1α,25-dihydroxyvitamin D(3), has been developed. The strategy started from the inexpensive starting material (R)-carvone with an ene reaction serving as the key step toward the potential synthesis of vitamin D(3) analogues bearing the modification at the C-2 position.",10.1021/ol102586w,2010-12-06,0.6853895567217805
Tetrahedron,Cobalt-catalyzed alkyne–dihalomethane–amine coupling: an efficient route for propargylamines,,10.1016/j.tetlet.2012.08.136,2012-09-12,0.6853775986967157
Journal of Organic Chemistry,The Intramolecular Asymmetric Pauson−Khand Cyclization as a Novel and General Stereoselective Route to Benzindene Prostacyclins:  Synthesis of UT-15 (Treprostinil),"A general and novel solution to the synthesis of biologically important stable analogues of prostacyclin PGI(2), namely benzindene prostacyclins, has been achieved via the stereoselective intramolecular Pauson-Khand cyclization (PKC). This work illustrates for the first time the synthetic utility and reliability of the asymmetric PKC route for synthesis and subsequent manufacture of a complex drug substance on a multikilogram scale. The synthetic route surmounts issues of individual step stereoselectivity and scalability. The key step in the synthesis involves efficient stereoselection effected in the PKC of a benzoenyne under the agency of the benzylic OTBDMS group, which serves as a temporary stereodirecting group that is conveniently removed via benzylic hydrogenolysis concomitantly with the catalytic hydrogenation of the enone PKC product. Thus the benzylic chiral center dictates the subsequent stereochemistry of the stereogenic centers at three carbon atoms (C(3a), C(9a), and C(1)).",10.1021/jo0347720,2004-02-19,0.6853158606001619
Journal of the American Chemical Society,Total Synthesis of (−)-Gambierol,"The first total synthesis of (-)-gambierol (1), a marine polycyclic ether toxin, has been achieved. Key features of the successful synthesis include (1) a convergent union of the ABC and EFGH ring fragments (5 and 6, respectively) via our developed B-alkyl Suzuki-Miyaura cross-coupling strategy leading to the octacyclic polyether core 4 and (2) a late-stage introduction of the sensitive triene side chain by use of Pd(PPh(3))(4)/CuCl/LiCl-promoted Stille coupling. The ABC ring fragment 5 was synthesized in a linear manner (B --> AB --> ABC), wherein the A ring was formed by intramolecular hetero-Michael reaction and the C ring was constructed via 6-endo cyclization of hydroxy epoxide 7. An improved synthetic entry to the EFGH ring fragment 6 is also described, in which SmI(2)-induced reductive cyclization methodology was applied to the stereoselective construction of the F and H rings, leading to 6 with remarkable overall efficiency. Stereoselective hydroboration of 5 and subsequent Suzuki-Miyaura coupling with 6 provided endocyclic enol ether 45 in high yield, which was then converted to octacyclic polyether core 4. Careful choice of the global deprotection stage was a key element for the successful total synthesis. Functionalization of the H ring and global desilylation gave (Z)-vinyl bromide 2. Finally, cross-coupling of 2 with (Z)-vinyl stannane 3 under Corey's Pd(PPh(3))(4)/CuCl/LiCl-promoted Stille conditions completed the total synthesis of (-)-gambierol (1).",10.1021/ja028167a,2002-11-20,0.685264700760701
Journal of the American Chemical Society,An Efficient Approach to <i>Aspidosperma </i>Alkaloids via [4 + 2] Cycloadditions of Aminosiloxydienes:  Stereocontrolled Total Synthesis of (±)-Tabersonine. Gram-Scale Catalytic Asymmetric Syntheses of (+)-Tabersonine and (+)-16-Methoxytabersonine. Asymmetric Syntheses of (+)-Aspidospermidine and (−)-Quebrachamine,"Described is a concise, highly stereocontrolled strategy to the Aspidosperma family of indole alkaloids, one that is readily adapted to the asymmetric synthesis of these compounds. The strategy is demonstrated by the total synthesis of (+/-)-tabersonine (rac-1), proceeding through a 12-step sequence. The basis for this approach was provided by a highly regio- and stereoselective [4 + 2] cycloaddition of 2-ethylacrolein with 1-amino-3-siloxydiene developed in our laboratory. Subsequent elaboration of the initial adduct into the hexahydroquinoline DE ring system was accomplished efficiently by a ring-closing olefin metathesis reaction. A novel ortho nitrophenylation of an enol silyl ether with (o-nitrophenyl)phenyliodonium fluoride was developed to achieve an efficient, regioselective introduction of the requisite indole moiety. The final high-yielding conversion of the ABDE tetracycle into pentacyclic target rac-1 relied on intramolecular indole alkylation and regioselective C-carbomethoxylation. Our approach differs strategically from previous routes and contains built-in flexibility necessary to access many other members of the Aspidosperma family of indole alkaloids. The versatility of the synthetic strategy was illustrated through the asymmetric syntheses of the following Aspidosperma alkaloids: (+)-aspidospermidine, (-)-quebrachamine, (-)-dehydroquebrachamine, (+)-tabersonine, and (+)-16-methoxytabersonine. Of these, (+)-tabersonine and (+)-16-methoxytabersonine were synthesized in greater than 1-g quantities and in enantiomerically enriched form ( approximately 95% ee). The pivotal asymmetry-introducing step was a catalyzed enantioselective Diels-Alder reaction, which proceeded to afford the cycloadducts in up to 95% ee. Significantly, the synthetic sequence was easy to execute and required only four purifications over the 12-step synthetic route.",10.1021/ja017863s,2002-04-06,0.6852601075031345
Organic Process Research & Development,Efficient and Scalable Asymmetric Total Synthesis of (−)-Emetine with Pharmaceutical Grade Quality; First Multigram Scale Synthesis,"A scalable asymmetric total synthesis of (−)-emetine, a natural product alkaloid from ipecac species and one of the main active ingredients in ipecac syrup used in emetics, has been accomplished. The synthetic route featured a total of 13 steps of highly efficient chemical reactions, including catalytic asymmetric allylation and an industrial deoxygenation of an aliphatic compound, which obviated the need for any chromatographic purification. (−)-Emetine·2HCl was obtained in 12% overall yield and over 93.2% HPLC purity. The synthesis was easily scaled up to 237.1 g and should be amenable to the production of larger quantities for ongoing drug development, while the compound is currently provided as natural ipecac syrup for a clinical use.",10.1021/acs.oprd.2c00355,2023-01-24,0.6850921896544848
Journal of Organic Chemistry,Enantioselective Total Synthesis of (−)-Limaspermidine and Formal Synthesis of (−)-1-Acetylaspidoalbidine,Evolution of the synthetic strategy\nthat culminated in the first asymmetric total synthesis of the Aspidosperma alkaloid limaspermidine is described.\nThe successful enantioselective route to (−)-limaspermidine\nproceeds in 10 steps and with the isolation of only six intermediates\nusing a Pd-catalyzed enantioselective decarboxylative allylation we\nhave recently developed. This first enantioselective synthesis of\n(−)-limaspermidine establishes unambiguously its absolute configuration\nand allows the first asymmetric formal total synthesis of the Aspidoalbine alkaloid (−)-1-acetylaspidoalbidine.,10.1021/jo4027462,2013-12-26,0.6850797820422243
Organic Process Research & Development,Synthesis of HIV Protease Inhibitor ABT-378 (Lopinavir),"A large scale process for the synthesis of HIV protease inhibitor candidate ABT-378 has been developed which utilizes an intermediate common to the synthesis of ritonavir, Abbott's first generation compound. The synthesis relies on the sequential acylation of this intermediate which is carried through as a mixture of diastereomers until the penultimate step. A synthesis of acid 5, derived from l -valine, is also reported.",10.1021/op990202j,2000-05-27,0.6850773185711416
Journal of the American Chemical Society,Total Synthesis of (−)-Dictyostatin,"A convergent total synthesis of dictyostatin is described. Key features of the synthesis include the use of titanium-mediated cyclizations of (silyloxy)enynes for the synthesis of stereotriads, a subunit coupling by metathesis, and macrocyclization by intramolecular Horner-Wadsworth-Emmons olefination.",10.1021/ja0609708,2006-04-01,0.6850040501027564
Journal of Organic Chemistry,Intramolecular Carbolithiation as a Route to a Sterically Congested Cyclopentene: Synthesis of the Longtailed Mealybug Pheromone,"A concise preparation of the pheromone secreted by the female longtailed mealybug [viz., 2-(1,5,5-trimethylcyclopent-2-en-1-yl)ethyl acetate] (1) is described. The key step in the synthesis of 1 involves 5-exo-trig ring closure of the vinyllithium derived from (Z)-1-iodo-4,4,5-trimethyl-1,5-hexadiene by lithium-iodine exchange.",10.1021/jo4002118,2013-03-07,0.684994502094193
Journal of the American Chemical Society,Ir-Catalyzed Asymmetric Total Synthesis of (−)-Communesin F,"The first catalytic asymmetric total synthesis of the heptacyclic alkaloid (-)-communesin F is described. A key step features an iridium-catalyzed asymmetric intermolecular cascade cyclization, constructing the lower N,N-aminal-containing CDEF tetracyclic core in one step. Another notable element is the closure of final ring system (A ring) via a facile reduction of a twisted amide and concomitant cyclization activated by mesylation of N,O-hemiaminal intermediate.",10.1021/jacs.7b00854,2017-02-21,0.6849621196730604
Organic Process Research & Development,Enantioselective Synthesis of Savolitinib: Application of Mosher’s Method in the Development of Ellman’s Auxiliary-Directed Construction of the Key Chiral Amine Fragment,"An efficient rational synthesis of ( S )-1-(imidazo[1,2- a ]pyridin-6-yl)ethan-1-amine via Ellman’s auxiliary approach and elaboration of this key chiral intermediate into the anticancer drug Savolitinib has been described. An apt combination of Ellman’s sulfinamide and reducing agent afforded high levels of diastereofacial control during hydride addition and secured the desired S configuration in the intermediate, which was unambiguously verified by application of Mosher’s amide method. Our nine-step synthetic sequence to Savolitinib commences with commercially available 6-amino-nicotinic acid and was first demonstrated as a proof-of-concept study on a lab scale. It was then refined during scale-up to allow telescoping of six stages and afford the final API Savolitinib with >99% chiral purity.",10.1021/acs.oprd.4c00446,2025-04-21,0.684959955246727
Journal of Organic Chemistry,Total Synthesis of Cladosins B and C,"A convergent synthetic route to the fungal metabolites cladosins B and C has been developed, affording these natural products in 29% and 27% overall yield, respectively. The cladosins are rare examples of hybrid polyketides featuring a 3-enamine tetramic acid group derived from l -valine. Key steps in this modular six-step sequence include a DMAP-mediated O - to C -acyl rearrangement to unite the side chains with the tetramic acid core and subsequent amine incorporation using either ammonium acetate or HMDS.",10.1021/acs.joc.0c01605,2020-08-05,0.6849592797403717
Organic Process Research & Development,Claisen Condensation as a Facile Route to an α-Alkoxy-cinnamate:  Synthesis of Ethyl (2<i>S</i>)-2-Ethoxy-3-(4-hydroxyphenyl)propanoate,The title compound was prepared from p -anisaldehyde and ethyl ethoxyacetate via a racemic synthetic route. The synthesis involves a Claisen-type condensation in which the elimination was unexpectedly promoted by an excess of the ester. The process has been successfully performed on a 2000-L scale with a total yield over seven steps of 19%.,10.1021/op040006z,2004-10-21,0.6849091265979896
Synlett,Efficient Enantioselective Total Synthesis of<i>arabino</i>-Phytosphingosine,"Enantioselective total synthesis of arabino-phytosphingosine has been achieved in 8 steps employing Claisen rearrangement and Fleming-Tamao oxidation as key steps. Installation of all chiral centers present in arabino-phytosphingosine was achieved through the use of asymmetric catalysis. This synthesis provides one of the most efficient routes to prepare 2-amino-1,3,4-triol moiety.",10.1055/s-2005-872242,2005-01-01,0.6848798939174641
Synthesis,Selective Synthesis of <b><i>ent</i></b>-15-<b><i>epi</i></b>-F<sub>2t</sub>-Isoprostane and a Deuterated Derivative,"Isoprostanes are an emerging class of lipid metabolites whose physiological properties are not well understood. The selective synthesis of ent-15-epi-F2t-isoprostane, an isomer active in a preliminary screening assay is described. The synthesis features a regioselective cross-metathesis on an enantiomerically enriched divinyl cyclopentyl intermediate to selectively differentiate the side-chains of the target. The route provides the isoprostane, as well as a d 4-labeled analogue, in 14 steps from readily available starting material­s.",10.1055/s-2007-983768,2007-07-01,0.68479391143645
Organic Letters,First Total Synthesis of (−)-Achilleol B: Reassignment of Its Relative Stereochemistry,"The first total synthesis of (-)-achilleol B was achieved using a convergent approach with a longest linear sequence of 14 steps. Three key steps were employed, including an enantioselective Robinson annelation for the construction of the bicyclic moiety. The monocyclic synthon was prepared through a Ti(III)-mediated cylization of a chiral monoepoxide obtained via asymmetric dihydroxylation of geranylacetone. The asymmetric preparation of these subunits also permitted us to achieve the enantioselective synthesis of elegansidiol, achilleol A, and farnesiferol B.",10.1021/ol800326n,2008-04-02,0.6847909224497107
Journal of the American Chemical Society,Asymmetric Synthesis of the Highly Potent Anti-Metastatic Prostacyclin Analogue Cicaprost and Its Isomer Isocicaprost,"An asymmetric synthesis of the anti-metastatic prostacyclin analogue cicaprost and a formal one of its isomer isocicaprost by a new route are described. A key step of these syntheses is the coupling of a chiral bicyclic C6-C14 ethynyl building block with a chiral C15-C21 omega-side chain amide building block with formation of the C14-C15 bond of the target molecules. A highly stereoselective reduction of the thereby obtained C6-C21 intermediate carrying a carbonyl group at C15 of the side chain was accomplished by the chiral oxazaborolidine method. The chiral phosphono acetate method was used for the highly stereoselective attachment of the alpha-side chain to the bicyclic C6-C21 intermediate carrying a carbonyl group at C6. Asymmetric syntheses of the bicyclic C6-C14 ethynyl building blocks were carried out starting from achiral bicyclic C6-C12 ketones by using the chiral lithium amide method. In the course of these syntheses, a new method for the introduction of an ethynyl group at the alpha-position of the carbonyl group of a ketone with formation of the corresponding homopropargylic alcohol was devised. Its key steps are an aldol reaction of the corresponding silyl enol ether with chloral and the elimination of a trichlorocarbinol derivative with formation of the ethynyl group. In addition, a new aldehyde to terminal alkyne transformation has been realized. Its key steps are the conversion of an aldehyde to the corresponding 1-alkenyl dimethylaminosulfoxonium salt and the elimination of the latter with a strong base. Two basically different routes have been followed for the synthesis of the enantiomerically pure C15-C21 omega-side chain amide building block. The first is based on the chiral oxazolidinone method and features a highly stereoselective alkylation of (4R)-N-acetyl-4-benzyloxazolidin-2-one, and the second encompasses a malonate synthesis of the racemic amide and its efficient preparative scale resolution by HPLC on a chiral stationary phase containing column.",10.1021/ja030200l,2003-07-19,0.684737017729903
Tetrahedron,"An expedient route to the preparation of key intermediates for the total synthesis of aphidacolin, stemodin and oryzalexin S",,10.1016/0040-4039(96)01875-8,1996-11-01,0.6847147732796416
Organic Process Research & Development,Efficient Synthesis of a Key Intermediate for Baloxavir Marboxil from a Greener Starting Material: Ethylene Glycol,"In this article, a robust and scalable process to prepare the key intermediate 7-(benzyloxy)-3,4,12,12a-tetrahydro-1 H -[1,4]oxazino[3,4- c ]pyrido[2,1- f ][1,2,4]triazine-6,8-dione ( 1 ) for the synthesis of the influenza antiviral drug baloxavir marboxil is described. The process is based on a novel preparation of 2-(2,2-dimethoxyethoxy)ethanamine 5 employing inexpensive and readily available ethylene glycol as the starting material with more convenient manipulation and fewer environmental hazards compared with the original routes starting with ethanolamine or its derivatives. Large-scale applicability of this new route has been successfully demonstrated on kilogram-scale production to afford 700 grams of 1 with 99.3% purity in 31% yield over six steps. With such satisfactory quality, baloxavir marboxil is eventually furnished with excellent purity (>99.5%, single impurity < 0.1%). Meanwhile, the corresponding impurity profile is studied in detail.",10.1021/acs.oprd.1c00141,2021-09-08,0.6847114555834831
Organic Process Research & Development,Commercial Synthesis of a Pyrrolotriazine–Fluoroindole Intermediate to Brivanib Alaninate: Process Development Directed toward Impurity Control,"The development of a practical, commercial process for the preparation of 4-fluoro-2-methyl-indol-5-ol and its subsequent coupling with a pyrrolotriazine to form an advanced intermediate of the oncology therapy brivanib alaninate is described. A key aspect is the multikilogram-scale preparation of the fluoroindole intermediate from trifluoronitrobenzene and the subsequent coupling while achieving impurity minimalization. As brivanib alaninate is a high-dose drug, the synthesis of high-quality API with low levels of impurities is critical.",10.1021/op400242j,2013-12-02,0.684677798890234
European Journal of Organic Chemistry,Neighbouring-Group Assisted Thiazole-Ring Cleavage by DIBAL-H: An Expeditious Synthesis of Melithiazol C from Myxothiazol A,The semi-synthesis of melithiazol C (2b) has been accomplished in 4 steps and 41% overall yield starting from myxothiazol A (1a) produced by fermentation of Myxococcus fulvus. Key steps are a novel reductive cleavage of a thiazole ring by DIBAL-H and the conversion of the amide 2a into the methyl ester 2b via an imino ester. The biological activities of 2b and of derivatives of its 10-acetyl group are described.,10.1002/1099-0690(200006)2000:11<2021::aid-ejoc2021>3.0.co;2-k,2000-06-01,0.6846775323079345
European Journal of Organic Chemistry,Neighbouring-Group Assisted Thiazole-Ring Cleavage by DIBAL-H: An Expeditious Synthesis of Melithiazol C from Myxothiazol A,The semi-synthesis of melithiazol C (2b) has been accomplished in 4 steps and 41% overall yield starting from myxothiazol A (1a) produced by fermentation of Myxococcus fulvus. Key steps are a novel reductive cleavage of a thiazole ring by DIBAL-H and the conversion of the amide 2a into the methyl ester 2b via an imino ester. The biological activities of 2b and of derivatives of its 10-acetyl group are described.,10.1002/1099-0690(200006)2000:11<2021::aid-ejoc2021>3.3.co;2-b,2000-06-01,0.6846775323079345
Organic Process Research & Development,"Development of a Practical and Scalable Synthetic Route for the Adenosine Monophosphate-Activated Protein Kinase Activator, ASP4132","This paper describes the research and development of a practical and efficient process for making the adenosine monophosphate-activated protein kinase (AMPK) activator, ASP4132 ( 1 ). The newly developed process includes an efficient telescoping process consisting of Suzuki–Miyaura coupling and hydrogenation, effective removal of palladium using N -acetyl cysteine and silica gel, and reductive amination with the stable and mild reducing reagent, 2-picoline borane. The need for chromatographic purification was removed from all steps. The overall yield improved from 18% in the medicinal synthetic route to 43% using the new procedure. This highly efficient process was successfully demonstrated on a pilot scale to yield ASP4132 ( 1 ) with high quality.",10.1021/acs.oprd.1c00392,2021-12-09,0.684638999853817
Tetrahedron,A concise route to biaryls : Formal synthesis of biaryl diamino diacid (AB segment) of vancomycin,,10.1016/s0040-4039(00)73314-4,1994-07-01,0.6845772433970576
Organic Letters,Synthesis of the Natural Product Marthiapeptide A,"The first total synthesis of marthiapeptide A is reported. Two synthetic procedures are described: the first, which was unsuccessful, attempts to close the ring at position I, and the second, which was successful, closes the ring at position II. It appears that the first route was unsuccessful because it required cyclization next to the rigid thiazole moiety, whereas the second route closed next to the more flexible thiazoline ring.",10.1021/acs.orglett.5b02574,2015-10-15,0.6845600798837627
Tetrahedron,New efficient synthesis of furanoacetylene phytoalexins wyerone and dihydrowyerone,,10.1016/s0040-4039(00)60442-2,1993-04-01,0.6845063920644531
Tetrahedron,A new efficient resveratrol synthesis,,10.1016/s0040-4039(01)02227-4,2002-01-01,0.6845063920644531
Tetrahedron,A new efficient synthesis of 3-(4-pyridinyl)methylindoles,,10.1016/s0040-4039(01)01525-8,2001-10-01,0.6845063920644531
Tetrahedron,New efficient and flexible synthesis of polysubstituted pyrroles,,10.1016/0040-4039(95)01717-v,1995-10-01,0.6845063920644531
Tetrahedron,"A new efficient synthesis of (5S,12S)-DiHETE",,10.1016/s0040-4039(00)79056-3,1992-05-01,0.6845063920644531
Tetrahedron,A new efficient synthesis of β-aminoketones via Δ4-isoxazolines.,,10.1016/s0040-4039(00)82225-x,1988-01-01,0.6845063920644531
Journal of Organic Chemistry,Total Synthesis of (±)-Sarracenin,A total synthesis of (+/-)-sarracenin (1) is described. The key steps include (1) regioselective ring expansion of 7 to bicyclo[3.2.1]ketone6 and (2) ring opening of tricyclic ketone 5 to ester 4.,10.1021/jo961734q,1997-02-01,0.684460562554299
Journal of the American Chemical Society,Strategy in Oligosaccharide Synthesis:  An Application to a Concise Total Synthesis of the KH-1(adenocarcinoma) Antigen,"A concise and potentially practical synthesis of the title compound has been achieved. The route features a high degree of convergence and economy of synthetic operations. A key step is the concurrent introductory addition of three α- l -fucosyl residues at required hydroxyl acceptor sites (see 37 → 39 ). Conjugation to carrier protein was achieved, and a route to include truncated structures for investigations for antibody specificity was accomplished.",10.1021/ja9725864,1998-02-01,0.6844550128847815
Organic Letters,"Highly Efficient Chiral-Pool Synthesis of (2<i>S</i>,4<i>R</i>)-4-Hydroxyornithine","[reaction: see text] A concise synthesis of the amino acid (2S,4R)-4-hydroxyornithine is described. Starting from diprotected L-aspartic acid, the scaffold of the target compound is constructed in a three-step approach: an efficient alpha-nitroketone formation through acylation of nitromethane is followed by a diastereoselective reduction of the resulting ketone. In the last step, the nitro group is reduced to furnish the (2S,4R)-4-hydroxyornithine scaffold. This new approach to the title compound offers advantages to the synthetic pathways previously described.",10.1021/ol016445p,2001-09-05,0.6844544781676031
Synthesis,"Improved Synthesis of a Selective COX-2 Inhibitor, 6-(2,4-Difluorophenoxy)-5-methanesulfonamidoindan-1-one (Flosulide)","All articles of this category An improved synthesis of Flosulide (1) , a selective COX-2 inhibitor, from the cheap and commercially available 4-chloro-3-nitrobenzaldehyde (2) by using an intramolecular Friedel-Crafts reaction of 4-(2,4-difluorophenoxy)-3-methanesulfonamidophenylpropionic acid (7) as the key step is reported. COX-2 inhibitor - intramolecular Friedel-Crafts reaction - Flosulide",10.1055/s-1995-4129,1995-11-01,0.6844139556947181
Journal of Organic Chemistry,Total Synthesis of (+)-Astrophylline,"The first total synthesis of (+)-astrophylline (2) has been achieved, starting from readily available enantiomerically pure (+)-(1R,4S)-4-hydroxycyclopent-2-enyl acetate (11). A novel ruthenium-catalyzed ring-closing ring-opening ring-closing metathesis of carbocyclic olefins of general type 5 was the key step, providing the stereochemically well-defined bis-piperidyl skeleton of the target molecule. A [2,3]-Wittig-Still rearrangement of 9 was also employed as the critical transformation in the stereocontrolled generation of the 1,2-trans configuration of the cyclopentene intermediate 6c. Our early synthetic efforts toward 1,2-trans cyclopentene derivatives of type 6, as well as the synthetic pathway to an optimized 13-step total synthesis of 2 (12% overall yield), are reported.",10.1021/jo026803h,2003-03-07,0.68434634565619
Journal of the American Chemical Society,Total Synthesis of (+)-Phorboxazole A Exploiting the Petasis−Ferrier Rearrangement,"A highly convergent, stereocontrolled total synthesis of the potent antiproliferative agent (+)-phorboxazole A (1) has been achieved. Highlights of the synthesis include: modified Petasis-Ferrier rearrangements for assembly of both the C(11-15) and C(22-26) cis-tetrahydropyran rings; extension of the Julia olefination to the synthesis of enol ethers; the design, synthesis, and application of a novel bifunctional oxazole linchpin; and Stille coupling of a C(28) trimethyl stannane with a C(29) oxazole triflate. The longest linear sequence leading to (+)-phorboxazole A (1) was 27 steps, with an overall yield of 3%.",10.1021/ja011604l,2001-10-13,0.6843360422304663
Organic Letters,Enantioselective Total Synthesis of Pladienolide B: A Potent Spliceosome Inhibitor,"An enantioselective and convergent total synthesis of pladienolide B (1) is described. Pladienolide B binds to the SF3b complex of a spliceosome and inhibits mRNA splicing activity. The synthesis features an epoxide opening reaction, an asymmetric reduction of a β-keto ester, and a cross metathesis strategy for the side chain synthesis.",10.1021/ol301886g,2012-09-06,0.684255798619552
Organic Letters,Concise Total Synthesis of (−)-8-Epigrosheimin,"A highly efficient route was developed to synthesize (-)-8-epigrosheimin in four steps from aldehyde 2 based on a substrate-controlled method. The key steps of the synthesis included (1) a stereo- and regioselective allylation addition, (2) an intramolecular translactonization, and (3) an aldehyde-ene cyclization.",10.1021/ol201322w,2011-06-15,0.6842437139715299
Organic Letters,"Total Synthesis of (±)-Joubertinamine from 3-(3,4-Dimethoxyphenyl)-5-bromo-2-pyrone","The regioselective synthesis and Diels-Alder cycloaddition of 3-(3,4-dimethoxyphenyl)-5-bromo-2-pyrone provided a new efficient synthetic route to joubertinamine (9.6% total yield over 10 steps).",10.1021/ol071381p,2007-07-28,0.6842179052920463
Organic Letters,Total Synthesis of (±)-Hasubanonine,"[reaction: see text] Total synthesis of the alkaloid (+/-)-hasubanonine is described. A key feature of the route is generation of a phenanthrene intermediate via a Suzuki coupling-Wittig olefination-ring-closing metathesis sequence. Conversion of the phenanthrene into the target molecule required six steps including dearomatization by means of oxidative phenolic coupling, anionic oxy-Cope rearrangement, and a final acid-promoted cyclization. Production of an undesired rearranged product in the last step could be suppressed by moderating the acid strength.",10.1021/ol0613564,2006-07-15,0.6841728037856576
Organic Process Research & Development,"Synthesis of a Substance P Antagonist:  An Efficient Synthesis of 5-Substituted-4-<i>N,N</i>-dimethylamino-1,2,3-triazoles","A highly efficient synthesis of the substance P antagonist 1 is reported starting from the optically pure morpholine acetal derivative 2 . The 5-dimethylaminomethyl-1,2,3-triazole moiety is elaborated via a 1,3-dipolar cycloaddition between an activated acetylenic intermediate and sodium azide. Two approaches to the construction of the triazole moiety of 1 have been designed. The first approach is linear affording the side chain in four steps and 85−92% overall yield. The reactive acetylenic aldehyde 5 allowed for a mild azide cyclization. A simple reductive amination of the triazole aldehyde completed the synthesis of 1 . An alternative, more efficient, convergent synthesis using analogous methodology developed from the linear synthesis was designed to improve the overall efficiency of the process as well as remove the concerns with the handling of azide. The triazole adduct was prepared offline in a two-step, one-pot operation as the building block 4- N,N -dimethylaminomethyl-1,2,3-triazole-aldehyde 3 . Formylation of N,N -dimethylaminopropyne and azide cyclization were carried out as a through process to afford the triazole aldehyde 3 in 90% assay yield. The product was isolated in overall yields ranging from 67 to 81% depending on method. The aldehyde group of 3 was used for coupling to the morpholine building block through a reductive amination with NaBH(OAc) 3 in near quantitative yield to afford the substance P antagonist 1 as a hydrochloride salt in 95% yield from 2 .",10.1021/op050019s,2005-06-14,0.6841372715137404
Journal of the American Chemical Society,Total Synthesis of Thailanstatin A,"The total synthesis of the spliceosome inhibitor thailanstatin A has been achieved in a longest linear sequence of nine steps from readily available starting materials. A key feature of the developed synthetic strategy is the implementation of a unique, biomimetic asymmetric intramolecular oxa-Michael reaction/hydrogenation sequence that allows diastereodivergent access to highly functionalized tetrahydropyrans, which can be used for the synthesis of designed analogues of this bioactive molecule.",10.1021/jacs.6b04781,2016-06-08,0.6840922935918419
Organic Process Research & Development,Scale-Up Preparation of Best-In-Class Orally Bioavailable CXCR4 Antagonist EMU-116 in an Academic Setting,"High Resolution Image Download MS PowerPoint Slide CXCR4 is a seven-transmembrane chemokine receptor that is intimately involved in stem cell niche maintenance and immune cell trafficking. Among several other pathophysiological states for which CXCR4 mis regulation is implicated, various hematological malignancies and solid tumors hijack this chemokine network by dramatically overexpressing CXCR4 and its cognate chemokine ligand CXCL12. Upregulation of the CXCR4/CXCL12 axis in cancer drives tumor progression through several mechanisms, which makes CXCR4 a promising target for the development of anticancer therapeutics. Herein, we report the preparative scale synthesis of a novel, best-in-class, orally bioavailable small molecule CXCR4 antagonist, EMU-116. Two synthetic strategies for production of EMU-116 were pursued. While the first discovery-focused synthesis facilitated late-stage diversification to drive structure–activity relationship determinations, the second process-focused synthesis delivered EMU-116 more efficiently in higher overall yield with enhanced stereocontrol. For both synthetic routes, Buchwald–Hartwig amination of key aryl bromide intermediates enabled installation of the N -methylpiperazine appendage of EMU-116. Synthetic methods devised to prepare ( R )-9-bromo-1,5,10,10 a -tetrahydro-3 H -oxazolo[3,4 -b ]isoquinolin-3-one, the key aryl bromide intermediate required for the process-focused synthesis, are reported. In addition, an improved preparative method of known synthon ( S )– N -methyl-5,6,7,8-tetrahydroquinolin-8-amine is highlighted by elevated overall yield, enhanced diastereoselectivity, and robust purification by crystallization. Further elaboration of these two intermediates, coupling via reductive amination to furnish the full EMU-116 scaffold, removal of protecting groups, and final product purification techniques are also reported. Overall, the synthetic methods described herein enabled reliable and efficient production of multigram quantities of EMU-116 and are anticipated to be amenable to larger scale production.",10.1021/acs.oprd.4c00246,2024-10-18,0.6840776348472248
Journal of Organic Chemistry,"Efficient Methodology for the Synthesis of 3-Amino-1,2,4-triazoles","A general and efficient method for the preparation of 3-amino-1,2,4-triazoles has been developed. The desired 3-amino-1,2,4-triazoles (1) were prepared in good overall yield via two convergent routes. The key intermediate within both routes is substituted hydrazinecarboximidamide derivative 2.",10.1021/jo9016502,2009-09-04,0.6840749755978992
Organic Process Research & Development,"Efficient Synthesis of <i>N-tert</i>-Butyl-2-{3(<i>R</i>)-[3-(3-chlorophenyl)ureido]- 8-methyl-2-oxo-5(<i>R</i>)-phenyl-1,3,4,5-tetrahydrobenz[<i>b</i>]azepin-1-yl}acetamide and Related CCK<sub>B</sub> Antagonists","An efficient synthesis of the CCK B antagonist N - tert -butyl-2-{3( R )-[3-(3-chlorophenyl)ureido]-8-methyl-2-oxo-5( R )-phenyl-1,3,4,5-tetrahydrobenz[ b ]azepin-1-yl}acetamide [( R )- 1a ] in optically active form is presented. The synthesis of the core 3-amino-5-phenylbenzazepin-2-one moiety started with the coupling of 2-amino-4-methylbenzophenone ( 6a ) and diethyl 3-phosphono-2-(methoxyimino)propionic acid ( 8 ). The resulting amide diethyl 2-[3-phosphono-2-(methoxyimino)propionamido]-4-methylbenzophenone ( 9a ) underwent intramolecular benzazepinone ring formation in tetrahydrofuran with 2 equiv of potassium tert -butoxide to provide 8-methyl-5-phenyl-1 H -benz[ b ]azepine-2,3-dione 3-( O -methyloxime) ( 10a ) in high yield. Hydrogenation over Raney nickel in methanol reduced both the O -methyloxime and the 4,5-double bond, giving cis -3-amino-8-methyl-5-phenyl-1,3,4,5-tetrahydrobenz[ b ]azepin-2-one ( 7a ) with high selectivity. A classical resolution of amino lactam 7a and attachment of the N-1 and C-3 side chains afforded the title compound. The sequence was repeated with other 2-aminophenyl ketones and was shown to work well for C-5 substituents such as methyl and cyclohexyl or as part of a fluorenyl group, thus providing an easy access to these molecules from readily available starting materials.",10.1021/op9702049,1997-03-01,0.6840577636746688
Synlett,A Synthesis of (-)-cis-2-Aminomethylcyclopropanecarboxylic Acid [(-)-CAMP],"An enantioselective synthesis of (–)- cis -2-aminomethylcyclopropanecarboxylic acid [(–)-CAMP] has been achieved in 2.5% total yield over ten steps starting from 2-furaldehyde. The synthesis features diastereoselective cyclopropane formation via diazene, followed by oxime formation and the reduction, for construction of the γ-aminobutyric acid (GABA) motif.",10.1055/s-0032-1317802,2013-03-15,0.6840326534473269
Organic Process Research & Development,Practical Synthesis of Ethyl 3-Fluoro-1-pyrrole-2-carboxylate: A Key Fragment of a Potent Drug Candidate against Hepatitis B Virus,We report herein the development of two efficient synthetic routes for the preparation of a key fragment required for the synthesis of potent drug candidates of Hepatitis B virus. The ethyl 3-fluoro-1- H -pyrrole-2-carboxylate scaffold was synthesized from readily available starting materials in good overall yields. The scalability of one of the developed routes was demonstrated and afforded the desired target in good yield and excellent purity (99%).,10.1021/acs.oprd.9b00382,2019-09-26,0.6840273492496777
Synthesis,"An Efficient Synthesis of ABT-263, a Novel Inhibitor of Antiapoptotic Bcl-2 Proteins","ABT-263, a newly developed Bcl-2 inhibitor, was efficiently synthesized. The key intermediates 4-(4-{[2-(4-chlorophenyl)-5,5-dimethylcyclohex-1-enyl]methyl}piperazin-1-yl)benzoic acid and 4-fluoro-3-[(trifluoromethyl)sulfonyl]benzenesulfon­amide were efficiently prepared by a three-component Mannich reaction­ and by nucleophilic fluorination of 1-nitro-2-[(trifluoro­methyl)sulfonyl]benzene as the key steps, respectively. Our work may lay a foundation for a new process development of this promising anticancer drug candidate.",10.1055/s-2008-1067129,2008-06-11,0.6839203614010719
Organic Process Research & Development,Development of a Robust and Scalable Synthetic Route for a Potent and Selective Isoindolinone PI3Kγ Inhibitor,"We recently described the structure-guided optimization of a series of pyrazolopyrimidine isoindolinone PI3Kγ inhibitors, which resulted in the identification of an advanced lead compound ( 1 ) with favorable potency, selectivity, and drug-like properties. To support preclinical characterization of 1, a robust and scalable synthesis was required. Herein, we report the development of an optimized synthesis of 1, which features a scalable difluoromethylation protocol and a one-pot borylation/Suzuki–Miyaura cross-coupling reaction to access the biaryl core of the molecule. A method was developed for the efficient removal of residual palladium following Pd-catalyzed cross-coupling, which provided access to 1 in high purity without the use of any chromatographic purifications. A comprehensive investigation of solid-state polymorphism identified a thermodynamically stable crystalline form of 1, greater than 200 g of which were prepared using our optimized synthesis.",10.1021/acs.oprd.2c00240,2022-09-28,0.6838745520544103
Tetrahedron,First synthesis of picealactone C. A new route toward taxodione-related terpenoids from abietic acid,,10.1016/j.tetlet.2006.12.009,2006-12-23,0.6838554796374238
Organic Letters,Total Synthesis of Kasugamycin,"We present an efficient synthetic pathway for kasugamycin, an aminoglycoside antibiotic, utilizing naturally derived carbohydrates as starting materials. This synthesis effectively addresses stereochemical complexities by employing the selective reduction of d -fucal, which generates a crucial 3-deoxyglycal intermediate. This intermediate facilitates the introduction of amino groups at the C-2 and C-4 positions, which is essential for the synthesis of kasugamine. Subsequent glycosylation with glycosyl 1- O - m -chlorobenzoate ( m CBz) donors yields a disaccharide intermediate, which is further transformed to produce kasugamycin. This streamlined approach provides a practical and effective route for the synthesis of kasugamycin and related deoxy amino sugar-containing antibiotics.",10.1021/acs.orglett.4c04545,2025-01-08,0.683830463042409
Organic Process Research & Development,Development of an Efficient and Stereoselective Manufacturing Route to Idoxifene,"A literature route to 1-(2-{4-[( E )-1-(4-iodophenyl)-2-phenyl-but-1-enyl]phenoxy}ethyl)pyrrolidine (idoxifene) has been modified to tackle various scale-up issues and provide initial supplies. A new highly efficient, robust, and stereoselective manufacturing route is described in detail. This route involves diastereoselective synthesis of tertiary alcohol (1 RS,2 SR )-1-(4-iodophenyl)-2-phenyl-1-[4-(2-pyrrolidin-1-yl-ethoxy)phenyl]butan-1-ol by Grignard addition to the ketone 1-(4-iodophenyl)-2-phenyl-1-butanone followed by derivatisation and stereoselective syn elimination to provide idoxifene in excellent yield and geometric purity. Evaluation of a more direct route to idoxifene using a McMurry low-valent titanium coupling reaction is also described.",10.1021/op0100394,2001-08-22,0.6838251590929025
Tetrahedron,An asymmetric dihydroxylation route to (S)-oxybutynin,,10.1016/s0040-4039(03)00886-4,2003-05-01,0.6838210604273969
Organic Letters,Total Synthesis of Stachyodin A via One-Pot Suzuki Coupling for Quick Construction of Carbon Skeleton,"Stachyodin A, possessing a unique spirotetrahydrofuran ring system, was isolated from the roots of Indigofera stachyodes in 2018. The first total synthesis of racemic stachyodin A was accomplished in 14 steps. The efficient stereoselective synthetic route involved one-pot Suzuki coupling and stereocontrolled epoxidation followed by reductive opening and spirocyclization.",10.1021/acs.orglett.1c00998,2021-05-12,0.6838108402924349
Organic Process Research & Development,A Novel and Practical Synthesis of Ramelteon,"An efficient and practical process for the synthesis of ramelteon 1, a sedative-hypnotic, is described. Highlights in this synthesis are the usage of acetonitrile as nucleophilic reagent to add to 4,5-dibromo-1,2,6,7-tetrahydro-8 H -indeno[5,4- b ]furan-8-one 2 and the subsequent hydrogenation which successfully implement four processes (debromination, dehydration, olefin reduction, and cyano reduction) into one step to produce the ethylamine compound 13 where dibenzoyl- l -tartaric acid is selected both as an acid to form the salt in the end of hydrogenation and as the resolution agent. Then, target compound 1 is easily obtained from 13 via propionylation. The overall yield in this novel and concise process is almost twice as much as those in the known routes, calculated on compound 2 .",10.1021/op500386g,2015-01-06,0.6838096411820381
Angewandte Chemie International Edition,Total Synthesis of (+)-Lactacystin,"A double stereodifferentiating crotylation between aldehyde 1 and silane (S)-2 to afford homoallylic alcohol 3 is the key diastereoselective step (anti:syn >30:1) in an efficient asymmetric synthesis of (+)-lactacystin. This compound is a metabolite isolated from Streptomyces sp. OM-6519 that exhibits significant neurotrophic activity. An additional important step in the synthesis is a catalytic asymmetric aminohydroxylation used as the key step in the synthesis of the (2R,3S)-hydroxyleucine synthon.",10.1002/(sici)1521-3773(19990419)38:8<1093::aid-anie1093>3.0.co;2-u,1999-04-19,0.6837884026500497
Journal of Organic Chemistry,Synthesis of 5-Substituted-1<i>H</i>-indol-2-yl-1<i>H</i>-quinolin-2-ones:  A Novel Class of KDR Kinase Inhibitors,"[reaction: see text] A number of approaches for the synthesis of the 1H-indol-2-yl-1H-quinolin-2-one ring system found in the potent and selective KDR kinase inhibitor 1 are described. The preparation and reaction of trimethylsilylnitrobenzene 26 with 2-methoxy-3-quinolinecarboxaldehyde 28 afforded alcohol 30, which was the key intermediate for the preparation of the target compounds. Conversion of alcohol 30 to either nitroketone 36 or nitrostyrene 45 set the stage for reductive cyclization and the formation of indole 25. The quinolin-2-one functionality was unmasked in the last step to provide compound 1 in 56-60% overall yield from readily available starting materials.",10.1021/jo0480545,2005-02-25,0.6837672049495958
Synlett,"An Alternate Synthesis of Bosentan Monohydrate, an Endothelin Receptor Antagonist","An alternate synthesis of an endothelin receptor antagonist bosentan monohydrate is reported. This new synthetic route involves the coupling of p - tert -butyl- N -[6-chloro-5-(2-methoxy-phenoxy)(2,2′-bipyrimidin)-4-yl]benzene sulfonamide with commercially available raw material (2,2-dimethyl-1,3-dioxolan-4-yl)methanol as the key step. Attractive features of this approach are its versatileness, commercial availability of raw materials, usage of eco-friendly reagents, and it efficiently provides the desired bosentan monohydrate free from reported impurities such as dimer, N-alkylated, and pyrimidinone impurities.",10.1055/s-0033-1340281,2013-12-02,0.6837292985906033
Organic Process Research & Development,"Synthesis of Tetracyclic Heterocompounds as Selective Estrogen Receptor Modulators. Part 1. Process Development for Scale-up of 2,5,8-Substituted 5,11-Dihydrochromeno[4,3-<i>c</i>]chromene Derivatives","Unsymmetrical benzopyranobenzopyran compounds are novel selective estrogen receptor modulators (SERMs). A reproducible and nonchromatographic process was developed to prepare multihundred gram quantities of 5-(4-(2-(piperidin-1-yl)ethoxy)phenyl)-5,11-dihydrochromeno[4,3- c ]chromene-2,8-diyl-bis(2,2-dimethylpropanoate) ( 14 ). The overall yield of this 11-step synthesis was improved from 0.17% to 7.1% after three scale-up campaigns.",10.1021/op700020f,2007-03-31,0.6837168737398368
Synthesis,A Facile and Improved Synthesis of 3-Fluorothiophene,"A new efficient and convenient route to 3-fluoro­thiophene in four steps and 49% overall yield is reported. The fluorine atom was successfully introduced into the thiophene ring in 67% yield using the Schiemann reaction on 2-methoxycarbonyl­thiophene-3-diazonium tetrafluoroborate. The product, methyl 3-fluorothiophene-2-carboxylate was saponified and the 3-fluorothiophene-2-carboxylic acid was decarboxylated to afford 3-fluorothiophene in 93% yield.",10.1055/s-2008-1067170,2008-07-08,0.6837079543916471
Tetrahedron,"A novel asymmetric route to 2-amino-1,2,3,4-tetrahydronaphthalenes",,10.1016/s0040-4039(00)00327-0,2000-04-01,0.6836722813494825
Organic Letters,"Selective Synthesis of Epolactaene Featuring Efficient Construction of Methyl (<i>Z</i>)-2-Iodo-2-butenoate and (2<i>R</i>,3<i>S</i>,4<i>S</i>)-2-Trimethylsilyl-2,3-epoxy-4-methyl- γ-butyrolactone","[reaction: see text] (+)-Epolactaene was synthesized in 14 steps in the longest linear sequence. The synthesis is highlighted by a highly efficient preparation of the lactone intermediate 4, which only requires three steps from the commercially available (S)-3-butyn-2-ol. It also features a fully stereocontrolled synthesis of the intermediate 9, which was constructed through the use of Zr-catalyzed methylalumination of alkynes and a series of Pd-catalyzed organozinc cross-coupling reactions, such as homopropargylation, direct ethynylation, and alkenylation of the methyl ester of (Z)-alpha-iodocrotonic acid (3).",10.1021/ol060856u,2006-06-01,0.6836439284902827
Synlett,Synthesis of a Chiral Key Intermediate of Neurokinin Antagonist SSR 240600 by Asymmetric Allylic Alkylation,International audience,10.1055/s-0031-1289878,2011-11-11,0.6836198969970882
Organic Process Research & Development,Development of an Efficient Manufacturing Process for Reversible Bruton’s Tyrosine Kinase Inhibitor GDC-0853,"High Resolution Image Download MS PowerPoint Slide Efforts toward the process development of reversible Bruton’s tyrosine kinase (BTK) inhibitor GDC-0853 ( 1 ) are described. A practical synthesis of GDC-0853 was accomplished via a key highly regioselective Pd-catalyzed C–N coupling of tricyclic lactam 5 with 2,4-dichloronicotinaldehyde ( 6 ) to afford the C–N coupling product 3, a Suzuki–Miyaura cross-coupling of intermediate 3 with boronic ester 4 derived from a Pd-catalyzed borylation of tetracyclic bromide 7, to generate penultimate aldehyde intermediate 2 and subsequent aldehyde reduction and recrystallization. Process development of starting materials 5, 6, and 7 is also discussed.",10.1021/acs.oprd.8b00134,2018-07-02,0.6836037649630582
Tetrahedron,A new diastereoselective route to 5-substituted-8-methylindolizidines. Synthesis of indolizidine (−) 209B,,10.1016/s0040-4039(98)01040-5,1998-07-01,0.6835809167982776
European Journal of Organic Chemistry,Expeditious Synthesis of Ieodoglucomides A and B from the Marine‐Derived Bacterium <i>Bacillus licheniformis</i>,"We report the total synthesis of ieodoglucomides A and B. The key steps of the synthesis are a glycosyl‐iodide‐mediated β‐stereoselective glycosylation without neighbouring‐group participation, a regioselective acylation, and a Grubbs cross‐metathesis reaction. The short and efficient synthesis involves 11 steps, with 38–40 % overall yield.",10.1002/ejoc.201800209,2018-05-09,0.6835748769180334
Synlett,Practical and Efficient Route to (<i>S</i>)-γ-Fluoroleucine,"A practical and efficient route to (S)-γ-fluoroleucine was developed via compound 9. Introduction of the fluorine was achieved using N,N-diethylaminosulfur trifluoride (DAST) treatment on a tertiary alcohol 8.",10.1055/s-2005-868494,2005-05-03,0.6835235437781492
Synlett,Short-Step Total Synthesis of a Cyclopropane-Containing Eicosanoid,All articles of this category A short-step total synthesis of a cyclopropane-containing eicosanoid 1 is described. The key step was an efficient stereoselective synthesis of trans -disubstituted cyclopropane 6 via the cyclization-ozonolysis sequence. The overall yield of the seven-step synthesis was 24% from known ester 2 . marine natural products - cyclopropane-containing eicosanoid - difunctional cyclopropane - homoallylic participation,10.1055/s-1995-5189,1995-10-01,0.6835090994302097
Synthesis,"A Scalable, Chromatography-Free Synthesis of the Potent and Highly Selective ERβ Agonist EGX358",Abstract 4-[trans-4-(Hydroxymethyl)cyclohexyl]phenol (EGX358) is a potent and highly selective estrogen receptor beta (ERβ) agonist which has demonstrated efficacy for moderation of a chemically induced hot flash and for memory consolidation in an ovariectomized mouse model for menopause. An improved synthetic route to EGX358 is reported which proceeds in four steps and which is chromatography-free.,10.1055/s-0043-1775433,2025-01-22,0.683472008693205
Organic Process Research & Development,Scale-Up Synthesis of IID572: A New β-Lactamase Inhibitor,"The new potentially best-in-class β-lactamase inhibitor IID572 was discovered by a late-stage functionalization approach. An alternative synthesis was developed to satisfy the short-term material need for toxicological studies in animals. The new synthetic strategy was built on two key features, an intramolecular azomethine ylide [3 + 2] cycloaddition that allowed the efficient formation of molecular complexity from readily available starting materials and an enzymatic resolution that resulted in high optical purity of a key intermediate.",10.1021/acs.oprd.0c00069,2020-05-14,0.6834083085552011
Organic Process Research & Development,Synthesis and Process Optimization of Amtolmetin: An Antiinflammatory Agent,Efforts toward the synthesis and process optimization of amtolmetin guacil 1 are described. High-yielding electrophilic substitution followed by Wolf−Kishner reduction are the key features in the novel synthesis of tolmetin 2 which is an advanced intermediate of 1 .,10.1021/op900284w,2010-01-15,0.6833341757257864
Tetrahedron,A novel route to a 4-amino steroid: MDL 19687,,10.1016/0040-4039(95)00893-h,1995-07-01,0.6833240753764325
Tetrahedron,A novel route to a 4-amino steroid: MDL 19687,,10.1016/00404-0399(50)0893h-,1995-07-03,0.6833240753764325
Organic Process Research & Development,Optimization and Scale-up of a Pd-Catalyzed Aromatic C−N Bond Formation: A Key Step in the Synthesis of a Novel 5-HT<sub>1B</sub> Receptor Antagonist,"Searching for the best synthetic route for a given target molecule is a complex task and, by the same token, a key deliverable from a process R&D department. In this vein the challenge for our group was to identify a sustainable manufacturing process for a chiral compound, AR-A2, to be developed for the treatment of certain neurological disorders. Besides designing a method for assembling the core ( R )-2-aminotetralin nucleus, a key feature in the overall synthesis was to provide a robust procedure for creating a new C−N bond between an aromatic ring and a heterocyclic moiety. The methodology employed a Buchwald−Hartwig coupling, and a highly efficient catalytic process was developed using Pd(OAc) 2 as precatalyst, with loadings as low as 0.47 mol % (in laboratory trials one order of magnitude lower) together with ( R )-BINAP as ligand. Optimizing the reaction conditions allowed a virtually quantitative conversion of the brominated aromatic substrate after heating to 110−115 °C in toluene for 4 h. Telescoping this step with a succeeding catalytic hydrogenation to effect an N -debenzylation, followed by precipitation of the benzoate salt offered an overall yield for the two consecutive steps of 88% at 125-kg batch size, combined with excellent stereochemical product purity of 98% ee.",10.1021/op8000146,2008-04-26,0.6833056243910005
Organic Process Research & Development,An Efficient Second-Generation Manufacturing Process for the pan-RAF Inhibitor Belvarafenib,"Herein, the development of a streamlined manufacturing process for the pan-RAF inhibitor belvarafenib (GDC-5573) is reported. The process to belvarafenib features a number of efficient key reactions, including a robust and scalable Pd-catalyzed carbonylation reaction to generate thienopyrimidine 2 and a highly chemoselective Pt/V/C-catalyzed nitro group reduction to access the penultimate intermediate 3 . The final amide coupling was accomplished by a mild and safe protocol employing N,N,N ′,N ′-tetramethylchloroformamidinium hexafluorophosphate as the coupling reagent, which afforded belvarafenib on a multikilogram production scale after recrystallization.",10.1021/acs.oprd.1c00277,2021-09-11,0.6832420051535273
Organic Process Research & Development,"Stereoselective Construction of 3-(Aminoalkylidene)oxindoles in One Pot: Development of a Novel, Robust, and Scalable Process for the Multigram-Scale Preparation of Nintedanib","A palladium-catalyzed novel stereoselective Heck/Buchwald–Hartwig cascade reaction of substituted N -(2-iodophenyl)propiolamides and amines has been established to furnish a series of 3-(aminoalkylidene)oxindole scaffolds with good yields. In addition, we report the development of a robust, scalable, and convergence approach leading to the synthesis of nintedanib ( 1 ). Salient features of the approach include the production of key oxindole intermediate 17 via our advanced Heck/Buchwald–Hartwig reaction cascade, which enables the reduction of the number of synthetic steps. Moreover, our approach avoids the expensive column chromatography purification method for all synthetic steps. Further, we also disclosed an alternative route toward the synthesis of another kinase inhibitor hesperadin ( 2 ) following the above-mentioned cascade method.",10.1021/acs.oprd.3c00469,2024-02-16,0.6832256220561362
Organic Letters,Asymmetric Total Synthesis of (+)-Fostriecin,"[structure: see text] The title compound, a potent protein phosphatase inhibitor and anticancer agent, was prepared by an efficient, multiconvergent asymmetric synthesis. Key transformations include a ring forming olefin metathesis leading to the alpha,beta-unsaturated lactone and creation of the triene moiety via Suzuki cross-coupling.",10.1021/ol025537r,2002-02-20,0.6831659430380321
Synthesis,An Efficient Route to Dipyrrinones: Synthesis of Xanthobilirubic Acid Methyl Ester,"All articles of this category Structually interesting and complicated dipyrrinones, such as xanthobilirubic acid methyl ester (9) , can be synthesized on a large scale from simple, inexpensive starting materials like ethyl acetoacetate, 2,4-pentanedione (1) and ethyl acrylate in 8 steps with an average yield of 80% at each step and an overall 17% yield.",10.1055/s-1990-27094,1990-01-01,0.6831532483885738
Synlett,The Synthesis of (±)-Wilforonide,"All articles of this category The first synthesis of (±)-wilforonide has been completed in ten steps from commercially available starting materials. A high-yielding monomethylation of a reactive ketone enolate, a regioselective α-annulation of an unactivated α-substituted cyclohexanone, and a selective hydrogenation of the resulting unsaturated keto ester were key steps in the synthesis. T. wilfordii extract - wilforonide - regioselective annulation - immunomodulator - anti-inflammatory",10.1055/s-1998-1769,1998-07-01,0.6830653507574238
Organic Letters,Total Synthesis of (−)-Lycoperine A,"Lycoperine A was synthesized through a highly convergent route in which a double alkylation of 2,6-dicyano-N-benzylpiperidine with the octahydroquinoline moiety gave the lycoperine skeleton. The octahydroquinoline was prepared by a desymmetrization reaction of 5-methylcyclohexane-1,3-dione. Hydrolysis, reductive amination, and cyclization gave lycoperine A in 13 steps and 3% overall yield. The absolute configuration of lycoperine A was assigned as 6R,6'R,8R,8'R,13S,17R.",10.1021/ol902389e,2009-11-30,0.6830247649733514
Organic Process Research & Development,"Enabling Synthesis of Triple Reuptake Inhibitor (+)-BMS-820836, a Potential Therapeutic Agent for the Treatment of Depression","Herein, we describe the enabling synthesis of (+)-BMS-820836, a 4,7-disubstituted tetrahydroisoquinoline which was developed as a treatment for a range of neurological diseases, including depression and neurophatic pain. In order to advance the drug candidate into the Phase 1 clinical trials, an efficient and scalable synthesis was required. Three areas of improvement included the development of a regioselective Friedel–Crafts cyclization, a classical resolution for the purification of the desired enantiomer, and a robust Suzuki–Miyaura coupling. These improvements ultimately resulted in the isolation of (+)-BMS-820836 as a free-flowing white solid in 99 area% purity and 3% overall yield after 14 steps.",10.1021/acs.oprd.5b00261,2015-12-22,0.6829648793812321
Synthesis,New Stereoselective Synthesis of Paeonilactone B,A new stereoselective synthesis of paeonilactone B has been achieved in ten steps and in 11.5% overall yield starting from the enantiomerically enriched terpenol 2. Key synthetic steps are based on a regioselective metalation and on a regio- and diastereoselective epoxidation.,10.1055/s-0028-1088039,2009-03-25,0.6829467947050186
Journal of Organic Chemistry,Total Syntheses of Anti-HIV Cyclodepsipeptides Aetheramides A and B,"A concise total synthesis of aetheramide A in an overall yield of 4.7% with a longest linear sequence of 15 steps is described. This synthetic strategy features macrocyclization via an intramolecular trapping of acylketene generated from dioxinone precursor, and stereoselective late-stage methylation of β-ketoamide. Aetheramide B could be synthesized via the ester migration of aetheramide A.",10.1021/acs.joc.6b02292,2016-11-10,0.68289471939003
Organic Process Research & Development,"A Practical and Efficient Synthesis of (3<i>R</i>,4<i>S</i>)-1-Benzyl-4-phenylpyrrolidine-3-carboxylic acid via an Aziridinium Ion Intermediate","A practical and efficient synthesis of (3 R,4 S )-1-benzyl-4-phenylpyrrolidine-3-carboxylic acid ( 1 ), a key chiral building block for synthesis of biologically active compounds was established by utilizing a stereospecific and regioselective chlorination of in situ generated aziridinium ion, followed by a nitrile anion cyclization. Starting from commercially available ( R )-styrene oxide and 3-(benzylamino)propionitrile, the four-step synthesis features a through process without purification of intermediates until isolation of crystalline 1 . The robust, chromatography-free and reproducible synthesis of 1 achieved an 84% overall yield from ( R )-styrene oxide. This highly efficient process was successfully demonstrated at pilot scale with 17 kg output of 1 .",10.1021/op900230r,2009-11-30,0.6828744593231857
Organic Process Research & Development,"Patent Review of Manufacturing Routes to Oncology Drugs: Carfilzomib, Osimertinib, and Venetoclax","Synthetic routes and final forms for three recently approved oncology drugs are reviewed: carfilzomib (Kyprolis), osimertinib (Tagrisso), and venetoclax (Venclexta). Several patent applications have been filed for the major synthetic challenge for carfilzomib, installation of the chiral epoxide. The apparent manufacturing route to osimertinib involves seven steps and a longest linear sequence of six steps with a yield of 56%. The apparent manufacturing route to venetoclax is a ten-step convergent synthesis with a seven-step longest linear sequence that proceeds in 52% yield.",10.1021/acs.oprd.6b00374,2016-12-07,0.6828694425348136
European Journal of Organic Chemistry,Stereoselective Total Synthesis of (+)‐Nephrosteranic Acid and (+)‐Roccellaric Acid through Asymmetric Dihydroxylation and Johnson–Claisen Rearrangement,"Abstract An efficient stereoselective total synthesis of (+)‐nephrosteranic acid and (+)‐roccellaric acid is presented. The synthetic strategy features the regioselective asymmetric dihydroxylation of the γ,δ‐olefinic bond of a α,β,γ,δ‐unsaturated ester and the Johnson–Claisen rearrangement as the key steps. The synthesis is achieved in 10 steps and 6.8 % (nephrosteranic acid) and 7.6 % (roccellaric acid) overall yield.",10.1002/ejoc.201001419,2011-01-10,0.6828666474714207
Organic Letters,The Total Synthesis of Psymberin,"The total synthesis of a new member of the pederin family of natural products, psymberin 1, was accomplished. Using a recently reported novel and efficient PhI(OAc)2 mediated oxidative entry to 2-(N-acylaminal)-substituted tetrahydropyrans as the key step, this total synthesis was executed in a convergent and efficient manner. The longest linear sequence of this synthesis was 22 steps starting from known 6.",10.1021/ol071068n,2007-05-25,0.6828629668896513
Organic Letters,Rapid Total Synthesis of (±)Trigonoliimine A via a Strecker/Houben–Hoesch Sequence,A novel synthetic route to the hexacyclic system of trigonoliimine A was accomplished in four steps from N-phthaloyl 6-OMe-tryptamine. Key reactions include a three-component Strecker-type reaction to fashion the two C-N bonds in the D ring and a subsequent Houben-Hoesch type cyclization to deliver the characteristic seven-membered C ring.,10.1021/ol303344d,2013-01-11,0.6828254993774674
Organic Process Research & Development,"Development of a Scalable Route toward an Alkylated 1,2,4-Triazol, a Key Starting Material for CXCR3 Antagonist ACT-777991","Several synthetic routes toward triazole building block 2-(3-methyl-1 H -1,2,4-triazol-1-yl)acetic acid are described. The main problems of the initial synthetic route via alkylation of 3-Me-1 H -1,2,4-triazole, such as poor regioselectivity, low yield, and purification by column chromatography, could be significantly improved or completely avoided in the second-generation approaches. Key concepts for the design of the alternative synthesis approaches to solve the problem of regioselectivity were the desymmetrization of 3,5-dibromo-1 H -1,2,4-triazole and the de novo synthesis of the triazole core. The scalability of all routes was demonstrated on >100 g scale.",10.1021/acs.oprd.3c00051,2023-04-14,0.6828195261073039
Journal of Organic Chemistry,Formal Total Synthesis of (+)-Gephyrotoxin,"An efficient formal total synthesis of (+)-gephyrotoxin is described. The key step of our strategy relies on the diastereoselective reduction of a chiral pyrrolidine beta-enamino ester obtained by condensation of ( S)-phenylglycinol on a protected 8-hydroxy-3,6-dioxooctanoate.",10.1021/jo801150e,2008-07-19,0.6827932667916967
Synlett,Two Practical Syntheses of a Key Intermediate of 1β-Methylcarbapenem Antibiotics,"All articles of this category Two practical methods for the synthesis of a key intermediate 1 of 1β-methylcarbapenem antibiotics, starting from 4 via readily available olefins 5 and 7 , respectively, are described. 1β-methylcarbapenem key Intermediate - azetidinone carboxylic acid - stereoselective synthesis - potassium permanganate oxidation",10.1055/s-1995-4918,1995-02-01,0.6827704632140411
Synlett,Dimeric Fischer Carbenes: A Bidirectional Dötz Benzannulation and oxa-Pictet-Spengler Strategy for the Synthesis of the Regioisomeric Core of Cardinalin 3,"An efficient, asymmetric synthesis of the regioisomeric dimeric pyranonaphthoquinone core structure of cardinalin 3 is presented. The strategy involves the synthesis of dimeric Fischer carbene, bidirectional Dötz benzannulation, and oxa-Pictet-Spengler reactions as the key steps. The synthesis is achieved in six steps and 7.4% overall yield.",10.1055/s-0030-1258773,2010-09-30,0.6827053336174045
Synthesis,"The Concise Synthesis of a Key Intermediate for the Total Synthesis of Fumagillin, TNP-470, and Ovalicin","The facile synthesis of a key intermediate for the total synthesis of the antiangiogenic compound fumagillin, its semisynthetic analogue TNP-470, and ovalicin is described. The methodology employs a Diels-Alder strategy and a zinc-mediated ring-opening reaction to realize the cyclohexane backbone.",10.1055/s-2008-1067030,2008-04-25,0.6826951447662523
Tetrahedron,"A high yield synthesis of (±)-5,8-dimethoxy-2-α-hydroxyethyl-3,4-dihydronaphthalene, a key intermediate in anthracyclinone synthesis",,10.1016/s0040-4039(01)81954-7,1981-01-01,0.6826876404420797
Organic Letters,Synthesis of Santiagonamine,The first total synthesis of santiagonamine (1) is achieved in 12 steps from isovanillin. A palladium-catalyzed Ullmann cross-coupling reaction and a photocyclization are the key steps in the synthesis.,10.1021/ol0711974,2007-07-21,0.68268063278212
Organic Process Research & Development,Chemical Development of MDL 103371:  An <i>N</i>-Methyl-<scp>d</scp>-Aspartate-Type Glycine Receptor Antagonist for the Treatment of Stroke,"MDL 103371 is a N -methyl- d -aspartate (NMDA)-type glycine receptor antagonist for the potential treatment of stroke. Evaluation of five different synthetic routes, which included Stille, Suzuki, enol ether, Knoevenagel, and the Mukaiyama coupling reactions, revealed the Knoevenagel approach superior for preparing large quantities of drug substance for evaluation. The overall process utilized some classical chemistry. Fischer indole cyclization, followed by a Vilsmeier−Haack formylation and a Knoevenagel condensation gave immediate access into the proper carbon framework of the target molecule. A unique hydrogenation cataylst and solvent system for a nitro reduction, followed by a two step acid−base hydrolysis of a nitrile gave the crude product. Purification was accomplished by a potassium salt crystallization followed by a Schiff base formation to give MDL 103371 in nine steps in an overall yield of 38%.",10.1021/op000286s,2000-09-20,0.6826776532287288
Organic Letters,"Synthetic Approach to Hypoxyxylerone, Novel Inhibitor of Topoisomerase I","[reaction: see text] A potential route to the topoisomerase I inhibitor hypoxyxylerone is demonstrated by a highly convergent synthesis of the penta(O-methyl) derivative. The key step in the approach is an anionic homo-Fries rearrangement, little used to date in natural product synthesis and employed here for the first time with a dinaphthalenic substrate, to access the pentacyclic system of hypoxyxylerone.",10.1021/ol026454d,2002-08-16,0.6826752202472294
Organic Process Research & Development,An Improved and Enantioselective Preparation of the Telaprevir Bicyclic [3.3.0] Proline Intermediate and Reuse of Unwanted Enantiomer,"An improved, concise, and efficient preparation of the telaprevir bicyclic [3.3.0] proline intermediate is presented. The key steps, control points, and the whole process are optimized. The synthesis of racemic intermediate was accomplished in five steps in above 56% overall yield up to 100 g scale with only some simple separations and treatments in the whole process. The new and crucial chiral resolution of the proline intermediate was systematically studied, and the target chiral intermediate was obtained in acceptable yield (30%) and excellent ee value (>99% ee) by a simple washing. The cost of the target chiral intermediate and wastes of the whole process were at least doubly reduced after the effective reuse of the unwanted chiral amino acid by successful decarboxylation.",10.1021/acs.oprd.5b00345,2016-01-05,0.68264382171617
Journal of Organic Chemistry,Total Synthesis of (+)-Isolysergol,"The enantioselective synthesis of (+)-isolysergol was completed in 18 steps, and an overall yield of 11% was obtained from (2 R )-(+)-phenyloxirane as a chiral pool. Key features of the synthesis include a stereoselective intramolecular 1,3-dipolar addition of nitrone with terminal olefin and a Cope elimination to furnish the D ring. A rhodium-catalyzed intramolecular [3 + 2] annulation of a benzene ring with α-imino carbenoid was designed to afford the 3,4-fused indole scaffold at the late stage of the synthesis.",10.1021/acs.joc.3c00614,2023-06-05,0.6826325410515083
Synthesis,Back to the Sugars: A New Enantio and Diastereocontrolled Route to Hexoses from Furfural,"All articles of this category An integrated enantio and diastereocontrolled route to both enantiomers of the eight possible hexoses has been explored starting from furfural, by employing the Sharpless asymmetric dihydroxylation as a key step. At the present, a route to six of the eight possible hexoses has been established. The present synthesis may be taken as a reversion of the sugar-originated furfural to the sugars via a levoglucosenone, a pyrolysate of cellulose, type intermediate. asymmetric dihydroxylation - furfural - hexoses - oxidative ring expansion - enantiocontrolled synthesis",10.1055/s-1999-3382,1999-02-01,0.6826314463129536
Journal of Organic Chemistry,Practical and Efficient Multigram Preparation of a Camphor-Derived Diol for the Enantioselective Lewis Acid Catalyzed Allylboration of Aldehydes,"[reaction: see text] Chiral diols are important molecules with widespread use as chiral auxiliaries and ligands in enantioselective synthesis. Therefore, efficient and practical syntheses of highly dissymmetrical nonracemic diols are still a meaningful pursuit. Two new routes to access camphor-derived chiral diol 1 have been developed. One route employs camphorquinone (3) as the starting material, affording in only two steps the desired diol in 55% overall yield. The second route, from camphor (2), leads to the desired diol in an efficient four-step synthesis, with an overall yield of 55%.",10.1021/jo050207g,2005-04-21,0.682622226894842
Angewandte Chemie International Edition,"Unified, Efficient, and Scalable Synthesis of Halichondrins: Zirconium/Nickel‐Mediated One‐Pot Ketone Synthesis as the Final Coupling Reaction","Unified, efficient, and scalable syntheses of the halichondrin natural products are reported. A newly developed Zr/Ni-mediated one-pot ketone synthesis was used to couple the two halves of the final product at a late stage in the synthesis. With the use of a slight excess of the left halves, the desired ketones were isolated in yields of 80-90 %. The halichondrins were obtained from these ketones in two steps, namely desilylation and [5,5]-spiroketal formation. The new synthetic route was effective for the total synthesis of all members in the homohalichondrin subgroup. The scalability of this process was demonstrated with halichondrin B; 150 mg of halichondrin B (68 % overall yield) were obtained from 200 mg of the right-half precursor.",10.1002/anie.201705523,2017-07-06,0.682605988684688
Journal of Organic Chemistry,Total Synthesis of the Epidermal Growth Factor Inhibitor (−)-Reveromycin B,"The total synthesis of the epidermal growth factor inhibitor reveromycin B (2) in 25 linear steps from chiral methylene pyran 13 is described. The key steps involved an inverse electron demand hetero-Diels-Alder reaction between dienophile 13 and diene 12 to construct the 6,6-spiroketal 11 which upon oxidation with dimethyldioxirane and acid catalyzed rearrangement gave the 5,6-spiroketal aldehyde 9. Lithium acetylide addition followed by oxidation/reduction and protective group manipulation provided the reveromycin B spiroketal core 8 which was converted into the reveromycin A (1) derivative 6 in order to confirm the stereochemistry of the spiroketal segment. Introduction of the C1-C10 side chain began with sequential Wittig reactions to form the C8-C9 and C7-C6 bonds, and a tin mediated asymmetric aldol reaction installed the C4 and C5 stereocenters. The final key steps to the target molecule 2 involved a Stille coupling to introduce the C21-C22 bond, succinoylation, selective deprotection, oxidation, and Wittig condensation to form the final C2-C3 bond. Deprotection was effected by TBAF in DMF to afford reveromycin B (2) in 72% yield.",10.1021/jo001646c,2001-03-03,0.6825311033362856
Journal of Organic Chemistry,New Synthesis for the Monobactam Antibiotic—<b>LYS228</b>,"A new synthesis of LYS228, fitting for further process development for commercial manufacture, is described. The key features of this synthesis include development of new protocols for acylation reactions, application of an asymmetric hydrogenation via dynamic kinetic resolution, and a late-stage ring closure to form β-lactam 1 .",10.1021/acs.joc.9b01916,2020-05-15,0.6824999865338538
Journal of Organic Chemistry,Synthesis of Potent and Orally Efficacious 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitor HSD-016,"Cortisol and the glucocorticoid receptor (GR) signaling pathway has been linked to the development of diabetes and metabolic syndrome. In vivo, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) catalyzes the conversion of inactive cortisone to its active form, cortisol. Existing clinical data have supported 11β-HSD1 as a valid therapeutic target for type 2 diabetes. In our research program, (R)-1,1,1-trifluoro-2-(3-((R)-4-(4-fluoro-2-(trifluoromethyl)phenyl)-2-methylpiperazin-1-ylsulfonyl)phenyl)propan-2-ol (HSD-016) was discovered to be a potent, selective, and efficacious 11β-HSD1 inhibitor and advanced as a clinical candidate. Herein, a reliable and scalable synthesis of HSD-016 is described. Key transformations include an asymmetric synthesis of a chiral tertiary alcohol via Sharpless dihydroxylation, epoxide formation, and subsequent mild reduction. This route ensured multikilogram quantities of HSD-016 necessary for clinical studies.",10.1021/jo200958a,2011-07-07,0.6824985843818934
Organic Letters,Total Synthesis of (+)-Galbulin and Unnatural Lignans,"The total synthesis of (+)-galbulin was achieved in 15% yield and 99% ee over eight steps from commercially available 4-veratraldehyde. The key steps include Meyer's asymmetric tandem addition to a chiral 2-oxazoline-substituted naphthalene, a Pd-catalyzed stereospecific decarboxylative γ-arylation, and a formal anti-Markovnikov hydromethylation. In addition, five unnatural lignans were synthesized using the same synthetic strategy.",10.1021/acs.orglett.0c02294,2020-08-21,0.6824967921574366
Organic Process Research & Development,"Development of a Novel Synthetic Process for 2-Deoxy-3,5-di-<i>O</i>-<i>p</i>-toluoyl-α-<scp>l</scp>-ribofuranosyl Chloride:  A Versatile Intermediate in the Synthesis of 2‘-Deoxy-<scp>l</scp>-ribonucleosides","A novel synthetic route to 2-deoxy-3,5-di- O - p -toluoyl-α- l -ribofuranosyl chloride ( 1 ) from inexpensive d -xylose ( 3 ) is described. 1 is a key intermediate in the synthesis of the antiviral agent 1-(2-deoxy-β- l -ribofuranosyl)thymine (β- l -thymidine) (2) and other 2 ‘-deoxy- l -ribonucleosides. This seven-step synthesis employs a key conversion of the d to the l configuration of the sugar moiety ( 6 to 7 in Scheme 1) using simple reagents and reaction conditions. The entire process involves only three isolation steps. The key compound ( 1 ) was produced in 11% overall yield without chromatography.",10.1021/op0500436,2005-06-10,0.6824863044428834
Tetrahedron,"Synthesis of 1-0-[(3S,4R)-3-hydroxytetrahydrofuran-4-yl]-α-D-glucopyranoside 3,4,3′-trisphosphate as a novel potent IP3 receptor ligand",,10.1016/s0040-4039(98)00954-x,1998-07-01,0.6823782415102243
Organic Process Research & Development,"Practical Synthesis of Triethylammonium (<i>Z</i>)-2-[2-(Boc-amino)thiazol-4-yl]-2-(trityloxyimino)acetate, the Side Chain of Cefmatilen","A practical synthesis of triethylammonium ( Z )-2-[2-( N - tert -butoxycarbonylamino)thiazol-4-yl]-2-(triphenylmethyloxyimino)acetate ( 1 ) which is the C-7 side chain of cefmatilen, a new cephalosporin antibiotic, is described. The conditions were optimized to control the impurity and to increase the yield. Selective acetylation of oxime group before tert -butoxycarbonylation reduced the amount of Boc 2 O. Compound 1 was synthesized from compound 6 by this improved process in 80% overall yield (12% higher than that for the medicinal process) via a four-reaction sequence (95% per reaction).",10.1021/op049804f,2004-12-18,0.6823749500872448
Journal of Organic Chemistry,"Organocatalyzed Protecting-Group-Free Total Synthesis of (<i>S,S</i>)- and (<i>S,R</i>)-Reboxetine, an Antidepressant Drug","An efficient, simple, and concise organocatalyzed protecting-group-free synthetic approach to the stereoisomers of the antidepressant drug reboxetine and its implementation toward the asymmetric synthesis of ( S,S )-reboxetine and ( S,R )-reboxetine from commercially available trans -cinnamaldehyde are described. The synthesis features organocatalytic Jørgensen asymmetric epoxidation, epoxide migration, and Mitsunobu inversion as key steps.",10.1021/acs.joc.2c00886,2022-07-22,0.6823710943575781
Synlett,"Short and Efficient Syntheses of Gabosine I, Streptol, 7-O-Acetylstreptol, 1-epi-Streptol, Gabosine K, and Carba-α-d-glucose from δ-d-Gluconolactone","δ-d-Gluconolactone was carbocyclized into an EOM-protected cyclohexenone in four steps involving perethoxymethylation, phosphonate anion addition, reduction, and oxidation with concomitant Horner-Wadsworth-Emmons alkenation. The stable key enone was efficiently transformed into gabosine I (five steps with 65% overall yield from δ-d-gluconolactone), streptol (six steps, 54% overall yield), 7-O-acetyl-streptol (seven steps, 42% overall yield), 1-epi-streptol (six steps, 49% overall yield), gabosine K (seven steps, 40% overall yield), and carba-α-d-glucopyranose (seven steps, 47% overall yield). The present chemical syntheses, from commercially available δ-d-gluconolactone, provide the highest overall yields of these molecules to date.",10.1055/s-0030-1260547,2011-04-29,0.6823328136980485
Organic Letters,Enantioselective Total Synthesis of the Selective PI3 Kinase Inhibitor Liphagal,"The enantioselective total synthesis of liphagal, a selective inhibitor of PI3K α isolated from the marine sponge Aka coralliphaga, has been achieved. The novel tetracyclic ""liphagane"" skeleton is formed in one step, after the hydrogenation of a dihydroxydrimane phenol benzyl ether in the presence of cationic resin.",10.1021/ol101173w,2010-06-02,0.6823243148812902
Synlett,Total Synthesis of (+)-Cephalosporolide E and (-)-Cephalosporolide F en route to Bassianolone,A stereoselective synthesis of (+)-cephalosporolide E and (-)-cephalosporolide F en route to bassianolone is described.,10.1055/s-0029-1218538,2009-12-01,0.6823112497556941
Tetrahedron,"A general synthetic route towards γ- and δ-lactones. Total asymmetric synthesis of (−)-muricatacin and the mosquito oviposition pheromone (5R,6S)-6-acetoxy-hexadecanolide",,10.1016/s0040-4039(99)00895-3,1999-06-01,0.6823063393275944
Journal of Organic Chemistry,"Asymmetric Synthesis of Telcagepant, a CGRP Receptor Antagonist for the Treatment of Migraine","A highly efficient, asymmetric synthesis of telcagepant (1), a CGRP receptor antagonist for the treatment of migraine, is described. This synthesis features the first application of iminium organocatalysis on an industrial scale. The key to the success of this organocatalytic transformation was the identification of a dual acid cocatalyst system, which allowed striking a balance of the reaction efficiency and product stability effectively. As such, via an iminium species, the necessnary C-6 stereogenicity was practically established in one operation in >95% ee. Furthermore, we enlisted an unprecedented Doebner-Knoevenagel coupling, which was also via an iminium species, to efficiently construct the C3-C4 bond with desired functionality. In order to prepare telcagepant (1) in high quality, a practical new protocol was discovered to suppress the formation of desfluoro impurities formed under hydrogenation conditions to <0.2%. An efficient lactamization facilitated by t-BuCOCl followed by a dynamic epimerization-crystallization resulted in the isolation of caprolactam acetamide with the desired C3 (R) and C6 (S) configuration cleanly. Isolating only three intermediates, the overall yield of this cost-effective synthesis was up to 27%. This environmentally responsible synthesis contains all of the elements required for a manufacturing process and prepares telcagepant (1) with the high quality required for pharmaceutical use.",10.1021/jo101704b,2010-10-18,0.6822554604289994
Organic Letters,An Improved Lanthanum Catalyst System for Asymmetric Amination: Toward a Practical Asymmetric Synthesis of AS-3201 (Ranirestat),"A catalytic asymmetric amination with a lanthanum/amide complex was significantly improved. The use of lanthanum nitrate hydrate in place of lanthanum triisopropoxide made the process reproducible, scalable, and cost-effective. The development of a ternary catalytic system of La/ligand/amine was a key to high ee and catalytic turnover. A 100 g scale reaction was performed to showcase a practical synthesis of a key intermediate for AS-3201, a highly potent aldose reductase inhibitor.",10.1021/ol8008446,2008-06-04,0.6822543152867476
Journal of the American Chemical Society,Highly Efficient Chemical Synthesis of C60: Rational One-Pot Route from Hexachlorocyclopentadiene,,10.1021/ja038144b,2003-12-19,0.6822511720339884
Organic Process Research & Development,"Development of a Scalable Route with Efficient Stereoisomer Control to YZJ-1139, an Orexin Receptor Antagonist","An effort toward the synthesis and process development of the orexin receptor antagonist YZJ-1139( 1 ) was described in this article. YZJ-1139( 1 ) contains the azabicyclic nortropane structure with three chiral centers. By the original process, highly pure intermediates or API could be obtained by chromatography with a relatively low yield. To remove the undesirable stereoisomers as early as possible, intermediate 13 with ( R )-α-phenethyl was synthesized by the Robinson–Schöpf reaction and easily purified as hydrochloride. The single crystal X-ray study was used to confirm the stereo configuration of 13·HCl and 18·HCl . The protecting group could be easily removed by transfer hydrogenation, resulting in enantiomerically pure intermediate 3 as a d -tartarate. The overall yield for preparing YZJ-1139( 1 ) was significantly increased, and this cost-efficient process might be promising in future commercial productions.",10.1021/acs.oprd.1c00457,2022-01-27,0.6822376756030053
Journal of Organic Chemistry,Synthesis of Ceramide Analogues Having the C(4)−C(5) Bond of the Long-Chain Base as Part of an Aromatic or Heteroaromatic System,"Two efficient and stereoselective methods are described for the preparation of aryl and heteroaryl ceramide analogues 2 and 3. The first route involves the addition of an aryllithium or a heteroaryllithium reagent (7a or 25a, respectively) to the L-serine-derived aldehyde 4, followed by hydrolysis of the oxazolidine, liberation of the amino group, and N-acylation. The second route, which was used to prepare arylceramide analogue 2 in eight steps and 28% overall yield starting with 3-bromobenzaldehyde, utilizes a Heck reaction to afford (E)-alpha,beta-unsaturated ester 16, then osmium-catalyzed asymmetric dihydroxylation for the introduction of the desired chirality at C-2 and C-3. Regioselective alpha-azidation of alpha-O-nosyl-beta-hydroxyester 18 with sodium azide, followed by LiAlH(4) reduction of the azido and ester groups and N-acylation, complete the synthesis of arylceramide analogue 2.",10.1021/jo001227f,2000-10-06,0.6822200625045738
Tetrahedron,A simple and efficient synthetic route to benzo[c]phenanthridines,,10.1016/0040-4039(95)01129-6,1995-08-01,0.682205874788349
Tetrahedron,A Simple and Efficient Synthetic Route to Benzo[c]phenanthridines,,10.1016/00404-0399(50)11296-,1995-08-07,0.682205874788349
Tetrahedron,"A new synthetic route to tribenzo[a,e,i][12]annulenes",,10.1016/s0040-4039(99)02346-1,2000-03-01,0.6822003666985403
European Journal of Organic Chemistry,Stereocontrolled Formal Synthesis of Platencin,"A stereocontrolled formal synthesis of platencin was accomplished in 11 steps from a bromophenol derivative, with an overall yield of 13 %. The intermolecular Diels–Alder reaction of masked o ‐benzoquinone and an aldol condensation were the key steps in the construction of the tricyclic core of platencin.",10.1002/ejoc.201800806,2018-07-08,0.6821586538193993
Organic Process Research & Development,Kilogram Synthesis of a Selective Serotonin Reuptake Inhibitor,Process development of a selective serotonin reuptake inhibitor ( 1 ) is described. The synthesis features Nishiyama catalyst-mediated asymmetric cyclopropanation of vinyl indole 2 with ethyldiazoacetate to install the trans- disubstituted cyclopropane. The active pharmaceutical ingredient ( 1 ) was prepared in 13 chemical steps with 9 isolations and proceeded in an overall yield of 34%.,10.1021/op700125z,2008-01-17,0.6820992662062313
Organic Process Research & Development,"A Practical Telescoped Three-Step Sequence for the Preparation of (1<i>R</i>,2<i>R</i>)-2-(4-Bromobenzoyl)cyclohexanecarboxylic Acid: A Key Building Block Used in One of Our Drug Development Projects","A large-scale, robust telescoped process involving acid chloride generation and Friedel–Crafts acylation followed by hydrolysis of an ester was developed for the manufacture of a homochiral disubstituted cyclohexane. Chromatography was avoided, and instead, crystallization was employed to furnish the pure carboxylic acid. This acid was further used as a key building block for the synthesis of drug candidates via amide bond formation using various amines followed by a Suzuki coupling with a pyrazole pinacol ester. The total synthesis of one of the drug candidates on a multihundred gram scale is described.",10.1021/acs.oprd.8b00066,2018-04-27,0.6820722558116696
Tetrahedron,Enantioselective total synthesis of pyrroloquinolone as a potent PDE5 inhibitor,,10.1016/j.tetlet.2008.09.151,2008-10-02,0.6820710394049067
Tetrahedron,A microbial metabolite inhibitor of CD28–CD80 interactions,,10.1016/s0040-4039(02)01029-8,2002-07-01,0.6820628953674334
Tetrahedron,Sulfated liposaccharides inspired by telomerase inhibitor axinelloside A,,10.1016/j.tetlet.2017.11.038,2017-11-20,0.6820628953674334
Tetrahedron,"Oscillapeptin, an Elastase and Chymotrypsin Inhibitor from the Cyanobacterium Oscillatoria agardhii (NIES-204)",,10.1016/00404-0399(50)0980q-,1995-07-17,0.6820628953674334
Tetrahedron,"Oscillapeptin, an elastase and chymotrypsin inhibitor from the cyanobacterium Oscillatoria agardhii (NIES-204)",,10.1016/0040-4039(95)00980-q,1995-07-01,0.6820628953674334
Tetrahedron,"Carteramine A, an inhibitor of neutrophil chemotaxis, from the marine sponge Stylissa carteri",,10.1016/j.tetlet.2007.01.113,2007-01-26,0.6820628953674334
Tetrahedron,"Micropeptin 103, a Chymotrypsin Inhibitor from the Cyanobacterium Microcystis viridis (NIES-103)",,10.1016/s0040-4039(97)00528-5,1997-04-01,0.6820628953674334
Tetrahedron,"Halichlorine, an inhibitor of VCAM-1 induction from the marine sponge Halichondria okadai Kadata",,10.1016/0040-4039(96)00703-4,1996-05-01,0.6820628953674334
Tetrahedron,"Asteropterin, an inhibitor of cathepsin B, from the marine sponge Asteropus simplex",,10.1016/j.tetlet.2008.04.043,2008-04-11,0.6820628953674334
Tetrahedron,On the biosynthesis of an inhibitor of the p53/MDM2 interaction,,10.1016/s0040-4039(01)02239-0,2002-02-01,0.6820628953674334
Tetrahedron,"Sinulamide: an H,K-ATPase inhibitor from a soft coral Sinularia sp.",,10.1016/s0040-4039(98)02438-1,1999-01-01,0.6820628953674334
Synlett,A Practical and Scalable Preparation of Lusianthridin,"Abstract The efficient preparation of the stilbenoid lusianthridin is described. This synthesis relies on a Suzuki–Miyaura coupling and an intramolecular nucleophilic substitution as key reactions to construct the 9,10-dihydrophenanthrene core. The synthesis is completed in seven steps with a 13.2% overall yield, and each step can be conducted on a &gt;20 gram scale. The route has provided 20 grams of lusianthridin for further biological activity studies.",10.1055/a-1828-0352,2022-04-18,0.6820591619234191
Angewandte Chemie International Edition,Gram‐Scale Enantioselective Formal Synthesis of Morphine through an <i>ortho</i>–<i>para</i> Oxidative Phenolic Coupling Strategy,"A gram-scale catalytic enantioselective formal synthesis of morphine is described. The key steps of the synthesis involve an ortho-para oxidative phenolic coupling and a highly diastereoselective ""desymmetrization"" of the resulting cyclohexadienone that generates three of the four morphinan ring junction stereocenters in one step. The stereochemistry is controlled from a single carbinol center installed through catalytic enantioselective hydrogenation. These transformations enabled the preparation of large quantities of key intermediates and could support a practical and scalable synthesis of morphine and related derivatives.",10.1002/anie.201408435,2014-10-06,0.6820575061560508
Journal of the American Chemical Society,"Enantioselective Synthesis of (+)-Cortistatin A, a Potent and Selective Inhibitor of Endothelial Cell Proliferation","This manuscript describes an enantioselective synthesis of the naturally occurring inhibitor of endothelial cell proliferation, cortistatin A. Key steps of the synthesis are a silicate-directed elimination/ring expansion reaction and a highly diastereoselective aza-Prins cyclization with a subsequent transannular etherification.",10.1021/ja8071918,2008-11-19,0.6819874042007931
European Journal of Organic Chemistry,A Concise and Efficient Total Synthesis of Militarinone D,"Abstract A highly stereoselective, concise (14 steps longest linear sequence and 20 steps overall), and efficient (15 % overall yield) synthesis of militarinone D has been accomplished. The key reactions utilized in the sequence are enzymatic desymmetrization, cis / trans isomerization, Horner–Wadsworth–Emmons olefination, and addition of an organolithium species to a highly conjugated chiral aldehyde. The simplicity of the strategy may enable its utilization in the large‐scale production of this target. Moreover, the strategy utilized to design the route should be applicable to the preparation of analogs that bear a variety of substituted pyridinone core structures.",10.1002/ejoc.201500380,2015-05-15,0.6819333567282122
European Journal of Organic Chemistry,Asymmetric Synthesis of (+)- and (–)-Streptenol A,"The asymmetric synthesis of (+)-streptenol A was carried out in ten steps and with high enantioselectivity (ee ≥ 96%). The key steps are the α-alkylation of 2,2-dimethyl-1,3-dioxan-5-one RAMP hydrazone A (1), subsequent deoxygenation and elaboration of the side chain via aldehyde B to furnish (+)-streptenol A in 23% overall yield. In analogy, the enantiomer (–)-streptenol A was synthesized using the corresponding SAMP hydrazone in 18% overall yield.",10.1002/(sici)1099-0690(199904)1999:4<751::aid-ejoc751>3.0.co;2-r,1999-04-01,0.6819277902685539
Organic Letters,Protecting-Group-Free Total Synthesis of (−)-Lycopodine via Phosphoric Acid Promoted Alkyne Aza-Prins Cyclization,"A protecting-group-free route for the total synthesis of (-)-lycopodine was demonstrated in only 8 steps from Wade's fawcettimine enone (12 steps from commercial availiable (R)-(+)-pulegone). The key core of this alkaloid was constructed through a phosphoric acid promoted and highly stereocontrolled alkyne aza-Prins cyclization reaction, synchronously establishing the bridged B-ring and the C13 quaternary stereocenter. Importantly, the synthesis further features a new efficient approach for the preparation of other lycopodine-type alkaloids.",10.1021/acs.orglett.6b02072,2016-08-16,0.681910944338274
Angewandte Chemie International Edition,"A Symmetry‐Based Concise Formal Synthesis of Platencin, a Novel Lead against “Superbugs”","Quick access: A concise and efficient formal synthesis of platencin has been accomplished in nine steps from a commercially available starting material. The synthesis utilized only one protecting group. The base-catalyzed Michael cyclization of precursor 1 afforded the key diketone 2, which was converted into the desired core structure 4 via the radical intermediate 3.",10.1002/anie.200902338,2009-07-01,0.6819083994679288
Organic Process Research & Development,A Practical and Scalable Method for Manufacturing JAK Inhibitor ASP3627,"ASP3627 ( 1 ) is a potent Janus kinase inhibitor discovered and developed by Astellas Pharma Inc. Here, we report the development of a practical and scalable method for manufacturing ASP3627 featuring a six-reaction telescoping process consisting of DIBAL reduction, hydrolysis, Wittig reaction, cyclization, and a two-step sequence to remove the SEM group. In addition, a simple palladium removal procedure using l -cysteine is described. This method was used to successfully perform the first multikilogram synthesis of ASP3627, producing 30 kg with high purity in excellent overall yield.",10.1021/acs.oprd.9b00269,2019-09-09,0.6818548187686356
Tetrahedron,Novel route in the synthesis of ψ[CH2NH] amide bond surrogate,,10.1016/j.tetlet.2007.11.112,2007-11-26,0.6818519862735892
Organic Letters,Collective Total Synthesis of (−)-Lundurines A–C,"A collective asymmetric total synthesis of lundurines A–C using l -pyroglutamic acid derived from the chiral pool is described. The key steps include a tandem reductive amination/lactamization sequence to introduce the pyrrolidinone ring, a palladium-catalyzed intramolecular direct C–H vinylation of indole to construct the crucial polyhydroazocine ring, and a Lewis acid promoted formal [3 + 2] cycloaddition/N 2 extrusion process to install the polysubstituted cyclopropyl ring.",10.1021/acs.orglett.8b00210,2018-03-08,0.6818326172246265
Organic Letters,A Highly Efficient Synthesis of Potent and Selective Butyrolactam Inhibitors of 11β-Hsd1,A convergent synthesis of structurally novel butyrolactam 11beta-HSD1 inhibitors is described. The approach features an efficient Ireland-Claisen reaction to construct a highly substituted aldehyde building block which is converted to a lactam via a tandem reductive amination/cyclization sequence. The generality of the synthetic sequence is demonstrated during the preparation of two additional potent 11beta-HSD1 inhibitors.,10.1021/ol061429j,2006-08-01,0.681829040530736
Journal of Organic Chemistry,"Enantioselective Synthesis of (+)-(2<i>R</i>,3<i>S</i>,6<i>R</i>)-Decarestrictine L","A convergent enantioselective synthesis of (+)-(2 R,3 S,6 R )-decarestrictine L ( 1), a natural inhibitor of cholesterol biosynthesis, is described from commercially available ( S )-malic acid and ( R )-isobutyl lactate. The third chiral center was created by stereoselective reduction of a chiral α-hydroxy ketone, and an intramolecular S N 2-type reaction allowed the stereocontrolled formation of the tetrahydropyranyl ring.",10.1021/jo972187r,1998-03-19,0.68176448394061
Synthesis,Improved Synthesis of an Ascaroside Pheromone Controlling Dauer Larva Development in Caenorhabditis elegans,"Using an efficient Wacker oxidation as a key step, we describe a significantly improved synthesis of the dauer-promoting ascaroside 2 for biological studies of the novel sterol ring methylase STRM-1.",10.1055/s-0029-1216967,2009-08-21,0.6817530694124703
Organic Process Research & Development,Preparation of the HIV Attachment Inhibitor BMS-663068. Part 1. Evolution of Enabling Strategies,"The development of two enabling routes that led to the production of >1000 kg of BMS-663068 ( 3 ) is described. The route identified for the initial 100 kg delivery to support development activities and initial clinical trials involved the conversion of 2-amino-4-picoline to the parent active pharmaceutical ingredient (API), followed by pro-drug installation and deprotection. To eliminate the problematic isolation of the parent API and synthesis of di- t -butyl(chloromethyl)phosphate, a second-generation pro-drug installation route was developed which involved the conversion of a late-stage common intermediate to an N(1)-thioether derivative followed by chloromethylation, displacement with di- t -butylpotassium phosphate, and deprotection. This second strategy resulted in the multikilogram scale preparation of the API in 14 linear steps and ∼7% overall yield.",10.1021/acs.oprd.7b00134,2017-08-09,0.6817362602031989
Tetrahedron,"L-755,805, a new polyketide endothelin binding inhibitor from an actinomycete",,10.1016/0040-4039(95)00215-x,1995-03-01,0.6817327515898998
Tetrahedron,Polyhydroxylated aziridinylcyclopentanes as glycomimetics: a new competitive inhibitor of α-mannosidase,,10.1016/s0040-4039(01)01343-0,2001-09-01,0.6817327515898998
Journal of the American Chemical Society,"Asymmetric Total Synthesis of (−)-Azaspirene, a Novel Angiogenesis Inhibitor","The asymmetric total synthesis of (-)-azaspirene, an angiogenesis inhibitor, has been accomplished, establishing its absolute stereochemistry. The key steps are a MgBr2.OEt2-mediated, diastereoselective Mukaiyama aldol reaction, a NaH-promoted, intramolecular cyclization of an alkynylamide, and the aldol reaction of a ketone containing functionalized gamma-lactam moiety without protection of tert-alcohol and amide functionalities.",10.1021/ja0276826,2002-09-18,0.6817256324378341
Chemical Science,A robust and scalable synthesis of the potent neuroprotective agent (−)-huperzine A,"(−)-Huperzine A (1) is a tricyclic alkaloid that is produced in low yield by the Chinese herb Huperzia serrata. There is intense contemporary interest in clinical application of (−)-huperzine A (1) for treating neurodegenerative diseases and protecting against the lethal effects of chemical warfare agents, such as sarin and VX. We report a robust, scalable, and efficient synthesis of (−)-huperzine A (1) from (R)-4-methyl-cyclohex-2-ene-1-one (5). Our route proceeds in 35–45% overall yield, delivers (−)-huperzine A (1) in only eight steps from cyclohexenone 5, requires only three chromatographic purifications, and can provide gram quantities of the target. This route represents a critical, enabling advance toward detailed evaluation of (−)-huperzine A (1) in clinical settings.",10.1039/c1sc00455g,2011-01-01,0.6817221353102636
Journal of Organic Chemistry,Enantioselective Synthesis of Cuparane Sesquiterpenes. Synthesis of (−)-Cuparene and (−)-δ-Cuparenol,"(−)-Cuparene and (−)-δ-cuparenol, two cuparane-type sesquiterpenoids, were synthesized from β-cyclogeraniol in 47% and 27% overall yield, respectively, using a Katsuki−Sharpless asymmetric epoxidation, a pinacollic rearrangement, and a Robinson annulation as key synthetic steps.",10.1021/jo960463g,1996-01-01,0.6817088627932818
Journal of Organic Chemistry,Flexible and Convergent Total Synthesis of Cyclotheonamide B,"A convergent approach using two key intermediates, segment A [a l -proline- l -α-hydroxy-β-homoarginine- d -phenylalanine (Pro-hArg- d -Phe) tripeptide] and segment B [a vinylogous l -tyrosine- l -2,3-diaminopropanoic acid (vTyr-Dpr) dipeptide], was developed for the synthesis of cyclotheonamide B (Scheme 1). The starting compound for the preparation of the hArg moiety 7, the predominant part of segment A, was N α -(benzyloxycarbonyl)- N ω, N ω ‘-bis( tert -butyloxycarbonyl)-l-arginine methyl ester ( 15, Scheme 2), which was converted into the aldehyde 16 and subsequently homologated using [tris(methylthio)methyl]lithium as a carboxylic acid anion equivalent. Coupling with properly protected Pro and d -Phe derivatives gave smoothly the desired Pro-hArg- d -Phe tripeptide derivative 24 . The key feature of segment B, i.e., the l -tyrosine-derived α,β-unsaturated γ-amino acid 4, was prepared by a Wadsworth−Emmons olefination of the aldehyde 29 (Scheme 3) derived from N -( tert -butyloxycarbonyl), O - tert -butyl- l -tyrosine methyl ester ( 28 ). Selective N -( tert -butyloxycarbonyl) removal in the presence of the aryl tert -butyl ether present in the fully protected segment B, i.e., 32, was achieved by treatment with trimethylsilyl triflate/2,6-lutidine to give vTyr-Dpr dipeptide derivative 34 in quantitative yield. Coupling of the key intermediates 24 and 34 using 2-(1 H -benzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TBTU) afforded the protected linear pentapeptide 35 in high yield (Scheme 4). Treatment of 35 with Pd(PPh 3 ) 4 /morpholine resulted in simultaneous removal of the C -terminal allyl group and the N -terminal allyloxycarbonyl group to yield 36 . Ring closure was effected under dilution conditions by treatment with TBTU/1-hydroxybenzotriazole/4-(dimethylamino)pyridine and gave the protected cyclopentapeptide 37 in 61% yield. Oxidation of the hydroxyl group with Dess−Martin periodinane (24 h, 40 °C) in the presence of tert -butyl alcohol gave 38, which was then subjected to O,N -deprotection with trifluoroacetic acid/thioanisole. Subsequent HPLC purification afforded cyclotheonamide B in an overall yield of 1.8% in 17 steps.",10.1021/jo961447m,1997-06-13,0.6816881212802639
Organic Letters,"Total Synthesis of Chloptosin, a Potent Apoptosis-Inducing Cyclopeptide","A bidirectional total synthesis of chloptosin has been achieved in 16 operations (32 individual reactions) and 3% overall yield from the readily available materials. Palladium-catalyzed tryptophan synthesis, diastereoselective selenocyclization and oxidative deselenation successfully served as key steps in construction of the dimeric core amino acid. 2-Bromo-1-ethyl pyridinium tetrafluoroborate was efficiently employed in the peptide couplings with spatial encumbrance in this synthesis.",10.1021/ol100135a,2010-02-05,0.6816815633254155
Journal of the American Chemical Society,Multigram Synthesis of the C29−C51 Subunit and Completion of the Total Synthesis of Altohyrtin C (Spongistatin 2),"A multigram synthesis of the C29-C51 subunit of altohyrtin C (spongistatin 2) has been accomplished. Union of this intermediate with the C1-C28 fragment and further elaboration furnished the natural product. Completion of the C29-C51 subunit began with the aldol coupling of the boron enolate derived from methyl ketone 8 and aldehyde 9. Acid-catalyzed deprotection/cyclization of the resulting diastereomeric mixture of addition products was conducted in a single operation to afford the E-ring of altohyrtin C. The diastereomer obtained through cyclization of the unwanted aldol product was subjected to an oxidation/reduction sequence to rectify the C35 stereocenter. The C45-C48 segment of the eventual triene side chain was introduced by addition of a functionalized Grignard reagent derived from (R)-glycidol to a C44 aldehyde. Palladium-mediated deoxygenation of the resulting allylic alcohol was followed by adjustment of protecting groups to provide reactivity suitable for the later stages of the synthesis. The diene functionality comprising the remainder of the C44-C51 side chain was constructed by addition of an allylzinc reagent to the unmasked C48 aldehyde and subsequent dehydration of the resulting alcohol. Completion of the synthesis of the C29-C51 subunit was achieved through conversion of the protected C29 alcohol into a primary iodide. The synthesis of the C29-C51 iodide required 44 steps with a longest linear sequence of 33 steps. From commercially available tri-O-acetyl-d-glucal, the overall yield was 6.8%, and 2 g of the iodide was prepared. The C29-C51 primary iodide was amenable to phosphonium salt formation, and the ensuing Wittig coupling with a C1-C28 intermediate provided a fully functionalized, protected seco-acid. Selective deprotection of the required silicon groups afforded an intermediate appropriate for macrolactonization, and, finally, global deprotection furnished altohyrtin C (spongistatin 2). This synthetic approach required 113 steps with a longest linear sequence of 37 steps starting from either tri-O-acetyl-d-glucal or (S)-malic acid.",10.1021/ja030317+,2003-09-27,0.6816788823470582
European Journal of Organic Chemistry,"Synthesis of Enantiopure 6,11‐Methylene Lipoxin B<sub>4</sub> Methyl Ester","Abstract The synthesis of Lipoxin B 4 analogs (LXB 4 ) to gain access to stabilized inflammation resolving compounds is an actual field of research. Focusing on variation and stabilization of the conjugated E,Z,E,E C6–C13 tetraene moiety of natural LXB 4 , a methylene bridge introduced between C6 and C11 suppresses any Z/E isomerization of the C8–C9 olefin. Intending to enable prospective structure variations in connection with the C1–C5 and C14–C20 fragments, a convergent total synthesis has been developed. Optically active C1–C12 building blocks were build‐up from cycloheptatriene 1‐carbonester (C6–C11, C21) and glutaryl chloride (C1–C5) using Friedel‐Crafts‐type acylation and chiral HPLC. The C13–C20 segment had been generated via a five‐step sequence starting from heptanoyl chloride. Horner key olefination enabled the assembly of the carbon backbone. A final five‐step sequence including a chelate Cram reduction of the unsaturated ketone moiety afforded the target 6,11‐methylene LXB 4 methyl ester.",10.1002/ejoc.202001591,2021-01-19,0.6816770472202718
Journal of Organic Chemistry,"Carbodiimide-Mediated Preparation of the Tricyclic Pyrido[3‘,2‘:4,5]pyrrolo[1,2-<i>c</i>]pyrimidine Ring System and Its Application to the Synthesis of the Potent Antitumoral Marine Alkaloid Variolin B and Analog","A total synthesis of the marine alkaloid variolin B has been completed in 13 steps in an overall yield of 6.5% from 3-formyl-4-methoxypyridine. Our approach is based on the sequential formation of the 7-azaindole ring, the tricyclic pyrido[3',2':4,5]pyrrolo[1,2-c]pyrimidine ring system, and finally installation of the 2-aminopyrimidine ring at C5. The required 7-azaindole ring appropriately substituted is formed by a modified indole synthesis involving a nitrene insertion process (two steps). Formation of the annelated pyrimidine ring is achieved by two routes both involving a carbodiimide-mediated cyclization process, which allow incorporation of the amine functionality at C9 of the core tricyclic (six steps). Installation of the northeast 2-aminopyrimidine ring at C5 is performed using the Bredereck protocol (three steps). Ultimate, thermal decarboxylation with concomitant O-methyl deprotection and further N-benzyl deprotection by the action of triflic acid completed the synthesis of the target natural product variolin B.",10.1021/jo026508x,2002-12-05,0.6816475875287065
Journal of the American Chemical Society,Total Synthesis of (±)-Cylindrospermopsin,"The first total synthesis of the novel hepatotoxin (±)-cylindrospermopson ( 1 ) has been accomplished in 20 steps from 4-methoxy-3-methylpyridine ( 12 ) in 3.5% overall yield. The substituted piperidine A ring 19 was generated stereospecifically by a four-step sequence using the addition of trimethylsilylethynylmagnesium bromide to 12 to give 16 and stereospecific addition of vinylcuprate to 16 to form 17 . The reaction of diamine 26 with cyanogen bromide produced the cyclic guanidine C ring of 27 . The key step in the synthesis was bromination of ketone 31, followed by hydrogenation to liberate the free guanidine, which underwent an intramolecular S N 2 reaction to form the tetrahydropyrimidine ring B of 32 . Further hydrogenation reduced the ketone to yield 42% of 32 containing the fully functionalized tricyclic system and protected hydroxymethyluracil side chain of cylindrospermopsin. Hydrolysis of the pyrimidine in concentrated hydrochloric acid and selective monosulfation completed the synthesis of cylindrospermopsin.",10.1021/ja000647j,2000-05-01,0.6816321011434454
Synlett,"Efficient and Scalable Synthesisof 3,5,7-Trisubstituted 1<i>H</i>-Indazolesas Potent IKK2 Inhibitors","Efficient and scalable chemical approaches to 3,5,7-trisubstituted 1H-indazoles were developed and applied to the synthesis of 1,1-dimethylethyl 4-[7-(aminocarbonyl)-5-bromo-1H-indazol-3-yl]-1-piperidinecarboxylate, a key intermediate for 3,5,7-trisubstituted 1H-indazole, which was identified as a potent IKK2 inhibitor. The sequence allows for a scalable preparation of the target compound in eight steps and proceeds in 40% overall yield from readily available starting material.",10.1055/s-0028-1087364,2008-11-24,0.6816046311281656
Organic Process Research & Development,The Manufacture of a Homochiral 4-Silyloxycyclopentenone Intermediate for the Synthesis of Prostaglandin Analogues,"A process is described for the synthesis of kilogram quantities of homochiral 4-silyloxycyclopentenone ( R )- 1, a key intermediate useful for the synthesis of a plurality of prostaglandin analogue drugs. Cyclopentenone ( R )- 1 was synthesized in 14 isolated steps from furfural. Key steps in the synthesis include a Wittig reaction, Piancatelli rearrangement, and an enzymatic resolution featuring in situ recycling of the undesired enantiomer furnishing the desired homochiral alcohol in ≥99.5% ee. As a retort to the unsatisfactory coformation of about 8% at best of the trans -olefin in the Wittig reaction, a change to the order of several steps and the identification of a recrystallisable, amine salt derivative, 2, allowed the unwanted isomer to be controlled to as low as 0.2%.",10.1021/op300188x,2012-11-15,0.6816012884237826
Organic Process Research & Development,Pilot Scale Synthesis of a Novel Nonpeptide Angiotensin II Receptor Antagonist,"FR143187 is a novel nonpeptide angiotensin II receptor antagonist under development at Fujisawa Pharmaceutical Co. for the treatment of hypertension. Development of a process for preparation on a large scale is described. The optimized process is 10 steps in length and uses only commercially available materials for each step. Efficient methylation of the 2-position of a pyrrole derivative was achieved by reduction of a Mannich base via the quaternary ammonium salt. Selective cyanation directed by a solvent effect was also investigated. Process improvement efforts focused on optimized reaction conditions for each step, leading to a high-quality product according to a new and concise synthetic route.",10.1021/op9800055,1998-04-30,0.6815452529674217
Organic Process Research & Development,"Efficient Synthesis of (2<i>S</i>,3<i>S</i>)-2-Ethyl-3-methylvaleramide Using (1<i>S</i>,2<i>S</i>)-Pseudoephedrine as a Chiral Auxiliary","An efficient and scaleable synthesis of (2 S,3 S )-2-ethyl-3-methylvaleramide ( 1 ) has been developed starting from inexpensive and readily available l -isoleucine. The key step in this process is an asymmetric alkylation using (1 S,2 S )-pseudoephedrine as a chiral auxiliary. A practical procedure was developed to remove the sterically hindered pseudoephedrine auxiliary from the amide. The process consists of eight chemical steps and five isolations without any chromatographic purification. It has been successfully implemented to prepare several multikilogram batches of the target compound 1 in 41% overall yield.",10.1021/op800260j,2009-01-30,0.6814199639182974
Journal of Organic Chemistry,"Efficient Synthesis of Achiral <i>s</i><i>eco</i>-Cyclopropylbenz[2,3-<i>e</i>]indoline Analogues:  [4-Amino-2-(5,6,7-trimethoxyindole-2-carboxamido)naphthalen-1-yl]ethyl Chloride and [4-Hydroxy-2-(5,6,7-trimethoxyindole-2-carboxamido)naphthalen-1-yl]ethyl Chloride","Achiral seco-aminocyclopropylbenz[2,3-e]indoline and seco-hydroxycyclopropylbenz[2,3-e]indoline (seco-CBI) analogues of the duocarmycins and CC-1065, e.g., 7 and 8, are potent anticancer agents. This paper describes significantly improved synthetic strategies for preparing these compounds. Starting from Martius acid (9), the new strategy gave a 13-fold increase in the overall yield of 7, and the use of di-tert-butyl malonate was economically beneficial. For compound 8, the new strategy employed an Emmons-Horner reaction, followed by a Stobbe condensation, and the overall yield was improved 15-fold.",10.1021/jo060501o,2006-05-16,0.6814151639541408
Synthesis,"An Improved Synthesis of Methyl 2-O-Benzoyl-4,6-O-benzylidene-α-D-altropyranoside",,10.1055/s-1972-21836,1972-01-01,0.6813822245824511
Synthesis,"An Improved Synthesis of Methyl 4,6-<i>O</i>-Benzylidene-2,3-dideoxy-α-D-<i>erythro</i>-hex-2-enopyranoside",,10.1055/s-1980-28919,1980-01-01,0.6813822245824511
Journal of Organic Chemistry,A Short and Efficient Synthesis of the Pharmacological Research Tool GW501516 for the Peroxisome Proliferator-Activated Receptor δ,The most potent and selective peroxisome proliferator-activated receptor delta (PPARdelta) agonist GW501516 (1) was synthesized in 4 steps and 78% overall yield starting from o-cresol by using a one-pot regiocontrolled dialkylation of mercaptophenol 5 as the key step.,10.1021/jo035140g,2003-10-10,0.6813790819454636
Journal of the American Chemical Society,"Studies toward the Unique Pederin Family Member Psymberin: Full Structure Elucidation, Two Alternative Total Syntheses, and Analogs","Two synthetic approaches to psymberin have been accomplished. A highly convergent first generation synthesis led to the complete stereochemical assignment and demonstrated that psymberin and irciniastatin A are identical compounds. This synthesis featured a diastereoselective aldol coupling between the aryl fragment and a central tetrahydropyran core and a novel one-pot procedure to convert an amide, via intermediacy of a sensitive methyl imidate, to the N-acyl aminal reminiscent of psymberin. The highlights of the second generation synthesis include an efficient iridium-catalyzed enantioselective bisallylation of neopentyl glycol and a stepwise Sonogashira coupling/cycloisomerization/reduction sequence to construct the dihydroisocoumarin unit. The two synthetic avenues were achieved in 17-18 steps (longest linear sequence, ~14-15 isolations) from 3 fragments prepared in 7-8 (first generation) and 3-8 (second generation) steps each. This convergent approach allowed for the preparation of sufficient amounts of psymberin (~ 0.5 g) for follow-up biological studies. Meanwhile, our highly flexible strategy enabled the design and synthesis of multiple analogs, including a psymberin-pederin hybrid, termed psympederin, that proved crucial to a comprehensive understanding of the chemical biology of psymberin and related compounds that will be described in a subsequent manuscript.",10.1021/ja3057612,2012-09-24,0.6813581653620633
Synthesis,A Short Enantioselective Synthesis of the Topoisomerase II Inhibitor (+)-Eleutherin,A Hauser-Kraus annulation was used as a key step for the concise enantioselective synthesis of the topoisomerase II inhibitor (+)-eleutherin. © Georg Thieme Verlag Stuttgart.,10.1055/s-2007-983841,2007-08-27,0.6813465904122801
Organic Process Research & Development,Development of a Scalable Electrophilic Amination Protocol for the Multi-kg Production of 5-Methyl-2-pyridinesulfonamide: A Regulatory Starting Material of Endothelin Receptor Antagonist Clazosentan,"5-Methyl-2-pyridinesulfonamide is a regulatory starting material of endothelin receptor antagonist clazosentan. The original route to the key sulfonamide relied on the textbook conversion of the corresponding thiophenol to the intermediate sulfonyl chloride followed by its quenching with aqueous ammonia. However, this route suffered from a wide range of issues such as a low overall yield (29%), challenging aqueous workups and isolations, and the formation of a genotoxic benzyl chloride impurity. Therefore, we developed a conceptually novel production route for 5-methyl-2-pyridinesulfonamide. The new process relied on selectively oxidizing the thiophenol to the intermediate sulfinate salt followed by an electrophilic amination of the nucleophilic sulfinate sulfur-atom with hydroxylamine- O -sulfonic acid (HOSA). This oxidation/electrophilic amination sequence worked as a “one-pot” procedure by simply adding HOSA to the reaction mixture after complete oxidation of the thiophenol with 70% aq. t -BuOOH. The process was extensively optimized with regard to the oxidation step, increasing the stability of HOSA in the reaction mixture, and the final isolation of 5-methyl-2-pyridinesulfonamide. The new process was performed on a 22 kg scale, delivering the desired product as a white solid in 69% overall yield and excellent purity (>99.9% a/a).",10.1021/acs.oprd.3c00131,2023-06-23,0.6813345445581191
Journal of the American Chemical Society,Total Synthesis of the Antiviral Glycolipid Cycloviracin B<sub>1</sub>,"The first total synthesis of the antiviral agent cycloviracin B1 (1) is described which provisionally establishes the hitherto unknown configuration of the chiral centers on the lateral fatty acid chains as (3R,19S,25R,3'R,17'S,23'R). Key steps en route to this glycolipid include a highly efficient template-directed macrodilactonization step for the formation of the lactide core followed by a two-directional synthesis strategy for the completion of the fatty acid annexes. The latter comprises a modified Julia-Kocienski olefination carried out in the presence of the base-labile beta-hydroxyester moieties of the macrodiolide, as well as a titanium-catalyzed asymmetric addition of the dialkylzinc reagent 11 controlled by cyclohexane-1,2-diamine bistriflate 12 for the formation of the chiral center at C-17' which is selectively glycosylated by taking recourse to the trichloroacetimidate method.",10.1021/ja027346p,2002-08-10,0.6812510245436632
Synthesis,Enantiospecific Synthesis of a Chiral Intermediate in Steroid Synthesis,"All articles of this category An enantiospecific route to a potentially useful intermediate 13 in the intramolecular Diels-Alder route to steroids is described. The key step involves efficient ring cleavage of 9,10-dibromocamphor (7) to provide a monocyclic bromoester 8 of defined chirality. This is readily transformed to 13 .",10.1055/s-1989-27434,1989-01-01,0.6811728552631463
Reaction Chemistry & Engineering,A new reaction route for the synthesis of 2-methyl-5-ethylpyridine,"In this work, a novel synthesis route to produce 2-methyl-5-ethylpyridine (MEP) from the cyclic acetaldehyde ammonia trimer (AAT) is explored.",10.1039/c7re00100b,2017-01-01,0.6811060364013913
Organic Letters,Highly Enantioselective Total Synthesis of (+)-Isonitramine,"A new efficient enantioselective synthetic method of (+)-isonitramine is reported. (+)-Isonitramine was obtained in 12 steps (98% ee and 43% overall yield) from δ-valerolactam via enantioselective phase-transfer catalytic alkylation, Dieckman condensation, and diastereoselective reduction as key steps.",10.1021/ol2033042,2012-01-17,0.681099151250294
Journal of Organic Chemistry,"Total Synthesis of (+)-Lycoricidine and Conduramine B-1, <i>ent</i>-C-1, C-4, D-1, <i>ent</i>-F-1, and <i>ent</i>-F-4, and Formal Synthesis of (−)-Laminitol: a <i>C</i><sub>2</sub>-Symmetric Chiral-Pool-Based Flexible Strategy","A facile and diversity-oriented synthetic strategy toward aminocyclitol natural products from inexpensive C 2 -symmetric l -tartaric acid was developed. The pivotal epoxide was used as a common intermediate to accomplish eight diverse target molecules in six to eleven steps. Various allyl-amine-type conduramines were synthesized in a diastereoselective manner. Heck arylation was explored to construct a phenanthridone ring in a concise synthesis of (+)-lycoricidine. In addition, a highly efficient formal synthesis of (−)-laminitol was developed.",10.1021/acs.joc.9b01221,2019-07-23,0.6810952132756958
Synthesis,"A Stereoselective Synthesis of (4<i>E</i>,7<i>S</i>)-(-)-7-Methoxydodec-4-enoic Acid","A stereoselective synthesis of (4E,7S)-(-)-7-methoxy dodec-4-enoic acid has been accomplished in eight steps from hex: anal in 24% overall yield. The key steps involved the catalytic asymmetric allylation of hexanal and the coupling reaction of a chiral alkyne and a protected bromide in the presence of t-BuLi.",10.1055/s-2005-918516,2006-01-01,0.681083596610012
Organic Process Research & Development,"Practical Synthesis of 6-Amino-1-hydroxy-2,1-benzoxaborolane: A Key Intermediate of DNDI-6148","Visceral leishmaniasis (VL), a parasitic, poverty-linked, neglected disease, is endemic across multiple regions of the world and fatal if untreated. There is an urgent need for a better and more affordable treatment for VL. DNDI-6148 is a promising drug candidate being evaluated for the treatment of VL; however, the current process for producing the key intermediate of DNDI-6148, 6-amino-1-hydroxy-2,1-benzoxaborolane, is expensive and difficult to scale up. Herein, we describe two practical approaches to synthesizing 6-amino-1-hydroxy-2,1-benzoxaborolane from inexpensive and readily available raw materials. Starting with 4-tolunitrile, the first approach is a five-step sequence involving a Hofmann rearrangement, resulting in an overall yield of 40%. The second approach utilizes 2-methyl-5-nitroaniline as the starting material and features borylation of aniline and continuous flow hydrogenation as the key steps, with an overall yield of 46%. Both routes bypass the nitration of 1-hydroxy-2,1-benzoxaborolane, which is challenging and expensive to scale. In particular, the second approach is more practical and scalable because of the mild operating conditions and facile isolation process.",10.1021/acs.oprd.4c00031,2024-03-29,0.6810812635915507
Journal of the American Chemical Society,"Total Synthesis of Gypsetin, Deoxybrevianamide E, Brevianamide E, and Tryprostatin B:  Novel Constructions of 2,3-Disubstituted Indoles","A concise and efficient total synthesis of the acyl-CoA:cholesterol acyltransferase inhibitor gypsetin ( 1 ) is described. The route features a straightforward method for the introduction of a reverse prenyl group into the C2-position of an N -phthaloyl-protected tryptophan ( 11 ). The total synthesis of gypsetin was completed by the dimethyldioxirane-promoted double-oxidative cyclization of a prefashioned diketopiperazine ( 19 ). Total syntheses of deoxybrevianamide E ( 24 ) and brevianamide E ( 25 ) following similar procedures are also described. The reaction of nucleophiles with in situ-generated 3-chloroindolenines provides a route to 2,3-disubstituted indoles from 3-substituted precursors. Indications of the scope and limitations of such reactions are provided. A total synthesis of tryprostatin B ( 41 ), a diketopiperazine derived from an l -tryptophan derivative (bearing a prenyl group at the α position of the indole) and l -proline, was accomplished. The key step involved the introduction of the prenyl function onto a protected tryptophan congener ( 11 ). A route for the prenylation of ketones with virtually no competitive reverse prenylation is also provided.",10.1021/ja9925249,1999-12-01,0.6810702062977821
Organic Process Research & Development,Multi-Kiloscale Enantioselective Synthesis of a Vitronectin Receptor Antagonist,"The development of a novel, cost-effective synthesis of the vitronectin receptor antagonist SB-273005 became necessary as the compound proceeded to Phase 1. A practical synthesis of the compound presented challenges to the process chemist. Chief among the challenges was developing an enantioselective route to the compound. Second was either developing a scalable Mitsunobu coupling of the side chain to the main body or finding alternate chemistry. In this paper we will describe the chemistry we developed which allowed us to make over a hundred kilograms of SB-273005 by a process that we believe is suitable for even larger scale manufacturing.",10.1021/op0499021,2004-08-17,0.6809776568280734
Journal of Organic Chemistry,Practical Asymmetric Synthesis of a Potent Cathepsin K Inhibitor. Efficient Palladium Removal Following Suzuki Coupling,"A large-scale, chromatography-free synthesis of a potent and selective Cathepsin K inhibitor 1 is reported. The key asymmetric center was installed by addition of (R)-pantolactone to the in situ-generated ketene 4a. The final step of the convergent synthesis of 1 was completed via Suzuki coupling of aryl bromide 7a with unprotected aryl piperazine boronic acid 13. Residual palladium and iron generated in the Suzuki coupling were efficiently removed from crude 1 via a simple extractive workup using lactic acid.",10.1021/jo0205614,2003-03-04,0.6809732159978689
Organic Process Research & Development,Route Design and Development of Tetrachlorantraniliprole: Copper-Catalyzed Cyclization and One-Pot Preparation of Pyrazole Acid Chloride,"Synthetic strategies for preparing insecticide tetrachlorantraniliprole ( 1 ) were explored. Target compound 1 was synthesized from 2,3,5-trichloropyridine ( 2 ) using a six-step process. The obtained yield of 51.7% was considerably higher than the 4.7% yield of the initial seven-step process. Process highlights include copper-catalyzed cyclization of 3-chloro-2-hydrazinopyridine ( 3 ) for forming the key intermediate 2-(3,5-dichloropyridin-2-yl)-5-oxopyrazolidine-3-carboxylate ( 4 ), one-pot preparation of pyrazole acid chloride ( 9 ) from thionyl chloride, and a coupling reaction of pyrazole acid chloride ( 9 ) with benzamide ( 10 ) to afford target compound 1 without an acid scavenger. The process represents a reliable alternative for large-scale manufacturing of tetrachlorantraniliprole ( 1 ).",10.1021/acs.oprd.2c00141,2022-11-18,0.6809624803326769
Organic Process Research & Development,"Process Research and Large-Scale Synthesis of a Novel 5,6-Dihydro-(9H)-pyrazolo[3,4-<i>c</i>]-1,2,4-triazolo[4,3-<i>a</i>]pyridine PDE-IV Inhibitor","An efficient synthesis of the PDE IV inhibitor, 9H-cyclopentyl-7-ethyl-3-(thiophen-2-yl)-pyrazolo[3,4- c ]-1,2,4-triazolo-5,6-dihydro-[4,3- a ]pyridine 1 is described. Starting from commercially available γ-caprolactone, the synthesis was carried out in 10 steps. Key transformations were the selective O-methylation of diketone, 3-hydroxy-1-(4-methoxybenzyl)-4-propionyl-5,6-dihydro-1H-pyridin-2-one, with dimethyl sulfate and cesium carbonate in dimethylformamide, a one-pot pyrazole formation with subsequent acidic deprotection to provide lactam, 1-cyclopentyl-3-ethyl-1,4,5,6-tetrahydropyrazolo[3,4- c ]pyridin-7-one, and finally the utilization of imidate, 1-cyclopentyl-7-ethoxy-3-ethyl-4,5-dihydro-1H-pyrazolo[3,4- c ]pyridine for the introduction of the triazole moiety. This process avoided the use of harsh reaction conditions, undesirable reagents and overcame the environmental concerns in the original synthesis.",10.1021/op010222x,2001-09-25,0.6809295955325607
Organic Letters,Total Synthesis of the Tetrasubstituted Furan Fatty Acid Metabolite CeDFP via Au-Catalyzed Intermolecular Alkyne Hydroarylation,"The first total synthesis of the tetrasubstituted furan fatty acid (FFA) metabolite 5-[(1 E )-2-carboxyethenyl]-3,4-dimethyl-2-furanpentanoic acid (CeDFP) is reported. CeDFP is a FFA metabolite isolated from shark livers and is related to the known FFA metabolites CMPF and CMPentylF. Key elements of the synthetic route to CeDFP include an iodine-promoted 5- endo - dig cyclization of a 1,2-alkyne diol, a methyllithium-mediated insertion of the C 3 -methyl group, and a Au(I)-catalyzed intermolecular hydroarylation to introduce the unsaturated ester.",10.1021/acs.orglett.9b01786,2019-06-12,0.6808816443991688
Tetrahedron,A novel and efficient route to chiral 2-substituted carbocyclic 5′-N-ethyl-carboxamido-adenosine (C-NECA),,10.1016/s0040-4039(01)93795-5,1989-01-01,0.6808231371117947
Journal of Organic Chemistry,Practical Enantioselective Synthesis of Endothelin Antagonist S-1255 by Dynamic Resolution of 4-Methoxychromene-3-carboxylic Acid Intermediate,"A practical multikilogram-scale synthesis of enantiomerically pure S-1255 (1), a potent and orally active ET(A) receptor antagonist, is described. Utilizing readily available starting materials and reagents, the entire sequence of reactions starting from 2,5-dihydroxyacetophenone 8 proceeded under mild conditions to give 1 in an excellent chemical yield (8 steps, 41% overall yield) and in a high enantiopurity (98% ee). The crucial step of the synthesis is a dynamic resolution of key intermediate 16. (R)-Methoxy acid (R)-16 having 97-99% ee was obtained in 83-84% yield from racemic 16 as a crystalline (1S,2R)-(+)-norephedrine or (+)-cinchonine salt by the dynamic resolution comprising concurrent crystallization and in situ racemization. A mechanism of the dynamic resolution through a ring-opened zwitterionic intermediate is discussed. In the final synthetic step, an effective carbon-carbon bond formation between the C4 carbon and the p-anisyl group was accomplished by a conjugate addition-elimination reaction of Grignard reagent 3 to (R)-16 to give 1 having 98% ee. Owing to high efficiencies of functional group transformations, carbon-carbon bond formations, and the dynamic resolution, the synthesis required no chromatographic purification and was amenable to a multikilogram-scale preparation. Several kilograms of 1 for clinical trials were successfully prepared by this process.",10.1021/jo0261092,2002-10-09,0.6807516909572353
Organic Letters,"Enabling Synthesis of ABBV-2222, A CFTR Corrector for the Treatment of Cystic Fibrosis","An enabling preclinical synthetic route to cystic fibrosis candidate ABBV-2222 is described. Two stereoselective steps provide access to an aminochroman intermediate with excellent control, and a late-stage demethylation/difluoromethylation sequence provides efficient access to the target molecule.",10.1021/acs.orglett.9b02099,2019-07-01,0.6807221236044132
Synthesis,"Synthesis of 3-Diethylamino-1-ethylisothiazolo[3,4-<i>b</i>]pyridinium Perchlorate and an Improved Route to 3-Azaisatoic Anhydride",,10.1055/s-1982-30029,2002-05-15,0.6807085222101141
Organic Letters,Enantioselective Synthesis of Pladienolide B and Truncated Analogues as New Anticancer Agents,"An enantioselective synthesis of natural anticancer macrolide pladienolide B is described. The synthetic highlights include Sharpless asymmetric epoxidation, ring closing metathesis (RCM), Ireland-Claisen rearrangement, Shi epoxidation, and Pd-catalyzed Stille coupling as key steps. The synthetic route also allowed the synthesis of the truncated analogues (41a-d) of pladienolide B.",10.1021/ol401458d,2013-07-03,0.6806904473217291
Synthesis,Kilogram Synthesis of Crebinostat,"A kilogram-scale synthetic route to crebinostat, a small molecule inhibitor of histone deacetylases (HDACs), is developed successfully. Starting from pimelic acid, dimethyl pimelate is obtained in high yield via methyl esterification. The latter is ammoniated by hydrazine and hydroxylamine successively to give the key intermediate 7-hydrazinyl- N -hydroxy-7-oxoheptanamide, which is coupled with 4-biphenylcarboxaldehyde in ethanol to give crebinostat in 37% yield over four steps. The final product with 99.5% total purity (HPLC) contains E / Z -isomers in a ratio of around 1.3:1, which is confirmed by 1 H NMR spectroscopy. Purification methods of the intermediates and the final product involved in the route are given, which make this process environmentally friendly, cost-effective, and feasible for scale-up operation.",10.1055/s-0035-1561917,2016-03-11,0.6806264042862011
Journal of Organic Chemistry,Total Synthesis and Glycosidase Inhibition of Broussonetine I and J<sub>2</sub>,"The first total synthesis of both broussonetine I and J2 together with their enantiomers have been accomplished via the same synthetic route through 18 and 16 steps in excellent overall yields (18% and 19%, respectively), starting from R-glyceraldehyde. Broussonetine I was found to be a potent inhibitor of β-glucosidase (IC50 = 2.9 μM), while ent-broussonetine I and ent-broussonetine J2 were found to be potent inhibitors of α-glucosidase (IC50 = 0.33 and 0.53 μM, respectively).",10.1021/jo4010553,2013-07-06,0.6806165392931466
Organic Process Research & Development,"A Practical Asymmetric Synthesis of the Antiviral Agent Lobucavir, BMS-180194","A practical synthesis of the antiviral agent lobucavir, [1 R -(1α,2β,3α)]-2-amino-9-[2,3-bis(hydroxymethyl)cyclobutyl]-6 H -purin-6-one (BMS-180194), is described. The key chiral intermediate, [1 S -(1α,2β,3α)]-3-hydroxy-1,2-cyclobutanedimethanol, dibenzoate ester, was made by an asymmetric [2 + 2] cycloaddition of dimenthyl fumarate with ketene dimethyl acetal followed by sequential diester reduction, benzoylation, deketalization, and stereoselective ketone reduction. Regioselective N9-alkylation of the tetra- n -butylammonium salt of 2-amino-6-iodopurine with the derived cyclobutyltriflate furnished the purinecyclobutyl dibenzoate. Methanolysis followed by acid hydrolysis produced lobucavir in a 35% overall yield with an ee > 99%.",10.1021/op970214+,1998-10-07,0.6805996889253302
Organic Process Research & Development,Development of a Kilogram-Scale Route for Clinical Sample Production of the Intravenous Anesthetic Cipepofol,"Propofol has been widely used as a clinical anesthetic for a few decades. Its derivative with a three-membered ring, Cipepofol, was found to be equally effective and with less side effects. Here, we report a process for the scale-up total synthesis of Cipepofol . It could be obtained in five steps from the commercially available 2-isopropylphenol. The key reactions involved Claisen rearrangement, Simmons–Smith cyclopropanation, and chiral resolution through carbamate formation/crystallization, followed by hydrolysis and wiped-film distillation. The reaction conditions were mild, and the involved reagents were easily accessible. With this process, the final product was synthesized in a 14% overall yield, without column chromatographic purification. The synthetic route offered a shorter, robust, and economical production of Cipepofol (chemical purity > 99.5%, 99.5% ee) in kg scale.",10.1021/acs.oprd.1c00306,2022-02-22,0.6805235621721324
European Journal of Organic Chemistry,Total Synthesis of Spiroalkaloids Lycibarbarines A–C,"Abstract The concise and efficient synthesis of tetrahydroquinoline alkaloids lycibarbarines A−C has been accomplished in four steps from a common intermediate derived from commercially available 2‐deoxy‐ D ‐ribose and 8‐hydroxyquinoline. For the synthesis of the unique tetracyclic spiro‐heterocycle skeleton we employed a synthetic strategy that features two key transformations: iodomethyllithium‐based homologation of lactone / N‐alkylation to access tetracyclic spiro‐heterocycle skeleton in one step and one‐pot acetonide deprotection, hemiacetal formation, and spirocyclization cascade process.",10.1002/ejoc.202300518,2023-07-06,0.680477493801634
Organic Process Research & Development,Practical Synthesis of Oxepanoprolines,"A new, more scalable route for the synthesis of the common oxepanoproline southern fragment of the antibiotic candidates iboxamycin, cresomycin, and BT-33 is presented. A key transformation in the route is a diastereoselective TiCl 4 -mediated conjugate addition of an allylsilane to an Evans N -acryloyloxazolidinone, followed by syn -aldol addition of the resultant titanium enolate to ( R )-Garner’s aldehyde, which assembles all the stereocenters within the target molecule in a single operation.",10.1021/acs.oprd.4c00521,2025-02-19,0.680429497295848
Organic Process Research & Development,A Scaleable Synthesis of Dutasteride: A Selective 5α-Reductase Inhibitor,"An improved and scaleable process for Dutasteride ( 1 ), a synthetic 4-azasteroid derivative essentially used for the treatment of prostate diseases, is described.",10.1021/op700068g,2007-08-18,0.6804235464250991
Journal of Organic Chemistry,Asymmetric Total Synthesis of Meptazinol,"The first enantioselective synthesis of ( S )-meptazinol in 14 steps from commercially available ethyl 4-oxo-3,4-dihydropyridine-1(2 H )-carboxylate, being widely used in racemic form for pain treatment, and, en route, the formal synthesis of two anti-Alzheimer’s agents are reported. A novel ring expansion of 2-azabicyclo[4.1.0]heptanes, readily available via the stereoselective cyclopropanation of 1,2,3,4-tetrahydropyridine-4-ols, provides an effective entry to 3,3-disubstituted azepanes that represent the core for a variety of approved drugs.",10.1021/acs.joc.2c00272,2022-04-12,0.6804062096257051
Synlett,Facile Route for Novel Quinazolinone-Fused Azauracils through Cyclodesulfurization of Thioquinazolinones,"An efficient, novel, short, and high-yielding one-pot protocol for the synthesis of diverse quinazolinone-fused azauracil heterocycles through cyclodesulfurization and intramolecular cyclization of thioquinazolinone using silver cyanate is described.",10.1055/s-0030-1259301,2011-01-01,0.6803971187017781
Organic Letters,Total Synthesis of (−)-Hennoxazole A,"An enantioselective, convergent, total synthesis of the antiviral marine natural product (-)-hennoxazole A has been completed in 17 steps, longest linear sequence, from serine methyl ester and in 9 steps from an achiral bisoxazole intermediate. Elaboration of a thiazolidinethione allowed for rapid assembly of the pyran-based ring system. Key late-stage coupling was effected by deprotonation of the bisoxazole methyl group, followed by alkylation with an allylic bromide side chain segment. [structure: see text]",10.1021/ol070244p,2007-02-23,0.6803949842841445
Organic Process Research & Development,Development of a Practical Synthetic Route of a PDE V Inhibitor KF31327,"An efficient route suitable for a large-scale preparation of KF31327 ( 1 ), a potent phosphodiesterase V inhibitor, has been developed. We selected 7-chloro-2,4(1 H,3 H )-quinazolinedione ( 15 ) as a starting material, which gave the desired 6-nitro compound with good selectivity. In the chlorination of 7-ethylamino-6-nitro-2,4(1 H,3 H )-quinazolinedione ( 17 ), reaction conditions were optimized to minimize the amount of phosphorus oxychloride, and 2,4-dichloro-7-ethylamino-6-nitroquinazoline ( 14 ) was obtained in excellent yield. After the selective substitution at C4 position, the chloro substituent at C2 position was successfully removed by hydrogenation concomitant with the reduction of nitro group. The construction of the imidazothione ring was achieved by using phenyl isothiocyanate as a thiocarbonyl donor instead of extremely flammable carbon disulfide. Multikilograms of drug substance have been successfully prepared by these procedures.",10.1021/op010025y,2001-06-28,0.680382881922042
Synthesis,A Short Asymmetric Synthesis of Sauropunols A–D,"A short and efficient asymmetric synthesis of natural sauropunols A, B, and C/D has been accomplished in 6 steps from divinylcarbinol with overall yield of 19%, 7% and 32%, respectively. The key synthetic steps include effective Sharpless asymmetric epoxidation of penta-1,4-dien-3-ol and a highly diastereoselective Pd-catalysed oxycarbonylation of pentene-1,2,3-triol. The structures of sauropunols A and B have been confirmed.",10.1055/s-0036-1588999,2017-04-18,0.6803562881412629
Tetrahedron,"A new route to the olivacine type alkaloid ring system via the fischer base intermediate. A simple synthesis of 6H-pyrido-[4,3-b]-carbazole",,10.1016/s0040-4039(01)85973-6,1979-01-01,0.6802808737734736
Journal of the American Chemical Society,The Total Synthesis of (+)-Tedanolide,"The first total synthesis of the (+)-tedanolide is described. Pivotal steps are the Felkin-selective aldol coupling between C12 and C13 and an efficient Mitsunobu macrolactonization. Selective protecting group transformations and subsequent oxidations generate the macrocyclic triketone. In the endgame of the synthesis, four TBS groups are removed in one reaction and a chemo- and stereoselective final step epoxidation generates (+)-tedanolide.",10.1021/ja0659572,2006-10-06,0.6802775796405568
Tetrahedron,An efficient synthesis of biaryls via noncatalysed anionic coupling of an arylsodium with haloarenes,,10.1016/j.tetlet.2004.10.123,2004-11-12,0.6802555020746706
Synthesis,Palladium-Catalyzed Ring Opening of Isoprene Monoxide with Nitrogen Nucleophiles - Asymmetric Synthesis of Branched Amino Sugars,"The Pd-catalyzed regio- and enantioselective ring opening of isoprene monoxide with primary amines as pronucleophiles is developed with good yield and enantioselectivity, constructing a quaternary stereocenter enantioselectively. This methodology was used as the chirality inducing key step in the asymmetric synthesis of vancosamine derivative 19. The synthesis was achieved in 9 total steps and 28.6% overall yield.",10.1055/s-2005-918443,2005-01-01,0.680228276284383
Journal of the American Chemical Society,A Concise Synthesis of Berkelic Acid Inspired by Combining the Natural Products Spicifernin and Pulvilloric Acid,"We describe a concise synthesis of the structurally novel fungal extremophile metabolite berkelic acid, an effort leading to an unambiguous assignment of C22 stereochemistry. Our synthetic approach was inspired by the recognition that berkelic acid displays structural characteristics reminiscent of two other fungal metabolites, spicifernin and pulvilloric acid. Based on this notion, we executed a synthesis that features a Ag-catalyzed cascade dearomatization-cycloisomerization-cycloaddition sequence to couple two natural product inspired fragments. Notably, a spicifernin-like synthon was prepared with defined C22 stereochemistry in seven steps and three purifications (24-28% overall yield). A potentially useful anti-selective conjugate propargylation reaction was developed to introduce the vicinal stereodiad. An enantioconvergent synthesis of the other coupling partner, the aromatic precursor to pulvilloric acid methyl ester, was achieved in eight steps and 48% overall yield. The total synthesis of berkelic acid and its C22 epimer was thus completed in a 10 step linear sequence and 11-27% overall yield.",10.1021/ja905387r,2009-07-24,0.6801597295383539
Organic Process Research & Development,An Efficient and Cost-Effective Synthesis of 2-Phenyl-3-aminopyridine,"The synthesis of 2-phenyl-3-aminopyridine, a key intermediate in the preparation of 2-phenyl-3-aminopiperidine, from 2-chloro-3-aminopyridine is described using an imine as a protecting group for an aminopyridine. The in situ protection of 2-chloro-3-aminopyridine with benzaldehyde followed by Suzuki coupling with phenylboronic acid and subsequent acid hydrolysis provided the titled compound in a single, high-yielding step from inexpensive and commercially available starting materials.",10.1021/op000227e,2001-02-07,0.6801580769785408
Organic Letters,An Expedient Protecting-Group-Free Total Synthesis of (±)-Dievodiamine,"The first total synthesis of the Evodia rutaecarpa derived natural product dievodiamine is described. The convergent synthesis was performed without protecting groups, delivering a route that is short and high yielding and uses limited chromatography. Key steps include organometallic addition into a DHED adduct and the Stille coupling of two advanced intermediates to complete the synthesis.",10.1021/ol4013469,2013-06-20,0.6801517027927695
Organic Process Research & Development,Robust Synthesis of Methyl 5-Chloro-4-fluoro-1<i>H</i>-indole-2-carboxylate: A Key Intermediate in the Preparation of an HIV NNRTI Candidate,"A synthetic preparation of methyl 5-chloro-4-fluoro-1 H -indole-2-carboxylate, a key intermediate towards phosphoindole inhibitors of HIV non-nucleoside reverse transcriptase, is described. The five-step synthesis involved Boc protection of the commercially available 4-chloro-3-fluoroaniline and regioselective iodination at C-2. After facile Boc deprotection, cyclization of the resultant o -iodoaniline gave the corresponding 5-chloro-4-fluoro-indole-2-carboxylic acid which was subsequently esterified to provide the target indole ester in 56% overall yield. Identification of 6-chloro-7-iodo-2(3 H )-benzoxazolone as a significant side product in the iodination step led to the development of conditions which eliminated its formation in subsequent batches. Advantages of this alternative approach relative to existing methodologies include (1) potentially hazardous diazonium and azido species were not required, (2) regioisomeric products were not generated, and (3) chromatographic isolations were avoided, as all intermediates were easily crystallized. As a result, the key indole ester was produced rapidly at 100-fold increased scale compared to previous reports with a 10-fold improvement in overall yield.",10.1021/op1001808,2010-08-16,0.6801362240253606
Organic Process Research & Development,Synthesis of Fingolimod Employing Regioselective Aziridine Ring-Opening Reaction as a Key Step,"An efficient and scalable synthesis of the immunomodulating drug fingolimod hydrochloride has been developed with the aziridine regioselective ring-opening reaction as a key step. This manuscript describes design, detailed synthetic route scouting, and optimization study of the aziridine ring-opening reaction. As a starting material for the polar part of the fingolimod molecule, cheap, common, and widely commercially available tris(hydroxymethyl)aminomethane was used. n -Octyl group was introduced into the molecule either via Kumada or Negishi cross-couplings, or alternatively by Sonogashira cross-coupling followed by hydrogenation. The final step consists of a one-pot acidic deprotection both of the acetonide and Boc group, providing thus highly pure fingolimod hydrochloride from the crude reaction mixture directly. The described process is highly effective, is industrially applicable, and has been successfully applied to 500 g scales of the target product.",10.1021/acs.oprd.1c00248,2021-09-03,0.6801070087393039
Journal of Organic Chemistry,<i>N</i>-Isopropylsulfinylimines as Useful Intermediates in the Synthesis of Chiral Amines:  Expeditive Asymmetric Synthesis of the Calcimimetic (+)-NPS R-568,"An efficient and high-yielding approach for the asymmetric synthesis of calcimimetic (+)-NPS R-568 (1) has been developed. The key step of the synthesis is the highly diastereoselective addition of methyl Grignard to the (SS,E)-N-(3-methoxybenzylidene)-2-propanesulfinamide [5(S)], which afforded a single diastereoisomer in high yield in short reaction time.",10.1021/jo7018703,2007-12-23,0.6800981328603154
Tetrahedron,Asymmetric synthesis of (+)-pilosinine: a formal synthesis of (+)-pilocarpine,,10.1016/s0040-4039(00)92211-1,1992-04-01,0.6800558592080399
Tetrahedron,Asymmetric synthesis. XXXII. Formal synthesis of (-) - Perhydrohistrionicotoxin.,,10.1016/s0040-4039(00)74361-9,1991-11-01,0.6800558592080399
Synthesis,Asymmetric Synthesis of (-)-6<i>-epi</i>-Centrolobine,"A stereoselective total synthesis of (-)-6-epi-centro­lobine, an unnatural analogue of (-)-centrolobine, starting from readily available tri-O-acetyl-d-glucal has been described for the first time. The key steps involved in this synthetic approach are stereoselective C-glycosidation, dehydroxylation and Wittig reaction. The target molecule was achieved in nine steps with 49% overall yield.",10.1055/s-2008-1067218,2008-08-06,0.6800211707986558
Organic Letters,"Synthesis of a B Ring Opened 7,8-<i>seco</i>-Vitamin B<sub>12</sub> Derivative with Grob Fragmentation","A synthetic route toward B ring opened 7,8-seco-cyanocobalamins is described. Hydrolysis of a novel c-lactone vitamin B12 (B12) derivative generates a cobalamin (Cbl) with a β-bromo alcoholate subunit that reacts in situ via Grob fragmentation to the secocorrin.",10.1021/ol401572j,2013-08-30,0.6800116349070139
Tetrahedron,"An efficient synthesis of 2-(1-methyl-1,2,5,6-tetrahydropyridin-3-yl)morpholine: a potent M1 selective muscarinic agonist",,10.1016/j.tetlet.2007.04.135,2007-05-02,0.6799473228270216
Organic Process Research & Development,Practical Asymmetric Synthesis of a Calcitonin Gene-Related Peptide (CGRP) Receptor Antagonist Ubrogepant,"The development of a scalable asymmetric route to a new calcitonin gene-related peptide (CGRP) receptor antagonist is described. The synthesis of the two key fragments was redefined, and the intermediates were accessed through novel chemistry. Chiral lactam 2 was prepared by an enzyme mediated dynamic kinetic transamination which simultaneously set two stereocenters. Enzyme evolution resulted in an optimized transaminase providing the desired configuration in >60:1 syn / anti . The final chiral center was set via a crystallization induced diastereomeric transformation. The asymmetric spirocyclization to form the second fragment, chiral spiro acid intermediate 3, was catalyzed by a novel doubly quaternized phase transfer catalyst and provided optically pure material on isolation. With the two fragments in hand, development of their final union by amide bond formation and subsequent direct isolation is described. The described chemistry has been used to deliver over 100 kg of our desired target, ubrogepant.",10.1021/acs.oprd.7b00293,2017-10-19,0.6799136773125338
Organic Letters,"Asymmetric Total Synthesis of (2<i>R</i>)-Hydroxynorneomajucin, a Norsesquiterpene from <i>Illicium jiadifengpi</i>","We report the first total synthesis of (2 R )-hydroxynorneomajucin, a norsesquiterpene derived from the Illicium genus. This natural product displays neurotrophic properties. Small molecule neurotrophins have potential as therapeutics in neurodegenerative diseases. Key steps of our synthesis include a Tsuji–Trost reaction, a Pauson–Khand cyclization, and a Nagata hydrocyanation. A simple sequence of reductions and a Mukaiyama hydration introduce the A-ring substituents with the correct configurations. The overall synthesis was completed in 17 steps (longest linear sequence, LLS).",10.1021/acs.orglett.2c01207,2022-05-02,0.6799129092555121
Organic Letters,Divergent Total Synthesis of Taiwaniaquinones A and F and Taiwaniaquinols B and D,"A divergent approach was developed toward the total synthesis of taiwaniaquinoids. An advanced intermediate 5a with trans A/B ring junction was concisely assembled by employing a Bi(OTf)3-catalyzed cationic cyclization and a Wolff-type ring contraction as key steps. This common intermediate was readily converted to racemic taiwaniaquinones A and F and taiwaniaquinols B and D, respectively.",10.1021/ol400717h,2013-04-11,0.6798952408779465
Organic Process Research & Development,Practical Synthesis of a Stable Precursor for Positron Emission Tomography Imaging Agent <sup>18</sup>F-GTP1,"18 F-GTP1 is a deuterated small molecule positron emission tomography (PET) imaging agent used to visualize tau tangles in Alzheimer’s disease patients. The first-generation synthesis of 18 F-GTP1 ’s nonradiolabeled alkyl tosylate precursor was plagued by low-yielding steps, inefficient chromatographic purifications, and variable product quality. Due to these limitations, a more robust second-generation route was developed and successfully executed on kilogram scale. A reduction with LiAlD 4 incorporated geminal deuterium atoms, while an efficient amidation reaction accessed the key acrylamide coupling partner. Moreover, the tricyclic imidazo[1,2- a ]pyrimidine core was assembled via a novel, convergent, and highly selective phosphoramidate-directed annulation. The improved synthesis eliminated all chromatography en route to a high-yielding and reproducible acid-promoted tosylation as the final step.",10.1021/acs.oprd.0c00301,2020-07-28,0.6798834108981348
Organic Process Research & Development,"Development of a Scalable Synthetic Route to BMS-986251, Part 2: Synthesis of the Tricyclic Core and the API","BMS-986251, a potent and efficacious RORγt inverse agonist, was synthesized starting from 6-iodotetralone using 13 chemical transformations with only eight isolated intermediates. The synthesis involved a four-step telescoped diastereoselective aza-Michael reaction-annulation sequence followed by installation of the heptafluoro- iso -propyl side chain and final amidation to furnish the desired API.",10.1021/acs.oprd.1c00125,2021-06-15,0.6798819738677326
Organic Process Research & Development,"A Rapid, Large-Scale Synthesis of a Potent Cholecystokinin (CCK) 1R Receptor Agonist","The development of a scalable synthesis of a potent cholecystokinin (CCK) 1R receptor agonist is described. The focus on a rapid short-term delivery rather than longer-term development allowed for the preparation of multihundred gram quantities to support aggressive timelines and evaluate safety and pharmacological studies. Key improvements involved streamlining the preparation of imidazole acid 7 and discovery of a more efficient preparation of naphthyl piperazine fragment 23, including an improved preparation of 3-bromonaphthallic anhydride 16 .",10.1021/op800176e,2008-10-28,0.6798709099578448
Tetrahedron,An improved synthesis of a novel α1A partial agonist including a new two-step synthesis of 4-fluoropyrazole,,10.1016/j.tetlet.2010.03.080,2010-03-26,0.6798445184488487
Synlett,Chemistry of Imino Glycals: Preparation and Application to the Synthesis of (+)-Fagomine,All articles of this category The synthesis of imino glucal 2 from tri- O -benzyl-d-glucal in 8 steps is described. This novel imino sugar building block is further converted into (+)-fagomine by a two-step hydrogenation sequence. carbohydrates - piperidines - stereoselective synthesis - imino glycals - (+)-fagomine,10.1055/s-2001-16039,2001-01-01,0.6798170524544039
Angewandte Chemie International Edition,Total Synthesis of Actinorhodin,"The enantioselective total synthesis of actinorhodin (1) is described. The synthesis features 1) dual benzyne reactions en route to the monomer, 2) the trans-selective installation of the side chain, and 3) a regioselective oxidative dimerization.",10.1002/anie.201814172,2019-01-28,0.6797531571530764
Organic Process Research & Development,Efficient Multikilogram Synthesis of a VLA-4 Antagonist via a Povarov Reaction,"Herein we describe the practical synthesis of a novel VLA-4 antagonist 1 as a potential treatment for multiple sclerosis. The key step is based on the Povarov reaction of an imine with an alkene to access a tetrahydroquinoline intermediate, leading to the corresponding quinoline core after an oxidative aromatization step. The development of the synthesis of 1 led to decreased complexity and the elimination of chromatographic purifications. These improvements were demonstrated at scale by the production of 32 kg of 1 in high yield with excellent purity.",10.1021/acs.oprd.9b00421,2019-11-27,0.6796846597369832
Journal of Organic Chemistry,Protecting-Group-Free Total Synthesis of (±)-Subincanadine F,"With chemoselective Dieckmann condensation as the key step, the protective-group-free total synthesis of (+/-)-subincanadine F was accomplished in 7 steps from the commercially available tryptamine in 33% overall yield.",10.1021/jo901444e,2009-09-04,0.6796784832732359
Organic Process Research & Development,Total Synthesis of Entecavir: A Robust Route for Pilot Production,"A practical synthetic route for pilot production of entecavir is described. It is safe, robust, and scalable to kilogram scale. Starting from ( S )-(+)-carvone, this synthetic route consists of a series of highly efficient reactions including a Favorskii rearrangement-elimination-epimerization sequence to establish the cyclopentene skeleton, the Baeyer–Villiger oxidation/rearrangement to afford the correct configuration of the secondary alcohol, and a directed homoallylic epoxidation followed by epoxide ring-opening to introduce the hydroxyl group suitable for the Mitsunobu reaction. In addition, the synthesis contains only four brief chromatographic purifications.",10.1021/acs.oprd.8b00007,2018-02-12,0.6796040380997542
Journal of Organic Chemistry,Enantioselective Synthesis of Nelfinavir via Asymmetric Bromocyclization of Bisallylic Amide,"We describe a concise enantioselective synthesis of the HIV-protease inhibitor nelfinavir (1) via a new route in which the key step is construction of the central optically active 1,2-amino alcohol framework via asymmetric bromocyclization of bisallylic amide with N-bromosuccinimide in the presence of a catalytic amount of ( S)-BINAP or ( S)-BINAP monoxide. The remaining alkene and bromo functionalities were used to install the requisite thioether and chiral perhydroisoquinoline units, respectively.",10.1021/acs.joc.8b00039,2018-02-26,0.6795869126747589
Journal of Organic Chemistry,Convergent Total Synthesis of Exochelin 772SM,"A convergent total synthesis of the natural mycobacterial iron chelator desferri-exochelin 772SM (D-EXO) is described. The synthetic procedure proceeds in 11 steps in the longest linear sequence, with an overall yield of 8.6%. The described procedure uses cheap starting materials and requires a limited number of chromatographic purifications. The concise strategy divides the exochelin into five key building blocks, allowing easy alternation of each single building block. Herein, the presented synthetic strategy is well suited to facilitate the synthesis of analogues and medicinal chemistry development efforts in a time- and resource-efficient manner.",10.1021/acs.joc.3c00561,2023-06-09,0.6795793728093008
Synthesis,"Regioselective Synthesis of Dihydrofuro[3,2-<i>g</i>]coumarin-6-one","New regioselective routes for the preparation of dihydrofuro[3,2-g]coumarin-6-one (5) have been studied. An efficient three-step synthesis of methyl 3-(5′-chloroacetyl-2′,4′-dihydroxy­phenyl)propanoate (7) from resorcinol was the key for the success of our preparation of the target compound 5.",10.1055/s-2003-36262,2003-01-01,0.6795641048233992
Journal of the American Chemical Society,Highly Efficient Asymmetric Synthesis of Sitagliptin,"A highly efficient synthesis of sitagliptin, a potent and selective DPP-4 inhibitor for the treatment of type 2 diabetes mellitus (T2DM), has been developed. The key dehydrositagliptin intermediate 9 is prepared in three steps in one pot and directly isolated in 82% yield and >99.6 wt % purity. Highly enantioselective hydrogenation of dehydrositagliptin 9, with as low as 0.15 mol % of Rh(I)/(t)Bu JOSIPHOS, affords sitagliptin, which is finally isolated as its phosphate salt with nearly perfect optical and chemical purity. This environmentally friendly, 'green' synthesis significantly reduces the total waste generated per kilogram of sitagliptin produced in comparison with the first-generation route and completely eliminates aqueous waste streams. The efficiency of this cost-effective process, which has been implemented on manufacturing scale, results in up to 65% overall isolated yield.",10.1021/ja902462q,2009-06-09,0.6795396219672503
Synthesis,"Determination of the Absolute Configuration and a Practical Chiral Synthesis of 5-[5-(1-Methylethoxy)pyridin-2-yl]-5-methylimidazolidine-2,4-dione as a Novel Liver X Receptor β-Selective Agonist","We determined that the absolute configuration of 5-[5-(1-methylethoxy)pyridin-2-yl]-5-methylimidazolidine-2,4-dione (hydantoin) is the ( S )-form for the liver X receptor (LXR) β-selective agonist through X-ray crystal structure analysis of the hydantoin hydrogen bromide salt. Furthermore, we established a practical synthesis of the chiral hydantoin with 99% ee by the optical resolution of racemic methyl 2-amino-2-[5-(1-methylethoxy)pyridin-2-yl]propanoate with d -(–)-mandelic acid on a multi-kilogram scale. Finally, we improved the synthesis method of the LXR β-selective agonist.",10.1055/s-0036-1588700,2017-01-31,0.6795320035556093
European Journal of Organic Chemistry,Total Syntheses of (+)‐Valiolamine and (–)‐1‐<i>epi</i>‐Valiolamine from Naturally Abundant (–)‐Shikimic Acid,"Abstract Total syntheses of (+)‐valiolamine ( 1 ) and (–)‐1‐ epi ‐valiolamine ( 2 ) from the naturally abundant (–)‐shikimic acid are described. Ethyl 3‐ epi ‐5‐ O ‐methylsulfonyl‐shikimate ( 3 ), as the key common intermediate, was first synthesized in five steps in 74 % overall yield, and then converted into the targets 1 and 2 in seven steps in 48 and 41 % overall yield, respectively.",10.1002/ejoc.201300804,2013-08-15,0.6795276129408324
Tetrahedron,First example of the coupling of α-diazoketones with thiourea: a novel route for the synthesis of 2-aminothiazoles,,10.1016/j.tetlet.2008.02.068,2008-02-20,0.679521328572499
Organic Letters,"Asymmetric Synthesis of Vabicaserin via Oxidative Multicomponent Annulation and Asymmetric Hydrogenation of a 3,4-Substituted Quinolinium Salt","An efficient, asymmetric synthesis of the 5-HT2C agonist vabicaserin in four chemical steps and 54% overall yield from commercially available benzodiazepine was achieved. The synthesis was highlighted by a novel oxidative, multicomponent reaction to affect the quinolinium ring assembly in one step followed by an unprecedented asymmetric hydrogenation of a 3,4-substituted quinolinium salt.",10.1021/ol401029k,2013-06-10,0.6795084198988024
Journal of Organic Chemistry,Enantioselective Pd-Catalyzed α-Arylation of <i>N</i>-Boc-Pyrrolidine: The Key to an Efficient and Practical Synthesis of a Glucokinase Activator,"A short and practical synthesis of glucokinase activator 1 was achieved utilizing a convergent strategy involving S(N)Ar coupling of activated aryl fluoride 11 with hydroxypyridine 9. The key to the success of the synthesis was the development of a novel method for enantioselective formation of alpha-arylpyrrolidines during the course of the project. In this method, (-)-sparteine-mediated enantioselective lithiation of N-Boc-pyrrolidine was followed by in situ transmetalation to zinc and Pd-catalyzed coupling with aryl bromide 3, proceeding in 92% ee. This transformation allowed the preparation of compound 1 in a 31% overall yield over six steps.",10.1021/jo8006804,2008-05-29,0.6794968022098171
Journal of Organic Chemistry,"Practical, Stereoselective Synthesis of Palinavir, a Potent HIV Protease Inhibitor","Palinavir is a potent peptidomimetic-based HIV protease inhibitor. We have developed a highly convergent and stereoselective synthesis which is amenable to the preparation of multikilogram quantities of this compound. The synthetic sequence proceeds in 24 distinct chemical steps (with several integrated, multistep operations) from commercially available starting materials. No chromatographies are required throughout the process, and the final product is purified by crystallization of its dihydrochloride salt to >99% homogeneity.",10.1021/jo9702655,1997-05-01,0.6794801734602837
Organic Letters,Enantioselective Formal Total Synthesis of (−)-Quinagolide,"The enantioselective formal total synthesis of (−)-quinagolide has been accomplished in a linear sequence of 8 purification steps from pyridine. The key steps are (a) organocatalyzed Diels–Alder reaction for fixing all three stereocenters on piperidine ring; (b) protecting group enabled deoxygenation of isoquinuclidine skeleton under Birch reduction condition; (c) Lewis acid (TiCl 4 ) catalyzed intramolecular Friedel–Crafts cyclization of dicarboxylic acid; and (d) one-pot diastereoselective ketone reduction–intramolecular cyclization to form oxazolidinone which enables trans -geometry installation. During the course of the synthesis, an interesting reductive cleavage of the C–N bond in the electron-deficient isoquinuclidine skeleton under the Birch reduction conditions has been observed. This is the first synthetic effort to access the core skeleton of (−)-quinagolide.",10.1021/acs.orglett.9b03477,2019-10-30,0.6794312088841704
Organic Process Research & Development,"Practical Synthesis of Novel Cardioprotective Drug, CP-060<i>S</i>","A practical synthesis of a novel cardioprotective drug, CP-060 S, is described. Key intermediate ( S )- 7, a chiral carboxylic acid, was prepared from 3,5-di- tert -butyl-4-hydroxybenzaldehyde 2 by employing thiazolidinone cyclocondensation followed by selective crystallization from a diastereomeric salt mixture which was prepared by treating racemic 7 with ( S )-(−)- N -benzyl-α-methylbenzylamine 11 . Racemization of the ( R )- 7 -rich mixture, obtained from the mother liquid, by treatment with NaOH solution and subsequent resolution gave a second crop of ( S )- 7 . Resolving agent 11 was efficiently recovered from the resolution process and pure enough for recycling use. Chiral acid ( S )- 7 was converted to the corresponding methyl ester ( S )- 14, which was reduced with NaBH 4 −CaCl 2 to give alcohol intermediate ( S )- 4 . Subsequent mesylation, amination, and salt formation with fumaric acid afforded CP-060 S as pure enantiomer (99.8% ee) without any column chromatography.",10.1021/op000096h,2000-12-07,0.6793963957779645
Organic Letters,Concise Total Synthesis of Calothrixins A and B,"The concise total synthesis of calothrixins A and B has been accomplished by utilizing the one-pot formation of hexatriene as a key intermediate via the palladium-catalyzed tandem cyclization/cross-coupling reaction of triethyl(indol-2-yl)borate. In another key transformation, the indolo[3,2-j]phenanthridine core was prepared in high yield via Cu(I)-mediated 6π-electrocyclization.",10.1021/ol201107a,2011-05-31,0.6793942323512185
Journal of Organic Chemistry,Concise Means for Accessing an Advanced Precursor to 1-Deoxypaclitaxel,"A program directed toward a total synthesis of 1-deoxypaclitaxel is described. The most direct route consists of six steps from the previously described diketone 12 and proceeds in 18% overall yield. The transformations involved in reaching the target molecule 22 consist of stereoselective alpha-ketol generation, an EtAlCl(2)-catalyzed transannular hydride shift, regioselective monomesylation, and a Wagner-Meerwein 1,2-shift. The central issue of this synthesis is the sequential deployment of these highly controlled steps along the perimeter and across the interior gap of a nine-membered ring.",10.1021/jo048289g,2004-12-10,0.6793399372358576
Journal of Organic Chemistry,A Total Synthesis of OSW-1,"A new and practical method was developed to synthesize OSW-1, a natural saponin with potent antitumor activities, from (+)-dehydroisoandrosterone, l-arabinose, and D-xylose on gram scale. The synthesis was achieved in 10 linear steps with an overall yield of 6.4% starting from (+)-dehydroisoandrosterone.",10.1021/jo7018812,2007-12-08,0.6793337376691062
Organic Letters,Concise Route to the Chiral Pyrrolidine Core of Selective Inhibitors of Neuronal Nitric Oxide,"2-(((3R,4R)-4-(Allyloxy)-1-benzylpyrrolidin-3-yl)methyl)-6-(2,5-dimethyl-1H-pyrrol-1-yl)-4-methylpyridine (2), a key intermediate for the preparation of novel neuronal nitric oxide synthase (nNOS) inhibitors, is synthesized using diisopropyl (R)-(+)-malate as the starting material. The key steps involve a Frater-Seebach diastereoselective alkylation and a fast intramolecular cyclization.",10.1021/ol902109t,2009-10-27,0.6793247578023843
Tetrahedron,Controlling thiiranium intermediates—a new route to an iNOS inhibitor,,10.1016/j.tetlet.2009.07.059,2009-07-17,0.6793155684086163
Organic Letters,Highly Efficient and Scalable Synthesis of Clionamine D,"Herein we describe an efficient and scalable synthesis of clionamine D (4), a special member with autophagy bioactivity and an unprecedented spirobislactone side chain in the novel aminosteroid clionamines. This synthesis features a quick access to α-methylene-γ-lactone 8 and a Mn(OAc)3-mediated radical [3 + 2] reaction to assemble the unique spirobislactone unit. Clionamine D (4) can also serve as a key synthetic precursor to other clionamine members.",10.1021/ol500727c,2014-03-25,0.6792685681086792
Synthesis,Formal Synthesis of Aspergillide A from Tri-O-acetyl-d-glucal,"We describe an efficient synthesis of a key intermediate in the synthesis of aspergillide A from a commercially available, chiral starting material.",10.1055/s-0030-1260203,2011-09-02,0.6792598863603689
Organic Process Research & Development,Development of Scalable Processes for the Preparation of <i>N</i>-Methyl-3-Bromo-5-Methyl Pyrazole,"The development and optimization of two scalable routes to N- methyl-3-bromo-5-methyl pyrazole is described. The initial Sandmeyer route entailed a three-step sequence from crotonitrile and methyl hydrazine, proceeding through the 3-amino pyrazole intermediate. Due to the GTI liability of the 3-amino pyrazole intermediate, a tedious steam-distillation, and <30% overall yield, we developed a second-generation Sandmeyer-free approach from methyl crotonate and methyl hydrazine which leveraged a condensation, bromination, and oxidation sequence. Process development led to the improved preparation of N- methyl-3-bromo-5-methyl pyrazole with increased efficiency and overall yield. The isolation, handling, and storage of the final product was greatly improved through the generation of the triflic acid salt, and salt form studies are also discussed.",10.1021/acs.oprd.7b00091,2017-04-12,0.6792340527801961
Journal of Organic Chemistry,Synthesis of a TRPV1 Receptor Antagonist,A five-step synthesis of a TRPV1 receptor antagonist 1 is described. The key step involves a novel palladium-catalyzed amidation reaction of 4-chloro-1-methylindazole 8 with the benzyl urea 9 to form the unsymmetrically substituted urea 1.,10.1021/jo901943s,2009-11-23,0.679213768568163
Journal of Organic Chemistry,Asymmetric Synthesis of the Quinolizidine Alkaloid (−)-Epimyrtine with Intramolecular Mannich Cyclization and <i>N</i>-Sulfinyl δ-Amino β-Ketoesters,"A concise, six-step, enantioselective synthesis of (-)-epimyrtine employing the N-sulfinyl delta-amino beta-ketoester chiral building block is described.",10.1021/jo030208d,2003-09-18,0.6792123181743166
Tetrahedron,"Synthesis of functionalized furo[2,3-b]pyridines via the Pd-catalyzed coupling of acetylenes to iodopyridones. Preparation of a key intermediate to a new HIV protease inhibitor L-754,394",,10.1016/s0040-4039(00)78541-8,1994-12-01,0.6791849983955375
Organic Process Research & Development,Development of a Scalable Manufacturing Process for AB-343 Drug Substance: A Potential Candidate for the Treatment of Coronavirus Infections,"A scalable process for manufacturing of the anticoronavirus clinical candidate AB-343 has been developed. The lactam-containing subunit of the molecule was prepared using a novel synthetic route involving a nitro-Michael reaction and a rhodium-catalyzed nitro group hydrogenation followed by in situ translactamization sequence as a key transformation. The drug substance was assembled via sequential amide coupling and deprotection reactions, followed by a final dehydration of a primary amide to the corresponding nitrile using T3P. AB-343 drug substance was successfully manufactured on a multikilogram scale using this route, which was suitable for supporting IND-enabling studies and Phase I clinical development.",10.1021/acs.oprd.4c00528,2025-02-25,0.6791790437608626
Organic Letters,Synthesis of the Core Ring System of the Antiosteoporotic Citrofulvicin,"Synthesis of the octacyclic ring system of citrofulvicin is described in nine steps from readily available starting materials. Blocking undesired intramolecular cyclization of a reactive β-diketone intermediate by transient incorporation of a dithiolane ring led to the formation of the requisite 1-hydroxy-2,4,6-trioxaadamantane ring system of citrofulvicin.",10.1021/acs.orglett.1c01216,2021-06-04,0.6791626588728241
Tetrahedron,Enantioselective total synthesis of didesepoxyrhizoxin,The first synthesis of the antitumor macrolide didesepoxyrhizoxin is described.,10.1016/0040-4039(95)00926-4,1995-07-01,0.6791254012862851
Organic Process Research & Development,Production of (<i>R</i>)-Aminoglutethimide:  A New Route from 1-Chloro-4-nitrobenzene,"The development of a short, safe and enantioselective route for the preparation of ( R )-aminoglutethimide is described. The process was designed for economic large-scale manufacture of the bulk drug substance to acceptable quality standards, to allow clinical evaluation of the single enantiomer over the existing racemate. ( R )-Aminoglutethimide was prepared from 1-chloro-4-nitrobenzene using a six-stage synthetic sequence, via chemoresolution of key intermediate racemic 4-cyano-4-(4-nitrophenyl)hexanoic acid using (−)-cinchonidine. The process allowed for preparation of several kilograms of the precursor ( R )-nitroglutethimide, to cGMP at pilot-plant scale, along with demonstration of the final hydrogenation step to ( R )-aminoglutethimide in the laboratory. This route avoids the problems of hazardous nitration technology, and therefore regio-isomer contamination of the product, associated with other procedures. The resolution chemistry described represents an improvement on literature procedures. Optimisation of the asymmetric Michael addition offers an attractive alternative approach.",10.1021/op9900075,1999-10-28,0.6791252167606957
Angewandte Chemie International Edition,"Short, Enantioselective Total Synthesis of Chatancin","An enantioselective total synthesis of the polycyclic diterpene (+)-chatancin, a potent PAF antagonist, is reported. Proceeding in seven steps from dihydrofarnesal, this synthetic route was designed to circumvent macrocyclization-based strategies to complex, cyclized cembranoids. The described synthesis requires only six chromatographic purifications, is high yielding, and avoids protecting-group manipulations. An X-ray crystal structure of this fragile marine natural product was obtained.",10.1002/anie.201410443,2014-12-02,0.6791102034292226
Organic Process Research & Development,Some Items of Interest to Process R&amp;D Chemists and Engineers,"how the synthesis of a nonpeptidic R v β 3 antagonist was developed and performed on multikilogram scale.The retrosynthetic analysis is shown in the following scheme whereby two key fragments were prepared and coupled in a convergent late-stage Wittig olefination reaction.Manipulation to the desired product involved reduction of the product enone from the Wittig coupling followed by hydrolysis of the ester.The pyridoazepine fragment was prepared from N-Boc 6-chloro-2-aminopyridine via directed ortho-metalation/alkylation followed by in situ cyclization.A Suzuki reaction was then used to attach the propionaldehyde side chain.The chiral β-keto phosphorane was prepared from asymmetric methanolysis of a 3-substituted glutaric anhydride using quinidine followed by functional group manipulation.The drug substance was prepared in 17% yield (longest linear sequence) and multikilogram methods are described in the paper. Chiral β-Amino Acid SynthesisIn a further ""process paper"" from the Merck group (J.Org.Chem.2005Chem., 70, 1949) ) a stereoselective synthesis of an (R)β-amino acid A is described.The preparation involves methanolysis of a key β-lactam (followed by hydrogenation and saponification).In turn the chirality of the β-lactam was installed via enantioselective reduction of the β-ketoacid",10.1021/op0500584,2005-05-01,0.6790649781929101
Tetrahedron,"A new, simple route to tetracyclic intermediates for the synthesis of diterpenoid alkaloids",,10.1016/s0040-4039(01)98905-1,1968-01-01,0.6790525422430562
Synthesis,Synthesis of Ferrocenesulfonyl Chloride: Key Intermediate toward Ferrocenesulfonamides,"Abstract Ferrocenesulfonyl chloride is the key intermediate in the synthesis of ferrocenesulfonamides, a family of underexplored derivatives. A one-pot synthesis of this compound, able to easily deliver multigram quantities of product, is reported. An original protocol for the synthesis of ferrocenesulfonamides is described along with highlighting the reactivity difference between arene and ferrocenesulfonyl chlorides. Finally, an example of diastereoselective deprotolithiation of chiral ferrocenesulfonamides is described.",10.1055/a-1478-7002,2021-04-09,0.6789380087644563
Organic Letters,A Concise Enantioselective Synthesis of (−)-Ranirestat,"A concise, enantioselective synthesis of the potent aldose reductase inhibitor ranirestat (1) is reported. The synthesis was accomplished employing inexpensive, commercially available starting materials. A palladium-catalyzed asymmetric allylic alkylation (Pd-AAA) of malonate 4 was utilized as a key transformation to construct the tetrasubstituted chiral center in the target.",10.1021/ol100167w,2010-02-11,0.6789364482809622
Journal of the American Chemical Society,Total Synthesis of (±)-Aspergilline A,The total synthesis of (±)-aspergilline A (1) is described. Key features of the synthesis include pyrrolinone formation via reaction of an intermediate propargyl amine with a methyl malonyl chloride derived ammonium enolate and a formal [3+2] cycloaddition between an imidate and cyclopropenone.,10.1021/jacs.7b12570,2017-12-13,0.6789050669119447
Journal of the American Chemical Society,Enantioselective Synthesis of Sealutomicin C,The sealutomicins are a family of anthraquinone antibiotics featuring an enediyne (sealutomicin A) or Bergman-cyclized aromatic ring (sealutomicins B-D). Herein we report the development of an enantioselective organocatalytic method for the synthesis of dihydroquinolines and the use of the developed method in the total synthesis of sealutomicin C which features a transannular cyclization of an aryllithium onto a γ-lactone as a second key step.,10.1021/jacs.4c02969,2024-06-17,0.67886943725861
Organic Letters,A Highly Stereoselective and Scalable Synthesis of <scp>l</scp>-allo-Enduracididine,"A highly stereoselective and scalable synthesis of L-allo-enduracididine from hydroxyproline derivative is described. Pyrrolidine oxidation and reductive ring opening are the key steps in the synthesis. Compared to previously reported approaches, the current route affords l-allo-enduracididine in 10 steps from 3 in 31% overall yield with >50:1 diastereoselectivity.",10.1021/acs.orglett.5b02362,2015-09-10,0.6788485114665843
Organic Process Research & Development,Development of Two Complementary Syntheses for a Privileged CGRP Receptor Antagonist Substructure,"1-(Piperidin-4-yl)-1 H -imidazo[4,5- b ]pyridin-2(3 H )-one ( 1 ) is a privileged substructure found in >1000 unique CGRP receptor antagonists. Two practical and efficient syntheses of 1 are described from complementary starting materials. One route features a chemoselective reductive amination, while the second route utilizes a Pd-catalyzed amination using an ammonia surrogate to overcome an issue of poor selectivity.",10.1021/op2003634,2012-01-06,0.6788329190140998
Organic Letters,Efficient Asymmetric Synthesis of the Vasopeptidase Inhibitor BMS-189921,"[reaction: see text] An efficient asymmetric synthesis of the vasopeptidase inhibitor BMS-189921 was accomplished. Two short enantioselective syntheses of the common key intermediate (S)-alpha-aminoazepinone 6b were developed. Olefin 3 was converted to 6b via asymmetric hydrogenation. Alternatively, enyne 12 was converted to racemic alpha-aminoazepinone 15b, which was transformed to 6b by a practical dynamic resolution.",10.1021/ol0352308,2003-08-01,0.678826633154275
Journal of Organic Chemistry,Asymmetric Total Synthesis of the Caribbean Fruit Fly Pheromone (+)-Epianastrephin,"An asymmetric total synthesis of (+)-epianastrephin ( 1 ) from the chiral benzamide 2 (15 steps, 9.5% overall yield) is described. Birch reduction−alkylation of 2 with methyl iodide gave 3 in 91% yield as a single diastereomer. Cyclohexadiene 3 was converted to olefinic carboxylic acid 6b, and a tandem iodolactonization−radical reduction sequence provided lactone 8 with three contiguous stereogenic centers. Chiral HPLC comparison of diol 12b, the immediate precursor to (+)-epianastrephin ( 1 ), with 12b prepared from racemic epianastrephin demonstrated that 1 had been prepared with >98% ee.",10.1021/jo960568j,1996-01-01,0.678805354696457
Organic Process Research & Development,Scalable Atroposelective Synthesis of MRTX1719: An Inhibitor of the PRMT5/MTA Complex,"High Resolution Image Download MS PowerPoint Slide MRTX1719 was identified as a potent inhibitor of the PRMT5/MTA complex, designed to selectively target MTAP -deleted cancers. A scalable synthesis of this atropisomeric compound and an efficient isolation of the desired isomer were required to support Phase 1 clinical trials, and this was established through further development of the racemic medicinal chemistry route. In the key step, the desired ( M )-atropisomer of MRTX1719 was amplified from racemic API by combining crystallization (20 °C) and racemization (160 °C, 4 min). Concurrent execution of these, ostensibly incompatible, operations was enabled by a continuous flow setup (SPACE = S imultaneous P rocessing of A ntagonistic C hemical E vents) providing 98.4% e.e. of ( M )-atropisomer in 75% yield from racemic API on 12 kg scale. Process development targeting earlier steps of the API synthesis led to several impactful revisions including desymmetrization of 4-chlorobenzamide to access the 6-substituted-4-(aminomethyl)phthalazin-1(2 H )-one ring system, improved borylation conditions (Suzuki–Miyaura or photocatalytic), and demonstration of an economically viable route to the challenging pentasubstituted benzene from 1,4-difluorobenzene and cyclopropyl methyl ketone.",10.1021/acs.oprd.3c00072,2023-05-10,0.6788010795355756
Synthesis,Efficient Synthesis of the Immunosuppressive Agent FTY720,"The concise and practical synthesis of the biologically important FTY720 was achieved employing the palladium-catalyzed Sonogashira coupling reaction as a key step. The commercial tris(hydroxymethyl)aminomethane was converted to alkyne 2 via a three-step synthesis. The coupling reactions of alkyne 2 with aryl iodide 3, followed by subsequent hydrogenation of the internal alkyne and removal of the protecting groups provided FTY720 in high overall yield.",10.1055/s-2006-926342,2006-01-01,0.6787802458768021
Tetrahedron,A simple route for synthesis of 4-phospho-d-erythronate,,10.1016/j.tetlet.2011.02.045,2011-02-15,0.6787175211814321
Synlett,Short Synthesis of Phenylpropanoid Glycosides Calceolarioside A and Syringalide B,An efficient and practical three-step synthesis of phenylpropanoid glycosides calceolarioside A and syringalide B in &gt;62% overall yield is disclosed. The key step involves the chemoselective and regio­selective direct O-4 cinnamoylation of unprotected 2-phenylethyl-β-d-glucosides with cinnamic anhydrides using a chiral 4-pyrrolidinopyridine organocatalyst. This approach serves as a model for the short synthesis of phenylpropanoid glycosides acylated at O-4 without protection/deprotection steps.,10.1055/s-0036-1591753,2018-01-31,0.6787170583876873
European Journal of Organic Chemistry,Stereodivergent Syntheses of All Stereoisomers of (−)‐Shikimic Acid: Development of a Chiral Pool for the Diverse Polyhydroxy‐cyclohexenoid (or ‐cyclohexanoid) Bioactive Molecules,Abstract Novel stereodivergent total syntheses of all the seven stereoisomers of (−)‐shikimic acid [(−)‐SA 1 ] have been systematically performed. (+)‐ ent ‐SA ent ‐ 1 was synthesized from (−)‐SA 1 via 9 steps in 31 % overall yield; (−)‐3‐ epi ‐SA 2 was synthesized from (−)‐SA 1 via 5 steps in 66 % overall yield; (+)‐3‐ epi ‐ ent ‐SA ent ‐ 2 was synthesized from (−)‐SA 1 via 7 steps in 43 % overall yield; (−)‐4‐ epi ‐SA 3 was synthesized from (−)‐SA 1 via 11 steps in 32 % overall yield; (+)‐4‐ epi ‐ ent ‐SA ent ‐ 3 was synthesized from (−)‐SA 1 via 7 steps in 42 % overall yield; (−)‐5‐ epi ‐SA 4 was synthesized from (−)‐SA 1 via 6 steps in 56 % overall yield; and (+)‐5‐ epi ‐ ent ‐SA ent ‐ 4 was synthesized from (−)‐SA 1 via 12 steps in 29 % overall yield. The stereochemistry of all the above seven stereoisomers of (−)‐SA 1 were further studied by two dimensional (2D) 1 H NMR technique.,10.1002/ejoc.202100653,2021-06-28,0.6787031075317886
Organic Process Research & Development,Commercial Synthesis of Azilsartan Kamedoxomil: An Angiotensin II Receptor Blocker,"A commercially viable process for the preparation of azilsartan kamedoxomil, an angiotensin II receptor blocker, has been developed. The present work describes the novel synthesis of azilsartan medoxomil from amidoxime methyl ester. The present work also describes the improved synthesis of amidoxime methyl ester and azilsartan kamedoxomil. This process features a high overall yield (36%) with 99.52% HPLC purity.",10.1021/op500357r,2015-03-13,0.6786952491231254
Tetrahedron,An efficient route to functionalized dienes for decalin synthesis,,10.1016/s0040-4039(97)00823-x,1997-06-01,0.6786435139496675
Organic Process Research & Development,"Development of a Scalable Synthesis for the Potent Kinase Inhibitor <b>BMS-986236</b>; 1-(5-(4-(3-Hydroxy-3-methylbutyl)-1<i>H</i>-1,2,3-triazol-1-yl)-4-(isopropylamino)pyridin-2-yl)-1<i>H</i>-pyrazolo[3,4-<i>b</i>]pyridine-5-carbonitrile","A scalable route to 1-(5-(4-(3-hydroxy-3-methylbutyl)-1 H -1,2,3-triazol-1-yl)-4-(isopropylamino)pyridin-2-yl)-1 H -pyrazolo[3,4- b ]pyridine-5-carbonitrile ( 1, BMS-986236 ) was developed by incorporating an alternate azide intermediate following safety-driven processes. The newly developed process involved mitigating safety hazards and eliminating the column chromatography purification. The issue of trace metal contamination in the final API observed in the first-generation synthesis has been overcome.",10.1021/acs.oprd.9b00023,2019-03-27,0.6786391239483793
Organic Process Research & Development,"Development of a Practical Synthesis of a Functionalized Pyrrolo[2,1-f][1,2,4]triazine Nucleus","Functionalized pyrrolotriazine 1b is a key heterocyclic building block in the synthesis of BMS-690514, a potent anticancer agent. Described herein are our development activities that led to the efficient preparation of 1b on a large scale. The key transformations include a selective C-alkylation of an oxalacetate salt with a hydrazonyl bromide to form a 2-hydrazonoethyl-3-oxosuccinate, followed by cyclodehydration to an aminopyrrole. Subsequent deprotection and condensation with formamidine afforded the pyrrolotriazine scaffold. Further elaboration of this core provided the desired pyrrolotriazinyl amine.",10.1021/op300252n,2012-10-15,0.6786348243469397
Organic Process Research & Development,New Method to Large-Scalable Preparation of the Key Chiral Cyclohexane <i>cis</i>-Diamine Intermediate for Edoxaban,"A new synthesis of tert -butyl (1 R,2 S,5 S )-2-amino-5-(dimethylcarbamoyl)cyclohexylcarbamate, a key intermediate of edoxaban, is disclosed. This compound is a cyclohexane cis -diamine whose structure is a synthetic challenge. The known synthetic methods suffer from drawbacks, such as low yield, long reaction times, as well as excessive use of NaN 3 . The new method includes a total of nine steps starting from the known compound, (1 S,4 S,5 S )-4-bromo-6-oxabicyclo[3.2.1]octan-7-one, whose γ-butyrolactone frame is ring-opened to form trans -3-azido-4-hydroxy cyclohexane after the first two steps. Subsequent oxidation leads to the formation of a cyclohexanone, which is then transformed to cis -diamine through enzyme-catalyzed asymmetric reductive amination, acylation with CbzCl, and reduction of the azido group successively. The target, tert -butyl (1 R,2 S,5 S )-2-amino-5-(dimethylcarbamoyl)cyclohexylcarbamate, is finally formed through acylation with (Boc) 2 O, followed by deprotection of the Cbz group using hydrogenation.",10.1021/acs.oprd.4c00039,2024-06-14,0.6786320903693142
Synthesis,Towards the Synthesis of the Skeleton of Salvianolic Acid D,"A successful synthesis of the acid part of salvianolic acid D is described (eight steps from isovanillin, 22% overall yield). The benzaldehyde key intermediate was obtained in six steps in 52% overall yield and was converted into the trimethylated precursor molecule using the Knoevenagel procedure. Finally, the acid part of salvianolic acid D was obtained by the exhaustive deprotection of the methyl groups with boron tribromide.",10.1055/s-2006-926332,2006-01-01,0.6786219040574717
Tetrahedron,A new and efficient route to 4-carboxymethylcoumarins mediated by vinyltriphenylphosphonium salt,,10.1016/s0040-4039(98)00206-8,1998-04-01,0.6786041120377149
Journal of Organic Chemistry,Highly Efficient and Practical Syntheses of Lavendamycin Methyl Ester and Related Novel Quinolindiones,"The novel 7-(N-formyl-, 7-(N-acetyl-, and 7-(N-isobutyrylamino)-2-methylquinoline-5,8-diones were synthesized in excellent overall yields in three steps via the nitration of the commercially available 8-hydroxy-2-methylquinoline followed by a reduction-acylation step and then oxidation. Acid hydrolysis of 7-(N-acetylamino)-2-methylquinoline-5,8-dione (14a) afforded the novel 7-aminoquinoline-5,8-dione 7 in excellent yields. Due to our efficient preparation of dione 14a, we now report a short and practical method for the total synthesis of the potent antitumor agent lavendamycin methyl ester (1b) with an excellent overall yield.",10.1021/jo960794t,1996-01-01,0.678551834676566
Journal of Organic Chemistry,Total Synthesis of (−)-Orthodiffenes A and C,"The efficient and concise synthesis of (-)-orthodiffenes A and C has been accomplished for the first time in eight steps from readily available chiral synthons, D-mannose and D-ethyl lactate. Our work confirmed the complete structure of orthodiffenes A and C, including their absolute stereochemistry. The key steps of our total synthesis involved cis-fused tetrahydrofuran cyclization, one-pot deprotection-lactonization, and intramolecular benzoyl migration according to a biosynthetic hypothesis of orthodiffenes.",10.1021/jo301829p,2012-10-11,0.6785060274102432
Journal of Organic Chemistry,Synthesis of the C29−C44 Portion of Spongistatin 1 (Altohyrtin A),"Two synthetic approaches to the C29-C44 portion of spongistatin 1 (altohyrtin A) have been developed. The key step of the first approach relies on the Claisen rearrangement of glucal 18 to provide ester 20a. This intermediate was advanced to silyl enol ether 30, which was coupled under Mukaiyama aldol conditions with aldehyde 3. Cyclization of this aldol adduct completed our first synthesis of the C29-C44 portion of spongistatin 1, requiring 25 total steps and occurring in 2.4% yield over the longest linear sequence (21 steps). We have also developed a second-generation approach based on the C-glycosidation of glucal 43. Through equilibration of the corresponding C-glycosides 49a/b and 50a/b the desired C-glycoside (50a) was obtained in good yield. Aldol condensation of this ketone provided cyclization precursor 67, which undergoes acid-catalyzed ketalization to close the E-ring of the spongistatins. An oxidation/reduction protocol was employed to set the C37 stereocenter. Protection of the C37 carbonol and selective unmasking of the C44 carbonol completed our second generation synthesis. This approach requires 27 steps and occurred in 13.2% yield over the longest linear sequence (18 steps).",10.1021/jo0002801,2000-06-01,0.6784969171224029
Tetrahedron,"A novel and efficient synthesis of chiral C2-symmetric 1,4-diamines",,10.1016/j.tetlet.2008.11.071,2008-11-26,0.678484046279114
Journal of the American Chemical Society,Total Synthesis of (+)-Nakadomarin A,"The total synthesis of (+)-nakadomarin A is described. A three-component cycloaddition of a hydroxylamine, aldehyde, and cyclopropane to form a highly functionalized tetrahydro-1,2-oxazine serves as the foundation for this synthesis. The resulting oxazine is formed as a single diastereomer with the absolute configuration being dictated by the chirality of the cyclopropane. Other key steps include: desymmetrization of a malonate by reduction, Heck cyclization and pyrrolidine formation, and ring-closing metathesis to form both cycloalkenes. Overall, the synthesis required 23 linear steps from the cyclopropane, which in turn is available (six steps) in optically pure form from commercially available d-mannitol.",10.1021/ja068047t,2007-01-11,0.6784724033969562
Synthesis,A Convenient Route to Substituted Phenylalanines,All articles of this category A four-step route to phenylalanines substituted on the aryl moiety is reported starting from aromatic aldehydes. Some novel methyl 2-nitro-3-arylpropionates have been isolated as intermediates in the synthesis and are described.,10.1055/s-1987-27962,1987-01-01,0.6784548403335943
Organic Process Research & Development,Novel Synthesis of Antiobesity Drug Lorcaserin Hydrochloride,"A novel synthesis of antiobesity drug lorcaserin hydrochloride was accomplished in six steps. N -protection of 2-(4-chlorophenyl)ethanamine with di- tert -butyl dicarbonate, N -alkylation with allyl bromide, deprotection, intramolecular Friedel–Crafts alkylation, chiral resolution with l -(+)-tartaric acid, and the final salification led to the target molecule lorcaserin hydrochloride in 23.1% overall yield with 99.9% purity and excellent enantioselectivity (>99.8% ee). This convenient and economical procedure is remarkably applicable for scale-up production.",10.1021/acs.oprd.5b00144,2015-08-14,0.6784452593581103
Synthesis,"First Stereoselective Synthesis of (6R,7R,8S)-8-Chlorogoniodiol","A stereoselective synthesis of (6R,7R,8S)-8-chlorogoniodiol has been achieved in a linear sequence of 12 steps and 19.8% overall yield from cinnamyl alcohol. The key steps include Sharpless asymmetric epoxidation, regioselective ring opening of epoxide, indium-mediated Barbier allylation, and Still–Gennari olefination.",10.1055/s-0036-1588972,2017-03-17,0.678440065795598
Organic Letters,Enantioselective Total Synthesis of (−)-Salinosporamide A (NPI-0052),"A novel enantioselective total synthesis of 20S proteasome inhibitor Salinosporamide A (NPI-0052; 1) is presented. Key features include intramolecular aldol cyclization of 6 to simultaneously generate the three chiral centers of advanced intermediate 5, cyclohexene ring addition using B-2-cyclohexen-1-yl-9-BBN, and inversion of the C-5 stereocenter by oxidation followed by enantioselective enzymatic reduction.",10.1021/ol0706051,2007-05-12,0.678401159610159
Journal of Organic Chemistry,Chemoenzymatic Synthesis of α-Hydroxy-β-methyl-γ-hydroxy Esters: Role of the Keto−Enol Equilibrium To Control the Stereoselective Hydrogenation in a Key Step,"Alpha-hydroxy-beta-methyl-gamma-hydroxy esters not only are found in many natural products and potent drugs but also are useful intermediates in organic synthesis due to their highly functionalized skeleton that can be further manipulated and applied in the synthesis of many compounds with remarkable biological activities. This work was based on a chemoenzymatic approach to obtain these molecules with three contiguous stereogenic centers in a highly enantio- and diastereoselective way. Two distinct linear routes were proposed in which the key steps in both routes consisted of initial stereocontrolled ketoester bioreduction followed by unsaturated carbonyl bioreduction or reduction with Pd-C. Other key reactions in the synthesis include a Wasserman protocol for chain homologation and a Mannich-type olefination with maintenance of enantiomeric excess for all intermediates during the sequence. Whereas route A gave exclusively the skeleton with 3R,4R,5S configuration (99% ee and 11.5% global yield after 7 steps), route B gave the skeleton with 3R,4R,5S and 3R,4S,5R configurations (dr 1:12, 98% ee and 20% global yield after 5 steps).",10.1021/jo902227f,2010-02-09,0.6783656638514884
Organic Process Research & Development,Fulvestrant: From the Laboratory to Commercial-Scale Manufacture,"The development of a commercial manufacturing process for fulvestrant (the active ingredient in ‘Faslodex’) is described. Key steps in the synthesis are stereoselective 1,6-addition of an organocuprate to a steroidal dienone followed by copper-mediated aromatisation of the A-ring. The strategy for dealing with noncrystalline intermediates is outlined. The production of drug substance of acceptable quality is critically dependent on limiting the formation of key impurities. The origin of these impurities is discussed, and measures to prevent or control their formation are described.",10.1021/op900315j,2010-03-29,0.6783592631722525
Journal of Organic Chemistry,"α,β-Unsaturated Diazoketones as Platforms in the Asymmetric Synthesis of Hydroxylated Alkaloids. Total Synthesis of 1-Deoxy-8,8a-diepicastanospermine and 1,6-Dideoxyepicastanospermine and Formal Synthesis of Pumiliotoxin 251D","A versatile and concise approach for the stereoselective synthesis of mono-, di-, and trihydroxylated indolizidines is presented in four to six steps from Cbz-prolinal and a diazophosphonate. The key steps involved a Wolff rearrangement, followed by a stereoselective dihydroxylation/epoxidation reaction, from an α,β-unsaturated diazoketone. The strategy also permits extension to the synthesis of many natural hydroxylated indolizidine alkaloids as demonstrated in the formal synthesis of pumiliotoxin 251D.",10.1021/jo301967w,2012-10-15,0.6782645036669152
Organic Process Research & Development,"Process Development of a Scaleable Route to (2<i>R</i>)-[3-(2-Aminopropyl)-1<i>H</i>-indol-7-yloxy]-<i>N,N</i>-diethylacetamide:  A Key Intermediate for AJ-9677, a Potent and Selective Human and Rat β<sub>3</sub>-Adrenergic Receptor Agonist","(2 R )-[3-(2-Aminopropyl)-1 H -indol-7-yloxy]acetic acid ( 2 ) is the left-hand side segment of AJ-9677, which is a potent and selective human and rat β 3 -adrenergic receptor agonist. Herein, we describe the process development of a scaleable synthetic route to the corresponding N,N -diethylacetamide derivative 3 of 2 from 7-benzyloxy-1 H -indole ( 4 ). Reaction of the indole Grignard reagent 12 generated from 4 and methylmagnesium bromide with the N -Fmoc- d -alanyl chloride 22, followed by reduction of the resulting crude 3-acylindole 26 with NaBH 4 in a mixture of MeCN and 2-PrOH at refluxing temperature and subsequent treatment with oxalic acid gave the oxalate of the N -deprotected product, (2 R )-3-(2-aminopropyl)-7-benzyloxy-1 H -indole [( R )- 7 ] as a crystalline material in 60% yield. After N -protection of the ( R )- 7 by Boc group, the (2 R )-3-[2-(Boc-amino)propyl]-1 H -indole 30 was hydrogenated to provide the (2 R )-3-(2-aminopropyl)-7-hydroxy-1 H -indole 31, which was subsequently alkylated with ClCH 2 CONEt 2 to give 32 in 91% yield. Finally, treatment of 32 with oxalic acid afforded the desired 3 in 79% in >99% ee.",10.1021/op0341869,2004-02-12,0.678194672452803
Organic Process Research & Development,"Practical Synthesis of (3a<i>R</i>, 9b<i>R</i>)-8-Fluoro-7-(perfluoropropan-2-yl)-9b-(phenylsulfonyl)-2,3,3a,4,5,9b-hexahydro-1<i>H</i>-benzo[e]indole: An Advanced Intermediate to Access the RORγt Inverse Agonist <b>BMT-362265</b>","A practical and scalable route to (3a R, 9b R )-8-fluoro-7-(perfluoropropan-2-yl)-9b-(phenylsulfonyl)-2,3,3a,4,5,9b-hexahydro-1 H -benzo[e]indole 10, an advanced intermediate en route to the synthesis of the RORγt inverse agonist, BMT-362265, is described starting from fluorobenzene. The synthesis involved the screening of multiple synthetic routes for their feasibility and scalability. We also demonstrate the utility of an annulating reagent, ( R )- N -(2-chloroethyl)-2-methylpropane-2-sulfinamide, for the diastereoselective synthesis of tricyclic pyrrolidine intermediates 24 and 36 on a multigram scale.",10.1021/acs.oprd.1c00019,2021-03-16,0.6781129491116067
Journal of Organic Chemistry,Stereocontrolled Synthesis of the JKLM Ring Fragment of Ciguatoxin,"A highly stereocontrolled synthesis of the JKLM ring fragment of ciguatoxin has been achieved. The present synthesis starts with methyl 4,6- O -benzylidene-2-deoxy-2- C -methyl-α- d -altropyranoside, whose configurations and substituents at C2−C5 correspond to those at C46−C49 of ciguatoxin, and involves as the key step base-induced 7- endo selective cyclization of a hydroxy epoxide for the efficient construction of the fully substituted oxepane ring K. Construction of the spiroether ring M was achieved by introduction of an allyl group to the ring L lactone followed by asymmetric dihydroxylation to install the C54 stereogenic center and acid-induced spiroketalization to furnish the protected KLM ring system. Finally, ring J was constructed by the method of Nicolaou to complete the synthesis of the JKLM ring fragment. The synthesis of a carboxylic acid derivative and its conjugation to carrier proteins to give an artificial antigen for development of an immunoassay system for the parent toxin molecule are also reported.",10.1021/jo990988j,1999-12-01,0.678105039023665
Organic Process Research & Development,Development of the Synthetic Route to PF-06878031 Part 1: Selective Alkylation Route,"The target compound PF-06878031 is a key structural fragment of a range of oral late-stage glucagon-like peptide-1 receptor agonists (GLP-1-RA) under development in our laboratories for the indications of type-2 diabetes mellitus (T2DM) and weight loss. This article describes the identification of a selective alkylation route and development of a process, capable of delivering multikilo quantities of PF-06878031 . Process development afforded improved safety, increased yield, reduced step count, and lowered PMI. The new process has been scaled up at multiple facilities to generate >1.5MT of high purity PF-06878031 .",10.1021/acs.oprd.4c00053,2024-04-19,0.6780201893424577
European Journal of Organic Chemistry,A Stereoselective Synthesis of an Imino Glycal: Application in the Synthesis of (–)‐1‐<i>epi</i>‐Adenophorine and a Homoimindosugar,"A concise stereoselective synthesis of an imino glycal is described in 8 steps starting from 1,2‐anhydro‐3,4,6‐tri‐ O ‐benzyl‐ d ‐glucopyranose. The utility of the imino glycal has been demonstrated in synthesis of (–)‐1‐ epi ‐adenophorine and a homoiminosugar as a glycosidase inhibitor. The important features of the developed route include high yields, high stereoselectivity, and application in the synthesis of other iminosugars. Additionally, a new synthon 2‐nitro‐imino glycal has also been synthesized which could act as valuable synthon in carbohydrate chemistry.",10.1002/ejoc.201801241,2018-09-16,0.6780142454880207
Organic Letters,An Efficient and Stereoselective Synthesis of Xerulin <i>via</i> Pd-Catalyzed Cross Coupling and Lactonization Featuring (<i>E</i>)-Iodobromoethylene as a Novel Two-Carbon Synthon,"[structure: see text] Xerulin, an inhibitor of cholesterol biosynthesis, has been synthesized from commercially available (E)-1-bromopropene, acetylene, and propynoic acid in five steps (longest linear sequence) in 30% overall yield and >96% stereoselectivity. The preparation of (E)-iodobromoethylene and its use in the Pd-catalyzed cross coupling are two of the novel aspects of the synthesis reported herein.",10.1021/ol990336h,1999-12-15,0.6779906044334183
Tetrahedron,"Synthesis of 6-(3-methylpyrrol-1-yl)-9-β-D-ribofuranosyl purine, a novel metabolite of zeatin riboside",,10.1016/s0040-4039(00)88821-8,1990-01-01,0.67798573417329
Organic Process Research & Development,Kilo-Scale Synthesis of the Dinucleotide DNA Methyltransferase Inhibitor Guadecitabine,"Process research and development directed toward a scalable, solution-phase synthesis of the novel dinucleotide DNA methyltransferase inhibitor guadecitabine is described. Highly selective enzyme-mediated 5′-OH acetylation of a decitabine N, N -dimethylformamidine derivative and isolation of the penultimate intermediate as the tert -butylamine salt were key achievements of the development program. This route allowed kilo-scale GMP production of clinical-grade guadecitabine (SGI-110).",10.1021/acs.oprd.4c00072,2024-05-10,0.6779207372970146
Organic Process Research & Development,Improved Process for the Preparation of 6-Chloro-5-(2-chloroethyl)oxindole,The current process for ziprasidone involves preparation and isolation of the key intermediate 6-chloro-5-(2-chloroethyl)oxindole. An improved process for the synthesis of this intermediate is reported here. The new process involves use of a novel Lewis acid-mediated selective deoxygenation of the precursor ketone with tetramethyldisiloxane. The new method affords the desired compound in a one-pot process obviating the need for isolation of the potentially hazardous precursor ketone. This process was successfully scaled up to multikilo scale.,10.1021/op800105j,2008-09-20,0.6778894960860282
Organic Process Research & Development,Development of a New Synthesis for the Large-Scale Preparation of Triple Reuptake Inhibitor (−)-GSK1360707,"The triple reuptake inhibitor, GSK1360707, was synthesized via an efficient, scalable route, which features a vinyl triflate Suzuki coupling followed by a single-step, double alkylative cyclopropanation with a dihalomethane. Also, a mechanistic understanding of the Suzuki reaction (as it relates to the control of a polychlorinated biphenyl impurity) is discussed.",10.1021/op100139f,2010-06-22,0.6778731449334052
Organic Process Research & Development,"Development of Scalable Synthesis of 5-Butyl-4-(4-methoxyphenyl)-6-phenylpyrimidin-2-amine (WQE-134), a Dual Inhibitor of Nitric Oxide and Prostaglandin E<sub>2</sub> Production","We report a scalable efficient synthesis of 5-butyl-4-(4-methoxyphenyl)-6-phenylpyrimidin-2-amine (WQE-134), a dual inhibitor of nitric oxide and prostaglandin E 2 production with potent anti-inflammatory properties. The original five-step synthesis (40% overall yield) was based on two Suzuki–Miyaura reactions and required chromatographic purification of both the intermediate and final products. The novel synthetic pathway is based on cyclization of 2-butyl-1-(4-methoxyphenyl)-3-phenylpropane-1,3-dione with guanidinium methanesulfonate using Eaton’s reagent (P 2 O 5 /MsOH) at 50 °C. The two-step synthesis (34% overall yield) can be performed on a multigram to kilogram scale, and purification of the final product consists of simple extraction (dichloromethane) and crystallization (ethyl acetate and methanol).",10.1021/acs.oprd.0c00324,2020-08-28,0.6778582501344378
Tetrahedron,"Development of scalable processes to prepare a key chiral, nonracemic intermediate en route to LpxC inhibitors for Gram-negative infections",,10.1016/j.tetlet.2024.155336,2024-10-24,0.6778575564895591
Organic Process Research & Development,"An Improved Process for the Preparation of 4,4-Dimethyloxazolidine-2-thione","An improved process for the preparation of 4,4-dimethyloxazolidine-2-thione ( 1 ), an auxiliary used in the synthesis of (3 S,4 S )-[( R )-1‘-(( tert -butyldimethylsilyl)oxy)ethyl]-4-[( R )-1-carboxyethyl]-2-azetidinone ( 2 ), a key intermediate for carbapenem synthesis is reported.",10.1021/op6002677,2007-04-03,0.6778490064264188
Journal of the American Chemical Society,Stereocontrolled Total Synthesis of (−)-Eudistomin C,"A stereocontrolled total synthesis of (-)-eudistomin C was accomplished in 18-step sequence with an overall yield of 7.7%. The synthesis features the diastereoselective Pictet-Spengler reaction of a tryptamine derivative and the Garner aldehyde catalyzed by Bronsted acids, and the unprecedented construction of the unusual oxathiazepine ring by intramolecular alkylation.",10.1021/ja055832h,2005-10-07,0.6778483089326176
European Journal of Organic Chemistry,An Efficient Approach to the Total Synthesis of Ammosamide B,"Abstract A new approach for the total synthesis of ammosamide B was realized. The strategy is based on an intermolecular Pd‐catalyzed N ‐arylation of 4‐chloro‐1‐methylindoline‐2,3‐dione ( 2 ), which enables construction of the key pyrroloquinoline skeleton precursor 6 within three steps in an overall yield of 80 %. The ammosamide B total synthesis is achieved in 12 simple transformations by starting from a commercially available starting material and proceeds with an overall yield of 23 %. Additionally, key precursor 6 represents an important intermediate in the synthesis of other pyrroloquinoline‐containing natural products.",10.1002/ejoc.201501560,2016-01-15,0.6777877996589321
Organic Process Research & Development,Scalable Synthesis of β-Lactamase Inhibitor QPX7728 by Sequential Nickel-Catalyzed Boron Insertion into a Benzofuran Substrate and Enantioselective Cyclopropanation of the Resulting Vinylboronate,"We report the scalable, high-yielding, and highly selective synthesis of the β-lactamase inhibitor QPX7728 featuring two key synthetic steps: nickel-catalyzed boron insertion of benzofuran 1 followed by enantioselective cyclopropanation of the resulting cyclic vinylboronate 2 . The identification of the key reagents (catalyst and chiral auxiliary) for both steps relied on the use of high-throughput experimentation. Further optimization allowed for the cost-effective and scalable production of QPX7728.",10.1021/acs.oprd.1c00285,2021-09-15,0.6777237846378199
Organic Letters,"Carbocyclization of Carbohydrates: Diastereoselective Synthesis of (+)-Gabosine F, (−)-Gabosine O, and (+)-4-<i>epi</i>-Gabosine O","Exploitation of silica gel/chloramine T mediated intramolecular nitrile oxide-alkene cycloaddition (INOC) of sugar-derived oximes to carbocycles furnished the first synthesis of gabosine F from l-arabinose in 12 steps with 23% overall yield, thereby confirming its absolute configuration. Similarly, efficient syntheses of gabosine O and 4-epi-gabosine O were accomplished from D-mannose in 9 and 11 steps with 41% and 38% overall yields, respectively, involving INOC, regioselective dehydration, and diastereoselective hydrogenation as the key steps.",10.1021/ol902071e,2009-10-05,0.6776517646552149
Synlett,Diastereocontrolled Synthesis of (-)-Codonopsinine,"An efficient process is described for the total synthesis of the alkaloid (-)-codonopsinine. The synthetic strategy is based on the diastereoselective hydrocyanation of a 2,3-dialkoxyaldehyde derived from l-threonine followed by a reductive alkylation of the nitrile function with a Grignard compound and sodium borohydride. The resulting aminotriol was then cyclized into the target molecule after selective mesylation.",10.1055/s-2003-36777,2003-01-01,0.6776190343598278
Tetrahedron,One-pot reductive-cyclization as key step for the synthesis of rutaecarpine alkaloids,,10.1016/j.tetlet.2007.11.094,2007-11-26,0.6776157518449495
Journal of Organic Chemistry,"Synthesis of α-Galactosyl Ceramide, a Potent Immunostimulatory Agent","Alpha-galactosyl ceramide has been identified to be a potent stimulatory agent for a novel immunological process, mediated by CD1 molecules. This paper describes a short and efficient synthesis of alpha-galactosyl ceramide. Starting from commercially available 2-deoxy galactose, a suitable sphingosine derivative was obtained in nine steps and 36% overall yield, which was subsequently glycosylated to give the target molecule. This flexible route will provide various glycolipids for further exploration of this interesting biological process.",10.1021/jo0201530,2002-05-10,0.6775989150394545
Organic Process Research & Development,Development of an Efficient Manufacturing Process for a Key Intermediate in the Synthesis of Edoxaban,"We report the development of a novel synthetic method to access a key intermediate in the synthesis of edoxaban. The main features of the new synthetic method are an improvement in the approach for the synthesis of a key chiral bromolactone, application of an interesting cyclization reaction utilizing neighboring group participation to construct a differentially protected 1,2- cis -diamine, and implementation of plug-flow reactor technology to enable the reaction of an unstable intermediate on multihundred kilogram scale. The overall yield for the preparation of edoxaban was significantly increased by implementing these changes and led to a more efficient and environmentally friendly manufacturing process.",10.1021/acs.oprd.8b00413,2019-02-20,0.6775736529500213
Organic Letters,Total Synthesis of Himandravine,"[reaction: see text] The first total synthesis of (+)-himandravine (1) is described, starting from (2S,6S)-cis-2-formyl-6-methyl-N-Boc-piperidine (8) in 11 linear steps and 17% overall yield. The key step involves a highly diastereoselective intramolecular Diels-Alder reaction of the key intermediate 5 that contains the entire latent carbon framework and functional group substitution of himandravine.",10.1021/ol010038w,2001-04-21,0.6775651086628576
Organic Process Research & Development,Scale-Up Synthesis of the Dopamine Uptake Inhibitor GBR-12909,"1-[2-[Bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine (GBR-12909) is a dopamine uptake inhibitor. The development of a robust process for the preparation of this compound in kilogram quantities is described. The primary aims of the development work were to eliminate chromatographic purifications, to minimize the use of environmentally unacceptable reagents, and to improve the overall yield of the three-step convergent process. These objectives were met, with significant improvements obtained in the key coupling reaction of N -(3-phenylpropyl)piperazine dihydrochloride salt with 1-[bis(4-fluorophenyl)methoxy]-2-chloroethane, which was previously low-yielding and lacking in reproducibility.",10.1021/op020211j,2002-07-18,0.6774904940507214
European Journal of Organic Chemistry,The Synthesis of (±)‐Oxyisocyclointegrin,"The total synthesis of oxyisocyclointegrin is described. The key steps in the synthesis included a Tsuji–Trost allyl migration to exclusively afford the corresponding monoallylated 1,3‐diketone and a photochemical initiated oxidative cyclization to forge the oxepine core.",10.1002/ejoc.201801751,2019-01-11,0.6773792860408326
Organic Process Research & Development,Practical Asymmetric Fluorination Approach to the Scalable Synthesis of New Fluoroaminothiazine BACE Inhibitors,"Here we report an optimized protocol for the asymmetric introduction of a fluorine atom into a quaternary center facilitated by d -proline, Selectfluor ®, and trifluoroethanol. The synthesis proceeds over four steps starting from a chiral amino alcohol precursor and provides the desired enantiomer with no erosion of chiral purity and good diastereoselectivity. The process optimization allowed diastereoselective preparation of the key intermediate on a multigram scale.",10.1021/acs.oprd.8b00069,2018-04-24,0.6773751428947299
Organic Process Research & Development,A Practical Synthesis of a PI3K Inhibitor under Noncryogenic Conditions via Functionalization of a Lithium Triarylmagnesiate Intermediate,We report a practical synthesis of PI3K inhibitor GDC-0941 . The synthesis was achieved using a convergent approach starting from a thienopyrimidine intermediate through a sequence of formylation and reductive amination followed by Suzuki-Miyaura cross-coupling. Metalation of the thienopyrimidine intermediate involving the intermediacy of triarylmagnesiates allowed formylation under noncryogenic conditions to produce the corresponding aldehyde. We also investigated aminoalkylation via a benzotriazolyl-piperazine substrate as an alternative to the reductive amination route. We evaluated both palladium and nickel catalyzed processes for the borylation and Suzuki-Miyaura cross-coupling. Final deprotection and salt formation afforded the API.,10.1021/op3002992,2012-12-16,0.67732695871264
Journal of Organic Chemistry,Halichondrin B:  Synthesis of the C(1)−C(15) Subunit,"A short and efficient synthesis of the C(1)-C(15) subunit of halichondrin B in its natural configuration is described. The polycyclic caged ketal 3, containing nine asymmetric centers, is prepared in 14 steps from alpha-D-glucoheptonic acid gamma-lactone (7). Key steps in the two similar routes described include EtMgBr-promoted pinacol ring expansions of hydroxy mesylates 23 and 34, intramolecular Michael additions of 29 and 37, and a one-pot, HF-induced conversion of 4 to 3involving in situ silyl ether cleavage, acetal hydrolysis, Michael addition, and caged ketal formation. Alternative protocols for carbinol inversion at C(11), one early and one late in the synthetic sequence, are also described.",10.1021/jo000140r,2000-06-01,0.6773226848283931
Synlett,A Concise Synthesis of Dunnianol,A short total synthesis of the neosesquilignan dunnianol which features a double Suzuki cross-coupling as a key step is described.,10.1055/s-0029-1219209,2010-01-19,0.677309459532627
Journal of the American Chemical Society,Titanium(II)-Mediated Cyclizations of (Silyloxy)enynes:  A Total Synthesis of (−)-7-Demethylpiericidin A<sub>1</sub>,A concise total synthesis of 7-demethylpiericidin A1 has been completed. The synthesis features a titanium(II)-mediated cyclization of a (silyloxy)enyne as the key step and proceeds in nine steps from tiglic aldehyde.,10.1021/ja057434k,2005-12-17,0.677251537192973
Synthesis,Total Synthesis of (-)-Pyrenophorol,"An efficient synthetic route has been developed for the synthesis of (-)-pyrenophorol employing Sharpless asymmetric epoxidation, olefin cross-metathesis, and intermolecular Mitsunobu cyclization.",10.1055/s-0031-1289703,2012-02-13,0.6772049068377899
Organic Letters,Total Synthesis of Ripostatin A,"The first total synthesis of the bacterial RNA-polymerase inhibitor ripostatin A (1) was achieved. The route utilizes a cyclic methyl acetal intermediate and a sequence of a double Stille cross-coupling reaction followed by a ring-closing metathesis for the construction of the macrolactone ring. Additionally, an unprecedented formation of the 4-methoxy substituted tetrahydropyrans was observed during the acid catalyzed acetalization of the β,δ-dihydroxyketone.",10.1021/ol302219x,2012-08-23,0.677202657410952
Tetrahedron,Reaction of unsymmetrical dienophiles with a key dienoid intermediate for aphidicolin synthesis,,10.1016/s0040-4039(00)98849-x,1985-01-01,0.6771923740571932
Organic Process Research & Development,Concise Process for Pyriftalid Synthesis by Introducing the Mercapto Group Directly from a Nitro Group,"A concise and efficient process for the synthesis of pyriftalid is described herein. The improved process features the direct introduction of the mercapto group by one-step substitution of a nitro group using sodium sulfide and elemental sulfur. A systematic study of the key step is also carried out in this article. Compared with previous routes, the optimized route is shorter and avoids a hazardous catalytic reduction and a subsequent diazotization reaction. Salt waste generated in workup is reduced as well. Pyriftalid is obtained in 68% overall yield and 99.88% purity in five steps with 3-nitrophthalic acid as the starting material.",10.1021/acs.oprd.1c00384,2022-01-21,0.677182311528179
Organic Process Research & Development,Development of Scalable Manufacturing Routes to AZD1981. Application of the Semmler–Wolff Aromatisation for Synthesis of the Indole-4-amide Core,"A safe and efficient synthesis of AZD1981 is described in which the indole 4-amide core is formed by a Semmler–Wolff aromatisation of a cyclohexenone oxime fused to a pyrrole ring. The substrate was obtained via Paal–Knorr pyrrole synthesis, followed by incorporation of the key 3-arylthio substituent by reaction with 4-chlorophenylsulfenyl chloride. In this manner, the 1,2,3,4-substitution pattern of the AZD1981 core was regiospecifically established in a concise and efficient telescoped sequence. Accordingly, AZD1981 was obtained in 40% overall yield in six chemical steps, with two isolated crystalline intermediates.",10.1021/op300173z,2012-10-18,0.6771796285036898
Organic Letters,A Practical Synthetic Route to Enantiopure 6-Substituted <i>cis</i>-Decahydroquinolines,"Starting from 4-substituted cyclohexanones, a practical synthetic route to enantiopure 6-substituted cis-decahydroquinolines has been developed, the key steps being a stereoselective cyclocondensation of an unsaturated δ-keto ester derivative with (R)-phenylglycinol and the stereoselective hydrogenation of the resulting tricyclic oxazoloquinolone lactams.",10.1021/ol2030058,2011-12-01,0.6771693528535211
Organic Letters,Synthesis of (±)-Phloeodictine A1,"The antitumor antibiotic phloeodictine A1 (2) has been synthesized by a convergent seven-step route in 8% overall yield. The key step was the Eguchi aza-Wittig reaction of 6 to give 13 followed by a retro Diels-Alder reaction to liberate 5. Addition of 11-dodecenylmagnesium bromide to 5 to give 4b, alkylation with 18b, and deprotection completed the first synthesis of 2.",10.1021/ol034042e,2003-02-07,0.6771201022040062
Organic Process Research & Development,Route Development and Multikilogram GMP Delivery of a Somatostatin Receptor Antagonist,"Route development and demonstration on multikilogram scale for the first GMP delivery of MK-4256 are described. Key aspects of the convergent route include a regioselective green iodination, one-pot oxadiazole synthesis, and an efficient ketone Pictet–Spengler reaction with diastereomeric upgrade via crystallization to afford 6 kg of API. A recycle procedure augmented the yield of desired diastereomer in the Pictet–Spengler reaction from a mixture of diastereomers heavily enriched in the undesired diastereomer.",10.1021/op300128c,2012-08-01,0.6771001839074224
Angewandte Chemie International Edition,A Sequential Two‐Component Etherification/Oxa‐Conjugate Addition Reaction: Asymmetric Synthesis of (+)‐Leucascandrolide A Macrolactone,"A smooth operator: The asymmetric synthesis of the macrolactone of (+)-leucascandrolide A (see structure) has been accomplished through a convergent route (longest linear sequence of 14 steps) in 20 % overall yield. The assembly of the 1,5-bis(tetrahydropyran) core in a single operation provides the most concise synthetic approach developed to date.",10.1002/anie.200801357,2008-06-13,0.6770988307625655
Organic Letters,Efficient Asymmetric Synthesis of (+)-SCH 351448,"An efficient and stereocontrolled total synthesis of (+)-SCH 351448, a novel activator of low-density lipoprotein receptor promoter, has been achieved with a longest linear sequence of 21 steps. Key steps include applications of the recently developed asymmetric allyl- and crotylsilane reagents and a new protodesilylative version of the tandem silylformylation/allylsilylation reaction, which provides an efficient synthesis of 1,5-syn-diols. [reaction: see text]",10.1021/ol0515006,2005-07-20,0.6770789959791166
Organic Process Research & Development,"Development of a Practical and Efficient Synthesis of CP-945,598-01, a CB<sub>1</sub> Antagonist for the Treatment of Obesity","Development of an efficient bond-forming sequence and optimization of reaction conditions are described for the synthesis of CP-945,598-01 ( 1 ·HCl), a CB 1 antagonist in clinical studies for the treatment of obesity. Reordering of the bond-forming sequence provided a more efficient synthesis and avoided the use of phosphorous oxychloride. A telescoped reaction sequence ( 4 → 9 ) was developed to avoid a problematic isolation. Product isolations were developed so as to provide efficient throughput by minimizing solvent volumes and avoiding slow filtrations.",10.1021/op800255j,2008-12-22,0.6770593588249693
Journal of the American Chemical Society,"Practical Gram-Scale Synthesis of Iboxamycin, a Potent Antibiotic Candidate","A gram-scale synthesis of iboxamycin, an antibiotic candidate bearing a fused bicyclic amino acid residue, is presented. A pivotal transformation in the route involves an intramolecular hydrosilylation–oxidation sequence to set the ring-fusion stereocenters of the bicyclic scaffold. Other notable features of the synthesis include a high-yielding, highly diastereoselective alkylation of a pseudoephenamine amide, a convergent sp 3 –sp 2 Negishi coupling, and a one-pot transacetalization–reduction reaction to form the target compound’s oxepane ring. Implementation of this synthetic strategy has provided ample quantities of iboxamycin to allow for its in vivo profiling in murine models of infection.",10.1021/jacs.1c03529,2021-07-15,0.6770475122066953
Organic Letters,"Synthesis of Grazoprevir, a Potent NS3/4a Protease Inhibitor for the Treatment of Hepatitis C Virus","An efficient synthesis of grazoprevir is reported. Starting from four readily available building blocks, grazoprevir is prepared in 51% overall yield and >99.9% purity for pharmaceutical use.",10.1021/acs.orglett.8b03173,2018-11-02,0.6770457471169313
Organic Letters,"Scalable Synthesis of a Dual TLR7/8 Agonist via Highly Selective <i>N</i> 2-Alkylation of 1 <i>H</i> -Pyrazolo[4,3- <i>d</i> ]pyrimidine","We report a scalable synthesis of a potent dual TLR7/8 agonist featuring a pyrazolopyrimidine core. An acid-mediated selective N 2-alkylation of 1 H -pyrazolo[4,3- d ]pyrimidine with free benzyl alcohol furnishes the N 2-alkylated product in 72% yield with high regioselectivity (14:1 N 2/ N 1). Subsequent copper-catalyzed amination with aqueous ammonia installs the C 5 amino group in 70% yield, avoiding azides or complex ammonia surrogates. The convergent sequence proceeds in 34% overall yield from readily available materials and is amenable to kilogram-scale production.",10.1021/acs.orglett.5c04092,2025-10-31,0.6770415011311057
Journal of Organic Chemistry,Synthesis of HIV-Maturation Inhibitor BMS-955176 from Betulin by an Enabling Oxidation Strategy,"A concise and scalable second generation synthesis of HIV maturation inhibitor BMS-955176 is described. The synthesis is framed by an oxidation strategy highlighted by a Cu I mediated aerobic oxidation of betulin, a highly selective PIFA mediated dehydrogenation of an oxime, and a subsequent Lossen rearrangement which occurs through a unique reaction mechanism for the installation of the C17 amino functionality. The synthetic route proceeds in 7 steps with 47% overall yield and begins from the abundant and inexpensive natural product betulin.",10.1021/acs.joc.7b00438,2017-04-13,0.676978694579553
Organic Letters,A Short Diastereoselective Total Synthesis of (±)-Vibralactone,"A total synthesis of the (±)-vibralactone has been achieved in 11 steps and 16% overall yield from malonic acid. Key steps include a highly diastereoselective allylation of an α-formyl ester containing an all carbon α-quaternary center, a Pd-catalyzed deallylative β-lactonization, and an aldehyde-selective Wacker oxidation of a terminal alkene.",10.1021/acs.orglett.6b03007,2016-10-31,0.6769420850621368
Angewandte Chemie International Edition,"Organocatalytic and Scalable Synthesis of the Anti‐Influenza Drugs Zanamivir, Laninamivir, and CS‐8958","Zanamivir, laninamivir, and CS-8958 are three neuraminidase inhibitors that have been clinically used to combat influenza. We report herein a novel organocatalytic route for preparing these agents. Only 13 steps are needed for the assembly of zanamivir and laninamivir from inexpensive D-araboascorbic acid by this synthetic route, which relies heavily on a thiourea-catalyzed enantioselective Michael addition of acetone to tert-butyl (2-nitrovinyl)carbamate and an anti-selective Henry reaction of the resulting Michael adduct with an aldehyde prepared from D-araboascorbic acid. The synthetic procedures are scalable, as evident from the preparation of more than 3.5 g of zanamivir.",10.1002/anie.201408138,2014-10-14,0.6767843714507905
Tetrahedron,Enantioselective Total Synthetic Route to (+)-Aphidicolin,,10.1016/00404-0399(50)1044i-,1995-07-24,0.6767505467435505
Tetrahedron,Enantioselective total synthetic route to (+)-aphidicolin,,10.1016/0040-4039(95)01044-i,1995-07-01,0.6767505467435505
Journal of Organic Chemistry,Weinreb Amide Approach to the Practical Synthesis of a Key Remdesivir Intermediate,"Currently, remdesivir is the first and only FDA-approved antiviral drug for COVID-19 treatment. Adequate supplies of remdesivir are highly warranted to cope with this global public health crisis. Herein, we report a Weinreb amide approach for preparing the key intermediate of remdesivir in the glycosylation step where overaddition side reactions are eliminated. Starting from 2,3,5-tri- O -benzyl- d -ribonolactone, the preferred route consisting of three sequential steps (Weinreb amidation, O -TMS protection, and Grignard addition) enables a high-yield (65%) synthesis of this intermediate at a kilogram scale. In particular, the undesirable PhMgCl used in previous methods was successfully replaced by MeMgBr. This approach proved to be suitable for the scalable production of the key remdesivir intermediate.",10.1021/acs.joc.0c02986,2021-03-18,0.6767373643970566
Tetrahedron,A short efficient synthesis of ambraketal (four steps) and epiambraketal (five steps) from Sclareol,,10.1016/0040-4039(94)88171-5,1994-01-01,0.6767348900163127
Journal of the American Chemical Society,Asymmetric Synthesis of (+)-Polyanthellin A,"A concise and convergent route to (+)-polyanthellin A is presented. This synthesis features a diastereoselective cyclopropane/aldehyde [3+2] cycloaddition to install the hydroisobenzofuran core. The use of MADNTf(2) as a potent, bulky Lewis acid was essential to allow a labile beta-silyloxy aldehyde to be used in the cycloaddition. Other key steps include a ring-closing metathesis and a selective olefin oxidation.",10.1021/ja904136q,2009-07-14,0.6767205969083496
Angewandte Chemie International Edition,Enantioselective Total Synthesis of the Osteoclastogenesis Inhibitor (+)‐Symbioimine,"No bones about it: The first enantioselective total synthesis of the osteoclastogenesis inhibitor (+)-symbioimine (1) has been achieved. The synthesis features a convergent enol silane addition to a dimethyl acetal and a key, possibly biomimetic, intramolecular Diels–Alder reaction promoted by a dihydropyridinium ion to build four of the five requisite stereocenters in one step.",10.1002/anie.200605160,2007-03-15,0.6766366087766043
Organic Letters,Total Synthesis of the Phenolic Steroid Myrmenaphthol A,"Myrmenaphthol A is a structurally unique phenolic steroid with a naphthyl AB-ring system and an unusual C2 hydroxy group. Herein, we report the first total synthesis of this natural product in 10 steps from inexpensive, commercially available sitolactone. Key features of the synthesis include a Baran decarboxylative coupling and a Friedel-Crafts cyclization/olefin isomerization/aromatization cascade that rapidly assembled the tetracyclic core framework. This synthetic strategy is expected to be readily amenable to the synthesis of other phenolic steroids.",10.1021/acs.orglett.2c02910,2022-10-03,0.6765959892245541
Synthesis,A Formal Total Synthesis of Fostriecin by a Convergent Approach,"A formal total synthesis of fostriecin has been accomplished in 20 steps. Our method features the derivation of two of the four chiral centers from commercial diethyl d-(+)-malate. The key steps involve the Julia-Kocienski olefination, the Sharpless asymmetric dihydroxylation, and the Stille coupling.",10.1055/s-0030-1258187,2010-07-16,0.6765779129152574
Synthesis,Novel Synthesis of Arylethynyl Heterocycles,"A new and easy synthesis of 2-arylethynylindole and 2-arylethynyl-pyrrole is described. Ndeprotection and subsequent base-catalyzed elimination of N-tosylheteroaryl benzyl ketones are the key steps of the process. Key words: acetylenes, indole,",10.1055/s-2007-966041,2007-05-02,0.6765497218501186
Organic Process Research & Development,A Convenient One-Step Synthesis of Methyl 2-Benzamidomethyl-3-oxobutanoate,"A convenient one-step process for the preparation of methyl 2-benzamidomethyl-3-oxobutanoate ( 1 ), a raw material used in the synthesis of (2 R,3 R )-3-(( R )-1-( tert -butyldimethylsilyloxy)ethyl)-2,3-dimethyl-4-oxoazetidin-2-yl acetate ( 2 ), a key intermediate for carbapenem synthesis is reported. The process is carried out under mild reaction conditions and is amenable to large-scale synthesis.",10.1021/op800313t,2009-02-26,0.6765349441063538
Organic Process Research & Development,Development of a Streamlined Manufacturing Process for the Highly Substituted Quinazoline Core Present in KRAS G12C Inhibitor <i>Divarasib</i>,"A streamlined process for the synthesis of a highly functionalized quinazoline that enabled late-stage preparation of KRAS G12C inhibitor divarasib is presented herein. The highlights of the synthesis are a telescoped four-step preparation of the key 2-amino-4-bromo-3-fluorobenzonitrile intermediate, a critical aromatic chlorination using NCS and catalytic HCl, a cyclization to a quinazoline dione employing CO 2 and DBU, and a DABCO−MsOH-catalyzed Halex reaction to form target quinazoline fluoride 2 . In the chlorination step, we encountered an unusual halogen scrambling, resulting in critical 4,5-dichloro and 4,5-dibromo impurities that needed to be controlled down to low levels due to minimal purging power in downstream chemistry. The manufacturing process was demonstrated by the preparation of >500 kg of quinazoline 2 in 39% overall yield and 99.5 area % HPLC purity over nine chemical steps and five isolations.",10.1021/acs.oprd.3c00351,2024-01-09,0.676381641116198
Journal of Organic Chemistry,Total Synthesis of (+)-Hyacinthacine A<sub>2</sub>Based on SmI<sub>2</sub>-Induced Nitrone Umpolung,"[reaction: see text] A concise total synthesis of (+)-hyacinthacine A(2), a polyhydroxylated pyrrolizidine alkaloid, is described using our recently discovered inversion of the C-N bond polarity in nitrones. In the key step, the diastereoselective reductive coupling of a L-xylose-derived cyclic nitrone with ethyl acrylate allowed the assembly of the bicyclic core of the target molecule, by way of a tandem formation of the C-C and C-N bonds. The method opens a novel, short, and general route for the synthesis of other pyrrolizidine alkaloids.",10.1021/jo048237r,2005-01-19,0.6763646365060799
Tetrahedron,Palladium catalyzed reductive cyclization reaction in alkaloid synthesis — an enantioselective total synthetic route to (+)-pumiliotoxin C,,10.1016/0040-4039(96)00861-1,1996-06-01,0.6763479901341732
Organic Process Research & Development,Development and Kilogram-Scale Synthesis of a D<sub>2</sub>/5-HT<sub>2A</sub> Receptor Dual Antagonist (±)-SIPI 6360,"The kilogram-scale synthesis of a D 2 /5-HT 2A receptor dual antagonist (±)-SIPI 6360 was developed as an alternative treatment for schizophrenia. Specifically, three conditions were modified and optimized, including the Vilsmeier conditions, to prepare quinoline 3 . In addition, the palladium-catalyzed hydrogenation was modified to synthesize dihydroquinolin-2(1 H )-one 5, and the reduction of β-chloroamide was altered to form 3-chloropropanamine 8 . Ultimately these improvements led to the preparation of a 1.5 kg of (±)-SIPI 6360 batch in eight steps with an overall yield of 34% and purity of 99.8%.",10.1021/acs.oprd.6b00220,2016-08-24,0.676330602621241
Journal of Organic Chemistry,The First Synthesis of the Pentacyclic Pyridoacridine Marine Alkaloids: Arnoamines A and B,"The synthesis of the marine pyridoacridine alkaloids arnoamines A and B has been accomplished in six and seven steps from 4-chloro-8-methoxy-5-nitroquinoline in 13% and 4% overall yield, respectively.",10.1021/jo000011a,2000-08-15,0.6762599878196204
Tetrahedron,A novel synthetic route to a process-related impurity of alectinib,,10.1016/j.tetlet.2025.155869,2025-10-21,0.6762540821334266
Synlett,Chiral Synthesis of the C<sub>3-13</sub> Segment of Epothilone A,All articles of this category Synthesis of the title compound using inexpensive geraniol as starting material in 13 steps and in 10.6% overall yield is described. epothilone A - synthesis - geraniol - acetylide reaction - aldol condensation,10.1055/s-1997-1076,2000-12-31,0.6762368250240551
Organic Letters,A Total Synthesis of (−)-Hamigeran B and (−)-4-Bromohamigeran B,"A concise synthesis of (−)-hamigeran B and (−)-4-bromohamigeran B is presented. The key reactions include a Suzuki coupling of enol triflate 15 with arylboronic ester for efficient synthesis of the densely 1,2,3-trisubstituted cyclopentene 23, a coordination-controlled intramolecular Friedel–Crafts cyclization of free phenol 13 for highly regioselective construction of tricyclic core 12, and a LiOH/O 2 -promoted hydrolysis and concomitant aerobic oxidation of 31 for atom- and step-economic accessing of diketone 32 . The application of these key transformations allowed for a rapid and efficient synthesis of (−)-hamigeran B and (−)-4-bromohamigeran B in 13 steps from the readily available chiral material 18 .",10.1021/acs.orglett.8b01490,2018-06-06,0.6762304340457872
Organic Process Research & Development,An Improved and Scalable Process for Obtaining Pure Betaxolol Hydrochloride on an Industrial Scale,"This study details the development of a novel and improved process for the multikilogram scale synthesis of Betaxolol hydrochloride, a β-blocker medication. The condensation of cyclopropyl methyl bromide (CPMBr) with a phenylethanol intermediate to produce an oxirane intermediate was a vital step in the synthesis. The reaction with isopropyl amine then produced a racemate of the Betaxolol base. The purification of crude Betaxolol base via sorbate salt formation and its crystallization enabled the desired quality of the Betaxolol base. It aided in achieving the desired quality in accordance with International Conference on Harmonization (ICH) guidelines and specification requirements outlined in the European Pharmacopoeia (EP) monograph. This improved process eliminated the need for column chromatography. There were only a few process impurities in the intermediates. The new approach described here is more efficient, with an overall yield of 37% with a quality of 99.8%, and sustainable than earlier processes reported in the literature, and it has the potential to become the commercial manufacturing route. This process was used to produce Betaxolol hydrochloride on a 20 kg scale without column chromatographic purification from para-hydroxy phenyl ethanol as the starting material and submitted to a Certificate of Suitability (CoS) with a regulatory authority.",10.1021/acs.oprd.3c00449,2024-07-03,0.6762135996028011
Organic Process Research & Development,Development of an Efficient Synthesis of the Pyrrolquinolone PHA-529311,"An efficient synthesis of N -(4-chlorobenzyl)-2-(2-hydroxyethyl)-8-(morpholin-4-ylmethyl)-6-oxo-6H-pyrrol[3.2.1- ij ]quinoline-5-carboxamide ( 5 ) was developed. The route was chosen due to its reasonable length (seven steps), solubility of intermediates, and capabilities of the pilot and production facilities. The critical transformations in this route were the selective iodination of an aniline, formation of the quinolone, and Sonogashira coupling/pyrrole formation. In addition, removal of residual palladium and copper from the penultimate and final products, which was of lower concern during the discovery phase of development, became a difficult process chemistry issue on scale-up.",10.1021/op050251y,2006-04-18,0.6761920496142275
Tetrahedron,A novel route for the synthesis of highly congested aryl-tethered 2-aminobenzylamines through ring transformation of 2-pyranones,,10.1016/j.tetlet.2007.03.038,2007-03-13,0.6761869941308185
Organic Letters,A Short Asymmetric Route to the Bromophycolide A and D Skeleton,"An asymmetric synthesis of the bromophycolide D ring system has been achieved in seven steps from a known geranylgeranylated benzoate, via bromonium-promoted transannular cyclization of a macrocyclic intermediate.",10.1021/ol200099n,2011-02-10,0.6761632082990747
Journal of the American Chemical Society,Nature-Inspired Total Synthesis of (−)-Fusarisetin A,"A concise, protecting group-free total synthesis of (-)-fusarisetin A (1) was efficiently achieved in nine steps from commercially available (S)-(-)-citronellal. The synthetic approach was inspired by our proposed biosynthesis of 1. Key transformations of our strategy include a facile construction of the decalin moiety that is produced via a stereoselective IMDA reaction and a one-pot TEMPO-induced radical cyclization/aminolysis that forms the C ring of 1. Our route is amenable to analogue synthesis for biological evaluation.",10.1021/ja300807e,2012-03-05,0.6761417097331031
Journal of Organic Chemistry,Advanced Synthetic Strategies toward Ginkgolide Diterpenoids: Total Synthesis of (±)-Ginkgolide C and Formal Syntheses of (±)-Ginkgolides A and B,"Ginkgolides are highly oxygenated diterpenes isolated from Ginkgo biloba that exhibit potent anti-inflammatory and neuroprotective properties. Their compact hexacyclic architecture─featuring multiple contiguous stereocenters, a spirocyclic core, and a rare tert -butyl group─presents a formidable challenge in synthetic organic chemistry. Herein, we report the first total synthesis of ginkgolide C ( 3 ), the most structurally complex member of this family, completed in 26 steps from commercially available materials. The synthesis is guided by a functional group-driven strategy that enables the convergent construction of the polycyclic core through key diastereoselective carbon–carbon bond formations, selective oxidations, and late-stage epoxide-opening lactonizations. In parallel, the formal syntheses of ginkgolides A ( 1 ) and B ( 2 ) were accomplished via interception of a late-stage intermediate in 17 steps, the shortest route to these targets reported to date. This work provides a unified synthetic platform for accessing the ginkgolide family and offers new opportunities for the synthesis and biological evaluation of related analogues.",10.1021/acs.joc.5c01012,2025-06-25,0.6761139352687662
Organic Letters,(−)-Lytophilippine A: Synthesis of a C1−C18 Building Block,"The convergent enantioselective synthesis of a protected C1-C18 building block for the total synthesis of (-)-lytophilippine A was achieved. A catalytic asymmetric Gosteli-Claisen rearrangement and an Evans aldol reaction served as key C/C-connecting transformations during the assembling of the C1-C7 subunit (10 steps from 4, 29%). The synthesis of the C8-C18 segment was achieved utilizing d-galactose as inexpensive ex-chiral-pool starting material (15 steps, 15%). The merger of the subunits was accomplished by a remarkably efficient sequence consisting of esterification and ring-closing metathesis (five steps, 56%).",10.1021/ol1023008,2010-10-25,0.6761092051784897
Organic Letters,"Enantioselective Synthesis of Nicotinic Receptor Probe 7,8-Difluoro-1,2,3,4,5,6- hexahydro-1,5-methano-3-benzazocine","[Structure: see text] The development of a concise enantioselective synthesis of nicotinic alkaloid 1 is presented. The route features the synthesis and use of a ""stable"" aliphatic triflate 21 in an alkylation step to generate Heck precursor 24 and an enantioselective cyclization to establish a compound with the key [3.2.1]-bicyclic core, 29.",10.1021/ol0623062,2006-11-29,0.6761043004388074
Organic Process Research & Development,Process Development to Synthesize SGD-11275 Utilizing a Pd-Catalyzed Acetamide Arylation and Gallium-Mediated Friedel–Crafts Acylation,"An improved synthesis of SGD-11275 was developed to address inefficiencies in cost, time, and safety associated with the previous supply route. The new route features a Buchwald-Hartwig amination with acetamide optimized by high-throughput experimentation as well as a GaCl 3 -mediated Friedel–Crafts acylation. Subsequent amide hydrolysis was demonstrated from the isolated Friedel–Crafts product and as a through-process with equal effectiveness. The new route reduced the commercial synthesis by three steps and increased the overall yield by 18.6%.",10.1021/acs.oprd.4c00375,2024-11-26,0.6760408651331786
Organic Process Research & Development,Development of a Supply Route for the Synthesis of an iNOS Inhibitor: Complications of the Key S<sub>N</sub>2 Reaction,"The original medicinal chemistry synthesis of an iNOS inhibitor presented several challenges that had to be overcome in order to constitute a supply route suitable for operation on a multikilo scale. The key step in the synthesis is an S N 2 reaction that assembles the chiral carbon framework, but this reaction proved far more complex than we anticipated. Significant improvements were made to all stages. The modified route performed well over two pilot-plant campaigns and delivered over 250 kg of the active pharmaceutical ingredient (API).",10.1021/op900108b,2009-07-02,0.6760353886777497
Organic Process Research & Development,"A Practical Synthesis of 2-Arylamino-6-alkylaminopurines from 2,6-Dichloropurine","A practical synthesis of N -[4-(6-cyclobutylamino- 9H -purin-2-ylamino)-phenyl]- N -methyl acetamide (QAB205, 5a ), an antiasthmatic agent, is described from 2,6-dichloropurine ( 1 ) by base-assisted substitution of the 6-chloro substituent with cyclobutylamine ( 2a ) followed by a new trimethylsilyl chloride-catalyzed displacement of the 2-chloro group in intermediate 6-cycbutylamino-2-chloropurine ( 3a ) with an aromatic amine. Both steps can also be carried out in one pot without isolating the intermediate 6-cyclobutylamino-2-chloropurine ( 3a ). The general synthetic utility of this route is demonstrated by synthesizing several 2-arylamino-6-alkylaminopurines ( 5 ).",10.1021/op060053m,2006-06-02,0.6760331052885392
Journal of Organic Chemistry,Enantioselective Total Synthesis of (−)-Limaspermidine and Formal Synthesis of (−)-1-Acetylaspidoalbidine,Evolution of the synthetic strategy that culminated in the first asymmetric total synthesis of the Aspidosperma alkaloid limaspermidine is described. The successful enantioselective route to (-)-limaspermidine proceeds in 10 steps and with the isolation of only six intermediates using a Pd-catalyzed enantioselective decarboxylative allylation we have recently developed. This first enantioselective synthesis of (-)-limaspermidine establishes unambiguously its absolute configuration and allows the first asymmetric formal total synthesis of the Aspidoalbine alkaloid (-)-1-acetylaspidoalbidine.,10.1021/jo402004f,2013-10-16,0.6760240239106631
European Journal of Organic Chemistry,"Two Synthesis Approaches of the 2<i>H</i>‐Tetrahydro‐4,6‐dioxo‐1,2‐oxazine Ring System of Alchivemycins A and B","Abstract The 2 H ‐tetrahydro‐4,6‐dioxo‐1,2‐oxazine (TDO) ring, a rare structural motif embedded in the molecular architecture of alchivemycins, is synthesized from 2,2,6‐trimethyl‐4 H ‐1,3‐dioxin‐4‐one via two routes. Both routes involve the intramolecular trapping of an acylketene intermediate by an internal hydroxy group to form the TDO ring as a key step. The first synthesis was achieved in 29 % overall yield from the starting material by a four‐step sequence featuring a DMAP−CaCl 2 ‐mediated O‐ to C‐acyl migration reaction to install an acyl group at the C5 position of the TDO ring. The second synthesis was completed in 8 % overall yield from the same starting material as the first one through five steps by exploiting a photo‐induced double bromination reaction.",10.1002/ejoc.202301006,2023-12-20,0.6759833652738996
Organic Letters,"Gram-Scale, Seven-Step Total Synthesis of (−)-Colchicine","Herein we report a streamlined, gram-scale total synthesis of (-)-colchicine that takes only 7 easy steps, with an overall yield of 27-36%. To warrant the synthetic efficiency and practicality of (-)-colchicine, we tactically utilized a modified version of a powerful Ir-catalyzed amidation reported by Carreira to install the key chiral C-7 acetamido group, Suzuki and biomimetic phenol oxidative coupling, and Banwell-inspired cyclopropane ring cleavage to construct (-)-colchicine precisely and rapidly. Remarkably, a described strategy also can shorten the synthesis of allocolchicinoid to 4 steps.",10.1021/acs.orglett.1c00638,2021-03-18,0.6759789305687905
Organic Process Research & Development,"Development of a Commercial Manufacturing Process for Vepdegestrant, an Orally Bioavailable PROTAC Estrogen Receptor Degrader for the Treatment of Breast Cancer","A commercial process for vepdegestrant ( 1 ), the most advanced PROTAC protein degrader in human clinical trials, has been developed to support clinical and commercial needs. The process features an efficient convergent synthetic strategy through the final reductive amination of two advanced chiral intermediates, as well as several highly efficient telescoped processes and robust crystallization for purity control. The final commercial process of vepdegestrant ( 1 ) consists of seven proposed regulatory GMP steps with five isolations in an overall yield of 29%.",10.1021/acs.oprd.4c00362,2024-11-05,0.6759223529350615
Journal of Organic Chemistry,Synthesis of (+)-Casuarine,"The first synthesis of (+)-casuarine ((+)-6), a pentahydroxy pyrrolizidine alkaloid of the alexine/australine subclass, is described. The key step is a tandem [4 + 2]/[3 + 2] nitroalkene cycloaddition involving nitrobenzoate 13, chiral vinyl ether 16c, and vinyl silane 10, which establishes five of the six stereocenters present in this potent glycosidase inhibitor. The completion of the synthesis requires only four additional steps to deliver the final product in 20% overall yield.",10.1021/jo991680v,2000-04-21,0.6759142857395424
Angewandte Chemie International Edition,Total Synthesis of the Tiacumicin B (Lipiarmycin A3/Fidaxomicin) Aglycone,"Tiacumicin B (lipiarmycin A3, fidaxomicin) is an atypical macrolide antibiotic which is used for the treatment of Clostridium difficile infections. Tiacumicin B is also a potent inhibitor of Mycobacterium tuberculosis, but due to its limited oral bioavailability is unsuitable for systemic therapy. To provide a basis for structure-activity studies that might eventually lead to improved variants of tiacumicin B, we have developed an efficient approach to the synthesis of the tiacumicin B aglycone. The synthesis features a high-yielding intramolecular Suzuki cross-coupling reaction to effect macrocyclic ring closure. Key steps in the synthesis of the macrocyclization precursor were a highly selective, one-pot Corey-Peterson olefination and an ene-diene cross-metathesis reaction. Depending on the reaction conditions, the final deprotection delivered either the fully deprotected tiacumicin B aglycone or partially protected versions thereof.",10.1002/anie.201409510,2014-12-15,0.6758905188438725
Organic Process Research & Development,A Convergent Synthesis of HPK1 Inhibitor GNE-6893 via Palladium-Catalyzed Functionalization of a Tetrasubstituted Isoquinoline,"A scalable convergent synthesis of GNE-6893 ( 1 ) involving Pd-catalyzed Suzuki–Miyaura cross-coupling and C–N coupling as key steps is reported. The production of the final active pharmaceutical ingredient (API) was achieved in 33% overall yield and 98 A% HPLC purity by a one-pot process of global deprotection, pH adjustment, crystallization, and isolation. Green chemistry practices were implemented in the process development of GNE-6893 ( 1 ) by utilizing a biocatalytic resolution to produce (3 R,4 S )-4-methyltetrahydrofuran-3-ol and replacing toxic triphosgene with a safer alternative, disuccinimidyl carbonate (DSC), to construct the carbamate penultimate intermediate to API.",10.1021/acs.oprd.2c00384,2023-02-27,0.6758902171885889
Organic Process Research & Development,Development of a Manufacturing Process for Zatosetron Maleate,"Zatosetron maleate is a potent, selective 5-hydroxytryptamine receptor antagonist. In anticipation of commercialization, a manufacturing synthesis of zatosetron from tropinone and 5-chlorosalicylic acid was developed. Development efforts focused on addressing several key issues including the supply and quality of the critical raw material tropinone, improvements in the stereoselective formation of 3- endo -tropanamine, and the compatibility with existing manufacturing capabilities of process requirements for the Claisen rearrangement used to produce a crucial benzofuran intermediate. The results of these studies and an improved route to zatosetron maleate are described.",10.1021/op970101q,1997-05-01,0.6758814588783051
Organic Letters,A Concise Total Synthesis of the Lichen Macrolide (+)-Aspicilin,The total synthesis of the polyhydroxylated macrolide (+)-aspicilin 5 is described using as a key step a highly diastereoselective allylation of aldehyde 6 with the uniquely functionalized allylstannane 1. (+)-Aspicilin is obtained in 18 steps and 10% overall yield. [structure: see text],10.1021/ol0620287,2006-09-30,0.6758624850268536
Synthesis,Technical Scale Synthesis of a New and Highly Potent Thrombin Inhibitor,"In this account, we describe the development of an efficient and convergent process for the peptidomimetic thrombin inhibitor 1 on production plant scale. Starting from nicotinonitrile (13), (2S,4R)-1-(tert-butoxycarbonyl)-4-hydroxy-2-pyrrolidinecarboxylic acid (5) and (2R)-2-amino-3-cyclohexylpropanoic acid (29) compound 1 was obtained in 16 chemical steps. New methods had been developed for the preparation of the key intermediate dehydroproline 22 and the transformation of nitriles into amidines. The thrombin inhibitor 1 was isolated by special techniques (nanofiltration and spray drying). Almost all salts of 1 are amorphous, however, a crystalline complex was obtained with 1,2-benzisothiazol-3(2H)-one 1,1-dioxide (Saccharin®).",10.1055/s-2004-831200,2004-01-01,0.6758212302770157
Journal of Organic Chemistry,Synthesis of Notoamide J: A Potentially Pivotal Intermediate in the Biosynthesis of Several Prenylated Indole Alkaloids,"An efficient total synthesis of notoamide J, a new prenylated indole alkaloid and potential biosynthetic precursor, is described herein. Starting from L-proline and a substituted tryptophan derivative, this synthesis also employs an oxidation and pinacol rearrangement for the formation of the oxindole in the final step.",10.1021/jo100332c,2010-04-01,0.6758159752496288
Organic Process Research & Development,"An Efficient Synthesis of a Key Intermediate for the Biologically Active Vitamin D Analogue, Seocalcitol","In the key synthetic step in the manufacture of the key intermediate for the biologically active vitamin D analogue, seocalcitol, a more practical and attractive procedure is achieved using the commercially available EtMgBr and CeCl 3, resulting in 79% yield. The key intermediate is synthesised from vitamin D 2 in 10 steps with only three isolations, giving 21% overall yield.",10.1021/op030037e,2003-12-10,0.6757879696980365
Tetrahedron,Asymmetric Heck cyclization route to indolizidine and azaazulene alkaloids: synthesis of (+)-5-epiindolizidine 167B and indolizidine 223AB,,10.1016/s0040-4039(01)01361-2,2001-09-01,0.6757845291995309
Journal of Organic Chemistry,Preparation of a Key Intermediate En Route to the Anti-HIV Drug Lenacapavir,"A very efficient four-step synthesis of the main fragment of Gilead's anti-HIV drug lenacapavir is described. The route showcases a 1,2-addition to an intermediate aldehyde using an organozinc halide derived from a commercially available difluorobenzyl Grignard reagent. This sets the stage for the oxidation of the resulting secondary alcohol to the desired ketone, which relies solely on catalytic amounts of TEMPO together with NaClO as the terminal oxidant, affording the targeted ketone in 67% overall yield.",10.1021/acs.joc.3c02855,2024-03-06,0.6757807035728413
Organic Process Research & Development,A Scalable Synthesis of a Hydroxamic Acid LpxC Inhibitor,"A short and scalable synthesis of chiral hydroxamic acid 1, a LpxC inhibitor, is described. This work discloses a novel diastereoselective addition of 2-nitropropane-generated lithium salt to tert -butanesulfinimine. Moreover, the impurity profiles of reactions giving oily products and practical means of purifying these products are discussed in detail.",10.1021/op300163n,2012-07-24,0.6757283429704926
Organic Process Research & Development,A Manufacturing Process to an Intermediate in the Synthesis of Acalabrutinib,"Optimization and application of the reported synthesis of (3-chloropyrazin-2-yl)methanamine 3 have provided a high yielding, fully telescoped procedure to key intermediate 5 in the synthesis of acalabrutinib.",10.1021/acs.oprd.8b00287,2018-10-01,0.6756585675408286
Tetrahedron,"The stereoselective synthesis of 4-formyltrinem, a key intermediate for novel trinems",,10.1016/s0040-4039(97)00665-5,1997-05-01,0.6756480630191035
Journal of Organic Chemistry,Efficient Asymmetric Synthesis of Novel Gastrin Receptor Antagonist AG-041R via Highly Stereoselective Alkylation of Oxindole Enolates,"An efficient method for asymmetric synthesis of the potent Gastrin/CCK-B receptor antagonist AG-041R was developed. Core oxindole stereochemistry was established by asymmetric alkylation of oxindole enolates with bromoacetic acid esters, using l-menthol as a chiral auxiliary. The key alkylation reaction of the oxindole enolates generated tetrasubstituted chiral intermediates with high diastereoselectivity. The stereoselective alkylation reactions are described in detail.",10.1021/jo061541v,2006-09-30,0.6756295124673627
Journal of Organic Chemistry,Enantioselective Synthesis of (−)-<i>cis</i>-Clavicipitic Acid,An enantioselective synthetic method for (-)-cis-clavicipitic acid (1) was reported. 1 was obtained in 10 steps (99% ee and 20% overall yield) from 1H-indole-3-carboxylic acid methyl ester (9) via asymmetric phase-transfer catalytic alkylation and diastereoselective Pd(II)-catalyzed intramolecular aminocyclization as key steps.,10.1021/jo071162h,2007-09-18,0.6756159807118962
Organic Process Research & Development,Development of a Scalable Process for an IL-17A Inhibitor LY3509754: Part I: Synthesis of the Pyridazinyl Imidazolidinone Intermediate Enabled by Biocatalysis and CSTR Technologies,"Process development and scale-up of the synthesis of a pyridazinyl imidazolidinone intermediate for the production of an imidazo[1,2- b ]pyridazine IL-17A inhibitor are described. A transamination process was developed for the preparation of ( S )-3,3,3-trifluoropropane-1,2-diamine, eliminating an unstable enamine intermediate that significantly limited the scalability of the original asymmetric hydrogenation route. A CSTR continuous flow process was developed for the carbonylation of N -(6-chloropyridazin-3-yl)pivalamide under cryogenic conditions that successfully suppressed product decomposition, improving the isolated yield to ∼60% from the ∼40% yield of the batch mode process. A robust KRED process was developed for the reduction of N -(6-chloro-5-(2-methoxyacetyl)pyridazin-3-yl)pivalamide to the corresponding chiral alcohol, which was further derivatized as its triflate for the S N 2 reaction with ( S )-3,3,3-trifluoropropane-1,2-diamine and treated with carbonyl diimidazole to assemble the target pyridazinyl imidazolidinone intermediate. The developed process was successfully scaled up to deliver 157 kg of the pyridazinyl imidazolidinone intermediate to support the production of the final drug substance, demonstrating the robustness of the optimized process.",10.1021/acs.oprd.5c00003,2025-04-03,0.6755780290696703
Tetrahedron,"A gentle and efficient route for the deoxygenation of sulfoxides using catecholborane (HBcat; cat=1,2-O2C6H4)",,10.1016/j.tetlet.2004.09.068,2004-10-05,0.6755566347076566
Organic Process Research & Development,"An Efficient Large-Scale Synthesis of Methyl 5-[2-(2,5-Dimethoxyphenyl)ethyl]-2-hydroxybenzoate","Methyl 5-[2-(2,5-dimethoxyphenyl)ethyl]-2-hydroxybenzoate ( 1 ) is a new chemical entity designed by Novartis Pharmaceuticals Corporation for the treatment of hyperproliferative and inflammatory disorders and cancer. Development of a prototype adequate process for its preparation is described. The finalized process was six steps in length and started with the commercially available compounds 2,5-dimethoxybenzaldehhyde and 5-formylsalicylic acid. The methyl ester of 5-formylsalicylic acid was condensed with dimethyl [(2,5-dimethoxyphenyl)methyl]phosphonate, prepared from 2,5-dimethoxybenzaldehyde in three steps, to afford methyl 5-[2-(2,5-dimethoxyphenyl)ethenyl]-2-hydroxy-( E )-benzoate. Without purification, this intermediate was hydrogenated using 10% Pd/C at 40 °C to afford 1, in >99.5% purity after recrystallization from absolute ethanol. The process research into the Horner−Wadsworth−Emmons-type olefination and a bromination reaction are also discussed; improvements in these transformations permitted elimination of column chromatography.",10.1021/op9701043,1997-07-01,0.6755463079586733
Organic Process Research & Development,Development and Scale-Up of an Asymmetric Synthesis Process for Alogliptin,"High Resolution Image Download MS PowerPoint Slide Alogliptin ( 1 ) benzoate is a potent, highly selective inhibitor of serine protease dipeptidyl-peptidase IV, approved by US FDA for the treatment of type 2 diabetes. Herein, we report a more cost-effective process that includes ruthenium-catalyzed asymmetric hydrogenation followed by Hofmann rearrangement of 2-((6-chloro-3-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2 H )-yl)methyl)benzonitrile ( 10 ) to introduce a chiral amino moiety at a late stage. Use of an inexpensive and readily available nicotinamide ( 6 ) for a chiral aminopiperidine core and iodobenzene diacetate (PIDA) under mild and specific conditions allowed us to access 1 with excellent total yield and comparable quality to that manufactured by the original process.",10.1021/acs.oprd.0c00544,2021-02-10,0.6755403383825083
Journal of Organic Chemistry,Enantioselective Synthesis of a Furan Lignan (+)-Sylvone,"A synthesis of natural tetrahydrofuran lignan (+)-sylvone is achieved starting from methyl allenoate in 5 steps. The synthesis begins from an enantioselective aldol reaction of methyl allenoate with 3,4-dimethoxybenzaldehyde to afford α-addition aldol adduct. Key steps for the synthesis of sylvone include an oxacyclization of the α-hydroxy allenyl adduct followed by a Michael addition of a 1,3-dithiane derivative to establish a sylvone skeleton with suitable stereoselections.",10.1021/acs.joc.5b01677,2015-09-28,0.6755396432757644
Organic Letters,"Synthesis of Alfaprostol and PGF<sub>2α</sub> through 1,4-Addition of an Alkyne to an Enal Intermediate as the Key Step","The veterinary drug Alfaprostol and prostaglandin PGF 2α have been synthesized in just nine steps. The strategy involved the conjugate addition of an alkyne to a bicyclic enal, available in three steps by a proline-catalyzed aldol reaction of succinaldehyde. In the case of Alfaprostol, this resulted in the shortest synthesis reported to date. For PGF 2α, this approach improved our previous route by making the 1,4-addition and ozonolysis more operationally simple.",10.1021/acs.orglett.7b03057,2017-10-24,0.6755242853251457
European Journal of Organic Chemistry,An Expeditious Synthesis of the Dendrobatid Indolizidine Alkaloid 167B,"The synthesis of the racemic title alkaloid 1 has been accomplished in eight steps and 7.2% overall yield from pyrrolidine-2-thione (5) and ethyl hex-2-enoate (6). Key steps include a ring closure that takes advantage of the nucleophilicity of a vinylogous urethane 8, and stereoselective reduction of the C=C double bond of a bicyclic vinylogous amide 12.",10.1002/(sici)1099-0690(199805)1998:5<865::aid-ejoc865>3.3.co;2-v,1998-05-01,0.6755148805790888
European Journal of Organic Chemistry,An Expeditious Synthesis of the Dendrobatid Indolizidine Alkaloid 167B,"The synthesis of the racemic title alkaloid 1 has been accomplished in eight steps and 7.2% overall yield from pyrrolidine-2-thione (5) and ethyl hex-2-enoate (6). Key steps include a ring closure that takes advantage of the nucleophilicity of a vinylogous urethane 8, and stereoselective reduction of the C=C double bond of a bicyclic vinylogous amide 12.",10.1002/(sici)1099-0690(199805)1998:5<865::aid-ejoc865>3.0.co;2-3,1998-05-01,0.6755148805790888
Tetrahedron,Total synthesis of (±) zoapatanol: a stereospecific synthesis of a key intermediate,,10.1016/s0040-4039(01)81818-9,1981-01-01,0.6755040122493351
Synthesis,Hydroxycyclopentanone Derivativesfrom<scp>d</scp>-Mannose via Ring Closing Metathesis:An Improved Synthesis of a Key Intermediate of Tricyclo-DNA,"A large scale, 10 step synthesis of cyclopentanone 1, starting from the chiral pool compound d-mannose, is described. The synthesis proceeds via a ring closing metathesis reaction as the key step in an overall yield of 23%. Cyclopentanone 1 is a central intermediate for the synthesis of tricyclo-DNA.",10.1055/s-2003-39177,2003-01-01,0.6755015177055765
Journal of Organic Chemistry,"Practical Synthesis of ( <i>R</i> )-4-Mercaptopyrrolidine-2-thione from <scp>l</scp> -Aspartic Acid. Preparation of a Novel Orally Active 1-β-Methylcarbapenem, TA-949","A facile and economical synthesis of a novel orally active 1-beta-methylcarbapenem, TA-949 (1), is described. The key process involves an efficient synthesis of the C-2 side chain (R)-4-mercaptopyrrolidine-2-thione 2 from L-aspartic acid and the construction of the 1-beta-methylcarbapenem skeleton. The mercapto group of 2 with an R-configuration was formed via deaminative bromination of the amino group of L-aspartic acid beta-methyl ester hydrochloride 12 followed by a complete S(N)2-type substitution with potassium benzenemethanethiolate. High-yield amination and cyclization of the chloride 15 to the pyrrolidin-2-one 16 was accomplished by a simple treatment with ammonia. Thiation of 16 and the Birch reduction of the resultant thiolactam 18 provided the C-2 side chain 2 in high yield with the asymmetric center retained as such. The side chain 2 was installed into the 1-beta-methylcarbapenem skeleton either by coupling with the vinyl phosphate 5 or by the use of the counterattack strategy involving the Dieckmann-type cyclization of the thioester 8. Removal of the protective groups of the coupling product 6 followed by esterification provided TA-949 (1) in high yield.",10.1021/jo991461+,2000-01-01,0.6754844488012935
Synlett,Improved Synthesis of Benz[<i>a</i>]acephenanthrene,"A convenient, three-step synthesis of benz[a]acephenanthrene (6) from commercially available materials is described.",10.1055/s-2002-34878,2002-01-01,0.6754591756400955
Journal of the American Chemical Society,Total Synthesis of (−)-Corilagin,"The synthesis of corilagin was achieved by the integration of the development of the oxidative coupling of the symmetrically protected gallates and the temporarily ring-opened synthetic route for the 3,6-hexahydroxydiphenoyl (HHDP) bridge. This is the first total synthesis of the 1C4/B-ellagitannins, which contain ring-flipped glucose.",10.1021/ja803111z,2008-05-28,0.6754310061649715
Tetrahedron,"Synthesis of dihydroxylated prolines and iminocyclitols from five-membered endocyclic enecarbamates. Total synthesis of the potent glycosidase inhibitor (2R,3R,4R,5R)-2,5-dihydroxymethyl-3,4-dihydroxypyrrolidine (DMDP)",,10.1016/s0040-4039(03)00017-0,2003-02-01,0.6754222009996474
Tetrahedron,Scalable synthesis of the L/N ring of maitotoxin,,10.1016/j.tetlet.2024.155221,2024-07-29,0.6754020731378825
Journal of Organic Chemistry,A Second-Generation Total Synthesis of (+)-Phorboxazole A,"A highly convergent second-generation synthesis of (+)-phorboxazole A has been achieved. Highlights of the synthetic approach include improved Petasis-Ferrier union/rearrangement conditions on a scale to assemble multigram quantities of the C(11-15) and C(22-26) cis-tetrahydropyrans inscribed with the phorboxazole architecture, a convenient method to prepare E- and Z-vinyl bromides from TMS-protected alkynes utilizing radical isomerization of Z-vinylsilanes, and a convergent late-stage Stille union to couple a fully elaborated C(1-28) macrocyclic iodide with a C(29-46) oxazole stannane side chain to establish the complete phorboxazole skeleton. The synthesis, achieved with a longest linear sequence of 24 steps, proceeded in 4.6% overall yield.",10.1021/jo7018152,2008-01-24,0.6753889221990584
Synthesis,A New Route to a Chiral Synthon for the Total Synthesis of Estrone,"All articles of this category (2 S ,3 S )-2-(2-Bromoethyl)-3-ethenyl-2-methylcyclopentanone 2,2-dimethyl-1, 3-propanediyl acetal (Synthon C) is a chiral synthon for the total synthesis of estrone. Synthon C is prepared from 3a-hydroxy-7a-methyloctahydroindeno-1, 5-dione by a multistep sequence, the key steps of which consist of the regioselective Baeyer-Villiger oxidation of the starting dione and the stereospecific catalytic hydrogenation of an intermediate unsaturated bicyclic lactone.",10.1055/s-1987-28051,1987-01-01,0.6753757525233074
Journal of Organic Chemistry,"Scaling Amatoxin Synthesis with an Improved Route to (2<i>S</i>,3<i>R</i>,4<i>R</i>)-Dihydroxyisoleucine Exemplified by a Toxic, Clickable α-Amanitin Analogue","Here we report a scalable synthesis of the key amino acid residue, (2 S,3 R,4 R )-4,5-dihydroxyisoleucine (DHIle) in α-amanitin, that in turn enables the scalable synthesis of an equipotent analogue, Asn ( N -ethylazide) -S,6′-dideoxy-α-amanitin, suitable for CuAAC conjugation to empower studies on therapeutic antibody-drug conjugates.",10.1021/acs.joc.0c03022,2021-03-12,0.6752872951578471
Journal of Organic Chemistry,Enzymatic- and Iridium-Catalyzed Asymmetric Synthesis of a Benzothiazepinylphosphonate Bile Acid Transporter Inhibitor,"A synthesis of the benzothiazepine phosphonic acid 3, employing both enzymatic and transition metal catalysis, is described. The quaternary chiral center of 3 was obtained by resolution of ethyl (2-ethyl)norleucinate (4) with porcine liver esterase (PLE) immobilized on Sepabeads. The resulting (R)-amino acid (5) was converted in two steps to aminosulfate 7, which was used for construction of the benzothiazepine ring. Benzophenone 15, prepared in four steps from trimethylhydroquinone 11, enabled sequential incorporation of phosphorus (Arbuzov chemistry) and sulfur (Pd(0)-catalyzed thiol coupling) leading to mercaptan intermediate 18. S-Alkylation of 18 with aminosulfate 7 followed by cyclodehydration afforded dihydrobenzothiazepine 20. Iridium-catalyzed asymmetric hydrogenation of 20 with the complex of [Ir(COD)2BArF] (26) and Taniaphos ligand P afforded the (3R,5R)-tetrahydrobenzothiazepine 30 following flash chromatography. Oxidation of 30 to sulfone 31 and phosphonate hydrolysis completed the synthesis of 3 in 12 steps and 13% overall yield.",10.1021/jo402311e,2013-11-20,0.6752802487600215
Journal of Organic Chemistry,"Total Synthesis of <i>e</i><i>nt</i>-Cholesterol via a Steroid C,D-Ring Side-Chain Synthon","For the first time, one of the two enantiomers of cholesterol (ent-cholesterol) has been synthesized by a synthetic route that starts from a precursor containing the D-ring and entire side chain of cholesterol. As part of the reported synthetic route, a method of general utility for the large scale (>10 g) preparation of each enantiomer of [1 alpha(R*),7a alpha]-1-(1,5-dimethylhexyl)-1,2,3,6,7,7a-hexahydro-7a-methyl-5H-inden-5-one, C,D ring-side chain synthons that can be used for the synthesis of enantiomers of vitamin D(3), cholesterol, and their analogues was also developed. Using the enantiomer of the C,D-ring side-chain synthon that leads to ent-cholesterol, the A- and B-rings were elaborated from a linear fragment that is sequentially cyclized to form the steroid B- and A-rings. Using this route, ent-cholesterol was prepared in 23 steps from the methyl ester of (1 alpha,5 alpha,6 alpha)-(+/-)-6-methyl-2-oxo-bicyclo[3.1.0]hexane-1-carboxylic acid in a total yield of 2.6%.",10.1021/jo025535k,2002-06-04,0.6752771116686187
Journal of the American Chemical Society,Total Synthesis and Biological Mode of Action of Largazole: A Potent Class I Histone Deacetylase Inhibitor,"The efficient total synthesis of the recently described natural substance largazole (1) and its active metabolite largazole thiol (2) is described. The synthesis required eight linear steps and proceeded in 37% overall yield. It is demonstrated that largazole is a pro-drug that is activated by removal of the octanoyl residue from the 3-hydroxy-7-mercaptohept-4-enoic acid moiety to generate the active metabolite 2, which is an extraordinarily potent Class I histone deacetylase inhibitor. Synthetic largazole and 2 have been evaluated side-by-side with FK228 and SAHA for inhibition of HDACs 1, 2, 3, and 6. Largazole and largazole thiol were further assayed for cytotoxic activity against a panel of chemoresistant melanoma cell lines, and it was found that largazole is substantially more cytotoxic than largazole thiol; this difference is attributed to differences in the cell permeability of the two substances.",10.1021/ja8033763,2008-07-19,0.675261564072354
Journal of Organic Chemistry,A Divergent Route to Eravacycline,"A convergent route to eravacycline (1) has been developed by employing Michael-Dieckmann cyclization between enone 3 and a fully built and protected left-hand piece (LHP, 2). After construction of the core eravacycline structure, a deprotection reaction was developed, allowing for the isoxazole ring opening and global deprotection to be achieved in one pot. The LHP is synthesized from readily available 4-fluoro-3-methylphenol in six steps featuring a palladium-catalyzed phenyl carboxylation in the last step.",10.1021/acs.joc.6b02442,2016-12-22,0.6752027431098137
Synthesis,An Efficient Synthesis of (±)-3-Amino-2-(4-chlorophenyl)-propylphosphonic Acid (PHACLOFEN),"All articles of this category A three step, highly efficient synthesis of the GABA-B antagonist, Phaclofen, is described, which features a Michael addition of a phosphonate to a ß-nitrostyrene.",10.1055/s-1989-27279,1989-01-01,0.6751894832427969
Journal of Organic Chemistry,"A General Approach toward the Synthesis of <i>C</i>-Nucleoside Pyrazolo[1,5-<i>a</i>]-1,3,5-triazines and Their 3‘,5‘-Bisphosphate C-Nucleotide Analogues as the First Reported in Vivo Stable P2Y<sub>1</sub>-Receptor Antagonists","In our effort to identify potent purinergic P2Y(1) receptor antagonists as potent platelet aggregation inhibitors with enhanced metabolic stability, we developed an efficient route for the large-scale preparation of 2'-deoxy-C-nucleosides of pyrazolo[1,5-a]-1,3,5-triazine. The key strategic elements of this novel synthetic approach involved the following: (i) the use of a novel activating group, the N-methyl-N-phenylamino group, which was easily generated in high yield by treatment of the pyrazolo[1,5-a]-1,3,5-triazin-4-one (5) with phosphorus oxychloride and dimethylaniline under high pressure, (ii) a regio- and stereospecific palladium-mediated coupling reaction of the readily available unprotected glycal 1,4-anhydro-2-deoxy-D-erythro-pent-1-enitol (4b) and the 8-iodo derivative (16), and (iii) the stereoselective reduction of the ketone group of the furanosyl ring followed by the subsequent displacement of the N-methyl-N-phenylamino group upon treatment with methylamine. The beta configuration at the anomeric C-1' position of the glycal moieties was perfectly retained throughout this conversion. This procedure afforded 8-(2'-deoxy-beta-D-ribofuranosyl)-2-methyl-4-(N-methylamino)pyrazolo[1,5-a]-1,3,5-triazine (21) and 8-(2'-deoxy-beta-D-xylofuranosyl)-2-methyl-4-(N-methylamino)pyrazolo[1,5-a]-1,3,5-triazine (24) with an overall yield of 50% and 39%, respectively. Finally, the conversion of nucleosides 21 and 24 to the pyrazolotriazine C-nucleotides 3',5'-bisphosphate 2 and 3',5'-cyclophosphate 26 is also described herein and represents the first reported nucleotide derivatives within the pyrazolo[1,5-a]-1,3,5-triazine series. Preliminary biological testing has shown that compound 2 strongly inhibits ADP-induced human platelet aggregation and shape change and possesses significant efficacies 30 min after injection in rat, highlighting a strong P2Y(1)-receptor antagonist activity in vitro combined with a prolonged duration of action in vivo.",10.1021/jo026268l,2002-10-16,0.6751329854356182
Journal of Organic Chemistry,First Total Synthesis of <i>e</i><i>nt</i>-Gelsedine via a Novel Iodide-Promoted Allene <i>N</i>-Acyliminium Ion Cyclization,"The first total synthesis of the oxindole alkaloid gelsedine (1) starting from (S)-malic acid is described. The key step is a novel iodide-promoted intramolecular reaction of an allene with an N-acyliminium ion intermediate which provided in a single step the bicyclic vinyl iodide 11. Other important steps are the highly stereoselective Pd-catalyzed Heck cyclization of N-methylanilide 23a which led to the desired spiro-oxindole 24a, the fully regioselective intramolecular oxymercuration of 25a to the desired cyclic ether, and the remarkable oxindole N-demethylation of 29 via a radical mechanism by using dibenzoyl peroxide. The total synthesis was concluded by the stereoselective introduction of the ethyl group from the bis-Boc compound 41 followed by methoxylation of the oxindole nitrogen. This total synthesis leads to the unnatural (+)-enantiomer of gelsedine in 21 steps and 0.10% overall yield.",10.1021/jo001119t,2000-10-27,0.6750521625125342
Journal of Organic Chemistry,Total Synthesis of Tricolorin A,"Tricolorin A (1) is a novel tetrasaccharide macrolactone that is a natural herbicide. In this paper is reported a total synthesis of 1. Coupling of hydroxy ester 18 with D-fucosyl trichloroacetimidate 23 gave fucoside 24. Removal of the C-2 pivaloyl group of 24 followed by coupling with D-glucosyl trichloroacetimidate 29 resulted in isolation of disaccharide 30. Saponification of the ester groups of 30 and subsequent selective macrolactonization of the acid diol 31 by the Yonemitsu protocol gave only the desired lactone 32. The key step in the assembly of disaccharide glycosyl trichloroacetimidate 52 was coupling L-rhamnoside 47 with L-rhamnosyl trichloroacetimidate 43. Attempts to couple lactone disaccharide 32 with disaccharide 52 were unsuccessful. Using an alternate plan for assembly of the tetrasaccharide, reaction of disaccharide glycosyl trichloroacetimidate 58 with disaccharide 37 gave tetrasaccharide 59. Diester lactone 63 was generated by selective macrolactonization of tetrasaccharide acid triol 60, again using the Yonemitsu protocol, followed by addition of the chiral side chain acid to the reaction vessel. Synthetic tricolorin A (1) was obtained by deprotection of 63. Starting from fucose, glucose, rhamnose, and (S)-1-octyn-3-ol, the synthesis required 39 steps overall. The longest linear sequence was 14 steps, with an overall yield for this longest linear sequence of 6%.",10.1021/jo971413u,1997-11-01,0.6750484416577885
Organic Letters,Total Synthesis of a Marine Alkaloid from the Tunicate <i>Dendrodoa grossularia</i>,"A short synthesis of an indole marine alkaloid (1) from the tunicate Dendrodoa grossularia is described. The key step in the synthesis involves a novel twist on an underutilized oxazole rearrangement, which produces the quaternary stereocenter in the molecule.",10.1021/ol801375k,2008-08-05,0.6750192700276532
Journal of Organic Chemistry,Total Syntheses of (−)-Fructigenine A and (−)-5-<i>N</i>-Acetylardeemin,"The first total synthesis of (-)-fructigenine A and a novel approach to (-)-5-N-acetylardeemin through a common imine intermediate (+)-3 are described. The key steps include highly enantioselective preparation of (+)-3 via domino olefination/isomerization/Claisen rearrangement (OIC) of 5, reductive cyclization (RC), and regioselective oxidation of (-)-4 and a novel assembly of the pyrazino ring of these alkaloids via Ugi three-component reaction/cyclization of (+)-3 with the corresponding amino acid and isonitrile.",10.1021/jo9023107,2010-01-14,0.6749488427560589
Organic Letters,A Practical and Efficient Synthesis of the C-16−C-28 Spiroketal Fragment (CD) of the Spongistatins,"A practical and efficient route to the CD spiroketal (C-16-C-28) of the spongistatins is reported. Two stereocenters are introduced from chiral building blocks with the remainder introduced by substrate-controlled transformations. The key beta-keto-1,3-dithiane intermediate is generated by a dithiol conjugate addition to an ynone and the 1,3-dithiane unit in the C-ring plays a key role in the spiroketalization and subsequent epimerization. The synthesis requires 24 steps, with a longest linear sequence of 19 steps in an overall yield of 14.5% (for the longest linear sequence). [reaction: see text]",10.1021/ol035848h,2003-11-11,0.6749111036734075
Synlett,Scalable Synthesis of l-allo-Enduracididine: The Unusual Amino Acid Present in Teixobactin,Abstract A scalable synthesis of l-allo-enduracididine is achieved from commercially available (S)-glycidol in ten linear steps involving well-established synthetic transformations. The synthetic route is flexible and can be used to synthesize all four diastereomers by changing the stereochemistry of glycidol and Sharpless asymmetric dihydroxylation reagent.,10.1055/a-1528-0625,2021-06-13,0.6748884531939728
Tetrahedron,The synthesis of dithyreanitrile,"An efficient synthesis of dithyreantrile (1), a novel insect antifeedant, is presented.",10.1016/s0040-4039(00)77496-x,1993-02-01,0.6748585339668824
Organic Process Research & Development,Scalable Synthesis of a Cis-Substituted Cyclobutyl-Benzothiazole Pyridazinone: Process Development of an Efficient Copper Catalyzed C–N Cross-Coupling Reaction,"A scalable process for the preparation of 2-(2-( cis -3-(piperidin-1-yl)cyclobutyl)benzothiazol-6-yl)pyridazin-3(2H)-one in multi-kilogram amounts and in high purity has been developed. The key features of this synthesis are the copper-catalyzed C–N cross-coupling reaction and the development of a highly diastereoselective reductive amination using NaBH(OPiv) 3 as a reducing agent. Controls were implemented to minimize both base- and acid-catalyzed isomerization of the 1,3- cis -substituted cyclobutane ring.",10.1021/op3002883,2013-01-02,0.6748301931428686
Synlett,"An Improved Synthesis of CENTA, a Chromogenic Substrate for β-Lactamases","7-β-Thien-2-yl-acetamido-3-[(4-nitro-3-carboxyphenyl)thiomethyl]-3-cephem-4-carboxylic acid (CENTA) is a yellow chromogenic β-lactamases (BL) substrate. It hydrolyses readily in the presence of all BL and is therefore suitable for kinetic studies, the detection of BL enzymes in crude extracts and chromatographic fractions. CENTA is commercially available at a high price because of the cumbersome synthetic protocol, the only currently available for its preparation. Here we describe a new efficient and improved process for the preparation of CENTA. Starting from the easily available 7-aminocephalosporanic acid (7-ACA) through a three-step synthesis, CENTA was obtained with a 75% overall yield. The newly developed process proceeds through a pivotal intermediate in cephalosporin chemistry, which may be used as starting compound for the development of new cephalosporin derivatives.",10.1055/s-0035-1562454,2016-07-07,0.6748144085577924
Synthesis,Total Synthesis of the Pyrrole Alkaloids Strychnuxinal and Strychnuxin,"Abstract The first asymmetric total syntheses of the fused-pyrrole alkaloids strychnuxinal and strychnuxin have been achieved in 6 and 7 steps, respectively, starting from commercially available (±)-4-chlorostyrene oxide. Key steps in the synthetic route include a regioselective epoxide opening, a reductive etherification sequence to form the central 1,4-oxazine ring, and a late-stage phenol synthesis using a mild palladium-catalyzed coupling reaction. Notably, the optimized synthetic sequence presented avoids the use of traditional protecting groups. Total synthesis of these two structurally related natural products confirmed both their constitution (via NMR and X-ray crystallography) and their absolute configuration (via optical rotation).",10.1055/s-0043-1763603,2023-11-07,0.6748113714728203
Organic Process Research & Development,Application of C–H Functionalization in the Development of a Concise and Convergent Route to the Phosphatidylinositol-3-kinase Delta Inhibitor Nemiralisib,"This paper describes the development of an improved and scalable method for the manufacture of nemiralisib, a phosphatidylinositol-3-kinase delta inhibitor. Incorporation of three consecutive catalytic reactions, including a palladium-catalyzed C–H functionalization and an iridium-catalyzed borylation, significantly simplified and shortened the synthetic sequence. The revised route was successfully implemented in a pilot plant on a multikilogram scale to deliver >100 kg of product.",10.1021/acs.oprd.0c00486,2021-02-09,0.6747828465876001
Tetrahedron,Efficient one-step synthesis of 3-amino-6-arylpyridazines,,10.1016/s0040-4039(01)00134-4,2001-03-01,0.6747513991875308
Journal of Organic Chemistry,A Total Synthesis of (±)-Leuconodines D and E,"A new synthetic route for a short synthesis of (±)-leuconodines D and E was developed. The rapid construction of the diaza[5.5.6.6]fenestrane core was achieved through a sequence involving a Pd-catalyzed aerobic oxidative Heck cross-coupling reaction for the construction of indole δ-lactam containing a full-carbon quaternary center, an epoxidative cyclization for the assembly of pyrroloindole, and a ring-closing metathesis for the construction of the piperidine ring. As a result, the total synthesis of (±)-leuconodine E ( 2 ) was achieved for the first time within a 10-step linear sequence, and a more concise total synthesis of (±)-leuconodine D ( 1 ) was accomplished within a 12-step linear sequence from the commercially available tryptophol.",10.1021/acs.joc.9b02054,2019-09-19,0.6747433905197319
Journal of Organic Chemistry,An Enantioselective Total Synthesis of (+)-Duocarmycin SA,"An efficient, concise enantioselective total synthesis of the potent antitumor antibiotic (+)-duocarmycin SA is described. The invented route is based on a disconnection strategy that was devised to facilitate rapid and efficient synthesis of key core compounds to enable preclinical structure-activity relationship investigations. The key tricycle core was constructed with a highly enantioselective indole hydrogenation to set the stereocenter and a subsequent hitherto unexplored vicarious, nucleophilic-substitution/cyclization sequence to effectively forge a final indole ring. Additionally, the development of a stable sulfonamide protecting group capable of mild chemoselective cleavage greatly enhanced sequence yield and throughput. An understanding of key reaction parameters ensured a robust, reproducible sequence easily executable on decagram scales to this highly promising class of compounds.",10.1021/acs.joc.8b00285,2018-03-20,0.6747409235266406
Tetrahedron,"New synthesis of 2-aminobicyclo[2.1.1]hexane-2,5-dicarboxylic acid-I (ABHxD-I), a potent metabotropic receptor agonist",,10.1016/s0040-4039(00)00588-8,2000-05-01,0.6747335553082003
Organic Process Research & Development,"Development of a New Synthetic Route of a Non-Peptide CCR5 Antagonist, TAK-779, for Large-Scale Preparation","A new large-scalable preparation of TAK-779 ( 1 ), a non-peptide CCR5 antagonist, has been developed. The route selection was focused on in the process research. The selective reduction of commercially available benzonitrile derivative ( 4 ) as the starting material with sodium bis(2-methoxyethoxy)aluminum hydride followed by the Wittig reaction, hydrogenation, and intramolecular acylation gave benzocycloheptanone ( 7 ) in good yield. The conversion of α,β-unsaturated carboxylic acid ( 8 ) led from 7 to benzyl alcohol ( 9 ) and shortened the number of steps using non-protected 4-aminobenzyl alcohol. The reductive alkylation of Me 2 NH and tetrahydro-4 H -pyran-4-one ( 12 ) smoothly gave a tertiary amine ( 3 ). The coupling of 2 chlorinated 9, and 3 successfully led to an ammonium chloride ( 1 ). A new inexpensive preparation which did not require a chromatographic method was achieved.",10.1021/op000074v,2000-10-12,0.6747057349372622
Organic Letters,A Direct and Efficient Total Synthesis of the Tubulin-Binding Agents Ceratamine A and B; Use of IBX for a Remarkable Heterocycle Dehydrogenation,"The total synthesis of the tubulin-binding agents ceratamine A and B is reported, along with des-methyl analogs, via a synthetic route that is high-yielding and operationally efficient. The synthetic route involved a Beckmann rearrangement to form an azepine ring precursor, a Knoevenagel condensation to install the benzylic side chain, and an effective imidazole annulation onto an alpha-aminoketone precursor with a protected S-methylisothiourea. Final dehydrogenation proved remarkably facile using IBX.",10.1021/ol900709n,2009-04-22,0.674703906146022
Organic Process Research & Development,"Development of a Scalable Synthesis toward a KRAS G12C Inhibitor Building Block Bearing an All-Carbon Quaternary Stereocenter, Part 2: Asymmetric Synthesis via Shi Epoxidation","The development of a scalable asymmetric synthesis of KRAS G12C inhibitor building block 1 is described. The all-carbon quaternary stereocenter was installed enantioselectively via Shi epoxidation, followed by a newly discovered regioselective LaCl 3 ·2LiCl-catalyzed epoxide opening. Subsequent organocatalyzed oxidation provided the requisite ketone, which underwent the final assembly of the heterocyclic core, delivering 1 with high chemical and enantiomeric purities in 40% overall yield in only five steps, enabling robust and rapid manufacturing of over 300 kg of 1 .",10.1021/acs.oprd.3c00363,2024-01-05,0.6746981804484258
Journal of Organic Chemistry,Enantioselective Synthesis of Thailanstatin A Methyl Ester and Evaluation of <i>in Vitro</i> Splicing Inhibition,"Thailanstatin A has been isolated recently from the fermentation broth of B. thailandensis MSMB43. We describe here an enantioselective convergent synthesis of thailanstatin A methyl ester and evaluation of its splicing activity. Synthesis of both highly functionalized tetrahydropyran rings were carried out from commercially available tri- O-acetyl-d-glucal as the key starting material. Our convergent synthesis involved the synthesis of both tetrahydropyran fragments in a highly stereoselective manner. The fragments were then coupled using cross-metathesis as the key step. The synthesis of the diene subunit included a highly stereoselective Claisen rearrangement, a Cu(I)-mediated conjugate addition of MeLi to set the C-14 methyl stereochemistry, a reductive amination reaction to install the C16-amine functionality, and a Wittig olefination reaction to incorporate the diene unit. The epoxy alcohol subunit was synthesized by a highly selective anomeric allylation, a Peterson olefination, and a vanadium catalyzed epoxidation that installed the epoxide stereoselectively. Cross-metathesis of the olefins provided the methyl ester derivative of thailanstatin A. We have carried out in vitro splicing studies of the methyl ester derivative, which proved to be a potent inhibitor of the spliceosome.",10.1021/acs.joc.8b00593,2018-04-26,0.6746978648743996
Synthesis,Synthesis of the Imidazole-Derived AT1-Selective ANG II Receptor Antagonist HR 720 Utilizing Reductive Amination as Key Step,"All articles of this category The straightforward synthesis of the (1-methylbiphenylsulfonyl)-urea substituted imidazole HR 720, an orally active ANG II receptor antagonist, by reductive amination of 2’-sulfonamidobiphenylcarbaldehydes, derived from Suzuki-type phenyl-phenyl coupling procedures, as key step is described. Suzuki coupling - reductive amination - cyclodehydration - imidazoles - biphenylsulfonylureas and -carbamates",10.1055/s-1996-4383,1996-11-01,0.6746414412466787
Organic Process Research & Development,Practical and Scalable Synthetic Method for Preparation of Dolutegravir Sodium: Improvement of a Synthetic Route for Large-Scale Synthesis,"A practical and scalable synthetic method to obtain dolutegravir sodium ( 1 ) was established starting from the readily accessible material maltol ( 2 ). This synthetic method includes a scalable oxidation process of maltol and palladium-catalyzed amidation for introduction of an amide moiety, leading to a practical manufacturing method in short synthetic steps. The synthetic method demonstrated herein enables multikilogram scale manufacturing of 1 of high purity.",10.1021/acs.oprd.8b00409,2019-03-01,0.6746115418956807
Organic Process Research & Development,First-Generation Process Development for the Synthesis of Baloxavir Marboxil: Early-Stage Development of Synthetic Methods to Prepare Baloxavir Marboxil Intermediates,"Described herein is the discovery and development of a process to prepare chiral triazinanone R -3 and diastereomeric intermediate 5, the key intermediates in the synthesis of the cap-dependent endonuclease inhibitor baloxavir marboxil ( 1 ), which can suppress the replication of influenza virus. Chiral triazinanone R -3 was obtained via optical resolution of its racemic form rac -3 . Diastereomeric intermediate 5 was obtained by the condensation reaction of triazinanone R -3 and thiepin alcohol 4 using a combination of T3P and MsOH. These reactions were performed successfully on kilogram scale and were critical to the establishment of the baloxavir marboxil manufacturing process.",10.1021/acs.oprd.3c00514,2024-04-03,0.6745982842354769
Tetrahedron,A stereoselective route to the key intermediate of 1β-methylcarbapenems by chemicoenzymatic approach,,10.1016/s0040-4039(01)80338-5,1989-01-01,0.6745974628226625
Angewandte Chemie International Edition,β‐Ketoesters as Mono‐ or Bisnucleophiles: A Concise Enantioselective Total Synthesis of (−)‐Englerin A and B,"A short enantioselective total synthesis of englerin A, a guaiane sesquiterpene with significant in vitro antitumor activity, is reported. Key features of this total synthesis are an organocatalytic asymmetric decarboxylative aldol reaction, a neighboring-group-participating [4+3] cycloaddition, a novel one-pot Heck coupling/regioselective 1,4-hydrosilylation/Tamao-Fleming oxidation cascade, and a kinetic CBS reduction, generating the optically pure natural product in 6.7 % overall yield over twelve steps starting from methylglyoxal. Selective saponification of the more reactive glycolic ester moiety of englerin A also gave (-)-englerin B.",10.1002/anie.201900401,2019-04-02,0.6745897337956545
European Journal of Organic Chemistry,Synthesis and Glycosidase Inhibitory Study of New Polyhydroxylated Indolizidines,"Abstract The synthesis of two polyhydroxylated indolizidines as potenticial glycosidase inhibitors is reported. The piperidine ring was formed by an intramolecular Mannich‐type reaction between ethyl trans ‐4‐oxo‐2‐butenoate and the two β‐amino ketones (–)‐1‐(2‐methyl‐1,3‐dioxan‐2‐yl)propan‐2‐amine and(+)‐1‐(benzyloxymethyl)‐2‐(2‐methyl‐1,3‐dioxan‐2‐yl)ethylamine. The synthesis of this amine was performed in eight steps from L ‐aspartic acid. The key steps of the formation of the framework involved dihydroxylation, nucleophilic substitution, and reduction. The last hydroxy group was introduced by hydrolysis of the acetal moiety followed by reduction of the resulting ketone. The inhibitory properties of the two synthesized indolizidines were evaluated against a variety of commercial glycosidases. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2008)",10.1002/ejoc.200800684,2008-09-30,0.674537103378024
Tetrahedron,A highly efficient one-step synthesis of (±) dihydroactinidiolide,,10.1016/s0040-4039(00)84278-1,1986-01-01,0.6745368729381245
Journal of Organic Chemistry,Efficient Route to 4a-Methyltetrahydrofluorenes:  A Total Synthesis of (±)-Dichroanal B via Intramolecular Heck Reaction,An efficient new route based on intramolecular Heck cyclization of the diene 11 was developed to prepare the 4a-methyltetrahydrofluorene diterpenoids and utilized for the total synthesis of (+/-)-dichroanal B with significantly improved overall yield.,10.1021/jo052454q,2006-02-28,0.6745358650354331
Synthesis,A Concise Total Synthesis of (±)-Cassumunin C,The first concise and efficient total synthesis of (±)-cassumunin C has been accomplished with a longest linear sequence of seven steps in 11.7% yield. The key steps involve aromatic propargylation and stereoselective reduction of alkynylphenol to the corresponding ( E )-alkenylphenol.,10.1055/s-0034-1378557,2014-08-14,0.6744537359767934
Synthesis,A Practical and Efficient Conversion of Luteolin into Luteoloside,Abstract A new practical and efficient preparation of the flavonoid luteoloside is reported in an excellent overall yield of 40% via a four-step synthetic approach.,10.1055/a-1531-2385,2021-06-17,0.674417824828677
Organic Process Research & Development,"Practical, Facile, and Efficient Approach to Scalable Synthesis of the Flavonoid Derivative GL-V9","GL-V9, an innovative synthetic flavonoid derivative, has been submitted to Investigational New Drug (IND) application to the National Medical Products Administration (NMPA) in 2023 for the treatment of acute myeloid leukemia. This study details the development of an advanced, efficient synthesis pathway for GL-V9, enabling the production of significant quantities of the drug substance to fulfill the needs for forthcoming clinical trials. Characterized by a five-step process under mild conditions─starting with commercially available chrysin and proceeding through Elbs oxidation, O -alkylation, hydrolysis, methylation, and concluding with N -alkylation, this method achieved GL-V9 with exceptional high-performance liquid chromatography purity (>99.5 area %) and an overall yield of 29.1%. Importantly, the synthesis of GL-V9 introduces a versatile framework for the development of other flavonoid scaffolds, underscoring its wide applicability in the field of medicinal chemistry. This scalable and efficient pathway not only facilitates the production of GL-V9 but also opens avenues for exploring novel flavonoid-based therapies.",10.1021/acs.oprd.4c00082,2024-07-31,0.6744132946096977
Synthesis,"A Short, Efficient Synthesis of the Novel Cholinergic Channel Activator, ABT 418, from L-Proline","All articles of this category A short and efficient synthesis of the novel cholinergic channel activator ABT 418, ( S )-3-methyl-5-(1-methyl-2-pyrrolidinyl)isoxazole, has been developed. The four-step route from L-proline afforded the target compound in ca. 35% overall yield in very high chemical and enantiomeric purity. This route has afforded multigram quantities of the clinical candidate and should be amenable to kilogram-scale reactions. ABT 418 was synthesized in four steps (35% yield) from (L)-proline",10.1055/s-1995-4014,1995-07-01,0.6744132116362805
Journal of Organic Chemistry,A Total Synthesis of the Racemic Sesquiterpene Parvifoline,"A total synthesis of the sesquiterpene (±)-parvifoline 1 from the symmetrical naphthalene 4 is reported. The key step of the synthesis was a Stork−Landesman two-carbon ring expansion of β-tetralone 5, which affords 9a with the complete framework of the target. Although many reactions are involved in the sequence, the whole synthesis can be executed in only five synthetic operations and in ≈18% overall yield.",10.1021/jo972092p,1998-04-14,0.6744002062873792
Angewandte Chemie International Edition,Total Synthesis of the Antibiotic Branimycin,"Catch 22: The first total synthesis of branimycin (1) has been achieved by a highly convergent approach in which the vinyl lithium derivative 3 was added to a cis-decalin ketone 2. The route has 22 steps in the longest linear sequence and an overall yield of 2 %. It is highly stereocontrolled, scaleable, and flexible. MOM=methoxymethyl, TBS=tert-butyldimethylsilyl.",10.1002/anie.200906453,2010-02-09,0.6743778464385484
Journal of Organic Chemistry,Total Synthesis of (−)-Cocaine and (−)-Ferruginine,"Total synthesis of tropane alkaloids (-)-cocaine and (-)-ferruginine were accomplished in nine steps each and in 55% and 46% overall yields, respectively, starting from the known Betti base derivative (+)-(7aR,10R,12S)-10-(1H-benzotriazol-1-yl)-7a,8,9,10-tetrahydro-12-phenyl-12H-naphtho[1,2-e]pyrrolo[2,1-b][1,3]oxazine. In this novel route, RCM reaction and 1,3-dipolar cycloaddition were employed as key steps for the enantioselective construction of tropane skeleton and the regioselective introduction of 3-bromo-2-isoxazoline ring as masked cis-2,3-disubstituents. To obtain the desired precursor (2S,5R)-2-allyl-5-vinylpyrrolidine for RCM reaction, we developed a general and practical method for the preparation of enantiopure cis-2,5-disubstituted pyrrolidines bearing alkene- and/or alkyne-containing substituents. We also offered two highly efficient pathways for the conversion of the 3-bromo-2-isoxazoline ring into the desired cis-2,3-disubstituted groups in (-)-cocaine and (-)-ferruginine.",10.1021/jo200069m,2011-03-10,0.6743410436852114
Angewandte Chemie International Edition,Total Synthesis of (+)-Halichlorine: An Inhibitor of VCAM-1 Expression,The diastereoselective addition of the highly functionalized organozinc compound 1 to the aldehyde 2 in the presence of the chiral amino alcohol 3 (-->4) is a key step in the first total synthesis of (+)-halichlorine. A series of protections/deprotections and a macrolaconization complete the synthesis. Halichlorine selectively inhibits the expression of the cell adhesion molecule VCAM-1. TBS=tert-butyldimethylsilyl.,10.1002/(sici)1521-3773(19991203)38:23<3542::aid-anie3542>3.0.co;2-i,1999-11-30,0.674334523413916
Tetrahedron,"An improved synthesis of the C,D-ring pyrromethenone of phytochrome and phytochromobilin",,10.1016/0040-4039(96)01317-2,1996-08-01,0.674314199224975
Organic Process Research & Development,Development of an Alternate Synthesis for a Key JAK2 Inhibitor Intermediate via Sequential C–H Bond Functionalization,The development of an alternative synthetic route to a functionalized imidazopyridazine which strategically streamlines the synthesis and avoids a number of problematic reagents is described. Key to the success of this alternative route is the use of two C–H functionalization reactions: a Pd-catalyzed direct benzylation reaction to functionalize a C–H bond with a substituted benzyl group and a V-catalyzed NMO addition reaction to install a benzylic morpholine moiety.,10.1021/op300344m,2013-01-12,0.6743006647616998
Synlett,An Efficient Synthesis of a Lycobetaine-Tortuosine Analogue: A Potent Topoisomerase Inhibitor,"An efficient gram-scale synthesis that uses a Suzuki cross-coupling reaction to yield 5-methyl-2,9-dimethoxyphenanthridinium chloride, a lycobetaine-tortuosine analogue and potent topoisomerase inhibitor, is presented.",10.1055/s-2006-956482,2006-12-01,0.6742754945759073
Tetrahedron,"Dykellic acid, a novel apoptosis inhibitor from Westerdykella multispora F50733",,10.1016/s0040-4039(99)01367-2,1999-09-01,0.6742387314568724
Synlett,Stereoselective Total Synthesis of (-)-Galantinic Acid,"A concise, practical and stereoselective total synthesis of galantinic acid, constituent of the peptide antibiotic galantin, is reported. The title compound is obtained in six steps via Heathcock-Claisen condensation, Evans reduction and deprotection in 10% overall yield from protected serine. The route described herein thus constitutes the shortest and most efficient procedure for the preparation of the title compound disclosed so far.",10.1055/s-2006-941602,2006-06-01,0.6741825657300355
Synthesis,Formal Total Synthesis of Palmerolide A,"A concise route to macrolactone 38, an advanced intermediate of the Nicolaou/Chen synthesis of palmerolide A, is described. Key steps in our synthesis include a Noyori transfer hydrogenation of an alkynone, chain extension via Claisen rearrangement, and an ADH reaction on an enyne. After reduction of the triple bond, a selective silylation served to differentiate the hydroxy­ groups of the diol, which allowed for the preparation of aldehyde 30 containing already the carbamate function. A HWE reaction produced the substrate for an intramolecular Heck coupling. In contrast to the Stille cyclization, the Heck cyclization produced only the desired 14E,16E-diene. Elaboration of the C-19 side chain led to the key lactone 38.",10.1055/s-0029-1216921,2009-07-30,0.6741604600113761
Tetrahedron,"Synthesis of (±)-mispyric acid, a triterpene inhibitor of DNA polymerase β isolated from Mischocarpus pyriformis",,10.1016/s0040-4039(02)01193-0,2002-08-01,0.6741539211330985
Organic Process Research & Development,"A Concise, Economical, and Diastereoselective Synthesis of Methyl DGJ Isopropylidene:  An Iminocyclitol Molecule Core for Analogue Synthesis","A six-step synthesis of the title compound starting from l -lyxonolactone 2,3-isopropylidene ( 6 ) is described. The synthesis is achieved by conversion of 6 to the C 5 -triflate or C 5 -mesylate 7a or 7b and their displacement by sodium azide to yield the C 5 azido compound 8 . Addition of methylmagnesium bromide and catalytic hydrogenation during which the azide group is reduced to the amine followed by an intramolecular cyclization yields the imine 15 . Concomitant reduction of the imine occurs stereoselectively to yield methyl DGJ isopropylidene ( 5 ) which is isolated via the succinic acid salt and its further neutralization with ammonia. It was found that changing the synthetic sequence, namely, instead of 7a → 8 → 9, the methylmagnesium bromide could be added first to the mesylate 7b, 7b → 11 followed by azide ion displacement 11 → 9 . This modification proved advantageous from the viewpoint of cost, use of methanesulfonyl chloride rather than trifluoromethylsulfonyl chloride, ease of operation, and yield. Methyl DGJ isopropylidene ( 5 ) is an important azasugar precursor because it can undergo N-alkyl substitution via reductive amination and be derivatized at C 2 via the secondary hydroxyl group. The synthesis reported herein allows for the production of mutikilogram amounts of this important key iminocyclitol core.",10.1021/op060100a,2006-08-18,0.6741525915982205
European Journal of Organic Chemistry,Synthesis of Enantiopure PZM21: A Biased Agonist of the Mu‐Opioid Receptor,"PZM21 ( 1 ) was recently reported as a biased agonist of the mu‐opioid receptor (MOR) with improved antinociceptive effects and reduced side effects compared with traditional opioid‐based analgesics. The original synthesis of PZM21 with the desired ( S , S ) configuration required the separation of a diastereomeric mixture in the final step by using chiral HPLC. A concise synthesis of 1 has now been developed in the enantiomeric pure form starting with commercially available l ‐alanine and proceeding via a chiral aziridine as a key intermediate. The final product was obtained as the ( S , S ) diastereomer in seven steps in 22.5 % yield from l ‐alanine. This synthetic strategy could be readily applied to the development of PZM21 analogues at the thiophenyl position.",10.1002/ejoc.201800517,2018-05-18,0.6741515270026559
Organic Process Research & Development,A Scalable Synthesis of Roxadustat (FG-4592),"A scalable five-step protocol for synthesis of roxadustat, an orally administered hypoxia-inducible factor-propyl hydroxylase inhibitor (HIF-PHI), was developed with an emphasis placed on aspects of medicinal chemistry. The isoquinoline core of the molecule was prepared using a purposefully designed cyclocondensation in which both the cyclocondensation and demasking of the groups being condensed is promoted by a common acid agent in one step. Roxadustat was obtained pure in a very competitive overall yield across all reaction steps and in compliance with permissible residual Pd level in API.",10.1021/acs.oprd.1c00281,2021-08-17,0.6741411830932741
Journal of the American Chemical Society,Rapid and Enantioselective Synthetic Approaches to Germanicol and Other Pentacyclic Triterpenes,"Two exceedingly short synthetic routes to the key intermediate 2 for the synthesis of the pentacyclic triterpene germanicol 1 have been developed. In the first, the ( S)-epoxide of farnesyl bromide is transformed in just three steps to the tetracyclic intermediate 7, which is converted to chiral 2 by treatment with polyphosphoric acid. The second synthetic route to 2 involves the coupling of the ( S)-epoxide 8 with vinyl iodide 9 to give 10 and two-stage acid-catalyzed cyclization of 10 to form 2. During the course of this work we have also discovered a very unusual intramolecular 1,5-proton shift from a carbocation to a C-C double bond. The details of the process have been confirmed by (2)H-labeling experiments.",10.1021/ja802730a,2008-06-14,0.6741338923230585
Journal of the American Chemical Society,Structure Elucidation and Enantioselective Total Synthesis of the Potent HMG-CoA Reductase Inhibitor FR901512 via Catalytic Asymmetric Nozaki−Hiyama Reactions,"The structure elucidation and enantioselective total synthesis of the potent HMG-CoA reductase inhibitor FR901512 were accomplished. FR901512 was prepared in 15 steps from the commercially available 2-bromo-4-methylbenzaldehyde via FR901516 in 16.3% overall yield (89% average yield). The catalytic asymmetric Nozaki−Hiyama reactions developed by us proved their applicability and reliability through this work, enabling the concise, efficient, and protecting-group-free enantioselective total syntheses of these new statins.",10.1021/ja070812w,2007-03-17,0.6741158850035217
Synlett,An Efficient New Synthesis of Racemic Cetiedil and a Novel Route to α-Ketocarboxylic Acids Utilising Mild Conditions,"We describe a new efficient synthesis of the prescribed racemic drug cetiedil [(±)-2-cyclohexyl-2-(3-thienyl)ethanoic acid 2-(hexahydro-1H-azepin-1-yl)ethylester]. Additionally, we report herein a high yielding large scale, route to its acid precursor 7, subsequently enabling large-scale synthesis of the chiral forms of cetiedil, and detailed pharmacological investigations.",10.1055/s-2007-977414,2007-04-03,0.6740892258124995
Synthesis,Protecting-Group-Free Total Synthesis of 8-Methoxygoniodiol,"A concise stereoselective total synthesis of the naturally occurring styryl lactone 8-methoxygoniodiol in five simple steps from readily available inexpensive trans -cinnamaldehyde is described. The efficient synthesis features a successful protecting-group-free strategy, with desirable step- and atom-economy. The synthetic strategy relies on a Maruoka asymmetric allylation, an epoxidation, a ring-closing metathesis, and a stereoselective epoxide ring opening as key steps.",10.1055/s-0035-1561491,2016-07-21,0.6740434120117083
Synthesis,"<i>exo</i>-2-Oxazolidinone Dienes in the Total Synthesis of the Natural Carbazoles, 6-Methoxymurrayanine and Clausenine","A new application of exo-2-oxazolidinone dienes in the regioselective synthesis of natural carbazoles, 6-methoxymurrayanine (6) and clausenine (7), is described. The regioselective cycloaddition of novel diene 10 to acrolein by Lewis acid catalysis provided adduct 12, which after aromatization gave benzoxazolone 14 as the key intermediate for the preparation of both carbazoles. A straightforward and efficient synthesis of 7 was carried out by a procedure with no isolation of intermediates, starting from 14 and went through a sequence of hydrogenation-hydrolysis-methylation and Pd-cyclization to give the desired carbazole 7 in high overall yield.",10.1055/s-2007-983741,2007-06-26,0.6740412523848232
Synlett,A Synthesis of the C24-C34 Segment of FK 506,All articles of this category A practical route to the C24-C34 segment of FK 506 via ( R )-(+)-3-cyclohexene-1-carboxylic acid ( 5 ). Key steps in the synthesis include asymmetric Diels-Alder and aldol reactions and enantioselective hydrolysis of a diester catalysed by pig liver esterase.,10.1055/s-1990-20978,1990-01-01,0.6740192504243695
Tetrahedron,"An efficient stereoselective synthesis of Z-(2S)- and Z-(2R)-2-tert-butoxycarbonylamino-6-hydroxyhex-4-enoic acid, key intermediates in the synthesis of (2S,4S,5R)-(−)- and (2R,4R,5S)-(+)-bulgecinine",,10.1016/s0040-4039(01)02338-3,2002-02-01,0.6740011596833146
Organic Process Research & Development,Leveraging High-Throughput Experimentation to Drive Pharmaceutical Route Invention: A Four-Step Commercial Synthesis of Branebrutinib (BMS-986195),"The invention of a commercial route to the Bruton's tyrosine kinase inhibitor branebrutinib (BMS-986195) in four total chemical steps is described. The execution of high-throughput experimentation (HTE) coupled with a first-principles approach across the proposed synthetic route enabled the identification of a novel indolization reaction that rapidly generated high synthetic complexity, as the centerpiece of the synthesis. A parallel HTE strategy during route design enabled the efficient and rapid evaluation of multiple options within a short timeframe to complete rigorous process development while mitigating the risks associated with implementing new chemistry featuring an aggressive disconnection strategy.",10.1021/acs.oprd.1c00443,2022-02-15,0.6739660647336334
Organic Process Research & Development,Asymmetric Synthesis of a TRPV1 Antagonist via <i>tert</i>-Butanesulfinamide-Directed Reductive Amination with a Chromanone,"An expedient asymmetric synthesis of TRPV1 antagonist 1 has been developed and demonstrated on multikilogram scale. The enabling route to 1 is detailed herein and characterized by the following key transformations: an aldol-cyclodehydration sequence to install the chromanone, and an auxiliary-mediated diastereoselective reductive amination.",10.1021/op400184f,2014-01-10,0.6739559962655451
Tetrahedron,Nucleosides and nucleotides. 159. Synthesis of thietane nucleosides via the Pummerer reaction as a key step,,10.1016/0040-4039(96)01719-4,1996-10-01,0.673911655854797
Journal of Organic Chemistry,A New Synthetic Route to (North)-Methanocarba Nucleosides Designed as A<sub>3</sub> Adenosine Receptor Agonists,"Activation of the A3 adenosine receptor (AR) is associated with cerebroprotective, cardioprotective, and anticancer effects. Among potent and selective A3 AR agonists are novel methanocarba adenosine analogues in which the conformation of a pseudo-ribose moiety is locked in the North (N) hemisphere of the pseudorotational cycle. 5'-Uronamide (N)-methanocarba nucleosides, such as MRS1898 and MRS2346, are examples of full agonists of the human A3 AR. An improved convergent approach from easily accessible 2,3-O-isopropylidene-d-erythrose (2b), and the combination of a strategic intramolecular cyclopropanation step plus the acid-catalyzed isomerization of an isopropylidene group, provided a suitable pseudosugar precursor (23) for the synthesis of MRS1898, MRS2346, and related analogues. This new synthetic route uses readily available building blocks and opens the way for the preparation of a variety of targets on a reasonable scale.",10.1021/jo0487606,2004-11-24,0.6739035180457582
Tetrahedron,"An asymmetric dihydroxylation route to (2S,3S)-3-hydroxypipecolic acid",,10.1016/j.tetlet.2004.09.123,2004-10-05,0.6738755783688002
Organic Letters,Synthetic Route to Chiral Tetrahydroquinoxalines via Ring-Opening of Activated Aziridines,A highly regio- and stereoselective route for the synthesis of racemic and nonracemic tetrahydroquinoxalines via the S(N)2-type ring-opening of activated aziridines with 2-bromoanilines followed by the Pd-catalyzed intramolecular C-N bond formation is described.,10.1021/ol2023906,2011-10-17,0.6738658455792553
Organic Process Research & Development,"A Practical Synthesis of a Diazepinylbenzoic Acid, a Retinoid X Receptor Antagonist","An optimized convergent synthetic route for the preparation of retinoid X receptor (RXR) antagonist ( 1 ) in an overall yield of 35% is described. The formation of the benzodiazepine was achieved in 85% yield using POCl 3 in toluene. The drug substance 14 was obtained by treatment of aryl bromide with vinyl butyl ether in the presence of palladium acetate, DPPP, and cesium carbonate This one-pot operation incorporating three chemical transformations (i.e., Heck reaction, hydrolysis of vinyl ether, and hydrolysis of ester) was achieved in 85% yield.",10.1021/op800142b,2008-09-23,0.6738495852768248
Tetrahedron,Synthesis of the taxane diterpenes: Construction of a bc ring intermediate for taxane synthesis,,10.1016/s0040-4039(01)91171-2,1984-01-01,0.6738373559960106
Synthesis,An Efficient Synthesis of 3′-Azido-3′-deoxythymidine (AZT),"All articles of this category A very efficient synthesis of 3′-azido-3′-deoxythymidine ( 4 ) (AZT) from thymidine is described. The key step is a one-pot transformation of thymidine into 2,3′-anhydro-5′- O -(4-methoxybenzoyl)-thymidine ( 2 ) which is isolated by direct crystallization. Further ring opening of 2 with the azide ion and 5′- O -deprotection afforded AZT in 73 % overall yield.",10.1055/s-1991-26434,1991-01-01,0.6737580144888409
Journal of Organic Chemistry,Studies for the Total Synthesis of Amphidinolide P,"A convergent, enantiocontrolled total synthesis of the 15-membered macrolide, amphidinolide P, is described. The synthesis utilizes three nonracemic components for an efficient assembly of the macrolactone in 12 steps via the longest linear pathway. Key developments include studies of the Hosomi-Sakurai reaction for the formation of the C6-C7 bond, a ""ligandless"" palladium-mediated Stille cross-coupling of the vinylic stannane 4 and the alkenyl bromide 5 to produce a highly functionalized dienol, and a thermally induced, intramolecular lactonization via the late-stage formation of an intermediate α-acylketene.",10.1021/jo4002382,2013-04-16,0.6737398802764797
Tetrahedron,"Development of N6-methyl-2-(1,2,3-triazol-1-yl)-2′-deoxyadenosine as a novel fluorophore and its application in nucleotide synthesis",,10.1016/j.tetlet.2016.02.003,2016-02-02,0.6737336095806409
Synthesis,"Efficient Synthesis of 2,2,4,4,6,6-Hexanitroadamantane under Mild Conditions","Two strategies have been developed for the synthesis of 2,2,4,4,6,6-hexanitroadamantane (HNA). Both strategies used the readily available diethyl malonate and paraformaldehyde as the starting materials, and utilized acylation followed by intramolecular aldol condensation to construct the adamantane skeleton. The clean nitration to introduce the gem -dinitro groups onto the adamantane skeleton was conducted using dinitrogen pentoxide in refluxing dichloromethane in the presence of urea and 4 Å molecular sieves. The acetylation route was accomplished via 12 steps and afforded HNA in an overall yield of 4.7%, and the formylation route was achieved via 11 steps in 14% overall yield.",10.1055/s-0033-1341251,2014-05-13,0.6737237213952472
Organic Process Research & Development,Early Process Development and Scale-Up of a Positive Allosteric Modulator of the α7 Nicotinic Acetylcholine Receptor,"A practical and efficient process was developed for the manufacture of a positive allosteric modulator (PAM) of the α7 nicotinic acetylcholine receptor via an eight-step synthetic route that furnished a high-quality active pharmaceutical ingredient. Highlights of this synthesis include (1) a highly reproducible palladium-catalyzed cyanation; (2) reduction in the number of steps by revisiting the original protection/deprotection strategy; (3) avoidance of the use of halogenated solvents in all of the steps; (4) replacement of reagents that had procurement issues, such as N -phenyltrifluoromethanesulfonimide and Ghosez’s reagent, with more commonly used reagents; and (5) no chromatographic purification in any step. This highly efficient process was successfully demonstrated on a pilot scale to yield up to 63.5 kg of the active pharmaceutical ingredient.",10.1021/acs.oprd.3c00317,2024-02-07,0.673704975446192
Organic Letters,Stereoselective Total Synthesis of <i>ent</i>-EI-1941-2 and Epi-<i>ent</i>-EI-1941-2,"The first asymmetric total syntheses of ent-EI-1941-2 and epi-ent-EI-1941-2 have been accomplished, starting from a chiral epoxy iodoquinone 6, a key intermediate in our total syntheses of epoxyquinols A and B. A key step in the preparation of ent-EI-1941-2 is an intramolecular carboxypalladation via a 6-endo cyclization mode, followed by beta-hydride elimination, while carboxymercuration is a key step in the synthesis of epi-ent-EI-1941-2. [reaction: see text]",10.1021/ol0481479,2004-10-23,0.6736963796922372
Journal of Organic Chemistry,An Alternative Synthetic Route to Rilzabrutinib via an E-Configured Cyanoacrylic Acid Intermediate,"In this manuscript, an alternative route of synthesis for making rilzabrutinib via amide formation was described. The two segments for the amide formation are pyrazolopyrimidine-piperidine 20 and E-cyanoacrylic acid 21 . The yield of 20 from Mitsunobu reaction was doubled compared with the existing route, and the Knoevenagel-derived 21 exhibited exclusive E-configuration. This route, in contrast to Sanofi’s medicinal chemistry route, avoids Z/E isomer separation, achieves a 20-fold increase in overall yield, and improves sustainability through transition-metal-free catalysis and chromatography-free intermediates purification.",10.1021/acs.joc.5c02058,2025-10-11,0.6736779570975799
Tetrahedron,"A practical stereoselective synthesis of (2S, 3S)-3-hydroxyleucine","A practical and convenient procedure is described for the preparation of gram quantities of (2S, 3S)-3-hydroxyleucine. The key step involves the triflatemediated cyclization of spirooxazolidine 4 to the spirobicyclic compound 5, which is easily converted to the title compound in high yield.",10.1016/0040-4039(95)01456-r,1995-09-01,0.6736052450837663
Journal of Organic Chemistry,Synthesis of Cyclopentanyl Carbocyclic 5-Fluorocytosine ((−)-5-Fluorocarbodine) Using a Facially Selective Hydrogenation Approach,"An efficient synthetic route to biologically relevant (-)-5-fluorocarbodine 6 was developed. Direct coupling of N(6)-protected 5-fluorouracil 15 with cyclopentenyl intermediate 13, followed by formation of a macrocycle between the base and the carbocyclic sugar moiety, via ring-closing metathesis, allowed for a facial selective hydrogenation of the sugar double bond to give, exclusively, the desired 4'-β stereoisomer.",10.1021/jo302038d,2012-12-10,0.6736051290427126
Organic Letters,"Total Synthesis of Valerenic Acid, a Potent GABA<sub>A</sub>Receptor Modulator","The first total synthesis of the sesquiterpenoid valerenic acid, a constituent of Valeriana officinalis, is described. The compound is a potent modulator of the GABA(A) receptor and may thus be useful in the treatment of various dysfunctions of the central nervous system. The synthesis is enantio-, diastereo-, and regiocontrolled and utilizes an enyne-RCM, a metal-coordinated Diels-Alder reaction, a hydroxy-directed Crabtree hydrogenation, and a Negishi methylation as key steps.",10.1021/ol9000137,2009-01-29,0.6736004164172003
Tetrahedron,Synthesis of RWJ 68354: A potent inhibitor of the MAP kinase p38,,10.1016/s0040-4039(98)01991-1,1998-11-01,0.6735712609064373
European Journal of Organic Chemistry,Synthesis of the Altertoxin I Framework,"Abstract Routes to the framework of perylenequinone‐derived mycotoxins of the biphenyl type are described. 1,2,11,12‐Tetrahydroperylenequinone is most suitably prepared in seven steps starting with 3‐hydroxyacetophenone. Key steps are an Ullmann coupling, pinacol‐type cyclization, bromination, enolate reaction, and intramolecular Friedel‐Crafts cyclization. A second approach starting with 1,5‐dihydroxynaphthalene yields the respective decarbonylated core. Key steps of this 5‐step sequence are again an Ullmann coupling and a McMurry olefination. The cleavage of the preferentially utilized hexyl protecting group could be achieved with boron bromide.",10.1002/ejoc.202301052,2023-11-21,0.6735577638838064
Organic Process Research & Development,"Commercial Route Development of Sigma-2 Receptor Modulator, CT1812 Leveraging Photoflow, and HTS Technologies","A second-generation synthesis of CT1812, a sigma-2 receptor modulator (ligand), was developed from readily available starting materials to support late-stage clinical needs. An AIBN-induced thermal benzylic bromination in DCE was replaced by a visible-light-induced continuous flow process in MeCN operating at room temperature. High throughput screening was employed to overcome the unexpected challenges encountered in the hydrogenation of alkyne 13 in the penultimate step. The rationale for a polymorph switch from the originally developed monofumarate anhydrate to the more thermodynamically stable hemifumarate dihydrate is also described. The new convergent route proceeds in eight steps (longest linear sequence (LLS) = 6) as compared to the original med chem route (12 steps; LLS = 9) and has been successfully demonstrated on a 100 kg scale.",10.1021/acs.oprd.4c00412,2025-01-29,0.6735395995988019
Organic Letters,"A Simple, Scalable Synthetic Route to (+)- and (−)-Pseudoephenamine","A three-step synthesis of pseudoephenamine suitable for preparing multigram amounts of both enantiomers of the auxiliary from the inexpensive starting material benzil is described. The sequence involves synthesis of the crystalline monomethylimine derivative of benzil, reduction of that substance with lithium aluminum hydride, and resolution of pseudoephenamine with mandelic acid.",10.1021/ol402815d,2013-10-18,0.6735107830928974
Organic Letters,Enantioselective Synthesis of Spliceostatin G and Evaluation of Bioactivity of Spliceostatin G and Its Methyl Ester,"An enantioselective total synthesis of spliceostatin G has been accomplished. The synthesis involved a Suzuki cross-coupling reaction as a key step. The functionalized tetrahydropyran ring was constructed from commercially available optically active tri-O-acetyl-d-glucal. Other key reactions include a highly stereoselective Claisen rearrangement, a Cu(I)-mediated 1,4 addition of MeLi to install the C8 methyl group, and a reductive amination to incorporate the C10 amine functionality of spliceostatin G. Biological evaluation of synthetic spliceostatin G and its methyl ester revealed that it does not inhibit splicing in vitro.",10.1021/acs.orglett.7b03456,2017-12-08,0.6735012592077914
Organic Process Research & Development,Development of a Practical and Reliable Synthesis of Laquinimod,"Laquinimod (5-chloro-1,2-dihydro- N -ethyl-4-hydroxy-1-methyl-2-oxo- N -phenyl-3-quinoline carboxamide) is a drug candidate for treatment of Multiple Sclerosis. A short and industrially feasible process for the preparation of laquinimod starting from 2-amino-6-chlorobenzoic acid, in essentially four steps, is dis-cussed. The key step is a novel reaction in which a methyl ester is converted to an amide in very high yield and with excellent purity. The present article elucidates the scale-up process along with safety aspects and the impurity profiles of the intermediates and product. Initial laboratory conditions are described as well as the changes made on transfer to pilot-plant scale.",10.1021/op700001c,2007-06-30,0.6734936010093929
Journal of Organic Chemistry,"Palladium-Catalyzed Intramolecular Allylic Alkylation Reaction in Marine Natural Product Synthesis:  Enantioselective Synthesis of (+)-Methyl Pederate, a Key Intermediate in Syntheses of Mycalamides","A novel preparation of (+)-methyl pederate (4), a key intermediate in syntheses of mycalamides (1), marine natural products from a New Zealand sponge of the genus Mycale, is described. The key step involves palladium-catalyzed intramolecular allylic alkylation of the carbonate 21, derived from (+)-(4R,5R,E)-5-(tert-butyldimethylsiloxy)-4-methyl-2-hexenol (13), yielding lactones 5 in 87% yield. Demethoxycarbonylation of the cyclization products 5 and further functional group transformations led to (+)-methyl pederate (4).",10.1021/jo9805246,1998-07-30,0.6734905053145902
Organic Process Research & Development,"Design, Development, and Scale-Up of a Stereoselective Synthesis of (1<i>R</i>,3<i>R</i>)-3-(3,5-Bis(trifluoromethyl)phenyl)-2,2-dichlorocyclopropane Carboxylic Acid","This report describes the design, development, and scale-up of a stereoselective synthesis of (1 R,3 R )-3-(3,5-bis(trifluoromethyl)phenyl)-2,2-dichlorocyclopropane carboxylic acid ( 1), a key intermediate toward the synthesis of a promising developmental agrochemical. The synthesis features d -mannitol as a sustainable chiral pool starting material, a double Heck coupling reaction, and the invention of diastereoselective dichlorocyclopropanation. Details disclosed include the route design, development of enabling steps, and learnings from a kilogram-scale campaign. The nine-step route was used to produce 1.5 kg of (1 R,3 R )-3-(3,5-bis(trifluoromethyl)phenyl)-2,2-dichlorocyclopropane carboxylic acid in 13% overall yield, 97.8% purity, and excellent enantiopurity (>99.5% ee) .",10.1021/acs.oprd.4c00425,2024-12-20,0.6734853696197469
Synlett,"A Short and Efficient Synthesis of 1,5-Dideoxy-1,5-imino-d-galactitol (1-deoxy-d-Galactostatin) and 1,5-Dideoxy-1,5-imino-l-altritol (1-deoxy-l-Altrostatin) from d-Galactose",All articles of this category A short and efficient route is described for the synthesis of 1-deoxy-d-galactostatin and 1-deoxy-l-altrostatin starting from d-galactose. galactostatin - altrostatin - azasugars - galactose - triflation,10.1055/s-1999-3158,1999-05-01,0.673479613842577
Synthesis,Synthesis of Aculeatins A and B via Iterative Hydrolytic Kinetic Resolution,A simple and concise approach for the synthesis of aculeatins­ A and B starting from (±)-epichlorohydrin is described. The synthetic strategy features Jacobsen’s hydrolytic kinetic resolution and a Linchpin coupling as key steps.,10.1055/s-0029-1218687,2010-02-24,0.6734449114230748
Tetrahedron,Efficient synthesis of (Z)- and (E)-methyl 2-(methoxyimino)-2-phenylacetate,,10.1016/j.tetlet.2010.02.073,2010-02-20,0.6734384852814629
Organic Letters,Synthesis of a Novel UDP-carbasugar as UDP-galactopyranose Mutase Inhibitor,"The multistep synthesis of a novel UDP-C-cyclohexene, designed as a high energy intermediate analogue of the UDP-galactopyranose mutase (UGM) catalyzed isomerization reaction, is reported. The synthesis of the central carbasugar involved the preparation of a galactitol derivative bearing two olefins necessary for the construction of the cyclohexene ring by a ring-closing metathesis as a key step. Further successive phosphonylation, deprotection, and UMP coupling provided the target molecule. The final molecule was assayed against UGM and compared with UDP-C-Galf, the C-glycosidic UGM substrate analogue.",10.1021/ol500848q,2014-04-18,0.6734333175657821
Journal of Organic Chemistry,"Diastereoselective Formal Synthesis of a Monoterpene Alkaloid, (−)-Incarvilline","Diastereoselective formal synthesis of a monoterpene alkaloid, (-)-incarvilline, the key intermediate for the synthesis of (-)-incarvillateine, was achieved by using an intramolecular Pauson-Khand reaction of (S)-N-[(E)-2-butenyl]-N-(3-butynyl-2-methoxymethoxy)-p-toluenesulfonamide as a key step.",10.1021/jo0709091,2007-07-21,0.6734170381211003
Organic Letters,Total Synthesis of (−)-Exiguolide,"A concise total synthesis of (-)-exiguolide has been completed in an overall 2.8% yield over 20 steps in the longest linear path. The key strategies involve (1) Prins cyclization/homobromination of dienyl alcohol with the B ring-substituted aldehyde, prepared by Prins cyclization/bromination, to construct the A ring with excellent cis-Z stereochemical control and (2) an unusual side chain installation/macrocyclization strategy featuring Sonogashira cross-coupling followed by a ring-closing metathesis reaction to deliver the target.",10.1021/acs.orglett.5b02162,2015-09-15,0.6733763815636242
Journal of Organic Chemistry,"Enantioconvergent Synthesis of (−)-(<i>2R</i>,5<i>S</i>)-1-Allyl-2,5-dimethylpiperazine, an Intermediate to δ-Opioid Receptor Ligands","A convenient, high-yield enantioconvergent synthesis of (-)-1-allyl-(2S,5R)-dimethylpiperazine from trans-2,5-dimethylpiperazine has been developed. This compound is an important intermediate in the synthesis of delta-opioid receptor ligands. The process allows for the laboratory preparation of 100 g quantities of this enantiomerically pure diamine without chromatography. The key steps in the sequence were an efficient optical resolution using relatively inexpensive resolving agents, followed by interconversion of the unwanted (+)-enantiomer into the desired (-)-enantiomer.",10.1021/jo0300385,2003-04-23,0.6733686412265345
Organic Letters,Regioselective Pd-Catalyzed Synthesis and Application of 3-Methyl-5-bromo-2-pyrone toward Keto-phomactin A,"[Structure: see text] An efficient one-step synthetic protocol for 3-methyl-5-bromo-2-pyrone was developed using the C3-selective Pd-catalyzed coupling reaction of 3,5-dibromo-2-pyrone with Me3Al-dimethylaminoethanol complex. A subsequent seven-step reaction sequence provided a cyclohexenyl bromide, which served as the key intermediate for the synthesis of the keto analogue of phomactin A, in 31% overall yield.",10.1021/ol061231z,2006-06-30,0.6733278623965374
Journal of the American Chemical Society,Biomimetic Asymmetric Total Synthesis of (−)-Laurefucin via an Organoselenium-Mediated Intramolecular Hydroxyetherification,"The first asymmetric total synthesis of (-)-laurefucin (1), a unique C-15 acetogenin with a 2,8-dioxabicyclo[5.2.1]decane skeleton, has been accomplished in nine steps in 31% overall yield from known oxocene 10. Highlights of the highly stereoselective synthesis include a novel organoselenium-mediated biomimetic hydroxyetherification.",10.1021/ja806304s,2008-11-17,0.6733174667961561
Organic Letters,Enantioselective Syntheses of (<i>S</i>)-Ketamine and (<i>S</i>)-Norketamine,"An efficient asymmetric synthesis of ( S )-ketamine (esketamine) based on catalytic enantioselective transfer hydrogenation of cyclic enone and [3,3]-sigmatropic rearrangement of allylic cyanate to isocyanate is described. The catalytic asymmetric route afforded esketamine (99.9% ee) in 50% overall yield over four steps and forms the basis for the future development of the drug substance. Furthermore, the route was applicable to the synthesis of ( S )-norketamine via simple hydrolysis of isocyanate penultimate.",10.1021/acs.orglett.9b02575,2019-08-08,0.6732862341385351
Organic Process Research & Development,Development of a Potential Manufacturing Route to PF-00610355: A Novel Inhaled β<sub>2</sub>-Adrenoreceptor Agonist,"The development of a practical, scalable route to PF-00610355 ( 8 ) is described. In this convergent approach, amine 9 is coupled to protected bromohydrin 1 to give the doubly protected intermediate 26 . TBS-Deprotection of 26 affords the benzyl protected penultimate intermediate 25 which is crystallized as the corresponding hemifumarate salt 25a . On the basis of solubility data, the final debenzylation was conducted in aqueous THF, and the API ( 8 ) is isolated from acetonitrile by an unusual distillative crystallization process. The development of an efficient process to prepare amine 9 is also described.",10.1021/op2002408,2011-09-30,0.6732044611104043
Organic Process Research & Development,Process Development for the Synthesis of <b>BI 1702135</b>: A Concise Design Enabled by Selective Acylation of a 2-Aminobenzimidazole Intermediate,The route design and process development for the synthesis of BI 1702135 are described. The synthetic design centers around an amide synthesis involving a 2-amino benzimidazole analog 4 that has two competing acylation sites. A highly selective acylation protocol at the desired N-2′ site was identified. Robust and convenient processes were developed for each step in this five-step synthesis of BI 1702135 .,10.1021/acs.oprd.3c00050,2023-04-05,0.6731959418983136
Tetrahedron,A novel and practical synthesis of polycyclic fluoranthenes,,10.1016/0040-4039(95)00314-3,1995-04-01,0.673192349526848
Tetrahedron,A novel and practical synthesis of 2-benzoylbenzothiazoles and 2-benzylbenzothiazoles,,10.1016/j.tetlet.2010.12.057,2010-12-23,0.673192349526848
Tetrahedron,Novel practical synthesis of d-cycloserine,,10.1016/j.tetlet.2012.05.120,2012-06-07,0.673192349526848
European Journal of Organic Chemistry,"A Common Synthetic Protocol for the Cyclic and Acyclic Core of Migrastatin, Isomigrastatin, and Dorrigocin via a Chiral β‐Hydroxy‐γ‐butyrolactone Intermediate","Abstract A facile synthetic route has been developed for the synthesis of the cyclic and acyclic cores of migrastatin, isomigrastatin, and dorrigocin. The common synthetic route goes via a β‐hydroxy‐γ‐butyrolactone intermediate that is obtained by a Pd II ‐catalysed asymmetric allylic intramolecular cyclization of 3‐hydroxy‐2‐methylhex‐5‐enoic acid following a protocol developed by White and coworkers.",10.1002/ejoc.201402830,2014-08-26,0.6731921479923362
Organic Letters,"Synthesis of a 3,4,5-Trimethoxybenzoyl Ester Analogue of Epigallocatechin-3-gallate (EGCG):  A Potential Route to the Natural Product Green Tea Catechin, EGCG","The synthesis of a trimethoxybenzoyl ester (D-ring) analogue of epigallocatechin-3-gallate (EGCG) is described. The versatile synthesis route can be used to synthesize A, B, and D ring analogues of EGCG and involves a key cyclization of the chalcone to the 3-flavene. This synthesis provides a possible route to the polyphenolic green tea natural product EGCG.",10.1021/ol007000o,2001-02-16,0.6731518411091633
Tetrahedron,Template synthesis of a cryptand with hetero-ditopic receptor sites,,10.1016/s0040-4039(00)60830-4,1992-01-01,0.6731360419172606
Tetrahedron,Flexible synthetic route to 6-deoxy and 11-deoxyanthracyclinones,,10.1016/s0040-4039(01)80922-9,1985-01-01,0.6731076530995032
Journal of Organic Chemistry,"Preparation of Methyltriazolo[1,4]benzodiazepine via Oxidative Activation of a Thiolactam for the Synthesis of BET Inhibitor Molibresib","A novel oxidative activation of a thiolactam was developed for the preparation of methyltriazolo[1,4]benzodiazepine in a single step. A sulfenic acid (R-SOH) was proposed as the activated intermediate with the concurrent formation of acetylhydrazone from acethydrazide and cyclocondensation to the triazole. A version of the method with 35% peracetic acid was scaled up to 40 kg as a part of the new route for the synthesis of BET inhibitor molibresib (GSK525762). The thiolactam was prepared from commercially available (2-amino-5-methoxyphenyl)(4-chlorophenyl)methanone in two steps in 66% yield. The concise four-step synthesis delivered 52 kg of molibresib of >99.9% ee in an overall 41% yield from the ketone. The condition for the methyltriazole was mild and free of racemization of the sensitive stereocenter. The oxidative method, with several advantages to the known methods, should be applicable to the synthesis of alkyltriazoles from other thiolactams and acylhydrazines.",10.1021/acs.joc.1c00563,2021-04-20,0.6731029536723888
Journal of Organic Chemistry,Total Synthesis of (+)-Himbacine and (+)-Himbeline,"Himbacine ( 1 ), a complex piperidine alkaloid isolated from the bark of Australian magnolias, is a promising lead in Alzheimer's disease research due to its potent muscarinic receptor antagonist property. We have described here a highly efficient synthetic strategy that resulted in the total synthesis of himbacine ( 1 ) in about 10% overall yield and isohimbacine ( 1a ), an unnatural isomer of himbacine, in 18% overall yield. The total synthesis of himbacine was initially approached using an intramolecular Diels−Alder reaction as the key step to generate intermediate 5 followed by a [3 + 2] cycloaddition with nitrone 4 to produce the isoxazolidine derivative 3 . Methylation followed by catalytic reduction of 3 gave 12‘-hydroxyhimbacine ( 20 ), which, upon dehydration, gave isohimbacine ( 1a ) as the sole product. In an alternative approach, an all-encompassing intramolecular Diels−Alder reaction of an appropriately substituted tetraene derivative 31, which bears the entire latent carbon framework and functional group substitution of himbacine, gave the desired advanced tricyclic intermediate 33, which was readily converted to (+)-himbeline ( 2 ) and (+)-himbacine ( 1 ).",10.1021/jo981983+,1999-02-23,0.6730101169528718
Organic Process Research & Development,Development of a Multikilogram Scale Synthesis of a TRPV1 Antagonist,"A highly efficient, regioselective five-step synthesis of the TRPV1 antagonist 1 is described. The coupling of piperazine 7 with dichloropyrimidine 8 proceeded via a regioselective Pd-mediated amination affording product 11 in excellent yield. Conversion of the penultimate product 14 afforded 1 through formation of a magnesium ate complex and trapping with CO 2 .",10.1021/acs.oprd.5b00388,2016-01-13,0.6730006813727559
Synlett,"Synthetic Studies of Halichondrin B, an Antitumor Polyether Macrolide Isolated from a Marine Sponge. 2. Efficient Synthesis of C16-C26 Fragments<i>via</i>Construction of the D Ring by a Highly Stereocontrolled Iodoetherification",All articles of this category A stereoselective synthesis of C16-C26 fragments of halichondrin B starting from D-malic acid and methyl (2 S )-3-hydroxy-2-methylpropionate using iodoetherification for an efficient construction of the D ring as the key step is described.,10.1055/s-1994-22731,1994-01-01,0.6729874299991853
Organic Process Research & Development,"A New Efficient Synthetic Route for the Synthesis of the Antiallergic Drug, Olopatadine Hydrochloride, via Stereospecific Palladium-Catalyzed Reaction","A new practical and efficient synthetic route for the synthesis of olopatadine hydrochloride via the intramolecular stereospecific seven-membered ring cyclization from an alkyne intermediate using palladium catalyst and hydride source was established. Furthermore, the optimization of that key stereospecific reaction was examined by design of experiment (DoE), and the desired Z -isomer could be obtained with high yield.",10.1021/op200312m,2011-12-22,0.6729384043300748
Journal of Organic Chemistry,Improved Synthesis of the A−G Ring Segment of Brevetoxin B,"An efficient synthesis of the A-G ring segment 2, a key intermediate for the total synthesis of brevetoxin B (1), was achieved in 37 steps and 5.0% overall yield. The intramolecular allylation of the O,S-acetal 22, prepared from the ABC ring segment 15 and the FG ring segment 17, was carried out using AgOTf as a Lewis acid to give the desired compound 23, predominantly. Ring-closing metathesis of 23 with the Grubbs catalyst 12 afforded the heptacyclic ether 25. Selective hydrogenation of the E ring olefin of 25 was performed by diimide reduction to afford 2.",10.1021/jo0603025,2006-04-11,0.6729108290927236
Journal of Organic Chemistry,Straightforward Stereoselective Access to Cyclic Peptidomimetics,"The preparation of cyclic dipeptide mimetics from chiral imino lactones derived from (R)-phenylglycinol is described. Key steps of the synthetic route included the fully stereoselective construction of a quaternary center, the formation of six-, seven-, or eight-membered lactams by means of an RCM cyclization, and the introduction of a new amino group within the lactam ring. The synthesis of a tripeptide mimetic is also reported.",10.1021/jo900679c,2009-05-13,0.6729025671134301
Organic Process Research & Development,Catalyst-Free Cyclization- and Curtius Rearrangement-Induced Functional Group Transformation: An Improved Synthetic Strategy of First-in-Class ATX Inhibitor Ziritaxestat (GLPG-1690),"A practical and highly efficient protocol for the production of Autotaxin (ATX) inhibitor Ziritaxestat ( 1 ) was described. The procedure began with a catalyst-free bicomponent cyclization for the construction of the imidazo[1,2- a ]pyridine skeleton 16 . Subsequently, a typical Curtius rearrangement of carboxylic acid 17 followed by nucleophilic attacking of 3,5-dichlorobenzyl alcohol 18f led to the carbamate analogue 19f . N -methylated 20 was readily deprotected through HBr/HOAc treatment, which further conveniently took part in an alternative K 2 CO 3 -induced N -alkylation reaction with 9 to give 10 . 10 coupled directly with piperazine to furnish 13, which ideally circumvent the removal of the Boc group. As a result, the hypertoxic KCN and the hypertoxic and costly isonitrile 3 involved in the tricomponent cyclization were carefully avoided. Ultimately, a novel, scalable, and cost-effective route was favorably developed to afford Ziritaxestat in a 20.4% overall yield.",10.1021/acs.oprd.9b00511,2020-04-23,0.6728810541721416
Journal of Organic Chemistry,"Synthetic Studies on Enantioselective Total Synthesis of Cyathane Diterpenoids: Cyrneines A and B, Glaucopine C, and (+)-Allocyathin B<sub>2</sub>","The details for the synthetic studies on enantioselective total synthesis of cyathane diterpenoids cyrneine A ( 1 ) and B ( 2 ), glaucopine C ( 3 ), and (+)-allocyathin B 2 are presented. We established a mild Suzuki coupling for heavily substituted nonactivated cyclopentenyl triflates using a phosphinamide-derived palladacycle as precatalyst and a chelation-controlled highly regioselective Friedel–Crafts cyclization. The utilization of these two key reactions enabled a rapid construction of the 5-6-6 tricyclic skeleton. In the middle stage of the synthesis, a Birch reductive methylation, a modified Wolff–Kishner–Huang reduction, and a carbenoid-mediated ring expansion were employed as the key reactions to furnish the 5-6-7 tricyclic core bearing two antiorientated all-carbon quaternary stereocenters at the C 6 and C 9 ring junctions. By applying these key transformations, a more efficient total synthesis of cyrneine A and allocyathin B 2, and the first total synthesis of cyrneine B and glaucopine C, were accomplished through a collective manner. The late-stage conversions involving a base-mediated double bond migration and a double bond migration/aerobic γ-CH oxidation cascade for the stereoselective synthesis of cyrneine B and glaucopine C were interesting.",10.1021/acs.joc.8b03138,2019-02-22,0.6728651172056994
Tetrahedron,New synthetic methodology for ring expansion of n-sized conjugated cycloalkenones into homoallylic n+3 lactones: 3-step synthesis of fragrant phoracantholide,,10.1016/s0040-4039(00)01739-1,2000-12-01,0.672838507019592
Organic Process Research & Development,Development of a Practical Synthesis of Functionalized Azaxanthene-Derived Nonsteroidal Glucocorticoid Receptor Modulators,"An efficient route to two functionalized 2-aryl-5 H -chromeno[2,3- b ]pyridines (azaxanthenes) is reported. The addition of lithiated 2,6-dichloropyridine to salicylaldehyde followed by cyclization was a key process improvement identified for the formation of the azaxanthene core. Further elaboration of 2-chloro-5 H -chromeno[2,3- b ]pyridin-5-ol at the 5 position was accomplished via Lewis acid-catalyzed coupling with commercially available ((1-methoxy-2-methylprop-1-en-1-yl)oxy)trimethylsilane. A partial classical resolution coupled with a preparative chiral supercritical fluid chromatography (SFC) separation was used to isolate the desired enantiomer of the azaxanthene carboxylic acid that is a common intermediate for both compounds 1 and 2 . Suzuki–Miyaura cross-coupling with appropriately substituted boronic acids, followed by condensation with 2-amino-1,3,4-thiadiazole, provided the target compounds with an overall yield of approximately 10%. The use of stable, amorphous materials to support clinical comparison of functionalized azaxanthenes 1 and 2 is also discussed.",10.1021/acs.oprd.6b00035,2016-04-26,0.6727879984743611
Tetrahedron,A novel synthesis of 3-cyanoindoles and a new route to indole-3-carboxylic acid derivatives,,10.1016/s0040-4039(00)94748-8,1985-01-01,0.6727730144123436
Journal of Organic Chemistry,"Practical Asymmetric Synthesis of (<i>S</i>)-4-Ethyl-7,8-dihydro-4-hydroxy-1<i>H</i>-pyrano[3,4-f]indolizine- 3,6,10(4<i>H</i>)-trione, a Key Intermediate for the Synthesis of Irinotecan and Other Camptothecin Analogs","A practical asymmetric synthesis of ( S ) 4-ethyl-7,8-dihydro-4-hydroxy-1 H -pyrano[3,4- f ]indolizine-3,6,10(4 H )-trione ( 1 ), a versatile intermediate for the synthesis of camptothecin analogs, was developed. Commercially available citrazinic acid is converted in four steps into the 2-chloro-6-methoxypyridine 5 . An ortho-directed metalation followed by reaction with a formamide produces an aldehyde with the required 2,3,4,6-substituted pyridine ( 6 ) with high regioselectivity. After refunctionalization of the aldehyde, the chloropyridine is converted into an ester by a facile palladium-mediated carbonylation reaction. Wittig reaction and racemic osmylation produce the diol 16 which is resolved by an efficient lipase resolution to an ee > 99%, and a one-pot recycle of the unwanted diol enantiomer was developed. A series of high-yielding oxidation and deprotection steps convert ( S )- 16 into the pyridone 25, which is then converted into 1 with an ee > 99.6%.",10.1021/jo970173f,1997-09-01,0.6727239991713934
Synthesis,"Synthesis of (<i>R</i>)-4-Oxo-5-phosphononorvaline, an<i>N</i>-Methyl-D-aspartic Acid Receptor Selective β-Keto Phosphonate","All articles of this category ( R )-4-Oxo-5-phosphononorvaline ( 1 ), a selective NMDA glutamate site antagonist, has been synthesized in four steps (overall yield = 31%) from ( R )-aspartic acid, without racemization.",10.1055/s-1994-25588,1994-01-01,0.6727177936615686
Tetrahedron,A facile synthetic route to new pyrazoloisoindolones,,10.1016/j.tetlet.2007.04.004,2007-04-07,0.6726611304107951
Journal of the American Chemical Society,Total Synthesis of (+)-Superstolide A,A convergent and highly stereocontrolled synthesis of +-superstolide A (1) has been accomplished. Key steps of this synthesis include the intramolecular Suzuki reaction of 26 and the highly diastereoselective transannular Diels-Alder cyclization of macrocyclic octaene 3.,10.1021/ja710238h,2008-02-07,0.6726469890513062
Journal of Organic Chemistry,"Efficient Total Synthesis of Pulchellalactam, a CD45 Protein Tyrosine Phosphatase Inhibitor","A new approach to a CD45 protein tyrosine phosphatase inhibitor, pulchellalactam, is described. The key step of the sequence involves addition and elimination of an enolic lactam in a single step and 70% yield, employing an organocuprate reagent. The resulting alpha,beta-unsaturated lactam could be condensed with isobutyraldehyde to produce Z-pulchellalactam or converted into siloxypyrrole, which was subjected to the BF(3) x Et(2)O-promoted coupling reaction with isobutyraldehyde to afford E-pulchellalactam after E1-cB elimination and TFA deprotection. This first total synthesis afforded Z-pulchellalactam in six steps and 32% overall yield from Boc-glycine. The same sequence of reactions could also be applied to the liquid- or solid-phase synthesis of trifunctionalized pulchellalactam derivatives.",10.1021/jo010828j,2002-05-29,0.6726461469946056
Tetrahedron,The Bohlmann–Rahtz route to functionalised pyridine scaffolds and their use in library synthesis,,10.1016/s0040-4039(03)00034-0,2003-02-01,0.6726231800235957
Journal of Organic Chemistry,"Total Syntheses of Strasseriolide A and Strasseriolide B, Potent Antimalarial Agents","We describe the convergent total syntheses of strasseriolides A and B, which are potent antimalarial agents recently isolated from an unnamed plant found in a remote region of New Zealand. Both natural products exhibited potent activity against malaria parasite, Plasmodium falciparum . The synthesis involved asymmetric syn-aldol, asymmetric alkylation, and asymmetric Johnson-Claisen rearrangement to set six of the seven chiral centers of strasseriolide B. The synthesis also highlights the formation of an 18-membered macrolactone from a diacid by using a Yamaguchi macrolactonization protocol. Other key transformations involved Grubbs’ cross-metathesis, selective 1,4-reduction, hydrostannylation reaction, and NHK coupling reaction. The convergent synthesis of strasseriolide A required 27 total synthetic steps and 16 longest linear steps from known readily available intermediates.",10.1021/acs.joc.4c01262,2024-08-09,0.6726006429347897
Journal of Organic Chemistry,Enantioselective Synthesis of (+)-Penostatin E,"The first enantioselective total synthesis of penostatin E has been accomplished. Two highly efficient and diastereoselective reactions, a Hosomi-Sakurai allylation and an intramolecular Pauson-Khand reaction, were utilized for the construction of the basic carbon framework of the target molecule as the key steps. A late-stage introduction of the side chain and a successful base-promoted elimination reaction afforded an efficient synthetic route to (+)-penostatin E.",10.1021/jo501225y,2014-07-30,0.6725758761040249
Journal of Organic Chemistry,Asymmetric Total Synthesis of (+)-Didemniserinolipid B via Achmatowicz Rearrangement/Bicycloketalization,"A new synthetic strategy was developed for the asymmetric total synthesis of (+)-didemniserinolipid B in 19 linear steps, featuring a highly efficient and enantioselective construction of 6,8-dioxabicyclo[3.2.1]octane (6,8-DOBCO) framework via a rarely explored Achmatowicz rearrangement/bicycloketalization strategy. In addition, the first total synthesis of the proposed (+)-didemniserinolipid C was accomplished with 41.6% yield in 4 steps from a common advanced intermediate 18, and a possible revised structure of (+)-didemniserinolipid C was proposed. The new convergent synthetic strategy greatly expedites the entry to the didemniserinolipids and their analogues for biological activity evaluation.",10.1021/jo501142q,2014-07-14,0.6725670318276329
Journal of Organic Chemistry,Enantioselective Approach to Securinega Alkaloids. Total Synthesis of Securinine and (−)-Norsecurinine,"The most representative securinega alkaloids have been synthesized through a new strategy involving the palladium-catalyzed enantioselective allylation of a cyclic imide, a vinylogous Mannich reaction, and a ring-closing metathesis process, as the key steps. The diastereoselectivity of the vinylogous Mannich reaction was in partial agreement with DFT theoretical calculations performed in a model system. The synthesis of (-)-norsecurine has been accomplished in nine steps from succinimide and 14% overall yield and that of securinine in 10 steps from glutarimide and 20% overall yield. Both syntheses compare favorably with those previously described. The three key transformations have been performed in a synthetically useful scale (more than 500 mg). Moreover, since the enantioselectivity was originated by a chiral phosphine ligand, the antipode of which is readily available, the same route is expected to give access to (+)-norsecurinine and virosecurinine.",10.1021/jo901059n,2009-07-24,0.6725450699723772
Tetrahedron,Short Synthetic Route to Retinoids Through Dialkylation of 3- Methyl -3-Sulfolene,,10.1016/s0040-4039(97)00459-0,1997-04-01,0.6725439512468492
Journal of Organic Chemistry,A Practical Synthesis of a COX-2-Specific Inhibitor,A number of synthetic strategies to the Cox-2 specific inhibitor 1 have been described. These studies have led to the identification of a novel pyridine construction using annulation of ketone 2 using a vinamidinium species 29 and ammonia in 97% assay yield. Three approaches to the synthesis of ketone 2 are described that allow for its preparation in large quantities in >65% overall yield from methyl 6-methylnicotinate.,10.1021/jo000870z,2000-09-19,0.6725297676635852
Journal of Organic Chemistry,Synthesis of the Purported <i>ent</i>-Pochonin J Structure Featuring a Stereoselective Oxocarbenium Allylation,"The synthesis of the alleged natural product pochonin J is presented. Key steps of this convergent synthesis include a chemoselective Wacker oxidation, and an Evans' anti-reduction of the resulting ketone. Upon ozonolysis, this intermediate undergoes a 6-exo-trig cyclization to give a hemiketal intermediate, the key oxocarbenium precursor. The construction of the α-C-glycoside subunit is highlighted by a mismatched oxocarbenium cation formation/allylation sequence. An olefin metathesis afforded the 14-membered macrolactone, and final oxidation provided the ""desired"" compound that does not spectroscopically correlate to the initially described natural product.",10.1021/jo200332d,2011-04-15,0.6724783255283996
Synlett,"Efficient Synthesis of (–)-Hanishin, (–)-Longamide B, and (–)-Longamide B Methyl Ester through Piperazinone Formation from 1,2-Cyclic Sulfamidates","We describe a simple chiral-pool synthesis of (–)-longamide B, (–)-longamide B methyl ester, and (–)-hanishin. The key feature of the total synthesis is the formation of a piperazinone from a 1,2-cyclic sulfamidate and methyl 2-pyrrolecarboxylate, which permits efficient construction of the pyrrolopiperazinone core scaffold.",10.1055/s-0035-1560988,2015-12-09,0.6724439415818353
Organic Process Research & Development,Process Research and Development of TP-808: A Key Intermediate for the Manufacture of Synthetic Tetracyclines,"Process research, development, and manufacture of TP-808 ( 1 ), a key intermediate for the discovery and manufacture of tetracycline analogues, is described. The process used for the preparation of 1 avoids chromatographic purifications and has been substantially improved over the previously reported preparation. The robustness of the process was demonstrated in a 76.1 kg manufacturing campaign with 56% overall yield.",10.1021/acs.oprd.7b00003,2017-02-10,0.6724162427424792
Synthesis,The Wender Cedrene Synthesis Revisited: A Catalytic Enantioselective Entry to the Chiral Key Intermediate,"The seminal synthesis of the sesquiterpene (±)-α-cedrene reported by Wender in 1981 offers a uniquely short and elegant access to the bridged-tricyclic target compound by exploiting an intramolecular arene-olefin photocycloaddition. However, the synthesis was performed only in the racemic series so far. This synthesis was now re-investigated and the catalytic methods for the enantioselective preparation of the chiral key intermediate were evaluated. It was found that Cu-catalyzed allylic substitution of a cinnamyl chloride with MeMgBr in the presence of a Taddol-derived chiral phosphine-phosphite ligand affords the corresponding (1-methylallyl)arene with high enantioselectivity (94% ee ). Hydroboration and subsequent Suzuki coupling gave ( R )-curcuphenol methyl ether from which (–)-α-cedrene was prepared along the route paved by Wender.",10.1055/s-0036-1588602,2016-09-26,0.6723920060911563
Journal of Organic Chemistry,"Catalytic, Asymmetric Synthesis of Siphonarienal","This paper describes the synthesis of the marine natural product, siphonarienal. The key step of this synthesis is an aldol reaction that constructs most of the skeleton and sets all three stereocenters of the target in one step from commercially available starting materials. Deoxygenation and chain homologation steps complete the synthesis.",10.1021/jo0160367,2001-10-03,0.6723370448588709
Journal of Organic Chemistry,Development of an Enantioselective Route toward the <i>Lycopodium</i> Alkaloids: Total Synthesis of Lycopodine,"Synthesis of a C(15)-desmethyl tricycle core of lycopodine has been accomplished. Key steps in the synthetic sequence include organocatalytic, intramolecular Michael addition of a keto sulfone and a tandem 1,3-sulfonyl shift/Mannich cyclization to construct the tricyclic core ring system. Synthetic work toward this natural product family led to the development of N-(p-dodecylphenylsulfonyl)-2-pyrrolidinecarboxamide, an organocatalyst which facilitates enantioselective, intramolecular Michael additions. A detailed mechanistic discussion is provided for both the intramolecular Michael addition and the sulfone rearrangement. Finally, the application of these discoveries to the enantioselective total synthesis of alkaloid lycopodine is described.",10.1021/jo100916x,2010-06-29,0.6723177806846085
Organic Process Research & Development,Development of a Practical Process for the Synthesis of PDE4 Inhibitors,"A practical, safe, and efficient process for the synthesis of PDE4 (phosphodiesterase type 4) inhibitors represented by 1 and 2 was developed and demonstrated on a multi-kilogram scale. Key aspects of the process include the regioselective synthesis of dihydrothieno[3,2- d ]pyrimidine-2,4-diol 9 and the asymmetric sulfur oxidation of intermediate 11 .",10.1021/acs.oprd.6b00104,2016-04-28,0.6723053343096983
Organic Process Research & Development,Some Items of Interest to Process R&amp;D Chemists and Engineers,"An improved synthesis of the potent and highly selective COX-2 inhibitor, GW406381X, is described by Whitehead and co-workers at GlaxoSmithKline (",10.1021/op7000832,2007-05-01,0.6722578700874149
Tetrahedron,A novel one-step efficient method for the synthesis of tetrahydroindoles from 1-(1-pyrrolidino)cyclohexene and chloropyruvates,,10.1016/j.tetlet.2008.05.044,2008-05-14,0.6722494172526168
Journal of the American Chemical Society,A Concise Total Synthesis of (−)-Quinocarcin via Aryne Annulation,"Described in this report is a rapid asymmetric total synthesis of the tetrahydroisoquinoline antitumor antibiotic (-)-quinocarcin. The sequence employs a mild fluoride-induced aryne annulation developed in our laboratories to build a key isoquinoline-containing intermediate comprising the entire carbon scaffold of the natural product. This intermediate is advanced through six additional steps to the target alkaloid, providing the shortest synthetic route to (-)-quinocarcin reported to date.",10.1021/ja808112y,2008-11-26,0.672222637901917
Organic Letters,Total Synthesis of (±)-7-<i>epi</i>-Nemorosone,A concise total synthesis of (±)-7-epi-nemorosone is reported. Our synthetic approach establishes a viable route to polycyclic polyprenylated acylphloroglucinol natural products (PPAP's) bearing a C-7 endo prenyl side chain. Key steps include retro-aldol-vinyl cerium addition to a hydroxy adamantane core scaffold and palladium-mediated deoxygenation.,10.1021/ol300386t,2012-03-26,0.6721491021099362
Angewandte Chemie International Edition,Total Synthesis of Spirastrellolide F Methyl Ester—Part 2: Macrocyclization and Completion of the Synthesis,"Marvel of the sea: A concise and highly convergent total synthesis of the methyl ester of the marine macrolide spirastrellolide F (see picture), which has exquisite antimitotic properties, is reported. In this approach, the northern and the southern hemispheres of this intricate target are stitched together in only two consecutive steps (Suzuki coupling, Yamaguchi lactonization) without any interim protecting-group manipulations.",10.1002/anie.200906122,2009-12-08,0.672123757499348
Organic Process Research & Development,Double Heck Route to a Dibenzoxepine and Convergent Suzuki Cross-Coupling Strategy for the Synthesis of an MR Antagonist,"High Resolution Image Download MS PowerPoint Slide A practical pilot plant convergent synthesis of MR antagonist LY2623091 was established. For synthesis convergence, a vinyl bromide geometric isomer and chiral alaninol derivative were required building blocks. Key to the synthesis route development is a stereoselective synthesis of the E -vinyl bromide via a sequential double Heck reaction, Suzuki–Miyaura cross-coupling of the vinyl bromide, a selective nitro reduction, and a highly sensitive cyanamide hydrolysis to the urea. Improvements in yield and processing were accomplished by two sets of telescoping methods which decreased the manufacturing time and provided purity enhancements.",10.1021/acs.oprd.6b00368,2016-12-19,0.6720758773049068
Journal of the American Chemical Society,Enantioselective Route to Platensimycin:  An Intramolecular Robinson Annulation Approach,"An enantioselective route to the tetracyclic core structure of the novel antibiotic lead compound platensimycin is accomplished in 10 steps from simple commercially available starting materials. Highlights of this synthesis include (1) a regio- and enantioselective Diels−Alder reaction between methyl acrylate and methyl cyclopentadiene to give adduct 2 with essentially complete regio-, diastereo-, and enantiocontrol; (2) oxidative decarboxylation of ester 2 using nitrosobenzene; (3) a one-pot reductive cyanation of lactone 4; (4) a stereoselective intramolecular Michael addition between an α -branched aldehyde moiety and a β -substituted enone part of 8, followed by aldol dehydration in one pot to give the Robinson annulation product 9 .",10.1021/ja073547n,2007-07-14,0.67205370925096
Organic Process Research & Development,Practical Enantioselective Synthesis of a 3-Aryl-3-trifluoromethyl-2-aminopropanol Derivative,"Development of a large-scale enantioselective synthesis of a lead compound containing a 3-aryl-3-trifluoromethyl-2-aminopropanol core is described. A single isomer of 3,3-disubstituted acrylic acid derivative was prepared via Perkin condensation or Horner−Wadsworth−Emmons olefination, followed by hydrolysis. The acid was converted to a chiral acryloxazolidinone derivative. Hydrogenation of the latter on Pd/C in the presence of MgBr 2 proceeded via a chelation-controlled conformation to yield the desired isomer with high selectivity. Subsequent Evans azidation, hydrogenation, reductive cleavage of the chiral auxiliary, and sulfonylation afforded the target compound as a single isomer in high overall yield.",10.1021/op900216v,2009-10-27,0.6720258144609917
Tetrahedron,"A practical route towards α,β-unsaturated δ-lactones based on a [3+3] strategy. Synthesis of (−)-argentilactone",,10.1016/s0040-4039(00)87834-x,1988-01-01,0.6719842611676604
Synthesis,Practical One-Step Synthesis of Koga's Chiral Bases,"A simple, efficient and practical method for the preparation of Koga""s chiral bases is described. The method involves attack of an amine on a styrene oxide-derived aziridinium ion and has allowed the synthesis of novel diamines which cannot be prepared using Koga""s original route.",10.1055/s-2001-12768,2001-01-01,0.6719613037538658
Organic Process Research & Development,Novel and Efficient Synthesis of Potassium-Competitive Acid Blocker Fexuprazan,"Fexuprazan is a novel potassium-competitive acid blocker (P-CAB). The conventional synthesis route involves preparing methyl 5-(2,4-difluorophenyl)-4-methoxy-1 H -pyrrole-3-carboxylate ( 7 ), a key intermediate associated with toxicity concerns, environmental pollution, and low yields. This article aims to develop an innovative synthetic strategy to overcome these limitations. Our approach utilizes 3-aminopropionitrile and methyl 2-(2,4-difluorophenyl)-2-oxoacetate ( 20 ) as key precursors for a streamlined one-pot synthesis of the cyano-containing pyrrole 23, achieving a 90.0% yield. A significant advancement is the subsequent implementation of hydrogen gas as an ecofriendly reductant for direct cyano-to-aldehyde conversion. Starting from cost-effective 1,3-difluorobenzene ( 18 ), the optimized six-step route delivers fexuprazan hydrochloride ( 1 ) with an overall yield of 42.6% at kilogram scale. This improved protocol demonstrates significant advantages in process economics, operational simplicity, and environmental sustainability, establishing a robust platform for industrial-scale manufacture.",10.1021/acs.oprd.5c00255,2025-09-05,0.6719443188826103
Journal of Organic Chemistry,Applications of Sugar Nitrones in Synthesis:  The Total Synthesis of (+)-Polyoxin J<sup>1</sup>,"A convergent synthesis of the peptidyl nucleoside antibiotic (inhibitor of chitin biosynthesis) polyoxin J ( 2 ) by coupling of 5- O -carbamoyl polyoxamic acid ( 3 ) and thymine polyoxin C ( 4 ) is described. These compounds were prepared by chain elongation and amination of sugar-derived aldehydes employing their nitrones as iminium derivatives and the furan ring as a masked carboxyl. Thus, the stereoselective addition of 2-lithiofuran to the l -threose derived N -benzyl nitrone 5 followed by reduction of the resulting hydroxylamine to amine, carbamoylation of the free hydroxy group, and oxidative cleavage of the furan ring to the carboxylate group gave a protected derivative of 3 (30%). The same method was followed for the synthesis of the ribofuranosyl α-amino acid nucleoside 4 (12.6%) starting from the d -ribose derived nitrone 6 . The final coupling was performed by the N -hydroxysuccinimide active ester method in DMSO with the Hünig base (i-Pr 2 EtNH) using a derivative of 3 and unprotected 4 .",10.1021/jo9702913,1997-08-01,0.6718844415978136
Organic Process Research & Development,"Improvements to Enable the Large Scale Synthesis of 1-{[(2S,3S,4S)-3-Ethyl-4-fluoro-5-oxopyrrolidin-2-yl]methoxy}-7-methoxyisoquinoline-6-carboxamide (PF-06650833)","An improved process for the large scale synthesis of 1-{[(2S,3S,4S)-3-ethyl-4-fluoro-5-oxopyrrolidin-2-yl]methoxy}-7-methoxyisoquinoline-6-carboxamide ( 1 ), a candidate currently in clinical development, was developed. Key objectives were to eliminate chromatographic purifications, to maximize the reproducibility of each step, and to improve the yield and efficiency of each step relative to the previous discovery syntheses of 1 . This work was focused on improvements to the synthesis of the stereochemically complex lactam 2 . Steps of particular concern were the preparation of the unsaturated lactam 6, the cuprate conjugate addition reaction to produce 7, and the conversion of 7 to 8 with a high degree of diastereoselection. The solutions to these challenges have permitted the synthesis of 2 in excess of 100 kg, which in turn has permitted 1 to be prepared in sufficient amounts to support further development.",10.1021/acs.oprd.8b00386,2018-11-27,0.6718414328012412
Chemical Science,Synthesis of spongistatin 2 employing a new route to the EF fragment,"An improved route to the EF fragment of the spongistatins has been developed and employed in a synthesis of spongistatin 2. The C48–C51 diene side chain, which lacks the chlorine substituent present in spongistatin 1, presented some compatibility issues during target assembly. These were overcome by implementing a late stage Stille cross coupling to construct the diene portion of the natural product.",10.1039/c3sc50304f,2013-01-01,0.6718396009955069
Angewandte Chemie International Edition,Highly Efficient Total Synthesis of (+)‐Citreoviral,"Only eight steps were required for the total synthesis of (+)-citreoviral (3) from chiral imide 1 in 18 % overall yield. The key steps included a highly anti-selective aldol reaction, the stereoselective iodolactonization of a γ,δ-unsaturated β-hydroxyimide, and an intramolecular SN2 reaction of a tertiary alcohol to form intermediate 2.",10.1002/anie.200454212,2004-06-09,0.6718372166334294
Organic Letters,Tubulysin Synthesis Featuring Stereoselective Catalysis and Highly Convergent Multicomponent Assembly,) has been accomplished in 18 steps in an overall yield of up to 30%. Our work highlights the complexity-augmenting and route-shortening power of diastereoselective multicomponent reaction (MCR) as well as the role of bulky ligands to perfectly control both the regioselective and diastereoselective synthesis of tubuphenylalanine in just two steps. The total synthesis not only provides an operationally simple and step economy but will also stimulate major advances in the development of new tubulysin analogues.,10.1021/acs.orglett.0c01718,2020-06-25,0.6718273594288449
Journal of Organic Chemistry,Total Synthesis of (<i>S</i>)-(+)-Tylophorine Via Enantioselective Intramolecular Alkene Carboamination,"The enantioselective synthesis of (S)-(+)-tylophorine, a potent cancer cell growth inhibitor, has been accomplished in eight steps from commercially available 3,4-dimethoxybenzyl alcohol. A copper (II)-catalyzed enantioselective intramolecular alkene carboamination was employed as the key step to construct the chiral indolizidine ring.",10.1021/jo801024h,2008-06-28,0.6718174304434356
Journal of Organic Chemistry,Synthesis of Antifungal Glucan Synthase Inhibitors from Enfumafungin,"An efficient, new, and scalable semisynthesis of glucan synthase inhibitors 1 and 2 from the fermentation product enfumafungin 3 is described. The highlights of the synthesis include a high-yielding ether bond-forming reaction between a bulky sulfamidate 17 and alcohol 4 and a remarkably chemoselective, improved palladium(II)-mediated Corey-Yu allylic oxidation at the highly congested C-12 position of the enfumafungin core. Multi-hundred gram quantities of the target drug candidates 1 and 2 were prepared, in 12 linear steps with 25% isolated yield and 13 linear steps with 22% isolated yield, respectively.",10.1021/jo300046v,2012-03-16,0.6717923376646064
Synthesis,"Synthesis of 2′- and 3′-Acetoxyolivetols [5-(2- and 3-Acetoxypentyl)-1,3-benzenediols]: Key Intermediates in the Synthesis of Tetrahydrocannabinol Derivatives",,10.1055/s-1980-29193,1980-01-01,0.6717895424190338
Journal of the American Chemical Society,Enantioselective Total Synthesis of (−)-Artatrovirenol A,"We report herein an enantioselective total synthesis of (−)-artatrovirenol A, a structurally unprecedented cage-like sesquiterpenoid. The synthesis features the following key steps: (a) cationic chiral oxazaborolidinium-catalyzed Diels–Alder reaction between isoprene and ethyl ( E )-5-(( tert -butyldimethylsilyl)oxy)-4-oxopent-2-enoate for the rapid synthesis of an enantioenriched 10-carbon bicyclic lactone; (b) union of two enantioenriched fragments by a diastereoselective Mukaiyama–Michael addition for the convergent assembly of an intermediate with all 15 carbons of the natural product; (c) intramolecular de Mayo [2 + 2] cycloaddition/retro-aldol sequence transforming a bicyclic compound to a tetracyclic one with concomitant generation of a five- and a seven-membered ring; (d) Lewis acid-triggered intramolecular ring opening of epoxide generating the norbornane substructure; and (e) Chugaev elimination converting the norbornane to the more strained norbornene.",10.1021/jacs.3c09683,2023-10-24,0.6717596652480597
Organic Letters,Enantioselective Syntheses of FR901464 and Spliceostatin A: Potent Inhibitors of Spliceosome,"Enantioselective syntheses of FR901464 and spliceostatin A, potent spliceosome inhibitors, are described. The synthesis of FR901464 has been accomplished in a convergent manner in 10 linear steps (20 total steps). The A-tetrahydropyran ring was constructed from (R)-isopropylidene glyceraldehyde. The functionalized tetrahydropyran B-ring was synthesized utilizing a Corey-Bakshi-Shibata reduction, an Achmatowicz reaction, and a stereoselective Michael addition as the key steps. Coupling of A- and B-ring fragments was accomplished via cross-metathesis.",10.1021/ol4024634,2013-09-19,0.6717256772153175
Journal of Organic Chemistry,Synthesis of the Aminocyclitol Units of (−)-Hygromycin A and Methoxyhygromycin from <i>myo</i>-Inositol,"Concise and efficient syntheses of the aminocyclitol cores of hygromycin A (HMA) and methoxyhygromycin (MHM) have been achieved starting from readily available myo-inositol. Reductive cleavage of myo-inositol orthoformate to the corresponding 1,3-acetal, stereospecific introduction of the amino group via the azide, and resolution of a racemic cyclitol derivative as its diastereomeric mandelate esters are the key steps in the synthesis. Synthesis of the aminocyclitol core of hygromycin A involved chromatography in half of the total number of steps, and the aminocyclitol core of methoxyhygromycin involved only one chromatography.",10.1021/jo300444b,2012-06-05,0.6717238550861453
Journal of the American Chemical Society,Total Synthesis of (±)-Cortistatin J from Furan,"A concise, diastereoselective total synthesis of (±)-cortistatin J has been completed in 20 steps from furan. Key steps include an intramolecular [4 + 3] cyclization of a disubstituted furan with a (Z)-2-(trialkylsilyloxy)-2-enal to construct the tetracyclic core and a (Z)-vinylsilane/iminium ion cyclization to form the A ring.",10.1021/ja206138d,2011-07-16,0.6717115837658234
Journal of Organic Chemistry,"Diastereoselective Amidoalkylation of (3<i>S</i>,7a<i>R</i>)-6-Benzyl-7-hydroxy-3-phenyltetra- hydro-5<i>H</i>-imidazo[1,5-<i>c</i>][1,3]thiazol-5-one :  A Short and Highly Efficient Synthesis of (+)-Biotin",A short and highly efficient synthesis of (+)-biotin in 10 steps with 20% overall yield has been achieved from L-cysteine involving amidoalkylation of hydroxy imidazothiazolone 4 via an acyliminium ion intermediate to furnish C-7-substituted imidazothiazolones 5b as the key step.,10.1021/jo0488107,2005-01-27,0.671711396795879
Tetrahedron,"A new route to 3,4-disubstituted piperidines: formal synthesis of (−)-paroxetine and (+)-femoxetine",,10.1016/j.tetlet.2005.10.049,2005-11-03,0.6716925284284966
Tetrahedron,"Synthesis of CJ-15,208, a novel κ-opioid receptor antagonist",,10.1016/j.tetlet.2010.07.086,2010-07-22,0.6716430607598286
Organic Process Research & Development,"An Efficient and Telescopic Process for Valsartan, an Angiotensin II Receptor Blocker","An efficient, telescopic, and scalable process for an antihypertensive drug substance, valsartan with an overall yield of 58%, and ∼99.9% purity is described. A simple, and safe process is developed for the recovery of tributyltin chloride from the tributyltin hydroxide, byproduct formed in the tetrazole ring construction, and reused in the synthesis of valsartan.",10.1021/op3000306,2012-03-05,0.6716239856846247
Angewandte Chemie International Edition,Total Synthesis of (−)‐atrop‐Abyssomicin C,"Rolling in the deep: An enantioselective synthesis of a marine antibiotic (−)-atrop-abyssomicin C (see scheme) is described. The key steps of the synthetic sequence are the application of dual catalysis in the formation of the cyclohexane core, the gold-catalyzed formation of a tricyclic spirotetronate unit, and a highly efficient eleven-membered ring closure by a Nozaki–Hiyama–Kishi reaction.",10.1002/anie.201108223,2012-04-23,0.6715891432291736
Journal of the American Chemical Society,"Total Synthesis of Bleomycin Group Antibiotics. Total Syntheses of Bleomycin Demethyl A<sub>2</sub>, Bleomycin A<sub>2</sub>, and Decarbamoyl Bleomycin Demethyl A<sub>2</sub>","The total syntheses of bleomycin A 2 ( 1 ) by two routes are described. The final step in the synthesis of bleomycin A 2 involves methylation of bleomycin demethyl A 2 ( 2 ). This bleomycin derivative is of interest mechanistically, and can also provide access to other bleomycins via its known chemical conversion to bleomycinic acid. Accordingly, the synthetic strategy presented represents a particularly versatile approach for the elaboration of a wide variety of BLM congeners. Bleomycin was constructed from five key intermediates, the syntheses of which are described. 1,6-Di- O -acetyl-3,4-di- O -benzyl-2- O -[2,4,6-tri- O -acetyl-3- O- ( N -acetylcarbamoyl)-α- d -mannopyranosyl]-β- l -gulopyranose ( 3 ) was converted quantitatively to its disaccharide chloride ( 4 ), the latter of which was condensed with N α, N im -bis( t -Boc)-( S )- erythro -β-hydroxyhistidine ( 7 ) to provide α- O -glycosidated product 16 . The subsequent couplings with benzyl valerate 8, threonylbithiazole 9, and N α -t- Boc-pyrimidoblamic acid ( 10 ) afforded access to bleomycin demethyl A 2 ( 2 ) and decarbamoyl bleomycin demethyl A 2 ( 26 ). Although it was obtained as a byproduct of the synthesis of BLM, the synthesis of decarbamoyl bleomycin demethyl A 2 nonetheless constitutes the first report of synthetic access to this BLM congener that is of particular importance from a mechanistic perspective. This BLM can be used to resolve the issue of the participation of the carbamoyl group as a metal ligand in metallobleomycins. Also reported is a new route to bleomycin demethyl A 2 that employed an unprotected carbamoyl group throughout the synthesis. In conjunction with the use of the uncharged methylthiopropylamide C-substituent, the latter strategy permitted improved functional group manipulation and thereby afforded intermediates that could be purified with greater facility. Because the synthesis of bleomycin is limited by the efficiency of elaboration of the carbohydrate moiety, a study was carried out to define improved methods for the preparation of this constituent of BLM. Three new routes were explored, and a route involving the intermediacy of disaccharide activated as a glycosyl bromide was found to be particularly efficient and convenient. Also of importance was the finding that activation of carbohydrate intermediates as their glycosyl trichloroacetimidates permitted the requisite couplings to be carried out conveniently and in good yields. Synthetic BLM demethyl A 2 was shown to have the same potency as a naturally derived sample in a plasmid DNA relaxation assay. The sequence selectivity of DNA cleavage by synthetic and authentic Fe(II)·BLMs was also shown to be the same. Also established for the first time for any synthetic bleomycin was the actual chemistry of DNA degradation, which is the same as that for naturally derived bleomycins.",10.1021/ja9819458,1998-10-22,0.6715747558228627
European Journal of Organic Chemistry,Total Synthesis of Bulgarein,"Abstract Here we report an efficient and short total synthesis of bulgarein ( 1 ), a natural compound from Bulgaria inquinans with cytotoxic activity. Key steps in the total synthesis are a Suzuki‐Miyaura coupling reaction of two substituted naphthalene derivates followed by a polyphosphoric acid (PPA) mediated condensation reaction to form the benzo[ j ]fluoranthene skeleton. Bulgarein ( 1 ) was achieved over 4 steps with an overall yield of 25 %.",10.1002/ejoc.202101576,2022-04-05,0.67156693804256
Organic Process Research & Development,"Pilot Scale Process Development of SL65.0102-10, an<i>N</i>-Diazabicyclo[2.2.2]-octylmethyl Benzamide","The process development and improvements for route selection, adapted to large scale for the pilot-scale preparation of SL65.0102-10, an N -diazabicyclo[2.2.2]-octylmethyl benzamide, a 5-HT 3 and 5-HT 4 receptor active ligand for the treatment of neurological disorders such as cognition impairment, are described in this article. Notable steps and enhancements are compared to the original route, including the improvement of a chiral epoxide synthesis by shortening the number of chemical steps, the deprotection of a quaternary ammonium salt, and the redesign of the final amidification coupling to avoid chromatography.",10.1021/acs.oprd.6b00262,2016-12-14,0.6715462233028695
Organic Letters,Total Synthesis of (+)-Crocacin C,"The first asymmetric synthesis of (+)-crocacin C (3) is described which served to confirm the absolute configuration of this compound. The key step in the sequence was the stereoselective assembly of the (E,E)-diene amide side chain by a Stille cross-coupling between the stannane 5 and vinyl iodide 6.",10.1021/ol0064664,2000-09-23,0.6715302611567011
Synlett,"A Synthesis of (S)-(-)-Umbelactone and Related α,β-Butenolides","The development of an asymmetric route for the synthesis of α,β-butenolide building blocks, starting from commercially available d-mannitol, is described. The devised route was applied to a synthesis of the (S)-(-)-enantiomer of the antiviral natural product umbelactone, together with the construction of other synthetically useful lactone structures.",10.1055/s-0029-1219181,2010-01-15,0.6714974805495988
Organic Process Research & Development,Synthesis of the CETP Inhibitor Torcetrapib:  The Resolution Route and Origin of Stereoselectivity in the Iminium Ion Cyclization,"A practical, efficient synthesis of (−)-(2 R,4 S )-4-[(3,5-bis-trifluoromethyl-benzyl)methoxycarbonylamino]-2-ethyl-6-trifluoromethyl-3,4-dihydro-2H-quinoline-1-carboxylic acid ethyl ester ( 1 ), a cholesteryl ester transfer protein (CETP) inhibitor, is described. The key reaction in the synthesis, addition of an N -vinylcarbamate to an iminium ion rapidly followed by an iminium ion cyclization onto the aryl ring, sets up the cis relationship of the two subsituents of the tetrahydoquinoline ring of 6 . The origin of the high cis stereoselectivity in the cyclization was explored using high-level quantum chemistry calculations.",10.1021/op060014a,2006-03-16,0.6714724716740464
Journal of Organic Chemistry,Aziridine−Allylsilane-Mediated Total Synthesis of (−)-Yohimbane,"A total asymmetric synthesis of (-)-yohimbane and ent-alloyohimbane is reported. The synthesis utilizes a novel aziridine-allylsilane cyclization reaction as a key step in the synthesis. Treatment of optically pure aziridine-allylsilane 16 with BF(3).OEt(2) provided a mixture of aminomethyl substituted carbocycles trans-20a and cis-20b in excellent yield and modest diastereoselectivity (trans/cis 3:1). Alkylation of the tosylamide followed by oxidation of the olefin in 20 provided the lactam 38, which was converted to (-)-yohimbane and ent-alloyohimbane by a Bischler-Napieralski reaction. The synthesis provided (-)-yohimbane in eight steps and 24% overall yield (from 16).",10.1021/jo9825097,1999-04-01,0.6714222246332399
Journal of the American Chemical Society,Convergent and Biomimetic Enantioselective Total Synthesis of (−)-Communesin F,"The first biomimetic enantioselective total synthesis of (-)-communesin F based on a late-stage heterodimerization and aminal exchange is described. Our synthesis features the expedient diazene-directed assembly of two advanced fragments to secure the congested C3a-C3a' linkage in three steps, followed by a highly efficient biogenetically inspired aminal reorganization to access the heptacyclic communesin core in only two additional steps. Enantioselective syntheses of the two fragments were developed, with highlights including the catalytic asymmetric halocyclization and diastereoselective oxyamination reactions of tryptamine derivatives, a stereoselective sulfinimine allylation, and an efficient cyclotryptamine-C3a-sulfamate synthesis by either a new silver-promoted nucleophilic amination or a rhodium-catalyzed C-H amination protocol. The versatile syntheses of the fragments, their stereocontrolled assembly, and the efficient aminal exchange as supported by in situ monitoring experiments, in addition to the final stage N1'-acylation of the communesin core, provide a highly convergent synthesis of (-)-communesin F.",10.1021/jacs.6b04072,2016-05-31,0.6713842110101399
Tetrahedron,"Novel route to spiropiperidines using N-methyl-4-piperidone, malononitrile and electrophiles",,10.1016/j.tetlet.2011.12.129,2012-01-10,0.6713472628996977
Angewandte Chemie International Edition,A Highly Step‐Economical Synthesis of Dictyostatin,"Less is more: An efficient synthesis of the anti-mitotic macrolide dictyostatin proceeds with a longest linear sequence of 14 steps, and allows the rapid production of multi-gram quantities of each of the three fragments from which the natural product is assembled in just four or five steps. The key step is a scalable one-step synthesis of the C(12)–C(14) and C(20)–C(22) stereotriads.",10.1002/anie.201302565,2013-05-10,0.6713238924143584
Journal of Organic Chemistry,Total Synthesis of (+)-Schweinfurthins B and E,"The first total synthesis of (+)-schweinfurthin B, a potent and differentially active cytotoxic agent, has been accomplished. Completion of the synthesis required just 16 steps in the longest linear sequence from commercially available vanillin. Key synthetic transformations included a Shi epoxidation and an efficient cascade cyclization initiated by treatment of the resulting epoxide with BF(3).OEt(2). Furthermore, use of a methyl ether as a stable protecting group for benzylic alcohols dramatically increased the efficiency of the overall sequence. The benzylic ether can be removed from this electron-rich aromatic system through oxidation with DDQ that provided the desired aldehyde intermediate in quantitative yield and shortened the synthetic sequence. Introduction of the A-ring diol in the required cis stereochemistry then became viable through a short sequence highlighted by an aldol condensation with benzaldehyde to introduce an olefin as a latent carbonyl group at the C-3 position. This synthesis established for the first time the absolute stereochemistry of the natural product, and provides access to material on a scale that will advance biological studies. The total synthesis of the closely related compound (+)-schweinfurthin E also is reported.",10.1021/jo901161m,2009-08-21,0.6712970896335965
Journal of Organic Chemistry,Asymmetric Total Synthesis of (+)-Cannabisativine,"The asymmetric total synthesis of natural (+)-cannabisativine 1 was completed in 19 steps and 7% overall yield. The key synthetic intermediate 29 was prepared with a high degree of stereocontrol in 12 steps starting from chiral 1-acylpyridinium salt 10. Addition of zinc enolate 11 to pyridinium salt 10 furnished dihydropyridone 12 containing two contiguous stereocenters of the correct absolute configuration. Luche reduction of ketone 16 afforded diol 17 in high yield (96%) and excellent diastereoselectivity. The Mukaiyama-Michael reaction of pyridones 27a/b with O-silyl ketene acetal 32 gave phenyl selenyl ketones 33a/b with complete stereoselectivity. Elimination of cis-beta-hydroxyselenides 34 and 35 effected the regiocontrolled preparation of tetrahydropyridine derivative 29. Several approaches to the macrocyclic ring closure of the 13-membered ring were investigated, ultimately leading to the completion of an asymmetric synthesis of the target compound with a high degree of stereocontrol.",10.1021/jo049724+,2004-04-29,0.6712705921057599
Organic Process Research & Development,Development of an Improved Process To Prepare a Key Intermediate in the Manufacture of Sotorasib,"Sotorasib is a first-in-class KRAS G12C inhibitor with a unique carbon–nitrogen atropisomer. Described herein is the development of an improved second-generation process to manufacture a key sotorasib intermediate, rac- 4 . Notable improvements to the second-generation process include the development of a three-step fully telescoped sequence in acetonitrile and the use of phosgene as an isocyanating agent, which allowed for dichloromethane, aqueous extractive work-ups, and distillations to be completely removed from the process. Compared to the first-generation process, these process improvements led to a 97% reduction in organic solvent usage and a 71% reduction in wastewater generation and still maintains a 75% yield and >99.5% purity of rac - 4 in the overall process.",10.1021/acs.oprd.5c00043,2025-06-02,0.6712668602301334
Journal of the American Chemical Society,A Convergent Approach to Phragmalin-Type Limonoids: Total Synthesis of Thaigranatin P,"Herein, we report the total synthesis of erythrocarpines M and L and thaigranatin P, topologically complex phragmalin-type limonoids, the latter exhibiting potent agonism on the human pregnane X receptor (hPXR). A key transformation is a SmI 2 -mediated reductive coupling of an aldehyde and an alkene, which constructs the signature tricyclo[3.3.1 2,10 .1 1,4 ]decane framework characteristic of phragmalin natural products. The synthesis features a strategically convergent construction of the phragmalin core structure via a cuprate addition, triflation, and intramolecular Heck reaction sequence. This route offers a versatile platform for the synthesis of structurally diverse phragmalin analogs for future biological investigation.",10.1021/jacs.5c13081,2025-09-26,0.6712660651688803
Organic Process Research & Development,A Practical Synthesis of a Chiral Analogue of FTY720,A practical synthesis of 1 involving a catalytic enantioselective construction of the quaternary carbon from imine 10 (derived from 13 and 14 ) and alkyl iodide 5 using Maruoka’s chiral catalyst 11 is described. This asymmetric alkylation followed by hydrolysis to amino acid 9 was accomplished in good yield with high chemical purity (>98%) and chiral purity (>96% ee). The improved synthesis enabled production of 1 in seven chemical steps (six isolations) in an overall yield of 22%.,10.1021/op800144h,2008-09-26,0.6712584766707873
Organic Letters,Total Synthesis of (−)-8-Deoxyserratinine via an Efficient Helquist Annulation and Double N-Alkylation Reaction,"The first enantioselective total synthesis of (-)-8-deoxyserratinine has been achieved in 15 steps from enone 4 with 7% overall yield. The key features include a highly efficient Helquist annulation to furnish the cis-fused 6/5 bicycle, facile construction of the aza nine-membered ring system employing double N-alkylation strategy, as well as asymmetric Shi epoxidation, delivering the desired beta-epoxide stereospecifically.",10.1021/ol1012444,2010-06-29,0.6712446018955874
Synlett,"A Facile Approach to the Synthesis of 3-(6-Chloro-thiazolo[5,4-b]pyridin-2-ylmethoxy)-2,6-difluoro-benzamide (PC190723)","Practical synthesis of PC 190723, a bacterial cell division protein Ftsz inhibitor, has been achieved in a high overall yield of 45% in six steps from commercially available starting materials.",10.1055/s-0031-1290777,2012-04-01,0.6712314352207823
Organic Letters,"Total Synthesis of an Oxepine Natural Product, (±)-Janoxepin","The total synthesis of (±)-janoxepin, a novel antiplasmodial d-leucine derived oxepine-pyrimidinone-ketopiperazine isolated from the fungus Aspergillus janus, is described. The cornerstones of the synthetic route are pyrimidinone preparation, ring-closing metathesis, aldol introduction of the enamide, and dihydro-oxepine elaboration. This synthetic route proved very efficient for the formation of a number of janoxepin analogues, including dihydro-janoxepin and tetrahydro-janoxepin.",10.1021/ol300039x,2012-01-30,0.6711828315936871
Organic Letters,Approach to the Synthesis of Antitumor Quassinoids from Labdane Diterpenes:  An Efficient Synthesis of a Picrasane-Related Intermediate,"[structure: see text]. The tetracyclic ketal 24, a suitable intermediate for the synthesis of antitumor pentacyclic quassinoids, has been efficiently prepared from communic acids (5a-c), via methyl ketone 9. The synthetic sequence from 9 to 24 consists of 15 steps in 12% overall yield.",10.1021/ol0065322,2001-02-07,0.6711654114503057
Journal of Organic Chemistry,Total Synthesis of Bafilomycin V<sub>1</sub>:  A Methanolysis Product of the Macrolide Bafilomycin C<sub>2</sub>,"A synthesis of bafilomycin V(1), a methanolysis product of the macrolide natural product bafilomycin C(2), is described. The route utilizes chiral nonracemic allenylzinc reagents, prepared in situ from propargylic mesylates, to access key segments of this methyl ester. The acetylenic moieties of the derived homopropargylic alcohol adducts play an important role in further elaboration of these subunits. Final assemblage of the 25-carbon chain, containing 12 stereocenters, an alpha-methoxy Z,E 1,3-dienic ester, and an additional E,E 1,3-diene, was achieved through Stille coupling of an acetylene-derived vinyl stannane and vinyl iodide of approximate equal complexity. Attempted cyclization of several C15 hydroxy acid derivatives to the 16-membered lactone bafilomycin A(1), a potent inhibitor of vacuolar ATPases, could not be achieved.",10.1021/jo015864x,2002-01-04,0.6711200925890392
Tetrahedron,A new route to novel 10-deoxoartemisinins,,10.1016/j.tetlet.2005.04.042,2005-05-06,0.6711122072863609
European Journal of Organic Chemistry,Unified Total Synthesis of Hetiamacins A–D,"A concise enantioselective total synthesis of hetiamacin A has been accomplished from a known l ‐aspartic acid derivative by an eight‐step sequence that features ammonolytic opening of the γ‐lactone moiety of amicoumacin C followed by 1,3‐oxazinane ring formation in one pot. Hetiamacins B–D with putatively assigned stereochemistries have also been synthesized from amicoumacin C, each in three steps involving tetrahydro‐4(1 H )‐pyrimidinone ring formation. The excellent NMR spectroscopic agreement of the synthetic materials with the corresponding natural products, coupled with biosynthetic considerations, has enabled the full stereochemical assignments of hetiamacins B–D.",10.1002/ejoc.201901114,2019-08-16,0.6711101070930335
Tetrahedron,"Efficient synthesis of sitagliptin phosphate, a novel DPP-IV inhibitor, via a chiral aziridine intermediate",,10.1016/j.tetlet.2013.09.136,2013-10-03,0.6710388750535164
Tetrahedron,"An efficient asymmetric catalytic hydrogenation of 4-aryl coumarins, preparation of a key intermediate in the synthesis of a class of endothelin receptor antagonists",,10.1016/s0040-4039(99)00478-5,1999-04-01,0.6709806254696334
Synthesis,Enantioselective Synthesis of the 3C-Protease Inhibitor (-)-Thysanone by a Staunton-Weinreb Annulation Strategy,"The total synthesis of (-)-thysanone is described. The key step involves the addition of an o-toluate anion to a lactone to create the naphthopyran framework (Staunton-Weinreb annulation). This synthesis further confirms the absolute stereochemistry of the natural product to be 1R,3S. © Georg Thieme Verlag Stuttgart.",10.1055/s-0029-1217390,2009-06-08,0.670908001129247
Organic Letters,"3,8-Diazabicyclo[3.2.1]octan-2-one Peptide Mimetics:  Synthesis of a Conformationally Restricted Inhibitor of Farnesyltransferase","A new synthesis of the 3,8-diazabicyclo[3.2.1]octan-2-one framework is described. Transannular enolate alkylation of piperazinone derivatives provides a flexible route to highly constrained bicyclic peptidomimetic synthons with substitution at the Calpha position. The chemistry was used to produce a conformationally constrained farnesyltransferase inhibitor, which aided the elucidation of enzyme-bound conformation.",10.1021/ol015504w,2001-02-17,0.6708864137579946
Organic Letters,This Paper Has Been Withdrawn.Highly Convergent Route to Cyclopeptide Alkaloids. Total Synthesis of Ziziphine N,,10.1021/ol062639z,2006-11-23,0.6708816540690923
Organic Letters,"Total Synthesis of L-156,373 and an oxoPiz Analogue via a Submonomer Approach","The first chemical synthesis of L-156,373 (1), a potent oxytocin receptor antagonist isolated from Streptomyces silvensis, is reported. Assembly of the unusual d-Piz-l-Piz dipeptide subunit was achieved through a sequential electrophilic amination-acylation-deprotection strategy followed by late-stage Piz ring formation. Synthesis and incorporation of a novel N-hydroxy-l-isoleucine building block is also described. This submonomer approach was further applied to the expedient synthesis of a di-δ-oxopiperazic acid analogue of 1 starting from Fmoc-Glu( tBu)-OH building blocks.",10.1021/acs.orglett.8b00912,2018-04-18,0.6708726193650525
Tetrahedron,"Efficient synthesis of isogranulatimide C, an analogue of the marine G2 checkpoint inhibitor alkaloid isogranulatimide",,10.1016/j.tetlet.2011.09.109,2011-10-02,0.6708257752714993
Angewandte Chemie International Edition,Concise Total Synthesis of Cruentaren A,"Converging on the target: The highly cytotoxic F-ATPase inhibitor cruentaren A constitutes an interesting lead in the quest for innovative chemotherapeutic agents for the treatment of various diseases, including cancer. Its synthesis was achieved in an overall yield of 3 % by an expeditious convergent route involving a ring-closing alkyne metathesis reaction (RCAM) for the formation of the macrocyclic ring (see picture).",10.1002/anie.200703839,2007-10-31,0.6708164161625082
Journal of Organic Chemistry,"Asymmetric Synthesis of Merck’s Potent hNK<sub>1</sub> Antagonist and Its Stereoisomers via Tandem Acylation/[3,3]-Rearrangement of 1,2-Oxazine <i>N</i>-Oxides","An asymmetric total synthesis of Merck’s hNK 1 antagonist and three of its stereoisomers was accomplished in 10 steps. The synthesis involves a stereoselective assembly of 1,2-oxazine N -oxide by the [4 + 2]-cycloaddition, site-selective C–H oxygenation using a novel tandem acylation/[3,3]-rearrangement process and the reductive 1,2-oxazine ring contraction into a pyrrolidine ring as key stages. Using this strategy, the fused pyrrolidine subunit was constructed with exceptionally high regio- and stereoselectivities. The approach described here can be used to access enantiopure 3,4-disubstituted prolinols, which are frequently found in pharmaceutically relevant molecules and organocatalysts.",10.1021/acs.joc.0c01322,2020-08-11,0.6708037478164492
Angewandte Chemie International Edition,Total Synthesis of (−)‐Nakadomarin A,"A highly efficient 12-step synthesis of the marine alkaloid (-)-nakadomarin A has been accomplished. The key advanced intermediate, a tetracyclic ketone derivative, was constructed in just seven steps using a sequence that includes an asymmetric Pauson-Khand reaction, an Overman rearrangement reaction, a ring-closing metathesis reaction, and an amination reaction. Late introduction of the furan ring during the synthesis of (-)-nakadomarin A means that the key tetracyclic ketone derivative has the potential to serve as an advanced intermediate for the synthesis of related marine alkaloids.",10.1002/anie.201600990,2016-02-29,0.6707815348583868
European Journal of Organic Chemistry,"Synthesis of the Sesquiterpenes Albicanol, Drimanol, and Drimanic Acid, and the Marine Sesquiterpene Hydroquinone Deoxyspongiaquinol","Abstract A Ti III ‐mediated radical cyclization cascade has been used for the synthesis of the sesquiterpenes (+)‐albicanol, (+)‐drimanol, and (+)‐drimanic acid. Starting from all ‐ trans ‐farnesol, (+)‐albicanol could be prepared in seven steps in an overall yield of 14.9 %. Furthermore, a highly diastereoselective hydrogenation of (+)‐albicanol to give (+)‐drimanol has been developed. We used the synthesized (+)‐drimanic acid to achieve the first synthesis of the marine sesquiterpene hydroquinone deoxyspongiaquinol and the quinone deoxyspongiaquinone. Thus, this synthetic strategy gave access to five natural products.",10.1002/ejoc.201402873,2014-09-18,0.6707748180751658
Synlett,Improved Synthesis of a New Nonpeptidic Inhibitor of Human Neutrophil Elastase,"All articles of this category A practical method for the synthesis of ONO-6818 {2-(5-Amino-6-oxo-2-phenylhydropyrimidinyl)- N -[2-(5- tert -butyl-1,3,4-oxadiazol-2-yl)-1-(methylethyl)-2-oxoethyl]acetamide} ( 1 ), the first clinical candidate for a nonpeptidic orally active inhibitor of human neutrophil elastase (HNE), was developed. This method includes a Lossen rearrangement instead of an explosive Curtius rearrangement and the improved preparation of the α-aminoketone. enzyme inhibitor - aminopyrimidinone - ketooxadiazole - Lossen rearrangement - anionic addition reaction",10.1055/s-2001-10786,2001-12-31,0.6707409069563979
Synthesis,The Stereoselective Total Synthesis of Aculeatin A and B via Prins Cyclization,The total synthesis of aculeatins A and B is described proving the versatility of Prins cyclization in natural product synthesis. The approach is convergent and highly stereoselective. Morpholine amide coupling with an alkyne and PIFA-mediated oxidative spirocyclization were utilized as key steps.,10.1055/s-0029-1217144,2009-11-27,0.670725014248338
Journal of Organic Chemistry,Total Syntheses of Epothilones B and D,"A convergent, total synthesis of epothilones B (2) and D (4) is described. The key steps are Normant coupling to establish the desired (Z)-stereochemistry at C12-C13, Wadsworth-Emmons olefination of methyl ketone 28 with the phosphonate ester 8, diastereoselective aldol condensation of aldehyde 5 with the enolate of keto acid derivatives to form the C6-C7 bond, selective deprotection of acid 52, and macrolactonization.",10.1021/jo048742o,2004-11-18,0.6707219773181852
Organic Letters,"Scalable and Divergent Total Synthesis of (+)-Colletoic Acid, a Selective 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitor","An efficient and divergent total synthesis of (+)-colletoic acid, a selective 11-β hydroxysteroid dehydrogenase 1 (11-βHSD1) inhibitor, is presented along with its biological activity at the whole-cell level. A scalable, asymmetric synthetic strategy was designed featuring a diversity-oriented synthesis utilizing a diastereoselective intramolecular 5-exo-Heck reaction as the key step to provide the quaternary spirocenter intermediate 9 in multigram scale, thus establishing a platform for further structure-activity relationship studies and providing access to other acorane family members.",10.1021/ol402842u,2013-11-01,0.6707122582674221
Organic Letters,Total Synthesis of (−)-Irijimaside A Enabled by Ni/Zr-Mediated Reductive Ketone Coupling,"The total synthesis of marine macrolide glycoside (-)-irijimaside A is described. Key to the synthesis is the convergent fragment assembly enabled by nickel/zirconocene-mediated one-pot reductive ketone coupling. At the last stage of the synthesis, Stille coupling and glycosylation led to the first total synthesis of (-)-irijimaside A.",10.1021/acs.orglett.4c01367,2024-05-15,0.6706969282062508
Tetrahedron,An efficient route to disymmetrically substituted calix[6]arenes. Synthesis of novel ligands presenting a N 2 S or N 3 CO 2 − binding core,,10.1016/j.tetlet.2004.04.103,2004-05-11,0.670654124703231
Tetrahedron,An efficient route to disymmetrically substituted calix669arenes. Synthesis of novel ligands presenting a N2S or N3CO2$minus; binding core,,10.1016/s0040-4039(04)00894-9,2004-05-26,0.670654124703231
Organic Letters,Asymmetric Synthesis of Lysergic Acid via an Intramolecular (3+2) Dipolar Cycloaddition/Ring-Expansion Sequence,"An effective, potentially scalable asymmetric synthesis of lysergic acid, a core component of the ergot alkaloid family, is reported. The synthesis features the strategic combination of an intramolecular azomethine ylide cycloaddition and Cossy-Charette ring expansion to assemble the target's C- and D-rings. Simple functional group manipulation produced a compound that had been converted to lysergic acid in four steps, thus constituting a formal synthesis of the natural product. The strategy may be used to prepare novel ergot analogues that include unnatural antipodes and may be more amenable to analogue generation relative to prior approaches.",10.1021/acs.orglett.1c02337,2021-08-12,0.6706503439527008
Synthesis,"A New Synthesis of 4,5-Unsubstituted 1,3-Dioxoles","All articles of this category A synthesis of 4.5-unsubstituted 1,3-dioxoles in two steps from easily accessible 1,3-dioxolanes is described.",10.1055/s-1987-27991,1987-01-01,0.6706446174575592
Organic Letters,De Novo Synthesis of a <scp>d</scp>-Galacturonic Acid Thioglycoside as Key to the Total Synthesis of a Glycosphingolipid from <i>Sphingomonas </i><i>yanoikuyae</i>,"A concise synthesis of a differentially protected D-galacturonic acid (D-GalA) thioglycoside and the construction of a potent immunomodulating glycosphingolipid are described. The key steps of the synthesis are an Evans aldol reaction between a C4 aldehyde and a PMB-protected glycolyloxazolidinone as well as a tandem-PMB-deprotection/cyclization to thioglycosides. The key glycosylation step is optimized by varying the anomeric leaving group, the activating agent, and the solvent system.",10.1021/ol800227b,2008-03-26,0.6705646831802153
Journal of Organic Chemistry,"Convergent Synthesis of (−)-Mirabazole C Using a Chloroimidazolidium Coupling Reagent, CIP","Convergent synthesis of (−)-mirabazole C ( 1 ), a tetra thiazoline/thiazole alkaloid isolated from blue-green alga, has been described. The successive thiazoline rings of (−)-mirabazole C were formed by a single-step cyclization mediated by TiCl 4 treatment of tripeptide amide 4 . Convergent synthesis of the key intermediate 33 derived from three 2-methylcysteine residues was first achieved using a newly developed coupling reagent, 2-chloro-1,3-dimethylimidazolidium hexafluorophosphate (CIP). The effectiveness of CIP for the coupling of α,α-dialkyl amino acids and the reaction pathway of the activation were clarified by the syntheses of model peptides containing an α,α-dimethylamino acid. A practical method of asymmetric synthesis of 2-methylcysteine by alkylation of 2,4- cis -oxazolidinone 23 has also been described.",10.1021/jo952285h,1996-01-01,0.6705640210070356
Synthesis,A Practical and Scalable Synthesis of (S)- and (R)-1-(Dimethoxyphosphoryl)allyl Methyl Carbonates,The preparation of ( S )- and ( R )-1-(dimethoxyphosphoryl)allyl methyl carbonates is achieved on multigram scale from commercially available dimethyl phosphite and acrolein in three steps. The key steps involve an asymmetric Pudovik reaction and enzyme-catalyzed kinetic resolution.,10.1055/s-0035-1560487,2015-10-21,0.6705588246743504
Synlett,A Concise Synthesis of (<i>S</i>)-γ-Fluoroleucine Ethyl Ester,"We report herein a six-step, chromatography-free, through-process for the asymmetric synthesis of (S)-γ-fluoroleucine ethyl ester sulfate salt (6) that proceeds in 25% overall yield from inexpensive ethyl glyoxylate. This approach features a Ti/Zn-catalyzed glyoxylate-ene reaction-olefin hydrofluorination-amine alkylation as key steps.",10.1055/s-2005-923593,2006-01-01,0.6705568356351652
Journal of the American Chemical Society,Total Synthesis of the Serine-Threonine Phosphatase Inhibitor Microcystin-LA,"Reversible protein phosphorylation, which is mediated by kinases and phosphatases, is a major control element of the cell. There is a diverse group of toxic natural products that inhibit certain phosphatases, thereby disrupting normal biochemical pathways. These toxins can be useful for dissecting the individual biochemical pathways associated with each of these enzymes. This Article describes the first total synthesis of one such toxin, the cyclic heptapeptide microcystin-LA. The synthesis features a convergent route that is amenable to analog preparation in the search for selective phosphatase inhibitors. A new route to the unusual amino acid Adda is described, which incorporates an efficient diastereoselective aspartate alkylation and diene synthesis via a Suzuki coupling reaction. This work also features an efficient preparation of an N -methylalanine containing peptide via a Horner−Emmons condensation and several difficult amino acid coupling reactions that relied heavily on Carpino's remarkable HATU reagent.",10.1021/ja961683e,1996-01-01,0.6705364261053526
Journal of Organic Chemistry,Asymmetric Synthesis of a Prostaglandin D<sub>2</sub>Receptor Antagonist,"An asymmetric synthesis was developed for the production of a prostaglandin D(2) receptor antagonist for the treatment of allergic rhinitis. The stereogenic center was set using asymmetric allylic alkylation chemistry, and the core of the structure was constructed via Pd-catalyzed N-cyclization/Heck methodology. The synthesis relies on a late stage indoline oxidation which does not racemize the product.",10.1021/jo048305+,2004-12-01,0.6705259500511087
Organic Letters,Routes to Advanced Intermediates in the Synthesis of Tetracarbocyclic Sesquiterpenoids Daphnenoid A and Artatrovirenols A and B,"High Resolution Image Download MS PowerPoint Slide A short route from dihydrocarvone is described, which led to the tetracarbocyclic core common to artatrovirenol A and B and daphnenoid A. A variant of this route afforded guaia-4,6-dien-3-one (from Enterospermum madagascarensis ) and its epimer. From 2-(2-oxoethyl)furan, a 15-step sequence then delivered the complete carbon skeleton and all functionality necessary for daphnenoid A. Key steps in the route include diastereoselective intramolecular oxidopyrylium cycloaddition, oxa-bridge cleavage under “push–pull” conditions, and intramolecular Diels–Alder cycloaddition.",10.1021/acs.orglett.3c04199,2024-02-19,0.6705132304406634
Organic Process Research & Development,Development of a Nitrene-Type Rearrangement for the Commercial Route of the JAK1 Inhibitor Abrocitinib,"The development of a commercial route toward the JAK1 inhibitor abrocitinib is described. The application of a late-stage Lossen rearrangement provided the desired cis -diaminocyclobutane, which was subsequently sulfonylated using a novel water-tolerable triazole sulfonylating reagent to provide the active pharmaceutical ingredient.",10.1021/acs.oprd.0c00366,2020-09-18,0.6705014894479439
Synthesis,Synthesis of 4-Halogenated 3-Fluoro-6-methoxyquinolines: Key Building Blocks for the Synthesis of Antibiotics,"A practical and scalable 4-step route is presented for the synthesis of 4-bromo-3-fluoro-6-methoxyoquinoline and 3-fluoro-4-iodo-6-methoxyoquinoline from readily available 2,4-dichloro-3-fluoroquinoline with an overall yield of 81–85%. Halogenated quinoline building blocks have found much use in antimicrobial drug discovery, and the method reported here would be useful for the synthesis of these compounds.",10.1055/s-0034-1378554,2014-08-28,0.6704910851717065
Journal of the American Chemical Society,Convergent Total Synthesis of (−)-Cyclopamine,"A concise and enantioselective total synthesis of the Veratrum alkaloid cyclopamine is disclosed. This highly convergent synthesis with a 16-step longest linear sequence (LLS) was enabled by a de novo synthesis of the trans -6,5-heterobicycle via a strain-inducing halocyclization process, a key Tsuji–Trost cyclization to construct the fully substituted, spirocyclic THF motif with exquisite diastereocontrol, and a late-stage ring-closing metathesis (RCM) reaction to forge the central tetrasubstituted olefin.",10.1021/jacs.3c09085,2023-10-02,0.6704531994285087
Synthesis,"A Concise Synthesis of (S)-2-(Fluorodiphenylmethyl)pyrrolidine: A Novel Organocatalyst for the Stereoselective Epoxidation of α,β-Unsaturated Aldehydes","A concise synthesis of (S)-2-(fluorodiphenylmethyl)pyrrolidine from cheap, commercially available starting materials is described. Pertinent features of this synthetic route include ease of synthesis, facile purification steps, and an operationally simple deoxy­fluorination step to install the C-F bond.",10.1055/s-0029-1218636,2010-01-08,0.6704353051993059
Organic Process Research & Development,Development of a Kilogram-Scale Manufacturing Route for Bis-Tac-dG: Essential Building-Block for Guadecitabine,"Guadecitabine (SGI-110) is a dinucleotide that is a prodrug of decitabine. The dinucleotide contains decitabine (top fragment) and 2′-deoxyguanosine ( 9; dG; bottom fragment) connected via a 3′ → 5′ phosphodiester bond. The manufacturing process of guadecitabine requires a large quantity of N 2, 3′- O -(4- tert -butylphenoxyacetyl)-protected dG ( 2; Bis-Tac-dG) to incorporate the bottom fragment. The protected 2 being a critical starting material of the dinucleotide imposes stringent quality requirements for its synthesis and isolation. Presented herein is the development work leading to a practical and scalable route for compound 2 starting from commercial dG. Salient features of the approach included one-pot protection of 5′-OH group of N 2 -Tac-dG ( 3 ) with 4,4′-dimethoxytrityl (DMT) group followed by 3′- O -Tac protection furnishing fully protected dG 8, thus reducing the cycle time with fewer isolation steps and lowering the solvent usage. Subsequently, cleavage of DMT group from 8 utilizing NaIO 4 enabled a mild, highly selective, and robust route to produce high purity (>99%) Bis-Tac-dG on kilogram-scale. The structure and origin of major impurities were determined by comparison with reference standards and carefully controlled to an acceptable level in compound 2 . The improved synthesis was scaled to prepare multiple ∼60 kg batches of 2 to supply all clinical studies up to phase III.",10.1021/acs.oprd.4c00073,2024-05-03,0.6704346667334987
Synthesis,"Studies on Macrocyclic Diterpenoids (XVII): Total Synthesis of (-)-Cembrene-A and (+)-3,4-Epoxycembrene-A by Titanium-Induced Carbonyl Coupling Reactions","All articles of this category Efficient total synthesis of ( R )-cembrene-A (1) and (+)-3,4-epoxycembrene-A (2) , two marine cembranoids, starting from ( E )-geranylacetone (6) and ( R )-limonene (7) are described. The key steps are the synthesis of olefin 12 from phosphonate 4 and optically active ketone 5 by the modified Wittig olefination, and the titanium-induced intramolecular coupling of oxo aldehyde 3 to afford cembrene-A (1) . The pinacol coupling of 3 yielded the diol 13 which was converted into 3,4-epoxycembrene-A (2) . Asymmetric syntheses of two manine cembranoids ( R )-cembrene-A and (+)-3,4-epoxycembrene-A from ( E )-geranylacetone and ( R )-limonene are described.",10.1055/s-1996-4290,1996-06-01,0.6704307972401777
Angewandte Chemie International Edition,Total Synthesis of (+)‐ and (±)‐Hosieine A,Described herein is a concise total synthesis of the highly potent nicotinic acetylcholine receptor ligand hosieine A in racemic and enantioenriched forms. The synthesis requires only seven steps and features a telescoped reaction sequence initiated by a gold-catalyzed Rautenstrauch reaction.,10.1002/anie.201804076,2018-05-03,0.6704119906125049
Journal of the American Chemical Society,A Highly Stereoselective and Practical Total Synthesis of the Tricyclic β-Lactam Antibiotic GV104326 (4-Methoxytrinem),"A novel and practical total synthesis of a tricyclic β-lactam antibiotic, GV104326 (4-methoxytrinem or Sanfetrinem) has been achieved in nine steps and about 33% overall yield from a commercially available acetoxyazetidinone chiron. A key step in the highly diastereoselective synthesis is a protonation of a zinc enolate complex which circumvents the use of enantiomerically pure ( S )-2-methoxycyclohexanone. A mechanistic rationale is presented and experimentally verified.",10.1021/ja962006n,1996-01-01,0.670384479417256
European Journal of Organic Chemistry,Asymmetric Synthesis of the C14–C26 Building Block of Eribulin Mesylate,Abstract An alternative route for the synthesis of the C14–C26 building block of the anticancer drug eribulin mesylate is described. The key steps involved in the synthesis are a Julia–Kocienski olefination between aldehyde 4 and sulfone 5 and a tandem Sharpless asymmetric dihydroxylation/S N 2 cyclisation reaction on mesyl compound 3 .,10.1002/ejoc.201201119,2012-10-29,0.6703764124514978
Organic Letters,Stereoselective Total Synthesis of the Dimeric Naphthoquinonopyrano-γ-lactone (−)-Crisamicin A: Introducing the Dimerization Site by a Late-Stage Hartwig Borylation,"The first stereoselective total synthesis of the dimeric naphthoquinonopyrano-γ-lactone (−)-crisamicin A was realized (13 steps, 5% overall yield). 1,4,5-Trimethoxynaphthalene, reached in five known steps, was brominated at C-3 to install a but-3-enoic ester by an ensuing Heck coupling. An asymmetric Sharpless dihydroxylation followed and gave a β-hydroxy-γ-lactone with >99.9% ee. Its OH substituent and acetaldehyde established the dihydropyran ring in a completely diastereoselective oxa-Pictet–Spengler cyclization. The 2,3-fused anisole moiety allowed the C 5 –H bond under Hartwig’s conditions to be borylated. This set the stage for engaging the resulting C 5 –B bond in an oxidative dimerization, which led to a binaphthohydroquinon-5-yl. The latter was advanced to synthetic crisamicin A by a double CAN oxidation (→ a binaphthoquinon-5-yl) and a double demethylation.",10.1021/acs.orglett.0c01078,2020-04-16,0.6703375332444488
Synthesis,A New Synthesis of Racemic Rosaprostol,"All articles of this category Rosaprostol, an antiulcer drug, was prepared in five steps and in 36% overall yield starting from 3-(dimethoxyphosphorylmethyl)cyclopent-2-enone ( 6 ). The regioselective alkylation of 6 at C(2) with methyl 7-iodoheptanoate and subsequent Horner-Wittig reaction with pentanal constitute the key steps of this total synthesis. rosaprostol - antiulcer drug - phosphonates - Horner-Wittig reaction - total synthesis",10.1055/s-2000-6316,2000-01-01,0.6703101987381201
Organic Process Research & Development,"A Facile, Six-Step Process for the Synthesis of (3<i>S</i>,5<i>S</i>)-3-Isopropyl-5-((2<i>S</i>,4<i>S</i>)-4-isopropyl-5-oxo-tetrahydrofuran-2-yl)-2-oxopyrrolidine-1-carboxylic Acid <i>tert</i>-Butyl Ester, The Key Synthetic Intermediate of Aliskiren","A facile, six-step process for the synthesis of (3 S,5 S )-3-isopropyl-5-((2 S,4 S )-4-isopropyl-5-oxotetrahydro- furan-2-yl)-2-oxopyrrolidine-1-carboxylic acid tert -butyl ester from ( S )-4-benzyloxazolidin-2-one 2 in an overall 50% yield is reported. The key transformations include: a highly efficient diastereoselective epoxidation, Lewis acid-catalyzed ring-opening with bromide, an S N 2 reaction using NaN 3, and a tandem reduction–cyclization reaction.",10.1021/acs.oprd.5b00009,2015-05-21,0.6703076195094908
Organic Letters,Substituted Imidazoline Synthesis: A Diastereo- and Enantioselective aza-Henry Route to a Human Proteasome Modulator,"The first enantio- and diastereoselective synthesis of Tepe’s human proteasome modulator is described. Routes to this and other highly substituted chiral imidazolines generally produce racemic material. Key to the route disclosed here is a gram-scale anti -selective aza-Henry reaction of an α-alkyl α-nitro ester nucleophile, catalyzed by a Bis(Amidine) [BAM] chiral proton complex, delivering the key intermediate in high yield as a single stereoisomer. The adduct is reduced to the amino ester and converted to an imidazoline.",10.1021/acs.orglett.0c03096,2020-10-15,0.6703069740553086
Organic Process Research & Development,Development of the Enabling Route for Glecaprevir via Ring-Closing Metathesis,"Glecaprevir was identified as a potent HCV NS3/4A protease inhibitor, and an enabling synthesis was required to support the preclinical evaluation and subsequent Phase I clinical trials. The enabling route to glecaprevir was established through further development of the medicinal chemistry route. The key steps in the synthesis involved a ring-closing metathesis (RCM) reaction to form the 18-membered macrocycle and a challenging fluorination step to form a key amino acid. The enabling route was successfully used to produce 41 kg of glecaprevir, sufficient to support the preclinical evaluation and early clinical development.",10.1021/acs.oprd.9b00469,2019-12-27,0.6703062051808812
Tetrahedron,Zirconium-mediated ring contraction: An efficient synthesis of enantiomerically pure key intermediate of carbocyclic oxetanocin,,10.1016/s0040-4039(00)60421-5,1993-11-01,0.6702920038520341
Tetrahedron,An efficient synthesis of N-benzyl-3-sulfonyl glutarimides. Formal synthesis of the aromatase inhibitor AG-1,,10.1016/s0040-4039(00)01845-1,2000-12-01,0.6702767787389098
Tetrahedron,"An efficient route to 5,5″-diaryl-2,2′:6′,2″-terpyridines through 2,6-bis(1,2,4-triazin-3-yl)pyridines",,10.1016/j.tetlet.2005.01.020,2005-01-27,0.670263016963322
Organic Process Research & Development,"Chirality Control in the Kilogram-Scale Manufacture of Single-Enantiomer CELMoDs: Synthesis of Iberdomide·BSA, Part 2",Iberdomide ( 1 ·HCl) is a cereblon E3 ligase-modulating drug (CELMoD) in clinical trials for the treatment of systemic lupus erythematosus (SLE) and relapsed and refractory multiple myeloma (MM). The enantioselective synthesis of iberdomide to supply clinical and development activities proceeds through the late-stage intermediate iberdomide BSA salt ( 1 ·BSA). The route features a reductive amination between a chiral isoglutamine and a salicylaldehyde derivative to form the isoindolinone core. The penultimate intermediate is prepared by phenol alkylation with a benzylic chloride that requires detailed understanding of reaction parameters to avoid overreaction of the product and concomitant stereochemical ablation. The chiral α-amidoglutarimide moiety is constructed from an acid-catalyzed intramolecular lactamization of an isoglutamine tert -butyl ester moiety with high retention of the enantiomeric ratio ( e.r. ). This process was demonstrated on a kilogram scale over multiple batches and serves as the basis for the commercial synthesis of iberdomide.,10.1021/acs.oprd.3c00314,2023-12-28,0.6702492426139066
Tetrahedron,Convergent total synthesis of the racemic HIF-1 inhibitor laurenditerpenol,,10.1016/j.tetlet.2008.05.116,2008-05-31,0.6702456228595036
Green Chemistry,"Industrially scalable and cost-effective synthesis of 1,3-cyclopentanediol with furfuryl alcohol from lignocellulose","A new route for the synthesis of renewable 1,3-cyclopentanediol was developed by rearrangement of furfuryl alcohol to 4-hydroxycyclopent-2-enone followed by hydrogenation.",10.1039/c6gc00341a,2016-01-01,0.6702400251865829
Organic Process Research & Development,"Route Selection and Process Development of a Multikilogram Route to the Inhaled A<sub>2a</sub> Agonist UK-432,097","This article describes the selection, process development, and scale-up of a synthetic route to a complex nucleoside analogue, the A 2a agonist UK-432,097 ( 1 ), that culminated in the manufacture of over 25 kg of the API. The key steps in the process were (1) a stereoselective glycosidation reaction; (2) a scalable bleach–TEMPO oxidation; and (3) an unusual elevated temperature crystallization process for the final API. The problems that were encountered with the scale-up of the route together with how they were overcome are also presented.",10.1021/op200365n,2012-02-10,0.6702399310491732
Tetrahedron,"New preparations of the N-methyl-D-aspartate receptor antagonist, 4-(3-phosphonopropyl)-2-piperazinecarboxylic acid (CPP)",,10.1016/s0040-4039(01)93739-6,1989-01-01,0.6702249340115315
Organic Letters,Bioinspired Gram-Scale Synthesis of Alstoscholarinoid B,"Herein, we describe a gram-scale synthesis of alstoscholarinoid B, a rearranged triterpenoid with potent antihyperuricemic bioactivity. This synthesis was inspired by the biogenetic hypothesis and achieved in seven steps from oleanolic acid with an overall yield of 51%.",10.1021/acs.orglett.3c01891,2023-08-01,0.6701957485788385
Organic Process Research & Development,Development of the Synthetic Route to PF-06878031 Part 2: Amide Reduction Route,"The target compound PF-06878031 is a key structural fragment of a range of oral late-stage glucagon-like peptide-1 receptor agonists (GLP-1-RA) under development in our laboratories for the indications of type 2 diabetes mellitus (T2DM) and weight loss. This article describes the identification of an amide reduction route, and development of a process, capable of delivering multikilo quantities of PF-06878031 . The process development afforded improved safety, higher yield, a reduced step count, and a significant cost reduction. The new process has been scaled up at multiple facilities to generate >1.5MT of high-purity PF-06878031 .",10.1021/acs.oprd.4c00054,2024-04-19,0.6701904150307549
Angewandte Chemie International Edition,Total Synthesis of (+)‐Fawcettidine,Alkaloids alchemy: A synthesis of the Lycopodium alkaloid (+)-fawcettidine (see structure) has been developed which requires 16 steps from (R)-(+)-pulegone as the chiral starting material. Key steps include a platinum(II)-catalyzed annulation reaction of a functionalized enamide and a one-pot Ramberg–Bäcklund process.,10.1002/anie.200800522,2008-04-22,0.6701903525125225
Organic Letters,Regioselective and Diastereoselective Amination with Use of Chlorosulfonyl Isocyanate:  A Short and Efficient Synthesis of (−)-Cytoxazone,"The total synthesis of (-)-cytoxazone 1 was achieved in six linear steps (34% overall yield) from p-anisaldehyde. The key steps in this route are the regioselective and stereoselective introduction of a N-protected amine group, using the CSI reaction of the anti-1,2-dimethyl ether 3, and the subsequent regioselective cyclization of the N-protected amino diol 13 to give the 2-oxazolidinone unit of (-)-cytoxazone 1. [reaction: see text]",10.1021/ol0515255,2005-08-12,0.6701711404311241
Organic Letters,Concise Synthesis of the Chemopreventitive Agent (±)-Deguelin via a Key 6-Endo Hydroarylation,[reaction: see text]. A concise total synthesis of (+/-)-deguelin was achieved with a longest linear sequence of six steps in 68% yield. A key step was the platinum-catalyzed 6-endo hydroarylation of an alkynone intermediate.,10.1021/ol035419j,2003-09-26,0.6701703864906529
Organic Process Research & Development,Process Development and Scale-up of a β-Secretase Inhibitor via a Stereospecific Jocic Reaction,A scalable process for the synthesis of a spiropiperidine β-secretase inhibitor is described. Key stereochemical transformations utilized are a diastereoselective trichloromethyl addition followed by an unprecedented stereospecific Jocic reaction with an aniline nucleophile. Simplified processing was developed for a Dieckmann cyclization/decarboxylation sequence to give a process suitable for the production of kilogram quantities of API.,10.1021/op400115g,2013-06-17,0.6701059363557016
Tetrahedron,"Enantiospecific total synthesis of (−)-allosamizoline, and aminocyclitol moiety of the insect chitinase inhibitor allosamidin",,10.1016/s0040-4039(00)92386-4,1991-09-01,0.6701040523864885
Synlett,"An Efficient Synthesis of (1<i>R</i>,4<i>S</i>)-1-Methyl-8-methoxy-3-(4-toluenesulfonyl)-2,3,4,5-tetrahydro-1,4-methano-3-benzazepine. A Formal Synthesis of (-)-Aphanorphine","We report a highly efficient synthesis of (1R,4S)-1-methyl-8-methoxy-3-(4-toluenesulfonyl)-2,3,4,5-tetrahydro-1,4-methano-3-benzazepine in six steps from 5. The present work constitutes a new formal synthesis of marine alkaloid (-)-aphanorphine.",10.1055/s-2003-42102,2003-01-01,0.6700526631921011
Angewandte Chemie International Edition,Total Synthesis of RNA‐Polymerase Inhibitor Ripostatin B and 15‐Deoxyripostatin A,"Keep me skipped: a highly convergent total synthesis of ripostatin B, an inhibitor of the bacterial RNA polymerase, is described. The key steps to construct and avoid isomerization of the skipped triene are a double Stille cross-coupling reaction and a ring-closing metathesis. Furthermore, 15-deoxyripostatin A, a stable and conformationally locked analogue of ripostatin A, was prepared and tested in vivo.",10.1002/anie.201108749,2012-02-29,0.6700474687258584
Synthesis,Short and Diastereoselective Total Synthesis of the Polyhydroxylated Pyrrolidine LAB-1: A Potent α-Glycosidase Inhibitor,"We described herein a total synthesis of 1,4-dideoxy-1,4-imino-l-arabinitol [(2S,3S,4S)-2-(hydroxymethyl)pyrrolidine-3,4-diol, LAB-1], a polyhydroxylated pyrrolidine, which has been demonstrated to be a selective and potent α-glycosidase inhibitor. The main features of our approach are its shortness, efficiency, and simplicity. The total synthesis was accomplished in 6 steps with an overall yield of 12%, starting from a chiral optically active Morita–Baylis–Hillman (MBH) adduct prepared (without epimerization), from Garner’s aldehyde. As far as we know, this is the first report describing the total synthesis of this biologically active pyrrolidine by exploring the synthetic versatility of a MBH adduct.",10.1055/s-0036-1590799,2017-07-27,0.6700464591205592
Organic Letters,Total Synthesis and Absolute Configuration of Raputindole A,"The first total synthesis of the bisindole alkaloid raputindole A from the rutaceous plant Raputia simulans is reported. The key step is a Au(I)-catalyzed cyclization that assembles the cyclopenta[f]indole tricycle from a 6-alkynylated indoline precursor. The isobutenyl side chain was installed by Suzuki-Miyaura cross-coupling, followed by a regioselective reduction employing LiDBB. Starting from 6-iodoindole, the sequence needs nine steps and provided (±)-raputindole A in 6.6% overall yield. The absolute configuration of the natural product (+)-raputindole A was determined by quantum chemical calculation of the ECD spectrum.",10.1021/acs.orglett.7b03014,2017-11-17,0.6699908640091081
Organic Process Research & Development,"Evolution of a Manufacturing Route to Omarigliptin, A Long-Acting DPP-4 Inhibitor for the Treatment of Type 2 Diabetes","High Resolution Image Download MS PowerPoint Slide Development of a convergent synthesis of omarigliptin (MK-3102) suitable for commercial manufacture is described. The target molecule is assembled through a diastereoselective reductive amination of a highly functionalized pyranone with a mesylated pyrazole followed by deprotection of a Boc group. The synthesis of the pyranone relies on three Ru-catalyzed reactions: (1) a DKR reduction of a rac -α-aminoketone to set the two contiguous stereogenic centers, (2) a cycloisomerization of a bis-homopropargylic alcohol to a dihydropyran, and, finally, (3) a Ru-catalyzed oxidation of a pyranol to the desired pyranone. The regioselective synthesis of a N -Boc-1-mesyl pyrazole fragment was achieved via base-promoted mesyl group isomerization to afford 30:1 selectivity. A highlight of the endgame process development is telescoping a Boc deprotection and reductive amination followed by direct crystallization of the penultimate from the reaction mixture. This avoids handling of an unstable, mutagenic 1-mesylpyrazole BSA salt used in the earlier multikilogram deliveries and improves the overall diastereoselectivity and efficiency of the route.",10.1021/acs.oprd.5b00267,2015-10-01,0.6699427666070298
Tetrahedron,"Stereoselective synthesis of 1,3--3,5--triols using a -1,3-asymmetric reduction: A novel route to -1,3-polyols",,10.1016/s0040-4039(00)99366-3,1989-01-01,0.6699300812321878
Tetrahedron,A one-step synthesis of the twistane ring system 8-acetoky-4-twistanone,,10.1016/s0040-4039(00)89758-0,1968-01-01,0.6699215507583832
Organic Letters,"A 1-Pot Synthesis of the SARS-CoV-2 M <sup>pro</sup> Inhibitor Nirmatrelvir, the Key Ingredient in Paxlovid","A newly devised route to the Pfizer drug nirmatrelvir is reported that reduces the overall sequence to a 1-pot process and relies on a commercially available, green coupling reagent, T3P. The overall yield of the targeted material, isolated as its MTBE solvate, is 64%.",10.1021/acs.orglett.2c03683,2022-12-07,0.6699127250546284
Organic Process Research & Development,"An Efficient Kilogram-Scale Synthesis of <i>N</i>,<i>N</i>′-Bis(4,6-disubstituted 1,3,5-triazin-2-yl)-4-aminophenetylamine","A practical large-scale synthesis was developed for the preparation of N, N ′-bis(4,6-disubstituted 1,3,5-triazin-2-yl)-4-aminophenethylamine derivatives exemplified by compound 2 . This route is a six-step procedure starting from commercially available cyanuric chloride and 3-( tert- butoxycarbonylamino) aniline based on the reactivity differences of the three chlorine atoms on the triazine ring. The optimized procedure was scaled up to give the final product 2 in an overall yield of 61% and 99.9% purity. These low-molecular weight compounds mimic the ability of protein A to bind to IgG antibody.",10.1021/op900202b,2009-10-01,0.6698752382833585
Organic Letters,"A Short, Scalable Synthesis of the Carbocyclic Core of the Anti-Angiogenic Cortistatins from (+)-Estrone by B-Ring Expansion","A rapid and scalable synthesis of the carbocyclic core of the potent antiangiogenic natural products, the cortistatins, is presented starting from readily available (+)-estrone. Key steps include a regio- and stereoselective benzylic cyanation and a Demjanov rearrangement.",10.1021/ol802328n,2008-10-30,0.6698664343104476
Journal of Organic Chemistry,Enantioselective Synthesis of Antiinfluenza Compound A-315675,"Drug discovery efforts at Abbott Laboratories have led to the identification of influenza neuraminidase inhibitor A-315675 (1) as a candidate for development as an antiinfluenza drug. A convergent, stereoselective synthesis of this highly functionalized pyrrolidine is reported that utilizes pyrrolinone 2 as the key intermediate. The C5, C6 stereochemistry was established through a diastereoselective condensation of chiral imine compound 3 with silyloxypyrrole 4 to give pyrrolinone 2. The stereochemical outcome of this reaction depended critically on the choice of the imine functional group (FG), with tritylsulfenyl and (R)-toluenesulfinyl providing the desired products in good yields as crystalline intermediates. Conversion of pyrrolinone 2 into 1 was accomplished in seven subsequent steps, including Michael addition of cis-1-propenylcuprate at C4 and introduction of a cyano group as a carboxylic acid equivalent at C2.",10.1021/jo0162890,2002-01-29,0.6698210680269766
Organic Letters,Enantioselective Total Syntheses of (+)-Ganocin A and (−)-Cochlearol B,"Herein, we report the total syntheses of (+)-ganocin A and (-)-cochlearol B, featuring pentacyclic skeletons, in optically active forms. We utilized asymmetric Corey-Bakshi-Shibata reduction, phenolic oxidative cyclization, the intramolecular radical cyclization-benzylic oxidative cyclization sequence, and intramolecular [2 + 2] photocycloaddition. These key steps enabled enantioselective access with the longest linear sequence of 17 steps and 9% overall yield for (+)-ganocin A and with 16 steps and 9% overall yield for (-)-cohlearol B.",10.1021/acs.orglett.3c03572,2023-11-13,0.6698195440937483
Organic Letters,New Route to the Ergoline Skeleton via Cyclization of 4-Unsubstituted Indoles,"A new route to the ergoline skeleton has been developed that does not require prior functionalization of the indole 4-position. The indole nucleus is introduced late in the synthesis to allow for eventual efficient introduction of substituents in this region. Key steps include Negishi coupling of a three-carbon chain to a bromonicotinate ester, Fischer indole synthesis to facilitate incorporation of substituents via phenylhydrazines, and Pd-catalyzed cyclization to form the ergoline C ring.",10.1021/ol400620a,2013-05-09,0.6698137480479036
European Journal of Organic Chemistry,A Preparative Synthesis of Human Chitinase Fluorogenic Substrate (4′‐Deoxychitobiosyl)‐4‐methylumbelliferone,"Abstract To meet the increasing clinical demand for the diagnostic agent (4′‐deoxychitobiosyl)‐4‐methylumbelliferone, a flexible and scalable route of synthesis is needed. In this paper such a route is presented. The key to the route is the use of a partially protected thiophenyl glucosamine as starting material for the preparation of both the reducing and nonreducing end building blocks of the 4′‐deoxychitobiose disaccharide.",10.1002/ejoc.201000080,2010-03-20,0.6697945157899947
Journal of Organic Chemistry,"Palladium-Catalyzed Intramolecular N-Arylation of Heteroarenes:  A Novel and Efficient Route to Benzimidazo[1,2-<i>a</i>]quinolines","An efficient new route for the synthesis of benzimidazo[1,2-a]quinolines has been developed via the palladium-catalyzed intramolecular Buchwald-Harwtig aryl amination of newly synthesized 2-(2'-bromoanilino)quinolines.",10.1021/jo0522411,2006-01-04,0.6697880886229721
European Journal of Organic Chemistry,Total Synthesis of Pseudellone C,"The first chemical synthesis of a bisindole alkaloid, pseudellone C, was achieved in 44 % overall yield. The highlighting features of the synthesis include the fact that it is protecting‐group free, economic and commercially available starting materials are used, and the pure product can be obtained on a gram scale through one single purification process. The key step of this synthesis is the formation of an amide bond between the two major cores of the natural product.",10.1002/ejoc.201700491,2017-05-17,0.669775337990637
Tetrahedron,"New and efficient synthesis of 5′-amino-5′-(S)-methyl-2′,5′-dideoxynucleosides",,10.1016/s0040-4039(02)02514-5,2003-01-01,0.6697385860605628
European Journal of Organic Chemistry,"Cicindeloine from <i>Stenus cicindeloides</i> – Isolation, Structure Elucidation, and Total Synthesis","Abstract The new piperideine alkaloid cicindeloine ( 3 ) was isolated from the pygidial glands of the beetles Stenus cicindeloides and Stenus solutus . The structure and absolute configuration of 3 were elucidated by NMR spectroscopy and asymmetric synthesis, respectively. A very efficient gram‐scale synthesis of 3 was developed using an intramolecular aza‐Wittig reaction as the final step. The synthetic route is comprised of 12 steps and proceeds in 20 % total yield. Nine of the 12 steps were conducted without column chromatography.",10.1002/ejoc.201101709,2012-02-03,0.6696157838075987
Synthesis,Total Synthesis of (+)-Clavulatriene A,"The protecting-group-free total synthesis of (+)-clavulatriene A has been achieved. Key features of the synthetic strategy include the development of a novel strategy for the practical synthesis of α-cyperone, and a one-pot palladium-catalyzed reductive desulfonylation and deacetoxylation reaction. Furthermore, the total synthesis described in this study allowed for the determination of the absolute configuration of (+)-clavulatriene A.",10.1055/s-0034-1379898,2015-03-05,0.6696141717320337
Synlett,A Short Synthetic Route to β-<i>C</i>-Glycosides of <i>N</i>-Acetylglucosamine,A short and efficient process is described for the synthesis of protected and unprotected 1-formyl-C-glycosides of N-acetylglucosamine.,10.1055/s-2006-939061,2006-04-24,0.6695838686080801
Journal of the American Chemical Society,A Short Enantioselective Total Synthesis of the Third-Generation Oral Contraceptive Desogestrel,"Desogestrel ( 1 ) has been synthesized enantioselectively by a 14-step process from the known and readily available precursor 3, as outlined in Chart 2. At the heart of this process is the short, convergent, and stereocontrolled method for forming the tetracyclic ring system and the critical 11-exomethylene function, that is, the sequence of steps 6 → 8 → → 12 . All steps of the synthesis proceed in good yield.",10.1021/ja983179a,1999-01-20,0.6695363917634752
Journal of Organic Chemistry,"Second-Generation, Highly Abbreviated Route for Elaboration of the Oxetane D-Ring in a Fully Functionalized Taxane",A six-step conversion of oxirane 3 to oxetane 9 is reported. The synthetic route takes particular advantage of the acid-catalyzed ring opening of 3 to allyl alcohol 4 in a polar reaction medium and of the heightened capability of the OsO4.TMEDA complex to effect the efficient stereocontrolled dihydroxylation of this intermediate. The overall yield of the new sequence is 33%.,10.1021/jo0482965,2004-12-23,0.66947501026127
Journal of Organic Chemistry,Total Synthesis of (+)-Demethoxycardinalin 3,The total synthesis of (+)-demethoxycardinalin 3 is described. The synthetic strategy features the synthesis of dimeric Fischer carbene and its use in a bidirectional Dötz benzannulation reaction to set the dimeric structure of the cardinalins. The oxa-Pictet-Spengler reaction was used to construct the pyran rings. The synthesis is completed in seven steps and an overall yield of 7%.,10.1021/jo101628m,2010-09-17,0.6694102356953039
Tetrahedron,An improved approach to the synthesis of adenosine-5′-N-ethyluronamides of interest as adenosine receptor agonists,,10.1016/0040-4039(96)00092-5,1996-03-01,0.6694071531216512
Angewandte Chemie International Edition,"An Efficient Stereoselective Total Synthesis of dl-Sesquicillin, a Glucocorticoid Antagonist",The key step in the total synthesis of sesquicillin (3) is a stereoselective Claisen rearrangement of 1 to afford 2. The synthesis also features an efficient sequence to install an α-pyrone moiety in a hindered environment; TBS = tert-butyldimethylsilyl.,10.1002/1521-3773(20020415)41:8<1434::aid-anie1434>3.0.co;2-a,2002-04-15,0.6693894670269609
Tetrahedron,Highly stereoselective and practical synthesis of a key intermediate for 1-β-methylcarbapenems,,10.1016/0040-4039(96)00980-x,1996-07-01,0.6693777460869594
Tetrahedron,A new stereoselective synthetic route to perhydrohistrionicotoxin,,10.1016/s0040-4039(01)82974-9,1981-01-01,0.6693641232909895
Tetrahedron,A new and efficient route for the synthesis of alkynyl functionalized silicon derivatives,,10.1016/j.tetlet.2013.11.103,2013-12-01,0.6693556834303506
Journal of Organic Chemistry,"Efficient Synthesis of Novel NK<sub>1</sub> Receptor Antagonists:  Selective 1,4-Addition of Grignard Reagents to 6-Chloronicotinic Acid Derivatives","A new efficient synthesis of two novel classes of NK1 receptor antagonists, among them befetupitant and netupitant, starting from 6-chloronicotinic acid is described. The introduction of the o-tolyl substituent at C4 of the pyridine ring was achieved by a one-pot selective 1,4-Grignard addition/oxidation sequence to 6-chloronicotinic acid or a derivative of it. The scope of this addition/oxidation sequence was examined. It was also shown that the carboxylic function can be converted to a methyl amino group by a Hofmann rearrangement followed by reduction. Furthermore, a new high-yielding synthesis of 2-(3,5-bistrifluoromethylphenyl)-2-methyl propionic acid based on the carbonylation of the tertiary alcohol obtained by Grignard addition of 3,5-bis(trifluoromethyl)bromobenzene to acetone was established.",10.1021/jo0523666,2006-02-09,0.6693452187541913
European Journal of Organic Chemistry,Asymmetric Synthesis of (+)‐Tanikolide and the β‐Methyl‐Substituted Analogues of (+)‐Tanikolide and (–)‐Malyngolide,"Abstract The δ‐lactone‐containing natural product (+)‐tanikolide, a brine shrimp toxin and antifungal compound, was synthesized in nine steps with an overall yield of 26.4 % by employing Sharpless asymmetric epoxidation and ZrCl 4 ‐catalyzed intramolecular acetalization as the key steps. The novel β‐methyl‐substituted analogues of (+)‐tanikolide and(–)‐malyngolide have also been prepared by using the same asymmetric synthetic approach.",10.1002/ejoc.201101190,2011-10-19,0.6693339491410764
Tetrahedron,"Novel and practical asymmetric synthesis of an azetidine alkaloid, penaresidin B",,10.1016/s0040-4039(02)02743-0,2003-01-01,0.6693060042445569
Organic Process Research & Development,"A Simplified Process for the Manufacture of AZD0530, a Potent SRC Kinase Inhibitor","An efficient process for the manufacture of AZD0530 1, a potent SRC kinase inhibitor, has been developed. The key transformation, reaction of monofluoroanilide 7 with alcohol 8, was much simplified between manufacturing campaigns. The development of a robust, efficient, and scalable process for this transformation drew on both a practical and theoretical understanding of the process and is described herein",10.1021/op200079g,2011-04-20,0.6692751775199894
Angewandte Chemie International Edition,"Gephyronic Acid, a Missing Link between Polyketide Inhibitors of Eukaryotic Protein Synthesis (Part II): Total Synthesis of Gephyronic Acid","19 steps in the longest linear sequence are required in the 27 step total synthesis of gephyronic acid. A key step is a diastereodifferentiating Mukaiyama aldol reaction of an aldehyde and an enolsilane (see picture, PG: protecting group). The strongly cytotoxic target compound is a structural relative of the polyketide tedanolide and was isolated from the myxobacterium Archangium gephyra.",10.1002/anie.201005605,2010-12-29,0.6692539931156413
Tetrahedron,"Synthesis of (±)-pyranonaphthoquinone derivatives, a Cdc25A phosphatase inhibitor",,10.1016/j.tetlet.2003.11.120,2003-12-22,0.6692196631017054
Tetrahedron,A highly convergent strategy for the synthesis of 4-demethoxydaunomycinone and daunohycinone: A novel synthesis of C4-acetoxylated homophthalic anhydrides,,10.1016/s0040-4039(00)83975-1,1986-01-01,0.6692027213357625
Journal of Organic Chemistry,"Synthesis of Oxazolo[4,5-<i>c</i>]quinoline TRPV1 Antagonists","An efficient synthesis of 2-amino-oxazolo[4,5-c]quinoline TRPV1 antagonists is described via a thiourea formation/carbodiimide cyclization sequence. Synthetic route optimization eliminates intermediate isolations and facilitates the rapid preparation of a series of novel pentacyclic TRPV1 antagonists. From this series, compound (S)-4 was identified as a potent and selective ligand for the TRPV1 ion channel.",10.1021/jo101938b,2010-11-23,0.6691957249401012
Synlett,Synthesis of Polyhydroxylated Conidine Alkaloid as a Conformationally Restricted Azasugar,A conformationally restricted polyhydroxylated 1-azabicy­clo[4.2.0]octane core has been synthesized in search for a potent selective glycosidase inhibitor. The key feature of the synthesis involves the high stereoselective photoelectron-transfer-promoted cyclization of the strained α-trimethylsilylmethylazetidine moiety to the tethered π functionality.,10.1055/s-0036-1588312,2016-09-06,0.6691854142325753
Organic Process Research & Development,"Convergent, Kilogram Scale Synthesis of an Akt Kinase Inhibitor","The development of a convergent, chromatography-free synthesis of an allosteric Akt kinase inhibitor is described. The route comprised 17 total steps and was used to produce kilogram quantities of the target molecule. A key early transformation, for which both batch and flow protocols were developed, was formylation of a dianion derived by deprotonation and subsequent lithium-halogen exchange from a 2-bromo-3-aminopyridine precursor. Improved reaction yield and practicality were achieved in the continuous processing mode. Further significant process developments included the safe execution of a high temperature and pressure hydrazine displacement, separation of substituted cyclobutane diastereomers by means of chemoselective ester hydrolysis, and a late-stage Suzuki fragment coupling under mild conditions.",10.1021/op300031r,2012-03-23,0.6691539380017232
Synthesis,"A Facile Synthesis of 2-Aminopropane-1,2,3-tricarboxylic Acid and Its Symmetrical Dimethyl Ester","Abstract A new convenient synthetic route to 2-aminopropane-1,2,3-tricarboxylic acid is described. The first two stages of the three-step synthesis are performed in a one-pot procedure and include the cyclization of hippuric acid with DCC followed by treatment with methyl bromoacetate to yield an alkylated oxazolone. Its hydrolysis with HCl provides 2-aminopropane-1,2,3-tricarboxylic acid as its HCl salt. Esterification of the resulting acid with methanol in the presence of thionyl chloride leads selectively to its symmetrical diester.",10.1055/s-0040-1720389,2021-08-10,0.6691420348489191
Organic Process Research & Development,Process R&amp;D of Eravacycline: The First Fully Synthetic Fluorocycline in Clinical Development,Process research and development of the first fully synthetic broad spectrum 7-fluorotetracycline in clinical development is described. The process utilizes two key intermediates in a convergent approach. The key transformation is a Michael–Dieckmann reaction between a suitable substituted aromatic moiety and a key cyclohexenone derivative. Subsequent deprotection and acylation provide the desired active pharmaceutical ingredient in good overall yield.,10.1021/op4000219,2013-04-06,0.669141443393788
Organic Letters,Studies toward the Total Synthesis of Popolohuanone E:  Enantioselective Synthesis of 8-<i>O</i>-MethylpopolohuanoneE,[structure: see text]. 8-O-methylpopolohuanone E (2) was synthesized in a highly convergent manner starting from the cis-fused decalin derivative accessible from the (-)-Wieland-Miescher ketone analogue. The synthetic method features a biogenetic-type annulation of the phenolic and quinone segments to regioselectively construct the central tricyclic ring system as the key step.,10.1021/ol016285h,2001-07-26,0.669080884935246
Synthesis,Studies of the Asymmetric Total Synthesis of Clavilactone D by the ‘Lariat’ Cyclization Strategy,"A route to the core structure of clavilactone D, a new member of the tyrosine kinase inhibitors, is reported. The route employs sequential cyclization initiated by iodo etherification followed by Friedel-Crafts cyclization to furnish a polycyclic lactone fused with an aromatic ring, which is readily transformed into the proposed clavilactone scaffold.",10.1055/s-0029-1216909,2009-07-23,0.6690198154538075
Organic Process Research & Development,"Improved Process for Preparation of (3<i>R</i>,4<i>R</i>)-3-(3,4-Dimethyl-4-piperidinyl)phenol, A Key Intermediate for the Synthesis of Alvimopan","This report discloses an industrially feasible and cost efficient process for the preparation of the compound [(3 R, 4 R )-3-(3,4-dimethyl-4-piperidinyl)phenol] ( 1 ), which is used as the key intermediate for preparation of the opioid drug Alvimopan. The overall yield in this process is increased from 15 to 30%, mainly due to the improvement in yield from 26 to 53% for intermediate 7 .",10.1021/op400144z,2013-12-23,0.6689592234774329
Organic Letters,Synthesis of a Ketone Analogue of Biotin via the Intramolecular Pauson−Khand Reaction,"We report an improved synthesis of 5-(5-oxohexahydrocyclopenta[c]thiophen-1-yl)pentanoic acid (ketone biotin, 1) based on the intramolecular Pauson-Khand cyclization. The synthesis proceeds in eight steps and in 2.7% overall yield from cyclohexene.",10.1021/ol061862t,2006-09-01,0.6689429613506193
Organic Letters,A Four-Step Total Synthesis of Radermachol,Radermachol has been synthesized in four steps and an overall yield of 22% via key ytterbium triflate catalyzed furannulation and intramolecular nucleophilic acylation reactions.,10.1021/ol500862w,2014-04-21,0.6689249200078353
Synthesis,"Total Synthesis of the Natural Carbazoles Murrayanine and Murrayafoline A, Based on the Regioselective Diels-Alder Addition of<i>exo</i>-2-Oxazolidinone Dienes","A new synthesis of the natural carbazoles Murrayanine (1) and Murrayafoline A (3) is described. The key step in the synthetic route involved the regioselective cycloaddition of the diene 4,5-dimethylene-3-phenyl-1,3-oxazolidin-2-one (4) to acrolein (6) catalyzed by Lewis acids at low temperature. Direct aromatization of the substituted cyclohexene moiety of adduct 7, and further hydrolysis of the 2-oxazolidinone ring, proved to be a more efficient strategy than the opposite synthetic sequence for the preparation of the corresponding arylphenylamines 14 and 18. Palladium-promoted cyclization of the latter furnished the desired carbazoles 1 and 3 in high overall yields.",10.1055/s-2004-831213,2004-01-01,0.6688763932118119
Journal of Organic Chemistry,Highly Diastereoselective Synthesis of Pederic Acid Derivatives,"A highly diastereoselective synthesis of methyl pederate (2) is described. A critical feature of the successful route is the introduction of the key C(7)-stereocenter at the stage of 4 via an enantioselective, syn-selective aldol reaction of aldehyde 5 and the chiral acyl oxazolidinone 6. Aldehyde 5, in turn, was prepared from the readily available aldol derivative 7 via a chelate-controlled reaction with allyltrimethylsilane. Intermediate 4 was elaborated to 2 via the intermediacy of 7-O-(3,4-dimethoxybenzyl)pederic acid (3), an intermediate in Kishi's syntheses of mycalamides A and B and onnamide A, by way of methyl pyranoside 10 and the fully protected pederic acid derivative 11.",10.1021/jo961841k,1997-02-01,0.6688703540543064
Synlett,Selective and Gram-Scale Synthesis of [6]Cycloparaphenylene,"A selective, practical, and large-scale synthesis of [6]cycloparaphenylene, the second smallest cycloparaphenylene to be synthesized, was achieved in nine steps starting from commercially available 1,4-dibromobenzene and 4′-bromobiphenyl-4-ol. The key intermediate, cis -1,4-(4-bromophenyl)-1,4-bis(triethylsiloxy)cyclohexa-2,5-diene, was prepared on a large scale (>20 g) and was selectively dimerized to form a cyclic precursor of [6]cycloparaphenylene by platinum-mediated assembly and subsequent reductive elimination. Deprotection of the triethylsilyl group and subsequent tetrachlorostannic acid (H 2 SnCl 4 )-mediated reductive aromatization gave [6]cycloparaphenylene in 23% overall yield from the commercially available substrates on gram scale.",10.1055/s-0034-1380714,2015-05-20,0.6688594561611976
Organic Process Research & Development,Efficient Multigram-Scale Synthesis of 7-Substituted 3-Methyltetral-1-ones and 6-Fluoromenadione,"Herein, we report a safe and economical multigram synthesis of 6-fluoromenadione, an intermediate in the synthesis of novel biologically active agents. The key to this six-step sequence process involves the condensation of the readily available starting 4′-fluoropropiophenone and glyoxylic acid, a bromination–elimination sequence from 7-fluoro-3-methyltetral-1-one allowing aromatization of the naphthol intermediate, which is then oxidized into the corresponding 6-fluoromenadione. The multigram process has been demonstrated from 25 g of starting material scale with an improved overall yield of 50% and then applied to five other 7-substituted 3-methyltetralones and their corresponding 6-substituted menadiones.",10.1021/acs.oprd.1c00421,2022-02-15,0.6688441945129486
Tetrahedron,A new and practical synthesis of indolones,,10.1016/0040-4039(94)88509-5,1994-12-01,0.668844023892917
Tetrahedron,"New and practical synthesis of 1,4-dihydrobenzopyrano-pyrazoles",,10.1016/s0040-4039(01)01328-4,2001-09-01,0.668844023892917
Tetrahedron,A new and practical synthesis of pyrroles,,10.1016/0040-4039(95)02001-2,1995-12-01,0.668844023892917
Tetrahedron,New practical synthesis of spirocyclopentenones,,10.1016/s0040-4039(00)77687-8,1992-01-01,0.668844023892917
Organic Process Research & Development,Kilogram-Scale Synthesis and Impurity Profiling of a COPD Candidate <b>LY104</b>: Optimization of Salt Forms for Enhanced Purity and Pharmaceutical Potential,"This study describes a synthetic route to access LY104, a structurally novel compound investigated for the treatment of chronic obstructive pulmonary disease (COPD). Our approach to LY104 encompasses (i) a concise and efficient synthetic strategy for this COPD candidate and (ii) a scalable process with structural characterization of related impurities. The synthesis of LY104 was accomplished in four steps, during which three key impurity structures were identified. Through careful optimization of the chemical process, LY104 acetate salt was consistently obtained in a high purity (>99.85%) for pharmacological studies.",10.1021/acs.oprd.5c00123,2025-06-16,0.6688431589199437
European Journal of Organic Chemistry,Late‐Stage β‐Epimerization. A Stereodivergent to Stereoconvergent Relay to the First Total Synthesis of (+)‐Murolic Acid,"Abstract The first total synthesis of (+)‐murolic acid is accomplished in 17 steps from ester 9 in 14.8 % overall yield. The key steps involve asymmetric dihydroxylation, orthoester Johnson–Claisen rearrangement and α‐methylenation using Stiles reagent. A beneficial late stage β‐epimerization reverted a stereodivergent relay to a stereoconvergent completion of an efficient synthesis of (+)‐murolic acid.",10.1002/ejoc.201301287,2013-11-28,0.6688102766080303
Journal of Organic Chemistry,Enantioselective Approach to Quinolizidines: Total Synthesis of Cermizine D and Formal Syntheses of Senepodine G and Cermizine C,"The formal syntheses of C5-epi-senepodine G and C5-epi-cermizine C have been accomplished through a novel diastereoselective, intramolecular amide Michael addition process. The total synthesis of cermizine D has been achieved through use of an organocatalyzed, heteroatom Michael addition to access a common intermediate. Additional key steps of this sequence include a matched, diastereoselective alkylation with an iodomethylphenyl sulfide and sulfone-aldehyde coupling/reductive desulfurization sequence to combine the major subunits. The utility of a Hartwig-style C-N coupling has been explored on functionally dense coupling partners. Diastereoselective conjugate additions to α,β-unsaturated sulfones have been investigated, which provided the key sulfone intermediate in just six steps from commercially available starting materials. The formal syntheses of senepodine G and cermizine C have been accomplished through an intramolecular cyclization process of a N-Boc-protected piperidine sulfone.",10.1021/jo400324t,2013-04-29,0.6687884492712369
Journal of Organic Chemistry,Enantioselective Synthesis of the AB-Ring System of the Antitumor Antibiotic Tetrazomine,"The synthesis of the 1,2,3,4-tetrahydroisoquinoline moiety of tetrazomine was accomplished in 18 steps and in 3% overall yield from commercially available o-anisaldehyde. The reaction sequence utilizes a Sharpless asymmetric dihydroxylation to install the stereocenter and an intramolecular Friedel--Crafts hydroxyalkylation with an N-protected 2-oxo-acetamide to close the heterocyclic ring.",10.1021/jo015512q,2001-03-28,0.6687873845542863
Synthesis,"New Route to the 5,12-Dihydro-7<i>H</i>-benzo[2,3]azepino[4,5-<i>b</i>]indol-6-one Core via a Tin-Mediated Indole Synthesis","A new route to the paullone scaffold was designed. The key step consisted in a free radical indole formation from an o-al­kenyl arylisonitrile followed by Stille coupling with N-Boc-o-iodo­aniline. After deprotection and closure of the seven-membered ring by lactamisation, parent or cyano-substituted paullones were obtained in moderate to good yields.",10.1055/s-2006-950328,2006-11-01,0.6687080955989421
Journal of the American Chemical Society,"Total Synthesis of Landomycin A, a Potent Antitumor Angucycline Antibiotic","The first total synthesis of landomycin A, the longest and most potent antitumor angucycline antibiotic, has been achieved in 63 steps and 0.34% overall yield starting from 2,5-dihydroxybenzoic acid, 3,5-dimethylphenol, triacetyl d-glucal, and d-xylose, with a convergent linear sequence of 21 steps.",10.1021/ja205339p,2011-07-25,0.668673663446737
Journal of Organic Chemistry,A Highly Stereoselective Asymmetric Synthesis of (−)-Lobeline and (−)-Sedamine,"A highly stereoselective asymmetric synthesis of (--)-sedamine and (--)-lobeline is described from benzaldehyde in 16 and 17 steps with an overall yield of 20% and 14%, respectively. The key intermediate syn-3,4-epoxyalcohol was prepared in a highly diastereomeric fashion (>99% ee, dr) and served as a common intermediate for both alkaloids.",10.1021/jo020501y,2002-12-01,0.6686606389900275
Journal of Organic Chemistry,Total Synthesis of Dactylicapnosines A and B,"Dactylicapnosines A and B, two natural products from Dactylicapnos scandens, exhibited potent anti-inflammatory and analgesic activities both in vitro and in vivo. In this paper, we report our second-generation synthesis of dactylicapnosine A and the first total synthesis of dactylicapnosine B. Our synthetic route features acid-induced isomerization of o -quinone ( 16 ), Co-mediated regioselective ring contraction of p -quinone ( 8b ), and oxidative methoxylation of enone ( 18 ). This modified sequence provides dactylicapnosine A in 14 steps with an overall yield of 12% from a known compound ( 14a ) and also offers opportunities to synthesize dactylicapnosine-like analogues for biological investigations.",10.1021/acs.joc.0c01900,2020-10-20,0.6686518047393891
Organic Process Research & Development,"A Radical Addition Approach to a Heptafluoroisopropyl Substituted Arene, Combined with a Highly Diastereoselective Annulation Reaction To Synthesize the Tricyclic Core of BMS-986251","We have devised an asymmetric route to the tricyclic core 10 of BMS-986251. The six-step synthesis utilizes readily available starting materials, involves the one-step installation of the perfluoro isopropyl moiety through a radical mechanism, and leverages a novel diastereoselective annulation to build the pyrrolidine ring. Overall, 10 was obtained in 49% yield as a single stereoisomer in 6 steps and 3 isolations using this new route.",10.1021/acs.oprd.1c00338,2021-11-11,0.668555684809848
Journal of Organic Chemistry,A New Synthesis of 2-Azabicyclo[2.1.1]hexanes,"An efficient synthesis of the 2-azabicyclo[2.1.1]hexane ring system has been accomplished starting from cis-cyclobut-3-ene-1,2-dicarboxylic anhydride 7, which was prepared using a photochemical method. The key step of this new strategy involved a stereoselective electrophilic addition of phenylselenyl bromide to the double bond of cyclobutene dicarbamate 16 derived from 7. The subsequent ring closure of 17a in the presence of sodium hydride afforded the 2-azabicyclohexane compound 18 with a satisfying overall yield. Reductive removal of the phenylselenyl group and subsequent deprotection led rapidly to the amino derivative 4a functionalized on the carbon ring. Syntheses of the hydroxy and carboxylic derivatives 4b,c were then achieved from the intermediary disulfonamide 23. Displacement of the activated amino group by potassium acetate yielded hydroxy derivative 4b after three additional steps. Finally, oxidation of the alcohol function of 4b under Jones conditions followed by hydrogenolysis afforded the carboxylic derivative 4c, which is the first reported beta-isomer of 2,4-methanoproline 1.",10.1021/jo001790y,2001-05-17,0.6685545227439991
Journal of Organic Chemistry,A Concise and Convergent Synthesis of PA-824,"An efficient four-step synthesis of PA-824, a promising antituberculosis drug candidate, has been developed. This concise approach offers significant improvements over the synthetic route currently used for large-scale production.",10.1021/jo1015807,2010-10-07,0.6685424980318065
Synthesis,Stereoselective Synthesis of (+)-Polyoxamic Acid Starting with a Chiral Aziridine,"An efficient and stereoselective synthesis of (+)-polyoxamic acid was developed. The route starts with the commercially available 1-( R )-α-methylbenzylaziridine-2-methanol, a substance that has not been used previously as a starting material for the preparation of this target. The route also features the use of a stereocontrolled Sharpless asymmetric dihydroxylation reaction, promoted by AD-mix-α, which is followed by a regioselective aziridine ring-opening process, to generate the basic skeleton of target natural product. Subsequent oxidation and global deprotection produces (+)-polyoxamic acid.",10.1055/s-0033-1338545,2013-09-26,0.6685057837700702
Organic Process Research & Development,A Novel Method for the Large Scale Synthesis of Cinacalcet Hydrochloride Using Iron Catalyzed C–C Coupling,"A novel synthetic route for commercial preparation of cinacalcet hydrochloride ( 1 ), a calcimimetic agent and calcium-sensing receptor antagonist, is described. Our synthetic approach involves the preparation of cinacalcet using C–C bond formation catalyzed by iron acetylacetonate/NMP complex with aryl Grignard reagent benzotrifluoride magnesium bromide ( 8 ) and alkenyl halide N -chloropropene naphthylethylamine ( 6 ).",10.1021/op300164y,2012-08-31,0.6684790432044153
Organic Letters,Total Synthesis of (−)-Histrionicotoxin 285A and (−)-Perhydrohistrionicotoxin,"Starting from commercially available ( S)-glycidol, and via a common intermediate, the total synthesis of (-)-histrionicotoxin 285A and (-)-perhydrohistrionicotoxin has been achieved. Key to this synthesis was the efficient construction of a six-membered, chiral, cyclic nitrone.",10.1021/ol801604z,2008-09-03,0.668449305862688
European Journal of Organic Chemistry,A General Convergent Strategy for the Synthesis of Tetra‐Substituted Furan Fatty Acids (FuFAs),"Using a palladium catalyzed ‐ acid mediated isomerization sequence, tetrasubstituted furans suitable for furan fatty acid (FuFA) total synthesis can be effectively constructed in high yield. This convergent approach installs the essential carbon side chains at the α 1 ‐ and α 2 ‐positions, the β 1 ‐methyl group, and importantly, an electron withdrawing group at the β 2 ‐position tempering the reactivity of the electron rich furan in the FuFAs. When this EWG is an ester, it was conveniently transformed into the required β 1 ‐methyl group in three high yielding synthetic steps. Using this approach, the total synthesis of 11D5 and 11D3 was accomplished in 7‐steps from commercially available starting materials in overall yields of 52 % and 48 %, respectively. Furthermore, this methodology also provided an efficient synthetic route to the decarboxy analogues of both 11D5 and 11D3.",10.1002/ejoc.202000234,2020-03-20,0.6684478588722337
Journal of Organic Chemistry,Total synthesis of the novel coenyzme methoxatin,A convergent total synthesis of the novel coenzyme methoxatin is described. This coenzyme is a pyrroloquinoline quinone tailored for efficient oxidation of methanol and formaldehyde in methylotrophic bacteria. The synthesis was achieved by joining a pyrrole subunit with uvitonic acid ester followed by photocyclization of the resulting olefin to deoxymethoxatin 10. Conversion of 10 to methoxatin proceeded in five steps and led to some elaboration of the chemistry of the unusual pyrroloquinoline heterocycle. The overall yield is ~15% in 11 operations.,10.1021/jo00210a024,1985-05-01,0.6684469544148085
Synthesis,First Total Synthesis of (±)-Rhodoconferimide,"Starting from vanillin and dimethyl maleate, a concise and efficient racemic total synthesis of the potent antioxidant marine natural product (±)-rhodoconferimide has been carried out via the Wittig reaction, catalytic hydrogenation, selective brominations, and imide formation. An appropriate regioselective double bromination of the aromatic ring was a key step in the synthesis.",10.1055/s-0036-1590944,2017-11-06,0.6684422561210944
Angewandte Chemie International Edition,Total Synthesis of the Marine Natural Product (−)‐Cribrostatin 4 (Renieramycin H),"Winning at dominoes: The cytotoxic title compound was synthesized from five readily available starting materials in a longest linear sequence of 21 steps and 4.3 % overall yield. The key step in the construction of the pentacyclic core of 1 was a domino sequence involving β elimination and an intramolecular phenolic Mannich reaction. Alloc=allyloxycarbonyl, Bn=benzyl, Boc=tert-butoxycarbonyl.",10.1002/anie.200700539,2007-04-17,0.6684141190152053
Journal of Organic Chemistry,Conversion of a Benzofuran Ester to an Amide through an Enamine Lactone Pathway: Synthesis of HCV Polymerase Inhibitor GSK852A,HCV NS5B polymerase inhibitor GSK852A (1) was synthesized in only five steps from ethyl 4-fluorobenzoylacetate (3) in 46% overall yield. Key to the efficient route was the synthesis of the highly functionalized benzofuran core 15 from the β-keto ester in one pot and the efficient conversion of ester 6 to amide 19 via enamine lactone 22. Serendipitous events led to identification of the isolable enamine lactone intermediate 22. Single crystal X-ray diffraction and NMR studies supported the intramolecular hydrogen bond shown in enamine lactone 22. The hydrogen bond was considered an enabler in the proposed pathway from ester 6 to enamine lactone 22 and its rearrangement to amide 19. GSK852A (1) was obtained after reductive amination and mesylation with conditions amenable to the presence of the boronic acid moiety which was considered important for the desirable pharmacokinetics of 1. The overall yield of 46% in five steps was a significant improvement to the previous synthesis from the same β-keto ester in 5% yield over 13 steps.,10.1021/acs.joc.5b01598,2015-09-10,0.6684092273196752
Organic Letters,Total Synthesis of Oxazolomycin A,"The first total synthesis of oxazolomycin A, a structurally novel oxazole polyene γ-lactam/β-lactone antibiotic, is described. Key features include the stereocontrolled construction of the right-hand heterocyclic core by taking advantage of an In(III)-catalyzed Conia-ene type cyclization and the asymmetric synthesis of the left-hand segment starting with a Cinchona alkaloid-catalyzed cyclocondensation of an aldehyde with an acid chloride.",10.1021/ol202306d,2011-09-02,0.6683831709597162
Tetrahedron,One-pot three steps synthesis of cerpegin,,10.1016/s0040-4039(96)02014-x,1996-11-01,0.6683803439439525
Angewandte Chemie International Edition,Total Synthesis of Apicularen A through Transannular Pyran Formation,"A macrocyclization–transannulation strategy is the crux of an efficient total synthesis of the benzolactone enamide apicularen A (see scheme; Bn=benzyl). Key steps include a four-component coupling, a Stille cross-coupling to introduce the aromatic moiety, and the formation of the enamide from a hemiaminal. The size-selective macrolactonization of the ethoxyvinyl ester shown was followed by transannular etherification in excellent yield.",10.1002/anie.200460760,2004-11-02,0.6683550399510186
Organic Letters,"Enantioselective Total Synthesis of (−)-Vallesamidine Enabled by Asymmetric Hydrogenation and Aza-Wacker Cyclization to Construct the Core Spirocyclopentane-1,2′-indoline Structure","An enantioselective total synthesis of (-)-vallesamidine is described, integrating asymmetric hydrogenation with aza-Wacker cyclization to form the chiral spirocyclopentane-1,2'-indoline. Intramolecular Stetter reaction and alkylation are employed to construct a tetracyclic framework featuring a chiral quaternary carbon center. Schmidt rearrangement and intramolecular aldol condensation facilitate the formation of the D and E rings. This synthesis achieves (-)-vallesamidine in 14 steps in an overall yield of 4.2% from an exocyclic enone ester.",10.1021/acs.orglett.5c01615,2025-05-22,0.6683542557162051
Journal of the American Chemical Society,A Concise Total Synthesis of (−)-Maoecrystal Z,The first total synthesis of (-)-maoecrystal Z is described. The key steps of the synthesis include a diastereoselective Ti(III)-mediated reductive epoxide coupling reaction and a diastereoselective Sm(II)-mediated reductive cascade cyclization reaction. These transformations enabled the preparation of (-)-maoecrystal Z in only 12 steps from (-)-γ-cyclogeraniol.,10.1021/ja2073356,2011-08-30,0.6683328684605938
Tetrahedron,Novel heteroaromatic CH insertion of alkylidenecarbenes. A new entry to furopyridine synthesis,,10.1016/s0040-4039(98)01034-x,1998-07-01,0.6682888917632966
Journal of Organic Chemistry,A Concise Synthesis of <i>ent</i>-Cholesterol,ent-Cholesterol was synthesized in 16 steps from commercially available (S)-citronellol. The overall yield for the synthesis was 2.0%. This route is amenable to gram-scale preparation of ent-cholesterol. Isotopic incorporation near the end of the synthesis was achieved using labeled methyl iodide. This synthesis is the most practical to date and will make ent-cholesterol more readily available to use as a probe of the function and metabolism of cholesterol.,10.1021/jo702694g,2008-03-13,0.6682730979828025
Synthesis,Convergent First Total Synthesis of Melovinone: A Densely Substituted 3-Methoxy-4-quinolone Isolated from Melochia tomentosa L.,"The first total synthesis of melovinone, a nonrutaceous 3-methoxy-4-quinolone alkaloid isolated from Melochia tomentosa L., is reported. The target was acquired in a convergent fashion through the Suzuki–Miyaura cross-coupling reaction between an ortho-nitrobenzoic acid acetonyl ester derivative prepared from vanillin and potassium 5-phenyl-1-pentyltrifluoroborate, obtained from β-phenethyl bromide. The coupling was followed by a chemoselective reduction of the nitro group and a microwave-assisted and AcOH-promoted cyclization with rearrangement of the resulting acetonyl anthranilate. This afforded a pseudane intermediate, which was selectively methylated on the 3-OH. The synthetic pathway enabled to reach the objective in 11 steps and 18% overall yield. The 1H NMR spectra of the synthetic and natural product were in full agreement.",10.1055/s-0039-1690164,2019-08-12,0.6682376885815301
Angewandte Chemie International Edition,"A Unified Total Synthesis of the Actinoallolides, a Family of Potent Anti‐Trypanosomal Macrolides","Trypanosoma protozoan parasites are the causative agents of Chagas disease and sleeping sickness, two neglected tropical diseases where there is an urgent need for improved treatments and the evaluation of promising drug leads like the actinoallolides. Enabled by the highly stereocontrolled aldol reactions of three chiral ketone building blocks, an efficient first total synthesis of the potent anti-trypanosomal macrolide (+)-actinoallolide A has been achieved in 17 steps and 8 % overall yield. Our convergent route features an adventurous ring-closing metathesis to form the requisite trisubstituted (8E)-alkene in the 12-membered macrolactone, followed by the controlled installation of the labile transannular hemiacetal. Late-stage diversification then provides ready access to the congeneric (+)-actinoallolides B-E.",10.1002/anie.201914042,2019-11-19,0.6682307850122967
Journal of Organic Chemistry,"An Efficient, Stereoselective Synthesis of the Hydroxyethylene Dipeptide Isostere Core for the HIV Protease Inhibitor A-792611","A stereoselective synthesis of the hydroxyethylene dipeptide isostere 1 is described. The route employs a substrate-directed kinetic protonation of an alpha/gamma-substituted lactone to afford the desired stereochemistry. A method for converting the diastereomerically enriched intermediate lactone to the ring-open form with retention of stereochemistry is demonstrated. A novel procedure for utilizing N,N-dibromo-5,5-dimethylhydantoin in Hofmann rearrangements is disclosed. This route was used to prepare amino alcohol 1, the core portion of the HIV protease inhibitor A-792611, in 46% yield from phenylalanine-derived epoxide 2.",10.1021/jo060737s,2006-06-09,0.6682104085050103
Tetrahedron,"A new route to stereospecific synthesis of terpenoid 1,5-polyenes via isoprene cyclooligomers",,10.1016/s0040-4039(01)92719-4,1977-01-01,0.6682030362441013
Organic Process Research & Development,Synthetic Improvements in the Preparation of Clopidogrel,"Synthetic improvements in the preparation of clopidogrel are described. The synthesis was accomplished in four steps or one-pot in above 70% overall yield. The process featured PTC catalyzed alkaline hydrolysis of the key intermediate 2-(2-chlorophenyl)-2-(6,7-dihydrothieno[3,2- c ]pyridin-5(4 H )-yl)acetonitrile and highly effective kinetic resolution of racemic clopidogrel using l -camphorsulphonic acid in toluene and has been successfully used in a 50-kg pilot test.",10.1021/op700025d,2007-03-31,0.6681932764235913
Tetrahedron,A new route in the sequential total synthesis of compactin,,10.1016/s0040-4039(00)94509-x,1983-01-01,0.6681882865907164
Organic Letters,"A Concise, Selective Synthesis of the Polyketide Spacer Domain of a Potent Bryostatin Analogue","[reaction: see text] A concise, asymmetric synthesis of the polyketide spacer domain portion (C1-C13) of a highly potent bryostatin analogue was developed. The route utilizes asymmetric hydrogenation methodology to install the C3, C5, and C11 stereocenters, while a substrate directed syn reduction sets the C9 stereocenter. The spacer domain 1 is obtained in 10 steps with a 25% overall yield and is readily incorporated into the synthesis of 2.",10.1021/ol0272390,2003-01-09,0.6681705991373122
Organic Letters,Synthesis of (±)-7-Hydroxylycopodine,"A six step synthesis of (±)-7-hydroxylycopodine has been achieved in 5% overall yield. In the key step, a Prins cyclization of a bicyclic keto alkyne in 60% H(2)SO(4) forms a tricyclic dihydroxy amino ketone.",10.1021/ol200119h,2011-01-27,0.6681640403630449
Organic Process Research & Development,Investigation of Practical Routes for the Kilogram-Scale Production of <i>cis</i>-3-Methylamino-4-methylpiperidines,"Two routes for the synthesis of cis - N -protected-3-methylamino-4-methylpiperidine ( 3 ) were examined: a route hinging on the electrochemical oxidation of carbamate 1 to install a ketone at the 3 position of the piperidine followed by reductive amination (disconnection A), and a route involving the hydrogenation of an appropriately functionalized pyridine (disconnection B). While both routes to the desired compound were ultimately successful, the pyridine hydrogenation approach proved to be more amenable to kilogram-scale preparations due to the crystallinity and purity of intermediates in that route.",10.1021/op049808k,2005-01-01,0.6681533600390588
Journal of Organic Chemistry,Total Synthesis and Absolute Stereochemistry of Integric Acid,An efficient total synthesis of integric acid is described starting from the Wieland-Miescher ketone. Key steps involve a one-step orthogonal deprotection/protection strategy of a thioacetal/aldehyde and the selective oxidative cleavage of a prenyl group in the presence of two other unsaturated moieties. The synthesis of both C4' diastereoisomers of integric acid delivered unambiguous evidence for (S)-stereochemistry at the C4' position.,10.1021/jo901845r,2009-10-27,0.6681531258575738
Organic Letters,"Organocatalytic Asymmetric Total Synthesis of (<i>R</i>)-Rolipram and Formal Synthesis of (3<i>S</i>,4<i>R</i>)-Paroxetine","An efficient enantioselective total synthesis of (R)-rolipram and an efficient enantioselective formal synthesis of (3S,4R)-paroxetine has been achieved using the highly enantioselective Michael addition of malonate nucleophiles as key steps in both cases.",10.1021/ol800108u,2008-03-07,0.6681127645928501
Organic Process Research & Development,Practical Manufacturing Process for Baloxavir Marboxil: Effective Selection and Replacement of Protective Group toward Enhancement of Crystallization-Induced Diastereomer Transformation,"Baloxavir marboxil (BXM) is an influenza antiviral drug that exploits a cap-dependent endonuclease (CEN) inhibitor. The synthesis route used in the initial CMC development study had several problems hampering scale-up, such as poor stereochemical outcome which decreased the yield, usage of a corrosive reagent, and a cumbersome protocol for the key step. We addressed these problems to enable practical and operation-friendly manufacture of BXM at a larger production scale for early and successive CMC development. The new route includes the following steps: (1) a magnesium-mediated alkoxy displacement reaction to prepare an intermediate without loss of optical purity and (2) diastereoselective preparation of an intermediate via a dehydration condensation reaction with a crystallization-induced diastereomer transformation (CIDT) process. This facile route enabled scalable manufacturing to supply BXM.",10.1021/acs.oprd.3c00503,2024-04-04,0.6680788539060806
Organic Letters,Total Synthesis of (−)-Aplaminal,"The total synthesis and assignment of absolute configuration of (-)-aplaminal ( 1), a cytotoxic metabolite from a sea hare possessing a triazobicyclo[3.2.1]octane skeleton, has been achieved. The synthesis entailed condensation of a monoprotected diamine ( 3) with dimethyl 2-oxomalonate ( 4) to generate the imidazolidine core ( 2). Introduction of the third nitrogen via Mitsunobu activation and azide displacement, followed by reduction and lactam formation (AlMe 3), furnished (-)-aplaminal ( 1). Overall, the synthesis entailed 9 steps and proceeded in 19% overall yield.",10.1021/ol801794f,2008-08-28,0.6680731492531897
Journal of the American Chemical Society,"Development of a Modular Synthetic Route to (+)-Pleuromutilin, (+)-12-<i>epi</i>-Mutilins, and Related Structures","We describe the development of an enantioselective synthetic route to (+)-pleuromutilin (1), (+)-12-epi-mutilin, and related derivatives. A key hydrindanone was prepared in three steps and 48% overall yield from cyclohex-2-en-1-one. 1,4-Hydrocyanation provided a nitrile (53%, or 85% based on recovered starting material) that was converted to the eneimide 57 in 80% yield by the 1,2-addition of methyllithium to the nitrile function, cyclization, and in situ acylation with di-tert-butyldicarbonate. The eneimide 57 was employed in a 2-fold neopentylic coupling reaction with an organolithium reagent derived from the alkyl iodides (R)- or (S)-30, which contain the C11-C13 atoms of the target, to provide diastereomeric diketones in 60% or 48% yield (for coupling with (R)- or (S)-30, respectively). The diketone derived from (S)-30 contains the (S)-C12 stereochemistry found in pleuromutilin and was elaborated to an alkynylaldehyde. Nickel-catalyzed reductive cyclization of this alkynylaldehyde, to construct the eight-membered ring of the target, unexpectedly provided a cyclopentene (67%), which arises from participation of the C12-α-olefin in the transformation. The diketone derived from the enantiomeric C12-fragment (R)-30 underwent reductive cyclization to provide the desired product in 60% yield. This was elaborated to 12-epi-mutilin by a four-step sequence (39% overall). Installation of the glycolic acid residue followed by C12 epimerization (Berner et al. Monatsh. Chem. 1986, 117, 1073) generated (+)-pleuromutilin (1). (+)-12-epi-Pleuromutilin and (+)-11,12-di-epi-pleuromutilin were prepared by related sequences. This work establishes a convergent entry to the pleuromutilins and provides a foundation for the production of novel antibiotics to treat drug-resistant and Gram-negative infections.",10.1021/jacs.7b09869,2017-10-19,0.6680666556588136
Organic Letters,Synthesis of Rumphellaone A and Hushinone by a Gold-Catalyzed [2 + 2] Cycloaddition,"The enantioselective total synthesis of rumphellaone A has been accomplished in 12 steps via a diastereoselective gold(I)-catalyzed [2 + 2] macrocyclization of a 1,10-enyne as the key step to build the cyclobutene moiety. This concise approach has also led to the total synthesis of husinone.",10.1021/acs.orglett.6b00473,2016-03-14,0.6680374601999486
Organic Letters,Enantioselective Total Synthesis of Peloruside A:  A Potent Microtubule Stabilizer,"An enantioselective total synthesis of (+)-peloruside A (1) is described. Peloruside A (1) is a potent microtubule stabilizer with significant clinical potential. The synthesis is convergent and involves the assembly of C1-C10 segment 2 and C11-C24 segment 3 by a novel aldol protocol followed by Yamaguchi macrolactonization of the resulting seco-acid, selective methylation of hemi-ketal and removal of the protecting groups to peloruside A.",10.1021/ol703091b,2008-02-05,0.668031279136157
Organic Letters,A Concise Enantioselective Entry to the Synthesis of Deoxy-azasugars,"[reaction: see text] A concise enantioselective preparation of oxazolidinylpiperidine 4, a key intermediate in the synthesis of glycosidase inhibitors such as 1-deoxymannojirimycin or 1-deoxygalactostatin, has been developed. Sharpless catalytic asymmetric epoxidation of (E)-2,4-pentadienol followed by treatment with allyl isocyanate afforded epoxy carbamate 8. Regioselective intramolecular ring opening promoted by sodium bis(trimethylsilyl)amide and ring-closing metathesis provided the bicyclic intermediate 4 in high enantiomeric purity. The four-step sequence takes place in 51% overall yield.",10.1021/ol991280u,1999-12-17,0.6680284713236277
Journal of Organic Chemistry,"Diastereoselective Synthesis of a <i>cis</i>-1,3-Disubstituted Cyclobutane Carboxylic Acid Scaffold for TAK-828F, a Potent Retinoic Acid Receptor-Related Orphan Receptor (ROR)-γt Inverse Agonist","High Resolution Image Download MS PowerPoint Slide A scalable synthesis of the cis -1,3-disubstituted cyclobutane carboxylic acid scaffold of TAK-828F ( 1 ) has been developed, featuring the diastereoselective reduction of a cyclobutylidene Meldrum’s acid derivative with NaBH 4 . Controlling acidic impurities was crucial for improving the diastereomeric ratio by recrystallization. Furthermore, reaction optimization and the streamlining of several steps established a scalable synthetic method free from column chromatography purification with an overall yield improved from 23 to 39%.",10.1021/acs.joc.1c00970,2021-08-06,0.6680171671598459
Journal of Organic Chemistry,Practical Asymmetric Synthesis of an Endothelin Receptor Antagonist,"An efficient, practical, asymmetric synthesis of the endothelin receptor antagonist 1 is reported. The key pyridine-fused cyclopentane ring bearing three consecutive chiral centers was constructed by first an auxiliary induced asymmetric conjugate addition of the bottom aryllithium from 19 to an unsaturated ester 21 in high diastereoselectivity. After a highly diastereoselective addition of the top aryl Grignard reagent to the aldehyde 22, the alcohol product then underwent a stereospecific intramolecular alkylation of the ester enolate by the phosphate of the alcohol, resulting in the desired trans−trans relative stereochemistry on the cyclopentane ring. The two key chiral centers that set the chirality of the molecule were both induced from cis -1-amino-2-indanol-derived chiral auxiliaries, one in the conjugate addition reaction, the other in setting the chiral center of the bottom side chain via chiral alkylation of an enolate. Oxidation of the primary alcohol to the carboxylic acid in the bottom side chain was carried out with the newly developed TEMPO/bleach-catalyzed oxidation by sodium chlorite (NaClO 2 ) or chromium oxide catalyzed oxidation by periodic acid. The overall process has been run successfully to make multikilograms of the drug in high purity.",10.1021/jo991292t,1999-12-01,0.6680057590834275
Organic Letters,Total Synthesis of (−)-Brevisin: A Concise Synthesis of a New Marine Polycyclic Ether,The first and highly efficient total synthesis of (-)-brevisin has been achieved. The title compound was synthesized in only 29 steps (longest linear sequence) from commercially available starting materials. The synthesis provided over 70 mg of a marine polycyclic ether compound.,10.1021/ol102925d,2011-01-19,0.6679808952127897
Tetrahedron,"Ring contraction of 4-oxo-1,3-dioxanes a new route to β-lactones",,10.1016/s0040-4039(01)97733-0,1969-01-01,0.6679712799056898
Journal of the American Chemical Society,Synthesis of Bistramide A,"We have developed an efficient and highly stereocontrolled synthesis of bistramide A, a selective activator of protein kinase C isotype delta. Our synthetic strategy featured a novel bidirectional approach for spiroketal construction based on the ring-opening/cross-metathesis sequence employing a highly strained cyclopropenone acetal. The synthesis afforded the final target with the longest linear sequence of 15 steps and provided unambiguous structural determination of bistramide A, including assignment of the previously unknown C(37) stereochemistry.",10.1021/ja046588h,2004-07-20,0.6679676194431649
Organic Process Research & Development,Process Development of a Potent Neuroprotector Agent: Collismycin A,"An efficient synthetic process for the natural product of marine origin, collismycin type A, a potent neuroprotector agent, has been developed. This new synthetic route avoids chromatographic steps, implies an improvement cost, and provides easy access to large scale.",10.1021/op3003129,2012-12-21,0.6679533523879875
Synthesis,Studies toward the Total Synthesis of Carolacton,"An efficient synthesis of the C1–C19 segment of carolacton is described, starting from d -ribose, (–)-β-citronellene and a homopropargylic alcohol, and which employs a Nozaki–Hiyama–Kishi (NHK) coupling as the key step. Other important steps are cross-metathesis and Evans aldol reactions.",10.1055/s-0032-1317700,2012-12-17,0.6679376924524635
Journal of Organic Chemistry,Total Synthesis of (+)-Ambruticin S: Probing the Pharmacophoric Subunit,"An enantioselective synthesis of the antifungal natural product (+)-ambruticin S has been accomplished starting with the readily available methyl alpha-d-glucopyranoside, (R)-Roche ester, and (S)-glycidol as chirons, which encompassed seven of the 10 stereogenic centers of the target molecule. The remaining three centers were set by a highly diastereoselective, asymmetric cyclopropanation employing a chiral, nonracemic phosphonamide reagent. Our strategy for the construction of the dihydropyran subunit involved a highly syn-selective Lewis acid catalyzed 6-endo-trig cyclization. Other key steps in the synthesis featured an epoxide opening with a dithiane anion, two efficient phosphonamide-anion based olefinations, and a late-stage C-glycosylation.",10.1021/jo100956v,2010-07-20,0.6679162594259621
Journal of Organic Chemistry,Studies toward the Asymmetric Synthesis of the Right Part of the Mycalamides,"Described herein is the asymmetric synthesis of a functionalized, trioxadecalin unit that comprises the right-hand part of the mycalamides and related natural products. The synthetic route involves a 16-step sequence that accomplishes the formation of two heterocyclic rings and the generation of five stereocenters. The synthesis commenced with a C2-symmetric starting material, diethyl D-tartrate, and took advantage of a relay of diastereoselective reactions to extend this four-carbon chain and introduce new chiral centers. Subsequent electrophile-mediated cyclization afforded the desired pyran ring, which was then transformed into the desired, functionalized trioxadecalin skeleton.",10.1021/jo0615145,2006-12-23,0.6678538747875075
Journal of Organic Chemistry,Enantioselective Total Synthesis of the Potent Anti-inflammatory (+)-Myrrhanol A,"The first total synthesis of potent anti-inflammatory polypodanes (+)-myrrhanol A (1), (+)-myrrhanone A (2), (+)-myrrhanone B (3), and (+)-myrrhanol B (4) has been achieved. Key steps in our convergent, highly stereocontrolled route are a Ti(III)-mediated radical cyclization of a chiral monoepoxide to furnish a bicyclic synthon that combines stereospecifically with an acyclic vinyl iodide via an intermolecular B-alkyl Suzuki-Miyaura cross-coupling.",10.1021/jo901011m,2009-07-06,0.6678299705176416
Tetrahedron,Efficient synthesis of a ryanodine binding inhibitor verticilide using two practical approaches,,10.1016/j.tetlet.2020.151699,2020-02-14,0.6678274170653579
Organic Process Research & Development,"Process Optimization for the Large-Scale Preparation of (2<i>S</i>,3<i>aR</i>,7<i>aS</i>)-<i>tert</i>-Butyl Hexahydro-2,5-methanopyrrolo[3,2-<i>c</i>]pyridine-1(4<i>H</i>)-carboxylate, an Intermediate for Nicotinic Acetylcholine Receptor Agonists","An optimized large-scale synthesis of (2 S,3 aR,7 aS )- tert -butyl hexahydro-2,5-methanopyrrolo[3,2- c ]pyridine-1(4 H )-carboxylate ( 1A ), an important intermediate for nicotinic acetylcholine receptor agonists, is described. The key feature of the synthesis involves three transformations in a one-pot process, including debenzylation and ring hydrogenation of two fused bicyclic rings. Multihundred gram quantities of 1A were prepared.",10.1021/acs.oprd.8b00208,2018-08-28,0.6678095663744394
Organic Process Research & Development,"Development of a Scalable, Racemic First-Generation Route for CXCR7 Antagonist ACT-1004-1239 via <i>cis</i>-to-<i>trans</i> Epimerization and Subsequent Separation of Enantiomers","The high structural complexity of CXCR7 antagonist ACT-1004-1239 turned the development of a scalable route into a formidable challenge. The presence of two stereocenters, the intermediacy of highly polar or fluorinated heterocyclic building blocks, and the extremely low solubility of the API were just three of the factors that contributed to this challenge. Given the high time pressure on the project, a racemic route was developed with priority in less than 12 months. The key to success was the synthesis of racemic N -Boc-3-methyl 4-aminopiperidine-3-carboxylate ( cis: trans 2:1) and its isolation in high chemical purity as the crystalline TFA salt. After amide coupling with 5-(2,4-difluorophenyl)isoxazole-3-carboxylic acid, the 3-position of the piperidine ring was fully epimerized to the more stable trans -isomer by using NaOMe. At this stage, the trans enantiomers were separated by liquid chromatography on a chiral stationary phase. The desired 3 S,4 S -enantiomer was recovered in excellent yield (48%, compared with theoretical 50%) and purity (e.r. 99.8:0.2). After a final sequence of saponification, amide coupling, Boc deprotection and reductive amination with cyclopropanecarboxaldehyde, the API was isolated as a white solid with high purity. Over 500 g of API was produced in-house for preclinical activities with this racemic route, which was also used to produce 5.5 kg of GMP material at an external manufacturing partner for Phase 1 clinical studies.",10.1021/acs.oprd.3c00445,2024-01-22,0.667760816634143
Synlett,"Short Synthesis of the Antidiabetic Octaketide Ethyl 2-(2,3,4-Trimethoxy-6-octanoylphenyl)acetate","A facile and practical approach for the synthesis of ethyl 2-(2,3,4-trimethoxy-6-octanoylphenyl)acetate, an antidiabetic octaketide analogue of cytosporone B, is described. Unlike known approaches for the synthesis of cytosporones and their analogues, the key step of the developed route is a Friedel–Crafts alkylation of 1-(3,4,5-trimethoxyphenyl)octan-1-one with ethyl chloro(methylthio)acetate, followed by desulfurization.",10.1055/s-0036-1592062,2017-11-28,0.6677434865303734
Synthesis,Exploratory Process Development of Pexidartinib through the Tandem Tsuji–Trost Reaction and Heck Coupling,A novel synthetic route to CSF1R inhibitor pexidartinib was designed and demonstrated. Crucial to the successful synthesis is a tandem Tsuji–Trost reaction and Heck coupling in combination with palladium and silver catalysis. The final product was obtained via five steps in 49% yield with purity as high as 99.2%. The cheap and available materials and reagents and easy operations for workup and purification make this route more practical.,10.1055/s-0037-1612421,2019-04-01,0.6677288686716636
Organic Letters,"Asymmetric Synthesis of (<i>+</i>)-(<i>S</i>,<i>S</i>)-Reboxetine via a New (<i>S</i>)-2-(Hydroxymethyl)morpholine Preparation","(S,S)-Reboxetine was synthesized stereospecifically in 30% overall yield and 99% ee in eight steps. Key steps were selective oxidation of an N-protected hydroxymethylmorpholine and aryl-chromium-mediated aromatic nucleophilic substitution. [structure: see text]",10.1021/ol050059g,2005-01-25,0.6677023139234421
Tetrahedron,A concise formal synthesis of bufogargarizin B,A concise and scalable formal synthesis of bufogargarizin B has been achieved by completing the synthesis of the advanced [5–7–6–5] tetracyclic intermediate II in 8 steps with 36 % overall yield from commercially available estrone 8 . Key features of the synthesis include stereoselective reduction of the carbonyl group and an oxidative cleavage/transannular aldol cascade reaction to rapidly construct the rearranged A/B ring system and three stereogenic centers. This study presents a new synthetic approach to the unique rearranged framework of bufogargarizin B and related steroids.,10.1016/j.tetlet.2025.155627,2025-04-28,0.6676306729285513
Organic Letters,A Concise Total Synthesis of Melithiazole C,A short and convergent synthesis of the myxobacterial antibiotic melithiazole C is described featuring a highly E-selective cross-metathesis as the key step.,10.1021/ol701459j,2007-07-18,0.66762149213621
Tetrahedron,Synthesis of (±)-Pentalenene,"A short, formal synthesis is reported for pentalenene. The key steps are copper-catalyzed 1,4-addition of isobutylmagnesium bromide to a cyclooctenone derivative, enolate alkylation with the thiocarbene complex [(η5-C5H5)(CO)2Fe=CHSPh]+ PF6−, and cyclopentane ring formation by means of intramolecular C-H insertion, leading to a late intermediate in a previously reported synthesis of pentalene.",10.1016/s0040-4039(00)93547-0,1991-10-01,0.667614905030067
Synlett,A Palladium-Catalysed Urea Arylation Route to a CRF1 Receptor Antagonist,"A new synthetic approach to a potent CRF antagonist, GW808990 (NBI35583), is reported. The route hinges on the palladium-catalysed intramolecular arylation of a urea with 2-chloro­pyridine. Spontaneous piperazine ring closure means that a high-yielding bisannulation reaction is the final step.",10.1055/s-2006-950276,2006-10-01,0.6675799220685394
Tetrahedron,A new enantiospecific route toward monocarbocyclic terpenoids: Synthesis of (−)- caparrapi oxide,,10.1016/s0040-4039(98)02119-4,1998-12-01,0.6675736417508966
Angewandte Chemie International Edition,A Rapid Stereocontrolled Entry to the ABCD Tetracyclic Core of Neotuberostemonine,"Four out of the five rings of the alkaloid neotuberostemonine (1) are present in the advanced precursor 2. The tetracyclic compound 2 has now been prepared in a short, linear route via lactone acid 3. A key step in the synthesis was the cuprate-mediated SN2′ ring-opening desymmetrization of the C2-symmetric bislactone 4.",10.1002/anie.200250507,2003-04-10,0.6675573161289787
Journal of Organic Chemistry,"A Facile and Efficient Synthesis of 3,3-Dimethyl Isopropylidene Proline From (+)-3-Carene","A highly efficient and practical route to 3,4-isopropylidene proline I, starting from (+)-3-carene, was developed. The three continuous stereocenters were constructed using the inherent chirality of the starting natural product 2. The overall yield for the 12-step synthesis is 34%. The optimized sequence leading to 1 has been successfully applied on a multigram scale, thereby establishing the practicality of this route.",10.1021/jo9022759,2010-01-28,0.66754841430505
Organic Process Research & Development,"Early Process Development of PF-07054894, a Squaramide-Based Antagonist of C–C Chemokine Receptor Type 6 (CCR6)","The original synthesis of a CCR6 antagonist and subsequent enablement for kilogram manufacture is presented. Highlighted improvements made in the preparation for the scale-up campaign include (1) a refined route to access a key iodopyrazole which previously suffered from low yield due to poor regioselectivity, (2) optimization of a sulfinimine addition reaction to form a sterically congested amine with high stereocontrol, (3) implementation of a route to an aminopyridine fragment, and (4) efficient construction of the target molecule by sequential substitution of diethyl squarate with two elaborated amines. These enablement efforts have resulted in the successful preparation of >7 kg of crystalline API to perform early toxicological studies and initiate Phase 1 clinical trials.",10.1021/acs.oprd.3c00451,2024-01-30,0.6675305518562719
Angewandte Chemie International Edition,Access to Guaianolides: Highly Efficient Stereocontrolled Total Synthesis of (±)‐Geigerin,"Geiger counter: The first total synthesis of geigerin (3), a member of the guaian-8,12-olides, has been achieved in eight regio- and stereocontrolled steps from the tropylium cation. En route, the guaian-6,12-olide 2 is formed in two steps from the hydroazulenone 1, a versatile intermediate.",10.1002/anie.200702031,2007-08-03,0.6674668680680965
Organic Process Research & Development,"Synthetic Process Development of Antitumor Agent KT6587, an Indolocarbazole Alkaloid K252a Derivative","A facile and large-scale preparation process of an antitumor agent KT6587 ( 2 ), derived from an indolocarbazole alkaloid K252a ( 1 ), has been developed. The new synthetic process requires four steps: (i) selective N -silylation of the amide group of 1 with tert -butyldimethylsilyl chloride, (ii) methylation of the hydroxy group, (iii) deprotection under aqueous acidic conditions to afford 3, and (iv) reduction of the methoxycarbonyl group to obtain 2 . The key strategic improvement is to obtain fine quality of the intermediate 3 in a reasonable yield with reproducibility. This new process improves the overall yield from 33% to 70% without tedious chromatographic separations and hazardous conditions. Multikilogram quantities of KT6587 ( 2 ) for early clinical evaluation have been obtained by this method.",10.1021/op980087x,1999-02-26,0.6674320565027838
Journal of Organic Chemistry,Total Synthesis of (−)-Graminin A Based on Asymmetric Cyclization Carbonylation of Propargyl Acetate,"The first total synthesis of (-)-graminin A is described. Key features of our synthetic approach involve a palladium-catalyzed asymmetric cyclization carbonylation of prochiral propargylic acetate, conversion of the orthoester product into methyl 4-oxo-3-furancarboxylate, and copper complex-mediated aldol condensation of (+)-gregatin B bearing a diene moiety. A new synthesis of (+)-gregatin B and the first synthesis of (-)-graminin A were achieved.",10.1021/acs.joc.9b02886,2019-12-02,0.6674261421111255
Tetrahedron,WITHDRAWN: A short and efficient synthesis of the selective H4 receptor agonist 4-methylhistamine,,10.1016/j.tetlet.2007.09.055,2007-09-01,0.6673949902704082
Synlett,Oxazole Synthesis from Isocyanides,A new synthetic path toward oxazoles starting from isocyanides is presented. This two-step oxazole preparation involves a bromination–cyclization followed by a Suzuki cross-coupling.,10.1055/s-0031-1290939,2012-05-14,0.6673865968436221
Organic Letters,Synthesis of Rigid Multivalent Scaffolds Based on Adamantane,"An efficient route to novel 1,3,5,7-tetrasubstituted derivatives of adamantane is described. This route starts from adamantane and gives the tetrafunctionalized derivative 9 in eight steps with an overall yield of 23%. These tetrahedrally shaped molecules possess three identical arms terminated by an activated carboxylic acid derivative and a protected amino function in the 1-position. We propose these tetravalent cage compounds such as 9 as scaffolds for the assembly of ligand/marker conjugates for studies of multivalent ligand receptor interactions. [reaction: see text]",10.1021/ol048055j,2004-10-29,0.6673492923231957
Organic Process Research & Development,"Synthesis of Nirmatrelvir: Development of an Efficient, Scalable Process to Generate the Western Fragment","Nirmatrelvir ( 1 ), a novel and specific inhibitor of the SARS-CoV-2 3C-like protease, was developed by Pfizer scientists in mid 2020. Efforts to develop a scalable process to manufacture nirmatrelvir were undertaken with a great sense of urgency, as there were no effective treatments available for the worldwide patient population at that time. We used a convergent approach to generate this molecule. The first two steps used to generate the western fragment of nirmatrelvir from l - tert -leucine, ethyl trifluoroacetate, and a [3.1.0] bicyclic proline derivative are described here. This is the first of a series of four papers describing the commercial process of the development of nirmatrelvir.",10.1021/acs.oprd.3c00249,2023-11-25,0.667338642743485
Synthesis,Organocatalytic Approach to the Enantioselective Total Synthesis of (+)-Serinolamides A and B and (+)-Lacosamide,"Abstract A short and highly efficient enantioselective synthesis of (+)-serinolamide A, B and (+)-lacosamide from 3-methoxypropanal using l-proline-catalyzed α-amination, Grubbs metathesis, and acid-amine coupling as key steps is reported.",10.1055/a-2222-3822,2023-12-04,0.6673347717855609
Organic Process Research & Development,"Development of a Multigram Asymmetric Synthesis of 2-(<i>R</i>)-2-(4,7,10-Tris <i>tert</i>-Butylcarboxymethyl-1,4,7,10-tetraazacyclododec-1-yl)-pentanedioic Acid, 1-<i>tert</i>-Butyl Ester, (<i>R</i>)-<i>tert</i>-Bu<sub>4</sub>-DOTAGA","A process for the multigram asymmetric synthesis of the chiral tetraazamacrocycle 2-( R )-2-(4,7,10-tris tert -butylcarboxymethyl-1,4,7,10-tetraazacyclododec-1-yl)-pentanedioic acid, 1- tert -butyl ester (( R )- tert -Bu 4 -DOTAGA, 4 ) has been devised and demonstrated. The nine-step synthesis features an improved synthesis of 2-( S )-5-oxotetrahydrofuran-2-carboxylic acid, tert -butyl ester 8, the precursor to the novel alkylating agent ( S )-5-benzyl 1- tert -butyl 2-(methylsulfonyloxy)pentanedioate 12, which was used to introduce an orthogonally protected chiral glutarate arm to the 1,4,7,10-tetraazacyclododecane (cyclen) nucleus in high optical purity. Cyclen derivative ( R )- t -Bu 4 -DOTAGA, 4, a key intermediate for the manufacture of a magnetic resonance imaging (MRI) candidate, was produced with high chemical (≥95%) and optical (ee ≥ 97%) purity. The process developed was successfully applied to the kilogram-scale cGMP synthesis of ( R )- t -Bu 4 -DOTAGA.",10.1021/op8002932,2009-03-20,0.6673143600661817
Journal of the American Chemical Society,Total Syntheses of (+)-Himbacine and (+)-Himbeline,"Himbacine (1), a complex piperidine alkaloid isolated from the bark of Australian magnolias, is a promising lead in Alzheimer's disease research due to its potent muscarinic receptor antagonist property. We have described here a highly efficient synthetic strategy that resulted in the total synthesis of himbacine (1) in about 10% overall yield and isohimbacine (1a), an unnatural isomer of himbacine, in 18% overall yield. The total synthesis of himbacine was initially approached using an intramolecular Diels-Alder reaction as the key step to generate intermediate 5 followed by a [3 + 2] cycloaddition with nitrone 4 to produce the isoxazolidine derivative 3. Methylation followed by catalytic reduction of 3 gave 12'-hydroxyhimbacine (20), which, upon dehydration, gave isohimbacine (1a) as the sole product. In an alternative approach, an all-encompassing intramolecular Diels-Alder reaction of an appropriately substituted tetraene derivative 31, which bears the entire latent carbon framework and functional group substitution of himbacine, gave the desired advanced tricyclic intermediate 33, which was readily converted to (+)-himbeline (2) and (+)-himbacine (1).",10.1021/ja00141a036,1995-09-01,0.6672764773901019
Journal of Organic Chemistry,"Total Synthesis of an Immunosuppressive Glycolipid, (<i>2S,3S,4R</i>)-1-<i>O</i>- (α-<scp>d</scp>-Galactosyl)-2- tetracosanoylamino-1,3,4-nonanetriol","[reaction: see text] A practical and efficient total synthesis of (2S,3S,4R)-1-O-(alpha-d-galactosyl)-2-tetracosanoylamino-1,3,4-nonanetriol, OCH 1b, a potential therapeutic candidate for Th1-mediated autoimmune diseases, is described. The synthesis incorporates direct alkylation onto epoxide 5 and stereospecific halide ion catalyzed alpha-glycosidation reaction. A key intermediate 10 was obtained in only eight steps and 37% overall yield from commercially available d-arabitol 2, and the total synthesis of 1b was accomplished in 12 steps and 19% overall yield. This method will enable the synthesis of a variety of phytosphingolipids, especially that with the shorter sphingosine side chain than 1a, in a highly stereoselective manner.",10.1021/jo048151y,2005-02-16,0.6672592357508037
Organic Letters,Stereoselective Total Synthesis of (±)-5-<i>epi</i>-Cyanthiwigin I via an Intramolecular Pauson–Khand Reaction as the Key Step,A convenient approach to the construction of the 5-6-7 tricarbocyclic fused core structure of cyanthiwigins via a Co-mediated Pauson-Khand reaction as a key step has been developed. The cyathane core intermediate obtained by this strategy was used in the concise synthesis of (±)-5- epi-cyanthiwigin I. The developed chemistry paves the way for the total synthesis of structurally diverse cyanthiwigins.,10.1021/acs.orglett.8b00903,2018-05-09,0.6672530390150406
Journal of Organic Chemistry,Total Synthesis of (−)-Chanoclavine I and an Oxygen-Substituted Ergoline Derivative,An efficient and direct route to ergot alkaloid (-)-chanoclavine I (3) is described using the inexpensive compound (2R)-(+)-phenyloxirane (15) as a chiral pool in 13 steps with 17% overall yield. Key features of the synthesis include a palladium-catalyzed intramolecular aminoalkynylation of terminal olefin and a rhodium-catalyzed intramolecular [3 + 2] annulation. An oxygen-substituted ergoline derivative (-)-25 was also achieved by using the same strategy.,10.1021/acs.joc.7b00573,2017-07-17,0.6672184119941805
Synthesis,A Simple Synthesis of the Novel Antihistaminic Drug Olopatadine Hydrochloride,A new alternative route for the synthesis of olopatadine is described. The present strategy involves a Lewis acid mediated ring opening of a cyclic ether to introduce 3-(dimethylamino)propylidene group as the side chain.,10.1055/s-0033-1340008,2013-10-23,0.667216547512315
Journal of Organic Chemistry,"Synthetic Studies toward the Partial Ergot Alkaloid LY228729, a Potent 5HT<sub>1A</sub> Receptor Agonist","Synthetic studies on LY228729 ( 3 ) afforded two innovative approaches for the construction of this class of partial ergoline 5HT 1a receptor agonists. The first synthesis is based upon a diastereoselective epoxidation of racemic olefin 5, followed by ring opening and covalent resolution to furnish the key amino alcohol 8 . Aziridination of amino alcohol 8, with subsequent tandem hydrogenolysis of the benzylic aziridine and auxiliary bonds, provided access to the optically active primary amine 13 . A novel catalytic carboxamidation reaction installed the requisite side chain. Alternatively, the chiral pool was drawn upon for the single stereogenic center by virtue of l -tryptophan, albeit by a more circuitous route than expected. l -Tryptophan was differentially protected and reduced to the indoline diastereomers 26a,b which were separated by fractional crystallization. The two indoline diastereoisomers were independently cyclized by a Friedel−Crafts protocol, which under thermodynamic control afforded enantiomeric ketones 30a . The ketone was deoxygenated with a two-step reduction protocol to intersect the initial route and complete the second total synthesis. The two routes offer complementary access to this exciting class of partial ergot alkaloids.",10.1021/jo971256z,1997-12-01,0.667199887308799
Organic Letters,<i>De Novo</i> Asymmetric Synthesis of (+)-Monanchorin,"A de novo asymmetric total synthesis of the guanidine alkaloid natural product (+)-monanchorin has been achieved in nine steps from the commodity chemicals furan and caproic acid. The asymmetry of the route was introduced by a Noyori reduction of an acylfuran. In addition, this route relies upon an Achmatowicz rearrangement, a diastereoselective palladium catalyzed glycosylation, reductive amination, and an acid catalyzed bicyclic guanidine mixed acetal formation.",10.1021/acs.orglett.5b02651,2015-10-13,0.6671978185085172
European Journal of Organic Chemistry,Flexible Synthesis and Herbicidal Activity of Fully Substituted 3‐Hydroxypyrazoles,"Abstract The synthesis and herbicidal efficacy of a novel library of fully substituted 3‐hydroxypyrazoles is reported. An efficient, divergent approach to introduce phenyl, phenoxy, phenylsulfanyl, anilino and benzyl substituents in the 4‐position of the pyrazole, alongside a flexible synthesis of N1 ‐alkyl analogues is described via final step diversification of key intermediates. Herbicidal screening of the prepared compounds against key weed species identified the lead compound 2‐[4‐(2,4‐difluorophenoxy)‐1,5‐dimethyl‐pyrazol‐3‐yl]oxy‐5‐fluoropyrimidine, which was prepared on a multi‐gram scale using an optimised synthetic route.",10.1002/ejoc.202100468,2021-07-27,0.6671476709560648
Organic Process Research & Development,"Development of a Practical and Scalable Synthesis of the Side Chain for ASP9726, a Successor of Micafungin","Here, we describe a practical and scalable synthesis of 1, which is a useful side chain of ASP9726 ( 2 ), a successor of Micafungin. For large-scale synthesis of 1, reaction conditions were optimized to control impurities and increase yield. In particular, we utilized a high-yield thiadiazole ring formation to prepare thiadiazole 12, a step which was improved by optimization of reaction conditions and isolation method. Further, the number of steps was reduced from 10 to 9, and hazardous reactions were also avoided. Consequently, this process was scaled to produce 21.7 kg of 1 with overall yield improvement from 36.7% to 56.6%.",10.1021/op400211t,2013-09-20,0.667102211125709
Angewandte Chemie International Edition,A Convergent Route for the Total Synthesis of the Eleuthesides,"A ring expansion/ring contraction sequence is one of the key steps in the stereoselective synthesis of the tricyclic eleutheside skeleton 2 from α-phellandrene 1. Eleuthesides are natural products that are isolated from different marine sources, and several of these compounds display taxol-like anticancer activity.",10.1002/(sici)1521-3773(19980202)37:1/2<185::aid-anie185>3.0.co;2-l,1998-02-02,0.6671008268960967
Organic Letters,Total Synthesis of (±)-Brussonol and (±)-Komaroviquinone via a Regioselective Cross-Electrophile Coupling of Aryl Bromides and Epoxides,"The short and stereoselective syntheses of diterpenes (±)-brussonol and (±)-komaroviquinone, via a Ni-catalyzed epoxide ring-opening approach in the presence of aryl halides, is described. Key steps involve the effective preparation of a challenging hemiacetal intermediate in a single operation, followed by a highly efficient BF 3 ·OEt 2 -catalyzed Friedel–Craft alkylation, to construct the tricyclic skeleton of these diterpenes. The synthetic approach might offer a unified route for the synthesis of several natural products containing icetexane motifs.",10.1021/acs.orglett.9b02221,2019-07-25,0.6670957564755718
Tetrahedron,An enantioselective synthesis of a key intermediate to thienamycin by chemicoenzymatic approach,,10.1016/0040-4039(88)85334-6,1988-01-01,0.6670876513356548
Tetrahedron,A synthesis of inside-inside bicyclics. A one step synthesis of [10] paracyclophanes.,,10.1016/s0040-4039(01)93259-9,1977-01-01,0.6670550521369139
Journal of Organic Chemistry,"Discovery and Development of Metal-Catalyzed Coupling Reactions in the Synthesis of Dasabuvir, an HCV-Polymerase Inhibitor","Dasabuvir (1) is an HCV polymerase inhibitor which has been developed as a part of a three-component direct-acting antiviral combination therapy. During the course of the development of the synthetic route, two novel coupling reactions were developed. First, the copper-catalyzed coupling of uracil with aryl iodides, employing picolinamide 16 as the ligand, was discovered. Later, the palladium-catalyzed sulfonamidation of aryl nonaflate 33 was developed, promoted by electron-rich palladium complexes, including the novel phosphine ligand, VincePhos (50). This made possible a convergent, highly efficient synthesis of dasabuvir that significantly reduced the mutagenic impurity burden of the process.",10.1021/acs.joc.8b02690,2019-01-10,0.6670478649856362
Synthesis,"An Improved Synthesis of (<i>E</i>)-2-(4-Hydroxy-3-methyl-2-butenyl)-1<i>H</i>-isoindole-1,3(2<i>H</i>)-dione: A Key<i>trans</i>-Zeatin Intermediate",,10.1055/s-1983-30396,1983-01-01,0.6670160425719849
Organic Process Research & Development,Industrial Scale-Up of Enantioselective Hydrogenation for the Asymmetric Synthesis of Rivastigmine,"Two efficient processes for the synthesis of rivastigmine, one of the most potent drugs for the treatment of mild-to-moderate dementia of the type presenting in Alzheimer’s disease, has been developed. Of particular note is the processes used for the asymmetric hydrogenation by applying the highly efficient chiral spiro catalyst, Ir-SpiroPAP. The first route was easy to scale up in industry and provided the commercial intermediate ( S )-3-(1-dimethylaminoethyl)phenol, 6, which is suitable for the manufacture of rivastigmine in active pharmaceutical ingredient (API) demand. The second route was convenient for operation and purification and completed the synthesis of rivastigmine ( 1 ) in four steps and 84% overall yield.",10.1021/op3003147,2013-01-08,0.6670031602714499
Synlett,Synthesis of a Benzoannelated Spheriphane (Globular Cyclophane) on the Way to Potential Precursors of C<sub>60</sub>-Fullerene,"A viable route to the novel globular cyclophane 2, a C48H36-spheriphane, is presented as a result of our research aimed at the synthesis of the hypothetical deciphenyl 3, a C60H36-spheri­phane, which has been envisaged as a potential precursor to C60-fullerene. Several syntheses of the key intermediate of the route to 2, viz. septiphenyl 13 (C48H42), a sterically crowded 1,3,5-tris(ortho-biphenylyl)benzene derivative, are described. These include threefold Heck coupling and related threefold Pd(0)-catalyzed C-C cross-coupling reactions, as well as threefold benzoannelation involving tetrachlorothiophene-S,S-dioxide and PET-induced dehalogenation of highly chlorinated septiphenyl derivatives.",10.1055/s-2006-951497,2006-10-25,0.6670011024831568
Journal of the American Chemical Society,Total Synthesis of Akuammiline Alkaloid (−)-Vincorine via Intramolecular Oxidative Coupling,"An asymmetric total synthesis of the Akuammiline alkaloid (-)-vincorine (18 steps from 5-methoxytryptamine, 5% overall yield) is described. The key steps include Pd-catalyzed direct C-H functionalization of indole derivatives, organocatalyzed asymmetric Michael addition of aldehydes to alkylidene malonates, and intramolecular oxidative coupling between indole and malonate moieties.",10.1021/ja303602f,2012-05-22,0.6669343434697432
Synlett,"A New Synthetic Route to (S)-Chroman Aldehyde, a Key Chiral Precursor of Vitamin E","All articles of this category A highly stereocontrolled synthetic route to ( S )-chroman aldehyde has been developed which starts with trimethyl- p -hydroquinone and ( R )-glyceraldehyde acetonide and employs as key steps the Michael addition of the aromatic copper species onto the ( R )-4-acryloyl-1,3-dioxolane followed by the highly diastereoselective methylation of the resulting ketone adduct. chroman aldehyde - diastereoselectivity - glycerketone - Michael addition - vitamin E",10.1055/s-2001-14642,2001-01-01,0.6669340015723675
Synthesis,A New Strategy for the Synthesis of (±)-Lupinine and (±)-Epilupinine via Cyclization of α-Sulfinyl Carbanions,(±)-Lupinine and (±)-epilupinine have been prepared starting from commercially available δ-valerolactam. The synthetic route involves the advantages of the cyclization based on α-sulfinyl carbanions.,10.1055/s-2008-1067027,2008-05-26,0.6669149714557396
Journal of the American Chemical Society,"Total Synthesis of Spiruchostatin A, a Potent Histone Deacetylase Inhibitor","The total synthesis of spiruchostatin A was accomplished, unambiguously confirming its structure. Key steps included the use of the Nagao thiazolidinethione auxiliary for a diastereoselective acetate aldol reaction and as an activated acylating agent for amide formation, and macrolactonization by the Yamaguchi protocol. Spiruchostatin A is shown to have biological activity similar to that of FK228, a potent histone deacetylase (HDAC) inhibitor in clinical trials. The spiruchostatin A analogue, epimeric at the beta-hydroxy acid, is inactive, highlighting the importance of stereochemistry at this position for interactions with HDACs.",10.1021/ja039258q,2004-01-09,0.666911378850691
Journal of Organic Chemistry,A Facile Asymmetric Route to (−)-Aphanorphine,"8O-methylaphanorphine was synthesized from 4-methoxyphenylacetaldehyde in 36% overall yield and in nine steps, featuring the formation of ring B via a Friedel-Crafts alkylative cyclization with the concomitant stereospecific introduction of the benzylic quaternary carbon center. The current work constitutes an efficient enantioselective formal synthesis of 3-benzazepine marine alkaloid (-)-aphanorphine.",10.1021/jo0348726,2003-09-13,0.6668817789793215
Journal of Organic Chemistry,Enantioselective Synthesis of (<i>R</i>)-Tolterodine via CuH-Catalyzed Asymmetric Conjugate Reduction,"An efficient and highly enantioselective method for the preparation of (R)-tolterodine is described. The synthesis was performed by CuH-catalyzed asymmetric conjugate reduction of a beta,beta-diaryl-substituted unsaturated nitrile as a key step, which is prepared by a stereoselective hydroarylation of alkynenitrile with aryl boronic acid. The synthesis was accomplished without employing the protection-deprotection sequence.",10.1021/jo900530s,2009-04-27,0.6668688025242255
Tetrahedron,The asymmetric hydrogenation of 2-phenethylacrylic acid as the key step for the enantioselective synthesis of Citralis Nitrile®,,10.1016/j.tetlet.2006.10.129,2006-11-16,0.6668600448974068
Synthesis,A Novel Synthesis of the Antidepressant Agomelatine,"Agomelatine was synthesized from (2-methoxynaphthalene-8-yl)oxoacetic acid in a four-step approach involving borane reduction, semipinacol rearrangement of the resulting diol, ald­oxime formation, and Ra-Ni hydrogenation/acetylation in 51% overall yield. The reaction sequence includes a novel one-pot conversion of an aldoxime into an N-acetylamine. The synthetic route could be useful as a new approach towards N-acetylarylethyl­amines.",10.1055/s-0030-1258968,2010-11-09,0.6668370883697506
Organic Process Research & Development,"Development of a Commercial Manufacturing Route to 2-Fluoroadenine, The Key Unnatural Nucleobase of Islatravir","We report the practical synthesis of a key fragment of islatravir (MK-8591), a novel nucleoside reverse transcriptase translocation inhibitor (NRTTI) currently under investigation for treatment and pre-exposure prophylaxis (PrEP) against HIV infection. The fragment, the unnatural nucleobase 2-fluoroadenine, is incorporated into MK-8591 via a biocatalytic aldol-glycosylation cascade, which imposes stringent requirements for its synthesis and isolation. Presented herein is the development work leading to a practical, scalable route from guanine, featuring a dual fluorination approach to a novel 9-THP-2,6-difluoropurine intermediate that enables a mild, highly selective, direct amination. This one-pot fluorination/amination sequence utilizes a direct isolation to deliver high purity 9-THP-2-fluoroadenine, which features ideal properties with respect to reactivity, solubility, and crystallinity. An acid-catalyzed liberation of 2-fluoroadenine in aqueous buffer delivers the appropriate purity profile to facilitate the enzymatic cascade to access MK-8591.",10.1021/acs.oprd.0c00304,2020-07-31,0.6668361940343356
Journal of Organic Chemistry,Stereoselective Synthesis of the IDO Inhibitor Navoximod,"A highly efficient asymmetric synthesis of the IDO inhibitor navoximod, featuring the stereoselective installation of two relative and two absolute stereocenters from an advanced racemic intermediate, is described. The stereocenters were set via a crystallization-induced dynamic resolution along with two selective ketone reductions: one via a biocatalytic ketoreductase transformation and one via substrate-controlled hydride delivery from LiAlH(O t- Bu) 3 . Following this strategy, navoximod was synthesized in 10 steps from 2-fluorobenzaldehyde and isolated in 23% overall yield with 99.7% ee and high purity.",10.1021/acs.joc.1c02994,2022-03-23,0.6668312561496553
European Journal of Organic Chemistry,Concise Synthesis of a New Chiral Cyclopentenone Building Block for Prostaglandins and their Derivatives,"(4 R ,5 R )‐4,5‐ O ‐isopropylidene‐2‐(dimethoxyphosphoryl)cyclopen‐2‐enone was obtained in enantiomerically pure form in four steps starting from commercially available 2,3‐ O ‐isopropylidene‐D‐erythronolactone. The key steps involved are diastereoselective lactone ring opening leading in a one‐pot procedure to the ε‐silyloxy Weinreb‐type amide, and the cyclopentenone ring formation by the rhodium catalyzed carbenoid cyclization of the corresponding ε‐silyloxy‐α‐diazo‐β‐ketophosphonate followed by the elimination of tert ‐butyldimethylsilanol. During the synthetic study on the construction of the cyclopentanone ring by the intramolecular nucleophilic substitution reaction of an anion generated from ε‐bromo‐β‐ketophosphonate, the formation of cyclopropane derivative was observed. This stereochemical outcome was rationalized using quantum chemical calculations.",10.1002/ejoc.201900102,2019-03-25,0.6668284453924666
Organic Letters,An Approach to the Skeleton of the Securinega Alkaloids. The Total Synthesis of (±)-Securinine,[structure: see text]. The concise total synthesis of securinine in nine steps from readily available starting materials is described. Key steps of the synthesis include an addition of a silyloxyfuran to an in situ generated iminium ion and a novel ring closing metathesis reaction.,10.1021/ol0070482,2001-02-06,0.6667644897707774
Journal of the American Chemical Society,Next-Generation Total Synthesis of Vancomycin,"A next-generation total synthesis of vancomycin aglycon is detailed that was achieved in 17 steps (longest linear sequence, LLS) from the constituent amino acid subunits with kinetically controlled diastereoselective introduction of all three elements of atropisomerism. In addition to new syntheses of three of the seven amino acid subunits, highlights of the approach include a ligand-controlled atroposelective one-pot Miyaura borylation–Suzuki coupling sequence for introduction of the AB biaryl axis of chirality (>20:1 dr), an essentially instantaneous and scalable macrolactamization of the AB ring system nearly free of competitive epimerization (>30:1 dr), and two room-temperature atroposelective intramolecular S N Ar cyclizations for sequential CD (8:1 dr) and DE ring closures (14:1 dr) that benefit from both preorganization by the preformed AB ring system and subtle substituent effects. Combined with a protecting group free two-step enzymatic glycosylation of vancomycin aglycon, this provides a 19-step total synthesis of vancomycin. The approach paves the way for large-scale synthetic preparation of pocket-modified vancomycin analogues that directly address the underlying mechanism of resistance to vancomycin.",10.1021/jacs.0c07433,2020-09-04,0.6667042348951503
Organic Process Research & Development,Development of a Chemoenzymatic Route for the Preparation of 6-Keto Estradiol: A Key Intermediate for Fulvestrant,"A novel synthetic route was developed to synthesize 6-keto estradiol ( 2 ), an intermediate in the synthesis of fulvestrant and analogues. Using norandrostenedione as a starting material, the target 2 was obtained through five step reactions including esterification, hydroxylation, oxidation, enzyme-catalyzed dehydrogenative aromatization, and enzyme-catalyzed reduction. In hydroxylation, phthalic anhydride (PA)/H 2 O 2 /pyridine was developed as a catalytic system to give the desired 6a and 6b in 90% yield under mild conditions. The enzyme 3-ketosteroid-Δ 1 -dehydrogenase (Δ 1 -KstD) was utilized for the dehydrogenative aromatization of the A ring in 7, while 17β-hydroxysteroid dehydrogenases (17β-HSDs) were employed for the stereoselective reduction of 17-keto in 8 . The related impurities and process parameters were studied in detail. In addition, the scale-up of this synthetic route was successfully executed on a 300.00 g scale, yielding 159.04 g of 6-keto estradiol ( 2 ) with a purity of 99.6% and an overall yield of 50% in five steps. Other notable features of this synthetic route included high yields, mild reaction conditions, and inexpensive and commercially available starting materials.",10.1021/acs.oprd.5c00356,2025-12-13,0.6667019354797553
Synthesis,An Improved Synthesis of 3-Furoic Acid,,10.1055/s-1971-21772,1971-01-01,0.6666749551408534
Synthesis,"An Improved Synthesis of 1,8-Naphthaldehydic Acid",,10.1055/s-1976-24003,1976-01-01,0.6666749551408534
Synthesis,Sulfuryl Chloride Promoted gem-Dichlorination–Dehydrochlorination in Alkyl Benzothiazinylacetates: Synthesis of the Skeleton of Trichochrome Pigments,"Chemo- and stereoselective total synthesis of the basic trichochrome skeleton is described starting from o -aminothiophenol and maleic anhydride in very good overall yield. The process involves the synthesis of the corresponding 1,4-benzothiazin-2-ylacetates followed by their sulfuryl chloride induced dihalogenation–dehydrohalogenation and a second condensation with o -aminothiophenol as key steps.",10.1055/s-0034-1378714,2015-06-24,0.6666651975980448
Synlett,An Improved Iodine-Catalyzed Aromatization Reaction and Its Application in the Synthesis of a Key Intermediate of Cannabidiol,"Abstract In this study, the development of an improved process for the synthesis of a key cannabidiol intermediate, methyl olivetolate, is described. The process involves an improvement of the iodine-catalyzed aromatization of cyclohexanone using potassium persulfate as an oxidant. This approach enabled for the efficient synthesis of methyl olivetolate with a 90% yield and 99.84% HPLC purity on a 5 kg scale. Additionally, a total of 19 cyclohexanone substrates afforded higher yields (71–92%) of m-diphenol compounds compared to the established methods.",10.1055/a-2301-2431,2024-04-09,0.6666209484452018
Organic Process Research & Development,A New Route for Manufacture of 3-Cyano-1-naphthalenecarboxylic Acid,"3-Cyano-1-naphthalenecarboxylic acid is an intermediate required for manufacture of tachykinin receptor antagonists. The 1,3-disubstitution pattern on the naphthalene skeleton complicates the synthesis of this cyano acid. Previous literature-based chemistry is unattractive for large-scale manufacture due to stoichiometric use of mercury salts, low yield, and other operational difficulties. An attractive new route has been developed by establishing the 1,3-substitution on the carbon atoms destined for only one-half of the naphthalene 2-ring system, via 3-bromocoumalate, and then building up the rest of the naphthalene ring system by Diels−Alder addition of 3-bromocoumalate to in situ-generated benzyne. The resulting 4-bromo-2-naphthoate was converted to the required cyanoacid by transformation of ester to nitrile followed by carbonylation of the bromo substituent. The new route has been scaled up successfully and offers significant advantages over previous literature chemistry in terms of improved process environmental implications, improved yield, lower cost, and improved robustness and ease of operation at larger scales of operation.",10.1021/op025571l,2002-12-17,0.6666142524185376
Tetrahedron,A new synthesis of deglyco-bleomycin A2 aiming at the total synthesis of bleomycin,,10.1016/s0040-4039(00)86880-x,1982-01-01,0.6665947572168256
Tetrahedron,"First total synthesis of the β-carboline alkaloids trigonostemine A, trigonostemine B and a new synthesis of pityriacitrin and hyrtiosulawesine",,10.1016/j.tetlet.2019.04.044,2019-04-29,0.6665947572168256
Tetrahedron,Total synthesis of coriandrin and 7-demethylcoriandrin via a new synthesis of isocoumarins,,10.1016/s0040-4039(00)00441-x,2000-05-01,0.6665947572168256
Tetrahedron,Improved synthesis of the northern hemisphere of epothilone A by a Sharpless asymmetric dihydroxylation,,10.1016/s0040-4039(99)01659-7,1999-10-01,0.6665777780265477
Organic Letters,A Concise Asymmetric Total Synthesis of (+)-Brevisamide,"A new protecting-group-free synthesis of the marine monocyclic ether (+)-brevisamide is reported. The enantioselective synthesis utilizes a key asymmetric Henry reaction and an Achmatowicz rearrangement for the formation of the tetrahydropyran ring. A penultimate Stille cross-coupling allows for an efficient installation of the conjugated (E,E)-diene side chain ultimately delivering (+)-brevisamide.",10.1021/ol201283n,2011-06-16,0.6665584313794303
Synthesis,Chemistry of Epoxysulfones: A New Route to Polyhydroxylated Pyrrolidines,"A new methodology for the synthesis of polyhydroxylated pyrrolidines using epoxysulfones is described. The synthesis of two natural glycosidase inhibitors, 1,4-dideoxy-1,4-imino-d-lyxitol and 1,4-dideoxy-1,4-imino-d-mannitol (DIM), is reported.",10.1055/s-2005-861792,2005-01-18,0.6665556979207032
Journal of the American Chemical Society,Tremorgenic Indole Alkaloids. The Total Synthesis of (−)-Penitrem D,"A convergent, stereocontrolled total synthesis of the architecturally complex tremorgenic indole alkaloid (-)-penitrem D (4) has been achieved. Highlights of the synthesis include an efficient, asymmetric synthesis of the western hemisphere; the stereocontrolled assembly of the I-ring; discovery of a novel autoxidation to introduce the C(22) tertiary hydroxyl group, required for tremorgenic activity; union of fully elaborated eastern and western hemispheres, exploiting an indole synthetic protocol developed expressly for this purpose; and a late-stage, stereoselective construction of the A and F rings exploiting a Sc(OTf)(3-)promoted reaction cascade. The longest linear sequence leading to (-)-penitrem D (4) was 43 steps.",10.1021/ja034842k,2003-06-11,0.6665342076327208
Organic Process Research & Development,A Practical Building Block for the Synthesis of Discodermolide,"A new highly diastereoselective and practical route to the lactone 6a which is used as a key building block for the total synthesis of the microtubule-stabilizing anticancer agent discodermolide is reported. This exploits the chiral auxiliary (4 R )-4-isopropyl-5,5-diphenyloxazolidin-2-one ( 7 ) which conveys crystallinity to the synthetic intermediates throughout the entire process. Purifications can thus be performed by recrystallization, avoiding chromatography to afford the final product in high enantiomeric purity. The overall efficiency is augmented by the facile recovery of the auxiliary by precipitation at the end of the sequence.",10.1021/op049950l,2004-05-26,0.6665222059550487
Organic Process Research & Development,A Concise and Efficient Synthesis of Dapagliflozin,"A concise and efficient synthesis of the SGLT-2 inhibitor dapagliflozin ( 1 ) has been developed. This route involves ethyl C -aryl glycoside 9 as the key intermediate, which is easily crystallized and purified as the crystalline n -propanol solvate with high purity (>98.5%). The tetra-O-unprotected compound 9 could be directly reduced to crude dapagliflozin with high diastereoselectivity. The final pure API product 1 was isolated and purified with high purity (>99.7%). The process has been implemented on a multikilogram scale.",10.1021/acs.oprd.9b00141,2019-06-27,0.666499129776171
Organic Process Research & Development,"Efficient Method for the Synthesis of Amino-1,3-Oxazines from Thioureas","The synthesis of a subtype-selective inhibitor BACE-1 inhibitor is presented. One of the key transformations in this sequence is the conversion of a thiourea to the bicyclic 1,3-aminooxazine. This article outlines the development and application of this method to the target molecule as well as further exploration of its scope and mechanism.",10.1021/acs.oprd.0c00369,2020-11-24,0.6664876590436383
Journal of Organic Chemistry,A New Asymmetric Synthesis of the Anti-Tumor Alkaloid (<i>R</i>)-(+)-Crispine A,"We report a novel, facile, and asymmetric approach for the synthesis of the anti-tumor alkaloid (+)-crispine A via a highly diastereoselective N-acyliminium cyclization reaction as a key synthetic step.",10.1021/jo071235x,2007-10-09,0.6664827423874488
Synthesis,Efficient Synthesis of New 8-Aryl Tricyclic Pyridinones,"New tricyclic pyridinones were synthesized from 6-bromo-2-chloromethyl-3-nitroimidazo[1,2-a]pyridine in four steps involving a Suzuki-Miyaura cross-coupling reaction and a direct olefination with diethyl ketomalonate as key steps. Subsequent one-pot reduction-cyclization provided new ethyl 8-aryl-2-oxo-1,2-dihydrodipyrido[1,2-a;3′,2′-d]imidazole-3-carboxylates.",10.1055/s-2006-942505,2006-08-01,0.6664752208479157
Journal of Organic Chemistry,A Short Synthesis of (+)-Cyclophellitol,"[reaction: see text] A new synthesis of (+)-cyclophellitol, a potent beta-glucosidase inhibitor, has been completed in nine steps from D-xylose. The key transformations involve a zinc-mediated fragmentation of benzyl-protected methyl 5-deoxy-5-iodo-xylofuranoside followed by a highly diastereoselective indium-mediated coupling with ethyl 4-bromocrotonate. Subsequent ring-closing olefin metathesis, ester reduction, olefin epoxidation, and deprotection then afford the natural product. This constitutes the shortest synthesis of (+)-cyclophellitol reported to date.",10.1021/jo051645q,2005-10-19,0.6663943013936258
Organic Letters,Total Synthesis of Caesalpinnone A,"Total synthesis of caesalpinnone A was achieved in 12 steps starting from resorcinol. Key features of the synthesis include BINOL-phosphoric acid catalyzed [4 + 2] cycloaddition, trans -selective nucleophilic substitution, deallylation/oxa-Michael addition cascade, and late-stage photo-Fries rearrangement.",10.1021/acs.orglett.9b04276,2019-12-26,0.6663754149891324
Organic Letters,First Total Synthesis of a Polyunsaturated Chromone Metabolite Isolated from the Brown Algae <i>Zonaria tournefortii</i>,"Starting from the ethyl ester of eicosapentaenoic acid, the first total synthesis of the marine natural product all-(Z)-5,7-dihydroxy-2-(4Z,7Z,10Z,13Z,16Z-nonadecapentaenyl)chromone has been achieved in six steps and in 14% overall yield.",10.1021/ol802635a,2008-12-23,0.6663529680830484
Synthesis,First Total Synthesis of (±)-Verrucosapyrone A,The first total synthesis of (±)-verrucosapyrone A has been achieved in 17% overall yield in five steps.,10.1055/s-2006-950358,2006-11-02,0.6663431202354766
Organic Letters,Synthesis of a Selective Estrogen Receptor Degrader via a Stereospecific Elimination Approach,"An efficient synthesis of a selective estrogen receptor degrader, GDC-0810, bearing a challenging stereodefined (E)-tetrasubstituted all-carbon olefin core, is reported. The described synthetic route involves a highly diastereoselective addition of an arylmagnesium reagent 3a to ketone 4, yielding the key tertiary alcohol 2a in >99:1 dr. The corresponding tert-butyl carbonate derivative was identified among other leaving groups to provide the desired olefin geometry in a 98:2 E/Z ratio via a concerted elimination. A four-step telescoped process was then developed starting from the tertiary alcohol 2a to produce GDC-0810 API as a pyrrolidine salt in 70% yield.",10.1021/acs.orglett.8b00035,2018-02-03,0.6663349684197531
European Journal of Organic Chemistry,"Total Synthesis of Mycenarubin A, Sanguinolentaquinone and Mycenaflavin B and their Cytotoxic Activities","Here we report the first total synthesis of the fungal alkaloids mycenarubin A, sanguinolentaquinone and mycenaflavin B. The pyrroloquinoline alkaloid mycenarubin A was obtained in 10 steps (21 % total yield, 92 % ee ) from the known key precursor 6,7‐bis(benzyloxy)indole by an asymmetric alkylation and a biomimetic ring closure as the key steps. The indolo‐6,7‐quinone sanguinolentaquinone was obtained in eight steps (28 % total yield). Mycenaflavin B was also obtained in eight steps starting from the same key precursor (total yield 15 %) by a biomimetic ring closure and an acid‐catalysed decarboxylation reaction as the key steps. The cytotoxic activities of mycenarubin A and mycenaflavin B were evaluated against mouse fibroblasts (L929) and human malignant melanoma cells (RPMI‐7951).",10.1002/ejoc.201800417,2018-04-17,0.6663327336844159
Synthesis,First Stereoselective Total Synthesis of Anti-Inflammatory Metabolite Penicillinolide A,"The first asymmetric total synthesis of penicillinolide A is described. Key steps of the synthesis involve Jacobsen’s hydrolytic kinetic resolution (HKR), chelation controlled allylation, Brown’s asymmetric allylation, hydroboration, and Yamaguchi lactonization.",10.1055/s-0037-1611040,2018-11-14,0.6663308750520848
Organic Process Research & Development,Toward the Development of a Manufacturing Process for Milvexian: Scale-Up Synthesis of the Side Chain,"Anticoagulants play a critical role in the prevention and treatment of thrombotic-driven cardiovascular diseases. Factor XIa (FXIa) inhibitors have the potential to improve the benefit/risk profile of existing anticoagulants through a safer bleeding profile in a variety of conditions where patients are predisposed to a high risk of thrombotic or bleeding events. To support the clinical development program of milvexian (BMS-986177/JNJ-70033093), a FXIa inhibitor that recently completed phase II clinical trials, we improved the discovery route to deliver the suitable quantity of key intermediate 1 for clinical supply. This paper describes our optimization of the Suzuki cross-coupling and how we simplified and improved the isolation of 4-trimethylsilyl-1,2,3-triazole 6 after the azidation–click sequence. On top of streamlining the processes for the chlorination and demethylation steps, we demonstrated that the recrystallization of the penultimate intermediate 7 was key to control the purity and the color of the desired 4-chloro-1,2,3-triazole 1, which could be obtained in a 70% yield over five steps.",10.1021/acs.oprd.2c00399,2023-04-03,0.6663214249078713
Organic Letters,Concise and Stereoselective Synthesis of the N<sub>7</sub>−C<sub>25</sub> Fragment of Psymberin,"[reaction: see text] The N7-C25 fragment of the potent and selective cytotoxic agent psymberin has been prepared through a short (12 linear steps, 15 total steps) and stereoselective sequence. Highlights of this route include a very rapid construction of the pentasubstituted arene, a substrate-controlled diastereoselective fragment coupling using a Mukaiyama aldol reaction, and an efficient entry into a key tetrahydropyranyl cyanide.",10.1021/ol0520267,2005-10-08,0.6662963041005421
European Journal of Organic Chemistry,"Synthesis of 7‐Bromo‐1,3‐diazapyrenes","An efficient synthetic route towards previously inaccessible 7‐bromo‐1,3‐diazapyrenes through an in‐melt peri ‐cyclization of readily available 7‐(5‐bromo‐3,4‐dihydropyrimidin‐4‐yl)‐1 H ‐perimidines is described.",10.1002/ejoc.201800703,2018-06-05,0.6662829918122107
Organic Letters,Enantiocontrolled Access to an Intermediate for Highly Functionalized Clovane-Type Terpenoids: Formal Synthesis of Rumphellclovane E,"We describe an enantiocontrolled route to a versatile intermediate for the synthesis of highly functionalized clovane-type terpenoids. The synthetic route commenced with ( R )-carvone, a commercially available and enantioenriched building block, and an oxygenative strategy was used to concisely access a clovane scaffold. One example of the versatility of the obtained intermediate was the formal synthesis of rumphellclovane E.",10.1021/acs.orglett.2c02960,2022-10-11,0.6662356186359457
Synthesis,An Efficient Synthesis of Katsube Nitrile: A Key Building Block for Eburnamine-Vincamine Alkaloids,"A novel synthesis of the Katsube nitrile is achieved via an efficient diastereoselective Pictet–Spengler cyclization of 3-ethyl-2-hydroxy-1-[2-(1 H -indol-3-yl)ethyl]-6-oxopiperidine-3-carbonitrile to construct the cis -[CD] rings in 1-ethyl-4-oxo-1,2,3,4,6,7,12,12b-octahydroindolo[2,3- a ]quinolizine-1-carbonitrile , and 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) catalyzed condensation of tert -butyl 4-cyano-4-(hydroxymethyl)hexanoate with tryptamine to assemble 4-cyano-4-(hydroxymethyl)- N -[2-(1 H -indol-3-yl)ethyl]hexanamide as the key steps.",10.1055/s-0033-1340988,2014-03-26,0.6662203489969611
Synthesis,Synthesis of Isoquinolinium-2-yl Amides via Silver(I)-Catalyzed Ring Closure of N′-(2-Alkynylbenzylidene)hydrazides,"An efficient one-pot protocol for the synthesis of isoquinolinium-2-yl amides starting from readily available hydrazides and 2-alkynylbenzaldehydes is described. The key step of the protocol is a silver(I)-catalyzed ring-closure of N′-(2-alkynylbenzylidene)hydrazides that are generated in situ. Isoquinolinium-2-yl amides derived from tert-butoxycarbonyl hydrazide could be further deprotected, delivering 2-aminoisoquinolinium trifluoroacetates.",10.1055/s-0030-1260219,2011-09-08,0.6662066428392655
Synthesis,Asymmetric Synthesis of Gonioheptolide A Analogues via an Organocatalytic Aldol Reaction as the Key Step,"An efficient asymmetric synthesis of the potential antitumor agent (–)-gonioheptolide A derivatives is described. By employing an ( S )-proline-catalyzed aldol reaction, the RAMP hydrazone α-alkylation methodology, and a diastereoselective reduction with zinc borohydride five stereocenters are established in the target compound. 4- epi -Methoxy-gonioheptolide A was obtained in ten steps in 15% overall yield and excellent diastereo- and enantiomeric excesses (de ≥95%, ee ≥99%).",10.1055/s-0032-1316803,2012-10-09,0.6662052170396504
Organic Letters,An Asymmetric Approach toward the <i>Aristotelia</i> Alkaloid (−)-Penduncularine,"We report a catalytic enantioselective total synthesis of an endocyclic alkene regioisomer of (-)-peduncularine, termed (-)-pseudo-peduncularine, and also a synthesis of its C7 epimer. Highlights of the syntheses include a new strategy for the construction of the peduncularine framework by palladium-catalyzed ynamide cycloisomerization/enamide reduction, which could be performed on a multigram scale. By introducing the indole side chain as a substituent on the ynamide, this approach contrasts with previous strategies that have relied on late-stage Fischer indole synthesis. Inversion of the C7 stereocenter installed in the cycloisomerization process could be readily achieved by temporary azabicycle ring opening, using an enamide hydrolysis/ketone reduction/Mitsunobu cyclization sequence. A catalytic asymmetric sulfonamidation of a racemic allylic benzoate enabled an enantioselective synthesis of (-)-pseudo-peduncularine.",10.1021/acs.orglett.5c02062,2025-07-14,0.6661738754344633
Organic Process Research & Development,Development of a Scalable Synthesis of BMS-978587 Featuring a Stereospecific Suzuki Coupling of a Cyclopropane Carboxylic Acid,A modified synthetic route to BMS-978587 was developed featuring a chemoselective nitro reduction and a stereospecific Suzuki coupling as the key bond formation steps. A systematic evaluation of the reaction conditions led to the identification of a robust catalyst/ligand/base combination to reproducibly effect the Suzuki reaction on large scale. The modified route avoided several challenges with the original synthesis and furnished the API in high overall yield and purity without recourse to chromatography.,10.1021/acs.oprd.8b00171,2018-07-11,0.6661613591954756
Tetrahedron,Alternative synthetic route to annulated diaminopyrimidines,,10.1016/j.tetlet.2014.05.057,2014-05-22,0.6661603494897957
Organic Letters,"NH<sub>4</sub>OAc Promoted Cyclocondensation of 3-(<i>o</i>-Allylphenyl)pentane-1,5-diones: Synthesis of Tetracyclic Benzofused 1-Azahomoisotwistanes","A facile two-step synthetic route for preparing the novel tetracyclic skeleton of benzofused 2,6-diaryl-1-azahomoisotwistanes 2 had been developed. The route was carried out by a one-pot tandem cross-coupling reaction of o-allylbenzaldehydes 1 with aryl methyl ketones 3, and NH(4)OAc mediated the cascade cyclocondensation reaction of the resulting 1,5-diketones 4 with the 3-o-allylphenyl group in good yield in two steps.",10.1021/ol301693s,2012-07-20,0.6661541555045665
Journal of the American Chemical Society,Total Synthesis of (+)-Cyanthiwigin U,A concise total synthesis of the tricyclic terpene cyanthiwigin U has been accomplished in 12 steps and 17% overall yield. The key step of the synthesis is a two-directional tandem metathesis reaction that forms the cyclohepta[e]indene core from a readily available bicyclo[2.2.2]octene.,10.1021/ja0509836,2005-03-26,0.6661470415052115
Journal of Organic Chemistry,Total Synthesis of (−)-Ardeemin,"Total synthesis of potent anti-MDR indole alkaloids (-)-ardeemin and its N-acyl analogues has been accomplished from L-tryptophan with about 2% overall yield in 20 steps. The key step depended on the newly developed three-step one-pot cascade reaction of 7 with diazoester 8 via intermolecular cyclopropanation, ring opening, and ring closure to assemble the chiral 3-substituted hexahydropyrrolo[2,3-b]indole 4a.",10.1021/jo802216z,2008-11-13,0.6661097638690382
Tetrahedron,"First total synthesis of martefragin A, a potent inhibitor of lipid peroxidation isolated from sea alga",,10.1016/s0040-4039(98)01228-3,1998-08-01,0.6661006768206722
Organic Process Research & Development,Development of a Scaleable Synthesis of a 3-Aminopyrazinone Acetamide Thrombin Inhibitor,"A scaleable route to 2-{3-[(2,2-difluoro-2-(2-pyridyl)ethyl)amino]-6-chloro-2-oxohydropyrazinyl}- N -[(3-fluoro(2-pyridyl))methyl]acetamide 1 is described in which various scaleup issues were addressed to provide a safe, efficient, and robust route for the preparation of multi-kilo amounts of the compound. The use of expensive and toxic reagents, notably sodium azide, TMS-cyanide, and Deoxo-Fluor, and the need for specialist equipment were overcome in the preparation of the key fluorinated intermediates 2,2-difluoro-2-(2-pyridyl)ethylamine 3 and 2-aminomethyl-3-fluoropyridine 2 . With minimal isolations and through processing of intermediates, the thrombin inhibitor 1 was isolated in 36% overall yield.",10.1021/op0341420,2004-01-29,0.6660677028075753
Synthesis,"A Practical, Efficient Synthesis of 5-Amino-7-azaindole","A much improved, workable synthesis of 5-amino-7-azaindole is described in 66% overall yield starting from 2-amino-5-nitropyridine. The key stage involves a microwave promoted heteroannulation reaction of a pyridine alkyne.",10.1055/s-2005-872088,2005-07-20,0.6660425371376738
Journal of the American Chemical Society,"A Biomimetically Inspired, Efficient Synthesis of the South 7 Hemisphere of Cephalostatin 7","Synthesis of the South 7 hemisphere of cephalostatin 7 is described applying a second-generation synthetic strategy, which retains all the existing carbons in hecogenin acetate 1. TFAT (trifluoroacetyl trifluoromethanesulfonate)-assisted E-ring opening yields the key D-ring cyclopentadiene. A facially selective [4 + 2] cycloaddition between a series of steroidal D-ring dienes and singlet oxygen was conformationally directed by the C21-Me stereochemistry of the side chain. Sharpless asymmetric dihydroxylation of the terminal olefin provides (S)-C25-OH. An acid-catalyzed SN2' intramolecular alkylation of an acetal oxygen was followed by a one-pot sequence of beta-elimination and spiroketalization. The new route provides a practical 16-operation synthesis of the South 7 hemisphere (20% overall), as well as a model for construction of the crucial North 1 hemisphere.",10.1021/ja0531935,2005-09-03,0.6660357400170338
Synlett,Total Synthesis of Sperabillin A and C,"The first total synthesis of sperabillin A and an improved total synthesis of sperabillin C have been achieved in 11 steps from N-Boc-O-methyl-l-tyrosine. The stereoselective pathway to the core (3R,5R)-3,6-diamino-5-hydroxyhexanoic acid involves an Arndt-Eistert homologation, an asymmetric Henry reaction and a ruthenium tetroxide-catalyzed oxidative degradation of a benzene ring as key steps.",10.1055/s-2005-917106,2005-01-01,0.6660119950130714
Journal of Organic Chemistry,Synthesis of Lamellarin D Trimethyl Ether and Lamellarin H via 6π-Electrocyclization,"An electrocyclic ring closure of a 2-azapentadienyl anion generated in situ from a chalcone and glycine ester is the key step of an efficient synthesis of the pyrrole core of the lamellarin alkaloids. A recently developed scalable one-pot procedure provides multigram quantities of a 3,5-diaryl-4-iodopyrrole-2-carboxylate intermediate which is transformed in four further high-yielding operations including a one-pot Pomeranz-Fritsch alkylation/cyclization and an Ullmann-type lactone ring closure into the pentacyclic lamellarin skeleton.",10.1021/acs.joc.5b02194,2015-10-16,0.6660079641851444
Organic Letters,Stereocontrolled Synthesis of the AB Rings of Samaderine C,"A concise synthesis of the AB rings of samaderine C (12 steps, 8 isolation steps, 7.8% overall yield), a quassinoid with antifeedant and insecticidal activity, is described. The development of the first general approach to the trans-1,2-diol A-ring motif in samaderine C and other quassinoids is a key feature. The trans-1,2-diol is crafted via stereoselective α-hydroxylation (of a silyl enol ether) and reduction, a strategy that has much potential for quassinoid synthesis.",10.1021/ol303385a,2013-01-09,0.6660079129247771
Organic Letters,"A Short, Organocatalytic Formal Synthesis of (−)-Swainsonine and Related Alkaloids","A short synthesis of hydroxyalkyl dihydropyrroles has been developed that involves the coupling of propargylamines with α-chloroaldehydes, followed by Lindlar reduction and a one-pot epoxide formation/opening sequence. The application of this process to the synthesis of unnatural iminosugars and a formal synthesis of (-)-swainsonine is described.",10.1021/ol400566j,2013-04-03,0.6659894293187899
Tetrahedron,A new synthetic route to 3-polyfluoroalkyl-containing pyrroles,,10.1016/j.tetlet.2007.12.048,2008-01-08,0.6659811707162734
Journal of Organic Chemistry,Diastereoselective and Scalable Synthesis of 6-(<i>S</i>)-Hydroxycannabidivarin,"The synthesis of 6-( S )-hydroxycannabidivarin was required to assess its biological activity in the treatment of neurological disorders. A novel and scalable synthesis has been developed where the key step involves a Friedel–Crafts alkylation of phloroglucinol with (1 S,2 R,5 R )-2-hydroxy-2-methyl-5-(prop-1-en-2-yl)cyclohex-3-en-1-ylbenzoate. Careful optimization of the reaction conditions identified trifluoromethanesulfonic acid in isopropyl acetate as the best catalyst/solvent combination, providing optimum regioselectivity, diastereoselectivity, and yield for this step. This enabled the multigram synthesis of 6-( S )-hydroxycannabidivarin in 10 steps from S -(+)-carvone.",10.1021/acs.joc.3c01057,2023-08-01,0.6659711726311685
Tetrahedron,"Enantioselective cyclization of chiral butane-1,4-diols to chiral tetrahydrofurans: synthesis of chiral trans-2-(3-methoxy-5-methylsulfonyl-4-propoxyphenyl)-5-(3,4,5-trimethoxyphenyl)tetrahydrofuran (L-659,989), a potent PAF-receptor antagonist",,10.1016/s0040-4039(00)82307-2,1988-01-01,0.6659701440344418
Organic Letters,A Practical Six-Step Synthesis of (<i>S</i>)-Camptothecin,An asymmetric synthesis of (S)-camptothecin (1) has been accomplished in six steps starting from two commercially available heterocycles. [reaction: see text],10.1021/ol0169271,2001-11-22,0.665964201668913
Journal of the American Chemical Society,Asymmetric Total Synthesis of the Rearranged Steroid Phomarol Enabled by a Biomimetic S<sub>N</sub>2′ Cyclization,"Phomarol is a structurally unusual 1(10 → 19) abeo -steroid with a pseudo-symmetrical cycloheptene-1,3-diol motif, an aromatic B ring, and a densely functionalized tetrahydropyran ring. Herein, we report a 13-step synthesis of this natural product from inexpensive sitolactone by means of a convergent fragment-coupling approach. Key transformations include a diastereoselective allylboration, a decarboxylative elimination, a Schönecker–Baran C–H hydroxylation, a biomimetic S N 2′ cyclization, and a late-stage 6π electrocyclization. Mechanistic studies indicate that the pivotal formation of the tetrahydropyran ring occurs via a silyl migration/intramolecular S N 2′ cyclization cascade rather than via an epoxide-opening process.",10.1021/jacs.3c02817,2023-04-12,0.665931867443775
Journal of Organic Chemistry,"A Practical Synthesis of 2-((1<i>H</i>-Pyrrolo[2,3-b]pyridine-4-yl)methylamino)-5- fluoronicotinic Acid","A practical synthesis of a key pharmaceutical intermediate, 2-[(1H-pyrrolo[2,3-b]pyridine-4-yl)methylamino]-5-fluoronicotinic acid (1), is described. To introduce the aminomethyl moiety of 2 via a palladium-catalyzed cyanation/reduction sequence, a regioselective chlorination of 7-azaindole via the N-oxide was developed. A highly selective monodechlorination of 2,6-dichloro-5-fluoronicotinic acid was discovered to afford the nicotinic acid 3. The two building blocks 2 and 3 were then coupled to complete the preparation of 1.",10.1021/jo0602571,2006-04-05,0.6659255429698734
Organic Letters,Total Synthesis of “Aliskiren”: The First Renin Inhibitor in Clinical Practice for Hypertension,"We report a ""macrocycle route"" toward aliskiren, a drug presently marketed for the treatment of hypertension, using a highly stereocontrolled approach starting from a common ""isopropyl chiron"". Highlights of the synthesis include a challenging RCM reaction to produce a nine-membered unsaturated lactone, a highly stereoselective catalytic Du Bois aziridination, and a regio- and diastereoselective aziridine ring-opening to a vicinal amino alcohol.",10.1021/ol100427v,2010-03-17,0.6659215443137401
European Journal of Organic Chemistry,Convenient Synthesis of 3‐Glycosylated Isocoumarins,"A new route for the synthesis of 3‐substituted and 8‐hydroxy‐3‐substituted isocoumarins was developed by modified Julia olefination for initial C–C bond formation between aldehydes and benzylic sulfones. Palladium‐catalyzed Meinwald rearrangement was used as a key step for the obtainment of ketone intermediates, which – upon base‐promoted intramolecular cyclization – afforded the desired isocoumarins. The developed method paves the way to hitherto unknown 3‐glycosylisocoumarins, in general, and 3‐glucosylisocoumarins, in particular, wherein the glucosyl moiety is attached to the pyrone ring of the isocoumarin framework.",10.1002/ejoc.201601264,2016-11-10,0.665906167046862
Organic Letters,New Synthetic Route for the Enantioselective Total Synthesis of Salinosporamide A and Biologically Active Analogues,[reaction: see text] A total synthesis of the salinosporamide analogue 3 is described that starts with the novel cyclization 4 --> 5.,10.1021/ol0508734,2005-05-26,0.665901545926407
Journal of Organic Chemistry,Total Synthesis of (+)-Quassin,"A total synthesis of (+)-quassin from naturally occurring (S)-(+)-carvone is described. The total number of steps was 28, and the overall yield was about 2.6%. The synthetic strategy for the construction of the tetracyclic carbon framework was based on a C-->ABC-->ABCD ring annulation sequence, involving an aldol reaction, an intramolecular Diels-Alder reaction, and an intramolecular acylation as the key steps. Subsequent functionalization of ring A and ring C then afforded the target (+)-quassin.",10.1021/jo000877g,2000-09-28,0.6658852687619525
Synthesis,Efficient Construction of a Doubly Functionalized Trisoxazole Derivative Relevant to the Synthesis of the Novel Telomerase Inhibitor Telomestatin and its Analogues,"An efficient construction of a suitably functionalized trisoxazole derivative related to telomestatin was developed from l-serine, which involved three sequential oxazoline cyclization-oxidation steps in an overall yield of 11% in a linear sequence of twelve steps.",10.1055/s-2006-926415,2006-04-01,0.6658802774139629
Synthesis,An Alternative Formal Synthesis of (S)-(+)-Vigabatrin,"Abstract An improved synthesis of chirally pure advanced pyrrolidone intermediate of the (S)-(+)-vigabatrin, an antiseizure active pharmaceutical ingredient (API) is reported. The synthesis is developed using commercially available, cheaper amino acid (R)-methionine. Meldrum’s acid served as a two-carbon homologation unit to access the pyrrolidone intermediate in a short synthetic sequence. The sequence to pyrrolidone intermediate is scalable and eludes the use of organometallic pyrophoric reagents on a large scale.",10.1055/s-0042-1751470,2023-07-03,0.6658429175768323
Tetrahedron,Alternative route towards the convergent synthesis of a human purine nucleoside phosphorylase inhibitor—forodesine HCl,,10.1016/j.tetlet.2009.06.137,2009-07-09,0.6658234292388535
Journal of the American Chemical Society,Enantioselective Synthesis and Structure Revision of Solandelactone E,"The first total synthesis of solandelactone E has been achieved by a novel and convergent strategy that required 23 steps. The synthesis features a diastereoselective acetal-directed cyclopropanation of an electron-deficient diene, a Sharpless asymmetric dihydroxylation, and a [2,3]-sigmatropic rearrangement of a selenoxide intermediate.",10.1021/ja068270q,2006-12-30,0.6658009340282878
Journal of the American Chemical Society,Total Synthesis of (−)-Bafilomycin A<sub>1</sub>,"A highly stereoselective total synthesis of (-)-bafilomycin A(1), the naturally occurring enantiomer of this potent vacuolar ATPase inhibitor, is described. The synthesis features the highly stereoselective aldol reaction of methyl ketone 8b and aldehyde 60c and a Suzuki cross-coupling reaction of the highly functionalized advanced intermediates 12 and 39. Vinyl iodide 12 was synthesized by a 14-step sequence starting from the readily available beta-alkoxy aldehyde 14, while the vinylboronic acid component 39 was synthesized by a nine-step sequence from beta-hydroxy-alpha-methyl butyrate 44 via a sequence involving the alpha-methoxypropargylation of chiral aldehyde 49 with the alpha-methoxypropargylstannane reagent 54. Syntheses of fragments 12 and 39 also feature diastereoselective double asymmetric crotylboration reactions to set several of the critical stereocenters. The Suzuki cross-coupling of 12 and 39 provided seco ester 40, which following conversion to the seco acid underwent smooth macrolactonization to give 41. The success of the macrocyclization required that C(7)-OH be unprotected. The Mukaiyama aldol reaction between aldehyde 60c and the TMS enol ether generated from 8b provided aldol 65 with high diastereoselectivity. Finally, all silicon protecting groups were removed by treatment of the penultimate intermediate 65 with TAS-F (tris(dimethylamino)sulfonium difluorotrimethylsilicate), thereby completing the total synthesis of (-)-bafilomycin A(1).",10.1021/ja017885e,2002-05-23,0.6657468895192391
Journal of Organic Chemistry,"Telescoped Process to Manufacture 6,6,6-Trifluorofucose via Diastereoselective Transfer Hydrogenation: Scalable Access to an Inhibitor of Fucosylation Utilized in Monoclonal Antibody Production","IgG1 monoclonal antibodies with reduced glycan fucosylation have been shown to improve antibody-dependent cellular cytotoxicity (ADCC) by allowing more effective binding of the Fc region of these proteins to T cells receptors. Increased in vivo efficacy in animal models and oncology clinical trials has been associated with the enhanced ADCC provided by these engineered mAbs. 6,6,6-Trifluorofucose (1) is a new inhibitor of fucosylation that has been demonstrated to allow the preparation of IgG1 monoclonal antibodies with lower fucosylation levels and thus improve the ADCC of these proteins. A new process has been developed to support the preparation of 1 on large-scale for wide mAb manufacture applications. The target fucosylation inhibitor (1) was synthesized from readily available d-arabinose in 11% overall yield and >99.5/0.5 dr (diastereomeric ratio). The heavily telescoped process includes seven steps, two crystallizations as purification handles, and no chromatography. The key transformation of the sequence involves the diastereoselective preparation of the desired trifluoromethyl-bearing alcohol in >9/1 dr from a trimethylsilylketal intermediate via a ruthenium-catalyzed tandem ketal hydrolysis-transfer hydrogenation process.",10.1021/acs.joc.6b00646,2016-05-06,0.6657025832332532
Journal of the American Chemical Society,Asymmetric Total Synthesis of (−)-Vinigrol,"A new strategy was developed for the asymmetric total synthesis of (-)-vinigrol. The strategy involved a linear sequence of 15 steps from 3-methyl-butanal (14 steps from chloro-dihydrocarvone) and did not need protecting groups. The synthetically challenging 1,5-butanodecahydronaphthalene core was constructed efficiently via a type II intramolecular [5+2] cycloaddition, followed by a unique ring-contraction cascade.",10.1021/jacs.9b08983,2019-09-23,0.6656210758857256
Organic Letters,Formal Total Synthesis of (±)-Cephalotaxine and Congeners via Aryne Insertion Reaction,"The formal total synthesis of pentacyclic core alkaloid, (±)-cephalotaxine is achieved in nine steps from known 2-allylpyrrolidine-2-carboxaldehyde using aryne insertion reaction as a key step in 10% overall yield. The developed novel strategy enabled easy access to cephalotaxine congeners.",10.1021/acs.orglett.6b00659,2016-04-12,0.665608486650622
Synthesis,An Efficient Synthesis of Enantiomerically Pure (<i>R</i>)-(2-Benzyloxyethyl)oxirane from (<i>S</i>)-Aspartic Acid,All articles of this category A 3-step synthesis of the title compound from ( S )-aspartic acid is described. The overall yield of this process is 65% and the enantiomeric purity (ep) of the product is greater than 99%,10.1055/s-1992-26176,1992-01-01,0.6656030407553287
Journal of Organic Chemistry,"Total Synthesis of Terprenin, a Novel Immunosuppressive <i>p</i>-Terphenyl Derivative","We achieved a total synthesis of terprenin, a novel potent immunoglobulin E antibody suppressant which was obtained from the fermentation broth of Aspergillus candidus RF-5672 and has a highly oxygenated p-terphenyl skeleton with a prenyloxy side chain. The key steps relied on the Suzuki reaction to construct the terphenyl skeleton and on regioselective halogenations to selectively combine the aromatic rings. The highly efficient and practical production of this important natural product offers promise for the development of a new type of antiallergic drug.",10.1021/jo980349t,1998-08-01,0.6655927469047843
Journal of Organic Chemistry,"A Stereocontrolled, Efficient Synthetic Route to Bioactive Sphingolipids:  Synthesis of Phytosphingosine and Phytoceramides from Unsaturated Ester Precursors via Cyclic Sulfate Intermediates","An efficient and highly enantioselective method for the preparation of D-ribo- and L-lyxo-phytosphingosines (1a,b, respectively) and phytoceramides (2a,b) has been developed. The key steps in the syntheses are as follows: (i) osmium-catalyzed asymmetric dihydroxylation of 4-O-protected (E)-alpha,beta-unsaturated ester 5 (generated by dihydroxylation of 1-hexadecene, followed by oxidation to the aldehyde and Horner-Wadsworth-Emmons olefination), (ii) conversion to cyclic sulfate intermediate 7, and (iii) regioselective alpha-azidation of 7. Reduction of 4-O-protected 2-azido ester 8 via alpha-azidolactone 9 afforded phytosphingosine 1a. Staudinger reduction of the azido group of 8, followed by in situ N-acylation in aqueous media and reduction of the ester functionality with NaBH(4)/LiBr, provided phytoceramide 2a. By using a similar approach, phytosphingosine 1b was synthesized. D-erythro-4, 5-Dihydrosphingosine 1c and D-erythro-4,5-dihydroceramide 2c were synthesized in high yield from 1-hexadecanol via cyclic sulfate intermediate 15. The desired configurations at C-2, C-3, and C-4 of the sphingoid chain can be accessed readily by the route described here.",10.1021/jo001225v,2000-10-06,0.6655915571219303
Synlett,"A Practical Synthesis of (1<i>S</i>,2<i>R</i>)-1-Amino-2-indanol, a Key Component of HIV Protease Inhibitor, Indinavir","All articles of this category The synthesis of (1 S ,2 R )-1-amino-2-indanol, a key component of HIV protease inhibitor, is accomplished in eight steps from d-phenylalanine. The starting material is converted into 2-acetoxy-1-indanone in four steps involving intramolecular Friedel-Crafts cyclization. The stereochemically labile α-acetoxy ketone is hydrolyzed to 2-hydroxy-1-indanone using a catalytic amount of scandium triflate without any loss of the optical purity. Diastereoselective hydrogenation of α-hydroxy oxime, derived from the α-hydroxy ketone, gives the amino alcohol in 96% cis -selectivity. Optical purity of the starting material is perfectly retained throughout the transformations. indinavir - 1-amino-2-indanol - hydroxyindanone scandium triflate - hydrogenation",10.1055/s-1998-3126,1998-01-01,0.6655704629100496
Journal of Organic Chemistry,Convergent Formal Synthesis of (±)-Roseophilin,"A facile convergent synthesis of the tricyclic core 2 of roseophilin is described, which represents the shortest route so far for the formal synthesis of roseophilin. The key step was a tandem pyrrole acylation-Nazarov cyclization reaction to form the cyclopenta[b]pyrrole moiety 4.",10.1021/jo201949x,2011-11-18,0.6655578447845155
Synthesis,Total Synthesis of the Slime Mold Alkaloids Arcyroxocin A and B,"The synthesis of the slime mold pigments arcyroxocin A and B is described. The key step in the synthesis is the oxidative ring closure of an N-protected 3-(4-hydroxyindol-3-yl)-4-indol-3-ylmaleimide with DDQ/PPTS, which affords exclusively the desired arcyroxocin derivative. Attempts to obtain the arcyroxocin system from a 3-(4-hydroxyindolyl)-4-(2-oxoindolinyl)maleimide precursor were less successful and led to oxidative formation of a spiroindoline compound.",10.1055/s-0030-1258340,2010-12-08,0.6655523991217441
Organic Process Research & Development,"Practical Preparation of a 1,3,5-Trisubstituted Pyridazin-4(1<i>H</i>)-one Using Selective C<sub>1</sub> Unit Insertion and Cyclization","A novel and practical preparation of the selective phosphodiesterase 10A (PDE10A) inhibitor 1 having the core moiety of a 1,3,5-trisubstituted pyridazin-4(1 H )-one has been achieved. The facile preparation of 1 in 42% overall yield involves the following key features: (1) the finding that filling the headspace of the reaction vessel with Ar gas and controlling the flow rate of the gas were found to be important to complete the substitution of an aryl iodide with pyrazole; (2) synthesis of a 3-acetyl-5-methoxy-substituted pyridazin-4(1 H )-one via regioselective dimethylaminomethylenation of a diazo compound and simultaneous cyclization; and (3) regioselective ring formation of a 1,5-disubstituted pyrazole through reaction of a dimethylaminomethylene group with phenylhydrazine. In addition, an alternative synthesis of 1 via selective alkylation of 1-phenylpyrazole has been discovered.",10.1021/acs.oprd.8b00394,2019-02-04,0.665548507944414
Tetrahedron,"A convergent synthesis of an LTD4 antagonist, RG12525",,10.1016/s0040-4039(96)02460-4,1997-02-01,0.6655387657761135
Synlett,Synthetic Studies toward the Total Synthesis of Amphidinolide H1,"A convergent synthesis of the macrolide core as the immediate precursor to amphidinolide H1 is described, which features a palladium-catalyzed Stille cross-coupling, a methyl ketone diastereoselective aldol reaction, a Mitsunobu esterification, and an intramolecular ring-closing metathesis (RCM) reaction to construct the 26-membered macrocycle as key steps.",10.1055/s-2008-1032101,2008-02-26,0.6655111625030069
European Journal of Organic Chemistry,Total Synthesis of Berkeleyamide A and its 10‐<i>epi</i> Isomer,"Abstract A short and efficient synthesis of the novel cytotoxic natural product berkeleyamide A, isolated from a deep‐water Penicillium rubrum , has been accomplished. L ‐Leucinol was used as the only chiral starting material. A diastereoselective aldol condensation is the key step in the synthesis.",10.1002/ejoc.201000914,2010-09-23,0.6654734825737465
Organic Letters,Synthesis of Neokotalanol and Its Derivatives as Potent α-Glucosidase Inhibitors,"A novel synthesis of neokotalanol, a sulfonium type α-glucosidase inhibitor derived from the genus Salacia, was developed. The strategy efficiently constructs the d -manno-heptitol side chain from 2-hydroxyglycal via cyclopropanation and ring-opening reaction. Stereoselective borohydride reduction of a 2,3-dicarbonyl intermediate installed two key chiral hydroxy groups. This Wittig-free method uses nontoxic reagents and achieves gram-scale synthesis of a key intermediate, enabling its first structural modification that highlights the critical role of C-6′ hydroxyl for biological activity.",10.1021/acs.orglett.5c03549,2025-10-04,0.6654639622510152
Journal of Organic Chemistry,Diastereoselective FeCl<sub>3</sub>·6H<sub>2</sub>O/NaBH<sub>4</sub> Reduction of Oxime Ether for the Synthesis of β-Lactamase Inhibitor Relebactam,"Relebactam, a potent β-lactamase inhibitor, in combination with Primaxin is an FDA-approved (Recarbrio) treatment for serious and antibiotic-resistant bacterial infections. An efficient synthesis of key chiral piperidine intermediate 1 suitable for large-scale preparation of relebactam is described. The key steps include a unique highly diastereoselective FeCl 3 ·6H 2 O/NaBH 4 reduction of a chiral oxime ether and chemoselective amidation of the resulting unprotected pipecolic acid. Nuclear magnetic resonance studies and density functional theory calculations were carried out on the substrate–Fe(III) complexes, which shed light on diastereoselective reduction.",10.1021/acs.joc.9b02948,2019-12-18,0.6654619480202211
Organic Process Research & Development,Development of a One-Step Synthesis of 5-Amino-1<i>H</i>-imidazole-4-carboxamide,An innovative and efficient synthesis of 5-amino-1 H -imidazole-4-carboxamide (AIC) from commercially available hypoxanthine (∼$30/kg) is described. The development of the key hydrolysis step and a practical isolation enables a highly efficient one-step manufacturing process for AIC with minimal environmental impact and significant reduction of production cost.,10.1021/acs.oprd.1c00013,2021-03-09,0.6654585259645678
Organic Letters,"Platinum-Catalyzed α,β-Unsaturated Carbene Formation in the Formal Syntheses of Frondosin B and Liphagal","Formal syntheses of tetracyclic terpenoids frondosin B and liphagal are described. Both synthetic routes rely on the use of platinum-catalyzed α,β-unsaturated carbene formation for the key C-C bond forming transformations. The successful route toward frondosin B utilizes a formal (4 + 3) cycloaddition, while the liphagal synthesis features the vinylogous addition of an enol nucleophile as a key step. Both synthetic routes are discussed, revealing insights into structural requirements in the catalytic α,β-unsaturated carbene reaction manifold.",10.1021/acs.orglett.6b03682,2016-12-20,0.6654542870550224
Journal of Organic Chemistry,Asymmetric Synthesis of an<i>N</i>-Acylpyrrolidine for Inhibition of HCV Polymerase,"A practical asymmetric synthesis of a highly substituted N-acylpyrrolidine on multi-kilogram scale is described. The key step in the construction of the three stereocenters is a [3+2] cycloaddition of methyl acrylate and an imino ester prepared from l-leucine t-butyl ester hydrochloride and 2-thiazolecarboxaldehyde. The cycloaddition features novel asymmetric catalysis via a complex of silver acetate and a cinchona alkaloid, particularly hydroquinine, with complete diastereomeric control and up to 87% enantiomeric control. The alkaloid serves as a ligand as well as a base for the formation of the azomethine ylide or 1,3-dipole. Experiments have shown that the hydroxyl group of hydroquinine is a critical element for the enantioselectivities observed. The cycloaddition methodology is also applicable to methylvinyl ketone, providing access to either alpha- or beta-epimers of 4-acetylpyrrolidine depending on the reaction conditions utilized. The synthesis also highlights an efficient N-acylation, selective O- versus N-methylation, and a unique ester reduction with NaBH4-MeOH catalyzed by NaB(OAc)3H that not only achieves excellent chemoselectivity but also avoids formation of the undesired but thermodynamically favored epimer. The highly functionalized target is synthesized in seven linear steps from l-leucine t-butyl ester hydrochloride with all three isolated intermediates being highly crystalline.",10.1021/jo800062c,2008-03-22,0.6654437557061343
European Journal of Organic Chemistry,Morita–Baylis–Hillman Approach toward Formal Total Synthesis of Tamiflu and Total Synthesis of Gabaculine,"Abstract A Morita–Baylis–Hillman reaction mediated approach to the formal total synthesis of oseltamivir and the total synthesis of gabaculine is described. This strategy involves the enantiocontrolled preparation of Corey's intermediate in 22 % yield, which is prepared over 11 steps starting from N ‐ tert ‐butoxycarbonyl‐ L ‐serine methyl ester.",10.1002/ejoc.201300977,2013-09-13,0.6654202610106151
Organic Process Research & Development,Two Routes to 4-Fluorobenzisoxazol-3-one in the Synthesis of a 5-HT<sub>4</sub>Partial Agonist,"A potent 5-HT 4 partial agonist, 1 (PF-04995274), targeted for the treatment of Alzheimer’s disease and cognitive impairment, has been prepared on a multi-kilogram scale. The initial synthetic route, that proceeded through a 4-substituted 3-hydroxybenzisoxazole core, gave an undesired benzoxazolinone through a Lossen-type rearrangement. Route scouting led to two new robust routes to the desired 4-substituted core. Process development led to the efficient assembly of the API on a pilot plant scale under process-friendly conditions with enhanced throughput. In addition, crystallization of a hemicitrate salt of the API with pharmaceutically beneficial properties was developed to enable progression of clinical studies.",10.1021/acs.oprd.5b00389,2016-02-02,0.6654140975001918
Organic Process Research & Development,Development of a Practical Synthesis of an Aminoindanol-Derived M1 Agonist,An efficient and scalable synthesis of the clinical candidate 1 is described. The first-generation synthesis built the enantioenriched nitro-aminoindanol core from 6-nitroindanone using a five-step literature route. The second-generation route used a safe aromatic nitration protocol in the presence of the unprotected alcohol to afford the requisite nitro-aminoindanol in one step. Challenges addressed in the remainder of the synthesis include a nitro group reduction to afford ppm levels of unreacted Ar-NO 2 (a mutagen) and a novel amidine formation under mild conditions via DMAP/K 2 CO 3 -promoted reaction with a thioimidate-activated amide. A convenient protocol for freebasing the API was provided by stirring with solid K 2 CO 3 and monitoring disappearance of HI by reverse-phase HPLC.,10.1021/op800243q,2009-01-05,0.6654053717277406
Journal of the American Chemical Society,"Asymmetric Synthesis of the Aminocyclitol Pactamycin, a Universal Translocation Inhibitor","An asymmetric total synthesis of the aminocyclopentitol pactamycin is described. The title compound is delivered in 15 steps from 2,4-pentanedione. Critical to this approach was the exploitation of a complex symmetry-breaking reduction strategy to assemble the C1, C2, and C7 relative stereochemistry within the first four steps of the synthesis. Multiple iterations of this reduction strategy are described, and a thorough analysis of stereochemical outcomes is detailed. In the final case, an asymmetric Mannich reaction was developed to install a protected amine directly at the C2 position. Symmetry-breaking reduction of this material gave way to a remarkable series of stereochemical outcomes leading to the title compound without recourse to nonstrategic downstream manipulations. This synthesis is immediately accommodating to the preparation of structural analogs.",10.1021/ja409944u,2013-11-18,0.6653923567635149
Journal of Organic Chemistry,"An Asymmetric Synthesis of L-694,458, a Human Leukocyte Elastase Inhibitor, via Novel Enzyme Resolution of β-Lactam Esters","A convergent synthesis of [S-(R,S)]-2-[4-[(4-methylpiperazin-1-yl)carbonyl]phenoxy]-3,3-diethyl-N-[1-[3,4-(methylenedioxy)phenyl]butyl]-4-oxo-1-azetidinecarboxamide (L-694,458, 1), a potent human leukocyte elastase inhibitor, was achieved via chiral synthesis of key intermediates: (S)-3,3-diethyl-4-[4'-[(N-methylpiperazin-1-yl)carbonylphenoxy]-2-azetidinone (2) and (R)-alpha-propylpiperonyl isocyanate (3). Synthesis of beta-lactam 2 was achieved by a novel enantioselective lipase hydrolysis of ester 5 to produce (S)-3,3-diethyl-4-(4'-carboxyphenoxy)-2-azetidinone (6) (60% yield, three cycles, 93% ee) with isolation, epimerization, and recycling of the undesired (R)-ester 5. Isocyanate 3 was prepared by chiral addition of Zn(n-Pr)(2) to piperonal (98% yield, 99.2% ee), azide displacement and reduction to (R)-alpha-propylpiperonylamine (11) (58% yield, 85% ee), crystallization as the D-pyroglutamic acid salt (92% yield, 98.2% ee), and isocyanate formation (98% yield) with phosgene.",10.1021/jo960618k,1996-01-01,0.665315551694584
Journal of the American Chemical Society,A Convergent Total Synthesis of (±)-γ-Rubromycin,"An expeditious convergent total synthesis affords (±)-γ-rubromycin (1) in 4.4% overall yield. The longest linear sequence is 12 steps from commercial starting materials. The effort highlights a remarkable late-stage oxidative [3 + 2] cycloaddition for construction of the spiroketal, a regioselective carbonyl methylenation, a boron tribromide promoted deprotection, ortho- to para- naphthoquinone spiroketal rearrangement, and a tautomerization sequence.",10.1021/ja1115524,2011-03-31,0.6653060939800729
Organic Process Research & Development,"Practical Asymmetric Synthesis of RO5114436, a CCR5 Receptor Antagonist","A practical asymmetric synthesis of a 3,7-diazabicyclo[3.3.0]octane derivative ( 1 ), a representative of a new class of potent CCR5 receptor antagonists, is described. The benzylamine stereogenic center of 1 was introduced by a ruthenium-catalyzed asymmetric reductive amination using ( R )-MeOBIPHEP as ligand. Aldehyde 4, prepared by Parikh−Doering oxidation, was used without workup in the reductive amination reaction, which not only simplified the process but also overcame the instability of 4 . The 3,7-diazabicyclo[3.3.0]octane core was obtained by a [3 + 2] cycloaddition.",10.1021/op100020z,2010-03-10,0.6652384940452688
Journal of the American Chemical Society,First and Second Generation Total Synthesis of the Teicoplanin Aglycon,"Full details of studies leading to the total synthesis of the teicoplanin aglycon are provided. Key elements of the first generation approach (26 steps from constituent amino acids, 1% overall) include the coupling of an EFG tripeptide precursor to the common vancomycin/teicoplanin ABCD ring system and sequential DE macrocyclization of the 16-membered ring with formation of the diaryl ether via a phenoxide nucleophilic aromatic substitution of an o-fluoronitroaromatic (80%, 3:1 atropisomer diastereoselection) followed by 14-membered FG ring closure by macrolactamization (66%). Subsequent studies have provided a second generation total synthesis which is shorter, more convergent, and highly diastereoselective (22 steps, 2% overall). This was accomplished by altering the order of ring closures such that FG macrolactamization (95%) preceded coupling of the EFG tripeptide to the ABCD ring system and subsequent DE ring closure. Notably, DE macrocyclization via diaryl ether formation on substrate 57, the key intermediate in the latter approach incorporating the intact FG ring system, occurred with exceptional diastereoselection for formation of the natural atropisomer (>10:1, 76%) without problematic C(2)(3) epimerization provided the basicity of the reaction is minimized.",10.1021/ja003835i,2001-02-07,0.6652156356773715
Journal of Organic Chemistry,Synthesis of Septanosides through an Oxyglycal Route,"A new route to synthesize septanoside derivatives from protected 2-hydroxyglycals is reported. Ring expansion of a pyranoside to a septanoside was achieved through key reactions of a cyclopropanation, ring opening, oxidation, and reduction. Methyl septanoside derivatives, namely, methyl alpha-D-glycero-D-talo-septanoside and methyl alpha-D-glycero-l-altro-septanoside, were synthesized in an overall yield of 35% and 46%, respectively, from the corresponding protected 2-hydroxy glycals.",10.1021/jo070444e,2007-06-22,0.6652129765804998
Journal of Organic Chemistry,Total Synthesis of (±)-Cermizine B,"A practical synthesis of (±)-cermizine B was achieved. The nine-step synthesis mainly comprised two uninterrupted Michael additions including a highly diastereoselective 1,4-addition of 2-picoline to methyl 4-methyl-6-oxocyclohex-1-ene-1-carboxylate, Krapcho decarboxylation, a double reductive amination that resulted in ring closure and dearomatization of pyridine in 24% overall yield.",10.1021/acs.joc.7b02073,2017-10-03,0.6652030777995589
Journal of Organic Chemistry,Gram-Scale Total Synthesis of Carbazomycins A–D through Late-Stage Regioselective Demethylation of Aryl Methyl Ethers,"Gram-scale total synthesis of carbazomycins A-D is described. The total synthesis of carbazomycin A was achieved in 44% overall yield over six steps from symmetrical 5-chloro-1,2,3-trimethoxybenzene. The key aryne-mediated carbazole formation and methylation steps provided the multiply substituted carbazole. The regioselective demethylation of the trimethoxycarbazole was performed using boron trichloride. Thereafter, the phenolic hydroxy group was converted into the methyl group to provide carbazomycin A. Subsequent installation of the methoxy group realized the total synthesis of carbazomycin D. Regioselective demethylation was performed using 1-dodecanethiol, effecting the conversions of carbazomycins A and D into carbazomycins B and C, respectively.",10.1021/acs.joc.4c01613,2024-09-05,0.6651456231361202
Organic Letters,Asymmetric Synthesis of the Northern Half C1−C16 of the Bryostatins,"Starting from 8-oxabicyclo[3.2.1]oct-6-en-3-one and racemic 2,2-dimethyl-8-oxabicyclo[3.2.1]oct-6-en-3-one, the C1-C16 segment of the bryostatins has been synthesized in 30 steps and 9% overall yield (17 steps longest linear sequence). Fragment coupling by dithiane strategy and protecting group manipulations provided an advanced chemodifferentiated northern half segment.",10.1021/ol015551o,2001-02-27,0.6651439529597196
Organic Letters,Short and Efficient Synthetic Route to Methyl α-Trioxacarcinoside B and Anomerically Activated Derivatives,"A 9-step synthetic route to the complex carbohydrate methyl α-trioxacarcinoside B from 2-acetylfuran is described. Anomerically activated forms, including 1-phenylthio, 1-O-(4'-pentenyl), 1-fluoro, and 1-O-acetyl derivatives are also prepared.",10.1021/ol202315m,2011-09-29,0.6651175687975379
Organic Letters,Total Synthesis of Pyridovericin:  Studies toward the Biomimetic Synthesis of Pyridomacrolidin,"[reaction: see text] The total synthesis of the novel metabolite pyridovericin 1 is reported. The synthesis of this key intermediate in our proposed biomimetic synthesis of pyridomacrolidin 2 has been accomplished in good yield from readily available 2,4-dihydroxypyridine.",10.1021/ol0200504,2002-05-29,0.6651099310810491
Journal of Organic Chemistry,"A Convergent, Scalable Synthesis of HIV Protease Inhibitor PNU-140690","PNU-140690, an inhibitor of the HIV protease enzyme undergoing clinical evalution as a chemotherapeutic agent for treatment of AIDS, was synthesized by a convergent approach amenable to large-scale preparation in a pilot plant environment. The key step is the aldol addition of nitroaromatic ester (+)-8 to aldehyde 19e. The two stereocenters present in the target molecule were each set independently by resolution of enantiomers. Intermediates along the synthetic routes were chosen to maximize opportunities for isolation and purification by crystallization.",10.1021/jo9809229,1998-09-30,0.6651080397960565
Journal of Organic Chemistry,Total Synthesis of Olivacine and Ellipticine via a Lactone Ring-Opening and Aromatization Cascade,"Effective preparation of olivacine and ellipticine via late-stage D-ring cyclization is described. Key features of the synthetic routes include trifluoroacetic acid-mediated formation of a lactone that is fused to a tetrahydrocarbazole derivative and its one-pot two-step ring opening and aromatization mediated by para-toluenesulfonic acid and palladium on carbon, respectively.",10.1021/acs.joc.9b00706,2019-05-22,0.6651043139886393
Organic Letters,Enantioselective Synthesis of an HCV NS5a Antagonist,"A concise, enantioselective synthesis of the HCV NS5a inhibitor MK-8742 (1) is reported. The features of the synthesis include a highly enantioselective transfer hydrogenation of an NH imine and a dynamic diastereoselective transformation. The synthesis of this complex target requires simple starting materials and nine linear steps for completion.",10.1021/ol500971c,2014-04-11,0.6650678867632245
Angewandte Chemie International Edition,Enantioselective Synthesis of (−)‐Halenaquinone,"The efficient, 12-14 step (LLS) total synthesis of (-)-halenaquinone has been achieved. Key steps in the synthetic sequence include: (a) proline sulfonamide-catalyzed, Yamada-Otani reaction to establish the C6 all-carbon quaternary stereocenter, (b) multiple, novel palladium-mediated oxidative cyclizations to introduce the furan moiety, and (c) oxidative Bergman cyclization to form the final quinone ring.",10.1002/anie.201805370,2018-06-19,0.6650281555991601
Journal of the American Chemical Society,"Total Synthesis of (−)-Nodulisporic Acids D, C, and B: Evolution of a Unified Synthetic Strategy","A unified synthetic strategy leading to the total synthesis of (-)-nodulisporic acids D, C, and B is described. Key synthetic transformations include a nickel-chromium-mediated cyclization, an aromatic ring functionalization employing a novel copper-promoted alkylation, a palladium-catalyzed cross-coupling cascade/indole ring construction, and a palladium-mediated regio- and diastereoselective allylic substitution/cyclization reaction, the latter to construct ring D.",10.1021/jacs.8b04053,2018-07-20,0.6650242583676749
Organic Letters,Pyridone Annulation via Tandem Curtius Rearrangement/6π-Electrocyclization: Total Synthesis of (−)-Lyconadin C,"A concise, enantioselective total synthesis of the Lycopodium alkaloid (-)-lyconadin C was achieved in 12 steps and high overall yield. Key features include construction of a luciduline congener through Mannich-type cyclization and a one-pot, tandem Curtius rearrangement/6π-electrocyclization to fashion the 2-pyridone system of lyconadin C.",10.1021/ol401954f,2013-08-02,0.6650186383606528
Synthesis,"Chemoenzymatic Enantioselective Synthesis of the Hancock Alkaloids (S)- and (R)-Galipeine, (S)-Cuspareine, (S)-Galipinine, and (S)-Angustureine","Abstract The enantioselective synthesis of the Hancock 1,2,3,4-tetrahydroquinoline alkaloids (S)-galipeine, (S)-cuspareine, (S)-galipinine, and (S)-angustureine and the nonnatural enantiomer (R)-galipeine is described herein. The target compounds were obtained in five steps from a racemic quinaldinic acid derived α-amino ester in overall yields of 21.2% to 37.5%. The synthetic route comprised two key steps: an enzymatic kinetic resolution to control the C-2 stereocenter, affording (R)- and (S)-α-amino esters as key chiral intermediates with 94% and 72% ee, respectively, and Wittig olefination of (R)- and (S)-α-amino aldehyde synthons with the corresponding phosphonium salts using a phase-transfer system (t-BuOH/CH2Cl2), thereby allowing the introduction of alkyl substituents at C-2. Finally, the enantioselective synthesis was concluded with the catalytic hydrogenation of olefinic bonds on the Wittig adducts to furnish the target Hancock alkaloids, including (R)-galipeine, whose synthesis is described here for the first time.",10.1055/a-1984-9689,2022-11-23,0.6649645362191817
Organic Letters,Total Synthesis of (−)-Apicularen A,"A convergent total synthesis of (-)-apicularen A, a highly cytostatic 12-membered macrolide, has been accomplished. The key steps include assembling of iodoalkene 8 and aldehyde 9 by Nozaki-Hiyama-Kishi (NHK) coupling, stereospecific construction of 2,6-trans-disubstituted dihydropyran by Pd(II)-catalyzed 1,3-chirality transfer reaction, and Yamaguchi macrolactonization. Introduction of the (2Z,4Z)-heptadienamide moiety in the side chain by an efficient Cu(I)-mediated coupling completed the total synthesis.",10.1021/ol101753y,2010-08-13,0.6649633210692422
Journal of Organic Chemistry,Synthesis of (±)-Aureol by Bioinspired Rearrangements,"A bioinspired and sustainable procedure for the straightforward synthesis of (±)-aureol has been achieved in eight steps (14% overall yield) from epoxyfarnesol. The key steps are the titanocene(III)-catalyzed radical cascade cyclization of an epoxyfarnesol derivative and a biosynthetically inspired sequence of 1,2-hydride and methyl shifts.",10.1021/jo502841u,2015-01-15,0.664892941979479
Synlett,Synthesis of (±)-1-Phenyl-2-azabicyclo[2.2.1]heptane Derivatives - Novel NK<sub>1</sub>Receptor Ligands,"The synthesis of the 1-phenyl-2-azabicyclo[2.2.1]heptane derivative 2, a potential NK1 receptor ligand, is reported. Ring-closing metathesis of diene 10 and regio- and stereoselective opening of the oxirane ring in 14 are key steps in the synthetic sequence.",10.1055/s-2006-926221,2006-01-01,0.6648925271569719
Angewandte Chemie International Edition,"Concise and Enantioselective Total Synthesis of (−)‐Mehranine, (−)‐Methylenebismehranine, and Related <i>Aspidosperma</i> Alkaloids","We report an efficient and highly stereoselective strategy for the synthesis of Aspidosperma alkaloids based on the transannular cyclization of a chiral lactam precursor. Three new stereocenters are formed in this key step with excellent diastereoselectivity due to the conformational bias of the cyclization precursor, leading to a versatile pentacyclic intermediate. A subsequent stereoselective epoxidation followed by a mild formamide reduction enabled the first total synthesis of the Aspidosperma alkaloids (-)-mehranine and (+)-(6S,7S)-dihydroxy-N-methylaspidospermidine. A late-stage dimerization of (-)-mehranine mediated by scandium trifluoromethanesulfonate completed the first total synthesis of (-)-methylenebismehranine.",10.1002/anie.201405609,2014-09-04,0.6648897039564478
Organic Process Research & Development,"Development of a Large-Scale Stereoselective Process for (1<i>R</i>,4<i>S</i>)-4-(3,4-Dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-amine Hydrochloride","A convenient, multikilogram-scale, stereoselective process for the synthesis of (1 R,4 S )-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydronaphthalen-1-amine hydrochloride 1 is described. The key steps involve synthesis of sulfinyl imine ( R s, 4 S )-5 from ( S )-tetralone (4 S )-3 and ( R )- tert -butylsulfinamide ( R s )-4, and its stereoselective reduction with 9-BBN to produce the (1 R )-amine center of 1 . The process has been scaled up to multikilogram scale and gives 1 in an overall yield of >50% with a chemical purity of 99.7 A% by HPLC and stereochemical purity of >99.9% by chiral HPLC.",10.1021/op7000589,2007-06-20,0.6648851661320583
Organic Letters,"Synthesis of the (3<i>R</i>,6<i>S</i>)-3-Amino-6-(2,3-difluorophenyl)azepan-2-one of Telcagepant (MK-0974), a Calcitonin Gene-Related Peptide Receptor Antagonist for the Treatment of Migraine Headache","Two novel routes have been developed to the (3 R,6 S)-3-amino-6-(2,3-difluorophenyl)-1-(2,2,2-trifluoroethyl)azepan-2-one 2 of the CGRP receptor antagonist clinical candidate telcagepant (MK-0974, 1). The first employs a ring-closing metathesis of the styrene 7 as the key reaction, while the second makes use of a highly diastereoselective Hayashi-Miyaura Rh-catalyzed arylboronic acid addition to nitroalkene 16. The latter route has been implemented to produce multigram quantities of telcagepant for extensive preclinical evaluation.",10.1021/ol8011524,2008-07-01,0.6648472684103741
Synthesis,"An Enantiospecific Route to (+)-(1R,3S)-cis-Chrysanthemic Acid from (-)-d-Pantolactone¹","In this paper, a novel route for the synthesis of (+)-(1R,3S)-cis-chrysanthemic acid is described. The use of readily available (-)-d-pantolactone as a starting point, application of ring-closing metathesis to form the cyclopentene intermediate, and Haller-Bauer/Grob-type fragmentation to form the target compound are the highlights of the present synthesis.",10.1055/s-0030-1258451,2011-03-01,0.6648360441837726
Angewandte Chemie International Edition,Rhodium‐Catalyzed Desymmetrization by Hydroformylation of Cyclopentenes: Synthesis of Chiral Carbocyclic Nucleosides,"Excellent enantioselectivities (up to 97 % ee) and diastereoselectivities (up to >99:1 d.r.) have been achieved in the desymmetrization of cyclopentenes by catalytic hydroformylation. This novel methodology provides an efficient and concise synthetic route to chiral cyclopentane carboxaldehydes. The key intermediate, (1S,3S)-(3-hydroxymethyl)cyclopentanol, for the synthesis of carbocyclic-ddA was obtained in three steps.",10.1002/anie.201601478,2016-04-18,0.6648206247319459
Tetrahedron,"Total synthesis of thiangazole, a novel inhibitor of HIV-1 from polyangium sp",,10.1016/s0040-4039(00)77284-4,1994-08-01,0.6647876811048637
Tetrahedron,"A new synthesis, including asymmetric synthesis, of alkylidenecyclopropanes by 1,2-CC insertion of cyclobutylmagnesium carbenoides as the key reaction",,10.1016/j.tetlet.2009.04.038,2009-04-15,0.6647597886207025
Journal of Organic Chemistry,"Asymmetric Total Synthesis of (−)-Spirochensilide A, Part 1: Diastereoselective Synthesis of the ABCD Ring and Stereoselective Total Synthesis of 13(<i>R</i>)-Demethyl Spirochensilide A","A concise and diastereoselective construction of the ABCD ring system of spirochensilide A is described. The key steps of this synthesis are a semipinacol rearrangement reaction to stereoselectively construct the AB ring system bearing two vicinal quaternary chiral centers and a Co-mediated Pauson–Khand reaction to form the spiro-based bicyclic CD ring system. This chemistry leads to the stereoselective synthesis of 13( R )-demethyl spirochensilide A, paving the way for the first asymmetric total synthesis of (−)-spirochensilide A.",10.1021/acs.joc.0c02494,2021-01-12,0.6647585573077708
Journal of the American Chemical Society,Total Synthesis of Amphidinolide X,"A concise total synthesis of the cytotoxic marine natural product amphidinolide X (1) is described. A key step of the highly convergent route to this structurally rather unusual macrodiolide derivative consists of a newly developed, highly syn selective formation of allenol 6 by an iron-catalyzed ring opening reaction of the enantioenriched propargyl epoxide 5 (derived from a Sharpless epoxidation) with a Grignard reagent. Allenol 6 was then cyclized with the aid of Ag(I) to give dihydrofuran 7 containing the (R)-configured quarternary sp3 chiral center at C19 of the target. The anti-configured chiral centers at C10 and C11 were formed by the palladium-catalyzed, Et2Zn-promoted addition of propargyl mesylate 12 to the functionalized aldehyde 11. The key fragment coupling at the C13-C14 bond was achieved by the ""9-MeO-9-BBN"" variant of the alkyl-Suzuki reaction. Finally, the 16-membered macrodiolide ring was formed by a Yamaguchi esterification/lactonization strategy.",10.1021/ja044130+,2004-11-19,0.6646690447390912
Angewandte Chemie International Edition,Total Synthesis of (−)-Mucocin,"A highly convergent, modular strategy for the total synthesis of the annonaceous acetogenin (-)-mucocin is reported. The remarkable features are the endo-selective formation of the tetrahydropyran ring from an activated epoxide and the stability of the butenolide in the coupling with an organomagnesium compound.",10.1002/(sici)1521-3773(19990503)38:9<1263::aid-anie1263>3.0.co;2-2,1999-05-03,0.6646635057642986
Tetrahedron,"Stereoselective synthesis of (2,4)-dien-1-ols; key intermidiates for synthesis of sex pheromones of silk worm and of grape vine moth",,10.1016/s0040-4039(01)80994-1,1987-01-01,0.6646525952857328
Journal of Organic Chemistry,Synthesis of 4-Acetylisocoumarin:  First Total Syntheses of AGI-7 and Sescandelin,"A practical synthetic route to 4-acetylisocoumarins and the first total synthesis of AGI-7 (5) and sescandelin (4) are described. The readily available homophthalate 8 was transformed to the vinylogous amide ester 13 in high overall yield. Upon treatment of 13 with refluxing aqueous formic acid, the desired 4-acetylisocoumarin (5) and its regioisomer 3-methyl-4-formylisocoumarin (17) were produced in a 3:1 ratio. After separation of the desired product (5) from the unwanted minor isomer, the enantioselective reduction of AGI-7 by borane in the presence of Corey's (S)-oxazaborolidine reagent afforded (+)-sescandelin (4) with a 93% ee.",10.1021/jo010789b,2002-03-29,0.6646251191600484
Organic Process Research & Development,"Regioselective Epoxide Ring Opening for the Stereospecific Scale-Up Synthesis of BMS-960, A Potent and Selective Isoxazole-Containing S1P<sub>1</sub> Receptor Agonist","This article presents a stereospecific scale-up synthesis of ( S )-1-(( S )-2-hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperidine-3-carboxylic acid (BMS-960), a potent and selective isoxazole-containing S1P 1 receptor agonist. The process highlights an enzymatic reduction of α-bromoketone toward the preparation of ( S )-bromo alcohol, a key precursor of ( S )-4-(oxiran-2-yl)benzonitrile. A regioselective and stereospecific epoxide ring-opening reaction was also optimized along with improvements to 1,2,4-oxadiazole formation, hydrolysis, and crystallization. The improved process was utilized to synthesize batches of BMS-960 for Ames testing and other toxicological studies.",10.1021/acs.oprd.6b00366,2017-01-12,0.6645949895542161
Tetrahedron,A new strategy for dinucleotide synthesis via phosphite route involving phosphorochloridates as intermediates,,10.1016/s0040-4039(00)95534-5,1987-01-01,0.6645945313825976
Organic Process Research & Development,Development of a Robust and Scalable Process for the Large-Scale Preparation of Vadadustat,"A novel and scalable process is developed for the industrial synthesis of vadadustat. The four-step process is one step shorter compared to the reported routes with an increase in total yield to 49.1%. Detailed optimizations furnish vadadustat with a purity of >99.5% through cross-coupling, aromatic substitution and nitrile hydrolysis, amidation, and ester-ether deprotection. The process is also robust and was demonstrated in a kilogram laboratory. Meanwhile, the corresponding impurity profile was thus studied in detail and well documented.",10.1021/acs.oprd.1c00004,2021-03-05,0.6645830151132959
Tetrahedron,"Generation of alkylidene carbenes from α,β-epoxy-N-aziridinyl imines. A new route to cyclopentenols",,10.1016/s0040-4039(00)74418-2,1994-11-01,0.6645819810947552
Organic Process Research & Development,"Development of a Multigram Synthesis of URB937, a Peripherally Restricted FAAH Inhibitor","A new synthetic approach to URB937 was developed starting from the inexpensive and widely available 4-benzyloxyphenol. A reproducible four-step procedure, requiring no chromatographic purifications, was optimized that allowed the preparation of 100 g of URB937 in 45% overall yield.",10.1021/op300301u,2013-02-05,0.6645640572045469
Journal of the American Chemical Society,The Total Synthesis of (±)-Merrilactone A,"The total synthesis of the title compound has been accomplished in 20 steps. The key step is a free radical cyclization of vinyl bromide 29 to afford 30. The synthesis also features an efficient Dielsminus signAlder reaction of 2,3-dimethylmaleic anhydride with 1-(tert-butyldimethylsiloxy)-butadiene. The oxetane moiety of merrilactone A is fashioned via a Payne-like rearrangement of a hydroxyepoxide (see 2 right arrow 1).",10.1021/ja012495d,2002-02-16,0.6645482533667125
Synlett,"Enantioselective Synthesis of (+)-(<i>S</i>,<i>S</i>)-Reboxetine","An efficient enantioselective synthesis leading directly to (+)-(S,S)-reboxetine has been described from commercially available trans-cinnammyl bromide using Sharpless asymmetric dihydroxylation as the key step.",10.1055/s-2006-944210,2006-07-01,0.6644580565103868
Tetrahedron,"Practical, high-yield synthesis of thiol-terminated diacetylenes for formation of conductive monolayers",,10.1016/j.tetlet.2018.08.057,2018-08-29,0.6644514292333518
Synthesis,A Novel Method for the Introduction of Fluorine into the Purine 2-Position: Synthesis of 2-Fluoroadenosine and a Formal Synthesis of the Antileukemic Drug Fludarabine,A novel method for the introduction of fluorine in the purine 2-position is described and employed in the synthesis of a potential antimycobacterial compound. Also 2-fluoroadenosine has been synthesized for the first time from adenosine with perbenzo­ylated 2-nitroadenosine as a key intermediate. Mild reaction conditions are employed and few synthetic steps are required. The novel synthesis of fluoroadenosine can be regarded as a formal synthesis of the antileukemic drug fludarabine phosphate.,10.1055/s-2006-942544,2006-08-02,0.6644500084950861
Organic Letters,"Synthesis of <i>Adagrasib</i> (MRTX849), a Covalent KRAS<sup>G12C</sup> Inhibitor Drug for the Treatment of Cancer","High Resolution Image Download MS PowerPoint Slide A concise, transition-metal and protection-free synthesis of adagrasib (MRTX849), a novel KRAS G12C inhibitor drug recently approved by the FDA, is reported. Introduction of two chiral building blocks to the tetrahydropyridopyrimidine core was accomplished via two sequential S N Ar reactions. Extensive reaction optimization led to a robust, transition-metal-free oxidation of the sulfide intermediate. A judicious choice of the leaving group with favorable steric and electronic characteristics at the 4-OH position of the tetrahydropyridopyrimidine core enabled a facile S N Ar displacement to introduce the chiral piperazine. This new, five-step, chromatography-free synthesis of adagrasib from readily available starting materials obviated the palladium catalysis and protecting group manipulations in the current commercial route and significantly improved the efficiency of the process in 45% overall yield.",10.1021/acs.orglett.2c04266,2023-02-01,0.6644342906085376
European Journal of Organic Chemistry,"Diastereoselective Entry to Novel Aminoindolizidines with Fused Furan, Thiophene, and Pyrrole Ring Starting from <i>L</i>‐Glutamic Acid","Abstract A series of novel optically pure aminoindolizidines featuring fused tetrahydro‐furan, thiophene, or pyrrole ring were synthesized from the proteinogenic L ‐glutamic acid as a chiral precursor and a nitrogen atom source. The synthetic sequence employed tricyclic indolizidinols as advanced building blocks, which were prepared on a gram‐scale from bioavailable reagents. Key transformations within the used synthetic sequence included diastereoselective Thompson azidation, Staudinger reduction, Jurjew reaction, and highly diastereoselective catalytic hydrogenation. These steps facilitated the efficient and stereoselective synthesis of the ultimate amino‐ and N ‐acetylamino‐indolizidines.",10.1002/ejoc.202401219,2025-01-01,0.6644007413354569
Tetrahedron,"Synthesis of 5,6-difluoroarachidonic acid, a potential inhibitor of 5-lipoxygenase",,10.1016/0040-4039(96)00976-8,1996-07-01,0.6643998101639347
Organic Process Research & Development,Effective Laboratory-Scale Preparation of Axitinib by Two CuI-Catalyzed Coupling Reactions,"The discovery and development of an efficient synthesis route to axinitib is reported. The first-generation route researched by Pfizer implemented two Pd-catalyzed coupling reactions as key steps. In this work, the development of Heck-type and C–S coupling reactions catalyzed by CuI is briefly described, using an economial and practical protocol. Aspects of this route, such as selecting optimal ligands, solvent, and other conditions, are discussed in detail. The scale-up experiment was carried out to provide more than 300 g of active pharmaceutical ingredients of axitinib in Form XLI with 99.9% purity in 39% yield. In short, we provide a new choice of synthesis route to axitinib, through two copper-catalyzed coupling reactions with good yield.",10.1021/acs.oprd.5b00123,2015-06-11,0.664394180024732
Synthesis,Convergent Total Synthesis of (±)-Apomorphine via Benzyne Chemistry: Insights into the Mechanisms Involved in the Key Step,"Convergent total synthesis of (±)-apomorphine hydrochloride was accomplished by an approach that employs in the key step a sequence of transformations involving a [4+2]-cycloaddition reaction followed by a hydrogen migration. Through this sequence of transformations, the desired aporphine core was obtained regioselectively in 75% isolated yield. Since only one regioisomer was produced in the key step of the synthesis, a polar [4+2]-cycloaddition mechanism was proposed. Furthermore, NMR experiments and theoretical calculations were carried out to elucidate the hydrogen migration mechanism. (±)-Apomorphine hydrochloride was achieved after 9 steps in an overall yield of 8% involving benzyne chemistry.",10.1055/s-0036-1588855,2017-06-20,0.6643914200857419
Synthesis,Diversity-Oriented Synthesis of Aminocyclohexitols from Garner's Aldehyde,"A short and efficient synthetic route to three stereoisomeric aminocyclohexane tetrols of the quercitol type has been developed from l -serine, which featured stereoselective allylation, stereocontrolled dihydroxylation, and ring-closing metathesis as key steps.",10.1055/s-0032-1317962,2013-01-09,0.6643384095411113
Tetrahedron,"A new synthetic route to N, O, bis-dimethylphenylsilyl amino acid",,10.1016/s0040-4039(00)91457-6,1975-01-01,0.6643369553211284
Angewandte Chemie International Edition,Total Synthesis of (−)‐13‐Oxyingenol and its Natural Derivative,"Ring functionalization: the total synthesis of a natural derivative of (-)-13-oxyingenol, a potent anti-HIV diterpenoid, is reported. The key steps in this synthesis include a ring-closing olefin metathesis and a Mislow-Evans-type [2,3]-sigmatropic rearrangement. This synthesis provides access to (-)-13-oxyingenol and its natural derivative in 21 steps from a synthetic intermediate previously prepared by Kigoshi and co-workers.",10.1002/anie.201201383,2012-04-05,0.664327284187617
Tetrahedron,A simple convergent synthesis of the mannosidase inhibitor 1-deoxymannonojirimycin for sucrose,,10.1016/0040-4039(92)88046-8,1992-01-01,0.664322569375694
Organic Process Research & Development,Process Development and Scale-up for (±)-Reboxetine Mesylate,"Redevelopment of the commercial process for the synthesis of (±)-reboxetine methanesulfonate is described. An optimized and efficient process for the synthesis of (±)-reboxetine starting from cinnamyl alcohol was developed. The redeveloped process minimizes impurity formation and utilizes simplified processing to substantially improve process yield and throughput, and is suitable for the efficient synthesis of multiton quantities of reboxetine.",10.1021/op7000063,2007-03-23,0.6643106740228164
Organic Letters,Concise Total Synthesis of (−)-Muricatacin by Tandem Ring-Closing/Cross Metathesis,"A strategy for the synthesis of chiral 5-(1-hydroxyalk-2-enyl)-5H-furan-2-ones and its application to the total synthesis of (-)-muricatacin, in four steps and 37% overall yield from (R,R)-hexa-1,5-diene-3,4-diol, are described. The key synthetic step in this approach is a highly regioselective and stereoselective tandem ring-closing/cross metathesis reaction in which both lactone formation and alkyl chain extension are accomplished in an efficient one-pot process.",10.1021/ol040047f,2004-10-12,0.6642965707005253
Journal of the American Chemical Society,"Asymmetric Total Synthesis of Arcutinidine, Arcutinine, and Arcutine","We have accomplished the asymmetric total synthesis of arcutinidine, arcutinine, and arcutine, three arcutine-type C20-diterpenoid alkaloids. A pentacyclic intermediate was rapidly assembled by using two Diels–Alder reactions. We developed a cascade sequence of Prins cyclization and Wagner–Meerwein rearrangement to construct the core of arcutinidine, which was then elaborated into an oxygenated pentacycle through a scalable route. Chemoselective reductive amination followed by spontaneous imine formation furnished the pyrroline motif in the final stage. We clarified the S configuration of the α-carbon of the acyl group within arcutine through chemical synthesis and crystallographic analysis.",10.1021/jacs.9b05818,2019-07-05,0.6642648304534193
Organic Letters,Total Synthesis of (+)-Pancratistatin and Its Potent Topo I Inhibition Activity Studies,"As a preeminent anticancer natural product, (+)-pancratistatin has always been a privileged synthetic target. Herein, the total synthesis of (+)-pancratistatin is reported in 10 linear steps by utilizing a known aldehyde as chiral source. This synthetic route features a highly stereoselective intermolecular Michael addition and intramolecular Henry reaction to construct a cyclohexane ring bearing 6 successive stereocenters. Moreover, all of the synthetic steps are reliable and efficient and can be easily scaled up, which facilitated anticancer pharmacological tests of (+)-pancratistatin. Importantly, a new pharmacological mechanism of action was discovered for the first time where (+)-pancratistatin is able to inhibit the activity of topoisomerase I, which would pave the way for the development of new-type Topo I inhibitors.",10.1021/acs.orglett.2c03888,2022-12-15,0.6642353601892649
Journal of Organic Chemistry,Synthesis of Kainoids and C4 Derivatives,"A unified stereoselective synthesis of 4-substituted kainoids is reported. Four kainic acid analogues were obtained in 8–11 steps with up to 54% overall yields. Starting from trans -4-hydroxy- l -proline, the sequence enables a late-stage modification of C4 substituents with sp 2 nucleophiles. Stereoselective steps include a cerium-promoted nucleophilic addition and a palladium-catalyzed reduction. A 10-step route to acid 21a was also established to enable ready functionalization of the C4 position.",10.1021/acs.joc.8b00179,2018-05-08,0.6641628836423337
European Journal of Organic Chemistry,A Convenient Route for the Synthesis of 3‐Deazaspongosine,"Abstract The first chemical synthesis of the 3‐deazaspongosine nucleoside is described, starting from commercially available 4‐amino‐2,6‐dichloropyridine. The key step is the introduction of required functional groups at the 2 and 6 positions of the 4‐amino‐3‐nitropyridine without any conflict in the synthesis of nucleobase. Regioselective nucleophilic substitution with allyl alkoxide at the 2 position of 4‐amino‐2,6‐dimethoxypyridine, followed by sequential deallylation and chlorination led to the desired 2‐chloro derivative. Ring closure of the 3,4‐diaminopyridine and stereoselective glycosylation of the imidazo[4,5‐ c ]pyridine with tetraacetate‐protected ribofuranose gave only the N 9 ‐β‐isomer. A final nucleophilic displacement of the 6‐chloride by hydrazine followed by reduction with Raney Nickel gave the desired 3‐deazaspongosine.",10.1002/ejoc.201301283,2013-11-22,0.6641513436836333
Organic Process Research & Development,A Concise Synthesis of a Tetrahydropyrazolopyrazine Building Block,"A concise synthesis of a tetrahydropyrazolopyrazine building block is described. 5-Methyl-4,5,6,7-tetrahydropyrazolo[1,5- a ]pyrazin-2-ylamine was prepared in three steps and 80% yield from 5-nitro-2 H -pyrazole-3-carboxylic acid. This compound was then coupled with 4-bromo-6-chloro-2-methyl-2 H -pyridazin-3-one in the presence of sodium tert -pentoxide to give the target product in 87% yield. The process was successfully scaled up to a multihundred gram scale.",10.1021/op300270r,2012-10-26,0.6641506243986102
Tetrahedron,"An improved synthesis of 14α-hydroxy-15,16-dehydro-17-oxomarcfortine A; A key intermediate in the synthesis of 14α-hydroxymarcfortine A",,10.1016/s0040-4039(97)00821-6,1997-06-01,0.6640784526277892
Journal of Organic Chemistry,Asymmetric Synthesis of Triazole Antifungal Agents Enabled by an Upgraded Strategy for the Key Epoxide Intermediate,"A streamlined and efficient approach to the key epoxide intermediate for the asymmetric synthesis of triazole antifungal agents is presented. This synthesis highlights a P(NMe 2 ) 3 -mediated nonylidic olefination of α-keto ester, ensuring the exclusive formation of the requisite ( Z )-alkene, followed by a highly enantioselective Jacobsen epoxidation to establish the two vicinal stereocenters in a single step. The versatility of this strategy is exemplified through the efficient synthesis of efinaconazole and ravuconazole.",10.1021/acs.joc.4c00193,2024-03-21,0.6640534207133143
Synthesis,First Total Synthesis of 5-Hydroxy-3-methyl-4-propylsulfanyl-5H-furan-2-one: A Cancer Chemopreventive Agent,"The first total synthesis of 5-hydroxy-3-methyl-4-propylsulfanyl-5H-furan-2-one, a newly discovered natural product with anticancer property is described by two different routes. A sequence involving an incorporation of a methyl group via a Gilman reagent and a chemoselective reduction of a cyclic anhydride functionality are the key steps. The methods proposed start from easily available starting materials and allow ready preparation of the final compound in good overall yield.",10.1055/s-0030-1260004,2011-04-15,0.6640232676509564
Journal of Organic Chemistry,"New, Azide-Free Transformation of Epoxides into 1,2-Diamino Compounds:  Synthesis of the Anti-Influenza Neuraminidase Inhibitor Oseltamivir Phosphate (Tamiflu)","A new, azide-free transformation of the key precursor epoxide 6 to the influenza neuraminidase inhibitor prodrug oseltamivir phosphate (1, Tamiflu) is described. This sequence represents a new and efficient transformation of an epoxide into a 1,2-diamino compound devoid of potentially toxic and hazardous azide reagents and intermediates and avoids reduction and hydrogenation conditions. Using catalytic MgBr(2).OEt(2) as a new, inexpensive Lewis acid, the introduction of the first amino function was accomplished by opening of the oxirane ring with allylamine followed by Pd/C-catalyzed deallylation to the amino alcohol 16. The introduction of the second amino group was then accomplished via an efficient reaction cascade involving a domino sequence preferably utilizing a transient imino protection. Selective acetylation of the resulting diamine 17 was achieved under acidic conditions providing the crystalline 4-acetamido-5-N-allylamino-derivative 18, which upon deallylation over Pd/C and phosphate salt formation afforded drug substance 1. The overall yield of this route from 6 of 35-38% exceeds the yield of the azide-based process (27-29%) and does not require any chromatographic purification.",10.1021/jo005702l,2001-02-24,0.6640054650891306
Angewandte Chemie International Edition,Chemoenzymatic Synthesis of Advanced Intermediates for Formal Total Syntheses of Tetrodotoxin,"Advanced intermediates for the syntheses of tetrodotoxin reported by the groups of Fukuyama, Alonso, and Sato were prepared. Key steps include the toluene dioxygenase mediated dihydroxylation of either iodobenzene or benzyl acetate. The resulting diene diols were transformed into Fukuyama's intermediate in six steps, into Alonso's intermediate in nine steps, and into Sato's intermediate in ten steps.",10.1002/anie.201804602,2018-05-11,0.6639795823378808
Organic Process Research & Development,"Development of a Scalable Synthesis toward a KRAS G12C Inhibitor Building Block Bearing an All-Carbon Quaternary Stereocenter, Part 1: From Discovery Route to Kilogram-Scale Production","Synthesis of molecules containing all-carbon quaternary stereocenters has been a longstanding challenge in organic chemistry. In one of our discovery oncology programs, a key chiral building block bearing an all-carbon quaternary chiral center was of particular interest and was later identified as a core structure for a KRAS G12C inhibitor. Herein, the development of a safer and practical route to the key building block 1 is described. By replacing processes involving the use of an energetic reagent and extensive chromatographic purifications, a scalable process utilizing chemical resolution was developed to access the chiral building block in kilogram quantities, enabling timely delivery of API for preclinical and clinical studies.",10.1021/acs.oprd.3c00362,2024-01-04,0.663976380906565
European Journal of Organic Chemistry,Studies towards the Total Synthesis of Drimentine C. Preparation of the AB and CDEF Ring Fragments,"bacteria. Members of this family display weak antitumor and antibacterial activity. Herein we report our efforts toward the total synthesis of drimentine C using three distinct approaches incorporating palladium-catalyzed cyanoamidation, reductive cross-coupling, and photoredox-catalyzed α-alkylation of an aldehyde as key steps. Our synthetic efforts use a convergent synthesis to assemble the terpenoid and alkaloid portions of drimentine C from readily available l-tryptophan, l-proline, and (+)-sclareolide.",10.1002/ejoc.202000158,2020-03-19,0.6639725398520487
Synlett,First Diastereoselective Synthesis of (-)-Thyrsiflorin A Methyl Ester,"All articles of this category The diastereoselective synthesis of the simplest member of the scopadulan diterpenes, (-)-thyrsiflorin A methyl ester 10 from chiral (+)-podocarp-8(14)-en-13-one 1 , of known absolute configuration, is described. A key step in our synthesis is the intramolecular cyclopropanation of the diazoketone 5 and subsequent regioselective cleavage of the cyclopropane ring. diastereoselective synthesis - Scopadulan diterpenes - cyclopropane cleavage - podocarpenone",10.1055/s-1997-3217,1997-05-01,0.6639163673819529
Organic Letters,Assembly of the Tricyclic Core of Alopecurone C by Asymmetric Donor/Donor Carbene C–H Insertion,"Two routes to assemble the complete tricyclic core of alopecurone C are described. In the first-generation route, an efficient synthesis of the ""eastern"" half of the target, including a decagram-scale rhodium-catalyzed C-H insertion reaction, was developed. When this route proved intractable for assembling the final flavanone ring, a successful second-generation route was developed from a flavanone precursor (naringenin) employing a later stage C-H insertion. Although the second route was ultimately unsuccessful for preparation of the final target, it does provide the basis for the efficient assembly of the complete tricyclic core of alopecurone C and related flavonostilbenoid natural products.",10.1021/acs.orglett.4c03863,2024-12-12,0.6638611915099877
Tetrahedron,A convergent synthesis of the renin inhibitor SPP-100 using a nitrone intermediate,,10.1016/s0040-4039(01)00883-8,2001-07-01,0.6638605420759542
Journal of Organic Chemistry,Total Synthesis of 20-Norsalvinorin A. 1. Preparation of a Key Intermediate,"The key tricyclic intermediate 3a, for the total synthesis of the C(20)-nor analogue of salvinorin A, was prepared in seven steps from 3-furaldehyde. Key steps involved a highly regio- and diastereoselective Lewis acid assisted Diels-Alder reaction followed by base-promoted epimerization and a completely stereoselective conjugate reduction.",10.1021/jo802623n,2009-02-20,0.6638519404222826
Tetrahedron,Total synthesis of a new topoisomerase II inhibitor BE 10988,,10.1016/s0040-4039(00)79232-x,1993-06-01,0.6638505879103591
Angewandte Chemie International Edition,Regio‐ and Stereocontrolled Total Synthesis of Benanomicin B,"Fully controlled total synthesis of benanomicin B was achieved by exploiting two key steps: a stereocontrolled ring-opening of a lactone (see scheme, step A), and a semipinacol cyclization of an acetal-aldehyde derivative discriminating the two hydroxy groups of the pseudo-C2-symmetric 1,2-diol moiety (step B).",10.1002/anie.200501210,2005-05-18,0.6638331256733001
Organic Process Research & Development,"An Efficient Approach to 3-Bromo-6-chloro-phenanthrene-9,10-dione","A practical and efficient synthesis of 3-bromo-6-chloro-phenanthrene-9,10-dione was developed and demonstrated on a large scale. The synthetic approach involves six chemical steps and two isolations in 73% overall yield. The key transformations feature an anionic cyclization for generation of the phenanthrene ring, followed by sequential tribromination and hydrolysis for the incorporation of the bromo-diketone functionality.",10.1021/op8001678,2008-09-13,0.6638244454398828
Organic Process Research & Development,An Efficient and Practical Synthesis of the HIV Protease Inhibitor Atazanavir via a Highly Diastereoselective Reduction Approach,"An efficient and practical synthesis of the HIV-1 protease inhibitor Atazanavir was developed by employing the diastereoselective reduction of ketomethylene aza-dipeptide isostere 10 as the key and final step. The high diastereoselectivity of the amino ketone reduction by lithium tri- tert -butoxyaluminum hydride in diethyl ether to afford the desired syn -1,2-amino alcohol structure was achieved by Felkin−Anh control as a result of the bulky and chiral N -(methoxycarbonyl)- l - tert -leucinyl moiety as the nitrogen protecting group. The coupling of the two key intermediates, N -(methoxycarbonyl)- l - tert -leucine acylated benzyl hydrazine 7 and chloromethyl ketone 9, via an S N 2 reaction furnished the amino ketone 10 in high yield under our optimized conditions. Our new methodology features the late introduction of the S -hydroxyl group and the early acylation of benzyl hydrazine and chloromethyl ketone with N -(methoxycarbonyl)- l - tert -leucine, respectively, which confers high efficiency and easy purification.",10.1021/op7001563,2008-01-01,0.6637921090487641
Organic Process Research & Development,Development of a Large-Scale Synthetic Route to Manufacture (−)-Huperzine A,"A safe, practical and scalable process for manufacture of (−)-huperzine A has been developed and scaled up to manufacture several hundred grams of (−)-huperzine A with chemical and optical purity of >99%. The process consists of 11 chemical stages starting from commercially available materials with only nine isolation steps and no chromatography purification. This process provides a reliable and cost-effective source of synthetic (−)-huperzine A and its derivatives for pharmaceutical and nutraceutical markets.",10.1021/op200360b,2012-03-01,0.6637902170735112
Tetrahedron,"A route for the enantioselective total synthesis of antheridic acid, the antheridium-inducing factor from anemia phyllitidis",,10.1016/s0040-4039(00)93418-x,1991-09-01,0.6637753521670903
Angewandte Chemie International Edition,"Contractive Annulation: A Strategy for the Synthesis of Small, Strained Cyclophanes and Its Application in the Synthesis of [2](6,1)Naphthaleno[1]paracyclophane","A new synthetic strategy (contractive annulation) for the synthesis of highly strained cyclophanes has been conceived and its viability has been demonstrated through a nine-step synthesis of [2](6,1)naphthaleno[1]paracyclophane from [2.2]paracyclophane.",10.1002/anie.201904673,2019-05-10,0.6637577297573276
Organic Letters,Total Synthesis of Proteasome Inhibitor (−)-Omuralide through Asymmetric Ketene [2 + 2]-Cycloaddition,"The total synthesis of (-)-omuralide, a potent specific proteasome inhibitor, has been achieved through an unprecedented route. The C3 and C4 chiral centers of the natural product have been selectively installed by an asymmetric [2 + 2]-cycloaddition between an unusual oxadisilinane ketene and a chiral enol ether, while the γ-lactam core was prepared by a single-pot two-step Beckmann transposition. The C5 quaternary center was eventually defined by an original selective oxidative desymmetrization of a spiro cyclic oxadisilinane thanks to the anchimeric assistance of a proximal hydroxyl group.",10.1021/acs.orglett.8b01851,2018-07-16,0.6637247006123638
Synthesis,An Efficient Synthesis of Nilotinib (AMN107),"A concise synthesis of AMN107, a compound currently undergoing several phase II/III clinical trials for chronic myelogenous leukemia is described. The new procedure reduces the number of synthetic steps from eight to four, with an overall yield of 65%.",10.1055/s-2007-983754,2007-07-03,0.6636270487951561
Synthesis,"A Short and Efficient Synthesis of (2S,3S,4S)-tert-Butyl 3,4-Dihydroxy-2-(methoxymethyl)-5-oxopyrrolidine-1-carboxylate",Asymmetric synthesis of the title compound was accomplished starting from L-serine. Stannoxane-mediated lactamization provided the key intermediate in good yield.,10.1055/s-0029-1218843,2010-06-25,0.663626925208629
Tetrahedron,Alkylhalides synthesis from selenoxides a new homologization process,,10.1016/s0040-4039(00)91759-3,1976-07-01,0.6636172196991013
Organic Process Research & Development,"Multigram Synthesis of BMS-929075, an Allosteric, Palm Site Inhibitor of HCV NS5B Replicase, Involving the Synthesis of a Highly Functionalized Benzofuran through a Telescoped Process","An efficient scale-up synthesis of 4-fluoro-2-(4-fluorophenyl)- N -methyl-5-(2-methyl-5-(1-(pyrimidin-2-yl)cyclopropylcarbamoyl)phenyl)benzofuran-3-carboxamide ( BMS-929075 ), an allosteric, palm site inhibitor of the HCV NS5B replicase, is described. The highlights of the process involve (a) the copper-mediated, one-pot synthesis of 2-(3-bromo-2-fluoro-6-methoxyphenyl)acetic acid ( 21 ) from regiospecifically lithiated 1-bromo-2-fluoro-4-methoxybenzene ( 13 ) and ethyl 2-bromoacetate ( 18 ); and (b) the formation of the highly functionalized benzofuran core 26 through a chromatography-free, telescoped process that proceeds via acylation and a subsequent concomitant demethylation and Boc deprotection using BBr 3, followed by an acid-catalyzed cyclization from Boc-protected 2-(3-bromo-2-fluoro-6-methoxyphenyl)- N -methylacetamide 23 . This process was applied to the preparation of 110 g of high-quality BMS-929075 to enable preclinical toxicology studies.",10.1021/acs.oprd.0c00198,2020-05-27,0.663581649272241
Organic Letters,Total Synthesis of Nesteretal A,"The enantioselective total synthesis of nesteretal A was achieved in 15 steps via biomimetic cascade hemiacetalizations at the final key step. Other key features of the total synthesis include Sharpless asymmetric dihydroxylation, diastereoselective 1,2-addition, Pd-catalyzed ene-type cyclization, and stereoselective epoxidation to construct a complex structure containing multiple quaternary carbons.",10.1021/acs.orglett.1c02478,2021-08-27,0.6635773968128008
Synthesis,"Expedient Access to A-Ring-γ-Dioxygenated Terpenoids: The First Synthesis of (13E)-ent-Labda-8(17),13-diene-3β,15,18-triol","A simple approach to A-ring-γ-dioxygenated terpenoids is described which involves two key steps, namely, selenium-catalyzed selective allylic chlorination of polyprenoids and titanocene-mediated radical cyclization of epoxypolyprenes. We have applied this synthetic route to the first synthesis of the diterpene, (13E)-ent-labda-8(17),13-diene-3β,15,18-triol. A stereoselective approach to this synthesis is also described.",10.1055/s-0029-1217094,2009-11-03,0.6635668131098883
Organic Letters,A Concise and Scalable Synthesis of High Enantiopurity (−)-<scp>d</scp>-<i>erythro</i>-Sphingosine Using Peptidyl Thiol Ester−Boronic Acid Cross-Coupling,"A short and efficient synthesis of high enantiopurity (-)-D-erythro-sphingosine has been achieved in 71% yield over 6 steps from N-Boc-L-serine. The key steps are high yield, racemization-free, palladium-catalyzed, copper(I)-mediated coupling of the thiophenyl ester of N-Boc-O-TBS L-serine with E-1-pentadecenyl boronic acid and the highly diastereoselective reduction of the resulting peptidyl ketone with LiAl(O-t-Bu)3H. By using this concise route (-)-D-erythro-sphingosine can be prepared on large scale and in high enantio- and diastereopurity (ee >99%, de up to 99%).",10.1021/ol070991m,2007-07-04,0.6635503971562087
Organic Letters,Asymmetric Total Synthesis of (+)-Intricenyne via an Endocyclization Route to Oxocane Skeleton,"The first total synthesis of (+)-intricenyne consisting of an oxocane skeleton was achieved via an extremely selective endocyclization strategy. The key features of the synthesis include a regio- and diastereoselective epoxide opening reaction, concise elaboration of oxocane cores via abnormally selective endocyclization ether ring formation, and versatile incorporation of the labile functional groups.",10.1021/acs.orglett.7b03370,2017-12-01,0.6635393741013126
Organic Letters,A Concise Asymmetric Route to <i>Nuphar</i> Alkaloids. A Formal Synthesis of (−)-Deoxynupharidine,"[reaction: see text] A stereocontrolled route to Nuphar alkaloids is described that employs a formal [3 + 3] cycloaddition strategy to assemble the piperidine nucleus. The addition of Pd-TMM complexes to aziridine 10 was found to be sluggish; however, the addition of a functionalized allyl Grignard reagent followed by a Mitsunobu condensation reaction provided 11 in high yield. The employment of this route in the formal synthesis of (-)-deoxynupharidine 1 is described.",10.1021/ol035156t,2003-08-28,0.6635348940629856
Journal of the American Chemical Society,Total Synthesis of (+)-Pleuromutilin,"An 18-step synthesis of the antibiotic (+)-pleuromutilin is disclosed. The key steps of the synthesis include a highly stereoselective SmI 2 -mediated cyclization to establish the eight-membered ring and a stereospecific transannular [1,5]-hydrogen atom transfer to set the C10 stereocenter. This strategy was also used to prepare (+)-12- epi -pleuromutilin. The chemistry described here will enable efforts to prepare new mutilin antibiotics.",10.1021/jacs.7b13260,2018-01-11,0.6635286691669788
Tetrahedron,β-Metallation of bridged alkenyl sulfones: Access to a key intermediate for epibatidine total synthesis,,10.1016/s0040-4039(97)10692-x,1998-02-01,0.6635147729968509
Synlett,Total Synthesis of Ascospiroketal B,"An enantioselective total synthesis of the marine tricyclic polyketide ascospiroketal B, previously isolated from the marine-derived fungus Ascochyta salicorniae, was accomplished in 21 steps by using an improved route. The intriguing 5,5-spiroketal-cis-fused-γ-lactone core was constructed through rearrangement of an epoxide, in conjunction with an acid-mediated spiroketalization.",10.1055/s-0040-1706405,2020-07-30,0.6634991089857526
Angewandte Chemie International Edition,An Enantiospecific Synthesis of the Potent Immunosuppressant FR901483,"An azaspiroannulation and an uncommon Mitsunobu reaction are the key steps in a convergent, enantioselective synthesis of the title compound 1. This potent immunosuppressant is derived from a fungus and is distinguished by an unusual monophosphate ester group and a novel architecture which comprises most of the atoms of two molecules of tyrosine.",10.1002/1521-3773(20001215)39:24<4593::aid-anie4593>3.0.co;2-x,2000-12-15,0.6634897678793034
Journal of Organic Chemistry,"Synthesis of (25<i>R</i>)-5α-Cholestane-3β,6β,15α,16β,26-pentol, a Cytostatic Starfish Steroid","The synthesis of (25 R )-5α-cholestane-3β,6β,15α,16β,26-pentol ( 1a ), a marine cytostatic steroid, has been achieved in 13 steps (7.8% overall yield) starting from commercially available diosgenin ( 2 ). A key step in the synthesis was the dimethyldioxirane oxidation of the enolsilane 16 to introduce the 15α-hydroxy group in the D ring.",10.1021/jo980266c,1998-06-01,0.6634803876400641
Synthesis,An Efficient Total Synthesis of (+)-Goniodiol,An efficient total synthesis of (+)-goniodiol was illustrated by using Carreira alkynylation and Sharpless asymmetric dihydroxylation as key steps.,10.1055/s-0030-1259431,2011-01-31,0.663471209550191
Tetrahedron,Ring isomerization of flavones. New synthesis of oroxylin-a and 7-methyl-oroxylin-A,,10.1016/s0040-4039(00)71086-0,1965-01-01,0.6634574521020562
Journal of Organic Chemistry,Total Synthesis and Structure Revision of Diplobifuranylone B,"An asymmetric total synthesis of diplobifuranylone B was achieved in 10 steps for the longest linear sequence and in 15.8% overall yield from commercially available methyl ( R )-(+)-lactate and l -glutamic acid. This synthesis features a stereoselective construction of the key 2,5-dihydrofuran ring in the natural product via a recently developed asymmetric gold catalysis. The stereochemical flexibility offered by the catalysis enables an expedient revision of the reported structure of diplobifuranylone B, where the relative stereochemistry of the 2,5-dihydrofuran moiety was previously misassigned as cis instead of trans.",10.1021/acs.joc.9b01613,2019-07-31,0.6634301027813286
Synlett,Total Synthesis of (±)-Moluccanic Acid Methyl Ester,"An effective total synthesis of the trinorditerpenoid moluccanic acid methyl ester has been achieved. The synthesis features a Robinson annulation, followed by aromatization to construct the aromatic ring and Baeyer–Villiger oxidation of the A ring to finish the target molecule.",10.1055/s-0031-1290956,2012-05-10,0.6634274336682999
Organic Letters,Three-Step Synthesis of Cyclopropyl Peptidomimetics,An efficient approach to novel cyclopropyl peptidomimetics has been developed. The synthetic route involves a cyclopropanation using ethyl (dimethylsulfuranylidene)acetate (EDSA) as the key step and affords a cyclopropyl peptidomimetic core in three steps from protected amino acid Weinreb amides.,10.1021/ol201828u,2011-08-24,0.6634211271069428
Organic Process Research & Development,Exploiting the Differential Reactivities of Halogen Atoms: Development of a Scalable Route to IKK2 Inhibitor AZD3264,An efficient and scalable synthesis of AZD3264 is described in which the differential reactivities of various halogen atoms have been employed. The process involves five linear chemical steps with three isolated stages starting from commercially available fragments.,10.1021/op500105n,2014-04-29,0.6634121078953299
Journal of Organic Chemistry,"Enantioselective Synthesis of Benzyl (1<i>S</i>,2<i>R</i>,4<i>R</i>)-4-(<i>tert</i>-Butoxycarbonylamino)-2-(hydroxymethyl)cyclohexylcarbamate Using an Iodolactamization As the Key Step","An efficient enantioselective synthesis of benzyl (1S,2R,4R)-4-(tert-butoxycarbonylamino)-2-(hydroxymethyl)cyclohexylcarbamate 2, an essential intermediate for a series of potent CCR2 antagonists, is described. The key step in the sequence is an iodolactamization to yield the highly functionalized (1R,2S,4S,5S)-tert-butyl 2-(benzyloxycarbonylamino)-4-iodo-7-oxo-6-azabicyclo[3.2.1]octane-6-carboxylate 11. An examination of the reaction mechanism within the 2-step iodolactamization sequence led to the discovery of a single-pot transformation of increased efficiency.",10.1021/jo9011249,2009-08-14,0.6634103835073267
Synlett,Efficient Synthesis of a New Potential Chelating Agent for Radioimmunotherapy,"The synthesis of a new rigid analogue of cyclohexyl-TTHA, an efficient lanthanide ligand, as well, as the first complexation trials are reported. This polyaminopolycarboxylic acid, Ph-DTHA 1, was obtained in five steps from phenylenediamine as starting product. The key intermediate was phenylenediethylenetetraamine 4, which after alkylation and hydrolysis gave the expected compound 1 with ten coordination centers.",10.1055/s-2002-35562,2002-01-01,0.6634078259665801
Journal of Organic Chemistry,Iromycins:  A New Family of Pyridone Metabolites from <i>Streptomyces</i> sp. II. Convergent Total Synthesis,"The total synthesis of iromycin A (1a), a microbial metabolite combining a novel structure with an interesting biological activity as a NO synthase inhibitor, was accomplished using a flexible and highly convergent approach. Thus, the ring fragment was prepared as 6-bromomethylpyrone 27 by acylation of the respective beta-ketoester 13 and subsequent lactonization of the thus-obtained beta,delta-diketoester 11, followed by bromination of the 6-methyl group. In addition, the unsaturated side chain was efficiently prepared as terminal alkyne 34 which was then carboaluminated to furnish the alkenyldimethylalane 35. The assembly of these two fragments was thoroughly studied using nickel, palladium, and copper catalysts yet only succeeded in the absence of any transition metal after formation of the respective lithium alkenyltrialkylalanate. Treatment of the coupled product 41 with liquid ammonia then completed the total synthesis which furnished an 18% overall yield over the nine steps of the longest linear sequence.",10.1021/jo070327j,2007-06-12,0.6633985272285369
Organic Letters,Synthetic Studies on Amphidinolide F: Exploration of Macrocycle Construction by Intramolecular Stille Coupling,"Exploration of an ambitious new strategy for the total synthesis of the cytotoxic marine natural product amphidinolide F is described, which features fabrication of the core structure from four readily accessible fragments and macrocycle construction through C9-C10 bond formation by intramolecular Stille coupling between an alkenyl iodide and alkenyl stannane. Efficient stereoselective synthesis of each of the four building-blocks and subsequent coupling of them to produce the requisite cyclization precursor has been accomplished, but suitable conditions for high-yielding palladium-mediated closure of the macrocycle to produce the fully protected amphidinolide F ring system have yet to be identified.",10.1021/acs.orglett.2c03045,2022-10-12,0.6633893746405263
Journal of Organic Chemistry,"A Synthetic Route to Tetrahydro-1<i>H</i>-azepino[4,3,2-<i>cd</i>]indoles via Ring-Opening Cyclization of Activated Azetidines with 4-Bromoindole: Toward a Vasopressin V2 Receptor Antagonist","A simple one-pot, two-step strategy for the synthesis of tetrahydro-1 H -azepino[4,3,2- cd ]indoles via Lewis acid-catalyzed S N 2-type ring opening of activated azetidines with 4-bromoindole, followed by a Pd-catalyzed intramolecular C–N cyclization reaction, with good to excellent yields is described. Utilizing this protocol, the vasopressin V2 receptor antagonist precursor has been synthesized easily. Enantioenriched tetrahydro-1 H -azepino[4,3,2- cd ]indoles were obtained by starting from enantiopure azetidine.",10.1021/acs.joc.4c01270,2024-08-05,0.6633492414075634
Tetrahedron,A new simple route to deoxyamino sugars from non-sugar material: synthesis of d-tolyposamine and 4-epi-d-tolyposamine and formal synthesis of d-vicenisamine,,10.1016/j.tetlet.2005.09.195,2005-10-21,0.6633420547100903
Journal of Organic Chemistry,Practical Asymmetric Synthesis of a Potent PDE4 Inhibitor via Stereoselective Enolate Alkylation of a Chiral Aryl−Heteroaryl Secondary Tosylate,"A practical, chromatography-free catalytic asymmetric synthesis of a potent and selective PDE4 inhibitor (L-869,298, 1) is described. Catalytic asymmetric hydrogenation of thiazole ketone 5a afforded the corresponding alcohol 3b in excellent enantioselectivity (up to 99.4% ee). Activation of alcohol 3b via formation of the corresponding p-toluenesulfonate followed by an unprecedented displacement with the lithium enolate of ethyl 3-pyridylacetate N-oxide 4a generated the required chiral trisubstituted methane. The displacement reaction proceeded with inversion of configuration and without loss of optical purity. Conversion of esters 2b to 1 was accomplished via a one-pot deprotection, saponification, and decarboxylation sequence in excellent overall yield.",10.1021/jo048156v,2005-03-16,0.6633336346873248
Organic Process Research & Development,"Route Development and Bulk Synthesis of CP-865,569","The synthesis of zwitterionic CP-865,569 by three different synthetic routes is described. The first two routes differ in the method of introducing the sulfonic acid at the penultimate step: by sulfite displacement of a benzylic chloride and by oxidation of a benzylic thioacetate. The third route is a convergent route to the drug candidate. The synthesis strategy was primarily driven by the need to introduce the sulfonic acid functionality at the final stage of the synthesis due to the high water solubility and low organic solubility of the desired product.",10.1021/op7000386,2007-06-15,0.6633137991331758
Organic Letters,A Concise Formal Synthesis of (−)-Hamigeran B,"A concise and efficient formal synthesis of (-)-hamigeran B is reported. The critical intermediate was synthesized from 3-methoxy-5-methylphenyl trifluoromethanesulfonate with an 11-steps 7.2% total yield route. The chiral quaternary carbon was efficiently and steroselectively constructed through an intermolecular Pauson-Khand reaction and a Claisen rearrangement reaction with >99% ee; the cyclohexane B was then closed through an aldehyde Friedel-Crafts cyclization. Lastly, the isopropenyl group of ring C was introduced through a Suzuki coupling reaction.",10.1021/ol400030a,2013-02-04,0.6633072612034109
Tetrahedron,Synthesis of the HIF-2α translation inhibitor compound 76 via a Japp-Klingemann coupling,,10.1016/j.tetlet.2019.03.005,2019-03-04,0.6632422692555543
Organic Process Research & Development,A Scalable Synthesis of an Atropisomeric Drug Substance via Buchwald–Hartwig Amination and Bruylants Reactions,"A practical, chromatography-free synthesis for a chemokine receptor antagonist NIBR-1282 ( 1 ) is described. Highlights of this scalable synthesis include (1) Buchwald–Hartwig amination reaction using ( t -Bu) 3 P as the ligand and 5–12 mol % of water as an additive affording 6 with yield increase of more than 2-fold; (2) a variant of the Bruylants reaction for the synthesis of α-methyl amine 10 via aminotriazole 15a, instead of classical amino nitrile 8; and (3) development of a crystallization-induced, atropisomer transformation leading to predominantly one atropisomer 1 . The new approach was employed for the manufacturing of kilogram quantities of the target active pharmaceutical ingredient.",10.1021/op400250s,2013-10-30,0.6632413016544327
Journal of the American Chemical Society,Enantioselective Synthesis of the Protein Phosphatase Inhibitor (−)-Motuporin,"A highly convergent asymmetric synthesis of the protein phosphatase inhibitor motuporin 1a is described. Synthesis and coupling of the individual peptide fragments [34 + 35 --> 51] followed by macrocyclization afforded the fully protected motuporin precursor 33, which is converted to the natural product by dehydration and ester hydrolysis. Six of the eight stereogenic centers associated with the natural product were introduced using asymmetric crotylsilane bond construction methodology. Our approach features an efficient Pd(0)-catalyzed cross-coupling reaction between a configurationally well-defined vinyl zinc intermediate 22 and an (E)-vinyl iodide 7, which afforded compound 43, resulting in the construction of the trisubstituted (E,E)-diene system of the motuporin side chain. Improved reaction conditions for macrocyclization in the formation of 33 are also detailed.",10.1021/ja0206700,2002-08-31,0.6632143300087295
Tetrahedron,"A new synthetic route to chiral, multiply functionalized cyclopentane rings",,10.1016/s0040-4039(00)79149-0,1992-09-01,0.6632062296045442
Synthesis,"A New Route for the Synthesis of Pyrido[2,3-<i>d</i>]pyridazines","All articles of this category A new simple route for the synthesis of pyrido[2,3- d ]pyridazines by reaction of acetyl and benzoyl cyanides with α,β-unsaturated nitriles is reported.",10.1055/s-1988-27617,1988-01-01,0.663203047057564
Organic Process Research & Development,"An Enantioselective Synthesis of (2<i>S</i>,3<i>R</i>)-3-(<i>N</i>-Benzyloxycarbonyl)amino-1-chloro-4-phenylthiobutan-2-ol, a Central Intermediate of Nelfinavir<sup>1</sup>","(2 S,3 R )-3-( N -Benzyloxycarbonyl)amino-1-chloro-4-phenylthiobutan-2-ol 1 is a central intermediate of nelfinavir 2, which, being a potent HIV protease inhibitor, represents one of the most clinically efficacious anti AIDS drugs. Thus, a practical enantioselective synthesis of 1 has been devised which employs sodium erythorbate 9 as a chiral starting material. Consisting of the total 14-step functional group manipulations that proceed via methyl (2 S,3 R )-4-hydroxy-2,3-epoxybutyrate 8, the synthetic processes can dispense with chromatographic purification and provide architecturally complex 1 in 17% overall yield under a strict control of stereochemistry.",10.1021/op010073i,2002-01-01,0.6632027603322809
Angewandte Chemie International Edition,Asymmetric Total Synthesis of a Pentacyclic <i>Lycopodium</i> Alkaloid: Huperzine‐Q,"Right on Q: the first asymmetric total synthesis of (-)-huperzine-Q, which possesses six stereogenic centers and a spiroaminal moiety, has been achieved in 19 steps and 16.4 % overall yield. This synthesis involved a novel stereoselective Pauson-Khand reaction, a vinyl Claisen rearrangement, and a biomimetic spiroaminal formation. TBDPS=tert-butyldiphenylsilyl.",10.1002/anie.201103550,2011-07-12,0.6631839470855165
Tetrahedron,Total synthesis of prostaglandins. V. A synthesis of (−)-prostaglandin E2 a totally asymmetric process.,,10.1016/s0040-4039(01)87625-5,1973-01-01,0.6631736835813045
Tetrahedron,"A highly enantioselective asymmetric hydrogenation route to β-(2R,3S)-methyltryptophan",,10.1016/s0040-4039(98)00604-2,1998-05-01,0.663114131034501
Organic Process Research & Development,"Practical Synthesis of 5-Fluoro-2-(piperidin-4-yloxy)pyrimidin-4-amine, a Key Intermediate in the Preparation of Potent Deoxycytidine Kinase Inhibitors","A practical synthesis of 5-fluoro-2-(piperidin-4-yloxy)pyrimidin-4-amine, a key intermediate in the preparation of a new class of potent deoxycytidine kinase (dCK) inhibitors, is described. The commercially available 2,4-dichloro-5-fluoropyrimidine ( 12 ) is converted in four telescoped steps to tert -butyl 4-(4-amino-5-fluoropyrimidin-2-yloxy)piperidine-1-carboxylate ( 6a ) which upon deprotection gives 5-fluoro-2-(piperidin-4-yloxy)pyrimidin-4-amine dihydrochloride ( 1a ) in about 68% overall yield. This process proved to be an economical alternative to a Mitsunobu-based synthesis.",10.1021/op900060u,2009-04-30,0.6630844083645637
Tetrahedron,Novel synthetic approach to alfaprostol key intermediates via Stille coupling with an alkyne,,10.1016/j.tetlet.2017.04.091,2017-04-27,0.6630498679158578
Organic Process Research & Development,Development of an Efficient Process Towards the Benzimidazole BYK308944: A Key Intermediate in the Synthesis of a Potassium-Competitive Acid Blocker,"An entirely new synthesis of the important benzimidazole building block BYK308944 was elaborated using the Stobbe reaction as central element. BYK308944 constitutes an important intermediate for the preparation of 3,6,7,8-tetrahydrochromeno[7,8- d ]imidazoles as potassium-competitive acid blockers. The new route relies on the hydroxymethylation of 1,2-dimethylimidazole as cheap starting material followed by oxidation of the corresponding alcohol and Stobbe condensation of the resulting aldehyde with diethyl succinate. All synthetic steps of this new approach were optimized particularly with the goal to establish a process amenable for large-scale preparation.",10.1021/op9002505,2009-12-08,0.6630414764422006
Journal of the American Chemical Society,Synthesis of Pleuromutilin,"Synthesis of a potent inhibitor of bacterial protein synthesis, pleuromutilin, is described. Assembly of the critical cyclooctane fragment relies on an oxidative ring-expansion, and complete stereochemical relay in the synthetic sequence is enabled by the judicious choice of tactics. The requisite connectivity pattern of the perhydroindanone motif is rapidly established in a sequence of cycloaddition and radical cyclization events. Application of this strategy allows for preparation of the target natural product in 16 steps from commercially available material.",10.1021/jacs.2c04708,2022-06-02,0.6630407343899976
Journal of Organic Chemistry,Total Synthesis of (−)-Balanol,"The efficient total synthesis of (−)-balanol, a potent inhibitor of the protein kinase C, is described. (−)-Balanol consists of a chiral hexahydroazepine-containing fragment and a benzophenone fragment, both of which were prepared via novel synthetic routes. The hexahydroazepine fragment was prepared in racemic form through either Bu 3 SnH- or SmI 2 -promoted radical cyclization of oxime ethers 2ab intramolecularly connected with the formyl group. SmI 2 -promoted radical cyclization of 2b was found to be particularly successful in the selective synthesis of the seven-membered trans -amino alcohol 8b . Preparation of the enantiomerically pure hexahydroazepine-containing fragment was achieved through the enantioselective enzymatic acetylation of racemic alcohol 9, employing the immobilized lipase from Pseudomonas sp. The benzophenone fragment was prepared in short steps through a biomimetic oxidative anthraquinone ring cleavage starting from commercially available natural chrysophanic acid 15c . This reaction proceeded via [4 + 2]-cycloaddition of singlet oxygen to anthracene derivative 17c, followed by Baeyer−Villiger-type rearrangement of the resulting hydroperoxide to afford the benzophenone derivatives 22 and 23 .",10.1021/jo980208r,1998-06-01,0.6630209030971027
Synthesis,"A Novel Route to 1,4-Diketones and its Application to<i>cis</i>-Jasmone and Dihydrojasmone Synthesis",,10.1055/s-1978-24715,1978-01-01,0.663008779107781
Organic Process Research & Development,Scalable Synthesis of a Nonracemic α-Arylpropionic Acid via Ketene Desymmetrization for a Glucokinase Activator,"Process research and development for a synthesis of the chiral carboxylic acid ( R )-2 as a key intermediate of the glucokinase activator ( R )-1 is described. The construction of the stereocenter at the α-carbon is a key point for the synthesis of ( R )-2 . The proposed process utilizes desymmetrization of a ketene in situ generated from the corresponding racemic carboxylic acid Rac -2 with ( R )-pantolactone as a chiral auxiliary followed by hydrolysis of the resulting ester. This key step has been successfully scaled up to 20 kg, which demonstrates that this synthetic approach is comparable with a previously reported approach via enantioselective hydrogenation.",10.1021/op400354g,2014-02-13,0.6629880664530065
Organic Letters,Enantioselective Total Synthesis of (+)-Rogioloxepane A,"[reactiojn: see text] The enantioselective synthesis of (+)-rogioloxepane A has been achieved in 21 steps from 1,5-hexadien-3-ol. The key steps in the synthesis are an asymmetric glycolate alkylation leading to the diene 2 and a subsequent ring-closing metathesis to construct the oxepene core.",10.1021/ol034923l,2003-07-22,0.6629706405279994
Organic Process Research & Development,"A Practical Synthesis of the Platelet Fibrinogen Antagonist, Elarofiban","Elarofiban is a novel, nonpeptide, orally active fibrinogen receptor antagonist useful for the treatment of platelet mediated thrombotic disorders (Costanzo, M. J.; Hoekstra, W. J.; Maryanoff, B. E. WO, 97/41102, 1997). Herein we describe the process research that was carried out for the synthesis of elarofiban that eventually led to the development of a safe and cost-effective commercial scale process.",10.1021/op034103o,2003-10-01,0.662965016904249
Journal of the American Chemical Society,Migratory Hydroamination:  A Facile Enantioselective Synthesis of Benzomorphans,"We describe a highly efficient, general strategy for the enantioselective synthesis of benzomorphans (45-46% overall yield from commercially available material). The new synthesis demonstrates the effectiveness of an unprecedented diastereoselective cycloisomerization via migratory hydroamination and the power of palladium-catalyzed asymmetric allylic alkylation (AAA) of simple ketone enolates in the context of complex synthesis. The strategy outlined here for the enantioselective synthesis of three contiguous stereogenic centers and the novel cycloisomerization should have many applications in alkaloid synthesis.",10.1021/ja0360539,2003-06-28,0.662953657503569
Synlett,Asymmetric Synthesis of (-)-Tetrahydrolipstatinfrom a β-Hydroxy-δ-oxo Sulfoxide,"An asymmetric synthesis of (-)-tetrahydrolipstatin is ­described. A palladium-catalyzed regioselective oxidation of an alkene to a ketone, highly diastereoselective reduction of a β-­hydroxy ketone, selective oxidation of a diol, and modular synthesis are the key features of the synthesis.",10.1055/s-0029-1216722,2009-04-17,0.6629400884232742
Organic Process Research & Development,The Efficient Synthesis of Disodium Disuccinate Astaxanthin (Cardax),"A practical procedure is described for the multigram preparation of disodium disuccinate derivatives of synthetic astaxanthin (Cardax) [from all- trans -(all- E )-3 S,3‘ S-, meso -(3 R,3‘ S )-, and 3 R,3‘ R -dihydroxy-β,β-carotene-4,4‘-dione) in a 1:2:1 statistical mixture of stereoisomers, as well as from the individual component stereoisomers]. Process development eliminated chromatographic separations, controlled geometric isomerization, and improved the overall yield of the two-step process, with significant improvements in both the yield and purity of Cardax. Bulk chromatographic separation of the diastereomeric dicamphanic acid ester of synthetic astaxanthin was performed by modifications of the published procedure to subsequently generate multigram quantities of each stereoisomer of disodium disuccinate of astaxanthin.",10.1021/op049909i,2004-08-12,0.6629157783563321
Angewandte Chemie International Edition,Enantioselective Hydrogenation of Allylphthalimides: An Efficient Method for the Synthesis of β‐Methyl Chiral Amines,High yields and up to 98 % ee have been achieved by asymmetric hydrogenation of allylphthalimides followed by hydrolysis to give β-methyl chiral amines by using a Ru–C3-tunephos catalyst (see scheme). The synthetic utility of this procedure has been demonstrated through the synthesis of the key intermediate of the LTs receptor antagonist (Zeneca ZD 3532).,10.1002/anie.200501332,2005-06-27,0.6629144510948126
Synlett,Synthesis of Dictyopterene A,The total synthesis of dictyopterene A was accomplished via an enantiomerically pure cyclopropylboronic ester building block. Crucial olefination steps were carried out employing the Julia-Kocienski as well as the Wittig reactions. The Matteson homologation was the final key step for the total synthesis.,10.1055/s-2008-1042918,2008-03-17,0.6629034808630292
Tetrahedron,"A new route for the efficient synthesis of (±)ochromycinone, a naturally occurring benz[a] anthraquinone.",,10.1016/s0040-4039(00)96297-x,1987-01-01,0.6628529853654909
Journal of Organic Chemistry,Total Synthesis of Microtubule-Stabilizing Agent Ceratamine A,"The total synthesis of ceratamine A, a natural microtubule-stabilizing agent with unusual cellular effects, has been accomplished starting from 5-methoxybenzimidazole in 10 steps in an overall yield of 12.7%. The key steps in the synthesis involved the Schmidt rearrangement to construct the azepine ring, the alkylation of lactam to introduce the C-5 benzylic side chain, and the highly economical SNAr reaction to install the C-2 methylamine residue.",10.1021/jo402165n,2013-12-04,0.6628263257585898
Journal of the American Chemical Society,Total Synthesis and Structure Revision of the Marine Metabolite Palmerolide A,"We describe a highly convergent and flexible synthesis of the novel antarctic marine metabolite palmerolide A an effort leading to a reformulation of palmerolide A as ent- 24, the enantiomer of the C19,C20-bis-epimer of the original proposed structure 1 . Our total synthesis features a highly stereoselective vinylogous Mukaiyama aldol reaction to introduce the C19,C20-stereodiad, an efficient Suzuki cross-coupling to install the endocyclic diene unit, and an intramolecular Horner−Wadsworth−Emmons olefination to close the macrocycle. Starting from fragments 2, 3 ( ent - 3 ), and 13 (prepared in five to eight steps each, 38−70% overall yield) the synthesis of the proposed structure 1 and the enantiomer of palmerolide A ( 24 ) was completed in an additional 14 steps (22 steps longest linear sequence).",10.1021/ja0715142,2007-04-26,0.6627872362191665
Organic Process Research & Development,"Novel Stereoselective Syntheses of the Fused Benzazepine Dopamine D<sub>1</sub> Antagonist (6a<i>S</i>,13<i>b</i><i>R</i>)-11-Chloro-6,6a,7,8,9,13b-hexahydro-7-methyl- 5<i>H</i>-benzo[<i>d</i>]naphth[2,1-<i>b</i>]azepin-12-ol (Sch 39166):  2. <scp>l</scp>-Homophenylalanine-Based Syntheses","Two enantioselective syntheses of the fused benzazepine dopamine D 1 antagonist (6a S,13b R )-11-chloro-6,6a,7,8,9,13b-hexahydro-7-methyl-5 H -benzo[ d ]naphth[2,1- b ]azepin-12-ol ( 1 ) are described in which the starting material is (+)- l -homophenylalanine ( 6 ). In the first approach, methyl (2 S )-(1,2,3,4-tetrahydro-1-oxo-2-naphthalenyl)carbamate ( 5 ) is prepared by intramolecular Friedel−Crafts cyclization of N -carbomethoxy (+)- l -homophenylalanine ( 9 ). Subsequent alkylation of 5 with (4-chloro-3-methoxyphenyl)magnesium bromide, deoxygenation with Et 3 SiH, reduction, alkylation, and epimerization yields (+)- trans -(1 R,2 S )-1-(4-chloro-3-methoxyphenyl)- N -(2,2-dimethoxyethyl)-1,2,3,4-tetrahydro- N -methyl-2-naphthalenamine ( 2 ), a key intermediate in the previously described route to 1 (Draper, R. W.; Hou, D.; Iyer, R.; Lee, G. M.; Liang, J. T.; Mas, J. L.; Tormos, W.; Vater, E. J.; Günter, F.; Mergelsberg, I.; Scherer, D. Org. Process Res. Dev. 1998, 2, XXXXX). A complementary route to 2 is also described in which arylation of an N-protected, carboxyl-activated (+)- l -homophenylalanine affords (2 S )-1-(4-chloro-3-methoxyphenyl)-2-(methoxycarbamoyl)-4-phenyl-1-butanone ( 26 ). Reduction of the latter compound followed by an acid-catalyzed, diastereoselective cyclization affords (+)-(1 R,2 S )-[1-(4-chloro-3-methoxyphenyl)-1,2,3,4-tetrahydro-2-naphthalenyl]carbamate ( 16 ), which is reduced and alkylated as before to produce 2 .",10.1021/op970122k,1998-04-28,0.6627751657864672
Journal of the American Chemical Society,Total Synthesis of (+)-Yatakemycin,"A convergent total synthesis of (+)-yatakemycin was accomplished in a 20-step sequence in an overall yield of 13%. The synthesis features the regioselective ring opening of (S)-epichlorohydrin with 2,6-dibromophenyllithium species, the mild copper-mediated aryl amination utilizing the combination of CuI and CsOAc, and the efficient deprotection of benzyl groups of aryl benzyl ether with BCl3 in the presence of pentamethylbenzene.",10.1021/ja0619455,2006-05-12,0.6627148883729921
Organic Letters,Stereodivergent Synthesis of Pseudotabersonine Alkaloids,An eight-step stereodivergent synthesis of enantiomerically pure (-)-14-epi-pseudotabersonine and (+)-pseudotabersonine has been developed from a common N-tert-butanesulfinyl ketimine key intermediate.,10.1021/acs.orglett.7b02635,2017-09-13,0.6627122305927161
Journal of Organic Chemistry,The Enantioselective Synthesis of (−)-Lycoramine with the Birch−Cope Sequence,"The first enantioselective synthesis of (-)-lycoramine has been achieved in 14 steps and 5% overall yield from the biaryl derivative 1. The synthesis applies the previously developed Birch-Cope sequence to create the key arylic quaternary stereocenter of (-)-lycoramine with excellent enantioselective control. The product of the Birch-Cope sequence, a versatile 4,4-disubstituted-2-carboxamide-2-cyclohexen-1-one, was elaborated through an intramolecular conjugate addition of a phenol to create the dihydrofuran ring. Chemoselective elaboration of the allyl group into an amide followed by a modified Pictet-Spengler reaction generated the azepine ring.",10.1021/jo070976v,2007-08-04,0.6627104365396678
Journal of the American Chemical Society,Total Synthesis of (−)-Rauvomine B via a Strain-Promoted Intramolecular Cyclopropanation,"We describe the first total synthesis of the unusual cyclopropane-containing indole alkaloid (−)-rauvomine B via a strategy centered upon intramolecular cyclopropanation of a tetracyclic N -sulfonyltriazole. Preparation of this precursor evolved through two generations of synthesis, with the ultimately successful route involving a palladium-catalyzed stereospecific allylic amination, a cis -selective Pictet–Spengler reaction, and ring-closing metathesis as important bond-forming reactions. The key cyclopropanation step was found to be highly dependent on the structure and conformational strain of the indoloquinolizidine N -sulfonyltriazole precursor, the origins of which are explored computationally through DFT studies. Overall, our synthesis proceeds in 11 total steps and 2.4% yield from commercial materials.",10.1021/jacs.4c07669,2024-07-23,0.662680415445317
Organic Letters,Synthesis of Mycobacterial Triacylated Phosphatidylinositol Dimannoside Containing an Acyl Lipid Chain at 3-O of Inositol,"A seven-step synthesis of triacylated phosphatidylinositol dimannoside is described from myo-inositol 1,3,5-orthoformate. It proceeded in 31% overall yield via a highly regioselective and stereoselective 2,6-di-O-D-mannosylation as the key step.",10.1021/ol1008137,2010-05-05,0.6626793006141714
Journal of Organic Chemistry,Total Syntheses of Cladoacetals A and B: Confirmation of Absolute Configurations,"The first enantioselective syntheses of cladoacetals A (1a, overall yield: 16%) and B (1b, overall yield: 34%) from crotonaldehyde in nine and seven steps, respectively, have been accomplished. Sharpless asymmetric dihydroxylation, Suzuki coupling, and acid-catalyzed intramolecular acetalization were the key steps in the syntheses. The absolute configuration of natural (+)-cladoacetal A was affirmed to be 1S,3S,4R, whereas that of (-)-cladoacetal B was affirmed to be 1R,3S,4S.",10.1021/jo300923e,2012-06-27,0.6626070860899934
Journal of the American Chemical Society,Total Synthesis of (−)-Tuberostemonine,"The first total synthesis of the complex pentacyclic Stemona alkaloid tuberostemonine was accomplished in 24 steps and in 1.4% overall yield from a hydroindole intermediate which is readily obtained in three steps from Cbz-l-tyrosine. An innovative synthetic strategy was applied that relays the single stereocenter of the amino acid precursor into nine of the ten stereogenic carbons of the target molecule. Among the highlights of the synthetic methodology are the 3-fold use of ruthenium catalysis, first in an azepine ring-closing metathesis and then in an alkene isomerization followed by a cross-metathesis propenyl-vinyl exchange, as well as the stereoselective attachment of the gamma-butyrolactone moiety to the core tetracycle by use of a lithiated ortho ester.",10.1021/ja028603t,2002-11-21,0.6625464946855709
Journal of the American Chemical Society,Synthesis and Complete Stereochemical Assignment of Psymberin/Irciniastatin A,"We describe a concise and flexible synthetic avenue for the preparation of compounds with structures relevant to those proposed for the novel marine-derived differential cytotoxins psymberin and irciniastatin A. Our efforts led to their complete stereochemical assignment and the notion that psymberin and irciniastatin A are identical compounds. Our total synthesis features an interesting termini-differentiating lactolization of a dialdehyde obtained from a C2-symmetrical bis-olefin precursor, a mild platinum-catalyzed hydrolysis of an epimerizable nitrile, a novel protocol to prepare sensitive methyl imidates, and a one-pot conversion of these imidates to N-acyl aminals. Starting from fragments 5-7 (prepared in 7-8 steps each, 30-49% overall yield) the synthesis of psymberin/irciniastatin A was completed in an additional 9 steps and 30% yield (17 steps longest linear sequence, 8.9% overall).",10.1021/ja0537068,2005-07-21,0.6625380942070339
Organic Process Research & Development,"Practical Synthetic Method of (2<i>Z</i>,3<i>E</i>)-1,4-Diphenylbutadiene T-2639, an Inhibitor of Plasminogen Activator Inhibitor-1 (PAI-1) Production","A practical synthetic method of (2 Z,3 E )-1,4-diphenylbutadiene derivative T-2369 ( 1 ), a potent inhibitor of plasminogen activator inhibitor-1 (PAI-1) production, is described. Conditions of Stobbe condensation in the conventional synthesis of T-2369 were examined, and a new method to efficiently synthesize the key intermediate, (2 Z,3 E )- 2,was derived. (2 Z,3 E )- 2 was selectively obtained in 82% (with 91:9 selectivity) by predominant precipitation of (2 Z,3 E )- 2 Na salt and in situ isomerization of (2 E,3 E )- 2 to (2 Z,3 E )- 2 .",10.1021/op9000719,2009-05-28,0.6624886839975461
Journal of Organic Chemistry,Total Synthesis of Camptothecin and SN-38,"A new practical and concise total synthesis of enantiopure camptothecin and SN-38 (14% overall yield, 99.9% ee and 99.9% purity) was described, starting from inexpensive and readily available materials. The development of column chromatography-free purification was achieved in all steps, which offers an economic industrial process to the camptothecin-family alkaloids.",10.1021/jo201974f,2011-12-13,0.6624465913334946
Organic Process Research & Development,Preparation of the HIV Attachment Inhibitor BMS-663068. Part 4. Synthesis of the 6-Azaindole Core,"We report research focused on the construction of the 6-azaindole core, a key intermediate in the synthesis of the clinical candidate BMS-663068. The work describes an efficient and scalable method to access the 6-azaindole from a protected 3-ketopyrrole via a Pictet–Spengler cyclization and a radical-mediated aromatization. The process reported herein has been successfully implemented on the multikilogram scale to support preclinical development and clinical studies of BMS-663068.",10.1021/acs.oprd.7b00152,2017-08-09,0.6624343361233767
Tetrahedron,Novel synthetic route γ-oxo-acrylates application to the synthesis of pyrenophorin antibiotic,,10.1016/s0040-4039(01)81316-2,1984-01-01,0.6624179040879717
Journal of Organic Chemistry,Divergent Approach to the Bisanthraquinone Natural Products: Total Synthesis of (<i>S</i>)-Bisoranjidiol and Derivatives from Binaphtho-<i>para</i>-quinones,"The development of the first asymmetric synthesis of a chiral anthraquinone dimer is outlined, resulting in the first total synthesis of (S)-bisoranjidiol. Rather than a biomimetic dimerization retrosynthetic disconnection, the anthracenyl ring systems are generated after formation of the axially chiral binaphthalene framework. This synthetic strategy has enabled the synthesis of several analogues. Key features of the synthesis include the enantioselective coupling of a hindered 2-naphthol containing substitution peri to the site of C-C bond formation, the regioselective oxidation of 8,8'-hydroxylated binaphthols to binaphtho-para-quinones, and a tandem regioselective Diels-Alder/aromatization reaction.",10.1021/jo302364h,2012-12-18,0.6624177567458158
Journal of Organic Chemistry,A Chiron Approach to Aminocytitols by Petasis-Borono-Mannich Reaction: Formal Synthesis of (+)-Conduramine E and (−)-Conduramine E,A chiron approach to a stereoselective route for the synthesis of aminocytitols from carbohydrates is described. The formal synthesis of (+)-conduramine E and (-)-conduramine E was achieved by utilizing this strategy. The key features of the synthetic strategy include one-pot three-component Petasis-Borono-Mannich reaction to introduce the syn-β-amino alcohol functionality of conduramine E and ring-closing metathesis to construct its carbocyclic core. The present synthetic approach paves the way for stereoselective synthesis of several conduramines starting from carbohydrates.,10.1021/jo300804d,2012-08-17,0.6624070439585296
Tetrahedron,"Asymmetric synthesis of the diastereoisomers of the leukotriene B4 antagonist, U-75302",,10.1016/s0040-4039(01)93452-5,1989-01-01,0.6624021427357164
Organic Process Research & Development,Mitsunobu Inversion of a Secondary Alcohol with Diphenylphosphoryl azide. Application to the Enantioselective Multikilogram Synthesis of a HCV Polymerase Inhibitor,"The development of a practical synthesis of the hepatitis C virus polymerase inhibitor 1 was necessary to support preclinical safety and human clinical studies. Significant challenges face the process chemist in developing a route to 1 that is amenable to multikilogram operation. In particular, an efficient construction of the eight-membered dihydroindolobenzoxazocine ring and enantioselective synthesis of the secondary amine stereocenter are required. This article describes our process development of a Mitsunobu protocol to achieve the latter goal which uses diphenylphosphoryl azide at ambient temperature to invert a scalemic secondary alcohol. The hazard evaluation performed to establish the safety of this protocol and allow pilot-plant introduction at >8.0 kg scale is discussed. Overall, an enantioselective synthesis of 1 by way of seven isolated intermediates in 32% overall yield was developed from commercially available materials. This allowed us to prepare over 3 kg of the targeted drug candidate.",10.1021/op200002u,2011-03-02,0.6623787071550246
Journal of Organic Chemistry,A Simple and Efficient Synthetic Route to Chiral Isopavines. Synthesis of (−)-<i>O</i>-Methylthalisopavine and (−)-Amurensinine,"The isopavinan alkaloids (−)- O -methylthalisopavine ( 7a ) and (−)-amurensinine ( 7d ) have been synthesized in good yield and high ee from the appropriate 1,2-diarylethylamine derivatives using optically active β-amino alcohols as chiral support. This synthetic route employs as key steps the alkylation reaction of the azomethine derivatives 2 with Grignard reagents 1 and a novel one-pot double-intramolecular cyclization of the adequately functionalized 1,2-diarylethylamines 5 to afford a series of optically active isopavines 6a−d and 7a−d .",10.1021/jo9708102,1997-10-01,0.6623363694329587
Angewandte Chemie International Edition,<i>trans</i>‐Hydrogenation: Application to a Concise and Scalable Synthesis of Brefeldin A,"The important biochemical probe molecule brefeldin A (1) has served as an inspirational target in the past, but none of the many routes has actually delivered more than just a few milligrams of product, where documented. The approach described herein is clearly more efficient; it hinges upon the first implementation of ruthenium-catalyzed trans-hydrogenation in natural products total synthesis. Because this unorthodox reaction is selective for the triple bond and does not touch the transannular alkene or the lactone site of the cycloalkyne, it outperforms the classical Birch-type reduction that could not be applied at such a late stage. Other key steps en route to 1 comprise an iron-catalyzed reductive formation of a non-terminal alkyne, an asymmetric propiolate carbonyl addition mediated by a bulky amino alcohol, and a macrocyclization by ring-closing alkyne metathesis catalyzed by a molybdenum alkylidyne.",10.1002/anie.201411618,2015-02-04,0.6623072776660786
Synlett,A Concise Synthetic Approach to (+)-Valienamine Starting from Garner's Aldehyde,"A synthesis of (+)-valienamine was achieved starting from Garner’s aldehyde in ten steps and 23% overall yield. A unique feature of the synthetic route is that an acyclic precursor was constructed, using diastereoselective antireductive coupling reaction of alkyne and Garner’s aldehyde as the key step, which was then cyclized in an intramolecular aldol reaction to form the valienamine skeleton.",10.1055/s-0031-1290614,2012-03-15,0.6623070792950103
Organic Letters,"Efficient Syntheses of the Unknown Quinolino[2,3-<i>c</i>]cinnolines; Synthesis of Neocryptolepines","A facile, efficient, three-step protocol for the synthesis of the unknown quinolino[2,3-c]cinnoline 5 is introduced. In addition, a new approach for the preparation of the biologically active neocryptolepines 8 in good overall yields is described.",10.1021/ol102376a,2010-11-10,0.6622528895035367
Organic Process Research & Development,A New Synthetic Route to Avibactam: Lipase Catalytic Resolution and the Simultaneous Debenzylation/Sulfation,"High Resolution Image Download MS PowerPoint Slide An efficient synthesis of avibactam starting from commercially available ethyl-5-hydroxypicolinate was completed in 10 steps and 23.9% overall yield. The synthesis features a novel lipase-catalyzed resolution, in the preparation of (2 S,5 S )-5-hydroxypiperidine-2-carboxylate acid, which is a valuable precusor of the key intermediate ethyl (2 S,5 R )-5-((benzyloxy)amino)piperidine-2-carboxylate. An optimized one-pot debenzylation/sulfation reaction, followed by cation exchange, gave the avibactam sodium salt on a 400.0 g scale.",10.1021/acs.oprd.7b00290,2017-12-07,0.6622515178271328
Organic Letters,First Total Synthesis of (±)-Taxifolial A and (±)-<i>iso</i>-Caulerpenyne,The first synthesis of (+/-)-taxifolial A and iso-caulerpenyne was accomplished. The key steps in the sequence are (1) the stereoselective assembly of a vinyltin derived from butynediol and a functionalized aldehyde and (2) the construction of the dienyne moiety via a Stille cross-coupling.,10.1021/ol015903r,2001-05-01,0.6622477142177082
Journal of the American Chemical Society,Total Synthesis of (−)-Maximiscin,"A short, enantioselective synthesis of (-)-maximiscin, a structurally intriguing metabolite of mixed biosynthetic origin, is reported. A retrosynthetic analysis predicated on maximizing ideality and efficiency led to several unusual disconnections and tactics. Formation of the central highly oxidized pyridone ring through a convergent coupling at the end of the synthesis simplified the route considerably. The requisite building blocks could be prepared from feedstock materials (derived from shikimate and mesitylene). Strategies rooted in hidden symmetry recognition, C-H functionalization, and radical retrosynthesis played key roles in developing this concise route.",10.1021/jacs.0c03202,2020-04-25,0.6622374790246136
Tetrahedron,Improved synthetic route for the GluN2-specific NMDA receptor glycine site agonist AICP,,10.1016/j.tetlet.2020.151653,2020-01-21,0.6622346632737836
Tetrahedron,Towards the synthesis of swinholide A and scytophycin C. A highly stereocontrolled synthesis of (−)-pre-swinholide A,,10.1016/s0040-4039(00)76920-6,1994-05-01,0.662224924442584
Tetrahedron,Total synthesis of modified jstx toxins: reductive alkylation is a practical route to hexahydropyrimidine polyamine amides,,10.1016/0040-4039(95)01995-t,1995-12-01,0.6622247489758355
Journal of the American Chemical Society,Total Synthesis of (+)-Cylindramide A,A total synthesis of cylindramide A has been completed in 19 steps. The key step of the synthesis is a tandem ring-opening-ring-closing-cross metathesis that converts a readily available norbornene into an advanced intermediate.,10.1021/ja057899a,2006-01-10,0.6622227226227215
Organic Letters,"Catalytic Asymmetric Synthesis of Piperidines from Pyrrolidine: Concise Synthesis of L-733,060","Catalytic asymmetric deprotonation-aldehyde trapping-ring expansion from a 5- to a 6-ring delivers a concise route to each stereoisomer of beta-hydroxy piperidines starting from N-Boc pyrrolidine. The methodology is utilized in a 5-step catalytic asymmetric synthesis of the neorokinin-1 receptor antagonist, (+)-L-733,060.",10.1021/ol900366m,2009-04-01,0.6621972693763146
Journal of Organic Chemistry,"A Chiral Synthesis of (−)-Spiro[1-azabicyclo[2.2.2]octane-3,5‘- oxazolidin-2‘-one]:  A Conformationally Restricted Analogue of Acetylcholine That Is a Potent and Selective α7 Nicotinic Receptor Agonist","A direct, short chiral synthesis of the selective alpha7 nicotinic receptor agonist (-)-spiro[1-azabicyclo[2.2.2]octane-3,5'-oxazolidin-2'-one] (AR-R17779) is presented. The key step utilized attack of the dianion of the (R)-HYTRA ester [(R)-(+)-2-hydroxy-1,2,2-triphenylethyl acetate] on quinuclidin-3-one, followed by a selective precipitation of the diasteriomeric tertiary alcohol that led to (S)-(-)-AR-R17779 in two additional steps.",10.1021/jo049404q,2004-08-26,0.6621892499974883
Organic Process Research & Development,An Improved Process for the Large-Scale Preparation of Antirheumatic Agent MX-68,"A large-scale preparation route of MX-68, a novel MTX derivative bearing a dihydro-2 H -1,4-benzothiazine moiety and l -homogulutamic acid, is described. The original route that is a laboratory-scale synthesis for preclinical study has been improved. The improved process involves the following features: each step does not use haloalkane solvents, corrosive reagents, and chromatographic purification, and the formation of the major impurity at the final step is minimized. This improvement has enabled us to supply sufficient quantities of MX-68, which is required for both the toxicity test and the clinical study.",10.1021/op049867y,2004-09-21,0.66216296778242
Organic Letters,"Total Synthesis of (±)-Galanthamine via a C3-Selective Stille Coupling and IMDA Cycloaddition Cascade of 3,5-Dibromo-2-pyrone","A new efficient synthetic route to (+/-)-galanthamine was devised by using a tandem C3-selective Stille coupling-IMDA cascade of 3,5-dibromo-2-pyrone as a key strategy.",10.1021/ol100617u,2010-04-08,0.6621609448170088
Organic Process Research & Development,"Development of a Scalable, Stereoselective Second-Generation Route for CXCR7 Antagonist ACT-1004-1239 via Chiral Enamine Reduction and a Novel Telescoped Sequence of Transesterification, <i>cis</i>-to-<i>trans</i> Epimerization, and Saponification","The rapid development of a stereoselective route for CXCR7 antagonist ACT-1004-1239 was needed, as the large-scale chromatographic separation of enantiomers was not a viable option for a resupply campaign that targeted >30 kg of API. The key to success was the stereoselective reduction of a chiral enamine derived from inexpensive ( S )-α-methylbenzylamine. The reduction showed good selectivity for the desired cis -3 R,4 S -isomer, and the pure diastereomer (d.r. >98:2) was isolated as its TFA salt. After removal of the ethylbenzyl group and amide coupling with 5-(2,4-difluorophenyl)isoxazole-3-carboxylic acid, the enantiopure cis -3 R,4 S -amide was isolated. The subsequent epimerization of the 3-position adjacent to the methyl ester turned out to be a formidable challenge, as the standard conditions with NaOMe led to the formation of a thermodynamic mixture of the cis and trans isomers (final ratio of ∼1:4). Therefore, a new procedure was developed in which the methyl ester was transesterified in situ to the isopropyl ester with KOiPr in iPrOH, followed by epimerization to the trans -iPr-ester (final cis: trans ratio 5:95). After saponification with aqueous KOH, the desired trans -3 S,4 S -acid was isolated in overall 76% yield. After amide coupling and Boc deprotection, the final reductive amination with cyclopropanecarboxaldehyde was also vastly improved. A novel NaBH(OAc) 3 solution in DMSO was used for the reaction and cleanly provided the API with high purity after simple aqueous quench without the need for any solvent switches or aqueous workups. As a proof of concept, 240 g of API was produced in house with the novel stereoselective route, which was then also used to produce over 30 kg of GMP material at an external manufacturer for Phase 2 clinical studies.",10.1021/acs.oprd.3c00446,2024-01-22,0.6621595702103596
Angewandte Chemie International Edition,Total Synthesis of (−)‐Allosecurinine,"Safe and secure: An efficient methodology which provides access to homochiral 2,5-cis pyrrolidines in excellent yields starting from chiral alkoxyamine cyclopropanes was used in the total synthesis of (−)-allosecurinine (see scheme). The synthesis proceeds with enantiomeric purity in 15 steps with an overall yield of 5 %. OTf: trifluoromethanesulfonate, Boc: tert-butoxycarbonyl, PG: protecting group.",10.1002/anie.200803257,2008-09-03,0.6621254855955568
Angewandte Chemie International Edition,Enantioselective Palladium‐Catalyzed Dearomative Cyclization for the Efficient Synthesis of Terpenes and Steroids,"A novel enantioselective palladium-catalyzed dearomative cyclization has been developed for the efficient construction of a series of chiral phenanthrenone derivatives bearing an all-carbon quaternary center. The effectiveness of this method in the synthesis of terpenes and steroids was demonstrated by a highly efficient synthesis of a kaurene intermediate, the facile construction of the skeleton of the anabolic steroid boldenone, and the enantioselective total synthesis of the antimicrobial diterpene natural product (-)-totaradiol.",10.1002/anie.201411817,2015-01-28,0.6621143876926308
Angewandte Chemie International Edition,Asymmetric Total Syntheses of Platensimycin,"There are two ways about it: One route to the potent antibiotic (−)-platensimycin used a catalytic asymmetric cycloisomerization and the other an auxiliary-controlled asymmetric alkylation to set the configuration at a key chiral center (see scheme, TMS=trimethylsilyl). This latter synthesis also used an oxidative dearomatization step to construct a key spirocyclic intermediate en route to the natural product.",10.1002/anie.200700586,2007-04-20,0.6621035401394034
Angewandte Chemie International Edition,An Intramolecular Case of Sharpless Kinetic Resolution: Total Synthesis of Laulimalide,The microtubule-stabilizing antitumor agent laulimalide (1) has been obtained in by new synthetic route. The carbon skeleton was assembled by means of Julia–Kocienski (C16–C17) and Horner–Wadsworth–Emmons (C21–C22) olefinations. Still–Gennari olefination was used for the C2–C3 ring closure. The key step of the synthesis was a regioselective C16–C17 matched Sharpless asymmetric epoxidation.,10.1002/1521-3773(20011015)40:20<3842::aid-anie3842>3.0.co;2-r,2001-10-15,0.6620959827343698
Tetrahedron,An efficient scale up process for synthesis of N-arylpiperazines,,10.1016/j.tetlet.2015.06.003,2015-06-06,0.6620678907146856
Synthesis,"Efficient Synthesis of 4-Amino-2-methoxy-7,8-dihydropyrido[4,3-d]pyrimidin-5-ones: Practical Access to a Novel Chemotype in the Development of DGAT-1 Inhibitors","A practical access to an unprecedented, fused bicyclic 4-amino-2-alkoxy-7,8-dihydropyrido[4,3- d ]pyrimidin-5-one scaffold is developed. The synthesis of the potent inhibitor, 2-{4-[4-amino-2-methoxy-5-oxo-7,8-dihydropyrido[4,3- d ]pyrimidin-6(5 H )-yl]phenyl}-2-methylpropanamide is detailed, with particular emphasis placed on synthetic efficiency and scalability. With the isolation of solid intermediates, the routes described offer clear elements of practicality and facilitate production of the target compound on large scale (>10 g) without chromatography.",10.1055/s-0032-1316756,2012-07-03,0.6620180702171675
Tetrahedron,An efficient route to chiral t-butyl sulfoxides,,10.1016/s0040-4039(01)80475-5,1989-01-01,0.66201733646966
Synlett,"Diastereoselective Synthesis of Tetrahydrofurano[2,3-g]indolizidines and 8-Aminoindolizidines from l-Asparagine","Abstract 8-Aminoindolizidines were synthesized from l-asparagine as the chiral starting material. The key dibenzylamino succinimide intermediate was synthesized in two steps. Three homologs of chiral hydroxy lactams tethered with hydroxyalkenes were synthesized from the succinimide through a sequence involving N-alkylation, cross-olefin metathesis, and hydride reduction. The dibenzylamino group gave stereocontrol of the key N-acyliminium ion cyclization of these hydroxy lactams. 5-Substituted aminoindolizidines were synthesized with high diastereoselectivity at C6. A tandem cyclization of an N-(6-hydroxyhex-3-en-1-yl) γ-hydroxy lactam resulted in the formation of a tetrahydrofurano[2,3-g]indolizidine system.",10.1055/a-1806-6089,2022-03-23,0.6620023626878159
Tetrahedron,An efficient route to the formal total synthesis of A-seco mevinic acid analogues,,10.1016/0040-4039(94)80019-7,1994-10-01,0.6620015605006967
Tetrahedron,An efficient route to the formal total synthesis of A-seco mevinic acid analogues,,10.1016/s0040-4039(00)78393-6,1994-10-10,0.6620015605006967
Organic Process Research & Development,Process Development of a Potent Glucosylceramide Synthase Inhibitor,"An economic, scalable process for the production of glucosylceramide synthase (GCS) inhibitor 7 has been developed. Herein we report a three-step synthesis to aldehyde 4 with high yield and purity that employs the selective cleavage of an endocyclic C–O bond of a THP ether using borane/THF as the key step. This particular methodology has not been used previously from a development standpoint and offers an attractive way towards introducing pentanol side chains. Aldehyde 4 is then coupled with deoxynojirimycin via flow hydrogenation using an H-Cube to safely produce the free base of 7, which is isolated as an MSA salt in 50% overall yield. Herein we discuss the evolution of this process from its original form and the thermodynamics of its associated chemistry.",10.1021/op2001222,2011-06-26,0.6619972189160845
Tetrahedron,"Studies toward the synthesis of salinosporamide A, a potent proteasome inhibitor",,10.1016/j.tetlet.2006.04.070,2006-05-13,0.6619772094112947
Journal of Organic Chemistry,Synthesis of 1-Amino-3-[(dihydroxyboryl)methyl]- cyclobutanecarboxylic Acid as a Potential Therapy Agent,"A novel boronated aminocyclobutanecarboxylic acid (1) was synthesized for potential use in boron neutron capture therapy. Starting from the readily available 3-(bromomethyl)cyclobutanone ketal (4), several synthetic routes to 1 were evaluated. After several unsuccessful attempts with traditional synthetic methods, a novel synthetic strategy to generate the new boronated cyclic amino acid was developed. The tolerance of the hydantoin group to the selenoxide elimination reaction conditions in the preparation of alkenyl compound 7 proved to be the key step in the new strategy.",10.1021/jo048824c,2004-10-27,0.6619663929668389
Tetrahedron,"Practical alternatives for the synthesis of β-iodofurans by 5-endo-dig cyclisations of 3-alkyne-1,2-diols",,10.1016/s0040-4039(01)01112-1,2001-08-01,0.6619367317442784
Tetrahedron,Practical synthesis of acetophenones from phenoltriflates,,10.1016/s0040-4039(00)01935-3,2001-01-01,0.6619367317442784
Tetrahedron,A practical synthesis of β-d-mannopyranosides,,10.1016/s0040-4039(98)01163-0,1998-08-01,0.6619367317442784
Tetrahedron,A practical synthesis of 4′-thioribonucleosides,,10.1016/j.tetlet.2005.11.049,2005-11-29,0.6619367317442784
Tetrahedron,Practical synthesis of unsymmetrical polyamine amides,,10.1016/s0040-4039(97)10542-1,1998-01-01,0.6619367317442784
Tetrahedron,A practical synthesis of (S)-HPMPC,,10.1016/s0040-4039(00)76875-4,1994-05-01,0.6619367317442784
Tetrahedron,A practical synthesis of ()-3-alkenoates,,10.1016/s0040-4039(01)81557-4,1984-01-01,0.6619367317442784
Tetrahedron,A practical synthesis of N-tosylimines of arylaldehydes,,10.1016/s0040-4039(02)02809-5,2003-02-01,0.6619367317442784
Tetrahedron,Practical synthesis of [1-13C]- and [6-13C]-d-galactose,,10.1016/s0040-4039(03)01098-0,2003-06-01,0.6619367317442784
Tetrahedron,A practical synthesis of (+-)-phosphinothricine,,10.1016/s0040-4039(00)81933-4,1983-01-01,0.6619367317442784
Tetrahedron,A practical formal synthesis of camptothecin,,10.1016/j.tetlet.2007.07.017,2007-07-12,0.6619367317442784
Tetrahedron,A practical synthesis of (S)-oxybutynin,,10.1016/s0040-4039(02)02135-4,2002-11-01,0.6619367317442784
Tetrahedron,Practical unequivocal synthesis of phosphatidyl-myo-inositols,,10.1016/s0040-4039(99)02207-8,2000-02-01,0.6619367317442784
European Journal of Organic Chemistry,A Practical Synthesis of 3-Methoxyflavones,Correction,10.1002/(sici)1099-0690(199806)1998:6<1243::aid-ejoc1243>3.0.co;2-o,1998-06-01,0.6619367317442784
Tetrahedron,A practical synthesis of antheridiol,,10.1016/s0040-4039(01)84904-2,1972-01-01,0.6619367317442784
Tetrahedron,Practical synthesis of allylsilanes from 1-benzenesulfonyl-2-trimethylsilylethane,,10.1016/s0040-4039(00)87234-2,1982-01-01,0.6619367317442784
Tetrahedron,"Practical synthesis of d-[1-13C]mannose, l-[1-13C] and l-[6-13C]fucose",,10.1016/j.tetlet.2004.11.073,2004-12-10,0.6619367317442784
Tetrahedron,A practical synthesis of (±)-thienamycin,,10.1016/s0040-4039(00)78606-0,1980-01-01,0.6619367317442784
Tetrahedron,A practical synthesis of (−)-kazusamycin A (revised),,10.1016/j.tetlet.2005.07.029,2005-07-26,0.6619367317442784
Tetrahedron,A practical synthesis of [13C4] N-benzylpiperazine from [13C2] glycine,,10.1016/j.tetlet.2012.05.084,2012-05-26,0.6619367317442784
Organic Letters,Total Synthesis of Psymberin (Irciniastatin A),"A convergent, stereocontrolled total synthesis of psymberin, an architecturally complex marine antitumor agent, has been achieved in 27 steps from the known aldehyde 8. Highlights of this synthesis include a novel and efficient transannular Michael addition/lactone reduction sequence to construct the highly substituted 2,6- trans-tetrahydropyran, a diastereoselective IBr-induced iodocarbonate cyclization to introduce the C17 stereogenic center, and a Diels-Alder/aromatization reaction to install the highly substituted aromatic ring.",10.1021/acs.orglett.9b01113,2019-05-07,0.6619364350747945
Synlett,An Approach to the Synthesis of Tetrahydroisoquinoline Alkaloids by Alkene Hydroamination: Synthesis of Coralydine,"The protoberberine alkaloid coralydine was synthesized in a short sequence by a strategy including an intramolecular alkene hydroamination as the key step, followed by a Pictet–Spengler ­cyclization.",10.1055/s-0033-1339375,2013-08-01,0.6619301019032872
Organic Process Research & Development,"Development of an Efficient Large-Scale Synthesis for a 4<i>H</i>-imidazo[5,1-<i>c</i>][1,4]benzoxazine-3-carboxamide Derivative for Depression and Anxiety","The development and scale-up of an optimized synthesis for a novel drug candidate for depression and anxiety is presented. The updated synthesis represents a convergent and efficient four-stage approach to the API, overcoming high cost of goods (COG), general lack of convergence, and low yield of previous routes. A lower cost of goods resulted from using 3-nitrosalicylaldehyde as a starting material and introducing the expensive side chain (2-methyl-5-(piperazin-1-yl)quinoline) at a later stage. Green chemistry principles were applied when a direct amidation enabled a straightforward conversion of the 4 H -imidazo[5,1- c ][1,4]benzoxazine-3-carboxylate to the corresponding amide in the last step. In addition, the total number of stages was reduced from seven to four, and solvent usage was greatly minimized. The modified synthesis was demonstrated on a kilogram pilot scale, allowing the isolation of the API in 17% overall yield with the required purity.",10.1021/op100103v,2010-06-07,0.6619224685747064
Tetrahedron,"Indium-mediated alkynylation of Baylis–Hillman acetates: a novel route to 1,4-enynes",,10.1016/j.tetlet.2008.08.019,2008-08-13,0.6619199045774428
Tetrahedron,Total synthesis of the didemnins - 1. synthesis of the peptolide ring,,10.1016/0040-4039(88)85084-6,1988-01-01,0.6619118710780915
Organic Letters,Practical Synthesis of a Renin Inhibitor via a Diastereoselective Dieckmann Cyclization,"A scalable synthesis of a potent renin inhibitor (1) is described. The absolute stereochemistry is set via an unprecedented diastereoselective Dieckmann cyclization directed by a remote chiral protecting group. This transformation enables preparation of chiral 1,3-[3.3.1]-diazabicyclononenes by desymmetrization of alkyl-esters, with selectivities ranging from 4 to 17:1.",10.1021/ol102131e,2010-10-14,0.6619087372045428
Synthesis,"Synthesis of the Pyrano[3,2-a]carbazole Alkaloids Koenine, Koenimbine, Koenigine, Koenigicine, and Structural Reassignment of Mukonicine","Using the palladium(II)-catalyzed oxidative cyclization of a diarylamine and the annulation of a dimethylpyran ring by Lewis acid promoted reaction with prenal as key steps, the total syntheses of the 6-oxygenated pyrano[3,2- a ]carbazole alkaloids koenine and koenimbine, and of the 6,7-dioxygenated pyrano[3,2- a ]carbazole alkaloids koenigine and koenigicine (koenimbidine, koenidine) were achieved. Moreover, these studies led to an improved synthetic route to the 2,6-dioxygenated carbazole alkaloid glycozolidol. Mukonicine, originally published as 6,8-dimethoxypyrano[3,2- a ]carbazole, was found to be identical with koenigicine.",10.1055/s-0035-1560359,2015-10-08,0.6618991634532143
Journal of Organic Chemistry,"Enantioselective Synthesis for the (−)-Antipode of the Pyrazinone Marine Alkaloid, Hamacanthin A","A short enantioselective total synthesis for the (-)-antipode of the antifungal marine alkaloid, hamacanthin A, (6R)-3,6-bis(6-bromoindol-3-yl)-5,6-dihydro-2(1H)-pyrazinone, is described. This synthesis proceeds through the coupling of 3-indolyl-alpha-oxoacetyl chloride and 3-indolyl azidoethylamine, followed by intramolecular aza-Wittig type cyclization. A concise and useful approach for the synthesis of (1R)-1-(indol-3-yl)-2-azidoethylamine using the Sharpless asymmetric dihydroxylation reaction followed by stereospecific azidation is also presented.",10.1021/jo010265b,2001-06-12,0.6618647672457809
Journal of Organic Chemistry,Total Synthesis of <i>epi</i>-Trichosetin,The natural 3-decalinoyltetramic acid epi-trichosetin was synthesized in ten steps starting from ( R)-(+)-citronellal using an intramolecular Diels-Alder reaction and a Lacey-Dieckmann cyclization as the key steps. The use of a 2-nitrobenzyl protecting group resulted in an efficient synthetic endgame. The natural product was obtained in 4.1% overall yield.,10.1021/acs.joc.8b02450,2018-11-19,0.6618455040260183
Organic Letters,"Stereoselective Total Synthesis of Formosanol, Tsugacetal, and Methyl β-Conidendral","The first enantioselective total synthesis of aryltetralin lignan acetals, (−)-formosanol, (+)-tsugacetal, (+)-methyl β-conidendral, and their enantiomers have been accomplished on the basis of the Pd-catalyzed asymmetric allylic cycloaddition as a key step. Six stereoisomers of the lignan acetals have been synthesized via a 7–8 step sequence in up to 14% overall yield. The in vitro cytotoxicity against several cancer cells has preliminarily been examined for the obtained six stereoisomers of lignan acetals.",10.1021/acs.orglett.2c03159,2022-10-12,0.6618313715022173
Organic Letters,Total Synthesis of Antitumor Depsipeptide (−)-Doliculide,"[reaction: see text] (-)-Doliculide, a potent antitumor agent, is synthesized stereoselectively in a convergent manner. The key strategy involves a stereoselective synthesis of the polyketide unit and synthesis of the D-tyrosine derivative, followed by assembly of the fragments by an esterification and cycloamidation reaction sequence. The synthesis of the polyketide fragment was achieved by an iterative asymmetric synthesis to install stereoselectively both 1,3-dimethyl groups and the 1,3-diol unit by utilizing asymmetric cyclopropanations and Sharpless asymmetric epoxidations as the key steps.",10.1021/ol0100069,2001-02-01,0.6618058153323589
Tetrahedron,"Asymmetric synthesis of the core of AMPTD, the key amino acid of microsclerodermins F-I",,10.1016/j.tetlet.2009.06.144,2009-07-20,0.6618035659579609
Journal of the American Chemical Society,Approaches to the Synthesis of (±)-Strychnine via the Cobalt-Mediated [2 + 2 + 2] Cycloaddition:  Rapid Assembly of a Classic Framework,"Five synthetic approaches to racemic strychnine (1), with the cobalt-mediated [2 + 2 + 2] cycloaddition of alkynes to indoles as the key step, are described. These include the generation and attempted cyclization of macrocycle 8 and the synthesis of dihydrocarbazoles 15, 22, and 26 and their elaboration to pentacyclic structures via a conjugate addition, dipolar cycloaddition, and propellane-to-spirofused skeletal rearrangement, respectively. Finally, the successful total synthesis of 1 is discussed. The development of a short, highly convergent route (14 steps in the longest linear sequence) is highlighted by the cyclization of enynoylindole 40 with acetylene and the formal intramolecular 1,8-conjugate addition of amine 49 to form pentacycle 50. Numerous attempts toward the formation of the piperidine ring of 1 from vinyl iodide 56 were made and its successful formation via palladium-, nickel-, and radical-mediated processes is described.",10.1021/ja016333t,2001-08-30,0.661795627671753
Organic Letters,Total Synthesis of (±)-Eucophylline. A Free-Radical Approach to the Synthesis of the Azabicyclo[3.3.1]nonane Skeleton,"The first total synthesis of eucophylline was reported in 10 steps and 10% overall yield. The naphthyridine core of eucophylline was prepared through the coupling between a strained azabicyclo[3.3.1]nonan-2-one and a trisubstituted benzonitrile, followed by a cyclization of the corresponding amidine. This coupling reaction was shown to proceed through a stable bicyclic chloroenamine intermediate. The azabicyclo[3.3.1]nonan-2-one skeleton was in turn accessible through a straightforward sequence including a free-radical three-component olefin carbo-oximation as a key step.",10.1021/acs.orglett.5b02218,2015-09-08,0.6617767769450951
Synthesis,Synthesis of the AB-DE Ring System Present in the Alstoscholarine Alkaloids,"A practical protocol is presented for the construction of the AB-DE rings present in (19,20)-(E)- and (19,20)-(Z)-alstoscholarine alkaloids from the commercially available glutamic acid 5-methyl ester, employing only a six-step synthetic sequence. The main features include the synthesis of the alkynylindolizinone core and the use of Sonogashira cross-coupling and base-mediated cyclization to afford a 2-substituted indole without the use of protecting groups.",10.1055/s-0031-1289745,2012-03-15,0.6617651241269646
Synlett,An Efficient EnantioselectiveSynthesis of the 3C Protease Inhibitor (-)-Thysanone,"The enantioselective synthesis of the 3C protease inhibitor (-)-thysanone is described. The key step is the o-toluate anion addition to an α,β-unsaturated δ-lactone. Spectroscopic analysis of the synthetic material confirms the 1R,3S stereochemistry of the natural product. © Georg Thieme Verlag Stuttgart.",10.1055/s-2008-1078590,2008-07-02,0.6617624840996087
Organic Process Research & Development,"The Process Development of a Novel Aldose Reductase Inhibitor, FK366. Part 1. Improvement of Discovery Process and New Syntheses of 1-Substituted Quinazolinediones","This contribution describes part 1 of process development of a novel aldose reductase inhibitor FK366 ( 1 ). The original process applied on a laboratory scale was improved from the safety viewpoint to manufacture materials on 500-L scale suitable for toxicological and pharmacological evaluations. A new process, including regioselective alkylation of silylated quinazolinedione, provided a practical and cost-effective synthesis of FK366 in a dramatically increased yield.",10.1021/op0340661,2003-08-20,0.6617620070646892
Journal of the American Chemical Society,"Enantioselective Total Synthesis of (−)-Acetylaranotin, a Dihydrooxepine Epidithiodiketopiperazine","The first total synthesis of the dihydrooxepine-containing epidithiodiketopiperazine (ETP) (-)-acetylaranotin (1) is reported. The key steps of the synthesis include an enantioselective azomethine ylide (1,3)-dipolar cycloaddition reaction to set the absolute and relative stereochemistry, a rhodium-catalyzed cycloisomerization/chloride elimination sequence to generate the dihydrooxepine moiety, and a stereoretentive diketopiperazine sulfenylation to install the epidisulfide. This synthesis provides access to (-)-1 in 18 steps from inexpensive, commercially available starting materials. We anticipate that the approach described herein will serve as a general strategy for the synthesis of additional members of the dihydrooxepine ETP family.",10.1021/ja209354e,2011-10-24,0.6617363847859213
Journal of Organic Chemistry,A New Total Synthesis of Porritoxin,A concise and efficient total synthesis of the phytotoxin porritoxin is described. The key step of the synthesis is based upon a Parham cyclization methodology which enables the creation of the lactam unit embedded in the title compound framework with the concomitant formation of the tethered hydroxyakyl chain.,10.1021/jo052592f,2006-03-04,0.6617227634603752
Angewandte Chemie International Edition,Total Synthesis of Pederin and Analogues,A ten-step program: The potent cytotoxin pederin and several analogues have been prepared through an efficient route that proceeds in ten steps (longest linear sequence) from isobutyraldehyde. The key transformation is a multicomponent N-acylaminal construction (see scheme) that allows for late-stage fragment coupling and diversification.,10.1002/anie.201006438,2010-12-22,0.6616751619147621
Synthesis,An Efficient and Enantioselective Synthesis of d-Biotin,"All articles of this category An efficient and enantioselective synthesis of d -biotin 1 starting from cis 1,3-dibenzyl-2-imidazo-lidone-4,5-dicarboxylic acid ( 6 ) is described. The key steps are the enantioselective reduction of meso -1,2-dicarboxylic thioanhydride 8 to prepare the (3a S ,6a R )-thiolactone 9 and the introduction of the C 6 side chain at C-2 in 9 via a modified Grignard reaction. This novel synthesis proceeded in six steps to afford 1 with 21% overall yield. d -biotin - vitamin H - ( R )-BINAL-H - enantioselective reduction - Grignard reaction",10.1055/s-2000-8716,2000-01-01,0.6616541170901895
Organic Process Research & Development,Practical Large-Scale Synthesis of the 2-Aminomethylpyrrolidin-4-ylthio-Containing Side Chain of the Novel Carbapenem Antibiotic Doripenem,"The first synthesis using an original procedure and a practical large-scale process using an improved procedure for the synthesis of the N -PNZ-protected 2-aminomethylpyrrolidin-4-ylthio-containing side chain of doripenem hydrate (S-4661), a novel parenteral 1β-methylcarbapenem antibiotic, are described. trans -4-Hydroxy- l -proline ( 4 ) was converted in an efficient process to (2 S,4 S )-4-acetylthio-2-( N -sulfamoyl- tert -butoxycarbonylaminomethyl)-1-(4-nitrobenzyloxycarbonyl)pyrrolidine ( 3 ) in 55−56% overall yield via a six-step sequence, which includes the two alternative routes to intermediate 13 . This process requires no chromatographic purifications, no cryogenic temperatures, no haloalkane solvents, and short operating times and is amenable to a multikilogram-scale preparation. Several kilograms of the side chain 3 were successfully prepared by this process.",10.1021/op0340412,2003-06-06,0.6616434147035349
Organic Letters,Total Synthesis of (±)-Methyl Rishirilide B,"[formula: see text] A regio- and stereospecific total synthesis of (+/-)-methyl rishirilide B (2b), and (alpha)2-macroglobulin inhibitor, is described. A key feature of the synthetic plan was regiospecific construction of a hydroanthracenone intermediate through condensation of a phenylsulfonyl isobenzofuranone with a functionalized 2-cyclohexen-1-one. Introduction of the vicinal trans-hydroxyl groups in the densely functionalized A-ring was accomplished via a novel one-pot procedure that involved oxidation of enolate anions with the Davis reagent.",10.1021/ol9906561,1999-06-04,0.6616194471656636
Organic Letters,An Effective Enantioselective Route to the Platensimycin Core,An efficient enantiocontrolled synthetic pathway to platensimycin has been developed.,10.1021/ol702323s,2007-10-11,0.661614381820758
Tetrahedron,An efficient approach to d-threo-3-hydroxyaspartic acid for the synthesis of novel l-threo-oxazolines as selective blockers of glutamate reversed uptake,,10.1016/j.tetlet.2004.01.081,2004-02-07,0.6616056737437062
Organic Letters,Polysubstituted Piperidines via Iodolactonization: Application to the Asymmetric Synthesis of (+)-Pseudodistomin D,"Conjugate addition of lithium (S)-N-allyl-N-(α-methyl-p-methoxybenzyl)amide to methyl (E,E)-hepta-2,5-dienoate furnished the corresponding β-amino ester. N-Protecting group manipulation, ring-closing metathesis, and ester hydrolysis gave enantiopure [N(1')-tert-butoxycarbonyl-1,2,3,6-tetrahydropyridin-2'-yl]ethanoic acid. Subsequent iodolactonization gave a bicyclic iodolactone scaffold. This key intermediate was elaborated to (+)-pseudodistomin D [in >99% ee and 7% yield over 16 steps from methyl (E,E)-hepta-2,5-dienoate].",10.1021/ol300209s,2012-03-14,0.6615984066743532
Organic Letters,A Novel <i>Cis</i>-Selective Cyclohexanone Annulation as the Key Step of a Total Synthesis of the Sesquiterpene Isoacanthodoral,"Isoacanthodoral (1) is a structurally unique sesquiterpene in that it is a bicyclo[4.4.0]dec-1-ene with a cis- rather than the common trans-junction between the constituting rings. An efficient construction of this motif has been accomplished by a novel cis-selective cyclohexanone annulation, combining the lithium enolate of ester 8, the alpha,beta-unsaturated ester 6, and vinylmagnesium bromide in a single synthetic operation. For completing the total synthesis of 1, a Shapiro-olefination/hydrogenation sequence and a reductive cyanation were employed.",10.1021/ol9018979,2009-09-23,0.6615518194329097
Journal of the American Chemical Society,<i>C</i>-Aryl Glycosides via Tandem Intramolecular Benzyne−Furan Cycloadditions. Total Synthesis of Vineomycinone B<sub>2</sub> Methyl Ester,A triply convergent total synthesis of vineomycinone B2 methyl ester has been achieved by an approach with a longest linear sequence of 16 steps. The synthesis features the use of silicon tethers as disposable linkers to control the regiochemistry in two tandem Diels-Alder reactions of substituted benzynes and glycosyl furans to provide rapid access to the fully intact anthrarufin core of vineomycinone B2 methyl ester.,10.1021/ja0652619,2006-09-28,0.6615501753505306
Journal of Organic Chemistry,Total Synthesis of Halicholactone and Neohalicholactone<sup>1</sup>,"The total synthesis of the marine natural products neohalicholactone ( 1 ) and halicholactone ( 2 ), in enantiomerically pure form, are reported. Key steps in the synthesis of each compound include a cis -selective Wittig reaction, stereoselective cyclopropanation, nine-membered lactone formation using the Yamaguchi method and late-stage stereoselective Cr(II)/Ni(II) mediated coupling of vinyl iodides 39 and 50 with aldehyde 14 . In the case of the neohalicholactone synthesis the two major components which were coupled in this convergent synthesis were each derived from the enantiomers of commercially available malic acid. The synthesis served to confirm the original assignment of absolute configuration which was made by Yamada and Clardy. We also demonstrated, through the preparation of diastereoisomers, that another reported compound closely related to neohalicholactone is likely to be the C-15 epimer 67 .",10.1021/jo962312j,1997-09-01,0.6615365642682367
Organic Letters,First Total Synthesis of Tubulysin B,"The first total synthesis of tubulysin B is described. The aziridine route to tubuphenylalanine (Tup) of the tubulysin D/U-series could not be transferred to the synthesis of tubutyrosine (blue moiety). Therefore, tubutyrosine (Tut) was synthesized by a Wittig olefination/diastereoselective catalytic reduction sequence. Interestingly, the C-2 epimer of tubulysin B has a cytotoxic activity almost identical to the natural diastereomer.",10.1021/ol902320w,2009-11-17,0.6615316368593781
Organic Process Research & Development,Process Development on an Efficient New Convergent Formal Synthesis of MIV-150,"Starting from a known linear route and a proposed convergent route, we have successfully developed a new hybrid convergent route to MIV-150 that takes advantage of the robust chemistry for the preparation of a fluoroketal and the stereospecific Negishi coupling of an iodocyclopropane moiety to a benzene ring. Stereoselective β- and cis- iodination chemistry was developed for the preparation of an enantiomerically pure iodocyclopropanecarboxylate. Following the Negishi coupling, proven chemistry from the linear route was incorporated, thus ensuring a similar high-purity profile for the final active pharmaceutical ingredient (API). In addition, we have prepared and evaluated a series of basic inorganic and organic MIV-150 salts that have drastically increased water solubility over the parent compound.",10.1021/op0341871,2004-03-27,0.6615303349863989
Journal of Organic Chemistry,"Synthesis of an Optically Active, Bicyclic 2-Pyridone Dipeptide Mimetic","The eleven-step preparation of the bicyclic 2-pyridone dipeptide mimetic 1 [(3S)-6-(benzyloxycarbonylamino)-5-oxo-1,2,3,5-tetrahydroindolizine-3-carboxylic acid] in optically active form (60% ee) is described. Key steps in the synthesis of 1 include the osmium-catalyzed asymmetric dihydroxylation of olefin 13 [(6-but-3-enyl-2-methoxypyridin-3-yl)carbamic acid benzyl ester] and the intramolecular cyclization of protected diol 19 [(3'R)-[6-[4'-(tert-butyldimethylsilanyloxy)-3'-hydroxybutyl]-2-methoxypyridin-3-yl]carbamic acid benzyl ester] to afford the pyridinium salt 20 [(3S)-[3-(tert-butyldimethylsilanyloxymethyl)-5-methoxy-2,3-dihydro-1H-indolizin-6-yl]carbamic acid benzyl ester trifuoromethanesulfonic acid salt]. Several alternate methods to prepare olefin 13 are also discussed.",10.1021/jo010712n,2002-01-11,0.6614843268522836
Journal of Organic Chemistry,Asymmetric Total Synthesis of (−)-Linderol A,"The first asymmetric total synthesis of (-)-Linderol A, a potent inhibitor of melanin biosynthesis of cultured B-16 melanoma cells, has been achieved via two key reactions: a diastereoselective [2+2] photocycloaddition of a coumarin-3-carboxylate bearing a chiral auxiliary with 3-methyl-1-butene and a subsequent stereoconvergent transformation of the photoadducts with use of dimethylsulfoxonium methylide to afford a tetrahydrodibenzofuran derivative.",10.1021/jo070682+,2007-06-19,0.6614782196238083
Journal of Organic Chemistry,Asymmetric Total Synthesis of Cladosporin and Isocladosporin,"The first asymmetric total syntheses of cladosporin and isocladosporin were accomplished in 8 steps with 8% overall yield and 10 steps with 26% overall yield, respectively. The relative configuration of isocladosporin was determined via this total synthesis.",10.1021/jo300805n,2012-06-05,0.6614280893757573
Organic Process Research & Development,"A Short Synthesis of the 2-Bromo-<i>N</i>,9-dimethyl-6,7,8,9-tetrahydro-5<i>H</i>-pyrido[2,3-<i>b</i>]indol-6-amine Building Block","A concise synthesis of pharmaceutically useful ( R )- tert -butyl N -(2-bromo-9-methyl-6,7,8,9-tetrahydro-5 H -pyrido[2,3- b ]indol-6-yl)- N -methylcarbamate building block 11 is described. The racemic intermediate 17 was prepared in a single step from 2-bromo-6-(1-methylhydrazinyl)pyridine sulfate salt ( 14 ) and N,3,3-trimethyl-1,5-dioxaspiro[5.5]undecan-9-amine hydrochloride salt ( 16 ). Chiral separation of racemic intermediate 17 by diasteromeric salt recrystallization afforded the diasteromeric salt 18 in 37% yield, which was Boc-protected to afford building block 11 . Thus, the process for the synthesis and chiral separation by diasteromeric salt crystallization allowed the synthesis of chiral building block 11 in kilogram quantities in 18% overall yield.",10.1021/acs.oprd.9b00222,2019-09-20,0.6614004965813189
Organic Process Research & Development,"Efficient Synthesis of (<i>S</i>)-2-(Cyclopentyloxycarbonyl)-amino-8-nonenoic Acid:  Key Building Block for BILN 2061, an HCV NS3 Protease Inhibitor","A new procedure for the practical synthesis of ( S )-2-(cyclopentyloxycarbonyl)amino-8-nonenoic acid, a key building block for BILN 2061, an HCV NS3 protease inhibitor, has been developed. The key step features a kinetic resolution of racemic 2-acetylamino-8-nonenoic acid with acylase I. In addition, the undesired ( R )-2-acetylamino-8-nonenoic acid was recycled after racemization. The procedure was implemented for the production of ( S )-2-(cyclopentyloxycarbonyl)amino-8-nonenoic acid on pilot-plant scale.",10.1021/op0601924,2006-12-20,0.6613907893566748
Organic Process Research & Development,Development of a Scalable Synthetic Route to BMS-986251. Part 1: Synthesis of the Cyclohexane Dicarboxylate Fragment,"The cyclohexane dicarboxylate unit of BMS-986251 ( 1 ), a potent and efficacious RORγt inverse agonist, was synthesized starting from Hagemann’s ester in seven chemical transformations with five isolated intermediates. The synthesis involved an enzymatic kinetic resolution, a two-step telescoped enol tosylation followed by carboxylation using a benign CO surrogate for the installation of the second carboxylate functionality, and a Crabtree catalyst-mediated diastereoselective olefin hydrogenation. This process was successfully demonstrated to produce 3.6 kg of compound 3 .",10.1021/acs.oprd.1c00124,2021-06-15,0.6613905600967664
Tetrahedron,An efficient and practical procedure for Strecker reaction: a highly diastereoselective synthesis of a key intermediate for (+)-biotin,,10.1016/j.tetlet.2004.07.034,2004-07-27,0.6613651805357009
Journal of the American Chemical Society,Total Synthesis of Manzamine A and Related Alkaloids,"Total syntheses of three structurally complex marine natural products, manzamine A, ircinol A, and ircinal A, are reported. The route pivoted on the construction of a late-stage protecting-group-free pentacyclic enol triflate coupling partner, from which all three family members were accessed divergently via palladium-catalyzed reactions. The rapid synthesis of this key pentacyclic enol triflate was achieved by a highly convergent union of five fragments through a stereoselective Michael addition, a three-component nitro-Mannich lactamization cascade, an unprecedented and highly stereoselective reductive nitro-Mannich cyclization cascade, a stereoselective organometallic addition, and a Z-selective alkene ring-closing metathesis. Altogether this chemistry has allowed the shortest synthetic route to date for manzamine A (18-step longest linear sequence) via a late-stage diversification point that is ideal for future manzamine A analogue synthesis.",10.1021/ja308826x,2012-10-07,0.661359318755055
Synthesis,"Efficient Synthesis of a 5α-Reductase Inhibitor, 3-(Tetrazol-5-yl)-3,5-pregnadien-20-one through Allylic Rearrangement of Cyanophosphates","We describe the use of allylic rearrangements of cyanophosphates for the efficient and practical synthesis of 3-(tetrazol-5-yl)-3,5-pregnadien-20-one, which is a potent 5α-reductase inhibitor (IC50: 15.6 nM), from pregnene-3,20-dione in 92% overall yield in four steps.",10.1055/s-0037-1612060,2019-01-29,0.6613488866318257
Organic Letters,A Short Total Synthesis of (+)-Furanomycin,"[reaction: see text] Furanomycin is a Streptomyces metabolite that substitutes for isoleucine in protein translation. We report a concise and modular synthesis starting from the Garner aldehyde and proceeding in seven steps to furanomycin. The key steps include a stereoselective acetylide addition and the Ag+-mediated cyclization of an alpha-allenic alcohol to construct the trans-2,5-dihydrofuran. The efficiency (12% overall yield) and flexibility of the route will provide ample quantities of furanomycin and analogues for protein engineering.",10.1021/ol005569j,2000-02-09,0.6613047682009008
Organic Letters,Total Synthesis of (−)-Galanthamine and (−)-Lycoramine via Catalytic Asymmetric Hydrogenation and Intramolecular Reductive Heck Cyclization,"A synthetic strategy featuring efficient ruthenium-catalyzed asymmetric hydrogenation of racemic α-aryloxy cyclic ketone via dynamic kinetic resolution and palladium-catalyzed intramolecular reductive Heck cyclization has been developed for the asymmetric total synthesis of (-)-galanthamine (20.1%, 12 steps) and (-)-lycoramine (40.2%, 10 steps).",10.1021/ol300913g,2012-05-21,0.6612781977208576
Synthesis,Synthesis of 2-(4-Isopropylthiazol-2-yl)-7-methoxy-8-methylquinolin-4-ol; A Quinoline Building Block for Simeprevir Synthesis,"Two synthetic approaches to the achiral quinoline fragment of simeprevir are described. Both approaches are based on the synthesis of methyl 4-hydroxy-7-methoxy-8-methylquinoline-2-carboxylate, protection of its 4-hydroxyl group, and construction of the thiazole ring from the ester group at the 2-position. The last step is acid deprotection of the 4-hydroxyl protecting group.",10.1055/s-0033-1340679,2014-01-30,0.6612522069874252
Synthesis,Asymmetric Synthesis of (+)-Polyoxamic Acid via an Efficient Organocatalytic Mannich Reaction as the Key Step,A short and efficient stereoselective synthesis of (+)-polyoxamic acid is described using an organocatalytic asymmetric Mannich reaction as the key step. The reaction proceeded in high yield and with excellent selectivity to establish two out of the three stereocenters present in (+)-polyoxamic acid. Additional steps include a diastereoselective reduction and ozonolysis of the furyl ring to generate the corresponding carboxylic acid.,10.1055/s-2006-942413,2006-07-01,0.6612490150009929
Angewandte Chemie International Edition,Total Synthesis and Revised Structure of Biyouyanagin A,"It all adds up: A 12-step total synthesis of biyouyanagin A, an inhibitor of HIV replication, has revealed its structure, rendered it available for biological investigations, and allows the synthesis of analogues. The convergent synthesis involves two cascade sequences and a remarkably selective [2+2] cycloaddition reaction to forge the cyclobutane ring of the target molecule in the ultimate step.",10.1002/anie.200701552,2007-05-27,0.6612322696526133
Tetrahedron,Synthesis of a benzylamidine derived from D-mannose. A potent mannosidase inhibitor,,10.1016/s0040-4039(00)73182-0,1994-03-01,0.6612212906063877
Organic Process Research & Development,Preparation of Phosphonooxymethyl Prodrugs of HIV-1 Attachment Inhibitors,"A practical and scalable synthesis of phosphonooxymethyl prodrugs of HIV-1 attachment inhibitors is described. Starting from azaindoles 1 and 2, this two-step sequence features an efficient alkylation using chloromethyl phosphate 5 and an exceptionally mild deprotection for tert -butyl phosphates. After a salt formation, the API is formed in 82% and 70% overall yield for 3a and 4a, respectively. This chemistry was used to prepare multikilogram quantities of API.",10.1021/op400225q,2013-10-25,0.6611758198200071
Journal of Organic Chemistry,A Practical Synthesis of a γ-Secretase Inhibitor,"A practical and scaleable synthesis of the gamma-secretase inhibitor 1 is reported. The inhibitor consists of a central trisubstituted cyclohexane core with appended propionic acid, 2,5-difluorophenyl, and 4-chlorophenylsulfonyl moieties. Two alternative synthetic strategies, proceeding by way of a common disubstituted cyclohexanone derivative 5, were studied. In the preferred route, conjugate reduction of acrylonitrile derivative 4 with L-Selectride configures the desired relative stereochemistry of the cyclohexane core with >99.9:0.1 dr. A second strategy, based on catalyst-controlled hydrogenation of racemic cyclohexene derivative 2, is more convergent but less diastereoselective (up to 75:25 dr). The common cyclohexanone intermediate 5 was constructed by a regioselective Diels-Alder condensation of a 1,1-disubstituted vinyl sulfone 6 with 2-trimethylsiloxybutadiene.",10.1021/jo070407n,2007-04-28,0.6611737366270348
Synthesis,"Synthesis of (<i>R</i>)- and (<i>S</i>)-4′-Acetoxyolivetol [(<i>R</i>)- and (<i>S</i>)-5-(4′-Acetoxypentyl)-1, 3-benzenediol]: Key Intermediates in the Synthesis of Tetrahydrocannabinol Derivatives","All articles of this category The synthesis of ( R )- and ( S )-4′-acetoxyolivetols, key intermediates in the synthesis of tetrahydrocannabinol derivatives from 3,5-dihydroxybenzoic acid ( 4 ) is described. The 3,5-dihydroxy groups were protected as their tert -butyldimethylsilyl derivatives, and the benzoic acid group was transformed into the benzyl-1,3-dithiane derivative 8 . Treatment of the anion of 8 with the chiral 1,2-epoxypropane gave the dithianyl alcohol 9 , which after acetylation followed by desulfurization and deprotection of the phenolic hydroxyl groups, furnished the desired 4′-acetoxyolivetols ( 2a,b ) in an overall yield of 13 %.",10.1055/s-1994-25509,1994-01-01,0.6611704200057809
Synthesis,"A Novel Three-Step Synthesis of N-(2-Ethylhexyl)-2,7-diiodocarbazole","A new short and reasonably efficient synthesis of N-(2-ethylhexyl)-2,7-diiodocarbazole is presented. 4,4′-Diiodobiphenyl was nitrated and the resulting 4,4′-diiodo-2-nitrobiphenyl was converted via Freeman's modification of the Cadogan ring closure into 2,7-diiodocarbazole, which was then alkylated in the final step. The synthesis represents a significant simplification of the reported five-step procedure.",10.1055/s-0030-1258474,2011-03-14,0.6611702913287199
Organic Letters,Enantioselective Route from Carbohydrates to Cyclooctane Polyols,"[reaction: see text] A synthetic route to select cyclooctane-1,2,3-triols and 1,2,3,4,5-pentaols has been defined. The starting materials are d-glucose or d-arabinose, and the key steps consist of a zirconocene-promoted ring contraction, a [3,3] sigmatropic rearrangement, and more extended functionalization of the resulting cyclooctadienone.",10.1021/ol0474296,2005-01-13,0.6611529349097853
Synthesis,"A New Route to 2,5-Diamino-4,6-dichloropyrimidine, A Key Precursor of 9-Substituted Guanines","All articles of this category An improved synthesis of 2,5-diamino-4,6-dihydroxypyrimidine ( 7 ) is reported. The direct chlorination of 7 provides the shortest (2 step) synthesis of 2,5-diamino-4,6-dichloropyrimidine ( 5 ) reported to date. The procedure described here affords an easy approach to 5 , a key intermediate to various 9-substituted guanines.",10.1055/s-1990-26949,1990-01-01,0.6611254861091341
Tetrahedron,A new synthetic strategy for heteroanthracyclines: Total synthesis of D-ring thiophene analogs of daunomycin,,10.1016/s0040-4039(00)96434-7,1987-01-01,0.6610905571803365
European Journal of Organic Chemistry,Protecting‐Group‐Free Diastereoselective Total Synthesis of (±)‐6‐<i>epi</i>‐Cleistenolide and Chemoenzymatic Synthesis of (–)‐6‐<i>epi</i>‐Cleistenolide,"Abstract A short, efficient, practical, and protecting‐group‐free diastereoselective total synthesis of (±)‐6‐ epi ‐cleistenolide ( 1 ) has been achieved in five steps in 60 % overall yield. The use of a chemoenzymatic approach also gave (–)‐6‐ epi ‐cleistenolide ( 1 ) (&gt;99.9 % ee ). The Achmatowicz reaction, chemoselective oxidation of a hemiacetal, diastereoselective 1,3‐ anti reduction of a β‐hydroxy ketone, and enzymatic resolution of a 1,3‐diol are the key features of this linear total synthesis. The synthetic strategy demonstrated in this paper could be extended for an asymmetric total synthesis of (–)‐cleistenolide ( 1 ) and related biologically active natural products.",10.1002/ejoc.201403123,2014-10-31,0.661078373397931
Tetrahedron,Cyclopentenone synthesis via aldol condensation. Synthesis of a key prostaglandin intermediate,,10.1016/s0040-4039(00)71904-6,1975-01-01,0.6610710488550253
Synthesis,A One-Pot Synthesis of Aurones from Substituted Acetophenones and Benzaldehydes: A Concise Synthesis of Aureusidin,"A one-pot synthesis of aurones from substituted acetophenone and benzaldehyde has been developed on the basis of an improved Algar–Flynn–Oyamada reaction. By using this method, several aurones were prepared in three steps from commercial starting materials. The usefulness of this one-pot strategy was confirmed by a synthesis of aureusidin, an inhibitor of iodothyronine deiodinase, in 41% overall yield. In comparison with a two-step synthesis of this product from the same substrates, the one-pot strategy was more effective, giving a higher yield and requiring fewer and simpler operations.",10.1055/s-0031-1291153,2012-06-21,0.6610401979292518
Synlett,A Bidirectional Synthesis of (+)-Terreusinone,"An efficient, bidirectional synthesis of the photoprotecting dipyrrolobenzoquinone (+)-terreusinone has been accomplished. Key steps include a copper- and amine-free double Sonogashira reaction of an electron-rich 1,4-dibromide with a protected propargylic alcohol followed by pyrrolo[2,3- f ]indole formation by double hydroamination catalyzed by Echavarren’s cationic gold(I) complex. This new route to (+)-terreusinone complements the original synthesis and offers advantages over its predecessor.",10.1055/s-0031-1290693,2012-06-29,0.6609953749252715
Synlett,The Preparation of a Hexacyclic Intermediate for the Synthesis of Strychnos Alkaloids,"All articles of this category The hexacyclic ring system, indolizino[7,8,8a,1- bcd ]-pyrido [1,2,3- lm ]carbazolone 10 has been synthesized in nine steps from the pyrido[3,2,1- jk ]carbazolylethanal 3 . Key steps include the selective reduction of aldchyde 3 , the stereoselective introduction of an allyl unit via the Sakurai reaction and the ozonolysis/dehydrative cyclization to afford bridgehead enamine 10 .",10.1055/s-1992-21338,1992-01-01,0.6609458708029984
Organic Letters,Total Synthesis of (±)-Cordypyridones A and B and Related Epimers,"Efficient racemic synthesis of two antibacterial and antimalarial natural products, cordypyridones A and B, was achieved from inexpensive, commercially available starting materials in an overall yield of 15% (8% and 7%, respectively). This convergent synthesis utilizes a key coupling step of two fragments and the subsequent functional group transformations lead to the target compounds and their 8-epi-analogues.",10.1021/ol9023437,2009-10-29,0.6609165098836384
Organic Letters,"Enabling Asymmetric Synthesis of ABBV-3748, a Corrector Compound for the Treatment of Cystic Fibrosis","ABBV-3748 is a C2 corrector for the treatment of cystic fibrosis profiled among AbbVie’s CFTR portfolio. A decagram-scale enabling asymmetric synthesis is described which addresses numerous shortcomings of the original route. Highlights include an InBr 3 -catalyzed intramolecular hydroarylation reaction that rapidly assembles the chromane core, an exceptionally efficient asymmetric hydrogenation of a primary enamide, and identification of t BuMgCl as a uniquely effective base in a challenging acyl sulfonamide formation.",10.1021/acs.orglett.2c02729,2022-09-30,0.6609063572479701
Organic Letters,Total Synthesis of (−)-Conolutinine,"The first enantioselective synthesis of (-)-conolutinine was achieved in 10 steps. The synthesis featured a catalytic asymmetric bromocyclization of tryptamine to forge the tricycle intermediate. Hydration of an alkene catalyzed by Co(acac)2 was also employed as a key step to diastereoselectively introduce the tertiary alcohol moiety. The absolute configuration of (-)-conolutinine was established to be (2S,5aS,8aS,13aR) based on this asymmetric total synthesis.",10.1021/acs.orglett.5b02046,2015-08-28,0.6608777801618914
Organic Process Research & Development,Transformation of the Manufacturing Process from Discovery to Kilogram Scale for AWZ1066S: A Highly Specific Anti-<i>Wolbachia</i> Drug Candidate for a Short-Course Treatment of Filariasis,"Anti- Wolbachia therapy has been clinically proven to be a safe approach for the treatment of onchocerciasis and lymphatic filariasis. AWZ1066S, a first-in-class highly specific anti- Wolbachia drug candidate developed for a short-course treatment of human filariasis, has advanced into clinical development. An improved, cost-efficient, and scalable process for the manufacture of this clinical candidate is described. Presented herein is the process development work for the active pharmaceutical ingredient (API) and its two key starting materials [2-(trifluoromethyl)-3-pyridyl]methanamine and ( S )-3-methylmorpholine, starting from 2,4-dichloropyrido[2,3- d ]pyrimidine, which is capable of delivering high-purity (>99%) API consistently. The optimized production route was used in the manufacture of the clinical candidate at the kilogram scale to support the ongoing clinical development.",10.1021/acs.oprd.2c00167,2023-01-10,0.6608465694555279
Journal of Organic Chemistry,The First Total Synthesis of Sporiolide A,"The first total synthesis of the natural cytotoxic agent sporiolide A has been accomplished from D-glucal in 16 steps with 6.1% overall yield. Carbohydrates were applied as the chiral templates to manipulate the absolute configuration during the synthesis. Pyridinium chlorochromate (PCC)-promoted transformation of the cyclic enol-ether to lactone, followed by Yamaguchi esterification and intramolecular ring closure metathesis, greatly facilitates synthesis of the target compound.",10.1021/jo0615504,2006-10-01,0.6608444671182389
Organic Process Research & Development,"Pilot-Plant Preparation of an α<sub>v</sub>β<sub>3</sub> Integrin Antagonist. Part 2. Synthesis of <i>N</i>-[2-(5-Hydroxy-4,6-tetrahydropyrimidine)]-3-amino-5-hydroxybenzoic Acid","Studies directed toward the process research and development of a scalable method for preparing tetrahydropyrimidine 2, a key intermediate to the α v β 3 integrin antagonist 1, are described. A linear approach employing 3-amino-5-hydroxybenzoic acid, methyl isothiocyanate, and 1,3-diaminopropan-2-ol as key reagents is detailed. The results of process development research, a successful pilot run, and a production campaign are explained.",10.1021/op049968w,2004-05-12,0.6607972353817869
Journal of Organic Chemistry,Enantiospecific Synthesis of the Phospholipase A<sub>2</sub> Inhibitor (−)-Cinatrin B,"The first enantiospecific synthesis of phospholipase A2 (PLA2) inhibitor (-)-cinatrin B (2) from the D-arabinose derivative 9 is described. The spirolactone system was formed by an Ireland-Claisen rearrangement of the allyl ester 8 followed by hydrolysis and stereoselective iodolactonization. The stereoselectivity of the rearrangement was controlled by the asymmetry in the allylic alcohol fragment. Ester (S)-8 gave the desired rearrangement product 7 and the epimer 13 in high yield as a 73:27 ratio, respectively. The final stereocenter at C2 was introduced via a chelation-controlled addition of the Grignard reagent derived from trimethylsilylacetylene to alpha-hydroxy ketone 6. Transformation of the terminal alkyne into the methyl ester 21 followed by acetal hydrolysis and selective lactol oxidation afforded cinatrin B methyl ester (22). Base hydrolysis and acid-induced relactonization then gave (-)-cinatrin B (2).",10.1021/jo016221k,2002-01-23,0.6607895392834257
Organic Letters,Efforts toward the Total Synthesis of Thuggacin A,"Thuggacin A ( 1 ) is a 17-membered-ring-polyketide antibiotic compound with excellent antituberculosis activity. The total synthesis of thuggacin A has not yet been reported so far. Herein, we disclose our efforts toward the convergent total synthesis of thuggacin A. The key synthetic features include our own one-pot cascade thiazole formation, Evans syn -aldol, Mukaiyama asymmetric aldol reaction, organosilicon-promoted selective alkyne reduction, Shiina macrolactonization, and a nucleophilic ring-opening of epoxide with alkyne to assemble the main framework of thuggacin A. The enantioselective synthesis of trimethylsilyl ethoxymethyl (SEM) derived thuggacin A analogue 2 was achieved in 18 longest linear steps with 2.0% overall yield, and the bioassay of 2 exhibited moderate antituberculosis activity with minimum inhibitory concentration (MIC) of 320 μg/mL.",10.1021/acs.orglett.4c03643,2024-11-15,0.6607775753374097
Organic Process Research & Development,First Safe and Practical Synthesis of 2-Amino-8-hydroxyquinoline,"The first safe and efficient synthesis of the important building block 2-amino-8-hydroxyquinoline ( 1 ) is described. Starting from the readily available N -oxide 3 of the cheap bulk chemical 8-hydroxyquinoline ( 2 ), the target compound is obtained in a two-step one pot procedure in good overall yield (53−66%) and purity (>98%) on a kilogram scale without chromatography.",10.1021/op049944p,2004-06-25,0.6607604708938393
Tetrahedron,"An efficient two-step synthesis of novel 2-amino-substituted pyrazolo[1,5-a][1,3,5]triazines",,10.1016/j.tetlet.2013.01.073,2013-01-24,0.6607371739489727
Organic Process Research & Development,"An Alternative Scalable Process for the Synthesis of 4,6-Dichloropyrimidine-5-carbonitrile","A robust, safe, and scalable process for the synthesis of 4,6-dichloropyrimidine-5-carbonitrile is described. All of the intermediates in the process are storable under normal conditions. Significant process safety evaluation was undertaken in this route, and the highlights of these studies are presented. This scalable and safe synthetic strategy can be applied for multikilogram-scale production.",10.1021/acs.oprd.8b00154,2018-11-13,0.6607189671057141
Journal of the American Chemical Society,Total Synthesis of (−)-<i>N</i>-Methylwelwitindolinone C Isothiocyanate,"We report the first total synthesis of (-)-N-methylwelwitindolinone C isothiocyanate. Our route features a number of key transformations, including an indolyne cyclization to assemble the [4.3.1]-bicyclic scaffold, as well as a late-stage intramolecular nitrene insertion to functionalize the C11 bridgehead carbon en route to the natural product.",10.1021/ja206538k,2011-08-07,0.6607082964414733
Synthesis,Regioselective Synthesis of Linear and Angular Pyridazine Furocoumarins,"With a view to develop a general regioselective route to pyridazine analogues of benzofurocoumarins, the angular compound 3 and the linear compound 9 were synthesized. In both cases the key step in the construction of the fused pyridazine ring was a Diels-Alder reaction of the intermediate dihydrofura-3-ones with 3,6-bis(trifluoromethyl)-1,2,4,5-tetrazine. The furocoumarinone precursor 2 of compound 3 was synthesized in 60% yield by regioselective Fries rearrangement of 7-(chloroacetyloxy)coumarin (1). The benzofuranone 7, the precursor of compound 9, was obtained in a preparatively useful scale and 34% overall yield from ethyl 2,4-dimethoxycinnamate (4) in 3 steps by regioselective Friedel-Crafts chloroacetylation and further cyclization. The coumarin skeleton of compound 9 was completed in the final step by lactonization with BBr3.",10.1055/s-2002-19292,2002-07-26,0.660691853396075
Synlett,"Short synthesis of undecylprodigiosine. A new route to 2,2’-bipyrrolyl-pyrromethene systems",All articles of this category A new convenient synthesis of the immunosuppressive agent undecylprodigiosine 2 is described. The key step of the synthesis is a heteroaromatic cross-coupling between two pyrrole rings in accordance with the Suzuki methodology. Undecylprodigiosine - immunosuppressant - heteroaromatic cross-coupling - Suzuki,10.1055/s-1996-5485,1996-06-01,0.6606808357605951
Synthesis,"A Novel Synthesis of 2,5-Disubstituted 1,3,4-Oxadiazolines by the Regioselective Cyclization of 1,4-Disubstituted Thiosemicarbazides","A novel and efficient route for the regioselective synthesis of 5-aryl-2-[(4-aryl-2-oxo-1,3,2-dioxaphosphinan-2-yl)imino]-2,3-dihydro-1,3,4-oxadiazoles in high yield and purity by the de­sulfurization and cyclization of 1-benzoyl-4-[(4-aryl-2-oxo-1,3,2-dioxaphosphinan-2-yl)thiosemicarbazides under mild conditions is reported. The products are isolated as the trans-isomer only.",10.1055/s-2007-983714,2007-06-01,0.6606519431737787
Tetrahedron,Stereospecific synthesis of a 2β-H-indoloquinolizidinone: Key intermediate in indole alkaloids synthesis,,10.1016/s0040-4039(00)92154-3,1991-01-01,0.6606338565464676
Organic Process Research & Development,Process Improvements in the Production of a Novel Non-Xanthine Adenosine A<sub>1</sub> Receptor Antagonist. A “One-Pot” Horner-Emmons Isomerization Reaction,"Pilot plant scale synthesis of 2-[3-(2-phenylpyrazolo[1,5- a ]pyridin-3-yl-1(6 H )-pyridazin-6-one)-1-cyclohexen-1-yl] acetic acid (FR166124) is described. The process involved efficient isomerization of regioisomers produced in a Horner-Emmons reaction and employed ester exchange and hydrolysis with NaOH in MeOH. Challenges encountered in the final purification stage to afford high quality drug substance in pure crystalline form are also described. Process improvements and optimization of each step permitted elimination of column chromatography, resulting in a straightforward, practical, and cost-effective synthesis of FR166124. These methods were successfully scaled up in a pilot plant to give bulk drug suitable for pharmacological and toxicological evaluation.",10.1021/op990066i,1999-10-13,0.66063290821403
Journal of the American Chemical Society,A Highly Convergent Total Synthesis of Norhalichondrin B,"A new synthetic strategy for the total synthesis of norhalichondrin B featuring a highly convergent approach and our recently disclosed reverse approach for the synthesis of cyclic ether structural motifs is disclosed. Resulting in the shortest route to norhalichondrin B disclosed thus far, the reported total synthesis was achieved through the synthesis of two almost equally complex fragments whose coupling and short elaboration sequence featured an essential epimerization of the C16 stereocenter occurring concurrently with a simple acid-induced deprotection, a tactic based on a prior study along the synthetic route. This unprecedented strategy within the halichondrin family of natural products could find practical application to the synthesis of other more or less complex natural or designed halichondrin analogues.",10.1021/jacs.1c10539,2021-12-01,0.6606221944284252
Tetrahedron,"Effective tuning of the arene and alkanesulfinamides for highly enantioselective synthesis of (S)-4-chlorophenylphenylmethylamine, a key intermediate for antihistamic (S)-cetirizine",,10.1016/s0040-4039(03)00903-1,2003-05-01,0.6605970889790884
Synthesis,"A New Synthetic Route to 3-Oxo-5-phenyl-2,3-dihydropyrazoles",,10.1055/s-1981-29586,1981-01-01,0.6605933227962751
Tetrahedron,Pd-catalyzed route to (±)-podophyllotoxin skeleton. Synthesis of the aryltetralin derivative,,10.1016/s0040-4039(02)00908-5,2002-07-01,0.6605815115498962
Journal of Organic Chemistry,Synthesis of a BC-Dihydrodipyrrin Building Block of Bacteriochlorophyll <i>a</i>,"A strategy for the synthesis of bacteriochlorophyll a relies on joining AD and BC halves that contain the requisite stereochemical configurations of the target macrocycle. The BC half ( 1 ) is a dihydrodipyrrin bearing a dimethoxymethyl group at the 1-position, a β-ketoester at the 8-position, and ( R )-2-methyl and ( R )-3-ethyl substituents in the pyrroline ring. An established route to AD-dihydrodipyrrins (Pd-mediated coupling of a 2-halopyrrole with a chiral 4-pentynoic acid followed by Petasis methenylation, acidic hydrolysis, Paal–Knorr ring closure, and Riley oxidation) proved to be unviable for BC-dihydrodipyrrins given the presence of the β-ketoester unit. A route presented here entails Pd-mediated coupling of a 2-halopyrrole ( 2 ) with (3 R,4 R )-4-ethyl-1,1-dimethoxy-3-methylhex-5-yn-2-one ( 3 ), anti-Markovnikov hydration of the alkyne to give the 1,4-diketone, and Paal–Knorr ring closure. Compound 3 was prepared by Schreiber-modified Nicholas reaction beginning with ( S )-4-isopropyl-3-propionyloxazolidin-2-one and the hexacarbonyldicobalt complex of (±) 3-methoxy-1-(trimethylsilyl)pentyne followed by transformation of the aldehyde derived therefrom to the 1,1-dimethoxymethylcarbonyl motif. The absolute stereochemical configuration of the Schreiber–Nicholas alkylation product was confirmed by single-crystal X-ray diffraction, whereas the BC half ( 1 ) by 1 H NMR spectroscopy showed a J value of 2.9 Hz consistent with the trans -configuration. Taken together, the route provides a key chiral building block for the synthesis of photosynthetic tetrapyrroles and analogues.",10.1021/acs.joc.3c01216,2023-07-20,0.6605705496877673
Organic Letters,Second-Generation Synthesis of Psymberin,"A second-generation formal synthesis of psymberin was successfully developed, incorporating several notable advancements. Central to this approach is a challenging Heck reaction, which effectively unites a sterically demanding aryl moiety with a terminal alkene, showcasing the method’s robustness under these conditions. Additionally, the construction of the isocoumarin scaffold was accomplished through a Pd-mediated cyclization, underscoring the efficiency and precision of this key transformation. Notably, this improved route to De Brabander’s advanced intermediate from the 2,6- trans -tetrahydropyran fragment demonstrates significant advantages over the previous synthesis. The revised method requires seven fewer steps, reducing complexity and enhancing practicality. Moreover, the overall yield has been markedly improved, increasing from 5.9% in the earlier route to 9.3%, reflecting a considerable gain in efficiency. These optimizations highlight the method’s potential for broader applicability in the synthesis of psymberin and related compounds.",10.1021/acs.orglett.5c00396,2025-03-24,0.6605376557075071
Organic Process Research & Development,Unconventional Synthetic Process of Fasudil Hydrochloride: Costly Homopiperazine Was Avoided,"An efficient, robust, and cost-effective synthetic process of fasudil hydrochloride 1 was developed. Starting from readily available ethylenediamine and 5-isoquinoline sulfonyl chloride, the target product 1 was prepared through a six-step reaction, including sulfonamidation, protection, nucleophilic substitution, deprotection, cyclization, and salification. The process afforded 1 in 67.1% overall yield (based on 5-isoquinoline sulfonyl chloride) with 99.94% purity. Compared to the earlier published methodologies, the use of homopiperazine or its derivatives as intermediates was avoided. The salient features of this environmentally friendly synthetic route include easily available starting materials and operational simplicity, which could be suitable for large-scale industrial production.",10.1021/acs.oprd.1c00211,2021-11-22,0.6605155844670909
Organic Process Research & Development,"First Scale-Up Synthesis of WAY-262398, a Novel, Dual-Acting SSRI/5HT1a Antagonist","An alternative synthesis of WAY-262398, 1, a novel, dual-acting SSRI/5-HT 1A antagonist, has been developed. The target compound was initially synthesized as a part of diastereomeric mixture which was separated by chiral preparative HPLC. The new route was designed around intermediates suitable for chiral resolution and/or chiral reduction of a suitable intermediate. Both processes had to be employed to achieve the target optical purity.",10.1021/op8002085,2008-12-19,0.6605089345123172
Organic Letters,Total Synthesis of the Neotropical Poison-Frog Alkaloid (−)-205B,"[reaction: see text]. A stereocontrolled total synthesis of the neotropical poison-frog alkaloid (-)-205B (1) has been achieved, employing a dithiane three-component linchpin coupling, a one-pot sequential construction of the embedded indolizidine ring, and ring-closing metathesis (RCM) to arrive at the novel 8b-azaacenaphthylene ring system comprising the alkaloid. The synthesis proceeded with a longest linear sequence of 19 steps, affording (-)-1 in 5.6% overall yield.",10.1021/ol0510264,2005-06-11,0.6604885005106164
Synthesis,Stereoselective Total Synthesis of Unnatural (+)-Anisomycin,"Stereoselective total synthesis of unnatural (+)-anisomycin from d -glucose has been achieved with an overall yield of 23%. The key synthetic features are regioselective opening of an epoxide, azidation of the resulting alcohol, and finally one-pot hydrogenation leading to cyclization to the pyrrolidine ring in a single step.",10.1055/s-0035-1561365,2016-02-10,0.6604883850377214
Tetrahedron,"Efficient synthesis from d-lyxonolactone of 2-acetamido-1,4-imino-1,2,4-trideoxy-l-arabinitol LABNAc, a potent pyrrolidine inhibitor of hexosaminidases",,10.1016/j.tetlet.2007.04.041,2007-04-15,0.6604829519737484
Journal of the American Chemical Society,Total Synthesis of the Dihydrooxepine-Spiroisoxazoline Natural Product Psammaplysin A,We report a general synthetic entry to dihydrooxepine-spiroisoxazoline (DOSI) natural products that culminated in the first racemic total synthesis of psammaplysin A. For the synthesis of the unique spirocyclic fragment we employed a strategy that features two key transformations: (1) a diastereoselective Henry reaction/cyclization sequence to access the C7 hydroxylated isoxazoline scaffold in one step and (2) a regioselective Baeyer-Villiger ring expansion to install the fully substituted dihydrooxepine and avoid the risk of a previously observed oxepine-arene oxide rearrangement. The overall synthesis proceeds in 13 steps from an inexpensive starting material.,10.1021/jacs.2c10010,2022-10-21,0.6604749470382519
Synlett,"Total Synthesis of Mniopetals A, B, C and D","A total synthesis of the mniopetals A, B, C and D is described. Key steps are a Sharpless asymmetric dihydroxylation and a selective esterification of an equatorial hydroxy group vicinal to an axial hydroxy function.",10.1055/s-0033-1339172,2013-06-10,0.6604744314285635
Chemical Science,Total synthesis of diazonamide A,"A total synthesis of the marine natural product diazonamide A (1) has been accomplished. This work features a highly stereoselective synthesis of the C(10) quaternary center and the central furanoindoline core enabled by an iminium-catalyzed alkylation-cyclization cascade. Additionally, a magnesium-mediated intramolecular macroaldolization and a palladium-catalyzed tandem borylation/annulation were developed to enable the closure of the two 12-membered macrocycles of diazonamide A. This synthesis involves 20 steps in its longest linear sequence and proceeds in 1.8% overall yield.",10.1039/c0sc00577k,2010-12-24,0.6604477989589065
Synthesis,"A Convenient Synthesis of 2,3,4,5-Functionalised Thieno[2,3-<i>b</i>]thiophenes","A two steps simple synthesis of 2,3,4,5-functionalised thieno[2,3-b]thiophenes 2-6 from ketene dimethylthioacetals is described.",10.1055/s-2003-38080,2003-01-01,0.6604457685438253
Journal of Organic Chemistry,Total Synthesis of the Antitumor Antibiotic (±)-Streptonigrin: First- and Second-Generation Routes for de Novo Pyridine Formation Using Ring-Closing Metathesis,"The total synthesis of (±)-streptonigrin, a potent tetracyclic aminoquinoline-5,8-dione antitumor antibiotic that reached phase II clinical trials in the 1970s, is described. Two routes to construct a key pentasubstituted pyridine fragment are depicted, both relying on ring-closing metathesis but differing in the substitution and complexity of the precursor to cyclization. Both routes are short and high yielding, with the second-generation approach ultimately furnishing (±)-streptonigrin in 14 linear steps and 11% overall yield from inexpensive ethyl glyoxalate. This synthesis will allow for the design and creation of druglike late-stage natural product analogues to address pharmacological limitations. Furthermore, assessment of a number of chiral ligands in a challenging asymmetric Suzuki-Miyaura cross-coupling reaction has enabled enantioenriched (up to 42% ee) synthetic streptonigrin intermediates to be prepared for the first time.",10.1021/jo402388f,2013-12-12,0.6604333098805099
Organic Process Research & Development,An Improved and Scalable Process for Celecoxib: A Selective Cyclooxygenase-2 Inhibitor,"An improved, scalable and commercially viable process is developed for an active pharmaceutical ingredient, celecoxib.",10.1021/op800158w,2008-11-26,0.6604238940309224
Journal of the American Chemical Society,Enantioselective Total Synthesis of Taxol,"Enantioselective total synthesis of taxol has been accomplished. Coupling reaction of the optically\npure A-ring hydroxy aldehyde with the aromatic C-ring fragment followed by Lewis acid mediated eight-membered B-ring cyclization gave the desired ABC endo-tricarbocycle. The C-ring moiety of this product\nwas reduced under Birch conditions to the cyclohexadiene derivative, which was oxygenated by singlet oxygen\nfrom the convex β-face to give the C4β,C7β-diol stereoselectively. For introduction of the C19-methyl, the\ncyclopropyl ketone was prepared via cyclopropanation of the C-ring allylic alcohol or conjugate addition of\na cyano group to the C-ring enone. Reductive cleavage of the cyclopropane ring followed by isomerization of\nthe resulting enol to the corresponding ketone gave the crucial synthetic intermediate containing the C19-methyl group. Regioselective transformation of three hydroxyl groups of this intermediate, conversion of the\nC4-carbonyl group to the allyl chloride, and introduction of the C10-oxygen functionality afforded a precursor\nfor D-ring construction. Dihydroxylation of the allyl chloride moiety followed by basic treatment of the resulting\ndiol gave a fully functionalized taxol skeleton. Functional group manipulation of this product including\nattachment of the C13 side chain provided (−)-taxol.",10.1021/ja9824932,1998-12-01,0.6604044699854206
Journal of the American Chemical Society,"Total Syntheses of (+)-Waixenicin A, (+)-9-Deacetoxy-14,15-deepoxyxeniculin, and (−)-Xeniafaraunol A","High Resolution Image Download MS PowerPoint Slide The first asymmetric total synthesis of the Xenia diterpenoid waixenicin A, a potent and highly selective TRPM7 inhibitor, is reported. The characteristic trans -fused oxabicyclo[7.4.0]tridecane ring system was constructed via a diastereoselective conjugate addition/trapping sequence, followed by an intramolecular alkylation to forge the 9-membered ring. While a β-keto sulfone motif enabled efficient ring-closure, the subsequent radical desulfonylation suffered from ( E )/( Z )-isomerization of the C7/C8-alkene. Conducting the sequence with a trimethylsilylethyl ester allowed for a fluoride-mediated decarboxylation that proceeded without detectable isomerization. The acid-labile enol acetal of the delicate dihydropyran core was introduced at an early stage and temporarily deactivated by a triflate function. The latter was critical for the introduction of the side chain. Diverting from a common late-stage intermediate provided access to waixenicin A and 9-deacetoxy-14,15-deepoxyxeniculin. A high-yielding base-mediated dihydropyran-cyclohexene rearrangement of 9-deacetoxy-14,15-deepoxyxeniculin led to xeniafaraunol A in one step.",10.1021/jacs.3c03366,2023-05-16,0.6603896783964617
Organic Letters,"Synthesis of 2,3- and 3,4-Methanoamino Acid Equivalents with Stereochemical Diversity and Their Conversion into the Tripeptide Proteasome Inhibitor Belactosin A and Its Highly Potent <i>Cis</i>-Cyclopropane Stereoisomer","A series of chiral 2,3- and 3,4-methanoamino acid equivalents of stereochemical diversity were designed and synthesized from our chiral cyclopropane units, using a diastereoselective Grignard addition with ( R)- or ( S)- t-butanesulfinyl imines as the key step. These equivalents were converted into the proteasome inhibitor belactosin A and its cis-cyclopropane stereoisomer. The unnatural cis-isomer was shown to be more than twice as potent as belactosin A as a proteasome inhibitor.",10.1021/ol8013304,2008-07-19,0.6603735971948062
Organic Process Research & Development,Sulfone Displacement Approach for Large-Scale Synthesis of 4-Chloro-<i>N</i>-(1-methyl-1<i>H</i>-pyrazol-4-yl)pyrimidin-2-amine,"Route evaluation, process development, and large-scale manufacturing of 4-chloro- N -(1-methyl-1 H -pyrazol-4-yl)pyrimidin-2-amine ( 1 ) are described. The improved route consists of two linear chemical steps: oxidation of 4-chloro-2-(methylthio)pyrimidine ( 11 ) to 4-chloro-2-(methylsulfonyl)pyrimidine ( 7 ) and displacement of the sulfonyl with N -(1-methyl-1 H -pyrazol-4-yl)formamide ( 10 ) under basic conditions followed by in situ hydrolysis of the N -formyl intermediate to deliver compound 1 . N -(1-Methyl-1 H -pyrazol-4-yl)formamide ( 10 ) was readily prepared from 1-methyl-1 H -pyrazol-4-amine ( 4 ) via reaction with formic acid. The route allows for large-scale production of 4-chloro- N -(1-methyl-1 H -pyrazol-4-yl)pyrimidin-2-amine ( 1 ). Density functional theory (DFT) calculations were carried out to better understand the observed reactivity and selectivity.",10.1021/acs.oprd.1c00314,2021-12-30,0.6603712009551791
Reaction Chemistry & Engineering,Practical and scalable one-pot synthesis of arbekacin,An efficient and scalable one-pot production process was developed to prepare arbekacin from dibekacin.,10.1039/d3re00598d,2024-01-01,0.6603697786394546
Synlett,"Concise Synthesis of (2S,3R)-3-Hydroxy-2-phenylpiperidine: An Advanced Key Intermediate of Human Non-Peptide NK-1 Receptor Antagonists","The rapid, high-yielding synthesis of (2S,3R)-3-hydroxy-2-phenylpiperidine, a known advanced key intermediate of some non-peptide human NK-1 receptor antagonists such as (+)-CP-99,994, (+)-CP-122,721 and (+)-LP-733,060, is reported. This synthesis involves the stereoselective addition of racemic 3-(methoxymethoxy)allenylzinc bromide to enantiopure (R S,E)-N-2-benzylidene-2-methylpropane-2-sulfinamide and a ring-closing metathesis reaction as the key steps. Following this procedure, (2S,3R)-3-hydroxy-2-phenylpiperidine is obtained in seven steps in 56.2% overall yield.",10.1055/s-0029-1218308,2009-10-23,0.6603421223959093
Journal of Organic Chemistry,A Novel Synthesis of Racemic and Enantiomeric Forms of Prostaglandin B<sub>1</sub>Methyl Ester,"3-(Dimethoxyphosphorylmethyl)cyclopent-2-enone was converted into (+/-)-prostaglandin B1 methyl ester in two steps involving regioselective alkylation at C(2) with methyl 7-iodoheptanoate and subsequent Horner-Wittig reaction with dimer of 2-hydroxyheptanal (42% overall yield). The use of (R)- and (S)-2-(tert-butyldimethylsilyloxy)heptanal for the Horner olefination reaction gave, after deprotection of the hydroxy group, the enantiopure forms of the title compound in 28% overall yield.",10.1021/jo0001129,2000-07-29,0.6603380724369049
Synlett,Total Synthesis of (-)-Balanol,"All articles of this category The total synthesis of (-)-balanol, a potent protein kinase C inhibitor, is described. The synthesis includes a radical cyclization approach to the hexahydroazepine-containing fragment and a biomimetic route to the benzophenone fragment. (-)-balanol - total synthesis - radical cyclization - oxime ether - chrysophanic acid",10.1055/s-1997-3236,1997-05-01,0.6603374142158079
Tetrahedron,"Asymmetric hydrogenation of tetrahydropyrazines: Synthesis of (S)-piperazine-2-tert-butylcarboxamide, an intermediate in the preparation of the HIV protease inhibitor indinavir",,10.1016/0040-4039(95)01345-i,1995-09-01,0.6603318579648219
Angewandte Chemie International Edition,Total Synthesis of Cribrostatin 6,"Fast and furious: Cribrostatin 6, an antimicrobial and antineoplastic agent, was the target of a total synthesis where the longest linear sequence was only four steps. The key step involves a tandem 4pi electrocyclic ring opening, radical cyclization, and homolytic aromatic substitution sequence to afford the tricyclic core of the natural product.",10.1002/anie.200806269,2009-02-23,0.6603243053686081
Angewandte Chemie International Edition,"An Efficient and General Method for the Synthesis of α,ω‐Difunctional Reduced Polypropionates by Zr‐Catalyzed Asymmetric Carboalumination: Synthesis of the Scyphostatin Side Chain","A decrease in the number of linear synthetic steps and an increase in efficiency have been realized in the synthesis of the side chain of scyphostatin. An efficient and selective synthesis of α,ω-difunctional reduced polypropionates from methyl 3-hydroxy-2-methylpropionate through the use of a Zr-catalyzed asymmetric carboalumination has been developed (see scheme, TBS=tert-butyldimethylsilyl).",10.1002/anie.200353429,2004-05-19,0.6603170408894229
Synlett,Novel Synthetic Industrial Approach for Efficient Synthesis of Baclofen through C–C Bond Formation,"Abstract Baclofen is an active pharmaceutical ingredient used for the treatment of muscle spasticity. We describe our efforts to develop a novel synthetic approach through C–C bond formation and a cost-effective route to baclofen. The synthesis involved a two-step approach through C–C bond formation using the extensively and commercially available starting material 4-chlorobenzyl cyanide with chloroacetic acid as a reagent in an aprotic solvent, followed by reduction of the nitrile functional group. The synthetic route to baclofen has been demonstrated to be commercially viable, cost-effective, and environmentally friendly. Execution of the developed process led to the isolation of (+)-baclofen in an overall yield of 60% at a multikilogram scale with &gt;99.5% HPLC purity. This article also discusses the cost-effectiveness of the process, the impurity profiling, and the product quality.",10.1055/a-2234-3622,2023-12-21,0.6603163268371127
Journal of Organic Chemistry,Synthesis of a C1−C21 Subunit of the Protein Phosphatase Inhibitor Tautomycin:  A Formal Total Synthesis,"The synthesis of a C1-C21 subunit of tautomycin is described. The convergent route employs enantioenriched allenylstannane and zinc reagents derived from (S)-3-butyn-2-ol methanesulfonate. These reagents react with appropriate aldehyde segments to yield syn and anti adducts with high diastereoselectivity. The derived lithioalkynes are joined stepwise to a CO equivalent, (MeONMe)2C=O, to afford an intermediate ketone which is converted to the core spiroketal moiety of tautomycin upon acid treatment. Chain elongation by another addition of the aforementioned allenylzinc reagent to a spiroketal aldehyde proceeds with high diastereoselectivity to install the remaining stereocenters. The resulting homopropargylic alcohol adduct is converted to a methyl ketone through intramolecular hydrosilylation of the alkyne and Tamao oxidation of the derived five-membered siloxane. This ketone proved identical to an intermediate employed by Chamberlin in a prior total synthesis of tautomycin.",10.1021/jo0056951,2001-01-24,0.6603074380571694
Organic Process Research & Development,Development of a Multikilogram Synthesis of a Chiral Epoxide Precursor to a CCR1 Antagonist. Use of in Situ Monitoring for Informed Optimisation via Fragile Intermediates,"The optimisation and scale up of a manufacturing route to a key intermediate, acetic acid 4-acetylamino-3-(2-methyl-oxiranylmethoxy)phenyl ester ( 2 ), utilising a S N Ar coupling, the hydrogenation of a nitro moiety and the conversion of a chiral acetonide into a chiral epoxide is described along with other routes to access intermediate 2 including the chemoselective reduction of a nitro moiety in the presence of an epoxide.",10.1021/op900172t,2009-11-10,0.660278854495543
Organic Letters,Total Synthesis of the Immunosupressant (−)-Pironetin (PA48153C),"[reaction: see text]. Total synthesis of the immunosuppresant pironetin has been achieved by a synthetic route in which the connections between starting materials and the desired structure are readily discerned. Key steps include a diastereoselective Lewis acid mediated crotylstannane aldehyde addition, a highly selective Lewis acid promoted Mukaiyama aldol reaction, an anti-selective SmI2 reduction of a beta-hydroxyketone, and finally a lactone annulation reaction.",10.1021/ol015531m,2001-02-14,0.6602736381235585
Tetrahedron,"A new and efficient synthetic route toward 3,4-alkylenedioxypyrrole (XDOP) derivatives via Mitsunobu chemistry",,10.1016/j.tetlet.2006.03.086,2006-04-18,0.6602659187990183
Journal of the American Chemical Society,Total Synthesis of RK-397,An enantioselective synthesis of the polyene macrolide RK-397 is described. The use of the same eight-carbon building block twice for the construction of the polyol chain allowed for a highly convergent synthesis. The synthesis highlights stereoselective vinylogous aldol addition using a chiral bisphosphoramide as well as a sequential palladium-catalyzed cross-coupling reaction for the preparation of key fragments.,10.1021/ja052226d,2005-06-01,0.6602543062362959
Journal of Organic Chemistry,Total Synthesis of Dehydrodidemnin B. Use of Uronium and Phosphonium Salt Coupling Reagents in Peptide Synthesis in Solution,"New total syntheses of didemnin A and of dehydrodidemnin B are described. The latter didemnin has the highest antiproliferative activity of all members of this family of macrocyclic depsipeptides. It was produced on coupling the side chain Pyr-Pro-OH to didemnin A, which was itself synthesized by two novel routes. One of these was based on the elaboration of a linear heptadepsipeptide incorporating the first amino acid of the didemnin side chain, (R)-N(Me)-Leu. Deprotection of the amino and carboxyl terminii of this linear precursor followed by macrocyclization gave a protected derivative of didemnin A. The second route involved synthesis of the Boc-protected didemnin macrocycle from a linear hexadepsipeptide lacking (R)-N(Me)-Leu. Removal of the Boc group from the macrocycle followed by its coupling with Boc-(R)-N(Me)-Leu-OH then gave Boc-didemnin A. The overall yield was much higher for the second strategy (27% compared to 4% for the first synthesis), but both allowed synthetic didemnin A, identical with a natural sample, to be prepared. Extensive use was made of phosphonium and uronium salt-based coupling reagents, such as BOP, PyBrOP, PyAOP, HBTU, and HATU for the formation of both the secondary and tertiary amide bonds present in these complex depsipeptides.",10.1021/jo961932h,1997-01-01,0.660248944030203
Organic Process Research & Development,"Synthesis of a <i>cis</i> 2,5-Disubstituted Morpholine by De-epimerization: Application to the Multigram Scale Synthesis of a Mineralocorticoid Antagonist","A convergent route to multigram quantities of a mineralocorticoid antagonist 3 is described. Starting from ( R )-phenylglycinol, the synthesis of cis 2,5-morpholine 2 is accomplished utilizing a de-epimerization to install the second stereogenic center. The multigram synthesis of 3 was completed through a sequence of an S N Ar reaction, Dakin oxidation, alkylation, and cyclization to provide a crystalline solid.",10.1021/op400101p,2013-05-20,0.6602391697533934
Organic Letters,Heck Arylation of Endocyclic Enecarbamates with Diazonium Salts. Improvements and a Concise Enantioselective Synthesis of (−)-Codonopsinine,Total enantioselective synthesis of the natural (-)-codonopsinine was accomplished in seven steps with an overall yield of approximately 16% starting from the five-membered endocyclic enecarbamate 4. The total synthesis features a highly efficient and stereoselective Heck arylation of endocyclic enecarbamate 4 with p-methoxybenzenediazonium tetrafluoroborate and a stereoselective epoxidation/epoxide opening sequence as key steps.,10.1021/ol005762d,2000-09-07,0.6602353294795497
Organic Letters,New Synthetic Routes to (+)-Uleine and (−)-Tubifolidine: General Approach to 2-Azabicyclo[3.3.1]nonane Indole Alkaloids,"Novel asymmetric synthetic routes to (+)-uleine and (-)-tubifolidine are reported herein. The regioselective formation of enol triflates from 2-azabicyclo[3.3.1]nonane ketones followed by indolizations of the resultant ene-hydrazides allowed the efficient construction of key indole intermediates, facilitating the total synthesis of the target natural alkaloids.",10.1021/acs.orglett.0c00912,2020-04-13,0.6602291340667942
Tetrahedron,A novel synthesis of (+)-methyl 6-bromopenicillinate,,10.1016/s0040-4039(01)97615-4,1971-01-01,0.6602258407664342
Tetrahedron,Novel synthesis of methyl caronate,,10.1016/s0040-4039(00)84509-8,1986-01-01,0.6602258407664342
Tetrahedron,A novel synthesis of methyl dl-jasmonate,,10.1016/s0040-4039(01)91433-9,1978-01-01,0.6602258407664342
Journal of Organic Chemistry,Synthesis of Dibenzazepinones by Palladium-Catalyzed Intramolecular Arylation of <i>o</i>-(2′-Bromophenyl)anilide Enolates,"A new approach for the convenient synthesis of dibenzazepinones is reported. The key step is the formation of the seven-membered ring through palladium-catalyzed intramolecular arylation of an anilide enolate. The reactions were completed in 10 min at 100 °C with moderate to excellent yields. Aminodibenzazepinone 1, the core structure in the γ-secretase inhibitor LY411575, can be prepared in five steps from 2-bromophenylboronic acid and 2-iodoaniline in 60% overall yield. The synthesis reported here compares favorably with presently available approaches to this interesting ring system.",10.1021/jo101137r,2010-09-07,0.6602228939769468
Journal of Organic Chemistry,Diastereoselective Formal Synthesis of Polycyclic Meroterpenoid (±)-Cochlearol A,A formal synthesis of (±)-cochlearol A was accomplished. The synthesis features Suzuki coupling and Friedel-Crafts cyclization as a convergent strategy to the functionalized tetralone ring and an intramolecular construction of the C/D ring involving sequential epoxide formation/acetal formation.,10.1021/acs.joc.1c00205,2021-03-22,0.6602210751757863
Organic Letters,Synthesis of the C1–C26 Hexacyclic Subunit of Pectenotoxin 2,Synthesis of the C1-C26 hexacyclic subunit of pectenotoxin-2 (PTX-2) is described that features a stereoselective annulation to generate the C-ring by triple asymmetric Nozaki-Hiyama-Kishi coupling followed by oxidative cyclization. Preparation of the C1-C14 AB spriroketal-containing subunit employs a recently developed metallacycle-mediated reductive cross-coupling between a TMS-alkyne and a terminal alkene.,10.1021/ol302751b,2012-10-26,0.6602209859063792
Organic Letters,Nodulisporic Acid A Synthetic Studies. 1. Overall Strategy and Construction of a Western Hemisphere Subtarget,"In this, the first of two Letters, we outline our overall strategy for the construction of (+)-nodulisporic acid A (1), a representative member of a new class of indole diterpenes. In addition, we describe the efficient assembly of (-)-6, an advanced western hemisphere subtarget, comprising the ABC rings of (+)-nodulisporic acid A (1). The synthesis proceeded in 9% overall yield (longest linear sequence, 11 steps), exploiting a Shibasaki-Mori tandem transmetalation-cyclization to construct ring B. [reaction: see text]",10.1021/ol0168871,2001-11-01,0.6602089899975664
Tetrahedron,A new route to 1-phenylnaphthalenes by cycloaddition: a simple and selective synthesis of some naphthalene lignan lactones,,10.1016/s0040-4039(00)98577-0,1985-01-01,0.6601954037358423
Journal of Organic Chemistry,Practical Synthesis of Chiral Ligands for Catalytic Enantioselective Cyanosilylation of Ketones and Ketoimines,"A practical synthesis of chiral ligands that are useful for catalytic enantioselective cyanosilylation of ketones and ketoimines is described. Compared with the previous synthetic route, the number of total steps is decreased and the total yield is greatly improved. Furthermore, both (+)- and (-)-ligands are readily available by this new synthetic route.",10.1021/jo049258o,2004-07-24,0.6601927611104187
Journal of the American Chemical Society,Total Synthesis of (+)-Pierisketone B,"We report herein the first total synthesis of (+)-pierisketone B, a bioactive diterpene that possesses a unique tetracyclic 7/5/6/5 carbocyclic framework that is punctuated with numerous stereocenters, two of which are quaternary and five of which are contiguous. The synthesis features an unusual Pauson Khand cyclization to generate the bridged tricyclic core. Creation of the requisite cis -fused hydrindanone moiety was achieved by hydroxyl directed hydrogenation of an allylic alcohol, and the A-ring of the natural product was formed by a Mukaiyama aldol reaction followed by a cyclization involving addition of a vinyl anion to a proximal ketone group. The resulting tetracyclic intermediate was then elaborated in six steps to complete the first total synthesis of (+)-pierisketone B in a longest linear sequence of 20 steps from (−)-linalool.",10.1021/jacs.5c08617,2025-08-06,0.6601596219204946
Tetrahedron,Synthesis of (purin-6-yl)methylphosphonate bases and nucleosides,,10.1016/j.tetlet.2010.02.167,2010-03-04,0.6601522384402796
Tetrahedron,Synthesis of monofluorinated 1-(naphthalen-1-yl)piperazines,,10.1016/j.tetlet.2007.05.156,2007-06-04,0.6601522384402796
Tetrahedron,Synthesis of N2-(2-aminofluoren-3-yl) adducts of 2′-deoxyguanosine,,10.1016/s0040-4039(98)02502-7,1999-01-01,0.6601522384402796
Angewandte Chemie International Edition,Total Synthesis of Pseudolaric Acid A,The antiangiogenic and cytotoxic natural product pseudolaric acid A ((−)-1) has been obtained by a 26-step synthetic route. This enantioselective synthesis employed an intramolecular carbene cyclization cycloaddition cascade reaction as the key step to construct the carbocyclic framework. PMB=para-methoxybenzyl.,10.1002/anie.200602056,2006-08-15,0.6601510838885511
Organic Letters,Stereoselective Allylstannane Addition for a Convergent Synthesis of a Complex Molecule,"A convergent methodology with 13 lineal steps for the synthesis of phormidolides B and C macrocyclic core is described. Stereoselective formation of the tetrahydrofuran (THF) core was achieved using a stereocontrolled allylation reaction. The key step of the synthesis is a (Z)-1,5-anti stereoselective allylstannane addition where a new stereocenter and a trisubstituted double bond are formed simultaneously. Finally, Shiina macrolactonization conditions improved the yield of the final cyclization.",10.1021/acs.orglett.5b03252,2015-12-07,0.6601464001335863
Organic Process Research & Development,Comprehensive Synthetic Route Redesign of AZD5991: A High-Complexity Atropisomeric Macrocycle,"We describe our approach to the total synthesis of AZD5991 ( 1 ) from a process development perspective through the complete redesign of our synthetic strategy from the ground up. The size and complexity of small-molecule therapeutic targets have continued to increase over recent decades. One such example, 1, is arguably the most complex active pharmaceutical ingredient (API) in AstraZeneca’s small molecule development portfolio to date and poses formidable synthetic challenges. The previous racemic synthesis of 1 was sufficient to supply early clinical activities; however, the route was not deemed commercially viable and had significant environmental challenges. The identification of a long-term sustainable route was therefore critical to enable the robust manufacture of drug substance for later clinical activities and launch. We report exploration of asymmetric approaches toward the atropisomeric core, new routes toward each of the four heterocyclic building blocks, including a divergent pyrazole functionalization, and final assembly in a scalable and controlled macrocyclization process. These improvements resulted in a 49% reduction in step count and 95% reduction in projected waste generation.",10.1021/acs.oprd.4c00524,2025-02-25,0.6601427481026532
Tetrahedron,"Efficient synthesis of (R)-ochratoxin alpha, the key precursor to the mycotoxin ochratoxin A",,10.1016/j.tetlet.2012.11.123,2012-12-04,0.6601310605228241
Organic Letters,Expedient Construction of the Ziegler Intermediate Useful for the Synthesis of Forskolin via Consecutive Rearrangements,"The Ziegler intermediate, useful for the total synthesis of forskolin, was synthesized in 10 reaction steps starting from commercially available alpha-ionone. This highly efficient synthesis relies on the success of two consecutive highly regio- and stereoselective rearrangements. The current synthesis has not only established an efficient synthetic route to access the Ziegler intermediate but it has also paved a way to the structural optimization of forskolin.",10.1021/ol902133q,2009-10-30,0.6601294247579904
Organic Letters,Expedient Construction of the Ziegler Intermediate Useful for the Synthesis of Forskolin via Consecutive Rearrangements,"The Ziegler intermediate, useful for the total synthesis of forskolin, was synthesized in 10 reaction steps starting from commercially available α-ionone. This highly efficient synthesis relies on the success of two consecutive highly regio- and stereoselective rearrangements. The current synthesis has not only established an efficient synthetic route to access the Ziegler intermediate but it has also paved a way to the structural optimization of forskolin.",10.1021/ol102905a,2010-12-17,0.6601294247579904
Tetrahedron,Novel synthesis of benzo[b]carbazoles,,10.1016/j.tetlet.2014.07.070,2014-07-23,0.6601097431499512
Tetrahedron,A novel synthesis of benzocyclobutenones,,10.1016/s0040-4039(00)79113-1,1992-09-01,0.6601097431499512
Tetrahedron,Thiophenol additions to alkenylidenecyclopropanes. A novel synthesis of karahanaenone,,10.1016/s0040-4039(00)87118-x,1982-01-01,0.6601097431499512
Tetrahedron,Synthesis of novel nitroso-fulleropyrrolidines,,10.1016/s0040-4039(02)00944-9,2002-07-01,0.6601097431499512
Tetrahedron,A novel synthesis of 1-citronellol from 1-menthone,,10.1016/s0040-4039(01)82471-0,1974-01-01,0.6601097431499512
Tetrahedron,A novel synthesis of diarylacetylenes from N-arylmethylheteroarenes and N-arylmethyleneanilines,,10.1016/s0040-4039(00)79000-9,1992-10-01,0.6601097431499512
Tetrahedron,Synthesis of novel biaryl 2-benzimidazoles and 2-benzothiazoles,,10.1016/j.tetlet.2009.01.085,2009-01-21,0.6601097431499512
Tetrahedron,A novel synthesis of arcyriaflavin-A,,10.1016/0040-4039(95)00363-h,1995-04-01,0.6601097431499512
Tetrahedron,Synthesis of novel isoxazoline-fused cispentacin stereoisomers,,10.1016/j.tetlet.2009.03.119,2009-03-23,0.6601097431499512
Tetrahedron,"Synthesis of novel 6,7-dihydrothiazolo[3,2-b]-1,2,4-thiadiazine 1,1-dioxides",,10.1016/s0040-4039(02)00641-x,2002-05-01,0.6601097431499512
Tetrahedron,A novel synthesis of tetramesityldisilene,,10.1016/j.tetlet.2006.10.047,2006-11-01,0.6601097431499512
Tetrahedron,"A novel synthesis of 1,2-diphosphorylbenzenes",,10.1016/s0040-4039(01)90465-4,1981-01-01,0.6601097431499512
Synthesis,"A Novel Synthesis of 9,9′-Bifluorenylidene",,10.1055/s-1975-23793,1975-01-01,0.6601097431499512
Tetrahedron,A novel synthesis of 7-methoxycephalosporins and 6-methoxypenicillins,,10.1016/s0040-4039(00)78047-6,1976-04-01,0.6601097431499512
Tetrahedron,Synthesis of a decahydrohexapyrrin: A novel oligopyrrole of biosynthetic interest,,10.1016/0040-4039(95)02305-4,1996-02-01,0.6601097431499512
Tetrahedron,A novel synthesis of tetraphenyldiphosphine,,10.1016/s0040-4039(01)87507-9,1969-01-01,0.6601097431499512
Tetrahedron,Synthesis of novel 3′-isomeric dideoxynucleosides,,10.1016/s0040-4039(00)77150-4,1994-04-01,0.6601097431499512
Tetrahedron,Synthesis and conformational behaviour of novel cyclodextrin hetero-dimers,,10.1016/s0040-4039(00)78465-6,1994-11-01,0.6601097431499512
Synthesis,Novel Synthesis of α-Methylene-β-lactams,,10.1055/s-1980-29277,1980-01-01,0.6601097431499512
Tetrahedron,"Synthesis of 8-(3-methylbut-2-enoyl)-7-methoxycoumarin, a novel coumarin from",,10.1016/s0040-4039(01)83162-2,1977-01-01,0.6601097431499512
Tetrahedron,Synthesis of novel 3-formamido-3-acylamino-monobactams,,10.1016/s0040-4039(00)99206-2,1989-01-01,0.6601097431499512
Tetrahedron,"Novel tricyclic diamines 3. Synthesis of 1,4-diazaadamantane",,10.1016/j.tetlet.2018.01.031,2018-01-11,0.6601097431499512
Tetrahedron,"Novel tricyclic diamines 2. Synthesis of 1,7-diazaisoadamantane, 1,5-diazaisoadamantane and 1,6-diazahomobrendane",,10.1016/j.tetlet.2018.01.028,2018-01-11,0.6601097431499512
Tetrahedron,A novel synthesis of spirochromenes,,10.1016/s0040-4039(00)99676-x,1989-01-01,0.6601097431499512
Tetrahedron,Synthesis of Novel Hydroxyellipticines,,10.1016/0040-4039(94)88241-x,1994-09-01,0.6601097431499512
Tetrahedron,A novel synthesis of fluoroaromatics,,10.1016/s0040-4039(01)94562-9,1978-01-01,0.6601097431499512
Tetrahedron,Synthesis of novel nucleosides,,10.1016/s0040-4039(97)10531-7,1998-01-01,0.6601097431499512
Tetrahedron,A novel synthesis of S-glycosylphosphorodithioates,,10.1016/0040-4039(94)85341-x,1994-10-01,0.6601097431499512
Tetrahedron,A novel synthesis of (±) 2-epi-validamine,,10.1016/s0040-4039(98)01610-4,1998-10-01,0.6601097431499512
Tetrahedron,"Synthesis of novel 3′,6′-dideoxy-3′,6′-epithio and 2′,6′-dideoxy-2′,6′-epithio nucleosides",,10.1016/s0040-4039(98)00721-7,1998-06-01,0.6601097431499512
Tetrahedron,A novel synthesis of diaryl sulfides,,10.1016/s0040-4039(00)97931-0,1990-01-01,0.6601097431499512
Tetrahedron,Synthesis of novel oxa-isosteres of spermidine and spermine,,10.1016/s0040-4039(00)73252-7,1994-05-01,0.6601097431499512
Tetrahedron,"Synthesis of novel heterocycles : Oxazolo[4,5-b]pyridines and oxazolo[4,5-d]pyrimidines",,10.1016/s0040-4039(00)88750-x,1990-01-01,0.6601097431499512
Tetrahedron,"Synthesis of novel guanidine incorporated aminoglycosides, guanidinopyranmycins",,10.1016/s0040-4039(02)02248-7,2002-12-01,0.6601097431499512
Tetrahedron,Synthesis of novel 3′-methylene H-phosphonate thymidines,,10.1016/s0040-4039(00)01358-7,2000-10-01,0.6601097431499512
Tetrahedron,Novel synthesis of oxazines from 4-hydroxycoumarin and schiff bases.,,10.1016/s0040-4039(01)95007-5,1978-01-01,0.6601097431499512
Tetrahedron,"Thieno[3,4-c]thiophenes: novel synthesis of 1,3-dicarbomethoxy-4,6-dicyanothieno[3,4-c]thiophene",,10.1016/s0040-4039(00)01567-7,2000-11-01,0.6601097431499512
Synthesis,A Novel Synthesis of Dialkyl Arenephosphonates,,10.1055/s-1981-29335,1981-01-01,0.6601097431499512
Tetrahedron,A novel synthesis of β-ketosilanes via organoboranes,,10.1016/s0040-4039(00)01088-1,2000-08-01,0.6601097431499512
Tetrahedron,A novel hydrindane synthesis,,10.1016/s0040-4039(01)95729-6,1973-01-01,0.6601097431499512
Tetrahedron,A novel synthesis of Aporhoeadanes,,10.1016/s0040-4039(01)91055-x,1984-01-01,0.6601097431499512
Tetrahedron,Synthesis of novel tetrahydrobenzazepinones,,10.1016/0040-4039(92)88040-c,1992-01-01,0.6601097431499512
Tetrahedron,A novel synthesis of β-lactones,,10.1016/s0040-4039(01)87953-3,1969-01-01,0.6601097431499512
Tetrahedron,A novel synthesis of nor-C-statine.,,10.1016/s0040-4039(00)61770-7,1992-11-01,0.6601097431499512
Tetrahedron,"Novel synthesis of 2,4-diphenylquinolines",,10.1016/s0040-4039(00)78617-5,1980-01-01,0.6601097431499512
Tetrahedron,Novel synthesis of hexaaryl[3]radialenes via dibromo[3]dendralenes,,10.1016/s0040-4039(00)01211-9,2000-09-01,0.6601097431499512
Tetrahedron,"Novel synthesis of pyridazino[4,5-b][1,4]oxazin-3,8-diones☆",,10.1016/j.tetlet.2003.09.216,2003-11-14,0.6601097431499512
Tetrahedron,"Novel entry into oxepane–diquinane and oxepane–sterpurane hybrids: synthesis and photochemistry of 3-oxatricyclo[7.2.2.01,7]tridecenones",,10.1016/s0040-4039(02)02611-4,2003-01-01,0.6601097431499512
Tetrahedron,A novel synthesis of isorhynchophylline and rhynchophylline from secolaganin,,10.1016/s0040-4039(00)78077-4,1976-04-01,0.6601097431499512
Tetrahedron,"Novel synthesis of 2,3-diarylbuta-1,3-dienes from 1,4-dimethoxybutyne-2",,10.1016/s0040-4039(00)92765-5,1980-01-01,0.6601097431499512
Tetrahedron,A novel synthesis of juncusol,,10.1016/s0040-4039(00)79645-6,1991-03-01,0.6601097431499512
Angewandte Chemie International Edition,Novel Synthesis of Octaalkyl- or Octaisoalkylporphyrins,,10.1002/anie.198207180,1982-01-01,0.6601097431499512
Tetrahedron,"Novel tricyclic diamines 1. Synthesis of 1,4-diazaisotwistane and 1,4-diazahomoisotwistane as constrained 3-aminoquinuclidine isosteres",,10.1016/j.tetlet.2018.01.032,2018-01-11,0.6601097431499512
Tetrahedron,Novel synthesis of 3-oxazolines,,10.1016/s0040-4039(00)01723-8,2000-12-01,0.6601097431499512
Tetrahedron,A novel synthesis of thiophenes,,10.1016/s0040-4039(01)88885-7,1969-01-01,0.6601097431499512
Tetrahedron,Hydroboration of methoxyenynes. A novel synthesis of (E)-methoxyenones,,10.1016/s0040-4039(00)82071-7,1988-01-01,0.6601097431499512
Tetrahedron,A novel synthesis of pyrromethenones,,10.1016/s0040-4039(00)80618-8,1988-01-01,0.6601097431499512
Tetrahedron,A novel synthesis of cyclopentadecanone from cyclododecanone,,10.1016/s0040-4039(00)71561-9,1967-01-01,0.6601097431499512
Tetrahedron,A novel synthesis of acylsilanes,,10.1016/s0040-4039(00)93499-3,1991-09-01,0.6601097431499512
Tetrahedron,A novel synthesis of thiolactones: Selenothiolactonization,,10.1016/s0040-4039(00)84320-8,1986-01-01,0.6601097431499512
Tetrahedron,Novel synthesis of 2-thiazolines,,10.1016/s0040-4039(00)00419-6,2000-04-01,0.6601097431499512
Tetrahedron,"Novel synthesis of dibenzo[b,g]1,5-oxazocines",,10.1016/s0040-4039(99)01150-8,1999-08-01,0.6601097431499512
Tetrahedron,Synthesis of a novel β-turn mimetic and its incorporation in Leu-enkephalin,,10.1016/s0040-4039(99)01216-2,1999-08-01,0.6601097431499512
Tetrahedron,Synthesis of novel rigid-rod and tripodal azulene chromophores,,10.1016/j.tetlet.2005.05.034,2005-06-10,0.6601097431499512
Tetrahedron,Novel synthesis of ketocyanine dyes,,10.1016/s0040-4039(01)01210-2,2001-08-01,0.6601097431499512
Tetrahedron,"Quest for inosito-inositols: synthesis of novel, annulated and conformationally locked inositols",,10.1016/s0040-4039(03)00516-1,2003-03-26,0.6601097431499512
Tetrahedron,"Synthesis of a novel, conformationally restricted analog of tryptophan",,10.1016/s0040-4039(00)93413-0,1993-05-01,0.6601097431499512
Tetrahedron,A Novel Synthesis of the Fluorene Skeleton,,10.1016/s0040-4039(97)01534-7,1997-09-01,0.6601097431499512
Tetrahedron,Synthesis of a novel dicycloproparene,,10.1016/s0040-4039(97)00971-4,1997-06-01,0.6601097431499512
Tetrahedron,"A novel synthesis of 1,2-diazanaphthalenes",,10.1016/s0040-4039(97)10194-0,1997-11-01,0.6601097431499512
Tetrahedron,A novel synthesis of 4-halo-2H-chromenes,,10.1016/s0040-4039(00)74898-2,1991-02-01,0.6601097431499512
Tetrahedron,Synthesis of novel 5-oxaprotoberberines as bioisosteres of protoberberines,,10.1016/j.tetlet.2014.01.020,2014-01-13,0.6601097431499512
Tetrahedron,A novel synthesis of hasubanan skeleton,,10.1016/s0040-4039(00)77946-9,1976-03-01,0.6601097431499512
Tetrahedron,Novel synthesis of N-sulphinylamines from sulphur monoxide and azides,,10.1016/s0040-4039(01)92865-5,1977-01-01,0.6601097431499512
Tetrahedron,"Novel synthesis of α-arylnaphthalenes from diphenylacetaldehydes and 1,1-diphenylacetones",,10.1016/j.tetlet.2006.03.054,2006-03-31,0.6601097431499512
Tetrahedron,Synthesis of novel dendritic glycosides,,10.1016/0040-4039(95)01547-7,1995-10-01,0.6601097431499512
Tetrahedron,"Synthesis of novel 1,7-annulated 4,6-dimethoxyindoles",,10.1016/j.tetlet.2010.01.076,2010-01-29,0.6601097431499512
Tetrahedron,"Synthesis of a novel 1,4-bridged calix[8]arene “Host” cavity",,10.1016/s0040-4039(97)01202-1,1997-08-01,0.6601097431499512
Tetrahedron,Synthesis and complexation of a novel cyclophane,,10.1016/s0040-4039(00)94884-6,1985-01-01,0.6601097431499512
Tetrahedron,A novel synthesis of 4-cycloheptenones,,10.1016/s0040-4039(00)78974-x,1980-01-01,0.6601097431499512
Tetrahedron,Synthesis of novel macrobicyclic polyfunctional cryptands,,10.1016/s0040-4039(00)61883-x,1985-01-01,0.6601097431499512
Tetrahedron,"Synthesis of novel 8-thieno[2,3-]azepines by photolysis of 6-azido-2,3-dihydrobenzo[]thiophen",,10.1016/s0040-4039(00)94066-8,1983-01-01,0.6601097431499512
Tetrahedron,"Synthesis and cytotoxicity of novel 1-arylindolizines and 1-arylpyrrolo[2,1-a]isoquinolines",,10.1016/j.tetlet.2021.153552,2021-11-19,0.6601097431499512
Tetrahedron,Novel symmetrical triads of triphenylene-calix[4]arene-triphenylene: synthesis and mesomorphism,,10.1016/j.tetlet.2012.01.067,2012-01-31,0.6601097431499512
Tetrahedron,A novel synthesis of (±)-prostaglandin D2,,10.1016/s0040-4039(00)88113-7,1983-01-01,0.6601097431499512
Synthesis,A Novel Synthesis of Flavonols,,10.1055/s-1983-30533,1983-01-01,0.6601097431499512
Tetrahedron,Synthesis of novel photochromic fluorescing 2-indolylfulgimides,,10.1016/s0040-4039(99)01702-5,1999-11-01,0.6601097431499512
Tetrahedron,"A novel synthesis of 2-(2-quinoxalino)-3,5-diarylfurans",,10.1016/s0040-4039(98)01790-0,1998-10-01,0.6601097431499512
Tetrahedron,"Novel synthesis of sulfones from α,α-dibromomethyl aromatics",,10.1016/s0040-4039(02)02769-7,2003-02-01,0.6601097431499512
Tetrahedron,Synthesis of novel cationic lipids with oxyethylene spacers at the linkages between hydrocarbon chains and pseudoglyceryl backbone,,10.1016/s0040-4039(99)01683-4,1999-11-01,0.6601097431499512
Tetrahedron,a novel furan synthesis,,10.1016/s0040-4039(00)92808-9,1980-01-01,0.6601097431499512
Tetrahedron,A novel synthesis of 4-spirocyclopropyl β-lactams,,10.1016/s0040-4039(00)73822-6,1993-09-01,0.6601097431499512
Tetrahedron,"Synthesis of aaptamine, a novel marine alkaloid",,10.1016/s0040-4039(00)94864-0,1985-01-01,0.6601097431499512
Tetrahedron,Novel synthesis of benzyllithiums from benzylselenides,,10.1016/s0040-4039(00)98521-6,1985-01-01,0.6601097431499512
Tetrahedron,A novel synthesis of deoxy phospha sugar–sugar disaccharides,,10.1016/j.tetlet.2003.12.134,2004-01-30,0.6601097431499512
Tetrahedron,A novel synthesis of oxanosine and 1-thiaguanosine,,10.1016/s0040-4039(00)79951-5,1994-02-01,0.6601097431499512
Tetrahedron,"A novel synthesis of 1, 2-diaryl-2, 2-difluoroethanones",,10.1016/0040-4039(94)88398-x,1994-11-01,0.6601097431499512
Tetrahedron,A novel synthesis of 2′-deoxy-α-disaccharides,,10.1016/s0040-4039(01)85996-7,1979-01-01,0.6601097431499512
Tetrahedron,A novel synthesis of steroidal indoxyls and indoles,,10.1016/s0040-4039(00)70577-6,1962-01-01,0.6601097431499512
Tetrahedron,A novel synthesis of (+)-duocarmycin SA,,10.1016/s0040-4039(97)01716-4,1997-10-01,0.6601097431499512
Synthesis,Novel Synthesis of N-Sulfonylsulfoximines and N-Sulfonylsulfilimines,,10.1055/s-1971-21675,1971-01-01,0.6601097431499512
Tetrahedron,"A novel synthesis of 1-1,2-benzodiazepines",,10.1016/s0040-4039(00)91447-3,1975-01-01,0.6601097431499512
Tetrahedron,"Enolates of -hydroxyacetophenones: novel synthesis of 2,2-dialkyl-4-chromanones",,10.1016/s0040-4039(01)95497-8,1979-01-01,0.6601097431499512
Tetrahedron,First iodocyclization of β-allenic phosphonates: a novel synthesis of α-difluoromethylenephostones,,10.1016/j.tetlet.2006.06.096,2006-07-22,0.6601097431499512
Tetrahedron,A novel synthesis of selenophenes,,10.1016/s0040-4039(00)80307-x,1988-01-01,0.6601097431499512
Tetrahedron,Synthesis of a 5-deoxypyranoanthracycline : An entry into novel analogs of idarubicin,,10.1016/s0040-4039(00)73625-2,1993-05-01,0.6601097431499512
Tetrahedron,Alkylthiolation of alkenes a novel synthesis of episulphonium ions (thiiranium ions),,10.1016/s0040-4039(00)75191-4,1975-01-01,0.6601097431499512
Tetrahedron,A novel synthesis of noviose and its C-(4) epimer,,10.1016/s0040-4039(02)00500-2,2002-04-01,0.6601097431499512
Tetrahedron,A novel synthesis of quinone-imonium cation,,10.1016/s0040-4039(00)98641-6,1985-01-01,0.6601097431499512
Tetrahedron,Novel synthesis of physovenine and physostigmine analogs,,10.1016/j.tetlet.2016.06.005,2016-06-03,0.6601097431499512
Tetrahedron,A novel synthesis of (±)-descarboxyquadrone,,10.1016/s0040-4039(00)99937-4,1984-01-01,0.6601097431499512
Tetrahedron,Novel synthesis of a conformationally-constrained analog of DDATHF,,10.1016/s0040-4039(96)02397-0,1997-01-01,0.6601097431499512
Tetrahedron,Novel synthesis of Nectrisine and 4-epi-Nectrisine,,10.1016/s0040-4039(97)00636-9,1997-05-01,0.6601097431499512
Tetrahedron,Synthesis of novel tricyclononanes,,10.1016/s0040-4039(97)01165-9,1997-07-01,0.6601097431499512
Tetrahedron,"A novel synthesis of 1,2,4-triazines",,10.1016/s0040-4039(01)96849-2,1971-01-01,0.6601097431499512
Tetrahedron,A novel synthesis of cyclopentenones and cyclohexenones via cycliacylation of lithioalkenylcarboxamides,,10.1016/s0040-4039(00)84098-8,1986-01-01,0.6601097431499512
Tetrahedron,A novel synthesis of (-)-carpetimycin A,,10.1016/s0040-4039(00)98966-4,1985-01-01,0.6601097431499512
Tetrahedron,A novel synthesis of benzo[b]oxepines,,10.1016/s0040-4039(01)85208-4,1972-01-01,0.6601097431499512
Tetrahedron,"A novel synthesis of 2,5-diaryl-3-(phenylmethyl)thiophenes",,10.1016/s0040-4039(00)60770-0,1993-03-01,0.6601097431499512
Tetrahedron,Synthesis of 9-dihydrotaxol: A novel bioactive taxane,,10.1016/s0040-4039(00)60342-8,1993-03-01,0.6601097431499512
Tetrahedron,"Synthesis of 4-Oxa-2-azapodophyllotoxin, a novel analog of the antitumor lignan podophyllotoxin",,10.1016/s0040-4039(00)78553-4,1994-12-01,0.6601097431499512
Tetrahedron,Synthesis of novel unsymmetrical monoaminated phthalocyanines,,10.1016/0040-4039(95)01781-c,1995-11-01,0.6601097431499512
Synthesis,The Synthesis of Novel Oxa-Azamacrocycles,,10.1055/s-1999-6066,1999-06-01,0.6601097431499512
Tetrahedron,A novel synthesis of 9-hydroxyaporphine,,10.1016/s0040-4039(01)91089-5,1984-01-01,0.6601097431499512
Tetrahedron,Novel synthesis of a Phe-Gly E-alkene dipeptide isostere,,10.1016/0040-4039(96)01108-2,1996-07-01,0.6601097431499512
Tetrahedron,Novel fragmentation of longibornane system: synthons for α-longipinene synthesis,,10.1016/s0040-4039(01)84419-1,1972-01-01,0.6601097431499512
Tetrahedron,"Cyclization of α,α-Difluoromethyl Radicals: A New Route to the Preparation of Difluorocyclopentane Derivatives",,10.1016/s0040-4039(00)79414-7,1991-10-01,0.6601006233335757
Tetrahedron,An efficient synthesis of isocarbacyclin starting from furfural,,10.1016/s0040-4039(01)91126-8,1984-01-01,0.6600904873201858
Journal of Organic Chemistry,An Improved Total Synthesis of (+)-Macroline and Alstonerine as Well as the Formal Total Synthesis of (−)-Talcarpine and (−)-Anhydromacrosalhine−methine,An intramolecular Pd-catalyzed alpha-vinylation process is described. This cyclization has been employed for the enantiospecific total synthesis of gram quantities of both (+)-macroline 3 and the macroline equivalent 4. This sequence is compared to the enolate-driven cross-coupling process. The intermediate 4 was also converted into (-)-alstonerine 1 via modification of an intramolecular Tsuji-Wacker oxidation. This sequence resulted in an improved total synthesis of (-)-talcarpine 5 and (-)-anhydromacrosalhine-methine 6 as well.,10.1021/jo061652u,2006-10-07,0.6600729528638982
Journal of the American Chemical Society,"Synthesis of Streptolydigin, a Potent Bacterial RNA Polymerase Inhibitor","Streptolydigin is a highly potent, broad-spectrum antibiotic produced by Streptomyces lydicus, which inhibits bacterial RNA polymerase. We describe the first synthesis of streptolydigin, which was assembled in a highly convergent and fully stereocontrolled fashion with a longest linear sequence of 24 steps starting from commercially available precursors. The assembly process entailed preparation of fully elaborated streptolic and ydiginic subunits of the natural product, followed by a highly efficient union in a three-step one-pot procedure, which included Dieckmann cyclization with a concomitant imide opening, Horner-Wadsworth-Emmons olefination, and desilylation.",10.1021/ja107190w,2010-09-29,0.6600670700742539
Journal of Organic Chemistry,Total Synthesis of (±)-Aspidospermidine,"(+/-)-Aspidospermidine (1) has been synthesized from readily available methyl 3-ethyl-2-oxocylo-pentanecarboxylate (17) in 5.9% yield over 13 steps. The key step of the synthesis is an intramolecular cascade reaction that simultaneously forms the B, C, and D rings of 1. A high-yielding method of closing the remaining E ring is also described.",10.1021/jo991599s,2000-04-13,0.6600445893104383
Organic Process Research & Development,Development of a Practical and Scalable Process for Lifitegrast,"A practical and scalable manufacturing process for the anti-inflammatory drug lifitegrast, approved by the FDA in 2016 for the treatment of dry eye disease, was developed from commercially available starting materials. Key features of the approach are protecting-group-free synthesis that led to inhibition of racemization of lifitegrast during amide coupling and a process to remove oligomerization impurities and the undesired optical isomer of lifitegrast formed due to the presence of the corresponding optical isomer from the chiral starting material. Lifitegrast manufactured from this route complied with the quality guidelines as per the International Council of Harmonization (ICH).",10.1021/acs.oprd.3c00228,2023-09-25,0.6600275564950718
Tetrahedron,A new route for the construction of the AB-ring core of Taxol,,10.1016/s0040-4039(02)02868-x,2003-02-01,0.6600180289117764
Tetrahedron,Reactions of β-fluorovinamidinium salt with bifunctional hetero nucleophiles. A new synthetic route to fluorinated heterocycles,,10.1016/0040-4039(95)00076-o,1995-02-01,0.6600085176651508
Journal of Organic Chemistry,Total Synthesis of the Antimitotic Marine Natural Product (+)-Curacin A,"The structurally novel antimitotic agent curacin A was prepared in 15 steps and in 2.6% yield for the longest linear sequence. Key steps in our synthesis are the use of a hydrozirconation-transmetalation protocol for the preparation of divinyl alcohol 8, the stereoselective formation of the acyclic triene segment 11 via enol triflate chemistry, and a second hydrozirconation of the conjugated triene followed by an isocyanide insertion. For the preparation of the heterocyclic moiety of curacin A, the oxazoline --> thiazoline conversion offered an efficient access to the sensitive marine natural product.",10.1021/jo960845m,1996-01-01,0.6600034314844986
Organic Process Research & Development,Process Development of a Novel Route to Rilpivirine Hydrochloride,"An efficient synthetic route to access rilpivirine hydrochloride was designed and demonstrated on a multikilogram scale. The synthetic route uses two subsequent aromatic nucleophilic substitutions, conducted under carefully optimized conditions to access the target in a 39% overall yield over four steps from ( E )-3-(4-amino-3,5-dimethylphenyl)acrylonitrile hydrochloride 5 . The procedures developed were demonstrated on multikilogram scale in our pilot plant, and the product was obtained with a purity of 99.6% by HPLC with no single impurity above 0.10%. The challenges associated with polymorph control and impurity control in an active pharmaceutical ingredient (API) are also discussed. Overall, our process toward Rilpivirine is shorter than most processes described and displays smooth reaction conditions. This work showcases the use of a Boc protecting group as a handle to achieve a more selective nucleophilic aromatic substitution process. It also illustrates the importance of solvent choice in process development to make the chemistry applicable on a large scale under safe conditions.",10.1021/acs.oprd.3c00326,2024-02-08,0.6600006515684553
Organic Letters,Enantioselective Synthesis of Slagenins A−C,[formula: see text] An enantioselective synthesis of slagenins A-C (1a-c) is described in which their absolute stereochemistries were established. The key step in the synthesis involved the efficient condensation of 2-methoxy-dihydro-furan-3-one 9 and urea to construct the slagenin bicycle core.,10.1021/ol0268034,2002-10-01,0.6599720525426188
Organic Process Research & Development,Highly Efficient Multigram Synthesis of Dibenzoazacyclooctyne (DBCO) without Chromatography,"The synthesis of 4-[11,12-didehydrodibenzo[ b, f ]azocin-5(6 H )-yl]-4-oxobutanoic acid, also known as dibenzoazacyclooctyne (DBCO) or aza-dibenzocyclooctyne (ADIBO), was optimized for large-scale preparations of at least 10 g with an overall yield of 42%.",10.1021/acs.oprd.9b00406,2019-11-12,0.6599669756274169
Organic Process Research & Development,Development of a Scalable Negishi Cross-Coupling Process for the Preparation of 2-Chloro-5-(1-(tetrahydro-2<i>H</i>-pyran-2-yl)-1<i>H</i>-pyrazol-5-yl)aniline,"A scalable synthesis of 2-chloro-5-(1-(tetrahydro-2 H -pyran-2-yl)-1 H -pyrazol-5-yl)aniline ( 1 ), a key intermediate in the synthesis of an immuno-oncology asset, is described. A Negishi cross-coupling between in situ generated heteroaryl zinc reagent 4 and 5-bromo-2-chloroaniline ( 3 ) catalyzed by Pd(Xantphos)Cl 2 enabled the construction of the key aryl–heteroaryl bond. A scalable first-generation process was developed that delivered 1 in multikilogram quantities. Building upon knowledge from the initial process, a more efficient workup and isolation procedure was developed that controlled levels of residual Pd and Zn to consistent levels that were acceptable for downstream processing. The high-yielding optimized process offers streamlined metals remediation, a 30% reduction in the number of unit operations, and a 34% reduction in process mass intensity (PMI) compared to the initial process.",10.1021/acs.oprd.0c00414,2020-12-23,0.6599361423238317
Tetrahedron,"A new route to 1,3-dithioles from mesoionic 2-piperidino-5-aryl-1,3-dithiolium-4-thiolates. Synthesis of 2(1,3-dithiolan-2-ylidene)-1,3-dithioles and tetrathiafulvalenes using these new dithioles.",,10.1016/s0040-4039(00)73976-1,1993-08-01,0.6599233161690006
Organic Process Research & Development,The Development of a Manufacturable Synthesis of LY213829,"The development of a manufacturable synthesis of LY213829 (4-thiazolidinone-5-[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl] methyl) is described. Rather than reduction to eliminate the thiocarbonyl from the rhodanine moiety, the new route utilizes a novel concurrent ring opening with ammonia and re-cyclization with formaldehyde. This change obviates a potentially problematic zinc solid waste stream.",10.1021/op990197j,2000-05-06,0.6599082262709823
Organic Letters,Asymmetric Total Synthesis of (−)-Lemnalemnane C,"The first asymmetric total synthesis of tricyclic sesquiterpenoid lemnalemnane C, which exhibits strong in vivo angiogenesis-promoting activity, has been accomplished. The key synthesis steps include the construction of two five-membered rings via pinacol coupling and the stereoselective introduction of an allyl group with double-bond isomerization.",10.1021/acs.orglett.5c00649,2025-07-04,0.6598556097676939
Journal of Organic Chemistry,The First Total Synthesis of (+)-Ratjadone,"The first total synthesis of ratjadone was achieved using a highly convergent approach joining three subunits together with a Wittig olefination and a selective Heck reaction as the pivotal steps. Besides establishing a robust and reliable route for the synthesis of this orphan ligand, the configuration of unknown stereocenters could also be determined. This synthesis not only provides an additional access to a biologically important compound but also enables the synthesis of structural analogues for biological target identification.",10.1021/jo005768g,2001-02-07,0.6598469465114153
Organic Letters,Total Synthesis of (+)-Strongylophorines 2 and 9,"The first enantioselective total syntheses of highly complex hexacyclic meroterpenoids STR-2 and -9 (strongylophorine (STR)) are reported. Key elements of the synthetic route include the use of Robinson-type annulation reaction to construct the tricyclic terpenoid building block and a highly efficient PIDA-mediated 1,3-diaxial sp 3 C–H activation to incorporate the requisite δ-lactone moiety. This route also enables the determination of absolute configuration of the synthesized natural products.",10.1021/acs.orglett.9b01254,2019-05-07,0.6598443508356866
Organic Letters,Total Synthesis of (−)-Actinophyllic Acid Enabled by a Key Dual Ir/Amine-Catalyzed Allylation,"A synthetic strategy for the catalytic asymmetric total synthesis of (-)-actinophyllic acid is described. This highly efficient and enantioselective approach allows the rapid installation of the four contiguous chiral centers (C16, C15, C20, and C19) by way of a dual Ir/amine catalytic allylation of 2-indolyl vinyl carbinol 6 and an aldol reaction of resultant chiral aldehyde 4a with 2-pyrrolidinone 5. The key indol-3-ylmethanamine moiety and 1-azabicyclo[4.2.1]nonane ring system were readily generated through a selective Mannich-like cyclization and an intramolecular N-alkylation, respectively.",10.1021/acs.orglett.8b01861,2018-07-13,0.6598414073660706
Organic Letters,"Enantioselective Total Synthesis of (+)-Iso-A82775C, a Proposed Biosynthetic Precursor of Chloropupukeananin","(+)-Iso-A82775C is a proposed biosynthetic precursor of the chloropupukeananin family and an important intermediate for related natural products. The first enantioselective total synthesis of (+)-iso-A82775C (18 steps, 2.2% overall yield) toward the eventual biomimetic total synthesis of chloropupukeananin is described. The key steps are (1) the enantioselective Diels–Alder reaction of 4-bromo-3-hydroxy-2-pyrone with methyl 2-chloroacrylate using cinchonine as an organocatalyst and (2) the anti -selective Cu-mediated S N 2′ reaction to afford the axially chiral vinylallene moiety.",10.1021/acs.orglett.7b00085,2017-01-27,0.6598281915378593
Synthesis,"Concise Synthesis of the ABC-Ring System of the Azafluoranthene, Tropoisoquinoline and Proaporphine Alkaloids: An Olefin Hydroacylation/Pomeranz–Fritsch Cyclization Approach","A straightforward approach toward a decorated cyclopenta[ij]isoquinoline embodying the ABC-ring system characteristic of the azafluoranthene (triclisine), tropoisoquinoline (pareitropone) and proaporphine (prodensiflorin B) alkaloids, is reported. The synthetic ­sequence entailed a novel 40% KF/Al2O3-mediated hydroacylation of a 2-allyl-benzaldehyde derivative, obtained in two steps from isovanillin, through O-allylation and Claisen rearrangement to assemble the AC-ring system. This was followed by an O-methylation and a reductive ­amination of the resulting indanone with aminoacetal. A modified Pomeranz–Fritsch cyclization was next implemented to install ring B, through sulfonamidation, followed by acid-promoted cyclization and ­final desulfonylation in situ.",10.1055/s-0037-1611711,2019-01-29,0.6598055465733457
Organic Letters,"Short, Divergent, and Enantioselective Total Synthesis of Bioactive <i>ent</i>-Pimaranes","High Resolution Image Download MS PowerPoint Slide We present the first total synthesis of eight ent -pimaranes via a short and enantioselective route (11–16 steps). Key features of the divergent synthesis are a Sharpless asymmetric dihydroxylation, a Brønsted acid catalyzed cationic bicyclization, and a mild Rh-catalyzed arene hydrogenation for rapid access to a late synthetic branching point. From there on, selective functional group manipulations enable the synthesis of ent -pimaranes bearing different modifications in the A- and C-rings.",10.1021/acs.orglett.2c02843,2022-09-28,0.6597922118534914
Angewandte Chemie International Edition,Synthesis of the Kedarcidin Core Structure by a Transannular Cyclization Pathway,"The chromoprotein enediyne antibiotic kedarcidin has a structurally complex and highly reactive chromophore component. An enantioselective synthesis of compound 1, which contains the full functionality of the chromophore core, is described. The key step in the synthetic route involves low-temperature halogen–lithium exchange initiated transannular cyclization of the macrocyclic vinyl bromide 2. TBS=tert-butyldimethylsilyl.",10.1002/1521-3773(20000804)39:15<2732::aid-anie2732>3.0.co;2-9,2000-08-04,0.6597635007147197
Organic Process Research & Development,Asymmetric Synthesis of the Antiarrhythmia Agent <i>d</i>-Sotalol,A chiral synthesis of d -Sotalol was developed starting from commercially available 4‘-(chloroacetyl)methanesulfonanilide ( 2 ).,10.1021/op960043t,1997-03-01,0.6597515309907557
Angewandte Chemie International Edition,An Efficient Total Synthesis of Optically Active Tetrodotoxin,"The toxic principle of puffer-fish poison, (−)-tetrodotoxin (1), has been recognized as a formidable synthetic target since its structure elucidation in 1964. An efficient total synthesis of 1 via the intermediate 2, which was used previously for the synthesis of 11-deoxytetrodotoxin, is described.",10.1002/anie.200460293,2004-09-07,0.659729352564716
Tetrahedron,"A practical synthetic route to enantiopure 3-aryloxy-1,2-propanediols from chiral glycidol",,10.1016/0040-4039(95)00282-h,1995-04-01,0.6597031258061941
Organic Letters,Total Synthesis of Phoslactomycin A,"A convergent total synthesis of the PP2A-inhibitor phoslactomycin A was achieved using a CuTC-mediated coupling of an alkenyl iodide C1-C13 fragment with an C14-C21 alkenyl stannane in the presence of a protected phosphate. Key features for the assembly of the C1-C13 fragment were an asymmetric dihydroxylation, an Evans-Aldol reaction, and a well-balanced protective group strategy. An asymmetric 1,4-addition to cyclohexenone was the key step in the preparation of the C14-C21 fragment.",10.1021/ol900757k,2009-06-01,0.6596740714731184
Angewandte Chemie International Edition,Scalable Synthesis of the Potent HIV Inhibitor BMS‐986001 by Non‐Enzymatic Dynamic Kinetic Asymmetric Transformation (DYKAT),"Described herein is the synthesis of BMS-986001 by employing two novel organocatalytic transformations: 1) a highly selective pyranose to furanose ring tautomerization to access an advanced intermediate, and 2) an unprecedented small-molecule-mediated dynamic kinetic resolution to access a variety of enantiopure pyranones, one of which served as a versatile building block for the multigram, stereoselective, and chromatography-free synthesis of BMS-986001. The synthesis required five chemical transformations and resulted in a 44% overall yield.",10.1002/anie.201502290,2015-04-29,0.6596674522791884
Angewandte Chemie International Edition,Enantioselective Total Synthesis of the Diterpene (+)‐Cubitene,"From termite soldier's secretions: The enantioselective total synthesis of the diterpene (+)-cubitene is described. The route is characterized by the cyclization of a carvone-derived C20 allylphosphate with SmI2, followed by fragmentation to the twelve-membered ring. As a result, perfect stereocontrol of the isopropenyl-substituted positions is achieved.",10.1002/anie.201205143,2012-09-25,0.659653753150694
Organic Letters,"(+)-Phorboxazole A Synthetic Studies. A Highly Convergent, Second Generation Total Synthesis of (+)-Phorboxazole A","[structure: see text] A second generation total synthesis of the potent antitumor agent (+)-phorboxazole A (1) has been achieved. The cornerstone of this approach comprises a more convergent strategy, involving late-stage Stille union of a fully elaborated C(1-28) macrocycle with a C(29-46) side chain. The second generation synthesis entails the longest linear sequence of 24 steps, with an overall yield of 4.2%.",10.1021/ol051584i,2005-09-01,0.6596480878401321
Tetrahedron,Toward a total synthesis of amphidinolide N: convergent synthesis of the C1–C13 segment,,10.1016/j.tetlet.2016.06.107,2016-06-23,0.6596231896939649
Organic Process Research & Development,Development of a Kilogram-Scale Synthesis of a Key Ulevostinag Subunit Part I: Accessing a Keto-Nucleoside Intermediate from Guanosine,"A kilogram-scale synthesis of a key fragment of Ulevostinag (MK-1454), a cyclic dinucleotide agonist of the stimulator of interferon genes (STING), is described. Ulevostinag comprises two non-natural nucleoside derivatives linked together via two P -chiral phosphorothioate groups. The strategy utilized to prepare one of these nucleosides, namely, 3′-deoxy-3′-α-fluoro-guanosine (3′-FG), hinges on a diastereoselective α-fluorination of a key keto-nucleoside derivative, followed by substrate-directed reduction of the ketone. Herein, we describe the development of a robust and scalable synthesis of this intermediate, a 3′-deoxy-2′-keto-guanosine derivative, from guanosine. Salient features of the approach include activation of the 2′ and 3′-alcohol groups of guanosine as a bis-tosylate, which enables regioselective E2 elimination to simultaneously deoxygenate the 3′-position and generate the 2′-ketone.",10.1021/acs.oprd.2c00397,2023-03-07,0.659611448389902
Organic Process Research & Development,Synthesis of Lenacapavir Sodium: Active Pharmaceutical Ingredient Process Development and Scale-up,"Lenacapavir sodium (GS-6207-02) is a first-in-class HIV capsid inhibitor. Process development of the four-step final assembly of lenacapavir sodium from four synthetic intermediates is described here. A bis-bromopyridine core is sequentially subjected to an alkynylation, an amide coupling with a chiral pyrazole carboxylic acid, and a Suzuki cross-coupling with an indazole boronic ester. The final step is a telescoped bis-methanesulfonylation and hydrolysis to yield the API. This report highlights experimental work on the final assembly sequence to establish robust processing conditions, minimize process mass intensity, control impurity formation, understand impurity purge, and enable large-scale manufacturing of lenacapavir sodium.",10.1021/acs.oprd.4c00242,2024-07-31,0.6595937055003508
Journal of Organic Chemistry,Leucascandrolide A:  Synthesis and Related Studies,"The total synthesis of the biologically active marine natural product leucascandrolide A is reported. A convergent strategy is employed, allowing for the rapid assembly of the macrolide moiety. Key steps of our approach include the diastereoselective addition of a zinc alkynilide to (R)-isopropylidene glyceraldehyde, the enantioselective copper(I) fluoride catalyzed aldol addition of a TMS-dienolate to crotonaldehyde, and the formation of a 2,6-trans-substituted tetrahydropyran by selenium-mediated intramolecular cyclization. Moreover, dramatic solvent effects observed in the macrolactonization reaction suggest that hydrogen-bonding effects play a critical role. An improved route to a key intermediate of our synthesis is documented.",10.1021/jo034964v,2003-10-31,0.6595906380730756
Journal of the American Chemical Society,A Formal Synthesis of (−)-Mycalamide A,"Novel strategies are developed for an efficient formal synthesis of (-)-mycalamide A. The left-hand side (-)-7-benzoylpederic acid is synthesized from (2S,3S)-2,3-epoxybutane. The key features include a highly regioselective Ru-catalyzed alkene-alkyne coupling reaction and a novel way to control the challenging C(7) stereocenter. The right-hand side was synthesized from (R)-pantolactone. The complex trioxodecalin core is constructed with two Pd(0)-catalyzed O-pi-allyl cyclizations. The first one is chemoselective, while the second one is highly diastereoselective. Three additional steps would be required to complete a total synthesis of (-)-mycalamide A.",10.1021/ja038787r,2003-12-11,0.6595884845318881
Organic Letters,"A Novel, Selective, and Efficient Route to Carotenoids and Related Natural Products via Zr-Catalyzed Carboalumination and Pd- and Zn-Catalyzed Cross Coupling","[structure: see text]. A highly efficient and stereoselective protocol for the syntheses of symmetrical and unsymmetrical carotenoids involving Zr-catalyzed carboalumination of conjugated oligoenynes and Pd- and Zn-catalyzed alkenyl-alkenyl coupling has been developed and applied to the syntheses of beta- and gamma-carotene and vitamin A. gamma-Carotene of > or =99% isomeric purity was prepared in three linear steps (five steps overall) from beta-ionone, enyne 8, (E)-ICH=CHBr, and (E)-Me3SiC triple bond CCH=CHBr in 32% overall yield.",10.1021/ol000384y,2001-02-06,0.6595647157328987
Journal of the American Chemical Society,"Toluene Dioxygenase-Mediated <i>cis</i>-Dihydroxylation of Aromatics in Enantioselective Synthesis. Asymmetric Total Syntheses of Pancratistatin and 7-Deoxypancratistatin, Promising Antitumor Agents<sup>1</sup>","Whole-cell biooxidation of bromobenzene with Pseudomonas putida 39D or the recombinant Escherichia coli JM109 (pDTG601) yields (1 S,2 S )-3-bromocyclohexa-3,5-diene-1,2-diol ( 9a ), which is protected as the acetonide and converted to vinylaziridines 7, 15a, 63, and 64 . Our route to (+)-pancratistatin features the coupling of a higher order cyanocuprate (derived by ortho -metalation from N, N -dimethyl-2-[( tert -butyldimethylsilyl)oxy]-3,4-(methylenedioxy)benzamide) with aziridine 7 to generate 28, which contains the carbon framework of the title alkaloid. Functional group manipulations resulted in the preparation of epoxydiol 50, which was transformed in a unique fashion and under mild conditions (H 2 O/PhCO 2 Na) to (+)-pancratistatin, thus completing a concise synthesis of (+)-pancratistatin in 14 steps from bromobenzene (2% overall yield). To improve this first generation attempt, a new route was devised utilizing carbomethoxyaziridine 64 and its coupling to the cuprate of 3,4-(methylenedioxy)bromobenzene. The adduct was converted to (+)-7-deoxypancratistatin in a total of 11 steps from bromobenzene (3% overall yield), and the basis for further improvement toward a practical synthesis of pancratistatin-type alkaloids was formulated.",10.1021/ja960596j,1996-01-01,0.659533480683841
Journal of Organic Chemistry,A direct synthesis of .beta.-hydroxybutyrolactones. Total synthesis of dendrolasin and formal total synthesis of aplysistatin,The 6-hydroxybutyrolactone unit has been employed as a building block for the synthesis of several furans and sesquiterpenes. Negishi and co-workers' developed a clever route to dendrolasin (1).,10.1021/jo00174a038,1983-12-01,0.659528129414059
Organic Process Research & Development,"Patent Review of Manufacturing Routes to Recently Approved Oncology Drugs: Ibrutinib, Cobimetinib, and Alectinib","This article reviews the patent literature on synthetic routes and API forms of recently approved orally active tyrosine kinase inhibitors for the treatment of cancer, including Imbruvica (ibrutinib), Cotellic (cobimetinib), and Alecensa (alectinib). Although the patents for ibruitinib published in the FDA Orange Book do not start expiring until late 2026, 13 patents have been filed on alternate routes and 11 on final forms of the API by the innovators and generic firms. Regarding cobimetinib, a nonscalable route used during discovery efforts required an alternate route for development; an efficient route was developed and used throughout clinical development and commercialization. A productive second-generation eight-step linear route to alectinib, with an average yield of 89% per step, was designed and developed to support development and commercialization.",10.1021/acs.oprd.6b00304,2016-10-10,0.6595245369177996
Synthesis,"Total Synthesis of Anticancer Pacharin, Bauhiniastatin 4, and Bauhinoxepins C and D","Abstract Reported herein is the total synthesis of anticancer pacharin, bauhiniastatin 4, and bauhinoxepins C and D. The synthetic strategy features a cascade reaction involving intermolecular nucleophilic aromatic substitution followed by intramolecular Knoevenagel condensation to form a dibenzo[b,f]oxepine scaffold of these compounds. Pacharin and bauhiniastatin 4 were synthesized in eight steps from 2-methylresorcinol with overall yields of 5.4% and 8.3%, respectively. Similarly, bauhinoxepins C and D were synthesized in seven steps with overall yields of 3.5% and 2.6%, respectively. This methodology offers an efficient route for accessing these natural products with implications for medicinal and synthetic chemistry.",10.1055/a-2550-7239,2025-03-04,0.6595222603456101
Organic Process Research & Development,"Synthesis of the Potent Antiglaucoma Agent, Travoprost","A commercial synthesis of the antiglaucoma agent, travoprost 2, is described. A total of 22 synthetic steps are required to provide the single enantiomer prostanoid, with the longest linear sequence being 16 steps from 3-hydroxybenzotrifluoride. The route is based upon a cuprate-mediated coupling of the single enantiomer vinyl iodide 13 and the tricyclic ketone 5, of high stereochemical purity, to yield the single isomer bicyclic ketone 15 . A Baeyer−Villiger oxidation provides the lactone 16 as a crystalline solid, thus limiting the need for chromatographic purification. DIBAL-H reduction, Wittig reaction, esterification, and silyl group deprotection complete the synthesis of travoprost.",10.1021/op010097p,2002-02-07,0.6594938992861694
Journal of Organic Chemistry,An Enantioselective Synthesis of the Key Intermediate for Triazole Antifungal Agents; Application to the Catalytic Asymmetric Synthesis of Efinaconazole (Jublia),"A new synthetic route, the shortest reported to date, to access a key intermediate for the synthesis of various triazole antifungal agents was developed. The elusive tetrasubstituted stereogenic center that is essential in advanced triazole antifungal agents was constructed via the catalytic asymmetric cyanosilylation of a ketone. The subsequent transformations were performed in two one-pot operations, enhancing the overall synthetic efficiency toward the intermediate. This streamlined synthetic approach was successfully applied to efficient enantioselective syntheses of efinaconazole (Jublia) and ravuconazole.",10.1021/jo500369y,2014-03-17,0.6594871013541228
Tetrahedron,"Stereoselective synthesis of C-9 to C-14 segment, a key intermediate for the total synthesis of trienomycin and micotrienins.",,10.1016/s0040-4039(00)60494-x,1993-04-01,0.6594793671776823
Journal of the American Chemical Society,The Total Synthesis of (−)-Lemonomycin,"The first total synthesis of the novel glycosylated tetrahydroisoquinoline antitumor antibiotic (-)-lemonomycin has been accomplished (15 steps from 9). The highly convergent synthesis relies on a key asymmetric dipolar cycloaddition to set the stereochemistry of the aglycone core, a Suzuki fragment coupling to connect the diazabicycle to the aryl subunit, and a stereoselective Pictet-Spengler reaction that incorporates the aminoglycoside subunit directly into the core structure without the need for late-stage glycosylation or protecting group manipulations. The novel aminoglycoside was prepared using a highly diastereoselective Felkin-controlled acetate aldol addition reaction to a threonine-derived ketone.",10.1021/ja039223q,2003-11-14,0.6594440595485597
Tetrahedron,"Indoloquinones, part 5. Palladium-catalyzed total synthesis of the potent lipid peroxidation inhibitor carbazoquinocin C",,10.1016/s0040-4039(98)01888-7,1998-11-01,0.6594418216382535
Angewandte Chemie International Edition,"A Convergent Strategy for the Pamamycin Macrodiolides: Total Synthesis of Pamamycin‐607, Pamamycin‐593, and Pamamycin‐621D Precursors","A convergent total synthesis of pamamycin-607 (1), isolated from Streptomyces alboniger, was achieved by an E–Z isomerization of a tetrahydrofuran alkylidene and a regio- and diastereoselective solvent-dependent cyclo-C6H11BCl/Et3N-mediated aldol reaction as the key steps. The second key step was extended to other ketones, opening the route to new pamamycin macrodiolides, for example, pamamycin-593 and pamamycin-621D.",10.1002/anie.200701749,2007-08-07,0.6594388314369087
Organic Process Research & Development,Synthesis of an Oxathiolane Drug Substance Intermediate Guided by Constraint-Driven Innovation,"A new route was developed for construction of the oxathiolane intermediate used in the synthesis of lamivudine (3TC) and emtricitabine (FTC). We developed the presented route by constraining ourselves to low-cost, widely available starting materials-we refer to this as supply-centered synthesis. Sulfenyl chloride chemistry was used to construct the framework for the oxathiolane from acyclic precursors. This bond construction choice enabled the use of chloroacetic acid, vinyl acetate, sodium thiosulfate, and water to produce the oxathiolane.",10.1021/acs.oprd.0c00145,2020-05-13,0.6594297637984952
Angewandte Chemie International Edition,Total Syntheses of Polyhydroxylated Steroids by an Unsaturation‐Functionalization Strategy,"Abstract Highly oxygenated cardiotonic steroids, such as ouabain, possess a wide spectrum of biological functions and remain significant synthetic challenges. Herein, we have applied an unsaturation‐functionalization strategy and developed a synthetic method in addressing the C19‐hydroxylation issue for efficient synthesis of polyhydroxylated steroids. An effective asymmetric dearomative cyclization allowed the construction of the C19‐hydroxy unsaturated steroidal skeleton in only four steps from the Hajos‐Parrish ketone ketal 7 . The synthetic sequence featured C3−OH‐directed hydrogenation/epoxidation, m ‐CPBA‐triggered epoxidation/S N 2′ nucleophilic substitution, Birch reduction of an enone, and regioselective LiAlH 4 reduction to furnish the polyhydroxy functionalities on the steroid skeleton with high stereochemical control and efficiency. This approach ultimately enabled the total synthesis of 19‐hydroxysarmentogenin and ouabagenin in 18 and 19 steps, respectively, overall. The synthesis of these polyhydroxylated steroids offers synthetic versatility and practicality in the search for new therapeutic agents.",10.1002/anie.202303639,2023-04-21,0.6594199041630396
Journal of Organic Chemistry,Total Synthesis of (−)-Callystatin A,A total synthesis of the cytotoxic polyketide marine natural product callystatin A is described. The route features chiral allenylmetal additions to construct the polypropionate C15-22 segment and an sp(2)-sp(3) Suzuki coupling to join the C1-C11 and C12-C22 subunits.,10.1021/jo016025d,2001-12-18,0.6594105526764851
Angewandte Chemie International Edition,A New Enantioselective Approach to Total Synthesis of the Securinega Alkaloids: Application to (−)-Norsecurinine and Phyllanthine,An inexpensive proline derivative and chiral control feature in the total synthesis of securinega alkaloids (-)-norsecurinine (1) and phyllanthine (2). Key steps in the synthesis of 1 include an intramolecular ketonitrile coupling and application of a radical-based generation of N-acylimines. The total synthesis of 2 utilizes a stereoselective imino Diels - Alder construction of the methoxypiperidine ring.,10.1002/(sici)1521-3773(20000103)39:1<237::aid-anie237>3.0.co;2-b,2000-01-03,0.6594099166239394
Organic Process Research & Development,The Synthesis of Two Potent β-3 Adrenergic Receptor Agonists,This contribution describes the initial preparation of two potent β-3 receptor agonists 1 and 2 . Subsequent scale up of these two compounds was required for further evaluation and proceeded via a common key amine intermediate 24 . Synthesis of this key intermediate by way of a Ritter reaction was a vital step in the sequence. Enantioselective Noyori hydrogenation reactions gave access to the chiral epoxides necessary to make the target compounds. Chemistry was developed for the selective dehalogenation of the 2-chloropyridyl group in the presence of a sensitive isoxazole unit to provide access to 1 .,10.1021/op1001462,2010-09-28,0.6594062894759188
Organic Letters,A Concise and Stereoselective Synthesis of Squalamine,[reaction: see text] A short and highly stereoselective synthesis of the novel steroid squalamine (1) was accomplished in nine steps from easily available methyl chenodeoxylcholanate 2. Our synthesis featured improved dehydrogenation of 4 followed by conjugate reduction to construct the trans AB-ring system and efficient asymmetric isopropylation of aldehyde 6 to introduce the C-24R-hydroxyl group.,10.1021/ol035062j,2003-08-15,0.6594051378605611
Synlett,Synthesis of Majusculamides A and B,"The synthesis of two marine lipodipeptides, majusculamides A and B, is described. The key feature of this synthesis is the stereoselective construction of an α-methyl-β-keto-carboxamide moiety.",10.1055/s-0037-1611805,2019-04-12,0.6593358893306224
Synlett,Asymmetric Formal Synthesis of Trichodermamides B and C,"Abstract An asymmetric formal synthesis of trichodermamides B and C was achieved in 15 steps based on a tyrosine ester chiral-pool approach. Key features of this synthesis include stereoselective construction of a cis-1,2-oxazadecaline core by an acid-mediated tandem deprotection–intramolecular oxy-Michael reaction, oxime ether formation via an N-bromination–elimination sequence, and diene construction by a palladium-catalyzed demonomethylcarbonation.",10.1055/s-0040-1720383,2021-07-21,0.6593323491484762
Tetrahedron,An Efficient Synthesis of Chiral Nonracemic Diamines: Application in Asymmetric Synthesis,,10.1016/s0040-4039(97)10578-0,1998-01-01,0.6593266088926314
Organic Letters,Stereoselective Synthesis of the Core Ring System of Lancifonins A–D,"A 5/5/7 tricyclic intermediate bearing an oxa-bridged hemiketal ring was successfully synthesized from dihydrocarvone in 14 steps, which is a common intermediate of various Schisandra nortriterpenoids. Subsequently, the core structure of lancifonins A–D, characterized by a 5/5/7/8 fused ring system, was constructed in seven steps. The route employs key transformations, including the aldol reaction, Mukaiyama hydration, Mn(III)-mediated cyclization, the Suzuki reaction, and McMurry coupling.",10.1021/acs.orglett.5c00263,2025-03-24,0.6593158665298134
Synlett,Synthesis of Ieodomycin D,A synthesis of the marine natural product ieodomycin D has been achieved in seven steps and 16% overall yield from commercially available pyridinium-1-sulfonate. The key synthetic step was a B -alkyl Suzuki–Miyaura cross-coupling reaction. The enantiomer of ieodomycin D was also prepared using the same synthetic strategy.,10.1055/s-0035-1562776,2016-07-14,0.6592983781663383
Organic Process Research & Development,A Scaleable Synthesis of Methyl 3-Amino-5-(4-fluorobenzyl)-2-pyridinecarboxylate,"A scaleable synthesis of methyl 3-amino-5-(4-fluorobenzyl)-2-pyridinecarboxylate ( 1b ), starting from 5-bromo-2-methoxypyridine ( 8 ) and 4-fluorobenzaldehyde ( 9 ), is described. Key steps in the process include lithium–bromine exchange of 8, addition of the resulting lithiate to aldehyde 9, regioselective nitration of pyridone 12, and Pd-catalyzed alkoxycarbonylation of bromopyridine 15b . Overall yield of the five-stage synthesis was 23%; intermediates 10, 12, 13, 15b, and final product 1b ·HCl were isolated as filterable solids. Compounds 1a,b are important intermediates in the synthesis of 7-benzylnaphthyridinones (e.g., 2 ) and related HIV-1 integrase inhibitors.",10.1021/op7001326,2007-09-01,0.659283050937008
Tetrahedron,Catalytic asymmetric synthesis of key intermediate for scytophycin C,,10.1016/j.tetlet.2015.12.051,2015-12-14,0.6592748467103836
Tetrahedron,"An efficient synthesis of 1,4-dideoxy-1,4-imino-d- and l-arabinitol and 1,4-dideoxy-1,4-imino-d- and l-xylitol from chiral aziridines",,10.1016/j.tetlet.2013.08.040,2013-08-20,0.6592731960792669
Tetrahedron,An efficient chiral synthesis of (+)-sesbanine,,10.1016/s0040-4039(00)92596-6,1980-01-01,0.6592731960792669
Tetrahedron,An efficient synthesis of chiral 2-( -tolylsulfinyl)-2-butenolides,,10.1016/s0040-4039(00)84484-6,1986-01-01,0.6592731960792669
Tetrahedron,An efficient chiral-pool synthesis of botryolide-E,,10.1016/j.tetlet.2012.08.019,2012-08-10,0.6592731960792669
Synlett,Total Synthesis of (+)-Cryptocaryanone A,"The first total synthesis of (+)-cryptocaryanone A is described. The synthesis features a Mukaiyama aldol reaction, one-pot saponification/lactonization sequences, and TsOH-assisted dihydropyrone formation as key steps.",10.1055/s-0032-1316580,2012-07-04,0.6591986667412018
Journal of Organic Chemistry,"Asymmetric Synthesis of (−)-Swainsonine, (+)-1,2-Di-<i>epi</i>-swainsonine, and (+)-1,2,8-Tri-<i>epi</i>-swainsonine","The asymmetric synthesis of (-)-swainsonine via a nonchiral pool route that involves the Sharpless epoxidation to induce chirality is reported. The key steps involve vinyl epoxide aminolysis, ring-closing metathesis, and intramolecular N-alkylation to prepare the indolizidine ring and a highly diastereoselective cis-dihydroxylation using AD-mix-alpha. This synthetic strategy also allowed for the diastereoselective synthesis of (+)-1,2-di-epi-swainsonine and (+)-1,2,8-tri-epi-swainsonine.",10.1021/jo025977w,2002-09-28,0.6591976470347978
Journal of Organic Chemistry,"A Formal Total Synthesis of (+)-Tetronolide, the Aglycon of the Tetrocarcins:  Enantio- and Diastereoselective Syntheses of the Octahydronaphthalene (Bottom-Half) and Spirotetronate (Top-Half) Fragments","A formal total synthesis of (+)-tetronolide, the aglycon of the tetrocarcins, has been achieved by virtue of the development of highly diastereo- and enantioselective syntheses of the bottom- and top-half fragments 4 and 5 reported herein. These fragments previously served as key intermediates in Yoshii's pioneering total synthesis of (+)-tetronolide. The synthesis of the bottom-half octahydronaphthalene unit 4 features the intramolecular Diels−Alder reaction of tetraenal 20 and proceeds in 17 steps and 5−6% yield from d -glyceraldehyde pentylidene acetal 8 . The synthesis of the spirotetronate fragment 5 features the highly enantioselective exo selective Diels−Alder reaction of triene 37 and chiral dienophile 25b and proceeds in 14 steps and 10% overall yield from cis -2-butene-1,4-diol ( 38 ). An enantioselective synthesis of Boeckman's top-half cyclohexene fragment 6 via the exo selective Diels−Alder reaction of diene 24 and dienophile 25a was also developed, but this route was deemed too inefficient for use in a projected total synthesis of the natural product. The syntheses of 5 and 6 provide important information on the utility of chiral dienophiles 25a and 25b in organic synthesis.",10.1021/jo970960c,1997-12-01,0.6591748028640981
Tetrahedron,"Urumamide, a novel chymotrypsin inhibitor with a β-amino acid from a marine cyanobacterium Okeania sp.",,10.1016/j.tetlet.2016.08.012,2016-08-05,0.6591587518881086
Angewandte Chemie International Edition,Eight‐Step Enantioselective Total Synthesis of (−)‐Cycloclavine,"Abstract The first enantioselective total synthesis of (−)‐cycloclavine was accomplished in 8 steps and 7.1 % overall yield. Key features include the first catalytic asymmetric cyclopropanation of allene, mediated by the dirhodium catalyst Rh 2 (S‐TBPTTL) 4 , and the enone 1,2‐addition of a new TEMPO carbamate methyl carbanion. An intramolecular strain‐promoted Diels–Alder methylenecyclopropane (IMDAMC) reaction provided a pivotal tricyclic enone intermediate with more than 99 % ee after crystallization. The synthesis of (−)‐ 1 was completed by a late‐stage intramolecular Diels–Alder furan (IMDAF) cycloaddition to install the indole.",10.1002/anie.201608820,2016-11-18,0.6591496804018404
Journal of Organic Chemistry,Total Synthesis of Phenanthroindolizidine Alkaloids by Combining Iodoaminocyclization with Free Radical Cyclization,"A concise and modular synthesis of phenanthroindolizidine alkaloids was achieved by combining iodoaminocylization with a free radical cyclization approach. The route described allowed the preparation of (±)-tylophorine, (±)-antofine, and (±)-deoxypergularinine in six steps. When commercially available l-prolinol was used as a chiral building block, (S)-(+)-tylophorine was also synthesized in 49% yield and >99% ee over five linear steps.",10.1021/acs.joc.6b01161,2016-06-17,0.6591484847979793
Organic Process Research & Development,"Industrial Synthesis of the Key Precursor in the Synthesis of the Anti-Influenza Drug Oseltamivir Phosphate (Ro 64-0796/002, GS-4104-02):  Ethyl (3<i>R</i>,4<i>S</i>,5<i>S</i>)-4,5-epoxy-3-(1-ethyl-propoxy)-cyclohex-1-ene-1-carboxylate","Starting from (−)-quinic acid, the title compound was synthesized in seven chemical steps and an overall yield of 35−38%. The route of the improved Gilead synthesis was not changed. However, significant improvements in each step led to a doubled overall yield, a 30% reduction in the number of unit operations, and an excellent quality (≥99%) of the resulting epoxide. A highly regioselective method for the dehydration of a quinic acid to a shikimic acid derivative and for the reduction of a cyclic ketal was found. Alternatively, the title compound was synthesized in six chemical steps and 63−65% yield from commercially available (−)-shikimic acid. Compared to the optimized quinic acid route, the production time was reduced by about 50%. The quality of epoxide produced from either natural product was equivalent. Therefore (−)-shikimic acid is the preferred raw material. The absolute configuration of the epoxide was determined by X-ray single crystal structure analysis and it was demonstrated that the epoxide was stereoisomerically pure.",10.1021/op9900176,1999-06-30,0.6591432828116274
Chemical Science,Bioinspired synthesis of pentacyclic onocerane triterpenoids,"The first chemical synthesis of pentacyclic onocerane triterpenoids has been achieved. A putative biomimetic tricyclization cascade is employed to forge a fused decalin-/oxepane ring system. The synthetic route proceeds to (+)-cupacinoxepin in seven steps and to (+)-onoceranoxide in eight steps in the longest linear sequence, when starting from geranyl chloride and (+)-sclareolide. The bioinspired epoxypolyene cyclization is supported by computational and enzymatic studies.",10.1039/c7sc03903d,2017-01-01,0.6591176567184479
Journal of Organic Chemistry,Integrated Cross-Coupling Strategy for an α-Carboline-Based Aurora B Kinase Inhibitor,"An efficient and practical synthetic process for an α-carboline-based Aurora B kinase inhibitor was achieved using an integrated Pd-catalyzed cross-coupling strategy. The process features a mild and efficient method for construction of the α-carboline core by employing a Pd-catalyzed sequence of Buchwald-Hartwig amination and intramolecular direct C-H arylation at the ortho position of an unsubstituted aniline moiety, which is a key functionality for further derivatization with a Suzuki coupling via Sandmeyer iodination. The process has eliminated expensive starting materials and column chromatography purifications and enabled considerable enhancement of the total yield from 11% to 48%.",10.1021/jo502489x,2015-01-23,0.659105858953512
Journal of Organic Chemistry,Total Synthesis of (+)-Epilupinine via An Intramolecular Nitrile Oxide-Alkene Cycloaddition,"Total synthesis of (+)-epilupinine was accomplished in nine steps and in 48% overall yield, in which INOC was used as the key step for the construction of the quinolizidine skeleton. We found that it was an extremely difficult task to prepare the key intermediates (R)-N-(3-nitropropyl)-2-vinylpiperidine or (R)-(2-vinylpiperid-1-yl)propanal by routine methods. Thus, by using Fukuyama's oxime synthesis, a general method was developed for highly efficient conversion of 3-(N,N-dialkylamino)propanols into 3-(N,N-dialkylamino)propanal oximes without using the corresponding aldehydes.",10.1021/jo101910r,2010-12-01,0.6590864540762615
Synlett,First Total Synthesis of MalvoneA and Formal Syntheses of Boryquinone and Hybocarpone Using a ConciseStrategy for Construction of Unsymmetrical Naphthoquinones,"The first total synthesis of malvone A (1) is presented in seven steps along with a nine-step formal synthesis of boryquinone (2) and an eleven-step formal synthesis of hybocarpone (3). The overall strategy, which accesses compounds 7-12 for the first time, employs an easily constructed α-tetralone, and it has significant implications for synthesis of the naphthoquinone portion of β-rubromycin (4) as well as a host of other unsymmetrical and differentially protected naphthoquinones.",10.1055/s-0028-1088134,2009-04-08,0.6590814761194204
Organic Letters,Asymmetric Total Synthesis of (−)-Lemnalemnane A,"The asymmetric total synthesis of lemnalemnane A, a rare rearranged sesquiterpenoid, has been accomplished in 13 steps from ( S )-carvone. The key features of the synthesis are the removal of the isopropenyl group derived from ( S )-carvone via a radical intermediate, the formation of the bicyclo[3.3.1]nonane skeleton using the Dieckmann condensation, the stereocontrolled construction of five continuous chiral centers by chemo- and stereoselective reduction and stereoselective introduction of the alkyne group, and the formation of the spirolactone moiety via a hemiacetal intermediate.",10.1021/acs.orglett.3c04314,2024-02-26,0.6590645099664455
Synthesis,Synthesis of a Cyclopent[g]isoquinoline Building Block for Fredericamycin A,"A new route to the DEF-ring building block of fredericamycin A has been elaborated. The five-step synthesis involves a photo-Wolff reaction as the key step and leads to carboxylic acid 2 in 27% overall yield, starting from the pyridine derivative 3. Two intermediates, the tricyclic ketones 6a and 7, are characterized by crystal structure analyses.",10.1055/s-0029-1218744,2010-04-15,0.659028859746838
Journal of Organic Chemistry,"A Concise Synthesis of (<i>2R,6R</i>)-Hydroxynorketamine","A concise synthesis of ( 2R,6R )-hydroxynorketamine was accomplished in eight steps, starting from commercially available materials. This synthesis features a cerium chloride-enhanced Stork–Danheiser reaction, an asymmetric reduction of ketone by the Corey–Bakshi–Shibata reaction, a signature Overman rearrangement, and a facial selective dihydroxylation of an electronically deficient olefin by RuCl 3 /NaIO 4 . The overall yield is 7.3% with 94.5% ee .",10.1021/acs.joc.4c01502,2024-11-01,0.6589974103016892
Journal of Organic Chemistry,Total Synthesis of Citrafungin A,"The antifungal natural product citrafungin A was synthesized using, as key steps, an asymmetric aldol reaction of a chiral oxazolidinone, diastereoselective alkylation of a chiral 1,3-dioxolan-2-one, semihydrogenation of an enyne, and selective methyl ester deprotection.",10.1021/jo801708q,2008-10-04,0.6589746151251036
Journal of the American Chemical Society,Biomimetic Synthesis of the Antimalarial Flindersial Alkaloids,"A biomimetic strategy for the synthesis of the antimalarial flindersial alkaloids is described. Flinderoles A, B, and C, desmethylflinderole C, isoborreverine, and dimethylisoborreverine were all synthesized in three steps from tryptamine. The key step is an acid-promoted dimerization of the natural product borrerine. This approach is thought to mirror the biosynthesis of these compounds.",10.1021/ja301387k,2012-04-10,0.6589312597454582
Synlett,"Synthesis of Novel 2,6-Diazaspiro[3.3]heptanes","A practical route to 2,6-diazaspiro[3.3]heptanes is described by way of reductive amination of a readily available aldehyde with primary amines or anilines. Cyclisation proceeds in high yield and the methods reported are amenable to either library or large-scale synthesis.",10.1055/s-2007-986650,2007-09-21,0.6589243807259577
Journal of Organic Chemistry,Modular and Practical Synthesis of 6-Substituted Pyridin-3-yl C-Nucleosides,"A novel modular and practical methodology for preparation of 6-substituted pyridin-3-yl C-nucleosides was developed. The Heck reaction of 2-chloro-5-iodopyridine with a 3'-TBDMS-protected glycal gave a 6-chloropyridin-3-yl nucleoside analogue, which was then desilylated, selectively reduced, and reprotected to give the TBDMS-protected 6-chloropyridin-3-yl C-2'-deoxyribonucleoside as a pure beta-anomer in a total yield of 39% over four steps. This key intermediate was then subjected to a series of palladium-catalyzed cross-coupling reactions, aminations, and alkoxylations to give a series of protected 1beta-(6-alkyl-, 6-aryl-, 6-hetaryl, 6-amino-, and 6-tert-butoxypyridin-3-yl)-2'-deoxyribonucleosides. 6-Unsubstituted pyridin-3-yl C-nucleoside was prepared by catalytic hydrogenation of the chloro derivative and 6-oxopyridine C-nucleoside by treatment of the 6-tert-butoxy derivative with TFA. Deprotection of all the silylated nucleosides by Et3N.3HF gave a series of free C-nucleosides (10 examples).",10.1021/jo0709504,2007-08-01,0.658917919677413
Journal of Organic Chemistry,"Asymmetric Synthesis of a 5,6,7,8-Tetrahydro-1,6-naphthyridine Scaffold Leading to Potent Retinoid-Related Orphan Receptor γt Inverse Agonist TAK-828F","An asymmetric synthesis of the tetrahydronaphthyridine scaffold of TAK-828F as a RORγt inverse agonist has been developed. The synthesis features a newly discovered atom-economical protocol for Heck-type vinylation of chloropyridine using ethylene gas, an unprecedented formation of dihydronaphthyridine directly from 2-vinyl-3-acylpyridine mediated by ammonia, and a ruthenium-catalyzed enantioselective transfer hydrogenation as key steps. This represents the first example of the enantioselective synthesis of a 5,6,7,8-tetrahydro-1,6-naphthyridine compound. The new synthesis is also free of chromatography or distillation purification processes and therefore qualifies for extension to large-scale manufacture.",10.1021/acs.joc.0c01311,2020-07-23,0.6589129373475682
Organic Process Research & Development,Process Development and Pilot-Scale Synthesis of Cefotetan,Strategies that were adopted during the process development of Cefotetan in order to achieve a cost-effective commercial-scale synthesis are described herein. These included replacement of the trifluoroacetic acid used for cleavage of the benzhydryl ester and the development of an alternative synthetic route. This work led to improvement of both the impurity profile and the yield of the process. The pilot-scale synthesis of Cefotetan is described in detail in the Experimental Section. The scaled-up process has been successfully used for the commercial manufacture of Cefotetan since 1983.,10.1021/op049914m,2004-11-01,0.6589032711365107
Organic Process Research & Development,Improved Synthesis and Impurity Identification of (<i>R</i>)-Lacosamide,"An improved synthesis of Lacosamide 1 with high purity has been developed. Critical parameters of each step were identified as well as the impurities generated. Moreover, a creative method to improve chiral purity and stability of the key intermediate ( R )-2-amino- N -benzyl-3-methoxypropionamide 10 by forming salt with an achiral acid (phosphoric acid) was discovered to ensure the chiral purity of ( R )-Lacosamide. Phosphoric acid was further developed for the deprotection of the Boc group.",10.1021/acs.oprd.8b00370,2019-03-08,0.6589018127517839
Synthesis,An Efficient Synthesis of Homogentisic Acid,,10.1055/s-1980-28931,1980-01-01,0.6588828051864445
Tetrahedron,An efficient synthesis of δ-aminolevulinic acid (ALA) and its isotopomers,,10.1016/s0040-4039(96)02419-7,1997-02-01,0.6588828051864445
Tetrahedron,An efficient synthesis of sugar pyruvic acid acetals,,10.1016/s0040-4039(00)99475-9,1989-01-01,0.6588828051864445
Tetrahedron,"Development of a scalable synthesis of P7C3-A20, a potent neuroprotective agent",,10.1016/j.tetlet.2013.06.024,2013-06-13,0.6588808600829533
Organic Process Research & Development,"Development of a Scalable Synthesis of 4-Aminopyrimidin-5-ol, a Versatile Intermediate","A robust process for the preparation of multigram quantities of 4-aminopyrimidin-5-ol ( 5 ) in good yield from an inexpensive and readily available pyrimidine starting material is described. An initial evaluation of the reported literature route for this material utilizing a de novo pyrimidine synthesis provided safety concerns over the scalability of several intermediates. In addition, a number of steps proceeded in mediocre yield, and involved chromatographic separations for the desired products. The newly developed route mitigates the safety concerns, reduces the number of steps from five to three, avoids column chromatography, leads to an 8-fold improvement in yield, and utilizes reagents, which are recognized to be more environmentally benign.",10.1021/acs.oprd.5b00074,2015-05-21,0.6588778293120412
Journal of the American Chemical Society,Enantioselective Total Synthesis of Lycopodine,"The first enantioselective total synthesis of lycopodine has been completed. Key steps include a highly diastereoselective organocatalyzed cyclization of a keto sulfone to establish the key C7 and C8 stereocenters and a tandem 1,3-sulfonyl shift/intramolecular Mannich cyclization to form the tricyclic core.",10.1021/ja803613w,2008-06-27,0.6588694099559739
Organic Process Research & Development,Route Selection and Process Development for a 5-Piperazinylquinaldine Derivative for the Treatment of Depression and Anxiety,"1-(3-{2-[4-(2-Methyl-5-quinolinyl)-1-piperazinyl]ethyl}phenyl)-2-imidazolidinone, 1, was identified as a potential drug for the treatment of depression and anxiety. Herein is described the work carried out to select the manufacturing route and the process research studies to optimize the key stages of route B. A particular focus is given to the genotoxic impurities, related to this route, as one of the intermediates of the manufacturing route was genotoxic and many genotoxic impurities can be formed in the process. Quality by Design principles were applied for the definition of the control strategy of these impurities.",10.1021/op200140v,2011-09-05,0.6588053997557779
Organic Letters,Total Synthesis of Pseudouridimycin,"Pseudouridimycin ( 1 ), a potent antibiotic against both Gram-positive and Gram-negative bacteria including multi-drug-resistant strains with a new mode of action isolated from Streptomyces sp ., was synthesized by a convergent strategy from 5′-amino-pseudouridine 5 and N -hydroxy-dipeptide 26 in 23% total yield. The key intermediate 26 was synthesized by hydroxylaminolysis of the nitrone derived from glutamine and subsequent glycylation with glycine chloride. The synthetic method provides an efficient and practical way for the synthesis of N -hydroxylated peptidyl nucleoside.",10.1021/acs.orglett.1c03914,2022-01-10,0.6587805103226426
European Journal of Organic Chemistry,Efficient Synthesis of Bis(5‐arylfuran‐2‐yl)methane Scaffolds Utilizing Biomass‐Derived Starting Materials,"Abstract A new synthetic route utilizing biomass‐derived furans as a starting material for the production of bis(5‐arylfuran‐2‐yl)methane scaffolds was developed. Decarboxylative cross‐coupling of 5‐hydroxymethylfuroic acid (HMFA) was studied in detail with overall good yields. Acid‐catalyzed self‐condensation was optimized to produce the target structures in excellent yields. Overall, this report introduces a new expedient synthesis to obtain bis(furyl) methane scaffolds that avoids the use of protecting groups and highlights the utilization of renewable carbon sources as starting materials.",10.1002/ejoc.202101571,2022-02-11,0.6587799535088706
Organic Letters,An Enantioselective Synthesis of Cryptocarya Diacetate,"[reaction: see text]. The enantioselective synthesis of cryptocarya diacetate has been achieved in 10 steps from ethyl sorbate. The route relies upon an enantio- and regioselective Sharpless dihydroxylation and a palladium-catalyzed reduction to form a delta-hydroxy-1-enoate, which was subsequently converted into a benzylidene-protected 3,5-dihydroxy carboxylic ester. This ester was converted into cryptocarya diacetate in 14% overall yield via an allylation and methathesis ring closure reaction sequence.",10.1021/ol016399t,2001-07-19,0.6587605230240025
Synlett,"Asymmetric Synthesis of Conformationally Constrained <i>trans</i>-2,3-Piperidinedicarboxylic Acid Derivatives","An efficient asymmetric synthesis of conformationally constrained (2S,3S)-piperidinedicarboxylic acid derivatives starting from l-aspartic acid β-tert-butyl ester and 3-chloro-2-(chloromethyl)-1-propene is described. The key steps involve N-alkylation of the aspartic acid ester followed by a stereoselective enolate intra­molecular cyclization (>95:5 dr). Various synthetic strategies were explored to achieve the cyclopropanation of the resulting olefin, ­including the Simmons-Smith reaction and palladium-catalyzed cyclopropanation.",10.1055/s-2007-968029,2007-02-01,0.6587361152047283
Tetrahedron,Synthesis of 2-aryl-3-phenylindones and a new simple route to pentaphene,,10.1016/s0040-4039(01)89252-2,1965-01-01,0.6587321284798305
Synlett,Synthetic Studies Directed toward Kaitocephalin: A Highly Stereocontrolled Route to the Right-Hand Pyrrolidine Core,"A highly stereocontrolled method for the construction of the right-hand segment of kaitocephalin, an antagonist of AMPA/KA and NMDA glutamate receptors, has been developed employing palladium-catalyzed cyclization of an oxiranylacrylate at the quaternary center as the key step.",10.1055/s-2008-1042801,2008-02-26,0.6587127842557967
Journal of Organic Chemistry,Stereoselective Total Synthesis of Etnangien and Etnangien Methyl Ester,"A highly stereoselective joint total synthesis of the potent polyketide macrolide antibiotics etnangien and etnangien methyl ester was accomplished by a convergent strategy and proceeds in 23 steps (longest linear sequence). Notable synthetic features include a sequence of highly stereoselective substrate-controlled aldol reactions to set the characteristic assembly of methyl- and hydroxyl-bearing stereogenic centers of the propionate portions, an efficient diastereoselective Heck macrocyclization of a deliberately conformationally biased precursor, and a late-stage introduction of the labile side chain by means of a high-yielding Stille coupling of protective-group-free precursors. Along the way, an improved, reliable protocol for a Z-selective Stork-Zhao-Wittig olefination of aldehydes was developed, and an effective protocol for a 1,3-syn reduction of sterically particularly hindered beta-hydroxy ketones was devised. Within the synthetic campaign, a more detailed understanding of the intrinsic isomerization pathways of these labile natural products was elaborated. The expedient and flexible strategy of the etnangiens should be amenable to designed analogues of these RNA-polymerase inhibitors, thus enabling further exploration of the promising biological potential of these macrolide antibiotics.",10.1021/jo100201f,2010-03-24,0.6587107887151917
Synthesis,"A Three-Step Protocol towards N-8-(2,2-Dimethoxyethyl)-2-methylsulfanylpyrido[2,3-d]pyrimidin-7-one","An efficient high-yielding three-step synthesis of N -8-(2,2-dimethoxyethyl)-2-methylsulfanylpyrido[2,3- d ]pyrimidin-7-one is reported. The route utilises a Heck coupling as the key step.",10.1055/s-0036-1588364,2016-11-28,0.6586764155885861
Organic Letters,"A Rapid, Asymmetric Synthesis of the Decahydrofluorene Core of the Hirsutellones","A tandem ketene-trapping/Diels-Alder cyclization sequence was the pivotal transformation in an efficient, asymmetric synthesis of a decahydrofluorene tricyclic structure possessing eight stereogenic centers and key features of the hirsutellone class of antitubercular natural products. The hirsutellone-like beta-keto ester that was fashioned by this sequence (13 steps; 6% overall yield) demonstrated significant inhibitory activity against Mycobacterium tuberculosis. The mechanism of action of this antitubercular compound is not yet known.",10.1021/ol802768p,2009-01-02,0.6586755133371058
Angewandte Chemie International Edition,Convergent Total Synthesis of Kalmanol,Kalmanol (1) is the first isolated kalmane-type grayanoid featuring a highly oxidized 5/8/5/5 tetracyclic carbon skeleton and 9 contiguous stereocenters. We have accomplished the efficient and asymmetric total synthesis of 1 in 16 steps from known compounds (20 steps from commercially available starting materials) by a modular synthetic strategy. A tetracyclic intermediate was prepared in a convergent manner through a Grignard reaction and a subsequent ring-closing metathesis reaction of two enantiomerically enriched fragments. The polyhydroxy groups were introduced by late-stage stereo- and regioselective oxidations.,10.1002/anie.202420507,2024-11-27,0.6586659056010172
Synlett,"Total Synthesis of Avermectin B1a: Planning of the Synthesis and Preparation of the C1-C10 ""Southern"" Hydrobenzofuran Fragment","All articles of this category A strategy for the synthesis of the anthelmintic macrolide avermectin B1a ( 1 ) is presented, involving a highly convergent approach necessitating the preparation and coupling of five key fragments. The C1-C10 hydrobenzofuran unit 2 was obtained in 14 steps from a previously reported, optically pure cyclohexanone derivative 3 .",10.1055/s-1990-21078,1990-01-01,0.6586550172839326
Journal of Organic Chemistry,Synthesis of (<i>E</i>)-4-Hydroxydimethylallyl Diphosphate. An Intermediate in the Methyl Erythritol Phosphate Branch of the Isoprenoid Pathway,"The syntheses of (E)-1-hydroxy-2-methyl-2-buten-4-yl diphosphate ((E)-4-hydroxydimethylallyl diphosphate, HDMAPP), an intermediate in the methyl erythritol phosphate pathway, and (E)-[4-(2)H]HDMAPP were accomplished in two steps from (E)-4-chloro-2-methyl-2-butenal. The synthetic route is easily adaptable for the facile incorporation of tritium at C-4 of the diphosphate.",10.1021/jo0258453,2002-05-31,0.6586499092907951
Organic Letters,Total Synthesis of (−)-Kainic Acid via Intramolecular Michael Addition: A Second-Generation Route,A total synthesis of (-)-kainic acid starting from the commercially available 2-azetidinone is described. The key delta-lactone intermediate was concisely prepared from the commercially available azetidinone through the Reformatsky-type reaction and an introduction of a glycine moiety. The construction of the functionalized pyrrolidine ring was executed by a one-pot sequential elimination-Michael addition protocol of a beta-amino-delta-lactone intermediate with high diastereoselectivity.,10.1021/ol800328q,2008-04-11,0.658637797621841
Tetrahedron,A new route to 3-(2-vinylphenyl)-2-methyl-2H-isoquinolin-1-ones and benzo[c]phenanthridines: total synthesis of fagaronine,,10.1016/s0040-4039(02)01013-4,2002-07-01,0.6586342037414427
Organic Process Research & Development,An Improved Commercial Process for the Preparation of Lifitegrast,"A straightforward, efficient, and scalable commercial manufacturing process was developed for the ophthalmic anti-inflammatory drug lifitegrast via a novel ester intermediate from commercially available starting materials. Lifitegrast (Xiidra) was approved by the FDA on July 11, 2016, for the treatment of signs and symptoms of dry eye, a syndrome called keratoconjunctivitis sicca. The breakthrough step of this new process is the discovery of an N -Boc deprotection reaction that simultaneously transesterifies an intermediate to a new ester by using oxalyl chloride, which has favorable isolation properties. As a result of transesterification, the hydrolysis of the new ester intermediate occurs under milder conditions, which improves the quality of the product by reducing racemization. Lifitegrast prepared from this new process complied with the quality guidelines, as per the International Council for Harmonization (ICH). By using this new process, lifitegrast was produced on a 2 kg scale with an overall yield of 66%.",10.1021/acs.oprd.4c00356,2024-12-06,0.6586052499014852
Tetrahedron,"A novel synthesis of (3R,4R)-4-acetoxy-3-[(R)-1-(t-butyldimethylsilyloxy)ethyl]-2-azetidinone, the versatile key intermediate of carbapenem synthesis, from (S)-ethyl lactate",,10.1016/s0040-4039(00)85317-4,1986-01-01,0.6585933822931691
Organic Letters,"Total Synthesis of Cyclomarin A, a Marine Cycloheptapeptide with Anti-Tuberculosis and Anti-Malaria Activity","An efficient synthetic protocol for the stereoselective synthesis of cyclomarin A is reported. Key steps in the syntheses of the building blocks are an asymmetric chelate-enolate Claisen rearrangement, an asymmetric hydrogenation, and highly diastereoselective additions of organozinc and -titanium reagents.",10.1021/acs.orglett.5b03292,2015-12-23,0.6585857573196303
Organic Letters,Highly Substituted Oxabicyclic Derivatives from Furan: Synthesis of (±)-Platensimycin,A stereocontrolled approach to a key platensimycin intermediate was achieved from a commercially available furylcarboxylate. Key to our approach is the highly efficient formal [4 + 3] cyclocondensation of a substituted furan with tetrabromocyclopropene along with an intramolecular γ-alkylation to construct the final ring of the caged intermediate.,10.1021/ol2005775,2011-03-31,0.6584991750063913
Synlett,The Synthesis of the New C-Nucleoside 6-Deazaformycin B,"The synthesis of the 6-deaza analogue of formycin B is described, through the condensation of lithiated 4-methoxy-2-methyl-3-trifluoroacetamidopyridine with a suitably protected ribonolactone, dehydration of the resulting hemiacetal, reduction and subsequent ring closure followed by protecting group manipulation.",10.1055/s-2007-1000870,2008-01-01,0.6584903447380087
Journal of the American Chemical Society,Atroposelective Negishi Coupling Optimization Guided by Multivariate Linear Regression Analysis: Asymmetric Synthesis of KRAS G12C Covalent Inhibitor GDC-6036,"An efficient asymmetric synthesis of a potent KRAS G12C covalent inhibitor, GDC-6036 ( 1 ), is reported. The synthesis features a highly atroposelective Negishi coupling to construct the key C–C bond between two highly functionalized pyridine and quinazoline moieties by employing a Pd/Walphos catalytic system. Statistical modeling by comparing computational descriptors of a range of Walphos chiral bisphosphine ligands to a training set of experimental results was used to inform the selection of the best ligand, W057-2, which afforded the desired Negishi coupling product ( R a )-3 in excellent selectivity. A subsequent telescoped reaction sequence of alkoxylation, global deprotection, and acrylamide formation, followed by a final adipate salt formation, furnished GDC-6036 ( 1 ) in 40% overall yield from starting materials pyridine 5 and quinazoline 6 .",10.1021/jacs.2c09917,2022-11-03,0.6584879988046717
Journal of Organic Chemistry,Six-Step Synthesis of (±)-Lysergic Acid,"This article describes a concise synthesis of lysergic acid from simple aromatic precursors. The successful strategy relies on the coupling, dearomatization, and cyclization of a halopyridine with a 4-haloindole derivative in 6 total synthetic steps from commercial starting materials. In addition to highlighting the advantages of employing dearomative retrosynthetic analysis, the design is practical and anticipated to enable the synthesis of novel neuroactive compounds as exemplified by the synthesis of a novel natural product derivative, 12-chlorolysergic acid.",10.1021/acs.joc.2c02564,2023-01-30,0.6584845734951205
Tetrahedron,"A three-step synthesis of 4-(4-iodo-1H-pyrazol-1-yl)piperidine, a key intermediate in the synthesis of Crizotinib",,10.1016/j.tetlet.2011.12.044,2011-12-16,0.658455339761184
Organic Letters,"Total Synthesis of (+)-Spongistatin 1. An Effective Second-Generation Construction of an Advanced EF Wittig Salt, Fragment Union, and Final Elaboration","A stereocontrolled, total synthesis of (+)-spongistatin 1 (1) has been achieved. Union of a second-generation EF Wittig salt (+)-3 with the advanced ABCD aldehyde (-)-4, followed by regioselective macrolactonization and global deprotection afforded (+)-spongistatin 1 (1). The longest linear sequence, 29 steps, proceeded in 0.5% overall yield.",10.1021/ol034037a,2003-02-05,0.6584534241212068
Organic Process Research & Development,A Scaleable Synthesis of BAY 43-9006:  A Potent Raf Kinase Inhibitor for the Treatment of Cancer,"Urea 3 ( BAY 43 - 9006 ), a potent Raf kinase inhibitor, was prepared in four steps with an overall yield of 63%. Significant process research enabled isolation of each intermediate and target without chromatographic purification, and overall yield increases >50% were observed compared to those from previous methods. This report focuses on improved synthetic strategies for production of scaled quantities of 3 for preclinical, toxicological studies. These improvements may be useful to assemble other urea targets as potential therapeutic agents to combat cancer.",10.1021/op020205n,2002-09-20,0.6584326059231562
Synthesis,<i>C</i>-Acylation of Nitromethane. A Synthetic Route to α-Nitroketones,,10.1055/s-1978-24791,1978-01-01,0.6584250739666027
Angewandte Chemie International Edition,Total Synthesis of Polyoxygenated Cembrenes,"A convergent approach for the stereoselective construction of polyoxygenated cembrenes is reported. Key steps in the synthesis are an asymmetric domino multicomponent allylation, a modified Myers α-alkylation, and a ring-closing metathesis.",10.1002/anie.200800626,2008-06-04,0.6584244279635278
Chemical Science,Synthesis of flinderoles B and C by a gold-catalyzed allene hydroarylation,"The recent development of new gold(I) catalysis methodologies has opened the door to new disconnections for the total synthesis of bioactive complex molecules. Below is described the application of a gold(I)-catalyzed hydroarylation of an allene with indole toward the total synthesis of flinderoles B-C, members of a new class of antimalarial bisindole alkaloids isolated from plants of the Flindersia genus. The key gold(I) step establishes both the pyrrolidine and isobutenyl functionalities unique to these compounds. Other important steps of the synthesis include a convergent Horner-Wadsworth-Emmons olefination to construct the bridging alkene and a new strategy for α-indole enolate alkylations.",10.1039/c1sc00290b,2011-01-01,0.6584178691060899
Synlett,Synthesis of the C14-C29 Segment of Amphidinolide U Utilizing a Tandem Dihydroxylation-S<sub>N</sub>2 Cyclization Protocol,"The synthesis of the C14-C29 subunit of amphidinolide U is described. The key steps include the trans-2,5-disubstituted tetrahydrofurans via a highly diastereoselective and high yielding tandem dihydroxylation-SN2 cyclization, Wittig reaction, and Nozaki-Hiyama-Kishi coupling reaction.",10.1055/s-2008-1042931,2008-03-20,0.6584028331616464
Angewandte Chemie International Edition,An Efficient Synthesis of Lactacystin β‐Lactone,"A key step in the synthesis of lactacystin β-lactone (3), an inhibitor of the 20 S proteasome, was the ammonia-free reductive aldol reaction of pyrrole 1 to form 2 with complete anti selectivity. This route to 3 takes just 13 steps (14 % overall yield) and allows the late-stage stereoselective introduction of a methyl group at C4, which is crucial for the production of analogues. Boc=tert-butoxycarbonyl.",10.1002/anie.200453843,2004-04-16,0.6583976874529691
European Journal of Organic Chemistry,"Asymmetric Total Synthesis of (+)‐6‐<i>epi</i>‐Castanospermine by the Stereoselective Formation of a <i>syn,anti</i> Acetylenic 2‐Amino‐1,3‐diol Stereotriad",Abstract The asymmetric total synthesis of (+)‐6‐ epi ‐castanospermine ( 1 ) is described herein. In this synthesis the diastereoselective addition of a racemic allenylzinc reagent to an enantiopure α‐alkoxy‐ tert ‐butylsulfinylimine is the key step and is followed by the formation of a piperidine ring by ring‐closing metathesis and subsequent syn ‐dihydroxylation of an alkene.,10.1002/ejoc.201000202,2010-04-08,0.6583817237579874
Journal of Organic Chemistry,Enantioselective Synthesis of SNAP-7941: Chiral Dihydropyrimidone Inhibitor of MCH1-R,"An enantioselective synthesis of SNAP-7941, a potent melanin concentrating hormone receptor antagonist, was achieved by using two organocatalytic methods. The first method utilized to synthesize the enantioenriched dihydropyrimidone core was the Cinchona alkaloid-catalyzed Mannich reaction of beta-keto esters to acylimines and the second was the chiral phosphoric acid-catalyzed Biginelli reaction. Completion of the synthesis was accomplished via selective urea formation at the N3 position of the dihydropyrimidone with the 3-(4-phenylpiperidin-1-yl)propylamine side chain fragment. The synthesis of SNAP-7921 highlights the utility of asymmetric organocatalytic methods in the construction of an important class of chiral heterocycles.",10.1021/jo801463j,2008-09-04,0.6583813421654867
Journal of Organic Chemistry,"[5C + 1S] Annulation:  A Facile and Efficient Synthetic Route toward Functionalized 2,3-Dihydrothiopyran-4-ones","[reaction: see text] A facile and efficient synthetic route toward highly substituted 2,3-dihydrothiopyran-4-ones 2 has been developed via a formal [5C + 1S] annulation of readily available alpha-alkenoyl ketene-(S,S)-acetals 1 with sodium sulfide nonahydrated salt (Na2S x 9H2O) and utilized in the synthesis of 2-(4-chlorophenyl)-6-(morpholin-4-yl)-4H-thiopyran-4-one 5l, an inhibitor of DNA-dependent protein kinase (DNA-PK).",10.1021/jo052032g,2005-11-24,0.6583278497990184
Journal of Organic Chemistry,Formal Synthesis of (±)-Cycloclavine,An efficient formal synthesis of (±)-cycloclavine is achieved in seven steps and 27% overall yield from the known 2-(4-bromo-1-tosyl-1H-indol-3-yl)acetaldehyde. Key features include an iron(III)-catalyzed aza-Cope-Mannich cyclization and an intramolecular Heck reaction or a self-terminating 6-exo-trig aryl radical-alkene cyclization.,10.1021/jo4023588,2013-11-27,0.6582864755892689
Journal of the American Chemical Society,En Route to an Efficient Catalytic Asymmetric Synthesis of AS-3201,"A catalytic asymmetric synthesis of AS-3201 via catalytic asymmetric amination with a novel lanthanum−amide complex is described. The amination reaction proceeded efficiently with as little as 1 mol % of catalyst loading, allowing for an efficient access to the key intermediate for the synthesis of AS-3201, a potent aldose reductase inhibitor.",10.1021/ja0752585,2007-08-28,0.6582805499101931
Journal of the American Chemical Society,Enantioselective Total Synthesis of (−)-Taxol,"Enantioselective total synthesis of taxol has been accomplished. Coupling reaction of the optically pure A-ring hydroxy aldehyde with the aromatic C-ring fragment followed by Lewis acid mediated eight-membered B-ring cyclization gave the desired ABC endo-tricarbocycle. The C-ring moiety of this product was reduced under Birch conditions to the cyclohexadiene derivative, which was oxygenated by singlet oxygen from the convex β-face to give the C4β,C7β-diol stereoselectively. For introduction of the C19-methyl, the cyclopropyl ketone was prepared via cyclopropanation of the C-ring allylic alcohol or conjugate addition of a cyano group to the C-ring enone. Reductive cleavage of the cyclopropane ring followed by isomerization of the resulting enol to the corresponding ketone gave the crucial synthetic intermediate containing the C19-methyl group. Regioselective transformation of three hydroxyl groups of this intermediate, conversion of the C4-carbonyl group to the allyl chloride, and introduction of the C10-oxygen functionality afforded a precursor for D-ring construction. Dihydroxylation of the allyl chloride moiety followed by basic treatment of the resulting diol gave a fully functionalized taxol skeleton. Functional group manipulation of this product including attachment of the C13 side chain provided (−)-taxol.",10.1021/ja9939439,2000-04-01,0.6582799098356138
Journal of Organic Chemistry,Synthesis of Spiropiperidine Lactam Acetyl-CoA Carboxylase Inhibitors,"The synthesis of 4',6'-dihydrospiro[piperidine-4,5'-pyrazolo[3,4-c]pyridin]-7'(2'H)-one-based acetyl-CoA carboxylase inhibitors is reported. The hitherto unknown N-2 tert-butyl pyrazolospirolactam core was synthesized from ethyl 3-amino-1H-pyrazole-4-carboxylate in a streamlined 10-step synthesis requiring only one chromatography procedure. The described synthetic strategy provides pyrazolo-fused spirolactams from halogenated benzylic arenes and cyclic carboxylates. Key steps include a regioselective pyrazole alkylation providing the N-2 tert-butyl pyrazole and a Curtius rearrangement under both conventional and flow conditions to install the hindered amine via a stable and isolable isocyanate. Finally, a Parham-type cyclization was used to furnish the desired spirolactam. An analogous route provided efficient access to the related N-1 isopropyl lactam series. Elaboration of the lactam cores via amidation enabled synthesis of novel ACC inhibitors and the identification of potent analogues.",10.1021/jo3014808,2012-11-05,0.6582613883377743
Organic Process Research & Development,A Robust Kilo-Scale Synthesis of Doravirine,Doravirine is non-nucleoside reverse transcriptase inhibitor (NNRTI) currently in phase III clinical trials for the treatment of HIV infection. Herein we describe a robust kilo-scale synthesis for its manufacture. The structure and origin of major impurities were determined and their downstream fate-and-purge studied. This resulted in a redesign of the route to introduce the key nitrile functionality via a copper mediated cyanation which allowed all impurities to be controlled to an acceptable level. The improved synthesis was scaled to prepare ∼100 kg batches of doravirine to supply all preclinical and clinical studies up to phase III. The synthesis affords high-quality material in a longest linear sequence of six steps and 37% overall yield.,10.1021/acs.oprd.6b00163,2016-07-05,0.6582539695269028
Journal of Organic Chemistry,Enantioselective Synthesis of Dideoxy-tetrafluorinated Hexoses,"Carbohydrates typically have low affinities to protein binding sites, and the development of carbohydrate mimetics with improved binding is therefore of interest. Tetrafluorination of monosaccharides is one of the strategies currently under investigation for that purpose. The synthesis of the required tetrafluorinated monosaccharides is achieved by a fluorinated building block approach. The enantioselective synthesis of tetrafluorinated hexose derivatives is described here, in both pyranose and furanose forms. In particular, the optimization of the enantioselective synthesis of the previously reported 2,3-dideoxy-2,2,3,3-tetrafluoro-d-threo-hexopyranose 3, 2,3-dideoxy-2,2,3,3-tetrafluoro-d-threo-hexofuranose 4, and 2,3-dideoxy-2,2,3,3-tetrafluoro-d-erythro-hexopyranose 5 is described as is the synthesis of two novel sugar derivatives, 3,4-dideoxy-3,3,4,4-tetrafluoro-d-threo-hexopyranose 6 and 3,4-dideoxy-3,3,4,4-tetrafluoro-d-erythro-hexopyranose 7. The key step of all syntheses is a perfluoroalkyl lithium-mediated C-C bond formation, either intramolecular or intermolecular, which proceeds in good to excellent yields. NMR and X-ray crystallographic analyses of the tetrafluorinated methyl pyranoside derivatives confirm their (4)C1 conformation.",10.1021/acs.joc.6b00302,2016-03-25,0.6582527143476101
Synthesis,A Convergent Approach for the Synthesis of C14–C26 Fragment of Anticancer Drug Eribulin Mesylate,"Abstract The stereoselective synthesis of C14–C26 fragment of eribulin is reported in a convergent way by coupling of fragment C14–C19 with fragment C20–C26 that are accessible from commercially available raw materials crotonic acid and 1,4-butanediol. The key steps involved in this practical approach are Hosomi–Sakurai asymmetric alkylation, Maruoka allylation, Noyori reduction, silver-catalyzed one-pot rearrangement, and intramolecular cyclization.",10.1055/a-2202-5597,2023-11-02,0.6582494159424785
Tetrahedron,A new “5+1” route to arenes. Application to the facile synthesis of D4-symmetric chiral porphyrins,,10.1016/s0040-4039(00)77145-0,1994-04-01,0.6582459646818704
Angewandte Chemie International Edition,"Total Synthesis of Notoamides F, I, and R and Sclerotiamide","The total synthesis of the natural indole alkaloids (+)-notoamide F, I, and R and (-)-sclerotiamide is described. The four heptacyclic compounds were synthesized in 10-12 steps in a convergent and highly stereoselective manner from the readily available Seebach acetal. Key steps of the synthesis include a stereoselective oxidative aza-Prins cyclization to construct the bicyclo[2.2.2]diazaoctane, and a cobalt-catalyzed radical cycloisomerization to create the cyclohexenyl ring.",10.1002/anie.201604754,2016-07-22,0.6582414922226353
Organic Process Research & Development,Kilogram-Scale Synthesis of 2′-<i>C</i>-Methyl-<i>arabino</i>-Uridine from Uridine via Dynamic Selective Dipivaloylation,"We report a practical 3′,5′-diprotection strategy suitable for the kilogram-scale preparation of 2′- C -methyl- arabino -uridine, a key intermediate in the synthesis of the HCV NS5B inhibitor uprifosbuvir. Starting from uridine, dipivaloylation afforded an ∼2:1 mixture of 3′,5′- and 2′,5′-dipivaloyluridine. Subjecting this mixture to TEMPO/bleach oxidation promoted a dynamic acylation migration–selective oxidation to afford the 2′-ketone in 65% yield. Alternatively, treatment with 1 equiv of BF 3 etherate led to the crystallization-driven equilibration and precipitation of 3′,5′-dipivaloyluridine·BF 3 complex in a >50:1 ratio. After salt break, this mixture was oxidized in the presence of TEMPO/AcOOH to afford the 2′-ketone in 90% yield. Subsequent α-facial-selective methylation with MeMgBr/MnCl 2 afforded 3′,5′-dipivaloylated 2′- C -methyl- arabino -uridine 12 . This three-step process was successfully demonstrated on a multikilogram scale to afford the key intermediate for the manufacture of uprifosbuvir.",10.1021/acs.oprd.1c00175,2021-07-28,0.6582398159775283
Journal of Organic Chemistry,Enantioselective Total Synthesis of (+)-Eutypoxide B,"The enantioselective synthesis of (+)-eutypoxide B, a metabolite isolated from the culture medium of the fungus Eutypa lata, is described. Two highly stereoselective and efficient sequencial 1,4-additions to enone systems, derived from d -(−)-quinic acid, are the key to the synthesis. The synthesis of a diastereoisomer of (+)-eutypoxide B, was also accomplished.",10.1021/jo9617326,1997-06-13,0.658218014425395
Synthesis,A Stereodivergent Route to Four Stereoisomeric 3′-Acetoxycyclopentenylglycine Derivatives,A short and efficient synthetic route to four stereoisomeric 3′-acetoxycyclopentenylglycine derivatives from l-serine has been developed. The method features a stereoselective conjugate addition and ring-closing metathesis as key steps.,10.1055/s-0031-1289645,2011-12-14,0.6582076204306829
Synthesis,The First Total Synthesis of Pectinolides D and E and Total Synthesis of Pectinolides A and C,"The first total synthesis of pectinolides D and E and total synthesis of pectinolides A and C was achieved from a hitherto unknown common key building block prepared from readily available d -mannitol. Key reactions involved in the synthesis are Red-Al reduction of an epoxy alcohol, enantioselective Noyori reduction of ynones, aldehyde–alkyne coupling, and Still–Genari cis -olefination.",10.1055/s-0034-1378912,2014-11-14,0.6581898727011486
Journal of Organic Chemistry,Synthetic Study toward Ecteinascidin 743: Concise Construction of the Diazabicyclo[3.3.1]nonane Skeleton and Assembly of the Pentacyclic Core,"Synthesis of the pentacyclic core of ecteinascidin 743 is described. This synthesis features concise construction of the diazabicyclo[3.3.1]nonane skeleton using gold(I)-catalyzed one-pot keto amide formation, acid-promoted enamide formation, and oxidative Friedel-Crafts cyclization as the key steps.",10.1021/jo100788j,2010-06-17,0.6581850542653456
Tetrahedron,New chiral synthetic intermediate for prostaglandins,,10.1016/s0040-4039(00)61103-6,1992-09-01,0.6581652492451946
Organic Letters,Pyrroloiminoquinone Alkaloids: Total Synthesis of Makaluvamines A and K,"Herein, an efficient, scalable, and concise approach to an advanced pyrroloiminoquinone synthetic intermediate ( 6b ) by way of a Larock indole synthesis is reported. The synthetic utility of this intermediate is demonstrated by its ready conversion to makaluvamines A ( 1 ) and K ( 4 ).",10.1021/acs.orglett.3c00350,2023-03-13,0.658131170416769
Organic Process Research & Development,A New and Improved Synthesis of Bidisomide,"Bidisomide, an antiarrhythmic and defibrillating agent, has been synthesized by a new approach. One of the key intermediates in this synthesis is 2-( N -isopropyl- N -allylamino)ethyl chloride. The distinct advantages of this new process over the existing one are described.",10.1021/op010217t,2001-08-22,0.6581153577113728
Organic Letters,"A New Strategy toward the Total Synthesis of Stachyflin, A Potent Anti-Influenza A Virus Agent:  Concise Route to the Tetracyclic Core Structure","[reaction: see text] A new strategy directed toward the total synthesis of stachyflin, a potent and novel anti-influenza A virus agent isolated from a microorganism, has been presented through the enantioselective synthesis of the tetracyclic core structure. The synthetic method features a BF(3) x Et(2)O-induced domino epoxide-opening/rearrangement/cyclization reaction as the key step.",10.1021/ol0271032,2002-11-16,0.658102102047335
Tetrahedron,"An efficient synthesis of chiral, nonracemic isopropyl alkenylmethylphosphinates via palladium route",,10.1016/s0040-4039(00)95287-0,1989-01-01,0.658093650611514
European Journal of Organic Chemistry,A Scalable Synthesis of the Antidepressant Agomelatine by a Tandem Allylic Chlorination–Isomerization Process,"Abstract A concise, scalable, and industrially applicable process for the synthesis of the antidepressant agomelatine is described. The process relies on a tandem allylic chlorination–isomerization sequence, on a tetralone‐derived allyl carbinol, as the key transformation. The target compound is obtained in five steps from commercially available 7‐methoxy‐1‐tetralone, in 52.3 % overall yield after final recrystallization.",10.1002/ejoc.201402886,2014-09-08,0.6580880081752075
Organic Letters,Highly Stereoselective and Efficient Total Synthesis of (+)-Laurencin,A highly stereoselective and efficient asymmetric total synthesis of (+)-laurencin (1) has been accomplished from the known oxazolidinone 5 in 15 steps. The route features an efficient internal alkylation to form oxocene 3 from 4 and a novel use of acetonitrile anion as a two-carbon acetaldehyde equivalent for direct synthesis of ketone 2 from alpha-alkoxy amide 3.,10.1021/ol047877d,2004-12-10,0.6580831698079329
Journal of the American Chemical Society,Total Synthesis of the <i>Akuammiline</i> Alkaloid (±)-Vincorine,"The first total synthesis of the akuammiline alkaloid (+/-)-vincorine (6) has been accomplished in about 1% overall yield in 31 steps. A concise assembly of the core 1,2-disubstituted 1,2,3,4-tetrahydro-4a,9a-iminoethanocarbazole (1), a distinctive feature of akuammiline and strychnos alkaloids, was developed via a three-step one-pot cascade reaction consisting of copper-catalyzed intramolecular cyclopropanation, ring-opening, and ring closure. The construction of the last seven-membered E-ring in a rigid two-ring moiety (31, 45 to 47) through Heck coupling, Michael addition, pi-allyl/Heck or pi-allyl/Stille coupling failed, leading us to seek an alternative method. After successful addition of an acetate side chain on C15 of the cyclohexenyl ring (D-ring) in Boc-protected 35b by a Johnson-Claisen rearrangement and multistep modification of the functionality in the rearrangement product 33a, the E-ring formation was then realized for providing pentacyclic lactam 32 through intramolecular condensation of the acid group on the D-ring and the amine group on the C-ring with Mukaiyama's reagent. An E-ethylidenyl group on the E-ring was stereoselectively added to afford lactam 56a through a two-step reaction of 32 consisting of aldol addition with acetaldehyde and cis-elimination of the resulting hydroxyl group. Final elaboration of 56a, including opening of the seven-membered E-ring, selective reduction of the alpha,beta-unsaturated ester, and reclosure of the seven-membered E-ring completed the total synthesis of 6.",10.1021/ja901219v,2009-03-27,0.6580541560784278
Synlett,Photochemical Synthesis of N-Substituted 3-Hydroxy-2-pyrrolidinones,A new three-step synthesis to 3-hydroxy-2-pyrrolidi­nones starting from β-amino acids has been developed. The key step is a novel reductive photocyclization.,10.1055/s-2005-865229,2005-01-01,0.6580382166041963
Organic Letters,Total Synthesis of the Photoprotecting Dipyrrolobenzoquinone (+)-Terreusinone,"The first synthesis of (+)-terreusinone 1, a dipyrrolobenzoquinone with a potent UV-A protecting capability, is described. Key transformations include a one-pot Larock indolization-Sonogashira coupling reaction and the hydroamination of an unsubstituted ortho-alkynylaniline catalyzed by a cationic gold(I) complex. The synthesis proceeds in eight steps from commercially available starting materials, confirming the structure and absolute configuration of the natural product.",10.1021/ol2027398,2011-11-14,0.6580095844590513
Organic Letters,Enantioselective Synthesis of a Chiral <i>C</i><sub>3</sub>-Symmetric Bridgehead Amine,An efficient enantioselective synthesis of the above C(3)-symmetric chiral quinuclidine starting with N-tert-butoxycarbonyl-4-pyridone has been developed.,10.1021/ol100426m,2010-03-23,0.6579909740883454
Journal of Organic Chemistry,A Photoreactive Analogue of the Immunosuppressant FTY720,"An azido group was incorporated into the immunomodulatory agent FTY720, accomplishing the first synthesis of a photoactivatable analogue of this ligand (2) in 9 steps from 2-(4-hydroxyphenyl)ethanol and in 34% overall yield. The key steps are formation of a primary amine at a quaternary center of aniline derivative 13 followed by selective diazotization of the arylamine.",10.1021/jo0526237,2006-02-09,0.6579673887371588
Synlett,Formal Total Synthesis of Ovalcin by Carbohydrate Approach,A formal total synthesis of ovalcin is described herein starting from readily available sugar ribose with selective zinc-mediated ring-opening reaction and Grubbs olefin metathesis as the key steps.,10.1055/s-2007-970767,2007-03-26,0.6579430661246507
Journal of the American Chemical Society,Symmetry-Driven Total Synthesis of Myrioneurinol,"We report a total synthesis of the Myrioneuron alkaloid myrioneurinol enabled by the recognition of hidden symmetry within its polycyclic structure. Our approach traces myrioneurinol’s complex framework back to a symmetrical diketone precursor, a double reductive amination of which forges its central piperidine unit. By employing an inexpensive chiral amine in this key desymmetrizing event, four stereocenters of the natural product including the core quaternary stereocenter are set in an absolute sense, providing the first asymmetric entry to this target. Other noteworthy strategic maneuvers include utilizing a bicyclic alkene as a latent cis -1,3-bis(hydroxymethyl) synthon and a topologically controlled alkene hydrogenation. Overall, our synthesis proceeds in 18 steps and ∼1% yield from commercial materials.",10.1021/jacs.2c04487,2022-06-14,0.6579003447991331
Journal of Organic Chemistry,High-Yield Total Synthesis of (−)-Strictinin through Intramolecular Coupling of Gallates,"This paper describes a total synthesis of (-)-strictinin, an ellagitannin that is 1-O-galloyl-4,6-O-(S)-hexahydroxydiphenoyl (HHDP)-β-D-glucose. In the study, total efficiency of the synthesis was improved to produce a 78% overall yield in 13 steps from D-glucose. In the synthesis, formation of the 4,6-(S)-HHDP bridge including the 11-membered bislactone ring was a key step, in which intramolecular aryl-aryl coupling was adopted. The coupling was oxidatively induced by CuCl2-n-BuNH2 with perfect control of the axial chirality, and the reaction conditions of this coupling were optimized thoroughly to achieve the quantitative formation of the bridge.",10.1021/jo4003135,2013-04-08,0.6578826208559972
Journal of Organic Chemistry,Approach Toward the Total Synthesis of Griseoviridin: Formation of Thioethynyl and Thiovinyl Ether-Containing Nine-Membered Lactones through a Thioalkynylation−Macrolactonization−Hydrostannylation Sequence,"Synthesis of the lactone core 17 of 8-epi-griseoviridin is reported. Thioethynyl derivative 11 was easily prepared via an anionic coupling reaction between acetylenic compound 9 and sulfone 10. After desilylation of 11, saponification of the resulting hydroxy ester 12 followed by a Mitsunobu macrolactonization furnished the unusual triple-bond-containing nine-membered lactone 13 in 50% yield for the last two steps (39% after recrystallization). Stannylation under Magriotis conditions led to the pure regio- and stereocontrolled vinyltin 14 (80% yield). After a Sn/I exchange, palladium-catalyzed carbonylation delivered either the ester lactone 16 in 67% yield or the propargyl amide 17 in 65% yield. Synthesis of propargyl amide 17 of the lactone core of 8-epi-griseoviridin was achieved in 11.9% overall yield from commercial L-cystin dimethyl ester (nine steps).",10.1021/jo0103120,2002-05-31,0.6578818396156214
Organic Process Research & Development,"Process Development for ABT-472, a Benzimidazole PARP Inhibitor","A nine-step convergent process was developed for the synthesis of ABT-472, a benzimidazole PARP inhibitor. The identity and origin of several impurities were determined, and the process was modified to reduce or eliminate these impurities. A number of safety and control issues were investigated. The original synthesis was shortened to 9 steps and streamlined while maintaining a convergent strategy. A stable salt was selected, and control of the API solid form was established. The process was successfully scaled up to provide 8.5 kg of final product of >99% purity in 33% yield over 9 steps.",10.1021/op7000194,2007-05-15,0.657880102960204
Organic Letters,An Approach to a Bislactone Skeleton: A Scalable Total Synthesis of (±)-Penifulvin A,"An efficient and scalable total synthesis of the architecturally challenging sesquiterpenoid (±)-penifulvin A has been accomplished via a 12-step sequence with an overall yield of 16%. For the construction of this structurally complex tetracyclic molecule, the key steps used included 1,4-conjugate addition, a Pd(0) catalyzed cross-coupling reaction between an enol phosphate and trimethyl aluminum, Claisen rearrangement using the Johnson orthoester protocol, Ti(III)-mediated reductive epoxide opening-cyclization, Lewis acid catalyzed epoxy-aldehyde rearrangement, and finally a substrate controlled oxidative cascade lactonization process.",10.1021/ol500768w,2014-05-07,0.6578586723092451
Journal of Organic Chemistry,"Total Synthesis of Chlorocyclinone A, a PPAR-γ Antagonist","The first total synthesis of chlorocyclinone A (1) is regioselectively completed in 28 steps. The key steps are Pd-catalyzed methoxycarbonylation, unprecedented Hauser annulation, Krohn photo-oxidation, and regioselective gem-dichlorination.",10.1021/jo301712b,2012-10-18,0.6578576931731169
Journal of the American Chemical Society,Synthesis of 3-Carbomethoxy-3-methylcyclo-pentanone,"Ruzicka has reported the preparation of 3-carbethoxy-3-methylcyclopentanone (I) through severa1 steps from ethyl levulinate. In the present investigation, a shorter synthesis of the corresponding methyl ester (II) was achieved from the adduct of butadiene with methyl methacrylate by the following route.",10.1021/ja01177a519,1949-09-01,0.6578472088103708
Tetrahedron,"A new practical asymmetric synthesis of C2-symmetrical 1,1′-ferrocenyl diols via CBS-reduction",,10.1016/0040-4039(95)02098-5,1996-01-01,0.6578231671519817
Journal of Organic Chemistry,Multicomponent Synthesis of the SARS-CoV-2 Main Protease Inhibitor Nirmatrelvir,"In the wake of the Covid-19 pandemic, it has become clear that global access to efficacious antiviral drugs will be critical to combat future outbreaks of SARS-CoV-2 or related viruses. The orally available SARS-CoV-2 main protease inhibitor nirmatrelvir has proven an effective treatment option for Covid-19, especially in compromised patients. We report a new synthesis of nirmatrelvir featuring a highly enantioselective biocatalytic desymmetrization (>99% ee) and a highly diastereoselective multicomponent reaction (>25:1 dr) as the key steps. Our route avoids the use of transition metals and peptide coupling reagents, resulting in an overall highly efficient and atom-economic process.",10.1021/acs.joc.3c01274,2023-08-22,0.6578114647491998
Organic Process Research & Development,"Synthesis of Tetracyclic Heterocompounds as Selective Estrogen Receptor Modulators. Part 2. Process Improvement for Scale-Up Of 2,5,8-Substituted 11,12-Dihydro-5<i>H</i>-6,13-dioxabenzo[3,4]cyclohepta-[1,2-<i>a</i>]naphthalene Derivatives","An improved, reproducible nonchromatographic process for scale-up synthesis of 2,5,8-substituted 11,12-dihydro-5 H -6,13-dioxabenzo[3,4]cyclohepta[1,2- a ]naphthalene derivatives as selective estrogen receptor modulators (SERMs) is described. The titled compounds were prepared in 9−21% overall yield with high chemical purity (>97%) after nine consecutive synthetic steps.",10.1021/op700061x,2007-06-21,0.6577289085115668
Tetrahedron,An organocatalytic route to the synthesis of lactone moiety of compactin and mevinolin,,10.1016/j.tetlet.2010.08.093,2010-09-07,0.6576934612767801
Organic Letters,Asymmetric Total Synthesis of Rumphellclovane E,"The first asymmetric total synthesis of rumphellclovane E, a clovane-type sesquiterpenoid, has been accomplished in eight steps from commercially available ( R )-carvone. Key elements of the synthesis include Rh-catalyzed cyclopropanation, iron-catalyzed intramolecular reductive aldol reaction, and SmI 2 -mediated chemo- and diastereoselective reduction of the cyclopentanone.",10.1021/acs.orglett.0c03748,2020-12-24,0.6576669956403998
Tetrahedron,Synthesis and reactivity of benzoxa(thia)zol-2-thiones: new route to 2-alkylthiobenzoxa(thia)zoles,,10.1016/s0040-4039(00)00758-9,2000-07-01,0.6576649873284078
Journal of Organic Chemistry,Synthesis of Psychrophilin E,"The first total synthesis of psychrophilin E, a potent antiproliferative cyclic tripeptide isolated from Aspergillus versicolor ZLN-60, is reported herein. Key features of the synthesis include the installation of an amide bond between the indole-nitrogen of tryptophan and an anthranilic acid residue, and a high yielding macrolactamization of the linear tripeptide to the desired macrocycle.",10.1021/acs.joc.6b01369,2016-07-21,0.6576425577000385
Organic Letters,Enantioselective Preparation of Ring-Fused 1-Fluorocyclopropane-1-carboxylate Derivatives: En Route to mGluR 2 Receptor Agonist MGS0028,"[reaction: see text] An approach to the densely functionalized fluorocyclopropane 14, a key framework toward the synthesis of mGluR 2 receptor agonist MGS0028 (1) is reported. The Trost AAA reaction enantioselectively introduced the key allylic stereogenic center and the alpha-fluoroester moiety. Stereoselective epoxidation followed by intramolecular epoxide ring opening efficiently constructed the 1-fluorocyclopropane-1-carboxylate matrix. This route can potentially be a general methodology for a concise, highly enantio- and stereoselective synthesis of 1-fluorocyclopropane-1-carboxylate derivatives.",10.1021/ol0484512,2004-09-11,0.6576294863653339
Tetrahedron,A route to dihydrofuran fused naphthoquinones via gold-catalyzed oxyarylation of alkenes,,10.1016/j.tetlet.2025.155755,2025-07-19,0.6576286043873713
Organic Letters,"First Total Synthesis of Vialinin A, a Novel and Extremely Potent Inhibitor of TNF-α Production","Vialinin A, a powerful inhibitor (IC50 90 pM) of TNF-alpha production, was synthesized from sesamol in 11 steps with 28% overall yield. The key reactions include a double Suzuki coupling of electron-rich aryl triflate with phenylboronic acid and an oxidative deprotection of bis-MOM ether. In addition, the related synthetic studies also suggest the necessity for structural revision of ganbajunin C, a positional isomer of vialinin A.",10.1021/ol701590b,2007-09-12,0.6576265740218457
Organic Process Research & Development,"A Practical and Economical High-Yielding, Six-Step Sequence Synthesis of a Flavone: Application to the Multigram-Scale Synthesis of Ladanein","Herein we report a short and economic synthesis of the antiviral flavonoid lead ladanein ( 1 ). Ladanein is obtained from 2,6-dimethoxyquinone ( 11 ) in six steps with 51% overall yield. After a high-yielding reductive acetylation and Fries rearrangement, the flavone skeleton is built by means of a Baker–Venkataraman rearrangement. Throughout the synthetic pathway no chromatographic columns were used, and the reaction products were isolated and purified by optimized work-up and crystallization processes. This new process has been tested on a multigram-scale with an improved overall yield from 16 to 51% through six steps, and three chromatographic purifications used in the earlier synthesis were eliminated.",10.1021/op4003642,2014-04-10,0.6576258612404294
Green Chemistry,Synthesis of polymerizable vinyltriazoles: development of an optimized one-pot strategy starting from 4-bromobutyne,"The development and implementation of a safe and scalable process for the preparation of isomeric vinyl-1,2,3-triazoles under mild conditions are described. Key aspects of the route reside in a one-pot click-elimination procedure in aqueous media leading to simple work-up and purification steps with increased overall yields.",10.1039/c3gc37066f,2013-01-01,0.6575986876732365
Synlett,A Concise Synthesis of (-)-Deoxoprosopinine,A simple and highly efficient approach to (-)-deoxo­prosopinine from racemic epoxide as a starting material is described employing a Jacobsen’s hydrolytic kinetic resolution (HKR) and Sharpless asymmetric dihydroxylation (AD) as key steps.,10.1055/s-2007-991056,2007-09-25,0.6575749646267793
Tetrahedron,A new route to 4-oxygenated isoxazolines. Application to the synthesis of 2-deoxy-2-aminobutose derivatives,,10.1016/s0040-4039(00)72711-0,1989-01-01,0.6575503761418963
Journal of Organic Chemistry,"Synthesis of 2-Substituted (±)-(2<i>R,</i>3<i>R,</i>5<i>R</i>)-Tetrahydrofuran-3,5-dicarboxylic Acid Derivatives","An efficient synthesis of 2-substituted (+/-)-(2R,3R,5R)-tetrahydrofuran-3,5-dicarboxylic acid derivatives has been developed. Starting from 5-norborne-2-ol, the key intermediate (+/-)-methyl 5,6-exo,exo-(isopropylidenedioxy)-2-oxabicyclo[2.2.1]heptane-3-exo-carboxylate (15) was synthesized in an efficient six-step sequence. The key transformation is the base-catalyzed methanolysis-rearrangement of (+/-)-6,7-exo,exo-(isopropylidenedioxy)-4-exo-iodo-2-oxabicyclo[3.2.1]octan-3-one (14). Further manipulation of the 3-substituent of (+/-)-methyl 5,6-exo,exo-(isopropylidenedioxy)-2-oxabicyclo[2.2.1]heptane-3-exo-carboxylate (15) followed by deprotection of the diol moiety and ring opening catalyzed by RuCl(3)/NaIO(4) gave the title compounds in good yield.",10.1021/jo001551a,2001-02-16,0.6575370765389397
Synthesis,"Practical Large Scale Synthesis of tert-Butyl (3R,5S)-6-Hydroxy-3,5-O-isopropylidene-3,5-dihydroxyhexanoate: Essential Building Block for HMG-CoA Reductase Inhibitors","All articles of this category Title compound 7 (96% ee, > 98% de) is synthesized enantioselectively in six steps (36% overall yield) from the commercial β -keto ester 8 on a multi-kg scale. asymmetric hydrogenation - syn - β , δ -dihydroxy carboxylate - HMG-CoA reductase inhibitor",10.1055/s-1995-4028,1995-08-01,0.6575297035087853
Organic Process Research & Development,"First Scale-Up: Problems and Resolutions on the Synthesis of WAY-253752, a Novel, Dual-Acting SSRI/5HT<sub>1A</sub> Antagonist","An alternative synthesis of WAY-253752, 1, a novel, dual-acting SSRI/5HT 1A antagonist, was developed and used for the first scale-up. Initially, the target compound was synthesized as part of a diasteromeric mixture separated by chiral preparative HPLC. The new route was designed around intermediates suitable for chiral resolution, and its conditions were successfully determined.",10.1021/op700181n,2007-11-27,0.6575205038878249
Journal of Organic Chemistry,"Concise Asymmetric Synthesis of (+)-CP-99,994 and (+)-L-733,060 via Efficient Construction of Homochiral <i>syn</i>-1,2-Diamines and <i>syn</i>-1,2-Amino Alcohols","An efficient asymmetric synthesis of human NK-1 SP receptor antagonists (+)-CP-99,994 and (+)-L-733,060 was achieved starting from a common chiral intermediate (5). Our route featured the SmI2-induced reductive coupling of N-tert-butanesulfinyl imine (7) with aldehyde (6) as the key step as well as pivotal transformations of the anti-1,2-amino alcohol thus obtained to homochiral syn-1,2-amino alcohol and syn-1,2-diamine for the asymmetric synthesis of 2,3-disubstituted piperidines.",10.1021/jo8002979,2008-03-11,0.6574960868956966
Journal of the American Chemical Society,"A New Strategy for the Enantioselective Synthesis of Carba-Prostacyclin Analogues Based on Organocopper Conjugate Addition to a Bicyclic Azoene and Its Application to the Synthesis of 13,14-Dinor-<i>inter</i>-<i>p</i>-phenylene Carbacyclin","An enantioselective synthesis of E/Z-13,14-dinor-inter-p-phenylene carbacyclin (E/Z-2d) by a new strategy has been realized that holds the prospect of serving as a general route for carba-prostacyclin analogues. The key intermediate in this synthesis is the bicyclic azoene Ts-9, and the key step is the regio- and stereoselective conjugate addition of the chiral arylcopper compound Cu-8d/P-n-Bu3 to the azoene with formation of hydrazone 7d. Enantioselective synthesis of azoene Ts-9 of 95% ee from ketone 4 was accomplished in four and five steps, respectively. Thus, enantioselective deprotonation of bicyclic ketone 4 with chiral base Li-10 and trapping of lithium enolate 11 with ClSiMe3 gave enol ether 12, which was chlorinated with N-chlorosuccinimide (NCS) to afford chloro ketone 13. Alternatively, chloro ketone 13 was also prepared upon chlorination of 11 with NCS. Chloro ketone 13 was converted to chloro hydrazone 14, which upon treatment with a mild base furnished azoene Ts-9. Arylcopper compound 8d of 98% ee was obtained in two steps from alcohol 16, which was prepared by enantioselective reduction of ketone 17 with (-)-diisopinocampheylchloroborane. Carbacyclin derivative E/Z-2d was found to be essentially inactive as an inhibitor of ADP induced human platelet aggregation, having an IC50 of >10 micromol/L.",10.1021/ja0125772,2002-03-29,0.6574711096605153
Organic Process Research & Development,Development of a Synthesis of Kinase Inhibitor AKN028,"The novel tyrosine kinase inhibitor AKN028 has demonstrated promising results in preclinical trials. An expedient protocol for the synthesis of the compound at kilogram scale is described, including an S N Ar reaction with high regioselectivity and a Suzuki coupling. Furthermore, an efficient method for purification and removal of residual palladium is described.",10.1021/acs.oprd.8b00092,2018-09-17,0.6574677855131211
Organic Process Research & Development,An Improved and Impurity-Free Large-Scale Synthesis of Venlafaxine Hydrochloride,An improved and impurity-free synthetic method for large-scale synthesis of venlafaxine hydrochloride was developed using inexpensive reagents. The overall yield obtained from this newly developed process is 55% in a highly pure state with >99.9% purity by HPLC.,10.1021/op200221y,2011-10-20,0.6574620027489778
Organic Letters,"Progress toward a Convergent, Asymmetric Synthesis of Jervine",Progress toward a convergent approach for the enantioselective synthesis of the Veratrum alkaloid jervine is presented. The two requisite fragments were stereoselectively and efficiently fashioned from economical and readily available reagents. Key reactions include (a) a highly diastereoselective Ireland−Claisen rearrangement to establish the necessary cis- relationship between the amine and methyl group on the tetrahydrofuran E-ring; (b) a diastereoselective selenoetherification reaction that enabled the assembly of the D/E oxaspiro[4.5]decene in the needed configuration; and (c) an enzymatic desymmetrization of an abundant achiral diol en route to a key four-carbon building block as a practical alternative to a protected Roche ester reduction.,10.1021/acs.orglett.0c00972,2020-04-14,0.6574555827131398
Tetrahedron,(R)-(+)-β-Veratryl-γ-butyrolactone. A new key-intermediate for the asymmetric synthesis of various lignans,,10.1016/s0040-4039(00)83862-9,1986-01-01,0.6574368175069224
Organic Letters,Total Synthesis of (±)-Cytisine,"[reaction:see text] The nicotine partial agonist cytisine was prepared in five steps featuring an ""in situ"" Stille or Suzuki biaryl pyridine coupling. Differentiation of the pyridyl rings was accomplished via selective benzylation and then reduction of a pyridinium ring. The penultimate diazabicyclo[3.3.1]nonane intermediate was obtained with high diastereoselectivity. A similar sequence has been employed for the synthesis of novel derivative 9-methoxycytisine.",10.1021/ol0067538,2000-12-01,0.6574300200031635
Journal of Organic Chemistry,Synthesis and Properties of a New Member of the Calixnaphthalene Family:  A<i>C</i><sub>2</sub>-Symmetrical<i>endo</i>-Calix[4]naphthalene,"The synthesis of a new endo-calix[4]naphthalene is described. The reaction sequence involves the cyclocondensation of a key bisnaphthylmethane intermediate (8) with formaldehyde. This key intermediate (8) is formed using a modified Suzuki-Miyaura Pd-catalyzed cross-coupling reaction between bromomethylnaphthyl (6) and naphthylboronic acid (7), both of which can be derived from 2-hydroxynaphthoic acid.",10.1021/jo026045v,2002-08-29,0.6574229583726663
Organic Letters,Synthetic Study toward Total Synthesis of (±)-Germine: Synthesis of (±)-4-Methylenegermine,The total synthesis of 4-methylenegermine is described.,10.1021/acs.orglett.7b02434,2017-09-06,0.6574215081544871
Organic Letters,Synthesis of Paclitaxel. 1. Synthesis of the ABC Ring of Paclitaxel by SmI<sub>2</sub>-Mediated Cyclization,"A convergent synthesis of the ABC ring of antitumor natural product paclitaxel (Taxol) is described. SmI2-mediated reductive cyclization of an allylic benzoate possessing an aldehyde function, synthesized from tri-O-acetyl-d-glucal and 1,3-cyclohexanedione, smoothly afforded the highly strained 6-8-6 tricarbocyclic structure in 66% yield.",10.1021/acs.orglett.5b01173,2015-05-26,0.6573902080892359
Synlett,"One-Step Synthesis of β, meso-Unsubstituted Dipyrromethane","All articles of this category A novel one-step synthetic route to β, meso-unsubstituted dipyrromethane was established, with a yield of 40%, avoiding the traditional route involving thiophosgene. dipyrromethane - one-pot synthesis",10.1055/s-1995-5244,1995-12-01,0.6573846237181172
European Journal of Organic Chemistry,Total Synthesis of (−)‐Magnoshinin and (+)‐Merrilliaquinone: Application of a Late‐Stage Oxidative Functionalization Protocol,"Abstract A unified approach for the first enantioselective total synthesis of magnoshinin and merrilliaquinone is reported. The key feature of the synthesis is the DDQ assisted chemoselective late‐stage oxidative functionalization of the polyoxygenated chiral tetralin core accessed by utilizing the relayed asymmetric induction strategy. Then, the follow‐up of chemoselective redox chemistry facilitates the synthesis of (−)‐magnoshinin (28.2 % overall yield) and (+)‐merrilliaquinone (20.6 % overall yield) along the shortest route, starting from the known 3‐(2,4,5‐trimethoxyphenyl)propanoic acid.",10.1002/ejoc.202101452,2022-01-25,0.6573757270326145
Synthesis,"Total Syntheses of (±)-(Z)- and (±)-(E)-9-(Bromomethylene)-1,5,5-trimethylspiro[5.5]undeca-1,7-dien-3-one and (±)-Majusculone","A new total synthesis of the chamigrene sesquiterpenoids (Z)-9-(bromomethylene)-1,5,5-trimethylspiro[5.5]undeca-1,7-diene-3-one and its 15-E-epimer has been accomplished in 13 steps. In our sequence, a Diels-Alder reaction and subsequent reductive alkylation of the resulting adduct was utilized as the key strategy to create the A-ring and the quaternary spirocenter with the suitable functionalities for accessing the B-ring. Additionally, from the advanced intermediate, a total synthesis of (±)-majusculone, a nor-chamigrene natural product, was also readily achieved in two steps.",10.1055/s-0030-1258412,2011-01-18,0.6572988911799951
Tetrahedron,A new synthetic route to oligoribonucleotides based on CpRu-catalyzed deallylation,,10.1016/j.tetlet.2007.08.032,2007-08-15,0.657290025921337
Synthesis,Synthesis of the CDK-Inhibitor Paullone by Cyclization of a Deprotonated α-Aminonitrile,Cyclization of a deprotonated N-monosubstituted α-aminonitrile obtained by Strecker reaction of a protected 2-amino­benzaldehyde with ethyl 2-aminocinnamate serves as the key step in a short synthesis of the tetracyclic ε-lactam paullone.,10.1055/s-0028-1083250,2008-12-01,0.6572890101702797
Tetrahedron,"Development of a scalable synthetic route towards a 2,2,6-trisubstituted chiral morpholine via stereoselective hydroalkoxylation",,10.1016/j.tetlet.2018.03.042,2018-03-19,0.6572520883668279
Organic Process Research & Development,Stereoselective Synthesis of a Tubulysin Core for Antibody–Drug Conjugate Studies,"An expeditious synthesis of an advanced tripeptide intermediate en route to a tubulysin antibody–drug conjugate payload is described. The efficient formation of an N -propyl tertiary amide required tailoring the amine component to reduce steric demand. Additionally, double activation of the carboxylate was required via an aluminum–Lewis acid coupled activated ester strategy to enable the formation of the highly congested amide bond with superior retention of stereochemical integrity. Other permutations of reactant structure and reagents met with failure. The realization of this key direct bond construction enabled a convergent solution-phase synthesis of the unnatural tubulysin tripeptide in a highly convergent manner from three simple building blocks in eight steps and 22.4% overall yield utilizing only a single silica gel chromatographic purification.",10.1021/acs.oprd.2c00010,2022-02-28,0.6572451947635546
Journal of Organic Chemistry,An Enantioselective Strategy for the Synthesis of (<i>S</i>)-Tylophorine via One-Pot Intramolecular Schmidt/Bischler–Napieralski/Imine-Reduction Cascade Sequence,"A novel enantioselective strategy for the total synthesis of (S)-tylophorine was developed in an overall yield of 48% with more than 99% ee from readily avaliable azido acid and phenanthryl alcohol. This route features an Evans stereoselective alkylation and an unprecedented one-pot intramolecular Schmidt/Bischler-Napieralski/imine-reduction cascade sequence, in which three new bonds and two rings formed in 84% yield. The intramolecular Schmidt rearrangement of the azido aldehyde was proved to be racemization-free.",10.1021/jo302725q,2013-02-01,0.6572401181125577
Journal of Organic Chemistry,Asymmetric Synthesis of the Core Structure of Leucosceptroids A–D,"The asymmetric synthesis of the core structure of leucosceptroids A-D has been achieved. The key steps of the synthesis includes the formation of the cis-2,5-disubstituted THF ring by TPAP catalytic oxidative cyclization followed by a highly diastereoselective intramolecular Diels-Alder reaction to fashion the fused tricyclic hydrindane ring system.",10.1021/jo200899v,2011-06-28,0.6572398537977455
Organic Letters,Synthetic Strategy toward the C44–C65 Fragment of Mirabalin,"A convergent and flexible stereoselective synthesis of one isomer of the C44-C65 fragment of mirabalin is described. The key steps include organocatalytic aldolization, ruthenium-catalyzed asymmetric hydrogenation, amide formation, Marshall stereoselective allenylation, and the Nozaki-Hiyama-Kishi reaction.",10.1021/ol500720j,2014-04-11,0.6572377045569259
Tetrahedron,Cyclization of a chiral oxazolidine as a key-step for the synthesis of functionalized piperidines,,10.1016/0040-4039(96)00767-8,1996-06-01,0.6572371144696314
Synthesis,Asymmetric Total Synthesis of (+)-2-epi-Deoxoprosopinine,"All articles of this category The asymmetric synthesis of (+)-2- epi -deoxoprosopinine [( S,S , R )- 5 ] in eleven steps and with excellent diastereomeric and enantiomeric purity (de, ee ≥96%) is described. As key steps, the 1,2-addition of a dodecyl nucleophile to an aldehyde-SAMP hydrazone and the α -alkylation of 2,2-dimethyl-1,3-dioxan-5-one SAMP hydrazone are employed to generate two of the three stereogenic centers. Creation of the third stereogenic center was achieved in a domino deprotection/cyclisation/reduction sequence. asymmetric synthesis - deoxoprosopinine - SAMP/RAMP hydrazone method - natural products - piperidine alkaloids",10.1055/s-2000-8733,2000-01-01,0.6572271348559416
Tetrahedron,A new route to the synthesis of 3-methylenecoumarins-via Lewis acid catalyzed rearrangement of methyl α-aryloxymethylacrylates,,10.1016/0040-4039(84)80025-8,1984-01-01,0.6572244104566746
Organic Letters,An Enantioselective Total Synthesis of (+)-Geissoschizine,"[formula: see text] A concise asymmetric synthesis of the indole alkaloid (+)-geissoschizine (1) has been completed. The synthesis features the highly diastereoselective vinylogous Mannich reaction of 3 with 4 to give 5, which is elaborated into the key tetracyclic intermediate 7 in two steps. Following the stereoselective introduction of the ethylidene moiety to give 9, reduction of the lactam and radical decarboxylation via an acyl selenide gave 12, which was converted into (+)-geissoschizine by formylation. The synthesis requires only 11 chemical operations and proceeds in an overall yield of 17%.",10.1021/ol990554a,1999-05-17,0.6572053787411101
Journal of Organic Chemistry,Enantioselective Total Synthesis of Potent 9β-11-Hydroxyhexahydrocannabinol,"The first total synthesis of potent cannabinoid, 9β-11-hydroxyhexahydrocannabinol, is achieved through a proline-catalyzed inverse-electron-demand Diels-Alder reaction. Using this asymmetric catalysis, the cyclohexane ring is constructed with two chiral centers as a single diastereomer with 97% ee. The creation of the third chiral center and benzopyran ring is demonstrated with the elegant synthetic strategies. This mild and efficient synthetic methodology provides a new route for the asymmetric synthesis of the other potent hexahydrocannabinols.",10.1021/acs.joc.9b02962,2019-12-13,0.6572037155698002
Angewandte Chemie International Edition,Total Synthesis of the <i>Isodon</i> Diterpene Sculponeatin N,"The total synthesis of sculponeatin N, a bioactive polycyclic diterpene isolated from Isodon sculponeatus, is reported. Key features of the synthesis include diastereoselective Nazarov and ring-closing metathesis reactions, and a highly efficient formation of the bicyclo[3.2.1]octane ring system by a reductive radical cyclization.",10.1002/anie.201310060,2014-02-12,0.6571830069417657
Synthesis,Enantioselective Syntheses of Yohimbine Alkaloids: Proving Grounds for New Catalytic Transformations,"Abstract The total synthesis of bioactive alkaloids is an enduring challenge and an indication of the state of the art of chemical synthesis. With the explosion of catalytic asymmetric methods over the past three decades, these compelling targets have been fertile proving grounds for enantioselective bond forming transformations. These activities are summarized herein both to highlight the power and versatility of these methods and to instill future inspiration for new syntheses of these privileged natural products. 1 Introduction 2 Monoterpenoid Indole Alkaloids 2.1 Corynanthe-Type MIAs 3 Biosynthesis 4 Biological Activity 5 Scope 6 Strategies in Yohimbine Alkaloid Synthesis 6.1 Momose’s Formal Synthesis of (+)-Yohimbine 6.2 Jacobsen’s Synthesis of (+)-Yohimbine 6.3 Hiemstra’s Synthesis of (+)-Yohimbine 6.4 Qin’s Synthesis of (–)-Yohimbine 6.5 Tan’s Synthesis of (+)-Rauwolscine 6.6 Jacobsen’s Synthesis of (+)-Reserpine 6.7 Chen’s Synthesis of (+)-Reserpine 6.8 Riva’s Synthesis of (–)-Alloyohimbane 6.9 Katsuki’s Synthesis of (–)-Alloyohimbane 6.10 Ghosh’s Synthesis of (–)-Yohimbane and (–)-Alloyohimbane 6.11 Hong’s Synthesis of (–)-Yohimbane 6.12 Gellman’s Synthesis of (–)-Yohimbane 6.13 Scheidt’s Synthesis of (–)-Rauwolscine and (–)-Alloyohimbane 7 Conclusion",10.1055/a-1684-2942,2021-11-02,0.6571763261730766
Organic Process Research & Development,Approaches to a Scaleable Synthesis of CH8757:  A Potent Inhibitor of Matrix Metalloproteinases,"The synthesis of the matrix metalloproteinase (MMP) inhibitor CH8757 is described. The discovery route has been modified to incorporate a three-stage one-pot sequence using α,α,α-trifluorotoluene as solvent. The formation of the hydroxamic acid using oxalyl chloride is catalysed by DBU, thus avoiding the use of DMF, which may form the highly toxic byproduct, dimethylcarbamoyl chloride.",10.1021/op049954q,2004-04-10,0.6571533175785469
Journal of Organic Chemistry,Synthesis of a Naphthyridone p38 MAP Kinase Inhibitor,"Compound 1 is a p38 MAP kinase inhibitor potentially useful for the treatment of rheumatoid arthritis and psoriasis. A novel six-step synthesis suitable for large-scale preparation was developed in support of a drug development program at Merck Research Laboratories. The key steps include a tandem Heck-lactamization, N-oxidation, and a highly chemoselective Grignard addition of 4-(N-tert-butylpiperidinyl)magnesium chloride to a naphthyridone N-oxide. The N-oxide exerted complete chemoselectivity via chelation in directing the Grignard addition to the alpha position as opposed to 1,4-addition on the ene-lactam. The dihydropyridyl adduct was in situ aromatized with isobutylchloroformate followed by heating in pyridine. Syntheses of Grignard precursor, N-tert-butyl-4-chloro-piperidine, were accomplished via transamination with a quaternary ammonium piperidone or via addition of methylmagnesium chloride to an iminium ion. Utilizing this chemistry, multi-kilogram preparation of compound 1 was successfully demonstrated.",10.1021/jo061618f,2006-10-01,0.6571528085492625
Synthesis,Total Synthesis of Thiocladospolide A and Its C2-Epimer,"Abstract The first total synthesis of the recently isolated natural product thiocladospolide A, along with its C2-epimer, is achieved in nine straightforward linear steps and 12% overall yield. The key feature of the synthesis is the construction of the macrocyclic ring via a late-stage ring-closing metathesis reaction followed by alkene reduction.",10.1055/a-1652-3714,2021-09-23,0.6571407678137515
Organic Letters,Enantioselective Total Synthesis of Mollebenzylanol A,"Mollebenzylanol A is a tyrosine phosphatase 1B inhibitor isolated from the leaves of Rhododendron molle in 2018 that has a highly functionalized structure. The first enantioselective total synthesis of mollebenzylanol A was achieved in 13 steps from a known chiral starting material. An efficient and practical synthetic scheme was disclosed in a stereocontrolled manner, including stereo/regioselective epoxidation, Eschenmoser–Claisen rearrangement, and stereocontrolled dihydroxylation.",10.1021/acs.orglett.0c02811,2020-09-14,0.6571325558038668
Organic Letters,Synthesis of a Precursor to Sacubitril Using Enabling Technologies,"An efficient preparation of a precursor to the neprilysin inhibitor sacubitril is described. The convergent synthesis features a diastereoselective Reformatsky-type carbethoxyallylation and a rhodium-catalyzed stereoselective hydrogenation for installation of the two key stereocenters. Moreover, by integrating machine-assisted methods with batch processes, this procedure allows a safe and rapid production of the key intermediates which are promptly transformed to the target molecule (3·HCl) over 7 steps in 54% overall yield.",10.1021/acs.orglett.5b02806,2015-10-28,0.657112519709045
Synthesis,"Stereoselective Synthesis of 4-Amino-3-hydroxy-4,5,6,6a-tetrahydro-3a<i>H</i>-cyclopenta[<i>d</i>]isoxazole-4-carboxylic Acid, a Conformationally Constrained Analogue of Aspartic Acid","An alternative synthesis of 4-amino-3-hydroxy-4,5,6,6a-tetrahydro-3aH-cyclopenta[d]isoxazole-4-carboxylic acid, a conformationally constrained analogue of aspartic acid, is described. The synthetic strategy is based on a regioselective 1,3-dipolar cycloaddition to give the cyclopenta[d]isoxazoline framework; subsequent condensation of this 4-oxocyclopenta[d]isoxazoline with 4-methoxybenzylamine gives a 4-imino derivative, which undergoes a highly stereoselective nucleophilic attack by the cyanide ion. This gives a 4-(methoxybenzylamino)-4-cyano derivative, which is oxidized to the corresponding 4-amino-4-cyano derivative, which itself is transformed into the target 4-carboxylic acid. This amino acid is obtained in 27% overall yield in five steps, whereas the previously described synthetic strategy gave the target derivative in only 0.5% overall yield over 15 steps.",10.1055/s-2007-983750,2007-07-03,0.6570605025680135
Organic Process Research & Development,An Improved Synthesis of Nomegestrol Acetate,"Oral contraceptives (OCs) are synthetic steroids, or progestins, which are structurally related to testosterone or to progesterone. Many progestins have been synthesized and approved for OCs, hormonal replacement therapy (HRT), or the treatment of some gynecological disorders. Nomegestrol acetate (NOMAc) is a newly approved OC and has gained rapid acceptance in many countries for OC or HRT. The synthesis of NOMAc remains challenging and costly. We have developed a novel and improved procedure for the synthesis of NOMAc with a total of 11 steps and an overall good yield without the use of hazardous reagents.",10.1021/op4003533,2014-02-04,0.6570548239343763
Journal of Organic Chemistry,Enantioselective Synthesis of the C<sub>10</sub>–C<sub>20</sub> Fragment of Fusicoccin A,"A synthesis of the fully protected C-ring fragment of the tricyclic diterpene fusicoccin A is reported. The desired cyclopentenyl halides 5a,b are obtained in a total of nine steps. Key transformations of the synthesis sequence are a nonconventional Cr-catalyzed allylic oxidation of a protected intermediate cylcopentenone, a diastereoselective addition of a propenyl Grignard/CeCl(3) reagent to the unmasked cyclopentenone, and an asymmetric hydroboration of the isopropenyl substituent. The protected and suitably functionalized C-ring fragment paves the way to explore further the total synthesis of fusicoccin A.",10.1021/jo201020v,2011-07-14,0.657023170288172
Journal of Organic Chemistry,"Total Synthesis of Hyacinthacine A<sub>1</sub>, a Glycosidase Inhibitor","A practical and enantioselective total synthesis of hyacinthacine A1 is achieved involving syn allylic epoxide opening with retention using Pd catalysis and ""domino"" hydrogenation (five steps in one pot) sequences.",10.1021/jo801377s,2008-09-06,0.6570093841823825
Synlett,A Concise Enantioselective Synthesis of (S)-Preclamol via Asymmetric Catalytic Negishi Cross-Coupling Reaction,"A novel, concise, and efficient enantioselective synthesis of (S)-preclamol (87% ee, 51% total yield) has been developed. The key steps of this synthetic approach included cobalt-catalyzed asymmetric catalytic cross-coupling of α-bromo ester with arylzinc and the reduction of chiral ester to diol with a tertiary carbon atom. Moreover, it was demonstrated that our enantioselective Negishi cross-coupling was a powerful tool to construct stereogenic benzylmethyl center in chiral drugs on a gram scale.",10.1055/s-0037-1611759,2019-03-26,0.656945276000468
Synthesis,"<b>Synthesis of 2′,3′</b> <b> <i>-</i> </b> <b>Dideoxy-2′-difluoromethyl Azanucleosides</b>","Methyl (2S,4S)-N-tert-butoxycarbonyl-4-difluoromethylpyroglutamate (9a) was synthesized from trans-4-hydroxy-l-proline (5). Compound 9a was converted to (5S,3S)-N-benzyloxycarbonyl-5-(tert-butyldimethylsilyloxymethyl-3-difluoromethyl-2-pyrrolidone (15) over 4 steps in 66% yield, which was used as a key intermediate for the synthesis of 2′,3′-dideoxy-2′-difluoromethyl azanucleosides",10.1055/s-2004-815932,2004-01-01,0.6569432311669635
Tetrahedron,"An efficient synthesis of rufinamide, an antiepileptic drug",,10.1016/j.tetlet.2010.04.060,2010-04-19,0.6569404295766501
Organic Process Research & Development,Development of a Robust Process for the Preparation of High-Quality 4-Methylenepiperidine Hydrochloride,"An efficient route for the preparation of 4-methylenepiperidine hydrochloride 1 was designed, and then a process feasible for large-scale production was developed with a total yield of 83.5% at a purity of 99.9%.",10.1021/acs.oprd.7b00350,2017-12-19,0.6569189098515108
European Journal of Organic Chemistry,Convergent Total Synthesis of Murisolin,"Abstract A convergent total synthesis of the mono(tetrahydrofuran) annonaceous acetogenin murisolin, with a longest linear sequence of nine steps, is reported. Assembly of the complete carbon framework by cross metathesis and late‐stage tetrahydrofuran formation on the intact backbone are key elements of the synthesis.",10.1002/ejoc.201000875,2010-09-22,0.6568776596337668
Angewandte Chemie International Edition,"Highly Efficient, Convergent, and Enantioselective Synthesis of Phthioceranic Acid","A new strategy for highly concise, convergent, and enantioselective access to polydeoxypropionates has been developed. ZACA-Pd-catalyzed vinylation was used to prepare smaller deoxypropionate fragments, and then two key sequential Cu-catalyzed stereocontrolled sp(3)-sp(3) cross-coupling reactions allowed convergent assembly of smaller building blocks to build-up long polydeoxypropionate chains with excellent stereoselectivity. We employed this strategy for the synthesis of phthioceranic acid, a key constituent of the cell-wall lipid of Mycobacterium tuberculosis, in just 8 longest linear steps with full stereocontrol.",10.1002/anie.201503818,2015-06-18,0.6568725428325098
Synthesis,A New Synthesis of Flavones,,10.1055/s-1980-29245,1980-01-01,0.6568712960338543
Tetrahedron,A new synthesis of tetracyanotetrathiofulvalene,,10.1016/s0040-4039(00)71856-9,1975-01-01,0.6568712960338543
Synthesis,A New Synthesis of Juglone,,10.1055/s-1977-24517,1977-01-01,0.6568712960338543
Synthesis,A New Synthesis of<i>O</i>-Alkylhydroxylamines,,10.1055/s-1976-24157,1976-01-01,0.6568712960338543
Synthesis,A New Synthesis of Diacylamines,,10.1055/s-1980-28939,1980-01-01,0.6568712960338543
Tetrahedron,A new synthesis of thioketones from hydrazones and disulfur dichloride,,10.1016/s0040-4039(01)95494-2,1979-01-01,0.6568712960338543
Synthesis,A New Synthesis of 4-Hydroxythiazoles,,10.1055/s-1976-24010,1976-01-01,0.6568712960338543
Synthesis,A New Synthesis of 3-Methylcoumarins,,10.1055/s-1975-23849,1975-01-01,0.6568712960338543
Synthesis,"A New Synthesis of Pyridazine 1,2-Dioxides",,10.1055/s-1976-24231,2002-09-12,0.6568712960338543
Tetrahedron,A new synthesis of polyunsaturated allenic carbonyls,,10.1016/0040-4039(94)85321-5,1994-10-01,0.6568712960338543
Tetrahedron,A new synthesis of oxazoles,,10.1016/s0040-4039(00)92606-6,1980-01-01,0.6568712960338543
Tetrahedron,Two new stereochemically complementary oxindole synthesis,,10.1016/s0040-4039(00)87259-7,1982-01-01,0.6568712960338543
Tetrahedron,A new synthesis of armentomycin and its analog,,10.1016/s0040-4039(00)72626-8,1975-01-01,0.6568712960338543
Tetrahedron,The new synthesis of 3-alkoxypyridines,,10.1016/s0040-4039(00)71559-0,1967-01-01,0.6568712960338543
Tetrahedron,A new synthesis of sulfonylnitrenes,,10.1016/s0040-4039(00)75381-0,1968-01-01,0.6568712960338543
Synlett,"1,3-Selenaphospholes: A New Synthesis from 1,2,3-Selenadiazoles and Kinetically Stabilized Phosphaalkynes1",,10.1055/s-1991-21982,1991-01-01,0.6568712960338543
Tetrahedron,"A new synthesis of 1,2,4,6-tetrazepines",,10.1016/s0040-4039(01)90884-6,1963-01-01,0.6568712960338543
Tetrahedron,A new synthesis of anthracyclines,,10.1016/0040-4039(91)80783-3,1991-10-01,0.6568712960338543
Tetrahedron,A new synthesis of truxenone,,10.1016/s0040-4039(96)02473-2,1997-02-01,0.6568712960338543
Tetrahedron,A new synthesis of α-methylene-γ-butyrolactones,,10.1016/s0040-4039(00)75130-6,1964-01-01,0.6568712960338543
Tetrahedron,A New polyamine synthesis.,,10.1016/s0040-4039(00)80276-2,1988-01-01,0.6568712960338543
Tetrahedron,1-Phenylthiocyclopropyltriphenylphosphonium fluoborate: A new synthon for cyclopentanone synthesis,,10.1016/s0040-4039(00)91063-3,1975-01-01,0.6568712960338543
Tetrahedron,Synthesis of new carbocyclic phosphonate analogs of dideoxypurine nucleotides,,10.1016/0040-4039(91)80164-2,1991-10-01,0.6568712960338543
Tetrahedron,A new synthesis of 5-deazaflavins,,10.1016/s0040-4039(00)70548-x,1978-01-01,0.6568712960338543
Tetrahedron,A new synthesis of combretastatins A-4 and AVE-8062A,,10.1016/j.tetlet.2007.07.151,2007-07-31,0.6568712960338543
Tetrahedron,A new flexible synthesis of (D-homo) steroids,,10.1016/j.tetlet.2004.10.102,2004-11-06,0.6568712960338543
Tetrahedron,"New synthesis of 5,6-cyclothymine- and 6-alkyluracil-1-N-β-D-ribosides",,10.1016/s0040-4039(01)86059-7,1979-01-01,0.6568712960338543
Tetrahedron,Synthesis of new glycosylated neutral and cationic porphyrins dimers,,10.1016/s0040-4039(99)02085-7,2000-01-01,0.6568712960338543
Tetrahedron,A new synthesis of β-damascone,,10.1016/s0040-4039(00)92865-x,1980-01-01,0.6568712960338543
Tetrahedron,A new synthesis of t-azoalkanes,,10.1016/s0040-4039(01)82189-4,1974-01-01,0.6568712960338543
Tetrahedron,A new synthesis of azaphenanthrenes,,10.1016/s0040-4039(00)79400-7,1991-07-01,0.6568712960338543
Tetrahedron,"A new synthesis of 1,7-naphthyridine",,10.1016/s0040-4039(01)99700-x,1966-01-01,0.6568712960338543
Tetrahedron,Isatogens V. A new synthesis of Δ4-isoxazolines.,,10.1016/s0040-4039(01)99980-0,1966-01-01,0.6568712960338543
Tetrahedron,A new synthesis of unsymmetrical conjugated diynes,,10.1016/0040-4039(76)80123-2,1976-11-01,0.6568712960338543
Tetrahedron,A new synthesis of corannulene,,10.1016/s0040-4039(97)00267-0,1997-03-01,0.6568712960338543
Tetrahedron,A new synthesis of α-tetralones,,10.1016/s0040-4039(97)00184-6,1997-03-01,0.6568712960338543
Tetrahedron,"The new synthesis of uracil and 1,3-dimethyluracil",,10.1016/s0040-4039(00)78766-1,1976-07-01,0.6568712960338543
Tetrahedron,Synthesis of new dipyridotetraazapentalenes,,10.1016/s0040-4039(97)10311-2,1997-12-01,0.6568712960338543
Tetrahedron,"A new synthesis of 2′,3′-dideoxynucleosides for aids chemotherapy",,10.1016/s0040-4039(00)80265-8,1988-01-01,0.6568712960338543
Tetrahedron,"Synthesis of new chromogenic 2,2′-bithiazoylcalix[4]arenes",,10.1016/s0040-4039(01)01755-5,2001-11-01,0.6568712960338543
Tetrahedron,Synthesis of a new flavonoid-antioxidant,,10.1016/s0040-4039(00)88547-0,1990-01-01,0.6568712960338543
Synthesis,A New Synthesis of (-)-β-Pinene from (-)-α-Pinene,,10.1055/s-1982-29984,1982-01-01,0.6568712960338543
Tetrahedron,"A new synthesis of 1,2,3-thiadiazolo(4,5-d)pyrimidines",,10.1016/s0040-4039(00)93769-9,1976-04-01,0.6568712960338543
Tetrahedron,"A new synthesis of 4,5-dimethoxybenzocyclobutene, 4,5-methylenedioxy-benzocyclobutene and 4-methoxybenzocyclobutene",,10.1016/s0040-4039(00)78134-2,1976-07-01,0.6568712960338543
Tetrahedron,A new synthesis of epidithiapiperazinediones,,10.1016/s0040-4039(00)93053-3,1976-09-01,0.6568712960338543
Tetrahedron,A new synthesis of O-glycosides from totally O-unprotected glycosyl donors,,10.1016/0040-4039(95)00356-h,1995-04-01,0.6568712960338543
Tetrahedron,Synthesis of new chromogenic calix(8)arenes,,10.1016/s0040-4039(00)76662-7,1994-05-01,0.6568712960338543
Tetrahedron,A new synthesis of biotin,,10.1016/s0040-4039(01)81940-7,1981-01-01,0.6568712960338543
Tetrahedron,"1,4 - dialdehyde monoacetals: A new synthesis of dihydrotagetone",,10.1016/s0040-4039(00)78070-1,1976-04-01,0.6568712960338543
Tetrahedron,"A new synthesis of (−)-debromoflustramine B, (+)-ent-debromoflustramine B and (+)-debromoflustramide B",,10.1016/s0040-4039(01)01359-4,2001-09-01,0.6568712960338543
Synthesis,A New Synthesis of α-Carboxy-γ-lactones and α-Methylene-γ-lactones,,10.1055/s-1978-24757,1978-01-01,0.6568712960338543
Synthesis,A New Synthesis of Thione<i>S</i>-Imides,,10.1055/s-1981-29502,1981-01-01,0.6568712960338543
Tetrahedron,"Bischler–Napieralski cyclocondensation in the synthesis of new 11H-pyrimido[4,5-b][1,4]benzodiazepines",,10.1016/j.tetlet.2008.10.026,2008-10-14,0.6568712960338543
Tetrahedron,A new synthesis of pyrroles,,10.1016/s0040-4039(00)70566-1,1962-01-01,0.6568712960338543
Tetrahedron,2-Methylenepenams: A new synthesis,,10.1016/s0040-4039(00)86830-6,1982-01-01,0.6568712960338543
Tetrahedron,A new synthesis of hydroxyphthalides,,10.1016/s0040-4039(00)71525-5,1980-01-01,0.6568712960338543
Tetrahedron,"A new synthesis of ant venom alkaloid : (3S,5R,8S)-3-heptyl-5-methylpyrrolizidine",,10.1016/0040-4039(93)88073-r,1993-07-01,0.6568712960338543
Synthesis,"A New Synthesis of 4<i>H</i>-1,4-Thiazines and Benzothiazines",,10.1055/s-1978-24874,1978-01-01,0.6568712960338543
Tetrahedron,A new synthesis of flavins,,10.1016/s0040-4039(01)85532-5,1976-08-01,0.6568712960338543
Tetrahedron,A new synthesis of sarkomycin,,10.1016/s0040-4039(00)87683-2,1982-01-01,0.6568712960338543
Tetrahedron,A new sulfene synthesis,,10.1016/s0040-4039(00)88704-3,1982-01-01,0.6568712960338543
Tetrahedron,A new synthesis of benzo-c-thiophenes,,10.1016/s0040-4039(00)76277-0,1966-01-01,0.6568712960338543
Tetrahedron,Synthesis of new 2- or 3-deoxy carbapyranoses from furan,,10.1016/s0040-4039(01)01353-3,2001-10-01,0.6568712960338543
Tetrahedron,New synthesis of isoquinoline-3-carboxylates,,10.1016/s0040-4039(99)01588-9,1999-11-01,0.6568712960338543
Tetrahedron,A new synthesis of (±)-sarkomycin from a β-ketophosphonate,,10.1016/s0040-4039(01)80382-8,1989-01-01,0.6568712960338543
Tetrahedron,New synthesis of SKF 89976A,,10.1016/j.tetlet.2006.06.156,2006-07-26,0.6568712960338543
Tetrahedron,A new synthesis of resveratrol,,10.1016/j.tetlet.2015.09.005,2015-09-05,0.6568712960338543
Tetrahedron,"Synthesis of imdazo/1,2-b/-s-triazolo/3′,4′-f/pyridazine a new tricyclic azaheterocycle",,10.1016/s0040-4039(00)75666-8,1966-01-01,0.6568712960338543
Tetrahedron,A new benzazole synthesis,,10.1016/s0040-4039(00)90192-8,1965-01-01,0.6568712960338543
Tetrahedron,A new benzofurazan synthesis,,10.1016/s0040-4039(01)99880-6,1966-01-01,0.6568712960338543
Tetrahedron,A new sulfoximine synthesis,,10.1016/s0040-4039(00)95221-3,1989-01-01,0.6568712960338543
Tetrahedron,A new synthesis of defucogilvocarcin M,,10.1016/s0040-4039(01)93455-0,1989-01-01,0.6568712960338543
Tetrahedron,A new synthesis of indoles,,10.1016/s0040-4039(97)01695-x,1997-10-01,0.6568712960338543
Tetrahedron,New synthesis of thiapyrylium and 1-thianapthaleniium cations,,10.1016/s0040-4039(01)90796-8,1963-01-01,0.6568712960338543
Tetrahedron,A new synthesis of hypoglycin a,,10.1016/s0040-4039(01)90775-0,1963-01-01,0.6568712960338543
Tetrahedron,"Synthesis of the oligosaccharide moieties of musettamycin and marcellomycin, new antitumour antibiotics.",,10.1016/s0040-4039(00)84044-7,1986-01-01,0.6568712960338543
Tetrahedron,A new synthesis of (±)-carbocyclic 2′-deoxyuridines,,10.1016/s0040-4039(00)84090-3,1986-01-01,0.6568712960338543
Tetrahedron,A new synthesis of para-terphenyls,,10.1016/s0040-4039(00)98457-0,1985-01-01,0.6568712960338543
Tetrahedron,Synthesis of new classes of thiocarbonyl ylides and imines,,10.1016/s0040-4039(01)84534-2,1972-01-01,0.6568712960338543
Tetrahedron,A new synthesis of 3-nitroisoxazoles,,10.1016/s0040-4039(01)95677-1,1973-01-01,0.6568712960338543
Tetrahedron,A new pteridine synthesis,,10.1016/s0040-4039(01)94044-4,1972-01-01,0.6568712960338543
Synthesis,A New Synthesis of<i>N</i>-Unsubstituted 2-Vinylaziridines,,10.1055/s-1975-23809,1975-01-01,0.6568712960338543
Tetrahedron,A new synthesis of p-nitrocalix[6]arene,,10.1016/s0040-4039(00)98293-5,1985-01-01,0.6568712960338543
Tetrahedron,A new synthesis of semibullvalenes via photodecarbonylation of norsnoutanones,,10.1016/s0040-4039(98)00890-9,1998-07-01,0.6568712960338543
Tetrahedron,A new synthesis of furans,,10.1016/s0040-4039(01)98971-3,1968-01-01,0.6568712960338543
Tetrahedron,A new synthesis of nitriles,,10.1016/s0040-4039(01)86823-4,1973-01-01,0.6568712960338543
Synthesis,Synthesis of New Condensed 2(3<i>H</i>)-Imidazolinones from Cycloalkanespirohydantoins,,10.1055/s-1985-31191,1985-01-01,0.6568712960338543
Synthesis,A New Synthesis of 5-Vinylpyrimidines,,10.1055/s-1986-31782,1986-01-01,0.6568712960338543
Tetrahedron,"Synthesis of dehydrocineole, a new monoterpene from the acarid mite, (arachnida: acari)",,10.1016/s0040-4039(01)91066-4,1984-01-01,0.6568712960338543
Tetrahedron,A new synthesis of N-benzoyl L-acosamine,,10.1016/s0040-4039(00)99940-4,1984-01-01,0.6568712960338543
Tetrahedron,A new synthesis of phenylvinylselenides,,10.1016/s0040-4039(01)80136-2,1984-01-01,0.6568712960338543
Tetrahedron,A new synthesis of oxanosine and 2′-deoxyoxanosine,,10.1016/s0040-4039(98)01605-0,1998-10-01,0.6568712960338543
Synthesis,A New Synthesis of Monothiodiacylamines,,10.1055/s-1984-31030,1984-01-01,0.6568712960338543
Tetrahedron,"A new synthesis of 3H-1,2-dithiole-3-thiones",,10.1016/s0040-4039(00)79205-7,1993-06-01,0.6568712960338543
Tetrahedron,"Synthesis and characterisation of a new polycyclic phenazine from 1,4-naphthoquinone",,10.1016/j.tetlet.2011.03.006,2011-03-09,0.6568712960338543
Synthesis,A New Synthesis of Cyclobutadienequinones and Benzocyclobutadienequinone,,10.1055/s-1973-22180,2002-03-18,0.6568712960338543
Tetrahedron,New synthesis of 1-triacontanol,,10.1016/s0040-4039(01)91306-1,1984-01-01,0.6568712960338543
Synthesis,"A New Synthesis of 1,3-Diarylisobenzofurans",,10.1055/s-1980-28946,1980-01-01,0.6568712960338543
Synthesis,A New Synthesis of β-Aminoalcohols via<i>O</i>-Silylated Cyanohydrins,,10.1055/s-1981-29409,1981-01-01,0.6568712960338543
Synthesis,A New Synthesis of 2-Alkylcyclopentenones,,10.1055/s-1981-29681,1981-01-01,0.6568712960338543
Synthesis,A New Synthesis of Allylsilanes,,10.1055/s-1981-29528,1981-01-01,0.6568712960338543
Tetrahedron,"Synthesis of new phenylazocalix[n]arenes (n=4, 5)",,10.1016/s0040-4039(00)00259-8,2000-04-01,0.6568712960338543
Tetrahedron,A new synthesis of Rhein,,10.1016/s0040-4039(00)76534-8,1994-01-01,0.6568712960338543
Tetrahedron,New electroreductive synthesis of phthalide alkaloids1),,10.1016/s0040-4039(00)74573-4,1980-01-01,0.6568712960338543
Tetrahedron,"New synthesis of dl-sativene, dl-copacamphene, dl-?-sativenediol and dl-helminthosporal",,10.1016/s0040-4039(01)94654-4,1979-01-01,0.6568712960338543
Tetrahedron,"New Synthesis of dl-sativene, dl-copacamphene, dl--sativenediol and dl-helminthosporal",,10.1016/s0040-4039(01)86211-0,1979-01-01,0.6568712960338543
Tetrahedron,A new synthesis of piperine and isochavicine,,10.1016/s0040-4039(01)87185-9,1979-01-01,0.6568712960338543
Tetrahedron,A new synthesis of a hydroazulenone,,10.1016/s0040-4039(01)86002-0,1979-01-01,0.6568712960338543
Tetrahedron,New synthesis of glycolipid immunostimulants RC-529 and CRX-524,,10.1016/j.tetlet.2006.01.137,2006-02-14,0.6568712960338543
Tetrahedron,New synthesis of glycosides,,10.1016/0040-4039(64)80013-7,1964-01-01,0.6568712960338543
Tetrahedron,A new synthesis of thiophenes,,10.1016/0040-4039(64)83060-4,1964-01-01,0.6568712960338543
Tetrahedron,New synthesis of 3-arylpyrrolines,,10.1016/j.tetlet.2005.12.008,2005-12-22,0.6568712960338543
Tetrahedron,A new synthesis of enaminoketones,,10.1016/s0040-4039(96)02038-2,1996-11-01,0.6568712960338543
Tetrahedron,A new synthesis of cyclotheonamide B via guanidination of ornithine,,10.1016/0040-4039(96)00270-5,1996-03-01,0.6568712960338543
Tetrahedron,"A new synthesis of 2,2′-dialkylchrom-3-enes and flav-3-enes",,10.1016/s0040-4039(01)86344-9,1979-01-01,0.6568712960338543
Tetrahedron,"A new synthesis of d,α-β-santalene and d,α-epi-β-santalene",,10.1016/s0040-4039(01)90947-5,1963-01-01,0.6568712960338543
Tetrahedron,A new synthesis of (±) linalool,,10.1016/s0040-4039(01)89286-8,1966-01-01,0.6568712960338543
Tetrahedron,A new synthesis of homoallylic cations,,10.1016/s0040-4039(00)90385-x,1964-01-01,0.6568712960338543
Tetrahedron,"A new 3-methylidenepentane-1,5-dianion synthon: synthesis of perhydropyrano[2,3-b]pyrans and 1,7-dioxaspiro[4.5]decanes",,10.1016/j.tetlet.2005.07.077,2005-08-04,0.6568712960338543
Tetrahedron,Synthesis of new analogs of phosphoenol pyruvate,,10.1016/s0040-4039(00)97651-2,1990-01-01,0.6568712960338543
Tetrahedron,A NEW SYNTHESIS OF HYPOGLYCIN A,,10.1016/b978-1-4831-9886-6.50216-3,1963-01-01,0.6568712960338543
Tetrahedron,A new synthesis of δ-lactones from oxetanes,,10.1016/s0040-4039(01)91549-7,1984-01-01,0.6568712960338543
Tetrahedron,A new synthesis of the naphthopyran antibiotics,,10.1016/s0040-4039(00)78878-2,1992-05-01,0.6568712960338543
Tetrahedron,"A new synthesis of (E,E)-tricyclohexaprenol",,10.1016/s0040-4039(00)60879-1,1992-11-01,0.6568712960338543
Tetrahedron,Synthesis of new fluorescently labeled glycosylphosphatidylinositol (GPI) anchors,,10.1016/j.tetlet.2011.06.005,2011-06-25,0.6568712960338543
Synthesis,A New Synthesis of Nitrones,,10.1055/s-1977-24378,1977-01-01,0.6568712960338543
Synthesis,"A New Synthesis of 2-Oxotetrahydro-1,3-thiazoles (2-Thiazolidinones)",,10.1055/s-1977-24380,1977-01-01,0.6568712960338543
Synthesis,"A New Synthesis of ""Nenitzescu's Hydrocarbon""",,10.1055/s-1975-23773,1975-01-01,0.6568712960338543
Tetrahedron,A new synthesis of piperidines and pyridines and pyridines: [3+3] annulation of 2-azaallyl anions,,10.1016/s0040-4039(00)80617-6,1988-01-01,0.6568712960338543
Tetrahedron,A new synthesis of thioflavones,,10.1016/s0040-4039(00)82060-2,1988-01-01,0.6568712960338543
Journal of Organic Chemistry,"A NEW SYNTHESIS OF 3,4-BENZOPHENANTHRENE",,10.1021/jo01373a023,1954-08-01,0.6568712960338543
Tetrahedron,"A new synthesis of γ-alkylidene-Δα,β-butenolides",,10.1016/s0040-4039(01)95206-2,1978-01-01,0.6568712960338543
Synthesis,A New Synthesis of 2-Alkoxy-4-hydroxyquinolines,,10.1055/s-1976-24225,2002-09-12,0.6568712960338543
Tetrahedron,A New Berbine Synthesis,,10.1016/s0040-4039(00)89815-9,1968-01-01,0.6568712960338543
Tetrahedron,A new synthesis of N-arylazetidines,,10.1016/s0040-4039(01)99048-3,1968-01-01,0.6568712960338543
Tetrahedron,"Synthesis of asperenone, a new pigment from and",,10.1016/s0040-4039(01)88611-1,1969-01-01,0.6568712960338543
Tetrahedron,New carbocyclic nucleosides: synthesis of carbocyclic pseudoisocytidine and its analogs,,10.1016/j.tetlet.2014.05.030,2014-05-20,0.6568712960338543
Tetrahedron,A new synthesis of tanikolide,,10.1016/s0040-4039(03)00450-7,2003-03-01,0.6568712960338543
Tetrahedron,"Synthesis of new fluorescent 2-(2′,2″-bithienyl)-1,3-benzothiazoles",,10.1016/j.tetlet.2004.02.048,2004-02-27,0.6568712960338543
Tetrahedron,"A new synthesis of acyclic 1,5-dienes",,10.1016/s0040-4039(01)98609-5,1970-01-01,0.6568712960338543
Tetrahedron,A new convinient synthesis of 3(2H)-furanones,,10.1016/s0040-4039(00)96106-9,1987-01-01,0.6568712960338543
Tetrahedron,A new indolizidine synthesis,,10.1016/s0040-4039(00)95414-5,1987-01-01,0.6568712960338543
Tetrahedron,A new synthesis of flavonols,,10.1016/s0040-4039(01)99420-1,1959-01-01,0.6568712960338543
Tetrahedron,A new synthesis of thiacyclophanes from thiolacetates,,10.1016/0040-4039(94)02491-s,1995-02-01,0.6568712960338543
Tetrahedron,A New Synthesis of Carbapentofuranoses from Carbohydrates,,10.1016/s0040-4039(97)01395-6,1997-09-01,0.6568712960338543
Tetrahedron,A new synthesis of tricyclic sesquiterpene (±)-sterpurene,,10.1016/s0040-4039(01)02224-9,2002-01-01,0.6568712960338543
Tetrahedron,A new synthesis of the cytotoxic alkaloid Luotonine A,,10.1016/s0040-4039(02)00140-5,2002-03-01,0.6568712960338543
Tetrahedron,A new synthesis of 2-nitroindoles,,10.1016/s0040-4039(02)00696-2,2002-05-01,0.6568712960338543
Tetrahedron,Synthesis of new triazepinethiones,,10.1016/s0040-4039(02)01797-5,2002-10-01,0.6568712960338543
Tetrahedron,"New synthesis of 2,2′-heteroarylpyrroles from heteroarylchlorocarbenes",,10.1016/s0040-4039(99)01398-2,1999-10-01,0.6568712960338543
Synthesis,"A New Synthesis of 1,2-Benzocyclohepta-1,3-dien",,10.1055/s-1973-22149,1973-01-01,0.6568712960338543
Tetrahedron,Halogenated ketenes. XIX. 2-alkyltropones: a new synthesis,,10.1016/s0040-4039(01)98431-x,1970-01-01,0.6568712960338543
Synthesis,"A New Synthesis of Pyrido[1,2-<i>a</i>]-1,3,5-triazines",,10.1055/s-1972-21874,1972-01-01,0.6568712960338543
Synthesis,"A New Synthesis of 2-Oxotetrahydro-1,3-thiazine",,10.1055/s-1972-21880,1972-01-01,0.6568712960338543
Tetrahedron,A new synthesis of n-arylsulphonylphyrroles,,10.1016/s0040-4039(01)97967-5,1970-01-01,0.6568712960338543
Tetrahedron,A new entry to the stereocontrolled synthesis of CD rings of Taxol,,10.1016/s0040-4039(97)10347-1,1997-12-01,0.6568712960338543
Tetrahedron,"Synthesis of new 2,3-perfluoroalkyl- and perfluoroaryl-1,4-diazabutadienes (α-diimines)",,10.1016/s0040-4039(99)01692-5,1999-12-01,0.6568712960338543
Tetrahedron,A new synthesis of benzo[f]ninhydrin,,10.1016/s0040-4039(00)96907-7,1987-01-01,0.6568712960338543
Tetrahedron,A new synthesis of phthalides through β-scission of benzocyclobutenol hypoiodites,,10.1016/s0040-4039(00)95515-1,1987-01-01,0.6568712960338543
Synthesis,"A New Synthesis of 5-Arylthieno[2,3-<i>b</i>]pyrroles and 5-Arylthieno [3,2-<i>b</i>]pyrroles",,10.1055/s-1973-22207,1973-01-01,0.6568712960338543
Tetrahedron,A new synthesis of (−)-furodysin,,10.1016/0040-4039(94)02464-m,1995-02-01,0.6568712960338543
Synthesis,A New Synthesis of α-Ketophosphonates,,10.1055/s-2003-37341,2003-01-01,0.6568712960338543
Tetrahedron,A new slippage synthesis,,10.1016/s0040-4039(98)01071-5,1998-07-01,0.6568712960338543
Tetrahedron,A new synthesis of thiazoles from tosylmethylisocyanide and carboxymethyl dithioates,,10.1016/s0040-4039(01)84931-5,1972-01-01,0.6568712960338543
Tetrahedron,A new aporphine synthesis. Photocyclization of a bromophenoxide,,10.1016/s0040-4039(01)97632-4,1971-01-01,0.6568712960338543
Tetrahedron,Dihydrothiopenes. I. A new synthesis,,10.1016/s0040-4039(00)79798-x,1973-01-01,0.6568712960338543
Tetrahedron,A new synthesis of the protoberberine system,,10.1016/s0040-4039(00)81844-4,1983-01-01,0.6568712960338543
Tetrahedron,A new synthesis of beta-carboline,,10.1016/s0040-4039(00)81874-2,1983-01-01,0.6568712960338543
Tetrahedron,A new synthesis of unsymmetrical disulfides,,10.1016/s0040-4039(01)98525-9,1970-01-01,0.6568712960338543
European Journal of Organic Chemistry,Diastereoselective Total Synthesis of (±)‐Toxicodenane A,"The first total synthesis of tricyclic sesquiterpene (±)‐toxicodenane A has been accomplished. This synthetic work was completed in 12 steps from dimedone through diastereoselective reductive desymmetrization of 2,2‐disubstituted 5,5‐dimethylcyclohexane‐1,3‐dione, stereocontrolled allylation, ring‐closing metathesis of a diene compound to yield bicyclic compounds that bear a seven‐membered ring, and construction of the oxygen‐bridged moiety through neighboring group assisted ring‐opening reaction of an epoxide as key steps.",10.1002/ejoc.201701219,2017-10-17,0.6568688943774944
Journal of the American Chemical Society,Scalable Synthesis of Cortistatin A and Related Structures,"Full details are provided for an improved synthesis of cortistatin A and related structures as well as the underlying logic and evolution of strategy. The highly functionalized cortistatin A-ring embedded with a key heteroadamantane was synthesized by a simple and scalable five-step sequence. A chemoselective, tandem geminal dihalogenation of an unactivated methyl group, a reductive fragmentation/trapping/elimination of a bromocyclopropane, and a facile chemoselective etherification reaction afforded the cortistatin A core, dubbed ""cortistatinone"". A selective Δ(16)-alkene reduction with Raney Ni provided cortistatin A. With this scalable and practical route, copious quantities of cortistatinone, Δ(16)-cortistatin A (the equipotent direct precursor to cortistatin A), and its related analogues were prepared for further biological studies.",10.1021/ja202103e,2011-05-03,0.6568635148796312
Tetrahedron,"Synthesis of a 2-benzazepine analog of a potent, nonpeptide GPIIb/IIIa antagonist",,10.1016/0040-4039(94)02273-e,1995-01-01,0.6568466625433234
Organic Letters,"Enantiospecific, Biosynthetically Inspired Formal Total Synthesis of (+)-Liphagal","A biosynthetically inspired synthesis of (+)-liphagal has been achieved from (+)-sclareolide in 13 steps (9% overall yield). The key step is a biomimetic ring expansion of a highly stabilized benzylic carbocation, which generates the seven-membered ring and the benzofuran of the natural product in a single cascade reaction.",10.1021/ol100756z,2010-04-15,0.6568372296315642
Organic Process Research & Development,"Large-Scale Synthesis of Enantio- and Diastereomerically Pure (<i>R</i>,<i>R</i>)-Formoterol","( R, R )-Formoterol ( 1 ) is a long-acting, very potent β 2 -agonist, which is used as a bronchodilator in the therapy of asthma and chronic bronchitis. Highly convergent synthesis of enantio- and diastereomerically pure ( R, R )-formoterol fumarate is achieved by a chromatography-free process with an overall yield of 44%. Asymmetric catalytic reduction of bromoketone 4 using as catalyst oxazaborolidine derived from (1 R, 2 S )-1-amino-2-indanol and resolution of chiral amine 3 are the origins of chirality in this process. Further enrichment of enantio- and diastereomeric purity is accomplished by crystallizations of the isolated intermediates throughout the process to give ( R, R )-formoterol ( 1) as the pure stereoisomer (ee, de >99.5%).",10.1021/op970116o,1998-01-28,0.6568323033562282
Chemical Science,Synthesis of the bis(cyclohexenone) core of (−)-lomaiviticin A,"with respect to the oleandrose residues. While many advances toward the synthesis of lomaiviticin A have been reported, including synthesis of the aglycon, a route to the bis(cyclohexenone) core bearing any of the carbohydrate residues has not been disclosed. Here we describe a short route to a core structure of lomaiviticin A bearing two α-l-oleandrose residues. The synthetic route features a Stille coupling to form the conjoining carbon-carbon bond of the target and a double reductive transposition to establish the correct stereochemistry at this bond. Two synthetic routes were developed to elaborate the reductive transposition product to the bis(cyclohexenone) target. The more efficient pathway features an interrupted Barton vinyl iodide synthesis followed by oxidative elimination of iodide to efficiently establish the enone functionalities in the target. The bis(cyclohexenone) product may find use in a synthesis of lomaiviticin A itself.",10.1039/d0sc02770g,2020-01-01,0.6567723034261648
Synthesis,A Short and Convenient Synthesis of Enantiopure cis- and trans-4-Hydroxypipecolic Acid,"The synthesis of (2S,4R)- and (2R,4R)-4-hydroxypipecolic acid has been realized from commercial ethyl (R)-4-cyano-3-hydroxybutanoate through palladium-catalyzed methoxycarbonylation of a 4-hydroxy-substituted lactam-derived vinyl phosphate followed by the stereocontrolled reduction of the enamine double bond. The stereoselective hydrogenation of the suitably 4-hydroxy-protected enantiomer afforded the cis-(2S,4R)-4-hydroxypipecolic acid product, obtained in 66% overall yield over seven steps. The trans-product (42% overall yield over 8 steps) was instead obtained by hydride conjugate addition to the same alpha,beta-unsaturated ester.",10.1055/s-0029-1216979,2009-08-28,0.6567668960327402
Journal of the American Chemical Society,Enantioselective Total Synthesis of (−)-Chlorothricolide via the Tandem Inter- and Intramolecular Diels−Alder Reaction of a Hexaenoate Intermediate,"An enantioselective total synthesis of (−)-chlorothricolide ( 1 ) has been completed via a route involving the tandem inter- and intramolecular Diels−Alder (IMDA) reaction of hexaenoate 19 and the chiral dienophile ( R )- 12 . This reaction, which establishes seven asymmetric centers in a single operation, is feasible only by virtue of the high diastereofacial and exo selectivity of dienophile 12 . The C(9)-trimethylsilyl steric directing group of 19 also plays a key role by controlling the stereochemical course of the IMDA reaction leading to the bottom half octahydronaphthalene unit. Hexaenoate 19 was prepared in 32% overall yield by a 10-step sequence starting from the known acetylenic ketone 33 . Key steps include the asymmetric reduction of 33 using Alpine Borane (up to 94% ee), the Suzuki cross coupling of α-iodo vinylsilane 20 with vinylboronic acid 21, and the Horner-type olefination of aldehyde 41 with dienylic phosphonate 22 . The key tandem inter-intramolecular Diels−Alder reaction was performed by heating a mixture of 19 and ( R )- 12 (2 equiv) in toluene at 120 °C, which provided the targeted double cycloadduct 44 in 40−45% yield, along with 19% of other cycloadduct isomers and 25−20% of the IMDA adduct 24 with an ( E, E, E )-C(16)−C(21) triene. The latter compound was recycled by treatment with additional ( R )- 12 in trichloroethylene at 125 °C. The yield of 44 from hexaenoate 19 was 55−59% after one recycle of ( E, E, E )- 24 . Elaboration of 44 to (−)-chlorothricolide was accomplished by a 9-step sequence in 26% overall yield, key steps of which included the construction of the spirotetronate subunit of 51 via the Dieckmann cyclization of 50, deprotection of the two allyl units with Pd(0) catalysis, and the BOP-Cl-mediated macrolactonization of seco acid 52 . The vinyl trimethylsilane substituent was removed in the final step of the synthesis by treatment with EtSH and BF 3 ·Et 2 O. Because an authentic sample of chlorothricolide was not available, synthetic (−)-chlorothricolide was treated with CH 2 N 2 to give 24- O -methyl chlorothricolide methyl ester ( 59 ) [[α] 25 D −29.3° ( c = 0.95, CHCl 3 ), mp 228.5−229 °C; lit. 1a [α] D 20 −30° ( c = 1, CHCl 3 ), lit. 1a mp 230 °C)] which proved identical in all respects (except optical rotation and mp) with an authentic sample of racemic 59 provided by Professor Yoshii.",10.1021/ja980611f,1998-07-21,0.6567462351477743
Tetrahedron,Asymmetric pictet-spengler synthesis of tetrahydroisoquinolines. An enantioselective synthesis of (−)-laudanosine.,,10.1016/0040-4039(91)80669-w,1991-06-01,0.6567247244362755
Journal of Organic Chemistry,An Improved Synthesis of (±)-<i>N</i>′-Nitrosonornicotine 5′-Acetate,"A concise and efficient route to (+/-)-N'-nitrosonornicotine 5'-acetate (NNN-5'-OAc), a stable precursor of the active metabolite 5'-hydroxy(+/-)-N'-nitrosonornicotine NNN-5'-OH is reported. The synthesis utilizes sulfinimine chemistry to give (+/-)-NNN-5'-OAc in 26% yield over 4 steps.",10.1021/jo9000417,2009-03-09,0.656716455960997
Tetrahedron,"A new total synthesis of (±)-desacetylcephalothin lactone. A synthesis of novel furo[3,4-c]cephams.",,10.1016/s0040-4039(01)82623-x,1974-01-01,0.6567100093177916
Synthesis,Toward the Total Synthesis ofDisorazole A<sub>1</sub>: Asymmetric Synthesis of the MaskedNorthern Half,The stereoselective synthesis of the masked northern half ofthe antimitotic natural product disorazole A1 is describedinvol­ving as key step a Z-selectiveWittig olefination of a C1-C11 epoxy aldehyde with a C12-C19phosphonium iodide.,10.1055/s-2003-41033,2003-01-01,0.6567041186623667
Tetrahedron,A norbornyl route to azasugars: a new synthesis of deoxynojirimycin analogues,,10.1016/s0040-4039(00)00895-9,2000-07-01,0.6567029572023465
Journal of Organic Chemistry,"Synthesis of (+)-Manoalide via a Copper(I)-Mediated 1,2-Metalate Rearrangement","An enantiospecific synthesis of the phospholipase A(2) inhibitor (+)-(4R)-manoalide is reported in which all 25 carbons of the sesterterpenoid skeleton are constructed from 3-furaldehyde, trimethylalane, oxirane, CO, beta-ionone, and propargyl bromide. The overall yield for the longest linear sequence (12 steps) is 12%. Key steps include (a) a zirconium-catalyzed carboalumination reaction to construct the C10-C11 trisubstituted alkene, (b) a Cu(I)-mediated 1,2-metalate rearrangement to construct the C6-C7 trisubstituted alkene, (c) a Sharpless kinetic resolution to secure the (4R)-stereochemistry, (d) generation of a 5-stannyl-2,3-dihydrofuran by Mo-catalyzed cycloisomerization of a homopropargylic alcohol, and (e) construction of the hydroxyfuranone ring by photooxidation of a silylfuran.",10.1021/jo0268097,2003-04-15,0.6566974960687837
Organic Letters,Enantioselective Synthesis of (+)-Crocacin C. An Example of a Highly Challenging Mismatched Double Asymmetric δ-Stannylcrotylboration Reaction,"A concise, enantioselective synthesis of (+)-crocacin C is described, featuring a highly diastereoselective mismatched double asymmetric δ-stannylcrotylboration of the stereochemically demanding chiral aldehyde 9 with the bifunctional crotylborane reagent (S)-E-10. The total synthesis of (+)-crocacin C was accomplished in seven steps (longest linear sequence) starting from commercially available precursors.",10.1021/ol300476f,2012-03-12,0.6566788701833061
Organic Process Research & Development,Asymmetric Synthesis of the Cyclohexyl Fragment in RORγt Inhibitor (BMS-986251) Enabled by a Dynamic Kinetic Resolution of Hageman’s Ester,"The cyclohexyl fragment 1 in BMS-986251 was synthesized starting from Hagemann’s ester 2 in 7 steps and 5 isolations. The route is highlighted by a dynamic kinetic resolution (DKR), a telescoped enol nonaflation followed by a palladium-catalyzed carbonylation, and a rhodium-catalyzed directed diastereoselective olefin hydrogenation. The optimized process was demonstrated on 1 kg scale, with an overall 51% yield and >99% ee and dr.",10.1021/acs.oprd.1c00339,2021-11-16,0.6566644630742869
Organic Process Research & Development,Kilogram-Lab-Scale Oxindole Synthesis via Palladium-Catalyzed C–H Functionalization,"A scalable method for the preparation of oxindole 8, a key intermediate en route to a serine palmitoyl transferase inhibitor, compound 1, is presented. A three-step, chromatography-free route has been designed that takes advantage of Buchwald’s palladium-catalyzed C–H functionalization to cyclize an α-chloroacetanilide to form the five-membered ring. This process has been successfully carried out in our kilogram laboratory facility on 10-kg scale in 76% yield.",10.1021/op200332p,2011-12-23,0.656660488734011
Organic Letters,"Synthesis of Multisubstituted Furans, Pyrroles, and Thiophenes via Ynolates","An efficient synthetic method for the preparation of multisubstituted furans, thiophenes, and pyrroles using ynolates was developed. This novel formal [4 + 1] annulation by C2-C3 and C3-C4 bond formations includes cycloaddition, cyclization, decarboxylation, and dehydration as key steps.",10.1021/ol0705200,2007-04-17,0.6566378180226233
European Journal of Organic Chemistry,Total Synthesis of Mycophenolic Acid by a Palladium‐Catalyzed Decarboxylative Allylation and Biomimetic Aromatization Sequence,"Abstract This paper describes the total synthesis of the fungal natural product mycophenolic acid through palladium‐catalyzed allylation, biomimetic cyclization, and aromatization. Methyl (4 E )‐6‐hydroxy‐4‐methylhex‐4‐enoate, which was converted in four steps into the key diketo ester dioxinone via two selective C ‐acylation reactions, was transformed into a resorcylate. Subsequent phenol methylation, lactonization, iodo‐ether formation, and halogenation gave a tricyclic intermediate. Palladium‐catalyzed cross‐coupling with DABCO–(AlMe 3 ) 2 and saponification gave mycophenolic acid. An alternative approach with early stage arene methyl incorporation unexpectedly resulted in the formation of a γ‐pyrone.",10.1002/ejoc.201300974,2013-09-24,0.6566242378238608
Journal of Organic Chemistry,The First Total Synthesis of Concanamycin F (Concanolide A),"A highly stereoselective total synthesis of the macrolide antibiotic concanamycin F (1), a specific and potent inhibitor of vacuolar H(+)-ATPase, has been achieved by a convergent route involving the synthesis and coupling of its 18-membered tetraenic lactone and beta-hydroxyl hemiacetal side chain subunits. The C1-C19 18-membered lactone aldehyde 4 was synthesized through the intermolecular Stille coupling of the C5-C13 vinyl iodide 24 and the C14-C19 vinyl stannane 25, followed by construction of the C1-C4 diene and macrolactonization. Synthesis of 4 via a second convergent route including the esterification of the C1-C13 vinyl iodide 45 and the C14-C19 vinyl stannane 47 followed by the intramolecular Stille coupling was also realized. The highly stereoselective aldol coupling of 4 and the C20-C28 ethyl ketone 5 followed by desilylation provided 1 which was identical with natural concanamycin F.",10.1021/jo001377q,2001-02-07,0.6566125479683877
Journal of Organic Chemistry,Toward the Elucidation of the Metabolism of 15-E<sub>2</sub>-Isoprostane: The Total Synthesis of the Methyl Ester of a Potential Central Metabolite,"An 11-step total synthesis of the methyl ester of a potential metabolite of the autoxidatively formed natural product 15-E(2)-IsoP, whose metabolism is not known, is reported. Several vinylogous Mukaiyama aldol additions were tested for the assembly of the acyclic C7-C20 precursor. A new oxidative dianion cyclization served to access the cyclopentane core. The full carbon skeleton was synthesized by an acetylide alkylation. The overall yield of the metabolite amounts to 1.4% for the most efficient route. The results demonstrate convincingly that E(2)-IsoP metabolites are highly epimerization-sensitive and that they may thus also contribute to PGE(2)-action and metabolism.",10.1021/jo1006569,2010-06-09,0.6566066581560129
Journal of Organic Chemistry,The First Total Synthesis of (±)-Huperzine B,"Huperzine B, a new Lycopodium alkaloid, exhibits a memory facilitating effect in mice and may be useful as an acetylcholinesterase inhibitor for the treatment of Alzheimer's disease. An efficient synthetic approach to huperzine B has been established successfully. The tetracyclic intermediate 10 is constructed by means of a tandem Michael addition and intramolecular Mannich cyclization using 8 and 9 as two components. Racemic huperzine B is obtained via a reaction sequence of 12 steps in 6.6% overall yield.",10.1021/jo970248f,1997-08-01,0.6565897832764959
Journal of Organic Chemistry,"Synthesis of Conformationally Constrained Dipeptide Mimetics with Azabicyclo[4,3,0]nonanone and Azabicyclo[5,3,0]decanone Scaffolds","A general and efficient method for the synthesis of azabicyclo[4,3,0]nonanone and azabicyclo[5,3,0]decanone amino acid derivatives was developed with the palladium-catalyzed coupling of intermediates 9 and 10 with BocNH 2 and Boc 2 NH and the following reduction of the C–C double bond by hydrogenation as the key steps. The exploration of the synthesis of C 6 -substituted dipeptide mimetics from 9 and 10 using Suzuki coupling as the key reaction has also been performed.",10.1021/acs.joc.0c00399,2020-07-08,0.6565642099873403
Organic Letters,Five Easy Pieces. The Total Synthesis of Phosphoiodyn A (and Placotylene A),"The convergent total synthesis of the marine natural product phosphoiodyn A, a nanomolar agonist of human peroxisome proliferator-activated receptor delta (hPPARδ), was achieved in five steps total from commercially available and inexpensive starting materials. The synthesis relies on the unprecedented regioselective hydrozirconation of a terminal acetylene in the presence of a conjugated 1,3-diyne and on ammonolysis of a β-chlorophosphonic acid monoester. The scheme also provides the newly isolated placotylene A, an inhibitor of bone marrow-derived macrophage (BMM) differentiation.",10.1021/acs.orglett.5b02642,2015-10-28,0.6565569785111836
Organic Process Research & Development,Asymmetric Fluorination Approach to the Scalable Synthesis of a SYK Inhibitor,"A large-scale process for the synthesis of SYK inhibitor 1 has been developed and used to deliver multi-kilogram yields of this active pharmaceutical ingredient. Integral to the scalable process is a combined chiral auxiliary and chiral catalyst mediated diastereoselective fluorination. Safe processes for BH 3 ·DMS-mediated reduction of ester and amide functions and azide introduction, and a robust Suzuki–Miyaura coupling of a pyrazyl boronate with chloronapthyridine, are described.",10.1021/acs.oprd.5b00131,2015-06-15,0.656544372556383
Organic Letters,Total Synthesis of (−)-Spongidepsin,[structure: see text] A convergent and rapid stereoselective synthesis of (-)-spongidepsin has been achieved from the Roche ester in 14 steps with an overall yield of 13%.,10.1021/ol061029w,2006-07-06,0.6565170346823067
Journal of the American Chemical Society,Total Synthesis of the Duocarmycins,"The total synthesis of (+)-duocarmycin A and SA through a common indoline intermediate is described. The key reactions include selective lithiation of a 2,6-dibromoiodobenzene derivative and diastereoselective addition to a chiral nitroalkene, copper-mediated aryl amination, and addition of aryllithium to azlactones.",10.1021/ja035303i,2003-05-10,0.6564976308451125
Tetrahedron,An efficient asymmetric synthesis of the four stereoisomers of 3-hydroxyleucine,,10.1016/0040-4039(93)88055-n,1993-07-01,0.6564898399138273
Tetrahedron,"An efficient asymmetric synthesis of (2S,3S)- and (2R,3R)-β-hydroxyornithine",,10.1016/s0040-4039(00)01945-6,2001-01-01,0.6564898399138273
Tetrahedron,"An efficient, asymmetric synthesis of (+)-euphococcinine",,10.1016/s0040-4039(00)00665-1,2000-06-01,0.6564898399138273
Tetrahedron,An efficient asymmetric synthesis of grenadamide,,10.1016/j.tetlet.2005.09.087,2005-10-03,0.6564898399138273
Journal of the American Chemical Society,Total Synthesis of (−)-Neocucurbol C Enabled by Pattern Recognition and MHAT Cyclization,"We report an asymmetric total synthesis of (-)-neocucurbol C, a diterpene natural product possessing a unique and complex 6/6/5/5/6 polycyclic skeleton and nine stereocenters. Pattern-recognition analysis led us to the chiral pool molecule (+)-nootkatone as the starting material, already containing the AB ring system and two key stereocenters encoded by the target molecule. The extra isopropenyl group of (+)-nootkatone was removed by Kwon's hydrodealkenylative bond fragmentation. Other key steps include a Suzuki-Miyaura cross coupling to introduce an aromatic ring as the E ring precursor, an oxidative dearomatization cyclization to form the key oxa-bridge, and a metal-catalyzed hydrogen atom transfer (MHAT)-initiated reductive radical cyclization to complete the entire framework for subsequent peripheral decorations, which eventually delivered (-)-neocucurbol C in 24 steps for the first time. In addition, the cytotoxicity evaluation of (-)-neocucurbol C and its synthetic intermediates against multiple cancer cell lines identified new lead compounds with promising anticancer activity for further development.",10.1021/jacs.5c08224,2025-08-04,0.6564725037238642
Tetrahedron,Stereoselective formal synthesis of the potent proteasome inhibitor: salinosporamide A,,10.1016/j.tetlet.2006.11.087,2006-12-05,0.65646509031115
Journal of Organic Chemistry,"Asymmetric Synthesis of <i>trans</i>-2,3-Piperidinedicarboxylic Acid and <i>trans</i>-3,4-Piperidinedicarboxylic Acid Derivatives","Asymmetric syntheses of (2S,3S)-3-(tert-butoxycarbonyl)-2-piperidinecarboxylic acid (1b), (3R,4S)-4-(tert-butoxycarbonyl)-3-piperidinecarboxylic acid (2b), and their corresponding N-Boc and N-Cbz protected analogues 8a,b and 17a,b are described. Enantiomerically pure 1b has been synthesized in five steps starting from L-aspartic acid beta-tert-butyl ester. Tribenzylation of the starting material followed by alkylation with allyl iodide using KHMDS produces the key intermediate 5a in a 6:1 diastereomeric excess. Upon hydroboration, the alcohol 6a is oxidized, and the resulting aldehyde 7 is subjected to a ring closure via reductive amination, providing 1b in an overall yield of 38%. Optically pure 2b has been synthesized beginning with N-Cbz-beta-alanine. The synthesis involves the induction of the first stereogenic center using Evans's chemistry and sequential LDA-promoted alkylations with tert-butyl bromoacetate and allyl iodide. Further elaboration by ozonolysis and reductive amination affords 2b in an overall yield of 28%.",10.1021/jo016086b,2002-01-10,0.6564355372223213
Synlett,A Synthesis of Theopederin D and a Formal Synthesis of Pederin,"All articles of this category Theopederin D, a cytotoxic metabolite from a sponge of the genus Theonella , was synthesised in 14 steps (11.1% overall yield) from two advanced intermediates previously used in a synthesis of mycalamide B. A formal synthesis of pederin from similar intermediates is also reported. antitumour - conjugate addition - asymmetric dihydroxylation - Curtius rearrangement - pederin - theopederin D",10.1055/s-1998-1970,1998-12-01,0.6564219340979758
Synlett,An Efficient Asymmetric Synthesis of Cascarillic Acid,An efficient six-step asymmetric synthesis of the cyclopropane containing natural product cascarillic acid in 41% overall yield is described. The key synthetic steps involve the use of a temporary stereogenic hydroxyl group to control the facial selectivity of a directed cyclopropanation reaction and its subsequent removal via a retro-aldol reaction.,10.1055/s-2006-939690,2006-04-24,0.6564126285437067
European Journal of Organic Chemistry,Synthesis of (+)‐Lentiginosine and Its Pyrrolizidine Analogue Based on Intramolecular Cyclization of α‐Sulfinyl Carbanions,"Abstract A synthesis of (+)‐lentiginosine and its pyrrolizidine analogue was accomplished in six steps, starting from L ‐(+)‐tartaric acid. The key step of these syntheses involves the intramolecular cyclization of α‐sulfinyl carbanions for the construction of the indolizidine or pyrrolizidine ring.",10.1002/ejoc.201301671,2014-01-14,0.6564082197338632
Synthesis,"Synthesis of Daunomycinone<i>via</i>Intramolecular Nucleophilic Addition to 9,10-Anthraquinones","All articles of this category The key intermediate in the synthesis of daunomycinone, compound 6 , is obtained regioselectively in two steps from 1c via alkylation of dimethyl acetonedicarboxylate followed by acidic ester hydrolysis and decarboxylation.",10.1055/s-1986-31831,1986-01-01,0.6563914371630192
Tetrahedron,Highly convergent enantioselective route to trichothecenes,,10.1016/s0040-4039(00)60947-4,1992-10-01,0.6563876343229098
European Journal of Organic Chemistry,"A Diastereoselective Route to <i>trans</i>‐2‐Aryl‐2,3‐dihydrobenzofurans through Sequential Cross‐Metathesis/Isomerization/Allylboration Reactions: Synthesis of Bioactive Neolignans","Abstract A new highly diastereoselective synthetic route to trans ‐2,3‐dihydrobenzofuran systems, in particular those bearing an aryl substituent at the C2 position, is described. The cornerstone of our strategy is the implementation of a cross‐metathesis/isomerization/allylboration sequence starting from 2‐allyl‐substituted phenols and aldehydes. After an intramolecular Mitsunobu cyclization step, the anti ‐homoallylic alcohols allow the synthesis of the desired skeleton in a stereoselective fashion. As an illustration, we used this strategy for the preparation of the dihydrodehydrodiconiferyl alcohol ( 1a ), a natural dihydrobenzofuran neolignan, as well as for a formal synthesis of its O ‐demethylated derivative 1b . An enantioselective version of this approach employing a chiral phosphoric acid in the allylboration step is also studied.",10.1002/ejoc.201500019,2015-02-25,0.6563858803912648
Angewandte Chemie International Edition,Enantioselective Total Synthesis of Hyperforin and Pyrohyperforin,"Abstract Capitalizing on the late‐stage diversification of an essential 1,3‐diene intermediate, we describe herein a 9‐step enantioselective total synthesis of (+)‐hyperforin and (+)‐pyrohyperforin, starting from commercially available allylacetone. Our convergent synthesis features a series of critical reactions: 1) an enantioselective deconjugative α‐alkylation of α,β‐unsaturated acid using chiral lithium amides as noncovalent stereodirecting auxiliaries; 2) a HfCl 4 ‐mediated carbonyl α‐ tert ‐alkylation to forge the intricate bicyclo[3.3.1]nonane framework; 3) an abiotic cascade pyran formation; and 4) a selective 1,4‐semihydrogenation of polyenes. During the course of our synthesis, we also identified a 1,2‐cyclopropanediol overbred intermediate which was responsible for the 1,3‐diene precursor formation through a controlled fragmentation.",10.1002/anie.202116136,2022-02-07,0.6563847998888781
Synlett,Total Synthesis of (-)-Neoechinulin A,A total synthesis of neoechinulin A was accomplished with high enantiomeric excess. Our total synthesis of neoechinulin A established the absolute configuration of natural neoechinulin A. The synthetic route features aldol condensation of a 3-formyl indole derivative and intramolecular cyclization.,10.1055/s-2006-933113,2006-01-01,0.6563781466787952
Synlett,Efficient Total Synthesis of 5-Methoxypsoralen,"A rapid and efficient synthesis of 5-methoxypsoralen, ­furocoumarin commonly used in dermatology for the treatment by PUVA therapy of skin diseases, is described using cheap and easily available starting materials. An alternative method to synthesize 7-(2-oxoethoxy)coumarin, the key step to generate the furan ring, is suggested.",10.1055/s-2006-958420,2006-12-20,0.6563549360357784
Synlett,"Highly Improved Synthesis of (+)-Aureol via (-)-Neoavarone and (-)-Neoavarol, by Employing Salcomine Oxidation and Acid-Induced Rearrangement/Cyclization Strategy","A short and efficient synthesis of (+)-aureol (1), a structurally novel and biologically important marine natural product, was achieved starting with readily available (+)-Wieland-Miescher ketone analogue 7 via (-)-neoavarone (10) and (-)-neoavarol (11). The method features salcomine oxidation of the phenol derivative 9 to deliver 10 and BF3·OEt2-induced rearrangement/cyclization reaction of 11 to produce 1 as the crucial steps. The improved biomimetic synthesis required only 9 steps and proceeds in 31% overall yield.",10.1055/s-2003-37130,2003-01-01,0.6563461860844453
Organic Process Research & Development,Development of a Practical Synthesis of a p38 MAP Kinase Inhibitor,"A practical synthesis of the phthalazine-based p38 MAP kinase inhibitor [( S )- 2 ] was needed for an ongoing program. Vibrational circular dichroism provided the assignment of the absolute stereochemistry of the target compound. The selected synthetic route for ( S )- 2 required identification of efficient reaction conditions for the construction of carbon−oxygen, carbon−carbon, and carbon−nitrogen bonds to connect the key building blocks. An efficient two-step method (chlorodehydroxylation, aromatic nucleophilic substitution) for the synthesis of arylether [( S )- 10 ] was developed. PAT ( in situ Raman spectroscopy) was utilized to monitor and control the formation of a lithium alkoxide in this reaction. The synthesis of ( S )- 2 was completed using high-yielding Suzuki- and amide-coupling reactions. The isolation conditions for these steps were optimized to obtain material of very high purity without the need for any complicated workup procedures.",10.1021/op800250v,2009-01-15,0.6563389161333988
Journal of the American Chemical Society,Enantioselective Total Synthesis of Bistramide A,"The enantioselective synthesis of bistramide A has been achieved with a longest linear sequence of 18 steps. The synthetic strategy involves the use of a distereoselective glycolate alkylation, an aldol addition of a chlorotitanium enolate of N-acylthiazolidinthione, and a Sharpless asymmetric epoxidation to synthesize the three key fragments.",10.1021/ja057686l,2006-03-29,0.6563022576160311
Organic Letters,Total Synthesis of the Proposed Structure of (±)-Nidemone,"Total synthesis of the proposed structure of (±)-nidemone has been accomplished either from 2-hydroxy-6-methoxybenzaldehyde (7) or 2-bromo-6-methoxybenzaldehyde (8) in 10 and 13 synthetic steps, respectively. Sonogashira coupling, regioselective hydrogenation, and an intramolecular Stetter reaction were the key steps in the synthesis.",10.1021/acs.orglett.7b02645,2017-09-29,0.6562810584381805
Synthesis,Convenient Synthesis of Ellagic Acid from Methyl Gallate and SARS-CoV-2 3CLpro Antiviral Activity,"Abstract A practical synthesis of ellagic acid has been achieved from methyl gallate by a proposed synthetic route of five steps, consisting of ketal protection, regioselective bromination, bis-lactonization, C–C bond formation between the aromatic rings of the galloyl groups, and ketal deprotection, in 38% overall yield. Ellagic acid showed a slight inhibitory activity against SARS-CoV-2 3CLpro.",10.1055/a-1941-1437,2022-09-12,0.6562752909796314
Organic Letters,Enantioselective Total Synthesis of (+)-Anthecularin,"An enantioselective total synthesis of (+)-anthecularin, an antiplasmodial and antitrypanosomal sesquiterpene lactone, has been achieved in 3.9% overall yield through 18 steps from a known dibromo alcohol. The key features of the synthesis include an intramolecular Claisen-type cyclization of a formyl-protected hydroxyl lactone to construct a bicyclic intermediate with a quaternary stereogenic center and a stereocontrolled 1,2-addition of vinyllithium to a methoxyethyl-protected spirocyclic hydroxyl enone to install a tetrasubstituted asymmetric center with excellent diastereoselection. This first enantioselective synthesis of anthecularin enabled the determination of its absolute configuration as 2 R, 3 R, 4 S, 8 R.",10.1021/acs.orglett.8b01467,2018-06-04,0.6562615864777562
Tetrahedron,"An efficient synthesis of γ-substituted α,β-unsaturated-δ-lactams. Formal synthesis of (±)-protoemetinol",,10.1016/s0040-4039(02)00401-x,2002-04-01,0.6562279255862736
Journal of Organic Chemistry,Total Synthesis of a Conformationally Constrained Didemnin B Analog,The total synthesis of a didemnin B analogue containing a conformationally constrained replacement for the isostatine moiety is reported. Synthetic highlights include an improved preparation of 2-hydroxy-3-cyclohexenecarboxylic acid and a new strategy for accessing the macrocycle.,10.1021/jo001640n,2001-03-28,0.656222987660691
Journal of the American Chemical Society,Efficient Synthesis of Okadaic Acid. 1. Convergent Assembly of the C15−C38 Domain,"A convergent synthesis of the C15−C38 domain of the marine natural product okadaic acid is reported. This involved the preparation of intermediates representing the C16−C27 and C28−C38 portions of okadaic acid, their direct coupling, and elaboration to the complete C15−C38 intermediate. A C16−C27 intermediate bearing an aldehyde at C27 was constructed in 14-steps from methyl 3- O -benzyl-α- d -altropyranoside. A C28−C38 intermediate with a primary alkyl bromide at C28 was prepared in 10 steps from methyl ( S )-3-hydroxy-2-methylpropionate. These fragments were then joined in ∼55% yield by conversion of the bromide into an alkylcerium reagent then addition to a sensitive β,γ-unsaturated C27 aldehyde to give a mixture of C27 carbinols (27 R:27 S = 2.5:1). The configuration at C27 of the major coupling product was inverted by a simple oxidation−reduction sequence to establish the 27 S -configuration of okadaic acid. Elaboration into a C15 β-keto phosphonate completed the synthesis of the fully functionalized C15−C38 portion of okadaic acid in 19 linear steps and ∼3% overall yield from methyl 3- O -benzyl-α- d -altropyranoside.",10.1021/ja973287h,1998-03-01,0.656212615415063
Journal of Organic Chemistry,Development of a Large Scale Asymmetric Synthesis of the Glucocorticoid Agonist BI 653048 BS H<sub>3</sub>PO<sub>4</sub>,"The development of a large scale synthesis of the glucocorticoid agonist BI 653048 BS H3PO4 (1·H3PO4) is presented. A key trifluoromethyl ketone intermediate 22 containing an N-(4-methoxyphenyl)ethyl amide was prepared by an enolization/bromine-magnesium exchange/electrophile trapping reaction. A nonselective propargylation of trifluoromethyl ketone 22 gave the desired diastereomer in 32% yield and with dr = 98:2 from a 1:1 diastereomeric mixture after crystallization. Subsequently, an asymmetric propargylation was developed which provided the desired diastereomer in 4:1 diastereoselectivity and 75% yield with dr = 99:1 after crystallization. The azaindole moiety was efficiently installed by a one-pot cross coupling/indolization reaction. An efficient deprotection of the 4-methoxyphenethyl group was developed using H3PO4/anisole to produce the anisole solvate of the API in high yield and purity. The final form, a phosphoric acid cocrystal, was produced in high yield and purity and with consistent control of particle size.",10.1021/jo400079z,2013-04-01,0.6562036106389869
Organic Letters,"Enantioselective Total Synthesis of (<i>S</i>)-Bisoranjidiol, an Axially Chiral Bisanthraquinone","The first enantioselective total synthesis of the bisanthraquinone (S)-bisoranjidiol and an unnatural regioisomer has been accomplished. Key features of the synthesis include the asymmetric oxidative biaryl coupling of a hindered 8-substituted 2-naphthol, selective para-quinone formation, and regioselective tandem Diels-Alder/aromatization reactions.",10.1021/ol3001365,2012-02-24,0.6561930736605809
Journal of Organic Chemistry,Formal Synthesis of (±)-Guanacastepene A,"A 17 step synthesis of 55, a late intermediate in Danishefsky's guanacastepene A synthesis, has been completed in 4% overall yield. Key features include the use of vinylmagnesium bromide in the Pd-catalyzed coupling with triflate 13 to give triene 16 without the formation of Heck products, a novel extension of the Stork-Jung vinylsilane Robinson annulation that provides tricyclic 2-hydroxymethylcyclohexenone 42 from 23b in four steps and 51% yield, the ability to obtain almost exclusively alpha'-alkylation of 35ba by the proper choice of protecting groups, and the ability to obtain the desired beta-alcohol selectively by reduction of keto alcohol 42 rather than keto ester 53.",10.1021/jo026702j,2003-01-11,0.656181512996633
Organic Letters,Total Synthesis of Trisaccharide Repeating Unit of <i>Staphylococcus aureus</i> Type 8 (CP8) Capsular Polysaccharide,"Herein, we report a highly efficient total synthesis of Staphylococcus aureus type 8 trisaccharide repeating unit in a lesser number of steps and high stereoselectivity. The complex trisaccharide contains rare amino sugars, viz., d -fucosamine, l -fucosamine, and 2-acetamido d -mannuronic acid. The installation of consecutive sterically hindered 1,2- cis glycosidic linkages, especially β-mannosylation, is the key challenge in this synthesis. The total synthesis of target molecule was completed via a longest linear sequence of 18 steps in 7.1% overall yield.",10.1021/acs.orglett.3c00290,2023-02-28,0.6561674233444622
Organic Process Research & Development,"Development of a Stereoselective Synthesis of (1<i>R</i>,4<i>R</i>)- and (1<i>S</i>,4<i>S</i>)-2-Oxa-5-azabicyclo[2.2.2]octane","Despite the prevalence of morpholine derivatives and bridged heterocycles in medicinally relevant compounds, bridged bicyclic morpholines remain scarce because of the challenges associated with their synthesis. MRK A, an IDH1 mut inhibitor for the treatment of glioma, derives its potency in part from substitution of a zigzag 2,5-bicyclic morpholine, 2-oxa-5-azabicyclo[2.2.2]octane, at C8. While existing entries suffered from low yields and lack of stereochemical control, we developed concise stereospecific routes toward both enantiomers of the zigzag morpholine antipode. The key common intermediate in the two routes was a chiral bicyclic lactone, which was readily synthesized following our previous synthesis of relebactam from optically pure (2 S,5 S )-5-hydroxypiperidine-2-carboxylic acid (HPA). The desired ( R, R ) enantiomer for incorporation into MRK A required inversion of both stereocenters of the bicyclic lactone intermediate, which was accomplished by epimerization via a crystallization-induced diastereomer transformation process followed by a key Ti(O i Pr) 4 -mediated intramolecular S N 2 ring closure. By this method, the ( R, R )-zigzag morpholine was synthesized in six steps from HPA in 25% overall yield.",10.1021/acs.oprd.1c00098,2021-06-07,0.6561471430238419
Tetrahedron,An improved entry to a key intermediate for thienamycin synthesis from methyl ()-3-hydroxybutanoate via direct epimerization at C-3 on 2-azetidinone rings,,10.1016/s0040-4039(00)98775-6,1985-01-01,0.6561290557652305
European Journal of Organic Chemistry,Total Synthesis of the Cyanobacterial Alkaloid Nostodione A,"An efficient total synthesis of the indole alkaloid nostodione A is achieved in seven steps with an overall yield of 38.6%, starting from 1,3‐cyclopentanedione and 1‐iodo‐2‐nitrobenzene. Construction of the novel 3,4‐dihydrocyclopenta[ b ]indole‐1,2‐dione tricyclic intermediate is critical to the proposed synthesis and facilitates rapid access to the natural product. The active methylene group of the tricyclic indole intermediate is harnessed to incorporate the benzylidene moiety through a Knoevenagel condensation. The robustness and scalability of the synthesis enable the preparation of a library of nostodione analogs by merely altering the aldehyde partner. Finally, although nostodione A is classified as an inactive antiproliferative molecule according to the sulforhodamine B assay, unique novel cytotoxic molecules can be easily prepared using the nostodione A framework as an innovative template.",10.1002/ejoc.202500787,2025-12-02,0.6561284738079364
Tetrahedron,Efficient one-step synthesis of 2-hydroxy and 2-aminoglycals from selenoglycosides,,10.1016/s0040-4039(03)01216-4,2003-06-30,0.6561270078883775
Synthesis,"An Efficient One-Step Synthesis of 2-Hydroxy-2,2,6-trimethylcyclohexanone",,10.1055/s-1985-31239,1985-01-01,0.6561270078883775
Organic Process Research & Development,"Practical Synthesis of <i>N</i>-{4-[(2-Methyl-4,5-dihydroimidazo[4,5-<i>d</i>][1]benzazepin- 6(1<i>H</i>)-yl)carbonyl]phenyl}biphenyl-2-carboxamide Monohydrochloride:  an Arginine Vasopressin Antagonist","A novel, reliable, and cost-effective synthetic route to N -{4-[(2-methyl-4,5-dihydroimidazo[4,5- d ][1]benzazepin-6(1 H )-yl)carbonyl]phenyl}biphenyl-2-carboxamide monohydrochloride ( 1, YM087), a potent Arginine vasopressin antagonist, has been developed. Using moisture-controlled potassium carbonate, imidazole formation from α-bromoketone furnished imidazobenzazepine, avoiding potential oxazole-ring formation. Catalytic reduction of nitro imidazobenzazepine afforded the corresponding amine in high yields. Treatment of the imidazole-containing amine directly, with a carbonyl chloride, afforded the target amide circumventing protection of the imidazole.",10.1021/op034079e,2003-11-01,0.6561156363020754
Organic Letters,Total Synthesis of (±)-Cephalosol,"A concise and efficient total synthesis of (±)-cephalosol has been completed (5 steps from known ester 5, 39% overall yield), featuring a Cu(II)-promoted haloisocoumarin formation and sequential Suzuki cross-coupling/intramolecular oxo-Michael addition.",10.1021/ol202923u,2011-11-21,0.6561053152004958
Journal of Organic Chemistry,"A Short, Efficient, and Stereoselective Total Synthesis of a Pyrrolidine Alkaloid:  (−)-Codonopsinine",An efficient total synthesis of antibiotic (-)-codonopsinine 1 with an overall yield of 44% was achieved from d-alanine as a chiral template. The key steps in our strategy are modified Sharpless asymmetric dihydroxylation reaction and the highly stereoselective intramolecular acid-catalyzed amidocyclization.,10.1021/jo061940q,2007-02-23,0.6560968201581603
Journal of Organic Chemistry,Total Synthesis of (−)-Hennoxazole A,"An enantioselective, convergent total synthesis of the antiviral marine natural product (-)-hennoxazole A is completed in 14 steps (longest linear sequence) from commercially available 4-methyloxazole-2-carboxylic acid. Synthesis of the C(1)-C(15) pyran/bisoxazole fragment takes advantage of an aldol-like coupling between a dimethyl acetal and an N-acetylthiazolidinethione for the direct, stereoselective installation of the C(8)-methoxy-bearing stereocenter. A one-pot acetoacetate acylation/decarboxylation/cyclodehydration of another elaborate thiazolidinethione allows for rapid assembly of the pyran-based ring system. Synthesis of the C(15)-C(25) skipped triene side chain fragment makes use of a [2,3]-Wittig-Still rearrangement for efficient installation of the trisubstituted Z-double bond. Key late-stage coupling of the two fragments is effected by deprotonation of the methyl group on the bisoxazole system using lithium diethylamide, followed by alkylation with an allylic bromide side chain segment to form the C(15)-C(16) bond.",10.1021/jo7018015,2007-12-06,0.6560490605496171
Journal of the American Chemical Society,Total Synthesis of Gymnocin-A,"A convergent total synthesis of cytotoxic marine natural polycyclic ether, gymnocin-A (1), is described. The synthesis features three iterations of an oxiranyl anion strategy, involving base-mediated cycloetherification, ring expansion, and reductive etherification, for the construction of the FGH fragment and for its coupling with the ABC and KLMN fragments.",10.1021/jacs.5b10082,2015-11-01,0.6560489746549764
European Journal of Organic Chemistry,A Formal Synthesis of Camptothecin via a Photocatalytic Decarboxylative Radical Addition,"A convergent fragment‐coupling strategy for the synthesis of camptothecin is described. The key step is a photocatalytic decarboxylative radical Michael addition that attaches the ABC rings to the E ring fragment, constructing the main structure of camptothecin in five steps. This work illustrates a new strategy for the synthesis of alkaloids of the camptothecin family.",10.1002/ejoc.201900728,2019-06-30,0.6560478772857373
Organic Letters,Novel Efficient Routes to Indoxyl Glycosides for Monitoring Glycosidase Activities,"A new efficient synthesis for broad access to indoxyl glycosides was developed. Indoxylic acid allyl ester linked to a sugar structure served as the key intermediate in this route. Selective ester cleavage and mild decarboxylation led to the corresponding indoxyl glycosides in good yields. This synthesis was applied for preparation of indoxyl glycosides of fucose, sialic acid, and 6'-sialyl lactose.",10.1021/ol401710a,2013-07-05,0.6560439236285004
European Journal of Organic Chemistry,An Efficient Synthesis of (–)‐Posticlure: The Sex Pheromone of <i>Orgyia postica</i>,"Abstract An efficient multigram synthesis of (–)‐posticlure, the first trans ‐epoxide sex pheromone found in Orgyia postica , from diethyl L ‐tartrate is described. The synthesis was completed in seven steps and 27 % overall yield. The synthetic strategy features double‐Wittig olefination and a stereoselective one‐pot conversion of diol to epoxide as the key steps. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2007)",10.1002/ejoc.200700449,2007-08-07,0.6560371159388976
Synthesis,Efficient and Convenient Syntheses of (<i>R</i>)-(-)-Cryptone and (<i>S</i>)-(-)-4-Isopropenyl-2-cyclohexen-1-one,"All articles of this category Starting with (+)-nopinone (3) ; (R)-(-)-Cryptone (1) and (S)-(-)-4-isopropenyl-2-cyclohexen-1-one (2) were synthesized in five steps and 42% overall yield, and four steps and 49% overall yield, respectively.",10.1055/s-1992-26297,1992-01-01,0.6560335987198548
Organic Letters,A Convergent Route to the CDEF-Tetracycle of Pectenotoxin-2,"A convergent synthesis of the CDEF-tetracyclic region of pectenotoxin-2 (PTX-2) is described. The synthetic pathway derives from a head-to-tail union of 2 equiv of linalool to establish a stereodefined DEF-tricyclic aldehyde. Subsequent coupling with a ""northern"" fragment enolate, followed by a tandem Sharpless epoxidation/cyclization, delivers the C10-C26 polycyclic region of the natural product.",10.1021/ol200627d,2011-04-08,0.6560279468459738
Journal of the American Chemical Society,Enantioselective Total Synthesis of (+)-Corymine and (−)-Deformylcorymine,"We report herein the first enantioselective total synthesis of akuammiline alkaloids (+)-corymine and (−)-deformylcorymine. Starting from commercially available N -nosyltryptamine, the target molecules are both achieved in 11 steps. Key elements of the design include (a) a copper-catalyzed enantioselective addition of dimethyl malonate to a 3-bromooxindole to secure the C7 all-carbon quaternary stereocenter, (b) a one-step construction of cyclohexyl and pyrrolidinyl rings via intramolecular nucleophilic C- and N-addition, and (c) a nickel-promoted 7- endo cyclization of alkenyl bromide to furnish the azepanyl ring. The strategy is further extended to the synthesis of another three members of the akuammiline family, namely, (−)-10-demethoxyvincorine, (−)-2( S )-cathafoline, and (−)-3- epi -dihydrocorymine 17-acetate.",10.1021/jacs.0c00302,2020-01-28,0.6560123300468638
Journal of the American Chemical Society,Enantioselective Synthesis of (+)-Peganumine A,"A gram-scale enantioselective total synthesis of (+)-peganumine A was accomplished in 7 steps from commercially available 6-methoxytryptamine. Key steps included (a) a Liebeskind-Srogl cross-coupling; (b) a one-pot construction of the tetracyclic skeleton from an ω-isocyano-γ-oxo-aldehyde via a sequence of an unprecedented C-C bond forming lactamization and a transannular condensation; (c) a one-pot organocatalytic process merging two achiral building blocks into an octacyclic structure via a sequence of enantioselective Pictet-Spengler reaction followed by a transannular cyclization. This last reaction created two spirocycles and a 2,7-diazabicyclo[2.2.1]heptan-3-one unit with excellent control of both the absolute and relative stereochemistry of the two newly created quaternary stereocenters.",10.1021/jacs.6b07846,2016-08-25,0.6560093559537837
Organic Letters,<i>De Novo</i> Asymmetric Synthesis of Fridamycin E,"A de novo asymmetric synthesis of (R)- and (S)-fridamycin E has been achieved. The entirely linear route required only nine steps from commercially available starting materials (16% overall yield). Key transformations included a Claisen rearrangement, a Sharpless dihydroxylation and a cobalt-catalyzed epoxide carbonylation to give a β-lactone intermediate. Antibacterial activities were determined for both enantiomers using two strains of E. coli, with the natural (R)-enantiomer showing significant inhibition against a Gram-(+)-like imp strain (MIC = 8 μM).",10.1021/ol203041b,2011-11-22,0.6560055834607561
Journal of the American Chemical Society,Total Synthesis of Caesalpinnone A and Caesalpinflavan B: Evolution of a Concise Strategy,"The total syntheses of caesalpinnone A (1) and its putative biosynthetic precursor caesalpinflavan B (3) are described. Herein, we describe the evolution of a synthetic strategy toward 1 and 3, which entails a convergent Barluenga coupling that quickly delivers a heavily functionalized benzopyran containing the core carbon framework and exploration of two distinct synthetic routes for forging the flavanoid C-ring by reducing a sterically encumbered embedded alkene: one via a stepwise approach and a second, more direct and atom-economical, enabled by a Shenvi-HAT hydrogenation. The latter strategy allowed access to caesalpinflavan B in 6 steps after Pd-mediated deallylation. A late-stage dearomative phenolic oxidation and deallylation/oxa-Michael cascade was implemented to access caesalpinnone A (1) in 7 steps. We also describe an enantioselective total synthesis and stereochemical revision of (-)-caesalpinflavan B, as well as a formal enantioselective synthesis of (-)-caesalpinnone A, by implementing an enantioselective Pd-catalyzed conjugate addition developed by Stoltz.",10.1021/jacs.9b04472,2019-05-30,0.6560033786804437
Tetrahedron,A novel stereoselective synthesis of a chiral key intermediate for the preparation of vitamin D3,,10.1016/s0040-4039(01)91090-1,1984-01-01,0.6559956595104086
Synthesis,"A Novel Route to 4<i>H</i>-1,4-Benzothiazines by Ring-Expansion of 2,3-Dihydro-1, 3-benzothiazoles",,10.1055/s-1977-24616,1977-01-01,0.6559665992493019
Organic Letters,"Total Syntheses of Naucleamides A–C and E, Geissoschizine, Geissoschizol, (<i>E</i>)-Isositsirikine, and 16-<i>epi</i>-(<i>E</i>)-Isositsirikine","A divergent approach for the enantioselective total synthesis of eight monoterpenoid indole alkaloids was developed. The approach allows the first total syntheses of naucleamides A-C and E in only 6-8 steps and also enables the efficient synthesis of geissoschizine, geissoschizol, (E)-isositsirikine, and 16-epi-(E)-isositsirikine in 10-11 steps from commercially available crotonic aldehyde. The synthesis features a one-pot organocatalyzed asymmetric Michael addition/Pictet-Spengler reaction. Notably, biomimetic synthesis of naucleamide E was achieved by oxidative cyclization of naucleamide A.",10.1021/acs.orglett.7b00983,2017-05-03,0.6559664073473674
Synlett,Enantioselective Stereodivergent Synthesis of Jaspine B and 4-epi-Jaspine B from Axially Chiral Allenols,"A short enantioselective synthetic route to the cytotoxic marine natural product jaspine B has been developed. A chiral non-racemic primary α-allenol, obtained from pentadecanal, gave access to an enantioenriched 2-tetradecyl-2,5-dihydrofuran as key intermediate. A stereodivergent functionalization of this dihydrofuran allowed access in a few steps to jaspine B and its 4-epimer.",10.1055/s-0037-1610344,2018-12-06,0.6559489660071295
Organic Letters,Total Synthesis of Conulothiazole A,An efficient total synthesis of the chlorinated thiazole-containing natural product conulothiazole A is reported. Key features of this synthesis include a novel rhodium-catalyzed enantioselective hydrogenation of a 2-enamido-thiazole and a vinylic Finkelstein reaction that could be implemented at all stages of the synthesis to install the chlorinated alkene.,10.1021/acs.orglett.9b01490,2019-05-23,0.6558857181244077
Organic Process Research & Development,Exploratory Process Development and Kilogram-Scale Synthesis of a Novel Oxazolidinone Antibacterial Candidate,"A concise, environmentally benign, and cost-effective route was developed for the large-scale preparation of 1, a novel oxazolidinone antibacterial candidate. The key intermediate 2-(1-(2-fluoro-4-nitrophenyl)-1 H -pyrazol-4-yl)pyridine 7 was prepared with high purity by mild deamination of the regioisomeric mixture 21 . The mixture was prepared from a nucleophilic SNAr reaction by selective C–N coupling of the secondary amine functionality of 4-(pyridin-2-yl)-1 H -pyrazol-3-amine 14 with 1,2-difluoro-4-nitrobenzene 10 in optimized conditions with the primary amine group remaining intact. The gaseous nitrogen release rate and reaction mixture temperature of the deamination step can be well controlled by altering the feeding manner, thereby providing safety guarantees. The optimized synthetic strategy of 1 with an overall yield of 27.6%, including seven sequential transformations by only five solid–liquid isolations, significantly improved the product separation workup. The strategy bypassed time-consuming and laborious procedures for any intermediate involved as well as for the final API. This study presents a process enabling the rapid delivery of a multikilogram quantity of API with high purity.",10.1021/op500030v,2014-03-03,0.655883737712068
Tetrahedron,Diastereoselective synthesis of the key lactone intermediate for the preparation of hydroxyethylene dipeptide isosteres,,10.1016/s0040-4039(00)75834-5,1994-01-01,0.6558591988700737
Tetrahedron,"A novel and efficient synthesis of cyclic and acyclic 1,5-alkadiynes by selective coupling of Co2(CO)6-complexed propargyl radicals",,10.1016/0040-4039(94)85054-2,1994-01-01,0.6558583710161148
Synlett,Formal Synthesis of Pseudolaric Acid B,"A formal synthesis of pseudolaric acid B, a diterpene isolated from the root bark of Pseudolarix kaempferi Gordon (Pinaceae), to Trost’s synthetic intermediate was achieved in 17 steps from a known ketone. Key features of this synthesis include a Claisen rearrangement and iodoetherification to construct quaternary stereocenters and ring-closing metathesis to form the seven-membered ring.",10.1055/s-0039-1690829,2020-02-18,0.6558436816868601
Organic Letters,Total Synthesis of (+)-Nivetetracyclate A,"A stereoselective synthetic approach to the natural product (+)-nivetetracyclate A is reported. The tetracyclic skeleton was assembled in a convergent manner by an alkylation to a diarylmethane and subsequent Friedel-Crafts acylation. Further key steps are an asymmetric Sharpless epoxidation and the boron trifluoride-mediated diastereoselective rearrangement of an epoxy alcohol to a β-hydroxy aldehyde. Optimized timing for the deprotection step and the chemo- and stereoselective Noyori -transfer hydrogenation of a 1,4-diketone allowed the late stage introduction of the C4 stereocenter.",10.1021/acs.orglett.8b04044,2019-01-16,0.6558157503745508
Synlett,Concise Total Synthesis of Curvulone B,"Abstract A concise and convergent stereoselective synthesis of curvulone B is described. The synthesis utilized a tandem isomerization followed by C–O and C–C bond-forming reactions following Mukaiyama-type aldol conditions for the construction of the trans-2,6-disubstituted dihydropyran ring system as the key steps. Other important features of this synthesis are a cross-metathesis, epimerization, and Friedel–Crafts acylation.",10.1055/a-1297-6838,2020-10-26,0.6558084006301944
Journal of Organic Chemistry,Concise Total Synthesis of (+)-Aspergillide B,"An efficient total synthesis of (+)-aspergillide B has been achieved, which features the C-glycosylation reaction for constructing the 2,6-trans-substituted pyran core, a highly effective four-step sequence without purification to produce the key intermediate 13 and an advantegous E-selective Julia-Kocienski olefination on a highly elaborate substrate. The synthesis confirmed the revised structure of aspergillide B by Uenishi.",10.1021/jo900820f,2009-06-01,0.6557867549553369
Tetrahedron,"Titanium-mediated reductive cross-coupling reactions of imines with nitriles: an efficient route for the synthesis of α-aminoketones or 1,2-diketones",,10.1016/j.tetlet.2014.01.070,2014-01-25,0.655774437407148
Journal of the American Chemical Society,"Synthetic Studies of the Tunicamycin Antibiotics. Preparation of (+)-Tunicaminyluracil, (+)-Tunicamycin-V, and 5'-epi-Tunicamycin-V","A concise synthetic route to the tunicamycin antibiotics is described, illustrated by the preparation of (+)-tunicamycin-V (1-V), Key features of the synthesis include (1) the development and application of a silicon-mediated reductive coupling of aldehydes and allylic alcohols to construct the undecose core of the natural product and (2) the development of an efficient procedure for the synthesis of the trehalose glycosidic bond within the antibiotic. These innovations allow for the coupling of a uridine-derived aldehyde fragment with a performed trehalose-linked disaccharide allylic alcohol to form the carbohydrate core (1) of the natural product in a highly covergent manner. The resultant amino polyol is a versatile intermediate for the synthesis of any of the homologous tunicamycin antibiotics.",10.1021/ja00090a018,1994-06-01,0.6557499076471022
Organic Process Research & Development,A Facile Route of Synthesis for Making Flibanserin,A novel and efficient route of synthesis for making flibanserin via 2-ethoxy-1 H -benzo[ d ]imidazole ( 12 ) was described with excellent yield. This protocol provided a more facile approach to flibanserin.,10.1021/acs.oprd.6b00108,2016-07-26,0.6557127793717845
Journal of the American Chemical Society,Enantioselective Total Synthesis of (+)-Arboridinine,"The enantioselective total synthesis of cage-shaped alkaloid (+)-arboridinine is reported. The synthesis takes advantage of the stereoselective double-Mannich reaction to rapidly construct the aza[3.3.1]bicyclic core along with two quaternary stereocenters of the alkaloid. Key steps for the present synthesis include an enantioselective Michael addition establishing the original chiral center at C10 and intramolecular dearomative alkylation forging the cage-shaped ring system found in arboridinine, as well as creating the requisite quaternary carbon center at C3. The bridgehead hydroxyl moiety at C11 was installed through a late-stage cobalt-catalyzed decarboxylative acetoxylation reaction. This strategy enables a 14-step asymmetric total synthesis of (+)-arboridinine from the readily available starting materials with most of the transformations performed on the decagram scale.",10.1021/jacs.9b02362,2019-04-08,0.6557043201805004
Organic Letters,Total Synthesis of Thromboxane B<sub>2</sub> via a Key Bicyclic Enal Intermediate,"A 12-step asymmetric synthesis of thromboxane B 2 (TxB 2 ) from 2,5-dimethoxytetrahydrofuran is described. The synthesis employs our organocatalytic aldol reaction of succinaldehyde to give a key bicyclic enal intermediate. From here, the synthetic strategy involves a conjugate addition of an alkenyl side chain to the bicyclic enal, Baeyer–Villiger oxidation, and a highly Z -selective Wittig olefination of a hemiacetal. Key to success was minimizing redox operations and the manipulation of functional groups in the correct order.",10.1021/acs.orglett.0c02299,2020-08-07,0.6556995094398258
Organic Letters,Enantioselective Synthesis of (−)-LL-C10037α from Benzoquinone,The enantioselective total synthesis of the Streptomyces metabolite (−)-LL-C10037α has been accomplished in 10 steps and 20% overall yield. An early chiral intermediate was resolved with Candida rugosa lipase to provide (+)- 5 with an enantiomeric excess ≥98%. The synthesis is notable in that no protecting groups are required and that all carbons in the core structure of LL-C10037α are derived from the readily available p -benzoquinone.,10.1021/ol991038n,1999-10-02,0.6556677897391233
Organic Process Research & Development,"Process Chemistry Related to the Experimental Rice Herbicide 2,2-Dimethyl-1-(4-methylthio-5-pyrimidinyl)indane","Two concise syntheses of the experimental rice herbicide 2,2-dimethyl-1-(4-methylthio-5-pyrimidinyl)indane are reported. The initial synthesis relies on a low-temperature addition of 5-lithio-4-methylthiopyrimidine to 2,2-dimethyl-1-indanone to construct the pyrimidinylindane system. Process improvements to this route are described and resulted in the preparation of 90 kg of the title compound on pilot plant scale. Economics dictated the need to identify a new synthetic route which utilized inexpensive raw materials. Detailed herein is the initial discovery of a new route which features a novel combination of dissolving metal reduction/formylation/cyclization to construct the requisite pyrimidine ring. Process improvements to this chemistry have allowed us to deliver an appropriately substituted pyrimidinylindane in a minimal number of synthetic operations.",10.1021/op000033z,2000-06-20,0.6556628160465118
Journal of Organic Chemistry,"Short Synthesis of the Seed Germination Inhibitor 3,4,5-Trimethyl-2(5<i>H</i>)-furanone","3,4,5-Trimethyl-2(5H)-furanone, a new seed germination inhibitor with very promising agrochemical applications, was efficiently synthesized from 2,3-dimethylmaleic anhydride via nucleophilic addition of methyllithium followed by reduction using sodium borohydride. This two-step synthesis is straightforward and high-yielding and permits the large-scale preparation of the seed germination inhibitor.",10.1021/jo1010476,2010-07-20,0.6556480609394395
Organic Letters,"Enantioselective Synthesis of a Highly Potent Selective Serotonin Reuptake Inhibitor. An Application of Imidazolidinone Catalysis to the Alkylation of Indoles with an α,β-Disubstituted α,β-Unsaturated Aldehyde","The synthesis of the highly potent and selective serotonin reuptake inhibitor 1 (BMS-594726) is described. In the key construction step, an enantioselective alkylation of the indole nucleus with an alpha-branched alpha,beta-unsaturated aldehyde 7 was accomplished utilizing MacMillan's imidazolidinone catalyst 3b. A rationale is presented for the unexpected stereochemical result, as well as the novel reactivity of the alpha-branched substrate. [reaction: see text]",10.1021/ol051000c,2005-07-08,0.6556324716193843
Journal of the American Chemical Society,4-Aryloxybutenolides As “Chiral Aldehyde” Equivalents:  An Efficient Enantioselective Synthesis of (+)-Brefeldin A,"4-(2'-Naphthoxy)-2-butenolide, readily available with high enantiopurity by a dynamic kinetic asymmetric transformation (DYKAT) of racemic 4-acyloxybutenolides (available in two steps from furfural), serves as an excellent chiral building block where the naphthoxy group strongly directs the stereochemistry of cycloadditions to the double bond. Notably, the cycloadditions of trimethylenemethanepalladium intermediates which do not exhibit good diastereoselectivity in additions to acceptors that possess many common and important chiral auxiliaries undergo cycloadditions with excellent regio- and stereocontrol. The utility of this process set the stage for an efficient new synthesis of (+)-brefeldin A, a compound of growing pharmacological significance. This synthesis also highlights the Pd-catalyzed DYKAT of crotyl carbonate to create the remote stereocenter. A new two-step method to convert aldehydes to delta-hydroxy-E-alpha,beta-enoates is also outlined.",10.1021/ja026438b,2002-07-18,0.6556113452381753
Organic Letters,A Concise Route to the Azaspirodecane Moiety of Halichlorine and Structurally Related Alkaloids,"[reaction: see text] A tandem Michael addition-enolate alkylation followed by Dieckmann cyclization and Beckmann rearrangement provided the corresponding [5.4.0] azaspirobicyclodecane, a key intermediate in our synthetic route to the marine alkaloid halichlorine (1).",10.1021/ol050306g,2005-03-19,0.655610864801322
Tetrahedron,"Synthesis and structure revision of the myo-inositol monophosphatase inhibitor L-671,776",,10.1016/s0040-4039(97)01146-5,1997-07-01,0.6556005546392246
Synlett,Asymmetric Synthesis of C<sub>2</sub>-Symmetric Annulated Bicyclooctylcyclopentadienes,"All articles of this category The efficient asymmetric preparation of the C 2 -symmetric annulated cyclopentadienes, (+)-(1 R ,7 R ,8 R ,10 R )-8, 10-diisopropyltricyclo[5.2.2.0 2,6 ]undeca-2,5-diene ( 1 ) and (-)-(1 S ,7 S ,8 R ,10 R )-8,10-dimethyltricyclo [5.2.2.0 2,6 ]undeca-2,5-diene( 2 ) is described. The key step in these syntheses is an asymmetric dihydroboration of 1,4-dialkyl-1,4-cyclohexadienes using enantiomerically pure isopinocamphenylborane. The overall yield of enantiomerically enriched 1 or 2 is 27% and 20%, respectively, for the five-step synthesis (Birch reduction of 1,4-dialkylbenzene, asymmetric dihydroboration-oxidation, bis(methanesulfonate) formation, bisalkylation of cyclopentadiene, and [1,5]-sigmatropic rearrangement). The formation of chiral titanocene dichlorides is described.",10.1055/s-1990-21001,1990-01-01,0.6555438373424355
Synthesis,Total Synthesis of 4-Ketoclonostachydiol,"A facile total synthesis of nonsymmetrical 14-membered macrocyclic bis-lactone, 4-ketoclonostachydiol has been demonstrated in a convergent approach. The synthetic strategy has been unambiguously successful towards incorporating all the three stereogenic centers present in the molecule with an overall yield of 0.9%. The key synthetic step includes MacMillan hydroxylation and Grubbs ring-closing metathesis reactions to furnish the core skeleton.",10.1055/s-0033-1339121,2014-06-12,0.6555076152696371
Synthesis,"Solvent-Free Synthesis of Bis(2,2′:6′,2′′-terpyridin-4′-yl)amine and Its Metal Complexes","The key compound bis(2,2′:6′,2′′-terpyridin-4′-yl)amine was prepared in one step starting from 4′-amino-2,2′:6′,2′′-terpyridine and 4′-bromo-2,2′:6′,2′′-terpyridine in quantitative yield. In addition, we have established an easy and efficient route for the synthesis of the bromoterpyridine compound. Using the novel ligand, two ruthenium complexes were also prepared.",10.1055/s-2008-1072574,2008-05-01,0.6555000623662732
Journal of Organic Chemistry,Total Synthesis of (−)-Martinellic Acid via Radical Addition−Cyclization−Elimination Reaction,"The asymmetric total synthesis of martinellic acid, the first pyrrolo[3,2-c]quinoline alkaloid found in nature, is described. Three key steps in our synthesis of (-)-martinellic acid are the Bu(3)SnH-promoted radical addition-cyclization-elimination (RACE) reaction of an oxime ether with an alpha,beta-unsaturated ester to generate the pyrrolo[3,2-c]quinoline core, a chemoselective lactam carbonyl reduction, and guanidinylation under Mitsunobu reaction conditions. The key radical cyclization has also been investigated by using SmI(2). (-)-Martinellic acid was synthesized from commercially available methyl 4-bromo-3-methylbenzoate in fewer steps than previous syntheses and in an improved overall yield.",10.1021/jo800560p,2008-05-13,0.655495659769176
Synthesis,A Short and Scalable Synthesis of Orthogonally Protected Bis(aminomethyl)malonic Acid: Access to Bioactive Macrocyclic Peptides,"A short and scalable process for the preparation of multi-gram quantities of orthogonally protected bis(aminomethyl)malonic acid in good yield from readily available starting material is described. These orthogonally protected amino acids are important building blocks to make peptides based drugs, glycoconjugates, and in the total synthesis of peptide natural products. The newly developed route has only six steps with an overall yield of 27%, which involves nucleophilic attack of a malonate on an imide as one of the key steps.",10.1055/s-0036-1588505,2017-08-01,0.6554930136273962
Tetrahedron,An efficient strategy for the synthesis of 5-hydroxyalkylbutan-4-olides from d-mannitol: total synthesis of (−)-muricatacin,,10.1016/s0040-4039(02)00375-1,2002-04-01,0.6554837966687754
Synthesis,Asymmetric Synthesis of Netarsudil: A New Therapeutic for Open-Angle Glaucoma,"The asymmetric synthesis of a Rho kinase/norepinephrine transport inhibitor, netarsudil, the active component in the recently FDA-approved product Rhopressa™, is described herein. This concise six-step synthetic route utilizes the 2,4-dimethylbenzoate ester of a phenylacetic acid as the backbone of the β-amino acid’s framework. A chiral enolate of the Evans auxiliary, (R)-4-benzyloxazolidin-2-one, is used to direct the formation of the (S)-stereocenter by incorporating the N-Boc-protected β-amino methyl arm with high diastereoselectivity (96:4 dr) using N-Boc-1-aminomethylbenzotriazole as the electrophile. Uniquely, 2,2,2-trichloro-1,1-dimethylethyl chloroformate is used as a non-racemizing activating agent for the coupling reaction between the chiral (S)-N-Boc-protected 2,4-dimethylbenzoyloxymethyl phenyl propanoic acid and 6-aminoisoquinoline to provide N-Boc-protected netarsudil in good yield and excellent enantiomeric purity (63%, 98% ee). Final acidic deprotection and recrystallization provides netarsudil (&gt;99% ee), an ophthalmic agent used for the treatment of patients with open-angle glaucoma.",10.1055/s-0037-1610310,2018-10-29,0.6554586763951945
Journal of Organic Chemistry,Biomimetic Total Synthesis of (+)-Chabranol,"A concise, biomimetic total synthesis of the unprecedented terpenoid skeleton (+)-chabraol has been accomplished via 6 steps from the chiral epoxide 7, involving an intramolecular Prins double cyclization to yield the bicyclo[2.2.1] core of the natural product as the key step. The absolute configuration of natural chabranol was also designated through the first asymmetric total synthesis.",10.1021/jo101016g,2010-07-13,0.6554573061988164
Organic Process Research & Development,"Process Development of CP-481715, a Novel CCR1 Antagonist","Process development for the synthesis of 2-quinoxalinecarboxamide, N -[(1 S,2 S,4 R )-4-(aminocarbonyl)-1-[(3-fluorophenyl)methyl]-2,7-dihydroxy-7-methyloctyl] is described. An optimized and streamlined process starting from lactone 2 was developed: Lactone 2 was alkylated diastereoselectively with prenyl bromide, followed by deprotection of the N -Boc group and concomitant hydration of the olefin. Aminolysis of the lactone in methanolic ammonia afforded the titled compound.",10.1021/op050059w,2005-06-04,0.6554288388441452
Tetrahedron,Synthetic studies on cervinomycin: An efficient synthesis of ring ABCD of cervinomycin.,,10.1016/s0040-4039(00)80401-3,1988-01-01,0.6554268678329082
Journal of Organic Chemistry,Diastereoselective Allylation in the Divergent Total Syntheses of Guaianolides (+)-Ligustrin and (+)-Grosheimin and the Formal Synthesis of (−)-Eupalinilide E,"An efficient diastereoselective allylation of aldehydes with functionalized allyl bromolactone paved an excellent path toward the protecting-group-free divergent total synthesis of various guaianolides (+)-ligustrin, (+)-8- epi -ligustrin, and (+)-grosheimin and the formal synthesis of (−)-eupalinilide E. The key steps include diastereoselective allylation, efficient translactonization, and aldehyde–ene reaction. From the common intermediate molecule (+)-ligustrin, the first asymmetric total synthesis of (+)-grosheimin has been achieved.",10.1021/acs.joc.2c02094,2022-10-24,0.6554052200710284
European Journal of Organic Chemistry,Stereoselective and Regioselective Preparation of <i>C</i>‐Pentopyranosides and Formal Synthesis of Omarigliptin,"A readily available intermediate obtained from d ‐arabinose was identified as a versatile starting material for the stereoselective synthesis of C ‐pentopyranosides in one pot. For two of the C ‐pentopyranosides, subsequent epoxide ring formation and a regioselective opening process was proven to be a robust approach to 3‐deoxy C ‐pentopyranosides in two to four steps. A key intermediate used in the preparation of omarigliptin was obtained in four steps. Most of the conversions were high‐yielding and proceeded with high selectivities on a multigram scale.",10.1002/ejoc.201601074,2016-10-17,0.6553976357608402
Organic Letters,Efficient and Scalable Synthesis of Bardoxolone Methyl (CDDO-methyl Ester),"Bardoxolone methyl (2-cyano-3,12-dioxooleane-1,9(11)-dien-28-oic acid methyl ester; CDDO-Me) (1), a synthetic oleanane triterpenoid with highly potent anti-inflammatory activity (levels below 1 nM), has completed a successful phase I clinical trial for the treatment of cancer and a successful phase II trial for the treatment of chronic kidney disease in type 2 diabetes patients. Our synthesis of bardoxolone methyl (1) proceeds in ∼50% overall yield in five steps from oleanolic acid (2), requires only one to two chromatographic purifications, and can provide gram quantities of 1.",10.1021/ol400399x,2013-03-26,0.6553925738365202
Synlett,Total Synthesis of Avermectin B1a: Synthesis of the Carbohydrate<i>Bis</i>-Oleandrose Fragment and Coupling to the Avermectin B1a Aglycone,"All articles of this category A synthesis of the bis -oleandrose fragment of avermectin B1a ( 1 ) is described, involving π-allyl tricarbonyliron lactone complexes as key synthetic intermediates. Final glycosidation to the aglycone employed the use of an imidazolylthiocarbonyl glycoside, to conclude the total synthesis of avermectin B1a.",10.1055/s-1990-21081,1990-01-01,0.6553854001596459
Journal of the American Chemical Society,An Asymmetric Route to the Conanine BCDE Ring System. A Formal Total Synthesis of (+)-Conessine,"The first enantioselective synthesis of the known (+)-conessine precursor (+)-benzohydrindan 23 from the chiral nonracemic bicyclic lactam 1 is described. The key transformation was the highly diastereoselective (3 + 2) cycloaddition of azomethine ylide 11a to lactam 7 in order to construct the pyrrolidine E ring system at any early stage in the synthesis. The requisite pyrrolidine methyl group at C-21 was stereoselectively installed late in the synthesis by lithiation of N -Boc-pyrrolidine intermediate 20 with sec -BuLi/TMEDA followed by quenching at −90 °C with iodomethane, furnishing the tetracyclic pyrrolidine 21 . Reduction of t -Boc 21 with lithium aluminum hydride affords (+)- N -methyl tetracycle 23 in a concise 13-step synthesis from 1 .",10.1021/ja961903o,1996-01-01,0.6553826158569985
Tetrahedron,A new route to 3-hydroxyphthalides : Application to the synthesis of racemic [5-13C] daunomycinone.,,10.1016/s0040-4039(00)84815-7,1986-01-01,0.6553794586680636
Organic Process Research & Development,"An Efficient Synthesis of 2-Hydroxyethyl <i>N,N,N</i><i>‘</i><i>,N</i><i>‘</i>-Tetrakis(2-chloroethyl)phosphorodiamidate","A process for the multikilogram preparation of 2-hydroxyethyl N, N, N ‘, N ‘ -tetrakis(2-chloroethyl)phosphorodiamidate has been achieved in substantially pure form by a short synthetic sequence starting from phosphorus oxychloride and 2 equiv of bis(2-chloroethyl)amine. This process involves a two-step preparation of the intermediate mustard chloride in one pot, followed by the base-catalyzed reaction with excess ethylene glycol. This method has been carried out to provide 2.9 kg of this key drug substance intermediate in 52% overall yield.",10.1021/op010208k,2001-05-17,0.6553751104397488
Synthesis,"A Novel Asymmetric Synthesis of the Core Octadienoic Acid Unit of Cryptophycins from (R)-2,3-O-Cyclohexylideneglyceraldehyde","A facile asymmetric synthesis of the octadienoic acid unit of cryptophycins was developed starting from (R)-2,3-O-cyclohexylideneglyceraldehyde. The key steps of the synthesis are the stereocontrolled generation of the required asymmetric centers through (i) a gallium-mediated highly diastereoselective crotylation of the glyceraldehyde in [bmim][Br], (ii) a stereoselective allylation with allyltributylstannane, and (iii) an enantioselective Grignard addition to an α-oxygenated aldehyde.",10.1055/s-0030-1260014,2011-04-20,0.6553631260922892
Organic Letters,"Synthesis of 3-Substituted 2-Fluoro- and 2,2-Difluoroaziridines","A new route for the synthesis of stable 3-alkyl- and 3-aryl-2(,2)-(di)fluoroaziridines was developed by hydride reduction of novel alpha-bromo- and alpha-chloro-alpha(,alpha)-(di)fluoroketimines and subsequent ring closure of beta-fluorinated beta-chloro- and beta-bromoamines. This is the first report on the synthesis of 2,2-difluoroaziridines sensu stricto.",10.1021/ol071127x,2007-06-29,0.655356999801112
Organic Process Research & Development,"A Concise Synthesis of Racemic 1-(6,7-Dimethoxy-2-naphthyl)-1-(1 <i>H</i> -imidazol-4-yl)-2-methylpropan-1-ol for a Potent C <sub>17</sub> , <sub>20</sub> -Lyase Inhibitor","The development of a practical and scaleable synthesis of 1-(6,7-dimethoxy-2-naphthyl)-1-(1 H -imidazol-4-yl)-2-methylpropan-1-ol ( 2 ) is described. Racemate 2 was synthesized from commercially available 4(5)-imidazolecarboxyaldehyde ( 7 ) in three steps excluding chromatography. 4(5)-Cyanoimidazole ( 10 ) was prepared from 7 in good yield in a one-pot reaction. A Grignard reaction of cyanoimidazole 10 with isopropylmagnesium bromide followed by the addition of aqueous sulfuric acid formed acylimidazole 9 . The final racemate 2 was obtained by the direct Grignard reaction of acylimidazole 9 without N-protection. This process was accomplished efficiently to produce 2 in 70% overall yield from 7 in a large-scale synthesis.",10.1021/op060171+,2007-01-20,0.6553069547568018
Tetrahedron,An Efficient Synthesis of Large Ring Acetylenes,,10.1016/00404-0399(50)11469-,1995-08-07,0.6553059924535646
Tetrahedron,An efficient synthesis of large ring acetylenes,,10.1016/0040-4039(95)01146-9,1995-08-01,0.6553059924535646
Tetrahedron,"Laboratory and practical synthesis of Suvorexant, a selective dual orexin receptor antagonist",,10.1016/j.tetlet.2014.08.086,2014-08-28,0.6552933040540418
Organic Process Research & Development,"Development and Scale-Up of an Enabling Synthetic Route to <b>KTX-005</b>, a Muscarinic Acetylcholine Receptor Agonist for the Potential Treatment of Schizophrenia","Development and optimization of phase-appropriate synthetic technologies to prepare KTX-005, a potent muscarinic acetylcholine receptor agonist, are described in this article. The modular strategy involves three building blocks: commercially available materials dichlorothiadiazole ( 21 ), butanethiol ( 22 ), and custom-synthesized azabicyclo derivative ( 18 ). The highlight of the enabling synthetic strategy toward KTX-005 is a unique thiadiazole ring opening/closing sequence to facilitate both dichlorothiadiazole desymmetrization with butanethiol as well as functionalization of the azabicyclo ring derivative 18 .",10.1021/acs.oprd.4c00531,2025-02-06,0.6552780397861327
Tetrahedron,"A new synthesis of 2-methyl-3-hydroxypyridine-4,5-dicarboxaldehyde",,10.1016/s0040-4039(00)76345-3,1968-01-01,0.6552549200717637
Journal of the American Chemical Society,Total Synthesis of the Securinega Alkaloid (−)-Secu’amamine A,"The first enantioselective total synthesis of the rearranged Securinega alkaloid (-)-secu'amamine A is reported starting from D-proline as the source of absolute chirality. The synthesis requires 15 steps starting from D-proline-derived N-trityl aldehyde 11 and proceeds in approximately 9% overall yield. Key steps include a stereoselective conjugate addition of pyrrolidino enedione 19 to afford indolizidine 24 as the major product and cyclization/lactonization of diketoester 25 to produce tetracycle 26. In addition, 1H NMR NOE studies and X-ray analysis on the synthetic alkaloid have established that the indolizidine moiety is trans-fused.",10.1021/ja802700z,2008-05-21,0.6552475819469499
European Journal of Organic Chemistry,Enantioselective Total Synthesis of (–)‐Siphonodictyal B and (+)‐8‐<i>epi</i>‐Siphonodictyal B with Phosphatidylinositol 3‐Kinase α (PI3Kα) Inhibitory Activity,"The biologically interesting marine meroterpenoids (–)‐siphonodictyal B and (+)‐8‐ epi ‐siphonodictyal B were efficiently synthesized in 29–40 % overall yield in a longest linear sequence of 11 steps, starting from commercially available (+)‐sclareolide. The synthesis involved the following crucial steps: (i) stereodivergent hydrogenation of a homoallylic decalin alcohol to install the requisite C8 stereogenic centre present in the decalin fragments; (ii) coupling of the decalin fragments with an aromatic moiety to assemble the desired carbon skeletons; and (iii) deprotection from multiple O ‐protective groups on the aromatic ring to complete the project synthesis. Both (–)‐siphonodictyal B and (+)‐8‐ epi ‐siphonodictyal B showed PI3Kα inhibitory activity, with potencies comparable to that of liphagal, a naturally occurring PI3Kα inhibitor. New structure–activity relationships for this class of marine meroterpenoids were also revealed.",10.1002/ejoc.201600949,2016-09-19,0.6552443364375377
Angewandte Chemie International Edition,A Concise Enantioselective Total Synthesis of (−)‐Deoxoapodine,"We have established a highly convergent 10-step route for the total synthesis of (-)-deoxoapodine, which is a hexacyclic aspidosperma alkaloid. The quaternary C5 center of the characteristic tetrahydrofuran ring was constructed by a chiral-phosphoric-acid-catalyzed enantioselective bromocycloetherification in a 5-endo fashion and subsequent allylation by using the Keck protocol. Construction of the aspidosperma skeleton features the formation of a nine-membered lactam by a catalytic C-H palladation/alkylation cascade at the indole 2-position and an iron-catalyzed oxidative transannular reaction at a late-stage of the synthesis.",10.1002/anie.202010759,2020-09-27,0.6552353093843688
Journal of Organic Chemistry,A Total Synthesis of Nannochelin A. A Short Route to Optically Active <i>N</i><sup>ω</sup>-Hydroxy-α-amino Acid Derivatives,"The total synthesis of nannochelin A, a lysine-basd cinnamoyl hydroxamate produced by Nannocystis exedens, is described. The key transformation involves construction of the N ε -cinnamoyl- N ε -hydroxy- l -lysine methyl ester fragment by partial reduction of the lactam carbonyl of 6 derived from l -lysine, oximation of this aldehyde equivalent compound 8 with O -[2-(trimethylsilyl)ethyl]hydroxylamine, and reduction of the oxime 10, followed by N-acylation prior to coupling with the external carbonyls of citric acid. This methodology will be applicable to synthesis of other hydroxamate-containing siderophores bearing hydrogenolyzable groups in the molecule.",10.1021/jo961458f,1996-01-01,0.655214740790256
Organic Letters,Synthetic Approach to the Core Structure of Oleandrin and Related Cardiac Glycosides with Highly Functionalized Ring D,"The first synthetic approach to the core structure of cardiac glycoside oleandrin exhibiting a potent cytotoxic activity, starting from a common androstane derivative, has been accomplished. The synthesis is focused on stereoselective transformations in the densely substituted and sterically shielded five-membered ring (steroid ring D). The developed synthesis paves a route to the synthesis of related bufadienolides, i.e., constituents of traditional drug Ch'an Su, bufotalin, and cinobufagin.",10.1021/acs.orglett.6b03157,2016-11-22,0.6551861922949759
Tetrahedron,Copper catalyzed aminolysis of bromoallenes as a new efficient route to propargylamines,,10.1016/0040-4039(91)80138-v,1991-12-01,0.655178591190427
Synlett,"A Sydnone-Based Route to Indazolo[2,3-a]quinoxaline Derivatives","Abstract A new synthetic route to indazolo[2,3-a]quinoxaline derivatives is described. The strategy is based on the 1,3-dipolar cycloaddition of arynes to quinoxaline–sydnone derivatives as a key step. The polyaromatic sydnones were prepared through a copper-promoted intramolecular cyclization of the C-4 position of sydnones on imines.",10.1055/a-1774-7618,2022-02-17,0.6551698624019661
Tetrahedron,"A new, highly efficient synthesis of conjugated nitrocycloalkenes",,10.1016/s0040-4039(00)77291-1,1994-08-01,0.6550992329064145
Organic Letters,Toward the Total Synthesis of Hygrocin B and Divergolide C: Construction of the Naphthoquinone–Azepinone Core,"A highly regioselective Diels-Alder approach toward the bioactive natural products hygrocin B and divergolide C is presented. The route uses an unusual benzoquinone-azepinone dienophile prepared in 8 steps from ethyl 8-methoxy-1-naphthoate, by a route which includes, as key steps, a Birch alkylation and a Beckmann rearrangement of a tetralone oxime, both of which are demonstrated on multigram scale. The naphthoquinone-azepinone core is suitably functionalized for addition of the ansa-chain, found in the natural products.",10.1021/ol5003847,2014-03-25,0.6550636788891916
Tetrahedron,Asymmetric synthesis XV : enantiospecific synthesis of (+) and (−) isonitramines from a common chiral intermediate,,10.1016/0040-4039(88)85149-9,1988-01-01,0.6550489696778369
Organic Letters,"Efficient Asymmetric Total Syntheses of Cryptocarya Triacetate, Cryptocaryolone, and Cryptocaryolone Diacetate","Concise and efficient asymmetric total syntheses of three substituted alpha-pyrone-type natural products have been accomplished via 7-9 steps from 5b in high overall yields, which involve linchpin coupling, ring-closing metathesis, and a tandem sequence of deacetylation and intramolecular oxa-Michael addition as the key steps.",10.1021/ol901024t,2009-06-19,0.6550472588788544
Synthesis,Divergent Synthetic Strategy To Access the Polyketide Subunits of Aurilides: Synthesis of the Southern Fragment of Lagunamides D and D′,"Abstract We report a flexible stereocontrolled synthetic route to the southern fragment of lagunamides D and D′, two cytotoxic cyclodepsipeptides of the aurilide family. Key steps in the route include an anti-aldol Abiko–Masamune reaction and a Horner–Wadsworth–Emmons (HWE) olefination. The key element of our synthetic strategy was the use of a pivotal intermediate which allows the introduction a side chain that differentiates the polyketide structure of the members of the family. Thus, to illustrate the synthetic potential of our strategy, we have also prepared four different advanced polyketide precursors.",10.1055/a-2500-6392,2024-12-11,0.6550365459784505
Synthesis,"A Novel Approach to Both the Enantiomers of Potent Glycosidase Inhibitor Isofagomine via PET-Promoted Cyclization of 1-[Benzyl(trimethylsilyl-methyl)amino]-1,4,5-trideoxy-2,3-<b><i>O</i></b>-(1-methylethylidene)-<b><i>threo</i></b>-pent-4-ynitol","The cyclization of PET-generated α-trimethylsilylmethylamine radical cation to a tethered acetylene moiety has been exploited to solve the problem of the generation of an aminomethyl group next to a stereocenter in the synthesis of 1-N-iminosugar type glycosidase inhibitors. Its success is demonstrated by the synthesis of (+)- as well as (-)-isofagomine, an extremely potent β-glucosidase inhibitor of the 1-N-iminosugar class.",10.1055/s-2001-15063,2002-07-26,0.655003152050808
Tetrahedron,"Synthesis of a benzo[b]-1,5-naphthyridine derivative as a potential constrained NK1 receptor antagonist",,10.1016/s0040-4039(00)78224-4,1994-08-01,0.6549810315349612
Tetrahedron,"Stereospecific route for the synthesis of 1,5-lactams : Synthesis of (2S,3S,4R,5R)-methyl-3,4,5-triphenylmethylenoxy-6-oxo-piperidine-2-carboxylate",,10.1016/s0040-4039(00)76990-5,1994-07-01,0.6549746505742162
Organic Process Research & Development,"Efficient, Protecting Group Free Kilogram-Scale Synthesis of the JAK1 Inhibitor GDC-4379","The development of an improved kilogram-scale synthesis of the JAK1 inhibitor GDC-4379 for the treatment of asthma is described. The new process is highlighted by a step-economical construction of a 3-substituted-4-aminopyrazole employing a telescoped oximation and hydrazine condensation of a 1,3-dielectrophile to generate nitrosopyrazole and a novel copper-catalyzed NaBH 4 reduction of the nitroso group. The endgame process features an amidation of aminopyrazole with acid chloride under Schotten–Baumann conditions to provide access to the penultimate intermediate. A selective N-1 alkylation of the pyrazole moiety was accomplished under phase-transfer conditions, which delivered GDC-4379 with a defined particle-size distribution suitable for micronization after recrystallization and wet milling.",10.1021/acs.oprd.1c00302,2021-11-11,0.6549722554413991
Organic Letters,Synthesis of <scp>l</scp>-Kedarosamine in Protected Form and Its Efficient Incorporation into an Advanced Intermediate to Kedarcidin Chromophore,"An efficient route to the complex L-kedarosamine alpha-glycosidic ether 2, a synthetic precursor to kedarcidin chromophore, is described. Central to the route, which is suitable for the preparation of multigram amounts of material, is a short synthetic sequence from D-threonine to protected L-kedarosamine derivatives and methodology for their alpha-selective coupling with appropriate hydroxyl acceptors.",10.1021/ol070450x,2007-04-18,0.6548987224337167
Organic Process Research & Development,Improved Synthesis of a Macrocyclic Peptide-Like C5aR Antagonist for Intravenous Applications,"A multigram scale synthetic procedure for the preparation of a complex and polar macrocyclic peptidic C5aR antagonist is described. The route was developed through improvements to an initial small-scale research synthesis and hinged on optimized solid-phase peptide synthesis featuring an early side chain decoration, a highly efficient off-resin macrolactamization, and global deprotection steps. These improvements resulted in a reduction in off-resin peptide manipulations and ultimately to a 6-fold increase in overall yield from 2-chlorotrityl-bound intermediate SP-7c .",10.1021/acs.oprd.3c00202,2023-10-19,0.6548892951803615
Organic Letters,Total Synthesis of Aplyronine C,A highly stereocontrolled total synthesis of the cytotoxic marine macrolide aplyronine C is described. The route exploits aldol methodology to install the requisite stereochemistry and features a crucial boron-mediated aldol coupling of an N-vinylformamide-bearing methyl ketone with a macrocyclic aldehyde to introduce the full side chain. The synthesis of two novel C21-C34 side chain analogs is also reported.,10.1021/ol401327r,2013-06-03,0.6548862882775922
Synlett,"First Asymmetric Synthesis of New Diarylheptanoids, Renealtin A and B, with a Tetrahydrofuran Ring","An efficient and convenient process is described for the first preparation of a new diarylheptanoid, renealtin A, isolated from the seeds of the Brazilian medicinal plant Renealmia exaltata. The key trisubstituted tetrahydrofuran ring was constructed through Lewis acid mediated stereoselective allylation of the lactol derivative by featuring the elaboration of the functionalized homochiral lactone derived from l-tartaric acid. The synthesis of the other ­minor stereoisomer, renealtin B, was also established.",10.1055/s-2006-948168,2006-08-01,0.6548795343916228
Organic Letters,Total Synthesis of (−)-Huperzine A,The total synthesis of (-)-huperzine A was accomplished in 23 steps from a commercially available anhydride. Our synthetic route features a facile construction of the bicyclo[3.3.1] skeleton equipped with proper functionalities to introduce the remaining substructures.,10.1021/ol9022408,2009-10-29,0.6548697943217026
Organic Letters,Total Synthesisof Honokiol via Oxidative Phenol Coupling,"Herein we disclose the total synthesis of honokiol in six steps in an overall yield of 66%. Two distinct routes were explored, with the key steps being highly efficient and selective cross-couplings of commercially available phenols to construct the main biphenolic backbone. The routes employ inexpensive reagents and are scalable, high-yielding processes. The experimental procedures are reported in the conventional narrative format and two machine-readable formats.",10.1021/acs.orglett.5c03477,2025-10-09,0.6548673801161632
Journal of Organic Chemistry,Concise Total Synthesis of (−)-Codeine,"Codeine and morphine are among the few natural products that are used directly as drugs for medical treatment. However, the availability of these is widely dependent on natural resources. Herein, we report an efficient enantioselective seven-step synthesis of (-)-codeine starting from simpler starting materials. The key steps involve microwave-assisted intramolecular cascade double heck cyclization to access the ABCE ring of opium alkaloids with the required stereocenters in one pot. A photoinduced intramolecular hydroamination of carboxamide forms the D ring and completes the pentacyclic core of the morphinans. Following that, an oxidation followed by global reduction leads to the formation of (-)-codeine. Our synthesis relies on simple and classical reactions to address the opium alkaloids and will serve as an efficient route to access the other morphinans.",10.1021/acs.joc.4c01452,2024-08-21,0.6548546154133568
Organic Letters,Pd-Catalyzed Carbonylative Lactamization:  A Novel Synthetic Approach to FR900482,"An asymmetric synthesis of the benzazocine core of FR900482 has been achieved in 15 steps from 3,5-dinitro-p-toluic acid. Key features of the synthesis include an enantioselective N-methylephedrine-mediated zinc acetylide addition to a highly enolizable arylacetaldehyde and a novel Pd-catalyzed carbonylative lactamization to form an eight-membered ring. [reaction--see text]",10.1021/ol049583y,2004-04-24,0.6548523344594619
Organic Letters,Synthesis of Eudistomin C and E: Improved Preparation of the Indole Unit,"An improved synthesis of the indole unit, a key intermediate for eudistomin C, was established utilizing Makosza's indole synthesis. A concise total synthesis of eudistomin E was achieved on the basis of the improved synthesis.",10.1021/ol800527p,2008-05-23,0.6548336133761394
Journal of Organic Chemistry,"Synthesis of (−)-9,10-<i>epi</i>-Stemoamide","An efficient synthesis of (-)-9,10-epi-stemoamide has been accomplished in nine steps and 13% overall yield. The synthesis features a lithium hydroxide-promoted fragmentation and an intramolecular 7-exo-trig radical cyclization.",10.1021/jo049083i,2004-10-01,0.6548186698998317
Journal of the American Chemical Society,Enantioselective Total Syntheses of Citrinadins A and B. Stereochemical Revision of Their Assigned Structures,"The concise, enantioselective total syntheses of (-)-citrinadin A and (+)-citrinadin B in a total of only 20 and 21 steps, respectively, from commercially available starting materials are described. Our strategy, which minimizes refunctionalization and protection/deprotection operations, features the highly diastereoselective, vinylogous Mannich addition of a dienolate to a chiral pyridinium salt to set the first chiral center. The absolute stereochemistry of this key center was then relayed by a sequence of substrate-controlled reactions, including a highly stereoselective epoxidation/ring opening sequence and an oxidative rearrangement of an indole to furnish a spirooxindole to establish the remaining stereocenters in the pentacyclic core of the citrinadins. An early stage intermediate in the synthesis of (-)-citrinadin A was deoxygenated to generate a dehydroxy compound that was elaborated into (+)-citrinadin B by a sequence of reaction identical to those used to prepare (-)-citrinadin A. These concise syntheses of (-)-citrinadin A and (+)-citrinadin B led to a revision of their stereochemical structures.",10.1021/ja5074646,2014-09-29,0.6548148080833704
Organic Process Research & Development,"An Efficient Scalable Route for the Synthesis of Enantiomerically Pure <i>tert</i>-Butyl-(1<i>R</i>,4<i>S</i>,6<i>R</i>)-4-(hydroxymethyl)-3-azabicyclo[4.1.0]heptane-3-carboxylate","An efficient scalable route to synthesize the enantiomerically pure tert -butyl-(1 R,4 S,6 R )-4-(hydroxymethyl)-3-azabicyclo[4.1.0]heptane-3-carboxylate is described. Compared to the original routes, significant improvements were made by using an innovative approach starting from commercially available chiral lactone. In this approach, one of the key steps described is an elegant epimerization/hydrolysis of the undesired diastereoisomer avoiding tedious purification. The chemistry has been scaled up to produce kilogram amounts of tert -butyl-(1 R,4 S,6 R )-4-(hydroxymethyl)-3-azabicyclo[4.1.0]heptane-3-carboxylate in 43% yield over nine chemical transformations.",10.1021/op100164v,2010-08-25,0.6547805512007937
Journal of Organic Chemistry,Asymmetric Synthesis of 6′-Hydroxyarenarol: The Proposed Biosynthetic Precursor to Popolohuanone E,"The first synthesis of (+)-6'-hydroxyarenarol 3, the proposed biogenetic precursor to popolohuanone E (1), is described. An enantioselective route to key iodide intermediate 12 has been developed allowing the asymmetric synthesis of the known cis-decalin 22. Conditions which allow the removal of the methyl ether protecting groups on the hydroxyarene leaving the exocyclic methylene moiety in tact have also been developed to complete this synthesis.",10.1021/jo801404u,2008-09-18,0.6547752804751515
Journal of Organic Chemistry,First Total Synthesis of Cyrmenin B<sub>1</sub>,"A short and efficient synthesis of cyrmenin B(1), an antifungal metabolite of myxobacteria Cystobacter armeniaca and Archangium gephyra, is described. The crucial steps of the synthesis included the formation of the dehydroalanine moiety from the corresponding serine acetate and the formation of the beta-methoxyacrylate system via trimethylsilyldiazomethane methylation of the corresponding beta-hydroxy enamide.",10.1021/jo802209m,2008-11-26,0.6547728485183033
Organic Letters,"Short and Scalable Total Synthesis of Myrioneuron Alkaloids (±)-α,β-Myrifabral A and B","The first total synthesis of the Myrioneuron alkaloids (±)-α,β-myrifabral A and B has been accomplished in only four steps from conveniently available starting materials. This short synthesis relied on the use of a key tandem Mannich/amidation reaction to rapidly construct the core framework and two carbon stereocenters. The synthetic route allows for large scale preparation of these promising natural products against the hepatitis C virus (HCV).",10.1021/acs.orglett.6b00005,2016-02-05,0.6547561569047744
Organic Letters,A New Total Synthesis of the Zinc Matrixmetalloproteinase Inhibitor Ageladine A Featuring a Biogenetically Patterned 6π-2-Azatriene Electrocyclization,[reaction: see text] A convergent second generation total synthesis of the heterocyclic marine sponge metabolite ageladine A has been achieved by using a biomimetically inspired 6pi-2-azatriene electrocyclization as the key step for formation of the imidazolopyridine moiety.,10.1021/ol063038a,2007-01-30,0.6547512137330135
Organic Process Research & Development,Concise and Efficient Synthesis of [6]-Paradol,"An efficient synthesis of [6]-paradol ( 1 ) has been performed in four steps with a 72.0% overall yield. The present method highlights commercially available materials, convenient isolation with multiple crystallization without involving column chromatography, and a high-purity product (more than 99.2%), and it is amenable to large-scale synthesis.",10.1021/acs.oprd.0c00553,2021-05-20,0.6547472668737303
Tetrahedron,Synthesis of novel polyhydroxylated quinolizidines: Ring expanded analogs of glycosidase inhibitory indolizidines,,10.1016/s0040-4039(00)61395-3,1993-12-01,0.6547348789171488
Tetrahedron,"Synthesis of a novel tetracyclic azaindolo[2,1-c][1,4]benzoxazine ring system",,10.1016/j.tetlet.2011.02.020,2011-02-10,0.6547348789171488
Tetrahedron,The synthesis of novel bridged a ring steroids,,10.1016/s0040-4039(00)61823-3,1987-01-01,0.6547348789171488
Tetrahedron,A novel synthesis of the carbapen-2-em ring system,,10.1016/s0040-4039(00)93616-5,1980-01-01,0.6547348789171488
Journal of Organic Chemistry,Synthesis of Valsartan via Decarboxylative Biaryl Coupling,"An efficient synthesis of the angiotensin II inhibitor valsartan (Diovan) is presented. Two routes were evaluated, both making use of an advanced version of our decarboxylative coupling for the construction of the biaryl moiety. Thus, in the presence of a catalyst system consisting of copper(II) oxide, 1,10-phenanthroline, and palladium(II) bromide, 2-cyanocarboxylic acid was coupled with 1-bromo(4-dimethoxymethyl)benzene in 80% yield and with 4-bromotoluene in 71% yield. The valsartan synthesis using 1-bromo(4-dimethoxymethyl)benzene was completed in four steps overall with a total yield of 39%, via a novel route that presents substantial economical and ecological advantages over the literature process, as it is more concise and stoichiometric amounts of expensive organometallic reagents are avoided.",10.1021/jo701391q,2007-08-23,0.6547315476109903
Synthesis,"Efficient Asymmetric Synthesis of (2R,3R)-3-{(1R)-1-[tert-Butyl(dimethyl)-siloxy]ethyl}-4-oxoazetidin-2-yl Acetate","(2R,3R)-3-{(1R)-1-[tert-Butyl(dimethyl)siloxy]ethyl}-4-oxoazetidin-2-yl acetate was efficiently prepared from l-ascorbic acid. The key steps were the a highly diastereoselective [2 + 2] cycloaddition of diketene with an (S)-glyceraldehyde-derived ald­imine to give the ketone, stereoselective titanium tetrachloride mediated asymmetric reduction to give the corrsponding S-configured alcohol, and Mitsunobu inversion of the latter to give the desired R-configured alcohol.",10.1055/s-0030-1258407,2011-01-17,0.6547174198587337
Journal of the American Chemical Society,Enantioselective Total Synthesis of (−)-Citrinadin A and Revision of Its Stereochemical Structure,"The first enantioselective total synthesis of (-)-citrinadin A has been accomplished in 20 steps from commercially available materials via an approach that minimizes refunctionalization and protection/deprotection operations. The cornerstone of this synthesis features an asymmetric vinylogous Mannich addition of a dienolate to a chiral pyridinium salt to set the initial chiral center. A sequence of substrate-controlled reactions, including a highly stereoselective epoxidation/ring-opening sequence and an oxidative rearrangement of an indole to furnish a spirooxindole, are then used to establish the remaining stereocenters in the pentacyclic core of (-)-citrinadin A. The successful synthesis of citrinadin A led to a revision of the stereochemical structure of the core substructure of the citrinadins.",10.1021/ja405547f,2013-07-09,0.6547132675488448
Tetrahedron,Facile synthesis of the glucosylceramide synthase inhibitor GZ667161,,10.1016/j.tetlet.2020.152352,2020-08-16,0.654653886758915
Organic Letters,Convergent Synthesis and Discovery of a Natural Product-Inspired Paralog-Selective Hsp90 Inhibitor,"A convergent synthesis of benzoquinone ansamycin analogs is described that proceeds by a sequence of metallacycle-mediated alkyne-alkyne coupling, followed by site- and stereoselective dihydroxylation and global carbamate formation. These studies have led to (1) validation of alkyne-alkyne coupling to produce geldanamycin analogs that lack the problematic quinone, (2) the discovery that C6-C7 bis-carbamate functionality is compatible with Hsp90 inhibition, and (3) the identification of 1 as a nonquinone geldanamycin-inspired paralog-selective Hsp90 inhibitor.",10.1021/ol2019828,2011-08-25,0.6546506835494696
Synlett,Stereocontrolled Synthesisof the Tetracyclic Core Framework of (-)-Lemonomycin,"In a convergent approach, an advanced intermediate (2) in a projected total synthesis of the alkaloid (-)-lemonomycin (1) was prepared from readily available starting materials. The key transformations were a Pictet-Spengler cyclization, a Strecker-type amino alkylation, and an N-acyliminium cyclization.",10.1055/s-2008-1078273,2008-08-22,0.6546371022202211
Journal of Organic Chemistry,Correction to “Convergent and Scalable Synthesis of ABCDE-Ring Fragment of Caribbean Ciguatoxin C-CTX-1”,,10.1021/acs.joc.5c02464,2025-11-03,0.6546103385882233
Journal of Organic Chemistry,"Stereoselective Synthesis of MLN4924, an Inhibitor of NEDD8-Activating Enzyme","MLN4924 (1), which is in clinical trials as an anticancer agent, was stereoselectively synthesized from d-ribose via a route involving stereoselective reduction, regioselective cleavage of an isopropylidene moiety, and selective displacement of a cyclic sulfate moiety as key steps.",10.1021/jo2001897,2011-03-21,0.6546064511062969
Angewandte Chemie International Edition,A Concise Synthesis of (−)‐Oseltamivir,"Tackling the supply problem: A short and efficient synthesis of (−)-oseltamivir has been developed which requires eight steps from commercially available starting material and proceeds with an overall yield of 30 %. Key transformations include a novel palladium-catalyzed asymmetric allylic alkylation reaction (Pd-AAA, see scheme) as well as a chemo-, regio-, and stereoselective aziridination reaction. Phth=phthaloyl.",10.1002/anie.200800282,2008-04-10,0.6546036768380464
Tetrahedron,"Total synthesis of flutimide, a novel endonuclease inhibitor of influenza virus",,10.1016/0040-4039(95)00214-w,1995-03-01,0.6545971598405429
Journal of Organic Chemistry,Synthesis of the KLMN Fragment of Gymnocin-A from the FGH Fragment,"An improved route for the synthesis of the KLMN fragment of gymnocin-A was developed through the oxiranyl anion coupling of the FGH fragment with a chiral C 3 epoxy sulfone, followed by 6-endo cyclization. This straightforward approach reduced the number of synthetic steps by 14 compared with a previous route using alternative building blocks.",10.1021/acs.joc.7b00232,2017-03-09,0.6545656150679432
Tetrahedron,Synthesis of the topoisomerase II inhibitor BE 10988,,10.1016/s0040-4039(00)91982-8,1993-03-01,0.6545365284345397
Synlett,An Enantioselective Total Synthetic Approach to (+)-Heptemerone G and (+)-Guanacastepene A from 2-Furyl Methyl Carbinol,An enantioselective synthesis of the key bicyclic building block for (+)-heptemerone G and (+)-guanacastepene A construction has been accomplished. 2-Furyl methyl carbinol was used as the starting material and ( S )-4-hydroxy-2-methylcyclopent-2-en-1-one as the primal optically active intermediate.,10.1055/s-0033-1338857,2013-06-06,0.6545328402272765
Organic Letters,"Total Synthesis of Waltherione F, a Nonrutaceous 3-Methoxy-4-quinolone, Isolated from <i>Waltheria indica</i> L. F.",Waltherione F was totally synthesized in seven steps and 31% overall yield from 2-nitro-3-methylanisole without the use of protecting groups. Key steps in the sequence were a Suzuki-Miyaura coupling to attach the n-octyl chain and a microwave-promoted cyclization of an acetonyl anthranilate to give the heterocyclic core whose 3-OH was O-methylated.,10.1021/acs.orglett.8b02221,2018-08-06,0.654529323228922
Journal of Organic Chemistry,"(1<i>S</i>)-1-[(4<i>R</i>)-2,2-Dimethyl-1,3-dioxolan-4-yl]-2-hydroxyethylammonium Benzoate, A Versatile Building Block for Chiral 2-Aminoalkanols:  Concise Synthesis and Application to Nelfinavir, a Potent HIV-Protease Inhibitor","A concise synthesis of a versatile chiral C4 building block for 2-aminoalkanols, (1S)-1-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2-hydroxyethylammo nium benzoate (1a), was described. 1 (1a and its enantiomer 1b) acted as four stereoisomers of optically active 2-amino-1,3,4-butanetriol. The versatility of 1 was demonstrated by its application to the practical synthesis of nelfinavir (2), a potent HIV-protease inhibitor, as well as by the stereospecific synthesis of three diastereomers of 2.",10.1021/jo991793e,2000-03-01,0.6545221138527512
Organic Process Research & Development,Process Development and Scale-Up of the Novel β-Lactamase Inhibitor WCK 6395,"The initial process development of the novel β-lactamase inhibitor WCK 6395 is described. All key intermediates were readily isolated by either crystallization or precipitation to eliminate related impurities. Seven possible process-related impurities were hypothesized, and initial control strategies were implemented. Additionally, process parameters were identified and improved to decrease or circumvent these impurities. The parameters of each step were optimized through prior knowledge and experimentation to improve yield and desired quality of WCK 6395 to support toxicological studies. The improved process effectively reduced the use of hazardous reagents, was robust on the kilogram scale, demonstrated at the pilot scale, and subsequently served as the basis for commercial route development.",10.1021/acs.oprd.2c00349,2023-03-03,0.6545172922257034
Organic Process Research & Development,"Scale-Up of a Chemo-Biocatalytic Route to (2<i>R</i>,4<i>R</i>)- and (2<i>S</i>,4<i>S</i>)-Monatin","Monatin, a natural sweetener, refers to a collection of four isomers of 2-((1 H -indol-3-yl)methyl)-4-amino-2-hydroxypentanedioic acid. A chemo-biocatalytic approach to kilogram quantities of enantiopure 2 S,4 S -monatin and 2 R,4 R -monatin from indole is described. Key steps in the process include a (2 + 3) cycloaddition reaction followed by nickel-catalysed reduction to construct the monatin backbone, and a highly selective enzyme resolution of the 2 S,4 S - and 2 R,4 R -monatin diastereomeric pair to afford each enantiomer in 99% ee.",10.1021/op1001947,2010-12-02,0.6545148545240292
Journal of Organic Chemistry,Synthesis and Stereochemistry of the Antitumor Diterpenoid (+)-Zerumin B,"Starting from commercially available (+)-sclareolide, the first synthesis of zerumin B was achieved by a concise, highly efficient pathway featuring stereoselective addition of a new silyloxyfuryltitanium reagent to an aldehyde intermediate and silyloxyfuran oxyfunctionalization as key steps. The synthesis established the relative and absolute configuration of zerumin B along with its identity with a purportedly new diterpenoid isolated from the plant Renealmia alpinia.",10.1021/jo0610154,2006-07-18,0.6545091605193745
Journal of the American Chemical Society,An Expedient Asymmetric Synthesis of Platencin,"A short and efficient synthesis of enone 3, a key intermediate in the total synthesis of platencin (2), based on an intramolecular Diels-Alder reaction is described.",10.1021/ja804588r,2008-07-30,0.6545043017053551
Organic Process Research & Development,"Route Optimization of the Non-covalent Modulator of Hemoglobin PF-07059013 for the Treatment of Sickle Cell Disease, Part I: From Discovery Synthesis to First Kilogram-Scale Manufacture","The scalable route to PF-07059013 ( 3 ), a non-covalent modulator of hemoglobin for the treatment of sickle cell disease, is discussed. Optimization of the discovery route is presented, examining bond connections, late-stage Buchwald–Hartwig C–O coupling, and palladium content reduction strategies. The first process chemistry route to deliver 11 kg of the final API is also discussed.",10.1021/acs.oprd.2c00351,2023-02-22,0.6544955227561191
Organic Process Research & Development,A Novel Process for Antimalarial Drug Pyronaridine Tetraphosphate,"A novel process for preparation of pyronaridine tetraphosphate, an antimalarial drug substance, is reported. The overall yields are 54% and >99.8% (including five chemical steps). Formation and control of possible impurities are also described.",10.1021/op400357f,2014-01-28,0.6544857465447858
Journal of Organic Chemistry,Studies toward the Total Synthesis of Nominine,"The construction of the hetisane group of alkaloids, of which the extensively bridged nominine 17 is the simplest member, poses the ultimate challenge for those interested in the synthesis of the C20 diterpene alkaloids. We describe the synthesis of an advanced intermediate toward this goal. The key steps include reductive acylation, reductive deoxygenation, Birch reduction, and an intramolecular Lewis acid-catalyzed 1,6-addition of a carbamate to a dienone.",10.1021/jo701995u,2007-11-21,0.654448436071799
Tetrahedron,Stereospecific synthesis of a biologically active dehydro derivative of the C18-juvenile hormone of cecropia. New routes to a key C12-intermediate,,10.1016/s0040-4039(01)87471-2,1971-01-01,0.6544460034209435
European Journal of Organic Chemistry,A New Synthetic Approach to High‐Purity (15<i>R</i>)‐Latanoprost,"Abstract This paper describes a new synthesis of latanoprost ( 1 ) that afforded high purity latanoprost in 16.9 % overall yield in eight synthetic steps from sulfone 4 . The “α chain” in a derivative of the (–)‐“Corey lactone” was elongated first, followed by the attachment of a novel, enantiomerically pure “ω chain” synthon. This ensured the absence of the undesired (15 S )‐ 1 diastereomer in the synthesized prostaglandin. The crystalline nature of the novel sulfone 4 facilitated its purification. A variation of the new synthesis of latanoprost is described, where the laboratory‐scale synthesis was further adapted to a hundred‐gram scale. In the course of the present synthesis, a new prostaglandin sulfone intermediate, 21 , which may find application in the synthesis of diverse prostaglandin analogs, was introduced. A practical synthesis of novel, enantiomerically pure “ω chain” synthons 15 , 16 , and 17 has also been carried out, employing diol 12 , which was obtained from derivatives of the D ‐mannitol chiral pool. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2007)",10.1002/ejoc.200600749,2006-11-23,0.6544123202790947
Organic Process Research & Development,Development of Large-Scale Synthesis using a Palladium-Catalyzed Cross-Coupling Reaction for an Isoquinolone Derivative as a Potent DPP-4 Inhibitor,"An efficient large-scale synthesis of a novel DPP-4 inhibitor 1, an isoquinolone derivative bearing an aminomethyl group at the 3-position and carbamoylmethoxy group at the 6-position, is described. We have developed an effective and convenient synthetic method utilizing a key intermediate possessing a cyano group at the 3-position and a halogen atom at the 6-position. The key reaction, the insertion of an oxygen atom at the 6-position of isoquinolone was achieved by a cross-coupling reaction using 6-bromoisoquinolone and sodium tert -butoxide ( t BuONa) in the presence of Pd(OAc) 2 and rac -BINAP as a catalyst to afford 6- tert -butoxyisoquinolone in good yield. The cyano group at the 3-position was hydrogenated in the presence of Raney nickel to give the aminomethyl moiety of compound 1 . The synthetic route has been successfully applied to multikilogram-scale preparations in good yield and high quality.",10.1021/op5000072,2014-02-17,0.654399185234655
Synlett,Efficient Synthesis of Polycycles by Electrocyclizations of Substituted Trihydroxybenzenes: Synthesis of Rubranine and Deoxybruceol,"A new synthetic route for biologically interesting polycycles with a citran and a cyclol nucleus was developed starting from several substituted trihydroxybenzenes. This methodology was applied successfully to the synthesis of two natural products, rubranine and deoxybruceol.",10.1055/s-2007-985562,2007-07-24,0.654395330079319
Tetrahedron,Synthesis of puleganic amides via a catalytically efficient two-step approach,,10.1016/j.tetlet.2018.06.067,2018-06-30,0.6543824418532623
Angewandte Chemie International Edition,Scalable Total Synthesis of (−)‐Berkelic Acid by Using a Protecting‐Group‐Free Strategy,Supply chain: the polycyclic core of (-)-berkelic acid (1) was constructed in just one step from very simple starting materials. The total synthesis of 1 involves a seven-step linear sequence. Protection/deprotection steps were avoided and all but the last step were performed on a gram scale. This synthesis could solve the supply problem associated with the exhaustion of the natural source.,10.1002/anie.201109076,2012-04-04,0.6543745677215671
Journal of Organic Chemistry,"Total Synthesis of (±)-Flustramines A and C, (±)-Flustramide A, and (−)- and (+)-Debromoflustramines A","Here we describe the efficient total synthesis of the three title hexahydropyrrolo[2,3-b]indole alkaloids and debromo derivative from readily available indolin-3-ones using key domino reactions, olefination-isomerization-Claisen rearrangement (OIC), and reductive cyclization (RC). (+/-)-Flustramine C (5) was synthesized in five steps from 6-bromoindolin-3-one 9 via a key intermediate 13a. (+/-)-Flustramine A (1) has been obtained by reduction of flustramide A (6), which has been prepared in five steps from 13a. (+/-)-Debromoflustramine A (19) was provided in a similar manner from 13b. The (-)- and (+)-enantiomers of 19 were synthesized through optical resolution of (+/-)-carboxylic acid 17b using (R)-4-phenyloxazolidin-2-one.",10.1021/jo800984a,2008-06-25,0.6543684651052284
Angewandte Chemie International Edition,Synthesis and Biological Activity of Largazole and Derivatives,A modular synthesis of the marine natural product largazole and related synthetic analogues is described. Largazole was prepared in 19 % overall yield through a synthetic route with a longest linear sequence of nine steps. Activity tests showed the necessity of the thiobutenyl moiety for antiproliferative activity.,10.1002/anie.200802043,2008-07-16,0.6543604731833879
Journal of the American Chemical Society,Gram-Scale Enantioselective Synthesis of (+)-Lucidumone,"The first enantioselective total synthesis of (+)-lucidumone is described through a 13-step synthetic pathway (longest linear sequence). The key steps involve the formation of a bridged bicyclic lactone by an enantioselective inverse-electron-demand Diels-Alder cycloaddition, C-O bond formation to assemble two fragments, and a one-pot retro-[4 + 2]/[4 + 2] cycloaddition cascade. The synthesis is scalable, and more than one gram of natural product was synthesized in one batch.",10.1021/jacs.2c08760,2022-09-23,0.6543575238877916
Journal of Organic Chemistry,A Chemoenzymatic Dynamic Kinetic Resolution Approach to Enantiomerically Pure (<i>R</i>)- and (<i>S</i>)-Duloxetine,"The synthesis of (R)-duloxetine is described. Dynamic kinetic resolution of β-hydroxynitrile rac-1 using Candida antarctica lipase B (CALB, N435) and ruthenium catalyst 6 afforded β-cyano acetate (R)-2 in high yield and in excellent enantioselectivity (98% ee). The subsequent synthetic steps were straightforward and (R)-duloxetine was isolated in 37% overall yield over 6 steps. The synthetic route also constitute a formal total synthesis of (S)-duloxetine.",10.1021/jo2003665,2011-03-31,0.6543492475668065
Tetrahedron,"An efficient synthetic route to 2-(1,2-dithiolan-3-yl)acetic acid. Trisnorlipoic acid and amide derivatives",,10.1016/s0040-4039(97)01319-1,1997-08-01,0.6543323847420288
Journal of Organic Chemistry,Asymmetric Total Synthesis of (+)-Apovincamine and a Formal Synthesis of (+)-Vincamine. Demonstration of a Practical “Asymmetric Linkage” between Aromatic Carboxylic Acids and Chiral Acyclic Substrates,"Asymmetric syntheses of (+)-apovincamine ( 1a ) and (+)-vincamine ( 2 ) are described. Construction of the pentacyclic diene lactam 14, a pivotal intermediate for synthesis of the cis-fused vincane-type alkaloids, began by Birch reduction−alkylation of the chiral benzamide 3 to give the 6-ethyl-1-methoxy-4-methyl-1,4-cyclohexadiene 4 . Conversion of 4 to 2,5-cyclohexadienone 5 (92% overall yield from 3 ) and HPLC analysis of 5 demonstrated the diastereomeric purity resulting from the Birch reduction−alkylation to be >100:1. Dienone 5 was converted to butyrolactone 9 (47% overall yield from 3 ), and 9 was coupled with tryptamine ( 10 ) to give the amide 11a . Amido keto aldehyde 13 was obtained from 11a, and acid-catalyzed tricyclization and subsequent base-induced elimination of MeOH provided the desired cis-fused pentacyclic diene lactam 14 . Examination of the two-step process 13 → 14 revealed a novel base-induced epimerization at C(21) which served to interconvert 14 and 17, possibly by the involvement of a homoenolate. Diene lactam 14 was converted to (+)-apovincaminal 20a, an intermediate in the synthesis of (+)-apovincamine ( 1a ) reported by Winterfeldt and co-workers. A new procedure for conversion of 20a to 1a involves conversion of 20a to the acetal 20b and treatment of 20b with NBS/AIBN in CCl 4 . The conversion of 1a to vincamine ( 2 ) has been reported by Oppolzer and co-workers.",10.1021/jo961603p,1997-03-01,0.6543313607237486
Organic Process Research & Development,Development of a Scalable Synthesis of a Common Eastern Tricyclic Lactone for Construction of the Nodulisporic Acids,"A scalable, second-generation synthesis of the densely functionalized eastern tricyclic lactone (+)- 6, a common intermediate, for construction of the nodulisporic acids has been achieved. Modifications to the first-generation route now permit access to (+)- 6 in 17 steps with an overall 16.5% yield. Key carbon−carbon bond constructions include a Kirk−Petrow (phenylthio)methylation, a Sc(OTf) 3 -catalyzed hydroxymethylation, a Stille carbonylation, and a Koga three-component, conjugate addition−alkylation sequence.",10.1021/op060204l,2006-12-23,0.654329249138827
Journal of Organic Chemistry,Total Synthesis of the Repeating Unit of <i>Streptococcus pneumoniae</i> Zwitterionic Polysaccharide Sp1,"Reported herein is the total synthesis of the trisaccharide repeating unit of Streptococcus pneumoniae zwitterionic polysaccharide Sp1 containing a rare sugar, 2-acetamido-4-amino-2,4,6-trideoxy- d -galactose (AAT), and three consecutive 1,2- cis -glycosidic linkages. The total synthesis was completed via highly stereoselective glycosylations and late-stage oxidation as key steps involving a longest linear sequence of 21 steps with 4.4% overall yield.",10.1021/acs.joc.1c02409,2021-12-03,0.6543256064021858
Synthesis,Synthesis of (2-{4-[4-Fluoro-3-(trifluoromethyl)phenyl]-2-piperidin-4-yl-1H-imidazol-1-yl}ethyl)dimethylamine,"An efficient eight-step synthesis of the title compound, starting from oxoacetic acid monohydrate, was developed. Condensation of oxoacetic acid monohydrate with N , N -dimethylethanamine followed by reductive amination and protection gave N -( tert -butoxycarbonyl)- N -[2-(dimethylamino)ethyl]glycine. Activation of this intermediate with 1,1′-carbonylbis-1 H -imidazole followed by treatment with (methoxyamino)methane gave tert -butyl [2-(dimethylamino)ethyl]{2-[methoxy(methyl)amino]-2-oxoethyl}carba­mate, which upon reaction with [4-fluoro-3-(trifluoromethyl)phenyl]magnesium bromide, generated in situ, and subsequent deprotection gave 2-{[2-(dimethylamino)ethyl]amino}-1-[4-fluoro-3-(trifluoromethyl)phenyl]ethanone dihydrochloride. Coupling of this diamine with an activated carboxylic acid gave tert -butyl 4-{1-[2-(dimethylamino)ethyl]-4-[4-fluoro-3-(trifluoromethyl)phenyl]-1 H -imidazol-2-yl}piperidine-1-carboxylate, which on treatment with sodium acetate in ethanol followed by deprotection in situ and neutralization gave the title compound in good yield.",10.1055/s-0033-1338467,2013-04-16,0.6543224920100769
Synthesis,"A Convenient Synthesis of Pyrrolo[3,4-<i>c</i>]quinolines","A new route to the pyrrolo[3,4-c]quinoline ring system has been developed. The synthesis proceeds stereoselectively in three steps, using 1,3-dipolar cycloaddition of azomethine ylides as a key step. First, a series of 4-arylpyrrolidine-3-carboxylic acids have been prepared from the appropriate cinnamic esters and a nonstabilized azomethine ylide. The reduction of a nitro group on the aromatic ring was followed by acid-catalyzed intramolecular lactam formation.",10.1055/s-2003-42425,2003-01-01,0.6542821129992146
Organic Letters,"Diastereoselective, Multicomponent Synthesis of Pyrrolopyrazinoquinazolinones via a Tandem Quinazolinone Rearrangement/Intramolecular Ring Closure of Tautomeric (<i>Z</i>)-Benzamidines","An expedient route to enantiopure, diastereomeric pyrrolopyrazinoquinazolinones was developed following the discovery of a domino quinazolinone rearrangement–intramolecular cyclization of N–H benzamidines. A Ugi–Mumm–Staudinger sequence employing an optically pure proline derivative gave quinazolinones that, upon N -Boc deprotection, rearranged to tautomeric Z -benzamidines. Subsequent spontaneous cyclization afforded 15 diastereomeric pyrazinoquinazolinone pairs in up to 83% overall yield and 89:11 d.r which were separated easily via routine chromatographic purification—the only one required in the entire process.",10.1021/acs.orglett.1c01955,2021-07-12,0.6542789933999487
Journal of Organic Chemistry,"Stereoselective Preparation of Ceramide and Its Skeleton Backbone Modified Analogues via Cyclic Thionocarbonate Intermediates Derived by Catalytic Asymmetric Dihydroxylation of α,β-Unsaturated Ester Precursors","A novel and efficient synthetic route to ceramide 1a and skeleton backbone modified ceramide analogues 1b,c is reported. The syntheses utilize osmium-catalyzed asymmetric dihydroxylation of (E)-alpha, beta-unsaturated ester 5a-c as the chiral induction step, with the desired configurations in the products 1a-c, 2a, and 13 being generated by regioselective azide substitution at the alpha position of alpha,beta-dihydroxyesters 6a-c via a cyclic thionocarbonate intermediate. Azido esters 10a-c are converted to the corresponding ceramides 1a-c by a sequence of azide reduction, N-acylation, ester reduction (NaBH(4)/LiBr), and Birch reduction of the triple bond (Li, EtNH(2)). These seven- to eight-step syntheses afford the target compounds 1a-c with excellent stereocontrol and in 30-42% overall yields. Furthermore, propargylic alpha-azido-beta-hydroxyester 10a is converted to D-erythro-sphingosine 2a via simultaneous reduction of the triple bond, azido, and ester functional groups with LiAlH(4), providing a highly concise and practical four-step synthesis of this key naturally occurring sphingolipid. The L-erythro stereoisomers are also available in high enantiomeric purity by the method described herein.",10.1021/jo001226n,2000-10-06,0.6542652145095301
Organic Letters,Synthesis of Fully Substituted Polyhydroxylated Pyrrolizidines via Cope–House Cyclization,Total synthesis of the proposed structure of (-)-hyacinthacine C(5) and its epimers at C6 and C7 is described. A key step of the synthesis was the construction of the bicyclic pyrrolizidine system by means of a nucleophilic addition of a dithiane to a cyclic nitrone followed by a Cope-House cyclization.,10.1021/ol201749c,2011-07-28,0.6542627387239638
Angewandte Chemie International Edition,Total Synthesis of a Protected Aglycon of the Kedarcidin Chromophore,"Strong support for the recently proposed structure of the kedarcidin chromophore has been obtained through the convergent synthesis of the aglycon. The key features of the synthesis are an efficient assembly of the four fragments, a novel strategy involving an alkynyl epoxide, a cerium amide promoted nine-membered diyne ring cyclization, and a SmI2-mediated reductive 1,2-elimination. TBS=tert-butyldimethylsilyl, MOM=methoxymethyl.",10.1002/anie.200805518,2008-12-31,0.654252719996877
Journal of the American Chemical Society,Total Synthesis of Baccatin III and Taxol,An intramolecular Heck reaction ( 90 → 91 ) serves as the key step in the total synthesis of the titled compounds. The synthetic route is based on utilizing the Wieland−Miescher ketone ( 5 ) as a matrix to provide the C and D rings of the targets and to provide functionality implements for joining this sector to an A ring precursor ( 6 ). Catalytically induced enantiotopic control and early emplacement of the oxetane are other features of the route.,10.1021/ja952692a,1996-01-01,0.6542357601105276
Organic Process Research & Development,"A Simple and Commercially Viable Process for Improved Yields of Metopimazine, a Dopamine D<sub>2</sub>-Receptor Antagonist","An efficient, practical, and commercially viable manufacturing process was developed with ≥99.7% purity and 31% overall yield (including four chemical reactions and one recrystallization) for an active pharmaceutical ingredient, called Metopimazine ( 1 ), an antiemetic drug used to prevent emesis during chemotherapy. The development of two in situ, one-pot methods in the present synthetic route helped to improve the overall yield of 1 (31%) compared with earlier reports (<15%). For the first time, characterization data of API ( 1 ), intermediates, and also possible impurities are presented. The key process issues and challenges were addressed effectively and achieved successfully.",10.1021/acs.oprd.7b00052,2017-04-27,0.6542310430499005
Tetrahedron,"A stereoselective synthesis of cyclohexylnorstatine, the key component of a renin inhibitor",,10.1016/s0040-4039(00)97574-9,1990-01-01,0.6542148451413934
Organic Letters,A Novel Approach toward the Synthesis of Kendomycin:  Selective Synthesis of a <i>C</i>-Aryl Glycoside as a Single Atropisomer,"[reaction: see text] A convergent and concise route to an advanced precursor 2b of kendomycin (1) has been developed by applying a S(N)1 ring cyclization as a key step. The resulting C-aryl glycoside was initially isolated as a rotameric mixture, but after MOM protection of the o-hydroxyl of the phenol, the conformation was frozen to the desired kendomycin-like atropisomer.",10.1021/ol035846x,2003-11-01,0.654183548058636
Angewandte Chemie International Edition,"Total Synthesis of (+)‐Scyphostatin, a Potent and Specific Inhibitor of Neutral Sphingomyelinase","The five crucial steps in the first total synthesis of (+)-scyphostatin from D-arabinose involve (see picture): a) stereoselective aldol coupling to form a quaternary stereocenter, b) ring-closing metathesis (RCM) to construct the cyclohexene ring, c) Negishi coupling for the preparation of the fatty acid side chain, d) amide formation to connect the cyclohexene and fatty acid segments, e) stereospecific epoxide-ring formation.",10.1002/anie.200454192,2004-08-09,0.6541827436834268
Synlett,"Efficient Synthesis of 2-Unsubstituted1,3-Selenazoles","Two new and efficient methods for the synthesis of 2-unsubstituted 1,3-selenazoles, the fragmentation of 2-benzoyl-1,3-selenazoles and the cyclization of α-bromoketones with seleno­formamide, are reported.",10.1055/s-2003-39884,2003-01-01,0.6541239611246766
Journal of Organic Chemistry,Synthesis of Rings DEF of Solanoeclepin A,"An improved synthesis of rings DEF of solanoeclepin A has been achieved from ent -Hajos Parrish ketone. A key tricyclo[5.3.2.0 1,6 ]decene intermediate having an additional vinyl group as a precursor of a hydroxyl functionality was synthesized, in which the key steps included (i) a [2,3]-Wittig rearrangement to provide trans -hydroindene with C11( R )-configuration, (ii) the introduction of a vinyl group as a masked OH at C6, (iii) an oxymercurative aldol to synthesize the tricyclo[5.3.2.0 1,6 ]decene moiety, (iv) an oxidative C–C bond cleavage to yield an aldehyde and an unsaturated methyl ketone, and (v) a radical cyclization for the cyclobutane ring formation to provide the tricyclo[5.2.1.0 1,6 ]decene compound.",10.1021/acs.joc.6b02886,2017-01-24,0.6541222931888333
Organic Process Research & Development,Development of a Phase Transfer Catalyzed Asymmetric Synthesis for an Estrogen Receptor Beta Selective Agonist,"A practical asymmetric synthesis of the estrogen receptor beta selective agonist (7β-9aβ)-1,4-dichloro-2-hydroxygibba-1(10a),2,4,4b-tetraen-6-one ( 1 ), proceeding by way of six isolated intermediates and without recourse to chromatography, is described. Highlights of the process route developed are two chemoselective chlorinations, a lithiated hydrazone alkylation and an asymmetric Michael addition of indanone 11 to methyl vinyl ketone (using 15 mol % of cinchonine-derived catalyst 20g ) to set the all-carbon quaternary asymmetric stereocenter. The challenges addressed in scaling the latter heterogeneous biphasic phase transfer reaction to 44 mol (14 kg) scale are discussed in detail. Overall, the chemistry developed has been used to prepare >6 kg of drug candidate 1 in 18% overall yield and with >99% ee.",10.1021/op700178q,2007-11-10,0.6541134633944627
Synlett,A Facile and Convenient Synthesis of (±)-Biotin via MgCl2/Et3N-Mediated C–C Coupling and Mitsunobu Reaction,"A synthesis of (±)-biotin is described starting from simple starting materials viz. cyclohexanone and amino malonic acid ester. The key steps involved are MgCl 2 /Et 3 N coupling of amino malonic acid ester derivative and acid chloride, Mitsunobu reaction, ozonolysis, Staudinger reduction, novel urea formation, and subsequent dibenzylation. This approach is economical and involves high-yielding steps and simple reaction conditions.",10.1055/s-0034-1379365,2014-11-05,0.6541075968399078
Synthesis,A Modular Synthesis of 2-Alkyl- and 2-Arylchromans via a Three-Step Sequence,"A convergent three-step method for the synthesis of 2-substituted chromans is described. These results have been accomplished via the Heck coupling of readily accessible allylic alcohols and 2-iodophenols, followed by reduction and Mitsunobu cyclization. The utility and generality of this method is demonstrated through the synthesis of a series of 2-aryl-, 2-heteroaryl- and 2-alkylchromans, as well as an azachroman derivative. The asymmetric version of this approach via a Noyori-catalyzed ketone reduction and subsequent cyclization is likewise highlighted.",10.1055/s-0036-1588075,2016-10-14,0.654106258068422
Organic Process Research & Development,A Practical Synthesis of Multitargeted Antifolate LY231514,"A concise and scalable synthesis of LY231514 ( 1 ), a new pyrrolo[2,3- d ]pyrimidine-based antitumor agent, is presented. Reaction of 2-bromo-4-arylbutanal 9 with 2,4-diamino-6-hydroxypyrimidine ( 10 ) regioselectively provided pyrrolo[2,3- d ]pyrimidine 11, representing the core structure of the drug, in good yield. Assimilation of the glutamic acid residue by conventional means completed the synthesis. Development of the optimized synthetic route emphasized avoiding isolation of the relatively unstable aldehyde and bromoaldehyde intermediates.",10.1021/op9802172,1999-04-30,0.6541050524837213
Angewandte Chemie International Edition,"Macrocyclization by Nickel‐Catalyzed, Ester‐Promoted, Epoxide–Alkyne Reductive Coupling: Total Synthesis of (−)‐Gloeosporone",Ringing the changes: The total synthesis of the title compound centers around a novel strategy that employs a nickel(0)-phosphine complex and triethyl borane in an efficient closure of a 14-membered ring through C--C bond formation (see scheme; cod=cyclooctadiene). The synthesis was accomplished in 10 steps and in approximately 9 % overall yield.,10.1002/anie.200902079,2009-06-17,0.6540822542559862
Journal of Organic Chemistry,Efficient Fluorination with Tetrabutylammonium Dihydrogen Trifluoride in a Novel Approach toward 1-α-Fluoro-25-hydroxy-vitamin D<sub>3</sub> Analogues,"The known, but hardly accessible, A-ring phosphine oxide 20, a building block for 1-alpha-fluoro-25-hydroxy-vitamin D(3), was prepared by a new route in gram amounts from (S)-(+)-carvone in 20 steps and 0.6% overall yield. Fluorine was introduced at an early stage by the completely regio- and stereoselective trans-diaxial opening of key-epoxide 5 with neat tetrabutylammonium dihydrogen trifluoride at 95 degrees C. The required 2-carbon chain extension of cyclohexanol 13 was accomplished in moderate yield via S(N)' substitution with cesium phenylselanyl acetate followed by Ireland-Claisen rearrangement of the resulting ester 15. Spontaneous elimination of the derived phenyl selenoxide led stereorandomly to a 1:1 mixture of dienoates E/Z-17, which was transformed into 20 as previously described.",10.1021/jo980764l,1998-09-11,0.6540718951391424
Organic Process Research & Development,Improved Synthetic Route to Dexamethasone Acetate from Tigogenin,"In the synthesis of dexamethasone acetate from tigogenin, the introduction of the 17α-hydroxy-16α-methyl and the 1,4-diene moieties was improved. For the introduction of the 17α-hydroxy-16α-methyl moiety, the key step, epoxidation, was accomplished in high yield with peracetic acid in a buffer solution of sodium acetate and acetic acid (overall yield from 17-ene substrate to 17α-hydroxy-16α-methyl intermediate: 95.3%). Then the introduction of the 1,4-diene in the A-ring was greatly improved by bromination−dehydrobromination, in which dehydrobromination proceeded smoothly in a solvent system that was a mixture of DMF and 6% of water (82.6% isolated yield of 1,4-diene based on 3-oxo compound).",10.1021/op9700338,1997-11-01,0.6540570403570288
Organic Process Research & Development,Preclinical Toxicology Supply for a Complex API Enabled by Asymmetric Catalysis and Rapid Chemical Development: IL-17A Inhibitor LY3509754,"The chemical development and production of sufficient amounts of IL-17A inhibitor LY3509754 to enable preclinical toxicology studies is described. LY3509754 is a complex small molecule that features three stereocenters, which comprised much of the synthetic challenge. Stereoselective hydrogenation and biocatalysis enabled access to all stereocenters. The most significant challenge was installation of the chiral methoxymethyl side chain, specifically, formation of the sp2–sp3 C–C bond from reasonable raw materials and establishment of the benzylic amine stereocenter. Given prior experience with structural analogs, we were able to use a hybrid approach to the synthesis, with key building blocks being available on large-scale from the previous efforts. Historical knowledge combined with rapid route scouting and development allowed us to invent a scalable route to LY3509754 in about seven months and deliver 430 g to accelerate the preclinical toxicology studies.",10.1021/acs.oprd.4c00539,2025-03-06,0.6540531132260353
Synthesis,A Convenient New Synthesis of A Naproxen Precursor,"A precursor of Naproxen, 2-(6-methoxy-2-naphthyl)propenoic acid was synthesized in good yield from commercially available 6-methoxy-2-naphthaldehyde in three steps. The synthesis includes an unprecedented one-step reduction of acrylic acid ethyl ester to propenoic acid ethyl ester in high yield.",10.1055/s-2002-33920,2002-09-09,0.6540479668159047
Organic Process Research & Development,Development and Scale-Up of a Key Copper-Catalyzed Biaryl Ether Formation for the Multikilogram Synthesis of Emprumapimod,"Emprumapimod was a p38α MAPK inhibitor developed for LMNA-related dilated cardiomyopathy. One key modification from the discovery synthesis to the manufacturing synthesis involved moving the biaryl ether formation toward the end of the synthetic sequence. Herein, we discuss the redesigned route to suit large-scale manufacture. The development of a copper-catalyzed biaryl etherification reaction is detailed, including high-throughput experiments, process development and optimization, and purification. Subsequent amide formation afforded desired emprumapimod, delivering 82 kg of API across three batches. We anticipate this report will further support the utilization of nonprecious metal catalysis in pharmaceutical manufacture processes.",10.1021/acs.oprd.4c00052,2024-03-26,0.6540410332390099
Journal of the American Chemical Society,Total Synthesis of (+)-Tedanolide,"A convergent, stereocontrolled total synthesis of (+)-tedanolide (1), an architecturally complex marine antitumor macrolide, has been achieved in 31 steps (longest linear sequence). Highlights of the synthesis comprise a highly efficient dithiane union, followed by an Evans-Tishchenko ""oxidation"" to enable formation of the seco-ester in the presence of an oxidatively labile dithiane, a highly refined protecting group strategy, and a chemo- and stereoselective epoxidation at C(18,19).",10.1021/ja073329u,2007-08-11,0.6540231196582511
Synlett,A Stereocontrolled Synthesis of a Key Intermediate to (+)-Thienamycin,"All articles of this category A formal synthesis of (+)-thienamycin was achieved by the enantioselective preparation of key intermediate azetidinone 2 [benzyl (2 R ,3 S )-3-{( S )-1-hydroxyethyl}-4-oxo-2-azetidineacetate] via an intramolecular nitrone 1,3-dipolar cycloaddition.",10.1055/s-1991-20786,1991-01-01,0.6540034284997004
Organic Letters,A Pyridine Dearomatization Approach for the Gram Scale Synthesis of (±)-Sparteine,"Both enantiomers of sparteine have suffered from pricing and supply chain variability, which has inspired efforts toward efficient chemical synthesis. Here, we build upon our reported synthesis of the matrine-type lupin alkaloids in order to synthesize (±)-sparteine. Specifically, selective quenching of the cyclization between glutaryl chloride and pyridine with methanol provides a functionalized quinolizidine core that was elaborated to (±)-sparteine in six additional steps on gram scale. This synthesis provides a scalable route to sparteine from inexpensive commodity chemicals utilizing a dearomative cyclization. In addition, this route provides concise access to (±)-lupinine.",10.1021/acs.orglett.3c03242,2023-11-10,0.6539984258525461
Synlett,Chiron Approach for the Total Synthesis of Brevipolide M,Abstract An efficient stereoselective synthesis of brevipolide M was established in 13 linear steps and 17.8% overall yields based on chiron approach. The key steps of our synthesis involved tandem Wittig olefination–tetrahydrofuran cyclization and sequential ring-closing metathesis (RCM)–double-bond migration in one-pot processes.,10.1055/a-1730-9857,2022-01-04,0.6539962967616875
Synlett,Stereoselective Total Synthesis of Rhoiptelol B via Prins Cyclization,"The stereoselective total synthesis of rhoiptelol B, a diaryl­heptanoid isolated from Rhoiptelea chiliantha is described. The tetrahydropyran ring was constructed by using Prins cyclization. The key steps involved in this synthesis are Prins cyclization, Mistunobu inversion, cross metathesis, Sharpless asymmetric dihydroxylation, and hydrogenolysis.",10.1055/s-0033-1340181,2014-02-11,0.6539962371227891
Journal of Organic Chemistry,Development of a β-C–H Bromination Approach toward the Synthesis of Jerantinine E,"The development of an asymmetric and highly convergent three-component synthesis of the functionalized ABC ring system of the Aspidosperma alkaloid jerantinine E is reported. The presented synthetic strategy relies on our recently developed method for the one-pot β-C-H bromination of enones, which allows for rapid construction of the tricyclic tetrahydrocarbazolone core via a palladium-catalyzed amination and oxidative indole formation. Moreover, a secondary amine building block that contains all carbon atoms of the D and E ring of the natural product could be installed in three additional steps.",10.1021/acs.joc.7b01095,2017-06-16,0.65397303655483
Synthesis,Late-Stage Sulfoximination: Improved Synthesis of the Anticancer Drug Candidate Atuveciclib,"An efficient synthesis of racemic atuveciclib was accomplished in five steps with an excellent 51% overall yield, using cheap reagents and mild reaction conditions. The key sulfoximination reaction was realized during the last step of the synthesis from the corresponding sulfide.",10.1055/s-0037-1610316,2018-11-05,0.6539705559431647
Journal of Organic Chemistry,"<i>De Novo</i> Asymmetric Synthesis of Avocadyne, Avocadene, and Avocadane Stereoisomers","asymmetric synthesis of all possible stereoisomers of two polyketide natural products, avocadyne, avocadene, and the saturated variant avocadane, is described. The stereodivergent synthesis of the 12 congeners is accomplished in 4-6 steps from an achiral acylpyruvate derivative, which, in turn, is prepared in five steps from commercially available materials. The approach uses, sequentially, a Noyori asymmetric reduction, a diastereoselective chelate- or directed reduction of a β-hydroxyketone, and an ester reduction to a primary alcohol.",10.1021/acs.joc.9b02391,2019-10-24,0.6539661138546625
Synthesis,Facile Synthesis of <i>ortho</i>-Halo-Substituted 4-Aryl-2-Aminobutyric Acids,"Herein we describe an efficient and practical route for the regioselective synthesis of 4-(5-bromo/chloropyrazol-1-yl)-2-aminobutyric acids. The compounds have been prepared by regioselective C-5 halogenation of 1-(3,3-dimethoxypropyl)-1H-pyrazole followed by a Strecker synthesis. In addition, Boc-protected 2-amino-4-(2-chlorophenyl)butyric acid and 2-amino-4-(3-chloropyridin-2-yl)butyric acid have been synthesized.",10.1055/s-2008-1032194,2008-03-01,0.6539630112702806
Journal of Organic Chemistry,Convergent and Scalable Second-Generation Synthesis of the Fully Functionalized HIJKLMN-Ring Segment of Caribbean Ciguatoxin C-CTX-1,"A highly convergent and scalable second-generation synthesis of the fully functionalized HIJKLMN-ring segment of Caribbean ciguatoxin C-CTX-1, the primary toxin responsible for ciguatera fish poisoning in the Caribbean Sea and the Northeast Atlantic regions, has been accomplished. Key aspects of the synthetic approach include the efficient syntheses of the HI- and KLM-ring fragments on gram scales, a convergent fragment coupling toward the HIJKLM-ring skeleton based on the Suzuki-Miyaura coupling strategy, and optimized iron hydride-catalyzed hydrogen atom transfer-mediated olefin coupling conditions for constructing the N-ring.",10.1021/acs.joc.4c02723,2024-12-04,0.6539504699446445
Synlett,Stereoselective Synthesis of the Key Intermediates of the HIV Protease Inhibitor Fosamprenavir and Its Diastereomer,"Highly stereoselective Henry reaction has been used in the synthesis of the fosamprenavir precursor (2 S ,3 R )- N - tert- butyl­oxycarbonyl-2-amino-3-hydroxy-1-phenyl-4-nitrobutane and its 2 S ,3 S diasteromer from N-tert- butyloxycarbonyl-( S )-phenylalaninal and nitromethane. The complex of (2 S ,5 R )- or (2 R ,5 S )-5-isopropyl-5-methyl-2-(pyridine-2-yl)imidazolidine-4-one with copper(II) acetate has been used as the catalyst which provided the product with 2 S ,3 R absolute configuration (dr = 90:10, overall yield 89%) or 2 S ,3 S (dr = 99:1, overall yield 94%), respectively.",10.1055/s-0033-1338803,2013-05-08,0.6539476770107611
Tetrahedron,Chiral base route to cyclic polyols: asymmetric synthesis of aminodeoxyconduritols and conduritol F,,10.1016/s0040-4039(01)01706-3,2001-11-01,0.6539231517357124
Journal of the American Chemical Society,Total Synthesis of (−)-Anominine,"The first total synthesis of anominine has been achieved, and the absolute configuration of the product has been determined. The key features include the development of a new, highly efficient organocatalyzed method for the asymmetric synthesis of Wieland-Miescher ketone building blocks, an unusual selenoxide [2,3]-sigmatropic rearrangement, and a ZrCl(4)-catalyzed indole coupling as well as several chemoselective transformations controlled by the structurally congested nature of the bicyclic core.",10.1021/ja101994q,2010-04-12,0.653893946205024
Organic Letters,Total Synthesis of the Opioid Agonistic Indole Alkaloid Mitragynine and the First Total Syntheses of 9-Methoxygeissoschizol and 9-Methoxy-<i>N</i><sub>b</sub>-methylgeissoschizol,"An enantiospecific method for the synthesis of 4-methoxytryptophan has been developed via a regiospecific Larock heteroannulation and employed for the first total syntheses of 9-methoxygeissoschizol and 9-methoxy-Nb-methylgeissoschizol, as well as the total synthesis of the opioid agonistic alkaloid mitragynine. The asymmetric Pictet-Spengler reaction and a Ni(COD)2-mediated cyclization served as key steps.",10.1021/ol071220l,2007-08-01,0.6538914399359398
Organic Process Research & Development,Crystallization-Based Synthetic Route to Antimalarial Agent BRD5018: Diazocene Ring Formation via a Staudinger-aza-Wittig Reaction on an Azetidine-Ribose Template,"The development of an entirely crystallization-based synthetic route to the antimalarial BRD5018 is described, which assembles a structurally complex bicyclic azetidine scaffold adorned with five stereogenic centers without the need for any chromatographic separations. A diastereoselective glycine ester Claisen rearrangement, diastereomeric salt resolution, and diastereoselective iodo-lactonization are utilized to provide an efficient access to three contiguous stereogenic centers on an acyclic template with the desired relative and absolute configurations. A tandem aziridine ring-opening/azetidine ring-closure on the derived 2-amino-1,4-diol template was developed to efficiently establish the all- cis trisubstituted azetidine scaffold with the proper ancillary functionality for end-game maneuvers. d -Ribose-2,3-acetonide provided a conveniently differentiated vicinal syn -diol suitable for the planned reductive amination/periodate cleavage/Staudinger-aza-Wittig sequence to form the eight-membered diazocene ring. An early quantitative installation of the diaryl acetylene moiety via a Sonogashira coupling on an electronically matched methyl 4-bromocinnamate circumvented a low-yielding, late-stage reaction in the first-generation synthesis. Multiple crystalline intermediates enabled the complete removal of chromatography from the synthesis resulting in a substantially reduced cost and waste generation with enhanced throughput and quality control.",10.1021/acs.oprd.1c00225,2021-09-15,0.653888803589098
Organic Process Research & Development,A Scalable Process for the Synthesis of the Bcl Inhibitor Obatoclax,"Recently we created the novel indolylprodigiosin derivative 2 (obatoclax) and demonstrated its ability to antagonize multiple members of the B-cell lymphoma (Bcl) family of antiapoptotic proteins. The compound has shown potent anticancer activity in several animal tumor models. Obatoclax is now in Phase 1b and 2 clinical trials directed against multiple hematologic and solid tumor malignancies. To support its clinical development, a new scalable synthesis was required. Obatoclax has been prepared using a three-step synthesis, starting from commercially available 4-methoxy-3-pyrrolin-2-one. The reaction sequence involves a haloformylation reaction followed by a Suzuki cross-coupling reaction with an indole-2-boronic acid. The synthesis is completed by an acid-mediated condensation with 2,4-dimethyl-1 H -pyrrole.",10.1021/op7001613,2007-11-01,0.6538845088144977
Angewandte Chemie International Edition,Modular Access to Diverse Chemiluminescent Dioxetane‐Luminophores through Convergent Synthesis,"Adamantyl-dioxetane luminophores are an important class of chemiluminescent molecular probes for diagnostics and imaging. We have developed a new efficient synthetic route for preparation of adamantyl-enolether as precursors for dioxetane chemiluminescent luminophores. The synthesis is convergent, using an unusual Stille cross-coupling reaction employing a stannane-enolether, to directly afford adamantyl-enolether. In a following simple step, the dioxetane is obtained by oxidation of the enolether precursor with singlet-oxygen. The scope of this synthetic route is broad since a large number of haloaryl substrates are either commercially available or easily accessible. Such a late-stage derivatization strategy simplifies the rapid exploration of novel luminogenic molecular structures in a library format and simplifies the synthesis of known dioxetane luminophores. We expect that this new synthetic strategy will be particularly useful in the design and synthesis of yet unexplored dioxetane chemiluminescent luminophores.",10.1002/anie.202202187,2022-03-08,0.6538790733478338
Angewandte Chemie International Edition,"Synthesis of Rimocidinolide Methyl Ester, the Aglycone of (+)‐Rimocidin","An efficient, convergent route based on cyanohydrin acetonide couplings was used for the synthesis of the aglycone of rimocidin, rimocidinolide methyl ester (1). Cyanohydrin acetonides were used as β-hydroxyketone synthetic equivalents in the assembly of the polyol chain.",10.1002/anie.200453697,2004-05-12,0.6538790597610998
Journal of the American Chemical Society,Sequential C–H Arylation and Enantioselective Hydrogenation Enables Ideal Asymmetric Entry to the Indenopiperidine Core of an 11β-HSD-1 Inhibitor,"A concise asymmetric synthesis of an 11β-HSD-1 inhibitor has been achieved using inexpensive starting materials with excellent step-economy at low catalyst loadings. The catalytic enantioselective total synthesis of 1 was accomplished in 7 steps and 38% overall yield aided by the development of an innovative, sequential strategy involving Pd-catalyzed pyridinium C–H arylation and Ir-catalyzed asymmetric hydrogenation of the resulting fused tricyclic indenopyridinium salt highlighted by the use of a unique P,N-ligand (MeO-BoQPhos) with 1000 ppm of [Ir(COD)Cl] 2 .",10.1021/jacs.6b09764,2016-10-30,0.6538498342804366
Journal of Organic Chemistry,Studies toward the Total Synthesis of the Oxindole Alkaloid Gelsedine:  An Efficient Allene-Terminated <i>N</i>-Acyliminium Ion Cyclization,"This paper reports the synthesis of the advanced intermediate 26 in a projected synthesis of enantiopure ent -gelsedine ( 5 ). The route starts from ( S )-malic acid and features the creation of four new stereocenters with complete control of stereochemistry. The key step is a novel allene-terminated N -acyliminium ion cyclization that leads to the required 7-azabicyclo[4.2.1]nonane-4,8-dione skeleton. Additional functionalities including the C-8 ethyl and the C-9 hydroxymethyl are introduced in an efficient manner.",10.1021/jo971510n,1997-12-01,0.6538193715032984
Synthesis,Flexible and Simple Route for the Stereoselective Synthesis of Trisubstituted γ-Butyrolactones: Total Synthesis of (+)-Blastomycinone and its Analogs,"A flexible route for the stereoselective synthesis of trisubstituted γ-butyrolactones, namely (+)-blastomycinone and its analogs, is devised by the Sharpless asymmetric epoxidation and the regioselective ring opening reaction with dibutylcopper lithium as the key steps to introduce the requisite alkyl chain.",10.1055/s-2004-829173,2004-01-01,0.6538079867156571
Organic Letters,Target-Directed Synthesis of Antibacterial Drug Candidate GSK966587,"An efficient enantioselective total synthesis of the potent antibiotic GSK966587 was accomplished. Highlights of the synthesis include two innovative Heck reactions, a highly selective zincate base directed ortho-metalation, Sharpless asymmetric epoxidation, and a fully convergent final step fragment coupling.",10.1021/ol101235f,2010-07-15,0.653805431841881
Synthesis,Efficient Synthesis of N-[4-(4-Chlorophenyl)butyl]-S-(3-piperidinopropyl)isothiourea (OUP-186) and Its Analogues Using 2-Nitrophenylacetyl Isothiocyanate: Application to Novel Histamine H3R Antagonists,"A potent histamine H 3 receptor antagonist OUP-186 with an S -alkyl- N -alkylisothiourea structure was synthesized using 3-phenylpropanoyl isothiocyanate (PPI) as an SCN source. The synthetic route was significantly improved by replacing 3-phenylpropanoyl isothiocyanate with 2-nitrophenylacetyl isothiocyanate (NPAI), giving a 74% overall yield in three steps from 4-(4-chlorophenyl)butylamine. In addition, the 2-nitrophenylacetyl isothiocyanate method successfully yielded two fluorine-containing analogues, and a shorter, C 2 homologue of OUP-186.",10.1055/s-0034-1380345,2015-03-19,0.6537735587151787
Tetrahedron,"Synthesis of the C-glycosidic analog of adenophostin A, a potent IP3 receptor agonist, using a temporary silicon-tethered radical coupling reaction as the key step",,10.1016/s0040-4039(00)00171-4,2000-04-01,0.6537583359531478
Organic Letters,"Toward the Synthesis of Thapsigargin:  Enantioselective Synthesis of 7,11-Dihydroxyguaianolides","[reaction: see text] The enantioselective synthesis of a 7,11-dihydroxyguaianolide bearing the stereochemistry present in thapsigargin, a potent and selective inhibitor of the Ca(2+) SERCA-ATPase pumps, is described. Starting from (+)-dihydrocarvone, the synthesis presents two key steps. The first one involves the photochemical rearrangement of a gamma,delta-unsaturated ketone eudesmane into the corresponding guaiane. The second step consists of the regioselective oxidation of an unprotected tetrahydroxylated ketone to provide a dihydroxylactone with the required stereochemistry.",10.1021/ol061024z,2006-06-01,0.6537553797488586
Organic Letters,Synthesis of the C9–C25 Subunit of Spirastrellolide B,"The synthesis of the C9-C25 subunit of the marine natural product spirastrellolide B is reported. The key synthetic features included the union of the two key fragments 5 and 6 via a Suzuki-Miyaura coupling reaction and a late-stage, one-pot sequential deprotection/cascade Achmatowicz rearrangement-spiroketalization to install the key spirocyclic intermediate present in the C9-C25 fragment of spirastrellolide B. The synthesis of the C9-C16 fragment 6 was accomplished via a phosphate tether mediated ring-closing metathesis (RCM), a subsequent hydroboration-oxidation protocol, followed by other stereoselective transformations in a facile manner. The spirocyclic intermediate was further functionalized utilizing a Lindlar/NaBH4 reduction protocol to furnish the C9-C25 subunit 3.",10.1021/acs.orglett.6b01248,2016-06-14,0.6537387781869508
Organic Letters,Construction of a Library of Rhodol Fluorophores for Developing New Fluorescent Probes,"A highly efficient and concise synthetic scheme for rhodol fluorophores is developed with palladium-catalyzed amination reaction as the key step. This new synthetic route is utilized to construct a rhodol library, potentially useful for the design of novel fluorescent probes.",10.1021/ol902706b,2010-01-12,0.653731014185759
Journal of Organic Chemistry,Total Synthesis of (+)-Lysergic Acid,"We report the enantioselective total synthesis of (+)-lysergic acid using two different strategies, which featured three metal-catalyzed reactions for the construction of the BCD three rings, involving Pd-catalyzed indole synthesis for the construction of the B ring, a ring-closing metathesis reaction for the formation of the D ring, and an intramolecular Heck reaction to forge the C ring. In synthetic strategy I, the synthesis was achieved in 20 steps following the ring construction sequence of BDC. In synthetic strategy II, the synthetic route was shortened to only 12 steps by following the ring construction sequence of DBC and using a 4-chlorotryptophan derivative for the intramolecular Heck reaction. Moreover, we also discussed an unsuccessful synthetic strategy.",10.1021/jo4018777,2013-10-10,0.6537227466706943
Organic Letters,"A Novel, Efficient, Diastereo- and Enantioselective Mukaiyama Aldol-Based Synthesis of a Vinyl Cyclopentanone Core Derivative of Viridenomycin","A strategy has been developed for a rapid seven-step construction of a chiral, nonracemic vinyl cyclopentanone building block as part of a synthetic approach to viridenomycin, using a diastereo- and enantioselective Mukaiyama aldol and intramolecular Knoevenagel condensation as key steps.",10.1021/ol7025262,2007-11-17,0.6537081314105186
Journal of Organic Chemistry,Total Synthesis of Ailanthoidol and Precursor XH14 by Stille Coupling,"Ailanthoidol 1, which can be isolated from Chinese herbal medicine, is achieved in which the longest linear sequence is only six steps in 48% overall yield from commercially available 5-bromo-2-hydroxy-3-methoxybenzaldehyde. The key transformations in the synthesis are the Stille coupling reactions of benzofuranyl bromide with stannanyl compounds. This synthetic strategy can be modified to give access to a variety of different ailanthoidol and XH14 analogues.",10.1021/jo020653t,2003-02-25,0.653708119741343
Angewandte Chemie International Edition,Total Synthesis of (−)‐Caprazamycin A,"Caprazamycin A has significant antibacterial activity against Mycobacterium tuberculosis (TB). The first total synthesis is herein reported and features a) the scalable preparation of the syn-β-hydroxy amino acid with a thiourea-catalyzed diastereoselective aldol reaction, b) construction of a diazepanone with an unstable fatty-acid side chain, and c) global deprotection with hydrogenation. This report provides a route for the synthesis of related liponucleoside antibiotics with fatty-acid side chains.",10.1002/anie.201411954,2015-01-22,0.6537045717283173
Journal of the American Chemical Society,Total Synthesis of (−)-Disorazole C<sub>1</sub>,The antimitotic natural product disorazole C1 was isolated in 1994 from the fermentation broth of the myxobacterium Sorangium cellulosum. We have developed a highly convergent and stereoselective total synthesis of this compound which establishes its relative and absolute configuration. Key features of our synthesis include a highly convergent strategy and selective functional group manipulations that minimize decomposition of the sensitive polyene macrodiolide.,10.1021/ja0443068,2004-11-04,0.653664672773342
Journal of Organic Chemistry,Studies toward the Synthesis of (+)-Palustrine:  The First Asymmetric Synthesis of (−)-Methyl Palustramate,"The stereoselective synthesis of (-)-methyl palustramate, a possible intermediate for the synthesis of (+)-palustrine, is described. The key step of the synthesis is a conformationally restricted Claisen rearrangement to afford the highly functionalized 1-benzylpipecolic ester 10. In addition, a new procedure for debenzylation of 1-benzylpiperidines (Li, (NH(2)CH(2))(2), Et(3)N, THF) was used to remove the benzyl protecting group where traditional methods failed.",10.1021/jo980749g,1998-10-01,0.6536397327415009
Journal of Organic Chemistry,A Convergent Total Synthesis of the Potent Cephalostatin/Ritterazine Hybrid -25-<i>epi</i> Ritterostatin G<sub>N</sub>1<sub>N</sub>,"The convergent synthesis of 25-epi ritterostatin GN1N is described for the first time, starting from hecogenin acetate (HA). Stereoselective dihydroxylation employing the chiral ligand (DHQ)2PHAL was used as the key step to introduce the C25 epi-stereocenter on the north 1 segment. The title compound was obtained through a coupling reaction between the C3-keto-azide (cstat North 1) and North G.",10.1021/jo401171q,2013-07-30,0.6536393309067666
Organic Process Research & Development,"Novel Stereoselective Syntheses of the Fused Benzazepine Dopamine D<sub>1</sub> Antagonist (6a<i>S</i>,13b<i>R</i>)-11-Chloro-6,6a,7,8,9,13b-hexahydro-7-methyl-5<i>H</i>- benzo[<i>d</i>]naphth[2,1-<i>b</i>]azepin-12-ol (Sch 39166):  1. Aziridinium Salt Based Syntheses","Several novel enantioselective syntheses of the dopamine D 1 antagonist (6a S,13b R )-11-chloro-6,6a,7,8,9,13b-hexahydro-7-methyl-5 H -benzo[ d ]naphth[2,1- b ]azepin-12-ol ( 2 ) are described in which the key intermediate was 1-(2,2-dimethoxyethyl)-1-methyl-1a,2,3,7b-tetrahydro-1 H -naphth[1,2- b ]aziridinium salt ( 20 ). The latter species was prepared either from 1-(2,2-dimethoxyethyl)-1a,2,3,7b-tetrahydro-1 H -naphth[1,2- b ]azirine ( 18 ) by methylation or from the tertiary amino alcohols 1-[(2,2-dimethoxyethyl)methylamino]-1,2,3,4-tetrahydro-2-naphthalenol ( 23 ) or 2-[(2,2-dimethoxyethyl)methylamino]-1,2,3,4-tetrahydro-1-naphthalenol ( 24 ) by tosylation and in situ ring closure. Regioselective trapping of 20 with Grignard reagent (4-chloro-3-methoxyphenyl)magnesium bromide ( 10 ) then afforded the trans amine 1-(4-chloro-3-methoxyphenyl)- N -(2,2-dimethoxyethyl)-1,2,3,4-tetrahydro- N -methyl-2-naphthalenamine ( 22 ), which was cyclized to give 11-chloro-6,6a,7,8,9,13b-hexahydro-7-methyl-12-methoxy-5 H -benzo[ d ]naphth[2,1- b ]azepine ( 9 ), a known precursor of 2 . Several enantioselective syntheses, including a Jacobsen epoxidation route, a de novo synthesis from l -homophenylalanine, and a classical salt resolution sequence, were developed for the preparation of the key intermediates in chiral form.",10.1021/op970121s,1998-04-26,0.6536296778385294
Journal of Organic Chemistry,"α,β-Unsaturated Diazoketones as Building Blocks to Piperidine Alkaloids: Total Synthesis of (−)-Cassine","High Resolution Image Download MS PowerPoint Slide The total synthesis of (−)-cassine, a piperidine alkaloid, was accomplished in 10 steps, starting from N -Cbz- O -TBDPS- l -serinal. Key transformations include the preparation of a novel α,β-unsaturated α′-methyl diazoketone, followed by its cyclization into a highly functionalized dihydropyridine-3-one via a cis -selective intramolecular N–H insertion reaction. This strategy was further extended to other α′-alkylated α,β-unsaturated diazoketones, enabling the synthesis of new dihydropyridine-3-ones with potential applications in the total synthesis of cassine derivatives.",10.1021/acs.joc.5c00729,2025-06-10,0.6536233428573631
Tetrahedron,An improved synthesis of the broad spectrum matrix metalloprotease inhibitor marimastat,,10.1016/s0040-4039(00)01376-9,2000-10-01,0.6536199916846176
Organic Letters,Enantioselective Total Synthesis of a Natural Iridoid,The first total synthesis of 6-hydroxy-7-(hydroxymethyl)-4-methylenehexahydrocyclopenta[c]pyran-1(3H)-one has been accomplished. A key feature of the synthesis includes facile construction of the bicyclic lactone intermediate via intramolecular Pd(0)-catalyzed allylic alkylation and the efficient transformation of this intermediate into the iridoid skeleton employing silicon tethered radical cyclization.,10.1021/ol201089f,2011-05-27,0.6535716645784052
Organic Process Research & Development,Optimization of a Kilogram-Scale Synthesis of a Potent Cycloartenol Triterpenoid-Derived γ-Secretase Modulator,This work describes the demonstration of a kilogram-scale synthesis of a γ-secretase modulator from a plant-sterol-derived starting material. Key to developing a synthetic route capable of delivering a kilogram of the target compound was the development of a four-reaction telescope process and a selective O-alkylation of a triol intermediate. These improvements enabled the successful delivery of kilogram-scale batches of API for preclinical development studies.,10.1021/op500072b,2014-04-30,0.6535644678547926
Organic Process Research & Development,A Concise Asymmetric Synthesis of A β-Lactam-Based Cholesterol Absorption Inhibitor,"A concise, four-step, asymmetric synthesis of a β-lactam-based cholesterol absorption inhibitor, Sch 57939, was developed. The discovery of a one-step enantio- and diastereoselective synthesis of a trans -β-lactam provided easy access to the desired three chiral centers. A novel zinc phenoxide-promoted ether synthesis was reported for the completion of the side chain.",10.1021/op990196r,2000-04-29,0.6535628430739119
Organic Letters,"Asymmetric Synthesis and Structure Revision of Guignardone H and I: Development of a Chiral 1,3-Diketone Possessing <i>C</i><sub>2</sub> Symmetry","symmetry was synthesized and utilized in the asymmetric synthesis of guignardone H and I by employing sequential condensation-6π-electrocyclization reactions with the novel 1,3-diketone followed by stereoselective hydrogenation as key steps. Although the synthetic compounds differed from natural guignardone H and I, we realized that the C4-epimers of the proposed structures for guignardone H and I were the actual structures.",10.1021/acs.orglett.9b00486,2019-03-19,0.6535610999144634
Journal of Organic Chemistry,Total Synthesis and Absolute Configuration of Curvularides A-E,"The first total synthesis of curvularides A-E, isolated from a culture broth of the endophytic fungus Curvularia geniculata, is described. The divergent total synthesis reported herein confirmed the absolute configurations of curvularides A-E and supported that these natural products might be obtained from a common biosynthetic pathway. The key steps involved in the synthesis were the diastereoselective hydrogenation of exo-methylene-γ-butyrolactone to α-methyl-γ-butyrolactone, Sharpless kinetic resolution, Sharpless asymmetric epoxidations, and intramolecular and intermolecular epoxide openings.",10.1021/jo301264k,2012-11-02,0.6535529474765114
Journal of Organic Chemistry,Total Synthesis of (±)-Deethylibophyllidine:  Studies of a Fischer Indolization Route and a Successful Approach via a Pummerer Rearrangement/Thionium Ion-Mediated Indole Cyclization,"The total synthesis of (+/-)-deethylibophyllidine is described, proceeding in eight steps from 4-(methoxyphenyl)ethylamine in 5% overall yield (Scheme 6). In terms of sequential annulation, the strategy involves the following operations: E --> DE --> ABDE --> ABCDE (Scheme 1). The key steps in the synthesis are the stereoselective formation of octahydroindol-6-ones by acid treatment of dihydroanisole derivatives, the regioselective Fischer indolization to obtain octahydropyrrolo[3,2-c]carbazoles, and the tandem process consisting of Pummerer rearrangement upon a beta-amino sulfoxide and thionium ion cyclization upon a beta-indole position of a 2,3-disubstituted indole to generate the quaternary spiro center. Attempts to effect the construction of the pentacyclic framework by means of Fischer indolization of the octahydropyrrolo[3,2,1-hi]indol-6-one resulted in failure (Scheme 2).",10.1021/jo960848z,1996-01-01,0.653542336484122
Organic Letters,Stereocontrolled Synthesis of the DE Ring System of the Marine Alkaloid Upenamide,[reaction: see text] A stereocontrolled synthesis of the DE fragment (2) of the marine alkaloid upenamide (1) is described. The synthesis proceeds in 12 steps from caprolactone (10) and 20-25% overall yield.,10.1021/ol051993e,2005-10-15,0.6535097037612247
Tetrahedron,An expeditious route to the synthesis of highly functionalized chiral oxepines from monosaccharides,,10.1016/s0040-4039(98)00324-4,1998-05-01,0.6534466339874959
Organic Process Research & Development,Process Development and Scale-Up of a Novel Route to 8-Aminooctanoic Acid,"A robust and scalable process for the production of 8-aminooctanoic acid has been developed. Starting from commercially available azelaic acid, the target compound was obtained in four steps in a 62% overall yield. The process starts with a Fischer esterification, followed by a highly selective enzymatic hydrolysis of dimethyl azelate to methyl hydrogen azelate. Ammonolysis of the latter using aqueous ammonia and subsequent Hofmann rearrangement yields 8-aminooctanoic acid. The scalability of the process has been demonstrated through the successful production of 25 kg of 8-aminooctanoic acid (5 kg batches). Furthermore, a proof of principle has been demonstrated for a further streamlined process in which the first three steps are telescoped.",10.1021/acs.oprd.5c00109,2025-09-22,0.6534111900659413
Journal of the American Chemical Society,Total Synthesis of Jerangolid D,"A short and convergent synthesis of jerangolid D is described. As key steps, a Blaise reaction is employed to construct the lactone ring, a diastereoselective multicomponent Sakurai condensation leads to the dihydropyran ring, and the skipped diene is assembled using a modified Julia olefination.",10.1021/ja0691728,2007-02-23,0.6533873712971057
Tetrahedron,An efficient organocatalytic route to the atorvastatin side-chain,,10.1016/j.tetlet.2007.09.133,2007-10-26,0.6533839923600819
Organic Letters,Total Synthesis of (+)-Cystothiazole A,"[structure: see text]. The total synthesis of cystothiazole A is described. Key steps of the synthesis include an Evans asymmetric catalytic aldol reaction, which established the required C4-C5 stereochemistry. The [2,4']-bis(thiazole) was obtained applying our methodology of electrophilic activation of amide. Semistabilized Wittig reaction between the phosphonium salt 3 and the aldehyde 2 afforded 1 in nine linear steps and 38% overall yield.",10.1021/ol035600s,2003-10-01,0.6533646310822507
Tetrahedron,New triene synthesis from sorbic acid: two-step synthesis of cis- and trans- galbanolenes,,10.1016/s0040-4039(00)92216-0,1992-04-01,0.6533515295288784
Journal of Organic Chemistry,A Practical Total Synthesis of Globo-H for Use in Anticancer Vaccines,"An improved synthesis of the hexasaccharide MBr1 antigen (globo-H) is reported. Enhanced efficiency in the synthesis was necessary for the scale-up production of globo-H, in order to advance globo-H-based anticancer vaccines to clinical trials. The key features of the improved synthesis include preactivation-based glycosylations and a revised iodosulfonimidation/rearrangement.",10.1021/jo901682p,2009-10-02,0.6533417103218653
Synthesis,Stereoselective Total Synthesis of (±)-Dasycarpidol and (±)-Dasycarpidone,"The protecting-group-free and scalable total syntheses of (±)-dasycarpidol and (±)-dasycarpidone, as well as the formal total synthesis of (±)-uleine, are presented starting from a common tetrahydrocarbazole-fused lactone that is conveniently prepared on multigram scale. The key azocino[4,3- b ]indole skeleton is constructed via the DDQ-mediated dehydrogenative cyclization of a tetrahydrocarbazole derivative possessing an amide side chain. The syntheses of the target natural products are accomplished in high yields and in a few steps by employing readily available conventional reagents.",10.1055/s-0035-1562528,2016-08-16,0.6533416976359467
European Journal of Organic Chemistry,A Concise and Practical Semisynthesis of Ecteinascidin 743 and (–)‐Jorumycin,"Ecteinascidin 743 is an antitumor drug used to treat specific soft‐tissue sarcomas (STS). In this paper, we present a concise and practical semisynthesis of ecteinascidin 743 starting from safracin B. The strategy involves the direct conversion of an aliphatic amino group into an acetoxy group. By this approach, ecteinascidin 743 was synthesized in 14 steps and 1.5 % overall yield. The synthetic approach also provided access to other tetrahydroisoquinoline alkaloids, such as (–)‐jorumycin (a promising anticancer candidate). (–)‐Jorumycin was prepared in six steps and 24.1 % overall yield from safracin B.",10.1002/ejoc.201601409,2016-12-15,0.6533051390894792
Journal of Organic Chemistry,"(+)- and (−)-Mutisianthol: First Total Synthesis, Absolute Configuration, and Antitumor Activity","The first synthesis of the natural product (+)-mutisianthol was accomplished in 11 steps and in 21% overall yield from 2-methylanisole. The synthesis of its enantiomer was also performed in a similar overall yield. The absolute configuration of the sesquiterpene (+)-mutisianthol was assigned as (1S,3R). Key steps in the route are the asymmetric hydrogenation of a nonfunctionalized olefin using chiral iridium catalysts and the ring contraction of 1,2-dihydronaphthalenes using thallium(III) or iodine(III). The target molecules show moderate activity against the human tumor cell lines SF-295, HCT-8, and MDA-MB-435.",10.1021/jo9000405,2009-02-20,0.6533022251668713
Synlett,An Organoiron Approach to the Synthesis of Dihydrodioscorine,All articles of this category A regioselective method for the preparation of 4-alkyl-2-methoxy substituted tricarbonyl(η 5 -cyclohexadienyl)iron(1+) salts 3 is described and applied to the preparation of a key intermediate {methyl 4-[( R )-6-cyano-3-oxo-1-cyclohexenyl] -3-methylbutyrate ( 2 )} for an organoiron route for the synthesis of dihydrodioscorine.,10.1055/s-1992-21331,1992-01-01,0.6532646756255525
Organic Process Research & Development,Process Development of a Novel Anti-Inflammatory Agent. The Regiospecific Bromination of 4‘-Acetylmethanesulfonanilide,"An efficient, practical synthesis of a novel antiinflammatory agent (FK3311, 1 ) which is acceptable environmentally and could be used for pilot plant manufacture is described. Regiospecific bromination of 4‘-acetylmethanesulfonanilide, allowing selective side chain or nuclear halogenation, also has been investigated. Development efforts focused on the optimized Ullmann coupling reaction conditions and the isolation and purification of 1 to give satisfactory quality product (99.8% purity) according to the new and concise synthetic route.",10.1021/op970039x,1998-03-01,0.6532624371089507
Organic Process Research & Development,Development of Large-Scale Routes to Potent GPR119 Receptor Agonists,"Practical and scalable syntheses were developed that were used to prepare multikilogram batches of GSK1292263A ( 1 ) and GSK2041706A ( 15 ), two potent G protein-coupled receptor 119 (GPR119) agonists. Both syntheses employed relatively cheap and readily available starting materials, and both took advantage of an S N Ar synthetic strategy.",10.1021/acs.oprd.6b00157,2016-07-13,0.6532422501840633
Organic Process Research & Development,The Chemical Development of LB71350,An efficient synthesis of the HIV-1 protease inhibitor LB71350 ( 1 ) is described. High diastereoselective epoxidation of the cis -allylic carbamate fragment of (5 S )-[ N -(benzyloxycarbonyl)-amino]- N -[2-methyl-(1 R )-[(phenyl)carbonyl]-propyl]-6-phenylhex-( Z )-enamide ( 16 ) and one-pot preparation of N -[(1-methylethoxy)carbonyl]-3-(methylsulfonyl)- l -valine ( 4 ) are the key features of the synthesis.,10.1021/op034062w,2003-10-03,0.6532118352906798
Tetrahedron,A novel inhibitor of human α-L-fucosidase: Enantioselective synthesis of L-fucoamidrazone,,10.1016/s0040-4039(00)76682-2,1994-06-01,0.6532110850203534
Synthesis,Anticancer Agent Development; 6.<sup>1</sup>Application of the Heterocycle Annulation-Rearrangement Strategy in the Synthesis of a Podophyllotoxin Precursor,"All articles of this category A four-step synthesis of the Bristol-Myers' precursor, ethyl rel -(3 R , 4 R )-6,7-methylenedioxy-1-oxo-4-(3,4,5-trimethoxyphenyl)-1, 2,3,4-tetrahydronaphthalene-3-carboxylate, to (±)-podophyllotoxin is described in 40 % overall yield from ethyl 3,4,5-trimethoxycinnamate. Manganese(III) acetate mediated lactonization and Lewis acid induced heterocyclic rearrangement processes serve as the key steps in the synthesis of this intermediate.",10.1055/s-1991-26444,1991-01-01,0.653204439659171
Organic Letters,Enantioselective Total Synthesis of the Potent Anti-HIV Nucleoside EFdA,"A concise enantioselective total synthesis of 4'-ethynyl-2-fluoro-2'-deoxyadenosine (EFdA), an extremely potent anti-HIV agent, has been accomplished from (R)-glyceraldehyde acetonide in 18% overall yield by a 12-step sequence involving a highly diastereoselective ethynylation of an α-alkoxy ketone intermediate.",10.1021/ol202116k,2011-09-02,0.6531931855293576
Synlett,Synthesis of (+/-)-CurcumeneEther,A 9 step synthesis of (+/-)-curcumene ether is described starting from 5-bromo-2-methyl-2-pentene and 2-amino-5-methylphenol in 7% overall yield using an intramolecular Heck reaction as the key transformation to generate a stereogenic quaternary center.,10.1055/s-2003-40343,2003-06-30,0.6531917216615505
Journal of Organic Chemistry,"Stereoselective Synthesis of PSI-352938: A β-<scp>d</scp>-2′-Deoxy-2′-α-fluoro-2′-β-<i>C-</i>methyl-3′,5′-cyclic Phosphate Nucleotide Prodrug for the Treatment of HCV","PSI-352938 is a novel 2'-deoxy-2'-α-fluoro-2'-β-C-methyl 3',5'-cyclic phosphate nucleotide prodrug currently under investigation for the treatment of hepatitis C virus (HCV) infection. PSI-352938 demonstrated superior characteristics in vitro that include broad genotype coverage, superior resistance profile, and high levels of active triphosphate in vivo in the liver compared to our first and second generation nucleoside inhibitors of this class. Consequently, PSI-352938 was selected for further development and an efficient and scalable synthesis was sought to support clinical development. We report an improved, diastereoselective synthesis of a key 1'-β-nucleoside intermediate 13 via S(N)2 displacement of 1-α-bromo ribofuranose sugar 16 with the potassium salt of 6-chloro-2-amino purine and an efficient method to prepare cis-Rp cyclic phosphate (PSI-352938) in a highly stereoselective manner without any chromatographic purification. The 1-α-bromo sugar 16 was stereospecifically prepared from the corresponding 1-β-lactol in high yield under mild bromination conditions using CBr(4)/PPh(3) (Appel reaction). The desired cis-Rp 3',5'-cyclic phosphate construction was accomplished using isopropyl phosphorodichloridate readily obtained from POCl(3) and isopropyl alcohol. The base combination of Et(3)N/NMI was identified as a key factor for producing PSI-352938 as the major (>95%) diastereomer (cis-Rp) in high yield after the final cyclization step. The current route described in this article was successfully used to produce PSI-352938 on multikilogram scale.",10.1021/jo200060f,2011-04-07,0.653188877743122
Organic Letters,"Application of Enantioselective Sulfur Ylide Epoxidation to a Short Asymmetric Synthesis of Bedaquiline, a Potent Anti-Tuberculosis Drug","A highly selective asymmetric synthesis of a potent anti-TB drug (-)-bedaquiline is accomplished using sulfur ylide asymmetric epoxidation, employing (+)-isothiocineole as an inexpensive and readily available chiral sulfide. Excellent enantioselectivity (er 96:4) and diastereoselectivity (dr 90:10) were obtained for the construction of the key diaryl epoxide, which was subsequently subjected to a highly regioselective ring opening (96:4). The synthesis was completed in nine steps starting from commercially available aldehyde in 8% overall yield.",10.1021/acs.orglett.3c01286,2023-06-07,0.653187626995433
Organic Process Research & Development,"Process Development of Bersacapavir, Part 1: Route Scouting Effort toward a Key Amide Intermediate","In this article, the route scouting effort toward a key secondary amide intermediate in the synthesis of bersacapavir is described. This study relies on the haloform reaction and the reactivity of trichloromethylketone. First, a more classical synthesis route was developed, based on the preparation of a carboxylic acid from the corresponding trichloromethylketone (conventional haloform reaction). The second, and preferred, approach utilized an innovative extension of the haloform reaction, allowing direct coupling between electron-poor aniline and trichloromethylketone. The desired amide intermediate was obtained in high yield and purity via a simple two-step synthesis using cheap and readily available starting materials.",10.1021/acs.oprd.4c00153,2024-07-15,0.6531721520032083
Organic Process Research & Development,Process Research and Development of an NK-1 Receptor Antagonist. Enantioselective Trifluoromethyl Addition to a Ketone in the Preparation of a Chiral Isochroman,"CJ-17,493 ( 4 ) is a chiral NK-1 receptor antagonist. It was first prepared through a diastereoselective crystallization, then through chiral chromatography of a key intermediate, and ultimately via asymmetric synthesis. Multiple routes for the preparation of a key isochroman were demonstrated, and conditions for improved regioselectivity of a Friedel–Crafts acylation were identified. Cesium fluoride was found to be an acceptable initiator for the generation of a nucleophilic trifluoromethyl anion from CF 3 TMS. A cinchonine-derived catalyst was identified for the enantioselective addition of the trifluoromethyl group to the ketone, and it was found that the product of the addition would be converted directly to the isochroman by treatment with t -BuOK. A Duff reaction was used for the formylation, and the resulting aldehyde was coupled to amine 5 to afford CJ-17,493 ( 4 ).",10.1021/op7001886,2007-10-30,0.6531706403999491
Angewandte Chemie International Edition,Total Synthesis of Bafilomycin A<sub>1</sub>,"A convergent synthesis of bafilomycin A1 (see structure) is presented, and relies on the Zn(OTf)2-mediated diastereoselective addition of alkynes to aldehydes. The coupling of a complex enyne with a sensitive aldehyde in the key step, in combination with a novel strategy for a chemoselective trans-reduction of the enyne, establishes an alternative to standard palladium-catalyzed cross-coupling strategies for the formation of 1,3-dienes.",10.1002/anie.200804645,2008-12-09,0.6531679147400996
Journal of Organic Chemistry,Gold-Mediated Synthesis and Functionalization of Chiral Halopyridones,A rapid and efficient one-step halopyridone synthesis has been developed based on gold-catalyzed cyclization of β-amino-ynone intermediates and halodeauration process.,10.1021/jo400827b,2013-07-08,0.6531668972040044
Tetrahedron,"Total synthesis of a glyoxalase I inhibitor and its precursor, (−)-KD16-U1",,10.1016/s0040-4039(97)10559-7,1998-01-01,0.6531645472164848
Tetrahedron,A first and general route to naphthylisoquinoline alkaloids: the total synthesis of O-methyl-tetradehydro-triphyophylline,,10.1016/s0040-4039(01)81225-9,1984-01-01,0.6531400894566622
Angewandte Chemie International Edition,Three Rings in One Step: A Quick Approach to IKD‐8344,"A highly efficient enantioselective total synthesis of the natural antibiotic IKD-8344 is achieved through a convergent route. This route features an otherwise impossible concurrent formation of the THF rings from a linear polyketide precursor through intramolecular O alkylations of mesylates in competition with normally rather facile β elimination and/or α racemization reactions (see scheme, Ms=methanesulfonyl).",10.1002/anie.201201395,2012-04-11,0.6531223333385271
Journal of Organic Chemistry,Synthesis of (−)-Homogalanthamine from Naltrexone,"Acetylcholinesterase inhibitor (-)-homogalanthamine 3 was synthesized from μ opioid antagonist naltrexone (2) in 16% total yield. The synthesis features Grob fragmentation as a key reaction, which was especially accelerated in the presence of 15-crown-5.",10.1021/jo1022487,2011-03-07,0.653095488068495
European Journal of Organic Chemistry,"Absolute Stereochemical Assignment of SCH 71450, a Selective Dopamine D<sub>4</sub> Receptor Antagonist, Through Enantioselective Epimer Synthesis","Abstract The absolute stereochemical assignment of SCH 71450, a selective dopamine D 4 receptor antagonist, has been successfully confirmed through enantioselective epimer synthesis. An allyl substituent on the p ‐hydroxybenzyl group was demonstrated to be an appropriate protecting group for Noyori Ru‐catalyzed asymmetric transfer hydrogenation of the imine derivative. The construction of the sugar moiety involved a β‐glycosylation reaction assisted by neighboring group participation. By comparison with literature data, the absolute stereochemistry at the C‐1 carbon on the tetrahydroisoquinoline core has been assigned the S configuration.",10.1002/ejoc.201300072,2013-03-27,0.6530939865707847
Organic Letters,The First Total Synthesis of (±)-Eremopetasidione,"[figure: see text] The total synthesis of racemic eremopetasidione, a norsesquiterpenoid, has been achieved in nine steps and 30% overall yield starting from creosol (5). Diels-Alder reaction of masked o-benzoquinone 6 and ethyl vinyl ketone and Cope rearrangement of 2-silyloxy-1,5-dienone 3 are the key steps.",10.1021/ol000355n,2000-12-22,0.6530846725439292
Organic Process Research & Development,Development of a Robust Synthesis of Dactolisib on a Commercial Manufacturing Scale,"The development of the robust synthesis of 2-methyl-2-[4-[3-methyl-2-oxo-8-(quinolin-3-yl)-2,3-dihydro-1 H -imidazo[4,5- c ]quinolin-1-yl]-phenyl]propionitrile (dactolisib) on a commercial scale is described. The key step is a Pd-catalyzed Suzuki coupling of 2-[4-(8-bromo-3-methyl-2-oxo-2,3-dihydro-1 H -imidazo[4,5- c ]quinolin-1-yl)-phenyl]-2-methyl-propionitrile to 3-quinoline boronic acid. A special focus is placed on reducing the amount of Pd catalyst used in the Suzuki coupling and purifying the crude drug substance, including removing traces of Pd.",10.1021/acs.oprd.9b00221,2019-08-15,0.653066915060637
Organic Letters,Stereocontrolled Synthesis of the C8–C22 Fragment of Rhizopodin,"A convergent synthesis of the central C8-C22 core of the potent macrolide antibiotic rhizopodin is reported. Notable features of the stereocontrolled approach include an asymmetric reverse prenylation of an alcohol using a method of Krische, a thiazolium catalyzed transformation of an epoxyaldehyde as described by Bode, and a late-stage oxazole formation from advanced intermediates. This route demonstrates the applicability of these methodologies in complex natural product synthesis.",10.1021/ol203130b,2011-12-13,0.6530624654826465
Tetrahedron,A simple synthetic route to -sirenin,,10.1016/s0040-4039(01)98199-7,1970-01-01,0.6530542862078615
Tetrahedron,Addition of dichlorocarbene to aporphinoids: a new route to homoaporphines,,10.1016/s0040-4039(00)98552-6,1985-01-01,0.6530334468744192
Organic Letters,Stereodivergent Total Synthesis of Ethyl Plakortide Z,"positions of the endoperoxide, which are substituted by ethyl groups. The ethyl plakortide Z has the simplest side chain among its congeners and is an excellent target for testing a universal strategy for the synthesis of this subfamily. Accordingly, we have synthesized for the first time a six-membered pla-kortide using asymmetric Enders alkylation, regioselective cyclobutanol oxidative expansion, and peroxycarbenium ion-mediated diastereoselective C-C bond formation as key steps. Preparative HPLC separation of the various diastereomers yielded a pure sample of synthetic ethyl plakortide Z, constituting the first total synthesis. Despite the lack of selectivity inherent in the synthesis of peroxide linkages involving radical reactions, the diastereomer separation step was offset by an efficient synthesis in just 11 steps and 4.2% overall yield.",10.1021/acs.orglett.4c01893,2024-06-27,0.6530239287180065
Journal of Organic Chemistry,"A Synthesis of Elenic Acid, a Topoisomerase II Inhibitor",,,1998-01-01,0.6530176005768342
Tetrahedron,An efficient synthesis of the C1–C14 subunit of (−)-lasonolide A via a target oriented β-C-glycoside formation sequence,,10.1016/j.tetlet.2005.11.156,2005-12-22,0.6530134960279134
Organic Process Research & Development,"Practical Syntheses of Oxindole Derivatives: Chemical Development towards 2-(5-Chloro-2-oxo-2,3-dihydroindol-1-yl)acetamide and (<i>S</i>)-2-(5-Chloro-2-oxo-2,3-dihydroindol-1-yl)propionamide",We describe development of scalable syntheses of novel oxindole-type SV2A ligands with improved potency towards seizure suppression.,10.1021/op800203p,2009-01-30,0.6529792294212933
Organic Letters,"One-Pot Construction of 1-Phenylchromeno[3,4-<i>b</i>]pyrrol-4(3<i>H</i>)-one: Application to Total Synthesis of Ningalin B and a Pyrrolocoumarin-Based Electrochromic Switch","An efficient construction of 1-phenylchromeno[3,4- b]pyrrol-4(3 H)-one via coupling of 1-styrylpyrrolidine and 4-chloro-3-nitrocoumarin as a key step is reported. This reaction is further applied to the total synthesis of the natural product ningalin B in five linear steps with an overall yield of 41.5% and a pyrrolocoumarin-based electrochromic switch.",10.1021/acs.orglett.9b01830,2019-06-24,0.6529733091170846
Journal of Organic Chemistry,"Synthesis of Balsaminone A, a Naturally Occurring Pentacyclic Dinaphthofuran Quinone","A short synthesis of the natural product balsaminone A, a dinaphthofuran quinone, is described. The key steps of the synthesis are base-induced coupling of 1,4-dihydroxy-2-naphthaldehyde with 2,3-dichloronaphthoquinone to give a pentacyclic dinaphthofuran directly, followed by conversion of the aldehyde into the desired methoxy group via the corresponding phenol. The synthesis, in which the structure of a key pentacyclic intermediate is corroborated by X-ray crystallography, confirms the original structural assignment of the natural product.",10.1021/jo201395n,2011-08-29,0.6529538697396027
Synthesis,First and Efficient Synthesis of 14-Aminophenanthroindolizidine Alkaloids,14-Aminophenanthroindolizidine alkaloids and their N-acyl derivatives were prepared by a concise and efficient route ­involving a Parham-type cyclization as the key step.,10.1055/s-0030-1259487,2011-02-24,0.6529278882999481
European Journal of Organic Chemistry,Enantioselective Synthesis of (–)‐Methoxyestrone,"Abstract Enantioselective synthesis of unnatural (–)‐methoxyestrone in 12 steps from the commercially available tetralone based on the formation of a chiral bicyclic intermediate having the A–B steroid ring framework was accomplished. The crucial synthetic step comprised the enantioselective conjugate addition of vinylmagnesium bromide to a chiral imine formed from a trisubstituted cyclic α,β‐unsaturated aldehyde with &gt;98 % ee , giving rise to the stereoselectively substituted building block possessing the A–B steroid rings. Further steps included the construction of the side chain containing the triple bond, and the obtained enyne was subjected to a Pauson–Khand reaction that furnished stereoselectively an intermediate tetracyclic ketone. Further functional group transformations yielded the target compound.",10.1002/ejoc.201100317,2011-05-13,0.6529250932549876
Journal of Organic Chemistry,Selective and Gram-Scale Synthesis of [8]Cycloparaphenylene,"Selective and large-scale synthesis of [8]cycloparaphenylene (CPP) was achieved in seven steps starting from commercially available 4-bromo-4′-hydroxybiphenyl and 4,4′-dibromobiphenyl. The key unsymmetrical tetraring unit, 4-bromophenyl and 4′-bromobiphenyl-substituted cis -1,4-bis(triethylsiloxy)-2,5-cyclohexadiene-1,4-diyl ( 5fA ), was synthesized on an ∼50 g scale by stereoselective cis-addition of 4-bromo-4′-lithiobiphenyl to 4-(4-bromophenyl)-4-hydroxy-2,5-cyclohexadien-1-one, which was synthesized on an ∼100 g scale. Platinum-mediated selective dimerization of the four-ring unit 5fB and subsequent reductive aromatization of the cyclohexadiene-diyl by H 2 SnCl 4 gave 2 g of [8]CPP in 6.6% overall yield (10.2% on small scale).",10.1021/acs.joc.9b02844,2020-01-13,0.6529242753595075
Synlett,Concise Enantiospecific Synthesis of (+)-Calvine,"We report herein an efficient enantiospecific synthesis of (+)-calvine in nine steps from (R)-epichlorohydrine. The convergent synthesis is based on an olefin cross-metathesis (CM) reaction of a chiral homoallylamine and an enone. Subsequent reductive ­cyclization and lactonization of the cis-2,6-disubstituted piperidine intermediate furnished the product in good yield.",10.1055/s-2006-926267,2006-02-06,0.6529104779691317
Synlett,The Triumph of Zinc: A Short and Highly Efficient Synthesis of the Calyculin C<sub>1</sub>-C<sub>9</sub> Tetraene Building Block by Negishi Coupling,"All articles of this category A short and highly efficient synthesis of phosphonate 5 , a key building block of the C 1 -C 9 tetraene fragment of calyculins and calyculinamides, has been achieved. The key step involves a novel, highly chemoselective Negishi coupling with a bismetallic reagent 13 . Negishi coupling - calyculins - polyenes - Stille coupling - palladium-catalyzed cross-coupling",10.1055/s-1999-2979,1999-12-01,0.6528891882663369
Organic Letters,Total Synthesis of the Proposed Structure of Maltepolide C,"The first total synthesis of the proposed structure of cytotoxic macrolide maltepolide C has been achieved via an E-selective intramolecular Heck cyclization as a key step. Other key features of the synthesis are Z-selective Wittig olefination, Sharpless asymmetric dihydroxylation followed by Williamson-type cyclo-etherification, Brown asymmetric allylation, and Noyori reduction of an alkynone. Detailed NMR study confirms the structure and stereochemistry of the synthetic maltepolide C unambiguously. However, the deviation of the spectra of the synthetic maltepolide C from those of the natural maltepolide C indicates a possible error in the original structural assignment.",10.1021/acs.orglett.6b01981,2016-07-29,0.65288848903801
Organic Process Research & Development,"Synthesis of 2‘-<i>O</i>-Benzoyl-3-keto-6-<i>O</i>-propargyl-11,12-carbamoyl Erythromycin A","An efficient and practical synthesis of 2‘- O -benzoyl-3-keto-6- O -propargyl-11,12-carbamoyl erythromycin A ( 4 ) is described. The semisynthetic macrolide was prepared on large scale in seven steps in 38% overall isolated yield from the readily available bis(trimethylsilyloxy) ether of erythromycin A oxime ketal ( 5 ). The chemistry, which required no chromatography, involved selective hydrolysis, alkylation, and hydroxyl protection transformations.",10.1021/op025535m,2002-10-15,0.6528723548316052
Synthesis,"A Short Enantioselective Formal Synthesis of Methyl (S)-(-)-6,8-Dihydroxyoctanoate: A Key Intermediate for the Synthesis of R-(+)-α-Lipoic Acid","All articles of this category A short enantioselective formal synthesis of methyl ( S )-(-)-6,8-dihydroxyoctanoate starting from readily available 2-nitrocyclohexanone using a novel retro-Henry reaction is described. R-(+)-α -lipoic acid - 2-nitrocyclohexanone - retro-Henry reaction",10.1055/s-1996-4380,1996-11-01,0.6528652811816007
Tetrahedron,A synthetic route for the generation of C-7 substituted azepinones,,10.1016/s0040-4039(00)76227-7,1994-02-01,0.6528507073426916
Journal of the American Chemical Society,Synthesis of the WXYZA′ Domain of Maitotoxin,"A synthesis of the WXYZA' domain (7) of the marine neurotoxin maitotoxin (1) is reported. The convergent synthetic strategy involves construction of key building blocks 11 and 12, their coupling, and the elaboration of the resulting ester (10) to the target molecule through a ring-closing metathesis and a hydroxy dithioketal cyclization as the key steps. For the construction of fragment 11, the Noyori reduction/Achmatowicz rearrangement and hydroxy epoxide opening technologies were applied (starting from furfuryl alcohol (13)), whereas for the synthesis of fragment 12, a carbohydrate-based approach was adopted (starting from 2-deoxy-D-ribose (14)). The synthesized WXYZA' domain (7) of maitotoxin (1) exhibited the expected (13)C NMR chemical shifts, supporting the originally assigned structure of the corresponding region of the natural product.",10.1021/ja109533y,2010-12-17,0.6528454541220718
Organic Process Research & Development,A Practical and Efficient Approach to the Preparation of Bioactive Natural Product Wogonin,"A scalable and practical route to wogonin, a bioactive natural product with multiple pharmacological activities which is currently under phase I/II clinical studies, is described. Wogonin was obtained via a four-step process starting from commercially available chrysin and including the Elbs oxidation, benzylation, methylation, and the final debenzylation. The whole procedure gives the target product in a 38% overall yield with >99% purity. Key steps in this process including oxidation and methylation are discussed in detail. The optimized process has been successfully demonstrated on the kilogram scale to support ongoing clinical development of wogonin.",10.1021/acs.oprd.6b00249,2017-01-10,0.652840045042378
Journal of Organic Chemistry,Synthesis of Canthin-4-ones and Isocanthin-4-ones via B Ring Construction,"High Resolution Image Download MS PowerPoint Slide Canthin-4-one is synthesized via a six-step procedure starting from commercially available 3-amino-4-bromopyridine in 26% overall yield. 3-Amino-4-bromopyridine is initially converted to 8-bromo-1,5-naphthyridin-4(1 H )-one. O-Methylation, intermolecular Pd-catalyzed C–C coupling, and demethylation afford the key intermediate, 8-(2-chlorophenyl)-1,5-naphthyridin-4(1 H )-one, for which intramolecular C–N coupling completes the synthesis of the canthin-4-one skeleton. Ten canthin-4-one analogues were prepared in addition to the parent compound. With minor modifications, the synthesis also applies to the synthesis of two series of isocanthin-4-ones.",10.1021/acs.joc.4c00440,2024-04-24,0.6528241868876978
Tetrahedron,An Enantioselective Route Towards Clerodane Diterpenoids,,10.1016/s0040-4039(00)78801-0,1991-06-01,0.6528168473785279
Angewandte Chemie International Edition,Total Synthesis of (+)‐Cornexistin,"Herein, we describe the first total synthesis of (+)-cornexistin as well as its 8-epi-isomer starting from malic acid. The robust and scalable route features a Nozaki-Hiyama-Kishi reaction, an auxiliary-controlled syn-Evans-aldol reaction, and a highly efficient intramolecular alkylation to form the nine-membered carbocycle. The delicate maleic anhydride moiety of the nonadride skeleton was constructed from a β-keto nitrile. The developed route enabled the synthesis of 165 mg (+)-cornexistin.",10.1002/anie.202008158,2020-06-18,0.6528142940274503
Journal of Organic Chemistry,"The Chiron Approach to (3<i>R</i>,3<i>aS</i>,6<i>aR</i>)-Hexahydrofuro[2,3-<i>b</i>]furan-3-ol, a Key Subunit of HIV-1 Protease Inhibitor Drug, Darunavir","We describe an enantioselective synthesis of (3 R,3 aS,6 aR )-hexahydrofuro[2,3- b ]furan-3-ol which is a key subunit of darunavir, a widely used HIV-1 protease inhibitor drug for the treatment of HIV/AIDS patients. The synthesis was achieved in optically pure form utilizing commercially available sugar derivatives as the starting material. The key steps involve a highly stereoselective substrate-controlled hydrogenation, a Lewis acid catalyzed anomeric reduction of a 1,2- O -isopropylidene-protected glycofuranoside, and a Baeyer–Villiger oxidation of a tetrahydrofuranyl-2-aldehyde derivative. This optically active ligand alcohol was converted to darunavir efficiently.",10.1021/acs.joc.0c02396,2020-12-03,0.6527973481060043
Journal of Organic Chemistry,Synthesis of Ovalicin Starting from <scp>d</scp>-Mannose,"[reaction: see text] A new synthesis of epoxyketone 22 is described that is a key intermediate in Barton's synthesis of ovalicin (2), a powerful anti-angiogenetic inhibitor. The key process for the construction of 22 was ring-closing metathesis of olefins 11 and 12 obtained from 2,3:5,6-di-O-isopropylidene-alpha-D-mannofuranose (4) and regioselective desilylation of tri-TES ether 19. Furthermore, an alternative stereoselective route from 22 into 2 has also been developed, and the overall yield of 2 from 4 was 10.0%.",10.1021/jo051686m,2005-10-20,0.6527834538809857
Synlett,A Synthesis of Demethyl Mycosporulone and its C-6 Epimer,Demethyl mycosporulone was synthesized from the methyl ester of dihydro anisic acid in six steps. The key steps included an aldol/oxidation sequence and the formation of the exomethylene group by dehydration using Burgess salt.,10.1055/s-2003-36232,2002-01-01,0.6527639040129755
Synthesis,Asymmetric Synthesis of Jaspine B (Pachastrissamine) via an Organocatalytic Aldol Reaction as Key Step,"The asymmetric synthesis of jaspine B (pachastrissamine) using a (R)-proline-catalyzed enantioselective aldol reaction as key step is described. Jaspine B was synthesized from the commercially available and inexpensive 1-pentadecanal and the dihydroxyacetone equivalent 2,2-dimethyl-1,3-dioxan-5-one in nine steps, good overall yield (23.6%) and excellent stereoselectivity (de >98%, ee = 95%).",10.1055/s-2008-1067142,2008-06-18,0.6527523358310636
Journal of the American Chemical Society,Total Synthesis and Absolute Stereochemical Assignment of (−)-Communesin F,"A concise asymmetric total synthesis of (-)-communesin F (∼6% overall yield in the longest linear sequence of 19 steps) is described. It features an unprecedented intramolecular oxidative coupling strategy for the elaboration of the requisite spiro-fused indoline moiety. Other notable elements are the use of TBS-protected (S)-phenylglycinol as a chiral auxiliary to induce the asymmetric formation of the spiro-fused indoline part, the mesylate-mediated formation of its G ring, and the introduction of the A ring at the final stage via intramolecular Staudinger reaction. This intramolecular Staudinger reaction proceeded smoothly at 80 °C, providing an additional example illustrating that twisted amides are more reactive than simple amides. Along with the total synthesis, we were able to assign the absolute configuration of natural communesin F as 6R,7R,8R,9S,11R.",10.1021/ja106739g,2010-09-02,0.6527438067855104
Journal of the American Chemical Society,11-Step Total Synthesis of (−)-Maoecrystal V,"An expedient, practical, and enantioselective route to the highly congested ent-kaurane diterpene maoecrystal V is presented. This route, which has been several years in the making, is loosely modeled after a key pinacol shift in the proposed biosynthesis. Only 11 steps, many of which are strategic in that they build key skeletal bonds and incorporate critical functionalities, are required to access (-)-maoecrystal V. Several unique and unexpected maneuvers are featured in this potentially scalable pathway. Reevaluation of the biological activity calls into question the initial exuberance surrounding this natural product.",10.1021/jacs.6b06623,2016-07-26,0.6527391461411127
Synthesis,Synthesis of Insect Antifeedants Related to Azadiradione,"All articles of this category An efficient synthesis of a model insect antifeedant based on the C, D and E rings of the limonoid azadiradione has been developed. (8 steps ≥ 18% overall yield). The key steps were an electrocyclization induced by acids 4 5 and a dyotropic rearrangement from epoxide 7 to ketone 8 . synthesis - antifeedant - limonoids - azadiradione - cationic electrocyclization",10.1055/s-1997-1365,1997-12-01,0.6527369112160183
Angewandte Chemie International Edition,Total Synthesis of (−)‐Virginiamycin M<sub>2</sub>,Has a nice ring to it: A concise and modular total synthesis of the naturally occurring antibiotic virginiamycin M2 is described. A Barbier-type cyclization was used to close the 23-membered macrocycle and deliver virginiamycin M2 in 19 steps from a chiral organosilane.,10.1002/anie.201002220,2010-07-20,0.6527325663210866
Journal of Organic Chemistry,Diastereoselective Total Synthesis of (−)-Galiellalactone,"An enantioselective total synthesis of (-)-galiellalactone has been accomplished. The key features of the synthesis involve the highly stereoselective construction of the cis-trisubstituted cyclopentane intermediate by a Pd(0)-catalyzed cyclization, the stereospecific introduction of an angular hydroxyl group by Riley oxidation, and the efficient construction of the tricyclic system of (-)-galiellalactone via a combination of diastereoselective Hosomi-Sakurai crotylation and ring-closing metathesis (RCM).",10.1021/acs.joc.5b02121,2015-11-06,0.6526949218930546
Organic Process Research & Development,Process Development Overcomes a Challenging Pd-Catalyzed C–N Coupling for the Synthesis of RORc Inhibitor <b>GDC-0022</b>,"Process development for a multi-kilogram-scale synthesis of GDC-0022, an inhibitor of retinoic acid receptor-related orphan receptor γ (RORc), is described. Delivery of the active pharmaceutical ingredient (API) relied on diastereoselective preparation of a six-membered sultam building block, as well as execution of its benzylation under heterogeneous conditions. Investigation and optimization of a challenging late-stage palladium-catalyzed C–N coupling of a bicyclic amine were likewise central to synthetic efforts. Understanding of this key reaction, as well as the development of API salt forms and isolations, ultimately enabled a successful reaction at 8.0 kg scale, utilizing 1.0 mol % XantPhos–Pd–G2 as precatalyst and, in turn, preparation of >5.0 kg of GDC-0022 tosylate salt for preclinical needs.",10.1021/acs.oprd.0c00012,2020-03-30,0.6526912998693745
Organic Letters,Total Synthesis of Mevashuntin,"The total synthesis of (±)-mevashuntin, a structurally unique naturally occurring pyrano-naphthoquinone-thiazolone, is described. The route is centered upon a late stage regioselective Diels-Alder reaction between two highly functionalized components, as well as an improved protocol for the one pot synthesis of benzothiazolones from ortho-bromoaryl isothiocyanates. The strategy results in a highly convergent route, providing access to the natural product in 11 steps from 3-(4-methoxyphenoxy)propanol and confirming its relative stereochemistry.",10.1021/ol300221e,2012-02-27,0.6526835490149543
Journal of Organic Chemistry,A Stereoselective Route to Hydroxyethylamine Dipeptide Isosteres,"An efficient synthesis of stereodefined hydroxyethylamine dipeptide isosteres has been developed, utilizing a syn-selective Grignard addition and reductive amination as the key reactions.",10.1021/jo001072b,2000-10-07,0.6526564213182122
Organic Process Research & Development,Process Development and Crystallization in Oiling-Out System of a Novel Topical Antiandrogen,"High Resolution Image Download MS PowerPoint Slide An efficient route to ( S )- N -(2-bromo-6-methoxypyridin-4-yl)-2-hydroxy-2,4-dimethylpentanamide 1, a new topical antiandrogen, is described. The target compound has been manufactured on kilogram scale with an overall yield of 25% (HPLC purity 98.8% and >99% ee ) from citrazinic acid. The key amide coupling between aminopyridine 4 and α-hydroxy-acid 6 was performed using a temporary protecting group to facilitate the acyl chloride formation. Aminopyridine 4 was manufactured from commercially available citrazinic acid via dibromide formation using phosphorus(V) oxybromide followed by mono S N Ar reaction with sodium methoxide and a final Hofmann rearrangement. Enantiopure α-hydroxy-acid 6 was obtained using an enantioselective cyanosilylation followed by salt resolution with ( S )-α-methyl benzylamine. The absolute configuration of compound 1 was determined with anomalous scattering and the final crystallization of API was performed after seeding a liquid–liquid mixture below the monotectic temperature and afforded a crystalline powder presenting a “desert rose” shape clusters.",10.1021/acs.oprd.6b00392,2016-12-21,0.6526466665126215
Journal of Organic Chemistry,Convergent Synthesis of Naphthylisoquinoline Alkaloids:  Total Synthesis of (+)-<i>O</i>-Methylancistrocline,"A highly convergent synthesis of the methyl ether derivative 2a of the naphthylisoquinoline alkaloid ancistrocline (2) is described. The key step involves a stereoselective biaryl coupling between the chiral oxazoline 3 and the Grignard reagent 4 derived from the optically active tetrahydroisoquinoline 8. The atropisomeric mixture was then converted to the separable acetamides 11 and 12, which were obtained in a ratio of 16:84 and an overall yield of 32% for the three steps. The major atropisomer 12 was then converted into O-methylancistrocline (2a), which was identical to a semisynthetic sample derived from the related alkaloid ancistrocladinine (14).",10.1021/jo9607119,1996-01-01,0.6526377131053492
Synlett,Asymmetric Total Synthesis of Attenol A and B,"The asymmetric total synthesis of attenol A (1) and B (2), which possess challenging structures and an interesting biological activity, was accomplished in a convergent and highly stereo­selective manner (de, ee ≥ 96%) with good overall yield. The short total synthesis is based on asymmetric alkylations of SAMP-hydrazones as well as a Sharpless asymmetric dihydroxylation as key steps.",10.1055/s-2003-42071,2003-01-01,0.6526195080741101
Synthesis,The First Total Synthesis of Kynapcin-24 by Palladium Catalysis,"The synthesis of kynapcin-24, which can be isolated from the Korean mushroom Polyozellus multiflex Murr, is achieved in 12% overall yield from commercially available 3,4-dihydroxybenzaldehyde by a route in which the longest linear sequence is only 14 steps. The key transformations in the synthesis are copper-mediated and palladium-catalyzed coupling reactions of the iodide 3-iodo-5,6-diisopropoxy-2-[(tetrahydropyran-2-yloxy)methyl]benzofuran with the corresponding stannane 5,6-diisopropoxy-2-[(tetrahydropyran-2-yloxy)methyl]-3-(tributylstannyl)benzofuran, and a 5-endo-dig iodocyclization of a (hydroxyphenyl)propargyl ether.",10.1055/s-0028-1087998,2009-03-06,0.6526187025480736
Organic Process Research & Development,"Development of a Robust Manufacturing Route for Molnupiravir, an Antiviral for the Treatment of COVID-19","Herein is described the development of a large-scale manufacturing process for molnupiravir, an orally dosed antiviral that was recently demonstrated to be efficacious for the treatment of patients with COVID-19. The yield, robustness, and efficiency of each of the five steps were improved, ultimately culminating in a 1.6-fold improvement in overall yield and a dramatic increase in the overall throughput compared to the baseline process.",10.1021/acs.oprd.1c00400,2021-12-10,0.6525837832852481
Organic Process Research & Development,An Improved and Scalable Process for the Synthesis of Ezetimibe: An Antihypercholesterolemia Drug,"An efficient, cost-effective and large-scale synthesis of ezetimibe 1, an antihypercholesterolemia drug, is described. Chiral oxazolidinone chemistry was used to fix the required stereochemistry of the β-lactam ring, and the chiral oxazaborolidine chemistry was used to fix the hydroxyl group stereochemistry. The synthesis significantly lowers the cost and provides easy access to ezetimibe on large scale.",10.1021/op900039z,2009-08-14,0.6525826120919075
European Journal of Organic Chemistry,"Asymmetric Synthesis of 3,4‐Disubstituted Proline Derivatives: Application in Synthesis of Hepatitis C Virus Protease Inhibitor Telaprevir","Abstract A practical asymmetric synthesis of 3,4‐disubstituted proline derivatives has been realized with high stereoselectivity and moderate yield. The key steps involved are desymmetric ring‐opening reaction of commercially available anhydrides, intramolecular Strecker reaction and thermodynamically controlled cyanide hydrolysis. Based on this methodology, the synthesis of HCV protease inhibitor Telaprevir was achieved.",10.1002/ejoc.201403069,2014-10-31,0.6525707751898568
Journal of Organic Chemistry,"First Diastereoselective Synthesis of (−)-Methyl Thyrsiflorin A, (−)-Methyl Thyrsiflorin B Acetate, and (−)-Thyrsiflorin C","An efficient procedure for the synthesis of scopadulan diterpenes, using (+)-podocarp-8(14)-en-13-one 13 as starting material, is reported. This procedure has been used for the diastereoselective synthesis of (-)-methyl thyrsiflorin A (8), (-)-methyl thyrsiflorin B acetate (9), and (-)-thyrsiflorin C (7). Key steps in our strategy are the intramolecular cyclopropanation of diazoketone 19 and the regioselective cleavage of the cyclopropane ring.",10.1021/jo991561f,2000-01-20,0.6525447074951248
Journal of the American Chemical Society,Total Synthesis of Bryostatin 16 Using a Pd-Catalyzed Diyne Coupling as Macrocyclization Method and Synthesis of C20-<i>epi</i>-Bryostatin 7 as a Potent Anticancer Agent,"Asymmetric total synthesis of bryostatin 16 was achieved in 26 steps in the longest linear sequence and in 39 total steps from aldehyde 10. A Pd-catalyzed alkyne-alkyne coupling was employed for the first time as a macrocyclization method in a natural product synthesis. A route to convert bryostatin 16 to a new family of bryostatin analogues was developed. Toward this end, 20-epi-bryostatin 7 was synthesized from a bryostatin 16-like intermediate; the key step involves a Re-catalyzed epoxidation/ring-opening reaction. Preliminary biological studies indicated that this new analogue exhibits nanomolar anti-cancer activity against several cancer cell lines.",10.1021/ja105129p,2010-11-02,0.652544394062361
Organic Letters,Methoxypyridines in the Synthesis of <i>Lycopodium</i> Alkaloids: Total Synthesis of (±)-Lycoposerramine R,"A methoxypyridine serves as a masked pyridone in a concise synthesis of the Lycopodium alkaloid lycoposerramine R, which has been prepared for the first time. The key step of the synthesis is the use of an Eschenmoser Claisen rearrangement to forge a key quaternary carbon center.",10.1021/ol100823t,2010-05-04,0.6525332915932073
European Journal of Organic Chemistry,Total Synthesis of the Antifungal Natural Product Mollisin,"Abstract Mollisin, a bioactive polyketide secondary metabolite of the fungus Mollisia caesia , was synthesized in nine linear steps from commercially available 2,6‐dimethyl‐γ‐pyrone. A key transformation in this first total synthesis of mollisin was the ipso substitution of an arylstannane, which permitted the otherwise cumbersome introduction of the characteristic dichloroacetyl moiety. The fungal fungicide was obtained in an overall yield of 9 %.",10.1002/ejoc.201301088,2013-08-23,0.6525087564402582
Tetrahedron,Total synthesis of (+)-mesembrine by asymmetric synthesis with amino acid,,10.1016/s0040-4039(01)96647-x,1971-01-01,0.6524796612616443
Tetrahedron,A two step synthesis of the new “octacyclam” and some other octaazacycloalkanes via reduction of tetraamide intermediates,,10.1016/s0040-4039(98)80024-5,1999-01-01,0.6524776313220636
Organic Letters,"Concise Unified Access to (−)-8-Deoxy-13-dehydroserratinine, (+)-Fawcettimine, (+)-Fawcettidine, and (−)-8-Deoxyserratinine Using a Direct Intramolecular Reductive Coupling","A short, scalable, and collective total synthesis of four fawcettimine-type Lycopodium alkaloids in eight or nine steps is disclosed. A dense multi-small-ring spiro -α-aminocyclopentanone successfully served as the key intermediate, which was directly accessed by a LiDBB-mediated intramolecular reductive coupling of the aliphatic imine and an ester-carbonyl. Compared to those that employ classical Heathcock intermediate(s) containing a nine-membered ring, the new strategy shows the significant improvement of the synthetic step and redox economies as well as excellent stereochemical control.",10.1021/acs.orglett.1c00977,2021-04-23,0.6524761845396198
Tetrahedron,"A concise, efficient route to fumitremorgins",,10.1016/s0040-4039(00)01899-2,2001-01-01,0.6524487838748175
Organic Letters,Synthetic Studies toward Gambierol. Convergent Synthesis of the Octacyclic Polyether Core,"[structure: see text]. A convergent synthetic route to the octacyclic polyether core of gambierol, a marine polycyclic ether toxin, has been developed. The synthesis involves construction of two fragments representing the ABC and EFGH ring systems followed by their coupling via a B-alkyl Suzuki reaction.",10.1021/ol0166597,2001-10-10,0.6524455757435761
Tetrahedron,A novel and efficient total synthesis of (±)-physostigmine,,10.1016/j.tetlet.2009.03.012,2009-03-10,0.6524420164917143
Tetrahedron,A novel and efficient total synthesis of shikonin,,10.1016/j.tetlet.2012.05.078,2012-05-26,0.6524420164917143
Synthesis,"A Novel Route for the Synthesis of 3,4-Dihydro-1<i>H</i>-2-benzopyrans and 1,3,4,5-Tetrahydro-2-benzoxepins",,10.1055/s-1983-30443,1983-01-01,0.6524320898560211
Journal of Organic Chemistry,"Dihydropyrromethenones by Pd(0)-Mediated Coupling of Iodopyrroles and Acetylenic Amides. Synthesis of the A,B-Ring Segment of Phytochrome","Dihydropyrromethenone derivative 32b, which constitutes the A,B-ring segment of phytochrome (6), has been prepared in enantiomerically pure form beginning with acetylenic amide 47b and iodopyrrole 27. The key steps involved the TBAF-catalyzed 5-exo-dig cyclization of the acetylenic pyrrole 48b, followed by thia-Mitsunobu inversion of the resulting alcohol derivative 31b.",10.1021/jo970289b,1997-05-01,0.6524139683727196
Organic Process Research & Development,A Tandem Ring Closure and Nitrobenzene Reduction with Sulfide Provides an Improved Route to an Important Intermediate for the Anti-Tuberculosis Drug Candidate Sutezolid,"High Resolution Image Download MS PowerPoint Slide Sutezolid is an in-development thiomorpholine derivative of the FDA-approved tuberculosis (TB) treatment linezolid. Current synthetic routes for preparing sutezolid start with thiomorpholine as a key structural building block; unfortunately, this material was identified as a major cost driver for the API, which will limit the potential uptake of this treatment in lower income regions. In this work, an alternative, lower-cost synthetic strategy to a known p -phenylenediamine intermediate to sutezolid has been demonstrated. The key step in this process is the construction of the thiomorpholine ring by a nucleophilic sulfide ring closure on an activated bis(2-hydroxyethyl)-functionalized aniline, which was in turn made by reaction of 3,4-difluoronitrobenzene and diethanolamine. This sulfide treatment has the added benefit of affecting a Zinin reduction of the nitro functional group, which alleviates the need for the transition metal reduction used in previous routes. After optimization, this key reaction was able to provide the desired aniline intermediate in yields between 65 and 80% and, after a standard charcoal treatment, purity of >94%. Initial demonstrations of the full 3-step strategy were successfully conducted on scales up to 100 g with overall yields of 53–68%. This preliminary work will serve as the foundation for a broader low-cost redesign of the sutezolid synthetic process.",10.1021/acs.oprd.4c00014,2024-03-27,0.6524043327753788
Journal of the American Chemical Society,Development of a Convergent Entry to the Diazofluorene Antitumor Antibiotics: Enantioselective Synthesis of Kinamycin F,"We describe a 12-step enantioselective synthetic route to the complex anticancer antimicrobial agent kinamycin F (3). Key to the success of the route was the development of a three-step sequence for construction of the diazonapthoquinone (diazofluorene, blue in structure 3) function of the natural product. This sequence comprises fluoride-mediated coupling of a beta-(trimethylsilylmethyl)-cyclohexenone and halonapthoquinone, palladium-mediated cyclization to construct the tetracyclic scaffold of the natural product, and mild diazo-transfer to a complex cyclopentadiene to introduce the diazo function. Ortho-quinone methide intermediates, formed by reduction and loss of dinitrogen from 3, have been postulated to form in vivo, and our approach provides a straightforward synthetic pathway to such compounds.",10.1021/ja910769j,2010-02-08,0.6523696977800523
Journal of Organic Chemistry,Novel Alternative for the N<i>−</i>N Bond Formation through a PIFA-Mediated Oxidative Cyclization and Its Application to the Synthesis of Indazol-3-ones,"The synthesis of a series of N,N'-disubstituted indazolone derivatives starting from methyl anthranilates is presented. This general approach features a novel and easy way for access to the target N-heterocycles by formation of a new N-N single bond. The key cyclization step embraces the formation of an N-acylnitrenium intermediate, mediated by the hypervalent iodine reagent PIFA, and its succeeding intramolecular trapping by the amine moiety under rather mild experimental conditions.",10.1021/jo060070+,2006-03-21,0.6523673979898605
Journal of Organic Chemistry,Total Synthesis of the Labdane Diterpenes Galanal A and B from Geraniol,"The first total synthesis of galanal A and B has been achieved from naturally occurring geraniol. Key steps in this synthesis are the use of a Lewis acid assisted chiral Brønsted acid (chiral LBA) mediated cationic polyene cyclization and a titanocene-mediated radical cyclization for the asymmetric assembly of the ""AB"" ring and the construction of the all-carbon quaternary center at the junction of the ""BC"" ring, respectively.",10.1021/acs.joc.6b02766,2016-12-30,0.6523441007766771
Angewandte Chemie International Edition,A Cascade Strategy Enables a Total Synthesis of (−)‐Gephyrotoxin,"A concise and efficient synthesis of (-)-gephyrotoxin from L-pyroglutaminol has been realized. The key step in this approach is a diastereoselective intramolecular enamine/Michael cascade reaction that forms two rings and two stereocenters and generates a stable tricyclic iminium cation. A hydroxy-directed reduction of this intermediate plays a key role in establishing the required cis-decahydroquinoline ring system, enabling the total synthesis of (-)-gephyrotoxin in nine steps and 14% overall yield. The absolute configuration of the synthetic material was confirmed by single-crystal X-ray diffraction and is consistent with the structure originally proposed for material isolated from the natural source.",10.1002/anie.201409038,2014-10-16,0.6523145455263022
Tetrahedron,A new route to branched-chain sugars by -alkylation of methyl glycopyranosiduloses,,10.1016/s0040-4039(00)89534-9,1968-01-01,0.6523035507004813
Journal of Organic Chemistry,A General Route toward the Synthesis of the Cladiellin Skeleton Utilizing a SmI<sub>2</sub>-Mediated Cyclization,"An efficient synthesis of the cladiellin skeleton is reported utilizing methods that were previously developed in this laboratory. The approach is based on a SmI(2)-mediated cyclization reaction for the construction of the oxacyclononane unit. A [4 + 3] annulation strategy was used to create the octahydroisobenzofuran moiety. This route provides the cladiellin skeleton in only 14 steps without the use of protecting groups. The present approach also enabled the synthesis of the 3,7-diastereomer of the natural product polyanthellin A.",10.1021/jo052290d,2006-01-04,0.6522717944006976
European Journal of Organic Chemistry,A Concise Synthesis of the Key Tetrahydrofuran Moieties of Caruifolin A and EBC‐342,A common strategy for the concise synthesis of the key tetrahydrofuran moieties of caruifolin A and EBC‐342 is presented. Asymmetric dihydroxylation and intramolecular S N 2‐cyclization are key strategic reactions for the synthesis of the furan fragments.,10.1002/ejoc.202000513,2020-05-12,0.6522703666162927
Synthesis,Synthesis of<i>N</i>-<i>t</i>-Boc-L-<i>a</i>-aminoadipic Acid 1-<i>t</i>-Butyl 6-Ethyl Ester from L-Aspartic Acid: A New Route to L-a-Aminoadipic Acid,,10.1055/s-1982-29692,1982-01-01,0.6522662622070222
Organic Letters,Total Synthesis of the Hsp90 Inhibitor Geldanamycin,"An enantioselective synthesis of the Hsp90 inhibitor geldanamycin was achieved in 20 linear steps and 2.0% overall yield from 2-methoxyhydroquinone. The synthesis is highlighted by a regio- and stereoselective hydroboration reaction; a Sc(OTf)(3)/Et(3)SiH-mediated pyran ring-opening reaction; an enantioselective crotylation to simultaneously install the C8-C9 (E) -trisubstituted olefin, the C10 and C11 stereocenters; a chelation-controlled asymmetric metallated acetylide addition; and an intramolecular copper(I)-mediated aryl amidation reaction to close the 19-membered macrolactam.",10.1021/ol800749w,2008-05-20,0.6522574339407671
Organic Process Research & Development,"Regioselective Synthesis of 2,6-Dimethyltetralin:  Key Precursor to 2,6-Dimethylnaphthalene","A novel regioselective synthesis for 2,6-dimethyltetralin (2,6-DMT), a key precursor to 2,6-dimethylnaphthalene (2,6-DMN), is described. The synthesis comprises the following three steps; the Heck reaction between commercially available 4-bromotoluene and 3-methyl-3-buten-1-ol, the catalytic reduction of the coupling products, and the acid-catalyzed cyclization of the alcohol intermediate. The process has an advantage over the established processes in that 2,6-DMT is obtained as the only isomer, and the isomerization and/or the complicated separation and purification steps are not required to produce pure 2,6-DMT. 2,6-DMN could be also obtained as a major product depending on the cyclization conditions.",10.1021/op050072g,2005-09-13,0.6522535366857766
Tetrahedron,A short synthetic route to the tricyclic guanidinium core of the batzelladine alkaloids,,10.1016/0040-4039(96)01523-7,1996-09-01,0.6522511235905709
Synthesis,A Novel Asymmetric Synthesis of (+)-Deoxytylophorinine,"A novel asymmetric synthesis of a phenanthroindolizidine alkaloid, (+)-deoxytylophorinine, is reported, which uses a chiral nickel(II) complex of a glycine Schiff base to synthesize a substituted ( R )-3-phenanthrylalanine as a key intermediate and Meldrum’s acid to construct the E ring.",10.1055/s-0034-1380137,2015-03-04,0.6522499690170158
Synlett,An Efficient Synthesis of (±)-Isohinokinin from the Acyclic Ester Precursor,All articles of this category A stereoselective approach to the synthesis of (±) Isohinokinin has been developed in which the key step is the construction of the γ-butyrolactone by PdCl 2 (PhCN) 2 catalyzed cyclization of the easily available acyclic 2-alkenyl 2-alkynoate in the presence of CuCl 2 .,10.1055/s-1993-22352,1993-01-01,0.6522281100790781
Journal of Organic Chemistry,Application of the EF and GH Fragments to the Synthesis of Idraparinux,"A novel total synthesis of fully protected idraparinux has been achieved. A short and efficient protocol for the synthesis of the EF fragment of idraparinux and its C5'-epi analogue (GH unit) has been developed. The same cellobiose unit was transformed in 14 steps into the fully protected EF and GH disaccharide fragments. The key step of this approach is an epimerization of C5 by an elimination-addition sequence leading to l-ido disaccharide (GH unit) with a total yield of 24% (36% for the EF fragment). 1,6-Anhydro ring opening gave suitable substrates for efficient synthesis of fully protected idraparinux. The fully protected antithrombotic pentasaccharide idraparinux was synthesized in 23 steps for the longest linear route, with a 1.7% overall yield from d-cellobiose and d-glucose.",10.1021/acs.joc.7b02497,2017-10-31,0.652221274740132
Organic Process Research & Development,Process Development and Good Manufacturing Practice Production of a Tyrosinase Inhibitor via Titanium-Mediated Coupling between Unprotected Resorcinols and Ketones,"High Resolution Image Download MS PowerPoint Slide A concise and economically attractive process for the synthesis of a novel tyrosinase inhibitor has been developed and implemented on a multikilogram scale under GMP. A major achievement to the success of the process is the development of a direct coupling between free resorcinol and ketone. First developed under basic conditions, this coupling has been turned to a novel titanium(IV) mediated process allowing good selectivity, easy isolation, and high atom efficiency. Other key steps feature an alkene reduction by palladium catalyzed transfer hydrogenation and a urea formation using N,N ′-disuccinimidyl carbonate as the carbonyl source. This route allowed us to produce kilogram batches of the candidate to support preclinical and clinical studies.",10.1021/acs.oprd.7b00036,2017-03-20,0.6521996136165151
European Journal of Organic Chemistry,Synthesis of Melithiazol B and Related Compounds via Oxidative Degradation of Myxothiazol A and Z,"The synthesis of melithiazol B (4) has been accomplished in five steps and 19% overall yield starting from myxothiazol A (1). Key steps include the conversion of the amide into the methyl ester 4, oxygenation to hydroperoxides 7 and 9, and subsequent Hock cleavage to ketones 11 and 12, followed by a Wittig reaction to give 4 and 13. The biological activities of intermediates, melithiazol B and derivatives thereof are compared.",10.1002/(sici)1099-0690(200004)2000:8<1497::aid-ejoc1497>3.0.co;2-8,2000-04-01,0.6521634629337847
Angewandte Chemie International Edition,Total Synthesis of (−)‐Merochlorin A,"The first asymmetric total synthesis of the meroterpenoid (-)-merochlorin A is described. The route features enantiospecific gold-catalyzed tandem 1,3-acyloxy migration/Nazarov/aldol reaction sequence to furnish the bicyclo[3.3.0]octane core in a single step from a linear propargylic 1,3-enyne aldehyde. After completion of the central skeleton by reductive enol lactone rearrangement, late stage Diels-Alder cycloaddition/aromatization sequence installed the resorcinol. An additional salient feature of the synthesis is the assignment of the absolute configuration, which had not been determined previously.",10.1002/anie.201813090,2018-12-21,0.6521592653556619
Synthesis,A Practical Gram-Scale Synthesis of Acrylohydroxamic Acid,"Acrylohydroxamic acid, which is a useful monomer for the preparation of polymeric materials, has been prepared in a straightforward, two-step synthesis from readily available starting materials. The key steps are coupling of acrylic acid with O-tetrahydropyranylhydroxyl amine to provide protection of the hydroxylamine functionality, followed by acid cleavage of the protecting group.",10.1055/s-0036-1589103,2017-08-30,0.6521589827510076
Journal of Organic Chemistry,Asymmetric Total Synthesis of the Caspase-1 Inhibitor (−)-Berkeleyamide A,"The asymmetric total synthesis of (-)-berkeleyamide A (1), a naturally occurring caspase-1 inhibitor, has been achieved by employing Evans' syn-aldol reaction of N-acyl-(4R)-benzyl oxazolidin-2-one 3 as the key step.",10.1021/jo1001033,2010-03-31,0.6521433670469262
Tetrahedron,The first total synthesis of novel human chymase inhibitor SPF32629A,,10.1016/j.tetlet.2008.08.048,2008-08-20,0.6521406135909551
Journal of Organic Chemistry,Asymmetric Total Synthesis of (+)-Winchinine B,"The first asymmetric total synthesis of aspidosperma alkaloid (+)-winchinine B was achieved in 12 steps from commercially available materials. A new synthetic strategy which features an efficient aza-Michael addition, a ruthenium-catalyzed transfer dehydrogenation, and an intramolecular palladium-catalyzed oxidative coupling was adopted to install the ABC tricycle system. A one-pot process involving carbonyl reduction/iminium formation/intramolecular conjugate addition developed by our group was utilized to construct the D ring moiety.",10.1021/acs.joc.9b02462,2019-10-24,0.6521156292825532
European Journal of Organic Chemistry,Total Synthesis of Marine Sesquiterpene Quinones (+)‐Cyclospongiaquinone‐1 and (–)‐Dehydrocyclospongiaquinone‐1 with a Tetracyclic Benzo[<i>a</i>]xanthene Skeleton,"Two marine sesquiterpene quinones, (+)‐cyclospongiaquinone‐1 and (–)‐dehydrocyclospongiaquinone‐1, were efficiently synthesized in 10 and 12 steps and overall yields of 33 and 24 %, respectively, from commercially available (+)‐sclareolide. The synthetic strategy involves the following crucial steps: (i) assembly of the carbon skeleton by coupling the decalin segment to the aromatic moiety; (ii) one‐step construction of the dihydropyran ring by acid‐induced acetonide deprotection/ether cyclization of an olefinic decalin intermediate that contains the aromatic moiety; (iii) formation of the p ‐benzoquinone moiety by oxidation of a p ‐methoxyphenolic derivative to produce (+)‐cyclospongiaquinone‐1; and (iv) oxidative dehydrogenation at the C‐12–C‐12a bond of a tetracyclic intermediate to obtain (–)‐dehydrocyclospongiaquinone‐1.",10.1002/ejoc.201601160,2016-11-29,0.652114212743887
Journal of Organic Chemistry,"Total Synthesis of Polycavernoside A, A Lethal Toxin of the Red Alga <i>Polycavernosa </i><i>t</i><i>sudai</i>","[structure: see text] Two approaches to the synthesis of the aglycon 120 of polycavernoside A (1) were developed, only one of which was completed. The successful ""second-generation"" route assembled the aglycon seco acids 102 and 106 via Nozaki-Hiyama-Kishi coupling of aldehyde 70, prepared from methyl (S)-3-hydroxy-2-methylpropionate (72) and (S)-pantolactone (73), with vinyl bromide 71. The latter was obtained from a sequence which commenced from the silyl ether 24 of 3-hydroxypropionaldehyde and entailed cyclization of (Z)-zeta-hydroxy-alpha,beta-unsaturated ester 82. Regioselective Yamaguchi lactonization of trihydroxycarboxylic acids 102 and 106 and subsequent functional-group adjustments led to macrolactone 120, to which the fucopyranosylxylopyranoside moiety was attached. Stille coupling of the glycosidated aglycon 128 with dienylstannane 129 furnished polycavernoside A in a synthesis for which the longest linear sequence was 25 steps. The overall yield to lactone 120 was 4.7%.",10.1021/jo0503862,2005-06-14,0.6520862526101173
Organic Process Research & Development,Safe and Efficient Decarboxylation Process: A Practical Synthetic Route to 4-Chlorobenzo[<i>b</i>]thiophene,"We established an improved synthetic route to 4-chlorobenzo[ b ]thiophene, a key intermediate in brexpiprazole synthesis, via a practical decarboxylation process in three steps. Thermal analysis demonstrated that the coexistence of the decarboxylated product with DBU should be avoided and that removal of the product outside the reactor was vital. Our process yields the target compound by distillation under reduced pressure and is safe, highly batch efficient, cost-effective, and high yielding. Furthermore, manufacturing on a pilot scale was also accomplished through our approach.",10.1021/acs.oprd.5b00340,2015-12-14,0.6520660232194428
Synthesis,"An Improved Synthesis of (3<i>R</i>)-2-(<i>tert</i>-Butoxycarbonyl)-7-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic Acid","An improved synthesis of (3R)-2-(tert-butoxycarbonyl)-7-hydroxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid is described wherein a modified Pictet-Spengler reaction was employed to provide 95% yield of the product with 7% racemization or less. The enantiomeric excess of the final product was improved to 99.4% via recrystallization. The overall yield of this four-step synthesis provides the title compound in 43% starting from d-tyrosine.",10.1055/s-2008-1032211,2008-03-01,0.6520596197464547
Tetrahedron,"The First Total Synthesis of (±)-Terpestacin, HIV Syncytium Formation Inhibitor",,10.1016/s0040-4039(97)10494-4,1998-01-01,0.6520378347374823
Journal of Organic Chemistry,Concise and Efficient Synthesis of Calothrixin B,"A convergent synthesis of the naturally occurring alkaloid Calothrixin B is presented, which used a regioselective hetero-Diels-Alder reaction between a ""push-pull"" 2-aza-diene and a N-protected 3-bromo-9H-carbazole-1,4-dione to construct the five-ring skeleton of the molecule. Protection of the indole motif with a benzyl group was unattractive for delivery of sufficient target material because the removal of the protecting group had not been high yielding. We therefore elected to temporarily protect the indole motif with a more labile benzyloxycarbonyl group. Accordingly, the synthesis of calothrixin B proceeded in 17% overall yield over 9 steps from the commercially available 1,2,3,9-tetrahydro-4H-carbazol-4-one.",10.1021/jo061270o,2006-09-28,0.6520365723536763
Angewandte Chemie International Edition,An Efficient Formal Synthesis of the Human Telomerase Inhibitor (±)‐γ‐Rubromycin,"Balancing act: The correct balance of electronic factors in the naphthazarin and isocoumarin fragments facilitates the acid-mediated spiroketalization step to afford the key densely functionalized spiroketal (see picture; EOM=ethoxymethyl) in the formal synthesis of (±)-γ-rubromycin. A novel regioselective allyloxylation/Claisen rearrangement of 2-azido-1,4-naphthoquinone provides access to the highly oxygenated naphthazarin fragment.",10.1002/anie.200903316,2009-07-30,0.6520358334372653
Tetrahedron,"A diastereoselective synthesis of (S,S)-α-fluoro-2,2-dimethyl-1,3-dioxolane-4-propanoic acid methyl ester, a key intermediate for the preparation of anti-HIV effective fluorodideoxynucleosides",,10.1016/s0040-4039(00)76880-8,1994-05-01,0.6520020605542893
Organic Letters,Total Synthesis of (<i>S</i>)-Equol,"The first enantioselective total synthesis of (S)-equol is reported. The described route relies on an Evans alkylation to form the stereocenter and an intramolecular Buchwald etherification to generate the chroman ring. Key features of this method include its brevity, its scalability, and the low cost of starting materials. [reaction: see text].",10.1021/ol0620444,2006-11-01,0.6520002538500471
Organic Letters,Total Synthesis of (−)-(α)-Kainic Acid via a Diastereoselective Methylenecyclopropane Ring Expansion,[reaction: see text] A concise and enantioselective synthesis of (-)-(alpha)-kainic acid in 13 steps with an overall yield of 15% is reported. The pyrrolidine kainoid precursor with the required C2/C3 trans stereochemistry was prepared with excellent diastereoselectivity (>20:1) via a MgI(2)-mediated ring expansion of a tertiary methylenecyclopropyl amide. A selective hydroboration was then employed to set the remaining stereochemistry at the C4 position en route to (-)-(alpha)-kainic acid.,10.1021/ol051003p,2005-06-10,0.651973215097547
Chemical Science,Toward a more step-economical and scalable synthesis of spongistatin 1 to facilitate cancer drug development efforts,"An efficient, step-economical, and scalable synthesis of a diene-bearing AB spiroketal fragment of spongistatin 1, and a demonstration of its efficient coupling to an aldehyde derived from silylformylation of a homopropargyl alcohol to produce the entire complex C(13)-C(17) linker region are described. The scalability of the synthesis of the AB spiroketal fragment was demonstrated by the preparation of 34.5 grams by one chemist in ~60 workdays, and more than 40 grams overall. With this material in hand and having established a method for its efficient coupling to the CD fragment, we have set the stage for the rapid synthesis and evaluation of a series of analogs of the CD spiroketal.",10.1039/c3sc22186e,2013-01-01,0.6519674614339512
Journal of the American Chemical Society,"A Short, Highly Efficient Synthesis of Coenzyme Q<sub>10</sub>",The most efficient synthesis reported to date of ubiquinone (CoQ10) is described. A sequence consisting of six operations is involved which leads to crystalline material in an overall yield of >64%.,10.1021/ja021015v,2002-11-09,0.6519416428809157
Synthesis,Preparation of 3-Lithiofuran. An Efficient Synthesis of 3-Furoic Acid,,10.1055/s-1974-23343,1974-01-01,0.6519121596987423
Organic Letters,Gram-Scale Total Synthesis of (±)-Ibogamine,We describe the gram-scale total synthesis of (±)-ibogamine in nine steps and 24% overall yield. The approach features a Mitsunobu fragment coupling and macrocyclic Friedel-Crafts alkylation to establish the nitrogen-containing core of ibogamine. A regio- and diastereoselective hydroboration allows for simultaneous formation of the tetrahydroazepine and isoquinuclidine ring systems via sulfonamide deprotection and concomitant intramolecular cyclization.,10.1021/acs.orglett.3c01595,2023-06-13,0.6519082053426842
Journal of the American Chemical Society,Total Synthesis of (+)-Sieboldine A,"The first total synthesis of (+)-sieboldine A was completed in 20 steps from readily available (3aS,6aR)-3,3a,4,6a-tetrahydro-2H-cyclopenta[b]furan-2-one (5). Key steps are as follows: (a) a pinacol-terminated 1,6-enyne cyclization reaction to form the cis-hydrindanone core (11 --> 12), (b) formation of the spiro tetrahydrofuran ring by stereoselective DMDO oxidation of tricyclic dihydropyran intermediate 15, and (c) formation of the unprecedented N-hydroxyazacyclononane ring by cyclization of a thioglycoside precursor (18 --> 19).",10.1021/ja103666n,2010-05-19,0.6518796220734238
Synthesis,Enantioselective Synthesis of an Analogue of Nanaomycin A,"The enantioselective synthesis of (1R,3R)-deoxynanaomycin A (4) is reported. The key step involves introduction of the Stereocenter in (S)-homoallylic alcohol 10a using an asymmetric allylation of aldehyde 9. Lithium-halogen exchange of bromo acetate 11 triggered rapid intramolecular cyclization furnishing lactol 12 that underwent silane-mediated reduction providing (1R,3S)-naphthopyran 13. Dihydroxylation and oxidative cleavage gave aldehyde 15 that underwent two successive oxidations delivering (1R,3R)-deoxynanaomycin A (4) in high enantiopurity and an overall 7% yield over 12 steps from 1-naphthol (5). © Georg Thieme Verlag Stuttgart.",10.1055/s-2007-983848,2007-09-01,0.6518785344110056
Tetrahedron,Asymmetric synthesis of the northern segment of ephedradine C. A novel dihydrobenzo[b]furan formation,,10.1016/s0040-4039(99)01835-3,1999-12-01,0.6518694717226726
Organic Letters,IMDA/Retro-Mannich Approach to <i>cis</i>-Perhydroquinoline <i>Lycopodium</i> Alkaloids:  Asymmetric Synthesis of (+)-Luciduline,"[formula: see text] The first chiral auxiliary mediated asymmetric synthesis of the naturally occurring Lycopodium alkaloid (+)-luciduline has been accomplished. Key steps include an IMDA reaction of a chiral dihydropyridine, a subsequent retro-Mannich ring opening, and a novel cationic reductive cyclization reaction.",10.1021/ol990028j,1999-06-11,0.6518505976344727
Organic Process Research & Development,Amino Diol Based Asymmetric Syntheses of a Fused Benzazepine as a Selective D1 Dopamine Receptor,"A six-step practical synthesis of (6a S,13b R )-11-chloro-6,6a,7,8,9,13b-hexahydro-7-methyl-5 H -benzo[ d ]naphtho[2,1- b ]azepin-12-ol, a selective D1 dopamine receptor, is developed starting from (1 S,2 S )-phenyl-2-amino-1,3-propanediol. An acid-promoted stereo- and regioselective cyclization of the benzazepine ring was established. Three double reactions in which two functional groups are transformed in a single step were developed. These include the double hydrolysis, the double reduction, and the cyclization and demethylation. The use of practical and economical reagents reduced the cost significantly.",10.1021/op970105v,1997-09-01,0.651843765760289
Angewandte Chemie International Edition,Total Synthesis of (−)‐Decarbamoyloxysaxitoxin,"A facile and general synthetic strategy for saxitoxin derivatives has been developed, as exemplified by the efficient synthesis of (−)-decarbamoyloxysaxitoxin ((−)-doSTX), the putative enantiomer of the natural product, in 17 steps and in 10 % overall yield. The synthesis features a diastereoselective 1,3-dipolar cycloaddition and a direct oxidation with o-iodoxybenzoic acid (IBX; see scheme, Cbz=benzyloxycarbonyl).",10.1002/anie.200703326,2007-10-10,0.6518418442084069
Journal of Organic Chemistry,Synthesis of a NO-Releasing Prodrug of Rofecoxib,"[reaction: see text] A newly developed synthesis of a NO-releasing prodrug of rofecoxib is described. The highly productive process consists of five chemical steps and produces prodrug 1 in an overall 64% yield from commercially available 3-phenyl-2-propyn-1-ol (4). The synthesis is highlighted by the carbometalation reaction of propargyl alcohol 4 to generate the tetrasubstituted olefin core, sulfone acid 2. Additionally, two alternate end-game strategies to prepare NO-COXIB 1 from this intermediate were explored and developed: (1) a convergent synthesis where a bromonitrate side chain is introduced in one step and (2) a two-step sequence that first installs the requisite six-carbon ester side chain followed by chemoselective nitration.",10.1021/jo051712g,2005-12-17,0.6518201513206818
Journal of the American Chemical Society,Stereocontrolled Synthesis of (−)-Bactobolin A,"A stereoselective synthesis of the ribosome-binding antitumor antibiotic (-)-bactobolin A is reported. The presented approach makes effective use of (-)-quinic acid as a chiral pool starting material and substrate stereocontrol to establish the five contiguous stereocenters of (-)-bactobolin A. The key steps of the synthesis include a stereoselective vinylogous aldol reaction to introduce the unusual dichloromethyl substituent, a completely diastereoselective rhodium(II)-catalyzed C-H amination reaction to set the configuration of the axial amine, and an intramolecular alkoxycarbonylation to build the bicyclic lactone framework. The developed synthetic route was used to prepare 90 mg of (-)-bactobolin A trifluoroacetate in 10% overall yield.",10.1021/jacs.0c01554,2020-04-14,0.6518093179432882
Tetrahedron,"Total synthesis of deacetyl-caloporoside, a novel inhibitor of the GABAA receptor ion channel",,10.1016/0040-4039(96)00316-4,1996-04-01,0.6517815741201561
European Journal of Organic Chemistry,Addition of Indole to Methyl 2‐Chloro‐2‐cyclopropylideneacetate en Route to Spirocyclopropanated Analogues of Demethoxyfumitremorgine C and Tadalafil,"Abstract Indole readily added across the double bond of the highly reactive Michael acceptor methyl 2‐chloro‐2‐cyclopropylideneacetate ( 4 ) to yield 2‐chloro‐2‐(3′‐indolylcyclopropyl)acetate 5 (85%) which was converted in two steps into the racemic tryptophan analogue 7 in 90% yield. This in turn was transformed by a condensation and Pictet−Spengler sequence into the spirocyclopropane analogues, 11 , 13 and 15 , of both the natural product (demethoxy)fumitremorgine C ( 3b , 3 steps, 11% yield) and the potent PDE‐5 inhibitor Tadalafil ( 2 , 3 steps, 71% yield) as well as the original lead structure with a hydantoin backbone ( 1 , 2 steps, 79% yield). (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2005)",10.1002/ejoc.200400617,2005-02-01,0.6517623101466932
Organic Process Research & Development,"Practical and Scalable Process for the Preparation of 4-Amino-1,3-dimethylpyrazole Hydrochloride","A practical and scalable process for the preparation of 4-amino-1,3-dimethylpyrazole hydrochloride 1 is described. Compound 1 is a useful starting material; its preparation is achieved via a three-step sequence from methyl hydrazine and technical grade acetaldehyde dimethylacetal. The target molecule is isolated in high chemical and isomeric purity (>99.0% with respect to 4-amino-1,5-dimethylpyrazole).",10.1021/op900296p,2009-12-28,0.6517460899123195
European Journal of Organic Chemistry,Total Synthesis of (<i>E/Z</i>) <i>des</i>‐Hydroxy Triticone A and B,"Abstract The first total synthesis of des ‐hydroxy triticone A and B was achieved in 12 steps. The highly chemoselective, base mediated iodolactamization of olefins with N‐OMe amide motif is a key highlight of the synthesis.",10.1002/ejoc.202201205,2022-12-24,0.6517334821207493
Organic Letters,"Asymmetric Total Synthesis of 5,10-seco-Neoansamycin A","The first asymmetric total synthesis of 5,10-seco-neoansamycin A, a 19-membered cyclic octaketide, was achieved in 20 steps (with several steps being telescoped) and 6.7% overall yield starting from the reported compound, thus leading to the assignment of its absolute configuration. This convergent synthetic approach features late-stage macrolactamization, a judicious application of an asymmetric aldol reaction. This work will facilitate the synthesis of other ansamycin natural products and the explorations of 5,10-seco-neoansamycin A as a potential anticancer lead.",10.1021/acs.orglett.5c02111,2025-09-08,0.6517322381430661
Synthesis,"Total Synthesis of (±)-1,3,4,5-Tetragalloylapiitol","Starting from citraconic anhydride, the first total synthesis of (±)-1,3,4,5-tetragalloylapiitol has been demonstrated via a stepwise route involving generation of an apiitol derivative followed by benzoylation.",10.1055/s-0028-1083310,2009-01-09,0.6517216166946094
Organic Letters,A Concise Synthesis of Physostigmine from Skatole and Activated Aziridine via Alkylative Cyclization,"A concise synthetic route to physostigmine has been developed, where the key step relies on the alkylative cyclization of 1,3-dimethylindole with (Z)-aziridine catalyzed by Sc(OTf)3 and TMSCI in dichloromethane at -30 degrees C, to give 8 in 90% yield, which, in turn, can be readily converted into physostigmine.",10.1021/ol005603u,2000-03-11,0.6517081813821451
Organic Process Research & Development,A Practical Synthesis of the Pseudotripeptide RC-1291,"The rapid process development of a scaleable synthesis of the pseudotripeptide RC-1291 for preclinical and clinical evaluation is described. By employing a nontraditional N -to- C coupling strategy, the peptide chain of RC-1291 was assembled in high yield, with minimal racemization and in an economical manner by introducing the most expensive component last. A one-pot deprotection/crystallization procedure was developed for the isolation of RC-1291 free base, which afforded the target compound in excellent yield and with a purity of >99.5% without chromatographic purification.",10.1021/op0502506,2006-02-25,0.651660868105964
Synthesis,An Efficient Stereoselective Synthesis of Sphingosine,"All articles of this category A stereocontrolled synthesis of d-(+)- erythro -sphingosine ( 1 ), starting from d-xylose as chiral pool material and employing the addition-fragmentation reaction of tosyl hydrazone of 2,3 : 4,5-di -O -isopropylidene-d-xylose as key step for the chain extension with concomitant trans -selective C=C bond formation, is described. glycosphingolipids - sphingosine - d-xylose - stereoselective synthesis - addition-fragmentation",10.1055/s-1998-4482,1998-01-01,0.6516539204625207
Synthesis,A Stereoselective Synthesis of the Macrolide Core of Migrastatin,"A concise and efficient synthesis of the macrolide core of migrastatin, an antimetastatic agent, is reported. In this synthetic protocol, the key intermediate (4R,5S,6S)-6-methoxy-5-(4-meth­oxy­benzyloxy)-2,4-dimethylocta-2,7-dien-1-ol is obtained after dia­stereoselective aldol condensation, Lewis acid mediated diastereoselective addition, and an exclusive Z-olefination sequence have been employed. Yamaguchi esterification of the key intermediate, followed by ring-closing metathesis produced the desired macrolide in high selectivity and good yield.",10.1055/s-2008-1032028,2008-01-25,0.6516485009207643
Journal of Organic Chemistry,A Ring Contraction Strategy toward a Diastereoselective Total Synthesis of (+)-Bakkenolide A,"A diastereoselective route to (+)-bakkenolide A is presented from the readily available optically active Wieland-Miescher ketone. This novel synthesis of this sesquiterpene lactone features the following as key stereoselective transformations: (i) the ring contraction reaction of a octalone mediated by thallium(III) nitrate (TTN); (ii) a hydrogenation to create the cis-fused junction; and (iii) the formation of the C7 quaternary center through an enolate intermediate. Furthermore, during this work, the absolute configuration of a trinorsesquiterpene isolated from Senecio humillimus was assigned.",10.1021/jo100108b,2010-04-08,0.6516369074106053
Journal of Organic Chemistry,Synthesis of (+)-1-Epiaustraline,"A highly efficient total synthesis of (+)-1-epiaustraline ((+)-1), a tetrahydroxypyrrolizidine alkaloid of the alexine/australine subclass, is described. The key step is a tandem intramolecular [4 + 2]/intermolecular [3 + 2] nitroalkene cycloaddition involving dienylsilyloxy nitroalkene 3 and chiral vinyl ether 4, which establishes four of the five stereocenters present. The final center was installed by a diastereoselective dihydroxylation. Hydrogenolytic unmasking of the nitroso acetal tosylate 17 containing the silyl ether linkage was thwarted by a slow alkylation and an undesired Peterson-type elimination. Prior removal of the silicon moiety by Tamao-Fleming oxidation proceeded in excellent yield and provided a substrate suitable for hydrogenolysis and deprotection. The complete synthesis required only 10 steps to deliver the (+)-1-epiaustraline in 7.0% overall yield.",10.1021/jo0101510,2001-05-12,0.6516257433580132
Journal of Organic Chemistry,Total Synthesis of (+)-Crocacin C Using Hidden Symmetry,"A highly convergent and protecting-group-free synthesis of (+)-crocacin C, featuring an enzymatic enantioselective desymmetrization of a meso-diol, a base-induced ring opening of a THP ring, and a one-pot hydrostannylation/Stille coupling as the key steps, is reported. The natural product was obtained in 11 steps and 22.3% overall yield starting from readily available oxabicycle 1. Finally, a unique enantioselective step, an enzymatic desymmetrization, revealed four stereogenic centers and created one in C4 of the THP furnishing the dense building block 4 with high enantioselectivity (ee >98%).",10.1021/jo902582w,2010-02-03,0.65162086470558
European Journal of Organic Chemistry,"Synthesis of (–)-Cytoxazone, a Novel Cytokine Modulator Isolated fromStreptomyces sp.","Cytoxazone [(4R,5R)-(–)-5-hydroxymethyl-4-(4-methoxyphenyl)-2-oxazolidinone, 1], a new immunosuppressant, was synthesized by starting from p-methoxycinnamyl alcohol (2) employing the Sharpless asymmetric dihydroxylation as the key reaction in 26% overall yield (7 steps).",10.1002/(sici)1099-0690(199911)1999:11<2965::aid-ejoc2965>3.0.co;2-h,1999-11-01,0.6516023713896133
Tetrahedron,"A new, simple, one-pot route for the synthesis of azocine derivatives",,10.1016/j.tetlet.2014.10.055,2014-10-19,0.6516006377352559
Synlett,"A Practical Synthesis of [(1S,3S)-3-Aminocyclohexyl]methanol and 2-[(1S,3S)-3-Aminocyclohexyl]propan-2-ol, Useful Intermediates for the Preparation of Novel mPGES-1 Inhibitors","Microsomal prostaglandin E2 synthase-1 (mPGES-1) is a novel therapeutic target for the treatment of inflammation and pain. During the course of studies aimed at the identification of a suitable mPGES-1 inhibitor for clinical development, a need arose for preparing enantiomerically enriched amino alcohols (S,S)-2 and (S,S)-3. Described herein, a concise synthesis of (S,S)-2 and (S,S)-3 has been developed wherein both amino alcohols are derived from a commercially available, low-cost starting material.",10.1055/s-0031-1289884,2011-11-11,0.6515987641251306
Synlett,Total Synthesis of (+)-Cardiobutanolide through a Carbohydrate-Based Approach,"The naturally occurring styryllactone (+)-cardiobutanolide has been synthesized in a highly efficient manner using d-glucono-δ-lactone, as a chiral pool starting material. The synthesis involves the stereoselective addition of Grignard reagent to a chiral aldehyde, zinc-mediated reductive deoxygenation of 4-alkoxybut- 2-enoic acid moiety and asymmetric dihydroxylation as the key steps.",10.1055/s-0029-1218344,2009-11-03,0.6515845028003999
Synlett,An Improved Synthesis of the Aranorosin Nucleus,"All articles of this category An improved synthesis of the tetracyclic aranorosin nucleus ( 2 ) is described proceeding via an unusually stable ozonide (1,2,4-trioxolane), in the key step. The structure of ( 2 ) has been confirmed by X-ray crystallography.",10.1055/s-1992-21564,1992-01-01,0.6515761525738129
Organic Process Research & Development,"Large-Scale Enantioselective Reduction of 2,3-Disubstituted Indenopyridine Enables a Practical Manufacturing Process for an 11β-HSD-1 Inhibitor","An economical and practical manufacturing process for an 11β-HSD-1 inhibitor is reported. The key feature of the synthesis is the identification of a unique and effective MeO-BoQPhos ligand for the Ir-catalyzed asymmetric hydrogenation of a fused tricyclic indenopyridinium salt. It is the first highly reactive chiral P,N ligand system to be utilized in asymmetric pyridine reduction. The enantioenriched indanopiperidine was produced with a low catalyst loading of 1000 ppm [Ir(COD)Cl] 2 . The challenges and solutions for final active pharmaceutical ingredient (API) physicochemical properties are also described. This asymmetric synthesis of the API was accomplished in 38% overall yield with >99.8% ee and >99.5 area % purity. This overall process results in a much shorter production cycle and significant waste reduction on the manufacturing scale.",10.1021/acs.oprd.1c00290,2021-11-08,0.6515741593227178
Organic Letters,Synthetic Studies toward Lapidilectine-Type <i>Kopsia</i> Alkaloids,"A rapid synthesis of the tetracyclic core of Kopsia indole alkaloids related to lapidilectine B, grandilodine C, and tenuisine A is reported. Key to the success of this route was an efficient and scalable Ugi four-component coupling to install all the necessary carbons found in the natural products.",10.1021/ol203302f,2012-01-03,0.6515625645099267
Journal of Organic Chemistry,Synthetic Route to Chiral Indolines via Ring-Opening/C–N Cyclization of Activated 2-Haloarylaziridines,"A practical approach for the synthesis of 3-substituted indolines via regio- and stereoselective SN2-type ring-opening of 2-(2-halophenyl)-N-tosylaziridines with heteroatomic nucleophiles (O, N, and S) followed by palladium-catalyzed intramolecular C-N cyclization is reported in excellent yields (up to >99%) and enantiomeric excess (ee 99%).",10.1021/jo400287a,2013-04-02,0.6515594714031475
Synlett,Synthetic Access to the First Spirocyclopropyl Iminosugar,"The synthesis of the first spirocyclopropyl iminosugar has been achieved in six steps and 13% overall yield from commercially available 2,3,5-tri-O-benzyl-d-arabinose. The synthesis is based on an efficient two-step reaction involving the titanium-mediated aminocyclopropanation of 2,3,5-tri-O-benzyl-4-O-methanesulfonyl-d-arabinononitrile and the subsequent cyclization resulting from in situ nucleophilic attack of the so-formed amine. Addition of a Lewis acid during the cyclopropanation-cyclization sequence greatly improved the yields.",10.1055/s-2005-923582,2006-01-01,0.6515576722649055
Organic Process Research & Development,Copper-Catalyzed C–N Coupling in the Synthesis of Integrase Inhibitors of Immunodeficiency Viruses,"This contribution describes the total synthesis of a complex macrocyclic integrase inhibitor, a key enzyme involved in the infection process of various immunodeficiency viruses. The key transformation of the synthetic strategy was the selective C–N coupling of a sulfonamide to a heteroaryl bromide in the presence of potentially competing amide and carbamate functionalities. The transformation was accomplished with CuI catalysis using bypiridine as the ligand in the presence of base and enabled a convergent approach to the target molecule.",10.1021/op400228z,2013-10-15,0.6515114189880657
Journal of Organic Chemistry,"Collective Syntheses of Guaiane Sesquiterpenes: Stereoselective Syntheses of (+)-Dysodensiol F, (+)-10β,14-Dihydroxy-<i>allo</i>-aromadendrane, and (−)-Dendroside C Aglycon","A collective synthetic route for tricyclic guaiane sesquiterpenes and total syntheses of (+)-dysodensiol F, (+)-10β,14-dihydroxy- allo -aromadendrane, and (−)-dendroside C aglycon starting from a versatile hydroazulene intermediate were accomplished. The key features of these syntheses involve late-stage carbene-mediated diastereoselective cyclopropanation, construction of an unusual cis- fused-hydroazulene skeleton via intramolecular Dieckmann condensation, and highly stereoselective tandem conjugate addition/intramolecular allylic alkylation to afford a 5/7/3 tricyclic skeleton of guaiane natural products. The synthesis of (−)-dendroside C aglycon and the first total synthesis of (+)-dysodensiol F and (+)-10β,14-dihydroxy- allo -aromadendrane are described in detail. Activation of the Nrf2/ARE signaling pathway by (−)-dendroside C aglycon is also disclosed via our synthesis.",10.1021/acs.joc.0c01907,2020-10-13,0.6515037534770621
Journal of Organic Chemistry,Total Synthesis of (−)-Sessilifoliamide J,An efficient synthesis of the Stemona alkaloid (-)-sessilifoliamide J (1) in 12 steps and 7.7% overall yield from the known building block 8 is presented. The synthesis features the Corey lactonization reaction and a highly diastereoselective α-methylation reaction to build the spiro-lactone moiety.,10.1021/jo3014484,2012-09-04,0.6514992996458324
Journal of the American Chemical Society,"Enantioselective Divergent Syntheses of <i>Cephalotaxus</i> Alkaloids: (−)-Cephalotaxine, (−)-Cephalotine B, and (−)-Fortuneicyclidins A and B","A new strategy focusing on the last-stage asymmetric assembly of the ring D, which inherently possesses the densest part of stereogenic centers and functional groups in the A/B/C/D ring system of (-)-cephalotaxine, has been developed, in which a novel Rh-catalyzed asymmetric (2 + 3) annulation of tertiary enamides with enoldiazoacetates is designed and explored for enantioselective construction of the crucial cyclopentane ring D bearing a unique spirocyclic aza-quaternary stereocenter. Based on the expeditious access of chiral functionalized building block with the tetracyclic A/B/C/D ring system, a concise enantioselective total synthesis of (-)-cephalotaxine starting from readily available homopiperonyl alcohol has been achieved in nine steps with only two column chromatography purifications. Following the tactical introduction of the Meinwald rearrangement, enantioselective divergent syntheses of (-)-cephalotine B with an additional C3-O-C11 oxo-bridged bond (14 steps), (-)-fortuneicyclidin B with an unprecedented C3-C10 bond (14 steps), and its 2-epimer (-)-fortuneicyclidin A (16 steps) have been also accomplished for the first time.",10.1021/jacs.3c01572,2023-04-12,0.6514794349845161
Organic Letters,Concurrent Hydrogenation of Three Functional Groups Enables Synthesis of C3′-Homologated Nucleoside Amino Acids,"Internucleoside amide linkages are excellent mimics of phosphodiesters in RNA and may be used to optimize the properties of short interfering RNAs. Herein we report a remarkably straightforward, efficient and step economic synthesis of C3'-homologated uridine and adenosine amino acids starting from nucleosides in six steps (31% overall yield) and eight steps (16% overall yield), respectively. The key enabling step is a one-pot multifunctional group transformation including a stereoselective hydrogenation, termed ""Global Hydrogenation"".",10.1021/acs.orglett.7b01934,2017-07-21,0.6514278734935556
Journal of Organic Chemistry,An Alternative Synthesis of Dolby−Weinreb Enamine en Route to Cephalotaxine,"A novel alternative synthesis of the Dolby-Weinreb enamine (2) was achieved from readily available amino dione 6 by a mild transannular Clemmensen-Clemo-Prelog-Leonard reductive rearrangement, which thus constitutes a formal total synthesis of cephalotaxine.",10.1021/jo050143+,2005-04-16,0.651401006935883
Tetrahedron,A new synthesis of 1β-methylcarbapenems using NBS-promoted cyclization as a key step,,10.1016/s0040-4039(00)73421-6,1994-08-01,0.6513990019275863
Tetrahedron,Selective [2+1] aziridination of conjugated dienes with a nitridomanganese complex: a new route to alkenylaziridines,,10.1016/s0040-4039(00)01219-3,2000-09-01,0.6513966054487476
Tetrahedron,"Convergent synthesis of a key intermediate for hypocholesterolemic agent 1233A, starting from methyl 3-hydroxy-2-methylpropanoate and asymmetrized bis(hydroxymethyl)acetaldehyde (BHYMA*)",,10.1016/s0040-4039(00)73162-5,1994-06-01,0.6513867722426925
European Journal of Organic Chemistry,Stereoselective Synthesis of the DE Ring Portion of Kadcoccilactone A by a Radical Addition/Cyclization Approach,"Abstract A stereoselective synthesis of the DE ring portion of kadcoccilactone A, triterpenoid isolated from Kadsura coccinea , has been achieved starting from a chiral building block, utilizing a photocatalytic decarboxylative addition/cyclization/fragmentation sequence to construct the five‐membered ring and intramolecular alkylation to create the quaternary stereocenter as key steps.",10.1002/ejoc.202201201,2022-10-23,0.6513847754742151
Tetrahedron,A Novel Synthetic Approach Towards Phytosiderophores: Expeditious Synthesis of Nicotianamine and 2′-Deoxymugineic Acid,,10.1016/s0040-4039(97)10496-8,1998-01-01,0.6513813998712251
Synlett,A Novel Route Towards the Synthesis of Spirocyclic Bislactones<i />,"A novel route towards the synthesis of 1,7-dioxa­spiro[4.4]nonane-2,6-diones, based on the versatile reactivity of an acyclic trimethylenemethane dianion synthon, is presented.",10.1055/s-2008-1078489,2008-06-11,0.6513811021072121
Tetrahedron,Synthesis of macrocyclic terpenoids by intramolecular cyclization X. Total synthesis of methyl ceriferate-I,,10.1016/s0040-4039(00)84474-3,1986-01-01,0.6513764691351797
Journal of Organic Chemistry,Synthesis of Louisianin C,"The synthesis of louisianin C (3), a member of a small family of 3,4,5-trisubstituted pyridyl natural products, is achieved in six steps and 11% overall yield starting from commercially available 3,5-dibromopyridine. The key step is a fluoride-induced desilylation-cyclization to afford carbinol 12.",10.1021/jo0341618,2003-05-10,0.6513750636666553
Journal of Organic Chemistry,Enantioselective Formal Synthesis of Nectrisine Using a Palladium-Catalyzed Asymmetric Allylic Amination and Cross-Metathesis as Key Steps,"A formal enantioselective synthesis of nectrisine, a potent α-glucosidase inhibitor, was carried out starting from butadiene monoepoxide through a synthetic sequence involving enantioselective allylic substitution, cross-metathesis, dihydroxylation, and cyclization.",10.1021/acs.joc.6b00494,2016-05-16,0.6513674484122218
Journal of Organic Chemistry,Total Synthesis of (±) Carbocyclic Polyoxin C and Its α-Epimer,"Carbocyclic polyoxin C (2) and its alpha-epimer 3 were synthesized in racemic form in an efficient and diastereodivergent fashion from cis-4-(N-tert-butylcarbamoyl)cyclopent-2-en-1-ol (5a). This synthesis features a Pd(0)-catalyzed substitution reaction, a novel, mild reduction of an alpha-nitro ester to an amino acid ester, and an improved procedure for uracil ring formation.",10.1021/jo971711r,1998-01-22,0.6513504940671309
Synthesis,A New and Convenient Synthesis of 1-Aryl-2-dimethylaminoethanols,"An efficient two-step synthesis of 1-aryl-2-dimethylaminoethanols 4 is described, consisting of oxazolidine 3 generation from the cycloaddition of an azomethine ylide to an aldehyde, followed by reductive ring-opening.",10.1055/s-2001-16077,2002-07-26,0.6513492609686837
Journal of Organic Chemistry,Stereoselective Total Synthesis of (−)-Cleistenolide,"A facile stereoselective total synthesis of cleistenolide (1) from the natural chiral template d-arabinose has been achieved in eight steps and 49% overall yield, employing key steps including Wittig olefination, selective 1,3-trans-acetal formation, and modified Yamaguchi esterification.",10.1021/jo101059e,2010-07-22,0.6513370296872191
Organic Letters,Formal Synthesis of (±)-Aplykurodinone-1 through a Hetero-Pauson–Khand Cycloaddition Approach,"The tricyclic intermediate 2 has been synthesized in eight steps from known compound 6 in 20% overall yield. As such, this constitutes a highly efficient formal synthesis of (±)-aplykurodinone-1. This synthesis features a unique, one-pot, intramolecular hetero-Pauson-Khand reaction (h-PKR)/desilylation sequence to expeditiously construct the tricyclic framework, providing valuable insights for expanding the scope and boundaries of h-PKR.",10.1021/acs.orglett.7b00068,2017-02-20,0.651320363897846
Journal of the American Chemical Society,The Total Synthesis of (±)-Ginkgolide B,"The total synthesis of the potent PAF antagonist ginkgolide B has been accomplished. The complex architecture of ginkgolide B which includes six rings, eleven stereogenic centers, ten oxygenated carbons, and four contiguous fully substituted carbons is a daunting challenge for chemical synthesis. The synthesis of ginkgolide B was accomplished through a stereoselective intramolecular photocycloaddition of enone 5 to construct the congested core of the molecule. The photocycloaddition substrate was prepared through technology for the construction of carboalkoxycyclopentenones previously reported from these laboratories. Regioselective cyclobutane fragmentation and further functionalization of the photoadduct 4 provided the key pentacyclic intermediate. Acid-catalyzed rearrangement and epoxide opening were key transformations in the production of ginkgolide B from the pentacyclic intermediate.",10.1021/ja001747s,2000-08-18,0.651269406344733
Tetrahedron,Selective synthesis of imidazolidine-2-thiones via ring expansion of aziridine-2-carboxylates with isothiocyanates,,10.1016/j.tetlet.2016.07.040,2016-07-15,0.6512549717515222
Organic Process Research & Development,"Improved Synthesis of the Selected Serine Protease uPA Inhibitor UAMC-00050, a Lead Compound for the Treatment of Dry Eye Disease","The α-aminophosphonate UAMC-00050, a newly developed trypsin-like serine protease inhibitor, is a lead compound for the treatment of dry eye syndrome and ocular inflammation. The medicinal chemistry route developed at the University of Antwerp possessed several problems hampering the scale-up such as poor yields for some of the steps, hazardous reagents, and environmental footprint. Herein, we report an optimized route for the UAMC-00050, in which environmental unfriendly solvents were excluded, hazardous reagents were replaced with safer alternatives, and are more efficient in terms of atom economy. Every reaction step was optimized to reach a higher yield, and design of experiment was used to find the optimum conditions in the last step. Furthermore, all the flash chromatography purifications of intermediates were replaced with plug filtration, slurry purifications, or crystallization. The overall yield was increased from 3% in the medicinal chemistry route to 22% in the process development route.",10.1021/acs.oprd.2c00244,2022-09-30,0.6512485050368333
Synlett,Concise Total Synthesis of (+)-Aphanorphine,Abstract A concise total synthesis of (+)-aphanorphine is described. The key features of the strategy include a Pd-catalyzed intermolecular trimethylenemethane [3+2]-cycloaddition to form ring C and a Co-catalyzed radical cyclization through a hydrogen-atom transfer to close ring B. The synthesis was completed in six steps.,10.1055/s-0037-1610769,2021-04-08,0.6512202100349563
Organic Letters,Highly Convergent Route to Cyclopeptide Alkaloids. Total Synthesis of Ziziphine N,"[structure: see text]. A highly convergent protocol to cyclopeptide alkaloids, as demonstrated by the first total synthesis of antiplasmodial agent ziziphine N, is developed. The key elements include construction of its aryl ether unit via Mitsunobu reaction, installation of its enamide part via CuI/N,N-dimethylglycine-catalyzed coupling reaction, and ring closure with coupling agents such as FDDP and DPPA.",10.1021/ol070271f,2007-03-01,0.65120337910216
Synlett,Synthesis of an Advanced Intermediate of the Macrotricyclic Core of Roseophilin,"A facile approach for the preparation of a cyclopenta[b]pyrrole derivative, the key precursor in Frontier’s synthesis of the macrotricyclic core of roseophilin, was developed. The key steps involved two successive pyrrole acylations and a Sc(OTf)3-catalyzed Nazarov cyclization reaction.",10.1055/s-0031-1289882,2011-11-11,0.6511743915887067
Synlett,"Enantioselective Approach to Tropane Skeleton: Synthesis of (1<i>S</i>,5<i>S</i>,6<i>R)</i>-6-Hydroxy-8-methyl-8-azabicyclo[3.2.1]octan-3-one","The original and classical Mannich-type construct for the tropane skeleton, developed over half a century ago by Willstatter, Robinson and Schopf as the first biomimetic synthesis, has been employed for the enantioselective construction of 6-beta-hydroxytropinone. The component compounds of this novel one-step Mannich-type condensation sequence are acetonedicarboxylic acid, methylamine hydrochloride and (2R)-hydroxy-1,4-butanedial, in turn prepared from tert-butyl (R)-3-hydroxy-4-pentenoate as the starting chiral synthon",10.1055/s-2004-836037,2004-11-29,0.6511660973013831
European Journal of Organic Chemistry,"Concise Total Synthesis of Permethylated Anigopreissin A, a New Benzofuryl Resveratrol Dimer","Abstract The versatile preparation of permethylated anigopreissin A ( 1 ) has been accomplished from methyl 3,5‐dihydroxybenzoate. The key steps of the synthesis are sequential Sonogashira and Suzuki cross‐couplings for the construction of the 2,3‐diarylbenzo[ b ]furan moiety and Wittig olefination for the introduction of the styryl group.",10.1002/ejoc.201101422,2011-11-28,0.6511657336681405
Tetrahedron,"Synthesis of STM2457, a selective small-molecule inhibitor of METTL3",,10.1016/j.tetlet.2024.155077,2024-04-18,0.6511630435293774
Organic Letters,Asymmetric Divergent Total Syntheses of (+)-Decursivine and (+)- Serotobenine via Intramolecular Fischer Indole Synthesis,"A new asymmetric synthetic route to (+)-decursivine and (+)-serotobenine is formulated. The key developments are the de novo construction of the crucial eight-membered 3,4-fused tricyclic indole ring engaged by the intramolecular Fischer indole synthesis and the stereocontrolled assembly of the dihydrobenzofuran subunit mediated by the asymmetric intramolecular Rh-carbenoid C–H insertion. BF 3 -mediated selective C15 epimerization followed by removal of the amine masking groups completed the target natural compounds’ asymmetric and divergent total syntheses.",10.1021/acs.orglett.2c00848,2022-04-12,0.6511324540643876
Journal of Organic Chemistry,"Improved Synthesis of 2,2‘-Bipyrimidine","A high-yield synthesis was developed for the preparation of 2,2'-bipyrimidine (1) using the Ullmann coupling of 2-iodopyrimidine. The new procedure was also used for the preparation of 4,4',6,6'-tetramethyl-2,2'-bipyrimidine (2) and 5,5'-dibromo-2,2'-bipyrimidine (3).",10.1021/jo0255781,2002-08-03,0.6511120557161679
European Journal of Organic Chemistry,Convergent Synthesis of 1α-Hydroxyvitamin D5,"An eleven-step, high-yielding (46%) synthesis of 1α-hydroxyvitamin D5 (2) starting from vitamin D2 (4) is described, in which a Julia olefination sequence is used for the construction of the (24R)-ethyl-substituted side chain.",10.1002/1099-0690(200008)2000:15<2755::aid-ejoc2755>3.0.co;2-g,2000-08-01,0.6511081437298694
Organic Letters,Alkynyltrifluoroborates as Versatile Tools in Organic Synthesis:  A New Route to Spiroketals,[reaction: see text] A simple and efficient two-step approach to spiroketals is described. Key steps include the preparation of functionalized hydroxyl alpha-alkynones by ring-opening reactions of lactones with lithium alkynyltrifluoroborates followed by a palladium-catalyzed hydrogenation/spirocyclization of the prespiroketal intermediate.,10.1021/ol047987k,2004-11-25,0.6511074543694405
Journal of Organic Chemistry,Stereocontrolled Total Synthesis of (−)-Englerin A,"The total synthesis of (-)-englerin A, a potent and selective inhibitor of renal cancer cell lines, is described. The key feature includes the stereocontrolled construction of the cyclopentane structure by taking advantage of a base-promoted epoxynitrile cyclization.",10.1021/jo301145r,2012-08-08,0.6510923006815122
Journal of Organic Chemistry,An Expeditious Enantioselective Synthesis of Antimycin A<sub>3b</sub>,"A straightforward enantioselective route to (+)-antimycin A3b is presented, which used a TiCl4-mediated asymmetric aldolization to construct C-7/C-8 and BnOH/DMAP to remove the chiral auxiliary with concurrent protection of the carboxylic group, respectively. Closing the dilactone ring was achieved in 62% yield (previously 0.8%, 13.4%, or 20%) in the presence of the C-8 ester functionality. The overall yield (34.5%) was significantly higher than that (0.019-3.6%) of the earlier routes.",10.1021/jo0604890,2006-05-01,0.651082837135393
Tetrahedron,Organophosphorus enamines I. A new synthetic route to β-keto diphenylphosphine oxides,,10.1016/s0040-4039(01)96719-x,1971-01-01,0.6510746843370245
Organic Letters,"Stereoselective, Oxidative C−C Bond Coupling of Naphthopyran Induced by DDQ:  Stereocontrolled Total Synthesis of Deoxyfrenolicin","A formal total synthesis of pyranonaphthoquinone natural product deoxyfrenolicin 1 is described. The key step in the synthesis involves the use of stereoselective 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ)-induced C−C bond coupling of the naphthopyran 10 with allyltriphenyltin to give exclusively 1,3- trans naphthopyran derivative 23 . The naphthopyran 10 was obtained via oxa-Pictet−Spengler cyclization of substituted naphthalene 22, which was derived by regioselective benzannulation of chromium carbene complex 12 with acetylene 18 . This newly developed synthetic route employing a tandem benzannulation/oxa-Pictet−Spengler cyclization/DDQ-induced coupling strategy should also be applicable to the synthesis of other pyranonaphthoquinone natural products such as kalafungin 4 and nanaomycin 5 .",10.1021/ol9909738,1999-10-09,0.6510682997835919
Organic Letters,Biomimetic Synthesis of the Shimalactones,"A biomimetic synthesis of shimalactone A and B is described. Its key features are an unprecedented acid-catalyzed cyclization of a dienyl beta-ketolactone and a Stille coupling/8pi-6pi electrocyclization cascade to create the oxabicyclo[2.2.1]heptane and bicyclo[4.2.0]octadiene, respectively. The synthesis is convergent and void of protecting groups.",10.1021/ol702806v,2007-12-12,0.6510619155437657
Journal of Organic Chemistry,Total Synthesis of (+)-Angelmarin,"An efficient 8-step enantioselective total synthesis of (+)-angelmarin, starting from commercially available umbelliferone, has been achieved. Key reactions include olefin cross-metathesis and a Shi epoxidation-cyclization sequence.",10.1021/jo900613u,2009-05-21,0.6510541458106466
Organic Letters,Scalable Total Synthesis of Leucascandrolide A Macrolactone Using a Chiral Phosphoric Acid/CuX Combined Catalytic System,A scalable total synthesis of leucascandrolide A macrolactone has been accomplished with a longest linear sequence of 17 steps from readily available feedstocks in 31.2% yield. The key steps in this synthesis are the enantioselective allylation reaction by chiral phosphoric acid (CPA)/CuBr cooperative catalysis and the diastereoselective catalytic crotylation in the presence of CPA with CuCl. These catalytic reactions can be performed on a gram scale to afford the desired products with excellent stereoselectivities.,10.1021/acs.orglett.3c00450,2023-03-15,0.6510375133726038
European Journal of Organic Chemistry,"Unified Synthesis of the Marine Sesquiterpene Quinones (+)‐Smenoqualone, (–)‐Ilimaquinone, (+)‐Smenospongine, and (+)‐Isospongiaquinone","The marine sesquiterpene quinones (+)‐smenoqualone, (–)‐ilimaquinone, (+)‐smenospongine, and (+)‐isospongiaquinone were efficiently synthesized in a unified manner starting from a known trans ‐decalin derivative, which is accessible from (+)‐5‐methyl Wieland–Miescher ketone. The synthetic method involved the following key steps: (i) assembly of the whole carbon skeleton by coupling the decalin segment to an aromatic moiety; (ii) p ‐quinone formation by strategic salcomine oxidation of phenolic intermediates; (iii) direct conversion of (–)‐ilimaquinone into (+)‐isospongiaquinone by p TsOH‐induced isomerization of the C‐4 olefinic double bond; (iv) site‐selective amination of a dimethoxy‐ p ‐quinone intermediate by substitution of the C‐18 methoxy group with an amino group; and (v) one‐step construction of the requisite tetracyclic core structure by sequential BF 3 · Et 2 O‐induced rearrangement/cyclization of an olefinic decalin intermediate having an aromatic moiety. The syntheses of (+)‐smenoqualone and (+)‐smenospongine are reported here for the first time.",10.1002/ejoc.201700609,2017-05-25,0.6510324361736085
Journal of Organic Chemistry,Toward the Total Synthesis of FR901483:  Concise Synthesis of the Azatricyclic Skeleton,"A concise synthesis of the azatricyclic core of FR901483 has been accomplished using a novel strategy that involves a nucleophilic addition to an N-acyl iminium ion, a ring-closing metathesis, a diastereoselective hydroboration, and a lactone-lactam rearrangement that worked well in a preliminary model study. Extension of this approach to the synthesis of a more highly functionalized intermediate that could be transformed into (-)-FR901483 first required the development of a new protecting group, the 1-ethylallyloxycarbamate group, for amines that may be removed under mild conditions. However, because the stereoselectivity in a key step in which a functionalized allyl zinc reagent was added to an intermediate hydroxy-substituted imine was low, this route to (-)-FR901483 is no longer being pursued.",10.1021/jo070732a,2007-06-08,0.6510276494322107
Journal of the American Chemical Society,A Bioinspired Cyclization Sequence Enables the Asymmetric Total Synthesis of Dictyoxetane,"We have developed the first synthesis of the unique oxetane containing diterpene (+)-dictyoxetane. Our retrosynthetic planning was guided by the putative biosynthesis of the unprecedented 2,7-dioxatricyclo[4.2.1.0(3,8)]nonane ring system. A bioinspired 4-exo-tet, 5-exo-trig cyclization sequence enabled the construction of the synthetically challenging dioxatricyclic framework. The overall synthesis proceeds in 15 linear steps from a known and readily available trans-hydrindane fragment. In addition, we were able to realize the first dyotropic rearrangement of an epoxide-oxetane substrate.",10.1021/jacs.6b03720,2016-05-09,0.6510217283217534
Journal of the American Chemical Society,Enantioselective Total Synthesis of FD-891,The enantioselective synthesis of FD-891 has been achieved with a longest linear sequence of 21 steps. The synthetic strategy involves the use of aldol additions of a chlorotitanium enolate of N-acylthiazolidinethiones as the key reaction to establish 6 of the 10 stereogenic centers. A key cross-metathesis and a late-stage Julia olefination serve to assemble three key subunits.,10.1021/ja060018v,2006-02-14,0.6510020801531936
Journal of Organic Chemistry,"One-Pot Synthesis of Dibenzo[<i>b</i>,<i>f</i>]oxepines and Total Synthesis of Bauhinoxepin C","In this work, we report a novel and simple one-pot synthesis of substituted dibenzo[ b, f ]oxepines under transition-metal-free conditions. This cascade process involves nucleophilic aromatic substitution followed by Knoevanagel condensation, as evidenced by the isolated reaction intermediates. We have also achieved the synthesis of anticancer bauhinoxepin C in 7 steps with 5.1% overall yield using this synthetic approach.",10.1021/acs.joc.0c02452,2021-01-05,0.6509922755580518
Journal of Organic Chemistry,"Asymmetric Syntheses of the Homalium Alkaloids (−)-(<i>S</i>,<i>S</i>)-Homaline and (−)-(<i>R</i>,<i>R</i>)-Hopromine","The highly diastereoselective conjugate additions of the novel lithium amide reagents lithium (R)-N-(3-chloropropyl)-N-(α-methylbenzyl)amide and lithium (R)-N-(3-chloropropyl)-N-(α-methyl-p-methoxybenzyl)amide to α,β-unsaturated esters were used as the key steps in syntheses of the homalium alkaloids (-)-(S,S)-homaline and (-)-(R,R)-hopromine. The asymmetric synthesis of (-)-(S,S)-homaline was achieved in 8 steps and 18% overall yield, and the asymmetric synthesis of (-)-(R,R)-hopromine was achieved in 9 steps and 23% overall yield, from commercially available starting materials in each case. These syntheses therefore represent by far the most efficient total asymmetric syntheses of these alkaloids reported to date. A sample of the (4'R,4''S)-epimer of hopromine was also produced using this approach, which provided the first unambiguous confirmation of its absolute configuration and therefore that of natural (-)-(R,R)-hopromine.",10.1021/jo3012732,2012-07-24,0.6509508966105766
Organic Letters,Stereoselective Synthesis of the Epicoccin Core,"A short, convergent, and asymmetric synthesis of the epicoccin core was achieved using a phosphite-promoted one-step condensation of a complex proline-type amino acid. Key features of the assembly of this amino acid were a double-bond isomerization/vinylation/ring-closing metathesis strategy as well as an efficient, highly diastereoselective [2 + 2] cycloaddition of a ketene to an enecarbamate, derived from L-pyroglutamic acid.",10.1021/ol901919c,2009-09-18,0.6509424098042318
Journal of the American Chemical Society,An Enantioselective Total Synthesis of (+)- and (−)-Saudin. Determination of the Absolute Configuration,"A short efficient enantioselective synthesis of both (+)- and (-)-saudin, a naturally occurring hypoglycemic diterpene, is described. This synthesis establishes the absolute configuration of natural (-)-saudin for the first time. The key steps include the enantioselective construction of a dimethyl Hagemann's ester by an asymmetric Michael reaction and establishment of the key 1,3 disposed quaternary centers by means of a novel Ti(IV) promoted Claisen rearrangement. The assembly of the polycyclic ketal skeleton was likely under kinetic control proceeding via formation of the C1oxygen-C7 bond through an oxonium ion intermediate in the final stage.",10.1021/ja017194i,2001-12-14,0.6509313150035322
Synlett,Asymmetric Synthesis of Carbapenems Using Chiral Acetals: Synthesis of a Key Intermediate to (+)-PS-5,"(opens in new window) Buy Article (opens in new window) Permissions and Reprints (opens in new window) All articles of this category (opens in new window) Coupling reaction of the chiral imine acetal 5 [(4 S ,5 S )-4,5-bis (methoxymethyl)-2- [(4-methoxyphenylimino)methyl]-2-(3-methoxyphenyl)-1, 3-dioxolane] and lithium enolate of methyl acetate proceeded in a highly diastereoselective manner to give ß-lactam 6 . The reaction was applied to the synthesis of a key intermediate 11 [(2 S ,3 R )-3-ethyl-4-oxo-2-azetidineacetic acid] to (+)-PS-5.",10.1055/s-1992-21256,1992-01-01,0.6508971266899076
Chemical Science,"Catalytic, enantioselective synthesis of stilbene cis-diamines: A concise preparation of (−)-Nutlin-3, a potent p53/MDM2 inhibitor","The first highly diastereo- and enantioselective additions of aryl nitromethane pronucleophiles to aryl aldimines are described. Identification of an electron rich chiral Bis(Amidine) catalyst for this aza-Henry variant was key to this development, leading ultimately to differentially protected cis-stilbene diamines in two steps. This method then became the lynchpin for an enantioselective synthesis of (-)-Nutlin-3 (Hoffmann-LaRoche), a potent cis-imidazoline small molecule inhibitor of p53-MDM2 used extensively as a probe of cell biology and currently in drug development.",10.1039/c1sc00061f,2011-01-01,0.6508833480479937
European Journal of Organic Chemistry,"Total Synthesis and Olfactory Evaluation of (1<i>R</i>*,3<i>S</i>*,6<i>S</i>*,7<i>S</i>*,8<i>S</i>*)‐ 3‐Hydroxy‐6,8‐dimethyltricyclo[5.3.1.0<sup>3,8</sup>]undecan‐2‐one: A New Synthetic Route to the Patchoulol Skeleton","Abstract The superposition analysis of (–)‐patchoulol ( 1 ), the odorous principle of patchouli oil, with the recently discoveredhigh‐impact spirocyclic patchouli odorant (+)‐(1 S ,4 R ,5 R ,9 S )‐1‐hydroxy‐1,4,7,7,9‐pentamethylspiro[4.5]decan‐2‐one ( 2 ) resulted in the question as to whether a patchoulolderivative in which the gem ‐dimethyl group is replacedby a carbonyl function would be a powerful patchouliodorant. The total synthesis of the racemic superstructure (1 R *,3 S *,6 S *,7 S *,8 S *)‐3‐hydroxy‐6,8‐dimethyltricyclo[5.3.1.0 3,8 ]undecan‐2‐one ( 3 ) was accomplished in 13 steps from the inexpensive commercial odorant Cyclal C ( 7 ) with a total yield of 7 %. Conversion of 7 to the corresponding enamine 8 and subsequent copper‐catalyzed oxidative degradation afforded 2,4‐dimethylcyclohex‐3‐enone ( 6 ), which was subjected to a Robinson annulation with 1,4‐dimethoxybutan‐2‐one ( 9 ). The carbonyl function of the resulting annulation product 10 was removed by LAH reduction, acylation with Ac 2 O, and dissolving metal reduction. The deoxygenated methyl enol ether 12 thus obtained was then cleaved by mild hydrolysis with oxalic acid, and the resulting 2,9‐dimethyl‐Δ 1 ‐octalin‐5‐one ( 5 ) was hydroxymethylenated by Claisen ester condensation with ethyl formate to provide the cis ‐configured (2 Z )‐2,3,4,4a,8,8a‐hexahydro‐2‐(hydroxymethylene)‐4a,6‐dimethylnaphthalen‐1(7 H )‐one ( 4 ). In a novel intramolecular Prins reaction with an equimolar amount of p ‐toluenesulfonic acid monohydrate, the ideally preformed precursor 4 cyclized to (1 R *,2 R *,3 S *,7 R *,8 S *)‐2‐hydroxy‐4,8‐dimethyltricyclo[5.3.1.0 3,8 ]undec‐4‐en‐11‐one ( 13 ), comprising the complete carbon framework of the target compound 3 . A Barton–McCombie deoxygenation of the corresponding O ‐phenoxythiocarbonyl derivative, followed by oxidation of the lithium enolate of the resulting ketone 14 with the molybdenum peroxide reagent MoO 5 –pyridine–DMPU, and the face‐selective hydrogenation of the obtained(1 R *,3 S *,7 S *,8 S *)‐3‐hydroxy‐6,8‐dimethyltricyclo[5.3.1.0 3,8 ]undec‐5‐en‐2‐one ( 15 ) concluded the synthesis of the target molecule 3 , which was accompanied by its odorless C‐6 epimer epi ‐ 3 in the ratio 84:16. Both the target structure 3 and its unsaturated precursor 15 possessed pronounced patchouli odors, albeit slightly weaker in threshold than (–)‐patchoulol ( 1 ). This proved the superposition analysis of the templates 1 and 2 to be correct and provided novel insight into the structural requirements of patchouli odorants. As 3 was an intermediate in a total synthesis of rac ‐ 1 , the synthesis also constitutes a new formal total synthesis of racemic patchoulol ( rac ‐ 1 ). (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2006)",10.1002/ejoc.200500975,2006-02-17,0.6508697777091009
European Journal of Organic Chemistry,Efficient and Chirally Specific Synthesis of Phenanthro‐Indolizidine Alkaloids by Parham‐Type Cycloacylation,"Abstract A concise, efficient and modular route involving Parham‐type cycloacylation as the key step has been used to synthesize six enantiopure phenanthro‐indolizidine alkaloids 1a – c . The preparation of enantiomerically pure tylophora alkaloids and their seco analogues on a large‐scale is now feasible. The alcohol intermediates 8a – c , which are difficult to prepare by other synthetic methodologies, have been synthesized by a metallation–cyclization–reduction sequence in excellent yields.",10.1002/ejoc.200900920,2009-11-25,0.6508696022310242
Tetrahedron,A practical synthesis of 4-[(4-methylpiperazin-1-yl)methyl]benzoic acid—the key precursor toward imatinib,,10.1016/j.tetlet.2012.06.107,2012-06-30,0.650850223426869
Angewandte Chemie International Edition,Stereospecific Formal Total Synthesis of Ecteinascidin 743,"A new strategy was designed for the construction of the pentacyclic ring system of ecteinascidin 743. Key features include highly concise routes to the enantiopure, configurationally matched subunit 1, a novel vinylogous Pictet–Spengler cyclization to 2, and a stereospecific epoxidation and regioselective reduction sequence of the C3C4 enamide to secure 3.",10.1002/anie.200503983,2006-02-22,0.6508453951649593
Synlett,"Synthesis of (+)-Methyl Dihydropalustramate and of the Pyrido[1,2-a]azepine Core of Stemona Alkaloids","Starting from a readily available, enantiomerically pure 2,6-disubstituted piperidine the synthesis of pyrido[1,2- a ]azepines was accomplished. Key reactions for the ring closure were a photochemically induced acyl radical addition or a SmI 2 -promoted ketyl radical addition to an α,β-unsaturated ester. En route to the cyclization precursor an epoxidiation/ring opening sequence led to an undesired oxazolidinone which turned out to be useful for the configuration assignment. The compound was successfully converted into (+)-methyl dihydropalustramate.",10.1055/s-0034-1380685,2015-04-30,0.6508329944458214
Angewandte Chemie International Edition,In Pursuit of a Competitive Target: Total Synthesis of the Antibiotic Kendomycin,"Kendomycin is a novel polyketide having a unique quinone methide ansa structure and an impressive biological profile. Herein we provide a chronological overview of the synthetic work towards the title compound. Thus far, over a period of about eight years, eight groups worldwide have published on their synthetic efforts resulting in five total syntheses, one formal synthesis, and a number of fragment syntheses. Most approaches roughly mimic the biogenetic pathway, starting with an aromatic polyphenol subunit to which a polyketide chain is attached. Subsequent key steps include macrocyclization and the formation of the densely substituted tetrahydropyran ring, and then a late-stage oxidation and lactol formation.",10.1002/anie.201000227,2010-06-16,0.6508293514203892
Tetrahedron,"Preparation of ethyl 5(s),6-epoxy-3(r)-(methoxymethoxy)hexanoate: a key chiral intermediate for mevinolin and compactin.",,10.1016/s0040-4039(00)98429-6,1985-01-01,0.6508068225798196
Organic Letters,Total Synthesis of (+)-Thiazinotrienomycin E,"[formula: see text] The first total synthesis of (+)-thiazinotrienomycin E (1), member of a novel class of cytotoxic ansamycin antibiotics, has been achieved. The synthesis features a highly efficient construction of the aromatic fragment 3 incorporating TBS protection of the aniline, a significantly improved synthesis of (-)-19, an intermediate employed in our trienomycins A and F total syntheses, application of the Kocienski modified Julia protocol to elaborate the E,E,E-triene subunit, an efficient union of 3 and (+)-4, and Mukaiyama macrolactamization to access the thiazinotrienomycin macrolide.",10.1021/ol991049g,1999-09-25,0.650806609322818
Synthesis,"Enantioselective Total Synthesis of (+)-Scyphostatin, a Potent and Specific Inhibitor of Neutral Sphingomyelinase","The total synthesis of (+)-scyphostatin, a specific and potent neutral sphingomyelinase inhibitor from a microorganism, was accomplished for the first time starting from d-arabinose and both enantiomers of methyl 3-hydroxy-2-methylpropionate. The method involves (a) stereoselective aldol coupling of a methyl 1,3-dioxolane-4-carboxylate with the Garner aldehyde to establish the asymmetric quaternary carbon center at C4, (b) ring-closing meta­thesis of the resultant diene to construct the cyclohexene ring, (c) Negishi coupling of a vinyl iodide and an alkyl iodide to form the requisite trisubstituted E-alkene, (d) formation of an amide from the cyclohexene segment and the trisubstituted E-alkene fatty acid segment, and (e) stereospecific formation of an epoxide ring from the mesylate of the amide formed from the two segments.",10.1055/s-2007-965893,2007-01-18,0.6507947765979296
European Journal of Organic Chemistry,Protecting‐Group Directed Stereoselective Intramolecular Nozaki–Hiyama–Kishi Reaction: A Concise and Efficient Total Synthesis of Amphidinolactone A,"Abstract A convergent total synthesis of amphidinolactone A, a cytotoxic macrolide from the cultured dinoflagellate Amphidinium sp., is described in 13 linear steps. The key step in the synthetic sequence involves an intramolecular Nozaki–Hiyama–Kishi (NHK) reaction for the construction of the 13‐membered lactone ring by union of two fragments derived from a single chiral epoxide. The stereochemical outcome of the NHK reaction has been supported by computational studies.",10.1002/ejoc.201000565,2010-07-01,0.6507917146085769
Journal of the American Chemical Society,A Concise Synthesis of (−)-Lasonolide A,"Lasonolide A is a novel polyketide displaying potent anticancer activity across a broad range of cancer cell lines. Here, an enantioselective convergent total synthesis of the (-)-lasonolide A in 16 longest linear and 34 total steps is described. This approach significantly reduces the step count compared to other known syntheses. The synthetic strategy utilizes alkyne-bearing substrates as core building blocks and is highlighted by stitching together two similarly complex halves via a key Ru-catalyzed alkene-alkyne coupling and macrolactionization.",10.1021/ja411270d,2013-12-05,0.6507902122277494
Organic Process Research & Development,"Chemical Development of CI-1008, an Enantiomerically Pure Anticonvulsant","Development of a manufacturing process for ( S )-3-(aminomethyl)-5-methylhexanoic acid, an anticonvulsant, is described. Initial preparation employed an Evans chiral alkylation on (4 R,5 S )-4-methyl-3-(1-oxo-4-methylpentyl)-5-phenyl-2-oxazolidinone, using benzyl bromoacetate. Use of tert -butyl bromoacetate proved advantageous for large-scale preparation. Route selection for a low-cost manufacturing process was based on “ideal process” cost projections. Four routes were evaluated in the laboratory. Of the four, two were scaled up in the pilot plant, resulting in selection of a route based on synthesis of racemic 3-(aminomethyl)-5-methylhexanoic acid, followed by resolution with ( S )-(+)-mandelic acid.",10.1021/op9600320,1997-01-01,0.6507779389018451
Tetrahedron,"A novel route from 4-methoxy-5-nitropyrimidine to 3-amino-4-nitropyrazole and pyrazolo[3,4-b]pyrazine",,10.1016/s0040-4039(00)90779-2,1967-01-01,0.6507487544220384
Synlett,"An Improved Synthesis of Cyclopropa[4,5]benzocyclobutene (Rocketene)","All articles of this category A straightforward two-step preparation of cyclopropa-[4,5]benzocyclobutene in 32% yield is described.",10.1055/s-1992-21549,1992-01-01,0.6507301586723754
Organic Process Research & Development,Some Items of Interest to Process R&amp;D Chemists and Engineers,"Synthesis of a MCHr1 AntagonistAntagonism of the melanin-concentrating hormone (MCH) receptor could provide a means to control overeating/obesity in people since this hormone is implicated in the feeding behavior of mammals.Andersen and co-workers at Amgen describe their efforts towards a scalable synthesis of AMG076, a compound that was identified as a potent MCHr1 antagonist (J.Org.Chem.2007, 72, 9648-9655).A Robinson annulation between N-benzyl-4-piperidone (pyrrolidine enamine) and 3-pentene-2-one in 1,4-dioxane at 90 °C gave the annulated product as a mixture of diastereomers, from which the desired compound was separated using a tartrate salt resolution (28% overall yield from N-benzyl-4-piperidone). Hydrogenation of the desired enone yielded the ketone fragment necessary for coupling with an arylhydrazine in a Fischer indole synthesis.The indole synthesis afforded an 8:1 mixture of regioisomers, from which the desired (linear) product could be separated via a H 3 PO 4 salt formation/salt break sequence in 67% overall yield from the starting ketone.The optimal end game featured a reductive amination of a lactol under heterogeneous catalytic hydrogenation conditions.Multikilogram experimental details are provided. Synthesis of 4,4-Disubstituted Cyclohexane β-Keto EstersA one-pot method for the synthesis of 4,4-disubstituted cyclohexane β-keto esters from benzylic nitriles or esters is described by Julian, Powers, and co-workers at Amgen (J.Org.Chem.2007, 72, 7455-7458).The process relies on a tandem double Michael addition-Dieckmann condensation reaction sequence between the ester or nitrile substrates and 2 equiv of methyl acrylate, which results in the formation of three discrete carbon-carbon bonds in a single pot, including a quaternary center.Although similar chemistry is described in the literature, the authors note that the existing procedures suffered from reproducibility problems and safety issues (95% NaH used as base).By substituting KOt-Bu as the base the authors were able to conduct the double Michael-Dieckmann sequence in one pot in good overall yield.",10.1021/op700278r,2008-01-01,0.6507260284251412
Journal of Organic Chemistry,Modular Total Synthesis of Archazolid A and B,"A modular total synthesis of the potent V-ATPase inhibitors archazolid A and B is reported. The convergent preparation was accomplished by late-stage diversification of joint intermediates. Key synthetic steps involve asymmetric boron-mediated aldol reactions, two consecutive Still-Gennari olefinations to set the characteristic (Z,Z)-diene system, a Brown crotyboration, and a diastereoselective aldol condensation of highly elaborate intermediates. For macrocyclization, both an HWE reaction and a Heck coupling were successfully employed to close the 24-membered macrolactone. During the synthetic campaign, a generally useful protocol for an E-selective Heck reaction of nonactivated alkenes and a method for the direct nucleophilic displacement of the Abiko-Masamune auxiliary with sterically hindered nucleophiles were developed. The expedient and flexible strategy will enable further SAR studies of the archazolids and more detailed evaluations of target-inhibitor interactions.",10.1021/jo901565n,2009-09-09,0.6507180132314283
Green Chemistry,Application of biocatalysis towards asymmetric reduction and hydrolytic desymmetrisation in the synthesis of a β-3 receptor agonist,"Chemoenzymatic syntheses of two key intermediates in the preparation of a potent β-3 receptor agonist 1 are described. A lipase-catalysed hydrolytic desymmetrisation is employed in a new synthesis of intermediate 7, which avoids the use of alkyl-tin reagents. A second biotransformation delivers chiral chlorohydrin 5 from its parent ketone in greater enantiomeric excess than the previously-described Noyori-reduction process. A brief discussion of the enantioselectivity of a set of single-point mutants of Sporobolomyces salmonicoloraldehyde reductase in this bioreduction is also presented.",10.1039/c1gc15694b,2011-01-01,0.650715729744615
Angewandte Chemie International Edition,Total Synthesis of (±)‐Phyllantidine: Development and Mechanistic Evaluation of a Ring Expansion for Installation of Embedded Nitrogen‐Oxygen Bonds,"The development of a concise total synthesis of (±)-phyllantidine (1), a member of the securinega family of alkaloids containing an unusual oxazabicyclo[3.3.1]nonane core, is described. The synthesis employs a unique synthetic strategy featuring the ring expansion of a substituted cyclopentanone to a cyclic hydroxamic acid as a key step that allows facile installation of the embedded nitrogen-oxygen (N-O) bond. The optimization of this sequence to effect the desired regiochemical outcome and its mechanistic underpinnings were assessed both computationally and experimentally. This synthetic approach also features an early-stage diastereoselective aldol reaction to assemble the substituted cyclopentanone, a mild reduction of an amide intermediate without N-O bond cleavage, and the rapid assembly of the butenolide found in (1) via use of the Bestmann ylide.",10.1002/anie.202003829,2020-04-09,0.6507011119584575
Journal of Organic Chemistry,A Total Synthesis of FK-506<sup>1</sup>,"A total synthesis of FK-506 (1) is presented. The synthesis features a highly convergent approach utilizing a block coupling strategy. Top and bottom half sections of the molecule are coupled by addition of a vinyl cuprate with a spiroenone. The alpha-allyl aldol functionality is revealed by a reductive opening of the spiroenone system. The labile alpha,beta-diketoamide hemiketal portion of the molecule is prepared by a late stage generation and oxidation of a masked enediol. Top and bottom half segments are themselves derived by coupling of smaller subunits, resulting in a very convergent route.",10.1021/jo951646q,1996-01-01,0.6506949377894365
Journal of the American Chemical Society,Total Synthesis of (+)-Chinensiolide B via Tandem Allylboration/Lactonization,"The chinensiolides are a family of guaiane type alpha-methylene gamma-lactone natural products recently isolated from Ixeris chinensis Nakai, a plant used in Chinese folk medicine. The first enantioselective total synthesis of (+)-chinensiolide B was accomplished in 15 steps for the longest linear sequence with an overall yield of 6.7% starting from inexpensive and readily available (R)-carvone. A highly stereoselective and E/Z-selective tandem allylboration/lactonization reaction between two highly functionalized partners was exploited as a key step. The synthesis also highlights several solutions to chemoselectivity issues arising from the reactive alpha-methylene gamma-lactone. For instance, a ring-closing metathesis formed the requisite seven-membered ring in a chemoselective fashion while avoiding the reactivity of the conjugated alpha-methylene unit.",10.1021/ja9104478,2010-01-12,0.6506925393047264
Journal of the American Chemical Society,A Short Total Synthesis of (±)-Epimeloscine and (±)-Meloscine Enabled by a Cascade Radical Annulation of a Divinylcyclopropane,"The first stereoselective synthesis of epimeloscine has been accomplished in 13 total steps with a longest linear sequence of 10 steps. The core of the synthesis takes only five steps, the key ones being acylation, stereoselective tandem radical cyclization of a divinylcyclopropane to make two rings, and group-selective ring-closing metathesis of the resulting divinylcyclopentane to make the last ring.",10.1021/ja2042854,2011-06-13,0.6506505971485467
Journal of the American Chemical Society,"Direct Chemical Synthesis of the β-Mannans:  Linear and Block Syntheses of the Alternating β-(1→3)-β-(1→4)-Mannan Common to <i>Rhodotorula </i><i>glutinis</i>, <i>Rhodotorula </i><i>mucilaginosa</i>, and <i>Leptospira </i><i>biflexa</i>","Two stereocontrolled syntheses of a methyl glycoside of an alternating beta-(1-->4)-beta-(1-->3)-mannohexaose, representative of the mannan from Rhodotorula glutinis, Rhodotorula mucilaginosa, and Leptospira biflexa, are described. Both syntheses employ a combination of 4,6-O-benzylidene- and 4,6-O-p-methoxybenzylidene acetal-protected donors to achieve stereocontrolled formation of the beta-mannoside linkage. The first synthesis is a linear one and proceeds with a high degree of stereocontrol throughout and an overall yield of 1.9%. The second synthesis, a block synthesis, makes use of the coupling of two trisaccharides, resulting in a shorter sequence and an overall yield of 4.4%, despite the poor selectivity in the key step.",10.1021/ja0471931,2004-10-22,0.6506496728802246
Journal of Organic Chemistry,Application of Furanyl Carbamate Cycloadditions Toward the Synthesis of Hexahydroindolinone Alkaloids,"A convenient synthesis of various substituted hexahydroindolinones has been achieved by an intramolecular Diels--Alder cycloaddition reaction (IMDAF) of furanyl carbamates bearing tethered alkenyl groups. The initially formed [4 + 2]-cycloadduct undergoes nitrogen-assisted ring opening followed by deprotonation of the resulting zwitterion to give the rearranged ketone. The stereochemical outcome of the IMDAF cycloaddition has the sidearm of the tethered alkenyl group oriented syn with respect to the oxygen bridge. A synthetic route to (+/-)-mesembrane and (+/-)-crinane was accomplished using this methodology. It was possible to carry out a stereoselective reduction of the initially formed hexahydroindolinone ring to produce the cis-3a-aryl-hydroindole skeleton. A related [4 + 2]-cycloaddition/rearrangement sequence was also used for a formal synthesis of the Chinese ornamental orchid (+/-)-dendrobine. The tricyclic alkaloid core was formed stereoselectivity from the thermolysis of N-[(2-methyl-2-cyclopentenyl)methyl]-N-(4-isopropyl-furan-2-yl)carbamic acid tert-butyl ester. Kende's advanced intermediate 33 was prepared in seven additional steps by standard transformations, thereby completing a formal synthesis of (+/-)-dendrobine.",10.1021/jo010020z,2001-04-04,0.65064110183707
Synlett,Total Synthesis of (-)-Neplanocin A from L-Ribulose,All articles of this category (-)-Neplanocin A ( 9 ) has been synthesized from L-ribulose ( 1 ) in 14 steps and in 15 % overall yield. The key step involves an intramolecular nitrone [2+3] cycloaddition reaction.,10.1055/s-1991-20924,1991-01-01,0.6506390643184848
Organic Letters,"Synthesis of the Isoxazolo[4,3,2-<i>de</i>]phenanthridinone Moiety of the Parnafungins","A practical route to the labile tetracyclic isoxazolo[4,3,2-de]phenanthridinone moiety of the antifungal parnafungins has been developed. Zinc reduction of a methyl 2'-hydroxymethyl-2-nitro-3-biphenylcarboxylate, which was prepared by a Suzuki coupling, afforded a benzisoxazolone that was treated with MsCl and base to generate the labile tetracyclic ring system in 37-47% yield. This compound decomposes to the phenanthridine in CDCl(3) and the phenanthridine N-oxide in aqueous base.",10.1021/ol901054r,2009-06-04,0.6506340043467563
European Journal of Organic Chemistry,Androstanes with Modified Carbon Skeletons,"Abstract Four sterane hydrocarbons were prepared for comparison with fossil organic biomarkers in geological samples from Oman. 17β‐Methylestrane was prepared in six steps (36 % overall yield) from estrone methyl ether. Key steps of this sequence were a Wittig olefination and Birch reduction of the A‐ring. 17β‐Methylandrostane was obtained in four steps (85 % overall yield) from trans ‐androsterone by four functional group interconverting reactions, including a Wittig olefination. 17β‐Methyl‐ and 2α‐methyl‐A‐ nor ‐5α‐androstanes (14 and 15 % overall yields, respectively) were also prepared from trans ‐androsterone. Key steps were the thallium trinitrate mediated ring contractions of A‐ring ketones to A‐ nor ‐2‐carboxylic acids. Defunctionalization in the four syntheses was achieved by catalytic hydrogenation, Huang‐Minlon reduction, Barton decarboxylation, and Bu 3 SnH‐mediated reduction of a chloromethyl group, respectively.",10.1002/ejoc.201100390,2011-06-17,0.6506290549469395
Organic Process Research & Development,"Practical Synthesis of the Bicyclic Darunavir Side Chain: (3<i>R</i>,3a<i>S</i>,6a<i>R</i>)-Hexahydrofuro[2,3-<i>b</i>]furan-3-ol from Monopotassium Isocitrate","High Resolution Image Download MS PowerPoint Slide A practical synthesis of (3 R,3a S,6a R )-hexahydrofuro[2,3- b ]furan-3-ol—a key intermediate in the synthesis of darunavir—from monopotassium isocitrate is described. The isocitric acid salt, obtained from a high-yielding fermentation fed by sunflower oil, was converted in several steps to a tertiary amide. This amide, along with the compound’s ester functionalities, was reduced with lithium aluminum hydride to give, on acidic workup, a transient aminal-triol. This was converted in situ to the title compound, the bicyclic acetal furofuranol side chain of darunavir, a protease inhibitor used in treatment of HIV/AIDS. Key to the success of this process was identifying an optimal amide that allowed for complete reaction and successful product isolation. N -Methyl aniline amide was identified as the most suitable substrate for the reduction and the subsequent cyclization to the desired product. Thus, the side chain is produced in 55% overall yield from monopotassium isocitrate.",10.1021/acs.oprd.6b00377,2016-12-14,0.6506190092149146
Tetrahedron,Stereoselective synthesis of the α-glucosidase inhibitor nectrisine,,10.1016/j.tetlet.2003.08.030,2003-09-16,0.6506158760890298
Tetrahedron,N-acyldihydropyridones as synthetic intermediates. synthesis of (±)-septicine and (±)-tylophorine.,,10.1016/s0040-4039(00)79426-3,1991-10-01,0.6506013008145236
Synlett,Enantioselective Allyltitanation. Synthesis of (+)-Sedamine,"All articles of this category A total synthesis of (+)-sedamine was accomplished from benzaldehyde in 11 steps with an overall yield of 20%, using two enantioselective allyltitanations and a ring-closing metathesis as the key steps. enantioselective allylation - alkaloids - titanium - piperidines - (+)-sedamine",10.1055/s-2000-7625,2000-01-01,0.6505999836469715
European Journal of Organic Chemistry,Synthesis of Deuterated Mevalonolactone Isotopomers,"Abstract A synthetic route was developed for the preparation of deuterated mevalonolactones. Using low‐cost deuterated reagents, this route allows for the independent introduction of deuterium labeling into any carbon position or into any combination of positions. Following this approach, the synthesis of [6,6,6‐ 2 H 3 ]mevalonolactone, [4,4,6,6,6‐ 2 H 5 ]mevalonolactone, [5,5‐ 2 H 2 ]mevalonolactone, [5,5,6,6,6‐ 2 H 5 ]mevalonolactone, and [2,2,6,6,6‐ 2 H 5 ]mevalonolactone is described.",10.1002/ejoc.201100188,2011-05-05,0.6505859635666864
Synlett,Total Synthesis of Altenusin and Alterlactone,"The resorcylic lactone alterlactone, a mycotoxin produced by alternaria sp., was synthesized for the first time. The total synthesis was achieved in nine steps with 69% yield starting with acetal-protected phloroglucinic acid and 6-bromopiperonal, where the longest linear sequence consists of five steps. Key step is a ­Suzuki coupling used for the construction of the central biaryl bond. When the final deprotection with cleavage of benzyl ethers (yielding unprotected alterlactone) was performed in a less polar solvent the biaryl mycotoxin altenusin was obtained.",10.1055/s-0031-1290135,2012-01-19,0.6505842512937413
Organic Process Research & Development,Hindered Biaryl Bond Construction and Subsequent Diastereomeric Crystallization to Produce an Atropisomeric Covalent KRAS<sup>G12C</sup> Inhibitor ARS-2102,"A scaleup route for a first-generation covalent KRAS G12C inhibitor ARS-2102 was devised, featuring an “early cross-coupling” strategy to construct the tetra-substituted atropisomeric biaryl scaffold. An iterative diastereomeric recrystallization enabled an effective chiral resolution of key intermediate 24 . A global deprotection followed by chemoselective functionalization afforded ARS-2102 in excellent yield and diastereomeric enrichment. This chromatography-free sequence was successfully executed on kilogram scale.",10.1021/acs.oprd.2c00335,2022-12-28,0.650581222669347
Angewandte Chemie International Edition,A Highly Efficient Synthesis of Lamellarins K and L by the Michael Addition/Ring‐Closure Reaction of Benzyldihydroisoquinoline Derivatives with Ethoxycarbonyl‐<i>β</i>‐nitrostyrenes,"Alkaloid achievement: Lamellarins, a new class of potential nontoxic inhibitors of HIV-1 integrase that are also responsible for multidrug-resistance reversal in cancer cell lines, could be synthesized in three chemical steps and in 60 % overall yields from two simple starting materials (see scheme). The key step in the convergent synthetic approach involved the novel Michael addition/ring-closure reaction to give the pyrrole core and the ester group required for subsequent lactonization in one step.",10.1002/anie.200352043,2004-02-02,0.6505649627222805
Tetrahedron,Synthesis of an amidine pseudo-(1→6)-dimannoside and evaluation as a glycosidase inhibitor,,10.1016/0040-4039(95)01002-y,1995-07-01,0.6505613398634357
Tetrahedron,Synthesis of an Amidine Pseudo-(1 → 6)-dimannoside and Evaluation as a Glycosidase Inhibitor,,10.1016/00404-0399(50)1002y-,1995-07-17,0.6505613398634357
Tetrahedron,"A flexible route to immunosuppressive agent FR252921. Asymmetric total synthesis of its (13R,14R,19R)-isomer",,10.1016/j.tetlet.2006.09.169,2006-11-08,0.6505526221260779
European Journal of Organic Chemistry,Identification of a Fossil Sterane Biomarker in Crude Oil – an Androstane with a Modified Carbon Skeleton,"Abstract Three constitutional isomers of androstane were prepared for comparison with three unknown fossil C 19 H 32 organic biomarkers (“19A”, “19B”, and “19C” in elution order) in geological samples from Oman. 3β‐Methyl‐A‐ nor ‐androstane was prepared in six steps (8 % overall yield) from testosterone. The key steps of this sequence were an Eschenmoser fragmentation and recyclization of the A ring. A mixture of four stereoisomers of 3‐methyl‐A‐ nor ‐androstane (4 % overall yield) was prepared by ionic hydrogenation of the olefin after A‐ring recyclization in three steps. 17‐Methyl‐18‐ nor ‐androstane was synthesized in four steps as a mixture of isomers (58 % overall yield) from dihydrotestosterone with a Wagner–Meerwein shift of the 13β‐methyl group to C‐17 as the key step. Pure 17β‐ and 17α‐methyl‐18‐ nor ‐13α‐androstane (4 and 2 % overall yield, respectively) were obtained in three additional steps after α‐oxidation of the Wagner–Meerwein rearrangement product and subsequent reduction. The synthesis of 18‐ nor ‐D‐ homo ‐13β‐androstane (12 % yield over seven steps from dihydrotestosterone) involved oxidative cleavage of the C–C double bond in the Wagner–Meerwein rearrangement product from the previous synthesis and subsequent recyclization of the D ring followed by reduction. The relative configurations of all final products were confirmed by X‐ray crystallography. A comparison of the synthetic standards with the saturated hydrocarbon fraction of an Oman crude oil by gas chromatography (GC–MS) coinjection on three different GC columns and comparison of mass spectra revealed that unknown compound 19C is 18‐ nor ‐D‐ homo ‐13β,14α‐androstane, whereas the isomeric 3‐methyl‐A‐ nor ‐androstanes and 17‐methyl‐18‐ nor ‐androstanes elute close to 19A and 19B, respectively, but do not match the unknowns.",10.1002/ejoc.201300788,2013-07-26,0.6504957146573499
Organic Letters,General Approach for the Synthesis of Sarpagine/Ajmaline Indole Alkaloids. Stereospecific Total Synthesis of the Sarpagine Alkaloid (+)-Vellosimine,[reaction: see text] (+)-Vellosimine has been synthesized enantiospecifically in 27% overall yield from commercially available D-(+)-tryptophan methyl ester via the asymmetric Pictet-Spengler reaction and a stereocontrolled intramolecular palladium-coupling reaction as key steps.,10.1021/ol000095+,2000-06-17,0.6504882179582332
Organic Process Research & Development,Synthesis of the Hydrazinyl Pyridine Intermediate: Phase-Appropriate Delivery,"A two-step synthesis of an intermediate for a drug-candidate, 3-fluoro-2-hydrazinyl-5-(1-methyl-1 H -pyrazol-4-yl)pyridine ( 1 ), was developed and optimized according to the strategic priorities of the program. The bond disconnection remained unchanged from the initial route to the scale-up routes; however, the process evolved as the program’s priorities progressed. Speed, securing the raw material supply chain, and cost were all factors considered during development. The strategies to enable multikilogram deliveries are highlighted in this report.",10.1021/acs.oprd.7b00172,2017-07-24,0.6504779342321877
Journal of Organic Chemistry,Application of a 6π-1-Azatriene Electrocyclization Strategy to the Total Synthesis of the Marine Sponge Metabolite Ageladine A and Biological Evaluation of Synthetic Analogues,"A 12-step synthesis of the angiogenesis inhibitory marine metabolite ageladine A is reported. The key steps include a 6pi-1-azatriene electrocyclization for formation of the pyridine ring and a Suzuki-Miyaura coupling of N-Boc-pyrrole-2-boronic acid with a chloroimidazopyridine. In addition, an assessment of the biological activity of a variety of synthetic analogues of ageladine A prepared during this synthesis is described.",10.1021/jo0707232,2007-06-01,0.6504724880080034
Tetrahedron,Synthesis of bicyclic β-lactamase inhibitor relabactam derivatives from a relabactam intermediate,,10.1016/j.tetlet.2017.06.018,2017-06-07,0.6504707949464442
European Journal of Organic Chemistry,First Total Synthesis of Pinolide,"Abstract The first total synthesis of pinolide, a nonsymmetrical ten‐membered macrocyclic, is described starting from readily available (–)‐tartaric and L ‐ascorbic acid. The key synthetic steps include Barbier allylation, Yamaguchi esterification and ring‐closing metathesis (RCM) reactions. The synthetic strategy has been successful for the construction of the ten‐membered core skeleton. A facile and convergent approach enabled the incorporation of all the four stereogenic centers present in the molecule.",10.1002/ejoc.201300587,2013-09-05,0.650454954373577
European Journal of Organic Chemistry,"Synthesis of Posticlure [(6Z,9Z,11S,12S)-11,12-Epoxyhenicosa-6,9-diene], the Female Sex Pheromone of Orgyia postica","Starting from commercially available (E)-2-dodecenoic acid, posticlure [(6Z,9Z,11S,12S)-11,12-epoxyhenicosa-6,9-diene (1)], the female sex pheromone of the tussock moth (Orgyia postica), was synthesized in 25% overall yield (6 steps) by employing Sharpless asymmetric dihydroxylation as the key step. Its (11R,12R)-isomer as well as its racemate were also synthesized.",10.1002/1099-0690(200112)2001:24<4635::aid-ejoc4635>3.0.co;2-j,2001-12-01,0.6503906164764501
Synlett,Enantioselective Total Synthesis of (-)-Dibromophakellstatin,"The antitumor active pyrrole-imidazole alkaloid (-)-dibromophakellstatin from the marine sponge Phakellia mauritiana was synthesized enantioselectively in ten steps, starting from ­hydroxyproline. The key step is the diastereoselective three-component imidazolidinone annulation to a chiral dipyrrolopyrazinone. Deoxygenation of a hydroxyphakellstatin precursor was achieved by Appel reaction, followed by reduction with SmI2.",10.1055/s-2007-986664,2007-09-12,0.6503861891488771
Organic Process Research & Development,Short Synthesis of a Proline Amide Orexin Receptor Antagonist on the Pilot Plant Scale,"A three-step fully telescoped synthesis of an N -sulfonyl proline amide, a nonpeptide antagonist of human orexin receptors, is described. The process development from the medicinal chemistry route up to the 240 kg production of 1 is discussed with a focus on an economical and efficient amide bond formation and identification of a new polymorph. The routes are compared using green metrics.",10.1021/op500277s,2014-11-03,0.6503768313953743
Tetrahedron,"A novel route to 2,4-dianilino-substituted pyrimidines",,10.1016/j.tetlet.2009.11.094,2009-11-27,0.6503738978740244
Tetrahedron,Azabicyclic Urethane Rearrangements. I. A Novel Route to Substituted Azabicyclo[3.2.1]oct-2-enes.,,10.1016/s0040-4039(01)87588-2,1973-01-01,0.6503738978740244
Journal of Organic Chemistry,"Enantioselective Synthesis of (+)-Cryptophycin 52 (LY355703), a Potent Antimitotic Antitumor Agent","A highly enantioselective and convergent synthesis of cryptophycin 52 (2), an exceedingly potent cytotoxic agent, is described. Cryptophycin 52, a synthetic variant of the cryptophycin family, is currently undergoing clinical trials. The synthesis is convergent and involves assembly of three fragments, phenyl hexenal 3, d-tyrosine phosphonate 4, and protected beta-amino acid derivative 5. The synthesis of fragment 3 involves an efficient and stereocontrolled construction of both stereogenic centers at C-3 and C-4 by cleavage of a substituted tetrahydrofuran ring via an acyloxycarbenium ion intermediate. Both of these stereogenic centers were derived from optically active 4-phenylbutyrolactone, synthesized enantioselectively by Corey-Bakshi-Shibata reduction.",10.1021/jo035077v,2003-11-14,0.6503731740616848
Journal of Organic Chemistry,"Biomimetic Total Synthesis of Ervitsine and Indole Alkaloids of the Ervatamine Group <i>via</i> 1,4-Dihydropyridines","Addition of the enolate derived from 2-acetylindole 1a to pyridinium salt 2 followed by in situ trapping of the initially formed 1,4-dihydropyridine 3a with Eschenmoser's salt gives tetracycle 5a . Subsequent elaboration of the exocyclic methylene and E -ethylidene substituents leads to N a -methylervitsine ( 17a ). A similar sequence from the N a -protected 2-acetylindole 1c establishes the first total synthesis of the 2-acylindole alkaloid ervitsine. Alternatively, dihydropyridine 3a is trapped with BrSePh to give the tetracyclic selenide 7a, which is then converted to N a -methylervitsine by way of selenoxide 20 . The synthesis of the alkaloids of the ervatamine group starts with the addition of the enolate derived from 2-acetyl-1-benzylindole ( 1g ) to pyridinium salt 24 and the conversion of the resulting 1,4-dihydropyridine to 3,5-diacylated dihydropyridine 26g . Chemoselective reduction of the vinylogous amide moiety of 26g, followed by deprotection of the indole ring and LiEt 3 BH reduction leads to diol 37b . On sequential treatment with Eschenmoser's salt, methyl iodide, NaCNBH 3, and MnO 2, 37b is converted to the tetracyclic 2-acylindole 39, from which the first total synthesis of 19,20-didehydroervatamine and 20-epiervatamine is accomplished by manipulation of the 1-hydroxyethyl chain. The above syntheses can be considered as biomimetic, as cyclization of the key intermediates I and II mimics the key steps of the biosynthesis of the title alkaloids.",10.1021/jo9623301,1997-05-01,0.6503470373866959
Organic Letters,Concise Total Synthesis of (−)-Auxofuran by a Click Diels–Alder Strategy,"The first synthesis of auxofuran, a newly discovered auxin-like signaling molecule of streptomycetes, has been achieved in seven steps and 59% overall yield from commercial starting materials. Central to the synthetic route is a click-unclick Diels-Alder cycloaddition/cycloreversion regimen enabling rapid access to an advanced intermediate from an unactivated alkyne.",10.1021/ol402345x,2013-09-06,0.6503432885673675
Tetrahedron,Studies directed toward the synthesis of (+)-mycotrienin I. Asymmetric synthesis of the C9N21 aromatic synthon,The asymmetric synthesis of the C9N21 fragment of (+)-mycotrienin I is described employing chiral allylsilane bond construction methodology for the installation of the C12C13 absolute stereochemical relationships. In this convergent synthesis the construction of the C9C16 and C17N21 aromatic synthon subunits and their coupling through a lithio dithiane alkylation strategy are detailed.,10.1016/0040-4039(94)02427-d,1995-02-01,0.6503084117592777
Tetrahedron,Acylation of β-oxoalkyltetracarbonylferrate(o). A novel route to enol ester,,10.1016/s0040-4039(00)91484-9,1975-01-01,0.6503068510082836
Organic Letters,Synthesis of the Tetracyclic Core of the Daphlongeranines,"High Resolution Image Download MS PowerPoint Slide The first synthesis of the tetracyclic core of the daphlongeranine natural product family is reported. Containing a tricyclic core unique to this subfamily of the Daphniphyllum alkaloids and featuring two quaternary carbons, this 11-step synthetic route featured the application of a three-step spirocyclization strategy and development of a new intramolecular Pd-catalyzed cyclization reaction. Additionally, the route included the application of an XAT-initiated Giese addition and demonstration of an enantioselective synthesis of the bicyclic core.",10.1021/acs.orglett.5c03362,2025-10-07,0.6502994047716885
Journal of Organic Chemistry,Stereoselective Synthesis of a Potent Thrombin Inhibitor by a Novel P2−P3 Lactone Ring Opening,"The concise synthesis of a potent thrombin inhibitor was accomplished by a mild lactone aminolysis between an orthogonally protected bis-benzylic amine and a diastereomerically pure lactone. The lactone was synthesized by the condensation of l-proline methyl ester with an enantiomerically pure hydroxy acid, which in turn was synthesized by a highly stereoselective (>500:1 er) and productive (100,000:1, S/C) enzymatic reduction of an alpha-ketoester. In addition, a second route to the enantiomerically pure lactone was accomplished by a diastereoselective ketoamide reduction.",10.1021/jo035794p,2004-05-01,0.650287668015666
Tetrahedron,"An efficient asymmetric synthesis of (2S,3S)-3-trifluoromethylpyroglutamic acid",,10.1016/s0040-4039(97)01054-x,1997-07-01,0.6502856879382688
Organic Letters,A Six-Step Asymmetric Synthesis of (+)-Hyperaspine,"[reaction: see text] The ladybird alkaloid, (+)-hyperaspine, has been synthesized in a concise and highly stereoselective manner. The total synthesis was accomplished in six steps and 21% overall yield.",10.1021/ol052068v,2005-10-21,0.6502764572742383
Organic Process Research & Development,Improved Synthesis and Impurity Control Strategy of Penehyclidine Hydrochloride,"A scalable process for the synthesis of high-purity penehyclidine hydrochloride (99.9% by HPLC area %) without purification by fractional distillation has been developed with significantly improved overall yield, where a robust and cost-effective Corey–Chaykovsky reaction was successfully explored. Critical parameters of each step and process-related impurities were identified, and all impurities reported in this work have been independently synthesized, which could promote the understanding of the impurity profile and potentially boost the upgrade of the drug standard.",10.1021/acs.oprd.3c00297,2024-01-05,0.6502716717856906
Organic Process Research & Development,"Practical and Scalable Method for Manufacturing AZD4604, A Potent and Selective JAK1 Inhibitor","The development of a scalable process for the manufacture of a potent and selective JAK1 inhibitor intended for the inhaled treatment of asthma is described. The initial milligram-scale synthetic protocols were unsuitable for larger-scale synthesis, which led to a systematic evaluation of the reaction conditions to identify the optimized reaction conditions for the Suzuki/Buchwald–Hartwig coupling, deprotection of the tosyl group, chemoselective nitro-reduction, and developing mild conditions for the amide coupling of a sensitive amino acid. This work also highlights mitigating critical issues associated with the synthesis of poorly soluble compounds, slurry-to-slurry metal-catalyzed coupling protocols. The optimized amide coupling conditions using chiral amino acid produced the desired active pharmaceutical ingredient (API) in high overall yield and good high-performance liquid chromatography (HPLC) purity.",10.1021/acs.oprd.3c00077,2023-06-15,0.6502561239408535
Angewandte Chemie International Edition,Concise Total Synthesis of Dioncophylline E through an <i>ortho</i>‐Arylation Strategy,"The first total synthesis of the potent antimalarial 7,3'-linked naphthylisoquinoline alkaloid dioncophylline E (1) has been completed. The synthesis proceeds in 12 steps (longest linear sequence) and in 15 % overall yield. Key transformations include an ortho-arylation of a naphthol with an aryllead triacetate to construct the sterically hindered biaryl bond, and a three-step sequence to stereoselectively generate the trans-1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline moiety.",10.1002/anie.201701136,2017-05-04,0.6502525772926406
Organic Letters,Synthesis of Tetrahydroisoquinocarbazoles via C-2 Alkylation of Indoles with 2-Alkoxycyclopropanoate Esters,"A concise method for the synthesis of several tetrahydroisoquinocarbazole derivatives is reported, where the core is prepared in six steps from tryptophol in 51% overall yield. The pentacyclic analogs are constructed via a dipolar C-2 alkylation of a 3-substituted indole with a 2-alkoxycyclopropanoate ester and a SmBr(2)-HMPA mediated ketyl-alkene ring closure.",10.1021/ol900937f,2009-06-09,0.6502234041794545
Journal of Organic Chemistry,Asymmetric Total Syntheses of (−)-Hedycoropyrans A and B,"The first and asymmetric total synthesis of (-)-hedycoropyrans A (1) was accomplished in 18 steps with 5.4% overall yield. The key features of our strategy include (1) construction of the unusual trans-2-aryl-6-alkyl tetrahydropyran core via Achmatowicz rearrangement, Zn-mediated reductive deoxygenation, and Heck-Matsuda coupling reaction, and (2) installation of 3,4-anti-dihydroxy from the corresponding 3,4-syn-dihydroxy THP through chemo- and regioselective IBX oxidation and Evans-Saksena reduction. In addition, C2 epimerization of (-)-hedycoropyan A (1) under the acidic condition furnished (-)-hedycoropyan B (2) with 71% yield. This finding might suggest the biogenetic origin of hedycoropyran B.",10.1021/acs.joc.6b02738,2016-12-28,0.6502163505961468
Journal of Organic Chemistry,A Flexible Synthesis of the Phytoprostanes B <sub>1</sub> Type I and II,Syntheses of the enantiomerically pure phytoprostanes B(1) type I and II are described starting from furfural and n-propylfuran. Key steps include the preparation of the Freimanis (+/-)-hydroxycyclopentenone and Wittig coupling using chiral phosphonium salts.,10.1021/jo048179+,2005-01-07,0.6501795043445179
Organic Letters,A Scalable Total Synthesis of (−)-Nakadomarin A,"The convergent total synthesis of the manzamine alkaloid (−)-nakadomarin A ( 1 ) is described. The retrosynthetic analysis recognized spirocycle 3, assembled via an organocatalyst-promoted Michael addition/cyclization between bicyclic lactam 4 and furan aldehyde 5, both accessible from achiral starting materials and on a multigram scale. Lactam 4 is assembled through an S N 2′/reduction/Staudinger/retro-aza-Claisen sequence on scale. After spirocyclization, the synthesis of nakadomarin is completed in only six steps.",10.1021/acs.orglett.6b03137,2016-11-11,0.650173592299298
Organic Letters,"Toward the Total Synthesis of Goniodomin A, An Actin-Targeting Marine Polyether Macrolide: Convergent Synthesis of the C15−C36 Segment","Stereoselective convergent synthesis of the C15-C36 segment of goniodomin A, an actin-targeting marine polyether macrolide natural product, has been achieved. The present synthesis features palladium(0)-catalyzed, copper(I)-mediated Liebeskind-Srogl cross-coupling as the fragment assembly process.",10.1021/ol902217q,2009-10-26,0.650148286673343
Journal of Organic Chemistry,Highly <i>E</i>-Selective and Effective Synthesis of Antiarthritic Drug Candidate S-2474 Using Quinone Methide Derivatives,"We have developed an efficient and E-selective synthesis of an antiarthritic drug candidate (E)-(5)-(3,5-di-tert-butyl-4-hydroxybenzylidene)-2-ethyl-1,2-isothiazolidine-1,1-dioxide (S-2474; 1), in which alpha-methoxy-p-quinone methide is used as a key intermediate. alpha-Methoxy-p-quinone methide was revealed to be an equivalent to a p-hydroxy protected benzaldehyde. It reacts smoothly with alpha-sulfonyl carbanion to give 1,6-addition intermediates, which can be further processed to provide S-2474 directly in the presence of a base. This procedure gives S-2474 as an almost single isomer on the benzylidene double bond in excellent yield and thus is a very practical method adaptable to large-scale synthesis. The detailed mechanistic aspects are studied and discussed.",10.1021/jo0106795,2001-12-07,0.6501441942037741
Organic Letters,Highly Efficient Synthesis of Ketoheptoses,"A reliable, facile, high overall yielding and diastereoselective synthesis of ketoheptoses was developed and applied for preparation of the two most diabetogenic ketoheptoses as well as in a modified version for the synthesis of kamusol.",10.1021/ol2012764,2011-06-14,0.650138005115402
Organic Letters,A Stereoselective Synthesis of (−)-Viridiofungin A Utilizing a TiCl<sub>4</sub>-Promoted Asymmetric Multicomponent Reaction,A stereoselective synthesis of (-)-viridiofungin A is described. The convergent synthesis utilized a unique highly diastereoselective multicomponent reaction between optically active phenyldihydrofuran and an α-ketoester to provide two chiral centers including a quarternary carbon center in a single step. Other key steps include an acyloxycarbonium ion-mediated tetrahydrofuran ring-opening reaction and a Julia-Kocienski olefination.,10.1021/ol203093g,2011-12-23,0.6501305409598583
Organic Process Research & Development,A Large-Scale Synthesis of Potent Glucokinase Activator MK-0941 via Selective <i>O</i>-Arylation and <i>O</i>-Alkylation,"An efficient, practical preparation of MK-0941, a potent glucokinase activator, is described. Keys to the success of the synthesis are a highly selective mono- O -arylation of methyl 3,5-dihydroxybenzoate with 2-ethanesulfonyl-5-chloropyridine and the choice of a proper protective group for the subsequent S N 2 O -alkylation. With the thorough understanding of the origins and fate of in-process impurities, the second-generation robust synthesis with a minimum number of operations reproducibly prepares MK-0941 in 56% overall yield with >99% purity.",10.1021/op200068c,2011-05-04,0.6501260872994975
Organic Letters,Iodocyclization and Prins-Type Macrocyclization: An Efficient Formal Synthesis of Leucascandrolide A,"The formal total synthesis of leucascandrolide A has been achieved in 20 steps from a known epoxide with an overall yield of 11.5% following a recently developed strategy for the construction of trans-2,6-disubstituted-3,4-dihydropyrans and a Lewis acid catalyzed intramolecular Prins-cyclization of an aldehydic homoallylic alcohol to generate the tetrahydropyran ring with three stereogenic centers and macrocycle concomitantly.",10.1021/ol200223q,2011-03-09,0.6501010516310393
Synlett,The Intramolecular Diels-Alder Reaction with Furan-Diene: A Novel Route to (±)-Gibberellin A<sub>5</sub>,"All articles of this category A novel potential approach to 20-norgibberellins is described and exemplified with the total synthesis of (±)-gibberellin A 5 from methyl (1 S ,2 R , 5 S )-2-(2-furyl)-5-hydroxy-6-methylenebicyclo[3.2.1]octane-1-carboxylate. Key steps involve an intramolecular Diels-Alder reaction with the furan-diene moiety leading to a kaurenoid analogue and the subsequent ring contraction of the central 5-membered ring to yield the required carboxy-substituted cyclopentane moiety via a photochemical α-diazo ketone Wolff rearrangement.",10.1055/s-1991-20788,1991-01-01,0.650086805820029
Organic Letters,Collective Total Synthesis of Four <i>Ganoderma</i> Meroterpenoids Based on an Intramolecular Aldol Strategy,"meroterpenoids (lingzhiol, sinensilactam A, lingzhilactone B, and applanatumol I) has been accomplished from a known olefinic lactone in much shorter steps (4-8 steps) and markedly improved overall yields (15-27%) compared to previous syntheses. The key steps are highly regio- and diastereoselective intramolecular aldol reactions to prepare bicyclic lactone intermediates and a decarboxylative radical cyclization to install the unique tetracyclic ring system of lingzhiol.",10.1021/acs.orglett.4c04756,2025-02-25,0.6500573423438069
Organic Process Research & Development,Development of a Scalable Manufacturing Process for Alectinib with a Concise Preparation of the Indole-Containing Tetracyclic Core,"Alectinib (marketed as Alecensa) is an oral, highly potent ALK inhibitor for the treatment of ALK-positive, non–small-cell lung cancer (NSCLC). This paper describes the evolution from a medicinal chemistry synthetic process to a process enabling the scaled-up supply of a high-quality drug substance. A characteristic structural feature of alectinib is its indole-containing tetracyclic core, the construction of which was effectively achieved through intramolecular reductive cyclization and an intramolecular Friedel–Crafts reaction. Furthermore, the optimized synthetic route and conditions were designed to suppress the formation of impurities containing the same tetracyclic scaffold that are difficult to purge in downstream processes. The established manufacturing process could consistently produce alectinib on a multikilogram scale, typically with an overall yield of 29% and purity exceeding 99.9 area%.",10.1021/acs.oprd.4c00376,2024-10-22,0.6500470763735425
Synthesis,Phosphine-Catalyzed Tandem α-O-Addition and Transesterification of Oxgen Pronucleophiles on Arylpropiolates: A New Route to Dioxygenated Heterocyles,"A practical one step procedure for the synthesis of 1,4-dioxane-2-one and 1,4-benzodioxine-2-one derivatives is described.",10.1055/s-2007-965900,2007-01-22,0.650024109141856
Journal of Organic Chemistry,Total Synthesis of Isoroquefortine C,"A short and efficient total synthesis of isoroquefortine C, the 3,12-(Z)-isomer of roquefortine C, from L-tryptophan methyl ester hydrochloride and 4(5)-(hydroxy)methylimidazole hydrochloride is described.",10.1021/jo0106593,2001-10-26,0.6500227487599348
Tetrahedron,"A new route to 1,4-oxazepanes and 1,4-diazepanes from Garner aldehyde",,10.1016/j.tetlet.2010.01.035,2010-01-19,0.6500149770443383
Angewandte Chemie International Edition,Biomimetic Total Synthesis of (±)‐Merochlorin A,"Inspired: The proposed biosynthetic pathway toward the potent antibiotic meroterpenoid (±)-merochlorin A inspired its concise total synthesis. The key steps in the synthesis are a one-pot aromatization–alkylation reaction, followed by a biomimetic oxidative dearomatization of a highly functionalized naphthalene derivative, which forms two rings and four contiguous stereocenters in a single step.",10.1002/anie.201307200,2013-09-23,0.6500014379160567
Journal of the American Chemical Society,"Catalysis-Based and Protecting-Group-Free Total Syntheses of the Marine Oxylipins Hybridalactone and the Ecklonialactones A, B, and C","Concise and protecting-group-free total syntheses of the marine oxylipins hybridalactone (1) and three members of the ecklonialactone family (2-4) were developed. They deliver these targets in optically pure form in 14 or 13 steps, respectively, in the longest linear sequence; five of these steps are metal-catalyzed and four others are metal-mediated. The route to either 1 or 2-4 diverges from the common building block 22, which is accessible in 7 steps from 2[5H]furanone by recourse to a rhodium-catalyzed asymmetric 1,4-addition reaction controlled by the carvone-derived diene ligand 35 and a ring-closing alkene metathesis (RCM) catalyzed by the ruthenium indenylidene complex 17 as the key operations. Alternatively, 22 can be made in 10 steps from furfural via a diastereoselective three-component coupling process. The further elaboration of 22 into hybridalactone as the structurally most complex target with seven contiguous chiral centers was based upon a sequence of cyclopropanation followed by a vanadium-catalyzed epoxidation, both of which were directed by the same free hydroxy group at C15. The macrocyclic scaffold was annulated to the headgroup by means of a ring-closing alkyne metathesis reaction (RCAM). In response to the unusually high propensity of the oxirane of the targeted oxylipins for ring opening, this transformation had to be performed with complexes of the type [(Ar(3)SiO)(4)Mo≡CPh][K·OEt(2)] (43), which represent a new generation of exceedingly tolerant yet remarkably efficient catalysts. Their ancillary triarylsilanolate ligands temper the Lewis acidity of the molybdenum center but are not sufficiently nucleophilic to engage in the opening of the fragile epoxide ring. A final semireduction of the cycloalkyne formed in the RCAM step to the required (Z)-alkene completed the total synthesis of (-)-1. The fact that the route from the common fragment 22 to the ecklonialactones could follow a similar logic showcased the flexibility inherent to the chosen approach.",10.1021/ja204027a,2011-07-22,0.6499940039456784
Organic Process Research & Development,Alternate Synthesis of a β-3 Adrenergic Receptor Agonist,"Previously our group reported synthetic efforts used to synthesize kilogram quantities of the β-3 receptor agonist ( R )-(4-(2-(2-(6-aminopyridin-3-yl)-2-hydroxyethylamino)ethoxy)phenyl)acetic acid, 1 . Additional research was conducted to explore an alternate chiral route with a streamlined protecting group scheme. The alternate asymmetric process and synthetic rationale are described.",10.1021/op0499775,2004-05-28,0.6499734093161857
Organic Letters,"A Convergent Synthesis of (+)-Cryptophycin B, a Potent Antitumor Macrolide from <i>Nostoc</i> sp. Cyanobacteria","[structure--see text] An efficient and highly stereoselective synthesis of cryptophycin B (2), a potent cytotoxic agent, is described. The ester-derived titanium-enolate-mediated syn-aldol reaction was employed to generate the stereocenters C(5) and C(6). The route is convergent and provides a convenient access to the synthesis of structural variants of cryptophycin B as well as members of its family.",10.1021/ol000058i,2000-05-11,0.6499706116912757
Synthesis,Efficient Chiral Pool Synthesis of the C1-C6 Fragment of Epothilones,An efficient chiral pool synthesis of the C1-C6 fragment of epothilones starting from readily available(-)-pantolactone is described.,10.1055/s-2004-834936,2005-01-01,0.6499678088703185
Organic Process Research & Development,Development of a Large-Scale Route to an MCH<sub>1</sub> Receptor Antagonist: Investigation of a Staudinger Ketene–Imine Cycloaddition in Batch and Flow Mode,A practical large-scale route to an MCH 1 receptor antagonist is described. A Staudinger β-lactam synthesis of an imine and an in situ generated ketene was utilized as a key step for the preparation of a spiro-azetidine building block. The reaction was demonstrated in both batch and flow mode and a comparison of these techniques is described.,10.1021/acs.oprd.5b00319,2015-11-12,0.649961618014321
Organic Process Research & Development,Development of Adagrasib’s Commercial Manufacturing Route,"A commercial route to adagrasib ( 1 ) was developed to support clinical and commercial needs. Yield was improved to 32% over six chemical steps. A doubly regioselective S N Ar reduced consumption of a chiral intermediate, reaction optimization led to parts per million palladium catalysis, and a new method to deprotect Cbz-groups were developed to mitigate risk associated with benzyl iodide.",10.1021/acs.oprd.2c00386,2023-02-17,0.6499607387846398
Synthesis,Prins Cyclization: Novel Strategy towards the Diastereoselective Total Synthesis of (–)-Cryptocaryolone,"Abstract A highly diastereoselective total synthesis of TBDPS-protected (–)-cryptocaryolone has been achieved in 12 linear steps with an overall yield of 7.1%, following a recently developed Prins cyclization strategy for the construction of trans-2,6-disubstituted 3,4-dihydropyrans. Another key intermediate, i.e. syn-1,3-diol, was prepared by the Wacker oxidation followed by a hydroxyl-directed syn-reduction of the keto functionality. In this report, the versatility of Prins cyclization in the total synthesis of TBDPS-protected (–)-cryptocaryolone is demonstrated. The key steps involved in the approach are Prins cyclization for the construction of the trans-2,6-disubstituted dihydropyran, Wacker oxidation and a hydroxyl-directed syn-reduction reaction.",10.1055/a-2152-0671,2023-08-10,0.6499509298463736
Angewandte Chemie International Edition,"A Divergent Synthetic Route to the Vallesamidine and Schizozygine Alkaloids: Total Synthesis of (+)‐Vallesamidine and (+)‐14,15‐Dehydrostrempeliopine","The total synthesis of representative members of the schizozygine alkaloids, (+)-vallesamidine and (+)-14,15-dehydrostrempeliopine, were completed from a late-stage divergent intermediate. The synthesis took advantage of efficient nitro-group reactions with the A/B/C ring skeleton constructed concisely on a gram scale through an asymmetric Michael addition, nitro-Mannich/lactamisation, Tsuji-Trost allylation, and intramolecular C-N coupling reaction. Other key features of the synthesis are a novel [1,4] hydride transfer/Mannich-type cyclisation to build ring E and a diastereoselective ring-closing metathesis reaction to construct ring D. This approach gave access to a late-stage C14,C15 alkene divergent intermediate that could be simply transformed into (+)-vallesamidine, (+)-14,15-dehydrostrempeliopine, and potentially other schizozygine alkaloids and unnatural derivatives.",10.1002/anie.201910593,2019-09-20,0.6499258357696176
Angewandte Chemie International Edition,Total Synthesis of Pallamolides A−E,"Abstract We have achieved the first total synthesis of pallamolides A−E. Of these compounds, pallamolides B−E possess intriguing tetracyclic skeletons with novel intramolecular transesterifications. Key transformations include highly diastereoselective sequential Michael addition reactions to construct the bicyclo[2.2.2]octane core with the simultaneous generation of two quaternary carbon centers, a one‐pot SmI 2 ‐mediated intramolecular ketyl–enoate cyclization/ketone reduction to generate the key oxabicyclo[3.3.1]nonane moiety, and an acid‐mediated deprotection/oxa‐Michael addition/β‐hydroxy elimination cascade sequence to assemble the tetracyclic pallamolide skeleton. Kinetic resolution of ketone 14 through Corey–Bakshi–Shibata reduction enabled the asymmetric synthesis of pallamolides A−E.",10.1002/anie.202319127,2024-03-20,0.6499241944103935
Organic Letters,Enantioselective Synthesis of the Pyrroloquinoline Core of the Martinellines,"[equation--see text] The first enantioselective synthesis of the martinelline core (-)-3 is reported. The synthesis of (-)-3 from N-allyl-N-(benzyloxycarbonyl)-2-iodoaniline (12) proceeded in seven steps and 23% overall yield. In addition, the preparation of a carbocyclic model system is described.",10.1021/ol0057030,2000-04-20,0.6499194543866925
Journal of Organic Chemistry,Protecting Group-Free Total Synthesis of (−)-Boscartin H,"Herein, we report the first protecting group-free total synthesis of (-)-boscartin H, which features a 5-12-5-fused tricyclic structure. The key steps, which include a diastereoselective THF-ring-forming/aldol reaction sequence and ring-closing metathesis, afforded high stereoselectivity with (-)-boscartin H obtained in 3.6% overall yield using a 11-step long linear sequence. In addition, X-ray crystallography clearly confirmed the stereochemistry of boscartin H.",10.1021/acs.joc.4c00797,2024-05-31,0.6499182135018384
Organic Letters,Scalable Synthesis of (−)-Rasfonin Enabled by a Convergent Enantioselective α-Hydroxymethylation Strategy,"A scalable synthesis of the potent antitumor agent, (-)-rasfonin, has been achieved. The synthetic strategy features a highly convergent approach based on a single protocol construction of both major fragments via catalytic enantioselective α-hydroxymethylation of simple aliphatic aldehydes. The route described has been successful in the generation of gram quantities of the natural product and serves as the first synthetic strategy to provide sufficient material to continue studies related to its mechanism of action and potential as a cancer therapeutic.",10.1021/acs.orglett.8b02222,2018-08-03,0.6499128845179057
Tetrahedron,Synthesis of 5-deoxy-5-phospho-d-ribonohydroxamic acid: a new competitive and selective inhibitor of type B ribose-5-phosphate isomerase from Mycobacterium tuberculosis,,10.1016/j.tetlet.2005.03.151,2005-04-07,0.6498972945745127
Tetrahedron,Enantioselective syntheses of (+)-methyl nonactate and (−)-methyl 8-epi-nonactate via asymmetric cycloadditive route,,10.1016/s0040-4039(00)92241-x,1992-04-01,0.649893350641388
Synthesis,"1,4-Dioxamacrolides: Preparation and Sensory Properties","The synthesis of 3-methyl-1,4-dioxacylopentadecan-2-one (12c) and 3-methyl-1,4-dioxacylohexadecan-2-one (12d), two new musk odorants, is described starting from methyl 2-bromopropionic acid (6b) and allylic alcohol, respectively. The key step of the synthesis is the ring-closing olefin metathesis (RCM) to the unsaturated 1,4-dioxamacrolides. Insight into the structure-odor relationship (SOR) is provided by the synthesis of ten related unsubstituted or methyl substituted oxamacrolides. Finally, a four step enantioselective synthesis of both (3R)-(+)- and (3S)-(-)-3-methyl-1,4-dioxacyclopentadecan-2-one as well as (3R)-(+)- and (3S)-(-)-3-methyl-1,4-dioxacyclohexadecan-2-one reveals that mainly the (3R)-(+) enantiomers are responsible for the powerful musky odor characteristic. Their synthesis starts from ethyl (2S)-2-hydroxy­propanoate (14) or isobutyl (2R)-2-hydroxypropanoate (15) which were treated under acidic conditions with allyl trichloroacetimidate (16), followed by titanate mediated transesterification, ring-closing olefin metathesis and hydrogenation.",10.1055/s-2003-37345,2003-01-01,0.6498933063406702
Tetrahedron,LHMDS mediated tandem acylation–cyclization of 2-aminobenzenecarbonitriles with 2-benzymidazol-2-yl acetates: a short and efficient route to the synthesis of 4-amino-3-benzimidazol-2-ylhydroquinolin-2-ones,,10.1016/j.tetlet.2005.11.113,2005-12-10,0.6498853005089087
Journal of the American Chemical Society,Total Synthesis of (−)-Spirotryprostatin B:  Synthesis and Related Studies,"The total synthesis of spirotryprostatin B, a cytostatic spiro[pyrrolidine-3,3'-oxindole] alkaloid, is described. The key step of the synthetic approach consists of the application of the MgI2-mediated ring-expansion reaction of a spiro[cyclopropane-1,3'-oxindole] with an aldimine, leading to rapid assembly of the spirotryprostatin core. The route documents the installation of the prenyl side chain by Julia-Kocieński olefination of a key aldehyde precursor, a transformation that ultimately allows for facile synthesis of analogues and facilitates structure-activity relationships studies.",10.1021/ja0518880,2005-07-26,0.6498681344775051
Synlett,Synthesis of a Mumbaistatin Analogue through Cross-Coupling,"Studies on the total synthesis of mumbaistatin, the ­strongest natural inhibitor of G6P-T1, have culminated in the synthesis of a 4′′,8-dideoxy analogue. Key steps include a Diels-Alder reaction for the construction of the functionalized anthraquinone, a palladium-catalyzed Stille coupling to generate a tetra-ortho-sub­stituted diarylmethane, and a titanium-mediated alkynylation of an aldehyde to complete the carbon skeleton of mumbaistatin. Radical bromination of the methylene bridge afforded a lactone, which ­resembles the target structure in its cyclized form.",10.1055/s-2007-986652,2007-09-21,0.6498565495300017
Journal of Organic Chemistry,Total Synthesis of (−)-Luminacin D,"A second-generation synthesis of (-)-luminacin D based on an early stage introduction of the trisubstituted epoxide group is reported, allowing access to the natural product in an improved yield and a reduced number of steps (5.4%, 17 steps vs 2.6%, 19 steps). A full account of the optimization work is provided, with the reversal of stereoselection in the formation of the C4 alcohol in equally excellent diastereoselectivity as the key improvement.",10.1021/acs.joc.6b00489,2016-04-07,0.6498523679823859
Synlett,"Efficient Synthesis of (3<i>R</i>,5<i>S</i>)-3,5,6-Trihydroxyhexanoic Acid Derivative as a Chiral Side Chain of Statins","Efficient synthesis of tert-butyl [(3R,5S)-6-hydroxy­methyl-2,2-dimethyl-1,3-dioxan-4-yl]acetate (1) has been accomplished. Unprecedented hydration of 3 in the presence of lithium chloride provided 4a,b, the primary hydroxyl group of which reacted with pivaloyl- and 1-naphthoyl chloride, respectively, in pyridine to give 7a or 7d in improved selectivity. Diastereoselective reduction of 7a and protection-deprotection sequence provided 1.",10.1055/s-2008-1078428,2008-06-01,0.649841549391443
Organic Letters,"Streamlined Access to Peptidoglycan Biosynthesis Terminator GlcNAc-1,6-anhydro-MurNAc","GlcNAc-1,6-anhydro-MurNAc is a key peptidoglycan elongation terminator of biological and medicinal importance. Herein, we present a concise approach to this molecule in 12 steps with an overall 25% yield using d-glucosamine as the sole starting material. Our synthesis features the formation of a 1,6-anhydro-MurNAc building block by an intramolecular glycosylation and the selective conversion of the phthalimido group of the MurNPhth moiety, paving the way for antibiotics with a new killing mechanism by targeting bacterial transglycosylase.",10.1021/acs.orglett.4c04620,2025-01-06,0.649822998758058
Organic Process Research & Development,Development of an Expedient Process for the Multi-Kilogram Synthesis of Chk1 Inhibitor GDC-0425,"A process leading to the multikilogram GMP synthesis of Chk1 inhibitor GDC-0425 ( 1 ) was developed. Highlights of the synthesis include protection of the pyrrole ring of a 1,7-diazacarbazole as propyl ethyl ether, an efficient Pd catalyzed cyanation of an aryl chloride, aryl ether formation by SNAr fluoride displacement, and development of a controlled crystallization providing the API with the required polymorphic form. The process delivered high-quality GDC-0425 with low levels of impurities and residual metals in five steps and 31% overall yield.",10.1021/acs.oprd.5b00105,2015-05-13,0.6498201148606402
Journal of Organic Chemistry,"New Convergent Synthesis of 1α,25-Dihydroxyvitamin D<sub>3</sub> and Its Analogues by Suzuki−Miyaura Coupling between A-Ring and C,D-Ring Parts","A new convergent method for the synthesis of 1alpha,25-dihydroxyvitamin D(3) and its analogues has been developed that involves efficient preparation of the A-ring part 1a, (Z)-(3S,5R)-1-bromomethylene-3,5-bis(tert-butyldimethylsilyloxy)-2-methylenecyclohexane, starting from epichlorohydrin (4) and its Suzuki-Miyaura coupling reaction with the C,D-ring part 12. Thus, (R)-4 was converted to (3S,5R)-5-(tert-butyldimethylsilyloxy)-8-(trimethylsilyl)-oct-1-en-7-yn-3-ol (3a) through a ten-step reaction sequence in 49% overall yield. Compound 3a thus obtained was treated with a Ti(O-i-Pr)(4)/2 i-PrMgCl reagent and then with NBS to afford (Z)-(1S,2S,5R)-2-bromomethyl-3-[bromo(trimethylsilyl)methylene]-5-(tert-butyldimethylsilyloxy)cyclohexanol (10a) in 51% yield, from which 1a was obtained in 87% yield by sequential treatment with TBSCl/imidazole, DBU, and Cs(2)CO(3). The resulting A-ring intermediate 1a was reacted with alkenylboronate 12 in the presence of a PdCl(2)(dppf) catalyst to furnish 1alpha,25-dihydroxyvitamin D(3) in 82% yield after protodesilylation. Similarly, all of the other three possible stereoisomers of A-ring parts 1b, 1c, and 1d were prepared, from which 1-epi-, 3-epi-, and 1,3-di-epi-1alpha,25-dihydroxyvitamin D(3) were synthesized by coupling with 12 in excellent yield, respectively. Starting from 1a and 1c, des-C,D-1alpha,25-dihydroxyvitamin D(3) analogues, retiferol 13 and its 3-epi derivative, were also prepared, respectively.",10.1021/jo0353435,2003-11-19,0.649818443502777
Journal of Organic Chemistry,"Enantioselective synthesis and determination of the configuration of stenusine, the spreading agent of the beetle Stenus comma","The enantioselective total synthesis of two of the four possible stereoisomers of stenusine (1), the spreading agent of the beetle Stenus comma, is described. The silyl ether-substituted aldehyde SAMP hydrazone 2 was alkylated with (S)-1-bromo-2-methylbutane (3) yielding the hydrazone 4 in high diastereomeric purity (de >95 %). By several steps including the reduction of the hydrazone functionality and the cleavage of the N-N bond of the intermediates, 4 was converted into the BOC-protected amino alcohol 6. Subsequent cyclization of 6 afforded the (S,S) diastereomer of stenusine with 96.6 % de, >99.9 % ee, and in 11.3 % overall yield. Repetition of this synthesis using the aldehyde RAMP hydrazone (R)-2 as the starting material produced (SR)-1 with 95.0 % de, >99 % ee, and in 8.2 % overall yield. The synthetic samples of 1 were employed to investigate the stereochemistry of natural stenusine by means of GC analysis on both a chiral and an achiral, stationary phase. As a result of these studies natural stenusine was found to be a mixture of all four stereoisomers in a ratio of (S,S)/(SR)/(RR)/(R:S) = 43:40:13:4.",10.1021/jo00070a024,1993-08-01,0.6498096451016953
Tetrahedron,A new and efficient one-pot synthesis of indoles,,10.1016/j.tetlet.2007.12.015,2007-12-10,0.6497928286302961
Journal of the American Chemical Society,Total Synthesis of the <i>Lycopodium</i> Alkaloid (+)-Serratezomine A,"The first total synthesis of (+)-serratezomine A is described. Key aspects of the synthesis include (a) the first deployment of free-radical-mediated vinyl amination (an intramolecular alkyne aminostannation) in a complex target synthesis, (b) the use of a beta-stannyl enamine as the lynchpin for convergent assembly of the natural product backbone, (c) the use of an oxidative allylation promoted by cerium(IV) (CAN) to establish the all-carbon quaternary chiral center with the proper configuration, and (d) an intramolecular substitution reaction to form the sensitive bridging lactone. Overall, 15 steps (longest linear sequence) are required to prepare the natural product from a commercially available aldehyde, and assembly of the contiguous array of six stereocenters is accomplished with high stereocontrol.",10.1021/ja900536d,2009-02-24,0.6497726492009808
Synthesis,Synthetic Studies towards NG-121: Diastereoselective Synthesis of NG-121 Methyl Ether,"Starting from unsymmetrically O-protected methyl 4-bromo-3,5-dihydroxybenzoate, a facile synthesis of the methyl ether of bioactive natural product NG-121 was accomplished in very good overall yield. The key steps were: Stille coupling reaction of the farnesyl unit with the electron-rich phenolic segment; hydroxy-directed selective epoxidation of the farnesyl chain along with concomitant phenol-driven intramolecular regio- and diastereoselective ring closure to the corresponding hydroxybenzopyran; and regioselective formylation followed by in situ reductive lactonization.",10.1055/s-0032-1317544,2012-10-31,0.6497722109759543
Angewandte Chemie International Edition,Total Synthesis of (−)‐Ophiodilactone A and (−)‐Ophiodilactone B,"The first asymmetric total synthesis of (-)-ophiodilactone A and (-)-ophiodilactone B, isolated from the ophiuroid (Ophiocoma scolopendrina), is reported. The key features of the synthesis include the highly stereocontrolled construction of the structurally congested γ-lactone/δ-lactone skeleton through an asymmetric epoxidation, diastereoselective iodolactonization, and intramolecular epoxide-opening with a carboxylic acid, and biomimetic radical cyclization of ophiodilactone A to ophiodilactone B.",10.1002/anie.201307835,2013-12-11,0.6497573624105231
Organic Process Research & Development,Synthesis of MDM2-p53 Inhibitor BI-0282 via a Dipolar Cycloaddition and Late-Stage Davis–Beirut Reaction,"Herein, we report the structure and synthesis of the potent MDM2-p53 inhibitor BI-0282. The complex spirooxindole scaffold bearing four stereocenters embedded in a rigid polycyclic ring-system was effectively prepared on a multi-gram scale in only five synthesis steps employing a three-component 1,3-dipolar cycloaddition and a late-stage Davis-Beirut reaction as key steps.",10.1021/acs.oprd.2c00192,2022-07-07,0.6497320390324343
Synthesis,Total Synthesis of the 5-HT3 Receptor Antagonist Palonosetron,"All articles of this category A short and efficient synthetic route to the 5-HT 3 receptor antagonists 1 and 2 (palonosetron) was developed. The novel adjustment of the oxidation states at the necessary centers of imide 7 was accomplished by hydrogenation, selective sodium borohydride reduction, and dehydration to yield 1 . The sodium borohydride reduction of imide 8 was selective for the C-3 carbonyl versus the C-1 carbonyl next to the aromatic ring to give the hydroxy compound 9 . It was essential to keep the sodium borohydride reduction free of oxygen, or diols 10a and 10b were formed as significant byproducts. palonosetron - imide - selective reduction - 5-HT 3 receptor antagonist",10.1055/s-1996-4315,1996-07-01,0.6497250667957962
Tetrahedron,An efficient synthesis of the orally-active GpIIb/IIIa antagonist FR184764,,10.1016/j.tetlet.2004.01.157,2004-03-01,0.6497249167807131
Journal of Organic Chemistry,"New Syntheses of the C,D-Ring Pyrromethenones of Phytochrome and Phycocyanin","Pyrromethenone 7, the C,D-ring segment of phytochrome (Pr, 4), has been prepared in an efficient fashion employing three new strategies. Each of these has potential advantages for the synthesis of labeled material. Our first approach is related to the Gossauer synthesis, with the difference that strong alkali is avoided in the condensation of the C- and D-ring components 8 and 17. The key silyloxypyrrole 17 was readily prepared on multigram scales beginning with inexpensive butyrolactone (10). A second synthesis began with 2-acetylbutyrolactone (41). The key steps involved conversion of 41 to the Z-enoltriflate 42, followed by Pd(0)-catalyzed coupling with trimethylsilylacetylene, p-chlorophenylselenide ring opening, and finally, amidation to afford the ring-D synthon 45 having the proper geometry and oxidation state for conversion to 7. Sonogashira coupling of 45 with the iodopyrrole 22, followed by oxidative elimination, and F(-)-induced 5-exo-dig cyclization of the resultant pyrroloalkyne 47, then completed the synthesis. In similar fashion, we have also prepared pyrromethenone 6, the C,D-ring segment of phycocyanin (2).",10.1021/jo005531k,2000-11-10,0.6497196915495105
Chemical Science,"Novel synthetic route for (parent) phosphetanes, phospholanes, phosphinanes and phosphepanes","A novel synthetic route for (parent) phosphorus-containing cycloalkanes such as phosphetanes, phospholanes, 5 phosphinanes and phosphepanes and their organo-substituted derivatives is reported. For the first time the parent phospholane was synthesised.",10.1039/d3sc00580a,2023-01-01,0.6497121610685191
Synlett,"Enantioselective Synthesis of (+)-l-733,060 and (+)-CP-99,994: Application of an Ireland-Claisen Rearrangement/Michael Addition Domino Sequence","An efficient asymmetric synthesis of (+)-l-733,060, (-)-(2S,3R)-1 and (+)-CP-99,994, starting from a Baylis-Hillman adduct, is described. The key steps include a novel domino reaction: stereoselective Ireland-Claisen rearrangement, asymmetric Michael addition, and piperidone ring formation through a one-pot reaction hydrogenolysis/lactamization and a stereoselective inversion of a hydroxy group.",10.1055/s-0029-1219200,2010-01-19,0.6497085760428443
Synlett,"Intramolecular [3 + 2]-Hetero-Annulation of Allylsilanes with 1,3-Cyclohexanediones and its Application in the Synthesis of Hexacyclic Hopane Triterpenes","All articles of this category In this letter we describe the intramolecular [3 + 2]-hetero-annulation of allylsilanes with 1,3-cyclohexanediones followed by sila-Wagner-Meerwein shift. The new synthesis of the cyclization precursors offers the advantage to vary the silyl terminator at the end of the synthetic sequence. The Lewis acid-mediated cyclization was optimized for the synthesis of the D-E-F-subunit of hexacyclic hopane triterpenes. The AB-fragment of these terpenes was synthesized in one step via regioselective ring opening of commercially available (-)-ambroxide. cyclizations - Lewis acids - silicon - terpenoids - total synthesis",10.1055/s-2000-7132,2000-01-01,0.6496901397354762
Tetrahedron,Synthesis of sesbanimide: An approach for the synthesis of ring C,,10.1016/s0040-4039(00)84158-1,1986-01-01,0.6496892679491332
European Journal of Organic Chemistry,Synthesis of Elemane Bis-Lactones from Santonin – Synthesis of the Reported Structure ofseco-Isoerivanin Pseudo Acid and Formal Synthesis of (+)-8-Deoxyvernolepin,The synthesis of the reported structure for seco-isoerivanin pseudo acid (1) and of an elemane bis-lactone 5 from santonin (4) through a common vinylic precursor 12 is described. Compound 5 is a known intermediate in a previous synthesis of the antitumor compound (+)-8-deoxyvernolepin (3). The vinyl group of 12 underwent a regio- and diastereoselective anti addition of an external electrophile and an intramolecular condensation to yield either the selenolactone 13 or the hydroxylactone 17. The lactones 13 and 17 served as key intermediates in the total synthesis of 1 and 5 respectively. A revision of the structure of seco-isoerivanin pseudo acid to the C-10 epimer is suggested on the basis of comparison between the spectral data of the natural and synthetic products.,10.1002/1099-0690(200006)2000:11<2145::aid-ejoc2145>3.0.co;2-n,2000-06-01,0.649635001117748
Journal of Organic Chemistry,Total Synthesis of (±)-Brazilin Using [4 + 1] Palladium-Catalyzed Carbenylative Annulation,"Palladium-catalyzed carbene insertion was utilized in a formal synthesis of (±)-picropodophyllone and a total synthesis of (±)-brazilin. All prior syntheses of brazilin have involved a Friedel–Crafts alkylation in the key carbon–carbon bond forming events. The palladium-catalyzed [4 + 1] reaction generates a 1-arylindane with all of the functionalities needed for formation of the indano[2,1- c ]chroman ring system of brazilin. The synthesis of (±)-brazilin was achieved in 11 steps (longest linear sequence) with an overall 11% yield.",10.1021/acs.joc.9b02343,2019-10-22,0.6496175003329476
Angewandte Chemie International Edition,Highly Efficient Stereocontrolled Total Synthesis of the Polyfunctional Carotenoid Peridinin,"The convergent, highly stereoselective synthesis of the nor carotenoid peridinin (1) is based on the following key steps: a) a Sharpless asymmetric epoxidation, b) reaction with a silylfuran-Wittig reagent and oxidation with 1O2, c) a Pd-catalyzed three-step one-pot procedure for the formation of the ylidene butenolide segment), and d) a modified Julia olefination. This provides a new method for the synthesis of carotenoids.",10.1002/1521-3773(20020315)41:6<1023::aid-anie1023>3.0.co;2-a,2002-03-15,0.6495926457500499
Tetrahedron,A new approach to asymmetric synthesis of Stork's prostaglandin intermediate,,10.1016/s0040-4039(00)73815-9,1993-09-01,0.6495558077849448
Organic Process Research & Development,Development of Two Scalable Syntheses of 4-Amino-5-aminomethyl-2-methylpyrimidine: Key Intermediate for Vitamin B<sub>1</sub>,"Two scalable processes for the synthesis of 4-amino-5-aminomethyl-2-methylpyrimidine ( 2 ) are described. In the first approach, the less expensive 2-cyanoacetamide was reacted with Vilsmeier reagent to afford enamine 18, followed by the condensation with acetamidine to produce the 4-amino-2-methylpyrimidine-5-carbonitrile ( 6 ); subsequent hydrogenation gave 2 in 65% overall yield. In the second approach, malononitrile was treated with the ionic salt 21, prepared in situ from DMF and dimethyl sulfate, to give 18, which, without isolation was reacted with acetamidine hydrochloride to afford the common intermediate 6 . Overall yield of this approach was 70%. Both methods are performed in a convenient manner suitable for industrial use.",10.1021/op2002003,2011-11-01,0.6495543333071626
Journal of the American Chemical Society,"A Practical, Component-Based Synthetic Route to Methylthiolincosamine Permitting Facile Northern-Half Diversification of Lincosamide Antibiotics","The development of a flexible, component-based synthetic route to the amino sugar fragment of the lincosamide antibiotics is described. This route hinges on the application and extension of nitroaldol chemistry to forge strategic bonds within complex amino sugar targets and employs a glycal epoxide as a versatile glycosyl donor for the installation of anomeric groups. Through building-block exchange and late-stage functionalization, this route affords access to a host of rationally designed lincosamides otherwise inaccessible by semisynthesis and underpins a platform for the discovery of new lincosamide antibiotics.",10.1021/jacs.1c03536,2021-04-30,0.6495077845764814
Tetrahedron,A new aromatization of ring-A of steroids. Synthesis of estrone,,10.1016/0040-4039(88)80021-2,1988-01-01,0.649496223004572
Tetrahedron,A new synthesis of the vernolepin a-ring,,10.1016/s0040-4039(01)82561-2,1974-01-01,0.649496223004572
Tetrahedron,A new indazole ring synthesis,,10.1016/s0040-4039(01)98480-1,1970-01-01,0.649496223004572
Organic Letters,"Asymmetric Synthesis of <i>cis</i>-2,5-Disubstituted Pyrrolidine, the Core Scaffold of β<sub>3</sub>-AR Agonists","A practical, enantioselective synthesis of cis-2,5-disubstituted pyrrolidine is described. Application of an enzymatic DKR reduction of a keto ester, which is easily accessed through a novel intramolecular N→C benzoyl migration, yields syn-1,2-amino alcohol in >99% ee and >99:1 dr. Subsequent hydrogenation of cyclic imine affords the cis-pyrrolidine in high diastereoselectivity. By integrating biotechnology into organic synthesis and isolating only three intermediates over 11 steps, the core scaffold of β3-AR agonists is synthesized in 38% overall yield.",10.1021/ol400252p,2013-03-01,0.6494725383213742
Tetrahedron,Novel synthesis of Abaloparatide: Advancing osteoporosis treatment in postmenopausal women,,10.1016/j.tetlet.2024.155228,2024-07-30,0.6494709130459644
Organic Letters,<i>De Novo</i> Diastereoselective Synthesis of 1-Hydroxyl Allogibberic Methyl Ester <i>en Route</i> to Diverse Bioactive Molecules,"The first de novo synthesis of 1-hydroxyl allogibberic methyl ester, en route to pharbinilic acid and other bioactive molecules, is accomplished in diastereoselective manner. Key reactions of the synthesis include a Pd-catalyzed Suzuki–Miyaura cross-coupling reaction, a Lewis acid-catalyzed reductive Prins cyclization reaction, and a SmI 2 -mediated transannular pinacol coupling reaction. The synthesis provides a new avenue to access diverse relevant bioactive molecules.",10.1021/acs.orglett.2c02422,2022-08-26,0.64946341076865
Tetrahedron,"A new improved method for the synthesis of 2,4-diarylpyrimidines starting from 2,2,2-trichloroethylideneacetophenones",,10.1016/j.tetlet.2013.07.075,2013-07-17,0.649446922408371
Journal of Organic Chemistry,"Pyridinium Salt Photochemistry in a Concise Route for Synthesis of the Trehazolin Aminocyclitol, Trehazolamine","[reaction: see text] A strategy for the concise synthesis of trehazolamine, the aminocyclitol core of the potent trehalase inhibitor trehazolin, has been developed. The methodology takes advantage of photocyclization reaction of 1-methoxyethoxymethyl-3-pivaloxymethylpyridinium perchlorate to generate a bicyclic-aziridine intermediate, which is transformed under aziridine ring opening conditions to the key intermediate, 3,5-diacetoxy-3-pivaloxymethyl-4-(N-acetylamino)cyclopentene. In addition, the strategy is used in an enantio-divergent sequence for preparation of the natural (+)-trehazolamine and its unnatural (-)-enantiomer. In this route, the chiral auxiliary containing 1-(tetracetyl-alpha-D-glucosyl)-3-pivaloxymethylpyridinium perchlorate undergoes photocyclization to generate separable, diastereomeric bicyclic-aziridines, which are then independently transformed to enantiomeric 3,5-diacetoxy-3-pivaloxymethyl-4-(N-acetylamino)cyclopentenes.",10.1021/jo050589q,2005-05-26,0.6494277829382545
Journal of Organic Chemistry,Total Synthesis of Resorcinol Amide Hsp90 Inhibitor AT13387,"The synthesis of C-5-substituted resorcinol amide AT13387, a known Hsp90 inhibitor currently in clinical trials, is reported without the use of phenolic protection in an overall yield of 13.4%. Biomimetic aromatization and Suzuki-Miyaura cross coupling approach were employed to synthesize the resorcinol and iso-indoline units, respectively, which were efficiently coupled using Grignard-mediated amidation.",10.1021/jo302406w,2012-11-27,0.6494159803610715
Synthesis,"Formal Synthesis of Bioactive Indole Alkaloids Eburnamonine, Eburnaminol, and Vindeburnol","Starting from (±)-3-acetoxyglutarimide, diastereoselective formal synthesis of indole alkaloids (±)-eburnamonine, (±)-eburnaminol, and (±)-vindeburnol have been demonstrated via a common intermediate (±)-1-hydroxy-12-tosyl-2,3,6,7,12,12b-hexahydroindolo[2,3- a ]quinolizin-4(1 H )-one in very good overall yields. The acetoxy group from (±)-3-acetoxyglutarimide was first used to induce the diastereoselectivity and also as a latent source of ketone carbonyl group. The ste­reo­selective eliminations, reductions, and intramolecular cyclizations were the involved key steps.",10.1055/s-0036-1588386,2017-01-13,0.6494117806782054
Journal of Organic Chemistry,Preparation of Carbocyclic <i>S</i>-Adenosylazamethionine Accompanied by a Practical Synthesis of (−)-Aristeromycin.,Preparation of Carbocyclic S-Adenosylazamethionine Accompanied by a Practical Synthesis of (-)-,10.1021/jo051856v,2005-10-18,0.6494095732303035
Journal of Organic Chemistry,First Synthesis of Totally Orthogonal Protected α-(Trifluoromethyl)- and α-(Difluoromethyl)arginines,The first synthesis of a series of totally orthogonal protected racemic alpha-(trifluoromethyl)- and alpha-(difluoromethyl)arginines is described. The key steps of the synthesis are the mild guanidinylation procedure and the selective hydrogenation of a CC triple bond in the presence of a Cbz-group.,10.1021/jo0009043,2000-12-13,0.6494090751045966
Journal of the American Chemical Society,"Total Synthesis of Lobatoside E, A Potent Antitumor Cyclic Triterpene Saponin","Lobatoside E, a novel and complex cyclic triterpene saponin showing potent antitumor activities, has been synthesized for the first time, employing a highly modular approach. The synthesis, starting with oleanolic acid, D-glucose, D-galactose, L-arabinose, and L-rhamnose, requires a total of 73 steps, with the longest linear sequence of 31 steps and in 1.2% overall yield.",10.1021/ja801669r,2008-04-12,0.6493975345760394
Synlett,"Diastereo- and Enantioselective Synthesis of (-)-Oudemansin A via [2,3]-Wittig Rearrangement of Crotyloxyacetaldehyde-SAEP-Hydrazone","All articles of this category The total synthesis of (-)-oudemansin A ( 1 ) was accomplished in a ten-step sequence with good overall yield (20 %) and excellent diastereo- and enantiomeric excesses ( de, ee ≥ 98 %). Key step of the synthesis is the asymmetric [2,3]-Wittig rearrangement of crotyloxyacetaldehyde-SAEP-hydrazone [( S )- 6 ]. oudemansin A - [2,3]-Wittig rearrangement - magnesium monoperoxyphthalate - chiral hydrazone - asymmetric synthesis",10.1055/s-1995-5087,1995-08-01,0.6493755637500301
Organic Letters,"Synthesis of (<i>S</i>)-3-Amino-4-(difluoromethylenyl)-cyclopent-1-ene-1-carboxylic Acid (OV329), a Potent Inactivator of γ-Aminobutyric Acid Aminotransferase","( S)-3-Amino-4-(difluoromethylenyl)cyclopent-1-ene-1-carboxylic acid (OV329, 1) is being developed for the treatment of epilepsy and addiction. The previous 14-step synthesis of OV329 was low yielding, involved an unselective α-elimination to form the cyclopentene, required the use of tert-butyllithium, and produced toxic selenium byproducts in the penultimate step. A new synthesis, which avoids the aforementioned issues, was carried out on large scale, reducing the step count from 14 to 9 steps and increasing the overall yield from 3.7% to 8.1%.",10.1021/acs.orglett.8b01872,2018-07-16,0.6493680935543479
Organic Letters,Total Synthesis of Tambromycin Enabled by Indole C–H Functionalization,"The total synthesis of tambromycin (1), a recently isolated tetrapeptide, is reported. This unusual natural product possesses a highly modified tryptophan-derived indole fragment fused to an α-methylserine-derived oxazoline ring, and a unique noncanonical amino acid residue named tambroline (11). A convergent synthesis of tambromycin was achieved by a 13-step route that leveraged recent developments in the field of C-H functionalization to prepare the complex indole fragment, as well as an efficient synthesis of tambroline that featured a diastereoselective amination of homoproline.",10.1021/acs.orglett.8b00700,2018-03-27,0.6493675528024843
Journal of Organic Chemistry,De Novo Asymmetric Synthesis of Anamarine and Its Analogues,[reaction: see text] The enantioselective synthesis of anamarine has been achieved in 21 steps. The route relies on enantio- and regioselective Sharpless dihydroxylation of dienoate ester and zinc borohydride reduction to establish the C-8-C-11 stereochemistry. A diastereoselective Leighton allylation established the desired C-5 stereochemistry. The route has also been used to prepare two diastereoisomers of anamarine in 14 steps.,10.1021/jo051681p,2005-10-21,0.6493490891873086
Journal of Organic Chemistry,"Total Synthesis of (−)-Canadine, (−)-Rotundine, (−)-Sinactine, and (−)-Xylopinine Using a Last-Step Enantioselective Ir-Catalyzed Hydrogenation","A concise asymmetric total synthesis of a group of tetrahydroprotoberberine alkaloids, (-)-canadine, (-)-rotundine, (-)-sinactine, and (-)-xylopinine, has been accomplished in three steps from the commercially available corresponding disubstituted phenylethylamine and disubstituted benzaldehyde. Our synthesis toward these four alkaloids took advantage of the following strategy: in the first step, we achieved an efficient and sustainable synthesis of secondary amine hydrochlorides via a fully continuous flow; in the second step, we developed a Pictet-Spengler reaction/Friedel-Crafts hydroxyalkylation/dehydration cascade for the construction of the dihydroprotoberberine core structure (ABCD-ring); and in the last step, Ir-catalyzed enantioselective hydrogenation was employed for the introduction of the desired stereochemistry at the C-14 position in the tetrahydroprotoberberine alkaloids. This work significantly expedites the asymmetric synthesis of the entire tetrahydroprotoberberine alkaloid family as well as a more diverse set of structurally related non-natural analogues.",10.1021/acs.joc.1c00602,2021-06-02,0.6493486255904719
Tetrahedron,A new synthetic strategy for the synthesis of bioactive stilbene dimers. A direct synthesis of amurensin H,,10.1016/j.tetlet.2009.10.040,2009-10-15,0.6493377168680464
European Journal of Organic Chemistry,"Total Synthesis of (+)‐Strongylin A, a Rearranged Sesquiterpenoid Hydroquinone from a Marine Sponge","Abstract A biologically attractive and structurally unique marine natural product, (+)‐strongylin A ( 1 ), was synthesized for the first time by starting from a known trans ‐decalone derivative (19 % overall yield in 11 steps). The synthetic method involved the following key steps: (i) stereocontrolled hydrogenation of an exo ‐olefinic decalin to install the C8 stereogenic centre present in the required decalin segment; (ii) coupling of the decalin segment with an aromatic moiety to assemble the desired carbon skeleton; and (iii) sequential BF 3 · Et 2 O‐induced dehydroxylation/rearrangement/cyclization of a decalin tertiary alcohol to directly produce target compound 1 . This total synthesis has established the absolute configuration of the natural product.",10.1002/ejoc.201300438,2013-06-13,0.6493372812159637
Journal of Organic Chemistry,Asymmetric Total Synthesis and Structure Elucidation of Huperzine H,"A first asymmetric total synthesis of huperzine H has been achieved in a 12% overall yield from commercially available (+)-pulegone. The key steps of this synthesis include a highly diastereoselective Mukaiyama–Michael addition reaction of a pyrrole bearing a silyl enol ether and an intramolecular S N 2 cyclization reaction with iodinated pyrrole acting as an effective nucleophile for the formation of the nine-membered ring. As a result, the relative and absolute stereochemistry of huperzine H is established.",10.1021/acs.joc.1c02672,2022-01-18,0.649322084408402
Organic Letters,Total Synthesis of (−)-Callystatin A,"An effective total synthesis of (-)-callystatin A (1), member of the leptomycin family of antibiotics, has been achieved. The synthesis features Evans extended aldol methodology to construct the northern polypropionate subunit and two separate Julia olefinations to assemble the conjugated dienes. The total synthesis proceeded in 2.3% overall yield with the longest linear sequence of 15 steps.",10.1021/ol0158922,2001-04-17,0.6493014454629374
Organic Letters,The Imidato-Alkenyllithium Route for the Synthesis of the Isoquinocycline-Pyrrolopyrrole Substructure,"A convergent and effective synthesis of the pyrrolopyrrole substructure (CDEFG) of the isoquinocyclines is reported. A key step is a tin-lithium exchange of an imidato-alkenyltin compound (a ring G equivalent) and the subsequent acylation with a lactone. The resulting acetal is used successfully for the ring F closure to the pyrrolopyrrole. The sole formation of the isoquinocycline N,O-acetal epimer is in accordance with the proposed mechanism for the isomerization of quinocyclines to isoquinocyclines.",10.1021/ol200085g,2011-02-21,0.6493010773602356
Synthesis,"1H-1,3-Benzazaphospholes: The Organometallic Route and a New Three-Step Synthesis with Reductive Ring Closure","All articles of this category Primary and N -secondary 2-phosphanylanilines were synthesized via metallation of 2-bromoanilines, coupling with ClP(NMe 2 ) 2 , alcoholysis and reduction with LiAlH 4 , and subsequently reacted with formimidoester hydrochloride to give 1,3-benzazaphospholes. For 1 H -1,3-benzazaphospholes, a shorter alternative three-step synthesis was developed, based on N -acylation of 2-bromoaniline, NiCl 2 -catalyzed arylation of triethyl phosphite and a new reductive cyclization of amidophosphonic acid este with excess LiAlH 4 . C , N -dilithium reagent - phosphanylaniline - amidoarylphosphonate - reductive cyclization - 1,3-benzazaphosphole",10.1055/s-1999-3394,1999-02-01,0.6492807556572289
Angewandte Chemie International Edition,"Total Synthesis of Caprazol, a Core Structure of the Caprazamycin Antituberculosis Antibiotics","TB and anti-TB: Two key steps in the synthesis of caprazol (1), a core structure of the antituberculosis antibiotics, are the introduction of an aminoribose moiety by β-selective ribosylation without the use of neighboring-group participation and the construction of the diazepanone moiety.",10.1002/anie.200462439,2005-02-18,0.6492738583410301
Tetrahedron,A facile total synthesis of (±)-α-cuparenone employing diallylation and RCM as key steps,,10.1016/j.tetlet.2006.12.023,2007-01-05,0.6492674468240955
Synthesis,Synthesis of Potent CERT Inhibitor HPA-12 Featuring a Tandem Corey-Link and Intramolecular Nucleophilic Acyl Substitution Reaction,"A novel preparation of the potent CERT protein inhibitor (1 R ,3 S )-HPA-12 is described. The synthesis is accomplished in five steps from ( S )-Wynberg lactone and features a diastereoselective tandem Corey–Link and intramolecular nucleophilic acyl substitution reaction in a key step.",10.1055/s-0033-1338495,2013-06-06,0.649242631424483
Tetrahedron,An unexpected route for the synthesis of a new spiroheterocyclic system from ninhydrin,,10.1016/j.tetlet.2015.07.081,2015-08-01,0.6492274117326057
Organic Process Research & Development,Development of Versatile Routes for the Preparation of an Intermediate to Immuno-Oncology Agonist BMS-986299,"The development and optimization of two efficient and convenient routes for the construction of synthetic equivalents of 2-chloro-5-(1-(tetrahydro-2 H -pyran-2-yl)-1 H -pyrazol-5-yl)aniline, a key intermediate to immuno-oncology agonist ( BMS-986299 ), is described. The developed routes started from commercial available reagents into the desired pyrazole scaffolds smoothly with different substituents such as THP-, Bn -, and PMB- group tolerance. Finally, to further demonstrate the practicability, a large-scale process (10–30 g on a laboratory scale) was obtained through a simple crystallization or filtration without any column chromatography needed and may be suitable for the scalable production of the key intermediate for industrial applications.",10.1021/acs.oprd.3c00032,2023-04-26,0.6492249303077597
Tetrahedron,Enantioselective synthesis of the AB ring system of aklavinone via a chemoenzymatic route,,10.1016/0040-4039(95)00645-s,1995-05-01,0.6492246121016473
Organic Letters,A Concise Enantioselective Synthesis of a Key A-Ring Synthon for 1α-Hydroxyvitamin D<sub>3</sub> Compounds,[figure: see text] This report describes a concise enantioselective synthesis of the A-ring synthon for the synthesis of 1 alpha-hydroxyvitamin D3 compounds. The synthesis involves two notable transformations: (I) stereoselective construction of the enol triflate from the vinyl ketone by Michael addition of Ph2P(O)Li followed by in situ triflation of the resulting enolate and (II) palladium-catalyzed Heck type cyclization of the enol triflate.,10.1021/ol006982u,2001-01-12,0.6492195539823222
Organic Letters,Formal Synthesis of Fostriecin via Asymmetric Alcohol-Mediated Carbonyl Allylation,"A formal synthesis of fostriecin via convergent assembly of two fragments prepared via asymmetric alcohol-mediated C–C coupling is described. One fragment is made by the enantioselective iridium-catalyzed allylation of an allylic alcohol mediated by allyl acetate. The other fragment is made via enantioselective ruthenium-catalyzed reductive syn -(α-alkoxy)allylation of an aldehyde mediated by an alkoxyallene (where 2-propanol is the hydrogen source), representing the first use of this method in target-oriented synthesis. Metathetic fragment union enables interception of a late-stage compound that previously required a 25 step (LLS) synthesis in only 7 steps (LLS).",10.1021/acs.orglett.5c01026,2025-04-10,0.6492166624664919
Organic Letters,Progress toward the Total Synthesis of (+)-Aldosterone:  Synthesis of the A−D Rings,[reaction: see text] Synthesis of the A-D rings of the cortical hormone (+)-aldosterone is described. The key step incorporates a chiral tether in a type 2 intramolecular Diels-Alder reaction that establishes the absolute configuration of four contiguous asymmetric centers. This approach provides an efficient route for either enantiomer of the steroid skeleton.,10.1021/ol034218c,2003-04-11,0.6492129907243221
Organic Letters,"Expeditious Synthesis of Vialinin B, an Extremely Potent Inhibitor of TNF-α Production","A first total synthesis of vialinin B, a powerful inhibitor (IC(50) 20 pM) of TNF-alpha production, is described. The key reactions include a double Suzuki-Miyaura coupling of electron-rich aryl bromide with a couple of phenylboronic acids, a Cu-mediated Ullmann reaction, and a LHMDS-promoted phenylacetylation. This synthesis proceeded in 11 steps with 18% overall yield from a known sesamol derivative.",10.1021/ol9020833,2009-10-05,0.6492095217574028
European Journal of Organic Chemistry,"Stereoselective Synthesis of Lignans of Three Structural Types from a Common Intermediate, Enantioselective Synthesis of (+)‐Yangambin","Abstract Enantioselective total synthesis of (+)‐yangambin was achieved. The key transformation is one‐pot conjugate addition/aldol reaction that involves an enantioenriched benzyl tert ‐butyl sulfoxide, an enone, and gaseous formaldehyde to construct the bis(phenylpropanoid) backbone with excellent stereoselectivity and in good yield. Reduction of the ketone with diisobutylaluminium hydride and acid‐catalysed cyclisation in EtOH furnished (+)‐yangambin in good yield. The resulting synthesis is short, efficient and highly selective. Formation of 2,5‐diaryltetrahydrofuran lignans was observed as a side reaction in the final step of yangambin synthesis. Acid‐catalysed cyclisation of the aldol intermediate gave a completely different outcome. Dehydration to give an enone was followed by two electrophilic aromatic substitution reactions to furnish a derivative of the lignan lirionol.",10.1002/ejoc.201402584,2014-07-21,0.6492029498241758
Organic Letters,A New Radical-Based Route to Calothrixin B,"[structure: see text] A high-yielding totally regioselective intramolecular homolytic acylation of a quinoline ring constitutes the key step in a new synthesis of the pentacyclic indolo[3,2-j]phenanthridine alkaloid calothrixin B.",10.1021/ol052600e,2006-01-25,0.649195981283714
Synlett,Stereoselective Synthesis of (-)-PF1163A via Prins Cyclization,"A highly stereoselective and convergent total synthesis of PF1163 A is described while proving the versatility of Prins cyclization in natural product synthesis. The Prins cyclization, Yamaguchi esterification, and ring-closing metathesis reactions are the key steps utilized in the synthesis of macrolactone.",10.1055/s-0029-1219839,2010-04-16,0.6491813256465002
Journal of the American Chemical Society,Highly Convergent Three Component Benzyne Coupling:  The Total Synthesis of <i>ent</i>-Clavilactone B,"The first total synthesis of (+)-clavilactone B, a potent antifungal agent and novel tyrosine kinase inhibitor, is described. The absolute configuration of clavilactones has been unambiguously established by using Sharpless asymmetric epoxidation to generate the enantiomerically pure substrate. The strategy highlights the use of a powerful and convergent three-component benzyne coupling with a methylallyl Grignard and a chiral epoxy-aldehyde to generate two C-C bonds and install the carbon skeleton of clavilactone. Oxidative lactonization, ten-membered ring construction by ring closing metathesis, and oxidation gave clavilactone B.",10.1021/ja0662671,2006-10-11,0.6491810323062138
Journal of Organic Chemistry,Expedient Access to the Okadaic Acid Architecture:  A Novel Synthesis of the C1−C27 Domain,"A newly designed synthetic entry to the C1-C27 domain of okadaic acid has been developed. This incorporates substantial improvements in the preparations of the key okadaic acid building blocks representing the C3-C8, C9-C14, and C16-C27 portions. The synthesis of the C3-C8 lactone used (R)-glycidol as the origin of the C4 stereogenic center and featured a late-stage optional incorporation of the C7 hydroxyl group. The complementary C9-C14 fragment was synthesized in a concise route from (R)-3-tert-butyldimethylsilyloxy-2-methylpropanal and propargyl bromide. Assembly of the C3-C14 spiroketal-containing intermediate from the constitutent fragments revealed a dramatic effect of C7 functionalization upon spiroketalization efficiency. In contrast, both (9E)- and (9Z)-enones converged readily to the C8 spiroketal upon treatment with acid. Modifications to the central C16-C27 fragment of okadaic acid included the early replacement of benzylic protecting groups by more suitable functionalities to facilitate both the generation of the C15-C27 intermediate and the deprotection of the final products. These modular building blocks were deployed for the synthesis of the C1-C27 scaffold of 7-deoxyokadaic acid. This work demonstrates improvements in the formation of versatile okadaic acid intermediates, as well as a reordering of fragment couplings. This alternative order of coupling was designed to promote the late stage incorporation of nonnatural lipophilic extensions from the C27 terminus.",10.1021/jo001433n,2001-01-09,0.6491443657027525
Angewandte Chemie International Edition,"Divergent Total Synthesis of Euphoranginol C, Euphoranginone D, <i>ent</i>‐Trachyloban‐3β‐ol, <i>ent</i>‐Trachyloban‐3‐one, Excoecarin E, and <i>ent</i>‐16α‐Hydroxy‐atisane‐3‐one","Abstract A divergent synthetic approach to biogenetically related diterpenoids such as ent‐kauranes, ent‐trachylobanes, ent‐beyerane, and ent‐atisane has been developed. The unified synthetic route involves the De Mayo reaction to rapidly generate the bicyclo[3.2.1]‐octane moiety of ent‐kaurane. The key reactions also include bioinspired nucleophilic cyclopropanation generating the [3.2.1.0 2,7 ]‐tricyclic core of ent‐trachylobane and regioselective cyclopropane fragmentation furnishing ent‐beyerane and ent‐atisane through the nucleophilic attack and protonation of the cyclopropane ring. This strategy enables the asymmetric total syntheses of six diterpenoids from the commercially available geraniol.",10.1002/anie.202009128,2020-07-22,0.6491363785956077
Journal of Organic Chemistry,"A Stereoselective and Highly Practical Synthesis of Cytosolic Phospholipase A<sub>2</sub> Substrate, 2-<i>S</i>-Arachidonoyl-1-<i>O</i>-hexadecyl-<i>sn</i>-2-thioglycero-3-<i>O</i>-phosphocholine","The substrate 1 of cytosolic phospholipase A 2 (cPLA 2 ) is an ether-type thiophospholipid with arachidonic acid at the C-2 position and is required for the chromogenic assay for reliable and convenient high throughput screening. The original method of synthesis of 1 has significant problems, resulting in extremely low overall yield and purity. We developed a novel and highly practical method of preparing sufficient quantities of pure 1 for assay. Our synthetic sequence is started with commercially available 1,2- O -isopropylidene- sn -grycerol ( 5 ) and is based on the following key steps: trityl migration reaction of 10 with boron trifluoride etherate to form 13, phosphocholine-forming reaction of 13 to yield 15, and efficient conversion of 15 into 1 by deprotection of a trityl group and condensation with arachidonic acid. Our method offers a practical means of large-scale production of 1 with excellent high chemical purity, because of the introduction of arachidonic acid at the last step of the synthetic sequence.",10.1021/jo970882t,1997-10-01,0.6491330146591683
Organic Letters,Formal Synthesis of (+)-Phomactin A,A concise formal synthesis of (+)-phomactin A has been achieved. The key features of this synthetic strategy involve a one-pot Prins/Conia-ene cyclization protocol for the construction of the highly functionalized 1-oxadeclin core (AB ring) and a late-stage direct γ-hydroxylation of enone for the installation of the C ring.,10.1021/acs.orglett.8b03242,2018-11-27,0.6491306568071835
Synlett,"Novel Approach toward 3,3-Difluoropiperidines from Easily Available Starting Materials and Synthesis of a New Phosphodiesterase Inhibitor","A novel methodology for the synthesis of 3,3-difluoropiperidines has been developed. The target compounds are prepared in three steps using a robust protocol and simple starting materials. The incorporation of the fluorine is achieved by using the cheap and easily available ethyl 2-bromo-2,2-difluoroacetate as building block. Using this methodology, a new potent in vitro phosphodiesterase 2A (PDE2A) inhibitor containing the functionalized fluorinated piperidine scaffold has been prepared.",10.1055/s-0036-1588313,2016-09-12,0.6491200651511652
Journal of Organic Chemistry,"Synthesis of a 6-CF<sub>3</sub>-Substituted 2-Amino-dihydro-1,3-thiazine β-Secretase Inhibitor by <i>N</i>,<i>N</i>-Diethylaminosulfur Trifluoride-Mediated Chemoselective Cyclization","The synthesis of a 6-CF 3 -substituted 2-amino-dihydro-1,3-thiazine via N, N -diethylaminosulfur trifluoride (DAST)-mediated cyclization of N -hydroxypropyl thiourea 6 is described. This reaction gave 6-CF 3 -1,3-thiazine 7 with high chemical yield and chemoselectivity, suppressing the common byproduct of oxazine 8 . This new protocol enabled access to 6-CF 3 -substituted 1,3-thiazine β-secretase inhibitor 2 .",10.1021/acs.joc.8b02179,2018-10-12,0.6491196542212387
Journal of Organic Chemistry,Total Synthesis of GE81112A: An Orthoester-Based Approach,"High Resolution Image Download MS PowerPoint Slide The GE81112 series, consisting of three naturally occurring tetrapeptides and synthetic derivatives, is evaluated as a potential lead structure for the development of a new antibacterial drug. Although the first total synthesis of GE81112A reported by our group provided sufficient amounts of material for an initial in depth biological profiling of the compound, improvements of the routes toward the key building blocks were needed for further upscaling and structure–activity relationship studies. The major challenges identified were poor stereoselectivity in the synthesis of the C -terminal β-hydroxy histidine intermediate and a concise access to all four isomers of the 3-hydroxy pipecolic acid. Herein, we report a second-generation synthesis of GE81112A, which is also applicable to access further representatives of this series. Based on Lajoie’s ortho -ester-protected serine aldehydes as key building blocks, the described route provides both a satisfactory improvement in stereoselectivity of the β-hydroxy histidine intermediate synthesis and a stereoselective approach toward both orthogonally protected cis and trans -3-hydroxy pipecolic acid.",10.1021/acs.joc.3c00094,2023-04-06,0.6491191134612208
Tetrahedron,syn-Selective additions to Garner aldehyde: synthesis of a potent glucosylceramide synthase inhibitor,,10.1016/s0040-4039(02)02096-8,2002-11-01,0.6491036340396349
Organic Letters,Enantioselective Total Synthesis of (−)-Hamigeran F and Its Rearrangement Product,"Herein, we report the first enantioselective total synthesis of the highly complex hamigeran diterpenoid (-)-hamigeran F and its rearrangement product. The synthetic strategy features key steps of asymmetric hydrogenation, Horner-Wadsworth-Emmons olefination, and intramolecular Friedel-Crafts acylation to construct the [6,6,5]-tricyclic skeleton bearing three consecutive stereocenters, a sequence of steps involving Rosenmund reduction, Wittig reaction, dihydroxylation to assemble the α-acetoxy ketone group, and an intramolecular aldol reaction to build the tetracyclic core structure.",10.1021/acs.orglett.2c01997,2022-07-11,0.6490889142431239
Journal of Organic Chemistry,A New Synthesis of Enantiopure Amine Fragment: An Important Intermediate to the Anti-HIV Drug Lenacapavir,"High Resolution Image Download MS PowerPoint Slide Herein, we describe a new seven-step approach to prepare ( S )-1-(3,6-dibromopyridin-2-yl)-2-(3,5-difluorophenyl)ethan-1-amine (( S )- 4 ) from the inexpensive 2-(3,5-difluorophenyl)acetic acid. The key steps in the sequence include (1) the Weinreb amide-based ketone synthesis to provide an entry point to the core structure; (2) simple functional group transformations to afford the racemic amine 4 - rac; and (3) dynamic kinetic resolution (DKR) to access the chiral amine ( S )- 4 . This seven-step process delivered the enantiopure amine ( S )- 4 in an overall isolated yield of approximately 15%. The process was demonstrated on a decagram scale, and the process requires no chromatographic purifications. Single-crystal X-ray crystallography measurements verified the chiral amine structure and absolute configuration.",10.1021/acs.joc.4c02380,2024-12-16,0.6490782855057606
Journal of the American Chemical Society,Concise Enantioselective Total Synthesis of (+)-Punctaporonin U,"We report herein the first enantioselective total synthesis of (+)-punctaporonin U, a cage-like pentacyclic sesquiterpene bearing eight contiguous stereocenters. The synthesis features three key transformations: a) a rare cis -selective Mukaiyama-Michael addition of the silyl enol ether derived from 2,2-dimethylcyclobutan-1-one to 4-[( tert -butyldimethylsilyl)oxy]cyclopent-2-en-1-one; b) a domino oxa-Michael addition/aldol reaction/bromination sequence that constructs both a fused five-membered ring and a 1,4-bridged 7-membered ring; c) an intramolecular S N 2 displacement to install the 1,3-bridged tetrahydrofuran ring. The synthesis is accomplished in six steps from 4-[( tert -butyldimethylsilyl)oxy]cyclopent-2-en-1-one, which itself is accessible in five steps from cyclopentadiene.",10.1021/jacs.5c15423,2025-10-22,0.6490738696908847
Organic Process Research & Development,An Improved Process for the Preparation of Diphenylmethyl 7β-Phenylacetamido-3-hydroxymethyl-3-cephem-4-carboxylate,"An efficient and improved process for the preparation of diphenylmethyl 7β-phenylacetamido-3-hydroxymethyl-3-cephem-4-carboxylate was developed. With the commercially available 7-aminocephalosporanic acid (7-ACA) as starting material, up to 73.5% overall isolated yield of the titled compound was synthesized in two steps via direct phenylacetylation with phenylacetyl chloride, followed by basic hydrolysis and esterification with diphenyldiazomethane. The newly developed process obviated the use of protecting groups, reduced the environmental footprint, and could be easily controlled and conveniently scaled up for this pivotal intermediate in cephalosporin chemistry.",10.1021/op900063e,2009-05-28,0.6490602010294096
Tetrahedron,An improved synthesis of methyl N-trifluoroacetyl-6-hydroxy-α-L-daunosaminide,,10.1016/0040-4039(92)80015-c,1992-06-01,0.6490583710322111
Tetrahedron,An improved synthesis of methyl n-trifuoroacetyl-6-hydroxy-α-l-daunosaminide,,10.1016/s0040-4039(00)92004-5,1992-06-23,0.6490583710322111
Tetrahedron,"An all-cis 3,4-dihydroxy-5-aminopiperidine by a novel route to deoxydiamino sugars",,10.1016/s0040-4039(99)00156-2,1999-03-01,0.6490580687570352
European Journal of Organic Chemistry,Synthetic Route to Rare Isoindolones Derivatives,"Abstract The isoindolone scaffold is present in many biologically active compounds. Here, we have developed a shorter and more efficient synthesis of tetrahydropyrido[2,1‐ a ]isoindolone. The key step of this approach is a cyclization to form the γ‐lactam ring under Shibasaki's conditions. Thus, tetrahydropyrido[2,1‐ a ]isoindolone and superior analogues, namely hexahydroazepino[2,1‐ a ]isoindolone and hexahydroazocino[2,1‐ a ]isoindolone, have been prepared in only three steps in 39, 25, and 19 % overall yields, respectively. This novel strategy offers a shorter alternative to existing procedures.",10.1002/ejoc.201403649,2015-02-23,0.6490547000520474
Journal of Organic Chemistry,Asymmetric Synthesis of the <i>epi</i>-Vinigrol Tricyclic Core Enabled by a Wolff Rearrangement Strategy and Formal Total Synthesis of (−)-Vinigrol,"A new approach to construct the tricyclic framework of the diterpenoid vinigrol is described. The challenging 1,5-butanodecahydronaphthalene core was established efficiently and diastereoselectively through a combination of type II [5 + 2] cycloaddition and Wolff rearrangement. In addition, a formal total synthesis of (-)-vinigrol was achieved in 12 steps, in which Baran's intermediate was efficiently produced from a known compound by a two-step sequence involving a stereoselective α-hydroxylation and a diastereoselective α-ketol rearrangement.",10.1021/acs.joc.3c01729,2023-10-11,0.6490486797994608
Organic Process Research & Development,Process Development of Selectively Benzoylated and Fluorinated Glycosyl Donors,"Route selection, process development and large-scale preparation of selectively benzoylated and fluorinated d -glucopyranoses, required as glycosyl donors for the synthesis of the SGLT inhibitor SAR7226, are discussed.",10.1021/op100053k,2010-05-03,0.6490457997385907
Journal of Organic Chemistry,Formal Total Synthesis of the Potent Renin Inhibitor Aliskiren:  Application of a SmI<sub>2</sub>-Promoted Acyl-like Radical Coupling,"A formal total synthesis of the potent renin inhibitor aliskiren is disclosed exploiting an alternative coupling strategy recently developed by this laboratory for the preparation of the hydroxyethylene isostere-based class of protease inhibitors. The thioester derivative of the amino acid representing the C5-C9 fragment of the aliskiren carbon skeleton underwent a carbon chain extension via a SmI2-promoted radical addition to n-butyl acrylate. Introduction of the C3-isopropyl group with the correct relative configuration was accomplished via stereoselective reduction of the obtained ketone with concomitant lactonization, followed by an aldol reaction with acetone. Further functional group and protecting group manipulation culminated in a formal total synthesis of aliskiren in 10 steps from the corresponding fully protected non-natural amino acid.",10.1021/jo060296c,2006-05-23,0.6490330325886791
Synlett,Syntheses of Novel (<i>E</i>)-<i>N</i>-Methyl-2-styryl-4-quinolones,"Two new synthetic routes for (E)-N-methyl-2-styryl-4-quinolones have been established, both starting from (E)-2′-cinnamoylaminoacetophenones. In the first, (E)-2′-cinnamoylamino­acetophenones are cyclized and then methylated, while in the second they are methylated followed by in situ cyclization.",10.1055/s-0028-1083530,2008-10-01,0.6490163470157735
Tetrahedron,"Synthesis of new diheteroarylcarbazoles: a facile and simple route of 3,6-di(pyrazol-4-yl)carbazoles",,10.1016/j.tetlet.2006.08.087,2006-09-15,0.6489995960666057
Angewandte Chemie International Edition,Protecting‐Group‐Free Enantioselective Synthesis of (−)‐Pallavicinin and (+)‐Neopallavicinin,"The first enantioselective synthesis of (-)-pallavicinin and (+)-neopallavicinin has been achieved in 15 steps. The described synthesis avoids protecting-group manipulations by synthesis designs predicated on highly chemo- and stereoselective transformations. Highlights of the synthesis include a palladium-catalyzed enantioselective decarboxylative allylation to form the chiral all-carbon quaternary stereocenter, a palladium-catalyzed oxidative cyclization to assemble the [3.2.1]-bicyclic moiety, and an unprecedented LiBHEt3-induced fragmentation/protonation of an α-hydroxy epoxide to form the α-furan ketone with the desired configuration.",10.1002/anie.201506575,2015-09-14,0.6489294922304192
Tetrahedron,A potent inhibitor of β--acetylglucosaminidases: 6-acetamido-6-deoxycastanospermine,,10.1016/s0040-4039(00)74866-0,1991-02-01,0.6489246050749989
Tetrahedron,"Lecythophorin, a potent inhibitor of blue-stain fungi, from the hyphomycetous fungus Lecythophora hoffmannii",,10.1016/0040-4039(95)01751-3,1995-10-01,0.6489246050749989
Synlett,An Enantioselective Total Synthesis of (-)-Stemoamide,An enantioselective synthesis of (-)-stemoamide has been achieved in 14 steps starting from pyroglutamyl alcohol in ca. 7% overall yield. The key steps in the strategy are a conjugate addition of a vinyl copper reagent and a ring closing metathesis (RCM) reaction to form the seven-membered ring.,10.1055/s-2004-822927,2004-01-01,0.6489203659805953
Journal of Organic Chemistry,"A Concise, Gram-Scale Total Synthesis of Protectin DX and Related Labeled Versions via a Key Stereoselective Reduction of Enediyne","We report a gram-scale total synthesis of protectin DX (PDX) following a convergent synthetic route (24 steps) from l -malic acid. This novel synthetic strategy is based on the assembly of three main building blocks using a Sonogashira coupling reaction (blocks A and B) and Wittig olefination (block C) to provide the 22-carbon backbone of PDX. A key stereoselective reduction of enediyne leads to a central E, Z, E -trienic system of PDX and also gives access to its labeled versions (D and T).",10.1021/acs.joc.3c00360,2023-05-12,0.6489117583726596
Journal of the American Chemical Society,Total Synthesis of Platensimycin and Related Natural Products,"Platensimycin is the flagship member of a new and growing class of antibiotics with promising antibacterial properties against drug-resistant bacteria. The total syntheses of platensimycin and its congeners, platensimycins B(1) and B(3), platensic acid, methyl platensinoate, platensimide A, homoplatensimide A, and homoplatensimide A methyl ester, are described. The convergent strategy developed toward these target molecules involved construction of their cage-like core followed by attachment of the various side chains through amide bond formation. In addition to a racemic synthesis, two asymmetric routes to the core structure are described: one exploiting a rhodium-catalyzed asymmetric cycloisomerization, and another employing a hypervalent iodine-mediated de-aromatizing cyclization of an enantiopure substrate. The final two bonds of the core structure were forged through a samarium diiodide-mediated ketyl radical cyclization and an acid-catalyzed etherification. The rhodium-catalyzed asymmetric reaction involving a terminal acetylene was developed as a general method for the asymmetric cycloisomerization of terminal enynes.",10.1021/ja9068003,2009-10-29,0.6488983053939611
Organic Letters,Enantiospecific Synthesis of <i>N</i>-Boc-Adda:  A Linear Approach,"[structure: see text] Synthesis of the unusual amino acid (2S,3S,8S, 9S)-3-amino-9-methoxy-2,6,8-trimethyl-10-phenyl-4,6-decadienoic acid (Adda), a unit of numerous cyanobacterial toxins, is described. Construction of the target molecule was achieved in 13 steps with an overall yield of 40%. The work is highlighted by a novel one-pot transformation from isoxazolidin-5-one intermediate 6 to the final product, a step that can also be used to form beta-amino acids.",10.1021/ol006347o,2000-08-10,0.6488970585877133
Angewandte Chemie International Edition,Bioinspired and Concise Synthesis of (±)‐Stemoamide,Natural inspiration: A concise total synthesis of (±)-stemoamide was completed in eight steps with a 37 % overall yield. A bioinspired N-acyliminium ion cyclization and an unprecedented dynamic ruthenium-catalyzed cyclocarbonylation ensured the high efficiency of the synthesis. A novel silver-mediated cyclization of an allenic alcohol shows potential for the future asymmetric synthesis of the target. TMS=trimethylsilyl.,10.1002/anie.201005833,2011-02-17,0.6488505356017855
Synthesis,"Stereoselective Total Synthesis of (3R,5R)-5-Hydroxy-de-O-methyllasiodiplodin via the Prins Cyclization","A practical stereoselective total synthesis of (3R,5R)-5-hydroxy-de-O-methyllasiodiplodin has been accomplished via Prins cyclization. It exhibits potato microtuber inducing activity. The synthetic sequence involves Prins cyclization, reductive opening of the pyran ring, esterification, and ring-closing metathesis (RCM) as the key steps.",10.1055/s-0030-1258244,2010-09-07,0.648845541914776
Journal of Organic Chemistry,"Asymmetric Synthesis of the Potent HIV-Protease Inhibitor, Nelfinavir","An asymmetric synthesis of nelfinavir is described starting from acrolein and (S)-methyl phenyl sulfoxide. The key features include (a) stereoselective preparation of a beta-protected amino-gamma,delta-unsaturated sulfoxide by the reaction of an alpha-sulfinyl carbanion with an unsaturated t-butyl sulfinylimine, (b) stereoselective bromohydrin formation using the pendant sulfoxide group as an intramolecular nucleophile, and (c) use of commercially or readily prepared inexpensive starting materials.",10.1021/jo902048t,2009-12-14,0.6488342132831706
European Journal of Organic Chemistry,Enantioselective Total Synthesis of (–)‐Subglutinols A and B: Potential Immunosuppressive Agents Isolated from a Microorganism,"Abstract Potential immunosuppressive diterpenoid pyrones (–)‐subglutinols A and B were efficiently synthesized in an enantioselective manner starting from a known trans ‐decalone derivative. The synthetic method involved the following key steps: (i) [2,3]‐Wittig rearrangement of a stannyl methyl ether to access the requisite decalin segment; (ii) coupling of the decalin segment with a γ‐pyrone moiety to set up the desired carbon framework; (iii) construction of a characteristic tetrahydrofuran ring in one‐pot fashion through an internal S N 2‐type cyclization, and (iv) conversion of a γ‐pyrone moiety into an α‐pyrone ring to yield the target (–)‐subglutinols A and B.",10.1002/ejoc.201100517,2011-07-21,0.648833252215161
Organic Letters,Total Synthesis of (±)-Decinine via an Oxidative Biaryl Coupling with Defined Axial Chirality,The total synthesis of (±)-decinine has been achieved. The key steps in the synthesis involved the formation of lasubine II via a gold catalyzed annulation of 1-(but-3-yn-1-yl)piperidine and the formation of the 12-membered ring of decinine (1) with complementary atropselectivity via a VOF3-mediated oxidative biaryl coupling reaction.,10.1021/ol3015573,2012-06-29,0.6488332439097197
Organic Letters,A Stereoselective Synthesis of Digitoxin and Digitoxigen Mono- and Bisdigitoxoside from Digitoxigenin via a Palladium-Catalyzed Glycosylation,"A convergent and stereocontrolled route to trisaccharide natural product digitoxin has been developed. The route is amenable to the preparation of both the digitoxigen mono- and bisdigitoxoside. This route featured the iterative application of the palladium-catalyzed glycosylation reaction, reductive 1,3-transposition, diastereoselective dihydroxylation, and regioselective protection. The natural product digitoxin was fashioned in 15 steps starting from digitoxigenin 2 and pyranone 8a or 18 steps from achiral acylfuran.",10.1021/ol061683b,2006-08-18,0.648832119694362
Journal of the American Chemical Society,Enantioselective Total Synthesis of the Potent Antitumor Agent (−)-Mucocin Using a Temporary Silicon-Tethered Ring-Closing Metathesis Cross-Coupling Reaction,"The enantioselective total synthesis of the annonaceous acetogenin (-)-mucocin (1) was accomplished using a triply convergent 12-step sequence (longest linear sequence) in 13.6% overall yield. This represents the first application of the temporary silicon-tethered (TST) ring-closing metathesis (RCM) cross-coupling reaction and the enantioselective alkyne/aldehyde addition to the synthesis of a complex annonaceous acetogenin. Moreover, all three fragments required for the coupling reactions are conveniently prepared in 5-6 steps from two readily available enantiomerically enriched epoxides. Finally, this synthesis stimulated the development of a new approach for the construction of 3-hydroxy-2,6-disubstituted tetrahydropyrans, using the bismuth tribromide-mediated reductive etherification reaction, which represents a motif that is prevalent in a wide range of pharmacologically significant natural products.",10.1021/ja0384734,2003-11-05,0.6488315765831736
Journal of Organic Chemistry,Total Synthesis of Iejimalide B,"Iejimalide B, a structurally unique 24-membered polyene macrolide having a previously underutilized mode of anticancer activity, was synthesized according to a strategy employing Julia-Kocienski olefinations, a palladium-catalyzed Heck reaction, a palladium-catalyzed Marshall propargylation, a Keck-type esterification, and a palladium-catalyzed macrolide-forming, intramolecular Stille coupling of a highly complex cyclization substrate. The overall synthesis is efficient (19.5% overall yield for 15 linear steps) and allows for more practical scaled-up synthesis than previously reported strategies that differed in the order of assembly of key subunits and in the method of macrocyclization. The present synthesis paves the way for efficient preparation of analogues for drug development efforts.",10.1021/jo200514m,2011-04-13,0.6487634224894009
Journal of Organic Chemistry,Nucleophilic Ring-Opening of Epoxide and Aziridine Acetates for the Stereodivergent Synthesis of β-Hydroxy and β-Amino γ-Lactams,"A highly regio- and stereoselective synthesis of novel β,γ-disubstituted γ-lactams with either an anti or syn relative configuration was developed from readily available epoxide and aziridine acetates. The key steps include the regio- and diastereocontrolled nucleophilic ring-opening of these three-membered heterocycles followed by mild reductive cyclization of the γ-azido ester intermediate. The method was also extended to an asymmetric synthesis of (4R,5S)-4-hydroxy-5-phenylpyrrolidin-2-one from a chiral epoxide acetate. The main features of this versatile synthesis of functionalized γ-lactams include the involvement of inexpensive reagents and mild conditions together with high chemical efficiency.",10.1021/jo102267h,2010-12-31,0.6487616346086852
Journal of the American Chemical Society,Enantioselective Total Synthesis of (+)-Gliocladine C: Convergent Construction of Cyclotryptamine-Fused Polyoxopiperazines and a General Approach for Preparing Epidithiodioxopiperazines from Trioxopiperazine Precursors,"A concise second-generation total synthesis of the fungal-derived alkaloid (+)-gliocladin C (11) in 10 steps and 11% overall yield from isatin is reported. In addition, the epipolythiodioxopiperazine (ETP) natural product (+)-gliocladine C (6) has been prepared in six steps and 29% yield from the di-(tert-butoxycarbonyl) precursor of 11. The total synthesis of 6 constitutes the first total synthesis of an ETP natural product containing a hydroxyl substituent adjacent to a quaternary carbon stereocenter in the pyrrolidine ring.",10.1021/ja201789v,2011-04-07,0.6487503037440004
Organic Process Research & Development,The Development of a Dimroth Rearrangement Route to AZD8931,"Recently, the aminoquinazoline motif has been highly prevalent in anticancer pharmaceutical compounds. Synthetic methods are required to make this structure on a multikilo scale and in high purity. The initial route to aminoquinazoline AZD8931 suffered from the formation of late-stage impurities. To avoid these impurities, a new high-yielding Dimroth rearrangement approach to the aminoquinazoline core of AZD8931 was developed. Assessment of route options on a gram scale demonstrated that the Dimroth rearrangement is a viable approach. The processes were then evolved for large-scale production with learning from a kilo campaign and two plant-scale manufactures. Identification of key process impurities offers an insight into the mechanisms of the Dimroth rearrangement as well as the hydrogenation of a key intermediate. The final processes were operated on a 30 kg scale delivering the target AZD8931 in 41% overall yield.",10.1021/acs.oprd.6b00412,2017-02-01,0.6487335753597318
Tetrahedron,"Novel generation of conjugated alkynyl ketenes: Efficient synthesis of β,γ-alkynyl lactones",,10.1016/s0040-4039(00)60348-9,1993-03-01,0.6487231038063515
Synlett,Iridium-Catalysed C–H Borylation Facilitates a Total Synthesis of the HRV 3C Protease Inhibitor (±)-Thysanone,A new total synthesis of the HRV 3C protease inhibitor (±)-thysanone is described. The synthetic route hinges on an iridium-catalysed borylation to install the resorcinol-derived component of the natural product.,10.1055/s-0033-1340495,2014-01-10,0.64870661285022
Synlett,"TBAHS-Catalyzed Synthesis of 2-Dihydroquinazolin-2-ylquinoline: An Efficient and Practical Synthesis of Naturally Occurring Alkaloids Luotonin A, B, and E","A synthesis of 2-dihydroquinazolin-2-ylquinoline using a phase-transfer catalyst (TBAHS) in semi-aqueous phase, followed by Mitsunobu cyclization as key steps for an efficient and practical synthesis of naturally occurring alkaloids luotonin A, B, and E starting from o -nitrobenzaldehyde is reported. The new approach presents the advantage of a shorter route with high overall yield (57%, 45%, and 37%, respectively) and ease of operation.",10.1055/s-0032-1316537,2012-06-29,0.6487033247462929
Synthesis,Total Synthesis of (-)-Invictolide,"A convergent approach to the total synthesis of (–)-invictolide, a component of the queen recognition pheromone of Solenopsis­ invicta , is described. Key steps involve the desymmetrization of a bicyclic olefin with Brown’s chiral hydroboration, C–C bond formation, 1,3- syn reduction, and oxidative lactonization of a 1,3,5-triol with TEMPO/PhI(OAc) 2 .",10.1055/s-0032-1316561,2012-07-06,0.6486951049265249
Synthesis,Syntheses of Carpyrinic Acid and of Related Pyridines with Long Aliphatik Chains,"All articles of this category Four different syntheses of carpyrinic acid, i.e. 8-(5-hydroxy-6-methyl-2-pyridyl)octanoic acid, are reviewed in this paper and the synthetic value of individual steps is compared and discussed. The synthesis of another type of a long-chain pyridine derivative is presented, namely that of dehydroprosopine [5-hydroxy-2-(11-hydroxydodecyl)-6-hydroxymethylpyridine] which is a key intermediate in the total synthesis of the alkaloids prosopine and prosopinine. Finally, the syntheses of the ant venoms of related structures via the corresponding pyridines are reviewed. The long-chain pyridines are potential intermediates for a large group of piperidine derivatives of considerable and manyfold biological interest. 1. Syntheses of Carpyrinic Acid 1.1 Rapoport's Synthesis 1.2 Govindachari's Synthesis 1.3 Gruber's Synthesis 1.4 A Novel Synthesis 2. Synthesis of (±) 5-Hydroxy-2-(11-hydroxydodecyl)-6-hydroxymethylpyridine (Dehydroprosopine) 3. Synthesis of Ant Venoms (2-Methyl-6-alkyl- and -6-alkenyl-pyridines, their Derivatives and Homologs).",10.1055/s-1972-21900,1972-01-01,0.6486764326272642
Synthesis,Selective<i>o</i>-Vinylation of Phenols; Synthesis of 2-(1-Phenylethenyl)-phenols,,10.1055/s-1977-24292,1977-01-01,0.6486717870198978
Tetrahedron,"Enantio- and stereo-selective synthesis of 2,6-dideoxyhexoses from divinylcarbinol",,10.1016/s0040-4039(00)84985-0,1986-01-01,0.6486717870198978
Tetrahedron,Selective synthesis of enethiols,,10.1016/s0040-4039(00)60029-1,1992-10-01,0.6486717870198978
Tetrahedron,A first selective synthesis of cyclopentaveratrylene,,10.1016/s0040-4039(00)77079-1,1994-07-01,0.6486717870198978
Organic Letters,First Asymmetric Total Synthesis of (+)-Sparteine,"[reaction: see text] The total synthesis of (+)-sparteine was accomplished from 2,5-norbornadione in 15 steps and 15.7% overall yield. The key steps were two ring-expansion reactions, one involving an intramolecular Schmidt reaction and one using a novel variant of the photo-Beckmann rearrangement.",10.1021/ol026230v,2002-06-29,0.648664768214002
Organic Letters,Rapid Construction of the ABC Ring System in the <i>Daphniphyllum</i> Alkaloid Daphniyunnine C,An efficient and scalable synthesis of the ABC ring system common to the calyciphylline A-type alkaloids has been developed. The tricyclic core of the alkaloids features a bowl-shaped [6-6-5] skeleton with five stereogenic centers including an all-carbon quaternary center. It was constructed rapidly from a readily available carvone derivative through a seven-step sequence involving an aza-Michael addition and Pd-catalyzed enolate α-vinylation as key steps.,10.1021/ol3026395,2012-10-24,0.6486612286535351
Tetrahedron,Artificial intelligence designed drug synthesis: One-pot preparation of trans β-lactams and application to cholesterol absorption inhibitor SCH 47949 synthesis,,10.1016/j.tetlet.2019.07.033,2019-07-17,0.6486529521657102
Journal of the American Chemical Society,Enantioselective Total Synthesis of Guanacastepene N Using an Uncommon 7-Endo Heck Cyclization as a Pivotal Step,"A convergent, enantioselective total synthesis of (+)-guanacastepene N was developed that features a 7-endo Heck cyclization as the key step. In the course of this synthesis, short syntheses of the enantiomerically pure cyclopentenone and cyclohexene building blocks 5 and 6, which constitute A and C ring fragments of guanacastepene N, were developed. These fragments were linked by a challenging conjugate addition reaction that also generated the C11 quaternary carbon stereocenter. Regioselective 7-endo Heck cyclization gave rise to a tricyclic intermediate, which was elaborated to complete the first total synthesis of guanacastepene N and the second enantioselective total synthesis of a guanacastepene natural product.",10.1021/ja0650504,2006-09-19,0.6486426361006128
Organic Process Research & Development,Novel and Practical Synthesis of Triantennary <i>N</i>-Acetylgalactosamine Ligands for Liver-Targeted Delivery of siRNA Therapeutics,"A novel and efficient synthetic approach for triantennary N -acetylgalactosamine is presented. A strategically designed convergent synthetic route was developed, successfully completing the target molecule in 16 steps. The key innovation is a pioneering amide condensation reaction between building blocks 46 and 48, yielding intermediate 40 with a significantly enhanced yield (77.6%) compared to that of conventional methods. This optimized protocol exhibits remarkable operational simplicity. Most intermediates required simple purification or were directly used in subsequent reactions without isolation. The target compound was ultimately obtained in outstanding yield (10.2%) with excellent purity (99.66%). Comprehensive structural verification was conducted via 1 H NMR and HRMS analyses for all synthesized compounds, complemented by 13 C NMR characterization for critical intermediates.",10.1021/acs.oprd.5c00122,2025-07-18,0.6486297780990026
Journal of the American Chemical Society,"Total Synthesis of (±)-Jiadifenin, a Non-peptidyl Neurotrophic Modulator","We report the first total synthesis of jiadifenin (1), the establishment of a modality for its biological evaluation, and the discovery of apparently more potent neurotrophic activity in fully synthetic compound 17, an intermediate en route to 1.",10.1021/ja045939p,2004-10-16,0.6486276827451234
Synthesis,A Convenient Synthesis of L-α-Vinylglycine from D-Mannitol,"(opens in new window) Buy Article (opens in new window) Permissions and Reprints (opens in new window) All articles of this category (opens in new window) A novel procedure is described for the synthesis of L -α -vinylglycine based on the diastereoselective addition of vinylmagnesium bromide to the N -benzyl imine derived from 2,3- 0 -isopropylidene-D-glyceraldehyde. The route developed is both convenient (only one diastereoisomer is obtained in the addition reaction) and efficient (45% overall yield over 7 steps). diastereoselective organometallic addition - D-mannitol - L -α -vinylglycine - asymmetric synthesis - α -amino acids",10.1055/s-1997-3184,1997-07-01,0.6486111536969276
Organic Process Research & Development,"A Novel and Practical Synthesis of 5-Fluoro-1-(2-fluorobenzyl)-1<i>H</i>-pyrazolo[3,4-<i>b</i>]pyridine-3-carbonitrile, a Key Intermediate of Vericiguat","5-Fluoro-1-(2-fluorobenzyl)-1 H -pyrazolo[3,4- b ]pyridine-3-carbonitrile ( 9 ) was a key intermediate for the preparation of vericiguat ( 1 ). A new approach for the synthesis of 9 was developed from 2-chloro-5-fluoronicotinic acid ( 22 ), a commercially available material, in an overall yield of 48.3%. The hydrazinolysis and intramolecular substitution were completed in one step to obtain 5-fluoro-1 H -pyrazolo[3,4- b ]pyridin-3-ol ( 26 ). N-1 benzylation of 26 afforded 5-fluoro-1-(2-fluorobenzyl)-1 H -pyrazolo[3,4- b ]pyridin-3-ol ( 27 ), whose structure was confirmed by 1 H and 13 C NMR spectroscopy, mass spectrometry, and single-crystal X-ray crystallography. Pd-catalyzed cyanation of 5-fluoro-1-(2-fluorobenzyl)-3-bromo-1 H -pyrazolo[3,4- b ]pyridine ( 28 ) was applied to prepare key intermediate 9 . In the route, compounds 26, 27, and 28 have not been reported in the previous literature.",10.1021/acs.oprd.3c00011,2023-03-30,0.6485884851898935
Journal of Organic Chemistry,"Synthesis of a Basket-Shaped C<sub>56</sub>H<sub>38</sub> Hydrocarbon as a Precursor toward an End-Cap Template for Carbon [6,6]Nanotubes","A basket-shaped C(56)H(38) hydrocarbon (3) possessing a 30-carbon difluorenonaphthacenyl core that can be mapped onto the surface of C(78) was synthesized from 4-bromo-1-indanone. The first stage of the synthesis involved the preparation of tetraketone 10 as a key intermediate. The use of cascade cyclization reactions of benzannulated enyne-allenes as key features in the next stage of the synthetic sequence provides an efficient route to 3 from 4-bromo-1-indanone in 12 steps. The all-cis relationship among the methyl groups and the methine hydrogens causes the two benzofluorenyl units in 3 to be in an essentially perpendicular orientation to each other. Hydrocarbon 3 and its derivatives could serve as attractive precursors leading to a geodesic C(68)H(26) end-cap template for carbon [6,6]nanotubes.",10.1021/jo100132v,2010-02-24,0.6485729520950375
Journal of the American Chemical Society,A Global and Local Desymmetrization Approach to the Synthesis of Steroidal Alkaloids: Stereocontrolled Total Synthesis of Paspaline,"A stereocontrolled total synthesis of the indole diterpenoid natural product paspaline is described. Key steps include a highly diastereoselective enzymatic desymmetrization, substrate-directed epoxidation, Ireland-Claisen rearrangement, and diastereotopic group selective C-H acetoxylation to assemble the target with excellent stereofidelity. The route and results described herein outline complementary conceptual disconnections in the arena of steroid natural product synthesis.",10.1021/jacs.5b02631,2015-04-09,0.6485531329338781
Journal of the American Chemical Society,A General Strategy to Elisabethane Diterpenes:  Stereocontrolled Synthesis of Elisapterosin B via Oxidative Cyclization of an Elisabethin Precursor,"Described is an efficient synthesis of the complex bioactive natural product, elisapterosin B, a potent in vitro inhibitor of Mycobacterium tuberculosis H37Rb. The synthesis elisapterosin B, prepared in its enantiomeric form, proceeds by a highly stereocontrolled sequence commencing with a simple glutamic acid derived compound. Pivotal steps in the sequence include (a) a pinacol-type ketal rearrangement to transfer chirality, (b) an IMDA reaction of an E,Z-diene to construct the elisabethin skeleton, and (c) a biosynthesis-inspired oxidative cyclization of the elisabethin precursor to elisapterosin B.",10.1021/ja035898h,2003-10-01,0.6485374845632659
Journal of Organic Chemistry,Concise Synthesis of the Macrocyclic Core of Rhizopodin by a Heck Macrocyclization Strategy,A highly convergent synthesis of the central dimeric core of the potent antibiotic macrolide rhizopodin is reported. Notable features of the highly concise route include an effective preparation of the key C8-C22 building block based on an iridium-catalyzed Krische allylation and a chemoselective cross-coupling approach toward the macrocycle involving a highly advantageous Heck reaction for macrocyclization.,10.1021/jo302134y,2012-11-16,0.6485365012654383
Journal of Organic Chemistry,Total Synthesis of the Ansamycin Antibiotic (+)-Thiazinotrienomycin E,"The first total synthesis of (+)-thiazinotrienomycin E (1), member of a novel class of cytotoxic ansamycin antibiotics, has been achieved. Key features of the synthetic strategy include (a) the efficient construction of sulfone 7 incorporating TBS protection of the aniline, (b) an improved synthesis of allyl chloride (-)-6, the advanced intermediate employed in our trienomycins A and F total syntheses, (c) application of the Kocienski modified Julia protocol to elaborate the E,E,E-triene subunit in a stereo-controlled fashion, (d) an efficient union of sulfone 7 with advanced iodide 62, and (e) Mukaiyama macrolactamization to access the thiazinotrienomycin macrocyclic ring.",10.1021/jo991958j,2000-05-11,0.648518602968772
Organic Letters,Synthesis of 3-Azidopiperidine Skeleton Employing Ceric Ammonium Nitrate (CAN)-Mediated Regioselective Azidoalkoxylation of Enol Ether: Total Synthesis of D<sub>2</sub> Receptor Agonist (±)-Quinagolide,"receptor agonist, was accomplished via a ceric ammonium nitrate (CAN)-mediated regioselective azidoalkoxylation of enol ether route. Key features of the synthesis include Claisen rearrangement, PPTS (pyridinium p-toluenesulfonate)-catalyzed one-pot acetal deprotection, followed by a diastereoselective Henry reaction, which enables construction of the required trans ring junction and CAN-mediated regioselective azidoalkoxylation of enol ether. The PPTS-catalyzed intramolecular diastereoselective Henry reaction to fix three contiguous stereocenters on tetrahydronaphthalene and the first-of-its-kind synthesis of the 3-azidopiperidine skeleton, using a CAN-mediated regioselective azidoalkoxylation of enol ether, are important findings of the present work.",10.1021/acs.orglett.8b02900,2018-11-05,0.6485184398246608
Organic Process Research & Development,"Pilot Plant Preparation of an α<sub>v</sub>β<sub>3</sub> Integrin Antagonist. Part 1. Process Research and Development of a (<i>S</i>)-β-Amino Acid Ester Intermediate:  Synthesis via a Scalable, Diastereoselective Imino-Reformatsky Reaction","Described are four process research investigations directed toward discerning a scalable, enantioselective method for preparing ( S )-β-amino acid ester 3, a key intermediate to the α v β 3 integrin antagonist 1 . Reported are an asymmetric Michael reaction approach, attempts to enantioselectively hydrogenate an enamine, resolution of (±)- 3 via diastereomeric salt formation, and a synthetic route employing a novel, diastereoselective imino-Reformatsky reaction. This last research initiative proved successful and was employed as the enabling route to initial API supply. Process development of this enabling chemistry is reported. The technical issues researched and optimized were (1) the necessity of employing MEM-protection for high yield and diastereoselectivity in the imino-Reformatsky reaction, (2) the reaction kinetics of MEM chloride hydrolysis and the application of these data to an on-scale quench procedure, (3) the efficient formation of the ( S )-phenylglycinol imine 15 in NMP and a dehydration of this product solution on-scale, employing molecular sieves, (4) a calorimetric study of the Reformatsky reaction and the application of these data, (5) the replacement of Pb(OAc) 4 with NaIO 4 and the use of methylamine to sequester competing oxazolidine formation, and (6) further development of the isolation and purification protocol for the ethyl ester, p -TsOH salt of ( S )- 3 . The results and challenges associated with two campaigns in which the potential commercial process was practiced are discussed.",10.1021/op034094j,2003-12-18,0.6485060453912241
Journal of Organic Chemistry,A Convenient New Synthesis of Benzo[<i>a</i>]pyrene,"A convenient new synthesis of the ubiquitous environmental carcinogen benzo[a]pyrene (BaP) is described. In the key step, the method entails Suzuki coupling of naphthalene 2-boronic acid with 2-bromobenzene-1,3-dialdehyde and requires only three steps. It is considerably shorter and simpler than the older methods and provides BaP in higher overall yield.",10.1021/jo030313n,2004-01-22,0.6484875411620397
Organic Letters,Efficient Short Step Synthesis of Corey's Tamiflu Intermediate,Corey's tamiflu intermediate was synthesized from a bicyclolactam adduct obtained by base-catalyzed Diels-Alder reaction of N-nosyl-3-hydroxy-2-pyridone with ethyl acrylate. A compound that has the same array of functional groups with the Corey's intermediate was obtained in four steps from the DA adduct in 47% overall yield. The intermediate itself was also prepared efficiently by simply changing the protective group.,10.1021/ol7029646,2008-01-26,0.6484856900258169
Journal of the American Chemical Society,11-Step Total Synthesis of Araiosamines,"A concise route to a small family of exotic marine alkaloids known as the araiosamines has been developed, and their absolute configuration has been assigned. The dense array of functionality, high polarity, and rich stereochemistry coupled with equilibrating topologies present an unusual challenge for chemical synthesis and an opportunity for innovation. Key steps involve the use of a new reagent for guanidine installation, a remarkably selective C-H functionalization, and a surprisingly simple final step that intersects a presumed biosynthetic intermediate. Synthetic araiosamines were shown to exhibit potency against Gram-positive and -negative bacteria despite a contrary report of no activity.",10.1021/jacs.6b09701,2016-10-17,0.6484765022302058
Synlett,An Enantioselective Formal Synthesis of (+)-Lactacystin from Hydroxymethyl Glutamic Acid (HMG),"A formal synthesis of (+)-lactacystin from hydroxymethylglutamic acid (HMG), with an alkylidene carbene insertion reaction being used to construct the key nitrogen-bearing quaternary centre has been completed. Our route intercepts that of Shibasaki at an advanced pyrrolidinone intermediate, from which the synthesis can be completed following Donohoe’s route.",10.1055/s-0029-1219207,2010-01-19,0.6484549807562476
Tetrahedron,"Synthetic route to neurotoxins in the 2,7--histrionicotoxin series",,10.1016/s0040-4039(00)91120-1,1975-01-01,0.6484146038679488
Organic Process Research & Development,Development of a Scalable Process for the Synthesis of Cyclopropyl-Methyl-Proline with Complex Stereochemistry: A Key Building Block of Factor D Inhibitors,"The development of a scalable process for a complex intermediate featuring a chiral, quaternary cyclopropane moiety presented significant challenges. We report two generations of synthetic strategies appropriate for the respective stages of development. The initial approach utilized a stereoselective Simmons–Smith cyclopropanation of ( R )-pyroglutamic acid ester, which predominantly yielded the undesired stereoisomer. To circumvent this issue, we implemented a strategy that combined isomerization, recycling of the undesired isomer, and selective crystallization to improve the yield of the desired product. An important insight was that the Simmons–Smith cyclopropanation exhibited opposite stereoselectivity with a benzoyl ester of a prolinol substrate, resulting in the desired stereoisomer as the major product. This understanding enabled the development of a second-generation process that facilitated the large-scale production of the targeted intermediate, thus supporting the advancement of clinical trials.",10.1021/acs.oprd.4c00223,2024-10-15,0.6483792997954876
Synthesis,"Synthesis of 3-Ethyl-4-methyl-1,5-dihydro-2H-pyrrol-2-one by Novel Palladium(II)-Catalyzed Cyclization and Ring-Closing Metathesis","Synthesis of 3-ethyl-4-methyl-1,5-dihydro-2 H -pyrrol-2-one is described starting from commercially available allylamine and 4-methoxybenzylamine employing palladium-catalyzed cyclization or ring-closing metathesis as the key steps.",10.1055/s-0034-1379985,2015-02-17,0.6483675378472864
Organic Letters,Convergent Total Synthesis of the Siderophore Piscibactin as Its Ga<sup>3+</sup> Complex,"The siderophore piscibactin is a key virulence factor involved in the iron uptake of pathogenic bacteria Photobacterium damselae subsp. piscicida and Vibrio anguillarum, responsible for the fish diseases photobacterioisis (pasteurellosis) and vibriosis, respectively. A convergent total synthesis of its Ga 3+ complex using l -/ d -cysteine as chiral agents and Meldrum’s acid is described. A Staudinger reduction/Aza-Wittig process in the synthesis of the acid-sensitive β-hydroxy-2,4-disubstituted thiazoline moiety and the convenient protecting groups was a key step in this synthesis.",10.1021/acs.orglett.0c03850,2020-12-23,0.648362717551454
Tetrahedron,An improved practical synthesis of protected α-amino selenocarboxylates and its application to the synthesis of N-(α-aminoacyl)sulfonamides,,10.1016/j.tetlet.2009.07.080,2009-07-19,0.6483289933702696
Organic Letters,Toward an Enantioselective Total Synthesis of Sarain A:  Construction of an Advanced Intermediate and Rearrangement of the Sarain A Core under Mild Conditions,A high-yielding N-sulfonyliminium ion-enoxysilane cyclization and a ring-closing metathesis are key steps in the enantioselective synthesis of late-stage intermediates en route to sarain A. Also revealed is an unprecedented rearrangement of the tetracyclic sarain A core under mildly acidic conditions. [structure: see text],10.1021/ol050038m,2005-02-01,0.6483259798147321
Tetrahedron,"Convergent synthesis of S-8921, a new potent hypocholesterolemic arylnaphthalene lignan analog",,10.1016/s0040-4039(98)02554-4,1999-02-01,0.6483257200214863
Green Chemistry,Efficient and sustainable transformation of gamma-valerolactone into nylon monomers,A route for efficient synthesis of bio-nylon monomers from gamma-valerolactone has been developed.,10.1039/c5gc01922b,2015-09-21,0.6483189065550053
Organic Letters,Asymmetric Total Synthesis of (+)-Shearilicine,"The asymmetric total synthesis of indoloditerpenoid shearilicine ( 1 ) has been reported. A late-stage Achmatowicz rearrangement facilitated the formation of pyran derivatives, followed by a final cyclization step that completed the synthesis of target indoloditerpenoid shearilicine ( 1 ). Importantly, the first total syntheses of epi -shearilicine ( 27 ), potential natural products, along with vinyl ether intermediate 26 have also been achieved in the ketal formation step.",10.1021/acs.orglett.5c02862,2025-08-13,0.6483098479712133
Organic Letters,Divergent Synthesis and Antigenicity Evaluation of Core Oligosaccharides of the Lipopolysaccharides from <i>Acinetobacter baumannii</i> SMAL and ATCC 19606,"Acinetobacter baumannii poses a serious threat to human health. Pathogenic bacterial lipopolysaccharides (LPSs) are potent immunogens for the development of antibacterial vaccines. To investigate the antigenic properties of A. baumannii LPS, five well-defined core oligosaccharide fragments from the LPS of A. baumannii SMAL and ATCC 19606 were synthesized. A divergent synthesis strategy based on orthogonally protected α-(2 → 5)-linked Kdo dimer 6 was developed. Selective exposure of different positions in this key precursor and then elongation of sugar chains via stereocontrolled formation of both 1,2- trans and 1,2- cis -2-aminoglycosidic linkages permitted the efficient synthesis of the targets. The synthetic route also highlights a 4- O and then 7- O glycosylation sequence for assembly of the novel 4,7-branched Kdo framework. Antigenicity assay using the glycan microarray technique disclosed that tetrasaccharide 3 featuring both 4,7-branch and α-(2 → 5)-Kdo-Kdo structural elements was a potential antigenic determinant.",10.1021/acs.orglett.4c02892,2024-09-16,0.6482833688344003
Journal of the American Chemical Society,"Concise, Asymmetric, Stereocontrolled Total Synthesis of Stephacidins A, B and Notoamide B","Concise asymmetric total syntheses of the fungal metabolites (-)-stephacidin A, (+)-stephacidin B, and (+)-notoamide B are described. Key features of these total syntheses include (1) a facile synthesis of (R)-allyl proline methyl ester, (2) a revised route toward the pyranoindole ring system, (3) a novel cross-metathesis strategy for the introduction of important functional groups, and (4) an SN2' cyclization to form the [2.2.2] bridged bicyclic ring system. Furthermore, our synthesis has taken advantage of microwave heating to shorten reaction times as well as increase yields for the preparation of vital intermediates.",10.1021/ja070259i,2007-04-25,0.6482788120268839
Journal of Organic Chemistry,Synthesis of (−)-7-Epiaustraline and (−)-1-Epicastanospermine,"Highly efficient and selective syntheses of the title compounds are described. The cornerstone of the synthetic plan is the tandem inter [4 + 2]/inter [3 + 2] cycloaddition process. These syntheses differ from previous applications of this strategy in that they incorporate an alkylation in the hydrogenolysis step to close the second ring of the azabicyclic systems. Notable features of the sequence are (1) the highly regio- and stereoselective [3 + 2] cycloaddition of nitronate 15 with siloxymethyl (Z)-beta-silylvinyl ketone (Z)-22b and (2) the highly selective reduction of the resulting ketone 24a with L-Selectride. A single-crystal X-ray structure analysis of synthetic (-)-7-epiaustraline confirmed that the targeted structure was successfully synthesized. This stimulated a reexamination of the structural assignment of the natural product. (-)-1-Epicastanospermine was synthesized in four steps from the common intermediate 27a. The absolute configuration of (-)-1-epicastanospermine was assured by single-crystal X-ray structure analysis of intermediate (-)-27a. Thus, the sign of the optical rotation had to be revised. The overall efficiency of these syntheses were 9 steps and 23% yield for (-)-7-epiaustraline and 10 steps and 20% yield for (-)-1-epicastanospermine",10.1021/jo991990d,2000-03-23,0.6482336744303698
Organic Letters,Stereoselective Synthesis of New Conformationally Restricted Analogues of a Potent CGRP Receptor Antagonist,"[structures: see text] A stereocontrolled racemic synthesis of conformationally restricted analogues 2a and 2b of a potent CGRP receptor antagonist 1 by novel functionalization of 2-substituted octahydropyrido[1,2-a]pyrazin-6-ones is described. The new diastereoselective LDA-promoted alpha-nitration of intermediate lactams established the required trans-configuration in the desired products.",10.1021/ol0510062,2005-05-17,0.6481859116545728
Organic Letters,Synthesis of Parvistemin A <i>via</i> Biomimetic Oxidative Dimerization,"The first synthesis of the naturally occurring benzoquinone dimer parvistemin A is reported. The key step is the late stage iron(III) mediated dimerization of a 1,2,4-trihydroxyarene to give the natural product in good yield, a phenol oxidative coupling that is believed to be biomimetic. The route proceeds in seven steps from an inexpensive commercially available acetophenone in 14% overall yield.",10.1021/ol201246e,2011-06-06,0.6481719441219334
European Journal of Organic Chemistry,A Scalable High‐Yielding and Selective Oxidative Heck Cross‐Coupling – A Key Step for the Synthesis of <i>trans‐</i>Stilbenes,"Abstract A selective oxidative Heck cross‐coupling method was developed and optimized as a pivotal step for a synthetic route leading to the trans‐ stilbene framework. The developed method and synthesis were needed in a SAR study in progress that concerned design and development of an inhibitor for the human cell xCT antiporter system. The developed oxidative Heck cross‐coupling method was examined with a variety of substrates and reagents to produce a library of different substituted trans‐ stilbenes, which revealed the method to hold a very good tolerance for an assortment of functional groups. The final synthetic route was successfully scaled‐up (from mg scale) and performed in a 150 g (&gt;1000×up‐scaled) batch run to obtain an overall yield of 73 % (over three steps), which corresponds to a mean step yield of 90 %. The inhibitor candidate DC10 [( E )‐5‐(2‐([1,1′‐biphenyl]‐4‐yl)vinyl)‐2‐hydroxy‐benzoic acid] was produced in multi‐gram quantities (≈33 g) that subsequently was forwarded for animal efficacy and toxicology studies. The scaled‐up process constitutes the first example of an oxidative Heck cross‐coupling on &gt;100‐gram scale.",10.1002/ejoc.202100493,2021-07-02,0.64815501256588
Organic Process Research & Development,"Development of a Process to a 4-Arylated 2-Methylisoquinolin-1(2<i>H</i>)-one for the Treatment of Solid Tumors: Lessons in Ortho-Bromination, Selective Solubility, Pd Deactivation, and Form Control","We here present an optimized, scalable synthesis of bromodomain and extra-terminal (BET) inhibitor BMS-986378 (CC-90010). The original route and process 1A was 7 steps with 33.8% yield and featured numerous problematic solvents, process safety concerns, difficult to scale unit operations, and challenging to control impurities. Reaction optimization to remove or mitigate these challenges resulted in our first scale-up route and process, 2A. Subsequent challenges encountered on scale-up of route and process 2A warranted the creation and implementation of an enhanced process, which eliminated dichloromethane from a phenol bromination, improved catalyst performance in the penultimate cross-coupling, and finally developed a concomitant solvent charging process for form control in the final API crystallization. The resulting scale-up route and process, 2B, was demonstrated on a >50 kg scale and afforded the final product in 49% yield over 7 steps in >99.9% assay and area purity, meeting all ICH requirements for quality.",10.1021/acs.oprd.2c00057,2022-04-20,0.6481498271682851
Journal of the American Chemical Society,Total Synthesis of the Novel Immunosuppressant Sanglifehrin A,"The total synthesis of the novel immunosuppressant sanglifehrin A (SFA, 1 ) is described. The approach is flexible, convergent, and stereoselective. The use of Paterson's aldol methodology was pivotal for the preparation of the novel, highly substituted spirolactam fragment of SFA. The 22-membered macrocyclic core of the molecule and the coupling of this fragment to the spirolactam moiety were successfully achieved using selective intra- and intermolecular Stille reactions, respectively. Carbodiimide-based protocols were employed for the synthesis of the tripeptide backbone.",10.1021/ja994285v,2000-04-01,0.6481366230552987
Synthesis,"Copper(I)-Catalyzed Intramolecular Caryl-O Bond-Forming Cyclization for the Synthesis of 1,4-Benzodioxines and Its Application in the Total Synthesis of Sweetening Isovanillins","Various substituted 1,4-benzodioxines were synthesized through an Ullmann-type intramolecular Caryl-O coupling cyclization reaction using a catalytic amount of BINOL-CuI complex. This methodology was successfully utilized as the key step in the total synthesis of isovanillyl sweetening agents 5-(2,3-dihydro-1,4-benzodioxin-2-yl)-2-methoxyphenol and 5-(2,3-dihydro-1,4-benz­oxathiin-2-yl)-2-methoxyphenol in 15.8% and 14.85% overall yields in five steps from isovanillin.",10.1055/s-0030-1258206,2010-08-13,0.6481244753123926
Organic Letters,Synthesis of Labdane Diterpenes Galanal A and B from (+)-Sclareolide,The first chemical synthesis of galanal A and B was achieved by a concise and highly efficient pathway starting from commercially available (+)-sclareolide and features a Wittig reaction and a titanocene-mediated radical cyclization as the key steps.,10.1021/ol501121v,2014-05-05,0.6481233520999155
Tetrahedron,"Simple regioselective synthesis of -7a-methylhydrind-4-en-1-one, a key intermediate for steroid total synthesis",,10.1016/s0040-4039(01)82029-3,1981-01-01,0.6481218998035183
Organic Letters,Stereodivergent Synthesis of 1-Hydroxymethylpyrrolizidine Alkaloids,"A first stereodivergent strategy for the asymmetric synthesis of all stereoisomers of 1-hydroxymethylpyrrolizidine alkaloids is developed using an asymmetric self-Mannich reaction as a key step. An anti-selective self-Mannich reaction of methyl 4-oxobutanoate with the PMP-amine catalyzed by a chiral secondary amine is successfully optimized for the asymmetric synthesis of (+)-isoretronecanol and (-)-isoretronecanol. A syn-selective self-Mannich reaction catalyzed by proline is utilized for the asymmetric synthesis of the diastereomer, (+)-laburnine, and its enantiomer, (-)-trachelanthamidine.",10.1021/acs.orglett.0c01375,2020-05-27,0.6481178074472279
Tetrahedron,Synthetic studies on Rabdosia diterpene lactones I: The preparation of a key tricyclic intermediate,,10.1016/s0040-4039(00)83918-0,1986-01-01,0.6481119147713335
Synthesis,Total Synthesis of (+)-Cladospolide A,A stereoselective total synthesis of (+)-cladospolide A from d -ribose is described. Key features of the synthesis include olefin cross metathesis and Yamaguchi lactonization.,10.1055/s-0031-1291154,2012-06-15,0.648032456288475
Synlett,Imino Glycals in Synthesis: Preparation of Novel Deoxymannojirimycin Analogues,All articles of this category The synthesis of imino glucal 2 from tetra- O -benzyl-d-glucopyranose in 7 steps is described. This imino sugar building block is converted into conformationally constrained deoxymannojirimycin analogue (+)- 9 by means of a stereocontrolled cyclopropanation followed by a two step deprotection sequence. Regioselective fission of the cyclopropane ring prior to deprotection provides access to related analogue (+)- 11 . carbohydrates - piperidines - stereoselective synthesis - imino glycals - glycosidases,10.1055/s-2001-16049,2001-01-01,0.6480289614427625
Journal of Organic Chemistry,Bi(OTf)<sub>3</sub>-Mediated Intramolecular Olefinic Cyclization: Synthesis of Substituted Aryl-Dihydronaphthalenes and Indenes,"In this article, a facile two-step and one-pot synthetic route for the preparation of substituted aryl dihydronaphthalenes starting from 2-allylbenzaldehydes via Grignard 1,2-addition and Bi(OTf) 3 -catalyzed intramolecular olefinic cyclization has been developed. A five-membered ring indene skeleton is also prepared via olefin isomerization, 1,2-addition followed by cyclization. Some key structures are determined using single-crystal X-ray crystallography. A possible mechanism is presented herein.",10.1021/acs.joc.7b01278,2017-06-15,0.6480206329186191
Angewandte Chemie International Edition,Scalable De Novo Synthesis of Aldgarose and Total Synthesis of Aldgamycin N,"Since the accompanying study had shown that the introduction of the eponymous aldgarose sugar to the C5-OH group of the macrocyclic aglycone of aldgamycin N is most difficult, if not even impossible, the synthesis route was revised and the glycosidation performed at an earlier stage. To mitigate the ""cost"" of this strategic amendment, a practical and scalable de novo synthesis of this branched octose was developed. The glycoside formation required mild conditions; it commenced with the reaction of the aglycone with the trichloroacetimidate donor to give a transient orthoester, which slowly rearranged to the desired aldgaropyranoside. The presence of the polar peripheral groups in the product did not impede the selective late-stage functionalization of the macrolide ring itself: the contained propargylic alcohol entity was readily transformed into the characteristic acyloin motif of the target by a ruthenium-catalyzed trans-hydrostannation followed by a modified Chan-Lam-type coupling.",10.1002/anie.202016477,2021-01-15,0.6480136034241452
Journal of the American Chemical Society,Total Synthesis of Phosphatidylinositol Mannosides of <i>Mycobacterium tuberculosis</i>,"The total synthesis of phosphatidylinositol mannosides (PIMs), a key class of antigenic glycolipids found on the cell wall of Mycobacterium tuberculosis, is described. The synthetic strategy relied on a [4 + 3] glycosylation of tetramannoside 1 and pseudotrisaccharide 2, which allowed for convergent access to the glycan backbone of the phosphatidylinositol dimannoside (PIM2) and hexamannoside (PIM6). A short practical synthesis of tuberculostearic acid was achieved based on a copper-catalyzed cross-coupling reaction. Union of the glycan and lipid parts resulted in the first total synthesis of native PIM2 and PIM6.",10.1021/ja0565368,2006-02-24,0.6480075146239345
Organic Process Research & Development,"Development of an Efficient and Scalable Biocatalytic Route to (1<i>S</i>,4<i>R</i>)-8-Hydroxy-1,2,3,4- tetrahydro-1,4-methanonaphthalen-5-yl Propionate via Enantioselective Enzymatic Desymmetrization of a Prochiral Diester","An efficient procedure for enzymatic desymmetrization of the prochiral diphenol compound 2 was successfully developed to prepare the pharmaceutical intermediate (1 S,4 R )-8-hydroxy-1,2,3,4-tetrahydro-1,4-methanonaphthalen-5-yl propionate with 99.0% purity and 97.82% ee in 81.59% overall yield. The enzymatic reaction was scalable and cost-effective and avoided the process of crystallization-induced resolution in the reported synthetic strategy for yimitasvir ( 1 ), thus helping to increase utilization of the chiral motif.",10.1021/acs.oprd.9b00188,2019-05-13,0.6480067756112798
Tetrahedron,Synthesis of the right half of mycalamide A. A formal total synthesis,,10.1016/0040-4039(94)88289-4,1994-10-01,0.6479822719451258
Tetrahedron,Total synthesis of (+)-pederin. 1. Stereocontrolled synthesis of (+)-benzoylpedamide,,10.1016/s0040-4039(00)99027-0,1985-01-01,0.6479822719451258
Tetrahedron,Total synthesis of ma'edamines E and F via Chichibabin pyridinium synthesis,,10.1016/j.tetlet.2025.155762,2025-07-29,0.6479822719451258
Tetrahedron,"Total synthesis of serratomolide I. Synthesis of o,o'-diacetylserratamolide",,10.1016/s0040-4039(01)89321-7,1964-01-01,0.6479822719451258
Tetrahedron,Synthesis of the C15–C27 portion of venturicidins: a formal total synthesis of venturicidin X,,10.1016/s0040-4039(01)00518-4,2001-05-01,0.6479822719451258
Tetrahedron,"Regiospecific synthesis of 1,4,5-trioxygenated anthraquinones. A total synthesis of islandicin",,10.1016/s0040-4039(01)96286-0,1973-01-01,0.6479822719451258
Tetrahedron,"Synthesis of 12a-deoxy-5a,6-anhydrotetracycline. The first total synthesis of the naturally occuring tetracycline",,10.1016/s0040-4039(00)90501-x,1967-01-01,0.6479822719451258
Tetrahedron,The total synthesis of pamamycin 607. 1. Synthesis of a C1′-C11′ synthon,,10.1016/0040-4039(96)00638-7,1996-05-01,0.6479822719451258
Tetrahedron,Towards the total synthesis of phorboxazoles A and B: Stereocontrolled synthesis of a C20C32 subunit,,10.1016/s0040-4039(98)01539-1,1998-09-01,0.6479822719451258
Tetrahedron,Furans in synthesis.7. A formal total synthesis of (+/−)-perhydrohistrionicotoxin,,10.1016/s0040-4039(00)95450-9,1987-01-01,0.6479822719451258
Tetrahedron,Total synthesis of (+)-blastmycinone and formal synthesis of (+)-antimycin A3b,,10.1016/j.tetlet.2006.12.088,2007-01-09,0.6479822719451258
Tetrahedron,"Total synthesis of the didemnins - 2. Synthesis of didemnin A, B, C and prolyldidemnin A",,10.1016/s0040-4039(00)80507-9,1988-01-01,0.6479822719451258
Tetrahedron,Total synthesis of the aglycone of venturicidins A and B — I synthesis of C1C14 segment,,10.1016/s0040-4039(00)88866-8,1990-01-01,0.6479822719451258
Journal of Organic Chemistry,Construction of an Advanced Tetracyclic Intermediate for Total Synthesis of the Marine Alkaloid Sarain A,"In work directed toward a total synthesis of the marine alkaloid sarain A (1), the advanced intermediate 54, containing all the key elements and the seven stereogenic centers of sarain A, has been successfully synthesized from bicyclic lactam 4, previously prepared via an intramolecular stereospecific [3 + 2]-azomethine ylide dipolar cycloaddition. Intermediate lactam 4 could be efficiently converted to N-Boc derivative 12. Introduction of a two-carbon fragment into lactam 12 which eventually becomes the C-7',8' syn diol of the ""eastern"" ring was then achieved by C-acylation of the corresponding enolate with methoxyacetyl chloride followed by a highly stereoselective ketone reduction with Zn(BH4)2 to afford alcohol 16. Intermediate 16 has the incorrect C-7' relative stereochemistry for sarain A, but this problem was conveniently remedied by inverting the C-7' center via an intramolecular Ohfune-type cyclization of the silyl carbamate derived from Boc mesylate 27 to produce the key cyclic carbamate 28. It was then possible to convert acetal 28 to allylsilane 32 followed by cyclization to the alkaloid tricyclic core 33 via an allylsilane/N-sulfonyliminium ion cyclization. Formation of the ""western"" macrocyclic ring has been successfully addressed using functional group handles at C-3' and N-1' on the tricyclic core via a ring-closing olefin metathesis (RCM) strategy with the second-generation Grubbs ruthenium catalyst to produce intermediate macrolactam 47. A chelation-controlled addition of ethynylmagnesium bromide to advanced aldehyde 51 afforded a single diastereomeric adduct 53 which is tentatively assigned to have the correct C-7',8' syn-diol stereochemistry. This adduct could be rearranged to the conveniently protected amino carbonate 54 which is set up for construction of the remainder of the eastern ring of sarain A.",10.1021/jo052504r,2006-01-31,0.647981952848212
Organic Letters,A Concise Route to (+)-Estrone,"A concise route to the Torgov diene, the key intermediate of estrone, has been devised using a chiral dioxycyclopentenone as the starting material by employing a sequence of five steps of reactions involving a Lewis acid-mediated Diels-Alder reaction with Dane's diene.",10.1021/ol005988g,2000-06-01,0.6479616512343069
Organic Letters,Synthesis of (+)-Casuarine,"[formula: see text] The first synthesis of (+)-casuarine, a pentahydroxy pyrrolizidine alkaloid, is described. The key bond-forming events occur in a tandem [4 + 2]/[3 + 2] nitroalkene cycloaddition involving nitroalkene 6, chiral vinyl ether 7b, and vinyl silane 4. This process also creates five of the six stereocenters present in this potent glycosidase inhibitor. Completion of the synthesis required only four additional steps and delivered (+)-casuarine in 20% overall yield.",10.1021/ol9909886,1999-09-23,0.6479579934059615
Journal of Organic Chemistry,A New Route to Aristocularine Alkaloids:  Total Synthesis of Aristoyagonine,"A short and efficient synthesis of aristocularines, involving the sequential construction of phosphorylated 4-alkoxyisoindolinones, Horner-type reaction, and ultimate cyclization by diaryl ether coupling, is disclosed. The success of this new conceptual approach is demonstrated by the total synthesis of the aristocularine alkaloid aristoyagonine.",10.1021/jo049869g,2004-05-28,0.647957379500351
Journal of Organic Chemistry,(−)-15-Deoxyspergualin: A New and Efficient Enantioselective Synthesis Which Allows the Definitive Assignment of the Absolute Configuration,"(±)-15-Deoxyspergualin (DSG) has recently been marketed in Japan for the control of corticoresistant acute renal graft rejection. A nine-step total synthesis of its eutomer ((−)-DSG) 2 has been developed starting from 7-bromoheptanenitrile 3 and N 1, N 4 -bis(benzyloxycarbonyl)spermidine. The use of a chiral α-alkylbenzyl group to protect the hydroxyl of the α-hydroxyglycine moiety allowed its chromatographic resolution and afforded a practical access to 2 with a high optical purity and a 7% overall yield. Moreover, X-ray structure analysis of the key crystalline intermediate 7b definitely confirmed the previously proposed absolute configuration of 2 .",10.1021/jo9811118,1998-12-01,0.6479502943097192
Journal of the American Chemical Society,Protecting Group-Free Total Synthesis of (−)-Lannotinidine B,"The first total synthesis of (-)-lannotinidine B, a unique tetracyclic constitutent of Lycopodium annotinum, has been accomplished in 10 steps with 23% overall yield. The completed short and efficient synthesis is characterized with three highly chemo- and/or stereoselective reductive-amination steps to furnish the desired trans-fused 6/6 bicycle and the aza seven-membered ring system, and a direct intramolecular acyloin condensation to deliver the cyclopentanone moiety, as well as successful application of a protecting group-free strategy and an optimal redox order.",10.1021/ja305261h,2012-07-16,0.6479307945896169
Organic Letters,Total Synthesis of (+)-Raputindole A: An Iridium-Catalyzed Cyclization Approach,"High Resolution Image Download MS PowerPoint Slide This work describes the total synthesis of raputindole A ( 1 ) through a convergent approach that features (1) an iridium-catalyzed cyclization to assemble the tricyclic core of the northern part, (2) enzymatic resolution to secure the preparation of an enantiomerically pure benzylic alcohol intermediate, and (3) the installation of the isobutenyl side chain via methallylation of the corresponding benzylic carbocation and coupling of the northern and southern parts via the Heck reaction. (+)-Raputindole A ( 1 ) was prepared in 10 steps (longest linear sequence) in 3.3% overall yield.",10.1021/acs.orglett.0c01943,2020-08-05,0.6479291011905535
Journal of Organic Chemistry,"Asymmetric Synthesis of Both Enantiomers of <i>a</i><i>nti</i>-4,4,4-Trifluorothreonine and 2-Amino-4,4,4-trifluorobutanoic Acid","A short and efficient enantioselective synthesis of both enantiomers of anti-4,4,4-trifluorothreonine and 2-amino-4,4,4-trifluorobutanoic acid was successfully developed. Trifluoromethylation of benzyl-protected bromoalkene 4 provided key intermediate trifluoromethylated trans-disubstituted alkene 2 in good yield. The sequence then involved Sharpless asymmetric dihydroxylation, nucleophilic opening of cyclic sulfate with NaN(3), palladium-catalyzed selective hydrogenation, and oxidation.",10.1021/jo0344384,2003-08-22,0.6479240376417834
Organic Process Research & Development,"A Scalable, Enantioselective Synthesis of the α<sub>2</sub>-Adrenergic Agonist, Lofexidine","A scalable and high-yielding synthetic route toward pure enantiomers of the α 2 -adrenergic agonist, lofexidine hydrochloride, is presented. Salient features include a rapid one-pot amide alkylation-imidazoline formation sequence on the carboxamide function of α-(2,6-dichlorophenoxy)propionamide, while preserving the sensitive configuration about the α-carbon of the resulting product. A means to accelerate the sluggish O -alkylation of the carboxamide function of α-(2,6-dichlorophenoxy)propionamide by Me 3 O + BF 4 − is also described, which may be of general applicability.",10.1021/op8002689,2009-01-08,0.6479239671413379
Organic Letters,"Synthesis of 1,2-<i>cis</i>-Homoiminosugars Derived from GlcNAc and GalNAc Exploiting a β-Amino Alcohol Skeletal Rearrangement","The synthesis of 1,2-cis-homoiminosugars bearing an NHAc group at the C-2 position is described. The key step to prepare these α-D-GlcNAc and α-D-GalNAc mimics utilizes a β-amino alcohol skeletal rearrangement applied to an azepane precursor. This strategy also allows access to naturally occurring α-HGJ and α-HNJ. The α-D-GlcNAc-configured iminosugar was coupled to a glucoside acceptor to yield a novel pseudodisaccharide. Preliminary glycosidase inhibition evaluation indicates that the α-D-GalNAc-configured homoiminosugar is a potent and selective α-N-acetylgalactosaminidase inhibitor.",10.1021/ol502926f,2014-10-20,0.647921038970883
Organic Letters,Total Synthesis of (+)-Gregatin B and E,"The first total synthesis of (+)-gregatin E and a new total synthesis of (+)-gregatin B are described. Key features of our synthetic approach involve a palladium-catalyzed cyclization-methoxycarbonylation of optically active propargylic acetate and a Suzuki-Miyaura coupling or CuTC-mediated coupling reaction. The absolute configuration of (+)-gregatin E (5R,5'S) is proposed.",10.1021/ol402472q,2013-09-25,0.6479080777116164
Organic Letters,"Enantioselective Synthesis of (−)-Jiadifenin, a Potent Neurotrophic Modulator","The first enantioselective synthesis of (-)-jiadifenin (1), a potent neurite outgrowth promoter isolated from the Illicium species, is described. The synthetic strategy builds upon bicyclic motif 6, which represents the AB ring of the natural product and proceeds in 19 steps and 1.1% overall yield. Key to our approach is a Mn(III)-mediated oxidation reaction of A ring that, following a regio- and diastereoselective α-hydroxylation and methylation sequence, produces the desired functionalities of (-)-jiadifenin. The effect of synthetic 1 in NGF-mediated neurite outgrowth was also measured in PC-12 cells.",10.1021/ol201742j,2011-08-03,0.6479058828672384
Journal of Organic Chemistry,A Concise Synthesis of Castanospermine by the Use of a Transannular Cyclization,"A nine-step synthesis of (+)-castanospermine has been accomplished in 22% overall yield from methyl alpha-D-glucopyranoside. The key transformations involve a zinc-mediated fragmentation of benzyl-protected methyl 6-iodoglucopyranoside, ring-closing olefin metathesis, and strain-release transannular cyclization to afford the indolizidine skeleton of the natural product.",10.1021/jo9019495,2009-10-26,0.6478946357590152
Journal of Organic Chemistry,"A General Strategy for the Diastereoselective Synthesis of 2,6-Diaryl-3,7-dioxabicyclo[3.3.0]octane Lignans","A strategy for the stereoselective synthesis of all the possible diastereoisomers of the 2,6-diaryl-3,7-dioxabicyclo[3.3.0]octane (furofuran) lignans from a single dihydrofuran precursor is described. The key steps involve a diastereocontrolled templated cationic cyclization followed by stereoselective reduction of the resulting methyl glycoside.",10.1021/jo035148q,2003-10-24,0.6478885860475261
Organic Letters,A Route to Polyprenol Pyrophosphate-Based Probes of <i>O</i>-Polysaccharide Biosynthesis in <i>Klebsiella pneumoniae</i> O2a,"An approach for the assembly of polyprenol pyrophosphate-based probes of O-polysaccharide biosynthesis in Klebsiella pneumoniae serotype O2a is described. This convergent route features high-yielding, diastereoselective glycosylations and the late-stage installation of the polyprenol pyrophosphate moiety. Although applied to the synthesis of a nonasaccharide bearing a farnesyl group (1), the modular nature of the route makes it amenable to the synthesis of additional derivatives containing either larger glycans or different lipid domains.",10.1021/acs.orglett.8b04093,2019-01-25,0.6478788516841554
Journal of the American Chemical Society,Streamlined Total Synthesis of Uncialamycin and Its Application to the Synthesis of Designed Analogues for Biological Investigations,"From the enediyne class of antitumor antibiotics, uncialamycin is among the rarest and most potent, yet one of the structurally simpler, making it attractive for chemical synthesis and potential applications in biology and medicine. In this article we describe a streamlined and practical enantioselective total synthesis of uncialamycin that is amenable to the synthesis of novel analogues and renders the natural product readily available for biological and drug development studies. Starting from hydroxy- or methoxyisatin, the synthesis features a Noyori enantioselective reduction, a Yamaguchi acetylide-pyridinium coupling, a stereoselective acetylide-aldehyde cyclization, and a newly developed annulation reaction that allows efficient coupling of a cyanophthalide and a p-methoxy semiquinone aminal to forge the anthraquinone moiety of the molecule. Overall, the developed streamlined synthesis proceeds in 22 linear steps (14 chromatographic separations) and 11% overall yield. The developed synthetic strategies and technologies were applied to the synthesis of a series of designed uncialamycin analogues equipped with suitable functional groups for conjugation to antibodies and other delivery systems. Biological evaluation of a select number of these analogues led to the identification of compounds with low picomolar potencies against certain cancer cell lines. These compounds and others like them may serve as powerful payloads for the development of antibody drug conjugates (ADCs) intended for personalized targeted cancer therapy.",10.1021/jacs.6b04339,2016-06-07,0.6478528539369438
Organic Process Research & Development,"New Scalable Synthetic Routes to <b>ELQ-300</b>, <b>ELQ-316</b>, and Other Antiparasitic Quinolones","The endochin-like quinolone (ELQ) compound class may yield effective, safe treatments for a range of important human and animal afflictions. However, to access the public health potential of this compound series, a synthetic route needed to be devised, which would lower costs and be amenable to large-scale production. In the new synthetic route described here, a substituted β-keto ester, formed by an Ullmann reaction and subsequent acylation, is reacted with an aniline via a Conrad–Limpach reaction to produce 3-substituted 4(1 H )-quinolones such as ELQ-300 and ELQ-316 . This synthetic route, the first described to be truly amenable to industrial-scale production, is relatively short (five reaction steps), does not require palladium, chromatographic separation, or protecting group chemistry, and may be performed without high vacuum distillation.",10.1021/acs.oprd.1c00099,2021-08-04,0.6478445975385512
Journal of Organic Chemistry,General Synthesis of 8-Aryl-2-tetralones,"Two alternative routes are described for the synthesis of 8-aryl-2-tetralones (1). Route A starts from alpha-tetralone 3 and involves 3 or 4 steps, with the selective Na-EtOH reduction of 1-aryl-7-methoxynaphthalenes 2 being the key step. The exclusive reduction of the A ring of naphthalenes 2 occurs when the aryl group at C-1 has no substituent at the ortho positions, affording tetrahydronaphthalenes 11. Reduction of the B ring of 2 becomes the major process when the aryl fragment has two substituents at the ortho positions, affording 8-aryl-2-tetralones 1 as the major component. Route B involves 5 steps starting from 2-tetralone 5, with the key step being the Suzuki coupling with triflate 4. This approach allows the synthesis of 8-aryl-2-tetralones 1 with no substituent at the ortho positions of the aryl fragment and with naphthalene and anthracene rings at C-8.",10.1021/jo060688j,2006-05-26,0.6478063233720357
Journal of Organic Chemistry,Synthesis of Neplanocin A and Its 3′-Epimer via an Intramolecular Baylis–Hillman Reaction,The key cyclopentenyl intermediate 11b was synthesized in 4 steps from d-ribose in 41% overall yield via an efficient intramolecular Baylis-Hillman reaction. This novel key intermediate can be modified easily and transformed to neplanocin A (1a) and its 3'-epimer (1b).,10.1021/jo501248e,2014-08-14,0.6477776484454602
Angewandte Chemie International Edition,Total Synthesis of (−)‐Daphenylline,"Abstract A concise and highly stereoselective total synthesis of the Daphniphyllum alkaloids (−)‐daphenylline has been accomplished. The synthesis was started from ( S )‐carvone and proceeded via a stereoselective Mg(ClO 4 ) 2 ‐catalyzed intramolecular amide addition cyclization, an intramolecular Diels–Alder reaction to construct the ABCD tetracyclic core architecture, and a Robinson annulation coupled with an oxidative aromatization sequence. Finally, the DF ring system was installed through an intramolecular Friedel–Crafts cyclization. The total synthesis of (−)‐daphenylline is achieved in 19 steps in the longest reaction sequence and in 7.6 % overall yield.",10.1002/anie.201902268,2019-03-27,0.6477712921450749
Angewandte Chemie International Edition,"Variable Synthesis of the Optically Active Thiotetronic Acid Antibiotics Thiolactomycin, Thiotetromycin, and 834‐B1","In seven steps: The antibiotic (+)-thiolactomycin was synthesized in seven steps and with 16 % overall yield from 4-acetoxy-2-methyl-2-buten-1-al, an intermediate of the industrial synthesis of vitamin A. Key transformations were the catalytic asymmetric Sharpless epoxidation of an ethoxycarbonyl-substituted pentadienol (93 % ee) and a regio- and stereoselective thiolysis of the resulting epoxide (see scheme).",10.1002/anie.200603562,2006-12-20,0.6477433305195807
Journal of the American Chemical Society,The Total Synthesis of (−)-Scabrolide A,"The first total synthesis of the norcembranoid diterpenoid scabrolide A is disclosed. The route begins with the synthesis of two chiral pool-derived fragments, which undergo a convergent coupling to expediently introduce all 19 carbon atoms of the natural product. An intramolecular Diels-Alder reaction and an enone-olefin cycloaddition/fragmentation sequence are then employed to construct the fused [5-6-7] linear carbocyclic core of the molecule and complete the total synthesis.",10.1021/jacs.0c02513,2020-03-30,0.647711270780889
Tetrahedron,Convergent synthesis of leukotriene a methyl ester,,10.1016/s0040-4039(01)83931-9,1980-01-01,0.6476888927534539
Journal of Organic Chemistry,Total Synthesis of Guanacastepene A: A Route to Enantiomeric Control,"[reaction: see text] The goal of the total synthesis of guanacastepene A served as a focus to bring together several chemical inquiries. One involved the synthesis of fused 5,7-hydrazulenones (see structure 20). Another issue had to do with the mechanistic intermediates in reductive cyclizations (see 17 to 18 and 19). The total synthesis required a mastery of an intramolecular Knoevenagel condensation of a beta,gamma-unsaturated ketone (see compound 41). Actually, cyclization was best accomplished when the terminal double bond of 41 was first converted to an epoxide. Further issues related to the stereochemistry at C5 and, rather surprisingly, the propensity for beta-face acetoxylation at C13. Crystallographic verification of the assigned beta-stereochemistry at C13 is provided. Finally, a route to optically active material is provided (see compound 20). A key element in this construction was an enantioselective addition of isopropenyl cuprate to 2-methylcyclopentenone (see compound 99).",10.1021/jo051470k,2005-09-20,0.647673801172471
Synlett,"Stereocontrolled Synthesis of a Trihydroxylated Indolizidine Alkaloid, 1-Deoxycastanospermine","All articles of this category An efficient and novel process is described for the asymmetric synthesis of (6 S ,7 R ,8 R ,8 aR )-6,7,8-trihydroxyindolizidine alkaloid, 1-deoxycastanospermine in 22% overall yield based on the C 2 -imide featuring the completely stereoselective reduction of an α-hydroxypyrrolidine intermediate elaborated through asymmetric deoxygenation of a quaternary α-hydroxylactam. indolizidine alkaloid - 1-deoxycastanospermine - deoxygenation - α-hydroxypyrrolidine - C 2 -imide",10.1055/s-1997-962,1997-08-01,0.647655638666458
Journal of Organic Chemistry,"Two Asymmetric Syntheses of AMG 221, an Inhibitor of 11β-Hydroxysteroid Dehydrogenase Type 1","Two asymmetric syntheses of AMG 221 (2), an inhibitor of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) discovered in our laboratories, are reported. One of the syntheses utilizes chiral trimethylsilyl cyanohydrin 12 as starting material and the other utilizes its enantiomer ent-12. The displacement approach involves the conversion of 12 to 2 via a six-step sequence, occurs with net inversion of configuration, and employs amine 6 as starting material. This route features a novel approach toward chiral dialkylsubstituted alpha-mercaptoacids. The cyclization approach entails the synthesis of 2 from ent-12 in 2 steps, takes place with net retention of configuration, and uses thiourea 8 as starting material. The final step of this route exemplifies a novel synthesis of chiral C-5 dialkylsubstituted 2-aminothiazolones from chiral alpha-hydroxyacids and thioureas. Insights into the mechanism of this transformation and study of the effect of the medium on the stereochemical outcome of the reaction are presented.",10.1021/jo900287b,2009-04-24,0.6476513356716948
Organic Letters,"Total Synthesis of Cyclic Tetrapeptide FR235222, a Potent Immunosuppressant that Inhibits Mammalian Histone Deacetylases","[structure: see text] The total synthesis of FR235222, a potent immunosuppressant with in vivo activities, has been achieved. The key steps include assembling its (2S,9R)-2-amino-9-hydroxy-8-oxodecanoic acid residue via an olefin cross-metathesis of a methyl (R)-lactate-derived homoallyl ketone with protected allyl amino acid and constructing its trans-(2R,4S)-4-methylproline unit from protected (R)-pyroglutamic acid in seven steps.",10.1021/ol050991r,2005-05-25,0.6476460234324872
Angewandte Chemie International Edition,Concise Total Synthesis of Dehaloperophoramidine,"Perophoramidine, dehaloperophoramidine, and communesin F are structurally related alkaloids having intriguing polycyclic structures. A strategy for the synthesis of dehaloperophoramidine has been developed. In this synthesis all skeletal atoms and all functional groups required to reach the target molecule are incorporated early in the sequence. This approach led to the discovery of two novel substrate-specific domino processes, one encompassing four steps and the other comprising five steps, thus resulting in an eight-step synthesis of dehaloperophoramidine.",10.1002/anie.201510661,2015-12-16,0.6475929106780504
Journal of Organic Chemistry,"Synthesis of an Anti-hepatitis B Agent, 2′-Fluoro-6′-methylene-carbocyclic Adenosine (FMCA) and Its Phosphoramidate (FMCAP)","2'-Fluoro-6'-methylene-carbocyclic adenosine (FMCA, 12) and its phosphoramidate prodrug (FMCAP, 14) have been proven as a potential anti-HBV agent against both adefovir-resistant as well as lamivudine-resistant double (rtL180M/rtM204V) mutants. Furthermore, in vitro, these agents have demonstrated significant activity against lamivudine/entecavir triple mutants (L180M + S202G + M204V). These preliminary results encourage us for further biological evaluation of FMCA and FMCAP to develop as a potential clinical candidate as an anti-HBV agent, which may overcome the problem of drug resistance in HBV therapy. To support the preclinical exploration, a scalable synthesis of this molecule was needed. In this communication, a practical and scalable synthesis of FMCA, and its prodrug, is reported via ketone 1. The selective opening of the isopropylidene group of 2 led to compound 3. Protection of the allylic hydroxyl group of 3, followed by fluorination and deprotection, afforded the key intermediate 10, which was condensed with a Boc-protected adenine, followed by deprotection, furnished the target nucleoside FMCA (12) in high yield. Further coupling of phosphorochloridate of L-alanine isopropyl ester (13) with FMCA gave its phosphoramidate prodrug FMCAP (14) in good yield.",10.1021/acs.joc.8b02599,2018-12-27,0.6475928105369843
Journal of the American Chemical Society,Asymmetric Total Synthesis of Hetidine-Type C<sub>20</sub>-Diterpenoid Alkaloids: (+)-Talassimidine and (+)-Talassamine,"Here, we report the first asymmetric total synthesis of (+)-talassimidine and (+)-talassamine, two hetidine-type C 20 -diterpenoid alkaloids. A highly regio- and diastereoselective 1,3-dipolar cycloaddition of an azomethine ylide yielded a chiral tetracyclic intermediate in high enantiopurity, thus providing the structural basis for asymmetric assembly of the hexacyclic hetidine skeleton. In this key step, the introduction of a single chiral center induces four new continuous chiral centers. Another key transformation is the dearomative cyclopropanation of the benzene ring and subsequent S N 2-like ring opening of the resultant cyclopropane ring with water as a nucleophile, which not only establishes the B ring but also precisely installs the difficult-to-achieve equatorial C7–OH group.",10.1021/jacs.1c01865,2021-05-03,0.6475420126889885
Journal of Organic Chemistry,A Short and Practical Synthesis of Oseltamivir Phosphate (Tamiflu) from (−)-Shikimic Acid,"Oseltamivir phosphate (1) was synthesized from (-)-shikimic acid through a short and practical synthetic route via eight steps in 47% overall yield. In addition, the highly regioselective and stereoselective nucleophilic replacement of OMs by the N(3) group in the third and seventh steps has been studied in detail, and the reaction conditions were optimized.",10.1021/jo900218k,2009-04-14,0.6475350458689223
Organic Letters,"Synthesis of (±)-Epoxysorbicillinol Using a Novel Cyclohexa-2,5-dienone with Synthetic Applications to Other Sorbicillin Derivatives","A novel route to epoxysorbicillinol as well as dimers of sorbicillin is reported. The synthesis is-in principle-amenable to enantioselectivity. The key step is an oxidative dearomatization to produce a stable and highly malleable p-quinol intermediate, which undergoes a highly diastereoselective epoxidation.",10.1021/ol0155438,2001-02-22,0.6475078134514114
Journal of Organic Chemistry,"Biomimetic Total Synthesis of Meiogynin A, an Inhibitor of Bcl-xL and Bak Interaction","A short, convergent, and selective synthesis of meiogynin A, an inhibitor of the antiapoptotic protein Bcl-xL, has been performed. This synthesis, based on a biomimetic approach, allowed the determination of its absolute configuration. Three isomers of meiogynin A have also been elaborated. One of these was found to be three times more potent than the natural compound.",10.1021/jo101088h,2010-10-07,0.6474964072522427
Organic Letters,Total Synthesis of Syringolin A,"A convergent, efficient synthesis of syringolin A has been accomplished in 13 steps from commercially available materials, Garner's aldehyde and L-valine. The unnatural 3,4-dehydrolysine fragment was prepared using successive Johnson-Claisen/Curtius rearrangement reactions. The macrolactamization and late-stage introduction of the side chain will provide convenient access to analogues of this promising proteasome inhibitor.",10.1021/ol101252y,2010-07-02,0.6474879900685542
Organic Letters,The Enantioselective Total Synthesis of (+)-3-Ketobrassicicene W and (−)-Alterbrassicicene B,"Herein the first enantioselective total synthesis of the C16- nor -fusicoccane diterpenoids (+)-3-ketobrassicicene W and (−)-alterbrassicicene B is described. The strategy evolved from our recent synthesis of (+)-alterbrassicicene C and leveraged the convergent union of two enantioenriched cyclopentene fragments. Substrate controlled stereoselectivity guided the route through hydration, oxidation and reduction steps to deliver (+)-3-ketobrassicicene W which was converted to (−)-alterbrassicicene B upon Lewis acid induced transannular oxa -Michael addition.",10.1021/acs.orglett.5c02336,2025-07-18,0.6474680345393083
Journal of Organic Chemistry,"Regioselective Synthesis of 4- and 7-Alkoxyindoles from 2,3-Dihalophenols:  Application to the Preparation of Indole Inhibitors of Phospholipase A<sub>2</sub>","An efficient and regioselective synthesis of 4- and 7-alkoxyindoles has been developed from commercially available starting materials such as 3-halophenols and 3-chloroanisole. Directed ortho-metalation followed by two palladium-catalyzed processes, a Sonogashira coupling and a tandem amination/cyclization reaction, allows the synthesis of regiochemically pure 4- and 7-substituted indoles. This strategy has been successfully applied to the preparation of 2-[3-(2-amino-2-oxoacetyl)-1-benzyl-2-ethyl-1H-indol-4-yloxy]acetic acid (LY315920), a known inhibitor of phospholipase A2.",10.1021/jo070643y,2007-06-09,0.6474391602470748
Organic Letters,The Formal Total Synthesis of (±)-Strychnine via a Cobalt-Mediated [2 + 2 + 2]Cycloaddition,"A short, highly convergent total synthesis of racemic isostrychnine, and thus strychnine, has been completed. The route involves 14 steps in the longest linear sequence and is highlighted by a cobalt-mediated [2 + 2 + 2]cycloaddition of an alkynylindole nucleus to acetylene.",10.1021/ol006131m,2000-07-08,0.6474115199104817
Tetrahedron,New and efficient enantiospecific synthesis of (−)-Methyl 5-epi-shikimate and methyl 5-epi-quinate from (−)-quinic acid,,10.1016/s0040-4039(97)01109-x,1997-07-01,0.647396609418454
Journal of the American Chemical Society,Asymmetric Total Synthesis of (−)-Amphidinolide V through Effective Combinations of Catalytic Transformations,"An asymmetric total synthesis of (-)-amphidinolide V was accomplished. The synthesis features a base-catalyzed alkynyl silane alcoholysis/ring-closing enyne metathesis sequence for facile construction of a 1,3-diene motif. A diene RCM followed by a ring-contractive allylic transposition of cyclic silyl ethers was incorporated for the stereoselective installation of a functionalized 1,5-diene subunit. An efficient proline-mediated direct cross-aldol condensation of two advanced aldehyde intermediates was utilized for the construction of a key α,β-unsaturated epoxyaldehyde. This total synthesis demonstrates the prowess of metal-catalyzed transformations in complex molecule synthesis.",10.1021/ja401717b,2013-03-21,0.6473865687815432
Tetrahedron,Synthesis of new chiral monodentate phosphines and their use in asymmetric hydrogenation,,10.1016/s0040-4039(02)00943-7,2002-07-01,0.6473860397006413
European Journal of Organic Chemistry,Total Synthesis and Glycosidase Inhibition Studies of (–)‐Gabosine J and Its Derivatives,"Abstract The total syntheses of (–)‐gabosine J and its two gabosinol derivatives, the reduced forms of (–)‐gabosine J, were achieved by a chiral pool strategy that started from inexpensive and readily available D ‐mannitol. The desymmetrization of the C 2 ‐symmetric tri‐ O ‐isopropylidene mannitol through a H 2 SO 4 /silica mediated hydrolysis of one of the two terminal ketals and a ring‐closing methathesis (RCM) of the appropriately protected diene are the key steps in these syntheses. The preparation of (–)‐gabosine J, which involved simple steps as well as inexpensive and readily available reagents and starting material, was completed in 14 steps with an overall yield of 13 %. Similarly, gabosinol J‐α and gabosinol J‐β (two synthetic derivatives of gabosine J) were prepared in 13 steps in an overall yield of 11 and 6 %, respectively. A preliminary investigation into the biological activity of these compounds revealed that (–)‐gabosine J inhibits α‐mannosidase with an IC 50 of 260 μ M . Its reduced form gabosinol J‐α inhibits β‐galactosidase with an IC 50 of 600 μ M , and gabosinol J‐β inhibits β‐glucosidase. This is the first synthesis of a gabosine that employs mannitol as the starting material and the first report of the biological activity of gabosine J.",10.1002/ejoc.201301782,2014-02-06,0.6473561070840027
Organic Letters,Asymmetric Total Synthesis of Senepodine F,"The first asymmetric total synthesis of the Lycopodium alkaloid senepodine F, which contains a decahydroquinoline ring ( AB -ring) and a quinolizidine ring ( CD -ring) connected by a methylene tether, has been achieved. The key steps of this synthesis include an organocatalytic asymmetric Diels–Alder reaction, a diastereoselective intramolecular aza -Michael reaction, and an intramolecular S N 2 cyclization to construct multisubstituted nitrogen-containing heterocycles. In addition, our total synthesis led to the stereochemical reassignment on the decahydroquinoline ring of senepodine F.",10.1021/acs.orglett.3c00133,2023-02-10,0.6473316424816457
Organic Letters,Total Synthesis of Asperaculin A,"The racemic total synthesis of asperaculin A, a sesquiterpenoid lactone with an unprecedented structure, has been accomplished in 17 steps from 3-methyl-2-cyclopentenone. Key features of the synthesis are the construction of a central all-carbon quaternary center using the Johnson-Claisen rearrangement, stereocontrolled introduction of a cyano group, and acid-mediated γ-lactonization.",10.1021/acs.orglett.3c01530,2023-06-13,0.6473265416816413
Journal of Organic Chemistry,"Total Synthesis of (+)-Boronolide, (+)-Deacetylboronolide, and (+)-Dideacetylboronolide","Total synthesis of (+)-boronolide, (+)-deacetylboronolide, and (+)-dideacetylboronolide has been achieved from a single intermediate 26, which was synthesized in 11 steps from a d-mannitol-derived intermediate 8 in an overall yield of 10%. The key steps in the synthesis are inversion of a chiral center by taking an advantage of the inherent mechanism involved in the ring closing to an epoxide via intramolecular S(N)2 reaction and lactonization of a diol using Fetizons reagent. The strategy is amenable to preparation of analogues of (+)-boronolide in sufficient amount for further screening of biological activity.",10.1021/jo0269058,2003-04-17,0.6473200951195225
Organic Letters,Modular Total Synthesis of the 5/5-Spirocyclic Spiroindimicins,"Total syntheses of the 5/5-spirocyclic indoline alkaloids (±)-spiroindimicins B, C, D, E, F, and G have been achieved via a modular approach. Our route features direct coupling of halogenated pyrrolemetal and isatin partners, Suzuki coupling to append the indole unit, Lewis acid-mediated spirocyclization, and divergent functionalization to give various family members. These syntheses are concise (six or seven steps from commercial materials) and highly amenable to analogue synthesis.",10.1021/acs.orglett.3c03131,2023-11-20,0.6473035022404129
Journal of the American Chemical Society,"Total Synthesis of an Antitumor Antibiotic, Fostriecin (CI-920)","The total synthesis of an antitumor antibiotic, fostriecin (CI-920), via a highly convergent route is described. A characteristic feature of the present total synthesis is that the synthesis was achieved via a coupling procedure of three segments A, B, and C. The unsaturated lactone moiety of fostriecin, corresponding to segment A, was constructed from a known Horner-Emmons reagent, and the stereochemistry of the C-5 position was introduced by asymmetric reduction with (R)-BINAl-H. Segment B having a series of stereogenic centers was synthesized from (R)-malic acid and the stereogenic centers at the C-8 and C-9 positions were prepared by a combination of Wittig reaction and Sharpless asymmetric dihydroxylation reaction. The conjugated Z,Z,E-triene moiety of fostriecin, corresponding to segment C, was eventually constructed by Wittig reaction and Stille coupling reaction. The phosphate moiety, which is known to be essentially important for the antitumor activity, was introduced via two routes: (i) direct phosphorylation of the monohydroxyl derivative in which other hydroxyl groups are protected with silyl groups; (ii) cyclic phosphorylation and selective cleavage of the cyclic phosphate derivative. Although the former route is basically the same as those reported by other groups, the latter route is novel and more effective than the former one. The present total synthesis would serve as a versatile synthetic route to not only fostriecin, but also its various analogues including stereoisomers.",10.1021/ja030133v,2003-06-17,0.6472993420737567
Journal of Organic Chemistry,"1,3-Diaxially Substituted <i>trans</i>-Decalins: Potential Nonsteroidal Human Progesterone Receptor Inhibitors","On the basis of molecular modeling and QSAR analysis of the known human progesterone receptor (hPR) inhibitor Mifepristone (RU-486) and other hPR ligands, a new class of potential nonsteroidal hPR inhibitors was designed. The parent racemic compound 1 was synthesized through an efficient 13-step synthetic pathway. The key constructive steps are a stereoselective epoxide ring opening and the reductive Heck cyclization to form the main framework of (+/-)-1. The current established flexible synthetic route allows for further chemical diversification.",10.1021/jo800947m,2008-09-05,0.647296043380808
Synthesis,First Total Synthesis of a Cytotoxic Derivative of the Natural Product Aaptamine,"A synthetic sequence to the benzonaphthyridinone framework is described. The key step is a one-pot, base-catalyzed vicarious nucleophilic substitution followed by ring closure. Additionally, the synthesis represents the application of a vicarious nucleophilic substitution in the total synthesis of a cytotoxic aaptamine derivative.",10.1055/s-0036-1588752,2017-03-17,0.6472835834475412
Journal of the American Chemical Society,Total Synthesis of Gymnocin-A,"A highly convergent total synthesis of gymnocin-A, a cyctotoxic polyether marine natural product, has been achieved. The synthesis features Suzuki-Miyaura coupling of the ABCD and FGHIJKLMN rings, stereoselective introduction of the C17 hydroxyl group, ring-closure of the F ring, and a late-stage incorporation of a 2-methyl-2-butenal side chain.",10.1021/ja038547b,2003-11-01,0.6472680461186824
Tetrahedron,"An efficient one-pot synthesis of novel polysubstituted 4-amino-2,3-dihydropyridines",,10.1016/j.tetlet.2011.01.017,2011-01-24,0.6472534171922641
Tetrahedron,One-step synthesis of oxazolinoazetidinones from penicillin sulfoxides: potential intermediates for 1-oxacephem synthesis,,10.1016/s0040-4039(01)81835-9,1981-01-01,0.6472436683089284
Journal of the American Chemical Society,Total Synthesis of the Potent cAMP Signaling Agonist (−)-Alotaketal A,We have developed a convergent synthetic route to the potent cAMP signaling agonist (-)-alotaketal A that employs two stages of SmI(2)-mediated reductive allylation reactions for assembling the polycycle and fragment coupling. Also notable are a Hg(OAc)(2)-mediated selective alkene oxidation and the subtlety of the formation of the unprecedented spiroketal ring system. The probes AKAR4 and ICUE3 were used to evaluate the cAMP singaling agonistic activity of (-)-alotaketal A and elucidate its structure-activity relationship.,10.1021/ja303529z,2012-05-07,0.6472272158375663
Journal of Organic Chemistry,Stereoselective Total Synthesis of (+)-Streptazolin by Using a Temporary Silicon-Tethered RCM Strategy,A stereoselective total synthesis of (+)-streptazolin 1 was accomplished starting from readily available aminocyclopentenol (-)-7. The synthetic sequence highlights an intramolecular aldol condensation strategy to construct the piperidine core and a silicon-tethered ring-closing metathesis strategy to install the Z exocyclic ethylidene side chain of streptazolin. Separate protodesilylation and Tamao oxidation of a common intermediate 32 afforded streptazolin and the precursor for 13-hydroxystreptazolin. The overall yield for (+)-streptazolin 1 from aminocyclopentenol (-)-7 was 4.8% for a total of 16 steps.,10.1021/jo060555y,2006-06-13,0.6472188227665502
Organic Letters,Concise Total Synthesis of Spirocurcasone,"A concise total synthesis of spirocurcasone was accomplished. Key features of the synthesis involved a vinylogous Mukaiyama aldol reaction, a Carroll rearrangement of β-keto allyl ester derivative, an intramolecular aldol condensation, and a spiro ring formation by ring-closing metathesis of the pentaene compound. This synthetic work was complete in nine steps from (S)- or (R)-perillaldehyde without the use of protecting groups. Interestingly, the optical rotation of the synthetic spirocurcasone was different from the reported value of the natural product.",10.1021/ol400228v,2013-02-28,0.6472072445963273
Journal of the American Chemical Society,Total Synthesis of the Antitumor Marine Sponge Alkaloid Agelastatin A,"The first total synthesis of the cytotoxic marine metabolite agelastatin A ( 1 ) has been achieved in about 14 steps performed in 12 operations in approximately 7% overall yield starting from cyclopentadiene. Hetero Diels−Alder cycloaddition of cyclopentadiene with N -sulfinyl methyl carbamate ( 7 ) afforded cycloadduct 8, which without purification was converted to allylic sulfoxide 9 and then by a [2,3]-sigmatropic rearrangement into bicyclic oxazolidinone 11 . The C-5a nitrogen was introduced into the oxazolidinone Boc derivative 16 by a Sharpless/Kresze allylic amination with SES sulfodiimide 12c . Palladium-promoted cyclization of 2-acyl pyrroles 20 and 21 via a π-allylpalladium intermediate 22 led to ABC-tricycles 23 and 24, respectively. A hydroxyl urea D-ring model system was constructed by hydroborating 24, leading eventually to keto amide 31 and then to tetracycle 33 . A modified strategy was developed for synthesis of the pivotal tricyclic ketone 58, involving as key steps a chemoselective hydrolysis of N -Boc oxazolidinone 54 and an internal conjugate addition of pyrrolo cyclopentenone 57 . A TMS group was used as a convenient substitute for the C-1 bromine substituent of agelastatin A, and thus silylpyrrole 58 could be converted to bromopyrrole 59 . Finally, the D-ring could be annulated onto an α-amino ketone derived from 59 using methyl isocycanate, providing racemic agelastatin A ( 1 ).",10.1021/ja992487l,1999-09-29,0.6472020367420506
European Journal of Organic Chemistry,Chemoenzymatic Synthesis of Hygromycin Aminocyclitol Moiety and its C2 Epimer,"This manuscript describes the enantioselective synthesis of the aminocyclitol moiety of the antibiotic hygromycin A in eight steps and 39 % overall yield from a non‐chiral starting material. The sequence made use of an initial enzymatic step to transfer chirality to an aromatic ring and was followed by selective organic chemistry transformations (oxidation, protection, azidation, hydrolysis) of the six‐membered ring in order to achieve the target. The approach is also amenable to the synthesis of other related unnatural analogues as exemplified by the synthesis of the C2 epimer of the natural aminocyclitol. All the intermediates were fully characterized, and the absolute stereochemistry assigned by spectrometric methods.",10.1002/ejoc.201801424,2018-11-29,0.6471831922952717
Organic Process Research & Development,"An Alternative Approach to Achieve Enantiopure (3<i>S</i>)-4-Benzyl-3- (4-fluorophenyl)morpholin-2-one:  A Key Intermediate of Aprepitant, an NK1 Receptor Antagonist","An efficient and alternative synthesis of enantiomerically pure (3 S )-4-benzyl-3-(4-fluorophenyl)morpholin-2-one ( S )-(+)- 2 ), a key intermediate in the synthesis aprepitant ( 1 ), is described. The key resolution of N -benzylglycinamide, (±)- 9, is achieved via diastereomeric salt crystallization using (+)-di- p -toluoyltartaric acid (DPTTA) as the resolving agent to furnish ( S )-(+)- 9 . Alkylation of ( S )-(+)- 9 with 2-bromoethanol followed by stereocontrolled cyclization of obtained ( S )-(+)- 10 afforded the desired enantiomer ( S )-(+)- 2 with good yields and enantiopurity (>98%). The reaction conditions were optimized to make the process robust in order to implement at the commercial scale.",10.1021/op700030d,2007-05-01,0.6471793119817699
Journal of Organic Chemistry,Synthesis of a C<sub>29</sub>−C<sub>51</sub> Subunit of Spongistatin 1 (Altohyrtin A) Starting from (<i>R</i>)-3-Benzyloxy-2-methylpropan-1-ol,"A protected C(29)-C(51) subunit ((+)-38) of spongistatin 1 has been obtained. Key steps involve the aldol condensation of (3S, 4R)-3-methyl-7-[(p-methoxybenzyl)oxy]-4-[(triethylsilyl)oxy]octan- 2-o ne ((-)-6) with (tert-butyl)dimethylsilyl 4-deoxy-2, 3-di-O-(methoxymethyl)-4-methyl-6-O-(tert-butyl)dimethylsilyl)-bet a-D -glycero-L-gluco-heptodialdo-1,5-pyranoside ((+)-7) and a C-glycosidation of (4R,7R&S,E)-7, 8-dichloro-2-methylidene-1-(trimethylsilyl)oct-5-en-4-yl p-methoxybenzoate (16). Aldehyde (+)-7 was derived from (R)-3-benzyloxy-2-methylpropan-1-ol ((+)-10) in 13 formal steps but requiring the isolation of five intermediate products only. The longest linear synthetic scheme converts (+)-10 into (+)-38 in 2% overall yield (isolation of 11 intermediate products).",10.1021/jo991642b,2000-05-06,0.6471776393704357
Organic Letters,"Asymmetric Synthesis of (+)-L-733, 060 and (+)-CP-99, 994 Based on a New Chiral 3-Piperidinol Synthon","[reaction: see text] Selective and potent neurokinin substance P receptor antagonists (+)-L-733, 060 (1) and (+)-CP-99, 994 (2) have been synthesized starting from a new (3S)-piperidinol synthon derived from l-glutamic acid. The methods featured a C-2 regioselective reduction of glutarimide (9), Lewis acid-promoted Si to C-2 phenyl group migration of 10, and stereoselective reduction of acetylated oxime 19 as the key steps.",10.1021/ol034505g,2003-05-01,0.6471653306779137
Angewandte Chemie International Edition,Total Synthesis of (−)‐Albocycline,"The macrolactone natural product (-)-albocycline is a promising antibiotic candidate for the treatment of both methicillin resistant Staphylococcus aureus (MRSA) and vancomycin-resistant strains. Herein we report a concise total synthesis of (-)-albocycline in 14 steps from commercially available methyl (R)-3-hydroxybutyrate. Novel key steps include the highly regio- and stereoselective reactions of chiral N-sulfinyl metallodienamines (NSMDs) with aldehydes and the Davis oxaziridine, in addition to the Horner-Wadsworth-Emmons olefination of N-sulfinyl imines.",10.1002/anie.201702530,2017-04-21,0.6471633111962286
Journal of Organic Chemistry,"Enantio- and Stereospecific Syntheses of 15(<i>R</i>)-Me-PGD<sub>2</sub>, A Potent and Selective DP<sub>2</sub>−Receptor Agonist","The first total synthesis of 15(R)-Me-PGD2 3 is reported. The synthesis is based on the enantioselective and stereospecific syntheses of synthon 17 and its attachment to the five-membered ring by a olefin cross metathesis reaction. This approach permits the introduction of a side chain with a predetermined stereogenic center into the prostanoid ring, resulting in the synthesis of 15R-methyl prostaglandin D2 and allows rapid access to other prostanoids.",10.1021/jo801190m,2008-08-14,0.6471631956623638
Organic Process Research & Development,"Evaluation of Kilogram-Scale Sonagashira, Suzuki, and Heck Coupling Routes to Oncology Candidate CP-724,714","The synthesis of the anti-cancer compound 2-methoxy- N -(3-{4-[3-methyl-4-(6-methyl-pyridin-3-yloxy)phenylamino]quinazolin-6-yl}- E -allyl)acetamide (CP-724,714) ( 1 ) on multikilogram scale using several different synthetic routes is described. Application of the Sonogashira, Suzuki, and Heck couplings to this synthesis was investigated to identify a safe, environmentally friendly, and robust process for the production of this drug candidate. A convergent and selective synthesis of the candidate was identified which utilizes a Heck coupling of a protected allylamine to install the critical olefin.",10.1021/op050039u,2005-06-01,0.6471588983450495
Journal of the American Chemical Society,Alkynyliodonium Salts in Organic Synthesis. Application to the Total Synthesis of (−)-Agelastatin A and (−)-Agelastatin B,"The asymmetric total syntheses of (-)-agelastatin A and (-)-agelastatin B were accomplished in 14 steps each from (R)-epichlorohydrin. The pivotal transformation in both sequences was a sulfinate-promoted cyclization of an alkynyliodonium salt to furnish a key functionalized cyclopentene intermediate. Selective bromination in the final step led to either agelastatin A or agelastatin B, depending upon conditions.",10.1021/ja027121e,2002-07-12,0.6471483159600974
Organic Process Research & Development,"Efficient, Scalable Synthesis of Functionalized Pyrrolo[2,1-<i>f</i>][1,2,4]triazines","An efficient, scalable synthesis of functionalized 5-fluoropyrrolo[2,1- f ][1,2,4]triazines was developed from readily available starting materials. The synthesis is highlighted by a safe, Cu mediated difluoroacetate addition to vinyl TMS, selective formylation of a 3-fluoropyrrole, and sequential imine formation followed by cyclization to the triazine core. Addition of other electrophiles to 3-fluoropyrrole was also shown to be equally selective.",10.1021/acs.oprd.4c00116,2024-05-07,0.6471179777627504
Organic Letters,Total Synthesis of (±)-Scirpene,"The racemate of scirpene, 12,13-epoxytrichothec-9-ene, was synthesized from 3-methoxyacetophenone. The key step in the synthesis is the palladium-mediated ring expansion reaction of the vinylcyclobutanol derivative, prepared via the oxidative ring expansion reaction of the cyclopropylidene. (3 S *)-3-[(1 S *,6 S *)-3-Methyl-9-oxabicyclo[4.3.0]non-2-en-6-yl]-3-methyl-2-methylenecyclo-pentan-1-one formed from the reaction was converted into (±)-scirpene through the ring opening of tetrahydrofuran part, followed by cyclization for construction of the desired skeleton.",10.1021/ol9901164,1999-06-24,0.6471068966187558
Journal of the American Chemical Society,Furans as Versatile Synthons: Total Syntheses of Caribenol A and Caribenol B,"Two complex norditerpenoids, caribenols A and B, were accessed from a common building block. Our synthesis of caribenol A features the diastereoselective formation of the seven-membered ring through a Friedel-Crafts triflation and a late-stage oxidation of a furan ring. The first synthesis of caribenol B was achieved using an intramolecular organocatalytic α-arylation. An unusual intramolecular aldol addition was developed for the assembly of its cyclopentenone moiety, and the challenging trans-diol moiety was installed through a selective nucleophilic addition to a hydroxy 1,2-diketone. Our overall synthetic strategy, which also resulted in a second-generation synthesis of amphilectolide, confirms the usefulness of furans as powerful nucleophiles and versatile synthons.",10.1021/jacs.7b00234,2017-02-21,0.647105884202748
Journal of Organic Chemistry,Total Synthesis of Geldanamycin,"The total synthesis of geldanamycin, a well-known polyketide that exhibited potent anticancer activity by inhibiting Hsp90, was finished in 26 long linear steps with 2.65% overall yield. High convergency of the synthesis was achieved by the disconnection between C12 and C13 that gives C5-C12 and C13-C21 fragments as major building blocks. The use of an alkynyl ketone as the precursor of the C5-C12 fragment enabled a reagent-controlled establishment of C7 chirality and a highly flexible substituent exchange at C8, making the synthetic route suitable for deep-seated structural modifications on geldanamycin.",10.1021/acs.joc.1c01582,2021-10-16,0.647102349624834
Journal of Organic Chemistry,"Scalable Synthesis of Enantiomerically Pure <i>syn</i>-2,3-Dihydroxybutyrate by Sharpless Asymmetric Dihydroxylation of <i>p</i>-Phenylbenzyl Crotonate","An efficient four-step synthetic route to the useful chiral building block (2R,3S)-dihydroxybutyric acid acetonide in >95% ee is detailed. The sequence is readily scaled, requires no chromatography, and allows for efficient recycling of p-phenylbenzyl alcohol, an expedient for enantio- and diastereoenrichment by recrystallization.",10.1021/jo2016746,2011-09-07,0.6470835759990469
Organic Process Research & Development,Exploratory Process Development of Lorlatinib,"The original synthesis of lorlatinib ( 1 ) was applied and improved in the first GMP campaign. In this approach, a slow addition of the boronate ester was critical in suppressing the formation of a homocoupled impurity in the Suzuki–Miyaura coupling, and the chemoselective hydrolysis of methyl ester was accomplished by potassium trimethylsilanoate. The synthesis was completed with macrocyclic amidation followed by deprotection of the Boc groups. A thorough process safety evaluation of HATU enabled its use as the coupling reagent for the macrocylic amidation, which improved the yield and eliminated the only chromatographic operation in the synthetic sequence.",10.1021/acs.oprd.8b00210,2018-08-01,0.647082713936886
Journal of Organic Chemistry,Catalytic Asymmetric Synthesis of a Tertiary Benzylic Carbon Center via Phenol-Directed Alkene Hydrogenation,"An expeditious synthetic approach to chiral phenol 1, a key building block in the preparation of a series of drug candidates, is reported. The strategy includes a cost-effective and readily scalable route to cyclopentanone 3 from isobutyronitrile (10). The sterically hindered and enolizable ketone 3 was subsequently employed in a challenging Grignard addition mediated by LaCl(3)·2LiCl. A novel preparation of the lanthanide reagent required for this transformation is described. To complete the process, a highly enantioselective hydrogenation step afforded the target (1). The importance of the phenol group to the success of this asymmetric transformation is discussed.",10.1021/jo200941r,2011-06-01,0.6470810264761508
Organic Letters,Stereoselective Total Synthesis of Rhodocoranes I and J,"We report the stereoselective total synthesis of rhodocoranes I and J in 10 steps and 16.4% overall yield from ( S )-limonene. The synthesis was accomplished through the convergent assembly of a highly substituted chiral cyclopentanone and a lithiated furanyl silyl ketene acetal. The requisite cyclopentanone framework was strategically constructed from the chiral pool, ( S )-limonene, through a sequence of steps that included a hydroboration/oxidation, ozonolysis, aldol condensation, reduction, and palladium-catalyzed diastereoselective allylic transposition. This study provides a general approach to the synthesis of the rhodocorane family, known for their antibacterial, antifungal, and cytotoxic properties.",10.1021/acs.orglett.4c02764,2024-09-26,0.6470727451802848
Journal of the American Chemical Society,"Total Synthesis of Aconicarmisulfonine A, a Sulfonated Diterpene Alkaloid","High Resolution Image Download MS PowerPoint Slide Diterpene alkaloids have fascinated the synthetic community for well over half a century and have long documented use in the treatment of pain and other ailments. Recently Shi and Zhang isolated a new class of sulfonated diterpene alkaloids from the roots of Aconitum carmichaelii . These zwitterionic alkaloids possess several unprecedented new ring systems and displayed potent analgesic properties in preliminary pain model studies in mice. Herein we describe synthetic entry into this subclass of C 20 diterpene alkaloids via a total synthesis of the most potent analgesic member aconicarmisulfonine A, which features an unusual sulfonated bicyclo[3.3.1]nonane core. Key synthetic maneuvers include a Ir-catalyzed caprolactam synthesis, a stereoselective Mannich cyclization, and a highly diastereoselective Mukaiyama–Michael cascade. A late-stage thiol to sulfonate oxidation completed the synthesis.",10.1021/jacs.5c17047,2025-12-08,0.6470534050565745
Journal of Organic Chemistry,Studies on the Synthesis of Apoptolidin: Synthesis of a C<sub>1</sub>–C<sub>27</sub> Fragment of Apoptolidin D,"Synthesis of a C(1)-C(27) fragment, a key intermediate in the synthesis of apoptolidin D, is reported. The synthesis involves a combination of Heck coupling and Horner-Wadsworth-Emmons reaction for the C(1)-C(7) trienoate portion and an efficient Suzuki cross-coupling protocol for the C(10)-C(13) diene portion.",10.1021/jo200934w,2011-08-09,0.6470466725778429
Journal of Organic Chemistry,Enantiopure <i>N</i>-Acyldihydropyridones as Synthetic Intermediates:  Asymmetric Synthesis of (−)-Septicine and (−)-Tylophorine,"A concise asymmetric synthesis of (-)-septicine (1) and (-)-tylophorine (2) was accomplished with a high degree of stereocontrol in eight and nine steps, respectively. Addition of 4-(1-butenyl)magnesium bromide to 1-acylpyridinium salt 3, prepared in situ from 4-methoxy-3-(triisopropylsilyl)pyridine and the chloroformate of (-)-trans-2-(alpha-cumyl)cyclohexanol, gave a 91% yield of diastereomerically pure dihydropyridone 7. Oxidative cleavage of 7 and subsequent reduction provided alcohol 6 in 81% yield. Conversion of 6 to the chloride followed by treatment with sodium methoxide gave indolizidinone 9 in high yield. Bromination and conjugate reduction of 9 with L-Selectride, and trapping the intermediate enolate with N-(5-chloro-2-pyridyl)triflimide, provided bromovinyl triflate 11. Palladium-catalyzed cross-coupling of excess (3,4-dimethoxyphenyl)zinc bromide and 11 gave (-)-septicine (1). On the basis of this synthesis, (-)-1 was assigned the Rconfiguration. Reaction of 1 with vanadium(V) trifluoride oxide in TFA/CH(2)Cl(2) effected oxidative coupling to give a 68% yield of (-)-tylophorine (2).",10.1021/jo9711495,1997-10-01,0.6470462174471423
Organic Letters,Total Synthesis of Icumazole A Using a Modified Cadiot–Chodkiewicz Coupling,"The first total synthesis of myxobacteria metabolite icumazole A ( 1 ) is reported. Key steps in the route include an organocatalyzed asymmetric self-aldol reaction followed by an acetate aldol reaction to form the stereotriad present in the oxazole moiety, an intramolecular Diels–Alder reaction to form the isochromanone, and an acetylide addition and selective methylation. The final steps involved a high-yielding modified Cadiot–Chodkiewicz coupling and stereoselective reduction to secure the Z,Z -diene and afford 1 .",10.1021/acs.orglett.3c04268,2024-01-29,0.6470411728418161
Journal of Organic Chemistry,Synthesis of 2′-Methyl-6-methoxyguanosine from the Parent Ribonucleoside Guanosine,A short and efficient synthesis of the nucleoside fragment contained in the NS5B nucleoside inhibitor BMS-986094 was achieved in 23% overall yield on a gram scale. The synthesis uses the widely available starting material guanosine via a short sequence ending in a Mukaiyama hydration reaction to establish the key tertiary alcohol moiety and set the C-2' methyl stereogenic center. This work resulted in a robust and scalable approach to this complex nucleoside.,10.1021/acs.joc.8b02194,2018-09-25,0.6470403389640684
Angewandte Chemie International Edition,An RCM‐Based Total Synthesis of the Antibiotic Disciformycin B,"Abstract The total synthesis of the potent new antibiotic disciformycin B ( 2 ) is described, which shows significant activity against methicillin‐ and vancomycin‐resistant Staphylococcus aureus (MRSA/VRSA) strains. The synthetic route is based on macrocyclization of a tetraene substrate to the 12‐membered macrolactone core by ring‐closing olefin metathesis (RCM). Although macrocyclization was accompanied by concomitant cyclopentene formation by an alternative RCM pathway, conditions were established to give the macrocycle as the major product. Key steps in the construction of the RCM substrate include a highly efficient Evans syn ‐aldol reaction, the asymmetric Brown allylation of angelic aldehyde, and the stereoselective Zn(BH 4 ) 2 ‐mediated 1,2‐reduction of an enone. The synthesis was completed by late‐stage dehydrative glycosylation to introduce the d ‐arabinofuranosyl moiety and final chemoselective allylic alcohol oxidation.",10.1002/anie.202004589,2020-06-19,0.6470307386153867
Organic Process Research & Development,Process Development of the HCV NS5B Site D Inhibitor MK-8876,"We describe the route development and multikilogram-scale synthesis of an HCV NS5B site D inhibitor, MK-8876. The key topics covered are (1) process improvement of the two main fragments; (2) optimization of the initially troublesome penultimate step, a key bis(boronic acid) (BBA)-based borylation; (3) process development of the final Suzuki–Miyaura coupling; and (4) control of the drug substance form. These efforts culminated in a 28 kg delivery of the desired active pharmaceutical ingredient.",10.1021/acs.oprd.5b00405,2016-01-25,0.6470275426709375
Journal of Organic Chemistry,Sulfinamide-Based Approach for Synthesis of the Pentacyclic Core of Nakadomarin A,The synthesis of the pentacyclic core of alkaloid nakadomarin A is described. Key reactions in the synthesis include the elaboration of a Michael addition product obtained in the addition of a chiral sulfinyl imidate to an unsaturated ester prepared from 3-furyl aldehyde; diastereoselective allylation of a β-keto ester; and intramolecular cyclization of furan onto an iminium ion.,10.1021/acs.joc.5c02254,2025-12-16,0.646989725482834
Organic Letters,Concise Synthesis of Capuramycin,"A concise total synthesis of capuramycin (1), a promising preclinical TB drug lead, is achieved by high-yield formations of the cyanohydrin 5a and 4'',5''-glycal derivative 12. Capuramycin can be synthesized in eight steps from the uridine building block 5a with >30% overall yield. The synthetic intermediates reported here are useful for generation of analogs to improve pharmacokinetic properties of capuramycin.",10.1021/ol900458w,2009-04-30,0.6469849496626354
Tetrahedron,Total synthesis of a potent thromboxane A2 antagonist,,10.1016/s0040-4039(00)97481-1,1990-01-01,0.6469418927250168
Synthesis,An Improved Synthesis of Ethyl 2-(Dicyanomethylene)propanoate,,10.1055/s-1974-23401,1974-01-01,0.6469399368614551
Synthesis,Efficient Synthesis of 4-Amino-4-deoxy-l-arabinose and Spacer-Equipped 4-Amino-4-deoxy-l-arabinopyranosides by Transglycosylation Reactions,"Methyl 4-azido-4-deoxy-β-L-arabinopyranoside has been synthesized in five steps starting from methyl β-D-xylopyranoside in a multigram scale without chromatographic purification in 78% overall yield. The transformation relied on selective tosylation/nosylation at O-4 followed by acylation, S(N)2 displacement with sodium azide and subsequent deprotection. The methyl 4-azido-4-deoxy-arabinoside was then converted into allyl, propenyl, ω-bromohexyl and chlorethoxyethyl spacer glycosides by transglycosylation with the respective alcohols in good yields and fair anomeric selectivity. Reduction of the azido group and further transformations of the aglycon afforded ω-thiol-containing spacer derivatives. Coupling to maleimide-activated BSA provided a potent immunogen which was used to generate murine and rabbit polyclonal sera binding to LPS-core epitopes containing 4-amino-4-deoxy-arabinose residues.",10.1055/s-0030-1258174,2010-07-16,0.6469231952653596
Journal of Organic Chemistry,"First Enantioselective Total Synthesis of (8<i>S</i>,12<i>R</i>,15<i>S</i>)-Prostaglandin J<sub>2</sub>","Enantioselective synthesis of natural PGJ(2) has been accomplished for the first time starting from the commercially available enantiopure aldehyde 7 in 10% overall yield. The key reaction was a novel prostaglandin class interconversion, i.e., an allylic 1,3-transposition across alcohol 9 derived from compound 14 in 73% overall yield. In principle, the unnatural enantiomer of PGJ(2) could be obtained starting from the commercially available enantiopure monobenzoate 7a following our strategy.",10.1021/jo034502h,2003-07-03,0.6468757673019245
Tetrahedron,A facile phenol synthesis. An improved route to 6-methoxy-2-tetralone.,,10.1016/s0040-4039(00)72916-9,1966-01-01,0.6468565262017824
Tetrahedron,A new strategy for the synthesis of carbapenems. A formal total synthesis of (+)-thienamycin.,,10.1016/s0040-4039(00)74078-0,1993-07-01,0.646837751659779
Journal of Organic Chemistry,"Total Synthesis of Racemic Laurenditerpenol, an HIF-1 Inhibitor","The convergent total synthesis of the HIF-1 inhibitor laurenditerpenol 1 and its diastereomer 1' is reported. The key step involves the Julia-Kocienski olefination-reduction process between the sulfone 55 and the aldehyde 54. The unusual trimethylated oxanorbornane sulfone 55 was successfully synthesized from the known exo Diels-Alder adduct 24 of 2,5-dimethylfuran 7 and maleic anhydride 23 in 8 steps. The aldehyde 54 was prepared by ring-opening and elaboration of lactone 41. In addition, four analogues of 1 were also successfully synthesized for biological testing.",10.1021/jo902029x,2009-10-29,0.646827974260264
Organic Letters,"Enantioselective Synthesis of 2,6-<i>cis</i>-Disubstituted Tetrahydropyrans via a Tandem Catalytic Asymmetric Hydrogenation/Oxa-Michael Cyclization: An Efficient Approach to (−)-Centrolobine","A highly efficient one-pot process via a tandem reaction of catalytic asymmetric hydrogenation and oxa-Michael cyclization for the synthesis of 2,6-cis-disubstituted tetrahydropyrans has been developed (ee up to 99.9%, cis/trans-selectivity up to 99:1). This method provides a concise route to (-)-centrolobine (68.8% yield, three steps).",10.1021/ol3020144,2012-08-30,0.6468275677702338
Organic Letters,Total Synthesis of Luminacin D,"[reaction: see text] A highly convergent synthesis of the angiogenesis inhibitor luminacin D has been achieved in 13 linear steps (19 steps total, 5.3% overall yield) utilizing a samarium(II) iodide-mediated mixed tandem aldol/Evans-Tishchenko reaction to construct the carbohydrate precursor. The modular synthetic design will allow derivatization at key positions necessary for biochemical mode of action studies.",10.1021/ol026382q,2002-07-31,0.6468109064549532
Synlett,Highly Efficient Synthesis of (+)-Nimbiol and Other Podocarpanes Derivatives from Sclareol,"A new access to tricyclic diterpenes of podocarpane ­skeleton has been opened, in excellent overall yields, and an efficient synthesis of (+)-nimbiol from sclareol has been achieved.",10.1055/s-2007-982533,2007-06-01,0.6467981811008947
Organic Process Research & Development,Development of Large-Scale Syntheses of Ropinirole in the Pursuit of a Manufacturing Process<sup>1</sup>,"Two plant syntheses of ropinirole {4-[2-(di- n -propylamino)ethyl]-1,3-dihydro-2 H -indolin-2-one hydrochloride, SK&F-101468-A} using the ferric chloride mediated cyclisation of β-nitrostyrenes to form 3-chlorooxindoles as the key step are described. The first synthesis suffered the severe limitation of the final-step chemistry being nonselective in the reaction between di- n -propylamine and the bromide precursor to ropinirole as both substitution and elimination pathways were promoted and by-product formation at a level of 40% resulted. This problem was rectified in the latter synthesis by the more selective reaction between di- n -propylamine and the sulfonate ester precursor promoting ropinirole formation to a level of 88%. This second synthesis is now used as the commercial route, and problems (and their solutions) identified during the development of this route are now described. The identification of novel by-products which enabled the Sommelet oxidation step to be optimised is also reported. A unimolecular decomposition mechanism during hydrolysis of the hexaminium salt to form the key benzaldehyde intermediate is proposed and substantiated with experimental data.",10.1021/op970037c,1998-01-01,0.6467290018933083
Tetrahedron,New diastereoselective synthesis of a novel chiral λ-(Aminoalkyl)-α-hydroxy-λ-lactones and their application for the synthesis of renin inhibitors,,10.1016/s0040-4039(00)80382-2,1988-01-01,0.6467065829097206
Synlett,Short Synthesis of (+)-1-Deoxynojirimycin via a Diastereoselective Reductive Coupling of Alkyne and α-Chiral Aldehyde,"A short, highly diastereoselective synthesis of (+)-1-deoxynojirimycin from readily available l-isoserine with overall yield of 32.0% in eight steps is described. The key step includes a diastereoselective syn-coupling reaction of Cbz-protected (S)-iso­serinal acetonide 6 and vinylzinc nucleophile, generated conveniently from a protected propargyl alcohol 7 by a hydrozirconation-transmetalation sequence. Significantly, not only does this simple flexible strategy provide a concise approach to (+)-1-deoxynojirimycin, but it also can readily be adopted for the synthesis of other stereoisomers of the 1-deoxynojirimycin family from l- or d-iso­serine through different coupling conditions and stereoselective ­epoxidation of allylic alcohol 4 by the same procedures.",10.1055/s-0031-1289546,2011-10-19,0.6466942748994056
Angewandte Chemie International Edition,"Total Synthesis, NMR Solution Structure, and Binding Model of the Potent Histone Deacetylase Inhibitor FR235222","An alternative route: The fungal metabolite FR235222, a potent inhibitor of mammalian histone deacetylase (HDAC), has been synthesized. Key steps are the preparation of unusual amino acids Ahoda and (2R,4S)-MePro. A 3D model for cyclopeptide inhibitor interaction with the HDAC active site (see picture) highlights the differences between the binding mode of small-molecule and cyclopeptide inhibitors.",10.1002/anie.200501995,2005-11-28,0.6466890729036946
Organic Process Research & Development,Some Items of Interest to Process R&amp;D Chemists and Engineers,"■ SYNTHESIS OF 2-CYANO-4-CHLOROPYRIDINES Veerareddy and co-workers of Suven Life Sciences have reported (J.Heterocycl.Chem.2011, 48, 961) an improved procedure for the synthesis of 2-cyano 4-chloropyridines.Such products are useful building blocks en route to more elaborate pyridines, e.g.via SnAr of the 4-chloro group or manipulation of the 2-cyano group.Thus, direct conversion of 4-nitropyridine N-oxides into 2-cyano-4-chloropyridines was achieved via sequential addition of trimethylsilylcyanide and ethyl chloroformate in dichloromethane under mild conditions.Whilst most yields were modest (10-48%), this chemistry provides an advantage over other approaches that are restricted to 2-methyl 4-nitropyridine-N-oxides or that use highly toxic dimethylcarbamyl chloride. ■ GENERAL DIRECT SYNTHESIS OF BENZIMIDAZOLES FROM CARBOXYLIC ACIDSThe boric acid-catalysed condensation of a carboxylic acid and an amine is an efficient method for the synthesis of amides (see Organic Syntheses; 2005, Vol.81, p.262).Kocevar and Maras (Helv.Chim.Acta 2011, 94(10), 1860-1874) have extended this methodology to the preparation of benzimidazoles.Thus, treatment of 1,2-benzenediamine with a range of monocarboxylic acids in the presence of catalytic boric acid afforded the benzimidazole derivatives in typically good yield.Extension of the methodology to dicarboxylic acids such as malonic acid lead to both a decarboxylation benzimidazole product (65%) and cyclisation to the benzodiazepinedione (13%).Succinic acid reacted with 2 equiv of the diamine to yield a mixture of the mono-and bis-benzimidazoles.■ PRACTICAL SYNTHESIS OF RHO-KINASE INHIBITOR Shibuya of Kowa Research laboratories and collaborators from Fuji Chemical (Heterocycles 2011, 83(8), 1771-1781) report a scaleable approach to a novel chiral analogue of the known kinase inhibitor Fasudil.Initial attempts to prepare chlorosulfonyl isoquinoline 4 via direct sulfonyation (c.H 2 SO 4 /SO 3 ) proved problematic due to handling issues with 1 (m.pt 20-25 °C) and the need to neutralise large volumes of excess H 2 SO 4 .Acceptable yields in the sulfonation step were achieved by conversion of preformed sulfate salt 2 in neat sulfur trioxide without additional sulfuric acid.One-pot sequential addition of SO 3 and SOCl 2 to 2 yielded a mixture of sulfonyl chloride isomers.The desired isomer 4 was then isolated after crystallisation.Subsequent reaction with L-alaninol installed the chiral side chain.Mesylation of 5 afforded an intermediate N-sulfonylaziridine which underwent ring-opening with aminopropanol.Recrystallisation of the oxalate salt 6 removed the isomer resulting from 1′ aziridine ring-opening.Ring closure under Mitsunobu conditions completed the synthesis in overall 24% yield and >99.9 ee.",10.1021/op300014y,2012-02-10,0.6466514270497873
European Journal of Organic Chemistry,First Total Synthesis and Structural Confirmation of C13‐Butylrubber Oligomers,"The first total synthesis of an important C13 butyl rubber oligomer is reported. The structure of the oligomer, which is an important and potentially toxic extractable and leachable component of elastomeric closures, is confirmed by synthesis for the first time. The method described is scalable, making large quantities of the oligomer available for the first time for AMES toxicity studies. The challenging synthesis commences with isophorone and the key steps of the synthesis involve the development of highly novel dithoacetal chemistry, cuprate addition and Tebbe olefination.",10.1002/ejoc.201800496,2018-05-04,0.6466396756931134
Organic Letters,Two-Step Synthesis of the Immunogenic Bacterial Glycolipid BbGL1,Chemical synthesis of a bacterial glycolipid BbGL1 is reported in two steps starting from per-O-TMS D-galactose. The key features are glycosyl iodide mediated beta-stereoselective glycosylation in the absence of neighboring group participation and regioselective acylation.,10.1021/ol801780c,2008-09-18,0.6466183145648791
Journal of Organic Chemistry,Concise Total Synthesis of (−)-Spongotine A,The first asymmetric total synthesis of spongotine A is described. The oxidative synthesis of the imidazoline/ketone unit from keto aldehyde and diamine is a key step in this synthesis. The absolute stereochemistry of the asymmetric center of natural spongotine A is revealed as the (S)-configuration.,10.1021/jo701668s,2007-10-12,0.6465905713729152
Organic Letters,Asymmetric Synthesis of the Tropane Alkaloid (+)-Pseudococaine via Ring-Closing Iodoamination,"Ring-closing iodoamination of tert-butyl 2-hydroxy-7-[N-methyl-N-(α-methyl-p-methoxybenzyl)amino]cyclohept-3-ene-1-carboxylates proceeds with concomitant loss of the N-α-methyl-p-methoxybenzyl group to give the corresponding 8-azabicyclo[3.2.1]octane scaffolds in >99:1 dr. Subsequent elaboration of one of these templates provided access to (+)-pseudococaine hydrochloride, in seven steps and 31% overall yield from commercially available starting materials.",10.1021/ol3020607,2012-08-06,0.6465868236247615
Journal of Organic Chemistry,Total Synthesis of Nagelamide W,"), a pyrrole imidazole alkaloid of the nagelamide family isolated in 2013. The key approach in this work involves the construction of the 2-aminoimidazoline core of nagelamide W from alkene 6 through a cyanamide bromide intermediate. The synthesis of nagelamide W was accomplished with an overall yield of 6.0%.",10.1021/acs.joc.3c00867,2023-06-14,0.6465725600760288
Synthesis,"An Efficient Syntesis of 1,8-Naphthyridin-2(1<i>H</i>)-ones: Synthesis of Leukotriene Inhibitor SCH 37224","All articles of this category A new, efficient synthesis of 1,8-naphthyridin-2(1 H )-ones as applied to the synthesis of the leukotriene release inhibitor, 1,2-dihydro-1-phenyl-3-pyrrolidinio-2-oxo-1, 8-naphthyridin-4-olate inner salt (4) from methyl 2-phenylamino-3-pyridinecarboxylate, (1a) , has been described. Towards this synthesis a new reaction procedure for the N -chloroacylation of 1a was developed. The high yield for the rest of the synthesis was obtained by establishing reaction conditions that utilized the solubility, and the stability properties 4 .",10.1055/s-1991-26519,1991-01-01,0.6465639973226842
Organic Process Research & Development,"Stereoselective Bulk Synthesis of CCR2 Antagonist BMS-741672: Assembly of an All-<i>cis</i> (<i>S,R,R</i>)-1,2,4-Triaminocyclohexane (TACH) Core via Sequential Heterogeneous Asymmetric Hydrogenations","A concise bulk synthesis of stereochemically complex CCR2 antagonist BMS-741672 is reported. A distinct structural feature is the chiral all- cis 1,2,4-triaminocyclohexane (TACH) core, which was assembled through consecutive stereocontrolled heterogeneous hydrogenations: efficient Pt-catalyzed reduction of a β-enaminoester, directed by ( S )-α-methylbenzylamine as a low-cost chiral template, and reductive amination of a 3,4- cis -disubstituted cyclohexanone over sulfided Pt/C introduced a tert- amine, setting the third stereocenter in the all- cis cyclohexane core. The heterogeneous catalysts were recycled. Ester hydrolysis produced a γ-amino acid, isolated as its Na salt. A challenging Curtius reaction to introduce the remaining C–N bond at C-2 was strongly influenced by the presence of the basic tert- amine, providing a stereoelectronically highly activated isocyanate. Detailed mechanistic and process knowledge was required to enable clean trapping with an alcohol ( t -BuOH) while avoiding formation of side products, particularly an unusual carbamoyl phosphate. Deprotection, N -acetylation, and uncatalyzed S N Ar coupling with known 4-chloroquinazoline provided the final product. The resulting 12-step synthesis was used to prepare 50 kg of the target compound in an average yield of 82% per step.",10.1021/acs.oprd.6b00282,2016-10-13,0.6465439453315036
Synlett,Efficient Synthetic Route to Ravidosamine Derivatives,"All articles of this category Abstracts Concise synthesis of ravidosamine, the amino sugar constituent of ravidomycin and other antibiotics, has been achieved. The key steps include (1) regioselective reduction of benzylidene acetal with DIBAL, and (2) stereoselective reduction of oxime to the corresponding amine by using samarium diiodide in the ­presence of methanol.",10.1055/s-2005-864792,2005-01-01,0.6465032655870061
Journal of Organic Chemistry,Total Synthesis of Meayamycin B,"Meayamycin B is currently the most potent modulator of the splicing factor 3b subunit 1 and used by dozens of research groups. However, current supply for this natural product analogue is limited because of the lengthy synthetic scheme. Here, we report a more concise, more cost-effective, and greener synthesis of this compound by developing and employing a novel asymmetric reduction of a prochiral enone to afford an allylic alcohol with high enantioselectivity. In addition to this reaction, this synthesis highlights a scalable Mukaiyama aldol reaction, Nicolaou-type epoxide opening reaction, stereoselective Corey–Chaykovsky-type reaction, and a modified Horner–Wadsworth–Emmons Z -selective olefination. We also discuss a Z – E isomerization during the α,β-unsaturated amide formation. The new synthesis of meayamycin B consists of 11 steps in the longest linear sequence and 24 total steps.",10.1021/acs.joc.9b03370,2020-03-12,0.646495539973127
Organic Process Research & Development,Syntheses of a Selective Peroxisome Proliferator Activated Receptor Modulator and Practical New Preparations of 2-(4-Alkoxyphenyl)ethylamines,"This article describes chemistry that was developed to give access to multigram quantities of the selective peroxisome proliferator activated receptor modulator (SPPARM), compound 1 . 1 Fischer esterifications, phase transfer-catalyzed alkylations, amide couplings, crystallizations, and a new synthesis were developed to accomplish this task. In addition, an efficient method for preparing 2-(4-alkoxyphenyl)ethylamines 7a−d from tyramine 9 was developed that involves O-alkylation of intermediate Schiff base 11 and subsequent acid-catalyzed hydrolysis to afford the target molecules as crystalline hydrochloride salts.",10.1021/op800215a,2008-11-07,0.6464837416400263
Angewandte Chemie International Edition,Total Synthesis of Dictyodendrin A and B,In-do-line of fire: A highly efficient total synthesis of the title compounds features a novel benzyne-mediated one-pot indoline formation/cross-coupling sequence for the construction of a highly substituted key indoline intermediate. The peripheral substituents were then introduced onto the intermediate in a modular fashion to complete the total syntheses of dictyodendrin A and B.,10.1002/anie.201001966,2010-07-19,0.6464503659143861
Journal of Organic Chemistry,"Total Synthesis of Neuroprotective Agents, (+)-Lycibarbarine A and (−)-Lycibarbarine B","We describe the convergent total syntheses of lycibarbarines A and B which are potent neuroprotective agents recently isolated from the fruits of Lycium barbarum . The synthesis highlights the construction of a unique spiro oxazine heterocyclic motif imbedded in these natural products. The synthesis is accomplished from the commercially available 8-hydroxyquinaline and 2-deoxy- d -ribose as key starting materials. The synthesis features a Reimer–Tiemann reaction, selective amine alkylation with a keto tosylate derivative, and spiroketalization to form an oxazine core.",10.1021/acs.joc.3c00749,2023-06-02,0.6464237734054377
Journal of Organic Chemistry,"Synthesis of (±)-4,5-<i>dia</i>-Parthenolide, an Unnatural Parthenolide Stereoisomer","A short total synthesis of the novel unnatural parthenolide diastereomer (±)-4,5-dia-parthenolide was accomplished in 13 steps and an overall yield of 1.75% starting from commercially available (E,E)-farnesol. The challenging isopropenyl side chain oxidation was regioselectively achieved via a newly developed stepwise dihydroxylation procedure, employing a Bartlett-Smith iodocarbonate cyclization followed by iodide substitution and catalytic transesterification.",10.1021/acs.joc.6b01985,2016-10-11,0.6464128992437572
Synlett,"Process Development of Halaven®: Synthesis of the C1-C13 Fragment from d-(-)-Gulono-1,4-lactone","A 12-step kilogram-scale synthesis of the C1–C13 fragment, common to halichondrin B and the totally synthetic analogue Halaven ® (E7389, INN eribulin mesylate), is described. The synthesis features four crystalline intermediates which facilitates throughput, and enhances quality control of all stereogenic centers in the title compound.",10.1055/s-0032-1317919,2013-01-10,0.6464058502239773
Organic Letters,Total Synthesis of (−)-Xestosaprol N and O,"The first total synthesis of (-)-xestosaprol N and O is described. This synthetic work features a convergent strategy: (1) a Pd-catalyzed arylation followed by cyclization to build a naphthalene fragment (ring C, D); (2) utilization of (-)-quinic acid to construct the chiral hydroxyl group at C-2; (3) a substrate controlled intramolecular Heck reaction to construct a quaternary carbon center (ring B); (4) introduction of a hypotaurine moiety at a late stage to furnish the E ring.",10.1021/acs.orglett.7b03865,2018-01-19,0.6464001975915478
European Journal of Organic Chemistry,Total Synthesis of Lavendamycin by a [2+2+2] Cycloaddition,"Abstract The total synthesis of the bacterial‐derived, pentacyclic, antitumor antibiotic lavendamycin has been achieved through a highly convergent strategy. The key step of this synthesis is a ruthenium‐catalyzed [2+2+2] cycloaddition of an electron‐deficient nitrile to an alkynyl‐ynamide to prepare the carboline scaffold. The elaborate cycloaddition substrate is obtained in few steps by an N ‐ethynylation using alkynyliodonium salt chemistry and two palladium‐catalyzed cross‐coupling reactions. An efficient synthesis of a halogenated quinoline‐5,8‐dione building block starting from hydroquinone is presented.",10.1002/ejoc.201100131,2011-04-05,0.6463759101854545
Organic Process Research & Development,"Ruthenium-Catalyzed Direct Asymmetric Reductive Amination for the Synthesis of a Chiral Primary Amine Intermediate En Route to a PDE2A Inhibitor, TAK-915","High Resolution Image Download MS PowerPoint Slide Here, we report a novel, efficient ruthenium-catalyzed direct asymmetric reductive amination of an α-alkoxy ketone, a structural motif for which it is more challenging to implement such a transformation than 1,3-dicarbonyl compounds. The discovery of a novel ruthenium catalyst that was highly stable to air and moisture, as well as being readily prepared from commercially available reagents, enabled rapid access to a key synthetic chiral primary amine en route to TAK-915, an active pharmaceutical ingredient for a PDE2A inhibitor.",10.1021/acs.oprd.3c00088,2023-04-27,0.6463616039174147
Organic Letters,Rapid Synthesis of the<i>N</i>-Methylwelwitindolinone Skeleton,"An efficient, convergent synthesis of the core bicyclo[4.3.1]decane ring system of welwitindolinones is described. Key steps in the synthesis include an intramolecular palladium-catalyzed enolate arylation reaction to create the desired bicyclic skeleton and a Curtius rearrangement to install the bridgehead isocyanate unit. [reaction: see text]",10.1021/ol051043t,2005-07-12,0.6463605616105484
Synthesis,"A Convenient Two-Step Synthesis of Amino Acid Derived Chiral 3-Substituted [1,4]Benzodiazepin-2-ones","A new two-step route to chiral 3-substituted [1,4]benzodiazepin-2-ones is described, which involves the coupling of 2-nitrobenzyl bromide with a series of amino acids, followed by diazepine ring formation with Fe/AcOH at 110 °C.",10.1055/s-2005-869950,2005-01-01,0.6463591467049271
Journal of the American Chemical Society,Total Synthesis of (−)-Archazolid B,"A highly convergent synthesis of archazolid B, a potent and highly selective V-ATPase inhibitor, is described. A relay ring-closing metathesis reaction was used to form the 24-membered macrocyclic lactone, whereas the sensitive cis-triene moiety of the archazolids was assembled with a modified Stille coupling.",10.1021/ja0733033,2007-06-27,0.6463299575208316
Journal of Organic Chemistry,Application of Cross-Conjugated Heteroaromatic Betaines to the Synthesis of the Schizozygane Alkaloid (±)-Strempeliopine,"An efficient stereocontrolled route to the isoschizozygane alkaloid core has been developed utilizing an intramolecular 1,4-dipolar cycloaddition of a cross-conjugated heteroaromatic betaine. The resulting cycloadduct undergoes loss of COS, and further reduction delivers a 5a-azaacenaphthylene intermediate that was transformed into the isoschizozygane skeleton upon treatment with acid. A variation of this tactic was then employed for a synthesis of the hexacyclic framework of the shizozygane alkaloid (+/-)-strempeliopine. The key step of the synthesis corresponds to an intramolecular 1,4-dipolar cycloaddition of a heteroaromatic betaine across a tethered 4-((2-nitrophenyl)but-3-enyl) side chain. Catalytic reduction of the nitro group followed by reaction with NBS resulted in the formation of the required pentacyclic indoline framework of the target alkaloid. Closure of the final ring of the shizozygane skeleton was carried using an oxidative cyclization.",10.1021/jo901336z,2009-08-27,0.6463157102208896
Angewandte Chemie International Edition,A Divergent Enantioselective Strategy for the Synthesis of Griseusins,"The first enantioselective total synthesis of griseusin A, griseusin C, 4'-deacetyl-griseusin A, and two non-native counterparts in 11-14 steps is reported. This strategy highlights a key hydroxy-directed CH olefination of 1-methylene isochroman with an α,β-unsaturated ketone followed by subsequent stereoselective epoxidation and regioselective cyclization to afford the signature tetrahydro-spiropyran ring. Colorectal cancer cell cytotoxicities of the final products highlight the impact of the griseusin tetrahydro-spiropyran ring on bioactivity. As the first divergent enantioselective synthesis, the strategy put forth sets the stage for further griseusin mechanism-of-action and SAR studies.",10.1002/anie.201505022,2015-07-31,0.646304724932156
Journal of Organic Chemistry,"Total Synthesis of 10-Deoxymethynolide, the Aglycon of the Macrolide Antibiotic 10-Deoxymethymycin","A short and efficient total synthesis of 10-deoxymethynolide ( 2c ), the aglycon of 10-deoxymethymycin ( 1c ), has been accomplished in 16 steps and 12% overall yield from (S)-3- O - p -toluenesulfonyl-3-hydroxy-2-methylpropanal ( 15c ). The synthesis features an expeditious preparation of (+)- 5a, a synthetic equivalent of the Prelog−Djerassi lactonic acid, and the construction of a 12-membered lactone through an intramolecular Nozaki−Hiyama−Kishi coupling reaction.",10.1021/jo9809433,1998-10-01,0.6462838959010863
European Journal of Organic Chemistry,"Vitamin D: Enantioselective Synthesis of (3aR,4R,7aS)-4-Hydroxy-7a-methylperhydro-1-indenone, a Suitable CD-Ring Fragment","A practical synthesis of trans-hydrindanone 5a from (+)-Wieland−Miescher ketone 8 is described. The target molecule 5a is a suitable precursor for the synthesis of analogues of 1α,25-dihydroxyvitamin D3 modified at C-16, C-17 or C-20. During the total synthesis it was found that hydroboration of (1,1)-ethylenedioxy-8a-methyl-1,2,3,4,6,7,8,8a-octahydronaphthalene (11) leads to a cis-decalin 13 instead of the literature reported trans-fusion.",10.1002/1099-0690(200010)2000:20<3427::aid-ejoc3427>3.3.co;2-o,2000-10-01,0.6462661101297666
European Journal of Organic Chemistry,"Vitamin D: Enantioselective Synthesis of (3aR,4R,7aS)-4-Hydroxy-7a-methylperhydro-1-indenone, a Suitable CD-Ring Fragment","A practical synthesis of trans-hydrindanone 5a from (+)-Wieland−Miescher ketone 8 is described. The target molecule 5a is a suitable precursor for the synthesis of analogues of 1α,25-dihydroxyvitamin D3 modified at C-16, C-17 or C-20. During the total synthesis it was found that hydroboration of (1,1)-ethylenedioxy-8a-methyl-1,2,3,4,6,7,8,8a-octahydronaphthalene (11) leads to a cis-decalin 13 instead of the literature reported trans-fusion.",10.1002/1099-0690(200010)2000:20<3427::aid-ejoc3427>3.0.co;2-x,2000-10-01,0.6462661101297666
Tetrahedron,"A novel asymmetric synthesis of 2,5-dialkylpyrrolidines",,10.1016/s0040-4039(99)00058-1,1999-02-01,0.6462402009350346
Tetrahedron,"Asymmetric synthesis of myrioxazines A and B, novel alkaloids of Myrioneuron nutans",,10.1016/s0040-4039(02)01771-9,2002-10-01,0.6462402009350346
Journal of the American Chemical Society,Total Synthesis of (±)-Streptonigrin: De Novo Construction of a Pentasubstituted Pyridine using Ring-Closing Metathesis,"The synthesis of the potent antitumor agent (±)-streptonigrin has been achieved in 14 linear steps and 11% overall yield from ethyl glyoxalate. The synthesis features a challenging ring-closing metathesis reaction, followed by elimination and aromatization, to furnish a key pentasubstituted pyridine fragment.",10.1021/ja207835w,2011-09-23,0.6462355482986598
Journal of the American Chemical Society,Total Synthesis of (−)-Acutumine,"The first total synthesis of the tetracyclic alkaloid (-)-acutumine is described. Key reactions include an asymmetric ketone allylation mediated by Nakamura's chiral allylzinc reagent, an anionic oxy-Cope rearrangement, and the Lewis acid-promoted cyclization of an amine onto an alpha,beta-unsaturated dimethyl ketal.",10.1021/ja9024403,2009-04-28,0.6462334860825588
Organic Letters,Synthesis of the Pentacyclic Core of Citreamicin η,"The citreamicins comprise a novel class of polycyclic xanthone natural products that have not yet yielded to total synthesis. A concise 11-step synthesis of the pentacyclic core of citreamicin η is now reported that features the use of a general approach for the synthesis of 1,4-dioxygenated xanthones. The synthesis also showcases improved techniques for effecting regioselective bromination of certain substituted phenols and coupling of acetylides with hindered ketones.",10.1021/acs.orglett.6b03760,2017-02-08,0.646229207772317
Journal of the American Chemical Society,Total Synthesis of (±)-Phomactin B2 via an Intramolecular Cyclohexadienone Annulation of a Chromium Carbene Complex,"A total synthesis of (±)-phomactin B2 is described which has as its key step the intramolecular cyclohexadienone annulation of a Fischer carbene complex. The requisite carbene complex was prepared from geraniol in 11 steps and 12% overall yield. The key cyclohexadienone annulation produced both rings of the [9.3.1] pentadecane ring system of phomactin B2 in a single step in 60% yield and as a 4:1 mixture of diastereomers. The major diastereomer was taken on to the natural product in a series of steps that begins with a Peterson olefination. Initially, the Peterson olefination failed, but X-ray analysis of two intermediates in the diastereomeric series revealed that approach to the hindered carbonyl was blocked by a TIPS protecting group. Replacement of the TIPS group with a MOM group led to a facile Peterson olefination. Other notable steps in the synthesis include a stereoselective methylation of a cyclohexenone and hydroxyl-directed epoxidation of an alkene.",10.1021/ja074275r,2007-10-12,0.6462069568010839
Angewandte Chemie International Edition,"Total Synthesis of Δ<sup>12</sup>‐Prostaglandin J<sub>3</sub>, a Highly Potent and Selective Antileukemic Agent","A catalytic asymmetric total synthesis of the potent and selective antileukemic Δ(12)-prostaglandin J3 (Δ(12)-PGJ3) is described. The convergent synthesis proceeded through intermediates 2 and 3, formed enantioselectively from readily available starting materials and coupled through an aldol reaction followed by dehydration to afford stereoselectively the cyclopentenone alkylidene structural motif of the molecule.",10.1002/anie.201404917,2014-08-05,0.6461909588252356
Journal of Organic Chemistry,Total Synthesis of (+)-Isatisine A: Application of a Silicon-Directed Mukaiyama-Type [3 + 2]-Annulation,"Complete details of an asymmetric synthesis of (+)-isatisine A (1) are described. The synthesis highlights the use of a highly diastereoselective Mukaiyama-type [3 + 2]-annulation of allylsilane 5 with the unsaturated aldehyde 9a to assemble the functionalized tetrahydrofuran core of isatisine A. A convergent route to the framework of the natural product was established that employed a substrate-controlled indole coupling that was followed by a late-stage intramolecular copper(I)-mediated amidation to complete the assembly of the tetracyclic framework of (+)-isatisine A. In addition, the scope of the [3 + 2]-annulation was evaluated and enhanced utilizing diastereomeric allylsilanes anti-5 and syn-5 to establish an efficient route to stereochemically well-defined tetrahydrofurans.",10.1021/acs.joc.5b00051,2015-03-04,0.6461794768405926
Organic Letters,Total Synthesis of Sandresolide B and Amphilectolide,"The total synthesis of the diterpenoids sandresolide B and amphilectolide from a common furan building block is presented. Key steps include palladium-mediated carbonylation, lanthanide catalyzed ring closure, Myers alkylation, intramolecular Friedel-Crafts acylation, photooxygenation, and a Kornblum-DeLaMare rearrangement.",10.1021/ol403156r,2013-12-05,0.6461661534800325
Organic Process Research & Development,An Efficient and Impurity-Free Process for Telmisartan:  An Antihypertensive Drug,"Telmisartan ( 1 ), a substituted dibenzimidazole derivative, is an antihypertensive drug, essentially used to control blood pressure. An improved, cost-effective, and impurity-free process for telmisartan ( 1 ) suitable for large-scale production is described here by addressing various process development issues. The overall yield obtained from this newly developed process is around 50% (over five steps) compared to the literature reported process (21%, over eight steps).",10.1021/op060200g,2006-12-10,0.6461596062674442
Tetrahedron,The first practical asymmetric synthesis of R and S-Warfarin,,10.1016/0040-4039(96)01796-0,1996-11-01,0.6461469696761595
Tetrahedron,A practical asymmetric synthesis of carnitine,,10.1016/s0040-4039(00)80350-0,1988-01-01,0.6461469696761595
Organic Process Research & Development,An Improved Kilogram-Scale Synthesis of 2-Bromo-4-nitro-1<i>H</i>-imidazole: A Key Building Block of Nitroimidazole Drugs,"An efficient two-step method for the synthesis of 2-bromo-4-nitroimidazole, 6, a key building block for nitroimidazole drugs, has been developed. The synthesis involves dibromination of 4-nitroimidazole 10 followed by selective debromination using in situ reductive deiodination strategy. The reactions are facile, safe, and easy to scale up. The large-scale applicability of this improved method was tested by conducting the reactions on kilogram scale to produce the desired product in high yield and quality.",10.1021/op400095f,2013-08-15,0.6461087308614247
Tetrahedron,“An efficient synthesis of ethyl (R)-2-hydroxy-4-phenylbutyrate: A useful intermediate in the synthesis of converting enzymeinhibitors”,,10.1016/s0040-4039(00)80112-4,1988-01-01,0.6460941797080824
European Journal of Organic Chemistry,Towards the Total Synthesis of Pl‐3: Preparation of the Eastern Fragment through a Diastereoselective SmI<sub>2</sub>‐Mediated Reformatsky Reaction,"Abstract The jatrophane diterpene Pl‐3, isolated in 2003 from Euphorbia platyphyllos , is a structurally complex natural product with highly promising biological properties that include pronounced antiproliferative activity and the inhibition of the efflux‐pump activity of multidrug resistance p‐glycoprotein. Herein, the synthesis of the eastern fragment of Pl‐3 is outlined. The target compound is synthesized in nine synthetic operations in good overall yield, starting from readily available D ‐ribose. The key step in the preparation of the eastern part of Pl‐3 is a diastereoselective SmI 2 ‐mediated Reformatsky reaction. The proposed route is highly flexible and could also be applied to the synthesis of structurally related jatrophane diterpenes.",10.1002/ejoc.201300148,2013-03-07,0.6460924101012715
Synlett,Enantioselective Total Synthesis of Ligraminol D and Ligraminol E,"As a part of our ongoing research on the synthesis of bioactive constituents or molecules by using an organocatalytic approach, enantioselective total syntheses of ligraminol D and ligraminol E were achieved starting from a commercially available nonchiral aldehyde. Key steps in this synthesis were an asymmetric α-aminoxylation of an aldehyde and a Mitsunobu reaction.",10.1055/s-0039-1690249,2019-10-30,0.6460638217642339
Synthesis,Asymmetric Synthesis of the α-d-Galactosyl Ceramide KRN7000 via an Organocatalytic Aldol Reaction as Key Step,"The asymmetric synthesis of the antitumor and immunostimulatory α-d-galactosyl ceramide KRN7000 using a (R)-proline-catalyzed enantioselective aldol reaction as key step is described. The title compound is synthesized in thirteen linear steps with excellent stereoselectivity (de >98%, ee = 95%) employing the commercially available substrates 1-pentadecanal, 2,2-dimethyl-1,3-dioxan-5-one, hexacosanoic acid, and d-galactose.",10.1055/s-0029-1218844,2010-06-29,0.6460621570849674
Journal of the American Chemical Society,The Total Synthesis of Allosamidin. Expansions of the Methodology of Azaglycosylation Pursuant to the Total Synthesis of Allosamidin. A Surprising Enantiotopic Sense for a Lipase-Induced Deacetylation,"Allosamidin, recently isolated from mycelial extracts of Streptomyces sp. 1713, is a powerful and selective chitinase inhibitor. The total synthesis of allosamidin is described herein. The electric eel acetylcholinesterase-mediated enantioselective hydrolysis of ( trans, trans )-2-(benzyloxy)cyclopentene-1,3-diol diacetate accessed a monoacetyl derivative. Five additional steps produced a protected version of the aglycon (“allosamizoline”) sector of allosamidin. An allal derivative stereoselectively reacted with benzenesulfonamide in the presence of a halonium source to afford a 2β-halo-1α-sulfonamidohexose. Treatment of this product with a strong base generated an intermediate 1,2-sulfonylaziridine, which was trapped with a protected allal derivative to provide a disaccharide glycal. Reiteration of this scheme gave access to the required trisaccharide. Following deprotection, the total synthesis of allosamidin was accomplished. In addition, the method, with modification, gave access to several allosamidin analogs.",10.1021/ja960526c,1996-01-01,0.6460516090178472
Organic Letters,Total Synthesis of (+)- and (−)-Calycanthidine and Formal Synthesis of (−)-Idiospermuline via Key Pd(0)-Catalyzed Asymmetric Allylations,"We envisioned a novel asymmetric strategy to access unsymmetrically substituted dimeric 2-oxindoles [( S, S )- 8 and ( R, R )- 8 ] for the total synthesis of calycanthidine ( 4a ). The key to success is the development of efficient Pd(0)-catalyzed asymmetric sequential allylations [via a highly enantioselective [up to 94% enantiomeric excess (ee)] and diastereoselective (up to ∼13:1) process] of unsymmetrically protected dimeric 2-oxindoles at the 3,3′ position [such as ( S, S )- 8 and ( R, R )- 8 ]. Gratifyingly, a mixture of bis-ester (±)- 10a, ester-carbonates (±)- 10b and (±)- 10c, and bis-carbonate 10d could afford ( S, S )- 8 and ( R, R )- 8 in highly stereoselective fashion, thereby culminating in the total synthesis of (+)-calycanthidine [ ent -( 4a )] and (−)-calycanthidine ( 4a ). This effort also culminated in the formal total synthesis of idiospermuline ( 5 ).",10.1021/acs.orglett.4c03837,2024-12-05,0.6460027573643932
Synlett,A Facile Enantioselective Synthesis of the Dimeric Pyranonaphthoquinone Core of the Cardinalins,"The enantioselective synthesis of a dimeric pyranonaphthoquinone closely related to cardinalin 3 is described. Key steps include the Hauser-Kraus annulation between a cyanophthalide and a chiral enone to create the naphthalene skeleton, a Suzuki-Miyaura homocoupling of an aryl triflate to construct the biaryl bond and a double stereoselective lactol reduction to install the 1,3-cis stereo-chemistry of the pyran rings.",10.1055/s-2008-1042896,2008-03-20,0.6459596039232092
Journal of Organic Chemistry,Total Synthesis of Wedelolactone,"The total synthesis of wedelolactone, a naturally occurring direct inhibitor of IKK complex that can suppress LPS-induced caspase-11 expression, using a convergent synthetic approach, is described. The key steps involved in this synthesis include the palladium-catalyzed Sonogashira reaction and the palladium-catalyzed carbonylative annulation reaction. This approach allows access to diversified analogues of wedelolactone.",10.1021/jo030228f,2003-09-30,0.6459345669549983
Synlett,A Concise and Versatile Total Synthesis of All Stereoisomers of Tarchonanthuslactone,"We describe the versatile and concise total synthesis of all stereoisomers of tarchonanthuslactone from ( R )- or ( S )-3-hydroxybutyrate via eight steps. The key steps of the synthesis include a highly diastereoselective chelation-controlled Mukaiyama aldol reaction of a p -methoxybenzyl-protected aldehyde and a Yamaguchi lactonization of a δ-hydroxy- trans -α,β-unsaturated carboxylic acid.",10.1055/s-0034-1378784,2015-07-30,0.6459081338252439
Organic Letters,Total Synthesis of Hoiamide A Using an Evans–Tishchenko Reaction as a Key Step,The first total synthesis of neurotoxic cyclodepsipeptide hoiamide A ( 1 ) has been accomplished. The synthesis features the use of an Evans–Tishchenko fragment coupling between a five-stereogenic-center-containing β-hydroxyketone and a chiral aldehyde derived from threonine.,10.1021/acs.orglett.9b01735,2019-07-05,0.6458569721657569
Organic Letters,"Total Synthesis of Anibamine, a Novel Natural Product as a Chemokine Receptor CCR5 Antagonist","The total synthesis of anibamine, the first and only natural product known as a chemokine receptor CCR5 antagonist, is reported herein. Anibamine was synthesized from acetylacetone and cyanoacetamide in 10 steps.",10.1021/ol070748n,2007-04-21,0.6458493346050316
Organic Process Research & Development,Discovery and Development of an Efficient Process to Atovaquone,"The discovery and development of an efficient and more sustainable manufacturing route to the anti-pneumocystic agent atovaquone (2-((1 R,4 R )-4-(4-chlorophenyl)cyclohexyl)-3-hydroxynaphthalene-1,4-dione) 1 is described. The existing commercial route to atovaquone delivers a poor yield of product and uses expensive reagents. The new synthesis commences with readily available phthalic anhydride, which is converted to 1,4-isochromandione 5 and then to atovaquone 1 by reaction with 4-(4-chlorophenyl)cyclohexanecarboxylic acid 3 using key bromination, Rosenmund reduction, and rearrangement chemistries. Downstream processing to atovaquone is both high yielding and robust, and the resulting process has been demonstrated on 200-kg scale. The process is simple, uses cheap raw materials, and is more sustainable in that it avoids low-yielding silver-promoted chemistry and isomerisation procedures. It includes a robust, facile, and highly efficient procedure to 1,4-isochromandione 5, and routes to 4-(4-chlorophenyl)cyclohexanecarboxaldehyde 9 have also been developed, including a Rosenmund method that was demonstrated on pilot-plant scale. Also discussed are the route-derived impurities and processing amendments to control their formation.",10.1021/op300165q,2012-09-11,0.6458190921535393
Organic Process Research & Development,"Hetero Diels−Alder-Biocatalysis Approach for the Synthesis of (<i>S</i>)-3-[2-{(Methylsulfonyl) oxy}ethoxy]-4-(triphenylmethoxy)-1-butanol Methanesulfonate, a Key Intermediate for the Synthesis of the PKC Inhibitor LY333531<sup>1</sup>","A cost-effective and easily scaled-up process has been developed for the synthesis of ( S )-3-[2-{(methylsulfonyl)oxy}ethoxy]-4-(triphenylmethoxy)-1-butanol methanesulfonate, a key intermediate used in the synthesis of a protein kinase C inhibitor drug through a combination of hetero Diels−Alder and biocatalytic reactions. The Diels−Alder reaction between ethyl glyoxylate and butadiene was used to make racemic 2-ethoxycarbonyl-3,6-dihydro-2H-pyran. Treatment of the racemic ester with Bacillus lentus protease resulted in the selective hydrolysis of the R -enantiomer and yielded S -2-ethoxycarbonyl-3,6-dihydro-2H-pyran in excellent optical purity, which was reduced to S -3,6-dihdro-2H-pyran-2-yl methanol. Tritylation of this alcohol, followed by reductive ozonolysis and mesylation afforded the product in 10−15% overall yield and with >99% ee and chemical purity. Details of the process development work done on each step are given.",10.1021/op020202a,2002-03-16,0.6458168597297628
Organic Letters,Macrolactamization Approaches to Arylomycin Antibiotics Core,"Two practical entries to arylomycin antibiotics core structures are investigated. In route A, the activation of l-Hpg for the key macrolactamization step is achieved in 89% yield in the presence of unprotected phenol and amine functionalities. Alternatively, a propanephosphonic acid anhydride (T3P)-promoted coupling between thel-Tyr and l-Ala moieties in route B led to a facile macrolactamization in 68% yield with a marked reduction in competing oligomerization.",10.1021/acs.orglett.8b03603,2018-12-19,0.6458039288103542
Tetrahedron,Asymmetric synthesis VIII: Biogenetically patterned approach to the chiral total synthesis of (−)-pumiliotoxin-C,,10.1016/s0040-4039(00)84315-4,1986-01-01,0.6458018588935478
Tetrahedron,"Asymmetric synthesis of (R)-3,3-dimethyl-2-hydroxy-γ-butyrolactone en route to the formal synthesis of calcium D-pantothenate",,10.1016/s0040-4039(00)77292-3,1994-08-01,0.6457967171866213
Journal of Organic Chemistry,Synthesis of <i>N</i>-Methylpyrrole and <i>N</i>-Methylimidazole Amino Acids Suitable for Solid-Phase Synthesis,New and higher yielding synthetic routes to N-protected N-methylpyrrole and N-methylimidazole amino acids are introduced to circumvent difficulties associated with established schemes. Key steps in each synthesis include copper-mediated cross-coupling reaction to directly install a carbamate-protected 4-amine in the N-methylpyrrole derivative and effective nitration followed by a one-pot reduction/Boc protection of the amine in the synthesis of the N-Me-imidazole amino acid.,10.1021/jo048686r,2004-10-15,0.6457933986840448
Organic Letters,Synthesis of the GHIJKL Fragment of Gymnocin-B,"The GHIJKL fragment of gymnocin-B was synthesized using the oxiranyl anion strategy. The first highlight of the synthesis is the bromoketone cyclization reaction on the oxepane ring to construct the fused bisoxepane GH ring. The second key step is the introduction of the trans -4-hydroxy-3-methyloxepane J ring via addition of trimethylaluminum to a conjugated oxonium moiety, followed by diastereoselective epoxidation and regioselective reduction.",10.1021/acs.orglett.9b02502,2019-08-22,0.6457711088872922
Journal of Organic Chemistry,Concise Synthesis of Rodgersinol and Determination of the C-10 Absolute Configuration,"Rodgersinol was synthesized via seven linear steps in 31% overall yield, and the absolute configuration of the C-10 stereogenic center was elucidated. The key feature of the synthesis involves the efficient Cu(II)-mediated coupling of two aromatic moieties for the diaryl ether intermediate and the enantioselective construction of the hydroxypropyl substituent by a regio- and stereoselective methyl addition to the chiral aryloxiranes in an inversion manner.",10.1021/jo061980u,2006-12-14,0.6457655243514846
Angewandte Chemie International Edition,A Total Synthesis of Norhalichondrin B,"Four corners: The syntheses of four key building blocks for the total synthesis of norhalichondrin B (see structure) are described. The assembly of these subunits into the natural product is also reported. Key features of the synthesis are the use of the Achmatowicz oxidation/ionic hydrogenation for the synthesis of pyrans and pyranopyrans, and the application of tandem metathesis for the synthesis of pyranopyrans.",10.1002/anie.200806111,2009-02-11,0.6457587213768112
Angewandte Chemie International Edition,Access to Skipped Polyene Macrolides through Ring‐Closing Metathesis: Total Synthesis of the RNA Polymerase Inhibitor Ripostatin B,Rip-Roaring! A convergent total synthesis of antibiotic ripostatin B was developed. A key step in the synthesis is a metathesis reaction allowing for a ring closure to the labile doubly skipped triene macrolide.,10.1002/anie.201108692,2012-02-15,0.6457563194662422
Angewandte Chemie International Edition,"Total Synthesis of Carolacton, a Highly Potent Biofilm Inhibitor","Metals are the key players in the synthesis of caralacton, a strong inhibitor of bacterial biofilms. The total synthesis is based on several metal-mediated key transformations such as the Ley and the Duthaler–Hafner aldol reactions, the Marshall reaction and Breit's substitution, as well as the Nozaki–Hiyama–Kishi and Negishi–Fu CC coupling reactions.",10.1002/anie.201106762,2011-12-09,0.645754127630685
Organic Process Research & Development,"An Easy, Convenient, and Safe Process for the Synthesis of Lofexidine Hydrochloride","A very efficient, cost-effective, and easily scalable process for the synthesis of lofexidine hydrochloride ( 1 ), an alpha 2-adrenergic receptor agonist used for treating opioid withdrawal is presented. Process development allows the preparation of lofexidine hydrochloride ( 1 ) through a one-pot amidation/imidazoline ring formation reaction, starting from ethyl 2-(2,6-dichlorophenoxy)propionate ( 13 ) and ethylenediamine ( 5 ) by the action of titanium isopropoxide. The required intermediate ethyl 2-(2,6-dichlorophenoxy)propionate ( 13 ) can efficiently be obtained through O -alkylation of 2,6-dichlorophenol ( 2 ) with ethyl 2-chloropropionate ( 12 ) using potassium carbonate as an acid-scavenger agent.",10.1021/acs.oprd.0c00453,2021-07-27,0.6457541068089593
Synlett,Synthesis of Novel Allocolchicine Analogues with a Pyridine C-Ring through Intermolecular Vollhardt Diyne-Nitrile Cyclotrimerization,"A short synthesis of new allocolchicinoids with a pyridine C-ring and an oxa-B-ring was developed exploiting a cobalt-catalyzed intermolecular [2+2+2] cycloaddition (diyne-nitrile cyclotrimerization). Starting from readily accessible 3,4,5-trimethoxy­benzaldehyde or 3,4,5-trimethoxyacetophenone, the (racemic) target compounds were regioselectively obtained in 15-20% overall yield (five steps).",10.1055/s-0030-1258512,2010-07-22,0.6457374069632834
Organic Letters,"Synthesis of Novel Imidazo[1,2-<i>a</i>]pyridines with Potent Activity against Herpesviruses","[reaction: see text] Synthesis of a novel imidazopyridine with potent activity against herpes simplex viruses is presented. Several synthetic approaches that describe the introduction of a C-3 pyrimidine substituent on the imidazopyridine core via construction of the pyrimidine or Stille coupling are outlined. Methodology for efficient installation of C-8 amine substituents was developed. The outlined strategies provide a high-yielding, scalable route that is amenable to rapid analogue synthesis.",10.1021/ol0343616,2003-03-28,0.6457323113913748
Organic Letters,Total Synthesis of (+)-Dactylolide,"[reaction: see text] The development of an approach leading to the total synthesis of dactylolide is described. The key features of this route include a catalytic asymmetric allylation, a diastereoselective pyran annulation, and a Horner-Wadsworth-Emmons macrocyclization.",10.1021/ol051040g,2005-06-07,0.6457228066755184
Journal of the American Chemical Society,Total Synthesis of Bryostatin 9,"The total synthesis of bryostatin 9 was accomplished using a uniquely step-economical and convergent Prins-driven macrocyclization strategy. At 25 linear and 42 total steps, this is currently the most concise and convergent synthesis of a potent bryostatin.",10.1021/ja203034k,2011-05-27,0.6457224955155999
Journal of Organic Chemistry,(.+-.)-Carpesiolin: total synthesis and structural determination,"The total synthesis of the helenanolide (+/-)-carpesiolin starting from the key trans-fused hydroazulenic ketone 1 is described. Salient features of the sequence invlove the introduction of the α configuration at C-10 via catalytic hydrogenation (9), the stereoselective reduction of cycloheptenone 14, obtained from 9 in five steps, to yield exclusively the α-orented allylic alcohol 16 and its conversion into lactone 19 via stereodirected expoxidation, regioselective epoxide ring opening by dilithioacetate, and selective ring closure to the C-7, C-8 oriented γ-lactone. 19 is further transformed into the title compound. This total synthesis also enables the full structural determination of (+/-)-carpesiolin as 6.",10.1021/jo00393a020,1979-12-01,0.6457144464307023
Synlett,"Superacid Activated Condensation of Parabanic Acid and Derivatives with Arenes. A New Synthesis of Phenytoin and 5,5-Diarylhydantoins","All articles of this category A new synthetic route in phenytoin and 5,5-diarylhydantoins is reported. Parabanic acid is converted to the 5,5-diarylhydantoins (65-98% yield) from CF 3 SO 3 H and arenes. Deuterium substituted produts are prepared in high yield from parabanic acid, CF 3 SO 3 D, and deuterated arenes. phenytoin - hydantoin - heterocycle - superacid - electrophile",10.1055/s-1998-1811,1998-08-01,0.6456648315107519
Tetrahedron,A novel synthetic route to 7-substituted derivatives of the antitumor agent LY231514 (MTA),,10.1016/s0040-4039(99)00959-4,1999-07-01,0.6456575389712481
Angewandte Chemie International Edition,Asymmetric Total Synthesis of Mycoleptodiscin A,"The first total synthesis of mycoleptodiscin A, a structurally unusual indolosesquiterpenoid possessing an ortho-benzoquinone motif, has been accomplished. A sulfone alkylation coupled two readily available fragments to give an aryl triene intermediate. The tetracyclic core of the molecule was assembled through a highly enantioselective iridium-catalyzed polyene cyclization. The benzylic homologation was achieved by a cationic cyanation. The indole motif was constructed via a copper-mediated intramolecular C-N bond formation at a late stage.",10.1002/anie.201501021,2015-04-23,0.6456554321909944
Journal of Organic Chemistry,Regioselective Synthesis of α-Methyl 2-Methyleneglutarate via a Novel Lactonization−Elimination Rearrangement,"[reaction: see text] A facile route to the alpha-methyl ester of 2-methyleneglutarate via a three-step sequence from 3-hydroxymethylcyclopentene is described. Regioselective formation of the monoacid from a diester precursor proceeds via a novel fluoride-mediated, tandem deprotection/rearrangement of O-silyl 2-(hydroxymethyl)dimethylglutarate.",10.1021/jo051854a,2005-11-25,0.6456377752415189
Tetrahedron,"Electrophile-induced cyclization of γ,δ-alkenylimines as a synthetic route to pyrrolidines and piperidines",,10.1016/s0040-4039(00)73197-2,1994-03-01,0.6456277941831694
Organic Process Research & Development,Sustainable Manufacturing of <i>trans</i>-4-Trifluoromethyl-<scp>l</scp>-proline via Stereochemical Editing: A Combined In Silico and Experimental Approach,"Ibuzatrelvir ( 1 ) is a second-generation, orally bioavailable, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease inhibitor clinical candidate. Herein, we report the implementation of an in silico and high-throughput experimentation strategy leading to the identification of a rapid, efficient, and sustainable route to trans -4-trifluoromethyl- l -proline ( 2 ), a key building block for ibuzatrelvir. This novel synthetic route features a key stereochemical editing step to enable an efficient and scalable protocol that operates under mild conditions with high stereoselectivity, providing effective access to more than 235 kg of trans -4-trifluoromethyl- l -proline 2 in a five-step synthetic sequence from readily available starting materials.",10.1021/acs.oprd.4c00202,2024-07-31,0.6456267418224968
European Journal of Organic Chemistry,Total Synthesis of Leukotrienes from Butadiene,"The total synthesis of leukotrienes has been achieved starting from butadiene by a palladium-catalyzed telomerization at room temperature. A Sharpless catalytic asymmetric epoxidation generated the asymmetric centers with >94% ee. Simple transformations of the key intermediate 15 produced the leukotrienes LTA4 methyl ester (4), LTC4 (1), LTD4 (2) and LTE4 (3), as well as (14S,15S)-LTA4 methyl ester (24) and the novel [2H2]-LTA4 methyl ester (28). The use of the opposite chiral director in the Sharpless catalytic asymmetric epoxidation gave the key intermediate 15a that has been used in the synthesis of the double epimers of the leukotrienes as well as LTB4.",10.1002/1099-0690(200009)2000:17<2991::aid-ejoc2991>3.0.co;2-h,2000-09-01,0.645623889217091
Organic Letters,Synthesis of the Griseusin B Framework via a One-Pot Annulation–Methylation–Double Deprotection–Spirocyclization Sequence,A highly convergent synthesis of the griseusin B scaffold is described. The key step involves an efficient one-pot Hauser-Kraus annulation-methylation-double deprotection-spirocyclization sequence that directly affords the target parent tetracyclic ring system.,10.1021/ol400686f,2013-04-05,0.6455979874384069
Synlett,The Total Synthesis of (+)-Palitantin,"All articles of this category An asymmetric synthesis of (+)-palitantin [ 1 ;(2 R ,3 R ,5 S ,6 R )-5-(1,3-heptadienyl) -2,3-dihydroxy-6-hydroxymethyl-cyclohexanone] is described, starting from the homochiral alcohol (-) -3 [(1 S ,2 S ,3 R ) -2,3-isopropylidenedioxycyclohexanol], obtained via lipase-mediated resolution. Key steps include a regioselective dehydration and stereoselective cuprate addition.",10.1055/s-1992-21262,1992-01-01,0.6455926289930978
Journal of Organic Chemistry,Stereoselective Synthesis of an Active Metabolite of the Potent PI3 Kinase Inhibitor PKI-179,"The synthesis and stereochemical determination of 1-(4-(4-((1R,5R,6R)-6-hydroxy-3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-6-morpholino-1,3,5-triazin-2-yl)phenyl)-3-(pyridin-4-yl)urea (2), an active metabolite of the potent PI3 kinase inhibitor PKI-179 (1), is described. Stereospecific hydroboration of the double bond of 2,5-dihydro-1H-pyrrole 8 gave the 2,3-trans alcohol 9 exclusively. The configuration of the 3-hydroxyl group in 9 was inverted by an oxidation and stereoselective reduction sequence to give the corresponding 2,3-cis isomer 23. Both exo (21) and endo (27) isomers of the metabolite 2 were prepared via a practical synthetic route from 9 and 23, respectively, and the stereochemistry of 2 was determined to be endo. The endo isomer (27) was separated into two enantiomers 28 and 29 by chiral HPLC. Compound 2 was found to be enantiomerically pure and identical to the enantiomer 28. The absolute stereochemistry of the enantiomer 28 was determined by Mosher's method, thus establishing the stereochemistry of the active metabolite 2.",10.1021/jo9026269,2010-01-29,0.6455856130588669
Organic Letters,Total Synthesis of a Linear Tetrasaccharide Repeating Unit of <i>Vibrio vulnificus</i> MO6-24,"Herein, we report the total synthesis of a linear, conjugation-ready, tetrasaccharide repeating unit of Vibrio vulnificus MO6-24, which is composed of rare amino sugars such as l -quinovosamine and d -galactosamine uronic acid. The key challenges addressed here are the synthesis of rare deoxy amino sugars, installation of consecutive 1,2- cis glycosidic linkages, and late-stage oxidation. Total synthesis of the target molecule was completed via a longest linear sequence of 29 steps in an overall yield of 0.7% starting from l -rhamnose.",10.1021/acs.orglett.3c02872,2023-09-27,0.6455198918354216
Organic Process Research & Development,"A Practical Synthesis of the RAR<sub>γ</sub> Agonist, BMS-270394","A novel synthesis of 1 (BMS-270394), a nuclear retinoic acid receptor (RARγ) agonist, is reported. The synthesis includes an enantioselective reduction of α-ketoacid 4 to the corresponding chiral α-hydroxy acid 7 using a NaBH 4 / l -tartaric acid mixture and a novel coupling between 7 and an electron-deficient aniline 11 which was activated via N-sulfinyl derivative 15 to form chiral α-hydroxy amide 16 . The synthesis was completed by a racemization-free hydrolysis of 16 to the corresponding α-hydroxy amidoacid 1 using KOSiMe 3 in acetonitrile.",10.1021/op0202134,2002-07-24,0.6454859303528393
Synlett,An Efficient Total Synthesis of Isodrimeninol from Zamoranic Acid,"All articles of this category An efficient total synthesis of isodrimeninol ( 1 ) has been achieved from zamoranic acid ( 3 ) employing a regioselective Lewis acid mediated elimination-isomerisation as the key step. Following oxidative cleavage of the resulting conjugated diene to the methyl ketone, standard manipulations allowed the synthesis of allylic alcohols 10 which, after a highly diastereoselective epoxidation and subsequent lactonisation, allowed the synthesis of the natural product in 11 steps and 56% overall yield. regioselective acid-catalysed elimination - γ -lactones - δ -lactones - bioactive drimanes - diastereoselective epoxidation",10.1055/s-2000-6575,2000-01-01,0.6454700558466687
Organic Letters,"Syntheses of Chloroisosulochrin and Isosulochrin and Biomimetic Elaboration to Maldoxin, Maldoxone, Dihydromaldoxin, and Dechlorodihydromaldoxin","An efficient synthesis of chloroisosulochrin was accomplished using a novel ortho-selective chlorination of a phenol with sulfuryl chloride and 2,2,6,6-tetramethylpiperidine as the key step. Further elaboration by a biomimetic route converted chloroisosulochrin to dihydromaldoxin, maldoxone (lactone formed by dehydration of dihydromaldoxin), and maldoxin and isosulochrin to dechlorodihydromaldoxin and dechloromaldoxin.",10.1021/ol201561w,2011-07-27,0.6454561321637371
Tetrahedron,"Synthesis of (2R,4S,5S)-5-acetamido-4-hydroxy-pipecolinic acid as a potential inhibitor of sialidases",,10.1016/s0040-4039(00)96878-3,1987-01-01,0.6454558013578088
Angewandte Chemie International Edition,Expeditious and Divergent Total Syntheses of Aspidosperma Alkaloids Exploiting Iridium(I)‐Catalyzed Generation of Reactive Enamine Intermediates,"A new approach for the divergent total syntheses of (±)-vincaminorine, (±)-N-methylquebrachamine, (±)-quebrachamine, (±)-minovine and (±)-vincadifformine, each in less than 10 linear steps starting from a single δ-lactam building block, is reported. Key to our route design is the late-stage generation of reactive enamine functionality from stable indole-linked δ-lactams via a highly chemoselective iridium(I)-catalyzed reduction. The efficiently formed secodine intermediates subsequently undergo either a formal Diels-Alder cycloaddition or a competitive Michael addition/reduction to access aspidosperma-type alkaloids in excellent diastereoselectivities. Product selectivity could be controlled by changing the indole N-protecting group in the reductive cyclization precursors. An asymmetric variant of this synthetic strategy for the synthesis of (+)-20-epi-ibophyllidine is also described.",10.1002/anie.201605503,2016-09-23,0.6454523849037246
Synlett,Total Synthesis of (±)-Phaeocaulisin D,"Abstract The tropone sesquiterpene phaeocaulisin D, isolated from the rhizomes of Curcuma phaeocaulis, has previously been shown to inhibit nitric oxide production in macrophages. A total synthesis of phaeocaulisin D was accomplished by using an intramolecular cyclization–dearomatization as a key step. The highlights of the synthesis are effective formation of the 5–7 fused tropone system, and selective methylation of a late-stage intermediate.",10.1055/a-1326-9148,2020-12-01,0.6454520587037607
Journal of Organic Chemistry,Northern–Southern Route to Synthetic Bacteriochlorins,"A new route to bacteriochlorins via Northern–Southern (N-S) self-condensation of a dihydrodipyrrin–acetal complements a prior Eastern–Western (E-W) route. Each bacteriochlorin was prepared in five steps from an α-halopyrrole and a 2,2-dimethylpent-4-ynoic acid. The first three steps follow Jacobi’s synthesis of dihydrodipyrrins: Pd-mediated coupling to form a lactone–pyrrole, Petasis reagent treatment for methenylation, and Paal–Knorr type ring closure to form the 1,2,2-trimethyl-substituted dihydrodipyrrin. Subsequent steps entail conversion of the 1-methyl group to the 1-(dimethoxymethyl) unit and acid-catalyzed self-condensation of the resulting dihydrodipyrrin–acetal. The essential differences between the N-S and E-W routes lie in (1) the location of the gem -dimethyl group (with respect to the 1-acetal unit) at the 2- versus 3-position in the dihydrodipyrrin–acetals, respectively, (2) the method of synthesis of the dihydrodipyrrins, and consequently (3) access to diverse substituted bacteriochlorins including those with substituents at the meso-positions. Ten new bacteriochlorins bearing 0–6 total aryl, alkyl, and carboethoxy substituents at the β-pyrrole and/or meso-positions have been prepared, with yields of macrocycle formation of up to 39%. Four single-crystal X-ray structures (two intermediates, two bacteriochlorins) were determined. The bacteriochlorins exhibit characteristic bacteriochlorophyll-like absorption spectra, including a Q y band in the region 713–760 nm.",10.1021/acs.joc.6b02334,2016-11-21,0.645446918966295
Organic Process Research & Development,"Development of a Suitable Process for the Preparation of a TNF-α Converting Enzyme Inhibitor, WAY-281418","A suitable process for the preparation of kilogram quantities of a TNF-α converting enzyme (TACE) inhibitor (WAY-281418) was developed using isatin 13 as starting material and an efficient coupling step for the formation of sulfonamide 8 in a 15% overall yield. Process preparation of (+)-(1 S,2 R )-2-aminocyclopentane-1-carboxylic acid ( 7, (+)-cispentacin), a chiral component for WAY-281418, was successfully scaled up via an asymmetric hydrogenation reaction. Crystallization allowed the isolation of all intermediates and the final product 9 .",10.1021/op800090s,2008-09-09,0.6454418616601788
Synthesis,Scalable and Straightforward Synthesis of a 2-Alkyl-7-Arylbenzothiophene as a GPR52 Agonist via a Hemithioindigo Derivative,"A simple and efficient procedure has been developed for the synthesis of the GPR52 agonist N -(2-amino-2-oxoethyl)-3-{4-fluoro-2-[3-(trifluoromethyl)benzyl]-1-benzothien-7-yl}benzamide. The benzo­thiophene unit was directly constructed by reduction of a hemithioindigo derivative prepared by an intramolecular Friedel–Crafts cyclization of (phenylsulfanyl)acetic acid, followed by dehydrative benzylidene formation.",10.1055/s-0034-1378746,2015-08-11,0.6454342373816337
Synthesis,Synthesis of the Tripeptide Antibiotic Resormycin,"A short and efficient synthesis of resormycin, a metabolite of Streptomyces platensis MJ953-SF5 with herbicidal and antifungal activity, is described. The key step in our synthetic approach is a late-stage stereospecific dehydration of a β-hydroxy amino acid to install the Z-olefin. Because of the modular nature of the synthesis, access to analogues for biological evaluation is readily available.",10.1055/s-0036-1588553,2017-08-28,0.6454119734141
Organic Process Research & Development,Stereoselective Synthesis of ABBV-992 Enabled by a Flow Diazotization and a Partial Reduction of a Pyridone,"Bruton’s tyrosine kinase (BTK) is involved in B-cell receptor signaling and has been clinically validated as a target by small molecule inhibition for the treatment of a variety of cancers. ABBV-992 ( 1 ) was identified as a novel, potent, selective BTK inhibitor and advanced to Phase I clinical trials. An enantioselective synthesis of 1 was developed and scaled to provide 63 g for preclinical characterization. The route features a diazotization enabled by flow chemistry, a novel, selective partial reduction of a pyridone, a stereoselective Ellman imine reduction, and an improved acrylamide formation using 3-chloropropionyl chloride in a masked acrylate strategy.",10.1021/acs.oprd.4c00077,2024-07-12,0.6454038447841307
Journal of the American Chemical Society,Total Synthesis of (+)-Aberrarone,"The structurally intriguing diterpene (+)-aberrarone has been assembled in only 12 steps from the commercially available ( S, S )-carveol without protecting group manipulations. This concise synthesis features a Cu-catalyzed asymmetric hydroboration to generate the chiral methyl group, a Ni-catalyzed reductive coupling to link two fragments, and a Mn-mediated radical cascade cyclization to construct the triquinane system.",10.1021/jacs.3c02511,2023-04-21,0.6453973082578301
Tetrahedron,"Schizostatin, a potent squalene synthase inhibitor from Schizophyllum commune: Isolation, structure elucidation, and total synthesis",,10.1016/0040-4039(95)01265-j,1995-08-01,0.6453623187132053
Journal of Organic Chemistry,Total Synthesis of an Antitumor Agent RA-VII via an Efficient Preparation of Cycloisodityrosine,"Details of efficient syntheses of (9 S,12 S )-cycloisodityrosine ( 6 ) and a concise total synthesis of RA-VII ( 1 ) were described. An intramolecular S N Ar-based cycloetherification reaction was employed as the key ring-closure step for construction of the illusive 14-membered m,p -cyclophane. Treatment of methyl N -[ N -( tert -butyloxycarbonyl)- l -(3-hydroxy-4-methoxyphenylalanyl]- l -4-fluoro-3-nitrophenylalaninate ((9 S,12 S )- 10 ) with potassium carbonate in DMSO at room temperature provided a mixture of two atropdiastereomers 20a and 20b in 75% yield that were transformed into cycloisodityrosine 6 in good overall yield. Furthermore, a size-selective ring-forming process was established for methyl N -[ N -( tert -butyloxycarbonyl)- l -(3,4-dihydroxyphenylalanyl)]- l -4-fluoro-3-nitrophenylalaninate ((9 S,12 S )- 11 ). Thus, cyclization of 11 (K 2 CO 3, DMSO, rt), followed by in situ methylation, gave exclusively the 14-membered m,p- cyclphane 20a and 20b without competitive formation of the alternative 15-membered p,p -cyclophane. The selective ring-forming process allowed us to develop one of the shortest and the most efficient synthesis of cycloisodityrosine to date. Computational studies have shown that it was the elimination, but not the addition, step that determined the ring-size selectivity observed in the cyclization of substrate 11 . Coupling of 6 with l - N -Boc-Ala ( 51 ) proceeded efficiently to provide the corresponding tripeptide 52 that, after removal of the N -Boc function, was allowed to react with another tripeptide 53 to afford the hexapeptide 50 in good overall yield. Saponification followed by liberation of amino function from 50 gave the seco -acid, whose cyclization (DPPA, DMF, NaHCO 3 ) afforded the natural product RA-VII ( 1 ).",10.1021/jo990432w,1999-07-28,0.6453618739889071
Organic Process Research & Development,An Efficient and Cost-Effective Synthesis of 3-Ethoxy-4-ethoxycarbonyl-phenylacetic Acid:  A Key Acid Synthon of Repaglinide,"This report describes an efficient and commercially viable synthesis of 3-ethoxy-4-ethoxy-carbonyl-phenylacetic acid ( 1 ), a key intermediate for the preparation of repaglinide, an oral hypoglycemic agent, from 2-hydroxy-4-methylbenzoic acid in two steps. Thus, 2-hydroxy-4-methylbenzoic acid was first alkylated with ethyl bromide in a polar aprotic solvent and in the presence of an inorganic base to afford ethyl 2-ethoxy-4-methylbenzoate; deprotonation with lithium diisopropylamide (LDA) and quenching the resulting carbanion with carbon dioxide provided the desired compound with improved yield and excellent purity. This procedure is significantly better than a previously published synthesis which involves five steps and requires use of expensive and hazardous reagents.",10.1021/op015513k,2002-01-26,0.6453293195172272
Tetrahedron,The reaction of trialkylboranes with α-methoxyvinyllithium a novel route to dialkylmethylcarbinols,,10.1016/0040-4039(76)80028-7,1976-06-01,0.6453041703336783
Tetrahedron,"Vilsmeier-haack reaction of 2H-1,4-benzoxazin-3-one: novel route for condensed benzoxazines",,10.1016/s0040-4039(01)96426-3,1971-01-01,0.6453041703336783
Synthesis,"A Novel Route to 1-(Azidoalkyl)-tetrazoles by ""Hassner-Ritter"" Reaction",,10.1055/s-1973-22212,1973-01-01,0.6453041703336783
Synthesis,De Novo Synthesis of a Potent LIMK1 Inhibitor,"A potent LIMK1 inhibitor, BMS4, was synthesised in six steps starting from pyrazine-2-carboximidamide, offering a significant improvement over current methods available in the literature.",10.1055/s-0029-1219230,2010-01-20,0.6453038639531931
Organic Letters,Highly Efficient Asymmetric Synthesis of Fluvirucinine A<sub>1</sub> via Zr-Catalyzed Asymmetric Carboalumination of Alkenes (ZACA)−Lipase-Catalyzed Acetylation Tandem Process,"ZACA-lipase-catalyzed acetylation tandem process has been shown to proceed satisfactorily with either TBS-protected 4-penten-1-ol or 3-buten-1-ol to provide the corresponding enantiomerically pure (R)-2-ethyl-1-alkanols. Either (R)-5 or (R)-6 was converted to 3 in seven steps. The other fragment 4 was synthesized in nine steps from (-)-(S)-citronellol. Conversion of 3 and 4 into 99% pure fluvirucinine A1 was achieved in four steps via amidation-ring closing metathesis, the overall yield in the longest linear sequence being 34% (13 steps).",10.1021/ol702272d,2007-12-13,0.6453033338575157
Tetrahedron,Synthesis of ethyl (±1)-(e)-5-(4- and 5-(3-hydroxy-1-octenyl)-1-methyl-2-imidazolin-2-yl)-5-thia pentanoates,,10.1016/s0040-4039(01)80012-5,1984-01-01,0.6453019568777953
Synlett,Synthetic Studies on Oligomycins. Synthesis of the Oligomycin B Polypropionate Portion,"All articles of this category The synthesis of the oligomycin B polypropionate (C1-C18) portion was achieved by an aldol coupling between the C3-C9 aldehyde and the C10-C16 ketone. A crotylstannane addition, the Brown's crotylboration, and a metalated methoxyallene addition were the key steps for the syntheses of these subunits.",10.1055/s-1994-22941,1994-01-01,0.6452922374675168
Tetrahedron,"A facile enzymatic synthesis of galβ1,3glucal: a key intermediate for the synthesis of Lea and sialyl Lea",,10.1016/s0040-4039(00)74231-6,1992-07-01,0.6452905083543357
Synthesis,Enantioselective Total Synthesis of (+)- and (-)-Vittatalactone,"The asymmetric total synthesis of both enantiomers of (+)- and (-)-vittatalactone has been achieved using a desymmetrization strategy to create three methyl chiral centers. The key steps in these total syntheses are Myers asymmetric alkylation, copper-­catalyzed alkylation, 2,2,6,6-tetramethyl-1-piperidinyloxyl-(diacet­oxyiodo)benzene [TEMPO-PhI(OAc2)] promoted oxidation and p-toluenesulfonyl chloride mediated lactonization. The products are obtained in good overall yields employing linear synthetic sequences.",10.1055/s-0031-1290155,2012-01-25,0.6452711507097435
Journal of the American Chemical Society,Total Synthesis of the Ristocetin Aglycon,"The first total synthesis of the ristocetin aglycon is described employing a modular and highly convergent strategy. An effective 12-step (12% overall) synthesis of the ABCD ring system 3 from its amino acid subunits sequentially features an intramolecular aromatic nucleophilic substitution reaction for formation of the diaryl ether and closure of the 16-membered CD ring system (65%), a respectively diastereoselective (3:1, 86%) Suzuki coupling for installation of the AB biaryl linkage on which the atropisomer stereochemistry can be further thermally adjusted, and an effective macrolactamization (51%) for closure of the 12-membered AB ring system. A similarly effective 13-step (14% overall) synthesis of the 14-membered EFG ring system 4 was implemented employing a room-temperature intermolecular S(N)Ar reaction of an o-fluoronitroaromatic for formation of the FG diaryl ether (69%) and a key macrolactamization (92%) with formation of the amide linking residues 1 and 2. The two key fragments 3 and 4 were coupled, and the remaining 16-membered DE ring system was closed via diaryl ether formation to provide the ristocetin tetracyclic ring system (15 steps, 8% overall) enlisting an unusually facile (25 degrees C, 8 h, DMF, >/=95%) and diastereoselective (>/=15:1) aromatic nucleophilic substitution reaction that benefits from substrate preorganization.",10.1021/ja039795a,2004-03-13,0.6452692594403785
Journal of Organic Chemistry,Synthesis of Novel Apio Carbocyclic Nucleoside Analogues as Selective A<sub>3</sub> Adenosine Receptor Agonists,"On the basis of the biological activity of neplanocin A and apio-dideoxyadenosine (apio-ddA), novel apio-neplanocin A analogues 5a-d, combining the properties of two nucleosides, were stereoselectively synthesized. The apio moiety of the target nucleosides 5a-d was stereoselectively introduced by treating lactol 10 with 37% formaldehyde in the presence of potassium carbonate. The carbasugar moiety of neplanocin A was successively built by exposing diene 12 on a Grubbs catalyst in methylene chloride. The final nucleosides 5a-d were synthesized from the condensation of the glycosyl donor 14 with nucleic bases under the standard Mitsunobu conditions. Similarly, apio-aristeromycin 6 and (N)-apio-methanocarbaadenosine 7 were derived from the common intermediate 13 using catalytic hydrogenation and Simmons-Smith cyclopropanation as key steps. All of the final nucleosides 5a-d, 6, and 7 did not show significant inhibitory activity against S-adenosylhomocysteine hydrolase (SAH) up to 100 muM, maybe due to the absence of the secondary hydroxyl group at the C3'-position, which should be oxidized by cofactor-bound NAD(+). However, apio-neplanocin A (5a) showed potent and highly selective binding affinity (K(i) = 628 +/- 69 nM) at the A(3) adenosine receptor without any binding affinity at the A(1) and A(2A) adenosine receptors. In conclusion, we have first developed novel carbocyclic nucleosides with unnatural apio-carbasugars using stereoselective hydroxymethylation and RCM reaction and also discovered a new template of human A(3) adenosine receptor agonist, which play a great role in developing new A(3) adenosine receptor agonist as well as in identifying the binding site of the receptor.",10.1021/jo0503207,2005-05-17,0.6452672697521391
Organic Process Research & Development,Development of a Scalable Process for the PPAR-α Agonist GW641597X Incorporating Baeyer–Villiger Chemistry and Retrospective ICH M7 Assessment,"The development of the synthetic process to the PPAR-α receptor antagonist 5-((4-( tert -butoxy)-3-methylphenoxy)methyl)-3-(4-( tert -butyl)phenyl)-1,2,4-oxadiazole (GW641597X) 1 is described. The discussion ranges from the initial supply route, used to deliver early batches for preliminary safety studies to enable dosing in man, to an efficient manufacturing route, which delivered 35 kg of drug substance following on from a pilot plant campaign. The process includes a key oxidative Baeyer–Villiger reaction, where process development identified sodium perborate in acetic acid as a safer alternative to m -chloroperoxybenzoic acid that was used in the initial supply route. Described within is a discussion of impurities, how they are formed, and the process modifications incorporated to either reduce or remove them. There is also a discussion of potential mutagenic impurities within the synthetic process and a retrospective evaluation using ICH M7 control options. Finally, an alternative route to GW641597X is described, which offers the advantage that all intermediates are crystalline facilitating material handling, offering purification opportunities through recrystallization if required, and potentially providing greater controls for the process. This new route was also retrospectively assessed using ICH M7 option controls and highlighted that ICH M7 option 4 controls can be implemented even with excess mutagenic reagents being introduced near to the drug substance as long as the science for its purging is well understood.",10.1021/acs.oprd.9b00385,2020-02-18,0.6452665162064656
Organic Letters,Total Synthesis of Nannocystin Ax,The total synthesis of nannocystin Ax in an overall yield of 11% with 14 steps as the longest linear sequence is reported. Nannocystin Ax is a cytotoxic 21-membered depsipeptide and was isolated from the myxobacterial genus Nannocystis sp. The synthesis uses a vinylogous Horner-Wadsworth-Emmons reaction (HWE) and a vinylogous Mukaiyama aldol reaction (VMAR) as the key steps for the construction of the polyketide fragment. The macrocycle was closed via a macrolactamization reaction using COMU.,10.1021/acs.orglett.7b02112,2017-08-15,0.6452653710971036
Organic Process Research & Development,Atom-Economical and Scalable Asymmetric Synthesis of Daridorexant Key Starting Material ( <i>S</i> )-2-Methylproline via the Memory of Chirality,"α-Methylproline is a key starting material (KSM) for important drugs, such as Daridorexant, Veliparib, Trofinetide, Enlicitide chloride, and Usnoflast. A practical and scalable asymmetric synthesis of ( S )-2-methylproline and its derivatives has been disclosed here using a diketopiperazine intermediate-based strategy that leverages the memory of chirality. Commencing from an inexpensive starting material, l -proline, it proceeds through dimerization and alkylation, followed by hydrolysis under mild conditions, avoiding column chromatography to furnish enantiomerically pure ( S )-2-methylproline.HCl, which was also converted to ( S )-Boc-2-methylproline and ( S )-2-methylproline methyl ester.HCl. In contrast to prior multistep approaches, which rely on expensive chiral auxiliaries and hazardous reagents, this concise three-step route offers operational simplicity, scalability, and superior stereochemical control, making it an attractive method for the synthesis of proline-derived building blocks for peptidomimetics and pharmaceutical applications.",10.1021/acs.oprd.5c00366,2025-11-14,0.6452489960128936
Tetrahedron,A new synthetic route to unsymmetric P-chirogenic bisphosphine ligands,,10.1016/s0040-4039(00)02192-4,2001-02-01,0.6452459730023858
Synthesis,Scalable Total Synthesis of Piceatannol-3′-O-β-d-glucopyranoside and the 4′-Methoxy Congener Thereof: An Early Stage Glycosylation Strategy,"Abstract Scalable syntheses of piceatannol-3′-O-β-d-glucopyranoside and the 4′-methoxy congener thereof were achieved. This route features an early implemented Fischer-like glycosylation reaction, a regioselective iodination of phenolic glycoside under strongly acidic conditions, a highly telescoped route to access the styrene derivative, and a key Mizoroki–Heck reaction to render the desired coupled products in high overall yield.",10.1055/a-1639-0648,2021-09-07,0.6452238681368591
European Journal of Organic Chemistry,"Simple Synthesis of (±)-Stigmolone (8-Hydroxy-2,5,8-trimethyl-4-nonanone), the Pheromone ofStigmatella aurantiaca","The racemic myxobacterial pheromone (±)-1 (stigmolone), which induces the formation of the fruiting body of Stigmatellaaurantiaca, was synthesized from methyl isobutyl ketone (2) in 48% overall yield in four steps",10.1002/(sici)1099-0690(199905)1999:5<979::aid-ejoc979>3.0.co;2-c,1999-05-01,0.6452209436462706
Tetrahedron,"Total synthesis of OF4949-III, a novel inhibitor of aminopeptidase B",,10.1016/s0040-4039(00)80149-5,1988-01-01,0.6452100383853574
Organic Letters,"Total Synthesis of 6-Amino-2,6-dideoxy-α-Kdo from <scp>d</scp>-Mannose","3-Deoxy- d - manno -oct-2-ulosonic acid (Kdo) biosynthetic pathway is a promising target in antibacterial drug discovery. Herein, we report the total synthesis of 6-amino-2,6-dideoxy-α-Kdo in 15 steps from d -mannose as a potential inhibitor of Kdo-processing enzymes. Key steps of the synthetic sequence involve a Horner–Wadsworth–Emmons reaction for the two-carbon chain homologation followed by either a 6- exo-trig Pd-catalyzed reductive cyclization or a tandem Staudinger/aza-Wittig reaction with concomitant α-iminoester reduction, enabling the α-stereoselective formation of the Kdo-like six-membered azacyclic ring.",10.1021/acs.orglett.0c01847,2020-07-14,0.6451938757185826
European Journal of Organic Chemistry,An Efficient Formal Total Synthesis of Cladosporin,"Abstract A highly diasteroselective and efficient approach for the formal total synthesis of cladosporin is described. Cross‐metathesis, iodocyclization to construct the trans ‐2,6‐disubstituted dihydropyran ring system, and an Alder–Rickert reaction to form the aromatic ring were used as the key steps.",10.1002/ejoc.201300053,2013-03-19,0.6451906127253618
Tetrahedron,A convenient allylsilane-N-acyliminium route toward 5-alkylindolizidines. Diastereoselective synthesis of (±)-indolizidine 167B,,10.1016/s0040-4039(01)00822-x,2001-07-01,0.6451809123795614
Synlett,Efficient Synthesis of a Key Intermediate of Neurokinin Receptor Antagonists Using a Bifunctional Asymmetric Catalyst,"We report herein an efficient synthetic method for the preparation of 2-[(2R)-arylmorpholin-2-yl]ethanol, a key inter­mediate of neurokinin receptor antagonists. Catalytic asymmetric cyanosilylation of ketone 3 using titanium complex 4 was employed to introduce the required stereochemistry.",10.1055/s-2003-37123,2003-01-01,0.6451797552681277
Organic Process Research & Development,Development of a Scalable Route for a Key Benzothiazole Building Block via a Pd-Catalyzed Migita Coupling with a Nonsmelly Thiol Surrogate,"2-Methylbenzo[ d ]thiazole-6-carbonitrile was internally identified as an important building block and therefore, kg amounts of it needed to be urgently supplied. As the desired benzothiazole was only available in small quantities for a high price (∼1000 USD/g), a robust and scalable route needed to be rapidly developed. The key to success was the use of a 2-iodophenyl N -acetamide precursor to construct the 2-methylbenzo[ d ]thiazole core via a Pd-catalyzed Migita coupling followed by subsequent intramolecular condensation of the intermediate thiophenol onto the N -acetyl group. To avoid the use of malodorous thiols on scale, 2-ethylhexyl 3-mercaptopropionate was used as a nonsmelly, inexpensive thiol surrogate. The Migita coupling was extensively optimized and allowed the reaction to be performed in a dose-controlled manner with regard to the addition of the thiol surrogate at 40 °C, by using only 0.1 mol % Pd 2 dba 3 . The subsequent intramolecular cyclization step was promoted by the one-pot addition of DBU. After aqueous workup and crystallization, 2-methylbenzo[ d ]thiazole-6-carbonitrile was obtained in 81% yield and excellent purity (99.7% a/a) on a 2.0 kg scale.",10.1021/acs.oprd.2c00331,2022-12-06,0.6451719623222425
Journal of Organic Chemistry,"Total Syntheses of Uvarindoles A and B, (±)-Pseudophrynaminol, and (±)-Pseudophrynamines 272A and 270 via Dearomative Indole Alkylation","Herein, we report the first total synthesis of alkaloid uvarindole B with an overall yield of 49% over five steps via double C3-alkylation of 5-bromoindole, Plancher rearrangement, and Negishi coupling as the key steps. We also disclose short total syntheses of uvarindole A, pseudophrynaminol, and pseudophrynamines 272A and 270 via dearomative indole alkylation.",10.1021/acs.joc.5c00062,2025-03-31,0.6451705596830479
Journal of the American Chemical Society,Crotylsilane Reagents in the Synthesis of Complex Polyketide Natural Products:  Total Synthesis of (+)-Discodermolide,"An efficient, highly convergent stereocontrolled synthesis of (+)-discodermolide has been achieved with 2.1% overall yield (27 steps longest linear sequence). The absolute stereochemistry of the C1-C6 (12), C7-C14 (13), and C15-C24 (11) subunits was introduced using asymmetric crotylation methodology. Key elements of the synthesis include the use of hydrozirconation-cross-coupling methodology for the construction of C13-C14 (Z)-olefin, acetate aldol reaction to construct the C6-C7 bond and install the C7 stereocenter with high levels of 1,5-anti stereoinduction, and the use of palladium-mediated sp(2)-sp(3) cross-coupling reaction to join the advanced fragments, which assembled the carbon framework of discodermolide.",10.1021/ja043168j,2005-03-26,0.6451654106480832
Synlett,"A Stereoselective Synthesis of a 3,4,5-Substituted Piperidine of Interest as a Selective Muscarinic (M1) Receptor Agonist","A stereoselective synthesis of (1 RS ,2 SR ,6 SR )-7-benzyl-6-cyclo­butyl-2-methoxymethyl-4,7-diaza-9-oxobicyclo[4.3.0]nonan-8-one, which is representative of a novel series of selective muscarinic (M 1 ) receptor agonists, is described.",10.1055/s-0035-1560753,2015-10-20,0.6451377371614098
Angewandte Chemie International Edition,Construction of Two Vicinal Quaternary Carbons by Asymmetric Allylic Alkylation: Total Synthesis of Hyperolactone C and (−)‐Biyouyanagin A,"Call on triple A: Palladium-catalyzed asymmetric allylic alkylation (Pd-AAA; see scheme) has enabled a concise and efficient synthesis of hyperolactone C and (−)-biyouyanagin A in only six (20 % overall yield) and seven (8 % overall yield) steps, respectively. The enantiomers of these natural products were also prepared by exploiting the same methodology.",10.1002/anie.200902908,2009-09-11,0.645101826624397
Organic Letters,Convergent Synthesis of the Right-Hand Segment of Ciguatoxin,"[reaction: see text] A convergent synthesis of the right-hand half of ciguatoxin (the HIJKLM ring system) has been achieved with complete stereocontrol in the introduction of the stereocenters on the eight-membered I ring. Key steps are Sonogashira coupling, dicobalt complexation, intramolecular conjugate addition, and hydrogenation of an endo-olefin to provide the 39-alpha-methyl group.",10.1021/ol0600741,2006-02-25,0.6450998547432997
Angewandte Chemie International Edition,Total Synthesis of (±)‐Hippolachnin A,The first total synthesis of the marine polyketide (±)-hippolachnin A has been achieved in nine linear steps and an overall yield of 9%. Rapid access to the oxacyclobutapentalene core structure was secured by strategic application of an ene cyclization.,10.1002/anie.201410419,2014-12-04,0.6450992931260832
Journal of Organic Chemistry,Ganglioside GQ1b: Efficient Total Synthesis and the Expansion to Synthetic Derivatives To Elucidate Its Biological Roles,"The convergent total synthesis of ganglioside GQ1b based on the ""cassette approach"" between the nonreducing end GQ1b-core heptasaccharide and glucosylceramide building blocks was accomplished in high overall yield. The use of a sialylalpha(2-->8)sialylalpha(2-->3)galactose sequence as the key building block enhanced the efficiency of the glycan assembly and led to preparative-scale synthesis readily applicable for large-scale preparation. In addition, a judicious choice of p-methoxybenzyl protecting groups on glucosylceramide provided a solution to the previous synthetic problems, including a decrease in the yield of the deprotection steps, and led to elevation of the total yield. Furthermore, unnatural-type GQ1b derivatives were synthesized systematically in good yields by capitalizing on a similar approach in order to elucidate their biological roles.",10.1021/jo8027888,2009-03-18,0.6450932759715183
Synthesis,A New Route to Substituted Pyridines,,10.1055/s-1981-29396,1981-01-01,0.6450896912091078
Tetrahedron,A new route to silyl-substituted cyclobutenones and silylketenes,,10.1016/j.tetlet.2010.10.130,2010-11-01,0.6450896912091078
Tetrahedron,"A new route to 6-substituted 2,3-diaminopyridines",,10.1016/0040-4039(91)80204-j,1991-11-01,0.6450896912091078
Tetrahedron,New route to 2-substituted indoles by pyrolysis of N-acylacetylphenylhydroxylamines,,10.1016/s0040-4039(00)91646-0,1992-03-01,0.6450896912091078
Tetrahedron,"1-Hydrazonyltetrazoles: Fragmentative cyclisation - a new route to substituted 1,2,4-triazoles.",,10.1016/s0040-4039(00)85098-4,1986-01-01,0.6450896912091078
Journal of Organic Chemistry,A New Method for the Synthesis of H<sub>4</sub>-BINOL,"A method amenable to the gram scale synthesis of (R)-H 4-BINOL, a derivative of (R)-BINOL and ligand of interest in asymmetric catalysis, is described. The key step is the net partial hydrogenation of (R)-BINOL made possible by prior bis-etherification of the parent BINOL.",10.1021/jo8004556,2008-05-20,0.6450751997703337
Synthesis,An Efficient Synthesis of Symmetric Bilindiones. Mesobilirubin-Xlllα and Analogs with Varying Alkanoic Acid Chain Lengths,"All articles of this category An inexpensive gram-scale, three-step procedure is described to convert methyl xanthobilirubinate and it alkanoic acid ester analogs (methyl 5-[(3-ethyl-1, 5-dihydro-4-methyl-5-oxo-2 H -pyrrol-2-ylidene)methyl]-1, 4-dimethylpyrrol-3-ethanoate, -propanoate, -butanoate, -pentanoate, -hexanoate) into mesobilirubin-XIIIα and analogs in > 90% yield at each step.",10.1055/s-1992-26102,1992-01-01,0.6450590690026533
Organic Process Research & Development,Kilogram-Scale Synthesis of an Inhaled Corticosteroid,"The development and implementation of a safe and scalable process for the manufacture of corticosteroid PF-4714224 ( 1 ) is described. Initial routes used to synthesise analogues from this series directly from fluocinolone acetonide ( 2 ) were unsuitable for large-scale use. Key aspects of the route are the efficient and simple method for the preparation of the steroid tetraol ( 6 ), acetal formation by reaction of the tetraol with a bisulphite adduct ( 12 ), and isolation of the product by sequential recrystallisations.",10.1021/op200257g,2012-03-14,0.6450311317725895
Journal of Organic Chemistry,"Application of the Helquist Annulation in <i>Lycopodium</i> Alkaloid Synthesis: Unified Total Syntheses of (−)-8-Deoxyserratinine, (+)-Fawcettimine, and (+)-Lycoflexine","A unified strategy for total synthesis of the Lycopodium alkaloids (-)-8-deoxyserratinine (7), (+)-fawcettimine (1), and (+)-lycoflexine (4) is detailed. The key features include a highly efficient Helquist annulation to assemble the cis-fused 6/5 bicycle, facile construction of the aza nine-membered ring system employing double N-alkylation strategy, providing access to the common tricyclic skeleton, asymmetric Shi epoxidation, delivering the desired β-epoxide stereospecifically to furnish (-)-8-deoxyserratinine (7), SmI(2) reduction of dihydroxylation derivative 35 to enable formation of (+)-fawcettimine (1), and a rapid biomimetic transformation of (+)-fawcettimine (1) into (+)-lycoflexine (4) via an intramolecular Mannich cyclization.",10.1021/jo1023188,2011-04-07,0.6450059100314843
Tetrahedron,A highly diastereoselective chloride-mediated dynamic kinetic resolution at phosphorus on-route to a key intermediate in the synthesis of GSK2248761A,,10.1016/j.tetlet.2018.04.018,2018-04-10,0.6449862556868604
Organic Process Research & Development,Improved Process for Azilsartan Medoxomil: A New Angiotensin Receptor Blocker,"An improved process for the active pharmaceutical ingredient of a new angiotensin II AT 1 receptor antagonist, azilsartan medoxomil, has been developed. The results include reinvestigation of the described process as well as its novel modifications. This new process includes transformation of the CN group into amidoxime moiety by aqueous hydroxylamine, its cyclization into the corresponding oxadiazole by treatment with dialkyl carbonates, and the following hydrolysis of the ester and transformation into the medoxomil ester. Several thus far undocumented side products were identified, and some of them were synthesized and duly characterized as potential impurities. Formation and control of possible critical impurities are described.",10.1021/op3002867,2012-12-18,0.6449632973988875
Tetrahedron,"Enantioselective synthesis of GNE-6688, a potent and selective inhibitor of interleukin-2 inducible T-cell kinase (ITK)",,10.1016/j.tetlet.2019.02.014,2019-02-09,0.6449448881837933
Journal of Organic Chemistry,"Regioselective Preparation of 2-Substituted 3,4-Diaryl Pyrroles:  A Concise Total Synthesis of Ningalin B","Methylisocyanoacetate undergoes a 2 + 3 cycloaddition with alpha,beta-unsaturated nitriles to provide a regioselective synthesis of 2-substituted 3,4-diaryl pyrroles. The ease of preparation of alpha,beta-unsaturated nitriles allows the rapid synthesis of pyrroles with varied substituents. Using this method, a key intermediate (1) for the synthesis of the marine natural products lukianol A, lamellarin O, and lamellarin Q was prepared in two steps. A total synthesis of ningalin B (11) was also accomplished utilizing this methodology.",10.1021/jo026445i,2002-12-01,0.6449377687604669
Organic Process Research & Development,Development of an Early-Phase Bulk Enabling Route to Sodium-Dependent Glucose Cotransporter 2 Inhibitor Ertugliflozin,"The development and optimization of a scalable synthesis of sodium-dependent glucose cotransporter 2 inhibitor, ertugliflozin, for the treatment of type-2 diabetes is described. Highlights of the chemistry are a concise, four-step synthesis of a structurally complex API from known intermediate 4 via persilylation–selective monodesilylation, primary alcohol oxidation, aldol-crossed-Cannizzaro reaction, and solid-phase acid-catalyzed bicyclic ketal formation. The final API was isolated as the l -pyroglutamic acid cocrystal.",10.1021/op400289z,2014-01-03,0.6449298066437329
Organic Process Research & Development,"Early Process Development of CH7057288, a Benzofuran-Containing Selective NTRK Inhibitor","This work describes the development of a scalable manufacturing process for CH7057288, a neurotrophic tyrosine receptor kinase (NTRK) inhibitor that selectively targets NTRK positive cancers. NTRK fusions are extremely attractive and promising therapeutic targets, and in order to deliver CH7057288 as a new treatment option for patients, it is crucial to be able to rapidly supply a large amount of this innovative drug for GLP toxicology studies and first-in-human (FIH) studies. By employing an 11-step process, we have been able to synthesize CH7057288 from methyl 2-(3-aminophenyl)-2-methylpropanoate with high purity and in excellent yield. The distinguishing features of this process include sequential double cyclization, leading to four-membered benzofuran-fused heterocycles. By employing this process, we successfully produced a total of 5.5 kg of CH7057288.",10.1021/acs.oprd.3c00434,2024-01-03,0.6448930877269822
Journal of Organic Chemistry,Short Synthesis of the Monoterpene Indole Alkaloid (±)-Arbornamine,"The first total synthesis of the monoterpene indole alkaloid (±)-arbornamine (1) has been completed, which proceeds in only 6 steps and 31% overall yield from three readily available, known compounds. The synthesis features a cascade involving a Pictet-Spengler cyclization/intramolecular ammonolysis to create the tetracyclic core of arbornamine (1) in a single chemical operation. The subsequent elaboration of 5 into 1 was effected by a key reductive Heck reaction and global reduction.",10.1021/acs.joc.8b00529,2018-03-28,0.6448905339106775
Journal of Organic Chemistry,"A General, Catalytic, and Enantioselective Synthesis of (<i>S</i>)-γ-[(<i>S</i>)-1-Aminoalkyl]-γ-lactones","A catalytic asymmetric synthesis of N -phthaloyl ( S )-γ-[( S )-1-aminoalkyl]-γ-lactones, widely used intermediates in the preparation of hydroxyethylene dipeptide isosteres, is described. The highly enantiopure epoxy alcohols arising from the Sharpless epoxidation of ( E )-allyl alcohols are first converted to ( S )- N -phthaloyl-[( S )-1-aminoalkyl]oxiranes by means of an efficient four-step sequence involving the regio- and stereoselective ring opening of the starting epoxide by azide, reduction, phthaloylation, and intramolecular Mitsunobu cyclization of the intermediate phthalimido diol. Treatment of the resulting oxirane with lithium (1 R )-menthyloxyacetylide in the presence of boron trifluoride etherate, followed by in situ hydrolysis of the ynol ether, leads to a (4 R, 5 S )-5-phthalimido-4-hydroxy ester. A Mitsunobu reaction with p -nitrobenzoic acid (which establishes the correct ( S )-configuration at C-4) and subsequent selective saponification of the benzoate and cyclization of the inverted hydroxy ester afford the target N-protected ( S )-γ-[( S )-1-aminoalkyl]-γ-lactones. Using this methodology, lactones 19 and 26 were obtained in seven steps from the readily available epoxy alcohols 5 and 20, respectively, in high enantiomeric purity.",10.1021/jo9720851,1998-05-01,0.6448605721508842
Angewandte Chemie International Edition,Synthetic Studies on Ciguatoxin: A Highly Convergent Synthesis of the GHIJKLM Ring System Based onB-Alkyl Suzuki Coupling,"Access to polycyclic polyethers is facilitated by a synthetic strategy involving two-step B-alkyl Suzuki coupling reactions for the stereoselective construction of the polyether skeleton. Thus, a convergent synthetic route to the heptacyclic GHIJKLM ring system 1 of ciguatoxin, a marine algal toxin implicated in ciguatera fish poisoning, was developed. Bn=benzyl.",10.1002/1521-3773(20010316)40:6<1090::aid-anie10900>3.0.co;2-w,2001-03-16,0.644835116166741
Journal of Organic Chemistry,"Strategy for the Enantioselective Synthesis of <i>trans</i>-2,4-Disubstituted Piperidines:  Application to the CCR3 Antagonist IS811","A strategy for the enantioselective synthesis of trans-2,4-disubstituted piperidines is proposed and applied to the preparation of IS811, a potent CCR3 antagonist. The C2 stereocenter is derived from commercial (R)-epichlorohydrin, while the C4 stereocenter is installed via diastereoselective hydrogenation of an alpha,beta-unsaturated lactone intermediate. Inversion of the original stereocenter via an efficient intramolecular S(N)2 amination affords the piperidine core of IS811. An improved protocol for the lithiation of ethyl propiolate is reported.",10.1021/jo0616963,2006-10-14,0.6448210431726319
Organic Letters,Enantioselective Synthesis of the C(1)–C(11) Fragment of Tedanolide C,A convergent synthesis of the protected C(1)-C(11) fragment 6 of the targeted enantiomer of tedanolide C is described. The key step of the synthesis is the Felkin-Ahn addition of vinyl iodide 7 to aldehyde 8 that proceeds in 80% yield with 4:1 diastereoselectivity.,10.1021/ol303089w,2012-12-18,0.6448027656453531
Journal of Organic Chemistry,Convergent Synthesis of the Quinolone Substructure of BILN 2061 via Carbonylative Sonogashira Coupling/Cyclization,A convergent synthesis of quinolone 2 (key substructure of the protease inhibitor BILN 2061) was developed via palladium-catalyzed carbonylation of 2-iodo-5-methoxyaniline (4) with thiazolylacetylene 5.,10.1021/jo060556q,2006-05-20,0.6447909546260527
Organic Process Research & Development,"The Preparation of Two, Preclinical Amino-quinazolinediones as Antibacterial Agents","This paper describes the synthesis of two amino-quinazolinediones which are potent gyrase/topoisomerase inhibitors and useful as antibacterial agents. The early scale-up work to prepare a chiral side chain on multigram scale and two different amino-quinazolinedione cores is detailed. The enabling synthesis for the side chain employed a previously reported Michael addition of MeNO 2 to an enantiomerically enriched δ-amino-enoate and a two-step de-oxygenation of a lactam. Key synthetic steps for core preparation and completion of the amino-quinazolinediones include dianion-promoted cyclization via intramolecular, nucleophilic aromatic substitution, electrophilic amination, nucleophilic aromatic substitution of the side chain to the core, deprotection and isolation of the hydrochloride salt in acceptable yield.",10.1021/op7000639,2007-05-01,0.6447752247467371
Journal of Organic Chemistry,Ni-Catalyzed C–H Functionalization in the Formation of a Complex Heterocycle: Synthesis of the Potent JAK2 Inhibitor BMS-911543,"BMS-911543 is a complex pyrrolopyridine investigated as a potential treatment for myeloproliferative disorders. The development of a short and efficient synthesis of this molecule is described. During the course of our studies, a Ni-mediated C-N bond formation was invented, which enabled the rapid construction of the highly substituted 2-aminopyridine core. The synthesis of this complex, nitrogen-rich heterocycle was accomplished in only eight steps starting from readily available materials.",10.1021/acs.joc.5b00572,2015-04-07,0.6447724353344855
Tetrahedron,Synthesis of chaetomellic acid A: A potent inhibitor of Ras farnesyl-protein transferase,,10.1016/0040-4039(93)88094-y,1993-10-01,0.6447706553947058
Journal of Organic Chemistry,An Efficient Synthesis of an α<sub>v</sub>β<sub>3</sub> Antagonist,"A practical preparation of an alpha(v)beta(3) antagonist is reported. The antagonist consists of three key components, a tetrahydronaphthyridine moiety, a beta-alanine moiety, and a central imidazolidone moiety. The tetrahydronaphthyridine component was prepared using two different methods, both of which relied on variations of the Friedländer reaction to establish the desired regiochemistry. The beta-alanine component was prepared using Davies' asymmetric 1,4-addition methodology as the key stereo-defining step. The central imidazolidone portion was created from these two components using an effective three-step cyclization protocol. Thus, a highly convergent process for the drug candidate was defined.",10.1021/jo030297u,2004-02-18,0.6447625926018102
Angewandte Chemie International Edition,Divergent Total Syntheses of (−)‐Daphnilongeranin B and (−)‐Daphenylline,"(-)-Daphnilongeranin B and (-)-daphenylline are two hexacyclic Daphniphyllum alkaloids, each containing a complex cagelike backbone. Described herein are the first asymmetric total synthesis of (-)-daphnilongeranin B and a bioinspired synthesis of (-)-daphenylline with an unusual E ring embedded in a cagelike framework. The key features include an intermolecular [3+2] cycloaddition, a late-stage aldol cyclization to install the F ring of daphnilongeranin B, and a bioinspired cationic rearrangement leading to the tetrasubstituted benzene ring of daphenylline.",10.1002/anie.201709762,2017-11-08,0.6447576804115067
Synlett,"Chemoselective Staudinger Strategy in the Practical, Fit for Purpose, Gram-Scale Synthesis of an HCV RNA Polymerase Inhibitor",The use of a late-stage selective Staudinger reaction in the preparation of the novel HCV RNA polymerase inhibitor is described.,10.1055/s-0030-1259085,2010-12-07,0.6447330462017006
Journal of Organic Chemistry,Design and Synthesis of a Structurally Constrained Aminoglycoside,"The synthesis of a constrained tricyclic aminoglycoside derivative is described. This constrained compound fixes the spatial orientation of two critical rings for the minimal motif for binding to biological macromolecules such as RNA and proteins. Methanolysis of neomycin B under acidic conditions produced the bicyclic neamine. Transient protection by the Cu2+ ion and regioselective introduction of protective groups led to intermediate 7, which was used for a key annulation reaction that introduced the tricyclic nucleus into the structural framework. A final hydrogenolysis step to remove the protective groups produced the desired target molecule. The efficient eight-step synthesis was accomplished in 8% overall yield.",10.1021/jo0707636,2007-06-19,0.6447221182507129
Journal of Organic Chemistry,Concise Total Synthesis of (+)-Crocacin C,The cytotoxic natural product (+)-crocacin C ( 1) has been synthesized in 10 linear steps from commercially available Evans' chiral propionimide in 5% overall yield (8 steps from Evans' chiral dipropionate synthon). No protecting groups were utilized.,10.1021/jo800906p,2008-07-16,0.644715783414845
European Journal of Organic Chemistry,"Asymmetric Synthesis of ES‐285, an Anticancer Agent Isolated from Marine Sources","Abstract The asymmetric synthesis of (2 S ,3 R )‐2‐amino‐3‐octanedecanol hydrochloride (ES‐285 · HCl) was achieved in eight steps in ca. 38 % overall yield from the N ‐benzylimine‐derived from ( R )‐2,3‐ O ‐isopropylidene glyceraldehyde, which is easily available on gram scale from the inexpensive precursor D ‐mannitol. Highly diastereoselective addition of methylmagnesium bromide to the N ‐benzylimine was the key step to create the vic ‐amino alcohol moiety with the appropriate configuration. Regioselective ring opening of an intermediate aminoepoxide enabled the introduction of the long hydrocarbon chain at C4.(© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2009)",10.1002/ejoc.200900828,2009-10-21,0.6446802331878353
Journal of Organic Chemistry,Synthesis of HC-Toxin via Matteson Homologation and C–H Functionalization,"A new synthetic route toward host-specific HC-toxin was developed. The HC-toxin belongs to a group of cyclic, tetrapeptide histone deacetylase inhibitors containing the unusual amino acid Aeo. Key steps in the synthesis of this building block include the Matteson homologation to generate the stereogenic centers in the side chain and a C-H functionalization to connect the side chain to a protected alanine.",10.1021/acs.joc.3c00914,2023-07-13,0.644672101035713
Journal of Organic Chemistry,Total Synthesis of (−)-Goniotrionin,"A stereoselective total synthesis of the reported structure of goniotrionin (4) has been accomplished. The key steps involved the opening of a chiral epoxide, a highly diastereoselective Mukaiyama aerobic oxidative cyclization, a selective 1,2-syn Mukaiyama aldol reaction, and a Noyori reduction.",10.1021/jo3004106,2012-03-24,0.6446571829901571
Journal of Organic Chemistry,Practical Asymmetric Approach to Pyrrolidinones:  Efficient Synthesis of (+)-Preussin and (−)-AHPPA,"A novel, dichloroketene−chiral enol ether cycloaddition-based synthesis of enantiopure (+)-preussin and (−)-AHPPA has been realized. The efficient, highly stereoselective approach, which involves a Beckmann ring expansion reaction to access the key pyrrolidinone, proceeds in ca. 16% overall yield for each of the compounds.",10.1021/jo9801162,1998-06-11,0.6446486105360951
Journal of Organic Chemistry,"Enantiospecific Total Synthesis of (−)-Polyoxamic Acid Using 2,3-Aziridino-γ-lactone Methodology","The non-natural enantiomer of polyoxamic acid was synthesized in six steps from 2,3-aziridino-gamma-lactone 7 with an overall yield of 10%. The key step of the strategy is a deprotection-protection sequence on the nitrogen atom of the aziridine ring required for aziridine activation toward nucleophilic ring opening.",10.1021/jo035039b,2003-11-01,0.6446362804856742
Organic Letters,An Efficient Enantioselective Synthesis of (<i>S</i>)-(−)-Acromelobic Acid,"[reaction: see text] A highly efficient enantioselective synthesis of (S)-(-)-acromelobic acid (1) was achieved via asymmetric hydrogenation of dehydroamino acid derivative (3) using (R,R)-[Rh(DIPAMP)(COD)]BF(4) catalyst followed by removal of protective groups in >98% ee and good over all yield. The key intermediate (3) was prepared from the commercially available citrazinic acid (4) in six steps.",10.1021/ol006363l,2000-10-05,0.6446342869904376
Synlett,Biomimetic Total Synthesis of Scabellone B,"A biomimetic total synthesis of scabellone B is described. Through sequential regioselective introduction of a geranyl group by means of silyl protection, oxidative dimerization, and biomimetic oxo-6π electrocyclization with good cyclization selectivity, a biomimetic ­approach to scabellone B was achieved in five steps and 32% overall yield.",10.1055/s-0037-1610178,2018-06-18,0.6446250776720643
Organic Process Research & Development,Initial Route Scouting and Final Process Development for the Multi-Kg Production of 3-Fluoro-6-methoxyquinoline from <i>p</i>-Anisidine and 2-Fluoromalonic Acid,"A scalable route to 3-fluoro-6-methoxyquinoline needed to be developed as multi-kg amounts of this heterocycle were required. Initial route development focused on the formation of the key C–F bond via a Balz–Schiemann reaction or electrophilic fluorination using Selectfluor. Both routes were developed on laboratory scale and provided gram amounts of 3-fluoro-6-methoxyquinoline. However, due to process safety concerns and high step counts, both routes were not suitable for further scale up. Therefore, a third approach was developed, in which the desired heterocycle was formed via condensation of p -anisidine with 2-fluoromalonic acid, two inexpensive and commercially available starting materials. After intensive optimization and safety studies, this POCl 3 -mediated process was successfully scaled up to a 32 kg scale. After final hydrodechlorination, 12 kg of 3-fluoro-6-methoxyquinoline with excellent purity was produced.",10.1021/acs.oprd.1c00414,2022-01-20,0.644611491101445
Organic Letters,Total Synthesis of (+)-Decursivine,The first asymmetric synthesis of natural indole alkaloid (+)-decursivine was accomplished. The key step involves the PIFA-mediated intramolecular [3 + 2] cycloaddition of 5-hydroxytryptophan with a substituted cinnamamide in a highly diastereoselective manner.,10.1021/ol2021669,2011-09-14,0.6446031371452847
Organic Letters,Synthetic Studies on Maitotoxin. 2. Stereoselective Synthesis of the WXYZA′-Ring System,"The stereoselective synthesis of the WXYZA'-ring system of maitotoxin has been accomplished via a linear synthetic approach, in which key reactions were SmI 2-induced cyclization of beta-alkoxyacrylate for the construction of the A'-, Y-, and X-rings and 6- endo cyclization of hydroxy vinylepoxide for that of the Z- and W-rings.",10.1021/ol800268c,2008-04-08,0.6445873820353895
Synthesis,"An Efficient Directed Claisen Reaction Allows for Rapid Construction of 5,6-Disubstituted 1,3-Dioxin-4-ones","An efficient directed Claisen reaction between tert -butyl propionate and phenyl propionate is described. This enables a practical synthesis of 6-ethyl-2,2,5-trimethyl- 4H -1,3-dioxin-4-one and thereby ( Z )-[(4-ethylidene-2,2,5-trimethyl-4 H -1,3-dioxin-6-yl)oxy]trimethylsilane, a key building block in our synthesis of macrolide antibiotics. The three-step route elaborated for the preparation of the latter substance requires no chromatography and is amenable to large-scale synthesis.",10.1055/s-0034-1378822,2015-08-03,0.6445667929871066
Synthesis,Assembly of the Nosiheptide A-Ring: A Fruitful Lesson,"The synthesis of a 28-membered thiopeptide macrocycle is described. Key steps are mild aza-Wittig thiazole ring closures, a scandium(III)-mediated regioselective ester hydrolysis, and a highly efficient macrolactam formation with its 3-hydroxypyridine nucleus orthogonally protected.",10.1055/s-0032-1317810,2013-04-25,0.6445606657606012
Synlett,Synthesis of Two Key Intermediates for Hennoxazole A,"All articles of this category Two key intermediates used for the synthesis of hennoxazole A have been synthesized. The anti -β-protected hydroxyl epoxide 5 was prepared from (R)-(+)-malic acid by the stereoselective alkylation utilizing a chiral borane reagent as a key step. Construction of the dithiane substituted oxazole 6 was achieved by the coupling of L-(+)-lactic acid and L-serine methyl ester hydrochloride with diethyl phosphorocyanidate, followed by the construction of the oxazole ring. stereoselective synthesis - hennoxazole A - anti -β-protected hydroxyl epoxide - dithiane substituted oxazole",10.1055/s-1997-17829,2004-03-22,0.6445520624099572
Tetrahedron,"A synthetic approach for (S)-(3-benzyl-3-methyl-2,3-dihydro-benzofuran-6-yl)-piperidin-1-yl-methanone, a selective CB2 receptor agonist",,10.1016/j.tetlet.2012.04.076,2012-04-24,0.6445308210746786
Organic Letters,Total Synthesis of (−)-Nakadomarin A,"A concise diastereoselective total synthesis of (-)-nakadomarin A has been completed in 21 steps from D-pyroglutamic acid. Key steps include an enecarbamate Michael addition/furan-N-acyliminium ion cascade cyclization to provide the tetracyclic core and ring-closing alkyne and alkene metatheses to construct the fifteen- and eight-membered azacycles, respectively.",10.1021/ol102079z,2010-10-08,0.6445243917501647
Journal of Organic Chemistry,Scalable Asymmetric Synthesis of the All <i>Cis</i> Triamino Cyclohexane Core of BMS-813160,"triamino cyclohexane core. Medicinal and process chemistry groups at BMS have previously published synthesis strategies for chemotypes similar to the target molecule, but a streamlined approach amenable for longer-term supply was necessary. A new synthetic route was conceptualized, experimentally investigated, and determined to meet the criteria for efficiency that addressed key limitations of previous approaches. Adopting/optimizing the Trost asymmetric allylic amination desymmetrization methodology was a key tool used to produce a synthesis intermediate with high optical purity. In addition, developing a tandem Mannich-aza-Michael reaction to obviate the need for a Curtis/acylation sequence and a novel reductive amination/thermal lactamization to circumvent Freidinger-type pyrrolidone preparation are some of the synthesis improvements that enabled access to the target molecule to fulfill long-term supply requirements.",10.1021/acs.joc.1c01162,2021-08-06,0.6445159920268985
Journal of the American Chemical Society,Total Synthesis of (±)-Garsubellin A,"The first total synthesis of garsubellin A, a neurotrophic compound with potent choline acetyltransferase-inducing activity, is described. Keys for success were (1) stereoselective intermolecular aldol reaction at the C-4 position with acetaldehyde, (2) stereoelective Claisen rearrangement to introduce an allyl group to the most sterically crowded position at C-6, (3) ring-closing metathesis to construct the B-ring, and (4) Wacker-type oxidative C-ring formation. This synthetic route can be extended to an asymmetric synthesis of garsubellin A using the Koga catalytic enantioselective alkylation, which produced enantioenriched alpha-prenyl cyclohexenone with excellent enantioselectivity (95% ee).",10.1021/ja055301t,2005-09-21,0.6445104312478351
Journal of Organic Chemistry,Exploiting Alkylquinone Tautomerization for the Total Synthesis of Calothrixin A and B,"The pentacyclic alkaloid calothrixin B (1) has been synthesized in 5 steps from murrayaquinone A (9). The key step involved the union of boryl aniline 31 with brominated murrayaquinone A (26). In this transformation, alkylquinone 26 undergoes tautomerization to a quinone methide, which is intercepted by boryl aniline 31 to forge a new C-N bond. An intramolecular Suzuki coupling, followed by dehydrogenative aromatization, completed the synthesis of calothrixin B. Subsequent N-oxidation of calothrixin B delivered calothrixin A. The successful synthesis of these alkaloids and the challenges that led to the development of the final synthesis plan are reported herein.",10.1021/acs.joc.7b02101,2017-10-31,0.6445026125302524
Synthesis,Total Synthesis of Bis-anthraquinone Antibiotic BE-43472B,"This is a full account of our synthetic endeavor on the total synthesis of bis-anthraquinone antibiotic BE-43472B, an unusual octacyclic aromatic polyketide with a bis-anthraquinone scaffold. Three key steps enabled a facile access to the anthraquinone unit corresponding to the ABCF rings; (1) cyclo-condensation or -addition of benzonitrile oxides with cyclic enone derivatives, (2) benzoin cyclization for the stereoselective ring fusion with an angular hydroxy group, and (3) pinacol rearrangement for stereoselective installation of the angular aryl group. Other keys for the success include, (4) diastereoselective methylation of a lactol derivative, and (5) late-stage installation of the C3 hydroxy group through stereoselective oxirane ring formation via halohydrin derivatives. Whereas oxidation of the double bond in the enone with an adjacent 1,3-diketone moiety failed, the projected oxidation was achieved with the alkene keeping the isoxazole moiety intact as a 1,3-diketone equivalent. In the racemic total synthesis, X-ray crystal structure analysis of the target was achieved, proving the three-dimensional architecture for the first time. The asymmetric total synthesis was also achieved by exploiting a cycloadduct of the nitrile oxide and the enantiomerically pure cyclohexenone, which was convertible to the common intermediate via dehydrogenation followed by alkoxycarbonylation.",10.1055/s-0037-1610136,2018-05-15,0.644491966685675
Journal of the American Chemical Society,Enantioselective Synthesis of Azamerone,"A concise and selective synthesis of the dichlorinated meroterpenoid azamerone is described. The paucity of tactics for the synthesis of natural-product-relevant chiral organochlorides motivated the development of unique strategies for accessing these motifs in enantioenriched forms. The route features a novel enantioselective chloroetherification reaction, a Pd-catalyzed cross-coupling between a quinone diazide and a boronic hemiester, and a late-stage tetrazine [4+2]-cycloaddition/oxidation cascade.",10.1021/jacs.8b12566,2019-02-01,0.6444427820198486
Tetrahedron,"A one step synthesis of 1,4-benzodiazepines: synthetic studies on neothramycin",,10.1016/s0040-4039(00)98268-6,1985-01-01,0.6444421604201177
Tetrahedron,Total synthesis of the marine sponge pigment fascaplysin,"Fascaplysin (1), an antimicrobial and cytotoxic red pigment from the marine sponge Fascaplysinopsis sp., has been synthesized in seven steps from indole (65% yield). The pivotal intermediate in the synthesis is diindole 3 which is induced to undergo acid-catalyzed cyclization and dehydrogenation to afford the desired pentacycle 2 in > 90% yield. Peracid oxidation of 2 yields fascaplysin.",10.1016/s0040-4039(00)97367-2,1990-01-01,0.6444218178646093
Synlett,"Stereoselective Synthesis of (3R,5R)-cis-3-Hydroxy-5-phenylpyrrolidine","All articles of this category Cis -3-hydroxy-5-phenyl pyrrolidine could be synthesized stereoselectively from inexpensive starting materials, ( R )-(+)-ethyl-4-chloro-3-hydroxybutanoate and ( R )-(+)-4-chloro-3-hydroxybutyronitrile. Key feature involves face- and chemo-selective hydrogenation of cyclic imine 5 as the common key intermediate using Pt/C catalyst. Transformations described here will allow a practical synthesis of novel carbapenems, 1 and 2 . reductive amination - cyclic imine - hydrogenation - pyrrolidine - 1 β -methylcarbapenem",10.1055/s-2001-18106,2001-01-01,0.6444206939833239
Organic Process Research & Development,"Practical Large-Scale Synthesis of Cefmatilen, A New Cephalosporin Antibiotic","A practical large-scale process for the synthesis of cefmatilen hydrochloride hydrate ( 1 ), a new oral cephalosporin antibiotic, is described. Several impurities are isolated from a bulk drug and identified. Side reactions are discussed in order to prevent them. The conditions were optimized to control the formation of impurities. The process is amenable to a multikilogram-scale preparation. Several kilograms of compound 1 for clinical trials were successfully prepared by this process from the three starting materials (7-aminocephem hydrochloride 4, triethylammonium acetate 5, and triazole 7 ) on a pilot scale in overall yields of 61−65% (10−14% higher than those for the previous process).",10.1021/op049920i,2004-07-16,0.6443966826179444
Organic Letters,The Total Synthesis of Hyperfirin via a Cyclooctadiene Strategy,"Polycyclic polyprenylated acylphloroglucinols (PPAPs) combine compelling structural complexity with effective biological activity. The total synthesis of Hyperfirin is reported as one linear sequence. Key to this novel modular strategy is to access the bicyclo[3.3.1]nonane-2,4,9-trione framework via transannular acylation of a decorated eight-membered ring, followed by late stage bridgehead substitution. The described route adds flexibility to PPAP construction and broadens the scope of eight-membered ring chemistry.",10.1021/acs.orglett.4c01836,2024-07-12,0.6443875226220738
Synlett,"Iminophosphorane-Based Preparation of 2,5-Disubstituted Oxazole Derivatives: Synthesis of the Marine Alkaloid Almazole C","A four-steps synthesis (32% overall yield) of marine alkaloid almazole C isolated from the red seaweed Haraldiophylum sp. is described. The key step, construction of the central 2,5-disubstituted oxazole ring is based on the aza-Wittig reaction of the iminophosphorane derived from the α-azidoacetyl indole and (S)-N-phthaloylphenylalanyl chloride.",10.1055/s-2007-967995,2007-02-01,0.6443850266037374
Organic Process Research & Development,Development of a Practical High-Yield Industrial Synthesis of Pergolide Mesylate,"The development of a high-yield and low environmental impact synthesis able to deliver highly pure pergolide mesylate 1 is described. The process [seven chemical steps (four telescoped), three steps of isolation of intermediate, and only one drying] affords pergolide mesylate 1 in 75−81% overall yield from dihydrolysergic acid 4 with >99.8% purity.",10.1021/op0501747,2006-02-02,0.6443841012470218
Organic Letters,Total Synthesis and Structure Revision of Boholamide A,"The 15-membered cyclic depsipeptide boholamide A and an epimer were prepared by total synthesis for the first time, thus leading to a revision of C6 stereochemistry in the originally proposed structure of natural boholamide A. This convergent route features achievement of a macro-lactamization step in a gram scale. The revised boholamide A was sythesized with 16 linear steps in 5.46% overall yield. This work facilitates the investigations of boholamide A as a potential hypoxia-selective anticancer agent.",10.1021/acs.orglett.1c01382,2021-06-10,0.6443828886963854
Organic Letters,Total Synthesis of Pteridic Acid A,"A convergent approach to the total synthesis of pteridic acid A, having potent plant growth regulator activity, is described. Key steps include the desymmetrization of bicyclic olefin with Brown's chiral hydroboration, acid-mediated spiroketalization, and zirconium-catalyzed ethylmagnesation protocol to install the ethyl stereocenter at C14.",10.1021/ol9026842,2009-12-18,0.6443557525371869
Journal of Organic Chemistry,"An Efficient Fischer Indole Synthesis of Avitriptan, a Potent 5-HT<sub>1D</sub> Receptor Agonist","An efficient synthesis of the antimigraine drug candidate avitriptan ( 1, BMS 180048) is reported. The key step is a two-phase Fischer indolization reaction between hydrazine 6 and 5-chlorovaleraldehyde, 20, to give the chloropropylindole 35, which is susceptible to acid-catalyzed degradation under the reaction conditions required for its formation. Sequential coupling of 35 with piperazine, 26, and 4-chloro-5-methoxypyrimidine, 24, gives the title compound in 40−45% overall yield. Significant improvements in the syntheses of the known starting materials, hydrazine 6, 5-chlorovaleraldehyde, 20, and 4-chloro-5-methoxypyrimidine, 24, were also achieved.",10.1021/jo971368q,1997-12-01,0.6443452890243808
Tetrahedron,A new synthesis of the GPIIb/IIIa receptor antagonist SB-214857-A,,10.1016/s0040-4039(01)00843-7,2001-07-01,0.6443373625504148
Synlett,Stereoselective Total Synthesis of (+)-Sapinofuranone B,"A stereoselective total synthesis of sapinofuranone B is described starting from commercially available l-(+)-diethyl tartrate using a ring-opening reaction, a Mitsunobu inversion, and a Sonogashira coupling as the key steps.",10.1055/s-0030-1258583,2010-09-23,0.6443370222920893
Tetrahedron,An eight steps synthesis of an orally active antihypertensive carba-prostacyclin analog,,10.1016/s0040-4039(00)94119-4,1983-01-01,0.6443131693001937
Organic Process Research & Development,Development of a Manufacturing Process for 1-(1-Pyridin-2-yl methyl-piperidin-4-yl)-1<i>H</i>-indole:  A Key Intermediate for Protein Kinase C Inhibitor LY317615,"This contribution describes process development leading to the production of 1-(1-pyridin-2-yl methyl-piperidin-4-yl)-1 H -indole ( 11 ). The title compound 11 was produced via a Leimgruber−Batcho indole synthesis using key intermediates 2-(2,2-dimethoxyethyl)benzenamine ( 6 ) and, 1-(2-pyridinylmethyl)-4-piperidinone camphor sulfonate ( 9 ). Direct crystallization of 11 from IPA or ethanol−water was developed to provide ( 11 ) with <1% impurities and high yield (78%). The combined process leads to a five-step synthesis of 11 that was efficient and reflected Eli Lilly and Company's commitment to implementation of environmental friendly processes whenever feasible.",10.1021/op060068k,2006-10-24,0.6443018876328471
Journal of Organic Chemistry,An Efficient and Highly Stereocontrolled Route to Bulgecinine Hydrochloride,"(-)-Bulgecinine is a nonproteinogenic amino acid component present in bulgecins A, B, and C, antibiotic glycopeptides derived from Pseudomonas acidophila and Pseudomonas mesoacidophila. In combination with beta-lactam antibiotics, bulgecins exihibit a unique synergistic antibacterial activity against various Gram-negative microorganisms. Utilizing d-serine as a chiral template and employing a highly regio- and stereoselective intramolecular amidomercuration-oxidation protocol in the key pyrrolidine ring forming step, an efficient total synthetic route to enantiopure bulgecinine is reported herein.",10.1021/jo035441q,2003-12-19,0.6443006074825818
Synthesis,"An Improved Synthesis of Methyl 1,3-Dihydro-2<i>H</i>-pyrrolo[3,4-<i>b</i>]quinoline-2-carboxylate","Optimization of an old route leads very easily, in four steps, to methyl 1,3-dihydro-2H-pyrrolo[3,4-b]quinoline-2-carboxylate in 45% yield from commercial starting materials. This procedure can be compared to recently described methods whose yields were only 23-28% and required five to seven steps from advanced intermediates and chromatographic purifications. Moreover, using this method, the title compound can now be obtained in large quantities.",10.1055/s-2007-990821,2007-10-25,0.6442988551056082
Organic Process Research & Development,Efficient and Scalable Synthesis of Glucokinase Activator with a Chiral Thiophenyl-Pyrrolidine Scaffold,Herein we describe the practical synthesis of a potent glucokinase activator ( 1 ) that has a chiral thiophenyl-pyrrolidine scaffold. The key to the successful synthesis was the application of a telescoped chiral-pool synthesis from a commercially available l -proline methyl ester derivative to introduce the chirality of the thiophenyl-pyrrolidine moiety. This second-generation synthesis of 1 provided several advantages over the previous method including an operational simplicity and avoidance of purification by column chromatography. The industrial relevance of this synthetic method in large-scale preparation was demonstrated by the production of 54.6 kg of 1 with an excellent chemical and optical purity.,10.1021/acs.oprd.8b00354,2018-12-11,0.6442630439523882
Journal of the American Chemical Society,"An Efficient, Stereocontrolled Synthesis of a Potent Omuralide−Salinosporin Hybrid for Selective Proteasome Inhibition","A short and highly stereocontrolled synthesis of the potent proteasome inhibitor 3 from the (S)-threonine-derived oxazoline 4 has been developed. The synthetic sequence is summarized in Scheme 1. Aldol coupling of the zinc enolate of 4 with isobutyraldehyde and subsequent silylation provided the TBS ether 5 diastereoselectively (10:1). Reductive cleavage of the oxazoline ring of 5 followed by Swern oxidation of the resulting amino alcohol afforded amino ketone 6, converted further by N-acylation to the acrylamide 7, whose structure was confirmed by X-ray crystallographic analysis. Acrylamide 7 was cyclized to 8 by a novel application of the Kulinkovich Ti(II)-cyclopentene complex. Silylation of 8 to 9 and radical cyclization at low temperature produced the bicyclic lactam 10 with complete control of all stereocenters. Hydroxy desilylation and N-deprotection of 10 gave the dihydroxy ester 11, which was converted to 3 by a novel three-step sequence: (1) demethylation with [Me2AlTeMe]2, (2) combined beta-lactonization and chlorination, and (3) desilylation to effect cleavage of the TBS ether.",10.1021/ja052376o,2005-06-01,0.6442514394995558
Journal of Organic Chemistry,Specific C−C Bond Construction by Remote C−H Activation:  Synthesis of (−)-<i>trans</i>-Cembranolide,"The first total synthesis of (−)- trans -cembranolide ( 1 ), isolated from Sinularia mayi Luttschw., is described. The key step in the synthesis is the diastereoselective Rh-mediated cyclization of the enantiomerically pure diazo ester 4 to the tetrahydrofuran 3a .",10.1021/jo971065w,1997-09-01,0.6442390663133376
Tetrahedron,An efficient total synthesis of (±)-methyl jasmonate,,10.1016/s0040-4039(01)92344-5,1981-01-01,0.6442354986910678
Tetrahedron,Total synthesis of queen substance of honeybee using an organosilicon route,,10.1016/0040-4039(91)80490-w,1991-12-01,0.6442322471971054
European Journal of Organic Chemistry,Synthesis of the C‐8–C‐24 Fragment of Maltepolide C by Using a Tandem Dihydroxylation/S<sub>N</sub>2 Cyclization Sequence,"Abstract A highly stereoselective synthesis of the C‐8–C‐24 fragment of maltepolide C has been achieved in a convergent and efficient manner by utilizing a tandem Sharpless asymmetric dihydroxylation (SAD)/S N 2 cyclization reaction sequence as the key step. Other important steps include a Crimmins‐modified Evans aldol reaction, a Brown asymmetric allylation, a Horner–Wadsworth–Emmons olefination, and a Corey–Bakshi–Shibata (CBS) reduction.",10.1002/ejoc.201500629,2015-07-02,0.6442201078740948
Tetrahedron,"A stereospecific synthesis of both enantiomers of 2-(1′-amino-2′-methylpropyl) imidazole, a key synthon in the synthesis of SB 203386; a potent protease inhibitor",,10.1016/s0040-4039(97)00070-1,1997-02-01,0.6442182208753795
Tetrahedron,High-yield synthesis of pyrrolidinyl PNA monomers,,10.1016/j.tetlet.2011.08.167,2011-09-11,0.6442099790849529
Synthesis,A High-yield Synthesis of<i>dl</i>-Mevalonolactone,,10.1055/s-1974-23416,1974-01-01,0.6442099790849529
Journal of Organic Chemistry,Synthesis and Fucosidase Inhibitory Study of Unnatural Pyrrolidine Alkaloid 4-<i>epi</i>-(+)-Codonopsinine,"The total synthesis of enantiopure 4-epi-(+)-codonopsinine was achieved in 10 steps starting from D-ribose as a chiral building block. The key step involved a highly stereoselective nucleophilic addition of a Grignard reagent to a protected ribosylamine. Synthesis of the N-desmethyl derivative and its p-tolyl analogue was also accomplished, and the compounds were assayed against α-fucosidase.",10.1021/jo200176u,2011-04-15,0.6441995633113039
Green Chemistry,A scalable and eco-friendly total synthesis of poly(ADP-ribose) polymerase inhibitor Olaparib,A scalable and eco-friendly total synthesis of PARP inhibitor.,10.1039/d3gc02617e,2023-01-01,0.6441785773388974
Tetrahedron,A simple synthesis of 2h-pyrans; A one-step synthesis of flindersine,,10.1016/s0040-4039(00)91410-2,1975-01-01,0.644172437423051
Organic Process Research & Development,"Process Development for the First GMP Synthesis of SGD-9501-TFA, Part 1: Synthesis of Two Oligopeptide Fragments","The discovery of novel auristatin-derived antibody drug conjugates (ADCs) with attenuated bystander activity is an area of intense research. Recently, drug-linker SGD-9501 emerged as a promising clinical candidate possessing favorable off-target toxicity. To support the clinical supply of ADCs based on this drug-linker, we set out to develop a first-in-human (FIH) amenable GMP manufacturing route. This report describes the process development of two oligopeptide fragments covering four synthetic steps in the seven-step convergent solution phase synthesis of SGD-9501 from commercial reagents. The highlights within this report include the discovery and development of three crystallizations, the use of PAT to control impurities formed in a direct coupling of N, N -dimethyl- O -unprotected serine, and the development of mild acid promoted boc and tert -butyl ester deprotection conditions that optimized impurity control and subsequent isolation. Each step was performed on a >500 g scale for the GMP campaign and achieved a >75% yield and >98% LC area percent (LCAP) purity.",10.1021/acs.oprd.4c00317,2024-09-16,0.6441652334979296
Journal of the American Chemical Society,Total Synthesis of (−)-<i>N</i>-Methylwelwitindolinone B Isothiocyanate via a Chlorinative Oxabicycle Ring-Opening Strategy,"The first total synthesis of N-methylwelwitindolinone B isothiocyanate is reported. The route features several key steps, including a regio- and diastereoselective chlorinative oxabicycle ring-opening reaction to introduce the challenging alkyl chloride motif.",10.1021/ja5087672,2014-10-02,0.6441574427172613
Organic Process Research & Development,Development of a Pilot-Plant Process for a Nevirapine Analogue HIV NNRT Inhibitor,"The pilot-plant synthesis of nevirapine analogue 1 is described. The compound was prepared in eight steps from substituted pyridine raw materials and 4-hydroxyquinoline. The key transformation involves a novel one-pot conversion of an arylhalide to arylacetic acid under palladium catalysis, followed by regioselective reduction via in situ generated BH 3 /THF to the arylethanol intermediate 2 . All stages were carried out on 10−150-kg scale.",10.1021/op8000756,2008-06-28,0.6441573556216346
Tetrahedron,"Total synthesis of haliclamine A, a macrocyclic marine alkaloid related to the key biogenetic intermediate of manzamines",,10.1016/s0040-4039(97)10368-9,1997-12-01,0.6441550680936671
Organic Letters,Asymmetric Total Synthesis and Stereochemical Elucidation of the Antitumor Agent PM-94128,"[reaction: see text]. PM-94128, a novel depsipeptide antitumor agent, has been synthesized for the first time through a highly stereocontrolled route. The key steps for the synthesis of the dihydroxyamino acid moiety involve a diastereoselective addition of tert-butyl lithiopropiolate to a chiral nitrone and a 2,3-dihydro[1,2]oxazin-6-one dihydroxylation. The synthesis serves to define the relative as well as the absolute configuration of the natural product (bearing five stereogenic centers).",10.1021/ol035470n,2003-10-01,0.644145476248149
Synthesis,"Total Synthesis of Chatenaytrienins-1, -3 and -4 and Muridienins-1–4 Enabled by C(sp)–C(sp3) Sonogashira Coupling","Abstract Concise and efficient protecting-group-free total syntheses of chatenaytrienins-1, -3, -4 and muridienins-1–4 have been achieved. The key steps involve ring-closing metathesis (RCM) and C(sp)–C(sp3)-Sonogashira coupling. This work reports the first total syntheses of chatenaytrienin-3 and muridienins-1–4 in seven linear steps and high overall yields.",10.1055/a-1828-5837,2022-04-19,0.6441277718507749
Organic Letters,"The First Total Synthesis of (±)-Arisugacin A, a Potent, Orally Bioavailable Inhibitor of Acetylcholinesterase","The first convergent total synthesis of (+/-)-arisugacin A was accomplished by stereoselective construction of the arisugacin skeleton via a Knoevenagel-type reaction of an alpha,beta-unsaturated aldehyde with a 4-hydroxy 2-pyrone and stereoselective dihydroxylation followed by deoxygenation.",10.1021/ol017046x,2002-01-08,0.6441199086797907
Tetrahedron,"A synthetic route to 1,2,4,5-tetrahydro-3H-benz[e]indoles",,10.1016/s0040-4039(01)88263-0,1969-01-01,0.6441136753359669
Journal of the American Chemical Society,Enantioselective Total Synthesis of (+)-Hinckdentine A via a Catalytic Dearomatization Approach,"Optically pure hinckdentine A was synthesized on a 300 mg scale via an asymmetric catalysis-based strategy. The key steps to the first asymmetric synthesis involved (i) enantioselective dearomative cyclization of an achiral N-acyl indole that allowed for the efficient construction of the key polycyclic indoline intermediate with a crucial tetrasubstituted stereogenic carbon center, (ii) Beckmann fragmentation-mediated ring expansion, (iii) rearrangement-based introduction of an anilinic nitrogen atom, (iv) regioselective tribromination, and (v) final closure of the cyclic amidine moiety.",10.1021/jacs.6b10237,2016-10-22,0.6441051212622716
Organic Letters,Total Synthesis of the Reported Structure of Stresgenin B Enabled by the Diastereoselective Cyanation of an Oxocarbenium,"We report the first total synthesis of the reported structure of the heat shock protein expression inhibitor stresgenin B. The synthesis features (1) diastereoselective cyanation of an oxocarbenium intermediate en route to the synthetically challenging α-amido dioxolane, (2) Pd-catalyzed hydration of an unstable nitrile, and (3) late-stage Au-catalyzed Meyer-Schuster rearrangement or Ce-mediated Peterson olefination to furnish the exocyclic α,β-unsaturated ester. Our synthetic endeavors allowed us to conclude that the structure of stresgenin B requires revision.",10.1021/acs.orglett.8b03219,2018-12-07,0.6440957995419966
Organic Letters,"Stereocontrolled Synthesis of 2-Substituted-1,3-Azasilaheterocycles","Chiral alpha-silylsulfinamides, prepared by the treatment of an alkyldiphenylsilane with lithium followed by its addition to a sulfinimine, can be applied to the synthesis of 1,3-azasilaheterocycles as derivatives of cyclic alkaloids. This synthetic route, which involves intramolecular substitution of an amino alcohol or cyclization of an amino acid promoted by 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), represents a convenient means for accessing these silicon-containing heterocycles.",10.1021/ol101379t,2010-07-12,0.6440845184879984
Tetrahedron,"Stereoselective reduction of unsaturated 1,4-diketones. A practical route to chiral 1,4-diols",,10.1016/s0040-4039(96)02476-8,1997-02-01,0.6440791190341001
Synlett,First Synthesis of Marine Alkaloid(±)-Bengacarboline,"Bengacarboline 1, a marine alkaloid, potent inhibitor of topoisomerase II, has been synthesized in nine steps from indol-3-carboxylic acid and tryptamine.",10.1055/s-2003-40836,2003-01-01,0.6440449765301709
Journal of the American Chemical Society,"Short, Enantioselective Total Synthesis of Okaramine N","The first enantioselective total synthesis of a member of the okaramine family of bis-indole alkaloids, okaramine N (1), has been accomplished via intermediates 2-7, as outlined. The N-prenylated derivative of (S)-tryptophan methyl ester (2) was coupled with Fmoc-protected N-tert-prenylated tryptophan (3) to form the amide 4 in 70% yield. Pd(II)-mediated cyclization/rearrangement, a key step in the synthesis, transformed 4 into the indoloazacine 5 (44%), which was deprotected and cyclized in a single step to give the hexacyclic diketopiperazine 6 (95%). In the following novel and key sequence, 6 was transformed into 1: (1) selective ene reaction with N-methyltriazolinedione, (2) photooxidation of the remaining tert-prenylated indole subunit to provide 7, and (3) thermal retroene reaction of 7 to afford okaramine N (70% from 6).",10.1021/ja034491+,2003-04-18,0.6440440047741348
Tetrahedron,"A new and convergent synthesis for 2,5-diamino-tetrahydropyrimidones",,10.1016/s0040-4039(03)00226-0,2003-03-01,0.6440219802627516
Organic Letters,"Total Synthesis and Structure Confirmation of (−)-Asimitrin, a C<sub>37</sub> Annonaceous Acetogenin with a Hydroxylated Adjacent Bis-Tetrahydrofuran Core","The total synthesis and structure confirmation of the potent cytotoxic agent (−)-asimitrin ( 1 ), a C 37 annonaceous acetogenin having a hydroxylated adjacent bis-tetrahydrofuran (THF) core, are described. The present synthesis features a highly stereoselective, chelate-controlled intramolecular amide enolate alkylation (IAEA) for the synthesis of key intermediate 17-hydroxy-16,17- erythro -16,19- trans -THF 6, our direct ketone synthesis/ l -Selectride reduction protocol for stereoselective introduction of the C(21)–C(34) unit, Sharpless asymmetric dihydroxylation (SAD), and internal Williamson etherification for construction of the 20,23- trans -THF ring.",10.1021/acs.orglett.3c02495,2023-08-31,0.6440151702312418
Synthesis,Synthetic Studies towards Optically Active 13-Oxyingenol via Asymmetric Cyclopropanation,"The enantioselective synthesis of a seven-membered enone compound, the key intermediate of our previous synthesis of the inside-outside framework of 13-oxyingenol in racemic form, was achieved by using asymmetric cyclopropanation and reductive deoxygenation as key steps.",10.1055/s-0030-1259430,2011-01-31,0.6440091223161029
Journal of Organic Chemistry,Progress toward the Total Synthesis of Lucentamycin A: Total Synthesis and Biological Evaluation of 8-<i>epi</i>-Lucentamycin A,Synthetic efforts toward the cytotoxic peptides lucentamycins A-D are described that resulted in the total synthesis and biological evaluation of 8-epi-lucentamycin A in 15 steps with 2.2% overall yield. The key epi-nonproteogenic 3-methyl-4-ethylideneproline was synthesized via a titanium-mediated cycloisomerization reaction.,10.1021/jo902115s,2009-10-29,0.644004535009282
Tetrahedron,Synthetic key intermediates of glycocinnamoylspermidines ; diaminohexosyloxycinnamate and aminopentose disaccharide moieties,,10.1016/s0040-4039(00)87195-6,1982-01-01,0.6440034803078833
Journal of the American Chemical Society,Applications of Zr-Catalyzed Carbomagnesation and Mo-Catalyzed Macrocyclic Ring Closing Metathesis in Asymmetric Synthesis. Enantioselective Total Synthesis of Sch 38516 (Fluvirucin B<sub>1</sub>),"The first enantioselective total synthesis of antifungal agent Sch 38516, also known as fluvirucin B 1, is described. The synthesis includes a convergent asymmetric preparation of amine 17 and acid 18, which are then united to afford diene 62 . Metal-catalyzed transformations play a crucial role in the synthesis of the latter moiety. Of particular note are the diastereo- and enantioselective Zr-catalyzed alkylations, a tandem Ti- and Ni-catalyzed process that constitutes a hydrovinylation reaction, and a Ru-catalyzed alcohol oxidation to afford carboxylic acid 18 . The requisite carbohydrate 38 is synthesized in a highly diastereo- and enantioselective fashion. Optical purity of the carbohydrate moiety arises from the use of the asymmetric dihydroxylation method of Sharpless; diastereochemical control is achieved through a selective dipolar [3 + 2] cycloaddition with a readily available amine serving as the chiral auxiliary. Union of the appropriately outfitted carbohydrate 71 and diene 62 through an efficient and diastereoselective glycosylation is followed by a remarkably efficient Mo-catalyzed macrocyclization that proceeds readily at room temperature.",10.1021/ja972191k,1997-10-01,0.6439973511492142
Journal of the American Chemical Society,Total Synthesis of (−)-Okilactomycin,"A highly convergent synthesis of (-)-okilactomycin is described. Key reactions of this synthesis include a strategy-level diastereoselective oxy-Cope rearrangement/oxidation sequence, a Petasis-Ferrier union/rearrangement tactic, and an efficient RCM reaction to construct the 13-membered macrocyclic ring.",10.1021/ja077569l,2007-11-13,0.6439932691060732
Angewandte Chemie International Edition,Light‐Mediated Total Synthesis of 17‐Deoxyprovidencin,"An asymmetric synthesis of the diterpenoid 17-deoxyprovidencin is described. Key steps include an aldol addition, a base-catalyzed Wipf-type furan formation, a Z-selective ring-closing metathesis for macrocyclization, a photochemical E/Z isomerization to a highly strained and conformationally restricted ring system, and the stereoselective formation of two epoxides on the ring.",10.1002/anie.201400617,2014-03-06,0.643990906798608
Tetrahedron,Studies towards the total synthesis of Sch 56036; isoquinolinone synthesis and the synthesis of phenanthrenes,,10.1016/j.tetlet.2005.07.084,2005-08-04,0.6439635290827043
Tetrahedron,Synthesis of a dicarboxylic acid receptor organized around a dioxomolybdenum core,,10.1016/0040-4039(95)02385-2,1996-02-01,0.6439550493587185
Synthesis,Synthesis of (Indol-3-yl)methanesulfonamide and its 5-Methoxy Derivative,"Two methods for the synthesis of (indol-3-yl)methanesulfonamide were elaborated based on the ‘switching off’ the reactivity of the indole nucleus in the intermediates by using indoline or indoxyl compounds. (2,3-Dihydroindol-3-yl)methanesulfonic acid was the key compound used in the indole-indoline approach and (1-acetyl-3-hydroxy-2,3-dihydroindol-3-yl)-N-(tert-butyl)methanesulfonamide was the key intermediate when 1-acetylindoxyl was used as the starting compound.",10.1055/s-2003-37354,2003-01-01,0.6439528193786727
Organic Letters,Total Synthesis of (±)-Cafestol: A Late-Stage Construction of the Furan Ring Inspired by a Biosynthesis Strategy,"An efficient bioinspired approach to the total synthesis of (±)-cafestol features a late-stage installation of the furan ring with a mild Au-catalyzed cycloisomerization. The Et2AlCl-promoted aldehyde-ene cyclization and subsequent Friedel-Crafts reaction deliver a requisite tricyclic system in gram scale with high stereo- and regioselectivity. Moreover, a highly stereoselective SmI2-mediated aldehyde-alkene radical cyclization furnishes the key bicyclo[3.2.1]octane skeleton to offer an advanced intermediate for the synthesis of other oxygenated ent-kaurene diterpenoids.",10.1021/ol500623w,2014-04-01,0.643937074077928
Organic Letters,Total Synthesis of the Conjugation-Ready Tetrasaccharide Repeating Unit of Multidrug-Resistant Pathogen <i>Pseudomonas aeruginosa</i> NCTC 8505 O-Antigen,"Herein, we report the first total synthesis of the conjugation-ready tetrasaccharide repeating unit of the O-antigen from Pseudomonas aeruginosa NCTC 8505. This work features a novel synthetic route for the incorporation of the α-linked l -galactosaminuronic acid ( l -GalpNAcA) moiety in oligosaccharide synthesis. The target molecule poses several challenging elements, including synthesis of rare sugar units, such as d -bacillosamine and l -GalpNAcA, inherently poor nucleophilicity of the axial 4-hydroxyl group of l -galactosamine, and its demanding stereoselective couplings.",10.1021/acs.orglett.5c03476,2025-09-04,0.6439240015688366
European Journal of Organic Chemistry,Stereoselective Total Synthesis of Umuravumbolide,"Abstract A simple and efficient stereoselective total synthesis of desacetylumuravumbolide ( 1a ) and umuravumbolide ( 1b ), starting from commercially available valeraldehyde has been described. The synthetic strategy involves a highly enantioselective zinc‐mediated addition of protected 2 alkyn‐1‐ol to aldehyde, a Crimmins aldol reaction, and Horner–Wadsworth–Emmons olefination as key steps.",10.1002/ejoc.201100510,2011-06-17,0.6439238118571393
Angewandte Chemie International Edition,A Concise Synthesis of Forskolin,"A 24-step synthesis of (±)-forskolin is presented, which delivered hundred milligram quantities of this complex diterpene in one pass. Transformations key to our approach include: a) a strategic allylic transposition, b) stepwise assembly of a sterically encumbered isoxazole ring, and c) citric acid-modified Upjohn dihydroxylation of a resilient tetrasubstituted olefin. The developed route has exciting potential for the preparation of new forskolin analogues inaccessible by semisynthesis.",10.1002/anie.201706809,2017-08-07,0.6439079923479736
Journal of Organic Chemistry,Synthesis of (±)- and (−)-Vibralactone and Vibralactone C,"Mander reductive alkylation of methyl 2-methoxybenzoate with prenyl bromide and hydrolysis of the enol ether afforded methyl 6-oxo-1-prenyl-2-cyclohexenecarboxylate. This was converted in five steps (reduction of the ketone, saponification, iodolactonization, ozonolysis, and intramolecular aldol reaction) to a spiro lactone cyclopentenal. An efficient first synthesis of (+/-)-vibralactone was completed by retro-iodolactonization with activated Zn, formation of the beta-lactone (vibralactone C), and reduction of the aldehyde. Except for the novel use of an iodolactone to protect both the prenyl double bond and carboxylic acid, no protecting groups were used. A similar sequence starting with asymmetric reductive alkylation of the (2S)-2-methoxymethoxymethylpyrrolidine amide of 2-methoxybenzoic acid with prenyl bromide afforded (-)-vibralactone confirming the absolute stereochemical assignment that was based on computational methods.",10.1021/jo8015743,2008-09-19,0.6439037053059723
Synthesis,"An Expedient, Scalable Synthesis of the Natural Product <scp>l</scp>-Anserine","To date, the synthesis of l-anserine has relied on the use of naturally occurring 1-methyl-l-histidine as a precursor, however its high cost prevents its use in the large-scale synthesis of l-anse­rine. With this in mind, we report herein a concise and efficient synthetic strategy, employing the 160-fold less expensive, l-histidine methyl ester dihydrochloride as a starting material, to afford the title compound in an overall yield of 88%, over four reaction steps.",10.1055/s-2007-983826,2007-08-27,0.6438994706399859
Synthesis,"Convenient Synthesis of Methyl 1-Methyl-2,4-dibromo-5-imidazolecarboxylate","All articles of this category Three syntheses of methyl 1-methyl-2,4-dibromo-5-imidazolecarboxylate (8) are presented. One proceeds from sarcosine via ring closure, bromination, and desulfurization. The second uses N -methylimidazole, polybromination, and selective halogen-metal interchange. The third and most efficient and preparatively useful route begins with diaminomaleonitrile (13) . Ring closure with triethyl orthoformate followed by methylation and hydrolysis affords 1-methyl-4,5-imidazoledicarboxylic acid (16) . Regioselective decarboxylation followed by esterification yields methyl 1-methyl-5-imidazolecarboxylate (18) . Subsequent dibromination gives the completely substituted imidazole 8 . The primary purification in this sequence is fractional sublimation of 18 after the esterification step. An overall yield of 26% is achieved from diaminomaleonitrile (13) to methyl 1-methyl-2,4-dibromo-5-imidazolecarboxylate (8) , which is a key intermediate for the synthesis of tricyclic imidazo cooked food mutagens.",10.1055/s-1988-27702,1988-01-01,0.6438755516299411
Synlett,Fragments Synthesis of A. baumannii ATCC 17961 O-Antigen,"Abstract Acinetobacter baumannii can cause many diseases including septicemia, pneumonia, meningitis, soft tissue, and urinary tract infections. Herein, we described the synthesis of one trisaccharide and two tetrasaccharide fragments derived from A. baumannii ATCC 17961 O-antigen that can be used for screening novel glyco-epitopes and for developing a synthetic carbohydrate-based vaccine against A. baumannii infection. The overall yields for the synthesis of the desired trisaccharide 1, tetrasaccharide 2, and tetrasaccharide 3 are 26.8% (8 steps), 21.6% (9 steps), and 24.5% (6 steps), respectively.",10.1055/a-2272-8163,2024-02-20,0.643874668639203
Organic Process Research & Development,Concise Preparation of a Stable Cyclic Sulfamidate Intermediate in the Synthesis of a Enantiopure Chiral Active Diamine Derivative,"A classical resolution was studied and developed from 2-benzoyl-pyridine in order to prepare SSR504734, a novel antipsychotic derivative. The key step of this route is the substitution of a sulfamidate derivative by a benzamide anion with complete inversion of configuration. The sulfamidate is prepared in a two-step procedure by reacting erythro phenyl-piperidine-2-yl-methanol derivative with thionyl chloride followed by oxidation with ruthenium oxide. This sulfamidate is an easily scalable intermediate that produce a diamine intermediate with the expected configuration.",10.1021/op500264v,2015-03-17,0.6438710483809887
Journal of the American Chemical Society,Enantioselective Total Synthesis of (−)-Pavidolide B,The enantioselective synthesis of (−)-pavidolide B ( 1 ) was achieved in a linear sequence of 10 steps. The key steps are (a) an enantioselective organocatalytic cyclopropanation; (b) a radical-based cascade annulation for the regio- and diastereo-selective synthesis of the highly functionalized lactone 3 bearing the characteristic tricyclic core and seven contiguous stereocenters; (c) a sequential ring-closing metathesis reaction and a RhCl 3 -catalyzed double bond isomerization to form the seven-membered D ring of (−)-pavidolide B.,10.1021/jacs.7b07388,2017-09-05,0.6438623658681746
Organic Letters,Synthesis of Chiral 3-Substituted Hexahydropyrroloindoline via Intermolecular Cyclopropanation,"[Structure: see text] A new and efficient synthetic route to chiral 3-substituted hexahydropyrroloindoline 18 possessing absolute configurations in accordance with indole alkaloids has been developed from readily available L-tryptophan. The key step relies on the one-pot cascade reaction of oxazolidinone 17 with diazoester, which proceeds through intermolecular cyclopropanation, ring opening, and cyclization.",10.1021/ol062489s,2006-11-23,0.6438551842415327
Tetrahedron,Synthesis of novel N-aroyl- and N-arylsulfonylisothiazole-2-imines by cyclization of thiocyanatovinylaldehyde hydrazones,,10.1016/s0040-4039(00)91960-9,1993-03-01,0.6438453462319467
Tetrahedron,The silylalkyne-Prins cyclization: a novel synthesis of 4-iododihydropyrans,,10.1016/j.tetlet.2009.11.103,2009-11-28,0.6438453462319467
European Journal of Organic Chemistry,Transition‐Metal‐Catalyzed Selective Cyclization Strategy to 2‐Substituted Benzofurans and Indoles en Route to the Oxa Analogues of Isocryptolepine,"Abstract A selective catalytic route to benzofurans and indoles from similar starting materials has been developed. A two‐step protocol that involves a transition‐metal‐catalyzed domino Sonogashira coupling between 2‐ethynylanilines and 2‐iodophenols followed by selective O ‐ and N ‐cyclizations afforded 2‐(benzofuran‐2‐yl)anilines and 2‐(indol‐2‐yl)phenols, respectively. The 2‐(benzofuran‐2‐yl)anilines were further utilized in a Lewis acid catalyzed Pictet–Spengler‐type cyclization to prepare the oxa analogues of isocryptolepine.",10.1002/ejoc.201402869,2014-09-29,0.643842676847708
Organic Letters,Total Synthesis of Asperphenins A and B,"The first total synthesis of asperphenins A and B has been accomplished in a concise, highly stereoselective fashion from commercially available materials (15 steps, 9.7% and 14.2% overall yields, respectively). The convergent route featured the judicious choice of protecting groups, fragment assembly strategy and a late-stage iron-catalyzed Wacker-type selective oxidation of an internal alkene to the corresponding ketone.",10.1021/acs.orglett.8b02652,2018-09-20,0.643835639416858
Journal of the American Chemical Society,"α,β-Unsaturated β-Silyl Imide Substrates for Catalytic, Enantioselective Conjugate Additions:  A Total Synthesis of (+)-Lactacystin and the Discovery of a New Proteasome Inhibitor","Chiral (salen)Al mu-oxo dimer 1 catalyzes the highly enantioselective conjugate addition of carbon-centered nucleophiles to alpha,beta-unsaturated silyl imides. Allyldimethylsilane-substituted imide 4 was identified as an optimal substrate, undergoing addition reactions with a variety of nitrile nucleophiles in high yield and enantiomeric excess. The silicon-containing products are synthetically useful chiral building blocks, as demonstrated by their application to an enantioselective total synthesis of the potent proteasome inhibitor (+)-lactacystin (2). Elaboration of lactam 5a to the natural product was effected in 12 steps and in 11% overall yield and proceeded through an unusual spiro beta-lactone intermediate (11). This compound was found to inhibit the chymotrypsin-like site of the 26S proteasome at similar levels to known inhibitor clasto-lactacystin beta-lactone (omuralide).",10.1021/ja061970a,2006-05-01,0.6437943564079304
Tetrahedron,A new route to 7-deazaguanine derivatives,,10.1016/s0040-4039(00)98364-3,1985-01-01,0.6437903431876537
Tetrahedron,A new route to phenanthrene derivatives,,10.1016/s0040-4039(00)76982-6,1994-07-01,0.6437903431876537
Organic Letters,Pd(II)-Catalyzed Aminofluorination of Alkenes in Total Synthesis 6-(<i>R</i>)-Fluoroswainsonine and 5-(<i>R</i>)-Fluorofebrifugine,"The total syntheses of two fluorinated alkaloids, 6-(R)-fluoroswainsonine and 5-(R)-fluorofebrifugine, are described. Both encompass (4aS,7R,8aR)-7-fluoro-5-tosylhexahydro-4H-[1,3]dioxino[5,4-b]pyridine as a key synthon which is obtained through a further optimized palladium-catalyzed aminofluorination of alkenes with high diastereoselectivity. 6-(R)-Fluoroswainsonine is synthesized from the key synthon in 14 steps, and 5-(R)-fluorofebrifugine requires a sequential 15-step transformation.",10.1021/acs.orglett.6b00030,2016-02-16,0.6437899014750078
Organic Letters,A Five-Step Synthesis of (<i>S</i>)-Macrostomine from (<i>S</i>)-Nicotine,A concise synthesis of (S)-macrostomine has been accomplished in five steps from natural nicotine in 19% overall yield via a pyridyne Diels-Alder cycloaddition reaction as the key step. A Kumada cross-coupling reaction on a 1-chloroisoquinoline intermediate provided the natural product.,10.1021/ol101887b,2010-09-22,0.6437851525058601
Organic Letters,Total Synthesis of Hyacinthacine A<sub>1</sub>and 3-<i>epi</i>-Hyacinthacine A<sub>1</sub>,"[reaction: see text] Total synthesis of hyacinthacine A(1) and its epimer at C3 is described. The synthesis includes a stereocontrolled carboazidation of a chiral allylsilane as a key step. C-Si bond oxidation and reduction of the azide, with ring-closure, complete the total synthesis, which establishes the absolute configuration of 3.",10.1021/ol050713s,2005-05-21,0.6437822796333611
Journal of Organic Chemistry,A Carbohydrate-Based Total Syntheses of (+)-Pyrenolide D and (−)-4-<i>epi</i>-Pyrenolide D,"Efficient total syntheses of (+)-pyrenolide D (5) and (-)-4-epi-pyrenolide D (6) have been achieved from a known 5-deoxy-d-xylose derivative 9 in ten steps with 19% overall yield either exclusively as 5 or as pure 5 and 6 in a 3:2 ratio. Key steps involved are one-pot epoxidation-cyclization by Corey-Chaykvosky reagent, reductive Barton-McCombie deoxygenation, and per-acid mediated oxidative spiroketalization.",10.1021/jo201570h,2011-10-21,0.6437786090515483
Synlett,A Short and Enantioselective Synthesis of Colletodiol,A 12-step enantioselective synthesis of colletodiol has been achieved using a cross-coupling metathesis and a Sharpless ­dihydroxylation as the key steps.,10.1055/s-2005-871562,2005-06-22,0.6437754197013374
Synlett,A Model Route Toward the Synthesis of Conformationally Constrained Polyhydroxylated Dipeptides from Natural Carbohydrates,"Enantiopure 6,7-diacetoxy-3-t-butoxycarbonylaminoazabicyclo[3.3.0]octan-2- one-8-carboxylic acid 14 (pyrrolizidinone amino acid) was synthesized in 14 steps and 5.8% overall yield from tri-O-benzyl-D-arabinose 5 through the formyl C-imino-sugar 9 as a key intermediate.",10.1055/s-2003-43341,2003-01-01,0.6437615357626076
Angewandte Chemie International Edition,"Enantioselective Total Synthesis of (+)‐Alstilobanine C, (+)‐Undulifoline, and (−)‐Alpneumine H","We report herein the enantioselective total synthesis of three monoterpene indole alkaloids, namely, (+)-alstilobanine C, (+)-undulifoline, and (-)-alpneumine H. The key features of our synthesis include: a) introduction of chirality via enantioselective deprotonation of a prochiral 4-substituted cyclohexanone; b) use of methoxymethyl (MOM) ether as both a hydroxyl protective group and a latent oxonium species for the formation of bridged oxepane and c) domino double reductive cyclization to build both the indole and the piperidine ring at the end of the synthesis. The synthesis confirmed the absolute configuration of these natural products assigned based on the biogenetic hypothesis.",10.1002/anie.202103580,2021-03-23,0.6437400331791358
Organic Letters,De Novo Asymmetric Synthesis of Milbemycin β<sub>3</sub> via an Iterative Asymmetric Hydration Approach,"The enantioselective synthesis of the spiroketal/macrolide natural product milbemycin beta3 has been achieved in 22 steps and 2.8% overall yield from an achiral dienoate. The spiroketal ring system was installed by three sequential asymmetric hydrations followed by sprioketalization. Both the absolute and relative stereochemistry of milbemycin beta3 was introduced by two Sharpless asymmetric dihydroxylations, two pi-allylpalladium-catalyzed reductions, and an iridium-catalyzed hydrogen migration/Claisen rearrangement to install the C-12 stereocenter.",10.1021/ol061439k,2006-08-01,0.6437113003013566
Journal of the American Chemical Society,Total Synthesis of UCS1025A,The enantioselective total synthesis of the telomerase inhibitor UCS1025A has been accomplished. The key transformation involves a remarkable boron Reformatsky coupling of iodolactone 13 and aldehyde 17.,10.1021/ja0574567,2005-12-16,0.6437043001017152
Synthesis,Synthetic Access to 2-Amido-5-aryl-8-methoxy-triazolopyridineand 2-Amido-5-morpholino-8-methoxy-triazolopyridine Derivativesas Potential Inhibitors of the Adenosine Receptor Subtypes,"Two versatile and complementary synthetic strategies towards 2-amido-5-aryl-8-methoxy-triazolopyridine derivatives and 2-amido-5-morpholino-8-methoxy-triazolopyridine derivatives in five steps are presented. The key step in each synthetic route can be constituted as the formation of the respective triazolopyridine derivative precursors in 78% and 57% yield, respectively, through an intermediately formed 4H-[1,2,4]oxadiazol-5-one. The final Suzuki coupling/amidation allowed the straightforward access to the desired triazolopyridine derivatives which have not been described previously. Notably, these triazolopyridine-scaffold bears three vectors of diversity which offer maximum flexibility in design and combinatorial synthesis of molecules with a potentially useful inhibitory activity towards adenosine receptor subtypes.",10.1055/s-2003-40874,2003-08-01,0.6436997911584105
Journal of Organic Chemistry,"Catalytic Enantioselective and Divergent Total Synthesis of (+)-10-Oxocylindrocarpidine, (+)-Cylindrocarpidine, (−)-<i>N</i>-Acetylcylindrocarpinol, and (+)-Aspidospermine","The catalytic enantioselective and divergent total syntheses of Aspidosperma alkaloids (+)-10-oxocylindrocarpidine 7, (+)-cylindrocarpidine 1, (-)-N-acetylcylindrocarpinol 6, and (+)-aspidospermine 8 have been accomplished in 11 steps from a common precursor (15) on the basis of a highly concise route. The route features three metal-catalyzed reactions, including the key Pd-catalyzed decarboxylative asymmetric allylation of carbazolones developed in our laboratory. Our syntheses, using a combination of C-H activation, enantioselective catalysis, and collective synthesis, represent the first total synthesis of 10-oxocylindrocarpidine and the first asymmetric total synthesis of cylindrocarpidine and N-acetylcylindrocarpinol.",10.1021/jo402741g,2014-02-21,0.6436806027159186
Tetrahedron,A formal total synthesis of erythromycin A. 2. A convergent synthesis of Woodward's carbamate intermediate,,10.1016/s0040-4039(00)86717-9,1988-01-01,0.6436673815232714
Tetrahedron,Facile and rapid route for the synthesis of novel norstatine analogs via PADAM-cyclization methodology,,10.1016/j.tetlet.2011.12.073,2011-12-29,0.6436589870743589
Organic Process Research & Development,"The Process Development of a Scaleable Route to the PDE5 Inhibitor UK-357,903","A case history is outlined for the development of a scaleable route to the drug candidate UK-357,903. Despite the partial structural similarities to those of sildenafil (Viagra), the introduction of the central pyridine moiety within UK-357,903 had a significant impact on the commercial process. In particular, the triply activated 2-alkoxy pyridyl moiety of UK-357,903 is much more susceptible to nucleophilic attack than the 2-ethoxy phenyl moiety of sildenafil, necessitating the development of new chemistry. Particular items of note are (i) the new six-step route to the advanced 2-ethoxy-5-(4-ethylpiperazinylsulfonyl)nicotinic acid intermediate and the subsequent telescoping to a two-pot process, (ii) the telescoping of the two steps from N -[3-carbamoyl-5-ethyl-1-(2-pyridylmethyl)-1 H -pyrazol-4-yl]-2-ethoxy-5-(4-ethyl-1-piperazinylsulfonyl)nicotinamide to UK-357,903 to a single step, with the additional use of a hydroxide trapping agent to give an ambient pressure process yielding clinical quality product, and (iii) the introduction of process modifications to allow for the use of teratogenic 2-methoxyethanol, as both reagent and solvent, in the penultimate process step.",10.1021/op0200468,2002-09-17,0.6436516747788146
Journal of Organic Chemistry,Formal Synthesis of (−)-Neopeltolide Featuring a Highly Stereoselective Oxocarbenium Formation/Reduction Sequence,"The formal synthesis of the unnatural (-)-neopeltolide core is discussed in detail. Efficient application of the Evans' protocol for the synthesis of 1,3-syn-diols via an intramolecular hetero-Michael addition followed by reductive deprotection of the resulting benzylidene acetal allowed for swift access to the delta-lactone. Central to the synthetic approach is a tandem nucleophilic addition-diastereoselective axial reduction of an in situ generated oxocarbenium cation to assemble the beta-C-glycoside moiety of the neopeltolide core.",10.1021/jo100443h,2010-05-26,0.643649112579507
Journal of Organic Chemistry,Synthesis of Chiral Aminophosphines from Chiral Aminoalcohols via Cyclic Sulfamidates,"Protic aminophosphines with multiple chiral centers were synthesized in good yields and high purity by the nucleophilic ring-opening of N-protected cyclic sulfamidates with metal phosphides, followed by hydrolysis and deprotection. This synthetic approach is clean, scalable, and high yielding. The method provides an efficient alternative route for the synthesis of chiral aminophosphines.",10.1021/jo902302c,2009-12-23,0.6436199780827545
Synthesis,Enantiodivergent Syntheses of Pantolactone and Pantothenic Acid from d-Mannitol,"Efficient synthetic routes to both the enantiomers of pantolactone and pantothenic acid have been developed starting from d -mannitol-based d -glyceraldehyde acetonide through its conversion into a protected pantoic acid intermediate followed by either cyclization or amide bond formation with a β-amino ester, and subsequent appropriate deprotection.",10.1055/s-0031-1290489,2012-03-05,0.6435863087314718
Angewandte Chemie International Edition,A Short Route to α‐Tocopherol,"Short and sweet: A simple and practical route to α-tocopherol is described (see scheme; TES=triethylsilyl). The key step is a remarkably diastereoselective domino aldol/oxa-Michael reaction, which is promoted by proline derivative 1.",10.1002/anie.200801765,2008-06-24,0.6435787841931948
Journal of Organic Chemistry,Formal synthesis of clavicipitic acid based on biosynthetic proposal,"The formal synthesis of clavicipitic acid is reported. The synthetic strategy is based on the biosynthetic hypothesis of Floss which involves the azepino ring ring closure of 10-hydroxy($\gamma$,$\gamma$-dimethylallyl)tryptophan. This ring enclosure involves an intramolecular, nucleophilic attack of an amine on a protein-activated hydroxyl group. The starting material for the synthesis is indole-4-carboxaldehyde. An alternate proposal for the synthesis involving a proton-driven rearrangement of a 10-membered macrocyclic amine to the azepino was not able to be realized owing to the inaccessibility of the requisite substrate necessary for implementation of this strategy. Alternate approaches for the synthesis of this substrate are considered and preliminary synthetic work is presented. The most efficient route to the azepino system employs a proton-catalyzed ring closure and produces the simple dehydration product methyl-4-(3-methyl-1,3-butadien-1-yl)-3-(2-amino-2-carbomethoxy-3-indolyl)propionate in addition to the desired amination product. Attempts at an intramolecular Mitsunobu coupling were unsuccessful. The two dehydration products were demonstrated to be interconvertible upon acidic catalysis. Implications of the diene by-product to the biosynthesis of the Ergot alkaloids are considered. A comprehensive review of clavicipitic acid including its isolation, structure elucidation, biosynthesis, and synthesis is presented.",10.1021/jo00256a039,1988-10-01,0.6435757046872834
Organic Process Research & Development,"A Second-Generation Route to the Cereblon Fragment of ARV-471, Vepdegestrant","A second-generation route to the cereblon fragment of ARV-471, vepdegestrant, an orally available proteolysis targeting chimera (PROTAC) submitted to the FDA for NDA review to treat metastatic breast cancer, is reported. With the new, more convergent route, the chiral cyclic imide moiety is installed as a key fragment via reductive amination with a linker fragment.",10.1021/acs.oprd.5c00271,2025-10-13,0.6435648541464446
Organic Letters,Asymmetric Total Syntheses of Euphol and Tirucallol,"Asymmetric de novo syntheses of euphol and tirucallol have been accomplished by way of a concise sequence of chemical steps featuring several modern stereoselective transformations. The preparative solution described for these complex problems in natural product synthesis departs significantly from biomimetic polyene cyclization chemistry, which has been leveraged to address related tetracyclic triterpenoid targets. In particular, a diastereoselective Friedel–Crafts-type cyclization was employed to establish a tetracycle bearing a stereodefined quaternary center at C9 (steroid numbering) that provided access to intermediates of relevance for introducing the C10 and C14 quaternary centers by sequential stereospecific 1,2-alkyl shifts (C9 → C10 and C15 → C14). Finally, the stereodefined C17 side chain was introduced in a single step by late-stage stereoselective conjugate addition to an intermediate possessing a D-ring enone. Notably, these de novo asymmetric syntheses are the first of their kind, providing completely synthetic access to enantiodefined euphane and tirucallane systems. Overall, each synthesis has been accomplished in fewer than 20 linear chemical steps from a simple Hajos–Parrish-derived ketone through a sequence that features just 15 chromatographic operations.",10.1021/acs.orglett.3c02187,2023-07-21,0.6435419417006716
Organic Letters,Short Route to Cassane-Type Diterpenoids: Synthesis of the Supposed Structure of Benthaminin 1,"A short route toward aromatic cassane diterpenes from labdane terpenoids has been developed. In the key step, the aromatic ring with the oxygenated function at C-12 and the characteristic carbon group at C-14 of the target compounds is elaborated via a Diels-Alder/aromatization sequence of a furanosesquiterpene and methyl propiolate. On this basis, the synthesis of the proposed structure of benthaminin 1 from trans-communic acid has been achieved. The physical properties of the synthetic compound are somewhat different from those reported for the natural product.",10.1021/acs.orglett.6b03121,2016-11-09,0.6435301438775525
Organic Letters,Concise Synthesis of the Core Structures of Saundersiosides,"A divergent synthesis of three core pentacyclic lactones of nine rearranged cholestane sapogenins, saundersiosides A-H (1-8) and candicanoside A (9), is reported. Key features include a one-flask CBS reduction/Brown hydroboration-oxidation, a SmI2-mediated intramolecular Reformatskii reaction, and an intramolecular transesterification. This synthesis provides a general strategy and key precursors for the collective synthesis of natural and designed saundersiosides. An efficient formal synthesis of candicanoside A is also achieved.",10.1021/acs.orglett.5b00821,2015-05-04,0.6435269810659597
Journal of the American Chemical Society,Synthesis of Dimeric Securinega Alkaloid Flueggeacosine B: From Pd-Catalyzed Cross-Coupling to Cu-Catalyzed Cross-Dehydrogenative Coupling,"We completed the synthesis of dimeric high-oxidation-state securinega alkaloid flueggeacosine B via two synthetic routes from allosecurinine. The first-generation synthesis (seven overall steps) involved a Liebeskind-Srogl cross-coupling reaction for the union of two functionalized fragments, the organostannane and the thioester. As a means to further streamline the synthetic route, we have developed a visible-light-mediated Cu-catalyzed cross-dehydrogenative coupling (CDC) reaction between an aldehyde and an electron-deficient olefin. This enabled the second-generation synthesis of flueggeacosine B from allosecurinine in four overall steps. The newly developed CDC reaction paves a direct way to a conjugated dicarbonyl moiety, a ubiquitous structural moiety present in various natural products.",10.1021/jacs.2c03861,2022-05-16,0.643524550653969
Journal of Organic Chemistry,Total Synthesis and Determination of the Absolute Configuration of Coscinosulfate. A New Selective Inhibitor of Cdc25 Protein Phosphatase,"The first total synthesis of coscinosulfate 1, a metabolite isolated from a sea sponge, starting from (+)-sclareolide 3 is described. The convergent synthesis strategy relies on the coupling of sulfone 21 with the bromide 26. The sulfone fragment 21 was obtained by successive asymmetric aldol reaction with aldehyde 2 to introduce the stereocenters at C-12 and C-13, followed by one-carbon homologation via Horner-Wadsworth-Emmons olefination. The selective sulfatation at C-12 was accomplished through the quinone intermediate 31 obtained by selective oxidation of hydroquinone 30; this, when followed by reduction, furnished the desired coscinosulfate 1. X-ray analysis of the intermediate aldehyde 18 confirmed the proposed structure.",10.1021/jo010154c,2001-10-03,0.6435206308400602
Organic Process Research & Development,Preparation of the HIV Attachment Inhibitor BMS-663068. Part 3. Mechanistic Studies Enable a Scale-Independent Friedel–Crafts Acylation,"During the development of a Friedel–Crafts acylation for the preparation of a key pyrrole intermediate in the synthesis of the HIV attachment inhibitor, BMS-663068-03, a significant scale dependence was found. A precipitous drop in yield was observed for the acylation of a protected pyrrole with chloroacetyl chloride upon scale-up. Spectroscopic studies to mitigate this scale dependence led to the identification of the complex effect of dissolved hydrogen chloride (HCl) as well as the poor reactivity of the acylating agent, chloroacetyl chloride. At this point, the counterintuitive choice to switch to a longer, but scale-independent, three-step route was made. By changing the acylating agent to acetyl chloride, a more robust process was obtained. Rapid development of a high yielding α-chlorination then provided the common α-chloroketone intermediate required to generate the desired α-amide ketopyrrole. The improved yield and scalability of this three-step process supported the addition of one linear step to the route, and it was demonstrated successfully at scale.",10.1021/acs.oprd.7b00115,2017-08-09,0.6435112521612018
Tetrahedron,Synthetic route for 14C-labeling of a bioactive lipid a analogue,,10.1016/0040-4039(95)01863-d,1995-11-01,0.6435046641709233
Angewandte Chemie International Edition,"The Enantioselective Synthesis of Eburnamonine, Eucophylline, and 16′‐<i>epi</i>‐Leucophyllidine","A synthetic approach to the heterodimeric bisindole alkaloid leucophyllidine is disclosed herein. An enantioenriched lactam building block, synthesized through palladium-catalyzed asymmetric allylic alkylation, served as the precursor to both hemispheres. The eburnamonine-derived fragment was synthesized through a Bischler-Napieralski/hydrogenation approach, while the eucophylline-derived fragment was synthesized by Friedländer quinoline synthesis and two sequential C-H functionalization steps. A convergent Stille coupling and phenol-directed hydrogenation united the two monomeric fragments to afford 16'-epi-leucophyllidine in 21 steps from commercial material.",10.1002/anie.202106184,2021-05-26,0.643503690567251
Journal of Organic Chemistry,"SmI<sub>2</sub>-Mediated Radical Coupling Strategy to Securinega Alkaloids: Total Synthesis of (−)-14,15-Dihydrosecurinine and Formal Total Synthesis of (−)-Securinine","The asymmetric total synthesis of (-)-14,15-dihydrosecurinine and the formal total synthesis of (-)-securinine were accomplished starting from an easily available malimide. A concise SmI2-mediated radical coupling strategy has been developed to construct the bridged α-hydroxy 6-azabicyclo[3.2.1]octanone in four steps with high diastereoselectivity.",10.1021/jo502522x,2014-12-15,0.6434526349470628
Journal of Organic Chemistry,Asymmetric Synthesis of the Cytotoxic Marine Natural Product (+)-Awajanomycin and Its C-11 Epimer,"Full details of the convergent synthetic approach to awajanomycin, and the first total syntheses of the marine natural product (+)-awajanomycin (1) and its C-11 epimer 38 by an improved 13-step approach, are described. The key elements of the synthetic strategy resided in the use of (R)-18 as the chiral building block to construct the gamma-lactone-delta-lactam core 3 and cross-olefin metathesis as the key reaction to couple the latter with the allylic alcohol segment (R- or S-4). The efficient construction of the core 3 was realized by taking advantage of the inherent multiple reactivities of the chiral building block (R)-18. A highly diastereoselective one-pot transformation of 6 to 26 was achieved in a ""one stone four birds"" manner. On the other hand, enantioselective synthesis of both enantiomers of the segment 4 has been undertaken by an alternative and more efficient two-step procedure. Both awajanomycin (1) and 11-epi-awajanomycin 38 have been synthesized with overall yields of 3.8% and 3.6%, respectively. Quantum chemical calculations were undertaken to reveal the low reactivity of compound 27 toward methoxycarbonylation and to get an insight into the favored conformations of the intermediates 25-27. In addition, the geometry of the side product 39 arising from the homocoupling of the allylic alcohol moiety 4 was revised as E, and an unusual cyclopropanation reaction was discovered.",10.1021/jo100744c,2010-05-27,0.6434504288745595
Organic Letters,Synthetic Study on Tetrapetalones: Stereoselective Cyclization of <i>N</i>-Acyliminium Ion To Construct Substituted 1-Benzazepines,"The synthesis of the tetracyclic core of complex antibiotic tetrapetalones has been achieved in three steps starting from the simple intermediate gamma-hydroxy amide, which can be accessed through a high-yielding six-step sequence. The successful synthesis relies on a novel strategy based on the N-acyliminium ion cyclization.",10.1021/ol901349b,2009-08-13,0.6434415761415697
European Journal of Organic Chemistry,Stereoselective Synthesis of Substituted Piperidines – Total Synthesis and Absolute Configurations of (+)- and (–)-Dienomycin C,"The first total asymmetric synthesis and the attribution of the absolute configurations of (+)-dienomycin C (1), an alkaloid isolated from a Streptomyces strain, are reported. This compound was prepared in six steps from the enantiopure tricarbonyl(dienal)iron complex (+)-4 which is easily obtained by separating preformed diastereomers, starting from phenylpentadienoic acid and (S)-methyl mandelate.",10.1002/(sici)1099-0690(199907)1999:7<1517::aid-ejoc1517>3.0.co;2-h,1999-07-01,0.6434174477729047
Journal of Organic Chemistry,"Scalable Asymmetric Synthesis of MK-8998, a T-Type Calcium Channel Antagonist",Two scalable and efficient synthetic routes for the synthesis of a T-type calcium channel antagonist MK-8998 were developed from a simple pyridine building block. The key step to set the stereochemistry relied on either chiral rhodium catalyst-mediated asymmetric hydrogenation of an enamide or transamination of an arylketone that provided the corresponding product in high enantioselectivity and high yield.,10.1021/acs.joc.1c01795,2021-09-28,0.6434132764312029
Tetrahedron,A concise total synthesis of (−)-dehydroclausenamide utilizing the novel formation of cis-epoxide as the key step,,10.1016/j.tetlet.2003.09.229,2003-12-01,0.6434090196793093
Journal of Organic Chemistry,Preparation of 8-Substituted Xanthine CVT-124 Precursor by Late Stage Pyrimidine Ring Closure,"To develop a novel route for the scaleable synthesis of the chiral xanthine CVT-124 (1, aka. BG9719), a method for the late stage pyrimidine ring closure of the nitrogen-protected endo 2-norbornenyl imidazole 3 was developed. The three-component coupling of benzylamine, 2-cyanoglycine ethyl ester (4), and methyl 5-norbornene-2-carboximidate hydrochloride (5) was demonstrated to achieve 3 in 23-46% isolated yields. The imidazole 3 was then elaborated to construct the N-benzyl xanthine 2 as a 1:1 mixture of exo and endo isomers, which were separable at this stage by chromatography. The nitrogen-protected endo xanthine 2 is a key intermediate in the synthesis of CVT-124.",10.1021/jo015925r,2001-12-07,0.643407896602023
Synthesis,"Synthesis of Methyl 7,9-Dimethyl-5-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepine-1-carboxylate and Its Analogues","A high-yielding five-step synthesis of the title compound, methyl 7,9-dimethyl-5-oxo-2,3,4,5-tetrahydro-1 H -benzo[ b ]azepine-1-carboxylate, starting from 2,4-dimethylaniline was developed. This synthesis involved N-alkylation of 2,4-dimethyl­aniline with ethyl 4-bromobutyrate to obtain ethyl 4-[(2,4-dimethylphenyl)amino]butanoate. Carbamoylation of the latter followed by hydrolysis of the resulting ester provided 4-[(2,4-dimethylphenyl)(methoxycarbonyl)amino]butanoic acid. Activation of the carboxylic acid using thionyl chloride followed by intramolecular cyclization via a Friedel–Crafts reaction using aluminum trichloride provided the title compound in good yield. Analogues of the title compound were also prepared similarly.",10.1055/s-0034-1378279,2014-06-24,0.6433194700072912
Tetrahedron,The improved synthesis of 7-oxygenated indoles by Fischer indolization and its application to the first total synthesis of eudistomidin-A,,10.1016/s0040-4039(01)93722-0,1989-01-01,0.6433157912789305
Synthesis,Regiospecific Synthesis of Novel 6-Amino-5-hydroxypyridazin-3(2<i>H</i>)-ones,"The synthesis of a novel class of 6-amino-5-hydroxy­pyridazin-3(2H)-ones (3-oxo-2,3-dihydropyridazines) is described. These compounds also contain an ethoxycarbonyl moiety at the 4-position of the pyridazinone ring. They are prepared in good to moderate yields (30-72%) by the condensation of disubstituted amines with (alkylhydrazono)- or (arylhydrazono)(chloro)acetates followed by subsequent acylation with ethyl malonyl chloride and Dieckmann cyclization. An initial assessment of the scope and limitations of the new methodology is described along with the novel synthesis of several (alkylhydrazono)(chloro)acetate substrates utilized in the pyridazinone preparations.",10.1055/s-2008-1032157,2008-02-01,0.6432831715888503
Organic Letters,Total Synthesis of Pareitropone via Radical Anion Coupling,A concise (9-step) synthesis of the tropoloisoquinoline alkaloid pareitropone has been achieved starting from 2-bromoisovanillin. The key step features oxidative cyclization of a readily available phenolic nitronate for the convenient construction of the fused tropone ring. This work underscores the synthetic utility of intramolecular oxidative coupling reactions of phenolic nitronates.,10.1021/ol1017849,2010-08-10,0.6432796904928372
Organic Letters,Enantioselective Total Synthesis of (−)-α-Kainic Acid,"An enantioselective total synthesis of (-)-alpha-kainic acid is described. Key steps are an Ir-catalyzed allylic amination with a propargylic amine to provide an enyne and a diastereoselective intramolecular Pauson-Khand reaction. Subsequent steps involve a Baeyer-Villiger reaction, reduction of the resulting lactone, and direct Jones oxidation of a silyl ether.",10.1021/ol1001076,2010-02-11,0.6432781303529913
Journal of Organic Chemistry,Squaric Acid Ester-Based Total Synthesis of Echinochrome A,"The total synthesis of echinochrome A is described. Both key intermediates 5 and 8 were efficiently prepared from diisopropyl squarate 7. Nucleophilic addition of aryllithium 8 to 5, followed by thermal ring-expansion/cyclization of the 1,2-adduct 4, furnished hydroquinone 3. Oxidation and full deprotection of 3 gave the title compound.",10.1021/jo016034m,2002-02-05,0.6432729554592885
Tetrahedron,Improved synthesis of quinine alkaloids with the Teoc protective group,,10.1016/j.tetlet.2005.06.171,2005-08-03,0.643265303568827
Synthesis,"One-Step Synthesis of<i>N</i>,<i>N</i>′-Methylene-2,2′-Azapyridocyanines","All articles of this category A facile one-pot synthesis of N , N ′-methylene-2,2′-azapyridocyanines is described.",10.1055/s-1986-31652,1986-01-01,0.6432563384623587
Organic Letters,Facile and Efficient Total Synthesis of (+)-Preussin,"[structure] The enantioselective total synthesis of (+)-preussin, a potent antifungal agent, has been achieved. The key steps are a Pd(0)-catalyzed oxazoline-forming reaction from L-phenylalanine, hydrogenolysis, and subsequent diastereoselective reductive cyclization of the intermediate aminoketone to pyrrolidine using Pearlman's catalyst.",10.1021/ol000289p,2000-11-16,0.6432546047931706
Organic Letters,Total Synthesis of (+)-7-Deoxypancratistatin from Furan,"A new total synthesis of (+)-7-deoxypancratistatin 1 has been accomplished in 19 steps (8% overall yield) from two readly available compounds, furan and trans-1,2-bis(phenylsulfonyl)ethylene.",10.1021/ol000268v,2000-10-14,0.6432486791542504
Tetrahedron,Synthesis of the parent compound of isobacteriochlorins - a diminution of the π-system of porphins,,10.1016/s0040-4039(00)87325-6,1982-01-01,0.6432381171173766
Tetrahedron,Dimeric surfactants: First synthesis of an asymmetrical gemini compound,,10.1016/s0040-4039(97)10835-8,1998-03-01,0.6432381171173766
Journal of Organic Chemistry,Enantioselective Total Synthesis of (+)-Scuteflorin A Using Organocatalytic Asymmetric Epoxidation,"We report the first enantioselective total synthesis of (+)-scuteflorin A in 14% overall yield, employing a chiral iminium salt to effect an organocatalytic asymmetric epoxidation of xanthyletin in >99% ee as the key step.",10.1021/jo2021407,2011-12-02,0.6432062785151145
Angewandte Chemie International Edition,Total Synthesis of (−)‐Lycoposerramine‐S,"To the core: The first total synthesis of (−)-lycoposerramine-S has been accomplished in 14 steps. The synthesis features the facile construction of the tetracyclic core through an intramolecular 1,3-dipolar cycloaddition of an azomethine ylide, with unexpected stereoselectivity, an 5-exo-trig radical cyclization, and an alkylation of p-nosyl (Ns) amide. TBS=tert-butyldimethylsilyl.",10.1002/anie.201206863,2012-10-15,0.6432011688732956
Synlett,"Synthesis of 2′,3′-Dideoxy-2′-Fluoro-4′-Thionucleosides from a Fluoroxanthate","The synthesis of a thiobutyrolactone as precursor of modified nucleosides is reported from a fluoroxanthate and a protected allylic alcohol. This approach opens a new and straightforward route for the synthesis of 2′,3′-dideoxy-2′-fluoro-4′-thiothymidine derivatives in few steps, including the formation of a fluorothiolactone and a Vorbrüggen thymine base alkylation reaction.",10.1055/s-2008-1042904,2008-03-20,0.6431986996529929
Synthesis,"New Route for the Synthesis of (22<i>S</i>,23<i>S</i>)-28-Homobrassinolide","A new and highly efficient synthesis of (22S,23S)-28-homobrassinolide (3) has been achieved. (2α,3α,22S,23S)-Tetrahydroxy-5α-stigmastan-6-one (4), a key intermediate for the synthesis of 3, and (2α,3α)-dihydroxy-5α-stigmast-22-en-6-one (6), a versatile intermediate for the synthesis of 3, and several naturally occurring brassinosteroids have been obtained in excellent yield from stigmasta-2,(22E)-dien-6-one (5) by catalytic RuO4 hydroxylation. Sodium perborate, a cheap and large-scale industrial chemical is used for Baeyer-Villiger oxidation of B-ring ketone 9 to its lactone 10.",10.1055/s-2003-37346,2003-01-01,0.643194280156072
Journal of Organic Chemistry,"Design and Effective Synthesis of the First 4-Aza-2,3-didehydropodophyllotoxin Rigid Aminologue: A <i>N</i>-Methyl-4-[(3,4,5-trimethoxyphenyl)amino)]-1,2-dihydroquinoline-lactone","The first N1-alkyl-4-amino-1,2-dihydroquinoline-lactone has been prepared by a five-step sequence in a 51% overall yield via the corresponding furo[3,4-b]quinolin-1(3H)-one. A new practical synthesis of this intermediate was carried out using versatile, commercially available starting materials and constitutes the shortest and highest yielding route. These synthetic pathways could be widened with a view toward the preparation of different substituted derivatives, which could be considered as rigid aminologues of 4-aza-2,3-didehydropodophyllotoxins.",10.1021/jo800166b,2008-04-02,0.6431635917008973
Organic Letters,A Convergent Synthesis of the Proposed Structure of Antitumor Depsipeptide Stereocalpin A,"The total synthesis of the proposed structure of anticancer agent stereocalpin A is described. The synthesis features a diastereoselective synthesis of a 5-hydroxy-2,4-dimethyl-3-oxooctanoic acid unit with asymmetric anti- and syn-aldol reactions as the key steps. Initial cycloamidation led to complete epimerization at the C-11 stereocenter due to unique steric constraints in the 12-membered depsipeptide ring. A late-stage methylation strategy led to the synthesis of the proposed structure of stereocalpin A.",10.1021/ol900412u,2009-04-08,0.6431634224097718
Synthesis,A Practical Synthesis of Homoallylic Diene Halides: Versatile Synthons for the Preparation of the Taxane A-Ring System,"Abstract A concise and efficient synthesis of two homoallylic halides, which are useful precursors for the preparation of the taxane A-ring system is reported. Contrary to the synthetic routes reported in the literature, this procedure does not employ expensive tetramethylethylene as a starting material. The synthetic route uses readily available and inexpensive ethyl acetoacetate, 1,2-dibromoethane, methyltriphenylphosphonium iodide and methylmagnesium bromide as starting materials. The key step in the synthesis is the acid-mediated ring opening of a cyclopropyl tertiary alcohol to afford the corresponding homoallylic diene halides. The corresponding Grignard reagent, derived from the bromide, is used in the synthesis of an enone previously used as a precursor of taxadienone by reaction with the enol ethyl ether of 1,3-cyclohexanedione.",10.1055/a-2215-3546,2023-11-21,0.6431447498416915
Organic Process Research & Development,Convergent Asymmetric Synthesis of Two Complex TRPV1 Antagonists,"The convergent scale-up synthesis of two complex TRPV1 antagonists to support exploratory toxicology studies is described. Both compounds contain three chiral centers introduced by asymmetric synthesis with chiral control being critical for the success of the project. Preparation of the key cyclopropyl intermediate utilised an asymmetric cyclopropanation using thermally unstable ethyl diazoacetate. Ellman’s auxiliary was used to synthesize the chiral α-methyl benzylamine fragments. This paper highlights some of the key synthetic challenges, processing issues, and safety aspects from the scale-up of this chemistry.",10.1021/op200177b,2011-08-01,0.6431383998328963
Journal of the American Chemical Society,Synthesis of Heparin Oligosaccharides,"An efficient preparation of rare 2-O-benzoyl-3-O-benzyl-1,6-anhydro-beta-l-idopyranose from commercially available diacetone alpha-d-glucose in five straightforward steps is described here. With this key building block in hand, the total syntheses of heparin oligosaccharides with three, five, seven, and nine sugar units are successfully carried out.",10.1021/ja038244h,2003-12-19,0.643136064159017
Synthesis,"Concise Total Synthesis of Helicascolides A, B, and C","The concise total synthesis of helicascolides A, B, and C has been achieved in seven steps starting from commercially available tiglic aldehyde [( E )-2,3-dimethylacrylaldehyde]. Oppolzer’s sultam aldol, Mukaiyama aldol, and Dess–Martin periodinane oxidation reactions are the key steps involved in the target synthesis.",10.1055/s-0032-1316861,2013-03-14,0.6431327637567891
Organic Letters,"Highly Convergent Total Synthesis and Assignment of Absolute Configuration of Majusculamide D, a Potent and Selective Cytotoxic Metabolite from <i>Moorea sp.</i>","The total synthesis of majusculamide D (MJS-D) is described, a lipopentapeptide originally isolated from Lyngbya majuscula and reisolated from a Moorea sp. MJS-D possesses selective and potent cancer cell toxicity. A scalable and convergent strategy with a minimal number of purifications produced significant quantities of MJM-D for in vivo evaluations. The absolute configuration of the 1,3-dimethyl-octanamide motif was determined by synthesis of this fragment via ZACA chemistry.",10.1021/acs.orglett.8b04050,2019-01-23,0.6431327110673863
Organic Process Research & Development,Development of a Safe and Economical Synthesis of Methyl 6-Chloro-5-(trifluoromethyl)nicotinate: Trifluoromethylation on Kilogram Scale,"Reported herein is a safe and economical synthesis of methyl 6-chloro-5-(trifluoromethyl)nicotinate, an intermediate in the synthesis of novel anti-infective agents. The key to this process is the trifluoromethylation of an aryl iodide using an inexpensive methyl chlorodifluoroacetate (MCDFA)/KF/CuI system, with an emphasis on the development work which led to this effective process.",10.1021/op400061w,2013-05-09,0.6431294236503863
Tetrahedron,"Synthesis of the taxane diterpenes: construction of A BC ring intermediate for taxane synthesis. Swindell, C.S.; de Solms, S.J. Tetrahedron Lett. 1984, 25, 3801.",,10.1016/s0040-4039(00)98526-5,1985-01-01,0.6431118256630589
Organic Process Research & Development,Preparation of 5-(2-Methoxy-4-nitrophenyl)oxazole:  A Key Intermediate for the Construction of VX-497,"A process for the multigram preparation of 5-(2-methoxy-4-nitrophenyl)oxazole, a key intermediate for the preparation of the hepatitis C drug candidate VX-497 (merimepodib), has been achieved in good yield from a commercially available dye. Early studies focused on the preparation of the requisite aldehyde by the Beech reaction. A second approach utilized a palladium (0)-catalyzed formylation of an aryl diazonium species, which was followed by condensation of the aldehyde with tosylmethyl isocyanide (TosMIC) to provide the required oxazole. This two-step method has been carried out to provide multigram samples of this key intermediate in 75% overall yield and >95% purity from the commercially available Fast Red B tetrafluoroborate salt.",10.1021/op025546f,2002-07-25,0.6431008401920661
Organic Letters,Synthesis of Maremycins A and D<sub>1</sub> via Cycloaddition of a Nitrone with (<i>E</i>)-3-Ethylidene-1-methylindolin-2-one,A concise synthesis of maremycins A and D1 has been accomplished via cycloaddition of a chiral cyclic nitrone with ( E)-3-ethylidene-1-methylindolin-2-one as a key step. This synthesis clarifies the stereochemistry of the maremycins and is suitable for large-scale synthesis for biological screening.,10.1021/ol800515w,2008-04-16,0.643099701007923
Synlett,Synthesis of the C1-C13 Fragment of (+)-Callipeltoside A,The synthesis of the C1-C13 fragment of (+)-callipeltoside A has been achieved in 12 steps with an overall yield of 11%.,10.1055/s-2007-980367,2007-05-23,0.6430666743441796
Journal of Organic Chemistry,Stereocontrolled Total Synthesis of Hemibrevetoxin B,"The stereocontrolled total synthesis of hemibrevetoxin B ( 1 ) has been achieved in 56 steps and 0.75% overall yield from d -mannose. The intramolecular reaction of γ-alkoxyallylstannane with aldehyde is a key step for the present total synthesis. Thus, the BF 3 ·OEt 2 -mediated reaction of 24 gave 6 as a sole product. We encountered difficulty in the synthesis of γ-alkoxyallylstannane 30 from the corresponding allyl ether 29 in which the γ-alkoxy substituent became sterically quite bulky. This problem was solved by developing the acetal cleavage method for the synthesis of γ-alkoxyallylstannanes. The cyclization of 38 proceeded smoothly to give the key intermediate 5 in a highly stereoselective manner. Construction of the α-vinyl aldehyde and ( Z )-diene moieties were performed using Nicolaou's protocol.",10.1021/jo9807619,1998-08-28,0.6430487718716201
Journal of Organic Chemistry,Total Synthesis of Coriandrin,"Coriandrin, an antiviral agent, has been synthesized in nine steps from diketone 3. The key steps in the synthesis include an eficient aromatization reaction using N-bromosuccinimide and a palladium-mediated coupling of a benzylic bromide with a vinyl stannane.",10.1021/jo00096a013,1994-08-01,0.6430439181429146
Angewandte Chemie International Edition,"Concise, Enantioselective, and Versatile Synthesis of (−)‐Englerin A Based on a Platinum‐Catalyzed [4C+3C] Cycloaddition of Allenedienes","A practical synthesis of (-)-englerin A was accomplished in 17 steps and 11 % global yield from commercially available achiral precursors. The key step consists of a platinum-catalyzed [4C+3C] allenediene cycloaddition that directly delivers the trans-fused guaiane skeleton with complete diastereoselectivity. The high enantioselectivity (99 % ee) stems from an asymmetric ruthenium-catalyzed transfer hydrogenation of a readily assembled diene-ynone. The synthesis also features a highly stereoselective oxygenation, and a late-stage cuprate alkylation that enables the preparation of previously inaccessible structural analogues.",10.1002/anie.201607348,2016-10-13,0.643043249572447
Synthesis,"Rhodium(III)-Catalyzed C–H Activation-Based First Total Synthesis of 6-O-Methyl Anciscochine, an Alkaloid Isolated from Ancistrocladus tectorius","The concise and efficient first total synthesis of 6-O-methyl anciscochine, employing a tandem C–C/C–N formation approach via a rhodium-catalyzed C–H activation/alkenylation/annulation strategy, is reported. This heterocycle was isolated from the liana Ancystrocladus tectorius and features a unique 3-hydroxymethylisoquinoline core that is found in a few other natural products and in some bioactive synthetic compounds. The synthesis, which was executed in four high-yielding steps and a global yield of 43%, involved the oximation of commercial 2,4-dimethoxyacetophenone under CeCl3·7H2O-promotion, followed by pivaloylation of the oxime. A one-pot pivaloxime-directed alkenyl­ation/annulation stage with methyl acrylate, furthered by a NaBH4/ CaCl2­-mediated reduction of the resulting isoquinoline 3-carboxylate ester completed the sequence.",10.1055/s-0039-1690701,2019-10-10,0.6430372463144028
Synthesis,Stereoselective Synthesis of Novel Isonucleoside Analogues of Purine with a Tetrahydropyran Ring,"New tetrahydropyran isonucleoside derivatives of purine, with cis or trans configuration, were stereoselectively synthesized in moderate yield by a convergent strategy based on Mitsunobu coupling. The key starting material was a bicyclic lactone.",10.1055/s-0029-1217142,2009-11-24,0.6430369728642977
Synlett,A Total Synthesis of (+)-Bacillamide B,A total synthesis of the halophile-derived natural product (+)-bacillamide B is described. The route relies upon a Hantzsch synthesis of ethyl (S)-2-acetoxyethylthiazole-4-carboxylate followed by a dipyridyl disulfide-mediated coupling between the corresponding carboxylic acid and tryptamine. This synthesis has unambiguously demonstrated that in contrast to the previous tentative stereochemical assignments the stereochemistry of the alcohol at C15 of the title compound has S-configuration.,10.1055/s-0029-1219153,2009-12-22,0.64299587104709
European Journal of Organic Chemistry,"Towards the Synthesis of the 4,19‐Diol Derivative of (–)‐Mycothiazole: Synthesis of a Potential Key Intermediate","Abstract The synthesis of a potential key intermediate for the synthesis of the 4,19‐diol derivative of (–)‐mycothiazole using convergent strategies is described in this paper. Several approaches have been tested, including cross metathesis and a Julia–Kocienski olefination. Finally, the formation of the 1,1‐dialkyl‐1,2‐ethanediol motif through C4–C5 bond construction was realized by nucleophilic addition of a vinyl iodide derivative to a keto ester after halogen/lithium exchange followed by reduction of the resulting hydroxy ester.",10.1002/ejoc.201100669,2011-08-30,0.6429924623352611
Organic Letters,"First Total Synthesis of Martinellic Acid, a Naturally Occurring Bradykinin Receptor Antagonist","[reaction: see text] The first total synthesis of martinellic acid, a naturally occurring bradykinin receptor antagonist, via a CuI-catalyzed coupling reaction of beta-amino ester 6 with 1,4-diiodobenzene and a guanylation reaction of secondary amine 3 under mild conditions as key steps, is described.",10.1021/ol016043h,2001-06-19,0.6429695572917015
Journal of Organic Chemistry,Protecting-Group-Free Total Synthesis of Aplykurodinone-1,"A concise, stereoselective, and protecting-group-free total synthesis of aplykurodinone-1 from Hajos-Parrish ketone was described. The synthetic approach features a sequence of aerobic allylic oxidation and elimination of alcohol 9. The key intermediate for this synthesis was formed by a stereoselective intramolecular radical cyclization.",10.1021/jo501684k,2014-11-10,0.642942312082709
Synlett,Improved Synthetic Route to C-Ring Ester-Functionalized Prodigiosenes,"An efficient, optimized, and scalable process for the synthesis of C-ring ester-functionalized prodigiosenes has been developed by (i) exploiting a silylative Mukaiyama aldol strategy for the condensation of alkyl 5-formyl-2,4-dimethylpyrrole-3-carboxylate and 4-methoxy-3-pyrrolin-2-one to form the corresponding ester-functionalized dipyrrinone analogues, and (ii) developing a facile synthesis of stable bromodipyrrin analogues for the use in formal Suzuki coupling reactions. The process was applied to the synthesis of three C-ring ester-functionalized prodigiosenes in multigram scales (up to 6.5 g prodigiosene free-base) with useful yields (35-56% overall yields over three steps starting from the 2-formyl pyrroles).",10.1055/s-0030-1258769,2010-09-30,0.6429414864157033
Journal of Organic Chemistry,De Novo Synthesis of Orthogonally-Protected C2-Fluoro Digitoxoses and Cymaroses: Development and Application for the Synthesis of Fluorinated Digoxin,"Inspired by Roush's pioneering work on rare sugars, we have developed a scalable, stereoselective, de novo synthesis of orthogonally protected C2-fluoro digitoxose and cymarose, utilizing Sharpless kinetic resolution and organocatalytic fluorination as key steps. The utility of this strategy is demonstrated by the synthesis of a fluorinated analogue of digoxin, which indicates the fluorine on the sugar ring may have a significant impact on biological activity.",10.1021/acs.joc.1c02592,2021-12-29,0.642936451166218
Journal of Organic Chemistry,"Total Synthesis of (±)-α-Isosparteine, (±)-β-Isosparteine, and (±)-Sparteine from a Common Tetraoxobispidine Intermediate","The three title alkaloids were separately prepared in stereocontrolled fashion from a common tetraoxobispidine precursor, 3,7-diallyl-2,4,6,8-tetraoxo-3,7-diazabicyclo[3.3.1]nonane (16). Bisimide 16 was generated from malonate via acid promoted cyclization of the Knoevenagel condensation adduct 1,1,3,3-propanetetracarboxamide. (+/-)-alpha-Isosparteine (dl-2) was elaborated from 16 in 28% overall yield by a two-directional synthetic sequence composed of four reactions: double addition of allylmagnesium bromide, ring-closing olefin metathesis (RCM), hydrogenation, and borane mediated reduction. (+/-)-beta-Isosparteine (dl-3) was targeted along similar lines by a strategic reversal in allylation and reduction operations on the core synthon. Thus, 16 was advanced to dl-3 in five steps and 12% overall yield by a reaction sequence commencing with sodium borohydride mediated reduction and followed by double Sakurai-type allylation of the resulting bishemiaminal. The synthesis of dl-3 was concluded by RCM and then global reduction (H2, Pd/C; LiAlH4). The final target, (+/-)-sparteine (dl-1), was secured in six steps and 11% overall yield from 16 by monoreduction and Sakurai allylation, followed by allyl Grignard addition and then RCM and global reduction as before. Reasons for the inherent C2-type regioselectivity of net double nucleophilic additions to tetraoxobispidines are discussed and enantioselective oxazaborolidine mediated reduction of the N,N'-dibenzyl congener of 16 is reported.",10.1021/jo8013512,2008-09-18,0.6429261825070194
Organic Letters,Total Synthesis of (±)-δ-Rubromycin,Transition-metal-catalyzed spiroketalization cyclization has been performed successfully and has led to the first total synthesis of (±)-δ-rubromycin with a longest linear sequence of 18 steps from commercially available guaiacol in a 2.7% overall yield.,10.1021/ol400864f,2013-05-01,0.6428853320496101
Journal of Organic Chemistry,Enantio- and Diastereocontrolled Total Synthesis of (+)-Boronolide,"An efficient stereoselective total synthesis of (+)-boronolide from valeraldehyde is described. The key steps include a Sharpless asymmetric hydroxylation, a chelation-controlled vinyl Grignard reaction followed by a Sharpless asymmetric epoxidation, hydrolytic kinetic resolution, and a ring-closing metathesis.",10.1021/jo0603781,2006-04-18,0.6428757900473355
Synlett,First Total Synthesis of (±)-Powelline,The first total synthesis of (±)-powelline is reported in 10% overall yield over eight steps using an intramolecular oxidative phenolic coupling reaction as the key reaction.,10.1055/s-0028-1083526,2008-10-01,0.6428716900862987
Synlett,An Improved Synthesis of Balsaminone A,"A short and efficient synthesis of balsaminone A, a dinaphthofuran-1,4-dione, is described. The eight-step synthesis features two alternate pathways including a base-induced coupling reaction of 4-methoxy-1-naphthol and 2,3-dichloro-1,4-naphthoquinone, as well as a light-mediated cyclization of 1,1'-binaphthoquinone to afford the dinaphthofurandione core. Subsequent ortho formylation yielded a known precursor to balsaminone A, affording the natural product in 20–27% yield. This represents a moderate increase from the previous synthesis of 7.4% yield.",10.1055/s-0037-1611975,2019-01-10,0.6428674031898346
European Journal of Organic Chemistry,"A Route to “all‐<i>cis</i>” 2‐Methyl‐6‐Substituted Piperidin‐3‐ol Alkaloids from <i>syn</i>‐(2<i>R</i>,1′<i>S</i>)‐2‐(1‐Dibenzylaminomethyl)epoxide: Rapid Total Synthesis of (+)‐Deoxocassine","Abstract A general strategy leading to the synthesis of two cis ‐2‐methyl‐6‐substituted piperidin‐3‐ols is described. syn ‐(2 R ,1′ S )‐2‐(1‐Dibenzylaminomethyl) epoxide ( 13 ) was used as common building block. The key step involved oxirane ring opening of 13 by the nucleophilic lithium aza‐enolate of hydrazones 12a and 12b . Subsequent hydrazone hydrolysis and intramolecular reductive amination afforded the alkaloid (+)‐deoxocassine and a new C‐6 ethyl analogue of this substance in good yields.",10.1002/ejoc.201101333,2011-11-17,0.6428558557983042
Journal of Organic Chemistry,An Efficient Stereoselective Synthesis of Stypodiol and Epistypodiol,"An efficient synthesis of stypodiol ( 1 ) and its epimer at C-14, epistypodiol ( 2 ), was accomplished starting from ( S )-(+)-carvone ( 7 ). The synthesis of both epimeric compounds proceeds through common intermediates using an IMDA reaction, a sonochemical Barbier reaction, and an acid-catalyzed quinol−tertiary alcohol cyclization as key synthetic steps.",10.1021/jo980311g,1998-07-01,0.6428527406979665
Synlett,Synthesis of C3-C12 Fragment of 24-Demethylbafilomycin C<sub>1</sub> via <i>anti</i>-Selective Aldol Condensation as the Key Stereocontrol Step,"An efficient synthesis of the C3-C12 aldehyde fragment of 24-demethylbafilomycin C<sub>1</sub> was accomplished for assembling the 16-membered plecomacrolide skeleton according to a 1,3-diene-ene ring-closing metathesis (RCM) strategy. A boron-mediated anti-selective aldol condensation of Abiko's chiral propionate was used to secure the C6 and C7 stereogenic centers while the C8 chirality was introduced from a chiral building block. The dithiane alkylation and the methyl ketone Horner-Wittig olefination using allyldiphenylphosphine oxide were employed for construction of the requisite (E)-1,3-diene subunit.",10.1055/s-2008-1072504,2008-03-17,0.6428465424607737
Journal of the American Chemical Society,"Total Synthesis of (+)-Calyculin A and (−)-Calyculin B:  Cyanotetraene Construction, Asymmetric Synthesis of the C(26−37) Oxazole, Fragment Assembly, and Final Elaboration","A convergent total synthesis leading to (+)-calyculin A and (−)-calyculin B ( 1 and 2 ), antipodes of the potent, highly selective and remarkably cell-permeable phosphatase inhibitors calyculins A and B, has been achieved. In the preceding paper we outlined the asymmetric synthesis of the C(9−25) spiroketal dipropionate subunit (+)- BC; herein we describe construction of the C(1−8) cyanotetraene, an asymmetric synthesis of the C(26−37) oxazole, fragment assembly and final elaboration to (+)- 1 and (−)- 2 . Highlights of the synthesis include: application of a one-pot three-component Suzuki reaction for the construction of phosphonate A, a bifunctional triene precursor of the light sensitive C(1−8) cyanotetraene subunit, an asymmetric synthesis of the C(26−32) oxazole (−)- D, exploiting the Silks−Odom 77 Se NMR protocol to assess enantiomeric purity, construction of the C(33−37) subtarget (−)- E in a highly stereocontrolled fashion via an acyliminium ion, and a concise, highly efficient sequence for fragment assembly and elaboration to (+)-calyculin A and (−)-calyculin B. The synthesis of (−)- 2 also confirms the structure of calyculin B, previously based only on spectral comparison with calyculin A.",10.1021/ja992135e,1999-10-30,0.6428411056538289
Organic Letters,Enantioselective Modular Synthesis of Cyclohexenones: Total Syntheses of (+)-Crypto- and (+)-Infectocaryone,"A modular synthesis of cyclohexenones is described and applied to the first enantioselective total syntheses of (+)-crypto- and (+)-infectocaryone. Key steps in the synthesis of cyclohexenones are an iridium-catalyzed allylic alkylation, nucleophilic allylation, and ring-closing metathesis. On the way to (+)-cryptocaryone, a catch and release strategy involving an iodolactonization/elimination and a regioselective C-acylation were used.",10.1021/ol101588j,2010-08-02,0.6428382376214665
Tetrahedron,A short and concise route to total synthesis of Dendrodolide L,,10.1016/j.tetlet.2017.04.097,2017-05-06,0.6428381687474928
Tetrahedron,"A novel synthetic route to enantiomers of ε-hydroxynorleucine and ε-chloronorleucine from L- and D,L-lysine",,10.1016/0040-4039(94)02278-j,1995-01-01,0.6428371241559401
Journal of Organic Chemistry,"Total Synthesis of the Natural Product Benzo[<i>j</i>]fluoranthene-4,9-diol: An Approach to the Synthesis of Oxygenated Benzo[<i>j</i>]fluoranthenes","A synthetic sequence to the benzo[j]fluoranthene nucleus is described. Crucial steps of the procedure include a Suzuki coupling between appropriately substituted 2-bromo-acenaphthylene-1-carbaldehydes and 2-formylbenzeneboronates followed by McMurry ring closure. The synthesis represents a new approach to the benzo[j]fluoranthene ring system and specifically provides a method for the rapid preparation of differently substituted derivatives. Following this strategy, the first total synthesis of the recently isolated natural product benzo[j]fluoranthene-4,9-diol was carried out.",10.1021/jo401887t,2013-10-01,0.6428353059810246
Journal of Organic Chemistry,Synthesis of the Spiroiminal Moiety and Approaches to the Synthesis of Marineosins A and B,"A short and efficient synthesis of model spiroiminals that have the same stereochemistry as marineosins A and B, but different conformations, was carried out in six or seven steps from 6-methyltetrahydropyran-2-one. These spiroiminals were also prepared biomimetically by reduction of an enol ether. A more highly substituted spiroiminal with the same stereochemistry and conformation as marineosin A was prepared in 11 steps from parasorbic acid. A macrocyclic pyrrole lactone was prepared stereospecifically in 10 steps. A five-step sequence converted the lactone to a late hemi-iminal intermediate that has resisted the methylation and spiroiminal formation that would lead to marineosin A.",10.1021/jo402178r,2013-11-07,0.6428261843426193
Synthesis,Expeditious Syntheses of Two Arylglycine Derivatives Corresponding to the Central Amino Acid of the Vancomycin Family of Antibiotics,"All articles of this category Two expeditious and efficient syntheses (in 7 and 4 steps, respectively) are described for the central amino acid part of the vancomycin family. The first method constitutes a concise asymmetric synthesis, starting from 4-hydroxyphenylacetic acid, of ( R )-(3,5-dihydroxy-4-methoxyphenyl)glycine derivatives using Evans’ asymmetric azidation methodology. In the second approach, an efficient synthesis of a protected 3,5-dichloro-4-methoxyphenylglycine derivative is described, starting from commercially available ( R )-4-hydroxyphenylglycine. These two syntheses are much shorter and operationally simpler than those previously described, and are currently employed in an effort towards the construction of the bicyclic system of vancomycin and ristocetin. vancomycin - antibiotic - arylglycine - asymmetric synthesis - amino acid",10.1055/s-1997-1234,1997-05-01,0.6428170934062685
Organic Process Research & Development,"Kilo-Scale-Enabled Route toward PF-07907063, a Type II Brain Penetrant cMET Inhibitor","New synthetic methodologies that access complex saturated building blocks enable the synthesis of drug molecules with unique properties. Here, we report collaborative efforts between Pfizer’s Medicinal Chemistry, Medicinal Chemistry Synthesis Development, and Pharmaceutical Sciences Small Molecule (PSSM) groups for the development of kilogram-scale-enabled synthesis of a type II brain penetrant cMET inhibitor, PF-07907063. The chemistry presented herein demonstrates the importance of implementing a green chemistry approach for developing and applying new transformations throughout the drug development pipeline. Specifically, synthetic planning rooted in the 12 Principles of Green Chemistry led to advancements in deoxygenative photoredox-nickel dual catalysis and cross-electrophile nickel catalysis. The final route significantly lowered the process mass intensity (PMI), increased the yield of the final API, and allowed for the purification of key intermediates through crystallization versus purging impurities via column chromatography, among other improvements.",10.1021/acs.oprd.4c00441,2025-04-07,0.642805334314086
Organic Letters,Total Synthesis of Oridamycins A and B,"The total synthesis of both oridamycin A and oridamycin B was accomplished starting from a common synthetic intermediate readily prepared from geranyl acetate. The sequence utilizes an oxidative radical cyclization to construct the trans-decalin ring system, setting three of four contiguous stereocenters in one operation. The carbazole nucleus was forged through a one-pot process entailing acid-promoted dehydration followed by 6π-electrocyclization/aromatization.",10.1021/acs.orglett.5b01629,2015-06-12,0.6427682574635795
Organic Process Research & Development,The Synthesis of a Selective PDE<sub>4</sub>/TNFα Inhibitor,"Two syntheses of cis -4-cyano-4-(1-cyclohexyl-3-ethyl-1H-indazol-6-yl)cyclohexanecarboxylic acid ( 1 ), a selective PDE 4 /TNFα inhibitor are described. The first synthesis relied on a solvolysis of a tertiary benzylic alcohol to the nitrile using TMSCN and on the epimerization of an ester to its thermodynamically favored position prior to its hydrolysis. It was demonstrated that the selectivity was controlled by the rate of hydrolysis of the two diastereomeric esters. The second synthesis proved to be more efficient and used a novel nucleophilic aromatic substitution of a fluoroindazole with the anion of a tertiary nitrile. Another key element of the route was a selective Pinner reaction of a secondary nitrile in the presence of a tertiary nitrile.",10.1021/op010223p,2001-10-03,0.6427517604711053
Organic Letters,Total Synthesis of the Alleged Structure of (+)-Fimbricalyxoid A,"An enantioselective total synthesis of the alleged structure of (+)-fimbricalyxoid A is reported. The synthetic strategy features a pyridine- N -oxidate-mediated S N 2′ reaction to introduce an oxygen functionality at position C3 of the A-ring and a sequential three-step process via the cleavage of the C–O bonds and hemiketalization to form the 3,20-oxybridge. With this strategy, the target molecule was synthesized in 19% overall yield and 12 steps from our previously synthesized cis -fused octahydrophenanthrene (+)- 6 .",10.1021/acs.orglett.2c01076,2022-05-06,0.6427503998702224
Organic Letters,Synthesis of the Tagetitoxin Core via Photo-Stevens Rearrangement,"The core structure of the RNA polymerase inhibitor tagetitoxin has been synthesized by one-carbon ring expansion of bridged bicyclic monothioacetals. The key steps are intramolecular ylide formation by reaction between the sulfur atom and a pendant diazoester, followed by an efficient photochemical 1,2-rearrangement to give the desired 9-oxa-3-thiabicyclo[3.3.1]nonane ring system.",10.1021/ol802297h,2008-10-31,0.6427497254040974
Tetrahedron,A practical synthesis of betulinic acid,,10.1016/j.tetlet.2006.10.004,2006-10-21,0.6427176402811347
Journal of Organic Chemistry,Total Synthesis of Cryptophycins via a Chemoenzymatic Approach,"A highly convergent synthesis of cryptophycins in their enantiomerically-pure forms was achieved. Our strategy consists of the synthesis of the two units 3 and 4 and linking them together to form the macrocyclic ring. The upper unit 3 was prepared from 10 in four steps, and the lower unit 4 was prepared from 20 in three steps. Enantioselective biocatalytic methodology was used to prepare the requisite chiral building blocks, (R)-11 and (R)-19. The stereochemical versatility of this synthetic approach is demonstrated by the synthesis of cryptophycin A and the four diastereomers of cryptophycin C.",10.1021/jo960972i,1996-01-01,0.6427169459171348
Tetrahedron,A general synthetic route towards bastadins. Part 1: Synthesis of the eastern part of bastadins 4–16,,10.1016/s0040-4039(99)01429-x,1999-09-01,0.6427143816999026
Synlett,Total Synthesis of Endolides A and B,"The total synthesis of endolides A and B has been achieved in a concise, highly stereoselective fashion (12 steps, 16.2% and 16.0% overall yields, respectively). Key features of the route include a modified Negishi coupling between 3-bromofuran and an organozinc reagent derived from an iodoalanine derivative for the synthesis of 3-(3-furyl)-alanine derivative, and a judicious choice of reaction conditions to surmount the conformational constraints placed by converting a linear peptide into the corresponding macrocycle.",10.1055/s-0037-1610736,2019-11-14,0.6427086555082514
Organic Letters,"Facile Synthesis of a Benzindenoazepine Alkaloid, Bulgaramine, via Samarium Diiodide Promoted Ring Expansion of an α-Aminocarbonyl Compound","A novel synthetic path to a benzindenoazepine alkaloid was established by employing a samarium diiodide promoted ring expansion reaction of an alpha-aminocarbonyl compound as a key reaction, in which a regioselective carbon-nitrogen bond cleavage followed by ring-closing reactions occurred to give the basic ring skeleton of the target compound. Bulgaramine was synthesized from the known tetrahydroisoquinoline derivative in 5 steps in 50% overall yield.",10.1021/ol9004239,2009-03-18,0.6427076964280295
European Journal of Organic Chemistry,"Asymmetric Synthesis of Arylglycines and Their Use as Chiral Templates for the Stereocontrolled Synthesis of 7,8-Disubstituted 3-Aryl-1,2,3,4-tetrahydroisoquinolin-4-ols","A synthetic technique for the asymmetric synthesis of arylglycines has been optimized, reaching the target amino acids in only four steps with good yields and with enantiomeric excesses higher than 99%. The key step consisted of a stereocontrolled electrophilic amination reaction of (S,S)-(+)-pseudoephedrine-based arylacetamide enolates with di-tert-butylazodicarboxylate. The arylglycines thus obtained turned out to be excellent chiral templates for the production of chiral, nonracemic 7,8-disubstituted 3-aryl-1,2,3,4-tetrahydroisoquinolines, through use of a synthetic sequence involving: (1) reduction of the arylglycines to the parent arylglycinols, (2) N-benzylation with appropriately substituted aromatic aldehydes and (3) Swern oxidation followed by acid-catalysed cyclization of the obtained α-amino aldehydes.",10.1002/1099-0690(200111)2001:22<4343::aid-ejoc4343>3.0.co;2-d,2001-11-01,0.6427063697523626
Synthesis,Synthesis of Acenaphthene-1-carboxylic Acid Using Lithiated Tris(methylthio)methane to Carboxylate 1-Bromoacenaphthene,"All articles of this category A new synthesis of acenaphthene-1-carboxylic acid ( 4 ) in 3 steps and 78% overall yield from 1-bromoacenaphthene ( 1 ) is described. In the key step, lithiated tris(methylthio)methane is reacted with 1-bromoacenaphthene to give 1-[tris(methylthio)methyl]acenaphthene ( 2 ). Methanolysis of 2 gives racemic methyl acenaphthene-1-carboxylate 3 , which is resolved by chiral chromatography. The usefulness of tris(methylthio)methyllithium as a carboxyl carbanion equivalent is illustrated by the conversion of three other bromides to the corresponding methoxycarbonyl derivatives.",10.1055/s-1990-26925,1990-01-01,0.6426902119185015
Journal of Organic Chemistry,First Total Synthesis of 1-<i>O</i>-β-<scp>d</scp>-Glucopyranosyl-5-deoxyadenophorine and Its Aglycon Congener:  Determination of the Absolute Configuration,"The first total synthesis of the potent glycosidase inhibitors 1-O-beta-D-glucopyranosyl-5-deoxyadenophorine and its aglycon congener is described in respectively 13 steps (9% overall yield) and 9 steps (29% overall yield) from (R)-Garner aldehyde. The synthesis takes advantage of several key reactions including a diastereoselective allylation of a chiral imine, a stereoselective epoxidation, and a glycoside coupling. In addition this study established unambiguously the absolute configuration of the natural products.",10.1021/jo035522m,2004-02-06,0.642681145164583
Journal of Organic Chemistry,Convergent Total Synthesis of Lamellarins and Their Congeners,"A convergent total synthesis of lamellarins S and Z is described. The synthesis features a halogen dance of an easily accessible α,β-dibromopyrrole promoted by an ester moiety. The resultant β,β'-dibromopyrrole undergoes a ligand-controlled Suzuki-Miyaura coupling to provide a range of diarylated pyrrole derivatives. The established synthetic method was also applicable to the synthesis of ningalin B and lukianols A and B.",10.1021/acs.joc.0c00998,2020-05-28,0.6426693637604249
Tetrahedron,New and efficient synthetic routes to 1-deoxy-D-xylulose,,10.1016/s0040-4039(98)00310-4,1998-04-01,0.6426483066312295
Organic Process Research & Development,Novel Synthetic Route of a Pivotal Intermediate for the Synthesis of 1β-Methyl Carbapenem Antibiotics,"A novel synthetic method using an original and practical procedure for the preparation of the N -PNZ protected 2-aminomethylpyrrolidin-4-ylthio-containing side chain of doripenem hydrate ( S-4661 ), a new parenteral 1β-methylcarbapenem antibiotic, is described. trans -4-Hydroxy- l -proline was converted through an efficient process to (2 S,4 S )-4-acetylthio-2-( N -sulfamoyl-4-nitro-benzyloxycarbonyl - aminomethyl)-1-(4-nitrobenzyloxycarbonyl) pyrrolidine with 60−70% overall yield via a two-step sequence. This procedure requires no chromatographic purifications, no cryogenic temperatures, no haloalkane solvent, and shorter operating times and avoids the side reaction brought by acid hydrolysis. Furthermore, the product was obtained as a crystal rather than an oil, which made it to be an advantage for quantization in the pilot-scale manufacture. Several kilograms of the side chain were prepared by using this method.",10.1021/op0600714,2006-06-29,0.6426447575013994
Angewandte Chemie International Edition,Total Synthesis of (−)‐Vindorosine,"Outlined herein is a novel and scalable synthesis of (-)-vindorosine based on two key transformations. A highly diastereoselective vinylogous Mannich addition of dioxinone-derived lithium dienolates with indolyl N-tert-butanesulfinyl imines has been developed. In addition, an intramolecular Heathcock/aza-Prins cyclization was introduced to construct both the C, and the highly substituted E rings for the synthesis of (-)-vindorosine and related alkaloids.",10.1002/anie.201707249,2017-08-06,0.6426387992174724
Organic Letters,Synthetic Studies on Norrisolide:  Enantioselective Synthesis of the Norrisane Side Chain,"Norrisolide ( 1 ) belongs to a family of marine diterpenes that are characterized by the assembly of a bicyclic core with a unique and highly oxygenated side chain (norrisane side chain). As a prelude to the synthesis of 1, we present herein a short, efficient, and enantioselective synthesis of the norrisane side chain 4 . The synthetic route toward 4 departs from d -mannose and is short (11 steps), efficient, and enantioselective.",10.1021/ol9909785,1999-09-23,0.6426352620877377
Tetrahedron,Synthesis of a constrained enkephalin analog to illustrate a novel route to the piperazinone ring structure,,10.1016/s0040-4039(97)10530-5,1998-01-01,0.6426047004138306
Tetrahedron,"An efficient total synthesis of K-13, a non-competitive inhibitor of ACE I",,10.1016/s0040-4039(00)00695-x,2000-06-01,0.6425564522999948
Angewandte Chemie International Edition,A Concise Asymmetric Synthesis of the Marine Hepatotoxin 7‐Epicylindrospermopsin,"Born from a simple amino acid …︁ the potent hepatotoxic cyanobacterial alkaloid 7-epicylindrospermopsin (see picture) has been synthesized through a concise asymmetric eighteen-step route. An intramolecular 1,3-dipolar cycloaddition and a nitroaldol reaction are key steps in the construction of the natural product from a precursor with a single stereogenic center.",10.1002/anie.200454208,2004-05-06,0.6425432613381146
Organic Letters,Novel Synthesis of the Glycosidase Inhibitor Deoxymannojirimycin and of a Synthetic Precursor <scp>d</scp>-<i>l</i><i>yxo</i>-Hexos-5-ulose,"[reaction: see text]. The synthesis of D-lyxo-hexos-5-ulose (5-ketomannose, 1,5-dicarbonyl sugar), a synthetic precursor to the glycoprocessing inhibitor deoxymannojirimycin, was carried out by an in situ epoxidation and hydrolysis of a trimethylsilyl-protected 6-deoxyhex-5-enopyranoside followed by facile removal of the protecting groups. A novel nine-step synthesis of deoxymannojirimycin has also been achieved from methyl alpha-D-mannopyranoside; this involved methanolysis of epoxides derived from an acetylated 1-azido-6-deoxyhex-5-enopyranoside followed by deprotection and catalytic hydrogenation.",10.1021/ol016596s,2001-09-27,0.6425395023360192
Synlett,Total Synthesis of 1-Oxomiltirone and Arucadiol,A practical and efficient approach for the total synthesis of arucadiol and 1-oxomiltirone is reported. The key step which involves an intramolecular [4+2] cycloaddition catalyzed by gold(III) bromide or copper(II) triflate leads to the formation of 6-6-6-fused aromatic abietane core.,10.1055/s-0039-1690743,2019-11-05,0.6425378725654094
Tetrahedron,A concise new route to 3-deoxy-d-manno-2-octulosonic acid (KDO) from D-arabinose and 2-acetylthiazole,,10.1016/s0040-4039(00)97663-9,1990-01-01,0.6425301323093818
Organic Letters,Asymmetric Synthesis of <i>C</i><sub>2</sub>-Symmetric Vicinal Diamines via Reductive Dimerization of <i>N-</i>Acylpyridinium and Related Salts,A new route to C2-symmetric diamines via an asymmetric reductive dimerization of 1-acylpyridinium salts and their benzo derivatives is described. This method is practical as the starting heterocycles and chiral auxiliaries are readily available. The titanium reducing agent is inexpensive and easy to prepare. Several novel enantiopure C2-symmetric diamine derivatives were synthesized using this method.,10.1021/ol702595d,2007-12-20,0.6425194798581356
European Journal of Organic Chemistry,"Total Synthesis of Dictyodendrins B and E, and Formal Synthesis of Dictyodendrin C","Abstract A full account of the concise total syntheses of dictyodendrins B and E, and the formal synthesis of dictyodendrin C are described. A palladium‐catalysed Larock indole synthesis was used to form the highly substituted indole core, and a palladium‐mediated one‐pot consecutive Buchwald–Hartwig amination/C–H activation reaction was used to construct the key pyrrolo[2,3‐ c ]carbazole core. Unsuccessful synthetic strategies are also discussed.",10.1002/ejoc.201402672,2014-07-28,0.642516427183674
Organic Letters,Scalable Synthesis of a Key Intermediate for the Production of Pleuromutilin-Based Antibiotics,"An improved synthesis of an eneimide, which is a useful precursor to pleuromutilin-based antibiotics, is reported. This synthesis proceeds in six steps and 17% overall yield (27% based on recovery of a key hydrindenone intermediate) and requires two fewer chromatography steps and five fewer days of reaction time than the previously reported route. The use of expensive, acutely toxic, and precious metal reagents or catalysts has been minimized.",10.1021/acs.orglett.7b02476,2017-08-31,0.6425073085684803
Angewandte Chemie International Edition,Total Synthesis of Leucascandrolide A,"A compound that could never be isolated again despite intensive efforts after it was first found in the sponge Leucascandra caveolata in 1996 is leucascandrolide A (1). An enantioselective, convergent total synthesis of this polyoxygenated marine macrolide proceeds in 23 steps and 2 % overall yield. The strategy relies on the application of modern asymmetric reactions for enantio- and diastereoselective transformations.",10.1002/1521-3773(20021104)41:21<4098::aid-anie4098>3.0.co;2-p,2002-10-31,0.6425070815442608
Angewandte Chemie International Edition,Total Synthesis and Stereochemical Reassignment of (+)‐Neopeltolide,"Take a closer look! The first enantioselective total synthesis, stereochemical reassignment, and absolute configuration of the metabolite neopeltolide is described (see picture). Synthetic highlights of this route include a modified Evans–Tishchenko reduction to introduce the C11 stereocenter, [4+2] annulation to construct the pyran system, and a Still–Gennari olefination to install the oxazole side chain.",10.1002/anie.200704122,2007-11-16,0.6424978602493412
Synthesis,Asymmetric Synthesis of the Four Stereoisomers of 4-Hydroxypipecolic Acid,"All articles of this category The asymmetric synthesis of all four stereoisomers of 4-hydroxypipecolic acid ( 1 ) from the polyfunctionalized chiral building blocks δ-amino β-keto esters ( S S , R )-(+)- 5 or ( R s , S )-(-)- 5 is described. Key steps in the synthesis are the stereoselective reductions of b-phenylpiperidine-2,4-dione ( 6 ) and N -sulfinyl δ-amino β-keto esters 5 to cis -4-hydroxy 2-piperidinone 7 and syn -δ-amino β -hydroxy ester 9 , respectively. The only protecting/deprotecting group chemistry required is related to the oxidation step. stereoselective reductions - hydrides - cyclization - asymmetric synthesis - piperidines",10.1055/s-2000-8710,2000-01-01,0.6424975910853822
Tetrahedron,"Synthesis of (E)-2-(4,7-dichloroquinolin-2-yl)-3-dimethylamino-2-propene-1-al and its use as a synthetic intermediate",,10.1016/0040-4039(94)02248-a,1995-01-01,0.6424757212215233
Synthesis,"A Selective and Efficient Synthesis of Quisqualamine, a Novel GABA-Related Depressant Amino Acid",,10.1055/s-1982-29944,1982-01-01,0.642458603557583
Journal of Organic Chemistry,Synthesis of Diazatricyclic Core of Madangamines from <i>cis</i>-Perhydroisoquinolines,"Synthesis of the tricyclic core of madangamine alkaloids has been achieved in a 10-step sequence starting from a 4-(aminomethyl)anisole derivative. A Birch reduction and acylation with cyanoacetic acid followed by an intramolecular Michael process renders a polyfunctionalized cis-perhydroisoquinoline. A diastereoselective allylation and reduction of amide, nitrile, and ketone groups leads to a bicyclic alcohol, which undergoes aminocyclization through the nosyl derivative to the diazatricyclic ring.",10.1021/jo702340w,2007-12-21,0.6424447856857222
Organic Process Research & Development,Development of an Optimized Synthetic Process for Onradivir Featuring a “One-Pot” Miyaura–Suzuki Coupling Reaction,"Influenza A virus (IAV) is a highly contagious pathogen responsible for significant global morbidity and mortality, with an estimated 1 billion infections annually. Onradivir, a next-generation PB2 inhibitor derived from Pimodivir, shows superior activity against drug-resistant IAV variants but faces manufacturing challenges. We report a scalable 7-step synthesis featuring two key innovations: (1) a silver-catalyzed radical cyclopropylation (89.5% conversion) replacing hazardous Grignard reagents; (2) a streamlined one-pot Miyaura–Suzuki coupling achieving 66% yield for intermediate 8 . The route eliminates column chromatography through strategic recrystallizations, reduces Pd catalyst loading, and employs cost-effective ethyl acetate solvent. Process optimizations at 15 g scale demonstrate a consistent 5.8% yield for the API (representing a 7-fold improvement over the original method), with all intermediates either crystallized or telescoped to minimize purification losses. The developed methodology facilitates the commercial development of Onradivir and provides a general platform for the synthesis of structurally complex PB2 inhibitors.",10.1021/acs.oprd.5c00175,2025-10-16,0.6424396410777558
Journal of Organic Chemistry,Synthesis of Novel Retinoid X Receptor-Selective Retinoids,"Retinoids 1-5 have been identified as potent RXR agonists for evaluation in the treatment of non-insulin-dependent (type II) diabetes mellitus (NIDDM). Highly convergent syntheses of 1-5 have been developed. The core tetrahydronaphthalene 7, employed in the synthesis of 1 and 2, was prepared in 98% yield using an AlCl(3)-catalyzed (0.03 equiv) Friedel-Crafts alkylation of toluene with 2,5-dichloro-2,5-dimethylhexane 6. A nitromethane-mediated Fridel-Crafts acylation of 7 with chloromethylnicotinate 9 was developed to prepare ketone 10 in 68% yield. Chelate-controlled addition of MeMgCl to 10 followed by dehydration afforded olefin 11 in 65% yield. Cyclopropanation of 11 with trimethylsulfoxonium ylide, followed by saponification, completed a five-step synthesis of 1 in 33% yield. FeCl(3)-catalyzed (0.05 equiv) Friedel-Crafts acylation of 7 with chloromethylterephthalate 14 afforded ketone 15 in 81% yield. Saponification of 15 and reaction with 50% aqueous NH(2)OH in AcOH afforded a 9:1 mixture of cis and trans oximes, from which the desired cis-oxime 2 was isolated in 43% yield. The core bromo-dihydronaphthalene 29 required for the synthesis of 3-5 was prepared by a Shapiro reaction. Transmetalation of 29 and reaction with Weinreb amides 30b or 36 afforded ketones 32 and 37, which were converted into 3-5 using chemistry comparable to the tetrahydronaphthylene series. Suzuki coupling of boronic acids 41 and 42 with vinyl triflate 43 provided an alternative approach to the synthesis of this class of compounds.",10.1021/jo0103064,2001-08-01,0.6424251729981239
Tetrahedron,A concise and scalable synthesis of a novel l-allo-enduracididine derivative,,10.1016/j.tetlet.2020.152148,2020-06-16,0.6424182726007633
Synlett,Stereoselective Synthesis of Polyketide Segments of Nemamide A and Euglenatides D–E,"Abstract A convergent strategy for the stereoselective synthesis of polyketide segments of hybrid natural products nemamide A and euglenatides D–E has been developed for the first time. The salient features of this gram-scale synthesis include Trost–Rychnovsky alkyne rearrangement, HWE olefination, regioselective epoxide ring opening, Prins–Ritter cyclization, and subsequent reductive cleavage of the substituted THP ring. The optimized route is modular and could be tunable to access the other polyketide counterparts of these families of metabolites.",10.1055/a-2361-3510,2024-07-07,0.6424124363523367
Angewandte Chemie International Edition,Enantioselective Total Synthesis of (−)‐Stenine,"In control: (−)-Stenine has been synthesized in 14 steps from commercially available compounds with an overall yield of 5.9 % by using a method that is based on double Michael addition. In the key step, the stereogenic centers that are required for (−)-stenine are generated in a highly stereocontrolled, asymmetric, one-pot cyclization to give a densely substituted cyclohexane core.",10.1002/anie.201106587,2011-12-16,0.6423699860942332
Synthesis,A Novel Synthesis of Allophenylnorstatine from (R)-Aspartic Acid,,10.1055/s-1999-3495,1999-06-01,0.642338756481815
Tetrahedron,"Synthesis of 2,4,5-triaminocyclohexanecarboxylic acid as a novel 2-deoxystreptamine mimic",,10.1016/j.tetlet.2010.01.111,2010-02-03,0.642338756481815
Tetrahedron,Synthesis of a novel dioxan sialic acid analog,,10.1016/j.tetlet.2004.03.135,2004-04-21,0.642338756481815
Tetrahedron,A novel synthesis of cyclobutenecarboxylic acid from α-acetylcyclopentanone,,10.1016/s0040-4039(01)87384-6,1973-01-01,0.642338756481815
Organic Letters,Enantioselective Total Synthesis of Aspidophytine,"[structure: see text] An enantioselective total synthesis of aspidophytine is described. The indole fragment bearing a cis-alkene substituent was efficiently prepared through radical cyclization of a 2-alkenylphenylisocyanide followed by Sonogashira coupling of the generated 2-iodoindole derivative with a functionalized acetylene unit. After formation of the 11-membered cyclic amine, the aspidosperma skeleton and lactone ring were constructed to complete the total synthesis.",10.1021/ol034445e,2003-04-26,0.6422873840656447
Journal of Organic Chemistry,Total Synthesis of Aspidofractinine Alkaloid Paucidirinine,"The first total synthesis of paucidirinine ( 1d ), a highly congested aspidofractinine alkaloid containing a special contracted five-membered lactam ring, was achieved in 10 steps with 8% overall yield from commercially available materials. Several key maneuvers, including tandem enamination/[4 + 2] cycloaddition reaction and SmI 2 -promoted radical cyclization, were featured in this potentially scalable strategy.",10.1021/acs.joc.8b03023,2018-12-18,0.6422805725215537
Organic Letters,Synthesis of the <i>Mycobacterium tuberculosis</i> Canetti Lipooligosaccharide II Nonasaccharide,"A route for preparing lipooligosaccharide (LOS) glycans from Mycobacterium tuberculosis Canetti was developed and applied to the most complex of these structures, LOS II. The synthesis of the target nonasaccharide was achieved via a convergent [3+3+3] approach. Key features of the strategy include the stereoselective synthesis of an asymmetrically substituted trehalose moiety from two protected glucose residues and several chemoselective glycosylations involving thioglycoside donors.",10.1021/acs.orglett.2c02518,2022-08-25,0.6422558449259848
Organic Letters,Asymmetric Synthesis of <scp>l</scp>-Carbidopa Based on a Highly Enantioselective α-Amination,"A stereoselective synthesis of L-carbidopa in seven steps and 50% overall yield from commercial compounds is described. The key step involves a highly enantioselective α-amination reaction of an acyclic β-ketoester with di-tert-butyl azodicarboxylate induced by europium and (R,R)-diphenyl-pybox.",10.1021/ol400136y,2013-03-11,0.6422510571156852
Organic Letters,Matteson Homologation-Based Total Synthesis of Meliponamycin A,"The first total synthesis of meliponamycin A, an antimicrobial cyclodepsipeptide isolated from Streptomyces, is reported. Two key building blocks, the substituted tetrahydropyranyl side chain and an azido analogue of protected β-hydroxyleucine, were constructed via iterative Matteson homologations. A fragment coupling of a tetrapeptide, a depsidipeptide building block, macrocyclization, Staudinger reduction, and N -acylation are further steps in the synthesis.",10.1021/acs.orglett.3c03766,2023-12-26,0.6422408958327143
Synthesis,"Synthesis of New Trifluoromethylated Furans, Dihydrofurans and Butenolides Starting from γ-Ketothioesters and Diisopropylamine",International audience,10.1055/s-2006-926352,2006-01-01,0.6422363268359794
Angewandte Chemie International Edition,"Synthesis of the DFGH ring system of Type B Physalins: Highly Oxygenated, Cage‐Shaped Molecules","Let the dominos fall: Synthesis of the complex DFGH ring system of the title compounds has been accomplished. The approach features simple treatment of the key intermediate with a Brønsted base to afford the tetracyclic cage-shaped target in one pot through a four-step domino transformation (see scheme; Mc = monochloromesylate, MOM = methoxymethyl).",10.1002/anie.200900634,2009-04-19,0.6422291935250414
Journal of Organic Chemistry,"Asymmetric Synthesis of CIDD-0072424 via an Enantioselective Nitro-Mannich Reaction: A Central Nervous System Penetrant, Selective Small Molecule Inhibitor of Protein Kinase C Epsilon","CIDD-0072424 is a novel small molecule developed in silico with remarkable activity for the inhibition of protein kinase C (PKC)-epsilon to treat alcohol use disorder. We developed a concise synthesis of ( S )- 2 that is highly enantioselective, scalable, and amenable for 3-point structure–activity relationship (SAR) studies for compound optimization. The highly enantioselective nitro-Mannich reaction was achieved through a dual-reagent catalysis system. The overall utility and the efficiency of the enantioselective route provided a scalable synthesis of both PKCε inhibitors 1 and 2 .",10.1021/acs.joc.3c02917,2024-03-15,0.6422177065247558
Organic Process Research & Development,"A Practical Synthesis of the PDE4 Inhibitor, SB-207499, from a Cyclohexanone Precursor","The synthesis of SB-207499 is described. Investigation and development of new strategies for the homologation of ketone, 4-cyano-4-[3-(cyclopentyloxy)-4-(methoxyphenyl)]-cyclohexan-1-one 2 are described which produce SB-207499. Our ultimate route of synthesis to SB-207499 is robust and operationally simple and produces the final drug substance in good yield and purity.",10.1021/op025584z,2002-10-30,0.6422068159660123
Tetrahedron,Norbornyl route to polyoxygenated cyclohexanes. An approach to pancratistatin and narciclasine alkaloids,,10.1016/s0040-4039(98)00470-5,1998-05-01,0.6421914045149174
Angewandte Chemie International Edition,Total Synthesis Guided Structure Elucidation of (+)‐Psychotetramine,Solving the puzzles: Total synthesis played a key role in the elucidation of the stereochemistry and verification of the constitution of the complex polymeric natural product psychotetramine. The route features three powerful assembly processes that enabled four rounds of total synthesis-guided structure determination. The pursuit of this alkaloid also led to an improved procedure for indole–aniline coupling and a highly efficient enantioselective synthesis of psychotrimine.,10.1002/anie.201008048,2011-02-17,0.6421701023619635
Journal of Organic Chemistry,"Enantioselective Synthesis of (2<i>S</i>,3<i>R</i>)-3-Hydroxy-3-methylproline, A Novel Amino Acid Found in Polyoxypeptins","The enantioselective synthesis of (2S,3R)-3-hydroxy-3-methylproline (3) was achieved by the Sharpless AD, regioselective opening of cyclic sulfate by NaN(3) and intramolecular ring-closing reaction. The reported route has the advantage of a high overall yield and good enantiomeric purity, as well as starting from readily available chemical substrates and inexpensive reagents.",10.1021/jo016227+,2002-01-09,0.6421392087203248
European Journal of Organic Chemistry,Stereoselective Synthesis of a Bicyclic Norsesquiterpene Backbone – A Possible Route to Nardosinane Derivatives,"Abstract We have developed an efficient diastereoselective synthetic route towards a nardosinane sesquiterpene scaffold. The strategy used a key bicyclic diene intermediate 11a , and allowed access to valuable polyoxygenated sesquiterpenes 21 and 22 , which may be regarded as analogues of the natural sesquiterpenes laevinol B and fulvol acetate, respectively.",10.1002/ejoc.201301087,2013-09-17,0.6421289476290062
Organic Process Research & Development,"Correction to “An Expedient Approach for the Synthesis of TAM and MET Receptor Kinase Inhibitor’s Core ( <i>R</i> )-2-((4-(4-Amino-2-fluorophenoxy)-1-(4-methoxybenzyl)-1 <i>H</i> -pyrazolo[3,4- <i>b</i> ]pyridin-3-yl)amino)propan-1-ol”",,10.1021/acs.oprd.5c00405,2025-11-26,0.6421179692279103
Journal of Organic Chemistry,"Aryl Amidation Routes to Dihydropyrrolo[3,2-<i>e</i>]indoles and Pyrrolo[3,2-<i>f</i>]tetrahydroquinolines:  Total Synthesis of the (±)-CC-1065 CPI Subunit","CC-1065 and the related duocarmycins are members of a structurally unique family of naturally occurring molecules and remain some of the most rigorously studied antitumor compounds to date. Herein we describe a total synthesis of the (+/-)-CC-1065 CPI subunit in an overall yield of 9.3% from commercially available 5-fluoro-2-nitrophenol. The key steps of this synthesis are a Diels-Alder reaction of an o-benzoxy-monoimine quinoid and an intramolecular aryl triflate amidation, which formed the pyrrolo[3,2-f]tetrahydroquinoline intermediate en route to CPI.",10.1021/jo062064j,2006-12-15,0.6421177224539331
Synlett,A New Synthetic Route to Indoloquinones: Formal Synthesis of Ellipticine,The anionic [4+2] cycloaddition of furoindolones with arynes and quinol ethers is introduced as an efficient strategy for the synthesis of indoloquinones. The utility of the strategy is exemplified by a very short synthesis of elipticine.,10.1055/s-2005-864826,2005-03-23,0.642103453467929
Tetrahedron,"Predisposition in synthesis: efficient routes to (±)-untenone A and (±)-manzamenones A, C and F",,10.1016/s0040-4039(00)00399-3,2000-04-01,0.6420964857629371
Journal of Organic Chemistry,Total Synthesis of (+)-Brefeldin A,The total synthesis of (+)-brefeldin A has been accomplished via 15 linear steps in a 7.9% overall yield from the known Weinreb amide 6. The key parts of this approach include the stereoselective construction of the cis-disubstituted hydroxycyclopentane skeleton and the direct introduction of the C1-C3 acrylate moiety using a new variant of a trans-vinylogous acyl anion equivalent.,10.1021/jo0110855,2002-05-16,0.6420955376568973
Angewandte Chemie International Edition,Bioinspired Total Synthesis of <i>Cephalotaxus</i> Diterpenoids and Their Structural Analogues,"Abstract Herein, we present a unified chemical synthesis of three subgroups of cephalotaxus diterpenoids. Key to the success lies in adopting a synthetic strategy that is inspired by biosynthesis but is opposite in nature. By employing selective one‐carbon introduction and ring expansion operations, we have successfully converted cephalotane‐type C 18 dinorditerpenoids (using cephanolide B as a starting material) into troponoid‐type C 19 norditerpenoids and intact cephalotane‐type C 20 diterpenoids. This synthetic approach has enabled us to synthesize cephinoid H, 13‐ oxo ‐cephinoid H, 7‐ oxo ‐cephinoid H, fortalpinoid C, 7‐ epi ‐fortalpinoid C, cephanolide E, and 13‐ epi ‐cephanolide E. Furthermore, through the development of an intermolecular asymmetric Michael reaction between β ‐oxo esters and β ‐substituted enones, we have achieved the enantioselective synthesis of advanced intermediates within our synthetic sequence, thus formally realizing the asymmetric total synthesis of the cephalotaxus diterpenoids family.",10.1002/anie.202402931,2024-03-25,0.6420897713155442
Synlett,Rapid Access to the Potential Intermediate for the Synthesis of Halenaquinol and Halenaquinone,"All articles of this category The short step access to the possible intermediate for the synthesis of halenaquinone and halenaquinol of the dihydrofuranfused tetracyclic ring core ( 7 ) using the intramolecular [4 + 2] cycloaddition reaction of the o -quinodimethane, generated from 6 , as the key step is described. halenaquinone - halenaquinol - o -quinodimethane - benzocyclobutene",10.1055/s-2001-15165,2001-01-01,0.6420836896124477
Organic Letters,"Efficient, Stereodivergent Access to 3-Piperidinols by Traceless P(OEt)<sub>3</sub> Cyclodehydration","A stereodivergent and highly diastereoselective (dr up to >19:1 for both isomers), step economic (5-6 steps), and scalable synthesis (up to 14 g) of cis- and trans-2-substituted 3-piperidinols, the core motif of numerous bioactive compounds, providing efficient access to the NK-1 inhibitor L-733,060 is presented. Additionally, a ""traceless"" (referring to the simplified byproduct separation) cyclodehydration realizing simple P(OEt)3 as a substitute for PPh3 is developed.",10.1021/ol4026588,2013-10-03,0.6420802988186227
Journal of Organic Chemistry,"A Simple, Short, and Flexible Synthesis of Viridiofungin Derivatives","Described herein is a simple, flexible, and efficient synthesis of the skeleton of the viridiofungins, a family of microbial secondary metabolites. The synthesis utilizes an asymmetric aldol reaction of a chiral oxazolidinone, a diastereoselective alkylation of a chiral 1,3-dioxolan-2-one, and a geometrically selective alkene cross-metathesis reaction as the key C-C bond-forming steps.",10.1021/jo060931e,2006-06-30,0.642078567024983
Synlett,A Short and Scalable Total Synthesis of (±)-β-Eudesmol,"Abstract A concise, protecting group-free approach has been developed for the total synthesis of (±)-β-eudesmol (1), completed in four steps with an overall yield of 24%. This synthesis features a copper-catalyzed Michael addition followed by an in situ aldol reaction, and a one-step Fe(III)/Et3SiH-mediated radical cyclization–oxidation sequence that efficiently constructs the eudesmane skeleton. With its operational simplicity and scalability, this strategy provides a valuable platform for the synthesis of structurally related sesquiterpenoid architectures, paving the way for further biological and structural investigations.",10.1055/a-2618-1156,2025-07-31,0.6420748373966148
Organic Process Research & Development,Development of a Safe Process for Manufacturing of the Potent Anticancer Agent Melflufen Hydrochloride,Melflufen is a novel cytostatic currently in phase III clinical trials for treatment of multiple myeloma. Development of a process suitable for production is described. The two key features of the novel method are late introduction of the alkylating pharmacophore and an improved method for formation of the bis-chloroethyl group.,10.1021/acs.oprd.9b00116,2019-05-13,0.6420732994058054
Organic Letters,"Total Synthesis of GEX1Q1, Assignment of C-5 Stereoconfiguration and Evaluation of Spliceosome Inhibitory Activity",An enantioselective total synthesis of GEX1Q1 has been accomplished in a convergent manner. The C-5 asymmetric center has now been assigned through synthesis. GEX1Q1 displayed slightly better spliceosome inhibitory activity over its C-5 epimer. The salient features of this synthesis include an asymmetric hetero-Diels-Alder reaction to construct the tetrahydropyran ring and a Suzuki cross-coupling to assemble the key segments.,10.1021/ol501345d,2014-05-28,0.6420730763351564
Synthesis,Synthetic Studies on the Sporolides: Exploration of the Enediyne Route,"Synthetic studies towards the construction of the cyclopenta[a]indene fragment of the heptacyclic marine metabolite sporolide are reported based on a hypothetical biosynthesis. The key step of this biogenetic proposal includes a Bergman cyclization of an enediyne precursor. The enediyne target of this synthetic study was prepared by Sonogashira cross-coupling of two fragments, of which the cyclopentane fragment was prepared from cyclopentenone, Morita-Baylis-Hillman reaction, and enantioselective Sharpless dihydroxylation.",10.1055/s-0029-1218608,2009-12-16,0.6420706371650863
Synlett,A Convergent Synthesis of the <i>tris</i>-Oxazole Ring System in Ulapualide A and Related Marine Metabolites,"All articles of this category A convergent synthesis of the fully functionalised tris -oxazole system 16 , found in the ulapualide family of marine macrolides, involving elaboration of the substituted oxazoles 13 and 8 , followed by their coupling to the amide 14 and manipulation of the third oxazole ring via the oxazoline intermediate 15 , is described. tris -oxazoles - ulapualides",10.1055/s-1997-1056,2000-12-31,0.6420631105711992
Synthesis,A Practical and Efficient Synthesis of (±)-Anatabine,"A new efficient synthesis of racemic anatabine is reported. The title target was obtained in an excellent overall yield of 70%, by a five-step synthesis, using cheap reagents and mild reaction conditions.",10.1055/s-0036-1591538,2018-02-12,0.6420400267891035
Organic Process Research & Development,Synthesis of the Hepatitis B Nucleoside Analogue Lagociclovir Valactate,"2′,3′-Dideoxy-3′-fluoro-5- O -[(S)-(+)-2-( l -valyloxy)-propionyl] guanosine (lagociclovir valactate) is a prodrug of 3′-fluoro-2′,3′-dideoxyguanosine with high oral bioavailability in humans and potent activity against hepatitis B virus (HBV). A five-step synthesis of lagocyclovir valactate starting from 2-amino-6-chloropurine is described. The synthesis was performed at kilogram scale, and the target nucleoside prodrug was isolated as the hemisulphate salt with an overall yield of 23%. The major challenges were N-glycosylation of a 2-deoxyfluorosugar, which required separation of α- and β-anomers, and deprotection of the penultimate intermediate by hydrogenation.",10.1021/op200153s,2011-08-03,0.6420397697942394
Tetrahedron,Synthesis of new chiral σ2λ2-phosphenium cations,,10.1016/s0040-4039(99)00841-2,1999-06-01,0.6420341615360368
Synlett,First Synthetic Approach to Spongian Pentacyclic Diterpenoids. Enantioselective Synthesis of Dendrillol-1,"All articles of this category The enantioselective synthesis of the spongian diterpene dendrillol-1 ( 3 ), from chiral (+)-podocarp-8(14)-en-13-one ( 5 ) of known absolute configuration, is described. Key intermediate in this synthesis is the acid-dialdehyde 4 (8,14-diformylpodocarpane-13-carboxylic acid), which was prepared from 5 by a reaction sequence involving photo-addition of acetylene, nucleophilic carboxylation, reductive dehydroxylation, and ozonolysis.",10.1055/s-1991-20876,1991-01-01,0.6420340447505389
Organic Letters,Total Synthesis of Paracaseolide A,"The total synthesis of paracaseolide A, a valuable cell-cycle progression inhibitor, was accomplished in 8 steps from known compounds, with 6.6% overall yield. The synthetic strategy creates strong potential for diversification.",10.1021/ol303447r,2013-01-16,0.6420033594396343
Journal of the American Chemical Society,Total Synthesis of (−)-Strychnine,"Total synthesis of (-)-strychnine is described. Notable features of our synthesis include (1) palladium-catalyzed coupling of the indole and vinyl epoxide moieties, (2) synthesis of the nine-membered cyclic amine derivative from the diol precursor in a one-pot procedure, and (3) transannular cyclization of the nine-membered cyclic amine.",10.1021/ja046407b,2004-07-29,0.6419781036526085
Journal of the American Chemical Society,Total Synthesis of (+)-Perophoramidine and Determination of the Absolute Configuration,"The first asymmetric total synthesis of (+)-perophoramidine has been achieved in 17 steps with ∼11% overall yield. The key step relies on an asymmetric biomimetic Diels-Alder reaction between the in situ-generated chiral diene T-24 and the substituted tryptamine 23 to assemble the core structure 27a in a highly efficient way. An acid-catalyzed thermodynamic equilibrium results in C═N double-bond migration of the amidine moiety in 37, which guarantees a regioselective methylation on N(1) at the end of the synthesis. The absolute configuration of (+)-perophoramidine was determined by X-ray crystallographic analysis of the chiral intermediate 32 and comparison of the rotation of synthetic (+)-perophoramidine with that of the natural product.",10.1021/ja1070043,2010-09-21,0.6419708624101065
Journal of the American Chemical Society,Total Syntheses of Lyconadins A–C,"The total synthesis of the Lycopodium alkaloid lyconadin A was accomplished and it was applied to the total syntheses of the related congeners, lyconadins B and C. Lyconadin A has attracted attention as a challenging target for total synthesis due to the unprecedented pentacyclic skeleton. Our synthesis of lyconadin A features a facile construction of the highly fused tetracyclic skeleton through a combination of an aza-Prins reaction and an electrocyclic ring opening, followed by formation of a C-N bond. Transformation of the bromoalkene moiety of the tetracycle to a key enone intermediate was extensively investigated, and three methods via sulfide, oxime, or azide intermediates were established. A pyridone ring was constructed from the key enone intermediate to complete the synthesis of lyconadin A. A dihydropyridone ring could also be formed from the same enone intermediate, leading to a synthesis of lyconadin B. Establishment of the conditions for an electrocyclic ring opening without formation of the C-N bond resulted in completion of the total synthesis of lyconadin C.",10.1021/ja312065m,2013-01-18,0.641961335802549
Journal of Organic Chemistry,Total Synthesis of (+)-Irciniastatin A (a.k.a. Psymberin) and (−)-Irciniastatin B,"A unified synthetic strategy to access (+)-irciniastatin A (a.k.a. psymberin) and (-)-irciniastatin B, two cytotoxic secondary metabolites, has been achieved. Highlights of the convergent strategy comprise a boron-mediated aldol union to set the C(15)-C(17) syn-syn triad, reagent control to set the four stereocenters of the tetrahydropyran core, and a late-stage Curtius rearrangement to install the acid-sensitive stereogenic N,O-aminal. Having achieved the total synthesis of (+)-irciniastatin A, we devised an improved synthetic route to the tetrahydropyran core (13 steps) compared to the first-generation synthesis (22 steps). Construction of the structurally similar (-)-irciniastatin B was then achieved via modification of a late-stage (-)-irciniastatin A intermediate to implement a chemoselective deprotection/oxidation sequence to access the requisite oxidation state at C(11) of the tetrahydropyran core. Of particular significance, the unified strategy will permit late-stage diversification for analogue development, designed to explore the biological role of substitution at the C(11) position of these highly potent tumor cell growth inhibitory molecules.",10.1021/jo400260m,2013-03-19,0.6419502985733468
Synlett,Synthesis of Alaremycin,Methyl 5-azido-4-oxohexanoate was synthesized from 5-hexenoic acid in six steps and converted to the title compound by NaReO4- and CF3SO3H-catalyzed reaction in Ac2O/CCl4 followed by hydrolysis of the methyl ester moiety.,10.1055/s-2006-926237,2006-02-06,0.6419337714345466
Organic Letters,SmI<sub>2</sub>-Mediated Cross-Coupling of Nitrones with β-Silyl Acrylates: Synthesis of (+)-Australine,"The SmI(2)-mediated cross-coupling of nitrones with β-silyl-α,β-unsaturated esters, followed by zinc reduction, allows an efficient and highly diastereoselective preparation of β-silyl lactams, which are precursors of β-hydroxy lactams through Tamao-Fleming oxidation. By applying the method to a cyclic, carbohydrate-derived nitrone, a new synthesis of (+)-australine has been realized in only 11 steps and in 21% overall yield from L-xylose.",10.1021/ol203396s,2012-01-31,0.6418942991152234
Angewandte Chemie International Edition,"Asymmetric, Protecting‐Group‐Free Total Synthesis of (−)‐Englerin A",The golden touch: Total synthesis of natural (−)-englerin A from (R)-citronellal has been achieved using a gold-catalyzed cyclization as the key step (see scheme). No protecting-group manipulations were required in the synthetic sequence.,10.1002/anie.201000888,2010-04-07,0.6418897918157238
Journal of Organic Chemistry,"Enantioselective Total Synthesis of (1<i>R</i>,3<i>S</i>,4<i>R</i>,5<i>R</i>)-1-Amino-4,5-dihydroxycyclopentane-1,3-dicarboxylic Acid. A Full-Aldol Access to Carbaketose Derivatives","The enantioselective synthesis of cyclopentanedicarboxylic amino acid 1, a novel rigid and functionalized L-glutamic acid analogue, has been achieved in 15 linear steps from silyloxypyrrole 3, utilizing L-glyceraldehyde 4 as the source of chirality. The key steps in the synthesis are three sequential aldol-based carbon-carbon bond-forming reactions: two crossed vinylogous aldol additions (2 + 3 --> 8 and 4 + 5 --> 10 + 11) and one intramolecular silylative aldolization (6 --> 7). En passant, the short syntheses of (2S)-2-hydroxymethylglutamic acid (16) and its (2R)-enantiomer ent-16, a potent metabotropic glutamate receptor agonist, have been achieved.",10.1021/jo035846a,2004-03-04,0.6418781901791799
Journal of the American Chemical Society,Enantiocontrolled Total Synthesis of (−)-Retigeranic Acid A,"The asymmetric total synthesis of (−)-retigeranic acid A has been realized. The key features of the current synthesis include (1) a Pt-catalyzed Conia-ene 5- exo-dig cyclization of enolyne to establish the key quaternary stereochemical center of C-10 (D/E ring), (2) an intramolecular diastereoselective Prins cyclization to construct the trans -hydrindane backbone (A/B ring), and (3) a late-stage intramolecular Fe-mediated hydrogen atom transfer (HAT) Baldwin-disfavored 5- endo - trig radical cyclization to rapidly assemble vicinal quaternary centers and the core structure of (−)-retigeranic acid A (C ring).",10.1021/jacs.3c04850,2023-06-12,0.6418766403582388
Tetrahedron,A conceptually new route to optically active carba-prostacyclins: synthesis of exocyclic alkenes via doubly lithiated allyl sulfones,,10.1016/s0040-4039(00)80208-7,1988-01-01,0.641866717829024
Journal of Organic Chemistry,Total Synthesis of <i>ent</i>-Ascospiroketal B,"Ascospiroketal B was isolated from a marine-derived fungus as a structurally unique polyketide possessing a rare tricyclic core including 5,5-spiroketal-γ-lactone. An asymmetric total synthesis of ent-ascospiroketal B was achieved using an original synthetic route. The synthesis included the stereoselective construction of 5,5-spiroketal for ascospiroketal B and stereocontrolled construction of a quaternary asymmetric carbon by rearrangement of a trisubstituted epoxide.",10.1021/acs.joc.7b02925,2018-02-01,0.6418647403007725
Organic Process Research & Development,"A Scalable Process to the Key Intermediate of Cilazapril, (<i>S</i>)-1-Benzyloxycarbonylhexahydropyridazine-3-carboxylic Acid, Through a Novel Cascade Course","A novel and efficient manufacturing technology is disclosed in the present work for the preparation of ( S )-1-benzyloxycarbonylhexahydropyridazine-3-carboxylic acid, which is a key intermediate of cilazapril. The whole process includes only three steps; the first two steps were conducted in one pot, followed by a novel selective removal of a Cbz group in a cascade course.",10.1021/op400155u,2013-07-29,0.6418545823549583
European Journal of Organic Chemistry,Synthesis of the Spiroketal Fragment of (–)‐Ushikulide A,Abstract The stereoselective synthesis of the spiroketal fragment of the immunosuppressant (–)‐ushikulide A is described. The salient feature of this synthesis is the construction of the spiroketal moiety by hydrolysis of a dialkylated tosylmethyl isocyanide derivative derived from alkylation of tosylmethyl isocyanide (TosMIC) with suitably substituted halohydrin derivatives. The key functionalized tetrahydropyran ring was constructed by using Prins cyclization of the α‐acetoxy ether.,10.1002/ejoc.201402196,2014-07-21,0.6418476279435016
Angewandte Chemie International Edition,Total Synthesis of (+)‐Alstonlarsine A,"Abstract An enantioselective total synthesis of (+)‐alstonlarsine A ( 1 ), a monoterpenoid indole alkaloid possessing a unique pentacyclic skeleton as well as a rare biological activity, is achieved. The key step is an efficient domino sequence, comprising enamine formation followed by an inverse‐electron‐demand intramolecular dearomative Diels–Alder cycloaddition for the construction of 9‐azatricyclo[4.3.1.0 3,8 ]decane core. The key intermediate for this domino sequence was synthesized by a newly developed methodology, relying on indole C (2) ‐H bond functionalization, combined with intramolecular Horner–Wadsworth–Emmons reaction. This tactical combination offers a new general entry into other (privileged) tricyclic frameworks possessing indole ring fused to 6‐, 7‐ or 8‐membered rings.",10.1002/anie.202210297,2022-08-08,0.6418014386295179
Organic Letters,Asymmetric Total Synthesis of (+)-Strychnine,"A synthetic strategy for the catalytic asymmetric total synthesis of (+)-strychnine is disclosed. Key features of this synthesis include an organocatalytic enantioselective Michael addition to establish the chirality of the starting building block, a photoinduced radical cascade reaction to access the Corynanthe alkaloid intermediate, and a bioinspired cascade rearrangement to generate the core of the Strychnos alkaloids.",10.1021/acs.orglett.8b03686,2018-12-18,0.6417865494576481
Organic Process Research & Development,"Construction of a (3<i>aR</i>,4<i>R</i>,9<i>bR</i>)-Hexahydropyrroloquinoline by Stereoselective Hydrogen-Mediated Domino Cyclization","A novel practical asymmetric route to a chiral hexahydropyrroloquinoline derivative 2, a key fragment of TAK-480, is reported. The corresponding substrate, enamine 19, was directly transformed to a diastereopure and enantiopure (3 aR,4 R,9 bR )-hexahydropyrroloquinoline 16 through a rhodium-catalyzed hydrogen-mediated domino cyclization consisting of four steps; (1) asymmetric hydrogenation of enamine, (2) hydrogenation of iminium olefin in a lactam, (3) dehydration and catalytic sulfonation, and (4) cis -selective intramolecular cyclization. A tuned asymmetric catalyst [Rh(cod){(2 S,4 S )-PTBP-SKEWPHOS}]OTf that we previously developed was found to promote improved reaction activity and be the most suitable catalyst for a multikilogram manufacturing for preclinical research. The resulting stereoselective domino cyclization drastically reduced several synthetic steps, and the resulting waste compared to the discovery route that required chiral preparative high-performance liquid chromatography and silica gel column separation.",10.1021/acs.oprd.8b00365,2019-02-20,0.6417727343551156
Journal of Organic Chemistry,Total Synthesis of Alternariol,"Total synthesis of alternariol, a toxic secondary metabolite of various Alternaria fungi, was achieved in seven steps starting with orcinol and 3,5-dimethoxybromobenzene. The longest linear sequence consists of six steps. Key reaction is a palladium-catalyzed Suzuki-type coupling of an orcinol-derived boronic acid with a brominated resorcylic aldehyde. The final demethylation furnished alternariol in 73% yield containing a smaller fraction of alternariol 9-methyl ether (approximately 20%).",10.1021/jo050075r,2005-03-05,0.641755953022164
Journal of Organic Chemistry,Concise Formal Total Synthesis of Hybocarpone and Related Naturally Occurring Naphthazarins,"A concise formal total synthesis of the cytotoxic bisnaphthazarin derivative hybocarpone has been completed through the development of routes to the synthetic precursor, 3-ethyl-2-hydroxy-5,7,8-trimethoxy-6-methyl-1,4-naphthoquinone. The oxidation of 3-ethyl-1,2,4,5,7,8-hexamethoxy-6-methylnaphthalene under Rapoport conditions gave 3-ethyl-2-hydroxy-5,7,8-trimethoxy-6-methyl-1,4-naphthoquinone in modest yields after basic hydrolysis. In addition, treatment of 3-ethyl-1,2,4,5,7,8-hexamethoxy-6-methylnaphthalene with boron tribromide provided access to the naturally occurring naphthazarin, boryquinone. The analogous oxidative demethylation of 3,6-dimethyl-1,2,4,5,7,8-hexamethoxynaphthalene and 3-ethyl-1,2,4,5,7,8-hexamethoxynaphthalene resulted in the synthesis of 2,5,7,8-tetrahydroxy-3,6-dimethyl-1,4-naphthoquinone (aureoquinone) and 3-ethyl-2,5,7,8-tetrahydroxy-1,4-naphthoquinone, respectively. An alternative selective synthetic route to 3-ethyl-2-hydroxy-5,7,8-trimethoxy-6-methyl-1,4-naphthoquinone was also developed utilizing an intramolecular Claisen condensation of methyl 2-butyryl-3,5,6-trimethoxy-4-methylphenylacetate with concomitant in situ aerial oxidation.",10.1021/jo0519561,2005-12-30,0.6417272090673618
Angewandte Chemie International Edition,An Enantioselective Total Synthesis of (+)‐Peloruside A,"Short and sweet: Chiral epoxides, prepared using (salen)cobalt-catalyzed ring-opening reactions, and a chromium catalyst controlled hetero-Diels–Alder reaction were used to set most of the stereocenters in the total synthesis of the microtubule-stabilizing agent peloruside A. The overall highly convergent route required only 20 steps in the longest linear sequence. MOM=methoxymethyl, TBS=tert-butyldimethylsilyl.",10.1002/anie.201002177,2010-06-28,0.6417243660467639
Organic Process Research & Development,Process Development and Scale-Up of the Potential Thiazolidinedione Antidiabetic Candidate PNU-91325,"An efficient six-step synthesis has been developed for the preparation of the thiazolidinedione analogue PNU-91325 ( 3 ) from the commercially available olefin 12 . This process involves a novel epoxide ring opening with a deactivated phenol under phase-transfer conditions. Significant improvements were made in the oxidation of a secondary alcohol to the ketone and the 1,4-reduction of an enone from a previous process. Overall, this route allows for the preparation of PNU-91325 in 25% yield.",10.1021/op025549s,2002-08-16,0.641720847885406
Journal of Organic Chemistry,Synthesis of (−)-Epi-Indolactam V by an Intramolecular Buchwald–Hartwig C–N Coupling Cyclization Reaction,"The synthetic efforts toward the concise synthesis of (-)-indolactam V from simple and commercially available starting materials using palladium- and copper-catalyzed intramolecular N-arylation strategy for the elaboration of the requisite nine-membered lactam ring as the key step are described. The incorporation of a turn-inducing structural element along the linear precursor was fundamental to achieve the heterocyclization step as well as obtain the correct regio- and chemoselectivity. The stereoselective nature in the C-N coupling cyclization reaction is interpreted in terms of minimization of allylic strain at the transition state for the palladium-amido complex formation. Meanwhile, the synthesis of the (-)-epi-indolactam V and its enantiomer have been accomplished.",10.1021/jo4013767,2013-07-11,0.6416965283117767
Synthesis,Total Synthesis of (±)-Cassumunins A–C and Curcumin Analogues,"A full account of the total synthesis of (±)-cassumunins A–C – superior antioxidants and anti-inflammatory agents – is given. Two novel approaches were developed for synthesizing cassumunins. The total synthesis of cassumunins A and B was accomplished in five linear steps from a known aldehyde in good overall yields of 50 and 43%, respectively, featuring a cascade [3,3]-sigmatropic shift (the Claisen rearrangement) and Heck cross-coupling reaction. Consequently, the total synthesis of cassumunin C was accomplished in three linear steps from a known alcohol with an overall yield of 53%. The key features involved in this synthesis are tandem [3,3]-sigmatropic shift, SN2′ reaction, and aldol condensation. Moreover, a total of eighteen symmetrical and unsymmetrical curcumin analogues were synthesized.",10.1055/s-0039-1690794,2020-01-27,0.6416917583660122
Organic Process Research & Development,Diastereospecific Enolate Addition and Atom-Efficient Benzimidazole Synthesis for the Production of L/T Calcium Channel Blocker ACT-280778,"A scalable access to 1 ( ACT-280778 ), a potent L/T calcium channel blocker, has been developed. The synthesis, amenable to kilogram manufacturing, comprises 10 chemical steps from enantiomerically pure 5-phenylbicyclo[2.2.2]oct-5-en-2-one ( 3 ) and 1,4-dimethoxybenzene with a longest linear sequence of 7 steps. Key to the success of this fit-for-purpose approach are a robust and atom-efficient access to benzimidazole 4, the substrate-controlled diastereoselective enolate addition toward carboxylic acid 2 that was isolated by simple crystallization with high dr (>99:1), the convenient selective N -deacylation of intermediate 10, and the identification of a suitable solid form of 1 as the bis-maleate salt ( 1 · 2 C 4 H 4 O 4 ). As an illustration of the robustness of this process, 14 kg of drug substance, suitable for human use, was produced with an overall yield of 38% over the longest linear sequence (7 steps).",10.1021/op400269b,2014-01-13,0.6416853417673994
Journal of Organic Chemistry,Double Ring Expansion Strategy for Fused 3-Benzazepines: Alternative Synthesis of the Dolby–Weinreb Enamine,"A double ring expansion strategy for constructing fused 3-benzazepines is described. The oxidative ring expansion of spiroamine compounds with N -chlorosuccinimide and subsequent ring expansion of the resulting ketiminium ion intermediates with trimethylsilyldiazomethane afforded fused 3-benzazepines in a one-pot operation. Importantly, the Dolby–Weinreb enamine, which is a key synthetic intermediate for harringtonine alkaloids, cephalotaxines, can be accessed from commercial materials in only two steps using our developed method.",10.1021/acs.joc.2c02475,2022-12-08,0.6416613625766384
Organic Process Research & Development,Optimized Kilogram-Scale Synthesis and Impurity Identification of SHEN26 (ATV014) for Treating COVID-19,"SHEN26, a 5′-cyclohexane-carboxylate prodrug of the nucleoside analog GS-441524, is a potent RdRp inhibitor currently undergoing phase III clinical trials for coronavirus disease 2019 (COVID-19) treatment. To meet clinical demands and future market supply, it is essential to develop preparation methods suitable for industrial manufacture. In this study, we provide a 3-step industrial synthesis method for SHEN26 with chromatography-free postreaction treatments. 10-kg-scale synthesis was achieved with a total of 57% yield. Impurities in the synthesis process of SHEN26 were also identified and analyzed. The purity of GMP-graded active pharmaceutical ingredient (API) reached 98.9% (<1.1% impurity), demonstrating the viability of this synthetic route for large-scale manufacture of SHEN26.",10.1021/acs.oprd.3c00248,2023-11-20,0.6416593798245398
Journal of Organic Chemistry,Skeletal Reorganization: Synthesis of Diptoindonesin G from Pauciflorol F,"Described herein is a novel synthetic approach to diptoindonesin G, a highly potent anticancer oligostilbenoid natural product, from pauciflorol F pentamethyl ether through a skeletal reorganization strategy where oxidative cleavage of the indanone ring system of pauciflorol F and sequential cyclization of the key intermediate allowed direct access to the target skeleton.",10.1021/acs.joc.7b03089,2018-01-11,0.6416462555908502
Synthesis,"Total Synthesis of Lucidumone: Attempted Shortcuts, Dead Ends and Lessons Learnt","Abstract Lucidumone is a meroterpenoid isolated from the mushroom Ganoderma lucidum, displaying selective COX-2 inhibitory activity. In this work, we detail our synthetic efforts which led to the first enantioselective synthesis of lucidumone in 13 steps (longest linear sequence). Beyond the key retro-[4+2]/intramolecular Diels–Alder cascade, we discuss the difficulties regarding fragment assembly, introduction of the methyl ketone moiety and choice of adequate protecting group.",10.1055/s-0042-1751529,2023-12-04,0.6416321534709435
Organic Letters,Enantioselective Total Synthesis of (+)-Lithospermic Acid,"An enantioselective synthesis of (+)-lithospermic acid, a potent anti-HIV agent, has been accomplished in a convergent manner in nine steps. The synthesis features an enantioselective intramolecular oxa-Michael addition catalyzed by a quinidine derivative, a hypervalent iodine-mediated rearrangement of chromanone to dihydrobenzofuran, an enantioselective α-oxyamination, and an intermolecular C-H olefination.",10.1021/ol302273r,2012-09-14,0.6416052076624043
Synthesis,An Improved One-Pot Synthesis of Phospholes,,10.1055/s-1981-29670,1981-01-01,0.6415921351942628
Tetrahedron,Iminosugar thioglycosides as glycosyl donors: a route to disaccharides with an iminosugar moiety,,10.1016/j.tetlet.2007.11.160,2007-12-04,0.6415822665610347
Journal of the American Chemical Society,Total Synthesis of (±)-Tazettine,"The total synthesis of (±)-tazettine ( 1 ) has been achieved in 16 steps from commercially available piperonyl alcohol in 11% overall yield. The crucial quaternary center was assembled by a novel [4+1] cycloaddition between dimethoxycarbene and β-aryl vinyl isocyanate ( 4 ). Samarium diiodide conditions were employed to reduce the enamide unsaturation in the [2]benzopyrano[3,4- c ]hydroindole intermediate 19 to compound 20 exhibiting a cis -AB ring fusion.",10.1021/ja974317j,1998-04-01,0.6415813217961445
Journal of Organic Chemistry,Synthesis of the Erythrina Alkaloid Erysotramidine,A concise synthesis of erysotramidine (an alkaloid belonging to the erythrina family) was achieved starting with an inexpensive phenol and amine derivative. The synthesis is based on oxidative phenol dearomatizations mediated by a hypervalent iodine reagent and includes a novel route to a key indolinone moiety.,10.1021/jo501583c,2014-08-20,0.6415759565589648
Angewandte Chemie International Edition,Divergent Asymmetric Total Synthesis of Mulinane Diterpenoids,"A concise, divergent, asymmetric total syntheses of mulinane diterpenoids has been achieved. Specifically, a new strategy was developed featuring a key intramolecular Friedel-Crafts reaction to construct the chiral fused 5-6-6 tricyclic motif, followed by sequential Birch reduction, conjugate methylation, and homologation/ring-expansion reactions to furnish the desired 5-6-7 tricyclic skeleton bearing five contiguous stereocenters. With this efficient strategy, seven mulinane diterpenoids and two analogues were synthesized via late-stage functional modification or functionalization in 8.6-20 % overall yields and 11-15 steps.",10.1002/anie.201706994,2017-08-14,0.6415664724175167
Tetrahedron,"Enantioselective total synthesis of (+)-panepophenanthrin, a novel inhibitor of the ubiquitin-activating enzyme",,10.1016/j.tetlet.2003.12.149,2004-01-27,0.641559378398829
Journal of Organic Chemistry,Total Synthesis of (±)-2-Pupukeanone,A synthesis of (±)-2-pupukeanone ( 4 ) is described in which the pupukeanane skeleton is assembled by means of intramolecular cyclization of tosylate 11 and then the attachment of an isopropyl group at the appropriate position of the tricyclic ring system. The key intermediate 11 was constructed via a sequence begining from readily available ketone 5 and proceeding through bicyclo[3.2.1]ketone 8 by regioselective ring expansion.,10.1021/jo9603338,1996-01-01,0.6415590511403545
Journal of the American Chemical Society,Total Synthesis of Desferrisalmycin B,"The first total synthesis of a naturally occurring siderophore antibiotic, desferrisalmycin B, is described, and the configuration of the unknown stereocenter is assigned. The synthesis features a synthetic strategy of constructing the novel amino-heptopyranoside component by stereoselective dihydroxylation followed by a Bose-modified Mitsunobu reaction. Through this convergent approach, other members of salmycins should also be synthetically accessible.",10.1021/ja028386w,2002-11-20,0.6415537244172792
Synthesis,"Diastereoselective Synthesis of Novel and Enantiopure Tetrahydropyrano[3,2-c]quinolines","Diastereoselective synthesis of novel and enantiopure N-alkylated tetrahydropyrano[3,2- c ]quinolines is described via intramolecular Friedel–Crafts alkylation using a 1- O -acetylglucosyl derivative as the key intermediate. Unprecedented formation of new glycal derivatives and α,β-unsaturated carbaldehyde products is also discussed.",10.1055/s-0035-1560174,2015-08-27,0.6415534180788424
Tetrahedron,A simple and an effective route to caryophyllene system - synthesis of DL-isocaryophyllene,,10.1016/s0040-4039(00)93151-4,1976-06-01,0.6415498574886143
Journal of the American Chemical Society,Total Synthesis and Determination of the Absolute Configuration of Frondosin B,"Two concise syntheses of (+/-)-frondosin B (1), an interleukin-8 receptor antagonist, have been achieved from commercially available 5-methoxysalicylaldehyde. The seven-membered ring in ketone 33, the common intermediate for both syntheses, was built by a classical Friedel-Crafts reaction. The key step of the first route was facile cationic cyclization of the vinylogous benzofuran to the trisubstituted olefin (30 --> 16 + 38) to construct a six-membered carbocycle. Although this route demonstrated the efficacy of the stepwise approach to the frondosin ring-system, it also resulted in olefinic isomers that were easily isomerized in acidic conditions. In the second route, we utilized a Diels-Alder reaction between sterically demanding diene 42 and nitroethylene to fix the double bond in its required position in the resultant dimethylcyclohexane ring. A third total synthesis was devised for the purpose of determining the absolute configuration of frondosin B. It reached diene 42, this time in the enantiomerically defined form. From this point, naturally configured frondosin B was obtained in the enantiomerically enriched form. These studies establish the absolute configuration of the secondary methyl center in frondosin B to be R.",10.1021/ja0021060,2001-02-10,0.641537410564199
Organic Process Research & Development,Reiterative Chiral Resolution/Racemization/Recycle (RRR Synthesis) for an Effective and Scalable Process for the Enantioselective Synthesis of a Dual IDO1/TDO2 Inhibitor Imidazoisoindole Derivative,"Herein, we report an effective and scalable highly enantioselective synthesis of an 5H-imidazo[5,1- a ]isoindole derivative via an RRR-synthesis approach (resolution–racemization–recycle). Chiral resolution performed with the aid of 2,3-dibenzoyl- d -tartaric acid allowed the obtaining of the desired enantiomer in high enantiopurity (>99% ee) and good yield. The undesired enantiomer was subjected to racemization under basic conditions and again to resolution, improving the efficiency of the entire process. The asymmetric formation of the new stereocenter in an early stage of the synthesis scheme was also investigated by means of organocatalytic systems.",10.1021/acs.oprd.0c00004,2020-04-30,0.6415030304919422
Organic Process Research & Development,Preparation of a HMG-CoA Reductase Inhibitor via an Optimized Imidazole-Forming Condensation Reaction,"Development work toward an enabling synthesis of preparative scale batches of an imidazole-based HMG-CoA reductase inhibitor is described. The desired target was synthesized in 16% yield over 7 steps, highlighted by an imidazole-forming condensation reaction in which the yield was improved from 20% to >70% via modification of the solvent, acid, and amine equivalents. The step 2 acylation was improved, and a problematic benzyl ester in step 4 was converted into the corresponding benzyl amide to decrease trans-amidation during the step 5 imidazole formation. A highly effective salt formation and crystallization protocol was also developed.",10.1021/op800092e,2008-09-27,0.6414796480666973
Journal of Organic Chemistry,A Concise Total Synthesis of (+)-FR900482 and (+)-FR66979,"The concise, enantioselective total synthesis of the potent antitumor antibiotics (+)-FR900482 and (+)-FR66979 are described. Sharpless asymmetric epoxidation technology has been deployed to construct the optically active aziridine-containing fragment that is joined to the aromatic moiety in a highly convergent manner. Dimethyldioxirane effects the remarkable one-step deprotection/oxidative cyclization of an eight-membered ring amino-ketone to the unique hydroxylamine hemiketal ring system that is a distinctive structural motif of FR900482. This reaction has been exploited in a concise 33-step enantioselective total synthesis of FR900482.",10.1021/jo035828t,2004-03-20,0.6414763388674635
Journal of Organic Chemistry,A Convenient Synthesis of (<i>S</i>)-H<sub>4</sub>-BINOL and Its Derivatives via Hydrogenation of Monoesters of BINOL,"A new multigram synthesis of chiral (S)-H(4)-BINOL and its derivatives in moderate to high yield (up to 83% total yield) via monoesterification of (S)-BINOL, hydrogenation, and saponification reaction was described. The two new monomethylated (S)-H(4)-BINOL obtained may be useful materials in asymmetric catalysis.",10.1021/jo802542m,2009-01-26,0.6414751316345002
Tetrahedron,Practical synthesis of tetrasubstituted thiophenes for use in compound libraries,,10.1016/s0040-4039(99)01108-9,1999-07-01,0.6414721552926682
Synthesis,Total Synthesis of Rhoiptelol B,"A simple and efficient total synthesis of rhoiptelol B, isolated from the the leaves and fruits of Rhoiptelea chiliantha, is achieved using Sharpless asymmetric epoxidation, 1,3-anti-chiral allylation, olefin cross-metathesis, Sharpless asymmetric dihydroxylation, and ferric chloride catalyzed intramolecular SN2 cyclization as the key steps.",10.1055/s-0030-1258319,2010-10-28,0.6414469797485037
Journal of Organic Chemistry,Asymmetric Synthesis of (+)-<i>anti</i>- and (−)-<i>syn</i>-Mefloquine Hydrochloride,"The asymmetric (er > 99:1) total synthesis of (+)-anti- and (-)-syn-mefloquine hydrochloride from a common intermediate is described. The Sharpless asymmetric dihydroxylation is the key asymmetric transformation used in the synthesis of this intermediate. It is carried out on an olefin that is accessed in three steps from commercially available materials, making the overall synthetic sequence very concise. The common diol intermediate derived from the Sharpless asymmetric dihydroxylation is converted into either a trans- or cis-epoxide, and these are subsequently converted to (+)-anti- and (-)-syn-mefloquine, respectively. X-ray crystallographic analysis of derivatives of (+)-anti- and (-)-syn-mefloquine is used to lay to rest a 40 year argument regarding the absolute stereochemistry of the mefloquines. A formal asymmetric (er > 99:1) synthesis of (+)-anti-mefloquine hydrochloride is also presented that uses a Sharpless asymmetric epoxidation as a key step.",10.1021/acs.joc.6b01476,2016-09-22,0.6414455187327036
Journal of Organic Chemistry,Highly Stereoselective and Scalable Synthesis of <i>trans</i>-Fused Octahydrocyclohepta[<i>b</i>]pyrrol-4(1<i>H</i>)-ones via the Aza-Cope–Mannich Rearrangement in Racemic and Enantiopure Forms,We have developed an efficient and stereoselective route to trans-fused octahydrocyclohepta[b]pyrrol-4(1H)-ones. The key features of our synthesis include the regioselective epoxide ring-opening of alkynyl oxiranes and a stereoselective aza-Cope-Mannich reaction. The target compounds were prepared in 3-6 steps from commercially available starting materials (61-75% overall yield) with minimal chromatographic purification. We have devised an stereoselective route to target compounds using Shi epoxidation or (R)-1-phenylethylamine as a source of chirality.,10.1021/jo301762a,2012-10-31,0.6414375801357575
European Journal of Organic Chemistry,A New Secondary Metabolite from <i>Alternaria Alternata</i>: Structure Elucidation and Total Synthesis of Altenuic Acid IV,"A putative intermediate in the biosynthesis of altenuic acids I–III was isolated from Alternaria alternata in the 1950ies and a sample survived over the decades. This resorcylic lactone named altenuic acid IV is a composite of a resorcylic and a muconic acid. Its structure was confirmed by NMR spectroscopy and by total synthesis. Altenuic acid IV was here obtained starting with 2‐bromo‐4,6‐dimethoxybenzene and 4‐methylbenzene‐1,2‐diol with a total yield of 20 %. The synthesis was achieved in ten steps where the longest sequence consists of seven steps. Key steps were an oxidative ring opening of a bromocresol furnishing a bromomuconate and its Suzuki coupling with a resorcylate‐derived boronate.",10.1002/ejoc.201801801,2019-02-05,0.641418144161597
Journal of the American Chemical Society,"Total Synthesis of Isodihydrokoumine, (19<i>Z</i>)-Taberpsychine, and (4<i>R</i>)-Isodihydroukoumine <i>N</i><sub>4</sub>-Oxide",We report the total synthesis of the natural products isodihydrokoumine and (19 Z )-taberpsychine in 11 steps each and (4 R )-isodihydrokoumine N 4 -oxide in 12 steps from commercially available starting materials. The key reactions include an intramolecular [3 + 2] nitrone cycloaddition and Lewis acid mediated cyclizations of a common intermediate to provide the core structures of either taberpsychine or isodihydrokoumine.,10.1021/jacs.8b05095,2018-06-25,0.6414098116227008
Synthesis,A Convenient Synthesis of L-α-Vinylglycine from L-Homoserine Lactone,"All articles of this category A procedure for the synthesis of L -α -vinylglycine from L-homoserine lactone is described. The route developed is convenient (only one chromatography step is required) and efficient (71%; ≥ 95% optical yield over 4 steps). Key features include the use of acid-labile protecting groups for the amino (Bod) and carboxyl (diphenylmethyl ester) groups, and the use of the phenylselenolate equivalent derived from sodium borohydride and diphenyl diselenide for L-homoserine lactone cleavage. L -α -vinylglycine - L-homoserine lactone - phenylselenolate anion - enantiocontrolled synthesis",10.1055/s-1996-4177,1996-01-01,0.6414043381889256
Synthesis,"Synthesis of (2S,3R,5R)-2-Azido-3,5-dihydroxynonadecane Sphingolipid Analogue",A concise and highly efficient synthesis of an enigmol analogue has been achieved. The synthetic strategy features Jacobsen’s hydrolytic kinetic resolution (HKR) and epoxide opening by alkynyl boranes as the key steps.,10.1055/s-0040-1707397,2020-05-18,0.641399643162811
Synthesis,Two New Syntheses of a 4-Aminopyrazole: Condensation of an N-Substituted Vinamidinium Salt with a Functionalized Hydrazine,Two novel syntheses of a key 4-aminopyrazole synthetic building block are described. Both routes avoid the potentially explosive precursors that were used in the previously patented route. A salt of a vinamidinium cation previously used in 5-aminopyrimidine synthesis was condensed with a protected hydrazine salt leading to a 4-aminopyrazole. Buchwald-type amination coupling has also been shown to yield the same compound.,10.1055/s-2007-966054,2007-05-24,0.6413984502768242
Angewandte Chemie International Edition,Enantioselective Total Synthesis of (−)‐Minovincine in Nine Chemical Steps: An Approach to Ketone Activation in Cascade Catalysis,"Dressed to the nines: The first enantioselective total synthesis of (-)-minovincine has been accomplished in nine chemical steps and 13 % overall yield. A novel, one-step Diels-Alder/β-elimination/conjugate addition organocascade sequence allowed rapid access to the central tetracyclic core in an asymmetric manner. Boc=tert-butoxycarbonyl, LG=leaving group, PMB=para-methoxybenzyl.",10.1002/anie.201305171,2013-09-02,0.6413799493958332
Tetrahedron,A convenient synthetic route to (+)-faranal; The trail pheromone of pharaoh's ant,,10.1016/s0040-4039(00)85322-8,1986-01-01,0.6413793072670829
Tetrahedron,A convenient synthetic route to the bacteriochlorin chromophore,,10.1016/0040-4039(91)80636-k,1991-06-01,0.6413793072670829
Journal of the American Chemical Society,Total Synthesis of (±)-Maoecrystal V,The total synthesis of racemic maoecrystal V has been accomplished. Key steps include an intramolecular Diels-Alder cyclization to rapidly construct the core system from simple starting materials and the creation of the A-C ring trans-fusion through intramolecular delivery of a hydrogen to the hindered β-face of the ring system.,10.1021/ja309905j,2012-11-05,0.6413778895598904
Angewandte Chemie International Edition,"Total Synthesis of (±)‐Nominine, a Heptacyclic Hetisine‐Type Aconite Alkaloid",The barrier has finally been lifted to the synthesis of hetisine-type alkaloids with the total synthesis of (±)-nominine (1) in 40 steps from 2-bromo-5-methoxyphenethyl iodide. Key steps in the construction of the architecturally complex polycyclic structure of this natural product were a radical cyclization of an enyne and a palladium-catalyzed intramolecular α arylation of an aldehyde.,10.1002/anie.200460332,2004-09-01,0.6413777841584518
Journal of Organic Chemistry,Aromatic Nucleophilic Substitution or CuI-Catalyzed Coupling Route to Martinellic Acid,"Condensation of beta-amino ester 8b with triflate 7 gives N-aryl amino ester 11, which is converted into 2-substituted 4-oxoquinoline 4 using an intramolecular Dieckmann reaction as the key step. CuI-mediated coupling of beta-amino ester 8a with 1,4-diiodobenzene followed by an intramolecular acylation and Pd-catalyzed carbonylation provide another manner to 4. Alkylation of 4 and subsequent reductive amination deliver the cyclic imine 14, which is transformed into triamine 3 by ordinary operations. Guanylation of 3 under mild condition followed by deprotection results in the synthesis of martinellic acid 1.",10.1021/jo026125z,2002-11-28,0.6413613410003812
Angewandte Chemie International Edition,The Total Synthesis of Proteasome Inhibitors TMC-95A and TMC-95B: Discovery of a New Method To Generate cis-Propenyl Amides,"Silatropic and ene-like bond reorganizations (see scheme, left) were the key steps in the first total synthesis of the title compounds, which only differ in stereochemistry at the remote C36 stereocenter. Other key steps include a Suzuki biaryl construction, a diastereofacial dihydroxylation reaction, and a macrolactamization.",10.1002/1521-3773(20020201)41:3<512::aid-anie512>3.0.co;2-r,2002-01-29,0.6413600404093922
Journal of Organic Chemistry,"Synthesis of Orthogonally Protected (2<i>S</i>)-2-Amino-adipic Acid (α-AAA) and (2<i>S</i>,4<i>R</i>)-2-Amino-4-hydroxyadipic Acid (Ahad)","(2S,4R)-2-amino-4-hydroxyadipic acid (Ahad) building block 45 was synthesized in 11 steps and 6.5% overall yield from commercially available materials. Key steps in stereocontrol were an asymmetric conjugate addition employing a proline-based catalyst and a syn-selective intramolecular-conjugate addition of an oxygen nucleophile to an α,β-unsaturated ester. To enable incorporation of α-amino-adipic acid (α-AAA) and Ahad into peptides, a truly orthogonal protecting group scheme was developed, encompassing an allyloxycarbonyl (Alloc) carbamate for Nα, a tert-butyl ester for the δ-COOH, an acetol ester for the α-COOH, and a tert-butyldimethylsilyl ether for the γ-hydroxy group of Ahad.",10.1021/jo400558t,2013-05-02,0.6413574908055888
Synlett,Synthesis of Macrocyclic Urea Kinase Inhibitors,"An efficient and convergent route was developed for the synthesis of a novel class of urea-based macrocyclic kinase inhibitors. The synthesis is featured with an efficient urea formation by using a key carbamate intermediate and with a smooth ring-closure olefin metathesis. Furthermore, the hydrogenations of the resulting olefins were investigated in this complex macrocyclic ring system.",10.1055/s-2007-991083,2007-10-12,0.6413490666549763
Synthesis,A Total Synthesis of the Aromatic Monoterpene Espintanol,A synthesis of the leishmanicidal and trypanocidal monoterpene espintanol from dimethyl 2-isopropyl-3-oxoglutarate and 2-butynal using a Michael addition-Dieckmann cyclization as the key step is described.,10.1055/s-2004-837305,2004-12-22,0.6413482313648107
Tetrahedron,"Highly efficient and selective displacement of alkylthio group on acylketene O,S-acetals by organocopper reagents: A novel route to 2-alkoxy/aryloxy-1-alkenylketones",,10.1016/0040-4039(95)01990-y,1995-12-01,0.6413457391775884
Journal of Organic Chemistry,Synthetic Studies toward the Total Synthesis of Swinholide. 1. Stereoselective Construction of the C<sub>19</sub>−C<sub>35</sub> Subunit,"The development of an approach directed at the total synthesis of the complex cytotoxic marine macrodiolide swinholide is described. The present study focuses on the development of a synthetic route for the preparation of the C 19 −C 35 segment of the structure, which is composed of a trisubstituted pyran moiety with a contrathermodynamic anti arrangement of the C 2 and C 6 pyran substituents (swinholide C 27 and C 31 ) which is joined by an ethano linker to an acyclic array containing five contiguous stereocenters. The pyran subunit was constructed using a stereoselective allylation of a β-alkoxy aldehyde with 1,3-asymmetric induction and a second stereoselective allylation to prepare the C-glycosidic type of linkage. Use of the Hafner−Duthaler reagent was investigated as a potential means of constructing the anti vicinal hydroxyl−methyl relationships found in the C 19 −C 24 segment but was found not to be practical in this instance. The Evans bis propionate methodology was used to introduce a four-carbon unit, and a Mukaiyama aldol was used for chain extension to incorporate the remaining two carbons and two stereocenters of this segment. Attempted use of the Hanessian benzylidene acetal fragmentation reaction in this sequence was thwarted by neighboring group participation of an oxazolidinone in one case and an unexpected regiochemical outcome in another. The approach developed affords the C 19 −C 35 substructure in 18 steps overall from ethyl acetoacetate and in adequate quantities (10% overall yield) to support the projected total synthesis.",10.1021/jo990291y,1999-05-19,0.6413426504065525
Tetrahedron,A diastereoselective route to (±)-isoretronecanol,,10.1016/0040-4039(81)80132-3,1981-01-01,0.6413303788579284
Organic Letters,"First Total Synthesis of Trimeric Indole Alkaloid, Psychotrimine","The first total synthesis of (+/-)-psychotrimine, a novel trimeric indole alkaloid isolated from Psychotria rostrata, was achieved. In the total synthesis, the copper-mediated intramolecular and intermolecular aminations of halobenzenes, which respectively contributed to the construction of a pyrrolidinoindoline core and the installation of a third tryptamine unit, were used as key steps.",10.1021/ol702637r,2007-12-11,0.6413183521614021
Synlett,Nonchiral-Pool Synthesis of (+)-Hyacinthacine B1,"The first nonchiral-pool total synthesis of (+)-hyacinthacine B1 has been achieved. The synthesis uses as key steps an efficient [2+2] cycloaddition of dichloroketene to a chiral enol ether, two diastereoselective Bruylants-like alkylations, and an effective double Tamao-Fleming oxidation.",10.1055/s-0028-1088147,2009-03-20,0.6413078761177183
Organic Letters,Enantioselective Total Synthesis of the Natural γ-Tocopherol Metabolite (<i>S</i>)-γ-CEHC [(<i>S</i>)-LLU-α],"The asymmetric synthesis of the natural gamma-tocopherol metabolite (S)-gamma-CEHC (1) is described in 10 steps and 18.4% overall yield starting from 2,3-dimethylhydroquinone. The key step is a stereoselective TiCl(4)-mediated homochiral sulfoxide-directed allylation of ketal (SS)-3 to efficiently generate the challenging C-2 stereogenic carbon of chroman (SS,S)-2 with the correct absolute configuration.",10.1021/ol9027804,2010-01-06,0.6413061634814758
Angewandte Chemie International Edition,Inside Cover: Total Synthesis of (±)‐Aspidophylline A (Angew. Chem. Int. Ed. 7/2014),The total synthesis of the monoterpene alkaloid aspidophylline A is described by J. Zhu and et. al. in their Communication on page 1818 ff. The concise synthetic strategy features rapid access to the pentacyclic skeleton of aspidophylline A by using intramolecular Michael additions as key steps. The strategy could potentially provide a feasible route to other congeners of the akuammiline family of alkaloids.,10.1002/anie.201400427,2014-01-30,0.641285232802518
Journal of Organic Chemistry,Total Synthesis of Clerobungin A via a Cascade Cyclization Reaction,"The first total synthesis of the novel cyclohexylethanoid natural product clerobungin A has been achieved in six steps and 14% overall yield starting from commercially available tyrosol. Key steps in this sequence include a bioinspired oxidative dearomatization of a phenol and a hemiacetalization/oxa-Michael cascade to form the tricyclic ring system. Resolution of a late-stage intermediate via chiral HPLC allowed for the measurement of the chiroptical properties of both enantiomers of clerobungin A, supporting the scalemic nature of the natural product.",10.1021/acs.joc.6b02261,2016-11-09,0.6412515756707394
Journal of Organic Chemistry,"Total Syntheses of (+)- and (−)-Cacospongionolide B, Cacospongionolide E, and Related Analogues. Preliminary Study of Structural Features Required for Phospholipase A<sub>2</sub>Inhibition","The total syntheses of the antiinflammatory marine sponge metabolites (+)-cacospongionolide B and E are described. The pivotal steps in the synthetic route include a three-step sequence that couples the two main regions of the natural product, as well as generates the side chain dihydropyran ring. The activity of the synthetic analogues against bee venom phospholipase A2 suggests that the cacospongionolides have enantiospecific interactions with the enzyme that may be independent of the gamma-hydroxybutenolide moiety.",10.1021/jo049285e,2004-07-14,0.6412460958208083
Organic Process Research & Development,An Improved and Scalable Process for the Synthesis of 5-Azacytidine: An Antineoplastic Drug,"An improved, practical, and scalable process for the manufacture of antineoplastic drug, 5-azacytidine ( 1 ), is described. A thorough understanding of the reaction parameters and stability of the reaction intermediates led us to the development of a robust process. The challenges in the isolation and systematic approach used to streamline the process into a very robust and practical manufacturing process are described.",10.1021/op300192e,2013-01-02,0.6412416679116111
Tetrahedron,A general route for the synthesis of flexible porphyrin dimers,,10.1016/s0040-4039(99)01375-1,1999-09-01,0.6412235890502332
Journal of Organic Chemistry,De Novo Synthesis of Aceric Acid and an Aceric Acid Building Block,The de novo synthesis of an aceric acid thioglycoside building block and the total synthesis of the plant carbohydrate aceric acid are described via a highly convergent strategy. Aldol reaction of acetaldehyde and a protected tartaric acid derivative provided the open chain carbohydrate. Subsequent acid treatment yielded the aceric acid thioglycoside in 35% total yield over five steps. Oxidative cleavage of the thioketal in the open chain carbohydrate and basic hydrolysis of the methyl ester furnished fully deprotected aceric acid in 31% yield over six steps.,10.1021/jo061607m,2006-09-19,0.6412194449571019
Organic Letters,Asymmetric Synthesis of Highly Functionalized Tetrahydropyran DPP-4 Inhibitor,"A practical synthesis of a highly functionalized tetrahydropyran DPP-4 inhibitor is described. The asymmetric synthesis relies on three back-to-back Ru-catalyzed reactions. A Ru-catalyzed dynamic kinetic resolution (DKR) reduction establishes two contiguous stereogenic centers in one operation. A unique dihydropyran ring is efficiently constructed through a preferred Ru-catalyzed cycloisomerization. Hydroboration followed by a Ru-catalyzed oxidation affords the desired functionalized pyranone core scaffold. Finally, stereoselective reductive amination and subsequent acidic deprotection afford the desired, potent DPP-4 inhibitor in 25% overall yield.",10.1021/ol502661g,2014-09-30,0.6412181596403932
European Journal of Organic Chemistry,Formal Semisynthesis of Demethylgorgosterol Utilizing a Stereoselective Intermolecular Cyclopropanation Reaction,"Abstract In this study, we report a convenient and high yielding formal semisynthesis of demethylgorgosterol, a marine steroid with an intriguing sidechain containing a cyclopropane unit. This was achieved through the synthesis of an advanced ketone intermediate. The synthetic route features a total of ten steps, starting from commercially available stigmasterol, with an overall yield of 27 %. The key step was a stereoselective intermolecular cyclopropanation reaction. This reaction proceeded in 82 % yield, the resulting cyclopropane carboxylic ester shows a trans/cis ratio of 89 : 11, with a diastereomeric ratio for the trans‐diastereomers of &gt;99 : 1. A reduction/oxidation sequence afforded the corresponding aldehyde, which was used in a Grignard reaction. A final oxidation step then yielded the desired ketone. This novel route presents a platform to further investigate the medicinal applications of gorgosterol‐type steroids and to fully understand their role in coral symbiosis.",10.1002/ejoc.202100035,2021-01-23,0.641206150528615
Organic Letters,"Improved Asymmetric Synthesis of 3,4-Dihydro-2-[3-(1,1,2,2-tetrafluoroethoxy)phenyl]-5-[3-(trifluoromethoxy)phenyl]-α-(trifluoromethyl)-1(2<i>H</i>)-quinolineethanol, a Potent Cholesteryl Ester Transfer Protein Inhibitor","The asymmetric synthesis of 3,4-dihydro-2-[3-(1,1,2,2-tetrafluoroethoxy)phenyl]-5-[3-(trifluoromethoxy)phenyl]-alpha-(trifluoromethyl)-1(2H)-quinolineethanol (compound 11), a cholesteryl ester transfer protein inhibitor, is accomplished. The asymmetric center is established via the chiral reduction of ketone 4 employing Corey's (R)-Me CBS oxazaborolidine reagent. The tetrahydroquinoline core of the molecule is established via a Cu-mediated intramolecular amination reaction. The preparation of the prochiral ketone 4 has also been improved by eliminating the use of a hazardous aryltin reagent.",10.1021/ol900639j,2009-06-09,0.6411713423142874
Tetrahedron,The synthesis of methyl isomarasmate,,10.1016/0040-4039(70)80081-8,1970-01-01,0.6411654435722868
Tetrahedron,"Synthesis of quinonoid 6-methyl- and 6,7-dimethyldihydropterins 1",,10.1016/s0040-4039(00)98709-4,1985-01-01,0.6411654435722868
Tetrahedron,Synthesis of 2-(methoxycarbonyl)methyl-7-phenylacetamido-3-thiacepham-4-carboxylates,,10.1016/s0040-4039(00)84243-4,1986-01-01,0.6411654435722868
Tetrahedron,"The synthesis of 1-methyl-2:3,6:7-dibenzo-1,4, 5-triaza-cyclohepta-2,6-diene",,10.1016/s0040-4039(01)82744-1,1959-01-01,0.6411654435722868
Tetrahedron,"Synthesis of (2,4,6-cycloheptatrien-1-ylidene)methyl triphenylphosphonium tetrafluoroborate: a strongly stabilized ylide ?",,10.1016/s0040-4039(00)92599-1,1980-01-01,0.6411654435722868
Tetrahedron,"Latent acetonylation of α,β -enones with allyltrimethylsilane or 2-methyl-2-propenyltrimethylsilane: synthesis of 1,5-diketones and annelation to fused cyclohexenones",,10.1016/s0040-4039(00)77749-5,1980-01-01,0.6411654435722868
Tetrahedron,"Synthesis of methyl (5Z,8Z,10E,12E,14Z)-eicosapentaenoate",,10.1016/j.tetlet.2010.12.078,2011-01-08,0.6411654435722868
Tetrahedron,A synthesis of 6-methyl-2′-deoxyuridine,,10.1016/s0040-4039(01)95781-8,1973-01-01,0.6411654435722868
Tetrahedron,First synthesis of methyl α-C-d-arabinofuranosyl-(1→5)-α-d-arabinofuranoside: the C-disaccharide segment of motif C of Mycobacterium tuberculosis,,10.1016/s0040-4039(02)01760-4,2002-10-01,0.6411654435722868
Tetrahedron,"Synthesis of 2-methyl-1,3-cyclopentanedione monoethylene ketal",,10.1016/s0040-4039(00)84660-2,1986-01-01,0.6411654435722868
Tetrahedron,Sexual hormones of Mucorales. The synthesis of methyl trisporate B and C,,10.1016/0040-4039(71)80003-5,1971-01-01,0.6411654435722868
Tetrahedron,"Cyclopentenones from 2-ethoxyallylidene(triphenyl)phosphorane and 1,2-diacylethylenes: Synthesis of (±)-methyl dehydrojasmonate",,10.1016/0040-4039(95)00515-e,1995-05-01,0.6411654435722868
Tetrahedron,R-3-methyl-γ-butyrolactone as a template for the synthesis of (+)-invictolide,,10.1016/s0040-4039(00)84224-0,1986-01-01,0.6411654435722868
Tetrahedron,"Biomimetic synthesis of the neolignans kadsurenone, denudatin B, O-methyl-liliflodione, and liliflol B",,10.1016/s0040-4039(99)01063-1,1999-07-01,0.6411654435722868
Tetrahedron,"Synthesis of methyl 6-aralkl-2,5-diketopiperidine-3-carboxylates as synthons of conformationally constrained pseudopeptides",,10.1016/0040-4039(91)80834-s,1991-07-01,0.6411654435722868
Tetrahedron,"Synthesis of 2-acetamido-2-deoxy-α-D-glycosyl phosphates 2-methyl-glyco[2′,1′:4,5]-2-oxazolines",,10.1016/s0040-4039(00)89350-8,1970-01-01,0.6411654435722868
Synthesis,"Synthesis of 2-Formyl-6-methyl-7β-hydroxybicyclo-[4.3.0]nona-2,9-diene",,10.1055/s-1976-24023,1976-01-01,0.6411654435722868
Synthesis,Synthesis of 2-Aryliminoimidazolidines and 2-Arylaminobenzimidazoles from Methyl<i>N</i>-Aryldithiocarbamates,,10.1055/s-1982-29846,1982-01-01,0.6411654435722868
Synthesis,"Synthesis of 1-Methyl-3,4-dihydropyrido[1,2-<i>a</i>]benzimidazoles",,10.1055/s-1978-24778,1978-01-01,0.6411654435722868
Tetrahedron,An expeditious synthesis of 3′-α-carboxymethyl-2′-O-methyl ribonucleosides,,10.1016/s0040-4039(99)00147-1,1999-03-01,0.6411654435722868
Tetrahedron,"Synthesis of methyl 4-dihydrotrisporate B, a prohormone of",,10.1016/s0040-4039(00)94515-5,1983-01-01,0.6411654435722868
Tetrahedron,A synthesis of methyl D-aldgaroside B,,10.1016/s0040-4039(01)91803-9,1974-01-01,0.6411654435722868
Tetrahedron,"Synthesis of (2s,3r,4e,8e)-n-(2′r)-2′-hydroxyhexadecanoyl-9-methyl-4,8-sphingadienine, the ceramide portion of the fruiting-inducing cerebroside in a basidiomycete schizophyllum commune",,10.1016/s0040-4039(01)81586-0,1984-01-01,0.6411654435722868
Tetrahedron,Synthesis of methyl α-caryophylloside,,10.1016/s0040-4039(99)02039-0,2000-01-01,0.6411654435722868
Synthesis,"An Expeditious Synthesis of Methyl 2,6-Dideoxy-α-D-<i>arabino</i>-hexopyranoside",,10.1055/s-1980-29315,1980-01-01,0.6411654435722868
Organic Letters,Synthetic Studies on the Bryostatins:  Preparation of a Truncated BC-Ring Intermediate by Pyran Annulation,"[reaction: see text]. A synthesis of a potential BC-ring subunit (C9-C27) for bryostatin 1, a remarkably potent anticancer agent, has been developed in 16 steps and 18% overall yield. The key features of this route include a BITIP-catalyzed asymmetric allylation reaction, chelation-controlled allylations, a hydroformylation reaction, and a pyran annulation reaction.",10.1021/ol050511w,2005-04-28,0.6411600310870199
Journal of Organic Chemistry,"Synthesis of the Pheromone of the Longtailed Mealybug, a Sterically Congested, Irregular Monoterpenoid","A straightforward and scaleable synthesis of the sterically congested pheromone of the longtailed mealybug, with two adjacent quarternary carbons in a cyclopentene ring, was accomplished in 13.5% overall yield. Key steps included regiospecific cyclization of an alpha-diazo-beta-ketoester to build the cyclopentane ring, followed by reduction of the enol triflate of the ketone to place the double bond.",10.1021/jo901505y,2009-08-18,0.641157846509924
Organic Letters,"Formal Synthesis of Palmerolide A, Featuring Alkynogenic Fragmentation and <i>syn</i>-Selective Vinylogous Aldol Chemistry","An enantioselective route to palmerolide A is described. The approach features original syntheses of three subunits, which are then assembled to produce a known late-stage intermediate and formally provide the highest overall yield of the natural product reported to date. Recent innovations in alkynogenic fragmentation and vinylogous aldol methodology figure prominently in the synthesis of the C1-C15 and C16-C25 subunits, respectively.",10.1021/ol400014e,2013-02-01,0.6411481143918274
Journal of the American Chemical Society,Total Synthesis of Tetrahydrolipstatin and Stereoisomers via a Highly Regio- and Diastereoselective Carbonylation of Epoxyhomoallylic Alcohols,A concise enantioselective synthesis of tetrahydrolipstatin (THL) and seven stereoisomers has been achieved. The synthesis of THL was accomplished in 10 steps and 31% overall yield from an achiral ynone. Key to the success of the approach is the use of a bimetallic [Lewis acid](+)[Co(CO)4](-) catalyst for a late-stage regioselective carbonylation of an enantiomerically pure cis-epoxide to a trans-β-lactone. The success of this route to THL and its stereoisomers also demonstrated the practicality of the carbonylation catalyst for complex molecule synthesis as well as its functional group compatibility.,10.1021/ja505639u,2014-07-08,0.6411411569728995
Organic Letters,An Expedient Enantioselective Strategy for the Oxatetracyclic Core of Platensimycin,An enantioselective route for the synthesis of oxatetracyclic core of platensimycin is reported for the first time using a 5-exo-trig cyclization followed by intramolecular etherification as key reactions. The requisite dienynone for the radical cyclization is synthesized in eight steps from the Wieland-Miescher ketone employing a Claisen rearrangement.,10.1021/ol070848t,2007-05-10,0.6410995013947078
Synthesis,A Rapid and Efficient Synthesis of 2-Butyl-5-Chloro-3<i>H</i>-Imidazole-4-Carboxaldehyde,"A rapid, efficient, cost effective procedure has been developed for the synthesis of 2-butyl-5-chloro-3H-imidazole-4-carboxaldehyde. Preparation of methyl pentanimidate was accomplished in just 12 hours, followed by a sequence of reactions without isolation and purification of the formed intermediates. The final compound was purified by simple acid-base treatment to get a product with 99.9% HPLC purity.",10.1055/s-2004-815961,2004-01-01,0.6410975867074726
Synlett,An Asymmetric Synthetic Route to (+)-Lactacystin,"All articles of this category Trihydroxy pyrrolidinone 16 , a key intermediate to (+)-lactacystin 1 , has been stereoselectively synthesized via the highly diastereoselective crotylboration of aldehyde 5 and intramolecular mercurioamidation of allylic trichloroacetimidate 12 to introduce the three requisite contiguous chiral centers of methyl, hydroxy and amino substituents. (+)-lactacystin - neurotrophic activity - crotylboration - trichloroacetimidate - mercurioamidation",10.1055/s-1998-1892,1998-10-01,0.6410865814227775
Tetrahedron,"New route to the synthesis of the indolo[7,6-g]indole (“bis(pyrrolo)naphthalene”) system starting from 1,5-dihydroxynaphthalene",,10.1016/s0040-4039(99)00121-5,1999-03-01,0.6410795768371597
Synthesis,A Convenient Synthesis of Hispidin from Piperonal,(opens in new window) Buy Article (opens in new window) Permissions and Reprints (opens in new window) All articles of this category (opens in new window) An improved synthesis of hispidin (overall yield 24%) starting from the commercially available piperonal is reported. This three-step method is more effective and advantageous compared to the known six-step preparation.,10.1055/s-1994-25654,1994-01-01,0.641074750868672
Organic Letters,Cata-Condensed Heteroannulated Coronenes via Selective Bromination of Diarenoperylenes as the Key Step,A facile three-step synthetic route to heteroannulated extended coronenes via a selective bromination of diarenoperylenes as the key step is presented. The heteroannulated coronenes were characterized by X-ray crystallography and by photophysical and electrochemical means.,10.1021/acs.orglett.8b03181,2018-11-05,0.6410693414692629
Organic Process Research & Development,Process Development of Tacalcitol,"A highly convergent, gram-scale synthesis of vitamin D3 analogue tacalcitol 1 is disclosed, starting from L -valine and Inhoffen–Lythgoe diol. Key features of the synthesis include modified Julia olefination reaction of β-oxybenzothiazol-2-yl sulfone with C/D ring containing aldehyde to access decagrams of fully functionalized C/D ring synthon. The Horner–Wadsworth–Emmons (HWE) reaction between the C/D ring fragment and commercially available phosphonate completes the carbo-skeleton, which is elaborated into tacalcitol 1 in a gram-scale synthesis.",10.1021/acs.oprd.1c00010,2021-02-23,0.6410381195151768
Journal of Organic Chemistry,Ti(III)-Promoted Radical Cyclization of Epoxy Enones. Total Synthesis of (+)-Paeonisuffrone,"The total synthesis of (+)-paeonisuffrone starting from (+)-10-hydroxycarvone is described. The key step of our synthetic strategy is a titanium-catalyzed stereoselective cyclization initiated by epoxide opening through electron transfer. This reaction stereoselectively affords the highly oxygenated pinane skeleton present in the target molecule and opens a new and effective approach to the synthesis of the complex, biologically active terpenoids isolated from the roots of the Chinese paeony (Paeonia albiflora Pallas and Paeonia suffruticosa Andrews).",10.1021/jo8026033,2009-01-20,0.6410367349533035
Synlett,Enantioselective Total Synthesis of Marine Natural Products Untenone A and Plakevulin A,"An enantioselective total synthesis of untenone A and plakevulin A has been achieved. Construction of a cyclopentene ­derivative, the key intermediate in this synthesis, was carried out by using a ruthenium-catalyzed ring-closing metathesis reaction of a divinyl compound, prepared from octadecanal in several steps including the Sharpless asymmetric epoxidation to generate a chiral quaternary carbon center.",10.1055/s-2005-863742,2005-01-01,0.6410341220154545
Synthesis,Formal Synthesis of (-)-Frontalin through Diastereoselective Hydrocyanation of a β-Keto Sulfoxide,"The diastereoselective synthesis of (S)-4-(2,2,4-trimethyl-1,3-dioxolan-4-yl)butan-1-ol (9), an intermediate in the asymmetric synthesis of the pine beetle pheromone (-)-frontalin [(1S,5R)-1,5-dimethyl-6,8-dioxabicyclo[3.2.1]octane] (1), has been accomplished starting from the β-keto sulfoxide 2, derived from glutaric anhydride. The key step of the synthetic sequence is the diastereoselective hydrocyanation of 2 by diethylaluminum cyanide.",10.1055/s-2008-1067120,2008-06-11,0.6410277521119053
Organic Letters,Total Synthesis of the Microtubule-Stabilizing Agent (−)-Laulimalide,"[structure: see text] The total synthesis of the potent microtubule-stabilizing anticancer agent (-)-laulimalide has been achieved in 27 steps and 2.9% overall yield. Notable features are the use of Jacobsen HDA chemistry for the enantioselective construction of the side chain dihydropyran, a diastereoselective aldol coupling using chiral boron enolate methodology, a Mitsunobu macrolactonization, and a Sharpless AE to introduce the epoxide onto des-epoxy-laulimalide.",10.1021/ol010150u,2001-09-06,0.6410182272753293
Journal of Organic Chemistry,Stereoselective Synthesis of a Key Precursor of Halicholactone and Neohalicholactone,"An efficient synthesis of a known precursor of halicholactone (1a) and neohalicholactone (1b) has been developed using the strategically functionalized key cyclopropane intermediate 2, which in turn has been synthesized via stereoselective cyclopropanation of trans-cinnamyl alcohol in the presence of the chiral dioxaborolane ligand 4. Elaboration of the above bifunctional cyclopropane to the target molecule was achieved in a relatively short reaction sequence and in good overall yield, representing a formal synthesis of the title compounds.",10.1021/jo971564x,1998-01-09,0.6410151411150129
Journal of Organic Chemistry,Synthesis of Macrocyclic Peptide Analogues of Proteasome Inhibitor TMC-95A,"The synthesis of three constrained macrocyclic peptide analogues 1 of TMC-95A as potential proteasome inhibitors is described. The key step involves a Ni(0)-mediated macrocyclization of tripeptides 2 bearing halogenated aromatic side chains for the formation of the biaryl junction. In addition, an enantioselective preparation of l-7-bromotryptophan methyl ester 3 using a Corey-O'Donnell alkylation of the glycine benzophenone imine was achieved in good overall yield with very high ee (>85%) on a multigram scale.",10.1021/jo035256c,2003-11-11,0.640985422310966
Journal of the American Chemical Society,Biomimetic Entry to the Sarpagan Family of Indole Alkaloids:  Total Synthesis of (+)-Geissoschizine and (+)-<i>N</i>-Methylvellosimine,"A concise synthesis of (+)-geissoschizine (1), a biosynthetic precursor of a variety of monoterpenoid indole alkaloids, from d-tryptophan (19) was performed as a critical prelude to achieving the first biomimetic, enantioselective synthesis of the sarpagine alkaloid (+)-N(a)-methylvellosimine (5). The approach to (+)-geissoschizine was designed to address the dual problems of stereocontrolled formation of the E-ethylidene moiety and the correct relative configuration at C(3) and C(15). Key steps in the synthesis involve a vinylogous Mannich reaction to prepare the carboline 22, which has the absolute stereochemistry at C(3) corresponding to that in 1 and 5, and an intramolecular Michael addition that leads to the tetracyclic corynantheane derivative 24, which possesses the correct stereochemical relationship between C(3) and C(15). Compound 24 was then transformed into 27, the pivotal intermediate in the syntheses of 1 and 5, by a sequence that allowed the stereospecific introduction of the E-ethylidene moiety. Selective reduction of the lactam in 27 followed by removal of the C(5) carboxyl group by radical decarbonylation gave deformylgeissoschizine (2) that was converted into (+)-geissoschizine (1) by formylation. The common intermediate 27 was then converted via a straightforward sequence of reactions into the alpha-amino nitrile 39. The derived silyl enol ether 40 underwent ionization upon exposure to BF(3).OEt(2) to give the intermediate iminium ion 41 that then cyclized in a biomimetically inspired intramolecular Mannich reaction to deliver (+)-N(a)-methylvellosimine (5). This transformation provides experimental support for the involvement of such a cyclization as one of the key steps in the biosynthesis of the sarpagine and ajmaline alkaloids.",10.1021/ja0296024,2003-03-20,0.6409541135971351
Synthesis,Synthesis of Lacosamide (Vimpat) and Its Derivatives from Aziridine-(2R)-carboxylate,"An efficient and scalable synthesis of the antiepileptic drug ( R )-lacosamide and its derivatives has been achieved from commercially available aziridine-(2 R )-carboxylate in three simple sequential steps, including regioselective aziridine ring opening, debenzylation followed by acetylation in one pot, and amide formation. The advantage of this protocol is that the starting material and reagents are commercially available and a single purification by recrystallization is required after all the chemical transformations, providing the final drug in >99.9% ee.",10.1055/s-0036-1588093,2016-11-23,0.6409150166661723
Journal of Organic Chemistry,"Enantiospecific Total Synthesis of the Important Biogenetic Intermediates along the Ajmaline Pathway, (+)-Polyneuridine and (+)-Polyneuridine Aldehyde, as well as 16-Epivellosimine and Macusine A","The first stereospecific synthesis of polyneuridine aldehyde (6), 16-epivellosimine (7), (+)-polyneuridine (8), and (+)-macusine A (9) has been accomplished from commercially available d-(+)-tryptophan methyl ester. d-(+)-Tryptophan has served here both as the chiral auxiliary and the starting material for the synthesis of the common intermediate, (+)-vellosimine (13). This alkaloid was available in enantiospecific fashion in seven reaction vessels in 27% overall yield from d-(+)-trytophan methyl ester (14) via a combination of the asymmetric Pictet-Spengler reaction, Dieckmann cyclization, and a stereocontrolled intramolecular enolate-driven palladium-mediated cross-coupling reaction. A new process for this stereocontrolled intramolecular cross-coupling has been developed via a copper-mediated process. The initial results of this investigation indicated that an enolate-driven palladium-mediated cross-coupling reaction can be accomplished by a copper-mediated process which is less expensive and much easier to work up. An enantiospecific total synthesis of (+)-polyneuridine aldehyde (6), which has been proposed as an important biogenetic intermediate in the biosynthesis of quebrachidine (2), was then accomplished in an overall yield of 14.1% in 13 reaction vessels from d-(+)-tryptophan methyl ester (14). Aldehyde 13 was protected as the N(a)-Boc aldehyde 32 and then converted into the prochiral C(16)-quaternary diol 12 via the practical Tollens' reaction and deprotection. The DDQ-mediated oxidative cyclization and TFA/Et(3)SiH reductive cleavage served as protection/deprotection steps to provide a versatile entry into the three alkaloids polyneuridine aldehyde (6), polyneuridine (8), and macusine A (9) from the quarternary diol 12. The oxidation of the 16-hydroxymethyl group present in the axial position was achieved with the Corey-Kim reagent to provide the desired beta-axial aldehydes, polyneuridine aldehyde (6), and 16-epivellosimine (7) with 100% diastereoselectivity.",10.1021/jo100279w,2010-04-14,0.6409149636266572
European Journal of Organic Chemistry,The Formal Total Synthesis of FR252921 – An Immunosuppressant,"Abstract The formal total synthesis of FR252921 is described. The key steps include the preparation of three fragments starting from 1,4‐butanediol, ( R )‐malic acid, and prenol, respectively, followed by two consecutive peptide couplings of the three fragments. Other key steps involve an allene‐type rearrangement or enyne isomerization to install the triene moiety, a Seebach methylation, a Julia olefination to construct the trisubstituted diene unit, and an enzymatic resolution strategy to generate the C‐18 stereocenter.",10.1002/ejoc.201201097,2012-11-15,0.6408856751167712
Organic Letters,Asymmetric Total Synthesis of Alkaloids 223A and 6-<i>epi</i>-223A,"Concise and asymmetric total synthesis of the title compounds are described. The key ring system was constructed using an intramolecular Schmidt reaction on a norbornenone derivative, which was subsequently subjected to ring-opening metathesis followed by reduction. An unusual isomerization of the C-6 ethyl group afforded the desired stereochemistry of the natural product. The synthesis is readily adaptable to analogue production.",10.1021/ol901645j,2009-08-19,0.6408793436166647
Journal of Organic Chemistry,A General Synthetic Route to Enantiopure 5-Substituted <i>cis</i>-Decahydroquinolines,"A practical synthetic route to enantiopure 5-substituted cis-decahydroquinolines has been developed, the key steps being a stereoselective cyclocondensation of 2-substituted 6-oxocyclohexenepropionates 2 with (R)-phenylglycinol, the stereoselective hydrogenation of the resulting unsaturated tricyclic lactams, and the stereoselective reductive cleavage of the oxazolidine ring.",10.1021/jo802587h,2009-01-02,0.6408632772813533
Synlett,A Formal Total Synthesis of(-)-Dysiherbaine,A key intermediate hexahydrofuropyran 2 to (-)-dysiherbaine 1 has been synthesized concisely via intramolecular oxymercuration and iodocyclization to install the asymmetric centers at the ring junction and the amino group in the tetrahydropyran stereoselectively.,10.1055/s-2003-39318,2003-01-01,0.6408556854212754
Synlett,A Facile and Efficient Asymmetric Synthesis of Florfenicol,"A facile and efficient enantioselective synthesis of flor­fenicol starting from commercially available 4-methylthiobenzaldehyde is described. Key features of the synthesis include a one-step oxidation of allyl and thioether groups in allylic alcohol to form (2S,3S)-epoxide under Sharpless epoxidation conditions and a highly efficient conversion of (1R,2R)-azide into amino alcohol via debenzylation and reduction of an azido moiety in one-pot operation.",10.1055/s-0031-1289858,2011-11-09,0.6408428965548729
Organic Letters,Asymmetric Total Syntheses of <i>ent</i>-Stachybotrin C and Its Congener,"-stachybotrin C and its congener have been accomplished through a convergent approach in the longest linear sequence of 12 steps from commercially available materials, respectively. Noteworthy transformation of the synthesis involved a cascade Knoevenagel condensation/Hantzsch ester reduction/epoxide ring-opening/transetherification to construct the core pyran ring with two adjacent stereocenters.",10.1021/acs.orglett.4c00380,2024-04-01,0.6408346086651704
Organic Letters,Total Synthesis of the Marine Alkaloid Mansouramycin D,"Mansouramycin D, a cytotoxic alkaloid was isolated from a marine Streptomyces sp. in 2009. The first, simple, and concise route to the total synthesis of Mansouramycin D is reported. The core structure of the isoquinoline ring has been constructed from iminoannulation of 2-alkynylbenzaldehyde followed by oxidation/deprotection and oxidative amination via a three-step sequence from easily accessible starting materials.",10.1021/ol4032396,2013-12-09,0.6408297425255474
Tetrahedron,"A mild and efficient palladium-catalyzed homocoupling of lithium alkynyltriisopropoxyborates: a new route to synthesis of 1,3-diynes",,10.1016/j.tetlet.2004.05.033,2004-06-01,0.6408287265396486
Organic Process Research & Development,An Improved Scalable Route to Pure Dronedarone Hydrochloride,"An efficient scalable synthesis for dronedarone hydrochloride ( 2 ) via Friedel–Craft acylation of 2-(-2-butyl-1-benzofuran-5-yl)-1 H -isoindole-1,3(2 H )dione ( 12 ) with 4-(3-chloropropoxy) benzoic acid ( 13 ) in good yield and high purity has been developed by using Eaton’s reagent instead of hazardous and toxic metal halide catalyst like AlCl 3 or SnCl 4 .",10.1021/op300017v,2012-03-06,0.6408268298805903
Journal of Organic Chemistry,Furan Oxidation Strategy for the Synthesis of the Macrolactone Analogue of Migrastatin,"Synthesis of the 14-membered macrolide core of migrastatin is accomplished by the use of furyl carbinol in 13 linear steps from furfural with ∼11% overall yield. Key strategies in the synthesis include the oxidative ring opening of furan and its use as a four-carbon synthon, S N 2 displacement of a functionalized allyl bromide, and ring closing metathesis to obtain the macrolactone.",10.1021/acs.joc.9b02413,2019-10-16,0.6408158757296909
European Journal of Organic Chemistry,An Enantioselective Approach to Pinguisane Sesquiterpenes: Total Synthesis of (–)‐Pinguisenol and (–)‐Isonaviculol,"A short and efficient enantioselective approach to pinguisane‐type sesquiterpenes has been developed starting from a Hajos–Parrish‐type ketone. This led to the first total syntheses of isonaviculol (10 steps, 6.6 % overall yield) and natural pinguisenol (9 steps, 12 % overall yield). The key reactions were regioselective thioketal protection, stereoselective cyclopropanation using Furukawa's protocol, diastereoselective hydrogenation of an olefin using a Thalesnano H‐Cube Pro flow reactor, Li/liquid NH 3 mediated cyclopropane reduction, and a PCC‐mediated 1,3‐oxidative transposition sequence.",10.1002/ejoc.201700395,2017-05-06,0.6408116297706478
Tetrahedron,"Total synthesis of PI-201, a new platelet aggregation inhibitor : Establishment of its absolute stereochemistry",,10.1016/s0040-4039(00)79308-7,1993-11-01,0.6408099517580678
Tetrahedron,Total synthesis of (±)-4-deoxyverrucarol; a new route to trichothecanes via ring expansion of small ring compounds,,10.1016/s0040-4039(99)00047-7,1999-03-01,0.6408082512923736
Tetrahedron,"A versatile route for the synthesis of 3-(1′, 1′-dimethyllallyl)coumarins",,10.1016/s0040-4039(00)87257-3,1982-01-01,0.6407953085572741
European Journal of Organic Chemistry,"A Short Synthesis of (−)‐6,7‐Secoagroclavine via Metal‐Free Reductive Coupling","Abstract A concise, convergent, and enantioselective synthesis of (−)‐6,7‐secoagroclavine, a pivotal intermediate in the synthesis of both clavine and ergot alkaloids, was accomplished from a derivative of the renowned Uhle's ketone. The synthesis is centered on metal‐free reductive coupling of the tosylhydrazone derivative of protected 4‐amino Uhle's ketone and commercially available 2,2‐dimethylethenylboronic acid, which is used as a four‐carbon building block. This novel approach directly sets the stereochemistry on the difficult‐to‐access aryl vinyl methane carbon stereogenic center of (−)‐6,7‐secoagroclavine.",10.1002/ejoc.202400035,2024-02-16,0.6407885236103806
Journal of the American Chemical Society,Total Synthesis of (+)-Prelaureatin and (+)-Laurallene,The first total syntheses of (+)-prelaureatin and (+)-laurallene are described. An asymmetric glycolate aldol addition was followed by a ring-closing metathesis to close the eight-membered ring allowing construction of the oxocene core of (+)-prelaureatin and (+)-laurallene in seven synthetic steps from ( R )-benzylglycidyl ether.,10.1021/ja0007197,2000-05-26,0.6407863798886526
European Journal of Organic Chemistry,First Total Synthesis of the Pyrrolizidine Alkaloid Amphorogynine C through Intramolecular Azide–Olefin Cycloaddition,"Abstract The first total synthesis of the natural alkaloid amphorogynine C is reported (2.9 % overall yield in 20 steps). The key steps include a Claisen–Johnson rearrangement and an intramolecular azide–olefin cycloaddition, followed by a reduction of the resulting imine. The construction of the pyrrolizidine skeleton was achieved by an alkoxide‐mediatedlactone ring opening and subsequent cyclization of a conveniently functionalized bicyclic amine. Finally, the proposed structure of amphorogynine C was confirmed by single‐crystal X‐ray diffraction analysis.",10.1002/ejoc.201200384,2012-06-27,0.6407810351853513
European Journal of Organic Chemistry,Cesium Carbonate‐Mediated Cascade Cyclization for the Efficient Synthesis of Fused Benzo[ <i>b</i> ]naphthooxepinone Derivatives,"An efficient base‐promoted synthetic approach has been developed for the synthesis of benzo[ b ]naphthooxepinones from (3‐(acetylphenoxy)prop‐1‐yn‐1‐yl)benzaldehydes. The transformation proceeds via a base‐mediated 7‐ exo‐dig cyclization, followed by intramolecular aldol condensation and subsequent dehydration, resulting in the formation of a fused tricyclic ring system. This one‐pot protocol affords a series of benzo[ b ]naphthooxepinone derivatives in moderate to good yields, offering a concise and environmentally benign route to these polycyclic scaffolds.",10.1002/ejoc.202500862,2025-11-17,0.6407515295877354
Tetrahedron,"Total synthesis of a new inhibitor of superoxide anion generation, opc-15161",,10.1016/s0040-4039(00)79453-6,1991-10-01,0.6407352681485524
Synthesis,Asymmetric Formal Synthesis of (+)-Pyrenolide D,"A concise, asymmetric formal synthesis of (+)-pyrenolide D from ( E )-crotonaldehyde is described. The key steps include an enantioselective Sharpless dihydroxylation of protected hex-4-en-1-yn-3-ol and a highly diastereoselective palladium-catalysed oxycarbonylation of (2 R ,3 S ,4 S )-hex-5-ene-2,3,4-triol using iron pentacarbonyl as the carbon monoxide source.",10.1055/s-0033-1338584,2014-01-23,0.6407236538554413
Tetrahedron,A new asymmetric synthesis of (+)-12b-epidevinylantirhine,,10.1016/j.tetlet.2006.06.033,2006-07-08,0.640710249140595
Journal of the American Chemical Society,Total Synthesis of (+)-Isolaurepinnacin. Use of Acetal-Alkene Cyclizations To Prepare Highly Functionalized Seven-Membered Cyclic Ethers,"The first synthesis of the title compound is described. The synthesis features an acetal-vinylsilane cyclization to stereoselectively form the cis -2,7-disubstituted oxepene ring and introduce Δ 4 unsaturation. Starting with (2 R,3 S )-2,3-epoxypentan-1-ol ( 16 ), mixed acetal 10 is formed in five steps and 72% overall yield. Treatment of 10 with excess BCl 3 in CH 2 Cl 2 at −78 → 0 °C promotes cyclization to afford Δ 4 -oxepene 39 in 90% yield after deprotection of the silyl ether. Elaboration of the ( E )-enyne functionality of the six-carbon side chain completes the synthesis of (+)-isolaurepinnacin.",10.1021/ja964080b,1997-03-01,0.6407085953799275
Journal of the American Chemical Society,Total Synthesis of (−)-Nodulisporic Acid D,"A convergent total synthesis of the architecturally complex indole diterpenoid (-)-nodulisporic acid D has been achieved. Key synthetic transformations include vicinal difunctionalization of an advanced α,β-unsaturated aldehyde to form the E,F-trans-fused 5,6-ring system of the eastern hemisphere and a cascade cross-coupling/indolization protocol leading to the CDE multisubstituted indole core.",10.1021/jacs.5b04728,2015-06-01,0.6406760646927355
Synlett,Expedient Synthesis of the Proposed Structure of Cryptoconcatone H Exploiting Hidden Symmetry,"Abstract Synthesis of the originally assigned structure of the styryl tetrahydropyranol-dihydropyranone natural product cryptoconcatone H from C 2-symmetric (±)-1,8-nonadiene-4,6-diol is reported. Desymmetrization by Mitsunobu reaction with crotonic acid established the requisite inter-ring stereochemical relationship and was followed by a highly diastereoselective Re2O7-catalyzed Prins cyclization with cinnamaldehyde to construct the 2,4,6-cis-tetrahydropyranol ring. Ring-closing metathesis resulted in formation of the dihydropyranone ring and completed the synthesis in three steps and 32% overall yield. The brevity of the synthesis is the result of the recognition of hidden, inter-ring symmetry in the target and the ensuing choice of an appropriately symmetric diol as our starting material.",10.1055/a-1972-3587,2022-11-04,0.6406642816602969
Synthesis,"New Procedure for the Preparation of (1R,2R)-2-[(R)-3-(Benzyloxy)pyrrolidin-1-yl]cyclohexanol","A novel route to an intermediate of vernakalant, (1R,2R)-2-[(R)-3-(benzyloxy)pyrrolidin-1-yl]cyclohexanol from ethyl (R)-4-chloro-3-hydroxybutanoate is described. It was found that the key intermediate (R)-4-(benzyloxy)-1-[(1R,2R)-2-(tert-butyldimethylsiloxy)cyclohexyl]pyrrolidin-2-one could be isolated with high dia­stereomeric excess (up to 99% de) from its isomer by column chromatography alone, without further chemical resolution.",10.1055/s-0031-1289619,2011-11-23,0.6406617020962224
Organic Process Research & Development,"First, Second, and Third Generation Scalable Syntheses of Two Potent H<sub>3</sub> Antagonists","Our teams have recently completed scale-up campaigns for two structurally similar H 3 receptor antagonists. The first and second generation processes were developed for the synthesis of 107 and 125 g batches of (4-cyclobutyl-1,4-diazepan-1-yl)(6-(4-fluorophenoxy)pyridin-3-yl)methanone·HCl ( 1·HCl ). A third generation process was utilized for production of 104 g of 3-((5-(4-cyclobutyl-1,4-diazepane-1-carbonyl)pyridin-2-yl)oxy)benzonitrile·HCl ( 2·HCl ). The evolution from first to second generation process was driven by a desire to minimize cost of goods through employment of symmetrical homopiperazine rather than a more expensive monoprotected variant. Project demands for a late stage intermediate that could provide 1 or 2 led to additional route scouting and the ultimate determination of a third scalable synthesis for these types of molecules. The use of a lithium alkoxide for Lewis base catalysis of an ester to amide transformation represents a key improvement for the third generation synthesis.",10.1021/op200005e,2011-03-12,0.6406497047074547
Angewandte Chemie International Edition,Total Synthesis of Schilancitrilactones B and C,"The first total syntheses of schilancitrilactones B and C have been accomplished in 17 steps (longest linear sequence) from commercially available materials. Key steps include an intramolecular radical cyclization to provide the seven-membered ring, late-stage iodination, and an intermolecular radical addition reaction to complete the total synthesis.",10.1002/anie.201501169,2015-03-13,0.640637845413469
Organic Letters,An Efficient Total Synthesis of (−)-Epothilone B,"An efficient total synthesis of (-)-epothilone B has been achieved in ca. 8% yield over 11 steps from 9 (or 10 steps from 7/8), which features a bissiloxane-tethered ring closing metathesis reaction to approach the trisubstituted (Z) double bond and forms a new basis for further development of an industrial process for epothilone B and ixabepilone.",10.1021/ol303148g,2012-12-07,0.6406352025396063
Organic Letters,Total Synthesis of Archazolid F,"A partial bioinspired as well as the total synthesis of archazolid F, a highly potent V-ATPase inhibitory, antiproliferative polyketide macrolide, is described. Key features of the synthetic routes include a highly stereoselective aldol condensation of two elaborate fragments and macrocyclizations either by a Shiina macrolactonization or by a challenging RCM reaction of an octaene substrate. The syntheses unequivocally confirm the full architecture of this very scarce archazolid.",10.1021/acs.orglett.8b03715,2018-12-14,0.6406257791061344
Angewandte Chemie International Edition,Synthesis of (±)‐Merrilactone A and (±)‐Anislactone A,A concise synthesis of each of the sesquiterpenoids merrilactone A and anislactone A is described using a common route. Reductive cleavage of an epoxide using TiIII and radical cyclization is used to install the C9 quaternary center at the heart of the BC bicycle (see scheme). Selective lactonization sequences then define regiodivergent pathways to both merrilactone A (formal synthesis) and anislactone A (total synthesis).,10.1002/anie.201005156,2010-10-21,0.6406256850408825
Journal of the American Chemical Society,Total Synthesis of (+)-Complanadine A Using an Iridium-Catalyzed Pyridine C−H Functionalization,"The total synthesis of the Lycopodium alkaloid complanadine A, which is an unsymmetrical dimer of lycodine, was achieved by exploiting a common tetracyclic precursor. Key to the success of the synthesis was the development of a late-stage site-selective C-H functionalization of a pyridine moiety to arrive at a key boronic ester intermediate.",10.1021/ja101893b,2010-04-13,0.6406245307213245
Journal of the American Chemical Society,Highly Convergent Total Synthesis of (+)-Acutiphycin,"An enantioselective, convergent, total synthesis of (+)-acutiphycin (18 steps, longest linear sequence from commercial materials) features the first application of an alkynyl ether as a macrolactone precursor in total synthesis, as well as the first example of an intermolecular, SmI2-mediated, Reformatsky fragment coupling reaction. The high convergence, efficiency, and modular nature of this synthesis make it amenable to the synthesis of structurally related compounds.",10.1021/ja0670660,2006-11-01,0.6406232822379064
Tetrahedron,Preparation of a benzenoid intermediate For use in the synthesis of Maytansine,,10.1016/s0040-4039(01)92752-2,1977-01-01,0.6406175893729061
Journal of the American Chemical Society,Short Total Synthesis of (±)-Sceptrin,"Gifted with novel chemical features and extraordinary biological activity, sceptrin has remained a prominent unanswered synthetic challenge since its characterization in 1981 by Faulkner and Clardy. A concise and practical solution to the myriad of chemical challenges posed by sceptrin is reported in this Communication. Thus, through a sequence involving rearrangement of an oxaquadricyclane, a new method for chemo- and regioselective halogenation, a mild sequence for 2-aminoimidazole formation, and careful synthetic choreography, (+/-)-sceptrin is obtained in a minimum of steps and in 24% overall yield from dimethyl acetylenedicarboxylate without a single use of chromatography.",10.1021/ja049648s,2004-03-01,0.6406113751262102
Journal of the American Chemical Society,Total Synthesis of Viridin and Viridiol,"The asymmetric total synthesis of (−)-viridin and (−)-viridiol, antifungal metabolites, was achieved in 17 and 18 steps from a commercially available starting material. An intramolecular [3+2] cycloaddition was applied to an easily available l -ribose derivative in order to construct the highly substituted D ring containing the key chiral cis -triol fragment. Co-catalyzed metal-hydride H atom transfer (MHAT) radical cyclization was utilized to form the C-ring and the all-carbon quaternary center at C-10. This convergent strategy provides a scalable approach to prepare viridin and viridiol for biological studies.",10.1021/jacs.9b08577,2019-09-26,0.6406085143231046
Tetrahedron,"An efficient synthesis of a new class of spiroheterocycles: diastereoselective synthesis of dihydropyrrolo[2,1-a]isoquinolines",,10.1016/j.tetlet.2007.07.135,2007-07-31,0.640607398297884
Organic Letters,Synthesis of a Neamine Dimer Targeting the Dimerization Initiation Site of HIV-1 RNA,"A neamine dimer designed to bind to a specific sequence of HIV-1 RNA has been synthesized. Starting from neomycin B (1), a five-step synthesis efficiently provided a key protected neamine monomer 6 (28%). From the latter, coupling reactions with activated diacids gave dimers. After deprotection, a neamine dimer was obtained as the hexachlorohydrate salt 15 with 13% overall yield over nine steps.",10.1021/ol701760k,2007-10-01,0.6406068103164572
Journal of the American Chemical Society,Total Synthesis of Papulacandin D,"A total synthesis of the antifungal agent papulacandin D is reported. The molecule is representative of a large class of C -aryl glycosides that exhibit significant antifungal activity. The synthetic strategy bifurcates the molecule into two nearly equal subunits, the arylglycoside and 18-carbon fatty acid side chain. The key strategic transformations are (1) the palladium catalyzed, organosilanolate-based cross-coupling of a protected glucal silanol and (2) a catalytic enantioselective allylation of a dienal using allyltrichlorosilane. The synthesis was accomplished in 31 steps overall from commercial starting materials to afford over 50 mg of the natural product.",10.1021/ja070071z,2007-02-17,0.6405960966935365
Angewandte Chemie International Edition,Efficient Enantioselective Total Synthesis of (−)‐Epipodophyllotoxin,"In only twelve steps the total synthesis of (−)-epipodophyllotoxin (2) has been completed starting from commercially available piperonal (1). The first stereocenter was formed under auxilary control, while the following epoxidation and radical cyclization proceeded with outstanding diastereoselectivity, which enabled the target molecule to be isolated in an overall yield of 30 % and with 97 % ee.",10.1002/anie.200351086,2003-06-05,0.6405930378058641
Tetrahedron,Ring expansion route to cycloheptane derivatives,,10.1016/s0040-4039(01)91872-6,1974-01-01,0.6405771988748175
Tetrahedron,"Asymmetric synthesis with chiral hydrogenolysable amines. Cyclic β-enamino ester reduction a diastereoselective route to 2,3-disubstituted pyrrolidines",,10.1016/s0040-4039(00)74247-x,1992-07-01,0.640574455794064
Synlett,Synthetic Studies Toward Tetrodecamycin: An Efficient Approach to the Core Structure of the Antibiotic,"An efficient synthetic pathway to the core structure 5 of the polyketide antibiotic tetrodecamycin (1a) has been developed. Our approach features the acid-catalyzed cyclization of a tert-butyldimethylsilyl protected methyl α-(γ-hydroxyacyl) tetronate, leading to the novel tricyclic ring skeleton exhibited by 5. An insight into the mechanism of this key ring closure step has been gained. Furthermore an alternative pathway to this ring skeleton, based on a fluoride ion induced desilylation-cyclization sequence, has been disclosed.",10.1055/s-2002-32952,2002-01-01,0.6405622301285613
Organic Letters,A Synthesis of a Spirocyclic Macrocyclic Protease Inhibitor for the Treatment of Hepatitis C,The development of a convergent and highly stereoselective synthesis of an HCV NS3/4a protease inhibitor possessing a unique spirocyclic and macrocyclic architecture is described. A late-stage spirocyclization strategy both enabled rapid structure-activity relationship studies in the drug discovery phase and simultaneously served as the basis for the large scale drug candidate preparation for clinical use. Also reported is the discovery of a novel InCl3-catalyzed carbonyl reduction with household aluminum foil or zinc powder as the terminal reductant.,10.1021/acs.orglett.6b00331,2016-03-07,0.6405556026124313
Organic Process Research & Development,An Efficient Scalable Process for the Synthesis of <i>N-</i> Boc-2- <i>tert</i> -butyldimethylsiloxypyrrole,"A safe, reliable and scalable process for the preparation of N- Boc-2- tert -butyldimethylsiloxy-pyrrole (TBSOP) is described. In a three-step, one-pot sequence (±)-4-amino-3-hydroxybutyric acid was converted to N- Boc-4-hydroxy-2-pyrrolidinone. This stable crystalline product was isolated by filtration directly from the reaction mixture. Dehydration followed by enolization and silylation produced the target compound without the need for chromatographic purification. The process was demonstrated in the pilot plant to make multikilogram quantities of material in 85% overall yield.",10.1021/op025532+,2002-05-17,0.6405465233865314
Organic Letters,First Total Synthesis of Pandamarine,"The first total synthesis of pandamarine, an alkaloid isolated from Pandanus amaryllifolius is reported. The key step of this extremely short (six steps in total) and protecting group-free synthesis is a highly efficient cascade reaction sequence initiated by the photooxidation of an easily accessible and symmetric difuran precursor.",10.1021/acs.orglett.5b01693,2015-06-30,0.6405245095973505
Organic Letters,Total Synthesis of (−)-Aurantioclavine,The concise total synthesis of (-)-aurantioclavine has been achieved by taking advantage of strategies for the asymmetric alkenylation of N-tert-butanesulfinyl imines. The enantiomerically pure natural product was prepared in 6 steps and 27% overall yield by using Rh-catalyzed addition of a N-methyliminodiacetic acid (MIDA) boronate and in 5 steps and 29% yield by employing a Grignard reagent addition sequence.,10.1021/ol100470g,2010-03-31,0.6405169646852458
Organic Letters,Enantioselective Total Synthesis of (+)-Leucascandrolide A Macrolactone,"[reaction: see text] The enantioselective synthesis of the (+)-leucascandrolide A macrolactone has been achieved in 20 linear steps from 1,3-propanediol. The key steps in the synthesis are a reductive cleavage of bicyclic ketal 5 to establish the C15 stereogenic center and a diastereoselective aldol of the boron enolate of methyl ketone 3 to aldehyde 4 in preparation for a heteroconjugate addition for the introduction of the C3 stereocenter.",10.1021/ol035797o,2003-10-29,0.6405144132786433
Synlett,Alternative Synthesis of the PDE5 Inhibitor RWJ387273 (R290629),An alternative synthesis of a PDE5 inhibitor is reported using a highly diastereoselective Pictet-Spengler reaction.,10.1055/s-2007-970769,2007-03-01,0.6405021481143363
European Journal of Organic Chemistry,Diversity‐Oriented Approach to Normuscopyridine and Its Analogues through Ring‐Closing Metathesis,"Abstract Ring‐closing metathesis (RCM) is a useful protocol for assembling macrocycles. To synthesize normuscopyridine, and its analogues we used RCM as a key step in our strategy. Our approach to the synthesis of pyridine macrocycles involves two routes. The first approach starts with alkenylation of 2,6‐bis[(phenylsulfonyl)methyl]pyridine and involves five steps with 10 % overall yield. The second route begins with Grignard addition to pyridine‐2,6‐dicarbo nitrile, followed by RCM and one‐pot removal of the carbonyl group before hydrogenation of the double bond in 28 % overall yield. This approach has only three steps. Neither route involves the use of protecting groups. Various points of diversification are embedded in our strategy and eight different cyclophanes were assembled by adopting a general approach to these macrocyclics.",10.1002/ejoc.201301493,2013-12-05,0.6404984842737795
Synlett,An Enantioselective Deprotonation Route to a Versatile Intermediate for C-Nucleoside Synthesis,,10.1055/s-1991-20716,1991-01-01,0.6404913648766056
Angewandte Chemie International Edition,Formal Synthesis of Leucascandrolide A,"Asymmetric allylation reactions of stannane-derived allyl diazaborolanes, and the use of the Terashima reagent for the highly selective asymmetric hydride reduction of a β-alkoxy ketone are key features of a highly convergent, stereocontrolled formal synthesis of leucascandrolide A (see picture).",10.1002/anie.200351817,2003-08-22,0.6404856691649182
Journal of Organic Chemistry,Stereoselective Total Synthesis of (±)-Pleurospiroketals A and B,"A full account of our efforts toward the stereoselective total synthesis of sesquiterpenoid-derived natural products (±)-pleurospiroketals A and B is described. Commercially available 3-methyl-2-cyclohexenone and 2,2-dimethyloxirane were used as key building blocks, and the substrate-controlled stereoselection was exploited to access the entire stereochemistry of these natural products. Initially, a planned synthetic route involving a [6,5]-bicyclic lactone intermediate was found to be insurmountable, and the later strategy comprising OsO 4 -NMO-mediated dihydroxylation of 3-methyl-2-cyclohexenone, followed by Luche reduction, Eschenmoser methylenation, and Brønsted acid-induced spiroketalization steps, was ultimately identified as the reliable strategy.",10.1021/acs.joc.1c01634,2021-09-21,0.6404666788305702
Journal of Organic Chemistry,Toward a Total Synthesis of the Immunosuppressant Sanglifehrin A. Preparation of Two Relay Compounds by Degradation and Their Use in the Reassembly of the Natural Product,"A potential relay route for the synthesis of the novel immunosuppressive agent sanglifehrin A ( 1 ) has been developed. Degradation of 1 by a sequence involving regioselective dihydroxylation of the C26,C27 double bond, followed by periodate cleavage of the resulting diol 4, afforded lactol 2 and macrocyclic aldehyde 3 . Intramolecular ketal formation between the 1,3-diol and ketone functions present in 3 gave ketal−aldehyde 5 . Lactol 2 was converted into sulfone 14 in four steps. The fragments 5 and 14 were reassembled, using the Julia−Kocienski olefination procedure, to afford intermediate 15, which was converted back to sanglifehrin A ( 1 ) after two deprotection steps.",10.1021/jo9912395,1999-12-01,0.6404525519352606
Journal of Organic Chemistry,Total Synthesis of Norbadione A,"A short, convergent synthesis of the mushroom pigment norbadione A is described. The construction of an appropriately substituted naphtholactone intermediate involved a regioselective Diels-Alder reaction between a bis(triisopropylsilyloxy)diene and 2,6-dichlorobenzo-1,4-quinone. A double Suzuki-Miyaura cross-coupling between a diboronate and two identical enol triflates was another key feature of the synthesis.",10.1021/jo702106u,2007-12-01,0.6404034049452013
Journal of Organic Chemistry,A<i>trans</i>-AB-Bacteriochlorin Building Block,"Synthetic bacteriochlorins are of interest for fundamental studies in photochemistry because of their strong absorption in the near-infrared spectral region and close similarity with natural bacteriochlorophylls. A de novo route to 5-methoxybacteriochlorins entails self-condensation of a dihydrodipyrrin-acetal, which in turn is prepared from a 2-(2-nitroethyl)pyrrole species and an α,β-unsaturated ketone-acetal (e.g., 1,1-dimethoxy-4-methylpent-3-en-2-one). Here, four new results are reported concerning the synthesis of substituted bacteriochlorins. First, a new, scalable route to 1,1-dimethoxy-4-methylpent-3-en-2-one removes a significant previous impediment to the overall route. Second, the new route was employed to gain access to new α,β-unsaturated ketones and corresponding dihydrodipyrrins bearing alternative substituents in place of the dimethoxy unit. Third, a dihydrodipyrrin bearing a 1,3-dioxolan-2-yl moiety afforded the bacteriochlorin (30% yield) containing a 2-hydroxyethoxy substituent at the 5-position. Fourth, subsequent bromination proceeded regioselectively at the 15-position to give a trans-(5,15)-AB-bacteriochlorin building block. The linear 5,15-substitution pattern is attractive for a number of molecular designs. The results taken together afford deeper understanding of the scope and limitations of the de novo route and also advance the capabilities for tailoring synthetic bacteriochlorins.",10.1021/jo201967k,2011-10-28,0.6403913643226854
Organic Letters,"Studies Directed toward the Synthesis of Terreulactone A:  Rapid Construction of the A, B, C Rings","[structure: see text]. An efficient, rapid synthesis of the A, B, C rings of terreulactone A is described. Key steps in the synthesis include a diastereoselective benzylic acid rearrangement to create the desired quaternary center at C2 and a mild bromolactonization to assemble the lactonic ring A.",10.1021/ol052618p,2006-01-12,0.6403844324202954
Organic Letters,Total Synthesis of (−)-Nemorosone and (+)-Secohyperforin,"A general strategy for the synthesis of polycyclic polyprenylated acylphloroglucinols is described in which a scalable, Lewis acid catalyzed epoxide-opening cascade cyclization is used to furnish common intermediate 4. The utility of this approach is exemplified by the total syntheses of both ent-nemorosone and (+)-secohyperforin, which were each accomplished in four steps from this intermediate.",10.1021/acs.orglett.5b01121,2015-06-30,0.6403687102617915
Journal of Organic Chemistry,A Highly Convergent Synthesis Route for Adda: A Non-Proteinogenic Amino Acid Unit in Cyanobacteria,"We report a concise nine-step synthesis of Boc-Adda-OH, a key residue in bioactive cyanobacterial peptides. The route features a regio- and stereoselective intermolecular Heck reaction to form a stable isoxazolidin-5-one, followed by N-O bond cleavage. This efficient, convergent approach offers excellent stereocontrol and functional group tolerance, facilitating access to Adda for natural product synthesis, environmental monitoring, and toxicological studies.",10.1021/acs.joc.5c01357,2025-08-01,0.6403578740623481
Organic Process Research & Development,Development of an Improved Route to a Human Immunodeficiency Virus Maturation Inhibitor by Chromium-Free Allylic Oxidation and an Efficient Asymmetric Henry Reaction,"Development of an improved route to a human immunodeficiency virus maturation inhibitor is described. Key features of the chemistry that was developed include avoidance of chromium reagents by use of a novel allylic oxidation with NBS/water and an aldehyde oxidation using either bleach/TEMPO under flow conditions or dichlorodimethylhydantoin in batch. It was demonstrated that an imine could be used for in situ protection of a labile aldehyde, and the mixed anhydride for the acetylation was optimized. A highly enantioselective Henry reaction was developed, and it was demonstrated that hazardous Raney nickel could be replaced by hydrogenation over platinum.",10.1021/acs.oprd.1c00374,2022-02-01,0.6403494779601061
Synthesis,Formal Convergent Synthesis of Ivermectin Aglycone - A Synthetic Approach to the C10-C25 Subunit of Avermectins 2b,International audience,10.1055/s-0029-1216954,2009-08-21,0.6403246726134856
Synthesis,"Regioselective and Facile Synthesis of 7,9-Dialkyl-8-oxopurines from 7,9-Dialkyl-7,8-dihydropurines: Total Synthesis of Heteromines I and J","A novel protocol for the synthesis of 6-halo-8-oxo-7,8-dihydro-9 H -purines based on the oxidation of 7,9-dialkyl-7,8-dihydro-9 H -purines has been developed. The presented methodology was used as a key step in the synthesis of heteromines I and J.",10.1055/s-0033-1340499,2014-01-09,0.6403193037840338
Organic Process Research & Development,Development of a Telescoped Alkylation/Reduction Reaction Sequence and an Asymmetric Hydrogenation to Enable the Kilogram Synthesis of ABBV-3748,"Challenges in the synthesis of the cystic fibrosis transmembrane receptor corrector ABBV-3748 were addressed to enable a multikilogram-scale GMP sequence. Implementation of an early-stage telescoped titanium-mediated alkylation and palladium-catalyzed hydrogenation limited the formation of a dimerization impurity and provided consistent yields across reaction scales. Development of late-stage enantioselective hydrogenation installed the stereocenter present in the active pharmaceutical ingredient. Aspects of reagent and catalyst selection, reaction optimization, and crystallization in these two key synthetic steps are described herein.",10.1021/acs.oprd.2c00245,2022-09-29,0.6403082332862676
Journal of Organic Chemistry,"Phellilane L, Sesquiterpene Metabolite of <i>Phellinus linteus</i>: Isolation, Structure Elucidation, and Asymmetric Total Synthesis","A new cyclopropane-containing sesquiterpenoid, phellilane L (1), was isolated from the medicinal mushroom Phellinus linteus (""Meshimakobu"" in Japanese), a member of the Hymenochaetaceae family and a well-known fungus that is widely used in East Asia. The planar structure of 1 was determined on the basis of spectroscopic analysis. The authors achieved the first total synthesis of 1. Our protecting group-free synthesis features a highly stereoselective one-pot synthesis involving an intermolecular alkylation/cyclization/lactonization strategy for construction of the key cyclopropane-γ-lactone intermediate. Additionally, our synthesis determined the absolute configuration of phellilane L (1).",10.1021/acs.joc.7b02141,2017-11-01,0.6403080562446875
Synthesis,"A Modular Synthesis of Fluorinated, Chiral Polar Lipids","The synthesis of a small collection of chiral, polar lipids is described starting from (S)-solketal and epichlorohydrin.",10.1055/s-0030-1258413,2011-01-19,0.6403058780454056
Tetrahedron,"A novel synthetic route to 2-alkylpropane-1,3-sultones and its application to the synthesis of 2-alkyl derivatives of tramiprosate",,10.1016/j.tetlet.2007.10.042,2007-10-30,0.6403020641374907
Journal of Organic Chemistry,"Synthesis of NK109, an Anticancer Benzo[<i>c</i>]phenanthridine Alkaloid","A total synthesis of NK109 (7-hydroxy-8-methoxy-5-methyl-2,3-methylenedioxybenzo[ c ]phenanthridinium hydrogensulfate dihydrate), an anticancer benzo[ c ]phenanthridine alkaloid, is reported. The primary structure of this compound was erroneously communicated in 1973 as fagaridine (from Fagara xanthoxyloides ) which is the 8-hydroxy regioisomer. NK109 has not yet been isolated from a natural source and therefore can only be obtained by synthesis. To study a wide variety of analogues, we decided to use a synthetic route via substituted benzylamine 5, which was obtained from the appropriate benzaldehyde and naphthylamine units. The benzo[ c ]phenanthridine ring was constructed by radical cyclization with tri- n -octyltin hydride and 2,2‘-azobis(2-methylbutyronitrile), followed by oxidative aromatization with MnO 2 . The resulting benzo[ c ]phenanthridine 6 was successfully methylated with methyl 2-nitrobenzenesulfonate. After deprotection of the benzyl group and subsequent hydration, NK109 was obtained. All reactions were performed under normal conditions. Purification was achieved only by recrystallization to give an overall yield of 40%.",10.1021/jo9718758,1998-06-01,0.6402999798307608
Synlett,Synthesis of 5-N-Substituted Tetrazole Derivatives of the Potent NK1 Receptor Antagonist GR203040,(opens in new window) Buy Article (opens in new window) Permissions and Reprints (opens in new window) All articles of this category (opens in new window) A series of amino-tetrazole derivatives of GR203040 were synthesised as potential NK 1 receptor antagonists. The synthesis of these analogues utilised a novel reaction sequence in which 1-aryl tetrazoles were converted to 1-aryl-5-amino-tetrazoles via a cyanoamide intermediate. neurokinin-1-receptor antagonist - aminotetrazole - cyanoamide,10.1055/s-1996-5420,1996-04-01,0.640293725482581
Journal of Organic Chemistry,Epoxyalcohol Route to Hydroxyethylene Dipeptide Isosteres. Stereodivergent Synthesis of the Diamino Alcohol Core of Ritonavir and Its C-2 Epimer,"A stereoselective synthesis of hydroxyethylene dipeptide isosteres based on the 1,4-diamino-2-hydroxybutane structure is described. Horner-Emmons olefination of phosphonates derived from alpha-amino acids, stereoselective reduction of the resulting enones to allylic alcohols, and syn epoxidation of the latter lead to enantiomerically pure 1-amino-2-hydroxy-3,4-epoxybutanes, key intermediates in the synthesis. Reductive cleavage of the epoxy alcohols with Red-Al proceeds in a highly regioselective way, giving 1-amino-2,4-dihydroxybutanes, from which diamino alcohol hydroxyethylene isosteres are obtained by selective protection of the secondary 2-hydroxy group, via cyclization to 1,3-oxazolidinone, and further elaboration of the 4-hydroxy. Both C-2 epimers of 1,4-diamino-2-hydroxybutanes are accessible by appropriate choice of the conditions for cyclization. The approach is demonstrated by the synthesis of a series of six hydroxyethylene dipeptide isosteres, including the diamino alcohol core of potent HIV-protease inhibitor ritonavir 18 and its C-2 epimer 11a.",10.1021/jo025616g,2002-11-01,0.6402865857389973
European Journal of Organic Chemistry,First Enantioselective Synthesis of Surinamensinol B and a Non‐Natural Polysphorin Analogue by a Two‐Stereocentered Hydrolytic Kinetic Resolution,"Abstract An efficient and economical approach to the synthesis of antitumor and anti‐inflammatory surinamensinol B ( 1 ) and antimalarial polysphorin analogue 2 has been achieved with high enantiomeric purity (96 % ee ) by starting from commercially available 3,4,5‐trimethoxybenzaldehyde. The key steps of the strategy include a Co‐catalyzed two‐stereocentered hydrolytic kinetic resolution (HKR) of racemic 2‐[(methoxymethoxy)(3,4,5‐trimethoxyphenyl)methyl]oxirane ( 13 ) as the chiral inducing step followed by a Mitsunobu reaction. Chiral epoxide 14 and chiral diol 15 were utilized in the syntheses of both compounds.",10.1002/ejoc.201501009,2015-10-13,0.6402627663865978
Synlett,An Efficient Stereocontrolled Synthesis of (-)-Stypoldione,"All articles of this category An efficient synthesis of (-)-stypoldione ( 3 ), via (-)-stypoldiol ( 1 ), was accomplished starting from S -(+)-carvone ( 4 ) using an IMDA reaction, a sonochemical Barbier reaction and an acid-catalysed quinol-tertiary alcohol cyclization as key synthetic steps. Stypoldiol - stypoldione - carvone - spirobenzodihydrofuran - IMDA",10.1055/s-1996-5601,1996-09-01,0.6402611569512534
Organic Letters,Bioinspired Total Synthesis of (±)-Yezo’otogirin C,"The first and protective group-free total synthesis of (±)-yezo'otogirin C has been achieved from 3-methyl-4-prenylcyclohex-2-enone in eight steps with 23% overall yield. The tricyclic core of (±)-yezo'otogirin C was established via a bioinspired oxidative cascade cyclization strategy using Mn(II)/Mn(III) and O2, followed by reduction of the peroxy-bridged intermediate using thiourea in refluxing methanol.",10.1021/ol403374h,2013-12-30,0.6402490911228638
Synthesis,Synthesis of an 1′-Azasugar Analogue of Maltose,All articles of this category Methyl 1′-azamaltoside ( 3 ) was synthesised from levoglucosane and d-galactose in a 16 step synthesis. Methyl 1′-azamaltoside ( 3 ) was found to inhibit glucoamylase with K i of 0.63 μM. glycosidase inhibitor - glucoamylase - reductive amination - isofagomine - glycosides - disaccharides - carbohydrates - nitrogen,10.1055/s-2001-10799,2001-01-01,0.6402475455964363
Synlett,"Preparation of a 3-Hydroxymethyl-2,4-pentadienyltin Reagent and Its Use in Alkaloid Synthesis; An Efficient Route to (±)-Nitraraine",,10.1055/s-1991-20851,1991-01-01,0.6402440566582209
Organic Letters,Enantioselective Total Synthesis of Otteliones A and B,Enantioselective total synthesis of otteliones A and B was accomplished. The key steps are radical cyclization of an alpha-iodoketone to construct the cis-hydrindanone skeleton and Suzuki-Miyaura coupling to incorporate the aromatic group. (+)-Ottelione A was converted to (-)-ottelione B on treatment with NaOH in THF.,10.1021/ol902776d,2010-03-11,0.6402328058276017
Journal of Organic Chemistry,"Enantioselective Total Synthesis of (+)-Lysergic Acid, (+)-Lysergol, and (+)-Isolysergol by Palladium-Catalyzed Domino Cyclization of Allenes Bearing Amino and Bromoindolyl Groups","Enantioselective total synthesis of the biologically important indole alkaloids (+)-lysergol, (+)-isolysergol, and (+)-lysergic acid is described. Key features of these total synthesis include (1) a facile synthesis of a chiral 1,3-amino alcohol via the Pd(0)- and In(I)-mediated reductive coupling reaction between L-serine-derived 2-ethynylaziridine and formaldehyde; (2) the Cr(II)/Ni(0)-mediated Nozaki-Hiyama-Kishi (NHK) reaction of an indole-3-acetaldehyde with iodoalkyne; and (3) Pd(0)-catalyzed domino cyclization of an allene bearing amino and bromoindolyl groups. This domino cyclization enabled direct construction of the C/D ring system of the ergot alkaloids skeleton, as well as the creation of the C5 stereogenic center with transfer of the allenic axial chirality to the central chirality.",10.1021/jo102388e,2011-03-01,0.640227607781187
Organic Letters,Stereoselective Synthesis of Microcarpalide,"The first total synthesis of the naturally occurring nonenolide, microcarpalide, is described. The key step in the synthesis was the ring-closing metathesis of a dienic ester prepared in turn by coupling an acid and an alcohol stereoselectively synthesized from (S,S)-tartaric acid and (R)-glycidol, respectively. [structure: see text]",10.1021/ol0265463,2002-08-30,0.6402223977067795
Journal of the American Chemical Society,"Unified Divergent Total Synthesis of Discorhabdin B, H, K, and Aleutianamine via the Late-Stage Oxidative <i>N,S</i>-Acetal Formation","This study achieved the total syntheses of (+)-discorhabdin B, (−)-discorhabdin H, (+)-discorhabdin K, and (−)-aleutianamine. A phenethylamine fragment bearing a o -pivaloylthio group, corresponding to the D/E/G ring moiety, was prepared from benzothiophen-2-carboxylic acid methyl ester and condensed with a known pyrroloiminoquinone derivative. The adduct was subjected to [bis(trifluoroacetoxy)iodo]benzene (PIFA)-promoted oxidative spirocyclization to furnish the A/B/C/D/E spirocyclohexadienone fused with pyrroloiminoquinone. The total synthesis of (±)-discorhabdin B was completed via the key construction of the highly strained G ring with the N, S -acetal moiety featuring a newly developed CuBr 2 -mediated oxidative cascade cyclization. The stereocontrolled total synthesis of (+)-discorhabdin B was accomplished by a diastereoselective PIFA-promoted oxidative spirocyclization using a chiral thioester. (−)-Disocrhabdin H and (+)-discorhabdin K were synthesized by the site- and face-selective thia-Michael addition of l -ovothiol A to (+)- N -Ts-discorhabdin B with the concomitant formation of the F ring by forming the C2–N18 bond. The total synthesis of (−)-aleutianamine was achieved via a skeletal rearrangement initiated by the Luche reduction of the dienone moiety of (+)- N -Ts-discorhabdin B.",10.1021/jacs.3c06578,2023-08-09,0.6402177655484663
Journal of Organic Chemistry,A Convenient Synthesis of 2-(Alkylamino)pyridines,The synthesis of a series of 2-(alkylamino)pyridines (1) in three steps from 2-aminopyridine (4) is reported. The products were obtained in 67-91% overall yield from 4.,10.1021/jo020057z,2002-05-17,0.6402052833768987
Synthesis,PdI2/I2-Catalyzed Thiolation-Annulation of 2-Alkynylbenzyl Azides with Disulfides: Selective Synthesis of 4-Sulfenylisoquinolines,"A PdI2/I2-catalyzed thiolation-annulation route of alkynes with azides and disulfides for the synthesis of 4-sulfenylisoquinolines is described. This route allows numerous 2-alkynylbenzyl azides to react with disulfides or 1,2-diphenyldiselane leading to the corresponding 4-chalcogen-substituted isoquinolines in moderate to good yields.",10.1055/s-0030-1259965,2011-03-22,0.6402037275423261
Organic Process Research & Development,A Novel and Efficient Route to Zafirlukast,"Zafirlukast, an important drug for allergic pulmonary disorders such as asthma, is synthesized by a five-step, high-yielding, and inexpensive process.",10.1021/op049869i,2004-10-19,0.6402004650349604
Journal of the American Chemical Society,Total Synthesis of (+)-Fastigiatine,"The first total synthesis of the Lycopodium alkaloid (+)-fastigiatine has been accomplished in 15 steps and 30% overall yield from known compounds. Noteworthy transformations include a convergent fragment coupling via a nucleophilic cyclopropane opening, a highly diastereoselective formal [3 + 3]-cycloaddition, and a transannular Mannich reaction to construct the core of the natural product.",10.1021/ja104575h,2010-06-22,0.6401947491869086
Journal of Organic Chemistry,A Synthetic Route to Hexahydroimidazoquinolines via Ring-Opening Cyclization of Aziridines with Tetrahydroquinoline,"An efficient synthetic route to 1,2,3,3a,4,5-hexahydroimidazo[1,2- a ] quinolines in up to 70% yields with high stereoselectivity ( dr up to 89:11) via Lewis acid-catalyzed S N 2-type ring opening of activated aziridines with tetrahydroquinoline, followed by an intramolecular cyclization (ring-opening cyclization, ROC) in the presence of diethyl azo-dicarboxylate (DEAD) as an oxidant has been developed.",10.1021/acs.joc.5c02155,2025-11-07,0.6401819635488016
Journal of Organic Chemistry,"Synthesis of Guanine α-Carboxy Nucleoside Phosphonate (G-α-CNP), a Direct Inhibitor of Multiple Viral DNA Polymerases","The synthesis of guanine α-carboxy nucleoside phosphonate (G-α-CNP) is described. Two routes provide access to racemic G-α-CNP 9, one via base construction and the other utilizing Tsuji-Trost allylic substitution. The latter methodology was also applied to the enantiopure synthesis of both antipodes of G-α-CNP, each of which showing interesting antiviral DNA polymerase activity. Additionally, we report an improved multigram scale preparation of the cyclopentene building block 10, starting material for the preferred Tsuji-Trost route to 9.",10.1021/acs.joc.8b01124,2018-08-07,0.6401810083863324
Organic Process Research & Development,A Chiral Pool Strategy for the Synthesis of a SMARCA2 Degrading PROTAC,A scalable synthesis of the SMARCA2 degrading PROTAC 1 was developed. The linker fragment was derived from ( S )-citronellol by oxidative cleavage and diastereoselective aryl Grignard addition to a derived N - tert -butanesulfinyl aldimine for generation of the chiral amine stereocenter and a one-pot borylation/Suzuki reaction for biaryl formation. The dipeptide fragment was prepared by T3P-mediated coupling of hydroxyproline benzyl ester and N -Boc tert -leucine followed by capping with 1-fluorocyclopropancarboxylic acid and ester hydrolysis. Unification of the linker with the SMARCA2 binding motif and dipeptide was achieved by sequential reductive amination and coupling. The synthesis did not require any preparative or chiral HPLC purifications and was used to prepare over 100 g of 1 .,10.1021/acs.oprd.4c00048,2024-03-20,0.6401645956106158
Synthesis,Synthesis of New Ethyl 3-Amino-4-arylfuran-2-carboxylates,An efficient method for the preparation of new ethyl 3-amino-4-arylfuran-2-carboxylates is described. The synthesis proceeds via the corresponding hydroxyacrylonitrile sodium salt and an intermediate malonate vinyl ether. The last step of ring closure afforded the ethyl 3-amino-4-arylfuran-2-carboxylates in 15% to 40% yields.,10.1055/s-2002-25772,2002-01-01,0.6401631728246822
Organic Letters,"Synthesis of a Dicyano Abietane, a Key Intermediate for the Anti-inflammatory Agent TBE-31","The synthesis of dicyano abietane 11, a potential precursor to the biologically active tricyclic bis-cyano enone 6 (TBE-31), was accomplished in eight steps from epoxide 13. The synthesis features a Lewis acid promoted stereoselective cyclization of epoxide 13 to generate the tricyclic ring system 12 in one step.",10.1021/ol403289y,2013-12-04,0.6401601152726965
Journal of Organic Chemistry,"Synthesis of 1,3,6-Trisubstituted Azulenes","We have developed a short, general synthetic route to 1,3,6-trisubstituted azulenes. The key intermediate, 6-methylazulene, was synthesized from readily available and inexpensive starting materials in 63% yield over two steps. The methyl group of 6-methylazulene was then used as a synthetic handle to introduce different substituents at the 6-position via two different methods. Subsequently, the 1- and 3-positions were substituted with additional functional handles, such as formyl, chloromethylketone, and iodide. The efficiency of the synthetic route was demonstrated by preparing a collection of three different products with the best demonstrated yield 33% over seven steps.",10.1021/acs.joc.5b02271,2015-11-03,0.6401409732654193
Journal of Organic Chemistry,"Total Synthesis of nor-1,6-Germacradien-5-ols","The first total synthesis of (+/-)-nor-1,6-germacradien-5-ols is described. The synthetic route involves the RCM methodology for the ring formation and a selective 1,2 addition of MeLi to cyclodecenone. By altering the order of the last synthetic steps, TBSO-protected (+/-)-(1Z,6E)-nor-1,6-germacradien-5-ols (+/-)-(5S*,8R*)-16 and -(+/-)-(5S*,8S*)-16 were obtained. The synthetic strategy via cyclodecenone offers the possibility of preparing different analogues of the title compounds through addition of other nucleophiles. Moreover, nor-germacrene D could be accessed from the target molecule by methylenation of its carbonyl moiety. (+/-)-nor-1,6-Germacradien-5-ol [(+/-)-(1E,5S*,6E,8S*)-2] was synthesized in eight steps from isovaleric acid. The 10-membered ring was formed by RCM, and the tertiary alcohol moiety was introduced in the last step via a highly diastereoselective addition of MeLi to (+/-)-(1E,6E)-1,6-cyclodecen-5-one (+/-)-E,E-5. Addition of MeLi to cyclodecenone (+/-)-Z,E-5 also occurred with complete selectivity to provide (+/-)-(1Z,5S*,6E,8S*)-2. A slightly different synthetic pathway was also explored, in which the order of the final synthetic steps was switched: the enone formation and the addition of MeLi were conducted prior to the cyclization. When the hydroxy group was protected as a TBS ether, the newly formed olefin had exclusively Z configuration. Thus, TBSO-protected (+/-)-(1Z,6E)-nor-1,6-germacradien-5-ols (+/-)-16 were obtained as a 1:1 (5S*,8S*)/(5R*,8S*) mixture. The NMR spectra of these two diastereomers confirmed the relative stereochemistry of natural (-)-1,6-germacradien-5-ol (1) at C5 and C8.",10.1021/jo016110l,2002-02-08,0.6401385118461119
Tetrahedron,Rearrangements of O-protected glycosylenamines. A new and efficient route for the synthesis of O-protected 4-aminoaldoses,,10.1016/0040-4039(95)01737-3,1995-11-01,0.6401365675906009
Journal of Organic Chemistry,A Total Synthesis of Bifidenone,"The first total synthesis of bifidenone, a novel natural tubulin polymerization inhibitor, has been achieved in 12 steps starting from commercially available 1,4-dioxaspiro[4.5]decan-8-one. The synthesis includes a newly developed method to generate the dihydrobenzodioxolone core by palladium-catalyzed aerobic dehydrogenation. The three stereocenters were installed with an AD-mix-β dihydroxylation step followed by a late-stage palladium-catalyzed decarboxylation-allylation procedure. The absolute stereochemistry of 3 was determined via 13a by single-crystal X-ray analysis.",10.1021/acs.joc.7b00202,2017-03-29,0.6401270428077863
Journal of the American Chemical Society,Unified Strategy for the Synthesis of the “Miscellaneous” <i>Lycopodium</i> Alkaloids: Total Synthesis of (±)-Lyconadin A,"Total synthesis of the Lycopodium alkaloid lyconadin A was achieved in 18 steps starting from a readily available vinylogous ester and bromopicoline. The key step in the total synthesis is a proximity-driven oxidative C-N bond-forming reaction that yields the lyconadin pentacycle from a tetracyclic precursor. The key tetracycle, which has been prepared for the first time, is a versatile intermediate that may be utilized for the total synthesis of a variety of Lycopodium alkaloids. Critical to the success of this plan was the efficient preparation of a pyridine-annulated cycloheptadiene tricycle that promises to be a general strategy to access a variety of seven-membered ring containing natural products.",10.1021/ja8028069,2008-05-14,0.6401230777472975
Tetrahedron,"An efficient and novel approach to the synthesis of tetrahydrophenanthro[4,3-b]thiophenes",,10.1016/j.tetlet.2007.05.024,2007-05-11,0.6401179959777047
Synthesis,"Synthesis of Optically Active Indolizidines: (-)-8a-epi-Dendroprimine and (-)-7,8-Dehydro-5,6-dimethylindolizidine","All articles of this category Indolizidinones can be employed as key intermediates in efficient asymmetric synthesis of naturally occurring indolizidine alkaloid analogues. The 5,7-dimethylindolizidine (-)-8a- epi -dendroprimine was formed by a diastereoselective methylation-reduction sequence of the lactam function. The (-)-5,6-dimethylindolizidine was generated via the same key step including an additional quasi 1,2-methyl shift: an intramolecular enamine alkylation is followed by regioselective reductive cyclopropane ring opening. indolizidinone - indolizidine - intramolecular enamine alkylation - iminium salt - diastereoselective reduction - radical cyclopropane opening",10.1055/s-1999-3396,1999-02-01,0.6400861739890477
Tetrahedron,β-Pinene-6-one: a pivotal synthetic intermediate,,10.1016/s0040-4039(98)01399-9,1998-09-01,0.6400854347858986
Journal of the American Chemical Society,Enantioselective Total Synthesis of (+)-Alterbrassicicene C,"Herein, the first total synthesis of (+)-alterbrassicicene C ( 2 ) is described. Key features of the synthesis include an oxiranium mediated ether ring expansion, an oxa-Michael/retro-oxa-Michael cascade, and installation of a vinyl methoxy ether moiety via Stille coupling.",10.1021/jacs.2c12275,2022-12-23,0.6400541051057669
Journal of Organic Chemistry,Synthetic Studies on Amipurimycin: Total Synthesis of a Thymine Nucleoside Analogue,"Amipurimycin, a member of the complex peptidyl nucleoside family of antibiotics, is a Streptomyces-derived potent antifungal agent. The mechanism of action of amipurimycin, however, remains undetermined. Additionally, there are no reports on the total synthesis or structure-activity relationships (SAR) of this potentially useful bioactive compound. In a study aimed at the total synthesis and SAR studies of this natural product, the present research reports the development of a synthetic route to the central pyranosyl amino acid core of amipurimycin and its further elaboration, culminating in the synthesis of a unique thymine analogue. Utilizing a d-serine-derived dihydroaminopyrone as a strategic building block, the synthesis involves de novo construction of the fully functionalized C-3-branched carbohydrate amino acid core, followed by glycosidic attachment of thymine at C-1, and peptidic linking of the C-6 amine with the 1,2-aminocyclopentane carboxylic acid side chain.",10.1021/jo8004815,2008-05-09,0.6400495104838609
European Journal of Organic Chemistry,"Convergent Syntheses of <i>N</i>‐Boc‐Protected (2<i>S</i>,4<i>R</i>)‐4‐(<i>Z</i>)‐Propenylproline and 5‐Chloro‐1‐(methoxymethoxy)pyrrol‐2‐carboxylic Acid − Two Essential Building Blocks for the Signal Metabolite Hormaomycin","Abstract An efficient and scalable synthesis of enantiomerically pure N ‐Boc‐protected 4‐( Z )‐propenylproline ( 15 ) using the conventional Wittig reaction to construct the double bond has been developed [11% yield over 8 steps from N ‐Boc‐protected (2 S ,4 R )‐4‐hydroxyproline, 7 ]. The O ‐MOM‐protected 5‐chloro‐1‐hydroxypyrrole‐2‐carboxylic acid [Chpca(MOM)‐OH ( 29 )] was prepared along a reasonably efficient synthetic route applying the thermal rearrangement of 2‐azido‐6‐chloropyridine N ‐oxide ( 22 ) as a key step in fairly good overall yield [9% over 7 steps from easily accessible 2,6‐dichloropyridine N ‐oxide ( 21 )]. The suitability of the MOM‐protected N ‐hydroxy group during the preparation of the N ‐hydroxypyrroles functionalized at C‐2, was confirmed by the successful synthesis of Chpca‐(3‐Ncp)Ala‐OFM 33 obtained from the acylated amino ester Chpca(MOM)‐(3‐Ncp)Ala‐OFM 32 , which was selectively deprotected leaving the sensitive N ‐hydroxypyrrole unit intact. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2004)",10.1002/ejoc.200400480,2004-10-13,0.640026433094552
Tetrahedron,Tandem carbolithiation/cyclization of 2-(3-phenyl-2-propen-1-yl) oxazolines. A novel route to cyclobutane derivatives,,10.1016/s0040-4039(97)10298-2,1997-12-01,0.6400226661810768
Organic Letters,"Total Synthesis of the Formamicin Aglycon, Formamicinone","[structure: see text] The total synthesis of formamicinone (2), the aglycone of formamicin (1), has been accomplished via the late-stage Suzuki cross-coupling of fragments 5 and 6, the macrolactonization of seco ester 14, and the Mukaiyama aldol reaction of aldehyde 3 and methyl ketone 4. An efficient and highly stereoselective second generation synthesis of vinyl iodide 6 is also described.",10.1021/ol027569k,2003-01-14,0.6400133548842596
Journal of Organic Chemistry,"PdCl<sub>2</sub>/NaI-Catalyzed Homodimeric Coupling-Cyclization Reaction of 2,3-Allenols:  An Efficient Synthesis of 4-(1‘,3‘-Dien-2‘-yl)-2,5-dihydrofuran Derivatives","A PdCl2/NaI-catalyzed homodimeric coupling-cyclization reaction of 2,3-allenols was observed to provide an efficient route to 4-(1',3'-dien-2'-yl)-2,5-dihydrofuran derivatives. By using the easily available optically active starting materials, 2,5-dihydrofurans with high enantiopurity may be prepared. A Pd(II)-catalyzed mechanism was also discussed.",10.1021/jo702332m,2007-12-19,0.6400099026136185
Journal of Organic Chemistry,"Stereoselective Synthesis of Protected (2<i>R</i>,3<i>R</i>,4<i>S</i>)-4,7-Diamino-2,3-dihydroxyheptanoic Acid:  A Novel Amino Acid of Callipeltins A and D","An orthogonally protected derivative 1 of (2R,3R,4S)-4,7-diamino-2,3-dihydroxyheptanoic acid, the unusual amino acid residue of the biologically active marine peptides such as callipeltins A and D and neamphamide A, was efficiently prepared in 10 steps and 30% overall yield from a commercially available L-ornithine derivative 2. The key step includes the N-diphenylmethylene-controlled diastereoselective dihydroxylation of (Z)-ester 3 with >13:1 selectivity for the desired isomer.",10.1021/jo052676o,2006-03-16,0.6399920111622696
Organic Letters,Total Synthesis of (−)-Melanthioidine by Copper-Mediated Cyclodimerization,An efficient asymmetric total synthesis of the dimeric macrocyclic diaryl ether phenethyltetrahydroisoquinoline alkaloid (-)-melanthiodine is reported. Key steps of the synthesis include an efficient Noyori asymmetric transfer hydrogenation to access the enantioenriched phenethyltetrahydroisoquinoline monomeric subunit and a copper-mediated cyclodimerization to form the two diaryl ether linkages with concomitant macrocyclization.,10.1021/acs.orglett.6b01496,2016-07-19,0.6399865393827372
European Journal of Organic Chemistry,Evolution of Concise and Flexible Synthetic Strategies for Trichostatic Acid and the Potent Histone Deacetylase Inhibitor Trichostatin A,"Abstract ( R )‐(+)‐Trichostatic acid and ( R )‐(+)‐trichostatin A (TSA) are natural products that have attracted considerable attention in the field of epigenetic therapies. TSA in particular is a naturally occurring hydroxamic acid having potent activity as a histone deacetylase inhibitor (HDACi) and having significant potential for treatment of a myriad of genetically based diseases. Development of TSA and other trichostatic acid derivatives into useful small‐molecule therapies has been hindered by the low natural abundance and high cost associated with these compounds. We report herein our collective efforts towards the development of concise and scalable routes for the synthesis of trichostatic acid and TSA in both racemic and enantioenriched forms. Three independent synthetic pathways were developed with varying degrees of efficiency and convergency. In the first synthesis, the key step was a vinylogous Horner–Wadsworth–Emmons condensation. A Marshall propargylation reaction was used as the key step in the second synthesis, and Pd‐catalyzed α‐alkenylation of a ketone zinc enolate by using various functionalized alkenyl or dienyl halides was developed for the third synthesis. The second pathway proved to be readily amenable to an enantioselective modification, and both the second and third pathways were straightforwardly adapted for the facile preparation of new analogues of trichostatic acid and TSA.",10.1002/ejoc.201201233,2012-11-20,0.6399704762351254
Tetrahedron,Alternative synthetic route for the pharmacophore of anticancer agent: Triazolopyridazine derivative,,10.1016/j.tetlet.2024.155193,2024-07-11,0.6399607812349426
Journal of Organic Chemistry,A Second Generation Synthesis of Roseophilin and Chromophore Analogues,"A concise, flexible, and high-yielding synthesis of the macrocyclic compound 4 is outlined which served as a key intermediate in a previous total synthesis of the antitumor active alkaloid roseophilin 1 . The key steps of this approach consist of a Pd(0)-catalyzed reaction of vinyloxirane 6 with sulfone 7 and in a subsequent ring closing metathesis (RCM) reaction for the formation of the 13-membered ring catalyzed by the ruthenium carbene Cl 2 (PCy 3 ) 2 Ru CHCH CPh 2 introduced by Grubbs. Moreover, nitrile ylide cycloaddition reactions are used for the preparation of roseophilin side chain mimics. Finally, the synthesis of various chromophore analogues of 1 is reported, including deschloro-desmethoxyroseophilin 12 which is the most elaborate derivative of this complex target reported so far.",10.1021/jo982088t,1999-03-12,0.6399546875674196
Journal of Organic Chemistry,Asymmetric Synthesis of <i>cis</i>-7-Methoxycalamenene via the Intramolecular Buchner Reaction of an α-Diazoketone,"The asymmetric synthesis of cis-7-methoxycalamenene 1 has been accomplished using the intramolecular Buchner reaction of α-diazoketone 7 as the key step in the synthetic route. Upon reduction of the equilibrating azulenone structure 8, the resulting azulenol 9 rearranges to dihydronaphthalene 10 containing the 6,6-membered bicyclic ring system characteristic of 1, by means of an acid-catalyzed aromatization process. Transformation of 10 to 1 is accomplished through a three-step reaction sequence.",10.1021/jo202499j,2012-01-19,0.6399476261830535
Journal of Organic Chemistry,"Efficient Large-Scale Synthesis of BILN 2061, a Potent HCV Protease Inhibitor, by a Convergent Approach Based on Ring-Closing Metathesis","A multistep scalable synthesis of the clinically important hepatitis C virus (HCV) protease inhibitor BILN 2061 (1) is described. The synthesis is highly convergent and consists of two amide bond formations, one etherification, and one ring-closing metathesis (RCM) step, using readily available building blocks 2-5. The optimization of each step is described at length. The main focus of the paper is the study of the RCM step and the description of the main problems faced when scaling up to pilot scale this highly powerful but very challenging synthetic operation. Eventually, the RCM reaction was smoothly scaled up to produce >400 kg of cyclized product.",10.1021/jo060285j,2006-08-17,0.6399333577194312
Organic Letters,PIFA-Mediated Oxidative Cyclization of 1-Carbamoyl-1-oximylcycloalkanes: Synthesis of Spiro-Fused Pyrazolin-5-one<i>N</i>-Oxides,"A convenient and efficient synthesis of spiro-fused pyrazolin-5-one N-oxides starting from readily available 1-carbamoyl-1-oximylcycloalkanes is developed. This general protocol features a novel and facile way for access to the five-membered azaheterocycles by formation of a new N-N single bond. The key cyclization step utilizes the formation of an N-oxonitrenium intermediate, mediated by the hypervalent iodine reagent PIFA, and its subsequent intramolecular trapping by the amide moiety under rather mild experimental conditions.",10.1021/ol802952e,2009-01-27,0.6399327186902398
Organic Process Research & Development,Development of a Scalable Synthesis of a Serotonin Receptor Antagonist,"An efficient process was developed for the manufacture of MSA100, a serotonin receptor antagonist, via a five-step synthetic route furnishing a high quality of active pharmaceutical ingredient. Highlights of this synthesis include: (1) replacing carcinogenic methyl iodide with methyl p -toluenesulfonate as the methylating reagent; (2) a hydrogenation protocol with optimized temperature, pressure, and mass-transfer conditions that avoided one side product and reduced the other one effectively; (3) chemical resolution employing D -camphoric acid in a mixed-solvent system; (4) amidation under anhydrous conditions for controlling a Michael adduct impurity; and (5) plausible mechanisms for the formation of side products.",10.1021/op5003402,2014-12-06,0.639913677949555
Organic Letters,"Enantioselective Total Synthesis of (−)-Candelalide A, a Novel Blocker of the Voltage-Gated Potassium Channel Kv1.3 for an Immunosuppressive Agent","A convergent route to (-)-candelalide A involved the union of a trans-decalin portion (AB ring) and a gamma-pyrone moiety through the C16-C3' bond to assemble the whole carbon framework and subsequent formation of the dihydropyran ring (C ring) as the crucial steps. A strategic [2,3]-Wittig rearrangement was employed for establishing the stereogenic center at C9 and an exo-methylene function at C8 present in the decalin portion. [reaction: see text]",10.1021/ol051398c,2005-07-27,0.6399070441475327
Organic Letters,"Total Synthesis of (−)-Minquartynoic Acid:  An Anti-Cancer, Anti-HIV Natural Product","[structure: see text] The tetraacetylenic compound, (S)-minquartynoic acid (1), is synthesized in seven linear steps and 17% overall yield from commercially available azelaic acid monomethyl ester. The key step is a one-pot three-component Cadiot-Chodkiewicz reaction to construct the tetrayne unit without using either a diyne or a triyne intermediate.",10.1021/ol026145n,2002-06-22,0.6398930059522258
Organic Process Research & Development,Manufacture of High-Purity Meloxicam via Its Novel Potassium Salt Monohydrate,"An improved procedure for the manufacture of 4-hydroxy-2-methyl- N -(5-methyl-1,3-thiazol-2-yl)-2 H -1,2-benzothiazine-3-carboxamide 1,1-dioxide (meloxicam) is described. The key intermediate of this protocol is the new potassium salt monohydrate of meloxicam, which makes possible the efficient removal of impurities, resulting in an environmentally friendly manufacturing process of the high-purity (>99.90%) drug substance.",10.1021/op900031h,2009-03-23,0.6398877240667522
Angewandte Chemie International Edition,Facile Construction of <i>N</i>‐Hydroxybenzazocine: Enantioselective Total Synthesis of (+)‐FR900482,"Intramolecular hydroxylamination of ω-formyl nitrobenzene 1 followed by stereoselective hydroxymethylation led to the formation of N-hydroxybenzazocine 2, a key intermediate in the enantioselective total synthesis of the antitumor antibiotic FR900482 (3).",10.1002/anie.200290016,2002-12-12,0.6398867897885825
Journal of Organic Chemistry,Inhibitors of 25-Hydroxyvitamin D<sub>3</sub>-1α-Hydroxylase:  A-Ring Oxa Analogs of 25-Hydroxyvitamin D<sub>3</sub><sup>1</sup>,"The most potent inhibitor known of 25-hydroxyvitamin D 3 1α-hydroxylase (1-OHase), a cytochrome P-450 mixed function oxidase involved in the production of the steroid hormone 1α,25-dihydroxyvitamin D 3 ( 2 ), is 25-hydroxy-3-deoxy-2-oxavitamin D 3 ( 3b ). The latter, prepared previously in relatively low yield, is unusual because it coexists in nearly equal proportions with its [1,7]-sigmatropic shifted, previtamin D 3 tautomer 4b . A more efficient synthesis of this potent inhibitor was developed by applying Trost's enyne Pd(0) cyclization strategy. Besides succeeding in improving the synthesis of 3b / 4b, extension of this approach to the synthesis of other related A-ring oxacycles for structure−function studies of the 1-OHase system has been successful. This venture has resulted not only in oxacycles 4a, 3b / 4b, and 3c but also their 9,11-didehydro counterparts 5a, 5b, and 5c . The analog 5b was anticipated to be of particular interest because it represents an analog of the potent inhibitor 3b, but the presence of the 9,11-double bond renders it incapable of undergoing a [1,7]-sigmatropic shift to a form resembling 4b . Biological evaluation of 5b revealed it to be a more potent inhibitor of 1-OHase than 3b / 4b, suggesting that 3b is the likely form of the inhibitor 3b / 4b . Initial kinetic experiments indicate that the analogs ( 3b, 3c, and 5b ) tested do not inhibit by direct mechanism-based enzyme inactivation, revealing rather that inhibition of 1-OHase is competitive. Finally, it should be noted that the synthetic studies described herein provide new information regarding the scope and limitations of the palladium(0)-mediated enyne cyclization strategy leading to vitamin D molecules.",10.1021/jo960498g,1996-01-01,0.6398793918137871
Tetrahedron,Synthesis of a new antimicrobial aminoglycoside employing maltose as a key starting material,,10.1016/s0040-4039(00)96231-2,1987-01-01,0.6398491958117998
Journal of Organic Chemistry,"Enantioselective Total Synthesis of (+)-Monocerin, a Dihydroisocoumarin Derivative with Potent Antimalarial Properties","We describe here the enantioselective synthesis of (+)-monocerin and its acetate derivative. The present synthesis features an efficient optically active synthesis of the β-hydroxy-γ-lactone derivative with high enantiomeric purity using Sharpless dihydroxylation as the key step. The synthesis also highlights a tandem Lewis acid-catalyzed, oxocarbenium ion-mediated diastereoselective syn -allylation reaction, and a methoxymethyl group promoted methylenation reaction. We investigated this reaction with a variety of Lewis acids. A selective CrO 3 -mediated oxidation of isochroman provided the corresponding lactone derivative. The synthesis is quite efficient and may be useful for the preparation of derivatives.",10.1021/acs.joc.9b00414,2019-04-29,0.6398483503658893
Tetrahedron,Highly enantioselective organocatalytic synthesis of piperidines. Formal synthesis of (−)-Paroxetine,,10.1016/j.tetlet.2009.02.049,2009-02-13,0.6398482764424361
Journal of Organic Chemistry,Enantioselective Construction of a Polyhydroxylated Pyrrolidine Skeleton from 3-Vinylaziridine-2-carboxylates: Synthesis of (+)-DMDP and a Potential Common Intermediate for (+)-Hyacinthacine A<sub>1</sub> and (+)-1-<i>epi</i>-Australine,"We report an enantioselective synthesis of the polyhydroxylated pyrrolidine alkaloid (+)-DMDP. The key steps in the synthesis were guanidinium ylide mediated asymmetric aziridination, stereospecific ring opening of trans-3-vinylaziridine-2-carboxylate with an oxygen nucleophile, iodine-mediated 5-endo-trig amino cyclization, and Prévost displacement. In addition, a potential common intermediate for the polyhydroxylated pyrrolizidine alkaloids (+)-hyacinthacine A(1) and (+)-1-epi-australine was synthesized from a diastereoisomeric cis-aziridine coformed in the asymmetric aziridination using the same strategy. A rationale for the diastereoselectivity observed for the iodine-mediated amino cyclization reactions is proposed on the basis of the heats of formation of the products.",10.1021/jo301178b,2012-08-17,0.6398313906245859
Journal of the American Chemical Society,Enantioselective Synthesis of <i>des</i>-Epoxy-Amphidinolide N,"The synthesis of des -epoxy-amphidinolide N was achieved in 22 longest linear and 33 total steps. Three generations of synthetic endeavors are reported herein. During the first generation, our key stitching strategy that highlighted an intramolecular Ru-catalyzed alkene-alkyne (Ru AA) coupling and a late-stage epoxidation proved successful, but the installation of the α,α′-dihydroxyl ketone motif employing a dihydroxylation method was problematic. Our second generation of synthetic efforts addressed the scalability problem of the southern fragment synthesis and significantly improved the efficiency of the atom-economical Ru AA coupling, but suffered from several protecting group-based issues that proved insurmountable. Finally, relying on a judicious protecting group strategy together with concise fragment preparation, des -epoxy-amphidinolide N was achieved in a convergent fashion. Calculations disclose a hydrogen-bonding bridge within amphidinolide N. Comparisons of 13 C NMR chemical shift differences using our synthetic des -epoxy-amphidinolide N suggest that amphidinolide N and carbenolide I are probably identical.",10.1021/jacs.8b11827,2018-11-20,0.6397987277164948
Tetrahedron,"The reaction of diazomethane with chloroazirines: A new route to 1,2,3-triazines",,10.1016/s0040-4039(01)81784-6,1981-01-01,0.6397960924216364
Tetrahedron,"The reaction of dialkylmalonyl dichlorides with 1,3-diaminopropanes a new route to macrocyclic polyamides and polyamines",,10.1016/s0040-4039(01)92690-5,1977-01-01,0.6397960924216364
Synlett,Total Synthesis of (+)-Camptothecin via an Intramolecular Palladium-Catalyzed Cyclization Strategy,The novel cascade intramolecular Pd-catalyzed cyclization followed by aromatization for the construction of d ring of (+)-camptothecin as a key step is demonstrated.,10.1055/s-2007-991054,2007-09-25,0.639782747954833
Angewandte Chemie International Edition,Re<sub>2</sub>O<sub>7</sub>‐Mediated Dehydrative Cyclization Reactions: Total Synthesis of Herboxidiene and Its 12‐Desmethyl Analogue,"catalysis effects efficient and stereoselective dehydrative cyclization reactions from monoallylic diols, with stereocontrol arising from thermodynamic equilibration. This method was applied to a rapid synthesis of the spliceosome inhibitor herboxidiene. The route was also utilized for the synthesis of an analogue that highlights the importance of a single methyl group in biasing the conformation in the acyclic region of the molecule.",10.1002/anie.201705924,2017-07-07,0.6397678626369084
Journal of Organic Chemistry,"Stereoselective Photochemical 1,3-Dioxolane Addition to <i>5-</i>Alkoxymethyl-2(5<i>H</i>)-furanone:  Synthesis of Bis-tetrahydrofuranyl Ligand for HIV Protease Inhibitor UIC-94017 (TMC-114)","A convenient synthesis of (3R,3aS,6aR)-3-hydroxyhexahydrofuro[2,3-b]furan, a high-affinity nonpeptidal ligand for HIV protease inhibitor UIC-94017, is described. This inhibitor is undergoing advanced clinical trials. The synthesis utilizes a novel stereoselective photochemical 1,3-dioxolane addition to 5(S)-benzyloxymethyl-2(5H)-furanone as the key step. The requisite furanone derivative was prepared in high enantiomeric excess by an immobilized lipase-catalyzed selective acylation of (+/-)-1-(benzyloxy)-3-buten-2-ol and a ring-closing olefin metathesis with Grubbs' catalyst. Optically active bis-THF was converted to protease inhibitor 2 (UIC-94017).",10.1021/jo049156y,2004-10-21,0.639760408855207
Organic Process Research & Development,An Efficient and Cost-Effective Synthesis of Pagoclone,"The compound (+)-2-(7-chloro-1,8-naphthyridin-2-yl)-3 S -(5-methyl-2-oxohexyl)-1-isoindolinone (pagoclone) shows anxiolytic activity due to partial agonism of the benzodiazepine site of the GABA A receptor. We describe the development of an economical and practical process for a 100+ kg pilot plant production used to supply development needs. For the key reaction, a β-keto phosphonium salt was prepared by selectively reacting a primary α-bromo ketone with triphenylphosphine in the presence of a secondary α-bromo ketone. A novel Wittig reaction with a 1-isoindolinone was used to produce racemic pagoclone. The enantiomerically pure drug substance was prepared by hydrolyzing a γ-lactam and resolving the resulting enantiomeric carboxylic acids with (+)-ephedrine hemihydrate. An alternate resolution, involving chiral multicolumn chromatography (MCC) was also developed. The synthesis was completed by a racemization-free lactam formation to afford pagoclone.",10.1021/op034060b,2003-09-17,0.6397592471718984
Organic Letters,"A Unified Strategy for the Syntheses of the Isoquinolinium Alkaloids Berberine, Coptisine, and Jatrorrhizine","Total syntheses of the antibacterial alkaloids berberine, coptisine, and jatrorrhizine have been achieved in four steps through a unified route. The key step of this strategy is an efficient intramolecular Friedel-Crafts alkoxyalkylation which, following oxidation, establishes the isoquinolinium core of these natural products. Herein, the design and development of this synthetic strategy, which has enabled the shortest and most efficient syntheses of these alkaloids reported to date, is described.",10.1021/acs.orglett.8b01702,2018-06-28,0.6397525217631843
Organic Letters,A New Approach to Highly Substituted Cyclopentanoids from a Concise Formal Synthesis of (+)-Roseophilin,"A convergent reaction sequence involving a reductive coupling and a chiral Brønsted acid catalyzed Nazarov reaction is utilized in a concise formal synthesis of (+)-roseophilin (11 steps via longest linear sequence, 10.2% yield, 95% ee).",10.1021/ol300332b,2012-03-28,0.6397326832476236
Angewandte Chemie International Edition,Total Synthesis of TMC‐95A,"A Suzuki–Miyaura coupling reaction to form C1C20, macrolactamization at N9C10, and a mild decarboxylative anti elimination to selectively introduce the (Z)-1-propenylamide are key steps in a highly convergent and completely stereoselective synthesis of the potent proteasome inhibitor TMC-95A (see structure).",10.1002/anie.200351130,2003-06-12,0.6397116855769516
Organic Letters,Total Synthesis of <i>cis</i>-Sylvaticin,"An asymmetric total synthesis of (+)-cis-sylvaticin is described. Key steps include the use of permanganate-mediated oxidative cyclization of 1,5-dienes to synthesize the two major fragments 2 and 3 and a catalytically efficient tethered RCM to unite these THF-containing fragments. In addition, t-BuP 4 base was found to reliably promote rapid alkylation of the butenolide precursor fragment 4.",10.1021/ol800767e,2008-05-20,0.6397030925678819
Journal of Organic Chemistry,Total Synthesis of Amaryllidaceae Alkaloid Buflavine,"A concise synthesis of the amaryllidaceae alkaloid buflavine (1) and its regioisomer (2) involving sequential Meyers' biaryl coupling, enecarbamate formation, and hydrogenation followed by ultimate intramolecular reductive amination is presented.",10.1021/jo0202379,2002-07-04,0.6396970090802138
Tetrahedron,Asymmetric amino-hydroxylation of dienylsilanes. An efficient route to amino-cyclitols,,10.1016/s0040-4039(97)00079-8,1997-02-01,0.639696266399923
Tetrahedron,"Hetero-annulation reaction between 2-acylnaphthoquinones and 2-aminobenzothiazoles. A new synthetic route to antiproliferative benzo[g]benzothiazolo[2,3-b]quinazoline-7,12-quinones",,10.1016/j.tetlet.2015.07.034,2015-07-18,0.639692574233928
Angewandte Chemie International Edition,Asymmetric Total Synthesis of Cytotrienin A: Late‐Stage Installation of C11 Side Chain onto the Macrolactam Scaffold,"Cytotrienin A, an ansamycin-class antibiotic, exhibits potent apoptosis-inducing activity and has attracted much attention as a lead compound for anticancer drugs. Herein, we report a new asymmetric synthetic route to cytotrienin A, employing an unexplored approach involving the late-stage installation of a C11 side chain onto the macrolactam core. In this strategy, we utilized the redox properties of hydroquinone and installed a side chain on the sterically hindered C11 hydroxy group by the traceless Staudinger reaction. This study also demonstrated that the boron-Wittig/iterative Suzuki-Miyaura cross-coupling sequence was effective for the concise and selective construction of the (E,E,E)-conjugated triene moiety. The developed route opens new opportunities for the structure-activity relationship studies of the side chains of these ansamycin antibiotics and the preparation of other synthetic analogs and chemical probes for further biological studies.",10.1002/anie.202303140,2023-05-22,0.6396872802066002
Organic Process Research & Development,Large-Scale Synthesis of a Substituted <scp>d</scp>-Phenylalanine Using Asymmetric Hydrogenation,"A synthetic route to an N -BOC d -phenylalanine pharmaceutical intermediate suitable for rapid scale-up to 150-kg scale was required. A seven-step route based on asymmetric hydrogenation of an N -acetyl dehydroamino-acid was developed. Starting with terephthalic dialdehyde, monoreduction of one aldehyde group, Erlenmeyer condensation, and ring-opening/ O -deacetylation with methanol provided the 4-(hydroxymethyl)-substituted dehydrophenylalanine hydrogenation substrate. Asymmetric hydrogenation of this enamide using [(( R, R )-Ethyl-DuPhos)Rh(COD)]BF 4 proceeded in high enantiomeric excess. Subsequently, the cis -2,6-piperidyl group was introduced by mesylation/displacement, the BOC group was introduced, and acetyl and methyl ester groups were removed by basic hydrolysis. This route was used to manufacture 150 kg of the BOC amino acid 1 .",10.1021/op200129m,2011-08-05,0.6396371676399407
Journal of the American Chemical Society,Total Synthesis of Anti-HIV Agent Chloropeptin I,"A convergent diastereo- and enantioselective total synthesis of anti-HIV agent chloropeptin I is reported. Important features of the total synthesis include: (1) the use of Ti-catalyzed cyanide addition to imines to prepare a requisite amino acid moiety, (2) the discovery of the positive effect of MeOH in the Cu-mediated biaryl ether formation to afford one of the two macrocyclic peptide moieties, and (3) the discovery of the positive influence of collidine in the diastereoselective Pd-mediated cross-coupling to result in efficient formation of another macrocycle within this medicinally important molecule. This key step is performed in the presence of four unprotected phenols, two of which reside on dichlorophenylglycines.",10.1021/ja030249r,2003-07-01,0.6396370350273836
Synthesis,Synthesis of the CDF Ring System of Hexacyclinic Acid,"Abstract Diverse approaches to prepare the nine-membered ring precursor of the DEF fragment of hexacyclinic acid are described, culminating in the synthesis of the CDF ring system of this natural product. The key steps are a Michael addition/elimination sequence and an original intramolecular Tsuji–Trost reaction of an enol with an allylic alcohol.",10.1055/a-2022-1809,2023-01-30,0.6396331349657784
Synthesis,Total Synthesis of Citreochlorol Monochloro Analogues via a Catalytically Enantioselective Carbonyl Allylation,"Abstract An efficient synthetic route to citreochlorol analogues, halogenated polyketide secondary metabolites, is described. The key features are Krische’s enantioselective carbonyl allylation, IBr-promoted cyclization, and regioselective epoxide opening. The importance of the route lies in accessing a versatile epoxy ether that enables the formation of citreochlorol monochloro derivatives.",10.1055/a-1669-0463,2021-10-14,0.6396049363495657
Synlett,"Highly Efficient One-Pot Synthesis of 1,2-Dihydro-2-oxo-3-pyridine-carboxylate Derivatives by FeCl<sub>3</sub>-Promoted [3+3] Annulation","An efficient one-pot synthesis of 1,2-dihydro-2-oxo-3-pyridinecarboxylate derivatives starting from enones and ethyl ­cyanoacetate in moderate to good yields is described. This novel tandem [3+3] annulation method mediated by FeCl3 involves Michael addition and ketone-nitrile annulation followed by aromatization-dehydrogenation. A plausible mechanism is also proposed.",10.1055/s-2005-917092,2005-01-01,0.639590133919666
Organic Letters,Enantioselective Three-Step Synthesis of Homo-β-proline: A Donor–Acceptor Cyclopropane as Key Intermediate,"An enantioselective three-step synthesis of the GABA uptake inhibitor ( S )-(+)-homo-β-proline was developed. The basis for the synthesis was the enantioselective Cu I -catalyzed cyclopropanation of N -Boc-pyrrole, a substrate that persistently has proved to be challenging in such transformations. The cyclopropanation can be performed on a 150 mmol scale, and the two subsequent steps (i.e., hydrogenation and in situ cyclopropane-opening/double-deprotection) toward the target molecule proceed smoothly in quantitative yield without loss of enantiopurity.",10.1021/acs.orglett.7b01111,2017-05-09,0.6395877765506273
European Journal of Organic Chemistry,An Efficient Asymmetric Synthesis of Tarchonanthuslactone,"Abstract An efficient and straightforward ten‐step asymmetric synthesis of the polyketide tarchonanthuslactone ( 1 ) in good overall yield (21% starting from chloro lactone 5 ) and with excellent diastereomeric and enantiomeric excesses ( de , ee ⩾ 96%) is described. The new synthetic route is based on the α,β‐unsaturated δ‐lactone building block 5 , available in enantiopure form ( ee &gt; 99%) through an enzymatic procedure, and its conversion into methyl ketone 11 by an Umpolung strategy. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2003)",10.1002/ejoc.200300412,2003-11-01,0.639569927752798
Journal of Organic Chemistry,A New Synthesis of Neu5Ac from <scp>d</scp>-Glucono-δ-lactone,A new route to Neu5Ac methyl ester (23) with a readily available sugar D-glucono-delta-lactone as starting material has been developed. A diastereoselective propargylation of alpha-acetamino aldehyde and a subsequent KMnO(4) oxidation of the terminal alkyne served as the key steps.,10.1021/jo026056o,2002-08-28,0.6395624969159504
Organic Letters,Total Synthesis of (+)-Aplykurodinone-1,"Starting from (R)-citronellic acid and (R)-seudenol, the total synthesis of (+)-aplykurodinone-1, a highly degraded marine steroid, has been achieved in 11 steps and in 19% overall yield with excellent stereochemical control. In addition to the features such as an Ireland-Claisen rearrangement, an intramolecular carbonyl-ene cyclization, and an intramolecular Michael addition, the present synthetic strategy is accomplished without the use of protecting groups.",10.1021/acs.orglett.7b02350,2017-08-31,0.6395521695218777
Journal of the American Chemical Society,Total Synthesis of Darobactin A,"The collaborative total synthesis of darobactin A, a recently isolated antibiotic that selectively targets Gram-negative bacteria, has been accomplished in a convergent fashion with a longest linear sequence of 16 steps from d-Garner's aldehyde and l-serine. Scalable routes toward three non-canonical amino acids were developed to enable the synthesis. The closure of the bismacrocycle was realized through sequential, halogen-selective Larock indole syntheses, where the proper order of cyclizations proved crucial for the formation of the desired atropisomer of the natural product.",10.1021/jacs.2c05891,2022-07-28,0.6395471980600754
Organic Letters,"An Efficient, Second-Generation Synthesis of the Signature Dioxabicyclo[3.2.1]octane Core of (+)-Sorangicin A and Elaboration of the (<i>Z</i>,<i>Z</i>,<i>E</i>)-Triene Acid System","An efficient, second-generation synthesis of the signature dioxabicyclo[3.2.1]octane core of (+)-sorangicin A (1), in conjunction with an effective, stereocontrolled protocol to arrive at the requisite (Z,Z,E)-triene acid system has been developed. Highlights of the core construction entail a three-component union, a KHMDS-promoted epoxide ring formation-ring opening cascade, a Takai olefination, and a chemoselective Sharpless dihydroxylation. Assembly of the triene acid system was then achieved via Stille cross-coupling with the ethyl ester of (Z,Z)-5-tributylstannyl-2,4-pentadienoic acid, followed by mild hydrolysis preserving the triene configuration.",10.1021/ol802942j,2009-01-30,0.6395447497696153
Organic Letters,Synthesis of Cruentaren A,"Cruentaren A, an antifungal benzolactone produced by the myxobacterium Byssovorax cruenta, is highly cytotoxic against various human cancer cell lines and a highly selective inhibitor of mitochondrial F-ATPase. A convergent and efficient synthesis of cruentaren A is reported, based upon a diastereoselective alkylation, a series of stereoselective aldol reactions utilizing Myers' pseudoephedrine propionamide, an acyl bromide mediated esterification, and a ring-closing metathesis (RCM) as the key steps. The RCM reaction was applied for the first time toward the total synthesis of cruentaren A, which led to a convergent and efficient synthesis of the natural product.",10.1021/ol302999v,2012-12-03,0.639543950123191
Journal of Organic Chemistry,Easy Access to Fully Functionalized Chiral Tetrahydro-β-Carboline Alkaloids,"A four-step synthetic route to fully substituted chiral tetrahydro-β-carbolines (THBCs) is described. Starting from the (R,S,S)-Friedel-Crafts/Henry adduct obtained from three-component coupling of an indole, nitroalkene, and aldehyde catalyzed by imidazoline-aminophenol-CuOTf, the (1S,3S,4R)-THBCs were readily synthesized in a three-step operation including reduction of the nitro-functionality and Pictet-Spengler cyclization.",10.1021/jo1025833,2011-03-04,0.6395242921495771
Synthesis,Studies on the Total Synthesis of Antibiotic Macrolactin S: A Conventional Approach for the Synthesis of the C1–C9 and C10–C24 Fragments,"The C1–C9 and C10–C24 segments of the 24-membered polyene macrolide macrolactin S were synthesized by routes involving an epoxide-ring-opening reaction, an Ohira–Bestmann alkyne formation, a chelation-controlled nucleophilic addition reaction, and a Still–Gennari olefination as key steps. A chiron approach , starting from readily available glucose diacetonide, was used to synthesize a key intermediate, and a convergent approach was adopted for the synthesis of the key C10–C24 fragment.",10.1055/s-0036-1589132,2017-11-16,0.6395236371184002
Tetrahedron,New synthesis of the cyclic tetrapeptide tentoxin employing an azlactone as key intermediate,,10.1016/0040-4039(95)00762-2,1995-06-01,0.6395202858940026
Journal of Organic Chemistry,Total Synthesis of Spirotenuipesines A and B,"Spirotenuipesines A and B, isolated from the entomopathogenic fungus Paecilomyces tenuipes by Oshima and co-workers, have been synthesized. The synthesis features the highly stereoselective construction of two vicinal all-carbon quaternary centers (C(5) and C(6)) via an intramolecular cyclopropanation/radical initiated fragmentation sequence and a diastereoselective intermolecular Diels-Alder reaction between alpha-methylenelactone dienophile 20 and synergistic diene 6a. Installation of the C(9) tertiary alcohol occurred via nucleophilic methylation. An RCM reaction to produce a tetrasubstituted double bond in the presence of free allylic alcohol and homoallylic oxygenated functional group is also described. This route shortened the synthesis of 11 from 9 steps to 3 steps. We have further developed a strategy to gain access to optically active spirotenuipesines A and B through the synthesis of enantioenriched 10 from commercially available R-(-)-epichlorohydrin.",10.1021/jo8016814,2008-10-31,0.6395007303624252
Tetrahedron,A chemoselective hydroxymethylation: new route for the synthesis of 6-aroyl-4-(4H-triazol-3-yl)thiomorpholin-3-ones,,10.1016/j.tetlet.2011.12.100,2011-12-30,0.6394961745772074
Angewandte Chemie International Edition,Bioinspired Asymmetric Synthesis of Hispidanin A,"The first enantiospecific synthesis of hispidanin A (4), a dimeric diterpenoid from the rhizomes of Isodon hispida, was achieved with a longest linear sequence of 12 steps in 6.5 % overall yield. A key component is the use of the abundant and naturally occurring diterpenoids (+)-sclareolide and (+)-sclareol as starting materials, which enables the gram-scale preparation of the key intermediates totarane (1) and s-trans-12E,14-labdadien-20,8β-olide (2). Subsequently a thermal or an erbium-catalyzed intermolecular Diels-Alder reaction of totarane (1) with labdadienolide (2) provide convergent and rapid access to the natural product hispidanin A (4). The synthetic studies have offered significant impetus for the efficient construction of these architecturally complex natural products.",10.1002/anie.201700838,2017-03-23,0.6394661573253765
Angewandte Chemie International Edition,Total Synthesis of the Monoterpenoid Indole Alkaloid (±)‐Aspidophylline A,"Abstract Aspidophylline A belongs to the akuammiline alkaloid family, the members of which possess intriguing cagelike structures and diverse biological activities. Herein we report a 15‐step synthesis of this alkaloid from conveniently available starting materials. The key elements of the synthesis include an intramolecular oxidative coupling to create the tetracyclic furoindoline motif of the natural product and a [Ni(cod) 2 ]‐mediated cyclization to install its piperidine ring.",10.1002/anie.201310928,2014-01-31,0.6394570744307351
Organic Letters,Total Synthesis of the Cyclic Heptapeptide Argyrin B:  A New Potent Inhibitor of T-Cell Independent Antibody Formation,[structure: see text] The total synthesis of Argyrin B (1) is presented using a synthetic plan that is convergent and flexible and conserves the stereogenic centers. The unusual amino acid 4-methoxy tryptophan (6) was obtained via an enzymatic resolution. Cyclization followed by oxidative elimination of the phenylseleno cysteine to the sensitive dehydroalanine afforded synthetic 1.,10.1021/ol017184m,2002-02-05,0.6394565866452475
Organic Letters,Total Synthesis of (−)-Sigillin A: A Polychlorinated and Polyoxygenated Natural Product,"The total synthesis of (−)-sigillin A, a highly chlorinated and oxygenated octahydroisocoumarin, is described herein. A hexahydroisocoumarin skeleton was constructed from ( R )-4-(trichloromethyl)oxetan-2-one in seven steps. Its unique manganese oxidation provided an enone as the key intermediate of sigillin A. Stereoselective installation of two hydroxy groups and formation of gem -dichloroalkene from the corresponding ketone led to the total synthesis of (−)-sigillin A in a total of 16 steps.",10.1021/acs.orglett.0c02930,2020-09-16,0.6394531128457768
Synlett,A Novel Synthetic Route to α-Galactosyl Ceramides and iGb3 Using DTBS-Directed α-Selective Galactosylation,"A novel synthetic route to α-galactosyl ceramides and isoglobotrihexosylceramide (iGb3), which can activate NKT cells, was developed by exploiting a di-tert-butylsilylene-directed α-selective galactosylation procedure.",10.1055/s-2006-949649,2006-09-01,0.6394462800145698
Tetrahedron,A simple and efficient route to the FKBP-binding domain from rapamycin,,10.1016/j.tetlet.2011.07.094,2011-07-29,0.6394355609611039
Organic Letters,"An Approach to 3,6-Disubstituted 2,5-Dioxybenzoquinones via Two Sequential Suzuki Couplings. Three-Step Synthesis of Leucomelone","Two sequential Suzuki coupling reactions have been developed for efficient synthesis of synthetically and biologically important 3,6-disubstituted 2,5-dioxybenzoquinone architectures in a highly chemoselective controlled manner. The method serves as a key step in the total synthesis of leucomelone in three steps and in 61% overall yield.",10.1021/ol802645f,2009-01-08,0.6394326709303044
Journal of Organic Chemistry,"Unified Total Synthesis, Stereostructural Elucidation, and Biological Evaluation of Sarcophytonolides","Sarcophytonolides are cembranolide diterpenes isolated from the soft corals of genus Sarcophyton . Unified total synthesis of sarcophytonolides C, E, F, G, H, and J and isosarcophytonolide D was achieved. The synthetic routes feature NaHMDS- or SmI 2 -mediated fragment coupling, alkoxycarbonylallylation, macrolactonization, and transannular ring-closing metathesis. These total syntheses led to the absolute configurational confirmation of sarcophytonolide H, elucidation of sarcophytonolides C, E, F, and G, and revision of sarcophytonolide J and isosarcophytonolide D. We also evaluated the antifouling activity and toxicity of the synthetic sarcophytonolides H and J and their analogues as well as the cytotoxicity of the synthetic sarcophytonolides and the key synthetic intermediates.",10.1021/acs.joc.8b01634,2018-08-09,0.6394325306013422
Organic Letters,Total Synthesis of Selaginpulvilin C and D Relying on<i>in Situ</i>Formation of Arynes and Their Hydrogenation,The total syntheses of selaginpulvilins C and D is described. The key strategy for the construction of the core fluorene moiety involves in situ formation of an aryne intermediate followed by its formal hydrogenation. The precursor tetraynes that undergo aromatization via hexadehydro Diels-Alder reaction were prepared from readily available building blocks through typical alkyne-coupling reactions.,10.1021/acs.orglett.6b03241,2016-11-18,0.6393980886154432
Angewandte Chemie International Edition,Asymmetric Allylboration of <i>vic</i>‐Tricarbonyl Compounds: Total Synthesis of (+)‐Awajanomycin,To the core: An efficient total synthesis of (+)-awajanomycin was achieved starting with an asymmetric allylboration of a vic-tricarbonyl compound (see scheme; TES=triethylsilyl). A stereoselective alkene dihydroxylation followed by a differentiation of diastereotopic ester groups and a subsequent lactamization gave the bicyclic core structure.,10.1002/anie.201103679,2011-07-14,0.6393872957591338
Organic Letters,Enantioselective Synthesis of (−)-Acetylapoaranotin,"The first enantioselective total synthesis of the epipolythiodiketopiperazine (ETP) natural product (-)-acetylapoaranotin (3) is reported. The concise synthesis was enabled by an eight-step synthesis of a key cyclohexadienol-containing amino ester building block. The absolute stereochemistry of both amino ester building blocks used in the synthesis is set through catalytic asymmetric (1,3)-dipolar cycloaddition reactions. The formal syntheses of (-)-emethallicin E and (-)-haemotocin are also achieved through the preparation of a symmetric cyclohexadienol-containing diketopiperazine.",10.1021/acs.orglett.7b00418,2017-03-28,0.6393680462222037
Organic Letters,"Enantioselective Syntheses of Colletodiol, Colletol, and Grahamimycin A","[reaction: see text] The enantioselective synthesis of colletodiol has been achieved in 11 steps from methyl 1,3,5-octatrienoate and 16 total steps from both ethyl sorbate and methyl 1,3,5-octatrienoate. The route relies upon an enantio- and regioselective Sharpless dihydroxylation and a palladium-catalyzed reduction to form a 5-hydroxy-1-enoate and an 7-hydroxy-1,3-dienoate. These esters were further functionalized, coupled, and macrolactonized to provide colletodiol after deprotection. Grahamimycin A and colletol were synthesized in one and two steps, respectively, from colletodiol.",10.1021/ol0269502,2002-11-16,0.6393666975269298
Synlett,Preparation of a Key Tricyclic Intermediate for the Synthesis of Pyrroloiminoquinone Natural Products,All articles of this category Indole 12 was prepared in seven steps from para-anisidine. The key step was an intramolecular nucleophile aromatic substitution reaction.,10.1055/s-1998-867117,1998-08-01,0.6393612063233848
Journal of the American Chemical Society,"Total Synthesis of (−)-Penifulvin A, an Insecticide with a Dioxafenestrane Skeleton","Herein we report the first total synthesis of Penifulvin A, a sesquiterpenoid with a novel dioxa-fenestrane structure. Penifulvin A is a potent insecticide against the fall armyworm Spodoptera frugiperda which causes enormous damage in the US by consuming foliage of a variety of field crops. A five-step racemic and an eight-step enantioselective route to the natural product and the determination of its absolute configuration are described. The key step involves a meta-photocycloaddition, giving rapid access to the carbon skeleton of penifulvin A in a stereoselective fashion. Finally an oxidation cascade leads to the natural product. The synthetic route is free from protecting groups, scalable, and flexible so that a variety of analogues, among them penifulvins B-E, should be available for performing SAR tests in the insecticidal role.",10.1021/ja8083048,2008-12-19,0.6393532751284943
Tetrahedron,"A new route to the versatile synthesis of thiopyrano[2,3-b:6,5-b′]diindoles via 2-(alkylthio)-indole-3-carbaldehydes",,10.1016/j.tetlet.2014.08.100,2014-08-29,0.6393507968515908
Journal of Organic Chemistry,A Stereoselective Synthesis of (±)-C-Secolimonoid BCDE Model Compounds Related to the Insect Antifeedant Ohchinolide,"A short and stereoselective synthesis of a (+/-)-BCDE C-secolimonid model insect antifeedant related to ohchinolide and nimbolidin was accomplished in 13 (30% overall yield) and 15 (30% overall yield) steps, respectively, from ethyl drimanate. The key steps are the torquoselective electrocyclization of the divinyl ketone 6, induced by perchloric acid, and the stereoselective rearrangement of the hydroxy lactone 12, inspired in a biosynthetic proposal. An alternative route, which provides access to (+/-)-BCDE ohchinolide and nimbolidin isomers, is also described.",10.1021/jo010449q,2001-10-13,0.6393441549023663
European Journal of Organic Chemistry,Application and Scope of Schreiber's Gold(I)‐Catalyzed α‐Pyrone Synthesis to Ring A Aromatic Podolactones,"Abstract Schreiber's gold(I)‐catalyzed synthesis of α‐pyrones was adapted to the total synthesis of a ring A aromatic podolactone, urbalactone. The scope of the acetylenic ester partner in the formation of α‐pyrones was studied. The total synthesis features, as key steps, α‐pyrone formation, Friedel–Crafts cyclization, Stille coupling, and a N , N′ ‐dicyclohexylcarbodiimide/4‐( N , N ‐dimethylamino)pyridine lactonization to generate the γ‐lactone. Several α‐pyrone intermediates from this work exhibited in vitro antiproliferative activity against the A2780 ovarian cancer cell line.",10.1002/ejoc.201402803,2014-07-22,0.6393380271482482
Tetrahedron,"Milbemycin synthesis: synthesis of 6β-hydroxy-3,4-dihydromilbemycin E",,10.1016/s0040-4039(00)79699-7,1991-05-01,0.6393323734077524
Organic Letters,A Stereoselective Synthesis of (+)-Herboxidiene/GEX1A,"A stereoselective synthesis of (+)-herboxidiene is described. The convergent synthesis utilized a Suzuki cross-coupling reaction to assemble the key segments. The synthesis of the functionalized tetrahydropyran ring utilized an Achmatowicz reaction as the key step. The synthesis of the C10-C19 segment was accomplished using Brown's crotylboration, asymmetric alkylation, and a stereoselective allylic chlorination reactions.",10.1021/ol102549a,2010-12-02,0.6393307678260902
Journal of Organic Chemistry,"Synthesis of 2,4-Diaminoquinazolines and Tricyclic Quinazolines by Cascade Reductive Cyclization of Methyl <i>N</i>-Cyano-2-nitrobenzimidates","An efficient route to N(4)-substituted 2,4-diaminoquinazolines has been developed by employing tandem condensation of cyanoimidate-amine and reductive cyclization in iron-HCl system. This method is tolerant of a following intramolecular N-alkylation and produces two fused heterocycles in a one-pot procedure. This protocol is a facile two-step synthesis of tricyclic quinazolines, which is effected by potent cyanoimidation and tandem reductive cyclization from 2-nitrobenzaldehydes. Moreover, the forming process of tricyclic quinazolines has been investigated from the ring-opening/ring-closing cascade point of view. It is found that the preparation of tricyclic quinazolinones in good yields relies on the selective hydrolysis of tricyclic quinazolines in base or acid system.",10.1021/jo2023697,2012-01-27,0.6392998135246825
Journal of the American Chemical Society,Total Synthesis of Isomalabaricane Triterpenoids,"The first total syntheses of (±)-rhabdastrellic acid A and (±)-stelletin E, highly cytotoxic isomalabaricane triterpenoids, have been accomplished in a linear sequence of 14 steps from commercial geranylacetone. The exceptionally strained trans-syn-trans- perhydrobenz[ e ]indene core characteristic of the isomalabaricanes is efficiently accessed in a selective manner through a rapid, complexity-generating sequence. This process features a reductive radical polyene cyclization, an unprecedented oxidative Rautenstrauch cycloisomerization, and umpolung α-substitution of a p -toluenesulfonylhydrazone with in situ reductive transposition. A late-stage cross-coupling in concert with a modular approach to polyunsaturated side chains renders this a general strategy for the synthesis of numerous family members of these synthetically challenging and hitherto inaccessible marine triterpenoids.",10.1021/jacs.9b08487,2019-08-26,0.6392957272832991
Tetrahedron,"A new asymmetric route to substituted piperidines: synthesis of N-alkyl-3,4-dihydroxy-5-alkylpiperidines",,10.1016/s0040-4039(00)00267-7,2000-04-01,0.6392918667526846
Journal of Organic Chemistry,Enantiospecific Entry to a Common Decalin Intermediate for the Syntheses of Highly Oxygenated Terpenoids,"Herein, we describe an enantiospecific route to one enantiomer of a common decalin core that is present in numerous highly oxygenated terpenoids. This intermediate is accessed in eight steps from ( R )-carvone, an inexpensive, enantioenriched building block, which can be elaborated to the desired bicycle through sequential Fe(III)-catalyzed reductive olefin coupling and Dieckmann condensation. The same synthetic route may be applied to ( S )-carvone to afford the enantiomer of this common intermediate for other applications.",10.1021/acs.joc.9b01937,2019-08-27,0.6392884342598978
Journal of Organic Chemistry,An Efficient and Enantioselective Approach to the Azaspirocyclic Core of Alkaloids:  Formal Synthesis of Halichlorine and Pinnaic Acid,"A novel, highly stereoselective synthesis of an azaspirocyclic core, which contains four stereogenic carbons consistent with structures of natural halichlorine and pinnaic acid, is presented. Lipase PS-catalyzed selective acylation, asymmetric methylation on the alpha-methylene of the bicyclic lactone, and an asymmetric Michael addition of the tertiary nitro cyclopentane were concisely used to conquer the challenging problem of successfully constructing the C9 quarternary carbon center with complete stereocontrol. The spiropiperidine ring was formed by reduction of the delta-nitroketone, intramolecular condensation, and then highly stereoselective reduction of the cyclic nitrone with NaBH(4). This spirocyclic core is a key intermediate in Danishefsky's synthesis of pinnaic acid and halichlorine.",10.1021/jo047882v,2005-05-26,0.6392819012997323
Journal of Organic Chemistry,"Synthesis of Nonracemic 1,4-Benzoxazines via Ring Opening/Cyclization of Activated Aziridines with 2-Halophenols: Formal Synthesis of Levofloxacin","Novel 3,4-dihydro-1,4-benzoxazine derivatives have been synthesized by an efficient and simple method in excellent enantio- and diastereospecificity (ee > 99%, de > 99%). The reaction proceeds via Lewis acid-catalyzed S N 2-type ring opening of activated aziridines with 2-halophenols followed by Cu(I)-catalyzed intramolecular C–N cyclization in a stepwise fashion under one-pot conditions to furnish the 3,4-dihydro-1,4-benzoxazine derivatives in excellent yields (up to 95%). The strategy offers a short and efficient synthesis to ( S )-3-methyl-1,4-benzoxazine ( S )- 3v, a late stage intermediate in the synthesis of levofloxacin.",10.1021/acs.joc.8b00788,2018-06-04,0.6392445162484118
European Journal of Organic Chemistry,Stereoselective Synthesis ofcarba- andC-Glycosyl Analogs of Fucopyranosides,"Fucopyranoside analogs with methylene groups instead of endo- or exo-anomeric oxygens, carba- and C-fucopyranosides, respectively, were synthesized. For the synthesis of 5a-carba-L-fucose (1) two approaches were studied, which shared a common cyclitol building block (8), obtained from a SmI2-promoted carbocyclization of a D-mannitol derivative. The first route made use of a Stork radical cyclization onto a conduritol derivative 13 as the key step, which failed to give the silyl ether ring. The second route furnished the target 1, and involved regioselective elimination of a cyclic sulfate 9, and stereoselective hydrogenation of a double bond, controlled by substitution on the substrate. For the synthesis of 1-C-fucopyranosides (37, 38, and 42) a new method based on the use of fucosyl phenyl sulfoxides (35 and 41) was employed. An anomeric carbanion is generated through phenylsulfinyl-lithium exchange, which reacted with electrophiles with retention of configuration at the anomeric center. The required fucosyl sulfoxides were prepared from L-fucose by highly stereoselective thioglycosylation reactions.",10.1002/1099-0690(200004)2000:7<1285::aid-ejoc1285>3.0.co;2-z,2000-04-01,0.6392387204828068
Organic Process Research & Development,A Facile Total Synthesis for Large-Scale Production of Imatinib Base,"An efficient, economic process has been developed for the production of imatinib with 99.99% purity and 50% overall yield from four steps. Formation and control of all possible impurities is described. The synthesis comprises the condensation of N -(5-amino-2-methylphenyl)-4-(3-pyridinyl)-2-pyrimidineamine with 4-(4-methylpiperazinomethyl)benzoyl chloride in isopropyl alcohol solvent in the presence of potassium carbonate to yield imatinib base.",10.1021/op300212u,2012-10-16,0.639209557095418
Tetrahedron,"An efficient synthesis of a key intermediate for optically active 5,6--carbapenem antibiotics",,10.1016/s0040-4039(00)83870-8,1986-01-01,0.639207165231217
Journal of Organic Chemistry,Carbocyclic Nucleoside Analogs. 1. Concise Enantioselective Synthesis of Functionalized Cyclopentanes and Formal Total Synthesis of Aristeromycin,"An enantioselective synthesis of functionalized cyclopentanes has been used to access carbocyclic nucleoside analogs. This pathway allows access to carbocyclic C - or carbocyclic N -nucleosides from a common intermediate, ester 16 . Additionally, (1 R,2 R,3 S,4 R )-4-amino-2,3-dihydroxy-1-cyclopentanemethanol ( 18 ), an intermediate in the total synthesis of aristeromycin, has been prepared as a single enantiomer in eight isolated steps from cyclopentadiene. Progress toward the synthesis of novel carbocyclic C -nucleosides is also discussed.",10.1021/jo970153d,1997-06-13,0.6391718471283794
Organic Letters,Total Synthesis of (−)-Agelastatin A,"A new route to (-)-agelastatin A is reported. The requisite nitrogen functionalities of the agelastatin core have been installed by intramolecular aziridination of an azidoformate and subsequent regioselective azidation, leading to net trans-diamination of the double bond. The present synthesis also demonstrates two new protocols for the preparation of an imidazolidinone hemiaminal motif from an oxazolidinone intermediate which comprise sequential N-tert-butoxycarbonylation, urea formation, hydrolysis, and oxidative cyclization, and direct aminolysis and subsequent oxidative cyclization.",10.1021/ol802225g,2008-11-12,0.6391278760396227
Journal of Organic Chemistry,Short Synthesis of Alkaloid (−)-205B,"The alkaloid (−)-205B has in the past served as a testing ground for novel approaches in nitrogen heterocycle synthesis. We herein report a highly straightforward synthesis of (−)-205B in just six synthetic steps, making it the shortest route currently known. The central steps of our approach are a vinylogous Mukaiyama–Mannich reaction to establish the first two stereogenic centers with excellent diastereo- and enantiocontrol followed by zinc-mediated Barbier allylation to set the third chiral center with high substrate control. Upon cyclization of the Barbier product to lactam and enolate methylation, the third ring is annulated by a one-pot sequence of lactam reduction and aza-Prins cyclization to directly set the final stereogenic center with complete cis -stereoselectivity. As the iminium ion undergoing the aza-Prins cyclization rapidly isomerized to a planar enamine intermediate, the alkaloid was eventually obtained as a 1:1 mixture of C6 diastereomers, which were readily separated by chromatography. Yet, the target natural product was obtained isomerically pure in an overall yield of 12%, which compares favorably with all previous syntheses.",10.1021/acs.joc.0c01885,2020-09-03,0.639123913302656
Synlett,A New Route to Model Insect Antifeedants Related to Azadiradione Via Cationic Electrocyclization,"All articles of this category Starting from citral, a concise and efficient synthesis of the model insect antifeedant 9 based on the C, D and E rings of the limonoid azadiradione has been achieved. The key step involves a selective and unusual Nazarov cyclization of 4 to close the five-membered ring thus to assemble the carbon framework, followed by Lewis acid-induced dyotropic rearrangement of the epoxide 7 to set the required alpha-furan stereochemistry in the target compound. Synthesis - antifeedant - limonoids - azadiradione - cationic electrocylization",10.1055/s-1995-4989,1995-05-01,0.6391096102406312
Tetrahedron,A novel synthetic route to 6-oxabicyclo[3.1.1]heptane skeleton,,10.1016/s0040-4039(00)77407-7,1980-01-01,0.6391095736670943
Tetrahedron,Synthesis of a novel HMG-COA reductase inhibitor,,10.1016/s0040-4039(00)82484-3,1988-01-01,0.6391070824942825
Organic Process Research & Development,An Improved Synthesis of 4-(1-Piperazinyl)benzo[<i>b</i>]thiophene Dihydrochloride,"2-Chloro-6-fluorobenzaldehyde was converted to 4-(1-piperazinyl)benzo[ b ]thiophene dihydrochloride ( 18 ), an intermediate in the synthesis of brexpiprazole, via a five-step sequence in 54% overall yield. This procedure requires no expensive catalyst and avoids the side products produced in the coupling step in the reported process. Several kilograms of compound 18 were prepared using this economical and scalable process.",10.1021/acs.oprd.5b00027,2015-03-12,0.6391003921713474
Synlett,Enantioselective Synthesis of 2-Azido-norfuranomycin from a d-Glucose-Derived Chiral Synthon,"Abstract The enantioselective synthesis of 2-azido-norfuranomycin (11) was accomplished from a d-glucose-derived chiral synthon (4). The absolute configuration at C3 and C4 of synthon 4 corresponds to that of the target molecule, confirming its utility in asymmetric synthesis. Key steps include 1,2-acetonide hydrolysis, oxidative cleavage (NaIO₄), reduction to a 2-azido-3-hydroxy olefin precursor, and ring-closing metathesis (RCM) to form the 3′,4′-dihydrofuran core. The method provides 2-azido-norfuranomycin in high yield and enantiopurity from readily available carbohydrate starting materials. A similar attempt was undertaken to obtain 2-azido-furanomycin 12.",10.1055/a-2733-2114,2025-10-27,0.6390962819419789
Journal of Organic Chemistry,Formal Total Synthesis of (+)-Diepoxin σ,The highly oxygenated antifungal anticancer natural product (+/-)-diepoxin sigma was prepared in 10 steps and in 15% overall yield from O-methylnaphthazarin. Highlights of the synthetic work include an Ullmann coupling and a possibly biomimetic oxidative spirocyclization for the introduction of the naphthalene ketal as well as the use of a retro-Diels-Alder reaction to unmask the reactive enone moiety in the naphthoquinone bisepoxide ring system. A novel highly bulky chiral binaphthol ligand was developed for a boron-mediated Diels-Alder reaction that constitutes a formal asymmetric total synthesis of (+)-diepoxin sigma.,10.1021/jo000684t,2000-09-09,0.6390642592376227
Journal of Organic Chemistry,Total Synthesis and Revision of C6 Stereochemistry of (+)-Amphidinolide W,"An enantioselective first total synthesis and structural revision of the cytotoxic natural product amphidinolide W is described. We initially investigated a ring-closing metathesis based synthetic strategy to form the 12-membered macrocycle. This strategy was unsuccessful as it led to formation of a 17-membered macrocycle. Subsequently, we explored an alternative strategy that involved cross-metathesis followed by a Yamaguchi macrolactonization reaction sequence utilizing the same key intermediates. This strategy led to the synthesis of amphidinolide W. The synthesis was carried out in a convergent manner, and four of the five stereogenic centers in amphidinolide W were set by asymmetric synthesis. The synthesis features Sharpless asymmetric dihydroxylation, diastereoselective alkylation, efficient cross-metathesis of functionalized substrates, and novel functional group transformations using selective lipase-catalyzed hydrolysis of the primary acetate group. Of particular note, the C6 absolute stereochemistry of amphidinolide W has now been revised through our synthesis.",10.1021/jo052181z,2005-12-24,0.6390555901273356
Journal of Organic Chemistry,Synthesis of Bridged Azabicyclic Structures via Ring-Closing Olefin Metathesis,"A new strategy for the facile synthesis of azabicyclo[m.n.1]alkenes (m = 3-5; n = 3, 2) has been developed that involves the ring-closing metathesis (RCM) reaction of cis-2,6-dialkenyl-N-acyl piperidine derivatives. The requisite 2,6-dialkenylpiperidines may be readily prepared in six steps starting from glutarimide (11) or three steps from 4-methoxypyridine (25). In one example that establishes the practical utility of the procedure, the functionalized 8-azabicyclo[3.2.1]octane 32, which is a potential intermediate for the syntheses of various tropane alkaloids, was prepared. Additionally, a new route for the construction of the bridged tetrahydro-beta-carboline ring system 5 has been developed that features the ring-closing metathesis of the enyne 45 to construct the bridging ring in 46. This concise route to 46 also features a potentially general and useful procedure for the one-step preparation of a terminal alkyne from an ester function. Selective oxidation of the vinyl group in 46 afforded the unsaturated aldehyde 47, which may serve as a useful intermediate in syntheses of several Sarpagine alkaloids.",10.1021/jo0349936,2003-10-18,0.6390438376775354
Organic Letters,Asymmetric Synthesis of (+)-Vellosimine Enabled by a Sequential Nucleophilic Addition/Cyclization Process,"Herein, we achieved the asymmetric synthesis of (+)-vellosimine in 13 steps (longest linear sequences, LLS). This synthesis featured a sequential nucleophilic addition/cyclization process, which provided an efficient protocol for synthesizing a range of indole fused azabicyclo[3.3.1]nonane. Additionally, a SmI 2 -mediated reductive cyclization of ketone with an attached α,β-unsaturated ester for constructing the strained quinuclidine moiety was also highlighted.",10.1021/acs.orglett.3c03170,2023-11-13,0.6390367640436297
Tetrahedron,"One-step synthesis of diazadihydroacenaphthylene derivatives with an isoxazoline ring, starting from 1-benzylamino-1-methylsulfanyl-2-nitroethenes",,10.1016/j.tetlet.2006.03.003,2006-03-25,0.6390072848092979
Synlett,"Stereoselective Synthesis of 4-Acetylamino-2,4,6-trideoxy-L-<i>ribo</i>-hexose from Ethyl (<i>S</i>)-β-Hydroxybutyrate","All articles of this category The title protected aminosugar 11 was stereoselectively prepared in 14 steps and 8% overall yield from L- allo -threonine synthetic equivalent 2 , which is in turn obtained in one step from ethyl ( S )-ß-hydroxvbutyrate.",10.1055/s-1992-21351,1992-01-01,0.6389984619703537
Journal of Organic Chemistry,Synthesis of 1-<i>tert</i>-Butyl-4-chloropiperidine:  Generation of an <i>N</i>-<i>tert</i>-Butyl Group by the Reaction of a Dimethyliminium Salt with Methylmagnesium Chloride,"Two efficient routes to 1-tert-butyl-4-chloropiperidine are described. In the first route, the key thionyl chloride mediated chlorination reaction features the use of tetrabutylammonium chloride as an additive that effectively suppresses the formation of an elimination-derived side product. In the second route, a novel alternative synthesis of 1-tert-butyl-4-chloropiperidine was developed in which the tertiary butyl group on the nitrogen is efficiently generated through the addition of methylmagnesium chloride to a dimethyliminium salt in 71% overall yield.",10.1021/jo048047g,2005-02-01,0.6389911018566972
Angewandte Chemie International Edition,Total Synthesis of Enzyme Inhibitor Spirastrellolide A—Stereochemical Confirmation,Problem solved: Spirastrellolide A methyl ester (see picture) is a potent phosphatase 2A inhibitor and has been the subject of considerable synthetic interest since its isolation in 2003. Paterson and co-workers have now succeeded in the total synthesis of this compound by using a flexible modular strategy. This total synthesis and previous studies towards fragments for spectroscopic comparison and stereochemical determination is summarized.,10.1002/anie.200800486,2008-03-17,0.6389713140483884
Tetrahedron,Convergent synthesis of the IJKLM-ring part of ciguatoxin CTX3C,,10.1016/j.tetlet.2005.09.164,2005-10-18,0.6389695271830946
Tetrahedron,Convergent synthesis of the FGHI ring segment of yessotoxin,,10.1016/j.tetlet.2005.10.136,2005-11-11,0.6389695271830946
Tetrahedron,Convergent synthesis of the F–K ring segment of brevetoxin B,,10.1016/j.tetlet.2003.09.003,2003-10-01,0.6389695271830946
Tetrahedron,Convergent synthesis of the A–F ring segment of yessotoxin and adriatoxin,,10.1016/j.tetlet.2003.10.010,2003-11-14,0.6389695271830946
Tetrahedron,Convergent synthesis of the ABCDE-ring part of ciguatoxin CTX3C,,10.1016/j.tetlet.2004.07.145,2004-08-27,0.6389695271830946
Journal of the American Chemical Society,Enantioselective Construction of Cyclobutanes: A New and Concise Approach to the Total Synthesis of (+)-Piperarborenine B,"A highly diastereoselective and enantioselective Cu(II)/SaBOX-catalyzed [2 + 2] cycloaddition of methylidenemalonate and multisubstituted alkenes was developed to furnish optically active cyclobutanes in high yields with >99/1 dr and up to >99% ee. By application of the newly developed method, the total synthesis of (+)-piperarborenine B was completed in eight steps from methylidenemalonate and olefin in 17% overall yield with >99/1 dr and 99% ee.",10.1021/jacs.6b08279,2016-09-08,0.6389635733926335
European Journal of Organic Chemistry,A New Synthetic Approach to Dioxoaporphines − Application to the Synthesis of N-Methylouregidione,"A convenient and versatile short-step synthesis of dioxoaporphines, illustrated by the first total synthesis of the alkaloid N-methylouregidione (1c), is described.",10.1002/1099-0690(200107)2001:13<2559::aid-ejoc2559>3.0.co;2-3,2001-07-01,0.6389544156447791
Tetrahedron,An approach to the synthesis of the naphthyridinomycin alkaloids: The synthesis of two subunits,,10.1016/s0040-4039(01)81394-0,1984-01-01,0.6389279592002952
Organic Letters,"Asymmetric Total Synthesis of Bacillariolide III, a Marine Oxylipin","[reaction: see text] The asymmetric total synthesis of bacillariolide III has been achieved via 15 linear steps in 14.6% overall yield. The key feature of this synthetic route involves the highly stereoselective construction of the vinyl-substituted bicyclic lactone by an intramolecular Pd(0)-catalyzed allylic alkylation and its facile conversion to the hydroxy bicyclic lactone skeleton of bacillariolide III, induced by stereoselective vinylcerium addition to the aldehyde. In addition, the (Z)-pentenoic acid was efficiently introduced by the internal hydroxy group tethered ring-closing metathesis (RCM).",10.1021/ol0363366,2004-01-14,0.6389265900903431
Organic Letters,First Total Synthesis of Hinckdentine A,"We have accomplished the first total synthesis of (+/-)-hinckdentine A (1). The key steps are m-CPBA oxidation of 2-arylindole followed by acid-mediated Mannich-type C-C bond formation of 2-hydroxyindolin-3-one, seven-membered ring closure, and regioselective tribromination.",10.1021/ol802394n,2008-12-04,0.638921339444272
Journal of Organic Chemistry,"First Total Synthesis of an Exceptionally Potent Antitumor Saponin, OSW-1","OSW-1 (1), an acylated disaccharide cholestane saponin from Ornithogalum saudersiae with exceptionally potent antitumor activity, was first synthesized from commercially available dehydroisoandrosterone, L-arabinose, and D-xylose in total 27 steps with the longest linear sequence of 14 steps and in 6% yield.",10.1021/jo981685c,1998-12-15,0.6389139622976712
Journal of the American Chemical Society,Concise Enantioselective Synthesis of ent-Malbrancheamide B,"A concise enantioselective synthesis of the fungal metabolite ent-malbrancheamide B was accomplished through the union of a C-prenylated proline derivative and a substituted indole pyruvic acid SEM enol ether, followed by a cationic double cyclization as the key step.",10.1021/ja900688y,2009-03-10,0.6389005964297103
Tetrahedron,"Synthesis of 2,6-anhydro-3-deoxy-5-O-phosphono-3-tetradecanamido-4-O-[(R)-3-(tetradecanoyloxy)tetradecanoyl]-d-glycero-d- ido-heptonic acid as a new potent endotoxin antagonist and its dimeric analogue",,10.1016/0040-4039(96)01646-2,1996-09-01,0.6388918114341148
Synthesis,"Total Synthesis of d-lyxo-Phytosphingosine and Formal Synthesis of Pachastrissamine via a Chiral 1,3-Oxazine","Concise and efficient syntheses of d - lyxo -phytosphingosine and pachastrissamine were achieved utilizing a chiral oxazine. The key features in these strategies are the stereoselective intramolecular oxazine formation catalyzed by palladium(0), and intermolecular olefin cross-metathesis.",10.1055/s-0031-1289813,2012-06-26,0.638874936419695
Journal of the American Chemical Society,Asymmetric Total Syntheses of Schizozygane Alkaloids,"The concise, collective, and asymmetric total syntheses of four schizozygane alkaloids, which feature a ""Pan lid""-like hexacyclic core scaffold bearing up to six continuous stereocenters, including two quaternary ones, are described. A new method of dearomative cyclization of cyclopropanol onto the indole ring at C2 was developed to build the ABCF ring system of the schizozygane core with a ketone group. Another key skeleton-building reaction, the Heck/carbonylative lactamization cascade, ensured the rapid assembly of the hexacyclic schizozygane core and concurrent installation of an alkene group. By strategic use of these two reactions and through late-stage diversifications of the functionalized schizozygane core, the first and asymmetric total syntheses of (+)-schizozygine, (+)-3-oxo-14α,15α-epoxyschizozygine, and (+)-α-schizozygol and the total synthesis of (+)-strempeliopine have been accomplished in 11-12 steps from tryptamines.",10.1021/jacs.1c10279,2021-11-19,0.638871084963373
Synlett,Synthesis of α-Farnesene Hydroperoxides,"All articles of this category A short and efficient synthetic route to two sesquiterpene autoxidation products is presented. The successful strategy involved converting geraniol into conjugated trienyl hydroperoxide ( 3 ). This cyclised efficiently in the presence of oxygen and an initiator to afford the very labile endoperoxy hydroperoxide ( 5 ), a route which mimics α-farnesene autoxidation. hydroperoxide - endoperoxide - synthesis - α-farnesene - autoxidation",10.1055/s-1996-5421,1996-04-01,0.6388539755798067
Organic Letters,Studies toward the Total Synthesis of Caribbean Ciguatoxin C-CTX-1: Synthesis of the LMN-Ring Fragment through Reductive Olefin Cross-Coupling,"Synthesis of the LMN-ring fragment of Caribbean ciguatoxin C-CTX-1, the principal causative toxin for ciguatera fish poisoning around the Caribbean Sea areas, is described. The key feature of the synthesis is the stereoselective introduction of an angular methyl group on the sterically encumbered seven-membered M-ring by the application of a hydrogen atom transfer-based reductive olefin coupling.",10.1021/acs.orglett.8b03102,2018-10-26,0.6388448007206666
Journal of Organic Chemistry,"Assembly of 3a-Arylperhydroindoles by the Intramolecular Cycloaddition of 2-Azaallyl Anions with Alkenes. Total Syntheses of (±)-Crinine, (±)-6-Epicrinine, (−)-Amabiline, and (−)-Augustamine","The 2-azaallyl anion route to pyrrolidines was used for the concise synthesis of alkaloids featuring the 3a-arylperhydroindole nucleus. The brevity and efficiency of the syntheses described are particularly notable. The key transformations involved the tin−lithium exchange of (2-azaallyl)stannanes to 2-azaallyl anions, which participated in intramolecular [π4s + π2s] cycloadditions with styrenes to produce the requisite 3a-arylperhydroindoles. (±)-Crinine was synthesized in eight steps in 20% overall yield, with the key cycloaddition producing a single stereoisomer of the perhydroindole in 80% yield. (±)-6-Epicrinine was an intermediate in this synthesis. The key cycloaddition involved the use of a diene as the anionophile. The first asymmetric syntheses of (−)-amabiline and (−)-augustamine were accomplished in overall yields of 43% (in eight steps) and 42% (in nine steps), respectively, confirming or determining the absolute stereochemistry of the natural products. The key cycloadditions produced the perhydroindoles in 83% and 74% yields, respectively, with reasonable stereocontrol. The highly stereoselective cycloaddition leading to a trans -dialkoxyperhydroindole in 75% yield was consistent with stereochemical predictions. These studies contribute to a growing body of knowledge on the scope and stereochemistry of 2-azaallyl anion cycloadditions.",10.1021/jo972255+,1998-04-30,0.6388302552883015
Journal of Organic Chemistry,Synthesis of Mimosamycin,"Mimosamycin (1) was synthesized in eight steps with an overall yield of 13% from 2-methoxy-3-methyl-1,4-benzoquinone by regioselective introduction of a chloromethyl group at C-6 and a methoxycarbonylmethyl group at C-5 and subsequent reaction of the intermediate methyl (o-(chloromethyl)phenyl)acetate derivative 16 with methylamine. Oxidation of the 5,7,8-trimethoxy-2,6-dimethyl-1, 4-dihydroisoquinoline-3(2H)-one 17 thus obtained, using cerium(IV) ammonium nitrate as a selective oxidizing agent, gave mimosamycin (1) in good overall yield.",10.1021/jo990767d,2000-01-19,0.6388203574351969
Organic Letters,Total Synthesis of (±)-Dragmacidin E,The bis indole sponge alkaloid dragmacidin E was synthesized in racemic form over 25 steps starting from 7-benzhydroxyindole. Key steps include (a) a Witkop cyclization to facilitate construction of the indole-spanning seven-membered ring and (b) a cyclodehydrative pyrazinone synthesis that unites the two indole-containing sectors.,10.1021/ol202535f,2011-09-29,0.6388085473217359
Synthesis,"Regiospecific Synthesis of Benzo[<i>b</i>]fluorenones via Ring Contraction by Benzil-Benzilic Acid Rearrangement of Benz[<i>a</i>]anthracene-5,6-diones","A regiospecific route to benzo[b]fluorenones is described. The synthesis is based upon a one-pot, regiospecific benzannulation of 1,4-dipolar synthons with naphthoquinone monoketal and ring contraction of the generated benz[a]anthracene-5,6-diones through benzil-benzilic acid rearrangement.",10.1055/s-2006-942468,2006-07-25,0.638775925712323
Synthesis,A Convenient New Synthetic Route to Substituted Benz [<i>a</i>]azulenes,,10.1055/s-1971-21688,1971-01-01,0.6387711136851109
Organic Process Research & Development,Development of a Scalable Process for the Insecticidal Candidate Tyclopyrazoflor. Part 2. Fit-for-Purpose Optimization of the Route to Tyclopyrazoflor Featuring [3 + 2] Cyclization of 3-Hydrazinopyridine·2HCl and Methyl Acrylate,"Optimization of the route to the sap-feeding insecticidal candidate tyclopyrazoflor featuring [3 + 2] cyclization of 3-hydrazinopyridine·2HCl and methyl acrylate is described. The key impurities in the [3 + 2] cyclization were identified and successfully controlled after optimization. The hazards associated with oxidation of an intermediate pyrazolidin-3-one using the incompatible combination of potassium persulfate and N, N -dimethylformamide (DMF) were avoided by using potassium ferricyanide in the presence of potassium hydroxide in water. The two elimination impurities in the ethylation step to produce tyclopyrazoflor were successfully minimized using ethyl iodide in the presence of cesium carbonate in DMF at 0 °C. The overall yield for this seven-step synthesis of tyclopyrazoflor was improved from 10% to 41% after the optimization detailed herein.",10.1021/acs.oprd.9b00128,2019-07-01,0.6387661479337328
Tetrahedron,Scalable total synthesis of horsfiequinone A,,10.1016/j.tetlet.2018.02.082,2018-03-05,0.6387637413463201
Tetrahedron,"A New Route to Trans 2,5-Dialkylpyrrolidines",,10.1016/0040-4039(92)88125-o,1992-04-01,0.6387495575186316
Synthesis,"The First Synthesis of 7-Alkylthio-2,2-dimethyl-2<i>H</i>-chromenes, the Sulfur Analogs of Natural and Synthetic Precocenes","All articles of this category A new and expeditious synthesis of 7-alkylthio-2,2-dimethyl-2 H -chromenes in good overall yield (59-72%), utilising the Newman-Kwart rearrangement of 7-( N , N -dimethylthiocarbamoyloxy)-2,2-dimethyl-4-chromanones as the key step, is described",10.1055/s-1994-25585,1994-01-01,0.638742655859554
European Journal of Organic Chemistry,Efficient Synthesis of Multifunctional Chelating Agents Based on Tetraazacycloalkanes,"An efficient route has been developed for the synthesis of multifunctional tetraazacycloalkanes (in particular 1,4,7,10‐tetraazacyclotridecane) incorporating an aminomethyl pendant arm on the carbon skeleton. Starting from the appropriate C‐functionalized bisaminal‐protected intermediate, the target macrocycles were easily obtained by means of a step‐by‐step introduction of the desired functional groups onto the free primary amine group, followed by deprotection of the bisaminal intermediates. This straightforward and versatile synthetic approach paves the way for the design of a new family of multifunctional chelators.",10.1002/ejoc.201800801,2018-08-23,0.6386956239082334
Synthesis,A Facile Synthesis of (+)-L-Discadenine and its Deuterio Derivatives,"All articles of this category The synthesis of discadenine, 3-[(3 S )-3-amino-3-carboxypropyl] -6-(3-methyl-2-butenyl)-3 H -purine, and several of its deuteriated derivatives, which are useful in the study of the stereochemical mechanism of its biosynthesis, have been synthesized in three steps from the appropriate homoserine lactones via a route designed for maximal synthetic versatility. The yields of discadenine obtained from this new route represent a ten-fold increase over previous procedures.",10.1055/s-1988-27529,1988-01-01,0.6386792886319974
Angewandte Chemie International Edition,Total Synthesis of (−)‐Tetrodotoxin and 11‐norTTX‐6(<i>R</i>)‐ol,"The enantioselective total synthesis of (-)-tetrodotoxin [(-)-TTX] and 4,9-anhydrotetrodotoxin, which are selective blockers of voltage-gated sodium channels, was accomplished from the commercially available p-benzoquinone. This synthesis was based on efficient stereocontrol of the six contiguous stereogenic centers on the core cyclohexane ring through Ogasawara's method, [3,3]-sigmatropic rearrangement of an allylic cyanate, and intramolecular 1,3-dipolar cycloaddition of a nitrile oxide. Our synthetic route was applied to the synthesis of the tetrodotoxin congeners 11-norTTX-6(R)-ol and 4,9-anhydro-11-norTTX-6(R)-ol through late-stage modification of the common intermediate. Neutral deprotection at the final step enabled easy purification of tetrodotoxin and 11-norTTX-6(R)-ol without competing dehydration to their 4,9-anhydro forms.",10.1002/anie.201611574,2017-01-11,0.638670255633036
Synthesis,Eight-Step Asymmetric Synthesis of (–)-Berkelic Acid,"Abstract We herein report an eight-step asymmetric synthesis of (–)-berkelic acid. This work features a sequential Catellani-type reaction/oxa-Michael addition with epoxides as dual-functionalized alkylating reagents for synthesizing the isochroman framework, a one-pot, acid-catalyzed deprotection/spiroacetalization process for the construction of a tetracyclic core intermediate, and a late-stage Ni-catalyzed reductive coupling reaction for the installation of the side chain. Remarkably, during the deprotection/spiroacetalization process, four new stereocenters are created with high stereocontrol from a single existing chiral center.",10.1055/a-1799-0459,2022-03-15,0.6386669694938821
Organic Letters,Stereoselective Synthesis of Indolines via Organocatalytic Thioester Enolate Addition Reactions,"A straightforward stereoselective synthesis route to indolin-3-yl acetates has been developed using organocatalytic addition reactions of monothiomalonates to ortho-bromo nitrostyrenes as the key step. The addition products of this highly stereoselective one-pot addition-deprotection-decarboxylation sequence were easily further converted to the target indolin-3-yl acetates, via an intramolecular Buchwald-Hartwig coupling reaction. The route provided indolin-3-yl acetates bearing tertiary and exocyclic quarternary stereogenic centers in excellent stereoselectivities and overall yields of 34-83%.",10.1021/ol501936n,2014-08-07,0.6386561921687177
Tetrahedron,Asymmetric protected enoates as key intermediates towards an EPC synthesis of (+)-heptelidic acid,,10.1016/0040-4039(95)01538-s,1995-10-01,0.6386427979919193
Journal of Organic Chemistry,Total Synthesis and Absolute Stereochemical Assignment of Microgrewiapine A and Its Stereoisomers,"Total synthesis of both enantiomers of (-)-(2 S,3 R,6 S)- and (+)-(2 R,3 S,6 R)-microgrewiapine A along with (+)-microcosamine A and (-)-6- epi-microgrewiapine A from chiral 1-(α-methylbenzyl)-aziridine-2-carboxylate was accomplished for the first time. Key steps involved in this synthesis include one-pot reductive ring-opening of aziridine, debenzylation, intramolecular N-alkylation to obtain the key piperidine ring, and Julia-Kociensky olefination. The absolute configuration of natural microgrewiapine A is assigned as (+)-(2 R,3 S,6 R), which is opposite to the originally proposed structure by comparing optical rotation data of both synthetic enantiomers.",10.1021/acs.joc.8b02342,2018-11-08,0.6386355792158338
Journal of the American Chemical Society,"Asymmetric Divergent Synthesis of <i>ent</i>-Kaurane-, <i>ent</i>-Atisane-, <i>ent</i>-Beyerane-, <i>ent</i>-Trachylobane-, and <i>ent</i>-Gibberellane-type Diterpenoids","A unified strategy toward asymmetric divergent syntheses of nine C8-ethano-bridged diterpenoids A1–A9 (candol A, powerol, sicanadiol, epi -candol A, atisirene, ent -atisan-16α-ol, 4-decarboxy-4-methyl-GA 12, trachinol, and ent -beyerane) has been developed based on late-stage transformations of common synthons having ent -kaurane and ent -trachylobane cores. The expeditious assembly of crucial advanced ent -kaurane- and ent -trachylobane-type building blocks is strategically explored through a regioselective and diastereoselective Fe-mediated hydrogen atom transfer (HAT) 6- exo -trig cyclization of the alkene/enone and 3- exo -trig cyclization of the alkene/ketone, showing the multi-reactivity of densely functionalized polycyclic substrates with π C═C and π C═O systems in HAT-initiated reactions. Following the rapid construction of five major structural skeletons ( ent -kaurane-, ent -atisane-, ent -beyerane-, ent -trachylobane-, and ent -gibberellane-type), nine C8-ethano-bridged diterpenoids A1–A9 could be accessed in the longest linear 8 to 11 steps starting from readily available chiral γ-cyclogeraniol 1 and known chiral γ-substituted cyclohexenone 2, in which enantioselective total syntheses of candol A ( A1, 8 steps), powerol ( A2, 9 steps), sicanadiol ( A3, 10 steps), epi -candol A ( A4, 8 steps), ent -atisan-16α-ol ( A6, 11 steps), and trachinol ( A8, 10 steps) are achieved for the first time.",10.1021/jacs.2c09985,2022-12-20,0.6386269546364473
Organic Letters,Enantioselective Total Synthesis of (+)-Gephyrotoxin 287C,"A synthesis of (+)-gephyrotoxin 287C using (S)-phenylglycinol-derived tricyclic lactam 7 as the starting enantiomeric scaffold is reported. From the stereochemical standpoint, the key steps are the generation of the DHQ C-5 stereocenter by hydrogenation of the C-C double bond, removal of the chiral inductor to give a cis-DHQ, introduction of the DHQ C-2 substituent, completion of the (Z)-enyne moiety, and generation of the C-1 stereocenter during closure of the pyrrolidine ring.",10.1021/acs.orglett.7b03381,2017-11-28,0.6386049933820642
European Journal of Organic Chemistry,A Facile Route to Bulladecin-Type Acetogenins - Total Synthesis of Asimilobinand Correction of the Configuration of Its Tetrahydrofuran Segment,"The most efficient method for the synthesis of the trans/threo/trans-bis(tetrahydrofuran) (THF) ring unit was established, and the first total synthesis of (−)-asimilobin and its diastereomer was then accomplished in twelve and fourteen steps, respectively, from trans-1,5,9-decatriene, by a convergent route with a Wittig reaction as the key step. By virtue of these synthetic results, the absolute configuration of the bis(THF) unit in naturally occurring asimilobin should be corrected.",10.1002/(sici)1099-0690(200001)2000:2<349::aid-ejoc349>3.0.co;2-j,2000-01-01,0.6386005813094748
Journal of Organic Chemistry,A Nine-Step Total Synthesis of (−)-Platencin,"Within 1 year, platencin, a recently discovered antibiotic, has become a highly competitive synthetic target, due to its promising bioactivity and its unusual complex molecular architecture. Herein, a particularly concise total synthesis of platencin starting from inexpensive perillaldehyde is described. The key features of this approach are (1) a highly diastereoselective Diels-Alder reaction with Rawal's dieneforming the first all-carbon quaternary center, (2) a ring-closing metathesis to generate the strained tricylic skeleton, (3) a hydration/dehydration strategy to efficiently shift the endocyclic alkene to the exoposition, and (4) a 1,4-addition of a hindered ketone enolate to methyl acrylate to create the second all-carbon quaternary center. In view of the brevity (nine linear steps) and the overall yield of 10%, our synthesis compares favorably with all the previous ones.",10.1021/jo9001855,2009-03-04,0.6385987759397238
Synthesis,A New Synthesis of 2-(6-Metboxycarbonylhexyl)-cyclopent-2-en-1-one,"All articles of this category A new, simple and short route to 2-(6-methoxycarbonylhexyl)-cyclopent-2-en-1-one(overall yield: 33%) starting from ethyl-10-undecenoate is reported. The main feature of this synthesis is a new cobalt-catalyzed carbonylation of the intermediate epoxide, which occurs with satisfactory yield under very mild conditions.",10.1055/s-1986-31686,1986-01-01,0.638592787924427
Tetrahedron,Improved method for the synthesis of N-methyl-2-oxoalkanesulfonamides.,,10.1016/s0040-4039(00)92534-6,1992-06-01,0.6385787491493995
Organic Letters,Synthesis of 2-Fluoro-11-hydroxy-<i>N</i>-propylnoraporphine:  A Potential Dopamine D<sub>2</sub> Agonist,"[structure: see text]. 2-Fluoro-11-hydroxy-N-propylnoraporphine 4 (2-F-11-OH-NPa) was synthesized from thebaine in 13 steps with an overall yield of 1.35%. The key steps included the Pd-catalyzed 3-dehydroxylation of 14-hydroxymorphine, S(N)2 substitution of Ts(-) by F(-), and CH(3)SO(2)OH-promoted rearrangement of the substituted morphinandiene. The dopamine binding affinity of this compound was also investigated on rat brain membranes, and as expected, this compound displayed high affinity and selectivity at the D(2) receptor.",10.1021/ol051010d,2005-06-18,0.6385625461014186
Synthesis,"Convenient Synthesis of 2-(2,2-Difluoroethoxy)-6-(trifluoromethyl)-benzenesulfonyl Chloride, A Key Building Block of Penoxsulam","A convenient and efficient three-step synthesis of 2-(2,2-difluoroethoxy)-6-(trifluoromethyl)benzenesulfonyl chloride, the key building block of penoxsulam, is described. The main features of the synthesis include a regioselective lithiation and subsequent electrophilic substitution starting from commercially available 3-bromobenzotrifluoride to provide (2-bromo-6-(trifluoromethyl)phenyl)(propyl)sulfane, then a copper-catalyzed C–O coupling to introduce the difluoroethoxy moiety and chloroxidation conditions to give the desired sulfonyl chloride.",10.1055/s-0039-1690617,2019-08-22,0.638560849363754
Organic Process Research & Development,"Development of a Scalable and Safe Procedure for the Production of (3<i>R</i>)-3-(2,3-Dihydro-1-benzofuran-5-yl)-1,2,3,4-tetrahydro-9<i>H</i>-pyrrolo[3,4-<i>b</i>]- quinolin-9-one, an Intermediate in the Synthesis of PDE-V Inhibitors RWJ387273 (R301249) and RWJ444772 (R290629)","A scalable and safe process for the oxidative rearrangement of β-carboline to quinolone derivatives, intermediates in the synthesis of PDE-V inhibitors RWJ387273 (R301249) and RWJ444772 (R290629), has been developed.",10.1021/op060099f,2006-07-12,0.6385545388323233
Journal of Organic Chemistry,Expedient Synthesis of <i>N</i>-Methyl Tubulysin Analogues with High Cytotoxicity,"An optimized and highly efficient synthesis of potent, bioactive N-methyl tubulysin analogues 2 and 4 has been achieved with > 40% overall yields. This synthesis represents a significant improvement over previously reported syntheses of these and related tubulysin analogues. The stereoselective synthesis of the unnatural amino acid tubuvaline is accomplished using tert-butanesulfinamide chemistry. N-Alkylation to form N-methyl tubuvaline is performed without protection of the tubuvaline alcohol by implementing a unique N-methylation strategy via formation and reduction of a 1,3-tetrahydrooxazine heterocycle. Acylation of the hindered N-methyl tubuvaline amine utilizes a novel sequence of O-acylation followed by an O- to N-acyl transfer to form the hindered amide bond between N-methyl tubuvaline and isoleucine. This high-yielding synthesis should enable the production of large quantities of material for biological studies.",10.1021/jo800384x,2008-05-15,0.6385530423066194
Journal of Organic Chemistry,Asymmetric Total Synthesis of the Putative Structure of Diplopyrone,"The first asymmetric total synthesis of the putative structure of diplopyrone was achieved in 17 linear steps starting from cis -1,4-butene-diol. The synthetic route features iodine-catalyzed tandem isomerization followed by C–O and C–C bond formation reaction strategy developed by our own group to construct the trans -2,6-disubstituted dihydropyran ring, asymmetric α-aminoxylation reaction, and Still–Gennari ( Z )-selective olefination reactions. Careful comparison of 1 H and 13 C NMR spectroscopic data as well as investigation of the UV and circular dichroism spectrum in trifluoroethanol for compound 2 suggest that the putative structure for diplopyrone {6-[(1 S )-1-hydroxyethyl]-2,4a( S ),6( R ),8a( S )-tetrahydropyran[3,2- b ]pyran-2-one} requires revision.",10.1021/acs.joc.7b00086,2017-04-07,0.6385455547876062
Synlett,A New Approach to the Synthesis of Aristolactams. Total Synthesis of Cepharanone A and B,"All articles of this category An efficient, concise and tactically new synthesis of aristolactams is described. The key step is the aryne-mediated cyclization of an amino carbanion derived from a phosphorylated halobenzamide derivative. Horner reaction, radical cyclization and ultimate deprotection complete the synthesis of the phenanthrene lactam alkaloids. The viability of the strategy is further illustrated by the synthesis of cepharanone A and B. phosphorylated amino carbanion - aryne-mediated cyclization - Horner-Wittig reaction - radical-mediated cyclization - aristolactams",10.1055/s-1997-1046,2000-12-31,0.6385440216553471
Synlett,Formal Asymmetric Synthesis of a 7-Methoxyaziridinomitosene,"The conversion of (-)-2,3-O-isopropylidene-d-erythronolactone (14) and 2-benzyloxy-6-bromo-4-methoxy-3-methyl­aniline (18) into {(1R,2R)-(-)-1-azido-2,3,5,8-tetrahydro-7-methoxy-6-methyl-2-methanesulfonyloxy-5,8-dioxo-1H-pyrrolo-[1,2-a]indol-9-yl}methyl phenyl carbonate (39) has been accomplished in 17 steps by way of the enaminone 26. Key steps included the preparation of 26 by a Reformatsky reaction on a thiolactam precursor 25, and intramolecular Heck reaction of 26 to form the indole ring. The preparation of 39 constitutes a formal synthesis of the fully functionalised 7-methoxyaziridinomitosene 12, only the second such synthesis to have been accomplished.",10.1055/s-2006-951532,2006-11-23,0.6385415557878658
Organic Letters,"Synthesis of Okaramine M, Its Conversion to Amauromines, and Concise Bidirectional and Biomimetic Total Synthesis of Amauromines","-okaramine M and their conversion into different sets of stereoisomers of amauromines are reported. Moreover, a short bidirectional and biomimetic total synthesis of amauromines is described using an Ir-catalyzed double prenylation as the key step. Accordingly, amauromine with its six stereogenic centers can be prepared in two synthetic steps in enantiomerically pure form starting from unprotected l-tryptophan.",10.1021/acs.orglett.5c02088,2025-06-29,0.6385309169408172
Organic Process Research & Development,Synthesis of Imatinib by C–N Coupling Reaction of Primary Amide and Bromo-Substituted Pyrimidine Amine,"A new method for imatinib synthesis is described by using the C–N coupling reaction of 4-(4-methylpiperazine-1-methyl)benzamide with N -(5-bromo-2-tolyl)-4-(3-pyridyl)pyrimidin-2-amine to form imatinib. In this synthetic route, the high efficiency and high selectivity of nano-ZnO as a catalyst is key to the mild hydrolysis of 4-(4-methylpiperazine-1-methyl)benzonitrile into the corresponding amide. The total imatinib yield was 51.3%, and the purity was 99.9%. This simple and effective synthetic pathway avoids gene-impurity production (as classified by the FDA Center for Drug Evaluation and Research), and the synthesis is environmentally friendly with a short reaction time.",10.1021/acs.oprd.9b00227,2019-07-31,0.6385221416335395
Journal of Organic Chemistry,Conversion of Marcfortine A to Paraherquamide A <i>via </i>Paraherquamide B. The First Formal Synthesis of Paraherquamide A,The paraherquamides and marcfortines represent a novel class of anthelmintics. The sole structural difference between paraherquamide A and marcfortine A occurs in ring G. We synthesized paraherquamide B from marcfortine A in six steps. Paraherquamide A was then prepared from paraherquamide B in seven steps. This represents the first formal synthesis of paraherquamide A.,10.1021/jo9622791,1997-03-01,0.6385192593954598
Angewandte Chemie International Edition,Total Synthesis of (−)‐Himeradine A,"(-)-Himeradine A is a complex lycopodium alkaloid with seven rings and ten stereogenic centers that shows anticancer activity against lymphoma L1210 cells. A total synthesis has been developed that builds off prior work on (+)-fastigiatine. A 2,4,6-trisubstitited piperidine ring forms the core of the quinolizidine segment, and was prepared by diastereoselective reduction of a pyridine and classic resolution of an intermediate. The remaining secondary amine was introduced with a catalyst-controlled Overman rearrangement. The piperidine segment was coupled in a B-alkyl Suzuki reaction with a bicyclic bromoenone, which was a key intermediate for the synthesis of (+)-fastigiatine. The final transformation featured a transannular Mannich reaction and cyclization to complete the quinolizidine. Five bonds and four new rings were generated in this one-pot procedure. (-)-Himeradine A was prepared in 17 steps in the longest linear sequence.",10.1002/anie.201910129,2019-09-06,0.6384934037310206
Tetrahedron,"A new route to the synthesis of imidazo [4,5-c]pyrazoles",,10.1016/s0040-4039(00)82297-2,1988-01-01,0.638454068640758
Organic Letters,Stereocontrolled Formal Synthesis of (±)-Platensimycin,"The caged structure of platensimycin, known as Nicolaou's key intermediate for total synthesis of platensimycin, was synthesized stereoselectively by using the following key steps: (i) diastereoselective Diels-Alder reaction between gamma-benzoyloxy enone and tert-butyldimethylsiloxydiene, (ii) formation of a dihydropyran ring by intramolecular catalytic oxypalladation, and (iii) transannular radical cyclization of monothioacetal with tributyltin hydride and AIBN.",10.1021/ol801584r,2008-08-15,0.6384388432943767
Tetrahedron,"Use of the carbopalladation of 1,2-propadiene in a two step synthesis of steroids",,10.1016/s0040-4039(00)92119-1,1991-02-01,0.6384293609039626
European Journal of Organic Chemistry,From Planning to Optimization: Total Synthesis of Valerenic Acid and Some Bioactive Derivatives,"Abstract A detailed study of the total synthesis of valerenic acid, a well known GABA A receptor subtype modulator, is described. Both successful as well as unsuccessful attempts towards the synthesis of the title compound are presented, including four different strategies to synthesize one of the key intermediates. The first two strategies are based on epoxides provided from the chiral pool, whereas the last two approaches rest on stereocontrolled modifications of 2‐cyclopentenone. The streamlined synthesis implements a new one‐pot reaction, which combines the addition of a Grignard species with an acid‐catalyzed isomerization of the intermediate allylic alcohol. Further highlights are a stereo‐ and regioselective hydroxy‐directed Diels–Alder reaction, a hydroxy‐directed hydrogenation, and a final Negishi coupling reaction. After optimization of our synthesis, the preparation of several easily available derivatives is also discussed. Amides obtained by functionalization of the carboxyl group are more than twice as active as valerenic acid.",10.1002/ejoc.201101834,2012-02-21,0.638409616030039
Journal of the American Chemical Society,Ten-Step Total Synthesis of (±)-Phaeocaulisin A Enabled by Cyclopropanol Ring-Opening Carbonylation,"We report an efficient total synthesis of (±)-phaeocaulisin A, a guaianolide sesquiterpene natural product possessing a complex tetracyclic skeleton embedded with an oxaspirolactone and a fused bicyclic lactone, four oxygen-containing stereocenters, and an 8-oxabicyclo[3.2.1]octane core. Our synthesis features a novel palladium-catalyzed cyclopropanol ring-opening carbonylation to access a key γ-ketoester, a chemo- and stereoselective aldol cyclization to form the seven-membered carbocycle, and a cascade ketalization-lactonization to construct the desired tetracyclic skeleton. With these strategically important C-C and C-O bond formation transformations, a 10-step total synthesis of (±)-phaeocaulisin A was achieved. We further developed the cyclopropanol ring-opening carbonylation chemistry to provide an alternative approach to prepare γ-ketoesters. Biologically, the penultimate intermediate with an α-methylene γ-butyrolactone moiety was identified as a promising lead compound with anticancer proliferation activity against a panel of triple-negative or HER2+ breast cancer cell lines.",10.1021/jacs.4c12121,2024-11-12,0.6384059789863737
Organic Process Research & Development,Preparation of the HIV Attachment Inhibitor BMS-663068. Part 6. Friedel–Crafts Acylation/Hydrolysis and Amidation,"The development of a process for appending the oxalyl amide side chain to the azaindole core of the HIV-attachment inhibitor BMS-663068 is described. A Friedel–Crafts acylation installed the oxalyl ester, which was subsequently hydrolyzed and amidated with a benzoyl piperazine. The development of the commercial route necessitated several key changes to the initial synthesis. For instance, in the original acylation process, nitromethane, a commonly used, but highly energetic cosolvent, was employed which was eventually replaced by catalytic tetra- n -butylammonium bisulfate to overcome gelling issues encountered during the reaction when nitromethane was omitted. It was further demonstrated that the amidation sequence could be relegated to a single-pot, homogeneous transformation through the use of the cost-effective coupling reagent diphenylphosphinic chloride. The above modifications have been utilized in multiple campaigns and reproducibly demonstrated on scales of up to 200 kg input.",10.1021/acs.oprd.7b00133,2017-08-09,0.6383845114682802
Green Chemistry,"Optimization of the use of a chiral bio-based building block for the manufacture of DHPPA, a key intermediate for propionate herbicides","An alternative route for the production of (R)-2-(4-hydroxyphenoxy)propionic acid (DHPPA), a key intermediate in herbicide chemistry, is proposed. This route makes use of a chiral building block, initially produced by fermentation. The route has been optimized based on two steps: chlorination and etherification. The chlorination step has a maximum ee of 99% and a yield of 85% after distillation. The etherification step has a yield of 66%. Comparison of the route with the industrial standard shows a significant improvement in terms of green chemistry: waste streams are lowered up to 7-fold and the toxicity of the waste streams is reduced.",10.1039/c4gc00797b,2014-07-04,0.6383822622991913
Organic Letters,"Concise Synthesis of (<i>S,S</i>)-(+)-Dehydrohomoancepsenolide","A concise total synthesis of the bis-butenolide 3 in optically active form is reported. Key steps are a zinc-mediated ""three-component coupling"" with formation of dienyne 9 which undergoes ring closing metathesis (RCM) on treatment with (PCy(3))(2)Cl(2)Ru=CHPh. Dimerization of the resulting butenolide 11 is then achieved via alkyne metathesis using (tBuO)(3)W&tbd1;CCMe(3) as the catalyst. A Lindlar reduction completes this synthesis which delivers product 3 in only five steps with an overall yield of 25%.",10.1021/ol006122d,2000-07-13,0.638379881067808
Journal of the American Chemical Society,Concise Synthesis of Alkaloid (−)-205B,"Described herein is a short total synthesis of alkaloid (-)-205B (1) by means of an anti-selective SN2' alkylation of an attractively functionalized cyclopropanol and diastereoselective cyclization of the resulting aminoallene adduct for bicyclic ring formation. The synthesis features a general route to cis- or trans-2,6-disubstituted piperidines by lithium aluminum hydride reduction of the imine intermediate by an appropriate choice of solvent and cis- or trans-2,5-disubstituted pyrrolidines by an exceptional level of chirality transfer from a pendant allene. Particularly noteworthy are the brevity and convergence made possible by a segment-coupling strategy.",10.1021/jacs.5b00243,2015-01-30,0.6383774890704684
Journal of Organic Chemistry,Synthesis of (+)-Sulcatine G,"The total synthesis of (+)-sulcatine G is described. A key structural feature of sulcatine G is the highly functionalized, enantiomerically pure cyclobutane ring. We have prepared (+)-sulcatine G using a new strategy for bicyclic ring construction, Rh-mediated intramolecular C-H insertion followed by intramolecular alkylation.",10.1021/jo0508752,2005-07-09,0.6383739028647987
Angewandte Chemie International Edition,"Total Synthesis and Absolute Configuration of Macrocidin A, a Cyclophane Tetramic Acid Natural Product","Stereocontrolled access to the cyclophane framework of macrocidin A has been achieved for the first time. The key steps include the iridium-catalyzed asymmetric hydrogenation without fission of the CI bond, the macrolactam formation by intramolecular ketene trapping, and the Lacey–Dieckmann cyclization for the construction of the tetramic acid ring.",10.1002/anie.200906362,2009-12-28,0.638359783090773
Tetrahedron,Novel and efficient synthesis of 1β-methylcarbapenems utilizing cyclization of hypervalent iodonium ylides,,10.1016/0040-4039(95)01703-k,1995-10-01,0.6383451527625903
Journal of the American Chemical Society,"Application of a Stereospecific Intramolecular Allenylsilane Imino Ene Reaction to Enantioselective Total Synthesis of the 5,11-Methanomorphanthridine Class of <i>Amaryllidaceae</i> Alkaloids","Enantioselective total syntheses of the pentacyclic 5,11-methanomorphanthridine Amaryllidaceae alkaloids (−)-montanine ( 1 ), (−)-coccinine ( 2 ), and (−)-pancracine ( 3 ) were accomplished using an intramolecular concerted pericyclic allenylsilane imino ene cycloaddition as a key step. These complex natural products were constructed starting from readily available enantiomerically pure epoxy alcohol 15 which was converted to allenylsilane aldehyde 28 via an efficient nine-step sequence. The imine generated from aldehyde 28 and iminophosphorane 47 underwent a stereospecific thermal imino ene reaction to afford key intermediate cis aminoalkyne 49 . It was possible to transform this compound via Lindlar hydrogenation followed by an intramolecular Heck reaction to seven-membered ring tetracycle 51 . This olefinic intermediate could be functionalized through its epoxide to yield α-hydroxymethyl intermediate 54, and then pentacyclic alcohol 64 . Procedures were then developed to convert this material to the enantiomerically pure alkaloids 1 − 3 . A formal enantioselective total synthesis of (−)-brunsvigine ( 4 ) was also achieved via triol 72 .",10.1021/ja970839n,1997-06-01,0.6383431209000351
Tetrahedron,Improved formal total synthesis of tetrahydrometinoxocrinine,,10.1016/s0040-4039(00)78735-1,1980-01-01,0.6383424543446996
Tetrahedron,An improved total synthesis of griseofamine A,,10.1016/j.tetlet.2021.152894,2021-02-05,0.6383424543446996
Journal of Organic Chemistry,Chiral Aziridinyl Radicals:  An Application to the Synthesis of the Core Nucleus of FR-900482,An asymmetric route to the core nucleus of the antitumor agent FR-900482 utilizes the cyclization of an aziridinyl radical into a functionalized indole nucleus. The route employs a selective Polonovski reaction and the Hootelé-Dmitrienko rearrangement to install two oxygen atoms.,10.1021/jo961992n,1997-02-01,0.6383421484717355
Journal of Organic Chemistry,Two Scalable Syntheses of (<i>S</i>)-2-Methylazetidine,"Two orthogonal routes for preparing (S)-2-methylazetidine as a bench stable, crystalline (R)-(-)-CSA salt are presented. One route features the in situ generation and cyclization of a 1,3-bis-triflate to form the azetidine ring, while the second route involves chemoselective reduction of N-Boc azetidine-2-carboxylic acid. Both sequences afford the desired product in good overall yields (61% and 49%) and high enantiomeric excess (>99% ee), avoid column chromatography, and are suitable for the large-scale production of this material.",10.1021/acs.joc.6b00149,2016-02-19,0.6383198274803253
European Journal of Organic Chemistry,Concise Synthesis of Norrisolide,"Abstract The marine natural product norrisolide has been synthesized in a convergent manner with a longest linear sequence of 14 steps. The hydrindane portion of the molecules is prepared through conjugate addition of a functionalized allyl group into cyclopentenone, followed by stereoselective trapping of the enolate generated from the resulting enol silyl ether with an allyl electrophile. Ring‐closing metathesis then establishes the 6–5 ring system. Likewise, selective preparation of the side chain features an enantioselective cyclopropanation of furan‐2‐one, followed by rearrangement and hydrogenation. Coupling of the two major fragments through a Shapiro reaction, followed by reduction and olefination then completes the carbon framework of the natural product. The final steps of the synthesis involve adjustments to the oxidation state of the side chain. New strategies to generate both the hydrindane core and the oxidized side chain has allowed for the more concise and efficient preparation of the natural product.",10.1002/ejoc.201200134,2012-03-13,0.6382900404804501
Tetrahedron,"Synthesis of highly substituted 2,6-anti-configured tetrahydropyrans. First steps towards an efficient access to amphidinol 3 ring system",,10.1016/j.tetlet.2005.04.041,2005-04-28,0.6382880190225867
Tetrahedron,"The convergent synthesis of CI-981, an optically active, highly potent, tissue selective inhibitor of HMG-CoA reductase",,10.1016/s0040-4039(00)74190-6,1992-04-01,0.6382803825047167
Angewandte Chemie International Edition,First Stereoselective Total Synthesis of a Dimeric Naphthoquinonopyrano‐γ‐lactone: (+)‐γ‐Actinorhodin,"We have accomplished the first total synthesis of an isomerically pure naphthoquinonopyrano-γ-lactone dimer, γ-actinorhodin, in eleven steps. Two steps exploit pairs of peri-MeO groups as unusual selectivity controls. The respective MeO groups convey the steric bulk of a bromo or iodo substituent located ortho to one MeO group as steric hindrance into the vicinity of the second MeO group. This relay effect was indispensable for exerting regiocontrol in an aromatic bromination and diastereocontrol in an oxa-Pictet-Spengler cyclization. The absolute configuration of our target compound was established in an asymmetric Sharpless dihydroxylation of a β,γ-unsaturated ester, which was synthesized in a Heck coupling of a bromoiodonaphthalene with ethyl vinylacetate. The dihydroxylation provided the γ-hydroxylactone moiety of the bromonaphthalene that was used as the substrate in the oxa-Pictet-Spengler cyclization. Dimerization to the core of γ-actinorhodin occurred by two Suzuki couplings.",10.1002/anie.201611183,2017-02-17,0.6382393894884927
Journal of Organic Chemistry,De Novo Asymmetric Synthesis of 8a-<i>epi</i>-Swainsonine,"An enantioselective and diastereocontrolled approach to 8a-epi-d-swainsonine has been developed from achiral furfural. The key step to this synthesis was a one-pot procedure for the hydrogenolytic removal of two protecting groups and two intramolecular reductive amination reactions. The absolute stereochemistry was introduced by asymmetric Noyori reduction of furfuryl ketone. This route relies on diastereoselective palladium-catalyzed glycosylation to install the anomeric bond, and Luche reduction, diastereoselective dihydroxylation to set up the manno-stereochemistry of the indolizidine precursor.",10.1021/jo702476q,2008-02-01,0.6382365286071893
Organic Letters,Enantioselective Total Synthesis of (−)-Laurenditerpenol,"A highly convergent total synthesis of (-)-laurenditerpenol has been accomplished through an organolithium to aldehyde nucleophilic addition. Preparation of the prerequisite key intermediates in optically pure form was based on an improved, short, and efficient synthesis of ""wine lactone"" from (S)-limonene and Corey's catalytic enantioselective Diels-Alder reaction of 2,5-dimethyl furan with diethyl fumarate.",10.1021/ol302106y,2012-08-20,0.6382303308615449
Organic Process Research & Development,The Combination of Hydroformylation and Biocatalysis for the Large-Scale Synthesis of (<i>S</i>)-Allysine Ethylene Acetal,"The compound, ( S )-2-amino-5-[1,3]dioxolan-2-yl-pentanoic acid [( S )-allysine ethylene acetal], is a key intermediate in a number of angiotension-I converting enzyme (ACE) and neutral endopeptidase (NEP) inhibitors currently in clinical trials. Through a combination of our hydroformylation and biocatalysis technologies we have developed an efficient five-step synthetic route to this material starting from crotonaldehyde. The development of this process, leading to a large-scale commercial manufacturing campaign, is described in this paper.",10.1021/op100258j,2010-11-17,0.6382242100525061
Organic Letters,Synthetic Studies on Cyathins:  Enantioselective Total Synthesis of (+)-Allocyathin B<sub>2</sub>,"[reaction: see text] The enantioselective total synthesis of (+)-allocyathin B(2) has been achieved. Our approach features a convergent enantioselective construction of the 5-6-7 tricyclic core system using the originally developed chiral building blocks via asymmetric catalysis, the intramolecular aldol reaction in high yield, successful samarium diiodide-mediated ring expansion, and a newly developed double-bond installation method.",10.1021/ol048010i,2004-11-26,0.6382133069603216
Journal of Organic Chemistry,De Novo Approach to 2-Deoxy-β-glycosides:  Asymmetric Syntheses of Digoxose and Digitoxin<sup>1</sup>,"A highly enantioselective and straightforward route to trisaccharide natural products digoxose and digitoxin has been developed. Key to this approach is the iterative application of the palladium-catalyzed glycosylation reaction, reductive 1,3-transposition, diastereoselective dihydroxylation, and regioselective protection. The first total synthesis of natural product digoxose was accomplished in 19 total steps from achiral 2-acylfuran, and digitoxin was fashioned in 15 steps starting from digitoxigenin 2 and pyranone 8beta. This flexible synthetic strategy also allows for the preparation of mono- and disaccharide analogues of digoxose and digitoxin.",10.1021/jo062534+,2007-03-01,0.6382095306674167
Journal of Organic Chemistry,Convergent Synthesis of the Dihydropyran Core Containing the C1–C15 Subunit of Sorangicin A Employing Gold(I)-Catalyzed Cyclization of an Allenic Alcohol,"A convergent route to the C1-C15 subunit of sorangicin A is disclosed. The key steps include carbon-carbon bond formation using an α-chloro sulfide, regioselective hydrozirconation of an internal alkyne for the preparation of a trisubstituted iodoalkene, allene formation using the Myers-Movassaghi protocol, stereoselective reduction of allylic and propargylic ketones using Noyori's catalyst, and gold(I)-catalyzed cyclization of a β-hydroxy allene to construct the dihydropyran ring.",10.1021/acs.joc.6b01743,2016-10-10,0.6381843702763843
Synlett,Catalytic Enantioselective Synthesis of the Phosphodiesterase Type IV Inhibitor (<i>R</i>)-(-)-Rolipram <i>via</i> Intramolecular C-H Insertion Process,"All articles of this category A new route to the phosphodiesterase type IV inhibitor ( R )-(-)-rolipram ( 1 ) has been developed, wherein the key step relies on enantioselective intramolecular C-H insertion of N -alkyl- N -4-nitrophenyl-α-methoxycarbonyl-α-diazoacetamide 7 catalyzed by chiral dirhodium(II) complex. The dirhodium(II) carboxylate, Rh 2 ( S -BPTTL) 4 , incorporating N -benzene-fused-phthaloyl-( S )- tert -leucinate as a bridging ligand has proven to be the catalyst of choice for this process, providing the desired 2-pyrrolidinone 8 in 88% ee. ( R )-(-)-rolipram - phosphodiesterase inhibitor - enantioselective synthesis - chiral dirhodium(II) catalyst - C-H insertion",10.1055/s-1999-2958,1999-11-01,0.6381794843064749
Organic Letters,Total Synthesis of (+)-Muricatetrocin B via a Late-Stage Co-Catalyzed Hartung–Mukaiyama Cyclization,"Convergent total synthesis of (+)-muricatetrocin B, a tetrahydrofuran-containing acetogenin with potent and selective cytotoxicity against the HT-29 human colon adenocarcinoma cell line, was achieved in 13 steps. Our synthesis is highlighted by a late-stage sequential olefin cross-metathesis/Hartung–Mukaiyama cyclization for convergent assembly of the 2,5- trans -substituted tetrahydrofuran ring.",10.1021/acs.orglett.3c01932,2023-08-02,0.6381774218008238
Journal of the American Chemical Society,Enantioselective Total Synthesis of (+)-Amphidinolide T1,"An enantioselective first total syntheis of amphidinolide T1 (1) is described. Amphidinolide T1 (1), a 19-membered macrolide isolated from Amphidinium sp., has shown potent antitumor properties against a variety of NCI tumor cell lines. The synthesis is convergent and involves the assembly of C1-C10 segment 2 and C11-C21 segment 3 by an oxocarbenium ion-mediated alkylation and Yamaguchi macrolactonization sequence. The synthesis of fragment 2 involves an efficient cross metathesis and hydrogenation sequence between the terminal olefins of 5 and 6 to form the C4-C5 carbon-carbon bond. Enol ether 4 is designed to be the surrogate of fragment 3 where the sensitive C16-exo-methylene and the C13-hydroxyl group were protected as the bromoether derivative during the Lewis acid-catalyzed alkylation process. Both stereocenters in fragment 5 as well as the C2 and C3 stereocenters in fragment 4 are accessed by a highly diastereoselective ester-derived titanium enolate-mediated syn-aldol reaction. The bromoether derivative 24 was unraveled at the final stage of the synthesis, providing (+)-amphidinolide T1.",10.1021/ja021385j,2003-02-06,0.638176829423502
Synlett,Total Synthesis of Marine Macrolide Natural Products by the Macrocyclization/Transannular Pyran Cyclization Strategy,"Abstract In this Account, we summarize the development of a new strategy for streamlined synthesis of tetrahydropyran-embedded macrolactones and its successful implementation to a 13-step synthesis of (–)-exiguolide and an 11-step synthesis of (+)-neopeltolide. 1 Introduction 2 Development of Macrocyclization/Transannular Pyran Cyclization Strategy 3 Total Synthesis of (–)-Exiguolide 4 Total Synthesis of (+)-Neopeltolide 5 Conclusions",10.1055/a-2181-9876,2023-09-26,0.6381647352478542
Tetrahedron,Binding of caffeine by a synthetic co-receptor,,10.1016/s0040-4039(00)00506-2,2000-05-01,0.6381603659904154
Journal of Organic Chemistry,"Synthesis of Enantiopure 4-Hydroxypipecolate and 4-Hydroxylysine Derivatives from a Common 4,6-Dioxopiperidinecarboxylate Precursor","tert-Butyl 2-substituted 4,6-dioxo-1-piperidinecarboxylates 4 have been prepared in good yield starting from Boc-Asp-O(t)Bu and other beta-amino acids. By analogy with chiral tetramic acids, their reduction by NaBH(4) in CH(2)Cl(2)/AcOH afforded the corresponding cis-4-hydroxy delta-lactams in good yield and stereoselectivity (68-98% de). In the absence of the A(1,3) strain (reduction of 6-substituted 2,4-dioxo-1-piperidines 7), the cis-4-hydroxy isomer was still obtained as the major product but the de values were consistently lower. 4-Hydroxy-6-oxo-1,2-piperidinedicarboxylate 2a, readily accessible from Boc-Asp-O(t)Bu (three steps, 63% overall yield), has proven to be an excellent building block for the synthesis of cis- and trans-4-hydroxypipecolates 17 and 24 (52 and 36% overall yield, respectively) and for the synthesis of a protected 4-hydroxylysine derivative 29 (41% overall yield).",10.1021/jo0353886,2003-12-10,0.6381583160512764
Synlett,New Synthesis of (Z)- and (E)-3-Styryl-4-quinolones,A novel and efficient route for the synthesis of (Z)- and (E)-3-styryl-4-quinolones is described. Wittig reaction of 4-(chloroquinoline- and quinolone)-3-carbaldehydes with benzylic ylides is the key transformation for this synthetic route. The (Z)-1-methyl-3-styryl-4-quinolone is obtained with high diastereoselectivity from the reaction of 1-methyl-4-quinolone-3-carbaldehyde; while (E)-3-styryl-4-quinolone is prepared through the Wittig reaction of 4-chloroquinoline-3-carbaldehyde followed by acid hydrolysis. Both synthetic routes are efficient regardless of the substituents on the benzylic ylides.,10.1055/s-0030-1258042,2010-08-12,0.6381446104678214
Tetrahedron,A new and versatile route for the synthesis of highly substituted benzenoids,,10.1016/s0040-4039(00)97412-4,1990-01-01,0.6381357230609882
Synthesis,"Synthesis of Tetrahydropyrazolo[1,5-c]pyrimidine-2,7(1H,3H)-diones","A series of tetrahydropyrazolo[1,5- c ]pyrimidine-2,7(1 H ,3 H )-diones 3a – h as the first representatives of the so far unexplored saturated heterocyclic system have been synthesized, formally in 12 steps from methyl acrylate ( 4 ). The synthesis comprises a four-step preparation of methyl N -Cbz-5-alkylamino-3-oxopentanoates 9a–c , their three-step transformation into 5-{2-[(alkyl)(benzyloxycarbonyl)amino]ethyl}pyrazolidin-3-ones 12a – c , three-step selective alkylation of the amidic N-2 to give 2-alkyl-5-{2-[(alkyl)(benzyloxycarbonyl)amino]ethyl}pyrazolidin-3-ones 16b – h , followed by hydrogenolytic Cbz-deprotection and subsequent cyclization of the intermediate 1,4-diamine with CDI to furnish the title compounds 3 . Most of the synthetic steps were performed as a one-pot transformation.",10.1055/s-0032-1318107,2013-01-24,0.638111657048519
Synlett,First Total Synthesis of Jomthonic Acid A,"A stereoselective total synthesis of jomthonic acid A is described. The key features of the synthetic strategy are a Sharpless asymmetric epoxidation, a Gilmann reagent-induced methylation, a Mitsunobu reaction, a Yamaguchi esterification, and an O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (TBTU)-mediated amide coupling. Jomthonic acid A is an architecturally rare amino acid containing a β-methylphenylalanine residue and a 4-methyl-(2E,4E)-hexa-2,4-dienoate moiety. It shows antidiabetic and antiatherogenic activities when tested against mouse ST-13 preadiopocytes.",10.1055/s-0039-1691503,2019-11-29,0.6381084885652005
Organic Letters,Enantioselective Synthesis of (−)-Basiliskamide A,"Basiliskamide A is an antifungal polyketide natural product isolated by Andersen and co-workers from a Bacillus laterosporus isolate, PNG-276. A nine-step enantioselective synthesis of (-)-basiliskamide A is reported, starting from commercially available β-hydroxy ester 7. The synthesis features a highly diastereoselective mismatched double asymmetric δ-stannylallylboration reaction of aldehyde 5 with the bifunctional allylborane reagent 4.",10.1021/ol300282e,2012-02-28,0.6381063390376934
Synlett,Highly Efficient Synthesis of Digoxin,"Abstract Taking advantage of the reliable stereocontrol capability of DMNPA group via long-distance-participation (LDP) effect as well as the mild and efficient deprotection conditions, the first and highly efficient synthesis of digoxin was achieved through a nine-step longest linear sequence with 41% overall yield.",10.1055/a-1346-5650,2021-01-05,0.6380931055110379
European Journal of Organic Chemistry,Synthetic Studies of Kinamycin Antibiotics: Stereoselective Synthesis of the Highly Oxygenated D‐Ring and Construction of the ABD‐Ring System of Kinamycins,"Abstract A concise and stereoselective synthesis of the highly oxygenated D‐ring of the kinamycin family of antitumor antibiotics was achieved from commercially available 3‐methyl‐2‐cyclohexen‐1‐one. The key steps included a regioselective isomerization of a cis ‐epoxy alcohol, a regioselective reductive ring opening of a benzylidene ketal, and a stereoselective α‐hydroxy‐directed ketone reduction. The Ullmann coupling between a bromonaphthaldehyde AB‐ring fragment and an α‐iodocyclohexenone, which is a versatile D‐ring precursor, effected the construction of the functionalized ABD‐ring system that may provide access to kinamycin F and its structural analogues.",10.1002/ejoc.201300858,2013-08-06,0.6380731879751078
Angewandte Chemie International Edition,Collective Asymmetric Total Synthesis of C‐11 Oxygenated <i>Cephalotaxus</i> Alkaloids,"While numerous studies pertaining to the total synthesis of Cephalotaxus alkaloids have been reported, only two strategies have been reported to date for the successful synthesis of the C-11 oxygenated subset, due to the additional synthetic challenge posed by the remote C-11 stereocenter. Herein, we report the collective asymmetric total synthesis of C-11 oxygenated Cephalotaxus alkaloids using a chiral proline both as a starting material and as the only chirality source. A tetracyclic advanced intermediate was synthesized in a highly stereoselective manner from l-proline in 8 steps involving sequential chirality transfer steps such as a diastereoselective N-alkylation, stereospecific Stevens rearrangement and intramolecular Friedel-Crafts reaction via an unusual O-acyloxocarbenium intermediate. From a common intermediate, the asymmetric total synthesis of six C-11 oxygenated Cephalotaxus alkaloids was completed by a series of oxidation state adjustments.",10.1002/anie.202101766,2021-03-18,0.6380553978469015
Tetrahedron,"Lipase-catalyzed transesterification as a practical route to homochiral acyclic anti-1,2-diols. A new synthesis of (+)- and (−)-endo-brevicomin",,10.1016/0040-4039(95)01237-c,1995-08-01,0.6380417003774532
Organic Letters,Expedited Total Synthesis of (±)-Brevianamide A via the Strategic Use of Gold(I) Catalysis,"Two concise and complementary routes to the polycyclic alkaloid (±)-brevianamide A from readily available amino acid building blocks are presented. Key to the synthesis is the strategic use of a gold(I)-catalyzed cascade process that quickly assembles the characteristic pseudoindoxyl motif of the natural product along with the two adjacent quaternary centers in a single step. This sequence, which exemplifies the structural complexity that can be achieved with gold catalysis, allowed for the shortest and highest-yield synthesis of (±)-brevianamide A to date (four steps LLS, 14% overall yield).",10.1021/acs.orglett.2c02971,2022-09-28,0.6380316781313401
European Journal of Organic Chemistry,A Protecting‐Group‐Free Route to Chiral BINOL–Phosphoric Acids,"Abstract A two‐step, protecting group‐free route for the synthesis of 3,3′‐disubstituted and 6,6′‐disubstituted chiral BINOL–phosphoric acids has been realized starting from commercially available brominated BINOLs. This synthesis relies on the direct Suzuki coupling of brominated BINOL phosphoric acids. This synthetic strategy is more efficient compared to previous circuitous strategies involving protections and deprotections, and the process is higher yielding relative to the alternative two‐step synthesis involving Suzuki coupling of the BINOL.",10.1002/ejoc.201100328,2011-05-20,0.6380279555744275
Tetrahedron,"A three-step and enantioselective synthesis of (−)-(S)- or (+)-(R)-2-(furan-3-yl)-3,6-dihydro-2H-pyrans",,10.1016/s0040-4039(99)02337-0,2000-03-01,0.6380239475643459
European Journal of Organic Chemistry,First Stereoselective Total Synthesis and Biological Evaluation of Amphidinin B and Its Analogues,"Abstract A highly stereoselective first total synthesis of amphidinin B is described. The key steps involved in this synthesis are the generation of the exo ‐double bond in the C 1 –C 9 segment, the Barbier allylation, enzymatic kinetic resolution, and the construction of the C 10 –C 21 segment by Sharpless asymmetric epoxidation, base‐induced epoxide ring‐opening, radical cyclization, diastereoselective reduction of the exo ‐cyclic double bond, one‐pot allylation followed by debenzylation, Evans alkylation, and Yamaguchi esterification.",10.1002/ejoc.201001205,2010-12-14,0.638018311586367
Organic Letters,"Toward a Unified Approach for the Lycopodines: Synthesis of 10-Hydroxylycopodine, Deacetylpaniculine, and Paniculine","The enantioselective syntheses of 10-hydroxylycopodine, deacetylpaniculine, and paniculine have been accomplished through use of a common intermediate. Key steps in the synthetic sequence toward these lycopodium alkaloids include formation of the tricyclic core via a conformationally accelerated, intramolecular Mannich cyclization and an organocatalyzed, intramolecular Michael addition to form the C(7)-C(12) linkage.",10.1021/ol303272w,2013-02-05,0.6380045509346953
Organic Letters,"Stereoselective Synthesis of <i>cis</i>-1,3-Disubstituted Cyclobutyl Kinase Inhibitors","Two synthetic routes to a series of structurally novel kinase inhibitors containing a cis-1,3-disubstituted cyclobutane are described. The first route utilized addition of 3-aminocyclobutanol to 1,4-dinitroimidazole 5 as the crucial step in preparing 1, whereas the second route employed a novel 1,4-addition of 4-nitroimidazole 18 to in situ generated cyclobutenone 17 as the key reaction. This allowed for a stereoselective and shorter synthesis that eliminated the use of potentially explosive 1,4-dinitroimidazole 5. [structure: see text]",10.1021/ol049416y,2004-05-01,0.6380017377322279
Synthesis,Studies towards the Synthesis of (–)-Pulvomycin: Construction of the C12–C40 Segment by a Stereoselective Aldol Reaction,Abstract A convergent strategy was developed for the synthesis of the C12–C40 segment of (–)-pulvomycin. Key step was a diastereoselective aldol reaction between a chiral ethyl ketone representing the C24–C40 fragment and a chiral aldehyde representing the C12–C23 fragment. Both compounds were prepared from enantiomerically pure building blocks in a convergent fashion. The longest linear sequence commenced with a known d-fucose-derived glycosyl donor and entailed a total number of 16 steps. The desired anti-aldol product was obtained in a total yield of 5% over these steps and contains 12 out of 13 stereogenic centers present in the natural product.,10.1055/a-1464-2576,2021-03-25,0.6379967050474032
Synthesis,"Scalable Synthesis of Hydrido-Disiloxanes from Silanes: A One-Pot Preparation of 1,3-Diphenyldisiloxane from Phenylsilane","A simple, one-pot, and high-yielding synthesis of 1,3-diphenyldisiloxane is presented. The preparation of similar symmetrical disiloxane materials is also accomplished with this same protocol. This mechano-chemical procedure is efficient and highly scalable, furnishing a convenient route to hydrido-disiloxanes from widely accessible commercially available silanes.",10.1055/s-0036-1588580,2017-09-26,0.6379830387093168
Organic Process Research & Development,Structural Similarity and Its Surprises:  Endothelin Receptor Antagonists - Process Research and Development Report,"Process research and pilot plant processes are described for three endothelin (ET) receptor antagonists. The efficient synthesis of the parent compound Darusentan proceeds via a Darzens reaction from chloroacetate with benzophenone, addition of methanol to the resulting epoxide, saponification of the alkyl propionate and optical resolution of the racemic acid by crystallisation with a chiral amine. The final stage of the synthetic sequence involves the introduction of a pyrimidine moiety. Intermediates formed during this process can be used as starting materials for the synthesis of the two other ET receptor antagonists BSF 420627 and BSF 302146. An ether exchange reaction, which replaces the methoxy with a phenethyloxy substituent, enabled BSF 420627 to be prepared. The synthetic route to BSF 302146 employs trimethylaluminum to methylate the epoxide produced by the Darzens reaction.",10.1021/op000040n,2000-11-05,0.6379748216330935
Synlett,"An Enantioselective Synthesis of the Antifungal Agent (2R, 3R)-2-(2,4-Difluorophenyl)-3-(methylsulfonyl)-1-(1,2,4-triazol-1-yl)-2-butanol (Sch 42427; SM 9164)",All articles of this category A synthesis of Sch 42427 (SM 9164) 1 1 is described utilising a novel two step olefin inversion process and a Sharpless asymmetric epoxidation (AE) reaction as the key steps. antifungal - Sharpless epoxidation - olefin inversion,10.1055/s-1995-5217,1995-11-01,0.637973676228219
Journal of Organic Chemistry,Synthesis of Hexahelicene and 1-Methoxyhexahelicene via Cycloisomerization of Biphenylyl-Naphthalene Derivatives,"The new approach provides nonphotochemical syntheses of helicenes based on the easy, convergent, and modular assembly of key biphenylyl-naphthalenes and their platinum-catalyzed double cycloisomerization. This sequence of reactions provides a synthetic route to helicenes in two steps from simply accessible building blocks. Furthermore, the method enables the introduction of substituents into the hexahelicene skeleton. The strategy developed is exemplified by the synthesis of 6,10-dimethylhexahelicene and 1-methoxy-6,10-dimethylhexahelicene.",10.1021/jo900077j,2009-03-16,0.6379447795295048
Journal of Organic Chemistry,Toward an Asymmetric Synthesis of the Dimeric Pyranonaphthoquinone Antibiotic Crisamicin A,"A full account of our efforts toward an asymmetric synthesis of crisamicin A are presented. The key steps include a Hauser-Kraus annulation of a cyanophthalide with a chiral enone-lactone, a stereoselective cyclization-reduction to install the pyran unit, and a Suzuki homocoupling to forge the key biaryl bond. This work has culminated in the asymmetric synthesis of a dimer bearing the complete carbon skeleton of the dimeric pyranonaphthoquinone natural product crisamicin A.",10.1021/jo501344c,2014-07-16,0.6379409684964522
Organic Letters,A Formal Synthesis of (-)-Cephalotaxine,"An enantioselective formal synthesis of the alkaloid (-)-cephalotaxine has been completed, using an alkylidene carbene 1,5-CH insertion reaction as a key step to construct the spiro[4.4]azanonane core D/E-ring system. A Heck-type cyclization was used to close the tetrahydroazepine C-ring and a selective epoxidation-rearrangement sequence was used to elaborate the E-ring.",10.1021/ol8010166,2008-06-13,0.6379195297177374
Journal of Organic Chemistry,Total Synthesis of (+)-Dihydrocuscohygrine and Cuscohygrine,"The first enantioselective synthesis of (+)-dihydrocuscohygrine 1 and cuscohygrine 2 is presented. 1 was obtained in nine steps and 30% overall yield with a ruthenium-catalyzed tandem ring rearrangement metathesis key step starting from enantiomerically pure cycloheptene-1,3,5-triol derivative 6. The unknown absolute configuration of natural dihydrocuscohygrine 1 could be determined as (S,S)-(-). Cuscohygrine 2 was obtained by Jones oxidation of 1 in quantitative yield but unfortunately with complete epimerization.",10.1021/jo025666l,2002-08-06,0.6379189522708679
Tetrahedron,Total synthesis of sanjoinine A (frangufoline),Sanjoinine A (1) was synthesized from a 14-membered cyclopeptide prepared from a Garner aldehyde derived from d-serine. The key steps in the synthesis were the catalytic asymmetric reduction of ketone 2(b) and the final removal of the Boc group.,10.1016/s0040-4039(98)02278-3,1998-12-01,0.6379129920125187
Journal of the American Chemical Society,Bioinspired Total Syntheses of Skeletally Diverse <i>Lycopodium</i> Alkaloids,"The phlegmarine skeleton is widely recognized as a key biogenetic intermediate in Lycopodium alkaloids. On this basis, we designed a phlegmarine-derived common intermediate that enables the collective, asymmetric total syntheses of 12 Lycopodium alkaloids with five distinct carbon skeletons. This intermediate was prepared on a decagram scale using commercially available ( R )-pulegone in an eight-step sequence, with a stereoselective Michael addition as a key transformation. Subsequent selective carbon–carbon bond formation of this pivotal intermediate─(C4–C10, C4–C12, C1–C14, and C4–C13)─along with a skeletal rearrangement, delivered five frameworks: the huperzimine, lycodine, lycopodine, and phlegmarine classes, which were represented by (−)-hupserrine A, (−)-β-obscurine, (−)-lycopodine, (−)-cermizine B, and the lyconadin C diastereomer, respectively. Furthermore, we developed the first asymmetric total synthesis of (−)-hupserrine A, which bears a complex [6/6/5/6/7] pentacyclic cage structure and inhibits the 5-HT3A receptor (IC 50 = 10.6 μM).",10.1021/jacs.5c15169,2025-10-23,0.6378978312634589
Organic Letters,"Total Synthesis of the 2,5-Disubstituted γ-Pyrone E1 UAE Inhibitor Himeic Acid A","The first total synthesis of the E1 ubiquitin-activating enzyme inhibitor, himeic acid A, is reported. A McCombie reaction was used to form the core γ-pyrone via a 6π-electrocyclization. A dioxenone ring-opening/acyl ketene trapping reaction with a primary amide provided the unusual unsymmetrical imide functionality. Other key steps include the use of an Evans auxiliary alkylation (d.r. ≥ 95:5) to install the ( S )-2-methyl succinic acid fragment and a cross-metathesis to install the unsaturated side-chain.",10.1021/acs.orglett.3c02761,2023-10-06,0.6378957318730787
Synthesis,"A Microwave-Assisted Alternative Synthesis of 8-Amino-2-methyl-3,4-dihydroisoquinolin-1-one","A shorter, alternative synthesis of 8-amino-2-methyl-3,4-dihydroisoquinolin-1-one is described in 32% overall yield, over three steps starting from commercially available 2-methyl-6-nitrobenzonitrile. The synthesis includes two ‘one-pot’ procedures in which the key process involves the microwave-assisted hydrolysis of a nitrile group followed by lactamization under elevated temperatures.",10.1055/s-2007-965978,2007-03-27,0.6378915902796376
Journal of Organic Chemistry,The Synthesis of Deoxyfusapyrone. 2. Preparation of the Bis-Trisubstituted Olefin Fragment and Its Attachment to the Pyrone Moiety,A convergent and modular synthesis has been devised to construct the eight diastereoisomers of deoxyfusapyrone (1). In this paper the synthesis of the complex polyene chain is reported as is its connection to the pyrone moiety that is in the middle of the structure of the final target molecule. This route has been fully worked out for one of the isomers and will now be applied in a parallel synthesis format to make all the stereoisomers of 1.,10.1021/jo034371k,2003-06-06,0.6378876829118447
Organic Letters,Asymmetric Total Syntheses of Megacerotonic Acid and Shimobashiric Acid A,"The asymmetric total syntheses of the α-benzylidene-γ-butyrolactone natural products megacerotonic acid and shimobashiric acid A have been accomplished in nine and 11 steps, respectively, from simple, commercially available starting materials. The key step for each synthesis is the (arene)RuCl(monosulfonamide)-catalyzed dynamic kinetic resolution-asymmetric transfer hydrogenation (DKR-ATH) of racemic α,δ-diketo-β-aryl esters to establish the absolute stereochemistry. Intramolecular diastereoselective Dieckmann cyclization forms the lactone core, and ketone reduction/alcohol elimination installs the α-arylidene.",10.1021/acs.orglett.5b00140,2015-02-20,0.6378869124024094
Synlett,Synthesis of 2-Aryl-Substituted Chromans by Intramolecular C-O Bond Formation,A synthetic route for the preparation of 2-aryl-substituted chromans from commercially available starting materials and utilizing either a palladium- or copper-catalyzed intramolecular cyclization of aryl bromides is described. Chromans with stereocontrol at C-2 can thus be obtained via a palladium-catalyzed asymmetric allylic etherification procedure utilizing a chiral indole-phosphine oxazoline (IndPHOX) ligand.,10.1055/s-0031-1290607,2012-03-15,0.6378751684150145
Journal of Organic Chemistry,"Synthesis of (<i>S</i>,<i>S</i>)-Isodityrosine by Dötz Benzannulation","[reaction: see text] A synthesis of (S,S)-isodityrosine 1, a naturally occurring, key structural subunit of numerous biologically active macromolecules, is described. A formal [3 + 2 + 1] cycloaddition (Dötz benzannulation) approach was utilized to simultaneously construct an aromatic ring and the diaryl ether linkage in one step. This key step was extended to the synthesis of (S,S)-isodityrosine in two separate convergent synthetic routes. This method demonstrates a novel and mild method for the synthesis of diaryl ethers.",10.1021/jo050363n,2005-08-05,0.6378751602545857
Tetrahedron,"An efficient synthesis of cobactin T, a key component of the mycobactin class of siderophores","Nα-Cbz-L-lysine t-butyl ester was oxidized by dimethyldioxirane to give nitrone 8c, which was converted to azopine derivative 15. Subsequent coupling and deprotection reactions afforded an efficient synthesis of cobactin T (19).",10.1016/0040-4039(95)01318-c,1995-09-01,0.6378741453121758
Organic Letters,A Diastereoselective Formal Synthesis of Berkelic Acid,"A formal synthesis of berkelic acid is reported. The strategy employs the combination of a chiral exocyclic enol ether and an achiral isochromanone to afford the chroman spiroketal core via a base-triggered generation and cycloaddition of an o-quinone methide intermediate. Other key steps include equilibration of the spiroketal, intramolecular benzylic oxidation, and lactone addition/hemiketal reduction; all occur with good diastereoselectivity.",10.1021/ol102652t,2010-12-07,0.6378635857726205
Tetrahedron,"Addition of elemental selenium to phosphonate carbanions- - a key step in the synthesis of vinylphosphonates. A new synthetic approach to 1,4-dicarbonyl systems.",,10.1016/s0040-4039(01)81837-2,1981-01-01,0.637859505892658
Synthesis,Short Enantioselective Formal Synthesis of (–)-Platencin,"A short enantioselective formal synthesis of the antibiotic natural product platencin is reported. Key steps in the synthesis include enantioselective decarboxylation alkylation, aldehyde/olefin radical cyclization, and regioselective aldol cyclization.",10.1055/s-0037-1610437,2018-07-23,0.6378583072505173
Synthesis,"A Convenient Asymmetric Synthesis of the Unnatural Amino Acid 2,6-Dimethyl-L-tyrosine","All articles of this category The title compound was prepared in high optical purity by a five-step synthesis from 3,5-dimethylphenol on a kilogram scale. The key steps were a modified palladium-catalyzed coupling of an aryl iodide with methyl 2-acetamidoacrylate and hydrogenation of the resulting sterically hindered dehydroamino acid 4 using [Rh(1,5-COD)- ( R , R -DIPAMP)]BF 4 as catalyst.",10.1055/s-1992-26212,1992-01-01,0.6378232785165329
Organic Process Research & Development,An Expedient Synthesis of 6α-Fluoroursodeoxycholic Acid,"Optimization of the synthesis of 6α-fluoroursodeoxycholic acid 1 is described starting from the commercially available 2 . The penultimate intermediate 16 was made in eight synthetic steps but in only four operations in an overall yield of 57%. The highlights are flourination of hydroxyketo acid 11 using Selectfluor through the intermediacy of silyl enol ether 12, conversion of 13 to 14 via equilibration of fluoroketone, esterification, and acylation. The drug substance 1 was prepared from mesylate 16 using potassium superoxide followed by a mild reductive workup using methoxydiethylborane.",10.1021/op0255433,2002-07-16,0.6378231749007844
Synthesis,A Convenient Synthesis of (<i>Z</i>)-5-Undecen-2-one: A Pheromone from the Pedal Gland of the Bontebok (<i>Damaliscus dorcas dorcas</i>),"All articles of this category Nitroaldol condensation, oxidation and denitration are the steps of a new synthetic scheme for the preparation of ( Z )-5-undecen-2-one in 54% overall yield.",10.1055/s-1986-31472,1986-01-01,0.6377982426211534
Organic Letters,Zirconocene-Mediated Synthesis of Cyclobutabenzenes,"A new, mild, one-pot method for the synthesis of cyclobutabenzenes by the zirconium-promoted cross-coupling reaction of aryllithium compounds and alkenyl bromides is reported. Formation of an arynezirconocene complex and its regioselective coupling with an alkenyl bromide are the key steps of the process. This method allows the regio- and diastereoselective synthesis of functionalized cyclobutabenzene derivatives from simple and easily available starting materials.",10.1021/ol801652h,2008-09-19,0.6377919092089245
Tetrahedron,An asymmetric synthesis of the key precursor to (−)-indolizomycin,,10.1016/s0040-4039(99)00728-5,1999-06-01,0.6377809648544868
Synthesis,A Short Synthesis of EnantiomericPhytoprostanes B<sub>1</sub> Type I,"The synthesis of both enantiomers of phytoprostane B1 type I from 3-[(dimethoxyphosphoryl)methyl]cyclopent-2-enone is reported. It consists of three steps including regioselective alkylation of the substrate at C(2) with methyl 8-bromooctanoate, subsequent Horner reaction with enantiomeric O-benzoyl-protected α-hydroxybutanals and final methanolysis. This affords the product in 25% overall yield.",10.1055/s-0029-1216883,2009-07-01,0.6377803419722854
Organic Letters,"A Unified Modular Synthetic Strategy for Dictyodendrins F, H, I, and G","A unified modular synthetic strategy has been developed for the first total synthesis of dictyodendrins G and synthesis of dictyodendrin F, H and I in 11 steps. The synthesis features consecutive functionalization of the core aminoquinone by palladium-mediated Suzuki-Miyaura coupling reaction, 1,4-addition, acylation and base mediated formation of a pyrrolinone, and the formation of carbazolequinone moiety through a formal [3 + 2] cycloaddition using arynes generated in situ. Several dictyodendrin analogues were also synthesized using this strategy.",10.1021/acs.orglett.7b02511,2017-08-28,0.6377737234460576
Tetrahedron,"Novel triethylsilane mediated reductive N -alkylation of amines: improved synthesis of 1-(4-imidazolyl)methyl-4-sulfonylbenzodiazepines, new farnesyltransferase inhibitors",,10.1016/s0040-4039(00)02257-7,2001-02-01,0.6377586130464004
Organic Letters,First Enantioselective Total Synthesis of (+)-(<i>R</i>)-Pinnatolide Using an Asymmetric Domino Allylation Reaction,An efficient total synthesis of (+)-(R)-Pinnatolide is described. As a key step an asymmetric multicomponent domino allylation reaction of methyl levulinate is used to form the quaternary stereogenic center in a highly selective way.,10.1021/ol301932d,2012-08-02,0.6377537908256212
Angewandte Chemie International Edition,Enantioselective Synthesis of Kedarcidin Chromophore Aglycon in Differentially Protected Form,"Four components, each prepared in multigram amounts, have been assembled in the convergent (25 steps in the longest linear sequence), enantioselective synthesis of the differentially protected kedarcidin chromophore aglycon (1). In addition to the enantioselective synthesis of each of the four components, the route features a transannular anionic cyclization to form the bicyclo[7.3.0]dodecadienediyne core in the presence of an ansa-bridged macrolactone. MOM=methoxymethyl, TIPS=triisopropylsilyl, TES=triethylsilyl.",10.1002/1521-3773(20020315)41:6<1062::aid-anie1062>3.0.co;2-8,2002-03-15,0.6377385937040355
Organic Letters,Total Synthesis of (−)-Kopsifoline A and (+)-Kopsifoline E,"We report the first total synthesis of (-)-kopsifoline A and (+)-kopsifoline E. Our synthetic strategy features a biogenetically inspired regioselective C17-functionalization of a versatile intermediate containing the pentacyclic core of aspidosperma alkaloids. The vinylogous urethane substructure of this intermediate affords (-)-kopsifoline D via C3-C21 bond formation under the Mitsunobu reaction conditions, while it enables selective C17-functionalization en route to (-)-kopsifoline A and (+)-kopsifoline E.",10.1021/acs.orglett.1c03448,2021-11-12,0.637735804598847
Synlett,Synthesis of Dehydromuscone by an Alkene Metathesis Macrocyclization Reaction at 0.2 M Concentration,Abstract The industrial fragrance compound dehydromuscone was synthesized in five linear steps and 19% overall yield. The synthesis features a highly efficient nondiluted ring-closing metathesis macrocyclization reaction as a key step that proceeds at a 0.2 M concentration in the presence of 0.1 mol% Nitro-Grela catalyst. The synthesis employs commercially available linear starting materials and is shorter by at least two steps than the current industrial synthesis route.,10.1055/a-1932-9317,2022-08-29,0.6377265552423481
Tetrahedron,Stereocontrolled synthesis of the key intermediate for the enantioselective synthesis of clerodane natural products,,10.1016/s0040-4039(97)01614-6,1997-09-01,0.6377237705567035
Organic Letters,Total Synthesis of the Phosphorylated Zwitterionic Trisaccharide Repeating Unit of <i>Photorhabdus temperata cinerea</i> 3240,"Herein, we report the total synthesis of the phosphorylated zwitterionic trisaccharide repeating unit of Photorhabdus temperata subsp. cinerea 3240. The efficient route involves regio- and stereoselective assembly of trisaccharide with rare deoxyamino sugar AAT at the nonreducing end, late stage oxidation, and installation of a phosphate linker on the trisaccharide. The total synthesis was completed via a longest linear sequence of 24 steps in 6.5% overall yield.",10.1021/acs.orglett.1c02487,2021-08-30,0.6377074296725419
Tetrahedron,Towards the synthesis of prevezol C: total enantioselective synthesis of (−)-2-epi-prevezol C,,10.1016/j.tetlet.2010.07.019,2010-07-09,0.6376635343537987
Journal of the American Chemical Society,Total Synthesis of Etnangien,"The first total synthesis of the potent RNA-polymerase inhibitor etnangien is described, which establishes unequivocally the relative and absolute configuration of this sensitive macrolide antibiotic. Key features of the expedient and modular synthesis include stereoselective substrate-controlled boron- and tin-mediated aldol couplings to set the characteristic sequences of methyl and hydroxyl bearing stereogenic centers with high degrees of stereoselectivity and yield, an efficient Heck macrocyclization of a conformationally restricted substrate, and a late-stage introduction of the labile side chain. The convergent approach should be amenable to designed analogues.",10.1021/ja9056163,2009-07-31,0.6376300187134744
Angewandte Chemie International Edition,"Cyclization of Pyrene Oligomers: Cyclohexa‐1,3‐pyrenylene","First synthesis of the macrocycle cyclohexa(1,3-pyrenylene) is achieved in six steps starting with pyrene, leading to a non-aggregating highly twisted blue-light-emitting material. The cyclodehydrogenation of the macrocycle offers a promising synthesis route to holey-nanographene.",10.1002/anie.201508180,2015-11-06,0.6376109829244593
Synlett,Stereoselective Synthesis of Novel Chimerical Amino Acids via a Photochemical Key Step,"All articles of this category The synthesis of novel chimerical amino acid derivatives 6-8 bearing the 6-azatricyclo[3.3.1.0 3,7 ]nonane (methanotropane)skeleton is described. Starting with one chirality centre in L-4-oxoprolines 2 we succeeded in the fully stereoselective introduction of four new chirality centres. The key step of our synthetic route is a photochemical cyclization of phenyl ketones, whose stereoselectivity has been explained by the different stability of the triplet biradical conformers. amino acid - stereoselective synthesis - cyclizations - photochemistry - radical reactions",10.1055/s-1999-2843,1999-09-01,0.6376081713928152
Organic Letters,Asymmetric Synthesis of the AB Ring System of Lactonamycin,[reaction: see text] An enantiospecific synthesis of the AB fragment of lactonamycin (5) is achieved in eight steps from dimethyl D-tartrate. Ester enolate chemistry features prominently in the sequence.,10.1021/ol047922h,2004-11-23,0.6375985719086514
Journal of Organic Chemistry,A Route to the Heterocyclic Cluster of the E-Series of Thiopeptide Antibiotics,A concise route to the 3-hydroxypyridine core of thiopeptide antibiotics such as nocathiacin is described. Key phases of the sequence involve a modified Hantzsch pyridine construction and a chemoselective Peng deprotection of a phenolic MOM ether.,10.1021/acs.joc.5b00315,2015-04-02,0.6375864946666512
Tetrahedron,"An efficient route to pyridine and 2,2′-bipyridine macrocycles incorporating a triethylenetetraminetetraacetic acid core as ligand for lanthanide ions",,10.1016/j.tetlet.2009.09.030,2009-09-10,0.6375717000994459
Angewandte Chemie International Edition,Total Synthesis of (−)‐Acetylaranotin,The key step in this total synthesis of (-)-acetylaranotin is the efficient formation of the characteristic dihydrooxepine ring from cyclohexenone through an unusual vinylogous Rubottom oxidation and a regioselective Baeyer-Villiger oxidation. (-)-Acetylaranotin is obtained in 22 steps from commercially available L-Cbz-tyrosine (Cbz=benzyloxycarbonyl).,10.1002/anie.201207307,2012-11-19,0.6375713437940598
Organic Letters,Total Syntheses of (±)-Melicolones A and B,"The first total syntheses of (±)-melicolones A and B, which have a unique and densely functionalized framework derived from a rearranged prenylated acetophenone, were accomplished in 12.3% combined overall yield. The concise and divergent synthesis of these two natural products, which were isolated in racemic form, was achieved in a longest linear sequence requiring only 9 steps (11 total steps) and 8 isolated intermediates using commercially available starting materials. This approach, which might enable access to all tetracyclic melicolones, features the highly regioselective (16:1) and diastereoselective (15:1) dipolar cycloaddition of a carbonyl ylide generated by the unusual cyclization of a rhodium carbene with the carbonyl oxygen atom of an aliphatic aldehyde. This cycloaddition proceeds with dominant steric control to give a highly functionalized oxabicycloheptane core. Stereoselective enolate alkylation led to a prenylated intermediate that underwent an intramolecular aldol reaction to give the penultimate tricyclic intermediate. Tandem epoxidation of the pendant prenyl group followed by a regioselective, acid-catalyzed cyclization delivered (±)-melicolones A and B.",10.1021/acs.orglett.0c03454,2020-11-02,0.6375673455958153
Angewandte Chemie International Edition,Total Synthesis of (+)‐Omphadiol,"A smooth transition from (R)-carvone to a β-lactone and then to (+)-omphadiol characterizes the first total synthesis of this sesquiterpene, which was achieved in ten steps and 18 % overall yield. All six contiguous stereogenic centers were introduced in a highly diastereoselective manner. Key steps include a nucleophile-promoted aldol lactonization, a single-pot, sequential intra-/intermolecular dialkylation, a tandem olefin isomerization/RCM, and a cyclopropanation with unusual facial selectivity.",10.1002/anie.201102289,2011-07-14,0.6375599914134602
Organic Process Research & Development,Overall Synthesis of GSK356278: Quick Delivery of a PDE4 Inhibitor Using a Fit-for-Purpose Approach,"The family of phosphodiesterase (PDE) enzymes hydrolyse cyclic nucleotides, cAMP and cGMP, leading to their inactivation as intracellular second messengers. Inhibition of these enzymes leads to an elevation of levels of cyclic nucleotides in the cell and prolongs their action on downstream signaling pathways. PDE4, of which there are four subtypes, is widely expressed throughout the brain but is also abundant in the periphery in inflammatory and immune cells, in the gastrointestinal tract, and in cardiac myocytes. GSK356278 1 is a potent, selective, and competitive inhibitor of PDE4 enzymes currently under investigation for the treatment of CNS disorders. The initial synthetic route developed by Medicinal Chemistry Department, used several hazardous and/or expensive reagents and harsh conditions and gave relatively low yields. By targeted process of research and development plus application of analytical techniques to identify byproduct and extensive route scouting, a novel synthetic route for 1 has been developed. This contribution reports the optimisation of the chemical synthesis of 1 to develop a large-scale process suitable for its synthesis.",10.1021/op1001148,2010-07-01,0.6375501899294206
Journal of Organic Chemistry,Hydrogen-Atom Abstraction/Cyclization in Synthesis. Direct Syntheses of Coumestan and Coumestrol,"The synthesis of coumestrol has been achieved in five steps from 1, 3-dimethoxybenzene. The key step is a photochemical cyclization of a glyoxylate ester.",10.1021/jo0004198,2000-08-11,0.6375436916249612
Synthesis,An Improved and Scalable Synthesis of the Potent SREBP Inhibitor KK-052 via [3+2] Cycloaddition,"Abstract KK-052 is a novel vitamin-D-based selective sterol regulatory element-binding protein (SREBP) suppressor that lacks vitamin D genomic activity mediated through the vitamin D receptor in both in vitro and in vivo settings. In our initial synthetic effort, KK-052 was produced as one of the structural isomers obtained via the Mitsunobu reaction involving a CD-ring allyl alcohol and 5-phenyl-1H-tetrazole. In this work, we present a refined methodology for enhancing the selective synthesis of KK-052 through a [3+2] cycloaddition between a CD-ring benzimidoyl chloride and sodium azide, a technique that proved amenable to gram-scale production. Additionally, this synthetic method permitted the production of a more potent m-methyl analogue of KK-052.",10.1055/a-2236-0413,2023-12-28,0.6375403390754134
Organic Letters,Total Synthesis of (+)-Crocacin D,"[structure: see text] The first asymmetric synthesis of (+)-crocacin D (4) is described. The key steps in the sequence are the stereoselective assembly of the stereotetrad via a substrate-controlled aldol reaction and anti-selective reduction, formation of the (E,E)-diene by a Stille cross-coupling between the stannane 8 and vinyl iodide 9, and the acylation of (Z)-enecarbamate 6 with the acid chloride derived from polyketide fragment 16 which introduced the (Z)-enamide functionality.",10.1021/ol017092x,2002-01-22,0.63753544585702
Organic Letters,"New, Abridged Pathway to Masamune's “Southern Hemisphere” Intermediate for the Total Synthesis of Bryostatin 7","[reaction: see text] The ""Southern Hemisphere"" intermediate 2, used by Masamune and co-workers for their asymmetric total synthesis of bryostatin 7 (1), has been synthesized from (E)-1,4-hexadiene (11) by a 24-step pathway that has a longest linear sequence of only 20 steps. This is the shortest synthesis of 2 so far recorded, and moreover, it is fully stereocontrolled.",10.1021/ol027393m,2003-01-23,0.6375111996211289
Organic Process Research & Development,"Industrial Synthesis of Maxacalcitol, the Antihyperparathyroidism and Antipsoriatic Vitamin D<sub>3</sub> Analogue Exhibiting Low Calcemic Activity","Maxacalcitol, the 22-oxa-derivative of 1α,25-dihydroxyvitamin D 3 and used currently as an antihyperparathyroidism and antipsoriatic drug, has been synthesized in seven chemical steps from 1α-hydroxydehydroepiandrosterone on the basis of our previously developed route. The present synthesis allows the production of the protected form of the penultimate intermediate in 26% overall yield in a kilogram scale reaction employing neither difficult reaction conditions nor chromatographic purification, having overcome all the difficulties involved in the previous route.",10.1021/op049822x,2005-04-29,0.6374862042068462
Tetrahedron,"A new synthesis of indolo[2,3-α]quinolizidine derivatives: a formal total synthesis of (±)-geissoschizine",,10.1016/s0040-4039(01)90396-x,1981-01-01,0.637477206228468
Journal of Organic Chemistry,Enantioselective Synthesis of a Fluorinated Analogue of the Orsellinic Acid-Type Twelve-Membered Lactone Lasiodiplodin,"The chemoenzymatic synthesis of the racemate and the one enantiomer of the fluorinated analogue 8 of the natural cyclooxygenase inhibitor lasiodiplodin is decribed. A lipase-mediated deracemization of the fluorohydrin 18 provided the chiral, nonracemic building block for the enantioselective synthesis of the title compound. The key step was the formation of the 12-membered lactone by a ring-closing metathesis.",10.1021/jo0012445,2000-11-14,0.6374728582554297
Tetrahedron,Studies in macrolide synthesis: A concise asymmetric synthesis of a macrolide intermediate for the erythronolides.,,10.1016/s0040-4039(00)80325-1,1988-01-01,0.6374629498086003
Organic Letters,Isoquinoline Synthesis by Heterocyclization of Tosylmethyl Isocyanide Derivatives: Total Synthesis of Mansouramycin B,A new method for the synthesis of isoquinolines through a catalytic acid-mediated cyclization of α-benzyl TosMIC derivatives has been developed. This methodology has been successfully applied to the total synthesis of mansouramycin B. This is the first total synthesis of this compound to be reported in the literature.,10.1021/ol5032624,2014-12-18,0.6374548115479823
Synthesis,A Facile Synthesis of CD45 Protein Tyrosine Phosphatase Inhibitor Marine Natural Product Pulchellalactam,"A facile five-step route to the naturally occurring CD45 protein tyrosine phosphatase inhibitor, (Z)-pulchellalactam, with 64% overall yield has been demonstrated starting from citraconimide (5) via regioselective NaBH4 reduction, catalytic hydrogenation, resin-catalyzed dehydration, N-BOC protection, and stereoselective condensation pathway.",10.1055/s-2004-822407,2004-06-16,0.6374536385528835
Synlett,"Combinatorial Synthesis of 5-Aryl-[1,2,4]-triazolo-[1,5-a]-pyridine Derivatives as Potential Inhibitors of the Adenosine 2A Receptor","All articles of this category A novel and efficient 4-step synthesis of 2,4-diamino-4-bromo-pyridine 4 in 56% overall yield by a double Curtius rearrangement as a key step is reported. N -amination of 2,4-diamino-4-bromo-pyridine 4 with O -mesitylenesulfonylhydroxylamine 10 and subsequent reaction with aldehydes yielded, upon oxidative ring-closure, 5-bromo-triazolopyridines 2a-2f . Thereafter, from a combinatorial parallel Suzuki cross-coupling reaction 260 previously non-described 5-aryl-[1,2,4]-triazolo-[1,5-a]-pyridines 1 were obtained in acceptable overall yield. Adenosine 2A - double-Curtius rearrangement - N -amination - Suzuki cross-coupling reaction - 7-amino-triazolopyridine derivatives",10.1055/s-2001-18758,2001-01-01,0.6374513542295135
Journal of Organic Chemistry,Diastereoselective Intramolecular Heck Reaction Assisted by an Acetate Group: Synthesis of the Decahydrobenzofluorene Derivative Dasyscyphin E,"The first synthesis of antifungal sesquiterpene quinol dasyscyphin E was achieved starting from trans-communic acid. The process described involves the first diastereoselective synthesis of this type of compound by cyclization of an aryl bicyclosesquiterpene. The acid was efficiently transformed into a sesquiterpene synthon, which was converted into the corresponding bromoaryl sesquiterpene. The key step of synthetic sequence was the cyclization of the latter under Heck reaction conditions, which yielded the tetracyclic skeleton of the target compound with complete diastereoselectivity. The participation of an acetate group is decisive, both for the course of the Heck reaction and for the stereoselectivity of the process.",10.1021/acs.joc.7b01551,2017-08-15,0.6374189698759115
Journal of Organic Chemistry,Methodology for the Preparation of 2-Argininylbenzothiazole,"An efficient process to produce kilogram quantities of a key argininylbenzo[d]thiazole intermediate was developed for the preparation of the tryptase inhibitor RWJ-56423. A variety of activated arginine esters and benzo[d]thiazole nucleophiles were evaluated as coupling partners. Our work led to the selection and optimization of an argininyl imidazolide ester and benzothiazol-2-yl MgCl nucleophile. This paper focuses on the preparation, use, and stability of the benzothiazol-2-yl Grignard reagents.",10.1021/jo7019543,2007-11-13,0.6373873046910019
Journal of the American Chemical Society,Synthesis of (−)-Quinocarcin by Directed Condensation of α-Amino Aldehydes,"An enantioselective synthesis of the natural antiproliferative agent quinocarcin was achieved by the directed condensation of optically active alpha-amino aldehyde intermediates. Condensation of the N-protected alpha-amino aldehyde 1, prepared in eight steps (19% yield) from (R,R)-pseudoephedrine glycinamide, with the C-protected alpha-amino aldehyde derivative 2, prepared in seven steps (34% yield) from (R,R)-pseudoephedrine glycinamide, afforded the corresponding imine in quantitative yield. Without isolation, direct treatment of this imine intermediate with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and hydrogen cyanide led to cleavage of the fluorenylmethoxycarbonyl (Fmoc) protective group followed by addition of cyanide (Strecker reaction) to form the bis-amino nitriles 3 as a mixture of diastereomers, in 91% yield. Treatment of the diastereomers 3 with trimethylsilyl cyanide and zinc chloride in 2,2,2-trifluoroethanol at 60 degrees C led to stepwise cyclization to form the tetracyclic product 4 (42% yield from 1 and 2). The latter intermediate was transformed into (-)-quinocarcin (1) in five steps (45% yield). The yield of quinocarcin was 19% from 1 and 2 (7 steps), and 4% from pseudoephedrine glycinamide (15 steps).",10.1021/ja056206n,2005-11-10,0.6373701034213392
Organic Letters,"Asymmetric Total Syntheses of Colchicine, β-Lumicolchicine, and Allocolchicinoid<i>N</i>-Acetylcolchinol-<i>O</i>-methyl Ether (NCME)","A concise and highly enantioselective synthesis of colchicine (>99% ee) in eight steps and 9.3% overall yield, without the need for protecting groups, was developed. A unique Wacker oxidation was used for enabling regioselective construction of the highly oxidized and synthetic challenging tropolone C-ring. Furthermore, asymmetric syntheses of β-lumicolchicine and N-acetylcolchinol-O-methyl ether (NCME) were achieved. Notably, NCME was synthesized from β-lumicolchicine by an unusual decarbonylation and electrocyclic ring-opening cascade reaction.",10.1021/acs.orglett.7b02224,2017-08-19,0.6373612376015847
European Journal of Organic Chemistry,Short Access to the Aromadendrane Family: Highly Efficient Stereocontrolled Total Synthesis of (±)‐Cyclocolorenone and (±)‐α‐Gurjunene,"Abstract (±)‐Cyclocolorenone ( 2 ), an aromadendrane, was prepared stereoselectively in seven steps in 10.8–12.5 % overall yield from the commercially available tropylium cation via key intermediate 6 , which was used as a general and efficient precursor to bicyclo[5.3.0]decane sesquiterpenes. (±)‐α‐Gurjunene ( 3 ) was obtained through the efficient deoxygenation of (±)‐ 2 , constituting therefore the first total synthesis of this natural product in eight steps from the tropylium cation. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2009)",10.1002/ejoc.200900253,2009-05-14,0.6373523470495546
Tetrahedron,A mercury mediated route to the mitosenes,,10.1016/s0040-4039(01)82026-8,1981-01-01,0.6373330378464892
Organic Letters,Chirality Transfer and Asymmetric Catalysis: Two Strategies toward the Enantioselective Formal Total Synthesis of (+)-Gelsenicine,"Two strategies are described en route to an enantioselective total synthesis of gelsenicine. One approach centers on a chirality transfer cycloisomerization that ultimately fell short. Separately, an asymmetric catalysis route utilizing bisphosphine-gold-catalyzed cycloisomerization was pursued. A catalytic system was identified that provided a synthetic intermediate in our Gelsemium alkaloid syntheses in high enantiopurity and with absolute configuration determined by electronic circular dichroism, thus representing an enantioselective formal total synthesis of (+)-gelsenicine.",10.1021/acs.orglett.2c01974,2022-07-07,0.6373103095162731
Journal of the American Chemical Society,"Catalytic Enantioselective Peroxidation of α,β-Unsaturated Aldehydes for the Asymmetric Synthesis of Biologically Important Chiral Endoperoxides","We have developed an unprecedented highly enantioselective catalytic peroxidation of enals. Critical to this development is the discovery that varying the structure of the hydroperoxide has a significant impact on the enantioselectivity of the organocatalytic asymmetric peroxidation. This novel transformation enabled the development of an enantioselective route toward the core structure shared by all members of the stolonoxide family of anticancer natural products, a connected trans-3,6-disubstituted-1,2-dioxane and trans-2,5-disubstituted-tetrahydrofuran ring system. Our route also features an unprecedented cyclization cascade of a chiral bis(epoxy)hydroperoxide. The new methodology and synthetic strategy established in this work should be applicable to the enantioselective synthesis of a broad range of chiral 1,2-dioxolanes and 1,2-dioxanes, thereby facilitating biological and medicinal chemistry studies of peroxy natural products.",10.1021/jacs.5b05345,2015-06-23,0.6372965160874854
Organic Letters,Total Synthesis of Pentosidine,"Pentosidine, a biologically important advanced glycation endproduct, has been accessed in a rapid, high-yielding manner. The synthesis was accomplished via a six-step sequence starting with 3-amino-2-chloropyridine and features a palladium-catalyzed tandem cross-coupling/cyclization to construct the imidazo[4,5-b]pyridine core.",10.1021/ol3021226,2012-08-21,0.6372792200400211
Organic Process Research & Development,Process Development for the Manufacture of a Topical Pan-Trk Inhibitor Incorporating Decarboxylative sp<sup>2</sup>–sp<sup>3</sup> Cross-Coupling,"The development of a synthetic route toward topical pan-Trk inhibitor 1 is described as an eight-stage synthesis from available starting materials. Process improvements include the development of a decarboxylative sp 2 –sp 3 cross-coupling which had not previously been demonstrated on scale. Parameters were explored, balancing the safety aspects with conversion and selectivity, scaling up in a stepwise fashion to multiple successful 0.7 kg batches. The cross-coupling showed high diastereoselectivity, with the opposite diastereomer not observed in the crude 19 F NMR. Selectivity was further improved by crystallizing the downstream pyrrolidine salt after Boc deprotection, to give a diastereomer ratio of 99.5:0.5 by UPLC. This route has been reproducibly demonstrated in two GMP campaigns delivering API on kilogram scale, in >98% area purity by HPLC. The route design, solid-form screening, process research, and manufacture have enabled crucial first-in-human (FIH) clinical studies, through focus on speed of delivery.",10.1021/acs.oprd.4c00325,2024-11-12,0.6372658440476232
Tetrahedron,An improved amide coupling procedure for the synthesis of N-(pyridin-2-yl)amides,,10.1016/j.tetlet.2009.02.071,2009-02-15,0.6372631566245662
Journal of the American Chemical Society,"Concise Total Synthesis of Trichodermamides A, B, and C Enabled by an Efficient Construction of the 1,2-Oxazadecaline Core","We report herein a facile and efficient method of the construction of the cis-1,2-oxazadecaline system, distinctive of (pre)trichodermamides, aspergillazine A, gliovirin, and FA-2097. The formation of the 1,2-oxazadecaline core was accomplished by a 1,2-addition of an αC-lithiated O-silyl ethyl pyruvate oxime to benzoquinone, which is followed by an oxa-Michael ring-closure. The method was successfully applied to the concise total synthesis of trichodermamide A (in gram quantities) and trichodermamide B, as well as the first synthesis of trichodermamide C.",10.1021/jacs.5b05205,2015-06-18,0.637261557939736
Journal of the American Chemical Society,Enantioselective Synthesis of Euonyminol,"We describe an enantioselective total synthesis of the nonahydroxylated sesquiterpenoid euonyminol, the dihydro-β-agarofuran nucleus of the macrocyclic terpenoid alkaloids known as the cathedulins. Key features of the synthetic sequence include a highly diastereoselective intramolecular alkene oxyalkylation to establish the C10 quaternary center, an intramolecular aldol–dehydration to access the tricyclic scaffold of the target, a tandem lactonization–epoxide opening to form the trans -C2–C3 vicinal diol residue, and a late-stage diastereoselective α-ketol rearrangement. The synthesis provides the first synthetic access to enantioenriched euonyminol and establishes a platform to synthesize the cathedulins.",10.1021/jacs.0c12998,2021-01-07,0.6372480627998051
Organic Process Research & Development,Scalable Process of Methimazole,"Base hydrolysis of imidazole carboxylate was observed to be an efficient route for the scalable synthesis of the antithyroid drug methimazole. Ethyl 3-methyl-2-thioxo-2,3-dihydro-1H-imidazole-1-carboxylate ( 12 ) was produced as a key intermediate in the reaction of 1-methyl-1H-imidazole ( 4 ) with ethyl chloroformate ( 11 ) and sulfur. Compound 12 undergoes hydrolysis in two steps in the presence of a base to give methimazole ( 1 ) with an overall yield of 78%. The process was studied through the Quality by Design (QbD) concept and observed to be robust.",10.1021/acs.oprd.2c00185,2022-12-15,0.6372200405356737
Tetrahedron,A new and efficient route to the synthesis of pyrazole and pyrimidine C-nucleoside derivatives,,10.1016/s0040-4039(98)00631-5,1998-05-01,0.6372127171200713
Angewandte Chemie International Edition,"Total Synthesis of the Macrolide Antibiotic 5,6-Dihydrocineromycin B","Three building blocks are coupled convergently in the first total synthesis of the macrolide antibiotic 5,6-tetrahydrocineromycin B (1); the facial selective allylation of a methyl ketone is the key step of the synthesis. TBDMS=tert-butyldimethylsilyl, PMB=p-methoxybenzyl.",10.1002/1521-3773(20010302)40:5<901::aid-anie901>3.0.co;2-f,2001-03-02,0.6371785072693872
Organic Letters,"Total Synthesis of a New Cytotoxic Acetogenin, Jimenezin, and the Revised Structure","The first total synthesis of jimenezin was achieved by using carbohydrates as chiral building blocks, thus revising the proposed structure 1 to 2. The key steps in this synthesis include an efficient construction of the THP-THF fragments 3 and 16 through a stereoselective condensation between the pyranyl aldehyde 5 and the acetylene derivative 6, and a palladium-catalyzed coupling reaction of 3 or 16 with a terminal butenolide 4.",10.1021/ol991200m,1999-11-17,0.6371721937758674
Journal of Organic Chemistry,Diastereoselective Synthesis of an Isoprostane:<b> (</b>±)-8-<i>epi</i>-PGF<sub>2</sub><sub>α</sub> Ethyl Ester,"A total synthesis of the isoprostane (+/-)-8-epi-PGF(2)(alpha) ethyl ester (5) is described, based on the diastereoselective cyclization of alpha-diazo ketone 7. This ketone is assembled by aldol condensation between alpha-diazo ketone 8 and aldehyde 9. The sequential alpha-diazo ketone aldol/insertion described here offers a powerful new approach to cycloalkane construction.",10.1021/jo9616365,1997-01-01,0.6371664207416463
Synlett,Molecular Iodine Assisted Electrocyclisation: Synthesis of Arcyriaflavin A and Formal Synthesis of Staurosporinone,"A new method for the synthesis of the indolocarbazole alkaloid arcyriaflavin A is described. The synthetic strategy employs a graphite-catalysed alkenation, one-pot oxidation–Wittig reaction, iodine-catalysed electrocyclisation and nitrene insertion as the key steps. The strategy also constitutes a formal synthesis of another indolocarbazole alkaloid staurosporinone.",10.1055/s-0034-1378536,2014-08-06,0.6371530790762595
Synthesis,Synthesis of (<i>Z</i>)-2-(2<i>H</i>-Isoquinolin-1-ylidene)acetamides by Iodine-Mediated Cyclization of (<i>Z</i>)-3-Amino-3-(2-vinylphenyl)propenamides,"(Z)-2-(2-Acetyl-2H-isoquinolin-1-ylidene)acetamides have been synthesized from 2-vinylbenzonitrile derivatives in three steps. The key step involves the iodine-mediated 6-endo cyclization of (Z)-3-acetylamino-3-(2-vinylphenyl)propenamides, which are prepared by the coupling of 2-vinylbenzonitriles with magnesium enolates of tertiary amides followed by N-acetylation.",10.1055/s-2007-965934,2007-03-01,0.6371462684344514
Organic Letters,Forging the Tetracyclic Core Framework of Rhodomolleins XIV and XLII: A Ring-Distortion Approach,"A ring distortion approach for the synthesis of an advanced intermediate en route to rhodomolleins XIV and XLII was described, which led to successful construction of the 5/8/5/5 tetracyclic core framework of the kalmane diterpenoids. Key steps of the strategy include an oxidative dearomatization-induced (ODI)-Diels-Alder cycloaddition, a Dowd-Beckwith rearrangement, and a bioinspired Wagner-Meerwein rearrangement.",10.1021/acs.orglett.4c00885,2024-04-24,0.6371355153519979
Chemical Science,"A bioinspired, one-step total synthesis of peshawaraquinone",A new proposal for the biosynthesis of peshawaraquinone via the unsymmetrical dimerization of dehydro-α-lapachone led to its total synthesis in one step from inexpensive starting materials.,10.1039/d2sc05377b,2022-12-21,0.6371267410086617
Organic Letters,Toward a Total Synthesis of Peloruside A:  Enantioselective Preparation of the C8−C19 Region,"An efficient synthetic sequence toward the C8-C19 region of peloruside A has been developed. The route is highlighted by a selective electrophilic cyclization reaction, a single-step epoxide ring-opening/methylation sequence, and a stereoselective Mukaiyama aldol reaction. [reaction: see text]",10.1021/ol0358814,2003-11-25,0.6371265773900584
Organic Letters,Asymmetric Total Synthesis of Biphenylquinolizidine Alkaloids 4″-<i>O</i>-Demethyllythridine and 14-<i>epi</i>-4″-<i>O</i>-Demethyllythridine,The first asymmetric total synthesis of new biphenylquinolizidine alkaloids 4″- O -demethyllythridine and 14- epi -4″- O -demethyllythridine isolated from Heimia salicifolia was accomplished. The key steps in the synthesis were a copper(I)-catalyzed asymmetric intramolecular aza-Michael reaction to build a chiral 4-arylquinolizidine unit and an intramolecular Suzuki–Miyaura cross-coupling reaction to construct a macrolactone ring comprising a biphenyl moiety.,10.1021/acs.orglett.9b02962,2019-09-16,0.6371189111020927
Journal of the American Chemical Society,Evolution of an Efficient and Scalable Nine-Step (Longest Linear Sequence) Synthesis of Zincophorin Methyl Ester,"Because of both their synthetically challenging and stereochemically complex structures and their wide range of often clinically relevant biological activities, nonaromatic polyketide natural products have for decades attracted an enormous amount of attention from synthetic chemists and played an important role in the development of modern asymmetric synthesis. Often, such compounds are not available in quantity from natural sources, rendering analogue synthesis and drug development efforts extremely resource-intensive and time-consuming. In this arena, the quest for ever more step-economical and efficient methods and strategies, useful and important goals in their own right, takes on added importance, and the most useful syntheses will combine high levels of step-economy with efficiency and scalability. The nonaromatic polyketide natural product zincophorin methyl ester has attracted significant attention from synthetic chemists due primarily to the historically synthetically challenging C(8)-C(12) all-anti stereopentad. While great progress has been made in the development of new methodologies to more directly address this problem and as a result in the development of more highly step-economical syntheses, a synthesis that combines high levels of step economy with high levels of efficiency and scalability has remained elusive. To address this problem, we have devised a new synthesis of zincophorin methyl ester that proceeds in just nine steps in the longest linear sequence and proceeds in 10% overall yield. Additionally, the scalability and practicability of the route have been demonstrated by performing all of the steps on a meaningful scale. This synthesis thus represents by a significant margin the most step-economical, efficient, and practicable synthesis of this stereochemically complex natural product reported to date, and is well suited to facilitate the synthesis of analogues and medicinal chemistry development efforts in a time- and resource-efficient manner.",10.1021/jacs.7b01590,2017-03-07,0.6371028579380656
Journal of the American Chemical Society,A Diosphenol-Based Strategy for the Total Synthesis of (−)-Terpestacin,"A novel diosphenol-based strategy has been developed for the enantioselective synthesis of (−)-terpestacin by multiple usage of the α-diketone functionality, first in the “Pd AAA−Claisen rearrangement” protocol, and second by the employment of its oxidized form, the ene-1,2-dione, as an excellent Michael acceptor. This synthesis demonstrates that the sequence of O-allylation−Claisen rearrangement provides a chemo- and regioselective enolate allylation, which can be performed asymmetrically with respect to the enolate or allyl fragment or both. In addition, many interesting chemoselectivity issues, including a highly selective RCM and a dihydroxylation, have been addressed. Overall, this synthesis was accomplished in 20 longest linear steps (24 total steps) from the inexpensive and commercially available 3-methyl-1,2-cyclopentanedione.",10.1021/ja070571s,2007-03-08,0.6370970136260267
Journal of Organic Chemistry,Synthesis of the DEF-Ring Spirocyclic Core of Cyclopamine,"A stereoselective synthesis of the DEF-ring spirocyclic core of cyclopamine was accomplished using commercially available materials. The key steps in the synthesis were (i) the enantioselective vinylogous Mannich reaction, followed by lactamization to generate the piperidine F ring, and (ii) intramolecular oxidative dearomative spiroetherification to construct the DEF-ring spirocyclic core of cyclopamine. We found that the stereochemistry of the spirocyclization was controlled by the configuration of the methyl group (C-20) in the substrate.",10.1021/acs.joc.3c02804,2024-02-23,0.6370946462715058
Journal of the American Chemical Society,11-Step Enantioselective Synthesis of (−)-Lomaiviticin Aglycon,"Lomaiviticins A and B are complex antitumor antibiotics that were isolated from a strain of Micromonospora. A confluence of several unusual structural features renders the lomaiviticins exceedingly challenging targets for chemical synthesis. We report an 11-step, enantioselective synthetic route to lomaiviticin aglycon. Our route proceeds by late-stage, stereoselective dimerization of two equivalent monomeric intermediates, a transformation that may share parallels with the natural products' biosyntheses. The route we describe is scalable and convergent, and it lays the foundation for determination of the mode of action of these natural products.",10.1021/ja200034b,2011-01-31,0.6370902407617595
Synlett,An Anionic Polycondensation Strategy for the Synthesis of Dibenzoxanthenones: Progress Toward the Synthesis of Hypoxyxylerone,An anionic polycondensation has been used as the key step in a highly convergent strategy for the preparation of hypoxy­xylerone derivatives.,10.1055/s-2004-835634,2004-11-08,0.6370891645714059
Journal of Organic Chemistry,"Total Synthesis and Structure Revision of (±)-Clavilactone D Through Selective Cyclization of an α,β-Dicarbonyl Peroxide","The structure of (±)-clavilactone D was revised, and the synthesis was achieved in seven steps from a substituted benzaldehyde. The key step was the base-catalyzed cyclization of an α,β-carbonyl peroxide, which was obtained by an iron-catalyzed three-component reaction of a benzaldehyde, an alkene, and TBHP. NaBH 4 -mediated reductive lactonization of the resulting cis -dicarbonyl epoxide led to the α,β-epoxy-γ-butyrolactone skeleton highly stereoselectively. The synthesis provides a concise, reliable, and practical route to the revised structure of clavilactone D.",10.1021/acs.joc.7b00693,2017-05-05,0.6370853805810592
Journal of Organic Chemistry,Total Synthesis of (−)-Cylindricine C,"(−)-Cylindricine C has been synthesized from commercially available ( S )-(−)-1,2,4-butanetriol in 11 steps with an overall yield of 12%. The key step utilizes a CrCl 2 reduction of an azide to form the corresponding amine with a subsequent double Michael addition to create the tricyclic skeleton of cylindricine from a monocyclic substrate.",10.1021/jo990363l,1999-06-11,0.637077481401104
Journal of Organic Chemistry,Asymmetric Total Synthesis of Gymnothespirolignan A via a Bioinspired Double Cyclization Approach,"The first asymmetric total synthesis of gymnothespirolignan A is disclosed in 11 steps. The salient feature of the synthesis is construction of the spirocyclic moiety through a bioinspired acid-promoted double cyclization of an acyclic gymnothebutyllignan A-like precursor, which involves a deprotection, hemiketalization, dehydrative oxonium formation, and Friedel-Crafts cyclization cascade transformation. This study provides a general approach to the asymmetric syntheses of novel spirocyclic gymnothelignans.",10.1021/acs.joc.4c03140,2025-03-03,0.6370464032455752
Journal of Organic Chemistry,Synthesis of (±)-Allocyathin B<sub>2</sub> and (+)-Erinacine A,"(±)-Allocyathin B 2 ( 2 ) and (+)-erinacine A ( 4 ), the 1-β- d -xyloside of (+)-allocyathin B 2, the first cyathin diterpenes to be prepared, have been synthesized using a carbonyl ene reaction of 14a to construct an appropriately functionalized seven-membered ring and palladium-catalyzed carbonylation of dienyl triflates 10 and 39 as key steps. The entire cyathin carbon skeleton is constructed in seven steps, and allocyathin B 2 is synthesized in only 17 steps (>5% overall yield) from readily available enone 9 .",10.1021/jo9804700,1998-06-12,0.6370275098366607
Tetrahedron,"An improved synthesis of 2-(1,2,4-thiadiazol-5-yl)pyridine by interception of an intermediate involved in a competing cyclisation reaction",,10.1016/j.tetlet.2007.04.140,2007-05-02,0.6370247346360377
Tetrahedron,"Synthesis of 2-methoxy-2-methyl-3-{6-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]pyridin-3-yl}propanoic acid, a dual PPARα/γ agonist",,10.1016/j.tetlet.2009.01.113,2009-01-27,0.6370202481057815
Tetrahedron,"Stannes in synthesis: A new route to 2-substituted-1,3-butadienes via stereoselective allyltin formation under homolytic conditions",,10.1016/s0040-4039(01)92967-3,1981-01-01,0.6369979527617722
Synlett,Asymmetric Synthesis of (+)-Methyl Epijasmonate and (-)-Methyl Curcurbate,"All articles of this category A short enantio- and diastereoselective synthesis of (+)-methyl epijasmonate 1 and (-)-methyl curcurbate 2 , two essential components of jasmin oil is described. The key step is a nickel catalyzed ring closure, which sets up three chiral centers with high diastereoselectivity. jasmonoids - catalytic enantioselective synthesis - nickel catalyzed carbozincation",10.1055/s-1995-4987,1995-05-01,0.6369828443398962
Tetrahedron,"A one-step route to 4-hydroxy-2,3-diaryl-3,4-dihydro-1 (2)-isoquinolones",,10.1016/s0040-4039(00)71138-5,1980-01-01,0.636975163899419
Journal of Organic Chemistry,"The Enantiospecific, Stereospecific Total Synthesis of the Ring-A Oxygenated Sarpagine Indole Alkaloids (+)-Majvinine, (+)-10-Methoxyaffinisine, and (+)-<i>N</i><sub>a</sub>-Methylsarpagine, as Well as the Total Synthesis of the <i>Alstonia</i> Bisindole Alkaloid Macralstonidine","The first stereospecific, enantiospecific total synthesis of the ring-A oxygenated sarpagine indole alkaloids (+)-N(a)-methylsarpagine (8), (+)-majvinine (14), and (+)-10-methoxyaffinisine (49), as well as the first total synthesis of the Alstonia bisindole alkaloid macralstonidine (9), has been accomplished. This approach employed the Schöllkopf chiral auxiliary for the stereospecific construction of the desired d-(+)-tryptophan unit required for the asymmetric Pictet-Spengler reaction. In addition, the strategy was doubly convergent for the enolate-mediated Pd(0) coupling process and the asymmetric Pictet-Spengler reaction can be employed to synthesize both macroline (2) and N(a)-methylsarpagine (8), the coupling of which provides macralstonidine (9). This approach to ring-A substituted alkoxyindole alkaloids should find wide application for the synthesis of other alkaloids for it is stereospecific and either enantiomer can be prepared with ease.",10.1021/jo030055u,2003-07-17,0.6369750084567273
Synthesis,"Indoloquinones, Part 7. Total Synthesis of the Potent Lipid Peroxidation Inhibitor Carbazoquinocin C by an Intramolecular Palladium-Catalyzed Oxidative Coupling of an Anilino-1,4-benzoquinone",All articles of this category (opens in new window),10.1055/s-2002-20953,2002-01-01,0.6369595061696443
Organic Letters,Formal Synthesis of (−)-Codeine by Application of Temporary Thio Derivatization,"Desymmetrization of a p-quinone monoacetal by organocatalytic sulfa-Michael addition provided rapid access to a C-ring building block for a formal synthesis of (-)-codeine. By means of a diastereoselective 1,2-addition for A/C-ring union, an intramolecular nitrone cycloaddition for construction of the phenanthrene core, and a sulfoxide elimination, an enantiopure key intermediate of the authors' previous synthesis of racemic codeine was available in 12 steps from isovanillin.",10.1021/acs.orglett.7b03972,2018-01-22,0.6369228742550551
Journal of the American Chemical Society,Tetrachlorovancomycin: Total Synthesis of a Designed Glycopeptide Antibiotic of Reduced Synthetic Complexity,"A technically straightforward total synthesis of a new class of vancomycin analogues of reduced synthetic complexity was developed that provided tetrachlorovancomycin ( 1, LLS = 15 steps, 15% overall yield) and its precursor aglycon 29 (nearly 20% overall yield). The class retains all the intricate vancomycin structural features that contribute to its target binding affinity and selectivity, maintains the antimicrobial activity of vancomycin, and achieves the simplification by an unusual addition, not removal, of benign substituents to the core structure. The modification, accomplished by addition of two aryl chloride substituents to provide 1, permitted a streamlined total synthesis of the new glycopeptide antibiotic class by removing the challenges associated with CD and DE ring system atropisomer stereochemical control. This also enabled their simultaneous and further-activated S N Ar macrocyclizations that establish the tricyclic skeleton of 1 . Key elements of the approach include catalyst-controlled diastereoselective formation of the AB biaryl axis of chirality (>30:1 dr), an essentially instantaneous macrolactamization of the AB ring system free of competitive epimerization (>30:1 dr), racemization free coupling of the E ring tetrapeptide, room temperature simultaneous CD and DE ring system cyclizations, a highly refined 4-step conversion of the cyclization product to the aglycon, and a protecting-group-free one-pot enzymatic glycosylation for disaccharide introduction. In addition to the antimicrobial evaluation of tetrachlorovancomycin ( 1 ), the preparation of key peripherally modified derivatives, which introduce independent and synergistic mechanisms of action, revealed their exceptional antimicrobial potency and provide the foundation for future use of this new class of synthetic glycopeptide analogues.",10.1021/jacs.3c08358,2023-09-18,0.6369070939684632
Tetrahedron,"An efficient synthesis of the novel dopamine autoreceptor antagonist S-(−)-OSU6162, via palladium catalyzed cross-coupling reaction",,10.1016/0040-4039(94)88428-5,1994-11-01,0.6368956672064774
Organic Letters,Total Synthesis of (−)-21-Isopentenylpaxilline,"[structure: see text] The total synthesis of (-)-21-isopentenylpaxilline (1) has been achieved. Key elements of the synthesis include the stereocontrolled construction of the advanced eastern hemisphere (-)-5, a highly efficient union of the eastern and western fragments (-)-5 and 4, respectively, exploiting our 2-substituted indole synthesis, and a new protocol for the construction of ring C.",10.1021/ol027575g,2003-01-28,0.636894818586401
Tetrahedron,"An efficient synthesis of 3-amino-2-arylimidazo[1,2-a]pyridines",,10.1016/j.tetlet.2008.05.134,2008-06-04,0.6368776407585486
Tetrahedron,"Efficient synthesis of (2R,3S)- and (2S,3S)-2-amino-1,3,4-butanetriols through stereodivergent hydroxymethylation of d-glyceraldehyde nitrones",,10.1016/s0040-4039(01)02191-8,2002-01-01,0.6368776407585486
Tetrahedron,Efficient synthesis of β-amino bromides,,10.1016/s0040-4039(00)00330-0,2000-04-01,0.6368776407585486
Organic Letters,Total Synthesis of Aspeverin via an Iodine(III)-Mediated Oxidative Cyclization,"The first total synthesis of aspeverin, a prenylated indole alkaloid isolated from Aspergillus versicolor in 2013, is described. Key steps utilized to assemble the core structure of the target include a highly diastereoselective Diels-Alder reaction, a Curtius rearrangement, and a unique strategy for installation of the geminal dimethyl group. A novel iodine(III)-initiated cyclization was then used to install the bicyclic urethane linkage distinctive to the natural product.",10.1021/ol5024163,2014-08-29,0.6368725633719887
Organic Letters,Total Syntheses of (+)-Vigulariol and (−)-Sclerophytin A,"The total syntheses of (+)-vigulariol and (-)-sclerophytin A are reported in 15 steps and 16 steps, respectively, from a known compound. The flexible, readily scalable synthetic strategy allows for rapid construction of a critical tricyclic intermediate and is demonstrated via the synthesis of these two marine natural products. A key reaction in this synthetic protocol is a combination Wittig/intramolecular Diels-Alder cycloaddition.",10.1021/ol201981j,2011-08-19,0.6368554309181634
Synthesis,"Total Synthesis of Protected D-<i>altro</i>- and D-<i>galacto</i>-3,6-Dideoxy-3-<i>C</i>-methylhexoses; Key Intermediates of a Rifamycin S Synthesis","All articles of this category Two particular derivatives of the title compound, used in the Kinoshita synthesis of the Rifamycin S ansa chain, were prepared by total synthesis from isobutyl ( R )-lactate. The best conditions were worked out for the inversion of the 2-hydroxy group in the appropriate α-D-allo- and β-D-talofuranosides, readily available with few steps from ( R )-2-benzyloxypropanal by the homoaldol reaction, with an α-metalated ( E )-2-butenyl carbamate.",10.1055/s-1989-27160,1989-01-01,0.6368406377706565
Tetrahedron,A new synthesis of 3-deoxy-d--2-octulosonic acid (kdo) from d-mannose,,10.1016/s0040-4039(00)61856-7,1987-01-01,0.6368300274712914
Tetrahedron,A new synthesis of d-ribose from l-glutamic acid,,10.1016/s0040-4039(01)96414-7,1971-01-01,0.6368300274712914
Tetrahedron,Fragmentation of carbohydrate anomeric alkoxy radicals. A new synthesis of alduronic acid lactones,,10.1016/0040-4039(96)00107-4,1996-03-01,0.6368300274712914
Tetrahedron,New synthesis of (±)-2-piperazinecarboxylic acid.,,10.1016/s0040-4039(00)74356-5,1991-11-01,0.6368300274712914
Tetrahedron,Synthesis of new triazamacrocycles N-functionalised with α-(S)-hydroxycarboxylic acid pendant-arms,,10.1016/s0040-4039(99)00875-8,1999-07-01,0.6368300274712914
Tetrahedron,New synthesis of pipecolic acid and analogs,,10.1016/0040-4039(81)80170-0,1981-01-01,0.6368300274712914
Tetrahedron,A new synthesis of lysergic acid,,10.1016/s0040-4039(00)81548-8,1983-01-01,0.6368300274712914
Tetrahedron,A new synthesis of 9-β-D-ribofuranosyluric acid and its 5′-monophosphate,,10.1016/s0040-4039(00)98224-8,1985-01-01,0.6368300274712914
Tetrahedron,A new synthesis of 3-deoxy-d-manno-2-octulosonic acid (KDO),,10.1016/s0040-4039(00)60683-4,1993-08-01,0.6368300274712914
Angewandte Chemie International Edition,Expeditious Total Synthesis of Hemiasterlin through a Convergent Multicomponent Strategy and Its Use in Targeted Cancer Therapeutics,"Hemiasterlin is an antimitotic marine natural product with reported sub-nanomolar potency against several cancer cell lines. Herein, we describe an expeditious total synthesis of hemiasterlin featuring a four-component Ugi reaction (Ugi-4CR) as the key step. The convergent synthetic strategy enabled rapid access to taltobulin (HTI-286), a similarly potent synthetic analogue. This short synthetic sequence enabled investigation of both hemiasterlin and taltobulin as cytotoxic payloads in antibody-drug conjugates (ADCs). These novel ADCs displayed sub-nanomolar cytotoxicity against HER2-expressing cancer cells, while showing no activity against antigen-negative cells. This study demonstrates an improved synthetic route to a highly valuable natural product, facilitating further investigation of hemiasterlin and its analogues as potential payloads in targeted therapeutics.",10.1002/anie.202010090,2020-09-25,0.6368234926811432
Organic Process Research & Development,Preparation of the HIV Attachment Inhibitor BMS-663068. Part 2. Strategic Selections in the Transition from an Enabling Route to a Commercial Synthesis,"During the process of developing a synthesis to a complex molecule, multiple decisions are made regarding the strategies and tactics used to prepare key bonds. In this article, we preface a series of papers describing the development of the commercial synthesis of BMS-663068 (a potential new treatment for HIV), with an in-depth discussion of the important strategic decisions made during the process of designing and demonstrating the proposed commercial synthesis of this complex clinical candidate. We discuss the key strategic disconnections and the key experimental data used to drive our tactical decisions during development. In the remaining articles in this series, we outline the development of these enabling chemical processes into scalable procedures ready to support commercialization of this promising new medicine.",10.1021/acs.oprd.7b00121,2017-08-09,0.6368172206094369
Organic Process Research & Development,"Synthesis and Purification of 6-Ethoxy-4-oxo-1,4-dihydro-[1,5]naphthyridine-3-carboxylic Acid Benzylamide","The synthesis of 6-ethoxy-4-oxo-1,4-dihydro-[1,5]naphthyridine-3-carboxylic acid benzylamide ( 1 ) on multikilogram scale is described. The major challenge for the synthesis of this quinolone GABA partial agonist was in the isolation of product of acceptable purity for clinical studies due to the insolubility of this compound. Also described are efforts to circumvent a high-temperature cyclization required for the synthesis of the quinolone ring system.",10.1021/op0341061,2003-09-30,0.636804601447522
Organic Process Research & Development,Asymmetric Synthesis of <i>iso</i>-Boc (<i>S</i>)-2-Amino-8-nonenoic Acid in One Through-Process,"A practical through-process to prepare iso -Boc ( S )-2-amino-8-nonenoic acid has been developed. The short synthesis utilizes a highly enantioselective, enzymatic reductive amination of an α-keto acid substrate, which is prepared via a Grignard addition to diethyl oxalate. Starting from 7-bromohept-1-ene and without isolation of any intermediates, iso -Boc ( S )-2-amino-8-nonenoic acid is prepared in 60% overall yield and >99.9% ee.",10.1021/acs.oprd.5b00392,2015-12-08,0.6367742733705047
Journal of the American Chemical Society,A Stereocontrolled Synthesis of (+)-Saxitoxin,"A concise stereoselective total synthesis of (+)-saxitoxin is described. A silver(I)-initiated hydroamination cascade constructs the bicyclic guanidinium ion core from a alkynyl bisguanidine. This sequence creates two C-N bonds, one C-O bond, and three rings and forms a single stereoisomer in a single synthetic transformation. This process enabled us to complete the synthesis of (+)-saxitoxin in 14 steps from N-Boc-l-serine methyl ester.",10.1021/ja2098063,2011-11-18,0.6367602508334514
Journal of Organic Chemistry,Antitumor Imidazotetrazines. 35. New Synthetic Routes to the Antitumor Drug Temozolomide,"Three new pathways to the antitumor drug temozolomide (4) have been explored via intermediates 3, 6, and 7. The key intermediate 5-amino-1-(N-methylcarbamoyl)imidazole-4-carboxamide (6) has been successfully converted to 4 in 45% yield by employing sodium nitrite in aqueous tartaric acid at 0-5 degrees C. Compound 6 is prepared from nitrophenyl carbamate 14a and methylamine or directly from 5-aminoimidazole-4-carboxamide (13) and either methyl isocyanate or N-methylcarbamoyl chloride. Temozolomide (4) is also prepared from 8-cyano-3-methylimidazo[5,1-d]-1,2,3,5-tetrazin-4(3H)-one (7) by hydrolysis to the hydrochloride salt of 4 in 10 M hydrochloric acid. Compound 7is prepared from either 5-diazoimidazole-4-carbonitrile (28) and methyl isocyanate or by diazotization of 5-amino-1-(N-methylcarbamoyl)imidazole-4-carbonitrile (25). Attempts to cyclize 5-(3-methyltriazen-1-yl)imidazole-4-carboxamide (3) with phosgene or phosgene equivalents were unsuccessful: only 2-azahypoxanthine (11) was isolated.",10.1021/jo970802l,1997-10-01,0.6367581816905797
Journal of Organic Chemistry,"Synthesis of (−)-Deoxypukalide, the Enantiomer of a Degradation Product of the Furanocembranolide Pukalide","A convergent stereoselective synthesis of (-)-deoxypukalide is described. This substance has not yet been found in Nature but is obtained through deoxygenation of pukalide, the first naturally occurring furanocembrane to be structurally elucidated. The route features a new intraannular furan synthesis that entails treatment of a 4-oxopropargylic beta-keto ester with silica gel. The product of this novel reaction, a 3-carboxy 2,5-bridged furan, is formed in 96% yield. The synthetic strategy was strongly directed by molecular mechanics calculations, which provided valuable insight into stereodefining steps including double bond stereochemistry and butenolide configuration.",10.1021/jo016048s,2001-11-01,0.6367370725943018
Journal of Organic Chemistry,"Synthetic Studies on Dicyclopenta[a,d]cyclooctane Terpenoids: Construction of the Core Structure of Fusicoccins and Ophiobolins on the Route Involving a Wagner-Meerwein Rearrangement","The total diastereoselective synthesis of dicyclopenta[a,d]cyclooctane core skeleton of tricyclic terpenoids, fusicoccins, and ophiobolins is reported. The synthesis commences from 2-methylcyclopent-2-en-1-one and leads first to the easily accessible intermediary cyclopenta[8]annulene 18. The subsequent steps include two key transformations: shifting the angular methyl group from the angular to the neighboring position employing a carbocationic rearrangement (26 → 28) and construction of a quaternary stereogenic center via alkylation of α-methylcyclooctanone intermediate (38 → 48). In the context of the latter transformation, a series of model experiments on alkylation of 2-methylcyclooctan-1-one were conducted. The stereochemical assignments were verified by X-ray analyses of the key structures 39 and 50.",10.1021/jo201357p,2011-08-12,0.6367097200667771
Organic Letters,"Complete Regioselective Addition of Grignard Reagents to Pyrazine <i>N</i>-Oxides, Toward an Efficient Enantioselective Synthesis of Substituted Piperazines","A conceptually new one-pot strategy for the synthesis of protected substituted piperazines via the addition of Grignard reagents to pyrazine N-oxides is presented. This strategy is high yielding (33-91% over three steps), step-efficient, and fast. The synthesized N,N-diprotected piperazines are convenient to handle and allow for orthogonal deprotection at either nitrogen for selective transformations. In addition, this is a synthetic route to enantiomerically enriched piperazines by using a combination of phenyl magnesium chloride and (-)-sparteine, which resulted in enantiomeric excesses up to 83%.",10.1021/ol902619h,2009-12-11,0.6367034523105395
Angewandte Chemie International Edition,"Total Synthesis of Kingianins A, D, and F","A synthesis fit for a king: The total synthesis of (±)-kingianins A, D, and F has been achieved in ten steps. Key features include the gram-scale synthesis and partial reduction of a conjugated tetrayne to a (Z,Z,Z,Z)-tetraene, the domino 8π–6π electrocyclic ring closure of a (Z,Z,Z,Z)-tetraene, and the radical-cation-catalyzed formal Diels–Alder dimerization of functionalized bicyclo[4.2.0]octadiene precursors.",10.1002/anie.201210084,2013-03-06,0.6366975776788111
Journal of Organic Chemistry,Total Synthesis of Natural and Unnatural Lamellarins with Saturated and Unsaturated D-Rings,"Twenty-eight natural and unnatural lamellarins with either a saturated or an unsaturated D-ring were synthesized according to our developed synthetic route. The key step involved the Michael addition/ring closure (Mi-RC) of the benzyldihydroisoquinoline and alpha-nitrocinnamate derivatives, which provided the 2-carboethoxypyrrole intermediates in moderate to good yields (up to 78% yield). Subsequent hydrogenolysis/lactonization furnished lamellarins with a saturated D-ring in excellent yields (up to 93% yield). DDQ oxidation of the saturated lamellarin acetates led directly to the corresponding unsaturated analogues in 54-95% yield. In addition, only two steps in our developed strategy require column chromatography.",10.1021/jo061810h,2006-11-15,0.6366922202950694
Tetrahedron,Enantioselective synthesis of a putative hexaketide intermediate in the biosynthesis of the squalestatins,,10.1016/s0040-4039(97)01174-x,1997-07-01,0.6366846181254989
Organic Process Research & Development,"A Scalable Synthesis of (<i>R</i>)-3,5-Dihydro-4<i>H</i>-dinaphth[2,1-<i>c</i>:1‘2‘-<i>e</i>]azepine","Environmentally benign scalable procedures are developed to supply enantiomerically pure ( R )-3,5-dihydro-4 H -dinaphth[2,1- c:1‘2‘- e ]azepine 1 as its hydrogen oxalate salt in a five-step overall yield of 41%, which consist of the following: (1) bis O -triflation of ( R )-1,1‘-bi-2-naphthol 8 [(CF 3 SO 2 ) 2 O, pyridine, PhMe; quantitative yield]; (2) Kumada's cross-coupling [MeMgI, NiCl 2 (dppp), tert -BuOMe; 96% yield]; (3) radical bromination [ N -bromosuccinimide, 2,2‘-azobisisobutyronitrile, cyclohexane; 54% yield]; (4) cyclization [allylamine, Et 3 N, THF, 86%]; (5) N -deallylation [1,3-dimethylbarbituric acid, Pd(OAc) 2, Ph 3 P, PhMe] followed by crystalline salt formation with oxalic acid (overall 92% yield).",10.1021/op034067t,2003-08-01,0.6366797244705268
Journal of Organic Chemistry,A Practical and Efficient Preparation of the Releasable Naphthosultam Side Chain of a Novel Anti-MRSA Carbapenem,"A practical large-scale synthesis of the naphthosultam-based side chain of the anti-MRSA antibiotic 1 has been achieved in 29% overall yield over seven steps from 1-methylnaphthalene. The synthesis was completed without the use of protecting groups, featuring a novel naphthosultam annelation, a chemoselective acid-catalyzed triflation, and the use of a novel naphthosultam dianion to effect functionalization through benzylic metalation.",10.1021/jo991490k,2000-02-16,0.6366699954395502
Chemical Science,"Efficient syntheses of (−)-crinine and (−)-aspidospermidine, and the formal synthesis of (−)-minfiensine by enantioselective intramolecular dearomative cyclization","-phosphoramide protecting group is essential for the desired chemoselectivity. This method has enabled the enantioselective total syntheses of three distinctive and challenging biologically important polycyclic alkaloids, specifically a concise and gram-scale synthesis of (-)-crinine, an efficient synthesis of indole alkaloid (-)-aspidospermidine and a formal enantioselective synthesis of (-)-minfiensine.",10.1039/c7sc01859b,2017-01-01,0.6366673042470916
Synthesis,Efficient Synthesis of Two Sialylated Tetrasaccharides Found in Goat Milk,Two regioisomeric sialylated tetrasaccharides found in goat milk have been obtained in excellent yield by a concise synthesis using a common disaccharide intermediate. Regioselective glycosylations and a minimal number of protecting-group manipulations are the key features of this synthetic strategy.,10.1055/s-0028-1088032,2009-03-25,0.63666537784012
Organic Letters,A Novel and Efficient Total Synthesis of Cephalotaxine,"[reaction: see text] Total synthesis of cephalotaxine (CET), the parent member of a class of structurally unique antileukemia Cephalotaxus alkaloids, was accomplished on the basis of a conceptually novel strategy featuring transannular reductive skeletal rearrangements as the key transformations for the construction of the pentacyclic ring skeleton of CET. The synthetic potential of the designated Clemmensen-Clemo-Prelog-Leonard reductive rearrangement was demonstrated for the first time in a facile synthesis of the benzazepine subunit of CET. A novel endocyclic enamine (cyclopentenone) annulation was discovered and rationalized as an unusual azo-Nazarov-type cyclization.",10.1021/ol035098b,2003-07-04,0.6366522368645084
Synlett,A New Convergent Approach to Biphenomycin Antibiotics,"A new, convergent approach to the biaryl key intermediate of Schmidt’s biphenomycin B total synthesis has been accomplished via a palladacycle complex catalyzed Stille cross-coupling of two o-tyrosine building blocks.",10.1055/s-2003-37506,2003-01-01,0.6366487879876066
Journal of Organic Chemistry,Total Synthesis of (−)-Normalindine via Addition of Metalated 4-Methyl-3-cyanopyridine to an Enantiopure Sulfinimine,A concise total asymmetric synthesis of the tetrahydronaphthyridine alkaloid (-)-normalindine has been accomplished via the addition of a laterally metalated 4-methyl-3-cyanopyridine to a sulfinimine (N-sulfinyl imine) as the key step.,10.1021/jo061443+,2006-10-18,0.636634190263157
Journal of the American Chemical Society,"Efficient Synthetic Access to the Hetisine C<sub>20</sub>-Diterpenoid Alkaloids. A Concise Synthesis of Nominine via Oxidoisoquinolinium-1,3-Dipolar and Dienamine-Diels−Alder Cycloadditions",A concise synthetic approach to the hetisine C20-diterpenoid alkaloids is reported. The total synthesis of (+/-)-nominine was accomplished in a 15-step sequence employing a dual cycloaddition strategy. Key features of the synthesis include a reversible intramolecular 4-oxidoisoquinolinium betaine dipolar cycloaddition in conjunction with a pyrrolidine-induced dienamine isomerization/Diels-Alder cascade.,10.1021/ja0625430,2006-06-17,0.6366300764348615
Journal of Organic Chemistry,Total Synthesis of (+)-Ansatrienol K,"The first total synthesis of ansatrienol K, a novel trienomycin congener featuring a diene moiety within its 19-membered macrolactam ring, is reported. Key steps include two sequential palladium-catalyzed cross-coupling reactions for constructing the trisubstituted benzene ring and two distinct strategies for assembling the C6–C18 fragment. A Co 2 (CO) 8 -catalyzed carbonylative epoxide ring-opening provided the diene fragment, while late-stage Stewart–Grubbs catalyst-mediated diene-ene ring-closing metathesis (RCM) enabled efficient macrocyclization.",10.1021/acs.joc.5c00383,2025-05-02,0.63662838704385
Journal of Organic Chemistry,"Progress toward the Total Synthesis of Goniodomin A: Stereocontrolled, Convergent Synthesis of the C12–C36 Fragment","Goniodomin A is a marine polyether macrolide natural product isolated from the dinoflagellate Alexandrium hiranoi. In this paper, we report stereocontrolled, convergent synthesis of a fully functionalized C12-C36 fragment of goniodomin A. The synthesis of the C12-C25 vinylstannane involved a Wittig reaction and a reductive cycloetherification for the construction of the dihydropyran ring. The C26-C36 thioester was synthesized via a Nozaki-Hiyama-Kishi reaction of an aldehyde and an iodoalkyne, the former of which was easily prepared from (R)-malic acid as a chiral source by taking advantage of substrate-controlled diastereoselective reactions. Finally, a palladium-catalyzed coupling of the C12-C25 vinylstannane and the C26-C36 thioester completed the synthesis of the target compound.",10.1021/acs.joc.5b02650,2016-01-11,0.636619387722749
Synlett,Asymmetric Synthesis of 4′-Quaternary 2′-Deoxy-3′-<i>epi</i>-β-<i>C</i>-Nucleosides,"An efficient diastereo- and enantioselective synthesis of 4′-quaternary 2′-deoxy-3′-epi-β-C-nucleosides is described employing the RAMP-hydrazone methodology to establish the first stereocentre. Further key steps include diastereoselective nucleophilic 1,2-additions with Grignard and organocerium reagents.",10.1055/s-2005-872658,2005-01-01,0.63660630465329
Organic Letters,Formal Synthesis of <i>Aspidosperma</i> Alkaloids via the Intramolecular [3 + 2] Cycloaddition of 2-Azapentdienyllithiums,"[reaction: see text] A formal synthesis of the Aspidosperma alkaloids aspidospermidine, aspidospermine, and quebrachamine is reported through an efficient preparation of Stork's penultimate intermediate. The key step of the sequence involved an intramolecular [3 + 2] cycloaddition of the 2-azapentadienyllithium 21 formed in situ from the corresponding imine 1, which after N-alkylation of the resulting cycloadduct provided 2 in excellent yield. The synthesis represents a new disconnection of the classical tricyclic ketone used for appendage of the requisite indole.",10.1021/ol0602506,2006-03-22,0.6365984167604373
Synlett,A Concise Route to MK-4482 (EIDD-2801) from Cytidine: Part 2,"Abstract A new route to MK-4482 was developed. The route replaces uridine with the more available and less expensive cytidine. Low-cost, simple reagents are used for the chemical transformations, and the yield is improved from 17% to 44%. A step is removed from the longest linear sequence, and these advancements are expected to expand access to MK-4482 should it become a viable drug substance.",10.1055/a-1275-2848,2020-09-30,0.6365976996120285
Journal of Organic Chemistry,"Total Synthesis of Cryptophycins-1, -3, -4, -24 (Arenastatin A), and -29, Cytotoxic Depsipeptides from Cyanobacteria of the Nostocaceae","A convergent synthesis of cryptophycins has been developed in which (5 S,6 R )-5-hydroxy-6-methyl-8-phenylocta-2( E),7( E) -dienoic acid (A) is coupled with an amino acid segment (B). Two stereoselective routes to A are described, the first employing allylation of an α-homochiral aldehyde and the second using asymmetric crotylation of an achiral aldehyde to establish the two stereogenic centers present in A. The styryl moiety of A was attached either via Stille coupling or through a Wadsworth−Emmons condensation with diethyl benzylphosphonate. The amino acid subunit B was prepared from benzyl (2 S )-2-hydroxyisocaproate by connection first to N -Boc-β-alanine or its (2 R )-methyl-substituted derivative and then to (2 R )- N -Boc- O -methyltyrosine or its m -chloro derivative. Fusion of the A and B subunits was accomplished by initial esterification of the former with the latter, followed by macrocyclization using diphenyl phosphorazidate. In this way, cryptophycin-3, -4, and -29 were obtained along with the nonnatural cyclic depsipeptide 52 . Epoxidation of cryptophycin-3 with dimethyldioxirane gave cryptophycin-1; analogous epoxidation of 52 afforded arenastatin A (cryptophycin-24).",10.1021/jo9907585,1999-08-01,0.6365860747873483
Synthesis,"Concise Synthesis of Coscinamide B, a Bisindolic Enamide from Marine Sponge","An efficient, four-step synthesis of coscinamide B (2) from tryptamine is reported, in which a one-pot benzylic bromination and subsequent in situ dehydrobromination in the absence of an added base is the key step.",10.1055/s-2003-41022,2003-01-01,0.6365796464979774
Organic Process Research & Development,An Enantioselective Hydrogenation of an Alkenoic Acid as a Key Step in the Synthesis of AZD2716,"A classical resolution of a racemic carboxylic acid through salt formation and an asymmetric hydrogenation of an α,β-unsaturated carboxylic acid were investigated in parallel to prepare an enantiomerically pure alkanoic acid used as a key intermediate in the synthesis of an antiplaque candidate drug. After an extensive screening of rhodium- and ruthenium-based catalysts, we developed a rhodium-catalyzed hydrogenation that gave the alkanoic acid with 90% ee, and after a subsequent crystallization with ( R )-1-phenylethanamine, the ee was enriched to 97%. The chiral acid was then used in sequential Negishi and Suzuki couplings followed by basic hydrolysis of a nitrile to an amide to give the active pharmaceutical ingredient in 22% overall yield.",10.1021/acs.oprd.5b00382,2016-01-07,0.6365734728698762
Tetrahedron,Asymmetric synthesis of a novel phenylogous amino acid mimicking an extended dipeptide,,10.1016/0040-4039(95)01877-k,1995-11-01,0.6365699434365709
Organic Letters,Application of Pd(0)-Catalyzed Intramolecular Oxazine Formation to the Efficient Total Synthesis of (−)-Anisomycin,"The enantioselective total synthesis of (-)-anisomycin, a potent antibiotic agent, has been achieved. The key steps are a Pd(0)-catalyzed stereoselective intramolecular oxazine formation from d-tyrosine and pyrrolidine formation by catalytic hydrogenation of the oxazine.",10.1021/ol701519b,2007-08-01,0.6365573430099882
Tetrahedron,Synthetic studies on biscembranoids: asymmetric total synthesis of methyl sarcoate,,10.1016/j.tetlet.2004.12.132,2005-01-15,0.6365495059435468
European Journal of Organic Chemistry,Towards the Total Synthesis of Pamamycin-607: Preparation of the Eastern Part (C8–C18 Fragment),"Pamamycin-607 belongs to a group of homologous macrodiolides, produced by various “Streptomyces”, that possess remarkable autoregulatory antifungal, antibacterial and anion-transfering activities. The synthesis of the non-racemic C8–C18 portion of pamamycin-607 is reported here and involves a route that features a stereoselective aldol condensation followed by a stereocontrolled reductive amination of the aldol and a cis-selective tetrahydrofuran formation by an intramolecular Michael cyclization induced by the geometry of the substrate.",10.1002/(sici)1099-0690(199909)1999:9<2303::aid-ejoc2303>3.0.co;2-8,1999-09-01,0.6365470647470426
Organic Letters,Total Synthesis of Jerangolid A,"The first total synthesis of the antifungal polyketide jerangolid A has been accomplished. Starting with the readily available (R)-Roche ester and (S)-glycidol as chirons, the synthesis involved a highly syn-selective Lewis acid catalyzed 6-endo-trig cyclization for the construction of the dihydropyran subunit. The lactone segment was built through a tandem NaOMe conjugate addition-lactonization reaction, and further functionalized through a sequence consisting of iodination, I-Mg exchange, and hydroxymethylation. Other key steps in the synthesis featured a novel application of a phosphonamide-anion based olefination and a Julia-Kocienski reaction.",10.1021/ol101103q,2010-06-21,0.6365461226404652
Organic Process Research & Development,Direct Construction of Chiral Ether via Highly Efficient Heck Reaction and N-Directed Asymmetric Hydrogenation for Large-Scale Synthesis of MALT1 Inhibitor RGT-068A,"Chemical process development efforts leading to the large-scale production of RGT-068A are discussed. Process optimization resulted in (1) successful replacement of the Stille coupling reaction involving toxic stannane reagent via highly efficient Heck reaction of methyl vinyl ether, (2) construction of the chiral ether unit through N-directed Ru-catalyzed asymmetric hydrogenation avoiding super-critical fluid chromatography (SFC) chiral separation, and (3) a streamlined process with a significantly improved overall yield of about 25%, 5-fold higher than the original discovery synthetic route, which enabled the delivery of high-quality material for IND-enabling studies.",10.1021/acs.oprd.2c00229,2022-11-03,0.6365394404720283
Angewandte Chemie International Edition,Enantioselective Total Syntheses of Manginoids A and C and Guignardones A and C,"An enantioselective synthetic approach for preparing manginoids and guignardones, two types of biogenetically related meroterpenoids, is reported. This bioinspired and divergent synthesis employs an oxidative 1,3-dicarbonyl radical-initiated cyclization and cyclodehydration of the common precursor to forge the central ring of the manginoids and guignardones, respectively, at a late stage. Key synthetic steps include silica-gel-promoted semipinacol rearrangement to form the 6-oxabicyclo[3.2.1]octane skeleton and the Suzuki-Miyaura reaction of vinyl bromide to achieve fragment coupling. This synthesis protocol enables the asymmetric syntheses of four fungal meroterpenoids from commercially available materials.",10.1002/anie.202104182,2021-04-20,0.6365328838017831
Tetrahedron,Synthesis of a ring-scission analogue of neplanocin A as a potential inhibitor of S-adenosylhomocysteine hydrolase,,10.1016/0040-4039(93)88109-v,1993-10-01,0.636531400041507
Journal of the American Chemical Society,Total Synthesis of Ecteinascidin 743,A convergent total synthesis of ecteinascidin 743 is realized from five building blocks of almost equal size. It takes 23 steps from l-3-hydroxy-4-methoxy-5-methyl phenylalanol (5) with an overall yield of 3%.,10.1021/ja0571794,2005-12-07,0.636516267520182
Organic Letters,Improved Synthesis of Epothilone B Employing Alkylation of an Alkyne for Assembly of Subunits,"[formula: see text] A strategy for assembling the two principal modules of epothilone B was developed that merges an allylic bromide with a terminal acetylene to fabricate the C10-C11 bond of the macrocycle. The resulting alkyne was semihydrogenated to give a seco ester previously employed in our total synthesis of epothilone B. This new approach affords a more efficient route to the naturally occurring macrolide and to its 9,10-dehydro analogue.",10.1021/ol990248x,1999-10-07,0.6364917118491416
Tetrahedron,Efficient synthesis of the siderophore petrobactin via antimony triethoxide mediated coupling,,10.1016/j.tetlet.2012.01.074,2012-01-30,0.6364807741109445
Journal of Organic Chemistry,Synthesis of 4-Deacetyl-1-dimethylsilyl-7-triethylsilylbaccatin III,"A one-pot trisilylation step to protect three hydroxyl groups of baccatin III (1), followed by hydride ester cleavage and base hydrolysis of a triethylsilyl ether at C13, provides efficient access to a key intermediate 9 (top path). This route removes two steps from a previously established reaction sequence to 9 (bottom path). In principle, inclusion of the truncated reaction sequence into widely utilized semisynthetic routes to next generation Taxol (paclitaxel) compounds could conceivably shorten the overall process.",10.1021/jo802598m,2009-01-29,0.6364654469403429
Organic Process Research & Development,Development of a Robust and Scalable Process for the Large-Scale Preparation of Vilazodone,"A robust and scalable synthesis for vilazodone was developed to avoid the formation of impurities derived from N-detosylation reactions under alcoholic conditions. During our research, these impurities, potentially genotoxic alkyl tosylate and out-of-specification indole N-alkylated vilazodones, were identified as process impurities that have never been reported. Through adjusting the functionality transformations, this process successfully prevented the tosyl group from encountering any alkoxides, which would inevitably lead to the generation of alkyl tosylate and indole N-alkylated vilazodone byproducts. In addition, this manufacturing process has also been demonstrated on a kilogram scale, delivering 1.05 kg of vilazodone hydrochloride with an overall yield of 71% (calculated from ethyl 5-(piperazin-1-yl)benzofuran-2-carboxylate hydrochloride 7·HCl ). HPLC purity of the product was detected >99.5%, with any single impurity <0.1% HPLC area percentage. Indole N-alkylated vilazodones were not detected, and the yield was 10% higher than the previous Friedel–Crafts acylation route.",10.1021/acs.oprd.2c00206,2022-09-29,0.6364610553756993
European Journal of Organic Chemistry,"Facile Synthesis of Tumor‐Associated Carbohydrate Antigen Ganglioside GM<sub>3</sub> from Sialic Acid, Lactose, and Serine","Abstract Ganglioside GM 3 [α‐Neu5Ac‐(2,3)‐β‐Gal‐(1,4)‐β‐Glc‐(1,1)‐Cer; 1 ] is considered as an important tumor‐associated carbohydrate antigen, which can be used in the development of tumor vaccine. In this study, a facile and convergent synthetic strategy for GM 3 was developed, and the preparation of three building blocks started from the most readily available compounds sialic acid, lactose, and L ‐serine. Ceramide aglycon 9 was constructed from L ‐serine in 13 steps with 6 % overall yield, and lactosyl trichloroacetimidate 14 was synthesized from lactose in 7 steps with 25 % yield. With novel N ‐acetyl‐5‐ N ,4‐ O ‐oxazolidinone protected p ‐toluenethiosialoside 15 as donor, which was developed by our group, the sialylation of benzoyl‐protected lactosyl ceramide diol 23 was successfully accomplished in 54 % yield. Our strategy here provides a shorter linear total synthesis of GM 3 in five steps and with 26 % overall yield. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2009)",10.1002/ejoc.200900778,2009-10-13,0.6364590880658633
Organic Letters,Synthesis of Antimitotic Analogs of the Microtubule Stabilizing Sponge Alkaloid Ceratamine A,"Antimitotic analogs of the microtubule stabilizing sponge alkaloid ceratamine A (1) have been synthesized starting from tribromoimidazole. A key step in the synthesis is the formation of the azepine ring via an intramolecular Buchwald coupling between a vinyl bromide and a N-methyl amide. This represents the first synthesis of a fully unsaturated imidazo[4,5,d]azepine. NMR data obtained for the synthetic ceratamine analogs has provided support for the structure assigned to the natural product.",10.1021/ol7030284,2008-02-16,0.6364331995744019
Journal of Organic Chemistry,A convergent total synthesis of methoxatin,"We report a convergent total synthesis of the coenzyme methoxatin (1) by linking a pyrrole subunit with an uvitonic acid derivative and oxidative photocyclization to a deoxymethoxatin triester, followed by seven refunctionalization steps to 1.",10.1021/jo00345a057,1982-03-01,0.6364281886129354
Journal of Organic Chemistry,Synthetic Efforts toward the Macrolactone Core of Leucascandrolide A,"A chemoselective synthesis of 1, the macrocyclic core of leucascandrolide A, has been achieved by utilizing highly enantioselective allylmetalations, an enantioselective Noyori reduction of a propargylic ketone, and olefin metatheses as the key steps.",10.1021/jo701315h,2008-01-30,0.6364045599369597
Organic Letters,Total Synthesis of Cochleamycin A,"[reaction: see text] Cochleamycin A (1) was synthesized in 2.4% overall yield via a 23-step linear sequence starting from 3-butene-1-ol. Key features of the synthesis include the synthesis of (Z)-1,3-diene 21 via a Stille coupling of 4 and 5 and a transannular Diels-Alder reaction of macrocycle 26 to provide the complete carbon skeleton of 1.",10.1021/ol049331x,2004-05-13,0.6364011676696412
Journal of Organic Chemistry,Nickel-Catalyzed Synthesis of Benzocoumarins:  Application to the Total Synthesis of Arnottin I,"The ring-opening addition of methyl 2,3-dimethoxy-6-iodobenzoate to oxabenzonorbornadienes followed by cyclization in the presence of NiBr2(dppe) and Zn metal powder in acetonitrile at 80 degrees C to give the corresponding benzocoumarin derivatives is described. This methodology was then applied to the synthesis of natural product arnottin I, first isolated from Xanthoxylum arnottianum Maxim, using protecting group chemistry. After deprotection and subsequent ring closure, arnottin I was obtained in 21% overall yield after six steps starting from catechol.",10.1021/jo061477h,2006-09-13,0.6363866758157772
Tetrahedron,Highly efficient synthesis of alkylidene- and allylidenecyclopropanes,,10.1016/0040-4039(88)80006-6,1988-01-01,0.6363840893912638
Tetrahedron,"A highly-efficient synthesis of benzoxazine-2,4-diones",,10.1016/s0040-4039(98)00223-8,1998-04-01,0.6363840893912638
Tetrahedron,A highly stereocontrolled and efficient synthesis of α- and β-pseudouridines,,10.1016/j.tetlet.2003.09.103,2003-10-15,0.6363840893912638
Tetrahedron,A highly efficient synthesis of unnatural l-sugars from d-ribose,,10.1016/j.tetlet.2005.06.117,2005-07-12,0.6363840893912638
Tetrahedron,"An efficient and highly flexible synthesis of (α),β-unsaturated γ-oxoesters",,10.1016/s0040-4039(00)87247-0,1982-01-01,0.6363840893912638
Journal of the American Chemical Society,A triply convergent total synthesis of l(-)-prostaglandin E2,"This dissertation describes an efficient and versatile total synthesis of l-(-)-prostaglandin E(,2) (PGE(,2)). PGE(,2) was chosen as the target molecule since synthetic procedures have already been developed for transformation of PGE(,2) into most of the other prostaglandins as well as the very important prostacyclin (PGI(,2)). The synthesis features a general triply-convergent step in which the basic prostaglandin skeleton is formed via 1,4-addition of a chiral vinyllithium reagent to a chiral aminovinyl sulfone followed by subsequent in situ alkylation of the resulting sulfone-stabilized anion. Desulfonylation followed by oxidation produces epoxy-prostaglandins which result from a novel epoxidation reaction of an intermediate (alpha),(beta)-unsaturated iminium ion. The synthesis of PGE(,2) from the key intermediate makes use of an efficient peracetic acid oxidation of a secondary amine to a (beta)-siloxy oxime which is in turn desulfonylated by a unique 1,4-elimination of phenylsulfinic acid to generate an intermediate vinyl nitroso species which undergoes stereospecific 1,4-reduction by sodium borohydride to yield the oxime of PGE(,2). This oxime is hydrolyzed using paraformaldehyde and boron trifluoride catalyst to give PGE(,2) in high yield. The synthesis also features an efficient enantioconvergent process for the synthesis of the requisite chiral aminovinyl sulfone acceptor. This process utilizes stereospecific S(,N)2' reactions and a stereospecific sulfide-directed epoxidation sequence. Appendix A describes a high yield generation of 1,4-dihydroaryl silyl ethers through lithium in ammonia reduction of the corresponding tert-butyldimethyl and isopropyldimethylsilyl aryl ethers. The silyl enol ethers produced may be regiospecifically functionalized to nonconjugated (beta),(gamma)-unsaturated ketones.",10.1021/ja00398a048,1981-04-01,0.6363815954444653
Organic Letters,Total Synthesis of LFA-1 Antagonist BIRT-377 via Organocatalytic Asymmetric Construction of a Quaternary Stereocenter,"A catalytic route for enantioselective total synthesis of cell adhesion inhibitor BIRT-377 is described. The quaternary stereocenter was constructed through l-proline-derived, tetrazole-catalyzed direct asymmetric alpha-amination of 3-(4-bromophenyl)-2-methylpropanal with dibenzyl azodicarboxylate. In the course of these studies, a one-pot trifluoro acetylation/selective benzyloxycarbonyl deprotection method was developed. [structure: see text]",10.1021/ol047368b,2005-01-28,0.6363616965755287
Synthesis,Practical Synthesis of ε-Carotene,"A novel route for the total synthesis of ε-carotene is described. The synthesis is based on a condensation between α-cyclocitral and diethyl [(2 E )-3-methoxy-2-methylprop-2-en-1-yl]phosphonate to give a C 14 enol ether, hydrolysis of the C 14 -enol ether to a give a C 14 aldehyde, and a modified Wittig–Horner reaction of the C 15 phosphonate from the C 14 aldehyde and a C 10 triene dialdehyde to give ε-carotene. The synthetic steps are easily performed and are practical for large-scale production.",10.1055/s-0034-1378941,2014-12-05,0.6363615493003303
Synthesis,Stereoselective Total Synthesis of Arundinolides A and B,"The efficient and enantioselective syntheses of arundinolides A and B have been accomplished for the first time from chiral pool methyl-2,3-O-isopropylidene-β-d-ribofuranoside and d-ethyl lactate. The key features of the total synthesis are intramolecular crotonyl migration and NaBH4-CuCl catalyzed regioselective reduction and cross-metathesis reaction.",10.1055/s-0039-1691699,2020-02-05,0.6363493113174032
Tetrahedron,"An efficient synthetic-route to prepare [2,3,6-tri-O-(2-bromo-2-methylpropionyl]-β-cyclodextrin)",,10.1016/j.tetlet.2005.02.027,2005-02-21,0.6363429797185439
European Journal of Organic Chemistry,Chemo-Enzymatic Synthesis of Thymidine13C-Labelled in the 2′-Deoxyribose Moiety,"A synthesis of [3′,4′-13C2]thymidine (1) is described in which [13C2]acetic acid (2) is converted into the nucleoside in twelve steps with 9% overall yield. D-2-Deoxyribose-5-phosphate aldolase (DERA, EC 4.1.2.4) and triosephosphate isomerase (TPI, EC 5.3.1.1) are used for the stereocontrolled formation of D-[3,4-13C2]-2-deoxyribose-5-phosphate (8) from [2,3-13C2]dihydroxyacetone monophosphate (DHAP, 7) and acetaldehyde in 80% yield. The route permits the introduction of isotopically enriched carbon atoms at any position or combination of positions in the furanose ring and the product can be coupled with any of the four naturally occurring base moieties.",10.1002/(sici)1099-0690(200003)2000:5<861::aid-ejoc861>3.0.co;2-e,2000-03-01,0.6363226153114104
Synlett,Novel Three-Step Synthesis of (±)-Harmicine,All articles of this category (opens in new window),10.1055/s-2004-830856,2004-01-01,0.6363188971668859
Organic Letters,Synthesis of EFdA via a Diastereoselective Aldol Reaction of a Protected 3-Keto Furanose,"An efficient enantioselective total synthesis of EFdA, a remarkably potent anti-HIV nucleoside analogue with various favorable pharmacological profiles, has been achieved in 37% overall yield from diacetone-D-glucose by a 14-step sequence that features a highly diastereoselective installation of the tetrasubstituted stereogenic center at the C4' position, direct oxidative cleavage of an acetonide-protected diol derivative to an aldehyde, and one-pot 2'-deoxygenation of a ribonucleoside intermediate.",10.1021/ol5036535,2015-02-02,0.6363142737694285
Organic Process Research & Development,"An Efficient and Scalable Synthesis of <i>tert</i>-Butyl (3a<i>R</i>,6a<i>S</i>)-5-Oxohexahydrocyclo penta[<i>c</i>]pyrrole-2(1<i>H</i>)-carboxylate: A Pharmacologically Important Intermediate","Hexahydrocyclopentapyrrolone derivatives constitute an important class of bicycles, and it represents an essential pharmacophore for diversified pharmacological activities. A highly efficient process for the synthesis of tert -butyl(3a R,6a S )-5-oxohexahydrocyclopenta[ c ]pyrrole-2(1 H )-carboxylate 1 has been developed. The improved process involves transformation of isoindole 4 to diacid 5, using an inexpensive KMnO 4 mediated oxidative cleavage as a key step. The developed process was cost-effective, high yielding, kilogram scalable, and commercially viable for synthesis of 1 .",10.1021/acs.oprd.6b00399,2017-01-23,0.6362708901502854
Organic Letters,Scalable Synthesis of Silacyclohexanones and Ready Access to Silicon Building Blocks,"A simple and efficient two-step method for the synthesis of silacyclohexanones starting from bis (bromoethylsilanes) using TosMIC is presented. The prepared silacyclohexanones were transformed to nine different heterocycles with silicon incorporation. In addition, the developed methodology was used for the synthesis of a sila analogue of the HDAC6 inhibitor tubastatin A.",10.1021/acs.orglett.3c02561,2023-09-08,0.6362702675536935
Organic Letters,Progress toward the Total Synthesis of Ciguatoxins:  A Convergent Synthesis of the FGHIJKLM Ring Fragment,"[structure: see text] A highly convergent synthetic route to the FGHIJKLM ring fragment of ciguatoxins has been developed, which relied on extensive use of the B-alkyl Suzuki-Miyaura coupling reaction.",10.1021/ol026306n,2002-07-16,0.6362616962920358
Organic Letters,Enantioselective Total Synthesis and Absolute Configuration Assignment of (+)-Toxicodenane A,"We present the first enantioselective total synthesis and absolute configuration assignment of (+)-toxicodenane A via a nine-step sequence from the readily available material. The synthesis features a desymmetric enantioselective reduction of 2,2-disubstituted 1,3-cyclohexanedione for the synthesis of a chiral 2,2-disubstituted 3-hydroxy cyclohexanone building block, a highly diastereoselective Grignard reaction for the incorporation of an allyl group, and a Lewis acid-mediated intramolecular transacetalation and Prins cascade reaction for the construction of oxa-bridged bicyclic rings.",10.1021/acs.orglett.1c03293,2021-10-15,0.6362509702919807
Organic Process Research & Development,"Route Optimization of the Noncovalent Modulator of Hemoglobin PF-07059013 for Treatment of Sickle Cell Disease through a Palladium-Mediated C–O Coupling, Part II: Pilot Plant Scale Manufacture","Herein, we report the optimization of the first process chemistry route for pilot-plant-scale manufacture of PF-07059013 ( 1 ), a noncovalent modulator of hemoglobin for the treatment of sickle cell disease. Five areas of improvement are discussed in detail, namely, an alternative synthetic sequence to install the pyridone functionality before benzylic ether formation, a shorter and safer route to quinoline fragment 9, a tosyl-swap strategy to avoid isolation of a thermally unstable tosylate intermediate, Pd-catalyzed C–O coupling with low catalyst loading and efficient Pd removal, and improved final isolation of the API freebase. The new route was executed in our pilot plant facility to deliver 76 kg of API.",10.1021/acs.oprd.3c00038,2023-05-04,0.6362404539335044
Tetrahedron,Development of a convenient route for the preparation of the N2-Cbz-protected guaninyl synthon required for Boc-mediated PNA synthesis,,10.1016/j.tetlet.2013.09.034,2013-09-18,0.6362381405144679
Journal of Organic Chemistry,An Efficient Two-Step Total Synthesis of the Quaterpyridine Nemertelline,"Regioselective and univocal Suzuki cross-coupling reactions performed on halopyridinyl boronic acids provide a flexible and versatile route to a multigram scale synthesis of 2,2'-dichloro-3,4'-bipyridine 14, which allows couplings with excess pyridin-3-yl boronic acid to give a new and efficient two-step rapid synthesis of nemertelline, the quaterpyridine neurotoxin isolated from a Hoplonemertine sea worm.",10.1021/jo034805b,2003-11-25,0.6362363877720092
Angewandte Chemie International Edition,Total Synthesis of Cavicularin and Riccardin C: Addressing the Synthesis of an Arene That Adopts a Boat Configuration,"A transannular ring contraction induced by the addition of an aryl radical intermediate to a proximal arene facilitated the construction of the highly strained macrocyclic core of cavicularin (1). The precursor, an iodinated derivative of another natural product, riccardin C, was prepared from four commercially available arenes in a highly convergent sequence.",10.1002/anie.200500466,2005-05-18,0.6362321652944868
Synlett,Stereoselective Synthesis of the C(53)-C(67) Polyene Fragment of Amphidinol 3,"A stereoselective synthesis of the polyene fragment C(53)-C(67) of amphidinol 3 is described using a sequence of reduction, benzoylation, and reductive elimination for the stereospecific preparation of the polyene motif as key steps starting from acetylenic precursors.",10.1055/s-2007-985601,2007-09-01,0.6362261479163641
Organic Letters,Total Synthesis of (±)-Cochlearol A,"Total synthesis of (±)-cochlearol A was accomplished, which features a cis 6/6 B/D ring synthesis. A TMSOTf-promoted lactonization of tert -butoxy ketoester produced the desired lactone with quaternary carbon. The cis configuration of the B/E ring is essential for regioselective B/D ring formation. Finally, simple deprotections and transformations gave cochlearol A in 16 steps from known ethyl 4- tert -butoxyacetoacetate.",10.1021/acs.orglett.9b02391,2019-08-21,0.6362224762219452
Journal of Organic Chemistry,"A New Enantiospecific Synthesis of α-Santalanes via Homofragmentation of 1,4-Diol Monosulfonate Esters","The homofragmentation of 1,4-diol monosulfonate esters was applied as a key step in the synthesis of α-santalanes. The enantiospecific synthesis of (+)-α-santalan-12-one ( 1d ) was achieved via the tricyclic dione 2 as an intermediate that could be obtained from ( R )-(−)-carvone. A 1,2-carbonyl transposition in dione 2 followed by functional group transformations afforded the tricyclic 1,4-diol monomesylate 3, which could be homofragmented in 76% yield to the tricyclic aldehyde 4 . From this compound the synthesis of several α-santalanes can be achieved; the synthesis of 1d was accomplished in 11 steps from 2 in 8% overall yield.",10.1021/jo9603892,1996-01-01,0.6362155657640506
Synlett,"A Concise Approach to the 5-Oxo-6,7-Dihydrofuranopyrone Skeleton","An efficient, stereoselective route to the 3-acetoxy-5-oxo-6,7-dihydrofuranopyrone skeleton from furan is described. The key steps in this approach include enzymatic desymmetrization of the meso-diol 5a and ROM-CM-RCM sequence achieved on a conveniently substituted derivative 3.",10.1055/s-2006-933143,2006-03-14,0.6362140435767115
Angewandte Chemie International Edition,Arylnaphthalene Lignans through Pd‐Catalyzed [2+2+2] Cocyclization of Arynes and Diynes: Total Synthesis of Taiwanins C and E,"3 in 1: A novel method for the synthesis of the arylnaphthalene skeleton by the Pd0-catalyzed [2+2+2] cocyclization of diynes and arynes involves three CC bond-forming reactions in a single step (see scheme; R=CON(OCH3)CH3, dba=dibenzylideneacetone). This cocyclization was the key step in the total synthesis of the arylnaphthalene lignans taiwanins C and E.",10.1002/anie.200453809,2004-04-22,0.6362107872265391
Tetrahedron,"Unexpected intramolecular nucleophilic cyclization of ureidoacetamide: A novel route towards the synthesis of 2,4,5-trisubsituted oxazoles",,10.1016/j.tetlet.2019.05.028,2019-05-15,0.6362084041619005
Journal of Organic Chemistry,Total Synthesis of Plusbacin A<sub>3</sub> and Its Dideoxy Derivative Using a Solvent-Dependent Diastereodivergent Joullié–Ugi Three-Component Reaction,"(1), which is a depsipeptide with antibacterial activity, and its dideoxy derivative are described. To establish an efficient synthetic route of 1, a solvent-dependent diastereodivergent Joullié-Ugi three-component reaction (JU-3CR) was used to construct trans-Pro(3-OH) in a small number of steps. Two strategies were investigated toward the total synthesis. In the first synthetic strategy, the key steps were the trans-selective JU-3CR and a macrolactonization at the final stage of the synthesis. The JU-3CR using alkyl isocyanides in 1,1,1,3,3,3-hexafluoroisopropanol provided the trans products, and the coupling of the fragments to prepare the macrocyclization precursor proceeded smoothly. However, attempts toward the macrolactonization did not provide the desired product. Then, the second strategy that included esterification in an initial stage was investigated. Methods for constructing trans-Pro(3-OH) were examined using a convertible isocyanide, which could be converted to a carboxylic acid required for the following amidation. Ester bond formation was achieved through an intermolecular coupling using a hydroxyl-Asp derivative and the corresponding alcohol, and the amidation afforded a linear depsipeptide. The macrolactamization of the linear peptide gave the cyclic depsipeptide, and then the global deprotection accomplished the total synthesis of 1 and its dideoxy derivative.",10.1021/acs.joc.8b00038,2018-02-19,0.6362066389263117
Organic Letters,"A Two-Step Total Synthesis of the Natural Pentacycle Trichodimerol, a Novel Inhibitor of TNF-α Production",[formula: see text] Trichodimerol (1) can be synthesized by a remarkable dimerization of the chiral hydroxy dienone 5.,10.1021/ol991070h,1999-09-30,0.6362059873146962
Organic Process Research & Development,Route Development toward a Pyrazine Building Block to Enable Early Scale-Up Campaigns,"We required rapid access to hundreds of grams of a key building block to support early scale-up campaigns during one of our Oncology programs. Accordingly, we report herein the exploration of two synthetic approaches to this compound by our Discovery Process team. This work culminated in the development and optimization of a phase-appropriate synthetic route that was successfully utilized by one of our contract development and manufacturing organizations (CDMOs) to quickly deliver 300 g of intermediate 1•TsOH .",10.1021/acs.oprd.5c00280,2025-11-03,0.6362000221427474
Organic Letters,Synthesis of the Bioherbicidal Fungus Metabolite Macrocidin A,"The second total synthesis of macrocidin A afforded the bioherbicidal fungal metabolite in 16 steps starting from doubly protected l-tyrosine. The 3-octanoyl side chain with the α-methyl group and an ω-bromo epoxide already in place was attached to the tetramic acid via a Yoshii-Yoda acylation, and the macrocycle was eventually closed in 55% yield by a Williamson etherification between the phenolate and the epoxy bromide.",10.1021/acs.orglett.6b03240,2016-11-28,0.6361903470764663
Journal of Organic Chemistry,"Total Synthesis of Tiacumicin A. Total Synthesis, Relay Synthesis, and Degradation Studies of Fidaxomicin (Tiacumicin B, Lipiarmycin A3)","The commercial macrolide antibiotic fidaxomicin was synthesized in a highly convergent manner. Salient features of this synthesis include a β-selective noviosylation, a β-selective rhamnosylation, a ring-closing metathesis, a Suzuki coupling, and a vinylogous Mukaiyama aldol reaction. Careful choice of protecting groups and fine-tuning of the glycosylation reactions led to the first total synthesis of fidaxomicin. In addition, a relay synthesis of fidaxomicin was established, which gives access to a conveniently protected intermediate from the natural material for derivatization. The first total synthesis of a related congener, tiacumicin A, is presented.",10.1021/acs.joc.8b00101,2018-03-29,0.6361723059528119
Tetrahedron,Synthesis of a new tricyclic 3-(tetrazol-5-yl)pyridine system from 2-(azidomethyl)nicotinonitriles,,10.1016/j.tetlet.2004.10.016,2004-11-01,0.6361649818926868
Synlett,"Scalable Synthesis of 2,2′-Anhydro-arabinofuranosyl Imidazoles","We report the efficient and scalable synthesis of 2,2′-anhydro-5-amino-1-β-arabinofuranosylimidazole-4-carboxamide and 2,2′-anhydro-5-amino-1-β-arabinofuranosylimidazole-4-carbonitrile from commercial arabino-adenosine. 2,2′-Anhydro-5-amino-1-β-arabinofuranosylimidazole-4-carboxamide is synthesised in only five steps with a single chromatographic purification. Additionally, we report a high-yielding, three-step conversion of 2,2′-anhydro-5-amino-1-β-arabinofuranosylimidazole-4-carboxamide into 2,2′-anhydro-5-amino-1-β-arabinofuranosylimidazole-4-carbonitrile. They are proposed key intermediates of the divergent prebiotic synthesis of ribonucleotides and this facile synthesis is anticipated to be instrumental in continued investigation of the origins of nucleotides.",10.1055/s-0036-1590968,2017-07-27,0.6361604995101302
Synthesis,Asymmetric Synthesis of cis-5-(Aminomethyl)-3-(4-methoxyphenyl)dihydrofuran-2(3H)-one,"The asymmetric synthesis of (3R,5S)-5-(aminomethyl)-3-(4-methoxyphenyl)dihydrofuran-2(3H)-one, as the most potent selective inactivator of monoamine B, was successfully achieved by applying a newly developed synthetic method toward the key γ-aminomethyl-γ-lactone via intramolecular aziridine ring opening in 63% overall yield from a commercial starting material.",10.1055/s-0037-1610667,2018-11-08,0.63615086969155
Tetrahedron,Efficient total synthesis of (+)-curcuphenol via asymmetric organocatalysis,,10.1016/j.tetlet.2005.02.047,2005-02-24,0.6361455987006388
Synlett,Synthesis of the Tricyclic Core of the Marine Alkaloid Lepadiformine,"A stereoselective synthesis of the tricyclic core in ra­cemic form of the marine alkaloid Lepadiformine is described from 4-methoxy-3-pyrrolin-2-one (methyl tetramate). Key steps involve 5,5-dialkylation of the tetramate, metathesis closure to an A/C 1-azaspirocycle and stereoselective hydrogenation for the trans A/B 1-azadecalin system.",10.1055/s-2003-36782,2003-01-01,0.6361425125390635
Organic Letters,Synthesis of the C1–C11 Western Fragment of Madeirolide A,"The stereocontrolled synthesis of a fully elaborated C1-11 subunit of madeirolide A is described, utilizing an asymmetric boron aldol reaction and a cis-selective hetero-Michael cyclization to form the tetrahydropyran ring, followed by efficient formation of the required C5 α-glycoside.",10.1021/ol400280b,2013-03-01,0.6361424531635991
Journal of Organic Chemistry,Asymmetric Total Synthesis of Amphirionin-2,"A convergent route for the asymmetric total synthesis of potent anticancer polyketide natural product amphirionin-2 has been developed. Our initial synthetic trials revealed that the proposed structures of amphirionin-2 need to be revised consistent with a recent report of Fuwa et al., where the actual structure of amphirionin-2 was established. The key features of our synthesis comprised Sharpless asymmetric dihydroxylation, followed by cycloetherification, Wittig olefination, Julia-Kocienski olefination, and Crimmins propionate aldol reaction.",10.1021/acs.joc.1c00686,2021-07-16,0.6361278479907126
Angewandte Chemie International Edition,A Short Synthesis of (±)‐3‐Demethoxyerythratidinone by Ligand‐Controlled Selective Heck Cyclization of Equilibrating Enamines,"A short, 5-step total synthesis of (±)-3-demethoxyerythratidinone from a simple pyrrole derivative is described. Features include the formation of gram quantities of a key tricylic aziridine from a challenging photochemical cascade reaction through the use of flow photochemistry. The final step involved a highly unusual Heck cyclization whereby ligand control enabled efficient formation of the natural product in 69 % yield from the minor isomer present in an equilibrating mixture of labile enamines.",10.1002/anie.201701775,2017-05-04,0.6361151536958033
Angewandte Chemie International Edition,Total Synthesis of the Bacterial RNA Polymerase Inhibitor Ripostatin B,A modular and highly stereoselective synthesis of the title compound was developed. Key steps in the assembly of the carbon framework of ripostatin B were a stereoselective Paterson aldol reaction and a high-yielding ring-closing metathesis mediated by Grubbs first generation catalyst. The C15 hydroxy group was established through Tishchenko-Evans reduction in excellent yield and selectivity.,10.1002/anie.201200871,2012-02-29,0.6360968792582774
Organic Letters,Enantioselective Formal Synthesis of Palmerolide A,"Enantioselective formal synthesis of macrolactone palmerolide A, a polyketide marine natural product, is described. Key strategies in the synthesis include the oxidative furan ring-opening of a chiral furyl carbinol for the installation of the 1,4-dienol core and a Jung nonaldol-aldol reaction for the dienamide core.",10.1021/ol201604c,2011-07-27,0.6360909324333466
Tetrahedron,"The first total synthesis of hibarimicinone, a potent v-Src tyrosine kinase inhibitor",,10.1016/j.tetlet.2011.11.062,2011-11-22,0.6360853453671156
Organic Letters,Total Synthesis of the Marine Alkaloid (−)-Lepadin B,"An enantioselective total synthesis of (-)-lepadin B has been developed starting from (2S,4S)-2,4-O-benzylidene-2, 4-dihydroxybutanal. The key steps in the synthesis include the use of an aqueous intramolecular acylnitroso Diels-Alder reaction to afford the trans-1,2-oxazinolactam and Suzuki cross-coupling reaction to elaborate the (E,E)-octadienyl unit.",10.1021/ol000153r,2000-08-25,0.6360852325198233
Journal of Organic Chemistry,Total Synthesis of Microtubule-Stabilizing Agent (−)-Laulimalide<sup>1</sup>,"An enantioselective first total synthesis of laulimalide (1) is described. Laulimalide, a remarkably potent antitumor macrolide, has been isolated from the Indonesian sponge Hyattella sp. and the Okinawan sponge Fasciospongia rimosa. Laulimalide represents a new class of antitumor agents with significant clinical potential. The synthesis is convergent and involved the assembly of C(3)-C(16) segment 4 and C(17)-C(28) segment 5 by Julia olefination. The sensitive C(2)-C(3) cis-olefin functionality was installed by Yamaguchi macrolactonization of a hydroxy alkynic acid followed by hydrogenation of the resulting alkynoic lactone over Lindlar's catalyst. Initial attempts of intramolecular Still's variant of Horner-Emmons olefination between the C(19)-phosphonocetate and C(3)-aldehyde provided a 1:2 mixture of cis- and trans-macrolactones. The trans-isomer was photoisomerized to a mixture of cis- and trans-isomers. The other key steps involved ring-closing olefin metathesis to construct both dihydropyran units, stereoselective anomeric alkylation to functionalize the dihydropyran ring, stereoselective reduction of the resulting alkynyl ketone to set the C(20)-hydroxyl stereochemistry, and a novel Julia olefination protocol for the installation of the C(13)-exo-methylene unit. The sensitive epoxide at C(16)-C(17) was introduced in a highly stereoselective manner by Sharpless epoxidation at the final stage of the synthesis.",10.1021/jo010854h,2001-11-30,0.6360753164869696
Journal of Organic Chemistry,"Total Synthesis of Caldorazole, a Potent Mitochondrial Respiratory Chain Inhibitor without Chiral Centers",") is a novel polyketide that was isolated from a marine cyanobacterium in 2022. It is a unique natural product that exhibits potent inhibitory activity against mitochondrial respiratory chain complex I despite having no chiral centers. To establish a method for obtaining caldorazole without relying on biological resources and for constructing a useful synthetic route for studies of its structure-activity relationship, we achieved the first total synthesis of caldorazole using a convergent synthetic route.",10.1021/acs.joc.2c03007,2023-02-17,0.6360695826614549
Tetrahedron,A route to the synthesis of previously unknown α-heteroatom substituted nitrones,,10.1016/s0040-4039(02)00279-4,2002-03-01,0.6360541400680446
Tetrahedron,"Preparation of methyl-2-(ω-iodoalkyl)propenoates and a facile route to 2-carbomethoxy-1,3-butadiene",,10.1016/s0040-4039(01)93823-7,1989-01-01,0.6360537139770203
Organic Letters,Asymmetric Total Synthesis of (+)-Quinocarcinamide,"The first asymmetric total synthesis of (+)-quinocarcinamide ( 3 ), an enantiomer of the natural oxidation product from antitumor antibiotic (−)-quinocarcin ( 1 ), is described. Key steps include an iridium-catalyzed asymmetric allylic amidation of racemic alcohol 9, olefin cross-metathesis followed by a S N 2′ to forge tetrahydroisoquinoline, and stereocontrolled 1,3-dipolar cycloaddition between a facilely generated azomethine ylide and tert -butyl acrylate to construct the diazabicyclo[3.2.1]octane ring.",10.1021/acs.orglett.1c02970,2021-09-29,0.6360440692096766
Organic Process Research & Development,Process Development of Citalopram/Escitalopram Oxalate: Isolation and Synthesis of Novel Impurities,"During process optimization of Escitalopram oxalate novel impurities, 6 and 7 were observed, which were isolated and characterized, and the proposed structure was confirmed by chemical synthesis. Investigation of the cause of impurities formation improved the yield and purity of the drug product during the bulk API synthesis.",10.1021/op300039c,2012-04-16,0.6360409886595187
Tetrahedron,Synthesis and cross coupling of a highly substituted 2-pyridylboronate: application to the large scale synthesis of a mineralocorticoid antagonist,,10.1016/j.tetlet.2011.10.052,2011-10-25,0.6360285586995208
Synthesis,Bryophyte Constituents; 6: Synthesis of Herbertene-Derived Sesquiterpenes from Herberta adunca,"All articles of this category Efficient total syntheses are described for the racemic sesquiterpenes herbertenolide (2) , α -herbertenol (3) and β -herbertenol (4) from Herberta adunca . ent -Herbertenolide [(+) -2 ] was prepared from enantiopure (-)-ethyl (1 R )-1-methyl-2-oxocyclopentanecarboxylate (9) obtained from ethyl 2-oxocyclopentanecarboxylate (19) via reduction with baker’s yeast. bryophyte constituents - sesquiterpenes - herbertene - enantioselective synthesis - baker’s yeast",10.1055/s-1996-4309,1996-07-01,0.6360275538539482
Organic Letters,"Spongistatin Synthetic Studies. An Efficient, Second-Generation Construction of an Advanced ABCD Intermediate","[reaction: see text] A short, efficient, and stereocontrolled synthesis of (-)-4, an advanced ABCD subunit of the spongistatins, has been achieved. Central to the synthetic strategy is the multicomponent linchpin union of silyl dithianes with epoxides to access both the AB and CD fragments. Fragment coupling was then achieved via an efficient stereoselective aldol reaction. The linear sequence required 22 steps and proceeded in 4.0% overall yield.",10.1021/ol017273z,2002-02-02,0.6360097898633855
Tetrahedron,"Palladium-catalyzed diastereoselective synthesis of β,β-diarylpropionic acid derivatives and its application to the total synthesis of ( R )-tolterodine and the enantiomer of a key intermediate for MK-8718",,10.1016/j.tetlet.2017.12.082,2017-12-30,0.636005623045058
Organic Letters,"Facile Synthesis of Bicyclic Amidines and Imidazolines from 1,2-Diamines","A facile synthesis of chiral bicyclic amidines and imidazolines from readily available 1,2-diamines has been developed. The reported synthetic strategy relies on an intramolecular cyclization which involves a carboxylic amide derived imidoyl chloride as a key intermediate and aniline serving as a leaving group.",10.1021/ol101747n,2010-08-20,0.6360039871216463
Journal of Organic Chemistry,Total Synthesis of (+)-Galactostatin. An Illustration of the Utility of the Thiazole-Aldehyde Synthesis,"The natural aza sugar (+)-galactostatin (+)-1 has been prepared from d-serine by sequential installation of chiral 1C and 2C units employing thiazole-based reagents. Thus, the d-serine-derived methyl ester 3 was transformed by 2-thiazolyllithium (4) into the thiazolyl amino ketone 5 which, via syn stereoselective carbonyl reduction and thiazolyl-to-formyl conversion, gave the first key intermediate, the α-hydroxy β-amino aldehyde 10. The olefination of this compound by [(2-thiazolyl)-methylene]triphenylphosphorane (14) followed by osmium tetroxide cis dihydroxylation of the resulting alkene E-16 and cleavage of the thiazole ring produced the second key intermediate, the amino- and hydroxyl-protected 5-deoxy-5-amino-d-galactose 20. The removal of all protecting groups of this compound afforded the target aza sugar (+)-1 in 17.3% overall yield from 3. © 1995, American Chemical Society. All rights reserved.",10.1021/jo00120a017,1995-07-01,0.6359975993360869
Synthesis,Improved Synthesis of Thromboxane A2 Receptor Antagonists with a Dibenzoxepin Ring System,"All articles of this category Two derivatives of sodium ( E )-11-[2-(1-benzimidazolyl)ethylidene]-11-oxo-6,11-dihydrodibenz[ b,e ]oxepin-2-carboxylate, novel non-prostanoid thromboxane A 2 (TXA 2 ) receptor antagonists, were synthesized from methyl 11-oxo-6,11-dihydrodibenz[ b,e ]oxepin-2-carboxylate. The carbonyl group at C11 was converted into a formylmethylene, then into a 1-azadiene moiety by reaction with a 2-aminoformanilide derivative. Stereo- and regioselective elaboration of the unsymmetrical imidazoles was achieved through a sequence of the transformation of E,Z -1-azadiene intermediates to E isomers under acidic conditions followed by cyclization to imidazoles. ( E )-selective - regioselective - 1-azadiene - dibenzoxepin - thromboxane A 2 antagonist",10.1055/s-1995-4088,1995-10-01,0.6359897238514676
Journal of Organic Chemistry,Synthesis of Racemic <i>cis</i>-5-Hydroxy-3-phthalimidoglutarimide. A Metabolite of Thalidomide Isolated from Human Plasma,"[reaction: see text] A synthesis of the glutarimide-derived metabolite of thalidomide, 5'-hydroxythalidomide (2), is described. The synthesis employed the lactone derivative of N-benzyloxycarbonyl (CBZ)-protected 4-hydroxyglutamic acid 12, which is prepared by a de novo route from diethyl acetamidomalonate. The reaction of 12 with 4-methoxybenzylamine gave the corresponding isoglutamine, which then provided the key CBZ-protected N-PMB-glutarimide 14 after dehydration. Deprotection of both the CBZ and PMB groups followed by phthalimidation and deacetylation of the 3-amino-5-acetoxyglutarimide 16 afforded 2.",10.1021/jo0514772,2005-10-21,0.6359847159591269
Angewandte Chemie International Edition,Asymmetric Total Synthesis of the Epoxykinamycin FL‐120 B′,"Turn up the heat: The synthesis of the title compound was achieved and a route to epoxide-containing diazobenzofluorenes, which could potentially serve as monomers to the dimeric lomaiviticins, was established. Key steps to construct the FL-120B′ core structure include Sharpless asymmetric epoxidation, Stille coupling, and intramolecular Friedel–Crafts acylation of atropisomeric carboxylic acids at elevated temperatures.",10.1002/anie.201104504,2011-08-30,0.6359836738367924
Journal of the American Chemical Society,Toward a General Route to the Eunicellin Diterpenes:  The Asymmetric Total Synthesis of Deacetoxyalcyonin Acetate,"A novel approach to the hydroisobenzofuran core utilizing a TiCl4-mediated [4+3] annulation is reported. This [4+3] annulation protocol provides a short, general route to the hydroisobenzofuran core present in the eunicellin diterpenes. Using this annulation, a short synthesis (17 steps) of deacetoxyalcyonin acetate, a member of the eunicellin family, has been achieved.",10.1021/ja0398464,2004-01-27,0.6359822211582276
Synthesis,Iterative Iodocyclization: Total Synthesis of Polyrhacitide B,"A highly stereoselective total synthesis of polyrhacitide B is reported. Key reactions are an iodocyclization protocol developed in our group, the Maruoka asymmetric allylation, the Bartlett–Smith iodocarbonate cyclization, and iodolactonization.",10.1055/s-0033-1341154,2014-04-11,0.635960267838992
Synlett,An Expedient Total Synthesis of (-)-Cladospolide A,"A simple and efficient total synthesis of (-)-cladospolide A is described here, which involves either olefin cross metathesis or Julia-Kocienski olefination and Yamaguchi macrolactonization as key steps.",10.1055/s-0029-1217737,2009-08-27,0.635958794541275
Organic Process Research & Development,"Process Research for the Synthesis of RWJ-51204, A Novel Anxiolytic Agent","RWJ-51204, the lead compound in our pyrido [1,2- a ] benzimidazole (PBI) series, was shown to exhibit anxiolytic efficacy in animal models at doses which did not cause central nervous system side effects commonly observed with other anxiolytic agents. To prepare supplies of drug substance for early toxicological and clinical studies, we needed to develop a safe and scaleable synthesis. Our main focus was to improve the last two steps of the process which involved formation of the penultimate carboxamide intermediate followed by alkylation using potentially toxic chloromethyl ethyl ether. Due to safety issues concerning storage and handling of this reagent during the large scale synthesis, we investigated alternate routes to minimize potential exposure risks. The process research carried out for the final steps that led to the safe and cost-effective multi-kilogram synthesis of RWJ-51204 is described herein.",10.1021/op990182l,1999-06-18,0.6359550093918618
Tetrahedron,Thermal electrocyclic spirocyclization of p-benzoquinone imines: A novel synthetic route to trifluoromethylated spirodiazacarbocycles,,10.1016/s0040-4039(00)77072-9,1994-07-01,0.6359318642252454
Organic Letters,Synthesis of (−)-Lasubine(I) via a Planar Chiral (η<sup>6</sup>-Arene)Cr(CO)<sub>3</sub>] Complex,"Key steps of the synthesis of the Lythracaea alkaloid (--)-lasubine(I) are the formation of an enantiopure planar chiral arylaldehyde tricarbonylchromium complex and highly diastereoselective aza-Diels-Alder cycloaddition and intramolecular radical cyclization reactions to afford a quinolizidinone intermediate. Ketone reduction, desilylation, and decomplexation yield the enantiomerically pure product.",10.1021/ol006092e,2000-06-01,0.6359023649566485
Organic Letters,Synthesis of (−)-Lasubine(I) via a Planar Chiral [(η<sup>6</sup>-arene)Cr(CO)<sub>3</sub>] Complex,"Key steps of the synthesis of the Lythraceae alkaloid (−)-lasubine(I) are the formation of an enantiopure planar chiral arylaldehyde tricarbonylchromium complex and highly diastereoselective aza-Diels−Alder cycloaddition and intramolecular radical cyclization reactions to afford a quinolizidinone intermediate. Ketone reduction, desilylation, and decomplexation yield the enantiomerically pure product.",10.1021/ol991158v,1999-11-18,0.6359023649566485
Angewandte Chemie International Edition,Asymmetric Total Synthesis of the Complex Polycyclic Xanthone FD‐594,"A highly convergent approach was developed to achieve the first asymmetric and scalable total synthesis of FD-594, a complex polycyclic xanthone natural product from Streptomyces sp. TA-0256, in a longest linear sequence (LLS) of 20 steps. The trans-9,10-dihydrophenanthrene-9,10-diol fragment (B-C-D ring) was generated through a new strategy involving asymmetric dihydroxylation followed by Cu-mediated oxidative cyclization. Late-stage stereoselective glycosylation assembled the angular hexacyclic framework with a β-linked 2,6-dideoxy trisaccharide fragment.",10.1002/anie.201915787,2020-01-13,0.6358988702573453
Organic Letters,Synthesis of the <i>N</i>-Acetylcysteamine Thioester of <i>s</i><i>eco</i>-Proansamitocin,"[structure: see text] The enantioselective total synthesis of the N-acetylcysteamine thioester of seco-proansamitocin, a key biosynthetic intermediate of the highly potent antitumor agent ansamitocin, is described, which twice utilizes the Nagao acetate aldol reaction, as well as an indium-mediated alkynylation of a benzyl bromide followed by carboalumination. The key step is a Heck reaction between two terminal alkenes for merging the two major fragments.",10.1021/ol052588q,2005-12-14,0.6358930496080935
Journal of Organic Chemistry,"A Novel Synthetic Method of the (±)-(3aα,8aα)-Ethyl 8β-Hydroxy-6β-methyl-2-oxooctahydro-2<i>H</i>-cyclohepta[<i>b</i>]furan-3α- carboxylate and Its Chemical Transformation to (±)-(3aα,8aα)-3α,6β-Dimethyl-3,3a,4,5,6,8a-hexahydro-2<i>H</i>- cyclohepta[<i>b</i>]furan-2-one, (+)- and (−)-7β-(2-Acetoxy-1α-methylethyl)-4β-methyl-2-cyclohepten-1β-ol, and (+)- and (−)-7β-(2-Acetoxy-1α-methylethyl)-4β-methyl-2-cyclohepten-1-one. Possible Common Synthetic Intermediates for Pseudoguaianolides, 4,5-Secopseudoguaianolides, Guaianolides, 4,5-Secoguaianolides, and Octalactins","The catalytic hydrogenation of ethyl 8-hydroxy-6-methyl-2-oxo-2 H -cyclohepta[ b ]furan-3-carboxylate ( 6 ), which was derived regioselectively from 4-methyltropolone ( 1 ) in four steps in 62% overall yield, gave (3aα,8aα)-ethyl 8β-hydroxy-6β-methyl-2-oxooctahydro-2 H -cyclohepta[ b ]furan-3α-carboxylate ( 8b ) in 45% yield. It is noteworthy that four asymmetric centers newly introduced on the seven-membered ring of 8b were controlled to be syn-oriented by the single operation. The latter was transformed to (3aα,8aα)-3α,6β-dimethyl-3,3a,4,5,6,8a-hexahydro-2 H -cyclohepta[ b ]furan-2-one ( 17a ) in 77% overall yield in five steps. Reduction of 17a with LiAlH 4 gave (±)-7β-(2-hydroxy-1α-methylethyl)-4β-methyl-2-cyclohepten-1β-ol ( 22 ), whose enantioselective acetylation was achieved by vinyl acetate in the presence of Lipase PS to give (+)-7β-(2-acetoxy-1α-methylethyl)-4β-methyl-2-cyclohepten-1β-ol ( 24 ) in 48% yield (93% ee) or in 52% yield (77% ee) and (−)- 22 in 52% yield (70% ee) or 44% yield (89% ee). Oxidation of (+)- 24 with MnO 2 gave (−)-7β-(2-acetoxy-1α-methyl ethyl)-4β-methyl-2-cyclohepten-1-one (−)-( 25 ). Similarly, acetylation of (−)- 22 followed by oxidation of resulting (−)- 24 gave (+)- 25 .",10.1021/jo971529q,1998-02-01,0.6358839006370866
Organic Letters,Total Synthesis of Diocollettines A via an Acid-Promoted Oxa-Michael–Aldol–Acetalization Cascade,"A diastereo- and enantioselective total synthesis of diocollettines A with an unusual oxygen-containing tricyclic ring system has been achieved in 63% overall yield from commercially available 3-phenylpropanal via four steps. The key feature of the present synthesis is an exclusively diastereoselective cascade sequence composed of a trans -selective oxa-Michael addition of 1,3-dihydroxyacetone to a 2,3-dihydropyrylium ion intermediate, intramolecular aldol-type reaction, and intramolecular acetalization.",10.1021/acs.orglett.9b04074,2019-12-03,0.6358729806402746
Journal of Organic Chemistry,A Versatile Synthesis of Fumaquinone,"Fumaquinone, a novel prenylated naphthoquinone antibiotic, was synthetized from ethyl acetoacetate in three steps (58% overall yield). The key step of the synthesis is the construction of the naphthoquinone skeleton by a regioselective Diels-Alder reaction between a 2-alkyl 1,3-bis(trimethylsilyloxy)-1,3-diene derivative and a bromoquinone. This short and versatile approach confirms the structure of fumaquinone and allows the synthesis of derivatives at the C-6 position.",10.1021/jo100779z,2010-06-28,0.6358442738038109
Organic Letters,An Approach to Pancratistatins via Ring-Closing Metathesis:  Efficient Synthesis of Novel 1-Aryl-1-deoxyconduritols F,"Structurally novel cyclitols, 1-aryl-1-deoxyconduritols F, were efficiently prepared from d-xylose, utilizing RCM as a key step. Various aromatic residues were incorporated in the cyclitol skeleton with total stereochemical control, utilizing a diastereoselective aryl cuprate addition to a gamma-alkoxy enoate. The synthetic route establishes a firm foundation for a practical synthesis of the antitumor alkaloid pancratistatin and its aryl analogues. [structure: see text]",10.1021/ol049942p,2004-01-31,0.6358373170367156
Angewandte Chemie International Edition,A Concise Total Synthesis of (±)‐Vigulariol,From the deep: Vigulariol has been efficiently synthesized in 20 steps and 4.0 % overall yield from commercially available starting materials. Key to the synthesis was the use of copper(II) hexafluoroacetylacetate [Cu(hfacac)2] to form the oxabicyclo[6.2.1]undecene system (see scheme; TBS=tert-butyldimethylsilyl). The strategy should provide access to other members of the cladiellin family.,10.1002/anie.200603880,2006-12-05,0.6358238888921598
Synlett,Synthesis of Isofagomine anda New C<sub>6</sub> Pyrrolidine Azasugar with Potential BiologicalActivity,"An efficient asymmetric synthesis of isofagomine, based on a precursor containing three differentiated hydroxyl functions, is described. The side product in the key alkylation step is converted into (2S,3R,4R)-2,4-bis(hydroxymethyl)-3-hydroxypyrrolidine, a new C-6 pyrrolidine azasugar, which inhibits alpha-glucosidase from yeast.",10.1055/s-2008-1078280,2008-08-22,0.6358116396718789
Organic Letters,Synthesis of (+)-Voglibose,"A concise asymmetric synthesis of voglibose, a natural product derivative and an alpha-glucosidase inhibitor with antihyperglycemic activity, was produced from an O-arylated lactic acid derivative in only seven steps. This approach was based on an oxidative phenol dearomatization process promoted by a hypervalent iodine reagent, a chiral auxiliary serving as a protecting group and allowing the asymmetric formation of the target, and a key hydrolysis leading to the formation of several contiguous stereocenters and removal of the chiral auxiliary.",10.1021/acs.orglett.5c00647,2025-03-15,0.6358106889020987
Journal of Organic Chemistry,"Synthesis of Sequence-Selective C8-Linked Pyrrolo[2,1-<i>c</i>][1,4]benzodiazepine DNA Interstrand Cross-Linking Agents","An efficient convergent synthesis of a homologous series of C8-linked pyrrolobenzodiazepine dimers with remarkable DNA interstrand cross-linking activity and potent in vitro cytotoxicity is reported. The ""amino thioacetal"" cyclization procedure was used to produce the electrophilic DNA-interactive N10-C11 imine moiety during the final synthetic step. In order to construct the key A-ring fragments (9a-d), a versatile convergent approach has been developed to join two units of vanillic acid with alpha,omega-dihaloalkanes of varying length to provide the required bis(4-carboxy-2-methoxyphenoxy)alkanes while avoiding the formation of mixtures of monoalkylated and bisalkylated products.",10.1021/jo951631s,1996-11-15,0.6357922200013033
Synlett,Total Synthesis of 8-Methoxygoniodiol via Chiron Approach,A stereoselective synthesis of 8-methoxygoniodiol is accomplished using readily available δ-gluconolactone as a chiral source. The stereoselective addition of aryl Grignard reagent on aldehyde and regioselective opening of chiral epoxide by ethyl propiolate are the key steps involved in this synthesis.,10.1055/s-2008-1072511,2008-03-17,0.6357897183659482
Journal of Organic Chemistry,Synthetic Application of Acylnitroso Diels−Alder Derived Aminocyclopentenols:  Total Synthesis of (+)-Streptazolin,"Concise total syntheses of (+)-streptazolin 1 and its more stable dihydro derivative 2 were accomplished via an intramolecular aldol condensation strategy starting from readily available aminocyclopentenol (-)-7. The synthetic sequence included reductive amination, stereoselective epoxidation, intramolecular aldol (and condensation) reaction, and Wittig reaction. The overall yield for dihydro derivative 2 from aminocyclopentenol (-)-7 was about 7% for a total of 14 steps.",10.1021/jo048606j,2004-11-12,0.6357771753281688
Organic Letters,Diastereoselective Palladaelectro-Catalyzed Construction of Bromomethyl Morpholines as Key Step To Access Morpholino Homonucleosides,"A synthetic protocol for the preparation of a new class of morpholino homonucleosides in enantiopure form starting from readily available 1,2-aminoalcohols or glycidol has been developed. Key intermediates of the synthetic sequence are 2-bromomethyl morpholines, diastereoselectively achieved from the corresponding alkenols by palladaelectro-catalyzed alkoxybromination of unactivated alkenes. The so obtained bromo derivatives are in turn susceptible to functionalization with nucleic bases for easy access to morpholino homonucleosides.",10.1021/acs.orglett.4c01790,2024-07-22,0.6357760378983682
Organic Letters,Toward the Synthesis of Fluorinated Analogues of HCV NS3/4A Serine Protease Inhibitors Using Methyl α-Amino-β-fluoro-β-vinylcyclopropanecarboxylate as Key Intermediate,"Synthesis of fluorocyclopropyl building blocks, which constitute the core of various therapeutic agents against the hepatitis C virus, is described. The relevant methyl α-amino-β-fluoro-β-vinylcyclopropanecarboxylate has been used as a key intermediate for the total synthesis of a fluorinated analogue of Simeprevir (TMC 435), a HCV NS3/4A protease inhibitor.",10.1021/acs.orglett.5b01216,2015-06-08,0.6357702438439176
Tetrahedron,Oxidative rearrangement of 2-spirochromanones: a novel route for the synthesis of tetrahydroxanthones,,10.1016/0040-4039(91)80100-k,1991-09-01,0.6357479586733858
Journal of Organic Chemistry,"Total Synthesis of an Antitumor Agent, Mucocin, Based on the “Chiron Approach”","The total synthesis of a powerful antitumor acetogenin, mucocin (1), was achieved through a palladium-catalyzed cross-coupling reaction of the THP-THF fragment 2 and a terminal butenolide 3. The key process for construction of the fragment 2 was chelation-controlled addition of ethynylmagnesium chloride to disilyl aldehyde 23a and condensation of the alkyllithium prepared therefrom with THP aldehyde 4 in the presence of CeCl(3). Synthesis of the lactone 3 relied on a novel approach by taking advantage of a radical cyclization of acyclic selenocarbonate 6. The three building blocks 4, 5a, and 6 were prepared stereoselectivly from D-galactose (7), 2,5-anhydro-D-mannitol (8), and L-rhamnose (9), respectively. A new and efficient method for desymmetrization of the C(2)-symmetrical compound 8 is also described.",10.1021/jo020211h,2002-07-09,0.6357259107323482
Organic Process Research & Development,Methodologies for the Formation of 2-Substituted Oxetanes: Synthesis of (<i>S</i>)-Oxetan-2-ylmethyl Tosylate,"The compound ( S )-oxetan-2-ylmethyl tosylate 1 was identified as a key synthetic fragment for the introduction of the 2-substituted oxetane functionality in potential drug candidates under development in our laboratories. The focus of this paper is to highlight methodologies evaluated in our quest for synthetic routes to 2-substituted oxetanes suitable for enabling manufacture. Of the five routes investigated, three (Route 1A, Route 2, and Route 3) were successfully demonstrated in the laboratory. Subsequently, Route 3 was executed at scale to deliver metric ton quantities of the oxetane tosylate 1 as a solution in EtOAc, which was integrated into the synthesis of 2 and aforementioned drug candidates.",10.1021/acs.oprd.4c00514,2025-01-29,0.6357200497403213
Angewandte Chemie International Edition,A Ten‐Step Total Synthesis of Speradine C,"The first total synthesis of speradine C has been achieved in only ten steps from a commercially available 4-bromoindole. Salient features of the work are the formation of four rings through three cyclizations, namely a bioinspired [3+2] annulation to form the C/D rings, an NCS-mediated oxidation to construct the E ring, and a Ru-catalyzed ketohydroxylation to assemble the F ring. This work highlights how strategic ring constructions can streamline the synthesis of polycyclic compounds.",10.1002/anie.201902004,2019-03-18,0.6357154705447956
Tetrahedron,A new one-step method for oxaadamantane synthesis,,10.1016/0040-4039(96)01202-6,1996-08-01,0.6357062765519592
Synlett,Efficient Asymmetric Synthesis of (<i>S</i>)-2-Methylasparagine,"All articles of this category ( S )-2-methylasparagine was prepared from both (5 S ,6 R )-4-(benzyloxycarbonyl)-5,6-diphenyl-2,3,5,6-tetrahydro-4H-1,4-oxazin-2-one ((-)- 1 ) and its antipode ((+)- 1 ) via stereoselective glycine enolate alkylation as a key step. chiral template - asymmetric synthesis - ( S )-2-methylasparagine - quaternary amino acid - stereoselective alkylation",10.1055/s-1998-1884,1998-10-01,0.6356877929862866
Synthesis,Practical and Green Synthesis of Combretastatin A-4 and Its Prodrug CA4P Using Renewable Biomass-Based Starting Materials,"A practical and green protocol for the synthesis of vascular disrupting agent combretastatin A-4 (CA4) and its water soluble prodrug CA4P is described. Starting from the biomass-based compound anethole, which is abundantly and sustainably available from Chinese star anise (Illicium verum Hook. f.), the key intermediate 3-hydroxy-4-methoxyphenylacetic acid can be obtained within five steps. Perkin condensation between this acid and another naturally derived compound 3,4,5-trimethoxybenzaldehyde, followed by decarboxylation gives combretastatin A-4 in good overall yield. The phosphate produrg CA4P can be prepared under simple and mild conditions in a sequential one-pot two-step reaction.",10.1055/s-0030-1258358,2010-12-08,0.6356842736448658
Journal of Organic Chemistry,Synthesis of Selective Estrogen Receptor Degrader GDC-0810 via Stereocontrolled Assembly of a Tetrasubstituted All-Carbon Olefin,"We report an efficient synthesis of GDC-0810 on the basis of a sequence involving a highly stereoselective lithium tert-butoxide-mediated enolization-tosylation (≥95:5 E: Z) and a Pd-catalyzed Suzuki-Miyaura cross-coupling as key steps. Global deprotection, pyrrolidine salt formation, and final active pharmaceutical ingredient (API) form control/isolation produced GDC-0810 free acid in a 40% overall yield with >99.0% purity as ascertained by HPLC analysis.",10.1021/acs.joc.8b01551,2018-09-10,0.6356778886784084
Journal of Organic Chemistry,Asymmetric Synthesis of (+)-Negamycin,"An asymmetric synthesis of the antibiotic (+)-negamycin (1) has been achieved, starting from commercially available (5R,6S)-4-(benzyloxycarbonyl)-5,6-diphenyl-2,3,5,6-tetrahydro-4H-1,4-oxazin-2-one (2). The synthesis involved the stabilized Wittig olefination of the lactone carbonyl group of 2 and subsequent asymmetric hydrogenation to generate the corresponding all-syn oxazine 4 with excellent diastereoselectivity. Conversion of 4 into beta-alkoxy imine 7 and subsequent CeCl3-promoted chelation-controlled allylation of 7 generated the corresponding homoallylamine 8 with good diatereoselectivity, which was readily converted into (+)-negamycin (1) in 25% overall yield over 11 steps.",10.1021/jo025636i,2002-08-02,0.6356645677016317
Journal of Organic Chemistry,Total Synthesis of (+)-Acutiphycin,"Synthetic studies toward the total synthesis of (+)-acutiphycin (1) resulted in the discovery of additive-free, highly regioselective nickel-catalyzed reductive coupling reactions of aldehydes and 1,6-enynes and the construction of an advanced intermediate in studies directed toward the synthesis of 1. Ultimately, although not employing the nickel-catalyzed reaction, a highly convergent total synthesis of (+)-acutiphycin featuring an intermolecular SmI2-mediated Reformatsky coupling reaction and macrolactonization initiated by a retro-ene reaction of an alkoxyalkyne was achieved. The resulting synthesis was 18 steps in the longest linear sequence from either methyl acetoacetate or isobutyraldehyde.",10.1021/jo701821h,2007-11-07,0.6356637150644181
Organic Letters,Total Synthesis of Deoxy-solomonamide B by Mimicking Biogenesis,"A total synthesis of Deoxy-solomonamide B was accomplished starting from tryptophan in an efficient manner by mimicking the proposed biogenetic route. The present synthesis utilizes a crotylation, oxidative cleavage of the indole moiety, and macrolactamization as key steps. The use of the indole nucleus as a masked anthranilic acid unit paves the way for the easy synthesis of related macrocycles and natural products where the ortho-acyl aniline moiety is embedded into them, which otherwise is difficult to synthesize.",10.1021/ol503011g,2014-11-13,0.6356581579418753
Organic Process Research & Development,Development of a Novel Process for the Preparation of the Anti-Inflammatory Drug Betamethasone Sodium Phosphate,"In this paper, we report our efforts for the development of a novel and improved preparation of the anti-inflammatory steroidal active pharmaceutical ingredient, namely, betamethasone sodium phosphate. Starting from commercially available betamethasone, the synthetic strategy involved the mesylation of the hydroxyl group at C21 position, followed by the key phosphorylation reaction of the mesylate derivative with potassium di- tert -butyl phosphate, the hydrolysis of the di- tert -butyl ester intermediate under mild acidic conditions, and the final salification. The developed process allowed us to obtain the desired betamethasone sodium phosphate in 68% overall yield at multi-kg scale ≥ 99.9% HPLC purity. Cost-effectiveness of the process, impurity profiling, and material quality are also discussed.",10.1021/acs.oprd.2c00329,2023-01-03,0.6356319950461896
Tetrahedron,A novel synthesis of isoindolobenzazepine alkaloids: application to the synthesis of lennoxamine,,10.1016/s0040-4039(00)01390-3,2000-10-01,0.6356249031054014
Organic Process Research & Development,"Practical Synthesis of 3-Amino-4,5-dimethylisoxazole from 2-Methyl-2-butenenitrile and Acetohydroxamic Acid","3-Amino-4,5-dimethylisoxazole was prepared from technical-grade 2-methyl-2-butenenitrile and acetohydroxamic acid in a 62% overall yield on a multimole scale. The key features of this synthesis are (1) DBU treatment of the technical-grade nitrile mixture to provide a starting material of acceptable purity and (2) use of acetohydroxamic acid as an N-protected hydroxylamine equivalent. This operationally simple method provides the title compound in reasonable overall yield and free of contamination from the isomeric 5-amino-3,4-dimethylisoxazole.",10.1021/op060239l,2007-03-01,0.6356248928609614
Journal of Organic Chemistry,Four-Step Total Synthesis of (+)-Euphococcinine and (±)-Adaline,"A four-step enantiospecific total synthesis of bicyclic homotropinone alkaloid euphococcinine and a racemic synthesis of adaline were reported. Key reactions in the synthesis are the diastereoselective addition of a Wittig phosphorene to the ketimines derived from Davis-Ellman sulfinamides, ring-closing metathesis, and intramolecular Michael reactions.",10.1021/acs.joc.1c00938,2021-08-19,0.635619295792218
Tetrahedron,A novel method for the efficient synthesis of 2-arylamino-2-imidazolines,,10.1016/s0040-4039(00)01102-3,2000-08-01,0.6356190219587406
Tetrahedron,"A novel and efficient method for the synthesis of 1,2-diazetidines",,10.1016/j.tetlet.2006.07.075,2006-08-09,0.6356190219587406
Journal of the American Chemical Society,Alkynyliodonium Salts in Organic Synthesis. Application to the Total Synthesis of the Tropoloisoquinoline Alkaloid Pareitropone,"The synthesis of the tropoloisoquinoline alkaloid pareitropone has been accomplished in 14 steps from 2,3,4-trimethoxybenzoic acid. The key transformations include the generation of an alkylidenecarbene intermediate through intramolecular addition of a tosylamide anion to an alkynyliodonium salt, and the cycloaddition of that carbene to a peri positioned aromatic ring to afford a cycloheptatrienylidene product featuring the intact pareitropone skeleton.",10.1021/ja0277430,2002-09-04,0.6356147467199896
Synlett,Toward the Total Synthesis of Schinortriterpenoids: Construction of the All-cis-Substituted Cyclopropane Unit,"Abstract As a step toward a total synthesis of pre-schisanartanins and arisanlactones, we successfully synthesized a right fragment of Schisandra nortriterpenoids bearing a distorting all-cis-substituted cyclopropane from a chiral lactone. The key step in this synthesis was the diastereoselective construction of an all-cis-substituted cyclopropane through a Negishi coupling using an amide as a directing group.",10.1055/a-2102-8014,2023-05-30,0.6356112621163154
Organic Letters,"Development of a Practical, Asymmetric Synthesis of the Hepatitis C Virus Protease Inhibitor MK-5172","The development of a practical, asymmetric synthesis of the hepatitis C virus (HCV) protease inhibitor MK-5172 (1), an 18-membered macrocycle, is described.",10.1021/ol401864t,2013-08-06,0.6356099659398727
Organic Letters,Asymmetric Synthesis of <i>ent</i>-Fissistigmatin C,"The asymmetric synthesis of ent -fissistigmatin C is successively accomplished in 12 steps (longest linear sequence (LLS)). Relying on the enantioselective coupling of aliphatic aldehyde with 2-hydroxychalcone promoted by cooperative organocatalysts, the pivotal linkage of ent -fissistigmatin C between the flavonoid and the sesquiterpenoid fragment was stereoselectively established. An unprecedented final-stage radical cascade was also featured in this synthesis, which enabled the simultaneous establishment of the trans -decalin framework via forging two consecutive C–C bonds in one step.",10.1021/acs.orglett.0c03766,2020-12-18,0.6355970027793398
Journal of the American Chemical Society,Concise Total Synthesis of (+)-Pleiocarpamine and Convergent Total Syntheses of (+)-Voacalgine A and (+)-Bipleiophylline via an Aerobic Oxidative Coupling,"The stereocontrolled total synthesis of (+)-pleiocarpamine and the total syntheses of (+)-voacalgine A and (+)-bipleiophylline have been achieved. The scalable and concise 10-step synthesis of (+)-pleiocarpamine features construction of stereochemistry at the C16 position by radical cyclization and that of the highly strained cage-like structure via Pd-catalyzed intramolecular aromatic C–H functionalization. By modifying the biomimetic aerobic oxidative coupling of tryptophane derivatives catalyzed by FePc(CO 2 H) 8, the oxidative coupling of the synthesized (+)-pleiocarpamine with pyrocatechuic acid was established to produce (+)-voacalgine A. The total synthesis of (+)-bipleiophylline was completed by the second coupling of (+)-voacalgine A with (+)-pleiocarpamine or one-pot couplings of 2 equiv of (+)-pleiocarpamine with pyrocatechuic acid.",10.1021/jacs.3c05811,2023-07-24,0.635593905782041
Organic Letters,Total Synthesis of Ecumicin,"The first total synthesis of the potent anti-mycobacterial cyclic depsipeptide natural product ecumicin is described. Synthesis was achieved via a solid-phase strategy, incorporating the synthetic non-proteinogenic amino acids N -methyl-4-methoxy- l -tryptophan and threo -β-hydroxy- l -phenylalanine into the growing linear peptide chain. The synthesis employed key on-resin esterification and dimethylation steps as well as a final macrolactamization between the unusual N -methyl-4-methoxy- l -tryptophan unit and a bulky N -methyl- l -valine residue. The synthetic natural product possessed potent antimycobacterial activity against the virulent H37Rv strain of Mycobacterium tuberculosis (MIC 90 = 312 nM).",10.1021/acs.orglett.7b03967,2018-02-07,0.6355872113401226
Organic Letters,Total Synthesis of (−)-18-<i>epi</i>-Peloruside A: An Alkyne Linchpin Strategy,"A convergent synthetic route toward cytotoxic agent peloruside A that hinges on the use of an alkyne linchpin to assemble the natural product is described. Other highlights of this synthesis include an asymmetric desymmetrization reaction of a 1,3-diol, a one-pot conversion of a dibromoolefin to a stereodefined enone, and a diastereoselective aldol condensation. Misassignment of the absolute stereochemistry of the C18 stereocenter in our synthesis provided the natural product epimeric at the C18 ethyl stereocenter.",10.1021/ol4024997,2013-10-04,0.6355870318016871
Tetrahedron,"Asymmetric synthesis of (s)-methyl-3-hydroxyalkanoates from ketene and 2,2-dichloroaldehydes via 4-(1,1-dichloroalkyl)-2-oxetanones",,10.1016/s0040-4039(00)98780-x,1985-01-01,0.6355843740182886
Synlett,"Asymmetric Synthesis of 2,4,6-Trideoxy-4-(dimethylamino)-3-C-methyl-l-lyxohexopyranose (Lemonose)",International audience,10.1055/s-0030-1259531,2011-02-08,0.6355843740182886
Organic Letters,Total Synthesis of Viridiofungins A and B,"The total synthesis of viridiofungins A ( 1 ) and B ( 2 ) via β-lactone 3 in 13 steps is reported. Key steps included an HF-mediated rearrangement of cyclobutene diester 9 to form a bicyclic lactone 6, an olefin cross metathesis between disubstituted alkene 3 and alkene 4 in which isomerization was suppressed, and a novel β-lactone ring opening to form the amide. Deprotection then gave either viridiofungin A ( 1 ) or B ( 2 ) in high yield.",10.1021/acs.orglett.1c00971,2021-04-22,0.6355835705414613
Organic Letters,"Total Synthesis of the β-Catenin Inhibitor, (−)-Agelastatin A: A Second-Generation Approach Based on Radical Aminobromination","The second-generation approach to (-)-agelastatin A has been established. The present strategy features the FeBr(2)-mediated radical cyclization of 2-cyclopentenyloxycarbonyl azide that allows for the stereoselective installation of a cis-vicinal aminobromo functionality suitable for producing the BCD-ring system of agelastatin A. The aminobromination method streamlines access to oxazolidinone, a key intermediate in the previously reported synthesis, thereby culminating in the new total synthesis of (-)-agelastatin A.",10.1021/ol9012684,2009-07-09,0.6355734884583498
Tetrahedron,Highly efficient and stereocontrolled synthetic route to enantiopure ACC derivatives,,10.1016/s0040-4039(00)78226-8,1994-08-01,0.6355685888440572
Tetrahedron,En route to the total synthesis of tashironin: on the exercise of stereochemical control by a methyl group in mediating remote cyclization reactions,,10.1016/j.tetlet.2004.11.148,2004-12-24,0.635560773818551
Journal of Organic Chemistry,Novel Stereocontrolled Addition of Allylmetal Reagents to α-Imino Esters:  Efficient Synthesis of Chiral Tetrahydroquinoline Derivatives,"To prepare in multigram scale new antagonists of the glycine binding site associated to the NMDA receptor, an efficient distereoselective route was set up. The addition of suitable allyltin reagents to chiral N-aryl alpha-imino esters (R-(+)-tert-butyl lactate used as chiral auxiliary), gave the corresponding alpha amino acid-type derivative in high chemical yield and optical purity. This allylation reaction represents a novel example of efficient long-range stereodifferentiation process. In the last part of the synthesis, a regioselective Heck-type cyclization reaction enabled preparation of the target tetrasubstituted exocycle and trisubtituted endocycle double bond derivatives.",10.1021/jo020327d,2002-09-19,0.6355578729230131
Journal of Organic Chemistry,An Improved Synthesis of Pyridine−Thiazole Cores of Thiopeptide Antibiotics,The oxidation of 2-methylthiazoles to 2-formylthiazoles simplifies the implementation of the Bagley variant of the Bohlmann-Rahtz reaction as a key step in a concise new route to pyridine cores of thiopeptide antibiotics.,10.1021/jo900950x,2009-07-02,0.6355343575577893
Tetrahedron,A synthesis of the γ-secretase inhibitor BMS-708163,,10.1016/j.tetlet.2010.10.025,2010-10-15,0.6355138760167058
Tetrahedron,Total synthesis of khellinone and khellin the pyrogallol route regiospecific methoxylation of a benzofuran,,10.1016/s0040-4039(00)99051-8,1985-01-01,0.6355064777170115
Journal of Organic Chemistry,Enantioselective Synthesis of the Strigolactone Mimic (+)-GR24,"A short and cost-effective synthesis of the important strigolactone analogue (+)-GR24 is described. Central to this new approach is the concise, enantioselective synthesis of the A-C ring system.",10.1021/jo402722p,2014-01-14,0.6354958949298551
Journal of Organic Chemistry,Total Synthesis of Zincophorin and Its Methyl Ester,"A total synthesis of the naturally occurring ionophore zincophorin has been realized. The route features an intramolecular oxymercuration of a cyclopropanemethanol and a Carroll-Claisen rearrangement for the respective elaboration of the C1-C12 and C13-C25 subunits, which have been assembled by using a highly diastereoselective titanium-mediated aldol condensation.",10.1021/jo0496042,2004-06-02,0.6354941191537626
Journal of the American Chemical Society,Total Synthesis of the Sesquiterpenoid Periconianone A Based on a Postulated Biogenesis,"The first enantioselective total synthesis of the complex tricarbocyclic sesquiterpenoid periconianone A based on a postulated biogenesis is reported. Key elements of the synthetic route include the use of an isopropenyl group as a removable directing group for stereoselective synthesis, a sequence featuring a Rh-mediated O-H insertion/[3,3]-sigmatropic rearrangement and subsequent α-ketol rearrangement, and a late stage aldol reaction to furnish the complex cage-like framework.",10.1021/jacs.7b10053,2017-10-27,0.6354925356315967
Angewandte Chemie International Edition,Total Synthesis of Azumamides A and E,"A zoom in on azumamides (2): An efficient synthetic route for two of the newly discovered marine natural products, namely azumamides A and E, has been developed (see picture). The present synthesis was followed by determination of the stereochemical structure of the azumamides.",10.1002/anie.200602033,2006-09-08,0.6354857337843899
Tetrahedron,Intramolecular cyclization of allylic propiolates mediated by the addition of stannyl radicals: A new synthetic route to α-methylene-γ-butyrolactones,,10.1016/s0040-4039(01)80626-2,1989-01-01,0.6354847752777159
Tetrahedron,The total synthesis of (±)-naphthyridinomycin. I. Preparation of a key tricyclic lactam intermediate.,,10.1016/s0040-4039(00)98338-2,1985-01-01,0.6354770651728763
Organic Process Research & Development,A Practical and Scalable Synthesis of a Glucokinase Activator via Diastereomeric Resolution and Palladium-Catalyzed C–N Coupling Reaction,"Here we describe the research and development of a process for the practical synthesis of glucokinase activator ( R )-1 as a potential drug for treating type-2 diabetes. The key intermediate, chiral α-arylpropionic acid ( R )-2, was synthesized in high diastereomeric excess through the diasteromeric resolution of 7 without the need for a chiral resolving agent. The counterpart 2-aminopyrazine derivative 3 was synthesized using a palladium-catalyzed C–N coupling reaction. This efficient process was demonstrated at the pilot scale and yielded 19.0 kg of ( R )-1 . Moreover, an epimerization process to obtain ( R )-7 from the undesired ( S )-7 was developed.",10.1021/acs.oprd.6b00415,2017-03-06,0.6354769891356608
Synthesis,Stereoselective Formal Synthesis of Herbarumin III via Prins Cyclization,"The total synthesis of herbarumin III is described, proving the versatility of the Prins cyclization in the synthesis of natural products. The approach is convergent and highly stereoselective. Ring-closing metathesis and alkene-rearrangement reactions are utilized as key steps in the synthesis of the macrolactone.",10.1055/s-0028-1083249,2008-12-01,0.6354655502205713
Synlett,"A Short Synthesis of (±)-Untenone A, a Marine Sponge Cyclopentenone","All articles of this category First synthesis of (±)-untenone A ( 1 ) has been achieved in five steps from ß-(phenylthio)acryloylsilane ( 3 ) and involves, as a key step, a [3 + 2] annulation of 3 with the lithium enolate of 2-octadecanone.",10.1055/s-1994-22783,1994-01-01,0.6354618559462565
Journal of Organic Chemistry,Total Synthesis of (±)-Hyphodermins A and D,"An efficient formal synthesis of (+/-)-hyphodermins A and D, metabolites of Hyphoderma radula, has been completed in 12 and 11 steps, respectively. The tricyclic carbon skeleton of enone 6 was rapidly assembled from diester 11 via an alpha brominationn-elimination sequence followed by anhydride formation. Regioselective reduction of the lactone group of enone 6 with LiAlH(t-BuO) 3 gave lactol 15. Lactol 15 was converted in two steps to (+/-)-hyphodermin D, without the need for complex protection-deprotection strategies. Lactol 15 was converted in three steps to (+/-)-hyphodermin A, via the key step of epoxidation of an enone in the presence of a THP lactol. A combination of NMR and ab initio studies suggests that the structures of hyphodermin C and D should be interchanged.",10.1021/jo800227p,2008-03-26,0.6354605328067272
Journal of the American Chemical Society,Synthesis of (−)-Morphine,The preparation of the diastereomerically pure beta-tetralone ketal 4 is reported. Intramolecular alkylidene C-H insertion followed by hydrolysis of 4 proceeded to give the enantiomerically pure cyclopentene 15. The key step in this synthesis was the bis-intramolecular cyclization of keto aldehyde 2 to give the tetracyclic intermediate 20. Enone 20 was converted over several steps to (-)-morphine 1.,10.1021/ja027882h,2002-09-28,0.6354484664427056
Organic Letters,Studies toward the Total Synthesis of Garsubellin A:  A Concise Synthesis of the 18-<i>epi</i>-Tricyclic Core,"[reaction: see text] During studies directed toward the total synthesis of garsubellin A, a concise stereocontrolled synthesis of the 18-epi-tricyclic compound 3 was achieved. Key steps were a one-pot stereoselective construction of the bicyclic lactone 23 followed by a formal migration to the bicyclo[3.3.1]nonane-1,3,5-trione and an intramolecular Wacker-type tetrahydrofuran ring formation.",10.1021/ol0255965,2002-02-08,0.6354346563572393
Tetrahedron,Synthetic studies on arene-olepin cycloadditions-VII:1 a three-step total synthesis of (±)-silphinene,,10.1016/s0040-4039(00)98120-6,1985-01-01,0.6354329739460363
Synlett,"Novel Methodology for the Efficient Synthesis of 3-Aryloxindoles: [1,2]-Phospha-Brook Rearrangement–Palladium-Catalyzed Cross-Coupling Sequence","A novel methodology for the efficient synthesis of 3-aryloxindoles from isatin derivatives was developed. The methodology involves the formation of an oxindole having a phosphate moiety at the C-3 position via the [1,2]-phospha-Brook rearrangement under Brønsted base catalysis followed by palladium-catalyzed cross-coupling with aryl boron reagents. The one-pot synthesis of 3-aryloxindoles from isatin derivatives is also described.",10.1055/s-0035-1561859,2016-04-07,0.6354272593413406
Journal of Organic Chemistry,"Total Synthesis of (−)-Mniopetal E, a Novel Biologically Intriguing Drimane Sesquiterpenoid","We have achieved the total synthesis of (-)-mniopetal E, a drimane sesquiterpenoid which inhibits the reverse transcriptase of human immunodeficiency virus (HIV)-1. Our enantiospecific total synthesis of this target molecule in naturally occurring form commenced with a known 2,3-anhydro-D-arabinitol derivative, which was prepared using the Sharpless asymmetric epoxidation strategy. The key steps of our total synthesis were as follows: (1) a combination of highly stereocontrolled inter- and intramolecular Horner-Emmons carbon elongations for construction of a butenolide tethering a 1,2,4, 9-functionalized nona-5,7-diene moiety at the beta-carbon, (2) stereoselective thermal intramolecular Diels-Alder reaction of the thus-formed trienic compound, providing preferentially an endo-cycloadduct with the desired pi-facial selection, and (3) efficient transformation of the gamma-lactone moiety in the major cycloadduct to the gamma-hydroxy-gamma-lactone part in mniopetal E. Our total synthesis of (-)-mniopetal E established the unsettled absolute stereochemistry of the antibiotic.",10.1021/jo001004p,2000-11-11,0.6354130547284644
Organic Letters,Stereochemical Reassignment by Total Synthesis of an Ocular Pyridinium Bisretinoid of Retinal Pigment Epithelium Lipofuscin: <i>iiso</i> -A2E Is <i>i</i> -A2E,"The stereoselective synthesis of recently discovered lipofuscin fluorophore iiso -A2E, a C3,C4-bis-polyenylpyridinium salt derived from all- trans -retinal, which has been detected in human, pig, mouse, and bovine eyes, has been completed. The Suzuki–Miyaura cross-coupling reaction and Horner–Wadsworth–Emmons condensation were the key synthetic steps for the construction of the tetraenyl and pentaenyl arms, respectively, starting from a properly functionalized pyridine-3,4-dialdehyde surrogate, followed by pyridine alkylation. Subtle changes in the 1 H NMR and 13 C NMR spectra of the synthetic compound and natural compound suggested the structural revision of the latter, for which the C13′═C14′ E isomer at the longer C3-unsaturated pentaenyl chain of the pyridinium ring was proposed. The synthesis confirmed the alternative stereostructure of the natural pigment, which should be named i -A2E, thus correcting the double bond geometry of the natural fluorophore at C13′═C14′.",10.1021/acs.orglett.5c04694,2025-12-04,0.6354087935540567
Tetrahedron,Synthesis of 2-nitroindoles via the Sundberg indole synthesis,"A three-step sequence has been developed for converting o-nitrobenzaldehydes into 2-nitroindoles. The key step involves the thermolysis of 2-(o-azidophenyl)nitroethylene (10) in xylenes which gives 2-nitroindole (4) in 54% yield, akin to the classic Sundberg indole synthesis. This procedure has also been utilized to synthesize 5,6-dimethoxy-2-nitroindole (14).",10.1016/s0040-4039(97)01272-0,1997-08-01,0.6353666564184002
Synthesis,"A Convenient Synthesis of 3-Chloro-3,4-dihydro-4-hydroxy-3-nitro-2-phenyl-2<i>H</i>-1-benzopyrans",All articles of this category The novel title compounds 5 are prepared by a simple and efficient two-step procedure starting from substituted benzaldehydes 1 . A convenient route to the (2-chloro-2-nitroethenyl)benzenes 3 required as intermediates in the synthesis is reported.,10.1055/s-1990-26791,1990-01-01,0.635363029722509
Organic Letters,Convergent Synthesis of the HIJKLM Ring System of Ciguatoxin CTX3C,"The HIJKLM ring system of ciguatoxin CTX3C was synthesized in a convergent manner. The key steps were a conjugate addition/alkylation sequence, spiroacetalization, intramolecular allylation, ring-closing metathesis, and hydrogenation to form the 36-α-methyl substituent.",10.1021/ol2019136,2011-08-01,0.6353519867922723
Synlett,Concise Diastereoselective Total Synthesis of (±)-Parvistemonine A,"Abstract We have developed a concise diastereoselective total synthesis of (±)-parvistemonine A. By using a Mukaiyama–Michael addition, an aza-Wittig reaction, a Paal–Knorr pyrrole synthesis, an acid-mediated annulation, and a Mitsunobu reaction as key steps, we achieved a total synthesis in which the longest linear sequence was ten steps and the overall yield was 19.6%. Additionally, the relative stereochemistry of parvistemonine A was confirmed by X-ray crystallographic analysis for the first time.",10.1055/s-0040-1707283,2020-09-18,0.6353455501587689
European Journal of Organic Chemistry,A Short and Efficient Approach for the Total Synthesis of (<i>S</i>)‐Zearalenone and (<i>R</i>)‐De‐<i>O</i>‐methyllasiodiplodin by Using Stille and RCM Protocols,"Abstract A concise, flexible, and linear approach has been devised for the total synthesis of the resorcinylic acid lactones ( S )‐zearalenone ( 2 ) and ( R )‐de‐ O ‐methyllasiodiplodin ( 4 ) by using a Stille cross‐coupling strategy. The other key steps of the synthesis include a ring‐closing metathesis (RCM), a chemoselective reduction of an α,β‐unsaturated ketone, and a transesterification reaction.",10.1002/ejoc.201501545,2016-02-23,0.6353454932096018
Journal of Organic Chemistry,"The Total Synthesis of Retrojusticidin B, Justicidin E, and Helioxanthin","Making use of a tandem free radical cyclization process mediated by Mn(OAc)3 as a key operation, the total synthesis of retrojusticidin B, justicidin E, and helioxanthin has been concisely achieved in four or five steps in an overall yield of 45, 33 and 44%, respectively, from a common starting material 5.",10.1021/acs.joc.5b00866,2015-06-05,0.6353409028856616
Journal of Organic Chemistry,An <i>N</i>-Acyliminium Cyclization Approach to a Total Synthesis of (+)-Cylindricine C,"[reaction: see text] Details of problems and solutions encountered during the development of an enantioselective total synthesis of (+)-cylindricine C are described here. The total synthesis itself was accomplished in 8 steps, featuring an N-acyliminium cyclization strategy, the seldom-used Wharton rearrangement, and a key epimerization at C5.",10.1021/jo0501846,2005-04-09,0.6353400012621845
Journal of Organic Chemistry,A Short Synthetic Route to the Calystegine Alkaloids,"An efficient strategy is described for the synthesis of enantiopure calystegine alkaloids. The key step employs a zinc-mediated fragmentation of benzyl-protected methyl 6-iodo-glycosides followed by in situ formation of the benzyl imine and Barbier-type allylation with zinc, magnesium, or indium metal. Stereochemistry in the pivotal allylation is controlled by the choice of the metal. The functionalized 1,8-nonadienes, thus formed, are converted into cycloheptenes by ring-closing olefin metathesis. Regioselective hydroboration and oxidation give the corresponding cycloheptanones, which are deprotected to afford the desired calystegines. Hereby, calystegine B(2), B(3), and B(4) are prepared from D-glucose, D-galactose, and D-mannose, respectively. This route constitutes the shortest synthesis of calystegine B(2) and gives rise to the first total syntheses of calystegine B(3) and B(4).",10.1021/jo020645c,2003-02-15,0.6353310540429749
Tetrahedron,A new expeditious synthesis of (+)-exo-brevicomin via efficient CC bond formation of triflates,,10.1016/s0040-4039(00)99305-5,1989-01-01,0.6353289500273839
Synlett,"Synthesis of 1α, 25-Dihydroxyvitamin D<sub>3</sub> A-Ring Synthon by Pd-Catalyzed Cyclization","All articles of this category A short and efficient synthesis of 1α, 25-dihydroxyvitamin D 3 A-ring synthon starting from diketene, acrolein and ethyl malonate by using palladium-catalyzed cyclization of the ( Z )-enol triflate is described. Heck reaction - Vitamin D 3 - cyclization",10.1055/s-1997-745,1997-02-01,0.6353205017518189
Journal of Organic Chemistry,Formal Synthesis of Optically Active Ingenol via Ring-Closing Olefin Metathesis,"The construction of strained carbon skeletons by ring-closing olefin metathesis (RCM) was investigated. With well-designed diene 4, RCM was found to be applicable to the formation of a highly strained inside-outside bicyclo[4.4.1]undecane skeleton of ingenol, a bioactive diterpenoid, and formal total synthesis of optically active ingenol (1) was achieved. The key features of this synthesis are construction of an A-ring by spirocyclization of the ketone with an allylic chloride unit, 26, and ring closure of a B-ring by olefin metathesis. Starting from Funk's keto ester 6, the key intermediate aldehyde 9 in Winkler's total synthesis was synthesized in eight steps in 12.5% overall yield. This strategy of direct cyclization of a strained inside-outside skeleton provided the first easy access to optically active ingenol.",10.1021/jo048833l,2004-10-13,0.6353171315358956
Journal of the American Chemical Society,Enantioselective Total Synthesis of (+)-Heilonine,"High Resolution Image Download MS PowerPoint Slide Chemical transformations that rapidly and efficiently construct a high level of molecular complexity in a single step are perhaps the most valuable in total synthesis. Among such transformations is the transition metal catalyzed [2 + 2 + 2] cycloisomerization reaction, which forges three new C–C bonds and one or more rings in a single synthetic operation. We report here a strategy that leverages this transformation to open de novo access to the Veratrum family of alkaloids. The highly convergent approach described herein includes (i) the enantioselective synthesis of a diyne fragment containing the steroidal A/B rings, (ii) the asymmetric synthesis of a propargyl-substituted piperidinone (F ring) unit, (iii) the high-yielding union of the above fragments, and (iv) the intramolecular [2 + 2 + 2] cycloisomerization reaction of the resulting carbon framework to construct in a single step the remaining three rings (C/D/E) of the hexacyclic cevanine skeleton. Efficient late-stage maneuvers culminated in the first total synthesis of heilonine ( 1 ), achieved in 21 steps starting from ethyl vinyl ketone.",10.1021/jacs.1c08756,2021-09-29,0.6353045670685216
Journal of Organic Chemistry,"Total Synthesis of Polycavernosides A and B, Two Lethal Toxins from Red Alga","Polycavernosides A and B are glycosidic macrolide natural products isolated as the toxins causing fatal human poisoning by the edible red alga Gracilaria edulis (Polycavernosa tsudai). Total synthesis of polycavernosides A and B has been achieved via a convergent approach. The synthesis of the macrolactone core structure is highlighted by the catalytic asymmetric syntheses of the two key fragments using hetero-Diels-Alder reaction and Kiyooka aldol reaction as the key steps, their union through Suzuki-Miyaura coupling, and Keck macrolactonization. Finally, glycosylation with the l-fucosyl-d-xylose unit and construction of the polyene side chain through Stille coupling completed the total synthesis of polycavernosides A and B.",10.1021/acs.joc.7b02293,2017-11-10,0.6352986393635991
Organic Letters,Total Synthesis of (±)-Anigorootin,"An 11-step synthesis of the octacyclic-fused dimeric phenylphenalenone anigorootin (phytoalexin in banana plants) is reported. The synthetic strategy uses an electrochemical dimerization as the key step, which stereospecifically installs the four asymmetric centers. Mechanistic aspects of the dimerization process are discussed.",10.1021/acs.orglett.4c03090,2024-10-09,0.6352885867598729
Angewandte Chemie International Edition,Total Synthesis of Cochlearol B via Intramolecular [2+2] Photocycloaddition,"Herein, we describe the first total synthesis of cochlearol B, a meroterpenoid natural product featuring a 4/5/6/6/6-fused pentacyclic structure. Key steps, oxidative cyclization and subsequent intramolecular [2+2] photocycloaddition, which constructed the pentacyclic structure in highly stereoselective manner, allowed efficient access to cochlearol B with the longest linear sequence of 16 steps, and in 9 % overall yield. Single-crystal X-ray crystallographic analysis clearly confirmed the stereochemistry of cochlearol B.",10.1002/anie.202110556,2021-09-17,0.6352792060352254
Synlett,Preparation of an Advanced Phenylglycine-Derived Intermediate<i>en route</i>to the Southern Hemisphere Tetraene of Viridenomycin,"A high-yielding synthesis of a phenylglycine derived (E,Z)-dienylboronate en route to the C16-C23 tetraene of the polyene macrolide viridenomycin is described. Crucial to this synthesis was the development of conditions enabling ready access to synthetically useful amino acid derivatives that should be widely applicable to other amino acids. These conditions confer advantages of increased yield and reliability over many of the existing literature alternatives, and also circumvent several of the problems encountered when dealing with such derivatives. The synthesis features a highly selective Heck coupling between an N-protected (Z)-alkenyl iodide and a hexylene glycol derived vinylboronate ester.",10.1055/s-2004-825582,2004-01-01,0.6352632187202962
Organic Process Research & Development,A Practical Synthesis of the Dual Matrix Metalloprotease/Tumor Necrosis Factor Inhibitor MMP090,"A practical 9-step synthesis of the dual matrix metalloprotease/tumor necrosis factor inhibitor MMP090, trans -( R )-[[ N -(4-ethoxyphenylsulfonyl)- N -(4-pyridinylmethyl)]amino]- N -hydroxy-4-propoxy cyclohexaneacetamide 10, was accomplished in 12% overall yield from d -4-hydroxyphenylglycine. Highlights include: (1) selective hydrogenation of d -hydroxyphenylglycine to afford predominantly the trans isomer without racemization; (2) virtually complete removal of the undesired cis diastereoisomer by fractional recrystallization of a TBS ether derivative of the functionalized cyclohexylglycine; (3) direct conversion of the TBS ether into the n -propyl ether in the presence of a catalytic amount of bismuth bromide in high yield; and (4) conversion of the carboxylic acid into the hydroxamic acid using an aqueous solution of hydroxylamine.",10.1021/op050066k,2005-08-27,0.6352604719912187
Organic Letters,Synthesis of Sceptrin Alkaloids,[reaction: see text] A concise synthetic route to the marine alkaloids (+/-)-sceptrin and (+/-)-dibromosceptrin has been developed.,10.1021/ol049283g,2004-06-18,0.6352399665441234
Organic Process Research & Development,Development of Scalable Conditions for the Ugi Reaction—Application to the Synthesis of (<i>R</i>)-Lacosamide,"The Ugi reaction is applied for the preparation of ( R )-lacosamide, an important drug for the treatment of epilepsy. To this end, key issues associated with the Ugi reaction, such as a practical preparation of the foul-smelling isocyanide as well as the efficient introduction of chirality via a cheap and easily removable chiral directing group, were solved. Enantiomerically pure (>99.9% ee) drug substance meeting all required purity specifications is prepared in operationally simple four steps in 40% overall yield from the commodity chemical benzylamine.",10.1021/acs.oprd.5b00228,2015-10-12,0.6352357408736456
Organic Letters,Total Synthesis of Sarpagine Alkaloid (−)-Normacusine B,"An asymmetric total synthesis of the sarpagine alkaloid (-)-normacusine B is presented. Salient features of this synthesis include a photocatalytic nitrogen-centered radical cascade reaction to assemble the tetrahydrocarbolinone skeleton, a titanium-mediated intramolecular amide-alkene coupling to construct the bridged azabicyclo[3.3.1]nonane moiety, and a nickel-catalyzed reductive Heck coupling to assemble the azabicyclo[2.2.2]octane ring system.",10.1021/acs.orglett.2c01177,2022-05-11,0.6352346112768326
Tetrahedron,‘One-pot’ four-step synthesis of cerpegin,,10.1016/j.tetlet.2005.03.176,2005-04-16,0.6352338096194913
Organic Process Research & Development,Routes for the Synthesis of (2<i>S</i>)-2-Methyltetrahydropyran-4-one from Simple Optically Pure Building Blocks,"Routes to (2 S )-2-methyltetrahydropyran-4-one of high optical purity starting from readily available chiral pool precursors and suitable for large-scale manufacture are described. In one approach, the key step is cyclisation of ( S )-5-hydroxyhex-1-en-3-one, derived either from an alkyl ( S )-3-hydroxybutyrate or ( S )-propylene oxide. Formation of the tetrahydropyran ring directly via an intramolecular oxy-Michael reaction under acid-catalysed conditions resulted in loss of optical purity, whereas proceeding through the intermediate (2 S )-2-methyl-2,3-dihydropyran-4-one, via an oxidative Pd-catalysed ring closure, followed by hydrogenation of the alkenyl bond, preserved the optical purity. An alternative approach to (2 S )-2-methyl-2,3-dihydropyran-4-one is also reported, again starting from an alkyl ( S )-3-hydroxybutyrate by elaboration to a carbonyl-protected (6 S )-6-methyl-5,6-dihydropyran-2,4-dione derivative, followed by partial reduction and dehydration. Alternatively, the carbonyl group can be reduced out completely in one step to furnish (2 S )-2-methyltetrahydropyran-4-one directly after deprotection.",10.1021/op900163a,2009-12-03,0.6352315852291843
Tetrahedron,"A highly flexible route to tricyclo[4.3.1.03.7]-, and tricyclo[4.3.0.04,10]decanes A short synthesis of pupukean-2-one",,10.1016/s0040-4039(98)80053-1,1999-01-01,0.6352295927279908
Organic Process Research & Development,"Industrial Application of the Forster Reaction: Novel One-Pot Synthesis of Cinacalcet Hydrochloride, a Calcimimetic Agent","Described is a new, practical, and one-pot process, based on the Forster reaction, for the synthesis of cinacalcet hydrochloride ( 1 ), a calcimimetic agent and calcium-sensing receptor antagonist. The synthesis comprises the condensation of (1 R )-(+)-1-naphthylethyl amine ( 2 ) with benzaldehyde ( 3 ) followed by reaction of obtained Schiff’s base 4 with 1-(3-halopropyl)-3-(trifluoromethyl)benzene ( 5 ) to provide highly unstable iminium salt 6 . Subsequent hydrolysis of 6 with water in the same pot yielded cinacalcet. The treatment of cinacalcet with hydrochloric acid during the workup process furnished 1 with an overall yield of around 60%. Our synthetic approach for 1, discussed in this report demonstrates industrial application of the century-old, unexplored name reaction, “Forster’s Reaction” or Forster−Decker synthesis.",10.1021/op200016a,2011-02-24,0.6352235997738831
Journal of Organic Chemistry,"A Short and Convenient Chemical Route to Optically Pure 2-Methyl Chromanmethanols. Total Asymmetric Synthesis of β-, γ-, and δ-Tocotrienols","With use of inexpensive commercially available raw materials, chromanmethanol precursors to the natural beta-, gamma-, and delta-tocotrienols have been prepared in high yield. Enzymatic resolution afforded chiral chromanmethanols in high enantiomeric excess. Subsequent attachment of the farnesyl side chain was high yielding, thus allowing the preparation of asymmetric beta-, gamma-, and delta-tocotrienols in one final step wherein simultaneous deprotection of the phenol and removal of the sulfone group occurs. This chemistry provides the first synthesis of natural-series beta-tocotrienol.",10.1021/jo0705418,2007-08-09,0.6352177092882875
Organic Process Research & Development,Synthesis of an α-Amylase Inhibitor: Highly Stereoselective Glycosidation and Regioselective Manipulations of Hydroxyl Groups in Carbohydrate Derivatives,"Here, we describe the efficient synthesis of α-amylase inhibitor 1 . To introduce the most expensive C ring unit at a late stage in the synthesis, we developed 1,2- cis - O -glycosidation of AB and C ring intermediates. Taking advantage of the effect of non-neighboring protecting groups, reaction solvents, and temperature for the glycosidation led to high stereoselectivity and high yield of the 1,2- cis -glycoside product bearing the API skeleton. We also explored protection and deprotection methods for regioselective manipulation of hydroxyl groups in A and B ring intermediates. One-pot benzylation of the 2,3-hydroxyl groups of d -glucose under phase-transfer conditions and regioselective anomeric deacetylation with N -methylpiperazine were developed for the syntheses of A, B, and AB ring intermediates. Thus, the efficiency of the process was dramatically improved. The raw material cost of API was reduced to approximately one-third that of the original route, and the total process was decreased by six steps.",10.1021/op500306p,2014-11-14,0.6352111466963368
Synlett,Enantioselective Annulation Using Nazarov Reagent: Synthesis of (+)-Preoleanatetraene,The enantioselective synthesis of preoleanatetraene (1) has been accomplished via a convergent approach of two C-15 synthons. The key step of this synthesis has been an interesting enantio­selective variant of the Robinson annulation using the Nazarov reagent and a chiral enamine to obtain the bicyclic moiety A. This asymmetric methodology opens the access to other irregular triterpene skeletons whose biogenetic implication should not be underestimated.,10.1055/s-2005-864798,2005-01-01,0.6351971429665142
Organic Process Research & Development,Development of a Practical and Scalable Synthesis of (<i>R</i>)- and (<i>S</i>)-3-Amino-2-[(benzyloxy)methyl]propan-1-ol Monohydrochloride: A Useful C-4 Chiral Building Block,"The development of a practical and scalable synthesis of a C-4 chiral amine building block ( R ) - 1·HCl and ( S ) - 1·HCl is described. This important chiral intermediate ( R ) - 1·HCl is efficiently synthesized from the commercially available, inexpensive, and simple 2-(hydroxymethyl)-1,3-propanediol ( 31 ) using lipase-catalyzed enantioselective hydrolysis as a key reaction. Development resulted in a telescoped process that was operated successfully and reproducibly in a pilot-plant-scale synthesis, and 22 kg of chiral amine ( R ) - 1·HCl was prepared in the first scale-up synthesis. This synthetic method is also useful for preparation of the important chiral building block ( S ) - 1·HCl, which is the enantiomer of ( R ) - 1·HCl .",10.1021/op3001383,2012-08-15,0.6351813014286065
Organic Letters,"Estrogen Receptor Ligands. 12. Synthesis of the Major Metabolites of an ERα-Selective, Dihydrobenzoxathiin Antagonist for Osteoporosis","[reaction: see text] During the course of drug metabolism studies, a major metabolite of compound 1 was detected in rhesus monkeys and assigned structure 4. The intriguing biotransformation of 1 leading to 4 was confirmed by a 19-step total synthesis starting from resorcinol (11), the key feature of which was the construction of the oxygen bridge utilizing a phenolic oxidation and trapping sequence. In addition, the synthesis of a related metabolite (5) is described.",10.1021/ol047741f,2005-01-05,0.6351749421823647
Journal of the American Chemical Society,Total Syntheses of Ipomoeassin B and E,"A concise, flexible, and efficient total synthesis of the cytotoxic resin glycosides ipomoeassin B ( 1 ) and ipomoeassin E ( 2 ) is reported which features the advantages of a novel protecting group strategy employing ( Z )-3-dimethyl(phenyl)silyl-2-propenoic acid as cinnamic acid surrogate. The use of this readily available compound allowed the macrocycle of the glycolipids to be formed by ring closing olefin metathesis (RCM) with the aid of the second generation Grubbs carbene complex 12 . The resulting E/Z mixture could be selectively hydrogenated using Wilkinson's catalyst [RhCl(PPh 3 ) 3 ] without affecting the unsaturated esters in the periphery of the compound, before the C-silyl group was cleaved off with TASF [tris(dimethylamino)sulfonium difluorotrimethylsilicate] under notably mild conditions to release the required cinnamate moiety. Other key steps of the synthesis route comprise the formation of the disaccharide linkage by the trichloroacetimidate method, the formation of the chiral acid segment 19 via a VO(acac) 2 -catalyzed, tert -BuOOH-induced oxidative rearrangement of the optically pure furyl alcohol (−)- 15 (Achmatowicz-type reaction), and a reductive cleavage of the 4,6- O - p -methoxybenzylidene acetal in 5 with NaBH 3 CN and Me 3 SiCl (TMSCl), the regiochemical course of which was found to be opposite to that previously reported in the literature for sterically less encumbered substrates.",10.1021/ja068901g,2007-01-25,0.6351748499785937
Organic Process Research & Development,"Improved Process for the Preparation of Montelukast: Development of an Efficient Synthesis, Identification of Critical Impurities and Degradants","An improved and scalable process for the production of montelukast (Singulair, drug for asthma) based on a new and advantageous method of carrying out the key substitution reaction has been developed. The present procedure is distinguished from the previous solutions in the use of linear or cyclic polyethers, which ensures higher selectivity of the key step. The improved process for the preparation of montelukast is able to minimize a content of impurities and allows the effective production of montelukast and its scale-up.",10.1021/op900311z,2010-02-11,0.6351745656192797
Tetrahedron,"A practical and efficient route for synthesis of 6-aminomethyl-4-oxo-4,5,6,7-tetrahydroindoles as new CNS agent precursors",,10.1016/0040-4039(96)01028-3,1996-07-01,0.6351598664062987
Journal of Organic Chemistry,Synthesis of Trideca-<i>O</i>-methyl-α-pedunculagin. Diastereo-Favoritism Studies on Intramolecular Ester-Cyclization of Axially Chiral Diphenic Acids with Carbohydrate Core,"Total synthesis of trideca-O-methyl-alpha-pedunculagin was achieved by a simple sequence. The key step is the synthesis of methyl 4,6-O-benzylidene-2,3-O-[(S)-4,4',5,5',6,6'-hexamethoxydiphenoyl]-alpha-D-glucopyranoside through intramolecular ester-cyclization of racemic hexamethoxydiphenoyl chloride with methyl 4,6-O-benzylidene-alpha-D-glucopyranoside at the 2,3-position. The diastereoselectivity results obtained in the intramolecular cyclization of hexamethoxydiphenic acid to the carbohydrate core raises a very interesting point in considering the pathway of (R)-diphenic acid biosynthesis.",10.1021/jo950969j,1996-01-01,0.6351480763889564
Angewandte Chemie International Edition,"Concise Total Synthesis of (−)‐Calycanthine, (+)‐Chimonanthine, and (+)‐Folicanthine","Conjoined twins: An efficient and convergent strategy for the synthesis of the dimeric hexahydropyrroloindole alkaloids, (+)-chimonanthine, (+)-folicanthine, and (−)-calycanthine, is described. The simultaneous formation of the vicinal quaternary stereocenters by using a reductive dimerization reaction provides an access to the optically active key intermediate on a gram scale.",10.1002/anie.200700705,2007-04-05,0.6351467344364288
Journal of Organic Chemistry,"Synthesis of Substituted 2,3-Benzodiazepines","A new, four-step synthetic route for substituted 2,3-benzodiazepines 1, starting from aldehyde 4, was developed with excellent overall yields. This route included the 1,2-addition of various aromatic Grignard reagents to 4, PCC oxidation, and aerobic Wacker-type oxidation of the olefinic group of 6, followed by condensation of the resulting 1,5-dicarbonyl 7 with N 2 H 4 . Isoquinolones 9 were obtained when an aldehyde group was used instead of a ketone. The key structures were confirmed by X-ray single-crystal diffraction analysis.",10.1021/acs.joc.6b01935,2016-10-07,0.6351433663984283
Organic Letters,"Asymmetric Hydrogenation of β-Azaaryl α,β-Unsaturated Nitriles: An Access to Ruxolitinib","An enantioselective hydrogenation of β-azaaryl α,β-unsaturated nitriles catalyzed by a rhodium/( S C,R p )- N -Me-ZhaoPhos complex has been developed, offering an efficient and highly stereoselective route for the asymmetric synthesis of ruxolitinib (>99% yield, 99% ee). A wide range of α,β-unsaturated nitriles were hydrogenated to the corresponding products with excellent enantioselectivities (up to 99% ee). This methodology provides a versatile and practical approach to accessing bioactive chiral nitriles, including key intermediates for pharmaceuticals such as ruxolitinib precursors.",10.1021/acs.orglett.5c01468,2025-05-12,0.6351424515457311
Synlett,"Straightforward and EfficientSynthesis of (4<i>R</i>,6<i>S</i>)-4-(<i>tert</i>-Butyldimethylsiloxy)-6-(hydroxymethyl)tetrahydropyran-2-one","A novel synthetic approach to (4R,6S)-4-(tert-butyldi­methylsiloxy)-6-(hydroxymethyl)tetrahydropyran-2-one, a key precursor of statin side chain, is described. A prime feature of the presented strategy is the transformation of (4R,6S)-4-(tert-butyldimethylsiloxy)-6-(iodomethyl)tetrahydropyran-2-one to an acetate ester derivative and subsequent cleavage of an acetate protection by applying homogeneous tin catalysis. Iodolactone used in the study is accessible by a new route in five steps from (S)-ethyl 4-chloro-3-hydroxybutanoate. This method overcomes many of the drawbacks associated with previously reported approaches. It gives the title compound in 21% over seven steps, which is the highest attained overall yield yet. The disclosed approach was realized in convenient and economical manner suitable for industrial use.",10.1055/s-2008-1077957,2008-07-15,0.6351360958330515
Journal of the American Chemical Society,Asymmetric Total Synthesis of (−)-Phaeocaulisin A,"High Resolution Image Download MS PowerPoint Slide The therapeutic properties of Curcuma (ginger and turmeric’s family) have long been known in traditional medicine. However, only recently have guaiane-type sesquiterpenes extracted from Curcuma phaeocaulis been submitted to biological testing, and their enhanced bioactivity was highlighted. Among these compounds, phaeocaulisin A has shown remarkable anti-inflammatory and anticancer activity, which appears to be tied to the unique bridged acetal moiety embedded in its tetracyclic framework. Prompted by the promising biological profile of phaeocaulisin A and by the absence of a synthetic route for its provision, we have implemented the first enantioselective total synthesis of phaeocaulisin A in 17 steps with 2% overall yield. Our route design builds on the identification of an enantioenriched lactone intermediate, tailored with both a ketone moiety and a conjugated alkene system. Taking advantage of the umpolung carbonyl-olefin coupling reactivity enabled by the archetypal single-electron transfer (SET) reductant samarium diiodide (SmI 2 ), the lactone intermediate was submitted to two sequential SmI 2 -mediated cyclizations to stereoselectively construct the polycyclic core of the natural product. Crucially, by exploiting the innate inner-sphere nature of carbonyl reduction using SmI 2, we have used a steric blocking strategy to render sites SET-unreceptive and thus achieve chemoselective reduction in a complex substrate. Our asymmetric route enabled elucidation of the naturally occurring isomer of phaeocaulisin A and provides a synthetic platform to access other guaiane-type sesquiterpenes from C. phaeocaulis ─as well as their synthetic derivatives─for medicinal chemistry and drug design.",10.1021/jacs.2c02188,2022-04-13,0.6351282159226985
Tetrahedron,An efficient asymmetric hydrogenation approach to the synthesis of the Crixivan® piperazine intermediate,,10.1016/s0040-4039(98)01484-1,1998-09-01,0.635111302366714
Journal of Organic Chemistry,Convergent Synthesis of a β-(1→3)-Mannohexaose,An as yet unknown beta-(1-->3)-mannohexaose has been synthesized by a block route involving the coupling of two trisaccharides. Comparison of three closely related attempted mannohexaose syntheses reinforces the influence of subtle matching and/or mismatching interactions on the outcome of convergent oligosaccharide synthesis.,10.1021/jo071009n,2007-08-01,0.6351109518665786
Angewandte Chemie International Edition,Total Synthesis of (±)‐Symbioimine,"An inside job: A Lewis acid induced intramolecular Diels–Alder (IMDA) reaction is used as the key step in the formation of symbioimine, an iminium alkaloid. The intermediate octahydronaphthalene is obtained from the IMDA reaction, after which extension of the aldehyde to a nitrile, alkylation of the nitrile, and imine formation allows for an efficient route to the target compound (see scheme; TBS=tert-butyldimethylsilyl).",10.1002/anie.200601418,2006-06-27,0.6351066296855792
Organic Process Research & Development,Stereoselective Process for a CCR3 Antagonist,"A convergent, multikilogram, stereoselective synthesis of 1 is described. A key fragment, ( S )-3-(4-fluorobenzyl)piperidine ( 2 ) was synthesized from valerolactam in three steps using our recently discovered Ir−BDPP-catalyzed asymmetric hydrogenation. Another key fragment, (1 R,2 R )-2-(benzyloxycarbonylamino)cyclohexanecarboxaldehyde ( 3 ) was synthesized from meso -hexahydrophthalic anhydride in seven steps. The stereochemistry was set in the first step of this sequence via a quinidine-mediated desymmetrization of the meso -anhydride. Coupling of the fragments 2 and 3 followed by deprotection provided the penultimate 23 . The active pharmaceutical ingredient (API) free base 1 was obtained by treatment of 23 with the aminothiazole fragment 4 under mild conditions.",10.1021/op050202l,2006-01-12,0.6351059905458983
Journal of Organic Chemistry,Synthesis of the ABC Ring of Calyciphylline A-Type Alkaloids by a Stereocontrolled Aldol Cyclization: Formal Synthesis of (±)-Himalensine A,"High Resolution Image Download MS PowerPoint Slide A synthetic approach to a functionalized ABC-tricyclic framework of calyciphilline A-type alkaloids, a building block toward this class of alkaloids, is reported. The key synthetic steps involve a radical cyclization to form the hydroindole system and piperidine ring closure through a stereocontrolled aldol cyclization. The resulting alcohol allows the methyl group to be installed in the bowl-shaped azatricyclic structure; this crucial reaction takes place with configuration retention. The synthesis of azatricyclic compound I constitutes a formal synthesis of himalensine A.",10.1021/acs.joc.2c01171,2022-07-21,0.6351049999846046
Synlett,"A Short Efficient Route to C<sub>2</sub>Symmetric 1,1′,2,2′-Tetrasubstituted Ferrocenes","All articles of this category The C 2 symmetric bis -phosphinoferrocene ( 3 ), has been prepared in 52% overall yield from ferrocene by a sequence involving controlled lithiations of the ferrocene rings.",10.1055/s-1994-34977,1994-01-01,0.6351001553341409
Tetrahedron,"exo-N-[2-(4-Azido-2,3,5,6-tetrafluorobenzamido)ethyl]-dC: a novel intermediate in the synthesis of dCTP derivatives for photoaffinity labelling",,10.1016/j.tetlet.2007.12.083,2007-12-28,0.6350955099169019
Tetrahedron,Organocatalytic asymmetric 5-hydroxypyrrolidine synthesis: a highly enantioselective route to 3-substituted proline derivatives,,10.1016/j.tetlet.2007.10.028,2007-10-11,0.635095417075211
Tetrahedron,"Synthesis of oxidative metabolites of K-115, a novel Rho-kinase inhibitor",,10.1016/j.tetlet.2021.153589,2021-12-15,0.6350875783711782
Organic Letters,An Effective Enantioselective Approach to the Securinega Alkaloids:  Total Synthesis of (−)-Norsecurinine,"[reaction: see text] A highly versatile approach to the enantioselective synthesis of securinega alkaloids is presented. Crucial steps are a palladium-catalyzed enantioselective imide alkylation, a vinylogous Mannich reaction, and a ring-closing metathesis process. Through this strategy, the synthesis of (-)-norsecurinine has been accomplished in nine steps and 11% overall yield.",10.1021/ol0522079,2005-10-01,0.6350791170595322
Journal of the American Chemical Society,(+)-Saxitoxin:  A First and Second Generation Stereoselective Synthesis,"A stereoselective synthesis of the bis-guanidinium toxin (+)-saxitoxin (STX), the agent infamously associated with red tides and paralytic shellfish poisoning, is described. Our approach to this unique natural product advances through an unusual nine-membered ring guanidine intermediate 39 en route to the tricyclic skeleton that defines STX. The effectiveness of this strategy is notable, as only four steps are needed to transform 39 into the target molecule, including a four-electron alkene oxidation catalyzed by OsCl3. Construction of the critical monocyclic guanidine has been achieved through two channels, the first of which makes use of Rh-catalyzed C-H amination and highlights a novel class of heterocyclic N,O-acetals as iminium ion equivalents for crafting functionalized amines. A second route to 39 relies on a stereoselective acetylide dianion addition to a serine-based nitrone, thereby facilitating the preparation of STX in just 14 linear steps from commercial material.",10.1021/ja071501o,2007-07-21,0.6350732313621305
Synlett,"Synthesis of Aplyolide A, Ichthyotoxic Macrolide Isolated from the Skin of the Marine Mollusk Aplysia depilans",All articles of this category A convergent pathway is described for the synthesis of ( S )-aplyolide A ( 1 ) using ethyl ( S )-lactate as chiral source. Key steps of the synthesis are two couplings between copper(I) alkynides and propargylic halides for the formation of skipped diyne systems and were performed with an improved procedure based on the use of cesium carbonate as base for alkynide preparation. aplyolide A - natural product - macrocycles - total synthesis - alkynes,10.1055/s-2001-18749,2001-01-01,0.6350688869889186
Journal of the American Chemical Society,Chiral Crotylsilane-Based Approach to Benzoquinoid Ansamycins:  Total Synthesis of (+)-Macbecin I,"A highly convergent total synthesis of the antitumor antibiotic (+)-macbecin I ( 1 ) has been achieved through the homologation of the aldehyde 3 (C5−C21 aromatic fragment) to the E,Z -dienoate 2 by employing a sequential olefination strategy. Subsequent macrolactonization and a final two-step oxidation sequence were the principle steps used to complete the synthesis. Six of the seven syn-stereochemical relationships (C6−C7, C10−C11, and C14−C15) were introduced using our asymmetric crotylation bond construction methodology. The C12 stereocenter was introduced by an alkoxy-directed hydroboration reaction. An alternative strategy for introducing the C10 stereo center via a diastereoselective hydroboration reaction of 1,1-disubstituted olefin 6b provided a more atom efficient approach to intermediate 7 .",10.1021/ja974318b,1998-04-17,0.635058848892289
Synthesis,A Practical Formal Synthesis of <scp>d</scp>-(+)-Biotin from 4-Formylazetidin-2-one,"A practical synthesis of (3S,6R)-1,3-dibenzyltetrahydro-1H-furo[3,4-d]imidazole-2,4-dione, an important intermediate in the synthesis of biotin, from 4-formyl-3-mesyloxyazetidin-2-one has been achieved. Acid-catalyzed azetidin-2-one ring opening followed by a one-pot conversion of diamine hydrochloride to a cyclic urea and hydroxymethylene to chloromethylene by triphosgene to obtain (4S,5R)-methyl-1,3-dibenzyl-5-chloromethyl-2-oxoimidazolidine-4-carboxylate is the key step in this synthesis.",10.1055/s-2007-965992,2007-04-01,0.6350569347801075
Organic Letters,Enantioselective Total Synthesis of Aspergillide C,"The first enantioselective total synthesis of aspergillide C, a cytotoxic 14-membered macrolide isolated from the marine-derived fungus Aspergillus ostianus, has been accomplished from a commercially available chiral glycidol derivative by a 12-step sequence involving an expeditious preparation of a cyclic acetal intermediate and a trans-selective Ferrier-type two-carbon homologation reaction.",10.1021/ol802803x,2009-01-07,0.6350260436609448
Synlett,Formal Synthesis of Hepatitis C Virus NS5B Polymerase Inhibitor,A formal synthesis of a hepatitis C virus (HCV) inhibitor is described. The synthesis features a benzyne-mediated one-pot indoline formation–methylation sequence and an In(OTf) 3 -mediated mild oxa-Pictet–Spengler reaction for the synthesis of substituted electron-rich pyranoindole.,10.1055/s-0033-1339522,2013-08-26,0.6350107866030661
Tetrahedron,"A novel route to thioketenes by flash vacuum thermolysis of silylatedketene dithioacetals, synthesis of propadienethione.",,10.1016/s0040-4039(00)94262-x,1986-01-01,0.6350094723215609
European Journal of Organic Chemistry,Protecting‐Group‐Free Total Synthesis of (−)‐Boscartin A in 3 Steps from (−)‐Boscartin F via Wharton Reaction,"Abstract In this report, we described the first total synthesis of (−)‐boscartin A, a cembranoid featuring a 5/5/12‐fused tricyclic structure. Via the key reactions, including stereoselective epoxidation and Wharton reaction, (−)‐Boscartin A was obtained in three steps from (−)‐boscartin F, with 46 % overall yield.",10.1002/ejoc.202201366,2022-11-26,0.635004293142362
Organic Letters,Synthesis of the Reported Structure of Pogostol and a Total Synthesis of (±)-Kessane without the Use of Protecting Groups,[reaction: see text] A short racemic synthesis of kessane from 4-hydroxy-4-methyl-2-cyclohexenone is described using a route that also resulted in the synthesis of the reported structure of pogostol. The key step involves an Fe(III)-mediated tandem radical ring-expansion/cyclization of the cyclopropylsilyl ether 9. No protecting groups are used in the entire sequence. Comparison of the NMR data of synthetic pogostol to that in the literature indicates that the structure originally proposed is incorrect.,10.1021/ol035373u,2003-08-08,0.6349878140547128
Organic Letters,Stereoselective Total Synthesis of Bistramide A,A highly stereoselective and convergent total synthesis of bistramide A is described. The salient feature of this synthesis is the construction of the spiroketal subunit by hydrolysis of dialkylated tosylmethyl isocyanide derivative derived via alkylation of TosMIC with suitably substituted halohydrin derivatives.,10.1021/ol702095n,2007-10-01,0.6349728965792165
Tetrahedron,Development of a scalable synthesis of a nonbasic inhibitor of the serine protease tryptase,,10.1016/j.tetlet.2006.04.149,2006-05-23,0.6349714855379452
Green Chemistry,Intermediate oxiranes in the base-catalyzed depolymerisation of lignin,"Quantum calculations show that βO4′ links break in two ways; the carbanion route yields monomers, the alkoxide route facilitates repolymerisation.",10.1039/c5gc02192h,2015-10-27,0.6349647238319673
Synthesis,A Convergent Route to 5-(Arylsulfanyl)-6-sulfonamido-3-benzofuranones,"All articles of this category A procedure for the synthesis of 5-(arylsulfanyl)-2,3-dihydro-6-sulfonamido-3-benzofuranones ( 1 ) via 5-bromo-3-methoxy-6-nitrobenzofuran ( 4 ) as a common advanced synthetic intermediate has been developed. The key step consists of a regioselective nucleophilic aromatic substitution of the bromine atom of 4 by an aryl or heteroarylthiol. nucleophilic aromatic substitutions - heterocycles - benzofuranones - sulfonamides - drugs",10.1055/s-2000-6396,2000-01-01,0.6349527593153341
Synlett,"A Novel Synthesis of the 2-Aminoimidazol-4-carbaldehyde Derivatives, Versatile Synthetic Intermediates for 2-Aminoimidazole Alkaloids","The title synthesis was achieved by the reaction of t-but­oxycarbonylguanidine with 3-bromo-1,1-dimethoxypropan-2-one as a key step. Starting with 1-tert-butoxycarbonyl-2-tert-butoxycarbonylaminoimidazol-4-carbaldehyde thus obtained expeditious synthesis of oroidin, hymenidin, dispacamide and monobromodispacamide, the representative 2-aminoimidazole alkaloids, was accomplished.",10.1055/s-2006-950250,2006-10-01,0.6349417446900376
Tetrahedron,A norbornyl route to aminocyclohexitols: syntheses of diverse aminocarbasugars and ‘confused’ aminocarbasugars,,10.1016/s0040-4039(01)02125-6,2002-01-01,0.6349351376103822
European Journal of Organic Chemistry,Formal Total Synthesis of (–)‐Raphidecursinol B,"Abstract An efficient enantioselective formal total synthesis of antimalarial natural product (–)‐raphidecursinol B along with its all stereoisomers is described from commercially available 3,4,5‐trimethoxybenzaldehyde using the Sharpless asymmetric dihydroxylation, regioselective α‐tosylation, epoxide opening and Mitsunobu reaction as the key reaction steps.",10.1002/ejoc.201000619,2010-07-28,0.6349188219310543
Organic Letters,Formal Synthesis of Dictyodendrin B,"A formal synthesis of dictyodendrin B is described. Regiocontrolled functionalization of the α,β-dibromopyrrole derivative provided the fully substituted pyrrole bearing an indole moiety. Subsequent reductive cyclization using a combination of sodium dispersion and triethylsilyl chloride enabled the formation of the benzene ring in the characteristic tetracyclic pyrrolo[2,3- c ]carbazole skeleton, while the ethyl ester remained untouched. Further chemical transformation of the ester moiety and functional group manipulation completed the formal synthesis of dictyodendrin B.",10.1021/acs.orglett.3c00746,2023-04-06,0.6349172585358411
Synthesis,Chemoenzymatic Synthesis of arabino-Configured Bicyclic Nucleosides,"Abstract A convergent route for the synthesis of a new class of bicyclic nucleosides has been developed. The synthetic route to the corresponding arabino-configured uracil and thymine bicyclic nucleosides proceeds in 24 and 27% overall yields, respectively, starting from 1,2,5,6-di-O-isopropylidene-α-d-glucofuranose. This synthetic protocol includes some crucial steps such as Vorbrüggen base coupling and chemo-enzymatic regioselective acetylation of the primary hydroxyl group by using Lipozyme® TL IM where it was found that Lipozyme® TL IM could be recovered and reused for selective acetylation without losing its selectivity.",10.1055/s-0041-1738440,2023-05-22,0.634916318159436
Journal of the American Chemical Society,[3 + 2] Annulation of Allylic Silanes in Acyclic Stereocontrol:  Total Synthesis of (9<i>S</i>)-Dihydroerythronolide A,"The [3 + 2] annulation reactions of allylic silanes can be utilized to achieve acyclic stereocontrol. This method was employed as a key step in an enantioselective total synthesis of (9S)-dihydroerythronolide A. The key annulation reaction served to establish most of the stereochemistry of the target, including the two tetrasubstituted carbon stereocenters. The symmetry of the target molecule allowed it to be disconnected into two equally sized fragments, both of which were generated from the same annulation reaction. The two fragments were coupled using a tin(II)-mediated chelation-controlled aldol reaction of an alpha-benzyloxy ethyl ketone. This convergent total synthesis of (9S)-dihydroerythronolide A was accomplished with the longest linear sequence of 29 steps and in 5.4% overall yield.",10.1021/ja034865z,2003-04-25,0.6348996079390428
Angewandte Chemie International Edition,Total Synthesis of Paliurine F,"A couple of coppers: An efficient, asymmetric synthesis of the sedative cyclopeptide alkaloid paliurine F has been achieved. The strategy employs two copper(I)-mediated coupling reactions as key steps to install the aryl ether linkage as well as to form the enamide with a concomitant unprecedented macrocyclization.",10.1002/anie.200602865,2006-10-11,0.6348807691275374
European Journal of Organic Chemistry,"First Total Synthesis of Deinococcucin A, a Key Glycolipid Found in Cell Membranes of Extremophilic Bacteria","Abstract Deinococcucin A is a secondary metabolite isolated from a gut bacteria of carpenter ant, member of extremophilic Deinoccocus family. The structure is a glycolipid containing N ‐acetyl glucosamine, linked in α anomeric position to a chiral 2,3‐dihydroxypropanamide moiety. We succeeded a new strategy starting directly from N ‐acetylglucosamine and transforming in an efficient manner an allyl group to the corresponding chiral α‐hydroxyamide. Three key steps were used: the oxidation of primary amine to nitrile using TCCA, as well as its hydrolysis to the corresponding amide using palladium (II) catalyzed conditions. The synthesis was completed in only 10 steps with an overall yield of 3 %.",10.1002/ejoc.202400879,2024-11-06,0.6348763597007058
Synthesis,Total Synthesis of Lagerstannin C: Follow-up of the Khanbabaee’s Synthesis,"This report describes the total synthesis of lagerstannin C, a natural ellagitannin that has d-gluconic acid in the molecule. The study presented here is the first synthesis of the gluconic acid containing ellagitannin. The key step in the synthesis is the opening of δ-lactone through transesterification to form the corresponding benzyl ester.",10.1055/s-0036-1588477,2017-07-20,0.634868000889566
Journal of Organic Chemistry,Assembly of a Key Dienic Intermediate for Tetrodotoxin via a Machetti–DeSarlo Reaction,"A route to a racemic diene intermediate for the synthesis of tetrodotoxin is described. Key steps of the sequence leading to such a compound include the oxidative amidation of a phenol, a Cu(II)-catalyzed cyclocondensation of a nitroketone with an olefin (Machetti-DeSarlo reaction), and a nucleophilic fragmentation of the resulting isoxazoline. Several unusual reactions encountered in the course of this study are thoroughly discussed.",10.1021/jo401960p,2013-10-27,0.6348679369510665
Journal of Organic Chemistry,Straightforward Synthesis of Panaxytriol:  An Active Component of Red Ginseng,"A total synthesis of (3R,9R,10R)-panaxytriol (1) was accomplished enantioselectively (40% overall yield; 30% for the longest sequence). A key step was a Cadiot-Chodkiewicz cross-coupling reaction on two fragments containing, in the aggregate, three unprotected hydroxyl groups. One fragment was synthesized by a highly enantioselective reduction of an enynone. The other arose from a highly enantioselective dihydroxylation of an allylic alcohol.",10.1021/jo0341665,2003-04-29,0.6348643566661359
Journal of Organic Chemistry,Total Synthesis of (−)-Fasicularin,"Asymmetric total synthesis of (-)-fasicularin was achieved in nine steps from a commercially available inexpensive material, by leveraging (1) an aryl radical-mediated, copper-catalyzed Sonogashira-type cross-coupling, (2) a Au-catalyzed tandem intramolecular alkyne hydroamination/iminium formation/intramolecular allylation, and (3) a tandem hydrogenation/hydrogenolysis/intramolecular reductive amination as key transformations.",10.1021/acs.joc.4c01447,2024-07-31,0.634857958167133
Tetrahedron,Reduction of triethyllead cation - a novel route to generate ethyl radicals,,10.1016/0040-4039(64)83026-4,1964-01-01,0.6348408477615777
Journal of the American Chemical Society,Enantioselective Double Michael Addition/Cyclization with an Oxygen-Centered Nucleophile as the First Step in a Concise Synthesis of Natural (+)-Asteriscanolide,"The total synthesis of (+)-asteriscanolide ( 1 ) starting from 2-bromo-4,4-dimethylcyclopentenone has been accomplished. The synthetic route features two key steps. The first step is an unprecedented Michael−Michael reaction sequence that involves a heteronucleophile and proceeds with complete asymmetric induction. The two five-membered rings of the target molecule are thereby generated enantioselectively in a single laboratory step. The second step is based on utilization of ring-closing metathesis to provide an eight-membered ring in which a conjugated 1,3-diene unit resides. Other features of the synthetic stratagem involve the utilization of singlet oxygen in a regiocontrolled ene reaction, the fully stereocontrolled hydrogenation of a dienone, and a chemoselective ruthenium tetraoxide oxidation.",10.1021/ja994053w,2000-03-01,0.6348293967698945
Organic Letters,"Synthesis of <i>syn</i>-1,3-Aminoalcohols via a Ru-Catalyzed <i>N</i>-Demethylative Rearrangement of Isoxazolidines and Its Application in a Three-Step Total Synthesis of HPA-12","A highly efficient ruthenium-catalyzed stereospecific N-demethylative rearrangement of isoxazolidines to synthetically useful N-H-1,3-oxazinanes is described. 1,3-Oxazinanes are useful building blocks, which can be further converted to N-H-1,3-aminoalcohols in one step. This new method was used in a three-step gram-scale total synthesis of HPA-12 in an overall 24% yield.",10.1021/ol502956j,2014-10-27,0.6348236170083713
Synlett,"An Efficient Synthesis of 2,3-Aziridino-γ-lactones from Azetidin-2-ones","An efficient synthesis of enantiopure 2,3-aziridino-γ-lactones from azetidin-2-ones is described. Acid-catalyzed tandem intramolecular azetidinone ring opening followed by aziridine ring formation via elimination of a mesylate group is the key step in this synthesis. 2,3-Aziridino-γ-lactones are important precursors for ­biologically important glutamic acid derivatives.",10.1055/s-2005-872263,2005-01-01,0.6348056155843057
Journal of the American Chemical Society,Enantioselective Total Synthesis of (−)-Himalensine A via a Palladium and 4-Hydroxyproline Co-catalyzed Desymmetrization of Vinyl-bromide-tethered Cyclohexanones,"High Resolution Image Download MS PowerPoint Slide Herein, we describe the convergent enantioselective total synthesis of himalensine A in 18 steps, enabled by a highly enantio- and diastereoselective construction of the morphan core via a palladium/hydroxy proline co-catalyzed desymmetrization of vinyl-bromide-tethered cyclohexanones. The reaction pathway was illuminated by density functional theory calculations, which support an intramolecular Heck reaction of an in situ -generated enamine intermediate, where exquisite enantioselectivity arises from intramolecular carboxylate coordination to the vinyl palladium species in the rate- and enantio-determining carbopalladation steps. The reaction tolerates diverse N -derivatives, all-carbon quaternary centers, and trisubstituted olefins, providing access to molecular scaffolds found in a range of complex natural products. Following large-scale preparation of a key substrate and installation of a β-substituted enone moiety, the rapid construction of himalensine A was achieved using a highly convergent strategy based on an amide coupling/Michael addition/allylation/ring-closing metathesis sequence which allowed the introduction of three of the five rings in only three synthetic steps (after telescoping). Moreover, our strategy provides a new enantioselective access to a known tetracyclic late-stage intermediate that has been used previously in the synthesis of many Daphniphyllum alkaloids.",10.1021/jacs.2c13710,2023-02-23,0.6347900157722918
Journal of Organic Chemistry,Alternative Synthesis of the Colorado Potato Beetle Pheromone,"A concise preparation of the pheromone secreted by the male Colorado potato beetle [viz. (3S)-1,3-dihydroxy-3,7-dimethyl-6-octen-2-one] was accomplished in four steps starting from 2-fluoronerol or 2-fluorogeraniol. The key step in the synthesis involves a 6-endo epoxide ring-opening with ester participation that simultaneously inverts the 3R-configuration of the (3R)-2,3-epoxy-2-fluoroprenyl acetate intermediate and installs the ketone functionality of the semiochemical. Extensive NMR studies validate the proposed 6-endo mechanism of the featured rearrangement, which under anhydrous conditions resulted in the formation of two bicyclic 1,3-dioxan-5-ones via an unprecedented intramolecular Prins cyclization.",10.1021/jo4017056,2013-09-18,0.6347873558154377
Journal of Organic Chemistry,"Acid-Catalyzed Cyclization of 2,3-Dibenzylidenesuccinates:  Synthesis of Lignans (±)-Cagayanin and (±)-Galbulin","Acid-catalyzed cyclizations of E,E-dibenzylidenesuccinate esters have been developed as an efficient synthetic route to 1-aryl-1,2-dihydronaphthalenes. This reaction has been used in the synthesis of the naturally occurring lignans (+/-)-cagayanin and (+/-)-galbulin.",10.1021/jo0161025,2001-11-14,0.6347845298828847
Angewandte Chemie International Edition,Total Synthesis of (−)-Spirotryprostatin B and Three Stereoisomers,Heck cyclization and trapping of the resultant η3-allylpalladium intermediate by a tethered diketopiperazine is the central step in a new stereocontrolled route to spirotryprostatin alkaloids. The versatility of this approach is illustrated by the enantioselective total syntheses of the fungal natural product (−)-spirotryprostatin B (1) and three stereoisomers.,10.1002/1521-3773(20001215)39:24<4596::aid-anie4596>3.0.co;2-f,2000-12-15,0.6347611054848395
Angewandte Chemie International Edition,Total Synthesis of (−)-Spirotryprostatin B and Three Stereoisomers,Heck cyclization and trapping of the resultant η3-allylpalladium intermediate by a tethered diketopiperazine is the central step in a new stereocontrolled route to spirotryprostatin alkaloids. The versatility of this approach is illustrated by the enantioselective total syntheses of the fungal natural product (−)-spirotryprostatin B (1) and three stereoisomers.,10.1002/1521-3773(20001215)39:24<4596::aid-anie4596>3.3.co;2-6,2000-12-15,0.6347611054848395
Angewandte Chemie International Edition,"Divergent Biomimetic Total Syntheses of Ganocins A–C, Ganocochlearins C and D, and Cochlearol T","A divergent synthetic approach to six Ganoderma meroterpenoids, namely ganocins A-C, ganocochlearins C and D, and cochlearol T, has been developed for the first time. This synthetic route features a two-phase strategy which includes early-stage rapid construction of a common planar tricyclic intermediate followed by highly selective late-stage transformations into various Ganoderma meroterpenoids. Key to the strategy are a bioinspired intramolecular hetero-Diels-Alder reaction and Stahl-type oxidative aromatization, allowing efficient formation of the common tricyclic phenol intermediate. A nucleophilic dearomatization of the phenol unit, combined with a regioselective 1,4-reduction of the resulting dienone, enabled rapid access to ganocins B and C. Additionally, site-selective Mukaiyama hydration, followed by an intramolecular oxa-Michael addition/triflation cascade, served as a key strategic element in the chemical synthesis of ganocin A.",10.1002/anie.202000677,2020-02-25,0.6347582090616631
Organic Letters,Bidirectional Synthesis of the Central Amino Acid of Chloptosin,"[reaction: see text] An efficient total synthesis of (2S,2'S,3aR,3'aR,8aR,8'aR)-6,6'-dichloro-3a,3'a-dihydroxy-1,1',2,2',3,3a,3',3'a,8,8a,8',8'a-dodecahydro-5,5'-bipyrrolo[2,3-b]indole-2,2'-dicarboxylic acid, the central amino acid component of chloptosin (1), is described. Starting from m-chloronitrobenzene, this C(2)-symmetrical amino acid was synthesized by using a 14-step route, in which a Zinin benzidine rearrangement, intramolecular Heck reaction, and selenocyclization and oxidative deselenation served as key steps. The absolute stereochemistry of the target was confirmed by X-ray single-crystal studies on a key intermediate (17).",10.1021/ol0620139,2006-09-14,0.6347543923503767
Synlett,Enantioselective Synthesis of γ-Hydroxynorvaline,All articles of this category A new synthesis of enantiomerically pure γ-hydroxynorvaline is described. The key step involves diastereoselective alkylation of the chiral Schiff base 1 with primary iodo derivatives 2 easily prepared from propylene oxide. γ-hydroxynorvaline - alkylation - 2-hydroxypinan-3-one - epoxide,10.1055/s-1997-3246,1997-06-01,0.6347489555583214
Organic Process Research & Development,A Facile Total Synthesis of Imatinib Base and Its Analogues,Imatinib and its analogues were successfully synthesized by an improved method in 19.5– 46.2% total yield of six main steps. Pyrimidinyl amine was prepared by the reaction of enaminone and guanidine nitrate without the use of a toxic cyanamide. N -(2-Methyl-5-nitrophenyl)-4-(pyridin-3-yl) pyrimidin-2-amine as a key intermediate for the synthesis of imatinib was prepared by copper-catalyzed N -arylation of heteroarylamine in 82% yield. The copper salts were used instead of the expensive palladium compounds in this C−N bond-forming reaction. The intermediate nitro compound was reduced by a N 2 H 4 ·H 2 O/FeCl 3 /C system using water as a solvent in good yield.,10.1021/op700270n,2008-04-15,0.6347314606719101
Organic Letters,Synthesis of a Complex and Highly Potent PCSK9 Inhibitor,"The solution-based gram-scale synthesis of complex and highly potent proprotein convertase subtilisin-like/kexin type 9 (PCSK9) inhibitor 1 is presented. Construction of Northern fragment 2, followed by stepwise installation of Eastern 3, Southern 4, and Western 5 fragments, provided macrocyclic precursor 19 . This intermediate was cross-linked via an intramolecular azide–alkyne click reaction, which preceded macrolactamization to afford the core framework of compound 1 . Finally, coupling with poly(ethylene glycol) side-chain-based 6 gave the PCSK9 inhibitor 1 .",10.1021/acs.orglett.3c01635,2023-06-29,0.6346837795168117
Journal of Organic Chemistry,Total Synthesis and Biological Evaluation of Pacidamycin D and Its 3′-Hydroxy Analogue,"Full details of the total synthesis of pacidamycin D (4) and its 3'-hydroxy analogue 32 are described. The chemically labile Z-oxyacyl enamide moiety is the most challenging chemical structure found in uridylpeptide natural products. Key elements of our approach to the synthesis of 4 include the efficient and stereocontrolled construction of the Z-oxyvinyl halides 6 and 7 and their copper-catalyzed cross-coupling with the tetrapeptide carboxamide 5, a thermally unstable compound containing a number of potentially reactive functional groups. This synthetic route also allowed us to easily prepare 3'-hydroxy analogue 32. The assemblage by cross-coupling of the Z-oxyvinyl halide 6 and the carboxamide 5 at a late stage of the synthesis provided ready access to a range of uridylpeptide antibiotics and their analogues, despite their inherent labile nature with potential epimerization, simply by altering the tetrapeptide moiety.",10.1021/jo202159q,2011-12-22,0.6346820553225048
Organic Letters,A Claisen Approach to 4′-Ed4T,"An efficient, stereoselective synthesis of 4'-Ed4T is demonstrated. The synthesis is highlighted by a regioselective TMSOTf-mediated acetal opening, a Claisen rearrangement to set the key 4'-stereocenter as well as the olefin, and a one-pot nonaflation/elimination to deliver the alkyne moiety. The synthesis proceeds in eight steps from 5-methyluridine and occurs in 37% overall yield.",10.1021/ol503095v,2014-12-18,0.6346805728812481
Journal of Organic Chemistry,Stereoselective Route to the Ezoaminuroic Acid Core of the Ezomycins,"Starting from readily available (R)-glycidol, an efficient pathway to a strategically functionalized ezoaminuroic acid derivative of the antifungal ezomycins has been developed. A key transformation in the synthesis involves regio- and stereoselective conversion of the olefinic functionality of a 5,6-dihydropyran-2-one to the C-2, C-3 trans-1,2-amino alcohol moiety as present in ezoaminuroic acid.",10.1021/jo051086n,2005-07-14,0.6346735908503885
Organic Process Research & Development,Development of a Kilogram-Scale Synthesis of a Novel MC1R Agonist,"Herein, we report the kilogram-scale synthesis of CD08108, a novel MC1R agonist. This synthesis has been developed to produce the first batches of this compound for preclinical and clinical studies. Two amido couplings were used to synthesize the backbone of the API. Improvements have been made to isolate crystalline intermediates and to remove all column chromatographic steps. Crystallization of the final API was monitored by DSC in-process control during slurry ripening of the amorphous suspension of the hydrochloride salt.",10.1021/acs.oprd.5b00097,2015-05-29,0.6346725733917992
Organic Process Research & Development,Synthesis of a Sodium–Hydrogen Exchange Type 1 Inhibitor: An Efficient Cu-Catalyzed Conjugated Addition of a Grignard Reagent to an Acetyl Pyridinium Salt,"A facile and economical five-step process for the synthesis of a sodium–hydrogen exchange type I inhibitor (NHE-1) was developed from readily available starting materials in 43% overall yield. Key transformations included a highly efficient copper-catalyzed conjugate addition of 2-trifluoromethylphenyl Grignard reagents to acetyl pyridinium salts, a facile hydrogenation of 4-aryl dihydropyridines, a regioselective aromatic bromination, an efficient palladium-catalyzed carbonylation of aryl bromides, and a high-yielding acyl guanidine formation. A safe and scalable protocol for preparation of 2-trifluoromethyl phenyl Grignard reagent was developed, and a facile method for controlling the palladium content with N -acetyl- L -cysteine as the scavenger was demonstrated. Process issues in controlling the formation of a key diacylation side product during acyl guanidine formation are also addressed.",10.1021/op300331b,2013-01-18,0.6346700801691015
Angewandte Chemie International Edition,Novel One-Step Synthesis of Oxocyclopentanecarboxylates through Electroreduction of Cinnamate Derivatives,,10.1002/anie.198300700,1983-01-01,0.6346677420691913
Tetrahedron,"A novel one-step synthesis of dibenzo-1,4-diazepines from acridine derivatives",,10.1016/s0040-4039(01)97510-0,1971-01-01,0.6346677420691913
European Journal of Organic Chemistry,A Fully Palladium‐Mediated Construction of Phenanthrenes and Naphthoxindoles,"Abstract A fully palladium‐catalyzed synthesis of unusual naphthoxindole alkaloids through a key intramolecular direct C–H arylation step leading to the formation of the phenanthrene core is described. The three‐step process involves a highly efficient Heck coupling of aryl diazonium salts with phenylacrylates, giving the corresponding cis ‐stilbenes. Cyclization of stilbenes into phenanthrenes through a direct intramolecular C–H arylation, followed by a palladium‐mediated cyclization of an amino ester, led to the formation of novel naphthoxindoles.",10.1002/ejoc.201100477,2011-06-21,0.6346488754428535
Journal of Organic Chemistry,Stereoselective Synthesis of (−)-Cephalotaxine and C-7 Alkylated Analogues,"A total asymmetric synthesis of (-)-cephalotaxine is reported. The chemistry of alpha,beta-unsaturated gamma-lactams was used to access the 1-azaspiro[4.4]nonane skeleton in enantiomerically pure form via a stereocontrolled semipinacolic rearrangement of an alpha-hydroxyiminium ion. This spiro compound was transformed into (-)-cephalotaxine without any racemization or epimerization by following the racemic synthesis reported by Kuehne. We thus performed a total synthesis of (-)-cephalotaxine in 98.7% ee with an overall yield of 9.8% over a 16 steps sequence. This synthetic process was adaptable to the access of some alkylated analogues.",10.1021/jo049884l,2004-04-01,0.634642381549348
Organic Process Research & Development,Convergent Approach for Commercial Synthesis of Gefitinib and Erlotinib,"An efficient, economical and large-scale convergent synthesis of epidermal growth factor receptor- tyrosine kinase inhibitors gefitinib (1, Iressa) and erlotinib (2, Tarceva) approved by U.S. FDA for the treatment of non-small-cell lung cancer is described. The formation of 4-anilinoquinazolines are achieved in a simple one-pot reaction of suitable formamidine intermediates and substituted anilines involving Dimroth rearrangement, thereby avoiding the need to make quinazolin-4(3 H )-one intermediates, which require a large experimental inputs. Using this process, we have produced drug candidates 1 with overall yield of 66% from 4-methoxy-5-[3-(4-morpholinyl) propoxy]-2-nitrobenzonitrile (3) and 2 with 63% from 4,5-bis(2-methoxyethoxy)-2-nitrobenzonitrile (6) on a multigram scale.",10.1021/op700054p,2007-07-24,0.6346244340917204
Angewandte Chemie International Edition,Total Synthesis of (±)‐Baphicacanthcusine A Enabled by Sequential Ring Contractions,"Reported herein is the first total synthesis of the poly-pseudoindoxyl natural product baphicacanthcusine A. The synthesis leverages the oxidative rearrangement of indoles to pseudoindoxyls to install vicinal pseudoindoxyl heterocycles in a diastereoselective manner. Key steps include an acid-mediated cyclization/indole transposition, two diastereoselective oxidative ring contractions, and a site-selective C-H oxygenation. The synthesis of the oxidation precursors was guided by recognition of an element of hidden symmetry. This work provides a foundation for the chemical synthesis of other poly-pseudoindoxyl alkaloids.",10.1002/anie.202409139,2024-07-12,0.6346078030060744
Organic Letters,Enantioselective Total Synthesis and Assignment of the Absolute Configuration of the Meroterpenoid (+)-Taondiol,"The first enantioselective total synthesis of (+)-taondiol, a pentacyclic marine meroterpenoid, has been achieved, which in addition to confirming the structure also established the absolute configuration of the natural product. The notable points in the synthetic route are synthesis of a highly functionalized tricyclic diterpenoid moiety starting from an enantiopure Wieland-Miescher ketone derivative in concise manner via Robinson-type annulation and an elegant hydrogen atom transfer olefin reduction followed by Lewis acid-catalyzed Friedel-Crafts reaction for one-pot C-C and C-O bond formations resulting in construction of the pentacyclic meroterpenoid skeleton.",10.1021/acs.orglett.8b00997,2018-04-19,0.6346044109945768
Tetrahedron,A new family of five-carbon iminoalditols which are potent glycosidase inhibitors,"The synthesis of 1,5-dideoxy-1,5-imino-D-xylitol 2 (and the enantiomeric iminoalditols 3 and 4) is described. Alditol 2 compares favorably with 1-deoxynojirimycin 1 as a potent inhibitor of β-glucosidase.",10.1016/s0040-4039(00)97405-7,1990-01-01,0.6345918409142526
Chemical Science,Asymmetric synthesis of (−)-naltrexone,", a method that has not previously been reported either for the synthesis or semi-synthesis of opioids. The longest linear sequence is 17 steps, and because the stereogenic centers in the product rely on Sharpless asymmetric dihydroxylation, the route could be used to access either enantiomer of the natural product, which have disparate biological activities. The route also may be applicable to the preparation of opioid derivatives that could not be easily prepared from the more fully elaborated and densely functionalized opioid natural products that have traditionally served as the starting inputs.",10.1039/c8sc03748e,2018-10-23,0.6345764309693724
Organic Letters,Total Synthesis of (±)-Biphyscion,"[formula: see text] A regiospecific total synthesis of (+/-)-biphyscion (1) is described. A novel aspect of the plan was construction of the bianthraquinone ring system from a biphenyl intermediate through the use of a one-pot, double isobenzofuranone condensation.",10.1021/ol990758r,1999-07-08,0.634553145144095
Synlett,"Total Synthesis of ArylomycinA<sub>2</sub>, a Signal Peptidase I (SPase I) Inhibitor","A concise total synthesis of arylomycin A2 was accomplished featuring a key intramol. Suzuki-Miyaura reaction for the formation of the 14-membered meta,meta-cyclophane and direct coupling of a fully elaborated peptide side-chain with the macrocyclic core. [on SciFinder (R)]",10.1055/s-2008-1078209,2008-08-22,0.6345503224708406
Organic Letters,Gram Scale Synthesis of the C(18)−C(34) Fragment of Amphidinolide C,"The synthesis of the C(18)-C(34) fragment of amphidinolide C has been achieved via two routes, culminating in both the shortest (11 steps) and highest yielding (26% overall yield) approaches to this segment. The highly convergent approach will facilitate the synthesis of analogues, including the C(18)-C(29) fragment of amphidinolide F. Synthetic highlights include the selective methylation of a diyne, and the highly efficient use of a second generation cobalt catalyst in the Mukaiyama oxidative cyclization to form the trans-THF ring.",10.1021/ol1030074,2011-01-21,0.6345500780193428
Synlett,"Efficient Stereodivergent Synthesis of <i>cis</i>-(2<i>R</i>,4<i>S</i>)-<i> </i>and <i>trans</i>-(2<i>R</i>,4<i>R</i>)-4-Phosphonomethyl-2-piperidinecarboxylic Acids from the Same Chiral Imine Derived from (<i>R</i>)-Glyceraldehyde","Two diastereomeric 4-phosphonomethyl-2-piperidinecarboxylic acids have been prepared in ca. 20% overall yield starting from the easily accessible N-[(S)-1-phenylethyl]-(S)-2,3-di-O-benzylglyceraldimine. The key step for the stereodivergent synthesis is the asymmetric reduction of an exocyclic C=C double bond on a highly functionalized chiral intermediate. This intermediate is ­obtained by Horner-Wadsworth-Emmons (HWE) reaction of a ­piperidone derived from the cycloadduct obtained in the aza ­Diels-Alder reaction between N-[(S)-1-phenylethyl]-(S)-2,3-di-O-benzylglyceraldimine and Danishefsky’s diene. In these synthetic routes two new stereogenic centres are created on the piperidine ring with very good or excellent stereoselectivity.",10.1055/s-2006-950272,2006-10-01,0.6345478069227736
Tetrahedron,Convergent synthesis of a 24-membered macrocyclic hexaoxazole derivative related to the novel telomerase inhibitor telomestatin,,10.1016/j.tetlet.2006.09.014,2006-09-27,0.6345309117413709
Synthesis,Synthesis of a Dual-Action Cephalosporin: A Novel Approach to 3-Acyloxymethyl-3- cephems,"All articles of this category A practical synthesis of the dual-action cephalosporin 5 from 7-aminocephalosporanic acid (7-ACA), S -benzothiazol-2-yl (2-amino-4-thiazolyl)(methoxyimino)thioacetate (MAEM), and fleroxacin [6,8-difluoro-1-(2-fluoroethyl)-1,4-dihydro-7-(4-methyl-1-piperazi-nyl)-4-oxo-3-quinolinecarboxylic acid, 3 ] is described. Tritylated MAEM prepared in situ was coupled with 7-ACA in dichloromethane followed by hydrolysis of the acetate group to afford the 3-hydroxymethyl-3-cephem 2 . The direct acylation of 2 , which has an unprotected 4-carboxy group, with activated esters of 3 gave mixtures of the desired ester A (4) and the lactone B . The ratio of these two products was found to depend on the nature of the leaving group of the activated ester used, with the one prepared from cyclohexyl chloroformate favoring the formation of 4 . Ester 4 was isolated in more than 50% overall yield from 7-ACA. Removal of the trityl group afforded the dual- action cephalosporin 5 .",10.1055/s-1992-26326,1992-01-01,0.6345302971397039
Organic Process Research & Development,Process Development for the Synthesis of Monocyclic β-Lactam Core 17,"Process development and multikilogram synthesis of the monocyclic β-lactam core 17 for a novel pyridone-conjugated monobactam antibiotic is described. Starting with commercially available 2-(2,2-diethoxyethyl)isoindoline-1,3-dione, the five-step synthesis features several telescoped operations and direct isolations to provide significant improvement in throughput and reduced solvent usage over initial scale-up campaigns. A particular highlight in this effort includes the development of an efficient Staudinger ketene–imine [2 + 2] cycloaddition reaction of N -Boc-glycine ketene 12 and imine 9 to form racemic β-lactam 13 in good isolated yield (66%) and purity (97%). Another key feature in the synthesis involves a classical resolution of racemic amine 15 to afford single enantiomer salt 17 in excellent isolated yield (45%) with high enantiomeric excess (98%).",10.1021/acs.oprd.7b00359,2018-01-04,0.6345264957388742
Journal of the American Chemical Society,13-Step Total Synthesis of Atropurpuran,"Herein, we report a concise total synthesis of atropurpuran, a unique and synthetically challenging pentacyclic diterpene that bears a tetracyclo[5.3.3.0 4,9 .0 4,12 ]-tridecane skeleton that is unprecedented among natural terpenes. This 13-step approach features a strategy that include early stage rapid skeleton formation and the late-stage introduction of reactive functional groups, thus allowed a high overall synthetic efficiency with minimal use of PGs. The key transformations of our work include a facile construction of the spiro[5.5]undecane moiety through an ring-closing enyne metathesis reaction and an efficient formation of the tetracyclo[5.3.3.0 4,9 .0 4,12 ]-tridecane scaffold via an regioselective double oxidative dearomatization/intramolecular Diels–Alder reaction cascade. This efficient approach should also inspire further advances in the synthesis of related complex diterpenes and diterpenoid alkaloids.",10.1021/jacs.9b00391,2019-02-13,0.6345137258976972
Tetrahedron,"Regioselective route for arylnaphthalene lactones: convenient synthesis of taiwanin C, justicidin E, and daurinol",,10.1016/j.tetlet.2013.12.014,2013-12-15,0.6344712043991931
Synlett,A Concise Total Synthesis of (+)-Cladospolide D,"A short and convergent total synthesis of (+)-cladospolide D is delineated, which involves olefin cross metathesis and furan oxidation to access the γ-oxo-α,β-unsaturated acid and Yamaguchi lactonization to construct the 12-membered ring as key steps.",10.1055/s-0032-1317520,2012-11-09,0.6344693926858362
European Journal of Organic Chemistry,"Divergent Total Synthesis of Fornicin A, Fornicin D, and Ganodercin D, Meroterpenoids from <i>Ganoderma</i> Mushrooms","Abstract The meroterpenoids fornicin A, fornicin D, and ganodercin D, found in mushrooms of the Ganoderma genus, have been prepared in a concise and divergent synthesis route. The characteristic unsaturated γ‐ketoacid moiety was obtained via an optimized step‐wise aldol condensation between two readily accessible building blocks. THP‐protection of a phenolic hydroxyl group under basic conditions was developed, a protocol that adds to the versatility of this protecting group.",10.1002/ejoc.202201446,2022-12-27,0.6344672291686115
Tetrahedron,Total synthesis of halichondrins: Enantioselective construction of a homochiral tetracyclic KLMN-ring intermediate from D-mannitol,,10.1016/s0040-4039(00)73673-2,1993-05-01,0.6344514623614284
Tetrahedron,One-step enantioselective synthesis of (4S)-isosclerone through biotranformation of juglone by an endophytic fungus,,10.1016/j.tetlet.2012.12.038,2012-12-24,0.6344390925350399
Synlett,"First Enantioselective Synthesis of (-)-(2<i>S</i>,6<i>S</i>)-(6-Ethyltetrahydropyran-2-yl)formic Acid","We describe in this letter the first enantioselective synthesis of (-)-(2S,6S)-(6-ethyltetrahydropyran-2-yl)formic acid (2) in five steps (30% overall yield, 87% ee), from the commercial chiral template (R)-2,3-isopropylideneglyceraldehyde (4). The two stereogenic centers in 2 were controlled by diastereoselective ­Barbier allylation of 4 in aqueous media and an efficient Prins ­cyclization reaction between 5 with propanal.",10.1055/s-2005-863744,2005-01-01,0.634434415662115
Tetrahedron,A novel synthetic use of trialkyl(indol-2-yl)borate for a “one-pot” synthesis of [a]-annelated indoles,,10.1016/s0040-4039(00)61792-6,1992-11-01,0.6344180926121509
Synlett,A Short Synthesis of (±)-Clavizepine,"All articles of this category A new synthesis of (±)-clavizepine is described which is based on the anionic cyclization of the bromo ester 5 to give the xanthene 9-carboxylate 6 , followed by construction of the azepine ring by intramolecular aromatic substitution of the amido acetal 9 .",10.1055/s-1994-22878,1994-01-01,0.6344007053906617
Journal of Organic Chemistry,Synthesis of Isoquinolones by Sequential Suzuki Coupling of 2-Halobenzonitriles with Vinyl Boronate Followed by Cyclization,"A novel, facile, and expeditious two-step synthesis of 3,4-unsubstituted isoquinolin-1(2 H )-ones from a Suzuki cross-coupling between 2-halobenzonitriles and commercially available vinyl boronates followed by platinum-catalyzed nitrile hydrolysis and cyclization is described.",10.1021/acs.joc.1c00472,2021-05-28,0.6343865644963331
Organic Process Research & Development,"Synthetic Pathways to 2,2-Dimethyl-6-oxo-1-cyclohexaneacetic Acid, a Useful Isoprenoid Building Block","Six new synthetic routes to 2,2-dimethyl-6-oxo-1-cyclohexaneacetic acid ( 1 ) from readily available starting materials have been evaluated. The most efficient method (yield 35%) involves alkylation of Hagemann's ester with ethyl bromoacetate followed by hydrolysis of the resultant ethyl 3-(ethoxycarbonyl)-2-methyl-6-oxo-1-cyclohexeneacetate to unsaturated keto acid 2-methyl-6-oxo-1-cyclohexeneacetic acid ( 19 ) and then treatment of 19 with Me 2 CuLi. A method from mesityl oxide is longer and slightly less efficient (30%). These two methods are suitable for a large-scale preparation of 1 .",10.1021/op960049i,1997-05-01,0.6343813812161239
Synthesis,"An Efficient and HighlyStereoselective Synthesis of<i>gala</i>-Quercitolfrom 1,4-Cyclohexadiene","gala-Quercitol was synthesized from 1,4-cyclohexadiene in seven steps and overall yield of 68%. Reaction of 5,6-dibromo-2,2-dimethylhexahydro-1,3-benzodioxole, synthesized from 1,4-cyclohexadiene in three steps, with excess NaOMe gave (3aalpha,5alpha,7aalpha)-5-methoxy-2,2-dimethyl-3a,4,5,7a-tetrahydro-1,3-benzodioxole. cis-Hydroxylation of the benzodioxole followed by acetylation with AcCl gave 5-O-methyl-gala-quercitol tetraacetate from which gala-quercitol was obtained by hydrolysis and demethylation with aq HBr (47%).",10.1055/s-2003-40517,2003-01-01,0.634380989140279
Tetrahedron,"A new synthetic route to 1,25-dihydroxy-vitamin D3","A synthesis of 1,25-dihydroxy-vitamin D3 using a new acetylenic Ring-A precursor is described. Ring-A synthons 4a or 4b can be prepared in homochiral form by a diastereoselective diazoester cyclization.",10.1016/s0040-4039(00)79918-7,1991-05-01,0.6343059150263007
Journal of Organic Chemistry,Studies Directed toward the Synthesis of the Unusual Antileukemic Diterpene Jatrophatrione. 1. A Solution to the Problem of Chirality Merger during Elaboration of the Entire Carbotricyclic Framework,"A practical route for elaboration of the [5.9.5] tricyclic nucleus of jatrophatrione (1) is reported. The two key steps involve an oxyanionic Cope rearrangement and a Grob fragmentation. The building blocks required to reach 44 are the bicyclo[3.3.0]octanone 29 and the cyclopentadienyl bromide 35. The former was obtained in 12 steps from methylcyclopentadiene. The route to the latter began with 4,4-dimethylcyclopentenone. The charge-accelerated [3,3]-sigmatropic isomerization within 44 proceeds via a chairlike transition state to deliver, after enolate methylation, a highly strained product carrying a trans double bond in a medium-sized ring, one consequence of which is rapid transannular ring closure via an ene pathway. Acid hydrolysis of this enol ether and conversion to hydroxy mesylate 51 was followed by exposure to base. This sequence resulted in ring opening to provide the strategic advanced intermediate 52. The synthetic pathway developed here is expected to open a route to 9-epijatrophatrione (8) for the ultimate purpose of examining its anticipated isomerization to 1 under mildly basic conditions.",10.1021/jo9825254,1999-04-01,0.6343030494620937
Tetrahedron,The chemistry of N-substituted benzotriazoles: a novel route to dienamines,,10.1016/s0040-4039(00)79784-x,1991-07-01,0.6342962222807929
Organic Process Research & Development,Development and Optimization of a Scalable Palladium-Catalyzed C–N Coupling and Acid-Catalyzed Protecting Group Removal Telescope Process for the Synthesis of CDK2-Selective Candidate Tegtociclib (PF-07104091),"PF-07104091 is a cyclin-dependent kinase 2 (CDK2)-selective inhibitor under investigation as an oncology treatment with breast cancer as the leading indication. In this report, we detail the process development and optimization of a telescoped palladium-catalyzed C–N coupling and acid-catalyzed protecting group removal. This optimized process was demonstrated on pilot plant scale production of >700 kg of intermediate 6 .",10.1021/acs.oprd.5c00269,2025-10-09,0.6342632559034559
Organic Process Research & Development,Short Gram-Scale Synthesis of Sulfavant A,"Recently, we reported the promising activity of a novel class of sulfoquinovosyl-diacylglycerols named Sulfavants as molecular vaccine adjuvants. Herein, we describe a modified and improved chemical synthesis of the lead product Sulfavant A ( 1 ), with the aim to produce from milligrams to 10 g of the pure compound that is necessary for the preclinical development. Starting from the versatile synthesis based on the trichloroacetimidate methodology, up-scaled preparation of Sulfavant A ( 1 ) was achieved in 11 steps by elimination and modification of those reactions that negatively affected the overall yield by the previous procedure. The novel strategy gave 17% overall yield of the target compound 1 and also paved the way for the gram-scale preparation of a wide range of other charged and neutral glycoglycerolipids.",10.1021/acs.oprd.0c00393,2020-10-16,0.6342582122323545
Tetrahedron,Concise allene synthesis from propargylic alcohols by hydrostannation and deoxystannylation: A new route to chiral allenes,,10.1016/s0040-4039(00)61198-x,1992-08-01,0.6342559270605581
Organic Letters,Total Synthesis of Enantiopure (+)-γ-Lycorane Using Highly Efficient Pd-Catalyzed Asymmetric Allylic Alkylation,"[reaction: see text] A highly efficient short total synthesis of (+)-gamma-lycorane (>99% ee, 41% overall yield) was achieved by using the asymmetric allylic alkylation in the key step catalyzed by palladium complexes with novel chiral biphenol-based monodentate phosphoramidite ligands.",10.1021/ol060181v,2006-03-01,0.6342403286969592
Synthesis,"Selective [2+2+2] Cycloaddition of Nickel-Benzyne and an Asymmetric 1,3-Diyne: An Iterative Route to Substituted [<i>n</i>]Acenes","A new iterative route to substituted acenes is reported that centers on regioselective cycloaddition of a nickel-benzyne and 1-trimethylsilyl-1,3-pentadiyne. The five-step sequence installs two fused aromatic rings and two methyl substituents onto the backbone in 27% overall yield.",10.1055/s-2004-834894,2004-01-01,0.6342287236596342
Journal of the American Chemical Society,"Total Syntheses of (−)-Lycoricidine, (+)-Lycoricidine, and (+)-Narciclasine via 6-<i>exo</i> Cyclizations of Substituted Vinyl Radicals with Oxime Ethers","The development of an approach to the total synthesis of the title alkaloids is described. The approach utilizes as the key strategic element a stereoselective 6- exo radical cyclization of a vinyl radical to an O -benzyloxime radical acceptor group. The vinyl radical was itself generated by regioselective addition of phenylthiyl radical to a disubstituted alkyne. The regiochemical issues of such additions, which result in different outcomes with tri- n -butylstannyl radicals and phenylthiyl radicals, are discussed. The first such synthesis described, that of (−)-lycoricidine, proceeded in 14 steps and 11% overall yield from 10 and served to develop the radical chemistry required. A second-generation synthesis, this time of the natural (+) enantiomer, was developed using insights gleaned from the first study and proved much more efficient, providing the target alkaloid in nine steps and 44% overall yield. This approach was then employed in the more demanding case of (+)-narciclasine. Several problems arising due to the more electron rich aromatic moiety present in this structure are described. The synthesis developed to deal with these aspects afforded (+)-narciclasine in 12 steps and 26% overall yield.",10.1021/ja9826688,1999-05-22,0.6342247111172556
Synthesis,Facile and Efficient Total Synthesis of Taspine,"The facile and efficient total synthesis of taspine was achieved in 10 steps in high yield (16.5% overall) from commercially available isovanillin. Key steps in the synthesis are preparation of a symmetrical homodimer employing a classical Ullmann coupling reaction, and introduction of an allyl substituent by the Claisen rearrangement reaction. Significantly, the facile synthetic scheme proposed in this work has the characteristics of mild reaction conditions, inexpensive reagents, higher yield, and simple operation.",10.1055/s-0029-1217393,2009-06-08,0.6342133629889769
Organic Letters,Synthesis of Pterocellin A,The first total synthesis of pterocellin A (1) was achieved in 10 linear steps from commercially available kojic acid (6) and 2-bromo-3-pyridinol (11) in a convergent sequence. The key constructive steps are a directed lithiation to couple two pyridines and an intramolecular nucleophilic aromatic substitution to form 1. [structure: see text],10.1021/ol061002c,2006-05-19,0.6342062201197831
Angewandte Chemie International Edition,Brønsted Acid Catalyzed Addition of Enamides to <i>ortho</i>‐Quinone Methide Imines—An Efficient and Highly Enantioselective Synthesis of Chiral Tetrahydroacridines,"The direct and highly enantioselective synthesis of tetrahydroacridines was achieved through the phosphoric acid catalyzed addition of enamides to in situ generated ortho-quinone methide imines and subsequent elimination. This novel one-step process constitutes a very efficient, elegant, and selective synthetic approach to valuable N-heterocycles with a 1,4-dihydroquinoline motif. By subsequent highly diastereoselective hydrogenation and N-deprotection the reaction products were easily converted into free hexahydroacridines with a total of three new stereogenic centers.",10.1002/anie.201604201,2016-06-29,0.6342016388669214
Tetrahedron,A stereospecific synthesis of a renin inhibitor (BW-175) which incorporates a sulfonemethylene isostere and a dihydroxyethylene isostere.,,10.1016/0040-4039(90)80019-i,1990-01-01,0.6341994660471703
Tetrahedron,Stereospecific synthesis of an α-mannosidase inhibitor relatedto swainsonine,,10.1016/s0040-4039(00)89240-0,1985-01-01,0.6341994660471703
Organic Letters,Facile Synthetic Route to Highly Luminescent Sila[7]helicene,A facile synthetic route to dimethylsila[7]helicene by using a Lewis acid catalyzed double-cyclization reaction for construction of the twisted two phenanthrene moieties is described. Sila[7]helicene exhibited a high fluorescence quantum yield and a realatively large g value (dissymmetric factor) of circularly polarized luminencence (CPL) for small molecules.,10.1021/ol4005036,2013-04-15,0.6341994194459326
Organic Letters,"Synthesis of 2-<i>C</i>-Methyl-<scp>d</scp>-Erythritol 2,4-Cyclopyrophosphate","[reaction: see text] The synthesis of 2-C-methyl-D-erythritol 2,4-cyclopyrophosphate, a biochemical intermediate in the deoxyxylulose pathway of isoprenoid biosynthesis, was accomplished in four steps. Bisphosphorylation of 2-C-methyl-D-erythritol 1,3-diacetate, followed by carbodiimide cyclization and deprotection, led to the title compound in 42% overall yield.",10.1021/ol025661a,2002-03-15,0.6341951376619794
Synthesis,"Synthesis of 4-Methoxy-<i>N</i>-{2-[3-(Methylamino)heptyl]phenyl}benzamide, an Antiarrhythmic Compound Related to Encainide","All articles of this category A ring-opened side product 3 , formed during the reduction of a pyridinium precursor to the antiarrhythmic drug, encainide (2) , was isolated. The structure of 3 was confirmed by an independent synthesis from o -iodonitrobenzene and 1-hepten-3-ol. The key step was a palladium(II) catalyzed coupling to introduce the 3-oxoheptyl side chain onto the aromatic ring. Synthetic 3 exhibited significant antiarrhythmic activity.",10.1055/s-1994-25615,1994-01-01,0.6341928747929305
European Journal of Organic Chemistry,An Efficient Formal Synthesis of (−)-Balanol by Using Ruthenium-Catalyzed Asymmetric Hydrogenation,An efficient formal synthesis of (−)-balanol is reported. The ten-step sequence leading to a key precursor 4 features a highly stereoselective synthesis of the functionalized hexahydroazepine core through dynamic kinetic resolution of a racemic α-amido β-keto ester using a ruthenium(II)-catalyzed hydrogenation reaction.,10.1002/1099-0690(200012)2000:23<3903::aid-ejoc3903>3.0.co;2-q,2000-12-01,0.634185311944258
Organic Letters,Enantiospecific Total Synthesis of (−)-Japonicol C,"An efficient and convergent first total syntheses of (±)-japonicol B and (−)-japonicol C have been completed. The notable points of the synthetic route are Lewis-acid-catalyzed Friedel–Crafts reaction for one pot C–C and C–O bond formations resulting in construction of the tricyclic meroterpenoid skeleton, one pot Pd(OH) 2 /C-catalyzed isomerization/hydrogenation, and site selective sp 3 C–H oxidation.",10.1021/acs.orglett.1c00560,2021-03-17,0.6341620161041395
Journal of Organic Chemistry,Total Synthesis of the Potent Microtubule-Stabilizing Agent (+)-Discodermolide,"The total synthesis of the potent microtubule-stabilizing, antimitotic agent (+)-discodermolide is described. The convergent synthetic strategy takes advantage of the diastereoselective alkylation of a ketone enolate to establish the key C15-C16 bond. The synthesis is amenable to preparation of gram-scale quantities of (+)-discodermolide and analogues.",10.1021/jo034521r,2003-07-25,0.6341591662156009
Journal of Organic Chemistry,Stereoselective Synthesis of 2′-Fluoro-6′-methylene Carbocyclic Adenosine via Vince Lactam,"2'-Fluoro-6'-methylene carbocyclic adenosine (FMCA) is a potent and selective inhibitor of wild type as well as drug-resistant hepatitis B virus (HBV) mutants. FMCA demonstrated excellent anti-HBV activity against both adefovir-resistant and lamivudine-resistant double (rtL180M/rtM204V) mutants as well as in lamivudine/entecavir triple mutants (L180M+S202G+M204V) in vitro. Its monophosphate prodrug (FMCAP) demonstrated a greater than 12-fold increase of anti-HBV activity in comparison to that of the nucleoside without elevation of cellular toxicity. In the preliminary in vivo study in chimeric mice harboring the lamivudine/entecavir triple mutant, FMCAP effectively reduced HBV viral load, while entecavir was not effective. Therefore, it was of great interest to develop an efficient synthetic procedure to support the preclinical investigation. In this article, a new approach for the synthesis of FMCA from a readily available starting material (Vince lactam) in 16 steps is described. An efficient and practical methodology for stereospecific preparation of a versatile carbocyclic key intermediate, D-2'-fluoro-6'-methylene cyclopentanol 14, has been developed from diazotization, elimination, stereoselective epoxidation, fluorination, and oxidation-reduction sequence of the Vince lactam in 14 steps. The utility of D-2'-fluoro-6'-methylene cyclopentanol 14 is demonstrated in the preparation of FMCA using the Mitsunobu coupling to introduce the adenine base to synthesize the final nucleoside.",10.1021/jo500382v,2014-04-03,0.6341538658757039
Tetrahedron,A two-step practical synthesis of dehydroalanine derivatives,,10.1016/j.tetlet.2011.01.122,2011-02-02,0.6341524207476693
Journal of Organic Chemistry,"New Synthesis of 1,3-Dihydro-1,4-benzodiazepin-2(2<i>H</i>)-ones and 3-Amino-1,3-dihydro-1,4-benzodiazepin-2(2<i>H</i>)-ones:  Pd-Catalyzed Cross-Coupling of Imidoyl Chlorides with Organoboronic Acids","A new approach to the synthesis of 1,4-benzodiazepines and 3-amino-1,4-benzodiazepines, which employs the Pd-catalyzed cross-coupling reaction of an imidoyl chloride with an organometallic reagent as the key step, is described. A five-step synthesis of a key intermediate is described and it is shown that in only four further steps (three couplings and a TFA-mediated BOC-deprotection) a wide variety of N1-, C3-amino-, C5-carbon-, or nitrogen-substituted 1,4-benzodiazepines can be synthesized.",10.1021/jo026860a,2003-03-07,0.6341501486646767
European Journal of Organic Chemistry,First Asymmetric Synthesis of Boehmeriasin A,"Abstract The first asymmetric synthesis of phenanthroquinolizidinealkaloid ( R )‐boehmeriasin A is described. Two alternative synthetic pathways to the key intermediate ( RS , R )‐ 4 were achieved through a combination of highly diastereoselective 1,2‐nucleophilic addition on (–)‐( S )‐1‐amino‐2‐(methoxymethyl)pyrrolidine hydrazones with a ring‐closing metathesis to ensure the construction of the piperidine template. A subsequent acylation/oxidation/aldol condensation/radical cyclization sequence completed the assembly of the title ( R )‐configured natural product.",10.1002/ejoc.200901404,2010-02-16,0.6341228767533348
Organic Letters,Asymmetric Total Synthesis of (−)-Scabronine G via Intramolecular Double Michael Reaction and Prins Cyclization,The enantioselective total synthesis of (-)-scabronine G is described. The key features of the present synthesis include the construction of a 5-6 ring system containing two quaternary carbon centers via a diastereoselective intramolecular double Michael reaction and the formation of a seven-membered ring using a Prins cyclization.,10.1021/ol200873y,2011-05-06,0.6341192863716615
Journal of Organic Chemistry,A Facile Two-Step Synthesis of 2-Arylbenzofurans Based on the Selective Cross McMurry Couplings,"A novel two-step synthesis of 2-arylbenzofurans has been developed. It involves a selective cross McMurry coupling of a salicylaldehyde or substituted salicylaldehyde with an aromatic aldehyde and a sequential oxidative cyclization of the resulting ortho-vinylphenols. Utilizing this synthetic protocol, a variety of 2-arylbenzofurans including cicerfuran have been efficiently synthesized.",10.1021/jo7019652,2007-11-21,0.6341120857096123
Angewandte Chemie International Edition,Core Modification of Cytisine: A Modular Synthesis,"Getting down to the core: A novel, modular, and more robust synthesis of cytisine, a partial agonist selective for the α4β2 nicotinic acetylcholine receptor, also allows modification of the core structure, as exemplified by the first azacytisine and a cytisine–varenicline hybrid. Key steps include Stille coupling of heteroarylstannanes with a bromolactam motif and an in situ epimerization/alkylative cyclization to complete the tricyclic core (see scheme).",10.1002/anie.201100441,2011-04-21,0.6341106977339068
Synlett,Synthesis of the C6–C14 Fragment of Euphosalicin,"The synthesis of the C6–C14 fragment of euphosalicin, a highly oxygenated modified jatrophane diterpene, is described. Key steps in the preparation of this versatile intermediate are an Ireland–Claisen rearrangement and a Shibasaki direct asymmetric aldol reaction.",10.1055/s-0034-1380422,2015-06-19,0.6341079028521878
Angewandte Chemie International Edition,Total Synthesis of (+)-Deoxypyrrololine: A Potential Biochemical Marker for Diagnosis of Osteoporosis,"The collagen cross-link (+)-deoxypyrrololine (Dpl, 1), a potential biochemical marker for diagnosis of osteoporosis, has been obtained by a general and convergent total synthesis. The key synthetic features involve utilization of a L-glutamic acid derivative as a source for all three chiral centers in (+)-1, and construction of the pyrrole ring by condensation of an alpha-acetoxynitro compound with benzyl isocyanoacetate.",10.1002/(sici)1521-3773(19991203)38:23<3537::aid-anie3537>3.3.co;2-i,1999-12-03,0.6341040043543259
Angewandte Chemie International Edition,Total Synthesis of (+)-Deoxypyrrololine: A Potential Biochemical Marker for Diagnosis of Osteoporosis,"The collagen cross-link (+)-deoxypyrrololine (Dpl, 1), a potential biochemical marker for diagnosis of osteoporosis, has been obtained by a general and convergent total synthesis. The key synthetic features involve utilization of a L-glutamic acid derivative as a source for all three chiral centers in (+)-1, and construction of the pyrrole ring by condensation of an α-acetoxynitro compound with benzyl isocyanoacetate.",10.1002/(sici)1521-3773(19991203)38:23<3537::aid-anie3537>3.0.co;2-r,1999-11-30,0.6341040043543259
Synlett,Practical Synthesis of the Trisubstituted Naphthalene Carboxylic Acid from Neocarzinostatin Chromophore,"All articles of this category Neocarzinostatin carboxylic acid ( 5 ) has been synthesized in 33% overall yield by a nine-step sequence which is operationally easy enough to be carried out by second-year chemistry students. 3,5-dimethylanisole was brominated in the para and in one benzylic position so that an S N 2 reaction with sodium cyanide led to the cyanated aryl bromide 15 . Heck-coupling with ethyl acrylate gave the α,β-unsaturated ester 14 . It was converted into the saturated diester 18 through dissolving-metal reduction, saponification of nitrile and ester groups, and re-esterification with MeOH. Dieckmann cyclization and dehydroaromatization furnished ester 19 whose hydrolysis to the title compound 5 has been known. aromatization - Dieckmann cyclization - Heck coupling - naphthalene derivative",10.1055/s-1997-983,1997-10-01,0.6340952673540058
Journal of the American Chemical Society,Total Synthesis of Ustiloxin D,"The total synthesis of ustiloxin D, a highly potent inhibitor of microtubule assembly, has been achieved. Notable features are the use of nucleophilic aromatic substitution (SNAr) for the construction of a chiral tertiary alkyl-aryl ether linkage, Sharpless asymmetric aminohydroxylation for the formation of the beta-hydroxytyrosine moiety, macrolactamization, and regioselective methylation.",10.1021/ja017277z,2002-01-01,0.6340878268756253
Organic Letters,Efficient and Selective Synthesis of Siphonarienolone and Related Reduced Polypropionates via Zr-Catalyzed Asymmetric Carboalumination,"[reaction: see text] Siphonarienolone (1) has been synthesized from siphonarienal (3) in 66% over four steps. Synthesis of 3, in turn, has been achieved in two steps (85% combined yield) from 4, prepared from 3-buten-1-ol in seven steps (23% combined yield). Also, a two-step conversion of 3 into siphonarienone (2) is reported.",10.1021/ol0497483,2004-03-25,0.6340841070628472
Angewandte Chemie International Edition,Total Synthesis of Divergolides E and H,"This manuscript describes the first total syntheses of divergolides E and H. The route employs a telescoped hetero-Diels-Alder and oxidative carbon-hydrogen bond cleavage as an entry into the central bridged bicyclic acetal unit. Additional key steps of the highly convergent route include a desymmetrizing epoxidation, a chelation-controlled alkenylzinc addition, an amide formation between a hindered aniline and an acylating agent that is prone to ketene formation, and a challenging macrolactonization.",10.1002/anie.201810336,2018-10-12,0.6340748769679334
Tetrahedron,"1,6-dihydro-3(2H)-pyridinones as synthetic intermediates. A novel total synthesis of (±)-ibogamine and (±)-epiibogamine",,10.1016/s0040-4039(01)82048-7,1981-01-01,0.6340684378307556
Tetrahedron,Synthesis of novel tetracyclic chromenes through carbanion chemistry of 4-methyl coumarins,,10.1016/j.tetlet.2006.06.047,2006-07-04,0.6340590378672235
Journal of Organic Chemistry,"Total Synthesis of Michellamines A−C, Korupensamines A−D, and Ancistrobrevine B","Efficient syntheses of the title compounds have been developed. Several strategies for preparation of each of the naphthalene and tetrahydroisoquinoline (THIQ) portions were developed. Initial attempts to use benzyne plus furan cycloaddition reactions were thwarted by the unfavorable sense of the regiochemical outcome. An interesting annulation reaction of benzynes derived from 2,4-dibromophenol derivatives formed the core of the shortest naphthalene synthesis. An alternative annulation initiated by the addition of a benzylic sulfone anion to methyl crotonate led to an efficient naphthol synthesis amenable to large scale. The THIQ synthesis of Bringmann was used initially and subsequently complemented by a route whose key step involved the opening of N -tosyl-2-methylethyleneimine by a 3,5-dimethoxyphenylcuprate reagent. The results from a variety of aryl cross-coupling reactions are described. Suzuki coupling of the boronic acid derived from the naphthalene moiety with a THIQ-iodide was the most generally effective method for forming the hindered biaryl bond. The korupensamines and ancistrobrevine B were then revealed by deprotection. The oxidative coupling of several 4-aryl-1-naphthols to indigoids (cross ring naphthoquinones) with silver oxide effected the critical dimerization reaction needed to establish the michellamine skeleton. For the perbenzylated precursor, hydrogen over palladium on carbon both reductively bleached the indigoid and hydrogenolyzed the benzyl ethers and amines to release the free michellamines. The synthesis of several michellamine analogues, including ent -michellamines, is outlined. Results of anti-HIV assays are presented.",10.1021/jo9908187,1999-08-24,0.6340402339763102
Organic Letters,"A Catalytic, Asymmetric Formal Synthesis of (+)-Hamigeran B","A concise asymmetric, formal synthesis of (+)-hamigeran B is reported. A Pd-catalyzed, decarboxylative allylic alkylation, employing a trifluoromethylated derivative of t-BuPHOX, is utilized as the enantioselective step to form the critical quaternary carbon center in excellent yield and enantioselectivity. The product is converted in three steps to a late-stage intermediate previously used in the synthesis of hamigeran B.",10.1021/ol102669z,2011-01-27,0.6340342925203429
Angewandte Chemie International Edition,Total Synthesis of Marinomycin A Based on a Direct Dimerization Strategy,"The asymmetric total synthesis of (+)-marinomycin A, a 44-membered macrodiolide antitumor agent and antibiotic isolated from a marine actinomycete, Marinispora strain CNQ-140, is reported. The key features of the synthesis include the highly convergent stereocontrolled construction of the monomeric hydroxy salicylate starting from asymmetric epoxidation of the σ-symmetrical dialkenyl carbinol, and an unprecedented direct dimerization through NaHMDS-promoted double transesterification.",10.1002/anie.201404408,2014-06-24,0.6340088439784078
Synthesis,Synthesis of Mirabiquinone A: A Biquinone from the Sea Urchin Scaphechinus mirabilis and Related Compounds,"The first total synthesis of mirabiquinone A (2,3,5,6,8,10,11,13-octahydroxy-7-methyl-1 H -dibenzo[ b , h ]xanthene-1,4,9,12(7 H )-tetraone) produced by the sea urchin Scaphechinus mirabilis is described. This was achieved by cyclization of 6,6′-ethylidenebis(7-hydroxy-2,3-dimethoxynaphthazarin) or its mono- or dimethoxy derivatives and functional group deprotection. The synthesis of methyl analogues of mirabiquinone A is also described.",10.1055/s-0035-1560389,2016-01-20,0.6339970335201106
Synlett,"Synthesis of the H-I-J Tricyclic Fragment of Ciguatoxin, a Marine Polyether Toxin","All articles of this category During the course of our synthetic studies on ciguatoxin, synthesis of H-I-J tricyclic fragment has been stereoselectively achieved starting from a d-glucal derivative. The key steps are Sonogashira coupling reaction and cobalt complex-mediated oxocane cyclization. ciguatoxin - biscobalthexacarbonyl - oxocane cyclization - Sonogashira coupling",10.1055/s-2000-6507,2000-02-01,0.6339939375023136
Organic Letters,Synthesis of (−)-Chaetominine,The tricyclic hydroxy imidazolidinone was converted to chaetominine in seven steps in 22% overall yield. The key step was the construction of the delta-lactam by heating an amino ester with a catalytic amount of DMAP in toluene at reflux.,10.1021/ol7022483,2007-10-18,0.6339819734150282
Tetrahedron,"A new synthesis of 1,2,4-triazolin-5-ones: application to the convergent synthesis of an NK1 antagonist",,10.1016/s0040-4039(00)01548-3,2000-10-01,0.6339785756690285
Organic Letters,Indole Diterpenoid Synthetic Studies. The Total Synthesis of (+)-Nodulisporic Acid F,"[structure: see text] A stereocontrolled total synthesis of (+)-nodulisporic acid F, the simplest member of a family of novel ectoparasiticidal agents, has been achieved. Highlights of the effective modular synthetic strategy include anionic union of a tricyclic lactone with o-toluidine via our 2-substituted indole synthetic protocol, an optimized C-ring construction protocol, and a late-stage installation of the alpha,beta-unsaturated carboxylic acid side chain via the B-alkyl Suzuki-Miyaura cross-coupling tactic.",10.1021/ol060290+,2006-03-24,0.633968879734874
Tetrahedron,Practical routes toward the synthesis of 2-halo- and 2-alkylamino-4-pyridinecarboxaldehydes,,10.1016/s0040-4039(01)01428-9,2001-09-01,0.6339636722591775
Organic Letters,Exceedingly Efficient Synthesis of (±)-Grandifloracin and Acylated Analogues,A highly efficient regio- and stereoselective total synthesis of (±)-grandifloracin via a tandem dearomative epoxidation/spontaneous Diels-Alder cyclodimerization from salicylic acid in only four steps is reported. The synthetic route allows for late-stage diversification of the core structure to give ready access to analogues of this promising agent against pancreatic cancer.,10.1021/acs.orglett.5b01292,2015-06-10,0.6339171677650385
Synlett,Synthetic Studies toward Amphidinolide H1: Segment C14-C26,Stereoselective synthesis of the C14-C26 moiety of ­amphidinolide H1 is described. The key features of the approach ­include the convergent fragment assembly with a highly diastereoselective aldol reaction to establish the C18 stereochemistry and ­using commercially available chiral pool.,10.1055/s-2006-956498,2006-12-20,0.6338915494152039
Journal of Organic Chemistry,"A Convergent Route for the Total Synthesis of Malyngamides O, P, Q, and R","A convergent, enantioselective and general synthetic route to a class of marine natural products-malyngamides O (1), P (2), Q (3), R (4), 5''-epi-3 and 5''-epi-4-bearing a novel vinyl chloride structural motif was developed. The key steps involved construction of the vinyl chloride functionality by Wittig reaction, a DCC/HOBt-promoted amidation, an aldol reaction in the construction of the basic backbone of 1, 2, 3, 4, 5''-epi-3, and 5''-epi-4, and methylation of an enol moiety via either base/acid conditions or a Mitsunobu reaction. Moreover, the absolute configuration of the stereogenic center at C-5'' in 3 was further confirmed by synthesis of the natural product and its C-5'' epimer.",10.1021/jo9003103,2009-04-24,0.6338888213990845
Organic Process Research & Development,Expeditious Process Improvement for the Synthesis of RWJ-333966,We improved chemical processes for synthesizing RWJ-333966 1 and obtained this compound over five steps in 40% overall yield.,10.1021/op0601565,2006-10-21,0.6338832387362441
Organic Letters,"Synthesis of Side-Chain Locked Analogs of 1α,25-Dihydroxyvitamin D<sub>3</sub> Bearing a C17 Methyl Group","A convergent synthesis of side-chain locked vitamin D analogs 3 and 4, which bind strongly in silico to the vitamin D receptor (VDR), is described. The synthetic approach features an S N 2′- syn displacement of carbamates by cuprates to set the challenging quaternary stereogenic center at C17 and a Pd-catalyzed construction of the triene system in the presence of a diyne moiety.",10.1021/acs.orglett.8b00849,2018-04-13,0.6338563597774518
Tetrahedron,"A one-pot, efficient synthesis of the potent cytotoxic podophyllotoxin derivative NPF",,10.1016/s0040-4039(97)00450-4,1997-04-01,0.6338505871525707
Journal of Organic Chemistry,Enantioselective Total Synthesis of (+)-Nocardioazine B,"In this paper, we report an enantioselective total synthesis of (+)-nocardioazine B, a prenylated hexahydropyrrolo[2,3- b]indole (HPI) alkaloid with a central 2,5-diketopiperazine (DKP) ring. The key step in our synthetic route is a copper-catalyzed sequential arylation-alkylation of o-haloanilide derivatives. Based on this transformation, the construction of C3 all-carbon quaternary stereocenters presented in the HPI systems was achieved with high yields and excellent diastereoselectivity.",10.1021/acs.joc.8b02329,2018-11-02,0.6338504602560989
Synthesis,Stereoselective Synthesis of Cholesteryl Derivatives Bearing a Chiral Allenic Group in the Side Chain,"All articles of this category Two cholesteryl allenic stereoisomers (a S )- 11 and (a R )- 11 are prepared stereoselectively. The key step of the synthesis is the coupling of pregnenolone to the lithium salt of the optically active 5-ethynyl-1,3-dioxolane ( S )- 8 or ( R )- 8 . These two chiral synthons are obtained from the enantiomer primary alcohol ( S )- 3 and ( R )- 3 , which are prepared according to a new synthetic pathway from methyl (2 S )- and (2 R )-2,3- O -isopropylideneglycerate [(S)- 1 and (R)- 1 ].",10.1055/s-1989-27161,1989-01-01,0.633847898303542
Journal of the American Chemical Society,"A New Artificial Cyclase for Polyprenoids:  Enantioselective Total Synthesis of (−)-Chromazonarol, (+)-8-<i>e</i><i>pi</i>-Puupehedione, and (−)-11‘-Deoxytaondiol Methyl Ether","This paper describes a new artificial cyclase, optically pure 3-o-fluorobenzyloxy-2-hydroxy-2'-(p-methoxybemzyl)-1,1'-binaphthyl.SnCl4, which is effective for the enantioselective cyclization of 2-(polyprenyl)phenol derivatives to afford polycyclic terpenoids bearing a chroman skeleton such as (-)-chromazonarol, (+)-8-epi-puupehedione, a key synthetic intermediate of (+)-wiedendiol, and (-)-11'-deoxytaondiol methyl ether.",10.1021/ja0472026,2004-08-18,0.6338449426539361
Journal of Organic Chemistry,"Short, Stereoselective Synthesis of the Naturally Occurring Pyrrolidine Radicamine B and a Formal Synthesis of Nectrisine","A short, stereoselective synthesis of the naturally occurring pyrrolidine radicamine B is reported. Garner's (R)-aldehyde, prepared from D-serine, was the chiral starting material. The pyrrolidine ring was stereoselectively created in a very efficient way through a five-step, one-pot transformation. In addition, an intermediate of this synthesis was transformed into an intermediate of a previously published synthesis of the potent alpha-glucosidase inhibitor nectrisine.",10.1021/jo8012989,2008-09-03,0.6338374414492853
Journal of Organic Chemistry,Synthesis of Pentaoxa[5]peristylanes,"The synthesis of alkyl-substituted pentaoxa[5]peristylanes has been accomplished by ozonolysis of 2,3-bis-endo-7-anti-triacylnorbornenes 6a-d and by direct chemical transformation of the tetraacetal tetraoxa cages 11 and 12. Various reaction conditions have been used to optimize the overall yield for the synthesis of methyl group substituted pentaoxa[5]peristylane 7d. Ozonolysis of 6d in CDCl(3) at -78 degrees C without reduction was performed to study the ozonolysis chemistry of the triacylnorbornenes 6a-d. The synthesis of the parent (unsubstituted) compound 25 of pentaoxa[5]peristylane has been accomplished by a three-step efficient sequence with a maximum 45% overall yield via ozonolysis of the dihemiacetal 24. The structure of pentaoxa[5]peristylanes was proven by X-ray analysis of the parent compound 25. The syntheses of the triacetal tetraoxa cage 26, a new type of oxa cage, and a new entry for the synthesis of the parent compound 33 of tetraacetal tetraoxa cages were also demonstrated.",10.1021/jo982049h,1999-02-09,0.6338315756944988
Synlett,"Efficient and Convergent CouplingRoute for the Short-step Synthesis of Enantiopure 2α-and 2β-Alkylated 1α,25-Dihydroxy-19-norvitaminD<sub>3</sub>Analogues","Novel efficient synthesis of several enantio-pure 2-alkyl­ated 1α,25-dihydroxy-19-norvitamin D3 analogues through radical introduction of 2-alkyl chain and C5-C6 position coupling using Julia-type olefination as key steps was established starting from commercially available (-)-quinic acid as a chiral pool.",10.1055/s-2003-39908,2003-01-01,0.6338305793311889
Organic Letters,"Synthesis of Spiro[4.5]decane CF-Ring Analogues of 1α,25-Dihydroxyvitamin D<sub>3</sub>","A novel series of analogues of calcitriol (1) is developed featuring a spirocyclic central core resulting from C18/C21-connection and C15/C16-deletion (2a, 2b). The synthesis of the key intermediate involves an Eschenmoser rearrangement of an enantiomerically pure bromo-substituted cyclohexenol.",10.1021/ol061575p,2006-08-24,0.6338176131450272
Journal of the American Chemical Society,Protecting-Group-Free and Catalysis-Based Total Synthesis of the Ecklonialactones,"A concise and protecting-group-free total synthesis of optically pure ecklonialactones A (1) and B (2) is described. The successful route to these oxylipins isolated from various brown algae involves five transition-metal-catalyzed transformations in the longest linear sequence of 13 steps. The first chiral center was set by a rhodium-catalyzed 1,4-addition of an alkenyl boronate to the commercial butenolide 11, which was controlled by Carreira's carvone-derived diene ligand 21. Other key steps involve a ring-closing olefin metathesis effected by the ruthenium indenylidene complex 22 for the formation of the five-membered carbocycle, a vanadium-catalyzed, hydroxy-directed epoxidation, and a ring-closing alkyne metathesis (RCAM) to forge the macrocyclic ring. Because of the unusually high propensity of the oxirane of the ecklonialactones for ring-opening, this transformation was best achieved with [(Ph(3)SiO)(3)Mo[triple bond]CPh].OEt(2) (34) as the catalyst, which is a representative of a new generation of highly tolerant yet remarkably efficient molybdenum alkylidyne complexes. The ancillary triphenylsilanolate ligands in 34 temper the Lewis acidity of the molybdenum center and are not able to nucleophilically open the fragile epoxide ring. The final reduction of the cycloalkyne formed in the RCAM step to the required (Z)-alkene was accomplished either by Lindlar reduction or with the aid of nickel boride.",10.1021/ja104796a,2010-07-16,0.6338111978592689
Organic Process Research & Development,Route Design to Manufacture: Synthesis of the Heterocyclic Fragment of AZD5718 Using a Non-cryogenic Lithiation-Alkoxycarbonylation Reaction,"Route design and process development of the small nitrogen heterocycle 2·HCl, a constituent of AZD5718 ( 1 ), is described. The novel synthetic sequence to 2.HCl involves a desymmetrizing alkylation of 4-nitropyrazole, a non-cryogenic lithiation-alkoxycarbonylation, and a global reduction-cyclization. This new synthetic route was implemented in the manufacture of 2.HCl and was able to deliver over 1000 kg of product with a yield of 77% over the three stages.",10.1021/acs.oprd.0c00533,2021-03-29,0.6338082142003179
Journal of the American Chemical Society,Total Synthesis of Phorboxazole A via <i>de Novo</i> Oxazole Formation: Convergent Total Synthesis,"The phorboxazoles are mixed non-ribosomal peptide synthase/polyketide synthase biosynthetic products that embody polyketide domains joined via two serine-derived oxazole moieties. Total syntheses of phorboxazole A and analogues have been developed that rely upon the convergent coupling of three fragments via biomimetically inspired de novo oxazole formation. First, the macrolide-containing domain of phorboxazole A was assembled from C3-C17 and C18-C30 building blocks via formation of the C16-C18 oxazole, followed by macrolide ring closure involving an intramolecular Still-Genarri olefination at C2-C3. Alternatively, a ring-closing metathesis process was optimized to deliver the natural product's (2Z)-acrylate with remarkable geometrical selectivity. The C31-C46 side-chain domain was then appended to the macrolide by a second serine amide-derived oxazole assembly. Minimal deprotection then afforded phorboxazole A. This generally effective strategy was then dramatically abbreviated by employing a total synthesis approach wherein both of the natural product's oxazole moieties were installed simultaneously. A key bis-amide precursor to the bis-oxazole was formed in a chemoselective one-pot, bis-amidation sequence without the use of amino or carboxyl protecting groups. Thereafter, both oxazoles were formed from the key C18 and C31 bis-N-(1-hydroxyalkan-2-yl)amide in a simultaneous fashion, involving oxidation-cyclodehydrations. This synthetic strategy provides a total synthesis of phorboxazole A in 18% yield over nine steps from C3-C17 and C18-C30 synthetic fragments. It illustrates the utility of a synthetic design to form a mixed non-ribosomal peptide synthase/polyketide synthase biosynthetic product based upon biomimetic oxazole formation initiated by amide bond formation to join synthetic building blocks.",10.1021/ja1089099,2010-12-29,0.6338047497156255
Journal of the American Chemical Society,Total Synthesis of (−)-Sarain A,"This article describes the details of our synthetic studies toward the complex marine alkaloid sarain A. Various strategies were conceived, setbacks encountered, and solutions developed, ultimately leading to a successful enantioselective total synthesis. Our route to (+)-sarain A features a number of key steps, including an asymmetric Michael addition to install the C4'-C3'-C7' stereotriad, an enoxysilane-N-sulfonyliminium ion cyclization to set the C3 quaternary carbon stereocenter, and assemble the diazatricycloundecane core, a ring-closing metathesis to construct the 13-membered ring, an intramolecular Stille coupling to fashion the unsaturated 14-membered macrocycle, and a late-stage installation of the tertiary amine-aldehyde proximity interaction.",10.1021/ja074300t,2007-09-12,0.6338032474967621
Journal of Organic Chemistry,Enantioselective Synthesis of Marine Indole Alkaloid Hamacanthin B,"An enantioselective total synthesis of hamacanthin B (1) is described. This synthesis is based on the asymmetric synthesis of (S)-2-azido-(indol-3-yl)ethylamine 7, which is coupled with the 3-indolyl-alpha-oxoacetyl chloride 8 and subsequently used in a successful intramolecular Staudinger-aza Wittig cyclization to form the central dihydropyrazinone ring. The stereochemistry of naturally isolated hamacanthin B is revealed as the (S)-configuration.",10.1021/jo0108109,2002-01-24,0.6337965076715741
European Journal of Organic Chemistry,Total Synthesis of Calystegine B<sub>4</sub>,Abstract The total synthesis of calystegine B 4 was achieved in 10 steps from (–)‐ D ‐lyxose by using a new synthetic strategy to obtain the requisite protected hydroxylated 4‐aminocyclohept‐2‐en‐1‐one without the problem of regioisomer formation that was a problem in the earlier synthesis of this natural product. The key steps included a Petasis–borono‐Mannich reaction and a ring‐closing metathesis reaction.,10.1002/ejoc.201000157,2010-05-04,0.6337886762788408
Journal of Organic Chemistry,"Synthesis of 2,3-Dinor-5,6-dihydro-15F<sub>2t</sub>-isoprostane","A concise synthesis of the 15-F 2t -isoprostane urinary metabolite 2, a potential marker for systemic oxidative stress, is described. This synthesis confirmed the structure of this important product of human metabolism. The key transformation is the rhodium-mediated diastereoselective cyclization of diazo ketone 4, followed by cyclopropane ring opening with thiophenol and Lewis acid. Material prepared by the synthesis outlined here will be used to develop an antibody-based assay for clinically quantifying systemic oxidative stress.",10.1021/jo9910738,1999-09-21,0.6337788199786799
Journal of Organic Chemistry,Investigation of a Highly Selective Asymmetric Synthesis Strategy for <i>cis</i>-2-Fluorocyclopropanecarboxylic Acid: The Key Component of Sitafloxacin,"-2-fluorocyclopropanecarboxylic acid with excellent stereoselectivity and regioselectivity was developed from commercially available starting materials, namely, fluoromethylphenylsulfone and chiral glycidyl derivatives, on a 100 g scale at the start. Despite the high overall yield, the synthetic route is remarkable for its brevity. This strategy forms the basis for further production of sitafloxacin on an industrial scale and provides an affordable and high-quality product.",10.1021/acs.joc.4c02299,2024-11-27,0.6337504072432069
Journal of the American Chemical Society,Applications of Vinylogous Mannich Reactions. Concise Enantiospecific Total Syntheses of (+)-Croomine,"Because the vinylogous Mannich reaction of substituted furans with iminium ions is a useful construction in alkaloid synthesis, it is important to know what effects substituents on the two reacting partners have upon the stereoselectivity of the reaction. Toward this end, the additions of the methylated furans 9a − h to the iminium ion generated in situ from the ethoxy carbamate 10 were examined. Generally, mixtures (3−24:1) of the threo and erythro adducts 11a − h and 12a − h were obtained in 50−96% combined yields, with the threo isomers being the major products. Two extraordinarily concise asymmetric syntheses of (+)-croomine ( 1 ) have been completed using a novel strategy, highlighted by two vinylogous Mannich reactions as key constructions. The first such reaction involved the addition of 5-(4-bromobut-1-yl)-3-methyl-2-(triisopropylsilyloxy)furan to the N -acyliminium salt derived from the l -pyroglutamic acid derivative 17 to give the adduct [5( S ),2‘( S ),5‘( S )]-5-(4‘ ‘-bromobut-1‘ ‘yl)-5-[ N -( tert -butoxycarbonyl)-2‘-(methoxycarbonyl)-pyrrolidin-5‘-yl]-3-methyl-2(5 H )-furanone ( 18 ) as the major product. Refunctionalization of 18 led to the tricyclic intermediate [3‘ S -[3‘α,9‘α( S *),9‘aα]]-decahydro-4-methyl-5-oxospiro[furan-2(3 H ),9‘-[9 H ]pyrrolo[1,2- a ]azepin]-3‘-carboxylic acid, hydrobromide salt, which was, in turn, converted to an iminium salt that underwent a second vinylogous Mannich reaction to give [3‘ S -[3‘α( R *),9‘α( S *),9‘aα]]-3‘-(2,5-dihydro-4-methyl-5-oxo-2-furanyl)decahydro-4-methylspiro[furan-2(5 H ),9‘-[9 H ]pyrrolo[1,2- a ]azepin-5-one ( 24 ) as the major adduct. Stereoselective reduction of the unsaturated lactone 24 gave 1, completing a synthesis that required a total of only 11 chemical steps from commercially available starting materials. In a second approach, the initial Mannich adduct [5( S ),2‘( S ),5‘( S )]-5-(4‘ ‘-bromobut-1‘ ‘-yl)-5-[2‘-(methoxycarbonyl)pyrrolidin-5‘-yl]-3-methyl-2(5 H )-furanone was transformed into the unsaturated tricyclic intermediate [3‘ S -[3‘α( R *),9‘α( S *),9‘aα]]-3‘-(2,5-dihydro-4-methyl-5-oxo-2-furanyl)-1‘,2‘,3‘,5‘,6‘,7‘,8‘-octahydro-4-methylspiro[furan-2(5 H ),9‘-[9 H ]pyrrolo[1,2- a ]azepin]-5-one, which underwent hydrogenation to give 1 as the only isolable product, thereby completing a synthesis that required only 10 steps.",10.1021/ja990077r,1999-07-14,0.633741859115213
Tetrahedron,Radical-initiated cyclization as a key step for the synthesis of oxoprotoberberine alkaloids,,10.1016/j.tetlet.2009.05.095,2009-05-31,0.6337359958207613
Journal of the American Chemical Society,"Enantioselective Total Syntheses of (+)-Castanospermine, (+)-6-Epicastanospermine, (+)-Australine, and (+)-3-Epiaustraline","The total syntheses of the potent glycosidase inhibitors castanospermine ((+)- 1 ), 6-epicastanospermine ((+)- 2 ), australine ((+)- 3 ), and 3-epiaustraline ((+)- 4 ) are described. The syntheses of indolizidine alkaloids (+)- 1 and (+)- 2 were accomplished in eight steps and in 18% and 24% overall yields from 2,5-dihydrofuran while the pyrrolizidine alkaloids (+)- 3 and (+)- 4 were obtained in a nine-step sequence in 17% and 22% overall yields from the same starting material. These four natural products are derived from a single common intermediate, nitroso acetal (−)- 31, which is created in the key step by the asymmetric tandem [4 + 2]/[3 + 2] cycloaddition between silaketal nitro olefin 18 and chiral vinyl ether (+)- 23 . The ability to access both 5,5- and 5,6-fused bicyclic systems was a result of a successful in situ N-alkylation strategy during the hydrogenolysis of four highly functionalized nitroso acetals. A novel silaketal tether provided exceptional levels of diastereocontrol and the ideal combination of protection and functional-group placement for the tandem nitroalkene cycloaddition process.",10.1021/ja9829970,1999-03-23,0.6337306166505491
Journal of the American Chemical Society,"Domino Michael/Mannich/<i>N</i>-Alkylation Route to the Tetrahydrocarbazole Framework of Aspidosperma Alkaloids: Concise Total Syntheses of (−)-Aspidospermidine, (−)-Tabersonine, and (−)-Vincadifformine","We report a novel, asymmetric domino Michael/Mannich/N-alkylation sequence for the rapid assembly of the tetrahydrocarbazole framework of Aspidosperma alkaloids. This method was utilized in the concise total syntheses of classical targets (-)-aspidospermidine, (-)-tabersonine, and (-)-vincadifformine in 10 or 11 steps. Additional key steps include ring-closing metathesis to prepare the D-ring and Bosch-Rubiralta spirocyclization to prepare the C-ring.",10.1021/ja408114u,2013-08-23,0.633719276443534
Organic Process Research & Development,Optimisation of Permanganate Oxidation and Suzuki−Miyaura Coupling Steps in the Synthesis of a Na<sub>v</sub>1.8 Sodium Channel Modulator,"The development is described of a viable kilo-scale synthesis of the Na v 1.8 sodium channel modulator, N -methyl-6-amino-5-(2,3,5-trichlorophenyl)pyridine-2-carboxamide (PF-1247324) in five steps, starting from 6-amino-5-bromo-2-picoline, in 33% overall yield. Two key steps required significant optimisation to improve yield and reproducibility. Oxidation of 6-acetamido-5-bromo-2-methylpyridine by permanganate to give the corresponding carboxylic acid derivative was improved by adding potassium dihydrogen phosphate, which moderated the reaction mixture pH and doubled the yield. The potassium fluoride-promoted Suzuki−Miyaura coupling between 2,4,5-trichlorophenylboronic acid and methyl 6-amino-5-bromopyridine-2-carboxylate, catalysed by tri( tert -butyl)phosphinepalladium (0), proceeded reliably to completion at room temperature in high yield when water was added. Anhydrous reaction mixtures reacted much more slowly, and ‘wet’ mixtures led to significant proto-deboronation in the absence of sufficient active catalyst. In the final step, amidation of the ester with methylamine gave PF-1247324.",10.1021/op900092h,2009-07-24,0.6337170752630382
Synlett,"Total Synthesis of Stevastelin B, a Novel Immunosuppressant","All articles of this category Total synthesis of stevastelin B is described. Evans asymmetric aldol methodology and Roush asymmetric allylation were used to construct four consecutive stereo-centers on the octadecanoic acid moiety of stevastelin B. Subsequent coupling with a dipeptide and macrolactamization gave stevastelin B. The flexibility of this route could allow the synthesis of many analogues for biological tests, which cannot be obtained from natural sources. total synthesis - stevastelin B - immunosuppressant - asymmetric aldol reaction - asymmetric allylation",10.1055/s-2001-13382,2001-12-31,0.6337094029013558
Organic Letters,Asymmetric Synthesis of 10-Demethoxyvincorine Enabled by Dual Ni/Ti-Catalyzed Reductive Cyclization,"Herein, we report the asymmetric synthesis of 10-demethoxyvincorine in 12 steps. The synthesis is highlighted by several key transformations: (1) a Pd-catalyzed Catellani-type reaction for the preparation of C2-alkylated tryptamine, (2) a chiral phosphoric acid (CPA)-catalyzed asymmetric bromocyclization to construct enantioenriched 3a-bromo-hexahydropyrroloindoline, (3) a dual Ni/Ti-catalyzed reductive cyclization to establish the bridged ring system, and (4) a SmI 2 -promoted reductive cyclization to forge the strained E-ring.",10.1021/acs.orglett.5c00982,2025-04-10,0.6337007924906826
Synlett,Synthetic Studies on Plakinidines,A synthetic route to the pentacyclic core of the plakinidines was developed. Our synthesis features the construction of the fused heterocycles (the A and the E rings) by the formation of carbon–nitrogen bonds using carbonyl functions prior to the late-stage aromatization of the B ring.,10.1055/s-0034-1380689,2015-04-30,0.6336956123952938
Tetrahedron,"Asymmetric synthesis and absolute stereochemistry of cholesterol absorption inhibitor, SCH 48461",,10.1016/0040-4039(94)85308-8,1994-10-01,0.6336934978815828
Tetrahedron,an intermediate for the total synthesis of guaianolides; A correlation,,10.1016/s0040-4039(00)81816-x,1983-01-01,0.6336853120136706
Tetrahedron,Total synthesis of prostaglandins E2 and F2α () via a tricarbocyclic intermediate,,10.1016/s0040-4039(00)61815-4,1970-01-01,0.6336853120136706
Tetrahedron,An intermediate for the total synthesis of guaianolides,,10.1016/s0040-4039(00)88348-3,1982-01-01,0.6336853120136706
Synlett,"En Route to New Chiral Ferrocene Derivatives: Dead Ends, Detours, and Avenues","The enantioselective synthesis of ?-amino-?-ferrocenyl alcohols, a new class of chiral ferrocene derivatives suitable for the elaboration of auxiliaries and ligands for asymmetric synthesis, can be efficiently achieved by the catalytic asymmetric dihydroxylation of 1-ferrocenylalkenes, followed by the regio- and stereoselective substitution of the hydroxy group adjacent to the ferrocene moiety by nitrogen nucleophiles. En route to these compounds, several previously unknown metallocene derivatives such as ?-ferrocenyl epoxides, interannularly cyclopalladated ferrocenyloxazolines, and ?-amino-?-ferrocenyl acids have been obtained. The first examples of an organocatalytic approach to the enantioselective synthesis of chiral ferrocenes are also presented.",10.1055/s-0029-1217514,2009-06-23,0.6336736775584926
Organic Process Research & Development,Application of the Schöpf Method to Optimization of the Synthesis of 3-[2-(<i>p</i>-<i>N</i>-Acetylaminophenyl)ethyl]-3-hydroxy-4-methylpentanoic Acid:  Simultaneous Reduction of Three Functional Groups to Maximize Yield and Throughput,"Application of the Schöpf method to development of a high yield condensation process to prepare a labile β-( p -nitrophenyl)-α,β-unsaturated ketone system, along with development of a procedure for simultaneous hydrogenation/hydrogenolysis of olefin, benzyl ester, and nitro groups, allows the construction of an inexpensive route to 3-[2-( p - N -acetylaminophenyl)ethyl]-3-hydroxy-4-methylpentanoic acid, a key intermediate in the preparation of CI-1029 and related HIV protease inhibitors.",10.1021/op000206k,2000-10-21,0.6336720817151722
Synthesis,A Selective Synthesis of (<i>E</i>)-2-Methyl-1-alkenyl Iodides via Zirconium-Catalyzed Carboalumination,,10.1055/s-1979-28729,1979-01-01,0.6336682367169565
European Journal of Organic Chemistry,Towards the Synthesis of (–)‐Callipeltoside A: Stereoselective Synthesis of the C1–C14 Macrolactone Core,"Abstract A highly stereoselective synthesis of the C1–C14 macrolactone core of the cytotoxic macrolide (–)‐callipeltoside A has been achieved by utilizing an anti ‐selective aldol reaction and Wittig olefination to introduce an ( E )‐trisubstituted alkene, chemoselective diisobutylaluminum hydride (DIBAL‐H) reduction of the 2,3‐epoxy tosylate to install the C13 stereocenter, and intramolecular trapping of the acyl‐ketene intermediate by the C13 hydroxy group as key steps.",10.1002/ejoc.201101635,2012-02-10,0.6336670868352168
Synthesis,An Asymmetric Synthesis of (-)-Tetrahydrolipstatin,All articles of this category A key step in a short asymmetric synthesis of the potent pancreatic lipase inhibitor (-)-tetrahydrolipstatin (2) is a Lewis acid-catalysed [2+2] cycloaddition of n -hexyl(trimethylsilyl)ketene (5) to ( R ) -3-( tert -butyldimethylsilyloxy)tetradecanal (4a) .,10.1055/s-1994-25684,1994-01-01,0.6336668851181504
Tetrahedron,The reaction of erythromycin hydrazone with nitrous acid a new route to erythromycylamine,,10.1016/s0040-4039(01)84230-1,1972-01-01,0.6336585437657423
European Journal of Organic Chemistry,Radical Cyclizations in the Synthesis of 3‐Methyl‐<i>cis</i>‐octahydroindol‐5‐ones,"Three approaches to the stereoselective synthesis of 3‐methyl‐ cis ‐octahydroindoles through a 5‐ endo ‐ trig radical cyclization are described. First, starting from an N ‐vinyl‐α‐chloroacetamide, the cyclization was followed by lactam methylenation and hydrogenation. Second, starting from an alkyne‐tethered enamide, the cyclization was promoted by Bu 3 SnH, and this was followed by protonolysis of the vinylstannane and hydrogenation of the exocyclic alkene. Third, through a 2,2‐dichloropropanamide cyclization onto an alkenyl bond, and hydrogenation of the resulting endocyclic double bond; this represents the most efficient sequence to form the target compounds. 1,5‐Enyne cyclizations through a 5‐ endo ‐ trig process are reported. Here, a remote functional group (ketal or ketone), allowed the diastereoselectivity of the octahydroindole ring formation to be reversed through steric control of the facial selectivity in the hydrogen radical delivery step.",10.1002/ejoc.201700086,2017-03-09,0.6336573136674146
Angewandte Chemie International Edition,Total Synthesis of Lactonamycinone,"A revised strategy was required for the installation of the remaining polyoxygenated E and F rings of lactonamycinone (2). Key features in the successful route include dihydroxylation of a ketoquinone, the use of a furanone as a lactone surrogate (see 1), and an acid-induced ketalization reaction to install the angular methoxy substituent.",10.1002/anie.200352592,2003-11-18,0.6336353953017716
Angewandte Chemie International Edition,"Total Synthesis of Macrolactin A with Versatile Catalytic, Enantioselective Dienolate Aldol Addition Reactions","A highly convergent total synthesis of macrolactin A (1) utilizes modern asymmetric catalytic C-C coupling methods. The longest linear sequence in the route is 16 steps with an average yield of 86% per step. This total synthesis is valuable, because 1, which has been shown to possess activity against HIV, is not readily accessible from its natural source, a taxonomically unclassified deep-sea bacterium.",10.1002/(sici)1521-3773(19980518)37:9<1261::aid-anie1261>3.0.co;2-2,1998-05-18,0.6336321965731749
Organic Process Research & Development,Some Items of Interest to Process R&amp;D Chemists and Engineers,"The incidence of systemic fungal infections has increased in recent decades.The major antifungal therapeutic reagents for the treatment of systemic fungal infections, including the polyenes, azoles, and echinocandins, are often limited by their side effects, clinical resistance, and a narrow spectrum of antifungal activity.The natural product enfumafungin, isolated from a fermentation of Hormonema sp., is capable of inhibiting fungal glucan synthase.As part of an ongoing drug discovery program at Merck Research Laboratories, two novel enfumafungin derivatives, 1 and 2, were identified as potent glucan synthase inhibitors and selected for further development.Now Zhong and co-workers at Merck Process Research describe an efficient and scalable semisynthesis of glucan synthase inhibitors 1 and 2 starting from the fermentation product enfumafungin (J.Org.Chem.2012, 77, 3297).The highlights of the synthesis include a high-yielding ether bond-forming reaction between a sterically demanding sulfamidate and alcohol and a remarkably chemoselective palladium(II)-mediated Corey-Yu allylic oxidation at the highly congested C-12 position of the enfumafungin core.Multihundred gram quantities of these challenging target drug candidates 1 and 2 were prepared, in 12 linear steps with 25% isolated yield and 13 linear steps with 22% isolated yield, respectively.■ A RING-CLOSING METATHESIS STRATEGY FOR THE SYNTHESIS OF HCV PROTEASE INHIBITOR VANIPREVIR (MK-7009) Chronic infection with hepatitis C virus (HCV) is a worldwide epidemic, affecting approximately 180 million individuals around the globe.The launch of two new drugs, Boceprevir andTelaprevir, shows promise to improve the success rate in HCV therapy.Despite these tremendous accomplishments, additional improvements in the area of genotype coverage, drug dose, and cure rate are still desired.Vaniprevir (MK-7009) is a potent HCV NS3/4a protease inhibitor that is being evaluated for the treatment of HCV at the late stage of clinical studies.To ensure the supply of the drug for ongoing clinical studies, a chemical process amenable to production of multikilogram quantities of MK-7009 was required.A highly efficient synthesis of Vaniprevir (MK-7009) is reported by Kong, Chen and co-workers at Merck Process Research has been accomplished in nine linear steps and 55% overall yield (J. Org.Chem.2012, 77, 3820).The key features of this synthesis include a cost-effective synthesis of the isoindoline subunit and efficient construction of the 20membered macrocyclic core of Vaniprevir (MK-7009) utilizing ring-closing metathesis technology.A practical and volume efficient ring-closing metathesis protocol was achieved via simultaneous slow addition of the ruthenium catalyst (0.2 mol % loading) and the diene substrate at a concentration of 0.13 M. ■ REGIOSELECTIVITY IN THE IODINATION OF ANILINES WITH NISThe electrophilic iodination of anilines has a long history, featuring a myriad of reagents.Typically, para-substitution dominates, and attempts to change this selectivity have been based primarily on N-directed ortho-metalation strategies.However, orthoiodination can be quite competitive, even in the case of aniline itself, raising the question whether regiocontrol might be attained by simple alteration of reaction conditions.Studies toward this",10.1021/op300157d,2012-07-03,0.633618283097457
Journal of Organic Chemistry,Enantioselective Allyltitanations and Metathesis Reactions. Application to the Synthesis of Piperidine Alkaloids (+)-Sedamine and (−)-Prosophylline,"An enantioselective synthesis of the piperidine alkaloids (+)-sedamine and (-)-prosophylline is reported. The synthesis of (+)-sedamine has been achieved in 12 steps with an overall yield of 20% from benzaldehyde, and (-)-prosophylline was obtained in 15 steps with an overall yield of 9.2%, starting from D-glyceraldehyde acetonide 14. The key steps are enantioselective allyltitanation reactions and ring-closing or cross-metathesis reactions.",10.1021/jo010653d,2002-01-22,0.6336005012463791
Organic Letters,Synthetic Studies on Altemicidin:  Stereocontrolled Construction of the Core Framework,"The stereoselective synthesis of the key intermediate for altemicidin has been accomplished. The synthesis commenced with a bicyclo[3.3.0] framework, which was readily obtained via an intramolecular C-H insertion reaction. A Curtius rearrangement was employed as a key step to stereoselectively construct the beta-hydroxyl alpha-disubstituted-alpha-amino acid structure. Synthesis of vinylogous urea was achieved using hydrolysis of nitrile intermediate.",10.1021/ol701940f,2007-12-15,0.6335865449488274
Tetrahedron,"Stereoselective synthesis of methyl 3α-ethyl-1,2,3,4,6,7,12,12bβ-octahydroindolo[2,3-a]quinolizine-1α-carboxylate: A key intermediate for the preparation of tacamine-type indole alkaloids",,10.1016/0040-4039(96)00052-4,1996-02-01,0.6335805636320754
Journal of the American Chemical Society,Ruthenium-Catalyzed Alder Ene Type Reactions. A Formal Synthesis of Alternaric Acid,"Alternaric acid, a nanomolar fungal germination inhibitor, is typified by a 1,4-diene, consisting of a terminal methylene and an ( E )-1,2-disubstituted alkene. A new strategy for the synthesis of natural products containing such functionality stems from the development of a ruthenium-catalyzed addition of terminal alkenes with terminal alkynes. The alkyne substrate, 4-pentynoic acid, is commercially available or can be prepared in two steps by alkylation of tert -butyl acetate. The alkene substrate is prepared from commercially available ( S )-2-methyl-1-butanol. This synthesis involves formation of a geometically defined trisubstituted alkene by involving Pd-catalyzed cross-coupling and asymmetric dihydroxylation. The ruthenium-catalyzed coupling proceeds best in the absence of alcohol protecting groups to maximize regioselectivity. The examples of this addition illustrated herein help elucidate some of the important factors controlling regioselectivity. They also illustrate the excellent chemoselectivity. The acyclic unit of alternaric acid, which is simply coupled to a dihydropyrone fragment to complete the synthesis, is available in only 11 steps and 27% overall yield compared to the one extant synthesis also starting from ( S )-2-methyl-1-butanol which proceeds in 26 steps and 0.003% overall yield. This new reaction provides a powerful tool in streamlining this synthesis and should prove more generally useful.",10.1021/ja981540n,1998-08-29,0.633575713411917
Tetrahedron,Asymmetric synthesis of the ab-ring of aklavinone,,10.1016/0040-4039(91)80561-j,1991-12-01,0.6335654346346864
Tetrahedron,"Scalable route to high-purity 17-Amino-10-oxo-3,6,12,15-tetraoxa-9-azaheptadecanoic acid, an intermediate for therapeutic peptide synthesis",,10.1016/j.tetlet.2025.155730,2025-07-04,0.6335480539906272
Journal of the American Chemical Society,A General Iridium-Catalyzed Reductive Dienamine Synthesis Allows a Five-Step Synthesis of Catharanthine via the Elusive Dehydrosecodine,"A new reductive strategy for the stereo- and regioselective synthesis of functionalized isoquinuclidines has been developed. Pivoting on the chemoselective iridium(I)-catalyzed reductive activation of β,γ-unsaturated δ-lactams, the efficiently produced reactive dienamine intermediates readily undergo [4 + 2] cycloaddition reactions with a wide range of dienophiles, resulting in the formation of bridged bicyclic amine products. This new synthetic approach was extended to aliphatic starting materials, resulting in the efficient formation of cyclohexenamine products, and readily applied as the key step in the shortest (five-step) total synthesis of vinca alkaloid catharanthine to date, proceeding via its elusive biosynthetic precursor, dehydrosecodine.",10.1021/jacs.1c04980,2021-07-13,0.6335366405338176
Journal of Organic Chemistry,An Enantioselective Approach to Functionalized Amino Acids: Total Synthesis of Antiepileptic Drug (<i>R</i>)-Lacosamide,A short and highly efficient synthetic approach to enantiopure functionalized amino acids (FAAs) 1 skeleton from racemic butadiene monoepoxide as a starting material and its application to the total synthesis of an antiepileptic drug (R)-lacosamide 2 are described. The synthesis utilizes the palladium catalyzed Trost's Dynamic Kinetic Asymmetric Transformation (DYKAT) as key step.,10.1021/acs.joc.5b00480,2015-03-23,0.6335103028673196
Organic Letters,Concise and Stereocontrolled Synthesis of the Tetracyclic Core of Daphniglaucin C,"The tetracyclic core of daphniglaucin C was prepared from the known 4-keto-N-Boc methyl-l-prolinate in 15 steps with a cumulative yield of 14.7%. The key steps toward this core motif feature a reductive double bond transposition from an unactivated tertiary allylic alcohol, a Pd-catalyzed Stille coupling, and Dieckmann cyclizations.",10.1021/ol4018112,2013-07-26,0.6335086169076024
Synthesis,Total Synthesis of 2-Tetraprenylbenzoquinol and -benzoquinone,All articles of this category The total synthesis of 2-tetraprenylbenzoquinol and -benzoquinone is described. A key step in this synthesis is the highly regio- and stereoselective coupling between an appropriate aromatic allylcarbonate and an activated bifunctional farnesyl derivative using Pd(PPh 3 ) 4 as catalyst.,10.1055/s-1994-25555,1994-01-01,0.633500251283117
European Journal of Organic Chemistry,Synthesis of the Azaoxoaporphine Alkaloid Sampangine and Ascididemin‐Type Pyridoacridines through TMPMgCl·LiCl‐Mediated Ring Closure,"Abstract We report the synthesis of the azaoxoaporphine alkaloid sampangine ( 4 ) and a series of ring A analogues and isomers of the marine pyridoacridine alkaloid ascididemin ( 2 ). This approach starts from readily available 1‐bromo[2,7]naphthyridine ( 12 ) or 4‐bromobenzo[ c ][2,7]naphthyridine ( 5 ), and the ring A scaffold bearing an ester moiety is introduced by a Suzuki or Negishi cross‐coupling reaction. The final cyclization step was achieved through a directed remote ring metallation with the Knochel–Hauser base (TMPMgCl · LiCl; TMP = 2,2,6,6‐tetramethylpiperidinyl), followed by intramolecular trapping of the ester group.",10.1002/ejoc.201403502,2015-01-14,0.6334864992786635
Tetrahedron,Diastereoselective synthesis of a key intermediate for the preparation of tricyclic β-lactam antibiotics,,10.1016/s0040-4039(99)00929-6,1999-07-01,0.6334462864907616
Organic Process Research & Development,"Toward a Practical, Nonenzymatic Process for Investigational COVID-19 Antiviral Molnupiravir from Cytidine: Supply-Centered Synthesis","A scalable four-step synthesis of molnupiravir from cytidine is described herein. The attractiveness of this approach is its fully chemical nature involving inexpensive reagents and more environmentally friendly solvents such as water, isopropanol, acetonitrile, and acetone. Isolation and purification procedures are improved in comparison to our earlier study as all intermediates can be isolated via recrystallization. The key steps in the synthesis, namely, ester formation, hydroxyamination, and deprotection were carried out on a multigram scale to afford molnupiravir in 36-41% yield with an average purity of 98 wt % by qNMR and 99 area% by HPLC.",10.1021/acs.oprd.1c00219,2021-12-09,0.6334354176023972
Synthesis,An Efficient Synthesis of Dimethylmaleic Anhydride,"A facile three-step synthesis of dimethylmaleic anhydride (8) with 74% overall yield has been described starting from maleimide 1, via methylmaleimide 4, using two Wittig reactions followed by an alkaline hydrolysis.",10.1055/s-2002-28519,2002-01-01,0.6334335865615452
Journal of Organic Chemistry,"A Short, Efficient Copper-Mediated Synthesis of 1α,25-Dihydroxyvitamin D<sub>2</sub> (1α,25-Dihydroxyergocalciferol) and C-24 Analogs<sup>1</sup><sup>,</sup><sup>2</sup>","Two synthetic routes to the nonnatural hormone 1α,25-dihydroxyergocalciferol [ 2b, 1α,25-(OH) 2 -D 2 ] and analogs modified at C-24 have been developed both starting from aldehyde 7b . Key steps in route A (eight steps, ≈38% overall yield from 7b ) are (1) stereoselective addition of ( E )-vinyllithium reagent 8c to aldehyde 7b; and (2) S N 2‘ anti -displacement of the allylic phosphate of 5e by organocuprates derived from Grignard reagents and CuCN in the presence of LiCl. Key steps in route B (eight steps from 7b, 48% overall yield) are (1) Wittig−Horner type coupling between ketone 22, which bears an allylic phosphate group on the side chain, and the ylide derived from the Lythgoe−Roche phosphine oxide to form the vitamin D triene unit; and (2) efficient S N 2‘ anti -displacement of the phosphate group of 23 by the organocuprate derived from MeMgCl, CuCN, and LiCl, without affecting the labile vitamin D triene system, to give, after deprotection, 1α,25-(OH) 2 -D 2 . Route B is particularly attractive as an approach to diverse C-24 vitamin D analogs for biological screening.",10.1021/jo970604u,1997-09-01,0.6334252132504729
Organic Letters,Modular and Divergent Syntheses of Protoberberine and Protonitidine Alkaloids,"A modularly convergent and divergent strategy was established for the family synthesis of both protoberberine and protonitidine alkaloids. The robust, scalable, and flexible synthetic route featured a collective preparation of protoberberine and protonitidine alkaloids from a common isoquinoline assembled from pyridyne as the key synthon, which was based on the selective N-C or C-C cyclization via distinct processes. Through the strategy, 20 protoberberine alkaloids, 5 protonitidine alkaloids, and 11 analogues with diverse substituents were comprehensively aquired.",10.1021/acs.orglett.0c04310,2021-02-08,0.6334247711481046
Tetrahedron,An amide orthoesterification route to N-(1′-alkylthioglucopyranosyl)indoles,,10.1016/j.tetlet.2005.09.135,2005-10-11,0.6334071275469542
Synlett,Formal Synthesis of Kanamienamide,"A formal total synthesis of the anticancer natural product kanamienamide has been accomplished. This communication describes two approaches to the macrocyclic core of the natural product. The key features of the route include an efficient macrolactamization, a Corey–Bakshi–Shibata asymmetric reduction, and a Stork–Zhao–Wittig olefination.",10.1055/s-0036-1591929,2018-02-12,0.6333605072259308
Angewandte Chemie International Edition,Enantioselective Total Syntheses of Pallambins A–D,"The first enantioselective total syntheses of (-)-pallambins A-D have been achieved in 15 or 16 steps from a known chiral cyclohexenone. Salient features of the syntheses include a palladium-catalyzed oxidative cyclization to assemble the [3.2.1]bicyclic moiety, an Eschenmoser-Claisen rearrangement/lactone formation sequence to construct the C ring, an intramolecular Wittig reaction to form the D ring, and individual transformations of pallambins C and D to generate pallambins A and B. The described synthesis avoids protecting-group manipulations through the design of highly chemo- and stereoselective transformations. During the course of this work, a palladium-catalyzed method for the dehydrobromination of α-bromoketones was developed, and the scope of this transformation was also investigated.",10.1002/anie.201907523,2019-07-16,0.6333581628010309
Synthesis,Stereoselective Isoquinoline Alkaloid Synthesis with New Diselenides,All articles of this category The synthesis of improved optically active selenium compounds for electrophilic additions to C=C double bonds is described. These reagents allow the formation of methoxyselenenylated products with high diastereoselectivities (up to 93% de). Intramolecular aminoselenenylations with chiral selenium electrophiles provide a short route to tetrahydroisoquinoline alkaloids. asymmetric synthesis - chiral diselenides - chirality - isoquinoline alkaloids - selenium,10.1055/s-1998-2011,1998-02-01,0.6333434005278294
Organic Letters,"Synthetic Studies toward Mannopeptimycin-E:  Synthesis of the <i>O</i>-Linked Tyrosine 1,4-α,α-<i>manno,manno</i>-Pyranosyl Pyranoside","[structure: see text] The enantioselective synthesis of the C-4' acylated 1,4-alpha,alpha-manno,manno-disaccharide fragment of mannopeptimycin-E has been achieved in seven steps from d-tyrosine. The route relies upon diastereoselective palladium-catalyzed glycosylation, diastereoselective reduction, and diastereoselective bis-dihydroxylation. The efficiency of the synthesis is demonstrated by the high overall yield (37%) and the preparation of various analogues.",10.1021/ol060254a,2006-03-21,0.6333379318302311
Tetrahedron,Chiral synthesis of the def-ring system of nogalamycin,,10.1016/s0040-4039(00)98139-5,1985-01-01,0.6333359467917115
Tetrahedron,Chiral synthesis of the ABC-ring system of quinocarcin,,10.1016/s0040-4039(00)70714-3,1989-01-01,0.6333359467917115
Tetrahedron,Chiral synthesis of the ABE-ring system of quinocarcin,,10.1016/s0040-4039(00)82331-x,1988-01-01,0.6333359467917115
Journal of the American Chemical Society,Total Synthesis of Dolabelide D,"The first total synthesis of dolabelide D (or of any of the closely related dolabelides) has been achieved with a longest linear sequence of 17 steps. Key features of the synthesis include an application of the catalytic asymmetric silane alcoholysis, the tandem silylformylation-crotylsilylation, and a Brook-like 1,4-carbon to oxygen silyl migration.",10.1021/ja058692k,2006-02-09,0.633319291985729
Tetrahedron,"A highly efficient practical method for the synthesis of chiral polyhydroxy-(E,E)-1-chlorodienols and (E)-5-hydroxy enynes",,10.1016/s0040-4039(97)00907-6,1997-06-01,0.6333176267711405
Organic Letters,Total Synthesis of Nigellicine and Nigeglanine Hydrobromide,[reaction: see text] The first syntheses of the pyridazinoindazolium alkaloids nigellicine and nigeglanine hydrobromide via a common intermediate are described. Ortho-lithiation/acylation and the direct amination of an isatin ring system are the key steps in the synthesis.,10.1021/ol050769m,2005-05-19,0.6332989364029167
Organic Letters,"Total Synthesis of (−)-Picrinine, (−)-Scholarisine C, and (+)-5-β-Methoxyaspidophylline","The first asymmetric total synthesis of three picrinine-type akuammiline alkaloids, (-)-picrinine, (-)-scholarisine C, and (+)-5-β-methoxyaspidophylline, has been accomplished. The synthesis features an efficient acid-promoted oxo-bridge ring-opening and further carbonyl O-cyclization to assemble the furoindoline scaffold, an unusual Dauben-Michno oxidation to construct the requisite α,β-unsaturated aldehyde functionality, and a nickel-mediated reductive Heck reaction to forge the [3.3.1]-azabicyclic core.",10.1021/acs.orglett.1c02393,2021-08-19,0.6332877006307566
Organic Letters,An Efficient Asymmetric Synthesis of Manzacidin C,A brief synthesis of manzacidin C based on a chiral silane-promoted diastereo- and enatioselective acylhydrazone-alkene [3 + 2] cycloaddition reaction has been achieved. This synthesis is the first synthesis of any of the manzacidins wherein the C(4) and C(6) stereocenters are established in a single highly stereoselective step.,10.1021/ol8011869,2008-06-24,0.6332838194194461
Organic Letters,Total Synthesis of Epothilones B and D,[reaction: see text] A highly convergent total synthesis of the natural products epothilone B and D is described. The route is highlighted by efficient generation of a C12-C13 trisubstituted olefin which exploits a sequential Nozaki-Hiyama-Kishi coupling and a stereoselective thionyl chloride rearrangement.,10.1021/ol010094x,2001-06-12,0.6332808720934008
Organic Letters,A Strategy for the Total Synthesis of Dragmacidin E. Construction of the Core Ring System,[reaction: see text] The construction of the dragmacidin core ring system by a route that features the application of a new indole annelation reaction sequence is described.,10.1021/ol0617547,2006-09-15,0.6332721953855281
Tetrahedron,An alternate route in the synthesis of morphine,,10.1016/s0040-4039(01)89736-7,1967-01-01,0.6332599281704847
Tetrahedron,Semmler–Wolff aromatisation: a concise route for the synthesis of 5-amino-quinazolines and 4-amino-indoles,,10.1016/j.tetlet.2014.09.125,2014-10-03,0.6332364204980888
Synlett,"Facile Synthesis of 1,1,3-Tetramethylisoindole <i>N</i>-Oxide from 2-Chlorobenzoic Acid Using Reverse-Cope Cyclization as a Key Step","We have achieved an efficient alternative synthesis of 1,1,3-tetramethylisoindole N-oxide (1) using reverse-Cope cyclization as a key step, affording 1 in nine steps and 28% yield from 2-chlorobenzoic acid (2).",10.1055/s-2007-984900,2007-07-17,0.6332330659469734
Organic Process Research & Development,A Novel Synthesis of Rasagiline via a Chemoenzymatic Dynamic Kinetic Resolution,"A novel synthetic route for preparing rasagiline mesylate is presented using a dynamic kinetic resolution (DKR) as the key step, catalyzed by Candida antarctica lipase B (CALB) and a Pd nanocatalyst. The chiral intermediate ( R )-2,3-dihydro-1-indanamine was obtained through the DKR of the racemic aminoindan rac -1 in high yield (>90%) and excellent enantioselectivity (>99% ee). The process could be conducted on a 73 g scale at 200 g/L. Rasagiline mesylate was synthesized in 25% overall yield and excellent enantioselectivity (99.9% ee) over 7 steps.",10.1021/op500152g,2014-09-19,0.6332302716561036
Tetrahedron,"A general asymmetric route for the synthesis of the alexine and australine family of pyrrolizidine alkaloids. The first asymmetric synthesis of 1,2-diepi-alexine and 1,2,7-triepi-australine",,10.1016/j.tetlet.2005.10.074,2005-11-03,0.6332199204875559
Synthesis,"Synthesis of 7,8-Dimethoxy-2-oxo-1,3,4,5-tetrahydropyrrolo[4,3,2-de]quinoline: A Key Intermediate en Route to Makaluvamines, Discorhabdin C and Other Marine Alkaloids of this Group via Vicarious Nucleophilic Substitution of Hydrogen","All articles of this category The title compound 1a , a key intermediate in synthesis of an important group of alkaloids, is efficiently prepared via vicarious nucleophilic substitution of hydrogen followed by simple transformations. vicarious nucleophilic substitution - selective NO 2 hydrogenation - marine alkaloids precursor",10.1055/s-1997-1325,1997-10-01,0.6332144210698695
Organic Process Research & Development,"Development of a Scalable Synthesis of Mevidalen (LY3154207), an Orally Available Positive Allosteric Modulator of the Human Dopamine D1 Receptor","The evolution from early medicinal chemistry to large-scale production of the chemical synthesis of Lilly D1-positive allosteric modulator (PAM) mevidalen (LY3154207) and its hydroxybenzoate co-crystal is outlined. The issues and steps taken to resolve them are outlined across several generations of synthesis, including unexpected issues that arose during cryogenic addition of MeLi to a key imine intermediate and the use of flow chemistry to enable large-scale production. Ultimately, a process that was used to deliver >100 kg of API to support ongoing clinical trials is described.",10.1021/acs.oprd.0c00229,2020-09-22,0.6332136972810014
Synlett,Synthesis of the Core Structure of the Cyclocitrinols via SmI<sub>2</sub>-Mediated Fragmentation of a Cyclopropane Precursor,"The first synthetic entry towards the cyclocitrinols, a new class of natural products possessing a steroid-analogue structure with a characteristic bicyclo[4.4.1]undecane AB ring system, was elaborated. In the key step, a cyclopropanated intermediate (prepared from dehydroepiandrosterone) was subjected to reductive fragmentation (using SmI2 in THF).",10.1055/s-2007-984521,2007-07-01,0.6332024698494055
European Journal of Organic Chemistry,Stereoselective Total Synthesis of Pyranicin and 4‐<i>Epi</i>‐Pyranicin from Carbohydrate Precursors,"Abstract Herein, we describe a simple and efficient pathway for the total synthesis of pyranicin and 4‐ epi ‐pyranicin by utilizing carbohydrates as chiral raw materials for the first time. The general synthetic strategy involves the formation of two main fragments: Fragment 1 is the central tetrahydropyran core, which was constructed in a total of 10 steps from 2,3,4,6‐tetra‐ O ‐acetyl D‐glucal via Ferrier‐type rearrangement and oxidative cyclization as the key steps. Fragment 2 is the butenolide fragment, which was obtained in a gram scale with a total of 14 steps from diacetyl‐L‐rhamnal involving a ring contraction strategy.",10.1002/ejoc.202400244,2024-03-05,0.633199033273774
Organic Process Research & Development,"Scalable Process of Spiro(cyclopropane)oxazepane Pyridine Carboxylic Acid through Kulinkovich, Mitsunobu, and Pd-Catalyzed Intramolecular C–N Coupling","The oxazepane pyridine intermediate, an important fragment of active pharmaceutical ingredients, is of great interest in the pharmaceutical industry. In this manuscript, a scalable and economical process for the synthesis of a fused 2′,3′-dihydro-5’ H -spiro[cyclopropane-1,4′-pyrido[3,2-b][1,4]oxazepine]-8′-carboxylic acid 1 on multikilogram scales is described. The synthesis features a streamlined isolation process from the Mitsunobu reaction by using one solvent system for a two-step process. Furthermore, a robust palladium-catalyzed intramolecular amination for the seven-membered heterocycle was developed. The reproducible reaction rate was established by adding the catalyst and ligand as solids without preparing the palladium complex under nitrogen. The residual palladium was effectively reduced by recrystallization of the carboxylic ester intermediate 2 . The synthesis of key intermediate 5 was realized via the Kulinkovich reaction from readily available simple building blocks. The regulatory starting material compound 1 was isolated in a high-purity profile after saponification of the ester 2 with an overall yield of 70% over five steps.",10.1021/acs.oprd.2c00221,2022-09-01,0.6331781104454843
Journal of Organic Chemistry,"Ring Expansion of 4-Alkynylcyclobutenones. Synthesis of Piperidinoquinones, Highly Substituted Dihydrophenanthridines, Benzophenanthridines, and the Naturally Occurring Pyrrolophenanthridine, Assoanine","New synthetic routes to a variety of N-heterocyclic quinones and hydroquinones are described. These include thermolyses of 4-hydroxy-4-[4- N -(benzenesulfonyl)-4-aza-1,6-dialkynyl]cyclobutenones to piperidinoquinones and 4-hydroxy-4-[3-( N -phenylamino)-1-propynyl]cyclobutenones to dihydrophenanthridinediols. Included in the array of products available by this method are benzophenanthridines, indolophenanthridines, isoindoloindoles, and pyrrolophenanthridines. The methodology was employed in a five-step synthesis of the alkaloid assoanine starting with dimethyl squarate and indoline. The key step in all of these transformations is the ring expansion of appropriately substituted 4-hydroxy-4-alkynylcyclobutenones. These are envisaged to undergo electrocyclic ring opening to the corresponding enynylketenes which ring close to diradical intermediates that then lead to products via either radical additions to proximal alkyne moieties or undergo homolytic aromatic substitution to appropriately placed aryl groups. The synthetic scope and mechanism of the ring expansion reactions are discussed.",10.1021/jo9613803,1996-01-01,0.6331744785039144
Synthesis,Formal Synthesis of (R)-(+)-Lasiodiplodin,A catalytic approach is reported for the enantioselective synthesis of (R)-(+)- lasiodiplodin methyl ether using asymmetric hetero allylic alkylation as the key step.,10.1055/s-0030-1258453,2011-03-01,0.6331711745908694
Journal of Organic Chemistry,A Synthetic Approach to Several C7-Carbasugars via a Key Intramolecular Morita–Baylis–Hillman Reaction,"A new synthetic strategy for C7-carbasugars is developed via an intramolecular Morita–Baylis–Hillman reaction, in which a substituted dial precursor prepared from d -mannose cyclizes smoothly in the presence of DMAP to afford polyhydroxylated cyclohex-1-enecarbaldehyde with good yield. By employment of the cyclization products as key intermediates, the first syntheses of carbasugar ester 1 and epicorepoxydon A, as well as practical syntheses of epoxydines B and C, (−)-MK7607, (−)-streptol, and (−)-gabosine E are achieved.",10.1021/acs.joc.2c01992,2022-10-12,0.6331648941737011
Journal of Organic Chemistry,"An Enantioselective Synthetic Route to <i>cis</i>-2,4-Disubstituted and 2,4-Bridged Piperidines","A synthetic route to enantiopure cis-2,4-disubstituted and 2,4-bridged piperidines is reported, the key step being a stereoselective conjugate addition of an organocuprate to a phenylglycinol-derived unsaturated lactam bearing a substituent at the 8a-position.",10.1021/jo801172b,2008-07-31,0.6331563885926926
Tetrahedron,An expeditious convergent synthesis of a dibromotyrosine alkaloid inhibitor of mycothiol-S-conjugate amidase,,10.1016/j.tetlet.2005.07.109,2005-08-09,0.6331484049031608
Synlett,"Synthesis and cis-Dihydroxylation of 6H-1,2-Oxazines: Synthesis of Dihydroxyprolinols","All articles of this category An efficient synthesis of 6 H -1,2-oxazines 5a-f starting from α-halogen oximes 2a-f and β-bromo enol ether 1 is described. Compounds 5a-d were cis -dihydroxylated with KMnO 4 and compound 5e with the NaIO 4 /RuCl 3 reagent, respectively, to give the diastereomerically pure functionalized 1,2-oxazines 7a-e after protection. Intermediate 7a could be transformed into cis -dihydroxylated proline derivatives 8α, 8β which were converted to dihydroxyprolinols 10 α and 10 β or to the N-benzylated compounds 9α and 9β . This route constitutes a formal total synthesis of swainsonine 11 since 9β is a known intermediate in a published synthesis of this natural mannosidase inhibitor. 6 H -1,2-Oxazines - cis -Dihydroxylation - Pyrrolidine Derivatives - Hetero-Diels-Alder Reaction - Swainsonine",10.1055/s-1995-5161,1995-10-01,0.6331456588302845
Tetrahedron,Synthesis of tetradeuterated LTA4 methyl ester,,10.1016/0040-4039(88)85087-1,1988-01-01,0.6331450148257382
Tetrahedron,"Synthesis of 9α,11α-thiathromboxane A2 methyl ester",,10.1016/s0040-4039(00)88439-7,1982-01-01,0.6331450148257382
Tetrahedron,Synthesis of Δ7-prostaglandin A1 methyl ester,,10.1016/s0040-4039(00)02329-7,2001-02-01,0.6331450148257382
Organic Letters,Synthesis of Iriomoteolide-1a C13−C23 Fragment via Asymmetric Conjugate Addition and Julia−Kocienski Coupling Reaction,"The key C13-C23 fragment toward the total synthesis of iriomoteolide-1a (1) has been constructed from an 1,2-acetonide containing aldehyde 5 via a Julia-Kocienski olefination with the C16-C23 segment 6. The key step involves stereoselective introduction of the C29 methyl group by a highly efficient CuI-Tol-BINAP-catalyzed asymmetric conjugate addition of methylmagnesium bromide to an alpha,beta-unsaturated ester.",10.1021/ol901480s,2009-07-23,0.6331403851001306
Journal of Organic Chemistry,Total Synthesis of (−)-Carinatine A and (+)-Lycopladine A,"An efficient synthesis of two Lycopodium alkaloids, (-)-carinatine A and (+)-lycopladine A, is achieved in eight steps. The synthesis features an intramolecular aldol reaction for assembling the 6,5-fused ring system, a subsequent Tsuji-Trost allylation for generating a quarternary carbon center, and a 6π-electrocyclization to form the pyridine ring.",10.1021/acs.joc.6b01435,2016-08-03,0.633135288274971
Synlett,Formal Synthesis of Aspidospermidine via the Intramolecular Cascade Transannular Cyclization,"A formal synthesis of aspidospermidine is reported through a novel preparation of Stork’s penultimate tricyclic ketone intermediate. The key steps of the synthesis consist of an intramolecular cascade transannular cyclization, triggered by the removal of Boc group, which simultaneously forms the C, D, and E rings of aspidospermidine and conveniently setting up the quaternary stereo­center via decarboxylative alkylation reaction of the β-keto ester.",10.1055/s-0033-1338447,2013-05-08,0.6331335184437749
European Journal of Organic Chemistry,A Concise and Efficient Synthesis of Spiroketals – Application to the Synthesis of SPIKET‐P and a Spiroketal from <i>Bactrocera </i>Species,"Abstract We report the synthesis of spiroketals by sequence of enol ether synthesis and cyclization. The enol ethers were prepared from lactones by a Julia olefination reaction, and the starting chiral lactone was prepared from an industrial intermediate. This route is a concise and efficient way to synthesize naturally occurring and biologically interesting spiroketals. We used this sequence for the preparation of SPIKET‐P and a spiroketal from Bactrocera species.",10.1002/ejoc.201201199,2013-01-10,0.6331136716854711
Organic Letters,Expeditious Synthesis of <i>Mycobacterium tuberculosis</i> Sulfolipids SL-1 and Ac<sub>2</sub>SGL Analogues,"M. tuberculosis sulfoglycolipids SL-1 and Ac2SGL are highly immunogenic and potential vaccine candidates. A short and efficient methodology is reported for the synthesis of SL-1 and Ac2SGL analogues via regioselective functionalization of α,α-D-trehalose employing a highly regioselective late stage sulfation, as a key step. The SL-1 analogues 3a and 4 were obtained in 10 and 9 steps in 13.4% and 23.9% overall yields, respectively. The Ac2SGL analogue 5 was synthesized in 5 steps in 18.4% yield.",10.1021/ol5027987,2014-10-16,0.6331114881119773
European Journal of Organic Chemistry,Convenient Syntheses of Novel α- and β-Amino Acids with Spiropentyl Groups,"Racemic spiropentylglycine (8) has been synthesized by sodium borohydride reduction of benzyl (E/Z)-2-chloro-2-spiropentylideneacetate (5-Bn), nucleophilic substitution of the chlorine in the product 6 with azide and hydrogenolytic deprotection of the resulting 7 (overall yield 15%). An alternative approach to 8 consisted of the coupling of the higher-order cuprate 10, generated by halogen-metal exchange from bromospiropentane (9), with the electrophilic glycine equivalent 11 followed by deprotection (overall yield 47%). Enantiomerically pure (1′-aminospiropentyl)acetic acid [(R)-16] (overall yield 16% from 5-Me) and 1-aminospiropentanecarboxylic acid [(R)-23] (29% from 5-Me) were obtained from the Michael adduct 14-Me of (4R,5S)-4,5-diphenyloxazolidin-2-one (13) and methyl (E/Z)-2-chloro-2-spiropentylideneacetate (5-Me). Racemic 1-aminospiropentanecarboxylic acid (R/S-23) was prepared by rhodium-catalyzed addition of dimethyl diazomalonate to methylenecyclopropane and subsequent Curtius degradation of the halfester 28 via the azide 29 (overall yield 14%). Upon standing in aqueous solution, 23 underwent complete rearrangement to the new 1-amino-2-methylenecyclobutanecarboxylic acid (24). The interesting derivative of azabicyclo[3.1.0]hexane-1-carboxylate 34 with an annelated spiropentane moiety and a β-amino acid fragment was incidentally obtained in a one-step intermolecular domino reaction starting with the addition of lithium benzylamide to methyl 2-chloro-2-cyclopropylideneacetate (32, 41% yield).",10.1002/(sici)1099-0690(199911)1999:11<3105::aid-ejoc3105>3.0.co;2-1,1999-11-01,0.633106549340791
Journal of Organic Chemistry,Scalable Synthesis of the VEGF-R2 Kinase Inhibitor JNJ-17029259 Using Ultrasound-Mediated Addition of MeLi−CeCl<sub>3</sub> to a Nitrile,"The preparation of the selective VEGF-R2 kinase inhibitor 10 (JNJ-17029259) is described in which the key precursor, 4-(5-isoxazolyl)benzonitrile, undergoes clean transformation to the corresponding cumylamine derivative with CeCl(3)-MeLi in THF. This high-yielding cerium mediated transformation is robust, reproducible, and readily scalable based on a requirement for the anhydrous CeCl(3) to be milled and subjected to ultrasound treatment prior to addition of methyllithium.",10.1021/jo7021372,2008-01-03,0.6330840736356378
Organic Letters,Formal Syntheses of (−)-Quinocarcinamide and (−)-Quinocarcin,"Concise and scalable formal syntheses of (−)-quinocarcinamide and (−)-quinocarcin have been achieved in 9 steps with 9% overall yield from simple commercially available chemicals. The synthetic strategy features an ortho -regioselective Pictet–Spengler cyclization for the construction of the tetrahydroisoquinoline skeleton, a stereoselective formal intramolecular [3 + 2] cross cycloaddition of cyclopropane 1,1-diester with an imine for the construction of the 3,8-diazabicyclo[3.2.1]octane skeleton.",10.1021/acs.orglett.4c02267,2024-08-15,0.6330770878903934
Angewandte Chemie International Edition,Total Synthesis of (±)‐Phomoidride D,Abstract Described herein is a synthetic strategy for the total synthesis of (±)‐phomoidride D. This highly efficient and stereoselective approach provides rapid assembly of the carbocyclic core by way of a tandem phenolic oxidation/intramolecular Diels–Alder cycloaddition. A subsequent SmI 2 ‐mediated cyclization cascade delivers an isotwistane intermediate poised for a Wharton fragmentation that unveils the requisite bicyclo[4.3.1]decene skeleton and sets the stage for synthesis completion.,10.1002/anie.201712369,2017-12-29,0.6330769112113943
Tetrahedron,"Convenient one-pot synthesis of functionalized unsymmetrical (Z) or (E)-enediynes from (Z) or (E)-1,2-dichloroethylene. An efficient route to (Z,Z,Z) and (Z,E,Z)-trienes",,10.1016/s0040-4039(00)73232-1,1994-05-01,0.6330709719387209
Tetrahedron,Antitumor ether lipids: An improved synthesis of ilmofosine and an enantioselective synthesis of an ilmofosine analog,,10.1016/s0040-4039(00)77004-3,1994-04-01,0.6330568111432476
Tetrahedron,"A new synthesis of monosubstituted succinaldehydes and 3-substituted pyrroles from acetonitriles. Formal synthesis of 2,3-dihydro-7-methyl-2H-pyrrolizidin-1-one (Danaidone), a semiochemical of danaid butterflies",,10.1016/0040-4039(96)00765-4,1996-06-01,0.6330551658304868
Synlett,A Short High Yielding Route to Methyl 2-(Quinuclidin-2-yl)acetate,"All articles of this category The intramolecular Michael reaction of 3 , which can be prepared in high yield from alcohol 4 , provides the basis for a short efficient route to methyl 2-(quinuclidin-2-yl)acetate 1 .",10.1055/s-1993-22598,1993-01-01,0.6330533387707444
Tetrahedron,The photolysis of adducts derived from o-chloranil a new route to dihydrobarrelenes,,10.1016/s0040-4039(01)84271-4,1972-01-01,0.6330428152150681
Organic Letters,Second-Generation Total Synthesis of Haterumalide NA Using <i>B</i>-Alkyl Suzuki–Miyaura Coupling,"Second-generation total synthesis of haterumalide NA, a potent cytotoxic marine macrolide, was achieved by using B-alkyl Suzuki-Miyaura coupling and Nozaki-Hiyama-Kishi coupling as key steps (1.2% in 33 steps). Compared to our first-generation approach, the second-generation synthesis is much improved in the yield of key intermediate.",10.1021/ol800554f,2008-04-09,0.6330409938821981
European Journal of Organic Chemistry,Studies on the Total Synthesis of Hirtellanine A: Regioselective Synthesis of Benzopyran,"Abstract The total synthesis of Hirtellanine A was accomplished by two different synthetic approaches. Hirtellanine A was assembled using a one‐pot, tandem acid‐mediated deprotection and tautomerization cascade starting from quinone derivative 23 . The key features of the synthesis include a Houben–Hoesch reaction of aryl cyanide 3 with phloroglucinol, a one‐pot sequential boronation, a Suzuki–Miyaura cross‐coupling of aryl bromide 33 with aryl iodide 26 , and a base‐mediated regioselective Claisen rearrangement for the benzopyran construction.",10.1002/ejoc.201201339,2013-01-24,0.6330335687358706
European Journal of Organic Chemistry,Total Synthesis of Tabernanthine and Ibogaline: Rapid Access to Nosyl Tryptamines,"We describe the first total syntheses of tabernanthine and ibogaline. Entry to these iboga alkaloid natural products is enabled by a thermal coupling of indoles and aziridines to furnish the requisite nosyl tryptamine starting materials. This route features a Friedel-Crafts type alkylation to form the key indole-isoquinuclidine C-C bond. Finally, a regio- and diastereoselective hydroboration-oxidation enables C-N bond formation to close the isoquinuclidine ring system and deliver tabernanthine and ibogaline in 10 and 14% yield respectively. Both syntheses were completed in eight steps.",10.1002/ejoc.202400442,2024-04-26,0.6330255532853571
Journal of Organic Chemistry,Total Synthesis of Streptonigrone,"A total synthesis of streptonigrone, 1, is described, which incorporates a one-step synthesis of substituted pyridones devised in our laboratory. Other aspects of the synthesis that differentiate the present approach from previous ones are the use of a Conrad-Limpach reaction, rather than the customary Friedländer methodology, to assemble the quinoline segment of 1, and the implementation of an anionic sequence for the functionalization of a key pyridone intermediate.",10.1021/jo701435p,2007-10-01,0.6330102773456061
Synthesis,A Novel and Efficient Synthesisof Dihydrexidine,An efficient synthesis of the dopamine D1 selective full agonist dihydrexidine has been achieved in high yields and requiring no chromatographic separations via a facilitated intramolecular Henry cyclization of a (nitropropyl)benzophenone and subsequent diastereomerically selective reduction of the resulting tricyclic nitroalkene.,10.1055/s-0028-1083359,2009-02-11,0.6330060765808273
Synlett,First Total Synthesis of the Marine-Derived Anti-inflammatory Natural Product (–)-Herdmanine D through a Steglich Esterification,"Abstract An efficient and regioselective route for the first total synthesis of the antiinflammatory marine natural product (–)-herdmanine D, with an excellent overall yield of 18%, is described. A key feature of the synthetic strategy is a Steglich esterification of regioselectively constructed 6-bromo-5-methoxy-1H-indole-3-carboxylic acid with protected l-tyrosine. The formation of the l-isomer was confirmed through measurement of the optical activity. The current strategy paves the way for the construction of diverse analogues of (–)-herdmanine D for drug development.",10.1055/a-1672-3000,2021-10-19,0.6329553019964143
Angewandte Chemie International Edition,Enantioselective Total Synthesis of Cylindramide,"Key steps in the convergent enantioselective synthesis of the cytotoxic natural product (see structural formula) are tandem Michael addition/electrophilic trapping reactions, Sonogashira coupling, Julia–Kocienski olefination, and macrocyclization. Formation of the tetramic acid completed the synthesis.",10.1002/anie.200461823,2004-12-31,0.6329509431964977
Synlett,"Study on Disulfur-Backboned Nucleic Acid: Part 1, Efficient Synthesis of 3′,5′-Dithio-2′-Deoxyadenosine","An efficient procedure is established to synthesize 3′,5′-dithio-2′-deoxyadenosine starting from 2′-deoxyadenosine in five steps in 33% overall yield. In this procedure, the key intermediate 9 was synthesized by twice SN2 reactions with twice 3′-configuration inversions and then it was deprotected to title compound by removing three acyl groups in one pot.",10.1055/s-2004-834809,2004-10-20,0.6329502956612983
Journal of the American Chemical Society,Enantioselective Total Synthesis of (−)-Alstoscholarisine A,"We report a concise and highly enantioselective total synthesis of (-)-alstoscholarisine A (1), a recently isolated monoterpenoid indole alkaloid that has significant bioactivity in promoting adult neuronal stem cells proliferation. A highly enantioselective (99% ee), intramolecular Ir-catalyzed Friedel-Crafts alkylation of indole 9 with a secondary allylic alcohol was utilized to establish the first stereogenic center upon which the other three contiguous chiral centers were readily set by a highly stereoselective tandem 1,4-addition and aldol reaction. The key tetrahydropyran was constructed through a hemiacetal reduction, and the final aminal bridge was forged by a one-pot reductive amination/cyclization. The conciseness of this approach was highlighted by building core bonds in each step with a minimalist protecting group strategy.",10.1021/jacs.6b00625,2016-02-16,0.6329367110534612
Journal of Organic Chemistry,"A Novel Asymmetric Route to the 1,3-Disubstituted Tetrahydroisoquinoline, (−)-Argemonine","Chiral bicyclic lactam 13 was converted to the natural product (-)-argemonine 9 in six steps. This novel route to argemonine represents a general strategy for the preparation of chiral 1,3-disubstituted tetrahydroisoquinolines.",10.1021/jo960110h,1996-01-01,0.6329367069985673
Synthesis,Asymmetric Syntheses of All Stereoisomers of 3-Hydroxyproline; A Constituent of Several Bioactive Compounds,"Synthesis of an unusual β-hydroxy-α-amino acid, 3-hydroxyproline, and its derivatives have been achieved enantioselectively by employing Sharpless asymmetric epoxidation and reductive cyclization as the key steps.",10.1055/s-0032-1316734,2012-08-16,0.6329145087358181
Chemical Science,Fusarisetin A: scalable total synthesis and related studies,"Fusarisetin A (1) is a recently isolated natural product that displays an unprecedented chemical motif and remarkable bioactivities as a potent cancer migration inhibitor. We describe here our studies leading to an efficient and scalable total synthesis of 1. Essential to the strategy was the development of a new route for the formation of a trans-decalin moiety of this compound and the application of an oxidative radical cyclization (ORC) reaction that produces fusarisetin A (1) from equisetin (2) via a bio-inspired process. TEMPO-induced and metal/O(2)-promoted ORC reactions were evaluated. Biological screening in vitro confirms the reported potency of (+)-1. Importantly, ex vivo studies show that this compound is able to inhibit different types of cell migration. Moreover, the C(5) epimer of (+)-1 was also identified as a potent cancer migration inhibitor, while (-)-1 and 2 were found to be significantly less potent. The optimized synthesis is applicable on gram scale and provides a solid platform for analogue synthesis and methodical biological study.",10.1039/c2sc21308g,2012-01-01,0.632885372234058
Tetrahedron,Steroids CCCXII. A new synthetic route to bisdehydrodoisynolic acids.,,10.1016/s0040-4039(01)89901-9,1967-01-01,0.6328746857577175
Organic Process Research & Development,"Highly Selective Synthesis of 2-(2<i>H</i>-1,2,3-Triazol-2-yl)benzoic Acids","A selective and scalable synthesis of 2-(2 H -1,2,3-triazol-2-yl)benzoic acid starting from 1-fluoro-2-nitrobenzene derivatives is presented. The four-step synthesis introduces the triazole at the start via N 2 -arylation of 4,5-dibromo-2 H -1,2,3-triazole. A sequence of consecutive functional group transformations, namely hydrogenation, Sandmeyer iodination, and Grignard carboxylation, provides the target molecules in a reliable and scalable manner. The usefulness of this method is demonstrated by the synthesis of di- or tri(2 H -1,2,3-triazol-2-yl)benzene derivatives, which are difficult to produce by other methods.",10.1021/acs.oprd.8b00349,2019-01-18,0.6328675969973622
Journal of Organic Chemistry,Enantiomerically Pure Synthesis of β-Substituted γ-Butyrolactones:  A Key Intermediate to Concise Synthesis of Pregabalin,"Chiral beta-substituted gamma-butyrolactones are known to be important intermediates for many biologically active compounds such as gamma-aminobutyric acid (GABA) derivatives and lignans. We have developed a general, convenient, and scalable synthetic method for enantiomerically pure beta-substituted gamma-butyrolactones, with either configuration, via nucleophilic cyclopropane ring opening of (1S,5R)- or (1R,5S)-bicyclic lactone followed by decarbethoxylation. The utility of our method was demonstrated by streamlined synthesis of pregabalin ((S)-3-isobutyl-gamma-aminobutyric acid), an anticonvulsant drug for the treatment of peripheral neuropathic pain.",10.1021/jo0709605,2007-08-23,0.6328609724627444
European Journal of Organic Chemistry,"Gram Scale Total Synthesis of 2‐Hydroxy‐3‐methylcarbazole, Pyrano[3,2‐<i>a</i>]carbazole and Prenylcarbazole Alkaloids","Abstract Naturally occurring carbazole alkaloids including 2‐hydroxy‐3‐methylcarbazole, pyrano[3,2‐ a ]carbazole alkaloids (girinimbine and murrayacine) and prenylcarbazole alkaloids (mukoenine‐A and heptaphylline) have been synthesized on gram scale. The key compound in these syntheses is 9‐benzyl‐2‐methoxy‐3‐methylcarbazole, which was prepared by an efficient Au‐catalyzed cyclization reaction of readily available methoxypropadiene and indole‐2‐carbaldehyde. Girinimbine and murrayacine were synthesized by a concise PhB(OH) 2 ‐mediated intermolecular cyclization with 3‐methylbut‐2‐enal. Palladium‐catalyzed allylation/Claisen rearrangement proved to be the best route to mukoenine‐A and heptaphylline.",10.1002/ejoc.201500783,2015-07-27,0.6328581490350633
Organic Letters,Total Synthesis of (+)-Discodermolide:  An Improved Endgame Exploiting a Still−Gennari-Type Olefination with a C1−C8 β-Ketophosphonate Fragment,"[structure: see text] An improved, third-generation, total synthesis of (+)-discodermolide, a potent microtubule-stabilizing anticancer agent of marine sponge origin, is achieved in 11.1% yield over 21 steps. Key steps include a Still-Gennari HWE olefination, performed using NaH as the base, between C1-C8 beta-ketophosphonate 7 and C9-C24 aldehyde 8, introducing the (8Z)-alkene with 10:1 selectivity, and K-Selectride reduction of the derived enone 16, installing the (7S)-configuration.",10.1021/ol0478842,2004-11-23,0.6328407678550317
Tetrahedron,"Stereocontrolled synthesis of spirocyclopropane sugars and their application to asymmetric formation of tertiary chiral centres: A route to 2,2′-dialkylated pyranose subunit (C18C23) of lasonolide A",,10.1016/0040-4039(96)01991-0,1996-11-01,0.6328318042996359
Journal of Organic Chemistry,Formal Synthesis of Angiogenesis Inhibitor NM-3,"We report the formal synthesis of angiogenesis inhibitor NM-3 (1) in six steps from either of the 2,4-dimethoxyhalobenzenes 13a,b or 3,5-dimethoxychlorobenzene (13c). The first key reaction is the regiospecific alkylation/rearrangement between the aryne derived from 13a-c with sodium diethylmalonate in THF to produce diester 11, which after hydrolysis and cyclization affords homophthalic anhydride 3. The second is the reaction of anhydride 3 with either ethyl 2-methylmalonate (28a), in the presence of 1,1'-carbonyldiimidazole, or ethyl-2-methylmalonyl chloride (28b) under basic conditions to afford key isocoumarin 27. The conversion of 27 constitutes a formal synthesis of NM-3.",10.1021/jo034165c,2003-06-20,0.6328257675278938
Journal of Organic Chemistry,Total Synthesis of (−)-Cleistenolide,"The first total synthesis of Cleistenolide, a novel natural product recently isolated from the Annonaceae species Cleistochlamys kirkii Oliver, is described. The synthesis proceeds in six steps and 18% overall yield, starting from an enantiopure C2-symmetric building block and using a Sharpless epoxidation, a selective epoxide opening, and a ring-closing metathesis reaction.",10.1021/jo1002642,2010-03-11,0.6328223391737287
Synlett,"A Flexible, Efficient Synthesis of (±)-Carbocyclic Phosphonic Acid Nucleoside Derivatives",An efficient and flexible synthesis of cyclopentane and hydroxylated cyclopentane phosphonic acid analogues is described. The key step involves the opening of an epoxide with either a nu­cleoside base or a selenyl anion to access the target molecules.,10.1055/s-2005-863745,2005-01-01,0.6328028944234584
Organic Letters,"Stereocontrolled Synthesis of 2,4-Diamino-3-hydroxyacids Starting from Diketopiperazines:  A New Route for the Preparation of Statine Analogues","Chiral 3-aminopyrrolidine-2,4-diones, obtained by transannular rearrangement of activated diketopiperazines, could be a springboard toward an exceptional stereoselective synthesis of original 2-disubstituted statines. After a selective reduction of the pyrrolidine-2,4-diones, the access to opened 2,4-diamino-3-hydroxyacid esters was carried out by a subsequent alkaline treatment or directly through a tandem reduction-solvolysis.",10.1021/ol7021593,2007-10-16,0.6327957632885294
European Journal of Organic Chemistry,Stereoselective Synthesis of the C31–C41 Spirolactam Fragment of Sanglifehrin A,"Abstract A stereoselective synthesis of the spirolactam fragment (C31–C41) of a highly‐potent immunosuppressant sanglifehrin A is described. The key steps involved in this synthesis are a desymmetrization protocol, Sharpless asymmetric epoxidation, Crimmins syn aldol reaction, Barton–McCombie deoxygenation, and acid‐mediated spirolactamization.",10.1002/ejoc.201201684,2013-04-15,0.6327764965324538
Journal of Organic Chemistry,Synthesis of Reboxetine Intermediate and Carnitine Acetyltransferase Inhibitor via NBS-Induced Electrophilic Multicomponent Reaction,"N-Bromosuccinimide-induced electrophilic multicomponent reaction has been applied to the synthesis of Reboxetine intermediate, a highly potent selective norepinephrine reuptake inhibitor. By simply changing the olefinic partner, the synthesis of a carnitine acetyltransferase inhibitor, which contains a 2,6,6-trisubstituted morpholine system, can be accomplished.",10.1021/jo500609a,2014-04-17,0.632774870556639
Tetrahedron,A novel stereoselective route to γ-butyrolactones,,10.1016/s0040-4039(00)91589-2,1992-02-01,0.6327644772467707
Organic Letters,"Stereoselective Synthesis of Tetrahydrofuran Lignans via BF<sub>3</sub>·OEt<sub>2</sub>-Promoted Reductive Deoxygenation/Epimerization of Cyclic Hemiketal:  Synthesis of (−)-Odoratisol C, (−)-Futokadsurin A, (−)-Veraguensin, (+)-Fragransin A<sub>2</sub>, (+)-Galbelgin, and (+)-Talaumidin","A versatile route to the synthesis of 2,5-diaryl-3,4-dimethyltetrahydrofuran lignans, (-)-odoratisol C (1), (-)-futokadsurin A (2), (-)-veraguensin (3), (+)-fragransin A2 (4), (+)-galbelgin (5), and (+)-talaumidin (6), is described. Central to the synthesis of the lignans is BF(3) x OEt(2)-promoted deoxygenation/epimerization of the hemiketal 9a followed by stereoselective reduction of the oxocarbenium ion intermediates 8a,b.",10.1021/ol7016388,2007-09-01,0.6327565507697512
Journal of the American Chemical Society,Total Synthesis of Truncated Brevetoxin B [AFGHIJK],"Brevetoxin B ( l) ,1 a member of the ""red tide""-associated class of marine neurotoxins2 possesses a striking biological profile as a sodium channel modulator3 and a formidable molecular structure that includes 11 fused rings and 23 stereocenters.Several synthetic methods and schemes have been advanced toward the synthesis of this molecule,4 5 but to date, no total synthesis of brevetoxin B (1) or designed analogs have been reported.Herein we report the design and synthesis of a novel version of this compound, truncated brevetoxin B [AFGHIJK] (2), in which all the functionality within the natural compound is present, except for the internal rings BCDE (Figure 1).Such a design was considered important in that it could test the ""length hypothesis* of the brevetoxins3*b and provide useful information about their receptor.30n attractive bond disconnection across the oxocene ring of 2 revealed two domains (3 and 4) that could be coupled in the synthetic direction via a Wittig reaction and cyclized to produce the desired polycyclic framework.This convergent synthesis began with the construction of intermediates 3 (Scheme 1) and 4 (Scheme 2).Swern oxidation of the alcohol 56 (Scheme 1) followed by addition of MeMgBr and subsequent reoxidation gave rise to ketone 6 in 94% overall yield.After desilylation, the liberated alcohol 7 was converted to the bromoacetate ester 8, which upon exposure to (MeO)3P at 180 C afforded the phosphonate 9 in 74% overall yield from 6.A modified Homer-Emmons7 reaction was then used for the ring closure of 9 to 10 (88%).Reduction of 10 to the corresponding dihydropyran 12 was achieved by sequential treatment with DIBALH and BFyEtjO/EtaSiH the intermediacy of lactol (1)",10.1021/ja00099a081,1994-10-01,0.632755070245185
Journal of Organic Chemistry,"Studies on the Synthesis of Phlegmarine-Type <i>Lycopodium</i> Alkaloids: Enantioselective Synthesis of (−)-Cermizine B, (+)-Serratezomine E, and (+)-Luciduline","The synthesis of the Lycopodium alkaloids, (-)-cermizine B, (+)-serratezomine E, and (+)-luciduline using phenylglycinol-derived tricyclic lactams as chiral scaffolds, is reported. The requisite lactams are prepared by a cyclocondensation reaction between ( R)- or ( S)-phenylglycinol and the substituted δ-keto ester 11, easily accessible from ( R)-pulegone. The factors governing the stereoselectivity of these cyclocondensation reactions are discussed. Key steps of the synthesis from the stereochemical standpoint are the stereoselective elaboration of the allyl substituent to the ( S)-2-(piperidyl)methyl moiety and the stereoselective removal of the chiral inductor to give a cis-decahydroquinoline.",10.1021/acs.joc.8b00983,2018-06-27,0.6327502314663538
Tetrahedron,Synthesis of macrocyclic terpenoids by intramolecular cyclization VII. Total synthesis of (±)-cubitene,,10.1016/s0040-4039(00)87625-x,1982-01-01,0.632746708160825
Tetrahedron,Synthesis and resolution of a new helically chiral azahelicene,,10.1016/j.tetlet.2008.04.135,2008-04-28,0.6327250920889581
Organic Process Research & Development,Process Development of an N-Benzylated Chloropurine at the Kilogram Scale,"A two-step pharmaceutical manufacturing process was developed for the large-scale preparation of 6-chloro-9-((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)-9 H -purin-2-amine methanesulfonic acid salt ( 4 ) from commercially available starting materials. In the first step, the benzylpurine free base ( 3 ) was prepared by benzylation of 6-chloro-9 H -purin-2-amine ( 1 ) with 2-(chloromethyl)-4-methoxy-3,5-dimethylpyridine hydrochloride ( 2 ). The benzylpurine free base was then directly converted into the methanesulfonic acid salt. It was necessary to charge the pyridine hydrochloride 2 in portions into the mixture of K 2 CO 3 (−325 mesh) and the chloropurine compound 1 in dimethylacetamide (DMA). The major regioisomeric impurity ( 6 ), formed by N 7 benzylation, and inorganic salts were removed by filtration. Treatment of the DMA filtrate with MsOH afforded the target salt with negligible degradation. In the second step, recrystallization of the crude salt from DMSO–EtOAc with seeding gave crystalline API in high yield and purity despite the hydrolytic instability of the product in solution.",10.1021/op5003903,2015-02-23,0.6327102925109602
Journal of the American Chemical Society,Total Synthesis of<i>N</i>-Methylwelwitindolinone D Isonitrile,"Described is a concise total synthesis of N-methylwelwitindolinone D isonitrile, the first in a family of complex bicyclo[4.3.1]decane-containing indole alkaloids to yield to synthesis. The complete carbon core of the natural product was assembled rapidly through a Lewis acid-mediated alkylative coupling followed directly by a palladium-catalyzed enolate arylation reaction. The final ring of the pentacycle was introduced by an indole oxidation/cyclization, and the isonitrile was installed through the rearrangement of an aldehyde to an isothiocyanate followed by desulfurization.",10.1021/ja201834u,2011-03-29,0.6327046206422101
Chemical Science,Palladium-catalyzed nucleomethylation of alkynes for synthesis of methylated heteroaromatic compounds,"Herein, we disclosed a novel and efficient palladium-catalyzed nucleomethylation of alkynes for the simultaneous construction of the heteroaromatic ring and methyl group. The 3-methylindoles, 3-methylbenzofurans and 4-methylisoquinolines were obtained in moderate to excellent yields. Notably, this methodology was employed as a key step for synthesis of a pregnane X receptor antagonist, zindoxifene, bazedoxifene and AFN-1252. The kinetic studies revealed that reductive elimination might be the rate-determining step.",10.1039/d2sc03294e,2022-01-01,0.6326996030276492
Synthesis,"Molten-State Nitration of Substituted Imidazoles: New Synthetic Approaches to the Novel Melt-Cast Energetic Material, 1-Methyl-2,4,5-trinitroimidazole","Novel, one-step synthetic routes for the preparation of 1-methyl-2,4,5-trinitroimidazole (MTNI) are described. In addition, a new, molten-state nitration method for the synthesis of 1-methyl-2,4,5-trinitroimidazole is developed.",10.1055/s-0030-1260148,2011-08-02,0.6326953282410028
Organic Letters,"Enantiospecific Total Synthesis of (−)-Bakkenolide III and Formal Total Synthesis of (−)-Bakkenolides B, C, H, L, V, and X","A concise enantiospecific synthesis of (-)-bakkenolide III was accomplished from (S)-(+)-carvone. The key step involved radical cyclization of an iodoketone intermediate which afforded the cis-hydrindanone skeleton. Further synthetic transformations generated bakkenolide III, which also constitutes the formal total synthesis of (-)-bakkenolides, B, C, H, L, V, and X.",10.1021/ol071124k,2007-07-24,0.6326872033500166
Synthesis,Efficient Preparation of (3<i>S</i>)-3-(4-Fluorobenzyl)piperidinium Mandelate,"Methods for the preparation of (3S)-3-(4-fluorobenzyl)piperidine (2) and its mandelate salt (9) are described. The first generation synthesis started from 3-benzylpiperidone, and required Boc protection of the nitrogen for efficient separation of the enan­tiomers using chromatography on a chiral stationary phase. Subsequently, a resolution method using (R)-mandelic acid, produced high %ee salt 9 after recrystallization and eliminated the need for Boc protection. The third generation route, starting from pyridine-3-carboxaldehyde, led to a streamlined synthesis of racemate 2 and was optimized for producing multi-hundred gram quantities of the chiral salt.",10.1055/s-2004-834903,2004-11-02,0.632675689246639
Journal of Organic Chemistry,An Enantioselective Synthesis of (<i>S</i>)-(+)-3-Aminomethyl-5-methylhexanoic Acid via Asymmetric Hydrogenation,"A concise enantioselective synthesis of (S)-(+)-3-aminomethyl-5-methylhexanoic acid (1, Pregabalin) has been developed. The key step is the asymmetric hydrogenation of a 3-cyano-5-methylhex-3-enoic acid salt 2 with a rhodium Me-DuPHOS catalyst, providing the desired (S)-3-cyano-5-methylhexanoate 3 in very high ee. Subsequent hydrogenation of the nitrile 3 with a heterogeneous nickel catalyst provides Pregabalin 1 in excellent overall yield and purity.",10.1021/jo034397b,2003-06-06,0.6326744176989623
Organic Process Research & Development,"Facile One-Pot Process for Large-Scale Production of Highly Pure Bosentan Monohydrate, an Endothelin Receptor Antagonist","Described is an efficient, economic, and one-pot process for the production of highly pure bosentan ( 1 ), an endothelin receptor antagonist. The synthesis comprises the reaction of 4,6-dichloro-5-(2-methoxyphenoxy)-2,2′-bipyrimidine ( 2 ) with 4- tert -butylbenzenesulfonamide ( 3 ) and ethylene glycol ( 4 ) in acetonitrile in the presence of potassium carbonate to yield bosentan ( 1 ) in the same pot. The present work also describes a novel purification method for the removal of critical dimer impurity ( 7 ) and 6-hydroxy impurity ( 8 ) in 1 by preparation of bosentan ammonium salt ( 6 ) using inexpensive ammonium hydroxide. Upon purification, bosentan monohydrate ( 1 ) with an overall yield of 68% and HPLC purity of 99.90% was achieved.",10.1021/op200197z,2011-09-14,0.6326728142649768
Tetrahedron,"Prelaureatin, a new biogenetic key intermediate isolated from Laurencia nipponica",,10.1016/0040-4039(91)80093-l,1991-09-01,0.6326703803898643
Synthesis,Second-Generation Synthesis of (-)-Viriditoxin,"Viriditoxin is a secondary metabolite isolated from Aspergillus viridinutans that has been shown to inhibit FtsZ, the bacterial homologue of eukaryotic tubulin. A streamlined, scalable, and highly diastereoselective synthesis of this complex natural product is described. Key advances include a more efficient synthesis of the requisite unsaturated pyranone, scalable assembly of the naphthopyranone monomer, and improved diastereoselectivity in the biaryl-coupling reaction. In addition, we disclose a serendipitous ruthenium-catalyzed anion dimerization resulting from trace metal left by an RCM reaction.",10.1055/s-0031-1289651,2012-01-16,0.6326701876351943
Journal of the American Chemical Society,Total Synthesis of (+)-Allocyathin B<sub>2</sub>,"The first enantioselective synthesis of (+)-allocyathin was achieved. The synthesis features a Pd-catalyzed asymmetric allylic alkylation to install the first quaternary center, a Ru-catalyzed diastereoselective cycloisomerization to construct the six-membered ring, and a diastereoselective hydroxylative Knoevenagel reaction to introduce the final hydroxyl group. The unusual olefin isomerization of the Ru-catalyzed cycloisomerization was discussed and exploited for the synthesis.",10.1021/ja0435586,2005-02-11,0.6326690008665683
European Journal of Organic Chemistry,First Enantioselective Synthesis of Marine Diterpene Ambliol‐A,"Abstract The first enantioselective synthesis of furanditerpene ambliol‐A, which is a major metabolite of marine sponge Dysidea amblia , has been accomplished by starting from racemic α‐ionone. The key steps of the synthesis include lipase‐mediated resolution of 4‐hydroxy‐γ‐ionone, its stereoselective transformation into trans ‐α‐epoxy‐dihydroionone, C 2 homologation to trans ‐α‐epoxy‐monocyclofarnesyl acetate and Li 2 CuCl 4 ‐catalysed sp 3 –sp 3 cross‐coupling reaction of the latter ester with (furan‐3‐ylmethyl)magnesium chloride. This work confirms the chemical structure previously assigned to ambliol‐A and proves that the natural levorotatory isomer does not possess (1 S ,2 S ) absolute configuration, as previously indicated, but is the opposite enantiomer, (1 R ,2 R )‐2‐[( E )‐6‐(furan‐3‐yl)‐3‐methylhex‐3‐enyl]‐1,3,3‐trimethylcyclohexanol.",10.1002/ejoc.201403610,2015-02-17,0.6326646788851479
Journal of Organic Chemistry,Stereocontrolled Synthesis of a Potential Transition-State Inhibitor of the Salicylate Synthase MbtI from <i>Mycobacterium tuberculosis</i>,"Mycobactins are small-molecule iron chelators (siderophores) produced by Mycobacterium tuberculosis (Mtb) for iron mobilization. The bifunctional salicylate synthase MbtI catalyzes the first step of mycobactin biosynthesis through the conversion of the primary metabolite chorismate into salicylic acid via isochorismate. We report the design, synthesis, and biochemical evaluation of an inhibitor based on the putative transition state (TS) for the isochorismatase partial reaction of MbtI. The inhibitor mimics the hypothesized charge buildup at C-4 of chorismate in the TS as well as C-O bond formation at C-6. Another important design element of the inhibitor is replacement of the labile pyruvate side chain in chorismate with a stable C-linked propionate isostere. We developed a stereocontrolled synthesis of the highly functionalized cyclohexene inhibitor that features an asymmetric aldol reaction using a titanium enolate, diastereoselective Grignard addition to a tert-butanesulfinyl aldimine, and ring closing olefin metathesis as key steps.",10.1021/acs.joc.5b00455,2015-06-02,0.6326458367087553
Journal of Organic Chemistry,"Direct Synthesis of 1,1‘-[1,4-Phenylenebis(methylene)]-bis- 1,4,8,11-tetraazacyclotetradecane Octahydrochloride (AMD 3100) without the Use of Protecting Groups","A four-step synthesis of the title compound starting from methyl acrylate, ethylenediamine, and dimethyl malonate is reported. The synthesis can be run on a multigram scale and is operationally simple. The use of protecting groups is avoided by utilizing the trioxocyclam as the key coupling intermediate.",10.1021/jo030146r,2003-07-17,0.6326311963553976
Journal of the American Chemical Society,Asymmetric Total Synthesis of Cyclocitrinol,"The first and asymmetric total synthesis of cyclocitrinol, an unusual C25 steroid, has been accomplished in a linear sequence of 18 steps from commercially available compound 11. The synthetically challenging bicyclo[4.4.1] A/B ring system with a strained bridgehead (anti-Bredt) double bond of cyclocitrinol was constructed efficiently and diastereoselectively via a type II intramolecular [5 + 2] cycloaddition.",10.1021/jacs.8b02629,2018-04-04,0.6326300983136363
Organic Letters,Total Synthesis of Hoiamide C,"Hoiamide C was synthesized in 16 steps with an overall yield of 1.8% starting from homoallylic alcohol 18, unambiguously confirming its structure.",10.1021/ol2007567,2011-04-07,0.6325903071308484
Journal of Organic Chemistry,Chemo- and Diastereoselective Hydrosilylation of Amorphadiene toward the Synthesis of Artemisinin,"A formal synthesis of artemisinin starting from amorphadiene is described. This new route relies on the development of a catalytic chemo- and diastereoselective hydrosilylation. The practicability of this method is demonstrated by converting amorphadiene to dihydroartemisinic aldehyde using a one-pot hydrosilylation/oxidation sequence, minimizing the number of purifications and maximizing the productivity through a practical one-pot procedure. In addition, this approach can be coupled with a crystallization-induced diastereoselective transformation (CIDT) to enhance the optical purity of the key target intermediate, dihydroartemisinic aldehyde.",10.1021/acs.joc.0c00617,2020-07-09,0.6325673052707572
Synthesis,"Synthesis of Norpandamarilactonines, Pandamarilactonines, and Pandanamine","A facile route to naturally occurring (±)-norpandamarilactonines A and B, (±)-pandamarilactonines A-D, and pandanamine has been described from 3-methylfuran-2(5H)-one, with a reductive intramolecular aza-Michael-type addition as the key step.",10.1055/s-2008-1072534,2008-04-25,0.6325508091640967
Tetrahedron,Asymmetric synthesis of a potent azepanone-based inhibitor of the cysteine protease cathepsin K,,10.1016/j.tetlet.2005.02.145,2005-03-16,0.6325296299990197
Synlett,"Efficient Synthesis of Valsartan, a Nonpeptide Angiotensin II Receptor Antagonist","A highly efficient and convergent approach to the synthesis of the angiotensin II receptor antagonist valsartan (1), one of the most important agents used in anti h yperten sive therapy today, is described. Directed ortho-metalation of 4-bromotoluene provides the key boronic acid intermediate II which was subjected to palladium-catalyzed Suzuki coupling. This method overcomes many of the drawbacks associated with the previously reported syntheses. The saponification of the methyl ester in valsartan was realized in a convenient and economical manner, which is more suitable for industrial production.",10.1055/s-2006-926234,2006-02-06,0.632522060433693
Organic Process Research & Development,A Scaleable Synthesis of Fiduxosin,"Fiduxosin ( 1 ) has been under development at Abbott Laboratories for the treatment of benign prostatic hyperplasia. A convergent strategy required methodologies for preparation of an enantiomerically pure 3,4- cis -disubstituted pyrrolidine and a 2,3,5-trisubstituted thienopyrazine in a regiospecific manner. A [3+2] cycloaddition of an enantiopure azomethine ylide followed by a diastereoselective crystallization was employed to prepare the benzopyranopyrrolidine in high diastereomeric and enantiomeric purity. Conditions for reduction of an O-aryl lactone susceptible to epimerization were developed, and cyclization of the alcohol/phenol to the ether was accomplished in high yield. The thienopyrazine was prepared by condensation of methyl thioglycolate and a regiospecifically prepared 2-bromo-3-cyano-5-phenylpyrazine. Conditions for effective halogen substitutive deamination to prepare regiospecific trisubstituted pyrazines will be described.",10.1021/op049889k,2004-10-16,0.6325104980778887
Synthesis,Total Synthesis of Siccayne,"All articles of this category The palladium-catalyzed C - C coupling of 2-bromohydroquinone bis(methoxymethyl ether) with 2-methyl-3-butyn-2-ol is a key step in the six-step synthesis of the natural product siccayne [4-(2,5- dihydroxyphenyl)-2-methyl-1-buten-3-yne] from 1,4-benzoquinone.",10.1055/s-1990-27058,1990-01-01,0.6325044827473529
Journal of Organic Chemistry,Formal Synthesis of Anticoagulant Drug Fondaparinux Sodium,"The practical formal synthesis of the anticoagulant drug fondaparinux sodium 1 was accomplished using an optimized modular synthetic strategy. The important pentasaccharide 2, a precursor for the synthesis of fondaparinux sodium, was synthesized on a 10 g scale in 14 collective steps with 3.5% overall yield from well-functionalized monosaccharide building blocks. The strategy involved a convergent [3 + 2] coupling approach, with excellent stereoselectivity in every step of glycosylation from the monosaccharide building blocks. Efficient routes to the syntheses of these fully functionalized building blocks were developed, minimizing oligosaccharide stage functional-group modifications. The syntheses of all building blocks avoided rigorous reaction conditions and the use of expensive reagents. In addition, common intermediates and a series of one-pot reactions were employed to enhance synthetic efficiency, improving the yield considerably. In the monosaccharide-to-oligosaccharide assembly reactions, cheaper activators (e.g., NIS/TfOH, TESOTf, and TfOH) were used to facilitate highly efficient glycosylations. Furthermore, crystallization of several monosaccharide and oligosaccharide intermediates significantly simplified purification procedures, which would be greatly beneficial to the scalable synthesis of fondaparinux sodium.",10.1021/acs.joc.5b02468,2015-12-10,0.6325000710678107
Journal of Organic Chemistry,"Regioselective 6-Endo Cyclizations of 2-Indolylacyl Radicals:  Total Synthesis of the Pyrido[4,3-<i>b</i>]carbazole Alkaloid Guatambuine","A regioselective 6-endo reductive cyclization of 2-indolylacyl radicals constitutes the key step of a straightforward synthetic entry to the olivacine skeleton, illustrated by a total synthesis of the tetrahydropyridine alkaloid guatambuine.",10.1021/jo052428s,2006-01-12,0.6324989301273667
Angewandte Chemie International Edition,Total Synthesis of Ciguatoxin,Something fishy: Ciguatoxin (see structure) is one of the principal toxins involved in ciguatera poisoning and the target of a total synthesis involving the coupling of three segments. The key transformations in this synthesis feature acetylene-dicobalthexacarbonyl complexation.,10.1002/anie.200805996,2009-03-17,0.6324978835106837
Journal of Organic Chemistry,Total Synthesis of Laetevirenol A,The first complete synthesis of laetevirenol A was performed in nine steps via intramolecular Friedel-Crafts alkylation in a trans-selective manner. The key phenanthrene intermediate was synthesized by a one-pot Suzuki-Miyaura coupling and an aldol condensation cascade reaction.,10.1021/jo301345a,2012-09-04,0.6324957691740745
European Journal of Organic Chemistry,Synthesis of 6‐Substituted 2(1<i>H</i>)‐Pyridon‐3‐yl <i>C</i>‐2′‐Deoxyribonucleosides,"Abstract Two approaches to the synthesis of the title 6‐substituted 2(1 H )‐pyridon‐3‐yl C ‐2′‐deoxyribonucleosides have been pursued. A protected 6‐aminopyridine C ‐nucleoside intermediate was converted into the N ‐oxide followed by Ac 2 O‐mediated rearrangement and final deprotection to give 6‐acetylamino‐2‐oxo(1 H )‐pyridin‐3‐yl deoxyribonucleoside. Due to the unusually high stability of the N ‐acetyl group, the full deprotection was unsuccessful. In the second approach, 6‐chloro‐2‐pyridone was converted into phosphorodiamidate, which underwent ortho ‐magnesiation and iodination to give the 3‐iododerivative. It was then used in a Heck coupling with a sugar glycal and the resulting product deprotected to give 6‐chloro‐2‐oxo(1 H )‐pyridin‐3‐yl deoxyribonucleoside, which was either directly or after reprotection converted into 6‐methyl‐, 6‐amino‐, and 6‐unsubstituted pyridone C ‐nucleosides. The final nucleosides were very unstable and easily epimerized and/or oxidized, which limits (but not excludes) their further use in chemical biology.",10.1002/ejoc.201101662,2012-02-03,0.6324878926843561
Angewandte Chemie International Edition,Synthesis of the C<sub>18</sub>‐Norditerpenoid Alkaloid Neofinaconitine: A Lesson in Convergent Synthesis Planning,Hexacyclic framework: The total synthesis of the complex C18 -norditerpenoid alkaloid neofinaconitine has been achieved by a convergent approach. This remarkable synthesis featured two Diels-Alder cycloadditions and subsequent Mannich-type N-acyliminium and radical cyclizations to establish the unique hexacyclic core structure of the target molecule.,10.1002/anie.201309201,2013-12-06,0.632467607061129
Organic Letters,An Efficient Formal Synthesis of (−)-Clavosolide A Featuring a “Mismatched” Stereoselective Oxocarbenium Reduction,The enantioselective formal synthesis of the polyketide marine natural product (-)-clavosolide A is presented. The construction of the beta-C-glycoside subunit is highlighted by a one-pot oxocarbenium cation formation/reduction sequence. Yamaguchi dimerization afforded the diolide aglycon in 18 steps (longest linear sequence).,10.1021/ol8028302,2009-01-06,0.6324649652054333
Angewandte Chemie International Edition,A Concise Total Synthesis of (−)‐Berkelic Acid,"Reported here is a concise total synthesis of (-)-berkelic acid in eight linear steps. This synthesis features a Catellani reaction/oxa-Michael cascade for the construction of the isochroman scaffold, a one-pot deprotection/spiroacetalization operation for the formation of the tetracyclic core structure, and a late-stage Ni-catalyzed reductive coupling for the introduction of the lateral chain. Notably, four stereocenters are established from a single existing chiral center with excellent stereocontrol during the deprotection/spiroacetalization process. Stereocontrol of the intriguing deprotection/spiroacetalization process is supported by DFT calculations.",10.1002/anie.202014660,2020-11-30,0.632450153782736
Synthesis,Asymmetric Synthesis of (+)- and (-)-Wuweizisu C Stereoisomers and Their Chemosensitizing Effects on Multidrug-Resistant Cancer Cells,"Total syntheses of the dibenzocyclooctadiene natural product wuweizisu C in its (-)-form [(S)-1] and its (+)-form [(R)-1] were achieved in 19 steps, starting from commercially available gallic acid. In the key step, the asymmetric biphenyl axis was constructed by an oxazoline-mediated Ullmann reaction to provide either the P or M biaryl product in 68% yield and >99% de, depending on the configuration of the oxazoline. The efficiency of this total synthesis was excellent, as the syntheses of (S)-1 and (R)-1 from intermediate 7 each proceeded in 13 steps with an overall yield of 6.8%. (S)-1 and (R)-1 were evaluated as chemosensitizers for multidrug-resistant cancers.",10.1055/s-0029-1216981,2009-08-28,0.6324392523745505
Journal of Organic Chemistry,A Short and Economical Synthesis of Orthogonally Protected<i>C</i>-Linked 2-Deoxy-2-acetamido-α-<scp>d</scp>-galactopyranose Derivatives,"A short and high-yielding synthesis has been devised to prepare C-linked 2-deoxy-2-acetamido-alpha-D-galactopyranose derivative 3. One of the main advantages of this approach is that it employs commercially available and inexpensive d-glucosamine as the starting material. The key steps include a highly stereoselective C-allylation followed by epimerization of the C-4 hydroxyl group. Building block 3 and orthogonally protected C-linked 2-deoxy-2-acetamido-alpha-D-galactopyranose derivative 2 were obtained in 44% overall yield (six steps) and 29% overall yield (eight steps), respectively. This represents a significant improvement over previously reported syntheses.",10.1021/jo051938j,2006-04-01,0.6324303822326635
Tetrahedron,A convergent approach to the synthesis of aprepitant: a potent human NK-1 receptor antagonist,,10.1016/j.tetlet.2007.09.051,2007-09-13,0.6324194699561047
Synthesis,Practical Asymmetric Synthesis of Hastanecine and Dihydroxyheliotridane by a Claisen Rearrangement/Amine-Epoxide-Opening Sequence,"All articles of this category A practical 13-step synthesis of the title compounds suitable for the gram scale has been developed. Key steps are Sharpless resolution, Claisen rearrangement, epoxidation and intramolecular S N 2 ring closure to form the pyrrolizidine system.",10.1055/s-1993-25913,1993-01-01,0.6324065922538079
Organic Process Research & Development,"Developing an Asymmetric Transfer Hydrogenation Process for (<i>S</i>)-5-Fluoro-3-methylisobenzofuran-1(3<i>H</i>)-one, a Key Intermediate to Lorlatinib","Synthesis of ( S )-5-fluoro-3-methylisobenzofuran-1(3 H )-one ( 6 ), a key intermediate to lorlatinib, is described. A few synthetic methodologies, that is, boron reduction, enzymatic reduction, asymmetric hydrogenation, and asymmetric transfer hydrogenation, were evaluated for the chiral reduction of the substituted acetophenone intermediate ( 8 ). A manufacturing process, on the basis of the asymmetric transfer hydrogenation, was developed. This process was successfully scaled up to prepare 400 kg of 6 .",10.1021/acs.oprd.7b00187,2017-07-05,0.6323988825105451
Organic Letters,Synthesis and Assignment of Absolute Configuration of the Iridoid 9-Deoxygelsemide,"The first enantioselective synthesis of 9-deoxygelsemide, belonging to a rare group of iridoids isolated from Gelsemium plants, is described. The key synthetic steps are a variant of the Woodward-Prevost reaction to install the characteristic cis-alpha-1,2-dioxygenated system at C-6 and C-7 with complete diastereoselectivity. Construction of the dihydropyran ring was achieved via formylation of lactone I, followed by dehydration of the corresponding lactol. The synthesis allowed assignment of absolute configuration to 9-deoxygelsemide and related iridoids.",10.1021/ol902809v,2009-12-28,0.6323774482444653
Journal of the American Chemical Society,Enantioselective Total Synthesis of (−)-Daphenylline,"A concise enantioselective total synthesis of (−)-daphenylline, a hexacyclic Daphniphyllum alkaloid with a unique benzene ring, was achieved in 14 steps. The synthesis commences with two chiral stereocenters, C2 and C18, readily installed via Carreira’s Ir/amine dual-catalyzed allylation. The allylic bridgehead amine 6 was rapidly prepared through Wickens’ photoredox-catalyzed hydrocarboxylation of olefin and CuBr 2 -catalyzed α-amination of ketone. The tetracycle 4 was formed via Pd-catalyzed reductive Heck reaction or, more concisely, by Krische’s Rh-catalyzed reductive 1,6-enyne cyclization. In this synthesis, newly reported Wickens’ photoredox-catalyzed hydrocarboxylation was used twice, and Friedel–Crafts acylation thrice.",10.1021/jacs.3c12741,2024-01-05,0.6323749256384235
Tetrahedron,Simple synthetic route to chrysanthemic acid and hemicaronic aldehyde,,10.1016/s0040-4039(01)86870-2,1979-01-01,0.6323674625300076
Angewandte Chemie International Edition,A Synthetic Pathway to Either Enantiomer of Merrilactone A,A route to enantioenriched merrilactone A was found via intermediate 3. A degradation pathway in which meso compound 1 is transformed into key intermediate 2 in four steps occurs with full regiocontrol and promising enantiocontrol. A key feature of this reaction sequence is the desymmetrization of 1 through an intramolecular asymmetric ring-opening reaction.,10.1002/anie.200462509,2005-02-02,0.6323476245137843
Tetrahedron,"A practical synthesis of N,N-dimethyl-(6-arylpyrid-2-yl)alkylamines",,10.1016/j.tetlet.2010.08.069,2010-08-25,0.6323465803391367
Synthesis,"Synthesis of 2-(1-Hydroxy-2-phenylethyl)-cyclohexanone and Derivatives Thereof. A New Synthesis of 1,8-Dimethylphenanthrene",,10.1055/s-1977-24346,1977-01-01,0.6323368836069125
Tetrahedron,"Synthetic studies on oxetanocin, a novel nucleoside with an oxetane ring synthesis of some chiral D-oxetanosyl acylates",,10.1016/s0040-4039(00)80595-x,1988-01-01,0.6323268308302189
Synlett,"Efficient Synthesis of Clitocine via 1,3-<i>N</i> (<i>endo</i>) to <i>N</i> (<i>exo</i>) Migration: A Revision to Kini’s Work","Efficient synthesis of clitocine has been accomplished via unprecedented 1,3-N (endo) to N (exo) migration as a key transformation. Incorporation of p-chlorobenzoyl (PCB) group as a protecting group led to the easy solidification of the intermediate of 7, thus making the isolation very facile and to the minimization of the epimerization of the anomeric center at the final deprotection stage.",10.1055/s-2005-871564,2005-07-04,0.6323164069074511
Organic Letters,Synthesis of the Cyclohexan Subunit of Baconipyrones A and B from Furan,[figure: see text] The synthesis of the cyclohexan subunit of the siphonarlid metabolites baconipyrones A and B from furan is described. A key step included the alkylative ring opening of 7-oxanorbornenic sulfone 4 and oxidative desulfonylation of compound 8.,10.1021/ol000334t,2000-12-14,0.6323153227462669
Organic Letters,"Isolation and Bioinspired Total Synthesis of Rugosiformisin A, A Skeleton-Rearranged Abietane-Type Diterpenoid from <i>Isodon rugosiformis</i>","Rugosiformisin A, a skeleton-rearranged abietane-type diterpenoid with a spiro[4.5]decane motif, was isolated from Isodon rugosiformis . Its structure was unambiguously established via NMR spectroscopic analysis and single-crystal X-ray diffraction. A bioinspired asymmetric synthesis of rugosiformisin A was achieved in 15 steps with 2.7% overall yield. The synthesis features an iridium-catalyzed asymmetric polyene cyclization and a semipinacol rearrangement.",10.1021/acs.orglett.2c02834,2022-10-26,0.6323152241858172
Tetrahedron,"Synthetic studies on palytoxin. Stereocontrolled, practical synthesis of the C.101–C.115 segment",,10.1016/s0040-4039(00)85616-6,1982-01-01,0.632285655027472
Journal of Organic Chemistry,Convergent Approach to the Tetracyclic Core of the Apparicine Class of Indole Alkaloids via a Key Intermolecular Nitrosoalkene Conjugate Addition,"Readily available methyl 3-formylindol-2-ylacetate and N-tosyl-4-chloro-3-piperidone oxime have been used to construct the tetracyclic skeleton of the apparicine class of monoterpene indole alkaloids in only four steps in 80% overall yield. Key transformations in this convergent approach involve use of an intermolecular ester enolate/nitrosoalkene conjugate addition to form the C-15/16 bond, followed by a reductive cyclization to construct the C-ring of the tetracycle.",10.1021/jo501067u,2014-06-13,0.6322771667253904
Tetrahedron,Synthesis of macrocyclic terpenoids by intramolecular cyclization VI. Synthesis of 3Z-cembrene A and cembrenene,,10.1016/s0040-4039(01)82931-2,1981-01-01,0.6322736733512144
Journal of the American Chemical Society,Total Synthesis of Bryostatin 1,"Bryostatin 1 is a marine natural product that is a very promising lead compound because of the potent biological activity it displays against a variety of human disease states. We describe herein the first total synthesis of this agent. The synthetic route adopted is a highly convergent one in which the preformed, heavily functionalized pyran rings A and C are united by ""pyran annulation"", the TMSOTf-promoted reaction between a hydroxyallylsilane appended to the A-ring fragment and an aldehyde contained in the C-ring fragment, with concomitant formation of the B ring. Further elaborations of the resulting very highly functionalized intermediate include macrolactonization and selective cleavage of just one of five ester linkages present.",10.1021/ja110198y,2010-12-22,0.6322655674296396
Angewandte Chemie International Edition,Asymmetric Total Synthesis of Cephanolide A,"dinorditerpenoid from cephalotaxus sinensis, was achieved. The synthesis features a convergent strategy, which provides a flexible approach to prepare the biogenetically cephalotaxus diterpenoids and structurally related derivatives for biological studies. A mild intramolecular Prins cyclization was developed to construct the central hexahydrofluorenol skeleton (A-B-C ring), which relies on the originally proposed hydroacylation strategy. A remote hydroxy group directed hydrogenation was applied to stereospecifically reduce the tetra-substituted enone unit. A sequence of ring forming steps, including lactonization, cation mediated etherification and Friedel-Crafts cyclization, was efficiently utilized to forge the cage-like skeleton.",10.1002/anie.202009562,2020-08-04,0.6322464741109692
Synlett,Total Synthesis of Lipogrammistin-A: Efficient Macrocyclization with 2-Nitrobenzenesulfonamide,"All articles of this category Total synthesis of lipogrammistin-A ( 1 ) was accomplished using a 2-nitrobenzenesulfonyl (Ns) group for both protection and activation of amines. The β-amino ester derivative 16 was synthesized from carboxylic acid 12 in six steps by way of reduction to the aldehyde and the subsequent Wittig olefination. N -Alkylation of the Ns group under Mitsunobu conditions followed by amide formation provided 20 . Intramolecular alkylation of the Ns group in 20 gave the 18-membered ring 21 as the exclusive product. After removal of the Ns group, selective acylation of the two of the three amino groups with ( S )-2-methylbutyric acid furnished the desired compound 1 . lipogrammistin-A - 2-nitrobenzenesulfonamide - nosyl group (Ns) - macrocyclization - alkylation - Mitsunobu reaction",10.1055/s-2000-7950,2000-01-01,0.6322333072058632
Journal of the American Chemical Society,Enantioselective Total Synthesis of (−)-Zygadenine,"The Veratrum alkaloids are highly complex steroidal alkaloids characterized by their intricate structural and stereochemical features and exhibit a diverse range of pharmacological activities. A new synthetic pathway has been developed to access this family of natural products, which enabled the first total synthesis of (−)-zygadenine. This synthetic route entails the construction of a hexacyclic carbon skeleton through a stereoselective intramolecular Diels–Alder reaction, followed by a radical cyclization. Subsequently, a meticulously designed sequence of redox manipulations was optimized to achieve the de novo synthesis of this highly oxidized Veratrum alkaloid.",10.1021/jacs.3c08039,2023-09-08,0.6322317736804584
Journal of Organic Chemistry,Alternative Syntheses of (<i>S</i>)-cEt-BNA: A Key Constrained Nucleoside Component of Bioactive Antisense Gapmer Sequences,"Approaches to the synthesis of the constrained 5-methyluracil nucleoside (S)-cEt-BNA, a key ""gapmer"" unit in a number of biologically relevant antisense oligonucleotides, are described using 5-methyluridine as starting material. In the shorter synthesis, a nine-step linear sequence afforded a O-protected (S)-cEt-BNA consisting of a [2.2.1]dioxabicycloheptane core in 7% overall yield. A competing reaction in an intramolecular cyclization of a tosylate led to a bicyclic oxetane.",10.1021/jo502320y,2014-11-17,0.6322272352714736
Organic Process Research & Development,Evolution of a Green and Sustainable Manufacturing Process for Belzutifan: Part 1─Process History and Development Strategy,"An improved synthesis has been developed for belzutifan, a novel HIF-2α inhibitor for the treatment of Von Hippel–Lindau (VHL) disease-associated renal cell carcinoma (RCC). The efficiency of previous supply and commercial routes was encumbered by a lengthy 5-step sequence, needed to install a chiral benzylic alcohol by traditional methods. Identification and directed evolution of FoPip4H, an iron/α-ketoglutarate dependent hydroxylase, enabled a direct enantioselective C–H hydroxylation of a simple indanone starting material. While this enabling transformation set the stage for a greatly improved synthesis, several other key innovations were made including the development of a base-metal-catalyzed sulfonylation, a KRED-catalyzed dynamic kinetic resolution, and a facile S N Ar reaction in water. Together, these improvements resulted in a significantly shorter synthesis (9 steps) versus the supply route (16 steps) and a 75% reduction in process mass intensity (PMI), while also removing the reliance on third-row transition metals and toxic solvents.",10.1021/acs.oprd.3c00408,2024-02-05,0.6322191291058723
Tetrahedron,"A Practical Synthesis of Chiral 3-Chloro-2-hydroxyalkanoates and 2,3-Epoxyalcohols",,10.1016/s0040-4039(00)96187-2,1987-01-01,0.6322063731838274
Organic Process Research & Development,"Enantioselective Synthesis of (1<i>R</i>,2<i>S</i>)-1-Amino-2-vinylcyclopropanecarboxylic Acid Ethyl Ester (Vinyl-ACCA-OEt) by Asymmetric Phase-Transfer Catalyzed Cyclopropanation of (<i>E</i>)-<i>N</i>-Phenylmethyleneglycine Ethyl Ester","A concise asymmetric synthesis of (1 R,2 S )-1-amino-2-vinylcyclopropanecarboxylic acid ethyl ester, a key intermediate in the preparation of many hepatitis C virus inhibitors, is described. Stereoselective cyclopropanation of ( E )- N -phenylmethyleneglycine ethyl ester was effected by treatment with trans -1,4-dibromo-2-butene in the presence of a catalytic amount of a chiral phase-transfer catalyst. Microscale high-throughput experimentation techniques were successfully used to identify a cinchonidine-derived catalyst that provided (1 R,2 S )-1-( E )- N -phenylmethyleneamino-2-vinylcyclopropanecarboxylic acid ethyl ester in up to 84% ee. This was translated to a lab scale process to attain 78% yield and 77.4% ee. Chiral purity upgrade and isolation of the ester was accomplished via preparatory supercritical fluid chromatography followed by crystallization of the ester as its tosylate salt. The improved synthesis described herein represents a potentially more economical preparation of this valuable intermediate.",10.1021/op100070d,2010-04-07,0.6321973982995912
Synlett,"Novel Exocyclic Nucleoside Related to Clitocine: A Convergent Synthesis of 3′-Azido-2′,3′-dideoxy Clitocine","The synthesis of a new clitocine derivative was achieved through a convergent strategy. A protected 4,6-diamino-5-nitro­pyrimidine was condensed with p-chlorobenzoyl (PCB)-protected methyl 3′-azido-2′,3′-dideoxyribofuranoside, followed by subsequently deprotection to give the desired product.",10.1055/s-0030-1258503,2010-07-16,0.6321695109744759
Synlett,Total Synthesis of Achaetolide from d-Mannitol,"A highly convergent stereoselective total synthesis of achaetolide, a ten-membered lactone is described. The ring-closing metathesis reaction was used to construct the macrocycle and E-olefinic moiety in the molecule. The key acid and alcohol fragments were synthesized from a single chiral pool material d-mannitol.",10.1055/s-0030-1259056,2010-11-19,0.6321666750353354
Tetrahedron,An alternative synthesis of Vandetanib (Caprelsa™) via a microwave accelerated Dimroth rearrangement,"Vandetanib is an orally available tyrosine kinase inhibitor used in the treatment of cancer. The current synthesis proceeds via an unstable 4-chloroquinazoline, using harsh reagents, in addition to requiring sequential protection and deprotection steps. In the present work, use of the Dimroth rearrangement in the key quinazoline forming step enabled the synthesis of Vandetanib in nine steps (compared to the previously reported 12–14).",10.1016/j.tetlet.2017.02.082,2017-03-01,0.6321583372123719
Journal of Organic Chemistry,"Concise Enantiospecific, Stereoselective Syntheses of (+)-Crispine A and Its (−)-Antipode","An enantiospecific and stereoselective total synthesis of the natural product (+)-crispine A has been demonstrated employing a Pictet-Spengler bis-cyclization reaction between commercially available (R)-(-)-methyl 2-amino-3-(3,4-dimethoxyphenyl)propanoate and 4-chloro-1,1-dimethoxybutane to preferentially provide the cis tricyclic adduct. Decarboxylation by a convenient two-step protocol provided the enantiopure natural product in three steps with an overall isolated yield of 32% from the amino acid. The unnatural antipode (-)-crispine A was similarly prepared in three steps from the commercially available (S)-(+)-amino acid.",10.1021/jo102112k,2011-02-22,0.6321575516196948
Tetrahedron,Synthetic studies on manzamine A: An efficient synthesis of the bicyclic compound leading to the formation of the tetracyclic ABCE ring subunit I (I),,10.1016/s0040-4039(98)00278-0,1998-04-01,0.6321523666231124
Angewandte Chemie International Edition,Second‐Generation Total Synthesis of Spirastrellolide F Methyl Ester: The Alkyne Route,"Outlandish: The spiroketal embedded in spirastrellolide F methyl ester is a daring site for ring closure, yet it has allowed the power of catalytic alkyne scission and activation to be showcased (see scheme). An improved strategy for the introduction of the labile side chain was also developed.",10.1002/anie.201103270,2011-07-26,0.6321411441754232
European Journal of Organic Chemistry,Asymmetric Formal Synthesis of (–)‐Swainsonine by a Highly Regioselective and Diastereoselective Allylic Amination Using Chlorosulfonyl Isocyanate,"Abstract A concise asymmetric formal synthesis of (–)‐swainsonine from readily available D ‐erythronolactone is described. The key steps include a highly diastereoselective amination of a chiral benzylic ether, which occurs with the retention of stereochemistry using chlorosulfonyl isocyanate, and a palladium‐catalyzed decarboxylative N ‐allylation of an allyl carbamate.",10.1002/ejoc.201300308,2013-05-31,0.6321354246088922
Tetrahedron,Efficient synthesis of deoxyribonucleotide phosphorothioates by the use of DMT cation scavenger1,,10.1016/00404-0399(50)1346-j,1995-09-01,0.6321195117078151
Angewandte Chemie International Edition,Total Synthesis of (−)-Tetrazomine and Determination of Its Stereochemistry,"A new method for the formation of the allylic amine precursor to an azomethine ylide 1 has been developed and exploited in an efficient 1,3-dipolar cycloaddition to afford the key tetracyclic intermediate used in the synthesis of (-)-tetrazomine (2). Bn=benzyl.",10.1002/1521-3773(20010417)40:8<1463::aid-anie1463>3.0.co;2-8,2001-04-17,0.6321163618986937
Journal of the American Chemical Society,Total Syntheses of (+)- and (−)-Tetrapetalones A and C,Described herein are syntheses of the naturally occurring polyketides (-)-tetrapetalones A and C and their respective enantiomers. The employed strategy involves initial assembly of a masked N-aryl tetramic acid which is advanced via a highly selective conjugate addition/intramolecular Friedel-Crafts acylation sequence to deliver a key azepine intermediate. Application of recently developed C-H activation chemistry and subsequent Heck cyclization delivers the aglycone framework in an overall 12 steps. Resolution of the aglycone via stereospecific glycosylation with an enantiopure glycosyl donor followed by separation of the derived diastereomers enables further advancement to either (+)- or (-)-tetrapetalones A and C.,10.1021/jacs.7b09358,2017-10-09,0.6321139110763068
Organic Process Research & Development,"Development of a Safe and Practical Synthesis of Enantiomerically Pure (<i>S</i>)- and (<i>R</i>)-<i>N</i>-Boc-3-(Trifluoromethyl)piperazines Enabled by Aza-Michael Addition of Optically Pure 4-Phenyl-2-Oxazolidinone to 3,3,3-Trifluoro-1-Nitropropene","( S )- and ( R )- N -Boc-3-(trifluoromethyl)piperazines are attractive building blocks for the rational design of drugs. Until now, their chiral syntheses were unknown. Exploration of three synthetic approaches via chiral 3,3,3-trifluoropropane-1,2-diamines yielded a scalable route that has been used for multigram synthesis. Two routes were not amendable for scale-up due to low yielding, tedious purification, limited availability of reagents, and safety issues. The successful and practical route relied on a modified process to mitigate the safety issues for the synthesis of ( E )-3,3,3-trifluoro-1-nitroprop-1-ene, which was used as a stock solution for the highly diastereoselective aza-Michael addition of optically pure 4-phenyl-2-oxazolidinone. Boc protection of an amino group allowed subsequent transformations to chiral N -Boc-protected 3,3,3-trifluoropropane-1,2-diamine under mild conditions, without the need for chiral chromatography. The amidation of chiral N -Boc-protected 3,3,3-trifluoropropane-1,2-diamine with 2-chloroacetyl chloride, followed by intramolecular cyclization and subsequent reduction afforded enantiomerically pure N -Boc-3-(trifluoromethyl)piperazines.",10.1021/acs.oprd.4c00289,2024-07-30,0.632106539927148
Tetrahedron,First asymmetric total synthesis of novel and cytotoxic 2′-R-hydroxylanneaquinol,,10.1016/j.tetlet.2008.09.076,2008-09-19,0.6321041475316713
Tetrahedron,Synthesis of an abiotic ditopic receptor molecule,,10.1016/s0040-4039(01)81438-6,1984-01-01,0.6321004291354994
Tetrahedron,An efficient synthesis of δ-amino[3-13C]levulinic acid,,10.1016/s0040-4039(02)01970-6,2002-11-01,0.6320894142591396
Journal of Organic Chemistry,Total Synthesis of the Marine Polyketide (−)-Gracilioether F,"First asymmetric synthesis of the marine natural product (-)-gracilioether F is described from a d-mannitol derived known compound. The key step involves intramolecular 1,4-conjugate addition of a hydroxymethyl radical generated from Ti (III) mediated ring opening of a terminal epoxy ring tethered to a butenolide to produce stereoselectively a five-membered ring fused bicyclic lactone, the core structure present in gracilioether F.",10.1021/acs.joc.7b01179,2017-06-21,0.6320853918964521
Tetrahedron,"Stereoselective synthesis of (2S)-2-hydroxymethylglutamic acid, a potent agonist of metabotropic glutamate receptor mGluR3",,10.1016/s0040-4039(01)02196-7,2002-01-01,0.632085250862797
Synlett,A Synthetic Approach to 3-Substituted Cephalosporins: A New synthesis of 3-Chloro-3-Cephem,"All articles of this category An efficient approach to the synthesis of 3-chloro-3-cephem (Cefaclor), starting from the parent mesyloxy derivative is reported. The substitution is postulated to take place via an intermediate cyclic allene.",10.1055/s-1994-22811,1994-01-01,0.6320623846738234
Organic Process Research & Development,Development of a Pilot Scale Process for the Anti-Alzheimer Drug (−)-Galanthamine Using Large-Scale Phenolic Oxidative Coupling and Crystallisation-Induced Chiral Conversion,"(−)-Galanthamine has been synthesised using an efficient nine-step procedure, which in large scale affords 12.4 (6.7−19.1)% overall yield. The process improvements and optimization of each step are described. Notable steps include (i) an oxidative phenol coupling and (ii) crystallisation-induced chiral conversion of (±)-narwedine to (−)-narwedine. This is a practical and cost-effective synthesis of (−)-galanthamine which is amenable to pilot plant scale-up to afford sufficient material for use in clinical trials.",10.1021/op990019q,1999-11-01,0.6320537785804593
Journal of Organic Chemistry,Total Syntheses of Bengamides B and E,"Total syntheses of the cytotoxic marine natural products bengamides B and E are described. Both bengamides are prepared via amide coupling of a protected polyhydroxylated lactone intermediate 9 with a suitably substituted aminocaprolactam intermediate. Lactone 9 is prepared in five steps from commercially available alpha-D-glucoheptonic gamma-lactone. The key reactions are a selective deprotection of a 1,2-acetonide in the presence of a 1,3-acetonide and an (E)-selective olefination of an unstable aldehyde using a gem-dichromium reagent. The bengamide B lactam intermediate 10 is prepared in seven steps from commercially available (5R)-5-hydroxy-L-lysine (12). The desired S-configuration at the gamma-OH lactam position is established using the Mitsunobu reaction.",10.1021/jo0017133,2001-02-24,0.6320491862782808
Journal of Organic Chemistry,"Utilizing Native Directing Groups: Synthesis of a Selective I<sub>Kur</sub> Inhibitor, BMS-919373, via a Regioselective C–H Arylation","BMS-919373 is a highly functionalized quinazoline under investigation as a selective, potent I Kur current blocker. By utilizing the aminomethylpyridine side chain at C-4, a selective C–H functionalization at C-5 was invented, enabling the efficient synthesis of this molecule. The strategy of leveraging this inherent directing group allowed the synthesis of this complex heterocycle in only six steps from commodity chemicals. The scope of the C–H activation was further investigated, and the generality of the transformation across a series of bicyclic aromatic heterocycles was explored.",10.1021/acs.joc.8b02254,2018-11-05,0.6320453725463555
Synlett,Synthesis of Spirocyclic Imines: Key Pharmacophores in the Shellfish Toxins Spirolides and Gymnodimine,All articles of this category (opens in new window),10.1055/s-2003-41481,2003-01-01,0.6320393835562148
Angewandte Chemie International Edition,A Scalable Total Synthesis of the Antitumor Agents Et‐743 and Lurbinectedin,"An efficient and scalable approach is described for the total synthesis of the marine natural product Et-743 and its derivative lubinectedin, which are valuable antitumor compounds. The method delivers 1.6 % overall yield in 26 total steps from Cbz-protected (S)-tyrosine. It features the use of a common advanced intermediate to create the right and left parts of these compounds, and a light-mediated remote C-H bond activation to assemble a benzo[1,3]dioxole-containing intermediate.",10.1002/anie.201900035,2019-01-28,0.6320365925100947
Journal of Organic Chemistry,Practical Synthesis of 7-Prenylindole,"7-Prenylindole is a useful building block for natural product and natural product analogue synthesis. While there have been several past syntheses of 7-prenylindole, none of them is very practical for its preparation on scale. Using an aza-Claisen rearrangement as the key step, 7-prenylindole has been prepared in four steps from indoline in 62% overall yield.",10.1021/jo070734v,2007-06-20,0.6320300876924888
Journal of Organic Chemistry,Convergent Synthesis of PI3K Inhibitor GDC-0908 Featuring Palladium-Catalyzed Direct C–H Arylation toward Dihydrobenzothienooxepines,"A practical convergent synthesis of PI3K inhibitor GDC-0908 (1) is described. The process features a dihydrobenzothienooxepine formation via palladium-catalyzed intramolecular direct C-H arylation and a Negishi coupling to construct the key C-C bonds. We further developed a general synthesis of dihydrobenzothienooxepines in good to excellent yields via palladium-catalyzed intramolecular direct C-H arylation, which tolerates both electronically and sterically diverse substituents on the phenyl ring.",10.1021/acs.joc.8b02751,2018-12-13,0.6320071278676355
Organic Process Research & Development,Nitro-Aldol Approach for Commercial Manufacturing of Fenspiride Hydrochloride,"An efficient, short manufacturing process for fenspiride hydrochloride is reported. Nitro-aldol condensation is the key reaction in the developed process. Improved routes to key building blocks are demonstrated by expedient multikilogram production. Hazardous reactions are avoided. API produced following this new route meets the quality requirement NLT 99.70% purity by HPLC with any individual impurity NMT 0.10% with very good yield.",10.1021/acs.oprd.9b00022,2019-05-09,0.6320050195573393
Organic Process Research & Development,"Preparation of Saxagliptin, a Novel DPP-IV Inhibitor","The commercial-scale synthesis of the DPP-IV inhibitor, saxagliptin ( 1 ), is described from the two unnatural amino acid derivatives 2 and 3 . After the deprotection of 3, the core of 1 is formed by the amide coupling of amino acid 2 and methanoprolinamide 4 . Subsequent dehydration of the primary amide and deprotection of the amine affords saxagliptin, 1 . While acid salts of saxagliptin have proven to be stable in solution, synthesis of the desired free base monohydrate was challenging due to the thermodynamically favorable conversion of the free amine to the six-membered cyclic amidine 9 . Significant process modifications were made late in development to enhance process robustness in preparation for the transition to commercial manufacturing. The impetus and rationale for those changes are explained herein.",10.1021/op900226j,2009-10-16,0.6320016221354
Tetrahedron,"Reduction of 2,5-dialkylpyrrolines. A key step in a synthesis of natural insecticides",,10.1016/s0040-4039(01)80365-8,1989-01-01,0.6319950020295239
Organic Process Research & Development,Synthesis of 1-Chloronaloxone and 2-Chloronaloxone,"This paper describes the unambiguous synthesis of authentic samples of 1-chloronaloxone and 2-chloronaloxone to support the unequivocal assignment of impurities observed in a drug product containing a combination of buprenorphine hydrochloride and naloxone hydrochloride. The key step in the synthesis of 1-chloronaloxone was the C-1-selective chlorination of (5α)-6-(1,3-dioxolan-2-yl)-4,5-epoxy-14-hydroxy-3-methoxy-17-(2-propenyl)morphinan using the Palau’Chlor reagent. The key step in the synthesis of 2-chloronaloxone was the C-2-selective chlorination of (5α)-3-diethylcarbamate-6-(1,3-dioxolan-2-yl)-4,5-epoxy-14-hydroxy-17-(2-propenyl)morphinan using a directed ortho metalation approach.",10.1021/acs.oprd.1c00288,2021-10-15,0.6319841075077903
Journal of Organic Chemistry,Mitomycin Synthetic Studies:  Stereocontrolled and Convergent Synthesis of a Fully Elaborated Aziridinomitosane,"Full details of a stereocontrolled and convergent synthetic route to 9a-desmethoxymitomycin A (1) are reported. The target molecule possesses the parent tetrahydropyrrolo[1,2-a]indole ring system characteristic of the mitomycin family of antitumor agents. The synthesis was based on the diastereocontrolled addition of a fully elaborated cinnamylstannane to a pyrrolidine-based N-acyliminium ion as the key convergent step, which resulted in the installation of the C9 and C9a stereogenic centers.",10.1021/jo048924i,2004-09-23,0.6319834623844834
Synthesis,Scalable Synthesis of a New Dihydroxylated Intermediate for Tetrodotoxin and Its Analogues,"The synthesis of a novel intermediate for tetrodotoxin and its analogues, possessing two hydroxy groups at C-8 and C-11, is described. The procedure involves a Diels-Alder reaction between bromolevoglucosenone and a tert-butyldiphenylsilyl-protected isoprenol during which the C-11 group hydroxy is installed. Subsequent transformations, including an Overman rearrangement, affords a cyclohexene intermediate containing a trichloroacetamide moiety as a requisite amino functionality for installation of the guanidine unit present in tetrodotoxin. Hydroxylation at C-8 is carried out via neighboring group participation of the trichloroacet­amide to furnish the desired diol intermediate.",10.1055/s-0029-1218747,2010-04-19,0.6319663911439443
Journal of Organic Chemistry,"Practical Preparation of 3,3-Difluoropyrrolidine","A practical and cost-effective synthesis of 3,3-difluoropyrrolidine is reported. The synthesis involves the isolation of two intermediates, which are prepared via two efficient through processes: (1) a Claisen rearrangement followed by a Ru(VIII)-catalyzed oxidation to prepare the 2,2-difluorosuccinic acid and (2) an efficient cyclization to form N-benzyl-3,3-difluoropyrrolidinone followed by BH(3).Me(2)S reduction.",10.1021/jo050591h,2005-06-24,0.6319658977590624
Organic Letters,Stereoselective Approach to the Core Structure of (+)-Phainanoid A via Strategically Engineered Cascade Polyene Cyclization,"Stereoselective synthesis of 3b and its cascade polyene cyclization to 18b have been described. Acyclic polyene 3b was prepared from allyl bromide 4 and 1,3-dithiane 5, and intermediates 4 and 5 were synthesized from the commercially available geraniol ( 6 ) and cyclopenten-2-one ( 8 ), respectively, using enantioselective reduction of ketone, Johnson–Claisen rearrangement, and the Suzuki reaction as key steps. Au(I)-mediated diastereoselective polyene cyclization of 3b efficiently afforded tetracyclic compound 18b .",10.1021/acs.orglett.4c02948,2024-09-18,0.6319638018966472
Journal of the American Chemical Society,Convergent Total Synthesis of Gymnocin-A and Evaluation of Synthetic Analogues,"The first total synthesis of gymnocin-A (1), a cytotoxic polycyclic ether isolated from a notorious red tide dinoflagellate, Karenia mikimotoi, has been accomplished. The synthesis relies heavily on the Suzuki-Miyaura cross-coupling-based methodology to assemble the tetradecacyclic polyether skeleton. Convergent union of the GHI (5) and KLMN (6) rings, both of which were prepared from a common intermediate 7, and the subsequent ring closure of the J ring delivered the GHIJKLMN ring. The crucial coupling between the ABCD and FGHIJKLMN ring fragments (3 and 4, respectively) and stereoselective installation of the C17 hydroxyl group, followed by cyclization of the E ring gave rise to the tetradecacyclic polyether skeleton 2. Finally, incorporation of the 2-methyl-2-butenal side chain completed the total synthesis of gymnocin-A. The convergent nature of the synthesis, which employs three fragments of comparable complexity, is well-suited for preparation of various structural analogues of gymnocin-A to explore the structure-activity relationship. The results of preliminary structure-activity relationship studies of several synthetic analogues are also provided.",10.1021/ja042686r,2005-03-01,0.631961729562172
Organic Letters,Synthesis of the Putative Structure of (±)-Amarbellisine,"The title compound was synthesized mainly by palladium catalytic coupling, cyclopropyl ring-opening rearrangement, epoxidation, Swern oxidation, demethanol reactions, and selective reduction. This synthesis was achieved in 16 steps with 9.7% overall yield. Unfortunately, the published spectroscopic data do not match with those of our synthetic compound.",10.1021/ol3034093,2012-12-28,0.6319558601796206
Angewandte Chemie International Edition,A Convergent Route to the <i>Galbulimima</i> Alkaloids (−)‐GB 13 and (+)‐GB 16,Alkaloids all round: A 19-step total synthesis of the galbulimima alkaloid (−)-GB 13 starting from commercially available starting material and the first total synthesis of the galbulimima alkaloid (+)-GB 16 have been achieved (see scheme; Boc=tert-butoxycarbonyl).,10.1002/anie.201002299,2010-07-13,0.6319498014418967
Journal of Organic Chemistry,Scalable 9-Step Synthesis of the Splicing Modulator NVS-SM2,"NVS-SM2, the first activator of pre-mRNA splicing, displays remarkable pharmacological in vivo activities in models of spinal muscular atrophy. Herein we describe an improved approach to the synthesis of this compound, which features a convenient introduction of sterically encumbered amine moiety onto a fluoropyridazine intermediate.",10.1021/acs.joc.7b03009,2018-02-08,0.631939007817642
Organic Process Research & Development,Total Synthesis of (+)-Oxo-tomaymycin,"(+)-Oxo-tomaymycin, a naturally occurring substance of the pyrrolo-1,4-benzodiazepine family, was synthesized using a short and efficient route. The key construction of the seven-membered ring by amide bond formation was realized via a chemoselective Ar-NO 2 reduction using TiCl 3 under acidic conditions, followed by a spontaneous cyclization. This synthesis was easily scaled up to 80 g, and it should be amenable to the production of larger quantities.",10.1021/acs.oprd.0c00009,2020-02-10,0.6319181921158755
Organic Letters,Highly Efficient and Diastereoselective Synthesis of (+)-Lineatin,[reaction: see text] A linear sequence was used to synthesize (+)-lineatin in 14 steps and 14% overall yield from a homochiral 2(5H)-furanone. Key steps of this synthetic approach feature the diastereoselective construction of a cyclobutene through a photochemical [2 + 2] cycloaddition and a regiocontrolled oxymercuration reaction.,10.1021/ol0497032,2004-04-01,0.6319056499367989
Journal of Organic Chemistry,Formal Total Synthesis of (+)-Neopeltolide,"This paper describes the formal total synthesis of (+)-neopeltolide, a cytotoxic macrolide isolated from the marine sponge Neopeltidae. The key features of the synthesis include an asymmetric Evans alkylation to fix the C9-methyl center, Jacobsen hydrolytic kinetic resolution of terminal epoxides followed by their regioselective opening to fix the stereocenters at the C11 and C13 positions, respectively, a Pd-catalyzed oxa-Michael reaction to construct the tetrahydropyran ring, and Yamaguchi macrolactonization to form the macrocyclic core of the molecule.",10.1021/jo301425c,2012-10-05,0.631900881473368
Synthesis,"The Use of 1,4-Dipolar Aryne Cycloaddition Strategy in Anthracyclinone Synthesis: The Formal Synthesis of (±)-4-Demethoxydaunomycinone","(opens in new window) Buy Article (opens in new window) Permissions and Reprints (opens in new window) All articles of this category (opens in new window) We report herein the convergent synthesis of the 7,8,9,10-tetrahydro-9-hydroxy-6,11-dimethoxy-5,12-naphthacenedione ( 9 ), an advanced intermediate in the synthesis of (±)-4-demethoxy-daunomycinone, using the aryne dipolar cycloaddition reaction of lithiated 3-cyanophthalide and 2-bromo-5,6-dihydro-1,4-dimethoxynapththalene ( 6 ) in the key step. Similarly, the non-convergent synthesis of the 7,8-dihydro-4,6,11-trimethoxy-5,12-naphthacenedione ( 10 ), an important intermediate in the synthesis of (±)-daunomycinone, is presented.",10.1055/s-1991-26373,1991-01-01,0.6318915650024889
Synlett,A Novel Approach to the Ergot Alkaloid Skeleton,"All articles of this category We describe a ten stage synthesis of an advanced intermediate for elaboration into ergot alkaloids, from 4-carbomethoxyindole. The key step involved an intramolecular cyclisation involving the allyl cation derived from N-benzenesulphonyl, 3-(3’-methoxyprop-2’-en-1’-yl), 4-(1’-hydroxy-2’-trimethylsilylmethyl-prop-2’-en-1’-yl)-indole. intramolecular [3+2] cycloaddition - allyl cation",10.1055/s-1995-4869,1995-01-01,0.6318894664000099
Organic Letters,Concise Total Synthesis of (±)-Pseudotabersonine via Double Ring-Closing Metathesis Strategy,"A concise synthesis of (+/-)-pseudotabersonine from commercially available 1-(phenylsulfonyl)-3-indolecarboxaldehyde has been accomplished. This synthesis features the convergent assembly of a key intermediate via a stepwise variant of a Mannich-type multicomponent coupling process, a double ring-closing metathesis, and a one-pot deprotection/cyclization reaction.",10.1021/ol101356u,2010-07-19,0.63187931305468
Journal of Organic Chemistry,Concise Total Synthesis of (−)-Deoxocuscohygrine and (−)-Dihydrocuscohygrine,"The concise enantioselective total synthesis of C(2)-asymmetrical (-)-deoxocuscohygrine and (-)-dihydrocuscohygrine are described. Double-diastereoselective additions of normal Grignard reagent to bis(1,3-oxazolidine) have been deployed to construct chiral diamine fragments as a key step.",10.1021/jo801700f,2008-10-29,0.6318731103183892
Organic Letters,Efficient Synthesis of 2-(Trifluoromethyl)nicotinic Acid Derivatives from Simple Fluorinated Precursors,"Novel routes to 2-trifluoromethyl-nicotinic acid derivatives have been developed involving synthesis of the pyridine ring. These pyridyl compounds serve as key intermediates in the manufacture of the recently discovered COMT inhibitor, 3-(5-(3,4-dihydroxy-5-nitrophenyl)-1,2,4-oxadiazol-3-yl)-2-(trifluoromethyl)pyridine 1-oxide.",10.1021/ol800458k,2008-04-10,0.6318726374565197
European Journal of Organic Chemistry,Formal Synthesis of (–)‐Perhydrohistrionicotoxin Using a Thorpe‐Ziegler Cyclization Approach. Synthesis of Functionalized Aza‐Spirocycles,"The formal synthesis of (–)‐PHTX is described. Our approach was based on the anodic cyanation of ( S )‐1‐(1‐phenylethyl)‐piperidine (–)‐ 1 to afford α‐aminonitrile 2 in 85 % yield in a 53:47 dr . The presence of the α‐phenylethyl group as the chiral auxiliary ensured the control of the absolute configuration of the future C6 spiro‐center during the alkylation step of 2 , which was carried out with 1‐bromo‐4‐chlorobutane. Next, elaboration of the 1‐azaspiro[5,5]undecane‐7‐one ring system was achieved in a two‐step sequence, involving (a) a Thorpe‐Ziegler annulation, and (b) the hydrolysis–decarboxylation of enaminonitrile (–)‐ 5 to afford spiroketone (+)‐ 6 in &gt;99:1 dr . Finally, the incorporation of the future C7 butyl chain was carried out stereoselectively through a new reaction sequence which involved the synthesis of tricyclic oxazolidinone (–)‐ 11 and alkylation of the intermediary syn ‐fluorohydrin (+)‐ 13 with n BuMgCl to form oxazolidinone (+)‐ 15 in an overall 19 % yield from (–)‐ 1 .",10.1002/ejoc.201801604,2018-11-16,0.6318704465663003
Journal of the American Chemical Society,Total Synthesis of Enlicitide Decanoate,"We report the total synthesis of enlicitide decanoate, an orally bioavailable inhibitor of proprotein convertase subtilisin/kexin type 9 that is being developed for the treatment of atherosclerotic cardiovascular disease. It is a highly complex macrocyclic peptide with a significant number of nonpeptide structural elements that presents a daunting synthetic chemistry challenge. We describe the development of a convergent, efficient, and robust manufacturing process that enables the large-scale production of enlicitide.",10.1021/jacs.4c15966,2025-03-24,0.6318349288559024
Journal of Organic Chemistry,Enantioselective Total Synthesis of Spirotryprostatin A,"In this paper, we disclosed a novel enantioselective total synthesis of spirotryprostatin A ( 1 ) in 15 steps with a 7.4% total yield from commercially available 2-iodo-5-methoxyaniline and γ-butyrolactone. The key step features of this synthesis include the copper-catalyzed cascade reaction of o -iodoaniline derivatives with alkynone to introduce the quaternary carbon stereocenter and an aza-Michael tandem reaction to construct the spiro[pyrrolidine-3,3′-oxindole] moiety.",10.1021/acs.joc.2c02391,2022-11-29,0.63183156190794
Journal of Organic Chemistry,"Synthesis of ABBV-168, a 2′-Bromouridine for the Treatment of Hepatitis C","ABBV-168 is a dihalogenated nucleotide under investigation for the treatment of hepatitis C virus. Three synthetic routes aimed at achieving the stereoselective installation of the C2' gem-Br,F substitution and subsequent Vorbruggen glycosylation were explored to prepare the penultimate nucleoside intermediate. Development culminated in a route to ABBV-168 featuring a de novo chromatography-free furanose synthesis, protecting group-directed Vorbruggen glycosylation, and highly selective phosphoramidation to furnish the API.",10.1021/acs.joc.8b02341,2018-11-09,0.6318123355191398
Organic Process Research & Development,Glucokinase Activator: Practical Asymmetric Hydrogenation and Scalable Synthesis of an API Fragment,"The enantioselective synthesis of ( R )-2-(3-chloro-4-methanesulfonyl-phenyl)-3-cyclopentyl propionic acid ( R )- 2 is described. The key intermediate ( E )- 7, a trisubstituted α-aryl β-alkyl acrylic acid, was conveniently accessed as its dicyclohexylamine salt by Perkin reaction in good yield and purity. Subsequent asymmetric hydrogenation with ruthenium catalysts was achieved with complete conversion and catalyst loadings up to S / C 75000 and enantiomeric excess up to 99% after crystallization.",10.1021/op4002164,2013-10-09,0.6317920844116068
Organic Letters,Efficient and Scalable Enantioselective Synthesis of a CGRP Antagonist,"An enantioselective synthesis of the CGRP antagonist BMS-846372, amenable to large scale preparation, is presented. This new synthesis showcases a chemo- and enantioselective reduction of a cyclohepta[b]pyridine-5,9-dione as well as a Pd-catalyzed alpha-arylation reaction to form the key carbon-carbon bond and set the absolute and relative stereochemistry.",10.1021/ol302262q,2012-09-06,0.6317828498803101
Synlett,Enantioselective Total Synthesis of (-)-<i>trans</i>-Dendrochrysine via a Ring-Rearrangement Metathesis Approach,The enantioselective total synthesis of the dipyrrolidine alkaloid (-)-trans-dendrochrysine was accomplished in 18 steps starting from tropone. The key step was a ring-rearrangement ­metathesis for the construction of the bisheterocyclic skeleton of the natural product in a single step.,10.1055/s-2007-986672,2007-09-21,0.6317815232399999
European Journal of Organic Chemistry,A Concise and Efficient Synthesis of [2-Methyl-5-methylsulfonyl-4-(pyrrol-1-yl)benzoyl]guanidinium Methanesulfonate (Eniporide),"A new synthesis of the benzoylguanidine-type Na+/H+ antiporter inhibitor eniporide (7) is described. Starting from 2-bromo-5-fluorotoluene (1), aromatic substituents were introduced by methanesulfonylation, Pd-catalyzed carboxylation with CO, and halogen−pyrrole exchange. Guanidine acylation was performed using Mukaiyama’s procedure.",10.1002/1099-0690(200006)2000:12<2253::aid-ejoc2253>3.0.co;2-q,2000-06-01,0.6317730382632869
Journal of Organic Chemistry,"Linear Total Synthetic Routes to β-<scp>d</scp>-<i>C</i>-(1,6)-Linked Oligoglucoses and Oligogalactoses up to Pentaoses by Iterative Wittig Olefination Assembly","Two complementary routes, A and B, have been followed for the stepwise iterative assembly of beta-D-(1,6)-glucopyranose and galactopyranose residues through methylene bridges. In route A the building block was constituted by 2,3,4-tri-O-benzyl-6-O-tert-butyldiphenylsilyl (O-TBDPS) beta-linked galactosylmethylenephosphorane, while in route B the building block was a beta-linked formyl C-glycopyranoside with a similar orthogonal protection of hydroxy groups. In route A each cycle consisted of the reaction of the phosphorane building block with a sugar residue bearing a formyl group at the C-5 carbon atom (coupling) and transformation of the O-TBDPS-protected primary alcohol into the formyl group (arming). Accordingly, route A is defined as the aldehyde route. On the other hand, each cycle in route B involved the coupling of the sugar aldehyde building block with a substrate bearing a phosphorus ylide at C-6 and introduction of the phosphonium group in the arming step as a precursor of the ylide functionality. Accordingly, route B is defined as the ylide route. The efficiency of route A proved to be seriously hampered by the 1,2-elimination of BnOH under the basic reaction conditions of the Wittig olefination, giving rise to the formation of substantial amounts of enopyranose. On the other hand, the ylide route B proved to be more efficient since very good yields (70-93%) of the isolated Wittig products were obtained throughout four consecutive cycles. Individual olefins and polyolefins obtained by routes A and B using gluco and galacto substrates were reduced and debenzylated in one pot by H(2)/Pd(OH)(2) to give the corresponding beta-D-C-(1,6)-linked oligosaccharides up to the pentaose stage. The latter compounds were fully characterized by high-field NMR spectroscopy (500 MHz).",10.1021/jo011142u,2002-05-17,0.6317519106120787
European Journal of Organic Chemistry,"A Practical and Efficient Total Synthesis of Potent Insulinotropic (2<i>S</i>,3<i>R</i>,4<i>S</i>)‐4‐Hydroxyisoleucine through a Chiral <i>N</i>‐Protected γ‐Keto‐α‐aminoester","Abstract (2 S ,3 R ,4 S )‐4‐Hydroxyisoleucine, which exhibits remarkable insulinotropic activity, is expected to be a potent drug to treat type II diabetes. We propose herein a four‐step synthesis of the enantiopure natural product on the basis of successive Mannich condensation, catalytic epimerization, N ‐ para ‐methoxyphenyl deprotection, and diastereoselective reduction. This compact economical and scalable sequence enables to perfectly control three contiguous chiral centers. It does not involve any chromatographic purification, and the desired compound is obtained in &gt;99 % de , &gt;99 % ee , and 22 % overall yield under our optimized conditions.",10.1002/ejoc.201000378,2010-06-14,0.6317216942894774
Organic Process Research & Development,"Development of a Scalable Process for 1-(3,5-Dichlorophenyl)-5-iodo-3-methyl- (4-methylbenzyl)-1<i>H</i>-imidazo[1,2-<i>a</i>]imidazol-2-one:  A Key Intermediate for the Synthesis of LFA-1 Inhibitors","A safe, robust, chromatography-free and reproducible process for the multi-kilogram synthesis of vinyl iodide 2, a key intermediate for the synthesis of LFA-1 inhibitors, was developed and implemented at the pilot plant. Execution of the above process allowed us to support preclinical activities in the LFA-1 program.",10.1021/op049813o,2005-01-15,0.6317124790828947
Journal of the American Chemical Society,Unified Total Synthesis of Phrymarolin and Haedoxan Natural Products,"High Resolution Image Download MS PowerPoint Slide We disclose a unified synthetic route to the furofuran lignans phrymarolin I and II as well as the insecticidal natural products haedoxan A and D. The furofuran core was constructed using a formal [3 + 2] cycloaddition between an α-silyloxy aldehyde and a styrene, followed by a samarium(II) iodide promoted-cyclization of a β-formyloxy ketone. While this sequence enabled the synthesis of phrymarolin I and II in eight steps, attempts to unmask the ortho -quinone necessary for a bioinspired formal [4 + 2] cycloaddition were unsuccessful, initially preventing access to the haedoxans. Revising the choice of the arene substitution pattern enabled the formation of the requisite ortho -quinone followed by a bioinspired cyclization to the 1,4-benzodioxane motif of the haedoxan framework. Finally, late-stage diversification at the acetal position enabled completion of the synthesis of haedoxan A and D and their analogues in 13 steps. The synthetic route facilitated insecticidal screening of fully synthetic analogues modified at the O -aryl residue.",10.1021/jacs.5c16676,2025-12-04,0.6317100687098078
Journal of Organic Chemistry,Flexible Synthesis and Biological Activity of Uronic Acid-Type <i>gem</i>-Diamine 1-<i>N</i>-Iminosugars:  A New Family of Glycosidase Inhibitors,"An efficient and flexible synthetic route to four gem-diamine 1-N-iminosugars of uronic acid-type (D-glucuronic, D-mannuronic, L-iduronic, and L-guluronic acid), a new family of glycosidase inhibitor, from l-galactono-1,4-lactone have been developed in an enantiodivergent fashion through a sequence involving as the key steps (a) the formation of gem-diamine 1-N-iminopyranose ring by the Mitsunobu reaction of an aminal and (b) the introduction of a carboxylic acid group by the Wittig reaction of a ketone, hydroboration and oxidation, and the Sharpless oxidation. D-Glucuronic and D-mannuronic acid-type 1-N-iminosugars, (3S,4R,5R, 6R)- and (3S,4R,5R,6S)-4, 5-dihydroxy-6-trifluoroacetamido-3-piperidinecarboxylic acid, were proven to be potent inhibitors for beta-D-glucuronidase (IC(50) 6.5 x 10(-)(8)M) and to affect human heparanase (endo-beta-glucuronidase).",10.1021/jo982448c,1999-12-17,0.6316773812125086
Organic Letters,Toward the Total Synthesis of Amphidinolide N: Synthesis of the C8–C29 Fragment,"A synthesis of the C8-C29 fragment of amphidinolide N, a potent cytotoxic macrolide isolated from the marine dinoflagellate Amphidinium sp., has been achieved. The key features of the synthesis involve a convergent union of the C9-C15 and C16-C29 fragments by Steglich esterification and the construction of a pyran unit through a Tebbe methylenation/ring-closing metathesis sequence.",10.1021/acs.orglett.6b00871,2016-04-26,0.6316740238240541
Journal of Organic Chemistry,"Bioinspired Syntheses of the Pyridoacridine Marine Alkaloids Demethyldeoxyamphimedine, Deoxyamphimedine, and Amphimedine","Efficient bioinspired syntheses of the biologically active pyridoacridine marine alkaloids demethyldeoxyamphimedine, deoxyamphimedine, and amphimedine are reported. Reaction of styelsamine D, prepared via an optimized route starting from Boc-dopamine, with paraformaldehyde afforded demethyldeoxyamphimedine and deoxyamphimedine. Oxidation of the latter using either K3[Fe(CN)6] or DMSO/conc. HCl gave amphimedine in 8 steps from tryptamine with an overall yield of 14%. The versatility of the method was demonstrated by the synthesis of non-natural ethyl and benzyl congeners of deoxyamphimedine and amphimedine.",10.1021/acs.joc.5b02312,2015-12-07,0.6316731583622373
Synlett,Total Synthesis of Danshenspiroketallactone,"Described herein is the first synthesis of the monobenz­annulated 5,5-spiroketals danshenspiroketallactone and epi-danshen­spiroketallactone, two components of the traditional Chinese medicine Danshen. Key features of the synthesis include a directed metallation-lactonisation sequence to install the isobenzofuranone moiety and an oxidative radical cyclisation to afford the monobenz­annulated 5,5-spiroketal.",10.1055/s-0031-1290082,2011-11-28,0.6316668202208712
Tetrahedron,Photolactamization: A Novel Synthetic Entry into Large Ring-Sized Lactams,,10.1016/0040-4039(92)88118-o,1992-04-01,0.6316612869995119
Journal of Organic Chemistry,Total Synthesis of Microcarpalide,"[reaction: see text] An efficient, convergent approach for the total synthesis of microcarpalide (1) is described. The synthetic strategy features the Sharpless asymmetric dihydroxylation, regioselective epoxide opening with various nucleophiles such as a lithium acetylide and cuprates derived from the vinyl stannane and the vinyl iodide for the construction of a C7-C8 trans-double bond and Yamaguchi macrolactonization as the key steps.",10.1021/jo050193e,2005-04-12,0.6316447118522319
Organic Letters,Total Synthesis of Anachelin H,"[structure: see text] The first total synthesis of anachelin H is reported. Starting from L-Ser, a stereodivergent synthesis of the polyketide fragment resulting in all possible diastereoisomers is described. The alkaloid peptide fragment is prepared via a tellurium-mediated oxidative aza annulation as the key step. Coupling of the fragments gave synthetic anachelin H, which was found to be identical to a sample of the natural product, thus confirming the configuration by total synthesis.",10.1021/ol048068x,2004-11-13,0.6316441705054003
Synthesis,"Efficient Synthesis of 3,7-Diaryl-1,4-dihydro[1,2,4]triazolo[5,1-c][1,2,4]triazines","An efficient and versatile protocol for the synthesis of novel 3,7-diaryl-substituted 1,4-dihydro[1,2,4]triazolo[5,1- c ][1,2,4]triazines is described, via alkylation/cyclization of 3,5-dibromo-1 H -1,2,4-triazole, followed by Suzuki coupling with arylboronic acids.",10.1055/s-0032-1317021,2012-08-15,0.6316341777174816
Tetrahedron,An improved and efficient synthesis of pinene based bipyridyldiols and bipyridine,,10.1016/j.tetlet.2016.03.075,2016-03-23,0.6316265091308011
Synthesis,Total Synthesis of Cryptopleurine and Its Analogues,Abstract Total synthesis of phenanthroquinolizidine alkaloid cryptopleurine was achieved in 8 steps from commercially available 2-pyridinecarboxaldehyde and the epoxide derived from methyleugenol. The key intermediate vinyl triflate enables the divergent synthesis of crypto­pleurine derivatives by late-stage installation of various substituents on the C-ring.,10.1055/a-1730-8628,2022-01-04,0.6316198231176946
Angewandte Chemie International Edition,Total Synthesis of Bryostatin 3,"A convergent synthetic strategy has been used to accomplish the first total synthesis of the title compound 1, a γ-lactone-containing member of the antineoplastic marine macrolide family. The C1−C16 and C17−C27 fragments were combined by the Julia–Lythgoe olefination and the Yamaguchi macrolactonization. This was followed by the stereoselective introduction of a methoxycarbonylmethylene group, and final hydrolysis of the acetal provided access to the target molecule 1.",10.1002/1521-3773(20000703)39:13<2290::aid-anie2290>3.0.co;2-6,2000-07-03,0.6316139447516337
Journal of the American Chemical Society,Total Synthesis of (+)-Pinnatoxin A,A convergent enantioselective total synthesis of (+)-pinnatoxin A is described. The synthesis capitalizes on the highly diastereoselective Ireland-Claisen rearrangement of an acyclic alpha-branched allylic ester to set the quaternary stereogenic center at the core of the spiroimine ring system along with the adjacent tertiary stereocenter. The all-carbon macrocyclic ring system was formed by ring-closing metathesis.,10.1021/ja800435j,2008-03-01,0.6316043700501427
Journal of the American Chemical Society,Total Syntheses of (+)- and (−)-Cacospongionolide B:  New Insight into Structural Requirements for Phospholipase A<sub>2</sub> Inhibition,The first total synthesis of the antiinflammatory marine sponge metabolite (+)-cacospongionolide B has been accomplished in 12 linear steps. The pivotal transformations include a three-step sequence coupling the two main regions of the natural product as well as generating the side chain dihydropyran ring. The activity of the synthetic analogues against bee venom phospholipase A(2) suggests that cacospongionolide B has an enantiospecific interaction with the enzyme that is independent of the gamma-hydroxybutenolide moiety.,10.1021/ja026899x,2002-09-06,0.6316026314602217
Organic Letters,Progress toward the De Novo Asymmetric Synthesis of Euphanes,"Progress toward an asymmetric synthesis of euphanes is described. A C14-desmethyl euphane system possessing five differentially substituted and electronically distinct alkenes has been prepared. The route employed is based on sequential metallacycle-mediated annulative cross-coupling, double asymmetric Brønsted acid mediated intramolecular Friedel-Crafts alkylation, and an oxidative rearrangement to establish the requisite C10 quaternary center. These studies have also led to the discovery of a novel euphane-based modulator of the Liver X Receptor.",10.1021/acs.orglett.2c01299,2022-05-18,0.6315575716958587
Tetrahedron,Synthesis of cryptoporic acid A methyl ester,,10.1016/s0040-4039(00)00317-8,2000-04-01,0.6315328849061437
Tetrahedron,A stereocontrolled synthesis of the methyl ester of (±)-nonactic acid,,10.1016/s0040-4039(00)77765-3,1980-01-01,0.6315328849061437
Tetrahedron,An efficient synthesis of a novel bifunctional chelating agent,,10.1016/s0040-4039(98)02008-5,1998-12-01,0.631532440473953
Tetrahedron,A two step biomimetic total synthesis of eilatin,,10.1016/s0040-4039(00)60790-6,1993-03-01,0.6315101487521979
Synthesis,A Facile Synthesis of (4S)-4-[(1R)-1-Carboxyethyl]-1-(tert-butyldimenthylsilyl)azetidin-2-one: A Key Intermediate of 1-β-Methylcarbapenems,"All articles of this category Titanium enolate-mediated aldol-type reaction of the chiral N -propionyl-1,3-benzoxyzinone 4 with 4-acetoxyazetidin-2-one (5) gave the 2-(2-oxoazetidin-4-yl)propionic acid derivative 6 in high yield with high selectivity, which was transformed into (4 S )-4-[(1 R )-1-carboxyethyl]-1-( tert -butyldimethylsilyl)azetidin-2-one (3) , a key intermediate of 1- β -methylcarbapenems 1 . A 1- β -methylcarbapenem key intermediate was conveniently prepared by the aldol-type reaction of chiral N -propionyl-1,3-benzoxazinone with 4-acetoxyazetidin-2-one",10.1055/s-1997-1502,1997-01-01,0.6315078997606678
Tetrahedron,"Preparation of a 1,2-isoxazolidine synthon for the synthesis of zetekitoxin AB",,10.1016/j.tetlet.2015.09.070,2015-09-21,0.6314602251395667
Tetrahedron,Synthesis of stereospecifically labeled carbohydrates: Preparation of (3S)− and (3R)-[3-2H1]ascarylose,,10.1016/s0040-4039(00)95914-8,1987-01-01,0.6314602251395667
Tetrahedron,Furans in Synthesis. The Preparation of (±)-Lactaral,,10.1016/s0040-4039(00)85880-3,1982-01-01,0.6314602251395667
Tetrahedron,"Synthesis of dihydrofurans from diazomethane and phenolic mannich methiodides preparation of 3-demethoxy-4′, 5′-dihydrofuro[2′,3′:3,4]thiocolchicine",,10.1016/s0040-4039(01)88466-5,1969-01-01,0.6314602251395667
Tetrahedron,Synthesis of stereospecifically labeled carbohydrates II1: preparation of (3S)- and (3R)-[3-2H1]abequose,,10.1016/s0040-4039(00)80459-1,1988-01-01,0.6314602251395667
Tetrahedron,Synthesis of fluorinated drimanes. Preparation of 9αF-drimenin,,10.1016/s0040-4039(03)00076-5,2003-02-01,0.6314602251395667
Tetrahedron,Cyclopalladated imines in synthesis: the preparation of unsymmetrical stilbenes and 3-arylisoquinolones,,10.1016/s0040-4039(00)87233-0,1982-01-01,0.6314602251395667
Organic Letters,Total Synthesis of the Hallucinogenic Neoclerodane Diterpenoid Salvinorin A,"Total synthesis of salvinorin A (1), a neoclerodane diterpenoid having the most potent hallucinogenic activity and a selective kappa-opioid agonist, was completed in 20 steps starting from enantiomerically pure hydroxy-Wieland-Miescher ketone 5.",10.1021/ol800101v,2008-03-01,0.6314581201923446
Organic Letters,"Asymmetric Synthesis of <i>trans</i>-3,4-Dialkyl-γ-butyrolactones via an Acyl-Claisen and Iodolactonization Route","[reaction: see text] A new, efficient, and general asymmetric synthesis of enantiomerically pure trans-3,4-dialkyl-gamma-lactones has been developed. The key steps are (1) copper-catalyzed three-component coupling of chiral amine, aldehyde, and alkyne, (2) acyl-Claisen rearrangement, and (3) iodolactonization. The products, chiral gamma-lactones, are versatile synthetic intermediates and structural units of natural products and modified nucleosides.",10.1021/ol050578j,2005-06-16,0.6314521276227492
Organic Letters,Enantioselective Synthesis of (−)-Roccellaric Acid,"[reaction in text] A new strategy for the synthesis of anti-4,5-disubstituted gamma-butyrolactones starting from inexpensive furan-2-carboxylic methyl ester was developed. By applying this methodology, the enantioselective synthesis of (-)-roccellaric acid ((-)-17) was accomplished using a copper(I)-catalyzed asymmetric cyclopropanation, a tin(IV)-catalyzed retroaldol/lactonization sequence of cyclopropanols, and a ruthenium-catalyzed intermolecular metathesis reaction as key steps.",10.1021/ol015686u,2001-04-04,0.631451106472245
Journal of Organic Chemistry,"An Efficient, PIFA Mediated Approach to Benzo-, Naphtho-, and Heterocycle-Fused Pyrrolo[2,1-<i>c</i>][1,4]diazepines. An Advantageous Access to the Antitumor Antibiotic DC-81","[reaction: see text] The synthesis of a series of optically pure benzo-, naphtho-, and heterocycle-fused pyrrolo[2,1-c][1,4]-diazepin-5,11-dione derivatives starting from l-proline methyl ester is presented. The synthetic plan includes an aroylation step at the proline nitrogen followed by transformation of the ester residue into a N-methoxyamide group. The subsequent key cyclization step embraces the PIFA mediated formation of a N-acylnitrenium intermediate and its succeeding intramolecular trapping by the aromatic ring. The presented general approach solves the need of starting from not very accessible amino (or a related functionality) aromatic starting materials, and its effectiveness is demonstrated in the synthesis of the antitumor antibiotic DC-81.",10.1021/jo047872u,2005-02-17,0.6314501456932214
Tetrahedron,AuBr3-catalyzed cyclization of o-(alkynyl)nitrobenzenes. Efficient synthesis of isatogens and anthranils,,10.1016/s0040-4039(03)01357-1,2003-07-01,0.6314451279606371
Tetrahedron,An efficient synthesis of indoles via a CuMgAl-LDH-catalyzed cyclization of 2-alkynylsulfonanilides,,10.1016/j.tetlet.2018.09.009,2018-09-05,0.6314451279606371
Tetrahedron,Synthesis of a new prostaglandin endoperoxide (PGH2) analog and its function as an inhibitor of the biosynthesis of thromboxane A2 (TBXA2),,10.1016/s0040-4039(01)93541-5,1979-01-01,0.6314196396237042
Journal of Organic Chemistry,Synthesis and Biological Evaluation of (±)-Dinemasone C and Analogues,"Dinemasone C was prepared in three steps (8% overall yield) from cis-tetrahydro-4-hydroxy-6-methyl-2-pyrone by aldol reaction with 2,4-hexadienal, epoxidation followed by cyclization, and epimerization of the ring fusion. Dinemasone C, epi-dinemasone C, anhydrodinemasone BC, and nor-dinemasone B are active against bacteria, including Legionella pneumophila Corby, algae, and fungi.",10.1021/jo101408s,2010-08-04,0.6314171820750026
Synthesis,"A New Route to 1,4-Dihydro-1,2,4,5-tetrazines via Stabilized Sulfuranes",,10.1055/s-1983-30332,1983-01-01,0.6313884086443674
Organic Letters,Intramolecular Cyclopropene-Furan [2 + 4] Cycloaddition followed by a Cyclopropylcarbinyl Rearrangement to Synthesize the BCD Rings of Cortistatin A,"Synthesis of the BCD ring system of cortistatin A has been accomplished in 9 steps and 30% overall yield starting from commercially available 2-methylcyclopent-2-enone. Key transformations include the addition of cyclopropenyllithium 16 to aldehyde 15, an intramolecular cyclopropene-furan [2 + 4] cycloaddition leading to epimers 18/19, and a subsequent cyclopropylcarbinyl rearrangement to afford 24.",10.1021/ol901537n,2009-08-05,0.6313750882123293
Journal of the American Chemical Society,Total Synthesis of (−)-Apicularen A,Complete details of an asymmetric synthesis of apicularen (1) are described. The synthesis has been accomplished using a highly diastereo- and enantioselective [4 + 2] annulation for the assembly of the functionalized pyran core. An underdeveloped lactonization method involving an NaH promoted transesterification of an advanced intermediate bearing an aryl cyanomethyl ester was used for the macrolactonization step.,10.1021/ja037957x,2004-02-04,0.6313420175308595
Organic Letters,Short Enantioselective Total Synthesis of (−)-Rhazinilam Using a Gold(I)-Catalyzed Cyclization,(R)-(-)-Rhazinilam has been synthesized in nine steps and 20% overall yield. The key steps involve two metal-catalyzed processes: the enantioselective gold(I)-catalyzed cycloisomerization of an allene-functionalized pyrrole and the palladium-catalyzed hydrocarboxylation of a vinyl moiety with formate as a CO surrogate. This novel strategy represents the shortest and highest yielding enantioselective total synthesis of (-)-rhazinilam.,10.1021/acs.orglett.7b02210,2017-09-06,0.6313352199811422
Synthesis,"Synthesis of Novel Octahedral Silicon Compounds; Synthesis of Bis[3-(1-{[aryl(hydroxy)methylene]hydrazinylidene}ethyl)-6-methyl-2-oxo-2H-pyran-4-olato-N,O,O′]silicon(IV)",The synthesis of new silicon compounds is reported via the cyclization of dehydroacetic acid N -acylhydrazones with silicon tetraacetate. The procedure involves formation of new octahedral hexacoordinated silicon structures.,10.1055/s-0033-1338924,2013-06-24,0.63132663171782
Journal of the American Chemical Society,Concise Total Synthesis of (+)-Lyconadin A,"The total synthesis of lyconadin A from (R)-5-methylcyclohex-2-enone was accomplished. Our synthesis features the facile construction of a highly fused tetracyclic compound through a combination of an aza-Prins reaction and an electrocyclic ring opening. Transformation of the bromoalkene moiety in the tetracycle could be achieved by either a vinylogous Pummerer rearrangement or the formation and subsequent isomerization of the nitrosoalkene to furnish an α,β-unsaturated ketone, from which the pyridone ring was constructed.",10.1021/ja109516f,2010-12-14,0.6313262265414499
Synthesis,Chemoenzymatic Synthesis of (<i>R</i>)-(-)-Citramalic Acid,"All articles of this category Dimethyl ( R )-(-)-citramalate (dimethyl 2-hydroxy-2-methylsuccinate, 4 ) was prepared in ≍ 50% overall yield in four steps from ethyl chloro(hydroxyimino)acetate and ethyl methacrylate. The key transformation involved a regio- and enantiospecific hydrolysis of diethyl ( RS )-5-methyl-4, 5-dihydroisoxazole-3,5-dicarboxylate (1a) using a protease from Aspergillus oryzae .",10.1055/s-1992-26110,1992-01-01,0.6312848866291197
Organic Letters,Stereocontrolled Synthesis of Arylomycin-Based Gram-Negative Antibiotic GDC-5338,"We report herein an efficient, stereocontrolled, and chromatography-free synthesis of the novel broad spectrum antibiotic GDC-5338 . The route features the construction of a functionalized tripeptide backbone, a high-yielding macrocyclization via a Pd-catalyzed Suzuki–Miyaura reaction, and the late-stage elaboration of key amide bonds with minimal stereochemical erosion. Through extensive reaction development and analytical understanding, these key advancements allowed the preparation of GDC-5338 in 17 steps, 15% overall yield, >99 A % HPLC, and >99:1 dr.",10.1021/acs.orglett.9b03481,2019-10-31,0.6312784321959745
Organic Process Research & Development,"The Expedient Synthesis of 4,2‘-Difluoro-5‘-(7-trifluoromethyl- imidazo[1,2<i>-a</i>]pyrimidin-3-yl)biphenyl-2-carbonitrile, a GABA α2/3 Agonist","An expedient regioselective synthesis of a GABA α2/3 agonist 1 is described . The key step is an efficient regioselective palladium-catalyzed coupling of 7-trifluoromethylimidazo[1,2- a ]pyrimidine ( 5 ) to 5‘-chloro-4,2‘-difluorobiphenyl-2-carbonitrile ( 15 ). The efficiency of this step was affected by the choice of solvent, ligand, and tetrabutylammonium salt additive.",10.1021/op050217j,2006-03-17,0.6312752755722253
Organic Letters,Total Synthesis of Chaetominine,"An efficient, asymmetric synthesis of the cytotoxic natural product chaetominine was achieved in 14 steps. The strategy employs a copper(I)-mediated cyclization reaction as a key step to install the abc-tricyclic ring system, which was further elaborated by diastereoselective oxidation and reduction reactions. This effort also documents the first example of an oxidative rearrangement yielding to homochiral spirocyclic pyrrolidinyloxindoles.",10.1021/ol802155n,2008-10-11,0.6312744280499382
Journal of the American Chemical Society,Total Synthesis of Absinthin,"(+)-Absinthin, a structurally unique triterpene, has been efficiently constructed in nine reaction steps and in 18.6% overall yield from O-acetylisophotosantonic lactone. The synthesis features Mitsunobu arylselenylation, oxidative elimination of allylic arylselenides, biomimetic dimerization via regio- and stereospecific Diels-Alder reaction, and a four-step stereochemical inversion of a highly sterically congested tertiary alcohol. This approach has not only tackled the formidable synthetic challenges in assembling structurally complex (+)-absinthin but also paved an efficient synthetic route to a series of medicinally attractive absinthin analogues.",10.1021/ja0439219,2004-12-10,0.6312621578386264
Tetrahedron,"A route to Prelog-Djerassi lactone from methyl α,D-glucopyranoside",,10.1016/s0040-4039(01)90512-x,1981-01-01,0.6312620934897408
Journal of Organic Chemistry,"Organocatalytic, Enantioselective Synthesis of 1- and 3-Substituted Isochromans via Intramolecular Oxa-Michael Reaction of Alkoxyboronate: Synthesis of (+)-Sonepiprazole","The enantioselective oxa-Michael reaction of alkoxyboronate strategy was demonstrated to provide a new and practical route to enantioriched 1- and 3-substituted isochromans using a chiral bifunctional organocatalyst. Furthermore, this methodology was extended to the enantioselective synthesis of (+)-sonepiprazole, a dopamine receptor antagonist.",10.1021/acs.joc.5b00719,2015-06-23,0.6312575557572173
European Journal of Organic Chemistry,"A Practical Synthesis of 14-epi-19-nor-1α,25-Dihydroxyvitamin D3 Analogues and Their A-ring Epimers","A practical synthesis of (2S,3aS,4aS)-2-tert-butyldimethylsilyloxybicyclo[3.1.0]hexane-3a-carbaldehyde (14a) and diastereoisomers, starting from all-cis methyl 3,5-dihydroxy-1cyclohexanecarboxylate (24) is described. Coupling with appropriate cis-hydrindanes produces the title compounds. TX 522, a member of this series, is currently in phase II clinical studies for the treatment of psoriasis. The key step involves the coupling of 14 and 16 with the respective cis-hydrindanes 9 and 7.",10.1002/1099-0690(200110)2001:20<3779::aid-ejoc3779>3.0.co;2-q,2001-10-01,0.6312570437601132
Organic Letters,A Formal Synthesis of the Callipeltoside Aglycone,"A synthesis of the macrocyclic core structure of callipeltoside A and a C9 epimer has been achieved by applications of chiral vinylzinc or Kishi-Nozaki-Hiyama (K-N-H) additions, Roskamp homologations, and acylketene or intramolecular K-N-H macrolactonizations as key bond-forming steps.",10.1021/ol702024b,2007-12-05,0.6312442958306204
European Journal of Organic Chemistry,A Convergent Synthesis of Carbocyclic Sinefungin and its C‐5 Epimer,"Abstract A convergent synthesis of carbocyclic sinefungin ( 2 ), its C‐5 epimer 3a , and adenine‐modified derivative 3b is described. The key features of our approach include the use of commercially available L ‐methionine and readily available (1 R ,4 S )‐4‐hydroxy‐2‐cyclopentenyl acetate as starting materials, a cross‐metathesis reaction, an enzymatic kinetic resolution, and a Staudinger reduction. The current synthesis is flexible and, therefore, provides convenient access to the synthesis of various carbocyclic sinefungin analogues for biological evaluation.",10.1002/ejoc.201402812,2014-09-09,0.6312360690454755
Tetrahedron,Spiroacetal synthesis from a key lactone intermediate leading to novel C24 and C25-substituted milbemycins,,10.1016/0040-4039(94)85225-1,1994-04-01,0.631227040212948
Organic Letters,A Novel Stereocontrolled Approach to Eudesmanolides:  Total Synthesis of (±)-Gallicadiol and (±)-Isogallicadiol,"[reaction: see text] A novel approach for the stereocontrolled synthesis of eudesmanolides was developed based on a quasi-biomimetic strategy starting from a functionalized oxabicyclic template, as shown above, by which the first total syntheses of gallicadiol (6) and isogallicadiol (7) were achieved. The key elements of the synthesis include: (1) a facile and stereospecific synthesis of a functionalized epoxy aldehyde intermediate; (2) a mild Lewis acid-mediated stereoselective ene cyclization; and (3) a stereocontrolled gamma-lactonization.",10.1021/ol050850p,2005-06-15,0.6312248766598967
Journal of Organic Chemistry,<i>De Novo</i> Synthesis of the DEF-Ring Stereotriad Core of the <i>Veratrum</i> Alkaloids,"The synthesis of the stereotriad core in the eastern portion of the Veratrum alkaloids jervine ( 1 ), cyclopamine ( 2 ), and veratramine ( 3 ) is reported. Starting from a known β-methyltyrosine derivative ( 8 ), the route utilizes a diastereoselective substrate-controlled 1,2-reduction to establish the stereochemistry of the vicinal amino alcohol motif embedded within the targets. Oxidative dearomatization is demonstrated to be a viable approach for the synthesis of the spirocyclic DE ring junction found in jervine and cyclopamine.",10.1021/acs.joc.0c00685,2020-04-30,0.6312045821067802
Synthesis,"Synthesis of Enantiopure ω-(4-Fluorophenyl)-6,11-Methylene Lipoxin B4 Methyl Ester","Abstract The synthesis of Lipoxin B4 analogues (LXB4) to gain access to stabilized inflammation-resolving compounds is an active field of research. Focusing on variation and stabilization of the conjugated E,Z,E,E C6–C13 tetraene moiety of natural LXB4, a methylene bridge introduced between C6 and C11 suppresses any Z/E isomerization of the C8–C9 olefin. Furthermore, rapid ω-oxidation (C20) should be avoided by replacing the C18–C20 segment by an aromatic moiety. Optically active C1–C12 building blocks were accessed from methyl cycloheptatriene-1-carboxylate (C6–C11, C21) and glutaryl chloride (C1–C5) as described earlier. The ω-segment was generated via a five-step sequence starting from 4-arylbutanoic acid. Horner key olefination enabled assembly of the carbon backbone. A final five-step sequence including a chelate Cram reduction of the unsaturated ketone moiety afforded the target ω-aryl 6,11-methylene-LXB4 methyl ester.",10.1055/a-1512-1763,2021-05-19,0.6312023093049707
Journal of Organic Chemistry,Synthesis of the Tricyclic Core in Stemonamine Alkaloids via One-Pot Gold(I)-Catalyzed Cyclization and Schmidt Rearrangement: Formal Synthesis of (±)-Stemonamine,"An efficient synthesis of the tricyclic cyclopenta[1,2-b]pyrrolo[1,2-a]azepine nucleus of stemonamine alkaloids is reported. The key reaction utilizes a one-pot gold(I)-catalyzed cyclization and SnCl4-mediated Schmidt rearrangement. Notably, the phosphine ligand had a crucial effect on the gold(I)-catalyzed cyclization. As an application of this new methodology, the formal synthesis of (±)-stemonamine has been accomplished.",10.1021/jo502103p,2014-10-16,0.6311980732752105
Synthesis,Facile Synthesis of Uhle’s Ketone by the Regioselective Friedel-Crafts Cyclization,"All articles of this category A facile synthesis of Uhle’s ketone starting from 3-(indol-3-yl)propionic acid is described. In the presence of a large amount of donor-acceptor complex, the species generated from chloroacetyl chloride and aluminum chloride, 3-(1-trimethylacetylindol-3-yl)propionyl chloride reacts regioselectively to give trimethylacetyl derivative of Uhle’s ketone in 78% yield. Deacylation of trimethylacetyl group gives Uhle’s ketone in an overall yield of 67%. Efficient synthesis of Uhle’s ketone is described",10.1055/s-1995-3943,1995-05-01,0.631197525631334
Journal of Organic Chemistry,Synthesis of Tetrahydroisoquinoline Alkaloids via Anodic Cyanation as the Key Step,"We report a new route to tetrahydroisoquinoline (THIQ) alkaloids involving the alkylation of alpha-aminonitrile 2 as a key step. The latter compound was prepared by anodic cyanation of the corresponding tertiary amine 1. Reductive decyanation of alpha-aminonitriles 6a-c proceeded diastereoselectively (up to 95% de) to deliver the C1-substituted alkaloids precursors 9a-c. The syntheses of (+/-)-carnegine, (+/-)-norlaudanosine, and (+/-)-O,O-dimethylcoclaurine have been achieved.",10.1021/jo100714y,2010-07-21,0.6311959745157275
Journal of Organic Chemistry,"Total Synthesis of (−)-Herbindoles A, B, and C and (+)-<i>trans</i>-Herbindole A via a Convergent Benzannulation Strategy","The herbindoles are cyclopent[ g ]indole alkaloids whose structures incorporate a fully substituted benzenoid ring and, as such, have served as useful platforms for the testing and refinement of methods for the construction of highly substituted indoles. Herein we report efficient and convergent total syntheses of four herbindole alkaloids, including the first enantioselective total synthesis of trans -(+)-herbindole A. The pivotal step in the synthetic strategy is the application of our vinylketene-based benzannulation in which a thermal Wolff rearrangement generates a vinylketene which combines with an ynamide derivative in the first step of a pericyclic cascade that produces a highly substituted aniline intermediate primed for cyclization to form the cyclopent[ g ]indole ring system. Subsequent cross-coupling reactions allow for the elaboration of a common precursor to herbindoles of the A, B, and C series.",10.1021/acs.joc.5c00653,2025-05-14,0.6311953326323619
Synlett,A Stereocontrolled Entry to 3-Functionalized <i>cis</i>-3a-Methyloctahydroindoles: Building Blocks for <i>Daphniphyllum</i> Alkaloid Synthesis,"A synthetic entry to cis-3a-methyl-3-methyleneoctahydroindol-5-ones employing ozonolysis, chemoselective methylenation, and double reductive amination of 2-(1-formylvinyl)-2-methyl-1,4-cyclohexanedione monoethylene acetal is described. The same process using a 2-methoxycarbonyl derivative gave a trans-diastereoselectivity in the formation of the azabicyclic compound. Diastereoselective hydroboration of the exocyclic methylene of cis-octahydroindole derivative gives a valuable synthetic intermediate for Daphniphyllum alkaloid synthesis.",10.1055/s-2007-986633,2007-09-01,0.6311865413862234
Synlett,An Alternative Synthesis of a Potent GPIIb/IIIa Receptor Antagonist,All articles of this category A key intermediate to SB-214857 was prepared via an oxidative cyclization of a hydroquinone with a flanking aspartate side chain using Fremy's salt. benzodiazepine - cyclization - quinone - hydroquinone - oxidation,10.1055/s-1999-3094,1999-12-31,0.6311616835962787
European Journal of Organic Chemistry,"Total Synthesis of Bis(tetrahydroisoquinoline) Alkaloids: (−)‐Renieramycin M, (−)‐Renieramycin S, (−)‐Renieramycin T, (−)‐Jorumycin, (−)‐ Jorunnamycin A, and (−)‐Jorunnamycin C","A new approach to antitumor renieramycin‐type alkaloids is developed based on a regio‐ and stereoselective cyclization coupling of the phenolic aldehyde and amino alcohol partners, which both were obtained from commercial N ‐Cbz‐L‐tyrosine through a common synthetic process. The employment of Parikh−Doering oxidation with good functionality tolerance and successive biomimetic A‐ring modification facilitates the concise and universal approach, the utility of which is illustrated by the first synthesis of renieramycin S in 19 steps, as well as the collective syntheses of jorunnamycins A, C, jorumycin, renieramycins M, and T in 16–18 steps.",10.1002/ejoc.202501050,2025-12-29,0.6311521899310955
Organic Letters,Stereocontrolled Total Synthesis of (−)-Ebelactone A,"[structure: see text] The highly stereocontrolled hydroboration of an alkene, a subsequent Suzuki-Miyaura cross-coupling reaction, a silylcupration on a nonterminal acetylene, and an iododesilylation were the key steps in a convergent total synthesis of (-)-ebelactone A.",10.1021/ol020058d,2002-05-23,0.6311460728812386
Angewandte Chemie International Edition,Total Synthesis of Zoanthenol,"Reaching home plate: The first total synthesis of zoanthenol, an aromatic member of the zoanthamine alkaloid family with potent anti-platelet activity for human platelet aggregation, has been achieved using an intermediate in the total synthesis of norzoanthamine. The key step involves a Brønsted acid-promoted isoaromatization in the AB ring system to install the crucial aromatic ring.",10.1002/anie.200904537,2009-10-19,0.6311450425808854
Journal of Organic Chemistry,A Novel Formal Total Synthesis of Cephalotaxine,"A formal total synthesis of cephalotaxine (CET), the parent structure of antileukemia Cephalotaxus alkaloids, was achieved through a novel synthesis of the pentacyclic amino enone 4 by a rapid annulation of readily available beta-(3,4-methylenedioxy)phenethylamine (2), delta-valerolactone, and bromoacetone.",10.1021/jo048046o,2005-03-09,0.6311348401692962
Organic Letters,Catalytic Asymmetric Total Synthesis of Tangutorine,"The first enantioselective total synthesis of tangutorine has been achieved, wherein a Pd-catalyzed asymmetric allylic amination using a chiral diaminophosphine oxide (DIAPHOX) preligand was the key step.",10.1021/ol902929a,2010-01-21,0.6311264488726775
Angewandte Chemie International Edition,Isolation and Asymmetric Total Synthesis of Perforanoid A,"A novel limonoid, perforanoid A, was isolated, and an asymmetric total synthesis was achieved in 10 steps. The key steps are chiral tertiary aminonaphthol mediated enantioselective alkenylation of an aldehyde to an allylic alcohol, Pd-catalyzed coupling of the allylic alcohol with vinyl ether to form the γ-lactone ring, and cyclopentenone ring formation through a Rh-catalyzed Pauson-Khand reaction. Preliminary studies show that perforanoid A is cytotoxic towards HEL, K562, and CB3 tumor cell lines.",10.1002/anie.201602783,2016-05-11,0.6311250240190915
Synthesis,Asymmetric Synthesis of All Stereoisomers of α-Methylthreonine Using an Organocatalytic Steglich Rearrangement Reaction as a Key Step,An efficient synthetic route to all four stereoisomers of α-methylthreonine has been established. Each type of stereoisomer has been isolated in diastereomerically pure form and with an enantiomeric excess of at least 86% ee. The key step in this multi-step synthesis is an enantioselective organocatalytic Steglich rearrangement reaction of O-acetylated azlactones. The Steglich rearrangement was also extended to other substrates.,10.1055/s-0029-1217140,2009-11-20,0.6311204988520762
Organic Process Research & Development,Optimization and Scale-Up of the Grandberg Synthesis of 2-Methyltryptamine,"An efficient, safe, and cost-effective synthesis of 2-methyltryptamine ( 2 ), a key starting material in the synthesis of the histone deacetylase inhibitor LBH589 ( 1 ) is described. The reaction of phenylhydrazine ( 7 ) with a stoichiometric amount of 5-chloro-2-pentanone ( 8 ) in aqueous ethanol at reflux furnished crude 2-methyltryptamine ( 2 ). The product 2 was obtained in 47% yield and >99% purity after crystallization from toluene.",10.1021/op7000518,2007-06-08,0.6311162762918393
Organic Letters,An Enantioselective Strategy to Macrocyclic Bisindolylmaleimides. An Efficient Formal Synthesis of LY 333531,[reaction: see text]. The ability to employ a bromo alcohol as a nucleophile in a palladium-catalyzed dynamic kinetic asymmetric transformation leads to an efficient synthesis of a selective PKC inhibitor under clinical development.,10.1021/ol016666v,2001-09-22,0.631113740989614
Synlett,"A New Synthesis of 2-Cyano-6-hydroxybenzothiazole, the Key Intermediate of d-Luciferin, Starting from 1,4-Benzoquinone","2-Cyano-6-hydroxybenzothiazole is the key intermediate for the synthesis of d-luciferin, the natural substrate of firefly luciferases. A new synthesis of 2-cyano-6-hydroxybenzothiazole has been realized starting from the reaction of 1,4-benzoquinone with l-cysteine ethyl ester, followed by oxidation-cyclization of the intermediate ethyl (R)-2-amino-3-(2,5-dihydroxyphenylsulfanyl)propan­oate hydrochloride to 2-carbethoxy-6-hydroxybenzothiazole. A suitable protection of this intermediate and a conversion to the corresponding nitrile gave, after deprotection, 2-cyano-6-hydroxybenzothiazole (32% yield from 1,4-benzoquinone). This nitrile reacts with d-cysteine to afford d-luciferin at room temperature in nearly quantitative yield (90-95%).",10.1055/s-0029-1217971,2009-09-09,0.6311120363053119
Synlett,Concise Synthesis of A Steroid C/D-Ring System Using a Bicyclo[3.2.1]octane Chiral Building Block: A New Route to 25-Hydroxy-Grundmann’s Ketone,A concise route to a steroid C/D-ring system leading to 25-hydroxy-Grundmann’s ketone has been developed along with a new chemical resolution of the chiral starting material containing a bicyclo[3.2.1]octane framework.,10.1055/s-2002-19353,2002-01-01,0.6311092835229573
Organic Letters,"Total Synthesis of Ageladine A, an Angiogenesis Inhibitor from the Marine Sponge <i>Agelas nakamurai</i>",[reaction: see text] A 12-step total synthesis of the tricyclic heteroaromatic marine metabolite ageladine A has been achieved using a 6pi-azaelectrocyclization and a Suzuki-Miyaura coupling of N-Boc-pyrrole-2-boronic acid with a chloropyridine as key steps.,10.1021/ol0602304,2006-02-25,0.6311031175814611
Journal of the American Chemical Society,Synthesis of (−)-Tetracycline,"We describe a convergent, enantioselective synthesis of (-)-tetracycline (1) from benzoic acid (17 steps, 1.1% yield). Benzoic acid was transformed into the AB precursor 2 in 10 steps (11% yield), as previously described, and the latter compound was activated toward Diels-Alder cycloaddition by the introduction of an alpha-phenylthio group (two steps, 66% yield). Heating of the resulting alpha-(phenylthio)enone (3) with the triethylsilyloxybenzocyclobutene derivative 4 at 85 degrees C gave the endo-Diels Alder adduct 5 in 64% yield. Deprotection and oxidation of the latter intermediate gave the 2-(phenylthio)-1,3-diketone 7, which was oxidized with m-chloroperoxybenzoic acid in the presence of trifluoroacetic acid. The sulfoxide intermediate(s) formed eliminated upon warming to 35 degrees C to give the anyhydrotetracycline derivative 8. Intermediate 8 underwent spontaneous autoxidation at 23 degrees C to form the hydroperoxide keto-9 stereoselectively. Without isolation, hydrogenolysis of 9 in the presence of palladium black gave (-)-tetracycline (42% yield from 7), indistinguishable from an authentic sample.",10.1021/ja052151d,2005-05-20,0.6311025656626058
Journal of the American Chemical Society,A Concise Enantioselective Approach to Quassinoids,"A synthetic approach to quassinoids is described. The route to the tetracyclic core relies on an efficient and selective annulation between two unsaturated carbonyl components that is initiated by catalytic hydrogen atom transfer from an iron hydride to an alkene. Application of this strategy allows for enantioselective synthesis of quassin, which is prepared in 14 steps from commercially available starting material.",10.1021/jacs.1c12283,2021-12-27,0.6310737223590058
Organic Process Research & Development,Synthesis of a Bicyclic Piperazine from<scp>l</scp>-Aspartic Acid and Application of a Fluoride-Promoted S<sub>N</sub>Ar Coupling,"The process development is reported of a pivotal C–N bond formation involving ((7 R,9a S )-octahydro-1 H -pyrido[1,2- a ]pyrazin-7-yl)methanol ( 2 ) undergoing nucleophilic aromatic substitution with 3-chlorobenzo[ d ]isoxazole ( 3 ) to furnish ((7 R,9a S )-2-(benzo[ d ]isoxazol-3-yl)octahydro-1 H -pyrido[1,2- a ]pyrazin-7-yl)methanol ( 4 ) as a key intermediate for a family of compounds ( 1 ). Essential to the success of the coupling is the use of fluoride in combination with a phase transfer catalyst. The development of an alternative route to bicyclic piperazine 2 that uses l -aspartic acid ( 20 ) as a starting material to avoid the need for a classical salt resolution is described.",10.1021/op2001854,2011-09-04,0.6310710770669012
Journal of Organic Chemistry,A Synthetic Route to Chiral Tetrahydropyrroloindoles via Ring Opening of Activated Aziridines with 2-Bromoindoles Followed by Copper-Catalyzed C–N Cyclization,"A new synthetic route to nonracemic tetrahydropyrrolo[2,3-b]indoles has been developed via SN2-type ring opening of enantiopure N-activated aziridines with 2-bromoindoles followed by copper-catalyzed C-N cyclization. A series of N-activated aziridines and 2-bromoindole derivatives with different substitution patterns were studied to afford the corresponding tetrahydropyrrolo[2,3-b]indoles in good yields and excellent ee (up to 99%). Highly substituted tetrahydropyrrolo[2,3-b]indole was synthesized as a single stereoisomer (de, ee >99%) from enantiopure trans-disubstituted aziridine.",10.1021/acs.joc.6b01049,2016-07-11,0.6310675125144063
Journal of the American Chemical Society,Total Synthesis of Antheliolide A,"The first synthesis of the structurally unique marine natural product antheliolide A (1) has been accomplished by the pathway outlined in Scheme 1. The sequence is stereocontrolled and has led to the synthesis of (+/-)-1, and ent-1 as well as 1. The route contains a number of noteworthy or novel steps including (1) formation of the mixed acetal 7, (2) the diastereoselective bicyclization to form 8 in which stereocenters are correctly established at each carbon of the four-membered ring, (3) the chain extension 8 --> 11, (4) the efficient closure of the nine-membered ring of 12, (5) the mild oxidative cleavage sequence 14 --> 17, and (6) the successful and quick formation of the last three rings of 1 from aldehyde 17 via 18. The synthesis of 1 has also resulted in the clarification of its absolute configuration, which had not been determined previously.",10.1021/ja066336b,2006-10-06,0.6310617615320441
Synlett,"Total Synthesis of (+)-Tanikolide by a Traceless Stereoinduction Method Using Rhodium(II)-Catalyzed Oxonium Ylide Formation–[2,3]-Sigmatropic Rearrangement and NHC-Catalyzed Ring-Expansion Lactonization","The total synthesis of (+)-tanikolide was accomplished by a traceless stereoinduction method using the key steps of a Rh(II)-catalyzed oxonium ylide formation–[2,3]-sigmatropic rearrangement and an N -heterocyclic carbene-catalyzed ring-expansion lactonization of tetrahydrofurfural. This synthetic route is applicable to the divergent synthesis of tanikolide analogues.",10.1055/s-0035-1561341,2016-01-26,0.6310433994727372
Journal of the American Chemical Society,Concise Total Synthesis of Peyssonnoside A,"Peyssonnoside A is a marine-derived sulfated diterpenoid glucoside with a unique 5/6/3/6 tetracyclic skeleton with a highly substituted cyclopropane ring deeply embedded into the structure. Herein, we report the first total synthesis of this natural product in a concise, efficient, scalable, and highly diastereoselective fashion. The aglucone peyssonnosol was synthesized in 21% overall yield after 15 steps, featuring a Simmons-Smith cyclopropanation and Mukaiyama hydration, fully controlled by the spatial structure of the substrates.",10.1021/jacs.1c07135,2021-08-25,0.6310285517627033
European Journal of Organic Chemistry,"Stereoselective Synthesis of a <i>cis</i>‐1,2‐Dialkylcyclopentane Building Block and Its Application in Isoprostane Synthesis (5‐<i>ent</i>‐F<sub>2c</sub>‐IsoP)","Abstract The all‐ cis substituted cyclopentane 3a , an analogue of the Corey lactone, has been prepared from a readily available nortricyclanone derivative by a five‐step sequence in an overall yield of 34 %. This chiral building block has been applied in total syntheses of two diastereomeric isoprostanes belonging to the 5‐F 2 family: ent ‐5‐F 2c ‐IsoP ( ent ‐ 1 ) and 5‐ epi ‐ ent ‐5‐F 2c ‐IsoP ( ent ‐ 2 ). Key features of the syntheses are the introduction of the two unsaturated alkyl side chains through an E ‐selective Horner–Wadsworth–Emmons reaction with the base‐sensitive syn ‐aldehyde 10 , along with a Z ‐selective Wittig olefination.(© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2008)",10.1002/ejoc.200800010,2008-04-01,0.6310237265244142
Angewandte Chemie International Edition,A Synthesis‐Driven Structure Revision of Berkelic Acid Methyl Ester,A subtle difference: A single step suffices to transform a linear precursor into the chromane spiroketal core of the metalloproteinase-3 inhibitor berkelic acid by an acid-catalyzed deprotection/Michael addition/acetalization cascade. This efficient route resulted from the realization that the originally proposed structure is neither thermodynamically nor kinetically favored and has led to revision of the structure (denoted in red).,10.1002/anie.200803339,2008-09-24,0.6310178729881192
Organic Process Research & Development,Process Development of the Novel LpxC Inhibitor T-1228. Part 1: Synthesis of the Diol Fragment,"The novel LpxC inhibitor T-1228 is a candidate drug molecule for multidrug-resistant Gram-negative bacterial infection. This report describes the synthesis of the diol unit of T-1228, ( S )-1-(4-ethynylphenyl)ethane-1,2-diol, from commercially available 2-bromo-1-(4-iodophenyl)ethan-1-one, achieved in 5 steps and 4 isolations. The stereogenic center of the diol unit was created by means of a highly scalable form of the Corey–Bakshi–Shibata reduction; process parameters were optimized using the Design of Experiments methodology. Using this newly developed process chemistry route, we successfully synthesized 12.5 kg of ( S )-1-(4-ethynylphenyl)ethane-1,2-diol in 60% total yield and optical purity >99% ee.",10.1021/acs.oprd.5c00165,2025-10-23,0.63100932915401
Organic Letters,Total Synthesis of (−)-α-Kainic Acid by (−)-Sparteine-Mediated Asymmetric Deprotonation−Cycloalkylation,"[reaction: see text] We report a new enantioselective synthesis of (-)-alpha-kainic acid from d-serine methyl ester hydrochloride, based on a (-)-sparteine-mediated asymmetric deprotonation of an intermediate carbamate that, by stereospecific anti S(N)'S(E)' intramolecular cycloalkylation, leads to the pyrrolidine ring precursor of (-)-alpha-kainic acid, in high yield and diastereoselectivity. The intermediate pyrrolidine was further transformed to (-)-alpha-kainic acid in three steps.",10.1021/ol0485666,2004-09-21,0.6310015026579296
Organic Letters,An Outside-In Approach to Adjacent Bistetrahydrofuran Annonaceous Acetogenins with <i>C</i><sub>2</sub> Core Symmetry. Total Synthesis of Asimicin and a C32 Analogue,[reaction: see text] A synthesis of the Annonaceous acetogenin asimicin and a side-chain analogue has been achieved by a highly convergent route in which Grubbs cross-metathesis plays a key role.,10.1021/ol061352z,2006-07-06,0.630999452307211
Tetrahedron,A six-step synthesis of (S)-5-ethenyl-3-(1-methyl-2-pyrrolidinyl)pyridine (SIB-1508Y) from (S)-nicotine,,10.1016/j.tetlet.2005.12.085,2006-01-10,0.6309724327741587
Organic Process Research & Development,"Chemical Development of an α2δ Ligand, (3<i>S</i>,5<i>R</i>)-3-(Aminomethyl)-5-methyloctanoic Acid","Three synthetic approaches, suitable for the large scale manufacture of the α2δ-ligand, (3 S,5 R )-3-(aminomethyl)-5-methyloctanoic acid 3, have been evaluated. The selected seven step manufacturing process has then been optimized and used to deliver over 20 kg of API; salient features of the synthesis include the use of 4,4,4-trimethoxybutyronitrile as an efficient four carbon amino acid equivalent. Highly selective kinetic resolution of the C3 stereocentre was accomplished via diastereoselective hydrolysis of a cyanoester intermediate using Amano Lipase PS-SD. Extensive process optimisation of the route starting from ( R) -2-methylpentanol, led to significant improvements through telescoping, with less than 62 kg of solvent being needed to produce 1 kg of API.",10.1021/op2001832,2011-08-30,0.6309682286664703
Organic Process Research & Development,Development of a Kilogram-Scale Synthesis of a Key Ulevostinag Subunit Part II: An Electrophilic Approach to Fluorinated Nucleosides,"Ulevostinag (MK-1454) is a potent cyclic dinucleotide stimulator of interferon genes (STING) that was selected as a clinical candidate for evaluation in multiple solid tumor types. Nucleoside analogue 3′-deoxy-3′-α-fluroguanosine (3′FG) is one of two key monomeric subunits comprising Ulevostinag, and its efficient preparation was set as a key deliverable in the development of this novel therapeutic. We recently reported a novel synthetic approach to 3′FG, involving the aminocatalytic electrophilic fluorination and subsequent substrate-directed reduction of an isolable 2′-keto-nucleoside ( i -Bu-3 ). Herein, we describe the process development of these key stereodefining steps, enabling the kilogram-scale preparation of i -Bu-3′FG ( 1 ). Key features of this process include (1) identification of commercially available l -leucine amide as an excellent fluorination catalyst, (2) development of a highly stereoselective (>95:5) intramolecular hydride delivery from the hindered nucleoside β-face, and (3) use of dispersive Raman spectroscopy to guide form control during the crystallization of 1 .",10.1021/acs.oprd.2c00395,2023-03-07,0.6309651072396509
Journal of Organic Chemistry,A Representative Synthetic Route for C5 Angucycline Glycosides: Studies Directed toward the Total Synthesis of Mayamycin,"This study discloses an efficient synthetic route for the regiospecific construction of a C5 glycoside angucycline representative of mayamycin. The key steps are intramolecular aldol condensation and Hauser annulation, and the key precursor for the aldol reaction is accessible through utilization of α-lithiation of a vinyl ether.",10.1021/acs.joc.7b02833,2017-12-12,0.6309618948244113
Journal of Organic Chemistry,An Expedient Route to Montanine-Type Amaryllidaceae Alkaloids: Total Syntheses of (−)-Brunsvigine and (−)-Manthine,"The first total syntheses of (-)-brunsvigine (1) and (-)-manthine (2) were accomplished in 10 and 18 steps, respectively. (-)-Quinic acid was converted to enone 12 in five steps. Iodination of enone 12 followed by stereoselective reduction yielded alpha-iodo allylic alcohol 16. Conversion of alcohol 16 into Weinreb amide 11 followed by anionic cyclization gave bicyclic enone 10. Stereoselective reduction of enone 10 and subsequent protection afforded pivaloate 9. Grignard addition of 8 to 9 and detosylation afforded amine derivative 19. Pictet-Spengler cyclization of 19 with Eschenmoser's salt and subsequent hydrolysis gave enantiomerically pure (-)-brunsvigine (1). For the total synthesis of (-)-manthine (2), the key intermediate 7 was hydrolyzed to diol 21. Conversion of 21 into 22 followed by regioselective cleavage with DIBAL furnished alcohol 25. Alcohol 25 was converted to the corresponding triflate 26, which on treatment with CsOAc and 18-crown-6 gave stereoinverted acetate 27. Hydrolysis of acetate 27 followed by methylation afforded compound 29. Detosylation of 29 afforded amine derivative 30. Pictet-Spengler cyclization of 30 followed by debenzylation gave alcohol 33. Finally, methylation of alcohol 33 afforded (-)-manthine (2).",10.1021/jo801089y,2008-09-10,0.630961109143507
European Journal of Organic Chemistry,The First Synthesis of (–)‐Agelasine F; an Antimycobacterial Natural Product Found in Marine Sponges in the <i>Agelas</i> Genus,(–)‐Agelasine F (also known as ageline A) is a diterpene‐adenine hybrid natural product isolated from marine sponges ( Agelas species) and this compound is known to display cytotoxic activity against a variety of cancer cell lines as well as microorganisms. We herein report the first total synthesis of (–)‐agelasine F. The commercially available and inexpensive monoterpenoid ( S )‐carvone was found to be a highly suitable starting material for the construction of the terpenoid part of the desired agelasine and controlling the stereochemistry of the target compound. Two alternative strategies from ( S )‐carvone were evaluated. Key‐intermediates in the (–)‐agelasine F synthesis are believed also to be valuable starting materials for total syntheses of other bioactive marine sponge metabolites. The synthetic route to (–)‐agelasine F described herein is more efficient than previously published syntheses of racemic or ent ‐agelasine F.,10.1002/ejoc.202000202,2020-03-11,0.6309553155917876
Synlett,"Asymmetric Synthesis of cis-(S,R)-3-Amino-4-fluoro-1-methylpyrrolidine","The development of the stereoselective synthesis of cis-(S,R)-3-amino-4-fluoro-1-methylpyrrolidine is described starting from chiral, non-racemic 1-[(3S,4S)-3-azido-4-hydroxypyrrolidin-1-yl]-2,2,2-trifluoroethan-1-one. Two sets of deoxyfluorination conditions are developed for achieving inversion of the chiral center with high or complete stereoselectivity.",10.1055/s-0037-1611553,2019-05-20,0.6309400406559365
Journal of Organic Chemistry,Total Synthesis of Oxidized Phospholipids. 3. The (11<i>E</i>)-9-Hydroxy-13-oxotridec-11-enoate Ester of 2-Lysophosphatidylcholine,"A total synthesis of (11E)-9-hydroxy-13-oxotridec-11-enoate ester of 2-lysophosphatidylcholine (HOT-PC) was devised to facilitate identification of this oxidized phospholipid. A lactone, 8-(3-oxo-1H,6H-2-oxinyl)octanoic acid (1), believed to be generated through an intermediate (11E)-9-hydroxy-13-oxotridec-11-enoic acid (HOT), is produced upon autoxidation of linoleic acid. A synthesis of lactone 1 methyl ester was accomplished from HOT involving a novel trans-cis isomerization that is driven to completion by cyclization to a hemiacetal. An alternative route to this carbon skeleton was also achieved that provides the lactone 1 itself.",10.1021/jo000809u,2000-08-31,0.6309324873529271
Synlett,Thieme Chemistry Journal Awardees - Whereare They Now? Efforts towards the Total Synthesis of Vinigrol,A strategy for the total synthesis of vinigrol is detailed with two key steps - oxidative dearomatization and intramolecular Diels-Alder cycloaddition - providing the cis-decalin core. A novel and mild means for the formation of ortho-quinone methides is also described.,10.1055/s-0028-1087378,2008-12-12,0.630918448929477
Organic Process Research & Development,Development of a Process for a Chiral Aminochroman Antidepressant:  A Case Story,"The authentic development aiming at a full-scale method for the new chemical entity ebalzotan (code name NAE-086), a selective 5HT 1A -agonist chosen as an Astra candidate drug primarily for the treatment of depression and anxiety is described. As it turned out, largely due to severe time constraints the original Medicinal Chemistry route of synthesis comprising 13 steps arranged in linear fashion (starting from 3-methoxyphenol) and including a “classical” diastereomer resolution to generate the desired ( R )-enantiomer had to be scaled up without sufficiently developed methods at hand. This resulted in an extended batch cycle time of 5 months after which time a very poor overall yield of 0.25% (!) could be isolated, albeit the product showed excellent stereochemical purity of 99.9% ( R ). Starting from this deploring position a process was designed which proved to operate well in a 400−600 L pilot scale affording ∼27 kg of high quality material.",10.1021/op000041f,2000-08-26,0.6309155230562321
Synthesis,Total Synthesis of Enisorine D and its Analogues,"The first total synthesis of enisorine D, a natural product isolated from the marine sponge Iotrochota cf. iota, is described in 64% overall yield. The target molecule, which is an inhibitor of T3SS-dependent Yope secretion of Y. pseudotuberculosis, is achieved in seven linear steps from tyramine via simple and effective transformations that include bromination, acylation, alkylation, azidation, reduction and routine acid–amine coupling. A total of sixteen analogues are prepared by coupling with eight different cinnamic acids, two bromopyrrole carboxylic acids, five phenyl carboxylic acids and picolinic acid.",10.1055/s-0039-1690025,2019-09-23,0.6309030283065585
Journal of Organic Chemistry,"Synthesis of Methoxyfumimycin with 1,2-Addition to Ketimines","The synthesis of (+/-)-methoxyfumimycin, a potential new bacterial peptide deformylase (PDF) inhibitor, is reported. To generate the stereogenic fully substituted carbon, the key step is a 1,2-addition of a methyl Grignard reagent to a ketimine. The overall synthetic strategy involves a Dakin oxidation of a vanillin derivative, Friedel-Crafts acylation, Claisen rearrangement, lactonization, and rhodium-catalyzed olefin isomerization.",10.1021/jo902026s,2009-12-03,0.6308516651496725
Tetrahedron,"(1E,3E)-4-acetoxy-1-phenyldimethylsilyl-1,3-butadiene as a surrogate for (1E,3E)-1,4- diacetoxy-1,3-butadiene: a highly efficient synthesis of (±)-shikimic acid",,10.1016/s0040-4039(00)98012-2,1990-01-01,0.6308442499551031
Journal of Organic Chemistry,"Asymmetric One-Pot Synthesis of (3<i>R</i>,3a<i>S</i>,6a<i>R</i>)-Hexahydrofuro[2,3-<i>b</i>]furan-3-ol: A Key Component of Current HIV Protease Inhibitors","A concise and efficient synthesis of (3R,3aS,6aR)-hexahydrofuro[2,3-b]furan-3-ol, a key building block for several clinical and experimental HIV protease inhibitors including the highly important drug darunavir, was achieved via a one-pot procedure using furan and Cbz-protected glycol aldehyde as starting materials. A [2+2]-photocycloaddition between both reactants which can be prepared from wood-based starting materials according to the principles of xylochemistry, followed by hydrogenation and lipase-catalyzed kinetic resolution afforded the target compound in high yield and up to 99% ee.",10.1021/acs.joc.6b02588,2016-12-20,0.630835215353737
Organic Process Research & Development,"An Expedient Synthesis of LAF389, a Bengamide B Analogue","An optimized, convergent, safe synthesis of LAF389 ( 9 ), an anti-cancer agent analogous to bengamide B, is described. Starting from α- d -glucoheptonic ( d -glycero- d -gulo-heptonic acid) γ-lactone ( 10 ), the lactone 15 was constructed in five steps. Major improvements were made in the preparation of the aldehyde precursor 14 and subsequent olefination to yield 15 via a modified Julia protocol. This olefination was significantly improved by using TMSCl as an additive. The second fragment of the drug substance, ε-caprolactam 7, was obtained in two one-pot operations from (5 R )-5-hydroxy- l -lysine ( 1 ). Finally, opening 15 with 7 using sodium 2-ethyl hexanoate (Na-EH) gave 8, which on deprotection yielded LAF389.",10.1021/op0341162,2003-09-23,0.6308114222856785
Journal of Organic Chemistry,Synthesis of Oxa-Bridged Analogues of Farnesyltransferase Inhibitor RPR 115135,"Two synthetic routes to new oxygen-bridged analogues of farnesyltransferase inhibitors are described that follow either a [3 + 2]/[4 + 2] or a [4 + 2]/[3 + 2] sequence of reactions. The first approach has been achieved by reacting the in situ generated phenylisobenzofuran (PIBF) 4 with pyrroline 5a and has led stereoselectively to racemic 18, which was transformed in a few steps into the target molecule 2. The second pathway relies on a key intermediate 6, obtained either by condensation of PIBF with methyl acrylate, followed by a deprotonation/selenation and an oxidation/elimination sequence, or by cycloaddition between PIBF and alpha-phenylselenoacrylate 11, followed by the same oxidation/elimination sequence. The reaction of 6 with amino dipole 7 gives diastereoselective access to pyrrolidine 25, a precursor of the second target 3, an epimer of 2.",10.1021/jo0100188,2001-05-10,0.6307865605322087
Tetrahedron,Total synthesis of the aromatase inhibitor dihydroisocoumarin via protective opening of lactones,,10.1016/j.tetlet.2012.05.012,2012-05-11,0.6307754394387038
Journal of Organic Chemistry,Synthesis of Isoplagiochin A,"An unambigous synthesis of the title compound ( 1 ) was carried out in 23 steps following a convergent scheme involving, as the key step, macrocyclization by an intramolecular Wittig reaction.",10.1021/jo9620829,1997-05-01,0.6307672964345621
Synthesis,First Highly Efficient Asymmetric Synthesis of the<i>Hyrtios Erectus</i>Diketotriterpenoid,"The first highly efficient asymmetric synthesis of the diketotriterpenoid 1, isolated from the Indonesian marine sponge Hyrtios erectus, in good overall yield and employing simple starting materials such as butanone, is described. Both stereogenic centres at the C-6 and C-19 positions of the C 2-symmetrical molecule were generated via α-alkylation employing the SAMP/RAMP hydrazone method with high asymmetric inductions (de, ee ≥ 96%). The absolute configuration of the natural material was determined as R,R.",10.1055/s-2002-34949,2002-01-01,0.630760029688807
Journal of the American Chemical Society,Total Synthesis of (+)-Aspidospermidine:  A New Strategy for the Enantiospecific Synthesis of Aspidosperma Alkaloids,"A new strategy was developed for the enantiospecific synthesis of aspidosperma alkaloids. The key steps involve a novel ketene-lactonization reaction of a chiral vinyl sulfoxide to efficiently set up the quaternary carbon center, and a tandem Michael addition-alkylation reaction sequence to form the polycyclic core structure. This new strategy was employed in the total synthesis of natural product (+)-aspidospermidine.",10.1021/ja026357f,2002-10-22,0.6307420665138707
Journal of the American Chemical Society,"Scalable, Divergent Synthesis of Meroterpenoids via “Borono-sclareolide”","A scalable, divergent synthesis of bioactive meroterpenoids has been developed. A key component of this work is the invention of ""borono-sclareolide"", a terpenyl radical precursor that enables gram-scale preparation of (+)-chromazonarol. Subsequent synthetic operations on this key intermediate permit rapid access to a variety of related meroterpenoids, many of which possess important biological activity.",10.1021/ja303937y,2012-05-14,0.6307188363918318
Synlett,A Short Synthesis of (+)-Bakuchiol,"The concise enantioselective total synthesis of (+)-bakuchiol has been achieved using an asymmetric 1,4-addition to construct its all-carbon chiral quaternary center based on the induction of chirality by the (2′ S )-2′-phenyloxazolidinone auxiliary, followed by a one-pot transformation under aldol reaction conditions. The synthesis was completed in four steps from ( E )-geranic acid in an overall yield of 53%.",10.1055/s-0033-1338968,2013-07-26,0.6307073877912324
Journal of Organic Chemistry,"Stereoselective Synthesis of 2‘-Amino-2‘,3‘-dideoxynucleosides by Nitrone 1,3-Dipolar Cycloaddition:  A New Efficient Entry Toward d4T and Its 2-Methyl Analogue","An efficient access to 2'-(dimethylamino)-2',3'-dideoxynucleosides is reported. The synthetic strategy relies on the 1,3-dipolar cycloaddition of C-alkoxycarbonyl nitrones to allyl acetate, followed by reductive ring opening to substituted lactones, DIBALH reduction to the corresponding 3-(dimethylamino)tetrahydro-2-furanols, and coupling with silylated thymine. The removal of the dimethylamino group by Cope elimination affords a new formal synthesis of d4T and analogous unsaturated 2',3'-dideoxynucleosides.",10.1021/jo972264i,1998-12-19,0.6307000489272152
Tetrahedron,"A new and improved synthesis of a potential antitumour 7h-pyrido[4,3-c ]carbazole analog.",,10.1016/s0040-4039(00)94988-8,1985-01-01,0.6306941029207718
Angewandte Chemie International Edition,A Chiral Pool Based Synthesis of Platensimycin,"Extensive pharming: An expedient entry into the tetracycle 2, a late-stage synthetic intermediate en route to the broad-spectrum antibiotic (−)-platensimycin (1) has been accomplished. The strategy involves a series of cyclizations starting from the inexpensive chiral pool starting material (R)-(−)-carvone.",10.1002/anie.200705080,2008-01-04,0.6306770960193123
Journal of Organic Chemistry,Protecting-Group-Free Total Synthesis of Chatenaytrienin-2,"An efficient seven-step, protecting-group-free first total synthesis of chatenaytrienin-2 based on ring-closing metathesis and C(sp)–C(sp 3 ) Sonogashira coupling with a 36.5% overall yield has been described. The ready availability of starting materials and key Wittig olefination, ring-closing metathesis, Lindlar reduction, and C(sp)–C(sp 3 ) coupling makes this strategy applicable for the synthesis of various unbranched polyene-natural products with 1,5,9, n -( Z )-configured double bonds.",10.1021/acs.joc.9b01952,2019-09-02,0.6306731506776568
Journal of Organic Chemistry,Exploration of a Nitromethane-Carbonylation Strategy during Route Design of an Atropisomeric KRAS<sup>G12C</sup> Inhibitor,"Route design and proof of concept synthesis was conducted on a synthetically challenging atropisomeric KRAS G12C inhibitor to support clinical API manufacture. Improvements to the synthesis of a chiral piperazine fragment gave reduced step count and streamlined protecting group strategy via the formation and methanol ring opening of an N -carboxy-anhydride (NCA). The complex atropisomeric nitroquinoline was accessed via an early stage salt-resolution followed by a formal two-part nitromethane-carbonylation, avoiding a high temperature Gould–Jacobs cyclization that previously led to atropisomer racemization. The substrate scope of the formal nitromethane-carbonylation strategy was further explored for a range of ortho -substituted bromo/iodo unprotected anilines.",10.1021/acs.joc.1c01736,2021-10-15,0.6306678527016393
European Journal of Organic Chemistry,Diversity‐Oriented Synthesis of Calothrixins and Ellipticines,Abstract The divergent synthesis of calothrixins and ellipticines has been accomplished by utilising the one‐pot formation of o ‐diacylarenes as a key intermediate through rearrangement of o ‐hydroxy ketone monoacyl hydrazones by lead tetraacetate mediated oxidation.,10.1002/ejoc.201402837,2014-09-19,0.6306600293399943
European Journal of Organic Chemistry,"Convenient Synthesis of the Antibiotic Linezolid via an Oxazolidine‐2,4‐dione Intermediate Derived from the Chiral Building Block Isoserine","Abstract We describe a new synthesis of the 5‐(aminomethyl)oxazolidin‐3‐one core of linezolid in enantiomerically pure form. The expedient cyclization of the α‐hydroxy amide derived from isoserine and 3‐fluoro‐4‐morpholinoaniline to give the corresponding (aminomethyl)oxazolidine‐2,4‐dione, followed by its mild selective reduction at the C(4)‐position, gave linezolid in almost quantitative overall yield.",10.1002/ejoc.201402888,2014-10-28,0.6306547356358677
Angewandte Chemie International Edition,Total Syntheses of (+)‐Grandilodine C and (+)‐Lapidilectine B and Determination of their Absolute Stereochemistry,"Enantioselective total syntheses of the Kopsia alkaloids (+)-grandilodine C and (+)-lapidilectine B were accomplished. A key intermediate, spirodiketone, was synthesized in 3 steps and converted into the chiral enone by enantioselective deprotonation followed by oxidation with up to 76 % ee. Lactone formation was achieved through stereoselective vinylation followed by allylation and ozonolysis. The total synthesis of (+)-grandilodine C was achieved by palladium-catalyzed intramolecular allylic amination and ring-closing metathesis to give 8- and 5-membered heterocycles, respectively. Selective reduction of a lactam carbonyl gave (+)-lapidilectine B. The absolute stereochemistry of both natural products was thereby confirmed. These syntheses enable the scalable preparation of the above alkaloids for biological studies.",10.1002/anie.201510561,2016-02-02,0.6306517944235474
Organic Process Research & Development,Development of a Commercial Process to Produce Oxandrolone,"A manufacturing scale process for the preparation of the anabolic steroid Oxandrolone was developed. Key elements included the following: the bromination of methylandrostanolone with perbromide to give the 2-bromoketone in ca. 80% yield with minimal dehydration, subsequent elimination of the bromide with Li 2 CO 3 /LiBr to give the 2-enone in ca. 70% yield with minimal formation of methyltestosterone, and an ozonolysis procedure to give the penultimate intermediate in ca. 90% yield. The overall yield from methylandrostanolone to Oxandrolone using the described process was 45% as compared to the original Searle yield of 8%.",10.1021/op060231b,2007-04-20,0.6306510346149018
Synlett,A Short Enantioselective Total Synthesis of (-)-Linderol A<b />,"An efficient short enantioselective total synthesis of (-)-linderol A was achieved via a five-step reaction with 30% overall yield, starting from 4-methoxyphloroacetophenone.",10.1055/s-2007-1000834,2007-12-19,0.6306436589348015
Angewandte Chemie International Edition,Artificial‐Intelligence‐Driven Organic Synthesis—En Route towards Autonomous Synthesis?,AI for chemistry: Automated synthesis can now be performed using an artificial intelligence algorithm to propose the synthetic route and a robotic microfluidic platform to execute the synthesis. This Highlight describes this approach towards small-molecule synthesis and reflects on the significance of this milestone in chemistry.,10.1002/anie.201911062,2019-10-22,0.6306265403225616
Organic Process Research & Development,"Amidation and N-Boc Deprotection Process Improvement for the Preparation of 5-(1-Piperazinyl)benzofuran-2-carboxamide, a Key Intermediate of Vilazodone","An improved process for the preparation of 5-(1-piperazinyl)benzofuran-2-carboxamide, a key intermediate used in the synthesis of antidepressant drug vilazodone is reported.",10.1021/op500070t,2014-04-15,0.6306122777272488
Synlett,A First Generation Total Synthesis of (+)-Salicylihalamide A,"All articles of this category An efficient total synthesis of (+)-salicylihalamide ( 1 ) is described. The synthetic strategy features a highly E -selective ring-closing metathesis to construct the 12-membered salicylihalamide. A macrocycle and a practical method for installation of the labile ene-hepta-( Z , Z )-dienamide side chain, which relies on a Curtius rearrangement to forge the C18-N bond with subsequent N -acylation. salicylihalamide - total synthesis - macrocycles - metathesis - Curtius rearrangement",10.1055/s-2001-14651,2001-01-01,0.6306082756275412
Synlett,An Improved Synthesis of ResorcylicAcid Macrolactone Inhibitors of Hsp90,"A synthesis of resorcylic acid macrolactone analogues of the natural product radicicol is described in which the key steps are the acylation and ring opening of a homophthalic anhydride to give an isocoumarin, followed by a ring-closing metathesis to form the macrocycle.",10.1055/s-0029-1217329,2009-06-02,0.630602999173645
Tetrahedron,A convergent asymmetric synthesis of γ-butenolides,,10.1016/s0040-4039(99)01242-3,1999-08-01,0.630597930469148
Tetrahedron,A short synthesis of an important precursor to a new class of bicyclic β-lactamase inhibitors,A short synthesis of an important precursor to known bicyclic β-lactamase inhibitors is described. The synthesis uses commercially available trans-3-hydroxy-l-proline 1. Protection of the amino group followed by formation of the hydroxamate and cyclization using Mitsunobu conditions afforded bicyclic β-lactam 4 in three steps in 53% overall yield.,10.1016/s0040-4039(96)02264-2,1997-01-01,0.6305901182407715
Tetrahedron,"Convergent synthesis of 2,3-bisarylpyrazolones through cyclization of bisacylated pyrazolidines and hydrazines",,10.1016/j.tetlet.2006.03.063,2006-03-30,0.6305853666016997
European Journal of Organic Chemistry,"Stereoselective Total Synthesis of (–)‐Batzellasides A, B, and C","Abstract Total synthesis of (–)‐ L ‐batzellasides A, B, and C has been achieved in 13 steps from known lactone 2 in 12.6, 13.2, and 13.8 % overall yields, respectively. The key steps in this synthesis were the stereoselective introduction of an allyl group at the C1 position by acyliminium chemistry and Brown's asymmetric allylation of the corresponding aldehydes to construct a stereocenter on the side chain.",10.1002/ejoc.201201567,2013-03-19,0.6305747465303254
Tetrahedron,"A novel synthesis of 2,3-epoxy-3-arylpropanol via arsonium salt",,10.1016/s0040-4039(00)80741-8,1988-01-01,0.6305714150957152
Journal of Organic Chemistry,"Enantioselective Synthesis of α,α-Disubstituted Amino Acid Derivatives <i>via</i> Enzymatic Resolution:  Preparation of a Thiazolyl-Substituted α-Methyl α-Benzyl Amine","A new and efficient enantioselective synthesis of the (S)-alpha,alpha-disubstituted phenethylamine 1 via Lipase resolution of the esters 3 and 4 is described. The effect of pH, enzyme load, and solubilizing additives has been studied and optimized. Conversion of the carboxylic acid 10 to the desired thiazole 1 is accomplished in high overall yield via an intermediate oxazolinone 13. This facile process requires only a single chromatographic step, and multigram quantities of 1 have been prepared.",10.1021/jo9610671,1996-01-01,0.6305483885554849
European Journal of Organic Chemistry,Enantioselective Total Synthesis of (+)‐Hagen's Gland Lactones,Abstract Enantioselective synthesis of Hagen's gland lactone is described. The enantiomerically enriched diol was prepared by organocatalytic α‐oxidation of the aldehyde. The other key reactions involved a highly diastereoselective intramolecular cyclopropanation of vinylogous carbonates to furnish donor–acceptor‐substituted cyclopropanes and their ring opening and iodolactonization followed by reduction.,10.1002/ejoc.201101328,2011-10-14,0.6305347871761278
Tetrahedron,On the formation of longmers in phosphorothioate oligodeoxyribonucleotide synthesis,,10.1016/s0040-4039(97)00798-3,1997-06-01,0.6305322505719327
Journal of Organic Chemistry,"New Access to Indolizidine and Pyrrolizidine Alkaloids from an Enantiopure Proline:  Total Syntheses of (−)-Lentiginosine and (1<i>R</i>,2<i>R</i>,7a<i>R</i>)-Dihydroxypyrrolizidine","A new approach to the synthesis of indolizidine and pyrrolizidine skeletons is reported. (-)-Lentiginosine and (1R,2R,7aR)-dihydroxypyrrolizidine have both been synthesized in 13 steps from di-O-isopropylidene-d-mannitol. The common key intermediate is (-)-dihydroxyproline benzyl ester 10.",10.1021/jo070462w,2007-06-28,0.6305288915871241
Journal of the American Chemical Society,Total Synthesis of (±)-Gelsemoxonine,"Gelsemoxonine (1) is a Gelsemium alkaloid incorporating an unusual azetidine. Its total synthesis was achieved employing a novel ring contraction of a spirocyclopropane isoxazolidine to furnish a β-lactam intermediate. This β-lactam ring was further elaborated into the azetidine of Gelsemoxonine. In addition, the synthesis includes a highly diastereoselective reductive Heck cyclization for the installation of the oxindole ring system as well as a directed hydrosilylation of an alkyne to access the ethyl ketone of the natural product.",10.1021/ja403823n,2013-05-21,0.6305263070965302
Organic Process Research & Development,Stereoselective Synthesis of TAFIa Inhibitors: Strategic Application of Asymmetric Hydrogenation for the API and Crystallization-Induced Asymmetric Transformation for Its Prodrug,"This study details the development of manufacturing processes for TAFIa (activated thrombin-activatable fibrinolysis inhibitor) inhibitor 1 and its prodrug 2 . To establish an industrial-scale production process for 1, a comprehensive screening of chiral catalysts for an asymmetric hydrogenation of intermediate 12 was conducted. This effort revealed that Ru/BINAP catalyst system in fluorous alcohol solvents (2,2,2-trifluoroethanol (TFE) and 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP)) significantly improves both reactivity and selectivity. As a result, a practical and efficient process was successfully constructed, achieving 85% overall yield from intermediate 12 over 5 steps. This represents a notable increase compared to the early stage process (40% overall yield in 5 steps from intermediate 12 ). In parallel, a manufacturing process was developed for prodrug 2 . A novel optically active prodrug fragment, ( R )- 32 –utilizing HFIP as a leaving group–was designed to avoid a troublesome chromatographic process, and its synthetic route was established. Enzyme screening identified Chirazyme L-2, C4 as an effective choice, producing ( R )- 32 in 37% yield with an optical purity of 99.8% ee . A racemization method utilizing catalytic amount of Ac 2 O was combined with the crystallization of the desired isomer 2 utilizing diastereomer mixture of 2c (( R, R )- and ( R, S )-forms). Crystallization-induced asymmetric transformation (CIAT) from ( R, R )-form to the desired ( R, S )-form was achieved, resulting in 97% yield with 94.8% de . Building on these methods, a manufacturing process was established for prodrug 2, attaining an overall yield of 74% from intermediate 12 through 6 steps.",10.1021/acs.oprd.5c00379,2025-11-13,0.6305246593823458
Journal of the American Chemical Society,Total Synthesis and Structural Revision of (+)-Amphidinolide W,"An enantioselective first total syntheis of amphidinolide W (2) and a revision of its C6 absolute stereochemistry (1) are described. Amphidinolide W (1), a 12-membered macrolide isolated from Amphidinium sp., has shown potent antitumor properties against a variety of NCI tumor cell lines. The synthesis is convergent, and four of the five chiral centers were derived through asymmetric synthesis. The synthesis features Sharpless asymmetric dihydroxylation, diastereoselective alkylation, efficient cross metathesis of functionalized substrates, and novel functional group transformations using selective lipase-catalyzed hydrolysis of the primary acetate group. Of particular note, the C6 absolute stereochemistry of amphidinolide W (1) has now been revised through our current synthesis.",10.1021/ja049754u,2004-03-01,0.630524316270985
Journal of Organic Chemistry,"Methods for the Synthesis of 5,6,7,8-Tetrahydro-1,8-naphthyridine Fragments for α<sub>V</sub>β<sub>3</sub> Integrin Antagonists","The preparation of 3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propan-1-amine 2a and 3-[(7R)-7-methyl-5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl]propan-1-amine 2b, key intermediates in the synthesis of alpha(V)beta(3) antagonists, is described. The syntheses rely on the efficient double Sonogashira reactions of 2,5-dibromopyridine 3 with acetylenic alcohols 4a/4b and protected propargylamines 10a-e followed by Chichibabin cyclizations of 3,3'-pyridine-2,5-diyldipropan-1-amines 9a/9b.",10.1021/jo0486950,2004-11-13,0.6305181742042723
Tetrahedron,Studies in biomimetic polyether synthesis: Synthesis of an A-ring subunit of etheromycin,,10.1016/s0040-4039(00)79360-9,1993-07-01,0.6305145526793657
Tetrahedron,Studies in marine macrolide synthesis: Stereocontrolled synthesis of the F-ring subunit of spongistatin 1 (altohyrtin A),,10.1016/s0040-4039(97)01257-4,1997-08-01,0.6305145526793657
Journal of Organic Chemistry,Asymmetric Synthesis of (−)-Swainsonine,"We report a new asymmetric synthetic method for (-)-swainsonine utilizing a chiral oxazoline precursor. The key features in this strategy are the diastereoselective oxazoline formation reaction catalyzed by palladium(0), diasteroselective dihydroxylation, and the stereocontrolled allylation reaction with TiCl(4).",10.1021/jo802800d,2009-04-10,0.630511890874596
European Journal of Organic Chemistry,A New Approach to the Total Synthesis of Rosuvastatin,"Abstract A new multi‐step synthesis of the lipid‐lowering agent rosuvastatin, involving two homogeneously catalyzed reaction steps, is described. The key building block, N ‐[4‐(4‐fluorophenyl)‐5‐formyl‐6‐isopropylpyrimidin‐2‐yl]‐ N ‐methylmethanesulfonamide ( 2 ), was prepared by Pd‐catalyzed formylation with CO/H 2 (1:1, 50 bar, phosphane ligand/substrate ratio of 1:10). Several alternative pathways for the preparation of 2 were also tested, but were found to be inferior. Rosuvastatin precursor 1 was assembled by Wittig coupling of aldehyde 2 and ylide ( R )‐ 3 , derived from a Ru‐catalyzed asymmetric hydrogenation. The second stereogenic center was finally created by stereoselective reduction with Et 2 BOMe and NaBH 4 to afford rosuvastatin ethyl ester. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2008)",10.1002/ejoc.200700813,2007-11-12,0.6305010912926039
Organic Process Research & Development,Process Intensification and Integration Studies for the Generation of a Key Aminoimidazole Intermediate in the Synthesis of Lanabecestat,"An improved synthetic procedure for the multistep synthesis of aminoimidazole 6, a key intermediate in the preparation of lanabecestat (AZD3293/LY3314814), is described. Under intensified conditions (high temperature and elevated pressure), the overall processing time and required amounts of reagents could be significantly reduced, thus potentially minimizing manufacturing costs and improving the sustainability footprint. Process integration of three sequential steps starting from ketone intermediate 2 has been attempted to set the stage for a potential multistep continuous manufacturing route. The process consists of initial formation of imine 3 by treatment of ketone 2 with ammonia and Ti( i PrO) 4, cyclocondensation of 3 with thioamide 4 to form thiol 5, and aminolysis using ammonia and Zn(OAc) 2, allowing the target building block 6 to be accessed in 47% overall yield.",10.1021/acs.oprd.8b00089,2018-04-26,0.6304877970974232
Organic Letters,"Stereoselective Total Synthesis of Atractylodemayne A, a Conjugated 2(<i>E</i>),8(<i>Z</i>),10(<i>E</i>)-Triene-4,6-diyne","The first total synthesis of the polyacetylene natural product atractylodemayne A is reported. Stereoselective construction of the conjugated 8(Z),10(E)-diene moiety was achieved through a tethered ring-closing metathesis approach, comprising a Ru-catalyzed RCM followed by a base-induced elimination. A Pd-catalyzed Cadiot-Chodkiewicz coupling was used for the synthesis of the diyne. Overall, atractylodemayne A was synthesized in nine steps for the longest linear sequence.",10.1021/acs.orglett.6b00274,2016-02-17,0.6304794656446567
Journal of Organic Chemistry,Total Synthesis of the <i>Kopsia </i><i>l</i><i>apidilecta </i>Alkaloid (±)-Lapidilectine B,"The total synthesis of Kopsia lapidilecta alkaloid (+/-)-lapidilectine B is described. Notable elements of this synthesis include the first natural products application of the Smalley azido-enolate cyclization to form the 1,2-dihydro-3H-indol-3-one (indoxyl) core and installation of the pyrrolidine ring by a 2-azaallyllithium [3+2] cycloaddition with the acetylene equivalent phenyl vinyl sulfide. Closure of the eight-membered perhydroazocine ring is accomplished via the intramolecular S(N)2 substitution of a mesylate. This constitutes the first synthesis of a member of the 5,6,12,13-tetrahydro-11a,13a-ethano-3H-pyrrolo[1',2':1,8]azocino[5,4-b]indole class of alkaloids.",10.1021/jo048917u,2004-11-13,0.6304764873436124
Journal of the American Chemical Society,Total Synthesis of Ecteinascidin 743,"A straightforward synthesis of ecteinascidin 743 was accomplished from readily available l-glutamic acid as a single chiral source. Our novel synthesis features a concise and convergent approach for construction of the B-ring, consisting of a sequence involving a stereoselective Heck reaction between a diazonium salt and an enamide, oxidative cleavage of the resulting alkene, and intramolecular ortho substitution of the phenol by an aldehyde.",10.1021/ja408034x,2013-09-03,0.6304746052347305
Synlett,A New and Efficient Total Synthesis of (±)-Laurencenone C,"A novel total synthesis of laurencenone C, a chamigrene sesquitepenoid natural product, has been accomplished in 11 steps. In the synthetic sequence, the B-ring of the spirocyclic core was constructed by a one-pot operation involving a Knoevenagel condensation between ethyl cyanoacetate and paraformaldehyde combined with a Diels-Alder reaction of the resulting ethyl 2-cyanoacrylate with isoprene. Moreover, a lithium naphthalenide-induced reductive alkylation of the Diels-Alder adduct was employed to create the C-6 quaternary center and to set the stage for assembling the A-ring.",10.1055/s-0030-1259052,2010-11-17,0.6304725093762814
Synlett,A Convergent and Stereoselective Total Synthesis of Phomolides G and H,"A stereoselective total synthesis of phomolides G and H, a polyketide natural products is described. The synthesis involves organocatalytic enantioselective asymmetric epoxidation, C1-Wittig olefination, and ring-closing metathesis as key steps. The use of organocatalytic MacMillan asymmetric epoxidation for the construction of two chiral centers of phomolides G and H makes this approach more attractive.",10.1055/s-0033-1340348,2014-01-10,0.6304621425481891
Organic Process Research & Development,Preparation of the HIV Attachment Inhibitor BMS-663068. Part 5. Selective C-7 Bromination of the 6-Azaindole Core,"We report research focused on the preparation of an advanced intermediate in the synthesis of a novel antiretroviral. This manuscript describes the development of an efficient oxidation of a 6-azaindole derivative, the bromination of the resulting N -oxide using PyBroP, the removal of the protecting group, and the isolation of the brominated azaindole product. The work reported herein has been successfully implemented in the multikilogram scale to fund development and clinical activities of BMS-663068.",10.1021/acs.oprd.7b00132,2017-08-09,0.6304612199734939
Tetrahedron,Synthesis of chiral Azetidine and its application in asymmetric synthesis,,10.1016/j.tetlet.2025.155617,2025-04-17,0.630453966093021
Organic Letters,Total Synthesis of Ivorenolide A Following a Base-Induced Elimination Protocol,"A concise and stereocontrolled first total synthesis of Ivorenolide A (1) is reported in 16 longest linear steps with a 13.4% overall yield starting from (+)-diethyl tartrate (DET). Key features are base-induced elimination protocol for the construction of chiral propargyl alcohols in both fragments, Pd-catalyzed cross-coupling of terminal acetylenes, and Shiina's 2-methyl-6-nitrobezoic anhydride (MNBA) mediated macrolactonization.",10.1021/acs.orglett.5b00138,2015-01-28,0.6304522444508602
Journal of Organic Chemistry,"Desymmetrization of <i>meso</i> -Anhydride Enabled Enantioselective Synthesis of (−)-7-(Bromomethylene)-3-amidobicyclo[2.2.1]heptane-2-carboxamide, a Scaffold for Divergent Drug Discovery Synthesis","An enantioselective synthesis (>99% ee) of (−)-(1 R, 2 S, 3 R, 4 R,Z )-7-(bromomethylene)- N -(4-fluoro-3-(trifluoromethyl)phenyl)-3-(2,2,2-trifluoroacetamido)bicyclo[2.2.1]heptane-2-carboxamide ((−)- 1 ), a scaffold for divergent drug discovery synthesis, has been developed. The synthesis employed dimethyl(phenyl)silyl moiety as a “masked” hydroxy group and started with an exclusively endo selective Diels–Alder reaction of readily available cyclopenta-2,4-dien-1-yldimethyl(phenyl)silane ( 8 ) with maleic anhydride ( 3 ) to afford the tricyclic anhydride 17 . Desymmetrization of this meso -anhydride 17 was enabled by a high yielding quinidine-mediated opening with benzyl alcohol to generate the benzyl hemiester 4 with >93% ee which was upgraded to greater than 99% ee by chiral resolution with (1 R,2 R )-(−)-1,2-diaminocyclohexane 19 . Other key features of this synthetic route involved a Curtius rearrangement for the formation Teoc-protected amino bicyclo[2.2.1]heptane intermediate 23, a Fleming-Tamao oxidation for the conversion of dimethyl(phenyl)silyl to the hydroxy group and a Swern oxidation of the alcohol 30 to the strained-ring ketone 31 . Finally, the bromo olefin of (−)- 1 was installed by a stereoselective Wittig reaction of 31 using (bromomethyl)triphenylphosphonium bromide.",10.1021/acs.joc.5c02021,2025-12-03,0.6304477963769538
Organic Letters,Stereoselective Total Synthesis of Carolacton,"A short and convergent strategy for the stereoselective total synthesis of biologically active natural product carolacton has been accomplished. Our synthesis highlights the Urpi acetal aldol, Crimmins aldol, Ireland–Claisen rearrangement, TiCl 4 -assisted aldol followed by β-hydroxy elimination to construct C 7 –C 8 olefin, and ring-closing metathesis as the key steps for achieving the target molecule with an overall yield of 18.8%.",10.1021/acs.orglett.7b00903,2017-04-24,0.6304459067672438
Green Chemistry,"The use of environmental metrics to evaluate green chemistry improvements to the synthesis of (S,S)-reboxetine succinate","The Pfizer Green Chemistry metrics program is described and exemplified with a case history involving the synthesis of (S,S)-reboxetine succinate. The initial route used a classical resolution approach and generated high levels of waste. This route was replaced by an enantiospecific synthesis which used Sharpless epoxidation chemistry, an enzymatic process to selectively protect a primary alcohol and a new efficient method of chiral morpholine construction as key steps. These improvements reduced the levels of waste produced by the synthesis by more than 90%. Detailed metrics starting from a common starting material (trans-cinnamyl alcohol) for all routes of synthesis are presented.",10.1039/c1gc15921f,2011-10-31,0.6304428455929137
Journal of Organic Chemistry,An Isomünchnone-Based Method for the Synthesis of Highly Substituted 2(1<i>H</i>)-Pyridones,"1-(Benzenesulfonyl-diazoacetyl)-pyrrolidin-2-one was prepared by a diazo transfer of 1-(benzenesulfonylacetyl)-pyrrolidin-2-one with p- acetamidobenzenesulfonyl azide and triethylamine. Treatment of the diazoimide with a catalytic quantity of rhodium(II) acetate resulted in the formation of an isomünchnone dipole, which underwent bimolecular trapping with various dipolarophiles in high yield. The initially formed cycloadducts were not isolable or observed, as they all readily underwent ring opening to give the 3-hydroxy-2(1 H )-pyridone ring system. The 3-hydroxy-2(1 H )-pyridones were readily converted to the corresponding triflates, which function as suitable substrates in various types of palladium-catalyzed cross-coupling reactions. Commercial tetrakis(triphenylphoshine)palladium was found to be a particularly effective catalyst for the cross-coupling with aryl, vinyl, and acetylenic partners. An application of the method to the synthesis of the indolizidine alkaloid (±)-ipalbidine was carried out in eight steps in 17% overall yield. The angiotensin-converting enzyme inhibitor (−)-A58365A was also synthesized by a process based on the [3 + 2]-cycloaddition reaction of a phenylsulfonyl substituted isomünchnone intermediate. The starting material for this process was prepared from l -pyroglutamic acid and involved using a diazo phenylsulfonyl substituted pyrrolidine imide. Treatment of the diazoimide with Rh 2 (OAc) 4 in the presence of methyl vinyl ketone afforded a 3-hydroxy-2-pyridone derivative, which was subsequently converted to the ACE inhibitor in six additional steps.",10.1021/jo9911600,1999-10-22,0.6304383476259083
Journal of Organic Chemistry,Chirospecific Syntheses of Conformationally Constrained 7-Azabicycloheptane Amino Acids by Transannular Alkylation,"A new method is reported for the chirospecific preparation of optically pure 1-carboxy-7-azabicycloheptane amino acids for the generation of peptidomimetics as conformational probes. The method allows for the multigram preparation of these amino acid analogues through use of a thiolactam sulfide contraction and a transannular alkylation sequence as the key C-C bond-forming steps, starting from L-glutamic acid. The route provides access to two common intermediates, 7-(benzyloxycarbonyl)-1-carboxy-7-azabicyclo[2.2.1]-3-heptane and (1S,4R)-7-(benzyloxycarbonyl)-1-carboxy-7-azabicyclo[2.2.1]-3-heptanone tert-butyl ester, for elaboration to symmetrical and chiral amino acid homologues, respectively. Decarboxylation of the C-1 carboxy unit of the latter intermediate also demonstrated the applicability of the method for a short, chirospecific preparation of a (+)-epibatidine intermediate, (1S,4R)-7-(tert-butyloxycarbonyl)-1-carboxy-7-azabicyclo[2.2.1]-3-heptanone.",10.1021/jo960759m,1996-01-01,0.630411981430796
Synthesis,Efficient Synthesis of (<i>E</i>)-9-Chloro-4-methyl-8-oxo-4-nonenoic Acid from 4-Chloro-2-methyl-2-butene,"All articles of this category ( E )-9-Chloro-4-methyl-8-oxo-4-nonenoic acid, a useful intermediate in the synthesis of the potent antigestational agent ORF-13811 (a 3,8-dioxabicyclo[3.2.1]octane derivative), is efficiently prepared from 4-Choro-2-methyl-2-butene by using the ortho ester Claisen rearrangement.",10.1055/s-1991-26556,1991-01-01,0.630391586852756
Tetrahedron,"A facile synthesis of (S)-gizzerosine, a potent agonist of the histamine H2-receptor",,10.1016/j.tetlet.2007.09.165,2007-10-02,0.630382319468875
Journal of the American Chemical Society,Total synthesis of (.+-.)-aspirochlorine,"Aspirochlorine is a unique epidithiodioxopiperazine isolated from Aspergillus oryzae, Asp. tamarii and Asp. flavus. The molecule contains a highly unusual bicyclo [3.2.2]disulfide ring system which has previously never been prepared. The first total synthesis of (±)-Aspirochlorine was achieved from commercially available 5-chlororesorcinol 324 in 16 steps. The key step in the synthesis was an efficient intramolecular cycloaddition reaction of hydroxamic ester 344 to form the parent spiro [benzofuran-2(3H),2'-piperazine] ring system 345 as a single stereoisomer. In addition the synthesis employed a 2-nitrobenzyl moiety as a novel amide protecting group. The 2-nitrobenzyl group could be removed in 72% yield under photolytic conditions. Synthetic aspirochlorine was identical to natural material in comparison by 1H NMR, IR and HPLC. Comparison of the biological activity of aspirochlorine versus other epidithiodioxopiperazines was investigated as a function of superoxide production. Although aspirochlorine was shown to be capable of producing superoxide as evidenced in DNA plasmid nicking and NBT reduction assays, the observed activity was less than the 6-membered epidithiodioxopiperazines.",10.1021/ja00055a025,1993-01-01,0.6303809388733643
Organic Letters,"A Flexible Route to (5<i>R</i>)-Thiolactomycin, a Naturally Occurring Inhibitor of Fatty Acid Synthesis",[formula: see text] A new and efficient asymmetric synthesis of naturally occurring (5R)-thiolactomycin (1) using D-alanine as the source of chirality is described.,10.1021/ol026685k,2002-10-01,0.6303602778313401
Tetrahedron,Synthesis of the CD ring in taxol from (S)-(+)-carvone,,10.1016/s0040-4039(01)01802-0,2001-11-01,0.6303533321522474
Tetrahedron,"Ring expansion of 2-chloromethylbenzothiazole: Synthesis of heteroarylalkylidene 1,4-benzothiazines",,10.1016/0040-4039(95)00111-o,1995-03-01,0.6303533321522474
Tetrahedron,Synthesis of the AB ring system of gambierol,,10.1016/s0040-4039(98)01310-0,1998-08-01,0.6303533321522474
Tetrahedron,"The first synthesis of the benzo[b]indolo[1,2-h][1,7]naphthyridine ring system",,10.1016/j.tetlet.2011.02.106,2011-03-07,0.6303533321522474
Tetrahedron,A synthesis of the ring system of terpestacin,,10.1016/s0040-4039(98)02535-0,1999-01-01,0.6303533321522474
Tetrahedron,The synthesis of the CD ring of paclitaxel,,10.1016/s0040-4039(01)01653-7,2001-10-01,0.6303533321522474
Tetrahedron,Synthesis of STU ring of maitotoxin,,10.1016/j.tetlet.2025.155799,2025-08-22,0.6303533321522474
Tetrahedron,Porphyrin synthesis by ring transplantation,,10.1016/s0040-4039(00)98256-x,1985-01-01,0.6303533321522474
Tetrahedron,Synthesis of the ravidomycin ring system,,10.1016/s0040-4039(00)96148-3,1987-01-01,0.6303533321522474
Tetrahedron,"Synthesis of the octahydro-8b-azaacenaphthylene ring system, a portion of the dimeric coccinellid alkaloids",,10.1016/s0040-4039(96)02348-9,1997-01-01,0.6303533321522474
Tetrahedron,Synthesis of the E ring of gambierol,,10.1016/s0040-4039(98)01311-2,1998-08-01,0.6303533321522474
Tetrahedron,A Synthesis of A-Ring Synthons for Dihydrotachysterols,,10.1016/s0040-4039(00)91693-9,1992-03-01,0.6303533321522474
Tetrahedron,Synthesis of the H ring of gambierol,,10.1016/s0040-4039(98)01312-4,1998-08-01,0.6303533321522474
Tetrahedron,[3.2]Metacyclophanes: synthesis and ring inversion,,10.1016/s0040-4039(00)70388-1,1964-01-01,0.6303533321522474
Tetrahedron,The first synthesis of an A-ring fused steroidal isothiazole,,10.1016/s0040-4039(00)73456-3,1994-09-01,0.6303533321522474
Tetrahedron,Iterative synthesis of the ABCDEF-ring system of yessotoxin and adriatoxin,,10.1016/s0040-4039(03)00252-1,2003-03-01,0.6303533321522474
Tetrahedron,"An unequivocal synthesis of the ring-A,B dihydropyrromethenone of phytochrome",,10.1016/0040-4039(95)00032-8,1995-02-01,0.6303533321522474
Tetrahedron,Synthesis of ring-a-norgibberellins,,10.1016/s0040-4039(01)86064-0,1979-01-01,0.6303533321522474
Tetrahedron,Synthesis of the trinervitane ring system,,10.1016/s0040-4039(98)01469-5,1998-09-01,0.6303533321522474
Tetrahedron,"Synthesis of the tricyclo[9.3.1.03,8]pentadecane (ABC) ring system of taxane diterpenes",,10.1016/s0040-4039(00)76878-x,1994-05-01,0.6303533321522474
Tetrahedron,Stereocontrolled synthesis of the IJK ring segment of yessotoxin,,10.1016/j.tetlet.2006.07.027,2006-08-02,0.6303533321522474
Tetrahedron,Stereocontrolled synthesis of the histrionicotoxin ring system,,10.1016/s0040-4039(00)89277-1,1985-01-01,0.6303533321522474
Tetrahedron,"Ring expansion by sulphur migration: Synthesis of 2-alkylidene-1,4-benzodithians and 1,4-benzodithiins",,10.1016/s0040-4039(01)91533-3,1978-01-01,0.6303533321522474
Tetrahedron,Synthesis of the a-ring diols and diolepoxides of benz[a]anthracene,,10.1016/s0040-4039(01)83773-4,1977-01-01,0.6303533321522474
Synthesis,Stereoselective Synthesis of a Highly Oxygenated δ-Lactone Related to the Core Structure of (–)-Enterocin,"The title compound was prepared in a concise route starting from an appropriately protected ( S )-glyceraldehyde. A highly diastereoselective (d.r. >95:5) Mukaiyama aldol reaction of an acetoacetate-derived silyl enol ether served as the initial step of the synthetic sequence. It was found that protection of the glyceraldehyde as a butane-2,3-dione acetal is required to achieve the desired diastereoselectivity. Upon lactonization, a Tsuji–Trost allylation and a subsequent one-pot reaction cascade including an ozonolysis and an α-hydroxylation gave dia­stereoselective access to the desired α-hydroxy-β-oxo-δ-lactone. Alternative synthetic approaches are discussed and proof for the configuration of the product is presented.",10.1055/s-0035-1562539,2016-09-09,0.630347943902966
Organic Letters,"Iridium-Catalyzed Asymmetric Hydrogenation of α-Substituted α,β-Unsaturated Acyclic Ketones: Enantioselective Total Synthesis of (−)-Mesembrine","A highly efficient asymmetric hydrogenation of α-substituted α,β-unsaturated acyclic ketones catalyzed by chiral spiro iridium complexes for the preparation of chiral 2-substituted allylic alcohols has been developed (ee up to 99.7%). This method provides a concise route to (-)-mesembrine (34% yield, 12 steps).",10.1021/ol302842h,2012-12-04,0.6303435652219942
Synlett,First Synthesis of Metallated Titanacyclopropenes,All articles of this category A novel and efficient one-pot synthesis of tris metallated olefins is described by using the di iso propyloxy( η 2 -propene)titanium derivative. metallated titanacyclopropenes - titanium(II) - bismetallic - alkynes - alkenes,10.1055/s-1999-2964,1999-12-01,0.6303411494996961
Angewandte Chemie International Edition,Total Synthesis of the Ubiquitin‐Activating Enzyme Inhibitor (+)‐Panepophenanthrin,The [4+2] dimerization of epoxyquinol 1 is rendered irreversible by formation of a hemiacetal in the enantioselective total synthesis of the ubiquitin-activating enzyme inhibitor (+)-panepophenanthrin (2).,10.1002/anie.200351862,2003-08-22,0.6303057403645574
Journal of Organic Chemistry,Efficient Asymmetric Synthesis of <i>abeo-</i>Abietane-Type Diterpenoids by Using the Intramolecular Heck Reaction,"The synthesis of the abeo-abietane-type diterpenoids, i.e., (-)-dichroanal B, (-)-dichroanone, and taiwaniaquinone H, was achieved by using the intramolecular asymmetric Heck reaction. Our synthetic routes required fewer steps and gave a much higher overall yield and ee within shorter steps than those for racemic and antipodal forms reported to date (10, 12, and 13 steps with an overall yield of 50%, 40%, and 39%, and 94%, 98%, and 98% ee, respectively).",10.1021/jo901972b,2009-12-07,0.6302964627903883
Tetrahedron,Studies on the total synthesis of sesbanimide: A highly diastereoselective synthesis of the ab ring system,,10.1016/s0040-4039(00)84794-2,1986-01-01,0.6302924450693953
Angewandte Chemie International Edition,Total Synthesis of Ouabagenin and Ouabain,"The highly oxygenated steroid ouabagenin (1 b) and its glycoside ouabain (1 a) were prepared by a strategy based on a polyanionic cyclization. Starting building blocks A and B were combined to give the key intermediate C and transformed into 1 b in 27 steps. Finally, ouabagenin (1 b) was converted into ouabain (1 a) in six steps (see scheme).",10.1002/anie.200704959,2008-01-08,0.6302780159609352
Journal of Organic Chemistry,Asymmetric Total Synthesis of Lancifodilactone G Acetate. 2. Final Phase and Completion of the Total Synthesis,"The asymmetric total synthesis of lancifodilactone G acetate was accomplished in 28 steps. The key steps in this synthesis include (i) an asymmetric Diels-Alder reaction for formation of the scaffold of the BC ring; (ii) an intramolecular ring-closing metathesis reaction for the formation of the trisubstituted cyclooctene using a Hoveyda-Grubbs II catalyst; (iii) an intramolecular Pauson-Khand reaction for construction of the sterically congested F ring; (iv) sequential cross-metathesis, hydrogenation, and lactonization reactions for installation of the anomerically stabilized bis-spiro ketal fragment of lancifodilactone G; and (v) a Dieckmann-type condensation reaction for installation of the A ring. The strategy and chemistry developed for the total synthesis will be useful in the synthesis of other natural products and complex molecules.",10.1021/acs.joc.7b02917,2018-03-06,0.630270351598695
Tetrahedron,β-Keto ester aminolysis of pheophorbide a methyl ester: a facile route for asymmetric chlorin ring substitution,,10.1016/j.tetlet.2009.11.121,2009-12-03,0.630265257914046
Tetrahedron,Bromination of barbaralone; a new route to triasteranes,,10.1016/s0040-4039(01)88880-8,1969-01-01,0.6302565901258907
Organic Letters,"Stereoselective Synthesis of 1,4,5-Tri-<i>cis</i>-guaiane Sesquiterpene: First Total Synthesis of (−)-Dendroside C Aglycon","The first total synthesis of (-)-dendroside C aglycon, consisting of a 1,4,5-tri-cis-guaiane skeleton, from a versatile hydroazulene intermediate has been accomplished. The key features of the syntheses include the stereoselective preparation of the unusual cis-hydroazulene core via a sequence of a unique Dieckmann condensation of the bicyclic lactone system, which was concisely prepared by the tandem conjugate addition and intramolecular allylic alkylation of a butenolide precursor, and construction of the characteristic tricyclic skeleton by a carbene-mediated cyclopropanation.",10.1021/acs.orglett.7b03701,2018-01-16,0.6302488975978184
Organic Process Research & Development,Practical Process for synthesizing<i>R</i>-Tetrahydropapaverine─A Key Intermediate of Cisatracurium Besylate (Nimbex),"In this paper, a practical process to synthesize the key intermediate R -tetrahydropapaverine of cisatracurium besylate was proposed. First, tetrahydropapaverine hydrochloride ( 1 .HCl) was prepared from inexpensive and commercially available 2-(3,4-dimethoxyphenyl)ethanamine ( 2 ) and 3,4-dimethoxybenzeneacetic acid ( 3 ) through a one-pot process. The yield and purity of the product were up to 85.4 and 98.1% on a 150 g scale, respectively. Then, a new resolution process was developed to prepare R -tetrahydropapaverine by using a half equivalent of N -acetyl- d -phenylalanine, and the obtained R -tetrahydropapaverine had a yield of 28.1% and 98.0% ee on a 120 g scale. Furthermore, the S -isomer was racemized to 1 .HCl in the one-pot process with 77.7% isolated yield and 99.0% purity.",10.1021/acs.oprd.2c00243,2022-11-09,0.6302466969396012
Journal of Organic Chemistry,Total Synthesis of the Tropoloisoquinoline Alkaloid Pareitropone via Alkynyliodonium Salt Chemistry and Related Studies,"The first chemical synthesis of pareitropone, by a route featuring application of alkynyliodonium salt chemistry, is described. The key transform initiates with addition of an alkylidenecarbene, derived by intramolecular nucleophile addition to the alkynyliodonium moiety, to a proximal aromatic ring. This addition delivers a highly strained norcaradiene substructure that rapidly reorganizes to furnish the pareitropone skeleton.",10.1021/jo026337w,2002-11-01,0.6302323125266796
Organic Letters,Development of a One-Step Synthesis of oxa-Spirocyclic Diphosphine Ligands Driven by Their Application in the Industrial Synthesis of Sacubitril,"Herein we have developed a highly practical and efficient one-step coupling protocol for the synthesis of chiral spiro diphosphine ligands, especially for the oxa -spiro diphosphine ligands O -SDP, which showed excellent reactivity and diastereoselectivity in the asymmetric hydrogenation of a key intermediate of Sacubitril. It should be noted that the one-step coupling protocol could be operated on a kilogram scale, and the resulting ruthenium catalyst of O -SDP could hydrogenate the key intermediate of Sacubitril on an industrial scale.",10.1021/acs.orglett.3c03536,2024-01-16,0.6302287877761061
Organic Letters,"Synthesis of 4,4-Dimethyl-1,6-heptadiyne and Alcyopterosin O","A four-step synthesis of 4,4-dimethyl-1,6-heptadiyne and an associated five-step synthesis of alcyopterosin O, an illudalane sesquiterpene natural product, are described starting from commercially available dimedone. The process features C-C bond-cleaving fragmentation and elimination methods for making alkynes, and it proceeds by way of nonsymmetrical diynes that are themselves valuable synthetic building blocks, as exemplified by the synthesis of alcyopterosin O.",10.1021/acs.orglett.0c03356,2020-11-04,0.6302273436192748
Organic Process Research & Development,"Development of an Asymmetric Hydrogenation Route to (<i>S</i>)-<i>N</i>-Boc-2,6-dimethyltyrosine","An improved, simpler and potentially more economical route to ( S )- N -Boc-2,6-dimethyltyrosine 1, based on a previously published route, is presented. Key modifications were to prepare the dehydroaminoacid hydrogenation substrate 6 in a one-pot process directly from serine methyl ester and 4-iodo-3,5-dimethylphenyl acetate 4 and to identify a significantly more active asymmetric hydrogenation catalyst that allowed a 5-fold reduction in catalyst loading.",10.1021/op200065p,2011-05-26,0.6302177315517166
Synthesis,"Synthesis of a 2,5-Diazabicyclo[2.2.1]heptane-Derived α,β-Diamino Acid","The synthesis of optically pure (1 S ,4 S )-2,5-diazabicyclo[2.2.1]heptane-1-carboxylic acid starting from easily available ‘chiral pool’ l -4-hydroxyproline is reported. A tandem Strecker reaction–intramolecular nucleophilic cyclization (STRINC) sequence was used as the key synthetic step for the first time to prepare a diamino acid. Careful examination of the side products obtained in the STRINC step allowed the suggestion of a mechanistic explanation for the observed facts and optimization the yield of the aminonitrile precursor. The reported scalable synthesis opens the way to use the diamino acid as a branch point in peptides and as a building block in drug discovery.",10.1055/s-0034-1380116,2015-02-03,0.6302147602538313
Organic Letters,Control of Olefin Geometry in the Bryostatin B-Ring through Exploitation of a <i>C</i><sub>2</sub>-Symmetry Breaking Tactic and a Smith−Tietze Coupling Reaction,"A completely stereocontrolled asymmetric synthesis of an advanced B-ring synthon for the bryostatin family of antitumor agents is reported. Noteworthy features of our synthesis include the Smith-Tietze bis-alkylation reaction between 12 and 13 en route to C(2)-symmetrical ketone 10 and the totally stereoselective conversion of 10 into triol 18 via a Grignard addition tactic. Triol 18 was converted to epoxide 3 in nine steps, and an acid-catalyzed intramolecular Williamson etherification reaction completed the synthesis of 2.",10.1021/ol005850y,2000-06-24,0.6302105864191301
Tetrahedron,The use of zinc enolates in the synthesis of a key intermediate for the preparation of trinem antibiotics,,10.1016/0040-4039(96)01606-1,1996-10-01,0.6302007911398952
Journal of the American Chemical Society,Total Synthesis of (−)-Principinol C,"We have achieved the first total synthesis of (-)-principinol C, which possesses an intriguing and complex 5/7/6/5 tetracyclic skeleton with eight contiguous stereocenters. The 5/7/6/5 tetracyclic skeleton of principinol C was assembled using an intramolecular Pauson-Khand reaction as the key step. This synthetic route represents the first application of the intramolecular Pauson-Khand reaction of enyne to construct the 7,5-bicyclic ring system in natural product synthesis.",10.1021/jacs.2c08694,2022-10-24,0.6301965607067044
Tetrahedron,Comments on the papers “the synthesis of samane (desoxysamanine) and 17ß-hydroxy-samane” and “the total synthesis of samanine”,,10.1016/s0040-4039(01)88520-8,1969-01-01,0.6301912560981181
Synthesis,"Synthesis of a New Pyrido[3,2-b]carbazole as an Ellipticine-Makaluvamine Hybrid","The first synthesis of pyrido[3,2-b]carbazole as an ellipticine-makaluvamine hybrid in 13 steps and 2% overall yield from commercially available 2,5-dimethoxyaniline is described.",10.1055/s-0030-1260015,2011-04-19,0.630189432216807
Journal of Organic Chemistry,Stereocontrolled Synthesis of <i>ent</i>-Grindelic Acid. A Useful Example of Diastereofacial Guidance in an Oxonium Ion-Initiated Pinacolic Ring Expansion,"An enantioselective synthesis of (+)-grindelic acid is described, confirming that the dextrorotatory enantiomer is antipodal to the natural diterpenoid. The optically pure bicyclic ketone 5 representing the AB ring system is constructed from the levorotatory Wieland−Miescher ketone and must therefore possess the absolute configuration shown. Coupling of 5 with the 5-lithio derivative of optically active 2,3-dihydrofuran 3 derived from ( R )-(−)-linalool was effected for the purpose of realizing acid-catalyzed rearrangement with generation of the appropriate spirocyclic framework. This key step is highly stereocontrolled, leading predominantly to 7 . Once the advanced intermediate 15 is available in this fashion, its subsequent exposure to oxidation and dehydration steps led to the target molecule. The synthesis demonstrates unequivocally that natural (−)-grindelic acid is a true labdane diterpenoid.",10.1021/jo960547p,1996-01-01,0.6301832122455773
Tetrahedron,"Short step synthesis of (22E, 24R)-5α-ergosta-2,22-dien-6-one, a key intermediate for the preparation of 24-epibrassinolide",,10.1016/s0040-4039(00)97512-9,1990-01-01,0.6301344900983933
Journal of Organic Chemistry,"Asymmetric Hydroformylation-Initiated Tandem Sequences for Syntheses of (+)-Patulolide C, (−)-Pyrenophorol, (+)-Decarestrictine L, and (+)-Prelog Djerassi Lactone","Four different Rh-catalyzed asymmetric hydroformylation (AHF) tandem reactions have been developed in the context of the total syntheses of (+)-patulolide C, (-)-pyrenophorol, (+)-decarestrictine L, and (+)-Prelog-Djerassi lactone. A total synthesis of (+)-patulolide C has been accomplished in three steps utilizing a Rh(I)-catalyzed Z-selective anti-Markovnikov hydroacetoxylation of a known alkyne to give a Z-enol acetate with excellent selectivity. An AHF/intramolecular Wittig olefination cascade was utilized to set the C4-hydroxyl stereochemistry, E-olefin geometry, and form the macrolactone. In addition, both (-)-pyrenophorol and (+)-decarestrictine L have been synthesized from the enantiomeric (4R)- and (4S)-4-(tert-butyldimethylsiloxy)-1-pentyne in five and four steps, respectively. These syntheses feature Ru(II)-catalyzed Z-selective anti-Markovnikov hydroacetoxylation of terminal alkynes followed by AHF/Wittig olefination sequences to rapidly establish functionality and stereogenicity. A synthesis of (+)-Prelog-Djerassi lactone was accomplished in three isolations from the known 1-vinyl-4-methyl-2,6,7-trioxabicyclo[2.2.2]octane ortho ester. An AHF/crotylation tandem sequence has been developed to set the C2-C4 stereochemistry. An asymmetric hydrogenation was employed to set the C6 stereochemistry, resulting in an especially efficient enantioselective synthesis from achiral starting material. In summary, these syntheses have greatly improved efficiency in terms of atom-economy, catalytic stereoselective transformations, inexpensive reagents, step-counts, and overall yield when compared with previous synthetic attempts.",10.1021/jo502301k,2014-11-14,0.6301325990948962
Organic Letters,Function-Oriented Synthesis:  Studies Aimed at the Synthesis and Mode of Action of 1α-Alkyldaphnane Analogues,[reaction: see text] An efficient synthetic route to the ABC tricyclic core of 1alpha-alkyldaphnanes has been developed. The conformational bias imparted by the C6-C9 oxo-bridge of BC-ring system 12 was used to elaborate the ABC-ring system precursor including the introduction of the beta-C5 hydroxyl group. A completely diastereoselective palladium-catalyzed enyne cyclization was then employed to establish the A-ring with a C1 appendage.,10.1021/ol0705649,2007-04-01,0.6301302474763416
Tetrahedron,"Studies on the Synthesis of Strychnos Indole Alkaloids. An Efficient Stereocontrolled Synthetic Route to 2,4,8- and 2,8,9-Trisubstituted 2-Azabicyclo[3.3.1]nonan-7-ones",,10.1016/0040-4039(92)88140-z,1992-04-01,0.6301272516924856
Organic Letters,First Total Synthesis of the Proposed Structure of Batatin VI,"The first total synthesis of batatin VI, an architecturally novel resin glycoside dimer, has been achieved via a convergent [5 + 3] glycosidic coupling approach. An improved protocol for the construction of the key 18-membered macrolactone core using a Keck macrolactonization method was introduced. However, the synthesized compound was not identical to the natural batatin VI.",10.1021/ol4020255,2013-07-30,0.6301191969335254
Journal of Organic Chemistry,Enantiospecific Total Synthesis of Lairdinol A,"The synthesis of lairdinol A, a component of the host-selective phytotoxin depsilairdin, was achieved in 12 steps (18% overall yield) without the use of protecting groups starting with the Diels-Alder reaction of (R)-carvone with 3-trimethylsilyloxy-1,3-pentadiene. The key step established the trans ring fusion by preferential epoxidation of a trans-fused enone in an equilibrating mixture of the cis-fused and trans-fused diastereomers (i.e., equivalent to a dynamic kinetic resolution of these isomers). The synthesis confirms the absolute configurations of lairdinol A and its enantiomer, cyperusol C.",10.1021/jo7024465,2008-01-08,0.6301108343113202
Synlett,Total Synthesis of New Lipocarbazoles Isolated from the Actinomycete Tsukamurella pseudospumae Acta 1857¹,New lipocarbazoles were synthesized by a sequence of three palladium-mediated coupling reactions and an improved protecting group strategy.,10.1055/s-0029-1217815,2009-08-17,0.6300994951890169
Organic Process Research & Development,Process Research on the Asymmetric Hydrogenation of a Benzophenone for Developing the Manufacturing Process of the Squalene Synthase Inhibitor TAK-475,"A practical synthetic method for the synthesis of the chiral benzhydrol 8, which is the key intermediate of the squalene synthase inhibitor TAK-475 ( 1 ), has been developed. The method, via asymmetric hydrogenation of the benzophenone 7, employed Noyori’s ruthenium precatalyst of the type [RuCl 2 (diphosphine)(diamine)]. We focused on tuning of the chiral diphosphine, and have discovered a novel ligand, DADMP-BINAP ( 18c ), for the catalyst that has allowed reduction of the operating pressure in the asymmetric hydrogenation. The precatalyst containing 18c performed effectively at low hydrogen pressure (<1 MPa) with sufficient enantioselectivity, and the result enabled us to successfully obtain enantiomerically pure 8 on a multikilogram scale.",10.1021/op2001673,2011-08-03,0.6300964869471528
Tetrahedron,Stereoselective synthesis of HR 780 a new highly potent HMG-CoA reductase inhibitor,,10.1016/0040-4039(90)80121-2,1990-01-01,0.6300927637036843
Tetrahedron,"A new and facile route for the synthesis of chiral 1,2-diamines and 2,3-diamino acids",,10.1016/j.tetlet.2004.11.088,2004-12-12,0.6300895536092624
Journal of Organic Chemistry,Total Synthesis of Kanamienamide,"Kanamienamide is a novel enol ether containing enamide with a single digit micromolar inhibitory activity against cancer cell lines. An efficient and convergent total synthesis of kanamienamide has been developed for the first time, which features a Cu-mediated amide coupling with vinyl iodide at the late stage. Other key transformations include Evans asymmetric alkylation, CBS asymmetric reduction, ring-closing metathesis reaction, and Stork-Zhao-Wittig olefination. This strategy is amenable for facile analogue preparation and SAR studies.",10.1021/acs.joc.7b01984,2017-09-25,0.630068147208596
Organic Process Research & Development,Synthesis of Methyl 3-Hydroxyisoxazole-5-Carboxylate Via Bromination of Dimethyl Fumarate under Photoflow Conditions and Its Safe Homologation into 3-(3-Methoxyisoxazol-5-yl) Propanoic Acid,"The route scouting and development activities toward a safe and scalable manufacturing route for 3-(3-methoxyisoxazole-5-yl) propanoic acid are outlined in this article. In a first step, methyl 3-hydroxy-5-isoxazolecarboxylate (CAS: 10068-07-2) was prepared on a kilogram scale via bromination of dimethyl fumarate under photoflow conditions followed by condensation with hydroxyurea. This intermediate was then two-carbon homologated by a sequence of ester reduction, chlorination, and nucleophilic substitution with commercially available triethylmethanetricarboxylate. Subsequently, a double decarboxylation event unveiled the desired building block 3-(3-methoxyisoxazole-5-yl) propanoic acid. During our development activities, a preliminary safety assessment of the intermediates by differential scanning calorimetry revealed that a high thermal decomposition energy was recorded for the isoxazole heterocycle. Therefore, our route scouting activities and isolation strategies needed to be carefully assessed under the guidance of the Oxygen balance/Rule of 6/Explosive functional group/Onset temperature/Scale (OREOS) safety assessment. Finally, to highlight our development activities, a kg-scale campaign demonstrated the scalability of the new route.",10.1021/acs.oprd.3c00334,2024-01-22,0.630066603851553
Tetrahedron,A general synthetic approach for the synthesis of β-hydroxy-δ-lactones: asymmetric total synthesis of prelactones and epi-prelactones V and E,,10.1016/j.tetlet.2007.11.080,2007-11-20,0.6300643047853848
Tetrahedron,"Synthesis of threo- and erythro-bis(2,2′-tetrahydrofuran). A novel serendipitous synthesis of a spiroketal",,10.1016/s0040-4039(99)00173-2,1999-03-01,0.6300610108362136
Journal of Organic Chemistry,Formal Total Synthesis of Hybocarpone Enabled by Visible-Light-Promoted Benzannulation,"The formal total synthesis of hybocarpone was achieved in eight steps from commercially available 1,2,4-trimethoxybenzene. Key transformations include a visible-light-promoted benzannulation to construct the key α-naphthol intermediate and a modified CAN-mediated dimerization/hydration cascade sequence to generate the vicinal all-carbon quaternary centers in a stereocontrolled manner. The total synthesis of boryquinone was also achieved in seven steps.",10.1021/acs.joc.8b02595,2018-11-28,0.6300524130560194
European Journal of Organic Chemistry,Total Synthesis of Calothrixin B and Its Analogs,Abstract The total synthesis of calothrixin B and its analogs was achieved starting from 2‐methylindole. The synthesis involved an electrocyclization of 2‐nitroarylvinyl‐3‐phenylsulfonylvinylindoles as a key step to give 2‐nitroaryl‐4‐methoxy‐3‐methylcarbazoles. Oxidation of these compounds followed by reductive cyclization led to N ‐phenylsulfonylquinocarbazoles. These quinocarbazoles underwent hydrolysis and aerial oxidation in one pot to give the target compounds.,10.1002/ejoc.201301524,2013-12-12,0.6300421108040573
Synlett,A Concise Synthesis of 3-Hydroxy-4-(β-glucopyranosyl) Benzoate: A New Route to β-<i>C</i>-Aryl Glycosides,All articles of this category annulation - cyclization - carbohydrates - glycosides - phenols,10.1055/s-1999-3165,1999-08-01,0.630039360250374
Chemical Science,"Short, enantioselective, gram-scale synthesis of (−)-zephyranthine","A reasonable synthesis design by strategically integrating functional group manipulation into the ring system construction resulted in a short, enantioselective, gram-scale total synthesis of (-)-zephyranthine. The concise route includes a catalytic Michael/Michael cascade for the asymmetric synthesis of a penta-substituted cyclohexane with three contiguous stereogenic centers, a remarkable 8-step one-pot operation to easily assemble the zephyranthine tetracyclic skeleton, the regioselective construction of a double bond in the C ring and an asymmetric dihydroxylation. This synthesis is also flexible and paves a potential path to a variety of cyclohexylamine-fused tricyclic or polycyclic alkaloids.",10.1039/d1sc03147c,2021-01-01,0.6300261139931292
Organic Process Research & Development,Large-Scale Synthesis of Eldecalcitol,"Industrial-scale synthesis of eldecalcitol is described. AA highly diastereoselective epoxidation of p -methoxybenzyl (PMB) protected dienol at room temperature provides the key epoxide intermediate with a secondary hydroxyl group, which is alkylated with a triflate to set up all of the subunits at the C-1, C-2, and C-3 positions of the A-ring fragment. Selective protecting group manipulation followed by palladium-catalyzed cyclization then provides the A-ring synthon. The C/D-ring fragment is obtained by (1) direct C-H hydroxylation of Grundman’s ketone using in situ prepared trifluoropropanone dioxirane and (2) protection. Finally, the coupling of the A-ring with the C/D-ring fragment, global deprotection, and recrystallization provide the highly crystalline eldecalcitol.",10.1021/acs.oprd.0c00436,2020-12-17,0.6300151458921879
Angewandte Chemie International Edition,A Concise Flow Synthesis of Efavirenz,"Efavirenz is an essential medicine for the treatment of HIV, which is still inaccessible to millions of people worldwide. A novel, semi-continuous process provides rac-Efavirenz with an overall yield of 45%. This streamlined proof-of-principle synthesis relies on the efficient copper-catalyzed formation of an aryl isocyanate and a subsequent intramolecular cyclization to install the carbamate core of Efavirenz in one step. The three-step method represents the shortest synthesis of this life-saving drug to date.",10.1002/anie.201411728,2015-02-27,0.6300019631014503
European Journal of Organic Chemistry,"Scalable Synthesis of Both Enantiomers of Vigabatrin, an Antiepileptic Drug",Vigabatrin is a potent inhibitor of gamma‐aminobutyric acid (GABA) catabolism used for the treatment of epilepsy. Here we have synthesized both enantiomers of the drug vigabatrin in five steps from known intermediates using Wittig olefination and pyrolytic elimination as key steps. The target compounds are synthesized in gram scale amounts with &gt;98 % enantiopurity.,10.1002/ejoc.201801617,2018-11-23,0.6300008529184343
Synlett,Diastereoselective Total Synthesis of Sibirine via Functionalized Imine Precursors,"All articles of this category The spirocyclic alkaloid (±)-sibirine was prepared in a straightforward way from an easily accessible imine precursor. A stabase-mediated alkylation and cyclization process provided an azaspirocyclic intermediate, which was converted stereoselectively to (±)-sibirine via a convenient four step sequence including a stereoselective cerium-catalyzed reduction. The first two steps of this sequence also constitute a formal synthesis of (±)-nitramine.",10.1055/s-1994-22830,1994-01-01,0.6299949420127023
Organic Letters,An Asymmetric Total Synthesis of Brevisamide,"An enantioselective synthesis of marine alkaloid brevisamide was accomplished in a convergent manner. The synthesis utilized an enantioselective hetero-Diels-Alder reaction which sets three chiral centers in compound 11. The synthesis also features a modified Wolff-Kishner reduction, Rubottom oxidation, and Suzuki-Miyaura coupling to furnish brevisamide.",10.1021/ol901691d,2009-08-20,0.6299834513305723
European Journal of Organic Chemistry,Liposidomycins − Synthetic Studies Towards the Ribosyldiazepanone Moiety,"A synthesis of the enantiopure 2-ribosyl-1,4-diazepan-3-one core of liposidomycins, a class of complex lipid nucleoside antibiotics, according to a flexible asymmetric synthesis strategy is described. It involves two building blocks, an enantiopure α-azido-β,γ-epoxybutanol readily available from L-ascorbic acid, and an α-ribosylamino acid obtained from D-ribose. Subsequent cyclization by regiospecific nucleophilic opening of the epoxide by the amino acid followed by peptidic coupling affords the target ribosyl diazepanone.",10.1002/1099-0690(200108)2001:16<3089::aid-ejoc3089>3.0.co;2-l,2001-08-01,0.6299832456218999
Synthesis,"Diastereo- and Enantioselective Formal Synthesis of (+)-Conagenin via Asymmetric [2,3]-Wittig Rearrangement","All articles of this category The formal synthesis of the immunomodulator (+)-conagenin ( 1 ) is accomplished in a twelve-step sequence with good overall yield (19%), diastereoselectivity and enantiomeric excess (ds syn = 88%, ee = 91%). Key steps of the synthesis are the asymmetric [2,3]-Wittig rearrangement of crotyloxyacetaldehyde-SAEP-hydrazone ( S )- 5 and the diastereoselective reduction of methylketone ( R , S )- 12 . The absolute configuration of the (4 R )-stereogenic center was determined by 1 H NMR NOE-measurements with respect to the known absolute configuration of the (2 R ,3 S )-stereogenic centers of lactone ( R , S , R )- 14 . conagenin - immunomodulator - [2,3]-Wittig rearrangement - chiral hydrazone - asymmetric synthesis",10.1055/s-1999-3398,1999-02-01,0.6299781422810715
Tetrahedron,"A simple enantioselective synthesis of (R)- and (S)-1,7-dioxaspiro[5.5]undecane via intramolecular asymmetric oxyselenenylation: a new route to optically active spiroketals",,10.1016/s0040-4039(01)00024-7,2001-03-01,0.6299308554897985
Synlett,Synthesis of the C19-C26 Segment of Amphidinolide H2,The synthesis of the C19-C26 methyl ketone of amphidinolide H2 is described employing a stereoselective catalytic vinylogous Mukaiyama aldol reaction. Selective dihydroxylation and deoxygenation completes the synthesis of the C19-C26 segment.,10.1055/s-2005-872236,2005-01-01,0.6299208573709637
Journal of Organic Chemistry,"An Efficient Synthesis of Enantiomerically Pure (<i>R</i>)-Pipecolic Acid, (<i>S</i>)-Proline, and Their<i>N</i>-Alkylated Derivatives",Enantiomerically pure (R)-(+)-pipecolic acid was synthesized in four steps and 42% overall yield starting from dihydropyran and (R)-alpha-methylbenzylamine. A general short strategy is also described for preparing (S)-proline (47.5% overall yield) and derivatives.,10.1021/jo062382i,2007-01-26,0.6299143231951044
European Journal of Organic Chemistry,"Short Synthesis of Idraparinux by Applying a 2‐<i>O</i>‐Methyl‐4,6‐<i>O</i>‐arylmethylene Thioidoside as a 1,2‐<i>trans</i>‐α‐Selective Glycosyl Donor","The fully O ‐sulfated, O ‐methylated, heparin‐related anticoagulant pentasaccharide idraparinux was prepared by a new synthetic pathway in 38 steps using d ‐glucose and methyl α‐ d ‐glucopyranoside as starting materials, with 23 steps for the longest linear route. The l ‐idose‐containing GH fragment was obtained by a short and straightforward synthesis whereby a 4,6‐cyclic‐acetal‐protected l ‐idosyl thioglycoside bearing a C2‐nonparticipating group was used as the α‐selective glycosyl donor. The novel l ‐idose donor was prepared with high chemo‐ and stereoselectivity by hydroboration–oxidation‐based C5 epimerization starting from an orthogonally protected α‐thioglucoside. The assembly of the pentasaccharide backbone was achieved by an F + GH and DE + FGH coupling sequence with full stereoselectivity in each glycosylation step.",10.1002/ejoc.201801349,2018-10-19,0.6299115656730416
Synthesis,"A Simple Method for the Synthesis of 3-Arylthieno[2,3-b]pyridines via Iodine-Mediated Cyclization of 3-(1-Arylalkenyl)-2-[(1-phenylethyl)sulfanyl]pyridines","3-Arylthieno[2,3-b]pyridines are synthesized in a short four-step sequence from readily available 2-bromopyridines. The final and key step of the reported method involves an iodine-mediated 5-endo cyclization of 3-(1-arylalkenyl)-2-[(1-phenylethyl)sulfanyl]pyridines.",10.1055/s-0029-1216857,2009-06-02,0.6298923869986532
Tetrahedron,"Shanzhisin methyl ester gentiobioside, a new iridoid - isolation and synthesis",,10.1016/s0040-4039(00)78742-9,1980-01-01,0.629883415857186
Journal of Organic Chemistry,Total Synthesis of the Antitumor Antibiotic Basidalin,"The first synthesis of the tetronamide antibiotic basidalin was accomplished in five steps and 39% overall yield from readily available 4-bromo-2-triisopropylsilyloxyfuran and 2-formyl-1,3-dithiane. Highlights include: (i) regio- and stereocontrolled assemblage of a pivotal (Z)-γ-ylidene-β-bromobutenolide intermediate by stereodirected vinylogous aldol condensation (SVAC), (ii) installation of the amino group via aza-Michael addition/elimination, and crucially (iii) facile access to basidalin by late-stage dithiane removal.",10.1021/acs.joc.6b01255,2016-06-27,0.6298737272433539
Organic Letters,Diastereoselective Synthesis of <i>ψ</i>[(<i>E</i>)-CMeCH]- and <i>ψ</i>[(<i>E</i>)-CMeCMe]- Type Dipeptide Isosteres Based on Organocopper-Mediated <i>a</i><i>nti</i>-S<sub>N</sub>2‘ Reaction,[reaction: see text] A straightforward synthetic route for the synthesis of diastereomerically pure psi[(E)-CMe=CH]- and psi[(E)-CMe=CMe]-type dipeptide isosteres was developed on the basis of regio- and stereoselective anti-S(N)2' alkylation of 3-(N-Boc-5-methyl-4-substituted-oxazolidin-2-on-5-yl)acrylates with organocopper reagents.,10.1021/ol016835b,2002-03-05,0.6298720407245846
Tetrahedron,"A new synthesis of 1,4-diketones: application to the synthesis of -jasmone",,10.1016/s0040-4039(01)96923-0,1971-01-01,0.6298699455128328
Synthesis,Synthesis of Polyprenylacetones and -acetates; Application to a New Synthesis of Gefarnate,,10.1055/s-1981-29599,1981-01-01,0.6298699455128328
Journal of the American Chemical Society,Sequential Catalytic Asymmetric Heck−Iminium Ion Cyclization:  Enantioselective Total Synthesis of the <i>Strychnos </i>Alkaloid Minfiensine,"A catalytic asymmetric method for the chemical synthesis of alkaloids containing the 1,2,3,4-tetrahydro-9a,4a-(iminoethano)-9H-carbazole (1) moiety is reported and verified by the enantioselective total synthesis of (+)-minfiensine (4). The central step in this total synthesis is the sequential catalytic asymmetric Heck-N-acyliminium ion cyclization of dienyl carbamate triflate 10, prepared in six steps from 1,2-cyclohexanedione, to give enantiopure 3,4-dihydro-9a,4a-(iminoethano)-9H-carbazole (12) in 75% yield. Iminoethano-9H-carbazole 12 is transformed in six steps to dienyl iodide 17, which undergoes diastereoselective intramolecular Heck cyclization to form pentacyclic intermediate 18. In eight additional steps, this latter intermediate is transformed to (+)-minfiensine (4).",10.1021/ja0533895,2005-07-01,0.6298629996520752
Tetrahedron,Studies directed toward the total synthesis of kabiramide C: Asymmetric synthesis of the C7–C19 fragment,The synthesis of the C7C19 tris-oxazole fragment 4 of kabiramide C via a BF3·OEt2 promoted condensation between dimethyl acetal 12 and (S)-silane 6 as the crucial synthetic step is described.,10.1016/s0040-4039(98)01298-2,1998-08-01,0.6298543317757763
Synthesis,Synthesis of (±)-3-Amino-2-(4-chlorophenyl)propanesulfonic acid (Saclofen),"All articles of this category An efficient synthesis of saclofen, a putative GABA B antagonist, is reported.",10.1055/s-1991-26437,1991-01-01,0.6298349749816526
Organic Process Research & Development,Development of a Chemoenzymatic Route to (<i>R</i>)-Allyl-(3-amino-2-(2-methylbenzyl)propyl)carbamate,"A chemoenzymatic route to ( R )-allyl-(3-amino-2-(2-methylbenzyl)propyl)carbamate ( 1 -( R )) has been developed on a kilogram scale. The key intermediate, 2-(2-methylbenzyl)propane-1,3-diamine 4, was isolated as a tartrate salt in a three-step sequence starting from 2-methylbenzyl chloride. The subsequent lipase-catalyzed desymmetrization was optimized, and 1 -( R ) was isolated as the d -tartrate salt.",10.1021/acs.oprd.5b00326,2015-12-17,0.6298023143280106
Tetrahedron,Palladium-catalyzed regioselective oxidative amination of alkenes: an efficient route to the synthesis of pyrrolocoumarin and pyrroloquinolone derivatives,,10.1016/j.tetlet.2010.05.068,2010-06-11,0.6297908147069714
Organic Process Research & Development,Development of an Efficient Synthesis of Two CRF Antagonists for the Treatment of Neurological Disorders,"BMS-764459 ( 1 ) and BMS-763534 ( 2 ) are CRF1 antagonists for the treatment of neurological disorders such as depression and anxiety. An efficient synthesis of 1 and 2 is described, which features an efficient palladium-catalyzed cyanation of a 5-chloropyrazinone where zinc acetate suppresses dehalogenation. This synthesis was applied to the preparation of >5 kg of 1 and 2 for clinical studies.",10.1021/op1001512,2010-07-29,0.62978546889691
Tetrahedron,Synthesis of sesquiterpene antitumor lactones I a facile synthesis of -fused-a-ring in vernolepin and vernomenin,,10.1016/s0040-4039(01)92731-5,1977-01-01,0.6297758034804607
Journal of Organic Chemistry,Synthesis of a Library of Propargylated and PEGylated α-Hydroxy Acids Toward “Clickable” Polylactides via Hydrolysis of Cyanohydrin Derivatives,"A new simple and practical protocol for scalable synthesis of a novel library of propargylated and PEGylated α-hydroxy acids toward the preparation of ""clickable"" polylactides was described. The overall synthesis starting from readily available propargyl alcohol, bromoacetaldehyde diethyl acetal, and OEGs or PEGs was developed as a convenient procedure with low cost and no need of column chromatographic purification. The terminal alkyne functionality survives from hydrolysis of the corresponding easily accessible cyanohydrin derivatives in methanolic sulfuric acid. Facile desymmetrization, monofunctionalization, and efficient chain-elongation coupling of OEGs further enable the incorporation of OEGs to α-hydroxy acids in a simple and efficient manner. At the end, synthesis of allyloxy lactic acid indicates that an alkene group is also compatible with the developed method.",10.1021/jo5016135,2014-09-25,0.6297705693486064
Synlett,Cyclization of Bicyclic Diterpenes Promoted by SmI2. Synthesis of Tri- and Tetracyclic Diterpenes,The synthesis of 15-hibaen-14-one (a tetracyclic diterpene) is described from zamoranic acid as starting material in an excellent yield and with total control of the stereochemistry. The key step is a SmI2 promoted pinacol cyclization.,10.1055/s-2002-20465,2002-01-01,0.6297693817029768
Tetrahedron,Synthesis of indole alkaloid (−)-corynantheidol and formal synthesis of (−)-corynantheidine via one-pot asymmetric azaelectrocyclization,,10.1016/j.tetlet.2009.05.045,2009-05-23,0.6297664064295078
Organic Process Research & Development,"A New Process for Synthesis of the Astrocyte Activation Suppressor, ONO-2506","Development of a new process for the synthesis of ONO-2506, an agent that suppresses astrocyte activation, is described. Previous processes that involved asymmetric synthesis with a chiral auxiliary were unsatisfactory from a cost perspective because the relatively expensive chiral auxiliaries were not recyclable. To develop a more cost-effective process, we designed a new process starting from chiral 1,2-epoxyoctane, which was readily prepared catalytically by Prof. Jacobsen's method. The new five-step process was developed with the establishment of a modified cyanation condition, in which lithium cyanide was prepared in situ by combining lithium hydroxide with acetone cyanohydrin. Then the mechanisms for racemization and the side reaction until the cyanation step were clarified, and these problems were solved. The main features of this process are crystallization of the amide intermediate, since its optical purity is readily improved by recrystallization up to 100% ee in addition to formation of the dibenzylamine salt with ONO-2506 that leads to improved chemical and optical purity of the final product. The shorter synthesis, including a one-pot reaction was ruled out because of the hazardous nature of the Katriztky hydrolysis conditions for the conversion of nitrile to amide in the presence of sodium cyanide.",10.1021/op0500988,2005-09-07,0.629763062509209
Angewandte Chemie International Edition,Concise Total Synthesis of (−)-Frondosin B Using a Novel Palladium-Catalyzed Cyclization,"Sidestepping stereochemical inversion: In an expedient, asymmetric total synthesis of (−)-frondosin B a novel palladium-catalyzed cyclization establishes the tetracyclic skeleton (see scheme). The absolute stereochemistry of naturally occurring marine metabolite (+)-frondosin B, an interleukin-8 inhibitor, has been reassigned. Tf=trifluoromethanesulfonyl.",10.1002/1521-3773(20020503)41:9<1569::aid-anie1569>3.0.co;2-8,2002-05-02,0.6297492460744457
Tetrahedron,A short efficient synthesis of -dibenzylbutyrolactones exemplified by the synthesis of di-o-methyl compound x (HPMF) and an anti-tumour extractive.,,10.1016/s0040-4039(01)90374-0,1981-01-01,0.6297486818112079
Organic Letters,A New Synthesis of Lysergic Acid,[reaction: see text] (+/-)-Lysergic acid has been synthesized via an economical 8-step route from 4-bromoindole and isocinchomeronic acid without the need to protect the indole during the synthesis. Initial efforts to form the simpler 3-acylindole derivatives first and then cyclize these were unsuccessful in the cyclization step.,10.1021/ol0354369,2003-12-10,0.6297470518612562
Organic Letters,New Entry to Convertible Isocyanides for the Ugi Reaction and Its Application to the Stereocontrolled Formal Total Synthesis of the Proteasome Inhibitor Omuralide,"The development of a new convertible isocyanide, indole-isocyanide, for ready access to pyroglutamic acids culminated in the formal total synthesis of the proteasome inhibitor omuralide featuring a stereocontrolled Ugi reaction. Indole-isocyanide was named after the facilitation of hydrolysis of the resulting 2-(2,2-dimethoxyethyl)anilide via an N-acylindole intermediate obtained by the Ugi multicomponent condensation reaction followed by the indole formation.",10.1021/ol701446y,2007-08-01,0.6297340992778432
Tetrahedron,Diastereoselective synthesis of 2-aryl-3-aminoazepanes via a novel ring-enlargement process,,10.1016/s0040-4039(99)02256-x,2000-02-01,0.6297316494847706
Organic Process Research & Development,"Process Development, Impurity Control, and Production of a Novel Tubulin Inhibitor","Process development and production of a novel tubulin inhibitor are described. The desired API was obtained through selective iodination of the 12′ position of vinblastine and subsequent thiomethylation. Most of the impurities were identified, and process parameters were adjusted to control such impurities. The optimized process was scaled up under cGMP conditions to afford 230 g of the desired API.",10.1021/op3002307,2012-09-28,0.6297283854070088
Journal of Organic Chemistry,A Modular Enantioselective Approach to Construction of the Macrolactone Core of Polycavernoside A,"A program directed toward a total synthesis of polycavernoside A is described. The synthesis of five building blocks is detailed. The first of two electrophilic units, the lactone 3, was prepared in four steps from the known enantiomerically pure oxirane 15. Pyranyl aldehyde 5 was elaborated in turn from L-malic acid via 10. While the route to 30 involved 3 as a starting material, dithiane 2 was obtained in a straightforward manner from 10 as well. The merging of the chiral sectors could not be accomplished by way of the lithiated dithianyl anions, presumably as a consequence of their heightened basicity. The strategic incorporation of the trienyl sector was accomplished, although no attempt was made to control the diastereoselectivity of the process.",10.1021/jo981083t,1998-10-01,0.6297257229128879
Synlett,Cope-House Cyclization Strategy for the Synthesis of Pyrrolizidines: An Expedient Route to 5-<i>epi</i>-Hyacinthacine A<sub>3</sub> and 5-<i>epi</i>-Hyacinthacine A<sub>5</sub>,An expedient Cope-House cyclization strategy is reported here for the synthesis of several polyhydroxy pyrrolizidine alkaloids starting from sugar-derived nitrones.,10.1055/s-2008-1042898,2008-03-20,0.6297093252862491
Organic Letters,Total Synthesis of Meayamycin and <i>O</i>-Acyl Analogues,"A short, scalable total synthesis of meayamycin is described by an approach that entails a longest linear sequence of 12 steps (22 steps overall) from commercially available chiral pool materials (ethyl l -lactate, BocNH-Thr-OH, and d -ribose) and introduces the most straightforward preparation of the right-hand subunit detailed to date. The use of the approach in the divergent synthesis of a representative series of O -acyl analogues is exemplified.",10.1021/acs.orglett.0c03308,2020-10-19,0.6297053912528363
Journal of Organic Chemistry,Total Synthesis of (−)-Muscoride A,"The recently isolated cyanobacterium metabolite muscoride A was synthesized in 15 steps and in 4.3% overall yield. Novel structural features of this peptide antibiotic include the presence of a threonine-derived bioxazole core and an N-(1,1-dimethyl)allyl (""reverse prenyl"") valine residue. In the context of our synthesis, efficient new strategies for the preparation of these segments were developed. The synthesis of two epimers of muscoride A allowed the unambiguous assignment of the relative and absolute configuration of the natural product by NMR and optical rotation analyses.",10.1021/jo960891m,1996-01-01,0.6297022759953605
Organic Process Research & Development,"A New Practical Route for the Manufacture of (4aR,10aR)-9-Methoxy-1-methyl-6-trimethylsilanyl- 1,2,3,4,4a,5,10,10a-octahydrobenzo[<i>g</i>]quinoline","Different synthetic routes to the enantiomerically pure octahydrobenzo[ g ]quinoline derivative JNZ092 were evaluated for their suitability to rapidly prepare a first clinical batch on a kilogram scale. On the basis of the experience of previous octahydrobenzo[ g ]quinoline projects a new linear synthesis of JNZ092 was established and scaled up successfully. The overall yield was increased by a factor 10 and the preparation time shortened significantly as compared to those of the medicinal chemistry route. As the key strategy all atoms of the octahydrobenzo[ g ]quinoline skeleton were introduced early by the reaction of the 6-lithiated 1,7-dimethoxynaphthalene with ethyl-2-cyano-3-ethoxyacrylate. As a valuable technological refinement the practicability of a chromatographic technique with repetitive feed injection for the problematic separation of the enantiomers was demonstrated.",10.1021/op034112x,2003-11-01,0.6296922019615647
Journal of Organic Chemistry,Asymmetric Total Synthesis of Lancifodilactone G Acetate. 1. Diastereoselective Synthesis of CDEFGH Ring System,"The stereoselective construction of the CDEFGH ring system of lancifodilactone G is described. The key steps in this synthesis are (i) ring-closing metathesis for formation of the oxa-bridged eight-membered ring; (ii) an intramolecular Pauson-Khand reaction for construction of the sterically congested F ring; and (iii) sequential cross-metathesis, hydrogenation, and lactonization reactions for installation of the anomerically stabilized bis-spiro ketal fragment of lancifodilactone G.",10.1021/acs.joc.7b02915,2018-03-06,0.6296903146589996
Synthesis,Total Synthesis of (+)-Dodoneine and Its 6-Epimer,"The total synthesis of dodoneine and its 6-epimer is described­, using HKR of epoxide and reduction with SmI2 reactions as key steps, respectively.",10.1055/s-0029-1216953,2009-08-21,0.629659069615064
Organic Letters,"Liphagal, a Selective Inhibitor of PI3 Kinase α Isolated from the Sponge <i>Aka </i><i>c</i><i>oralliphaga</i>:  Structure Elucidation and Biomimetic Synthesis","[structure: see text] Liphagal (1), a selective inhibitor of PI3K alpha, has been isolated from the marine sponge Aka coralliphaga collected in Dominica. The ""liphagane"" meroterpenoid carbon skeleton of liphagal (1) is new. A biomimetic total synthesis has been used to confirm the constitution of liphagal (1) and support a proposed biogenesis.",10.1021/ol052744t,2005-12-18,0.6296368660451643
Synthesis,"A Novel One Step Synthesis of 5(3)-Methylthio-, Alkoxy-, Amino- and Hydroxypyrazoles using α-Ketoketene-<i>S</i>,<i>S</i>-Diacetals",,10.1055/s-1975-23935,1975-01-01,0.6296349077689908
Synthesis,Scalable and Cost-Effective Synthesis of a Linker for Bioconjugation with a Peptide and a Monoclonal Antibody,"An efficient, scalable, and cost-effective synthesis of a linker employed in a bioconjugation process with a peptide and a monoclonal antibody is presented. Several routes were investigated that resulted in the identification of a short synthesis to a key acid intermediate from inexpensive and readily available starting materials. The final coupling of this acid with an aniline to afford the desired linker has been optimized to produce multi-gram quantities of material for clinical studies. The very limited purifications needed for both intermediates and final product make this route amenable to scale.",10.1055/s-0033-1340980,2014-03-17,0.6296345213203933
European Journal of Organic Chemistry,"Stereoselective Synthesis of (2<i>S</i>,4<i>R</i>)‐4‐Hydroxypipecolic Acid","Abstract A new synthetic route to enantiopure (2 S ,4 R )‐4‐hydroxypipecolic acid from commercial ethyl (3 S )‐4‐chloro‐3‐hydroxybutanoate is reported. The synthesis is based on the Pd‐catalyzed methoxycarbonylation of a 4‐alkoxy‐substituted δ‐valerolactam‐derived vinyl triflate followed by the stereocontrolled hydrogenation of the enamine double bond. The final product was obtained after exhaustive hydrolysis in 20 % yield over 10 steps. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2008)",10.1002/ejoc.200700849,2007-11-20,0.6296334226644265
Organic Process Research & Development,"Development of a Scaleable Process for the Synthesis of the A2a Agonist, UK-371,104","The development and utilization of a scaleable process for the manufacture of the A2a agonist UK-371,104 ( 1 ) is described. Key steps in the synthesis include (i) a palladium-catalyzed cyanation reaction to prepare the nitrile 10, (ii) a telescoped conversion of the acid 11 to the glycosidation substrate 9, and (iii) the stereoselective coupling of 8 with 9 in a glycosidation reaction mediated by TMS triflate in 1,2-dimethoxyethane followed by conversion through to 1 .",10.1021/op700248t,2008-05-21,0.6296297197828082
Journal of Organic Chemistry,Two Approaches toward the Formal Total Synthesis of Oseltamivir Phosphate (Tamiflu): Catalytic Enantioselective Three-Component Reaction Strategy and <scp>l</scp>-Glutamic Acid Strategy,"Two independent formal total syntheses of oseltamivir phosphate were successfully achieved: the first utilized a copper-catalyzed asymmetric three-component reaction strategy, and the second utilized L-glutamic acid γ-ester as a chiral source to install the correct stereochemistry. Both strategies used Dieckmann condensation to construct a six-membered ring core, after which manipulation of the functional groups and protecting groups accessed Corey's intermediate for the synthesis of oseltamivir phosphate. While the first synthesis was accomplished via four purification steps in 25.7% overall yield, albeit with moderate optical purity (76% ee), the second strategy achieved the synthesis via six purification steps in 19.8% overall yield with perfect enantiocontrol.",10.1021/jo400360j,2013-03-21,0.6296266856953274
Angewandte Chemie International Edition,Bioinspired Total Synthesis of (−)‐Vescalin: A Nonahydroxytriphenoylated <i>C</i>‐Glucosidic Ellagitannin,"The first total synthesis of the 2,3,5-O-(S,R)-nonahydroxytriphenoylated (NHTP) C-glucosidic ellagitannin (-)-vescalin was accomplished through a series of transformations mimicking the sequence of events leading to its biogenesis. The key steps of this synthesis encompass a Wittig-mediated ring opening of a glucopyranosic hemiacetal, a C-glucosidation event through a phenolic aldol-type reaction, and a Wynberg-Feringa-Yamada-type oxidative phenolic coupling, which forged the NHTP unit of (-)-vescalin.",10.1002/anie.201707613,2017-08-31,0.6296140511539172
Journal of Organic Chemistry,Synthesis of Terpenoids Using a Free Radical Fragmentation/Elimination Sequence,"Total syntheses of the guaiane alismol 8 and the trinor-guaiane dictamnol 18 are reported. In both syntheses the initial [2+2] photoadduct is transformed into an iodo xanthate 14 or a diiodide 27, respectively. In the critical step, the strained bifunctional substrate undergoes a very efficient free radical fragmentation/elimination sequence to give the requisite seven-membered ring with regioselective placement of the two double bonds in that ring. This first alismol synthesis was accomplished in eight steps while the dictamnol synthesis required only six steps. Clarification of the structure of dictamnol is also described.",10.1021/jo990307k,1999-08-19,0.6296011211034767
Synthesis,Sphingosines - an Oxa-Cope Rearrangement Route for Their Synthesis,"All articles of this category Various methods for the synthesis of sphingosine (1) and phytosphingosine (2) have been reported. Some are based on starting materials derived from the chiral pool. In this paper, it is demonstrated that the generally required trans -selective C=C bond formation, with concomitant chain extension and the introduction of the amino group, can be achieved starting from 2,4-di- O -protected D-threose 6 , itself readily available from D-galactose. For instance, the sequence vinylmagnesium bromide addition to 6 (→ 7a, x) , regioselective 3- O -mesylation (→ 8a, x) , oxa-Cope rearrangement by treatment with trimethyl orthoacetate (→ 9) , azido group introduction (→ 14) , deprotection, and azido group reduction, yields the novel sphingosine 17 . Oxa-Cope rearrangements with other ortho esters and with 3- O -benzoyl-protected vinylcarbinol precursors 22a, x were also investigated, for instance, for the synthesis of truncated sphingosines. sphingosine - phytosphinganine - synthesis - oxa-Cope rearrangement - chiral pool",10.1055/s-1995-3998,1995-07-01,0.6295943505867946
Journal of Organic Chemistry,Total Syntheses of (±)-Anchinopeptolide D and (±)-Cycloanchinopeptolide D,"The first synthesis of (+/-)-anchinopeptolide D (4) has been accomplished in seven steps in 10% overall yield from octopamine hydrochloride (17), N-(Boc)glycine (16), and 5-amino-2-hydroxypentanoic acid (22). The key step is the aldol dimerization and hemiaminal formation of alpha-keto amide 26, which gives primarily protected anchinopeptolide D 27 under kinetically controlled conditions. Cycloanchinopeptolide D (31) has been prepared by the unprecedented head-to-head photodimerization of the two hydroxystyrylamides of 4 using the hydrophobic effect in water to force the two side chains into close proximity so that [2 + 2] cycloaddition is faster than trans to cis double bond isomerization. Coupling of amine 21 with pyroglutamic acid affords the naturally occurring tripeptide 35, which had been assigned glutamic acid structure 34.",10.1021/jo991454l,2000-01-14,0.6295903184781165
Organic Letters,Total Syntheses of Galanthamine and Lycoramine via a Palladium-Catalyzed Cascade Cyclization and Late-Stage Reorganization of the Cyclized Skeleton,"Herein, we report the highly efficient total syntheses of galanthamine and lycoramine from a common tetracyclic intermediate. This concise synthetic route features a two-phase strategy, which includes the early-stage rapid construction of a tetracyclic skeleton followed by the late-stage selective reorganization of the tetracyclic skeleton. Key to the success of this strategy are a palladium-catalyzed carbonylative cascade annulation, a DDQ-mediated intramolecular regioselective oxidative lactamization, as well as a BF 3 ·Et 2 O-promoted reorganization of the bridged tetracyclic skeleton.",10.1021/acs.orglett.1c03943,2021-12-07,0.6295866433774768
European Journal of Organic Chemistry,Convergent Synthesis and Biological Evaluation of Syringolin A and Derivatives as Eukaryotic 20S Proteasome Inhibitors,"Abstract A convergent synthesis of SylA was developed and consists of the synthesis of a fully functionalized macrocycle, which is subsequently coupled with a urea moiety. For cyclization, ring‐closing metathesis of a conformationally preorganized precursor was employed. The established synthetic route was then applied to the synthesis of SylA derivatives by using various peptidic side chains for decoration of the SylA macrocycle. The resulting collection of SylA analogues was tested for proteasome inhibition, revealing PEGylated SylA derivatives as the most potent proteasome inhibitors.",10.1002/ejoc.201000317,2010-05-20,0.6295643657480278
European Journal of Organic Chemistry,"Total Synthesis of TAN-1057 A/B, a New Dipeptide Antibiotic fromFlexibacter sp. PK-74","TAN-1057 (1a, b) − a new natural dipeptide antibiotic active against methicillin resistant strains of Staphylococcus aureus − was synthesized starting from Nα, Nδ, Nω-tri-Z-L-arginine 20b via the corresponding diazoketone 21b. This upon photolysis rearranged to the ketene which was trapped by (±)-2,4,5,6-tetrahydro-5-methylamino-2-ureidopyrimidin-4-one (3) to yield the fully protected dipeptide 23 (30%). The latter was deprotected by hydrogenolysis to give the final compound as a mixture of two epimers − TAN-1057A, B − isolated previously from a strain of Flexibacter sp. PK-74. The intermediate 3 was prepared from 3-amino-2-(N-Z-N-methylamino)propionic acid methyl ester hydrochloride (16) and 2-methyl-2-thiopseudobiuret hydroiodide (18) in one step in 35% yield.",10.1002/(sici)1099-0690(199805)1998:5<777::aid-ejoc777>3.0.co;2-w,1998-05-01,0.6295578083243426
Synthesis,A Simple and Efficient Asymmetric Synthesis of Anxiolytic Drug Enciprazine,"A straightforward and efficient asymmetric synthesis of (S)-1-[4-(2-methoxyphenyl)piperazin-1-yl]-3-(3,4,5-trimethoxyphen­oxy)propan-2-ol is described. The key intermediate, (S)-2-[(3,4,5-trimethoxyphenoxy)methyl]oxirane, was obtained by a hydrolytic kinetic resolution method using the catalyst (R,R)-salen-cobalt(III) complex.",10.1055/s-0030-1258173,2010-07-12,0.6295574981604941
Synthesis,Efficacious Preparation of Oppolzer’s Glycylsultam via the Delépine Reaction,"A new preparative route to Oppolzer’s glycylsultam, the ‘NC’ component in the asymmetric [C+NC+CC] coupling reaction leading to functionalized pyrrolidines, is described. The synthesis features a novel application of the Delépine reaction, providing a safe, efficient, and environmentally benign route to this useful chiral reagent for pyrrolidine synthesis.",10.1055/s-0028-1088021,2009-03-16,0.629546214234721
Journal of Organic Chemistry,Total Synthesis of Penicyclone A Using a Double Grignard Reaction,"We describe the first total synthesis of penicyclone A, a novel deep-sea fungus-derived polyketide, and a reevaluation of its antimicrobial activity. The synthesis of this unique spirolactone was achieved in 10 steps starting from a known d-ribose derivative. The key steps include a double Grignard reaction for the diastereoselective construction of the chiral tertiary alcohol intermediate, tandem oxidation/cyclization, and photooxygenation, followed by an oxidative rearrangement to introduce the enone functionality.",10.1021/acs.joc.2c02200,2022-11-16,0.629533606712522
Organic Letters,A Divergent Approach to the Diastereoselective Synthesis of Several Ant-Associated Iridoids,"The ant-associated iridoids nepetalactol, actinidine, dolichodial, isoiridomyrmecin, and dihydronepetalactone were prepared from citronellal using a divergent approach. Key features include a three-step synthesis of the individual antipodes of actinidine by a novel tandem cycloaddition/pyridine formation and a facile diastereoselective synthesis of both enantiomers of dolichodial.",10.1021/ol100077z,2010-03-11,0.629505366532682
Synthesis,"A Novel Synthesis of Tetrahydropyrazolo[1,5-c]pyrimidine-2,7(1H,3H)-diones","A novel simple five-step synthesis of 1,6-disubstituted tetrahydropyrazolo[1,5- c ]pyrimidine-2,7(1 H ,3 H )-diones has been developed. The synthetic protocol starts with ‘ring switching’ transformation of commercially available 5,6-dihydro-2 H -pyran-2-one into the 5-(2-hydroxyethyl)pyrazolidin-3-one, followed by addition of the latter to isocyanates, Appel bromination, cyclization, and N(1)-alkylation with alkyl halides to give the title compounds. In comparison to a 12-step synthesis reported recently, the present method is clearly superior with respect to the number of synthetic steps and versatility of substituents at position 6.",10.1055/s-0033-1339977,2013-10-18,0.6295042783288172
Organic Process Research & Development,Synthesis of (<i>S</i>)-3-(<i>N</i>-Methylamino)-1-(2-thienyl)propan-1-ol:  Revisiting Eli Lilly's Resolution−Racemization−Recycle Synthesis of Duloxetine for Its Robust Processes,"(±)-3-( N, N -Dimethylamino)-1-(2-thienyl)propan-1-ol ( 6 ), prepared from 2-acetylthiophene ( 4 ) in a two-step overall yield of 79%, is resolved into ( S )- 6 of 93% ee as its diastereomeric salt ( 8 ) with ( S )-mandelic acid ( 7 ) according to Eli Lilly's procedures developed for the resolution−racemization−recycle (RRR) synthesis of duloxetine ( 2 ) with some modifications in terms of practicality. On its liberation from 8, ( S )- 6 undergoes N -demethylative ethyl carbamate formation in two discrete but successive steps in an overall yield of 87% from 8: (1) O -ethyl carbonate formation and (2) ethyl carbamate formation with concomitant loss of the N -methyl group. Alkaline hydrolysis then affords ( S )-3-( N -methylamino)-1-(2-thienyl)propan-1-ol ( 1 ) of 100% ee, an alleged penultimate precursor to duloxetine ( 2 ), in 75% yield after a single recrystallization from ethylcyclohexane. In the overall process thus developed, PhMe is substituted successfully for t -BuOMe, a solvent that has been used favorably in Eli Lilly's original RRR synthesis of 2 .",10.1021/op060118l,2006-09-01,0.6295006406344404
Organic Letters,An Efficient Synthesis of (±)-Trichostatic Acid and Analogues: A New Route to (±)-Trichostatin A,"An efficient synthesis of rac-trichostatic acid (1) and its analogues is reported starting from a commercially available aldehyde. Further manipulations of rac-1 led to rac-trichostatin A (TSA). Construction of the desired molecular architecture entails a two-component union, achieved through an in situ hydroboration followed by a Suzuki-Miyaura coupling with 2. The requisite homopropargyl alcohol was synthesized by exploiting allenylindium chemistry. This new protocol paved the way for the synthesis of analogues of trichostatic acid and hence TSA.",10.1021/ol9029116,2010-01-27,0.6294902543231233
Tetrahedron,Cyclization reactions of 4-(3′-butenyl)azetidin-2-one a route to the carbopenam ring system,,10.1016/s0040-4039(01)86770-8,1979-01-01,0.629474164885125
Tetrahedron,Improved enantioselective synthesis of natural striatenic acid and its methyl ester,,10.1016/j.tetlet.2006.03.147,2006-04-13,0.6294706502828757
Angewandte Chemie International Edition,Total Synthesis of Dermostatin A,"An oxo-hexaene macrolide antibiotic, dermostatin A has been synthesized. Key features of the synthesis include the application of cyanohydrin acetonide couplings for the synthesis of the polyol portion, and the convergent introduction of the polyene segment by means of a Stille coupling.",10.1002/1521-3773(20010903)40:17<3224::aid-anie3224>3.0.co;2-d,2001-09-03,0.6294577619826822
Organic Process Research & Development,Palladium-Catalyzed C–O Coupling of a Sterically Hindered Secondary Alcohol with an Aryl Bromide and Significant Purity Upgrade in the API Step,"The final two steps used to prepare greater than 1 kg of a compound evaluated as a treatment for type 2 diabetes are reported. The application of a palladium-catalyzed C–O coupling presented significant challenges due to the nature of the reactants, impurities produced, and noncrystalline coupling intermediate. Process development was able to address these limitations and enable production of kilogram quantities of the active pharmaceutical ingredient (API) in greater efficiency than a Mitsunobu reaction for formation of the key bond. The development of a sequence that telescopes the coupling with the subsequent ester hydrolysis to yield the API and the workup and final product crystallization necessary to produce high-quality drug substance without the need of column chromatography are discussed.",10.1021/acs.oprd.8b00022,2018-03-29,0.6294397644096611
Journal of Organic Chemistry,Total Synthesis of the Ethyl Ester of the Major Urinary Metabolite of Prostaglandin E<sub>2</sub>,The preparation of the ethyl ester of the major urinary metabolite of prostaglandin E(2) 3 is described. The key step is the kinetic opening of the TBS-protected bicyclic ketone 7 with thiophenol.,10.1021/jo011017i,2002-02-01,0.6294370736525525
Journal of the American Chemical Society,Asymmetric Total Synthesis of (−)-Quinocarcin,"(-)-Quinocarcin (1) has been synthesized in a longest linear sequence of 22 steps from 3-hydroxybenzaldehyde in 16% overall yield. The Pictet-Spengler reaction of L-tert-butyl-2-bromo-5-hydroxy phenylalanate (17), synthesized according to Corey-Lygo's enantioselective alkylation process, with benzoxyacetaldehyde (12) under mild acidic conditions afforded 1,3-cis tetrahydroisoquinoline 20 as an only isolable stereomer in 91% yield. The diazabicycle[3,2,1]-octane ring system of 28 was constructed by a silver tetrafluoroborate-promoted intramolecular Mannich reaction using amino thioether as a latent N-acyliminium species and tethered silyl enol ether as a nucleophile. Using amino thioether instead of aminal as a precursor of N-acyliminium was of high importance to the success of this otherwise disfavored 5-endo-Trig cyclization. A Hf(OTf)4-catalyzed (0.1 equiv) transformation of aminal to amino thioether was uncovered in the course of this study, allowing the conversion of tricyclic aminal 24 to amino thioether 25 to be realized in high yield. From the bridged tetracyclic compound 28, a sequence of oxidation of aldehyde to acid, global deprotection under hydrogenolysis conditions, and one-pot partial reduction of lactam to aminal/oxazolidine formation completed the total synthesis of the pentacyclic (-)-quinocarcine.",10.1021/ja800662q,2008-05-03,0.6294355458521604
Synthesis,"Selective Sulphonylation with<i>N</i>-Tosylimidazole. A One-Step Preparation of Methyl 2,3-Anhydro-4,6-<i>O</i>-benzylidene-α-D-mannopyranoside",,10.1055/s-1974-23284,1974-01-01,0.629434156991434
Angewandte Chemie International Edition,Total Synthesis of Piperazimycin A: A Cytotoxic Cyclic Hexadepsipeptide,"Pied piper: The first total synthesis of the title compound 1, a potent cytotoxic natural product has been achieved. The key elements include an efficient synthesis of the difficult-to-install (R,S)-γClPip/(S,S)-γOHPip dipeptide fragment as well as macrocyclization by an SN2 reaction of an N-2-chloroacetyl moiety with a carboxylate anion.",10.1002/anie.200904603,2009-10-16,0.6294207835818199
Angewandte Chemie International Edition,Enantiospecific Total Synthesis of <i>N</i>‐Methylwelwitindolinone D Isonitrile,The total synthesis of N-methylwelwitindolinone D isonitrile (1) has been achieved in 17 steps from a readily available carvone derivative. The route features a double C-H functionalization event involving a keto oxindole substrate to introduce the tetrahydrofuran ring of the natural product.,10.1002/anie.201307464,2013-10-02,0.6294202905604053
Synthesis,Cyclotryptophan Mycotoxins: Short Synthesis of the Desymmetrized meso-Chimonantine Core of Leptosin C,The desymmetrized meso -chimonantine core of leptosin C was prepared in a short stereoselective convergent sequence in 5 steps as the longest linear path from methyl l -tryptophan hydrochloride as starting material. The key step of this approach was a diastereoselective [4+2] cycloaddition between the bromooxindole and tryptophan derivatives allowing to define the adjacent quaternary benzylic centers in a high chemical yield.,10.1055/s-0036-1588355,2016-12-01,0.6294046182290179
Organic Process Research & Development,Development of an Improved Synthetic Process of Clonazepam by Preventing the Formation of a Trimeric Compound in the Presence of HCl,"An improved synthesis process of clonazepam was developed with the key parameters determined. The trimer intermediate ( 9 ) of clonazepam prepared by using the one-pot method was isolated and identified for the first time. It was further confirmed that the depolymerization of 9 at high temperature was the rate-determining step for the preparation of clonazepam by using the one-pot method, which results in a low yield and purity. 2-Amino- N -(2-(2-chlorobenzoyl)-4-nitrophenyl) acetamide hydrochloride (7·HCl) was a key intermediate separated in the improved process, and the method of its synthesis with high purity to avoid the production of 9 was further reported. The improved process performed better in terms of efficiency and robustness. Besides, the high-performance liquid chromatography purity and total yield of clonazepam obtained by using the improved method were 99.98% and 57%, respectively.",10.1021/acs.oprd.2c00023,2022-04-06,0.6293960243616082
Organic Letters,Ten-Step Total Synthesis of (−)-Andranginine,"The total synthesis of the indole alkaloid (−)-andranginine has been achieved in 10 steps. Key reactions of the synthesis include a nucleophilic addition of acetylenyl anion to chiral N -sulfinyl imine, an intramolecular N -alkylation reaction to close the C ring, and a dienyne metathesis cascade reaction to construct the DE rings. Meanwhile, 16- epi -(−)-andranginine was also obtained with the developed strategy.",10.1021/acs.orglett.2c02927,2022-09-13,0.6293783556625144
Journal of the American Chemical Society,Synthesis of (−)-Isonitrin B,"The first enantioselective synthesis of (−)-isonitrin B ( 2 ), the parent of a small family of isonitrile antibiotics having compact but highly functionalized (and highly reactive) cyclopentane rings, is described. They key in this synthesis is the cyclization of 5b to 4b, by way of the intermediate alkylidene carbene.",10.1021/ja981700v,1998-12-01,0.6293778342147421
Angewandte Chemie International Edition,Stereoselective Mukaiyama-Michael/Michael/Aldol Domino Cyclization as the Key Step in the Synthesis of Pentasubstituted Arenes: An Efficient Access to Highly Active Inhibitors of Cholesteryl Ester Transfer Protein (CETP),"Seemingly heartbreaking for a stereochemist, the one-step selective construction of a stereopentad and its prompt destruction by aromatization has been proven to be an efficient strategy for the synthesis of fivefold substituted, pharmacologically highly active arenes (see scheme).",10.1002/(sici)1521-3773(19991115)38:22<3373::aid-anie3373>3.0.co;2-f,1999-11-15,0.6293722288293848
Organic Letters,Enantioselective Synthesis of Cyclohepta[<i>b</i>]indoles: Gram-Scale Synthesis of (<i>S</i>)-SIRT1-Inhibitor IV,An enantioselective gram-scale synthesis of one of the most potent SIRT1-inhibitors has been accomplished by an unprecedented domino reaction sequence establishing the cyclohepta[b]indole core. This method was developed for application in natural product synthesis of a variety of indole alkaloids.,10.1021/ol4026217,2013-10-23,0.6293697684164384
Journal of Organic Chemistry,"Enantioselective Total Synthesis of (+)-EBC-23, a Potent Anticancer Agent from the Australian Rainforest","We describe here an enantioselective synthesis of (+)-EBC-23, a potent anticancer agent from the Australian rainforest. Our convergent synthesis features a [3+2] dipolar cycloaddition of an olefin-bearing 1,3- syn diol unit and an oxime segment containing 1,2- syn diol functionality as the key step. The segments were synthesized in a highly enantioselective manner using Noyori asymmetric hydrogenation of a β-keto ester and Sharpless asymmetric dihydroxylation of an α,β-unsaturated ester. Cycloaddition provided isoxazoline derivative which upon hydrogenolysis furnished the β-hydroxy ketone expediently. A one-pot, acid-catalyzed reaction removed the isopropylidene group, promoted spirocyclization, constructed the complex spiroketal lactone core, and furnished EBC-23 and its C11 epimer. The C11 epimer was also converted to EBC-23 by chemoselective oxidation and reduction sequence. The present synthesis provides convenient access to this family of natural products in an efficient manner.",10.1021/acs.joc.1c00172,2021-04-19,0.6293673772811959
Organic Letters,Asymmetric Total Synthesis of Gracilamine and Determination of Its Absolute Configuration,"(+)-Gracilamine, a biologically attractive and structurally unique pentacyclic Amaryllidaceae alkaloid, was biomimetically synthesized in 11 linear steps in 9.9% overall yield from the known racemic oxocrinine. The synthesis features an asymmetric hydrogenation, a ring-opening/benzylic oxidation/cyclization sequence, and a biomimetic intramolecular cycloaddition. This total synthesis not only allows the assignment of its absolute configuration, but also provides experimental support for the hypothesis that naturally occurring (+)-gracilamine is biogenetically derived from the crinine-type alkaloid (+)-epivittatine.",10.1021/acs.orglett.7b02517,2017-09-28,0.6293358118056428
Tetrahedron,Practical route to D-manno and D-gluco azasugars from C2 symmetric bis-aziridines,,10.1016/0040-4039(96)01732-7,1996-10-01,0.6293231961102344
Green Chemistry,Utilizing biocatalysis and a sulfolane-mediated reductive acetal opening to access nemtabrutinib from cyrene,"The development of a protecting group-free, 2-step synthesis of 5-amino-2-hydroxymethyltetrahydropyran 1a from biorenewable Cyrene™ is described which renders access to BTK-inhibitor nemtabrutinib (2) more efficient and sustainable.",10.1039/d2gc04117k,2022-12-23,0.6293155334668322
Organic Process Research & Development,Economical Process for Preparation of the 19-nor A Ring of Paricalcitol from (−)-Shikimic Acid,"An economical and efficient means of preparing the 19-nor A ring, a key precursor of the vitamin D receptor (VDR) activator Paricalcitol, is here described. This process begins with commercially available (−)-shikimic acid and was easily scaled up to kilograms in a total yield over 17.8%. Davis oxidation was applied for the synthesis of the key precursor, α-hydroxyl carboxylic ester.",10.1021/acs.oprd.9b00209,2019-07-24,0.6293147920673458
Journal of the American Chemical Society,"The Catalytic Enantioselective, Protecting Group-Free Total Synthesis of (+)-Dichroanone","Herein we report the first enantioselective total synthesis of (+)-dichroanone, confirming the absolute configuration of the natural product. This protecting group-free route features the first application of our enantioselective Tsuji allylation in the context of a natural product total synthesis. Additionally, this 11-step preparation of the molecule from commercial material features a novel Kumada-aromatization strategy and a rapid sequence for the conversion of a phenol to a hydroxy-p-benzoquinone.",10.1021/ja061853f,2006-05-26,0.6292876193722924
Synthesis,Structure Elucidation and Enantioselective Total Synthesis of the HMG-CoA Reductase Inhibitors FR901512 and FR901516,"The enantioselective total synthesis of the potent HMG-CoA reductase inhibitors FR901512 (1) and FR901516 (2) is reviewed. FR901512 was prepared in 15 steps from commercially available compound via 2 in 16.3% overall yield (89% average yield). This study validated the applicability and reliability of the catalytic asymmetric Nozaki-Hiyama reactions that were developed by us. These reactions enabled the concise, efficient, and protecting-group-free enantioselective total syntheses of these new statins.",10.1055/s-0029-1216980,2009-08-28,0.6292841623364857
Organic Letters,An Expedient Total Synthesis of (−)-Dactylolide and Formal Synthesis of (−)-Zampanolide,[reaction: see text] A highly convergent and efficient total synthesis of (-)-dactylolide and formal synthesis of (-)-zampanolide is reported.,10.1021/ol0504897,2005-05-13,0.629269695788642
Angewandte Chemie International Edition,Concise Total Synthesis of (+)‐WIN 64821 and (−)‐Ditryptophenaline,"On a fast track: The secondary metabolites (+)-WIN 64821 and (−)-ditryptophenaline have been synthesized in six and seven steps, respectively, from amino acid derivatives in a concise and enantioselective manner. The gram-scale synthesis of key intermediates and the simultaneous introduction of vicinal quaternary stereocenters are described. The synthesis and structural confirmation of (−)-1′-(2-phenylethylene)ditryptophenaline is also reported.",10.1002/anie.200704960,2008-01-11,0.6292679394520155
Synthesis,An Efficient Route to Difluoromethylated Pyridines,A convenient route to difluoromethylated pyridines was developed that involves copper-promoted cross-coupling of halopyridines with ethyl difluoro(trimethylsilyl)acetate and subsequent decarboxylation.,10.1055/s-0032-1316761,2012-08-06,0.6292590599078418
Journal of Organic Chemistry,Expedient Five-Step Synthesis of SIB-1508Y from Natural Nicotine,"Altinicline (SIB-1508Y), an anti-Parkinson's agent, was prepared in five steps from natural nicotine in 32% overall yield via a regioselective substitution of the pyridine ring of (S)-nicotine.",10.1021/jo0616052,2006-10-01,0.6292547249878078
Synlett,"The Synthesis of 5,5-Disubstituted Piperidinones via a Reductive Amination–Lactamization Sequence: The Formal Synthesis of (±)-Quebrachamine",A preliminary investigation into the prospect of a common synthetic intermediate for the synthesis of a variety of indole alkaloids has led to a synthesis of substituted piperidinones and the corresponding piperidines. These common natural product cores are accessed via a reductive amination–lactamization sequence of dimethyl 3-ethyl-3-formylpimelate. The synthetic utility of this initial study has been displayed in the formal synthesis of (±)-quebrachamine.,10.1055/s-0034-1379986,2015-02-05,0.6292525413125184
Synthesis,"Development of a Practical Synthetic Method for Clinical Candidate 3-(2-{3-[(2,4-Diamino-6-ethylpyrimidin-5-yl)oxy]propoxy} phenyl)propanoic acid (P218) and Its Hydroxylated Metabolites","Abstract 3-(2-{3-[(2,4-Diamino-6-ethylpyrimidin-5-yl)oxy]propoxy}phenyl)propanoic acid, known as P218, has demonstrated great potency and safety in preclinical and human studies. However, the previous synthetic methods for P218 gave low yields and required hazardous reagents and challenging procedures. In this study, we have successfully developed a decagram-scale synthetic route for P218 with practical and scalable methods for large-scale production. Furthermore, this is also a first report of a novel synthetic approach for P218-OH, a hydroxylated metabolite of P218, by modification of our discovery route. Our synthetic procedures for P218 and P218-OH are a significant advancement in drug development processes, including manufacturing processes and drug metabolism studies.",10.1055/s-0042-1751502,2023-10-30,0.6292525375838575
Organic Letters,Concise Asymmetric Total Synthesis of 9-<i>epi</i>-Sessilifoliamide J,"A 10-step asymmetric synthesis of 9-epi-sessilifoliamide J (20), together with sessilifoliamide J (6), has been accomplished from the key chiral building block 11 via a threo-selective vinylogous Mannich reaction and a Ley oxidation-SmI(2)-mediated coupling lactonization. The absolute configuration of the natural sessilifoliamide J was established.",10.1021/ol202140y,2011-08-31,0.62924554915864
Journal of the American Chemical Society,Access to the Akuammiline Family of Alkaloids: Total Synthesis of (+)-Scholarisine A,"The planning and implementation of an enantioselective total synthesis of (+)-scholarisine A is presented. Key tactics employed include a novel cyclization, consisting of a nitrile reduction coupled with concomitant addition of the resultant amine to an epoxide; a modified Fischer indolization; an oxidative lactonization of a diol in the presence of an indole ring; and a late-stage cyclization to complete the caged ring scaffold. The development of a possible ""retro-biosynthetic"" approach to other members of the akuammiline alkaloid family is also described.",10.1021/ja3111626,2012-12-26,0.6292268281637116
Journal of Organic Chemistry,"Total Synthesis of (−)-5,6-Dihydrocineromycin B","An asymmetric total synthesis of (-)-5,6-dihydrocineromycin B has been accomplished in 13 steps from (-)-linalool O-triethylsilyl ether or 12 steps from geraniol. The present synthesis features (i) an intermolecular Wittig reaction involving an aldehyde possessing a ketophosphonate functionality and (ii) an intramolecular Horner-Wadsworth-Emmons olefination.",10.1021/jo802503x,2008-12-30,0.629209111224555
Tetrahedron,Novel and efficient synthesis of uracil phosphonate derivatives via pentacovalent oxaphospholenes,,10.1016/s0040-4039(00)77471-5,1993-02-01,0.6292029389990038
Tetrahedron,"Efficient synthesis of novel benzo-[e]-[1,4]-diazepine derivatives",,10.1016/s0040-4039(01)00402-6,2001-04-01,0.6292029389990038
Angewandte Chemie International Edition,Total Synthesis of Maoecrystal P: Application of a Strained Bicyclic Synthon,"Abstract A new strategy was devised for the total synthesis of highly oxidized ent ‐kauranoids. A highly regio‐ and diastereoselective intermolecular Diels–Alder cycloaddition involving a diene embedded in a substituted bicyclo[4.1.0] skeleton was used to assemble all carbon centers but C17 of the target molecule at an early stage of the synthesis. Subsequent synthetic steps, including redox manipulations, SmI 2 ‐mediated cyclization, and isomerization reactions, afforded the antitumor natural product maoecrystal P.",10.1002/anie.201711084,2017-12-05,0.6291895512649941
Organic Letters,Practical Synthesis of Quinoxalinones via Palladium-Catalyzed Intramolecular N-Arylations,A practical and highly efficient route to the synthesis of pharmaceutically interesting quinoxalinone scaffolds is reported. The key step involves an intramolecular palladium-catalyzed N-arylation under microwave irradiation. The developed methodology tolerates a variety of bromoanilides to afford a diverse collection of bicyclic and polycyclic quinoxalinones in high yield.,10.1021/ol101454x,2010-07-27,0.6291809800453617
Tetrahedron,A new synthesis of (±)-homosarkomycin ethyl ester,,10.1016/s0040-4039(00)02238-3,2001-02-01,0.6291733840547241
Journal of Organic Chemistry,The Thiopyran Route to Polypropionates:  Enantioselective Synthesis of Membrenone B from Racemic Fragments,"(6S,7S,8S,9R,10S)-(--)-Membrenone B was synthesized in nine steps (9.4% overall yield) beginning with two-directional aldol coupling of tetrahydro-4H-thiopyran-4-one with racemic 1,4-dioxa-8-thiaspiro[4.5]decane-6-carboxaldehyde. The first aldol reaction occurs with dynamic kinetic resolution to give a single adduct (>98% ee). The second aldol reaction is highly diastereoselective (three of eight possible adducts), and both major products are converted to membrenone B. The route also constitutes a formal synthesis of membrenone A.",10.1021/jo701546f,2007-09-01,0.6291648960475822
Tetrahedron,"A new route to 2,4-dibenzyltetrahydroquinoline. Reversibility of the homolytic aromatic benzylation.",,10.1016/s0040-4039(01)94997-4,1978-01-01,0.6291634872542436
Organic Letters,Synthesis of the Celogentin C Right-Hand Ring,"[reaction: see text] Synthesis of the cyclic tetrapeptide comprising the right-hand ring of celogentin C, a potent inhibitor of tubulin polymerization, has been accomplished. A mild oxidative coupling reaction permitted construction of the indole-imidazole linkage via a convergent union of two fully functionalized dipeptides. A high-yielding macrolactamization and subsequent deprotection of the N-terminus furnished the target compound.",10.1021/ol060016f,2006-02-24,0.6291603026170377
Journal of the American Chemical Society,Enantioselective Total Synthesis of (+)-Psiguadial B,"The first enantioselective total synthesis of the cytotoxic natural product (+)-psiguadial B is reported. Key features of the synthesis include (1) the enantioselective preparation of a key cyclobutane intermediate by a tandem Wolff rearrangement/asymmetric ketene addition, (2) a directed C(sp(3))-H alkenylation reaction to strategically forge the C1-C2 bond, and (3) a ring-closing metathesis to build the bridging bicyclo[4.3.1]decane terpene framework.",10.1021/jacs.6b07229,2016-07-24,0.6291536144553943
Organic Letters,Total Synthesis and Stereochemical Revision of Biemamides B and D,"The first expedient asymmetric synthesis of both enantiomers of 5,6-dihydrouracil-type marine natural products biemamides B and D was achieved from chiral 1-(α-methylbenzyl)aziridine-2-carboxylate. The key steps involved in the synthetic route are regio- and stereoselective aziridine ring opening via azide followed by a base-induced cyclization reaction. After comparison of ECD and optical rotation data of both synthetic enantiomers, the absolute configuration of natural biemamides B and D at the C5 position has been assigned as (−)-(5 S ), which is an enantiomer to the originally proposed structure (−)-(5 R ).",10.1021/acs.orglett.9b03394,2019-10-22,0.6291180851479232
Journal of Organic Chemistry,A Biomimetic Approach for Construction of an Advanced Intermediate en Route to Melicolones A and B,"A biomimetic approach for the synthesis of an advanced intermediate en route to melicolones A and B is described, leading to successful construction of the crucial bicyclo[3.2.1]octane carbon framework of these molecules. Key steps of the strategy include a Wolff rearrangement, a titanium-mediated Giese-type cyclization, and a nitrone acylation/rearrangement process. Our approach enables the reliable assembly of a fully functionalized tricyclic precursor, which in turn provides valuable handles for further elaboration of the target molecules.",10.1021/acs.joc.5c00734,2025-05-22,0.6291158990147138
Synthesis,Synthesis of the 5-Fluoro-4-hydroxypentyl Side Chain Metabolites of Synthetic Cannabinoids 5F-APINACA and CUMYL-5F-PINACA,An efficient method for the construction of the 5-fluoro-4-hydroxypentyl side chain common to a number of synthetic cannabinoid metabolites was developed. A series of hydroxyl protecting groups was examined to assess the viability as orthogonal protecting groups for epoxidation and regioselective hydrofluorination. The 1-[5-fluoro-4-(diphenyl-tert-butylsilyloxy)]pentyl tosylate was prepared in 67% overall yield (six steps) from pent-4-en-1-ol and was employed for the synthesis of the 4-hydroxy metabolites of the synthetic cannabinoid 5F-APINACA and CUMYL-5F-PINACA.,10.1055/s-0037-1609914,2018-08-14,0.6291156911510768
Journal of Organic Chemistry,Synthesis of CBD and Its Derivatives Bearing Various C4′-Side Chains with a Late-Stage Diversification Method,"A novel synthetic route for making (-)-CBD and its derivatives bearing various C4'-side chains is developed by a late-stage diversification method. Starting from commercially available phloroglucinol, the key intermediate (-)-CBD-2OPiv-OTf is efficiently and regioselectively prepared and further undergoes Negishi cross-coupling to furnish (-)-CBD. This approach allowed an efficient synthesis of (-)-CBD in a five-step total 52% yield on a 10 g scale. Furthermore, diversification on the C4'-side chain with this method can be realized in a wide range.",10.1021/acs.joc.9b02880,2019-12-30,0.6291028446053073
Journal of Organic Chemistry,Synthetic Entry into 1-Phosphono-3-azabicyclo[3.1.0]hexanes,"3-Azabicyclo[3.1.0]hex-2-en-1-yl phosphonates were prepared in a five-step reaction route from β-ketophosphonates. The key steps in this sequence are an atom-transfer radical cyclization and an unforeseen lithium-halogen exchange with n-BuLi. The cyclization reaction proceeds with excellent diastereoselectivity. The resulting cyclic imines were reduced, and 3-azabicyclo[3.1.0]hexan-1-yl phosphonates were obtained.",10.1021/jo401185u,2013-08-21,0.6290977262678763
Journal of the American Chemical Society,"Synthesis of (.+-.)-7,8-Epoxy-4-basmen-6-one by a Transannular Cyclization Strategy","The first synthesis of the cembranoid natural product (±)-7,8-epoxy-4-basmen-6-one (1) is described. Key steps of the synthetic route include the cationic cyclization of the acid chloride from 15 to provide the macrocycle 16, and the photochemical transannular radical cyclization of the ester 41 to form the tricyclic product 50. Product 50 was transformed into 1 in ten steps. Transition-state molecular modeling studies were found to provide accurate predictions of the structural and stereochemical outcomes of cyclization reactions explored experimentally in the development of the synthetic route to 1. These investigations should prove valuable in the development of transannular cyclization as a strategy for synthetic simplification.",10.1021/ja00116a012,1995-03-01,0.6290838867248173
Synthesis,"An Efficient One-Pot Synthesis of Oxetanes from 1,3-Diols",,10.1055/s-1981-29523,1981-01-01,0.6290770107151022
Tetrahedron,Efficient synthesis of tricyclic quinazolines by one-pot cyclizations of 2-(dichloroisocyanido)benzonitrile,,10.1016/j.tetlet.2004.09.125,2004-10-05,0.6290770107151022
Tetrahedron,Efficient one-pot synthesis of 1-alkoxy-2-arylaminoimidazolines from N-alkoxy-N-(2-aminoethyl)-2-nitrobenzenesulfonamides and arylisothiocyanates,,10.1016/j.tetlet.2008.05.098,2008-05-29,0.6290770107151022
Tetrahedron,Efficient one-pot synthesis of glycosyl disulfides,,10.1016/j.tetlet.2007.08.106,2007-09-05,0.6290770107151022
Tetrahedron,An efficient one-pot synthesis of bisalkylthioarenes,,10.1016/j.tetlet.2003.11.015,2003-12-04,0.6290770107151022
Tetrahedron,An efficient one-pot synthesis of (+)-deoxypyridinoline,,10.1016/s0040-4039(99)01936-x,1999-12-01,0.6290770107151022
Tetrahedron,An efficient one-pot synthesis of flavones,,10.1016/j.tetlet.2011.04.022,2011-04-18,0.6290770107151022
Tetrahedron,"An efficient one-pot synthesis of functionally diverse 2-aminothiazoles from isothiocyanates, amidines/guanidines and halomethylenes",,10.1016/j.tetlet.2013.07.122,2013-07-31,0.6290770107151022
European Journal of Organic Chemistry,Towards the Total Synthesis of the Norsesterterpene Diacarnoxide C,The synthesis of the norsesterterpene diacarnoxide C was achieved. The endoperoxide moiety could be prepared in nine and the norsesquiterpene moiety in five steps starting from ( E )‐3‐methyl‐6‐oxohex‐2‐en‐1‐yl acetate and dihydro‐β‐ionone. The peroxide aldehyde and the norsesquiterpene sulfone were coupled in an ( E )‐selective Julia–Kocienski reaction. The coupling product was transformed in three additional steps to an inseparable mixture of diacarnoxide C and three further isomers.,10.1002/ejoc.201700922,2017-09-28,0.6290733859006082
Journal of Organic Chemistry,Convenient Route to Both Enantiomers of a Highly Functionalized Trans-Disubstituted Cyclopentene. Synthesis of the Carbocyclic Core of the Nucleoside BCA,"[structures: see text] Synthesis of both enantiomers of a highly functionalized cyclopentenol derivative, versatile building block for a vast array of biologically active compounds, is described. The key steps involve stereocontrolled synthesis of a diene with two syn-disposed substituents from a (R)-(+)-glyceraldehyde derivative, ring-closing metathesis of this diene, and functional group manipulation of the resulting trans-disubstituted cyclopentene. One of the enantiomers of the cyclopentenol thus obtained has been converted to an amino cyclopentene, the carbocyclic core of the nucleoside (-)-BCA, a potent inhibitor of HIV reverse transcriptase.",10.1021/jo0502504,2005-04-05,0.6290709020195732
Organic Letters,Asymmetric Synthesis of an Advanced Tetracyclic Framework of (+)-Sarain A,"An asymmetric synthetic approach to a tetracyclic framework of the marine-derived alkaloid (+)-sarain A has been developed. The key steps to constructing the congested diazatricycloundecane core include an asymmetric Diels-Alder cycloaddition, an Ireland-Claisen rearrangement, and an intramolecular aziridination/ring-opening sequence.",10.1021/acs.orglett.8b02779,2018-10-22,0.6290613021511087
Journal of Organic Chemistry,Asymmetric Total Synthesis of (+)-Virosine A via Sequential Nucleophilic Cyclizations onto an Activated Formamide,"The first synthesis of tetracyclic alkaloid virosine A is reported. The natural alkaloid was prepared in only 13 steps, in an enantioenriched form. The azabicyclo[2.2.2]octane core was efficiently assembled using a key Vilsmeier-Haack and Mannich cyclizations sequence performed in one pot.",10.1021/jo202651t,2012-03-06,0.6290550475618971
Angewandte Chemie International Edition,Total Synthesis of Kopsinitarine E,"Abstract Kopsinitarines A–E are complex octacyclic caged Kopsia alkaloids with strained cage skeletons and a unique cyclic hemiaminal bridge that makes total synthesis challenging. Herein, we disclose the first total synthesis of kopsinitarine E. The key synthetic features include a SmI 2 ‐mediated radical cascade cyclization and a subsequent semi‐pinacol rearrangement to install the key carbocyclic skeleton, a chemoselective hydrosilyl amide reduction to construct the hemiaminal ether bridge, and an intramolecular Mannich reaction to establish the highly strained cage system.",10.1002/anie.202011093,2020-08-25,0.6290522875035551
Synthesis,An Expedient Asymmetric Synthesis of a Calystegine B<sub>4</sub>Analogue,"A convenient, high-yielding synthetic route to polyhydroxylated 6-oxa-nor-tropanes that mimic the structural framework of calystegine B4 is reported.",10.1055/s-2002-33706,2002-01-01,0.6290201389461189
Journal of Organic Chemistry,Synthesis of 2-(1<i>H</i>-Indol-2-yl)acetamides via Brønsted Acid-Assisted Cyclization Cascade,"An efficient and straightforward Brønsted-acid mediated cascade process was developed, involving cyclization of readily available β-ketonitriles into 2-aminofurans, and their subsequent recyclization into 2-(1 H -indol-2-yl)acetamides is developed. This synthetic route opens a new avenue for an expeditious assembly of various isotryptamine derivatives for medicinal chemistry.",10.1021/acs.joc.0c01344,2020-09-03,0.629019006832057
Synthesis,"Stereoselective Synthesis of (10S,12S)-10-Hydroxy-12-methyl-1-oxacyclododecane-2,5-dione via Prins Cyclization","The total synthesis of (10S,12S)-10-hydroxy-12-methyl-1-oxacyclododecane-2,5-dione is described proving the versatility of the Prins cyclization in natural products synthesis. The approach is convergent and highly stereoselective. Prins cyclization, esterification, ring-closing metathesis and oxidation reactions are utilized as key steps in the synthesis of this macrolactone.",10.1055/s-0029-1217107,2009-11-24,0.6290104971570639
Organic Letters,"Effective Strategy for the Preparation of Indolocarbazole Aglycons and Glycosides:  Total Synthesis of Tjipanazoles B, D, E, and I","[reaction: see text] An effective strategy has been developed for the rapid and efficient preparation of ortho-nitrostyrenes, which can be converted to unsymmetrical 2,2'-biindoles. A unique condensation of these 2,2'-biindoles with (dimethylamino)-acetaldehyde diethyl acetal affords the indolocarbazole ring system of the tjipanazole aglycon alkaloids in three synthetic steps and good to excellent overall yield. The first total synthesis of the tjipanazole glycoside alkaloids B and E is also discussed.",10.1021/ol035418r,2003-09-03,0.6290018055522832
Tetrahedron,A new synthesis of the california red scale pheromone from s-(+)-carvone,,10.1016/s0040-4039(01)91283-3,1984-01-01,0.628992255495198
European Journal of Organic Chemistry,On the Way to Glycoprocessing Inhibitors − Synthesis of an Imidazolo‐Nectrisine‐Phosphono Acid Derivative: A Potential Glycosyltranferase Inhibitor,"Abstract Assuming the transition state of glycosyltransferase inhibitors to be similar to those encountered with potent glycosidase inhibitors − i.e. a flattened conformation with a positively charged anomeric centre − we worked out a synthesis of the D ‐ arabino ‐configured phosphonic acid target molecule 2 derived from an imidazolo‐sugar. The key synthetic intermediate is the linear imidazolo L ‐ xylo compound 10 which could be obtained, either from L ‐ threo precursor 6 by a coupling reaction with imidazole derivative 5 , or from L ‐sorbose. A multi‐step and site specific iodination of 10 gave the mono‐iodo‐ L ‐ xylo derivative 14 which was cyclised to the D ‐ arabino ‐configured bicyclic azasugar 15 . Phosphorylation of the Grignard derivative of the latter, followed by mono‐esterification with citronellol along with some protection‐deprotection steps led to target molecule 2 . The potential inhibitor 2 is supposed to be protonated at its most basic N atom by a carboxylic acid residue in the arabinosyl‐transferase active site. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2003)",10.1002/ejoc.200300190,2003-07-15,0.6289809919688898
Journal of Organic Chemistry,An Efficient Synthesis of (±)-Dehaloperophoramidine,"Perophoramidine and communesin F are structurally related indole alkaloids with an intriguing polycyclic core containing vicinal all-carbon quaternary stereocenters. Dehaloperophoramidine is a dehalogenated synthetic analogue of perophoramidine. Synthetic studies toward the total synthesis of dehaloperophoramidine have led to the discovery of two novel domino processes, the first encompassing four steps and resulting in the formation of an ortho-amide. A thorough study of the reactivity of the ortho-amide functionality revealed the second domino reaction and ultimately yielded the target molecule. The vicinal all-carbon quaternary stereocenters having trans relative stereochemistry are constructed early in the reaction sequence by employing Overman's samarium mediated reductive dialkylation procedure. Described are the synthetic studies that led to the final eight-step synthesis of dehaloperophoramidine.",10.1021/acs.joc.6b02969,2017-02-01,0.62897876514432
Organic Letters,"A New Stereocontrolled Total Synthesis of the Mast Cell Inhibitory Alkaloid, (+)-Monanchorin, via the Wittig Reaction of a Stabilized Ylide with a Cyclic Guanidine Hemiaminal","An asymmetric total synthesis of the mast cell inhibitor (+)-monanchorin is reported in which a Sharpless AD on 11 and a cyclic sulfate ring opening with an azide feature as key steps. After further manipulation, a novel guanidine-controlled ester reduction provided the guanidine-hemiaminal 25 which underwent Wittig olefination to give 27. Hydrogenation and a second guanidine-controlled reduction of the ester in 28, to obtain aldehyde 29, then set up a trifluoroacetic acid mediated cyclization to give (+)-monanchorin TFA salt.",10.1021/ol500616v,2014-04-07,0.628973214000071
Chemical Science,Divergent total syntheses of pyrroloiminoquinone alkaloids enabled by the development of a Larock/Buchwald–Hartwig annulation/cyclization,"Pyrroloiminoquinone alkaloids are a large class of natural products that display a wide range of biological activities. Synthetic approaches to these natural products typically rely on a common late-stage C10-oxygenated pyrroloiminoquinone intermediate, but these strategies often lead to lengthy synthetic sequences that are not amenable to divergent syntheses. We devised an alternative approach aimed at the early introduction of the C10 nitrogen, which we hypothesized would enable late-stage diversification. This strategy hinged upon a Larock/Buchwald-Hartwig annulation/cyclization to quickly access the core of these alkaloids. We report the development of this cascade process, which was facilitated by a dual ligand system in addition to selective functionalization of the key intermediate, to provide efficient syntheses of makaluvamines A, C, and D and isobatzelline B, and the first total synthesis of makaluvamine N.",10.1039/d4sc02981j,2024-01-01,0.6289619646138154
Synthesis,Synthetic Approach for Constructing the 1-Oxygenated Carbazole Core and Its Application to the Preparation of Natural Alkaloids,"An efficient synthetic approach for the construction of the 1-oxygenated carbazole core is described. The condensation of cyclohexane-1,2-diones with a series of anilines yielded the corresponding 2-anilinocyclohex-2-en-1-ones, followed by the one-pot aromatization/methylation process of the latter to provide N -aryl-2-methoxyanilines. A palladium(II)-catalyzed cyclization of these N -aryl-2-methoxyanilines afforded the desired 1-methoxycarbazole frame in high overall yields. This protocol was implemented for the total synthesis of the naturally occurring glycozolicine and 6-meth­oxymurrayanine.",10.1055/s-0032-1317175,2012-08-23,0.6289581440447395
Organic Process Research & Development,"Process Research for (+)-Ambrisentan, an Endothelin-A Receptor Antagonist",An efficient and robust synthetic route to (+)-ambrisentan ((+)-AMB) was designed by recycling the unwanted isomer from the resolution mother liquors. The racemization of AMB in the absence of either acid or base in the given solvents was reported. The recovery process was developed to produce racemates with purities over 99.5%. The mechanism of the formation of the process-related impurities of (+)-AMB is also discussed in detail. (+)-AMB was obtained in 47% overall yield with >99.5% purity and 99.8% e.e. by chiral resolution with only one recycling of the mother liquors on a 100-g scale without column purification.,10.1021/acs.oprd.8b00184,2018-08-06,0.6289454743877115
Organic Letters,Enantioselective Total Synthesis of Spirofungins A and B,The enantioselective total synthesis of spirofungins A (1) and B (2) is reported in 14 steps over the longest linear sequence. Key steps include the use of thiazolidinethione-mediated aldol reactions to assemble the major fragments and installation of the C1-C6 side chain using a cross metathesis reaction.,10.1021/ol101961c,2010-09-10,0.6289401365977774
Journal of Organic Chemistry,Synthesis of the Lipophilic Antifolate Piritrexim via a Palladium(0)-Catalyzed Cross-Coupling Reaction,"[reaction: see text] A regiospecific and convergent route the lipophilic antifolate piritrexim (PTX) is described in which a key step is a Pd(0)-catalyzed cross-coupling reaction between 2-amino-3-cyano-4-methyl-5-bromopyridine and 2,5-dimethoxybenzylzinc chloride to form 2-amino-4-methyl-5-(2,5-dimethoxybenzyl)nicotinonitrile. To complete the synthesis, the amino group is replaced by a more reactive bromine atom via nonaqueous diazotization with tert-butyl nitrite, and the resultant bromo nitrile is cyclized with guanidine.",10.1021/jo040268z,2005-01-21,0.6289386167904134
Journal of Organic Chemistry,[4 + 2]-Annulations of Chiral Organosilanes:  Application to the Total Synthesis of Leucascandrolide A,"Complete details of an asymmetric synthesis of leucascandrolide A (1) are described. The synthesis highlights the use of two diastereoselective [4 + 2]-annulations for the assembly of the functionalized bispyranyl macrolide 3. An efficient assembly and union of the oxazole-containing side chain 4 with macrolide 3 was carried out using a Mitsunobu reaction. A convergent route to the oxazole side chain was developed using a Sonogashira cross-coupling between 2-trifloyloxazole 16 and alkyne 17, which allowed for the installation of the C9'-C10' (Z)-olefin.",10.1021/jo0610412,2006-09-01,0.6289230367911776
European Journal of Organic Chemistry,"Efficient Synthesis of (1,2,3‐Triazol‐1‐yl)methylpyrimidines from 5‐Bromo‐1,1,1‐trifluoro‐4‐methoxypent‐3‐en‐2‐one","5‐Bromo‐1,1,1‐trifluoro‐4‐methoxypent‐3‐en‐2‐one was used as an efficient precursor for the synthesis of a new series of (1,2,3‐triazol‐1‐yl)methyl‐pyrimidine biheterocycles. For this stepwise synthesis, the 5‐bromo‐1,1,1‐trifluoro‐4‐methoxypent‐3‐en‐2‐one was first converted into 5‐azido‐1,1,1‐trifluoro‐4‐methoxypent‐3‐en‐2‐one through a nucleophilic substitution of the bromine by an azide group. This was then followed by an azide–alkyne cycloaddition reaction (click chemistry) to give the key intermediate 5‐[4‐alkyl(aryl)‐1 H ‐1,2,3‐triazol‐1‐yl]‐1,1,1‐trifluoro‐4‐methoxypent‐3‐en‐2‐ones. These were cyclocondensed with 2‐methylisothiourea sulfate to give a series of 2‐(methylthio)‐4‐(1,2,3‐triazol‐1‐yl)methyl‐6‐(trifluoromethyl)pyrimidines. Additionally, the 2‐methylthiopyrimidine products were used to prepare a new series of 2‐amino‐4‐(1,2,3‐triazol‐1‐yl)methyl‐6‐(trifluoromethyl)pyrimidines.",10.1002/ejoc.201601234,2016-10-26,0.6289200869993167
European Journal of Organic Chemistry,"Asymmetric Synthesis of δ‐Chloro‐β‐amino‐<i>N</i>‐sulfinyl Imidates as Versatile Chiral Building Blocks for the Synthesis of 2,3‐Disubstituted Piperidines",Abstract Mannich‐type reactions of chiral δ‐chloro‐ N ‐ tert ‐butanesulfinyl‐substituted imidates across N ‐sulfonyl aldimines resulted in the efficient and anti ‐stereoselective synthesis of new β‐(sulfonylamino)‐ N ‐sulfinyl imidates ( dr &gt; 99:1). These compounds were then successfully cyclized to give 2‐aryl‐ N ‐sulfonylpiperidine‐3‐( N ‐sulfinyl)carbimidates in high yields. These proved to be useful intermediates for the synthesis of chiral methyl 2‐arylpiperidine‐3‐carboxylates as well as cis ‐3‐amino‐2‐aryl‐ N ‐sulfonylpiperidines.,10.1002/ejoc.201500466,2015-06-22,0.6289165691918597
Angewandte Chemie International Edition,Inside Back Cover: A Convergent Total Synthesis of the Telomerase Inhibitor (±)‐γ‐Rubromycin (Angew. Chem. Int. Ed. 17/2014),"Silicon in, silicon out could be the caption for the convergent total synthesis of the telomerase inhibitor (±)-γ-rubromycin reported by M. Wilsdorf and H.-U. Reissig in their Communication on page 4332 ff. They combine three highly functionalized building blocks through selective organometallic chemistry and a silyl-substituted C3 building block plays a key role. Three acid-promoted reactions serve to generate the sensitive spiroketal natural product under desilylation. Graphic courtesy of Dr. Daniel Trawney.",10.1002/anie.201401119,2014-04-01,0.6289097632014418
Tetrahedron,"Alternative synthesis of α-substituted β-amidophosphines by [1,4]-addition. A new route to chiral ligands",,10.1016/s0040-4039(02)02250-5,2002-12-01,0.6288916663460913
Tetrahedron,"Synthesis and rearrangement of diaryl-hydroxy-benzo[b]thiophens. A new synthesis of 2,3-diaryl-benzo[b]thiophens.",,10.1016/s0040-4039(00)86275-9,1983-01-01,0.6288835117773652
Organic Letters,The First Synthesis of a Thioglycoside Analogue of the Immunostimulant KRN7000,"The first total synthesis of a thioglycoside analogue of KRN7000, a potential immunostimulant, is described. Two key intermediates are alpha-galactosyl thiol 4 and phytosphingosine derivative 5, which were both prepared from D-galactose.",10.1021/ol8019555,2008-09-23,0.6288768790306966
Organic Process Research & Development,"Selection and Scale-Up Evaluation of an Alternative Route to (−)-(3<i>R</i>,4<i>R</i>)-1-Benzyl-4-(benzylamino)piperidin-3-ol","An efficient, scalable synthesis of (−)-(3 R,4 R )-1-benzyl-4-(benzylamino)piperidin-3-ol ( 4 ) is described. Reduction of the pyridinium salt prepared from pyridine and benzyl chloride generated the corresponding tetrahydropyridine derivative. A two-stage epoxidation, followed by ring-opening of the epoxide with BnNH 2, established the regiochemistry of the amino alcohol and served to set the trans -relationship between the amine and the hydroxyl group. The resulting racemic intermediate was then resolved by salt formation with ( R )- O -acetyl mandelic acid. The process produced the O -acetyl mandelic acid salt of (−)- 4 in 27% overall yield from benzyl chloride.",10.1021/op300174w,2012-09-06,0.6288633858794401
Tetrahedron,"A novel synthesis of (±)-2-acetyl-5,8-dimethoxy-1,2,3,4-tetrahydro-2-naphthol, a key intermediate for the synthesis of anthracyclinones",,10.1016/s0040-4039(00)78596-0,1980-01-01,0.6288558086889435
Organic Process Research & Development,Scale-Up Synthesis of Swainsonine: A Potent α-Mannosidase II Inhibitor,"The large-scale synthesis of Swainsonine 1, a potent α-mannosidase II inhibitor, has been achieved with several improvements. The key modifications were (a) performing the Wittig olefination under mild conditions and isolation of the product 4 with modified workup conditions, (b) introduction of the azido group on a large scale under Mitsunobu conditions to produce 12, (c) performing the 1, 3-dipolar cycloaddition of an unactivated azide 12 to afford the imino carboxylic ester 7, (d) formation of amide 10 from 7 under mild acidic conditions, and (e) isolation of the final compound 1 as a stable hydrochloride salt. In addition, synthesis of 11 was accomplished from 12 by telescoping the four steps.",10.1021/op800059y,2008-07-26,0.6288460763319778
European Journal of Organic Chemistry,Total Synthesis and Antibiotic Properties of Amino‐Functionalized Aromatic Terpenoids Related to Erogorgiaene and the Pseudopterosins,"Abstract Following a concept recently introduced by Hergenrother , [6] the present study addresses the question of whether certain antimicrobially active aromatic (marine) natural products can be converted into more potent broad‐spectrum antibiotics by introducing an aminoalkyl side chain. To this end, phenolic mono‐ and sesquiterpenoids (incl. carvacrol, xanthorrhizol, and 7‐hydroxycalamene) as well as the diterpenes 7‐hydroxyerogorgiaene and 9‐deoxypseudopterosin A were converted into amino‐functionalized analogs that display either an amino‐methyl or a 2‐amino‐ethoxy substituent in place of (or next to) the OH group. This was achieved either by Pd‐catalyzed nitromethylation/reduction of the aryltriflates, by O ‐alkylation of the phenols with bromoacetonitrile and subsequent reduction, or by ortho ‐hydroxymethylation/amination. During the study, an efficient enantioselective total synthesis of 7‐hydroxyerogorgiaene (8 steps, 29 % overall yield) and 9‐deoxypseudopterosin A (9 steps, 30 % overall yield) was elaborated using an asymmetric cobalt‐catalyzed hydrovinylation (91 % ee ) of 3‐methoxy‐4‐methyl‐styrene as the chirogenic step. Other important C−C bond forming steps include a Pd‐catalyzed Suzuki cross‐coupling and diastereoselective Lewis acid‐mediated cyclization reactions. A total of 16 amino derivatives of natural products were prepared and subsequently tested for their antibacterial properties. Some of the diterpene‐derived amines showed high efficacy, not only against Gram‐positive ( S. aureus SG511 , S. aureus HG003 , B. subtilis 168; MIC=0.5 to 2 μg/ml), but also against Gram‐negative bacterial strains ( E. coli K12; E. coli I‐11276b; MIC=8 to 32 μg/ml). This clearly supported the underlying working hypothesis.",10.1002/ejoc.202200058,2022-01-27,0.6288367962689895
Organic Process Research & Development,Process Development of the Soft Histone Deacetylate Enzyme Inhibitor SHP-141: Acylation of Methyl Paraben and Suberyl Hydroxamic Acid Formation,"SHP-141 ( 1 ) is a hydroxamic acid-based inhibitor of histone deacetylase enzymes which is under development for the treatment of cutaneous T-cell lymphoma. The original synthesis of 1 involved five synthetic steps beginning with suberic acid monomethyl ester. Final deprotection of the O -benzyl hydroxamate moiety using hydrogen and palladium catalyst mandated the use of metal scavengers to reduce palladium levels to within International Council for Harmonisation (ICH) guidance. Owing to the sensitivity of 1 toward self-condensation and the potential for N–O bond cleavage under hydrogenolytic conditions, we developed an alternative route to 1 which avoids Pd-mediated hydrogenation and prolonged metal scavenger treatment. This two-step process employs readily available suberic acid and methyl paraben and has successfully delivered multiple kilograms of 1 for clinical use. Importantly, crude 1 was stabilized for recrystallization in acetonitrile (ACN) solution by the addition of 0.1% citric acid and 4% water. Additionally, the filtration and drying of suitably sized aggregates of 1 with high purity (100 area%) was accomplished via temperature cycling of the 1 /ACN solution.",10.1021/acs.oprd.6b00280,2016-09-19,0.6288332395072994
Journal of Organic Chemistry,Regioselective and Stereoselective Reductive Aziridinium Ring Cleavage Leading to Azabicyclodecane Architecture: Enantioselective Synthesis of (+)-Subincanadine F,"Enantioselective synthesis of cytotoxic indole alkaloid (+)-subincanadine F was accomplished starting from the corresponding ( S)-acetoxysuccinimide via aziridinium ring formation and its reductive ring expansion route. Regioselective and stereoselective reductive aziridinium carbon-nitrogen bond cleavage comprising ring expansions was a key step. The ( S)-OMOM protection of the hydroxyl moiety adjacent to a benzylic carbon of an in situ formed aziridinium system was necessary for lithium borohydride-induced reductive ring expansions, and it also served as a latent source of an essential ketone carbonyl group for the generation of an α,β-conjugated system.",10.1021/acs.joc.8b02113,2018-08-30,0.6288222617076068
European Journal of Organic Chemistry,The First Enantioselective Approach to 13a‐Methyl‐14‐hydroxyphenanthroindolizidine Alkaloids – Synthetic Studies towards Hypoestestatin 2,"Abstract The first enantioselective approach to 13a‐methyl‐14‐hydroxyphenanthroindolizidine alkaloids was achieved in six linear steps from phenanthryl alcohol and features a highly substrate‐dependent Parham cycloacylation and Seebach's enantioselective alkylation as the key steps. The route is concise, protecting‐group free, provides access to all stereoisomers, and works on a gram scale. In addition to the putative structure of hypoestestatin 2, the other three stereoisomers and two structurally related analogues were synthesized, none of which shows identical NMR spectra to those reported for natural hypoestestatin 2, which indicates that further structure revision is required.",10.1002/ejoc.201201472,2013-02-11,0.628809991289276
Organic Process Research & Development,Manufacturing Process for HIF-2α Inhibitor Casdatifan (AB521): Creating Five Chiral Centers with High Stereoselectivity,"A manufacturing process for HIF-2α inhibitor casdatifan suitable on a multikilogram scale and beyond is presented. Key features include the convergent coupling of two fragments ( A7 and B4 ) of similar complexity, followed by diastereoselective olefin hydrogenation to introduce the tetralin central C-8 chiral center of intermediate C4 . Double electrophilic alpha fluorination of the diketone C4, followed by double Noyori transfer hydrogenation enables the introduction of the additional four chiral centers to produce the penultimate diol intermediate C6 . Chemo and stereoselective deoxyfluorination of one of the two benzylic alcohols produces casdatifan.",10.1021/acs.oprd.5c00214,2025-09-03,0.628802399951059
Journal of Organic Chemistry,"Enantioselective Synthesis of (2<i>R</i>,4<i>S</i>)- and (2<i>S</i>,4<i>R</i>)-4-Hydroxypipecolic Acid from <scp>d</scp>-Glucoheptono-1,4-lactone","Enantiomerically pure (2 R,4 S )-4-hydroxypipecolic acid [(+)- 1 ] was synthesized from d -glucoheptono-1,4-lactone ( 2 ) via the 3,5-dideoxy- d - xylo -heptono-1,4-lactone ( 7 ). The latter was readily prepared by benzoylation of 2, followed by β-elimination and diastereoselective hydrogenation of the resulting furanones ( 4 ). Compound 7 was converted into the 6,7- O -cyclohexylidene derivative 11, which on treatment with tosyl chloride for long periods afforded the 2-chloro derivative 14, the precursor of the azide 15 . Hydrogenolysis of 15 and protection of the amine gave the N -benzyloxycarbonyl derivative 19, having the required configuration for the stereocenters at C-2 and C-4. Removal of the cyclohexylidene group by hydrolysis and subsequent oxidative degradation of the resulting glycol system afforded the hexurono-6,3-lactone 21 as a key intermediate. Chemoselective reduction of the aldehyde function of 21 led to the alcohol 23, which was derivatized as the mesylate 24 . Releasing of the amino group by hydrogenation, and dissolution of resulting 25 in aqueous alkali, promoted the intramolecular nucleophilic displacement of the mesylate to give (+)- 1 . Its enantiomer [(−)- 1 ] was prepared by a similar sequence starting from 2 .",10.1021/jo990445+,1999-07-29,0.6288004650486473
Organic Letters,Total Synthesis of (+)-Peloruside A,"[reaction: see text] A total synthesis of (+)-peloruside A has been successfully achieved. The strategy was highlighted by a late stage aldol coupling of two complex fragments followed by an intramolecular hemi-ketal cyclization, a MOM group participated epoxide ring fragmentation reaction, and a highly selective methylation. This convergent route allows access to rationally designed analogues.",10.1021/ol050070g,2005-03-01,0.6287938425722703
Journal of Organic Chemistry,Synthesis of the Putative Structure of 15-Oxopuupehenoic Acid,"Synthesis of the putative structure of the marine natural 15-oxopuupehenoic acid has been achieved starting from commercial (-)-sclareol. Key steps of the synthetic sequence are the Robinson annulation of a β-ketoester and methyl vinyl ketone and an unprecedented cyclization of the resulting α,β-enone, which is mediated by tin(IV) chloride in the presence of N-phenylselenophthalimide. The physical properties of the synthetic compound are somewhat different from those reported for the natural product.",10.1021/jo502048y,2014-10-02,0.6287877696179168
Journal of the American Chemical Society,"Total Synthesis of Enigmazole A from <i>Cinachyrella enigmatica</i>. Bidirectional Bond Constructions with an Ambident 2,4-Disubstituted Oxazole Synthon","The first total synthesis of the cytotoxic marine macrolide enigmazole A has been completed in 22 steps (longest linear sequence). The sensitive, densely functionalized 2,4-disubstituted oxazole fragment was constructed using an efficient Negishi-type coupling of an oxazol-2-ylzinc reagent formed directly from the parent ethyl 2-iodooxazole-4-carboxylate by zinc insertion. Other key steps include a hetero-Diels-Alder cycloaddition to form the central embedded pyran ring, a Wittig reaction to unite Eastern and Western hemispheres, and a ring size-selective Keck macrolactonization.",10.1021/ja1016975,2010-06-30,0.6287735705145404
Tetrahedron,Nucleophilic attack on 2-(4-oxoalkyl)-2-imidazolines: a novel route to tetrahydropyridines and piperidines,,10.1016/s0040-4039(01)93788-8,1989-01-01,0.6287723515090383
Tetrahedron,"Concise asymmetric routes to 2,2,4-trisubstituted tetrahydrofurans via chiral titanium imide enolates: Key intermediates towards synthesis of highly active azole antifungals SCH 51048 and SCH 56592",,10.1016/0040-4039(96)01203-8,1996-08-01,0.6287666007171724
Journal of Organic Chemistry,"Step-Economical Synthesis of the Marine Ascidian Antibiotics Cadiolide A, B, and D","A concise, modular and efficient synthesis of the title natural products is reported. Prominent steps include (i) one-pot assembly of a key β-aryl-α-benzoylbutenolide building block by regiocontrolled ""click-unclick"" oxazole-ynone Diels-Alder cycloaddition/cycloreversion and ensuing 2-alkoxyfuran hydrolysis and (ii) a protecting group-free vinylogous Knoevenagel condensation enabling rapid access to cadiolides A, B, and D from a common precursor.",10.1021/jo502503w,2014-11-25,0.6287663558948287
Journal of Organic Chemistry,"Enantioselective Synthesis of the Excitatory Amino Acid (1<i>S,</i>3<i>R</i>)-1-Aminocyclopentane-1,3-dicarboxylic Acid","An enantioselective synthesis of the alpha,alpha-dialkyl-alpha-amino acid (1S,3R)-ACPD has been achieved using an alkylidene carbene 1,5-CH insertion reaction as a key step. The ketone cyclization precursor was synthesized from Garner's aldehyde in high yield via a Wittig homologation and subsequent catalytic hydrogenation. Treatment of the ketone with 1.2 equiv of lithio(trimethylsilyl)diazomethane in THF resulted in the formation of the corresponding cyclopentene-containing CH-insertion product in 62-69% yield in high enantiomeric excess. Subsequent functional group manipulation allowed the synthesis of the amino acid (1S,3R)-ACPD to be completed.",10.1021/jo025892v,2002-10-05,0.6287641571247001
Angewandte Chemie International Edition,Iron‐Catalyzed Synthesis of the Hexahydrocyclopenta[<i>c</i>]furan Core and Concise Total Synthesis of Polyflavanostilbene B,"The first synthesis of polyflavanostilbene B (1), which has seven contiguous stereocenters including two quaternary carbon centers, from abundant polymeric (-)-epicatechin gallate on a gram scale in three steps without the use of protecting groups is reported. The key transformations of this strategy include a regioselective and stereoselective substitution of resveratrol to give the 4-derivative of (-)-epicatechin 3-gallate and an iron-catalyzed cyclization reaction. The possible radical cyclization mechanism in the formation of the hexahydrocyclopenta[c]furan core is also discussed.",10.1002/anie.201804329,2018-07-02,0.628762992209924
Journal of Organic Chemistry,Total Synthesis of Waltherione Alkaloids: A Strategic Molecular Diversity Approach,"We report the first total synthesis of rac -8-deoxoantidesmone and rac -waltherione M, key intermediates in the unexplored 5,6,7,8-tetrahydro-1H-quinolin-4-one waltherione (THQW) alkaloid family. These compounds have been synthesized in three steps via a diversity-oriented approach utilizing a versatile intermediate 8-bromo-5-fluoro-3-methoxy-2-methyl-1H-quinolin-4-one, which was obtained through a one-step synthesis between 2-bromo-5-fluoro-aniline and ethyl 2-methoxy-3-oxo-butanoate. This intermediate underwent a MgCl 2 -mediated S N Ar reaction using alkyl Grignard reagents to provide 8-bromo-3-methoxy-2-methyl-5-alkyl-1H-quinolin-4-one. Furthermore, leveraging these common intermediates, we achieved the first total syntheses of waltherione R, 8-demethoxywaltherione F, 8-demethoxywaltherione R, walindicaone C, and walindicaone D, as well as developing a concise three-step synthesis of waltherione F.",10.1021/acs.joc.4c03068,2025-02-05,0.62874811675985
Synthesis,The Stereoselective Synthesis of the C6-C18 Fragment of Scytophycin C Employing a Novel Synthetic Methodology,"A novel synthetic approach towards the stereoselective synthesis of the C6-C18 fragment of the biologically active anti­tumor agent scytophycin C is described. The synthesis involves Marouka­ allylation, base-catalyzed intramolecular conjugate addition, Wittig olefination, and a tandem allylation.",10.1055/s-2008-1067219,2008-08-11,0.6287480939979061
Tetrahedron,A short route to furanosesquiterpenes using a new siloxyfuran building block. The synthesis of freelingnite and dehydrolasiosperman,,10.1016/s0040-4039(00)97946-2,1990-01-01,0.6287444787957364
Journal of the American Chemical Society,Enantioselective Total Synthesis of Epothilones A and B Using Multifunctional Asymmetric Catalysis,"An enantioselective total synthesis of epothilones A ( 1 ) and B ( 2 ) using multifunctional asymmetric catalysis such as a cyanosilylation of an aldehyde, an aldol reaction of an unmodified ketone with an aldehyde, and a protonation in the conjugate addition of a thiol to an α,β-unsaturated thioester has been achieved. We divided 1 and 2 into fragment A, fragment B, and fragment C. A catalytic asymmetric synthesis of fragments A and B was accomplished using a catalytic asymmetric cyanosilylation as a key step. An enantiocontrolled synthesis of fragment C was achieved in two ways. One is the use of a direct catalytic asymmetric aldol reaction of an unmodified ketone with an aldehyde as a key step, and the other utilizes a catalytic asymmetric protonation in the conjugate addition of a thiol to an α,β-unsaturated thioester as a key step. Suzuki cross-coupling of fragment A with fragment C followed by Yamaguchi lactonization as key steps led to an enantiocontrolled synthesis of epothilone A ( 1 ). On the other hand, Suzuki cross-coupling of fragment B with fragment C followed by Yamaguchi lactonization accomplished an enantiocontrolled synthesis of epothilone B ( 2 ).",10.1021/ja002024b,2000-10-18,0.6287370391448608
Journal of Organic Chemistry,Stereocontrolled Synthesis of the PPAR-γ Agonist 10-Nitrolinoleic Acid,"The naturally occurring PPAR-gamma ligand 10-nitrooctadeca-9(E),12(Z)-dienoic acid (10-nitrolinoleic acid) (2a) was prepared as a single regio- and geometrical isomer in a practical eight-step, convergent sequence. The synthetic route featured a nitro aldol reaction between 9-oxononanoic acid methyl ester (3) and 1-nitronon-3(Z)-ene (4) in the key carbon-carbon bond forming step. The ability of 2a (and its methyl ester 9) to bind to PPAR-gamma in a ligand-binding assay is reported.",10.1021/jo1007493,2010-07-01,0.6287289305368373
Journal of Organic Chemistry,"Synthesis of C<sub>11</sub>N<sub>5</sub> Marine Sponge Alkaloids:  (±)-Hymenin, Stevensine, Hymenialdisine, and Debromohymenialdisine","The synthesis of C(11)N(5) marine sponge alkaloids (+/-)-hymenin (1), stevensine (2), hymenialdisine (3), and debromohymenialdisine (4) is described. These natural products are the primary family members of the sponge metabolites that contain a fused pyrrolo[2,3-c]azepin-8-one ring system with either a 2-aminoimidazole (AI) or glycocyamidine appendage. The key steps in the synthesis centered around the generation of novel azafulvenium ions and their regioselective heterodimerization with AI in order to create the tricyclic core. A rarely used protodebromination/oxidation strategy was employed to selectively generate the desired alpha-bromo substitution pattern seen in hymenialdisine (3). In addition, the AI moiety was shown to be a useful precursor to the glycocyamidine unit found in 3 and 4, which suggests that AI-derived natural products may be the biogenic forerunners to glycocyamidine metabolites.",10.1021/jo9619746,1997-02-01,0.6287278556728618
European Journal of Organic Chemistry,"Intra‐ and Intermolecular Oxa‐Pictet–Spengler Cyclization Strategy for the Enantioselective Synthesis of Deoxy Analogues of (+)‐Nanomycin A Methyl Ester, (+)‐Eleutherin, (+)‐Allo‐Eleutherin, and (+)‐Thysanone","Abstract Enantioselective synthesis of deoxy analogues of pyranonaphthoquinone antibiotics (+)‐nanomycin A methyl ester, (+)‐eleutherin, (+)‐allo‐eleutherin, and (+)‐thysanone was achieved in good overall yield with high enantio‐ and diastereoselectivity from the common intermediate ( R )‐3‐(2,5‐dimethoxyphenyl)propane‐1,2‐diol. The intramolecular oxa‐Pictet–Spengler cyclization of 6‐aryl‐1,3‐dioxolone was developed for the first time and utilized in the enantioselective synthesis of (+)‐deoxynanomycin A methyl ester, whereas the intermolecular oxa‐Pictet–Spengler cyclization strategy was applied to the enantioselective synthesis of deoxy analogues of (+)‐eleutherin, (+)‐allo‐eleutherin, and (+)‐thysanone.",10.1002/ejoc.201000476,2010-06-23,0.6287208631852949
Journal of Organic Chemistry,"Synthesis of 2,4-Methanoproline Analogues via an Addition−Intramolecular Substitution Sequence","A new two-step synthetic approach toward 3-(chloromethyl)cyclobutanone is described and used in the synthesis of 2,4-methanoproline analogues. The key step consists of a reversible addition of hydrogen cyanide onto the imines 12 in 50-74% yield under conditions that allow ring closure. 2-Alkyl-2-azabicyclo[2.1.1]hexane-1-carbonitriles 19, synthesized in four steps, can also be converted to the corresponding amines.",10.1021/jo025897s,2002-08-15,0.6287077859077866
Synlett,A Highly Stereoselective Formal Synthesis of Hapalosin,"A flexible and highly diastereoselective formal synthesis of hapalosin, a cyclodepsipeptide isolated from the blue green alga Hapalosiphon welwitschii and having multidrug-resistance-reversing activity is described. The synthetic route involves the addition of organometallic reagent to N - tert -butanesulfinylimine, Jung nonaldol aldol reaction, and Yamaguchi esterification as key steps.",10.1055/s-0033-1338952,2013-06-05,0.628696190535021
Organic Letters,Application of Ni/Zr-Mediated Ketone Coupling for the Scalable Synthesis of Homohalichondrin B,"A practical and improved synthetic route for the scalable synthesis of homohalichondrin B has been developed. Formation of the highly stereoselective [6,6]-spiroskeleton system through a convergent Ni/Zr-mediated ketone coupling, followed by acid-promoted spiroketalization, simplified the route considerably. Higher coupling efficiency was achieved by fine-tuning the Ni I /Ni II (1:50) catalyst loadings with an equimolar (1:1) mixture of coupling partners.",10.1021/acs.orglett.4c02297,2024-08-19,0.6286794533818063
Journal of the American Chemical Society,Total Synthesis of (+)-Korupensamine B via an Atropselective Intermolecular Biaryl Coupling,The asymmetric total synthesis of nonracemic korupensamine B is reported. It includes a newly designed and highly trans-diastereoselective (>20:1 dr) route to the tetrahydroisoquinoline ring and an unprecedented atropdiastereoselective Suzuki-Miyaura coupling for construction of the fully fashioned naphthylisoquinoline framework that invokes π stacking as a possible source of stereocontrol.,10.1021/ja1065202,2010-09-17,0.6286759814450444
Synthesis,"Oxocyclopentenes, Synthesis of 2-Methoxy-4-methyl-3-oxocyclopentene and its Conversion to Dihydrojasmone","A new synthesis of dihydrojasmone starting from the disodium salt 3,5-diehthoxycarbonil-1,2-dioxocyclopentane,readly avalable by Thaoker-Bagavant procedure ,is reported.",10.1055/s-1974-23228,1974-01-01,0.6286724839438261
Organic Letters,A Highly Efficient Asymmetric Synthesis of Vernakalant,"A novel synthesis of vernakalant is described. Using inexpensive and readily available reagents, the key transformations involve (1) an efficient zinc-amine-promoted etherification, (2) a highly stereoselective enzyme-catalyzed dynamic asymmetric transamination to set up the two contiguous chiral centers in the cyclohexane ring, and (3) a pyrrolidine ring formation via alkyl-B(OH)2-catalyzed amidation and subsequent imide reduction.",10.1021/ol501002a,2014-05-01,0.628650528794115
Journal of Organic Chemistry,Cyclization Strategies for the Synthesis of Macrocyclic Bisindolylmaleimides,"Three new approaches to the synthesis of macrocyclic bisindolylmaleimides 1-4 have been identified. Two strategies afford 8, the penultimate intermediate for the synthesis of 1-4, in 73% and 32% yield by intramolecular cyclization of 31 and 40, respectively. The optimum synthesis of 1 was achieved in nine steps and 15% yield by intramolecular formation of the macrocycle and maleimide in one step by reaction of the sodium indolate of 12 with methyl indole-3-glyoxylate 47. The mechanism of this reaction has been elucidated, using the trityl-protected derivative, to involve initial formation of the tricarbonyl imide 48, followed by irreversible alkylation of the indole nitrogen to generate the 17-membered macrocycle 49. Cyclization of 49 to hydroxymaleimide 50 and subsequent dehydration afforded 8a. This approach eliminated the problem of dimerization observed in the intramolecular cyclization reactions.",10.1021/jo001605g,2001-03-01,0.6286463872816114
Organic Letters,Asymmetric Total Synthesis and Assignment of Absolute Configuration of Arbornamine,"The asymmetric total synthesis of arbornamine was accomplished in 13 steps, leading to the assignment of its absolute configuration. The key features of the strategy include construction of the C16 quaternary carbon center by a highly diastereoselective Grignard reagent addition to N - tert -butanesulfinylimine, sequential site-selective amidation and N -alkylation to form the C and E rings, and [Ni(COD) 2 ]-mediated Michael addition to close the D ring.",10.1021/acs.orglett.0c03183,2020-10-26,0.6286460008106626
Synthesis,A Facile Synthesis of (S)-4-Hydroxypyrrolidin-2-one from (S)-Malic Acid,"All articles of this category The chiral diol methyl 3,4-dihydroxybutanoate 4b obtained from ( S )-malic acid dimethyl ester ( 3b ) was subjected to regioselective tosylation to give the tosylate 6 in good yield. Subsequent treatment of 6 with aqueous ammonia afforded ( S )-4-hydroxypyrrolidin-2-one ( 1 ) through three steps in 32% overall yield from 3b . tosylation - amination - reduction - regioselective reaction",10.1055/s-1999-3460,1999-05-01,0.6286452991449153
Organic Letters,"Total Synthesis of (±)-Lysergic Acid, Lysergol, and Isolysergol by Palladium-Catalyzed Domino Cyclization of Amino Allenes Bearing a Bromoindolyl Group","Ergot alkaloids and their synthetic analogs have been reported to exhibit broad biological activity. We investigated direct construction of the C/D ring system of ergot alkaloids based on palladium-catalyzed domino cyclization of amino allenes. With this biscyclization as the key step, total synthesis of (±)-lysergic acid, (±)-lysergol, and (±)-isolysergol was achieved.",10.1021/ol200375v,2011-03-03,0.6286401134183138
Organic Letters,"Total Synthesis of (±)-Lysergic Acid, Lysergol, and Isolysergol by Palladium-Catalyzed Domino Cyclization of Amino Allenes Bearing a Bromoindolyl Group","Ergot alkaloids and their synthetic analogs have been reported to exhibit broad biological activity. We investigated direct construction of the C/D ring system of ergot alkaloids based on palladium-catalyzed domino cyclization of amino allenes. With this biscyclization as the key step, total synthesis of (+/-)-lysergic acid, (+/-)-lysergol, and (+/-)-isolysergol was achieved.",10.1021/ol8022648,2008-10-29,0.6286401134183138
Tetrahedron,A synthesis of the platelet aggregation inhibitor xemilofiban from L-aspartic acid. Confirmation of the absolute configuration,,10.1016/s0040-4039(98)00602-9,1998-05-01,0.6286394412539502
Synlett,An Enantioselective Mukaiyama Aldol Reaction as the Key Step towards the Tetrahydropyran Core of Psymberin via a γ-Butyrolactone Intermediate,"We report an alternative synthetic route towards the tetrahydropyran core of psymberin. The key steps are a catalytic enantioselective Mukaiyama aldol reaction and a syn reduction, which allowed for the rapid assembly of a γ-lactone as a precursor for the central fragment of the natural product.",10.1055/s-0031-1290379,2012-06-14,0.6286394184698857
Journal of Organic Chemistry,"Synthesis of a Trisubstituted 1,4-Diazepin-3-one-Based Dipeptidomimetic as a Novel Molecular Scaffold","We describe two routes for the synthesis of a trisubstituted 1,2,5-hexahydro-3-oxo-1H-1,4-diazepine ring (DAP), a novel, conformationally constrained, seven-membered dipeptidomimetic ring system. The linear precursor for the model DAPs, targeted for conformational analysis studies, was obtained by reductive alkylation of tert-butyl alaninate or phenylalaninate by N-Boc-alpha-amino-gamma-oxo-N,N-dimethylbutyramide. Acetylation of the newly formed secondary amine followed by acidolytic deprotection of the amino and carboxyl terminal protecting groups and subsequent diphenylphosphorazidate-mediated ring formation yielded the blocked model DAPs. The synthesis of the DAP synthon started with 1-tert-butyl hydrogen N-(benzyloxycarbonyl)aspartate. The aldehyde obtained from the beta-carboxyl was used to reductively alkylate benzyl phenylalaninate, generating a secondary amine. Hydrogenolytic deprotection of the end-groups yielded the linear precursor which was cyclized via lactam formation mediated by 1-hydroxy-7-azabenzotriazolyl-N,N,N',N'-tetramethyluronium hexafluorophosphate. This route yielded the reversibly protected hexahydro-1H-3-oxo-2(S)-benzyl-5(S)-(tert-butyloxycarbonyl)-1,4-diazepine. This synthon unit can be subsequently elaborated by substituting the functional groups (secondary amine and carboxyl). Therefore, the DAPs may serve as novel molecular scaffolds to reproduce a biologically relevant topology or as a dipeptido-conformation-mimetic that can be incorporated into bioactive peptides. In addition, these synthetic routes will allow the introduction of different chiralities at positions 2 and 5 as well as the diversification of the side chains at position 2. Furthermore, the synthetic routes described here can be easily modified to obtain larger ring systems with variable degrees of conformational flexibility.",10.1021/jo962257e,1997-04-01,0.6286365418644552
Tetrahedron,"2-Oxobenzo[h]chromene: a novel entry for the concise and efficient synthesis of indeno[1,2-c]phenanthrenes",,10.1016/j.tetlet.2007.04.087,2007-04-23,0.6286309923982988
Tetrahedron,The first total synthesis of the antitumor macrolide rhizoxin: Synthesis of the key building blocks,,10.1016/s0040-4039(00)77485-5,1993-02-01,0.6286221286133402
Tetrahedron,Synthesis of methyl acid (4-deoxy-4-guanidino-Neu5Acα2Me),,10.1016/0040-4039(95)00991-k,1995-07-01,0.6286189550321868
Tetrahedron,Synthesis of -methyl trachylobanate from levopimaric acid,,10.1016/s0040-4039(01)98772-6,1968-01-01,0.6286189550321868
Tetrahedron,"Synthesis of Methyl 5-Acetamido-3,4,5-trideoxy-4-Guanidinyl-?-glycero-?-galacto-2-nonulopyranosidonic acid (4-deoxy-4-guanidino-Neu5Acα2Me)",,10.1016/00404-0399(50)0991k-,1995-07-24,0.6286189550321868
Tetrahedron,Synthesis of the epimeric pair of 4-deoxy-4-(R)- and 4-deoxy-4-(S)-C-methyl-n-acetylneuraminic acid,,10.1016/0040-4039(90)80171-h,1990-01-01,0.6286189550321868
European Journal of Organic Chemistry,Convenient Preparation of α-Amino Acids with Bicyclopropylidene and Other Methylenecyclopropane Moieties,"Racemic bicyclopropylidenyl- (rac-11) and methylenespiropentyl- (rac-17) substituted alanines have been synthesized by iodination of bicyclopropylidenyl- and methylenespiropentylmethanols 7, 13, nucleophilic substitution of the iodine in 8, 14 with the enolate of ethyl α-(diphenylmethyleneamino)acetate (O'Donnell's glycine equivalent) and deprotection of 9, 15 in 24 and 18% overall yield, respectively. N-Methylbicyclopropylidenylalanine rac-22, was obtained from the Michael adduct of (bicyclopropylidenyl)magnesium bromide 18 to enamine 19 and deprotection of the carbamate 20 (23% overall yield). Racemic (1-amino-2-methylenespiropentane)- (37), (1-amino-2-methylenecyclopropane)- (3), and (1-aminobicyclopropylidene)carboxylic acid (39) were prepared as hydrochlorides by tert-butoxycarbonylation of the lithiated methylenespiropentane (6), methylenecyclopropane (4), or bicyclopropylidene (5) intermediates with di-tert-butyl pyrocarbonate (Boc2O), repeated lithiation of the tert-butyl esters 29, 30, and 33 with LDA and subsequent carboxylation, Curtius degradation of the half esters 31, 32, and 34 followed by deprotection in 11, 45, and 4% overall yields, respectively. Compound 37 was also prepared from bicyclopropylidene (5) following the same procedure, but with rearrangement in the last but one step, in 19% overall yield. An attempted Hofmann degradation of the bicyclopropylidenecarboxamido ester 40 with NBS failed and gave only bromohydrin 44 (27%), but with bis(acetoxy)iodobenzene provided carbamate 46a, b in 76 amd 79% yield, respectively. Along this route with subsequent deprotection of 46b, the amino acid 39 could be prepared in up to 10% overall yield from bicyclopropylidene.",10.1002/(sici)1099-0690(199812)1998:12<2785::aid-ejoc2785>3.0.co;2-r,1998-12-01,0.6286054595978646
Tetrahedron,An alternative synthetic route to compactin via a michael-alkylation sequence,,10.1016/s0040-4039(01)91286-9,1984-01-01,0.6285988080174396
Organic Letters,Total Synthesis of Ajudazol A by a Modular Oxazole Diversification Strategy,The total synthesis of the potent respiratory chain inhibitor ajudazol A was accomplished by a concise strategy in 17 steps (longest linear sequence). The modular approach was based on a direct oxazole functionalization strategy involving a halogen dance reaction for selective halogenation in combination with a challenging combination of sp 2 –sp 2 and sp 2 –sp 3 Negishi cross coupling reactions. The applicability of this strategy for analogue synthesis was demonstrated by the synthesis of a simplified as well as stabilized ajudazol analogue.,10.1021/acs.orglett.0c02188,2020-08-06,0.6285967552739677
Organic Process Research & Development,An Efficient Process for the Manufacture of Carmegliptin,"A short and high-yielding synthesis of carmegliptin ( 1 ) suitable for large-scale production is reported. The tricyclic core was assembled efficiently by a decarboxylative Mannich addition−Mannich cyclization sequence. Subsequent crystallization-induced dynamic resolution of enamine 7 using ( S, S )-dibenzoyltartaric acid was followed by diastereoselective enamine reduction to give the fully functionalized tricyclic core with its three stereogenic centers. The C-3 nitrogen was introduced by Hofmann rearrangement of amide 28, and the resulting amine 10 was coupled with ( S )-fluoromethyl lactone 31 . Following cyclization to lactam 13 and amine deprotection, 1 was obtained in 27−31% overall yield with six isolated intermediates.",10.1021/op2000207,2011-05-05,0.6285904258227573
Organic Letters,Total Synthesis of <i>ent</i>-Plagiochianin B,An enantioselective total synthesis of plagiochianin B is described that employs (+)-3-carene as its point of departure and delivers the enantiomer of the natural product. Key features of the synthesis include a palladium-mediated regioselective oxidative cleavage of an olefin residing on a pyridine derived from a 6π-azatriene electrocyclization.,10.1021/acs.orglett.0c04219,2021-01-30,0.6285702473907802
Journal of Organic Chemistry,Synthesis of 3-Selenylindoles through Organoselenium-Promoted Selenocyclization of 2-Vinylaniline,"A novel metal-free one-pot protocol for the synthesis of potential biologically active molecules 3-selenylindoles via intramolecular cyclization/selenylation with simple 2-vinylaniline has been developed with moderate to good yield, thus representing it as a facile route to diverse substitution patterns around the indole core. The reaction proceeded smoothly with a broad substrate scope and excellent functional group tolerance. Moreover, the present synthetic route could be readily scaled up to gram quantity without difficulty. Mechanistic studies have revealed that in situ formed selenium electrophile species may be the key intermediate for the selenocyclization process.",10.1021/acs.joc.0c01918,2020-11-05,0.6285625552333433
Synthesis,"A Convenient, Gram-Scale Synthesis of 1-Deoxymannojirimycin","A novel gram-scale synthesis of 1-deoxymannojirimycin from tetra- O -benzyl- d -glucopyranose in 9 steps and 28% overall yield with a limited number of purification steps is reported. The synthetic strategy is based on the regioselective deprotection and subsequent inversion of configuration of the OH group at C-2 in tetra- O -benzyl- d -glucono-δ-lactam, also an advanced intermediate toward the synthesis of 1-deoxynojirimycin derivatives.",10.1055/s-0035-1561323,2016-01-20,0.6285617139746017
Journal of the American Chemical Society,A Novel and Efficient Synthesis of a Highly Active Analogue of <i>clasto</i>-Lactacystin β-Lactone,"Herein, we describe a new convergent synthesis of a more potent analogue of clasto -lactacystin β-lactone ( 2 ), PS-519 compound 4, which is currently in preclinical development for the treatment of ischemia−reperfusion injury in stroke and myocardial infarction. The synthetic strategy relies on building two intermediates (an oxazoline and an aldehyde) which are joined through a doubly diastereoselective aldol reaction, setting up the requisite unichiral centers in the final product ( 4 ). The facial selectivity and ultimate stereocontrol are achieved by employing a trivalent aluminum Lewis acid, Me 2 AlCl, in a chelation-induced reaction which yields a single aldol adduct. The efficiency of the synthetic approach has allowed for the preparation of multigram quantities of clinical grade material, which will support Phase I studies.",10.1021/ja991175f,1999-10-13,0.6285496963422692
Tetrahedron,Development of synthetic routes to macrocyclic compounds based on the HSP90 inhibitor radicicol,,10.1016/j.tetlet.2006.01.116,2006-02-11,0.6285245723531322
European Journal of Organic Chemistry,Enantiospecific Total Synthesis of (−)‐Hyacinthacine A<sub>1</sub> and (+)‐Hyacinthacine A<sub>1</sub> and Their Homologues Using Nitrogen Substituted Donor–Acceptor Cyclopropane,"Abstract A concise and efficient enantiospecific total synthesis of (−)‐hyacinthacine A 1 and (+)‐hyacinthacine A 1 was achieved from commercially available starting material L‐pyroglutamic acid and D‐glutamic acid, respectively. For the synthesis of this trihydroxylated pyrrolizidine ring, we employed the nitrogen‐substituted donor‐acceptor cyclopropane as a key intermediate. The synthetic approach relies on two crucial steps, highly stereo‐ and regioselective intramolecular cyclopropanation with Rh 2 (OAc) 4 and regioselective ring opening of a nitrogen‐substituted donor‐acceptor cyclopropane.",10.1002/ejoc.202300818,2023-09-11,0.6285224115489098
Tetrahedron,"An efficient, enantioselective synthesis of branched polyhydroxylated pyrrolidines",,10.1016/s0040-4039(00)01452-0,2000-12-01,0.6284756493346887
Journal of Organic Chemistry,An Efficient RCM-Based Synthesis of Orthogonally Protected<i>m</i><i>eso</i>-DAP and FK565,"A condensation--ring-close--ring-open sequence was employed for the synthesis of orthogonally protected meso-2,6-diaminopimelic acid, starting from easily accessible chiral synthons. Condensation of suitably protected L-allylglycine and D-vinylglycinol derivatives was followed by Grubbs' ring-closing metathesis to generate the key lactam intermediate. This strategy has been applied to a concise total synthesis of the potent immunostimulatory peptide FK565.",10.1021/jo0485738,2004-11-09,0.6284719600227869
Synthesis,Total Synthesis of (±)-Cephalosol via Silyl Enol Ether Acylation,An efficient total synthesis of (±)-cephalosol is reported. Key steps are the acylation of a silyl enol ether with monomethyl oxalyl chloride and the subsequent acid-mediated ring closure to the isocoumarin structure. A chemoselective allylation and the conversion of the olefin into a methyl acetate were applied to install the γ-lactone moiety.,10.1055/s-0029-1218647,2010-01-12,0.6284691541797012
Synlett,A Review of Advances in the Synthesis of Analogues of the <i>Delphinium</i> Alkaloid Methyllycaconitine,"Neuronal nicotinic acetylcholine receptors of the a7 subtype are potential targets for drug development in the treatment of Alzheimer’s disease. The Delphinium alkaloid methyllycaconitine is a potent and selective a7 sub-type selective nicotinic acetylcholine receptor antagonist. The total synthesis of this pharmacologically active alkaloid has not yet been achieved. A summary of semisynthetic methods to prepare methyllycaconitine is presented. Existing synthetic strategies used to prepare E, AE, AEF, ABE, ABDE, ABEF ring analogues of methyllycaconitine are reviewed for the first time.",10.1055/s-2005-871575,2005-06-22,0.6284612239462352
Journal of the American Chemical Society,Concise Synthesis and Antimicrobial Evaluation of the Guanidinium Alkaloid Batzelladine D: Development of a Stereodivergent Strategy,"), and a series of stereochemical analogues and explore their antimicrobial activity for the first time. The concise synthetic approach enables access to the natural products in a sequence of 8-12 steps from readily available building blocks. Highlights of the synthetic strategy include gram-scale preparation of a late stage intermediate, pinpoint stereocontrol around the tricyclic skeleton, and a modular strategy that enables analogue generation. A key bicyclic β-lactam intermediate not only serves as the key controlling element for pyrrolidine stereochemistry but also serves as a preactivated coupling partner to install the ester side chain. The stereocontrolled synthesis allowed for the investigation of the antimicrobial activity of batzelladine D, demonstrating promising activity that is more potent for non-natural stereoisomers.",10.1021/jacs.0c04091,2020-05-12,0.6284608246092533
Organic Letters,Total Synthesis of (−)-Lepadiformine A Utilizing Hg(OTf)<sub>2</sub>-Catalyzed Cycloisomerization Reaction,"A cytotoxic marine alkaloid (-)-lepadiformine A (1) possesses a unique structure characterized by the trans-1-azadecalin AB ring system fused with the AC spiro-cyclic ring. In this research, we found that a cycloisomerization reaction from amino ynone 2 to a 1-azaspiro[4.5]decane skeleton 3, corresponding to the AC ring system of 1, is promoted by Hg(OTf)(2). Thus, we have accomplished the efficient total synthesis of (-)-lepadiformine A in 28% overall yield by featuring the novel Hg(OTf)(2)-catalyzed cycloisomerization.",10.1021/acs.orglett.5b02867,2015-11-19,0.6284592864227581
Tetrahedron,Total synthesis of the natural isoprenylcysteine carboxyl methyltransferase inhibitor spermatinamine,,10.1016/j.tetlet.2009.06.087,2009-06-22,0.6284410903463632
Synthesis,Synthesis of 2′-Deoxy-2′-<b> <i>C</i> </b>-α-methylpurine Nucleosides,"2′-Deoxy-2′-C-α-methylribonucleosides provide valuable biochemical probes with which to study RNA structure and function. Using methyl 2-acetoxymethyl-3,5-di-O-(tert-butyldi­methylsilyl)-d-ribofuranoside (1) as a glycosylating agent, we achieved in four steps an improved synthesis of 2′-deoxy-2′-C-α-methyladenosine (8) and the first synthesis of 2′-deoxy-C-α-methylguanosine (9) in 25% and 17% overall yield, respectively.",10.1055/s-2005-872204,2005-01-01,0.6284223496466202
Synlett,An Efficient Enantioselective Total Synthesis of Atorvastatin Calcium,"Abstract A concise and efficient asymmetric synthesis of tert-butyl [(4R,6R)-6-(2-aminoethyl)-2,2-dimethyl-1,3-dioxan-4-yl]acetate is presented. This key chiral-chain precursor of atorvastatin was synthesized from a commercially available inexpensive starting material, and was converted into atorvastatin calcium. The synthesis has the potential for scale up, and could be used to produce atorvastatin calcium on an industrial scale.",10.1055/a-1970-8386,2022-11-02,0.6284058774955619
Journal of Organic Chemistry,"Evolution of a Short and Stereocontrolled Synthesis of (+)-7,20-Diisocyanoadociane","A full account of the development of a concise and highly stereoselective synthesis of (+)-7,20-diisocyanoadociane (DICA)─a structurally complex isocyanoditerpene with potent antiplasmodial activity─is described. The strategy that evolved relies on the rapid construction of unsaturated tricyclic precursors designed to undergo stereocontrolled Birch reductions and a subsequent ""bay ring"" formation to generate the isocycloamphilectane core. This report is divided into three sections: (1) a description of the initial strategy and the results that focused our efforts on a single route to the DICA core, (2) a discussion of the precise choreography needed to enable a first-generation formal synthesis of (±)-DICA, and (3) the execution of a 13-step second-generation synthesis of (+)-DICA that builds on important lessons learned from the first-generation effort.",10.1021/acs.joc.1c02700,2022-01-06,0.6283994134590399
Organic Letters,"Asymmetric Hydrogenation of Exocyclic α,β-Unsaturated Nitriles: An Access to Chiral 2-Benzocyclic Acetonitriles and Ramelteon","A highly efficient and enantioselective hydrogenation of exocyclic α,β-unsaturated nitriles catalyzed by the Rh-JosiPhos complex for synthesis of the chiral 2-benzocyclic acetonitriles has been developed. Both ( Z )- and ( E )-isomers of exocyclic α,β-unsaturated nitriles with various benzocyclic structures, including heterocyclic (chroman and tetrahydroquinoline) scaffolds, were hydrogenated successfully, achieving excellent enantioselectivities (up to 97% ee) and high turnover numbers (TON up to 4000). Furthermore, this methodology provides an efficient, concise, and practical synthetic route to the sleep agent ( S )-Ramelteon.",10.1021/acs.orglett.4c03693,2024-12-09,0.6283962846678239
Organic Process Research & Development,"Development of a Multigram Preparation of Optically Pure (−)-7-(Bromomethylene)-3-amidobicyclo[2.2.1]heptane-2-carboxamide BMT-395137, a Versatile Scaffold for Divergent Drug Discovery Synthesis","This paper describes the development of a synthetic route for the multigram synthesis of (−)-(1 R,2 S,3 R,4 R, Z )-7-(bromomethylene)- N -(4-fluoro-3-(trifluoromethyl)phenyl)-3-(2,2,2-trifluoroacetamido)bicyclo[2.2.1]heptane-2-carboxamide ((−) -14, BMT-395173), a versatile scaffold for divergent drug discovery synthesis. This new process begins with readily available commercial starting materials and includes a highly scalable stereoselective Diels–Alder reaction between ( Z )-4-(benzyloxy)-4-oxobut-2-enoic acid ( 21 ) and ferrocenium hexafluorophosphate ( 15 ), resulting in the formation of alcohol rac-20 . Additionally, a stereoselective Wittig reaction of ketone rac-10 with (bromomethyl)triphenylphosphonium bromide introduces the bromomethylene group of (−) -14 . The process was applied to the preparation of over 100 g of optically pure BMS-395173 via multiple batches for preclinical chemotype optimization.",10.1021/acs.oprd.5c00208,2025-08-07,0.62839235581529
Journal of the American Chemical Society,Total Synthesis of (±)-Rubriflordilactone A,A new and efficient synthesis of rubriflordilactone A has been realized. The key transformations include the following: (1) an intramolecular Prins cyclization to establish the seven-membered ring containing two contiguous stereocenters; (2) a Mukaiyama hydration/oxa-Michael cascade to construct the B-ring; and (3) an unprecedented stereocontrol intermolecular o -QM type [4 + 2]-cycloaddition to rapidly assemble core structure of rubriflordilactone A.,10.1021/jacs.4c01033,2024-03-08,0.6283901007600632
Organic Letters,Total Synthesis of (+)-Discodermolide:  A Highly Convergent Fourth-Generation Approach,"[structure: see text] A highly convergent, fourth-generation total synthesis of (+)-discodermolide (1), with a longest linear sequence of 17 steps and an overall yield of 9.0%, has been achieved. Highlighting the strategy is the efficient construction and sequential, bidirectional union of a linchpin comprising the C(9)-C(14) Wittig salt-vinyl iodide (-)-18. Importantly, Wittig salt generation proceeded in excellent yield under ambient pressure.",10.1021/ol050455z,2005-03-31,0.6283870499157045
Journal of Organic Chemistry,Synthesis of the ABC Core of <i>Daphniphyllum</i> Alkaloids with a [5–6–7] Azatricyclic Scaffold via Ring Expansion of Azabicyclic and Azatricyclic Building Blocks,"High Resolution Image Download MS PowerPoint Slide The [5–6–7] azatricyclic ABC core, found in several Daphniphyllum alkaloids, has been synthesized through a novel route involving ring expansion of a perhydroindolone to afford the AC ring system and a radical B ring closure as key steps. The level of functionalization of the reported octahydro-1,7-ethanocyclohepta[ b ]pyrroles suggests that they can serve as valuable building blocks in this alkaloid field. Also reported is the first synthesis of homomorphans by the ring enlargement of 2-azabicyclo[3.3.1]nonanes.",10.1021/acs.joc.4c01090,2024-07-01,0.6283837850380992
Synlett,"2,3-Dihydro-4H-1,3-oxazin-4-ones, Novel Auxiliaries for the Stereoselective Synthesis of 1β-methylcarbapenems","All articles of this category Dihydrooxazinones 9 , prepared from benzylcyanide in two steps serve as efficient auxiliaries for the stereoselective synthesis of β-methylcarbapenem intermediate 2 . Reformatsky-type reactions of 4-acetoxyazetidinone with α-bromopropionyl dihydrooxazinone 10 provided β-methylazetidinones 4 in high diastereoselectivities. The auxiliaries 9 were also easily removed in the Dieckmann cyclization leading to β-methylcarbapenem skeletons. Practical synthesis of β-methylenolphosphates 2 from 4-acetoxyazetidinone 3 was achieved in three steps (61-77% overall yield). auxiliary - diastereoselective - β-methylcarbapenem - Reformatsky-type reaction - Dieckmann cyclization",10.1055/s-2001-18778,2001-01-01,0.628381279875782
Journal of the American Chemical Society,"Fully Stereocontrolled Total Syntheses of the Prostacyclin Analogues 16<i>S</i>-Iloprost and 16<i>S</i>-3-Oxa-Iloprost by a Common Route, Using Alkenylcopper-Azoalkene Conjugate Addition, Asymmetric Olefination, and Allylic Alkylation","In this article we describe fully stereocontrolled total syntheses of 16S-iloprost (16S-2), the most active component of the drugs Ilomedin and Ventavis, and of 16S-3-oxa-iloprost (16S-3), a close analogue of 16S-2 having the potential for a high oral activity, by a new and common route. The key steps of this route are (1) the establishment of the complete C13-C20 omega side chain of the target molecules through a stereoselective conjugate addition of the alkenylcopper derivative 9 to the bicyclic C6-C12 azoalkene 10 with formation of hydrazone 8, (2) the diastereoselective olefination of ketone 7 with the chiral phosphoryl acetate 39, and (3) the regio- and stereoselective alkylation of the allylic acetate 43 with cuprate 42. These measures allowed the 5E,15S,16S-stereoselective synthesis of 16S-2 and 16S-3, a goal which had previously not been achieved. Azoalkene 10 was obtained from the achiral bicyclic C6-C12 ketone 11 as previously described by using as key step an enantioselective deprotonation. The configuration at C16 of omega-side chain building block 9 has been installed with high stereoselectivity by the oxazolidinone method and that at C15 by a diastereoselective oxazaborolidine-catalyzed reduction of the C13-C20 ketone 23 with catecholborane. Surprisingly, a high diastereoselectivity in the reduction of 23 was only obtained by using 2 equiv of oxazaborolidine 24. Application of substoichiometric amounts of 24 resulted in irreproducible diastereoselectivities ranging from very high to nil.",10.1021/ja0558037,2005-11-25,0.6283785724068135
Journal of Organic Chemistry,"Synthesis of Ring-Fused, N-Substituted 4-Quinolinones Using p<i>K</i><sub>a</sub>-Guided, Base-Promoted Annulations with Isatoic Anhydrides: Total Synthesis of Penicinotam","An anionic annulation strategy employing isatoic anhydrides and a wide assortment of enolizable partners was developed to afford over 80 novel ring-fused, N-substituted 4-quinolinones, an underrepresented privileged template. Multiple factors governing the efficiency of the transformation were determined, resulting in a reliable and tunable synthetic platform applicable for a broad range of substrates with variable deprotonation susceptibility, such as tetramic and tetronic acids, cyclic 1,3-diketones, and cycloalkanones. Application to the synthesis of bioactive, pyrrolizine-fused 4-quinolinone, penicinotam 3, resulted in the most brief and highest yielding total synthesis of the alkaloid in three steps and a 36% overall yield.",10.1021/acs.joc.9b02541,2019-12-02,0.628358239816478
Journal of Organic Chemistry,Ellagitannin Chemistry. Syntheses of Tellimagrandin II and a Dehydrodigalloyl Ether-Containing Dimeric Gallotannin Analogue of Coriariin A,"The first chemical synthesis of the naturally occurring ellagitannin tellimagrandin II is reported. Key steps of the synthesis include the atropselective oxidative coupling of suitably protected galloyl rings at the O(4) and O(6) positions of a glucopyranose core, and the stereoselective acylation of the derived anomeric alcohol with a galloyl chloride. In addition, the synthesis of a novel gallotannin-ellagitannin hybrid is described. This dimeric construct relied on a hetero Diels-Alder cycloaddition/reductive rearrangement sequence to deliver the intact skeleton from a monomeric pentagalloylglucose-based orthoquinone.",10.1021/jo9816966,1998-12-09,0.6283547426370427
Chemical Science,Asymmetric total synthesis of penicilfuranone A through an NHC-catalyzed umpolung strategy,"The first asymmetric total synthesis of penicifuranone A was accomplished in eight steps through an NHC-catalyzed umpolung strategy. Key features of the synthesis include an Al-Salen catalyzed asymmetric cyanosilylation to install the tertiary alcohol of gregatin A, and an NHC catalyzed Stetter-Aldol cascade reaction. The umpolung strategy of the benzyl aldehyde fragment facilitated a convergent formal [4 + 2] annulation with gregatin A, ultimately leading to the formation of penicifuranone A.",10.1039/d5sc01508a,2025-01-01,0.6283354214615626
Journal of Organic Chemistry,Total Synthesis of (−)-Sacidumlignans B and D,"The first total synthesis of naturally occurring sacidumlignans A (1), B (2), and D (4) was executed and the absolute configuration of 2 and 4 was determined. A diastereoselective α- methylation of a lactone was used as the key step for the control of the chiral centers of the central lignan core. An acid mediated dehydrative cyclization of an aldehyde to construct the dihydronaphthalene unit of 2 and the aromatization of the intermediate dihydronaphthalene derivative to synthesize 1 are the key reactions employed in this regard.",10.1021/jo2021696,2012-01-04,0.6283276939041943
Tetrahedron,"Towards the total synthesis of the anti-trypanosomal macrolide, Actinoallolides: construction of a key linear intermediate",,10.1016/j.tetlet.2015.12.022,2015-12-12,0.6283126930923819
Tetrahedron,Applications of chiral allenylzinc additions and Noyori asymmetric reductions to an enantioselective synthesis of a C3–C13 precursor of the polyketide phosphatase inhibitor cytostatin,,10.1016/j.tetlet.2003.12.067,2004-01-16,0.6283102176617855
Organic Letters,Total Synthesis of (+)-Dixiamycin C via a Late-Stage Ni(II)-Photoredox <i>N</i>-Arylation of Carbazoles,"We report the asymmetric total synthesis of dixiamycin C (1) through the shrewd alliance of the naturally occurring monomer xiamycin A methyl ester (5) and its bromo derivative (31) following a late-stage Buchwald–Macmillan’s C–N bond formation via a photoredox electron transfer approach with a less reactive carbazole nitrogen. The key step in the synthesis of monomer xiamycin A methyl ester (5) involves Buchwald’s Pd(II)-mediated aerobic dehydrogenative C–N bond formation, Beckmann rearrangement, and ipso -acetylation of an electron-rich aromatic ring of an abietane core.",10.1021/acs.orglett.4c02436,2024-08-21,0.6283039210887672
Tetrahedron,Scalable syntheses of the BET bromodomain inhibitor JQ1,"We have developed methods involving the use of alternate, safer reagents for the scalable syntheses of the potent BET bromodomain inhibitor JQ1. A one-pot three step method, involving the conversion of a benzodiazepine to a thioamde using Lawesson's reagent, followed by amidrazone formation and installation of the triazole moiety furnished JQ1. This method provides good yields and a facile purification process. For the synthesis of enantiomerically enriched (+)-JQ1, the highly toxic reagent diethyl chlorophosphate, used in a previous synthesis, was replaced with the safer reagent diphenyl chlorophosphate in the three-step one-pot triazole formation without effecting yields and enantiomeric purity of (+)-JQ1.",10.1016/j.tetlet.2015.02.062,2015-05-23,0.6283000807152536
Journal of the American Chemical Society,A Concise Synthesis of the Octalactins,"The total synthesis of octalactins A and B has been achieved in 15 steps (longest linear sequence) and 10% overall yield from commercially available materials. Key steps include the Paterson-Aldol reaction for the rapid assembly of the carbonate 46, methylenation of 46 and subsequent Claisen rearrangement of the corresponding alkenyl-substituted cyclic ketene acetal to provide the core unsaturated medium-ring lactone 47, and the use of enzyme-mediated acetate deprotection in the presence of a medium-ring lactone.",10.1021/ja038353w,2004-02-01,0.6282833270108569
Journal of Organic Chemistry,A Concise Synthesis of (±)-Cacalol,"A simple synthesis of the natural product cacalol has been developed that proceeds in seven steps and 21-25% overall yield. Ortho-lithiation of 4-methylanisole and alkylation with 5-iodo-1-pentene, followed by intramolecular Friedel-Crafts alkylation, gave 5-methoxy-1,8-dimethyltetralin. This compound was then formylated in the 6-position. Baeyer-Villiger oxidation and hydrolysis of the resulting formate gave 6-hydroxy-5-methoxy-1,8-dimethyltetralin. Alkylation of the phenolic hydroxyl group with chloroacetone followed by cyclodehydration gave cacalol methyl ether. Deprotection of this aryl methyl ether yielded cacalol.",10.1021/jo800324c,2008-05-29,0.6282317840152318
Journal of Organic Chemistry,Enantioselective Total Synthesis of the Antitumor Macrolide Rhizoxin D,"The convergent, highly enantioselective synthesis of rhizoxin D, a natural product possessing potent antitumor and antifungal bioactivity, is described. The C(1)-C(9) fragment of the molecule was synthesized utilizing a threefold pseudosymmetric intermediate ultimately derived from gamma-butyrolactone. The central core of rhizoxin D was prepared via a chiral resolution/asymmetric aldol protocol. Several methods for the generation of the polyene fragment were explored, and the side-chain was ultimately prepared from serine in six steps. The unification of the left and right wings of the molecule was achieved using a one-step olefination protocol, and the macrocyclization was carried out using a Horner-Emmons olefination at the C(2)-C(3) olefin.",10.1021/jo034011x,2003-04-19,0.6282141752107361
Journal of the American Chemical Society,Total Synthesis of Cribrostatin IV:  Fine-Tuning the Character of an Amide Bond by Remote Control,"We report the enantioselective total synthesis of cribrostatin IV (1). Key features of this synthesis involve the convergent coupling of two highly functionalized homochiral components followed by a ""lynchpin"" Mannich cyclization to establish the pentacyclic core (cf. 19 --> 20).",10.1021/ja050203t,2005-03-10,0.628212195376526
Tetrahedron,Synthesis of (±)-CP-99994: A highly potent substance P antagonist,,10.1016/s0040-4039(00)73791-9,1993-09-01,0.6282001421148067
Synlett,"A Highly Efficient Synthesis Route for the Rapid Generation of 1,2,5,6-Tetrasubstituted Benzimidazoles",Herein we describe the facile generation of novel benzimidazoles starting from 5-chloro-4-iodo-2-nitroaniline. A synthesis protocol was established which allows the parallel synthesis of compound arrays as well as the rapid generation of single representatives thereof.,10.1055/s-2008-1077791,2008-06-01,0.6281921258565086
Tetrahedron,gem-cyclodialkylation A facile synthetic route to N-substituted heterocycles,,10.1016/s0040-4039(00)89006-1,1990-01-01,0.6281796479231208
Journal of the American Chemical Society,Three-Fold Scholl-Type Cycloheptatriene Ring Formation around a Tribenzotriquinacene Core: Toward Warped Graphenes,"A nonplanar polycyclic aromatic compound 6 bearing a tribenzotriquinacene (TBTQ) core merged with an o,p,o,p,o,p-hexaphenylene belt was prepared and characterized by NMR spectroscopy and X-ray crystallography. The key synthesis step involves three Scholl-type cycloheptatriene ring formation steps of the 1,4,8-tris(3',4'-dimethoxyphenyl)-TBTQ derivative 5. The bridging of each of the three TBTQ bays by 1,2-phenylene units in compound 6 gives rise to an unusual wizard hat shaped structure, which represents a promising key intermediate for the construction of nonplanar nanographene molecules bearing a TBTQ core.",10.1021/jacs.6b05820,2016-08-01,0.6281723552197791
Journal of Organic Chemistry,Asymmetric Total Synthesis of (−)-Pavidolide B via a Thiyl-Radical-Mediated [3 + 2] Annulation Reaction,"The development of an efficient strategy for the asymmetric total synthesis of the bioactive marine natural product (-)-pavidolide B is described in detail. The development process and detours leading to the key thiyl-radical-mediated [3 + 2] annulation reaction, which constructed the central C ring with four contiguous stereogenic centers in one step, are depicted. Subsequently, the seven-membered D ring is constructed via a ring-closing metathesis reaction followed by a Rh(III)-catalyzed isomerization. This strategy enables the total synthesis of (-)-pavidolide B in the longest linear sequence of 10 steps.",10.1021/acs.joc.9b02230,2019-11-21,0.6281705589470636
Angewandte Chemie International Edition,A Convergent and Stereoselective Synthesis of the Glycolipid Components Phthioceranic Acid and Hydroxyphthioceranic Acid,"Simply convergent: The polydeoxypropionates 1 and 2 are important constituents of the cell wall of Mycobacterium tuberculosis. Key steps in their total synthesis include two Suzuki–Miyaura cross-coupling reactions and two highly diastereoselective iridium-catalyzed hydrogenations. The trideoxypropionates employed as central building blocks were prepared by sequential oxy-Cope rearrangement, hydrogenation, and enolate methylation.",10.1002/anie.201303776,2013-07-10,0.6281603788003073
Organic Letters,Improved Synthesis of the ABCDE Fragment of Brevetoxin A,"A second-generation synthesis of the BCDE fragment of brevetoxin A is described. Novel reactions were developed that extend the utility of the asymmetric glycolate alkylation reaction and improve scale-up to provide gram quantities of the B and E subunits. Significant improvements to the convergent assembly of the tetracycle were also realized. In addition, formation of the A ring lactone was accomplished to complete the ABCDE pentacycle.",10.1021/ol0615782,2006-08-01,0.6281484555053194
Organic Process Research & Development,Industry-Oriented Route Evaluation and Process Optimization for the Preparation of Brexpiprazole,"Efforts toward route evaluation and process optimization for the preparation of brexpiprazole ( 1 ) are described. Starting from commercially available dihydroquinolinone 11, a three-step synthesis route composed of O -alkylation, oxidation, and N -alkylation was selected for industry-oriented process development aiming to reduce side reactions and achieve better impurity profiles. The reaction conditions of the three steps were investigated, and the control strategy for the process-related impurities was established. The optimized process was validated on the kilogram scale and now is viable for commercialization, with the results of not less than 99.90% purity of 1 (by HPLC) and not more than 0.05% of persistent impurities 15 and 16 .",10.1021/acs.oprd.8b00438,2019-03-08,0.6281462940938521
Synlett,"Synthesis of Indolo[2,1-<i>a</i>][2]benzazepineand Indolo[2,1-<i>a</i>][2]-benzazocine","The synthesis of functionalised 6,7-dihydro-5H-indolo[2,1-a][2]benzazepine and 5,6,7,8-tetrahydroindolo[2,1-a][2]benz­azocine from methyl 2-bromo-3-cyclohexyl-1H-indole-6-carboxy­late, involving RCM as the key step to generate the tetracyclic indolo[2,1-a][2]benzazepine and indolo[2,1-a][2]benzazocine core structure, is outlined.",10.1055/s-0029-1217168,2009-05-13,0.6281388451883653
Synlett,Synthetic Development of Radicicol and Cycloproparadicicol: Highly Promising Anticancer Agents Targeting Hsp90,"Molecular chaperone Hsp90 has emerged as one of the most exciting new targets for anticancer therapy. Natural product-based modulators, such as radicicol (1), inhibit Hsp90 and induce the breakdown of its client proteins, thereby blocking multiple critical oncogenic pathways. Several total synthesis endeavors directed toward radicicol have been accomplished. Cycloproparadicicol (2), a potent Hsp90 inhibitor and highly promising pre-clinical anticancer agent, was discovered through a convergent total synthesis approach. In an effort to devise a more efficient and concise route to reach 2, a novel ‘ynolide’ protocol, featuring an ynolide-bissiloxydiene Diels-Alder addition, was designed and reduced to practice. This methodology was also extended to aigialomycin D.",10.1055/s-2004-829052,2004-01-01,0.6281307906172731
Tetrahedron,"Practical, convergent total synthesis of polyamine amide spider toxin NSTX-3",,10.1016/0040-4039(95)02238-4,1996-01-01,0.628124092367064
Journal of Organic Chemistry,"Synthesis of Pyridopyrazine-1,6-dione γ-Secretase Modulators via Selective 4-Methylimidazole <i>N</i><sup>1</sup>-Buchwald Arylation","An efficient synthesis of pyridopyrazine-1,6-dione γ-secretase modulators (GSMs) is described. Our route features the construction of a crystalline lactone intermediate via a selective palladium-catalyzed 4-methylimidazole N 1 -arylation using the Buchwald Xantphos Pd G4 precatalyst, which does not require a preactivation step. The weak inorganic base KHCO 3 was employed to minimize saponification of a particularly sensitive lactone substrate. Additional key transformations include DABAL-Me 3 -mediated lactone aminolysis and a mild TBD/ethyl trifluoroacetate mediated lactam ring closure to afford a representative GSM in high yield.",10.1021/acs.joc.8b02953,2019-01-08,0.6281222362549722
Synthesis,Stereoselective Synthesis of the C27–C35 Eribulin Fragment and Its Utilization in Building Structurally Diverse Macrocycles,"A practical and scalable stereoselective synthesis of the western substituted tetrahydrofuran ring C27–C35 fragment of eribulin was developed by using (2 S ,3 S )-tartaric acid as a cheap starting material that was converted into an intermediate through a stereoselective vinylation­ and cross-metathesis as the key steps. A regio- and stereo­selective intramolecular oxy-Michael cyclization or an iodocyclization reaction finally provided the required western tetrahydrofuran ring fragment and its related isomeric analogues. These key fragments were further utilized in obtaining several types of macrocyclic derivatives for exploration of their biological properties. The simplicity of our present approach has the potential to be considered for large-scale syntheses of key fragments of eribulin and related analogues.",10.1055/s-0035-1561431,2016-04-19,0.6281178145708649
Organic Process Research & Development,"Large-Scale Negishi Coupling as Applied to the Synthesis of PDE472, an Inhibitor of Phosphodiesterase Type 4D","5-[2-Methoxy-5-(4-pyridinyl)phenyl]-2,1,3-benzoxadiazole (PDE472) is a selective inhibitor of the phosphodiesterase PDE4D isoenzyme, which is a recognised drug target for the treatment of asthma. Different synthetic routes to PDE472 were investigated, and the research synthesis was optimised to prepare a phase I batch on pilot-plant scale with the focus on the elimination or minimization of inherent process risks. An important refinement of the key Negishi aryl−aryl coupling involved preforming the arylpalladium complex, which was then added to the arylzinc intermediate. Residual palladium was removed from PDE472 via crystallization of the hemi-maleate salt, which afforded drug-substance containing <2 ppm Pd.",10.1021/op025615q,2003-04-04,0.6281068137820653
Tetrahedron,"The synthesis and stability of aziridino-glutamate, an irreversible inhibitor of glutamate racemase",,10.1016/s0040-4039(00)73115-7,1994-06-01,0.6280784964212008
Organic Letters,Efficient Synthesis of 5-Hydroxymethylcytosine Containing DNA,"5-Hydroxymethylcytosine ((5-HOMe)dC) was recently discovered as the sixth base in the mammalian genome. The development of a new phosphoramidite building block is reported, which allows efficient synthesis of (5-HOMe)dC containing DNA. Key steps of the synthesis are a palladium-catalyzed formylation and the simultaneous protection of a hydroxyl and amino group as a cyclic carbamate. DNA synthesis is possible under standard conditions, and deprotection can be carried out with dilute NaOH.",10.1021/ol102408t,2010-11-17,0.6280736208169259
Tetrahedron,Synthesis of biologically potent new 3-(heteroaryl)aminocoumarin derivatives via Buchwald–Hartwig C–N coupling,,10.1016/j.tetlet.2009.12.089,2009-12-24,0.6280709823034757
Journal of Organic Chemistry,A Protecting-Group-Free Synthesis of Hagen’s Gland Lactones,"A practical protecting group free synthesis of Hagen's gland lactones 1 and 2 is accomplished in four steps and 25.6 and 37.4% overall yields, respectively. The strategy relies on a one-pot conversion of D-glucono-δ-lactone to β-hydroxy-γ-vinyl-γ-lactone, cross-metathesis, and iodocyclization-deiodinization as key steps.",10.1021/jo301465z,2012-09-25,0.6280599028011628
Journal of Organic Chemistry,Enantioselective Total Syntheses of Plectosphaeroic Acids B and C,"Evolution of the synthetic strategy that culminated in the first total syntheses of the structurally unique plectosphaeroic acids B (2) and C (3) is described. The successful enantioselective route to (+)-2 and (+)-3 proceeds in 6 and 11 steps from the known hexahydro-2H-pyrazinopyrrolo[2,3-b]indole-1,4-dione 39, which in turn is available in enantiomerically pure form by chemical synthesis. The central challenge in this synthesis endeavor was uniting the hexahydro-2H-pyrazinopyrrolo[2,3-b]indole-1,4-dione and cinnabarinic acid fragments of these marine alkaloids. Critical for achieving this successful C-N bond formation was the use of an iodocinnabarinic acid diester in which the amino group was masked with two Boc substituents, a Cu(I) carboxylate complex and the weak base KOAc. The highly congested C-N bond generated in this coupling, in conjunction with the delicate nature of the densely functionalized coupling partners, provided a striking testament to the power of modern copper-mediated amination methods. Two approaches, one stereoselective, for introducing the methylthio substituents of (+)-plectosphaeroic acid B were developed. The epitrisulfide ring of (+)-plectosphaeroic acid C was formed by ring expansion of an epidisulfide precursor.",10.1021/jo4015479,2013-08-27,0.6280555454373472
Organic Process Research & Development,"Preparative Synthesis of an <i>R</i><sub>P</sub>-Guanosine-3′,5′-Cyclic Phosphorothioate Analogue, a Drug Candidate for the Treatment of Retinal Degenerations","High Resolution Image Download MS PowerPoint Slide Cyclic guanosine monophosphorothioate analogue 1a is currently showing potential as a drug for the treatment of inherited retinal neurodegenerations. To support ongoing preclinical and clinical work, we have developed a diastereoselective synthesis via cyclization and sulfurization of the nucleoside 5′- H -phosphonate monoester, which affords the desired R P -3′,5′-cyclic phosphorothioate in 9:1 ratio to the undesired S P -diastereomer. This route was made viable as a result of the silyl protection sequence used, which achieved >80% selectivity for 2′,5′-hydroxyls over 3′,5′-hydroxyls. Finally, the chromatography-free process allowed for a scale-up, as intermediates and the final product were isolated by crystallization to give 125 g of 1a (13.8% total yield) with over 99.9% HPLC purity.",10.1021/acs.oprd.1c00230,2021-10-19,0.6280533362363857
Journal of Organic Chemistry,Facile Synthesis of (±)-Paeonilide,"(+/-)-Paeonilide, a novel monoterpenoid metabolite from the roots of Paeonia delavayi showing anti-platelet activating factor activity, is convergently synthesized in five steps with 59% overall yield. The application of benzoyl peroxide-promoted radical addition of unsaturated ester to aldehyde and subsequent topologically favored cyclization greatly simplified the synthesis.",10.1021/jo0701278,2007-04-06,0.6280284465965783
Journal of the American Chemical Society,Concise Syntheses of (−)-Galanthamine and (±)-Codeine via Intramolecular Alkylation of a Phenol Derivative,"Suzuki coupling of 7 to 8 gave the biphenyl derivative 9. Reaction of 9 with ethyl vinyl ether/bromine/base gave 10, which on treatment with CsF/DMF at 130 degrees C resulted in the cross-conjugated 2,5-cyclohexadienone 6. Acid hydrolysis of 6 gave 11, which was reductively aminated to give (+/-)-narwedine 2. Since 2 has been converted into (-)-galanthamine 1 in two steps, this synthesis proceeds in eight steps with an overall yield of 63%. Also treatment of the cross-conjugated cyclohexadienone 6 with nitromethane/base gave 12, which was reduced to provide 13. Reduction of the nitro group in 13 to an amine, followed by reductive amination under acidic conditions, arrives at the codeine skeleton 15. Elaboration of 15 into (+/-)-codeine proceeds via the previously unknown alpha-epoxide derivative 18. This is the shortest synthesis of codeine (13 steps, 20% overall yield) and, for the first time, allows access to codeine without having to reduce codeinone.",10.1021/ja9085534,2009-10-16,0.6280282978936437
Journal of Organic Chemistry,An Improved Approach to Chiral Cyclopentenone Building Blocks. Total Synthesis of Pentenomycin I and Neplanocin A,"An improved approach to enantiomerically pure hydroxylated cyclopentenones is reported here, which involves intramolecular nitrone cycloaddition of sugar-derived chiral pent-4-enals and hex-5-en-ones-2 followed by N-O bond cleavage, quaternization of the amine thus produced, and finally oxidative elimination of the amino group. Synthesis of pentenomycin I and neplanocin A is described following this methodology.",10.1021/jo050987t,2005-07-16,0.6280281053553323
Organic Letters,Highly Stereodivergent Synthesis of Chiral C4-Ester-Quaternary Pyrrolidines: A Strategy for the Total Synthesis of Spirotryprostatin A,"In this work, we disclose two sets of highly diastereo- and enantioselective [3 + 2] cycloadditions of iminoesters with various α-substituted acrylates, especially for sterically hindered and weakly activated α-aryl or alkyl-substituted acrylates and alkenal, alkynal, or unstable aliphatic aldehyde-derived iminoesters, catalyzed by the AgHMDS/DTBM-Segphos or Ag 2 O/CA-AA-Amidphos catalytic system, achieving the stereodivergent synthesis of chiral C4-ester-quaternary exo - or endo -pyrrolidines with high yields and excellent diastereo- and enantioselectivities (up to >99:1 dr and >99% ee). More importantly, the gram-scale synthetic exo -adduct displays significant applications in the aspect of realizing the total synthesis of the spirotryprostatin A alkaloid via nine steps in a 36% overall yield.",10.1021/acs.orglett.3c00904,2023-05-10,0.6280150304974578
European Journal of Organic Chemistry,"A Carbohydrate Approach for the First Total Synthesis of Cochliomycin C: Stereoselective Total Synthesis of Paecilomycin E, Paecilomycin F and 6′‐<i>epi</i>‐Cochliomycin C","Abstract The first total synthesis of the chlorinated resorcylic acid lactone cochliomycin C is achieved starting from the readily available sugar D ‐lyxose. The strategy has also lead to the total synthesis of natural resorcylic acid lactones paecilomycin E, paecilomycin F and a synthetic analogue 6‐ epi ‐cochliomycin C. The key reactions include Ohira–Bestmann alkynylation, ring closing metathesis and regioselective methylation under Mitsunobu conditions.",10.1002/ejoc.201500395,2015-05-15,0.6280111291262982
Organic Process Research & Development,"Asymmetric Synthesis of the <i>cis</i>-1,2-Diaryltetralin Vepdegestrant Core via an Enantioselective Intramolecular Corey-Chaykovsky Epoxidation","An asymmetric synthesis of cis-1,2-diaryltetralin ( 2 ), a key chiral intermediate in the synthesis of Vepdegestrant ( 1 ), an orally available PROTAC being evaluated for the treatment of ER+/HER2- breast cancer, is reported. Chirality is initially introduced via a catalytic enantioselective intramolecular Corey-Chaykovsky epoxidation utilizing isothiocineole, a chiral sulfide. Although several asymmetric intermolecular epoxidations using chiral sulfides have been reported, our approach represents a unique intramolecular variant. The subsequent introduction of the cis-1,2-diaryl motif is achieved via diastereoselective hydrogenation.",10.1021/acs.oprd.4c00379,2024-11-08,0.6280043086906953
Journal of Organic Chemistry,Synthesis and Biological Profiling of Pyrazolo-Fused 7-Deazapurine Nucleosides,"A series of 8-substituted 1-methyl-1,4-dihydropyrazolo[3′,4′:4,5]pyrrolo[2,3- d ]pyrimidine (methylpyrazolo-fused 7-deazapurine) ribonucleosides have been designed and synthesized. Two synthetic approaches to the key heterocyclic aglycon 7, (i) a six-step classical heterocyclization starting from 5-chloro-1-methyl-4-nitropyrazole and (ii) a three-step cross-coupling and cyclization approach starting from the zincated 4,6-dichloropyrimidine, gave comparable total yields of 18% vs 13%. The glycosylation of 7 was attempted by three different methods but only the Vorbrüggen silyl-base protocol was efficient and stereoselective to give desired β-anomeric nucleoside intermediate 17A . Its nucleophilic substitutions or cross-coupling reactions at position 8 and deprotection of the sugar moiety gave eight derivatives of pyrazolo-fused deazapurine ribonucleosides, some of which were weakly fluorescent. Methyl, amino, and methylsulfanyl derivatives exerted submicromolar cytotoxic effects in vitro against a panel of cancer and leukemia cell lines as well as antiviral effects against hepatitis C virus in the replicon assay.",10.1021/acs.joc.0c00928,2020-07-21,0.6280030159517911
Journal of Organic Chemistry,An Enyne Cycloisomerization Approach to the Triple Reuptake Inhibitor GSK1360707F,The triple reuptake inhibitor GSK1360707F was synthesized via an efficient and scalable route that features an enyne cycloisomerization reaction catalyzed by either Pt(II) or Au(I). Key aspects of this work such as the choice of the nitrogen protecting group and initial enantioselectivity studies are discussed.,10.1021/jo102098y,2010-12-21,0.6279720793499673
Journal of Organic Chemistry,Perylenequinone Natural Products: Evolution of the Total Synthesis of Cercosporin,"The evolution of the first total synthesis of perylenequinone cercosporin is described. The key features developed during these efforts include a biscuprate epoxide alkylation, installation of the methylidene acetal, palladium-catalyzed O-arylation, and C3,C3'-decarbonylation. Due to the rapid atropisomerization of the helical axis of cercosporin (at 37 degrees C), the sequencing of these transformations was critical. To this end, the developed protocol enabled the formation of a key advanced intermediate on preparative scale absent any atropisomerization. Furthermore, the O-arylation proved to be general, and the strategy was used in an improved synthesis of a helical chiral perylenequinone structure.",10.1021/jo9013854,2009-11-09,0.6279715291172822
European Journal of Organic Chemistry,Preparation of a Key Tetraene Precursor for the Synthesis of Long Acenes,"The tetraene 7,7‐dimethoxy‐2,3,5,6‐tetramethylenebicyclo[2.2.1]heptane is a key compound for the preparation of a large variety of acenes protected by a carbonyl bridge. We report herein a medium scale preparation in seven steps of this valuable starting material. Diels–Alder addition between 6,6‐dimethtyl fulvene and maleic anhydride, followed by carboxylation, ozonolysis of the double bond, reduction of the four ester groups, then chlorination of the alcohol groups and dehydrochlorination give the target compound in 17 % overall yield.",10.1002/ejoc.201901868,2020-01-23,0.6279617733560288
Angewandte Chemie International Edition,A Concise and Flexible Synthesis of the Potent Anti‐Influenza Agents Tamiflu and Tamiphosphor,"Tamiflu and the highly potent neuraminidase inhibitor tamiphosphor have been synthesized in 11 steps and greater than 20 % overall yields from an haloarene (1S,2S)-cis-diol. The key transformations include a regio- and stereoselective bromoamidation, and a palladium-catalyzed carbonylation or phosphonylation reaction (see scheme; tamiflu: A=CO2Et, B=NH3+H2PO4−, tamiphosphor: A=PO(ONH4)2, B=NH2).",10.1002/anie.200801959,2008-07-09,0.6279600583458373
Synthesis,Strategy for the Assembly of Chiral Bicyclic Lactams: A Concise Synthetic Route to (-)-Coniceine,"A concise asymmetric synthesis of chiral bicyclic lactams combining a highly stereoselective 1,2-addition on SAMP hydrazones with a ring closure metathesis has been achieved. The synthetic utility of this approach has been emphasized by the total synthesis of (-)-coniceine in high enantiomeric excess.",10.1055/s-2008-1067204,2008-08-27,0.6279576311155263
Organic Letters,A New Cross-Coupling-Based Synthesis of Carpanone,Carpanone has been stereoselectively synthesized in 55% yield and six steps from sesamol. The key step of the synthetic sequence is the direct introduction of the propenyl side chain via a Suzuki-Miyaura cross-coupling reaction. The subsequent Pd(II)-catalyzed oxidative coupling yields carpanone as a single diastereoisomer independently of the geometric configuration of the starting precursor. A new mechanism is proposed for this transformation.,10.1021/ol9017326,2009-09-02,0.6279561614783649
Synthesis,Divergent Syntheses of Carbazole Alkaloids,"Starting from common intermediate methyl 1-hydroxy-9H-carbazole-3-carboxylate, synthetic routes toward murrayaquinone A, olivacine, and N-methylcalothrixin B were developed.",10.1055/s-0037-1610185,2018-07-05,0.6279478612838444
Organic Process Research & Development,"Process Improvements in the Synthesis of 2,4,5-Trifluorobenzoic Acid. Selective Hydrodefluorination of Tetrafluorophthalimides","An improved preparation of the fluoroquinolone antibacterial intermediate 2,4,5-trifluorobenzoic acid is described. A combination of a selective hydrodefluorination and hydrolysis reaction of 3,4,5,6-tetrafluoro- N -methylphthalimide leading to 3,5,6-trifluorophthalic acid was key to the success of the process. In addition the development of a two-step, one-pot imidization/halogen exchange from tetrachlorophthalic anhydride to 3,4,5,6-tetrafluoro- N -methylphthalimide in sulfolane solvent is detailed.",10.1021/op970244c,1998-02-14,0.6279455119614311
Synthesis,"Synthesis of d-Fagomine and Its Seven- and Eight-Membered Higher-Ring Analogues, and the Formal Synthesis of (+)-Australine from l-Xylose-Derived Chiron","The synthesis of d -fagomine and its seven- and eight-membered higher-ring analogues from commercially available l -xylose is reported. The syntheses involve elaboration of a common alkenol precursor obtained from l -xylose-derived hemiacetal. The key steps in the syntheses are intramolecular reductive amination and ring-closing metathesis for the synthesis of d -fagomine and seven-/eight-membered iminosugar, respectively. We have also extended our synthetic strategy for the formal synthesis of (+)-australine using zinc-mediated fragmentation reaction and ring-closing metathesis as key steps.",10.1055/s-0035-1562438,2016-06-29,0.6279433066221732
Synthesis,"Synthesis of 4-Aryl-4-methyl- and 4,4-Dimethyl-4H-pyrrolo[2,1-c][1,4]benzothiazines by an Easy Five-Step Sequence Starting from 2-Sulfanylbenzenamines","A convenient process for the synthesis of 4-aryl-4-methyl- and 4,4-dimethyl-4 H -pyrrolo[2,1- c ][1,4]benzothiazines has been developed. Cyclization of 1-{2-[1-aryl(or methyl)ethenylsulfanyl]phenyl}pyrroles, which are readily obtained by an easy four-step sequence starting from commercially available 2-sulfanylbenzenamines, to the desired heterocycles can be effected in good to excellent yields on treatment with a catalytic amount of hydriodic acid.",10.1055/s-0032-1316769,2012-08-21,0.6279404404680001
Synthesis,"A Convenient Synthesis of Dithieno[3,2-b:2′,3′-d]thiophenes from Thiophene","A new synthetic method for dithieno[3,2- b :2′,3′- d ]thiophenes was developed. The approach involves three steps starting from thiophene: tetraiodation of thiophene, selective dialkynylations on the 2,5-positions of the tetraiodothiophene, and finally CuI/TMEDA catalyzed double annulations of 2,5-dialkynyl-3,4-diiodothiophenes by Na 2 S, to afford dithieno[3,2- b :2′,3′- d ]thiophene and its derivatives.",10.1055/s-0035-1562531,2016-08-24,0.6279328452404083
Organic Letters,Total Synthesis of Leupyrrin B<sub>1</sub>: A Potent Inhibitor of Human Leukocyte Elastase,"The total synthesis of leupyrrin B1 was accomplished by an expedient strategy that involves an optimized HATU-mediated amide coupling protocol of elaborate substrates. The generally useful procedure was also successfully applied in an improved total synthesis of leupyrrin A1. Finally, leupyrrins A1 and B1 were evaluated toward a panel of proteases, and human leukocyte elastase was discovered as a molecular target of the leupyrrins.",10.1021/acs.orglett.6b01724,2016-08-03,0.6279290593133526
Synthesis,<i>meta</i>-Selective Aromatic Borylation as Key Step in the Synthesis of Poipuol,A synthesis of the marine natural product poipuol is reported. The key reaction sequence consists of an iridium-catalyzed meta-selective CH-borylation followed by the conversion of the resulting arylboronic ester into an aryl chloride.,10.1055/s-2008-1078449,2008-06-11,0.6279254706955543
Journal of Organic Chemistry,Total Syntheses of (+)-Fawcettimine and (+)-Lycoposerramine-B,"The total synthesis of (+)-fawcettimine was completed in a highly stereoselective manner starting from the oxatricyclo[7.3.0.0(1,5)]dodecanedione derivative. The crucial step in this total synthesis involves the efficient construction of the azonane framework by the intramolecular Mitsunobu reaction. Furthermore, the first total synthesis of (+)-lycoposerramine-B was also accomplished via the common synthetic intermediate.",10.1021/jo100499h,2010-04-26,0.6279237992608682
Synthesis,"Unified Approach for the Total Synthesis of Bis-THF C15 Acetogenins: A Chloroenyne from Laurencia majuscula, Laurendecumenyne B and Laurefurenynes A/B","Abstract A highly diastereoselective total synthesis of several bis-THF C15 acetogenin natural products, chloroenyne from Laurencia majuscula, laurendecumenyne B, and laurefurenynes A/B, is reported. Additionally the synthesis of an advanced intermediate reported in the earlier total synthesis of (E/Z)-elatenynes (formal synthesis) is described. The salient features in the synthesis include epoxide opening, Birch reduction, Sharpless asymmetric dihydroxylation-cycloetherification, SN2 halo­genation, and a relay cross metathesis.",10.1055/a-1500-1407,2021-05-05,0.6279191685636183
Journal of Organic Chemistry,"Concise and Enantioselective Total Synthesis of 15-Deoxy-Δ<sup>12,14</sup>-Prostaglandin J<sub>2</sub>","The concise and enantioselective synthesis of 15-deoxy-Δ(12,14)-prostaglandin J(2) (15d-PGJ(2)) has been accomplished in 11 steps from a known alcohol. The key step of the synthesis involves an asymmetric Rh-catalyzed cycloisomerization of ene-ynone, followed by an olefin isomerization.",10.1021/jo101523k,2010-10-08,0.6279167473685973
Synthesis,Synthesis of Ledipasvir through a Late-Stage Cyclopropanation and Fluorination Process,"Abstract We have designed and developed an easily accessible advanced intermediate of ledipasvir that allowed late-stage cyclopropanation and difluorination, thereby providing a novel and more efficient process for the preparation of ledipasvir in the longest linear sequence of 8 steps with 20% overall yield.",10.1055/s-0042-1751437,2023-04-13,0.6278958276226894
Tetrahedron,"Efficient synthesis of (−)-methyl 3-epi-shikimate and methyl 3-epi-quinate by one-pot selective protection of trans-1,2-diols",,10.1016/s0040-4039(00)01507-0,2000-11-01,0.6278848180660597
Tetrahedron,A formal synthesis of the syributins and secosyrins and a synthetic approach towards the syringolides,,10.1016/s0040-4039(98)01944-3,1998-11-01,0.6278787269026118
Synthesis,Synthesis the C1–C15 Fragment of Incednine,"Abstract We report on our progress towards the synthesis of the exotic, delicate, and tense polyketidic macrolactam of incednine. This work constitutes a significant advancement towards the total synthesis of a family of molecules of biological and medicinal interest. Some of the key features of this synthesis required evolutions from the initially designed strategy, leading to the use of a Horner–Wadsworth–Emmons olefination to build the C2–C9 tetraene. For this purpose, a polyfunctionalized phosphonate was used that was obtained through an unprecedented Pd-catalyzed cross-coupling involving the zinc salt of diethyl methylphosphonate. The resulting desired C1–C15 fragment displays a carboxylic acid ester at C1 and a vinyl iodide at C15, both functions being ready for subsequent amide coupling with the C16–C23 fragment and final Suzuki cyclization, respectively.",10.1055/a-2464-7068,2024-11-08,0.6278760911673267
Organic Letters,Asymmetric Synthesis of the Chlorocyclopropane-Containing Callipeltoside A Side Chain,"[reaction: see text] The callipeltoside A chlorocyclopropyl-containing dienyne side chain has been synthesized in nine steps and 33% overall yield from commercially available 1,2,5,6-O-dicyclohexylidene-D-mannitol. The key steps in the synthesis are a highly diastereoselective cyclopropanation of a vinyl chloride allylic ether and a Suzuki cross-coupling to complete the carbon framework.",10.1021/ol0155182,2001-01-31,0.6278628639366334
Organic Process Research & Development,"Development of an Enantioselective Novozym 435 Mediated Acetylation for the Preparation of (1<i>S</i>,3<i>R</i>)-3-Acetamidocyclohexane-1-carboxylic Acid","Starting from a cheap and readily available starting material, a short and enantioselective route to (1 S,3 R )-3-acetamidocyclohexane-1-carboxylic acid was developed. The key steps were a rhodium catalyzed hydrogenation of 3-aminobenzoic acid and an enantioselective Novozym 435 mediated acetylation of racemic isopropyl 3-aminocyclohexanecarboxylate.",10.1021/acs.oprd.6b00146,2016-06-16,0.6278627064331982
Organic Letters,"Heteroannulation of Nitroketene <i>N,S</i>-Arylaminoacetals with POCl<sub>3</sub>:  A Novel Highly Regioselective Synthesis of Unsymmetrical 2,3-Substituted Quinoxalines","[reaction: see text]. A novel regioselective route for the synthesis of substituted and fused 3-chloro-2-(methylthio)quinoxalines through POCl3-mediated heteroannulation of a range of alpha-nitroketene N,S-anilinoacetals has been reported.",10.1021/ol0505095,2005-04-30,0.6278622028243089
Organic Letters,Total Synthesis of (±)-Symbioimine,"The synthesis of (+/-)-symbioimine (1) has been completed in only 12 linear steps in 8% overall yield. The key step is the treatment of 13b with BF3.Et2O to generate N-carboalkoxydihydropyridinium cation 14b, which undergoes a novel stereospecific intramolecular Diels-Alder reaction to give adduct 16b in 42% yield. Cleavage of the N-Troc group of 16b afforded imine 24b stereospecifically. Cleavage of the TBDMS ethers and sulfation provided (+/-)-symbioimine (1). [reaction: see text].",10.1021/ol062333s,2006-11-01,0.6278596335924905
European Journal of Organic Chemistry,Baylis–Hillman Acetates in Synthesis: Copper(I)/<i>tert</i>‐Butyl Hydroperoxide Promoted One‐Pot Oxidative Intramolecular Cyclization Protocol for the Preparation of Pyrrole‐Fused Compounds and the Formal Synthesis of (±)‐Crispine A,"Abstract A convenient one‐pot protocol for the synthesis of benzo‐fused and indole‐fused indolizines from Baylis–Hillman acetates was developed. This strategy involves CuBr/ tert ‐butyl hydroperoxide promoted oxidation, intramolecular cyclization, and aromatization as key steps. The efficacy of this methodology was demonstrated by the formal synthesis of (±)‐crispine A, a biologically active molecule.",10.1002/ejoc.201600384,2016-04-29,0.6278555546774163
Tetrahedron,Asymmetric synthesis of a nitroalkane by the use of novel nitroalkene reductases from baker's yeast,,10.1016/s0040-4039(01)00464-6,2001-05-01,0.6278530527444152
Organic Letters,"Biomimetic Total Syntheses of Callistrilones A, B, and D","A biomimetic total syntheses of antibacterial natural products (±)-callistrilones A, B, and D, the first triketone-phloroglucinol-monoterpene hybrids with an unprecedented [1]benzofuro[2,3-a]xanthene and [1]benzofuro[3,2-b]xanthene pentacyclic ring system along with the postulated biosynthetic intermediate, isolated from the leaves of Callistemon rigidus, were achieved. The total synthesis features highly regio- and diastereoselective catalytic Friedel-Crafts alkylation, palladium-catalyzed Wacker-type oxidative cyclization, Michael addition, and late-stage diastereoselective epoxide formation from the extremely hindered β face as key steps.",10.1021/acs.orglett.7b03815,2018-01-17,0.6278491355355541
Journal of the American Chemical Society,Total Synthesis of (+)-Scholarisine A,"An effective total synthesis and assignment of the absolute configuration of the architecturally challenging compound (+)-scholarisine A has been achieved via a 20-step sequence. Highlights include a reductive cyclization involving a nitrile and an epoxide, a modified Fischer indole protocol, a late-stage oxidative lactonization, and an intramolecular cyclization leading to the indolenine ring system of (+)-scholarisine A.",10.1021/ja211840k,2012-01-25,0.6278361635922844
Tetrahedron,An improved general synthetic approach to cis-clerodane diterpenoids. A more efficient total synthesis of (±)-6β-acetoxy-2-oxokolavenool,,10.1016/s0040-4039(01)00706-7,2001-06-01,0.6278354151082683
Journal of Organic Chemistry,Toward the Total Synthesis of Scabrosins: Synthesis of a Desulfur-scabrosin Skeleton and Its Stereoisomers,"The enantioselective synthesis of a desulfur-scabrosin skeleton was reported. The synthesis began from 3-(hydroxymethyl)phenol, and key steps include asymmetric nucleophilic epoxidation, a Mitsunobu reaction using a sulfonamide as the nucleophile, the construction of a pyrrolidine ring by intramolecular nucleophilic substitution, and inversion of configuration through base-induced keto-enol isomerization. Additionally, two isomers of the carbon skeleton were also obtained via an alternative ring-closing strategy.",10.1021/acs.joc.9b00015,2019-03-22,0.6278323695364154
Synthesis,"A New, Improved and Convenient Synthesis of 4H-Cyclopenta[2,1-b:3,4-b′]-dithiophen-4-one","A new and efficient three-step synthesis of 4H-cyclopenta[2,1-b:3,4-b′]dithiophen-4-one (CDT) (1) is described. This was achieved by a one-pot, regiospecific synthesis of bis(2-iodo-3-thienyl)methanol (13), its subsequent oxidation to the bis(2-iodo-3-thienyl) ketone (14) which after Ullmann coupling yielded the title compound 1.",10.1055/s-2002-31958,2002-01-01,0.6278251131209948
Journal of Organic Chemistry,Convergent Strategy to Dizocilpine MK-801 and Derivatives,"A convergent total synthesis of MK-801 has been achieved. Key synthetic transformations include a multicomponent Barbier-type reaction to construct the α-branched amine, a selective Heck α-coupling tactic to generate the exocyclic alkene skeleton, and a late-stage intramolecular hydroamination reaction between the exocyclic alkene and the secondary protected amine. The efficacy of this method was demonstrated by the synthesis of two news analogues substituted on the aromatic rings.",10.1021/acs.joc.8b00305,2018-02-28,0.6278233396017862
Journal of Organic Chemistry,Efficient Desymmetrization of “<i>Pseudo</i>”-<i>C</i><sub>2</sub>-Symmetric Substrates:  Illustration in the Synthesis of a Disubstituted Butenolide from Arabitol,"A short synthesis of the homochiral disubstituted butenolide 1 is described in four steps from arabitol. The key steps are the selective kinetic protection of arabitol and the cyclization of 11 to form the butenolide ring. This last transformation represents a rare example of a fully stereoselective cyclitive desymmetrization process of a ""pseudo""-C2-symmetric substrate.",10.1021/jo026696r,2003-02-01,0.6278214825673651
Journal of Organic Chemistry,"Development of a Scalable, Chromatography-Free Synthesis of <i>t</i>-Bu-SMS-Phos and Application to the Synthesis of an Important Chiral CF<sub>3</sub>-Alcohol Derivative with High Enantioselectivity Using Rh-Catalyzed Asymmetric Hydrogenation","A chromatography-free, asymmetric synthesis of the C2-symmetric P-chiral diphosphine t-Bu-SMS-Phos was developed using a chiral auxiliary-based approach in five steps from the chiral auxiliary in 36% overall yield. Separtion and recovery of the auxiliary were achieved with good yield (97%) to enable recycling of the chiral auxiliary. An air-stable crystalline form of the final ligand was identified to enable isolation of the final ligand by crystallization to avoid chromatography. This synthetic route was applied to prepare up to 4 kg of the final ligand. The utility of this material was demonstrated in the asymmetric hydrogenation of trifluoromethyl vinyl acetate at 0.1 mol % Rh loading to access a surrogate for the pharmaceutically relavent chiral trifluoroisopropanol fragment in excellent yield and enantiomeric excess (98.6%).",10.1021/acs.joc.7b03022,2018-01-11,0.6278203322969464
Synlett,Concise Synthesis of (±)-Smenochromene D (= Likonide B)<sub />,"The total synthesis of smenochromene D, an unusual ansa-terpenoid is described. The synthesis features an unprecedented macrocyclization proceeding through a biomimetic electrocyclization. The enantiomeric relationship between smenochromene D and likonide B is established.",10.1055/s-2005-863713,2005-01-01,0.627819325904002
Chemical Science,Meeting key synthetic challenges in amanitin synthesis with a new cytotoxic analog: 5′-hydroxy-6′-deoxy-amanitin,Elucidating a highly diastereoselective sulfoxidation of <italic>S</italic> -deoxy-amanitin to afford α-amanitin and a more synthetically accessible analog of near-native toxicity.,10.1039/d0sc04150e,2020-01-01,0.6277977894736915
Organic Letters,New Synthesis of Vaulted Biaryl Ligands via the Snieckus Phenol Synthesis,"[reaction: see text] In an effort to develop a synthesis of the VAPOL ligand that avoids the use of a chromium carbene complex, a route was examined that involved the annulation of a naphthalene carboxamide via the method of Snieckus. The latter derivatives could be converted in a two-step sequence to 2-phenyl-4-phenanthrols in 60-72% overall yields. The utility of this method for the synthesis of VAPOL derivatives is demonstrated in the synthesis of (S)-7,7'-dimethyl-VAPOL.",10.1021/ol047852e,2005-01-08,0.6277955521266
Organic Process Research & Development,Improved Scale-up Synthesis and Purification of Clinical Asthma Candidate MIDD0301,"We report an improved and scalable synthesis of MIDD0301, a positive GABA A receptor modulator that is under development as oral and inhaled treatments for asthma. In contrast to other benzodiazepines in clinical use, MIDD0301 is a chiral compound that has limited brain absorption. The starting material to generate MIDD0301 is 2-amino-5-bromo-2′-fluorobenzophenone, which has a nonbasic nitrogen due to electron-withdrawing substituents in the ortho and para positions, reducing its reactivity toward activated carboxylic acids. Investigations of peptide coupling reagents on a multigram scale resulted in moderate yields due to incomplete conversions. Second, the basic conditions used for the formation of the seven-membered 1,4-diazepine ring resulted in racemization of the chiral center. We found that neutral conditions comparable to the p K a of the primary amine were sufficient to support the formation of the intramolecular imine but did not enable the simultaneous removal of the protecting group. Both difficulties were overcome with the application of the N -carboxyanhydride of d -alanine. Activated in the presence of an acid, this compound reacted with nonbasic 2-amino-5-bromo-2′-fluorobenzophenone and formed the 1,4-diazepine upon neutralization with triethylamine. Carefully designed workup procedures and divergent solubility of the synthesic intermediates in solvents and solvent combinations were utilized to eliminate the need for column chromatography. To improve compatibility with large-scale reactors, temperature-controlled slow addition of reagents generated the imidazodiazepine at −20 °C. All intermediates were isolated with a purity of >97% and impurities were identified and quantified. After the final hydrolysis step, MIDD0301 was isolated in a 44% overall yield and a purity of 98.9% after recrystallization. The enantiomeric excess was greater than 99.0%.",10.1021/acs.oprd.0c00200,2020-07-29,0.6277764222214961
Organic Letters,Total Synthesis of Callipeltoside A,A convergent total synthesis of cytotoxic marine macrolide callipeltoside A is described. The synthesis highlights two stereoselective [4 + 2] annulations for the preparation of associated pyran rings.,10.1021/ol0480325,2004-10-16,0.6277268719706581
Journal of Organic Chemistry,Furan Approach to Vitamin D Analogues. Synthesis of the A-Ring of Calcitriol and 1α-Hydroxy-3-deoxyvitamin D<sub>3</sub>,"The A-rings of calcitriol (1α,25-dihydroxyvitamin D(3)) and 1α-hydroxy-3-deoxyvitamin D(3) were synthesized using the furan approach. The critical steps in the synthesis of the A-ring of calcitriol involved an asymmetric carbonyl-ene reaction of 3-methylene-2,3-dihydrofuran with 3-(tert-butyldimethylsiloxy)propanal, a diastereoselective Friedel-Crafts hydroxyalkylation, an oxidation of the 2,3-disubstituted furan to give a γ-hydroxybutenolide, and a Peterson olefination. The A-ring (Z)-dienol of calcitriol was synthesized in 12 steps from 3-(tert-butyldimethylsiloxy)propanal in 17% yield.",10.1021/jo101155c,2010-09-16,0.6277085850332312
Organic Letters,A Highly Concise and Convergent Synthesis of HCV Polymerase Inhibitor Deleobuvir (BI 207127): Application of a One-Pot Borylation–Suzuki Coupling Reaction,"A highly concise and convergent synthesis of HCV polymerase inhibitor Deleobuvir (BI 207127, 1) was achieved, featuring efficient Pd-catalyzed one-pot borylation-Suzuki coupling where TFP was identified as the unique ligand effective for these transformations.",10.1021/ol5021114,2014-08-08,0.6277037843766559
Synlett,A Synthesis of Salinomycin. Part 1. Synthesis of Key Fragments,"All articles of this category Syntheses of the C11-C20 furan fragment 5 and the C21-C30 lactone fragment 6 en route to the polyether antibiotic salinomycin are described. Stereocontrol in the construction of 5 was accomplished via an asymmetric aldol reaction using an oxazolidinethione as a chiral auxiliary. Stereocontrol in the construction of 6 was accomplished by an asymmetric oxidation of a 1,5-diene with KMnO 4 to generate 4 stereogenic centres in a single step.",10.1055/s-1994-22870,1994-01-01,0.6276951180880912
Synthesis,First Enantioselective Synthesis of Aptazepine,"Aptazepine (2-methyl-1,3,4,14b-tetrahydro-2H,10H-pyrazino[1,2-a]pyrrolo[2,1-c][1,4]benzodiazepine), a potent tetracyclic antidepressant, was synthesized in both its enantiopure forms by using an asymmetric transfer hydrogenation in a key step. Reduction of the prochiral imine 7 gave the products (R)- and (S)-8 in 63% and 61% ee, respectively, but a single crystallization improved the enantiomeric purity to 98% ee. The final (R)- and (S)-aptazepines were prepared in four subsequent steps. The absolute configuration of intermediate (S)-8 was determined by X-ray crystallography.",10.1055/s-0031-1289646,2011-12-14,0.6276867554964588
Organic Letters,Total Synthesis of (−)-Amphidinolide P,"The convergent enantiocontrolled total synthesis of the 15-membered macrolactone (-)-amphidinolide P is reported. Key transformations include a Sakurai allylation, a Stille coupling for the formation of a fully functionalized acyclic precursor, and intramolecular transesterification.",10.1021/ol0000197,2000-03-17,0.6276829449793504
Organic Letters,Enantioselective Sequential Conjugate Addition−Allylation Reactions: A Concise Total Synthesis of (+)-Podophyllotoxin,"A highly flexible and concise total synthesis of (+)-podophyllotoxin featured with an enantioselective sequential conjugate addition-allylation reaction was reported. Starting from commercially available 3,4,5-trimethoxycinnamic acid, this new route leads to (+)-podophyllotoxin 1 in only eight steps with 29% overall yield.",10.1021/ol8026208,2008-12-23,0.6276810949668834
European Journal of Organic Chemistry,A <i>C</i><sub>2</sub>‐Symmetric Pool Based Flexible Strategy: An Enantioconvergent Synthesis of (+)‐Valiolamine and (+)‐Valienamine,"Abstract A new enantioconvergent strategy directed toward the synthesis of glucosidase inhibitors was developed by using a C 2 ‐symmetric element within the chiral pool and by applying an iodine‐promoted cyclization of an unsaturated carbonimidothioate for the regio‐ and diastereocontrolled installation of amino and hydroxy units. Not only does this simple flexible strategy provide a convergent concise approach to (+)‐valiolamine ( 1 ), but it can also be readily adopted for the synthesis of (+)‐valienamine ( 2 ). Commercially available and cheap C 2 ‐symmetric D ‐tartaric acid served as the chiral building block.",10.1002/ejoc.201101845,2012-03-30,0.6276789805246795
Tetrahedron,Synthesis and thermolysis of rimethylsilyl enol ethers of 2-norbornanones : an efficient route to cyclopentenones,,10.1016/s0040-4039(01)86471-6,1979-01-01,0.6276781438636562
Synthesis,Asymmetric Synthesis of the 9-Azabicyclo[3.3.1]nonane Core of Macroline-Type Alkaloids,"Abstract The signature indole-fused 9-azabicyclo[3.3.1]nonane (9-ABN) core of macroline-type alkaloids in its natural configuration has been accessed in 4 steps and 16% overall yield from 1H-indole and an l-menthyl nicotinate-derived pyridyl alcohol. The two starting fragments were condensed using a hydrogen auto-transfer (HA) strategy. The key stereocenter at C-5 was installed in up to 95:5 dr with a double diastereoselective, chiral auxiliary-assisted asymmetric transfer hydrogenation (CAATHy). This selective partial reduction of the pyridine to the tetrahydropyridine set the stage for stereospecific formation of the bridged, bicyclic 9-ABN system via a novel superacid-mediated cycloisomerization reaction. Starting from indole and 6-(hydroxymethyl)nicotinate esters, this new strategy provides rapid, protecting group- and transition metal-free access to the tetracyclic macroline core.",10.1055/a-2779-1148,2025-12-25,0.6276767557037735
Organic Letters,Chemoenzymatic Approaches toward Dechloroansamitocin P-3,"[reaction: see text] The enantioselective total synthesis of proansamitocin, a key biosynthetic intermediate of the highly potent antitumor agent ansamitocin P-3, is described which bears a diene-ene RCM as the key macrocyclization step. Feeding of proansamitocin to an AHBA block mutant Actinosynnema pretiosum (HGF073) yielded ansamitocin P-3 as well as dechloroansamitocin P-3, the latter also being formed upon fermentation in the presence of 3-amino-5-methoxybenzoic acid.",10.1021/ol0702270,2007-03-23,0.6276663663567459
Organic Letters,Total Synthesis of Tipranavir Based on Iridium-Catalyzed Asymmetric Allylic Substitution of Dihydropyranone,"An efficient and highly enantioselective synthesis of tipranavir is realized based on an iridium-catalyzed asymmetric allylic substitution. High yield and diastereoselectivity (>20:1), as well as excellent enantioselectivity (99% ee ), were obtained for the key intermediate through direct asymmetric alkylation reaction of dihydropyranone with allylic tert -butyl carbonate. Anti-AIDS drug of tipranavir was finally accomplished in 8 steps and 6 pots starting from commercially available 1-phenyl-3-hexanone in 20.7% overall yield with 99% ee and >20:1 dr .",10.1021/acs.orglett.4c03736,2024-11-19,0.6276625204521972
European Journal of Organic Chemistry,"Synthetic Approaches to Ribosyl Adenosine 5′,5′′‐Diphosphate Fragment of Poly(ADP‐ribose)","Abstract Ribosyl adenosine 5′,5′′‐diphosphate is a poly(ADP‐ribose) fragment covalently bonded to a protein during post‐translational modification. Poly(ADP‐ribose) is involved in several biological processes such as DNA repair and cancerization. Herein, we report the development of two synthetic approaches to the poly(ADP‐ribose) fragment via a common precursor. The major difficulty in the synthesis of the fragment is the α‐(1′′→2′)‐glycosidic bond formation between the ribose and adenosine because of the lack of neighboring group participation and low reactivity of the 2′‐hydroxyl group. The first approach employed an indirect method that involved stepwise assembly of the ribosyl adenosine framework by O ‐ribofuranosylation of a commercially available ribose acceptor and subsequent N ‐glycosylation of N 6 ‐benzoyl adenine (14 linear longest sequence (LLS) steps, 11 pots, 6.8 % overall yield). In the second approach, the direct O ‐ribofuranosylation of a known 6‐chloropurine riboside acceptor was adopted (12 LLS steps, 10 pots, 4.8 % overall yield). Thus, two practical synthetic approaches to the target fragment were successfully established in terms of the number of LLS steps, pots, and overall yield. Furthermore, the precursor was converted into a conjugation‐ready building block, primed for application in ADP‐ribose oligomer synthesis.",10.1002/ejoc.202300875,2023-09-23,0.6276476557306968
Synthesis,Enantioselective Synthesis of (R)-Tiagabine via Asymmetric Hydrogen Atom Transfer Protocol,"Abstract An enantioselective synthesis of tiagabine has been achieved utilizing an asymmetric hydrogen atom transfer protocol to construct its essential chiral tertiary carbon center. A cyclization reaction via double N-substitution is tactically orchestrated as the other key step to install the crucial alkaloid ring. Compared with the previous synthetic strategy, which used commercially available nicotinate as the starting material to ensure a short synthetic route, this strategy uses a readily modifiable and accessible alkyl-substituted acrylate as the starting material and thus provides a scenario for the facile synthesis of analogues and derivatives of tiagabine for further biological research.",10.1055/a-2039-6180,2023-02-21,0.6276408189014646
Synthesis,Stereoselective Total Synthesis of Achaetolide from l-Malic Acid,"A convergent total synthesis of achaetolide is described. The key steps include a Horner-Wadsworth-Emmons olefination, CBS reduction to install the stereochemistry at the C9 center, ste­reoselective vinylation to introduce the chiral center at C6, and finally­ a ring-closing metathesis (RCM) reaction to construct the ten-membered lactone of the molecule.",10.1055/s-0030-1260174,2011-08-16,0.6276252588061562
Synlett,An Expeditious Enantiospecific Synthesis of (+)-2-Hydroxy-<i>exo</i>-brevicomin,An expeditious approach for the synthesis of Western pine beetle pheromone 2-hydroxy-exo-brevicomin from natural chiral pool l-(+)-tartaric acid was achieved. The key step involves a highly diastereoselective reduction of a keto-Weinreb amide and further elaboration to the title compound in high yields with complete stereocontrol.,10.1055/s-2006-948190,2006-08-01,0.6276215526046585
Synlett,Concise Total Synthesis of Crambescin B Methyl Ester,"Abstract In this study, a concise total synthesis of crambescin B methyl ester, a cyclic guanidine alkaloid, has been achieved. The key aspects of this new approach include (1) A Mannich reaction between an α-amidosulfone and a β-keto ester to construct the main scaffold, and (2) acid-catalyzed dehydrative cyclization, leading to an enol ether in a highly stereoselective manner. This synthetic approach is nine steps shorter than our previously published method.",10.1055/a-2499-3635,2024-12-09,0.6276121896388186
Tetrahedron,A carbenoid route to C(1)–C(11) bridged steroids,,10.1016/s0040-4039(00)97016-3,1990-01-01,0.6276097225487071
European Journal of Organic Chemistry,"Synthesis of the Fungal Lipo‐Chitooligosaccharide Myc‐IV (C16:0, S), Symbiotic Signal of Arbuscular Mycorrhiza","Abstract A new synthesis of the fungal lipo‐chitooligosaccharide Myc‐IV (C16:0, S), which was recently reported to be a major symbiotic signalling molecule in arbuscular mycorrhiza, is described. Key steps include the oxidative cleavage of a 4,6‐ O ‐benzylidene acetal to prepare a disaccharidic glycosyl acceptor, and stereoselective glycosylations with 2‐methyl‐5‐ tert ‐butylphenyl thioglycosyl donors.",10.1002/ejoc.201301015,2013-09-19,0.6276069921437153
Angewandte Chemie International Edition,A Concise and Flexible Total Synthesis of (−)‐Diazonamide A,"The remarkable action of an IIII species on a tripeptide containing acyclic tyrosine/tryptophan is the key step in a total synthesis of (−)-diazonamide A. The completed preparation of this new antimitotic is concise, multiply convergent, and amenable to diversification of intermediates.",10.1002/anie.200352577,2003-10-14,0.6276036923962673
Journal of Organic Chemistry,Total Synthesis of Asterredione,"The first total synthesis of asterredione was efficiently accomplished over five linear steps and in 21.5% overall yield. As the crucial step, the 2-quaternary 1,3-cyclopentenedione skeleton of asterredione was readily achieved using the Darzens/ring-expansion strategy developed in our laboratory. The structure of synthesized asterredione was fully confirmed by X-ray crystallography.",10.1021/jo4028177,2014-02-11,0.6275897993650615
Journal of the American Chemical Society,Asymmetric Synthesis of Chiral Sulfoximines via the <i>S</i>-Arylation of Sulfinamides,"Optically active sulfoximines are a promising substance in medicinal chemistry. However, a methodology for preparing chiral sulfoximines in a stereoselective manner has been underdeveloped. Here, we report an asymmetric synthesis of chiral sulfoximines having an aryl group by the newly developed sulfur-selective arylation of easily accessible chiral sulfinamides. The utility of the present method is demonstrated by the asymmetric synthesis of a key intermediate of a COX-2 inhibitor.",10.1021/jacs.9b11298,2019-11-18,0.6275804176692712
Angewandte Chemie International Edition,An Unexpected Transannular [4+2] Cycloaddition during the Total Synthesis of (+)‐Norcembrene 5,"We report a concise and versatile total synthesis of the diterpenoid (+)-norcembrene 5 from simple building blocks. Ring-closing metathesis and an auxiliary-directed 1,4-addition are the key steps of our synthetic route. During the synthesis, an unprecedented, highly oxidized pentacyclic structural motif was established from a furanocembranoid through transannular [4+2] cycloaddition.",10.1002/anie.201912613,2019-11-21,0.6275749270768997
Journal of Organic Chemistry,A New Approach to (−)-Swainsonine by Ruthenium-Catalyzed Ring Rearrangement,"A new enantioselective synthesis of the idolizidine alkaloid (-)-swainsonine 1 in 40% overall yield starting from the known oxazolidinone 6 is described. Throughout the synthesis, the high efficiency of metal-catalyzed reactions is illustrated. The key step is a new ruthenium-catalyzed metathesis rearrangement reaction. In this ring-closing/ring-opening tandem process, stereocenters are transferred from a ring to the olefinic side chain of the formed heterocycle. The metathesis precursor was obtained by palladium-catalyzed desymmetrization of cyclopentenediol. The synthesis was completed by functionalization of the terminal double bond, cyclization of the second ring, and diastereoselective dihydroxylation.",10.1021/jo025589u,2002-05-15,0.6275714470704511
Journal of Organic Chemistry,A Route to 2-Substituted 3-Cyanopyrroles: Synthesis of Danaidal and Suffrutine A,"The title compounds were prepared in a two-step sequence from 4,4-dimethoxybutyronitrile and the respective esters by Claisen condensation and subsequent Paal-Knorr pyrrole synthesis. The sequence could be performed as a one-pot procedure delivering the pyrroles in yields of 47-72% over two steps (13 examples). Intramolecular variants of the method were applied to the total synthesis of danaidal and suffrutine A from the respective trityl-protected ω-amino alkanoates.",10.1021/acs.joc.6b01298,2016-06-22,0.6275678394675652
Organic Letters,Asymmetric Synthesis of Scillascillin-Type Homoisoflavonoid,The first asymmetric synthesis of a scillascillin-type homoisoflavonoid was reported. Key reactions for the asymmetric synthesis of benzocyclobutene include catalytic reductive desymmetrization of malonic ester and an intramolecular C-H activation of the methyl group.,10.1021/acs.orglett.3c03968,2024-01-19,0.6275622921092538
Organic Letters,Synthesis of (±)-Vibralactone,"Reductive alkylation of methyl 2-methoxybenzoate with prenyl bromide and hydrolysis afforded methyl 6-oxo-1-prenyl-2-cyclohexenecarboxylate. Reduction of the ketone, hydrolysis, iodolactonization, ozonolysis, and intramolecular aldol reaction provided a spiro lactone cyclopentenal. Retro-iodolactonization with activated Zn, formation of the beta-lactone, and reduction of the aldehyde completed an efficient first synthesis of (+/-)-vibralactone. No protecting groups were used except for the novel use of an iodolactone to protect both the prenyl double bond and carboxylic acid.",10.1021/ol800118c,2008-03-01,0.6275555637872889
Synthesis,An Efficient Preparation of 6-Alkoxy-substituted Benzocyclobutenones,"A short, efficient route to 3-alkoxybenzynes has been developed, starting from readily available compounds. This has enabled rapid access to 6-alkoxybenzocyclobutenones, which are valuable synthetic intermediates.",10.1055/s-2001-12767,2001-01-01,0.6275552721095113
Journal of Organic Chemistry,"Synthesis of 3-Hexahelicenol and Its Transformation to 3-Hexahelicenylamines, Diphenylphosphine, Methyl Carboxylate, and Dimethylthiocarbamate","A nonphotochemical synthetic route to 3-hexahelicenol is reported. It involves a key [2+2+2] cycloisomerization of CH(3)O-substituted triyne that is readily available from 1-methoxy-3-methylbenzene and 1-bromo-2-(bromomethyl)naphthalene. Further functional group transformations led to 3-CO(2)CH(3), 3-NH(2), 3-PPh(2), and 3-SC(O)N(CH(3))(2) substituted hexahelicenes.",10.1021/jo034369t,2003-05-24,0.6275532236779012
Organic Letters,FeCl<sub>3</sub> Catalyzed Prins-Type Cyclization for the Synthesis of Highly Substituted Indenes: Application to the Total Synthesis of (±)-Jungianol and <i>epi</i>-Jungianol,"A novel approach was developed for the synthesis of highly substituted indene derivatives, using an FeCl(3) catalyzed Prins-type cyclization reaction which was further applied in the total synthesis of jungianol and epi-jungianol.",10.1021/ol3032347,2013-01-14,0.6275441456498367
Tetrahedron,An efficient one-pot synthesis of novel 4-aryl-1-methyloxindoles,,10.1016/j.tetlet.2006.04.103,2006-05-19,0.6275307453214798
Angewandte Chemie International Edition,The Total Synthesis of the Fungal Metabolite Diversonol,Mission accomplished. The fungal metabolite diversonol has been synthesized for the first time. A key step in the total synthesis was the domino oxa-Michael–aldol condensation of salicylic aldehyde 1 and 4-hydroxycyclohexenone (2) that afforded the tricyclic scaffold of the target compound.,10.1002/anie.200502913,2005-12-09,0.6275075687873818
Angewandte Chemie International Edition,A Three-Step Synthesis of Halomon,"Markovnikov-type bromochlorinations of myrcene are the key to a very concise and straightforward synthesis of halomon (see scheme), a novel antitumor agent.",10.1002/1521-3773(20001002)39:19<3430::aid-anie3430>3.0.co;2-3,2000-10-02,0.6274939732476528
Journal of Organic Chemistry,"Divergent Total Synthesis of Triptolide, Triptonide, Tripdiolide, 16-Hydroxytriptolide, and Their Analogues","A divergent route was developed for the formal total synthesis of triptolide, triptonide, and tripdiolide, as well as a total synthesis of 16-hydroxytriptolide and their analogues in an enantioselective form. Common advanced intermediate 5 was concisely assembled by employing an indium(III)-catalyzed cationic polycyclization reaction and a palladium-catalyzed carbonylation-lactone formation reaction as key steps. This advanced intermediate was readily converted to the above natural products by using palladium-catalyzed cross-coupling or the Claisen rearrangement reaction as key steps. Additionally, preliminary structure-cytotoxic activity relationship studies of C13 suggested that it might be a new modification site that could still retain the cytotoxicity.",10.1021/jo501744j,2014-10-08,0.627491799875341
Organic Letters,Toward the Total Synthesis of Variecolin,"[reaction: see text] An annulative approach toward the total synthesis of the sesterterpenoid variecolin (1) is presented. Synthesis of the key hemiketal, containing the core ABC ring skeleton, has been achieved on a model system by an expeditious route utilizing samarium(II) iodide. Furthermore, enantioselective syntheses of component fragments for the total synthesis have been developed.",10.1021/ol015763l,2001-06-28,0.6274802428846463
Synlett,Efficient Enantioselective Total Synthesis of (+)-Helianane,"The enantiocontrolled total synthesis of (+)-helianane, a marine-derived heterocyclic sesquiterpene, has been accomplished with an efficient chirality transfer during the Me3Al-mediated aromatic Claisen rearrangement and a ring-closing metathesis as the key steps. The absolute structure of the natural product has been firmly established by total synthesis.",10.1055/s-0030-1260532,2011-04-20,0.627474441117054
Journal of the American Chemical Society,Enantioselective Total Synthesis of (+)-Testudinariol A Using a New Nickel-Catalyzed Allenyl Aldehyde Cyclization,"An enantioselective total synthesis of (+)-testudinariol A was completed. A new nickel-catalyzed allenyl aldehyde cyclization was developed in the approach. In addition, an asymmetric anti aldol reaction and a two-directional oxocarbenium ion/vinyl silane condensation were employed as key steps.",10.1021/ja027148y,2002-07-18,0.6274626068356455
Synlett,Studies on the Synthesis of Bitungolides A-E: Synthesis of the C(1)-C(12) Fragment,"Synthesis of the core segment of bitungolides A-E has been achieved in 17 steps and 4.7% overall yield. Six stereogenic centers of bitungolides A-E were established via allylation, dihydroxylation, Myers alkylation, and Evans aldol reaction.",10.1055/s-2008-1078486,2008-06-11,0.6274574192084299
Organic Process Research & Development,Process Development and Scale Up of a Selective JAK3 Covalent Inhibitor PF-06651600,"A scalable process for PF-06651600 ( 1 ) has been developed through successful enabling of the first generation syntheis. The synthesis highlights include the following: (1) replacement of costly PtO 2 with a less expensive 5% Rh/C catalyst for a pyridine hydrogenation, (2) identification of a diasteroemeric salt crystallization to isolate the enantiomerically pure cis-isomer directly from a racemic mixture of cis/trans isomers, (3) a high yielding amidation via Schotten–Baumann conditions, and (4) critical development of a reproducible crystallization procedure for a stable crystalline salt ( 1·TsOH ), which is suitable for long-term storage and tablet formulation. All chromatographic purifications, including two chiral SFC chromatographic separations, were eliminated. Combined with other improvements in each step of the synthesis, the overall yield was increased from 5% to 14%. Several multikilogram batches of the API have been delivered to support clinical studies.",10.1021/acs.oprd.9b00198,2019-07-19,0.6274568654775199
Tetrahedron,Studies toward the total synthesis of azaspiracids: synthesis of the FGHI ring domain,,10.1016/s0040-4039(03)01553-3,2003-08-01,0.6274017121538652
Synthesis,Synthesis of (R)-Coniine and (S)-Coinicine via Organocatalytic α-Aminoxylation of an Aldehyde,"A short and efficient synthesis of the indolizidine alkaloid (S)-coinicine has been achieved using organocatalytic sequential α-aminoxylation and Horner-Wadsworth-Emmons olefination of an aldehyde catalyzed by l-proline. Similarly, a common organocatalytic α-aminoxylation route has been developed for the asymmetric synthesis of both (R)-coniine and (S)-coinicine.",10.1055/s-0030-1257869,2010-07-22,0.6273906812588239
Organic Letters,Enantioselective Synthesis of (−)-Vallesine: Late-Stage C17-Oxidation via Complex Indole Boronation,"The first enantioselective total synthesis of (-)-vallesine via a strategy that features a late-stage regioselective C17-oxidation followed by a highly stereoselective transannular cyclization is reported. The versatility of this approach is highlighted by the divergent synthesis of the archetypal alkaloid of this family, (+)-aspidospermidine, and an A-ring-oxygenated derivative, (+)-deacetylaspidospermine, the precursor to (-)-vallesine, from a common intermediate.",10.1021/acs.orglett.8b01428,2018-06-04,0.6273894753669849
Journal of Organic Chemistry,Synthesis of Isohasubanan Alkaloids via Enantioselective Ketone Allylation and Discovery of an Unexpected Rearrangement,"A synthesis of the hasubanan alkaloids hasubanonine, runanine, and aknadinine via a unified route was attempted. Construction of key phenanthrene intermediates by a Suzuki coupling-Wittig olefination-ring-closing metathesis sequence allowed a convergent and flexible approach. Conversion of the phenanthrenes into the target structures was projected to involve six steps including phenolic oxidation, ketone allylation, anionic oxy-Cope rearrangement, and acid-promoted cyclization. The final step was thwarted by a pinacol-like rearrangement that delivered the unnatural isohasubanan alkaloid skeleton. The structures of the products were established by exhaustive NMR experiments and confirmed by GIAO (13)C NMR calculations of runanine, isorunanine, and three other isomers. These computations revealed some inconsistencies with the benzene solvent correction which suggest that caution should be used in employing this algorithm. The racemic synthesis of isohasubanonine was transformed into an enantioselective synthesis by the discovery that Nakamura's chiral bisoxazoline-ligated allylzinc reagent mediates the enantioselective allylation of ketone 19 in 93% ee. This method could be extended to three other structurally related ketones (92-96% ee), and the enantioselective syntheses of two other isohasubanan alkaloids, isorunanine and isoaknadinine, were accomplished. Racemic isohasubanonine was found to be an ineffective analgesic agent.",10.1021/jo802370v,2008-12-12,0.6273874979379623
Tetrahedron,"Water-mediated one-pot synthetic route for pyrazolo[3,4-b]quinolines",,10.1016/j.tetlet.2010.05.117,2010-06-02,0.6273820579554161
Tetrahedron,"Total syntheses of polyamine amides PhTX-4.3.3 and PhTX-3.4.3: Reductive alkylation is a rapid, practical route to philanthotoxins",,10.1016/0040-4039(95)01996-u,1995-12-01,0.6273757657345485
Journal of Organic Chemistry,Synthesis of <i>C</i><sub>2</sub>-Symmetric <i>gem</i>-Difluoromethylenated Angular Triquinanes,"A synthesis of symmetrical gem -difluoromethylenated angular triquinanes is described. The synthetic strategy involved sequential fluoride-catalyzed nucleophilic addition of PhSCF 2 SiMe 3 ( 1 ) to 2,2-diallylated or 2,2-dipropargylated indane-1,3-diones 2 followed by stereoselective radical cyclization of the resulting adducts 3 to provide the cyclized gem -difluoromethylenated diquinanes 4 as a mixture of stereoisomers. Repeated addition of 1 to 4 followed by cyclization resulted in the stereoselective synthesis of the desired C 2 -symmetric gem -difluoromethylenated angular triquinanes 6 in good yields with high stereoselectivity.",10.1021/acs.joc.7b02777,2017-12-08,0.6273629623261954
Journal of Organic Chemistry,Synthesis of Rapicone Based on Acyl Ketene–Alkyne Cycloaddition,"We report herein a concise route for the total synthesis of rapicone. The key strategy to form the ynone intermediate involves an Fe(III)/TEMPO-catalyzed aerobic oxidation of a 1,3-dihydroisobenzofuran moiety. This ether oxidation for the simultaneous installation of the keto aldehyde allowed the effective formation of the required ynone intermediate. The concise total synthesis of rapicone is substantiated by the unique formal [4 + 2] cycloaddition of acyl ketene with alkynone and is completed in 7 steps with 9.4% overall yield.",10.1021/acs.joc.4c02442,2024-11-20,0.6273600059774752
Journal of Organic Chemistry,Synthesis of Tetrahydroxyquinolizidines:  Ring-Expanded Analogs of the Mannosidase Inhibitor Swainsonine,"The indolizidine azasugar swainsonine ( 1 ) is an important inhibitor of mannosidase II and has shown antitumor and immunomodulatory activity. A comparison of the structure of swainsonine and d -mannopyranose shows that swainsonine lacks the C(4) hydroxymethine group of mannose. Ring-expanded quinolizidine analogs 4 of swainsonine were prepared where the “missing” hydroxymethine group was incorporated into the pyrrolidine ring of swainsonine between C(1) and C(8a). The quinolizidine analogs 4 resemble both d -mannopyranose and the related azasugar deoxymannojirimycin, a selective inhibitor of the glycoprotein processing enzyme mannosidase I. d -Arabinose was converted into the ω-halo azidoalkene 13, which was subjected to thermolysis, a strategy which had been successful in an earlier synthesis of swainsonine itself. Rather than the desired quinolizidine 4, the pyridinium ion 16 was produced. An alternate synthesis of all four C(9)/C(9a) diastereomers of 4 was developed which relied on the reductive double-alkylation of epoxides bearing remote azido and chloro groups. Thus, reduction of compounds 21 α, 21 β, 26, and 27 resulted in the formation of the quinolizidines 22, 23, 28, and 29, which were deprotected to give the quinolizidine analogs of swainsonine (9 S,9a R )- 4, (9 R,9a S )- 4, (9 S,9a S )- 4, and (9 R,9a R )- 4, respectively. An alternate synthesis of (9 R,9a R )- 4 involving the reductive N -alkylation of a cyclic imine was also developed. None of the quinolizidines showed significant glycosidase activity in screens against mannosidases, glucosidases, or fucosidases. Speculation on the significance of these findings is presented.",10.1021/jo960609b,1996-01-01,0.62735279658367
Organic Process Research & Development,"Improved and Practical Synthesis of 6-Methoxy-1,2,3,4- tetrahydroisoquinoline Hydrochloride","6-Methoxy-1,2,3,4-tetrahydroisoquinoline ( 1 ) or its hydrochloride salt ( 4 ) is an expensive chemical with limited commercial availability. We report an improved and practical synthesis of 4 from inexpensive 2-(3-methoxyphenyl)ethylamine ( 2 ) using a Pictet−Spengler condensation via a novel aminal intermediate. The synthesis significantly lowers the cost and provides easy access to 6-methoxy-1,2,3,4-tetrahydroisoquinoline or its HCl salt on a large scale.",10.1021/op7000468,2007-04-25,0.6273478375676285
Organic Letters,"Efficient Enantioselective Synthesis of Sertraline, a Potent Antidepressant, <i>via</i> a Novel Intramolecular Nucleophilic Addition to Imine","[formula: see text] An efficient enantioselective synthesis of sertraline, an antidepressant, utilizing anionic imine ring closure is described.",10.1021/ol990608g,1999-06-16,0.6273418318498573
Tetrahedron,"A novel in situ deprotection/coupling and iterative divergent/convergent strategy for the synthesis of oligo(1,4-phenyleneethynylene)s",,10.1016/j.tetlet.2005.10.113,2005-11-09,0.6273325580373265
Journal of Organic Chemistry,Stereoselective Total Syntheses of the Racemic Form and the Natural Enantiomer of the Marine Alkaloid Lepadiformine via a Novel <i>N</i>-Acyliminium Ion/Allylsilane Spirocyclization Strategy,"Stereoselective total syntheses of the racemic form and the natural enantiomer of the tricyclic marine alkaloid lepadiformine (6) have been accomplished using a novel intramolecular spirocyclization of an N-acyliminium ion with an allylsilane to form the A/C rings as the key step. Introduction of the hydroxymethyl group at C-13 of the racemic spirocycle 11 was achieved using our methodology for oxidative radical-based remote functionalization of o-aminobenzamides, followed by copper-catalyzed addition of Grignard reagent 16 to the N-acyliminium ion intermediate derived from 15. Subsequent Tamao oxidation of silane 17 then afforded the requisite hydroxymethyl compound 19, which was converted to the dimethyl acetal 25 via hydroformylation followed by aldehyde protection. Hydrolysis of the benzamide moiety of 25 and subsequent protection of the primary alcohol gave amino acetal 27. The synthesis was concluded from 27 by a four-step procedure: acid-catalyzed ring closure, amino nitrile formation, introduction of the hexyl chain by a Grignard reaction to an iminium salt, and removal of the O-benzyl protecting group to give (+/-)-lepadiformine (6). The enantioselective total synthesis of 6 started from known optically pure bromide 37, derived from (S)-pyroglutamic acid, and followed a similar sequence involving the key spirocyclization of N-acyliminium ion 42. This synthesis has established the absolute configuration of naturally occurring lepadiformine to be 2(R),5(S),10(S),13(S).",10.1021/jo0201070,2002-04-24,0.6273274959555417
Organic Letters,"A Biomimetic Strategy for the Synthesis of the Tricyclic Dibenzofuran-1,4-dione Core of Popolohuanone E","A concise synthesis of the complete tricyclic dibenzofuran-1,4-dione aromatic core of popolohuanone E has been demonstrated by mild base treatment of a biquinone intermediate, thus establishing a biomimetic route to this family of heterocyclic ring systems and the total synthesis of popolohuanone E.",10.1021/ol047825o,2004-12-14,0.6273140594564852
Organic Process Research & Development,Exploratory Process Development of a Novel Diacylglycerol Acyltransferase-1 (DGAT-1) Inhibitor,"A practical large-scale synthesis was developed for 1, a DGAT-1 inhibitor, involving an aza-Michael reaction, amidation, Dieckman cyclization, and conjugate addition of cyanamide followed by cyclization, to form the fused 4-amino-7,8-dihydropyrido[4,3- d ]pyrimidin-5-one scaffold. The enabled process presented here substantially improved safety (in particular, due to eliminating a nitration step and optimizing a high-energy intermediate step), reproducibility, and scalability, resulting in delivery of a multikilogram quantity of the API with high purity. The controls of API quality and particle size were also discussed.",10.1021/op400215h,2013-11-12,0.627308914776906
Synthesis,Synthetic Studies towards the Total Synthesis of Providencin,A synthetic approach to assemble the uncommon furylcyclobutane substructure in providencin has been developed starting from a commercially available cyclobutane precursor.,10.1055/s-2007-990883,2007-12-01,0.6273077510054852
Angewandte Chemie International Edition,Total Synthesis of (±)‐Alopecuridine and Its Biomimetic Transformation into (±)‐Sieboldine A,"The features you need: The first total synthesis of lycopodium alkaloid alopecuridine has been achieved in 13 steps in the longest linear sequence, and its biomimetic conversion into sieboldine A has been validated through a two-step oxidation. The synthesis features a semipinacol rearrangement of a functionalized medium-sized ring and an intramolecular pinacol coupling mediated by SmI2 (see scheme; Boc=tert-butoxycarbonyl).",10.1002/anie.201008147,2011-03-22,0.6273065562893123
Journal of Organic Chemistry,"Convergent Approach to Pumiliotoxin Alkaloids. Asymmetric Total Synthesis of (+)-Pumiliotoxins A, B, and 225F","A versatile convergent approach for preparing the pumiliotoxin alkaloids has been developed employing Pd(0)-catalyzed cross-coupling reactions between homoallylic organozincs and vinyl iodides. The (Z)-iodoalkylidene indolizidine 34, which served as a common key intermediate, was synthesized through highly stereoselective addition of the chiral silylallene 19 to (S)-acetylpyrrolidine followed by a palladium-catalyzed intramolecular carbonylation[bond]cyclization sequence. This synthetic process allowed the first total synthesis of (+)-pumiliotoxin 225F. The intermediate (Z)-iodoalkylidene indolizidine 34 obtained was converted to a homoallylzinc chloride derivative and subjected to homoallyl-vinyl cross-coupling with the (E)-vinyl iodide 42 using Pd(PPh(3))(4) catalyst to give the cross-coupled product 47 with a 1,5-diene side chain. Subsequent deprotection provided (+)-pumiliotoxin A. On the other hand, the (Z)-iodoalkylidene indolizidine 34 was transformed into the homoallyl-tert-butyl zinc derivative, which underwent palladium-catalyzed cross-coupling with the (E)-vinyl iodide 50 and subsequent deprotection to afford (+)-pumiliotoxin B.",10.1021/jo0200466,2002-06-28,0.6273042312003078
European Journal of Organic Chemistry,Enantioselective Approach to the Right‐Hand Substructure of Solanoeclepin A,"An enantioselective synthesis of the right‐hand substructure of solanoeclepin A has been developed. The key step was an intramolecular [2+2] photocycloaddition between an allene and a butenolide providing a methylenecyclobutane with three quaternary carbon atoms in a complex tetracyclic framework. Other crucial steps included an enantioselective Noyori transfer hydrogenation of a ketone, a diastereoselective silver‐mediated silyl dienolate allylation, and a diastereoselective cyclopropanation of an allylic alcohol. The installation of the bridgehead methyl group by reduction of the lactone moiety proved to be troublesome.",10.1002/ejoc.201601094,2016-10-26,0.6273031000053159
Journal of Organic Chemistry,"Diastereoselective Hydroxylation of 6-Substituted Piperidin-2-ones. An Efficient Synthesis of (2<i>S</i>,5<i>R</i>)-5-Hydroxylysine and Related α-Amino Acids","The synthesis of (2S,5R)-5-hydroxy-6-oxo-1,2-piperidinedicarboxylates (5) and related (3S,6R)-3-hydroxy-6-alkyl-2-oxo-1-piperidinecarboxylates has been developed. The approach is based on the asymmetric hydroxylation of enolates generated from the corresponding N-protected-6-substituted piperidin-2-ones. The utility of 5a as a precursor in the synthesis of (2S,5R)-5-hydroxylysine (1), an amino acid unique to collagen and collagen-like proteins, has also been demonstrated. (2S)-6-oxo-1,2-piperidinedicarboxylates (6) required for hydroxylation studies were prepared in 38-74% yield, starting from conveniently protected aspartic acid as inexpensive chiral adduct. Hydroxylation of 6 to 5 proceeds in high yield and excellent diastereoselectivity by treatment of their Li-enolate with (+)-camphorsulfonyloxaziridine at -78 degrees C. Ring opening of di-tert-butyl (2S,5R)-6-oxo-1,2-piperidinedicarboxylate ((5R)-5a) under reductive conditions afforded the corresponding 1,2-diol (17) in 91%, which was further transformed to (2S,5R)-5-hydroxylysine in four steps (84%). 17 is also a versatile intermediate in the preparation of tert-butyl (2S,5R)-2-[(tert-butoxycarbonyl)amino]-5-hydroxy-6-iodohexanoate (3) and tert-butyl (2S)-2-[(tert-butoxycarbonyl)amino]-4-[(2R)-oxiranyl]butanoate (4), two amino acid derivatives used in the total synthesis of the bone collagen cross-link (+)-pyridinoline (2a).",10.1021/jo025950c,2002-11-01,0.6272696953556517
Angewandte Chemie International Edition,Total Synthesis of Mycalolides A and B through Olefin Metathesis,An asymmetric total synthesis of the trisoxazole marine macrolides mycalolides A and B is described. This synthesis involves the convergent assembly of highly functionalized C1-C19 trisoxazole and C20-C35 side-chain segments through the use of olefin metathesis and esterification as well as Julia-Kocienski olefination and enamide formation as key steps.,10.1002/anie.201507795,2015-10-09,0.6272649524925042
Organic Letters,An Asymmetric Synthesis of (+)-Isostrychnine Based on Catalytic Asymmetric Tandem Double Michael Addition,"Herein, a concise asymmetric synthesis of (+)-isostrychnine is achieved in nine longest-linear steps with a 16% overall yield. The key features of this synthesis include the catalytic asymmetric tandem double Michael addition of a tryptamine-derived oxindole to an alkynone to facilely forge the A/B/C ring framework, a one-pot intramolecular dehydrative condensation/lactamization reaction to efficiently establish the E/G ring system, and an allylic diazene rearrangement to introduce the pivotal olefin for the subsequent intramolecular Heck reaction.",10.1021/acs.orglett.1c01828,2021-07-02,0.6272562488976245
Journal of Organic Chemistry,Synthesis and Cytotoxicity of Amino-<i>s</i><i>eco</i>-DSA:  An Amino Analogue of the DNA Alkylating Agent Duocarmycin SA,"This paper describes the synthesis of methyl 5-amino-1-(chloromethyl)-3-[(5,6,7-trimethoxyindol-2-yl)carbonyl]-1,2-dihydro-3 H -pyrrolo[3,2- e ]indole-7-carboxylate 8, an amino analogue of the anticancer antibiotic and potent DNA minor groove alkylating agent seco -duocarmycin SA. Key points in the synthesis are sequential radical cyclization and Hemetsberger reaction steps to construct the indoline and indole rings of the target compound from a 1,2,3-trisubstituted benzene precursor. An intermediate has been resolved by chiral chromatography to provide the separate enantiomers of 8 . Racemic 8 alkylates DNA at adenine in AT rich sequences, similar to seco -duocarmycin SA and the previously reported amino- seco -CBI 7, but is 15−60 times less potent than 7 in an in vitro cytotoxicity test. Derivatives of 8 in which the amino group is replaced by an electron-withdrawing nitro or nitrobenzylcarbamate substituent are considerably less toxic and may have application as prodrugs to be activated selectively in a tumor environment.",10.1021/jo990464j,1999-07-16,0.6272411009652962
Organic Process Research & Development,Synthetic Route Discovery and Introductory Optimization of a Novel Process to Idebenone,"An environmentally benign, convenient, high yielding, and cost-effective synthesis leading to idebenone is disclosed. The synthesis includes a bromination process for the preparation of 2-bromo-3,4,5-trimethoxy-1-methylbenzene, a protocol for the Heck cross-coupling reaction using either thermal or microwave heating, olefin reduction by palladium catalyzed hydrogenation, and a green oxidation protocol with hydrogen peroxide as oxidant to achieve the benzoquinone framework. The total synthesis is composed of six steps that provide an overall yield of 20% that corresponds to a step yield of 76%.",10.1021/op200051v,2011-03-21,0.6272399223873197
Tetrahedron,A practical synthesis of a key intermediate for the production of β-lactam antibiotics,,10.1016/s0040-4039(98)01700-6,1998-10-01,0.6272366197043687
Journal of Organic Chemistry,Tuning the Acceptors in Catalyzed Cyclizations Initiated by Allenes. Silylstannylation/Cyclization of Allene-Aldehydes for Synthesis of Polyalkylated Indolizidines Including 223A Congeners,"Starting from succinamide and 1,2-heptadiene-4-ol, a racemic allene-aldehyde substrate, 20, suitable for R(3)SiSnR'(3)-mediated cyclization was synthesized in six steps and in 21% yield. Stereoselective cyclization (relative cis configuration at the new stereogenic centers of the homoallyl alcohol generated) proceeded smoothly, giving a mixture of indolizidinols bearing five contiguous stereocenters in a combined yield of 80%. Relative configurations of each of the products were unequivocally established by a combination of 2D NMR experiments and single-crystal X-ray analysis. The major indolizidinol obtained in 32% yield was elaborated into indolizidine 5,8-epi-indolizidine 223A via a five-step reaction sequence in 32% overall yield. The second major component (24%) of the key cyclization yielded, in four steps, indolizidine 6,8-epi-223 in 14% yield. Even though revision of the initially postulated structure foiled our original synthetic plans for the natural product, indolizidine 223A, the new stereoselective cyclization strategy and several selective transformations of the indolizidine derivatives reported here may find further applications for the synthesis of highly alkylated indolizidine and other related alkaloids.",10.1021/jo048580w,2004-11-20,0.6272163712733265
Tetrahedron,New cytochalasins: Synthetic studies of a novel HIV-1 protease inhibitor,,10.1016/0040-4039(96)00778-2,1996-06-01,0.6272129916749811
Journal of Organic Chemistry,Scalable Asymmetric Syntheses of Foslevodopa and Foscarbidopa Drug Substances for the Treatment of Parkinson’s Disease,"Foslevodopa (FLD, levodopa 4′-monophosphate, 3 ) and foscarbidopa (FCD, carbidopa 4′-monophosphate, 4 ) were identified as water-soluble prodrugs of levodopa (LD, 1 ) and carbidopa (CD, 2 ), respectively, which are useful for the treatment of Parkinson’s disease. Herein, we describe asymmetric syntheses of FLD ( 3 ) and FCD ( 4 ) drug substances and their manufacture at pilot scale. The synthesis of FLD ( 3 ) employs a Horner–Wadsworth–Emmons olefination reaction followed by enantioselective hydrogenation of the double bond as key steps to introduce the α-amino acid moiety with the desired stereochemistry. The synthesis of FCD ( 4 ) features a Mizoroki–Heck reaction followed by enantioselective hydrazination to install the quaternary chiral center bearing a hydrazine moiety.",10.1021/acs.joc.1c00905,2021-07-19,0.6272073983074943
Synthesis,Diastereoselective Synthesis of (<i>S</i>)- and (<i>R</i>)-α-Phenylserine by a Sulfinimine-Mediated Strecker Reaction,"A straightforward and efficient diastereoselective synthesis of (S)- and (R)-α-phenylserine is reported. The key step involves an asymmetric Strecker reaction of a chiral N-sulfinyl ketimine, which was obtained from the commercially available 2-hydroxyacetophenone.",10.1055/s-2004-837308,2004-12-22,0.6271943417652329
Synthesis,"General Synthetic Approach to Rotenoids via Stereospecific, Group-Selective 1,2-Rearrangement and Dual SNAr Cyclizations of Aryl Fluorides","A general synthetic approach to rotenoids is described, featuring 1) stereospecific, group-selective 1,2-rearrangements of epoxy alcohols, and 2) SNAr oxy-cyclizations of aryl fluorides. The common intermediate epoxyketone, en route to (–)-rotenone and (–)-deguelin, was prepared from d-araboascorbic acid in five steps. Also described is the conversion of (–)-deguelin into oxidized congeners, (–)-tephrosin and (+)-12a-epi-tephrosin.",10.1055/s-0037-1611654,2019-01-23,0.6271789205096735
Synlett,A Regioselective Route to 5- and 6-Azaindoles,International audience,10.1055/s-2005-871946,2005-01-01,0.6271765649752492
Synthesis,A Short Route to (±)-<i>N</i>-Hydroxylysine and (±)-Laminine by Palladium-Catalyzed Reactions,"All articles of this category The title compounds were conveniently synthesized by efficient sequential one-pot amination-alkylation starting from ( Z )-4-acetoxy-2-butenyl ethyl carbonate ( 3 ) with tert -butyl ( tert -butoxycarbonyloxy)carbamate, dimethylamine and methyl (diphenylmethyleneamino) acetate. Hydrogenation and hydrolysis of the 1,4-adducts afforded N 6 -hydroxylysine [2-amino-6-(hydroxyamino)hexanoic acid, 1 ) and laminine hydrochloride [2-amino-6-(trimethylammonio)hexanoic acid chloride, 2 ] in 65 % and 39 % yield, respectively.",10.1055/s-1993-25858,1993-01-01,0.627176060299971
Journal of Organic Chemistry,Total Synthesis of (−)-Stemoamide,"A stereocontrolled total synthesis of (-)-stemoamide (1) is presented. The synthesis starts from commercially available (S)-pyroglutaminol (4). A chemoselective iodoboration of 5 was used to access key intermediate 3. The beta,gamma-unsaturated azepine derivative 2 was obtained via a Pd(0)-catalyzed sp(2)-sp(3) Negishi cross-coupling using a Reformatsky nucleophile followed by a ring-closing metathesis reaction. The required C8-C9 trans-stereochemistry of 1 was accessed through a stereoselective bromolactonization/1,4-reduction sequence.",10.1021/jo070498o,2007-04-24,0.6271683258668407
Tetrahedron,Synthesis of novel 5-amino-1-aroylpyrazoles,,10.1016/j.tetlet.2008.07.166,2008-08-04,0.6271679263948721
Tetrahedron,A novel synthesis of 2-amino- and 2-hydroxycarbazoles,,10.1016/s0040-4039(01)95137-8,1978-01-01,0.6271679263948721
Angewandte Chemie International Edition,Total Synthesis of Glycocinnasperimicin D,"A three-fragment coupling strategy afforded the antibiotic glycocinnasperimicin D (1). The convergent total synthesis features a Heck reaction to form the cinnamoyl glycoside, the [3,3] sigmatropic rearrangement of an allyl cyanate for the stereoselective synthesis of the allyl amine, and the coupling of a glycosyl isocyanate with an amino sugar for the construction of the urea glycoside linkage.",10.1002/anie.200500892,2005-06-14,0.6271632422479002
Tetrahedron,Improved procedure for the enantioselective synthesis of dihydrooxazolo and dihydrothiazolo ring-fused 2-pyridones,,10.1016/j.tetlet.2010.02.162,2010-03-04,0.6271578941007695
Tetrahedron,Stereoselective synthesis of the tricyclic core of manzamine a: The bradsher cycloaddition route,,10.1016/0040-4039(95)02071-3,1995-12-01,0.6271523751868452
Journal of Organic Chemistry,Stereocontrolled Syntheses of Carbocyclic <i>C-</i>Nucleosides and Related Compounds,"Carbocyclic 9-deazapurine nucleosides (1-4), a spiranic pyrimidone carbocyclic compound (5), and an unusual carbocyclic isonucleoside (6) were prepared as enantiomerically pure compounds via the key intermediates 10 and 21 from 1,4-gamma-ribonolactone. The key intermediate 10 was prepared by stereoselective reduction with Bu3SnH and then converted to carbocyclic C-ribonucleosides 1, 3, and 4. 2',3'-Didehydro-2',3'-dideoxycarbocyclic 9-deazainosine (2) was prepared from a 2',3'-dimesylate 17 by treatment with Li2Te followed by an acidic deprotection. The key bicyclic intermediate 21 was prepared from a diol 20 by an intramolecular cyclization using CHI3-Ph3P-imidazole and converted to the spiranic compound 5 and an olefinic nucleoside 6 by the construction of the heterocyclic moiety followed by deprotection.",10.1021/jo010224f,2001-06-14,0.6271518281921133
Tetrahedron,First total synthesis of (+)-cassiol. A potent antiulcerogenic compound,,10.1016/s0040-4039(01)80292-6,1989-01-01,0.6271475848215046
Organic Process Research & Development,Development of a Green and Sustainable Manufacturing Process for Gefapixant Citrate (MK-7264) Part 2: Development of a Robust Process for Phenol Synthesis,"Various synthetic routes to 2-isopropyl-4-methoxyphenol 3, the phenol core of Gefapixant citrate (MK-7264), are described, which provide better alternatives to the initial four-step supply route. These new routes include a coumarin fragmentation approach in flow, a rhenium-catalyzed isopropylation of mequinol, and a bromination/methoxylation of 2-isopropylphenol. After exploring several approaches, a robust two-step process for the preparation of 3 from the commodity starting material 2-isopropylphenol was developed. The optimized route employs a highly regioselective bromination. After isolating the bromophenol DABCO cocrystal, a copper-catalyzed methoxylation delivers 3 in high yield. This route is successfully demonstrated at the plant scale with low process mass intensity and cost.",10.1021/acs.oprd.0c00241,2020-10-16,0.6271428640515783
Journal of Organic Chemistry,"Highly Diastereoselective Route to α-Glucosidase Inhibitors, Neosalacinol and Neoponkoranol","A facile and highly diastereoselective route to potent natural α-glucosidase inhibitors, i.e., neosalacinol (4) and neoponkoranol (6), isolated from the traditional Ayurvedic medicine ""Salacia"" was developed by intramolecular cyclization of appropriately substituted sulfides (9 and 12).",10.1021/acs.joc.5b02894,2016-03-25,0.6271279411585395
Angewandte Chemie International Edition,Synthesis of Cyclopamine Using a Biomimetic and Diastereoselective Approach,"From Homer to hedgehog: Cyclopamine, the first inhibitor of the hedgehog signaling pathway, causes cyclopia in embryos but in adults it is a potent anticancer drug. A concise biomimetic and diastereoselective synthesis of cyclopamine (2) starting from commercially available dehydroepiandrosterone (1) now also provides access to several analogues.",10.1002/anie.200902520,2009-07-10,0.6271228313324423
Organic Letters,Enantioselective Total Synthesis of (−)-Misramine,"The enantioselective total synthesis of an unusual pentacyclic proaporphine alkaloid, (-)-misramine, was achieved. The synthetic strategy relied on an enantioselective intramolecular Friedel-Crafts-type 1,4-addition using an asymmetric organocatalyst to construct a spiroindane skeleton containing an all-carbon quaternary stereocenter and a double reductive amination of the keto-aldehyde to form a piperidine ring toward the end of the synthesis. This work is the first example of asymmetric synthesis of a proaporphine alkaloid.",10.1021/acs.orglett.8b02198,2018-08-06,0.6271134731930805
Journal of Organic Chemistry,Synthesis of 4-Substituted-3-aminopiperidin-2-ones:  Application to the Synthesis of a Conformationally Constrained Tetrapeptide<i>N</i>-Acetyl-Ser-Asp-Lys-Pro,"A new and practical synthetic strategy is developed for the synthesis of six-membered lactam-bridged dipeptides, 4-substituted-3-aminopiperidin-2-ones, featuring two key steps: (a) a diastereoselective addition of cuprate to (E)-alpha,beta-unsaturated ester (3) and (b) racemization-free reductive amination. On the basis of this methodology, conformationally constrained tetrapeptide N-acetyl-Ser-Asp-Lys-Pro (AcSDKP) (2) has been successfully synthesized from 3-amino-4-vinylpiperidin-2-one (22).",10.1021/jo050736k,2005-06-22,0.627065055375383
Organic Process Research & Development,Scalable Syntheses of the Vaulted Biaryl Ligands VAPOL and VANOL via the Cycloaddition/Electrocyclization Cascade,"Synthetic approaches to the VANOL and VAPOL ligands are developed which are straightforward, inexpensive, efficient, and amenable to large-scale preparation of the ligands since minimum chromatographic purification is required. The key step in each synthesis is a cycloaddition/electrocyclic ring-opening/electrocyclic ring closure/tautomerization cascade that provides a direct one-step route to the monomers from which each ligand is prepared. Improved phenol coupling protocols are developed which provide the racemic ligands. Finally, dramatic improvements in the resolution procedures feature the reduction of the number of chemical steps and the defining of new crystallization protocols that greatly enhance the ease and reliability of the separation of diastereomeric salts.",10.1021/op200088b,2011-07-12,0.6270586839317237
Journal of the American Chemical Society,"Total Synthesis and Structural Revision of TMG-chitotriomycin, a Specific Inhibitor of Insect and Fungal β-<i>N</i>-Acetylglucosaminidases","TMG-chitotriomycin, a potent and selective inhibitor of the beta-N-acetylglucosaminidases that possesses an unique N,N,N-trimethyl-d-glucosamine (TMG) residue, is revised to be the TMG-beta-(1-->4)-chitotriose instead of the originally proposed alpha-anomer via its total synthesis, for which a highly convergent approach was developed in which the sterically demanding (1-->4)-glycosidic linkages are efficiently constructed by the Au(I)-catalyzed glycosylation protocol with glycosyl o-hexynylbenzoates as donors.",10.1021/ja9055245,2009-08-07,0.6270493695330094
Synlett,A New Process for the Total Synthesis of Sparstolonin B,"A novel and simple route was developed that gives sparstolonin B in high yields from affordable commercial compounds. A Diels–Alder strategy was used for the facile construction of the multisubstituted diphenyl ether. The xanthenone segment was obtained by cyclization in an intramolecular Friedel–Crafts reaction, followed by selective reduction of a ketone group and a transformation from a hydroxy group into a cyano group. The final part of the lactone was directly derived by the reduction of the cyano group with Raney nickel.",10.1055/s-0036-1588723,2017-02-23,0.6270478697299067
Organic Letters,"One-Pot, High-Yielding, Oxidative Cyclodehydrogenation Route for N-Doped Nanographene Synthesis","An intramolecular oxidative cyclodehydrogenation via a one-pot process is described, which induces selective C-C bond formation and bromine functionalization. The application of this new route gives rise to a novel family of partially fused, selectively brominated N-doped pyrimidine graphenes.",10.1021/acs.orglett.5b03312,2015-12-18,0.6270403347887086
Organic Process Research & Development,A Formal Synthesis of (+)-Discodermolide,"Herein, we report the formal synthesis of (+)-discodermolide ( 1 ), a promising anticancer agent of sponge origin, in 24 linear steps, with 35 steps in total. The route proceeds from lactone 2, a building block containing the common 1,2- anti -2,3 -syn stereotriad found in each of the three subunits, methyl ketone 4 (C 1 −C 6 ), vinyl iodide 7 (C 9 −C 14 ), and iodide 8 (C 15 −C 24 ) utilized for the construction of 1 . The key fragment union was achieved by a Suzuki cross-coupling between 7 and 8 .",10.1021/op049807s,2005-03-16,0.627025295583903
Organic Process Research & Development,Process Research and Scale-Up for a β-3 Adrenergic Receptor Agonist,"A scaleable synthesis of the β-3 adrenergic receptor agonist, (4-{2-[2-(6-aminopyridin-3-yl)-(2 R )-hydroxy-ethylamino]ethoxy}phenyl)acetic acid is presented. The key coupling step utilizes a silyl-protected β-hydroxy tosylate to alkylate a primary amine, thus avoiding water-soluble intermediates and reducing unwanted side products. Deprotection strategies and isolation of a zwitterionic species are described.",10.1021/op049969o,2004-05-28,0.6269953171887018
Organic Letters,Total Synthesis of Paralemnolide A,"The first total synthesis of tricyclic bisnorsesquiterpene paralemnolide A, isolated from the soft coral Paralemnalia thyrsoides, was achieved. This synthesis features the lactonization of the cyclohexene derivative having a tert-butyl ester via stereoselective epoxidation followed by treatment with a Brønsted acid and construction of the novel tricyclic skeleton by an intramolecular Reformatsky-Honda reaction.",10.1021/acs.orglett.7b03038,2017-10-17,0.6269928363708065
Journal of Organic Chemistry,Synthesis of Kaempferitrin,"A short synthesis of Kaempferitrin (1), a 3,7-diglycosylflavone, is reported. Key features include the synthesis of a protected form of kaempferol in which all four hydroxy groups are differentiated and the first bis-glycosylation of a dihydroxyflavone. This synthesis will allow the preparation of derivatives for further explorations into the origins of this compound's biological activity.",10.1021/jo070502w,2007-05-11,0.6269677812743707
Journal of Organic Chemistry,"Enantioselective Construction of <i>Cis</i>-2,6-Disubstituted Dihydropyrans: Total Synthesis of (−)-Centrolobine","This paper presents a simple and efficient route to chiral cis-6-substituted 2-(2-hydroxyethyl)-5,6-dihydro-2H-pyrans, a versatile chiral building block. The strategy is based on three key transformations: enantioselective hetero-Diels-Alder (HDA) reaction of aldehyde with Danishefsky's diene, selective reduction of carbonyl function, and Claisen or related rearrangement. The synthetic utility of the methodology is illustrated by total synthesis of antibiotic (-)-centolobine.",10.1021/jo902167r,2010-01-29,0.6269582336045721
Organic Process Research & Development,Amalgamation of Synthetic Biology and Chemistry for High-Throughput Nonconventional Synthesis of the Antimalarial Drug Artemisinin,"The development of a cost-effective process for the production of artemisinin, the precursor of all artemisinin-derived drugs, the first-line treatment for malaria, has been a long-pursued endeavor. The breakthrough achievement of coaxing genetically engineered yeast to express Artemisia annua genes for the commercial production of artemisinic acid, an advanced intermediate in the synthesis of artemisinin, has yet to fully realize an affordable malaria treatment for the poor because of the lack of a cost-effective chemical conversion into artemisinin. We describe herein a commercially feasible and pragmatic synthesis of artemisinin from amorpha-4,11-diene, an early-stage intermediate produced in 2-fold higher molar yield than engineered yeast cells can process into artemisinic acid. The key to this novel approach is an exceedingly effective functionalization of the isopropenyl group of amorphadiene via endo -epoxyamorphadiene to give dihydroartemisinic acid, which upon esterification followed by oxidation and cyclicization furnishes pure artemisinin in approximately 60% yield.",10.1021/acs.oprd.6b00414,2017-02-27,0.6269577800903847
Journal of Organic Chemistry,Synthesis of (±)-<i>epi</i>-Stegobinone Utilizing Silacyclopropanes as Synthetic Intermediates,The synthesis of (+/-)-1'-epi-stegobinone has been accomplished in ten steps and 17% overall yield from a recently reported silacyclopropane-derived diol. All stereocenters of the final product were established relative to the stereochemistry of the initial silacyclopropane. This synthesis represents the first time silacyclopropane reactivity has been employed in a target-directed synthesis.,10.1021/jo0620011,2006-12-29,0.6269532303972657
Journal of Organic Chemistry,"Synthesis of 1,4-Annulated Cyclooctatetraenophanes Based on a Novel Cubane Building Block Approach","A general synthetic approach to strained 1,4-annulated cyclooctatetraene-based cyclophanes is described. A key feature in this approach is exploitation of the cubane core as a masked cyclooctatetraene synthon. Thus, 1,4-disubstituted cubanes 3 and 4 used as precursors to cyclooctatetraenophanes have been prepared in four steps from the readily available 1,4-cubanedicarboxaldehyde (5). The synthesis of 3 was effected by palladium/copper-mediated coupling of 1,4-bis[(Z,Z)-2-iodovinyl]cubane (6) and 1,4-bis[(Z,Z)-but-1-en-3-ynyl]cubane (8). For the synthesis of 4, on the other hand, modified Eglington-Glaser coupling was applied for the macrocyclization step. The general characteristic of Rh(I) to induce [2 + 2] cycloreversion of the cubane core to syn-tricyclo[4.2.0.0(2,5)]octa-3,7-diene followed by thermal rearrangement to cyclooctatetraene was applied as a key structural transformation toward targeted cyclooctatetraenophanes 1 and 2.",10.1021/jo049643d,2004-07-13,0.6269517388689351
Journal of Organic Chemistry,Enantiospecific Syntheses of Valienamine and 2-<i>e</i><i>pi</i>-Valienamine<sup>1</sup>,"Cyclic sulfite 10, readily available from (-)-quinic acid (3) in 10 steps, was ring opened regio- and stereospecifically with azide anion to give (1S,2R,3R,4R)-1-azido-3,4-di-O-benzyl-5-(benzyloxymethyl)cyclohex-5-ene-2,3,4-triol (11). Deprotection of 11 afforded, for the first time, 2-epi-valienamine (2), which was isolated as penta-N,O-acetyl-2-epi-valienamine (14). The configuration of the free hydroxy group in 11 was inverted by a two-step sequence to give the blocked valienamine 19 that was deprotected to give valienamine (1), isolated as penta-N,O-acetylvalienamine (21). This approach furnished (+)-valienamine (1) in 16 steps (7% overall yield) and recorded the first synthesis of 2-epi-valienamine (2) in 13 steps (11% overall yield).",10.1021/jo982024i,1999-02-24,0.6269466539127166
European Journal of Organic Chemistry,A Carbohydrate‐Based Synthesis of the C13–C22 Fragment of Amphidinolide X,"Abstract A facile carbohydrate‐based route was developed for the synthesis of the tetrahydrofuran (C13–C22) fragment of amphidinolide X. Starting from L ‐sorbose, the key reactions followed include the stereoselective synthesis of a quaternary center at C1, Barton–McCombie deoxygenation at C2, Mitsunobu inversion at C3, and chain elongation by a Wittig reaction at C5.",10.1002/ejoc.201101605,2012-02-06,0.6269465112198133
Tetrahedron,"Dysidotronic acid, a new and selective human phospholipase A2 inhibitor from the sponge Dysidea sp.",,10.1016/s0040-4039(00)00362-2,2000-04-01,0.6269465038989459
Organic Letters,Enantioselective Total Synthesis of (+)-Sieboldine A and Analogues Thereof,"An 11-step enantioselective total synthesis of (+)-sieboldine A ( 1 ) has been accomplished from (5 R )-methylcyclohex-2-en-1-one ( 16 ), in which an intramolecular ketone/ester reductive coupling followed by one-pot acidic treatment to quickly construct the unique oxa-spiroacetal and a TsOH-catalyzed displacement to directly form the characteristic N -hydroxyazacyclononane ring successfully served as the key methodologies. Moreover, several full-skeleton analogues of 1 were also synthesized on the basis of the advanced intermediates, and their inhibitory effects on electric eel acetylcholinesterase were examined.",10.1021/acs.orglett.2c02737,2022-10-10,0.6269419438297736
Angewandte Chemie International Edition,Enantioselective Total Synthesis of Fortimicin B,"Fortimicins, featuring a pseudodisaccharide scaffold, are an unusual class of aminoglycosides (AGs) with potent efficacy against several aminoglycoside-resistant bacterial strains. Notably, these molecules also exhibit lower inherent ototoxicity and nephrotoxicity than common aminoglycosides. Consequently, fortimicins are a promising type of protoypical molecules for the development of the next generation of aminoglycoside antibiotics. Here, we report the asymmetric total synthesis of fortimicin B in 12 steps (longest linear sequence, LLS) from readily available starting materials. An enantioselective Cu(II)-catalyzed inverse-electron-demand Diels-Alder (IEDDA) reaction of 2-pyrones and N-substituted 2-oxazolones was developed for the efficient synthesis of the fortamine fragment, which previously required a lengthy multistep synthesis owing to its complex stereochemistry. The 6-epi-purpurosamine B fragment was efficiently synthesized through a Cr(II)/Co(I)-mediated C─C bond coupling between aldehydes and alkyl halides. Within these two fragments, the stereoselective construction of the α-glycosidic bond of fortimicin B was realized via the gold(I)-catalyzed glycosylation. Overall, this study provides an efficient synthetic platform for future investigations into the structure-activity relationships of fortimicins.",10.1002/anie.202424235,2025-03-13,0.6269143041066222
Journal of the American Chemical Society,"Convergent, Enantioselective Syntheses of Guanacastepenes A and E Featuring a Selective Cyclobutane Fragmentation<sup>1</sup>","The evolution of a convergent strategy that led to efficient, enantioselective syntheses of both natural (+)- and unnatural (-)-guanacastepene E and formal total syntheses of (+)- and (-)-guanacastepene A is described. A union of five- and six-membered ring intermediates by an efficient pi-allyl Stille cross-coupling reaction was followed by an intramolecular enone-olefin [2 + 2] photocycloaddition and a stereoelectronically controlled, reductive fragmentation of the resulting cyclobutyl ketone. The latter two transformations enabled controlled formation of the C-11 quaternary stereocenter and the central seven-membered ring of the guanacastepenes. An enantiospecific synthesis of the functionalized five-membered ring vinyl stannane from the monoterpene R-(-)-carvone featuring a carbon-carbon bond forming ring contraction was also developed.",10.1021/ja060847g,2006-05-01,0.626904307204437
Synlett,Practical and Scalable Total Syntheses of (+)-Dysidavarones A–C,"Abstract A practical and scalable enantioselective total syntheses of the marine anticancer sesquiterpene quinone meroterpenoids (+)-dysidavarones A–C has been accomplished. The central bridged bicyclo[3.3.1]nonane structure of dysidavarones was efficiently established by a one-pot intermolecular diastereoselective alkylation and intramolecular α-arylation of a Wieland–Miescher ketone derivative with a substituted benzylic bromide, without protection of the more-reactive C(4) carbonyl group. (+)-Dysidavarones A and ‘E’ were prepared on a 150-mg scale, demonstrating the efficiency and reliability of our synthetic route and providing sufficient amounts of the dysidavarones for further bioactivity evaluation.",10.1055/a-2066-0860,2023-03-30,0.6268910945768942
Angewandte Chemie International Edition,"Total Synthesis of Echinoside A, a Representative Triterpene Glycoside of Sea Cucumbers","Echinoside A, a sulfonylated holostane tetrasaccharide with potent anticancer and antifungal activity, was synthesized in a longest linear sequence of 35 steps and 0.6 % overall yield. The synthetic approach is adaptable to the synthesis of congeners and analogues, as exemplified by the ready synthesis of ds-echinoside A and echinoside B, and thus will facilitate in-depth studies on the promising biological effects of echinoside A. Moreover, the present synthesis demonstrates the feasibility of synthetic access to the characteristic complex triterpene glycosides that occur ubiquitously in sea cucumbers.",10.1002/anie.201703610,2017-05-08,0.6268906806562876
Journal of Organic Chemistry,Total Synthesis of Lathyranoic Acid A,"The first total synthesis of lathyranoic acid A (1) was accomplished stereoselectively in a linear sequence of 20 steps and an overall yield of 1.4%. This modular synthesis featured a cyclic, stereocontrolled Cu-catalyzed intramolecular cyclopropanation to construct the cis-cyclopropane unit, a Grubbs metathesis to construct the γ-substituted cyclopentenone moiety, and an anion-mediated conjugate addition.",10.1021/jo102033h,2011-01-28,0.6268770585777825
Organic Letters,A Concise Route to Dihydrobenzo[<i>b</i>]furans: Formal Total Synthesis of (+)-Lithospermic Acid,"A sequence of Sonogashira coupling, Pd(II)-catalyzed carbonylative annulation, and benzofuran reduction (Mg, MeOH, NH(4)Cl) provides a convergent and modular synthetic route to trans-2-aryl-2,3-dihydrobenzo[b]furan-3-carboxylates, which are a structural feature of numerous biologically active natural products. This versatile strategy was applied to the formal total synthesis of the anti-HIV natural product (+)-lithospermic acid.",10.1021/ol201130h,2011-06-07,0.6268741916113484
Synlett,"Expeditious Synthesis of 4-(<i>tert</i>-Butylcarbonyl)-7α-methoxy-3-methyl-Δ<sup>3</sup>-cephem 1,1-Dioxide. Convenient Access to 7-Substituted Analogues","All articles of this category A practical and efficient route leading to the synthesis of 4-( tert -butylcarbonyl)-7α-methoxy-3-methyl-Δ 3 -cephem 1,1-dioxide ( 2 ), a key-intermediate in the preparation of potent inhibitors of mammalian serine proteinases, is reported. The new synthetic pathway has allowed easy access to an array of 7-substituted cephem derivatives. cephems - 1,1-dioxocephem tert -butyl ketones - 7-diazocephem - methoxylation - protease inhibitors",10.1055/s-1998-1621,1998-03-01,0.6268713042479767
Journal of Organic Chemistry,Chiral Iminoesters Derived from <scp>d</scp>-Glyceraldehyde in [3 + 2] Cycloaddition Reactions. Asymmetric Synthesis of a Key Intermediate in the Synthesis of Neuramidinase Inhibitors,Silver-catalyzed endo-selective and copper-catalyzed exo-selective asymmetric [3 + 2] cycloadditions of acrylates to chiral iminoesters derived from D-glyceraldehyde have been investigated. The reaction diastereoselectively provides highly functionalized pyrrolidines. This approach was used to develop the first asymmetric synthesis of a key intermediate in the synthesis of pyrrolidine influenza neuramidinase inhibitors.,10.1021/jo401967a,2013-10-21,0.6268658739661425
European Journal of Organic Chemistry,Enantioselective Synthesis of Daurichromenic Acid and Confluentin,Abstract The first asymmetric synthesis of daurichromenic acid and confluentin is described. The key step of the sequence leading to both natural products is a highly enantioselectivedomino aldol/oxa Michael reaction (97 % ee ) of farnesal and 2‐methoxy‐4‐methylsalicylaldehyde.,10.1002/ejoc.200901403,2010-01-07,0.6268633990330397
Organic Letters,"Asymmetric Synthesis of 4,4-Disubstituted-2-Imidazoli-dinones:  Potent NK<sub>1</sub> Antagonists","[structure: see text] A highly efficient and practical synthesis of 4,4-Disubstituted-2-Imidazolidinones utilizing a ""self-reproduction of the center of chirality"" strategy is described.",10.1021/ol030104p,2003-10-23,0.6268552145167656
Synlett,"Synthesis of Imidazolo[5,4-<i>b</i>]carbazole-4,10-quinones","The preparation of imidazolo[5,4-b]carbazole-4,10-quinones 9 is described. The key steps of the synthesis are selective halogen-metal exchanges on the imidazole 3 and subsequent addition to carbonyl groups of ethyl-3-formylindole-2-carboxylate 4.",10.1055/s-2004-822923,2004-01-01,0.6268510957840954
Organic Process Research & Development,Fit-for-Purpose Development of the Enabling Route to Crizotinib (PF-02341066),"A robust six-step process for the synthesis of crizotinib, a novel c-Met/ALK inhibitor currently in phase III clinical trials, has been developed and used to deliver over 100 kg of API. The process includes a Mitsunobu reaction, a chemoselective reduction of an arylnitro group, and a Suzuki coupling, all of which required optimization to ensure successful scale-up. Conducting the Mitsunobu reaction in toluene and then crystallizing the product from ethanol efficiently purged the reaction byproduct. A chemoselective arylnitro reduction and subsequent bromination reaction afforded the key intermediate 6 . A highly selective Suzuki reaction between 6 and pinacol boronate 8, followed by Boc deprotection, completed the synthesis of crizotinib 1 .",10.1021/op200131n,2011-06-30,0.6268478775703357
Angewandte Chemie International Edition,Nitrenoid from Oxime: A Practical Synthesis of Planar Chiral Ferrocenyl Phenanthridines via Nitrene‐Involved Ring‐Expansion Reaction,"Nitrenes and nitrenoids are highly reactive species and the proposed key intermediates in nitrogen-containing heterocyclic compound synthesis. In this work, we developed a practical method for the synthesis of phenanthridines by the reaction of oximes and Grignard reagents (with or without diethylzinc) via ring-expansion of magnesium coordinated nitrenoid complex as the key step. The method has been used to synthesize optically active planar chiral ferrocenyl phenanthridines.",10.1002/anie.202215530,2022-11-08,0.6268428587004877
Organic Letters,"Visible-Light-Promoted and Yb(OTf)<sub>3</sub>-Catalyzed Constructions of Coumarin-Pyrrole-(Iso)quinoline-Fused Pentacycles: Synthesis of Lamellarin Core, Lamellarin D Trimethyl Ether, and Lamellarin H","The efficient construction of a coumarin-pyrrole-isoquinoline-fused pentacycle via the visible-light-promoted cyclization of 4-(isoquinolin-1-ylmethyl)-3-nitrocoumarin or Yb(OTf)3-catalyzed coupling of 4-chloro-3-nitrocoumarin and 1-methylisoquinoline is reported. This methodology has further led to the development of the concise synthesis of the lamellarin core in one, two, and three steps, as well as of lamellarin D trimethyl ether in three steps.",10.1021/acs.orglett.5b03524,2016-01-07,0.6268251088722109
Tetrahedron,Expeditious and efficient synthesis of Strecker’s α-aminonitriles catalyzed by sulfated polyborate,,10.1016/j.tetlet.2017.04.058,2017-04-20,0.626824658080203
Tetrahedron,Sulfated polyborate-catalyzed efficient and expeditious synthesis of (un)symmetrical ureas and benzimidazolones,,10.1016/j.tetlet.2017.10.001,2017-10-04,0.626824658080203
Synthesis,(Z)-5-(4-Fluorophenyl)pent-4-enoic Acid: A Precursor for Convenient and Efficient Synthesis of the Antihypercholesterolemia Agent Ezetimibe,"A convenient and efficient total synthesis of ezetimibe, an intestinal cholesterol absorption inhibitor and useful anticholesteremic agent, is described. Based on (Z)-5-(4-fluorophenyl)pent-4-enoic acid as a starting compound, and taking the synthesis through further Z-configured intermediates, the total yield is remarkably increased, compared with the use of the corresponding E-configured starting substances or intermediates.",10.1055/s-0030-1258193,2010-08-05,0.6268200710262356
Organic Process Research & Development,"Development of a Pilot-Scale Preparation of <i>N</i>-[[(5S)-3-[4-(1,1-Dioxido-4- thiomorpholinyl)-3,5-difluorophenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide, PNU-288034, an Oxazolidinone Antibacterial Agent","As part of Pfizer's continuing efforts in the oxazolidinone area, we have developed an efficient synthesis of PNU-288034 and successfully implemented it on pilot scale. The key step was a novel, acid-catalyzed, double Michael addition of 2,6-difluoroaniline with divinyl sulfone to install the desired dioxidothiomorpholinyl ring. Regioselective nitration provided the desired para-nitrogen, which was converted to the penultimate carbamate using standard chemistry. The resulting carbamate proved to be an excellent substrate for the recently reported oxazolidinone synthesis. As is normally the case, removing impurities to achieve our quality targets for API was a challenge, but unexpectedly, some impurities also caused significant processing difficulties as well. In the end, a safe and robust process was developed which provided clinical-quality material in five linear steps with an overall yield of 41% and was proven reproducible in multiple pilot-plant campaigns.",10.1021/op050207i,2006-02-04,0.6267913288450876
Tetrahedron,A furan route to the asymmetric synthesis of trans-fused polyether building blocks,,10.1016/j.tetlet.2003.09.076,2003-10-15,0.6267892831981587
Organic Letters,Total Synthesis of the Lipid-Anchor-Attached Core Trisaccharides of Lipoteichoic Acids of <i>Streptococcus pneumoniae</i> and <i>Streptococcus oralis</i> Uo5,"Herein we report an efficient total synthesis of lipid-anchor-appended core trisaccharides of lipoteichoic acids of Streptococcus pneumoniae and Streptococcus oralis Uo5. The key features include the expedient synthesis of the rare sugar 2,4,6-trideoxy-2-acetamido-4-amino- d -Galp building block via one-pot sequential S N 2 reactions and the α-selective coupling of d -thioglucoside with the diacyl glycerol acceptor to construct a common disaccharide acceptor, which was utilized in the total synthesis of target molecules 1 and 2 .",10.1021/acs.orglett.9b04264,2019-12-30,0.6267704143670306
Synlett,A Facile Synthesis of 1-Substituted Cyclopropylsulfonamides,"A practical, convenient, and high-yielding three-step synthesis of cyclopropanesulfonamide and 1-substituted cyclopropanesulfonamides, starting from 3-chloropropanesulfonyl chloride, is described.",10.1055/s-2006-933130,2006-01-01,0.6267548362333653
Organic Process Research & Development,Research and Development of an Efficient Synthesis of a Key Building Block for Anti-AIDS Drugs by Diphenylprolinol-Catalyzed Enantio- and Diastereoselective Direct Cross Aldol Reaction,"High Resolution Image Download MS PowerPoint Slide An efficient method for synthesizing 1-({[(3 R,3 aS,6 aR )-hexahydrofuro[2,3- b ]furan-3-yloxy]carbonyl}oxy)pyrrolidine-2,5-dione ( 1 ), a key building block for HIV protease inhibitors, has been developed. A diphenylprolinol-catalyzed highly enantio- and diastereoselective cross aldol reaction of polymeric ethyl glyoxylate with an aldehyde was used as the key step. Acetalized aldol adduct was reduced with NaBH 4 to give the diol intermediate in quantitative yield. The acetal exchange reaction followed by hydrogenation with Pd/C catalyst afforded 1′ in 95% yield over 2 steps. The condensation of 1′ with a carbonate gave crystalline 1 (>99/1 dr, > 99% ee) after single crystallization. This is a highly practical synthetic method since environmentally benign organocatalysis is utilized, the amount of catalyst is reduced to 3 mol %, and all of the intermediates before 1′ can be used without any purification.",10.1021/acs.oprd.6b00178,2016-08-15,0.6267475027636623
Organic Process Research & Development,An Improved Synthetic Route to Drotaverine and Papaverine Using Substituted Nitrostyrenes as Key Intermediates,"An improved synthetic process for isoquinoline-based antispasmodic drugs (drotaverine and papaverine) has been developed that avoids the bulk use of metal cyanides traditionally employed in the preparation of arylacetonitrile intermediates. The industrial-scale synthesis of arylacetonitrile typically involves highly toxic metal cyanides, which pose significant safety and environmental hazards. The improved process replaces the low-yielding arylacetonitrile intermediate with a substituted nitrostyrene, thereby eliminating the need for metal cyanides on the industrial scale. Additionally, the implementation of in situ reactions at the n–1 and n–2 stages, coupled with an aqueous-phase reaction in the initial step, enhances sustainability both economically and environmentally. This approach results in 83% overall yields from substituted nitrostyrene 11 and 55.5% yield of nitrostyrene 11 from catechol 3, concise synthetic route, and reduced use of bulk solvents compared to the previously opted lengthy, lower-yielding routes through nitrile claiming 31% overall yield of nitrile 5 from catechol 3 and 56.5% overall yield from nitrile 5 to the active pharmaceutical ingredient.",10.1021/acs.oprd.5c00237,2025-10-24,0.6267470484880071
Tetrahedron,"New Regiospecific and stereoselective route to β-hydroxy selenides A (C,C) connective and stereospecific route to olefins and epoxides",,10.1016/s0040-4039(00)93887-5,1976-09-01,0.6267466685609233
Angewandte Chemie International Edition,A Facile Stereocontrolled Approach to CF<sub>3</sub>‐Substituted Triarylethenes: Synthesis of Panomifene,"The stereoselective preparation and Pd-catalyzed cross-coupling reaction of boronates 2 provides a new general and convenient route to CF3-substituted triaryl ethenes 3, in which the CF3 and Ar3 groups are cis to each other. The synthetic potential was demonstrated by the total synthesis of panomifene (Ar1=Ar3=Ph, Ar2=4-(OHCH2CH2NHCH2CH2O)-C6H4). Bpin=(pinacolato)boryl.",10.1002/anie.200353032,2004-02-02,0.6267371921959966
Synlett,"An Expedient Asymmetric Synthesis of N-Protected (S,S)-2-Aminomethyl-1-cyclopropanecarboxylic Acid",An enantioselective synthesis of a N-Boc-protected trans-cyclopropane γ-amino acid is reported. The key chiral aldehyde intermediate is prepared in enantiomerically pure form using a three-step aldol-cyclopropanation-retro-aldol protocol.,10.1055/s-0030-1258814,2010-10-08,0.6267349918265773
Synthesis,Studies on Macrocyclic Diterpenoids; Part 13: An Efficient Total Synthesis of (±)-Sarcophytol-M,"All articles of this category The total synthesis of (±)-sarcophytol-M, a marine cembranol, was achieved from ( E )-geraniol in twelve steps by using an intramolecular nucleophilic addition of a sulfur-stabilized carbanion to a ketone as the key step.",10.1055/s-1994-25601,1994-01-01,0.6267286585061611
Organic Process Research & Development,Research and Development on the Manufacturing Process of Dexmedetomidine from Chiral Precursors: Resolution–Racemization–Recycle Synthesis Strategy,"The present work describes the development of a new synthetic route to dexmedetomidine ( 1 ), widely used in hospital practice as a versatile anesthetic, free of respiratory distress effects. The conventional approach to the manufacture of compound 1 rests on the resolution of racemic medetomidine ( 2 ). However, besides a low recovery of the ( S )-enantiomer (∼0.2 kg from one kg of the racemate), the classical resolution suffers from production of chiral waste enriched in levomedetomidine ( R -enantiomer), which could not be racemized in a safe and practically applicable manner. We proposed a new precursor for dexmedetomidine, 2-(2,3-dimethylphenyl)propionic acid ( 5 ), to be resolved at preliminary steps instead of resolution of dexmedetomidine 1 itself. The resolved acid ( S )-enantiomer 4 is then used in the synthesis of 1 and the ( R )-enantiomer-enriched chiral waste are readily racemized in a simple, safe, and scalable manner and used again. Further synthesis steps involving ( S )-acid 4 included the preparation of sulfur ylide 19 from acid chloride 16 and dimethylsulfoxonium methylide 18, transformation of compound 19 into α-bromoketone 21, and its subsequent transformation to salts 25a – 25j . The “azide route” was found to be the optimum one for the preparation of aminoketone, providing the product with acceptable enantiomeric purity, and included the reaction of bromoketone 21 with sodium azide, followed by hydrogenation of the resulting azidoketone 30 . The Marckwald cyclization of aminoketone salts 25 with potassium thiocyanate afforded a dexmedetomidine thio derivative 26, the desulfurization of which gave the ( S )-enantiomer-enriched target product 1 in high yield. Excellent yields of the racemic acid 5 recycled after resolution and a high percentage recovery of the commercially available chiral amine 11 used for resolution, as well as preliminary enrichment of the crude product with the ( S )-enantiomer, allowed us to decrease the amount of chiral waste almost 4-fold compared to the classical resolution of racemic medetomidine ( 2 ). In addition, the exclusion of expensive Rh catalysts and chiral ligands, which are used in current methods, considerably decreased the manufacturing cost of 1 .",10.1021/acs.oprd.3c00388,2024-03-20,0.6267268710935872
Journal of the American Chemical Society,Development of Enantioselective Synthetic Routes to (−)-Kinamycin F and (−)-Lomaiviticin Aglycon,"The development of enantioselective synthetic routes to (-)-kinamycin F (9) and (-)-lomaiviticin aglycon (6) are described. The diazotetrahydrobenzo[b]fluorene (diazofluorene) functional group of the targets was prepared by fluoride-mediated coupling of a β-trimethylsilylmethyl-α,β-unsaturated ketone (38) with an oxidized naphthoquinone (19), palladium-catalyzed cyclization (39→37), and diazo transfer (37→53). The D-ring precursors 60 and 68 were prepared from m-cresol and 3-ethylphenol, respectively. Coupling of the β-trimethylsilylmethyl-α,β-unsaturated ketone 60 with the juglone derivative 61, cyclization, and diazo transfer provided the advanced diazofluorene 63, which was elaborated to (-)-kinamycin F (9) in three steps. The diazofluorene 87 was converted to the C(2)-symmetric lomaiviticin aglycon precursor 91 by enoxysilane formation and oxidative dimerization with manganese tris(hexafluoroacetylacetonate) (94, 26%). The stereochemical outcome in the coupling is attributed to the steric bias engendered by the mesityl acetal of 87 and contact ion pairing of the intermediates. The coupling product 91 was deprotected (tert-butylhydrogen peroxide, trifluoroacetic acid-dichloromethane) to form mixtures of the chain isomer of lomaiviticin aglycon 98 and the ring isomer 6. These mixtures converged on purification or standing to the ring isomer 6 (39-41% overall). The scope of the fluoride-mediated coupling process is delineated (nine products, average yield = 72%); a related enoxysilane quinonylation reaction is also described (10 products, average yield = 77%). We establish that dimeric diazofluorenes undergo hydrodediazotization 2-fold faster than related monomeric diazofluorenes. This enhanced reactivity may underlie the cytotoxic effects of (-)-lomaiviticin A (1). The simple diazofluorene 103 is a potent inhibitor of ovarian cancer stem cells (IC(50) = 500 nM).",10.1021/ja307497h,2012-10-03,0.6267234989825536
Tetrahedron,Efficient asymmetric hydrogenation of α-aminoacetophenone derivatives leading to practical synthesis of ()-(−)-levamisole,,10.1016/s0040-4039(00)95203-1,1989-01-01,0.6267133411358828
Journal of Organic Chemistry,Stereocontrolled Synthesis of a Possible Stereoisomer of Laurenidificin and a Formal Total Synthesis of (+)-Aplysiallene Featuring a Stereospecific Ring Contraction,"We report a highly stereocontrolled total synthesis of one of the possible stereoisomers of laurenidificin. Highlights of the synthesis include the formation of the 2,6-dioxabicyclo[3.3.0]octane framework by a stereospecific bromolactonization-α-bromination-ring contraction sequence, followed by a stereoselective propargylation, an insertion of the Z-enyne side chain by a hydroindation/cross coupling reaction, and ethylation at C13 with an organocuprate reagent. While the synthetic compound was not identical to the natural product, the absolute stereochemistry of the natural product was proposed on the basis of NMR analyses. Moreover, a formal total synthesis of (+)-aplysiallene was achieved by extending the ring contraction strategy.",10.1021/acs.joc.5b02595,2016-01-19,0.6266889382805421
Tetrahedron,Destannylative acylation of 1-[(2-methoxyethoxy)methoxy]-2-(phenylsulfonyl)-2-(tributylstannyl)cyclopropane: A novel route to 3-acylfurans,,10.1016/0040-4039(96)00852-0,1996-06-01,0.6266858451883295
Journal of Organic Chemistry,"Macrolactamization versus Macrolactonization: Total Synthesis of FK228, the Depsipeptide Histone Deacetylase Inhibitor","The cyclic depsipeptide FK228 is the only natural product histone deacetylase (HDAC) inhibitor that has advanced to clinical trials as an anticancer agent. While currently obtained by fermentation, total synthesis is an attractive alternative that will facilitate the preparation of unnatural analogues. The previous total syntheses of FK228 featured macrocylization by ester bond formation from a seco-hydroxy acid. Such routes are operationally jeopardized by the steric hindrance of the carboxylic acid and the sensitivity of the allylic alcohol toward elimination. We report a strategically different approach whereby the ester bond is formed intermolecularly at an early stage and macrocyclization is efficiently achieved by amide bond formation.",10.1021/jo801866z,2008-11-08,0.6266841186424672
Organic Letters,Diastereoselective Phenol <i>p</i><i>ara</i>-Alkylation:  Access to a Cross-Conjugated Cyclohexadienone en Route to Resiniferatoxin,"We document a route for the synthesis of a densely functionalized spiro-fused 2,5-cyclohexadienone as an intermediate for the synthesis of resineferatoxin. The strategy is based on an unprecedented diastereoselective, intramolecular phenol para-alkylation to a cross-conjugated cyclohexadienone. In the course of these synthetic studies we developed rapid access to a chiral nitrile possessing a quaternary stereocenter and disclose an unusual acetal rearrangement from a dioxane, which favors the corresponding dioxepane.",10.1021/ol0480832,2004-10-13,0.6266772372058587
Organic Letters,Improved and Flexible Synthetic Access to the Spiroindole Backbone of Cebranopadol,"By changing the dimethylamino to a nitro group, a novel synthetic access to the spirocyclic opioid analgesic cebranopadol was developed that is much more efficient compared with the established route. On the basis of the α-acidity of α-nitrotoluene, the two-fold Michael addition to acrylate gave an acyclic precursor compound, which was easily transformed by Dieckmann condensation and decarboxylation to the cyclohexanone derivative needed for the annulation of the indole ring by an oxa-Pictet–Spengler reaction. As an additional benefit, the reduction of the nitro group furnished an amine, which could be late-stage-diversified to carboxamides, sulfonamides, ureas, and N -alkyl congeners. The transformation of the nitro group at the spirocyclic scaffold to the dimethylamino function of the actual title compound was achieved in one step with zinc / formic acid/formaldehyde in 83% yield.",10.1021/acs.orglett.0c02234,2020-08-12,0.6266490194907938
Tetrahedron,Stereoselective synthesis of phosphinite complexes new route to chiral phosphines,,10.1016/s0040-4039(01)95466-8,1979-01-01,0.6266489153820008
Synlett,"New Synthesis of the Streptonigrin Quinoline-5,8-quinone Moiety and Aromatic Cross-Coupling","All articles of this category A new synthesis of quinoline-quinone moiety of Streptonigrin in nine steps with good overall yield (21%) is reported. The methodology involves metalation, a Heck coupling reaction, cyclization and oxidative demethylation.",10.1055/s-1994-22807,1994-01-01,0.6266443004249269
Tetrahedron,A simple synthetic route to a proposed intermediate in the biosynthesis of squalene from farnesyl pyrophosphate,,10.1016/s0040-4039(00)72297-0,1968-01-01,0.6266429973254997
Organic Process Research & Development,Process Safety Considerations for the Supply of a High-Energy Oxadiazole IDO1-Selective Inhibitor,The development of a stereospecific synthesis of a IDO1-selective inhibitor is described. The synthetic strategy toward enabling early discovery efforts along with additional findings pertaining to process safety that limited scalability are outlined. A convergent approach that supported the synthesis of material suitable for early preclinical and/or good laboratory practice toxicology studies and avoided the formation of key high-energy intermediates is summarized.,10.1021/acs.oprd.9b00105,2019-05-28,0.6266340182959401
Journal of the American Chemical Society,First Asymmetric Total Synthesis of Tetrodotoxin,"Tetrodotoxin, a toxic principle of puffer fish poisoning, is one of the most famous marine natural products because of the complex structure having many functional groups and its potent biological activity leading to death. Since the structure elucidation in 1964, this toxin has been recognized as a formidable target molecule for total synthesis. We have recently achieved the first asymmetric total synthesis from 2-acetoxy-tri-O-acetyl-d-glucal as a chiral starting material. The highly hydroxylated cyclohexane ring was constructed by Claisen rearrangement and regioselective hydroxylations of an acetone moiety and an intramolecular directed aldol condensation of the precursor having methyl ketone with dihydroxyacetone, which was synthesized through Sonogashira coupling. Installation of nitrogen functionality was unsuccessful through an attempted Overman rearrangement. We, therefore, employed a new intramolecular conjugate addition strategy between the carbamate and unsaturated ester groups. The alpha-hydroxyl lactone moiety was synthesized through an intramolecular epoxide opening by the Z-enolate of aldehyde, which was followed by oxidation-reduction of the resulting cyclic vinyl ether. The lactone was then converted to a protected ortho ester, and then gunanidinylation was followed by cleavage of the 1,2-glycol to give the fully protected tetrodotoxin. Selection of the protective groups has finally led us to accomplish the total synthesis of tetrodotoxin in an enantiomerically pure form. All the stereogenic centers were controlled with high selectivity, and the hydroxyl groups were differently protected to discriminate for the future analogue synthesis of a bioorganic program. The synthetic tetrodotoxin was purified by ion exchange chromatography and characterized to be identical with the natural compound.",10.1021/ja0342998,2003-06-28,0.6266326104201184
Tetrahedron,Novel synthetic strategy toward abietane and podocarpane-type diterpenes from (−)-sclareol: synthesis of the antitumor (+)-7-deoxynimbidiol,,10.1016/j.tetlet.2007.10.080,2007-11-06,0.6266276161794998
Organic Process Research & Development,"A New and Direct Asymmetric Synthesis of a Hindered Chiral Amine via a Novel Sulfinate Ketimine Derived from <i>N</i>-Tosyl-1,2,3-oxathiazolidine-2-oxide:  Practical Asymmetric Synthesis of (<i>R</i>)-Sibutramine","A novel and direct approach for the asymmetric synthesis of ( R )-sibutramine via chiral amine 5 using N -tosyl-1,2,3-oxathiazolidine-2-oxide ( 13 ) as a recyclable chiral auxiliary is described. Chiral sulfinate imine 16e was obtained by treatment of 13e with the imine intermediate formed from the reaction of a nitrile 1 and i BuMgCl that, upon reduction, provides an optically active amine 5 with high enantiopurity.",10.1021/op050182n,2006-01-10,0.6266248786538889
Tetrahedron,"Enantiospecific synthesis of SB 214857, a potent, orally active, nonpeptide fibrinogen receptor antagonist",,10.1016/0040-4039(95)02054-3,1995-12-01,0.6266086732644375
Organic Letters,Stereoselective Synthesis of the Macrolactone Core of (+)-Neopeltolide,"A stereoselective synthesis of the macrolactone core of the potent anticancer agent neopeltolide is disclosed. The key steps of the synthesis include asymmetric allylation using Krische' protocol, conjugate reduction using MacMillan's methodology, and an asymmetric hetero-Diels-Alder reaction using Jacobsen's catalyst. Substrate controlled diastereoselective 1,3-anti reduction of a keto alcohol, Luche reduction followed by Ireland-Claisen rearrangement, oxymercuration, and reductive lithiation are other key steps.",10.1021/ol3007698,2012-04-19,0.6265952611953435
Organic Letters,"A Concise, Phosphate-Mediated Approach to the Total Synthesis of (−)-Tetrahydrolipstatin","An efficient synthesis of (-)-tetrahydrolipstatin (THL) is reported. This method takes advantage of a phosphate tether-mediated, one-pot, sequential RCM/CM/hydrogenation protocol to deliver THL in eight total steps from a readily prepared (S,S)-triene. The strategy incorporates selective cross-metathesis, regioselective hydrogenation, regio- and diastereoselective cuprate addition, and Mitsunobu inversion for installation of the C5 formamide ester subunit.",10.1021/ol1002913,2010-03-02,0.6265952547278654
Journal of Organic Chemistry,"Synthetic Applications of 2-(1,3-Dithian-2-yl)indoles. 7. Synthesis of Aspidospermidine","A new method of synthesizing the alkaloid aspidospermidine (1), based on building ring E on the pyridocarbazole [ABCD] ring structure, is reported. The preparation of the pyridocarbazole framework of Aspidosperma alkaloids is a new three-step synthetic application of 2-(1,3-dithian-2-yl)indoles. A tandem conjugate addition-alkylation reaction starting from indolyldithiane (4), 3-methylenelactam 6, and EtI yields the adduct 17. Treatment of lactam 17 with DIBALH leads to formation of the naphthyridoindole 18. Compound 18 isomerizes in aqueous AcOH to yield pyridocarbazole 3. Finally, closure of ring E and subsequent reduction of the dithiane ring produces aspidospermidine. Pyridocarbazoles 2 and 10 were prepared as models.",10.1021/jo9609900,1996-01-01,0.626586356620504
Organic Letters,Enantioselective Total Synthesis of (+)-Jasplakinolide,"An enantioselective total synthesis of (+)-jasplakinolide is described. The synthesis of the polyketide template utilized a diastereoselective syn-aldol, ortho-ester Claisen rearrangement followed by efficient conversion to a cyanide. The beta-amino acid unit was constructed in a highly diastereoselective manner utilizing nucleophilic addition to a chiral sulfinimine. Yamaguchi macrocyclization and removal of the protecting group provided a convenient access to (+)-jasplakinolide.",10.1021/ol070855h,2007-05-08,0.6265783204966597
Organic Process Research & Development,Process Development of Voriconazole:  A Novel Broad-Spectrum Triazole Antifungal Agent,"In the synthesis of (2 R, 3 S )-2-(2,4-difluorophenyl)-3-(5-fluoro-4-pyrimidinyl)-1-(1 H -1,2,4-triazol-1-yl)-2-butanol (voriconazole), the relative stereochemistry is set in the addition of a 4-(1-metalloethyl)-5-fluoropyrimidine derivative to 1-(2,4-difluorophenyl)-2-(1 H -1,2,4-triazol-1-yl)-1-ethanone. The diastereocontrol of this reaction has been examined by variation of pyrimidine substitution pattern and by changes in the metalation and reaction conditions. Excellent diastereoselection (12:1) is obtained using an organozinc derivative of 6-(1-bromoethyl)-4-chloro-5-fluoropyrimidine. After removal of the chlorine from the pyrimidine ring, the absolute stereochemistry of voriconazole is established via a diastereomeric salt resolution process using (1 R )-10-camphorsulfonic acid. Synthetic routes to the pyrimidine partner have also been evaluated. The initial six-step development route from 5-fluorouracil has been superseded by a four-step synthesis involving fluorination of methyl 3-oxopentanoate and cyclisation with formamidine acetate.",10.1021/op0000879,2000-11-21,0.6265625056389161
Journal of the American Chemical Society,Synthesis and Absolute Stereochemistry of Roseophilin,"The enantiospecific total synthesis of natural roseophilin has been completed in 7.0% overall yield over 15 steps by means of an asymmetric cyclopentannelation. This establishes the absolute configuration of the natural product as 22R,23R. Cyclopentenone (+)-12 was prepared in 78% yield and 86% ee in the key step.",10.1021/ja011242h,2001-08-10,0.6265551052693078
Tetrahedron,Towards the total synthesis of aurodox: Preparation of the key hemiacetal-lactone,,10.1016/j.tetlet.2020.152799,2021-01-10,0.6265471994600272
Journal of the American Chemical Society,Total Synthesis of Roseophilin,"The first total synthesis of the antitumor agent roseophilin 1 is reported. Its intricate macrotricyclic core 2 is obtained by means of a new palladium-catalyzed manifold for the formation of ansa -bridged pyrroles which proceeds via vinyl oxirane 8 and allyl lactone 11 as key intermediates. After conversion of the latter into pyrrolophane 14, a base-induced elimination of the sulfone group followed by the Michael addition of a zincate onto the resulting enone 18 installs the isopropyl substituent in a stereoselective manner. The pyrrolylfuran side chain 3 of roseophilin is prepared from 4-methoxy-2(5H)-furanone ( 24 ) and methyl 4-chloropyrrole-2-carboxylate ( 26 ) as the starting materials. The appropriate building blocks 25a and 28 derived thereof are combined via a sequence comprising a directed metal−halogen exchange reaction, transmetalation of the resulting lithiopyrrole to the corresponding organozinc compound, a palladium-catalyzed cross coupling of the latter, and a subsequent acid-catalyzed closure of the resulting ketone 29 leading to the furan entity of the target. The triisopropylsilyl-protected side chain 3b is first deprotonated with n -BuLi and then transmetalated with CeCl 3 to give a highly nucleophilic organocerium reagent, which readily attacks the sterically hindered 2-(trimethylsilyl)ethoxymethyl-protected keto pyrrole 2c . Deprotection and final dehydration of the tertiary alcohol derivative 30 thus obtained leads to the intact azafulvene chromophore of the natural product and completes our total synthesis of this alkaloid.",10.1021/ja973846k,1998-03-12,0.6265337229930005
Journal of Organic Chemistry,"Scalable Total Syntheses of Some Natural and Unnatural Lamellarins: Application of a One-Pot Domino Process for Regioselective Access to the Central 1,2,4-Trisubstituted Pyrrole Core","Short and scalable total syntheses of lamellarin G trimethyl ether, lamellarin D trimethyl ether, lamellarin H, lamellarin η, dihydrolamellarin η, and lamellarin U have been realized in four to six linear steps with an overall yield of ≤22%. Highlights of the synthesis include single-step access to the central 1,2,4-trisubstituted pyrrole core in a highly regioselective manner via a one-pot [3+2] cycloaddition/elimination/aromatization sequence-based domino process. Subsequent, palladium-mediated double C-H oxidative coupling in a single-pot operation provides access to the pentacyclic coumarin-fused pyrrolo-dihydroisoquinoline core present in lamellarins.",10.1021/acs.joc.9b01521,2019-08-21,0.6265301428231801
Journal of Organic Chemistry,Asymmetric Total Synthesis of (+)-(3<i>E</i>)-Pinnatifidenyne via Abnormally Regioselective Pd(0)-Catalyzed Endocyclization,"The asymmetric total synthesis of the marine natural product (+)-(3E)-pinnatifidenyne was accomplished. The key features of the synthesis involve the construction of an eight-membered cyclic ether by the abnormally regioselective Pd(0)-catalyzed cyclization, the installation of a double bond in the oxocene skeleton by sequential in situ deconjugative isomerization, and the efficient introduction of the crucial chloride mediated by the substrate-controlled diastereoselective reduction.",10.1021/acs.joc.7b02937,2018-01-12,0.626517899181387
Journal of the American Chemical Society,Rifamycin Biosynthetic Congeners: Isolation and Total Synthesis of Rifsaliniketal and Total Synthesis of Salinisporamycin and Saliniketals A and B,"We describe the isolation, structure elucidation, and total synthesis of the novel marine natural product rifsaliniketal and the total synthesis of the structurally related variants salinisporamycin and saliniketals A and B. Rifsaliniketal was previously proposed, but not observed, as a diverted metabolite from a biosynthetic precursor to rifamycin S. Decarboxylation of rifamycin provides salinisporamycin, which upon truncation with loss of the naphthoquinone ring leads to saliniketals. Our synthetic strategy hinged upon a Pt(II)-catalyzed cycloisomerization of an alkynediol to set the dioxabicyclo[3.2.1]octane ring system and a fragmentation of an intermediate dihydropyranone to forge a stereochemically defined (E,Z)-dienamide unit. Multiple routes were explored to assemble fragments with high stereocontrol, an exercise that provided additional insights into acyclic stereocontrol during stereochemically complex fragment-assembly processes. The resulting 11-14 step synthesis of saliniketals then enabled us to explore strategies for the synthesis and coupling of highly substituted naphthoquinones or the corresponding naphthalene fragments. Whereas direct coupling with naphthoquinone fragments proved unsuccessful, both amidation and C-N bond formation tactics with the more electron-rich naphthalene congeners provided an efficient means to complete the first total synthesis of rifsaliniketal and salinisporamycin.",10.1021/jacs.6b03248,2016-05-27,0.6265150417560736
Journal of the American Chemical Society,Total Synthesis of Ningalin D,"A concise (nine-step) and effective (19% overall yield) total synthesis of ningalin D (1a) is disclosed and is based on a key 1,2,4,5-tetrazine --> 1,2-diazine --> pyrrole Diels-Alder strategy to assemble a fully substituted pyrrole core central to its structure. Additional highlights of the synthesis include a double Dieckmann condensation to introduce the C and D aryl rings enlisting substituents judiciously placed on the dienophile and intrinsic to the widely used tetrazine 2, a highly effective Suzuki coupling of the resulting C and D phenol triflates for introduction of the sterically demanding F and G aryl rings, and an unusually effective formal oxidative decarboxylation reaction cascade initiated by a Curtius rearrangement to directly provide the biphenylene quinone methide found imbedded in the structure of ningalin D. The cytotoxic and multidrug resistance (MDR) reversal activity of ningalin D, its derivatives, and the key synthetic intermediates are detailed.",10.1021/ja0526416,2005-07-07,0.6265012723814148
European Journal of Organic Chemistry,Decagram-Scale Synthesis of the Neocarzinostatin Carboxylic Acid,"Neocarzinostatin carboxylic acid (2) was synthesized on a 10-g scale in 9 steps and 43% overall yield from 3,5-dimethylanisol (9) (Schemes 5, 7). The hindered bromoarene 23, reached after 3 steps, underwent a high-temperature Heck coupling with ethyl acrylate, generating cinnamic ester 24. The C=C bond was reduced and the C≡N group methanolized to obtain diester 30. This underwent a regioselective Dieckmann cyclization, furnishing the dihydronaphthalene 13, that was then aromatized. The resulting ester 31 was carefully hydrolyzed such that the target acid 2 arose free from decarboxylation product 32.",10.1002/1099-0690(200007)2000:14<2605::aid-ejoc2605>3.0.co;2-y,2000-07-01,0.6264732011977573
Angewandte Chemie International Edition,"Total Syntheses of Bryostatins 1, 7, 9 and 9‐N<sub>3</sub>","Abstract Bryostatins are a family of marine natural products that have garnered significant interests, as evidenced by over 40 clinical trials. However, their extremely low natural abundance has severely limited further research. Despite significant efforts, which have led to the total synthesis of seven bryostatin members by eight independent research groups, these complex molecules present persistent challenges for stereocontrolled, large‐scale, and especially divergent synthesis. Here, we report the divergent total syntheses of bryostatins 1, 7, 9 and 9‐N 3 . Notably, 1.5 g of bryostatin 1 was obtained in a single sequence of the final three steps. Key transformations include Ni‐catalyzed reductive cross‐coupling to rapidly assemble the northern fragment, the flow chemistry‐assisted visible light‐induced alkyl radical conjugate addition to convergently construct the southern fragment, and an intramolecular geminal bis(silyl) Prins cyclization to establish the cis‐Z selectivity on the B‐ring. The syntheses consist of 20–22 steps in the longest linear sequence and 33–35 total steps, with overall yields ranging from 3.3 % to 4.5 %.",10.1002/anie.202423465,2025-01-20,0.6264597039007452
Organic Letters,Enantioselective Total Synthesis of Tricyclic Myrmicarin Alkaloids,"[reaction: see text] An enantioselective gram-scale synthesis of a key dihydroindolizine intermediate for the preparation of myrmicarin alkaloids is described. Key transformations in this convergent approach include a stereospecific palladium-catalyzed N-vinylation of a pyrrole with a vinyl triflate, a copper-catalyzed enantioselective conjugate reduction of a beta-pyrrolyl enoate, and a regioselective Friedel-Crafts reaction. The synthesis of optically active and isomerically pure samples of (4aR)-myrmicarins 215A, 215B, and 217 in addition to their respective C4a-epimers is presented.",10.1021/ol051629f,2005-08-27,0.6264585181717597
Organic Letters,"Total Synthesis of Incednam, the Aglycon of Incednine","The first total synthesis of incednam (1), the aglycon of antibiotic incednine (2), is described. Incednine has been reported to exhibit significant inhibitory activity against the antiapoptotic oncoproteins Bcl-2 and Bcl-xL. The synthesis of 1 commenced with the preparation of the C1-C13 subunit 3 and the C14-C23 subunit 4. The construction of the novel 24-membered macrocycle was achieved by the application of a Stille coupling between 3 and 4, followed by macrolactamization.",10.1021/ol102400c,2010-10-12,0.6264559049214337
Journal of the American Chemical Society,A Highly Stereoselective Total Synthesis of Hispidospermidin:  Derivation of a Pharmacophore Model,"The total synthesis of the title compound has been accomplished. Among the key steps were (i) a conjugate addition Robinson annulation-type sequence (see 4 ), (ii) intramolecular carbomercuration (see 3 ), (iii) a reduction−ketonization sequence (see 25 ), (iv) cycloetherification of an unactivated methylene group (see 28 ), and reductive amination (see 1 ). A highly preliminary SAR profile suggests that the functional cytotoxic pharmacophore of hispidospermidin involved a presentation of spermidine derivative 36 via linkage to a ball-like hydrophobic cage to its target.",10.1021/ja9944960,2000-06-13,0.6264556908706144
Tetrahedron,A Garratt–Braverman route to aryl naphthalene lignans,,10.1016/j.tetlet.2011.01.011,2011-01-13,0.6264499294823245
Synlett,A de novo Stereocontrolled Synthetic Approach to a Functionalized Indolizidine Core,"Abstract A convenient domino synthetic approach for the construction of the indolizidine core in diastereoselective manner has been developed from inexpensive starting compounds, providing triple functionalization. The novel synthetic route started from β-lactam derived from 1,5-cyclooctadiene including a ring-opening metathesis/cross-metathesis sequence as key steps with methyl acrylate followed by intramolecular ring closure across an aza-Michael addition. The process gave functionalized indolizidine framework with stereocontrol in high yields. DFT calculations supported the experimentally observed stereoselective reaction.",10.1055/s-0042-1751388,2022-11-23,0.6264475944197079
Synthesis,Approach to the Core Structure of 15-epi-Exiguolide,"The synthesis of seco acid 41 of the macrolactone part of 15-epi-exiguolide, containing a bis-pyran subunit and a trans double bond, is described. Key features of the synthetic strategy include a Feringa–Minnaard asymmetric organocuprate addition to unsaturated ester 17 to set the stereocenter at C15. The derived acid 8 (C9–C16 fragment) was ideally suited for combination with aldehyde 9 (C17–C21 fragment) via an aldol strategy leading to β-lactone 25 which upon thermal decarboxylation provided alkene 26. Chain extension led to propargylic alcohol 7. Treatment of 7 with a LAu+ catalyst promoted a Meyer–Schuster rearrangement to enone 30 that led to cis-tetrahydropyran 31 via intramolecular oxa-Michael reaction. The second pyran ring was prepared from alkoxy ketone 5 by reductive cyclization. The further steps toward macrolactone 43 were hampered by the epimeric mixture at C5.",10.1055/s-0037-1610821,2018-07-16,0.6264420854697539
Organic Letters,"Total Syntheses of (−)-Englerins A/B, (+)-Orientalols E/F, and (−)-Oxyphyllol","(-)-Englerin A was synthesized in 20 steps from the commercially available material ( R)-(+)-limonene. In addition, (-)-englerin B, (+)-orientalol E/F and (-)-oxyphyllol were obtained from the intermediate in the route. The key steps include a hydroxyl-directing stereoselective and regioselective intramolecular cyclopropanation and a multi-gram-scale stereoselective formal intramolecular [3 + 2] cross cycloaddition ([3 + 2]-IMCC) of a cyclopropane 1,1-diester with a carbonyl. A precursor of 7,10-diastereoisomer of englerins was also obtained.",10.1021/acs.orglett.8b00552,2018-04-17,0.6264095976630103
Organic Letters,Synthetic Studies Toward Pectenotoxin 2. Part I. Stereocontrolled Access to the C<sub>10</sub>−C<sub>22</sub> Fragment,A highly stereocontrolled and efficient synthesis for a fully functionalized C 10-C 22 fragment of pectenotoxin 2 is described using a convergent sequence involving a stereoselective methylation of beta-hydroxyketone as a key step.,10.1021/ol8015868,2008-09-03,0.6264090757961821
Organic Letters,Total Synthesis of Pseudodehydrothyrsiferol,An enantioselective total synthesis of pseudodehydrothyrsiferol has been accomplished. The synthetic sequence highlights formation of the highly strained tetrahydropyran C-ring by a Mitsunobu-type S(N)2 reaction with an oxygen nucleophile.,10.1021/ol802600n,2008-12-29,0.626403453731176
Synthesis,Organozirconium Chemistry on Cyclosporin: A Novel Process for the Highly Stereoselective Synthesis of (E)-ISA247 (Voclosporin) and Close Analogues,"Application of organozirconium chemistry to cyclosporin has led to the development of a novel process for the highly stereoselective synthesis of the E-isomer of ISA247 (voclosporin), which is a potent immunosuppressive agent currently in late stage human clinical trials for treatment of psoriasis, prevention of kidney transplant rejection, and ophthalmic indications. Synthesis of deuterated analogues of ISA247 and a cyclosporin triene analogue using the same methodology is also described.",10.1055/s-0031-1289616,2011-11-22,0.6264008986214937
Synlett,"Stereoselective Synthesis of (1<i>R</i>)-1-<i>C</i>-(6-Amino-7<i>H</i>-purin-8-yl)-1,4-anhydro-2,3-dideoxy-3-fluoro-D-<i>erythro</i>-pentitol<sup>1</sup>","All articles of this category The ""naked sugar"" (+)-(1 R ,2 S ,4 R )-2-cyano-7-oxa-bicyclo [2.2.1]hept-5-en-2-yl (1 S )-camphanate [(+)-3] (Diels-Alder adduct of furan with 1-cyanovinyl (1 S )-camphanate) was converted into (1 R )-1- C -(6-amino-7 H -purin-8-yl)-1,4-anhydro-2, 3-dideoxy-3-fluoro-D- erythro -pentitol [(+)-2] in nine synthetic steps and 12% overall yield.",10.1055/s-1992-21455,1992-01-01,0.6263916667669511
Journal of Organic Chemistry,A Novel Modular Approach to Triazole-Functionalized Phthalocyanines Using Click Chemistry,"A novel, elegant, and significantly improved protocol for the synthesis of a protected octaacetylene phthalocyanine is described. Inexpensive, mild, and environmentally benign iodination of 1,2-dibromobenzene and subsequent optimized chemoselective palladium-catalyzed cyanation are employed to effectively build up the key intermediate 4,5-dibromophthalonitrile in two steps. Introduction of the tert-butyldimethylsilyl-protected acetylene moieties via a Sonogashira cross-coupling provides the desired phthalonitrile precursor that, after cyclization, yielded the protected octaacetylene phthalocyanine. Subsequently, in situ deprotection and ""clicking"" are employed as a highly efficient and quantitative route to a novel class of octatriazole-functionalized phthalocyanines. The ability of such triazole-derived phthalocyanines to form well-defined supramolecular structures upon doping with zinc(II) triflate is demonstrated.",10.1021/jo802078f,2008-11-26,0.6263709955647153
Tetrahedron,A novel and efficient route to the construction of the 4-oxa-tricyclo[4.3.1.0]decan-2-one scaffold,,10.1016/j.tetlet.2007.07.005,2007-07-08,0.6263585146716707
Synlett,Concise Synthesis of the Terpene Core Structure of Suaveolindole through a Time-Economic Route,"Abstract The terpene core structure of suaveolindoles was synthesized through a concise route in a time-economical manner. A scalable synthetic route from pulegone delivered the desired α,β,γ,δ-unsaturated ester in a brief period. By way of Eschenmoser–Claisen rearrangement, carbon side-chain moiety at the crowded double-allylic position was introduced stereoselectively.",10.1055/a-1707-6593,2021-11-26,0.6263529894056461
European Journal of Organic Chemistry,A Short and Efficient Synthetic Strategy for the Total Syntheses of (<i>S</i>)‐(+)‐ and (<i>R</i>)‐(–)‐Plakolide A,"Abstract Concise and efficient total syntheses of anticancer agents ( S )‐(+)‐Plakolide A and ( R )‐(–)‐Plakolide A were accomplished in eight steps and an overall yield of 39 % starting from geraniol. The key steps in our strategy are Sharpless asymmetric epoxidation, double elimination, and Stille coupling reactions. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2007)",10.1002/ejoc.200700401,2007-08-07,0.62635056634187
Journal of the American Chemical Society,Total Synthesis of (±)-Communesin F,"Total synthesis of the complex polycyclic indole alkaloid (±)-communesin F has been accomplished in 23 reaction steps in about 3% overall yield. The key steps relied on a highly efficient methodology for assembling the pentacyclic substructure 2 with the C7 quaternary carbon, the stereoselective preparation of the second C8 quaternary carbon by a two-step one-pot O-allylation and consecutive 3,3-rearrangement ( 2 to 3 ), and the stereoselective acid-catalyzed cyclization of 4 to form the azepine ring ( 5 ). These highly stereoselective reactions guaranteed the stereochemical results, allowing the construction of the C, E, F, and G ring systems.",10.1021/ja075705g,2007-10-23,0.6263503484390088
Organic Letters,New Efficient Route to an Advanced Precursor of the AB Spiroketal of Spongistatins,"A sequence of highly diastereoselective functionalizations allowed transformation of a meso-methylenebis(cyclohept-3-ene-1,6-diyl diester) into an advanced precursor of the AB spiroketal of spongistatins. This route illustrates the potential of this bis-cycloheptene derivative for the synthesis of a key fragment of complex bioactive natural compounds.",10.1021/ol702326x,2007-11-01,0.6263503417171071
Organic Letters,Total Synthesis of Herbimycin A,Benzoquinone ansamycin antibiotic herbimycin A was synthesized in 19 linear steps and 4.2% yield. Highlighted is the design of a chiral γ-lactone as the C11-C15 synthon that enabled a facile catalytic asymmetric synthesis of the challenging C8-C20 fragment of the target molecule. The easy access to the stereogenic centers and high overall yield made the strategy applicable in the molecular editing of benzoquinone ansamycins.,10.1021/ol5012899,2014-06-09,0.6263500811516761
Synthesis,Synthesis of (Z)-2-[(tert-Butyldimethylsilyl)oxy]-3-(phenylthio) acrylaldehyde,"The title compound was prepared from ethyl acrylate over seven steps. En route, an ester was prepared that could be catalytically activated with Sc(OTf)3 to undergo a (4+3) cycloaddition with 2,5-dimethylfuran. The title compound reacts with organolithium species and the resultant alkoxide can be trapped as an ester or allowed to experience a silyl shift to produce a highly functionalized ketone.",10.1055/s-0036-1591597,2018-07-17,0.6263108135539447
Organic Letters,Total Syntheses of Grandilodines A and C and Lapidilectam via a Photoredox-Catalyzed Decarboxylative (6 + 2) Radical Annulation,"Herein, a unified approach to the concise total syntheses of grandilodine A, grandilodine C, and lapidilectam is described. Key steps in this synthesis include a sequential reductive amination/lactamization to assemble the pyrrolidinone structure, a gold-catalyzed 8- endo - dig cyclization to forge the central eight-membered ring, an effective photoredox-catalyzed decarboxylative (6 + 2) radical annulation to construct the rigid azabicyclic [4.2.2] framework featuring three contiguous stereocenters, and a late-stage modification of the lactam ring.",10.1021/acs.orglett.5c05094,2025-12-28,0.6263033868270895
Journal of Organic Chemistry,Synthesis of the Phosphoramidite Derivative of 2‘-Deoxy-2‘<i>-C-</i>β-methylcytidine,"2'-Deoxy-2'-C-beta-methylnucleosides elicit interest as potential therapeutic agents and as analogues for the analysis of nucleic acid structure and function. An efficient route for the synthesis of 2'-deoxy-2'-C-methyluridine (11), 2'-deoxy-2'-C-methylcytidine (12), and the phosphoramidite derivative of 2'-deoxy-2'-C-beta-methylcytidine (10, 46% overall yield) from 1,2,3,5-tetra-O-benzoyl-2-C-beta-methylribofuranose (1) is described.",10.1021/jo034263y,2003-07-22,0.6263030737787513
Synlett,A New Synthesis of l-Hydroxypipecolic Acid,"A new synthetic approach toward l-hydroxypipecolic acid is described. This reaction sequence involves eight steps overall, starting from commercially available and inexpensive l-glyceraldehyde acetal. The strategy makes use of readily available reagents and can be used as a preparative synthesis of l-hydroxypipecolic acid. Most of the reaction steps proceed with moderate-to-good yields and do not require any unusual or expensive reagents.",10.1055/s-0039-1690771,2020-01-07,0.6263006978189262
Synlett,A New Synthesis of Gefitinib,"A four-step synthesis of the FDA-approved anticancer agent gefitinib was developed starting from 2,4-dichloro-6,7-dimethoxyquinazoline. Reaction temperatures were highly practical (0–55 °C), and chromatographic purifications were avoided. The ionic liquid trimethylammonium heptachlorodialuminate was used to monodemethylate the dimethoxyquinazoline core. In the final step, a selective dehalogenation was employed to provide gefitinib in 14% overall yield on a gram scale.",10.1055/s-0037-1610375,2018-11-14,0.6262996267046504
Synthesis,"Convenient Synthesis of New N-3-Substituted Pyrido[1′,2′:1,5]pyrazolo[3,4-d]pyrimidine-2,4(1H,3H)-dione Derivatives","Previously unknown N-3-substituted pyrido[1′,2′:1,5]py­razo­lo[3,4- d ]pyrimidine derivatives were synthesized by a straightforward four-step synthesis. Starting from a 1-aminopyridinium salt, dimethyl acetylenedicarboxylate condensation followed by a fully regioselective saponification led to a pyrazolo[1,5- a ]pyridine monoester as a key intermediate. A Curtius rearrangement directly followed by amine condensation afforded a urea library. A final pyrimidine ring closure resulted in achievement of the heterocyclic construction. This straightforward strategy provides an efficient method to easily access a library of rare tricyclic scaffolds and highly valuable derivatives.",10.1055/s-0033-1338514,2013-07-25,0.6262962611667914
Organic Letters,Synthesis of an Isostere of an O-Linked Glycopeptide,"[reaction: see text] A route for the synthesis of an electrophilic, carbocyclic galactose equivalent from D-galactose is described. The strategy utilizes ring-closing metathesis with Grubbs's second-generation catalyst as the key step. The galactose-derived electrophile reacted in an S(N)2 fashion with N-Boc-cysteine methyl ester to provide an alpha-galactosylserine isostere. The method was extended to the synthesis of a glycopeptide isostere.",10.1021/ol0490779,2004-08-20,0.6262859832982535
European Journal of Organic Chemistry,"A Synthesis of (–)‐(<i>R</i>)‐ and (+)‐(<i>S</i>)‐Lavandulol, (+)‐Lavandulyl 2‐Methylbutanoate, and (+)‐Lavandulyl Senecioate through Orthoester Johnson–Claisen Rearrangement","Abstract An efficient synthesis of (–)‐( R )‐ and (+)‐( S )‐lavandulol, (+)‐lavandulyl 2‐methylbutanoate and (+)‐lavandulyl senecioate is presented in this paper. The synthetic strategy features a chiral‐pool approach to an allyl alcohol intermediate, and an orthoester Johnson–Claisen rearrangement as the key step.",10.1002/ejoc.201300520,2013-06-25,0.6262828137177091
Organic Process Research & Development,Improved Synthetic Process of Baloxavir Marboxil Intermediate 3-Benzyloxy-4-oxo-4<i>H</i>-pyran-2-carboxylic Acid,"The article presents a process research study of 3-benzyloxy-4-oxo-4 H -pyran-2-carboxylic acid ( 1 ), a crucial intermediate in the synthesis of baloxavir marboxil. The original four-step sequence exhibited various limitations, such as low yield (43%), the use of problematic solvents, a large excess of costly reagents, safety concerns, and impurity control difficulties. To address these challenges, process optimization was carried out to achieve the desired goals for large-scale industrial production. Optimization of the enamine 4b synthesis was performed, resulting in the development of an azeotropic removal method for the byproduct methanol. This improvement led to minimized ring-opening impurity 15 and a significant reduction in the consumption of the condensation reagent. Furthermore, a simplified one-pot two-step oxidation sequence was devised to streamline the process for the synthesis of compound 1 . This optimization involved controlling the formation of hydrolytic impurity 16 and its downstream aldol condensation form 17 . The optimized process was successfully demonstrated on a 600 g scale with a product purity of 99.9%, and the overall yield was substantially improved, rising from 43 to 66%.",10.1021/acs.oprd.2c00387,2023-06-02,0.6262762932116404
Journal of Organic Chemistry,Synthesis of a 3′-Fluoro-3′-deoxytetrose Adenine Phosphonate,"A new synthetic route to a 3'-fluoro-3'-deoxytetrose adenine phosphonate has been developed. The synthesis starts from l-xylose and key steps include the stereospecific introduction of the phosphonomethoxy group and adenine. In addition, a regioselective fluorination reaction allows access to the desired 3'-fluoro-3'-deoxytetrose moiety. This methodology allows the straightforward synthesis of a 3'-fluoro-3'-deoxytetrose adenine phosphonate and can be expanded toward the synthesis of other types of 3'-fluoro nucleoside phosphonates.",10.1021/acs.joc.7b01482,2017-08-29,0.6262687249749999
Organic Letters,Concise Synthesis of (+)-<i>allo</i>-Kainic Acid <i>via</i> MgI<sub>2</sub>-Mediated Tandem Aziridine Ring Opening–Formal [3 + 2] Cycloaddition,3-Methyl vinyl aziridine undergoes a mild MgI2-promoted S(N)2' ring opening and concomitant cyclization with fumarate Michael acceptors to give trisubstituted pyrrolidines. The process is efficient and highly diastereoselective. This methodology has been applied to a concise asymmetric synthesis of (+)-allo-kainic acid.,10.1021/ol4020333,2013-08-02,0.6262637263878781
Synlett,Total Synthesis and Cytotoxicity Evaluation of an Oxazole Analogue of Tubulysin U,"Tubulysins are strongly cytotoxic natural tetrapeptides with potent antiproliferative, antimitotic, and antiangiogenic activities which might find use in oncology. We herein report the first total synthesis of a stereoisomerically pure oxazole analogue of tubulysin U, which was found to be more cytotoxic than the thiazole-containing natural product. Additionally, we have developed an improved and scalable synthetic route towards the Tup fragment of the tubulysins.",10.1055/s-0030-1260806,2011-06-21,0.6262600573398033
European Journal of Organic Chemistry,A Concise and Efficient Total Synthesis of Oleocanthal,"Abstract Oleocanthal, one of the minor components of the phenolic fraction isolated from extra virgin olive oil, is an effective inhibitor of COX enzymes, possessing similar potency to the NSAID ibuprofen. Moreover, it has the capacity to alter the structure of neurotoxic Aβ‐amyloid oligomers (ADDLs) and to change the structure of deformed microtubule‐associated tau–protein, thus inhibiting the formation of neurofibrillary tangles. It can have, therefore, potential therapeutic use for the treatment of neurodegenerative diseases. In this paper we describe the total synthesis of (±)‐oleocanthal in just 8 steps (9 % overall yield) from easily available starting materials. Moreover, resolution of the racemic mixture on an HPLC chiral column provided both enantiomers of oleocanthal in a single operation for biological studies.",10.1002/ejoc.201300324,2013-05-23,0.6262572709422083
Journal of Organic Chemistry,"Efficient-One Pot Stereoselective Synthesis of Novel 2-Methyl-4-amino-1,2,3,4-Tetrahydroquinoline Derivatives","Efficient One-Pot Stereoselective Synthesis of Novel 2-Methyl-4-amino-1,2,3,4-Tetrahydroquinoline Derivatives.",10.1021/jo900729h,2009-04-24,0.6262555625456001
Organic Letters,Total Synthesis of (−)-Goniomitine,"The total synthesis of (-)-goniomitine has been accomplished in 11 steps starting from commercially available diethyl l-malate. The synthesis features a chiral pool approach to prepare the chiral C-9 unit containing a quaternary carbon center, an Ir-catalyzed C-H borylation to synthesize the 2-indoleboronic acid pinacol ester, and a Suzuki reaction to couple together the two key intermediates. Notably, the high degree of convergence of this strategy makes it particularly amenable to the total synthesis of other aspidosperma family natural products.",10.1021/ol501341b,2014-06-02,0.6262518913103075
Journal of the American Chemical Society,Enantioselective Total Synthesis of Mandelalide A and Isomandelalide A: Discovery of a Cytotoxic Ring-Expanded Isomer,"The total synthesis of mandelalide A and its ring-expanded macrolide isomer isomandelalide A has been achieved. Unexpected high levels of cytotoxicity were observed with the ring-expanded isomandelalide A with a rank order of potency: mandelalide A > isomandelalide A > mandelalide B. Key aspects of the synthesis include Ag-catalyzed cyclizations (AgCC's) to construct both the THF and THP rings present in the macrocycle, diastereoselective Sharpless dihydroylation of a cis-enyne, and lithium acetylide coupling with a chiral epoxide.",10.1021/jacs.5b12318,2016-01-13,0.6262436586395961
Synthesis,Asymmetric Synthesis of 2-Substituted (4<i>S</i>)-4-Aminopyrrolidines. S<sub>N</sub>2 Displacement at the 4-Position of the Pyrrolidine Moiety,"All articles of this category The trans -disubstituted- N -benzyl pyrrolidine 10 is prepared in enantiomerically homogeneous form from cis -4-hydroxy-D-proline (4) in an efficient sequence. The key step involves an S N 2 displacement of the methanesulfonate of alcohol 5 with azide ion and occurs without participation of the basic ring nitrogen. The stereochemical outcome, which is contrary to that reported for the related systems 15 and 16 , suggests that a mechanism involving the proposed intermediate 19a is improbable. The cis -derivative 14 is prepared by an identical sequence of reactions beginning with trans -4-hydroxy-L-proline. Compound 10 is the precursor to the potent DNA gyrase inhibitor 1 and several related analogs.",10.1055/s-1988-27459,1988-01-01,0.6262375220898481
Journal of Organic Chemistry,Novel and Efficient Access to Phenylamino-pyrimidine Type Protein Kinase C Inhibitors Utilizing a Negishi Cross-Coupling Strategy,"A novel, short, and efficient synthetic pathway to 3-{4-[2-(3-chlorophenylamino)-pyrimidin-4-yl]-pyridin-2-ylamino}-propanol (CGP 60474) and a series of analogues was developed. The synthetic sequence consisted of a Negishi-type cross-coupling reaction in the key step followed by two subsequent nucleophilic substitution reactions. This strategy represents a versatile and robust protocol to access diverse analogues of the title compound for subsequent SAR studies as potential phenylamino-pyrimidine type protein kinase C inhibitors.",10.1021/jo0505223,2005-05-21,0.6262236376325679
Organic Letters,Efficient Synthesis of the D-Ring Fragment of Cobyric Acid,"The synthesis of a highly functionalized 4,5-dihydro-3H-pyrrol, namely, the D-ring fragment 5a of cobyric acid (1), is described in this letter. A very efficient assembly to 5a involves CBS-reduction of 10, a [2,3] Wittig-Still rearrangement, and a stereoselective Michael addition to a nitro olefin.",10.1021/ol006337n,2000-09-09,0.6262235045168248
Tetrahedron,A stereoselective route to the spirobicyclic ring system of oscillatoxin D,,10.1016/0040-4039(91)80594-v,1991-08-01,0.6262162624095732
Tetrahedron,"Synthesis of a novel hexahydrofuro[3,4-b]furan derivative",,10.1016/s0040-4039(00)81918-8,1983-01-01,0.6262081066715475
Tetrahedron,"Synthesis and property of [6]-1,4-cyclophaneanthraquinone: A novel anthraquinone derivative undergoing photovalence isomerization",,10.1016/s0040-4039(00)91586-7,1992-02-01,0.6262081066715475
Angewandte Chemie International Edition,The Total Synthesis of Frondosin B,"The interleukin-8 receptor antagonist frondosin B (1) was synthesized in 12 steps from commercially available 5-methoxysalicylaldehyde in a completely regiocontrolled manner. The key steps of the synthesis were a Friedel – Crafts reaction to form the 7-membered ring and a Diels – Alder reaction to build the 6-membered ring, thereby fixing the double bond in the proper position.",10.1002/(sici)1521-3773(20000218)39:4<761::aid-anie761>3.0.co;2-i,2000-02-18,0.6262080492604265
Angewandte Chemie International Edition,The Total Synthesis of Frondosin B,"The interleukin-8 receptor antagonist frondosin B (1) was synthesized in 12 steps from commercially available 5-methoxysalicylaldehyde in a completely regiocontrolled manner. The key steps of the synthesis were a Friedel – Crafts reaction to form the 7-membered ring and a Diels – Alder reaction to build the 6-membered ring, thereby fixing the double bond in the proper position.",10.1002/(sici)1521-3773(20000218)39:4<761::aid-anie761>3.3.co;2-9,2000-02-18,0.6262080492604265
European Journal of Organic Chemistry,A Highly Stereoselective Total Synthesis of (+)‐9‐<i>epi</i>‐Dictyostatin,"Abstract The total synthesis of (+)‐9‐ epi ‐dictyostatin ( 1b ), a diastereomer of the antimitotic marine‐sponge‐derived macrolide (–)‐dictyostatin ( 1a ), was achieved by creating 11 stereogenic centers and 4 stereogenic double bonds with a high level of stereocontrol. The yield for the 29‐step longest linear sequence from Roche ester was 1.53 %. The final key steps to this unnatural product were the vinylzincate C10–C26 addition to aldehyde C1–C9 (leading surprisingly to a complete stereoselectivity for the 9 R ‐epimer), followed by Yamaguchi macrolactonization and global deprotection.",10.1002/ejoc.201001018,2010-09-20,0.6262046869195957
Organic Letters,"A Novel, Expeditious Synthesis of Racemic Camptothecin","[reaction: see text] A novel and efficient synthesis of racemic camptothecin, starting from a readily accessible hydroxy pyridone, is presented. Key steps include a Claisen rearrangement of a functionalized allylic ether, a hindered Heck coupling, and a Friedländer condensation.",10.1021/ol0509641,2005-06-10,0.626202753922164
Journal of Organic Chemistry,Asymmetric Allylboration and Ring Closing Alkene Metathesis:  A Novel Strategy for the Synthesis of Glycosphingolipids,"A novel strategy for the synthesis of D,L-glucosylceramide 1, a member of the glycosphingolipid class of natural products is described. Reagent-controlled asymmetric Brown allylboration gave excellent stereochemical control in the construction of adjacent stereocenters in the sphingoid base portion of the molecule. The trans-configured double bond was obtained as a single geometrical isomer by use of silicon-tethered olefin metathesis employing the Schrock carbene [(CF3)2MeCO]2Mo(=CHCMe2Ph)(=NC6H3-2,6-i-Pr2++ +) and in situ PhLi-induced ring-opening of the intermediate 5,6-dihydro-2H-1,2-oxasiline followed by protodesilylation with TBAF in DMSO. The synthesis was completed by long chain amide formation and global deprotection.",10.1021/jo000690p,2000-09-13,0.6261993193328631
Journal of Organic Chemistry,"Expedient One-Pot Synthesis of Novel Chiral 2-Substituted 5-Phenyl-1,4-benzodiazepine Scaffolds from Amino Acid-Derived Amino Nitriles","An efficient and stereocontrolled synthesis of phenylalanine- and tryptophan-derived 5-phenyl-1,4-benzodiazepines is described. This new methodology involves, as a key step, the synthesis of 5-phenyl-2,3-dihydro-1H-1,4-benzodiazepines by a one-pot cyano reduction and reductive cyclization of the appropriate amino nitrile, which were obtained via a modified Strecker reaction of N-protected alpha-amino aldehydes with 2-aminobenzophenone and trimethylsilyl cyanide. The subsequent reduction of these 2,3-dihydro-1H-1,4-benzodiazepines, followed by regioselective alkylation or acylation at position 4, led to 2,4-disubstituted-5-phenyl-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine.",10.1021/jo034286c,2003-05-01,0.6261911170889434
Synlett,Stereoselective Total Synthesis of psiAβ – A Sporogenic Psi Factor from Aspergillus nidulans,"The stereoselective total synthesis of psiAβ, a sporo­genic psi factor of the fungus Aspergillus nidulans , has been accomplished starting from pentane-1,5-diol. The synthesis involves an enantioselective Keck allylation, an asymmetric alkynylzinc addition, and a TEMPO–bis(acetoxy)iodobenzene (BAIB) oxidation as the key steps.",10.1055/s-0033-1340834,2014-02-13,0.6261819695274397
Organic Letters,Total Synthesis of (−)-Reveromycin B,"[structure: see text] The total synthesis of the epidermal growth factor inhibitor reveromycin B (2) is described. A novel, convergent, and stereoselective reaction sequence was utilized to construct the 5,6-spiroketal system 10 which was converted into the natural product 2 by a 16-step sequence.",10.1021/ol991281m,1999-12-23,0.6261812285597165
European Journal of Organic Chemistry,Asymmetric Total Synthesis of (−)‐Dehydrocostus Lactone by Domino Metathesis,"Abstract An efficient total synthesis of the sesquiterpenoid (−)‐dehydrocostus lactone is reported. Our earlier approach by a domino enediyne metathesis was extended by a domino dienyne metathesis strategy to give access to suitably functionalized hydroazulene cores. Highly stereoselective asymmetric anti aldol reactions provided the enantiopure substrates for this key step of our synthesis. Multiple hydroboration/oxidation of the resulting hydroazulenes set up three out of four stereogenic centers in a single step. First, oxidation to give a diketo‐γ‐lactone enabled an enantioselective formal synthesis of the target guaianolide. Subsequently, the final steps of this approach were improved by using a double carbonyl olefination at the stage of a masked γ‐butyrolactone, which completed the synthesis in a much more efficient way.",10.1002/ejoc.202100681,2021-06-08,0.6261751627002604
Synthesis,"Novel Two-Step Synthesis of N-Alkylated 2,3-Diaryl-4-quinolones",Abstract A library of 18 polysubstituted 4-quinolones was conveniently prepared via simple and practical protocol involving N-alkylation of 2-(3-oxoindolin-2-yl)acetonitriles and following NaH-induced ring expansion. The current two-step approach provides feasible access to a subclass of N-protected C3-aryl-substituted 2-phenyl-4-quinolones starting with or just one step away from commercially available 2-arylindoles and nitrostyrenes.,10.1055/s-0042-1751530,2023-12-06,0.6261689839717768
Tetrahedron,Dehydroascorbic acid (DHAA) capped magnetite nanoparticles as an efficient magnetic organocatalyst for the one-pot synthesis of α-aminonitriles and α-aminophosphonates,,10.1016/j.tetlet.2013.09.032,2013-09-25,0.6261653170602037
Organic Process Research & Development,"The Asymmetric Synthesis of (3<i>S</i>,4<i>R</i>,5<i>S</i>)-3-Amino-4,5-<i>O</i>-isopropylidenedioxycyclopentene","The title amine, an important substructure of nucleoside Q, is available from the 3,4-epoxycyclopentene in five steps. The epoxide is directly converted to the acetonide of cis -3, 4-dihydroxycyclopentene by treatment with boron trifluoride, a ring-opening with retention of configuration, a previously unknown process since known conversions of epoxides directly to acetonides normally involve initiating by nucleophilic opening of the epoxide with inversion of configuration. Two strategies were developed for diastereoselective allylic oxidation to cis -3,4- O -isopropylidenedioxy- trans -5-hydroxycyclopentene direct oxidation with selenium dioxide and a two-step process, epoxidation followed by base. The corresponding carbonate undergoes a palladium-catalyzed deracemization with phthalimide as nucleophile in 98% ee. Recrystallization can increase the ee to >99%. Removal of the phthalimide group to give the title compound occurs smoothly with ethylenediamine. Thus, a most efficient five-step synthesis (six steps from cyclopentadiene) contrasts with two recent asymmetric syntheses that required 12−16 steps.",10.1021/op025611l,2003-03-01,0.6261646573629859
Synthesis,"An Efficient Synthesis of 1,3-Benzothiadiazin-4(3H)-one 2-Oxides: Novel Anthranilic Acid Derivatives","Derivatives of anthranilic acid exhibit a range of useful biological activities. Herein we describe an efficient synthetic route to 1,3-benzothiadiazin-4(3 H )-one 2-oxides via copper-catalyzed N-arylation of sulfonimidamides followed by cyclization. Such 1,3-benzothiadiazin-4(3 H )-one 2-oxides can be viewed as novel anthranilic acid derivatives.",10.1055/s-0035-1561657,2016-06-15,0.6261555487970324
Synthesis,A Highly Efficient Asymmetric Synthesis of Homotaurine Derivatives via Diastereoselective Ring-Opening of γ-Sultones,"A highly efficient asymmetric synthesis of α,γ-substituted γ-amino sulfonates via diastereoselective ring-opening of enantiopure α,γ-substituted γ-sultones with inversion of configuration at the attacked γ-carbon is described. In the key step sodium azide is used as the nucleophilic nitrogen source. Secondary and tertiary γ-amino sulfonates were synthesized in very good yields and excellent diastereo- and enantiomeric excesses (de, ee ≥98%).",10.1055/s-2004-831256,2004-10-07,0.626153886821892
Tetrahedron,"A new synthetic route to aryl hydroxysulfonamides via a novel Fries-type rearrangement of aryl N,N-dialkylsulfamates",,10.1016/s0040-4039(01)01893-7,2001-12-01,0.6261500338129183
Angewandte Chemie International Edition,Total Synthesis of Incarnatapeptins A and B,"The first total synthesis of incarnatapeptins A and B, two novel marine natural products, was accomplished from readily available (S)-1-benzyloxycarbonylhexahydropyridazine-3-carboxylic acid. This route, whose longest linear sequence was 12 steps, provided the incarnatapeptins A and B in yields of 26.5 % and 19.7 %, respectively, and enabled the structure and stereochemistry of both natural products to be unambiguously confirmed. Highlights of our synthesis include the photoredox-mediated decarboxylative 1,4-addition reaction and a novel and practical N-acylation paradigm promoted by silver carbonate. The unusual facile atropisomerism of some linear peptidic intermediates was also observed by TLC analysis in the course of this work.",10.1002/anie.202317636,2024-01-19,0.6261417243335667
Journal of the American Chemical Society,Enantioselective Total Synthesis of (+)-Wortmannin,A concise and enantioselective total synthesis of the potent PI3K inhibitor (+)-wortmannin is described. A Pd-catalyzed cascade reaction was first developed to connect a synthon derived from Hajos-Parrish ketone to a furan moiety. The subsequent Friedel-Crafts alkylation of the β-position of a furan ring to an epoxide was optimized to establish the C10 quaternary center. (+)-Wortmannin was eventually accomplished by transformations following a late-stage oxidation of the furan allylic position. Kinome profiling and in vitro enzymatic assays were performed on 17-β-hydroxy-wortmannin and an epoxide analogue.,10.1021/jacs.7b02515,2017-05-05,0.6261289092966381
Synlett,Studies Towards a Total Synthesis of Amphidinolide B. Stereocontrolled Synthesis of the C14-C26 Polyol Fragment,"All articles of this category A practical synthesis of the C 14 -C 26 polyol unit 2 in amphidinolides B 1 and B 2 , 1 , is described which involves elaboration of the chiral unsaturated aldehyde 4 and the chiral ketone 5 , followed by crossed-aldolisation of 4 and 5 in the presence of LiHMDS at -78 °C, as key steps. Sharpless asymmetric epoxidation - silylstannylation - Sharpless asymmetric dihydroxylation - crossed-aldolisation",10.1055/s-1998-1701,1998-05-01,0.6261175897388283
Tetrahedron,"Synthesis of the Nonpeptide Renin Inhibitor A-68064 and the ACE Inhibitor Methyl Enalaprilat from (5S)-2,3,5,6-Tetrahydro-5-alkyl-N-(tert-butyloxycarbonyl-4H-1,4-oxazine-2-ones",,10.1016/s0040-4039(00)91678-2,1992-03-01,0.6260947309221693
Organic Letters,"Total Synthesis of Pleofugin A, a Potent Inositol Phosphorylceramide Synthase Inhibitor","X-ray analysis and total synthesis of 1 unambiguously confirmed pleofingin A's absolute configuration. The total synthesis was achieved by convergent assembly of three fragments (12, 14, and 18). This synthetic approach provides access to derivatives of 1 to search for antifungal agents that will be more effective in clinical use.",10.1021/acs.orglett.8b01930,2018-07-23,0.6260904856561328
Tetrahedron,Pd2+-promoted cyclization in tetracyclic diterpene synthesis highly diastereoselective formal total synthesis of (±)-stemodin,,10.1016/s0040-4039(00)73821-4,1993-09-01,0.626089333584527
Journal of Organic Chemistry,"A Stereocontrolled, Convergent Synthesis of Hydroxyethylene Dipeptide Isosteres","A simple, convergent, and stereoselective synthesis of hydroxyethylene dipeptide isosteres 1 and 2 from scalemic α-hydroxy esters has been developed. The method is short (six steps), efficient (≈15−25% overall), and highly diastereoselective (86−94% de) and enantioselective (>95% ee).",10.1021/jo970579s,1997-09-01,0.626082095284028
Journal of the American Chemical Society,Asymmetric Total Synthesis of Spongistatins 1 and 2,"The total synthesis of spongistatin 1 (1) and spongistatin 2 (2) has been achieved through an advanced-stage intermediate. The synthesis is highlighted by a highly convergent assembly of the four key fragments (the C1-C15 AB fragment 2, the C16-C28 CD fragment 3, the C29-C43 EF fragment 4, and the C44-C51 side chain 5) at a very advanced stage of the synthesis with minimal functional group interconversion. The CD fragment 3 functions as the central building block to which the other fragments are attached. The synthesis of the AB and CD spiroketal fragments is accomplished through the addition of a metalated gamma-pyrone to a beta-alkoxy aldehyde followed by spiroketalization. The EF subunit was assembled with high diastereoselectivity relying on asymmetric aldol reactions of chlorotitanium enolates of N-propionyl oxazolidinethiones and a double diastereoselective boron aldol to join the E and F fragments. Wittig coupling of the CD and EF fragments followed by a diastereoselective aldol reaction between the CDEF ketone and an AB aldehyde set the stage for attachment of the C44-C51 side chains and final macrolactonization and deprotection.",10.1021/ja0262683,2002-04-26,0.6260801894253083
Synlett,Enantioselective Synthesis of Cryptopleurine and Boehmeriasin A via Organocatalytic Intramolecular Aza-Michael Addition,"The enantioselective synthesis of phenanthroquinolizidine alkaloids cryptopleurine and boehmeriasin A was achieved in eight steps from commercial available Cbz-protected 2-piperidinone in 22% and 20% overall yield, respectively. The key steps of this route are intramolecular enantioselective aza-Michael addition, intramolecular aldol addition, and oxidative coupling.",10.1055/s-0031-1290457,2012-08-14,0.626077040961787
Organic Process Research & Development,A Scalable Synthesis of Tofogliflozin Hydrate,"A newly process for the synthesis of tofogliflozin hydrate, a sodium-glucose cotransporter type 2 (SGLT2) inhibitor, was described. Three improvements were achieved, including the development of a regioselective Friedel–Crafts reaction, a high-yield reduction, and a mild metal–halogen exchange. These improvements ultimately resulted in the isolation of tofogliflozin hydrate as a white solid in >99% purity (HPLC area) and 23% overall yield after 12 steps without column chromatography.",10.1021/acs.oprd.6b00175,2016-09-27,0.6260747247818301
Organic Letters,A Concise Synthesis of (+)-Salvadione B,"The novel hexacyclic triterpene salvadione B was synthesized in seven steps from the chiral quinone shown. The insight gained from this synthesis permitted a two-step, one-pot sequence to introduce the three additional rings and seven chiral centers.",10.1021/ol402010r,2013-09-16,0.6260705243487955
Tetrahedron,"Furanosteroid studies. Improved synthesis of the A,B,C,E-ring core of viridin",,10.1016/j.tetlet.2012.01.070,2012-01-30,0.626065335139374
Organic Letters,A New Entry to the Isogeissoschizoid Skeleton,"[reaction: see text] The tetracyclic isogeissoschizoid skeleton has been prepared by a novel route that involves the ozonolysis and double reductive amination of a cyclopentene, a nickel-catalyzed cyclization, and a late-stage Fischer indole synthesis.",10.1021/ol017213t,2002-01-19,0.6260539353556839
Journal of Organic Chemistry,Modular Total Synthesis of Farnesyl Analogues of Cell Wall Precursors Lipid I and II Containing the <i>Staphylococcus aureus</i> Pentaglycine Bridge Modification,A scalable and modular total synthesis of 3-lipid I and 3-lipid II was accomplished by a novel route involving an efficient solid phase synthesis of the peptide fragment and an effective chemoenzymatic attachment of the second sugar moiety. The generality of this route was further documented by the synthesis of an analogue bearing the pentaglycine interpeptidic bridge modification characteristic for the human pathogen Staphylococcus aureus .,10.1021/acs.joc.0c01004,2020-06-23,0.6260511314611665
Organic Letters,Total Synthesis of Pestalotioprolide E and Structural Revision of Pestalotioprolide F,"A short and convergent strategy for the first asymmetric total synthesis of cytotoxic macrolides pestalotioprolides E and F has been developed. The key features of this synthesis include Takai olefination, Sonogashira coupling, Ni-assisted partial hydrogenation of alkyne, modified Steglich reaction to generate the ester moiety, and intramolecular Horner-Wadsworth-Emmons (HWE) olefination to complete the macrocycle. This synthetic study revised the proposed structure of pesralotioprolide F.",10.1021/acs.orglett.8b01894,2018-07-17,0.6260483720149435
Organic Process Research & Development,Practical Asymmetric Synthesis of (+)-erythro Mefloquine Hydrochloride,A highly enantioselective and cost efficient process for the synthesis of (+)-erythro mefloquine has been developed. The key step is an enantioselective reduction of pyridyl ketone KI using transfer hydrogenation with formic acid as the hydrogen source. The ratio of formic acid to NEt 3 was found to be very important to achieving a highly efficient process.,10.1021/op200354f,2012-02-21,0.62604624957248
Tetrahedron,One-pot synthesis of new symmetric and asymmetric xanthene dyes,,10.1016/j.tetlet.2007.04.088,2007-04-23,0.6260452828093601
European Journal of Organic Chemistry,Synthesis of a Threosyl‐C‐nucleoside Phosphonate,"A general synthetic route for the preparation of the first analogue of a new series of sugar‐modified C‐nucleoside phosphonates is detailed. Such derivative contains a four‐carbon l ‐threose sugar moiety substituted with a phosphonomethoxy group at the 3′‐position and pyrrolo[2,1‐f][1,2,4]triazin‐4‐amine as nucleobase. A C‐nucleoside was initially prepared by coupling a benzyl protected l ‐threono‐1,4‐lactone intermediate with the corresponding aglycon moiety. The choice of a tert ‐butyldiphenylsilyl group was found to be crucial to achieve the regioselective protection of the hydroxyl group at the 3′‐position. Moreover, it allowed to smoothly perform further synthetic manipulations, including the introduction of a benzyl protected phosphonate synthon under basic conditions, which eventually led to the desired compound after final deprotection.",10.1002/ejoc.201901200,2019-10-14,0.6260427290378923
Journal of the American Chemical Society,Asymmetric Total Synthesis of Cerorubenic Acid-III,The first asymmetric total synthesis of the highly strained compound cerorubenic acid-III is reported. A type II intramolecular [5 + 2] cycloaddition allowed efficient and diastereoselective construction of the synthetically challenging bicyclo[4.4.1] ring system with a strained bridgehead (anti-Bredt) double bond in the final product. A unique transannular cyclization installed the vinylcyclopropane moiety with retention of the desired stereochemistry.,10.1021/jacs.8b12647,2019-02-05,0.6260324600077419
Tetrahedron,A new methylenecyclopropene synthesis and the isolation of a novel methylenecyclopropene dimer,,10.1016/s0040-4039(97)00085-3,1997-02-01,0.6260318229286094
Organic Letters,Enantioselective Synthesis of (−)-Dysiherbaine,"Dysiherbaine, a natural product isolated from the Marine sponge Dysidea herbacea, has been shown to be a selective agonist of non-NMDA type glutamate receptors, kainate receptors. An enantioselective synthesis of dysiherbaine is reported. Metathesis of the diene followed by conversion of the resulting alkene to the amino alcohol and addition of the amino acid provides the natural product. This synthesis differs from previous approaches to the molecule in that the functionality on the tetrahydropyran ring is installed late in the route.",10.1021/acs.orglett.5b01821,2015-08-10,0.6260233091327998
Journal of Organic Chemistry,Stereoselective Synthesis of (±)-Tetraponerine-2 and -4 via the Gold(I)-Catalyzed Intramolecular Dehydrative Amination of Allylic Alcohols,"The concise and efficient total synthesis of (±)-tetraponerine-2 ( T2 ) and (±)-tetraponerine-4 ( T4 ) was achieved in 9% and 14% overall yield, respectively. The key step included the diastereoselective gold(I)-catalyzed intramolecular dehydrative amination of an allylic alcohol-tethered sulfamide to produce the cis- 1,3-diamine moiety. The resulting olefinic side chain was then elaborated by cross-metathesis and cyclized to a five-membered pyrrolidine or a six-membered piperidine ring by intramolecular Mitsunobu N -alkylation. The unique tricyclic core of the (±)-tetraponerines was completed through cyclic sulfamide cleavage followed by aminal formation using 4-bromobutanal. This flexible synthetic strategy allows for the variation of the ring size, C-5 alkyl side chain length, and stereochemistry, which enables the preparation of diverse tetraponerine analogs for biological study.",10.1021/acs.joc.4c02365,2024-12-02,0.6260217963146325
Organic Letters,Multicomponent Linchpin Coupling of Silyl Dithianes Employing an <i>N</i>-Ts Aziridine as the Second Electrophile:  Synthesis of (−)-Indolizidine 223AB,"[reaction: see text] An efficient, stereocontrolled assembly of the indolizidine alkaloid, (-)-indolizidine 223AB, exploiting a three-component linchpin coupling employing an N-Ts aziridine as the second electrophile, followed by a one-pot sequential construction of the indolizidine ring system, has been achieved. The longest linear sequence was 10 steps, proceeding in 10% overall yield.",10.1021/ol049601b,2004-03-31,0.6260181784528462
Organic Letters,Total Synthesis of Integrastatin B Enabled by a Benzofuran Oxidative Dearomatization Cascade,"The first total synthesis of integrastatin B, a potent HIV-1 integrase inhibitor, has been accomplished in seven steps with a 17.9% overall yield employing easily accessible starting compounds. The Oxone-mediated oxidative benzofuran dearomatization cascade has been employed as the key skeletal construct to forge the central tetracyclic nucleus.",10.1021/acs.orglett.6b00404,2016-03-07,0.6260102640497028
Synthesis,"Nucleophilic Addition of Lewis Acid Complexed α-Amino Carbanions to Arynes: Synthesis of 1-Aryl-N-methyl-1,2,3,4-tetrahydroisoquinolines","The direct C-1 arylation of N -methyl-1,2,3,4-tetrahydroisoquinolines via coupling of α-amino carbanions derived from Lewis acid complexed tetrahydroisoquinolines and in situ generated arynes is described. This process provides an easy access to the title compounds and a new synthetic route to (±)-cryptostyline alkaloids.",10.1055/s-0033-1341239,2014-05-12,0.625987944927326
Organic Letters,De Novo Asymmetric Synthesis of Cladospolide B−D: Structural Reassignment of Cladospolide D via the Synthesis of its Enantiomer,"The enantioselective synthesis of cladospolide B, C, and (ent)-cladospolide D has been achieved in 11-15 steps from 1-nonyne. The route relies upon an alkyne zipper reaction to relay an ynone and dienoate functional groups across a nine carbon fragment, which enables a highly enantioselective Noyori ynone reduction and a diastereo- and regioselective Sharpless dihydroxylation of a dienoate. In addition to being a flexible approach to three members of the cladospolide natural products, this route for the first time correctly established the structure for cladospolide D.",10.1021/ol9000119,2009-02-04,0.6259838388324719
Journal of Organic Chemistry,"Total Synthesis of Anmindenol A and Its Application to the Design, Synthesis, and Biological Evaluation of Derivatives Thereof","The first total synthesis of anmindenol A is described in four steps. A notable feature of the synthetic route includes the efficient construction of the 3,10-dialkylsubstituted benzofulvene core via a stereoselective vinylogous Stork enamine aldol condensation. The strategy provided a blueprint for the practical preparation of derivatives with modifications in the C-10 alkyl substituents. The novel derivatives inhibited nitric oxide production in stimulated RAW 264.7 macrophage cells.",10.1021/acs.joc.9b01564,2019-07-30,0.6259810546726225
Synlett,First Asymmetric Synthesis of Piperidine Alkaloid (-)-Morusimic Acid D,"The first asymmetric synthesis of (-)-morusimic acid D, a 2,3-trans-2,6-cis-2-methyl-6-substituted piperidin-3-ol containing alkaloid is reported. The key steps are the reductive alkylation of N,O-diprotected 3-hydroxyglutarimide, a stepwise reductive alkylation, and an asymmetric aldol-type reaction using a modified Evans chiral auxiliary.",10.1055/s-2008-1072737,2008-04-25,0.625980189995908
European Journal of Organic Chemistry,Asymmetric Synthesis of a Pyrrolizidinone‐Based hNK<sub>1</sub> Antagonist through Reductive Ring Contraction of a Six‐Membered Cyclic Nitronate,"Abstract A concise seven‐step asymmetric synthesis of MSD's potent hNK 1 antagonist containing a pyrrolizidinone core bearing two fluorine‐substituted aryl groups was developed. The pyrrolizidinone unit was constructed by reductive recyclization of a properly functionalized cyclic nitronate, which was assembled by stereoselective [4+2]‐cycloaddition of a nitroalkene with a vinyl ether bearing a Whitesell's chiral auxiliary group. The configuration of the hNK 1 antagonist, which was previously suggested based on bioactivity data, was confirmed by X‐ray analysis. The crystal structure features multiple weak interactions involving fluorine atoms that are also found in a complex with the hNK 1 receptor simulated by molecular docking.",10.1002/ejoc.202200796,2022-08-31,0.625968713227124
Organic Letters,Total Synthesis of Epothilone B,"[structure-see text] A convergent and stereoselective total synthesis of epothilone B (2) is described. The key steps are Normant reaction, Wadsworth-Emmons reaction of a methyl ketone 14 with the phosphonate reagent 7, diastereoselective aldol condensation of aldehyde 3 with enolate 4 to form the C6-C7 bond, and macrolactonization.",10.1021/ol016173q,2001-10-13,0.6259675520328678
Synthesis,"A Short, Efficient Synthesis of Substituted Uracil: An Indane Carbocyclic Nucleoside","All articles of this category (±)- cis -1-(3-Hydroxymethyl-1-indanyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione ( 1 ) was synthesised in two steps and with an overall yield of 51% from (±)- cis -3-amino-1-indanylmethanol ( 4 ) and 3-ethoxy-2-propenoyl isocyanate ( 3 ). The isocyanate 3 was prepared in 76% overall yield by reacting silver cyanate with 3-ethoxy-2-propenoyl chloride ( 2 ), which was obtained in one pot from ethyl vinyl ether and oxalyl chloride. The aminoalcohol ( 4 ) was prepared from phenylsuccinic anhydride in four steps. synthesis - antiviral agent - antineoplastic agent - carbocyclic nucleoside - uracil derivative",10.1055/s-2001-10811,2001-01-01,0.6259647666007822
Synthesis,A Novel Synthesis of a Key Intermediate for (+)-Biotin from L-Aspartic Acid,"The aldol reaction of an N-Cbz-3-amino-4-butanolide 4, derived from l-aspartic acid, with formaldehyde gave the trans-disubstituted 3-amino-4-butanolide 5 stereoselectively. Following protection of the hydroxyl group of 5, amidation and oxidation provided the β-substituted l-asparagine derivative 6. The Hofmann rearrangement of 6 with sodium hypochlorite in the presence of sodium hydroxide and subsequent hydrogenation gave the bicyclic lactone 11, which upon dibenzylation and thionation, gave the thiolactone 2, a key intermediate for the synthesis of (+)-biotin (1).",10.1055/s-2002-20035,2002-01-01,0.6259575329517546
Journal of the American Chemical Society,"Efficient Access to the Core of the <i>Strychnos</i>, <i>Aspidosperma</i> and <i>Iboga</i> Alkaloids. A Short Synthesis of Norfluorocurarine","An efficient anionic bicyclization of tryptamine-derived Zincke aldehydes forms the basis for a three-step route to the tetracyclic ABCE core of many Strychnos, Aspidosperma, and Iboga alkaloids. This powerful reaction is showcased in a five-step synthesis of the Strychnos alkaloid norfluorocurarine from tryptamine and pyridine.",10.1021/ja900640v,2009-02-24,0.6259509331935106
Journal of Organic Chemistry,Synthesis of a Bicyclic Analogue of AZT Restricted in an Unusual O4‘-<i>Endo</i> Conformation,"The [3.2.0]bicyclic beta-nucleoside analogue 5 has been designed as a conformationally restricted analogue of the anti-HIV drug AZT. The synthesis of 5 as well as its alpha-anomer 29 is hereby described. The synthesis was accomplished from D-arabinose via a modified Corey-Link procedure stereoselectively incorporating the azide moiety as well as a methyl ester function. When the tert-butyldiphenylsilyl group was used as a permanent protecting group, a selective formation of an oxetane ring failed. When using the p-methoxyphenyl group as a permanent protecting group, 5 and 29 were efficiently obtained via a selective reduction of the ester, a nucleobase coupling followed by separation of the anomers and ring-closing procedures. The nucleoside 5 is conformationally restricted in an unusual O4'-endo (East) conformation, which is an intermediate between the North- and South-type conformations. Nevertheless, neither 5 nor 29 displayed any anti-HIV activity.",10.1021/jo010299j,2001-06-08,0.625945274048658
Tetrahedron,Thermolytic ring opening of acyloxybenzocyclobutenes: an efficient route to 3-substituted isoquinolines,,10.1016/s0040-4039(00)98697-0,1985-01-01,0.6259452607142656
Journal of Organic Chemistry,One-Step Synthesis of the Tricyclic Core of Martinellic Acid from 2-(Cyanomethyl)-3-oxo-<i>N</i>-arylbutanamides,A SnCl4.5H2O-mediated facile and efficient one-step synthesis of the tricyclic core of martinellic acid from readily available 2-(cyanomethyl)-3-oxo-N-arylbutanamides was developed and a mechanism involving consecutive hydrolysis of a cyano group and a double annulation process is proposed.,10.1021/jo701551f,2007-11-14,0.6259438878966453
Tetrahedron,New synthesis of 7-(tert-butoxycarbonyl)-7-azabicyclo[2.2.1]hept-2-ene. A key intermediate in the synthesis of epibatidine and analogs,,10.1016/s0040-4039(98)01077-6,1998-07-01,0.6259373320047437
Journal of Organic Chemistry,Short and Practical Synthesis of <i>O</i>-(<i>p</i>-Biphenoyl)-<i>N-</i>tosyl-<i>a</i><i>llo</i>-threonine-Derived Oxazaborolidinone Catalyst,"O-(p-Biphenoyl)-N-tosyl-(L)-allo-threonine methyl ester is synthesized in three steps (65% overall yield) starting from commercially available (L)-allo-threonine methyl ester hydrochloride by N-acylation followed by N,O-acyl migration with inversion of the beta carbinol carbon and N-tosylation. Treatment of the methyl ester with dibromophenylborane gives oxazaborolidinone 1, which can be used as a Lewis acid catalyst for the asymmetric Michael and Diels-Alder reactions.",10.1021/jo0522299,2006-01-07,0.6259053590157594
Synlett,"Diastereoselective Synthesis of Diamino 1,2-Diols from Homochiral α-Aminoacylsilanes","All articles of this category We have developed a new synthetic access to stereodefined diamino 1,2-diols starting from homochiral α -aminoacylsilanes. A [3 + 2] cycloaddition with benzo nitrile oxide of the vinylated adducts and a reductive ring opening constitute key steps of the reaction sequence. α -aminoacylsilanes - vinylation - dipolar cycloaddition - aminopolyols",10.1055/s-2001-14644,2001-01-01,0.6258971303046368
Organic Letters,A Nitrone Dipolar Cycloaddition Strategy toward an Enantioselective Synthesis of Massadine,"An enantioselective route to the C,D-bicycle of massadine is reported. Enantiopure intermediates were generated by a single stereoselective reduction using the Corey-Bakshi-Shibata reagent. This initial stereoinduction was translated into the five contiguous stereocenters of the massadine D-ring by a synthetic route that features a diastereoselective and stereospecific Ireland-Claisen rearrangement of a trianionic enolate followed by a diastereoselective nitrone dipolar cycloaddition of a highly electron-poor oxime.",10.1021/acs.orglett.8b01464,2018-06-13,0.6258891845968757
Tetrahedron,The absolute configurations of (+)-thalictrifoline and (+)-corydalic acid methyl ester. Total synthesis of (+)-thalictrifoline.,,10.1016/s0040-4039(01)82899-9,1981-01-01,0.6258793496666114
Organic Process Research & Development,"Development of the Enabling Route for a Novel HCV NS3/4A Inhibitor, Furaprevir","Furaprevir demonstrated adequate safety and effectiveness in clinical phases I and II, which was identified as a potent Hepatitis C virus (HCV) NS3/4A protease inhibitor. Research on the synthesis process of Furaprevir is insufficient, so a reliable manufacturing procedure is required to support subsequent clinical trials. There were two challenging steps in the synthesis process, which involved an amide-bond formation and a ring-closing metathesis (RCM) reaction to form the product active pharmaceutical ingredient (API). The optimized process conditions were successfully used to produce 25 kg per batch of Furaprevir, which was sufficient to support the subsequent clinical development and onward.",10.1021/acs.oprd.1c00315,2022-02-18,0.6258511602177391
European Journal of Organic Chemistry,"Highly Diastereo- and Enantioselective Synthesis of Protectedanti-1,3-Diols","An efficient asymmetric synthesis of protected anti-1,3-diols 5 (de ≥ 98%, ee = 92-98%) from 2,2-dimethyl-1,3-dioxan-5-one SAMP hydrazone 1 is described. The key steps are the diastereo- and enantioselective α,α′-bisalkylation followed by reduction of the ketones 2 and a variant of the Barton–McCombie deoxygenation. The new method allows the synthesis of acetonide-protected anti-1,3-diols with a broad range of substituents in good overall yields (31-69%).",10.1002/(sici)1099-0690(199812)1998:12<2839::aid-ejoc2839>3.0.co;2-7,1998-12-01,0.6258423326048126
Tetrahedron,Synthesis of a new macrocyclic ligand with six amide receptor sites,,10.1016/0040-4039(96)00626-0,1996-05-01,0.6258406541064739
Organic Letters,A New Enantioselective Total Synthesis of AI-77-B,"An enantioselective total synthesis of AI-77-B ( 1 ), a gastroprotective substance isolated from a culture broth of Bacillus pumilus AI-77, was performed in high overall yield. In this synthesis, the dihydroisocoumarin part 14 and the dihydroxyamino acid part 20 were both assembled from d -ribose as the common chiral source. For the construction of 14 a bromobenzofuran derivative was used as a novel salicylic acid synthon. Finally, DEPC-mediated condensation of 14 and 20 yielded AI-77-B ( 1 ).",10.1021/ol990102y,1999-06-25,0.6258380800080265
Angewandte Chemie International Edition,Stereocontrolled Total Synthesis of (+)‐Streptazolin by a Palladium‐Catalyzed Reductive Diyne Cyclization,"(+)-Streptazolin synthesis revisited: The key reaction in the 11-step total synthesis of (+)-streptazolin (3), which starts from D-mannitol diacetonide, is the palladium-catalyzed reductive cyclization of two alkyne arms in 1 to provide the desired 1,3-diene 2 with the correct defined geometry. TBS=tert-butyldimethylsilyl.",10.1002/anie.200460058,2004-08-13,0.6258025021906203
Synthesis,Asymmetric Hydrogenation of 2-Benzylidenesuccinic Acid 4-[(4-BOC-amino)-1-piperidide] Monoamide: Key Step in a Process for Large Scale Preparation of a Renin Inhibitor,All articles of this category The N -terminal component 4 of an orally active renin inhibitor is prepared on kg-scale by asymmetric hydrogenation of the title compound 3 . Enantioselectivities of several homogeneous homochiral rhodium(I)- and ruthenium(II)-diphosphine catalysts are compared.,10.1055/s-1994-25511,1994-01-01,0.6257927553714887
Synthesis,Synthesis of the β-Lactamase Indicators Cefesone and Nitrocefin,"All articles of this category The synthesis of the β -lactamase indicators Cefesone [(6 R ,7 R )-3-(2,4-dinitrostyryl)-7-(phenylacetamido)ceph-3-em-4-carboxylic acid] and Nitrocefin [(6 R ,7 R )-3-(2,4-dinitrostyryl)-7-(2-thienylacetamido)ceph-3-em-4-carboxylic acid] from tert -butyl (1 S ,6 R ,7 R )-3-bromomethyl-1-oxo-7-(phenylacetamido)ceph-3-em-4-carboxylate is reported. Phosphonylation of the latter compound with triphenylphosphine gave the corresponding phosphonium derivative in 93% yield. Reduction followed by Wittig coupling with 2,4-dinitrobenzaldehyde gave a 1 : 12 mixture of E - and Z -isomers in 83% yield. The tert -butyl protecting group was removed with titanium tetrachloride to give Cefesone as the pure crystalline E -isomer in 63% yield. De-acylation was achieved by enzymatic hydrolysis in 77% yield. Finally the 2-thienylacetyl side chain was introduced to give crystalline Nitrocefin in 67% yield. Cefesone - cephalosporin - Nitrocefin - β -lactamase indicator - penicillin acylase",10.1055/s-1998-2018,1998-02-01,0.6257846070061891
Journal of the American Chemical Society,Total Synthesis of Kendomycin:  A Macro−<i>C</i><i>−</i>Glycosidation Approach,"Kendomycin, also known as (-)-TAN 2162, is a novel polyketide-derived ansamycin isolated from Streptomyces sp., which exhibits potent antagonist and agonist activities at the endothelin and calcitonin receptors, respectively. This bacterial metabolite also possesses a strong antibiotic activity against a range of gram-positive and -negative bacteria and cytostatic effects on the growth of human cancer cell lines. When a novel macroglycosidation reaction is employed as the key step, the first enantioselective total synthesis of kendomycin has been accomplished. A Friedel-Crafts-type ring closure of the acyclic precursor containing tetrahydropyran and benzofuran moieties produces the macrocycle as a single stereoisomer in good yield, thus establishing the aryl C-glycosidic linkage of the ansa core. This reaction requires a phenolic glycosyl acceptor and appears to proceed through a rapid O-glycosidation followed by a slow rearrangement to an aryl C-glycoside. The requisite secomacrocycle is prepared by the Pd(0)-catalyzed B-alkyl Suzuki-Miyaura cross-coupling of two subunits, which in turn can be expeditiously assembled from readily available building blocks in a modular fashion.",10.1021/ja0447154,2004-10-27,0.625779163332507
Journal of Organic Chemistry,"Stereoselective Synthesis of CF<sub>2</sub>-Substituted Phosphothreonine Mimetics and Their Incorporation into Peptides Using Newly Developed Deprotection Procedures<sup>,</sup>","Stereoselective syntheses of all four stereoisomers of CF(2)-substituted nonhydrolyzable phosphothreonine derivatives (33, 39, and their enantiomers) and their incorporation into peptides are described herein. Key to the synthesis of these amino acids was construction of secondary phosphate-mimicking difluoromethylphosphonate units along with generation of two stereocenters. The former was achieved using a Cu(I)-mediated cross-coupling reaction of BrZnCF(2)P(O)(OEt)(2) (8) and beta-iodo-alpha,beta-unsaturated ester 12, with stereochemistry of both alpha- and beta-stereocenters being established using bornane-10,2-sultam as a chiral auxiliary. Diastereoselective hydrogenation of a chiral alpha,beta-unsaturated acylsultam (for the beta-center) (e.g., 16a) and subsequent stereoselective bromination (for the alpha-center of the threo derivative) or amination (for the alpha-center of erythro (allo) derivative) were utilized. Transesterification of the bromide to the benzyl ester followed by azide displacement of the halogen, then reduction of the resulting azide, followed by Boc-protection and finally removal of the benzyl group, afforded protected both L- and D-phosphothreonine mimetics (39 and its enantiomer). On the other hand, protected both L- and D-allo-phosphothreonine mimetics (33 and its enantiomer) were synthesized via transesterification of the above-mentioned amination product, followed by hydrogenolytic removal of the benzyl group. Key to utilization of these amino acid analogues in peptide synthesis was removal of ethyl protection from the difluoromethylphosphonate moiety. A two-step deprotection methodology, consisting of a combination of a first-step reagent [0.3 M BSTFA-TBAI in CH(2)Cl(2), BF(3).Et(2)O] followed by a second-step reagent [1 M TMSOTf-thioanisole in TFA, m-cresol, EDT] was developed for use in solid-phase protocols. A 12-residue Cdc (cell division cycle) 2-peptide 41, possessing two nonhydrolyzable phosphoamino acid mimetics (F(2)Pmab 6 and F(2)Pmp 4), was subjected to this deprotection procedure and was obtained in 25% yield based on the protected resin. The present synthetic method affords nonhydrolyzable phosphoamino acid mimetics-containing peptides in high yield without accompanying side reactions.",10.1021/jo000169v,2000-07-11,0.6257782589016009
Organic Process Research & Development,An Efficient Catalytic Asymmetric Synthesis of a β<sup>2</sup>-Amino Acid on Multikilogram Scale,"We describe herein a scalable catalytic asymmetric hydrogenation process for the multikilogram-scale production of a β 2 -amino acid. A short and efficient synthesis of the starting unsaturated N -Boc-protected β 2 -enamide was developed followed by extensive catalysis screening and optimization studies that identified a simple Ru-BINAP catalyst system to directly afford the ( S ) product in high enantiomeric excess and yield. The final process enabled the multikilogram production in >99% ee, to be used as a key component for one of our clinical candidates.",10.1021/op4002966,2013-12-26,0.6257771368242985
Journal of the American Chemical Society,Direct Generation of Triketide Stereopolyads via Merged Redox-Construction Events: Total Synthesis of (+)-Zincophorin Methyl Ester,"(+)-Zincophorin methyl ester is prepared in 13 steps (longest linear sequence). A bidirectional redox-triggered double anti-crotylation of 2-methyl-1,3-propane diol directly assembles the triketide stereopolyad spanning C4-C12, significantly enhancing step economy and enabling construction of (+)-zincophorin methyl ester in nearly half the steps previously required.",10.1021/jacs.5b05296,2015-07-13,0.6257745154458692
Organic Letters,Enantioselective Synthesis of the Predominant AB Ring System of the <i>Schisandra</i> Nortriterpenoid Natural Products,An enantioselective synthesis of the AB ring system common to the majority of the Schisandra nortriterpenoid natural products is reported. Key steps include a stereospecific ring opening of a trisubstituted epoxide and the use of a β-lactone to enable installation of the gem-dimethyl functionality of the B ring. An acetalization strategy played a key role in a late-stage biomimetic AB ring bicyclization.,10.1021/ol502027m,2014-08-15,0.6257624772696253
Angewandte Chemie International Edition,Enantioselective Desymmetrization of meso-Decalin Diallylic Alcohols by a New Zr-Based Sharpless AE Process: A Novel Approach to the Asymmetric Synthesis of Polyhydroxylated Celastraceae Sesquiterpene Cores,Zirconium to the rescue! Eight contiguous chiral centers can be established with >95 % ee in the key step of an asymmetric synthetic approach to the cores of certain Celastraceae sesquiterpenes (see scheme). The route required the development of a new zirconium-modified Sharpless asymmetric epoxidation instead of the traditional titanium version. DIPT=diisopropyl tartrate.,10.1002/1521-3773(20010216)40:4<769::aid-anie7690>3.3.co;2-x,2001-02-16,0.6257576726978741
Angewandte Chemie International Edition,Enantioselective Desymmetrization of meso-Decalin Diallylic Alcohols by a New Zr-Based Sharpless AE Process: A Novel Approach to the Asymmetric Synthesis of Polyhydroxylated Celastraceae Sesquiterpene Cores,Zirconium to the rescue! Eight contiguous chiral centers can be established with >95 % ee in the key step of an asymmetric synthetic approach to the cores of certain Celastraceae sesquiterpenes (see scheme). The route required the development of a new zirconium-modified Sharpless asymmetric epoxidation instead of the traditional titanium version. DIPT=diisopropyl tartrate.,10.1002/1521-3773(20010216)40:4<769::aid-anie7690>3.0.co;2-5,2001-02-15,0.6257576726978741
Angewandte Chemie International Edition,A Relay Route for the Synthesis of Azadirachtin,"22 Years in the making: Azadirachtin (1) was synthesized for the first time by a highly convergent approach, utilizing a Claisen rearrangement and a radical cyclization as key steps. End-game strategies relied on intermediate 2, which could be obtained by synthetic methods as well as by degradation of 1. Bn=benzyl, TBS=tert-butyldimethylsilyl.",10.1002/anie.200703028,2007-07-30,0.6257485079760685
Tetrahedron,The synthesis of a key intermediate of tricyclic beta-lactam antibiotics,,10.1016/0040-4039(95)00740-4,1995-06-01,0.6257469474117738
Synlett,Synthesis of a Racemic Nicotine-Lobeline Hybrid,The first synthesis of a racemic nicotine-lobeline hybrid is described based on a diastereoselective allylation and an RCM reaction as key steps. This synthetic route paves the way to the preparation of original potential ligands of nAChRs.,10.1055/s-0029-1219966,2010-06-10,0.6257458956490456
Angewandte Chemie International Edition,Total Synthesis and Stereochemical Reassignment of (±)‐Indoxamycin B,"Revised version: the first total synthesis of indoxamycin B leads to a stereochemical reassignment of the natural product. The synthetic route features an efficient carboannulation sequence to rapidly access the dihydroindenone system. Moreover, a series of Au(I)-catalyzed transformations served in the construction of the sterically congested core framework.",10.1002/anie.201109175,2012-02-17,0.6257391258533034
Organic Letters,Divergent Entry to <i>C</i>-Glycosides from Unprotected Sugars,"An efficient, divergent, and straightforward access to novel C-glycosides has been developed, namely, α-hydroxy carboxamide and carboxylic acid derivatives, via a green and scalable process from unprotected carbohydrates. The method involves condensation of 1,3-dimethylbarbituric acid with unprotected sugars followed by subsequent barbiturate oxidative cleavage in the same pot. Further expanding of the chemistry led to the development of efficient entries to diastereoisomerically pure C-glycosyl-α-hydroxy esters or amides through nucleophilic attack on a readily available and versatile key lactone intermediate.",10.1021/acs.orglett.9b00666,2019-03-27,0.6257263364231098
Organic Letters,Application of Aryl Siloxane Cross-Coupling to the Synthesis of Allocolchicinoids,"In this communication, we report a new approach to the allocolchicine carbocyclic skeleton based upon an aryl siloxane coupling reaction and a phenanthrol ring expansion. These key steps allow for the selective functionalization of every carbon within the carbocyclic framework. The siloxane coupling-phenanthrol sequence was applied to the synthesis of two allocolchicinoids, including the first fully synthetic approach to N-acetyl colchinol-O-methyl ether (NCME).",10.1021/ol061413t,2006-08-01,0.6257259189079162
Organic Letters,Stereoselective Access to the Core Structure of Macroline-Type Indole Alkaloids: Total Synthesis of Macroline and Alstomicine,"Rapid synthesis of the pentacyclic core structure of macroline-type indole alkaloids, and its application in the total synthesis of macroline and alstomicine is described. The core structure was accomplished in a highly stereocontrolled manner via two key steps, Ireland-Claisen rearrangement and Pictet-Spengler cyclization, commencing from a readily available starting material l-tryptophan, which obviated the need of a particular chiral source as an external catalyst, reagent, or internal auxiliary.",10.1021/acs.orglett.8b01921,2018-08-01,0.625715083271874
Synthesis,"New, Scalable Process for the Preparation of 5-Acetyl-1H-pyrazole-3-carboxylic Acid, a Key Intermediate of Darolutamide","Abstract A new, efficient process for the synthesis of 5-acetyl-1H-pyrazole-3-carboxylic acid, a versatile building block and the key intermediate of darolutamide, using diethyl pyrazole-3,5-dicarboxylate as the starting material is described. Contrary to the synthetic routes known from the literature, this procedure does not employ explosive diazo reagents, moreover it is simple and safe, thereby suitable for scale-up.",10.1055/a-2016-4337,2023-01-19,0.6257101940140116
European Journal of Organic Chemistry,A Synthetic Route to α‐Substituted Butenolides: Enantioselective Synthesis of (+)‐Ancepsenolide,Abstract A variety of α‐substituted butenolides was efficiently synthesized starting from commercially available tetronic acid and carboxylic acids in four steps. The effectiveness of this approach is illustrated in the short synthesis of one of the first butenolide acetogenins: (+)‐ancepsenolide.,10.1002/ejoc.201100491,2011-05-18,0.6257094825825289
Organic Letters,Synthesis of the AviMeCys-Containing D-Ring of Mersacidin,A chemical synthesis of the D-ring of mersacidin is reported. The synthetic route relied upon development of a method for late-stage introduction of an unusual S-[(Z)-2-aminovinyl]-(3S)-3-methyl-D-cysteine (AviMeCys) functional group via an oxidative decarbonylation/decarboxylation reaction.,10.1021/ol2034806,2012-02-01,0.6257085606260456
Organic Letters,An Intra/Intermolecular Suzuki Sequence to Benzopyridyloxepines Containing Geometrically Pure Exocyclic Tetrasubstituted Alkenes,"A route to enable the preparation of 5-benzylidenyl-benzopyridyloxepine analogues was developed to continue our research in the field of nuclear hormone receptor modulators. The key steps are 1) a syn-stereoselective diboration of a tethered aryl alkyne; 2) an intramolecular Suzuki cross-coupling reaction, which forms in a stereo- and regiocontrolled fashion, the 5-exoalkylidenyl 7-membered ring imbedded within the core of the scaffold and; 3) an intermolecular Suzuki to furnish the final tetra-substituted olefinic benzopyridyloxepines.",10.1021/ol800834q,2008-06-07,0.6256978301797139
Synlett,Synthesis of Tetrahydrofurans through a Novel Pseudo-<i>meso</i>-trick,Diastereoselective synthesis of trisubstituted tetrahydrofuran (d-lyxo-4) from the equimolar diastereomeric mixture of d-erythro- /d -threo-1-pentenitols (1) is described. The synthesis exploits a sequence of two novel reactions: diastereospecific palladium(II)-catalyzed bicyclization of pentenitols 1 with degeneration of the allylic stereogenic center and subsequent regioselective ring-opening of bicyclic skeleton 2.,10.1055/s-2005-869840,2005-05-12,0.6256889494976968
Angewandte Chemie International Edition,Enantioselective Total Synthesis of Andrographolide and 14‐Hydroxy‐Colladonin: Carbonyl Reductive Coupling and <i>trans</i>‐Decalin Formation by Hydrogen Transfer,"An enantioselective total synthesis of the labdane diterpene andrographolide, the bitter principle of the herb Andrographis paniculata (known as ""King of Bitters""), was accomplished in 14 steps (LLS). Key transformations include iridium-catalyzed carbonyl reductive coupling to form the quaternary C4 stereocenter, diastereoselective alkene reduction to establish the trans-decalin ring, and carbonylative lactonization to install the α-alkylidene-β-hydroxy-γ-butyrolactone.",10.1002/anie.202011363,2020-09-09,0.6256843914480449
Tetrahedron,Synthetic studies on halichondrins: A new practical synthesis of the C.1–C.12 segment,,10.1016/s0040-4039(00)60394-5,1993-11-01,0.6256832090029758
Organic Letters,Total Synthesis of Vinorine,"The asymmetric total synthesis of vinorine, a polycyclic and cage-like alkaloid, has been realized in a flexible approach. Key features of the current synthesis include an aza-Achmatowicz rearrangement/Mannich-type cyclization to install the highly functional 9-azabicyclo-[3.3.1]nonane scaffold, a high yield Fischer indole annulation to synthesize the common intermediate for sarpagine-ajamaline type alkaloids, and an Ireland-Claisen rearrangement to construct the C15-C20 bond.",10.1021/acs.orglett.3c01041,2023-05-08,0.6256821704023968
Journal of Organic Chemistry,"General Approach for the Synthesis of Sarpagine Indole Alkaloids. Enantiospecific Total Synthesis of (+)-Vellosimine, (+)-Normacusine B, (−)-Alkaloid Q<sub>3</sub>, (−)-Panarine, (+)-<i>N</i><sub>a</sub>-Methylvellosimine, and (+)-<i>N</i><sub>a</sub>-Methyl-16-epipericyclivine","The first total synthesis of (+)-Na-methyl-16-epipericyclivine (9) was completed [from d-(+)-tryptophan methyl ester] in an overall yield of 42% (eight reaction vessels). The optical rotation [[alpha]D +22.8 (c 0.50, CHCl3)] obtained on this material confirmed that the reported optical rotation [[alpha]D 0 (c 0.50, CHCl3)]47 was biogenetically unreasonable. The total syntheses of (+)-vellosimine, (+)-normacusine B, (-)-alkaloid Q3, (-)-panarine, and (+)-Na-methylvellosimine are also described. Moreover, a mixed sample (1:1) of synthetic (-)-panarine and natural (-)-panarine yielded only one set of signals in the 13C NMR; this indicated that the two compounds are identical and further confirmed the correct configuration of (+)-vellosimine, (+)-normacusine B, and (-)-alkaloid Q3. In this approach, the key templates, (-)-Na-H,Nb-benzyltetracyclic ketone 15a and (-)-Na-methyl,Nb-benzyltetracyclic ketone 43 were synthesized on multihundred gram scale by the asymmetric Pictet-Spengler reaction and a stereocontrolled Dieckmann cyclization via improved sequences. An intramolecular palladium (enolate-mediated) coupling reaction was employed to introduce the C(19)-C(20) E-ethylidene function in the sarpagine alkaloids for the first time in stereospecific fashion.",10.1021/jo030006h,2003-04-18,0.625671998243635
Tetrahedron,"Toward the synthesis of mycalamides A, B and onnamide A: a highly stereoselective synthesis of the trioxadecalin ring system",,10.1016/s0040-4039(00)73924-4,1993-01-01,0.6256625826921051
Organic Letters,Protecting-Group-Free Total Synthesis of (−)-Jiadifenolide: Development of a [4 + 1] Annulation toward Multisubstituted Tetrahydrofurans,"A concise, protecting-group-free total synthesis of (-)-jiadifenolide, a synthetically challenging seco-prezizaane sesquiterpene with potent neurotrophic activity, is reported. The convergent route features a SmI2/H2O-mediated stereoselective reductive cyclization, an unprecedented formal [4 + 1] annulative tetrahydrofuran-forming reaction and programmed redox manipulations. The newly developed annulation of β-hydroxy aldehydes or ketones with lithium trimethylsilyldiazomethane provides access to a diverse array of multisubstituted tetrahydrofurans. The synthetic jiadifenolide exhibited weak cytotoxicity against five human cancer cell lines.",10.1021/acs.orglett.5b02845,2015-10-28,0.6256464546741575
Synlett,An Enantioselective Deprotonation Route to a Versatile Intermediate for<i>C</i>-Nucleoside Synthesis,"All articles of this category The asymmetric transformation of ketone 1 ( exo - cis -6,7-isopropylidenedioxy-8-oxabicyclo[3.2.1]octan-3-one) into optically active silyl enol ether 2 ( exo - cis -6,7-isopropylidenedioxy-3-trimethylsiloxy-8-oxabicyclo[3.2.1]oct-2-ene) in up to 85% ee was achieved using the homochiral lithium amide base 6 [lithium ( R,R )-bis(1-phenylethyl)amide]. Conversion of 2 into a known key intermediate 3 (methyl 2,3- O -isopropylidene-ß-ribofuranosyl-acetate) for C -nucleoside synthesis was possible in a highly efficient two-step sequence.",10.1055/s-1991-34734,1991-01-01,0.6256379116691266
Journal of the American Chemical Society,Total Synthesis of Amphidinolide E,A convergent and highly stereocontrolled synthesis of amphidinolide E (1) has been accomplished. The synthesis features a highly diastereoselective (>20:1) BF3.Et2O promoted [3+2] annulation reaction between aldehyde 3 and allylsilane 4 to afford substituted tetrahydrofuran 2.,10.1021/ja066663j,2006-11-30,0.6256333218683336
Tetrahedron,Selective phenol alkylation for an improved synthesis of 2-arylbenzimidazole H4 receptor ligands,,10.1016/j.tetlet.2009.03.033,2009-03-14,0.6256313944859083
Journal of Organic Chemistry,Synthesis of a Next-Generation Taxoid by Rapid Methylation Amenable for <sup>11</sup>C-Labeling,"Next-generation taxoids, such as SB-T-1214, are highly potent cytotoxic agents that exhibit remarkable efficacy against drug-resistant tumors in vivo, including those that overexpress the P-glycoprotein (Pgp) efflux pump. As SB-T-1214 is not a substrate for Pgp-mediated efflux, it may exhibit a markedly different biodistribution and tumor-accumulation profile than paclitaxel or docetaxel, which are both Pgp substrates. To investigate the biodistribution and tumor-accumulation levels of SB-T-1214 using positron emission tomography (PET), a new synthetic route has been developed to allow the incorporation of 11 C, a commonly employed positron-emitting radionucleide, via methyl iodide at the last step of chemical synthesis. This synthetic route features a highly stereoselective chiral ester enolate–imine cyclocondensation, regioselective hydrostannation of the resulting β-lactam, and the Stille coupling of the novel vinylstannyl taxoid intermediate with methyl iodide. Conditions have been established to allow the rapid methylation and HPLC purification of the target compound in a time frame amenable to 11 C-labeling for applications to PET studies.",10.1021/acs.joc.7b03284,2018-02-14,0.6256274605260405
Journal of Organic Chemistry,"Enantioselective Nitrile Anion Cyclization to Substituted Pyrrolidines. A Highly Efficient Synthesis of (3 <i>S</i> ,4 <i>R)</i> -N- <i>tert</i> -Butyl-4-Arylpyrrolidine-3-Carboxylic Acid","[reaction: see text] A practical asymmetric synthesis of N-tert-butyl disubstituted pyrrolidines via a nitrile anion cyclization strategy is described. The five-step chromatography-free synthesis of (3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidine-3-carboxylic acid (2) from 2-chloro-1-(2,4-difluorophenyl)-ethanone achieved a 71% overall yield. The cyclization substrate was prepared via a catalytic CBS asymmetric reduction, t-butylamine displacement of the chlorohydrin, and a conjugate addition of the hindered secondary amine to acrylonitrile. The key nitrile anion 5-exo-tet cyclization concomitantly formed the pyrrolidine ring with clean inversion of the C-4 center to afford 1,3,4-trisubstituted chiral pyrrolidine in >95% yield and 94-99% ee. Diethyl chlorophosphate and lithium hexamethyldisilazide were shown to be the respective optimum activating group and base in this cyclization. The trans-cis mixture of the pyrrolidine nitrile undergoes a kinetically controlled epimerization/ saponification to afford the pure trans-pyrrolidine carboxylic acid target compound in >99.9% chemical and optical purity. This chemistry was also shown to be applicable to both electronically neutral and rich substituted phenyl substrates.",10.1021/jo050178+,2005-04-01,0.6256233128234588
Organic Letters,"Highly Enantioselective Total Synthesis of (−)-(3′<i>S</i>)-Lomatin and (+)-(3′<i>S</i>,4′<i>R</i>)-<i>trans</i>-Khellactone","Concise highly enantioselective three-step syntheses are described for (-)-(3'S)-lomatin and (+)-(3'S,4'R)-trans-khellactone from 7-hydroxycoumarin in 97% ee and in 57% and 58% overall yields, respectively, using nonaqueous enantioselective epoxidation by an iminium salt as the key step.",10.1021/ol900444h,2009-04-08,0.625618547271214
Journal of the American Chemical Society,Enantioselective Synthesis of (+)-Cephalostatin 1,"This Article describes an enantioselective synthesis of cephalostatin 1. Key steps of this synthesis are a unique methyl group selective allylic oxidation, directed C-H hydroxylation of a sterol at C12, Au(I)-catalyzed 5-endo-dig cyclization, and a kinetic spiroketalization.",10.1021/ja906996c,2009-12-07,0.6256176485760221
Synlett,An Approach to β-Substituted γ-Butyrolactones and its Application to the Synthesis of Lignans,"Copper-catalyzed reaction of 4-cyclopentene-1,3-diol monoacetate with ArCH2MgCl afforded 4-arylmethyl-2-cyclopenten-1-ols regioselectively. Subsequent cleavage of the cyclopentene ring followed by functional group manipulation provided the key β-arylmethyl-γ-butyrolactones for the synthesis of lignans. In addition, synthesis of the rolipram lactone intermediate was accomplished.",10.1055/s-2004-830890,2004-08-06,0.6256175595481632
Journal of the American Chemical Society,Total Synthesis of (+)-Brasilenyne. Application of an Intramolecular Silicon-Assisted Cross-Coupling Reaction,"The first enantioselective total synthesis of (+)-brasilenyne (1) has been achieved in 19 linear steps, with 5.1% overall yield from l-(S)-malic acid. The construction of the oxonin core containing a 1,3-cis,cis diene unit was accomplished with a tandem ring-closing metathesis/silicon-assisted intramolecular cross-coupling reaction. In addition, a key propargylic stereogenic center was created through a novel, highly diastereoselective ring opening of a 1,3-dioxolanone promoted by TiCl(4). This reaction proceeded through an oxocarbenium ion intermediate and the asymmetric induction was fully controlled by l-malic acid residue. The C(8) stereogenic center was set by a reagent-controlled asymmetric allylboration.",10.1021/ja0466863,2004-09-14,0.625614916240849
Angewandte Chemie International Edition,A Unified Approach for the Assembly of Atisine‐ and Hetidine‐type Diterpenoid Alkaloids: Total Syntheses of Azitine and the Proposed Structure of Navirine C,"A tetracyclic dinitrile was synthesized in twelve steps from cyclohex-2-en-1-one by using a chelation-triggered conjugate addition to a γ-hydroxy-substituted α,β-unsaturated nitrile and an oxidative dearomatization/Diels-Alder cycloaddition cascade as the key steps. The first total synthesis of azitine (in 17 steps) was achieved through a simple reductive cyclization of this intermediate and subsequent transformations while the total synthesis of the proposed structure of navirine C (in 19 steps) was accomplished by a hydrogen-atom-transfer reaction of the tetracyclic dinitrile, Pd/C-catalyzed reductive cyclization, and subsequent functional group manipulation.",10.1002/anie.201803018,2018-04-03,0.6256111206832543
Organic Letters,"Diethyl 2,7-Dibromo-4 <i>H</i> ,5 <i>H</i> - thieno[3,2- <i>b</i> :4,5- <i>b</i> ‘]dipyrrole-3,6- dicarboxylate:  A Key Intermediate for a Diversity Oriented Synthesis of 2,7,12,17-Tetraarylporphycenes","A new Suzuki-based strategy for the synthesis of 4,4'-diaryl (or heteroaryl)-substituted 2,2'-bipyrroles (10), precursors of 2,7,12,17-tetraaryl (or heteroaryl)-substituted porphycenes, is described. Bromination of the previously described diethyl 4H,5H-thieno[3,2-b:4,5-b']dipyrrole-3,6-dicarboxylate afforded dibromo compound 19, which is the key intermediate of such strategy.",10.1021/ol052913+,2006-01-31,0.6255966585199448
Tetrahedron,"A convenient synthesis of 2-exo-methylene penam, a potent intermediate for new β-lactam antibiotics synthesis",,10.1016/0040-4039(91)80130-x,1991-12-01,0.6255880624183039
Organic Process Research & Development,"Development of a Scalable Process for CI-1020, A Novel Endothelin Antagonist<sup>1</sup>","The process development of a route for preparing CI-1020 on pilot-plant scale is described in 55% overall yield. Hydrocyanation conditions are described which use acetone cyanohydrin catalyzed by tetramethylammonium hydroxide and which provide the desired ketonitrile intermediate ( 4 ) in 85% yield with excellent quality. The penultimate intermediate ( 7 ), a hydroxybutenolide, is prepared in a two-step process using an aldol condensation followed by acid-catalyzed ring closure to give product in 86.8% yield. The active pharmaceutical ingredient (API) ( 8 ) is prepared by ring-opening of the hydroxybutenolide with sodium carbonate to provide the sodium salt. The use of ReactIR to monitor the API reaction is described. ReactIR was required to determine an endpoint for the reaction. The use of chromatographic analysis to determine the endpoint was not possible. The API and the penultimate hydroxybutenolide are not separable by chromatographic methods.",10.1021/op010200a,2001-04-19,0.6255787419702155
Tetrahedron,Migration of methyl group in heptamethylbenzenonium ion a new route to perdeuterohexamethylbenzene,,10.1016/s0040-4039(01)84086-7,1965-01-01,0.6255765731963419
Organic Process Research & Development,Catalyst-Free and Scalable Process for Synthesis of Novel MAP4K4 Inhibitor DMX-5804 and Its Glyco-Conjugates,"DMX-5804 is a potent and selective mitogen-activated protein kinase kinase kinase kinase-4 (MAP4K4) inhibitor, which is currently under evaluation for the treatment of myocardial infarction. Here, we report the process development of scalable and practical synthesis of DMX-5804. Process optimization resulted in the following: (1) removal of transition metals from the process and reduced duration of reactions, (2) a streamlined process with significantly improved yields using low-cost raw materials, (3) importantly, microwave-assisted reactions were removed, (4) column purification avoided throughout the process, and (5) crystallized products showed over 95% purity in each step.",10.1021/acs.oprd.1c00130,2021-07-08,0.6255654885657285
Organic Process Research & Development,Development of a Commercial Process for Odalasvir,"Odalasvir is a selective inhibitor of hepatitis C virus NS5A protein, a key target for combination therapies. This paper describes the chemical process development for the synthesis of this active pharmaceutical ingredient and the improvements that were achieved over the medicinal chemistry route. Optimization of all of the reaction conditions and crystallizations resulted in higher throughput and a highly improved process mass intensity. The process is robust and has been scaled up to ∼100 kg batches without issues.",10.1021/acs.oprd.1c00237,2021-12-15,0.6255585016076216
Organic Letters,Total Synthesis of (−)-Ascochlorin via a Cyclobutenone-Based Benzannulation Strategy,The application of a convergent benzannulation strategy in an efficient synthesis of (-)-ascochlorin is described.,10.1021/ol006561c,2000-09-23,0.6255483310426236
Synlett,Synthesis of (+)-Leukotriene B<sub>4</sub>(LTB<sub>4</sub>) Methyl Ester and (-)-(5<i>R</i>)-LTB<sub>4</sub>Methyl Ester via Pyrylium Methodology,"All articles of this category The title compounds (5 S )- and (5 R )-leukotriene B 4 methyl esters ( 1 ) and ( 2 ), have been prepared from 3-nonenal by a short convergent synthetic route which utilises addition of 3-( tert -butyldimethylsiloxy)-1,5-undecadienyllithium ( 8 ) to pyrylium tetrafluoroborate for the construction of the crucial Z,E,E -triene unit.",10.1055/s-1992-21283,1992-01-01,0.6255474792307847
Tetrahedron,An efficient total synthesis of neopatulin,,10.1016/s0040-4039(00)78179-2,1994-08-01,0.6255255628457398
Tetrahedron,Efficient total synthesis of iso-cladospolide B and cladospolide B,,10.1016/j.tetlet.2005.07.153,2005-08-16,0.6255255628457398
Tetrahedron,An efficient total synthesis of (±)-isosarcophytol-a,,10.1016/s0040-4039(00)91902-6,1992-02-01,0.6255255628457398
Tetrahedron,An efficient total synthesis of (−)-anamarine,,10.1016/j.tetlet.2012.05.099,2012-06-02,0.6255255628457398
Tetrahedron,Efficient total synthesis of manzacidin B,,10.1016/j.tetlet.2012.04.042,2012-04-21,0.6255255628457398
Tetrahedron,Efficient total synthesis of the cytotoxic halogenated monoterpene aplysiapyranoid A,,10.1016/s0040-4039(00)77455-7,1993-02-01,0.6255255628457398
Tetrahedron,An efficient total synthesis of (−)-mintlactone and (+)-isomintlactone,,10.1016/s0040-4039(00)61320-5,1992-08-01,0.6255255628457398
Tetrahedron,An efficient total synthesis of chrysophanol and the sennoside C aglycon,,10.1016/j.tetlet.2005.08.154,2005-09-17,0.6255255628457398
Tetrahedron,An efficient total synthesis of (+)-Cladospolide C,,10.1016/j.tetlet.2009.03.036,2009-03-14,0.6255255628457398
Tetrahedron,An efficient total synthesis of calothrixin B,,10.1016/j.tetlet.2012.03.131,2012-04-04,0.6255255628457398
Tetrahedron,An efficient total synthesis of (±)-decaline and (±)-vertaline,,10.1016/s0040-4039(00)88022-3,1983-01-01,0.6255255628457398
Tetrahedron,An efficient total synthesis of (±)-isokhusimone,,10.1016/s0040-4039(98)01942-x,1998-11-01,0.6255255628457398
Tetrahedron,An efficient total synthesis of sulfobacin A,,10.1016/j.tetlet.2004.10.137,2004-11-12,0.6255255628457398
Tetrahedron,"An efficient total synthesis of 3′-azido-3′-deoxythymidine (AZT) and 3′-azido-2′,3′-dideoxyuridine (AZDDU, CS-87) from D-mannitol",,10.1016/s0040-4039(00)82864-6,1988-01-01,0.6255255628457398
Organic Letters,First Enantioselective Total Synthesis of (−)-Tejedine,"[structure: see text] The first enantioselective total synthesis of (-)-tejedine (1) is reported. Tejedine is a seco-bisbenzyltetrahydroisoquinoline isolated in 1998 as a minor component from Berberis vulgaris. The synthesis was achieved using a strategy employing four key steps, including a chiral auxiliary-assisted diastereoselective Bischler-Napieralski cyclization.",10.1021/ol0261635,2002-07-11,0.6255151879678695
Tetrahedron,"Synthesis of chiral 1,4-dihydropyridines by diastereoface-selective asymmetric addition to nicotinic amides",,10.1016/s0040-4039(99)00683-8,1999-05-01,0.6255081720058321
Synthesis,"A Facile Synthesis of 6-Methoxy-2-oxo-2,3-dihydrobenzoxazole","All articles of this category A new two-step synthesis of 6-methoxybenzoxazolin-2(3 H )-one, a bioactive natural product from Gramineae, is described. The new procedure avoids disadvantages of hitherto existing methods and affords the title compound in 75% overall yield from 5-methoxy-2-nitrophenol.",10.1055/s-1989-27420,1989-01-01,0.6255060321728071
Synlett,A Concise Asymmetric Total Synthesis of (+)-8-Epigrosheimin via Catalyst-Free Tandem Allylboration–Lactonization,"Abstract A concise and scalable asymmetric synthesis of (+)-8-epigrosheimin is reported in nine steps using only three column chromatographic purifications with an overall yield 47.0% from (R)-(–)-carvone. Two synthetic routes are evaluated by catalyst-free tandem allylboration–lactonization of two carvone-derived aldehydes and subsequent ene cyclization, where strategy via Lee–Lay aldehyde is found to be more effective for 8-epigrosheimin.",10.1055/a-2413-0587,2024-09-10,0.6254979943948562
Angewandte Chemie International Edition,Hidden Symmetry Enables a 15‐Step Total Synthesis of Pactamycin,"Inside insight: Pactamycin has long been recognized as a potent bioactive compound and a formidable target for chemical total synthesis. Recently, Johnson and co-workers published a 15-step enantioselective synthesis of pactamycin that capitalized on the recognition of latent symmetry in the core structure.",10.1002/anie.201305464,2013-08-22,0.6254962686035802
Journal of the American Chemical Society,"Total Synthesis and Structure Revision of (−)-Illisimonin A, a Neuroprotective Sesquiterpenoid from the Fruits of <i>Illicium simonsii</i>","Illisimonin A was isolated from Illicium simonsii and has a previously unreported tricyclic carbon framework. It displayed neuroprotective effects against oxygen-glucose deprivation-induced cell injury in SH-SY5Y cells. It incorporates a highly strained trans-pentalene ring system. We report the first synthesis of (±)-illisimonin A. Notable steps in the route include a 1,3-dioxa-2-silacyclohexene templated Diels–Alder cycloaddition and type-3 semipinacol rearrangement to generate the trans-pentalene. The final step is an iron-catalyzed C–H oxidation. The synthetic route is robust, with 94 mg of racemic material prepared in a single pass. Resolving an intermediate enabled the synthesis of natural (−)-illisimonin A. The absolute configuration of (−)-illisimonin A was revised to 1 S,4 S,5 S,6 S,7 R,9 R,10 R based on the X-ray structure of a heavy-atom analogue.",10.1021/jacs.9b05065,2019-08-13,0.6254940124434488
Organic Letters,Total Synthesis of the Terpenoid Buddledone A: 11-Membered Ring-Closing Metathesis,The first total synthesis of buddledone A was accomplished in seven steps from methyl ethyl ketone (MEK). The key step in the sequence featured an 11-membered ring formation by ring-closing metathesis.,10.1021/ol300400x,2012-03-20,0.6254895073212031
Angewandte Chemie International Edition,Total Synthesis of Tiacumicin B: Implementing Hydrogen Bond Directed Acceptor Delivery for Highly Selective β‐Glycosylations,"A total synthesis of tiacumicin B, a natural macrolide whose remarkable antibiotic properties are used to treat severe intestinal infections, is reported. The strategy is in part based on the prior synthesis of the tiacumicin B aglycone, and on the decisive use of sulfoxides as anomeric leaving groups in hydrogen-bond-mediated aglycone delivery (HAD). This new HAD variant permitted highly β-selective rhamnosylation and noviosylation. To increase convergence, the rhamnosylated C1-C3 fragment thus obtained was anchored to the C4-C19 aglycone fragment by adapting the Suzuki-Miyaura cross-coupling used for the aglycone synthesis. Ring-size-selective macrolactonization provided a compound engaged directly in the noviolysation step with virtually total β selectivity. The final efficient removal of all the protecting groups provided synthetic tiacumicin B.",10.1002/anie.202000231,2020-01-31,0.6254871594142797
Journal of Organic Chemistry,"Regioselective Palladium Cross-Coupling of 2,4-Dihalooxazoles:  Convergent Synthesis of Trisoxazoles","A regioselective Suzuki-Miyaura cross-coupling of 2,4-dihalooxazoles followed by a Stille coupling has been successfully developed. The procedure affords convergent syntheses of trisoxazoles in high yield and in a minimum number of steps.",10.1021/jo800121y,2008-03-12,0.625486524050842
European Journal of Organic Chemistry,Efficient Asymmetric Synthesis of an A‐Ring Synthon for Pd‐Catalyzed Preparation of 1α‐Hydroxyvitamin D Metabolites and Analogs,"Abstract The secondary parallel hypercalcemic effects associated with the treatment of several hyperproliferative diseases with the natural hormone 1α,25‐dihydroxyvitamin D 3 (calcitriol) and/or known active vitamin D metabolites and analogs, demand the development of efficient and rapid methods for the preparation of vitamin D receptor (VDR) ligands as new selective and non‐calcemic agonists. Here we describe an efficient and adaptable multigram‐scale synthetic sequence to access an A‐ring synthon as useful precursor of the vitamin D triene system of 1α‐hydroxylated vitamin D derivatives via Pd‐catalyzed carbocyclization/Suzuki–Miyaura cross‐coupling reactions in a protic medium. The key step is an asymmetric Lewis acid‐promoted carbonyl‐ene reaction to a chiral glyosylate ester to establish the 1α‐hydroxyl group of 1α,25‐dihydroxyvitamin D 3 and its derivatives.",10.1002/ejoc.202200314,2022-05-04,0.6254724508640522
Organic Letters,"A Route to the C,D,E Ring System of the<i>Aspidosperma</i>Alkaloids","A short synthetic sequence leading to the formation of the C,D,E-ring subunit of the Aspidosperma alkaloids is reported. This route is based on a ring fragmentation/intramolecular azomethine ylide 1,3-dipolar cycloaddition reaction sequence that gives the desired tricyclic product as a single diastereomer. A γ-amino-β-hydroxy-α-diazo carbonyl compound is shown to fragment in the presence of a Lewis acid to give an iminium product that can be directly reduced to the corresponding amine.",10.1021/acs.orglett.6b01674,2016-08-08,0.6254702985203188
Tetrahedron,"An efficient and facile three-step synthesis of 5-amino-5-deoxy-D-pentonolactams from unprotected D-pentono-1,4-lactones.",,10.1016/s0040-4039(97)10065-x,1997-11-01,0.6254630675310476
Organic Process Research & Development,Large-Scale Synthesis of the Anti-Cancer Marine Natural Product (+)-Discodermolide. Part 5:  Linkage of Fragments C<sub>1</sub><sub>-</sub><sub>6</sub> and C<sub>7</sub><sub>-</sub><sub>24</sub> and Finale,"The finale of the large-scale preparation of 60 g of the highly complex marine natural product, (+)-discodermolide ( 1 ), using a hybridized Novartis−Smith−Paterson synthetic route is presented. This contribution, which is the concluding part of a five-part series, highlights a reagent-controlled stereoselective boron enolate aldol reaction between 2 and 3 forming the C7 hydroxyl-bearing stereocenter, selective reduction of 4a to generate the 1,3- anti -diol 5, and a global deprotection and concomitant lactonization leading to (+)-discodermolide ( 1 ). A novel procedure for converting the minor epimeric aldol adduct 4b into discodermolide using a five-step sequence is also described. This large-scale synthesis of discodermolide involved 39 steps (26 steps in the longest linear sequence) and several chromatographic purifications and delivered sufficient material for early-stage human clinical trials.",10.1021/op034134j,2003-12-04,0.6254462124936854
Tetrahedron,Stereoselective synthesis of a candoxatril intermediate asymmetric hydrogenation,,10.1016/s0040-4039(98)02687-2,1999-03-01,0.6254384187182133
Synlett,"Efficient Synthesis of (+)-Kalafungin and (-)-Nanaomycin D by Asymmetric Dihydroxylation, Oxa-Pictet-Spengler Cyclization, and H<sub>2</sub>SO<sub>4</sub>-Mediated Isomerization","The pyranonaphthoquinone antibiotics and antitumor agents (+)-kalafungin (1) and (-)-nanaomycin D (3 = ent-1) were synthesized from 1,5-napthalenediol (13) in 11 steps. Stereocontrol was high: 99.5 ee/93% diastereoselectivity for 1, 98.5% ee/94% ­diastereoselectivity for 3. Enantiocontrol was achieved by the asymmetric dihydroxylation of the β,γ-unsaturated ester 9. Dia­stereocontrol was realized in the final step by an almost complete epimerization in H2SO4.",10.1055/s-2005-868505,2005-05-03,0.6254342777517443
Synlett,"N-Tosyl-1,2,3-triazoles as Scaffolds for Morpholines: The Total Synthesis of (–)-Chelonin A","Abstract Substituted morpholine derivatives appear frequently in biologically active compounds and thus novel routes towards such structures are of great synthetic interest. Herein, we report the total syntheses of chelonin A, a morpholine-derived marine natural product with reported antibacterial and anti-inflammatory activity. The key step in this process was a rhodium carbenoid 1,3-insertion into a bromohydrin O–H bond, followed by annulation, leading to a 2,6-disubstituted-3,4-dihydro-2H-1,4-oxazine core. This work was then extended to deliver the first asymmetric total synthesis of (–)-chelonin A using an enantioenriched bromohydrin, prepared in turn via asymmetric transfer hydrogenation of an α-bromoketone.",10.1055/a-1982-5433,2022-11-18,0.6254251960157038
Organic Process Research & Development,"An Efficient and Economical Synthesis of 5,6-Diethyl-2,3-dihydro-1<i>H</i>-inden-2-amine Hydrochloride","An efficient and economical synthesis of 5,6-diethyl-2,3-dihydro-1 H -inden-2-amine hydrochloride ( 1 ) utilizing 2-aminoindan as a cheap and commercially readily available starting material is described. The newly developed synthesis involves six-steps with 49% overall yield, and it introduces two ethyl groups at the 5- and 6-positions via sequential regioselective Friedel−Crafts acetylations and hydrogenations of N -protected-2-aminoindan. The Friedel−Crafts acetylations can be carried out neat with high regioselectivity using acetyl chloride as the reagent as well as the solvent, thus avoiding the use of halogenated solvents.",10.1021/op0502093,2005-12-14,0.6254101012442288
Organic Letters,Convergent Synthesis of Fostriecin via Selective Alkene Couplings and Regioselective Asymmetric Dihydroxylation,"A highly convergent synthesis of fostriecin is described, featuring sequential palladium-catalyzed Negishi cross couplings to form the C7-C8 bond and C8-methyl bond, followed by late-stage regio- and stereoselective dihydroxylation of C8-C9.",10.1021/ol902365n,2009-11-10,0.6254085967535034
Organic Letters,Stereocontrolled Total Synthesis of (−)-Isocelorbicol and Its Elaboration to Natural Dihydro-β-agarofuran Esters,"The first total synthesis of four naturally occurring dihydro-β-agarofuran esters has been accomplished via a highly stereocontrolled 14-step access to their common core triol, (-)-isocelorbicol. A semipinacol rearrangement of an epoxy alcohol to install a quaternary carbon, diastereoselective conjugate reduction of a spirocyclic butenolide for the establishment of a methyl-bearing chiral center, and ring-closing metathesis to construct the decalin ring system were exploited as the key steps for the high-yielding synthesis of (-)-isocelorbicol.",10.1021/acs.orglett.0c03419,2020-11-23,0.6254060183756951
Organic Process Research & Development,Metal-Catalyzed C–N Bond Forming Reaction Selection and Process Development for the Manufacture of AZD7594,Process development activities required to develop a robust and scalable synthetic route to AZD7594 ( 1 ) are disclosed. Included in this paper is the rationale for the selection of a palladium-mediated Buchwald–Hartwig coupling to form a key C–N bond. Reaction optimization and understanding were performed to minimize impurity formation and to develop a robust control strategy. The optimized synthetic sequence was used to manufacture 220 kg of AZD7594 ( 1 ) for clinical trials.,10.1021/acs.oprd.3c00393,2024-01-31,0.6254060122728509
Tetrahedron,Reactions of 2-acylbenzoates with dimethyloxosulphonium methylide: A novel route to isocoumarins,,10.1016/s0040-4039(01)81355-1,1984-01-01,0.6253973345702085
Journal of the American Chemical Society,"General Approach for the Synthesis of Ajmaline/Sarpagine Indole Alkaloids:  Enantiospecific Total Synthesis of (+)-Ajmaline, Alkaloid G, and Norsuaveoline via the Asymmetric Pictet−Spengler Reaction","A general approach (oxyanion-Cope strategy) for the synthesis of sarpagine/ajmaline indole alkaloids has been developed. (+)-Ajmaline 1 and alkaloid G 2 as well as norsuaveoline 3 have been synthesized from d -(+)-tryptophan in enantiospecific fashion via the asymmetric Pictet−Spengler reaction and a stereocontrolled oxyanion-Cope rearrangement as key steps. The synthesis of these indole alkaloids employed a stereospecific Pictet−Spengler/Dieckmann protocol to prepare the key intermediate, (−)- N b -benzyl tetracyclic ketone ( 7a or 7b ). This ketone was converted into α,β-unsaturated aldehyde ( 8a or 8b ) and further transformed into (+)-ajmaline 1 and alkaloid G 2 as well as norsuaveoline 3 . It was also found that reduction of 29 can be done stereospecifically to form the 2-epidiacetylajmaline derivative 30 which has the same configuration at C(2) as that of quebrachidine and of the bisindole alstonisidine. The ring closure reaction (from 27 to 28 ) to form the sarpagine skeleton was completed in 91% yield. It should now be possible to prepare the antipode of (+)-ajmaline via this approach for biological screening.",10.1021/ja990184l,1999-07-16,0.6253933736948618
Tetrahedron,"An alternative route for the preparation of α,α-difluoropropargylphosphonates",,10.1016/s0040-4039(00)01354-x,2000-10-01,0.6253885203208646
Organic Letters,Stereoselective Synthesis of a Dioxa-bicyclo[3.2.1]octane SGLT2 Inhibitor,"A promising class of SGLT2 inhibitors bearing a unique dioxa-bicyclo[3.2.1]octane motif was recently disclosed. An improved stereoselective synthesis providing efficient access to one of the most potent and selective compounds from this class is reported. A one-pot deprotection/cyclization was used as the key step to form the dioxa-bicyclo[3.2.1]octane motif with full control of stereochemistry. Using an appropriately substituted aryl group, the route enables the synthesis of any given compound from the class.",10.1021/ol100940w,2010-06-08,0.6253875812207731
Journal of the American Chemical Society,The Total Synthesis of (+)-Dragmacidin F,"The first total synthesis of (+)-dragmacidin F has been accomplished, establishing the absolute configuration of this biologically important, antiviral marine alkaloid. The convergent route described features a palladium-mediated oxidative pyrrole carbocylization reaction to construct the [3.3.1] bicycle, as well as a highly selective Suzuki coupling to build the carbon skeleton of the natural product. A late-stage Neber rearrangement allows for the facile installation of the aminoimidazole moiety to provide (+)-dragmacidin F.",10.1021/ja046695b,2004-07-20,0.6253687144580651
Organic Process Research & Development,"The Synthesis of the High-Potency Sweetener, NC-00637. Part 3:  The Glutamyl Moiety and Coupling Reactions","The synthesis of the high-potency sweetener, NC-00637 ( 1 ), required selective preparation of the γ-protected glutamic acid. Coupling of the three components could be performed in any order, but the final route involved N -acylation of the protected l -glutamic acid with the acid chloride derived from ( S )-2-methylhexanoic acid. Activation of the α-carboxyl group allowed condensation with 5-amino-2-cyanopyridine ( 4 ). Saponification of the γ-ester 19 then provided the sweetener 1 .",10.1021/op0341115,2003-12-04,0.6253602465540566
Organic Process Research & Development,Development of a Scalable Synthesis of Oxadiazole Based S1P<sub>1</sub> Receptor Agonists,A robust and scalable synthesis was developed for the preparation of oxadiazole based S1P 1 inhibitors. A new method for the separation of triphenylphosphine oxide from reaction products and an improved method for the synthesis of oxadiazoles in the presence of DBU were incorporated into the process to achieve its scalability.,10.1021/op300345v,2013-04-02,0.6253374392548019
Synlett,"A Facile and Efficient Synthesis of 4,5-Dihydro-1H-2,5-benzoxazocine-1,6(3H)-diones from 1,2-Cyclic Sulfamidates","4,5-Dihydro-1 H -2,5-benzoxazocine-1,6(3 H )-diones have been synthesized by treatment of tert -butoxycarbonyl (Boc)-protected 1,2-cyclic sulfamidates with phthalic acid derivatives. Protection of one acid hydroxy group and the deprotection of the N -Boc group of the adducts, followed by cyclization, afforded the desired products in high yields. When derivatives of isophthalic acid were used in the synthetic sequence, nine-membered-ring analogues were formed. All the prepared compounds except one are novel.",10.1055/s-0035-1561203,2016-01-21,0.6253120371501619
Organic Letters,Synthesis of Novel Azaspiro[3.4]octanes as Multifunctional Modules in Drug Discovery,Step-economic and scalable syntheses of novel thia-azaspiro[3.4]octanes are reported. These spirocycles and some related intermediates can serve as uncharted multifunctional modules for drug discovery chemistry.,10.1021/ol2025313,2011-10-18,0.6253053017050781
Journal of the American Chemical Society,Total Synthesis of Hypersampsone M,"We report the first total synthesis of hypersampsone M, an archetypal member of the homoadamantane polycyclic polyprenylated acylphloroglucinols (PPAPs). Commencing from cyclohexenone, a key cyclopentene annulation followed by ring-expansion results in an elusive hydrazulene that undergoes a series of unexpected late-stage transformations, ultimately enabling completion of the synthesis. The route detailed herein represents a potentially general strategy for the synthesis of related homoadamantane PPAPs.",10.1021/jacs.4c07007,2024-07-03,0.6252900505867284
Synlett,A Concise Synthesis of Fumagillol,"All articles of this category A concise synthesis of fumagillol was accomplished in twelve steps starting from cyclohexadiene, proceeding by way of ring-opening of a symmetrical protected epoxydiol with a cuprate reagent and subsequent protecting group manipulation to give a key ketone intermediate. Installation of the required epoxide functions was achieved by addition of chloromethyllithium to the ketone and by directed epoxidation of the unsaturated side-chain. fumagillol - stereoselective synthesis - epoxides - cuprate",10.1055/s-2001-13359,2001-12-31,0.6252891613887598
Organic Letters,Asymmetric Total Synthesis of (+)-Lemnardosinane A,"The asymmetric total synthesis of (+)-lemnardosinane A, a rare rearranged sesquiterpenoid, has been accomplished from ( S )-carvone. Key features of the synthesis are the formation of a bicyclo[3.3.1]nonane skeleton using the intramolecular aldol reaction, the stereoselective introduction of an alkyne group, and the stereoselective formation of a tricyclic skeleton via intramolecular pinacol coupling.",10.1021/acs.orglett.4c01384,2024-06-07,0.625276216851595
European Journal of Organic Chemistry,"Synthesis of Pyranocyclopentaindolines Representing the Western Sections of Janthitrem B, JBIR‐137, and Shearinine G","Abstract The synthesis of the ABCD tetracyclic partial structures of the fungal indole diterpenes janthitrem B, JBIR‐137, and shearinine G is reported. The route starts from 5‐formylated indoline that is coupled to a dihydropyran moiety, followed by Prins cyclization. A diene was obtained that was oxygenated in a divergent manner. The hydroxylated tetracyclic western half of janthitrem B was obtained in eight steps and 10 % overall yield. We also share our experience with alternative approaches passing via alkynylated precursors. This includes the gold‐catalyzed cycloisomerization of a 6‐ethynyl‐5‐prenylindoline.",10.1002/ejoc.202101454,2022-01-04,0.625275904195617
Organic Letters,"Diastereoselective Synthesis of an Advanced Intermediate of Thapsigargin and Other 6,12-Guaianolides Using a RCEYM Strategy","A new and flexible approach toward the synthesis of 6,12-guaianolide anticancer drugs such as trilobolides or thapsigargin has been developed that could be applied to the preparation of analogues with a modified ring system. The synthesis starts from commercial 2-methylcyclopentane-1,3-dione, only relying on diastereoselective reactions for the construction of the stereogenic centers at C1, C3, C6, and C10 and features a high-yielding ring-closing enyne metathesis (RCEYM) step for the formation of the [5,7] bicyclic core.",10.1021/acs.orglett.8b00456,2018-04-04,0.6252668294451263
Chemical Science,Cyclodepsipeptide alveolaride C: total synthesis and structural assignment,"First stereoselective total synthesis of naturally occurring bioactive cyclodepsipeptide alveolaride C has been achieved using a convergent approach. This synthetic study enabled us to establish unambiguously the stereochemistry of three unassigned chiral centres embedded in the nonpeptidic segment as well as revised the stereochemistry of the proposed β-phenylalanine counterpart of the molecule. The key strategic features of this synthesis include Sharpless asymmetric dihydroxylation for installing the vicinal diol moiety, Julia-Kocienski olefination for constructing the aliphatic side chain, the Shiina protocol for intermolecular esterification, amide coupling and macrolactamization for the ring formation.",10.1039/d0sc04478d,2020-01-01,0.6252633384995645
Synthesis,"A General Approach to the Asymmetric Synthesis of Lignans: (-)-Methyl Piperitol, (-)-Sesamin, (-)-Aschantin, (+)-Yatein, (+)-Dihydroclusin, (+)-Burseran, and (-)-Isostegane","A highly efficient, diastereo- and enantioselective route was developed to access a great variety of lignans. The asymmetric synthesis of the 2,3-disubstituted γ-butyrolactones 9a-c could be improved in the case of aldol reactions by employing 2.2 equivalents of LiCl as an additive to provide, after purification, highly diastereo- and enantioenriched starting materials for the synthesis of the furofuran lignans (-)-methyl piperitol, (-)-sesamin, and (-)-aschantin. Furthermore, the γ-butyrolactone 15 was converted into dibenzylbutyrolactone lignan (+)-yatein, the dibenzylbutandiol type (+)-dihydroclusin, the tetrahydrofuran type (+)-burseran, and the dibenzocyclooctadiene type (-)-isostegane.",10.1055/s-2002-20967,2002-01-01,0.6252538409450068
Organic Process Research & Development,Exemplifying Prediction of Preferred Coupling Partners in Developing a Buchwald–Hartwig Coupling for the Synthesis of a c-Kit Inhibitor,Two convergent syntheses for compound 1 are described that apply Buchwald–Hartwig coupling as the key step. This development work provides a direct comparison of the coupling results from different coupling partners and illustrates that more efficiency can be achieved by selecting the right coupling partners.,10.1021/acs.oprd.8b00043,2018-03-28,0.6252238672278367
Organic Process Research & Development,Development of a Manufacturing Process for an HCV Protease Inhibitor Candidate Molecule,"The scale-up of a prototype HCV protease inhibitor ( 1 ) from gram scale in the laboratory to kilogram scale in the pilot plant is described. Key features of the optimization included the synthesis of bulk quantities of exomethylene proline intermediate 6, separation of the diastereomers of spirocycle 2 without chromatography, isolation of the precursor to 1 to purge byproducts that might raise genotoxic structural alerts, and purification of an amorphous drug substance via a crystalline acetic acid solvate.",10.1021/op500210w,2014-12-14,0.6252076064861901
Organic Letters,Asymmetric Syntheses of (−)-1-Deoxymannojirimycin and (+)-1-Deoxyallonojirimycin via a Ring-Expansion Approach,"The asymmetric syntheses of (-)-1-deoxymannojirimycin and (+)-1-deoxyallonojirimycin are described herein. The ring-closing iodoamination of two epimeric bishomoallylic amines to give the corresponding 5-iodomethylpyrrolidines was followed by in situ ring-expansion to give two diastereoisomerically pure (>99:1 dr) cyclic carbonates. Subsequent deprotection gave (-)-1-deoxymannojirimycin and (+)-1-deoxyallonojirimycin as single diastereoisomers in 7.4 and 3.3% overall yield, respectively, from commercially available starting materials.",10.1021/ol400735z,2013-04-09,0.6252014323402567
Tetrahedron,The chemistry of vicinal tricarbonyls. an efficient synthesis of (±)-vasicine,,10.1016/0040-4039(91)85059-e,1991-11-01,0.6251964146737585
Synthesis,"Synthesis of Rofecoxib, (MK 0966, Vioxx® 4-(4′-Methylsulfonylphenyl)-3-Phenyl-2(5H)-Furanone), a Selective and Orally Active Inhibitor of Cyclooxygenase-2","The synthesis of Vioxx® (Rofecoxib, MK 966, 4-(4’methylsulfonylphenyl)-3-phenyl-2(5H)-furanone), a newly FDA approved inhibitor of cyclooxygenase-2, is described.",10.1055/s-2001-17519,2001-01-01,0.6251928481985092
Journal of Organic Chemistry,"An Asymmetric Synthesis of (2<i>S</i>,5<i>S</i>)-5-Substituted Azepane-2-Carboxylate Derivatives","To facilitate a drug discovery project, we needed to develop a robust asymmetric synthesis of (2S,5S)-5-substituted-azepane-2-carboxylate derivatives. Two key requirements for the synthesis were flexibility for elaboration at C5 and suitability for large scale preparation. To this end we have successfully developed a scalable asymmetric synthesis of these derivatives that starts with known hydroxy-ketone 8. The key step features an oxidative cleavage of aza-bicyclo[3.2.2]nonene 14, which simultaneously generates the C2 and C5 substituents in a stereoselective manner.",10.1021/jo102475s,2011-01-28,0.6251833349986403
Journal of Organic Chemistry,"Development of a Highly β-Selective Ribosylation Reaction without Using Neighboring Group Participation:  Total Synthesis of (+)-Caprazol, a Core Structure of Caprazamycins","Full details of the total synthesis of (+)-caprazol are described. The key elements of our approach include the early stage introduction of the aminoribose in a highly beta-selective manner, using the steric hindrance in the transition state and the construction of the diazepanone by a modified intramolecular reductive amination. The 5'-C-glycyluridine derivative 9, which was prepared stereoselectively via Sharpless asymmetric aminohydroxylation, was ribosylated with 2,3-O-alkylidene ribofuranosyl donors. It was revealed that increasing the size of the alkyl substituents of the acetal unit resulted in improving the stereoselectivity of the anomeric position, and the desired ribosides 21b (1' '-beta) and 22b (1' '-alpha) were obtained in 80% yield (21b/22b = 24.0/1) when the ribosyl fluoride 16 possessing a more sterically hindered 3-pentylidene group was used. The origin of the stereoselectivity of the ribosylation was also discussed. Construction of the diazepanone system was optimized with the model aldehyde 37, and the desired diazepanone 38 was obtained in 88% yield via two-step reaction sequence including catalytic hydrogenation followed by hydride reduction. Application of this method to the aldehyde 44 successfully afforded the diazepanone derivatives 45 and 46, functional group manipulation of which completed the total synthesis of (+)-caprazol.",10.1021/jo701699h,2007-11-21,0.625178050931469
Journal of Organic Chemistry,"Stereoselective Synthesis of HIV-1 Protease Inhibitor, DMP 323","DMP 323, a potent HIV-1 protease inhibitor, has been synthesized by an efficient stereoselective process, amenable to large scale preparations. The core C(2) symmetric diol was synthesized by a stereoselective pinacol coupling of CBZ protected D-phenylalanine. Judicious selection of protecting groups allowed cyclic urea formation under mild conditions, enhanced the ease of bis-alkylation, and led to intermediates which were easily purified without chromatography. Additionally, a one-pot, high yield process was developed to prepare the alkylating agent, 4-[(triphenylmethoxy)methyl]benzyl chloride from 1,4-benzenedimethanol.",10.1021/jo951847u,1996-01-01,0.6251740000876737
Tetrahedron,A novel and convenient route to L-homoserine lactones and L-phosphinothricin from L-aspartic acid,,10.1016/s0040-4039(00)79053-8,1992-05-01,0.6251690366603014
Angewandte Chemie International Edition,Enantioselective Polyene Cyclization Catalyzed by a Chiral Brønsted Acid,"The first enantioselective polyene cyclization initiated by a BINOL-derived chiral N-phosphoramide (NPA) catalyzed protonation of an imine is described. The ion-pair formed between the iminium ion and chiral counter anion of the NPA plays an important role for controlling the stereochemistry of the overall transformation. This strategy offers a highly efficient approach to fused tricyclic frameworks containing three contiguous stereocenters, which are widely found in natural products. In addition, the first catalytic asymmetric total synthesis of (-)-ferruginol was accomplished with an NPA catalyzed enantioselective polyene cyclization, as the key step for the construction of the tricyclic core, with excellent yield and enantioselectivity.",10.1002/anie.201711603,2018-01-10,0.6251653890184337
Tetrahedron,"A versatile synthetic route to 11H-indolo[3,2-c]isoquinolines",,10.1016/j.tetlet.2009.07.107,2009-07-25,0.625161973578239
Tetrahedron,"A versatile synthetic route to indolizidines, (+)-7-deoxy-6-epicastanospermine, (−)-7,8-dideoxy-6-epicastanospermine and (−)-N-acetylslaframine",,10.1016/s0040-4039(98)02051-6,1998-12-01,0.625161973578239
Tetrahedron,A novel cyclotetrapeptide produced by Lactobacillus helveticus as a tyrosinase inhibitor,,10.1016/s0040-4039(00)79177-5,1993-05-01,0.6251535019137722
Tetrahedron,"Xantholipin, a novel inhibitor of HSP47 gene expression produced by Streptomyces sp.",,10.1016/s0040-4039(03)01318-2,2003-06-30,0.6251535019137722
Tetrahedron,Total synthesis of (+)-varitriol via a symmetrical furanose diol as the key intermediate,,10.1016/j.tetlet.2011.10.076,2011-11-14,0.6251493042404692
Journal of Organic Chemistry,The First Asymmetric Total Syntheses and Determination of Absolute Configurations of Xestodecalactones B and C,"The first efficient asymmetric total syntheses of xestodecalactones B and C have been accomplished in 10 steps with an overall yield of 22 and 20.2%, respectively. The key steps involve the utility of Evans oxazolidinone-mediated syn-aldol condensations to establish the C-9 configuration and the macrolide ring formation by intramolecular acylation. The absolute configurations of xestodecalactones B and C have been determined via these syntheses.",10.1021/jo070159v,2007-03-01,0.6251440758099183
Angewandte Chemie International Edition,Total Synthesis of Efomycine M,Two-directional synthesis: Key steps in the first total synthesis of the anti-inflammatory agent efomycine M (1) are a two-directional C11–C12 chain elongation and an early-stage dimerization reaction. The central stereopentad is synthesized by a highly stereoselective sequence consisting of an anti-aldol reaction and a diastereoselective reduction.,10.1002/anie.200701065,2007-06-26,0.6251431112380482
Journal of Organic Chemistry,A Novel Efficient Synthesis of Dihydroxyacetone Phosphate and Bromoacetol Phosphate for Use in Enzymatic Aldol Syntheses,"Dihydroxyacetone phosphate (DHAP, 7 ) and bromoacetol phosphate (BAP, 6 ) were synthesized in four and five steps, respectively, starting from 1,3-dibromoacetone ( 2 ). The key step involves desymetrization and ketone protection of 2 to prepare alcohol 3 . Phosphorylation of 3 followed by hydrogenolysis and then deprotection of the ketal function afforded 6 . A solution of 7 was prepared after treatment of 6 with NaOH. This original route allows a short and convenient preparation of DHAP in large scale and high purity for application to the synthesis of sugar derivatives and preparation of BAP for triosephosphate isomerase inhibition.",10.1021/jo970565m,1997-08-01,0.6251373888560229
Angewandte Chemie International Edition,Total Synthesis of Haliclonin A,"The total synthesis of haliclonin A was accomplished. Starting from 3,5-dimethoxybenzoic acid, a functionalized cyclohexanone fused to a 17-membered ring was prepared through a Birch reduction/alkylation sequence, ring-closing metathesis, intramolecular cyclopropanation, and stereoselective 1,4-addition of an organocopper reagent to an enone moiety. Reductive C-N bond formation via an N,O-acetal forged the 3-azabicyclo[3.3.1]nonane core. The allyl alcohol moiety was constructed by a sequence involving stereoselective α-selenylation of an aldehyde via an enamine, syn-elimination of a selenoxide, and allylation of the aldehyde with an allylboronate. Formation of the 15-membered ring containing a skipped diene was achieved by ring-closing metathesis, and final transformations led to the synthesis of haliclonin A.",10.1002/anie.202016343,2021-02-09,0.6251350710543706
Tetrahedron,An efficient route to 3-substituted cyclobutanone derivatives,,10.1016/s0040-4039(03)00081-9,2003-02-01,0.6251319022019073
Tetrahedron,Enantioselective synthesis of a new fluoro-substituted HMG-COA reductase inhibitor,,10.1016/s0040-4039(01)93462-8,1989-01-01,0.6251286228182259
Synthesis,"Ein neues Verfahren zur Herstellung von 6-Methyl-1,2,3-oxathiazin-4(3<i>H</i>)-on-2,2-dioxid Kaliumsalz (Acesulfam-K)","All articles of this category A New Method for the Preparation of 6-Methyl-1,2,3-oxathiazine-4(3 H )-one 2,2-Dioxide, Potassium Salt (Acesulfame K) A simple two-step synthesis of the title compound, an artificial sweetener, starting from amidosulfonic acid and diketene is described.",10.1055/s-1990-26888,1990-01-01,0.6251167840393987
Organic Letters,Total Synthesis of Brasilicardins A and C,"The first total synthesis of brasilicardins A and C, novel diterpenoid-saccharide-amino acid hybrid metabolites with unique immunosuppressive activity, is described. The key step is a Diels-Alder/reductive angular methylation sequence capitalizing on a trans-fused bicyclic α-cyano-α,β-enone as its precursor to construct the 8,10-dimethyl-trans/syn/trans-perhydrophenanthrene skeleton. Other notable features include an anti-selective aldol reaction, a stereocontrolled glycosylation of a C2 alcohol, and a one-pot, two-step global deprotection sequence that did not damage these sensitive molecules.",10.1021/acs.orglett.7b02728,2017-10-04,0.625108930415538
Organic Process Research & Development,"Synthetic Route Design of AZD4635, an A<sub>2A</sub>R Antagonist","The AstraZeneca approach to synthetic Route Design is exemplified through our AZD4635 chemical development program. The identification of possible new route concepts is presented, as well as their subsequent prioritization for practical exploration based on project objectives. Selected ideas were tested to demonstrate proof of concept for the bond formation strategy and, where successful, were fed into a decision tool based on key SELECTion principles.",10.1021/acs.oprd.9b00171,2019-06-25,0.6251026155087035
European Journal of Organic Chemistry,"A New Route to 2,7- and 7-Functionalized Labdanes","A new route for the synthesis of 2,7- and 7-functionalized labdanes starts from (R)-carvone (1). 11-Nordrim-7-en-9-one (15) is an appropriate starting material for the total synthesis of hispanone (21), a biologically active furolabdane isolated from the Mediterranean medicinal plant Ballota saxatilis.",10.1002/(sici)1099-0690(200004)2000:8<1609::aid-ejoc1609>3.0.co;2-2,2000-04-01,0.6251007140639515
Angewandte Chemie International Edition,Biomimetic Synthesis of the Calcineurin Phosphatase Inhibitor Dibefurin,"Dibefurin is a Ci -symmetric natural product that acts as an inhibitor of calcineurin phosphatase. A six-step synthesis of this compound is reported, which features an oxidative dimerization of the aromatic polyketide epicoccine as the key step. Dibefurin is proposed to be related to epicolactone, a complex yet racemic fungal metabolite that has recently been discovered. Attempts to access epicolactone from epicoccine and epicoccone B resulted in an unusual dimer that is formed through a hetero-Diels-Alder reaction of a para-quinone methide with an ortho-quinone.",10.1002/anie.201407088,2014-11-04,0.6250863126340224
Tetrahedron,Synthesis of 11β-hydroxy-18-ethynylprogesterone: an inhibitor of aldosterone biosynthesis,,10.1016/s0040-4039(00)98416-8,1985-01-01,0.6250790086646522
Synthesis,Practical Syntheses of Enantiomerically Pure Key Intermediates of Opioid Receptor-like 1 (ORL1) Antagonists,"Practical syntheses of enantiomerically pure key intermediates of opioid receptor-like 1 (ORL1) antagonists are described. Our synthetic methodology features the preparation of multigram quantities of seven-membered key intermediate (-)-3 and six-membered one (-)-4 without the use of toxic tin reagents. In the case of (-)-3, the key step involved diastereoselective reduction using a sterically hindered reducing reagent. Our methodology allows for facile scale-up to afford the products in multigram quantities [in the case of (-)-4, >100-g quantities). These convenient approaches facilitate structure-activity relationship studies including in vivo cardiovascular adverse effects.",10.1055/s-0028-1087989,2009-03-06,0.6250736297651495
Synlett,Addition of 2-Lithiothiazoles to ROPHy/SOPHy Aldoximes: Asymmetric Synthesis of 1-(2-Thiazolyl)ethylamines,All articles of this category A new asymmetric synthesis of 1-(2-thiazolyl)ethylamines is described in which the key step is the diastereoselective addition of 2-lithiothiazoles to O -(1-phenylbutyl) aldoximes. oxime ether - hydroxylamine - thiazole,10.1055/s-1999-3109,1999-12-31,0.6250610683156025
Synthesis,Stereoselective Total Synthesis of Pectinolide H,"An efficient total synthesis of pectinolide H was achieved by using alkynylation, asymmetric reduction in the presence of a Corey–Bakshi–Shibata catalyst, and a Still–Gennari olefination as key steps.",10.1055/s-0032-1318000,2013-01-18,0.6250507195992441
Journal of the American Chemical Society,Concise Synthesis of (−)-Cycloclavine and (−)-5-<i>epi</i>-Cycloclavine via Asymmetric C–C Activation,"To illustrate the synthetic significance of C-C activation methods, here we describe an efficient strategy for the enantioselective total syntheses of (-)-cycloclavine and (-)-5- epi-cycloclavine, which is enabled by an asymmetric Rh-catalyzed ""cut-and-sew"" transformation between benzocyclobutenones and olefins. Despite the compact structure of cycloclavine with five-fused rings, the total synthesis was accomplished in 10 steps with a 30% overall yield. Key features of the synthesis include (1) a Pd-catalyzed tandem C-N bond coupling/allylic alkylation sequence to construct the nitrogen-tethered benzocyclobutenone, (2) a highly enantioselective Rh-catalyzed carboacylation of alkenes to forge the indoline-fused tricyclic structure, and (3) a diastereoselective cyclopropanation for preparing the tetrasubstituted cyclopropane ring. Notably, an improved catalytic condition has been developed for the nitrogen-tethered cut-and-sew transformation, which uses a low catalyst loading and allows for a broad substrate scope with high enantioselectivity (94-99% e.e.). The C-C activation-based strategy employed here is anticipated to have further implications for syntheses of other natural products that contain complex fused or bridged rings.",10.1021/jacs.8b05549,2018-07-06,0.6250484675285656
Synlett,The Development of a Direct Synthetic Route to Pleurotin,"All articles of this category An intermediate (6-hydroxy-7,10-dimethoxy-2a,5,5a,6,10b,10c-hexahydro-2 H -anthra[9,1- bc ]furan-2-one) for the synthesis of pleurotin was prepared from 2,5-dimethoxybenzyl alcohol. The key step was a tandem photoenolization/Diels-Alder reaction.",10.1055/s-1991-20636,1991-01-01,0.6250403103727746
Angewandte Chemie International Edition,Total Synthesis of the Antibiotic Erypoegin H and Cognates by a PtCl<sub>2</sub>‐Catalyzed Cycloisomerization Reaction,"Fighting back: A concise route to the pterocarpene derivative erypoegin H, a natural product endowed with considerable activity against a range of methicillin-resistant Staphyllococcus aureus strains and vancomycin-resistant enterococci, has been developed. The key step in the synthesis is a PtCl2-catalyzed carboalkoxylation reaction of an alkyne (see retrosynthesis; Piv=pivaloyl).",10.1002/anie.200700895,2007-05-10,0.6250327995903623
Angewandte Chemie International Edition,A Concise Ring‐Expansion Route to the Compact Core of Platensimycin,"Oxatropanes from oxiranes: An expedient assembly of the compact platensimycin core is described. The synthetic approach relies on a Suzuki cross-coupling, a late-stage dearomatization reaction, and a copper-catalyzed vinyl oxirane ring expansion for accessing the oxatropane moiety of the natural product.",10.1002/anie.200903347,2009-10-01,0.6250287220144268
Journal of Organic Chemistry,"Synthesis of Dihydroplakortin, 6-<i>epi</i>-Dihydroplakortin, and Their C10-Desethyl Analogues","The first synthesis of the marine endoperoxide 9,10-dihydroplakortin, of its C10-desethyl analogue, and of their corresponding C6 epimers is described. Stereogenic centers at C4 and at the lateral chain have been stereoselectively synthesized through Evans' chiral auxiliary chemistry. Moreover, the reported synthesis features a one-pot three-step hydroperoxysilylation/cyclization reaction for the construction of the endoperoxide ring system. Homologation of the aldehyde resulting from diol cleavage through a Wittig-based strategy gave access to the ester-containing lateral chain at C3.",10.1021/jo1001559,2010-03-03,0.6250280950814361
Tetrahedron,Asymmetric synthesis of a key ring A synthon for 1α-hydroxy-19-nor vitamin D,,10.1016/s0040-4039(98)00682-0,1998-05-01,0.6250021586599654
Tetrahedron,"Photocycloaddition on 2-methyloxazolo[5,4-b]pyridine: a route to the oxazolo[5,4-b]azocine system",,10.1016/0040-4039(96)01225-7,1996-08-01,0.6249991296085576
Tetrahedron,"Asymmetric preparation of 1,2,2,2-tetrafluoroethyl methyl ether, an intermediate in the synthesis of volatile anesthetics",,10.1016/s0040-4039(00)60711-6,1994-06-01,0.6249925266786143
Journal of Organic Chemistry,"A Strategy for the Asymmetric Aminohomologation of α,β-Dihydroxy Aldehydes:  Application to the Synthesis of the Southwest Tripeptide Segment of Echinocandin B","The synthesis of the (2S,3S,4S)-3,4-dihydroxyhomotyrosine amino acid segment, present in echinocandin B, in its activated form ready for peptide coupling is described. The key steps of the approach are the enantioselective AD reaction of 4-methoxycinnamic acid methyl ester, a completely diastereoselective [2 + 2] hydroxyketene-imine cycloaddition, and the TEMPO-assisted cycloexpansion of the resulting 3-hydroxy beta-lactam to the corresponding alpha-amino acid N-carboxy anhydride (NCA). The smooth opening of the latter upon treatment with L-Thr(OSi(t)BuPh(2))OMe and further acylation with the N-Cbz protected L-4-tert-butyldiphenylsilyloxy proline rendered the southwest portion of echinocandin B.",10.1021/jo990964c,1999-12-10,0.6249834657622073
Organic Letters,Expedient Route to the Functionalized Calyciphylline A-Type Skeleton via a Michael Addition–RCM Strategy,"An efficient, robust, and scalable strategy to access the functionalized core of calyciphylline A-type alkaloids has been developed starting from commercially available 3-methylanisole. Key features of this approach are an intramolecular Michael addition/allylation sequence and a ring-closing metathesis step.",10.1021/ol202000w,2011-09-07,0.6249826374980215
Journal of Organic Chemistry,An Enantioselective Approach to Furanoeremophilanes: (+)-9-Oxoeuryopsin,"An enantioselective total synthesis of the furanoeremophilane sesquiterpene (+)-9-oxoeuryopsin 1 is reported. The synthesis involves as a key step a copper(II) triflate catalyzed tandem asymmetric conjugate addition of AlMe3 to 2-methyl-2-cyclohexen-1-one with the Feringa (S,R,R)-phosphoramidite binaphthol ligand, followed by aldol condensation of the resulting aluminum enolate with 4-methyl-3-furaldehyde 4. This tandem transformation has not been previously reported with a 2-substituted-2-cyclohexen-1-one. Conventional functional group manipulations completed the synthesis.",10.1021/jo400399q,2013-05-06,0.6249799996383211
Organic Process Research & Development,Use of a Curtius Rearrangement as Part of the Multikilogram Manufacture of a Pyrazine Building Block,"Commercial route definition for a glucokinase activator called for a reevaluation of the synthesis and processes used to access multikilogram quantities of 2-amino-5-methylpyrazine. After consideration of different options, a variation of the Curtius rearrangement used by the medicinal chemistry route was selected for further development. The formation of an acyl azide for the Curtius rearrangement required a process safety control strategy to be put in place. The process developed was used to successfully deliver multikilogram quantities of 2-amino-5-methylpyrazine in an overall yield of 68%, starting from 5-methylpyrazine-2-carboxylic acid.",10.1021/acs.oprd.7b00340,2017-12-04,0.62496278510184
Journal of Organic Chemistry,Asymmetric Synthesis of Methoxylated Ether Lipids: Total Synthesis of n-3 Polyunsaturated Docosahexaenoic Acid-Like Methoxylated Ether Lipid,"The first total synthesis of a docosahexaenoic acid (DHA)-like methoxylated ether lipid (MEL) is reported. This compound constitutes an all- cis methylene skipped hexaene framework identical to that present in DHA, the well-known omega-3 polyunsaturated fatty acid. The polyene C22 hydrocarbon chain, bearing a methoxyl group in the 2-position and R -configuration at the resulting chiral center, is attached by an ether linkage to the pro-S hydroxymethyl group ( sn -1 position) of a glycerol backbone. The asymmetric synthesis is highly convergent and based on the polyacetylene approach involving iterative copper-promoted coupling reactions of propargyl bromides with terminal alkynes and semihydrogenation of the resulting hexayne. Starting from enantiopure R -solketal and racemic epichlorohydrin, the targeted MEL was accomplished in an 8.2% yield over eight steps (longest linear sequence) involving an enantio- and diastereopure glyceryl glycidyl ether key C6-building blocks from which the polyynes were constructed.",10.1021/acs.joc.2c01991,2022-10-24,0.6249552561072581
Angewandte Chemie International Edition,Synthesis of 3‐Oxaterpenoids and Its Application in the Total Synthesis of (±)‐Moluccanic Acid Methyl Ester,"Cascades: An InBr(3)-catalyzed intermolecular polyene cyclization initiated by a Prins reaction provides a concise approach to 3-oxaterpenoid derivatives. The reaction is compatible with various aldehydes, ketones, and polyolefin-alcohol substrates. In addition, the total synthesis of (±)-moluccanic acid methyl ester was achieved in seven steps by using such a Prins-polyene cyclization as the key step.",10.1002/anie.201205981,2012-09-17,0.6249419440169499
Journal of the American Chemical Society,Evolution of a Total Synthesis of (−)-Kendomycin Exploiting a Petasis−Ferrier Rearrangement/Ring-Closing Olefin Metathesis Strategy,"A convergent stereocontrolled total synthesis of (-)-kendomycin (1) has been achieved. The synthesis proceeds with a longest linear sequence of 21 steps, beginning with commercially available 2,4-dimethoxy-3-methylbenzaldehyde (12). Highlights of the synthesis include an effective Petasis-Ferrier union/rearrangement tactic to construct the sterically encumbered tetrahydropyran ring, a ring-closing metathesis to generate the C(4a-13-20a) macrocycle, an effective epoxidation/deoxygenation sequence to isomerize the C(13,14) olefin, and a biomimetic quinone-methide-lactol assembly to complete the synthesis.",10.1021/ja060369+,2006-03-24,0.6249408639887628
Synthesis,<i>O</i>-Protected <b><i>N</i></b>-(2-Nitrophenylsulfonyl)hydroxylamines: Novel Reagents for the Synthesis of Hydroxamates,Preparative methods for novel O-protected N-(2-nitrophenylsulfonyl)hydroxylamines (8a-e) are described. Their versatility as intermediates en route to polyhydroxamates is exemplified by the synthesis of a non-amide DFO analog 22.,10.1055/s-2001-14567,2002-07-26,0.624935370282491
Organic Letters,A Diverted Total Syntheses of Potent Cell Adhesion Inhibitor Peribysin E Analogues,"Preliminary results from a program aimed at the creation of a focused library of analogues around the natural product peribysin E, a potent biologically active and structurally fascinating molecule, are reported. The total synthesis of (±)-peribysin E was accomplished using a short route. Eight new analogues of the natural compound have been accomplished by means of ""diverted total synthesis"" in less than 10 steps. The present effort highlights protecting-group-free total syntheses and the shortest route to access these functionally embellished hydrindanes.",10.1021/ol400555m,2013-04-04,0.6249346975774566
Journal of the American Chemical Society,Total Synthesis of (+)-Arborisidine,"The first total synthesis of arborisidine, a unique Kopsia indole alkaloid possessing a fully substituted cyclohexanone ring system with two quaternary carbons, has been achieved in seven steps in racemic format from tryptamine and in nine steps in asymmetric format from d-tryptophan methyl ester. Key elements of the design include a carefully orchestrated decyanation protocol to finalize the asymmetric formation of an aza-quaternary center that is challenging to access in optically active format via direct Pictet-Spengler cyclizations with tryptamine, a metal-promoted 6- endo-dig cyclization of an enyne to establish the second core quaternary center, and regiospecific functionalizations of the resultant complex diene to finalize the target structure. The distinct and efficient nature of the developed solution is highlighted by several unsuccessful approaches and unexpected rearrangements.",10.1021/jacs.9b03248,2019-04-21,0.6249181718642179
Journal of Organic Chemistry,"Cyclic Dipeptides. 3.<sup>1</sup> Synthesis of Methyl (<i>R</i>)-6-[(<i>tert</i>-Butoxycarbonyl)amino]-4,5,6,7- tetrahydro-2-methyl-5-oxo-1,4-thiazepine-3-carboxylate and Its Hexahydro Analogues:  Elaboration of a Novel Dual ACE/NEP Inhibitor","Synthetic routes to highly functionalized 1,4-thiazepinones 2 and 3 have been developed. S-Ac-N-Boc-L-Cys-D(L)-ThrOMe 7a,b have been prepared and, after transformation into the corresponding mesylates, used as the cyclization substrates. Treatment of these compounds with LiAlH(OMe)(3) in THF results in mesylate elimination and thiolacetate reduction, giving rise to both a Michael acceptor (alpha,beta-unsaturated ester) and Michael donor (thiol anion), which undergo in situ intramolecular conjugate addition leading to the stereoselective formation of only two of the four possible stereoisomers of 2. On the other hand, PCC/CaCO(3) oxidation of 7a gave in 80% yield the corresponding ketone 11, which was in turn transformed into the enol triflate 15. Cleavage of the thiolacetate moiety, simultaneous elimination of trifluoromethanesulfonic acid to generate an allene system, and addition of the thiol group to the central carbon of the allene to provide the enantiomerically pure cyclic compound 3 in 85% yield was effected via a one-pot reaction by means of MeONa/MeOH. Thiazepinone 3 is an interesting intermediate for the preparation of conformationally restricted dipeptide mimetics, and its elaboration into the dual ACE/NEP inhibitor 4 is reported.",10.1021/jo981425v,1999-04-01,0.6249060870872677
Journal of Organic Chemistry,3-Aminopyrrolidines from α-Aminoacids:  Total Synthesis of (+)-Nemonapride from <scp>d</scp>-Alanine,The antipsychotic compound nemonapride 1 was synthesized in nine steps from d-alanine 2. The key steps for the synthesis of the 3-aminopyrrolidine moiety include a Birch reduction of a cyclic enaminoester and the reduction of a pyrrolidinone to the pyrrolidine 7. Final coupling with the benzoic acid derivative 9 gave 1 as a single enantio- and diastereomer.,10.1021/jo702278k,2008-01-05,0.6249038741114191
Organic Letters,Gold(I)-Catalyzed Cyclization for the Synthesis of 8-Hydroxy-3- substituted Isocoumarins: Total Synthesis of Exserolide F,"A highly regioselective gold(I)-catalyzed 6-endo-dig cyclization of 2,2-dimethyl-5-(alkynyl)-4H-benzo[d][1,3]dioxin-4-ones for the synthesis of 8-hydroxy-3-substituted isocoumarins is described. Key features of the reaction include the broad substrate scope, scalability, and tolerance for protecting groups. The synthetic utility of this novel method is demonstrated by the first total synthesis of exserolide F, an isocoumarin-containing polyol natural product.",10.1021/acs.orglett.7b00673,2017-04-06,0.6248986058842456
Organic Letters,Total Synthesis of Melonine,"Total synthesis of melonine was accomplished. A cycloheptene unit and a quinoline unit were connected via Stille coupling. The quinoline core was cleaved with thiophosgene to liberate the arylamine moiety. Oxidative intramolecular aziridination, followed by intramolecular nucleophilic attack of the arylamine moiety to the aziridine ring, constructed the characteristic cyclic system with the trans -1,2-diamine structure. Stereoselective hydrogenation and the formation of a piperidine ring led to the synthesis of melonine.",10.1021/acs.orglett.4c04851,2025-02-22,0.6248953020426973
Journal of the American Chemical Society,Palladium-Catalyzed Enantioselective Synthesis of Carbanucleosides,"A general strategy has been developed for enantioselective synthesis of diverse carbanucleosides. The key step is a Pd(0)-catalyzed enantioselective allylic amination of cis -3,5-dibenzoyloxycyclopent-2-ene 10a with the nucleobase. With guanine-derived nucleobase 13 and chiral ligand 9, a 93−96% ee was obtained, while 6-chloropurine and chiral ligand 8 gave 94% ee. The reaction was followed by a second Pd(0)-catalyzed allylic alkylation with phenylsulfonyl(nitro)methane 6 . The nitrosulfone, thus obtained, served as a versatile intermediate for divergent synthesis in which the phenylsulfonyl(nitro)methyl group is a surrogate for the hydroxymethyl side chain. With the guanine-derived nucleobase 13, (−)-carbovir was obtained in only four steps from 10a . With 6-chloropurine as an adenine equivalent, the obtained nitrosulfone intermediate 26 could be converted into both (−)-aristeromycin and (−)-neplanocin A as well as their 2‘,3‘-diepi isomers.",10.1021/ja9938837,2000-06-01,0.6248799714575052
Journal of the American Chemical Society,"A Short and Efficient Synthesis of (−)-7-Methylomuralide, a Potent Proteasome Inhibitor","Short, practical, and scalable syntheses of (+/-)-7-methylomuralide and (-)-7-methylomuralide have been developed. Three consecutive tandem reaction pairs establish all of the carbons and the stereochemistry of the target molecule, vastly simplifying the synthetic scheme from N-trichloroethoxycarbonyl glycine. The chiral directing group controls the absolute stereochemistry of the key aldol reaction.",10.1021/ja901400q,2009-04-01,0.624876722397989
Synlett,A Concise Formal Total Synthesis of (±)-Centrolobine via DDQ-Mediated Diastereoselective Allylation and Ring-Closing Metathesis,"An expedient approach to the construction of arylated 2,6- cis -disubstituted dihydropyran framework was developed involving subsequent DDQ-mediated diastereoselective allylation at an oxygen-substituted benzylic position and ring-closing metathesis (RCM) as key transformations. The synthetic utility of the methodology was illustrated by a formal total synthesis of (±)-centrolobine in five steps from the known homoallylic alcohol or in eight steps from the readily available THP-protected glycidol. This route allows for direct access towards other diarylheptanoid natural products and their synthetic analogues with a variety of side chains.",10.1055/s-0035-1560479,2015-09-18,0.6248749894729672
Tetrahedron,Phosphonium-mediated cyclization of N-(2-aminophenyl)thioureas: efficient synthesis of 2-aminobenzimidazoles,,10.1016/j.tetlet.2011.05.146,2011-06-13,0.6248614452888545
Organic Letters,An Efficient Synthesis of Novel Fused Cycloheptatrienes through Mn(II)-Mediated Formal Intermolecular [2 + 2 + 2 + 1] Cycloaddition,A new method for manganous acetate tetrahydrate mediated formal intermolecular [2 + 2 + 2 + 1] cycloaddition was developed for the synthesis of fused cycloheptatriene derivatives from N-(acylmethyl)pyridinium iodides and naphthoquinone. This method provides an innovative route for the efficient and convenient construction of fused seven-membered carbocycles from simple starting materials.,10.1021/ol500202q,2014-02-24,0.6248593477940291
Synlett,A New Strategy for the Synthesis of Himbacine,"A new strategy for the assembly of himbacine and analogues, which display potent biological activity, is described. A four-step route to a key intermediate has been developed, in which the key step is a highly diastereoselective Michael-Dieckmann domino reaction. Use of an enantioenriched Michael acceptor, readily obtained by an asymmetric dihydroxylation reaction, allowed kinetic resolution of the Michael donor, which was itself prepared by a domino reaction.",10.1055/s-0030-1259918,2011-03-16,0.6248515909692137
Tetrahedron,Total synthesis of (+)-pederin. 2. Stereocontrolled synthesis of (+)-benzoylselenopederic acid and total synthesis of (+)-pederin,,10.1016/s0040-4039(00)99028-2,1985-01-01,0.6248249697933222
Tetrahedron,A convenient synthesis of enantiopure paraconic acid- a key intermediate in the synthesis of A-factor,,10.1016/0040-4039(95)01227-9,1995-08-01,0.6248221837012896
Journal of Organic Chemistry,A Convenient and Scalable Synthesis of Ethyl <i>N</i>-[(2-Boc-amino)ethyl]glycinate and Its Hydrochloride. Key Intermediates for Peptide Nucleic Acid Synthesis,"An improved synthesis of ethyl N-[(2-Boc-amino)ethyl]glycinate and its hydrochloride salt is reported. The synthesis is based on the reductive alkylation of Boc-ethylenediamine with ethyl glyoxylate hydrate and furnishes the title compound in near quantitative yield and high purity without chromatography. This compound is suitable, as is, for the synthesis peptide nucleic acid monomers. Further, conversion to the hydrochloride salt provides a stable, nonhygroscopic solid that is a convenient form for handling and storage.",10.1021/jo026590w,2003-01-22,0.6248196149575255
Synlett,"First Practical Asymmetric Synthesis of a New TetrasubstitutedTetrahydrofuran, (-)-Goniothalesdiol","An efficient and practical strategy has been developed for the construction of the antipode of 3,4-dihydroxy-2,5-disubstituted tetrahydrofuran, goniothalesdiol, isolated from the bark of the Malaysian tree. The synthetic process is based on the convenient manipulation via Lewis acid-induced deoxygenation of the highly functionalized lactone derived from d-glucuronolactone.",10.1055/s-2002-33531,2002-01-01,0.6248145229295418
Angewandte Chemie International Edition,Unified Synthesis of 2‐Isocyanoallopupukeanane and 9‐Isocyanopupukeanane through a “Contra‐biosynthetic” Rearrangement,"Herein, we describe our synthetic efforts toward the pupukeanane natural products, in which we have completed the first enantiospecific route to 2-isocyanoallopupukeanane in 10 steps (formal synthesis), enabled by a key Pd-mediated cyclization cascade. This subsequently facilitated an unprecedented bio-inspired ""contra-biosynthetic"" rearrangement, providing divergent access to 9-isocyanopupukeanane in 15 steps (formal synthesis). Computational studies provide insight into the nature of this rearrangement.",10.1002/anie.202317348,2023-11-30,0.6247948439838438
Journal of Organic Chemistry,"Total Synthesis of Isohericerin, Isohericenone, and Erinacerin A: Development of a Copper-Catalyzed Methylboronation of Terminal Alkynes","Efficient and concise approaches for the synthesis of three bioactive natural products, isohericerin, isohericenone, and erinacerin A, are described in this paper. The key reactions employed include a Mannich reaction with commercially available hydroxybenzoate and subsequent one-pot lactamization to afford the common precursor isoindolinone in 3 steps and a Suzuki-Miyaura coupling reaction to connect geranyl side chains to the isoindolinone core. In addition, the mild and efficient synthesis of the C5'-oxidized geranyl side unit of isohericenone is enabled by developing a highly regioselective and efficient method for the Cu-catalyzed methylboronation of functionalized terminal alkynes.",10.1021/acs.joc.7b00920,2017-05-30,0.6247924258572305
Angewandte Chemie International Edition,Total Synthesis of (+)‐Haplophytine,"A problem solved: Haplophytine (1) yields to total synthesis through a convergent strategy employing modern synthetic methods. Key steps include hypervalent iodine mediated oxidative coupling, semi-pinacol type oxidative skeletal rearrangement, Suzuki–Miyaura coupling, and radical cyclisation.",10.1002/anie.200904588,2009-09-10,0.6247656830749938
Angewandte Chemie International Edition,Enantioselective Total Synthesis of Berkeleyone A and Preaustinoids,"Abstract Herein we report the first enantioselective total synthesis of 3,5‐dimethylorsellinic acid‐derived meroterpenoids (−)‐berkeleyone A and its five congeners ((−)‐preaustinoids A, A1, B, B1, and B2) in 12–15 steps, starting from commercially available 2,4,6‐trihydroxybenzoic acid hydrate. Based upon the recognition of latent symmetry within D‐ring, our convergent synthesis features two critical reactions: 1) a symmetry‐breaking, diastereoselective dearomative alkylation to assemble the entire carbon core, and 2) a Sc(OTf) 3 ‐mediated sequential Krapcho dealkoxycarbonylation/carbonyl α‐ tert ‐alkylation to forge the intricate bicyclo[3.3.1]nonane framework. We also conducted our preliminary biomimetic investigations and uncovered a series of rearrangements (α‐ketol, α‐hydroxyl‐β‐diketone, etc.) responsible for the biomimetic diversification of (−)‐berkeleyone A into its five preaustinoid congeners.",10.1002/anie.202104014,2021-04-16,0.6247655481517156
Tetrahedron,Synthesis and resolution of a new thiahexahelicene,,10.1016/j.tetlet.2012.07.076,2012-07-27,0.62475797432007
Organic Process Research & Development,"Synthesis of 2,4-Di-1-pyrrolidinyl-9H-pyrimido[4,5-b]indoles, Including Antiasthma Clinical Candidate PNU-142731A","Two syntheses are described for 1-[(2,4-di-1-pyrrolidinyl-9H-pyrimido[4,5-b]indol-9-yl)-acetyl]pyrrolidine hydrochloride (PNU-142731A), a clinical candidate in the asthma area. The route involving the initial regioselective addition of glycine ethyl ester to commercially available 2,4,6-trichloropyrimidine is particularly well-suited for large-scale operation, as it is short, proceeds in good yield, is operationally straightforward, and requires no chromatographic purification of intermediates.",10.1021/op000221p,2001-01-16,0.624756319135618
Journal of Organic Chemistry,Stereospecific Approach to the Synthesis of Ring-A Oxygenated <i>Sarpagine</i> Indole Alkaloids. Total Synthesis of the Dimeric Indole Alkaloid <i>P</i>-(+)-Dispegatrine and Six Other Monomeric Indole Alkaloids,"The first regio- and stereocontrolled total synthesis of the bisphenolic, bisquaternary alkaloid (+)-dispegatrine (1) has been accomplished in an overall yield of 8.3% (12 reaction vessels) from 5-methoxy-d-tryptophan ethyl ester (17). A crucial late-stage thallium(III) mediated intermolecular oxidative dehydrodimerization was employed in the formation of the C9-C9' biaryl axis in 1. The complete stereocontrol observed in this key biaryl coupling step is due to the asymmetric induction by the natural sarpagine configuration of the monomer lochnerine (6) and was confirmed by both the Suzuki and the oxidative dehydrodimerization model studies on the tetrahydro β-carboline (35). The axial chirality of the lochnerine dimer (40) and in turn dispegatrine (1) was established by X-ray crystallography and was determined to be P(S). Additionally, the first total synthesis of the monomeric indole alkaloids (+)-spegatrine (2), (+)-10-methoxyvellosimine (5), (+)-lochnerine (6), lochvinerine (7), (+)-sarpagine (8), and (+)-lochneram (11) were also achieved via the common pentacyclic intermediate 16.",10.1021/jo400469t,2013-05-30,0.6247443323926376
Organic Letters,"Total Synthesis of (−)-L-755,807: Establishment of Relative and Absolute Configurations","The first total synthesis of (-)-L-755,807 and its three stereoisomers was achieved by our Horner-Wadsworth-Emmons reaction for stereoselective formation of trisubstituted olefins, highly diastereoselective Darzens condensation to construct the epoxy-γ-lactam ring, and late-stage coupling of the ring and side-chain segments for efficient convergent synthesis. This synthesis shows that the originally proposed structure of natural (-)-L-755,807 was incorrect and establishes its relative and absolute configurations.",10.1021/acs.orglett.6b00758,2016-04-06,0.6247422183897906
Journal of Organic Chemistry,"Synthesis of a Photoactivatable (2<i>S</i>,3<i>R</i>)-Sphingosylphosphorylcholine Analogue","The receptor for the lipid mediator sphingosylphosphorylcholine (SPC) has not yet been identified. We describe here the synthesis of the first photoaffinity analogue of SPC. This probe, which contains a 14C-isotopic label in the choline methyl groups and a photoreactive benzophenone in the long-chain base, may be a useful tool in the identification of the G protein coupled receptors that have been postulated to interact directly and specifically with SPC and in the definition of the ligand-binding sites. The key steps in the synthesis are selective reduction of the triple bond in enyne 6 to install the 4E double bond, Suzuki coupling to incorporate the benzophenone photophore at the end of the sphingoid chain, and reduction of the 2-azidoethyl phosphate headgroup of 13 followed by N,N,N-trimethylation to introduce the radiolabel into the choline moiety. The synthesis was completed by the release of the amino group at C2 of the sphingoid base of SPC analogue 2.",10.1021/jo050513u,2005-05-06,0.6247311285441461
Journal of the American Chemical Society,Total Synthesis of (−)-Mersicarpine,"The total synthesis of (-)-mersicarpine was achieved in 10 steps from a known ketoester. Our synthesis features an Eschenmoser-Tanabe-type fragmentation to synthesize an alkyne unit containing a quaternary carbon center, a facile construction of the indole skeleton via a combination of a Sonogashira coupling and a gold(III) catalyzed cyclization, as well as a one-pot process to arrange the cyclic imine and the hemiaminal moieties. Our synthesis unambiguously confirmed the reported structure of (-)-mersicarpine including the absolute configuration.",10.1021/ja9103233,2010-01-07,0.6247297217680005
Organic Process Research & Development,Scalable Synthesis of Cyclotriphenolene,"Hyperpolarized xenon magnetic resonance imaging ( 129 Xe MRI) is becoming a powerful imaging method that requires cage molecules to encapsulate xenon. Cyclotriphenolene 1 is a key compound for the synthesis of cryptophane cages. A scalable procedure for the synthesis of cyclotriphenolene 1 was developed by which 40 g of 1 can now be synthesized within 3 days, starting from inexpensive benzyl alcohol.",10.1021/op100260w,2011-02-09,0.624729162791345
Tetrahedron,A new reductive acylation of azetidinone disulphide in the route to penems,,10.1016/s0040-4039(00)85519-7,1986-01-01,0.6247203750534901
Journal of the American Chemical Society,Concise Total Synthesis of (−)-Bipolarolide D,"Here we report the first and concise total synthesis of a complex ophiobolin-derived sesterterpene, bipolarolide D, which hinges on two strategic applications of pentafulvene: (1) enantioselective pentafulvene-involved [6+2] cycloaddition; (2) regioselective and diastereoselective pentafulvene-involved Heck cyclization. Late-stage selective allylic addition to the ketone moiety facilitates the successful installation of the side chain. This strategy enabled the accomplishment of its first enantioselective total synthesis through a modular approach. This synthesis will facilitate the investigation of relevant biological activities and provide a synthetic blueprint for utilizing fulvenes as versatile synthons in other complex natural product synthesis.",10.1021/jacs.4c04059,2024-05-08,0.6247160365493449
Synlett,"Short and Efficient Synthesis of (2<i>S</i>)-3-(1′,1′-Dimethylethylsulfonyl) -2-(1-naphthylmethyl)-Propionic Acid,<i>N</i>Terminal Building Block for Protease Inhibitors",All articles of this category Title compound 2 is synthesized (100 g scale) from norephedrine-derived oxazolidinone 3 in three steps in an overall yield of 37% and 99% optical purity.,10.1055/s-1994-22843,1994-01-01,0.6247131228014419
Synlett,First Enantioselective Synthesis of Dendrobatid Alkaloids Indolizidine (-)-209I and (-)-223J,"All articles of this category The first asymmetric synthesis of dendrobatid indolizidine alkaloids (-)-209I [(5 R ,8 R ,8a S )- 1a ] and (-)-223J [(5 R ,8 R ,8a S )- 1b ] via a common late-stage intermediate amino nitrile (5 R ,8 R ,8a S )- 2 are described. Amino nitrile 2 was synthesized employing the highly diastereoselective 1,2-addition of an organocerium reagent to α -substituted aldehyde RAMP-hydrazone ( R , R )- 9 , which was in turn prepared in two steps starting from n -pentanal. The hydrazine obtained in this way was converted to pyrrolidine ( R , S )- 13 , from which amino nitrile (5 R ,8 R ,8a S )- 2 was obtained. Indolizidines (-)-209I and (-)-223J (de = 96 - 99%, ee > 99%) and their C-5 epimers (5 S ,8 R ,8a S )- 1a , b were prepared from 2 by alkylation/stereoselective reduction and stereoselective Bruylants reaction, respectively. asymmetric synthesis - alkaloids - indolizidines - hydrazones - amino nitriles",10.1055/s-2000-8675,2000-01-01,0.6247039168467842
Organic Process Research & Development,"Synthesis of a 5-((Aryloxy)methyl)-3-(4-(trifluoromethyl)phenyl)[1,2,4]thiadiazole Derivative: A Promising PPARα,δ Agonist","The preparation of the PPARα,δ agonist 2-methyl-2-(2-methyl-4-(3-(4-(trifluoromethyl)phenyl)[1,2,4]thiadiazol-5-ylmethoxy)phenoxy)propionic acid sodium salt ( 17 ) is described and compared with earlier in-house preparations of this important target compound. Key concerns around a large-scale synthesis of this thiadiazole derivative were a large number of purification steps, the use of dichlorobenzene as a solvent, and a possible large-scale Baeyer–Villiger oxidation. This paper describes a straightforward preparation of the target agonist using methylhydroquinone (MHQ) as an inexpensive precursor that eliminates the need of an oxidation step.",10.1021/op700141u,2007-11-01,0.6246999029422188
Organic Letters,Asymmetric Total Synthesis of (+)-Chuanxiongnolide L1 via a Stereoselective Oxidative Dearomatization/Diels–Alder Strategy,The first asymmetric total synthesis of chuanxiongnolide L1 was achieved in 16 steps and 1.9% overall yield by employing a bioinspired chiral auxiliary strategy. The key steps involving asymmetric oxidative dearomatization of chiral amino ether and subsequent asymmetric Diels–Alder reaction of the resulting masked chiral ortho -benzoquinone were adopted.,10.1021/acs.orglett.4c00411,2024-03-29,0.6246876487710155
Organic Letters,Asymmetric Synthesis of (−)-Martinellic Acid,"A high-yielding total asymmetric synthesis of (-)-martinellic acid is reported. The conjugate addition of lithium (R)-N-allyl-N-(α-methyl-4-methoxybenzyl)amide to tert-butyl (E)-3-[2'-(N,N-diallylamino)-5'-bromophenyl]propenoate and alkylation of the resultant β-amino ester have been used as the key steps to install the C(9b) and C(3a) stereogenic centers, respectively, and a highly diastereoselective Wittig reaction/intramolecular Michael addition was then used to create the C(4) stereogenic center within this tricyclic molecular architecture.",10.1021/ol4007508,2013-04-04,0.6246874225736897
Angewandte Chemie International Edition,Inside Cover: Catalytic Selective Cyclizations of Aminocyclopropanes: Formal Synthesis of Aspidospermidine and Total Synthesis of Goniomitine (Angew. Chem. Int. Ed. 33/2010),"Selective cyclization of aminocyclopropanes on either the N1 or C3 positions of the indole ring is described by J. Waser and co-workers in their Communication on page 5767 ff. This methodology was used in the synthesis of the Apocynaceae alkaloids. A copper(I) catalyst gave access to the core of aspidospermidine, and a Brønsted acid was used in the total synthesis of goniomitine, which demonstrated significant cytotoxicity against tumor cell lines (IC50=150–400 nM).",10.1002/anie.201003240,2010-06-22,0.6246870800276989
Journal of Organic Chemistry,"Convergency and Divergency as Strategic Elements in Total Synthesis:  The Total Synthesis of (−)-Drupacine and the Formal Total Synthesis of (±)-Cephalotaxine, (−)-Cephalotaxine, and (+)-Cephalotaxine","A concise route toward the syntheses of (-)-drupacine and (+)- and (-)-cephalotaxine has been developed. The syntheses rely on Pd(II)-catalyzed aerobic oxidative heterocyclization chemistry, which was employed to rapidly construct an important spirocyclic amine intermediate. A dynamic beta-elimination/conjugate addition process was strategically applied to complete the first asymmetric total synthesis of (-)-drupacine.",10.1021/jo0710883,2007-08-18,0.6246830635012659
Journal of Organic Chemistry,Synthesis of Novel Carbocyclic Adenosine Analogues as Inhibitors of Adenosine Kinase,"Several new 4‘-amino substituted carbocyclic adenosine analogues ( 6, 7, 31 ) were prepared as potential inhibitors of the enzyme adenosine kinase. Three different heterocyclic base moieties (adenine, 8-azaadenine, and pyrazolo[3,4- d ]pyrimidine) were incorporated into carbocyclic nucleoside analogues through the use of two different synthetic strategies. In both strategies, bicyclic isoxazolidine 9 (prepared through a hetero Diels−Alder reaction with cyclopentadiene) was used as the starting material. In one route, the N−O bond was reductively cleaved, and the hydroxyl group (after inversion and ring functionalization) was used as a leaving group to incorporate the heterocyclic base moiety as the key bond-forming step. A second, more efficient and higher yielding synthetic route was developed as a general solution to the synthesis of the target 4‘-amino substituted carbocyclic adenosine analogues. In this methodology, the allylic C−O bond in the bicyclic isoxazolidine 9 was cleaved with double stereoinversion under palladium(0) catalysis as the key bond-forming step to stereospecifically incorporate the heterocyclic base moiety into the cyclopentane ring. The regioselectivity of key bond-forming steps was established principally by NMR methods, especially through 13 C NMR shifts and by NOE effects seen in the analogues, as well as by HMBC/HMQC experiments.",10.1021/jo981658m,1999-03-18,0.6246808838690259
Journal of Organic Chemistry,Porphyrin synthesis through tripyrrins: an alternate approach,"A new route for synthesis of unsymmetrically substituted porphyrins is described. The route follows the earlier approach through pyrromethanes, tripyrrin hydrobromides, and a,c-biladiene dihydrobromides, except that the pyrromethane intermediate is elongated in an initially “clockwise” direction to give a benzyl tripyrrincarboxylate. Various advantages over the tert-butyl tripyrrincarboxylates used in the earlier method (Scheme I) are discussed. The new route is demonstrated in the syntheses of five pure porphyrins required for other current studies. © 1983, American Chemical Society. All rights reserved.",10.1021/jo00171a029,1983-11-01,0.6246782491527672
Tetrahedron,Practical synthesis of (R)-γ-amino-β-hydroxybutanoic acid (GABOB) from (R)-epichlorohydrin,,10.1016/s0040-4039(00)95420-0,1987-01-01,0.6246673662280192
Tetrahedron,Synthesis of (S)-3-hydroxytetrahydropyran from l -glutamic acid,,10.1016/j.tetlet.2017.09.008,2017-09-07,0.6246605231712148
Tetrahedron,"Synthesis of dehydro-1,3-dimethyluric acid",,10.1016/s0040-4039(00)98040-7,1990-01-01,0.6246605231712148
Tetrahedron,Synthesis of tethered phytic acid,,10.1016/s0040-4039(00)85982-1,1991-04-01,0.6246605231712148
Tetrahedron,Synthesis of (−)-Warburganal and 4α-methoxycarbonyl congener from 1-abietic acid,,10.1016/s0040-4039(00)87028-8,1982-01-01,0.6246605231712148
Tetrahedron,Synthesis of cadeguomycin (7-deazaguanosine-7-car☐ylic acid),,10.1016/s0040-4039(00)88191-5,1983-01-01,0.6246605231712148
Tetrahedron,A biomimetic synthesis of stizolobinic acid,,10.1016/s0040-4039(97)00467-x,1997-04-01,0.6246605231712148
Tetrahedron,Synthesis of γ-acylmethylenetetronates from squaric acid,,10.1016/s0040-4039(00)74094-9,1993-07-01,0.6246605231712148
Tetrahedron,Synthesis of 5′-deoxyuridine 5′-phosphonic acid,,10.1016/s0040-4039(00)90598-7,1967-01-01,0.6246605231712148
Tetrahedron,An enantiospecific synthesis of polyoxamic acid from L-arabinose,,10.1016/s0040-4039(01)80736-x,1989-01-01,0.6246605231712148
Tetrahedron,"Synthesis of monomethyl 5,5′-dehydrodiferulic acid",,10.1016/j.tetlet.2015.01.002,2015-01-08,0.6246605231712148
Tetrahedron,Synthesis of (-)-ambrox from ℓ-abietic acid,,10.1016/s0040-4039(00)96229-4,1987-01-01,0.6246605231712148
Tetrahedron,Synthesis of juniperonic acid,,10.1016/j.tetlet.2010.03.085,2010-03-26,0.6246605231712148
Tetrahedron,"Synthesis of grevillins and their biogenetic interrelationship with terphenylquinones, xylerythrins and pulvinic acid",,10.1016/s0040-4039(00)96616-4,1987-01-01,0.6246605231712148
Tetrahedron,Stipitatic acid: synthesis via cyclopropanated quinones,,10.1016/s0040-4039(00)98258-3,1985-01-01,0.6246605231712148
Tetrahedron,Synthesis of ()-β-fluoromethyleneglutamic acid,,10.1016/s0040-4039(00)89300-4,1985-01-01,0.6246605231712148
Tetrahedron,Synthesis of (±)-homogabaculine and (±)-homoshikimic acid,,10.1016/s0040-4039(00)92128-2,1991-02-01,0.6246605231712148
Tetrahedron,Synthesis of an oxa-lipoic acid,,10.1016/j.tetlet.2007.04.132,2007-05-02,0.6246605231712148
Tetrahedron,Synthesis of podoscyphic acid,,10.1016/s0040-4039(01)02264-x,2002-01-01,0.6246605231712148
Tetrahedron,Stereocontrolled synthesis of (+)-thienamycin from 3(R)-hydroxybutyric acid,,10.1016/s0040-4039(00)98542-3,1985-01-01,0.6246605231712148
Tetrahedron,"Synthesis of thymidinephosphorothioyl -(O3′→ O5′)-thymidine via phosphorothioic acid O,O,S-triester",,10.1016/s0040-4039(01)95679-5,1973-01-01,0.6246605231712148
Tetrahedron,First synthesis of lycoperdic acid,,10.1016/s0040-4039(00)74730-7,1992-12-01,0.6246605231712148
Tetrahedron,Synthesis of carba-sugars from (−)-quinic acid,,10.1016/s0040-4039(01)00601-3,2001-06-01,0.6246605231712148
Tetrahedron,Synthesis of robustic acid,,10.1016/s0040-4039(01)84431-2,1972-02-01,0.6246605231712148
Tetrahedron,Synthesis of thomasidioic acid,,10.1016/s0040-4039(01)95701-6,1973-01-01,0.6246605231712148
Tetrahedron,A synthesis of bufalin from deoxycholic acid,,10.1016/s0040-4039(00)84555-4,1986-01-01,0.6246605231712148
Tetrahedron,"The synthesis of 6,6-difluoroshikimic acid",,10.1016/j.tetlet.2004.03.033,2004-03-29,0.6246605231712148
Tetrahedron,Synthesis of ibotenic acid,,10.1016/s0040-4039(00)90158-8,1965-01-01,0.6246605231712148
Tetrahedron,Synthesis of the C-1 sidechain of the squalestatins and zaragozic acid A,,10.1016/0040-4039(94)88298-3,1994-10-01,0.6246605231712148
Tetrahedron,The synthesis of 4-epidehydroabietic acid,,10.1016/s0040-4039(00)89492-7,1968-01-01,0.6246605231712148
Tetrahedron,Synthesis of (±)-coronafacic acid,,10.1016/s0040-4039(01)83500-0,1977-01-01,0.6246605231712148
Tetrahedron,"Synthesis of (-)-Muricatacin and (-)-(5R,6S)-6-acetoxy-5-hexadecanolide, the Mosquito oviposition attractant pheromone, from D-isoascorbic acid",,10.1016/0040-4039(94)88177-4,1994-01-01,0.6246605231712148
Tetrahedron,Synthesis of a radioactive photoaffinity arachidonic acid analog,,10.1016/s0040-4039(00)76742-6,1994-03-01,0.6246605231712148
Tetrahedron,Synthesis of micrococcinic acid,,10.1016/s0040-4039(00)92144-0,1991-01-01,0.6246605231712148
Tetrahedron,The first synthesis of vancomycinic acid,,10.1016/s0040-4039(00)73316-8,1994-07-01,0.6246605231712148
Tetrahedron,The synthesis of γ-fluoroglutamic acid,,10.1016/s0040-4039(01)99323-2,1960-01-01,0.6246605231712148
Tetrahedron,The synthesis of 3- and 4-deuterated shikimic acid,,10.1016/s0040-4039(00)85910-9,1983-01-01,0.6246605231712148
Tetrahedron,Stereocontrolled synthesis of gibberellin A19 from gibberellic acid,,10.1016/s0040-4039(01)80818-2,1985-01-01,0.6246605231712148
Tetrahedron,Synthesis of 5-O-carbamoyl-polyoxamic acid,,10.1016/s0040-4039(01)87646-2,1973-01-01,0.6246605231712148
Tetrahedron,The komppa synthesis of camphoric acid,,10.1016/s0040-4039(01)98968-3,1968-01-01,0.6246605231712148
Tetrahedron,Synthesis of (+)-taxodione from (−)-abietic acid,,10.1016/s0040-4039(00)82181-4,1988-01-01,0.6246605231712148
Tetrahedron,"Assymetric synthesis of (2S,3R)- and (2S,3S)-[2-13C;3-2H] glutamic acid",,10.1016/j.tetlet.2009.01.062,2009-01-20,0.6246605231712148
Tetrahedron,Synthesis of (±)-nephromopsinic acid,,10.1016/s0040-4039(98)01550-0,1998-09-01,0.6246605231712148
Tetrahedron,A flexible synthesis of some polysubstituted cyclopentanes from quinic acid,,10.1016/s0040-4039(00)76724-4,1994-06-01,0.6246605231712148
Tetrahedron,A synthesis of puraquinonic acid,,10.1016/s0040-4039(01)00144-7,2001-03-01,0.6246605231712148
Tetrahedron,Synthesis of neoaspergillic acid,,10.1016/s0040-4039(01)89044-4,1965-01-01,0.6246605231712148
Tetrahedron,The synthesis of flavensomycinic acid,,10.1016/s0040-4039(01)99908-3,1966-01-01,0.6246605231712148
Tetrahedron,Synthesis of diastereoisomeric ent-isocopalic acid glycerides,,10.1016/0040-4039(96)00609-0,1996-05-01,0.6246605231712148
Tetrahedron,Synthesis of berninamycinic acid,,10.1016/s0040-4039(01)81179-5,1984-01-01,0.6246605231712148
Tetrahedron,Synthesis of saramycetic acid,,10.1016/j.tetlet.2007.07.111,2007-07-31,0.6246605231712148
Tetrahedron,Synthesis of 2-benzamido-2-mercaptopropanoic acid,,10.1016/s0040-4039(01)97095-9,1971-01-01,0.6246605231712148
Tetrahedron,Synthesis of the xantholaccaic acid B system,,10.1016/s0040-4039(01)81882-7,1981-01-01,0.6246605231712148
Tetrahedron,Synthesis of gibberellin a12 from -abietic acid,,10.1016/s0040-4039(00)71298-6,1976-04-01,0.6246605231712148
Tetrahedron,From phenylaziridine to phenylkainoids. A formal synthesis of (±)-phenylkainic acid,,10.1016/s0040-4039(99)00611-5,1999-05-01,0.6246605231712148
Tetrahedron,Chirospecific synthesis of (+)-PS-5 from L-glutamic acid,,10.1016/s0040-4039(00)80482-7,1988-01-01,0.6246605231712148
Tetrahedron,Synthesis of prostanoic acid,,10.1016/s0040-4039(00)91098-0,1975-01-01,0.6246605231712148
Organic Letters,Enantiospecific Synthesis of the Antituberculosis Marine Sponge Metabolite (+)-Puupehenone. The Arenol Oxidative Activation Route,"[formula: see text] The total synthesis of the marine sesquiterpene quinone (+)-puupehenone, a promising new antituberculosis agent, was achieved in 10 steps starting from commercially available (+)-sclareolide. The key feature of this synthesis is the construction of the heterocycle via an intramolecular attack of the terpenoid-derived C-8 oxygen function onto an oxidatively activated 1,2-dihydroxyphenyl unit.",10.1021/ol026855t,2002-10-01,0.6246604418679422
Journal of the American Chemical Society,Enantioselective Total Synthesis of Cotylenin A,"A convergent enantioselective total synthesis of cotylenin A is described. The A-ring fragment, prepared via the catalytic asymmetric intramolecular cyclopropanation developed in our laboratory, and the C-ring fragment, prepared from a known chiral compound via a modified acyl radical cyclization, were successfully assembled by the Utimoto coupling reaction. The formidable carbocyclic eight-membered ring of cotylenin A was efficiently constructed by a palladium-mediated cyclization. All the hydroxy groups in the scaffold were stereoselectively introduced, and a modified reducing reagent, Me 4 NBH(O 2 C i Pr) 3, has been developed. The sugar moiety fragment was prepared via three consecutive carbon–oxygen bond-forming reactions, and the glycosylation was accomplished using Wan’s protocol.",10.1021/jacs.0c01774,2020-03-13,0.62465583383288
Journal of Organic Chemistry,A Novel Synthesis of (+)-Biotin from <scp>l</scp>-Cysteine,"(+)-Biotin (1) was synthesized in 25% overall yield over 11 steps from L-cysteine. The contiguous asymmetric centers at C-3a and C-6a were formed through a novel and highly stereoselective Lewis base-catalyzed cyanosilylation of alpha-amino aldehyde 3 to provide anti-O-TMS-cyanohydrin 4 with high stereoselectivity and in high yield (anti/syn = 92:8, 96%). Treatment of 4 with a di-Grignard reagent, 1,4-bis(bromomagnesio)butane, followed by carbon dioxide, efficiently installed the 4-carboxybutyl chain at C-4 to give keto acid 5. The final cyclization to bicyclic compound 7b, a precursor to 1, was realized by a palladium-catalyzed intramolecular allylic amination of cis-allylic carbonate 6b that was elaborated from 5.",10.1021/jo025794+,2002-07-04,0.6246482533732503
Organic Process Research & Development,Synthetic Development and Scale-Up of a Complex Pyrazole Fragment of Lenacapavir,"We describe herein the process development and scale-up of a complex cyclopropyl pyrazole fragment of lenacapavir, a drug recently approved for long-acting treatment of HIV (Sunlenca). A ten-step asymmetric synthesis was developed utilizing simple starting materials capable of supporting the commercial supply chain of lenacapavir. Key aspects of this development effort were the oxidation strategy to elaborate the core and optimization of the fluorination reaction to afford the final product.",10.1021/acs.oprd.4c00235,2024-07-31,0.6246469352143925
Tetrahedron,Synthetic studies on asperparaline A.Synthesis of the spirosuccinimide ring system,,10.1016/s0040-4039(99)00825-4,1999-06-01,0.624646363302091
Tetrahedron,Synthetic studies towards gambierol. Part 1: Synthesis of the AB ring segment,,10.1016/s0040-4039(01)01204-7,2001-08-01,0.624646363302091
Tetrahedron,Synthetic studies towards gambierol. Part 2: Synthesis of the EFGH ring segment,,10.1016/s0040-4039(01)01205-9,2001-08-01,0.624646363302091
Tetrahedron,"Synthetic studies on paraherquamide: synthesis of the 2H-1,5. Benzodioxepin ring system",,10.1016/s0040-4039(00)97054-0,1990-01-01,0.624646363302091
Journal of Organic Chemistry,"Synthesis of a New Stable Conformationally Constrained 2,7-Anhydrosialic Acid Derivative","A stereoseletive synthesis of 2,7-anhydrosialic acid derivative 18 was achieved from d-glucono-delta-lactone. A highly syn-selective addition of Grignard reagent to theN-benzylimine 8 served as a key step.",10.1021/jo034679b,2003-11-01,0.6246378474068253
Journal of Organic Chemistry,"Rearrangements of Cyclobutenones. Synthesis of <i>N</i>-Methyl-7,8-dihydrobenzophenanthridine-9,12-diols and Related Compounds",A useful synthetic route to benzophenanthridines and annulated derivatives is reported. These arise from the thermolysis (refluxing chlorobenzene) of squaric acid-derived 4-(3- N -methyl- N -arylpropynyl)-cyclobutenones via a mechanism which involves an electrocyclic ring opening of the cyclobutenone to the corresponding enynylketenes. Subsequent ring closure to a diradical intermediate followed by radical arylation gives the benzophenanthridines.,10.1021/jo990505b,1999-07-20,0.6246353785361977
Journal of Organic Chemistry,"Direct, Two-Step Synthetic Pathway to Novel Dibenzo[<i>a,c</i>]phenanthridines","Novel dibenzo[a,c]phenanthridines are prepared regioselectively by the application of a straightforward synthetic pathway, starting from new 3,4-diaryl- and 3,4-dihydro-3,4-diarylisoquinolines prepared via Ritter-type heterocyclization and the more classical two-step reductive amination/Bischler-Napieralski cyclization of triarylethanones, respectively. A comparative study of nonphenolic oxidative coupling methodologies provides a highly efficient procedure, based on the hypervalent iodine reagent phenyliodine(III) bis(trifluoroacetate) (PIFA), to accomplish the final coupling step.",10.1021/jo0501036,2005-03-23,0.6246320950713548
Journal of Organic Chemistry,Total Synthesis of the Cyclopeptide Alkaloid Abyssenine A. Application of Inter- and Intramolecular Copper-Mediated Coupling Reactions in Organic Synthesis,The first total synthesis of the 15-membered ring cyclopeptide alkaloid abyssenine A 1 has been achieved with a longest linear sequence of 15 steps. Central to the synthetic approach was an efficient copper-mediated Ullmann coupling/Claisen rearrangement sequence allowing for both ipso and ortho functionalization of aromatic iodide 4. This sequence was used for the synthesis of the aromatic core. The synthetic utility of copper-catalyzed coupling reactions was further demonstrated to install the enamide with a concomitant straightforward macrocyclization starting from acyclic alpha-amido-omega-vinyl iodide 13.,10.1021/jo070517u,2007-05-18,0.6246234708201143
Organic Process Research & Development,"Process Development for a Locally Acting SGLT1 Inhibitor, LX2761, Utilizing sp<sup>3</sup>–sp<sup>2</sup> Suzuki Coupling of a Benzyl Carbonate","Process development for the synthesis of a locally acting sodium-dependent glucose cotransporter 1 (SGLT1) inhibitor, LX2761, a drug candidate for the treatment of diabetes mellitus, is described. A convergent route based on a retrosynthetic disconnection of the central diarylmethane linkage to a benzyl carbonate and a hindered arylboronic ester was designed and developed. The syntheses of these fully elaborated, late-stage crystalline intermediates are discussed, along with optimization of their union via an sp 3 –sp 2 Suzuki–Miyaura coupling reaction. The final active pharmaceutical ingredient was isolated in high purity as its l -proline cocrystal. This process was successfully performed on a kilogram scale to support toxicology and preclinical studies.",10.1021/acs.oprd.8b00325,2018-12-24,0.6246094104952464
Synlett,"A Concise Synthesis of Fused Tricyclic Pyrrolo[3,2-d]pyrimidines","A concise approach to partially saturated fused tricyclic pyrrolo[3,2- d ]pyrimidines has been developed. Herein, we report a three-step route to the core templates, starting with a Sonogashira coupling and utilising either a CuI-catalysed or base-mediated 5- endo - dig cyclisation to form the pyrrolopyrimidine ring, followed by Mitsunobu cyclisation to afford the tricyclic system. This method facilitates synthetic access to a structural class with limited representation in the literature and is amenable to further elaboration by virtue of a halide incorporated at the 4-position.",10.1055/s-0035-1561482,2016-07-06,0.6246082709641978
Organic Process Research & Development,"Development of a Scalable Synthesis of GSK183390A, a PPAR α/γ Agonist","A scalable synthesis of GSK183390A, a PPAR α/γ agonist, is described. This synthesis is highlighted by (1) a regioselective formal 1,3-dipolar cycloaddition reaction between an enamine and a nitrile imine dipole to form a 1,3,5-trisubstituted pyrazole and (2) a regioselective amidomethylation of an ο -cresol derivative using 2-chloro- N -hydroxymethylacetamide.",10.1021/op700164t,2007-11-01,0.6245957519807945
Organic Letters,"Total Syntheses of 7,20-Oxa-Bridged Dinorditerpenes: Antihepatitis C Virus Active (+)-Elevenol from <i>Flueggea virosa</i> and (+)-Przewalskin","An efficient stereoselective synthetic approach to 7-20 oxa-bridged abietane type natural products is reported. Key steps are an asymmetric Mukaiyama aldol addition to construct the C3 stereocenter and an intramolecular organocatalyzed Stetter-type Michael addition followed by a Tishchenko reaction. An intramolecular lactone-enolate arylation delivers the tetracyclic skeleton. This synthetic strategy was applied for the first total synthesis of (+)-elevenol, an antihepatitis C active compound from Fluegga virosa, and the first total synthesis of (+)-przewalskin.",10.1021/acs.orglett.6b02922,2016-10-18,0.6245895923468365
Angewandte Chemie International Edition,Total Synthesis of Gracilioether F: Development and Application of Lewis Acid Promoted Ketene–Alkene [2+2] Cycloadditions and Late‐Stage CH Oxidation,"The first synthesis of gracilioether F, a polyketide natural product with an unusual tricyclic core and five contiguous stereocenters, is described. Key steps of the synthesis include a Lewis acid promoted ketene-alkene [2+2] cycloaddition and a late-stage carboxylic acid directed C(sp(3) )H oxidation. The synthesis requires only eight steps from norbornadiene.",10.1002/anie.201408055,2014-10-30,0.624585593192622
Synlett,A Concise Route to the Key Intermediate of (+)-Vernolepin Using A Bicyclo[3.2.1]octane Chiral Building Block,"An enantioselective route to the key intermediate leading to (+)-vernolepin, an antitumor sesquiterpene, isolated from Vernonia hymenolepis, has been developed starting from the chiral building block having a bicyclo[3.2.1]octane framework accessible by either enzymatic or catalytic kinetic resolution.",10.1055/s-2002-32603,2002-01-01,0.6245830344077044
Organic Process Research & Development,Development of a Scalable Process for the Crop Protection Agent Isoclast,A scalable process to the insecticide Isoclast manufactured by Dow AgroSciences LLC is described. The process involves the de novo construction of a fully elaborated pyridine sulfide using enamine-mediated cyclization followed by two efficient and inexpensive oxidations to introduce the sulfoximine.,10.1021/acs.oprd.5b00007,2015-02-20,0.6245714454379996
Synthesis,"Stereoselective Total Syntheses of Solifenacin and N-Acetyl-1-(4-chlorophenyl)-6,7-dimethoxytetrahydroisoquinoline","A highly stereoselective synthesis of 1-aryl-1,2,3,4-tetrahydroisoquinoline drugs such as solefinacin (muscarinic acetylcholine receptor antagonist) and N -acetyl-1-(4-chlorophenyl)-6,7-dimethoxytetrahydroisoquinoline (AMPA receptor antagonist) has been accomplished using ( R )- tert -butanesulfinamide as a chiral source. Chiral tetrahydroisoquinolines have been prepared through the aryl Grignard addition to chiral N -sulfinylimines followed by haloamide cyclization.",10.1055/s-0034-1378515,2014-07-16,0.6245632126431263
Journal of Organic Chemistry,Improved Plasmalogen Synthesis Using Organobarium Intermediates,"An improved synthesis of plasmalogen type lipids is described. Transmetalation of lithioalkoxy allyl intermediates with BaI(2) and subsequent alkylation with 1-iodoalkanes enables the stereoselective formation of O-(Z)-alkenyl ether as precursors for the synthesis of plasmenyl- and bisplasmenylcholines. This method provides a simple and adaptable approach for the stereocontrolled synthesis of plasmenyl derivatives with variations at the sn-1, sn-2, and sn-3 positions of the glycerol backbone.",10.1021/jo0705059,2007-06-01,0.6245625641519067
Synthesis,"Synthesis of a Benzo[5,6]cyclohepta[1,2-b]thiophene and Thieno[3,2-c]benzazepine Derivatives","A new series of 2-methyl-4-(4-methylpiperazin-1-yl)-10H-benzo[5,6]cyclohepta[1,2-b]thiophene (5) and 2-methyl-4-(4-methylpiperazin-1-yl)thieno[3,2-c][1]benzazepine derivatives 6b-f have been synthesized from 2-methylthiophene and phthalic anhydride. Preparation of the key intermediate 2-methyl-4,5-dihydro-10H-benzo[5,6]cyclohepta[1,2-b]thiophene-4-one (12) and 2-methylthieno[3,2-c][1]benzazepine-4(5H),10-dione (16) were carried out by intramolecular dehydration of the phenylacetic acid 11 and Lewis acid associated cyclization of the isocyanate 14, respectively.",10.1055/s-2002-20033,2002-01-01,0.6245615680259321
Organic Process Research & Development,Development of an Efficient Synthesis of (2-Aminopyrimidin-5-yl) Boronic Acid,A practical and cost-effective synthesis of (2-aminopyrimidin-5-yl) boronic acid 1b has been developed. Key features of the synthesis include the inexpensive in situ protection of the amine via bis-silylation using TMSCl followed by metal–halogen exchange using n -BuLi and trapping with B(O i -Pr) 3 . The water-soluble boronic acid is isolated by a well-designed acid–base sequence providing the target in 80% yield and high purity for the two-step process. The large-scale (15 kg) implementation of a Suzuki–Miyaura borylation to form the pinacol boronic ester is also described.,10.1021/acs.oprd.5b00360,2015-12-22,0.6245443951736829
Synthesis,An Efficient and Safe Method for the Multigram Synthesis of trans-2-(Trifluoromethyl)cyclopropylamine,"trans-2-(Trifluoromethyl)cyclopropylamine was prepared on a multigram scale from readily accessible 4,4,4-trifluorobut-2-enoic acid in five steps. The key step was a high-yielding cyclopropane ring formation from 4,4,4-trifluorobut-2-enoic acid methoxymethyl amide under Corey-Chaykovsky reaction conditions.",10.1055/s-0031-1289711,2012-02-15,0.6245259675973917
Organic Letters,Synthesis of Fasicularin,"The synthesis of a tricyclic marine alkaloid, fasicularin, was accomplished. Stereoselective synthesis of the aza-spirocyclic BC-ring precursor and ensuing construction of the A-ring with stereocontrolled installation of the C2 hexyl group feature prominently in the synthesis.",10.1021/acs.orglett.6b01669,2016-06-29,0.6245195067718257
Journal of the American Chemical Society,Evolution of a Strategy for the Enantioselective Synthesis of (−)-Cajanusine,The first enantioselective synthesis of (-)-cajanusine is presented. Key features of the route include a rapid synthesis of the [4.2.0]bicyclooctane core by an enantioselective isomerization/stereoselective [2+2]-cycloaddition strategy as well as prominent use of catalytic methods for bond construction. The evolution of the approach is also presented that highlights unexpected roadblocks and how novel solutions were developed.,10.1021/jacs.0c00359,2020-03-09,0.6245014492314602
Tetrahedron,"A convergent synthesis approach towards CGP60536B, a non-peptide orally potent renin inhibitor, via an enantiomerically pure ketolactone intermediate",,10.1016/s0040-4039(00)01794-9,2000-12-01,0.624492254158298
Organic Letters,Bioinspired Synthesis of Pygmaeocins and Related Rearranged Abietane Diterpenes: Synthesis of Viridoquinone,"A bioinspired synthesis of rearranged abietane diterpenes, related to pygmaeocins, is described. In this process, the key step is the 1,2-migration of the C-20 angular methyl to the C-5 position of the abietane skeleton, which occurs when a C6–C7 unsaturated dehydroabietane derivative is treated with SeO 2 in dioxane under reflux (19 examples for this rearrangement are described). Utilizing this reaction, an enantiospecific synthesis of pygmaeocin C and the first synthesis of viridoquinone, starting from the abietane phenol ferruginol, are reported. A tentative mechanism for this reaction and a possible biosynthetic pathway for this family of metabolites are postulated.",10.1021/acs.orglett.8b02395,2018-09-13,0.6244871329983874
Organic Letters,Enantioselective Total Syntheses of Pentacyclic Homoproaporphine Alkaloids,"Herein we report the first enantioselective total syntheses of pentacyclic homoproaporphine alkaloids by means of a route, which includes a tandem retro-oxa-Michael addition and nucleophilic substitution to generate the oxa-benzobicyclco[3.3.1]nonane core structure, a Pictet-Spengler cyclization to construct the fused B and C rings, and sequential Baeyer-Villiger oxidation and pinacol-type cyclization to install the hydroxyl-lactol moiety of D ring. With this unified route, six pentacyclic homoproaporphine alkaloids have been synthesized enantioselectively.",10.1021/acs.orglett.0c02720,2020-09-16,0.6244858179710191
Journal of the American Chemical Society,Total Synthesis of Gelsemoxonine through a Spirocyclopropane Isoxazolidine Ring Contraction,"Plants of the species Gelsemium have found application in traditional Asian medicine for over a thousand years. Gelsemoxonine represents a novel constituent of this plant incorporating a highly functionalized azetidine at its core. We herein report a full account of our studies directed toward the total synthesis of gelsemoxonine that relies on a conceptually new approach for the construction of the central azacyclobutane. A spirocyclopropane isoxazolidine ring contraction was employed to access a key β-lactam intermediate, which could be further elaborated to the azetidine of the natural product. In the course of our studies, we have gained detailed insight into this intriguing transformation. Furthermore, we report on previously unnoticed oligomerization chemistry of gelsemoxonine. We also document an enantioselective synthesis of a key precursor en route to gelsemoxonine.",10.1021/jacs.5b02574,2015-04-13,0.6244719995857102
Tetrahedron,Copper nanoparticles on charcoal: an effective nanocatalyst for the synthesis of enol carbamates and amides via an oxidative coupling route,,10.1016/j.tetlet.2015.11.072,2015-11-25,0.62446914470446
Tetrahedron,The synthesis of new acridinium salt aquatic antifungals,,10.1016/s0040-4039(00)79276-8,1993-11-01,0.6244669355284636
Journal of Organic Chemistry,Total Synthesis of (−)-Dihydrosporothriolide Utilizing an Indium-Mediated Reformatsky–Claisen Rearrangement,"The asymmetric synthesis of (-)-dihydrosporothriolide (1), a biologically active bis-γ-butyrolactone, is described, that proceeds through a D-proline-catalyzed asymmetric aminooxylation, indium-mediated Reformatsky-Claisen rearrangement of an α,α-dibromoacetate derivative, and diastereoselective dihydroxylation. The route requires no protective group manipulation and allows the concise seven-step synthesis of 1 from n-octanal.",10.1021/jo5008948,2014-05-30,0.624465866533632
Journal of Organic Chemistry,Total Synthesis and Evaluation of C26-Hydroxyepothilone D Derivatives for Photoaffinity Labeling of β-Tubulin,"Three photoaffinity labeled derivatives of epothilone D were prepared by total synthesis, using efficient novel asymmetric synthesis methods for the preparation of two important synthetic building blocks. The key step for the asymmetric synthesis of (S,E)-3-(tert-butyldimethylsilyloxy)-4-methyl-5-(2-methylthiazol-4-yl)pent-4-enal involved a ketone reduction with (R)-Me-CBS-oxazaborolidine. For the synthesis of (5S)-5,7-di[(tert-butyldimethylsilyl)oxy]-4,4-dimethylheptan-3-one an asymmetric Noyori reduction of a beta-ketoester was employed. The C26 hydroxyepothilone D derivative was constructed following a well-established total synthesis strategy and the photoaffinity labels were attached to the C26 hydroxyl group. The photoaffinity analogues were tested in a tubulin assembly assay and for cytotoxicity against MCF-7 and HCT-116 cancer cell lines. The 3- and 4-azidobenzoic acid analogues were found to be as active as epothilone B in a tubulin assembly assay, but demonstrated significantly reduced cellular cytotoxicity compared to epothilone B. The benzophenone analogue was inactive in both assays. Docking and scoring studies were conducted that suggested that the azide analogues can bind to the epothilone binding site, but that the benzophenone analogue undergoes a sterically driven ligand rearrangement that interrupts all hydrogen bonding and therefore protein binding. Photoaffinity labeling studies with the 3-azidobenzoic acid derivative did not identify any covalently labeled peptide fragments, suggesting that the phenylazido side chain was predominantly solvent-exposed in the bound conformation.",10.1021/jo901752v,2009-12-02,0.6244638069458555
Journal of Organic Chemistry,Synthetic Studies on Ezomycins: Stereoselective Route to a Thymine Octosyl Nucleoside Derivative,"The ezomycins are Streptomyces-derived antifungal natural products, belonging to the complex peptidyl nucleoside family of antibiotics. Employing D-serine as a chiral platform, we report herein a novel synthetic route to the bicyclic octosyl nucleoside core of the ezomycins. A key step in the sequence involved a stereoselective 6-exo-trig oxymercurationoxidation of a strategic delta-hydroxy alkene derivative, toward construction of the trans-fused furopyran ring system as present in the target products. In contrast to the known carbohydrate-based synthetic routes to the above furopyranyl fragment, the present amino acid chiral template approach is expected to offer a more flexible pathway toward potential SAR-targeted structural/stereochemical modifications of this central bicyclic nucleoside component of the ezomycins.",10.1021/jo801050r,2008-07-04,0.6244506581499929
Journal of Organic Chemistry,A Photochemical Route to 3- and 4-Hydroxy Derivatives of 2-Aminocyclobutane-1-carboxylic Acid with an <i>all-cis</i> Geometry,"Short gram-scale syntheses of both enantiomers of 2-amino-3-hydroxycyclobutane-1-carboxylic acid and of 2-amino-4-hydroxycyclobutanecarboxylic acid with an all-cis geometry are described. The sequences feature highly endo-selective [2 + 2]-photocycloaddition reactions followed by fully regioselective ring opening/Hofmann rearrangement/nitrogen protection, in a consecutive or one-pot protocol, followed by efficient resolution using a chiral oxazolidinone.",10.1021/acs.joc.7b02559,2017-12-01,0.6244375661355123
Tetrahedron,Enantioselective preparation of key [ABC] intermediates for steroid synthesis through the asymmetric Michael addition process involving chiral imines.,,10.1016/s0040-4039(00)80513-4,1988-01-01,0.6244298350599878
Organic Letters,A Concise Approach for the Total Synthesis of Pseudolaric Acid A,"A new strategy for the stereoselective total synthesis of natural product pseudolaric acid A (1) was accomplished in 16 steps from commercially available starting material, featuring a samarium diiodide (SmI(2))-mediated intramolecular alkene-ketyl radical cyclization and a ring-closing metathesis (RCM) reaction to stereoselectively cast the unusual trans-fused [5-7]-bicyclic core of pseudolaric acid A (1).",10.1021/ol200741j,2011-04-27,0.6244272461115807
Synlett,A Short and Efficient Synthesis of Licochalcone E,Licochalcone E was synthesized concisely via an abnormal Claisen rearrangement and Claisen-Schmidt condensation as the key reactions in a three-step sequence. The overall yield is 20% starting from prenyl bromide and 4-hydroxy-2-methoxybenzaldehyde.,10.1055/s-0030-1258029,2010-08-12,0.624416252882232
Synthesis,First Total Synthesis of the Marine Natural Product Viscosamine,"Pyridinium alkaloids are widely distributed in marine sponges of the order Haplosclerida. The cyclic trimeric 3-alkylpyridinium alkaloid viscosamine, from the Arctic sponge Haliclona viscosa, was synthesised through a ten-step synthesis starting from pyridylalcohol in 8% overall yield. Key steps involved the simultaneous activation and deprotection of an open chain precursor, followed by cyclisation under highly dilution conditions. Viscosamine is the first cyclotrimeric 3-alkylpyridinium natural product obtained by total synthesis.",10.1055/s-2006-942477,2006-07-25,0.6244104098238358
Organic Process Research & Development,Development of the Carbocyclic Nucleoside MDL 201449A:  A Tumor Necrosis Factor-α Inhibitor,"An efficient synthesis of (1 S,4 R )-(−)-4- tert -butyldimethylsilyloxy-2-cyclopentenyl acetate and (1 R,4 S )-(−)-4- tert -butyldimethylsilyloxy-2-cyclopentenol is described utilizing a furfuryl alcohol rearrangement, followed by a lithium aluminum hydride reduction with high facial selectivity and an efficient enzymatic resolution with pancreatin. Both of these intermediates were successfully utilized in the preparation of the carbocyclic nucleoside 9 N -[(1‘ R,3‘ R )- trans -3‘-hydroxycyclopentanyl]adenine hydrochloride, an agent which inhibits the formation of tumor necrosis factor-α.",10.1021/op9701245,1998-09-12,0.6244067202673661
Tetrahedron,Synthesis of 2H-pyrroles by treatment of pyrrolidines with DDQ,,10.1016/s0040-4039(03)00740-8,2003-04-01,0.6244056147692802
Organic Process Research & Development,"Synthesis of ((3<i>R</i>,6<i>R</i>)-6-Methylpiperidin-3-yl)methanol via Biocatalytic Transamination and Crystallization-Induced Dynamic Resolution","An asymmetric synthesis of orexin receptor antagonist MK-6096 piperidine core, ((3 R,6 R )-6-methylpiperidin-3-yl)methanol ( 3 ), is described. The target is synthesized in four steps and 40% overall yield from methyl vinyl ketone and diethyl malonate. The key operation is a practical crystallization-induced dynamic resolution for the conversion of a trans/cis mixture of lactam acid 17 into the desired trans-lactam acid salt in >95% de and 91% yield. The substrate lactam acid mixture was prepared via a solvent-free Michael reaction and a practical biocatalytic transamination process.",10.1021/acs.oprd.5b00259,2015-09-22,0.6244028969687515
Angewandte Chemie International Edition,"Enantioselective Synthesis of the Core of Banyaside, Suomilide, and Spumigin HKVV",Concise: The first synthesis of the unique azabicyclononane core found in the aeruginosin class of serine protease inhibitors is described. The route is characterized by its efficiency (eight steps) and sets the stage for subsequent introduction of the glycosyl and peptidyl side chains that differentiate the members of the aeruginosin family of natural products.,10.1002/anie.200803655,2008-10-15,0.624401359609013
Organic Process Research & Development,Some Items of Interest to Process R&amp;D Chemists and Engineers,"Improved Pd-Catalyzed Aryl Chloride Cyanations Using Sulfate AdditivesThe Pd-catalyzed cyanation of aryl chlorides can still be challenging due to the more difficult oxidative insertion step into C-Cl bonds and competing catalyst deactivation caused by soluble cyanide.A recent report from Shevlin at Merck describes the use of sulfate additives to improve the robustness of Pd-catalyzed cyanations (Tetrahedron Lett.2010, 51, 4833-4836).Additives such as H 2 SO 4 greatly increase the reactivity of palladium catalysts for the cyanation of aryl and heteroaryl chlorides and render these reactions more robust toward adventitious air.Using this method, a wide variety of aromatic and heteroaromatic nitriles were prepared in high yield.Experiments to completely understand the role of the sulfate additives are ongoing. Synthesis of Antituberculosis Candidate PA-824Tuberculosis (TB) is a devastating bacterial infection that kills more than 1.8 million people each year worldwide.Compound PA-824 is being developed by the Global Alliance for TB Drug Development (GATB) and is now in advanced phase II clinical trials.The original synthesis used to obtain material for clinical trials provides PA-824 in five linear steps from 2,4-dinitroimidazole, an intermediate with risk of explosion.Furthermore, the synthesis requires four chromatographic separations and an inefficient protection-deprotection sequence in order to selectively construct the oxazine core.Now Reider, Sorensen, and Marsini at Princeton report a new efficient fourstep synthesis of PA-824 (J.Org.Chem.2010, 75, 7479-7482).This new route employs (R)-3-chloro-1,2-propanediol, which is readily available from epichlorohydrin via HKR.Selective protection with a p-methoxybenzoyl group yields an intermediate that can be benzylated on the secondary alcohol and then reacted with 2-chloro-4-nitroimidazole under basic conditions to displace the chloride.Last, treatment with a stronger base (KOH in MeOH) results in cleavage of the benzoate ester and cyclization to form the oxazine ring.This concise approach offers significant improvements over the synthetic route currently used for large-scale production.",10.1021/op100321t,2010-12-23,0.6243977554212721
Tetrahedron,A new synthetic route for construction of the core of zaragozic acids,,10.1016/s0040-4039(99)00256-7,1999-04-01,0.6243864625884453
Tetrahedron,Palladium-catalyzed one-pot Suzuki–Miyaura cross coupling followed by oxidative lactonization: a novel and efficient route for the one-pot synthesis of benzo[c]chromene-6-ones,,10.1016/j.tetlet.2012.11.144,2012-12-07,0.6243803114809227
Organic Letters,Synthesis of the AB Subunit of Angelmicin B through a Tandem Alkoxy Radical Fragmentation-Etherification Sequence,"The synthesis of the tricyclic enone 2, corresponding to the AB subunit of the novel tyrosine kinase inhibitor angelmicin B, is described. The strategy centers on an intramolecular Diels-Alder (IMDA) reaction on triene 4 to provide the complex decalin 3, which is elaborated to 2. Other key steps are the formation of the THF ring in 2 through a tandem alkoxy radical fragmentation-etherification on the lactol derived from 3, and the synthesis of 4 via a ring-closing ene-yne metathesis (RCEYM).",10.1021/ol703036y,2008-03-07,0.6243788785047765
Organic Process Research & Development,Multikilogram-Scale Synthesis of a Chiral Cyclopropanol and an Investigation of the Safe Use of Lithium Acetylide–Ethylene Diamine Complex,"A six-step route starting from a readily available vinyl boronate was identified to produce an enantioenriched cyclopropanol in an overall 16% yield. Key steps involve the use of lithium acetylide-ethylene diamine complex 5 and an enzymatic resolution of a racemic cyclopropanol acetate. Process safety considerations surrounding the use of 5 were examined, and an improved procedure is described which was safely demonstrated at multikilogram scale.",10.1021/op2002497,2011-12-07,0.6243770031147029
Organic Letters,Synthesis of the C(2)−C(13) Fragment (The A−B Spiroketal Unit) of Spongistatin 1 (Altohyrtin A):  Use of a Common Intermediate for the Synthesis of Both Spongistatin Spiroketals,"[reaction: see text] A convergent synthesis of 14 corresponding to the A-B spiroketal core of spongistatin 1 has been accomplished via an iodo-spiroketalization reaction of glycal 9, which was synthesized in three steps from a late-stage intermediate used in our synthesis of the C-D spiroketal fragment of spongistatin 1. Elaboration of 14 to the A-B spiroketal 15 was accomplished in three steps.",10.1021/ol026688x,2002-09-17,0.6243693129901349
Organic Process Research & Development,New Robust Synthetic Strategy toward the Radiopharmaceutical Labeling Precursor FAPI-46,"The radiolabeled FAPI-46 has been extensively employed as a diagnostic and therapeutic agent for malignancies. Based on our endeavor to reproduce the synthetic route of FAPI-46, we systematically elucidate the practical challenges encountered. Then, our effort in optimizing the synthetic route of FAPI-46 characterized by practicality, cost-effectiveness, and high reproducibility was presented here. Initially, we have explored four routes for synthesizing the key intermediate 19, among which the one that obtained 24 via the Pd 2 (dba) 3 -catalyzed C–N coupling between methyl quinoline-4-carboxylate 20 and silyl-protected 3-hydroxypropylamine 23, followed by desilylation and sulfonylation of the hydroxyl group of 24, proved to be the optimal route to obtain 19 . Subsequently, the condensation of lithium quinoline-4-carboxylate 34 with nitrile-pyrrole-substituted amine 8 using N,N,N′N ′ -tetramethylchloroformamidinium hexafluorophosphate (TCFH) as the condensing agent to afford 9 demonstrated a notably streamlined process and satisfactory yield. This feasible and robust strategy offered a valuable procedure for the large-scale production of FAPI-46 and its analogues containing the quinoline-4-carboxylic acid scaffold.",10.1021/acs.oprd.5c00267,2025-11-18,0.6243679966813126
Journal of Organic Chemistry,"Efficient Synthesis of Novel 1α-Amino and 3β-Amino Analogues of 1α,25-Dihydroxyvitamin D<sub>3</sub>","Convenient synthetic routes to 1alpha-amino-25-hydroxyvitamin D(3) (3) and 3beta-amino-3-deoxy-1alpha,25-dihydroxyvitamin D(3) (4), novel analogues of vitamin D(3) bearing an amino group at the C-1 or C-3 position, have been developed starting from (S)-(+)-carvone. Construction of the A-ring fragments was accomplished by selective enzymatic hydrolysis of a diester intermediate and introduction of the amino group under Mitsunobu conditions.",10.1021/jo026474t,2002-12-20,0.6243679016290777
Synthesis,Synthesis of Angular Pyrrolocoumarins,"The new pyrrolocoumarin 3 was synthesized in two steps from 7-amino-4-methylcoumarin by selective o-chloroacetylation at position 8 and subsequent cyclization (the Sugasawa route to indoles). Regioselective inverse electron demand Diels-Alder reaction of 3 with dimethyl 1,2,4,5-tetrazine-3,6-dicarboxylate or 3,6-bis(trifluoromethyl)-1,2,4,5-tetrazine then gave the angular pyridazinepyrrolocoumarins 4 and 5, respectively, in good yield.",10.1055/s-2002-20952,2002-01-01,0.6243576710866381
Organic Process Research & Development,Manufacturing Synthesis of 5-Substituted Phthalides,"A manufacturing synthesis of 5-chlorophthalide has been elaborated. The key step of the procedure is ortho-lithiation of 4-chloro -N,N -diisopropylbenzamide, followed by formylation with dimethyl formamide. Reduction of the formyl moiety and subsequent ring closure, which can be carried out also in one pot, led to 5-chlorophthalide in high overall yield. The procedure has also been successfully adapted for the synthesis of the 5-fluoro and 5-trifluoromethyl analogues. The compounds thus obtained are useful building blocks in the synthesis of various heterocyclic ring systems.",10.1021/op100049t,2010-04-15,0.6243401467977191
Synlett,Synthetic Studies Towards Crinine-Type Amaryllidaceae Alkaloids: Synthesis of (±)-Oxocrinine and Formal Synthesis of (±)-Crinine,"A flexible strategy leading to the synthesis of crinine-type Amaryllidaceae alkaloids, (±)-oxocrinine and (±)-crinine, has been developed. A notable feature in this synthetic route is the construction of tetrahydro-1H-benzo[c]azepine framework using an intramolecular Heck reaction and the formation of the sterically congested spiro cyclohexenone intermediate with a Robinson annulation.",10.1055/s-0030-1259288,2010-12-23,0.6243380343031447
Tetrahedron,"A stereocontrolled route to the synthesis of (±)-3-amino-2,2-dimethyl-1,3-diphenylpropan-1-ol",,10.1016/j.tetlet.2010.09.011,2010-09-16,0.6243143504496537
Organic Letters,"Enantioselective Synthesis of 2-Deoxy- and 2,3-Dideoxyhexoses","[reaction: see text] The enantioselective syntheses of C-6 O-TBS- and N-Cbz-protected 2-deoxy- and 2,3-dideoxysugars have been achieved in 6-8 steps from furfural. A combination of chemo-, regio-, and diastereoselective oxidation and reduction reactions produced deoxysugars with various C-6 substitution. A key development of this route was the use of o-nitrobenzenesulfonylhydrazide (NBSH) as a diimide precursor. These overall procedures allow for the synthesis of eight deoxysugars in either enantiomeric form.",10.1021/ol025844x,2002-04-23,0.6243120468675237
Journal of Organic Chemistry,Asymmetric Total Synthesis of (+)-Luciduline: Toward a General Approach to Related <i>Lycopodium</i> Alkaloids,"As part of a research program directed toward the synthesis of Lycopodium alkaloids, a multigram scale asymmetric synthesis of intermediate 11 was achieved in 11 steps from pyridine (17). In addition to our alkene metathesis strategy, a key feature of this synthetic approach consists of a Fukuyama's Diels-Alder cycloaddition between 1,2-dihydropyridine and acrolein using MacMillan's catalyst (18) on a 50 g scale. This led to a 12-step catalytic asymmetric synthesis of (+)-luciduline (1). A broader subset of Lycopodium alkaloids could also be obtained, as demonstrated by the derivatization of 11 into advanced intermediates for the synthesis of some of these natural products.",10.1021/jo200745n,2011-05-20,0.6243103487357016
Journal of the American Chemical Society,Total Synthesis of the Strychnos Alkaloid (+)-Minfiensine: Tandem Enantioselective Intramolecular Heck−Iminium Ion Cyclization,"A 1,2,3,4-tetrahydro-9a,4a-(iminoethano)-9H-carbazole (4) is a central structural feature of the Strychnos alkaloid minfiensine (1) and akuammiline alkaloids such as vincorine (5) and echitamine (6). A cascade catalytic asymmetric Heck-iminium cyclization was developed that rapidly provides 3,4-dihydro-9a,4a-(iminoethano)-9H-carbazoles in high enantiomeric purity. Two sequences were developed for advancing 3,4-dihydro-9a,4a-(iminoethano)-9H-carbazole 27 to (+)-minfiensine. In our first-generation approach, a reductive Heck cyclization was employed to form the fifth ring of (+)-minfiensine. In a second more concise total synthesis, an intramolecular palladium-catalyzed ketone enolate vinyl iodide coupling was employed to construct the final ring of (+)-minfiensine. This second-generation total synthesis of enantiopure (+)-minfiensine was accomplished in 6.5% overall yield and 15 steps from 1,2-cyclohexanedione and anisidine 13. A distinctive feature of this sequence is the use of palladium-catalyzed reactions to form all carbon-carbon bonds in the transformation of these simple precursors to (+)-minfiensine.",10.1021/ja800163v,2008-02-28,0.6243007086966303
Synthesis,A Simple Synthesis of 2′-Deoxy-3′-Thioinosine and Its Phosphorothioamidite,"5′- O -{[Bis(4-methoxyphenyl)(phenyl)methyl])-2′-deoxy-3′-thioinosine and its S -phosphorothioamidite were prepared in five and six steps, respectively, from commercially available 2′-deoxyinosine. The key 3′-thio intermediate was synthesized by two sequential configuration inversions: a one-pot oxidation/reduction reaction and an S N 2 reaction. This intermediate was readily converted into the target compound with a high yield. Compared with other methods, this synthetic strategy has the advantages of brief reaction steps, a relatively high overall yield, and regioselectivity for the configuration inversions. The products might be useful as intermediates for the preparation of new functionalized nucleosides.",10.1055/s-0032-1317713,2012-12-11,0.6242896940095152
Journal of the American Chemical Society,"Convergent Total Synthesis of Principinol D, a Rearranged Kaurane Diterpenoid","The total synthesis of principinol D, a rearranged kaurane diterpenoid, is reported. This grayanane natural product is constructed via a convergent fragment coupling approach, wherein the central seven-membered ring is synthesized at a late stage. The bicyclo[3.2.1]octane fragment is accessed by a Ni-catalyzed α-vinylation reaction. Strategic reductions include a diastereoselective SmI 2 -mediated ketone reduction with PhSH and a new protocol for selective ester reduction in the presence of ketones. The convergent strategy reported herein may be an entry point to the larger class of kaurane diterpenoids.",10.1021/jacs.9b03751,2019-05-02,0.6242841616469547
Organic Letters,Formal Synthesis of 7-Methoxymitosene and Synthesis of its Analog via a Key PtCl<sub>2</sub>-Catalyzed Cycloisomerization,"A formal synthesis of 7-methoxymitosene is achieved via a key platinum-catalyzed cycloisomerization. The precursor for the Pt catalysis, a fully functionalized benzene intermediate, was prepared via a regioselective electrophilic bromination followed by a chemoselective Sonogashira cross-coupling. It underwent the PtCl2-catalyzed cycloisomerization smoothly despite its hindered and highly electron-rich nature. Analogs of 7-methoxymitosene can be accessed in an expedient manner by following a similar synthetic sequence.",10.1021/ol301593w,2012-07-05,0.6242796224832322
Journal of Organic Chemistry,"Development of a Flexible and Robust Synthesis of Tetrahydrofuro[3,4-<i>b</i>]furan Nucleoside Analogues","In the context of a PRMT5 inhibitor program, we describe our efforts to develop a flexible and robust strategy to access tetrahydrofuro[3,4- b ]furan nucleoside analogues. Ultimately, it was found that a Wolfe type carboetherification from an alkenol derived from d -glucofuranose diacetonide was capable of furnishing the B-ring and installing the desired heteroaryl group in a single step. Using this approach, key intermediate 1.3-A was delivered on a gram scale in a 62% yield and 9.1:1 dr in favor of the desired S -isomer. After deprotection of 1.3-A, a late-stage glycosylation was performed under Mitsunobu conditions to install the pyrrolopyrimidine base. This provided serviceable yields of nucleoside analogues in the range of 31–48% yield. Compound 1.1-C was profiled in biochemical and cellular assays and was demonstrated to be a potent and cellularly active PRMT5 inhibitor, with a PRMT5-MEP50 biochemical IC 50 of 0.8 nM, a MCF-7 target engagement EC 50 of 3 nM, and a Z138 cell proliferation EC 50 of 15 nM. This work sets the stage for the development of new inhibitors of PRMT5 and novel nucleoside chemical matter for alternate drug discovery programs.",10.1021/acs.joc.0c02969,2021-03-23,0.6242738040679218
Organic Letters,Synthesis of Tylocrebrine and Related Phenanthroindolizidines by VOF<sub>3</sub>-Mediated Oxidative Aryl-Alkene Coupling,"A highly convergent strategy to prepare phenanthroindolizidines is reported involving three consecutive C-C coupling reactions. This sequence features a novel VOF(3)-mediated aryl-alkene coupling in the final step, which enables regioselective preparation of C5-substituted phenanthroindolizidines for the first time. This strategy has been applied to the synthesis of eight natural and unnatural members in this class to investigate the scope of this chemistry and to explore structure-activity relationships.",10.1021/ol1023954,2010-12-14,0.6242694661849852
Organic Letters,"Synthesis of γ-Lactones via the Kowalski Homologation Reaction: Protecting-Group-Free Divergent Total Syntheses of Eupomatilones-2,5,6, and 3-<i>epi</i>-Eupomatilone-6","A highly efficient synthesis of functionalized chiral γ-butyrolactone scaffolds has been described. The basis of the approach is the Kowalski ester homologation that is modified for our proposed transformation. The newly developed methodology combines a divergent synthetic strategy to permit a straightforward protecting-group-free asymmetric total syntheses of eupomatilones-2,5,6, and 3- epi -eupomatilone-6 in five or six steps from commercial starting materials, making it one of the shortest syntheses reported to date.",10.1021/acs.orglett.9b02848,2019-09-26,0.6242588399880391
Tetrahedron,Synthesis of novel protected hemiaminal N-methoxymeothyl-N′-methyl-99′-biacridylidene from lucigenin,,10.1016/s0040-4039(00)91798-2,1993-02-01,0.624241404337399
Journal of Organic Chemistry,Total Synthesis of Nominal <i>ent</i>-Chlorabietol B,"The nominal enantiomer of chlorabietol B was regio- and stereoselectively synthesized from (−)-abietic acid in 13 steps. Key features of the synthesis involved an oxidative [3+2] cycloaddition to install the dihydrobenzofuran moiety and an Aldol reaction, followed by elimination and reduction steps to introduce the long chain with three cis double bonds. However, obvious differences in the NMR spectra of the synthetic and natural samples suggested that the proposed structure of chlorabietol B should be revised carefully.",10.1021/acs.joc.0c00233,2020-03-26,0.6242272214136212
Organic Process Research & Development,Preparation of (<i>S</i>)-1-Cyclopropyl-2-methoxyethanamine by a Chemoenzymatic Route Using Leucine Dehydrogenase,"( S )-1-Cyclopropyl-2-methoxyethanamine is a key chiral intermediate for the synthesis of a corticotropin-releasing factor-1(CRF-1) receptor antagonist. Resolution of the racemic amine by transaminase from Vibrio fluvalis gave a 38% yield of the S -amine with 53% ee. Resolution by lipase-catalyzed acylation provided the S -amine in 35% yield with 91% ee. With limited success of these resolution approaches, an efficient chemo-enzymatic route to ( S )-1-cyclopropyl-2-methoxyethanamine was devised starting from methylcyclopropyl ketone. Permanganate oxidation of the ketone gave cyclopropylglyoxylic acid, which was converted to ( S )-cyclopropylglycine by reductive amination using leucine dehydrogenase from Thermoactinomyces intermedius with NADH cofactor recycling by formate dehydrogenase from Pichia pastoris . Both enzymes were cloned and expressed in recombinant E. coli . ( S )-Cyclopropylglycine obtained from enzymatic reductive amination was isolated as the N -Boc derivative and converted to the desired amine by reduction, methylation, and deprotection to give ( S )-1-cyclopropyl-2-methoxyethanamine in 62% overall yield from cyclopropylglyoxylic acid, with no detectable R -enantiomer.",10.1021/op2003562,2012-02-17,0.6242184866554024
Journal of Organic Chemistry,"Total Syntheses of Angelicoin A, Hericenone J, and Hericenol A via Migratory Prenyl- and Geranylation–Aromatization Sequences",A five-step synthesis of the natural product angelicoin A using a late stage highly regioselective palladium(0)-catalyzed decarboxylative prenyl migration and aromatization sequence as the key step is reported. The method was extended with geranyl migration in eight-step total syntheses of hericenone J and hericenol A from geraniol.,10.1021/jo202354j,2011-11-22,0.6242177277530017
European Journal of Organic Chemistry,Novel Approach to the (–)‐Sparteine‐Mediated Synthesis of Kainoids:Total Synthesis of (–)‐α‐Kainic Acid by (–)‐Sparteine‐Mediated Deprotonation,"Abstract We report a new synthesis of kainoids via allyllithium compounds using an intramolecular cycloalkylation as the key step. Preparation of different substituted pyrrolidines was carried out by using carbamates, that react with the chiral base n ‐BuLi/(–)‐sparteine with strong selection between the diastereotopic protons adjacent to the carbamate group in favour for the pro‐S proton. (–)‐α‐Kainic acid was synthetized from D ‐serine methyl ester hydrochloride, based on a (–)‐sparteine‐mediated asymmetric deprotonation of an intermediate carbamate that, by stereospecific anti ‐S N ′S E ′ intramolecular cycloalkylation, leads to the pyrrolidine ring precursor of (–)‐α‐kainic acid, in high yield and diastereoselectivity. Related approaches, starting from L ‐glutamic acid failed. The intermediate pyrrolidine was further transformed to (–)‐α‐kainic in three steps. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2005)",10.1002/ejoc.200400824,2005-04-01,0.624215588747824
Tetrahedron,Asymmetric synthesis of 3-benzofuranones through 5-exo-trig cyclization of 4-nitroaryl olefins,,10.1016/j.tetlet.2016.06.118,2016-06-28,0.6242123349284048
Tetrahedron,"Asymmetric 1,4-additions to γ-menthyloxybutenolides. Enantiospecific synthesis of chiral 1,4-butanediols",,10.1016/s0040-4039(01)80599-2,1989-01-01,0.6242107895945941
Tetrahedron,Asymmetric synthesis with chiral hydroxylamines.,,10.1016/s0040-4039(00)95680-6,1987-01-01,0.6242107895945941
Tetrahedron,"First asymmetric synthesis of chiral 1,4-benzodioxane lignans",,10.1016/s0040-4039(00)00820-0,2000-08-01,0.6242107895945941
Tetrahedron,Chiral cyclopropanes: asymmetric synthesis of constanolactones A and B,,10.1016/s0040-4039(02)00699-8,2002-05-01,0.6242107895945941
Tetrahedron,Methylpyroglutamate as chiral synthon : asymmetric synthesis of antihypertensive pyrrolidines,,10.1016/0040-4039(88)85136-0,1988-01-01,0.6242107895945941
Organic Letters,Bioinspired Collective Total Synthesis of (±)-Rhynchines A–E,"Herein, we present the first racemic total synthesis of the structurally complex monoterpene indole alkaloids rhynchines A–E, starting from commercially available methyl nicotinate and 3-(2-bromoethyl)-1 H -indole. The success of our synthesis is attributed to the utilization of a bioinspired synthetic strategy, which facilitated the rapid construction of the pentacyclic core skeleton of the target molecules through biomimetic skeletal rearrangement and late-stage C–H oxidative cyclization. Additionally, silica-gel-promoted tautomerization played a crucial role as a strategic element in the chemical synthesis of rhynchines A and B.",10.1021/acs.orglett.4c00727,2024-04-02,0.6242086610218203
Tetrahedron,A new efficient synthetic process for the construction of the pentacyclic core of marine alkaloid ecteinascidins,,10.1016/s0040-4039(03)01785-4,2003-09-01,0.624202616974701
Tetrahedron,Synthetic studies on prostanoids 1 synthesis of methyl 9-oxoprostanoate,,10.1016/s0040-4039(01)84569-x,1972-01-01,0.624202472930035
Angewandte Chemie International Edition,Practical Route to Neokotalanol and Its Natural Analogues: Sulfonium Sugars with Antidiabetic Activities,"An efficient and divergent approach toward the synthesis of all four de-O-sulfonated sulfonium type α-glucosidase inhibitors, originally isolated from plants of genus Salacia, is reported for the first time. The key strategy features a coupling reaction between thiol derivatives and a diiodide counterpart. The newly designed thiol coupling partner presents high chemical stability, while the diiodide partner could be easily obtained with increased overall yields compared with conventional routes. The intermolecular nucleophilic substitution reaction followed by a diastereoselective intramolecular cyclization provided the target five-member sulfonium salt structure, which was connected in an α-orientation to a polyhydroxylated side-chain moiety.",10.1002/anie.201900761,2019-02-28,0.6241863902317991
European Journal of Organic Chemistry,"Application of Selective Palladium‐Mediated Functionalization of the Pyrido[3′,2′:4,5]pyrrolo[1,2‐<i>c</i>]pyrimidine Heterocyclic System for the Total Synthesis of Variolin B and Deoxyvariolin B","Abstract The reaction of protected 3‐bromo‐2‐(bromomethyl)‐4‐methoxypyrrolo[2,3‐ b ]pyridine and tosylmethyl isocyanide (TosMIC) afforded a pyrido[3′,2′:4,5]pyrrolo[1,2‐ c ]pyrimidine derivative in good yield. This compound was transformed through installation of the pyrimidine moiety in the C5 position, hydrolysis, and decarboxylation in an advanced intermediate for the total or formal synthesis of the naturalalkaloid variolin B. Reaction of 3‐bromo‐2‐(bromomethyl)‐4‐chloropyrrolo[2,3‐ b ]pyridine with N ‐tosylmethyl dichloroformimide as a synthetic TosMIC equivalent afforded trihalo‐substituted pyrido[3′,2′:4,5]pyrrolo[1,2‐ c ]pyrimidine. This compound was used in a new total synthesis of the alkaloid variolin B by selective and sequential C–N, C–C, and C–O palladium‐mediated functionalization at the C9, C5, and C4 positions of the pyrido[3′,2′:4,5]pyrrolo[1,2‐ c ]pyrimidine system. A formal synthesis of deoxyvariolin B is also described by using the same synthetic strategy.",10.1002/ejoc.201000599,2010-08-24,0.6241834808483376
European Journal of Organic Chemistry,Total Synthesis of 3‐Oxo‐ and 3β‐Hydroxytauranin via Negishi Coupling of a Bis(<i>ortho</i>‐oxy)‐Functionalized Benzyl Chloride,"Abstract The first asymmetric synthesis of the sesquiterpene quinones 3‐oxo‐ and 3β‐hydroxytauranin ( 1 , 2 ) was achieved and the originally proposed structure of 3α‐hydroxytauranin was revised. The protected benzyl chloride 5 was obtained in six steps starting from 4‐bromo‐3,5‐dihydroxybenzoic acid ( 8 ) via a highly scalable approach. The troublesome Negishi coupling of the benzyl chloride 5 with alkenyldimethylalane 6 was optimized to furnish all ‐ trans ‐farnesylarene 14 in very good yield. This prenylated arene was transformed in six additional steps to 3β‐hydroxytauranin ( 2 ). Finally, a new convenient access to propargylated terpenes without using dry cryogenic ammonia and gaseous allene or propyne is described.",10.1002/ejoc.201500815,2015-08-14,0.6241729702744812
Tetrahedron,A new hydroxylation route: introduction of the trimethylsilyloxy group,,10.1016/s0040-4039(01)87687-5,1969-01-01,0.6241727296679465
Tetrahedron,An improved synthesis of the potent and selective γ-glutamyl transpeptidase inhibitor GGsTop together with an inhibitory activity evaluation of its potential hydrolysis products,,10.1016/j.tetlet.2017.08.019,2017-08-08,0.6241695515197156
Angewandte Chemie International Edition,Convergent Synthesis of Deoxypropionates,"Metallacycle-mediated allylic alcohol–alkyne reductive cross-coupling is described as a convergent solution to the synthesis of deoxypropionates. This approach offers superior step-economy in comparison to available strategies based on multistep iterative chain elongation. The technique is demonstrated in a concise synthesis of the C1–C11 subunit of borrelidin, and a total synthesis of (−)-vittatalactone.",10.1002/anie.201200035,2012-04-05,0.6241657139519611
Journal of Organic Chemistry,Stereoselective Total Synthesis of (−)-Renieramycin T,"A stereoselective total synthesis of (-)-Renieramycin T (1t) from a key tetrahydroisoquinoline intermediate previously utilized in our formal total synthesis of Ecteinascidin 743 is described. The synthesis features a concise approach for construction of the pentacyclic framework using a Pictet-Spengler cyclization of bromo-substituted carbinolamine 17, which obviates the regioselectivity problem of the Pictet-Spengler cyclization. The results of cytotoxicity studies are also presented.",10.1021/acs.joc.6b00327,2016-03-28,0.6241596146391925
Tetrahedron,Synthesis of the A ring segment of gambieric acid,,10.1016/s0040-4039(01)00529-9,2001-05-01,0.6241434761619408
Tetrahedron,Synthesis of the J ring segment of gambieric acid,,10.1016/s0040-4039(01)00530-5,2001-05-01,0.6241434761619408
Tetrahedron,Synthesis of novel dendrimers incorporating a dye into the core,,10.1016/s0040-4039(01)00533-0,2001-05-01,0.6241394646543906
Journal of Organic Chemistry,Efficient Synthesis of 2‘<i>-C-</i>β-Methylguanosine,"2'-beta-Methyl nucleosides have potential value as therapeutic agents and as nucleoside analogues for exploring RNA biology. Here we develop a strategy for efficient synthesis for 2'-C-beta-methylguanosine (3). Starting from 1,2,3,5-tetra-O-benzoyl-2-C-beta-methyl-d-ribofuranose (1) and N2-acetylguanine, we obtained the title compound in two steps (78% overall yield) with high stereoselectivity (beta/alpha > 99:1) and high regioselectivity (N9/N7 > 99:1). Extension of this strategy to the classic synthesis of guanosine also resulted in high stereoselectivity (beta/alpha = 99:1) and improved regioselectivity (N9/N7 = 97:3).",10.1021/jo0602165,2006-04-20,0.6241207679292036
Tetrahedron,Chiral diamines for asymmetric synthesis: an efficient RCM construction of the ligand core of (−)- and (+)-sparteine,,10.1016/j.tetlet.2005.08.106,2005-09-16,0.6241128267603867
Organic Letters,Synthesis of the Prelog–Djerassi Lactone via an Asymmetric Hydroformylation/Crotylation Tandem Sequence,"A synthesis of the Prelog-Djerassi lactone [(+)-1] has been accomplished in three isolations and 57% overall yield from the known vinyl ortho ester 2. A Rh(I)-catalyzed asymmetric hydroformylation/crotylation tandem sequence has been developed and used to set the C2-C4 stereochemistry. A Rh(I)-catalyzed asymmetric hydrogenation was employed to set the C6 sterechemistry, resulting in an unusually short and efficient enantioselective synthesis of this touchstone molecule from achiral starting material.",10.1021/ol3008765,2012-05-04,0.6240946369225827
Reaction Chemistry & Engineering,"Efficient and convenient synthesis of methyl ( <i>S</i> )-5-chloro-2-hydroxy-1-oxo-2,3-dihydro-1 <i>H</i> -indene-2-carboxylate: a key intermediate for ( <i>S</i> )-indoxacarb using aqueous TBHP as oxidant","The work reports an improved method for the efficient, stereoselective and industrially feasible synthesis of the key intermediate for ( S )-indoxacarb, which features purification by filtration, using aqueous TBHP as an oxidant and mild conditions.",10.1039/d4re00510d,2025-01-01,0.6240768722693169
Organic Letters,Stereoselective Synthesis of the C9–C19 Fragment of Peloruside A,"A concise synthesis of the C9-C19 fragment of peloruside A that is both highly stereoselective and efficient is described. Achieving an overall yield of 23% over 14 steps, this synthesis not only is high yielding but also involves four chromatography steps. This approach is based on the addition of metal enolates of chiral auxiliary scaffolds generated by either catalytic or stoichiometric amounts of nickel(II) or titanium(IV) Lewis acids.",10.1021/acs.orglett.6b01428,2016-06-03,0.6240751077398757
Tetrahedron,A new synthetic route to -3-oxovalerane and related compounds,,10.1016/s0040-4039(01)82793-3,1966-01-01,0.6240742652112714
Tetrahedron,A totally stereocontrolled route to N-methyl-γ-amino-β-hydroxy acids: Asymmetric synthesis of the amino acid component of hapalosin,,10.1016/s0040-4039(99)01953-x,1999-12-01,0.6240669966550286
Organic Letters,Synthesis of the Bridging Framework of Phragmalin-Type Limonoids,"An efficient synthesis of the octahydro-1H-2,4-methanoindene core of phragmalin-type limonoids, such as xyloccensins O and P, is reported. The success of the synthetic route is predicated on the use of network analysis in the retrosynthetic analysis and a Diels-Alder reaction for the synthesis of a key hydrindanone derivative.",10.1021/ol300647k,2012-04-03,0.6240512968528109
Organic Letters,"Total Synthesis of Chaetoglobin A via Catalytic, Atroposelective Oxidative Phenol Coupling","The first total synthesis of chaetoglobin A (1), which features a chiral axis between two identical highly oxygenated bicyclic cores, was successfully completed in 12 steps from 2,6-dimethoxytoluene. Vanadium-catalyzed oxidative phenol coupling, as a key step, enabled generation of the axial chirality.",10.1021/acs.orglett.8b02183,2018-09-12,0.6240456276286831
Synlett,Synthesis of Donor-Acceptor Substituted Molecular Caltrops: Strategic Use of an AB<sub>3</sub>Synthon Based on a Tetraphenylmethane Core,"Using a tetraphenylmethane based AB3 tecton, a facile synthetic route to donor-acceptor substituted unsymmetrical mole­cular caltrops is described. The former compound was readily prepared in two steps from the cheap commercial dye New Fuchsin.",10.1055/s-2003-42119,2003-01-01,0.6240353223649325
Tetrahedron,A general synthetic route of dihydroagarofuran sesquiterpenoid from α-(−)-santonin,,10.1016/s0040-4039(98)01766-3,1998-10-01,0.6240350423575787
Organic Letters,"Regiospecific, Enantiospecific Total Synthesis of the 12-Alkoxy-Substituted Indole Alkaloids, (+)-12-Methoxy-<i>N</i><sub>a</sub>-methylvellosimine, (+)-12-Methoxyaffinisine, and (−)-Fuchsiaefoline","[reaction: see text] The enantiospecific synthesis of 7-methoxy-d-tryptophan was completed by combination of the Larock heteroannulation process with a Schöllkopf-based chiral auxiliary in good yield. This ester was then employed in the first total synthesis of (+)-12-methoxy-Na-methylvellosimine, (+)-12-methoxyaffinisine, and (-)-fuchsiaefoline in regiospecific, stereospecific fashion in excellent overall yield. The asymmetric Pictet-Spengler reaction and enolate-driven palladium-catalyzed cross coupling processes served as key steps.",10.1021/ol0362212,2003-12-23,0.6240224464777866
Journal of Organic Chemistry,Synthesis of Polyhydroxycyclohexanes and Relatives from (−)-Quinic Acid,"An efficient and versatile strategy for the synthesis of polyhydroxycyclohexanes and related compounds 3-6 is reported. The successful synthesis of these analogues has been achieved from a common intermediate, quinic acid derived lactone 2, rapidly accessible from cheap and commercially available (-)-quinic acid (1) as a chiral template. A practical route involving stereocontrolled epoxide formation and hydrolysis has been developed for the synthesis of 2,3-trans analogues 3 and 4. The preparation of the 2,3-cis analogues 5 and 6 has been realized by diasteroselective oxidation of a 5,6-double bond.",10.1021/jo026692m,2003-02-12,0.6240196494288232
Angewandte Chemie International Edition,A Precisely Bromo‐Functionalized [9]Cycloparaphenylene as a Platform for Late‐Stage Multisite π‐Extension Toward Chiral Nanohoops,"Abstract Selective functionalization of [ n ]cycloparaphenylenes ([ n ]CPPs) has remained a significant synthetic challenge due to their inherent ring strain. In this study, we present the synthesis of a [9]CPP derivative in which bromo groups are orderly introduced at the 2,5‐positions of three benzene rings in the [9]CPP framework, each separated by two phenylene units. The use of our developed Au‐mediated CPP synthetic method enabled efficient and scalable access to the target compound in five steps with an overall yield of 37%. The resulting molecule exhibited phosphorescence at low temperature, arising from the heavy‐atom effect of the bromo substituents. Furthermore, post‐functionalization through Pd‐catalyzed coupling reactions demonstrated multisite π‐extension and afforded a chiral nanohoop exhibiting exceptional chiroptical performance (| g lum | = 0.100).",10.1002/anie.202525108,2025-12-30,0.6240166209591804
Tetrahedron,Four-step convergent synthesis of trans-fused tetracyclic oxane,,10.1016/s0040-4039(99)02102-4,2000-01-01,0.6240139299178846
Angewandte Chemie International Edition,Enantioselective Synthesis of 4‐Hydroxy‐2‐cyclohexenones through a Multicomponent Cyclization,"Three metal cooperation promotes the one-pot selective coupling of a chromium carbene complex, an imide lithium enolate, and a propargylic organomagnesium reagent giving access to novel and densely functionalized 4-allenyl-2-cyclohexenones (see scheme). These useful synthetic intermediates have been prepared through a cyclization process that involves newly reported reaction steps and an unusually high level of asymmetric induction.",10.1002/anie.201004413,2010-11-10,0.6240136568191823
Organic Letters,A Formal Total Synthesis of Dysidiolide,"[structure] A formal total synthesis of the natural product dysidiolide is described. Starting from a Diels-Alder reaction between an enoate and a Rawal diene, the cyclohexenone 4 was synthesized. A subsequent stereospecific methyl cuprate addition established the desired trans configuration in the cyclohexane 3. Wacker oxidation of the pentenyl side chain to the diketone 17 followed by an intramolecular aldol condensation led to the bicyclic enone 2, a key intermediate in a recently reported synthesis of dysidiolide.",10.1021/ol006742e,2000-11-22,0.6240082554151872
Organic Letters,Synthetic Studies toward Anisatin:  A Formal Synthesis of (±)-8-Deoxyanisatin,"[figure: see text] An efficient strategy to construct the congested C-7a quaternary chiral center of anisatin was developed, by way of an Eschenmoser-Claisen rearrangement. Conversion of the resultant amide to Kende's epsilon-lactone intermediate 3 in four steps completed a concise formal synthesis of (+/-)-8-deoxyanisatin (2).",10.1021/ol006918c,2000-12-28,0.6239869834845778
Organic Letters,Salicylaldehyde-Promoted Cobalt-Catalyzed C–H/N–H Annulation of Indolyl Amides with Alkynes: Direct Synthesis of a 5-HT3 Receptor Antagonist Analogue,)-H/N-H bond of indoloamides with alkynes assisted by 8-aminoquinoline is reported for the synthesis of six-membered indololactams. The use of salicylaldehyde as the ligand is crucial for this transformation. The protocol has a broad scope for both alkynes and indoles. Preparing an active Co complex illustrates that salicylaldehyde plays a key role in the C-H activation step. The synthetic applications are proven by the gram-scale reaction and one-step construction of the multicyclic 5-HT3 receptor antagonist.,10.1021/acs.orglett.1c02502,2021-08-27,0.623975983549668
Organic Letters,Total Synthesis of Amphirionin-4,"An expeditious enantioselective total synthesis of amphirionin-4, a remarkably potent promoter of the proliferation of ST-2 cells, has been achieved from (±)-(E)-1,4-hexadien-3-ol by an 8-pot sequence that features the Sharpless kinetic resolution, iodoetherification, and the CBS reduction to install the stereocenters, utilization of four one-pot transformations to streamline the synthetic process, and the Stille coupling reaction at nearly the center of the target molecule to complete the total synthesis.",10.1021/acs.orglett.6b00883,2016-04-12,0.6239342138268162
Tetrahedron,Asymmetric synthesis X: A chiral pyrrolidine synthon for a new approach to the synthesis of alkaloids,,10.1016/s0040-4039(00)95778-2,1987-01-01,0.6239277075266508
European Journal of Organic Chemistry,"Late‐Stage Bromination Enables the Synthesis of Rubrolides B, I, K, and O","A concise and efficient synthesis of the marine natural products rubrolides B, I, K, and O was accomplished in 3–4 steps from commercially available 3,4‐dichloro‐2(5 H )‐furanone. Key steps include: (i) a site‐selective Suzuki cross‐coupling, (ii) a vinylogous aldol condensation, and (iii) a late‐stage bromination. The latter reaction allowed functionalization of the aromatic rings in a highly regioselective fashion, enabling rapid access to the target rubrolides from common precursors.",10.1002/ejoc.201600473,2016-07-06,0.6239267698926517
Organic Letters,Toward the Total Synthesis of Disorazole A<sub>1</sub> and C<sub>1</sub>:  Asymmetric Synthesis of a Masked Southern Segment,"[reaction: see text] A highly convergent asymmetric synthesis of the masked southern segment of the antimitotic agent disorazole A(1) involves a Sonogashira coupling between a C1'-C10' enyne and a suitably protected C11'-C19' vinyl iodide. The central E,Z,Z-triene moiety is masked as a more stable ynediene.",10.1021/ol026468j,2002-08-24,0.623922954566524
Angewandte Chemie International Edition,Total Synthesis of the Tubulin Inhibitor WF‐1360F Based on Macrocycle Formation through Ring‐Closing Alkyne Metathesis,"Key steps in this total synthesis of the antimitotic natural product WF-1360F (3) include the formation of the macrocycle through ring-closing alkyne metathesis and the subsequent conversion of the ensuing alkyne moiety into an E-configured double bond. As illustrated by the synthesis of 4, the macrocyclic vinyl iodide 2 can also serve as a common precursor for the synthesis of side-chain-modified rhizoxin analogues (see scheme; TIPS=triisopropylsilyl).",10.1002/anie.201300576,2013-04-22,0.6239198740766722
Journal of Organic Chemistry,Total Synthesis of Lepadiformine Alkaloids using <i>N</i>-Boc α-Amino Nitriles as Trianion Synthons,"Lepadiformine A, B, and C were synthesized in an enantiomerically pure form using a reductive cyclization strategy. N-Boc α-amino nitriles were deprotonated and alkylated with enantiomerically pure dibromides to afford the first ring. The products were manipulated to introduce phosphate leaving groups, and subsequent reductive lithiation followed by intramolecular alkylation formed the second ring with high stereoselectivity. The third ring was formed by intramolecular displacement of a mesylate by the deprotected amine. Lepadiformine A and B contain a hydroxymethyl group adjacent to the amine. This appendage was introduced in a sequence using a Polonovski-Potier reaction as the key step. The synthetic strategy is stereoselective and convergent and demonstrates the utility of N-Boc α-amino nitriles as linchpins for alkaloid synthesis.",10.1021/jo300161x,2012-03-13,0.6239166687761474
Journal of the American Chemical Society,Total Synthesis of Maoecrystal V: Early-Stage C–H Functionalization and Lactone Assembly by Radical Cyclization,A total synthesis of the unusual ent-kaurane maoecrystal V is described. The synthesis strategy features a counterintuitive early disconnection of the lactone subunit to a polycyclic enol ether intermediate in order to preserve the central tetrahydrofuran ring until the beginning stages of the synthesis. This strategy enables an application of C-H functionalization at the early phase of the synthesis during the construction of a dihydrobenzofuran intermediate.,10.1021/ja408231t,2013-09-19,0.6239163073082761
Synthesis,First Total Synthesis of Lippialactone and Its C9 Epimer,This paper describes the first total synthesis of bioactive lippialactone and C9- epi -lippialactone adopting Keck asymmetric allylation/Barbier allylation and olefin cross-metathesis as the key steps.,10.1055/s-0033-1340314,2013-12-06,0.6239087244139674
Tetrahedron,An efficient stereoselective route to the construction of tricyclic core structure towards the synthesis of the sesquiterpenes of the seco-prezizaane family,,10.1016/j.tetlet.2011.02.054,2011-02-18,0.6239007918970221
Tetrahedron,"The design of efficient and selective routes to a key 1,4-cis-substituted cyclohexylamide intermediate",,10.1016/j.tetlet.2010.03.083,2010-03-30,0.6238997498245054
Tetrahedron,An efficient high-speed synthetic route to amino-substituted thiazolidinone libraries,,10.1016/s0040-4039(98)01592-5,1998-10-01,0.6238942124023453
Journal of Organic Chemistry,Total Synthesis of Virgatolide B via Exploitation of Intramolecular Hydrogen Bonding,"A full account of the enantioselective total synthesis of virgatolide B is reported. Key features of the synthesis include an sp(3)-sp(2) Suzuki-Miyaura cross-coupling of a β-trifluoroboratoamide with an aryl bromide, regioselective intramolecular carboalkoxylation, and a 1,3-anti-selective Mukaiyama aldol reaction. Intramolecular hydrogen bonding governed the regioselectivity of the key spiroketalization step, affording the natural product as a single regioisomer.",10.1021/jo5008527,2014-05-16,0.6238820884767107
Angewandte Chemie International Edition,Total Synthesis of (+)‐Azaspiracid‐1. Part I: Synthesis of the Fully Elaborated ABCD Aldehyde,"Has aspirations: The total synthesis of (+)-azaspiracid-1 has been realized. The ABCD fragment was synthesized in 20 linear steps and 16 % overall yield through the enantioselective syntheses of the AB sulfone and the CD aldehyde, their coupling by a sulfone anion addition, and a thermodynamically controlled bis(spiroketalization) event. The E, FG, and HI ring fragments were synthesized enantioselectively and then coupled by using aldol methodology. Finally, a complex addition of the anion of the anomeric EFGHI sulfone to the ABCD aldehyde completed the synthesis in 26 linear steps and 2.7 % yield.",10.1002/anie.200701515,2007-06-01,0.623872835910717
Organic Letters,Total Synthesis and Stereochemical Revision of Acortatarins A and B,"A first total synthesis of acortatarins A, B, and an enantiomer of the proposed structure of acortatarin B is described by using readily available d-sugars. This convergent total synthesis revealed the revision of the absolute configuration of acortatarin A and structural revision of acortatarin B. The key steps involved are regioselective epoxide opening with deprotonated 2,5-disubstituted pyrrole and spiroketalization.",10.1021/ol202121k,2011-09-28,0.6238703774522655
Journal of Organic Chemistry,"Iridium-Catalyzed Asymmetric Hydrogenation of Heteroaromatics with Multiple N Atoms via Substrate Activation: An Entry to 4,5,6,7-Tetrahydropyrazolo[1,5-<i>a</i>]pyrimidine-3-carbonitrile Core of a Potent BTK Inhibitor","High Resolution Image Download MS PowerPoint Slide The chiral 4,5,6,7-tetrahydropyrazolo[1,5- a ]pyrimidine is the key core skeleton of potent Bruton’s tyrosine kinase (BTK) inhibitor Zanubrutinib, and the catalyst-controlled asymmetric hydrogenation of planar multinuclear pyrimidine heteroarenes with multiple N atoms could provide an efficient route toward its synthesis. Owing to the strong aromaticity and poisoning effect toward chiral transition metal catalyst, asymmetric hydrogenation of pyrazolo[1,5- a ]pyrimidines with multiple nitrogen atoms is still a challenge for synthesizing the chiral 4,5,6,7-tetrahydropyrazolo[1,5- a ]-pyrimidine. Herein, an efficient iridium-catalyzed asymmetric hydrogenation of pyrazolo[1,5- a ]pyrimidines has been developed using substrate activation strategy, with up to 99% ee. The decagram scale synthesis further demonstrated the potential and promise of this procedure in the synthesis of Zanubrutinib. In addition, a mechanistic study indicated that the hydrogenation starts with 1,2-hydrogenation.",10.1021/acs.joc.3c02396,2024-03-11,0.6238628190614264
Tetrahedron,Synthesis of d-ribo-C18-phytosphingosine from d-glucosamine via the d-allosamine derivatives as key intermediates,,10.1016/s0040-4039(02)00919-x,2002-07-01,0.6238605522057141
Tetrahedron,"Stereoselective synthesis of N-Boc-O-benzyl-(4S,5S)-5-amino-4-hydroxy-6-phenylhexanoic acid, the hydroxyethylene isosteric moiety of potent HIV-1 protease inhibitor",,10.1016/s0040-4039(00)85991-2,1991-04-01,0.6238571987557133
Organic Letters,A New Nucleophilic Addition/Ring-Closure Sequence. Enantioselective Synthesis of 3-Deoxy-8-oxatropanes,"[reaction: see text] A study of new nucleophilic addition/ring-closure (NARC) sequences has resulted in the development of a stereoselective synthetic route to 3-deoxy-8-oxatropanes. The new sequences consisted of either a syn or anti aldol addition, employing an omega-alkenoyl sultam, followed by two-step bicyclic ring construction involving, consecutively, ring-closing metathesis and intramolecular oxymercuration.",10.1021/ol036404o,2004-02-27,0.6238570076818692
Synlett,"Stereoselective Synthesis of Methyl Spongoate, a New Steroid with Potent Antitumor Activities","The stereoselective synthesis of methyl spongoate, a naturally occurring new steroid derivative with an unusual C-20 methoxycarbonyl group and potent antitumor activities, was achieved starting from the commercially available pregnenolone acetate in 11% overall yield.",10.1055/s-0029-1218567,2009-12-11,0.6238558756479051
Synthesis,Scalable Synthesis of 4-Substituted 5-Bromo-6-methylpyrimidines,"Small halogenated heteroaromatic ring systems are valuable monomers, which can enable rapid access to novel and desirable chemical space, in part because of their ability to participate in established cross coupling chemistry such as the Heck, Stille, and Suzuki reactions. Described is a practical, scalable synthetic route towards the construction of a diverse array of 4-substituted 5-bromo-6-methylpyrimidine monomers.",10.1055/s-0030-1259976,2011-03-31,0.6238534908182307
Organic Process Research & Development,Large-Scale Synthesis of a Selective Inhibitor of the Norepinephrine Transporter: Mechanistic Aspects of Conversion of Indolinone Diol to Indolinone Aminoalcohol and Process Implications,"Development of a scalable synthesis of WAY-315193 is described. Use of LiHMDS as a base and Ti(O- i -Pr) 4 as a Lewis acid was optimal for efficient and reproducible addition of indolinone anion to epoxyalcohol. Conversion of indolinone diol to indolinone aminoalcohol was achieved via monotosylation−methylamination. The possibility of selective formation of the amidine side product, as well as its utilization for alternative selective preparation of the target aminoalcohol, was demonstrated.",10.1021/op900141r,2009-08-17,0.6238353679667593
Tetrahedron,"A stereoselective synthesis of (E)-1-halo-6,6-dimethyl-2-hepten-4-yne: a key intermediate for terbinafine",,10.1016/s0040-4039(00)00511-6,2000-05-01,0.6238346951565766
Tetrahedron,"Corrigendum to “A stereoselective synthesis of (E)-1-halo-6,6-dimethyl-2-hepten-4-yne: a key intermediate for terbinafine”",,10.1016/s0040-4039(00)01317-4,2000-10-01,0.6238346951565766
Journal of Organic Chemistry,Protecting Group Free Synthesis of 6-Substituted Naphthols and Binols,"A straightforward route for the preparation of 6-substituted naphthols and 6,6'-disubstituted binols (binol = 2,2'-dihydroxy-1,1'-binaphthyl) is presented. The synthesis has been accomplished by a one-step procedure starting from 6-bromo derivatives via direct lithiation with n-BuLi, followed by the addition of several electrophiles. This C-C functionalization has been successfully achieved with iodomethane, 3-methoxybenzaldehyde, benzophenone, methyl-2-methylbenzoate, methylbenzoate, dimethyl carbonate, ethyl 2-chloro-2-oxoacetate, and 2,2-dimethyloxirane (E). This reactivity offers a useful protecting group free synthetic protocol, toward chiral disubstituted 6,6'-binols with configuration retention of the binol moiety.",10.1021/jo1025892,2011-03-08,0.623833081552375
Synlett,"Sharpless Asymmetric Dihydroxylation on α,β-Unsaturated Diazoketones: A New Entry for the Synthesis of Disubstituted Furanones","The synthesis of enantiomerically pure 4,5-disubstituted 2-furanones is accomplished in three steps from aldehydes. The steps involve a highly enantioselective Sharpless asymmetric dihydroxylation of α,β-unsaturated diazoketones, followed by a photochemical Wolff rearrangement.",10.1055/s-0036-1590977,2017-08-15,0.6238087058431391
Journal of Organic Chemistry,"Total Synthesis of Ellipticine Quinones, Olivacine, and Calothrixin B","A direct route to the synthesis of biologically active ellipticine quinones, olivacine, and calothrixin B is described. The prominent key steps involved are Friedel-Crafts hydroxyalkylation followed by oxidation and directed ortho-lithiation reactions of readily available indole-2-carboxylate esters with appropriately substituted pyridine and quinoline carboxaldehydes.",10.1021/jo402593w,2013-12-28,0.6237896358965258
Organic Process Research & Development,Adagrasib’s Second-Generation Synthesis: Transitioning from Route Scouting to Optimization,"High Resolution Image Download MS PowerPoint Slide Process optimization details are disclosed following the completion of process design for a second-generation manufacturing route of adagrasib. Key objectives for development included control of difficult-to-purge impurities in the key starting materials (KSMs), enhanced scalability of the KSM, improved pyrimidone formation of the core, increased robustness of oxidation, enhanced stability of the step 3 intermediate, removal of the halogenated solvent in the fourth step, and implementation of single crystallization of the final API. These improvements led to more efficient production of adagrasib and a further reduction in the cost of goods by approximately 50%.",10.1021/acs.oprd.4c00024,2024-04-10,0.6237797612971927
European Journal of Organic Chemistry,"Bisannulation of 2,3‐Dichloro‐1,4‐naphthoquinone with <i>o</i>‐Nitrophenylacetic Acid Derivatives: A Succinct Synthesis of the ABCD Ring System of Alpkinidine","Abstract Three bisannulation strategies have been used to rapidly construct pentacyclic benzo‐fused pyrrolo[4,3,2‐ mn ]acridines, similar to several biologically active natural products. The key steps involve Michael substitution of 2,3‐dichloro‐1,4‐naphthoquinone with o ‐nitrophenylacetic acid derivatives, followed by domino amino‐Michael substitutions/cyclisations. The most efficient of these syntheses provided a model compound ( 1 ) including the ABCD ring‐system of alpkinidine, in just three steps and 55 % overall yield.",10.1002/ejoc.201300227,2013-04-19,0.6237583825564544
Journal of the American Chemical Society,Total Synthesis of the Ramoplanin A2 and Ramoplanose Aglycon,"A convergent total synthesis of the ramoplanin A2 and ramoplanose aglycon is disclosed. Three key subunits composed of residues 3-9 (heptapeptide 15), pentadepsipeptide 26, and pentapeptide 34 (residues 10-14) were prepared, sequentially coupled, and cyclized to provide the 49-membered depsipeptide core of the aglycon. Key to the preparation of the pentadepsipeptide 26 incorporating the backbone ester was the asymmetric synthesis of an orthogonally protected L-threo-beta-hydroxyasparagine and the development of effective and near-racemization free conditions for esterification of its hindered alcohol (EDCI, DMAP, 0 degrees C). The coupling sites were chosen to maximize the convergency of the synthesis including that of the three subunits, to prevent late stage racemization of carboxylate-activated phenylglycine-derived residues, and to enlist beta-sheet preorganization of an acyclic macrocyclization substrate for 49-membered ring closure. As such, macrocyclization at the chosen Phe(9)-D-Orn(10) site may benefit from both beta-sheet preorganization as well as closure at a D-amine terminus. Deliberate late stage incorporation of the subunit bearing the labile depsipeptide ester and a final stage Asn(1) side chain introduction provides future access to analogues of the aglycons which themselves are reported to be equally potent or more potent than the natural products in antimicrobial assays.",10.1021/ja020237q,2002-04-18,0.6237533178013039
European Journal of Organic Chemistry,Synthesis of the Pentacyclic Framework of the Alkaloid Tronocarpine,"Abstract A short and efficient synthesis of the pentacyclic core of the indole alkaloid tronocarpine is described. The synthetic pathway involves several easily accomplished steps, including a radical oxidative aromatic substitution reaction on the N ‐ tert ‐butoxycarbonyl‐protected tryptamine and a xanthate, a 1,4–1,2‐nucleophilic addition between a 2,3‐disubstituted indole and an α,β‐unsaturated aldehyde, and a Ti‐mediated Dieckmann condensation. This report represents a significant advance in the quest for the first total synthesis of tronocarpine.",10.1002/ejoc.201301388,2013-11-22,0.6237497805248369
Tetrahedron,The first chiral version of Jackson N-benzyl-N-tosylaminoacetal cyclization. A new enantioselective total synthesis of 1-s-(-)-salsoiidine,,10.1016/0040-4039(95)01975-n,1995-12-01,0.6237452636831233
Organic Letters,Asymmetric Synthesis of Functionalized<i>trans-</i>Cyclopropoxy Building Block for Grazoprevir,"A practical and asymmetric synthesis of a functionalized trans -cyclopropoxy building block for the preparation of the HCV NS3/4a protease inhibitor grazoprevir is reported. Intramolecular S N 2 displacement–ring closure, followed by a Baeyer–Villiger oxidation, yields the desired trans -cyclopropanol with full control of diastereoselectivity. A terminal alkyne is then effectively installed using LiNH(CH 2 ) 2 NEt 2 . Starting from ( S )-epichlorohydrin, the cyclopropoxy building block is prepared in 51% overall yield with >99.8% optical purity without isolation of any intermediates.",10.1021/acs.orglett.7b02867,2017-10-20,0.6237353163526521
Journal of Organic Chemistry,Synthesis of a Tristearoyl Lipomannan via Preactivation-Based Iterative One-Pot Glycosylation,"A convergent and efficient strategy was developed for the synthesis of lipomannan (LM), useful for vaccine development. Thioglycosides were employed as glycosyl donors to construct two key pseudotrisaccharide and tetramannose intermediates through preactivation-based glycosylation strategy. These building blocks were then successfully coupled to form the LM core, which was lapidated, phospholipidated, and finally globally deprotected to afford the target molecule. The intermediate LM core involved in this synthesis contained orthogonal protections, which would facilitate its variable modifications for the preparation of other complex LM derivatives and for the synthesis of LM conjugates as LM-based vaccines.",10.1021/jo4021979,2013-11-22,0.6237316090370104
Tetrahedron,Studies directed toward the total synthesis of kabiramide C: Asymmetric synthesis of the C1–C19 fragment,An efficient synthesis of the C1C6 aliphatic fragment 3 and its coupling to the C7C19 fragment 4 of kabiramide C is described. Key transformations include a TiCl4 promoted condensation between aldehyde 5 and crotylsilane (R)-6 and a Barton-McCombie deoxygenation of the homoallylic alcohol 9 to set the stereochemical array.,10.1016/s0040-4039(98)01300-8,1998-08-01,0.6237304582770687
Organic Letters,Biomimetic Synthesis and Biological Evaluation of Aplidiopsamine A,"The first total synthesis of Aplidiopsamine A, a rare 3H-pyrrolo[2,3-c]quinoline alkaloid from the Aplidiopsis confluata, has been achieved following the proposed biosynthesis. This biomimetic synthesis requires only five steps and proceeds in 20.8% overall yield. Biological evaluation across large panels of discrete molecular targets identified that Aplidiopsamine A is a highly selective PDE4 inhibitor, a target for numerous CNS disorders.",10.1021/ol3024665,2012-10-29,0.6237294656560697
Synlett,Asymmetric Total Synthesis of (+)-Minfiensine by an Asymmetric Cascade Cyclization Strategy,"The Strychnos alkaloid minfiensine and a series of akuammiline alkaloids, such as vincorine, aspidophylline A, and picrinine, possess a common core skeleton, a 4a,9a-heterocycle-fused tetrahydrocarbazole. Efficient construction of this core structure in a highly enantioselective manner would facilitate the total synthesis of these alkaloids. In this article, we briefly summarize the established strategies for obtaining this core structure, together with the corresponding total-synthesis routes, and we describe our own effort on the development of a new strategy, the asymmetric cascade dearomative cyclization, for the efficient total synthesis of (+)-minfiensine.",10.1055/s-0036-1589075,2017-08-25,0.6237236005259641
Angewandte Chemie International Edition,Enantioselective Cooperativity Between Intra‐Receptor Interactions and Guest Binding: Quantification of Reinforced Chiral Recognition,"Call in the reinforcements: Intra-receptor noncovalent interactions can enantioselectively cooperate with guest binding, thus triggering chiral discrimination. Such cooperativity is described and quantified for a simple synthetic system wherein an intra-receptor hydrogen bond cooperates with a CH–π interaction exclusively formed with the D enantiomer of the guest, thus exemplifying reinforced chiral recognition (see picture).",10.1002/anie.201103970,2011-09-20,0.6237209178927737
Synthesis,"Efficient Synthesis of Pyrido[3,2-c]coumarins via Silver Nitrate Catalyzed Cycloisomerization and Application to the First Synthesis of Polyneomarline C","Herein, we report an efficient method for the synthesis of the pyrido[3,2-c]coumarin scaffold, one of the privileged heterocycle-fused coumarin scaffolds, via a AgNO3-catalyzed cycloisomerization of 4-(propynylamino)coumarins obtained from diverse 4-hydroxycoumarins. This concise method affords pyrido[3,2-c]coumarin analogues bearing diverse substituents on the benzene or pyridine ring in moderate to good yields. Moreover, this methodology was extended to the facile synthesis of polyneomarline C, a natural pyrido[3,2-c]coumarin derivative isolated from the Chinese herbal medicine Polyalthia nemoralis A. DC., in three steps and in 26% overall yield from the known 4-hydroxycoumarin.",10.1055/s-0037-1610730,2019-09-30,0.6236962112923672
Journal of the American Chemical Society,Total Synthesis of (−)-Nakadomarin A,"A short and highly stereoselective synthesis of (-)-nakadomarin A has been developed using combinations of catalyst-controlled bond formations, one-pot multistep procedures, and powerful route-shortening reaction cascades. Several unprecedented chemical transformations were developed, including a highly Z-selective, eight-membered-ring-forming intramolecular Julia-Kocienski reaction, a highly diastereoselective intramolecular furan/iminium ion cyclization, and a sulfonic acid-controlled Z-selective macrocyclic ring-closing metathesis. In conjunction with a diastereoselective nitro olefin Michael addition under bifunctional organocatalysis and a nitro-Mannich/lactamization cascade, these transformations allowed the construction of this architecturally complex natural product in significant quantities in 12 steps (longest linear sequence) from commercially available starting materials.",10.1021/ja908399s,2009-11-02,0.6236943013088113
Organic Letters,Biomimetic Total Synthesis of Paeoveitol,"A highly stereocontrolled synthesis of paeoveitol has been developed in 26% yield, in 7 steps from commercially available materials. The synthetic strategy was inspired primarily by the biogenetic hypothesis and was enabled by hetero-Diels-Alder cycloaddition to construct the target molecular framework.",10.1021/acs.orglett.6b02228,2016-08-29,0.6236898802780738
Organic Letters,A Photorearrangement To Construct the ABDE Tetracyclic Core of Palau’amine,"A synthesis of the ABDE tetracyclic carbon core of palau'amine was achieved in 9 steps from commercial materials. The core's most notable feature, a highly strained trans cyclopenta[ c]pyrrolidine, was obtained in high yield using a ring contraction strategy starting from a much less strained trans bicyclic lactam derivative that is accessible in only 7 steps.",10.1021/acs.orglett.8b00819,2018-04-18,0.6236856612783145
Journal of the American Chemical Society,Total Synthesis of (±)-Communesin F via a Cycloaddition with Indol-2-one,A concise total synthesis of (±)-communesin F has been completed in 15 linear steps from 4-bromotryptophol in an overall yield of 6.7%. A key step features the cycloaddition of indol-2-one with 3-(2-azidoethyl)-4-bromoindole and facilitates the rapid construction of the lower aminal-containing tetracyclic core of the natural product.,10.1021/ja307277w,2012-09-14,0.6236823689166204
Organic Letters,Asymmetric Total Synthesis and Absolute Configuration Determination of (−)-Verrupyrroloindoline,"The first asymmetric total synthesis of (-)-verrupyrroloindoline (20% overall yield in 6 steps) is described. The short approach was enabled by Buchwald's Cu(II)-catalyzed asymmetric conjugate reduction, DMDO-triggered one-pot four-step tandem reaction, and the first amide-selective Ir-catalyzed direct reduction of β-carboethoxy tertiary lactam. Along with the total synthesis, the absolute configuration of natural verrupyrroloindoline was determined as 7 R,10 R,11 R.",10.1021/acs.orglett.8b01579,2018-07-03,0.6236815762858324
Synlett,A New Synthesis of 8-Oxabicyclo[3.2.1]octan-2-one and Its Use for the Preparation of Cycloheptane Annulated Furans,"Two novel syntheses of 8-oxabicyclo[3.2.1]octan-2-one are described, making this key intermediate readily available in preparative amounts. On chain elongation with various oxophosphonates this compound is converted to α,β-unsaturated ketones, which, on treatment with BF3˙OEt2, cyclize to furanocycloheptanols with a substitution pattern not reported previously.",10.1055/s-0029-1218371,2009-11-18,0.6236492757390381
Tetrahedron,2-hydroxymethyl-4-phenylthio-1-butene as a key compound for total synthesis of acyclic terpenoids,,10.1016/0040-4039(81)80145-1,1981-01-01,0.6236310161578027
Angewandte Chemie International Edition,Total Synthesis of Belizentrin Methyl Ester: Report on a Likely Conquest,"The assigned structure of the dinoflagellate-derived toxin belizentrin was prepared by total synthesis in form of the corresponding methyl ester for stability reasons. The successful route features an unusual solution for the preparation of a recalcitrant ylide on a C-glycosidic segment; moreover, it involves an asymmetric hetero-Diels-Alder reaction en route to the tertiary hemiacetal substructure, a Negishi cross-coupling of two elaborate building blocks, and a macrocyclization based on an intramolecular aminolysis of a spirolactone. A modified Kocienski olefination ultimately allowed the polyol side chain to be attached to the macrocycle although this transformation faced the exceptional base sensitivity of this polyunsaturated target compound.",10.1002/anie.201805125,2018-06-01,0.6236300115135245
Synlett,A Convergent Synthesis of Tetracyclic Indole Compounds by a Palladium-Catalyzed Cross-Coupling and Tandem Cyclization Reaction,"Abstract A new strategy for the convergent synthesis of the ABCD ring system of indole terpene alkaloids has been developed based on a Sonogashira coupling of an o-iodoaniline (the A ring) with an alkyne bearing the D ring. After a tandem palladium-catalyzed cyclization, the tetracyclic ABCD ring structure found in the terpene indole alkaloids was obtained in good yield.",10.1055/s-0042-1751396,2022-12-19,0.6236164887967437
Angewandte Chemie International Edition,A Synthesis of the Chlorosulfolipid Mytilipin A via a Longest Linear Sequence of Seven Steps,"Magnificent seven: The chlorosulfolipid mytilipin A was synthesized in racemic form in seven steps and in enantioenriched form in eight steps. Key transformations include a highly diastereoselective bromoallylation of a sensitive α,β-dichloroaldehyde, a kinetic resolution of a vinyl epoxide, a convergent and highly Z-selective alkene cross-metathesis, and a chemoselective and diastereoselective dichlorination of a complex diene.",10.1002/anie.201304565,2013-08-08,0.6236120326818578
Journal of Organic Chemistry,"Total Syntheses of Murrayamine E, I, and K","We describe efficient synthetic routes to murrayamine A (mukoenine C), O-methylmurrayamine A, mahanine, O-methylmahanine, and murrayamine D and the first total syntheses of murrayamine E, I, and K. Key steps are a palladium-catalyzed construction of the carbazole framework and an annulation of the pyran ring, which is either catalyzed by phenylboronic acid or promoted by a Lewis acid.",10.1021/acs.joc.5b00630,2015-04-27,0.6236104011664516
Tetrahedron,Synthesis of new acromelic acid congeners: novel neuroexcitatory amino acids acting on glutamate receptor,,10.1016/s0040-4039(00)78802-2,1991-06-01,0.623608342660968
Synthesis,Synthesis of Spirocyclopropane Scaffolds: A Review,"Abstract This review highlights different synthetic strategies for preparing a spirocyclopropane moiety, covering the literature from 1989 to 2024. The spirocyclopropane moiety is a structural scaffold that is used to access synthetic libraries of highly functionalized spirocarbo- and heterocyclic molecules. The review showcases different routes for the synthesis of spirocyclopropanes that utilize distinct precursors and methodologies, including cascade reactions, cyclopropanation, Michael-initiated ring closure (MIRC), and one-pot and multicomponent synthesis. These discussions are organized around the oxindole core, which include isatin, oxindole, 3-chlorooxindole, and 3-alkenyl oxindoles. Additionally, this review explores various ylides and other techniques. The goal of this review is to provide a background for synthetic chemistry researchers to develop new ideas and novel synthetic routes to spirocyclopropanes. 1 Introduction 2 Synthesis of Spirocyclopropanes from 3-Chlorooxindole Derivatives 3 Synthesis of Spirocyclopropanes from Isatin Derivatives 3.1 Synthesis of Spirocyclopropanes from Alkylidene Oxindole Derivatives 3.2 Synthesis of Spirocyclopropanes from Diazooxindole Compounds 4 Synthesis of Spirocyclopropanes from 1,3-Diones 5 Synthesis of Spirocyclopropanes from N-Ylides 6 Synthesis of Spirocyclopropanes from S-Ylides 7 Miscellaneous Syntheses of Spirocyclopropanes 8 Conclusion 9 List of Abbreviations",10.1055/s-0043-1775471,2025-06-04,0.62360191333814
Tetrahedron,Grignard reagent-promoted selective ring expansion and alkylation of formyl borneol and isoborneol: a new route to highly substituted cyclopentanes,,10.1016/j.tetlet.2005.01.102,2005-02-05,0.6236009878723415
Journal of Organic Chemistry,"Straightforward Methodology for the Enantioselective Synthesis of Benzo[<i>a</i>]- and Indolo[2,3-<i>a</i>]quinolizidines","An enantioselective two-step route to substituted benzo[a]- and indolo[2,3-a]quinolizidines has been developed. It consists of (i) a stereoselective cyclocondensation of a racemic or prochiral delta-oxo(di)ester with either (S)-(3,4-dimethoxyphenyl)alaninol or (S)-tryptophanol in a process involving a dynamic kinetic resolution and/or the differentiation of enantiotopic or diastereotopic ester groups, and (ii) a subsequent stereocontrolled cyclization on the aromatic ring taking advantage of the masked N-acyl iminium ion present in the resulting oxazolopiperidone lactams.",10.1021/jo070539g,2007-06-05,0.623600008965568
Angewandte Chemie International Edition,Genetic Engineering in Combination with Semi‐Synthesis Leads to a New Route for Gram‐Scale Production of the Immunosuppressive Natural Product Brasilicardin A,"Brasilicardin A (1) consists of an unusual anti/syn/anti-perhydrophenanthrene skeleton with a carbohydrate side chain and an amino acid moiety. It exhibits potent immunosuppressive activity, yet its mode of action differs from standard drugs that are currently in use. Further pre-clinical evaluation of this promising, biologically active natural product is hampered by restricted access to the ready material, as its synthesis requires both a low-yielding fermentation process using a pathogenic organism and an elaborate, multi-step total synthesis. Our semi-synthetic approach included a) the heterologous expression of the brasilicardin A gene cluster in different non-pathogenic bacterial strains producing brasilicardin A aglycone (5) in excellent yield and b) the chemical transformation of the aglycone 5 into the trifluoroacetic acid salt of brasilicardin A (1 a) via a short and straightforward five-steps synthetic route. Additionally, we report the first preclinical data for brasilicardin A.",10.1002/anie.202015852,2021-03-26,0.6235778042214537
Tetrahedron,Novel alkaline hydrolysis of triaminocyclopropenium ion. new route to diaminocyclopropenone and diaminocyclopropenethione,,10.1016/s0040-4039(01)96160-x,1973-01-01,0.6235742935917121
Organic Process Research & Development,"Improved Synthetic Procedures for 4,7,2‘,7‘-Tetrachloro- and 4‘,5‘-Dichloro-2‘,7‘-dimethoxy-5(and 6)-carboxyfluoresceins","Literature syntheses of 4,7,2‘,7‘-tetrachloro-5(and 6)-carboxy-fluorescein (“5 and 6 TET”) 1 and 4‘,5‘-dichloro-2‘,7‘-dimethoxy-5(and 6)-carboxyfluorescein (“5 and 6 JOE”) 2 are reviewed, and new, preparatively useful methods are presented. A three-step synthesis of 1 was developed, which proved to be more efficient than the published seven step synthesis of this compound. The published synthesis of 2 also proved difficult to reproduce, and a better workup of the key intermediate 2-chloro-4-methoxy resorcinol was devised. Isolation of purified single isomers of both dyes is described.",10.1021/op000292o,2000-11-11,0.6235732575895617
Angewandte Chemie International Edition,Inside Back Cover: Fragment‐Based Discovery of a Dual pan‐RET/VEGFR2 Kinase Inhibitor Optimized for Single‐Agent Polypharmacology (Angew. Chem. Int. Ed. 30/2015),"The inhibitory powers of a next-generation inhibitor were carefully balanced so that it is equally potent on the RET kinase and VEGFR2. In their Communication on page 8717 ff., H.-y. Li, M. Santoro, et al. report the optimization of a dual inhibitor for the treatment of RET-driven malignancies through synergistic medicinal chemistry. The inhibitor is capable of simultaneously treating the parenchyma (RET) and stroma (VEGFR2) at the same therapeutic dose.",10.1002/anie.201505540,2015-07-03,0.6235712237359399
European Journal of Organic Chemistry,Total Synthesis of Marine Alkaloid Hyellazole and its Derivatives,"The total synthesis of the naturally occurring marine alkaloids hyellazole and chlorohyellazole was attempted from the corresponding easily accessible 2‐methyl‐1‐ketotetrahydrocarbazoles obtained through the Japp–Klingemann reaction, followed by Fischer indole cyclization and subsequent Grignard coupling with phenylmagnesium bromide. Grignard coupling with 2‐methyl‐1‐ketotetrahydrocarbazole unfortunately led directly to 2‐methyl‐1‐phenylcarbazole through dehydration followed by aromatization through aerial oxidation, but application of the same reaction conditions to 6‐chloro‐2‐methyl‐2,3,4,9‐tetrahydro‐1 H ‐carbazol‐1‐one, with careful treatment, led to the isolation of 6‐chloro‐2‐methyl‐1‐phenyl‐4,9‐dihydro‐3 H ‐carbazole. However, selenium dioxide oxidation of this dihydrochloro derivative led to the formation of 6‐chloro‐2‐methyl‐1‐phenyl‐9 H ‐carbazole. A different route was then adopted: a suitably substituted aromatic amine was used to establish the substitution pattern of the required carbazole derivative with a bromo group at C‐1, and the required phenyl group at the 1‐postion was then attached through Suzuki–Miyaura cross‐coupling to furnish hyellazole.",10.1002/ejoc.201800187,2018-03-15,0.6235675472447489
Journal of Organic Chemistry,"Accessing 1,8-Naphthyridone-3-carboxylic Acid Derivatives and Application to the Synthesis of Amfonelic Acid","1,8-Naphthyridone-3-carboxyl is the core structure of several on-market antibacterial drugs. It has prompted significant interest from the synthetic community. Here, we report a practical synthesis of diversely functionalized 1,8-naphthyridone-3-carboxylic acid derivatives starting from readily available and inexpensive nicotinic acid derivatives. All key steps have been optimized. Furthermore, the usefulness of this protocol has been exemplified by the first synthesis of amfonelic acid.",10.1021/acs.joc.4c00415,2024-04-11,0.6235642108907846
Synthesis,Concise Total Synthesis of (+)-Disparlure and its trans-Isomer Using Asymmetric Organocatalysis,The efficient enantioselective synthesis of (+)-disparlure and its trans-isomer is described. This approach involves tandem asymmetric organocatalytic α-aminoxylation-allylation of an aldehyde and olefin cross metathesis using Grubbs' catalyst as key steps.,10.1055/s-0029-1216855,2009-05-29,0.6235587608545151
Journal of Organic Chemistry,Synthesis of (±)-<i>cis</i>-Clavicipitic Acid by a Rh(I)-Catalyzed Intramolecular Imine Reaction,"A new and short synthesis of racemic cis-clavicipitic acid was achieved by taking advantage of the double nucleophilic character of indole-4-pinacolboronic ester. Key to the success of the synthesis were an efficient and selective C-3 indole Friedel-Crafts alkylation and the development of an unprecedented intramolecular rhodium-catalyzed 1,2-addition of an aryl pinacolboronic ester to an unactivated imine.",10.1021/jo500245s,2014-03-07,0.6235539043517845
Tetrahedron,A novel route to formamides and their derivatives. Reduction of isocyanates via hydrosilylation catalyzed by palladium,,10.1016/s0040-4039(01)87223-3,1973-01-01,0.6235336218167301
Synthesis,Oxabicyclo[3.2.1]oct-6-enes as Templates for the Stereoselective Synthesis of Polypropionates: Total Synthesis of Callystatin A and C19-<i>epi</i>-Callystatin A,The total synthesis of the polyketide natural product callystatin A and its novel analog C19-epi-callystatin A is described. Our strategy features the use of an enantiomerically pure oxabicyclo[3.2.1]oct-6-ene as a template for the stereocontrolled preparation of the C15-C21 polypropionate region.,10.1055/s-2002-34386,2002-09-26,0.6235292887071516
Organic Letters,Total Synthesis of Virgatolide B,"The first total synthesis of the benzannulated spiroketal virgatolide A is presented. Key features include sp(3)-sp(2) Suzuki coupling of an enantiomerically enriched β-trifluoroboratoamide and an aryl bromide, regioselective intramolecular carboalkoxylation, and a 1,3-anti-selective Mukaiyama aldol reaction followed by global deprotection/cyclization with regioselectivity governed by internal hydrogen bonding.",10.1021/ol402191t,2013-08-19,0.6235127389676789
Organic Letters,Transition-Metal-Catalyzed Synthesis of Aspergillide B: An Alkyne Addition Strategy,A catalytic enantioselective formal total synthesis of aspergillide B is reported. This linchpin synthesis was enabled by the development of new conditions for Zn-ProPhenol catalyzed asymmetric alkyne addition. This reaction was used in conjunction with ruthenium-catalyzed trans-hydrosilylation to affect the rapid construction of a late-stage synthetic intermediate of aspergillide B to complete a formal synthesis of aspergillide B in a highly efficient manner.,10.1021/ol300200m,2012-02-22,0.6234948650888302
European Journal of Organic Chemistry,"The First Total Synthesis of Solomonsterol B, a Marine Pregnane X Receptor Agonist","Abstract A concise route to the pregnane X receptor (PXR) agonist solomonsterol B, a natural product isolated from the marine sponge Theonella swinhoei , has been developed starting from commercially available hyodeoxycholic acid. The synthesis features a one‐carbon side chain degradation and the refunctionalization of the A and B rings to install the desired trans junction and the two hydroxy groups at C2 and C3 in a trans relationship. The protocol proceeded with good yields (10 % over 13 steps), also allowing the preparation of a side chain‐modified derivative useful for a preliminary structure–activity relationship on PXR. The pharmacological characterization of solomonsterol B demonstrated that this compound was a PXR agonist in a transactivation assay, and when it was incubated with liver cells, it increased the expression of PXR‐regulated genes. These data support the development of sponge steroids as PXR ligands endowed with therapeutic potential.",10.1002/ejoc.201200619,2012-07-19,0.6234913973542766
Organic Letters,Synthesis of Pyrrolidine <i>C</i>-Nucleosides via Heck Reaction,[figure: see text] A novel method for the synthesis of pyrrolidine C-nucleosides has been developed. The key step of the synthesis is the palladium(0)-mediated coupling of a disubstituted N-protected 2-pyrroline and 5-iodouracil. C-Nucleoside 14 and its N-methyl derivative 15 can easily be converted to the corresponding phosphoramidite building blocks for DNA synthesis.,10.1021/ol007029s,2001-01-17,0.6234860847156537
Organic Letters,Toward the Total Synthesis of the Brasilinolides: Construction of a Differentially Protected C20−C38 Segment,"An efficient, convergent synthesis of a differentially protected C20-C38 segment of the brasilinolides is described. Iterative 1,4-syn aldol additions and ketone reductions were employed to construct the two related stereotetrads, while a sequence of Horner-Wadsworth-Emmons (HWE) coupling, CBS reduction, and Sharpless AE installed the epoxy alcohol functionality.",10.1021/ol802769e,2009-01-05,0.6234825987130999
Organic Letters,Enantioselective Total Synthesis of (+)-Amphirionin-4,An enantioselective total synthesis of (+)-amphirionin-4 has been accomplished in a convergent manner. The synthesis features an efficient enzymatic lipase resolution to access the tetrahydrofuranol core in optically active form. The functionalized tetrahydrofuran derivative was synthesized via an oxocarbenium ion-mediated highly diastereoselective syn-allylation reaction. The polyene side chain was synthesized using Stille coupling reactions. Nozaki-Hiyama-Kishi coupling was utilized to construct the C-8 stereocenter and complete the synthesis of (+)-amphirionin-4.,10.1021/acs.orglett.6b00942,2016-04-26,0.6234662089821073
Journal of Organic Chemistry,Total Synthesis and Preliminary Biological Evaluation of <i>cis</i>-Solamin Isomers,"An efficient total synthesis of cis-solamin (1) has been achieved in 21% overall yield and with a longest linear sequence of just 11 steps from aldehyde 8. A key feature of the approach was the use of asymmetric permanganate-promoted oxidative cyclization to introduce four of the five required stereocenters in a single step. The use of robust and chemoselective methodology meant that the use of protecting groups could be avoided during the assembly of cis-solamin (1) from the three fragments 23, 6, and 4. The methodology was also applied to the synthesis of three further cis-solamin isomers 2, ent-1, and ent-2. Cytotoxicity and hemolytic properties of cis-solamin isomers and synthetic intermediates are reported.",10.1021/jo049909g,2004-04-13,0.6234661393773256
Journal of Organic Chemistry,Total Synthesis of the Marine Alkaloid Halichlorine: Development and Use of a General Route to Chiral Piperidines,"The total synthesis of the marine alkaloid halichlorine is described, based on an approach that involves constructing the fully substituted asymmetric center at an early stage. The five-membered ring is formed by 5-exo-trig radical cyclization and the unsaturated six-membered ring by a process that formally represents a sequential combination of conjugate addition and S(N)2' displacement-a method that is general for making bicyclic compounds with nitrogen at a ring fusion position. A formal synthesis of (+)-halichlorine is also reported, based on the development of a general method for preparing optically pure piperidines. The key step of this method, which was used to make one of our intermediates, is the Claisen rearrangement of a 4-vinyloxy-3,4-dihydro-2H-pyridine-1-carboxylic acid benzyl ester. Such O-vinyl compounds are easily generated in situ from the corresponding alcohols, which are themselves readily assembled from serine and terminal acetylenes.",10.1021/jo901481n,2009-09-09,0.623460009379827
Tetrahedron,"New synthetic route for selectively substituted 1,n-diamines. Synthesis of N-aryl tetra- and pentamethylenediamines",,10.1016/j.tetlet.2010.07.075,2010-07-20,0.6234525018943431
Journal of Organic Chemistry,Enantioselective Synthesis of a Mealybug Pheromone with an Irregular Monoterpenoid Skeleton,"The first enantioselective synthesis of a mealybug sex pheromone with an unprecedented monoterpenoid skeleton has been accomplished by using a highly diastereoselective conjugate addition of an organocopper reagent to a gamma-alkyl-alpha,beta-unsaturated ester intermediate as the key step.",10.1021/jo801147c,2008-08-05,0.6234456301652058
Organic Letters,"Total Syntheses of (±)-<i>cis</i>-Trikentrin A and (±)-<i>cis</i>-Trikentrin B via Electrocyclic Ring Closures of 2,3-Divinylpyrrolines","[Structure: see text] A convergent and versatile strategy for the diastereoselective syntheses of (+/-)-cis-trikentrin A and B in 10 and 12 steps, respectively, from commercially available N-BOC-2-pyrrolidinone is described. The key step in each of the total syntheses is the construction of the central benzene ring via a facile 6pi-electrocyclic ring closure of an appropriately substituted 2,3-divinylpyrroline, in turn, readily available by a Stille coupling reaction.",10.1021/ol061259a,2006-06-27,0.6234425771172943
Organic Letters,Stereoselective Total Synthesis of (±)-Alstoscholarisine E,"The shortest synthesis to date of (±)-alstoscholarisine E was accomplished in seven linear steps from commercially available reagents and 15.2% overall yield. The approach features a tandem vinylogous Mannich reaction and hetero-Diels-Alder reaction to access the core. A novel tactic to induce diastereoselective reduction of the cyclic vinyl ether was discovered, and a mild procedure to form the bridged aminal ring by partial reduction of the lactam ring via iridium-catalyzed hydrosilylation was developed.",10.1021/acs.orglett.9b04093,2019-12-02,0.6234397452717221
Organic Letters,Stereocontrolled Total Synthesis of (−)-Callipeltoside A,"[structure: see text] A highly stereocontrolled total synthesis of the cytotoxic macrolide (-)-callipeltoside A has been achieved in 23 steps (4.8% overall). Notable features include a novel asymmetric vinylogous aldol reaction to install the C13 stereocenter and (E)-trisubstituted alkene, an anti-selective aldol addition, a Sonogashira coupling, and, last, a Schmidt-type glycosylation to attach the sugar unit.",10.1021/ol0357853,2003-10-11,0.6234346083884209
Tetrahedron,Efficient stepwise and one pot three-component synthesis of 2-amino-4-(2-oxo-2H-chromen-3-yl)thiophene-3-carbonitriles,,10.1016/j.tetlet.2014.10.021,2014-10-13,0.6234038581114095
Tetrahedron,Studies on the total synthesis of lactacystin. An improved aldol coupling reaction and a β-lactone intermediate in thiol ester formation,,10.1016/s0040-4039(00)61575-7,1993-10-01,0.6233994380474996
Organic Process Research & Development,Conversion of the Laboratory Synthetic Route of the <i>N</i>-Aryl-2-benzothiazolamine R116010 to a Manufacturing Method,"A facile and large-scale preparation of the antitumor agent R116010 has been developed. The new synthetic process requires four steps: (i) Friedel−Crafts reaction of N -phenyl-2-benzothiazolamine with 2-chloropropionyl chloride, (ii) conversion of the α-chloroketone into the corresponding α-(dimethylamino)ketone and resolution of the latter, (iii) reduction of the chiral aminoketone with resultant formation of the β-amino alcohol and finally (iv) conversion of the amino alcohol into the β-aminoimidazole R116010. The key strategic improvement is the crystallization-induced diastereomeric dynamic resolution of the aminoketone, leading to the chiral ketone in 90% yield and 90% enantiomeric purity. This new process improves the overall yield from 0.26 to 18.8% without tedious chromatographic separations and hazardous reaction conditions.",10.1021/op0100201,2001-07-25,0.623391929547147
Synthesis,An Efficient Synthesis of Thalifoline,An efficient multi-step approach for the synthesis of the isoquinolin-1-one alkaloid thalifoline (1) is described. The key intermediate carbamate 8a underwent a modified Bischler-Napieralski-type cyclization using Banwell’s Tf2O/DMAP conditions to form the lactam 9a under mild conditions and in excellent yield.,10.1055/s-2002-34844,2002-01-01,0.6233904399505971
Tetrahedron,Synthesis of [13]-membered macrocyclic stevastelins via a transesterification reaction as the key step: total synthesis of stevastelin C3,,10.1016/j.tetlet.2005.09.037,2005-09-27,0.6233767669711794
European Journal of Organic Chemistry,Organocatalytic Mannich Reactions on a Carbapenem Core – Synthesis of Mannich Bases and Bicyclic Diazanonanes,Abstract An efficient diastereoselective synthesis of carbapenem Mannich bases was developed using organocatalysis. This method also provides a route to new highly functionalized diazabicyclo[4.2.1]nonanes of proposed biological significance.,10.1002/ejoc.201301823,2014-02-06,0.623369716355877
Journal of Organic Chemistry,Total Synthesis of Acinetoferrin,"The total synthesis of a novel siderophore, acinetoferrin, is described. The key transformation involves the tandem oxidation and acylation of the N 3 -amino group of N 1 -BOC propane diamine prior to coupling with the external carboxyls of citric acid. A “one-pot−two-step” reaction converted a primary amine (RNH 2 ) into a O -benzoyl hydroxamate (i.e., RN(OOCPh)COR ‘ ) in good yield (68%). These studies demonstrated the utility of the O -benzoyl protecting group in the synthesis of α,β-unsaturated hydroxamic acids.",10.1021/jo9717144,1998-02-04,0.6233489360555284
Organic Process Research & Development,Process Development for the Sulfonamide Herbicide Pyroxsulam,"The development of a manufacturing process for the initial commercial production of pyroxsulam sulfonamide herbicide is described. The process encompasses seven reaction steps, and includes a new route to 4-(trifluoromethyl)pyridines, a scaleable method of lithiating a pyridine intermediate, and a sulfilimine-catalyzed formation of a sulfonamide.",10.1021/op700281w,2008-03-01,0.6233479514757244
Angewandte Chemie International Edition,Graphical Abstract: Angew. Chem. Int. Ed. 7/2021,describe anovel route for the synthesis of carbon materials with ultrahigh N-doping,10.1002/anie.202180711,2021-02-08,0.6233432731571437
Tetrahedron,Total synthesis of 4(RS)-F4t-isoprostane methyl ester,,10.1016/s0040-4039(00)00508-6,2000-05-01,0.6233390618842917
Tetrahedron,The regiospecific total synthesis of lavendamycin methyl ester,,10.1016/s0040-4039(01)80063-0,1984-01-01,0.6233390618842917
Journal of the American Chemical Society,Evolution of a Synthetic Strategy:  Total Synthesis of (±)-Welwitindolinone A Isonitrile,An efficient and highly stereoselective total synthesis of the natural product (+/-)-welwitindolinone A isonitrile (1) is described. The bicyclo[4.2.0]octane core of 1 was established by a regio- and diastereoselective [2+2] ketene cycloaddition. The C12 quaternary center and vicinal stereogenic chlorine were installed in a single operation with excellent stereocontrol via a chloronium ion mediated semipinacol rearrangement. Described strategies for construction of the spiro-oxinole include a SmI2-LiCl mediated reductive cyclization and a novel anionic cyclization that simultaneously constructs the spiro-oxindole and vinyl isonitrile moieties.,10.1021/ja076663z,2008-01-17,0.6233362276749581
Organic Letters,Asymmetric Total Synthesis of Dragonbloodins A1 and A2,"The first asymmetric total synthesis of dragonbloodins A1 and A2, a pair of unprecedented chalcone-flavan heterotrimmers, has been achieved through a series of rationally designed or bioinspired transformations. Key elements of the synthesis include a highly efficient heterotrimerization reaction to assemble the two chalcone units and one flavan unit in one pot and a tandem oxidative dearomatization/cyclization/oxygenation reaction to forge the polycyclic core of dragonbloodins A1 and A2. The present synthesis unambiguously confirms the biogenetic relationship and absolute stereochemistry of dragonbloodins A1 and A2.",10.1021/acs.orglett.8b00315,2018-03-12,0.6233304568529854
Tetrahedron,"Synthesis of 6-amino-2,3-dihydropyridine-4-thiones via novel efficient thioenolate-carbodiimide rearrangement",,10.1016/j.tetlet.2016.08.010,2016-08-06,0.6233263970842079
Journal of the American Chemical Society,Total Synthesis of Apoptolidin:  Completion of the Synthesis and Analogue Synthesis and Evaluation,"The total synthesis of apoptolidin (1) is reported together with the design, synthesis, and biological evaluation of a number of analogues. The assembly of key fragments 6 and 7 to vinyl iodide 3 via dithiane coupling technology was supplemented by a second generation route to this advanced intermediate involving a Horner-Wadsworth-Emmons coupling of fragments 22 and 25. The final stages of the synthesis featured a Stille coupling between vinyl iodide 3 and vinylstannane 2, a Yamaguchi lactonization, a number of glycosidations, and final deprotection. The developed synthetic technology was applied to the construction of several analogues including 74, 75, and 77 which exhibit significant bioactivity against tumor cells.",10.1021/ja030496v,2003-11-21,0.6233244058682074
Organic Process Research & Development,An Improved Process for the Preparation of Tenofovir Disoproxil Fumarate,"The current three-step manufacturing route for the preparation of tenofovir disoproxil fumarate ( 1 ) was assessed and optimized leading to a higher yielding, simpler, and greener process. Key improvements in the process route include the refinement of the second stage through the replacement of the problematic magnesium tert -butoxide (MTB) with a 1:1 ratio of a Grignard reagent and tert -butanol. The development of a virtually solvent-free approach and the establishment of a workup and purification protocol which allows the isolation of a pure diethyl phosphonate ester ( 8 ) was achieved.",10.1021/acs.oprd.5b00364,2016-03-04,0.623322370757932
Chemical Science,Development of a route to chiral epidithiodioxopiperazine moieties and application to the asymmetric synthesis of (+)-hyalodendrin,Development of a novel methodology that takes advantage of the bridgehead carbanion and the traceless transfer of the stereochemistry of <sc>l</sc> -cysteine allowed the first asymmetric synthesis of hyalodendrin.,10.1039/c3sc53222d,2014-01-01,0.6233186097891952
Synlett,A Concise Synthesis of (-)-Codonopsinine and an Approach to Synthesis of (+)-Hyacinthacines A<sub>1</sub>and A<sub>2</sub>from a Polyhydroxylated Cyclic Nitrone,"Synthesis of (-)-codonopsinine (2) was accomplished in seven steps that involved an addition of five-membered cyclic nitrone 1, readily obtained from l-xylose, with the Grignard reagent. Nitrone 1 also underwent intermolecular cycloaddition with several α,β-unsaturated esters 12 to afford cycloadducts 13, one of which, 13c, was elaborated to the key intermediate 17 for (+)-hyacintha­cines A1 (3a) and A2 (3b).",10.1055/s-2003-36236,2002-01-01,0.6233175431444077
Organic Process Research & Development,Practical Synthesis of Roscovitine and CR8,"Roscovitine and CR8 are potent inhibitors of cyclin-dependent kinases. A scalable synthesis of both inhibitors is described. In the case of CR8, the biarylmethylamine moiety was obtained as a stable and high-purity salt.",10.1021/op800284k,2009-02-26,0.6233173174032337
Organic Process Research & Development,"A Practical Synthesis of the TGFβRI Inhibitor <i>N</i>-(4-(3-(6-(Difluoromethyl)pyridin-2-yl)-1<i>H</i>-pyrrolo[3,2-<i>b</i>]pyridin-2-yl)pyridin-2-yl)acetamide via One-Pot Sequential Sonogashira and Cacchi Reactions Catalyzed by Pd(OAc)<sub>2</sub>/BINAP","N -(4-(3-(6-(Difluoromethyl)pyridin-2-yl)-1 H -pyrrolo[3,2- b ]pyridin-2-yl)pyridin-2-yl)acetamide ( 5 ) is a potent inhibitor of TGFβRI kinase that provides durable antitumor activity when combined with an anti-PD-1 antibody. In order to conduct a full range of preclinical studies, over 150 g of high-quality material was required. The original discovery route through a stepwise copper-mediated Sonogashira reaction, trifluoroacetamide formation, and Cacchi reaction suffered from scale-up issues, mainly associated with tedious chromatographic purification of intermediates. This communication describes a chromatography-free one-pot synthesis of 5 via sequential Sonogashira and Cacchi reactions promoted by the superior catalyst Pd(OAc) 2 /BINAP, which was discovered by catalyst screening.",10.1021/acs.oprd.0c00015,2020-02-24,0.6233170578512518
Synlett,A Practical and Highly Efficient Procedure for the Synthesis of the Trifluoromethylpyrazol-Derived Canonical Transient Receptor Potential Channel (TRPC3) Inhibitor Pyr3 and Its Derivatives,"Abstract Canonical transient receptor potential (TRPC) channels play a variety of diverse biological functions. Among the subgroups of the TRPC family (TRPC3, TRPC6, and TRPC7), TRPC3 has been implicated in several diseases, including neurological and cardiovascular diseases, cancer, and neurodegeneration. A pyrazole-based compound Pyr3 is a selective TRPC3 channel inhibitor which is now a standard tool compound to study conditions associated with TRPC3 dysregulation. However, the reported literature syntheses of Pyr3 either provided low yield or involved microwave reactions and harsh reaction conditions. We have developed a practical and highly efficient procedure for the synthesis of Pyr3 and its derivatives in high yields which is suitable for scale-up synthesis.",10.1055/s-0043-1773516,2025-01-29,0.6233152386722681
Organic Process Research & Development,The Development of a Manufacturing Route for the GPIIb/IIIa Receptor Antagonist SB-214857-A. Part 2:  Conversion of the Key Intermediate SB-235349 to SB-214857-A,"The process development to the manufacturing route to (2 S )-7-([4,4‘-bipiperidin]-1-ylcarbonyl)-2,3,4,5-tetrahydro-4-methyl-3-oxo-1 H -1,4-benzodiazepine-2-acetic acid hydrochloride (SB-214857-A, lotrafiban) is described. The starting point is the previously reported intermediate (2 RS )-2,3,4,5-tetrahydro-4-methyl-3-oxo-1 H -1,4-benzodiazepine-2-acetic acid methyl ester. The first stage is a lipase-catalysed resolution of the racemic ester to (2 S )-2,3,4,5-tetrahydro-4-methyl-3-oxo-1 H -1,4-benzodiazepine-2-acetic acid and subsequent iodination using a pyridine iodine monochloride complex to give (2 S )-2,3,4,5-tetrahydro-7-iodo-4-methyl-3-oxo-1 H -1,4-benzodiazepine-2-acetic acid. The unreacted ( R )-enantiomer of the starting ester is recovered and recycled to the racemate by treatment with sodium methoxide. The next stage describes the palladium-catalysed aminocarbonylation of the aryl iodide with 4,4‘-pyridylpiperidine to give (2 S )-2,3,4,5-tetrahydro-4-methyl-3-oxo-7-[[4-(4-pyridinyl)-1-piperidinyl]carbonyl]-1 H -1,4-benzodiazepine-2-acetic acid dihydrate. The third stage is the hydrogenation of the pyridine subunit over palladium on charcoal to obtain the zwitterionic (2 S )-7-([4,4‘-bipiperidin]-1-ylcarbonyl)-2,3,4,5-tetrahydro-4-methyl-3-oxo-1 H -1,4-benzodiazepine-2-acetic acid hexahydrate. The final stage is the formation of the hydrochloride salt to afford the drug substance.",10.1021/op034023k,2003-07-26,0.6232871643096574
Journal of Organic Chemistry,"Enantioselective Synthesis of DIANANE, a Novel <i>C</i><sub>2</sub>-Symmetric Chiral Diamine for Asymmetric Catalysis","DIANANE (endo,endo-2,5-diaminonorbornane) is a novel chiral C(2)-symmetric diamine, based on the rigid bicyclo[2.2.1]heptane scaffold. Schiff-base ligands derived from DIANANE have already found use in asymmetric catalysis, e.g., in the highly enantioselective Nozaki-Hiyama-Kishi reaction. We herein describe a practical synthesis of enantiomerically pure DIANANE, starting from norbornadiene in four steps: (i) Pd-MOP catalyzed Hayashi-hydrosilylation/Tamao-Fleming oxidation, (ii) oxidation to norbornane-2,5-dione, (iii) endo-selective reductive amination with benzylamine, and (iv) hydrogenolytic debenzylation. None of the steps involves chromatographic purification. For the Tamao-Fleming oxidation, the use of hydrogen peroxide in the form of its urea clathrate instead of aqueous solution proved beneficial. By the above sequence, enantiomerically pure (ee >or=99%) DIANANE was obtained from norbornadiene in 40-50% overall yield. The relative and absolute configuration of DIANANE was confirmed by X-ray crystallography of the DIANANE bis-tosylamide, and of its bis-camphorsulfonamide. Furthermore, the synthesis and X-ray crystal structure of the Schiff-base ligand derived from DIANANE and 3,5-di-tert-butyl salicylic aldehyde are reported.",10.1021/jo035841d,2004-04-01,0.6232871501670829
Journal of the American Chemical Society,Total Synthesis of Ritterazine B,"The first total synthesis of the cytotoxic alkaloid ritterazine B is reported. The synthesis features a unified approach to both steroid subunits, employing a titanium-mediated propargylation reaction to achieve divergence from a common precursor. Other key steps include gold-catalyzed cycloisomerizations that install both spiroketals and late stage C-H oxidation to incorporate the C7' alcohol.",10.1021/jacs.1c01372,2021-03-09,0.6232636471644544
Tetrahedron,Combinatorial synthesis of modular chiral cyclophanes,,10.1016/0040-4039(96)01945-4,1996-11-01,0.6232541453912046
Tetrahedron,"Synthesis of chiral 1,2-diamines",,10.1016/s0040-4039(00)99552-2,1989-01-01,0.6232541453912046
Tetrahedron,Synthesis of chiral cyclopentenoids,,10.1016/s0040-4039(00)86953-1,1982-01-01,0.6232541453912046
Tetrahedron,"Stereorational synthesis of a chiral D3, triketone",,10.1016/s0040-4039(00)72624-4,1975-01-01,0.6232541453912046
Tetrahedron,Synthesis of chiral α-alkoxyketones via allene oxides,,10.1016/s0040-4039(96)02436-7,1997-02-01,0.6232541453912046
Tetrahedron,Synthesis and CD spectrum of chiral porphyrin dimer,,10.1016/0040-4039(95)01138-8,1995-08-01,0.6232541453912046
Tetrahedron,"Synthesis of chiral 2′,3′-pyranone(pyrrolidinone)-fused tryptamines",,10.1016/s0040-4039(02)02537-6,2003-01-01,0.6232541453912046
Tetrahedron,Synthesis of chiral spiroacetals from carbohydrates,,10.1016/0040-4039(95)00766-6,1995-06-01,0.6232541453912046
Tetrahedron,Stereocontrolled synthesis of chiral nonracemic halotetrahydropyrans,,10.1016/s0040-4039(00)74222-5,1992-04-01,0.6232541453912046
Tetrahedron,A formal synthesis of (−)-swainsonine from a chiral aziridine,,10.1016/j.tetlet.2010.04.069,2010-04-22,0.6232541453912046
Tetrahedron,Sirodesmin A: Synthesis of a chiral left half.,,10.1016/s0040-4039(00)87093-8,1982-01-01,0.6232541453912046
Tetrahedron,"Expeditious synthesis of chiral 1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazines",,10.1016/j.tetlet.2013.02.067,2013-02-27,0.6232541453912046
Tetrahedron,"Synthesis of a protonated C2-symmetric N,N-chiral “proton sponge”",,10.1016/s0040-4039(98)00930-7,1998-06-01,0.6232541453912046
Tetrahedron,"The synthesis of chiral annulet 1,4,7-triazacyclononanes",,10.1016/s0040-4039(02)00705-0,2002-05-01,0.6232541453912046
Tetrahedron,Synthesis of chiral malathion and isomalathion,,10.1016/s0040-4039(00)91635-6,1992-03-01,0.6232541453912046
Tetrahedron,Synthesis of Chiral Phosphetanes,,10.1016/s0040-4039(97)00508-x,1997-04-01,0.6232541453912046
Tetrahedron,Chiral synthesis of statine,,10.1016/s0040-4039(00)98595-2,1985-01-01,0.6232541453912046
Tetrahedron,Synthesis and CD Spectrum of Chiral Porphyrin Dimer,,10.1016/00404-0399(50)11388-,1995-08-14,0.6232541453912046
Journal of the American Chemical Society,Asymmetric Total Synthesis of Trilobacin via Organoselenium-Mediated Oxonium Ion Formation/SiO<sub>2</sub>-Promoted Fragmentation,"An asymmetric total synthesis of trilobacin (1), an annonaceous acetogenin with potent anticancer activities, was accomplished wherein the construction of its erythro-bis(2,2')-tetrahydrofuran core 2 featured a novel organoselenium-mediated oxonium ion formation/SiO(2)-promoted fragmentation of alpha,alpha'-cis-oxocene 3.",10.1021/ja106116v,2010-08-11,0.6232508499310566
Tetrahedron,"Synthesis and field bioassay of the Israeli pine bast scale, Matsucoccus josephi, female sex pheromone",,10.1016/s0040-4039(00)73904-9,1993-08-01,0.6232451107125454
Tetrahedron,A cobaloxime-mediated synthesis of the ras farnesyl-protein transferase inhibitor chaetomellic acid A,,10.1016/s0040-4039(00)73114-5,1994-06-01,0.6232409022533553
Tetrahedron,New synthetic route to (S)-(−)-equol through allylic substitution,,10.1016/j.tetlet.2008.06.085,2008-06-23,0.6232404474709673
Organic Letters,Stereocontrolled Total Synthesis of (±)-Catharanthine via Radical-Mediated Indole Formation,"A stereocontrolled total synthesis of (±)-catharanthine, 1, has been completed. The key step involves the radical-mediated cyclization of a highly functionalized intermediate to furnish the corresponding indole. The cyclization utilizes a simple phosphorus-based radical-reducing agent. This synthesis provides a potential route for the production of analogues of catharanthine and is more convergent and experimentally less complex than previous syntheses of 1 .",10.1021/ol990749i,1999-09-08,0.6232397373035776
Journal of Organic Chemistry,Stereoselective Synthesis of (+)-Boronolide,"The delta-lactone boronolide (+)-1, a pharmacologically active, naturally occurring product, has been synthesized in enantiopure form with L-erythrulose as the chiral starting material. The key steps of the synthesis were a highly stereoselective aldol-reduction one-pot sequence, an indium-mediated diastereoselective aldehyde allylation, and a ring-closing metathesis.",10.1021/jo025813f,2002-08-13,0.6232317325154252
Journal of Organic Chemistry,A Gold-Catalyzed Domino Process to the Steroid Framework,"The facile formation of the B and C ring of rac-desoxyequilenin and of a chrysenone derivative in just one preparative step is demonstrated, applying a gold-catalyzed domino process, which involves a benzopyrylium cation as the key intermediate and an intramolecular [3 + 2] cycloaddition as the key step.",10.1021/jo060606r,2006-08-09,0.6232257022402848
Synlett,Synthesis of Azido Analogues of Medermycin,"The synthesis of azido analogues 2a,2b of the pyrano-naphthoquinone antibiotic medermycin I has been achieved in eight steps from naphthol 8 and azido glycosyl sugar 7 in 9.3% overall yield. Key steps include the direct (BF3Et2O)-Et-. promoted C-glyc",10.1055/s-2002-32955,2002-01-01,0.6232224460028655
Journal of Organic Chemistry,A New Stereoselective Synthesis of Ciguatoxin Right Wing Fragments,"The right wings (13 and 14) of ciguatoxins were synthesized highly stereoselectively. Key transformations in the synthesis are (i) an oxiranyl anion strategy to attach the H ring, (ii) intramolecular carbonyl olefination to cyclize the J ring, (iii) regio- and stereoselective reduction of the epoxyacetal to install the C42-stereocenter, and (iv) stereoselective reductive etherification to construct the K ring. The present procedure greatly improved the stereoselectivity and efficiency in comparison to a previous synthesis. Remarkably, only 23 steps were required from monocyclic I ring 5 to construct the ciguatoxin right wings. The high practicality of the present synthesis ensures a sufficient supply of these complex fragments for total syntheses and biomedical applications.",10.1021/jo049877x,2004-03-17,0.6232003877811993
Tetrahedron,FeCl3 mediated one-pot route to nitriles,,10.1016/j.tetlet.2013.06.134,2013-07-05,0.6231989007943844
Journal of the American Chemical Society,Toward More “Ideal” Polyketide Natural Product Synthesis: A Step-Economical Synthesis of Zincophorin Methyl Ester,"A highly efficient and step-economical synthesis of zincophorin methyl ester has been achieved. The unprecedented step economy of this zincophorin synthesis is principally due to an application of the tandem silylformylation-crotylsilylation/Tamao oxidation-diastereoselective tautomerization reaction, which achieves in a single step what would typically require a significant multistep sequence.",10.1021/ja201467z,2011-04-27,0.6231935079713381
Synthesis,"Design, Synthesis and Olfactory Properties of 2-Substituted 2-<i>tert</i>-Butyl-5-methyl-2,5-dihydrofurans: <i>seco</i>-Derivatives of Theaspiranes","Two seco-theaspiranes with pronounced blackcurrant notes, 2-tert-butyl-5-methyl-2-propyl-2,5-dihydrofuran (7) and 2-tert-butyl-5-methyl-2-propyltetrahydrofuran (8), were synthesized by a synthetic sequence consisting of Grignard reaction, Lindlar ­hydrogenation, and cyclization followed by optional Pd-catalyzed hydrogenation. The sequence was modified for the synthesis of the oxygenated analogs 2-(2′-tert-butyl-5′-methyltetrahydrofuran-2′-yl)propan-2-ol (9) and 3-(2′-tert-butyl-5′-methyltetrahydrofuran-2′-yl)butan-2-one (10). The first modification featured trimethyl­silyl ether protection and stepwise construction of the alkyne moiety necessitated by steric hindrance. In the second modification, a but-2-en-2-yl group was utilized as latent 3-hydroxybut-1-en-2-yl functionality, and the steric constraint around the tertiary hydroxy group was exploited to introduce a stereocenter by SN2 ring closure. As for the parent compounds 7 and 9, the odor of the oxygenated seco-­theaspiranes was shifted towards a woody tonality. The like-diastereo­mer 9a even had a typical patchouli profile, and the ­enantiomers 10a and 10b differed significantly in their olfactory properties.",10.1055/s-2005-918404,2005-09-23,0.6231895382172982
Journal of Organic Chemistry,Synthesis of the BCDE Molecular Fragment of Azadiradione Mediated by Titanocene(III),"A practical, short, and diastereoselective synthesis of the azadiradione BCDE fragment from a readily available starting material is described. The key step was the titanocene(III)-promoted tandem cyclization of unsaturated epoxy nitrile.",10.1021/jo401646g,2013-09-14,0.6231883749776763
Angewandte Chemie International Edition,A Practical Synthesis of (−)‐Oseltamivir,"Keep it simple: Still in hot demand, the influenza drug (−)-oseltamivir phosphate (tamiflu; see scheme) has now been synthesized from pyridine by using inexpensive reagents. A strict minimum of purification steps are required in a synthetic route which features an asymmetric Diels–Alder reaction, a bromolactonization, a Hofmann rearrangement, and a domino transformation of a bicyclo[2.2.2] system into an aziridine intermediate.",10.1002/anie.200701754,2007-06-26,0.6231790946799817
Journal of Organic Chemistry,"Total Synthesis of 19-Nordigitoxigenin, An Antiaroside Y Aglycon","The first total synthesis of 19-nordigitoxigenin, an aglycon of antiroside Y, has been achieved. The key steps of our synthesis are (i) construction of the 19-norsteroid ring system via a Mizoroki-Heck reaction between a bromoanisole corresponding to the A-ring and cyclic alkene incorporating the CD-rings, followed by a Friedel-Crafts-type cyclodehydration, and (ii) incorporation of the butenolide moiety at C17 via a silyl-tethered radical cyclization and subsequent ozone oxidation.",10.1021/acs.joc.3c01629,2023-10-12,0.6231684854670166
Tetrahedron,A hydroformylation route to β-substituted pyrroles,,10.1016/s0040-4039(00)74496-0,1991-02-01,0.6231650431019485
Tetrahedron,A stereocontrolled route to 2-substituted chromans,,10.1016/s0040-4039(00)01530-6,2000-10-01,0.6231650431019485
Tetrahedron,Solvomercuration-demercuration of limonene with Hg(BF4)2; A chemo-and regiospecific route to 8-substituted p-menthenes,,10.1016/s0040-4039(00)61218-2,1992-08-01,0.6231650431019485
Tetrahedron,"The π-route to 2,4-substituted adamantanes",,10.1016/s0040-4039(01)98130-4,1970-01-01,0.6231650431019485
Tetrahedron,The π-route to 2-substituted adamantanes,,10.1016/s0040-4039(01)98681-2,1970-01-01,0.6231650431019485
Synlett,Aromatics to Diquinanes: AnExpeditious Synthesis of Tetramethylbicyclo[3.3.0]octaneFramework of Ptychanolide,"An expeditious route to methyl-7-oxo-1,4,5,8-tetramethylbicyelo[3.3.0]octane-3-carboxylate from a simple aromatic precursor is described. Oxidative dearomatization of 2-hydroxymethyl-3,4,6-trimethylphenol into spiroepoxycycloliexa-2,4-dierone, its cycloaddition and triplet-sensitized 1,2-acyl shift, and stereochemical inversion are the key features Of Our methodology.",10.1055/s-0028-1087275,2008-11-26,0.6231531552670678
Journal of Organic Chemistry,An Enantioselective Formal Synthesis of Montelukast Sodium,"A formal synthesis of the antiasthma drug montelukast sodium is described, wherein the key chiral diol intermediate was accessed with greater convergence of the C-C bond-forming steps as compared to previous routes. Improved synthetic efficiency was achieved by deploying homogeneous metal-based catalysis in two pivotal steps. In the first, a tandem Mizoroki-Heck reaction and double-bond isomerization between a previously known allyl alcohol intermediate and a hindered 2-(2-halophenyl)propan-2-ol secured direct access to the 3-(2-(2-hydroxypropan-2-yl)phenyl)-1-phenylpropan-1-one moiety in the product. In the second step, asymmetric hydrogenation of the ketone functionality in the Mizoroki-Heck reaction product provided a convenient method to introduce the benzylic alcohol chiral center and obtain the desired chiral diol precursor of montelukast sodium. A detailed catalyst screening led to the identification of ((R)-Xyl-BINAP)((R,R)-DPEN)RuCl2 as a catalyst that afforded an enantioselectivity of 99% ee in the hydrogenation step on a multigram lab scale at a molar substrate:catalyst loading of 5000:1.",10.1021/acs.joc.5b00197,2015-03-25,0.6231498600829157
Journal of Organic Chemistry,Studies on the Total Synthesis of Disorazole C<sub>1</sub>. An Advanced Macrocycle Intermediate,"Synthesis of protected tetradehydro-(6,6'-S)-(14,14'-S)-(16,16'-R)-disorazole (3), a potential precursor to the natural product disorazole C1 (1), is described. Key features of this work include (a) an unprecedented sequential 1,5 O --> O silyl rearrangement/Horner-Wadsworth-Emmons reaction used to construct 18, (b) a highly convergent Sonogashira reaction between the dienyl iodide 7 and the alkyne 8 to assemble the dienyne monomeric fragment 5, and (c) the selective cyclization of 5 to give either the cyclic monomer 23 or the dimer 3.",10.1021/jo010249e,2001-08-08,0.6231492800253579
Organic Process Research & Development,Efficient Access to Methyl-1-hydroxy-2-naphthoates and Heterocyclic Analogues,"We report the synthesis of methyl-1-hydroxy-2-naphthoate derivatives and heterocyclic analogues using a two-step approach. This short route employs a Heck coupling of a 2-halo-benzoate with methyl 3-butenoate followed by a Dieckmann cyclization, yielding the 1-hydroxynaphthalene-2-carboxylic acid derivatives in the multigram scale.",10.1021/acs.oprd.5b00280,2015-10-13,0.6231484752446029
Synthesis,First Synthesis of the Naturally Occurring Diazocarbonyl Compound Cremeomycin,"The first synthesis of cremeomycin (3-diazo-4-methoxy-2-oxocyclohexa-4,6-dienecarboxylic acid), a naturally occurring diazocarbonyl compound, is described. Starting from methyl 2-hydroxy-4-methoxybenzoate, nitration, hydrolysis, and reduction gave 3-amino-2-hydroxy-4-methoxybenzoic acid as the key aminophenol precursor, diazotization of which gave the diazoquinone natural product.",10.1055/s-0028-1083204,2008-10-23,0.6231367511871262
Angewandte Chemie International Edition,"Short, Enantioselective Total Synthesis of Stephacidin A","A concise route to the heptacyclic indole alkaloid stephacidin A (1) includes a simple method for the gram-scale synthesis of substituted tryptophans, a remarkable indole annulation, and the first enolate coupling of an amide to an ester. This synthesis secures the relative configuration of the natural product and paves a potential path to several of its congeners.",10.1002/anie.200461864,2004-12-07,0.6231296546910218
Organic Letters,Total Synthesis of Sinensilactam A,The total synthesis of naturally occurring (±)-sinensilactam A was achieved in 18 steps. The key steps of this work are a rhodium-catalyzed [3 + 2] cycloaddition for construction of the two all-carbon vicinal quaternary centers and a convergent and tandem condensation of the in situ generated N-acyliminium intermediate with aldehyde 20. This enabled implementation of a unified strategy for stereoselective formation of the tetracyclic hemiaminal core of sinensilactam A in a later stage. The total syntheses of applanatumol F and C8- epi-applanatumol D are also achieved using this strategy.,10.1021/acs.orglett.8b00380,2018-03-19,0.6231122482080975
European Journal of Organic Chemistry,Asymmetric Total Synthesis of (–)‐Azaspirene by Utilizing Ti‐Claisen Condensation and Ti‐Direct Aldol Reaction,"A successful asymmetric total synthesis of (–)‐azaspirene has been accomplished by utilizing (3 R )‐6‐cinnamyl‐3‐methyl‐3‐phenyl‐1,4‐dioxane‐2,5‐dione, a readily accessible chiral template. The present method involves two distinctive TiCl 4 /amine‐mediated reactions: (i) an asymmetric Ti‐crossed‐Claisen condensation of the chiral template with propanoyl chloride followed by methanolysis to afford methyl (2 R )‐(4 E )‐2‐hydroxy‐5‐phenyl‐2‐propanoylpent‐4‐enoate, the key chiral synthon and (ii) a robust Ti‐direct aldol addition reaction, instead of the reported lithium diisopropylamide/hexamethylphosphorictriamide (LDA/HMPA) or potassium hexamethyldisilazide (KHMDS)‐mediated reaction, by using the trimethylsilyl (TMS) ether of α‐acyl‐γ‐lactam to successfully furnish the new aldol adduct. Final oxidation, cyclization, and tert ‐butyldimethylsilyl (TBS) removal produced (–)‐azaspirene from the key template in 23 steps (total yield 1.7 %).",10.1002/ejoc.201600766,2016-08-26,0.6230976418001767
Journal of Organic Chemistry,"Total Synthesis of Robustaflavone, a Potential Anti-Hepatitis B Agent","Robustaflavone, a naturally occurring compound, is an inhibitor of hepatitis B virus replication in vitro. Robustaflavone is a biflavanoid composed of two units of apigenin (5,7,4‘-trihydroxyflavone) joined via a biaryl linkage between the 6-position of one unit and the 3‘-position of the other (I6,II3‘-biapigenin). The natural material was isolated from the seed-kernels of Rhus succedanea . To provide ready access to sufficient quantities of material for continued biological studies, as well as to provide a general route for the preparation of structural analogues, a total synthesis of robustaflavone was pursued. The total synthesis was approached by constructing apigenin ethers containing functionalities at the 6- and 3‘-positions which could be cross-coupled using transition metal catalysis. Key steps of the synthesis included development of a regioselective iodination of an apigenin derivative at the 6-position. Also key was the formation of an apigenin 3‘-boronate using a palladium-catalyzed exchange of the corresponding 3‘-iodide with a diboron reagent. Finally, identification of appropriate reaction conditions for Suzuki coupling to form the sterically congested 6−3‘‘‘ biaryl bond of robustaflavone provided access to the desired biflavanoid system. This work represents the first total synthesis of robustaflavone.",10.1021/jo981186b,1998-11-14,0.6230956613462573
Journal of Organic Chemistry,Cyclobutane Synthesis and Fragmentation. A Cascade Route to the <i>Lycopodium</i> Alkaloid (−)-Huperzine A,"An asymmetric total synthesis of the nootropic alkaloid (-)-huperzine A was completed using a cascade sequence initiated by an intramolecular aza-Prins reaction and terminated by a stereoelectronically guided fragmentation of a cyclobutylcarbinyl cation as the key step in assembling the bicyclo[3.3.1]nonene core of the natural product. Intramolecular [2 + 2]-photocycloaddition of the crotyl ether of (S)-4-hydroxycyclohex-2-enone afforded a bicyclo[4.2.0]octanone containing an embedded tetrahydrofuran in which the cyclohexanone moiety was converted to a triisopropylsilyl enol ether and functionalized as an allylic azide. The derived primary amine was acylated with α-phenylselenylacrylic acid, and the resulting amide was reacted with trimethylaluminum to give a [2 + 2]-cycloadduct, which underwent retroaldol fission to produce a fused α-phenylselenyl δ-lactam. Periodate oxidation of this lactam led directly to an α-pyridone, which was converted to a fused 2-methoxypyridine. Reductive cleavage of the activated ""pyridylic"" C-O bond in this tetracycle and elaboration of the resultant hydroxy ketone to a diketone was followed by chemoselective conversion of the methyl ketone in this structure to an endo isopropenyl group. Condensation of the remaining ketone with methyl carbamate in the presence of acid initiated the programmed cascade sequence and furnished a known synthetic precursor to huperzine A. Subsequent demethylation of the carbamate and the methoxypyridine, accompanied by in situ decarboxylation of the intermediate carbamic acid, gave (-)-huperzine A.",10.1021/acs.joc.5b01619,2015-09-10,0.623094794941315
Synlett,Total Synthesis of (±)-Membranolide,"All articles of this category The first total synthesis of racemic membranolide [methyl α-methyl-6-(1,3,3-trimethylcyclohexyl)-1(3 H )-isobenzofuranone-7-acetate] is described starting from o -methoxyphenylmagnesium bromide and 3,5,5-trimethyl-2-cyclohexen-1-one.",10.1055/s-1990-21215,1990-01-01,0.6230843478096878
Journal of Organic Chemistry,Synthesis of Tricyclic Indole-2-caboxylic Acids as Potent NMDA-Glycine Antagonists,"The practical synthesis of a series of tricyclic indole-2-carboxylic acids, 7-chloro-3-arylaminocarbonylmethyl-1,3,4,5-tetrahydrobenz[cd]indole-2-carboxylic acids, as a new class of potent NMDA-glycine antagonists is described. The synthetic route to the key intermediate 12a comprises a regioselective iodination of 4-chloro-2-nitrotoluene, modified Reissert indole synthesis, Jeffery's Heck-type reaction with allyl alcohol, Wittig-Horner-Emmons reaction, and iodination at the indole C-3 position. The key step in the route is an intramolecular cyclization of 12a to give the tricyclic indole structure. Two methods of cyclization, (1) an intramolecular radical cyclization of 12a and (2) a sequence of intramolecular Heck reaction of 12a followed by a 1,4-reduction, were performed. The resulting tricyclic indole diester 13a was selectively hydrolyzed to afford the desired tricyclic indole monocarboxylic acid 16 on a multihundred gram scale without any chromatographic purifications. Optical resolution of 16 to (-)-isomer 17 and (+)-isomer 18 was carried out, and the resulting isomers were derivatized, respectively. Evaluation of the optically active derivatives for affinity to the NMDA-glycine binding site using the radio ligand binding assay with [(3)H]-5,7-dichlorokynurenic acid revealed that the derivatives of (-)-isomer 17 were more potent than the others and that especially substituted anilide (-)-isomer 24 (K(i) = 0.8 nM) showed high affinity.",10.1021/jo010002h,2001-04-26,0.62308418364546
Angewandte Chemie International Edition,Enantioselective Total Synthesis of Terreumols A and C from the Mushroom <i>Tricholoma terreum</i>,"The cytotoxic meroterpenoids terreumol A and C from the grey knight mushroom Tricholoma terreum were synthesized for the first time. The key step of the enantioselective total synthesis of terreumol C is a ring-closing metathesis to form a trisubstituted Z double bond embedded in the 10-membered ring of the [8.4.0] bicycle. Interestingly, the presence of a free hydroxy group in the metathesis precursor prevents cyclization and favors cross metathesis. (-)-Terreumol C was converted into (-)-terreumol A by diastereoselective epoxidation. Starting from 2-bromo-3,5-dimethoxybenzaldehyde, 14 steps with an overall yield of 23 % are needed for the synthesis of (-)-terreumol A. X-ray analysis of the benzoquinone analogue of terreumol A provides independent proof of the absolute configuration.",10.1002/anie.201510709,2016-01-14,0.6230814290496998
Tetrahedron,Reductive amination of α-formyl lactones. A route to α-methylene lactones.,,10.1016/s0040-4039(01)95820-4,1973-01-01,0.6230784587647233
European Journal of Organic Chemistry,Diastereoselective Synthesis of a Precursor of Homocarbocyclic Nucleosides,"A convenient diastereoselective synthesis of an immediate precursor for a rapid access to a variety of homo-carbocyclic nucleosides, is described. The synthetic scheme involves a high yielding new type of Pd(0) catalyzed cyclization of a suitable hydrazine derivative together with a stereospecific OsO4 triggered dihydroxylation step.",10.1002/(sici)1099-0690(199911)1999:11<3085::aid-ejoc3085>3.3.co;2-j,1999-11-01,0.6230676924434752
European Journal of Organic Chemistry,Diastereoselective Synthesis of a Precursor of Homocarbocyclic Nucleosides,"A convenient diastereoselective synthesis of an immediate precursor for a rapid access to a variety of homo-carbocyclic nucleosides, is described. The synthetic scheme involves a high yielding new type of Pd(0) catalyzed cyclization of a suitable hydrazine derivative together with a stereospecific OsO4 triggered dihydroxylation step.",10.1002/(sici)1099-0690(199911)1999:11<3085::aid-ejoc3085>3.0.co;2-s,1999-11-01,0.6230676924434752
Organic Process Research & Development,"Enantiospecific Synthesis of (3<i>R</i>,4<i>R</i>)-1-Benzyl-4-fluoropyrrolidin-3-amine Utilizing a Burgess-Type Transformation","Manufacture of an EGFR inhibitor required the asymmetric synthesis of a key 3,4-trans-substituted pyrrolidine suitable for pilot-plant scale. The initial synthetic route utilized reagents and intermediates that posed safety concerns due to their energetic potential and then required supercritical fluid chromatography to access the desired single enantiomer. Burgess-type reagents provide tremendous utility in organic synthesis but see limited use on large scales because of their high cost and instability. Nevertheless, extensive process development led to a scale-friendly process where in situ formation of a Boc-Burgess reagent enabled access to a chiral cyclic sulfamate from inexpensive materials. ReactIR monitoring was used to study intermediate stability and enabled processing on a multikilogram scale. The sulfamate was converted to trans -3-fluoro-4-aminopyrrolidine 1 with complete stereospecificity. Intermediate crystallinity offered purity control points where byproducts and impurities were rejected, avoiding the need for chromatography.",10.1021/acs.oprd.9b00245,2019-07-16,0.6230658011360442
Organic Letters,Synthesis of the C3−C18 Fragment of Amphidinolides G and H,"A synthesis of an amphidinolides G and H C3-C18 subunits is reported. The C10-C18 segment 4 was prepared by a Negishi cross-coupling, whereas the synthesis of the C3-C9 fragment 5 employed an asymmetric cyanosilylation as the key step. The two segments were coupled by lithiation of iodide 4 and trapping of the anion with amide 5. The allylic epoxide moiety could be synthesized from the protected anti- mesylate 22.",10.1021/ol071024e,2007-07-07,0.6230610955370337
Journal of Organic Chemistry,A Convenient Multigram Synthesis of Highly Enantioenriched Methyl 3-Silylglycidates,"A multigram scale synthesis of the four stereoisomers of methyl 3-silylglycidates (epoxysilanes) with high enantiopurity is described. Key reactions include a Sharpless asymmetric epoxidation (SAE) of a trans-vinylsilane and an enzymatic resolution of a racemic cis-epoxysilane to establish the desired configurations. Few chromatographic separations (5 columns out of 13 steps) are required for purification, establishing a convenient reaction sequence for both the trans- and cis-isomers.",10.1021/jo060134g,2006-03-29,0.6230609421979391
Tetrahedron,"Enantioselective synthesis of curacin A. 2. Total synthesis of curacin A by condensation of C1–C7, C8–C17, and C18–C22 segments",,10.1016/0040-4039(96)00031-7,1996-03-01,0.6230550426077521
Synthesis,A Concise and Stereoselective Total Synthesis of Pestalotioprolide C Using Ring-Closing Metathesis,"The stereoselective total synthesis of the pestalotioprolide C is disclosed in 13 linear steps in 4% overall yield. The key steps in this approach are a ring-closing-metathesis protocol for the construction of the 14-membered macrolide with E-olefinic bond, a Keck allylation, and a Sharpless kinetic resolution for the installation of desired stereocenters at C4 and C7.",10.1055/s-0036-1589152,2017-12-20,0.623051760092385
Journal of the American Chemical Society,Total Synthesis of (−)-Nahuoic Acid C<sub>i</sub> (B<sub>ii</sub>),") (3), a novel cis-decalin polyketide, has been achieved. Key synthetic transformations include Type II Anion Relay Chemistry (ARC) to construct the polyol chain, a Ti-catalyzed asymmetric Diels-Alder reaction to generate the cis-decalin skeleton, and a late-stage large fragment union exploiting a Micalizio alkoxide-directed alkyne-alkene coupling tactic.",10.1021/jacs.7b08683,2017-09-21,0.6230404173011832
Tetrahedron,A diastereoselective synthesis of benzopyrans using a novel intramolecular Nicholas reaction in the key cyclisation step,,10.1016/s0040-4039(96)02392-1,1997-01-01,0.6230375977006372
Journal of the American Chemical Society,Toward the Development of a General Chiral Auxiliary. A Total Synthesis of (+)-Tetronolide via a Tandem Ketene-Trapping [4 + 2] Cycloaddition Strategy,"A highly convergent, enantioselective total synthesis of the aglycone of the tetrocarcins, (+)-tetronolide, is described. The synthesis highlights the use of several new methods, including camphor auxiliary-directed asymmetric alkylation and the enantioselective preparation of acyclic mixed acetals bearing chirality at the acetal center, and the highly efficient connection of the two major precursors via a ketene-trapping/intramolecular [4 + 2] cycloaddition strategy.",10.1021/ja0581346,2006-07-21,0.6230314259742271
Journal of Organic Chemistry,Synthesis of Illudinine from Dimedone and Identification of Activity as a Monoamine Oxidase Inhibitor,"The fungal metabolite illudinine is prepared in seven steps and ca. 55% overall yield from dimedone using an “open and shut” (ring-opening and ring-closing) strategy. Tandem ring-opening fragmentation and olefination of dimedone establishes alkyne and vinylarene functionality linked by a neopentylene tether. Oxidative cycloisomerization then provides the illudinine framework. The key innovation in this second-generation synthesis of illudinine is the use of the nitrile functional group, rather than an ester, as the functional precursor to the carboxylic acid of illudinine. The small, linear nitrile (C≡N) is associated with improved selectivity, π-conjugation, and reactivity at multiple points in the synthetic sequence relative to the carboxylic acid ester. Preliminary assays indicate that illudinine and several related synthetic analogues are monoamine oxidase inhibitors, which is the first reported indication of biological activity associated with this natural product. Illudinine was found to inhibit monoamine oxidase B (MAO-B) with an IC 50 of 18 ± 7.1 μM in preliminary assays.",10.1021/acs.joc.0c01301,2020-08-24,0.6230299948814824
Journal of Organic Chemistry,Stereoselective Formal Synthesis of (+)- and (−)-Cyclophellitol and (−)-Conduritol-B and Synthesis of (−)-Conduramine-B Derivative Using a Sulfinyl Moiety for C–O Bond Formation and α-Chloro Sulfide for C–C Bond Formation,"The formal total synthesis of both the enantiomers of cyclophellitol and conduritol-B and synthesis of conduramine-B derivative have been achieved from a common intermediate, obtained by regio- and stereoselective vicinal functionalization of a diene utilizing an intramolecular sulfinyl group as a nucleophile, followed by stereoselective preparation of an allylic sulfide by reaction of vinylzinc bromide with an electrophilic α-chloro sulfide, and last by ring-closing metathesis reaction as the key steps. The sulfoxide, sulfilimine, and sulfur ylid prepared from this common intermediate have been transformed into derivatives of conduritol-B, conduramine-B, and (-)-cyclophellitol, respectively. The silyl sulfide was converted via sila-Pummerer rearrangement, hydrolysis, and reduction in an one-pot operation to a hydroxymethyl group. [2,3]-Wittig-Still rearrangement was employed for the synthesis of (+)-cyclophellitol. The potential utility of sulfur intermediates as nucleophilic and electrophilic partners in total synthesis is elegantly demonstrated.",10.1021/acs.joc.6b00616,2016-04-20,0.6230220151606521
Organic Letters,Total Synthesis of a Conjugation-Ready Tetrasaccharide Repeating Unit of <i>Vibrio cholerae</i> O:3 O-antigen Polysaccharide,"Herein, we report the first total synthesis of the tetrasaccharide repeating unit of Vibrio cholerae O:3 O-antigen polysaccharide. The highly complex tetrasaccharide contains rare amino sugars such as d -bacillosamine and l -fucosamine, highly labile sugar ascarylose, and higher carbon sugar d - d -heptose. Stereoselective glycosylation of the notoriously reactive ascarylose with d - d -heptose, poor nucleophilicity of the axial C4-OH of l -fucosamine, and amide coupling are the key challenges encountered in the total synthesis, which was completed via a longest linear sequence of 23 steps in 4.2% overall yield.",10.1021/acs.orglett.3c04225,2024-01-10,0.6230187070779214
Journal of Organic Chemistry,Yamaguchi-Type Lactonization as a Key Step in the Synthesis of Marine Metabolites: (+)-Luffalactone,"A Yamaguchi-type cyclization of 5 and subsequent photochemical oxidation of the furanic ring are the key steps in the first synthesis of the marine metabolite (+)-luffalactone 4 and its epimer at C-16, 16-epi-luffalactone, 27. With this work, we have successfully established the absolute configuration of the natural product. The key intermediate 5 was obtained from the easily accessible diacetate 6a/6b.",10.1021/jo9013996,2009-09-21,0.6229937475292363
Journal of Organic Chemistry,"Total Synthesis of Antofine Using the Net [5+5]-Cycloaddition of γ,δ-Unsaturated Carbene Complexes and 2-Alkynylphenyl Ketones as a Key Step","A compound containing all of the carbons of the anticancer agent antofine was produced in a single step from the coupling of a gamma,delta-unsaturated carbene complex with a 2-alkynylphenyl ketone derivative. Subsequent conversion to antofine was effected in three steps.",10.1021/jo061053n,2006-07-25,0.6229814757195352
Journal of the American Chemical Society,"Total Synthesis of the CP-Molecules (CP-263,114 and CP-225,917, Phomoidrides B and A). 1. Racemic and Asymmetric Synthesis of Bicyclo[4.3.1] Key Building Blocks","A brief introduction into the chemistry of the CP-molecules is followed by first-generation synthetic sequences toward key building blocks for their total synthesis. Processes for both racemic and enantiomerically enriched bicyclo[4.3.1] ketone 6 or its equivalent are described, and the absolute stereochemistries of the optically enriched intermediates are determined. The efficient route developed to racemic 6 and the ready access to both enantiomers of key building blocks provided the opportunity for the total synthesis of the CP-molecules and determination of their absolute stereochemistry.",10.1021/ja012010l,2002-02-16,0.6229727925724772
Organic Process Research & Development,An Isomerization Approach to Tesirine and Pyrrolobenzodiazepines,"The isomerization of a pyrrolobenzodiazepine (PBD) containing an exo -alkene to one containing an endo -alkene has been demonstrated to prepare a key intermediate for the synthesis of tesirine. This methodology has afforded a shorter formal synthesis of tesirine, delivering a 24-step route compared to the previously reported shortest route of 29 steps. It is anticipated that this methodology will have broader application for converting other PBDs containing exo -alkenes to those containing endo -alkenes.",10.1021/acs.oprd.9b00332,2019-10-24,0.622966592440912
Journal of Organic Chemistry,"Synthesis of 2-(Pyridin-3-yl)-1-azabicyclo[3.2.2]nonane, 2-(Pyridin-3-yl)-1-azabicyclo[2.2.2]octane, and 2-(Pyridin-3-yl)-1-azabicyclo[3.2.1]octane, a Class of Potent Nicotinic Acetylcholine Receptor–Ligands","In an attempt to generate nicotinic acetylcholine receptor (nAChR) ligands selective for the alpha4beta2 and alpha7 subtype receptors we designed and synthesized constrained versions of anabasine, a naturally occurring nAChR ligand. 2-(Pyridin-3-yl)-1-azabicyclo[2.2.2]octane, 2-(pyridin-3-yl)-1-azabicyclo[3.2.2]nonane, and several of their derivatives have been synthesized in both an enantioselective and a racemic manner utilizing the same basic synthetic approach. For the racemic synthesis, alkylation of N-(diphenylmethylene)-1-(pyridin-3-yl)methanamine with the appropriate bromoalkyltetrahydropyran gave intermediates which were readily elaborated into 2-(pyridin-3-yl)-1-azabicyclo[2.2.2]octane and 2-(pyridin-3-yl)-1-azabicyclo[3.2.2]nonane via a ring opening/aminocyclization sequence. An alternate synthesis of 2-(pyridin-3-yl)-1-azabicyclo[3.2.2]nonane via the alkylation of N-(1-(pyridin-3-ylethylidene)propan-2-amine has also been achieved. The enantioselective syntheses followed the same general scheme, but utilized imines derived from (+)- and (-)-2-hydroxy-3-pinanone. Chiral HPLC shows that the desired compounds were synthesized in >99.5% ee. X-ray crystallography was subsequently used to unambiguously characterize these stereochemically pure nAChR ligands. All compounds synthesized exhibited high affinity for the alpha4beta2 nAChR subtype ( K i < or = 0.5-15 nM), a subset bound with high affinity for the alpha7 receptor subtype ( K i < or = 110 nM), selectivity over the alpha3beta4 (ganglion) receptor subtype was seen within the 2-(pyridin-3-yl)-1-azabicyclo[2.2.2]octane series and for the muscle (alpha1betagammadelta) subtype in the 2-(pyridin-3-yl)-1-azabicyclo[3.2.2]nonane series.",10.1021/jo800028q,2008-03-26,0.6229615855851464
Synthesis,Towards the Total Synthesis of 3-Hydroxyvibsanin E,The synthesis of a silyl-protected derivative of 3-hydroxyvibsanin E has been achieved. The key step is a regio-and stereoselective C-H hydroxylation of an advanced tricyclic intermediate by means of a Rubottom oxidation.,10.1055/s-0029-1216912,2009-07-23,0.6229553367996351
Organic Letters,A Concise and Highly Efficient Synthesis of Trehazolin and Trehalamine Starting from <scp>d</scp>-Mannose,"A concise synthesis of trehazolin, its aglycon, trehalamine, and a known analogue has been developed starting from d -mannose. This new approach features a very stereoselective and high-yielding ketone−oxime ether reductive carbocyclization promoted by samarium diiodide as a key step for the preparation of the aminocyclitol component and a mild and very efficient intramolecular triflate displacement reaction for the construction of the oxazoline ring.",10.1021/ol990904t,1999-10-22,0.6229419347685484
European Journal of Organic Chemistry,Revision of the Structure and Total Synthesis of Altenuisol,"Abstract A total synthesis of the reported structure of altenuisol is described. Comparison of the 1 H NMR spectra of the synthesized compound and of the natural product revealed that the originally proposed structure was not correct. Consequently, two constitutional isomers were synthesized. The spectra of one of these compounds – a structure originally proposed as the structure of altertenuol – matched perfectly with the spectra of the natural product. The total synthesis of altenuisol was thus achieved starting with phloroglucinic acid and protocatechuic aldehyde in 10 steps and in 23 % yield, where the longest linear sequence consisted of 6 steps. The key step was a Suzuki coupling with concomitant formation of the lactone ring. Whether altertenuol is identical with altenuisol could not be decided.",10.1002/ejoc.201200506,2012-06-01,0.6229400920975526
Journal of the American Chemical Society,Selective Synthesis of Divergolide I,"Divergolide I (1) is a naphthoquinone ansamycin that exhibits broad antibacterial activity. Its tetracyclic ring system is believed to be biosynthetically assembled via ring contraction of a macrocyclic precursor (proto-divergolide) that is both a macrolactone and a macrolactam. We here report a convergent and enantioselective synthesis that delivers the target molecule in less than 20 linear steps. Our work establishes the absolute configuration of divergolide I, confirms its relative configuration, and demonstrates that the biomimetic cyclization of a proto-divergolide can be surprisingly selective.",10.1021/jacs.7b13092,2018-01-28,0.622938370618463
Organic Letters,An Efficient Chiral Moderator Prepared from Inexpensive (+)-3-Carene:  Synthesis of the HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitor DPC 963,"The beta-amino alcohol 4 beta-morpholinocaran-3 alpha-ol is prepared by addition of morpholine to alpha-3,4-epoxycarane utilizing anhydrous magnesium bromide as Lewis acid promoter. The enantiopure amino alcohol is uniquely effective as a chiral moderator for the addition of lithium cyclopropylacetylide to an unprotected N-acylketimine. This reaction provides an efficient route to the second generation NNRTI drug candidate DPC 963.",10.1021/ol006321x,2000-09-13,0.6229311795172434
Journal of Organic Chemistry,"An Expeditious I<sub>2</sub>-Catalyzed Entry into 6<i>H</i>-Indolo[2,3-<i>b</i>]quinoline System of Cryptotackieine","A synthesis of a series of novel 6H-indolo[2,3-b]quinolines with different substituents on the quinoline ring is described. The method involves reaction of indole-3-carboxyaldehyde with aryl amines in the presence of a catalytic amount of iodine in refluxing diphenyl ether to yield indolo[2,3-b]quinolines in one-pot. The present approach provides a new route for the synthesis of polycyclic structures related to an alkaloid cryptotackieine (neocryptolepine).",10.1021/jo901361x,2009-09-29,0.6229255374304481
Organic Letters,An Unusual Synthesis of <i>N</i>-Unsubstituted Benzazepinones,A short route to novel bicyclic N-unprotected benzazepinones is described starting from N-acetoxyanilides involving radical addition and cyclization with concomitant homolytic rupture of the N-O bond.,10.1021/ol3026044,2012-10-18,0.6229224074570955
European Journal of Organic Chemistry,Enantioselective Synthesis of Cordiachromene,An enantioselective synthesis of cordiachromene is described. An allylic alcohol moiety is first attached in the o-position to the methoxymethoxy substituent in 1-methoxy-4-methoxymethoxybenzene. Then chirality is introduced successively through asymmetric Sharpless epoxidation on the allylic alcohol moiety and regioselective ring-opening. The chiral diol prepared is then cyclized to chromanmethanol with total retention of configuration. Chromenemethanol is obtained after bromination and dehydrobromination. The total synthesis is achieved by reaction between the tosylated chromene chiral moiety and an organomagnesium prenylated compound.,10.1002/1099-0690(200009)2000:18<3223::aid-ejoc3223>3.0.co;2-l,2000-09-01,0.6229217005559038
Organic Letters,Asymmetric Synthesis of the Tricyclooctane Core of Trachylobane Natural Products and Related Terpenoids,"Enantioselective synthesis of a highly versatile building block en route to trachylobanes and related terpenoids is presented. The synthesis features diastereoselective Diels-Alder cycloaddition reaction, a cyclopropanation/homoquadricyclane rearrangement cascade, and palladium-catalyzed C-H acetoxylation. The targeted tricyclooctane was obtained in 20% yield over 8 steps and in 95% ee. The ketone and alcohol functional groups serve as handles for further elaboration.",10.1021/acs.orglett.9b03303,2019-10-11,0.6228470795541875
Journal of Organic Chemistry,Total Synthesis of the Antidiabetic (Type 2) Lipid Mediator Protectin DX/PDX,"The first total synthesis of a lipid mediator derived from natural ω-3-fatty acid docosahexaenoic acid (DHA), 10 S,17 S-diHDHA (also referred to as protectin DX/PDX), was achieved in a convergent route (29 steps). The two chiral hydroxyl groups at C-10 and C-17 were derived from readily available ( S)-1,2,4-butanetriol and ( R)-glycidol, respectively. The two stereodefined E-double bonds were generated by a Takai olefination, and the skipped diene side chain was introduced with a stereocontrolled Wittig olefination. Importantly, the sensitive conjugated E, Z, E-triene intermediate was generated by a Boland reduction of the central triple bond of a E, E-dienyne. Overall, this synthetic strategy should allow the preparation of a larger quantity of PDX, which is inaccessible via previously reported biosynthetic approaches.",10.1021/acs.joc.8b01973,2018-12-26,0.6228348515051538
Synlett,"Total Synthesis of 3,4-Dihydromilbemycin G: Synthesis of the 'Lower Hemisphere' of α-Milbemycins and Avermectins","All articles of this category Closure of the tetrahydrofuran ring via an intramolecular SN2 reaction is the last step in a convergent synthesis of 3,4-dihydromilbemycin G 13 . The hydroxybutenolide 31 has been prepared and converted into the lactone 33 .",10.1055/s-1992-21512,2002-03-08,0.6228219141582441
Journal of Organic Chemistry,Highly Stereocontrolled Formal Synthesis of Brassinolide via Chiral Sulfoxide-Directed S<sub>N</sub>2‘ Reactions,"An efficient stereocontrolled methodology for the preparation of the four contiguous chiral centers of the brassinosteroid side chain is described. Allylic mesyloxy sulfinyl steroids have been found to undergo highly stereoselective S N 2‘ displacements when treated with cyanocuprates that provide the required acyclic stereocontrol in the key C-24 position of the steroidal side chain. Preparation of a direct precursor of brassinolide 1, as well as a precursor of naturally occurring (24 R )-epibrassinolide, (+)-18, is carried out in two additional steps utilizing asymmetric dihydroxylations of (22 E )-olefins (+)-2 and (+)-17 . In this manner, a formal synthesis of this plant growth promoter has been completed, and the extension of the scope of this methodology has been explored providing a straightforward route to this family of steroids. Alternative routes to the key olefin (+)-2 are also outlined. Improved selectivity in the addition to aldehyde 7 for the preparation of the Cram (22 R )-allylic hydroxy sulfoxides is achieved by controlling the chirality at sulfur or by a condensation−symmetric oxidation sequence employing the analogous vinyl sulfide reagent 22 .",10.1021/jo951264k,1996-01-01,0.6227939977473728
Synthesis,"Copper- or Palladium-Catalyzed Amidation and Cyclization Route for the Synthesis of Pyrimido[4,5-b]carbazoles","Pyrimido[4,5- b ]carbazole derivatives were synthesized by a copper- or palladium-catalyzed sequential amidation and cyclization process in which a C–N bond formed at the 2-position of a 3-formylcarbazole afforded a new 9-substituted N -(3-formyl-9 H -carbazol-2-yl)amide.",10.1055/s-0033-1339490,2013-09-02,0.622788022794575
Tetrahedron,The synthesis of 3-(1′-hydroxyethyl)-2-azetidinone-4-yl acetic acid via dianion chemistry - an important intermediate in thienamycin total synthesis,,10.1016/s0040-4039(00)85742-1,1982-01-01,0.6227770110759813
Organic Letters,Synthesis of Cytimidine through a One-Pot Copper-Mediated Amidation Cascade,A concise synthesis of cytimidine was developed utilizing tandem Cu-mediated N-aryl amidations followed by global deprotection. This sequence exploits a regioselective coupling of an iodobenzamide with a halopyrimidine that allows the union of three fragments in a single synthetic manipulation and will permit the efficient and rapid diversification of the cytimidine core.,10.1021/ol2018196,2011-09-13,0.6227729633434623
Journal of Organic Chemistry,Synthesis of the Common Propellane Core Structure of the Hasubanan Alkaloids,The racemic synthesis of the common propellane core structure found in various hasubanan alkaloids is reported. The successful completion hinged upon the stereocontrolled construction of the cis-substituted heterobicycle as a precursor for the intramolecular Dieckmann condensation. A novel strategy is introduced for the facile hydrolysis of a sterically demanding carboxamide under a mild condition. The 2-nitroanilide obtained by the Goldberg arylation of a carboxamide with 2-iodonitrobenzene was readily converted to the corresponding ester derivative by way of N-acylbenzotriazole. We expect that the reported synthetic route will allow the synthesis of a series of hasubanan alkaloids starting from the correspondingly functionalized 2-tetralone derivatives.,10.1021/jo800793s,2008-06-13,0.6227708230492365
Tetrahedron,Highly selective synthesis of hydrazones and indoles from olefins,,10.1016/j.tetlet.2003.11.044,2003-12-09,0.6227639279196951
Angewandte Chemie International Edition,A Second‐Generation Total Synthesis of Spirastrellolide A Methyl Ester,"Marine macrolides: an improved second-generation total synthesis of the anticancer macrolide spirastrellolide A methyl ester has been achieved. The synthesis features a uniformly high level of stereocontrol combined with more expedient fragment assembly, and demonstrates a critical dependence of the crucial macrolactonization step on the substitution pattern of the C22-C24 linker region.",10.1002/anie.201108594,2012-02-06,0.6227633188394917
Synlett,A 16-Step Total Synthesis of Norzoanthamine,"Abstract Herein, we present a 16-step synthetic route to norzoanthamine that features three pivotal photochemical transformations. A photoinduced dearomative 6π-desymmetrization is employed to access the ABC tricyclic core structure. To address the challenge of constructing the C9–C22 vicinal all-carbon quaternary stereocenters, [2+2]-photocycloaddition, visible-light-induced decarboxylative borylation, and a retro-aldol reaction are strategically employed. The assembly of the norzoanthamine core framework is achieved through a one-pot cascade transformation, combining global deprotection, biomimetic cyclization, and epimerization at C21, resulting in an efficient and concise synthesis of norzoanthamine. 1 Introduction 2 Total Synthesis of Norzoanthamine 3 Conclusion",10.1055/s-0043-1773532,2025-04-09,0.6227611393679009
European Journal of Organic Chemistry,A New Access to Diarylmaleic Anhydrides,"A new three-step synthesis of diarylmaleic anhydrides 6, starting from 3-aryl-2-hydroxybut-2-enedioates 2, is reported.",10.1002/(sici)1099-0690(199906)1999:6<1421::aid-ejoc1421>3.0.co;2-o,1999-06-01,0.6227606489100491
Organic Process Research & Development,Process Development of (2-Nitrophenylcarbamoyl)-(<i>S</i>)-prolyl-(<i>S</i>)-3- (2-naphthyl)alanyl-<i>N</i>-benzyl-<i>N</i>-methylamide (SDZ NKT343),"(2-Nitrophenylcarbamoyl)-( S )-prolyl-( S )-3-(2-naphthyl)alanyl- N -benzyl- N -methylamide ( 1; SDZ NKT343) is a human NK-1 tachykinin receptor antagonist. The development of a robust process for a multikilogram scale, chromatography-free preparation of this compound is described. The new four-step synthesis was based on a convergent approach, which utilized a peptide coupling of 1-[(2-nitrophenylamino)carbonyl]- l -proline ( 11 ) with free base of ( S )-3-(2-naphthyl)alanyl- N -benzyl- N -methylamide hydrochloride ( 4 ) as the key step in the presence of 1,3-dicyclohexylcarbodiimide and 1-hydroxybenzotriazole as coupling agents. A scale-up of the well-known mixed anhydride coupling method, using isobutyl chloroformate, to produce 4 was found to be problematic due to coupling of the amine at the undesired carbonyl group of the mixed anhydride. This problem was overcome. The drug substance, initially an amorphous powder, was obtained with the desired purity without any chromatography. A process for crystallization of 1 was also developed.",10.1021/op990188a,1999-08-26,0.6227601581261715
Organic Letters,A Total Synthesis of Millingtonine A,"A total synthesis of millingtonine A, a diglycosylated alkaloid, has been accomplished. Millingtonine A possesses a unique racemic tricyclic core structure not known from any other natural or synthetic source until now. The synthesis features a key bond-forming radical Ueno-Stork cyclization to form the heterocyclic core.",10.1021/ol203158p,2012-01-19,0.622759306542139
Angewandte Chemie International Edition,Total Synthesis of Leucosceptroids A and B,"Leucosceptroids A and B are sesterterpenoids with potent antifeedant and antifungal activities. A more efficient gram-scale total synthesis of leucosceptroid B and the first total synthesis of leucosceptroid A are presented. The key transformations include an aldol reaction between a substituted dihydrofuranone and an (S)-citronellal-derived aldehyde, a SmI2-mediated intramolecular ketyl-olefin radical cyclization, and final-stage alcohol oxidation.",10.1002/anie.201410134,2014-12-03,0.6227556297387979
Organic Letters,Rapid and Efficient Synthesis of 1<i>H</i>-Indol-2-yl-1<i>H</i>-quinolin-2-ones,[reaction: see text] A concise and efficient synthesis of the novel indol-2-yl-1H-quinolin-2-one ring system found in the potent and selective KDR kinase inhibitors 1-3 is presented.,10.1021/ol035541i,2003-09-25,0.6227484293245346
Organic Process Research & Development,Identification and Control of Critical Process Impurities: An Improved Process for the Preparation of Dolutegravir Sodium,"A four-stage manufacturing route for the preparation of dolutegravir sodium ( 1 ) was assessed and optimized leading to a higher yielding, simpler and scalable process. Key improvements in the process include the development of mild workup procedure by selective derivatization of a difficult to remove a process impurity using tert -butyldimethylsilyl chloride. Metal-based hydrogenation-free O -debenzylation is optimized, and the critical isomeric impurity formed was identified and eliminated from the process by the establishment of a proper control strategy.",10.1021/acs.oprd.6b00156,2016-07-18,0.6227434718665953
Journal of Organic Chemistry,Asymmetric [C + NC + CC] Coupling Entry to the Naphthyridinomycin Natural Product Family: Formal Total Synthesis of Cyanocycline A and Bioxalomycin β2,"A full account of our [C + NC + CC] coupling approach to the naphthyridinomycin family of natural products is presented, culminating in formal total syntheses of cyanocycline A and bioxalomycin β2. The key complexity-building reaction in the synthesis involves the Ag(I)-catalyzed endo-selective [C + NC + CC] coupling of aldehyde 7, (S)-glycyl sultam 8, and methyl acrylate (9) to provide the highly functionalized pyrrolidine 6, which was carried forward to an advanced intermediate (compound 33) in Fukuyama's synthesis of cyanocycline A. Since cyanocycline A has been converted to bioxalomycin β2, this constitutes a formal synthesis of the latter natural product as well. The multicomponent reaction-based strategy reduces the number of steps previously needed to assemble these complex molecular targets by one-third. This work highlights the utility of the asymmetric [C + NC + CC] coupling reaction in the context of a complex pyrrolidine-containing target and provides an illustrative guide for its application to other synthesis problems. The synthesis also fueled collaborative biological and biochemical research that identified a unique small molecule inhibitor of cell migration (compound 30).",10.1021/jo200553g,2011-05-31,0.6227409692660886
Tetrahedron,Synthesis of photoactive DNA: incorporation of 8-bromo-2′-deoxyadenosine into synthetic oligodeoxynucleotides,,10.1016/s0040-4039(00)74234-1,1992-07-01,0.6227345918533236
Tetrahedron,Preparation involving a C4-C3 ring contraction in the key step of a novel cyclopropane carbocyclic nucleoside,,10.1016/0040-4039(95)01536-1,1995-10-01,0.6227344924659866
European Journal of Organic Chemistry,Asymmetric Synthesis of Crispine A: Constructing Tetrahydroisoquinoline Scaffolds Using Pummerer Cyclizations,"Abstract For the first time, a concise, linear and stereoselective synthesis of both enantiomers of the natural product crispine A has been achieved in six steps with an overall yield of ≥ 20 %, starting from commercially available veratraldehyde. Asymmetric Keck allylation and trifluoroacetic anhydride‐mediated Pummerer cyclization were the key transformations used to construct the tetrahydroisoquinoline core structure.",10.1002/ejoc.201300748,2013-08-12,0.6227326007650317
Journal of Organic Chemistry,"Total Synthesis of (−)-Citreoisocoumarin, (−)-Citreoisocoumarinol, (−)-12-<i>epi</i>-Citreoisocoumarinol, and (−)-Mucorisocoumarins A and B Using a Gold(I)-Catalyzed Cyclization Strategy","A unified and concise first asymmetric total synthesis of (−)-citreoisocoumarin ( 2 ), (−)-citreoisocoumarinol ( 3 ), 12- epi -citreoisocoumarinol ( 4 ), and (−)-mucorisocoumarins A ( 5 ) and B ( 6 ) have been accomplished from the common intermediate (−)-6- O -methyl-citreoisocoumarin ( 1 ). Central to the synthetic approach is a regioselective gold(I)-catalyzed 6- endo - dig cyclization strategy for the construction of the isocoumarin skeleton. The other key steps in this approach included Sonogashira coupling, Tsuji-Wacker oxidation, Evans-Saksena’s 1,3- anti -reduction, and Narasaka-Prasad’s 1,3- syn -reduction. The synthetic results unambiguously confirmed the absolute configuration of the natural products mucorisocoumarins A and B as (−)-(10 R,12 S )- 5 and (+)-(10 S,12 S )- 6, respectively.",10.1021/acs.joc.9b03278,2020-02-26,0.6227319962421815
Journal of Organic Chemistry,Synthesis of (±)-Serralongamine A and the Revised Structure of Huperzine N,"A revised structure for the Lycopodium alkaloid huperzine N is proposed and confirmed by synthesis. The key synthetic steps involve an epimerization of a cis-5-oxodecahydroquinoline to the corresponding trans isomer and a coupling, followed by a diastereoselective hydrogenation using Wilkinson's catalyst to incorporate the pyridylmethyl moiety. This route allowed the alkaloid serralongamine A to be synthesized for the first time, and two additional steps led to the revised structure of huperzine N, both products bearing an unusual decahydroquinoline stereostructure.",10.1021/acs.joc.6b00025,2016-03-01,0.6227188410157275
Chemical Science,A synthesis of strychnine by a longest linear sequence of six steps,"Strychnine is synthesized via a longest linear sequence of six steps from commercially available starting materials. Key steps include a base-mediated intramolecular Diels–Alder reaction of a tryptamine-derived Zincke aldehyde, a Ru-catalyzed trans-hydrosilylation of 1,4-butynediol, and a tandem Brook rearrangement/intramolecular conjugate addition reaction that affords the Wieland–Gumlich aldehyde.",10.1039/c1sc00009h,2011-01-01,0.6227126360957446
Angewandte Chemie International Edition,Novel Strategy for the Synthesis of the Butenolide Moiety of Peridinin,"Tartaric acid is the starting point for the stereoselective synthesis of the butenolide unit (see scheme)in peridinin, a marine carotenoid. Key steps were the desymmetrization of tartaric acid bis(Weinreb amide), an E-selective olefination by Ando-type bromophosphonates, and an anti-selective Mitsunobu elimination (for establishing the C1′Cγ bond).",10.1002/anie.200460259,2005-01-28,0.6226939089661662
Angewandte Chemie International Edition,Rapid Construction of the Cortistatin Pentacyclic Core,"Ringing in cortistatin: The pentacyclic core of the cortistatin steroidal alkaloids has been readily assembled in eleven steps from simple building blocks (see scheme; PMB=para-methoxybenzyl, TBS=tert-butyldimethylsilyl). An enyne cycloisomerization and an oxidative dearomatization/cyclization are the key ring-forming steps in this sequence.",10.1002/anie.200802203,2008-07-18,0.6226885997549761
Tetrahedron,Synthesis of the host-selective phytotoxin destruxin B. Avoiding diketopiperazine formation from an N-methyl amino acid dipeptide by use of the Boc-hydrazide derivative,,10.1016/s0040-4039(96)02346-5,1997-01-01,0.6226826181596509
Angewandte Chemie International Edition,Catalysis‐Enabled Concise and Stereoselective Total Synthesis of the Tricyclic Prostaglandin D<sub>2</sub> Metabolite Methyl Ester,"Abstract A concise and stereoselective total synthesis of the clinically relevant tricyclic prostaglandin D 2 metabolite (tricyclic‐PGDM) methyl ester in racemic form was accomplished in eight steps from a readily available known cyclopentene‐diol derivative. The synthesis features a nickel‐catalyzed Ueno–Stork‐type dicarbofunctionalization to generate two consecutive stereocenters, a palladium‐catalyzed carbonylative spirolactonization to build the core oxaspirolactone, and a Z ‐selective cross‐metathesis to introduce the ( Z )‐3‐butenoate side chain, a group challenging to introduce through traditional Wittig protocols and troublesome for the two previous total syntheses. A general Z ‐selective cross‐metathesis protocol to construct ( Z )‐β,γ‐unsaturated esters was also developed that has broad functional group tolerance and high stereoselectivity. Additionally, our synthesis already accumulated 75 mg of valuable material for an 18 O‐tricyclic‐PGDM‐based assay used in clinical settings for inflammation.",10.1002/anie.202115633,2021-12-06,0.6226772804973949
Synthesis,"New [<i>f</i>]-Fused Theophyllines: A Simple One-Step Synthesis of the Pyrimido[2,1-<i>f</i>]purine System via 8-Azidopurines","All articles of this category An approach to novel tetrahydro- and hexahydropyrimido[2,1- f ] purines starting from 7-(2-alkenyl)- or 7-(2-alkynyl)-8-azidotheophyllines is described.",10.1055/s-1989-27355,1989-01-01,0.6226770164977571
European Journal of Organic Chemistry,First Efficient Synthesis of Chlorogenic Acid,"The first efficient synthesis of chlorogenic acid (1) was achieved in four steps (three purifications) from quinic acid (2). The overall yield was 65%. The key intermediate was quinic acid bisacetonide (6), selectively prepared by a modified kinetic acetalization protocol. Esterification of 6 with caffeic acid chloride (3) afforded ester 12. Cleavage of all the protecting groups of 12 was accomplished in one step under acidic conditions. The progress of the hydrolysis was monitored by MALDI-MS.",10.1002/1099-0690(200103)2001:6<1137::aid-ejoc1137>3.0.co;2-2,2001-03-01,0.6226767779913306
Journal of the American Chemical Society,Stereocontrolled Synthesis of (−)-Macrolactin A,"The total synthesis of (-)-macrolactin A, a 24-membered macrolide, has been achieved using a newly developed 1,3-diol synthon for the introduction of two key stereogenic centers. The synthon was derived from sequential use of the Noyori asymmetric reduction followed by chiral sulfoxide methodology. Tellurium-derived cuprate organometallics offered an efficient and highly stereoselective means for installation of the C8 Z/E-diene, while the C15 E/E-segment was derived from a Julia-Lythgoe olefination. Yamaguchi lactonization was used to secure the macrocycle in a convergent approach with the longest linear sequence of 19 steps from Noyori alcohol 6.",10.1021/ja017177t,2002-01-31,0.622676024409365
Synlett,Total Synthesis of Dictyodendrillin-B,"All articles of this category Dictyodendrillin-B ( 1 ), an oxygenated sesquiterpene of marine origin, as well as methoxyacetal 2 have been prepared by a concise route (6 steps, 43% overall yield). marine natural product - oxygenated sesquiterpenes - heteroprostanoids - 2(5 H )-furanones - aza-aldol reaction",10.1055/s-1998-1723,1998-06-01,0.6226460075008339
Tetrahedron,"Synthesis of3,4-dihydro-4-methyl-2-(quinolin-3-yl)-2H-pyrano[3,2-c]quinolines",,10.1016/s0040-4039(00)86720-9,1988-01-01,0.6226412299793034
European Journal of Organic Chemistry,Synthesis of a D Ring‐Functionalized Derivative of the Epiwelwistatin Tetracyclic Core,Abstract A 14‐oxo derivative of the tetracyclic core of the alkaloid 3‐ epi ‐welwistatin was prepared by a regioselective ring expansion of Kornfeld's ketone followed by a Michael‐intramolecular aldol anionic domino process to generate a tetracyclic system that contained a bicyclo[4.3.1]decane fragment fused to an indole. Treating this compound with N ‐bromosuccinimide in tert ‐butyl alcohol diastereoselectively generated the oxindole ring that is inherent to the natural product.,10.1002/ejoc.201201747,2013-03-19,0.6226392481168825
European Journal of Organic Chemistry,"Enantioselective Synthesis of Ozanimod, the Active Pharmaceutical Ingredient of a New Drug for Multiple Sclerosis","Abstract We report here a short enantioselective synthesis of Ozanimod, a potent modulator of the enzyme Sphingosine‐1‐phosphate receptor (S1P R ), recently approved by FDA and EMA for the treatment of relapsing‐remitting multiple sclerosis. Amongst different synthetic approaches explored, we achieved the best result introducing the stereogenic centre in the last step through imine asymmetric transfer hydrogenation (ATH) using Wills’ catalysts. Besides the reduced numbers of enantiomeric purity controls required, this process culminates in an exceptionally high enantioselective reductive amination obtained with commercially available tethered Ru catalysts. Starting from commercially available 4‐cyano‐indanone, enantiomerically pure Ozanimod was obtained in 5 steps in 62 % overall yield and 99 % ee.",10.1002/ejoc.202100058,2021-03-07,0.6226360870162162
Synlett,Enyne Metathesis Approach towards the Cyclopentane Motif of Jatrophane Diterpenes,"A short and efficient synthesis of the cyclopentane moiety of the jatrophane diterpene Pl-3 has been developed. The route features an enyne metathesis reaction, and a stereoselective palladium-catalyzed reductive epoxide opening as key steps.",10.1055/s-0033-1339923,2013-10-28,0.6226185377770754
Organic Letters,A New Total Synthesis of the Marine Tunicate Alkaloid Lepadiformine,[reaction: see text]. A total synthesis of racemic lepadiformine has been achieved via a route that utilizes as key steps a novel stereocontrolled intramolecular spirocyclization of an allylsilane/N-acyliminium ion and the application of our radical-based methodology for production of N-acylimines from o-aminobenzamides.,10.1021/ol010179y,2001-10-02,0.6226126763121841
Journal of Organic Chemistry,Stereoselective Synthesis of Baloxavir Marboxil Using Diastereoselective Cyclization and Photoredox Decarboxylation of <scp>l</scp>-Serine,"Baloxavir marboxil ( 1; BXM) is a potent drug used for treating influenza infections. The current synthetic route to BXM ( 1 ) is based on optical resolution; however, this method results in the loss of nearly 50% of the material. This study aimed to describe an efficient and simpler method for the synthesis of BXM. We achieved a stereoselective synthesis of BXM ( 1 ). The tricyclic triazinanone core possessing a chiral center was prepared via diastereoselective cyclization utilizing the readily available amino acid l -serine. The carboxyl moiety derived from l -serine was removed via photoredox decarboxylation under mild conditions to furnish the chiral tricyclic triazinanone core (( R )- 14 ). The synthetic route demonstrated herein provides an efficient and atomically economical method for preparing this potent anti-influenza agent.",10.1021/acs.joc.4c00799,2024-07-10,0.6226113079278794
Synlett,Total Synthesis of Avermectin B1a: Final Coupling Reactions and the Total Synthesis of Avermectin B1a Aglycone,All articles of this category Synthesis of the avermectin B1a aglycone ( 3 ) involving sulphone stabilised anion coupling of a C1-C10 fragment 1 with C11-C25 spiroacetal portion 2 is described. The synthesis exploits chemoselectivity in an effort to minimise the need for functional group protection.,10.1055/s-1990-21080,1990-01-01,0.6226111402150805
Journal of Organic Chemistry,Zeolite NaY-Promoted Cyclization of Farnesal:  A Short Route to Nanaimoal,"The sesquiterpene nanaimoal was synthesized in 21% overall yield and in a biomimetic manner. As a key step, the acid-catalyzed cyclization of farnesal under zeolite NaY confinement conditions was used. The intrazeolite cyclization of farnesal affords as major product a double-bond isomer of nanaimoal, via a novel diastereoselective tandem 1,5-diene cyclization/Prins-type reaction.",10.1021/jo7024527,2008-03-06,0.6225985924189417
Journal of the American Chemical Society,Concise Total Syntheses of the 6–7–5 Hamigeran Natural Products,"Herein, we report the total syntheses of four hamigeran natural products featuring a 6-7-5 tricyclic carbon skeleton. We utilized a palladium-catalyzed intramolecular cyclopropanol ring opening cross-coupling to build the central seven-membered ring and a series of oxidations including a challenging aromatic C-H oxidation to introduce the peripheral functionalities. This approach enabled us to achieve the first total syntheses of hamigeran C (14 steps), debromohamigeran I (12 steps), and hamigeran I (13 steps). Our synthesis also resulted in hamigeran G in 13 steps, which is significantly shorter than the previously reported one (24 steps, longest linear sequence).",10.1021/jacs.3c06031,2023-08-21,0.6225965659904842
Synthesis,A Synthetic Route to the MT1-MMP Inhibitor Ancorinoside D,"A methyl ester of ancorinoside D, a 3-acyltetramic acid metabolite of a sponge Penares sollasi, was synthesised in ten steps starting from a protected β-d-glucopyranosyl-(1→4)-d-galactopyranosyltrichloroacetimidate donor. Its attachment to the left half of the 3-acyl spacer by a Schmidt glycosylation, 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO)-mediated oxidation to the uronic acid, introduction of the Z-alkene via Wittig reaction, and functionalisation of the spacer terminus with Meldrum’s acid gave a β-keto ester that reacted with dimethyl N-methyl-d-aspartate under neutral conditions to afford a fully protected ancorinoside D as the product of an unusual domino N-acylation–Dieckmann condensation. Global deprotection left a methyl ester of ancorinoside D, which resisted all saponification attempts.",10.1055/s-0037-1610287,2018-09-26,0.6225951798318566
Journal of the American Chemical Society,Total Synthesis of (+)-Frondosin A. Application of the Ru-Catalyzed [5+2] Cycloaddition,"The first total synthesis of (+)-frondosin A was accomplished in 19 longest linear and 21 total steps from commercially available materials. The key features of the synthesis include a Ru-catalyzed [5+2] cycloaddition, a Claisen rearrangement, and a ring expansion to construct the core of the frondosin A in a diastereoselective and regioselective fashion. This is the first application of a Ru-catalyzed [5+2] cycloaddition in the total synthesis of a natural product. Through this synthesis, the absolute configuration of (+)-frondosin A was established.",10.1021/ja073272b,2007-08-31,0.6225889580927108
Organic Letters,Modular Synthesis of Candidate Indole-based Insulin Mimics by Claisen Rearrangement,"A modular synthetic route to (indolyl)kojic acid anti-diabetes agents has been developed. Sonogashira coupling of a protected iodoaniline with a propargyl kojate was used to construct an (indole)methyl kojate. Its heteroaromatic Claisen rearrangement, followed by tautomerization to return the indole and pyrone rings, was used to create the biaryl C-C bond. This route should enable collections of insulin mimic drug candidates to be prepared from a few basic building blocks.",10.1021/ol800058d,2008-02-28,0.6225650382627455
Journal of the American Chemical Society,Total Synthesis of Hyperforin,"A 10-step total synthesis of the polycyclic polyprenylated acylphloroglucinol (PPAP) natural product hyperforin from 2-methylcyclopent-2-en-1-one is reported. This route was enabled by a diketene annulation reaction and an oxidative ring expansion strategy designed to complement the presumed biosynthesis of this complex meroterpene. The described work enables the preparation of a highly substituted bicyclo[3.3.1]nonane-1,3,5-trione motif in only six steps and thus serves as a platform for the construction of easily synthesized, highly diverse PPAPs modifiable at every position.",10.1021/jacs.5b06939,2015-08-07,0.622558421541796
Organic Process Research & Development,Practical Alternative Synthesis of 1-(8-Fluoro-naphthalen-1-yl)piperazine,"Convergent synthesis of 8-fluoronaphthalen-1-ylamine ( 6 ) was achieved through the reaction of 1 H -naphtho[1,8- de ][1,2,3]triazine ( 15 ) with HF-pyridine under mild conditions. This new synthesis for the preparation of 6 overcame many scale-up challenges that exist in the methods reported in the literature and provided a practical alternative synthesis of 1-(8-fluoronaphthalen-1-yl)piperazine ( 1 ).",10.1021/op7001535,2007-08-21,0.6225555716497474
Organic Letters,A New Cobalt–Salen Catalyst for Asymmetric Cyclopropanation. Synthesis of the Serotonin–Norepinephrine Repuptake Inhibitor (+)-Synosutine,"A new C2 symmetric cobalt(II)-salen catalyst based on cis-2,5-diaminobicyclo[2.2.2]octane as the chiral scaffold was prepared which, in the presence of potassium thioacetate as the promoter, catalyzed the formation of cyclopropanes from 1,1-disubstituted ethylenes and ethyl diazoacetate in high yield and with excellent diastereo- and enantioselectivity. Asymmetric cyclopropanation with the catalyst was used in a short, efficient synthesis of the dual serotonin-epinephrine reuptake inhibitor (+)-synosutine.",10.1021/ol501549x,2014-07-14,0.6225540241388695
Synlett,Total Synthesis of (+)-Fumiquinazoline G and (+)-Dehydrofumiquinazoline G,All articles of this category An efficient twelve step synthesis of (+)-fumiquinazoline G ( 16 ) has been accomplished in 11% overall yield. aza-Wittig reaction - diketopiperazine - methylenediketopiperazine immunosuppressants - fumiquinazolines,10.1055/s-1997-6137,1997-06-01,0.6225391559932467
Journal of Organic Chemistry,"Total Synthesis of (<i>S</i>)-(−)-(<i>E</i>)-15,16-Dihydrominquartynoic Acid: A Highly Potent Anticancer Agent","The conjugated entriyne natural product, (S)-(E)-15,16-dihydrominquartynoic acid (1), is synthesized in five linear steps and 30% overall yield from the known aldehyde 11. The key step is a one-pot in situ desilylation/Cadiot-Chodkiewicz coupling reaction affording the entriyne unit. The bromoalkyne 6 with an omega-carboxylic acid group was found to undergo a copper-catalyzed cross-coupling reaction producing the desired diyne intermediate 10, while the corresponding omega-ester bromoalkyne 14 failed to couple with triethylsilylacetylene under a variety of conditions.",10.1021/jo049920g,2004-04-20,0.622537328959068
Organic Letters,Synthesis of Novel Polycyclic Indolyldiamines,"A rapid and stereoselective access to novel polycyclic indolyldiamines is described. The key step involves simple chemoselective transformations of a common bicyclic aminal intermediate, easily available on a large scale from an enantiomerically pure cyano oxazolopiperidine precursor.",10.1021/ol047408b,2005-04-22,0.6225372056531391
Tetrahedron,Novel diastereoselective routes for the synthesis of the ambergris ketals,,10.1016/s0040-4039(00)78512-1,1994-11-01,0.6225314391084188
Tetrahedron,A new practical method for the synthesis of acetylenes.,,10.1016/s0040-4039(00)92375-x,1991-09-01,0.6225248794189439
Journal of Organic Chemistry,A Concise Route to Orthogonally Protected Bulgecinine,"Bulgecinine is the core structure for inhibitors of the important lytic transglycosylases of bacterial cell-envelope homeostasis. Their central pyrrolidine ring mimics, as the protonated amine, the transient oxocarbenium species of the enzymatic reaction. We report a concise synthesis of protected bulgecinine 9 (nine linear steps and 12% overall yield). The key step is the vinyl Grignard addition to a nitrone (pyrrolidine- N -oxide) intermediate. Compound 9 possesses the correct absolute stereochemistry of the three stereogenic centers, validated by an X-ray structure.",10.1021/acs.joc.5c02804,2025-12-23,0.6225222411272464
Journal of Organic Chemistry,Synthesis and Determination of Absolute Configuration of α-Pyrones Isolated from <i>Penicillium corylophilum</i>,"The first total synthesis of (S)-6-(2,9-dihydroxynonyl)-4-hydroxy-3-methyl-2H-pyran-2-one, 4-hydroxy-3-methyl-6-((2S,4R)-2,4,11-trihydroxyundecyl)-2H-pyran-2-one, and its unnatural 2R,4R-isomer starting from commercially available 1,8-octanediol is described. The synthesis led to the revision of the proposed structural assignment of the natural product as (R)-6-(2,9-dihydroxynonyl)-4-hydroxy-3-methyl-2H-pyran-2-one. The key steps include chiral auxiliary mediated asymmetric acetate aldol reaction, dianion addition, and base mediated cyclization to form an α-pyrone ring.",10.1021/jo5015382,2014-10-22,0.6225221735302888
Journal of the American Chemical Society,Enantioselective Total Synthesis of Clavirolide C. Applications of Cu-Catalyzed Asymmetric Conjugate Additions and Ru-Catalyzed Ring-Closing Metathesis,"The first enantioselective total synthesis of clavirolide C, a member of the dolabellane family of diterpenes isolated from Pacific soft coral Clavularia viridis, is disclosed. The total synthesis features the application of chiral amino acid based ligands in Cu-catalyzed asymmetric conjugate addition (ACA) reactions and a relatively rare application of catalytic ring-closing metathesis to access an 11-membered ring structure. The total synthesis effort has spawned the development of a new protocol for NHC.Cu-catalyzed ACA of alkylaluminum reagents to beta-substituted cycloalkenones. The enantioselective clavirolide C synthesis requires 17 steps (longest linear sequence), affords the target molecule in 3.5% overall yield, and confirms the stereochemical assignment for the natural product.",10.1021/ja8058414,2008-09-09,0.6225132635299592
Synlett,"First Total Syntheses of (3R,5R)-Sonnerlactone and (3R,5S)-Sonnerlactone","First total syntheses of the macrocyclic natural products (3R,5R)-sonnerlactone and (3R,5S)-sonnerlactone, two new metabolites isolated from the endophytic fungus strain Zh6-B1, have been accomplished in eleven steps with 22% overall yield starting from enantiomerically pure (R)-propylene oxide prepared by hydrolytic kinetic resolution. Other key steps are Sharpless epoxidation, reductive elimination of iodo epoxide, and ring-closing-metathesis reaction for the construction of the macrolactone.",10.1055/s-0031-1289529,2011-10-19,0.6225120480691376
Journal of Organic Chemistry,Total Syntheses of Five Indole Alkaloids from the Marine Bryozoan <i>Flustra </i><i>f</i><i>oliacea</i>,"A general, efficient, and conceptually new approach to the total syntheses of marine-derived indole alkaloids, including (+/-)-flustramines A (1) and B (2), (+/-)-flustramides A (3) and B (4), and (+/-)-debromoflustramine B (5), is outlined. The key step in the syntheses involves the conjugated addition of an organomagnesium species derived from prenyl bromide to 2-hydroxyindolenines. Compounds 1, 2, and 5 have been synthesized in five steps with 23%, 17%, and 16% overall yield, respectively, whereas flustramides 3 and 4 have been synthesized in only four steps with 24% and 18% overall yield, respectively, on the basis of 2-hydroxyindolenines.",10.1021/jo0012647,2001-01-27,0.6225017222058977
Synthesis,"A Practical, Laboratory-Scale Synthesis of Perampanel","The orally active, noncompetitive, selective AMPA receptor antagonist Perampanel, 2-[1′,6′-dihydro-6′-oxo-1-phenyl-(2′,3′-bipyridin)-5′-yl]benzonitrile, has been prepared from readily available, relatively inexpensive starting materials. The synthesis was carried out on a laboratory scale with no specialized equipment, and involved only two chromatographic purifications.",10.1055/s-0031-1289587,2011-11-04,0.6224973677510859
Journal of Organic Chemistry,First Enantiospecific Synthesis of (−)-Parvifoline and (−)-Curcuquinone,"The first enantiospecific synthesis of (-)-parvifoline, employing ring-closing metathesis as the key step, and (-)-curcuquinone from naturally occurring (R)-(+)-citronellal is described.",10.1021/jo061730d,2006-10-13,0.6224970560092481
Organic Letters,"Synthesis of Islatravir Enabled by a Catalytic, Enantioselective Alkynylation of a Ketone","The synthesis of the potent anti-HIV investigational treatment islatravir is described. The key step in this synthesis is a highly enantioselective catalytic asymmetric alkynylation of a ketone. This reaction is a rare example of the asymmetric addition of an alkyne nucleophile to a ketone through ligand-accelerated catalysis that was performed on a greater than 100 g scale. By leveraging a multienzyme cascade, a highly diastereoselective aldol-glycosylation was used to complete the target in eight steps.",10.1021/acs.orglett.0c01431,2020-06-09,0.6224921552974731
Tetrahedron,Highly efficient synthesis of 2′-O-amino nucleosides and their incorporation in hammerhead ribozymes,,10.1016/s0040-4039(97)10784-5,1998-03-01,0.6224656708531476
Synthesis,A Facile Synthesis of a Key Intermediate for (+)-Biotin via Strecker Reaction,"The Strecker reaction of (2R,4R)-2-phenyl-3-phenoxycarbonylthiazolidine-4-carbaldehyde (4b), which was readily prepared from l-cysteine, with benzylamine and trimethylsilyl cyanide provided α-amino nitrile 5b stereoselectively (syn-anti, 2:1). Amidation of 5b and subsequent cyclization gave bicyclic compound 6, which, upon reduction with zinc dust, hydrolysis and subsequent cyclization, furnished thiolactone 2, a key intermediate for (+)-biotin (1).",10.1055/s-2003-42399,2003-01-01,0.6224598907616301
Organic Process Research & Development,Efficient Large Scale Preparation of Neutral Endopeptidase/Angiotensin-Converting Enzyme Dual Inhibitor CGS30440,"The development and piloting of a potential manufacturing process for ACE/NEP dual inhibitor CGS30440 is described. The synthesis proceeds sequentially from 1-aminocyclopentanecarboxylic acid via N-protection, peptide coupling with l -tyrosine ethyl ester, O-methylation of N-protected [(1-amino-1-cyclopentyl)carbonyl]- l -tyrosine ethyl ester, N-deprotection, peptide coupling of [(1-amino-1-cyclopentyl)carbonyl]- O -methyl- l -tyrosine ethyl ester with d -2-bromo-3-methylbutyric acid, and final displacement of bromide with thioacetate. This approach is superior to shorter Discovery routes based upon final peptide coupling of l -2-(acetylthio)-3-methylbutanoic acid to [(1-amino-1-cyclopentyl)carbonyl]- O -methyl- l -tyrosine ethyl ester.",10.1021/op970242s,1998-05-02,0.6224532731831783
Journal of Organic Chemistry,Selective Synthesis of <i>m</i><i>eso</i>-Naphthylporphyrins,"A series of novel meso-(8-substituted naphth-1-yl)porphyrins has been synthesized creating derivatives with a tight recognition environment above the porphyrin plane. The selective synthesis of single atropisomers is discussed. Condensation of bisnaphthaldehyde 12 with phenyldipyrromethane unexpectedly led to selective synthesis of the alpha,alpha-5,10-bridged isomer 14. A mechanism is proposed for this unusual scrambling, and alternative syntheses of alpha,alpha-5,15-bisnaphthylporphyrins are described. Synthesis of 5,15-analogues can be achieved by employing (pentafluorophenyl)dipyrromethane or via presynthesis of a bis(dipyrromethane) derivative 22 (from bisnaphthaldehyde 12) and subsequent condensation with benzaldehyde.",10.1021/jo0260488,2002-09-24,0.6224530450692224
Journal of Organic Chemistry,Formal Synthesis of (−)-Quinagolide: Diastereoselective Ring Expansion via a Bicyclic Aziridinium Ion Strategy to Access the Octahydrobenzo[<i>g</i>]quinoline Architecture,"receptor agonist, has been achieved. The synthesis started from l-pyroglutamic acid and relied on utilization of (a) a stereospecific catalytic hydrogenation and diastereoselective Horner-Emmons-Michael cascade to obtain functionalized prolinate, (b) a Lewis acid mediated Pummerer cyclization to construct a tricyclic fused ring system, and (c) a diastereoselective ring expansion via a bicyclic aziridinium intermediate to access the required 3-substituted piperidine scaffold.",10.1021/acs.joc.1c00603,2021-07-06,0.6224523924622212
Organic Letters,"Improved and Efficient Synthesis of Chiral N,P-Ligands via Cyclic Sulfamidates for Asymmetric Addition of Butyllithium to Benzaldehyde","A robust and scaleable route to chiral 1-isopropylamino-2-(diphenylphosphino)ethanes is described via the ring-opening of chiral, cyclic sulfamidates with potassium diphenylphosphide (KPPh(2)). The novel protocol offers a robust access to gram quantities of chiral amino phosphinoethanes in high yields. The Li-amides of the chiral aminophosphines were evaluated as chiral ligands in the asymmetric addition of n-butyllithium (BuLi) to benzaldehyde, yielding 1-phenylpentanol up to 98% ee.",10.1021/ol701504c,2007-08-16,0.6224425858275332
Synlett,Enantioselective Formal Total Synthesis of Damsin,"Abstract Enantioselective formal total synthesis of damsin, which was isolated from Compositae Ambrosia maritima L., is described. The highly enantio- and diastereoselective catalytic Mukaiyama–Michael reaction and subsequent highly stereoselective epimerization shorten the synthetic steps. It is also reported that the enolate, which was formed by the reaction of β-keto sulfone with lithium naphthalenide, reacted with methyl cyanoformate to form a quaternary stereogenic center in high yield with high stereoselectivity. This finding extends the synthetic chemistry starting from β-keto sulfones.",10.1055/a-2017-3636,2023-01-20,0.6224367552786783
Journal of Organic Chemistry,Reactive Enols in Synthesis 2. Synthesis of (+)-Latifolic Acid and (+)-Latifoline,"We describe a short, enantioselective synthesis of the naturally occurring pyrrolizidine alkaloid (+)-latifoline (1) employing a tandem [3,3] sigmatropic rearrangement/[1,2] allyl shift as a key step in constructing (+)-latifolic acid (4).",10.1021/jo015741c,2001-09-25,0.6224354464596569
Journal of the American Chemical Society,Cascade Polyketide and Polyene Cyclizations: Biomimetic Total Synthesis of Hongoquercin B,"The total synthesis of hongoquercin B was carried out in 9 steps from trans,trans-farnesyl acetate using a palladium catalyzed decarboxylative π-farnesyl rearrangement of a diketo-dioxinone ester, aromatization and cationic diene-epoxide cyclization as key steps. This cascade tetracyclization simplifies the synthesis of terpenoid resorcylate natural products.",10.1021/ja511534x,2014-11-25,0.622432246502746
European Journal of Organic Chemistry,Synthesis of Gabosine A and N from Ribose by the Use of Ring‐Closing Metathesis,"Abstract A concise synthetic route is described for the synthesis of gabosine A and N. The key step uses a zinc‐mediated tandem reaction where methyl 5‐deoxy‐5‐iodo‐2,3‐ O ‐isopropylidene‐β‐ D ‐ribofuranoside is fragmented to give an unsaturated aldehyde which is allylated in the same pot with 3‐benzoyloxy‐2‐methylallyl bromide. The functionalized octa‐1,7‐diene, thus obtained, is converted into the six‐membered gabosine skeleton by ring‐closing olefin metathesis. Subsequent protective group manipulations and oxidation gives rise to gabosine N in a total of 8 steps from ribose while the synthesis of gabosine A employs an additional step for inverting a secondary hydroxy group. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2009)",10.1002/ejoc.200800983,2008-12-04,0.6224278160206342
Journal of Organic Chemistry,"Synthesis of Monodisperse Oligo(1,4-phenyleneethynylene-alt-1,4-triptycyleneethynylene)s","The synthesis of monodisperse oligo(p-phenyleneethynylene)s 8a(n) with alternating 2,5-dihexyl-1,4-phenylene and 6,14-di-tert-butyl-1,4-triptycylene units and orthogonally protected alkyne end groups is reported. Starting from 6,14-di-tert-butyl-1-(2-triisopropylsilylethynyl)-4-(2-trimethylsilylethynyl)triptycene (5a), 1,4-dihexyl-2,5-diiodobenzene (10), and 1,4-dihexyl-2-iodo-5-(3-hydroxyprop-1-ynyl)benzene (9), oligomers with up to four repeating units, i.e., eight phenyleneethynylene units, were prepared through a partially divergent-convergent route with the alkynyl-aryl (Sonogashira-Hagihara) coupling as the key reaction. The starting compound 5a was prepared from triptycenequinone through a sequence of addition of 2-trialkylsilylethynyllithium, reduction and concomitant elimination of water, conversion of the phenol into a triflate, and finally Pd/Cu-catalyzed coupling with trialkylsilylethyne. A similar access to the key compound for a stringent divergent-convergent route, 6,14-di-tert-butyl-1-(3-hydroxybut-1-ynyl)-4-(2-triisopropylsilylethynyl)triptycene (6), is reported. The optical properties of the oligomers 8a(n) and the corresponding oligo(2,5-dihexyl-1,4-phenyleneethynylene)s in dilute solution are almost identical, whereas they differ significantly for the solid, undiluted compounds.",10.1021/jo9009744,2009-09-17,0.6224178768394216
Tetrahedron,Dithiocarbamates as an efficient intermediate for the synthesis of 2-(alkylsulfanyl)thiazoles in water,,10.1016/j.tetlet.2016.01.045,2016-01-16,0.6224164979813364
Synthesis,Regioselective Preparation of Functionalized Isoxazoline Derivatives as Key Intermediates for the Synthesis of Selective N-Methyl-d-aspartate Receptor Antagonists,"Two highly versatile isoxazoline derivatives, as key intermediates for the synthesis of differently functionalized subtype-selective N-methyl-d-aspartate receptor antagonists, were designed and synthesized. The synthetic strategy is based on an intramolecular nitrile oxide cycloaddition reaction which is a powerful method capable of controlling both the regio- and stereochemistry of the pericyclic reaction.",10.1055/s-0030-1258477,2011-03-16,0.6224107617527617
Tetrahedron,"Mechanism of the cyclopentane ring formation of allosamizoline, an aminocyclitol derivative of the chitinase inhibitor allosamidin",,10.1016/0040-4039(96)01207-5,1996-08-01,0.6224003705650287
Organic Process Research & Development,"Development of a Practical, Biocatalytic Synthesis of <i>tert</i>-Butyl (<i>R</i>)-3-Hydroxyl-5-hexenoate: A Key Intermediate to the Statin Side Chain","The HMG-CoA reductase inhibitors, statins, are one of the most effective and bestselling cholesterol-lowering drugs. The use of statins has greatly extended people’s lives and improved the quality of their life. Development of a more efficient, stereoselective, and sustainable synthesis of statins is continuingly of utmost importance. In the present study, through screening of ketoreductases (KREDs) and reaction optimization, we have successfully performed a highly stereoselective reduction of ketoester 1a catalyzed by KRED-06 at a pilot-plant scale without the addition of exogenous NADP +, generating 3.21 kg of enantiomerically pure tert -butyl ( R )-3-hydroxyl-5-hexenoate (( R )- 2a ) (96.2% yield, >99.9% enantiomeric excess (ee)). This newly developed biocatalytic process alleviates the cryogenic conditions (−40 °C) employed in our first-generation synthesis of ( R )- 2a using NaBH 4 and ( l )-tartaric acid. Coupled with our previously established synthesis of bromocarbonate 3a via a one-pot diastereoselective carboxylation/bromocyclization of ( R )- 2a, we have developed an innovative, practical synthesis route to statin side chain, possessing great potential to be implemented into industrial production of statins.",10.1021/acs.oprd.0c00320,2020-08-21,0.6223953731489992
Tetrahedron,An expeditious and convergent synthesis of ailanthoidol,,10.1016/j.tetlet.2010.02.018,2010-02-09,0.6223905462772326
Tetrahedron,A convergent synthesis of indoloquinones,,10.1016/s0040-4039(01)91504-7,1978-01-01,0.6223905462772326
Tetrahedron,Carbenoid insertion into alkenylzirconocenes—a convergent synthesis of functionalised allylmetallics,,10.1016/s0040-4039(00)01024-8,2000-08-01,0.6223905462772326
Tetrahedron,Convergent synthesis of diptoindonesin G,,10.1016/j.tetlet.2018.12.036,2018-12-17,0.6223905462772326
Tetrahedron,Convergent synthesis of (+)-muconin,,10.1016/s0040-4039(99)01629-9,1999-10-01,0.6223905462772326
Tetrahedron,Convergent synthesis of hexameric naphthylene macrocycles with dicarboxylic imide appendages,,10.1016/j.tetlet.2013.07.025,2013-07-11,0.6223905462772326
Synlett,Synthesis of 1-Azaspiroundecane Ring System via Thorpe-Ziegler Annulation of 2-Cyano-2-(4-Cyano-Tethered) Arylpiperidines,"An efficient stereocontrolled route to the 1-azaspiro[5.5]undecan framework of the histrionicotoxin alkaloids, employing anodic cyanation and Thorpe-Ziegler cyclization as key steps, is described. In the process of gaining information concerning the hydrolysis of the cyanoenamine function in 8, an unexpected intramolecular Friedel-Crafts type reaction provided the aza-fluorene 10.",10.1055/s-2002-31904,2002-01-01,0.6223801151758556
Journal of the American Chemical Society,The Total Synthesis of Tubulysin D,"The first total synthesis of tubulysin D is reported. The development and application of new tert-butanesulfinamide methods allowed for rapid syntheses of the tubuvaline and tubuphenylalanine fragments. Most significantly, a route was devised and implemented to introduce and carry forward the highly labile N,O-acetal functionality. Tubulysin D is the most active member of the tubulysin family, and the efficient synthetic route described herein will allow for the rapid syntheses of analogues to probe the biological activity of this important class of natural products.",10.1021/ja067177z,2006-12-01,0.6223797134395932
Organic Process Research & Development,One-Step Synthesis of 5-(4-Fluorobenzyl)-2-furyl Methyl Ketone: A Key Intermediate of HIV-Integrase Inhibitor S-1360,"Practical one-step synthesis of 5-(4-fluorobenzyl)-2-furyl methyl ketone was accomplished by Friedel–Crafts benzylation of 2-furyl methyl ketone with 4-fluorobenzyl chloride in the presence of ZnCl 2 . Two reaction conditions and their work-up procedures are reported. The first utilizes an anhydrous condition in dichloromethane, providing a convenient procedure for the isolation of the product. The second involves an aqueous condition, which offers a large-scale ecological and safe manufacturing process.",10.1021/op700117q,2007-10-10,0.6223786279059071
Journal of Organic Chemistry,Asymmetric Reductive Cyclization. Total Synthesis of (−)-C<sub>10</sub>-Desmethyl Arteannuin B,"An efficient total synthesis of (−)-C 10 -desmethyl arteannuin B ( 5 ) has been achieved. The sequence features the use of a chiral auxiliary to introduce absolute asymmetry at an early stage and a stereoselective, chelation-controlled reductive cyclization of 8, using samarium diiodide as the reducing agent. The methodology promises to be applicable to the synthesis of a wide range of analogs capable of being converted to potent antimalarial agents related to artemisinin ( 1 ).",10.1021/jo9600417,1996-01-01,0.622371280533172
Synlett,Diastereopure Synthesis of Novel Cyclohexane-Ring-Based Constrained Lanthionine and α-Methyllanthionine through an SN2 Reaction with a β-Bromoalanine as a Key Step,"Here we report the diastereopure synthesis of a novel protected lanthionine derivative substituted with a cyclohexane ring as well as the diastereopure synthesis of an α-methyllanthionine derivative. By starting from enantiopure α,β-cyclohexane-substituted cystine, or α-methylcysteine, we designed a straightforward route that permits the preparation of orthogonally protected modified lanthionines in diastereopure form. The key step of the methodology is the formation of a thioether bond through the use of an β-bromoalanine derivative. The strategy developed should be valuable in the preparation of a wide range of modified constrained lanthionines that might be finally attached to a peptide sequence, which would be especially useful in the syntheses of novel lantibiotics.",10.1055/s-0039-1690790,2020-01-13,0.6223703553834046
Journal of Organic Chemistry,Synthesis of Chiral <i>cis</i>-Cyclopropane Bearing Indole and Chromone as Potential TNFα Inhibitors,"Conformationally restricted analogues of SPD-304, the first small-molecule TNFα inhibitor, in which two heteroaryl groups, indole and chromone, are connected by chiral methyl- or ethyl- cis-cyclopropane, were designed. Synthesis of these molecules was achieved via Suzuki-Miyaura or Stille coupling reactions with chiral bromomethylenecyclopropane or iodovinyl- cis-cyclopropane as the substrate, both of which were prepared from chiral methylenecyclopropane as a common intermediate, constructing the heteroaryl-methyl or -ethyl- cis-cyclopropane structures as key steps. This study presents an efficient synthesis of a series of chiral cis-cyclopropane conjugates with two heteroaryl groups.",10.1021/acs.joc.8b00466,2018-07-13,0.6223620462518841
Organic Letters,Synthetic Studies on (+)-Ophiobolin A:  Asymmetric Synthesis of the Spirocyclic CD-Ring Moiety,"[reaction; see text] Asymmetric synthesis of the spirocyclic CD-ring moiety of (+)-ophiobolin A is described. Fragment A, which was prepared via pig liver esterase (PLE)-mediated kinetic resolution, and fragment B, which was prepared via diastereoselective allylation and subsequent kinetic iodolactonization, were coupled to afford the allylsilane 2, which was successfully cyclized to the desired spirocyclic CD-ring moiety 1a in the presence of a Lewis acid.",10.1021/ol060437x,2006-04-13,0.6223338486889438
Organic Process Research & Development,"An Efficient, Commercially Viable, and Safe Process for Preparation of Losartan Potassium, an Angiotensin II Receptor Antagonist","An efficient, commercially viable and safe process for the preparation of losartan potassium, an antihypertensive drug substance, with an overall yield of 55.5% and ∼99.9% purity (including five chemical reactions and two recrystallizations) and meeting all other regulatory requirements is described. Formation and control of all the possible impurities are also described.",10.1021/op300179u,2012-10-15,0.62232339354726
Organic Letters,Synthesis of the Pentacyclic Skeleton of the Indole Alkaloid Arboflorine,"An effective synthesis of the pentacyclic core of the unusual Kopsia alkaloid arboflorine is reported. The success of the synthetic route rested on the use of a borylative C-H functionalization reaction, a convergent Suzuki cross-coupling to a C(2) halogenated indole, and an unprecedented transannular dehydrogenative C-N bond forming reaction.",10.1021/ol302535r,2012-09-28,0.6223228634812747
Journal of Organic Chemistry,Construction of a BCDE Core of Furanosteroids Enabled by Nickel-Promoted Reductive Cyclization,"We developed a new synthetic strategy for furanosteroids and constructed the BE ring system in one step by a Ni-catalyzed reductive cyclization cascade. The subsequent oxidative elaboration led to the efficient formation of a BCDE tetracyclic core embedded in these furanosteroids. Furthermore, a synthesis of the carbon skeleton of nodulisporiviridin C was achieved, as well, through this method.",10.1021/acs.joc.5c01840,2025-10-03,0.6223130880039557
Organic Process Research & Development,"A Stereospecific Synthesis of 24(<i>S</i>)-Hydroxyvitamin D<sub>2</sub>, a Prodrug for 1α,24(<i>S</i>)-Dihydroxyvitamin D<sub>2</sub>","This contribution describes the first stereospecific synthesis of 24( S )-hydroxyvitamin D 2 ( 1 ), a metabolite of vitamin D 2 . This metabolite acts as a prodrug for 1α,24( S )-dihydroxyvitamin D 2 ( 2 ), which is under development for treatment of various diseases characterized by cellular hyperproliferation. The key step of the synthesis involves the Wittig−Horner olefination of ( S )-2,3-dimethyl-2-triethysilyloxybutyraldehyde ( 17 ) and a vitamin D 2 phosphine oxide derivative ( 22 ). The synthesis of the requisite aldehyde started with the commercially available l -(+)-valine and was completed in seven steps. The vitamin D 2 phosphine oxide derivative was synthesized in seven steps starting from vitamin D 2 .",10.1021/op010229e,2002-04-04,0.6222968861622389
Organic Process Research & Development,"Pilot-Plant Preparation of 3,4-Dihydropyridin-2-one Derivatives, the Core Structures of P2X<sub>7</sub>Receptor Antagonists","The pilot-plant syntheses of 3 and 4, the core structures of a series of P2X 7 antagonists are described. The sole stereogenic center in the dihydropyridinone ring was generated by catalytic desymmetrization. Selective formylation, followed by a tandem imination/lactamization sequence, produced the 3,4-dihydropyridin-2-one ring. The compounds 3 and 4 were produced at multikilogram scale in good overall yield (∼22% over six steps) and excellent stereochemical purity (97% ee for 3, 100% ee for 4) .",10.1021/op1000447,2010-04-02,0.622277814520509
Green Chemistry,Development of a bio-chemical route to C5 plasticizer synthesis using glutaric acid produced by metabolically engineered <i>Corynebacterium glutamicum</i>,An all-inclusive bio-chemical route from the fermentation process to downstream process for C5 plasticizer synthesis was developed using fermentation-derived glutaric acid produced by metabolically engineered Corynebacterium glutamicum .,10.1039/d1gc02686k,2022-01-01,0.6222661152856157
Organic Letters,Synthesis of α-S-Glycosphingolipids Based on Uronic Acids,The synthesis of S-glycosphingolipids based on uronic acids is described. These compounds are analogous to the highly immunostimulatory antigens isolated from the cell walls of bacteria of the Sphingomonas family. Key to the synthetic route is a stereoselective anomerization to give α-glycosyl thiol precursors. A route to a sphinganine precursor from pseudoephedrine glycinamide is also described.,10.1021/ol202042h,2011-08-29,0.6222650616656275
Journal of Organic Chemistry,Total Syntheses of All Stereoisomers of Phenatic Acid B,"The total syntheses of all stereoisomers of phenatic acid B and determination of their absolute configuration are described. The synthetic strategy is based on an efficient combination of the Sharpless asymmetric dihydroxylation, the Johnson-Claisen rearrangement, and hydroboration-oxidation. It involves 11-12 steps and overall yield of 5-8%.",10.1021/jo901927w,2009-10-28,0.6222451029276397
European Journal of Organic Chemistry,Enantioselective Modular Total Synthesis of Macrolides Sch725674 and C‐4‐<i>epi</i>‐Sch725674,"Abstract The convergent total synthesis of Sch725674 has been accomplished by starting from ( R )‐1,2‐epoxyheptane and assembling five modules in a highly stereoselective manner to give the final product in 6.6 % overall yield. The same strategy was extended to the synthesis of its C‐4 epimer. Key reactions of the synthetic pathway include a Jacobsen hydrolytic kinetic resolution of an epoxide followed by its regioselective opening through a Yamaguchi–Hirao alkynylation, and ring‐closing metathesis reaction to furnish the unique 14‐membered ring macrolactone. In addition, the influence of protecting groups on the efficiency of the ring‐closing metathesis (RCM) macrocyclization has been studied to maximize its yields.",10.1002/ejoc.201501531,2016-02-01,0.622243014996437
Organic Letters,Ag-Catalyzed Diastereo- and Enantioselective Synthesis of β-Substituted Tryptophans from Sulfonylindoles,"The asymmetric catalytic synthesis of beta-substituted tryptophan derivatives was realized in high diastereo- and enantioselectivity by the reaction of glycine derivatives with sulfonylindoles in the presence of catalyst derived from AgCl and a commercially available chiral monodentate phosphoramidite ligand. The resulting adduct was readily converted to beta-substituted tryptophan in 95% overall yield for two steps, which presented a highly efficient route to chiral beta-substituted tryptophan.",10.1021/ol100161n,2010-03-24,0.6222102651065666
Journal of the American Chemical Society,Highly Enantio- and Diastereoselective Tandem Generation of Cyclopropyl Alcohols with up to Four Contiguous Stereocenters,"Three highly enantio- and diastereoselective one-pot procedures for the synthesis of cyclopropyl and iodocyclopropyl alcohols with up to four contiguous stereocenters are reported. Route 1 involves asymmetric addition of an alkylzinc reagent to an enal followed by diastereoselective cyclopropanation. Route 2 parallels route 1, except that iodoform is used to generate the zinc carbenoid, and the products are iodocyclopropyl alcohols. Route 3 entails asymmetric vinylation of an aldehyde with divinylzinc reagents and subsequent diastereoselective cyclopropanation.",10.1021/ja0539239,2005-09-02,0.6222034918532281
Organic Letters,Asymmetric Synthesis of the Tetracyclic Core of Venezuelaene B,"A concise and efficient approach for the asymmetric synthesis of the tetracyclic core of venezuelaene B is described. Its uncommon and synthetically challenging [5-5-6-7] tetracyclic skeleton was constructed via a mild acid-promoted type I [5+2] cycloaddition, followed by a diastereoselective intramolecular Pauson-Khand reaction. The described chemistry establishes the feasibility of constructing the [5-5-6-7] tetracyclic core and several desired stereocenters (C2, C10, C11, and C14) of the final product.",10.1021/acs.orglett.5c00301,2025-04-01,0.6221963997888631
Synthesis,"A Convenient Synthesis of Isothiazolo[5,4-<i>b</i>]indole (Brassilexin) via a Polyphosphoric Acid Initiated Ring Closure","All articles of this category Brassilexin ( 4 ), an antifungal compound previously isolated from Brassica juncea L . (Cruciferae), has been synthesized with an overall yield of 11% starting from 3-indolecarbaldehyde ( 1 ).",10.1055/s-1990-26834,1990-01-01,0.6221941144915947
Angewandte Chemie International Edition,A Visible‐Light‐Mediated Radical Smiles Rearrangement and its Application to the Synthesis of a Difluoro‐Substituted Spirocyclic ORL‐1 Antagonist,"A visible-light-mediated radical Smiles rearrangement has been developed to address the challenging synthesis of the gem-difluoro group present in an opioid receptor-like 1 (ORL-1) antagonist that is currently in development for the treatment of depression and/or obesity. This method enables the direct and efficient introduction of the difluoroethanol motif into a range of aryl and heteroaryl systems, representing a new disconnection for the synthesis of this versatile moiety. When applied to the target compound, the photochemical step could be conducted on 15 g scale using industrially relevant [Ru(bpy)3Cl2] catalyst loadings of 0.01 mol %. This transformation is part of an overall five-step route to the antagonist that compares favorably to the current synthetic sequence and demonstrates, in this specific case, a clear strategic benefit of photocatalysis.",10.1002/anie.201507369,2015-10-16,0.622189253742895
Tetrahedron,Regiospecificity in the cyclization of 6-(1-hydroxyalkyl) geraniol derivatives. A simple route to the taxol a-ring system,,10.1016/s0040-4039(00)76737-2,1994-03-01,0.6221871773998447
Angewandte Chemie International Edition,Total Synthesis of an Atropisomer of the <i>Schisandra</i> Triterpenoid Schiglautone A,"A diastereoselective approach for the total synthesis of an unusual atropisomer of the Schisandra triterpenoid (±)-schiglautone A is described. The efficient synthetic strategy features three key transformations: 1) two sequential titanium(III)-catalyzed radical cyclization/homologation reactions to construct the trans-fused [6,7] bicycle as well as install the quaternary carbons at C10 and C14 with the desired stereochemistry; 2) a Claisen rearrangement followed by a ring-closing metathesis to forge the strained nine-membered ring; and 3) a substrate-controlled Michael addition to enable the introduction of the C17 side-chain with good diastereoselectivity.",10.1002/anie.201809076,2018-10-15,0.6221746898091208
Organic Process Research & Development,"Multikilogram Synthesis of a Potent Dual Bcl-2/Bcl-x<sub>L</sub> Antagonist. 2. Manufacture of the 1,3-Diamine Moiety and Improvement of the Final Coupling Reaction","This paper describes the synthesis of kilogram quantities of the sulfonamide moiety 3 involved in a coupling reaction with acid moiety 2 to provide batches of drug candidate 1 for preclinical studies and first-in-human clinical trials. A first approach relying on a chiral separation furnished the desired enantiomer of 1,3-diamine 20, precursor of sulfonamide 3 . An enantiomeric synthesis of 20 using the Ellman’s chiral auxiliary coupled with an aza-Reformatsky reaction to control the stereochemistry is also discussed. Coupling conditions of the final step involving EDCI to provide 1 under a cGMP process are detailed. An alternative approach using N -(1-methanesulfonyl)benzotriazole is also presented.",10.1021/acs.oprd.9b00367,2019-11-19,0.6221720783089475
Journal of the American Chemical Society,Total Synthesis of (−)-Tetrazomine. Determination of the Stereochemistry of Tetrazomine and the Synthesis and Biological Activity of Tetrazomine Analogues,"The first total synthesis of the potent antitumor antibiotic (-)-tetrazomine has been accomplished. A new method for the formation of the allylic amine precursor to an azomethine ylide has been developed and exploited in an efficient [1,3]-dipolar cycloaddition to afford the key tetracyclic intermediate used in the synthesis of (-)-tetrazomine. Several analogues of tetrazomine have been synthesized and tested for antimicrobial and biochemical activity.",10.1021/ja0174027,2002-02-22,0.6221581060225495
Tetrahedron,"Triphenyl verdazyl radicals’ reactivity with alkyne carboxylates as a synthetic route to 1-(phenyldiazenyl)isoquinoline-3,4-dicarboxylates",,10.1016/j.tetlet.2012.05.135,2012-06-07,0.6221485107926679
Synthesis,A New Efficient Synthesis of the Immunosuppressive Agent FTY-720,All articles of this category A new efficient five-step synthesis of the immunosuppressive agent FTY-720 is described. FTY-720 - immunosuppressive agent - acylations - reductions,10.1055/s-2000-6365,2000-01-01,0.622124714950015
Organic Letters,Oligocyclopropane Structural Units from Cationic Intermediates,syn - and anti- bis-cyclopropanes have been efficiently prepared through two distinct routes via the trapping of cyclopropylcarbinyl cationic intermediates. A ring-closing olefin metathesis for the formation of the necessary allylsilane precursors highlights the initial route. The cyclopropanation step proceeds in good yield to provide exclusively trans -vinylcyclopropanes. Iteration of the sequence has provided an efficient route to bis - cyclopropanes. The stereospecificity of the second cyclization was shown to be dependent on distal functionality. An alternative approach produces these interesting structural units from skipped dienes in a single step.,10.1021/ol990221d,1999-09-18,0.6221213730676882
Journal of Organic Chemistry,Synthetic Approaches to the Microtubule-Stabilizing Sponge Alkaloid Ceratamine A and Desbromo Analogues,"Two synthetic approaches to the microtubule-stabilizing ceratamine alkaloids are described. The first approach involved attempts to graft an aminoimidazole moiety onto an azepine ring to form partially hydrogenated versions of the unprecedented aromatic imidazo[4,5-d]azepine core of the ceratamines. This route ultimately failed because it was not possible to aromatize the partially hydrogenated ceratamine intermediates. A second approach started with tribromoimidazole that was sequentially metalated and functionalized to efficiently generate a key imidazole intermediate containing vinyl bromide and amide functionalities. An intramolecular Buchwald vinyl amidation reaction converted this key intermediate into a bicyclic imidazo[4,5-d]azepine that was at the same oxidation state as the aromatic core of the ceratamines. The 2-amino functionality present on the imidazole ring of the ceratamines was installed using a Buchwald/Hartwig amination reaction on a 2-chloroimidazole precursor. Deprotection and aromatization resulted in the first synthesis of desbromoceratamine A (55) and desmethyldesbromoceratamine A (60). An unanticipated addition of atmospheric oxygen was encountered during deprotection of the imidazole ring in the last step of the synthesis leading to C-11 oxygenated ceratamine analogues as byproducts. Evaluation of the synthetic ceratamines in a TG3 cell-based assay for mitotic arrest revealed that the C-14 and C-16 bromine substituents in ceratamine A (1) play a major role in the antimitotic potency of the natural product. The synthetic route to ceratamine analogues has provided sufficient quantities of desbromoceratamine A (55) for testing in mouse models of cancer.",10.1021/jo802322s,2009-01-07,0.622110379128827
Angewandte Chemie International Edition,Expedient Synthesis of (+)‐Lycopalhine A,"Two amino acids play a key role in the first total synthesis of lycopalhine A. L-glutamic acid serves as a convenient chiral starting material for the 13-step synthesis, and l-proline promotes an unusual 5-endo-trig Mannich cyclization that generates the central pyrrolidine ring of the Lycopodium alkaloid. The bicyclo[3.3.0]octanol moiety of the molecule is formed through an intramolecular aldol addition that may occur spontaneously in nature.",10.1002/anie.201509602,2016-01-08,0.6221049016504493
Journal of Organic Chemistry,Multicomponent Strategy for the Synthesis of Prostaglandin E<sub>2</sub> Methyl Ester under Anion Relay Chelation Control,"Starting with four components, the enantioselective synthesis of prostaglandin E2 methyl ester has been achieved through a highly stereoselective heteroatom-directed conjugate addition reaction and cyclopentanone ring cyclization as the key steps. This asymmetric strategy includes (i) an asymmetric Reformatsky reaction; (ii) conjugate addition of a chiral vinyllithium reagent; (iii) cyclization to form a sulfonylated cyclopentanone in one-pot; followed by (iv) allylation of the side chain. Four carbon-carbon bond-forming processes and three stereogenic centers were established, with the steps from (ii) to (iii) being achieved in a one-pot process.",10.1021/acs.joc.5b02735,2016-01-26,0.6220893408467053
Organic Letters,"Total Synthesis of Gymnorrhizol, an Unprecedented 15-Membered Macrocyclic Polydisulfide from the Chinese Mangrove <i>Bruguiera gymnorrhiza</i>","[reaction: see text] The total synthesis of gymnorrhizol, a naturally occurring macrocyclic polydisulfide with a new skeleton and a potent proteintyrosinephosphatase 1B inhibitor, was prepared in three steps, starting from (R)-1-bromo-3-chloroisopropanol and 1,3-dichloropropan-2-ol.",10.1021/ol0703783,2007-04-01,0.6220875735785037
Synlett,Synthetic Studies on a Nonsteroidal Progesterone Metabolite: Regioselective N-Alkylation of an Activated Pyrazole,This paper describes the large-scale synthesis of a progesterone receptor metabolite. The key step in this sequence was the regioselective pyrazole N-alkylation.,10.1055/s-0029-1219535,2010-02-23,0.6220845302384277
Synthesis,"A Practical Synthesis of the Kappa Opioid Receptor Selective Agonist (+)-5<b><i>R</i></b>,7<b><i>S</i></b>,8<b><i>S</i></b>-<b><i>N</i></b>-Methyl-<b><i>N</i></b>-[7-(1-pyrrolidinyl)-1-oxospiro[4,5]dec-8-yl]benzeneacetamide (U69,593)","A novel approach to the synthesis of the kappa opioid receptor agonist U69,593 has been developed. This approach improves upon current literature methods by substituting stable and isolable cyclic sulfates for the unstable epoxides. The new approach provides access to gram quantities of the target compound and displays excellent control of the relative stereochemistry. The absolute stereochemistry as well as biological activity of the U69,593 produced by this new method was verified using X-ray crystal structure analysis and binding assays for the kappa opioid receptor.",10.1055/s-2008-1032185,2008-03-01,0.6220681546246729
Synlett,Protecting-Group-Free Total Synthesis of Goniothalesdiol A,"A concise asymmetric total synthesis of goniothalesdiol A was accomplished using protecting-group-free strategy, in which silyl-Prins cyclization was used as the key step.",10.1055/s-0030-1258016,2010-08-06,0.6220606902258837
Angewandte Chemie International Edition,Total Synthesis of (+)‐Leucascandrolide A,"A convergent and enantioselective total synthesis of (+)-leucascandrolide (1) was accomplished in 17 steps. Central to this synthesis is the rapid and efficient integration of the bispyran moiety into 1 using two consecutive [4+2] annulation reactions between an aldehyde and the chiral silanes 2 and 3 (TMS=trimethylsilyl, Mes=mesityl=2,4,6-trimethylphenyl).",10.1002/anie.200462408,2005-01-17,0.622036219244738
Tetrahedron,"A short and efficient synthesis of the NMDA glycine site antagonist: (3R,4R)-3-amino-1-hydroxy-4-methyl pyrrolidin-2-one (L-687,414)",,10.1016/j.tetlet.2008.07.172,2008-08-07,0.6220300479944945
Organic Letters,A Concise Synthetic Approach to the Sorbicillactones: Total Synthesis of Sorbicillactone A and 9-<i>epi</i>-Sorbicillactone A,"A concise (12 step) total synthesis of sorbicillactone A and 9-epi-sorbicillactone A is reported. Unlike typical routes to the sorbicillinoids, this strategy does not start from sorbicillin and allows for the production of the bicyclic core on a multigram scale. The intramolecular conjugate addition of a tethered malonate serves as an effective means of introducing the lactone ring and provides a synthetic handle for installing the amide nitrogen.",10.1021/ol201211f,2011-07-29,0.6220285638914895
Tetrahedron,"An efficient one-pot, three-component route to novel push–pull 1,3-benzodithiol-2-ylidenes via copper-catalyzed bis-C S bond formation",,10.1016/j.tetlet.2022.153951,2022-06-24,0.6220236962908854
Journal of Organic Chemistry,Asymmetric Synthesis. 39.<sup>1</sup> Synthesis of 2-(1-Aminoalkyl)piperidines <i>via</i> 2-Cyano-6-phenyl Oxazolopiperidine,"The asymmetric synthesis of a series of 2-(1-aminoalkyl) piperidines using (-)-2-cyano-6-phenyloxazolopiperidine 1 is described. LiAlH(4) reduction of 1 followed by hydrogenolysis led to the diamine 3. The same strategy applied to C-2-methylated compound 7 afforded [(2S)-2-methylpiperidin-2-yl]methanamine (9). Addition of lithium derivatives to the cyano group of 1 resulted in the formation of an intermediate imino bicyclic system (11a-c) which could be diastereoselectively reduced to substituted diamino alcohols 13a-c. The addition of an excess of PhLi to 1 in the presence of LiBr furnished disubstituted amine 19, the precursor of diphenyl[(2S)-piperidin-2-yl]methanamine (22).",10.1021/jo960910s,1996-01-01,0.6220119263402273
Tetrahedron,Studies in marine macrolide synthesis: Asymmetric synthesis of C1-C15/C16 subunits of swinholide A and scytophycin C.,,10.1016/s0040-4039(00)73995-5,1993-08-01,0.6220075710400259
Journal of Organic Chemistry,"A Fast Assembly of Pentacyclic Benz[<i>f</i>]indolo[2,3-<i>a</i>]quinolizidine Core by Tandem Intermolecular Formal Aza-[3 + 3] Cycloaddition/Pictet−Spengler Cyclization:  A Formal Synthesis of (±)-Tangutorine","We have described a concise construction of the pentacyclic benz[f]indolo[2,3-a]quinolizidine intermediate 3 (with an overall yield of 54% for three steps), featuring a tandem intermolecular formal aza-[3 + 3] cycloaddition/Pictet-Spengler cyclization. The present work can be considered as a formal synthesis of beta-carboline alkaloid (+/-)-tangutorine. Our strategy disclosed herein constitutes a new effective general synthetic approach toward the indoloquinolizidine family of alkaloids.",10.1021/jo049459s,2004-05-20,0.6219930460806635
Journal of the American Chemical Society,Total Synthesis of the Diterpenes (+)-Randainin D and (+)-Barekoxide via Photoredox-Catalyzed Deoxygenative Allylation,"High Resolution Image Download MS PowerPoint Slide We report the first enantioselective total synthesis of diterpenoid randainin D, which possesses a hydroazulenone core with a β-substituted butenolide moiety on the cycloheptane ring. The trans -5/7 ring system was formed via a highly challenging ring-closing metathesis delivering the tetrasubstituted cycloheptenone. The butenolide moiety was installed via a novel deoxygenative allylation under Ir-photoredox catalysis, employing methyl oxalate as a red/ox tag. Moreover, the developed allylation was successfully utilized in the 7-step total synthesis of (+)-barekoxide. This study suggests that this deoxygenative allylation method is a promising strategy for the formation of Cq–C(sp 3 ) bonds (Cq = quaternary center) in the context of natural product synthesis.",10.1021/jacs.4c02224,2024-04-15,0.6219902207841521
Synthesis,Concise Total Synthesis of Complanadine A Enabled by Pyrrole-to-Pyridine Molecular Editing,"Abstract The Lycopodium alkaloid complanadine A, isolated in 2000, is a complex and unsymmetrical dimer of lycodine. Biologically, it is a novel and promising lead compound for the development of new treatments for neurodegenerative disorders and persistent pain management. Herein, we report a concise synthesis of complanadine A using a pyrrole-to-pyridine molecular editing strategy. The use of a nucleophilic pyrrole as the precursor of the desired pyridine enabled an efficient and one-pot construction of the tetracyclic core skeleton of complanadine A and lycodine. The pyrrole group was converted into a 3-chloropyridine via Ciamician–Dennstedt one-carbon ring expansion. A subsequent C–H arylation between the 3-chloropyridine and a pyridine N-oxide formed the unsymmetrical dimer, which was then advanced to complanadine A. Overall, from a readily available known compound, the total synthesis of complanadine A was achieved in 11 steps. The pyrrole-to-pyridine molecular editing strategy enabled us to significantly enhance the overall synthetic efficiency. Additionally, as demonstrated by Suzuki–Miyaura cross-coupling, the 3-chloropyridine product from the Ciamician–Dennstedt rearrangement is amenable for further derivatization, offering an opportunity for simplified analogue synthesis.",10.1055/a-2107-5159,2023-06-07,0.6219897017203404
European Journal of Organic Chemistry,"Synthesis of (23R)- and (23S)-23H-Isocalysterols, Marine Sterols with a Cyclopropene Moiety in the Side Chain","A synthesis of (23R)- and (23S)-23H-calysterols 2a and 2b from pregnanoic ester 10 is reported. Alkylation of 10 with dibromide 19b, followed by reduction of the carboethyloxy group to a methyl group, afforded (Z)-vinylic bromide 22. Dibromocyclopropanation of 22 yielded the diastereomeric tribromocyclopropane derivatives 15c and 15d. The corresponding 3-hydroxy-5-ene 17c was transformed into 2a via 25 and a cyclopropenyllithium intermediate. An alternative synthetic route involving vinylsilane 13 and (E)-vinylic bromide 14 has also been examined.",10.1002/(sici)1099-0690(200003)2000:6<1027::aid-ejoc1027>3.3.co;2-5,2000-03-01,0.6219786235804255
European Journal of Organic Chemistry,"Synthesis of (23R)- and (23S)-23H-Isocalysterols, Marine Sterols with a Cyclopropene Moiety in the Side Chain","A synthesis of (23R)- and (23S)-23H-calysterols 2a and 2b from pregnanoic ester 10 is reported. Alkylation of 10 with dibromide 19b, followed by reduction of the carboethyloxy group to a methyl group, afforded (Z)-vinylic bromide 22. Dibromocyclopropanation of 22 yielded the diastereomeric tribromocyclopropane derivatives 15c and 15d. The corresponding 3-hydroxy-5-ene 17c was transformed into 2a via 25 and a cyclopropenyllithium intermediate. An alternative synthetic route involving vinylsilane 13 and (E)-vinylic bromide 14 has also been examined.",10.1002/(sici)1099-0690(200003)2000:6<1027::aid-ejoc1027>3.0.co;2-e,2000-03-01,0.6219786235804255
Synthesis,"First Enantioselective Total Synthesis and Absolute Configurations of 4,5-Dioxo-seco-γ-eudesmol and 5β,11-Dihydroxyiphionan-4-one, Two Aglycones of Naturally Occurring Sesquiterpenes with New Skeletons","All articles of this category A facile synthetic route to two new carbon skeleton sesquiterpenes 4,5-dioxo-seco- γ -eudesmol and 5 β ,11-dihydroxyiphionan-4-one from (+)-dihydrocarvone has been described. The configuration of the 5 β ,11-dihydroxyiphionan-4-one was confirmed by stereospecific synthesis. enantioselective synthesis - sesquiterpenes - new carbon skeletons - 4,5-dioxo-seco- γ -eudesmol - 5 β ,11-dihydroxyiphionan-4-one",10.1055/s-2001-9742,2001-01-01,0.6219779795307954
Organic Process Research & Development,Preparation of the Key Intermediate in the Synthesis of GV143253A:  The Anti-MRSA/E Injectable Trinem,"GV143253A is a broad-spectrum injectable β-lactam belonging to the class of trinem antibiotics. A key intermediate (3 S,4 R )-3-[(1 R )-1-( tert -butyldimethyl- silyloxy)ethyl]-4-[-(6‘ R )-2‘-[( E )-(pyrid-4yl)methylene]-1‘-oxocyclohex-6‘-yl]azetidin-2-one (10) was identified and synthesized via different enolate coupling approaches, using enol ether, lithium, sodium, magnesium, tin, zinc, zirconium, and titanium enolates. Among these approaches, the synthesis of (3 S,4 R )-3-[(1 R )-1-( tert -butyldimethylsilyloxy)ethyl]-4-[-(6‘ R )-2‘-[( E )-(pyrid-4yl)-methylene]-1‘-oxocyclohex-6‘-yl]azetidin-2-one ( 10 ) via a titanium enolate offered advantages in terms of greater diastereoselectivity, higher yield, robustness, and isolation of intermediates and was superior to the method previously used for preparing large quantities of drug substance for early development studies.",10.1021/op020024l,2002-07-18,0.6219629446890476
Organic Letters,Bioinspired Stereoselective Total Synthesis of the Caged Sesquiterpenoid Daphnepapytone A,"The first total synthesis of the novel caged sesquiterpenoid daphnepapytone A is disclosed. Key reactions include a Pauson-Khand cycloaddition to provide oleodaphone, a bioinspired photoinduced [2 + 2] cycloaddition to forge the cyclobutane-containing caged skeleton, and a C-H oxidation and reduction protocol to generate daphnepapytone A. Finally, the 17-step synthetic sequence is shortened to 4 steps in protecting group-free and exclusively stereoselective fashion.",10.1021/acs.orglett.5c01509,2025-05-15,0.6219600659429579
Organic Letters,An Enantioselective Total Synthesis of (+)-Aigialospirol,"A concise and enantioselective total synthesis of (+)-aigialospirol is described here, featuring the first complex natural product synthesis that employs a cyclic ketal-tethered ring-closing metathesis strategy and an unexpected stereoselective epimerization of a benzylic hydroxyl group. The 15-step synthetic sequence illustrates the proof-of-concept that such an approach can be competitive with the classical spiroketal formation in the natural product synthesis.",10.1021/ol702195w,2007-10-20,0.6219496493862028
Journal of Organic Chemistry,"Stereoselective Synthesis of Furo[2,3-<i>c</i>]pyridine Pyrimidine Thioethers, A New Class of Potent HIV-1 Non-nucleoside Reverse Transcriptase Inhibitors","An efficient stereoselective total synthesis of the furo[2,3- c ]pyridine thiopyrimidine HIV-1 reverse transcriptase inhibitors, PNU-142721 and PNU-109886, has been developed. A convergent approach was utilized, providing direct access to the desired ( S )-configuration of the molecule by making use of the alkylation of 4-amino-6-chloro-2-thiopyrimidine with the appropriate ( R )-1-chloroethyl furo[2,3- c ]pyridine intermediates. The successful preparation makes use of an efficient enzymatic kinetic resolution of the key 1-hydroxyethyl furo[2,3- c ]pyridine intermediates to establish stereochemical control of the respective stereogenic centers. In addition, a workable asymmetric reduction strategy was developed for the synthesis of PNU-109886. Prudent reagent selection for the chlorination required for the final coupling reactions allowed for maintenance of the stereochemical integrity of the target compounds. Structural assignment of the absolute configuration of PNU-142721 and PNU-109886 as the ( S )-enantiomer was confirmed by X-ray crystallographic analysis.",10.1021/jo9810359,1998-10-01,0.6219432677069652
Synthesis,A Short Route to 2-(6-Methoxycarbonylhexyl)-cyclopent-2-en-1-one,"All articles of this category The prostaglandin intermediate 2-(6-methoxycarbonylhexyl)-cyclopent-2-en-1-one ( 5 ) has been prepared by a short synthetic sequence, consisting of the reaction of 2-(1,3-dioxolan-2-yl)-ethylmagnesium bromide ( 1 ) with methyl 9-chloro-9-oxononanoate ( 2 ), followed by cleavage of the dioxolane ring of 3 and base-induced cyclisation of 4 .",10.1055/s-1986-31618,1986-01-01,0.6219419794077534
Organic Letters,Progress toward the Total Synthesis of Gukulenin A: Photochemically Triggered Two-Carbon Ring Expansion Key to α-Tropolonic Ether Synthesis,"The ex-chiral-pool synthesis of an advanced gukulenin A precursor from (−)-piperitone is revealed. Key C/C connecting maneuvers to the synthesis of a C 2 dissymmetric bis(α-tropolonic) ether building block are a ring-contracting Meinwald rearrangement, a photochemically triggered two-carbon ring expansion, and a homodimerization by cross-metathesis.",10.1021/acs.orglett.8b01629,2018-06-19,0.6219392800068051
Tetrahedron,A novel approach to the asymmetric synthesis of manzamine A. Construction of the tetracyclic ABCE ring system,,10.1016/s0040-4039(00)75792-3,1994-01-01,0.6219318732524269
Journal of Organic Chemistry,Efforts toward the Total Synthesis of Elisabethin A,"We describe our efforts toward the total synthesis of the natural product elisabethin A. The first route was guided by the proposed biosynthesis, assembling the 6,6-ring system before forming the five-membered ring including the quaternary carbon. The second approach includes a high yielding cyclization under Mitsunobu conditions as a key step. It allowed the preparation of an unusual and highly functionalized bicyclic 6,5-spiro compound. Both routes share a common advanced precursor obtained from an ""underdeveloped"" Claisen rearrangement of an aryl dienyl ether.",10.1021/acs.joc.2c01914,2022-10-25,0.6219246048426034
Organic Letters,Total Synthesis of (±)-2-<i>O</i>-Methylneovibsanin H,"The total synthesis of (+/-)-2- O-methylneovibsanin H was achieved in 12 steps. An acid-catalyzed, one-pot, four-step cascade reaction was key to the concise total synthesis, lending support to the proposed biosynthesis.",10.1021/ol801117e,2008-07-12,0.6219233979469883
Journal of Organic Chemistry,A Novel Route to Fully Substituted 1<i>H</i>-Pyrazoles,"A novel one-step synthesis route to fully substituted pyrazol-4-ols is reported. This simple yet nonobvious method for the construction of pyrazol-4-ols by the condensation-fragmentation-cyclization-extrusion reactions of thietanones with 1,2,4,5-tetrazines is reported. All of the elements of the thietanone except its sulfur are incorporated in these novel products.",10.1021/jo051319a,2005-09-17,0.621919353593405
Organic Letters,"Rapid Assembly of the Polyhydroxylated β-Amino Acid Constituents of Microsclerodermins C, D, and E","A very short and efficient synthesis of protected derivatives of APTO and AETD, the complex polyhydroxylated beta-amino acid residues present in microsclerodermins C, D, and E, is described. The targets are obtained in only five steps, in 23% and 16% overall yields, respectively. The key transformation involves the completely diastereoselective two-carbon homologation of appropriately selected intermediate chiral sulfinimines.",10.1021/ol702962z,2008-02-07,0.6219145764993053
Journal of Organic Chemistry,Total Synthesis of (−)-Pavidolide B: A Ring Contraction Strategy,"A ring contraction approach for the total synthesis of (−)-pavidolide B was developed, which assembles this polycyclic natural product within 13 steps from known chiral alcohol 11 . The key features of the strategy include (a) a double Mukaiyama–Michael addition/elimination, (b) a ring-closing metathesis, (c) a Wolff rearrangement, and (d) a late-stage regioselective Schenck ene reaction.",10.1021/acs.joc.9b01308,2019-06-21,0.6219035497719154
Tetrahedron,"Regioselective 9- aryl radical cyclisation: A new synthetic route to decahydro-5-dibenzo[a,d] and [a,e]-cyclononenols",,10.1016/0040-4039(95)00880-l,1995-07-01,0.6218952473451735
Tetrahedron,"Regioselective 9-? Aryl Radical Cyclisation: A New Synthetic Route to Decahydro-5?-dibenzo[a,d] and [a,e]-Cyclononenols",,10.1016/00404-0399(50)0880l-,1995-07-03,0.6218952473451735
Journal of the American Chemical Society,"Remarkable Control of Radical Cyclization Processes of Cyclic Enyne:  Total Syntheses of (±)-Methyl Gummiferolate, (±)-Methyl 7<i>β</i>-Hydroxykaurenoate, and (±)-Methyl 7-Oxokaurenoate and Formal Synthesis of (±)-Gibberellin A<sub>12</sub> from a Common Synthetic Precursor","Total syntheses of (+/-)-methyl gummiferolate (13b), (+/-)-methyl 7beta-hydroxykaurenoate (14b), and (+/-)-methyl 7-oxokaurenoate (14d) and a formal synthesis of (+/-)-gibberellin A(12) (15) have been accomplished through the common synthetic precursor, (3aR,7aR)-3,3-dimethyl-7a-(2-propynyl)-3a,4,7,7a-tetrahydroisobenzofuranone (16). The homoallyl-homoallyl radical rearrangement reaction of the monocyclic enyne 25, derived from 16 in two steps, afforded the bicyclo[2.2.2]octane compound 26, which was converted to (+/-)-methyl gummiferolate (13b). In contrast, the radical cyclization of the bicyclic enyne 16 gave the tricyclic lactone 19, leading to (+/-)-methyl 7beta-hydroxykaurenoate (14b) and (+/-)-methyl 7-oxokaurenoate (14d). Transformation of 14d into lactone 20 was carried out in a single step under bromination conditions. This constitutes a formal total synthesis of gibberellin A(12) (15).",10.1021/ja0035506,2001-02-10,0.621893433748936
European Journal of Organic Chemistry,Synthetic Routes to Isomeric Imidazoindoles by Regioselective Ring‐Opening of Activated Aziridines Followed by Copper‐Catalysed C–N Cyclization,"Two new synthetic routes that deliver substituted imidazoindoles in high yields with excellent ee values have been developed. The reactions proceed through ring‐opening of activated aziridines with 2,2‐dibromovinylanilines or 2‐bromoindoles, followed by a Cu‐catalysed domino C–N,C–N‐cyclization, or a C–N cyclization, respectively. The first route gives rise to one regioisomer, and the second route gives the other.",10.1002/ejoc.201700267,2017-02-24,0.6218889399104219
Journal of the American Chemical Society,A Biomimetic Synthesis Elucidates the Origin of Preuisolactone A,"A short, biomimetic synthesis of the fungal metabolite preuisolactone A is described. Its key steps are a purpurogallin-type (5 + 2)-cycloaddition, followed by fragmentation, vinylogous aldol addition, oxidative lactonization, and a final benzilic acid rearrangement. Our work explains why preuisolactone A has been isolated as a racemate and suggests that the natural product is not a sesquiterpenoid but a phenolic polyketide.",10.1021/jacs.9b08892,2019-09-13,0.6218857108890183
Synthesis,"Efficient Synthesis of the Aonidiella aurantii (Mask.) Sex Pheromone Component: (3S,6RS)-3-Methyl-6-(1-Methylethenyl)-9-decenyl Acetate","All articles of this category The title compound, active component of the sex pheromone of Aonidiella aurantii (California Red Scale), was synthesized in three steps starting from S -citronellyl acetate with a 30% overall yield. The key feature of the synthesis is a copper salt assisted, highly regioselective attack of the 4-butenyl bromide Grignard reagent on the γ -site of the chloroallylic system of ( S )-8-chloro-3,7-dimethyl-6-octenyl acetate (8a) . regiospecific copper assisted Grignard C -alkylation of allylic chloride - pheromone synthesis",10.1055/s-1995-3966,1995-06-01,0.6218796652442049
Organic Process Research & Development,A Chemoenzymatic Synthesis of an Androgen Receptor Antagonist,"A new scalable enzymatic resolution approach to both enantiomers of trans -2-hydroxycyclohexanecarbonitrile ( 9 and 11 ) was developed. Treatment of the racemic mixture ( 4 ) with succinic anhydride in the presence of Novozym 435 led to selective acylation of one enantiomer to the corresponding hemisuccinate, which was separated from the unreacted enantiomer by a simple basic extraction. This procedure produced the desired enantiomer in high ee, while obviating the need for chromatography or expensive catalysts and ligands. The application of this protocol to the large-scale synthesis of an androgen receptor antagonist ( 1 ) is described.",10.1021/op700146c,2007-09-01,0.6218780288479758
Synlett,The First Total Synthesis of the Antimicrobial Sesquiterpenes (±)-Enokipodins A and B,"Efficient first total synthesis of antimicrobial sesquiterpenes enokipodins A and B (1 and 2, respectively) and formal total synthesis of cuparene-1,4-diol (5) and cuparene-1,4-quinone (7) have been accomplished starting from 2,5-dimethoxy-4-methyl­acetophenone employing Claisen rearrangement and ring-closing metathesis reaction as key steps.",10.1055/s-2003-45003,2004-01-01,0.6218772466979952
Organic Letters,Asymmetric Total Synthesis of (−)-Lycospidine A,"The first asymmetric total synthesis of the structurally unique Lycopodium alkaloid (-)-lycospidine A, containing an unprecedented five-membered ring, has been accomplished in only 10 steps with 21.6% overall yield from the known conveniently available sulfoxide. This protecting-group-free short synthesis relied on the use of a key amidation/aza-Prins domino cyclization reaction to rapidly construct the tricyclic skeleton and two continuous stereocenters (one of which is a bridged quaternary stereocenter). An intramolecular aldol condensation was successfully utilized to establish the unique five-membered ring, and a late-stage oxidation inspired by biosynthesis pathway was adopted to synthesize the diosphenol ring of (-)-lycospidine A.",10.1021/acs.orglett.6b02322,2016-08-26,0.6218645337886293
Tetrahedron,"Highly efficient synthesis of alka-1,3-dien-2-yltitanium compounds from alka-2,3-dienyl carbonates. A new, practical synthesis of 1,3-dienes and 2-iodo-1,3-dienes",,10.1016/s0040-4039(96)02126-0,1996-12-01,0.6218623685369299
Synlett,Towards the Total Synthesis of Schisandrene: Stereoselective Synthesis of the Dibenzocyclooctadiene Lignan Core,"A stereoselective synthesis of the dibenzocyclooctadiene ­lignan core of the natural product schisandrene is described. Starting from readily available gallic acid, the synthetic strategy involves Suzuki–Miyaura cross-coupling, Stille reaction, and ring-closing metathesis (RCM) in the reaction sequence. The required asymmetric center at C-7′ was established by an asymmetric reduction of a keto compound using the Corey–Bakshi–Shibata (CBS) catalyst. In our approach, the eight-membered ring was achieved by RCM for the first time.",10.1055/s-0036-1591539,2018-02-19,0.6218593254443604
Synlett,"Asymmetric Total Synthesis of Pseudoplexaurol and 14-Deoxycrassin, two Antitumor Marine Cembrane Diterpenoids",The first asymmetric total synthesis of two naturally occurring antitumor pseudoplexaurol and 14-deoxycrassin were achieved via two convergent synthetic sequences featured a chiral pool protocol to implement C-1 stereogenic center and Ti(0)-mediated cyclization leading to cembrane ring.,10.1055/s-2003-42077,2003-01-01,0.621855679084181
Tetrahedron,"2,4-Dinitrophenol: a novel activating reagent in nucleotide synthesis via the phosphoramidite route. Design of new effective phosphitylating reagents",,10.1016/s0040-4039(00)01178-3,2000-09-01,0.6218439176118001
Organic Letters,Total Synthesis of (±)-Lundurine B,"A total synthesis of (±)-lundurine B was accomplished. A combination of stereoselective intramolecular cyclopropane formation and aryl amination furnished cyclopropane-fused indoline stereoselectively. Ring-closing metathesis (RCM) of siloxy diene and intramolecular aminoacetal formation followed by bridgehead vinylation of an anti-Bredt iminium cation led to the construction of six- and seven-membered rings with a quaternary carbon center. After the formation of dihydropyrrole by RCM, the Boc-protecting group of indoline was converted into the corresponding methyl carbamate via silyl carbamate to complete the total synthesis of (±)-lundurine B. The characteristic rearrangement of the cyclopropane-fused indoline skeleton is also described.",10.1021/ol4034786,2014-01-15,0.6218403540899824
Journal of Organic Chemistry,Asymmetric Total Synthesis of Nannocystin A,"Nannocystin A is a novel 21-membered macrolactone isolated from myxobacterium Nanocystis sp. It is a potent elongation factor 1 inhibitor and inhibits cancer cell line growth at nanomolar concentrations. In this work, a concise asymmetric total synthesis of nannocystin A has been developed, which features Sharpless epoxidation, Stille coupling, and final macrolactamization.",10.1021/acs.joc.7b01502,2017-08-08,0.6218342533844007
Tetrahedron,"Asymmetric Synthesis of γ-Hydroxy α,β-Unsaturated Amides via an AD-elimination Process; Synthesis of (+)-Coriolic Acid",,10.1016/s0040-4039(00)60351-9,1993-03-01,0.6218165214543774
Organic Process Research & Development,An Improved Process for the Preparation of a Covalent Kinase Inhibitor through a C–N Bond-Forming S<sub>N</sub>Ar Reaction,"An improved API step for the formation of an aminopyrimidine-based kinase inhibitor is described. The presence of a reactive acrylamide functional group presented a considerable challenge during scale-up, resulting in side-product formation and low in-process yields for the final S N Ar reaction. Impurity identification guided process development efforts, enabling rapid scale-up of a safe and phase-appropriate process to deliver the API to support toxicology studies.",10.1021/acs.oprd.8b00080,2018-06-12,0.621813653067371
European Journal of Organic Chemistry,Asymmetric Total Synthesis of the Gastroprotective Microbial Agent AI‐77‐B,"Abstract An enantioselective total synthesis of the pseudopeptide microbial agent AI‐77‐B, which has shown potent antiulcerogenic properties, is described. The synthesis is convergent and involves the assembly of a dihydroisocoumarin fragment and a hydroxy amino acid. The dihydroisocoumarin derivative was synthesised by means of a Diels−Alder reaction between 1‐methoxy‐1,3‐cyclohexadiene and an alkynyl ester derivative as the dienophile. The alkynyl ester was obtained stereoselectively by two different synthetic routes: (1) A stereoselective allylation of leucinal, and (2) a titanium enolate‐mediated anti ‐aldol reaction with trichlorobutyraldehyde, a novel homopropargylaldehyde equivalent. The stereocentres of the hydroxy amino acid moiety were generated through a titanium enolate‐mediated syn ‐aldol reaction, Curtius rearrangement, and application of Dondoni's aldehyde homologation. Condensation of the dihydroisocoumarin and hydroxy amino acid moieties and subsequent removal of the protecting groups furnished optically active AI‐77‐B. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2003)",10.1002/ejoc.200390125,2003-02-10,0.6218099569169478
Organic Letters,Enantioselective Synthesis of the C8−C20 Segment of Curvicollide C,"The enantioselective synthesis of the C8-C20 fragment of curvicollide C has been accomplished. A catalytic asymmetric Claisen rearrangement (CAC), a diastereoselective methyl cupration of an alkynoate, and a Julia-Kocienski olefination served as key C/C-connecting transformations.",10.1021/ol702092h,2007-10-25,0.6218073353841975
Synthesis,Asymmetric Total Synthesis of Tylophorine through a Formal [2+2] Cycloaddition Followed by Migrative Ring Opening of a Cyclobutane,"The asymmetric total synthesis of phenanthroindolizidine alkaloid (–)-tylophorine was achieved by asymmetric transfer hydrogenation of a cyclic imine. The cyclic imine with a pendant phenanthrene core was synthesized by a TfOH-promoted domino ring-contraction/ring-opening sequence of a cyclobutanol bearing an azide group, which was constructed by a formal [2+2] cycloaddition of a 2′-vinyl-1,1′-biaryl-2-yl ketone enolate. Catalytic asymmetric hydrogenation of the cyclic imine intermediate allowed the late-stage construction of the asymmetric center.",10.1055/s-0034-1380430,2015-07-01,0.6217997559663747
Synlett,"Expedient Synthesis of 6-Acylindolo[1,2-a]quinoxalines","A novel route leading to 6-acylindolo[1,2- a ]quinoxalines ­involving condensation of N -(2-iodoaryl)-2-nitrosoanilines with β-di­ketones followed by Heck cyclization is described.",10.1055/s-0034-1380515,2015-04-10,0.6217955972051009
Tetrahedron,A novel enantioselective synthesis of (+)-biotin,,10.1016/s0040-4039(00)79354-3,1993-07-01,0.6217844061085227
Tetrahedron,A novel enantioselective synthesis of (+)-biotin,,10.1016/s0040-4039(00)77187-5,1994-04-01,0.6217844061085227
Journal of Organic Chemistry,Total Synthesis of a Thymidine 2-Deoxypolyoxin C Analogue,"The synthesis of the thymidine 2-deoxypolyoxin C analogue 10 from a noncarbohydrate precursor was achieved in 10 steps and 9% yield starting from a chiral gamma,delta-epoxy-beta-hydroxy ester 11 readily available from cis-2-butene-1,4-diol. The main steps concern the stereo- and regioselective opening of the epoxide ring by an azide anion, the stereoselective introduction of the thymine base, and the transformation of the primary alcohol to the acid functionality of the final product. Two other approaches have also been investigated.",10.1021/jo972116s,1998-03-28,0.6217821448674686
Journal of Organic Chemistry,Total Synthesis of Cruentaren B,"A convergent total synthesis of the cytotoxic natural product cruentaren B is completed in 26 steps (longest linear sequence) with an overall yield of 7.1%. For the construction of the C1-C11 benzolactone fragment of the molecule, the key steps used were O-methylation, using a Mitsunobu reaction, a Stille coupling method to construct the C7-C8 bond, and a Brown's asymmetric crotylboration reaction for the direct enantioselective installation of the two chiral centers present in this fragment. For diastereoselective installation of the chiral centers in the C12-C20 polyketide fragment, an Evans syn aldol reaction on a chiral aldehyde, derived from methyl (R)-3-hydroxyl-2-methylpropionate, and subsequently a Mukaiyama aldol reaction were employed. For the construction of the C21-C28 tail, a ""non-Evans"" syn aldol reaction was used. The three fragments were coupled by an SN2 reaction and a Wittig olefination reaction followed by standard functional group manipulations to furnish the target molecule.",10.1021/jo800181n,2008-03-26,0.6217806789271576
Journal of Organic Chemistry,"Formal Total Synthesis of (±)-Estrone and Zirconocene-Promoted Cyclization of 2-Fluoro-1,7-octadienes and Ru-Catalyzed Ring Closing Metathesis","A new and diastereoselective method for the synthesis of the estrone skeleton from a substituted styrene based on sequential 3-fold use of Cp 2ZrBu 2 (oxidative addition-alkylation and two cyclization-alkylation sequences) and a ruthenium complex catalyzed RC-metathesis of a sterically hindered diene was developed. The prepared estratetraene was obtained in 7 steps from a commercially available starting material and thus the overall synthesis of estrone could be accomplished in 9 steps. Moreover, we have also found that the course of the reaction of substrates bearing the 2-halo-1,7-diene moiety with Cp 2ZrBu 2, i.e., cyclization or oxidative addition to the C-X bond, could be controlled by the nature of the halogen leaving group.",10.1021/jo800620d,2008-07-16,0.6217753751044075
Synthesis,"A Convenient Method for the Preparation of 4-Hydroxy-2-methyl-1-oxo-1,2-dihydroisoquinoline-3-carboxylic Acid Derivatives","An improved method for the synthesis of 4-hydroxy-2-methyl-1-oxo-1,2-dihydroisoquinoline-3-carboxylic acid derivatives is described. The synthetic route involves initial phthalic anhydride aminolysis with alkylaminoacetic acid derivatives, further esterification with diazomethane and final heterocyclization of the phthalamic ester intermediates by alkoxide-induced Dieckmann condensation. The best yields are reached for esters and N,N-disubstituted carboxamides.",10.1055/s-2006-942402,2006-06-01,0.6217745542921969
Tetrahedron,Stereoselective synthesis of a synthon for the A-ring of taxol from R-(+)-verbenone,"The efficient conversion of R-(+)-verbenone to bicyclic lactone 6, a potentially useful intermediate for the synthesis of taxanes, is described. The introduction of C-1 (taxane numbering) oxygen functionality is also reported, thereby completing the synthesis of the A-ring subunit of taxol.",10.1016/0040-4039(95)00257-d,1995-03-01,0.6217697648114179
Journal of the American Chemical Society,Catalytic Asymmetric Synthesis of Either Enantiomer of the Calabar Alkaloids Physostigmine and Physovenine,"A potentially versatile asymmetric route to hexahydropyrrolo[2,3- b ]indoles having carbon substituents at C-3a (Scheme 1) is demonstrated through enantioselective total syntheses of the Calabar alkaloids (−)-physostigmine ( 2 ), (−)-physovenine ( 10 ), and their enantiomers. The synthesis of enantiopure (−)-physostigmine proceeds from commercially available 2-butyn-1-ol ( 11 ) and N -methyl- p -anisidine ( 15 ) in 15−20% overall yield by way of eight isolated and purified intermediates. The central step is catalytic asymmetric Heck cyclization of ( Z )-2-methyl-2-butenanilide 17 to form oxindole aldehyde ( S )- 19 in 84% yield and 95% ee.",10.1021/ja980788+,1998-06-20,0.6217693125965039
Journal of the American Chemical Society,Rapid Synthesis of Polyamide Dendrimers from Unprotected AB<sub>2</sub> Building Blocks,"A rapid synthetic method for the preparation of polyamide dendrimer without protection and deprotection steps has been developed. A symmetrically branched third-generation polyamide dendrimer was prepared by a convergent method involving activation of focal point with a condensing agent, diphenyl (2,3-dihydro-2-thioxo-3-benzoxazolyl)phosphonate (DBOP), followed by condensation of the active amide with the diaminocarboxylic acid 3,5-bis(4-aminophenoxy)benzoic acid as an AB2 building block.",10.1021/ja034665n,2003-06-14,0.6217637256971523
Journal of Organic Chemistry,A Synthetic Route to Functionalized Thiopyran Derivatives via Domino Ring-Opening Cyclization (DROC) of Donor–Acceptor Cyclopropanes with Pyridinium Thiolates,"An efficient route to 5,6-dihydro-4 H -thiopyran derivatives is developed via domino ring-opening cyclization (DROC) of activated donor–acceptor (DA)-cyclopropanes with pyridinium thiolates in the presence of Yb(OTf) 3 as the Lewis acid and K 2 CO 3 as the base under mild conditions in moderate to excellent yields. Enantiospecific S N 2-type DROC of nonracemic DA-cyclopropane (ee 97%) with pyridinium thiolate afforded the corresponding nonracemic thiopyran product with high yield and excellent enantiospecificity (>97%). This approach offers a straightforward and practical route to thiopyran frameworks of synthetic and biological significance.",10.1021/acs.joc.5c00292,2025-06-13,0.6217604107956862
Organic Process Research & Development,"Correction to “Development of an Optimized Process for 2,4-Dichloro-5-fluoroacetophenone: A Key Intermediate of Ciprofloxacin”",,10.1021/acs.oprd.4c00545,2025-01-15,0.621756717636098
European Journal of Organic Chemistry,"Diastereoselective Approaches to trans-Hydrindane Derivatives − Total Synthesis of 8-(Phenylsulfonyl)de-A,B-cholestane Precursors to 25-Hydroxyvitamin D3","The total diastereoselective synthesis of the C,D rings/side chain building block for the synthesis of 1α,25-dihydroxyvitamin D3 is described. Two tandem Mukaiyama−Michael additions involving silylated ketene acetals derived from tert-butyl 6-methylhept-5-enethioate or tert-butyl 6-methylhept-6-enethioate, 2-methylcyclopent-2-en-1-one, and 1-(phenylthio)but-3-en-2-one afforded the corresponding intermediates with the complete carbon framework of the target compound. The further transformation of these key intermediates involved cyclization, oxidation with m-CPBA, and reduction of the vinylic sulfone moiety to afford the trans-hydrindane ring system. The synthesis comprises five operations and afforded the product in ca. 30% yield. The application of 2-[(phenylthio)methyl]-2-vinyl[1,3]dioxolane and 2-(phenylsulfonylmethyl)-2-vinyl[1,3]dioxolane as Michael acceptors was also examined. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)",10.1002/1099-0690(200208)2002:16<2727::aid-ejoc2727>3.0.co;2-1,2002-08-01,0.6217533510122104
Journal of Organic Chemistry,"Chemical Synthesis of β-Homonojirimycin, of Its <i>N</i>-Butyl Derivative, and of “Methyl Homoazacellobioside”","beta-Homonojirimycin (2) was prepared by the highly stereoselective double reductive amination of a 2,6-heptodiulose derivative (6 or 13) using ammonium formate and NaBH(3)CN. The process was unsuccessful with primary amines. The synthesis of N-butyl-beta-homonojirimycin (19) was achieved by the N-butanoylation of a derivative of 2 followed by the reduction of the resulting tertiary amide. Compound 19 was found to be completely devoid of anti-HIV activity, in marked contrast with N-butyl-1-deoxynojirimycin. The coupling of the 1-O-p-toluenesulfonyl derivative of 2, compound 20, with methyl 2,3,6-tri-O-benzyl-alpha-D-glucopyranoside, followed by a deprotection step, provided pseudodisaccharide 23, the ""homoaza"" analog of methyl alpha-cellobioside and a potential inhibitor of beta-glucan-processing enzymes.",10.1021/jo960362i,1996-01-01,0.6217400757687787
Synlett,Synthetic Studies toward the Total Synthesis of Chlorahololide A,"The highly stereoselective synthesis of core framework 4, a pivotal intermediate for the total synthesis of chlorahololide A, is reported. The approach features t-BuCu-mediated stereoselective reduction of α,β-unsaturated diketone 8, Wharton transposition, Simmons-Smith cyclopropanation and cascade enol lactonization.",10.1055/s-0030-1259677,2011-02-22,0.6217380380628743
Journal of the American Chemical Society,Asymmetric Total Synthesis of (+)-Alstonlarsine A,"The first asymmetric total synthesis of (+)-alstonlarsine A has been realized. The prominent features of the current synthesis include the following: (i) a Pd/self-adaptable ligand complex-catalyzed asymmetric allylic alkylation of 2-methyl-2-cyclopentenyl carbonate with 2-indolylsubstituted dimethyl malonate to establish the key stereocenter of C15, (ii) an intramolecular nitrile oxide-alkene [3 + 2] cycloaddition (INOC [3 + 2]) to construct the cyclohepta[ b ]indole backbone with the installment of the requisite stereochemistry of the all-carbon quaternary center of C20, and (iii) a late-stage interrupted Pictet–Spengler reaction (IPSR) to rapidly assemble the core structure of (+)-alstonlarsine A.",10.1021/jacs.2c06518,2022-07-27,0.6217378348627209
Journal of Organic Chemistry,"Enantioselective Synthesis of 7(<i>S</i>)-Hydroxydocosahexaenoic Acid, a Possible Endogenous Ligand for PPARα",We report the first total synthesis of the polyunsaturated fatty acid 7-hydroxydocosahexaenoic acid (7-HDHA) in racemic form and the enantioselective synthesis of 7-( S )-HDHA. Both syntheses follow a convergent approach that unites the C1–C9 and C10–C22 fragments using Sonogashira coupling and Boland reduction as key steps. These syntheses enabled the unambiguous characterization of this natural product for the first time and helped establish 7( S )-HDHA as a possible endogenous ligand for peroxisome proliferator-activated receptor alpha.,10.1021/acs.joc.0c01770,2020-09-21,0.621737020591123
Angewandte Chemie International Edition,"Synthesis of a Cyclopropene Analogue of Ceramide, a Potent Inhibitor of Dihydroceramide Desaturase","The replacement of the double bond of ceramide by a cyclopropene (for example, erythro-1) has resulted in the first potent inhibitor of dihydroceramide desaturase, which is a key enzyme in the biosynthesis of sphingolipids.",10.1002/1521-3773(20010518)40:10<1960::aid-anie1960>3.0.co;2-v,2001-05-18,0.6217228728879935
Angewandte Chemie International Edition,"Synthesis of a Cyclopropene Analogue of Ceramide, a Potent Inhibitor of Dihydroceramide Desaturase","The replacement of the double bond of ceramide by a cyclopropene (for example, erythro-1) has resulted in the first potent inhibitor of dihydroceramide desaturase, which is a key enzyme in the biosynthesis of sphingolipids.",10.1002/1521-3773(20010518)40:10<1960::aid-anie1960>3.3.co;2-m,2001-05-18,0.6217228728879935
Tetrahedron,"Novel efficient synthesis of 1-azabicyclo[1.1.0]butane and its application to the synthesis of 1-(1,3-thiazolin-2-yl)azetidine-3-thiol useful for the pendant moiety of an oral 1β-methylcarbapenem antibiotic L-084",,10.1016/s0040-4039(99)00603-6,1999-05-01,0.6217156569959661
Tetrahedron,A new enantioselective route to the Sceletium alkaloids via a cyclopentanone–cyclohexenone transformation,,10.1016/s0040-4039(02)00033-3,2002-02-01,0.6216831654004644
Organic Process Research & Development,"Practical Synthesis of Chiral 2-Morpholine: (4-Benzylmorpholin-2-(<i>S</i>)-yl)-(tetrahydropyran-4-yl)methanone Mesylate, a Useful Pharmaceutical Intermediate","A commercial synthesis was developed for the production of (4-benzylmorpholin-2-( S )-yl)-(tetrahydropyran-4-yl)methanone mesylate, 1a, a key starting material for a phase 2, new investigational drug candidate at Eli Lilly and Company. The target compound was produced in the clinical pilot plant by the combination of two key steps: resolution of a morpholine amide intermediate to install the S -morpholino stereocenter in 35% yield and a high-yielding (89%) Grignard reaction to generate the title compound 1a, isolated as a mesylate salt. The Grignard reaction was found to proceed optimally when using a combination of I 2 and DIBAL-H for the initiation. In addition, the Grignard reagent formation was monitored by ReactMax calorimetry, and proof-of-concept studies were completed, demonstrating that the Grignard step could potentially be run as a continuous process with magnesium recycling.",10.1021/op800247w,2009-01-23,0.6216749350512822
Angewandte Chemie International Edition,Total Synthesis of Phorboxazole B,"Challenge met: In the synthesis of phorboxazole B, a highly efficient hetero-Diels–Alder reaction was used to construct the key C33–C39 linchpin, allowing for the completion of the C18–C46 fragment (see picture). Coupling with a suitable C3–C17 partner was followed by late-stage formation of the oxazole unit, macrocyclization, and deprotection to afford synthetic phorboxazole B.",10.1002/anie.200603656,2006-12-13,0.621671640804223
Tetrahedron,Towards the total synthesis of amphidinolide E: an enantioselective synthesis of C12–C29 fragment,,10.1016/j.tetlet.2004.08.143,2004-09-14,0.6216597346223348
Organic Letters,"Total Synthesis of 7,11-Cyclobotryococca-5,12,26-triene Using an Oxidative Radical Cyclization as a Key Step","An efficient total synthesis of the novel botryococcene-related hydrocarbon 7,11-cyclobotryococca-5,12,26-triene is reported that uses, as a key step, an oxidative radical cyclization of a 4-pentenyl malonate for the synthesis of a [3.3.0]-bicyclic gamma-lactone.",10.1021/ol100794k,2010-05-18,0.6216585243969285
Journal of Organic Chemistry,C7-Derivatization of C3-Alkylindoles Including Tryptophans and Tryptamines,"A versatile strategy for C7-selective boronation of tryptophans, tryptamines, and 3-alkylindoles by way of a single-pot C2/C7-diboronation-C2-protodeboronation sequence is described. The combination of a mild iridium-catalyzed C2/C7-diboronation followed by an in situ palladium-catalyzed C2-protodeboronation allows efficient entry to valuable C7-boroindoles that enable further C7-derivatization. The versatility of the chemistry is highlighted by the gram-scale synthesis of C7-boronated N-Boc-L-tryptophan methyl ester and the rapid synthesis of C7-halo, C7-hydroxy, and C7-aryl tryptophan derivatives.",10.1021/jo502062z,2014-10-24,0.6216569248635372
Organic Process Research & Development,Highly Regioselective and Practical Synthesis of 5-Bromo-4-chloro-3-nitro-7-azaindole,"We report an efficient and highly regiocontrolled route to prepare a functionalized 7-azaindole derivative—5-bromo-4-chloro-3-nitro-7-azaindole—from readily available parent 7-azaindole featuring a highly regioselective bromination of the 4-chloro-3-nitro-7-azaindole intermediate. In addition to the high efficiency and excellent control of regioisomeric impurities, the process is operationally simple by isolating each product via direct crystallization from the reaction mixture with no liquid–liquid extractions or distillation steps needed. We demonstrated the route on >50 kg scale and 46% overall yield to provide the target product in 97% purity by HPLC, which can serve as a useful building block for the preparation of a series of 3,4,5-substituted-7-azaindole derivatives.",10.1021/acs.oprd.7b00060,2017-03-28,0.6216402414712461
Journal of Organic Chemistry,Stereoselective Synthesis of (+)-Goniothalesdiol,"Stereoselective synthesis of antitumor tetrahydrofuran (+)-goniothalesdiol was achieved in high overall yield from (-)-D-tartaric acid. Key features include an FeCl3 mediated THF formation with very high selectivity. Synthesis of natural gonithalesdiol and its analogue 2,5-bis-epi-goniothalesdiol was achieved from a common intermediate.",10.1021/jo060159f,2006-03-30,0.6216351255682312
European Journal of Organic Chemistry,"Synthesis of β‐Lapachone, a Potential Anticancer Agent from the Lapacho Tree","Abstract A pharmaceutically important natural product, β‐lapachone, was efficiently synthesized in four steps in 70 % overall yield starting from commercially available 1,4‐naphthoquinone. The key step of the synthesis was the direct conversion of 2‐prenyl‐1,4‐naphthoquinone into β‐lapachone through an advantageous cyclization/hydration/oxidation cascade process.",10.1002/ejoc.201403064,2014-10-09,0.6215891001475411
Angewandte Chemie International Edition,Total Synthesis of (+)‐Dendrowardol C,"Abstract The first total synthesis of the tetracyclic sesquiterpenoid (+)‐dendrowardol C is described. It relies on an intramolecular aldol reaction to forge the central bicyclic scaffold and subsequent cyclobutane formation by cyclization of a γ‐triflyloxy ketone. Key is the treatment of the latter with lithium naphthalenide. Finally, the diastereoselective hydroboration of a 1,1‐disubstituted double bond is enabled by a chiral Co I catalyst.",10.1002/anie.201705809,2017-07-10,0.621583767825963
Journal of the American Chemical Society,Highly Selective Copper-Catalyzed Ring Expansion of Vinyl Thiiranes:  Application to Synthesis of Biotin and the Heterocyclic Core of Plavix,"We report herein a new, highly selective, mild copper-catalyzed vinyl thiirane ring-expansion protocol for the formation of 2,5-dihydrothiophenes. Preliminary substrate scope and applications of this new synthetic disconnection to the formal racemic total synthesis of biotin and the synthesis of the antiplatelet blockbuster pharmaceutical agent Plavix are described.",10.1021/ja069059h,2007-02-16,0.6215821906151358
Tetrahedron,"A novel synthesis of 4-chloro-4-hethylcyclohexa-2,5-dienone and 4,4-dimethoxycyclohexa-2,5-dienone.",,10.1016/s0040-4039(00)72070-3,1975-01-01,0.6215811121084106
Synthesis,Formal Total Synthesis of (±)-Rhazinal: Evaluating the Radical Approach,We describe a formal total synthesis of the racemic natural product rhazinal by a rapid elaboration of a recently reported tetrahydroindolizine intermediate into the cyclization precursor reported by Trauner. The synthesis focuses on the early and convergent introduction of functional groups while the synthetic challenges encountered by this approach are described.,10.1055/s-0036-1588956,2017-03-02,0.6215790529624436
Angewandte Chemie International Edition,Total Synthesis of Lycoricidine and Narciclasine by Chemical Dearomatization of Bromobenzene,"The total synthesis of lycoricidine and narciclasine is enabled by an arenophile-mediated dearomative dihydroxylation of bromobenzene. Subsequent transpositive Suzuki coupling and cycloreversion deliver a key biaryl dihydrodiol intermediate, which is rapidly converted into lycoricidine through site-selective syn-1,4-hydroxyamination and deprotection. The total synthesis of narciclasine is accomplished by the late-stage, amide-directed C-H hydroxylation of a lycoricidine intermediate. Moreover, the general applicability of this strategy to access dihydroxylated biphenyls is demonstrated with several examples.",10.1002/anie.201709712,2017-10-11,0.6215783712459146
Journal of Organic Chemistry,Asymmetric Synthesis of the Aromatic Fragment of Sespendole,"Sespendole is an indole sesquiterpene alkaloid bearing two isoprenyl groups, one of which is highly oxidized. Herein, we disclose an eight-step synthesis of the aromatic fragment of sespendole in an optically pure form, starting from 4-bromo-2-fluoronitrobenzene. The key steps were a Claisen rearrangement at room temperature for introduction of the prenyl group and a coupling between the dianion generated from prenylated bromo- N -tosylanilide and a chiral epoxy aldehyde.",10.1021/acs.joc.9b01597,2019-07-03,0.6215757614214503
Journal of Organic Chemistry,"Bidirectional Synthesis of Di-<i>tert</i>-butyl (2<i>S</i>,6<i>S</i>,8<i>S</i>)- and (2<i>R</i>,6<i>R</i>,8<i>R</i>)-1,7-Diazaspiro[5.5]undecane-2,8-dicarboxylate and Related Spirodiamines","Efficient syntheses of both enantiomers of a spirodiamine diester from (l)- and (d)-aspartic acid are described. The key transformation was the conversion of Boc-protected tert-butyl aspartate into the derived aldehyde, two-directional Horner-Wadsworth-Emmons olefination, hydrogenation, and selective acid-catalyzed Boc-deprotection and spirocyclization. An alternative, two-directional approach to derivatives of 1,7-diazaspiro[5.5]undecane is described.",10.1021/acs.joc.8b00794,2018-05-23,0.6215642953452445
Journal of Organic Chemistry,Asymmetric Synthesis of a Series of Chiral AB<sub>2</sub>Monomers for Dendrimer Construction,"Efficient preparation of a series of four chiral, nonracemic AB 2 monomers suitable for the construction of dendrimers is presented. Monomers 1 − 4 possess the common structural features of a diphenolic moiety and a benzylic or aliphatic hydroxyl which render these molecules suitable for convergent dendrimer synthesis. The same basic, high-yielding, five-step sequence is employed for 1 − 4 . Stilbene derivatives 13 and 14 are prepared by a Horner−Wadsworth−Emmons modified Wittig reaction between 3,5- or 3,4-bis(benzyloxy)benzaldehyde ( 8 and 10 ) and an ester-substituted benzylphosphonate ( 11 or 12 ). Cinnamate derivatives 21 and 22 are prepared similarly from 8 and 10 and triethyl phosphonoacetate. Chirality is introduced in the form of a 1,2-diol unit by Sharpless asymmetric dihydroxylation (AD) (>97% ee in all cases). Protection of the 1,2-diols as their acetonide derivatives provides dioxolane intermediates 17, 18, 25, and 26 . Reduction of the ester groups followed by hydrogenolysis of the benzyl ethers yields AB 2 monomers 1 − 4 in 57−67% overall yield from 8 and 10 .",10.1021/jo961587w,1997-02-01,0.6215595575934391
Journal of the American Chemical Society,Asymmetric Synthesis of (−)-Incarvillateine Employing an Intramolecular Alkylation via Rh-Catalyzed Olefinic C−H Bond Activation,"An asymmetric total synthesis of (-)-incarvillateine, a natural product having potent analgesic properties, has been achieved in 11 steps and 15.4% overall yield. The key step is a rhodium-catalyzed intramolecular alkylation of an olefinic C-H bond to set two stereocenters. Additionally, this transformation produces an exocyclic, tetrasubstituted alkene through which the bicyclic piperidine moiety can readily be accessed.",10.1021/ja8012159,2008-04-29,0.6215569617943604
Tetrahedron,Asymmetric route to the hydroindolone core of the Amaryllidaceae alkaloids employing chiral bicyclic lactams,,10.1016/s0040-4039(99)02328-x,2000-03-01,0.6215569196439263
Journal of Organic Chemistry,Efficient and β-Stereoselective Synthesis of 4(5)-(β-<scp>d</scp>-Ribofuranosyl)- and 4(5)-(2-Deoxyribofuranosyl)imidazoles<sup>1</sup>,"A synthetic route to 4(5)-(beta-D-ribofuranosyl)imidazole (1), starting from 2,3,5-tri-O-benzyl-D-ribose (5), was developed via a Mitsunobu cyclization. Reaction of 5 with the lithium salt of bis-protected imidazole afforded the corresponding 5-ribosylimidazole 7RS. Hydrolysis of 7RS gave a 1:1 mixture of diol isomers 8R and 8S having an unsubstituted imidazole. Mitsunobu cyclization of the mixture 8RS using N,N,N',N'-tetramethylazodicarboxamide and Bu(3)P exclusively afforded benzylated beta-ribofuranosyl imidazole 9beta in 92% yield, accompanied by alpha-anomer 9alpha, in a ratio of 26.3:1. The configuration of 9beta was established by X-ray crystallography of ethoxycarbonyl derivative 10beta. Reductive debenzylation of 9beta over Pd/C was carried out, and the synthesis of 1 was attained from starting 5 in four steps and 87% overall yield. This synthetic methodology was extended to the synthesis of 4(5)-(2-deoxy-beta-D-ribofuranosyl)imidazole (2). Mitsunobu cyclization of a 1:1 mixture of the corresponding diol isomers 14RS produced 15beta and 15alpha in a ratio of 5.4:1. The synthesis of 2 was attained in a 59% overall yield from the starting 3,5-di-O-benzyl-2-deoxy-D-ribose (12). beta-Stereoselective glycosylation in the key step is discussed and explained by intramolecular hydrogen bonding between an NH in the imidazole and the oxygen functional group in the sugar moiety.",10.1021/jo952136z,1996-01-01,0.621549276778517
Organic Letters,"Total Synthesis of Fawcettimine-Type Alkaloid, Lycojaponicumin A","The efficient total synthesis of lycojaponicumin A ( 1 ) has been accomplished for the first time. The remarkable features of this novel strategy include the following: (1) rapid construction of tricyclic intermediate 4 through a regio- and stereoselective semipinacol ring expansion, which simplified the construction of rings A and B of 1; (2) the subsequent regio- and stereoselective formation of the highly strained rings C–E of 1 through a tandem oxa-hetero [3 + 2] cycloaddition/N-cycloalkylation.",10.1021/acs.orglett.0c00961,2020-04-24,0.6215489053567435
Organic Letters,Synthesis of an Advanced Intermediate en Route to the Mitomycin Natural Products,[Structure: see text] An advanced intermediate in our planned synthesis of mitomycin C has been acquired in nine steps from tert-butyl glyoxylate. The aziridinyl pyrrolidine and quinone subunits are coupled regioselectively to arrive at an enamine that is prepared for C10 homologation.,10.1021/ol0624676,2006-11-29,0.621548811198408
Journal of the American Chemical Society,Total Syntheses of (+)-Tedanolide and (+)-13-Deoxytedanolide,"Convergent total syntheses of the potent cytotoxins (+)-tedanolide (1) and (+)-13-deoxytedanolide (2) are described. The carbon framework of these compounds was assembled via a stereoselective aldol reaction that unifies the C(1)-C(12) ketone fragment 5 with a C(13)-C(23) aldehyde fragment 6 (for 13-deoxytedanolide) or 52 (for tedanolide). Multiple obstacles were encountered en route to (+)-1 and (+)-2 that required very careful selection and orchestration of the stereochemistry and functionality of key intermediates. Chief among these issues was the remarkable stability and lack of reactivity of hemiketals 33b and 34 that prevented the tedanolide synthesis from being completed from aldol 4. Key to the successful completion of the tedanolide synthesis was the observation that the 13-deoxy hemiketal 36 could be oxidized to C(11,15)-diketone 38 en route to 13-deoxytedanolide. This led to the decision to pursue the tedanolide synthesis via C(15)-(S)-epimers, since this stereochemical change would destabilize the hemiketal that plagued the attempted synthesis of tedanolide via C(15)-(R) intermediates. However, use of C(15)-(S)-configured intermediates required that the side-chain epoxide be introduced very late in the synthesis, owing to the ease with which the C(15)-(S)-OH cyclized onto the epoxide of intermediate 50.",10.1021/ja8063205,2008-11-04,0.6215438038436175
Organic Letters,Total Synthesis of (−)-Rhazinilam and Formal Synthesis of (+)-Eburenine and (+)-Aspidospermidine: Asymmetric Cu-Catalyzed Propargylic Substitution,A total synthesis of (-)-rhazinilam and formal syntheses of (+)-eburenine and (+)-aspidospermidine that rely on a copper(I)-catalyzed asymmetric propargylic substitution as the key step are reported. A salient feature of the reaction is the asymmetric construction of a quaternary stereocenter in high yield and enantiomeric excess.,10.1021/acs.orglett.7b02619,2017-10-02,0.6215415057935938
Tetrahedron,An efficient and robust synthesis of amorfrutin A,,10.1016/j.tetlet.2019.04.028,2019-04-17,0.6215085548853461
European Journal of Organic Chemistry,Synthesis of Enantiomerically Pure (−)-Wine Lactone Based on a Palladium-Catalyzed Enantioselective Allylic Substitution,"The first enantioselective synthesis of enantiomerically pure (−)-wine lactone, (−)-1a, a fragrance constituent of various white wines, and its epimer (+)-1b, was carried out. The key steps are allylic substitution of (±)-2-cyclohexen-1-yl acetate (2) with dimethylmalonate using palladium complexes of phosphanyldihydrooxazol L1 or of the phosphanylcarboxylic acid L2 as catalyst, subsequent decarboxylation, iodolactonization and elimination, furnishing enantiomerically pure bicyclic lactone (+)-7 in 47% overall yield. The diastereoselective introduction of methyl groups by SN2′-type substitution with an organocopper compound and by enolate alkylation gave lactone (−)-1a in 43% overall yield from (+)-7.",10.1002/(sici)1099-0690(200002)2000:3<419::aid-ejoc419>3.0.co;2-n,2000-02-01,0.6215084467374546
Tetrahedron,"A norbornyl route to cyclopentitols via novel regiospecific fragmentation of a 2,7-disubstituted norbornane",,10.1016/s0040-4039(99)01115-6,1999-07-01,0.6215053089248381
Organic Process Research & Development,"Development of a Kilogram-Scale Synthesis of a Novel Anti-HCV Agent, CH4930808","Herein, we report the kilogram-scale synthesis of CH4930808 ( 1 ), a novel anti-hepatitis C virus agent. While pursuing improved productivity using many through-process strategies, we conducted scrupulous impurity control. Finally, we successfully developed a practical and scalable process for the synthesis of ( 1 ·1.5Na·2.5H 2 O), by which we prepared 3.28 kg of the active pharmaceutical ingredient for clinical studies.",10.1021/acs.oprd.7b00383,2018-01-16,0.6215049378404011
Organic Letters,"Total Synthesis of Nafuredin, a Selective NADH-fumarate Reductase Inhibitor","[structure: see text] Total synthesis of nafuredin, a selective NADH-fumarate reductase inhibitor, has been accomplished by a convergent approach. The C1-C8 and C9-C18 segments were derived efficiently from D-glucose and (S)-(-)-2-methyl-1-butanol, respectively, coupled by stereoselective Julia olefination, and converted to nafuredin.",10.1021/ol010089t,2001-06-30,0.6215047873869434
Organic Letters,"Biomimetic Synthesis of Macahydantoins A and B from <i>Lepidium meyenii</i>, and Structure Revision of Macahydantoin B as a Class of Thiohydantoin with a 4-Methyl-hexahydropyrrolo[1,2-<i>c</i>]imidazole Skeleton","Phytochemical investigation on Lepidium meyenii led to the discovery of macahydantoin C (3), a new thiohydantoin with a 1,3-diazabicyclo[3.3.1]nonane core, the spectral properties of which indicate a potential structural misassignment of its previously reported analogue, macahydantoin B (2a). To probe this hypothesis, a concise, scalable, and biomimetic synthesis of the originally proposed 2a and its revised structure (2b) was efficiently accomplished using the modified Edman degradation as the key step from commercially available materials in 65% (three steps) and 52% (three steps) overall yields, respectively. These synthetic endeavors undoubtedly reassigned the structure of macahydantoin B as an unreported type of thiohydantoin featuring a 4-methyl-hexahydropyrrolo[1,2-c]imidazole scaffold.",10.1021/acs.orglett.7b02433,2017-09-06,0.6215030215437208
Tetrahedron,"5A,5D-dicarboxy-β-cyclodextrin derivatives - a route for regioselectively difunctionalized permethyl-β-cyclodextrin",,10.1016/s0040-4039(01)93941-3,1989-01-01,0.6214987488179976
Tetrahedron,A stereo-divergent route to aminocyclopentitol derivatives,,10.1016/j.tetlet.2011.05.103,2011-06-04,0.6214987488179976
Tetrahedron,Solvolytic π-route to dibenzobicyclo[2.2.2]octadiene and dibenzobicyclo[3.2.1]octadiene derivatives,,10.1016/s0040-4039(01)88034-5,1969-01-01,0.6214987488179976
Tetrahedron,A stereodivergent route to two epimeric 2-pyrrolidinylglycine derivatives,,10.1016/j.tetlet.2009.08.030,2009-08-27,0.6214987488179976
Synlett,"Total Synthesis of α-C-Mannosyltryptophan, a Naturally Occurring C-Glycosyl Amino Acid","All articles of this category A stereocontrolled synthesis of α - C -mannosyltryptophan, a new type of glycosyl amino acid, was achieved by Sc(ClO 4 ) 3 mediated coupling between α - C -mannosylindole and l-serine-derived 2-aziridinecarboxylate as a key step. C -glycoside - aziridine - scandium perchlorate - natural product - total synthesis",10.1055/s-2001-14629,2001-01-01,0.6214899307375367
Tetrahedron,A simple synthetic route to substituted cyclopentenolones,,10.1016/s0040-4039(01)90053-x,1984-01-01,0.621488845398323
Organic Letters,Progress toward Synthesis of Diazonamide A. Preparation of a 3-(Oxazol-5-yl)-4-trifluoromethylsulfonyloxyindole and Its Use in Biaryl Coupling Reactions,"[formula: see text] The synthesis of a 3-oxazol-5-yl-indole-4-triflate is described, featuring a Schölkopf reaction to prepare the oxazole. In addition, the participation of this intermediate in biaryl coupling reactions toward the total synthesis of the natural product diazonamide A is presented.",10.1021/ol005548p,2000-03-28,0.6214830728499872
Angewandte Chemie International Edition,Total Synthesis of (−)‐Episilvestrol and (−)‐Silvestrol,"Sugar and spice…︁ The total synthesis of the rare but potent anticancer natural product (−)-episilvestrol and its 5′′′ epimer (−)-silvestrol was accomplished from D-glucose, naringenin, and methyl cinnamate (see scheme). The key steps of the sequence were inspired by the possible biogenesis of these compounds.",10.1002/anie.200702700,2007-09-06,0.621479138875799
Journal of the American Chemical Society,Total Synthesis of (−)-Xylogranatopyridine B via a Palladium-Catalyzed Oxidative Stannylation of Enones,"We report a total synthesis of the pyridine-containing limonoid alkaloid (-)-xylogranatopyridine B in 11 steps from commercially available dihydrocarvone. The central pyridine ring was assembled by a late-stage fragment coupling approach employing a modified Liebeskind pyridine synthesis. One fragment was prepared by an allyl-palladium catalyzed oxidative enone β-stannylation, in which the key bimetallic β-stannyl palladium enolate intermediate undergoes a β-hydride elimination. This methodology also allowed introduction of alkyl and silyl groups to the β-position of enones.",10.1021/jacs.7b13189,2018-01-16,0.6214702530931965
European Journal of Organic Chemistry,Synthesis of Coenzyme Q<sub>10</sub>,"Abstract A practical synthesis of coenzyme Q 10 has been developed. The route features an improved Friedel–Crafts allylation of tetramethoxytoluene with a para ‐chlorobenzenesulfonyl‐substituted C 5 allylic chloride at 40 °C. Replacement of the methyl ether protecting groups of the para ‐hydroquinone by methoxymethyl groups at Q 1 stage proceeded efficiently, and allowed the facile final oxidation to coenzyme Q 10 to occur under mild acidic conditions. The overall yield of coenzyme Q 10 from commercially available tetramethoxytoluene reached 53 % in this improved procedure.",10.1002/ejoc.201200627,2012-07-26,0.6214672548353087
Synthesis,Stereoselective Synthesis of Diltiazem via Dynamic Kinetic Resolution,"An efficient synthesis of diltiazem has been developed using dynamic kinetic resolution (DKR) as a key step. The methyl (2S,3S)-2-chloro-3-hydroxy-3-(4-methoxyphenyl)propionate was synthesized from a racemic mixture of α-chloro-β-keto ester, with high anti diastereoselectivity (92%) and enantioselectivity (95%), based on an asymmetric hydrogenation reaction with a chiral ruthenium(II) catalyst, simply prepared by mixing Ru(cod)(2-methylallyl)2 with the atropisomeric ligand (S)-MeO-BIPHEP. By treatment of this α-chloro-β-hydroxy ester with a base, the corresponding trans methyl glycidate, a key intermediate of diltiazem, was easily obtained.",10.1055/s-2003-42397,2003-01-01,0.621461280235664
Organic Letters,A New Synthesis of Chlorins,"A new synthesis of chlorins has been developed, based upon the acid-catalyzed condensation of dialdehydes AB with dipyrromethanes CD.",10.1021/ol006983m,2001-02-21,0.6214597420027864
Journal of the American Chemical Society,Total Synthesis of Vinigrol,"The longstanding challenge posed by the complex diterpene vinigrol has been answered for the first time. The notorious difficulty in synthesizing vinigrol stems from its unprecedented decahydro-1,5-butanonaphthalene ring system, eight contiguous stereocenters, and highly congested functionality. This Communication delineates a stereocontrolled 23-step route to vinigrol that is scalable (>5 g prepared of a late-stage intermediate), minimally reliant on protecting group chemistry, and facilitated by a number of unique and chemoselective transformations.",10.1021/ja908194b,2009-10-30,0.6214581553011881
Journal of Organic Chemistry,Diastereoselective Synthesis of the HIV Protease Inhibitor Darunavir and Related Derivatives via a Titanium Tetrachloride-Mediated Asymmetric Glycolate Aldol Addition Reaction,"High Resolution Image Download MS PowerPoint Slide Darunavir is a potent HIV protease inhibitor that has been established as an effective tool in the fight against the progression of HIV/AIDS in the global community. The successful application of this drug has spurred the development of derivatives wherein strategic regions (e.g., P1, P1’, P2, and P2’) of the darunavir framework have been structurally modified. An alternate route for the synthesis of darunavir and three related P1 and P1’ derivatives has been developed. This synthetic pathway involves the use of a Crimmins titanium tetrachloride-mediated oxazolidine-2-thione-guided asymmetric glycolate aldol addition reaction. The resultant aldol adduct introduces the P1 fragment of darunavir via an aldehyde. Transamidation with a selected amine (isobutylamine or 2-ethyl-1-butylamine) to cleave the auxiliary yields an amide wherein the P1’ component is introduced. From this stage, the amide is reduced to the corresponding β-amino alcohol and the substrate is then bis-nosylated to introduce the requisite p -nitrobenzenesulfonamide component and activate the secondary alcohol for nucleophilic substitution. Treatment with sodium azide yielded the desired azides, and the deprotection of the p -methoxyphenoxy group is achieved with the use of ceric ammonium nitrate. Finally, hydrogenation to reduce both the aniline and azide functionalities with concurrent acylation yields darunavir and its derivatives.",10.1021/acs.joc.4c01057,2024-06-25,0.6214562385360336
Organic Letters,Total Synthesis of (−)-SNF4435 C and (+)-SNF4435 D,"[reaction: see text] A convergent, biomimetic total synthesis of the immunosuppressant polyketides SNF4435 C and D is described. The synthetic pathway features a stereo- and regioselective [3,3]-sigmatropic rearrangement as well as a high-yielding Stille coupling/8pi-6pi electrocyclization cascade.",10.1021/ol051790q,2005-08-27,0.6214527335368966
Organic Letters,Application of Ynamides in the Synthesis of 2-Amidoindoles,"A Pd-catalyzed, one-pot, two-step synthesis of 2-amidoindoles from ynamides and o-iodoanilines is reported. A key highlight of this sequence is that after the Sonogashira reaction, intramolecular cyclization to the indole occurs spontaneously without activation of the alkyne.",10.1021/ol802477d,2008-11-26,0.6214470857738488
Tetrahedron,An efficient synthesis of lamellarin alkaloids: synthesis of lamellarin G trimethyl ether,,10.1016/s0040-4039(00)02222-x,2001-02-01,0.6214444883596613
Organic Letters,A Convenient Synthesis of A-Ring-Functionalized Podolactones. Revision of the Structure of Wentilactone B,"A new route to podolactones functionalized in the A ring has been achieved. Two key steps were employed in this synthesis, the construction of the bicyclic skeleton via a Mn(III)-mediated radical cyclization and the transformation of this bicyclic intermediate into the tetracyclic podolactone skeleton through a Pd (II)-mediated bislactonization of the corresponding conjugate diene. The reported synthesis of 3beta-hydroxy-13,14,15,16-tetranorlabda-7,9(11)-dien-(19,6beta),(12,17)-diolide (1) let us reassign the structure of wentilactone B, for which structure 1 was wrongly reported. [reaction: see text]",10.1021/ol0257070,2002-03-23,0.6214394369272878
Tetrahedron,Asymmetric synthesis of the mC7N core of the manumycin family: Preparation of (+)-MT 35214 and a formal total synthesis of (−)-alisamycin,,10.1016/s0040-4039(98)01047-8,1998-07-01,0.621419887354345
Journal of the American Chemical Society,Total Synthesis of Taxol Enabled by Intermolecular Radical Coupling and Pd-Catalyzed Cyclization,"Taxol ( 1 ) is a clinically used antineoplastic diterpenoid. The tetracyclic ring system comprises a 6/8/6-membered carbocycle (ABC-ring) and a fused oxetane ring (D-ring) embedded with a bridgehead double bond and decorated with multiple oxygen functionalities. Here, we report a convergent total synthesis of this exceedingly complex natural product. The C-ring fragment was designed to possess a bromocyclohexenone and an extra tetrahydrofuran ring to control the reactivity and selectivity, as well as to minimize functional group manipulations en route to 1 . The α-alkoxyacyl telluride of the A-ring served as a radical precursor, and intermolecular radical coupling with the C-ring realized the installation of the C2- and C3-stereocenters and reductive removal of the bromide. After the C8-quaternary stereocenter was constructed by exploiting the three-dimensional shape of the intermediate, the C11-vinyl triflate of A-ring and the C8-methyl ketone of C-ring were utilized for Pd(0)-catalyzed cyclization of the central eight-membered B-ring with the bridgehead olefin. Adjustment of the oxidation level and attachment of the oxetane D-ring completed the total synthesis of 1 (28 steps, as the longest linear sequence). The fragment design principle and implementation of the powerful radical coupling reaction described in the present synthesis provide valuable information for planning and executing syntheses of diverse densely oxygenated terpenoids.",10.1021/jacs.3c10658,2023-11-16,0.6214166158208925
Journal of the American Chemical Society,"Facile, Efficient, and Enantiospecific Syntheses of 1,1‘-<i>N</i>-Linked Pseudodisaccharides as a New Class of Glycosidase Inhibitors","This article describes an efficient synthesis of a potent trehalase inhibitor, 1,1'-N-linked pseudodisaccharide 1 (consisting of two valienamines), in 14 steps with an overall yield of 12% and a first synthesis of 2 (consisting of two 2-epi-valienamines) in 15 steps with an overall yield of 24% from (-)-quinic acid. The synthesis involves a stereospecific palladium-catalyzed coupling reaction between an allylic amine and an allylic chloride as the crucial step. The acetonide blocking groups were shown to be the best hydroxyl protecting groups, compatible with the palladium-catalyzed allylic amination reaction that afforded high yields of the 1,1'-N-linked pseudodisaccharides with a minimum amount of an elimination diene side product.",10.1021/ja0470158,2004-11-19,0.6214107776267274
Synthesis,Total Synthesis of gem-Difluoromethylenated Analogues of Pironetin,The straightforward synthesis of four gem-difluoromethylenated analogues of pironetin is described. Our synthesis features the efficient construction of the key intermediates through the indium­-mediated gem-difluoropropargylation of aldehydes with the fluorine-containing building block.,10.1055/s-0029-1217099,2009-11-03,0.6213938357187758
Synthesis,"A Synthesis of 5′-Amino-3′,5′-dideoxyuridine","All articles of this category The synthesis of 3′,5′-dideoxy-5′-aminouridine starting from uridine is described. 3′,5′-dideoxy-5′-aminouridine - mureidomycin - nucleoside - deoxygenation - azidation",10.1055/s-2000-6346,2000-01-01,0.6213913034979773
Synlett,"Enantioselective Synthesis of Chiral α-Aminoalkyl-1,2,3-triazoles Using a Three-Component Reaction","A range of chiral α-aminoalkyl-1,2,3-triazoles have been prepared in a modular fashion in 3 steps with up to 98% ee. The key step is a CuBr/Quinap-catalyzed enantioselective asymmetric three-component synthesis of propargylamines.",10.1055/s-2005-918931,2005-01-01,0.6213892511942374
Angewandte Chemie International Edition,Efficient Assembly of an Indole Alkaloid Skeleton by Cyclopropanation: Concise Total Synthesis of (±)‐Minfiensine,"Cascading into (±)-minfiensine: An efficient method was developed for the assembly of tetracyclic skeleton 1 by a three-step, one-pot cascade reaction including cyclopropanation, ring opening, and ring closure (see scheme; Ts=p-toluenesulfonyl). The concise total synthesis of the (±)-minfiensine was completed in about a 4 % overall yield.",10.1002/anie.200800566,2008-03-28,0.6213850658145701
Synthesis,Effective Synthetic Routes to Cubylcarbinol Derivatives,Three alternative routes for the synthesis of cubylcarbinol (1) from 4-iodocubanecarboxylic acid (5) are described.,10.1055/s-2002-35981,2002-01-01,0.6213848161169814
Tetrahedron,"Catalytic enantioselective synthesis of a novel inhibitor of ceramide trafficking, (1R,3R)-N-(3-hydroxy-1-hydroxymethyl-3-phenylpropyl)dodecanamide (HPA-12)",,10.1016/s0040-4039(01)01658-6,2001-10-01,0.6213837207944262
Organic Letters,Synthesis of a Tiacumicin B Protected Aglycone,"Tiacumicin B is an antibiotic endowed with the remarkable ability to interact with a new biological target, giving it an inestimable potential in the context of the ever-growing and worrisome appearance of resistances of bacteria and mycobacteria to antibiotics. The synthesis of an aglycone of tiacumicin B ready for glycosylation is reported. The key steps of this approach are a [2,3]-Wittig rearrangement, a Pd/Cu-catalyzed allene-alkyne cross-coupling, a E-selective cross-metathesis, and a final ring-size selective macrolactonization.",10.1021/acs.orglett.7b01744,2017-07-19,0.621373343521672
Synlett,An Efficient Synthetic Route to <i>N</i>-Glycosylamino Acids Using <i>N</i><sup>α</sup>-Fmoc-Asp/Glu-5-oxazolidinone as Internal Protection,"A new facile synthetic route to prepare N-glycosylamino acids in fewer steps is reported. 5-Oxazolidinone served as an effective protecting moiety for N α-Fmoc-Asp/Glu and after glycosylation, the ring opening resulted in free α-carboxylic acid, which can be directly used to extend the chain to obtain N-glycopeptides. Both the minimum number of steps as well as circumvention of ortho­gonal protection strategy leads to a cost-effective route for their synthesis. This protocol can be easily scaled up to prepare N-glyco­sylated Asn/Gln acids in large quantities in fairly good yields.",10.1055/s-2007-986645,2007-09-21,0.621372336200531
European Journal of Organic Chemistry,O‐Specific Polysaccharide of <i>Vibrio cholerae</i> O139: Improved Synthesis and Conjugation to BSA by Squaric Acid Chemistry,"The sequence α‐Col p ‐(1→2)‐4,6‐ P ‐β‐ d ‐Gal p ‐(1→3)‐[α‐Col p ‐(1→4)]‐β‐ d ‐Glc p NAc‐(1→4)‐α‐ d ‐Gal p A‐(1→3)‐β‐ d ‐Qui p NAc constitutes the complete O‐specific polysaccharide (O‐antigen, O‐SP) of Vibrio cholerae O139. It was chemically synthesized in a linker‐equipped, conjugation‐ready form ( 7 ) and conjugated to a model protein carrier, bovine serum albumin. The preparation involved the synthesis of a tetrasaccharide intermediate sequence β‐ d ‐Gal p ‐(1→3)‐β‐ d ‐Glc p NAc‐(1→4)‐α‐ d ‐Gal p A‐(1→3)‐β‐ d ‐Qui p NAc→linker by coupling of two disaccharide intermediates followed by a stepwise, two single‐site colitosylations. The present synthesis is an alternative to the academic, small‐scale synthesis developed earlier where the final hexasaccharide assembly was achieved by simultaneous, two‐sites colitosylation. The approach reported herein comprises a few more synthetic steps but is experimentally less demanding, minimizes separation difficulties and is more convenient when tens of mgs of the final product is required. Syntheses of non‐phosphorylated and methyl ester analogues of 7 are also described.",10.1002/ejoc.201800429,2018-04-10,0.6213721108740446
European Journal of Organic Chemistry,"Synthesis of Previously Inaccessible Derivatives of 1,4,7‐<i>Tri</i>‐R‐1,4,7‐Triazacyclononane, Including Chiral Examples, and a Rapid Synthesis of the HCl Salts of H<sub>3</sub>tacn and H<sub>4</sub>dtne","The synthesis of 1,4‐di‐ tert ‐butyl‐7‐R‐1,4,7‐triazacyclononane ( t Bu 2 Rtacn) derivatives through a “crab‐like” cyclization is reported. The tert ‐butyl groups were cleavable with concentrated hydrochloric acid, allowing for a facile and convenient synthesis of the HCl salt of H 3 tacn and the most direct route to its industrially relevant binucleating N ‐ethylene bridged derivative, H 4 dtne. In addition, the synthesis of chiral tacn derivatives with both one and two stereocenters in non‐annulet, alpha‐N positions is reported.",10.1002/ejoc.201801323,2018-10-10,0.6213617010445708
Tetrahedron,A novel route to synthesis of flavones from salicylaldehyde and acetophenone derivatives,,10.1016/j.tetlet.2012.02.108,2012-03-06,0.6213610230793134
Journal of Organic Chemistry,Total Synthesis of Phospholipomannan of <i>Candida albicans</i>,"First, total synthesis of the cell surface phospholipomannan anchor [β-Man p -(1 → 2)-β-Man p ] n -(1 → 2)-β-Man p -(1 → 2)-α-Man p -1 → P -( O → 6)-α-Man p -(1 → 2)-Inositol-1- P -( O → 1)-phytoceramide of Candida albicans is reported. The target phospholipomannan (PLM) anchor poses synthetic challenges such as the unusual kinetically controlled (1 → 2)-β-oligomannan domain, anomeric phosphodiester, and unique phytoceramide lipid tail linked to the glycan through a phosphate group. The synthesis of PLM anchor was accomplished using a convergent block synthetic approach using three main appropriately protected building blocks: (1 → 2)-β-tetramannan repeats, pseudodisaccharide, and phytoceramide-1- H -phosphonate. The most challenging (1 → 2)-β-tetramannan domain was synthesized in one pot using the preactivation method. The phytoceramide-1- H -phosphonate was synthesized through an enantioselective A 3 three-component coupling reaction. Finally, the phytoceramide-1- H -phosphonate moiety was coupled with pseudodisaccharide followed by deacetylation to produce the acceptor, which on subsequent coupling with tetramannosyl- H -phosphonate provided the fully protected PLM anchor. Final deprotection was successfully achieved by Pearlman’s hydrogenation.",10.1021/acs.joc.0c00402,2020-05-19,0.6213560020034172
Journal of the American Chemical Society,A Synthesis of (+)-Saxitoxin,"An asymmetric synthesis of the bis-guanidinium poison, (+)-saxitoxin (STX), is described. Commencing from an N,O-acetal starting material made readily available through sulfamate ester C-H amination, the completed route to STX showcases the utility of oxathiazinane dioxide heterocycles for the assembly of polyfunctionalized amine derivatives. In the final preparative stages, an unusual nine-membered ring guanidine intermediate is oxidized selectively and made to undergo dehydrative cyclization to afford the tricyclic core of the natural product. Access to STX and related structures will provide unique pharmacological tools for the study of voltage-regulated Na+ ion channel proteins.",10.1021/ja0608545,2006-03-01,0.6213469918437735
Organic Letters,Studies toward the Total Synthesis of the Marine Macrolide Salarin C,A convergent strategy for the synthesis of dideoxysalarin C (3) as a potential intermediate for the total synthesis of the marine macrolide salarin C (1) is described. The macrolactone core of 3 was assembled by Suzuki coupling between alkyl iodide 9 and vinyl iodide 8 and Shiina macrolactonization as key transformations. All macrocyclic intermediates were found to be of low stability.,10.1021/acs.orglett.8b03422,2018-11-26,0.6213447197143613
Journal of the American Chemical Society,"Annulation of Thioimidates and Vinyl Carbodiimides to Prepare 2-Aminopyrimidines, Competent Nucleophiles for Intramolecular Alkyne Hydroamination. Synthesis of (−)-Crambidine","A convergent synthesis of (-)-crambidine is reported. The sequence capitalizes on two novel key transformations, including a [4+2] annulation of thioimidates with vinyl carbodiimides and an alkyne hydroamination employing 2-aminopyrimidine nucleophiles.",10.1021/ja910831k,2010-01-22,0.6213434535185696
Organic Process Research & Development,"An Efficient, Economical Synthesis of the Novel Anti-tumor Agent CPI-613","An efficient and practical synthesis of the novel anti-tumor compound 6,8-dithiobenzyl octanoic acid, CPI-613 ( 2 ), was developed and executed on a practical scale. CPI-613 can be made in a single vessel from (±)-lipoic acid ( 1 ) via reductive opening of the disulfide ring followed by benzylation of the sulfhydryls with benzyl bromide. CPI-613 was isolated by simple crystallization in high yield and purity. The process is scaleable and has been demonstrated at up to 100 kg.",10.1021/op200091t,2011-05-02,0.6213375447727121
Journal of Organic Chemistry,Asymmetric Synthesis of All the Known Phlegmarine Alkaloids,"The asymmetric synthesis of all four of the known natural phlegmarines and one synthetic derivative has been accomplished in 19-22 steps from 4-methoxy-3-(triisopropylsilyl)pyridine. Chiral N-acylpyridinium salt chemistry was used twice to set the stereocenters at the C-9 and C-2' positions of the phlegmarine skeleton. Key reactions include the use of a mixed Grignard reagent for the second N-acylpyridinium salt addition, zinc/acetic acid reduction of a complex dihydropyridone, and a von Braun cyanogen bromide N-demethylation of a late intermediate. These syntheses confirmed the absolute stereochemistry of all of the known phlegmarines.",10.1021/jo1019688,2010-11-15,0.6213333214166554
European Journal of Organic Chemistry,An Improved Method for theendo-Fusion of Five-Membered Ring Lactones to the Bornane Ring System,endo-Fused lactone 3 was obtained in high yield from the camphoracetic acid 2 with thionyl chloride and a subsequent reduction of intermediate 5 with tributyltin hydride. The structure of 5 was elaborated and some aspects of the mechanism of its formation and reactivity were investigated. Lactone 3 serves as key intermediate for lactol 1 which is a useful reagent in racemate resolution and asymmetric synthesis.,10.1002/(sici)1099-0690(199811)1998:11<2507::aid-ejoc2507>3.0.co;2-8,1998-11-01,0.621332331468078
Tetrahedron,Asymmetric synthesis of the erythrinan alkaloid system using a chiral lithium amide base desymmetrisation as the key step,,10.1016/j.tetlet.2003.08.078,2003-09-22,0.6213194804011084
Organic Letters,Transannular Acylation Facilitates C<sub>5</sub>–C<sub>9</sub> Bond Formation in Hyperforin Total Synthesis,"Hyperforin is considered the flagship congener among polycyclic polyprenylated acylphloroglucinols due to its compelling and complex molecular architecture, coupled with remarkable biological activity, thus rendering it an appealing synthetic target for chemists over the past two decades. Herein, an innovative linear total synthesis of hyperforin is reported. Our synthesis relies on the formation of the bicyclo[3.3.1]nonane-2,4,9-trione framework via transannular acylation of a decorated eight-membered ring, followed by late stage bridgehead substitution.",10.1021/acs.orglett.5c00243,2025-02-27,0.6213169519680267
Organic Letters,Organosilanes in Synthesis:  Application to an Enantioselective Synthesis of Methyl-<scp>l</scp>-callipeltose,"[reaction: see text] Methyl-l-callipeltose, the carbohydrate associated with callipeltoside A, has been synthesized in eight steps and 23% overall yield from enantioenriched allylsilane 6 and acetaldehyde. The key steps are a highly diastereoselective formal [4 + 2] annulation and a Cr(VI)-catalyzed oxidative C-C bond cleavage to produce lactone 11.",10.1021/ol034582b,2003-05-01,0.6213157691028052
Journal of Organic Chemistry,"Total Synthesis of Macrosphelides A, B, and E:  First Application of Ring-Closing Metathesis for Macrosphelide Synthesis","A new synthetic route for macrosphelides A, B, and E based on ring-closing metathesis (RCM) was established. The substrates for RCM could be synthesized starting from commercially available chiral materials, methyl (S)-lactate and methyl (S)- or (R)-3-hydroxybutyrate, in good overall yields. In the investigation of the key RCM step, it was found that the steric factor around the reaction site significantly affected the reaction rate of macrocyclization. A detailed account regarding this synthetic study is described herein.",10.1021/jo035435u,2003-12-25,0.6213014327290455
Organic Letters,Total Synthesis of (+)-Peniciketal B,"An efficient synthesis of (+)-peniciketal B has been accomplished in 15 steps from the commercially available materials atraric acid, acryloyl chloride, and (+)-homoallylic alcohol. A convergent synthetic approach that is quite concise for constructing either “hemisphere” of (+)-peniciketal B with a common intermediate is employed that relies on a cascade intermolecular FeCl 3 -mediated “inner sphere” Michael-type reaction/double cyclization of an α,β-unsaturated ketone and substituted phenol to build the benzo-fused 2,8-dioxabicyclo[3.3.1]nonane with excellent diastereoselectivity. The generality of the transformation was also demonstrated by the broad scope of substrates that would be potential candidates for natural product synthesis and medicinal chemistry. Benzannulated [6,6]spiroketal was installed by a late-stage acid-catalyzed spiroketalization.",10.1021/acs.orglett.3c03472,2023-11-17,0.6212837301358438
Angewandte Chemie International Edition,Total Synthesis of the Nominal Didemnaketal A,"False identity: The synthesis of a natural product described by Faulkner and co-workers two decades ago has revealed the need for the revision of some stereochemical assignments. The key steps in this flexible route, which could provide access to stereodefined analogues for biological evaluation, included a Julia coupling, a Suzuki–Miyaura reaction, and Wittig olefination (see scheme; MOM, PMB, and TBS are protecting groups).",10.1002/anie.201203406,2012-09-26,0.6212824063988055
Synthesis,An Improved Synthesis of a Mixture of Diethyl (<i>Z</i>)- and (<i>E</i>)-3-Methylglutaconates from Ethyl Acetoacetate,"All articles of this category A simple, efficient two-step synthesis of a mixture of diethyl ( Z )- and ( E )-3-methylglutaconates from isodehydroacetic acid in 83 % yield is described. On the basis of this synthesis an improved procedure for the preparation of a mixture of ( Z )- and ( E )-3-methylglutaconic acids from ethyl acetoacetate in 44 % overall yield was elaborated.",10.1055/s-1993-35864,1993-01-01,0.6212755136110354
Journal of Organic Chemistry,"A General and Efficient Synthesis of Pyridin-2-yl <i>C</i>-Ribonucleosides Bearing Diverse Alkyl, Aryl, Amino, and Carbamoyl Groups in Position 6","An efficient and practical methodology of preparation of 6-substituted pyridin-2-yl C-ribonucleosides was developed. A one-pot two-step addition of 2-lithio-6-bromopyridine to TBS-protected ribonolactone followed by acetylation gave 1beta-(6-bromopyridin-2-yl)-1-O-acetyl-2,3,5-tri-O-(tert-butyldimethylsilyl)-D-ribofuranose in high yield. Its reduction with Et(3)SiH and BF(3) x Et(2)O afforded the desired TBS-protected 6-bromopyridine C-ribonucleoside as pure beta-anomer in good overall yield of 63%. This intermediate was then subjected to a series of palladium catalyzed cross-coupling reactions, aminations and aminocarbonylations to give a series of protected 1beta-(6-alkyl-, 6-aryl-, 6-amino-, and 6-carbamoylpyridin-2-yl)-C-ribonucleosides. Deprotection of silylated nucleosides by Et(3)N x 3HF gave a series of title free C-ribonucleosides (12 examples).",10.1021/jo902313g,2009-12-14,0.6212694956138078
Tetrahedron,"Efficient synthesis of ESI-09, a novel non-cyclic nucleotide EPAC antagonist",,10.1016/j.tetlet.2013.01.024,2013-01-21,0.6212600993852055
Angewandte Chemie International Edition,Total Synthesis of (+)‐β‐Erythroidine,"Enyne enyne oh! The first total synthesis of (+)-β-erythroidine, a non-aromatic Erythrina alkaloid, is demonstrated. The key steps involved are Lewis acid promoted cyclization of an epoxy–trichloroacetimidate intermediate and tandem ring-closing metathesis (RCM) of the dienyne (see scheme).",10.1002/anie.200600210,2006-03-21,0.6212592492535063
Organic Process Research & Development,Process for Developing 3β-[4-(<i>S</i>)-Arylacetylamino-4β-(2-(2-furyl)ethyl]azetidin-2-one:  A Carbacephem Key Intermediate,An optimized process for the stereospecific synthesis of carbacephem key intermediates 3β-[4-( S )-phenoxyacetylamino-4β-[2-(2-furyl)ethyl]azetidin-2-one ( 1 ) and 3β-[4-( S )-phenyl-acetylamino-4β-[2(2-furyl)ethyl)]azetidin-2-one] ( 2 ) is described. This report provides an efficient and cost-effective process for achieving a consistent yield and quality of intermediates 1 and 2 via Birch reduction employing a sodium/ammonia instead of lithium/ammonia system.,10.1021/op034074h,2003-10-02,0.6212536385947243
Synthesis,"Palladium-Catalyzed Amination in the Synthesis of Polyazamacrocycles Containing a 1,3-Disubstituted Benzene Moiety","The synthesis of a new family of polyaza- and polyoxa­polyazamacrocycles by a simple and efficient one-pot palladium-catalyzed diamination of 1,3-dibromobenzene is described. The dependence of the nature of the starting polyamines on the yield of the products is demonstrated. The synthesis of N α ,N ω -bis(3-bromophenyl)-substituted polyamines is elaborated to obtain intermediates for the synthesis of polyazamacrocycles consisting of two polyamine and two benzene fragments (cyclodimers). The formation of tri- and tetraarylated polyamines is studied and regularities of the process are established. The synthesis of 1,3-bis(polyamino)-substituted benzenes is also described.",10.1055/s-2007-990779,2007-09-24,0.6212486034905181
Synthesis,Facile Synthesis of 11-Hydroxy-2-methoxyaporphine: A Potential Dopamine D<sub>1</sub> Receptor Ligand,11-Hydroxy-2-methoxyaporphine was synthesized from oripavine in three steps with an overall yield of 37.8%. The key step involved the palladium on carbon catalyzed reduction of 11-hydroxy-2-methoxy-10-O-[(trifluoromethyl)sulfonyl]aporphine using magnesium metal in methanol at room temperature in the presence of ammonium acetate.,10.1055/s-2007-990902,2007-12-01,0.6212329305338063
Tetrahedron,"Use of an ephedrine alkoxide to mediate enantioselective addition of an acetylide to a prochiral ketone: asymmetric synthesis of the reverse transcriptase inhibitor L-743,726",,10.1016/0040-4039(95)01955-h,1995-12-01,0.6212177970067734
Organic Letters,Synthesis of the Core Structure of Daphnimacropodines,"Daphniphyllum alkaloids daphnimacropodines A-C possess a highly congested ring system and share a common tetracyclic ring skeleton. To access the challenging chemical structure of daphnimacropodines, a divergent synthetic approach toward their total synthesis is described. A stereoselective synthesis of the core structure of daphnimacropodines has been achieved from a simple diketone building block. Our approach features an intramolecular carbamate aza-Michael addition and a hydropyrrole synthesis via a Au-catalyzed alkyne hydration followed by an aldol condensation, whereas all the other attempts failed.",10.1021/acs.orglett.9b01486,2019-05-29,0.6212134105820329
Journal of Organic Chemistry,Chemoenzymatic Synthesis of Rivastigmine via Dynamic Kinetic Resolution as a Key Step,A practical and efficient procedure for the synthesis of rivastigmine was developed. This procedure includes dynamic kinetic resolution using a polymer-bound ruthenium complex and a lipase in combination as a key step. Enantiopure (-)-rivastigmine was obtained from commercially available 3'-hydroxyacetophenone via five steps in overall 57% yield.,10.1021/jo9027374,2010-03-26,0.6212070927340521
European Journal of Organic Chemistry,Stereocontrolled Total Synthesis of Sphingofungin E,"Abstract We describe herein the asymmetric total synthesis of sphingofungin E, which has potent immunosuppressive activity. Key steps include asymmetric desymmetrization by bromolactonization, stereocontrolled construction of four contiguous stereogenic centers through allylic C–H oxidation and epoxide ring opening, regioselective elongation of a dialdehyde, and Hofmann rearrangement by using PhI(OCOCF 3 ) 2 .",10.1002/ejoc.201301065,2013-09-19,0.621204634966698
Journal of Organic Chemistry,Total Synthesis of (+)-Przewalskin B,"An efficient strategy for the total synthesis of (+)-przewalskin B is reported. The key steps feature an intermolecular S(N)2' substitution of iodoallylic phosphate with organocupper reagent, a diastereoselective organocatalytic aldol cyclization, as well as a Rh(2)(OAc)(4)-mediated intramolecular carbene insertion to the tertiary C-H bond.",10.1021/jo201111w,2011-07-13,0.6212034638471039
Journal of Organic Chemistry,"Synthetic Strategies toward Spiroaspertrione A, Construction of the ABDE Ring System","The synthesis of the ABDE ring system of spiroaspertrione A is reported. Construction of the DE ring system features a cycloaddition-lactonization strategy, followed by an efficient cyclopropanation and subsequent ring expansion to construct the cycloheptylfuranone core. A Michael addition was employed to join the AB and DE fragments, which ultimately revealed a strategy for the introduction of a second Michael acceptor, which we envision to be a key precursor to spiroaspertrione A.",10.1021/acs.joc.5c01734,2025-08-23,0.6212026123183968
Synthesis,"Synthesis of Virgatol and Virgatenol, Two Naturally Occurring Coumarins from <i>Pterocaulon virgatum</i> (L.) DC, and 7-(2,3-Epoxy-3-methylbutoxy)-6-methoxycoumarin, Isolated from <i>Conyza obscura</i> DC","The synthesis of a number of naturally occurring coumarins from Pterocaulon virgatum (L.) and Conyza obscura DC is described for the first time. It concerns the synthesis of 7-(2-hydroxy-3-methoxy-3-methylbutoxy)-6-methoxycoumarin (virgatol, 1), 7-(2-hydroxy-3-methyl-3-butenyloxy)-6-methoxycoumarin (virgatenol, 2) and 7-(2,3-epoxy-3-methylbutoxy)-6-methoxycoumarin (3). In addition, a straightforward synthesis of scopoletin (4) (7-hydroxy-6-methoxycoumarin) is reported and the synthesis of a new coumarin derivative, 6-methoxy-7-(2-oxo-3-methylbutoxy)coumarin (7), is described.",10.1055/s-2004-829139,2004-07-13,0.6211992919095815
Journal of the American Chemical Society,Synthesis of the Lycopodium Alkaloid (+)-Lycoflexine,"The first total synthesis of (+)-lycoflexine (1), a constituent of Lycopodium clavatum var. inflexum , has been accomplished in eight steps with 13% overall yield. Our synthesis covers four one-pot reactions, including a tandem Sakurai/aldol sequence, a novel hydroboration/oxidation procedure, a deprotection/transannular Mannich reaction, and as a highlight, a tandem catalysis cascade combining an enynene ring-closing metathesis and a selective hydrogenation.",10.1021/ja107533m,2010-09-24,0.6211940493468011
Synlett,Concise Two-Step Synthesis of γ-Pyrone from Acetone,"γ-Pyrone (1) is readily accessible in 59% overall yield via 1,1,5,5-tetraethoxy-3-pentanone (10b) and subsequent acidic hydrolysis. The synthesis enables an easy scale up, as demonstrated for intermediate 10b.",10.1055/s-2004-835620,2004-10-20,0.6211849654527782
Organic Letters,Total Syntheses of Graphisin A and Sydowinin B,"Efficient syntheses of the highly substituted benzophenone graphisin A and the xanthone sydowinin B are described. Key steps involve aryl anion addition to substituted benzaldehyde derivatives, subsequent methyl ester installation, and dehydrative cyclization. Oxidation of graphisin A led to a spirodienone derived from a highly substituted benzoquinone intermediate.",10.1021/ol301107m,2012-05-23,0.6211839983257632
Tetrahedron,Synthesis of large ring proton cryptate tridecalino [2.2.2] cryptand⊃2hI,,10.1016/s0040-4039(00)84557-8,1986-01-01,0.6211643939590771
Organic Letters,"An Efficient Route to 4-Aryl-5-pyrimidinylimidazoles via Sequential Functionalization of 2,4-Dichloropyrimidine","[reaction: see text] Starting from 2,4-dichloropyrimidine, a concise synthetic route to medicinally important 4-aryl-5-pyrimidinylimidazoles is described. Sequential substitution of the 4- and 2-chloro groups using a regioselective Sonogashira coupling, followed by nucleophilic substitution, led to pyrimidinylalkyne derivatives, which were then oxidized to their corresponding 1,2-diketones. These 1,2-diketones, on cyclocondensation with ammonium acetate and an aldehyde, furnished the desired pyrimidinyl imidazoles in good overall yields.",10.1021/ol052663x,2005-12-30,0.6211561319059504
Journal of Organic Chemistry,Enantioselective Synthesis of the Antiinflammatory Agent (−)-Acanthoic Acid,"An enantioselective synthesis of the potent antiinflammatory agent (-)-acanthoic acid (1) is described. The successful strategy departs from (-)-Wieland-Miescher ketone (10), which is readily available in both enantiomeric forms and constitutes the starting point toward a fully functionalized AB ring system of 1. Conditions were developed for a regioselective double alkylation at the C4 center of the A ring, which produced compound 32 as a single stereoisomer. Construction of the C ring of 1 was accomplished via a Diels-Alder reaction between sulfur-containing diene 43 and methacrolein (36), which after desulfurization and further functionalization yielded synthetic acanthoic acid. The described synthesis confirms the proposed stereochemistry of the natural product and represents a fully stereocontrolled entry into an underexplored class of biologically active diterpenes.",10.1021/jo0159035,2001-11-22,0.6211472622666561
Journal of Organic Chemistry,New Modular and Efficient Approach to 6-Substituted Pyridin-2-yl C-Nucleosides,"A novel modular, efficient, and practical methodology of preparation of 6-substituted pyridin-2-yl C-nucleosides was developed. An addition of 2-lithio-6-bromopyridine 2b to TBDMS-protected 2-deoxyribonolactone 5 gave aduct 7 as an equilibrium mixture of anomeric hemiketals 1-(6-bromopyridin-2-yl)-1-hydroxynucleosides 7a,b and its open form 7c. Reduction of the adduct 7 with Et3SiH and BF3 x Et2O afforded the desired 6-bromonucleoside 8a as pure beta-anomer in a total yield of 32% over two steps from 5. Intermediate 8a was then subjected to a series of palladium catalyzed cross-coupling reactions and aminations to give a series of protected 1beta-(6-alkyl-, 6-aryl-, and 6-aminopyridin-2-yl)-2-deoxyribonucleosides 9. Catalytic hydrogenation of 8a gave an unsubstituted pyridine C-nucleoside, and diazotative oxodeamination of 6-aminopyridine nucleoside 9f by isopentyl nitrite in acetic acid gave 6-oxopyridine nucleoside 10i. Deprotection of silylated nucleosides 9 by Et3N.3HF gave a series of free C-nucleosides 10.",10.1021/jo061080d,2006-08-22,0.6211425196757281
Tetrahedron,Practical synthesis of (E)- and (Z)-2-silyl-3-penten-1-ols with high enantiopurity,,10.1016/j.tetlet.2010.06.104,2010-06-26,0.6211395871494241
Organic Letters,Application of Intramolecular Enyne Metathesis to the Synthesis of Aza[4.2.1]bicyclics:  Enantiospecific Total Synthesis of (+)-Anatoxin-a,"A concise synthesis of the potent nAChR agonist (+)-anatoxin-a (1) has been completed in a series of only nine chemical operations and 27% overall yield from commercially available D-methyl pyroglutamate (4). The synthesis features a novel procedure for the diastereoselective preparation of cis-2,5-disubstituted pyrrolidines leading to 10, which underwent an intramolecular enyne metathesis to afford a bridged azabicyclic intermediate that was transformed into 1. [reaction: see text]",10.1021/ol049631e,2004-03-23,0.621128365613602
Tetrahedron,"7-Vinyldecyl acetate, novel inhibitor of pheromonal attraction in the false codling moth, cryptophlebia leucotreta",,10.1016/s0040-4039(00)97954-1,1990-01-01,0.6211237276659695
Journal of Organic Chemistry,"Synthetic Transformation of Ptychantin into Forskolin and 1,9-Dideoxyforskolin","Forskolin (1), a highly oxygenated labdane diterpenoid and an activator of adenylate cyclase, has been synthesized in 12 steps and 12% overall yield from ptychantin A (4), which has been isolated from liverwort Ptychanthus striatus in good yield. The 1alpha-hydroxy group was furnished by stereoselective reduction of the corresponding carbonyl group by sodium in t-BuOH. The 9alpha-hydroxy group was introduced stereoselectively by epoxidation of delta(9.11)-enolether. 1,9-Dideoxyforskolin (2), an inhibitor of glucose transporter, has been synthesized in 8 steps and 37% overall yield. The hydroxy group at C-1 was removed by solid-state thicarbonylimidazolation and subsequent radical cleavage.",10.1021/jo060477e,2006-05-13,0.6211158358108582
Organic Letters,Formal Total Synthesis of <i>N</i>-Methylmaysenine,"A novel synthetic approach for the formal total synthesis of N-methylmaysenine (1) has been developed. Key steps involve the Ti-mediated vinylogous Mukaiyama aldol reaction of chiral ketene silyl N,O-acetal with beta-dithiane-substituted aldehyde, an aldol condensation, and a ring-closing metathesis reaction.",10.1021/ol900384u,2009-03-18,0.6211061191870425
Journal of Organic Chemistry,Stereocontrolled Total Synthesis of (−)-Kaitocephalin,"This paper describes the successful implementation of a stereocontrolled strategy for the total chemical synthesis of the pyrrolidine-based alkaloid (--)-kaitocephalin. This scalable synthetic route profits from the strategic utilization of substrate-controlled manipulations for the iterative installation of the requisite stereogenic centers. The key transformations include a diastereoselective modified Claisen condensation, a chemo- and diastereoselective reduction of a beta-keto ester, and the substrate-directed hydrogenation of a dehydroamino ester derivative. During the course of our investigations, an interesting stereoconvergent cyclization reaction was discovered for the efficient assembly of the kaitocephalin 2,2,5-trisubstituted pyrrolidine core.",10.1021/jo702329z,2008-01-29,0.6210991541428398
Tetrahedron,A new synthetic route for the γ-lactone precursors of hydroxyethylene dipeptide isosteres,,10.1016/s0040-4039(00)73819-6,1993-09-01,0.6210914970522365
Organic Letters,"Synthetic Studies on Et-743. Asymmetric, Stereocontrolled Construction of the Tetrahydroisoquinoline Core via Radical Cyclization on a Glyoxalimine",[Structure: see text] The asymmetric synthesis of a highly functionalized tetrahydroisoquinoline relevant to the total synthesis of Et-743 is described. The key step involves a highly diastereoselective radical cyclization on a glyoxalimine derivative.,10.1021/ol061192r,2006-06-22,0.6210912981889527
Journal of Organic Chemistry,Applications and Limitations of the I<sub>2</sub>-Mediated Carbamate Annulation for the Synthesis of Piperidines: Five- versus Six-Membered Ring Formation,"A protecting-group-free synthetic strategy for the synthesis of piperidines has been explored. Key in the synthesis is an I2-mediated carbamate annulation, which allows for the cyclization of hydroxy-substituted alkenylamines into piperidines, pyrrolidines, and furans. In this work, four chiral scaffolds were compared and contrasted, and it was observed that with both d-galactose and 2-deoxy-d-galactose as starting materials, the transformations into the piperidines 1-deoxygalactonorjirimycin (DGJ) and 4-epi-fagomine, respectively, could be achieved in few steps and good overall yields. When d-glucose was used as a starting material, only the furan product was formed, whereas the use of 2-deoxy-d-glucose resulted in reduced chemo- and stereoselectivity and the formation of four products. A mechanistic explanation for the formation of each annulation product could be provided, which has improved our understanding of the scope and limitations of the carbamate annulation for piperidine synthesis.",10.1021/jo401512h,2013-08-29,0.6210872268118032
Organic Letters,Total Synthesis of (−)-Geissoschizol through Ir-Catalyzed Allylic Amidation as the Key Step,"promoted asymmetric allylic amidation of a secondary alcohol derived from tryptamine has been utilized to forge a tetrahydro-β-carboline. Based on this key step, a novel, facile, and enantioselective total synthesis of (-)-geissoschizol was achieved in 10 steps.",10.1021/acs.orglett.7b03133,2017-11-02,0.6210801718358108
Journal of Organic Chemistry,Synthesis of the Adrenergic Bronchodilators (<i>R</i>)-Terbutaline and (<i>R</i>)-Salbutamol from (<i>R</i>)-Cyanohydrins<sup>1</sup>,"Stereoselective syntheses of ( R )-terbutaline and ( R )-salbutamol acetal, which are important bronchodilators, starting from O-protected ( R )-cyanohydrins are described. ( R )-Terbutaline hydrochloride ( R )- 9 ·HCl is obtained in an overall yield of 44% with >98% ee from the O-bisallyl-protected cyanohydrin ( R )- 4k via a Ritter N-tertiary butylation to the amide ( R )- 6a, hydrogenation to the amino alcohol ( R )- 7a, and deprotection of the hydroxyl functions. ( R )-Salbutamol acetals ( R )- 7b, c can be obtained from the corresponding O-protected ( R )-cyanohydrins either via the route described for ( R )-terbutaline or via selective hydrogenation of the protected cyanohydrin ( R )- 11 to the imino derivative, transimination with tert -butylamine, followed by hydrogenation with NaBH 4 to give the 2-amino alcohol derivative ( R )- 12 . Desilylation of ( R )- 12 to ( R )- 7c is performed with LiAlH 4 . Hydrolytic cleavage of the acetals ( R )- 7b and c to ( R )-salbutamol was not yet possible without racemization.",10.1021/jo970032d,1997-06-13,0.6210692115203924
Tetrahedron,Development of an approach to the synthesis of the plakortones,,10.1016/s0040-4039(00)00464-0,2000-05-01,0.621063227919723
Organic Process Research & Development,Process Development and Scale-up of a Selective α<sub>1</sub>-Adrenoceptor Antagonist,A synthetic route to a potent and selective α-1-adrenergic receptor antagonist has been developed and demonstrated in a pilot plant. The route has been used in two pilot plant campaigns and has produced RO3203546 in 2.3 and 12.0 kg batch sizes. The first pilot plant campaign focused primarily on the end-game of the process with particular emphasis on the development of a method to isolate the active pharmaceutical ingredient (API). The second pilot plant campaign allowed front-end process improvements to be demonstrated. The reiterative process improvements resulted in an economical process with improved throughput and product quality when compared to the original discovery synthesis.,10.1021/op0498114,2004-12-18,0.6210625246975676
Journal of the American Chemical Society,Total Synthesis of (+)-Rishirilide B:  Development and Application of General Processes for Enantioselective Oxidative Dearomatization of Resorcinol Derivatives,"A concise synthesis of (+)-rishirilide B (2) is described. This is the first synthesis to be reported for the (+)-enantiomer of rishirilide B (2) as found in nature. The strategy accentuates the valuable combination of a method for o-quinone methide coupling with a method for enantioselective resorcinol dearomatization, which provides a densely functionalized chiral building block. The convergent synthesis illustrates several improvements and refinements to these methods and their supporting chemistries. Among these is the in situ generation of PhI[OTMS]OTf. Combination of this oxidant with phenol 31 constitutes the first example of a diastereoselective oxidative dearomatization of a resorcinol displaying a 2-alkyl substituent. In addition, the preparation of the cyclic sulfone 34 is reported. As a new dimethide precursor expressing a readily cleavable O-benzyl residue, sulfone 34 should prove useful in future endeavors. A protocol using the aluminum amide of dimethylhydrazine for opening and cleavage of a [1,4]-dioxan-2-one is also described. This procedure unmasks the hydroxy dione 36 by jettisoning the chiral directing group. Regioselective O-carbamylation of the 1,3-dione 36 enables the transformation of the remaining carbonyl into the alpha-hydroxy carboxylic acid found in 2. The total synthesis of (+)-rishirilide B (2) requires 15 pots from benzaldehyde 17 and 13 pots from benzaldehyde 32. The final product emerges in yields of 12.5% and 20.3% from compounds 17 and 32, respectively. The longest linear sequence requires eight chromatographies. Important observations leading to the development of the principle asymmetric method are described within the context of the total synthesis.",10.1021/ja062987w,2006-11-16,0.621062503403231
Organic Letters,Enantioselective Deprotonation of <i>m</i><i>eso</i>-Cycloheptanone Derivative:  Application to the Synthesis of a Potential Intermediate for Pseudomonic Acid B,"[reaction: see text] A novel synthetic path to a potential intermediate for the synthesis of pseudomonic acid B was established by employing enantioselective deprotonation of a meso-cycloheptanone derivative bearing hydroxy groups at the 3,4,5,6-positions with lithium (S,S')-alpha,alpha'-dimethyldibenzylamide as a key step.",10.1021/ol027192i,2002-11-15,0.6210527114353364
Organic Letters,Rhodium-Catalyzed Coupling–Cyclization of Alkenyldiazoacetates with <i>o</i>-Alkenyl Arylisocyanides: A General Route to Carbazoles,"A rhodium-catalyzed coupling-cyclization reaction of alkenyldiazoacetates with o-alkenyl arylisocyanides has been developed. In this reaction, the highly reactive alkenylketenimine intermediates generated by coupling reaction of alkenyldiazoacetates with o-alkenyl arylisocyanides undergo intramolecular [4 + 2] cycloaddition and provide a novel, highly efficient method for the one-step synthesis of carbazoles by formation of three new bonds and two rings from readily available acyclic starting materials.",10.1021/acs.orglett.9b00307,2019-03-22,0.6210524174610693
Journal of Organic Chemistry,Interrupting Base-Mediated Benzofuran Ring Transformation with Michael Acceptors,"A simple two-stage approach for the synthesis of 3-(2-arylbenzofuran-3-yl)propanoates and propanamides has been developed employing simple acrylates and acrylamides and readily available 3-aroylbenzofurans. The key step of this process involves a base-mediated ring opening of the 3-aroylbenzofurans and subsequent Michael addition of the resulting 1,3-dicarbonyl intermediate with acrylate/acrylamide, followed by the deformylation in one-pot. The resulting products undergo an acid-mediated dehydrative cyclization to arrive at these targets.",10.1021/acs.joc.7b01267,2017-08-18,0.6210486358714861
Journal of Organic Chemistry,Enantioselective Synthesis of 12-Amino Alkylidenecyclopentenone Prostaglandins,"An enantioselective synthesis of new 12-amino alkylidenecyclopentenone prostaglandins is reported. The key step of the synthesis involved a [3.3] sigmatropic rearrangement of an asymmetric allylic cyanate to elaborate an asymmetric 5-amino-1,6-diene which was further transformed into cyclopentenone by successive ring-closing metathesis reaction catalyzed by the Grubbs reagent and one-pot oxidation. A palladium-catalyzed cross-coupling reaction on a 5-iodo-1,5-diene allowed the synthesis of prostanoids with variable Rw side chains. These new compounds exhibit high cytotoxic activities.",10.1021/jo010481k,2002-05-31,0.6210457294877277
Journal of Organic Chemistry,Efficient Asymmetric Synthesis of Biologically Important Tryptophan Analogues via a Palladium-Mediated Heteroannulation Reaction,"A novel and concise synthesis of optically active tryptophan derivatives was developed via a palladium-catalyzed heteroannulation reaction of substituted o-iodoanilines with an internal alkyne. The required internal alkyne 14a or 25 was prepared in greater than 96% de via alkylation of the Schöllkopf chiral auxiliary 19 employing diphenyl phosphate as the leaving group. The Schöllkopf chiral auxiliary was chosen here for the preparation of L-tryptophans would be available from D-valine while the D-isomers required for natural product total synthesis would originate from the inexpensive L-valine (300-g scale). Applications of the palladium-catalyzed heteroannulation reaction were extended to the first asymmetric synthesis of L-isotryptophan 38 and L-benz[f]tryptophan 39. More importantly, the optically pure 6-methoxy-D-tryptophan 62 was prepared by this protocol on a large scale (>300 g). This should permit entry into many ring-A oxygenated indole alkaloids when coupled with the asymmetric Pictet-Spengler reaction. In addition, an improved total synthesis of tryprostatin A (9a) was accomplished in 43% overall yield employing this palladium-mediated process.",10.1021/jo001679s,2001-06-01,0.6210282082180668
Tetrahedron,The phosphazo route to 2-alkenamides from acrylic acid and its derivatives,,10.1016/s0040-4039(00)88859-0,1990-01-01,0.6210263009189836
Synthesis,Synthesis of (+)-Harmicine,"A facile convergent access to the important indole alkaloid (+)-harmicine is described, starting from tryptamine and ( R )-acetoxysuccinic anhydride via the corresponding acetoxysuccinimide in very good overall yield. Regioselective reduction of an unsymmetrical imide carbonyl group and acid-catalyzed stereoselective intramolecular cyclization were the key features involved. The directing group to induce asymmetry was finally detached via the corresponding iodide by using tributyltin hydride chemistry.",10.1055/s-0034-1378381,2014-07-11,0.6210175552650796
Synlett,A Concise Total Synthesis of the Purported Structure of Flossonol,We report the first total synthesis of flossonol in only five steps and of one of its isomers in seven steps using a radical ­addition/cyclization sequence as the key step. Comparison of our spectroscopic data with those of the literature indicates a misassignment in the structure of flossonol.,10.1055/s-0032-1317848,2012-12-21,0.6210118979672882
Journal of the American Chemical Society,"Microbial Synthesis of the Energetic Material Precursor 1,2,4-Butanetriol","The lack of a route to precursor 1,2,4-butanetriol that is amenable to large-scale synthesis has impeded substitution of 1,2,4-butanetriol trinitrate for nitroglycerin. To identify an alternative to the current commercial synthesis of racemic d,l-1,2,4-butanetriol involving NaBH4 reduction of esterified d,l-malic acid, microbial syntheses of d- and l-1,2,4-butanetriol have been established. These microbial syntheses rely on the creation of biosynthetic pathways that do not exist in nature. Oxidation of d-xylose by Pseudomonas fragi provides d-xylonic acid in 70% yield. Escherichia coli DH5alpha/pWN6.186A then catalyzes the conversion of d-xylonic acid into d-1,2,4-butanetriol in 25% yield. P. fragi is also used to oxidize l-arabinose to a mixture of l-arabino-1,4-lactone and l-arabinonic acid in 54% overall yield. After hydrolysis of the lactone, l-arabinonic acid is converted to l-1,2,4-butanetriol in 35% yield using E. coli BL21(DE3)/pWN6.222A. As a catalytic route to 1,2,4-butanetriol, microbial synthesis avoids the high H2 pressures and elevated temperatures required by catalytic hydrogenation of malic acid.",10.1021/ja036391+,2003-10-01,0.6209959798673385
Tetrahedron,"Asymmetric synthesis of (2S,3S)-3-hydroxy-2-phenylpiperidine via ring expansion",,10.1016/s0040-4039(01)01223-0,2001-09-01,0.6209871607506605
European Journal of Organic Chemistry,"Stereodivergent Syntheses of <i>altro</i> and <i>manno</i> Stereoisomers of 2‐Acetamido‐1,2‐dideoxynojirimycin","A stereoselective synthesis of 2‐acetamido‐1,2‐dideoxyaltronojirimycin ( 8 ) and its manno epimer 9 is described. The synthetic approach is based on key bicyclic carbamate 7 , which is easily accessible with high enantiomeric purity on a multigram scale by Sharpless asymmetric epoxidation of 1,4‐pentadien‐3‐ol or 2,4‐pentadien‐1‐ol. This procedure completes an efficient stereodivergent approach to five isomers of 2‐acetamido‐1,2‐dideoxyiminosugars in high overall yields starting from the same key intermediate 7 . The approach described in this paper is based on control of the stereoselectivity of the sulfite ring‐opening reaction to give retention of configuration through anchimeric assistance from the endocyclic amine.",10.1002/ejoc.201701282,2017-12-21,0.6209753288736941
Journal of Organic Chemistry,Total Synthesis of the Proposed Structure of Uncarialin A,"High Resolution Image Download MS PowerPoint Slide The stereoselective total synthesis of the proposed structure of a potent serotonin 5-HT 1A receptor agonist uncarialin A ( 1 ) is described. By employing the readily available meroquinene tert -butyl ester as the chiral synthon, the target structure has been prepared in a six-step linear sequence with a 17% overall yield. In comparison to the sample isolated from natural sources, the synthetic product shows significant spectral differences, strongly suggesting that the structure of the natural product should be revised.",10.1021/acs.joc.1c00324,2021-04-21,0.6209737673685785
Journal of Organic Chemistry,"Total Syntheses and Absolute Stereochemical Correction of Negundin B, Vitexin 1, and Vitexin 6","A highly adaptable asymmetric synthetic route toward dihydronaphthalene lignans was developed, with its application to the syntheses of negundin B and vitexin 1/6 described herein. This developed pathway proceeded through an enantioselective aldol reaction to establish the contiguous stereocenters present in the final structures with subsequent functional group transformations yielding (-)-negundin B and (-)-vitexin 1/6. The enantioselective synthesis of vitexin 1/6 allowed the correction of absolute configuration, which has been widely incorrectly reported.",10.1021/acs.joc.3c02751,2024-02-20,0.6209622001115587
Organic Letters,A Concise Synthesis of a β-Lactamase Inhibitor,MK-7655 (1) is a β-lactamase inhibitor in clinical trials as a combination therapy for the treatment of bacterial infection resistant to β-lactam antibiotics. Its unusual structural challenges have inspired a rapid synthesis featuring an iridium-catalyzed N-H insertion and a series of late stage transformations designed around the reactivity of the labile bicyclo[3.2.1]urea at the core of the target.,10.1021/ol202195n,2011-09-15,0.6209532830938741
Tetrahedron,The first total synthesis of potent human chymase inhibitor SPF32629B via regioselective bromination and O-acylation strategy,,10.1016/j.tetlet.2010.03.091,2010-03-26,0.6209526080203799
European Journal of Organic Chemistry,"Total Synthesis of the Spirocyclic Oxindole Alkaloids Corynoxine, Corynoxine B, Corynoxeine, and Rhynchophylline","Abstract Racemic total syntheses of four spirocyclic oxindole alkaloids are reported. The general starting material was an N ‐2‐butenylated 2‐hydroxytryptamine, which underwent a base‐mediated Mannich spirocyclisation with a functionalised aldehyde to generate the C‐ring. The second key step was a Pd‐catalysed cyclisation of an α‐keto ester enolate (in the original aldehyde) onto an allylic carbonate (in the N ‐substituent) to form the D‐ring. The stereoselectivities of the key steps were moderate, but the isomers were readily purified, so that the natural products could be conveniently prepared, three of them for the first time.",10.1002/ejoc.201201505,2013-01-07,0.6209482031338246
Tetrahedron,A new synthesis of 1- and 2-amino phenazines,,10.1016/s0040-4039(01)82729-5,1959-01-01,0.6209477913395979
Tetrahedron,A new synthesis of 3-amino-2-alkenoates,,10.1016/s0040-4039(00)87168-3,1982-01-01,0.6209477913395979
Journal of the American Chemical Society,"Asymmetric Synthesis of Cyclopamine, a Hedgehog (Hh) Signaling Pathway Inhibitor","Cyclopamine is a teratogenic steroidal alkaloid, which inhibits the Hedgehog (Hh) signaling pathway by targeting the Smoothened (Smo) receptor. Suppression of Hh signaling with synthetic small molecules has been pursued as a therapeutic approach for the treatment of cancer. We report herein the asymmetric synthesis of cyclopamine based on a two-stage relay strategy. Stage-I: total synthesis of veratramine through a convergent approach, wherein a crucial photoinduced excited-state Nazarov reaction was applied to construct the basic [6–6–5–6] skeleton of C- nor -D- homo -steroid. Stage-II: conversion of veratramine to cyclopamine was achieved through a sequence of chemo- selective redox manipulations.",10.1021/jacs.3c10362,2023-11-10,0.6209418923083363
Synlett,"Multigram-Scale Synthesis of a gem-Difluoro-Substituted 4,5,6,7-Tetrahydrobenzo[c]thiophen-4-one Heterocycle via Oxidative Chlorination and Radical Smiles Rearrangement","Abstract We report an optimized synthetic route towards a functionalized 4,5,6,7-tetrahydrobenzo[c]thiophene heterocycle bearing a gem-difluoromethylene moiety in 4 steps with an overall yield of 43%. The CF2 fragment was incorporated using a building block approach, by coupling an appropriate fluorinated alcohol with a C-3 sulfonyl chloride, synthesized via oxidative chlorination of an exocyclic benzyl thioether. Visible-light-mediated Smiles rearrangement of the resulting fluorosulfonate ester then furnishes the desired fluorinated thiophene scaffold.",10.1055/a-2153-7341,2023-08-14,0.620937303874131
Journal of the American Chemical Society,A Reverse Approach to the Total Synthesis of Halichondrin B,"A new strategy is described for the total synthesis of halichondrin B featuring reversal of the sequential construction of a number of its cyclic ethers from the classical approach by instead forming C–O bonds first followed by C–C bond formation. Employing the Nicholas reaction to generate linear ethers as precursors for the total synthesis of halichondrin B and other members of the halichondrin and eribulin families of compounds, this novel approach provides new opportunities for the development of improved syntheses of these complex and valuable compounds. In this Article, we report the syntheses of defined fragments I, MN, EFG, and A . Fragments I and MN were then coupled and elaborated to advanced intermediate IJKLMN, which was joined with fragment EFG to afford, after appropriate elaboration and macrolactonization, the more advanced polycyclic intermediate EFGHIJKLMN . Elaboration of the latter and coupling with fragment A followed by further functionalization completed the total synthesis of halichondrin B through a short and convergent pathway.",10.1021/jacs.1c05270,2021-06-09,0.6209230171957305
Organic Letters,Asymmetric Synthesis of the Fully Elaborated Pyrrolidinone Core of Oxazolomycin A,"The asymmetric synthesis of the key pyrrolidinone core, including a highly elaborated exocyclic carbon chain, of the γ-lactam β-lactone antibiotic oxazolomycin A is described. Principal features include the Birch reduction of an aromatic pyrrole nucleus, a late stage RuO(4) catalyzed pyrrolidine oxidation, and a highly diastereoselective organocerium addition to an aldehyde.",10.1021/ol302541j,2012-10-12,0.6209228929196768
Organic Letters,Synthetic Progress toward Azadirachtins. 1. Enantio- and Diastereoselective Synthesis of the Left-Wing Fragment of 11-<i>epi</i>-Azadirachtin I,"A highly enantio- and diastereoselective synthesis of the left-wing fragment of 11-epi-azadirachtin I characterized with the pairwise use of palladium- and gold-catalyzed cascade reactions is presented. By enlisting a sequence of stereocontrolled transformations, our 21-step route established the stereocenters of the left-wing fragment from one chiral starting material, (-)-carvone, which would significantly facilitate the synthetic studies of the azadirachtin-type limonoids.",10.1021/acs.orglett.5b00829,2015-04-28,0.6209218951751008
Tetrahedron,"An improved preparation of 3-α-acetoxy-11,20-diketo-(5β)-pregnane, the key intermediate in the synthesis of 11-oxygenated corticosteroids.",,10.1016/s0040-4039(01)89606-4,1967-01-01,0.6209101833724544
Tetrahedron,The synthesis of a key intermediate en route to gelsemine: a program based on intramolecular displacement of the carbonoxygen bond of a strategic oxetane,,10.1016/s0040-4039(01)02212-2,2002-01-01,0.6209089772063571
Synlett,Synthesis of a Highly Selective EP2-Receptor Agonist,"A practical method for the synthesis of the prostanoid EP2-receptor agonist 1 was developed. This method includes magnesium-mediated Julia olefination of aldehyde 2 with the optically active sulfone 3, which was prepared from allylic alcohol 4 using the Sharpless asymmetric epoxidation procedure.",10.1055/s-2002-19781,2002-01-01,0.6209061794149037
Organic Letters,Enantioselective Formal Total Synthesis of (+)-Aspergillide C,"An enantioselective formal total synthesis of the cytotoxic macrolide (+)-aspergillide C has been accomplished from (S)-(-)-glyceraldehyde acetonide and the Danishefsky-Kitahara diene. Strategic transformations include a hetero Diels-Alder reaction, Ferrier-type addition, and palladium-catalyzed oxidative lactonization to set key stereocenters within the dihydropyran core, followed by fragment coupling via (E)-selective Julia-Kocienski olefination.",10.1021/ol902154p,2009-10-09,0.6209046666573897
Organic Letters,"Facile Route to 3,5-Disubstituted Morpholines:  Enantioselective Synthesis of O-Protected <i>trans</i>-3,5-Bis(hydroxymethyl)morpholines","[reaction: see text] (3R,5R)-1 R1 & R2 = TBDPS, (3S,5R)-2 R1 = Bn,R2 = TBDPS, (3S,5S)-3 R2 & R2 = Bn. trans-3,5-Bis(benzyl/tert-butyldiphenylsilyloxymethyl)morpholines, promising candidates for the C(2)-symmetric class of chiral reagents, were prepared with excellent optical purity. A key step in the synthesis is the coupling of a serinol derivative with 2,3-O-isopropylideneglycerol triflate or its equivalent. This methodology was extended to the synthesis of chiral trans-3-(benzyloxymethyl)-5-(tert-butyldiphenylsilyloxymethyl)morpholine, a potentially useful chiral building block.",10.1021/ol035998s,2003-12-10,0.6209000705350767
Angewandte Chemie International Edition,Short Chemoenzymatic Total Synthesis of <i>ent</i>‐Hydromorphone: An Oxidative Dearomatization/Intramolecular [4+2] Cycloaddition/Amination Sequence,"A short synthesis of ent-hydromorphone has been achieved in twelve steps from β-bromoethylbenzene. The key transformations involved the enzymatic dihydroxylation of the arene to the corresponding cis-dihydrodiol, Mitsunobu coupling with the ring A fragment, oxidative dearomatization of the C3 phenol, and the subsequent [4+2] cycloaddition to form ring B of the morphinan. The synthesis was completed by intramolecular amination at C9.",10.1002/anie.201400286,2014-03-18,0.6208956267369579
Organic Process Research & Development,"Development of Synthetic Routes, via a Tropinone Intermediate, to a Long-Acting Muscarinic Antagonist for the Treatment of Respiratory Disease","This contribution describes the development of two synthetic routes to an investigational muscarinic antagonist for the treatment of chronic obstructive pulmonary disease. The first route used a starting material which was in plentiful supply within the GSK network and was used to make material for early clinical trials and safety assessment studies. Further investigations identified a second, potential long-term manufacturing route from commercially available building blocks, using substrate control to install the two stereocentres with excellent selectivity. A key step was a substrate-directed epoxide reduction which also gave rise to a minor byproduct through a skeletal rearrangement of the tropane ring. A deuterium-labeling experiment was carried out, which shed light on the origin of the byproduct, and also guided the improvement of reaction conditions.",10.1021/op3002933,2013-03-07,0.6208950920278692
Journal of Organic Chemistry,Stereoselective Synthesis of Hydrindane and Hydroazulene Derivatives by Transannular Cyclization of Nine- and Ten-Membered Carbocycles,"Treatment of cis -fused bicyclic diene dicarboxylates with Li/naphthalene triggers a tandem ring-opening and transannular cyclization process that stereoselectively yields hydroazulenes and hydrindanes derivatives. Cyclononadienyl diesters, which can be isolated after the ring-opening step by judicious choice of the reaction conditions, undergo a tandem conjugate addition/intramolecular Michael addition upon treatment with chiral lithium amides to give bicyclic β-amino esters in a process where 4 contiguous stereocenters are formed with high diastereocontrol. A concise route toward the highly enantioenriched AEF ring core of the aconitine-type alkaloids has been developed as an application of this methodology. The starting cis -fused bicyclic dicarboxylates are easily prepared in one step by reductive alkylation of diisopropyl phthalate (Na/THF, followed by the appropriate bis -electrophiles).",10.1021/acs.joc.1c01751,2021-09-14,0.6208758620121149
Journal of Organic Chemistry,"Synthesis of 2-Phenyl-4,5-Substituted Oxazoles by Copper-Catalyzed Intramolecular Cyclization of Functionalized Enamides","An efficient two-step synthesis of 2-phenyl-4,5-substituted oxazoles involving intramolecular copper-catalyzed cyclization of highly functionalized novel β-(methylthio)enamides as the key step has been reported. These enamides are obtained by nucleophilic ring-opening of newly synthesized 4-[(methylthio)hetero(aryl)methylene]-2-phenyl-5-oxazolone precursors by alkoxides, amines, amino acid esters and aryl/alkyl Grignard reagents, thus leading to the introduction of an ester, N-substituted carboxamide or acyl functionalities at 4-position of the product oxazoles. Synthesis of two naturally occurring 2,5-diaryloxazoles, i.e., texamine and uguenenazole, via two-step hydrolysis-decarboxylation of the corresponding 2,5-diaryloxazole-4-carboxylates has also been described. Similarly, three of the serine-derived oxazole-4-carboxamides were elaborated to novel trisubstituted 4,2'-bisoxazoles through DAST/DBU-mediated cyclodehydration-dehydrohalogenation sequence. The present protocol is complementary and an improvement to our previously reported silver carbonate-induced cyclization of β-bis(methylthio)enamides to 2-phenyl-5-(methylthio)-4-substituted oxazoles.",10.1021/jo3021192,2012-11-06,0.6208758459629977
Tetrahedron,A novel enantioselective synthesis of HMG Co-A reductase inhibitor NK-104 and a related compound,,10.1016/s0040-4039(00)60814-6,1992-01-01,0.6208724634166141
Organic Process Research & Development,"Preparation of the Key Intermediate in a Novel Synthesis of ZD9063P:  The Chemical Component of ADEPT, a Targeted Cytotoxic Therapy","A novel regioselective opening of the cyclic anhydride of a urethane derivative of glutamic acid using 4-(dimethylamino)pyridine (DMAP) as the catalyst has greatly simplified the synthesis of the target compound, ZD9063P, 5-( N -[( S )- N -{ N, N -bis(2-chloroethyl)amino}phenoxycarbonyl)-γ-glutamyl]amino)isophthalic acid.",10.1021/op000016+,2000-05-23,0.6208693561884607
Journal of Organic Chemistry,Formal Total Synthesis of (−)-Oseltamivir Phosphate,"An asymmetric synthesis of chiral intermediate 3 for (-)-oseltamivir phosphate has been accomplished from chiral building block 1, which was prepared by catalytic asymmetric synthesis.",10.1021/jo200698g,2011-05-31,0.6208367795500339
European Journal of Organic Chemistry,Concise Route to (–)‐ and (+)‐Aphanorphine,"Abstract This paper presents an application of two recently developed methodologies to the synthesis of naturally occurring (–)‐aphanorphine. The first method involves an indium‐mediated stereoselective α‐aminoallylation of aldehydes to prepare enantioenriched homoallylic amine derivatives. The second is the epoxidation and regioselective opening of the epoxide to afford 2‐substituted 3‐pyrrolidinols. The synthesis was completed by using a reported Friedel–Crafts alkylation and conventional functional‐group manipulation. According to the same route, the O ‐methyl derivative of unnatural (+)‐aphanorphine was prepared from ( S )‐2‐methylpropane‐2‐sulfinamide.",10.1002/ejoc.201100091,2011-02-23,0.6208339662908456
Tetrahedron,"A facile and rapid route for the synthesis of novel 1,5-substituted tetrazole hydantoins and thiohydantoins via a TMSN3-Ugi/RNCX cyclization",,10.1016/j.tetlet.2012.07.135,2012-08-07,0.6208294156819255
Tetrahedron,"Practical route for N,O-heteroatom interchange in 3,5-disubstituted-4-nitroisoxazoles",,10.1016/j.tetlet.2007.12.019,2007-12-10,0.6208260918325391
European Journal of Organic Chemistry,Total Synthesis of (–)‐C/D‐<i>cis</i>‐Dehydro‐3‐<i>O</i>‐methyl‐estradiols,"Abstract A convergent synthesis of (–)‐dehydro‐3‐ O ‐methyl‐C/D‐ cis ‐estradiol started from stereochemically defined substituted optically active 3‐(2‐arylethyl)‐γ‐butyrolactones. Regioselective bromination of the anisyl moiety, reductive ring opening of the iodolactone, and protecting‐group changes led to a Weinreb amide. This then underwent an intramolecular Grignard reaction closing the B‐ring to give a tetralone with defined configuration. Introduction of C‐11 through an allyl Grignard addition and subsequent ring‐closing metathesis gave a tetrahydro phenanthrene derivative. Oxidation of the side‐chain alcohol resulted in the key aldehyde group, and a final samarium‐diiodide‐mediated reductive D‐ring annulation resulted in the generation of the target dehydro‐C/D‐ cis ‐estradiol derivatives with high stereoselectivity. Structure elucidation was carried out using NOEDS (nuclear Overhauser enhanced differential spectroscopy) analysis on the one hand, and conversion into known 3‐ O ‐methyl‐13β‐estradiols by double‐bond hydrogenation on the other. Further efforts to use this estradiol synthetic strategy to generate more complex steroidal natural products and pharmaceutically interesting compounds are in progress.",10.1002/ejoc.201501341,2015-11-25,0.6208225922712144
Angewandte Chemie International Edition,Total Synthesis of (−)‐Daphenylline,"Total synthesis of (-)-daphenylline, a hexacyclic Daphniphyllum alkaloid, was achieved. Construction of the tricyclic DEF ring system was initiated by asymmetric Negishi coupling followed by an intramolecular Friedel-Crafts reaction. Installation of a side chain onto the tricyclic core was carried out through Sonogashira coupling, stereocontrolled Claisen rearrangement by taking advantage of the characteristic conformation of the tricyclic DEF core, and the stereoselective alkylation of a lactone. After the introduction of a glycine unit, the ABC ring system was stereoselectively constructed through intramolecular cycloaddition of the cyclic azomethine ylide.",10.1002/anie.201601958,2016-04-08,0.6207920958613147
Synlett,Concise Diverted Total Synthesis of Amphidinolide T1 and T4 from a (12E)-Cycloalkene by Selective Functionalization of the C12-C13 Double Bond,"Starting from a 19-membered (12E)-cycloalkene prepared by ring-closing metathesis, amphidinolide T1 and T4 were -efficiently synthesized via a short sequence of selective functionalization. The key steps highlighted stereoselective dihydroxylation of the (E)-C12-C13 double bond and highly regioselective silylation/desilylation of the (12S,13S)-diol. In particular, a significant solvent effect was discovered for suppressing 1,4 OO silyl migration or disilylation during selective mono-silylation of the (12R,13R)- and (12S,13S)-diols in toluene. In combination with our previous synthesis of amphidinolide T3, the same (12E)-cycloal-kene serves as an advanced common intermediate for concise diverted total synthesis of amphidinolide T family of marine macrolides.",10.1055/s-0031-1289903,2011-11-23,0.620790066125174
Tetrahedron,A novel one-pot synthesis of 2-benzoylpyrroles from benzaldehydes,,10.1016/j.tetlet.2010.02.054,2010-02-15,0.6207857128620322
Organic Letters,Enantioselective Synthesis of the Papulacandin Ring System:  Conversion of the Mannose Diastereoisomer into a Glucose Stereoisomer,"[structure] An enantioselective synthesis of three diastereoisomers of the C-arylglycoside tricyclic spiroketal nucleus of the papulacandins has been achieved, in which the initial asymmetry was introduced via a Sharpless dihydroxylation of substituted 5-aryl-2-vinylfurans. A selective oxidation-reduction sequence converted the mannose isomer into the glucose isomer. This sequence can conveniently produce both the papulacandin ring system along with its enantiomer and diastereomers in only 10-14 steps from 3,5-dimethoxybenzyl alcohol in 5-8% overall yield.",10.1021/ol006662a,2000-11-21,0.620771915224047
Synthesis,A Practical Synthesis of Indanofan via One-Pot Bromination of 3-Chloroethylbenzene,"All articles of this category A practical synthesis of Indanofan ( 1 ), a potent herbicide discovered by Mitsubishi Chemical Co. Ltd., was achieved starting from commercially available 3-chloroethylbenzene ( 2 ). 3-Chloro-α-bromostyrene ( 3 ), which was converted to 1-chloro-2-(3-chlorophenyl)prop-2-ene ( 5 ) in 2 steps, was synthesized via one-pot bromination of 2 . 2-Ethylindane-1,3-dione ( 6 ) was synthesized from ethyl butyrate and ethyl phthalate ( 11 ) using NaOEt. The coupling reaction of 5 with 6 followed by oxidation with AcOOH afforded 1 in a high overall yield. Indanofan - 3-chloro-α-bromostyrene - bromination - 3-chloroethylbenzene - 2-ethylindane-1,3-dione",10.1055/s-1999-3381,1999-02-01,0.6207622714077695
Chemical Science,A convergent total synthesis of ouabagenin,"A convergent total synthesis of ouabagenin, an aglycon of cardenolide glycoside ouabain, was achieved by assembly of the AB-ring, D-ring and butenolide moieties.",10.1039/c5sc00212e,2015-01-01,0.6207613673388338
Tetrahedron,Total synthesis of (±)-methyl 3-(3-isocyano-6-oxabicyclo[3.1.0]hex-2-en-5-yl)-2-propenoate,,10.1016/s0040-4039(01)82013-x,1981-01-01,0.6207611372366525
Synthesis,Synthesis of New Photoresponsive Stilbene Dendrons and Dendrimers,"A new convergent synthetic route for the synthesis of functionalized photoactive dendrimers having bis-stilbenoid skeletons on planar and tetrahedral cores, endowed with methoxy/methyl group has been developed. Optical spectroscopic techniques have been used to study absorption and emission properties and isomerization behavior of the stilbene dendrimers.",10.1055/s-2006-926401,2006-04-01,0.6207573193415222
Organic Letters,Synthetic Approach to the Natural <i>N</i>-Nitrosohydroxylamino Tetramic Acid JBIR-141,"An analogue of the Streptomyces metabolite JBIR-141, featuring a delicate N -nitrosohydroxylamine, a 3-acyltetramic acid, and an oxazoline, was synthesized by a convergent strategy from l -alanine, l -threonine, and l -glutamic acid. Key steps were the cyclization of an Ala–Thr derivative to give the oxazoline, a Dieckmann condensation affording the 3-acyltetramic acid, and the N -nitrosation of a hydroxylamino derivative of glutamic acid. An adequate protecting group strategy was established for coupling the three building blocks.",10.1021/acs.orglett.2c02006,2022-07-11,0.6207536493430128
European Journal of Organic Chemistry,Synthesis of Novel Cyclic Nitrones with <i>gem</i>‐Difluoroalkyl Side Chains Through Cascade Reactions,"New five‐membered cyclic nitrones with gem ‐difluoroalkyl groups in γ‐position have been prepared by a 3‐step sequence starting from propargylic alcohols. This domino process involves a base‐mediated isomerization reaction to enones, which are trapped in situ by nitroalkane anions. In a final step, starting from these key precursors, a reduction‐cyclization process affords the target molecules. Mono‐ and bicyclic nitrones have been prepared by this route which allows, as well, the synthesis of nitrones with functional groups in terminal position of the side chain.",10.1002/ejoc.202000972,2020-08-12,0.6206929132385836
Synthesis,A New Synthesis of Peptidyl Epoxysuccinates for Probing Cysteine Protease-Inhibitor P3/S3 Binding Interactions,All articles of this category peptidyl epoxysuccinates,10.1055/s-1999-3648,1999-08-01,0.6206903853956028
Journal of Organic Chemistry,Revisiting a Classic Approach to the <i>Aspidosperma</i> Alkaloids:  An Intramolecular Schmidt Reaction Mediated Synthesis of (+)-Aspidospermidine,"[reaction: see text] A total synthesis of (+)-aspidospermidine (1) is described. The key reactions used in the synthesis of this pentacyclic Aspidosperma alkaloid were a deracemizing imine alkylation/Robinson annulation sequence, a selective ""redox ketalization"", and an intramolecular Schmidt reaction. A Fischer indolization step carried out on a tricyclic ketone mirrored the sequence reported by Stork and Dolfini in their classic aspidospermine synthesis.",10.1021/jo051212n,2005-11-30,0.6206617466720717
Journal of Organic Chemistry,"Synthesis of Alstoscholarisines A–E, Monoterpene Indole Alkaloids with Modulating Effects on Neural Stem Cells","A divergent synthetic strategy has been developed for stereoselective total syntheses of alstoscholarisines A-E, monoterpenoid indole alkaloids which are modulators of adult neuronal stem cells. A pivotal step includes an intermolecular Michael addition of an indole-2-acetic acid methyl ester enolate to an α,β-unsaturated N-sulfonyllactam to form the C15, C16 bond of the alkaloids. Other features of the strategy involve a selective partial reduction of an intermediate N-sulfonyllactam followed by cyclization to a bridged aminal system that serves as a key precursor for all five of the alkaloids as well as the use of an allyl group as a masked aldehyde equivalent.",10.1021/acs.joc.8b00889,2018-05-07,0.6206587460432078
Angewandte Chemie International Edition,Total Synthesis of Ambruticin,Highly stereoselective radical cyclization and olefin metathesis reactions for the construction of oxacyclic building blocks were key steps in the convergent total synthesis of the orally active antifungal agent ambruticin (1).,10.1002/1521-3773(20020104)41:1<176::aid-anie176>3.0.co;2-#,2002-01-02,0.6206556769691018
Organic Letters,Total Synthesis of Acanthodoral Using a Rearrangement Strategy,"High Resolution Image Download MS PowerPoint Slide We present the second total synthesis of (±)-acanthodoral, a sesquiterpenoid derived from the marine nudibranch Acanthodoris nanaimoensis . Our approach involves a concise three-step transformation from a previously reported compound, resulting in the formation of a less strained precursor of the bicyclo[3.1.1]heptane core and both all-carbon quaternary stereocenters characteristic of the natural product. Notably, this synthetic route incorporates two pivotal steps: a Sm(II)-induced 1,2-rearrangement and a semipinacol rearrangement.",10.1021/acs.orglett.3c03717,2024-01-02,0.6206476774726596
Organic Letters,Total Synthesis of <i>cis</i>-Solamin:  Exploiting the RuO<sub>4</sub>-Catalyzed Oxidative Cyclization of Dienes,"[structure: see text] An enantioselective total synthesis of cis-solamin has been accomplished using a highly diastereoselective ruthenium tetroxide catalyzed oxidative cyclization as a crucial transformation. Further key steps involved an enzymatic desymmetrization, a TPAP-catalyzed oxidative termini differentiation, and a ruthenium-catalyzed Alder-ene reaction. Thus, the total synthesis of cis-solamin was achieved in 11 steps with an overall yield of 7.5%.",10.1021/ol060520k,2006-07-15,0.6206437707145288
Organic Letters,Enantioselective Construction of the ABCDE Pentacyclic Core of the <i>Strychnos</i> Alkaloids,"An efficient enantioselective 12-step synthesis of the ABCDE pentacyclic core of the Strychnos alkaloids is described. A key feature of this approach is an organocatalyzed enantioselective desymmetrization to generate the morphan core in high ee and dr. After palladium-catalyzed installation of the indole moiety, a subsequent 5-exo-trig dearomatizing atom transfer radical cyclization was developed to construct the C-ring. Following a series of functional group interconversions, the pentacyclic amine core was obtained with all the relevant architecture including five stereocenters pertaining to the Strychnos alkaloids.",10.1021/acs.orglett.7b00669,2017-03-30,0.6206313663301789
Organic Process Research & Development,"Optimization and Scale-Up Synthesis of a Lappaconitine Alkaloid Derivative, <b>QG3030</b>, as a Novel Osteoanabolic Agent","Our previous work revealed that the novel lappaconitine alkaloid derivative, QG3030 ( 6 ), has an enhanced osteogenesis effect in the ovariectomized rat model without acute oral toxicity. QG3030 ( 6 ) recently received approval for the Investigational New Drug application for its osteoporosis treatment from the Korean Ministry of Food and Drug Safety. Therefore, the need for an economical, large-scale production of QG3030 ( 6 ) motivated the development of a novel synthetic procedure for its clinical studies. We herein report an efficient, safe, and cost-effective synthesis of QG3030 ( 6 ) as a clinical candidate for osteoporosis treatment. As an optimized synthetic procedure, the reaction of lappaconitine·HBr ( 1 ·HBr, 1.0 kg scale) with co-oxidizing agents PhI(OAc) 2 -TEMPO (1.5 and 2 equiv) as a key step in a mixed EtOAc-acetone solution (v/v = 2/1) furnished α,β-unsaturated ketone ( 4 ), which was then treated with aq. NaOH to provide pure QG3030 ( 6, 352 g) in 58% overall yield with a purity of 99.8% after crystallization from EtOH–CH 2 Cl 2 . This pilot synthetic procedure was performed three times, and the reproducible results were obtained with both nearly identical yields and purities.",10.1021/acs.oprd.4c00344,2024-11-29,0.6206313276327007
Organic Letters,"Enantio- and Diastereoselective Synthesis of (<i>R</i>,<i>R</i>)-β-Methoxytyrosine","The nonproteinogenic amino acid (2R,3R)-beta-methoxytyrosine, a constituent of several cyclic depsipeptide natural products, was synthesized in protected form (8) from a readily available cinnamate ester in four steps and 62% overall yield with a greater than 28:1 er and 19:1 dr. This method provides a highly efficient, enantio- and diastereoselective synthesis of an important amino acid.",10.1021/ol071350u,2007-08-01,0.6206276921655997
Journal of Organic Chemistry,Collective Synthesis of <i>Lycopodium</i> Alkaloids and Tautomer Locking Strategy for the Total Synthesis of (−)-Lycojapodine A,"The collective total synthesis of Lycopodium alkaloids (+)-fawcettimine (1), (+)-fawcettidine (2), (+)-alopecuridine (4), (-)-lycojapodine A (6), and (-)-8-deoxyserratinine (7) has been accomplished from a common precursor (15) based on a highly concise route inspired by the proposed biosynthesis of the fawcettimine- and serratinine-type alkaloids. An intramolecular C-alkylation enabled efficient installation of the challenging spiro quaternary carbon center and the aza-cyclononane ring. The preparation of the tricyclic skeleton as well as the establishment of the correct relative stereochemistry of the oxa-quaternary center were achieved by hydroxyl-directed SmI(2)-mediated pinacol couplings. An unprecedented tandem transannular N-alkylation and removal of a Boc group was discovered to realize a biosynthesis-inspired process to furnish the desired tetracyclic skeleton. Of particular note is the unique and crucial tautomer locking strategy employed to complete the enantioselective total synthesis of (-)-lycojapodine A (6). The central step in this synthesis is the late-stage hypervalent iodine oxidant (IBX or Dess-Martin periodinane)/TFA-mediated tandem process, which constructed the previously unknown carbinolamine lactone motif and enabled a biomimetic transformation to generate (-)-lycojapodine A (6) in a single operation.",10.1021/jo3017555,2012-09-13,0.6206251858224469
Organic Process Research & Development,Stereoselective Synthesis of Monoamine Reuptake Inhibitor NS9544 Acetate,"(−)-3-(2-Benzothienyl)-8- H -8-azabicyclo[3,2,1]oct-2-ene acetate, NS9544 acetate, is a candidate drug intended to treat pain and other CNS disorders. In the synthetic route tropinone was enantioselective deprotonated with a chiral lithium amide derived from [ R -( R *, R *)]-bis(α-methylbenzyl)amine hydrochloride. The formed enolate was trapped as triflate and coupled with benzo[ b ]thiophene-2-boronic acid under Suzuki conditions. To further enhance the enantiomeric purity crystallisation with l -(+)-tartaric acid was performed. Finally N -demethylation with trichloroethylchloroformate followed by treatment with acetic acid afforded NS9544 as the acetate salt with high enantiomeric purity.",10.1021/op1003117,2011-02-04,0.6205994913127285
Organic Letters,Expedient Total Syntheses of WIN 64745 and WIN 64821,Bispyrrolidinoindoline diketopiperazine alkaloids were synthesized from a common intermediate in seven steps from commercially available amino acids. This versatile synthetic strategy has led to the accomplishment of the first total synthesis of heterodimeric WIN 64745 and a novel approach to homodimeric WIN 64821.,10.1021/ol8013073,2008-08-05,0.6205963788473782
Tetrahedron,A concise synthesis of (±)-methylenolactocin and the formal synthesis of (±)-phaseolinic acid,,10.1016/s0040-4039(01)00492-0,2001-05-01,0.6205921973671334
Journal of the American Chemical Society,"Total Synthesis of the Potent Androgen Receptor Antagonist (−)-Arabilin: A Strategic, Biomimetic [1,7]-Hydrogen Shift","The first total synthesis of (-)-arabilin, a Streptomyces metabolite that inhibits hormone activation of the androgen receptor, has been completed. The key step, a [1,7]-hydrogen shift, establishes the enol ether-containing skipped-tetraene substructure. This nonenzymatic pericyclic reaction is considered to be biomimetic.",10.1021/ja209459f,2011-11-16,0.620585126217025
Tetrahedron,The use of sodium chlorite in the non-racemic synthesis of a potent inhibitor of glycolipid biosynthesis,,10.1016/j.tetlet.2015.08.054,2015-08-21,0.6205750312208909
Organic Letters,Total Synthesis of the Glycosylated Macrolide Antibiotic Fidaxomicin,"The first enantioselective total synthesis of fidaxomicin, also known as tiacumicin B or lipiarmycin A3, is reported. This novel glycosylated macrolide antibiotic is used in the clinic for the treatment of Clostridium difficile infections. Key features of the synthesis involve a rapid and high-yielding access to the noviose, rhamnose, and orsellinic acid precursors; the first example of a β-selective noviosylation; an effective Suzuki coupling of highly functionalized substrates; and a ring-closing metathesis reaction of a noviosylated dienoate precursor. Careful selection of protecting groups allowed for a complete deprotection yielding totally synthetic fidaxomicin.",10.1021/acs.orglett.5b01602,2015-06-30,0.620551151318522
Journal of Organic Chemistry,Multi-Gram Scale Synthesis of FR180204,A concise synthesis of the ERK inhibitor FR180204 has been developed. The synthesis consists of six operationally simple steps and can be utilized to make multi-gram quantities of FR180204.,10.1021/jo901835m,2009-10-26,0.6205490089477811
Tetrahedron,"Structure of angelmicin B, A novel src signal transduction inhibitor",,10.1016/0040-4039(96)00428-5,1996-04-01,0.6205401680518631
Tetrahedron,The structure of a novel inhibitor of dextransucrase,,10.1016/s0040-4039(01)90292-8,1981-01-01,0.6205401680518631
Tetrahedron,Structure of grandinol: a novel root inhibitor from Eucalyptus grandis,,10.1016/s0040-4039(01)92832-1,1977-01-01,0.6205401680518631
Tetrahedron,"The structure of gloeosporone, a novel germination self-inhibitor from conidia of Collectotrichum gloeosporioides",,10.1016/s0040-4039(00)94040-1,1983-01-01,0.6205401680518631
Tetrahedron,An efficient one-step method for the synthesis of 2-(indolizin-2-yl)benzimidazoles from quinoxalinones and α-picoline via a novel rearrangement,,10.1016/j.tetlet.2008.08.032,2008-08-15,0.6205261798256895
Organic Process Research & Development,An Improved Synthesis of the Free Base and Diglycolate Salt of CEP-33779; A Janus Kinase 2 Inhibitor,"CEP-33779 is a triazole that has been reported to show highly selective inhibition of Janus kinase 2 (JAK2). An efficient process to form CEP-33779 will be presented that uses multiple palladium couplings to provide the drug substance in a convergent manner. The existing medicinal chemistry route was modified to avoid chromatographic purification, improve safety, and utilize palladium ligands which are available in quantities amenable to scale-up. Challenges faced during the development of the new process included optimization of conditions for Buchwald–Hartwig and Suzuki couplings, control of homocoupled impurities and removal of residual palladium. In addition, a screen of conditions to form a diglycolate salt of the parent compound are also presented.",10.1021/acs.oprd.6b00311,2016-11-30,0.620525256109628
Journal of Organic Chemistry,"Enantiospecific Synthesis of (<i>R</i>)-4-Amino-5-oxo-1,3,4,5-tetrahydrobenz[<i>cd</i>]indole, an Advanced Intermediate Containing the Tricyclic Core of the Ergots","We report a new strategy for the enantiospecific synthesis of (R)-4-amino-5-oxo-1,3,4,5-tetrahydrobenz[cd]indole. This compound is an advanced intermediate which contains the tricyclic core of many of the tetracyclic ergot alkaloids. Our method involves the initial synthesis of D-4-bromotryptophan from the coupling of an indolyllithium species with a masked serinal. The alpha-amino position was protected with an N-trityl group, ensuring the enantiomeric integrity of this position during the ensuing organometallic cyclization reaction. Stabilization of the tricycle was accomplished by protecting the indole nitrogen with a BOC group or by reducing the alpha-amino ketone to the corresponding beta-amino alcohol.",10.1021/jo981723s,1998-12-10,0.6205155512573135
European Journal of Organic Chemistry,"Stereoselective Syntheses of (+)‐Broussonetine D and (+)‐Australine via a Functionalized Pyrrolidine from an Extended Chiral 1,3‐Oxazine","The asymmetric syntheses of (+)‐broussonetine D and (+)‐australine have been achieved via a functionalized pyrrolidine obtained from an extended chiral 1,3‐oxazine. The key steps include pyrrolidine formation by oxazine cleavage and diastereoselective allylation to a pyrrolidine aldehyde. (+)‐Broussonetine D and (+)‐australine were synthesized from anti , syn , syn ‐oxazine, in six steps, with an overall yield of 22.2 %, and in seven steps, with an overall yield of 33.2 %.",10.1002/ejoc.201801552,2018-12-10,0.6205002051692758
European Journal of Organic Chemistry,A General Route to the Monomeric Subunits of the Macrotetrolides – A Short Synthesis of Methyl Nonactate,"A highly stereoselective and flexible sultone route to actic acids, the monomeric subunits of the macrotetrolides, has been developed and exemplified for nonactic acid (2a). Due to the extensive application of tandem transformations, only six steps were needed to secure methyl nonactate (20) from furan.",10.1002/(sici)1099-0690(199810)1998:10<2073::aid-ejoc2073>3.0.co;2-d,1998-10-01,0.6204901003706863
Synlett,Synthesis of the Key Skeleton of Phosphoeleganin,"Abstract The asymmetric synthesis of the key skeleton of phosphoeleganin has been achieved for the first time by using a convergent approach. The salient features of this synthesis include amidation to install a glycine amide at the C-1 position, Wittig olefination to access the C5–C6 bond, Julia–Kocienski olefinations to prepare the C9–C10 and C13–C14 bonds, and a Takai olefination and a Sonogashira coupling to construct the C17–C18 and C18–C19 bonds, respectively. The route disclosed is highly modular, which will permit the synthesis of various analogues, useful for structure–activity relationship studies on phosphoeleganins.",10.1055/a-1881-0529,2022-06-21,0.6204866441567897
European Journal of Organic Chemistry,Modular Total Syntheses of Lamellarin G Trimethyl Ether and Lamellarin S,"Abstract Modular total syntheses of the title compounds 2 and 3 are reported. The key pyrrolic building block 8 was prepared from the readily accessible pyrrole 6 via a di‐iodination/mono‐deiodination sequence. Suzuki–Miyaura cross‐coupling of compound 8 with boronate ester 9 afforded lactone 10 . Bromination of compound 10 followed by N ‐alkylation under Mitsunobu conditions afforded the fully substituted pyrrole 13 that engaged in a second Suzuki–Miyaura cross‐coupling reaction with boronic acid 14 to give compound 15 . Hydrolysis of the ester moiety within the last compound afforded acid 16 that engaged in a decarboxylative Heck cyclization process to give lamellarin G trimethyl ether ( 3 ). A related sequence of reactions starting from building block 8 and using the isopropoxy‐substituted arenes 22 , 25 and 27 has allowed for the completion of the first total synthesis of lamellarin S ( 2 ).",10.1002/ejoc.201001133,2010-11-09,0.6204845322536873
Journal of Organic Chemistry,Diastereoselective Total Synthesis of Isocarbacyclin from <scp>l</scp>-Ascorbic Acid,"Diastereoselective total synthesis of isocarbacyclin, which features a fused bicyclic key intermediate available from l-ascorbic acid, is described. The key intermediate was prepared in multigram quantities by the Pauson-Khand reaction of l-ascorbic acid-based (R)-4,4-diallyl-2,2-dimethyl-5-(trimethylsilyl)ethynyl-1,3-dioxolane (3), discriminating diastereotopic groups and faces of the geminal allyl substituents.",10.1021/jo048738c,2004-10-13,0.6204830677751069
Tetrahedron,A new route to N-Substituted 11-azaartemisinins,,10.1016/s0040-4039(96)02417-3,1997-02-01,0.620474173605733
Organic Process Research & Development,Development of New Catalytic Asymmetric Routes toward a Cost-Driving Building Block of Nirmatrelvir,"Nirmatrelvir is an inhibitor of the SARS-CoV-2 main protease and is the active ingredient in Paxlovid. Nirmatrelvir presents a significant synthetic challenge, in no small part due to a cost-driving lactam-containing fragment with two stereogenic centers. Our goal was to help decrease the cost of nirmatrelvir by developing a scalable low-cost synthesis of this fragment, avoiding the use of cryogenic conditions reported in the initial route. Herein, we disclose three catalytic asymmetric routes toward this fragment, via (i) chiral Lewis acid (copper) catalysis, (ii) chiral Bro̷nsted base organocatalysis, and (iii) chiral bifunctional hydrogen-bond-donor organocatalysis.",10.1021/acs.oprd.4c00109,2024-05-28,0.6204714780315399
Synlett,An Expedient Synthesis of Regioisomeric Pyrazole-Fused Cycloalkanones,"Described herein is a novel one-pot procedure for the synthesis of pyrazoles through the in situ generation of a monohydrazone of cyclic 1,3-diones and subsequent cyclization with N,N-dimethylformamide dimethyl acetal. This route provides pyrazoles that have limited accessibility by other methods.",10.1055/s-2008-1032086,2008-02-12,0.6204664183280963
Synthesis,Synthesis of the Northern Hemisphere of Amphidinolide H2,"The stereoselective synthesis of the fully functionalized northern hemisphere of the marine natural product amphidinolide H2 is described. A vinylogous Mukaiyama aldol reaction and enzymatic desymmetrization of a meso compound are the key steps in the fragment synthesis. A stereoselective acetate aldol coupling and a 1,3-anti-reduction of the resulting β-hydroxy ketone complete the synthesis of the C14-C26 fragment.",10.1055/s-2006-942459,2006-07-25,0.6204626133986689
Tetrahedron,"A highly enantioselective synthesis of (R)-(-)-2-acetyl-5,8-dimethoxy-1,2,3,4-tetrahydro-2-naphthol. A key intermediate in the synthesis of anthracyclinones",,10.1016/s0040-4039(00)92107-5,1991-02-01,0.6204614999440983
Synlett,Process Development of Halaven®: Synthesis of the C14-C35 Fragment via Iterative Nozaki-Hiyama-Kishi Reaction-Williamson Ether Cyclization,Multikilogram manufacturing process of the Halaven ® C14–C35 fragment is described. The synthesis features convergent assembly of subunits by iterative asymmetric Ni/Cr-mediated coupling executed in fixed equipment.,10.1055/s-0032-1317920,2013-01-10,0.6204529417610393
Organic Letters,Synthesis of the C10−C32 Core Structure of Spirangien A,The synthesis of the C10-C32 core structure of spirangien A is reported. The pivotal aldol coupling between both key intermediates provides a synthetic challenge in the synthesis of this complex natural product.,10.1021/ol8018105,2008-08-28,0.6204493910798687
Synthesis,An Improved Synthesis of 4-Methoxy-2-naphthylamine,,10.1055/s-1974-23384,1974-01-01,0.6204445438414962
Journal of the American Chemical Society,Total Synthesis of (+)-Suaveolindole:  Establishment of Its Absolute Configuration,"This communication describes two approaches toward the total synthesis of (+)-suaveolindole. The initial strategy uses a 6- exo -Heck cyclization to generate a transient sp 3 carbopalladate. This intermediate was successfully coupled with an indole 3-stannane to assemble the majority of the carbon framework of the natural product. However, due to problems described herein, this interesting route was not viable. To reach our target, lessons learned from the first strategy directed us to develop a significant extension of the Ireland ester enolate rearrangement in which the tetra-substituted isopropylidene group and the α-disposed carboxymethyl function are introduced in a single event. This key reaction enables a remarkably concise inaugural synthesis of (+)-suaveolindole.",10.1021/ja075100k,2007-08-14,0.6204440618068898
Organic Letters,Total Synthesis of (−)-Anisatin,"A novel synthetic route to (-)-anisatin has been developed. Our synthesis features a rhodium-catalyzed 1,4-addition of an arylboronic acid, an intramolecular Diels-Alder reaction of an ortho-quinone monoketal, a stereoselective [2,3]-Wittig rearrangement, and construction of the oxabicyclo [3.3.1] skeleton via cleavage of an epoxide by a primary amide.",10.1021/ol300390k,2012-02-28,0.6204435334166667
Journal of the American Chemical Society,Thionium Ion Initiated Medium-Sized Ring Formation: The Total Synthesis of Asteriscunolide D,"The first synthesis of the biologically active humulene natural product asteriscunolide D has been accomplished in nine steps without the use of protecting groups. The challenging 11-membered ring was forged via a diastereoselective thionium ion initiated cyclization, which constitutes a formal aldol disconnection to form a strained macrocycle. A stereospecific thioether activation-elimination protocol was developed for selective E-olefin formation, thus providing access to the most biologically active asteriscunolide. The absolute stereochemical configuration was established by the Zn-ProPhenol catalyzed enantioselective addition of methyl propiolate to an aliphatic aldehyde to afford a γ-hydroxy propiolate as a handle for butenolide formation via Ru-catalyzed alkene-alkyne coupling.",10.1021/ja210986f,2012-01-05,0.6204432864447651
Journal of Organic Chemistry,Synthesis of (+)-Lineariifolianone and Related Cyclopropenone-Containing Sesquiterpenoids,"A synthesis of the proposed structure of lineariifolianone has been achieved in eight steps and 9% overall yield starting from (+)-valencene, leading to a reassignment of the absolute configuration of this unusual cyclopropenone-containing natural product. Key steps in the synthetic route include kinetic protonation of an enolate to epimerize the C7 stereocenter and a stereoconvergent epoxide opening to establish the trans-diaxial diol functionality. The syntheses of the enantiomers of two other closely related natural products are also reported, confirming that all three compounds belong to the eremophilane class of sesquiterpenoids.",10.1021/acs.joc.9b00478,2019-04-02,0.6204241344347302
Journal of the American Chemical Society,Asymmetric Total Synthesis of Pre-schisanartanin C,"Pre-schisanartanin C belongs to the family of Schisandra nortriterpenoids with potent antihepatitis, antitumor, and anti-HIV activities. This paper presents the enantioselective total synthesis of pre-schisanartanin C ( 1 ). An important step in the total synthesis of 1 is gold-catalyzed intramolecular cyclopropanation of a 1,8-enyne substrate bearing a secondary ester group at the propargylic position to prepare a bicyclo[6.1.0]nonane core. Additional highlights include (i) an asymmetric Diels–Alder reaction to install the initial C5 stereogenic center of 1 and (ii) a sequential Pd-catalyzed Stille coupling, regio- and stereoselective Sharpless asymmetric dihydroxylation, and a subsequent intramolecular lactonization to construct the side chain of 1 . The developed chemistry paves the way for the total syntheses of other family members bearing highly rigid bicyclo[6.1.0]nonane cores.",10.1021/jacs.9b11872,2019-12-02,0.6204085426547188
Journal of the American Chemical Society,Asymmetric total synthesis of erythromycin. 3. Total synthesis of erythromycin,"In the preceding paper' we described the preparation of the&#13;\nkey lactone intermediate la in optically active form. In this paper we report the synthesis of erythromycin (2) from la. In essence,this transformation involves the glycosidation of a suitable derivative of la with L-cladinose and D-desosamine and the generation of the C-9 ketone functionality.",10.1021/ja00401a051,1981-06-01,0.6203939558886217
Tetrahedron,Enantioselective synthesis of the nagilactone ring system via vinylsilane-mediated polyene cyclization,,10.1016/s0040-4039(01)93878-x,1989-01-01,0.6203911338654367
Tetrahedron,"Sol-gel entrapped chromium(VI): a new selective, efficient and recyclable oxidizing system",,10.1016/s0040-4039(01)00975-3,2001-07-01,0.6203868480442325
Tetrahedron,"Total synthesis and absolute stereochemistry of (9R,10S)-epoxyheptadecan-4,6-diyn-3-one, a diacylglycerol acyltransferase inhibitor from Panax ginseng",,10.1016/j.tetlet.2004.07.153,2004-08-27,0.6203859182846578
Tetrahedron,A practical one-pot synthesis of O-unprotected glycosyl thioureas,,10.1016/s0040-4039(01)01039-5,2001-08-01,0.6203775290926363
Organic Letters,Enantioselective Total Synthesis of Fluvirucinin B<sub>1</sub>,"A convergent synthesis of fluvirucinin B1 from acid ent-6a and nitrile ent-9, involving an organocopper coupling, a stereoselective allylation, a ring-closing metathesis reaction, and a stereoselective hydrogenation as the key steps, is reported. The starting building blocks have been prepared in a straightforward manner from a common phenylglycinol-derived lactam 1. An unprecedented regioselective oxidation of phenylglycinol-derived secondary amines 5 to carboxylic acids 6 has been developed.",10.1021/acs.orglett.6b00513,2016-04-05,0.6203745887760455
Organic Process Research & Development,Optimized Synthesis of the Key Intermediate of Telmisartan via the Cyclization of 2-Bromoarylamine with <i>n</i>-Butyronitrile,"Herein, a facile and sustainable synthesis method of bis-benzimidazole compound 5, which is the key intermediate of telmisartan, is realized using commercially available 3-methyl-4-nitrobenzoic acid and 2-chloronitrobenzene as starting materials. Aniline 10 was produced in 98% isolated yield using a one-pot reduction/cyclization procedure. Subsequently, 2-bromoarylamine 11 was prepared in 96% isolated yield via the bromination of aniline 10 with bromine. Finally, bis-benzimidazole 5 synthesis was completed via the cyclization of 2-bromoarylamine 11 with n -butyronitrile; the isolated yield of bis-benzimidazole 5 was 95%, and its high-performance liquid chromatography purity based on area was 99.8%. Each reaction step was optimized to achieve high yields, and the optimal conditions were identified in the final step via the design of experiments. The developed process provides an alternative sustainable route for synthesizing bis-benzimidazole 5; this route avoids undesired nitration using nitric/sulfuric acid and cyclization in polyphosphoric acid, which are used in the current methods.",10.1021/acs.oprd.3c00298,2023-11-06,0.6203421878355138
Organic Process Research & Development,"Toward a Scalable Synthesis and Process for EMA401, Part I: Late Stage Process Development, Route Scouting, and ICH M7 Assessment","We present the enantioselective synthesis of sodium (3 S )-5-(benzyloxy)-2-(diphenylacetyl)-6-methoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylate (EMA401, olodanrigan), an angiotensin II type 2 antagonist. The manuscript features the process optimizations of the end game used for late phase clinical supplies, an overview of synthetic strategies identified in a route scouting exercise to a key intermediate phenylalanine derivative, and the analytical control strategy of the potentially formed highly toxic impurity bis(chloromethyl) ether (BCME). Starting from the phenylalanine derivative, we describe the optimizations of the end game from early phase to late phase processes with consequent improvements in the PMI factor. This sequence includes a Pictet–Spengler cyclization and an amide coupling as the last bond-forming steps, and the manufacturing process was successfully implemented on a 175 kg scale in a pilot plant setup. The modified process conditions eliminated one step by in situ activation of the carboxylic acid, avoided the REACH listed solvent DMF, and resulted in a PMI improvement by a factor of 3. In the final crystallization, a new, thermodynamically more stable modification of the drug substance was found in the complex solid-state landscape of EMA401 during an extensive polymorph screening. A process suitable for large-scale production was developed to prepare the new polymorph, avoiding the need of any special equipment such as fluidized bed drying required in the early phase process. In the second section, some of the synthetic approaches investigated for the route scouting of the phenylalanine derivative key intermediate are presented. To conclude, we discuss the analytical control strategy for BCME, the formation of which, due to the simultaneous presence of HCl and CH 2 O in the Pictet–Spengler cyclization, could not be ruled out. The BCME purge factor calculations using the tools of ICH M7 control option 4 are compared to actual results from spiking experiments.",10.1021/acs.oprd.0c00215,2020-08-20,0.6203377782492006
Journal of Organic Chemistry,Total Synthesis of Archaeal 36-Membered Macrocyclic Diether Lipid,"Total synthesis of archaeal 36-membered macrocyclic diether lipid 2 is reported. The synthesis is based upon stereoselective preparation of functionalized isoprenoid chains, ether-linkage formation between the isoprenoid chains with a glycerol derivative, and the ultimate intramolecular dicarbonyl coupling using low-valent titanium known as McMurry coupling. This synthetic method has successfully provided the first practical route to chemically defined archaeal macrocyclic membrane lipids, which were not available because of the lack of synthetic access. Also described is a highly stereoselective and convenient synthesis of stereochemically homogeneous archaeal biphytanyl glycerol lipid 1.",10.1021/jo962327h,1997-04-01,0.6203346180909831
Angewandte Chemie International Edition,Total Synthesis and Biological Evaluation of the Glycosylated Macrocyclic Antibiotic Mangrolide A,"The macrocyclic antibiotic mangrolide A has been described to exhibit potent activity against a number of clinically important Gram-negative pathogens. Reported is the first enantioselective total synthesis of mangrolide A and derivatives. Salient features of this synthesis include a highly convergent macrocycle preparation, stereoselective synthesis of the disaccharide moiety, and two β-selective glycosylations. The synthesis of mangrolide A and its analogues enabled the re-examination of its activity against bacterial pathogens, and only minimal activity was observed.",10.1002/anie.201805770,2018-06-26,0.6203299841020106
European Journal of Organic Chemistry,"Total Synthesis of Luminmycin A, a Cryptic Natural Product from <i>Photorhabdus Luminescens</i>","Luminmycin A, a natural proteasome inhibitor transcripted by a silent gene cluster from Photorhabdus luminescens , belongs to the compound family of the syrbactins and is structurally closely related to the glidobactins. Key step for the synthesis of the 12‐membered cyclopeptide ring is an intramolecular Horner–Wadsworth–Emmons reaction, while the double unsaturated fatty acid side chain can be obtained via phosphane‐catalyzed isomerization of a corresponding acetylenic fatty acid ester.",10.1002/ejoc.201900460,2019-04-18,0.6202985440841177
Journal of Organic Chemistry,"Efficient, Stereoselective Synthesis of 24(<i>S</i>),25-Epoxycholesterol","Efficient, stereoselective syntheses of 24( S ),25-epoxycholesterol ( 1 ) have been developed starting from cholenic acid ( 4 ) or stigmasterol ( 8 ), both featuring as the key step Sharpless asymmetric dihydroxylation of desmosterol acetate ( 2 ). This work permits preparation of gram quantities of 1 for further evaluation as a natural regulator of cholesterol metabolism, specifically, e.g., as a ligand for the LXRα nuclear receptor.",10.1021/jo981753v,1998-12-01,0.6202750218058088
Journal of Organic Chemistry,Enantioselective Synthesis of (−)-Pumiliotoxin C from a Chiral Amino Ester and an Acetylenic Sulfone that Acts as an Alkene Dipole Equivalent,"A new synthesis of the naturally occurring (−)-enantiomer of the dendrobatid alkaloid pumiliotoxin C ( 1 ) was achieved by the conjugate addition of methyl (−)- cis -2-amino- trans -6-methylcyclohexanecarboxylate ( 3 ) to 1-( p -toluenesulfonyl)-1-pentyne ( 4 ), followed by intramolecular acylation to afford (4a S,5 R,8a R )-4a,5,6,7,8,8a-hexahydro-5-methyl-2-propyl-3-( p -toluenesulfonyl)-4-quinolinone ( 2 ). The acetylenic sulfone thus acts as the synthetic equivalent of an alkene dipole species. The required enantiopure amino ester 3 was obtained by an approach based on pig liver esterase (PLE)-mediated hydrolysis. Thus, the (−)- and (+)-enantiomers of racemic dimethyl trans -3-methylcyclohexane- cis, cis -1,2-dicarboxylate ( 6 ) afforded the corresponding half-esters 7 and 8, respectively, when treated with PLE. The desired half-ester 7 was recovered intact after selective conversion of the free carboxylic acid group of the byproduct 8 into its benzyl ester. Half-ester 7 was converted into enantiopure (−)- 6 with diazomethane, followed by regioselective saponification and Curtius rearrangement to afford the required enantiopure key intermediate 3 . Finally, hydrogenation of the enol triflate of enaminone 2, followed by reductive desulfonylation, afforded the product (−)- 1 .",10.1021/jo980647q,1998-08-25,0.6202723313318367
Organic Letters,"A Cycloisomerization/Friedel–Crafts Alkylation Strategy for the Synthesis of Pyrano[3,4-<i>b</i>]indoles","The synthesis of pyrano[3,4-b]indoles is described. The reaction sequence involves Sonogashira coupling of dihydropyran propargyl ether scaffolds with iodoanilines to afford intermediate indoles. Lewis acid-catalyzed ionization of the dihydropyrans, followed by intramolecular C3 alkylation of the indole, provides the title compounds.",10.1021/ol201532k,2011-07-08,0.6202675459453791
Organic Letters,Protecting-Group-Free Synthesis of Cassane-Type Furan Diterpenes via a Decarboxylative Dienone–Phenol Rearrangement,"An expeditious route to obtaining cassane-type furan diterpenes starting from (+)-sclareolide, an inexpensive commercially available natural lactone, has been achieved by using a solvent-free Diels-Alder cycloaddition and an unprecedented decarboxylative dienone-phenol rearrangement as key steps. Its applicability is showcased by the first synthesis of (5α)-vouacapane-8(14),9(11)-diene. The synthesis, which requires no protecting group, is efficient and atom- and step-economical (10 steps, 20% global).",10.1021/acs.orglett.8b02867,2018-10-29,0.6202633861366078
Angewandte Chemie International Edition,Enantioselective Total Synthesis of (−)‐Terengganensine A,"A seven-step enantioselective total synthesis of (-)-terengganensine A, a complex heptacyclic monoterpene indole alkaloid, was accomplished. Key steps included: a) Noyori's catalytic enantioselective transfer hydrogenation of the iminium salt to set up the absolute configuration at the C21 position; b) a highly diastereoselective C7 benzoyloxylation with dibenzoyl peroxide under mild conditions; and c) an integrated one-pot oxidative cleavage of cyclopentene/triple cyclization/hydrolysis sequence for the construction of the dioxa azaadamantane motif with complete control of four newly generated stereocenters.",10.1002/anie.201602374,2016-04-20,0.6202414146915817
Synlett,"Development of In-Water Scalable Process for the Preparation of [2-(3-Bromo-2-methylphenyl)-7-chloro-1,3-benzoxazol-5-yl]methanol, a Key Intermediate in the Synthesis of Potent PD-1/PD-L1 Inhibitors","Abstract We propose a synthetic process for the preparation of a benzoxazole building block for a programmed death-ligand 1 inhibitor that is a candidate currently under clinical investigation for cancer treatment. Our research focused on searching for mild, scalable, and ecofriendly conditions for the synthesis of benzoxazoles. To reduce the use of toxic reagents or solvents and to minimize the production of organic wastes, the cyclization reaction was performed in an aqueous micellar medium. This in-water benzoxazole synthesis gave comparable yields to previously reported processes, and was applied to a broad range of benzoxazoles with various substitution patterns, showcasing its effectiveness in ecofriendly benzoxazole cyclization reactions.",10.1055/s-0043-1774944,2024-07-01,0.6202398906336731
Tetrahedron,Regioselective single electron transfer photocatalytic synthesis of 2-cyano-3-ethylidenepiperidines. New route to the total synthesis of (±) cis-eburnamonine,,10.1016/0040-4039(95)00233-3,1995-03-01,0.6202354160370039
Journal of the American Chemical Society,Total Synthesis of the Akuammiline Alkaloid Picrinine,"We report the first total synthesis of the complex akuammiline alkaloid picrinine, which was first isolated nearly five decades ago. Our synthetic approach features a concise assembly of the [3.3.1]-azabicyclic core, a key Fischer indolization reaction to forge the natural product's carbon framework, and a series of delicate late-stage transformations to complete the synthesis. Our synthesis of picrinine also constitutes a formal synthesis of the related polycyclic alkaloid strictamine.",10.1021/ja501780w,2014-03-05,0.6202323073844398
Angewandte Chemie International Edition,Total Synthesis of (−)‐Norzoanthamine,"No bones about it: (-)-Norzoanthamine, a promising candidate for an anti-osteoporotic drug, was the target of a total synthesis (see scheme). The final bisaminal formation with AcOH/H(2)O gave the DEFG ring, while the cyclization precursor was prepared by installing the remaining bisaminal unit after oxidative cleavage of the cyclopentanol moiety.",10.1002/anie.200804546,2008-12-03,0.6202280503362261
Tetrahedron,Pyridine radicals in synthesis: A formal total synthesis of (±)-oxerine,,10.1016/0040-4039(96)01822-9,1996-10-01,0.6202212783652133
Organic Letters,Total Synthesis of (−)-Blepharocalyxin D and Analogues,"An efficient strategy for the total synthesis of (-)-blepharocalyxin D and an analogue is described. The key step involves an acid-mediated cascade process in which reaction of methyl 3,3-dimethoxypropanoate with γ,δ-unsaturated alcohols possessing diastereotopic styrenyl groups gives trans-fused bicyclic lactones with the creation of two rings and four stereocenters in one pot.",10.1021/ol400736w,2013-04-05,0.6202111017397822
Tetrahedron,"Asymmetric synthesis xx preparation of a novel spiropiperidine system by the CN(R,S) method",,10.1016/s0040-4039(01)93883-3,1989-01-01,0.6202050012905704
Organic Letters,"A New DNA Building Block, 4′-Selenothymidine: Synthesis and Modification to 4′-Seleno-AZT as a Potential Anti-HIV Agent","The first synthesis of 4'-selenothymidine (1), a novel DNA building block, and 4'-seleno-AZT (2) was accomplished from 2-deoxy-d-ribose via stereoselective formation of 2-deoxy-4-seleno-d-furanose 17 and a Pummerer-type base condensation as key steps. 4'-Selenothymidine (1) was discovered to adopt the same 2'-endo/3'-exo conformation as thymidine, which is unusual in that 4'-selenouridine has the opposite conformation to that of uridine.",10.1021/ol1005906,2010-04-20,0.6202001944165381
Synthesis,"An Efficient Synthesis of New 7-Trifluoromethyl-2,5-disubstituted Pyrazolo[1,5-a]pyrimidines","A novel two-step synthesis of trifluoromethylated 3,5-disubstituted pyrazolo[1,5-a]pyrimidines is reported from 3-aminopyrazoles and ethyl 4,4,4-trifluorobut-2-ynoate. The synthetic route begins with the one-pot synthesis of 7-trifluoromethylated pyrazolo[1,5-a]pyrimidin-5-ones by condensation of 3-aminopyrazoles with a fluorinated alkyne. The products obtained are used as building blocks to synthesize directly, with excellent yields via C–O bond activation, a library of new fluorinated 3,5-disubstituted pyrazolo[1,5-a]pyrimidines of biological interest. This operation efficiently allows C–C, C–N and C–S bond formation.",10.1055/s-0036-1591752,2018-01-22,0.6201940367082344
Tetrahedron,A simplified route to the phosphatidylinositol cascade inhibitor --- (-)-1L-1-deoxy-1-fluoro-Myo-inositol,,10.1016/s0040-4039(00)99246-3,1989-01-01,0.6201890515691596
Journal of Organic Chemistry,Biocatalytic Stereoselective Synthesis of Chiral Precursors for Liposoluble β<sub>1</sub> Receptor Blocker Nebivolol,"Asymmetric reduction of 2-chloro-1-(6-fluorochroman-2-yl)ethan-1-one (NEB-7) into 2-chloro-1-(6-fluorochroman-2-yl)ethan-1-ol (NEB-8) is the crucial step for synthesis of liposoluble β 1 receptor blocker nebivolol. Four efficient and stereoselective alcohol dehydrogenases were identified, enabling the stereoselective synthesis of all enantiomers of NEB-8 at a substrate loading of 137 g·L –1 with ee values of >99% and high space-time yields. This study provides novel biocatalysts for the efficient synthesis of nebivolol precursors and uncovers the molecular basis for enantioselectivity manipulation by parametrization of Prelog’s rule.",10.1021/acs.joc.4c01027,2024-07-23,0.6201758278099113
Organic Process Research & Development,Early Development Scale-Up of a Structurally-Challenging 5-Lipoxygenase Activating Protein (FLAP) Inhibitor,"A practical and efficient synthesis of the FLAP inhibitor 1 was developed addressing multiple scale-up and safety concerns posed by the established synthesis and utilized a resolution strategy (replacing supercritical fluid chromatography (SFC) separation) for expedient access to the key structural component of 1: the challenging chiral quaternary center. Also highlighted are in situ IR monitoring, condensation to form the 1,2,4-oxadiazole ring, and an efficient Suzuki-Miyaura coupling.",10.1021/acs.oprd.7b00202,2017-06-30,0.6201721774544201
Tetrahedron,Synthesis of conformationally restricted analogues of the tryptophanyl tRNA synthetase inhibitor indolmycin,,10.1016/0040-4039(96)00471-6,1996-04-01,0.6201675034349777
Tetrahedron,Highly efficient and enantioselective synthesis of l-arylglycines and d-arylglycine amides from biotransformations of nitriles,,10.1016/s0040-4039(01)01439-3,2001-09-01,0.6201652830200081
Organic Letters,Total Synthesis of (±)-Hirsutine: Application of Phosphine-Catalyzed Imine–Allene [4 + 2] Annulation,"The total synthesis of the indole alkaloid hirsutine has been achieved, with a key step being the application of our phosphine-catalyzed [4 + 2] annulation of an imine with ethyl α-methylallenoate. From commercially available indole-2-carboxaldehyde, the target was synthesized in 14 steps and 6.7% overall yield.",10.1021/ol302077n,2012-08-24,0.620165074021395
Journal of Organic Chemistry,Synthesis of (.+-.)-.alpha.- and (.+-.)-.gamma.-lycorane via a stereocontrolled organopalladium route,"Total syntheses of (+/-)-alpha-and (+/-)-gamma-lycorane are described. The key steps in the syntheses are the stereocontrolled palladium-catalyzed intramolecular 1,4-chloroamidation of 12 to 13 and the subsequent anti-stereoselective copper-catalyzed S(N)2' reaction of allylic chloride 13 with [3,4-(methylenedioxy)phenyl]magnesium bromide to give 14. Hexahydroindole 14 has the required relative stereochemistry between carbons 3a, 7, and 7a for alpha-lycorane (1a) and was transformed to the latter via 15 and 16. The epimeric gamma-lycorane (2) was obtained by performing the Bischler-Napieralski cyclization on 14, which led to a highly stereoselective isomerization to give exclusively 17. Compound 17 was subsequently transformed to 2. The overall yield from ester 8 to (+/-)-alpha- and (+/-)-gamma-lycorane was 40 and 36%, respectively.",10.1021/jo00009a011,1991-04-01,0.6201647208983834
Tetrahedron,"Stereoselective synthesis of a new perhydroindole derivative of chiral iminodiacid, a potent inhibitor of angiotensin converting enzyme",,10.1016/s0040-4039(00)87188-9,1982-01-01,0.6201495214630158
Journal of Organic Chemistry,"Synthesis of the 1,5-Diazabicyclo[6.3.0]dodecane Core Structure of Xevinapant","Inhibitors of apoptosis proteins (IAPs) are key targets in cancer therapy due to their role in promoting cancer cell survival. The second mitochondria-derived activator of caspases (SMAC) mimetics, which antagonize IAPs, have shown therapeutic potential for cancers. 1,5-Diazabicyclo[6.3.0]dodecanone amino acid scaffold serves as an important scaffold for developing SMAC mimetics, including clinical candidates like Xevinapant and Dasminapant. Herein, we report a novel, efficient, and potentially scalable synthesis of the core structure of Xevinapant achieved in 7 steps from a pyroglutamic acid derivative, with an overall yield of 8.4%, facilitating further development of IAP inhibitors.",10.1021/acs.joc.5c01930,2025-09-17,0.6201362999752101
Tetrahedron,An improved method for the synthesis of anhydroalditols,,10.1016/0040-4039(95)00618-m,1995-05-01,0.6201234219662414
Synthesis,An Improved Method for the Synthesis of Benzils from Benzoins,,10.1055/s-1974-23413,1974-01-01,0.6201234219662414
Synthesis,An Improved Method for the Synthesis of 2β-Hydroxytestosterone,,10.1055/s-1971-21746,1971-01-01,0.6201234219662414
Tetrahedron,An improved method for the synthesis of anomerically allylated C-glycopyranosides and C-glycofuranosides.,,10.1016/s0040-4039(00)81710-4,1983-01-01,0.6201234219662414
Tetrahedron,A new synthetic route for the preparation of β-acyloxy mercaptans via the addition of thioacids to epoxides,,10.1016/j.tetlet.2012.03.045,2012-03-21,0.6201215750982235
Tetrahedron,Toward new camptothecins. Part 7: Synthesis of thioluotonin and its 5-methoxycarbonyl derivative,,10.1016/j.tetlet.2011.01.105,2011-02-07,0.6201185469360908
Tetrahedron,New synthesis of pyridone derivative from 1-azadiene,,10.1016/s0040-4039(01)82016-5,1981-01-01,0.6201185469360908
Tetrahedron,Synthesis of norambracetal: A new ambergris derivative.,,10.1016/s0040-4039(00)93396-3,1993-05-01,0.6201185469360908
Tetrahedron,Synthesis of a new CTX derivative with naphthalene units,,10.1016/j.tetlet.2024.155449,2025-01-04,0.6201185469360908
Tetrahedron,"Synthesis of napavin, a new photoreactive derivative of vinblastine",,10.1016/s0040-4039(01)93495-1,1989-01-01,0.6201185469360908
Tetrahedron,Synthesis of 2′(3′)-0-aminoacyl triribonucleoside diphosphates with the sequence of the acceptor terminus of AA-tRNA,,10.1016/0040-4039(81)80007-x,1981-01-01,0.6201171302108784
Tetrahedron,"Chemistry of adamantane. VIII. Synthesis of 1,2-difunctional adamantanes using protoadamantane-4-spiroöxirane as a novel intermediate.",,10.1016/s0040-4039(00)75090-8,1975-01-01,0.6201121153998899
Journal of the American Chemical Society,Total Synthesis of the Reported Structure of Neaumycin B,"assigned to the macrolide natural product neaumycin B is reported in a 2.3% overall yield on 90 mg scale. The synthesis features a gram-scale nickel-catalyzed reductive cross-coupling/spiroketalization tactic to construct the spiroketal core of neaumycin B. The stereostructures of the C3-C6, C8-C14, and C20-C41 segments of synthetic neaumycin B were unambiguously verified by X-ray crystallography.",10.1021/jacs.3c06573,2023-08-10,0.6201035772098948
Organic Letters,Enantioselective Allyltitanation. Efficient Synthesis of the C1−C14 Polyol Subunit of Amphotericin B,"[structure] An efficient synthesis of the C(1)-C(14) fragment of amphotericin B is described. This synthesis is based on the formation of syn-1,3-diols from enantioselective allyltitanation of unprotected beta-hydroxyaldehydes.",10.1021/ol0063914,2000-11-15,0.6200775533845944
Journal of the American Chemical Society,C−C Bond Formation via C−H Bond Activation:  Synthesis of the Core of Teleocidin B4,"The core of teleocidin B4, a complex fragment of a natural product containing two quaternary stereocenters and a penta-substituted benzene ring, was synthesized in four C-C bond-forming steps starting from tert-butyl derivative 1. The first step involved alkenylation of the tert-butyl group with a vinyl boronic acid, followed by the successful annulation of the cyclohexane ring to the benzene nucleus via an intramolecular Friedel-Crafts reaction. The third step required a diastereoselective oxidative carbonylation of the geminal dimethyl group, followed at last by indole assembly via the alkenylation of the phenol nucleus, to afford the teleocidin B4 core. Noteworthy is the fact that steps 1 and 3 critically depended on the directing role of the aniline nitrogen (directed C-H bond functionalization).",10.1021/ja027311p,2002-09-14,0.6200752274130881
Tetrahedron,Asymmetric synthesis of (−)-(R)-sitagliptin,,10.1016/j.tetlet.2012.04.025,2012-04-12,0.6200607336197731
Tetrahedron,Asymmetric synthesis of erythro-β-hydroxyasparagine,,10.1016/j.tetlet.2008.12.103,2009-01-09,0.6200607336197731
Tetrahedron,Asymmetric synthesis of (+)-tetrahydropseudodistomin,,10.1016/j.tetlet.2007.01.143,2007-02-02,0.6200607336197731
Tetrahedron,Asymmetric synthesis of (+)- and (−)-deoxyfebrifugine and deoxyhalofuginone,,10.1016/j.tetlet.2015.09.146,2015-10-24,0.6200607336197731
Tetrahedron,An asymmetric synthesis of (+)-kjellmanianone,,10.1016/s0040-4039(01)82963-4,1981-01-01,0.6200607336197731
Tetrahedron,"An asymmetric synthesis of D-1,6-Diepicastanospermine",,10.1016/s0040-4039(00)60010-2,1992-10-01,0.6200607336197731
Tetrahedron,Asymmetric synthesis of S-(−)-cucurbitine,,10.1016/s0040-4039(00)61768-9,1992-11-01,0.6200607336197731
Tetrahedron,Asymmetric synthesis of dienomycin C,,10.1016/s0040-4039(98)02273-4,1999-01-01,0.6200607336197731
Tetrahedron,An asymmetric synthesis of (+)-phyllanthocin,,10.1016/s0040-4039(00)74285-7,1991-03-01,0.6200607336197731
Tetrahedron,Asymmetric synthesis. Part V. Acetylenic carbinols,,10.1016/s0040-4039(01)96854-6,1971-01-01,0.6200607336197731
Tetrahedron,An asymmetric synthesis of (+)-desoxoprosophylline,,10.1016/j.tetlet.2008.06.074,2008-06-20,0.6200607336197731
Tetrahedron,An asymmetric synthesis of sulfobacin A,,10.1016/j.tetlet.2007.03.115,2007-03-27,0.6200607336197731
Tetrahedron,Asymmetric synthesis XVIII,,10.1016/s0040-4039(01)93468-9,1989-01-01,0.6200607336197731
Tetrahedron,Asymmetric synthesis of (−)-acaterin,,10.1016/s0040-4039(03)01412-6,2003-07-16,0.6200607336197731
Tetrahedron,Towards an asymmetric synthesis of ADDA conjugates,,10.1016/s0040-4039(98)00946-0,1998-07-01,0.6200607336197731
Tetrahedron,Asymmetric synthesis of (−)- and (+)-neodichroine/hydrachine A from (+)- and (−)-febrifugine,,10.1016/j.tetlet.2018.03.035,2018-03-15,0.6200607336197731
Tetrahedron,Asymmetric synthesis of (+)-abresoline,,10.1016/j.tetlet.2005.02.110,2005-03-11,0.6200607336197731
Tetrahedron,Asymmetric synthesis of all the stereoisomers of tarchonanthuslactone,,10.1016/j.tetlet.2005.08.164,2005-09-16,0.6200607336197731
Tetrahedron,Asymmetric synthesis of (−)-codonopsinine,,10.1016/j.tetlet.2011.09.114,2011-09-30,0.6200607336197731
Tetrahedron,Synthesis of asymmetric systines,,10.1016/s0040-4039(98)01614-1,1998-10-01,0.6200607336197731
Tetrahedron,Asymmetric synthesis of 1-alkynylcyclopropane-1-carboxylates,,10.1016/s0040-4039(00)01453-2,2000-10-01,0.6200607336197731
Tetrahedron,Asymmetric synthesis of (E)-dehydroapratoxin A,,10.1016/j.tetlet.2011.05.107,2011-06-26,0.6200607336197731
Tetrahedron,"Synthesis and morphology of asymmetric, alkyne-functionalised pentacene and 2-fluoroanthradithiophene",,10.1016/j.tetlet.2013.10.006,2013-10-11,0.6200607336197731
Tetrahedron,Asymmetric synthesis of the marine alkaloid (−)-(S)-nakinadine C,,10.1016/j.tetlet.2013.09.043,2013-09-21,0.6200607336197731
Tetrahedron,Asymmetric synthesis of (+)-1-deoxynojirimycin,,10.1016/s0040-4039(98)01536-6,1998-09-01,0.6200607336197731
Tetrahedron,The asymmetric synthesis and stereochemical assignment of chelonin B,,10.1016/s0040-4039(01)01555-6,2001-10-01,0.6200607336197731
Tetrahedron,"Asymmetric synthesis of (−)-(S,S)-homaline",,10.1016/j.tetlet.2011.12.088,2011-12-30,0.6200607336197731
Tetrahedron,Synthesis of asymmetric (E)-α-(2-phenylcyclopropyl)glycines,,10.1016/s0040-4039(00)79491-3,1991-01-01,0.6200607336197731
Tetrahedron,Asymmetric synthesis of the four stereoisomers of 5-deoxystrigol,,10.1016/j.tetlet.2014.10.040,2014-10-13,0.6200607336197731
Tetrahedron,"Asymmetric synthesis of 1,2- and 1,4-dihydroquinolines",,10.1016/s0040-4039(99)01172-7,1999-08-01,0.6200607336197731
Tetrahedron,Asymmetric synthesis of alkannin and shikonin,,10.1016/s0040-4039(97)01687-0,1997-10-01,0.6200607336197731
Tetrahedron,Asymmetric synthesis of (R)- and (S)-2-trifluoromethylepinephrine,,10.1016/j.tetlet.2004.02.040,2004-03-01,0.6200607336197731
Tetrahedron,Asymmetric synthesis of (+)-passifloricin A and its 6-epimer,,10.1016/j.tetlet.2008.05.070,2008-05-17,0.6200607336197731
Tetrahedron,First asymmetric synthesis of (R)-desmethylsibutramine,,10.1016/s0040-4039(02)00297-6,2002-03-01,0.6200607336197731
Tetrahedron,Asymmetric synthesis of (R)-(−)-carnitine,,10.1016/s0040-4039(01)00780-8,2001-07-01,0.6200607336197731
Tetrahedron,Asymmetric synthesis of (−) (R) Yashabushiketol,,10.1016/s0040-4039(00)91579-x,1992-02-01,0.6200607336197731
Tetrahedron,An asymmetric synthesis of (+)-ocoteine,,10.1016/s0040-4039(00)84286-0,1986-01-01,0.6200607336197731
Tetrahedron,Asymmetric synthesis of L-cyclopentyl carbocyclic nucleosides,,10.1016/s0040-4039(97)00898-8,1997-06-01,0.6200607336197731
Tetrahedron,Organocatalytic asymmetric synthesis of quinine and quinidine,,10.1016/j.tetlet.2010.12.066,2010-12-22,0.6200607336197731
Tetrahedron,"An asymmetric synthesis of (2S,3S)-safingol",,10.1016/j.tetlet.2006.11.119,2006-12-15,0.6200607336197731
Tetrahedron,Asymmetric synthesis of (S)-camptothecin,,10.1016/s0040-4039(00)99086-5,1989-01-01,0.6200607336197731
Tetrahedron,Asymmetric synthesis of cytotoxic sponge metabolites R -strongylodiols A and B,,10.1016/j.tetlet.2004.05.122,2004-06-17,0.6200607336197731
Tetrahedron,"Asymmetric synthesis of (+)-L-733,060",,10.1016/j.tetlet.2004.12.025,2004-12-24,0.6200607336197731
Synthesis,Asymmetric Synthesis - The Essentials,,10.1055/s-2007-973641,2007-03-01,0.6200607336197731
Tetrahedron,"Asymmetric synthesis of sex pheromone of the western hemlock looper, Lambdina fiscellaria lugubrosa (Hulst)",,10.1016/j.tetlet.2023.154401,2023-02-06,0.6200607336197731
Tetrahedron,"The asymmetric synthesis of (2 S ,3 R )-capreomycidine",,10.1016/s0040-4039(01)00487-7,2001-05-01,0.6200607336197731
Tetrahedron,Asymmetric synthesis of (+)-chloriolide,,10.1016/j.tetlet.2010.03.028,2010-03-15,0.6200607336197731
Tetrahedron,Asymmetric synthesis of furofurans,,10.1016/j.tetlet.2017.11.011,2017-11-06,0.6200607336197731
Tetrahedron,Asymmetric synthesis of declines and hexahydroindanes,,10.1016/s0040-4039(00)89022-x,1990-01-01,0.6200607336197731
Tetrahedron,"Asymmetric synthesis of sceletium alkaloids: (−)-mesembrine, (+)-sceletium A-4, (+)-tortuosamine and (+)-N-formyltortuosamine",,10.1016/s0040-4039(98)01689-x,1998-10-01,0.6200607336197731
Tetrahedron,Asymmetric synthesis of the hydroxylamino sugar of calicheamicin,,10.1016/s0040-4039(00)73286-2,1994-07-01,0.6200607336197731
Organic Letters,Convergent and Enantioselective Total Synthesis of (−)-Amphidinolide O and (−)-Amphidinolide P,"A convergent and enantioselective total synthesis of (-)-amphidinolide O (1) and P (2), 15-membered macrolides with seven chiral centers along with many functional groups, is described. The key reactions include enantioselective Brown allylation, anti- and syn-selective aldol reactions, (E)-selective olefin metathesis, conformation-controlled stereoselective epoxidation, and selective introduction of the exomethylene group. Assignments of the absolute stereochemistries of the natural (+)-amphidinolide O (ent-1) and P (ent-2) are also discussed in detail.",10.1021/ol401357k,2013-06-24,0.620052764145918
Synthesis,"Stereo- and Regioselective Synthesis of 2-Amino-3,5-diols via Stereospecific Crotyl Transfer and Regioselective Aminohydroxylation","A short synthesis of 2-amino-3,5-diols is described, including the all- S isomer enigmol, a synthetic anticancer compound inspired by the structure of fumonisin B 1 . The synthetic route features 1) stereospecific crotyl transfer to tetradecanal via pericyclic oxonia-Cope rearrangement; 2) stereoselective epoxidation of the alkene; 3) regioselective epoxide opening with azide; and 4) reduction of azide to amine. This manuscript also corrects a structure assignment error in a previously reported synthesis of one of the diastereomers of enigmol.",10.1055/s-0032-1316805,2012-10-24,0.6200402887613726
Synlett,Asymmetric Synthesis of Ferrocenyl-2-thiazoline Ligands with C2-Symmetry,"The synthesis of previously unreported chiral ferrocene-thiazoline ligands is described. (S)-2-Azido-1-ferrocenylethanol, available by enantioselective reduction of α-azidoacetyl ferrocene was converted into the corresponding 5-ferrocenyl thiazoline by the three-step sequence: catalytic hydrogenation, acylation and cyclization promoted by Lawesson’s reagent. New chiral ferrocene-thiazolines with C2 symmetry were obtained when diacyl chlorides were used as acylating reagents.",10.1055/s-2002-20459,2002-01-01,0.6200369601683418
Organic Letters,Expedient Enantioselective Synthesis of the Δ<sup>4</sup>-Oxocene Cores of (+)-Laurencin and (+)-Prelaureatin,An expedient enantioselective synthesis of the Δ(4)-oxocene cores present in (+)-laurencin and (+)-prelaureatin was accomplished in eight steps via a novel one-pot regio- and stereoselective ring cyclization-fragmentation-expansion cascade from the tetrahydrofuran precursors which were prepared by stereocontrolled cyclization from vinylsilanes. This process is highlighted by an intramolecular oxo-carbenoid insertion and a β-silyl fragmentation sequence.,10.1021/ol1021965,2010-10-04,0.6200276740438088
Organic Letters,Total Stereoselective Synthesis of (+)-Goniothalesdiol,"[reaction: see text] The stereoselective synthesis of (+)-goniothalesdiol (1) was accomplished in nine steps starting from commercially available (-)-(2S,3S)-dimethyl D-tartrate (3). The key features were a completely diastereoselective reduction of a beta-ketosulfoxide to generate the stereogenic center at C-5 in 7 and formation of the 2,5-cis-substituted tetrahydrofuran ring in 10 from a stereoselective Et(3)SiH/TMSOTf-promoted reductive cyclization/deoxygenation.",10.1021/ol0523603,2005-11-01,0.6200276407651514
Tetrahedron,An elegant use of glycine for the synthesis of some novel β-lactams,,10.1016/s0040-4039(01)86120-7,1979-01-01,0.6199963777789941
Synlett,A New Synthesis of Tetrahydrofuran Fragment of Amphidinolides X and Y,A new synthesis of the tetrasubstituted tetrahydrofuran fragment of the marine secondary metabolites amphidinolides X and Y is described. The oxygenated chiral quaternary carbon was assembled by asymmetric dihydroxylation in high enantioselectivity and the tetrahydrofuran ring was constructed by an acid-catalyzed 5-endo ring-opening cyclization of the epoxide possessing a vinyl moiety.,10.1055/s-2006-932487,2006-03-10,0.6199941363476105
Tetrahedron,"New efficient protocol for aryne generation. Selective synthesis of differentially protected 1,4,5-naphthalenetriols",,10.1016/s0040-4039(00)93589-5,1991-11-01,0.6199941207773226
Journal of Organic Chemistry,Synthesis of Enantiopure 7-[3-Azidopropyl]indolizidin-2-one Amino Acid. A Constrained Mimic of the Peptide Backbone Geometry and Heteroatomic Side-Chain Functionality of the Ala-Lys Dipeptide,"Enantiopure N-(BOC)amino-7-[3-azidopropyl]indolizidin-2-one acid 1 has been synthesized by displacement of the methanesulfonate of its 7-hydroxypropyl counterpart 11 with sodium azide and subsequent ester hydrolysis. N-(BOC)Amino-7-[3-hydroxypropyl]indolizidin-2-one ester 11 was obtained from a sequence commencing with the alkylation of (2S,8S)-di-tert-butyl 5-oxo-2,8-di-[N-(PhF)amino]azelate 5 (PhF = 9-(9-phenylfluorenyl)). Stereoselective allylation of 5, regioselective olefin hydroboration, selective primary alcohol protection as a silyl ether, and oxidation of the secondary alcohol gave (2S,4R,8S)-di-tert-butyl 4-[3-tert-butyldimethylsiloxypropyl]-5-oxo-2,8-di-[N-(PhF)amino]azelate 9 as a pure diastereomer in 33% overall yield. Linear ketone 9 was then converted into the indolizidinone heterocycle by a route featuring reductive amination, lactam cyclization, and isolation by way of a silyl ether which provided the (6S,7R)-isomer of 11.",10.1021/jo001252l,2001-01-30,0.619992481993568
Organic Letters,"Total Synthesis and Biological Evaluation of 11-Desmethyllaulimalide, a Highly Potent Simplified Laulimalide Analogue","[reaction: see text] A step-economical synthesis of 11-desmethyllaulimalide (2) is reported. This simplified analogue is available through an improved second-generation synthetic approach to the laulimalides, in a shorter step count and from much less expensive starting material than the parent compound. This new lead retains the anticancer function of laulimalide.",10.1021/ol060233g,2006-03-01,0.6199814828618191
Journal of Organic Chemistry,"Reductive Oxy-Nazarov Cyclization toward Expedient Construction of a Cyclopenta[1,2-<i>b</i>]pyrrolo[1,2-<i>a</i>]azepine Ring System: Formal Total Syntheses of Stemonamine and Cephalotaxine","Formal total syntheses of stemonamine and cephalotaxine bearing the core cyclopenta[1,2- b ]pyrrolo[1,2- a ]azepine ring skeleton were achieved. The general synthetic strategy in the synthesis features the reductive oxy-Nazarov cyclization as key step, leading to the versatile construction of N-substituted spiro quaternary stereogenic centers from readily available starting materials.",10.1021/acs.joc.4c00035,2024-03-27,0.6199646290829445
Angewandte Chemie International Edition,Cover Picture: Synthesis of Cyclopamine Using a Biomimetic and Diastereoselective Approach (Angew. Chem. Int. Ed. 42/2009),"A biomimetic synthesis of the potent anticancer drug cyclopamine that features a CH activation/hydroxylation and a ring contraction/expansion is described by A. Giannis and co-workers in their Communication on page 7911 ff. The picture shows the structure of cyclopamine, the first inhibitor of hedgehog signaling (discovered in drosophilia); Veratrum californicum; a cyclopic sheep; and Homer, who first reported a cyclops in the Odyssey.",10.1002/anie.200904019,2009-09-03,0.6199641969825717
Tetrahedron,Studies towards the total synthesis of halichlorine: asymmetric synthesis of the spiroquinolizidine subunit,,10.1016/s0040-4039(99)01170-3,1999-09-01,0.6199515350497283
Organic Letters,Formal Total Synthesis of Spirangien A,A formal total synthesis of the spiroketal containing cytotoxic myxobacteria metabolite spirangien A (1) is described. The approach utilizes a late introduction of the C20 alcohol that mirrors the biosynthesis of this compound. The key steps involved a high yielding cross metathesis reaction between enone 6 and alkene 7 to give E-enone 4 and a Mn-catalyzed conjugate reduction α-oxidation reaction to introduce the C20 hydroxyl group. Acid treatment of the α-hydroxyketone 4 gave spiroketal 19 which was converted into known spirangien A (1) advanced intermediate spiroketal 3.,10.1021/ol3033253,2013-01-15,0.6199501576911502
Synlett,Stereoselective Synthesis of a Potent Human NK<sub>1</sub>Receptor Antagonist via Acyl-Claisen Rearrangement,Stereoselective synthesis of the tetrahydropyran derivative 1 is reported. Diastereoselective acyl-Claisen rearrangement was employed for formation of C3 and C4 chiral centres on the ­tetrahydropyran ring.,10.1055/s-2006-932489,2006-01-01,0.6199438786034772
Journal of Organic Chemistry,One-Pot Synthesis of Aminoenone via Direct Reaction of the Chloroalkyl Enone with NaN<sub>3</sub>: Rapid Access to Polycyclic Alkaloids,"A new one-pot procedure for the preparation of aminoenone from chloroalkyl enone and sodium azide was demonstrated. The structure of the presumed triazoline intermediate in this process was confirmed by X-ray analysis for the first time. As the application of this methodology, the synthesis of polycyclic alkaloid hexahydroapoerysopine (1a) was achieved through an efficient synthetic route.",10.1021/jo101226r,2010-07-16,0.6199431085408416
Journal of Organic Chemistry,"Total Synthesis of Racemic Benzomalvin E, a Quinazolinone Isolated from <i>Pencilium sp</i>. FN070315 and Exploration to the Direct Synthesis of (<i>E</i>)-Benzomalvin B","We present the first total synthesis of (±) benzomalvin E, featuring a quinazolino moiety with a 6–6–6–7-fused tetracyclic skeleton containing three nitrogen atoms. The key transformation involves Cu-catalyzed intramolecular C–N arylation of quinazolinone, leading to a sclerotigenin analogue that undergoes nucleophilic addition with benzaldehyde, enabling the synthesis of (±) benzomalvin E in six linear steps with a 33% overall yield. The (±) benzomalvin E’s structure was validated by 2-D NMR and single crystal XRD analysis and was further transformed into ( E )-benzomalvin B.",10.1021/acs.joc.3c02687,2024-02-13,0.6199302507566099
Organic Process Research & Development,"Correction to “Development of a Practical Telescoped Process to Prepare (<i>P</i>)-7-(2-Amino-6-fluorophenyl)-4-hydroxy-6-(trifluoromethyl)pyrido[3,4-<i>d</i>]pyrimidin-8(7<i>H</i>)-one: A Key Intermediate of KRAS<sup>G12C</sup> Inhibitor GH35”",,10.1021/acs.oprd.5c00106,2025-04-02,0.6199265847254016
Tetrahedron,Synthetic studies of withanolide I synthesis of ab ring moiety of withaferin A,,10.1016/s0040-4039(01)82508-9,1974-01-01,0.6199164679131166
Organic Letters,Asymmetric Total Synthesis of Clavolonine,The asymmetric total synthesis of clavolonine (1) has been achieved based on chiral auxiliary multiple-use methodology. Our synthetic route features stereoselective transformations on the cyclohexane ring utilizing the steric environment of the chiral auxiliary and an intramolecular Mannich reaction to construct the fused ring system.,10.1021/ol200376z,2011-03-09,0.6199162462928622
Organic Process Research & Development,Work-Up Optimization en Route to an Improved Process To Prepare a Progesterone Receptor Antagonist,"When the process to prepare nonsteroidal progesterone receptor antagonist 5 was scaled up, significant problems were encountered, and as a result lower than expected yields were obtained. In particular, the alkylation of pyrazole 2 with chloromethyl methyl sulfide failed to reach completion, and partial degradation of the product occurred during the work-up, resulting in a modest yield of alkylated pyrazole 3a . Further investigation has revealed the root cause of this problem, and an improved, robust process to 5 has been developed.",10.1021/op200145j,2011-06-28,0.6199096033079156
Organic Letters,A Short Synthesis of <i>Ergot</i> Alkaloids and Evaluation of the 5-HT<sub>1/2</sub> Receptor Selectivity of Lysergols and Isolysergols,"Key transformations in a four-step synthesis of the ergot alkaloid scaffold include a novel cesium carbonate-mediated hydrogen autotransfer alkylation to generate the C(3)–C(4) bond and an intramolecular Heck reaction that directly establishes the C(9)–C(10) alkene of methyl lysergate. An ester reduction and a streamlined experimental procedure establish a readily scalable, expedient total synthesis of all four stereoisomers of lysergol and isolysergol, including the previously unknown (−)-lysergol, for pharmacological evaluation at 5-HT 1A and 5HT 2A,B,C receptors. A bicyclic scaffold is also characterized for the first time in the intramolecular Heck coupling.",10.1021/acs.orglett.2c02569,2022-08-22,0.6198684126224004
Synthesis,A Practical and Cost-Effective Synthesis of d-erythro-Sphingosine from d-ribo-Phytosphingosine via a Cyclic Sulfate Intermediate,"The practical and efficient synthesis of d-erythro-sphingosine from commercially available d-ribo-phytosphingosine is described­. An important feature of this synthesis is the selective transformation of the 3,4-vicinal diol of phytosphingosine into the characteristic E-allylic alcohol of sphingosine via a cyclic sulfate intermediate that contains a non-nucleophilic trifluoroacetamide protecting group.",10.1055/s-0030-1258437,2011-02-10,0.6198606999591755
Journal of the American Chemical Society,The Total Synthesis of Eleutherobin,"The total synthesis of the title compound ( 1 ), starting with ( R )-(−)-α-phellandrene ( 6 ), has been accomplished. The synthesis rigorously proves the relative stereochemical relationship of the diterpenoid and carbohydrate domains of eleutherobin. Key reactions included a Nozaki−Kishi ring closure to produce a furanophane (see 37 → 38 ), a pyranose to furanose transposition (see 50 → 47 ), and a novel oxycarbaglycosidation (cf. 58 → 87 ) for joining the two domains.",10.1021/ja990215c,1999-06-30,0.6198419914248541
Journal of Organic Chemistry,Modular Synthesis of Di- and Trisubstituted Imidazoles from Ketones and Aldehydes: A Route to Kinase Inhibitors,"High Resolution Image Download MS PowerPoint Slide A one-pot and modular approach to the synthesis of 2,4(5)-disubstituted imidazoles was developed based on ketone oxidation, employing catalytic HBr and DMSO, followed by imidazole condensation with aldehydes. This methodology afforded twenty-nine disubstituted NH -imidazoles (23%–85% yield). A three-step synthesis of 20 kinase inhibitors was achieved by employing this oxidation–condensation protocol, followed by bromination and Suzuki coupling in the imidazole ring to yield trisubstituted NH -imidazoles (23%–69%, three steps). This approach was also employed in the synthesis of known inhibitor GSK3037619A.",10.1021/acs.joc.9b01844,2019-08-28,0.6198390202455871
Journal of Organic Chemistry,"Asymmetric Synthesis of 1,2,9,9a-Tetrahydrocyclopropa[<i>c</i>]benzo[<i>e</i>]indol-4-one (CBI)","A short, asymmetric synthesis of the 1,2,9,9a-tetrahydrocyclopropa[c]benzo[e]indol-4-one (CBI) analogue of the CC-1065 and duocarmycin DNA alkylation subunits is described. Treatment of iodo-epoxide 5, prepared by late-stage alkylation of 4 with (S)-glycidal-3-nosylate, with EtMgBr at room temperature directly provides the optically pure alcohol 6 in 87% yield (99% ee) derived from selective metal-halogen exchange and subsequent regioselective intramolecular 6-endo-tet cyclization. The use of MeMgBr or i-PrMgBr also provides the product in high yields (82-87%), but requires larger amounts of the Grignard reagent to effect metal-halogen exchange and cyclization. Direct transannular spirocyclization of 7 following O-debenzylation of 6 provides N-Boc-CBI. This approach represents the most efficient (9-steps, 31% overall) and effective (99% ee) route to the optically pure CBI alkylation subunit yet described.",10.1021/jo102136w,2010-12-30,0.6198381137501906
Angewandte Chemie International Edition,"Short and Divergent Total Synthesis of (+)‐Machaeriol B, (+)‐Machaeriol D, (+)‐Δ<sup>8</sup>‐THC, and Analogues","Short and highly efficient stereoselective syntheses provide machaeriols and cannabinoids in a divergent approach starting from a common precursor, commercially available (S)-perillic acid. Key features of the novel strategy are a stereospecific palladium-catalyzed decarboxylative arylation and a one-pot sequence comprising a stereoselective hydroboration followed by oxidation or reduction of the corresponding intermediary boranes. The divergent approach is convincingly demonstrated by the five-step syntheses of (+)-machaeriol B, (+)-machaeriol D, and related analogues, and the four-step synthesis of (+)-Δ(8)-THC and an analogue.",10.1002/anie.201502595,2015-06-16,0.6198164189082482
Tetrahedron,A novel synthesis of 4′-thionucleosides and a potential stereospecific route to pyrimidine nucleosides,,10.1016/s0040-4039(00)01796-2,2000-12-01,0.6198123807093815
Organic Letters,Enantioselective Total Synthesis and Structure Revision of Spirodihydrobenzofuranlactam 1. Total Synthesis of Stachybotrylactam,[reaction: see text] The enantioselective total synthesis and structure revision of spirodihydrobenzofuranlactam 1 and of its regioisomer 25 are presented. Optically pure (+)-Wieland-Miescher ketone was utilized to construct the AB bicyclic core in 10 steps. Introduction of the resorcylate D-ring unit was achieved by use of our tert-butyl ester metalation sequence. Subsequent stereoselective spirocyclization to form the C-ring was followed by regioselective ring cyanation and lactam formation to produce the pentacyclic structure 1 and its regioisomer 25.,10.1021/ol030039j,2003-04-19,0.6198072691499201
Journal of Organic Chemistry,Studies on the Synthesis of Apoptolidin A. 1. Synthesis of the C(1)−C(11) Fragment,A synthesis of the C(1)-C(11) fragment of apoptolidin A has been accomplished by a convergent route involving the stereoselective glycosidation of 9 and the Suzuki cross-coupling reaction of bromodienoate 7 and the vinylborane generated via chemoselective hydroboration of diyne 6 with diisopinocampheylborane.,10.1021/jo702250z,2007-12-29,0.6198030399003601
Journal of the American Chemical Society,Enantioselective Total Synthesis of (+)-Stephadiamine,"An asymmetric synthesis of (+)-stephadiamine has been accomplished featuring (a) an enantioselective dearomatizative Michael addition to generate a quaternary stereocenter; (b) a domino sequence involving reductive generation of nitrone from γ-nitro ketone followed by a highly regio- and diastereo-selective intramolecular [3 + 2] cycloaddition to construct the aza[4,3,3]propellane core with concurrent generation of two quaternary stereocenters and two functional groups ready for subsequent transformations; (c) the Curtius rearrangement of the sensitive α,α-disubstituted malonic acid mono ester for the installation of α,α-disubstituted amino ester moiety; (d) a benzylic C-H oxidation under photoredox catalytic conditions; and (e) a highly diastereoselective ketone reduction affording δ-hydroxyester preorganized for lactonization.",10.1021/jacs.3c00884,2023-02-27,0.6198027195488142
Synthesis,Stereoselective Synthesis of the C10-C18 Fragment of Iriomoteolide-3a,An efficient synthesis of the highly stereogenic centered C10–C18 fragment of iriomoteolide-3a has been accomplished. Key steps include Sharpless asymmetric dihydroxylation and epoxidation for generation of the desired stereocenters.,10.1055/s-0032-1318141,2013-02-07,0.6197751166186467
Tetrahedron,Synthesis of geiparvarin: a novel antitumor agent possessing a 3(2H)-furanone ring,,10.1016/s0040-4039(00)71453-5,1980-01-01,0.6197739725844688
Organic Process Research & Development,An Efficient Synthesis of Tenofovir (PMPA): A Key Intermediate Leading to Tenofovir-Based HIV Medicines,"Herein, we report further improvements to the synthesis of tenofovir 1, the precursor to tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide fumarate (TAF). Starting from acyclic precursor diaminomalononitrile 12, a four-step protocol to tenofovir 1 will allow for vertical integration for more manufacturers. The key transformation is a convergent one-step procedure from 6 as compared to the current commercial process, with an improved yield from 59% (two steps) to 70%. Further improvements include eliminating the need for problematic magnesium tert -butoxide (MTB) and significant solvent reduction by avoiding an intermediate workup. With the costs of HIV/AIDS treatments remaining a barrier for those most in need, lowering the raw material/processing costs and increasing the security of supply can increase patient access.",10.1021/acs.oprd.0c00078,2020-05-29,0.6197704438617018
Tetrahedron,"An efficient and versatile route to the synthesis of 9,10-dihydro-3-formylphenanthrenes",,10.1016/j.tetlet.2007.01.049,2007-01-15,0.619766767193202
Journal of Organic Chemistry,A Formal Total Synthesis of (±)-Kopsihainanine A Using a Raney-Cobalt Mediated Reductive Cyclization Route to Polyhydroquinolines,"Perhydroquinoline 4, the product of a Raney-cobalt mediated reductive cyclization reaction, was readily converted into the cis-ring-fused perhydroquinoline 15 that could be epimerized to its trans-fused counterpart 2 on sequential treatment with iodosylbenzene then sodium borohydride. Tetracycle 2 is an advanced intermediate associated with a recently reported total synthesis of the alkaloid kopsihainanine A (1).",10.1021/acs.joc.6b01400,2016-07-15,0.6197624959139159
Synlett,An Expeditious Route to 3-Formylfuran,"All articles of this category An expeditious route to 3-formylfuran from cis -2-butene-1,4-diol has been developed in 42% overall yield in a sequence of five-stage transformations. 3-formylfuran - NBS - dihydro-1,3-dioxepine - ”dihydro-1,3-dioxepin-tetrahydrofuran rearrangement bromo-etherification - cis -2-butene-1,4-diol",10.1055/s-1995-4915,1995-02-01,0.619760550598417
Organic Letters,Toward the Second Generation Synthesis of Aplyronine A: Stereocontrolled Assembly of the C1−C19 Segment by Using an Asymmetric Nozaki−Hiyama−Kishi Coupling,An efficient synthesis of the C1-C19 segment of aplyronine A is described. Stereoselective construction of the C14-C15 (E)-trisubstituted double bond and the C13 stereocenter was achieved by using an asymmetric Nozaki-Hiyama-Kishi coupling.,10.1021/ol1029657,2011-01-26,0.6197280256738356
Organic Letters,Short Asymmetric Synthesis of (−)- and (+)-<i>cis</i>-Lauthisan,"The asymmetric synthesis of both enantiomers of cis-lauthisan (3) is achieved in only six steps from diethyl pimelate (4), the key steps being the diastereodivergent reduction of beta-ketosulfoxide 7 and the highly cis-stereoselective Et(3)SiH/TMSOTf-promoted reductive cyclization of enantiopure hydroxy sulfinyl ketones (S)-14 and (R)-14.",10.1021/ol050620a,2005-04-19,0.6197256039289621
Journal of Organic Chemistry,Construction of the Tricyclic 5−7−6 Scaffold of Fungi-Derived Diterpenoids. Total Synthesis of (±)-Heptemerone G and an Approach to Danishefsky’s Intermediate for Guanacastepene A Synthesis,"An efficient and operationally simple synthesis of the neodolestane diterpenoids (±)-heptemerone G and (±)-guanacastepene A is reported. The common tricyclic scaffold (±)-4 was prepared from 2-methylcyclopent-2-en-1-one via 23 isolated intermediates in 5.1% yield. The key features include a novel annulation sequence combining tandem conjugate addition, methylenation, and metathesis reaction and completely diastereoselective transformation of the azulene derivative 23 into rings AB building block 32. Stereochemistry of alkylation of both saturated trans-azulene enolate 38 and its α,β-unsaturated counterpart 48 was examined. Rather surprisingly, a different facial selectivity was recorded. Several synthetic methods were modified or developed, including an alternative methodology for the Wharton-type rearrangement, ketalization of epimerizable ketone under mild conditions, and efficient alkylation of a ketone via its kinetic enolate.",10.1021/jo101758t,2010-11-17,0.6197134095542726
Organic Letters,Total Syntheses of the Dihydrofuranonecarboxylate Natural Products Gregatin B and E: Gram-Scale Synthesis of (+)-Gregatin B and Unambiguous Assignment of the Stereostructure of (+)-Gregatin E,"We synthesized the dextrorotatory enantiomers of gregatin B (1.3 g scale) and E, establishing their diene side chains in the last step by Heck coupling with variable iodoolefins. Their counterpart was synthesized in 30% overall yield and with high enantiopurity (97% ee) from benzyl tiglate, beginning with an asymmetric dihydroxylation. The stereostructure of gregatin E followed from HPLC comparisons between the four synthetic stereoisomers of this compound and natural gregatin E, which we isolated from Cadophora gregata.",10.1021/ol5032602,2014-12-08,0.6197121558884815
Tetrahedron,Periplanone total synthesis via intramolecular pinacol coupling,"We have carried out an enantioselective synthesis of (-)-periplanone C by a route involving titanium-induced, intramolecular pinacol coupling reaction of a 1,10 keto aldehyde as the key step. The coupling occurs with predictable stereochemistry to give a mixture of two diol products in greater than 60% yield.",10.1016/s0040-4039(00)60712-8,1994-06-01,0.6197119522096923
Synlett,Synthesis of (±)-Crotomachlin,"All articles of this category An efficient synthesis of ( ± )-crotomachlin ( 1 ) was accomplished starting from 4,4,10-trimethyl-9-methylene-Δ 6 -8-octalone ( 4 ) in 7 steps. crotomachlin - diterpene - antilipoxygenase activity - 3-methylsulfolene - pyrolysis",10.1055/s-1996-5358,1996-02-01,0.6197074514785972
Synlett,"Efficient Chiral Route to a Key Building Block of 1,25-Dihydroxyvitamin D<sub>3</sub>via Lipase-Mediated Resolution","All articles of this category Racemic ethyl 5-hydroxy-1-cyclopentenecarboxylate [(±)- 4 ] was resolved with complete enantiospecificity via kinetic acetylation in tert -butyl methyl ether in the presence of lipase PS which furnished optically pure ( R )-acetate [( R )- 5 ] and ( S )-alcohol [( S )- 4 ] both in nearly quantitative yields after silica gel column chromatography. ( R )-Alcohol [( R )- 4 ] obtained from ( R )- 5 was transformed into 1-ethynylbicyclo[3.1.0]hexan-2-one ( 3 ), a key building block of 1,25-dihydroxyvitamin D 3 ( 1 ), in eight steps in 30% overall yield.",10.1055/s-1992-21362,1992-01-01,0.6197053609017086
Organic Letters,Total Synthesis of (+)-Laurencin:  An Asymmetric Alkylation−Ring-Closing Metathesis Approach to Medium Ring Ethers,[formula: see text] The enantioselective total synthesis of (+)-laurencin 1 is achieved in 18 steps from (S)-(+)-4-benzyl-3-benzyloxyacetyl-2-oxazolidinone. The key steps in this synthesis are an asymmetric glycolate alkylation leading to acyl oxazolidinone 2 and a subsequent ring-closing olefin metathesis to construct the oxocene core of 1. The approach to medium ring ethers utilized in this synthesis provides a general and efficient route to the cyclic core of other marine natural products.,10.1021/ol991201e,1999-11-16,0.6197007934613714
Organic Letters,Enantioselective Total Synthesis of Cannogenol-3-<i>O</i>-α-<scp>l</scp>-rhamnoside via Sequential Cu(II)-Catalyzed Michael Addition/Intramolecular Aldol Cyclization Reactions,"A concise and scalable enantioselective total synthesis of the natural cardenolides cannogenol and cannogenol-3-O-α-l-rhamnoside has been achieved in 18 linear steps. The synthesis features a Cu(II)-catalyzed enantioselective and diastereoselective Michael reaction/tandem aldol cyclization and a one-pot reduction/transposition, which resulted in a rapid (6 linear steps) assembly of a functionalized intermediate containing C19 oxygenation that could be elaborated to cardenolide cannogenol. In addition, a strategy for achieving regio- and stereoselective glycosylation at the C3 position of synthetic cannogenol was developed and applied to the preparation of cannogenol-3-O-α-l-rhamnoside.",10.1021/acs.orglett.7b03513,2017-12-15,0.6196946122418491
Organic Letters,Asymmetric Total Synthesis of (−)-Leuconoxine via Chiral Phosphoric Acid Catalyzed Desymmetrization of a Prochiral Diester,The asymmetric total synthesis of (-)-leuconoxine has been achieved. The desymmetrization of a prochiral diester using a chiral phosphoric acid catalyst produced a highly enantioenriched lactam with excellent yield. The ring construction featuring an intramolecular N-acyliminium cyclization and the one-step pyrrolidone formation using Bestmann's ylide was successfully accomplished.,10.1021/ol5033865,2014-12-19,0.6196869104930769
Tetrahedron,New highly conjugated porphyrin chromophores: Synthesis of mono- and diphenanthroporphyrins,,10.1016/0040-4039(95)00818-w,1995-06-01,0.6196836919159012
Tetrahedron,"A novel route to cumulenes. The addition of dihalocarbenes to 2,5-dimethyl-2,3,4-hexatriene.",,10.1016/s0040-4039(00)90174-6,1965-01-01,0.6196529173067524
Tetrahedron,Reductive cyclization of indolic imides - a new β-carboline synthesis,,10.1016/s0040-4039(01)83437-7,1977-01-01,0.6196477879094149
Tetrahedron,"New synthetic route to the alkaloid withasomnine by ring transformation of a functionalized cyclopropanol via the parent pyrrolo[1,2-b]pyrazole",,10.1016/0040-4039(95)02313-5,1996-02-01,0.6196472673246043
Journal of Organic Chemistry,"Total Syntheses of the <i>Securinega</i> Alkaloids (+)-14,15-Dihydronorsecurinine, (−)-Norsecurinine, and Phyllanthine","A new strategy for enantiospecific construction of the Securinega alkaloids has been developed and applied in total syntheses of (+)-14,15-dihydronorsecurinine (8), (-)-norsecurinine (6), and phyllanthine (2). The B-ring and C7 absolute stereochemistry of these biologically active alkaloids originated from trans-4-hydroxy-L-proline (10), which was converted to ketonitrile 13 via a high-yielding eight-step sequence. Treatment of this ketonitrile with SmI2 afforded the 6-azabicyclo[3.2.1]octane B/C-ring system 14, which is a key advanced intermediate for all three synthetic targets. Annulation of the A-ring of (-)-norsecurinine (6) with the required C2 configuration via an N-acyliminium ion alkylation was accomplished using radical-based amide oxidation methodology developed in these laboratories as a key step, providing tricycle 33. Annulation of the D-ring onto alpha-hydroxyketone 33 with the Bestmann ylide 45 at 12 kbar gave (+)-14,15-dihydronorsecurinine (8). In the securinine series, the D-ring was incorporated using an intramolecular Wadsworth-Horner-Emmons olefination of phenylselenylated alpha-hydroxyketone 47. The C14,15 unsaturation was installed late in the synthesis by an oxidative elimination of the selenoxide derived from tetracyclic butenolide 50 to give (-)-norsecurinine (6). The A-ring of phyllanthine (2) was formed from hydroxyketone 14 using a stereoselective Yb(OTf)3-promoted hetero Diels-Alder reaction of the derived imine 34 with Danishefsky's diene, affording adduct 35. Conjugate reduction and stereoselective equatorial ketone reduction of vinylogous amide 35 provided tricyclic intermediate 36, which could then be elaborated in a few steps to stable hydroxyenone 53 via alpha-selenophenylenone intermediate 52. The D-ring was then constructed, again using an intramolecular Wadsworth-Horner-Emmons olefination reaction to give phyllanthine (2).",10.1021/jo000260z,2000-07-13,0.6196234516664444
Organic Process Research & Development,Early Process Development and Scale-Up of Orally Active Apomorphine Drug Candidates,"The manufacturing route to a novel apomorphine Parkinson’s drug candidate (MCL-509) has been developed from a mg laboratory scale to that suitable for use on a 20–50 L scale. While the synthetic sequence could not be bettered, all six reaction steps required significant improvement for scale-up. Hazardous and toxic reagents and hazardous steps were removed; all concentrations to dryness and chromatographic purifications were eliminated; isolations were operationally simplified, and plant cycle times were shortened. Two pairs of steps (1 and 2; 5 and 6) were successfully telescoped, and steps 3, 4, and 5 were re-imagined such that all three steps were substantially redeveloped with alternative reagents. Now relying solely on crystallizations for isolation, the yield, purity, and color of each intermediate was greatly improved. All six process steps were easily transferred to the pilot plant with only minimal accommodation work required prior to manufacture on a 20–50 L scale per batch. Thus, the manufacturing campaign performed essentially as expected and without issues while delivering an approximate 10-fold increase in material yield alongside the requisite quality improvements.",10.1021/acs.oprd.2c00297,2022-12-12,0.6196224631991419
Journal of Organic Chemistry,Total Synthesis of Rucaparib,"A concise total synthesis of rucaparib, an FDA-approved drug for ovarian and prostate cancers, is reported. The Heck reaction of the commercially available aryl iodide with acrylonitrile provided the desired ( E )-2-aminocinnamonitrile derivative. A subsequent imino-Stetter reaction of the aldimine derived from 2-aminocinnamonitrile and aldehyde furnished indole-3-acetonitrile bearing the desired substituents at appropriate positions. The construction of the final azepinone scaffold via reduction of the nitrile group followed by seven-membered lactamization afforded rucaparib. Notably, the synthesis of rucaparib is achieved using commercially available starting materials in only three separation operations with 54% overall yield.",10.1021/acs.joc.2c00083,2022-03-23,0.6196077310077536
Journal of Organic Chemistry,Synthesis of Coprinol and Several Alcyopterosin Sesquiterpenes by Regioselective [2 + 2 + 2] Alkyne Cyclotrimerization,"Alkyne [2 + 2 + 2] cyclotrimerization is a strategically attractive but tactically challenging approach to the synthesis of highly substituted benzene rings. Here, a bimolecular regioselective cyclotrimerization is applied to the total synthesis of the natural product coprinol and several related alcyopterosins from the illudalane family of sesquiterpenes. The synthesis of coprinol from dimedone was completed in six steps and a 57% overall yield. Alternative functional group manipulations lead to alcyopterosins A, B, and O and two additional congeners, all within six steps.",10.1021/acs.joc.2c01741,2022-10-10,0.6195927737594558
Synthesis,"An Improved Synthesis of 2,3-Diamino-5,6-dichloropyrazine: A Useful Heterocyclic Scaffold","Abstract 2,3-Diamino-5,6-dichloropyrazine represents a valuable but underexplored heterocyclic building block. Due to the use of harsh conditions and lack of selectivity surrounding the known literature synthesis, we developed a more accessible and selective three-step route from 2-aminopyrazine. Challenging conditions are avoided by using a high-yielding dichlorination with N-chlorosuccinimide (NCS), which is followed by a regioselective amination. The installation of the last chlorine atom using 1-chloro-1,2-benziodoxol-3(1H)-one is rapid, enabling access to 2,3-diamino-5,6-dichloropyrazine in an improved overall yield (41%).",10.1055/s-0043-1775410,2024-10-14,0.6195887975586819
Journal of Organic Chemistry,Synthesis and Kinetic Analysis of the <i>N</i>-Acetylhexosaminidase Inhibitor XylNAc-Isofagomine,"[reaction: see text] An efficient 10-step preparation from 4-methoxypyridine of (2R,3R,4R)-2-acetamido-3,4-dihydroxypiperidine (""XylNAc-isofagomine"") in optically active form is described. Key steps include an enantioselective reduction with catecholborane/(S)-2-methyl-CBS-oxazaborolidine, and a stereoselective pseudo-glycosylation of lithium azide by a cyclic sulfite ester. The title compound showed a Ki = 21 microM when evaluated against the N-acetyl-beta-hexosaminidase from Streptomyces plicatus.",10.1021/jo051117e,2005-08-09,0.6195856479397663
Synthesis,Methylenomycin B: A New Synthesis from a β-Ketophosphonate,"All articles of this category Methylenomycin B ( 1 ) was prepared from diethyl 2-oxopropanephosphonate ( 5 ) in four steps in 26% yield. The key steps in this synthesis include the Wittig-Horner reaction of 5 with methylthioethanal ( 7 ) followed by the 1,4-addition of a propionyl anion equivalent to the α-enone 4 formed affording 4-(methylthiomethyl)-hepta-2,5-dione ( 3 ) which is an acyclic precursor of the title antibiotic.",10.1055/s-1987-28041,1987-01-01,0.6195826421696318
Journal of the American Chemical Society,"Synthesis of Chiral Chromans by the Pd-Catalyzed Asymmetric Allylic Alkylation (AAA):  Scope, Mechanism, and Applications","The Pd-catalyzed asymmetric allylic alkylation (AAA) of phenol allyl carbonates serves as an efficient strategy to construct the allylic C-O bond allowing access to chiral chromans in up to 98% ee. The effect of pH and the influence of olefin geometry, as well as substitution pattern on the ee and the absolute configuration of the chiral chromans were explored in detail. These observations suggest a mechanism involving the cyclization of the more reactive pi-allyl palladium diastereomeric intermediate as the enantiodiscriminating step (Curtin-Hammett conditions). This methodology led to the enantioselective synthesis of the vitamin E core, the first enantioselective total synthesis of (+)-clusifoliol and (-)-siccanin, and the synthesis of an advanced intermediate toward (+)-rhododaurichromanic acid A.",10.1021/ja048078t,2004-09-01,0.6195746450585327
Organic Process Research & Development,A Second Generation Synthesis of Benzyl Piperidine Derivatives: A Key Intermediate for the Preparation of SERT/5-HT<sub>1A</sub> Dual Inhibitor,"A second generation process for benzyl piperidine 10 is described. By the use of a Horner–Wadsworth–Emmons reaction and selective hydrogenation with Pt/C in ethyl acetate, 2-bromo-5-(hydroxymethyl) phenol 14 was efficiently converted to the compound 10 on a 5 kg scale. A small amount of water was found to be critical to complete the selective hydrogenation with low levels of debrominated byproduct 15 . Impurities of the compound 10 were controlled by limiting the quality of 2-bromo-5-(hydroxymethyl) phenol 14 and 1-bromo-2-methoxyethane 15 .",10.1021/acs.oprd.5b00207,2015-08-12,0.6195414246432975
Synlett,"New Approach to Flavonols via Base-Mediated Cyclization: Total Synthesis of 3,5,6,7-Tetramethoxyflavone","A new methodology for the synthesis of flavonols is described. The key step is a base-mediated cyclization-isomerization-elimination reaction which results in the formation of flavonols. Using this strategy, three flavonols are synthesized and characterized.",10.1055/s-0031-1290207,2012-01-26,0.6195376148090792
Organic Letters,Total Synthesis of Cladoniamide G,"The total synthesis of cladoniamide G, a cytotoxic compound against MCF-7 breast cancer cells (10 μg/mL), was accomplished. Key steps in the sequence include oxidative dimerization of 3-acetoxy-5-chloroindole and a tandem process incorporating three steps: bimolecular carbonyl addition, lactam formation, and carbamate removal.",10.1021/ol400055v,2013-02-15,0.6195268346525963
Organic Process Research & Development,Manufacturing Process Development of Tegoprazan as a Potassium-Competitive Acid Blocker (P-CAB),"Tegoprazan, a selective potassium-competitive acid blocker, was approved in 2018 in the Republic of Korea for the treatment of gastroesophageal reflux disease (GERD), erosive esophagitis (EE), and nonerosive reflux disease (NERD). The complexity of tegoprazan, which contains a 4,6-disubstituted 1 H -benzo[ d ]imidazole core and a chiral chromanol moiety, makes it a challenging molecule to prepare on a commercial scale. An efficient and economical route of the key intermediates and a much improved end-game for tegoprazan were developed.",10.1021/acs.oprd.4c00005,2024-03-08,0.6195236443963721
Journal of Organic Chemistry,Total Synthesis of Cortistatins A and J,"This paper describes the details of our synthetic studies on the marine steroidal alkaloids cortistatins A and J. The key features of our strategy include (i) an efficient Knoevenagel/electrocyclic strategy to couple the diketone and the CD-ring fragment, (ii) a chemoselective radical cyclization to construct the oxabicyclo[3.2.1]octene B-ring system, (iii) a highly stereocontrolled installation of the isoquinoline unit, and (iv) a late-stage functionalization of the A-ring.",10.1021/jo2002616,2011-03-15,0.6195076443333436
Journal of Organic Chemistry,A Rapid and Efficient Sonogashira Protocol and Improved Synthesis of Free Fatty Acid 1 (FFA1) Receptor Agonists,"A protocol for rapid and efficient Pd/Cu-catalyzed coupling of aryl bromides and iodides to terminal alkynes has been developed with use of 2-(di-tert-butylphosphino)-N-phenylindole (cataCXium PIntB) as ligand in TMEDA and water. The new protocol successfully couples substrates which failed with standard Sonogashira conditions, and enables an efficient general synthetic route to free fatty acid 1 (FFA1) receptor ligands from 3-(4-bromophenyl)propionic acid.",10.1021/jo902533p,2010-01-25,0.6195054843023596
Angewandte Chemie International Edition,Total Synthesis of Rapamycin,Rapamycin synthesis all wrapped up: A new convergent synthesis of rapamycin (1) is reported that involves a macroetherification/catechol tethering strategy for construction of the macrocyclic core of this intriguing natural product. Other studies on this commercialized potent immunosuppressant delineate new cell signaling pathways of relevance to cancer chemotherapy.,10.1002/anie.200604053,2006-12-08,0.6195038023274247
Synthesis,"A Scalable, Chromatography-Free Synthesis of Benzotetramisole","The scalable, chromatography-free synthesis of the chiral isothiourea benzotetramisole (BTM) in two steps from commercially available materials is presented. A detailed procedure for the synthesis of both enantiomers and the racemate on ca. 10 gram scale is disclosed.",10.1055/s-0034-1378931,2014-11-21,0.6194930195445152
Tetrahedron,A new route towards the synthesis of substituted naphthalenes via Friedel–Crafts acylation,,10.1016/s0040-4039(00)00145-3,2000-03-01,0.6194885631944006
Tetrahedron,Synthesis of deoxophylloerythroetioporphyrin (DPEP) and three ring homologs by an improved b-bilene methodology,,10.1016/s0040-4039(98)01960-1,1998-11-01,0.6194862580244318
Journal of the American Chemical Society,Total Synthesis of Chloropeptin II (Complestatin) and Chloropeptin I,"The first total synthesis of chloropeptin II (1, complestatin) is disclosed. Key elements of the approach include the use of an intramolecular Larock indole synthesis for the initial macrocyclization, adopting conditions that permit utilization of a 2-bromoaniline, incorporating a terminal alkyne substituent (-SiEt(3)) that sterically dictates the indole cyclization regioselectivity, and benefiting from an aniline protecting group (-Ac) that enhances the atropdiastereoselectivity and diminishes the strained indole reactivity toward subsequent electrophilic reagents. Not only did this key reaction provide the fully functionalized right-hand ring system of 1 in superb conversion (89%) and good atropdiastereoselectivity (4:1 R:S), but it also represents the first reported example of what will prove to be a useful Larock macrocyclization strategy. Subsequent introduction of the left-hand ring system enlisting an aromatic nucleophilic substitution reaction for macrocyclization with biaryl ether formation completed the assemblage of the core bicyclic structure of 1. Intrinsic in the design of the approach and by virtue of the single-step acid-catalyzed conversion of chloropeptin II (1) to chloropeptin I (2), the route also provides a total synthesis of 2.",10.1021/ja907193b,2009-10-19,0.6194782481341027
Journal of Organic Chemistry,Total Synthesis of (−)-Solanapyrone A via Enzymatic Diels−Alder Reaction of Prosolanapyrone,"The syntheses of prosolanapyrones I ( 6 ) and II ( 7 ) via the aldol reactions of pyrone and dienal segments have been achieved in five steps in 31% overall yield for 6 and seven steps in 5% overall yield for 7 . An improved synthetic route starting from vinylpyrone 27 provided 7 in 11 steps in 12% overall yield. The enzymatic Diels−Alder reaction of 7 affords (−)-solanapyrone A ( 1 ) with high enantioselectivity and with good exo-selectivity, which is difficult to attain by chemical methods. In addition, a crude enzyme preparation from Alternaria solani has been used to perform a kinetic resolution of (±)- 3 .",10.1021/jo980743r,1998-11-01,0.6194656342809478
European Journal of Organic Chemistry,One‐Pot Two‐Step Synthesis of Isochromene‐Fused CF<sub>3</sub>‐Substituted Pyrazoles,"An efficient one‐pot, two step method for fusing two biologically active motifs, CF 3 ‐substituted pyrazoles and isochromenes, was developed. Selective O ‐benzylation of CF 3 ‐substituted pyrazolones and subsequent Pd‐catalyzed direct C–H arylation generate a fused tricycle. For the synthesized compounds through‐space 13 C– 19 F spin–spin coupling was revealed. In addition, the synthesis of three thioisochromene analogues, and one isocoumarin derivative, was accomplished.",10.1002/ejoc.202000942,2020-07-23,0.619464206756298
Journal of Organic Chemistry,Scalable Total Synthesis of (+)-Desmethylxestospongin B,"Herein, the execution of synthetic strategies solving scalability issues observed in the original route is reported, increasing the total yield by 50% compared to the previously disclosed synthesis. A notable restructuring of the route's initial steps to reach a common allylic alcohol intermediate employs a highly stereoselective epoxidation method and avoids superfluous protecting group manipulations while limiting dependence on kinetic resolution in establishing stereochemistry for four of the six chiral centers in (+)-desmethylxestospongin B. Different protecting group strategies to avoid problems with their subsequent removal were considered and enacted; to this end, material was retained as byproducts were suppressed. While the lactam semireduction under Birch conditions requires further investigation, the updated synthesis of (+)-desmethylxestospongin B reported here made it more scalable, affording 0.37 g of this natural product for continued biological studies.",10.1021/acs.joc.4c00779,2024-05-29,0.6194586806138662
Organic Letters,Novel Alternative for the N<i>−</i>S Bond Formation and Its Application to the Synthesis of Benzisothiazol-3-ones,"[reaction: see text] The synthesis of a series of benzisothiazolone derivatives starting from the readily available methyl thiosalicylate is presented. The key cyclization step features the formation of a N-acylnitrenium ion, generated by the hypervalent iodine reagent PIFA, and its succeeding intramolecular trapping by the thiole moiety leading to the construction of the title compounds by formation of a new N-S bond.",10.1021/ol061867q,2006-09-15,0.6194496104904343
Angewandte Chemie International Edition,"Adenophorone, An Unprecedented Sesquiterpene from <i>Eupatorium adenophorum</i>: Structural Elucidation, Bioinspired Total Synthesis and Neuroprotective Activity Evaluation","Abstract (−)‐Adenophorone ( 1 ), a caged polycyclic sesquiterpene featuring an unprecedented tricyclo[4.3.1.0 5,9 ]decane skeleton, was isolated from Eupatorium adenopharum Spreng. The structure of 1 was unambiguously established by a combination of spectroscopic analysis, X‐ray crystallography, and bioinspired total synthesis. Key synthetic features include a sequential Reformatsky/oxidation/regio‐ and stereoselective hydrogenation, and subsequent merged MBH–Tsuji–Trost cyclization. The concise synthetic sequence efficiently constructs the bicyclic skeleton of cadinene sesquiterpene (+)‐euptox A ( 2 ) in 8 steps from commercially available monoterpene (−)‐carvone ( 6 ), with outstanding performance on diastereocontrol. The bioinspired synthesis of 1 was achieved from 2 , a plausible biogenetic precursor, via transannular Michael addition. This work provides experimental evidence of our proposed biosynthetic hypothesis of 1 . Additionally, compound 1 showed potent neuroprotective activity in H 2 O 2 ‐treated SH‐SY5Y and PC12 cells.",10.1002/anie.202306326,2023-06-07,0.6194378056683689
Angewandte Chemie International Edition,Rational Design and Asymmetric Synthesis of Potent and Neurotrophic Ligands for FK506‐Binding Proteins (FKBPs),"To create highly efficient inhibitors for FK506-binding proteins, a new asymmetric synthesis for pro-(S)-C(5) -branched [4.3.1] aza-amide bicycles was developed. The key step of the synthesis is an HF-driven N-acyliminium cyclization. Functionalization of the C(5) moiety resulted in novel protein contacts with the psychiatric risk factor FKBP51, which led to a more than 280-fold enhancement in affinity. The most potent ligands facilitated the differentiation of N2a neuroblastoma cells with low nanomolar potency.",10.1002/anie.201408776,2014-11-20,0.6194308847304173
Organic Letters,Total Synthesis of Natural <i>p</i>-Quinol Cochinchinenone,"Cochinchinenone has been synthesized in only five steps and four pots and in 58% overall yield from commercially available 2,3-dimethoxy-4-hydroxy-benzaldehyde and OPMB-protected p-hydroxy acetophenone, the key step being the oxone-mediated oxidative dearomatization of the corresponding ketone-containing p-substituted phenol.",10.1021/ol302858r,2012-11-20,0.6194181049488048
European Journal of Organic Chemistry,"Gram‐Scale Synthesis of Tomatidine, a Steroid Alkaloid with Antibiotic Properties Against Persistent Forms of <i>Staphylococcus aureus</i>","We herein describe the first diastereoselective synthesis of the Solanum alkaloid tomatidine 1 . The synthesis has been accomplished in 11 steps and 24.9 % overall yield (longest linear sequence). This methodology, which involves a convergent synthon insertion followed by a sequence of ring opening/nitrogen substitution/ring closing, allowed the generation of 1 on &gt; 2 g scale. The synthetic challenge with the diastereoselective generation of the unusual spiroaminoketal moiety was solved through a combined azide reduction/addition sequence. The first diastereoselective synthesis of the phytosteroid yamogenin is also reported. Tomatidine has shown promising antibiotic properties against persistent forms of Staphylococcus aureus ( S. aureus ) and methicillin‐resistant S. aureus (MRSA). In particular, it possesses the unique ability to kill persistent forms of S. aureus and MRSA while simultaneously potentiating the antibiotic efficacy of aminoglycoside antibiotics against wild type strains of the bacteria.",10.1002/ejoc.202000051,2020-04-03,0.6193933678932818
Tetrahedron,"A diastereoselective synthesis of 4(RS), 6(SR)-mercaptomethylmevalonolactone, a key intermediate in the preparation of a new class of inhibitors of HMG-CoA reductase",,10.1016/s0040-4039(00)94530-1,1983-01-01,0.619387679500352
European Journal of Organic Chemistry,"2‐(Benzylsulfanyl)‐6‐chloro‐9‐isopropylpurine, a Valuable Intermediate in the Synthesis of Diaminopurine Cyclin Dependent Kinase Inhibitors","Abstract The synthetic potential of a novel precursor of 2,6‐diaminopurine CDK inhibitors, 2‐(benzylsulfanyl)‐6‐chloro‐9‐isopropylpurine, is described. The Traube purine synthesis was chosen to prepare the required 2‐(benzylsulfanyl)hypoxanthine intermediate. Attempts to prepare its purin‐6‐yl methanesulfonic ester analogue failed. Conversion to the 6‐chloropurine derivative enabled the introduction of arylamines in the presence of catalytic amounts of acid. Further chemical variety was introduced on the purine through a regioselective Mitsunobu N ‐9 alkylation. Oxidative cleavage of the 2‐(benzylsulfanyl) leaving group with an aliphatic amine was implemented as previously reported. Purvalanol A, a potent CDK inhibitor, was synthesised using this methodology. The template and intermediates were fully characterised by modern spectroscopic techniques and single‐crystal X‐ray diffraction. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2005)",10.1002/ejoc.200400748,2005-03-01,0.6193847042977357
Tetrahedron,"Efficient synthesis of cytotoxic pyrido[1,2-e]purines from purines employing direct C-allylation and RCM–oxidation as key steps",,10.1016/j.tetlet.2013.04.084,2013-04-27,0.619375676568297
Tetrahedron,A concise route to tiazofurin,,10.1016/s0040-4039(02)01470-3,2002-09-01,0.6193656964107203
Tetrahedron,A concise route to isocanthin-6-one,,10.1016/s0040-4039(97)10794-8,1998-03-01,0.6193656964107203
Tetrahedron,A concise route to phytosphingosine from lyxose,,10.1016/s0040-4039(03)01281-4,2003-06-30,0.6193656964107203
Tetrahedron,A concise route to the right wing of ciguatoxin,,10.1016/s0040-4039(03)01214-0,2003-06-30,0.6193656964107203
Tetrahedron,A concise route to the C2-symmetric tricyclic skeleton of ryanodine,,10.1016/j.tetlet.2008.12.054,2008-12-25,0.6193656964107203
Organic Process Research & Development,Process Research of (<i>R</i>)-Cyclohexyl Lactic Acid and Related Building Blocks:  A Comparative Study,"( S )-Cyclohexyl lactic acid is a component of the selective E-selectin inhibitor 2 (( S )-cHexLact-2- O -(3-Galβ(1→3)ddGlc(4→1)αFuc). We describe the evaluation of various synthetic routes to this building block: ( A ) diazotation of phenylalanine followed by phenyl ring hydrogenation; ( B ) phenyl ring hydrogenation of phenyl alanine followed by diazotation; ( C ) acidic hydrolysis of the cyanohydrin derived from phenylacetaldehyde, enantiomeric resolution of the resulting, racemic phenyl lactic acid via diasteromeric salt formation and phenyl ring hydrogenation; ( D ) enantioselective dihydroxylation of a cinnamate ester, followed by hydrogenation of the benzylic hydroxy group and the aromatic nucleus; ( E ) enantioselective biocatalytic reduction of phenylpyruvic acid, followed by phenyl ring hydrogenation. The development of (2 R )-2- O -(4-nitrophenyl)sulfonyl-cyclohexyl lactic acid p -bromobenzylester 21 as a buidling block with improved crystallinity and stability is also described.",10.1021/op030202q,2003-06-27,0.6193626601160157
Organic Process Research & Development,Direct Synthesis of a PDE4 Inhibitor by Using Pd–Cu-Catalyzed C–H/C–Br Coupling of Benzoxazole with a Heteroaryl Bromide,"A short and practical synthetic route of a PDE4 inhibitor ( 1 ) was established by using Pd–Cu-catalyzed C–H/C–Br coupling of benzoxazole with a heteroaryl bromide. The combination of Pd(OAc) 2 -Cu(OTf) 2 -PPh 3 was found to be effective for this key step. Furthermore, telescoping methods were adopted to improve the yield and manufacturing time, and a two-step synthesis of 1 was accomplished in 71% overall yield.",10.1021/acs.oprd.6b00106,2016-05-10,0.619340438275368
European Journal of Organic Chemistry,Towards the Total Synthesis of Mycaperoxide B: Probing Biosynthetic Rationale,"Abstract Studies towards the biomimetic synthesis of mycaperoxide B ( 1 ) are described. We have established the synthesis of four diastereoisomers of mycaperoxide B methyl ester ( 1a ) by employing a Michael addition across an α,β‐unsaturated ester precursor 2 as the key step. This result strongly suggestsstereocontrol in the addition of the hydroperoxide functionality to the E double bond and discloses the importance of choosing the correct geometry of the α,β‐unsaturated double bond when attempting to synthesise mycaperoxide B. Four diastereoisomeric tetrahydrofurans derived from an intramolecular rearrangement of the 1,2‐dioxolane enolate 12 were also isolated and characterised.",10.1002/ejoc.201101477,2011-12-27,0.6193393280450089
Tetrahedron,"Synthesis and reactivity of the endo-tricyclo[4.2.0.02,8]oct-3-en-7-yl system; a δ route to the bicyclo[3.2.1]-octa-2,6-dien-8-yl cation",,10.1016/s0040-4039(01)91801-5,1974-01-01,0.6193343380792227
Journal of Organic Chemistry,Total Asymmetric Synthesis of the Potent Immunosuppressive Marine Natural Product Microcolin A,"The total asymmetric synthesis of the potent immunosuppressive compound microcolin A is reported. The synthesis establishes the absolute stereochemistry of microcolin A as C-36 R, C-38 R, and C-4 S on the basis of the diastereoselective preparation of all four possible diastereomers of the lipid region (fragment A) and diastereoselective synthesis of fragment C starting from natural l -( S )-alanine. The strategy involves a convergent assemblage of three optically pure fragments and is amenable to chemical modifications to examine structural analogs for biological study.",10.1021/jo952123l,1996-01-01,0.6193067502039487
Organic Process Research & Development,Flexible and Scalable Route to HDAc Inhibitors Containing an Unusual Trisubstituted Pyridine Core,"A scalable route to histone deacetylase inhibitors containing an unusual 2-aryl-3-cyano-5-aminomethylpyridine core has been developed which has the flexibility to deliver a range of compounds on at least a multigram scale. The key step involves a novel Mannich reaction using 3-dimethylaminoacrolein, formaldehyde, and a secondary amine to yield a 2-(alkylaminomethyl)-3-dimethylaminoacrolein. Tuning of this reaction in process development was fundamental to the success of the approach in terms of flexibility and operability on scale-up. This new methodology will also enable access an underutilised family of 3,5-disubstituted pyrid-2-ones and 2,3,5-trisubstituted pyridines.",10.1021/op300021m,2012-06-13,0.6192930856932037
Angewandte Chemie International Edition,The Catalytic Enantioselective Total Synthesis of (+)‐Liphagal,Ring a ding: The meroterpenoid natural product (+)-liphagal has been synthesized enantioselectively in 19 steps from commercially available materials. The trans-homodecalin system was achieved by ring expansion followed by stereoselective hydrogenation.,10.1002/anie.201101842,2011-06-10,0.6192869674777655
Tetrahedron,Total synthesis of the novel benzophenone NP-011694,,10.1016/j.tetlet.2015.06.075,2015-07-02,0.6192779179177117
Tetrahedron,Total synthesis of baiyunoside by a novel 2′ discriminated glycosidation,,10.1016/s0040-4039(00)96495-5,1987-01-01,0.6192779179177117
Tetrahedron,Total synthesis of the novel seco-prezizaane sesquiterpenoid (+)-1S-minwanenone,,10.1016/j.tetlet.2007.09.139,2007-10-24,0.6192779179177117
Tetrahedron,"Total synthesis of (±)-cycloseychellene, a novel tetracyclic sesquiterpene",,10.1016/s0040-4039(00)81570-1,1983-01-01,0.6192779179177117
Tetrahedron,The first total synthesis of the novel β-carboline alkaloid oxopropaline G,,10.1016/s0040-4039(98)00149-x,1998-04-01,0.6192779179177117
Tetrahedron,"Total synthesis of (−)-mniopetal E, a novel biologically intriguing drimane sesquiterpenoid",,10.1016/s0040-4039(99)01631-7,1999-10-01,0.6192779179177117
Tetrahedron,"Total synthesis of dl-asparenomycins A, B and C, novel carbapenem antibiotics",,10.1016/s0040-4039(01)80220-3,1984-01-01,0.6192779179177117
Tetrahedron,A novel expeditious entry into gibberellins. The total synthesis of (±)-GA5,,10.1016/s0040-4039(00)84359-2,1986-01-01,0.6192779179177117
Tetrahedron,"Total synthesis of (−)-dysiherbaine, a novel neuroexcitotoxic amino acid",,10.1016/s0040-4039(00)00518-9,2000-05-01,0.6192649174400379
Journal of Organic Chemistry,An Efficient Enantioselective Synthesis of (+)-Disparlure,"Synthesis of (+)-disparlure, 1, the sex pheromone of gypsy moth (Lymantria dispar), commenced from cis-vinyl epoxide 4 which was prepared by our asymmetric chloroallylboration in 99% de and 94% ee. Hydroboration of 4 using dicyclohexylborane in THF, followed by sodium perborate oxidation gave a crystalline cis-3,4-epoxy alcohol 3 whose enantiomeric purity was enhanced by recrystallization. Conversion of 3 to (+)-disparlure was via alkylation of the tosylate. (+)-Disparlure was produced in four steps with an overall yield of 27% and >/=99.5% ee.",10.1021/jo9820871,1999-04-28,0.6192621408994342
Tetrahedron,"Enantiospecific synthesis of (−)-3-iso-19,20-dehydro-β-yohimbine from secologanin: a route to normal and pseudo stereoisomers of yohimbine",,10.1016/s0040-4039(00)00912-6,2000-07-01,0.6192513221639954
Journal of Organic Chemistry,Total Synthesis of Iheyamine A via the Cyanide-Catalyzed Imino-Stetter Reaction,"The total synthesis of iheyamine A from readily available ethyl 2-aminocinnamate and 5-methoxyindole-2-carboxaldehyde is described. The cyanide-catalyzed imino-Stetter reaction of an aldimine derived from ethyl 2-aminocinnamate and 5-methoxyindole-2-carboxaldehyde provided the desired unsymmetrical 2,2'-bisindole-3-acetic acid derivative. The subsequent introduction of an amino group at the C-3' position, followed by the formation of the azepine ring, completed the total synthesis of iheyamine A.",10.1021/acs.joc.0c01051,2020-05-22,0.6192508031086077
Organic Letters,A New Convergent Route to Conduritols A−F from a Common Chiral Building Block,A diastereocontrolled route to conduritols A-F has been developed starting from a common chiral building block containing an oxabicyclo[3.2.1]octane framework.,10.1021/ol015963x,2001-05-01,0.619246979997525
Journal of Organic Chemistry,Discovery and Bioinspired Synthesis of Salpratone A,"Salpratone A ( 1 ), a novel abietane diterpenoid containing a unique cis -fused A/B ring, was isolated from Salvia prattii . Bioactivity studies showed that 1 has potent activity in inhibiting platelet aggregation induced by multiple agonists as well as antithrombotic efficacy in the FeCl 3 -induced rat in vivo thrombosis model. Furthermore, a bioinspired synthesis of 1 from the abundant natural product ferruginol was achieved in 6 steps with a 22% overall yield. The key steps include a stereoselective allyl oxidation and a subsequent regioselective Meinwald rearrangement.",10.1021/acs.joc.3c02584,2024-01-12,0.6192463881329252
Angewandte Chemie International Edition,Concise and Efficient Total Synthesis of <i>Lycopodium</i> Alkaloid Magellanine,The power of the masked o-benzoquinone Diels–Alder protocol is shown in a total synthesis of magellanine ((±)-3). The highly compact molecular architecture of 3 was constructed from acetovanillone (1) via a masked o-benzoquinone 2 in an overall yield of 12 % over 16 steps (or 9 % over 14 steps).,10.1002/1521-3773(20021104)41:21<4090::aid-anie4090>3.0.co;2-#,2002-10-31,0.6192438876413922
Journal of the American Chemical Society,Asymmetric Synthesis of Pyrrolidinoindolines. Application for the Practical Total Synthesis of (−)-Phenserine,"A versatile route to enantiopure 3,3-disubstituted oxindoles and 3a-substituted pyrrolidinoindolines is described in which diastereoselective dialkylation of enantiopure ditriflate 10 with oxindole enolates is the central step. These reactions are rare examples of alkylations of prostereogenic enolates with chiral sp(3) electrophiles that proceed with high facial selectivity (10-20:1). The scope of this method is explored, and a model to rationalize the sense of stereoselection is advanced. This dialkylation chemistry was used to synthesize (-)-phenserine on a multigram scale in six steps and 43% overall yield from 5-methoxy-1,3-dimethyloxindole (27) and to complete a short formal total synthesis of (-)-physostigmine (2).",10.1021/ja046690e,2004-10-12,0.6192406910607837
Organic Letters,Progress toward the Total Synthesis of Frondosin C,"A straightforward approach toward the total synthesis of frondosin C is described. This strategy involves a key one-pot, microwave-assisted 5-exo cyclization-Claisen rearrangement sequence that was used for the expedient assembly of the frondosic C scaffold. Subsequent manipulation of the tetracyclic core allowed the synthesis of an advanced intermediate bearing the characteristic diene moiety in the B ring. [reaction: see text]",10.1021/ol0620848,2006-09-27,0.6192402207054464
Tetrahedron,"The synthesis of thrombin inhibitor L-370,518 via an α-hydroxy-β-lactam",,10.1016/0040-4039(96)01013-1,1996-07-01,0.6192316447893633
Synthesis,"Expedient Synthesis of 4(5)-[1-(2,3-Dimethylphenyl)ethyl]-1<i>H</i>-imidazole, the α<sub>2</sub>-Adrenergic Agonist Medetomidine","All articles of this category (±)-4(5)-[1-(2,3-Dimethylphenyl)ethyl]-1 H -imidazole hydrochloride ( 5 ) is prepared in three steps in 79% overall yield from 1-( N,N -dimethylsulfamoyl) imidazole by bis-protection, regioselective lithiation followed by an efficient tandem addition-reduction of the resulting 2,3-dimethylbenzoyl chloride adduct with lithium/ammonia/ammonium chloride.",10.1055/s-1991-26637,1991-01-01,0.6192300249120023
European Journal of Organic Chemistry,"Pyrazolyldiazonium Salts in the Synthesis of 4‐Amino‐1,3’‐bipyrazoles","Abstract An efficient protocol for the synthesis of fluorescent 4‐amino‐1,3′‐bipyrazoles, which are substituted at the positions N‐1′, C‐4′, C‐3 and C‐5, is described. By a two‐step synthetic strategy, an initial azo coupling of ethyl cyanoacetate and various 1‐alkylpyrazolyldiazonium chlorides gave substituted ethyl 2‐cyano‐2‐(2‐(pyrazol‐3‐yl)hydrazine‐ylidene)acetates, which were subsequently subjected to Thorpe‐Ziegler type cyclisation reactions to yield the title compounds.",10.1002/ejoc.202301049,2023-12-07,0.6192298432517626
European Journal of Organic Chemistry,Regio- and Stereoselective Opening of Oxiranes through Neighbouring Group Participation: Stereocontrolled Synthesis of Enantiopure Hydroxylated Oxazolidin-2-ones,"The regio- and stereo-selective ring opening of (S)-pyroglutaminol derived epoxides provides an effective route to protected syn,syn-aminodiol units. The procedure involves the chemoselective aminolysis or alcoholysis of (3R,4R,5R)-N-(tert-butoxycarbonyl)-3,4-epoxy-5-[(1-ethoxy)ethoxymethyl]pyrrolidin-2-one (10), followed by the formation in quantitative yield of oxazolidinone intermediates, through the mediation of neighbouring N-Boc groups. The practical synthetic interest of this route is illustrated by the example of (3R,4S,5R)-3,4-diacetoxy-5-(acetoxymethyl)pyrrolidin-2-one which should serve as useful building block in further syntheses.",10.1002/(sici)1099-0690(199912)1999:12<3483::aid-ejoc3483>3.0.co;2-e,1999-12-01,0.6192284269922325
Journal of Organic Chemistry,"Synthesis of stenusine, the spreading agent of the beetle Stenus comma","Stenusine [1-ethyl-3-(2-methylbutyl)piperidine], the spreading agent of Stenus comma, was synthesized by a six-step sequence in 21 % overall yield from acetaldehyde. Acetaldehyde was converted into the corresponding N-tert-butyl aldimine, which was sequentially alkylated via its 1-azaallylic anion with 1-bromo-2-methylbutane and 1-bromo-3-chloropropane. The resulting delta-chloro aldimine was hydrolyzed into the delta-chloro aldehyde, which was converted into the corresponding N-ethyl aldimine. The latter labile delta-chloro aldimine was cyclized with lithium aluminum hydride to afford stenusine. The 1-tert-butyl analogue of stenusine was synthesized using an analogous route.",10.1021/jo00053a025,1993-01-01,0.6192020918524922
Organic Letters,Development of a Novel Pd-Catalyzed <i>N</i>-Acyl Vinylogous Carbamate Synthesis for the Key Intermediate of ICE Inhibitor VX-765,"A novel Pd-catalyzed coupling of Cbz-protected proline amide with 4-bromo-5-ethoxyfuran-2(5H)-one was developed for the synthesis of the P1-P2 unit (5) of VX-765. The process afforded quantitative coupling in the presence of water, providing a 1:1 mixture of 5 and its ethoxy epimer epi-5. Compound 5 was isolated as a single diastereomer via fractional crystallization, which was stereoselectively converted to 17 via hydrogenation, and subsequently transformed to VX-765. Nine examples of the Pd coupling are presented with yields ranging from 76-98%.",10.1021/ol702532h,2007-12-15,0.6192019216212936
Synthesis,"Enantioselective Synthesis of (<i>S</i>)-3-Hydroxy-3-phenyl-3,4-dihydroquinolin-2(1<i>H</i>)-one Ring System","A series of new enantiomerically pure (S)-3-hydroxy-3-phenyl-3,4-dihydroquinolin-2(1H)-ones was prepared in good yields according to a two-step synthesis using a benzylation of the sodium enolate of the (2S,5S)-cis-2-tert-butyl-5-phenyl-1,3-dioxolan-4-one with substituted o-nitrobenzyl bromides followed by reduction of the nitro group to amine with concomitant intramolecular aminolysis of the dioxolanone ring.",10.1055/s-2006-958928,2006-12-20,0.6191963694240699
Journal of Organic Chemistry,Total Synthesis of the Four Enantiomerically Pure Diasteroisomers of the Phytoprostanes E<sub>1</sub>Type II and of the 15-E<sub>2t</sub>-Isoprostanes,"Syntheses of the four enantiomerically pure diastereoisomers of the phytoprostanes E1 type II and 15-E2t-isoprostanes (1-4) are described. The key steps included the preparation of the Freïmanis (+/-)-hydroxycyclopentenone 5, enzymatic resolution of this racemic hydroxycyclopentenone, Wittig and Horner-Wadsworth-Emmons (HWE) coupling reactions and finally enantioselective reductions.",10.1021/jo702455g,2008-03-20,0.6191926205871272
Synlett,"A Concise Organocatalytic Route to Protected (2S,4R)-4-Hydroxyornithine and (+)-Pseudohygroline","A practical, efficient, and organocatalytic approach to the synthesis of (2 S ,4 R )-4-hydroxyornithine and (+)-pseudohygroline is reported using proline-catalyzed sequential α-aminoxylation/α-amination reaction and Horner–Wadsworth–Emmons olefination reaction of an aldehyde as the key step.",10.1055/s-0033-1340977,2014-03-14,0.6191847453436187
Tetrahedron,()-pyroglutamic acid as a chiral starting material for asymmetric synthesis,,10.1016/s0040-4039(00)79672-9,1991-03-01,0.6191767672644141
European Journal of Organic Chemistry,Synthesis of Bicyclic and Tricyclic Chiral Guanidinium Salts by an Intramolecular Alkylation Approach,"Synthetic studies leading to three new types of chiral guanidinium scaffolds are described. Structures of interest include bicyclic guanidine derivatives with various substitution patterns around the guanidine core, as well as a highly rigid tricyclic scaffold. The challenging targets were accessed by application of mercury(II)‐promoted guanylation of N ‐Boc‐substituted thioureas and Ishikawa's desulfurative cyclization. In addition to our synthetic logics, a scalable synthesis of the tricyclic guanidinium salt is presented.",10.1002/ejoc.201601154,2016-10-17,0.6191739572394092
Tetrahedron,"Reactions of 1,2-diorganoboranes with airline silver nitrate - a new route to olefins",,10.1016/s0040-4039(00)78934-9,1976-12-01,0.6191679231992763
Synthesis,"Efficient Synthesis of Iminoctadine, a Potent Antifungal Agent and Polyamine Oxidase Inhibitor (PAO)","Iminoctadine (1,17-diguanidino-9-azaheptadecane), isolated from a mixture of polyamines and guanidines known as guazatine that is used in agriculture as a fungicide, showed interesting activity as human antifungal agent and PAO inhibitor. In this paper, we propose a straightforward synthetic strategy for obtaining pure iminoctadine tris(trifluoroacetate) in high overall yield. © Georg Thieme Verlag Stuttgart.",10.1055/s-2007-983898,2007-09-24,0.6191625654269186
Tetrahedron,A simple one-pot procedure for the iminium salt formation: an efficient route to β-arylethylamines,,10.1016/j.tetlet.2005.01.027,2005-01-26,0.619154662947946
Journal of Organic Chemistry,Asymmetric Synthesis of Calyculin C. 1. Synthesis of the C<sub>1</sub>−C<sub>25</sub> Fragment,"We report our synthesis of the C(1)-C(25) fragment of serine/threonine phosphatase PP1 and PP2A inhibitor, calyculin C. Synthetic efforts were directed initially toward the synthesis of a spiroketal core fragment (7), which culminated in completion of the bottom half of the natural product. The synthesis of fragment 7 and subsequent elaboration relied on an allylboration strategy for introduction of chirality. The C(1)-C(8) fragment representing the potentially unstable tetraene moiety was introduced as a separate entity.",10.1021/jo960314y,1996-01-01,0.6191375381436018
Journal of Organic Chemistry,A → J Prostaglandin Swap:  A New Tactic for Cyclopentenone Prostaglandin Synthesis,"A practical methodology for the synthesis of J-type prostaglandins has been developed starting from the well-consolidated approaches established for the synthesis of A-type prostaglandins. An efficient 1,3-allylic transposition of the C-9 hydroxyl group of intermediate 4 furnished the advanced precursor 5 for J(2) synthesis. Our optimized A-J swap protocol employed selenium chemistry, involving the [2,3] sigmatropic rearrangement of secondary allylic selenoxide 11a.",10.1021/jo034501p,2003-07-19,0.6191298655456354
Synlett,An Ytterbium-Catalysed Intramolecular Aldehyde-Ene Reaction Approach to the Guaianolide and Pseudoguaianolide Diterpenoids: Synthesis of the Guaiane Skeleton,"A convergent approach to a functionalised guaiane ring system, the core of the guaianolide and pseudoguaianolide diterpenes, is described. The synthesis utilises an intramolecular aldehydeene reaction as the key step.",10.1055/s-2006-956461,2006-12-01,0.6191124313751855
Tetrahedron,An alternative route to 4-benzoyl-2-azetidinones,,10.1016/s0040-4039(00)78822-8,1980-01-01,0.6191100423373709
Angewandte Chemie International Edition,Total Synthesis of Calophyline A,"Reported herein is the total synthesis of calophyline A, an indoline natural product possessing distinct ring connectivity which has not been synthesized previously. The synthetic route features several key transformations, including an aza-pinacol rearrangement to construct the nitrogen-containing bridged [3.2.2] bicycle, a Heck cyclization to assemble the fused 6/5/6/5 ring system, and a challenging late-stage aldol reaction to generate both a neopentyl quaternary stereogenic center and an oxygen-containing bridged [3.2.1] bicycle.",10.1002/anie.201604770,2016-06-13,0.6191012583014084
Synlett,A Stereoselective Synthesis of the C13-C19 Fragment of Sanglifehrin A,"All articles of this category A short, stereoselective route to the C13-C19 fragment of the immunosuppressant sanglifehrin A 1 , is presented. The key step involves a highly diastereoselective boron aldol reaction between β-ketoimide 11 and triisopropylsilyl propargyl aldehyde 21c . sanglifehrin A - β-ketoimide - methyl ester - tellurium",10.1055/s-2000-6518,2000-01-01,0.6190888211766266
Journal of Organic Chemistry,"Gram-Scale Laboratory Synthesis of UM171, a Potent Agonist of Human Hematopoietic Stem Cell Self-Renewal","A short economic synthesis of pyrimidoindole derivative UM171, a potent agonist for the ex vivo expansion of hematopoietic stem cells, has been developed in this work. A unique [3,3]-sigmatropic rearrangement upon a hydroxamic precursor followed by base-promoted cyclization was successfully applied as the key step, furnishing the fully functionalized indole nucleus. The current synthesis is not only capable of affording UM171 in gram quantities but also offers great flexibility in late-stage diversification. Three new analogues of UM171 were synthesized accordingly in excellent yields using the common indole-carboxamide intermediate.",10.1021/acs.joc.6b01094,2016-06-23,0.6190656518243671
Tetrahedron,A short synthesis of a key leukotriene B4 synthon,,10.1016/s0040-4039(00)81421-5,1983-01-01,0.6190609864674793
Journal of the American Chemical Society,Total Synthesis and Anti-Cancer Activity of All Known Communesin Alkaloids and Related Derivatives,"High Resolution Image Download MS PowerPoint Slide A unified enantioselective total synthesis and anticancer evaluation of all known epoxide-containing communesin alkaloids and related derivatives is described. Our synthesis is predicated on the convergent and modular diazene-directed assembly of two complex fragments to secure the critical C3a–C3a′ linkage followed by a guided biomimetic aminal reorganization to deliver the heptacyclic core of these alkaloids. Concise enantioselective syntheses of the fragments were devised, with highlights including the application of a rationally designed sulfinamide chiral auxiliary, an efficient calcium trifluoromethanesulfonate promoted intramolecular amination, and a diastereoselective epoxidation that simultaneously converts the new chiral auxiliary to a versatile amine protective group. The modularity of our convergent approach enabled the rapid synthesis of all epoxide-containing members of the communesin family from a single heterodimeric intermediate, including the first total synthesis of communesins C–E, and G–I, and facilitated our stereochemical revision of (−)-communesin I, the most recently isolated communesin alkaloid. Furthermore, the generality of our biogenetically inspired heterodimer rearrangement was demonstrated in a guided synthesis of a communesin derivative with an unnatural topology. Finally, we report the first comparative analysis of the anticancer activities of all naturally occurring communesin alkaloids A–I and eight complex derivatives against five human cancer cell lines. From these data, we have identified (−)-communesin B as the most potent natural communesin and discovered that derivatives with N 8′-sulfonamide substitution exhibit up to a 10-fold increase in potency over the natural alkaloids.",10.1021/jacs.9b07397,2019-08-17,0.6190589820088995
Journal of Organic Chemistry,De Novo Syntheses of Coumaronochromones: Application in Total Synthesis of Cristatone II,"synthetic route for coumaronochromones is reported. The route featured a Buchwald-Hartwig-Miura (BHM) arylation and DDQ-mediated oxidative cyclization cascade. A diverse library of 20 coumaronochromones bearing various substitution patterns was constructed. Moreover, the practical utility of this method was unequivocally demonstrated by a seven-step total synthesis of natural product cristatone II in an 18% overall yield from commercially available phenols. This approach provides a valuable tool for the facile preparation of coumaronochromone-based bioactive natural products and their derivatives.",10.1021/acs.joc.5c00817,2025-05-29,0.6190570231701106
Journal of Organic Chemistry,Diversity-Oriented Approach Toward the Syntheses of <i>Amaryllidaceae</i> Alkaloids via a Common Chiral Synthon,"Functionalized hydroindole (1), a common chiral synthon, for versatile transformations to synthesize a broad range of Amaryllidaceae alkaloids (AAs) including (-)-crinine, (-)-crinane, (-)-amabiline, (+)-mesembrine, (-)-maritidine, (-)-oxomaritidine, and (+)-mesembrane is reported. Scaffold 1 is found as a prime structural motif in a wide variety of the AAs and is a novel synthon toward designing a divergent route for the synthesis of these natural products. This is established in a few steps, starting from a chiral aza-bicyclo-heptene sulfone scaffold (2) via conjugate addition and concomitant stereoselective ring opening with allylmagnesium bromide, a key step that generates a crucial quaternary stereocenter, fixing the stereochemistry of the rest of the molecule at an early stage. One carbon truncation followed by intramolecular reductive amination led to the desired core 1 in a multigram scale.",10.1021/acs.joc.8b01368,2018-07-13,0.6190433490433044
Angewandte Chemie International Edition,"A New Efficient Synthesis of (R,R)-2,2′-Bipyrrolidine: An Interesting Chiral 1,2-Diamine withC2 Symmetry","Making stairs: A new conformational concept is presented for the synthesis of derivatives of C2-symmetrical 1,2-diamines, where a stairlike arrangement is imposed on the molecule. A new efficient synthesis of (R,R)-bipyrrolidine is described; the picture shows the X-ray structure of the (R,R)-bipyrrolidine/ZnCl2 complex.",10.1002/1521-3773(20001117)39:22<4093::aid-anie4093>3.0.co;2-r,2000-11-17,0.6190426107362083
Organic Letters,"First Asymmetric Total Syntheses of Cernuane-Type Lycopodium Alkaloids, Cernuine, and Cermizine D","The first total syntheses of two cernuane-type Lycopodium alkaloids, (-)-cernuine and (+)-cermizine D, were accomplished starting from (+)-citronellal. The syntheses involved organocatalytic alpha-amination to afford oxazolidinone, which is used for diastereoselective allylation, and asymmetric transfer aminoallylation followed by stereoselective construction of an aminal moiety as key steps.",10.1021/ol800574v,2008-04-23,0.6190388028543299
Journal of Organic Chemistry,Chemical Modification of a Highly Functionalized Taxane. The Consequences of an Absent Bridgehead Double Bond on Oxetane D-Ring Construction,"An oxetane D-ring has been fused to the framework of the highly functionalized taxane 2. The synthetic route is based on a trimethylsilyl triflate-promoted epoxide-opening step, followed by stereocontrolled, regioreversed oxirane formation and reductive transposition of this intermediate with bis(cyclopentadienyl)titanium(III) chloride. This last key step provides for the convenient implementation of additional hydroxyl groups ultimately conducive to intramolecular S(N)2 reaction. Tangential features of the route outlined herein include specific rearrangement reactions and a retro-aldol cleavage of ring A.",10.1021/jo0206566,2003-02-19,0.6190298773243817
Organic Letters,Synthesis of Carboxy ATTO 647N Using Redox Cycling for Xanthone Access,"A synthesis of the carbopyronine dye Carboxy ATTO 647N from simple materials is reported. This route proceeds in 11 forward steps from 3-bromoaniline with the key xanthone intermediate formed using a new oxidation methodology. The step utilizes an oxidation cycle with base, water, iodine, and more than doubles the yield of the standard permanganate oxidation methodology, accessing gram-scale quantities of this late-stage product. From this, Carboxy ATTO 647N was prepared in only four additional steps. This facile route to a complex fluorophore is expected to enable further studies in fluorescence imaging.",10.1021/acs.orglett.9b03981,2019-12-11,0.6190263671214181
Tetrahedron,"2,5-S,S-Dicysteinyldopa: A new amino acid in the eye of the gar and its enzymic synthesis",,10.1016/s0040-4039(00)91427-8,1975-01-01,0.6190211916316255
Tetrahedron,Synthesis of bulgecinine: a new amino acid in bulgecins,,10.1016/s0040-4039(00)94943-8,1985-01-01,0.6190211916316255
Tetrahedron,A new route to isoindole (benzo[c]indole) and its derivatives.,,10.1016/s0040-4039(01)94299-6,1972-01-01,0.6190165823973792
Journal of Organic Chemistry,Enantiocontrolled Synthesis of (+)-Boronolide,"(+)-Boronolide 1, a δ-lactonic polyacetoxy natural product isolated from the bark and branches of Tetradenia fruticosa and from the leaves of Tetradenia barberae, has been stereoselectively synthesized, the key steps being the chemoselective Sharpless asymmetric dihydroxylation of ( E )-1-( tert -butyldimethylsiloxy)-7-dodecen-5-yne ( 6 ), Lindlar reduction of the triple bond of diacetate 9, and further diastereoselective dihydroxylation of the resulting cis -olefin 5 .",10.1021/jo960267+,1996-01-01,0.6190137484257896
Journal of Organic Chemistry,Formal Total Synthesis of (+)-Salicylihalamides A and B:  A Combined Chiral Pool and RCM Strategy,"The formal total synthesis of the (+)-salicylihalamides A and B is detailed, utilizing a chiral pool approach to generate the three stereogenic centers and a ring-closing metathesis (RCM) for the formation of the macrocyclic ring structure. Starting from a known glucose-derived alcohol, the formal total synthesis was achieved in an efficient 13-step protocol in 26% overall yield. It was found that substitution at the remote phenolic group significantly influenced the ratio of the E- and Z-double bond products in the RCM step. The introduction of phenol protecting groups provided E-isomers preferentially and also enhanced the rates of the RCM reactions.",10.1021/jo0301550,2003-11-21,0.6190061135298468
Synthesis,A Novel and Enantioselective Total Synthesis of (20S)-Camptothecin via a Sharpless Asymmetric Dihydroxylation Strategy,All articles of this category (opens in new window),10.1055/s-0031-1289575,2011-10-25,0.6189963575178808
Tetrahedron,New route to 15-hydroxydehydroabietic acid derivatives: application to the first synthesis of some bioactive abietane and nor-abietane type terpenoids,,10.1016/j.tetlet.2006.02.037,2006-03-01,0.6189880516108993
Synthesis,A Novel Route to Iridoids: Enantioselective Syntheses of Isoiridomyrmecin and α-Skytanthine,"Enantio- and diastereoselective syntheses of the iridoids (-)-isoiridomyrmecin and (+)-α-skytanthine from a common intermediate (6-bromo-3,3a,6,6a-tetrahydro-2H-cyclopenta[b]furan-2-one) were achieved. Key steps in both syntheses are conjugated nucleophilic substitutions (SN2′ anti-reactions) with C1 zinc cyanocuprates.",10.1055/s-2002-34382,2002-09-26,0.618981301439887
European Journal of Organic Chemistry,"Expeditious Route Towards (±)‐Desethyleburnamonine, a Precursor of (±)‐Vindeburnol","Abstract An expeditious route to (±)‐desethyleburnamonine ( 1 ), a direct precursor of vindeburnol, is reported. Microwave irradiation of an indolo‐tetrahydropyridine ethyl ester 2 in CH 3 CN in the presence of 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) gave the pentacyclic (±)‐desethyleburnamonine in a one‐pot process. Experimental evidence support an allylamine–enamine isomerization, followed by a rare Pictet–Spengler condensation in basic media. From commercially available 3‐(2‐bromo‐ethyl)indole and ethyl pyridin‐3‐yl acetate, (±)‐desethyleburnamonine was obtained in 52 % yield over three steps.",10.1002/ejoc.201101058,2011-10-10,0.6189808428206399
Organic Process Research & Development,Development of a Fit-for-Purpose Large-Scale Synthesis of an Oral PARP Inhibitor,"Compound ( 1 ) a poly(ADP-ribose)polymerase (PARP) inhibitor has been made by a fit-for-purpose large-scale synthesis using either a classical resolution or chiral chromatographic separation. The development and relative merits of each route are discussed, along with operational improvements and extensive safety evaluations of potentially hazardous reactions.",10.1021/op2000783,2011-05-18,0.6189807856449031
Journal of Organic Chemistry,Total Synthesis of (±)-Cylindricines A and B,"Cylindricine A (1) and cylindricine B (2) have been synthesized in 11 steps and 19% overall yield. The key reaction involves the addition of an organocopper species to a bicyclic vinylogous amide, which provides complete stereocontrol over the installation of the hexyl side chain.",10.1021/jo991020q,1999-10-01,0.6189711313156052
Tetrahedron,"Dithiocarbamate as an efficient intermediate for the synthesis of 2-amino-1,3,4-thiadiazoles in water",,10.1016/j.tetlet.2009.11.100,2009-11-28,0.6189687680242468
Journal of Organic Chemistry,Combined Directed Ortho Metalation/Cross-Coupling Strategies:  Synthesis of the Tetracyclic A/B/C/D Ring Core of the Antitumor Agent Camptothecin,"A convergent synthesis of the A/B/C/D ring fragment 5 of camptothecin using a combination of directed ortho metalation and Negishi cross-coupling is described. The key features of the synthetic sequence are an anionic ortho-Fries rearrangement (10 --> 12), a Negishi cross-coupling (7 --> 6), and a terminal modified von Braun reaction (16 --> 5) that leads to tetracyclic derivative 5 in 7 steps and 11% overall yield.",10.1021/jo049890h,2004-10-21,0.6189649584059868
Organic Process Research & Development,Practical Synthesis of a Peptide Deformylase (PDF) Inhibitor,"A practical chromatography-free synthesis of an N -formylated hydroxylamine peptide deformylase inhibitor LCD320 is described. A diastereoselective Michael reaction of (4 S )-3-[2-(cyclobutylmethyl)-1-oxo-2-propenyl]-4-(phenylmethyl)-2-oxazolidinone with O -benzyl hydroxylamine was used to establish the key stereogenic center. We found that traces of residual Li + from a previous step had a great impact on the diastereoselectivity of this reaction. A very efficient amidation coupling reaction of proline derivative (2 S,4 R )-4-fluoro-1,2-pyrrolidinedicarboxylic acid 1,1-dimethylethyl ester with weakly nucleophilic 3-pyridazinamine using methanesulfonyl chloride in the presence of 1-methylimidazole in DMF was also developed that proceeded without racemization.",10.1021/op700265n,2008-01-23,0.6189560595496394
Synthesis,Total Synthesis of Laingolide A Diastereomers,"The first total syntheses of two (±)-laingolide A diastereomers were achieved in 11 and 12 steps, respectively. The key steps include a tandem cross-dimerization/oxonia-Cope reaction and an intramolecular dehydrative cyclization for the formation of either the trans - or cis -enamide moieties.",10.1055/s-0034-1380133,2015-02-11,0.618955171273487
Tetrahedron,"(2R,3S,5S)-2-Acetoxy-3-fluoro-5-(p-toluoyloxymethyl)tetrahydrofuran: a key intermediate for the practical synthesis of 9-(2,3-dideoxy-2-fluoro-β-d-threo-pentofuranosyl)adenine (FddA)",,10.1016/s0040-4039(01)00855-3,2001-07-01,0.6189401262953135
European Journal of Organic Chemistry,Total Synthesis of (–)‐Isopisiferin: Confirmation of Absolute Configuration,"Abstract Starting from 4,4‐dimethyl‐2‐cyclohexenone, an enantioselective synthesis of (–)‐isopisiferin has been accomplished in 15 steps with an overall yield of 11.4 %. This work not only provides synthetic evidence for confirming the absolute configuration of natural isopisiferin itself, but also serves as an additional correlation origin to which many related icetexane‐type diterpenes, particular for the pisiferin family, can be referred.",10.1002/ejoc.201000449,2010-06-08,0.6189370757235749
Synthesis,"A New, Convenient Preparation of<i>cis</i>-(±)2-Acetyl-1-methylcyclobutaneacetic Acid, a Key Intermediate in the Synthesis of (±)Grandisol",,10.1055/s-1979-28880,1979-01-01,0.6189364438792312
Organic Letters,Total Synthesis of Lodopyridone,"A convergent total synthesis of the structurally unprecedented alkaloid lodopyridone was achieved using a cross-coupling of an iodopyridone fragment with a quinolinethiazolylstannane. Key features of the syntheses of the pentasubstituted 4-pyridone were a regioselective bromination of a 4-pyridone derived from kojic acid, a subsequent Cu-mediated introduction of the thioether, and a directed lithiation/iodination step. A chemoselective Negishi cross-coupling of a dibromothiazole and a quinolinylzinc reagent was used to assemble the chloroquinolinethiazol moiety.",10.1021/ol302121w,2012-08-21,0.618932370863374
Organic Letters,An Improved Synthesis of the “Miracle Nutrient” Coenzyme Q<sub>10</sub>,"[reaction: see text] A new route to the key coupling partner, chloromethylated CoQ0 (1), allows for direct formation of CoQ10 (3) via nickel-catalyzed cross-coupling with the side chain in the form of an in situ-derived vinyl alane (2).",10.1021/ol051329y,2005-08-18,0.6189166168266164
Organic Process Research & Development,Development of a Practical Synthesis of a Pyrazolopyridinone-Based p38 MAP Kinase Inhibitor,"A practical synthesis of the pyrazolopyridinone-based p38 MAP kinase inhibitor ( 4 ) was required for an ongoing program. The synthesis of a key pyrazolopyridinone building block was refined and optimized to provide kilogram quantities of 10 without chromatography or extractive workups. An efficient building-block strategy was employed to give optimal control of the key quality attributes, and in situ Raman spectroscopy was used to monitor and understand the complex solid-state properties of 4 .",10.1021/op100205s,2010-11-16,0.6189097924672531
Organic Letters,"Total Synthesis of A Novel Tetracyclic Alkaloid, Cassiarin F from the Flowers of <i>Cassia siamea</i>","A novel alkaloid, cassiarin F (1), which showed potent antiplasmodial activity against Plasmodium falciparum in vitro, was isolated from the flowers of Cassia siamea, and its structure was elucidated on the basis of 2D NMR analyses. A total synthesis of 1 was also achieved by employing the Suzuki coupling constructing biaryl unit, nucleophilic aromatic substitution, and Houben-Hoesch type ring construction as key steps.",10.1021/ol201674a,2011-07-14,0.6189092539536786
Angewandte Chemie International Edition,A Synthetic Route to Human Insulin Using Isoacyl Peptides,"The chemical synthesis of insulin has been a longstanding challenge, mainly because of the notorious hydrophobicity of the A chain and the complicated topology of this 51-mer peptide hormone consisting of two chains and three disulfide bonds. Reported herein is a new synthetic route utilizing the isoacyl peptide approach to address the hydrophobicity problems. The incorporation of isoacyl dipeptide segments into both A and B chains greatly improved their preparation and purification, and the RP-HPLC recovery of the chain ligation intermediates. The new route affords human insulin with a yield of 68 % based on the starting purified A chain and an overall yield of 24 % based on the substitution of the resin used for the preparation of A chain. To the best of our knowledge, this represents the most efficient route of human insulin chemical synthesis reported to date.",10.1002/anie.201310735,2014-03-11,0.6189051231148359
Synlett,An Alternative Synthetic Route to the C(11)-C(17)-Fragment of Mycinolide IV,"All articles of this category An efficient chiral synthesis of (4 R ,5 R )-4-(4-methoxybenzyloxymethyl)-2-heptene-1,5-diol ( 4 ), which corresponds to the C(11)-C(17) segment of mycinolide IV ( 1 ), is described. One of the key steps is the asymmetric pinacol-type rearrangement of a chiral glycerol-derived mesylate 12 , promoted by a modified organoaluminum reagent (1:1 mixture of trimethylaluminium and diethyl ether). Stereospecific 1,2-shift of a three-carbon alkenyl group gave ( R )-4-(4-methoxybenzyloxymethyl)-5-trimethylsilyl-7-(2-trimethylsilylethoxymethoxy)-5-hepten-3-one ( 13 ) 80 % yield. Reduction of 13 with lithium triethylborohydride followed by removal of silyl groups gave 4 in enantio- and diastereomerically pure form.",10.1055/s-1992-21289,1992-01-01,0.6188899149232323
Organic Process Research & Development,Route Selection and Optimization in the Synthesis of Two Imidazopyridine Inhibitors of DGAT-2,The scalable syntheses of two imidazopyridine inhibitors of the enzyme diacylglycerol acyltransferase 2 (DGAT-2) are described. 6-Chloro-3-nitro-2-aminopyridine was the starting material for the convergent synthesis of the central imidazopyridine ring. Differentiation in reactivity of the C2- and C3-nitrogen substituents on the pyridine ring and the development of mild cyclodehydration conditions to form the imidazole ring were critical problems that were addressed to deliver a 3-kg batch of compound 1 (PF-06424439) and a 0.1-kg batch of compound 2 (PF-06450561).,10.1021/acs.oprd.8b00005,2018-02-14,0.6188851087749687
Tetrahedron,"A new synthesis of nebularine and 7-D-ribofuranosylpurine (synthesis in nucleoside antibiotics, part I)",,10.1016/s0040-4039(01)99678-9,1966-01-01,0.6188772963665193
Journal of Organic Chemistry,Nucleophilic Aromatic Substitution of Methacrylamide Anion and Its Application to the Synthesis of the Anticancer Drug Bicalutamide,"The anticancer drug (R,S)-biscaltamide was prepared in three steps in >90% overall yield. A key step in the new synthesis involved a new nucleophilic aromatic substitution reaction of methacrylamide anion.",10.1021/jo035377c,2003-12-01,0.6188765780911202
Organic Letters,Total Synthesis of Dysifragilones A and B and Dysidavarone C,"The concise synthesis of dysifragilones A and B and dysidavarones has been accomplished for the first time in a divergent way from a common intermediate. The synthetic route features an intramolecular reductive Heck reaction to construct the 6/5/6/6/-tetracycle of dysifragilones A and B and an intramolecular palladium-catalyzed α-arylation of a sterically hindered ketone to forge the tetracyclo[7.7.1.0 2,7 .0 10,15 ]heptadecane core structure of dysidavarone C. The late-stage introduction of amino and ethoxy groups is effective.",10.1021/acs.orglett.1c02641,2021-08-30,0.6188568357414613
Synthesis,"Selective Nosylation of 1-Phenylpropane-1,3-diol and Perchloric Acid Mediated Friedel-Crafts Alkylation: Key Steps for the New and Straightforward Synthesis of Tolterodine","We have developed a new and straightforward synthesis of racemic tolterodine [N,N-diisopropyl-3-(2-hydroxy-5-methyl­phenyl)-3-phenylpropanamine]. The synthesis involves selective nosylation on the primary alcohol of 1-phenylpropane-1,3-diol using 4-nitrobenzenesulfonyl chloride, subsequent diisopropylamine substitution, and Friedel-Crafts alkylation using aqueous perchloric acid.",10.1055/s-2008-1067084,2008-05-16,0.6188474070322898
Journal of the American Chemical Society,Synthesis of Pluraflavin A “Aglycone”,"The ""aglycone"" of pluraflavin A (2) has been synthesized. The key features of this synthesis include a 1,3-dipolar cycloaddition between a nitrile oxide (cf. 14) and an olefin (22) to yield an isoxazoline followed by subsequent conversion into the gamma-pyrone of pluraflavin A. The epoxide moiety linked to the pyrone is installed prior to Diels-Alder installation of the D ring, which allows access to a number of potentially active cytotoxic intermediates en route to the final compound. The preliminary in vitro results of two such compounds are also included with the racemic title compound exhibiting cytotoxicity in the nanomolar range.",10.1021/ja805936v,2008-11-17,0.6188325894680899
Tetrahedron,"Asymmetric synthesis of a key 1α,25-dihydroxy-vitamin D3 ring a synthon",,10.1016/0040-4039(93)88021-a,1992-12-01,0.6188284840853052
Organic Letters,A Synthesis of the Carbon Skeleton of Erectcyanthin C,"The stereoselective asymmetric synthesis of the tricyclic skeleton of erectcyanthin C, a cyathane diterpenoid exhibiting anti-dyslipidemic activity, is reported. The synthetic strategy features the regioselective formation of vinyl triflate through Sakurai allylation/reductive debromination followed by gold-catalyzed stereoselective Nazarov cyclization and late-stage ring-closing metathesis.",10.1021/acs.orglett.5c02880,2025-08-21,0.618815711237858
Organic Letters,Expanding Access to Remdesivir via an Improved Pyrrolotriazine Synthesis: Supply Centered Synthesis,"is an important precursor to remdesivir. Initial results toward an efficient synthesis are disclosed consisting of sequential cyanation, amination, and triazine formation beginning from pyrrole. This route makes use of highly abundant, commoditized raw material inputs. The yield of triazine was doubled from 31% to 59%, and the synthetic step count was reduced from 4 to 2. These efforts help to secure the remdesivir supply chain.",10.1021/acs.orglett.0c02848,2020-09-15,0.6187895353783908
Tetrahedron,"Synthesis of (S,S)-3-prolylazetidin-2-one: A key component in the synthesis of an HIV gp120 constrained immunogen",,10.1016/0040-4039(95)02340-2,1996-02-01,0.6187862282168107
Organic Letters,Stereocontrolled Synthesis of the Tricyclic ABC Ring System of Daphnicyclidin A,"An enantiocontrolled synthesis pathway has been developed to provide formation of tricyclic amine 7, representing the ABC ring system of the complex alkaloid daphnicyclidin A (1). Our efforts describe preparation of the Z-hexahydro-(1H)-azocine 29 and cyclization to construct the novel 4-azabicyclo[5.3.2]dodecane 31. Transannular reductive amination following the deprotection of 31 gave the desired tertiary amine 7.",10.1021/ol5005092,2014-03-27,0.6187769467127071
Synlett,A Concise Total Synthesis of Steroid Scaffolds via a Palladium-Catalyzed Dearomatization Cyclization,"Abstract A concise total synthesis to generate synthetically challenging steroids scaffolds is reported utilizing palladium-catalyzed dearomatization cyclization for the key cyclization step, enabling the divergent synthesis of 6,6,6,5-tetracyclic steroids cores through both ligand and reaction condition control. We have started from the simple starting materials 2,4,6-trihydroxybenzoic acid and 2-methylcyclopentane-1,3-dione to selectively generate complex steroid scaffolds in a 12-step operation.",10.1055/s-0042-1751356,2022-08-19,0.6187749339082961
Journal of the American Chemical Society,Total Synthesis of the Acetyl CoA Carboxylase Inhibitor Soraphen A: Asymmetric Tsuji Reduction Enables Successive Olefin Metathesis,"The total synthesis of soraphen A, a myxobacterial metabolite and inhibitor of acetyl CoA carboxylase, was completed in 11 steps (longest linear sequence), less than half the steps previously required. Seven metal-catalyzed processes were deployed to unlock step-economy (comprising five asymmetric processes and four C-C bond formations). The present route does not utilize chiral auxiliaries, and four of five C-C bond formations exploit non-premetalated partners. To maximize convergency, an asymmetric Tsuji reduction was developed using a Pd-AntPhos catalyst that allows a metathesis-inactive allylic carbonate to serve as a masked terminal olefin, thereby enabling successive olefin metathesis events.",10.1021/jacs.1c12063,2022-01-10,0.6187668790955431
Journal of Organic Chemistry,"A Chiron Approach to the Total Synthesis of (−)-Juglomycin A, (+)-Kalafungin, (+)-Frenolicin B, and (+)-Deoxyfrenolicin","A general, efficient, and common strategy for the synthesis of (-)-juglomycin A, (+)-kalafungin, (+)-frenolicin B, and (+)-deoxyfrenolicin is reported here. The strategy involves the synthesis of a key building block alkyne from a cheap chiral pool material, D-glucono-δ-lactone, Dötz benzannulation, oxa-Pictet-Spengler reaction, and H(2)SO(4)-mediated epimerization.",10.1021/jo3019939,2012-10-22,0.6187653159201721
European Journal of Organic Chemistry,The Shortest (Four‐Step) Total Synthesis of the Eight‐Membered Cyclic Ether (<i>rac</i>)‐ and (–)‐<i>cis</i>‐Lauthisan,Abstract Access to the eight‐membered cyclic ether ( rac )‐ and (–)‐ cis ‐lauthisan was achieved in two complementary ways in only four steps for the longest linear sequence by starting from commercially available materials. The sequence features a cis ‐stereoselective reductive cyclization as the key step.,10.1002/ejoc.201301042,2013-08-22,0.6187565683547848
Synthesis,Synthesis of Triketide δ-Lactones,An efficient synthetic route was developed to prepare substituted δ-lactones 1 and 2 in enantiopure forms which are potentially useful for biosynthetic studies with genetically engineered modular polyketide synthase (PKS). The key step to prepare the target epimeric lactones involves the samarium(II) iodide-mediated Reformatsky reaction.,10.1055/s-2001-17514,2001-01-01,0.618751758824104
Tetrahedron,A novel synthetic method of HMG-CoA reductase inhibitor NK-104 via a hydroboration-cross coupling sequence,,10.1016/s0040-4039(00)61407-7,1993-12-01,0.6187462688961135
Chemical Science,Enantioselective total synthesis of (+)-cylindricine B,A concise enantioselective synthesis of the marine alkaloid (+)-cylindricine B proceeds in 5 or 6 steps and hinges on dearomative retrosynthetic logic.,10.1039/d4sc04910a,2024-01-01,0.6187384799528285
Synthesis,Efficient Synthesis of the Immunomodulating Compound KRP-203,A practical and concise synthesis of KRP-203 (1) was achieved by utilizing a palladium coupling reaction mediated by XantPhos and Pd2(dba)3 as the key step. The coupling reaction of aryl bromide 5 with 3-hydroxythiophenol (6) proceeded chemoselectively to give phenol 7 in spite of the presence of a chlorine substituent on 5 and a hydroxyl group on 6. Phenol 7 was converted into KRP-203 by benzylation and removal of the protecting groups in high yield.,10.1055/s-2007-983721,2007-06-26,0.6187329735687467
Tetrahedron,A practical total synthesis of gelastatins,,10.1016/s0040-4039(03)01407-2,2003-07-01,0.618731044058481
Tetrahedron,A practical total synthesis of (+)-isogalbulin and (+)-galbulin,,10.1016/j.tetlet.2014.09.090,2014-09-28,0.618731044058481
Organic Letters,Total Synthesis and Initial Biological Evaluation of New B-Ring-Modified Bryostatin Analogs,"[Structure: see text] The total synthesis and preliminary biological evaluation of the first bryostatin analogs (bryologs) to incorporate B-ring substitution are reported. Asymmetric syntheses of two new polyketide ""spacer"" domains are described, one exploiting the pseudosymmetry of the C1-C13 region. These fragments are convergently joined to the ""recognition"" domain through a remarkably versatile macrotransacetalization process. The resulting new analogs exhibit potent nanomolar or picomolar affinity to protein kinase C (PKC), comparable to or better than that found for bryostatin.",10.1021/ol0620904,2006-10-20,0.6187272042608943
Organic Process Research & Development,"An Alternate, Efficient Synthetic Process for a Hemolytic Anemia Drug: Mitapivat Sulfate","A new commercial manufacturing process for producing mitapivat sulfate, crucial for treating hemolytic anemia, is described. Starting from 4-nitrobenzoic acid ( 14 ) and N-Boc piperazine ( 6 ), the process involves sequential reactions to obtain tert -butyl 4-[4-(quinoline-8-sulfonamido)benzoyl]piperazine-1-carboxylate ( 7 ). This compound is then deprotected to yield N -[4-(piperazine-1-carbonyl)phenyl]naphthalene-1-sulfonamide ( 8 ), which undergoes reductive amination to produce mitapivat-free base ( 9 ). Finally, mitapivat sulfate is obtained with high quality and an overall yield of 81%. The synthesis prevents impurity formation and employs cost-effective raw materials, adhering to environmental sustainability and ICH product quality standards.",10.1021/acs.oprd.4c00319,2024-10-16,0.618723951462969
Synlett,"Regioselective Synthesis of Furan-Fused 3-Hydroxy-2,2-dimethylchroman, NG-121 Model Compound","Regioselective synthesis of the model compound of NG-121 was achieved. The key steps are ortho-alkylation of the phenol via [2,3]sigmatropic rearrangement of a sulfur ylide and the regio­selective construction of the attached lactone ring.",10.1055/s-2006-941561,2006-05-22,0.6187127396288251
Organic Process Research & Development,Development of an Intrinsically Safer Methanolysis/Aromatic Nitro Group Reduction for Step 1 and 2 of Talazoparib Tosylate,"A change in facility for the synthesis of the step 2 intermediate for talazoparib tosylate ( 1 · TsOH ) required the development of an alternative, intrinsically safer process. Rapid route scouting and considerations of process safety enabled the development of a telescoped two-step process that was demonstrated on a multikilogram scale.",10.1021/acs.oprd.1c00259,2021-11-18,0.6187103238248893
Journal of Organic Chemistry,Novel Syntheses of 2-Butyl-5-chloro-3<i>H</i>-imidazole-4-carbaldehyde:  A Key Intermediate for the Synthesis of the Angiotensin II Antagonist Losartan,"Reaction of glycine methyl ester (19) with imidate 18 under carefully optimized conditions allowed preparation of the rather unstable imidazolinone 11 in ca. 90% yield. Reaction of 11 with POCl(3)/DMF followed by aqueous workup gave aldehyde 2, a key intermediate for the synthesis of the angiotensin II antagonist Losartan, in ca. 55% yield. Structural identification of intermediates and byproducts formed during both the reaction to prepare 11 and the reaction of 11 with POCl(3)/DMF allowed development of several closely related syntheses of aldehyde 2.",10.1021/jo9824910,1999-10-01,0.6187068718739519
Synthesis,"An Efficient Approach for the Synthesis of 1′-O-α-Methyl Pyrrolo[2,3-d]pyrimidine Isonucleosides","A series of novel 1′-O-α-methyl isonucleosides were efficiently and stereoselectively synthesized with 1,2,3,5-tetra-O-acetyl-d-ribofuranose as the starting material. The key steps include regioselective and stereoselective deprotection of the 2,4-dichlorobenzyl group at C2, triflation, and substitution with appropriate nucleobases using cesium carbonate as the base. Removal of the residual 2,4-dichlorobenzyl groups and subsequent transformation afforded the title compounds in 30-37% overall yield. The products represent a new type of isonucleosides with 1′-O-substitution.",10.1055/s-0030-1259961,2011-03-16,0.6186958104771132
European Journal of Organic Chemistry,Linear Synthesis of Chiral <i>cyclo</i>Sal‐Pronucleotides,"Abstract Cyclo Sal‐nucleosyl‐phosphate triesters are a known class of highly effective nucleotide prodrugs (pronucleotides) of antivirally active nucleoside analogues. Until recently, the synthesis of these compounds always gave diastereoisomeric mixtures. Then, a convergent route for the stereospecific synthesis of cyclo Sal‐triesters was described to give isomerically pure cyclo Sal‐prodrugs for the treatment of viral diseases. Here, the development of a stereoselective synthesis of these pronucleotides using various chiral auxiliaries is described. In contrast to pyrrolidine‐ or pyrrolidinone derivatives it was found that a thiazolidine derived from valinol fulfilled all three requirements to act as a suitable chiral moiety, allowing: (i) strong chirality transfer, (ii) the formation of separable diastereoisomeric intermediates, and (iii) a suitable leaving group that allows the introduction of the nucleoside analogue (e.g., d4T) in the final step under mild reaction conditions. The title compounds were obtained with very high diastereoisomeric excesses of more than 95 %.",10.1002/ejoc.201100334,2011-06-06,0.6186908033466461
Tetrahedron,The synthesis of substituted benzophenalenofurans a novel pentacyclic ring system,,10.1016/s0040-4039(01)92654-1,1977-01-01,0.618690360655613
Synthesis,A Short Synthesis of Partially Protected l- and d-β-Hydroxyenduracididines and a Structurally Simplified Dipeptide Analogue,"A short synthesis of the C2-epimeric amino acids l - and d -β-hydroxyenduracididine (βhEnd) was developed. Both amino acids are part of the cyclopeptide portion of the mannopeptimycin antibiotics. The synthetic route comprises eight steps starting from Garner’s aldehyde and provides partially protected derivatives in good overall yields. Key steps are a stereodivergent olefination–bishydroxylation sequence and a regioselective guanidine cyclization reaction. In addition, precursor amino acids that contain a protected amino alcohol instead of the cyclic guanidine could be efficiently coupled to provide a structurally simplified analogue of the l -βhEnd- d -βhEnd dipeptide portion of the mannopeptimycin aglycone.",10.1055/s-0033-1341236,2014-05-16,0.6186821471744397
Tetrahedron,A highly efficient and enantioselective synthesis of EEHP and EMHP: intermediates of PPAR agonists,,10.1016/j.tetlet.2016.06.093,2016-06-23,0.6186722312474547
European Journal of Organic Chemistry,Flexible Stereo‐ and Regioselective Synthesis of <i>myo</i>‐Inositol Phosphates(Part 1): Via Symmetrical Conduritol B Derivatives,"Abstract A practical route is described for the preparation of myo ‐inositol polyphosphates. Optically pure myo ‐inositol derivatives can be prepared from p ‐benzoquinone in both forms by enzymatic resolution of a C 2 ‐symmetric diacetoxyconduritol B key intermediate, followed by cis ‐dihydroxylation. Selective functionalization of axial and equatorial hydroxy groups allows the synthesis of symmetric inositol phosphates as well as unsymmetrical, enantiomerically pure inositol phosphates. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2005)",10.1002/ejoc.200400911,2005-07-01,0.6186719394797701
Synlett,"Asymmetric Synthesis of 2,3,6-Trisubstituted Piperidines via Baylis–Hillman Adducts and Lithium Amide through Domino Reaction","A convenient asymmetric synthesis of methyl (2S,3S,6R)-6-(4-fluorophenyl)-2-(4-hydroxyphenyl)-piperidine-3-carboxylate is described, starting from Baylis–Hillman adducts. The route involves a domino process: allylic acetate rearrangement, stereoselective Ireland–Claisen rearrangement and asymmetric Michael addition, which provides a δ-amino acid derivative with full stereochemical control. A subsequent chemoselective transformation of one of the side-chain groups allows an effective cyclization leading to biologically interesting polysubstituted piperidines in which the 2,6-aryl groups could be attached sequentially.",10.1055/s-0039-1690990,2019-09-24,0.6186611526024165
Organic Letters,"Synthesis of the Taxol Core via Catalytic Asymmetric 1,4-Addition of an Alkylzirconium Nucleophile","The Taxol core was prepared in five steps via a key copper-catalyzed asymmetric conjugate addition trapping sequence. The use of a bromodiene-derived alkylzirconium nucleophile followed by trapping with POCl 3 /DMF gave a highly functionalized intermediate featuring a quaternary center in 69% yield with 92% ee. After 1,2-addition, Suzuki–Miyaura cross-coupling, allylic oxidation, and a type II intramolecular Diels–Alder reaction, the taxol core was obtained in 11% overall yield with 92% ee.",10.1021/acs.orglett.0c01165,2020-05-12,0.6186569354877423
Tetrahedron,An efficient synthesis of the naphthalene moiety of neocarzinostatin chromophore,,10.1016/s0040-4039(01)80337-3,1989-01-01,0.6186542170388419
Synlett,An Efficient Formal Synthesis of Aflatoxin B2 by Use of the Kikuchi Rearrangement Reaction,"All articles of this category A five-step, highly efficient synthesis of tetrahydrofurobenaofuran 2 , the pivotal intermediate in the synthesis of aflatoxin B 2 , has been achieved in 24% (40% on the basis of the recovered aldehyde for the Wittig conversion of 5a to 4a ) overall yield from 5a . The key chain-branching step that provided the tetrahydrobisfuran carbon framework has been achieved by use of the Kikuchi rearrangement reaction, i.e., treatment with I 2 , Ag 2 O, dioxane/H 2 O of the styrene system 4b .",10.1055/s-1993-22526,1993-01-01,0.6186493060558714
Journal of Organic Chemistry,"A Concise Asymmetric Synthesis of (2<i>S</i>,3<i>S</i>,7<i>S</i>)-3,7-Dimethylpentadecan-2-yl Acetate and Propionate, the Sex Pheromones of Pine Sawflies","(2S,3S,7S)-3,7-Dimethylpentadecan-2-yl acetate (2) and its propionate analogue (3) are the main sex pheromones of all Neodiprion species and Diprion similes, respectively. Starting from (S)-malic acid and employing a highly chemo-, regio-, and stereoselective tandem ester reduction-epoxide formation-reductive epoxide-opening reaction protocol, an efficient total synthesis of (2S,3S,7S)-2 and -3 is reported herein.",10.1021/jo0497961,2004-04-27,0.6186471323454905
Synlett,Synthetic Studies on Poison-Frog Alkaloid 261C,The synthesis of highly substituted indolizidine core for the synthesis of poison-frog alkaloid 261C has been achieved.,10.1055/s-2005-921911,2005-01-01,0.6186435013459464
Journal of Organic Chemistry,New Tin Templates for the Synthesis of Macrocyclic Polythiaether−Polythiaester Ligands,"The preparation of new tin templates, stannathianes 1-3 is described. New templates have been successfully applied to the synthesis of macrocyclic polythialactones 4-9 by cyclization of corresponding stannathianes 1-3 with pimeloyl dichloride.",10.1021/jo048712l,2004-11-01,0.6186381317151572
Journal of the American Chemical Society,Enantioselective Total Synthesis of Plectosphaeroic Acid B,"The first total synthesis of a member of the plectosphaeroic acid family of fungal natural products is reported. Key steps include the late-stage formation of the hindered N6-C9"" bond and stereoselective introduction of the two methylthio substituents.",10.1021/ja401423j,2013-03-04,0.6186340733599093
Journal of Organic Chemistry,Enantioselective Synthesis of 5-LO Inhibitor Hydroxyureas. Tandem Nucleophilic Addition−Intramolecular Cyclization of Chiral Nitrones,"An enantioselective synthesis of chiral hydroxyurea based 5-lipoxygenase inhibitors is reported via a five-step sequence in about 30% overall yield. The synthesis is based on a novel tandem nucleophilic addition−intramolecular cyclization reaction in which a chiral nitrone functions as the electrophilic acceptor species. A mannose-based chiral auxiliary controls the diastereoselectivity of the reaction in an 8:1 ratio. After the auxiliary removal and appropriate functionalization, a single recrystallization afforded the target structures in >99% ee.",10.1021/jo9621736,1997-08-01,0.6186262781883936
Synlett,"First Total Synthesis of Caminoside A, an Antimicrobial Glycolipid from Sponge","Caminoside A, a novel antimicrobial tetrasaccharide glycolipid from the marine sponge Caminus sphaeroconia, which represents the first bacterial type III secretion inhibitor, is synthesized in a total of 57 steps starting from D-glucose, D-galactose, L-rhamnose, and 9-decenal.",10.1055/s-2004-837221,2005-01-01,0.6186177054759695
Tetrahedron,Conformationally constrained thyroliberin analogs: a novel electrochemical route to a key rigid Pro-Phe building block,,10.1016/s0040-4039(00)79559-1,1992-05-01,0.6186096253949567
European Journal of Organic Chemistry,An Efficient Asymmetric Synthesis of Finerenone via Evans’ Chiral Auxiliary,"This article reports a new application of Evans’ chiral auxiliary for an efficient asymmetric synthesis of finerenone. This new application successfully achieves the key step of stereoselective construction of the naphthyridine core of finerenone, with a high diastereomeric ratio (dr 86:14) and an 80% yield of the desired product via Evans’ chiral (R)‐4‐benzyl‐2‐oxazolidinone. The downstream transamidation of ethyl ester, with ammonia, leads to the formation of finerenone.",10.1002/ejoc.202500538,2025-06-11,0.6186051074555821
Journal of the American Chemical Society,Total Synthesis of the Potent Anticancer Aglaia Metabolites (−)-Silvestrol and (−)-Episilvestrol and the Active Analogue (−)-4′-Desmethoxyepisilvestrol,"Total synthesis of the anticancer 1,4-dioxane containing natural products silvestrol (1) and episilvestrol (2) is described by an approach based on the proposed biosynthesis of these novel compounds. The key steps included an oxidative rearrangement of the protected d-glucose derivative 11 to afford the 1,4-dioxane 12, which could be elaborated to the coupling partner 5 and a photochemical [3 + 2]-cycloadditon between the 3-hydroxyflavone 27 and methyl cinnamate followed by base-induced alpha-ketol rearrangement and reduction to give the cyclopentabenzofuran core 33. The core (-)-6 and 1,4-dioxane fragment 5 were united by a highly stereoselective Mitsunobu coupling with the modified azodicarboxylate DMEAD to afford the axial coupled product 36. Deprotection then gave episilvestrol (2). Silvestrol (1) was synthesized by a coupling between core (-)-6 and the dioxane 44 followed by deprotection. Compound 1 was also synthesized from episilvestrol (2) by a Mitsunobu inversion. In addition, the analogue 4'-desmethoxyepisilvestrol (46) was synthesized via the same route. It was found that 46 and episilvestrol 2 displayed an unexpected concentration-dependent chemical shift variation for the nonexchangeable dioxane protons. Synthetic compounds 1, 2, 38, 46, and 54 were tested against cancer cells lines, and it was found that the stereochemistry of the core was critical for activity. Synthetic analogue 4'-desmethoxyepisilvestrol (46) was also active against lung and colon cancer cell lines.",10.1021/ja808402e,2009-01-13,0.6186001848152786
Journal of Organic Chemistry,Expanding the Boxmi Ligand Family: Synthesis and Application of NON and NSN Ligands,"Two synthetic strategies for a new family of neutral NON ligands featuring a “bis(oxazolinylmethylidene)isobenzofuran” framework (boxman) are reported. A Pd-mediated cyclization reaction forming the isobenzofuran core constitutes the key reaction in the eight-step synthetic route to the nonbackbone-methylated target compound H,R boxman. In contrast, the introduction of two additional methyl groups provides stereochemical control during backbone construction and thereby access to the methylated derivative Me,R boxman, which was synthesized in five steps and improved yields. In addition, the synthetic sequence was transferred to the thio analogue, providing access to the NSN ligand H,R boxmene. Subsequent complexation experiments with iron and cobalt chloride precursors afforded the four-coordinated chlorido complexes Me,R boxmanMCl 2 (R = Ph, i Pr; M = Fe, Co) and established the boxman family as trans -chelating, bidentate bis(oxazoline) ligands. Application of the latter in the nickel(II)- and zinc(II)-catalyzed α-fluorination of β-ketoesters and oxindoles (up to 98% yield and 94% ee) demonstrated their suitability for enantioselective catalysis.",10.1021/acs.joc.0c00751,2020-04-14,0.6185862412815983
Journal of Organic Chemistry,"Concise Synthesis and Biological Evaluation of the Pyrrolo[4,3,2-<i>de</i>]quinoline Core of the Lymphostin Family","The efficient synthesis of the pyrrolo[4,3,2- de ]quinoline core of the lymphostin family (compound 1 ) has been accomplished in 7 steps and 18.6% overall yield, providing an efficient method for the total synthesis and structural modification of the lymphostin family. Compound 1 showed potent inhibitory activities against PI3K/mTOR in the nanomolar range and activity against human colorectal cancer cell lines comparable to that of oxaliplatin, which could be recognized as a novel lead compound for cancer therapy.",10.1021/acs.joc.4c02038,2024-10-23,0.6185861024647381
Journal of Organic Chemistry,"Synthesis of Bi-, Ter-, and Quaterpyridinecarboxylates via Propargylisoxazole–Pyridine Rearrangement","A flexible method was developed for the synthesis of 2,2'-bi-, 2,2':6',2″-ter-, and 2,2':6',2'':6'',2‴-quaterpyridines containing a nicotinic acid moiety. The approach involves the Fe(II)/Au(I)-catalyzed rearrangement of key 4-propargylisoxazole building blocks bearing a pyrid-2-yl or quinolin-2-yl substituent at the 3-position and Pd(0)-catalyzed cross-coupling reactions.",10.1021/acs.joc.0c00611,2020-04-08,0.6185830189675008
Organic Letters,Total Synthesis of (±)-Lepadiformine via an Amidoacrolein Cycloaddition,"[reaction: see text]. The total synthesis of the cytotoxin lepadiformine is described. The intermolecular cycloaddition of a 2-amidoacrolein with the dimethyl acetal of 4,6-heptadienal gave a cycloadduct that was strategically functionalized for elaboration of the tricyclic ring system. These steps include a diastereoselective addition of an organoytterbium reagent to an aldehyde, cyclization to the trans-perhydroquinoline substructure via a Mitsunobu reaction, and an iodine-promoted amine cyclization with an alkene to introduce the pyrrolidine ring.",10.1021/ol0165903,2001-10-02,0.6185675053882204
Synthesis,"Toward a Total Synthesis of Okilactomycin. 1. A Direct, Enantiocontrolled Route to the Western Sector","A synthesis of the western half of the macrocyclic ring framework of the antitumor antibiotic okilactomycin is described. The strategy employed rests on an efficient synthesis of meso-2,4-dimethylglutaric anhydride and ensuing resolution via reaction with (S)-(-)-α-methylbenzylamine, diborane reduction, and selective crystallization. Following acid-catalyzed cyclization to (2S,4R)-2,4-dimethyl-δ-valerolactone, an acyclic stereocontrol strategy was adopted to achieve chain lengthening with appropriate incorporation of functionality. The sensitive aldehyde 2 was further homologated to β-keto ester 17 in a model reaction sequence performed to simulate its ultimate projected coupling to 3.",10.1055/s-2002-28510,2002-01-01,0.618565899008525
Tetrahedron,Symmetrical doubly connected head-to-head α-cyclodextrin dimers: a high yield synthesis of a novel type of neoglycolipid,,10.1016/s0040-4039(02)01125-5,2002-08-01,0.61856299504672
Angewandte Chemie International Edition,Bioinspired Total Synthesis of (+)‐Euphorikanin A,"We have achieved a bioinspired total synthesis of (+)-euphorikanin A, which possesses an intriguing and complex 5/6/7/3-fused tetracyclic skeleton bearing a bridged [3.2.1]-γ-lactone moiety. Key transformations include stereoselective alkylation and aldol condensation to install the main stereocenters, an intramolecular nucleophile-catalyzed aldol lactonization of carboxylic acid-ketone to assemble the five-membered ring, a McMurry coupling to construct the seven-membered ring, and a biomimetic benzilic acid type rearrangement to form the bridged [3.2.1]-γ-lactone moiety.",10.1002/anie.202200576,2022-02-15,0.6185563005540415
Synlett,"One-Pot Coupling–Cyclization–Alkylation Synthesis of 1,2,5-Trisubstituted 7-Azaindoles in a Consecutive Three-component Fashion","1,2,5-Trisubstituted 7-azaindoles are rapidly and efficiently prepared in a one-pot, copper-free alkynylation–cyclization–alkylation sequence starting from unprotected 2-aminopyridyl halides in a consecutive three-component fashion. By extension to a consecutive four-component coupling–cyclization–iodination–alkylation synthesis of 3-iodo-1-methyl-2-phenyl-1H-pyrrolo[2,3-b]pyridine, a concise synthesis of SIS3, a selective TGF-β1 and signaling inhibitor, was realized.",10.1055/s-0036-1590837,2017-07-24,0.6185524255537888
European Journal of Organic Chemistry,A Concise Stereoselective Total Synthesis of Methoxyl Citreochlorols and Their Structural Revisions,"Abstract A concise, stereoselective and protecting group free approaches for the total synthesis of (−)‐(2 S ,4 R )‐ and (+)‐(2 R ,4 S )‐3′‐methoxyl citreochlorols and their stereoisomers are demonstrated. All four stereoisomers were synthesized to establish the absolute stereochemistry of the reported structures and the structures were revised accordingly. The approach involves chelation controlled regioselective reduction of a diester, silyl iodide promoted ring‐opening iodo esterification of lactones, highly chemo‐ and regioselective ring‐opening of an epoxy ester, dichloromethylation of a carboxyl group, and syn ‐ and anti ‐selective reduction of the resulted β ‐hydroxy ketone as key steps.",10.1002/ejoc.202001563,2021-02-19,0.6185411756932905
Organic Process Research & Development,A Three-Step Synthesis of Acotiamide for the Treatment of Patients with Functional Dyspepsia,"A three-step synthesis of acotiamide is described. The agent is marketed in Japan for treatment of patients with functional dyspepsia. We designed a one-pot method to prepare the key intermediate 5a from 2 via an acyl chloride and amide and then reacted with 6 to obtain 1 under solvent-free condition. With the use of DCC, the unavoidable impurity 5b was also successfully converted into the desired 1 . After isolation of 1, we carried forward to the next step of HCl salt formation, which was proved to be a very effective procedure for the removal of practically all major impurities. The process is cost-effective, simple to operate, and easy to scale-up.",10.1021/acs.oprd.5b00256,2015-11-13,0.6185275322624392
Synthesis,"A Multigram, Catalytic and Enantioselective Synthesis of Optically Active 4-Methyl-2-cyclohexen-1-one: a Useful Chiral Building Block","All articles of this category The first catalytic asymmetric synthesis of both ( R )-(+)- and ( S )-(-)-4-methyl-2-cyclohexen-1-one and a new and improved synthesis of both enantiomers of (1 S ,4 S )-(-) and (1 R ,4 R )-(+)-4-methyl-2-cyclohexen-1-ol was developed on a multigram scale. The key step of this approach is the asymmetric catalyzed addition of Me 2 Zn (S N 2′-pathway) to racemic 1,3-cyclohexadiene monoepoxide. This step has been optimized as for as enantio- and regioselectivities, and work-up procedures. The striking ligand accelerated catalysis exhibited by the chiral copper complex of the 2,2′-binaphthyl-based phosphoramidite, herein reported, permitted a very low catalyst loading (0.6 mol%). enantiomer resolution - scale-up - catalysis - organozinc reagent - copper",10.1055/s-2001-11445,2001-01-01,0.6185162091785621
Tetrahedron,"The first selective one-pot synthesis of 1,3-dicarbonyl adamantanes from adamantane and 1,3-dimethyladamantane",,10.1016/j.tetlet.2012.04.125,2012-05-02,0.6184909298088137
Tetrahedron,"Selectivity between N-1 and N-7 nucleosides: regioselective synthesis of BMK-Y101, a potent cdk7 and 9 inhibitor",,10.1016/j.tetlet.2013.07.132,2013-08-02,0.6184870102681508
Journal of Organic Chemistry,Chemoenzymatic Synthesis of Vitamin B5-Intermediate (<i>R</i>)-Pantolactone via Combined Asymmetric Organo- and Biocatalysis,"The combination of an asymmetric organocatalytic aldol reaction with a subsequent biotransformation toward a ""one-pot-like"" process for the synthesis of (R)-pantolactone, which to date is industrially produced by a resolution process, is demonstrated. This process consists of an initial aldol reaction catalyzed by readily available l-histidine followed by biotransformation of the aldol adduct by an alcohol dehydrogenase without the need for intermediate isolation. Employing the industrially attractive starting material isobutanal, a chemoenzymatic three-step process without intermediate purification is established allowing the synthesis of (R)-pantolactone in an overall yield of 55% (three steps) and high enantiomeric excess of 95%.",10.1021/jo502667x,2015-02-24,0.6184857610682265
Journal of the American Chemical Society,Total Synthesis and Properties of the Crambescidin Core Zwitterionic Acid and Crambescidin 359,"The total synthesis of the crambescidin core acid 9, crambescidins 359 (8) and 431 (7), and the properties of the crambescidin core are described. A key step of the synthetic route to guanidinium carboxylate 9 is Pd(0) catalyzed cleavage of the ester side chain of pentacyclic cinnamyl ester 15. This ester is also employed to prepare a small library of crambescidin alkaloid analogues that differ in their C14 side chain. The zwitterionic guanidinium carboxylate 9 was shown to readily decarboxylate to form crambescidin 359 (8). Decarboxylation of crambescidin core acid 9 was fastest under basic conditions. In the presence of base, up to eight deuterium atoms can be incorporated into the pentacyclic crambescidin core. Both deuterium incorporation and decarboxylation of crambescidin core acid 9 are the result of facile ring opening of the spirocyclic ether rings of the pentacyclic guanidinium moiety.",10.1021/ja042875+,2005-02-18,0.6184854488478212
Tetrahedron,Synthesis of an inhibitor of sphingosine-1-phosphate lyase,,10.1016/s0040-4039(00)75971-5,1994-01-01,0.6184830632870854
Tetrahedron,Novel stereoselective route to cis-chrysanthemic acid,,10.1016/s0040-4039(00)82293-5,1988-01-01,0.6184720052979106
Organic Process Research & Development,"Complementary Syntheses of <i>N</i>,<i>O</i>-Protected-(<i>S</i>)-2-methylserine on a Multikilogram Scale","Two complementary and scalable approaches have been used to manufacture multikilogram quantities of N, O -protected-( S )-2-methylserine. The first approach uses a diastereomeric salt resolution of 2-methylserine methyl ester as the (1 S )-(+)-camphorsulfonate salt, and was used to rapidly access 15 kg of ( S )-3- tert -butoxycarbonyl-2,2,4-trimethyl-1,3-oxazolidine-4-carboxylic acid with >99% ee. The second approach involves a stereoselective enolate methylation of a chiral cyclic l -serine derivative under cryogenic conditions. The four-step telescoped process, starting from l -serine methyl ester, was used to manufacture 20 kg of (2 R,4 S )-2- tert -butyl-3- tert -butoxycarbonyl-4-methyl-1,3-oxazolidine-4-carboxylic acid in 52% overall yield and 98% ee. The advantages and disadvantages for scale-up of both approaches are discussed.",10.1021/op100299d,2011-01-18,0.618461313255047
Organic Letters,Formal Chemoselective Synthesis of Leucascandrolide A,"A chemoselective synthesis of the macrocyclic core of leucascandrolide A has been achieved, utilizing highly enantioselective allylmetalations, an enantioselective Noyori reduction of a propargylic ketone and olefin metatheses as the key steps.",10.1021/ol070670a,2007-05-31,0.6184565641049531
Tetrahedron,A new asymmetric synthesis of (S)-(+)-pipecoline and (S)-(+)- and (R)-(−)-coniine by reductive photocyclization of dienamides,,10.1016/s0040-4039(00)01549-5,2000-11-01,0.6184524672566437
Journal of Organic Chemistry,Explorations on the Total Synthesis of the Unusual Marine Alkaloid Chartelline A,"In work directed toward a total synthesis of chartelline A (1a), a strategy was investigated to construct the 10-membered ring of this marine alkaloid via an intramolecular aldehyde/beta-lactam cyclocondensation to form the macrocyclic enamide functionality. Therefore, spiro-beta-lactam and imidazole fragments were first prepared. Tribromooxindole beta-lactam 24 was synthesized from commercially available 5-nitroisatin (18) in seven steps and 30% overall yield via a Staudinger ketene-imine [2 + 2]-cycloaddition strategy. The requisite 2-bromoimidazole subunit 40 bearing a terminal alkyne and a masked aldehyde was efficiently prepared from the readily available imidazole ester 25 in 10 steps. With both advanced intermediates available, the addition of the lithium acetylide generated from 2-bromoimidazole subunit 40 to the gamma-lactam carbonyl group of N-Boc-tribromooxindole 24 was investigated, affording the desired N-Boc-aminal 41. Hydrolysis of the acetonide moiety of 41, followed by oxidative cleavage of the resulting diol, gave the aldehyde 42. Unfortunately, treatment of aldehyde 42 with p-toluenesulfonic acid did not give the desired 10-membered macrocyclic (Z)-enamide 46, but rather the highly unsaturated seven-membered ring compound 44.",10.1021/jo060084f,2006-03-07,0.6184515886529922
Journal of Organic Chemistry,"Total Synthesis of (−)-Platensimycin, a Novel Antibacterial Agent","An enantioselective synthesis of platensimycin, a novel antibiotic natural product that inhibits bacterial beta-ketoacyl-(acyl-carrier-protein) synthase (FabF), is described. Our synthetic strategy for the construction of the oxatetracyclic core involved an intramolecular Diels-Alder reaction. Our preliminary studies provided a complex tetracyclic product by first undergoing an interesting 1,5-hydride shift followed by a Diels-Alder reaction. Further optimization of the diene's electronic properties, by incorporation of a methoxy group, led to the oxatetracyclic core of platensimycin. The three required chiral centers, including two all-carbon quaternary chiral centers, were built in the intramolecular Diels-Alder step. The synthesis utilized natural (+)-carvone as the key chiral starting material, which determined the stereochemistry of the final product. The synthesis also featured an efficient Petasis olefination, a hydroboration sequence, a Gais's asymmetric Horner-Wadsworth-Emmons reaction, and a mercury salt catalyzed enol ether isomerization.",10.1021/jo802261f,2009-01-05,0.6184487591443744
Organic Letters,A New Synthetic Route to Phomoidride B and Its Derivatives,"We have developed a new synthetic route to phomoidride B, which could also be applied to the synthesis of phomoidride B derivatives using Pd-catalyzed coupling reaction of a thiolester with an organozinc reagent. In addition, direct construction of the maleic anhydride moiety has been achieved by a Pd-catalyzed carbonylation reaction.",10.1021/ol034471c,2003-06-01,0.6184383032808748
Tetrahedron,"Structure and synthesis of WF 3681, a novel aldose reductase inhibitor",,10.1016/s0040-4039(00)84436-6,1986-01-01,0.6184302759834064
Synthesis,Synthesis of 3-Substituted Chromones and Quinolones from Enaminones,A facile and efficient synthetic route to 3-substituted chromones and quinolones was developed. Silver triflate was employed to activate the electrophile to react with various readily available enaminones.,10.1055/s-0035-1562513,2016-07-26,0.61842700624343
Journal of the American Chemical Society,Total Synthesis of Garsubellin A,"A concise approach to the laboratory synthesis of garsubellin A is described. Garsubellin A, an effective inducer of choline acetyltransferase (ChAT), has been shown to have potential as a therapeutic agent for the treatment of Alzheimer's disease. Starting from 3,5-dimethoxyphenol, the synthesis has provided garsubellin A in an 18-step sequence. Notable transformations include dearomative allylation, diastereoselective vinylogous lactonization, iodocarbocyclization, transannular Wurtz, and bridgehead functionalization reactions.",10.1021/ja057418n,2005-12-30,0.6184190239724935
Journal of Organic Chemistry,Total Synthesis and Cytotoxicity of Haterumalides NA and B and Their Artificial Analogues,"The total synthesis of haterumalides NA and B, potent cytotoxic marine macrolides, was achieved by using B-alkyl Suzuki-Miyaura coupling and Nozaki-Hiyama-Kishi coupling as key steps. Compared to our first-generation approach for ent-haterumalide NA methyl ester, this second-generation synthesis yielded much more of the key intermediate. This synthesis established the relative stereochemistry of haterumalide B. Furthermore, the structure-cytotoxicity relationships of haterumalides were investigated. The combination of macrolide and side chain parts proved to be important to the cytotoxicity.",10.1021/jo802806z,2009-04-03,0.618414212066437
Chemical Science,α-Diimine synthesis <i>via</i> titanium-mediated multicomponent diimination of alkynes with C-nitrosos,"the multicomponent coupling of Ti[triple bond, length as m-dash]NR imidos with alkynes and nitriles. The formation of α-diimines is achieved through formal [4 + 2]-cycloaddition of the C-nitroso to the Ti and γ-carbon of the diazatitanacyclohexadiene followed by two subsequent cycloreversion steps to eliminate nitrile and afford the α-diimine and a Ti oxo.",10.1039/d1sc06111a,2021-12-27,0.6184086387057657
Synlett,An Enantioselective Formal Total Synthesis of (-)-TAN1251A,"An enantioselective total synthesis of the muscarinic inhibitor (-)-TAN1251A has been achieved. An alkylidene 1,5-CH insertion reaction was used as a key step to produce a [5,5]-spirocyclic intermediate, which was transformed into the [6,5]-spirocyclic core of the natural product via an oxidative cleavage/aldol condensation sequence. The synthesis of the natural product was then completed using standard procedures.",10.1055/s-2004-829092,2004-01-01,0.6184023896339607
Organic Letters,A Scalable and Expedient Route to 1-Aza[6]helicene Derivatives and Its Subsequent Application to a Chiral-Relay Asymmetric Strategy,"A rapid route to diversely functionalized 1-aza[6]helicenes has been achieved via the development of a copper-mediated cross-coupling reaction, followed by PtCl4-catalyzed cycloisomerization. Not only does this method allow access to these functionally important molecules on gram scale, but this strategy is also suitable for relaying the axial chirality of a key intermediate to the helicity of the product.",10.1021/ol400493x,2013-03-21,0.6183958966197407
Journal of Organic Chemistry,"Total Synthesis of (+)-Chimonanthine, (+)-Folicanthine, and (−)-Calycanthine","Facile, straightforward, and asymmetric total syntheses of (+)-chimonanthine (1), (+)-folicanthine (2), and (-)-calycanthine (3) were accomplished in four to five steps from commercially available tryptamine. The synthesis features copper-mediated asymmetric cyclodimerization of chiral tryptamine derivative, which established a new entry into constructing the sterically hindered vicinal quaternary stereogenic carbon centers of dimeric hexahydropyrroloindole alkaloids in one procedure. An unprecedented base-induced isomerization from the chimonanthine skeleton to the calycanthine skeleton was observed and facilitated the synthesis of (-)-calycanthine (3).",10.1021/acs.joc.5b01907,2015-09-24,0.6183887148534776
Synthesis,"Rhodium Carbenoid Induced [1,2]-Migration in an l-Lyxo-Configured α-Diazo β-Keto Ester: Synthesis of a New Griseolic Acid Analogue","An appropriately substituted α-diazo β-keto ester, prepared from d-glucose, on treatment with a catalytic amount of dirhodium tetraacetate gave a strained 1,5-dioxabicyclo[3.3.0]octane ring system with concomitant diastereoselective formation of a quaternary carbon substituted with both an ethoxycarbonyl group and a 2-ethoxy-2-oxoethyl group; the product is a key intermediate in the synthesis of a new griseolic acid analogue.",10.1055/s-0029-1216835,2009-05-19,0.6183773834296672
Synthesis,Convenient Multigram Synthesis of (<i>R</i>)-Homopipecolic Acid Methyl Ester,"(R)-Homopipecolic acid methyl ester has been prepared on a multigram scale from 3,4-dihydro-2H-pyran in five steps and 36% overall yield. The stereochemistry was introduced via an asymmetric Michael addition and a fractional crystallization.",10.1055/s-2006-926419,2006-04-01,0.6183719381588462
Tetrahedron,A new stereo- and regioselective synthesis of (±)-sesamin involving a β-scission of alkoxyl radicals as the key step1,,10.1016/s0040-4039(00)79448-2,1991-10-01,0.6183711582885499
Journal of Organic Chemistry,Ti(II) and Rh(I) Complexes as Reagents toward a Thapsigargin Core,"A novel approach toward the [5-7]fused bicyclic core of thapsigargin, a subnanomolar inhibitor of the endo/sarcoplasmic calcium ATPase (SERCA), is presented. The synthetic route includes an original Ti(II)-mediated hydroxy-directed reductive coupling of an enantiomerically enriched propargylic alcohol and an intramolecular Rh(I)-catalyzed cyclocarbonylation reaction as key steps. Interestingly, through the first experiments of titanocene-mediated reductive cyclization of a 1,8-enyne, a seven-membered cycle was isolated as a unique product with a total diastereoselectivity.",10.1021/acs.joc.8b03249,2019-04-09,0.6183642921118954
Synthesis,A High Yield Route to Benzobarrelene and Substituted Derivatives,,10.1055/s-1975-23895,1975-01-01,0.6183642769912172
Organic Letters,Formal Total Synthesis of Lactimidomycin,"A concise synthesis of an intermediate of lactimidomycin, a glutarimide-containing macrocyclic polyketide produced by an actinomycete, has been accomplished in 35% overall yield from a known vinylketene silyl N,O-acetal by a 10-step sequence that involves two types of asymmetric aldol reactions to install all the stereocenters, the Stille coupling to set up the whole carbon famework, and the Yamaguchi lactonization to construct the 12-membered macrolactone ring.",10.1021/ol401214f,2013-06-03,0.6183615348948767
European Journal of Organic Chemistry,Convergent Synthesis of Pancratistatin from Piperonal and Xylose,"Abstract A synthesis of the antitumour agent pancratistatin is described from piperonal and D ‐xylose. Piperonal is converted into cinnamyl bromide 11 while methyl 5‐iodoribofuranoside 12 is derived from xylose. The allylic bromide and the iodocarbohydrate are combined in a zinc‐mediated tandem reaction to afford a highly functionalised 1,7‐diene, which is then converted into the corresponding cyclohexene by ring‐closing olefin metathesis. Subsequent Overman rearrangement, dihydroxylation and deprotection afford the natural product in a total of 25 steps from the two starting materials. The longest linear sequence is from piperonal and gives rise to pancratistatin in 18 steps and 7.0 % overall yield. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2009)",10.1002/ejoc.200900719,2009-08-06,0.6183602982498654
Journal of the American Chemical Society,Total Synthesis of (+)-Calyculin A and (−)-Calyculin B:  Asymmetric Synthesis of the C(9−25) Spiroketal Dipropionate Subunit,"An asymmetric synthesis of the stereochemically fully endowed C(9−25) spiroketal fragment (+)- BC of the calyculins ( 1 − 8 ) is described. Highlights of the synthesis include: a highly diastereoselective IBr-induced iodocarbonate cyclization to introduce the C(21) stereocenter in epoxide (+)- 18, fragment unions exploiting the reaction of acyl anion equivalents with epoxides to construct masked advanced aldols (−)- 35 and (+)- 71 as single diastereomers, chelation-controlled addition of the C(14−15) vinyl group to aldehyde (+)- 38 to set the stereogenicity at C(16), selective reduction of the C(13) ketone via 1,3-induction, and development of an orthogonal protection scheme permitting both convenient installation of the C(17) phosphate group and flexibility in subsequent fragment couplings.",10.1021/ja992134m,1999-10-30,0.6183331492009821
Synlett,Concise Total Synthesis of (+)-Atlanticone C,"The first enantioselective total synthesis of (+)-atlanticone C is described. The complex tricyclic protoilludane core was rapidly assembled by a photochemical reaction cascade starting from an easily accessible indanone precursor (3 steps). Optimization of an enantioselective Corey–Bakshi–Shibata reduction permitted a catalytic chiral reso­lution of the racemic photoproduct (45% over two steps; up to 98% ee). The enantiomerically enriched photoproduct was efficiently transformed into the (+)-enantiomer of atlanticone C (10 steps; 18% yield), and the absolute configuration of naturally occurring (–)-atlanticone C was thereby determined.",10.1055/s-0040-1707215,2020-07-31,0.6183228360172587
European Journal of Organic Chemistry,"Synthesis of (+)‐Epoxydon, (–)‐Phyllostine, (–)‐RKTS 33, and (–)‐Parasitenone Featuring Selective Sulfonylation and Oxirane Ring Closure of Aldol Cyclization Products","Two new synthetic approaches to anhydrogabosines are developed from the polyoxygenated aldol cyclization intermediates, bearing different O‐protecting groups, which were transformed to various gabosine‐type cyclitols. Selective sulfonylation on the required hydroxyl group of the intermediates and the subsequent oxirane ring closure are employed as the key steps in both approaches, by which (+)‐epoxydon, (–)‐phyllostine, (–)‐RKTS 33, and (–)‐parasitenone were synthesized from δ‐ d ‐gluconolactone.",10.1002/ejoc.202000486,2020-06-05,0.6183186814624886
European Journal of Organic Chemistry,A New Approach to Erythrinanes through Pummerer-Type Cyclization,"A successful new strategy for the synthesis of erythrinanes is reported. (Nitromethyl)arene derivative 16 was condensed with aldehyde 17 to give nitro aldol 19. After removal of the hydroxy group, the subunits 26a,b, containing the erythrinane rings A and D, were formed by intramolecular Michael addition. Reduction of the nitro function, followed by cyclization of the resulting amino group with the appended acetate group afforded the bicyclic lactams 29a,b, bearing an angular aryl group. Two-carbon elongation at the nitrogen atoms of 29a and 29b by means of hetero Michael addition of methyl phenyl sulfoxide, followed by Pummerer-type cyclization, gave cis- and trans-11-phenylthioerythrinan-8-ones 35a and 35b, respectively. Reductive desulfurization at C-11 furnished the desired erythrinan-8-ones 39a and 39b in 8 steps from 16.",10.1002/(sici)1099-0690(199904)1999:4<909::aid-ejoc909>3.0.co;2-7,1999-04-01,0.6183170058753201
Angewandte Chemie International Edition,Total Synthesis of (−)‐Samaderine Y from (<i>S</i>)‐(+)‐Carvone,"Elegant, efficient, and enantiospecific describe the first total synthesis of the quassinoid (−)-samaderine Y (see scheme), which has been shown to display in vitro cytotoxicity and is of interest as a potential antitumor agent. Its synthesis has been accomplished from (S)-(+)-carvone in 21 steps.",10.1002/anie.200502763,2005-11-16,0.6183161989035355
Journal of the American Chemical Society,"A General and Enantioselective Approach to Pentoses: A Rapid Synthesis of PSI-6130, the Nucleoside Core of Sofosbuvir","An efficient route towards biologically relevant pentose derivatives is described. The de novo synthetic strategy features an enantioselective α-oxidation reaction enabled by a chiral amine in conjunction with copper(II) catalysis. A subsequent Mukaiyama aldol coupling allows for the incorporation of a wide array of modular two-carbon fragments. Lactone intermediates accessed via this route provide a useful platform for elaboration, as demonstrated by the preparation of a variety of C-nucleosides and fluorinated pentoses. Finally, this work has facilitated expedient syntheses of pharmaceutically active compounds currently in clinical use.",10.1021/ja502205q,2014-03-26,0.6183134555572429
Journal of Organic Chemistry,"<b>An Improved Synthesis of 7-Substituted </b><b>Pyrrolo[3,2-</b><b><i>d</i></b><b>]pyrimidines</b>","Base (NaOMe)-catalyzed condensation of 3,3-dimethoxypropionitrile with aldehydes followed by hydrolysis with 6 N HCl gives the unsaturated cyano aldehydes 5. Catalytic reduction of the double bond followed by reaction with diethyl aminomalonate affords the enamines 7, which cyclize to the aminopyrroles 2 on treatment with NaOMe. While the amino group in 2 is unreactive toward many guanylating reagents, acid (AcOH)-catalyzed guanylation occurs easily with 10 to give 12 along with methyl mercaptan as a byproduct. Subsequent facile removal of the carbamate groups and ring closure to the pyrrolo[3,2-d]pyrimidine ring system occurs on treatment with base. The use of HgCl(2) in place of AcOH ties up the mercaptan and eliminates the odor problem. For larger scale reactions where the mercaptan odor and the use of Hg salts are undesirable, the use of the methoxy analogue 11 is preferred. Using this procedure, benzaldehyde has been converted to the 7-(phenylmethyl)pyrrolo[3,2-d]pyrimidine (1a), a potent inhibitor of the enzyme purine nucleoside phosphorylase, in 31% overall yield with only three isolation steps.",10.1021/jo971062j,1997-11-01,0.6183129073709388
Organic Letters,Total Synthesis of (+)-Lepadin F,"An enantioselective total synthesis of (+)-lepadin F is described. The synthetic sequence features an intermolecular aza-[3 + 3] annulation, homologation of a vinylogous amide via Eschenmoser's episulfide contraction, and a highly stereoselective hydrogenation essential for achieving the 1,3-anti relative stereochemistry at C2 and C8a.",10.1021/ol802068q,2008-09-27,0.6182988703916236
Tetrahedron,An improved cyclization protocol for the synthesis of diazabicyclo[4.3.0]alkanes,,10.1016/j.tetlet.2005.04.082,2005-05-11,0.6182937767008739
Synthesis,"Synthesis of (1’S,3’R)-3-(3’-Amino-2’,2’-dimethylcyclobutyl)propan-1-ol from (-)-β-Pinene","All articles of this category The title compound 3 , a useful intermediate in the synthesis of carbocyclic analogs of nucleosides was synthesized from (-)- β -pinene (4) in seven steps: oxidation of 4 to (+)-nopinone (5) ; Beckmann rearrangement of the oxime- O -sulfonic acid of 5 to the bicyclic lactam 7 (a two-step procedure via oxime 6 is also described); hydrolytic ring opening of 7 to form amino acid • HCl 8 ; and reduction of the corresponding protected methyl ester 10 followed by deprotection. Overall yield, 67% from lactam 7 . (-)- β -pinene - (+)-nopinone - Beckmann rearrangement - hydroxylamine- O -sulfonic acid - carbocyclic nucleosides",10.1055/s-1996-4191,1996-02-01,0.6182915902466382
Organic Process Research & Development,Development of a Scalable and Sublimation-Free Route to MTAD,"The cyclic azodicarbonyl 4-methyl-1,2,4-triazoline-3,5-dione (MTAD) is a versatile and powerful reagent used mainly in cycloaddition chemistry. Though known for more than 50 years, its unsafe preparation, as well as purification by sublimation, hampered its widespread applicability on a larger scale. Herein we report a scalable and safe route to MTAD, which avoids the generation of methyl isocyanate. Moreover, we demonstrate that sublimation can be circumvented by the application of judicious oxidation conditions, followed by simple filtration. Overall, up to 25 g of MTAD was prepared in a single batch from commercial starting materials in three steps, with recrystallization serving as the only purification in the sequence. When employed in dearomative methodologies, the MTAD obtained by this protocol displayed synthetic efficiency equivalent to that of MTAD purified by sublimation.",10.1021/acs.oprd.0c00470,2020-12-04,0.6182871024035438
Organic Process Research & Development,Decagram-Scale Synthesis of the Novel Bacterial Topoisomerase Inhibitor OSUAB-0284,"Medicinal chemistry efforts identified OSUAB-0284 ( 2 ) as a preclinical candidate to treat staphylococcal infections, especially those caused by methicillin-resistant Staphylococcus aureus (MRSA). Herein, we describe a fit-for-purpose route that enabled the production of >20 g of API for toxicology studies and further preclinical characterization. Process improvements include a 16-fold increase in yield over the longest sequence, a 21-fold increase in efficiency for the cost-limiting reagent, and reduction of chromatography to one silica plug across an 18-step route.",10.1021/acs.oprd.5c00033,2025-03-26,0.6182754256448336
Synthesis,Synthesis of a New Phorbazole and Its Derivatives,"Abstract Phorbazoles are chlorinated marine alkaloids containing pyrrole, oxazole and phenol ring units, and differ in the number and positions of chlorine atoms. They are isolated from sea sponges and nudibranchs. In this work, a convenient synthetic method leading to a new phorbazole and its derivatives is developed. This synthesis of synthetic phorbazole G and its derivatives is achieved in seven steps in good overall yields of 26–52%. It involves formation of the pyrrole-oxazole skeleton followed by chlorination. The pyrrole-oxazole skeleton is synthesized from pyrrole and substituted acetophenones, and the key step involves cyclodehydration of amide intermediates to give protected oxazoles, followed by hydrolysis.",10.1055/a-1655-6078,2021-09-27,0.6182689153779738
Organic Letters,Total Synthesis of Gombamide A,"The first total synthesis of Gombamide A (1), a cytotoxic cyclic thiopeptide from the sponge Clathria gombawuiensis, has been achieved. Highlights of the convergent synthesis feature a disulfide bond forming cascade to close the 17-membered macrocycle and a selenoazidylation procedure to access the unusual para-hydroxystyrlyamide (pHSA) moiety. The synthesis required 18 steps, 11 steps in its longest linear sequence, and proceeded in 9.1% overall yield. This work will facilitate the study of the biological effects of Gombamide A and provide groundwork to explore the structure-activity relationship around this rare natural product.",10.1021/acs.orglett.6b01825,2016-07-21,0.6182678805118076
Organic Letters,Total Synthesis of the Immunosuppressants Myriocin and 2-<i>epi</i>-Myriocin,Total syntheses of the natural immunosuppressant myriocin (1) and the equipotent unnatural analogue 2-epi-myriocin (in protected form) have been achieved through a common strategy. The key transformations are the efficient synthesis of a quaternary (E)-vinylglycine by asymmetric deconjugative alkylation of a dehydroamino acid and an unusually highly diastereoselective dihydroxylation of the vinylglycine alkene.,10.1021/ol801709c,2008-08-23,0.6182397449569565
Tetrahedron,"Methods for indole alkaloid synthesis. A highly convergent strategy for the synthesis of a 3-methyl-6,7-dehydroaspidospermidine system.",,10.1016/s0040-4039(00)98352-7,1985-01-01,0.6182388859462342
Synlett,Stereoselective Synthesis of Macrosphelide I,"An efficient total synthesis of macrosphelide I, has been achieved starting from commercially available chiral materials, ethyl ( S )-lactate and methyl ( R )-3-hydroxybutyrate. Titanium(IV) promoted the regioselective nucleophilic opening reaction of epoxy alcohol with benzoic acid, Sharpless epoxidation, ring-closing metathesis and Yamaguchi esterification as key steps for the construction of the 16-membered macrotriolide.",10.1055/s-0033-1338657,2014-07-16,0.6182272289906545
Journal of the American Chemical Society,"A Practical Entry to the Crambescidin Family of Guanidine Alkaloids. Enantioselective Total Syntheses of Ptilomycalin A, Crambescidin 657 and Its Methyl Ester (Neofolitispates 2), and Crambescidin 800","Among the most structurally remarkable guanidine natural products are the crambescidin/ptilomycalin A family of marine alkaloids. The evolution of a practical strategy for preparing pharmacologically significant crambescidin/ptilomycalin A alkaloids that lack oxidation at C13 is described. The first total syntheses of crambescidin 800 ( 2 ), crambescidin 657 ( 6 ), and neofolitispate 2 ( 7 ) are reported in full detail. The central strategic step in these convergent total syntheses is tethered Biginelli condensation of β-keto ester 24 with ureido aminal 61 to combine all carbons of the guanidine nucleus and set the pivotal C10−C13 stereorelationship. The total synthesis of crambescidin 800 ( 2 ) was accomplished in 3% overall yield from commercially available 3-butyn-1-ol by way of 16 isolated and purified intermediates. Full details of our earlier total synthesis of ptilomycalin A ( 1 ) are also presented. The total syntheses described in this disclosure confirm the stereochemical assignments of 1, 2, 6, and 7 and rigorously establish that the absolute configuration of the hydroxyspermidine side chain of crambescidin 800 ( 2 ) is S .",10.1021/ja000234i,2000-05-01,0.6182237727222216
Organic Letters,Synthesis of (−)-Agelastatin A by [3.3] Sigmatropic Rearrangement of Allyl Cyanate,Total synthesis of (-)-agelastatin A has been achieved starting from l-arabitol. The highlights in our synthesis include the preparation of vicinal diamine moiety by [3.3] sigmatropic rearrangement of allyl cyanate and construction of central ring-C with ring-closing metathesis.,10.1021/ol0709735,2007-06-30,0.6182142254178307
Angewandte Chemie International Edition,Total Syntheses of (−)‐Huperzine Q and (+)‐Lycopladines B and C,"Utilizing a late-stage enamine bromofunctionalization strategy, the twelve-step total synthesis of (-)-huperzine Q was accomplished. Furthermore, the first total syntheses of (+)-lycopladines B and C are described. An unprecedented X-ray crystal structure of an unusual epoxyamine intermediate is also reported, and the synthetic application of this intermediate in natural product synthesis is demonstrated.",10.1002/anie.201409503,2014-10-30,0.6182116323223212
Synthesis,"A Novel Methodology for the Asymmetric Synthesis of 2,3,5-Trisubstituted Piperazine Derivatives","Abstract Piperazines constitute an important structural feature of many pharmaceuticals. For the discovery of new drugs, the ability to modify the lead compound’s structure is crucial. Herein, we provide an efficient method for the synthesis of chiral 2,3,5-trisubstituted piperazine structures. Our route enables the synthesis of several novel chiral aryl aziridinyl ketones that could be converted into aziridine-fused bicyclic imines. The reduction of these imines and the nucleophilic ring-opening reaction of the aziridine ring allowed us to synthesize highly functionalized piperazine derivatives.",10.1055/s-0040-1720114,2024-04-10,0.6181714132132031
Journal of the American Chemical Society,Asymmetric Synthesis of Gonytolide A: Strategic Use of an Aryl Halide Blocking Group for Oxidative Coupling,"The first synthesis of the chromanone lactone dimer gonytolide A has been achieved employing vanadium(V)-mediated oxidative coupling of the monomer gonytolide C. An o-bromine blocking group strategy was employed to favor para- para coupling and to enable kinetic resolution of (±)-gonytolide C. Asymmetric conjugate reduction enabled practical kinetic resolution of a chiral, racemic precursor and the asymmetric synthesis of (+)-gonytolide A and its atropisomer.",10.1021/jacs.8b02535,2018-04-16,0.6181647457951004
Organic Letters,Synthesis of the Tetracyclic ABCD Ring Domain of Calyciphylline A-Type Alkaloids via Reductive Radical Cyclizations,A tetracyclic compound with the ABCD ring framework of calyciphylline A-type alkaloids was synthesized from a cis-3a-methyloctahydroindole triggered by a 5-endo radical cyclization. The synthesis required two additional ring-forming steps: the construction of a seven-membered ring by aldol cyclization and the azabicyclic fragment by a radical ring closure of a trichloroacetamide-tethered enol acetate followed by a diastereoselective α-methylation of the lactam group.,10.1021/acs.orglett.7b00035,2017-02-09,0.6181556981951656
Organic Process Research & Development,"Synthetic Process Development of ( <i>R</i> )-(+)-1,2-Epoxy-5-hexene: An Important Chiral Building Block","High Resolution Image Download MS PowerPoint Slide Herein, we describe two practical approaches to synthesize ( R )-(+)-1,2-epoxy-5-hexene from inexpensive and readily available raw materials and reagents. The first approach is a two-step sequence, involving an epoxidation with meta -chloroperoxybenzoic acid (mCPBA) and a chiral resolution with (salen)Co(II), producing ( R )-(+)-1,2-epoxy-5-hexene in 24–30% overall yield. The second approach utilizes readily available ( R )-epichlorohydrin as the starting material and features an epoxide ring-opening reaction with allylMgCl and the NaOH-mediated ring closure reaction. Development of this two-step process affords R -(+)-1,2-epoxy-5-hexene in overall isolated yields of 55–60% with an exceptional purity profile. Both approaches have been successfully demonstrated on 100–200 g scales.",10.1021/acs.oprd.4c00101,2024-08-01,0.6181434478918504
Tetrahedron,A new route for the synthesis of indolizidine (−)-209D: excellent diastereoselectivity in the intramolecular hydroamination of alkynes,,10.1016/j.tetlet.2005.01.139,2005-02-11,0.6181342873935914
Tetrahedron,A new approach to isoindolobenzazepines via a ring-expansion of isoindoloisoquinoline: Synthesis of lennoxamine and chilenine,,10.1016/s0040-4039(99)00140-9,1999-03-01,0.6181332967927148
Organic Letters,Enantioselective Total Synthesis of Litseaverticillols A and B,"[reaction: see text] The first enantioselective total synthesis of the (1R,5S)-stereoisomer of litseaverticillols A and B, anti-HIV monocyclic sesquiterpenoids isolated from a perennial shrub found in Vietnam, was accomplished in six steps from homogeranic acid by employing the Evans asymmetric aldol reaction and a microwave-promoted cyclization of a stannylated thiol ester intermediate as the C-C bond-forming steps.",10.1021/ol053122a,2006-03-21,0.6181331983421174
Journal of Organic Chemistry,"Total Synthesis of Malyngamides K, L, and 5′′-<i>epi</i>-C and Absolute Configuration of Malyngamide L","An accelerated, enantioselective, and general synthetic route to a class of malyngamides, K (1), L (3), and 5''-epi-C (4), bearing a cyclohexenone ring or a heavily oxygenated six-membered ring and a vinyl chloride structural motif was developed. The key step was the Suzuki cross-coupling reaction of boronic acids 6-8 with unsaturated carboxylic amides 5a,b possessing the chlorovinyl iodide functionality for the construction of the skeletons of 1-4. The key intermediates 10a,b were prepared using Ogilvie's method for the construction of the chlorovinyl iodide functionality. The NMR data of the synthetic compound 2 were in full agreement with those of the reported product, and the discrepancy in the specific rotation data suggested that the correct structure of malyngamide L should be 3, in which the absolute configuration of the amine part was enantiomeric to that in compound 2. Then the absolute configuration of the stereogenic center at C(3'') and C(4'') in malyngamide L was confirmed by synthesis of compound 3.",10.1021/jo2003852,2011-04-15,0.6181326048190602
European Journal of Organic Chemistry,The synthesis of 9‐<i>O</i>‐Methylpaepalantine and Dehydroxanthomegnin: Related Isocoumarin‐Containing Natural Products,"The first synthesis of two related isocoumarin‐containing natural products, 9‐ O ‐methylpaepalantine and dehydroxanthomegnin is described. Commencing with 2,4‐dimethoxybenzaldehyde and utilizing the Stobbe reaction as a key step resulted in the formation of the required naphthalene containing compound, ethyl 4‐acetoxy‐3‐allyl‐6,8‐dimethoxynaphthalene‐2‐carboxylate. O ‐Allylation of 4‐hydroxy‐6,8‐dimethoxynaphthalene‐2‐carboxylate followed by a Claisen rearrangement afforded the naphthol, ethyl 3‐allyl‐4‐hydroxy‐6,8‐dimethoxynaphthalene‐2‐carboxylate. Introduction of a methoxy substituent onto the 1‐position of the naphthalene nucleus utilizing a PIFA‐mediated method afforded, after O ‐methylation, ethyl 3‐allyl‐1,4,6,8‐tetramethoxynaphthalene‐2‐carboxylate. Reduction of the ester was followed by oxidation to the aromatic acid, utilizing firstly a PCC oxidation and then a Pinnick oxidation to afford 3‐allyl‐1,4,6,8‐tetramethoxynaphthalene‐2‐carboxylic acid. Wacker oxidation of the aromatic acid resulted in the formation of 5,7,9,10‐tetramethoxy‐3‐methyl‐1 H ‐benzo[ g ]isochromen‐1‐one, which was then converted into 9‐ O ‐methylpaepalantine by treatment with boron trichloride. Utilizing similar synthetic methodology dehydroxanthomegnin was synthesized in thirteen steps commencing from 2,4,5‐trimethoxybenzaldehyde in an overall yield of 1.3 %.",10.1002/ejoc.201801595,2019-01-02,0.6181258892075183
Tetrahedron,TiCl4 Mediated LiBH4 reduction of β-ketophosphine oxides: a high stereoselective route to the synthesis of anti-β-hydroxyphosphine oxides,,10.1016/0040-4039(96)01601-2,1996-10-01,0.618120091070626
Tetrahedron,"Total Synthesis of Nagstatin, an N-Acetyl-β-?-glucosaminidase Inhibitor",,10.1016/0040-4039(95)01361-k,1995-01-16,0.6181055445346838
Tetrahedron,"Total synthesis of nagstatin, an N-acetyl-β-D-glucosaminidase inhibitor",,10.1016/00404-0399(50)1361-k,1995-09-01,0.6181055445346838
Tetrahedron,"Total Synthesis of Nagstatin, an N-Acetyl-β-?-glucosaminidase Inhibitor",,10.1016/00404-0399(50)1361k-,1995-09-11,0.6181055445346838
Tetrahedron,"Synthesis of (5) ()-6-[(1-methyl-1,2,3-triazol-4-yl)methylene]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid, a novel carbapenem derivative, from 6-aminopenicillanic acid",,10.1016/s0040-4039(00)99417-6,1989-01-01,0.6180985509581338
Angewandte Chemie International Edition,"Total Synthesis of the C‐1027 Chromophore Core: Extremely Facile Enediyne Formation through SmI<sub>2</sub>‐Mediated 1,2‐Elimination","The spontaneous aromatization of the enediyne chromophore of the potent antitumor agent C-1027 generates a p-benzyne biradical, which cleaves double-stranded DNA. The title reaction was developed for the construction of nine-membered-ring enediynes and applied as the final step in the synthesis of the exceptionally unstable core structure of the C-1027 chromophore (see scheme; Boc, MOM, MPM, and TES are protecting groups; Ms=methanesulfonyl).",10.1002/anie.200704842,2008-01-21,0.6180975322582141
Tetrahedron,An efficient total synthesis of a new and highly active analog of lactacystin,,10.1016/s0040-4039(98)01674-8,1998-10-01,0.6180975254938612
Tetrahedron,Synthesis of chiral non-racemic 2-arylpyrrolines by a [3+2] cycloaddition route,,10.1016/0040-4039(96)01176-8,1996-08-01,0.6180965861435563
Tetrahedron,Preparation of tagged glucose as a key intermediate in the synthesis of branched oligosaccharides,,10.1016/j.tetlet.2011.01.149,2011-02-07,0.6180855481180804
Synlett,Synthetic Study of the Angular Tetracyclic Core Skeleton of Landmycine A via Masamune-Bergman Cyclization,"We describe the synthesis, via Masamune–Bergman cyclization, of an angucycline derivative involving a quinone in the B ring and a nonaromatic hydroxylated C ring. The naphthoquinone was synthesized via the copper-catalyzed Ullmann reaction of the dihalo aryl moiety, and the subsequent oxidation of a corresponding hydroquinone. The aryl dihalide was prepared by the dihalogenation of the 1,4-diradical generated during the Masamune–Bergman cyclization of the 1,2- dialkynylbenzene under neutral conditions. This methodology suggests a new route for the construction of natural products containing an anthraquinone skeleton.",10.1055/s-0031-1290937,2012-05-14,0.6180810418267596
Tetrahedron,"Conformationally locked nucleosides. Synthesis of 3(R,S)-(adenin-9-yl)-1- and 3(R,S)-(cytosin-1-yl)-1-hydroxymethylbicyclo[2,1,1]hexanes",,10.1016/s0040-4039(00)01246-6,2000-09-01,0.6180737105499612
Organic Letters,Application of Vinamidinium Salt Chemistry for a Palladium Free Synthesis of Anti-Malarial MMV048: A “Bottom-Up” Approach,") is a clinical compound under investigation for antimalarial activity. A new synthetic route was developed which couples two aromatic fragments while forming the central pyridine ring over two steps. This sequence takes advantage of raw materials used in the existing etoricoxib supply chain and eliminates the need for palladium catalysts, which were projected to be major cost-drivers.",10.1021/acs.orglett.1c01725,2021-06-29,0.6180632261523712
Angewandte Chemie International Edition,A Concise Route to the Strongylophorines,An efficient eight-step semisynthesis of strongylophorine-2 from the abundant building block isocupressic acid is reported. The route represents the first synthetic entry into this class of natural products and provides access to six additional family members. A novel iron(III)-mediated rearrangement-cyclization cascade and a directed photochemical sp(3) C-H δ-lactonization are the key transformations that enable concise assembly of these bioactive polycyclic meroterpenoids.,10.1002/anie.201602476,2016-05-30,0.6180363238320193
Tetrahedron,A carbonylative cross-coupling strategy to the total synthesis of the sarcodictyins: preliminary studies and synthesis of a cyclization precursor,,10.1016/s0040-4039(01)01608-2,2001-10-01,0.6180297281298538
European Journal of Organic Chemistry,Enantioselective Synthesis of Antifungal Agent Voriconazole via Asymmetric Epoxidation of Tetrasubstituted (<i>Z</i>)‐Alkene,"Abstract A concise asymmetric synthesis of triazole antifungal agent voriconazole is described. Salient features of this synthesis include a LiOH‐controlled highly stereospecific formation of ( Z )‐enol triflate from 2‐difluorobenzene acetoacetate to access the crucial tetrasubstituted ( Z )‐allylic alcohol, and a highly enantioselective VO(O i Pr) 3 /BHA ligand‐catalyzed epoxidation to construct the critical contiguous carbon stereocenters in a single step.",10.1002/ejoc.202400400,2024-06-14,0.6180118408834202
Tetrahedron,Formal synthesis of (±)-camptothecin via tricyclic lactone as key synthon,,10.1016/j.tetlet.2010.04.019,2010-04-13,0.6180007631209199
Organic Letters,Convergent Stereoselective Synthesis of the C16–C37 Subunit of Sorangicin A,"A convergent stereoselective route to the C16–C37 fragment of sorangicin A is disclosed using an α-chloro sulfide for C–C bond formation. The key intermediate, an α,β-unsaturated ketone, is revealed by a [2,3] sigmatropic rearrangement of a propargylic sulfoxide. Three disparate approaches are detailed to create the C25 carbinol stereocenter. The cis -2,6-disubstitution of the THP ring is secured by ionic hydrogenation. A cross-metathesis reaction and Julia–Kocienski olefination furnish the C16–C37 fragment of sorangicin A.",10.1021/acs.orglett.9b02729,2019-09-25,0.6179951869075554
Tetrahedron,Probing the formation and chemistry of enoxyoxirane derivatives in the C-ring en route to guanacastepene,,10.1016/j.tetlet.2004.02.162,2004-04-03,0.6179842520818374
Tetrahedron,An efficient asymmetric synthesis of 11-deoxyanthracyclinone,,10.1016/s0040-4039(00)99232-3,1989-01-01,0.6179801559152234
Journal of the American Chemical Society,Catalytic Enantioselective Synthesis of Chiral Phthalides by SmI<sub>2</sub>-Mediated Reductive Cyclization of 2-Acylarylcarboxylates,"A significant new and efficient catalytic asymmetric approach for the highly enantioselective synthesis of chiral phthalides by SmI2-induced reductive cyclization of 2-acylarylcarbonylates was developed. The combination of (4S,5R)-4,5-diphenyloxazolidin-2-one and 2,2,6,6-tetramethylpiperidine was found to be a very effective catalyst system in the reaction. This method provides a ready access to a broad range of enantiomerically enriched phthalides (up to 99% ee).",10.1021/ja061114z,2006-04-08,0.6179794482729785
Journal of Organic Chemistry,Enantioselective Synthesis of Protected Nitrocyclohexitols with Five Stereocenters. Total Synthesis of (+)-Pancratistatin,"2-Methoxymethylpyrrolidine best performed, among several other proline derivatives, to control the enantioselective [3+3] annulation of β-(hetero)aryl-α-nitro-α,β-enals with commercial 2,2-dimethyl-1,3-dioxan-5-one, a procedure that renders highly oxygenated nitrocyclohexanes endowed with five new stereocenters. Use of this reaction allowed the development of a total synthesis of the antitumoral natural product (+)-pancratistatin; it also converted our previous racemic route to tetrodotoxin into an enantioselective one.",10.1021/jo3022567,2012-11-26,0.6179693533843658
Journal of the American Chemical Society,Atroposelective Total Synthesis of Darobactin A,"A concise, modular synthesis of the novel antibiotic darobactin A is disclosed. The synthesis successfully forges the hallmark strained macrocyclic ring systems in a sequential fashion. Key transformations include two atroposelective Larock-based macrocyclizations, one of which proceeds with exquisite regioselectivity despite bearing an unprotected alkyne. The synthesis is designed with medicinal chemistry considerations in mind, appending key portions of the molecule at a late stage. Requisite unnatural amino acid building blocks are easily prepared in an enantiopure form using C-H activation and decarboxylative cross-coupling tactics.",10.1021/jacs.2c05892,2022-08-04,0.6179557186369213
Organic Letters,Total Synthesis of Hinckdentine A,"The total synthesis of (±)-hinckdentine A is described herein. A cyanide-catalyzed imino-Stetter reaction of the aldimine derived from ethyl 2-amino-3,5-dibromocinnamate and 5-bromo-2-nitrobenzaldehyde followed by oxidative rearrangement afforded a 2,2-disubstituted 3-indolinone derivative containing the carbon skeleton and all of the functional groups present in the natural product correctly positioned, including three bromine atoms. Subsequent D-ring formation and seven-membered C-ring construction completed the total synthesis of hinckdentine A.",10.1021/acs.orglett.1c00323,2021-02-25,0.6179500832071044
Journal of Organic Chemistry,A New Route to Diverse 1-Azasugars from<i>N</i>-Boc-5-hydroxy-3-piperidene as a Common Building Block,"A new general method for the synthesis of a variety of 1-azasugars with a nitrogen atom at the anomeric position is described. The readily available chiral N-Boc-5-hydroxy-3-piperidene 3 is transformed to isofagomine (2), homoisofagomine (13), and 5'-deoxyisofagomine (14) via stereoselective epoxidation and regioselective ring-cleavage in a highly stereocontrolled manner. In addition, the synthesis of all four stereoisomers of 3,4,5-trihydroxypiperidines (18-21) classified as 1-azasugar-type glycosidase inhibitors was stereoselectively achieved from the (chiral) piperidene 3.",10.1021/jo050519j,2005-05-19,0.6179374049352478
Tetrahedron,"Popolohuanone E, a topoisomerase-II inhibitor with selective lung tumor cytotoxicity from the Pohnpei sponge Dysidea sp.",,10.1016/s0040-4039(00)79211-2,1993-06-01,0.617927713236992
Organic Letters,A Modular Approach to Trisubstituted Chiral Piperidines,"We report a modular strategy for the synthesis of trisubstituted chiral piperidines. First, a scalable, chiral-pool synthesis of an orthogonally protected piperidine tricarboxylic acid diester was developed. This synthesis involves a formal 4 + 2 cyclization between choro-homoserine and acetylene dicarboxylate, followed by a diastereoselective reduction, cyclic anhydride formation, and regioselective ring-opening process to give the final product as a single enantio- and diastereomer at >50 g scale. Next, we demonstrated that the piperidine tricarboxylate intermediate can undergo sequential decarboxylative functionalizations using modern transition metal-catalyzed or photocatalytic methodologies. As the result, highly elaborated chiral piperidines and pipecolic esters were prepared in a chemo- and stereoselective manner.",10.1021/acs.orglett.5c02419,2025-07-31,0.6179252427618158
Synlett,Synthesis of a C1–C12 Fragment of Gulmirecin B,"The synthesis of a C1–C14 fragment of the macrolide antibiotic gulmirecin B through formation of the C7–C8 bond by addition of a vinyllithium intermediate to a C1–C7 aldehyde was investigated. This crucial coupling was successful with a vinyllithium reagent corresponding to a C8–C12 fragment. The C8–C12 vinyl bromide was prepared from l-malic acid. The C1–C7 aldehyde building block was synthesized from hex-5-enoic acid by using an Evans alkylation, a cross-metathesis, and an asymmetric dihydroxylation as key steps.",10.1055/s-0037-1611559,2019-05-22,0.6179190404485134
Journal of the American Chemical Society,"Total Synthesis and Molecular Target of Largazole, a Histone Deacetylase Inhibitor","Full details of the concise and convergent synthesis (eight steps, 19% overall yield), its extension to the preparation of a series of key analogues, and the molecular target and pharmacophore of largazole are described. Central to the synthesis of largazole is a macrocyclization reaction for formation of the strained 16-membered depsipeptide core followed by an olefin cross-metathesis reaction for installation of the thioester. The biological evaluation of largazole and its key analogues, including an acetyl analogue, a thiol analogue, and a hydroxyl analogue, suggested that histone deacetylases (HDACs) are molecular targets of largazole and largazole is a class I HDAC inhibitor. In addition, structure-activity relationship (SAR) studies revealed that the thiol group is the pharmacophore of the natural product. Largazole's HDAC inhibitory activity correlates with its antiproliferative activity.",10.1021/ja8013727,2008-05-29,0.6178914756041476
Tetrahedron,"Enaminothiones of imidazolidine nitroxides, a new route to acetylenic compounds of 3-imidazoline",,10.1016/s0040-4039(00)84331-2,1986-01-01,0.6178889252288143
Journal of Organic Chemistry,"A General Strategy for the Synthesis of Vincamajine-Related Indole Alkaloids:  Stereocontrolled Total Synthesis of (+)-Dehydrovoachalotine, (−)-Vincamajinine, and (−)-11-Methoxy-17-epivincamajine as Well as the Related Quebrachidine Diol, Vincamajine Diol, and Vincarinol<sup>1</sup>","[structures: see text] The highly convergent stereocontrolled total synthesis of (-)-vincamajinine (7), (-)-11-methoxy-17-epivincamajine (9), and the oxygen-bridged (+)-dehydrovoachalotine (22) are described. Key steps in the synthesis of 7 and 9 involved the stereospecific enolate-driven palladium-catalyzed cross-coupling reaction, a Tollens reaction, an acid-assisted intramolecular cyclization to form the C(7)-C(17) quaternary center, and two stereospecific reductions. The efficiency of this strategy is illustrated by the completion of the synthesis of 7 and 9 in 16 [from d-(+)-tryptophan methyl ester 17] and 17 (from the Schöllkopf chiral auxiliary 27) reaction vessels, respectively. This constitutes the first total synthesis of these indole alkaloids and provides the first regiospecific route to 11-methoxy-substituted ajmaline/vincamajine-related alkaloids. The synthesis of 22 required a novel DDQ-mediated cyclization to furnish the C(6)-O(17) bond, executed in stereospecific fashion. Completion of these syntheses illustrates a concise and versatile strategy for the synthesis of vincamajine-related alkaloids, which has also been employed to prepare the related compounds quebrachidine diol (53), vincamajine diol (56), and vincarinol (59).",10.1021/jo040282b,2005-04-19,0.6178888851728074
Organic Letters,Bioinspired Total Synthesis of Bussealin E,"The first total synthesis of bussealin E, a natural product with a unique cycloheptadibenzofuran scaffold, is reported. A strategy inspired by a proposed biosynthesis was employed whereby a diphenylpropane derivative underwent an oxidative phenolic coupling to forge the tetracyclic ring system. The synthesis of the diphenylpropane featured a key sp 2 –sp 3 Hiyama coupling between a vinyldisiloxane and a benzylic bromide.",10.1021/acs.orglett.8b00340,2018-03-02,0.6178876359634194
Tetrahedron,"New route synthesis of indolizines via 1,3-dipolar cycloaddition of pyridiniums and alkynes",,10.1016/j.tetlet.2009.09.143,2009-09-30,0.6178876282804424
European Journal of Organic Chemistry,Sceptrin – Enantioselective Synthesis of a Tetrasubstituted all‐<i>trans</i> Cyclobutane Key Intermediate,"The asymmetric synthesis of both enantiomers of tetrasubstituted all‐ trans dimethyl 3,4‐diacetylcyclobutane‐1,2‐dicarboxylate with high enantiomeric purity (&gt;98 % ee ) using a valine‐derived chiral auxiliary in a diastereoselective photodimerization is reported. The absolute configuration was assigned by single‐crystal X‐ray diffraction analysis. Because this cyclobutane is a key intermediate in the total synthesis of (–)‐sceptrin and ageliferin, our findings strengthen the recently revised absolute configurations of these pyrrole‐imidazole alkaloids.",10.1002/ejoc.201700882,2017-07-05,0.6178755048102657
Organic Process Research & Development,"Identification of a Manufacturing Route of Novel CRF-1 Antagonists Containing a 2,3-Dihydro-1<i>H</i>-pyrrolo[2,3-<i>b</i>]pyridine Moiety","A case study on the synthesis of novel CRF-1 antagonists containing the 2,3-dihydro-1 H -pyrrolo[2,3- b ]pyridine moiety is presented. The development of ever more efficient synthetic routes allowed the progression of three candidates at the same time. A manufacturing route was identified and successfully demonstrated on a pilot-plant scale to prepare 100 kg of the CRF-1 antagonist GW876008.",10.1021/op100147h,2010-06-28,0.6178736775236541
Journal of Organic Chemistry,Concise Synthesis of the Isothiourea Organocatalysts Homobenzotetramisole and Derivatives,"A concise approach to the synthesis of homobenzotetramisole and derivatives is described. Our strategy features a one-pot acylation-cyclization of 2-aminobenzothiazole with α,β-unsaturated acid chlorides to afford annulated pyrimidones. Subsequent Grignard addition followed by acid-promoted dehydration and reduction provides good overall yields of the title compounds in three steps and in quantities up to 10 g. The synthesis employs low-cost and readily available starting materials and enables access to both optical antipodes of these increasingly useful nucleophilic catalysts following chiral separation.",10.1021/jo400603n,2013-05-20,0.617871171432214
Organic Letters,A Highly Convergent and Efficient Synthesis of a Macrocyclic Hepatitis C Virus Protease Inhibitor BI 201302,"A highly convergent large scale synthesis of a 15-membered macrocyclic hepatitis C virus (HCV) protease inhibitor BI 201302 was achieved, in which the key features are the practical macrocyclization by Ru-catalyzed ring-closing metathesis (0.1 mol % Grela catalyst, 0.1-0.2 M concentration) and the efficient sulfone-mediated SNAr reaction.",10.1021/ol303498m,2013-02-13,0.6178673658553969
European Journal of Organic Chemistry,Synthesis of the BCD‐Ring Substructure of Granaticin A,Abstract The BCD‐ring substructure of granaticin A was synthesised following a new approach for the construction of the naphthoquinone moiety. The 2‐oxabicyclo[2.2.2]oct‐5‐ene substructure was accessible stereoselectively using a Sharpless asymmetric dihydroxylation and a diastereoselective ketone reduction in combination with Yoshii's route. The naphthoquinone B‐ring was prepared by addition of an aryllithium intermediate to an anhydride followed by a Friedel–Crafts cyclisation mediated by AlCl 3 and Mg(OTf) 2 . The success of the Friedel–Crafts cyclisation relied on the conversion of the ketone‐carboxylic acid into a lactone acetal.,10.1002/ejoc.201201104,2012-10-19,0.6178622717301406
Synthesis,"A Multikilogram-Scale Synthesis of (R)-Methyl 2-[(1r,4R)-4-(tert-Butoxycarbonylamino)cyclohexyl]-2-(2-nitrophenylsulfonamido)acetate - A Doubly Protected Building Block with Three Points of Variation","A robust and scalable synthesis of (R)-methyl 2-[(1r,4R)-4-(tert- butoxycarbonylamino)cyclohexyl]-2-(2-nitrophenylsulfon-amido)acetate is reported. This serves as a scaffold for the preparation of trans-substituted aminocyclohexanes. The key synthetic step is the reduction of d-4-hydroxyphenylglycine, or a protected equivalent, to achieve the required regiochemistry across the cyclohexyl ring.",10.1055/s-0031-1289724,2012-02-27,0.6178621729681649
Organic Letters,Pericyclic Reaction of a Zwitterionic Salt of an Enedione-diazoester. A Novel Strategy for the Synthesis of Highly Functionalized Resorcinols,Enedione-diazoesters formed from 3-TBSO-2-diazo-3-butenoates undergo base-catalyzed pericyclization that with dinitrogen extrusion and methyl migration provide a novel and efficient route to 2-carboalkoxyresorcinols. Intercepting the intermediate enolate anion with methyl vinyl ketone leads to the corresponding 4-substituted 2-carboalkoxyresorcinol and suggests generalization of this methodology.,10.1021/ol101744h,2010-09-01,0.6178526265990167
European Journal of Organic Chemistry,Synthesis of Spirocyclopropanated Analogues of Iprodione,"Abstract Methyl 1‐( tert ‐butoxycarbonylamino)cyclopropanecarboxylate ( 9 ) was converted into the spirocyclopropanated five‐membered ring analogue 7a of Iprodione ( 1 ) in five steps with an overall yield of 28 %. The spirocyclopropanated five‐membered ring analogue 8a was prepared from tert ‐butyl N ‐[1‐(hydroxymethyl)cyclopropyl]carbamate ( 10 ) in five steps with an overall yield of 19 %. En route to the spirocyclopropanated six‐membered ring analogues of Iprodione ( 1 ), the oxalic acid diamides 5b and 6b could be obtained starting from 9 or 10 in 33 or 19 % yield, respectively. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2005)",10.1002/ejoc.200400600,2005-05-25,0.617846783010343
Organic Letters,Synthesis of (+)-Vinblastine and Its Analogues,"A synthetic route to vinblastine and its analogues with an ethynyl group, which features a stereoselective coupling of an 11-membered key intermediate with vindoline, is described. Transformations of the alkynyl moiety including a partial reduction as well as a Sonogashira coupling furnished a variety of analogues.",10.1021/ol702040y,2007-10-13,0.6178441924273999
Journal of the American Chemical Society,Total Synthesis of (+)-Sorangicin A,"The final synthetic challenges associated with (+)-sorangicin A have been overcome, thus leading to the first total synthesis of this complex macrolide antibiotic. Highlights of the highly convergent synthesis include two Julia-Kociénski olefinations to unite three advanced fragments with high E-stereoselectivity. Critical to the final-stage success was the use of a carefully defined Stille coupling and a Mukaiyama macrolactonization as well as Lewis and protic acid-promoted deprotections carefully designed to suppress E/Z isomerization and/or destruction of the delicate (Z,Z,E)-trienoate linkage.",10.1021/ja906115a,2009-08-11,0.6178432194625609
Journal of Organic Chemistry,Cp<sub>2</sub>TiCl-Promoted <i>Endo-Trig</i> Radical Cyclization to Six- and Seven-Membered Carbocycles: Synthesis of (±)-Isoclavukerin A,"A systematic study is undertaken to investigate the less explored endo-trig radical cyclization in activated olefin-appended epoxides using Cp 2 TiCl. The radical generated by the Ti(III)-promoted reductive opening of the epoxy ring promptly underwent endo-trig cyclization, giving access to differently 1,3-disubstituted six- and seven-membered carbocycles in good yields and diastereoselectivity. This protocol was successfully employed in the construction of 5,7- and 6,7-fused bicyclic frameworks entailing a de novo synthesis of (±)-isoclavukerin A belonging to tri- nor -guaiane class of sesquiterpene natural products in eight simple steps from commercially available starting materials. Besides the Ti(III)-mediated reaction serving as a key step in the synthesis, a sequential [2,3]-sigmatropic rearrangement/syn-elimination of an allyl sulfenate intermediate successfully rendered the highly constrained diene moiety in the hydroazulene core of the target molecule.",10.1021/acs.joc.3c01356,2023-08-23,0.6178344869057296
Tetrahedron,"Novel synthesis of α-nitroalkenes from nitroalkanes via halogenation of intermediate N,N-bis(silyloxy)enamines",,10.1016/j.tetlet.2005.05.113,2005-06-15,0.6178288558505785
Angewandte Chemie International Edition,Sulfone‐Mediated Total Synthesis of (±)‐Lepadiformine,"Key steps in the total synthesis of the marine alkaloid (±)-lepadiformine (1) include regioselective opening of a spirocyclic aziridine ring with a sulfone-stabilized carbanion, cyclocondensation of the N,C dianion of the resulting γ-sulfonamidosulfone with an aldehyde, and highly stereoselective alkynylation by nucleophilic substitution of an aminal. SES=2-(trimethylsilyl)ethylsulfonyl.",10.1002/anie.200604670,2007-03-02,0.6178186943982216
Journal of Organic Chemistry,Synthesis of the C1−C28 Portion of Spongistatin 1 (Altohyrtin A),"A synthetic approach was developed to the C1-C28 subunit of spongistatin 1 (altohyrtin A, 65). The key step was the coupling of the AB and CD spiroketal moieties via an anti-aldol reaction of aldehyde 62 and ethyl ketone 57. The development of a method for the construction of the AB spiroketal fragment is described and included the desymmetrization of C(2)-symmetric diketone 10 and the differentiation of the two primary alcohols of 16. Further elaboration of this advanced intermediate to the desired aldehyde 62 included an Evans' syn-aldol reaction and Tebbe olefination. The synthesis of the CD spiroketal fragment 56 involved the ketalization of a triol-dione, generated in situ by deprotection of 45, to provide a favorable ratio (6-7:1) of spiroketal isomers 46 and 47, respectively. The overall protecting group strategy, involving many selective manipulations of silyl protecting groups, was successfully developed to provide the desired C1-C28 subunit of spongistatin 1 (altohyrtin A) (65).",10.1021/jo9910987,1999-10-01,0.6178171801724419
Synthesis,An Enantioselective Synthesis of Cyclopentyl-L-Aspartic Acid Amenable to Large Scale,All articles of this category A new enantioselective synthesis of cyclopentyl-L-aspartic acid[( S )-αamino-1-(carboxy)cyclopentaneacetic acid] (1) and its N -Boc derivative 2 has been developed. This synthesis is amenable to kilogram scale preparation and avoids low temperature reactions and column chromatography. enantioselective synthesis - cyclopentyl-L-aspartic acid - Strecker synthesis - no chromatography,10.1055/s-1997-1518,1997-01-01,0.6178066422689332
Journal of Organic Chemistry,Asymmetric Total Synthesis of (+)-Crassalactone D,"The asymmetric total synthesis of (+)-crassalactone D (4), a naturally occurring antitumor agent, has been achieved by employing an oxidative spirocyclization of furan 11 as the key step. Two close analogues, 7-epi-crassalactone D (14) and 5-epi-7-epi-crassalactone D (15), also have been prepared in the course of the synthesis of (+)-crassalactone D.",10.1021/jo902055b,2009-11-19,0.6177946539604562
Synthesis,Asymmetric Synthesis of the C<sub>3</sub>-C<sub>8</sub>Fragment of Leucotrienes and Analogues,"All articles of this category An asymmetric synthesis of the C 3 -C 8 fragment of leukotrienes and analogues using the aldol-type condensation of chiral sulfinyl ester is described. Thus, starting from (3 S )-3- tert -butyldimethylsiloxy-1-(2-methoxyethoxymethoxy)-5-trimethylsilyl-4-pentyne, the corresponding methyl (2 Z ,4 S )-hexenoate, methyl (4 R )-hexanoate, (2 Z ,4 S )- and (2 E ,4 S )-2-hexenal derivatives were prepared. Several molecules prepared during this work were shown to be important intermediates in the synthesis of various natural products.",10.1055/s-1991-26622,1991-01-01,0.6177903251125324
Synlett,"New and Efficient Synthesis of 6,11-Dihydro-11-ethyl-5<i>H</i>-dibenz[<i>b</i>,<i>e</i>]azepine Derivatives Starting from <i>N</i>-Benzylanilines via Amino-Claisen and Friedel-Crafts Methodologies","New and efficient synthesis of 6,11-dihydro-11-ethyl-5H-dibenz[b,e]azepine derivatives, using the key steps of BF3·OEt2-catalyzed aromatic amino-Claisen rearrangement and the intramolecular alkene Friedel-Crafts alkylation, is reported.",10.1055/s-2004-836026,2004-11-25,0.6177900285224815
Angewandte Chemie International Edition,Biomimetic Total Synthesis of (+)‐Gelsemine,"Challenging: (+)-gelsemine was synthesized from (R,R)-aziridine 1 in 25 steps with approximately 1 % overall yield. A multistep, one-pot enol-oxonium cyclization cascade was used to construct, simultaneously, the E ring, F ring, C3 stereocenter, and C7 quaternary stereocenter. This synthesis using the enol-oxonium cyclization reaction as a key step to make the cage structure has demonstrated the proposed biosynthetic pathway of the gelsemine family.",10.1002/anie.201201736,2012-04-04,0.6177840877825025
Organic Letters,Development of an Access Route to the C31−C52 Central Core of Amphidinol 3,[reaction: see text] An asymmetric synthesis of the heavily oxygenated inner sector of amphidinol 3 constituted of C31-C52 is described. The successful pathway highlights construction of the pair of identical tetrahydropyran subunits from a common intermediate.,10.1021/ol062875+,2007-01-03,0.6177713814167519
Tetrahedron,"A one-pot synthesis of 3,3′-methylenebis(2-arylamino-4H-chromen-4-one) from C-(4-oxo-4H-1-benzopyran-3-yl)-N-arylnitrone",,10.1016/j.tetlet.2009.04.087,2009-05-05,0.6177670905504121
Tetrahedron,"An efficient and convergent route towards water-soluble, chiral and amphiphilic macrocycles",,10.1016/s0040-4039(01)00301-x,2001-04-01,0.617764313934821
Organic Process Research & Development,"Chemical Development of the Casein Kinase I - Epsilon Inhibitor: 3-(3-Fluorophenyl)sulfanyl-1<i>H</i>-pyrrolo[3,2-<i>b</i>]pyridine-2-carboxylic Acid Amide","The development of a scalable process for 3-arylsulfanyl-1 H -pyrrolo[3,2- b ]pyridine-2-carboxylic acid amides ( 1 ), potent casein kinase I inhibitors, is described. The rapid identification of suitable reaction conditions expedited the lab scale synthesis of drug substances for early toxicological evaluations. Further improvements were made to achieve a safe and cost-effective process to meet increasing demands for drug substances to support clinical studies. This paper describes the synthesis at multikilogram scale.",10.1021/op200171a,2011-08-03,0.6177534486166075
European Journal of Organic Chemistry,Total Synthesis of New 8‐(Arylmethyl)berbines,"Abstract The total synthesis of the natural compound (8 S *,14 S *)‐8‐(4′‐hydroxybenzyl)‐2,3‐dimethoxyberbin‐10‐ol and its C‐8 epimer has been conveniently developed by making use of the diastereoselective Stevens rearrangement of the corresponding N ‐(arylmethyl)berbinium salts as the key step.",10.1002/ejoc.200901081,2009-12-11,0.6177470726635623
Organic Process Research & Development,Process Development and Large-Scale Synthesis of BTK Inhibitor BIIB068,"Chemical process development efforts leading to multikilogram production of BIIB068 hemiadipate are discussed. Process optimization resulted in (1) removal of transition metal from the process, (2) a streamlined process with significantly improved overall yield, and (3) appropriate impurity control (including potential mutagenic impurities), which enabled delivery of quality material for toxicology studies and clinical trials.",10.1021/acs.oprd.0c00087,2020-04-21,0.617745088933744
Tetrahedron,Genesis of thiacalixarenes: a one-pot highly efficient synthesis of TC4A,,10.1016/j.tetlet.2008.03.052,2008-03-15,0.6177445416260213
Journal of Organic Chemistry,Evolutionary Efforts in the Total Synthesis of Pepluacetal,"Pepluacetal is a structurally unique pepluanol family Euphorbia diterpenoid bearing an all-carbon [5–4–7–3] tetracyclic backbone. We describe herein the detailed process of the total synthesis of pepluacetal through the evolution of synthetic strategies. In the final successful strategy, a photoinduced Wolff rearrangement/lactonization cascade reaction gives access to the cyclobutane moiety; a ring-closing metathesis/cyclopropanation sequence rapidly builds up the [7–3] bicycle, and a Rh-catalyzed carbenoid insertion of the cyclobutane methylene C(sp 3 )-H bond, followed by ring-opening manipulations, introduces the three-carbon branched side chain stereoselectively in a remote traceless stereochemical relay fashion. The synthesis demonstrates excellent control of stereo-, regio-, and chemoselectivities. Moreover, the synthetic route could be performed on a large scale and optimized to a shorter version by running successive reactions in one pot, thus providing a general and practical approach to access pepluacetal.",10.1021/acs.joc.5c00974,2025-07-21,0.6177295883912827
Synthesis,"Improved Synthesis of (+)-Dehydrobaimuxinol, (-)-Isobaimuxinol and (-)- Baimuxinol from (-)-Carvone","All articles of this category An improved synthesis of (+)-dehydrobaimuxinol (1) , (-)-isobai- muxinol (2) and (-)-baimuxinol (3) (2-hydroxymethyl-6,10,10-trimethyl -11-oxatricyclo[7.2.1.0 1.6 ]dodecanes) has been described starting from (-)-Carvone ( p -mentha-6,8-dien-2-one) (4) . The key step is the regiospecific allylic oxidation of α-agarofuran (7) by selenium(IV) oxide.",10.1055/s-1992-26299,1992-01-01,0.6176896711783233
Journal of Organic Chemistry,Synthesis and Hybridization Studies of 2‘-Amino-α-L-LNA and Tetracyclic “Locked LNA”,"A convergent route to a new class of locked nucleic acids, i.e., 2'-amino-alpha-L-LNA, has been developed. The optimized synthetic route to the corresponding phosphoramidite building block of thymine proceeds in 4% overall yield over 15 steps from the starting diol. Crucial synthetic steps include (a) introduction of a C2-azido group prior to nucleobase coupling, (b) Vorbrüggen glycosylation primarily affording the desired alpha-anomer, (c) separation of alpha-L-ribo- and beta-L-ribo-configured bicyclic nucleosides, and (d) selection of a suitable protecting group to avoid intramolecular Michael addition of the C2'-amino group onto the C6-position. Incorporation of a 2'-amino-alpha-L-LNA monomer into oligodeoxyribonucleotides results in modest changes in thermal stability with complementary DNA, whereas significant increases in thermal stability are observed with RNA complements along with excellent Watson-Crick discrimination. These results, along with the flexibility of the synthetic strategy allowing chemoselective N2'-functionalization at a late stage, render 2'-amino-alpha-L-LNA a promising building block for nucleic acid based nanobiotechnology and therapeutics. A slight modification in strategy facilitated the synthesis of the corresponding phosphoramidite building blocks of Michael adducts, which due to their tetracyclic skeletons exhibit a conformationally restricted furanose ring and glycosidic torsion angle (anti-range). Incorporation of such a ""locked LNA"" monomer into oligodeoxyribonucleotides results in large decreases in thermal affinity toward DNA/RNA complements.",10.1021/jo060331f,2006-04-29,0.6176875631885685
Tetrahedron,Novel synthesis of a mixed phosphonic anhydride. A route to carboxylic acid derivatives from a methyl ketone,,10.1016/0040-4039(94)88527-3,1994-12-01,0.617683758042905
Organic Letters,"Total Syntheses of Aspidospermidine, <i>N</i> -Methylaspidospermidine, <i>N</i> -Acetylaspidospermidine, and Aspidospermine via a Tandem Cyclization of Tryptamine-Ynamide","The total syntheses of aspidospermidine, N -methylaspidospermidine, N -acetylaspidospermidine, and aspidospermine were achieved from a common pentacyclic indoline intermediate. The common pentacyclic indoline intermediate was synthesized on a gram scale through a Stork-enamine alkylation of 1 H -pyrrolo[2,3- d ]carbazole derivatives, which were prepared through a Brønsted acid-catalyzed tandem cyclization of tryptamine-ynamide. The scalable synthesis of 1 H -pyrrolo[2,3- d ]carbazole afforded facile access and a practical approach to the Aspidosperma indole alkaloid family.",10.1021/acs.orglett.1c02287,2021-08-02,0.6176829186162486
Journal of the American Chemical Society,"Convergent, enantiospecific total synthesis of the novel cyclodepsipeptide (+)-jasplakinolide (jaspamide)","Jasplakinolide (l),2 a novel cyclodepsipeptide isolated from a soft-bodied sponge, Jaspis sp., contains a new amino acid, 2-OH bromoabrine, possessing the unnatural D configuration and the rare amino acid (J?)-jS-tyrosine.3The potent insecticidal, antifungal, and anthelminthic properties2 of jasplakinolide have been responsible for considerable synthetic activity in both industrial and academic laboratories.We wish to record the first total synthesis of (+)-jasplakinolide.The approach detailed below is both highly convergent and enantiospecific.Our strategy for elaboration of jasplakinolide centered around the coupling of dipeptide 2 with the L-alanine derived acyclic fragment 3. Construction of dipeptide 2 necessitated prior de- velopment of synthetic routes to the unnatural amino acids, (J?)-0-tyrosine and D-bromoabrine.",10.1021/ja00213a050,1988-03-01,0.6176812238277921
European Journal of Organic Chemistry,The Pseudotransannular Ring Opening of 1‐Aminocyclohept‐4‐ene‐derived Epoxides in the Synthesis of Tropane Alkaloids: Total Synthesis of (±)‐Ferrugine,Abstract We have optimized a synthetic approach to (±)‐Ferrugine in 8 steps starting from 5‐aminocyclohept‐1‐ene and using the Brønsted acid‐catalyzed pseudotransannular ring‐opening of the epoxide derived from this cycloheptene as the key step for the construction of the 8‐azabicyclo[3.2.1]octane central core. While attempting the enantioselective synthesis of this natural product from enantiopure 2‐hydroxy‐8‐azabicyclo[3.2.1]octane we have found that this compound shows a pronounced tendency to racemize via an achiral symmetric aziridinium intermediate. This racemization side process has been studied in detail using both experimental and computational methods.,10.1002/ejoc.202100332,2021-04-06,0.6176720653978937
Journal of the American Chemical Society,Palladium Catalyzed Kinetic and Dynamic Kinetic Asymmetric Transformations of γ-Acyloxybutenolides. Enantioselective Total Synthesis of (+)-Aflatoxin B<sub>1</sub> and B<sub>2</sub><sub>a</sub>,"The reaction of gamma-tert-butoxycarbonyloxy-2-butenolide with phenol nucleophiles in the presence of a Pd(0) complex with chiral ligands may be performed under conditions that favor either a kinetic resolution or a kinetic asymmetric transformation (KAT) or dynamic kinetic asymmetric transformation (DYKAT). Performing the reaction at high concentration (0.5 M) in the presence of a carbonate base favors the former, i.e., KAT; whereas, running the reaction at 0.1M in the presence of tetra-n-butylammonium chloride favors the DYKAT process. Syntheses of aflatoxin B(1) and B(2a) employs the DYKAT to introduce the stereochemistry. Starting with Pechmann condensation of the monomethyl ether of phloroglucinol, the requisite phenol nucleophile is constructed in two steps. The DYKAT proceeds with > 95% ee. A reductive Heck cyclization followed by a lanthanide catalyzed intramolecular acylation completes the synthesis of the pentacyclic nucleus in 3 steps. Reduction of the lactone provides aflatoxin B(2a) and its dehydration product B(1). This synthetic strategy creates an asymmetric synthesis of the former in only 7 steps and the latter in 9 steps. Thus, the ultimate synthetic sequence involves 3 + 5 --> 39 --> 40 --> 42 --> 43 --> 46 --> 47 --> 48 (aflatoxin B(2a)) --> 49 (aflatoxin B(1)).",10.1021/ja020988s,2003-02-14,0.6176664348761481
Journal of Organic Chemistry,Palladium(0)-Catalyzed Heteroarylation of 2- and 3-Indolylzinc Derivatives. An Efficient General Method for the Preparation of (2-Pyridyl)indoles and Their Application to Indole Alkaloid Synthesis,"Palladium(0)-catalyzed coupling of (1-(benzenesulfonyl)-2-indolyl)zinc chloride (1) and (1-(tert-butyldimethylsilyl)-3-indolyl)zinc chloride (6) with diversely substituted (alkyl, methoxy, methoxycarbonyl, nitro, hydroxy) 2-halopyridines gives the corresponding 2- and 3-(2-pyridyl)indoles [4 and 7 (or 8), respectively] in excellent yields. A series of other 3-(heteroaryl)indoles (pyrazinyl, furyl, thienyl, indolyl) have been similarly prepared from 6. The potential of some of these (2-pyridyl)indoles in alkaloid synthesis is demonstrated. Thus, from 2-(2-pyridyl)indole 4b, a new synthetic entry to the indolo[2,3-a]quinolizidine system, involving stereoselective hydrogenation of the pyridine ring with subsequent electrophilic cyclization upon the indole 3-position from an appropriately N(b)-substituted 2-(2-piperidyl)indole, is reported. For this purpose, Pummerer cyclizations have been extensively studied. Whereas the indole-unprotected sulfoxide 17 gives the corresponding indoloquinolizidine 19 in low yield and mainly undergoes an abnormal Pummerer cyclization that ultimately leads to sulfide 18, the N(a)-protected sulfoxides 24a and 24b afford the respective indoloquinolizidines 25a,b in 70% yield. On the other hand, the conversion of 3-(2-pyridyl)indole 8k into tetracyclic ketone 35 by stereoselective hydrogenation, followed by cyclization of the resulting all-cis-3-(2-piperidyl)indole 34, represents a formal synthesis of Strychnos alkaloids with the strychnan skeletal type (tubifoline, tubifolidine, 19,20-dihydroakuammicine). A similar conversion of 8j into nordasycarpidone constitutes a formal synthesis of the alkaloids of the uleine group. Reduction of nordasycarpidone leads to tetracycle 37, an advanced intermediate in a previous synthesis of tubotaiwine, a Strychnos alkaloid with the aspidospermatan skeletal type. Finally, piperidylindole 34 was transformed into tetracycle 41, an ABDE substructure of akuammiline alkaloids, by a sequence involving the skeletal rearrangement of an intermediate spiroindolenine as the crucial step.",10.1021/jo962169u,1997-05-01,0.6176513699603285
Organic Letters,"A Double Ring Closing Metathesis Reaction in the Rapid, Enantioselective Synthesis of NK-1 Receptor Antagonists",[structure: see text]. The NK-1 receptor antagonist 1 has been prepared in seven steps from phenylglycine methyl ester. The key steps are a double ring closing metathesis reaction of tetraene 7 to prepare spirocycle 6 and a reductive Heck reaction to introduce the aryl moiety. This latter reaction discriminates the olefins of compound 6 and proceeds in a highly regio- and stereoselective manner.,10.1021/ol006958g,2001-02-16,0.6176486622726987
Organic Letters,Total Synthesis of <i>cis</i>-Solamin,Synthesis of,10.1021/ol020102p,2002-06-04,0.6176461724891282
Organic Process Research & Development,Development of a Multikilogram-Scale One-Pot Albright–Goldman Oxidation/Dienol Acetate Formation Sequence for the Synthesis of Noroxymorphone from Morphine,"High Resolution Image Download MS PowerPoint Slide The syntheses of therapeutically important μ-opioid receptor antagonists such as naloxone and naltrexone use noroxymorphone as a key late-stage intermediate, which is manufactured from the poppy-derived alkaloids oripavine or thebaine. However, it would be advantageous to instead use morphine as the starting material, which is cheaper and more abundant. In this paper, we describe the conversion of morphine into a dienol acetate required for installation of the C14 hydroxyl group of noroxymorphone. Our approach is more efficient than previously described approaches and uses a one-pot Albright–Goldman oxidation/dienol acetate formation sequence of an allylic alcohol as the key feature. This synthesis has been successfully applied on multikilogram scales. A brief investigation of the scope of the one-pot Albright–Goldman oxidation/dienol ester formation on other substrates is also described.",10.1021/acs.oprd.5c00248,2025-10-16,0.6176428929807102
Tetrahedron,"Stereoselective synthesis of polyhydroxylated pyrrolidines: a route to novel 3,5-bis(hydroxymethyl)pyrrolidines from 2-azabicyclo[2.2.1]hept-5-enes",,10.1016/j.tetlet.2006.08.077,2006-09-12,0.6176411702028861
Organic Letters,Total Synthesis of (+)-Neopeltolide by the Macrocyclization/Transannular Pyran Cyclization Strategy,"An 11-step synthesis of (+)-neopeltolide was developed. The C1–C7 carboxylic acid and the C8–C16 alcohol were prepared, each in six steps, from ( R )- and ( S )-epichlorohydrin, respectively. After esterification, our tandem macrocyclization/transannular pyran cyclization strategy was applied to a stereocontrolled construction of the neopeltolide macrolactone. The side chain was synthesized in six steps from ethyl 4-oxazolecarboxylate through palladium-catalyzed cross-couplings. A Mitsunobu reaction of the neopeltolide macrolactone and the side chain completed the synthesis.",10.1021/acs.orglett.2c01429,2022-06-01,0.6176397098263573
Journal of Organic Chemistry,"Synthesis of (1<i>R</i>,2<i>S</i>)-1-Amino-2-vinylcyclopropanecarboxylic Acid Vinyl-ACCA) Derivatives:  Key Intermediates for the Preparation of Inhibitors of the Hepatitis C Virus NS3 Protease","(1R,2S)-1-Amino-2-vinylcyclopropanecarboxylic acid (vinyl-ACCA) is a key building block in the synthesis of potent inhibitors of the hepatitis C virus NS3 protease such as BILN 2061, which was recently shown to dramatically reduce viral load after administration to patients infected with HCV genotype 1. We have developed a scalable process that delivers derivatives of this unusual amino acid in >99% ee. The strategy was based on the dialkylation of a glycine Schiff base using trans-1,4-dibromo-2-butene as an electrophile to produce racemic vinyl-ACCA, which was subsequently resolved using a readily available, inexpensive esterase enzyme (Alcalase 2.4L). Factors that affect diastereoselection in the initial dialkylation steps were examined and the conditions optimized to deliver the desired diastereomer selectively. Product inhibition, which was encountered during the enzymatic resolution step, initially resulted in prolonged cycle times. Enrichment of racemic vinyl-ACCA through a chemical resolution via diastereomeric salt formation or the use of forcing conditions in the enzymatic reaction both led to improvements in throughput and the development of a viable process. The chemistry described herein was scaled up to produce multikilogram quantities of this building block.",10.1021/jo050468q,2005-06-17,0.6176387381199869
Angewandte Chemie International Edition,Short Formal Synthesis of (−)‐Platencin,"Short and sweet: A five-step, protecting-group-free formal synthesis of (−)-platencin from commercially available (−)-perillaldehyde (see retrosynthetic scheme) features a highly diastereoselective Diels–Alder reaction and a ring-closing metathesis as key steps.",10.1002/anie.200801441,2008-07-05,0.6176328973893999
Synlett,An Efficient Protocol for MulticomponentStereoselective Synthesis of 3-Amino-2(1<i>H</i>)-pyridinonesUsing CeCl<sub>3</sub>˙7H<sub>2</sub>O/NaI asa Reaction Promoter,"An efficient and convenient diastereoselective synthesis of 3-amino-2(1H)-pyridinones by CeCl3˙7H2O/NaI-promoted [3+2+1] three-component coupling reactions of chalcones, 2-phen­yl-1,3-oxazolon-5-one, and amines is reported. The protocol involves sequential Michael addition, condensation, ring transformation, and acid hydrolysis. Operational simplicity, ambient temperature, high yields, and diastereoselectivity are the key features of the present synthetic protocol. The reaction is an excellent illustration of Ce(III)-catalyzed C-C and C-N bond formations in a one-pot procedure",10.1055/s-2008-1078272,2008-08-21,0.6176290064766765
Synlett,A New Chemoenzymatic Enantioselective Synthesis of Optically Active Benzothiopyran and Benzothiazepin Ring System,"All articles of this category A simple enantiocontrolled synthesis of ( R )-2-methyl-2,3-dihydro-4 H -[1]benzothiopyran-4-one and ( R )-2-methyl-2,3-dihydro-1,5 -benzothiazepin-4(5 H )-one starting from ethyl ( S )-3-hydroxybutyrate is described.",10.1055/s-1991-20758,1991-01-01,0.6176257834616308
Organic Letters,Synthesis of Polycyclic Aromatic Hydrocarbons (PAHs) via a Transient Directing Group,"In this work, an efficient synthetic route was developed to construct PAHs with diverse shape, width, and edge topology. The precursors of PAHs were obtained by using a direct arylation of arenes via a transient ligand-directed C-H functionalization strategy and the cycloaromatization was readily achieved by using a Brønsted acid catalyst. This novel route provides an opportunity to build up PAHs in a highly efficient manner.",10.1021/acs.orglett.8b03359,2018-11-20,0.6176257289608367
Journal of the American Chemical Society,Total Synthesis of (−)-Mitrephorone A,"The first synthesis of (-)-mitrephorone A is disclosed along with discussion and study of synthetic strategies. The natural product includes a highly congested hexacyclic ent-trachylobane diterpenoid framework featuring a rare, embedded oxetane. The synthetic analysis presented dissects a number of approaches for the synthesis of the central oxetane, including carbonyl-olefin photocycloadditions, Prins-type cyclizations, and oxidative ring closures. In the successful route, three [4 + 2] cycloadditions enable rapid construction of all carbocycles. A novel late-stage oxidative cyclization of a hydroxy diosphenol with Koser's reagent furnishes the pivotal oxetane moiety.",10.1021/jacs.8b09685,2018-11-09,0.6176178468622306
Tetrahedron,Viehe’s salt in a novel one pot synthesis of pyrimidines,,10.1016/j.tetlet.2004.12.069,2005-01-11,0.6175976639909762
Journal of Organic Chemistry,Two Interrelated Strategies for Cephalotaxine Synthesis,"Studies of two interrelated strategies for the synthesis of members of the cephalotaxus alkaloid family have culminated in a concise route for the preparation of the parent member cephalotaxine (1). As part of efforts exploring the use of an SET-promoted photocyclization reaction of aryl-substituted silylallyliminium salts to generate the spirocyclic DE unit of the target, we noted that attempts to generate the pentacyclic amino ketone 23 by deacylation of the enol ester 20 led to production of a mixture of 23 and the macrocyclic amino enone 24. A rapid equilibrium was shown to exist between 23 and 24, favoring the latter ring-opened form. This contrasts with the behavior of desmethylcephalotaxinone (22), a key late intermediate in several earlier cephalotaxine syntheses, which is known to exist in a ring-closed form. These observations led to the design of a second generation strategy which relies on transannular cyclization of the macrocyclic amino enedione 28. In practice, the sequence following this design transforms the known iodopiperonylethanol derivative 4 to 22 in 13 steps and a 12% overall yield and, thus, corresponds to an efficient formal synthesis of cepahalotaxine.",10.1021/jo961179s,1996-01-01,0.6175951488448598
Organic Letters,"New Methodology Toward Chiral, Non-Racemic 2,5-<i>cis</i>-Substituted Piperidines via Suzuki Cross-Coupling","1,2,3,4-Tetrahydropyridines were halogenated upon treatment with iodine to obtain the desired cross-coupling precursors. Diastereoselective hydrogenation of Suzuki cross-coupling adducts allowed the facile asymmetric synthesis of 2,5-cis-substituted piperidines in five steps from readily available pyridine.",10.1021/ol061415d,2006-08-01,0.6175907186795645
Journal of Organic Chemistry,Total Synthesis of (−)-Senepodine G and (−)-Cermizine C,"An efficient, stereospecific synthesis of the alkaloids senepodine G (2) and cermizine C (1) has been completed using the BF3.Et2O-promoted stereospecific addition of Me2CuLi to alpha,beta-unsaturated lactam 6 to provide lactam 3, the addition of MeMgBr followed by HCl to convert 3 to senepodine G (2) (six steps, 40% overall yield), and the stereospecific NaBH4 reduction of 2 to give cermizine C (1) (seven steps, 40% overall yield).",10.1021/jo062067w,2007-01-04,0.6175902834442073
Tetrahedron,"Highly regioselective formation of bromohydrins by reaction of epoxy-azetidinones with MgBr2: An alternative route to 4-bromomethylcarbonylmethyl-2-azetidinone, a key carbapenem precursor",,10.1016/s0040-4039(00)80715-7,1988-01-01,0.617589861892821
Organic Letters,Formal Synthesis of Premisakinolide A and C(19)–C(32) of Swinholide A via Site-Selective C–H Allylation and Crotylation of Unprotected Diols,"Using stereo- and site-selective C-H allylation and crotylation of unprotected diols, an intermediate in the synthesis of premisakinolide A (bistheonellic acid B) that was previously made in 16-27 (LLS) steps is now prepared in only nine steps. This fragment also represents a synthesis of C(19)-C(32) of the actin-binding macrodiolide swinholide A.",10.1021/acs.orglett.5b02056,2015-09-16,0.6175772760505855
Journal of Organic Chemistry,"Synthesis of Tri-, Hexa-, and Nonasaccharide Subunits of the Atypical O-Antigen Polysaccharide of the Lipopolysaccharide from Danish <i>Helicobacter </i><i>pylori</i> Strains","Synthesis of trisaccharide repeating unit, -->3)-alpha-D-Rhap-(1-->2)-alpha-D-Manp3CMe-(1-->3)-alpha-L-Rha p-(1-->, and its dimeric hexa- and trimeric nonasaccharide subunits of the atypical O-antigen polysaccharide of the lipopolysaccharide from Danish H. pylori strains D1, D3, and D6 has been accomplished. Successful synthesis of the hexasaccharide and the nonasaccharide was possible by dimerization and trimerization of the suitably protected trisaccharide repeating unit, in which three monosaccharide moieties were arranged in a proper order by placing the sterically demanding 3-C-methyl-D-mannose moiety in between D- and L-rhamnoses. Key steps include the coupling of three monosaccharide moieties and dimerization and trimerization of the trisaccharide unit by glycosylations employing the 2'-carboxybenzyl glycoside method. Also presented is a method for the synthesis of the novel branched sugar, 3-C-methyl-D-mannose moiety by elaboration of its equatorial hydroxyl and axial methyl groups at C-3' in the disaccharide stage.",10.1021/jo701531x,2007-11-16,0.6175717067766864
Organic Letters,Total Synthesis of Nominal Lyngbouilloside Aglycon,The first enantioselective total synthesis of the originally assigned structure of lyngbouilloside aglycon has been achieved using a particularly flexible route featuring an acylketene macrolactonization of a tertiary methyl carbinol as the key step. Comparison of the C13 chemical shifts of our synthetic aglycon with the ones pertaining to natural lyngbouilloside and lyngbyaloside C resulted in a possible stereochemical reassignment of the C11 stereogenic center.,10.1021/ol203064r,2011-12-07,0.6175663143007252
Journal of Organic Chemistry,Utilization of the Intramolecular Cycloaddition−Cationic π-Cyclization of an Isomünchnone Derivative for the Synthesis of (±)-Lycopodine,"A new annulation sequence leading to the tetracyclic skeleton of the Lycopodium family of alkaloids is effected by using the tandem cycloaddition-cationic pi-cyclization reaction of an isomünchnone dipole as the key strategic element. Synthesis of the required alpha-diazo imide precursor involved treating 5-methylcyclohex-2-en-1-one with the organocopper reagent derived from 3-methoxybenzyl chloride in the presence of chlorotrimethylsilane. Ozonolysis of the resulting silyl enol ether followed by a Wittig reaction and conversion to the desired alpha-diazo imide was carried out using standard malonylacylation and diazotization procedures. Treatment of the alpha-diazo imide with rhodium(II) perfluorobutyrate afforded a transient 1,3-dipole which subsequently cycloadded across the tethered pi-bond. The resulting cycloadduct was treated with BF(3).2AcOH to give a rearranged tetracyclic compound derived from a Pictet-Spengler-type cyclization of an N-acyliminium ion. The rearranged product was subsequently converted into a key intermediate previously used for the synthesis of (+/-)-lycopodine.",10.1021/jo960829p,1997-01-01,0.6175579963099579
Journal of Organic Chemistry,Asymmetric Total Syntheses of Rhynchophylline and Isorhynchophylline,"The asymmetric total syntheses of (-)-rhynchophylline and (+)-isorhynchophylline were achieved in 17 and 16 steps, respectively, from butanal and ethyl acrylate. Our synthesis features Carreira ring expansion to construct the tetracyclic spirooxindole core in high diastereoselectivity and the use of Bosch's chiral lactam for preparation of enantioenriched cyclic imine.",10.1021/acs.joc.9b01977,2019-08-16,0.6175517483702345
European Journal of Organic Chemistry,"Enantioselective Total Syntheses of (–)‐Isonitramine, (–)‐Sibirine, and (+)‐Nitramine by Ring‐Closing Metathesis","Abstract Concise enantioselective total syntheses of naturally occurring 2‐azaspiro[5,5]undecan‐7‐ol ( Nitraria ) alkaloids viz. (–)‐isonitramine, (–)‐sibirine, and (+)‐nitramine are accomplished in 42, 38, and 25 % overall yield, respectively, in six steps starting from enantiomerically pure ( S )‐methyl 3‐allyl‐2‐oxo‐1,2,3,6‐tetrahydropyridine‐3‐carboxylate (&gt;99 % ee ). The key feature of the syntheses involves diastereoselective Hosomi–Sakurai allylation followed by ring‐closing metathesis.",10.1002/ejoc.201101256,2011-10-31,0.6175509266497975
Journal of Organic Chemistry,"A Versatile Stereoselective Synthesis of <i>e</i><i>ndo,</i><i>e</i><i>xo</i>-Furofuranones:  Application to the Enantioselective Synthesis of Furofuran Lignans","A new stereoselective route to endo,exo-2,6-diarylfurofuranones has been developed using Mn(III)-mediated intramolecular cyclopropanation and C-H insertion reactions as key C-C bond-forming steps. Mn(III)-mediated oxidative cyclization of acetoacetate derivative 11 afforded 1-acetyl-4-aryl-3-oxabicyclo[3.1.0]hexan-2-one (12) with excellent diastereocontrol (d.r. 22:1). Subsequent Lewis acid-catalyzed opening of the activated cyclopropane ring present in 12 with benzylic alcohols then gave alpha-acetyl-gamma-butyrolactones 16 and 18-20, which reacted efficiently with in situ-generated TfN(3) to secure the key alpha-diazo-gamma-butyrolactones 22-25. Highly stereoselective rhodium-catalyzed C-H insertion reactions of diazolactones 22-25 completed the synthesis of endo,exo-2,6-diarylfurofuranones 26-29 in overall yields ranging from 41 to 48% from 1-phenylallyl alcohol (+/-)-10. The approach developed for the furofuranones 26-29 was then applied to the asymmetric syntheses of four furofuran lignans, (+)-xanthoxylol (1), (+)-methylxanthoxylol (2), (+)-epipinoresinol (3), and (+)-epieudesmin (4), starting from enantiomerically enriched 1-arylallyl alcohol (S)-31.",10.1021/jo035365r,2003-12-12,0.6175370260920706
Journal of Organic Chemistry,"Cyclization of Methyl-Coumalate-Derived Methyl 1-Benzamido-6-oxo-1,6-dihydropyridine-3-carboxylates: Assembly of the [1,2,4]Triazolo[1,5-<i>a</i>]pyridine Ring System","An efficient three-step synthesis of a series of fused bicyclic s-[1,2,4]triazolo[1,5-a]pyridines 1 was accomplished utilizing novel intermediates derived from inexpensive, commercially available hydrazides A and methyl coumalate B. A significant feature of this approach was the formation of a dihydrazide intermediate 2, bypassing the need for oxidative N-N bond formation in the 1,2,4-triazole synthesis. Further purification of the dihydrazides 2, beyond simple isolation, proved to be unnecessary owing to the impurity rejection afforded by the crystalline oxadiazolium salts 3. Additionally, the prepared oxadiazolium perchlorate salts showed excellent moisture stability, an unusual feature in compounds of this type.",10.1021/acs.joc.7b00873,2017-05-12,0.6175242178387946
Tetrahedron,Regiospecific synthesis of linear quinone systems: efficient convergent synthesis of anthracycline intermediates,,10.1016/s0040-4039(01)86101-3,1979-01-01,0.6175219943963358
Organic Letters,Concise Formal Synthesis of (+)-Neopeltolide,"A concise formal synthesis of (+)-neopeltolide (1) has been accomplished. The synthesis demonstrated high atom efficiency employing only one step of functional group protection. Key steps involved iridium-catalyzed double asymmetric carbonyl allylation, palladium-catalyzed intramolecular alkoxycarbonylation, ruthenium-catalyzed olefin isomerization, and ring-closing metathesis.",10.1021/ol2025718,2011-10-13,0.6175205634898632
Journal of Organic Chemistry,Application of Vicarious Nucleophilic Substitution to the Total Synthesis of <i>dl</i>-Physostigmine,"A concise, highly efficient formal total synthesis of dl-physostigmine is described, using a relatively simple method that should be adaptable to the synthesis of homologous members of this type of alkaloid. The key step in the synthesis is a new vicarious nucleophilic substitution reaction between p-nitroanisole and a C-silylated derivative of N-methylpyrrolidinone. Subsequent conversion of the initial adduct to the tricyclic framework of physostigmine follows a well-established protocol and provides the key intermediate 8 in high yield. The vicarious nucleophilic substitution reaction has also been extended to six-membered lactams, with encouraging results.",10.1021/jo026438u,2003-07-04,0.6175183818112256
Tetrahedron,"A convenient synthetic route to 2-aryl-N-tosylazetidines and their ZnX2 (X=I, OTf) mediated regioselective nucleophilic ring opening reactions: synthesis of γ-iodoamines and tetrahydropyrimidines",,10.1016/j.tetlet.2006.05.058,2006-06-13,0.6175168712088265
Synlett,Convergent Synthesis of the C18-C30 Fragment of Amphidinol 3,"The C18-C30 fragment of amphidinol 3 has been synthesized in a convergent fashion by employing two asymmetric Sharpless dihydroxylations, a Julia-Kocienski olefination and a Wittig reaction as the key steps.",10.1055/s-0029-1217754,2009-09-03,0.6175159466177478
Tetrahedron,Selective synthesis of α-methylenyl zirconacyclopentene via cross-coupling of alkyne and allene,,10.1016/j.tetlet.2010.06.134,2010-07-06,0.6175113591042592
Journal of Organic Chemistry,Synthesis and Configurational Assignment of the Amino Alcohol in the Eastern Fragment of the GE2270 Antibiotics by Regio- and Stereoselective Addition of 2-Metalated 4-Bromothiazoles to α-Chiral Electrophiles,"A synthesis of the eastern fragment of the thiazole peptide GE2270 A (1) has been developed. The synthetic approach relies on the regioselective functionalization of 2,4-dibromothiazole (5) via metalation and nucleophilic addition (at C2) or palladium-mediated cross-coupling (at C2 or C4). The stereochemistry at the N-bearing stereocenter was established by coupling of 2-metalated 4-bromothiazoles (4) to enantiomerically pure mandelic acid derivatives. Both the erythro (2) and threo (3) configurated amino alcohols were prepared with high diastereoselectivities depending on the electrophile employed. More specifically, the threo-configurated (S,R)-4-bromothiazolyl beta-amino alcohol 6 was synthesized from O-TBS protected (R)-mandelonitrile in 62% yield. Its N-PMB protected (R,S)-enantiomer 20 was obtained from O-TBS protected (S)-mandelic aldehyde in 67% yield. The erythro-configurated (S,S)-4-bromothiazolyl beta-amino alcohol 29 was prepared from O-TBS protected (S)-ethyl mandelate in four steps and 33% overall yield. The bithiazole moiety in the desired products 2 and 3 was finally established by the regioselective Negishi coupling of 2,4-dibromothiazole (5) and the 4-zincated, N-Boc protected thiazole derivatives of the diastereomeric 4-bromothiazolyl beta-amino alcohols 6 and 29.",10.1021/jo060462g,2006-05-17,0.6175074863894718
Journal of Organic Chemistry,Concise Stereocontrolled Formal Synthesis of (±)-Quinine and Total Synthesis of (±)-7- Hydroxyquinine via Merged Morita−Baylis−Hillman−Tsuji−Trost Cyclization,"Concise stereoselective syntheses of (+/-)-quinine and (+/-)-7-hydroxyquinine are achieved using a catalytic enone cycloallylation that combines the nucleophilic features of the Morita-Baylis-Hillman reaction and the electrophilic features of the Tsuji-Trost reaction. Cyclization of enone-allyl carbonate 11 delivers the product of cycloallylation 13 in 68% yield. Diastereoselective conjugate reduction of the enone 13 (>20:1 dr) followed by exchange of the N-protecting group provides the saturated N-Boc-protected methyl ketone 19, which upon aldol dehydration provides quinoline containing enone 15, possessing all carbon atoms of quinine. Exposure of ketone 15 to L-selectride enables diastereoselective carbonyl reduction (>20:1 dr) to furnish the allylic alcohol 16. Stereoselective hydroxyl-directed epoxidation using an oxovanadium catalyst modified by N-hydroxy-N-Me-pivalamide delivers epoxide 17 (17:1 dr). Cyclization of the resulting amine-epoxide 17 provides (+/-)-7-hydroxyquinine in 13 steps and 11% overall yield from aminoacetaldehyde diethyl acetal. Notably, highly stereoselective formation of five contiguous stereocenters is achieved through a series of 1,2-asymmetric induction events. Deoxygenation of the N-Cbz-protected allylic acetate 22 provides olefin 23, which previously has been converted to quinine. Thus, (+/-)-quinine is accessible in 16 steps and 4% overall yield from commercial aminoacetaldehyde diethyl acetal.",10.1021/jo802165k,2008-11-07,0.6175051933299364
Journal of the American Chemical Society,Total Synthesis of (+)-Resiniferatoxin via a Pyridinium Salt Photorearrangement,"We report a total synthesis of (+)-resiniferatoxin (RTX) that leverages both the ground-state and excited-state reactivity of pyridinium to assemble its highly oxidized 5/7/6-fused tricyclic core. A key strategic element is the development of a practical protocol for the in situ formation of pyridinium trifluoromethanesulfonate salts via mild methylation of densely substituted pyridines, followed by a ring-contracting photorearrangement in either batch or continuous flow settings. Rapid, one-pot elaboration of the resulting aziridine intermediate provides gram-scale access to advanced intermediates, which represents a modular route to highly functionalized five-membered carbocycles embedded in fused-ring scaffolds, thereby facilitating biological studies and analog development of RTX.",10.1021/jacs.5c16410,2025-11-05,0.6175029854204414
Organic Letters,"Enantioselective Synthesis of a <i>trans</i>-7,8-Dimethoxycalamenene","trans-7,8-dimethoxy-11,12-dehydrocalamenene, a projected intermediate for the total synthesis of marine serrulatane and amphilectane diterpenes, was efficiently synthesized. Starting from a styrene, asymmetric Rh-catalyzed hydroboration using a novel chiral P,P-bidentate ligand afforded an organoboron intermediate (93% ee) which was directly used for C-C bond formation (double homologation, Suzuki coupling). The 1,4-trans-disubstituted tetralin skeleton was selectively formed by a Friedel-Crafts-type cationic cyclization under strictly aprotic conditions (Me2AlCl) to suppress a remarkable proton-catalyzed disproportionation via diastereoselective hydride transfer.",10.1021/ol071228v,2007-08-01,0.6174968717270789
Journal of Organic Chemistry,Stereoselective Total Synthesis of (+)-Cardiobutanolide,"Stereoselective synthesis of styryllactone (+)-cardiobutanolide was accomplished in good overall yield from d-(-)-tartaric acid. Key features of the synthesis include the elaboration of a gamma-hydroxy butyramide obtained from the dimethylamide of tartaric acid, involving a combination of the addition of 1,3-dithian-2-yllithium and stereoselective reduction.",10.1021/jo7025614,2008-03-07,0.617493277424203
Tetrahedron,Synthesis of aplysiatoxin: stereoselective synthesis of key fragments,,10.1016/s0040-4039(00)93448-8,1991-09-01,0.6174823326616142
Synthesis,"Contemporary Synthetic Strategies towards Secosteroids, abeo-Steroids, and Related Triterpenes","Steroids have long been sought after as synthetic targets. Their rearranged counterparts, though, have only recently received more attention, when isolation and biological testing programs revealed several molecular entities that were both structurally intriguing as well as biologically relevant. This review will highlight contemporary synthetic approaches towards the growing class of seco- and abeo-steroids and some related triterpenoid natural products. 1 Introduction 2 Cyclocitrinol 2.1 Li’s Synthesis of Cyclocitrinol 2.2 Gui’s Synthesis of Cyclocitrinol 3 Strophasterol 3.1 Heretsch’s Synthesis of Strophasterol A 3.2 Kuwahara’s Synthesis of Strophasterols A and B 4 Pleurocin A/Matsutakone and Pleurocin B 4.1 Heretsch’s Synthesis of Pleurocin A/Matsutakone and Pleurocin B 5 Aplysiasecosterol A 5.1 Li’s Synthesis of Aplysiasecosterol A 6 Glaucogenins C and D 6.1 Tian’s Syntheses of 5,6-Dihydro-glaucogenin C and Glaucogenin D 7 Physalin B 7.1 Sodeoka’s Synthesis of the DFGH Ring System of Physalin B 8 Limonin 8.1 Hirama’s Synthesis of (±)-Limonin 9 Schiglautone A 9.1 Ding’s Synthesis of (±)-atrop-Schiglautone A 10 Conclusion",10.1055/s-0037-1611576,2019-04-16,0.6174737042313825
Organic Letters,Formal Synthesis of Actin Binding Macrolide Rhizopodin,"Formal synthesis of an actin binding macrolide rhizopodin was achieved in 19 longest linear steps. The key features of the synthesis include a stereoselective Mukaiyama aldol reaction, dual role of a Nagao auxiliary (first, as a chiral auxiliary of choice for installing hydroxy centers and, later, as an acylating agent to form an amide bond with an amino alcohol), late stage oxazole formation, and Stille coupling reactions.",10.1021/ol5008179,2014-04-10,0.6174656010660748
Tetrahedron,"Synthetic entry into a new type of prostaglandin: 6(9α),6(11α)-dioxido-15S-hydroxyprost-13E-enoic acid methyl ester",,10.1016/s0040-4039(01)94813-0,1978-01-01,0.6174442953824076
Tetrahedron,"Synthetic entry into a new type of prostaglandin: 6(9α),6(11α)-dioxido-15S-hydroxyprost-13E-enoic acid methyl ester",,10.1016/0040-4039(78)80018-5,1978-07-01,0.6174442953824076
Tetrahedron,Novel efficient synthesis of an enantiomeric pair of tricycloillicinone,,10.1016/s0040-4039(03)01739-8,2003-09-01,0.6174408892977482
Synthesis,A Simple and Efficient Route to Chaetomellic Anhydride A: A Potent Natural Ras Farnesyl-Protein Transferase Inhibitor,"A new and efficient approach to chaetomellic anhydride A has been devised starting from 2,2-dichloropalmitic acid. This involves the atom transfer radical cyclization of an N-alkyl-N-(3-chloro-2-propenyl)amide followed by rearrangement of the resulting trichloro-pyrrolidin-2-one.",10.1055/s-2004-829116,2004-06-23,0.6174354317084088
Journal of Organic Chemistry,Studies toward the Total Synthesis of Dihydrolycolucine. Preparation of AB and CEF Ring Fragments,A strategy for the synthesis of the lycopodium alkaloid dihydrolycolucine (1) has been investigated. Synthetic routes were developed based on N-acylpyridinium salt chemistry to prepare target fragments 3 and 4 that could ultimately converge to the natural product. Key reactions include IMDA cycloadditions and retro-Mannich ring-openings to form both the AB and the EF ring fragments. The ring C precursor was prepared using pyridine substitution and directed lithiation chemistry. A Suzuki cross-coupling of rings C and EF led to the CEF ring fragment. Initial attempts at closure of the seven-membered D ring were unsuccessful.,10.1021/jo500878v,2014-05-19,0.6174343756322808
Journal of Organic Chemistry,A Total Synthesis of the Methyl Glycoside of Ganglioside GM<sub>1</sub>,"The total synthesis of the methyl glycoside of GM(1) (1b) has been accomplished. The key step in the synthesis involves the sulfonamidoglycosidation reaction, which is used to create a beta-linkage leading to a GalNAc residue joined to the C4 hydroxyl group of a galactose unit of a C3 sialylated lactosyl moiety. The ""proximal hydroxyl"" directing effect, which has been postulated before, manifests in this context as well leading to the preponderant formation of the beta-glycoside. Together with asialo GM(1) and other substructures, the GM(1) methyl glycoside has been submitted for biological assays as potential ligands for bacterial and viral infection sites.",10.1021/jo9912496,1999-12-12,0.6174228918779835
Journal of Organic Chemistry,First Atropo-Divergent Total Synthesis of the Antimalarial Korupensamines A and B by the “Lactone Method”,"The stereoselective total synthesis of the antimalarial korupensamines A (1a) and B (1b) by application of the ""lactone method"" is described. Key steps of this first atropo-selective access to 5,8'-coupled naphthylisoquinoline alkaloids were the regioselective intramolecular coupling of ester 8 to give the configurationally labile lactone-bridged biaryl 9 and its atropisomer-selective cleavage with a variety of chiral and achiral H-nucleophiles, yielding the configurationally stable P-diol 10a or, optionally, the M-product 10b. From the axially chiral phenylisoquinolines thus obtained atropo-diastereodivergently, the authentic natural naphthylisoquinolines with the respective axial configurations, korupensamines A (1a) and B (1b), were obtained by completion of the second naphthalene ring, starting from the previous ""bridgehead"" C1 unit.",10.1021/jo991634v,2000-03-08,0.6174147721189357
Journal of Organic Chemistry,Synthetic Studies on FNC-RED and Its Analogues Containing an All <i>syn</i>-Cyclopentanetetrol Moiety,FNC-RED exhibits innate immune receptor Toll-like receptor 4 (TLR4)/myeloid differentiation factor-2 (MD2) stimulatory activity. We have developed a divergent synthetic route to FNC-RED derivatives containing various alkyl side chains. Key features of the synthetic study include stepwise palladium catalyzed cross-coupling reactions and the construction of an all syn -cyclopentanetetrol moiety.,10.1021/acs.joc.9b02101,2019-09-11,0.6174113335882391
Reaction Chemistry & Engineering,Two-step synthesis of amino-methyl- <i>N</i> -phenylcarbamate from toluidine: new preparative method and mechanism,"A new two-step route, i.e. , p -toluidine first reacted with dimethyl carbonate to form metholylcarbamate (MTCM), and then MTCM further converted to amino-methyl- N -phenylcarbamate (TMC), was realized in this work.",10.1039/d5re00246j,2025-09-10,0.6174050960859186
Organic Letters,First Total Synthesis of Dragmacidin A via Indolylglycines,"The first total synthesis of dragmacidin A has been accomplished using condensation of two indolylglycines followed by cyclization and reduction. The general and practical method for synthesis of indolylglycines via Wittig reaction, azide addition, and reduction from indolin-3-ones is also described.",10.1021/ol006394g,2000-08-31,0.6174016696821358
Journal of the American Chemical Society,General Synthetic Approach to Diverse Taxane Cores,"Chemical synthesis of natural products is typically inspired by the structure and function of a target molecule. When both factors are of interest, such as in the case of taxane diterpenoids, a synthesis can both serve as a platform for synthetic strategy development and enable new biological exploration. Guided by this paradigm, we present here a unified enantiospecific approach to diverse taxane cores from the feedstock monoterpenoid ( S )-carvone. Key to the success of our approach was the use of a skeletal remodeling strategy which began with the divergent reorganization and convergent coupling of two carvone-derived fragments, facilitated by Pd-catalyzed C–C bond cleavage tactics. This coupling was followed by additional restructuring using a Sm(II)-mediated rearrangement and a bioinspired, visible-light induced, transannular [2 + 2] photocycloaddition. Overall, this divergent monoterpenoid remodeling/convergent fragment coupling approach to complex diterpenoid synthesis provides access to structurally disparate taxane cores which have set the stage for the preparation of a wide range of taxanes.",10.1021/jacs.2c10272,2022-11-08,0.6173914015113817
Organic Process Research & Development,Scale-up Synthesis of Tesirine,"This work describes the enabling synthesis of tesirine, a pyrrolobenzodiazepine antibody–drug conjugate drug-linker. Over the course of four synthetic campaigns, the discovery route was developed and scaled up to provide a robust manufacturing process. Early intermediates were produced on a kilogram scale and at high purity, without chromatography. Midstage reactions were optimized to minimize impurity formation. Late stage material was produced and purified using a small number of key high-pressure chromatography steps, ultimately resulting in a 169 g batch after 34 steps. At the time of writing, tesirine is the drug-linker component of eight antibody–drug conjugates in multiple clinical trials, four of them pivotal.",10.1021/acs.oprd.8b00205,2018-08-02,0.6173685826717468
Journal of Organic Chemistry,Total Synthesis of Quinolizidine (−)-217A,We report here the construction of quinolizidine ring systems by intramolecular cyclization of suitable functionalized piperidines via a reductive amination sequence. This reaction proceeds with a total stereocontrol at C4. The preparation of the piperidine precursors is based on a chain elongation of a piperidine aldehyde either by aldolization or by Wittig reaction. We applied this second route to the total synthesis of quinolizidine (-)-217A from (S)-methyl 2-((S)-1-((R)-1-phenylethyl)piperidin-2-yl)propanoate 5.,10.1021/jo101668k,2010-10-25,0.6173513643903902
Synthesis,Facile Synthesis of the Isoquinoline Alkaloids Doryanine and Oxyhydrastinine,"Starting from 4,5-(methylenedioxy)homophthalic acid, a concise and efficient synthesis of the isoquinoline alkaloids doryanine and oxyhydrastinine is described via the corresponding homophthalimide utilizing a one-pot regioselective reductive dehydration and catalytic hydrogenation pathway.",10.1055/s-0033-1341158,2014-04-10,0.6173395360427619
Journal of Organic Chemistry,A Synthetic Approach to Ervatamine-Silicine Alkaloids. Enantioselective Total Synthesis of (−)-16-Episilicine,"Starting from an appropriate unsaturated phenylglycinol-derived oxazolopiperidone lactam, the synthesis of (-)-16-episilicine is reported, the key steps being a stereoselective conjugate addition, a stereoselective alkylation, and a ring-closing metathesis reaction. This represents the first enantioselective total synthesis of an alkaloid of the silicine group.",10.1021/jo902346j,2009-12-07,0.6173067509348547
Reaction Chemistry & Engineering,Highly efficient and scalable chemoenzymatic syntheses of (R)- and (S)-lactaldehydes,"Biocatalytic asymmetric reductions have been key steps in the synthesis of 1,1-dimethoxy-2-propanone, catalyzed by suitable ketoreductases to ( <italic>S</italic> )- and ( <italic>R</italic> )-1,1-dimethoxy-2-propanol, obtained in ≥99.9% ee and excellent yield. Removal of the protecting group gave the ( <italic>S</italic> )- and ( <italic>R</italic> )-lactaldehydes in excellent yield and purity.",10.1039/c5re00009b,2015-11-06,0.6172986793306307
Organic Process Research & Development,A Cost-Efficient Synthesis of Simvastatin via High-Conversion Methylation of an Alkoxide Ester Enolate,"A cost-efficient synthesis of simvastatin ( 2 ), starting from mevinolin (lovastatin) ( 1a ) or its precursor mevinolinic acid ( 1b ), is reported. This synthesis involves the use of a new intermediate, lovastatin cyclopropylamide ( 3 ), eliminating two chemical steps of protection and deprotection of the open dihydroxy form of ( 1a ). Synthesis is based on the high-conversion methylation of an alkoxide ester enolate and involves only four chemical steps. Methylation reaction conditions have been optimized to get >99.5% conversion. Process is economical on large-scale and product ( 2 ) is obtained in 85% overall yield.",10.1021/op990187i,1999-09-03,0.6172942315330328
Journal of Organic Chemistry,"Development of a Unified Enantioselective, Convergent Synthetic Approach Toward the Furanobutenolide-Derived Polycyclic Norcembranoid Diterpenes: Asymmetric Formation of the Polycyclic Norditerpenoid Carbocyclic Core by Tandem Annulation Cascade","An enantioselective and diastereoselective approach toward the synthesis of the tetracyclic scaffold of the furanobutenolide-derived polycyclic norditerpenoids is described. Focusing on synthetic efforts toward ineleganolide, the synthetic approach utilizes a palladium-catalyzed enantioselective allylic alkylation for the construction of the requisite chiral tertiary ether. A diastereoselective cyclopropanation-Cope rearrangement cascade enabled the convergent assembly of the ineleganolide [6,7,5,5]-tetracyclic scaffold. Investigation of substrates for this critical tandem annulation process is discussed along with synthetic manipulations of the [6,7,5,5]-tetracyclic scaffold and the attempted interconversion of the [6,7,5,5]-tetracyclic scaffold of ineleganolide to the isomeric [7,6,5,5]-core of scabrolide A and its naturally occurring isomers. Computational evaluation of ground-state energies of late-stage synthetic intermediates was used to guide synthetic development and aid in the investigation of the conformational rigidity of these highly constrained and compact polycyclic structures.",10.1021/acs.joc.7b02825,2018-02-21,0.6172906906649572
Journal of the American Chemical Society,Stereoselective Total Synthesis of Nimbolide,"A stereoselective total synthesis of nimbolide has been achieved in a convergent, 11-step sequence from α-methyl-( R )-carvone. The strategy relied on a stereoselective palladium-catalyzed borylative Heck cyclization where the A-ring of the nimbolide core was constructed while simultaneously performing oxidation at C(28). Selective manipulations delivered a fully decorated decalin moiety on large scale. Then, a stereoretentive etherification reaction brought together two fragments and forged the critical C–O bond with high selectivity. Finally, a regioselective radical cyclization and late-stage lactonization completed the total synthesis of nimbolide.",10.1021/jacs.5c04899,2025-04-21,0.6172842954220042
Organic Letters,"A Novel Route to Pyrrolo[2,1-<i>c</i>][1,4]benzodiazepin-5-ones. Formal Total Synthesis of (±)-DC-81","Compounds 3a and 3b were synthesized from N-allylisatoic anhydrides 5a and 5b in six and seven steps, respectively. Synthesis of 3b constitutes a formal total synthesis of (±)-DC-81.",10.1021/ol991100g,1999-11-05,0.6172842723049927
Journal of Organic Chemistry,Synthesis of (<i>R</i>)-(+)-4-Methylcyclohex-2-ene-1-one,"A three-step synthesis of (R)-(+)-4-methylcyclohex-2-ene-1-one (1) from (R)-(+)-pulegone (3), proceeding in 44% overall yield, is described. The sequence comprises vinyl triflate formation, site-selective ozonolysis, and reduction. The route requires only one chromatographic purification and provides a convenient method to access multigram quantities of (R)-(+)-4-methylcyclohex-2-ene-1-one (1).",10.1021/jo3017956,2012-10-03,0.6172477880205787
Journal of the American Chemical Society,Stereocontrolled Total Synthesis of (+)-Vinblastine,"A stereocontrolled total synthesis of (+)-vinblastine was accomplished, featuring preparations of the two indole units by means of a novel indole synthesis via radical cyclization of thioanilide, and a stereoselective coupling of these units.",10.1021/ja0177049,2002-02-16,0.6172456068461698
Organic Letters,Scalable Total Syntheses of (±)-Catellatolactams A and B,"The first total syntheses of (±)-catellatolactams A and B, two novel ansamacrolactams, are described in 5 and 8 steps, respectively. The strategy relies on an amidation reaction to couple the acylated Meldrum’s acid and an aryl amine, a regioselective C–H insertion to construct the γ-lactam moiety, and an RCM reaction to forge the macrocycles with E -olefin. This concise and scalable synthesis provided over 200 mg of the target molecules.",10.1021/acs.orglett.3c00132,2023-02-07,0.6172305896701591
Journal of Organic Chemistry,"Efficient Synthesis of 1α-Fluoro A-Ring Phosphine Oxide, a Useful Building Block for Vitamin D Analogues, from (<i>S</i>)<i>-</i>Carvone via a Highly Selective Palladium-Catalyzed Isomerization of Dieneoxide to Dieneol","The 1alpha-fluoro A-ring phosphine oxide 1, a useful building block for fluorinated vitamin D analogues, was synthesized from (S)-carvone in 13 synthetic steps, and only five isolations, in 22% overall yield. In the key synthetic step, a highly selective palladium-catalyzed isomerization of dieneoxide 18 to dieneol 20 was achieved using an appropriately selected fluorinated alcohol as a catalytic proton source.",10.1021/jo015788y,2001-08-11,0.6172169293153832
Journal of Organic Chemistry,Prostaglandin synthesis via two-component coupling. Highly efficient synthesis of chiral prostaglandin intermediates 4-alkoxy-2-alkyl-2-cyclopenten-1-one and 4-alkoxy-3-alkenyl-2-methylenecyclopentan-1-one,", Prostaglandin Synthesis via Two-component Coupling. Highly Efficient Synthesis of Chiral Prostaglandin Intermediates 4-Alkoxy-2-alkyl-2-cyclopenten-1-one and 4-Alkoxy-3-alkenyl-2-methylenecyclopentan-1-one",10.1021/jo00258a051,1988-11-01,0.6172161542306336
Journal of Organic Chemistry,Total Synthesis of (−)-Verrucarol<sup>1</sup>,"We have achieved the total synthesis of (-)-verrucarol, a trichothecene sesquiterpenoid obtained as a hydrolysis product of the naturally occurring verrucarin A. Our total synthesis began with the previously reported enantiomerically pure bicyclic alpha-methylated gamma-lactone, which was prepared from D-glucose. The key steps for the total synthesis were (1) aldol-like carbon-carbon bond formation applied to the starting lactone using a four-carbon aldehyde as an electrophile for introduction of the quaternary stereogenic carbon sharing the B and C-rings of the trichothecene skeleton, (2) Dieckmann cyclization of the derived epsilon-ester lactone for construction of the C-ring equivalent, (3) Barton's decarboxylative oxygenation for conversion of a carboxylic acid functionality in the Dieckmann cyclization product into a hydroxyl group, (4) skeletal enlargement strategy for the crucial trichothecene skeleton construction, and (5) the final stereoselective formation of the exo-epoxy ring at the methylene carbon in the bridge constituting the B and C-rings.",10.1021/jo972309f,1998-04-01,0.617198839661515
Angewandte Chemie International Edition,Total Synthesis of Celogentin C by Stereoselective CH Activation,"A total gent: Inspired by the biosynthesis of celogentin C, a highly stereoselective and efficient palladium-catalyzed CH functionalization strategy is employed to construct the key Leu-Trp linkage of this bicyclic compound. A streamlined synthesis is completed in 23 steps from simple amino acid building blocks.",10.1002/anie.200905134,2009-12-22,0.6171940771154983
Synlett,A New Strategy for the Synthesis of Selectively Protected Spermidine and Norspermidine Derivatives,All articles of this category The synthesis of spermidine derivatives holding three independently removable N-protecting groups has been achieved from diallylamine using the key sequence: selective palladium-catalyzed monodesallylation of diallylamines/N-alkylation. Polyamine - allylamine - selective desallylation - orthogonal N-protection,10.1055/s-1996-5321,1996-01-01,0.6171933337251848
Journal of Organic Chemistry,Highly Diastereoselective Synthesis of a HCV NS5B Nucleoside Polymerase Inhibitor,"An asymmetric synthesis of HCV NS5B nucleoside polymerase inhibitor (1) is described. This novel route features several remarkably diastereoselective and high-yielding transformations, including construction of the all-carbon quaternary stereogenic center at C-2 via a thermodynamic aldol reaction. A subsequent glycosylation reaction with activated uracil via C-1 phosphate and installation of the cyclic phosphate group using an achiral phosphorus(III) reagent followed by oxidation provides 1.",10.1021/acs.joc.8b02500,2018-11-26,0.6171726907969797
Organic Process Research & Development,Process Development of 5-Fluoro-3-[3-[4-(5-methoxy-4-pyrimidinyl)-1- piperazinyl]propyl]-1<i>H</i>-indole Dihydrochloride,"5-Fluoro-3-[3-[4-(5-methoxy-4-pyrimidinyl)-1-piperazinyl]propyl]-1 H -indole dihydrochloride ( 1 ) facilitates 5-HT neurotransmission and was an antidepressant drug candidate. The development of a safe, rugged process for the large-scale, chromatography-free preparation of this compound is described. The main areas of optimization included a Fischer indole synthesis, preparation and chlorination of a monohydroxypyrimidine, and coupling of the resultant fragments to prepare the drug substance.",10.1021/op970213h,1997-07-01,0.6171704969510581
European Journal of Organic Chemistry,"Total Synthesis of Isodesmosine by Stepwise, Regioselective Negishi and Sonogashira Cross‐Coupling Reactions","Abstract Isodesmosine is a crosslinking pyridinium amino acid of elastin and is an attractive biomarker for the diagnosis of chronic obstructive pulmonary disease (COPD). In this paper, we describe the total synthesis of isodesmosine. The key features of this synthesis are stepwise and regioselective palladium‐catalyzed Negishi and Sonogashira cross‐coupling reactions for efficient introduction of amino acid segments on the pyridine ring.",10.1002/ejoc.201500449,2015-05-15,0.6171662913911807
Synthesis,Synthesis of New Paramagnetic Selenophenes,"Abstract: Starting from 3-bromo-4-formyl- or 3-bromo-4-cyano-2,2,5,5,-tetramethyl-2,5-dihydro-1H-pyrrol-1-yloxyl radicals, 2-substituted and 2,3-disubstituted 5H-selenolo[2,3-c]pyrrol-5-yloxylradicals were synthesized. The 2-(bromomethyl)-substituted 5H-selenolo[2,3-c]pyrrol-5-yloxyl derivative was a key intermediate in the synthesis of a thiol specific methanethiosulfonate spin label reagent,&#13;\na paramagnetic, selenophene ring-containing amino acid, and&#13;\na new quinazolin-4(3H)-one derivative.",10.1055/s-0029-1219758,2010-04-06,0.61714686956711
Synlett,"Concise Enantioselective Syntheses of (+)-L-733,060 and (2S,3S)-3-Hydroxypipecolic Acid by Cobalt(III)(salen)-Catalyzed Two-Stereocenter Hydrolytic Kinetic Resolution of Racemic Azido Epoxides","An efficient synthesis of the 2,3-disubstituted piperidines (+)-L-733,060 and (2 S ,3 S )-3-hydroxypipecolic acid (≥99% ee) in high optical purity from commercially available starting materials is described. The strategy involves a cobalt-catalyzed hydrolytic kinetic resolution of a racemic azido epoxide with two stereocenters and an intramolecular reductive cyclization as key reactions.",10.1055/s-0033-1340074,2013-11-12,0.6171402805204695
Journal of the American Chemical Society,Complex Target-Oriented Total Synthesis in the Drug Discovery Process:  The Discovery of a Highly Promising Family of Second Generation Epothilones,"The total synthesis of a family of (E)-9,10-dehydro derivatives of epothilone D (i.e., 12,13-desoxyepothilone B) is described. The route is particularly concise and amenable to production of new congeners. Furthermore, the chemistry described herein constitutes a major simplification in the total synthesis of EpoD, which is in human clinical trials. This new family of epothilones shows major advantages in terms of their potency and pharmacostability relative to the wild-type saturated analogues in the D series. From the perspective of compound availability through synthesis, potency, and pharmacokinetic properties, these compounds could well warrant advancement to clinical evaluation in humans.",10.1021/ja029695p,2003-02-06,0.617135755006517
Organic Letters,"Divergent Asymmetric Total Synthesis of (+)-Vincadifformine, (−)-Quebrachamine, (+)-Aspidospermidine, (−)-Aspidospermine, (−)-Pyrifolidine, and Related Natural Products","A uniformly strategic total synthesis of Aspidosperma alkaloids (+)-vincadifformine, (-)-quebrachamine, (+)-aspidospermidine, (-)-aspidospermine, (-)-pyrifolidine, and nine others from efficiently constructed tricyclic ketone 13 is reported. Highlights of these divergent and practical syntheses include (i) stereoselective intermolecular [4 + 2] cycloaddition to establish a C-E ring with one all-carbon quaternary stereocenter (C-5) and two bridged contiguous cis-stereocenters (C-12 and C-19), (ii) a Pd/C-catalyzed hydrogenation/deprotection/amidation cascade process to assemble the D ring, and (iii) Fischer indolization to forge the A-B ring.",10.1021/acs.orglett.7b01292,2017-06-01,0.6171322752339544
Organic Letters,Total Synthesis of the Putative Structure of the Lupin Alkaloid Plumerinine,"[reaction: see text]. A stereocontrolled synthesis of quinolizidine 1, the reported structure of plumerinine, has been accomplished in 10 steps from 4-methoxypyridine. The key step is a highly facial selective intramolecular [2 + 2] photocycloaddition of a 2,3-dihydro-4-pyridone. The reported spectral data for plumerinine did not match that of our synthetic 1.",10.1021/ol025820q,2002-03-26,0.6171280134133266
Organic Process Research & Development,"Lipase Catalyzed Regioselective Lactamization as a Key Step in the Synthesis of <i>N</i>-Boc (2<i>R</i>)-1,4-Oxazepane-2-Carboxylic Acid","A synthesis of N -Boc (2 R )-1,4-oxazepane-2-carboxylic acid 1 has been developed in 39% yield over seven steps starting from methyl (2 R )-glycidate 2 . The key step was a lipase-catalyzed regioselective lactamization of amino diester 5 into seven-membered lactam 6 . The transformation was performed using SpinChem rotating flow cell technology which simplified the work up and the recycling of the enzyme. Subsequent N -Boc protection followed by chemoselective borane reduction of the lactam moiety afforded 4- tert -butyl 2-methyl (2 R )-1,4-oxazepane-2,4-dicarboxylate 8 . Finally, hydrolysis mediated by LiBr/Et 3 N in wet acetonitrile yielded the title compound (2 R )-4-( tert -butoxycarbonyl)-1,4-oxazepane-2-carboxylic acid 1 .",10.1021/op5001644,2014-09-09,0.6171258138848015
European Journal of Organic Chemistry,Synthesis of Rare‐Bacterial Sugar Analogs: Thomosamine and Fluorinated Thomosamine,"Bacterial carbohydrates that include unusual deoxy amino sugars represent interesting targets in drug discovery. The chemical synthesis of such probes and fluorinated analogs is a challenge that needs to be addressed. In this work, a novel approach to thomosamine (4‐amino‐4,6‐dideoxy‐ d ‐galactopyranose ( d ‐Fuc p 4N)) and fluorinated thomosamines from levoglucosan (1,6‐anhydro‐ β ‐ d ‐glucopyranose) is developed. The key steps involve the introduction of the C4 amino on 1,6‐anhydro bridged intermediates and the subsequent C6 reduction. Thomosamine, 3‐deoxy‐3‐fluoro‐thomosamine, and 2,3‐dideoxy‐2,3‐difluoro‐thomosamine are accessed as their protected form with a thiophenyl group at the anomeric position.",10.1002/ejoc.202500523,2025-07-20,0.6171208288966387
European Journal of Organic Chemistry,Total Synthesis of the Cytotoxic Guaipyridine Sesquiterpene Alkaloid (+)‐Cananodine,"Abstract The enantiospecific total synthesis of the cytotoxic guaipyridine sesquiterpene alkaloid (+)‐cananodine ( 1 ) is described. A chiral pool/chiral auxiliary based approach is described for the synthesis of a key oxazolidinone intermediate. Subsequent key steps involve diastereoselective oxazolidinone allylation, cycloheptenylmethanol formation using ring‐closing olefin metathesis, microwave‐assisted decarboxylative Claisen rearrangement reaction, and use of a novel pyridine‐forming method.(© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2006)",10.1002/ejoc.200600414,2006-08-01,0.6171186818426434
Tetrahedron,Synthesis of (+)-laurencin via ring expansion of a C-glycoside derivative,,10.1016/j.tetlet.2005.08.024,2005-08-26,0.6171074793407008
Organic Letters,Formal Total Synthesis of the Cytotoxic Marine Ascidian Alkaloid Haouamine A,"[reaction: see text] Described is a convergent 13-step synthesis of a pentacyclic compound which has previously been transformed into haouamine A, therefore constituting a formal total synthesis of this unique marine alkaloid.",10.1021/ol060556c,2006-04-25,0.6171062394599462
Synthesis,Concise Synthesis of Diborylxanthenes,A simple and efficient synthesis of a series of bidentate diborylxanthene derivatives is described.,10.1055/s-2008-1032207,2008-03-01,0.6171009395804987
Journal of the American Chemical Society,"Total Synthesis of FR901464, an Antitumor Agent that Regulates the Transcription of Oncogenes and Tumor Suppressor Genes","FR901464 is a potent anticancer agent that regulates the transcription of oncogenes and tumor suppressor genes. A convergent enantioselective synthesis of FR901464 was accomplished in 13 linear steps. Central to the synthetic approach was the diene-ene cross olefin metathesis reaction to generate the C6-C7 olefin, without the use of protecting groups, as the final coupling. Additional key reactions include a Zr/Ag-promoted alkynylation to set the C4 stereocenter, a mild and chemoselective Red-Al reduction, a stereoselective Mislow-Evans-type [2,3]-sigmatropic rearrangement to install the C5 stereocenter, a Carreira asymmetric alkynylation to generate the C4' stereocenter, and a highly efficient ring-closing metathesis-allylic oxidation sequence to form an unsaturated lactone.",10.1021/ja058216u,2006-02-11,0.6170913223653249
Chemical Science,"Palladium catalyzed synthesis of indolizines <i>via</i> the carbonylative coupling of bromopyridines, imines and alkynes","the carbonylative formation of a high energy, mesoionic pyridine-based 1,3-dipole, which can undergo spontaneous cycloaddition with alkynes. Overall, this provides a route to prepare indolizines in a modular fashion from combinations of commercially available or easily generated reagents: 2-bromopyridines, imines and alkynes.",10.1039/d0sc03977b,2020-12-22,0.6170767602671728
Journal of Organic Chemistry,Synthesis of 2′-<i>C</i>-β-Methyl-2′-deoxyguanosine,"We describe two approaches for the synthesis of 2'-C-beta-methyl-2'-deoxyguanosine (3) via 2'-radical deoxygenation. One approach starts from 1,3,5-tri-O-benzoyl-alpha-d-ribofuranose (6) and gives 3 in 11 steps with 9.7% overall yield. The second approach starts from guanosine and gives 3 in 8 steps with 23% overall yield.",10.1021/jo802666k,2009-01-27,0.6170743164707568
Tetrahedron,A novel synthetic strategy for the stereospecific total synthesis of (±)-biotin,,10.1016/j.tetlet.2010.05.035,2010-06-01,0.6170675120736163
Tetrahedron,An efficient synthesis of 2-hydroxy-gibberellins,,10.1016/s0040-4039(00)84191-x,1986-01-01,0.6170667809714367
Tetrahedron,An efficient synthesis of 2-hydroxy-gibberellins,,10.1016/s0040-4039(86)80062-4,1986-01-01,0.6170667809714367
Organic Process Research & Development,Streamlined Synthesis of SHP2 Inhibitor GDC-1971 Enhanced by a Telescoped Schotten-Baumann S<sub><i>N</i></sub>Ar and Reactive Crystallization Cascade,"An improved synthetic process for SHP2 inhibitor GDC-1971 ( migoprotafib ) was developed to address challenges associated with the scalability and robustness of a preliminary fit-for-purpose route. In the optimized four-step sequence, the target’s pyrazolopyrazine core was functionalized sequentially, starting with an efficient palladium-catalyzed C–N coupling of its iodide with 1,2,3,4-tetrahydro-1,5-naphthyridine. Next, a nucleophilic aromatic substitution by a chiral aminospiropiperidine fragment upon the chloropyrazine was conducted under safe, biphasic Schotten-Baumann conditions and with high enough chemoselectivity that the product could be telescoped to a subsequent protecting group removal step. Isolation of the intermediate GDC-1971 hydrochloride salt leveraged reactive crystallization, whereas crystallization of the final GDC-1971 free base featured a wet milling operation to ensure a uniform particle size distribution. All of these improved reactions and revised workups/isolations were conducted on a multikilogram scale to provide a high-quality product without the need for chromatographic purification.",10.1021/acs.oprd.4c00162,2024-06-27,0.6170617099401554
Chemical Science,"Correction: Novel synthetic route for (parent) phosphetanes, phospholanes, phosphinanes and phosphepanes","Correction for ‘Novel synthetic route for (parent) phosphetanes, phospholanes, phosphinanes and phosphepanes’ by Stephan Reichl et al. , Chem. Sci. , 2023, 14 , 3834–3838, https://doi.org/10.1039/D3SC00580A.",10.1039/d3sc90080k,2023-01-01,0.6170598376858378
European Journal of Organic Chemistry,Total Synthesis of Aculenes B and D,"Abstract The first total synthesis of aculene D, a structurally rare nordaucane‐type natural product exhibiting quorum sensing inhibitory activity, has been accomplished from a known five‐membered hydroxy carboxylic acid. Nucleophilic addition of methallylzinc bromide to a β‐keto aldehyde intermediate under Barbier conditions to install the secondary hydroxy group on the seven‐membered ring of aculene D gave the corresponding alcohol with an undesired configuration predominantly. On the other hand, the protection of its keto group as the ethylene acetal induced a reversal of diastereoselectivity, affording a desired diastereomer in a selective manner. The construction of the seven‐membered ring was realized by ring‐closing metathesis using a triethylsilyl‐protected monocyclic diene ester precursor. An additional five‐step manipulation on the cyclization product including the installation of an ethyl group on the five‐membered ring completed the synthesis of aculene D, whose esterification with an N ‐protected l ‐proline followed by deprotection also achieved the first total synthesis of aculene B.",10.1002/ejoc.202201482,2022-12-23,0.6170592737359665
Organic Process Research & Development,The Synthesis of a GH-Releasing Compound NNC 26-1089,"The synthesis of trimethylhydrazine hydrochloride provides a stable and safe-to-handle reactant for multigram-scale synthesis making the preparation of the tripeptidelike Novo Nordisk growth hormone secretagogue NNC 26-1089 in multigram scale feasible. NNC 26-1089 was synthesised over seven steps in an overall yield of 33%, with a stereoisomeric purity of more than 99% measured by chiral capillary electrophoresis (CE).",10.1021/op0200118,2002-06-06,0.6170558709699832
Journal of Organic Chemistry,Total Synthesis of (−)-Macrocarpal C. Stereoselective Coupling Reaction with a Novel Hexasubstituted Benzene Cr(CO) <sub>3</sub> Complex as a Biomimetic Chiral Benzyl Cation Equivalent,"The first total synthesis of (−)-macrocarpal C ( 3 ) is described. The synthesis features a highly stereoselective coupling reaction of silyldienol ether 6 with biomimetic benzyl cation species ( R )- and ( S )- B, which were generated from novel hexasubstituted benzene chromium tricarbonyl complexes ( R )- and ( S )- 17 . At the final step of the total synthesis, we developed the tris- O -demethylation of macrocarpal C trimethyl ether 34 under basic conditions using lithium p -thiocresolate. Moreover, spectroscopic evidence shows that the synthetic (−)- 3 is identical to natural macrocarpal G ( 4 ).",10.1021/jo981413+,1998-12-01,0.6170550196430848
Journal of the American Chemical Society,Tandem [4 + 2]/[3 + 2] Cycloadditions of Nitroalkenes. 11. The Synthesis of (+)-Crotanecine,"(+)-Crotanecine ( 1 ) is the necine base component of a number of pyrrolizidine alkaloids. This necine subunit is an amino triol bearing a primary allylic alcohol characterized by an all-cis relationship of its stereocenters. The synthesis of (+)-crotanecine has been accomplished in 10 steps and 10.2% overall yield. The key step in the asymmetric synthesis is a Lewis acid-promoted, tandem inter[4 + 2]/intra[3 + 2] cycloaddition between a (fumaroyloxy)nitroalkene 14 and chiral β-silylvinyl ether (−)- 26 . This synthesis serves to illustrate the synthetic versatility of the tandem cycloaddition to incorporate additional functionality.",10.1021/ja963084d,1997-01-01,0.6170469470623078
Tetrahedron,"1,4-Cycloaddition of 1,3-diazabutadienes with enamines: An efficient route to the pyrimidine ring",,10.1016/s0040-4039(01)80748-6,1989-01-01,0.6170467554512861
Synthesis,"Synthesis of 2-Aryl(Heteroaryl)-9-oxo-1,9-dihydropyrrolo[3,2-<i>b</i>] [1]benzopyrans; A Novel Ring System",,10.1055/s-1981-29401,1981-01-01,0.6170358490518854
Journal of Organic Chemistry,"Practical, Catalytic, Asymmetric Synthesis of β-Lactones via a Sequential Ketene Dimerization/Hydrogenation Process:  Inhibitors of the Thioesterase Domain of Fatty Acid Synthase","The recent finding that the FDA-approved antiobesity agent orlistat (tetrahydrolipstatin, Xenical) is a potent inhibitor of the thioesterase domain of fatty acid synthase (FAS) led us to develop a concise and practical asymmetric route to pseudosymmetric 3,4-dialkyl-cis-beta-lactones. The well-documented up-regulation of FAS in cancer cells makes this enzyme complex an interesting therapeutic target for cancer. The described route to 3,4-dialkyl-beta-lactones is based on a two-step process involving Calter's catalytic, asymmetric ketene dimerization of acid chlorides followed by a facial-selective hydrogenation leading to cis-substituted-beta-lactones. Importantly, the ketene dimer intermediates were found to be stable to flash chromatography, enabling opportunities for subsequent transformations of these optically active, reactive intermediates. Subsequent alpha-epimerization and alpha-alkylation or acylation led to trans-beta-lactones and beta-lactones bearing alpha-quaternary carbons, respectively. Several of the ketene dimers and beta-lactones displayed antagonistic activity (apparent Ki in the low micromolar range) in competition with a fluorogenic substrate toward a recombinant form of the thioesterase domain of fatty acid synthase. The best antagonist, a simple phenyl-substituted cis-beta-lactone 3d, displayed an apparent Ki (2.5 +/- 0.5 microM) of only approximately 10-fold lower than that of orlistat (0.28 +/- 0.06 microM). In addition, mechanistic studies of the ketene dimerization process by ReactionView infrared spectroscopy support previous findings that ketene formation is rate determining.",10.1021/jo060392d,2006-05-18,0.6170304022663418
Organic Process Research & Development,Evolution of the Synthesis of AMPK Activators for the Treatment of Diabetic Nephropathy: From Three Preclinical Candidates to the Investigational New Drug PF-06409577,"Indole acids 1, 2, and 3 are potent 5′-adenosine monophosphate-activated protein kinase (AMPK) activators for the potential treatment of diabetic nephropathy. Compounds 1 – 3 were scaled to supply material for preclinical studies, and indole 3 was selected for advancement to first-in-human clinical trials and scaled to kilogram quantities. The progression of the synthesis strategy for these AMPK activators is described, as routes were selected for efficient structure–activity relationship generation and then improved for larger scales. The developed sequences employed practical isolations of intermediates and APIs, reproducible cross-coupling, hydrolysis, and other transformations, and enhanced safety and purity profiles and led to the production of 40–50 g of 1 and 2 and 2.4 kg of 3 . Multiple polymorphs of 3 were observed, and conditions for the reproducible formation of crystalline material suitable for clinical development were identified.",10.1021/acs.oprd.8b00059,2018-05-10,0.6170280308176137
Tetrahedron,Synthesis of (−)-(R)-angustureine by formal alkynylation of a chiral β-amino ester,,10.1016/j.tetlet.2012.12.122,2013-01-07,0.6170215479009196
Journal of Organic Chemistry,Formal Total Synthesis of Actinoranone: Synthesis Approaches and Cytotoxic Studies,"This article describes our efforts toward the total synthesis of actinoranone. Our synthesis strategies rely on a convergent route to connect the terpenoid and polyketide fragments, employing catalysis and powerful classical reactions for the assembly of these key fragments. A new transformation was disclosed during this work, a domino ring-opening and esterification. Initial cytotoxic studies for the selected synthesis intermediates are also presented.",10.1021/acs.joc.8b00514,2018-04-12,0.6170139000538076
European Journal of Organic Chemistry,Complex Structures of Antennary Human Milk Oligosaccharides − Synthesis of a Branched Octasaccharide,"We have developed a highly convergent synthetic route for the synthesis of the branched structure of human milk octasaccharide β-D-galactopyranosyl-(1→3)-2-acetamido-2-de oxy-β-D-glucopyranosyl-(1→3)-β-D-galactopyranosyl)-(1→4)-2-acetamido-2-deoxy-β-D-glucopyranosyl-(1→6)-[β-D-galactopyranosyl-(1→3)-2-acetamido-2-deoxy-β-D-glucopyranosyl-(1→3)]-β-D-galactopyranosyl-(1→4)-α,β-Dglucopyranose (1). In the retrosynthetic analysis, target structure 1 was disconnected into building blocks 2−6. Starting from only four known building blocks − 4, 7, 8, and 12 − the required three disaccharide units were obtained, resulting after further protecting group manipulation and glycoside bond formation in the desired tetrasaccharides 13 and 16. Cleavage of the TBDMS group of 13 afforded tetrasaccharide 14, which was transformed into isolactosamine-β-(1→3)-lactosamine trichloroacetimidate 15. Removal of the 4b,6b-O-benzylidene group of tetrasaccharide 16 gave the lacto-N-tetraose acceptor 17, to afford the protected octasaccharide 18 on glycosylation with donor 15. Complete deprotection of the octasaccharide by way of 19 afforded target human milk oligosaccharide 1 in a short and efficient route.",10.1002/1099-0690(200111)2001:22<4239::aid-ejoc4239>3.0.co;2-m,2001-11-01,0.617005356084964
Organic Letters,"Expedient Synthesis of Potent Cannabinoid Receptor Agonist (−)-CP55,940","[reaction: see text] A stereocontrolled synthesis of (-)-CP55,940, a potent cannabinoid receptor agonist, has been attained using a novel aldolization/retro-aldolization interconversion strategy, in which a temporarily generated chiral aldol motif plays essential roles.",10.1021/ol051570c,2005-08-18,0.6169940485346168
Angewandte Chemie International Edition,Total Synthesis and Antitumor Activity of ZK‐EPO: The First Fully Synthetic Epothilone in Clinical Development,"Going to trial: From about 350 active epothilone analogues synthesized by a highly convergent synthesis, one (ZK-EPO, see picture) has been chosen for clinical development on the basis of its outstanding preclinical data. This compound exhibits higher activity and efficacy than taxanes (e.g. paclitaxel) and second-generation epothilones, a fast and efficient cellular uptake, no recognition by efflux mechanisms, and an improved therapeutic window.",10.1002/anie.200602785,2006-09-27,0.6169860731091761
Tetrahedron,Synthesis of N-benzothiazol-2-yl-amides by a copper-catalyzed intramolecular cyclization process,,10.1016/j.tetlet.2007.11.100,2007-11-26,0.616976407528002
Journal of Organic Chemistry,Synthesis of (±)-7-Hydroxylycopodine,"A seven-step synthesis of (±)-7-hydroxylycopodine that proceeds in 5% overall yield has been achieved. The key step is a Prins reaction in 60% sulfuric acid that gave the key tricyclic intermediate with complete control of the ring fusion stereochemistry. A one-pot procedure orthogonally protected the primary alcohol as an acetate and the tertiary alcohol as a methylthiomethyl ether. The resulting product was converted to 7-hydroxydehydrolycopodine by heating with KO-t-Bu and benzophenone in benzene followed by acidic workup. During unsuccessful attempts to make optically pure starting material, we observed the selective Pt-catalyzed hydrogenation of the 5-phenyl group of a 4,5-diphenyloxazolidine under acidic conditions and the Pt-catalyzed isomerization of the oxazolidine to an amide under neutral conditions. In attempts to hydroxylate the starting material so that we could adapt this synthesis to the preparation of (±)-7,8-dihydroxylycopodine (sauroine) we observed the novel oxidation of a bicyclic vinylogous amide to a keto pyridine with Mn(OAc)(3) and to an amino phenol with KHMDS and oxygen.",10.1021/jo300353t,2012-03-24,0.616973524178521
Synthesis,Asymmetric Synthesis of α-Phenyl-γ-Hetero-Substituted Isopropyl Sulfonates via Diastereoselective Ring-Opening of γ-Sultones,"An efficient route to α-phenyl-γ-hetero (O, S, Se, Cl)-substituted isopropyl sulfonates via SN2-ring opening of γ-sultones, easily available by asymmetric synthesis from chiral lithiated sulfonates, is described. The title compounds are obtained in very good overall yields of 65-86% over three steps and excellent diastereo- and enantiomeric excesses (de = 94-96%, ee ≥ 98%).",10.1055/s-2007-983719,2007-06-01,0.6169725918063498
Tetrahedron,A convergent enantiocontrolled route to mevalonolactone and vitamin E from (S)-O-benzylglycidol,,10.1016/s0040-4039(00)94459-9,1990-01-01,0.616955073865714
Journal of Organic Chemistry,Enantioselective Model Synthesis and Progress toward the Putative Structure of Yuremamine,"An enantioselective model synthesis of the 2,3-dihydro-1H-pyrrolo[1,2-a]indole core of the putative structure of yuremamine is reported in 39% overall yield and 96% ee over five steps. The model synthesis leverages enantioselective, rhodium-catalyzed hydroacylation of an N-vinylindole-2-carboxaldehyde as the key step in the installation of the stereochemical triad. An enantioselective synthesis of a densely functionalized dihydropyrroloindolone that maps onto the putative structure of yuremamine is demonstrated in 26% yield and 97% ee over eight steps.",10.1021/acs.joc.6b01730,2016-08-05,0.616951875779826
Organic Letters,Five-Step Synthesis of Yaequinolones J1 and J2,"A concise synthesis of yaequinolones J1 and J2 is reported. The route is based on the aryne insertion into the σ-C–N bond of an unsymmetric imide followed by a diastereoselective aldol cyclization of the resulting N -acylated aminobenzophenone. The chromene motif is generated in the first step by an organocatalytic tandem Knoevenagel electrocyclization of citral and 2-bromoresorcinol. The approach adheres to the ideality principle, using almost exclusively strategic bond-forming reactions.",10.1021/acs.orglett.9b04455,2020-01-07,0.6169279200541329
European Journal of Organic Chemistry,Stereoselective Synthesis of 2‐Oxyenamides**,"Abstract An improved route for the highly stereoselective synthesis of ( Z )‐2‐oxyenamides is reported. The desired products can be accessed in only three steps from aminoacetaldehyde dimethyl acetal as common, readily available building block in a highly modular fashion. The improved procedure has been applied to the synthesis of various acylated and sufonylated oxyenamides. Mechanistic and theoretical studies provide a conclusive rationale for the observed stereoselectivities.",10.1002/ejoc.202200772,2022-07-18,0.6169245273267451
Journal of Organic Chemistry,Total Synthesis of Clavilactones,"Clavilactones A, B, and D are epidermal growth factor receptor tyrosine kinase inhibitors that were isolated from cultures of the fungus Clitocybe clavipes. Here, we report full details of the total synthesis of these clavilactones. A key feature of our synthetic approach is a ring-opening/ring-closing metathesis strategy that allows the concise transformation of a cyclobutenecarboxylate into a γ-butenolide. Coupled with enantioselective Ti/BINOL-catalyzed alkynylation of a multisubstituted benzaldehyde and ring-closing metathesis of a diene-bearing silylene acetal to construct the 10-membered carbocycle, this strategy enabled the total synthesis of the natural enantiomers (+)-clavilactone A and (-)-clavilactone B. In addition, the correct structure of clavilactone D was determined by the synthesis of two newly proposed structures. This research resulted in the asymmetric synthesis of the revised (+)-clavilactone D.",10.1021/acs.joc.7b03268,2018-01-31,0.6169040560687644
Tetrahedron,Concise and highly selective asymmetric synthesis of acosamine from sorbic acid,,10.1016/j.tetlet.2010.12.035,2010-12-23,0.616898034052265
Organic Letters,Asymmetric Synthesis of Vitamin D<sub>3</sub> Analogues: Organocatalytic Desymmetrization Approach toward the A-Ring Precursor of Calcifediol,A novel asymmetric synthesis has been developed for the construction of the A-ring of a chiral precursor to calcifediol. The highlights of this synthesis include (i) the introduction of the stereochemistry at the C5-position of the A-ring through the organocatalytic enantioselective desymmetrization of a prochiral cyclic anhydride using a bifunctional urea catalyst and (ii) the introduction of the exo-cyclic (Z)-dienol side chain by a tandem Claisen rearrangement/sulfoxide thermolysis of an allylic alcohol.,10.1021/acs.orglett.5b02813,2015-10-28,0.6168854257661852
Tetrahedron,Synthesis of 1-(2′- O -methyl-β- d -ribofuranosyl)-5-nitroindole and its phosphoramidite derivative,,10.1016/j.tetlet.2004.05.116,2004-06-16,0.6168769421142803
Journal of the American Chemical Society,Synthesis of Naturally Occurring Antitumor Agents:  Stereocontrolled Synthesis of the Azabicyclic Ring System of the Azinomycins,"Full details of the synthesis of the fully elaborated aziridino[1,2- a ]pyrrolidine substructure 2 of the antitumor agents azinomycins A and B are reported. Stereoselective bromination of dehydroamino acid 4 provided control of olefin configuration in the final product, as a consequence of a stereospecific cyclization of aziridine 3 onto the proximal β-bromoacrylate, which effected pyrrolidine ring introduction. Dehydroamino acid 4 was constructed by olefination of aldehyde 5 with a glycine-based phosphonate. Two complementary synthetic routes to 2 are presented. In the first route, the selectively protected C12/C13 diol system of the targets was introduced into starting structure 6 in a stereocontrolled manner using Brown's (γ-alkoxyallyl)diisopinocampheylborane reagent system. Transient protection of the C12 hydroxyl group of 48 as the trimethylsilyl ether was used to prevent C13 acetate migration prior to cyclization. Deprotection of the C12 hydroxyl following cyclization to the azabicyclic system afforded the extremely unstable core substructure 44, which could not be isolated, but was characterized in situ. In the second route, the racemic γ-alkoxystannane 8 was added in a chelation-controlled manner to serinal derivative 9 under conditions of kinetic resolution for introduction of the C12 and C13 stereogenic centers of the target. Phenylacetate and methoxyacetate esters were used for C12 hydroxyl protection. This work represents the first synthesis of the intact core substructure 44 of this novel class of natural products.",10.1021/ja992274w,1999-09-15,0.6168715719860131
Journal of Organic Chemistry,"A Scalable, Nonenzymatic Synthesis of Highly Stereopure Difunctional C<sub>4</sub> Secondary Methyl Linchpin Synthons","In response to the continuing widespread use of heterodifunctional C4 secondary methyl building blocks in asymmetric synthesis, we have developed a mole-scale, two-step synthesis of a 1:1 mixture of the diastereomers of 3-bromo-2-methyl-1-propyl camphorsulfonate (casylate). One isomer (2S) has been crystallized to >99:1 dr in ∼25% yield. Equilibration of the mother liquor (enriched in 2R) to a 1:1 mixture and recrystallization significantly raises the overall yield of 2S. Applications of 2S include chemoselective Grignard coupling, enabling the very short synthesis of highly stereopure long-chain natural products containing remote, methyl-bearing stereogenic centers [e.g., (R)-tuberculostearic acid], with complete control of configuration. Also, Ag-mediated, completely chemoselective Br displacement from 2S leads to a range of >99:1 er difunctional synthons. Both applications incorporate concurrent recovery of CasO. The enantiomer of 2S can be made from commercial (1R)-10-CasOH.",10.1021/jo5025392,2014-12-23,0.6168608788863231
Journal of the American Chemical Society,Annulative Methods Enable a Total Synthesis of the Complex Meroterpene Berkeleyone A,"Synthetic pathways to complex meroterpenes derived from 3,5-dimethylorsellinic acid (DMOA) and farnesyl pyrophosphate have not been reported despite heavy biosynthetic and medicinal interest. Herein we report the first total synthesis of berkeleyone A, a potential gateway compound to a plethora of fungal-derived meroterpenes, in 13 steps. In addition, we have further developed a novel annulation reaction for the synthesis of hydroxylated 1,3-cyclohexadiones in a single step.",10.1021/jacs.6b10397,2016-11-03,0.6168586156534863
Synthesis,"Synthesis of Marine Natural Product (2<i>S</i>,5<i>S</i>)-Pyrrolidine-2,5-dicarboxylic Acid","A five-step synthesis of marine natural product (2S,5S)-pyrrolidine-2,5-dicarboxylic acid (1) has been described starting from methyl ester of BOC-protected (S)-proline via stereoselective electrochemical oxidation with introduction of the methoxy group at C5-position by SN2-substitution of the cyano group followed by hydrolysis in 13% overall yield.",10.1055/s-2003-41075,2003-01-01,0.6168581671758482
Synthesis,Biocatalytic Asymmetric Synthesis of (<i>S</i>)- and (<i>R</i>)-Timolol,"A new biocatalytic route for the synthesis of both enantiomers of Timolol (1) is described. Starting from 3,4-dichloro-1,2,5-thiadiazole (2), (R)- and (S)-Timolol (87% ee) were obtained in 35% and 30% overall yield, respectively. Asymmetric reduction of the intermediate haloketone 5 with baker’s yeast afforded the corresponding halohydrin 6 in the optically active form (87% ee), which gave the R enantiomer (distomer) of Timolol. The S enan­tiomer (eutomer) was obtained via inversion of configuration of the halohydrin following the Mitsunobu procedure.",10.1055/s-2004-822395,2004-05-26,0.6168576881388939
Tetrahedron,An efficient synthetic route to substituted tetrahydropyrimidines by Cu(OTf)2-mediated nucleophilic ring-opening followed by the [4+2] cycloaddition of N-tosylazetidines with nitriles,,10.1016/j.tetlet.2008.12.035,2008-12-14,0.6168549569584728
Journal of the American Chemical Society,Tandem [4 + 2]/[3 + 2] Cycloadditions of Nitroalkenes. 9. Synthesis of (−)-Rosmarinecine,"(−)-Rosmarinecine ( 2 ) is the necine base portion of the pyrrolizidine alkaloid (−)-rosmarinine. (−)-Rosmarinecine is a representative of the group of pyrrolizidines that show a cis relationship between adjacent stereocenters C(1), C(7), and C(7a), in addition to a highly oxygenated skeleton. (−)-Rosmarinecine ( 2 ) has been synthesized in eight steps and 14.8% overall yield, as an illustration of a general approach for the construction of pyrrolizidines having this stereochemical feature. The key step in the asymmetric synthesis is a Lewis acid-promoted, tandem inter-[4 + 2]/intra-[3 + 2] cycloaddition between a fumaroyloxy nitroalkene and a chiral vinyl ether.",10.1021/ja961630x,1996-01-01,0.6168443807583024
Journal of Organic Chemistry,Iterative Synthetic Strategy for Azaphenalene Alkaloids. Total Synthesis of (−)-9a<i>epi</i>-Hippocasine,"A new strategy for the stereoselective synthesis of alkaloids with perhydro-9b-azaphenalene skeleton has been developed. The starting material is the substituted glutarimide derivative 1, readily available in either enantiomeric form through the palladium-catalyzed asymmetric allylic alkylation of glutarimide. The strategy relies on an iterative methodology encompassing two nucleophilic allylations and two ring closing metathesis processes. The approach has been used in the first synthesis of (-)-9a- epi-hippocasine.",10.1021/acs.joc.8b00390,2018-04-12,0.616843704532031
European Journal of Organic Chemistry,Total Synthesis of (+)‐Bourgeanic Acid Utilizing Desymmetrization Strategy,"Abstract A highly stereoselective total synthesis of an aliphatic depside (+)‐bourgeanic acid via (–)‐hemibourgeanic acid and bourgeanic lactone is described. The key steps involved in this synthesis are desymmetrization of bicyclic olefin with Brown's asymmetric hydroboration, Gillman's reaction, TEMPO‐BAIB mediated selective oxidation of 1,3‐diol, Yamaguchi macro‐lactonization and LiOH‐mediated partial hydrolysis of unusually stable eight‐membered cyclic dilactone.",10.1002/ejoc.201001199,2010-11-12,0.6168436743491872
Tetrahedron,Convergent synthesis of the ABCDE-ring fragment of the Caribbean ciguatoxin C-CTX-1,,10.1016/j.tetlet.2007.01.102,2007-01-25,0.6168365789278724
Tetrahedron,Convergent synthesis of the ABCDE ring fragment of ciguatoxins,,10.1016/j.tetlet.2004.04.083,2004-05-13,0.6168365789278724
Tetrahedron,Convergent synthesis of the EFGH ring fragment of ciguatoxin CTX3C,,10.1016/s0040-4039(01)01219-9,2001-08-01,0.6168365789278724
Tetrahedron,Convergent synthesis of the ABCDE ring fragment of ciguatoxins,,10.1016/s0040-4039(04)00873-1,2004-05-26,0.6168365789278724
Angewandte Chemie International Edition,Stereocontrolled Total Synthesis of (−)‐Aurisides A and B,"An expedient total synthesis of aurisides A and B (1), unusual cytotoxic macrolide glycosides isolated from the Japanese sea hare D. auricularia, takes advantage of a highly convergent aldol-based route for the stereocontrolled construction of the common macrolide core. This is followed by α-selective glycosylation to introduce the sugar moieties.",10.1002/anie.200462267,2005-01-21,0.616823046832534
Journal of Organic Chemistry,Studies on the Synthesis of Quartromicins A<sub>3</sub> and D<sub>3</sub>:  Synthesis of the Vertical and Horizontal Bis-Spirotetronate Fragments,"Syntheses of the vertical (3) and horizontal (4) bis-spirotetronate units of quartromicins A3 and D3 are described, along with an efficient synthesis of alpha-hydroxy aldehyde exo-8b, a precursor to the exo-spirotetronate fragments 19 and 21.",10.1021/jo061059c,2006-08-09,0.6168107800287554
European Journal of Organic Chemistry,Synthesis and Characterization of the Biologically Active 2-[1-(4-Chlorobenzyl)-1H-indol-3-yl]-2-oxo-N-pyridin-4-yl Acetamide,"The spectroscopic characterization of the new potent tubulin inhibitor 2-[1-(4-chlorobenzyl)-1H-indol-3-yl]-2-oxo-N-pyridin-4-yl acetamide (D-24851) (7), which is under preclinical development, is described. The synthesis was optimized and follows a straightforward route from the unsubstituted indole via the 1-(4-chlorobenzyl)-indole (3) and the indol-3-yl-2-oxo-acetyl chloride (5) to the indol-3-yl-2-oxo acetamide product. The structure was assigned by sophisticated NMR experiments, for example a 1,1-ADEQUATE experiment, and X-ray crystallography.",10.1002/1099-0690(200110)2001:20<3843::aid-ejoc3843>3.0.co;2-p,2001-10-01,0.616809552109921
Tetrahedron,A chiral amination reagent and an efficient synthesis of (S)-methyl -tolyl sulphoxide,,10.1016/s0040-4039(00)87432-8,1982-01-01,0.6168087770425688
Journal of the American Chemical Society,"Total Syntheses of the Telomerase Inhibitors Dictyodendrin B, C, and E","Concise and flexible total syntheses of the pyrrolo[2,3-c]carbazole alkaloids dictyodendrin B (2), C (3), and E (5) are described. These polycyclic telomerase inhibitors of marine origin derive from the common intermediate 18 which was prepared on a multigram scale by a sequence comprising a TosMIC cycloaddition with formation of the pyrrole A-ring, a titanium-induced reductive oxoamide coupling reaction to generate an adjacent indole nucleus, and a photochemical 6pi-electrocyclization/aromatization tandem to forge the pyrrolocarbazole core. Conversion of 18 into dictyodendrin C required selective manipulations of the lateral protecting groups and oxidation with peroxoimidic acid to form the vinylogous benzoquinone core of the target. Zinc-induced reductive cleavage of the trichloroethyl sulfate ester then completed the first total synthesis of 3. Its relatives 2 and 5 also originate from compound 18 by a selective bromination of the pyrrole entity followed by elaboration of the resulting bromide 27 via metal-halogen exchange or cross-coupling chemistry, respectively. Particularly noteworthy in this context is the generation of the very labile p-quinomethide motif of dictyodendrin E by a palladium-catalyzed benzyl cross-coupling reaction followed by vinylogous oxidation of the resulting product 41 with DDQ. The Suzuki step could only be achieved with the aid of the borate complex 40 formed in situ from p-methoxybenzylmagnesium chloride and 9-MeO-9-BBN, whereas alternative methods employing benzylic boronates, -trifluoroborates, or -stannanes met with failure.",10.1021/ja0617800,2006-05-24,0.6168055388584048
Synlett,Total Synthesis of Marine OxylipinsConstanolactone A and B,"A short, high-yielding synthesis of the marine oxylipins constanolactoneA and B was reported. Starting from cinnamyl alcohol (3), the cylopropyl lactone moiety 2 was obtained in 28% yield (11steps). The second coupling partner, vinyl iodide 1,was isolated in 7 steps and 32% yield. Chromium mediatedaddition yielded the natural products as a 2:1 mixture (74%).",10.1055/s-2003-40986,2003-01-01,0.616793019675426
Tetrahedron,Enantioselective total synthesis of the novel antiproliferative metabolite (+)-hexacyclinol,,10.1016/j.tetlet.2008.01.014,2008-01-09,0.6167832349064414
Tetrahedron,Synthesis of the spore photoproduct,The spore photoproduct was synthesized in seven steps from dihydrothymine and 5-formyluracil using a mixed Aldol coupling as the key bond forming step.,10.1016/s0040-4039(96)02517-8,1997-02-01,0.6167828172114218
Tetrahedron,Base-catalyzed cyclization of monofluorodienynes: a new route to substituted fluorobenzene derivatives,,10.1016/j.tetlet.2006.10.100,2006-11-16,0.6167787939665026
Tetrahedron,"26-Aminocholestanol derivative, a novel key intermediate of steroidal alkaloids, from Solanum abutiloides",,10.1016/0040-4039(95)01817-2,1995-11-01,0.6167775756157001
Synlett,Synthesis of the C19-C34 Segment of Amphidinolide C,"The synthesis of the C19-C34 segment of amphidinolide C is described. The key steps include the Mioskowski's Lewis acid catalyzed epoxide opening with the alcohol, ring-closing metathesis, Wittig reaction, and Nozaki-Hiyama-Kishi coupling reaction.",10.1055/s-2007-967968,2007-02-21,0.6167748374169222
European Journal of Organic Chemistry,A Concise Total Synthesis of the Non‐peptide Bradykinin B1 Receptor Antagonist Velutinol A,"Abstract A concise route to the bradykinin B1 receptor antagonist velutinol A, a natural product isolated from the rhizomatous of mandevilla velutina (Apocynaceae), has been developed. This synthesis features the highly regioselective construction of Δ 14 silyl enol ether 13 from diol 8a followed by stereoselective introduction of a sterically hindered β‐hydroxy group at the C14 position by Rubottom oxidation. A prolonged reaction time and the presence of an excess amount of m CPBA during this step allowed the double Rubottom oxidation to proceed through intermediate 16 to install β‐hydroxy groups at the C14 and C16 positions in one pot. The following conversions from α‐keto‐diol 18 to the target natural product were accomplished by reduction of the ketone at C15, oxidative cleavage of the C15–16 bond, and subsequent deprotection and intramolecular acetalization.",10.1002/ejoc.201101728,2011-12-28,0.616771977888855
Tetrahedron,Studies towards the total synthesis of methyl isosartortuoate: enantioselective synthesis of a precursor of the macrocycle,,10.1016/s0040-4039(00)00607-9,2000-06-01,0.616767654680589
Organic Process Research & Development,"An Efficient One-Pot Process for 10-Bromo-8-chloro-5,6-dihydro-benzo[5,6]cyclohepta[1,2-<i>b</i>]pyridin-11-one, an Intermediate to SCH 66336","An efficient process for the preparation of 10-bromo-8-chloro-5,6-dihydro-benzo[5,6]cyclohepta[1,2- b ]pyridin-11-one ( 7), an intermediate to an antitumor agent SCH 66336, is described. This one-pot method consists of a selective reduction of 8-chloro-7(9)-nitro-5,6-dihydro-benzo[5,6]cyclohepta[1,2- b ]pyridin-11-one ( 4 ) with Sn(II) bromide (generated in situ from Sn(II) sulfate and HBr), followed by bromination at the 10 position, and deamination. The desired product ( 7 ) is isolated in 75% overall yield.",10.1021/op034054f,2003-08-12,0.6167655741662068
Organic Letters,Asymmetric Synthesis of Heterocyclic Analogues of a CGRP Receptor Antagonist for Treating Migraine,"An asymmetric synthesis of novel heterocyclic analogue of the CGRP receptor antagonist rimegepant (BMS-927711, 3) is reported. The cycloheptane ring was constructed by an intramolecular Heck reaction. The application of Hayashi-Miyaura and Ellman reactions furnished the aryl and the amine chiral centers, while the separable diastereomeric third chiral center alcohols led to both carbamate and urea analogues. This synthetic approach was applicable to both 6- and 5-membered heterocycles as exemplified by pyrazine and thiazole derivatives.",10.1021/acs.orglett.5b02921,2015-12-09,0.6167426878913945
Tetrahedron,Divergent synthesis of cytotoxic styryl lactones isolated from Polyalthia crassa. The first total synthesis of crassalactone B,,10.1016/j.tetlet.2010.04.114,2010-05-01,0.6167280551850663
Synthesis,Short Synthesis of Dopamine Agonist Rotigotine,"Abstract A practical and short synthesis of FDA approved drug, Rotigotine, is achieved in two steps from 5-methoxy-2-tetralone, which in turn was synthesised by [4+2] cycloaddition of the in situ generated methoxyaryne from its precursor aryl triflate with benzyloxybutadiene or from 4-methoxyindanone via ring expansion using trimethylsilyldiazomethane.",10.1055/a-2235-5080,2023-12-27,0.6167218580154136
Tetrahedron,"Development of a synthetic route towards N4,N9-disubstituted 4,9-diaminoacridines: On the way to multi-stage antimalarials",,10.1016/j.tetlet.2019.03.052,2019-03-21,0.6166793986980862
Tetrahedron,A convergent carbohydrate approach to the synthesis of taxol. Part 2. Ring C subunit,,10.1016/0040-4039(95)00272-e,1995-04-01,0.6166765384247783
Tetrahedron,A convergent carbohydrate approach to the synthesis of taxol. Part 1. Ring A subunit,,10.1016/0040-4039(95)00271-d,1995-04-01,0.6166765384247783
Synlett,Asymmetric Total Synthesis of (+)-7-Deoxypancratistatin,"All articles of this category An asymmetric synthesis of 7-deoxypancratistatin 1 has been accomplished starting from diol 2 via two pathways in overall yields of 2.6 and 3.0%, respectively. The key step involved the regioselective ring opening of tosylaziridine 3 or the new carbomethoxyaziridine 15 with a higher-order cuprate and the cyclization of urethane 11 . 3-Bromo-3,5-cyclohexadiene-1,2-diol - vinylaziridine - higher-order cuprate - Bischler-Napieralski cyclisation",10.1055/s-1995-5221,1995-11-01,0.6166713874388304
Organic Letters,Total Synthesis of (−)-Stemospironine,"[structure: see text]. A stereocontrolled total synthesis of the polycyclic Stemona alkaloid, (-)-stemospironine (1) has been achieved. Key transformations include the use of a Staudinger reaction leading to the aza-Wittig ring closure of the perhydroazepine system. Formation of the vicinal pyrrolidine butyrolactone is described via the stereoselective intramolecular capture of an intermediate aziridinium salt.",10.1021/ol016336a,2001-08-01,0.6166667627167582
Journal of Organic Chemistry,Oxidative Rearrangement of Indoles:  A New Approach to the EFHG-Tetracyclic Core of Diazonamide A,"A new approach to the ring EFHG-tetracyclic core fragment of the marine secondary metabolite diazonamide A is described. The route is based on the oxidative rearrangement of 3-arylindole-2-carboxylates. Thus, a range of 3-arylindole-2-carboxylates (3, 8) underwent rearrangement to the corresponding 3,3-disubstituted oxindoles (4, 9) with migration of the ester group upon treatment with tert-butyl hypochlorite followed by acid. The oxindoles 9 with a 3-[2-(4-methoxybenzyloxy)]phenyl substituent underwent cyclization to the tetracyclic aminals 11 following N-protection, reduction, and treatment with methanesulfonic anhydride. The methodology was applied to the tyrosine-indole derivative 17 to give the EFHG-tetracyclic core of diazonamide A.",10.1021/jo062627r,2007-03-17,0.6166597216052346
Tetrahedron,Highly enantioselective total synthesis of natural epoxydictymene. An alkoxy-directed cyclization route to highly strained trans-oxabicyclo[3.3.0]octanes,,10.1016/s0040-4039(96)02287-3,1997-01-01,0.6166531221523011
Journal of the American Chemical Society,A Convergent Approach to Cyclopeptide Alkaloids:  Total Synthesis of Sanjoinine G1,"A general strategy for the synthesis of cyclopeptide alkaloids containing an endocyclic aryl-alkyl ether bond has been developed featuring a key intramolecular S(N)Ar reaction. The importance of the N-terminal protective group in the realization of such a strategy is documented. From the appropriate amino acid constituents, the natural sanjoinine G1, a 14-membered para cyclophane, has been synthesized in seven steps with 21% overall yield.",10.1021/ja0170807,2002-01-01,0.6166523807647437
Organic Process Research & Development,Novel and Cost-Effective Manufacturing Process Development of Daprodustat,"Daprodustat is a hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor indicated for treating anemia in patients with chronic kidney disease (CKD). This study describes a novel, efficient, and robust kilogram-scale manufacturing process for daprodustat starting from commercially available malonic acid by implementing quality by design (QbD) principles. A novel synthetic approach was adopted for the synthesis of methyl (1,3-dicyclohexyl-6-hydroxy-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carbonyl)glycinate by avoiding the use of ethyl isocyanatoacetate and replacing it with methyl glycinate and CDI. To our delight, we achieved a throughput of 76% with over 99% purity for daprodustat, compared to the previously reported throughput of 52%. This approach has enabled us to develop a more environmentally friendly process for synthesizing daprodustat than the prior method.",10.1021/acs.oprd.5c00041,2025-03-11,0.6166386129875303
Journal of Organic Chemistry,"An Efficient Enantioselective Synthesis of the D1 Agonist (5a<i>R</i>,11b<i>S</i>)-4,5,5a,6,7,11b-Hexahydro-2-propyl-3-thia- 5-azacyclopenta[<i>c</i>]phenanthrene-9,10-diol (A-86929)","(5aR,11bS)-4,5,5a,6,7,11b-Hexahydro-2-propyl-3-thia-5-azacyclopenta[c]phenanthrene-9,10-diol (A-86929, 1), a potent selective dopamine D1 agonist, was synthesized enantioselectively from D-aspartic acid. Key features of the 10-step synthesis are the following: (1) there is no chromatography required; (2) formation of 15 occurs in >99% ee; (3) the electrophilic cyclization to provide the desired trans stereochemisry in 18 is achieved with no loss of enantiomeric integrity.",10.1021/jo970066l,1997-05-01,0.6166333500039546
Tetrahedron,"Photoinduced cyclization of 3β-acetoxy-C(14a)-homo-B-norlanosta-8(14a),9(11)-diene as a route towards B(9a)-homo-C-norlanostane derivatives",,10.1016/s0040-4039(01)91340-1,1981-01-01,0.6166322206508832
Tetrahedron,The enantiospecific synthesis of (-)-monomorine from L-glutamic ester,,10.1016/s0040-4039(00)76960-7,1994-07-01,0.6166303767409472
Tetrahedron,Synthesis of a phospholecarboxylic ester,,10.1016/s0040-4039(01)84306-9,1972-01-01,0.6166303767409472
Journal of Organic Chemistry,Formal Enantioselective Total Synthesis of Schulzeines A–C via Pd–Catalyzed Intramolecular Asymmetric Allylic Amination,"Formal enantioselective total synthesis of schulzeines A-C was accomplished, featuring highly efficient Pd-catalyzed asymmetric allylic amination using novel diphosphonite ligands (BOPs) to provide 1-vinyltetrahydroisoquinoline key intermediates, as well as Ru-catalyzed ring-closing metathesis reaction to construct the key tricyclic cores in enantiopure form with correct absolute configurations.",10.1021/jo2009615,2011-06-14,0.616629326537193
Tetrahedron,A chiral synthesis of D-homoserine and its application to the synthesis of nocardicin A,,10.1016/s0040-4039(01)91502-3,1978-01-01,0.6166212732210926
Journal of the American Chemical Society,Total Synthesis of a PSGL-1 Glycopeptide Analogue for Targeted Inhibition of P-Selectin,"The high affinity interaction between P-selectin glycoprotein ligand-1 (PSGL-1) and P-selectin is mediated by a multimotif glycosulfopeptide (GSP) recognition domain consisting of clustered tyrosine sulfates and a Core 2 O -glycan terminated with sialyl Lewis X (C2- O -sLe X ). These distinct GSP motifs are much more common than previously appreciated within a wide variety of functionally important domains involved in protein–protein interactions. However, despite the potential of GSPs to serve as tools for fundamental studies and prospects for drug discovery, their utility has been limited by the absence of chemical schemes for synthesis on scale. Herein, we report the total synthesis of GSnP-6, an analogue of the N-terminal domain of PSGL-1, and potent inhibitor of P-selectin. An efficient, scalable, hydrogenolysis-free synthesis of C2- O -sLe X -Thr-COOH was identified by both convergent and orthogonal one-pot assembly, which afforded this crucial building block, ready for direct use in solid phase peptide synthesis (SPPS). C2- O -sLe X -Thr-COOH was synthesized in 10 steps with an overall yield of 23% from the 4- O,5- N oxazolidinone thiosialoside donor. This synthesis represents an 80-fold improvement in reaction yield as compared to prior reports, achieving the first gram scale synthesis of SPPS ready C2- O -sLe X -Thr-COOH and enabling the scalable synthesis of GSnP-6 for preclinical evaluation. Significantly, we established that GSnP-6 displays dose-dependent inhibition of venous thrombosis in vivo and inhibits vaso-occlusive events in a human sickle cell disease equivalent microvasculature-on-a-chip system. The insights gained in formulating this design strategy can be broadly applied to the synthesis of a wide variety of biologically important oligosaccharides and O -glycan bearing glycopeptides.",10.1021/jacs.4c05090,2024-06-12,0.6166202843985801
Synthesis,First Total Synthesis of (–)-Auranomide C and Its Derivatives,The first total synthesis of (–)-auranomide C has been achieved. The short synthetic strategy involves a reductive dehydrocyclization and the nucleophilic ring opening of a fused γ-lactam. The route allows for ease in synthesizing diverse derivatives in the side chain of the natural product.,10.1055/s-0033-1338558,2013-11-14,0.6166109639985482
Synthesis,Efficient Asymmetric Syntheses of (+)-Strictifolione,"The asymmetric synthesis and a formal asymmetric synthesis of (+)-strictifolione are described. As key step in both approaches the Julia-Kocienski olefination to create an E-configured alkene was used. The anti-1,3-diol moiety was synthesized by employing a SAMP-hydrazone α,α′-bisalkylation/deoxygenation protocol and the stereocentre of the lactone unit is based on an enzymatic reduction with baker's yeast. Alternatively, a lactone precursor could be efficiently synthesized by a (S)-proline catalyzed α-oxyamination of pent-4-enal.",10.1055/s-2004-822387,2004-01-01,0.6165854528331843
Journal of Organic Chemistry,A Practical and Azide-Free Synthetic Approach to Oseltamivir from Diethyl <scp>d</scp>-Tartrate,"A short and practical synthesis of oseltamivir was accomplished in 11 steps from inexpensive and abundant diethyl D-tartrate starting material. This azide-free route featured an asymmetric aza-Henry reaction and a domino nitro-Michael/Horner-Wadsworth-Emmons (HWE) reaction as the key steps to construct the relevant cyclohexene ring of the product, which provided an economical and practical alternative for the synthesis of oseltamivir.",10.1021/jo100187m,2010-04-15,0.6165850405904851
Organic Letters,"Stereoselective and Efficient Synthesis of (3<i>R</i>,3a<i>S</i>,6a<i>R</i>)-Hexahydrofuro[2,3-<i>b</i>]furan-3-ol","[reaction: see text] Two short and efficient synthesis routes have been developed for bis-THF-alcohol 2, a key building block of the investigational HIV protease inhibitor TMC114 (1). Using S-2,3-O-isopropylideneglyceraldehyde (4) as the source of chirality, both routes are based on a diastereoselective Michael addition of nitromethane to give predominantly the syn congeners 6 followed by a Nef oxidation and cyclization to afford lactone acetals 8, which are reduced and cyclized to give 2.",10.1021/ol052554i,2005-12-01,0.6165828333746037
Synthesis,An Improved Procedure for the Preparation of the Garner Aldehyde and Its Use for the Synthesis of<i>N</i>-Protected 1-Halo-2-(<i>R</i>)-amino-3-butenes,"All articles of this category An improved procedure for the preparation of 1,1-dimethylethyl 2,2-dimethyl-4-( S )-formyloxazolidine-3-carboxylate (Garner aldehyde) is described which avoids the need for methyl iodide and benzene. Elaboration of this aldehyde into the novel chiral building blocks mentioned in the title is also described.",10.1055/s-1994-25398,1994-01-01,0.6165634709043192
Synthesis,"Synthesis of Optically Active 15-epi-9,14-Methylene Lipoxin A4","The synthesis of lipoxin A4 and B4 analogues (LXA4, LXB4) to gain access to stabilized inflammation resolving compounds is an important field of research. Starting from known structural requirements of the natural compounds displaying biological activity and a broad investigation of their rapid metabolism, various LXA4 derivatives have been developed and tested. Focusing on variation and stabilization of the conjugated E,E,Z,E C7–C14 tetraene moiety of natural LXA4, a methylene bridge introduced between C9 and C14 might suppress any Z/E isomerization of the C11–C12 olefin. Intending to enable at least known structure variations in connection with the C1–C7 and the C15–C20 fragments, a convergent total synthesis starting from a known cycloheptatriene is developed. The C1–C8 building blocks are generated via six-step ex-chiral pool sequences starting from 2-deoxy-d-ribose delivering two 5,6-dihydroxy carboxylic acid derivatives with C7 aldehyde functions. The synthesis of the C8–C21 building block starts from a known cycloheptatriene 1-carbonester (C8–C14, C21) and hexanoyl chloride (C15–C20). After Friedel–Crafts-type coupling, the defined configuration of the C15 OH group is introduced via enantioselective reduction of the ketone precursor. Following an additional four steps, an aryl sulfone C9–C21 building block is completed ready for a key Julia–Kocienski olefination with the C1–C7 compounds. Finally, removal of the protecting groups completes the synthesis of the target optically active 9,14-methylene LXA4 methyl ester.",10.1055/s-0036-1591899,2018-02-21,0.6165487197057087
Tetrahedron,"A new route to the bis-benzocyclooctadiene lignan skeleton: Total syntheses of (±) picrostegane, (±) isopicrostegane and (±) isostegane",,10.1016/s0040-4039(01)95009-9,1978-01-01,0.6165454843464769
Journal of Organic Chemistry,Total Synthesis of the Potent Marine-Derived Elastase Inhibitor Lyngbyastatin 7 and in Vitro Biological Evaluation in Model Systems for Pulmonary Diseases,"Lyngbyastatin 7 (1) is a marine cyanobacteria-derived lariat-type cyclic depsipeptide of which the macrocyclic core possesses modified amino acids, including a featured 3-amino-6-hydroxy-2-piperidone (Ahp) moiety and a (Z)-2-amino-2-butenoic acid (Abu) moiety. The first total synthesis of 1 was successfully established via 31 steps, and the conditions of several crucial steps were optimized to ensure smooth operations. The previously reported structural assignment and elastase inhibitory activity of the isolated natural product were confirmed. According to the extensive in vitro biological evaluation, compound 1 displayed low nanomolar IC50 in blocking elastase activity and strong ability in protecting bronchial epithelial cells against elastase-induced antiproliferation and abrogating the elastase-triggered induction of pro-inflammatory cytokine expression. Its overall performance was superior over sivelestat, the only approved small molecule drug targeting elastase, which indicated its potential in developing as a pharmacotherapeutic against elastase-mediated pathologies. The success in total synthesis, designed with a novel convergent strategy, not only overcame the supply issue for thorough preclinical studies but also paved the way for convenient synthesis of analogues with improved potency and druglike properties.",10.1021/acs.joc.5b02386,2015-12-28,0.616534712350582
Synthesis,Carbonylations of Alkenes in the Total Synthesis of Natural Compounds,"All articles of this category Correction to: Carbonylations of Alkenes in the Total Synthesis of Natural Compounds Synthesis 2016; 48(11): 1573-1596 DOI: 10.1055/s-0035-1560431 We regret that we unintentionally omitted to refer to the important pioneering work of James Leighton and his co-workers in our review. This group has substantially contributed both to the development of synthetic methodologies based on hydroformylation and to their application in the total synthesis of natural compounds. Therefore, we would like to add following sentences and references to the original manuscript: Page 1576, left column, second paragraph: the first sentences should be changed to: ‘An elegant approach to the synthesis of naturally occurring polyketides using catalytic C–C bond-forming reactions, including hydroformylation, was originally described by Leighton in 2011 and later by Krische and co-workers in the synthesis of (+)-zincophorin methyl ester ( 23 ). 20 The free acid of this compound is a highly potent antibiotic that was isolated from soil bacteria. 21 Krische’s retrosynthesis is based on the construction of fragments A ( 18 ) and B ( 22 ) and their highly diastereoselective connection at the late stage of the synthesis (Scheme 5).’ Accordingly, the reference 20 should be changed to: (20) (a) Harrison, T. J.; Ho, S.; Leighton, J. L. J. Am. Chem. Soc. 2011 , 133 , 7308. (b) Kasun, Z. A.; Gao, X.; Lipinski, R. M.; Krische, M. J. J. Am. Chem. Soc. 2015 , 137 , 8900. Page 1579, left column, the first paragraph should end with the following sentence: ‘Notably, Leighton et al. used ligand 54 in two enantioselective hydroformylation steps of an innovative step-economic (14 steps, longest linear sequence) total synthesis of dictyostatin. i ’ Reference i: Ho, S.; Bucher, C.; Leighton, J. L. Angew. Chem. Int. Ed. 2013 , 52 , 6757. Page 1584, right column, the last two sentences should be changed to: ‘Notably, the Rh-catalyzed tandem hydroformylation–lactol formation reaction was initially successfully applied in the first total synthesis of leucascandrolide A by Leighton and co-workers in 2000. 58 ’ The authors apologize for the mistakes. Synthesis 2016 , 48, 1573–1596 .",10.1055/s-0035-1562550,2016-08-03,0.616521121785085
Tetrahedron,Biomimetic total synthesis of colneleic acid and its function as a lipoxygenase inhibitor,,10.1016/s0040-4039(00)96658-9,1987-01-01,0.616519512782132
Tetrahedron,Towards the synthesis of osteoclast inhibitor SB-242784,,10.1016/s0040-4039(03)00544-6,2003-03-26,0.616505881124905
Tetrahedron,A concise synthesis of (±) and a total synthesis of (+)-epiquinamide,,10.1016/j.tetlet.2006.05.092,2006-06-15,0.6164984139882462
European Journal of Organic Chemistry,Optimized and Scalable Synthesis of Carba‐α‐<scp>d</scp>‐Glucosamine,"An efficient, high‐yielding synthesis of carba‐α‐ d ‐glucosamine is reported. Key features of this optimized route include an innovative protecting group strategy and an unusual, stereoconvergent Ferrier carbocyclization of a hindered substrate. The sequence enables the synthesis of larger amounts of this structurally novel antibiotic to allow more detailed biological evaluations of its unique mode of action.",10.1002/ejoc.202001203,2020-11-04,0.6164979303464636
Journal of Organic Chemistry,Efficient Access to 2-Aryl-3-Substituted Benzo[<i>b</i>]thiophenes,"[reaction: see text] Benzo[b]thiophene derivatives are important in part because of their use as selective estrogen receptor modulators. They are usually synthesized by intramolecular cyclization. Here, we propose a method for the synthesis of 2-arylbenzo[b]thiophenes with heteroatoms at the 3-positions directly from the benzo[b]thiophene core by using an aromatic nucleophilic substitution reaction and Heck-type coupling. This methodology provides 2-aryl-3-amino or phenoxybenzo[b]thiophenes in about 35% overall yield in 5 steps.",10.1021/jo0500378,2005-03-26,0.6164720982861963
Tetrahedron,Synthesis of 5-(9-adenyl)-4-ethyl-3-methyl-5(H)-furanone,,10.1016/s0040-4039(01)97797-4,1970-01-01,0.6164674326683705
European Journal of Organic Chemistry,Practical Syntheses of (2<i>S</i>)‐R207910 and (2<i>R</i>)‐R207910,"Abstract Concise and practical syntheses of (2 S )‐R207910 ( 3a ) and (2 R )‐R207910 ( 3b ) have been achieved in high overall yield of 12 % in 10 steps for each isomer starting from a known intermediate following Sharpless asymmetric epoxidation, regioselective epoxide opening, modified allylzinc bromide addition as key reactions.",10.1002/ejoc.201001720,2011-03-03,0.6164669845920631
Organic Process Research & Development,Development of a Manufacturing Route to 1-Hydroxy-4-(3-pyridyl)butan-2-one Using Heck Methodology,"The optimisation and scale-up of a manufacturing route to a key intermediate, 1-hydroxy-4-(3-pyridyl)butan-2-one, utilising the Heck coupling of 3-bromopyridine and 3-butene-1,2-diol, is described.",10.1021/op0255736,2002-10-10,0.6164632427469663
European Journal of Organic Chemistry,Asymmetric Synthesis of Trifluoromethylated <i>ent</i>‐Fragransin C<sub>1</sub>,"Asymmetric synthesis of trifluoromethylated derivative of ent ‐fragransin C 1 was reported. The installation of contiguous stereochemistries across the tetrahydrofuran scaffold was achieved through stereocontrolled conjugate addition, aldol reaction, and a protection‐free intramolecular C‐O bond formation (furan ring formation) via chemoselective generation of the benzylic carbocation.",10.1002/ejoc.201801676,2018-12-21,0.6164570154865031
Organic Process Research & Development,Process Development of a Novel Azetidinyl Ketolide Antibiotic,"Process development and the multikilogram synthesis of a novel azetidinyl ketolide antibiotic is described. Starting with clarithromycin, the eight-step synthesis features several telescoped operations and direct isolations, which results in a significant improvement in throughput and a major reduction in solvent usage and waste stream volume over the first scale-up campaign. Particular highlights of this effort include the development of an efficient synthesis of 3-hydroxy-1,5-naphthyridine-4-carbaldehyde via a Skraup process and engineering a robust final API synthesis. We also discovered a crystalline monotosylate salt that addressed significant formulation and degradation issues experienced when using the noncrystalline freebase.",10.1021/op300064b,2012-04-30,0.6164551417875628
Organic Letters,Pd-Catalyzed C–H Lactonization for Expedient Synthesis of Biaryl Lactones and Total Synthesis of Cannabinol,"A practical Pd(II)/Pd(IV)-catalyzed carboxyl-directed C-H activation/C-O cyclization to construct biaryl lactones has been developed. The synthetic utility of this new reaction was demonstrated in an atom-economical and operationally convenient total synthesis of the natural product cannabinol from commercially available starting materials, with the newly developed method used for two key steps.",10.1021/ol400877q,2013-05-10,0.6164487548516806
Synlett,Short and Efficient Synthesis of Cadiolide B,"The first synthesis of cadiolide B has been achieved in 6 steps and 42% overall yield from 4-bromo-2(5H)-furanone. The pathway involves sequential, regiocontrolled introduction of the three furanone substituents by means of aldol reactions and Suzuki cross coupling.",10.1055/s-2004-837220,2005-01-01,0.6164453352220831
Organic Process Research & Development,"Rapid Development of an Enantioselective Synthesis of (<i>R</i>)-1-Hydroxy-7-methoxy-1,2,3,4-tetrahydronaphthalene-1-carboxylic Acid","A two-stage, three-step synthesis of ( R )-1-hydroxy-7-methoxy-1,2,3,4-tetrahydronaphthalene-1-carboxylic acid from 7-methoxy tetralone is described which employed an optimised Wittig olefination of 7-methoxytetralone and Sharpless asymmetric dihydroxylation followed by platinum-catalysed oxidation.",10.1021/op025590v,2003-02-12,0.6164430487565752
Tetrahedron,A novel synthesis of an a-ring precursor to 1α-hydroxyvitamin D,,10.1016/s0040-4039(00)79355-5,1993-07-01,0.6164259745390765
Synlett,Enantioselective Synthesis of (+)-Ricciocarpin A Using an Auxiliary Hydroxyl Group and a Diastereofacial Selectivity Based Methodology,"An enantioselective synthesis of (+)-ricciocarpin A is described starting from (+)-karahana lactone as an enantiopure building block. This synthesis involves a stereofacially directed diastereoselective hydroboration for the installation of the required stereogenic center, and the efficient conversion of an intermediate hydroxyaldehyde to the one-carbon homologated cyanide, using the mild formation of a cyanohydrin followed by an one-pot two-step Barton-McCombie double deoxygenation sequence of the hydroxyl moieties.",10.1055/s-2005-871932,2005-01-01,0.6164186587811068
Organic Process Research & Development,"Scalable Non-Aqueous Process to Prepare Water Soluble 3-Amino-pentan-1,5-diol","The development of a nonaqueous process for the synthesis of 3-amino-pentan-1,5-diol is described. Beginning with dimethyl acetone-1,3-dicarboxylate, a telescoped sequence of reductive amination, Boc protection, sodium borohydride reduction, and acidic resin-mediated deprotection generates the title compound. The key to this efficient process is the telescoped deprotection, purification and nonaqueous isolation of the 3-amino-pentan-1,5-diol. The process involves four optimized chemical reactions using two solvents in 89% overall yield and 97−98 area % purity.",10.1021/op800245v,2009-02-13,0.6164054447156597
Reaction Chemistry & Engineering,Metal-free synthesis of an estetrol key intermediate under intensified continuous flow conditions,Development of a scalable and intensified thermolysis process for the preparation of a key intermediate toward estetrol.,10.1039/d3re00051f,2023-01-01,0.6164032918404075
Journal of Organic Chemistry,"Bioinspired Total Synthesis and Human Proteasome Inhibitory Activity of (−)-Salinosporamide A, (−)-Homosalinosporamide A, and Derivatives Obtained via Organonucleophile Promoted Bis-cyclizations","A full account of concise, enantioselective syntheses of the anticancer agent (-)-salinosporamide A and derivatives, including (-)-homosalinosporamide, that was inspired by biosynthetic considerations is described. The brevity of the synthetic strategy stems from a key bis-cyclization of a β-keto tertiary amide, which retains optical purity enabled by A(1,3)-strain rendering slow epimerization relative to the rate of bis-cyclization. Optimization studies of the key bis-cyclization, enabled through byproduct isolation and characterization, are described that ultimately allowed for a gram scale synthesis of a versatile bicyclic core structure with a high degree of stereoretention. An optimized procedure for zincate generation by the method of Knochel, generally useful for the synthesis of salino A derivatives, led to dramatic improvements in side-chain attachment and a novel diastereomer of salino A. The versatility of the described strategy is demonstrated by the synthesis of designed derivatives including (-)-homosalinosporamide A. Inhibition of the human 20S and 26S proteasome by these derivatives using an enzymatic assay are also reported. The described total synthesis of salino A raises interesting questions regarding how biosynthetic enzymes leading to the salinosporamides proceeding via optically active β-keto secondary amides, are able to maintain the stereochemical integrity at the labile C2 stereocenter or if a dynamic kinetic resolution is operative.",10.1021/jo101638r,2010-11-03,0.6163737458762847
Organic Process Research & Development,Practical Large-Scale Preparation of (±)-2-<i>exo</i>-Norbornyl Carboxylic Acid and Its Improved Isolation As the Sodium Salt,"A practical, robust, and high-yielding three-step−one-pot procedure for the diastereoselective synthesis of (±)-2- exo -norbornyl carboxylic acid starting from norbornylene has been found and demonstrated on multikilogram scale, setting a new benchmark for low-pressure hydroformylation of cyclic, bridged olefins. The newly found, nonhygroscopic crystalline sodium salt of this acid provides a practical isolation point.",10.1021/op100284a,2011-02-10,0.6163560060304504
Chemical Science,A catalytic asymmetric total synthesis of (−)-perophoramidine,"We report a catalytic asymmetric total synthesis of the ascidian natural product perophoramidine. The synthesis employs a molybdenum-catalyzed asymmetric allylic alkylation of an oxindole nucleophile and a monosubstituted allylic electrophile as a key asymmetric step. The enantioenriched oxindole product from this transformation contains vicinal quaternary and tertiary stereocenters, and is obtained in high yield along with high levels of regio-, diastereo-, and enantioselectivity. To install the second quaternary stereocenter in the target, the route utilizes a novel regio- and diastereoselective allylation of a cyclic imino ether to deliver an allylated imino ether product in near quantitative yield and with complete regio- and diastereocontrol. Oxidative cleavage and reductive amination are used as final steps to access the natural product.",10.1039/c4sc01826e,2014-07-31,0.6163555182800602
Synthesis,"A Novel Dieckmann-Type Cyclization, the Final Step of the Synthesis of a Carbacephem Derivative","All articles of this category The treatment of the triacylamine, methyl 4-(dibenzoylaminocarbonylethyl)-2-oxoazetidine-1-acetate ( 2 ), with sodium bis(trimethylsilyl)amide leads to an unprecedented Dieckmann-type ring closure to form the anion of the carbacephem derivative, methyl 3-hydroxy-1-carbacephem-4-carboxylate, ( 3 ).",10.1055/s-1991-26563,1991-01-01,0.6163455693159957
Tetrahedron,Synthetic approaches to the angucycline antibiotics: Synthesis of the C-glycosidic CD ring system,,10.1016/s0040-4039(00)78474-7,1994-11-01,0.6163384683521685
Journal of Organic Chemistry,"Regiochemically Pure 1,6-Ditriflato-Perylene Diimide: Preparation and Transformation","Preparation of regioisomerically pure 1,6-disubstituted perylene diimide (PDI) is not a trivial task owing to the lack of facile synthetic and separation methodologies for the precursors. Herein, we present a simple synthesis for 1,6-ditriflato-PDI ( 1,6-diOTf-PDI ) using 1,6,9,10-tetrabromo-perylene monoimide 1 as the starting material. The selective methoxylation of 1 at the 1,6-position is the key step. Based on a four-step sequence of selective methoxylation, domino carbonylative amidation, demethylation, and triflation, 1,6-diOTf-PDI can be obtained in a satisfactory yield. Moreover, as a building block, 1,6-diOTf-PDIa can readily undergo Suzuki and Sonogashira cross-coupling reactions.",10.1021/acs.joc.2c01246,2022-10-19,0.6163318602523233
Organic Process Research & Development,Bio- and Chemocatalysis for the Synthesis of Late Stage SAR-Enabling Intermediates for ROMK Inhibitors and MK-7145 for the Treatment of Hypertension and Heart Failure,"A synthetic strategy to provide two late-stage intermediates for the synthesis of diverse analogues of ROMK inhibitors for the treatment of hypertension and heart failure is described. Key transformations include carbonylation of a bromoarene, regioselective vinyl ether Heck coupling and bromination, and asymmetric enzyme-mediated ketone reduction and epoxide ring closure. On selection of MK-7145 ( 1 ) as clinical candidate, conditions were developed to convert 2 equiv of the epoxide intermediates to the C 2 -symmetric active pharmaceutical ingredient.",10.1021/acs.oprd.0c00314,2020-10-05,0.6163281728114326
European Journal of Organic Chemistry,"General Asymmetric Synthetic Strategy for the α‐Alkylated 2,5,6‐Trisubstituted Pyran of Indanomycin and Related Natural Products","A general synthetic strategy for convergent asymmetric synthesis of C1–C10 fragment of tetraene‐containing natural product indanomycin was achieved starting from 2‐(benzyloxy)acetaldehyde which in turn was obtained from very inexpensive material cis ‐1,4‐butene‐diol. Key steps include Evans' aldol reaction, HWE olefination, iodine‐catalyzed tandem isomerization followed by C–O and C–C bond formation similar to our earlier report in constructing the trans ‐2,6‐disubstituted dihydropyran ring and Evans' asymmetric alkylation.",10.1002/ejoc.202000156,2020-02-27,0.6163253599714362
Tetrahedron,A novel formation of (±)-glaziovine through nitrenium intermediate,,10.1016/s0040-4039(01)87153-7,1973-01-01,0.6163247464659197
Organic Letters,Total Synthesis of Spirobacillene A,"The first total synthesis of spirobacillene A, an indole alkaloid isolated from Lysinibacillus fusiformis, is reported. A Lewis acid mediated spirocyclization of an anisole derivative onto a tethered ynone was used as a key step, drawing inspiration from a potential biosynthesis of the natural product.",10.1021/ol4013958,2013-06-20,0.6163218127410826
Journal of Organic Chemistry,An Efficient Synthesis of (Fluoromethyl)pyridylamines for Labeling with Fluorine-18,"We have described a two-step method for the preparation of (fluoromethyl)pyridyl-substituted amines. The sequence involves fluoride ion displacement of methanesulfonates (mesylates) of 6-chloro-α-hydroxy-2- and -3-picolines, followed by arylation of the amine by chloropicoline. We have called this sequence fluorination− N -arylation. 1-Phenylpiperazine has been used as a model amine. Two key precursors for this sequence are the mesylates of 6-chloro-α-hydroxy-2- and -3-picolines. The former was synthesized in four steps from 6-chloro-2-picoline in 78% yield and the latter in three steps from 6-chloronicotinic acid in 53% yield. This fluorination− N -arylation sequence is sufficiently rapid and efficient for the preparation of a variety of aryl-substituted amine compounds labeled with the short half-life ( t 1/2 = 110 min) positron-emitting radionuclide fluorine-18.",10.1021/jo990994f,1999-11-01,0.6163085082199333
Green Chemistry,One-pot synthesis of chiral β-hydroxysulfones from alkynes <i>via</i> aerobic oxysulfonylation and asymmetric reduction in MeOH/H <sub>2</sub> O,A highly enantioselective synthesis of β-hydroxysulfones from inexpensive and readily available alkynes <italic>via</italic> a consecutive one-pot reaction in MeOH/H <sub>2</sub> O under mild conditions is described.,10.1039/c8gc03671c,2019-01-01,0.6163001710635647
Tetrahedron,A new route to spiroacetals and the construction of a model for the synthesis of phyllanthocin,,10.1016/s0040-4039(01)93438-0,1989-01-01,0.6162875938638671
Tetrahedron,Synthesis of an amphiphilic aldehyde using as a key step the condensation of a lipophilic glyoxylic acid amide derivative with tris(hydroxymethyl)aminomethane,,10.1016/s0040-4039(01)00032-6,2001-03-01,0.616276407070637
European Journal of Organic Chemistry,A Short Synthesis of Mniopetal F,"The first total synthesis of Mniopetal F in fourteen steps is reported. Key steps are a new and highly diastereoselective lithium phenylselenide-induced Baylis−Hillman reaction with Feringa′s butenolide, an endo-selective intramolecular Diels−Alder reaction (IMDA), inversion of a highly hindered secondary alcohol and a new variant of the Parikh−Doering oxidation.",10.1002/1099-0690(200102)2001:3<473::aid-ejoc473>3.0.co;2-j,2001-02-01,0.6162760493040006
Organic Letters,Synthesis of Sominone and Its Derivatives Based on an RCM Strategy: Discovery of A Novel Anti-Alzheimer’s Disease Medicine Candidate “Denosomin”,"Synthesis of sominone was achieved starting from dehydroepiandrosterone on the basis of an RCM strategy for the construction of a delta-lactone side chain. This synthetic protocol was applied for the synthesis of several analogous derivatives including 1-deoxy-24-norsominone (denosomin), which was revealed to exhibit notable bioactivities for new antidementia chemotherapy, exceeding the original natural compound sominone.",10.1021/ol901553w,2009-08-04,0.6162724139780658
Synthesis,Asymmetric Total Synthesis of Lobophopyranone A and B,"Abstract The first asymmetric total synthesis and structural confirmation of lobophopyranone A and B have been accomplished from commercially available starting materials. Reagent-controlled Keck–Maruoka allylation, Grignard reaction, chelation-controlled Sakurai allylation, and acid-mediated one-step TBS ether deprotection followed by cyclization are the crucial stages in this synthesis that create the 2,6-disubstituted dihydropyranone component.",10.1055/a-2338-4462,2024-06-04,0.6162652246876597
Journal of the American Chemical Society,Enantioselective Total Synthesis of (−)-Strychnine Using the Catalytic Asymmetric Michael Reaction and Tandem Cyclization,"The enantioselective total synthesis of (-)-strychnine was accomplished through the use of the highly practical catalytic asymmetric Michael reaction (0.1 mol % of (R)-ALB, more than kilogram scale, without chromatography, 91% yield and >99% ee) as well as a tandem cyclization that simultaneously constructed B- and D-rings (>77% yield). Moreover, newly developed reaction conditions for thionium ion cyclization, NaBH3CN reduction of the imine moiety in the presence of Lewis acid to prevent ring opening reaction, and chemoselective reduction of the thioether (desulfurization) in the presence of exocyclic olefin were pivotal to complete the synthesis. The described chemistry paves the way for the synthesis of more advanced Strychnos alkaloids.",10.1021/ja028457r,2002-11-13,0.6162637833808242
Synlett,Asymmetric Total Synthesis of ent-Tetrahydrolipstatin from an Epoxy Alkenol,A highly efficient asymmetric total synthesis of ent -­tetrahydrolipstatin (THL) was accomplished from the known epoxy alkenol. The β-lactone portion of THL was synthesized by the epoxide opening with cyanide and stereoselective enolate alkylation method. The side chain was introduced by cross metathesis of the alkene part with 1-decene. Coupling with a protected leucine completed the synthesis of ent -tetrahydrolipstatin.,10.1055/s-0031-1290407,2012-07-01,0.6162567851958158
Journal of Organic Chemistry,Formal Synthesis of Ecteinascidin 743 from <i>N</i>-Cbz-<scp>l</scp>-tyrosine,"A formal total synthesis of ecteinascidin 743 and lurbinectedin is achieved. Key features involve a Pictet–Spengler cyclization coupling of the tetrahydroisoquinoline and phenylalaninol moieties prepared by a common route with high yield and selectivity, a Parikh–Doering oxidation with good chemoselectivity and functionality tolerance, and a light-mediated A-ring elaboration of pentacyclic methoxyquinone substrates. By the approach, the known advanced intermediate (4-step conversion to Et-743) can be obtained conveniently in 21 total steps from N -Cbz- l -tyrosine.",10.1021/acs.joc.3c00931,2023-07-18,0.6162531686379055
Synlett,Total Synthesis of the Angucylinone Antibiotic (+)-Rubiginone B<sub>2</sub>,"A new chiral synthesis of (+)-rubiginone B2 is reported. The intramolecular cobalt-mediated [2+2+2]-cycloaddition of a triyne precursor, synthesized from (+)-citronellal, afforded a chiral anthracene, which led after a two-step oxidation to the angucycli­none antibiotic.",10.1055/s-2003-41473,2003-01-01,0.6162510266609434
Journal of Organic Chemistry,Intramolecular Dearomative Inverse-Electron-Demand Diels Alder Strategy for the Total Synthesis of (+)-Alstonlarsine A,"An evolution of a synthetic route leading to a successful enantioselective total synthesis of monoterpenoid indole alkaloid (+)-alstonlarsine A is represented. The unique 9-azatricyclo[4.3.1.0 3,8 ]decane core was assembled through an efficient domino sequence comprising enamine formation in situ, followed by intramolecular dearomative inverse-electron-demand Diels Alder reaction. The preparation of the tricyclic dihydrocyclohepta[ b ]indole key intermediate via the intramolecular Horner–Wadsworth–Emmons reaction required a development of a new general method for the introduction of the phosphonoacetate moiety into the indole C-2 position, through copper-carbenoid insertion. The modular nature of the represented synthetic approach makes it suitable for the synthesis of analogues with different substituents’ patterns.",10.1021/acs.joc.3c00923,2023-08-09,0.6162383618945941
Journal of Organic Chemistry,"Efficient Synthesis of the A-Ring Phosphine Oxide Building Block Useful for 1α,25-Dihydroxy Vitamin D<sub>3</sub>and Analogues","The 1 alpha-hydroxy A-ring phosphine oxide 1, a useful building block for vitamin D analogues, was synthesized from (S)-carvone in nine synthetic operations and a single chromatographic purification in 25% overall yield. The synthesis features two novel efficient synthetic transformations: the Criegee rearrangement of alpha-methoxy hydroperoxyacetate 10 in methanol to obtain directly the desired secondary 3 beta-alcohol 11 and the highly chemo- and stereoselective isomerization of dieneoxide ester (E)-7 to the 1 alpha-allylic alcohol with an exocyclic double bond (E)-8. Further insight into the selectivity control of the latter rearrangement was obtained from the reactions of (Z)-epimeric substrates. The new synthetic approach leading to the 1 alpha-hydroxy epimers complements our previously reported synthesis of the corresponding 1 beta-epimers, thus producing all stereoisomers of these versatile building blocks efficiently from carvone.",10.1021/jo0161577,2002-02-09,0.616220187566154
Organic Process Research & Development,Process Development and Scale-Up of a Protease Inhibitor for the Treatment of HIV Featuring the Preparation of a Neopentyl Grignard Reagent and Development of a One-Pot Curtius Reaction,"Compound 1 is a densely functionalized iminohydantoin that possesses a quaternary stereocenter and is under development as an HIV protease inhibitor. Key challenges that are discussed include the preparation of a neopentyl Grignard reagent via magnesium insertion, development of a one-pot Curtius reaction that generated a volatile isocyanate and was trapped with an alcohol, and removal of a CBz protecting group to isolate a succinate salt. This study describes process development efforts that enabled the first scale-up of 1 .",10.1021/acs.oprd.2c00153,2022-08-18,0.6162110778457446
Tetrahedron,Fe(OTf) 3 -catalyzed practical synthesis of 2-trifluoromethylarylimidazoles from o -arylenediamines and hexafluoroacetylacetone,,10.1016/j.tetlet.2016.06.086,2016-06-27,0.6162110721210365
Journal of Organic Chemistry,Total Synthesis of the Serine/Threonine-Specific Protein Phosphatase Inhibitor Tautomycin<sup>1</sup>,"A convergent, asymmetric synthesis of the protein phosphatase inhibitor, tautomycin, is described. The natural product was constructed by joining two major fragments of comparable complexity at the C21-C22 bond. Absolute stereochemistry of the C1-C21 ketone originates from (S)-citronellene and (2R,3S)-geraniol epoxide. The anti stereochemical relationships at C6-C7 and C18-C19 were introduced with Duthaler's chiral titanium propionic enolate. Syn stereochemical relationships at C13-C14 and C23-C24 were established using an Evan's oxazolidinone chiral auxiliary. The spiroketal was efficiently constructed via a one-pot double-alkylation-spirocyclization sequence with acetone N,N-dimethylhydrazone serving as the central linchpin. Final coupling of the two halves using a chelation-controlled Mukaiyama aldol addition followed by deprotection yielded synthetic tautomycin that is identical to the natural product.",10.1021/jo961633s,1997-01-01,0.6162089244529549
Synlett,A New Route to 5-Aryl and 5-Heteroaryl-2-pyrones via Suzuki Coupling of a 2-Pyrone-5-boronate ester,The synthesis of the 2-pyrone-5-boronate ester 5 is described along with its palladium-catalysed coupling reactions with a range of aryl and heteroaryl halides and triflates.,10.1055/s-2003-36789,2003-01-01,0.6162044968150697
Angewandte Chemie International Edition,Enantioselective Total Synthesis of (−)‐Martinellic Acid,"An enantioselective total synthesis of martinellic acid is described. The pyrroloquinoline alkaloid core is efficiently prepared from a quinoline, employing a method which relies on a newly developed Cu-catalyzed enantioselective alkynylation using the chiral imidazole-based biaryl P,N ligand StackPhos to establish the absolute stereochemistry. The remaining carbon atoms are then installed by means of a diastereoselective Pd-catalyzed decarboxylative allylation and the synthesis is completed after straightforward functional-group manipulation. This new synthetic method enables the most concise enantioselective synthesis of this important class of molecules to date.",10.1002/anie.201507849,2015-11-17,0.6162009111063775
Organic Letters,"Isolation, Structure, and Total Synthesis of the Marine Macrolide Mangrolide D","The isolation, characterization, and total synthesis of the macrocyclic polyene mangrolide D is reported. A 16-step total synthesis relies on robust Suzuki and ring-closing metathesis reactions, and an iron-catalyzed hydroazidation of an exomethylene substituted tetrahydropyran as a key step for the synthesis of the appended 4- epi-vancosamine sugar. Although mangrolide D did not display antibiotic activity, this work should prove enabling toward the synthesis of the antitubercular tiacumicins which display a virtually identical macrocyclic backbone.",10.1021/acs.orglett.9b01126,2019-04-08,0.6161990567070763
Angewandte Chemie International Edition,Synthesis of (−)‐(<i>Z</i>)‐Deoxypukalide,"Closing the deal: A ring-closing metathesis (RCM)/aromatization protocol, followed by a regioselective Negishi cross-coupling reaction and macrolactonization, with subsequent RCM mediate the synthesis of (−)-(Z)-deoxypukalide in 12 linear steps and 15 % overall yield (see retrosynthesis; TBS=tert-butyldimethylsilyl, TIPS=triisopropylsilyl).",10.1002/anie.200802703,2008-08-08,0.6161948038431968
Journal of the American Chemical Society,Total Synthesis of the Anti Methicillin-Resistant<i>Staphylococcus aureus</i>Peptide Antibiotics TAN-1057A-D,"TAN-1057A−D, dipeptides isolated from bacteria Flexibacter sp. PK-74 and PK-176, are new antibiotics with potent antibacterial activity against methicillin-resistant Staphylococcus aureus . We describe, in detail, the total synthesis of TAN-1057A−D by a convergent route featuring a new method to construct the cyclic amidinourea functional group.",10.1021/ja972670j,1997-12-01,0.6161928086167504
Organic Process Research & Development,Development of an Efficient Manufacturing Process for E2212 toward Rapid Clinical Introduction,"Process studies of E2212 ( 1 ) toward rapid clinical introduction are described. Through comprehensive route-finding studies and optimization of key condensation and cyclization steps, a racemate-based manufacturing route was established and successfully scaled-up to the hundred kilogram scale. For the rapid delivery of a drug substance containing the Z isomer for preclinical safety studies, the successful scale-up of the photoisomerization of an olefin in a flow system is also presented.",10.1021/acs.oprd.8b00444,2019-03-27,0.6161752864146496
Synthesis,"An Improved Synthesis of Bicyclo[9.3.1]pentadeca-1(15),11,13-trien-15-oI (15-Hydroxy[9]metacyclophane)",All articles of this category A seven-step synthesis of the title compound in 40 % overall yield from cyclododecanone is described. The stereochemistries of some of the intermediates were determined from their NMR spectra.,10.1055/s-1991-26415,1991-01-01,0.6161711929259872
Journal of the American Chemical Society,Total Synthesis of (−)-Retigeranic Acid A: A Reductive Skeletal Rearrangement Strategy,"The asymmetric total synthesis of (-)-retigeranic acid A was described, which relies on a crucial reductive skeletal rearrangement cascade for the controllable assembly of diverse angular triquinane subunits. Taken together with an intramolecular Michael/aldol cyclization, an ODI-[5 + 2] cycloaddition/pinacol rearrangement cascade, a Wolff ring contraction and a stereoselective HAT reduction, our synthetic approach has enabled the access to (-)-retigeranic acid A in a concise and practical manner.",10.1021/jacs.3c03178,2023-05-24,0.6161540733200047
Tetrahedron,Palladium(0)-catalyzed reaction of propargylic phosphates with SmI2: A highly regioselective route to the synthesis of allenes and acetylenes,,10.1016/0040-4039(94)02357-h,1995-02-01,0.6161498294915456
Organic Letters,Asymmetric Synthesis of (−)-Adaline,"[reaction: see text] An enantioselective total synthesis of (-)-adaline has been achieved starting from a chiral 6,6-disubstituted piperidone derivative previously prepared by diastereoselective allylation of a chiral tricyclic N-acyl-N,O-acetal. The key steps include lithium ion-activated SN2-type alkynylation of the tricyclic N,O-acetal leading to exclusive formation of the (6S)-ethynylpiperidine and ring-closing olefin metathesis of the (2R,6S)-cis-2,6-dialkenylpiperidine for constructing the bridged azabicyclononane.",10.1021/ol0200807,2002-06-29,0.6161469930907453
Organic Letters,"Practical, Asymmetric Route to Sitagliptin and Derivatives: Development and Origin of Diastereoselectivity","The development of a practical and scalable process for the asymmetric synthesis of sitagliptin is reported. Density functional theory calculations reveal that two noncovalent interactions are responsible for the high diastereoselection. The first is an intramolecular hydrogen bond between the enamide NH and the boryl mesylate S═O, consistent with MsOH being crucial for high selectivity. The second is a novel C-H···F interaction between the aryl C5-fluoride and the methyl of the mesylate ligand.",10.1021/acs.orglett.5b00520,2015-03-23,0.6161315485966271
Tetrahedron,A general synthetic route to A-ring hydroxylated vitamin D analogs from pentoses,,10.1016/0040-4039(94)02209-t,1995-01-01,0.6161265094380888
Synlett,Synthesis of Ureidothiazolines,"All articles of this category A one-step synthesis of ureidothiazolines from 1-aryl- and 1,6-diaryl-2-thiobiureas by its reaction with α -haloketones is described. basicity - cyclization - condensation - nucleophilic - heterocycles",10.1055/s-2001-11399,2001-12-31,0.6161150172661759
Angewandte Chemie International Edition,A Biomimetic Synthesis of (±)‐Basiliolide B,"A highly diastereoselective and practical biomimetic total synthesis of (±)-basiliolide B has been achieved through the study of the two proposed biosynthetic pathways (O-methylation and O-acylation) for the unprecedented 7-methoxy-4,5-dihydro-3H-oxepin-2-one (C ring). The synthesis featured a cyclopropanation/ring opening strategy for establishing the stereogenic centers at C8 and C9, a biomimetic 2-pyrone Diels-Alder cycloaddition for the synthesis of the ABD ring system, and finally a highly efficient biomimetic intramolecular O-acylation for the C ring formation. This result provides an important perspective on the biosynthetic origin of the unprecedented 7-membered acyl ketene acetal moiety of the C ring.",10.1002/anie.201405770,2014-08-27,0.6161130060494691
Synthesis,"An Approach to the Synthesis of a Hepatitis C Virus Inhibitor through a Proline-Catalyzed 1,3-Dipolar Cycloaddition Using Acrolein","Abstract An efficient and easy protocol for performing 1,3-dipolar cycloaddition using azomethine ylides and acrolein is presented. The reaction catalyzed by d-proline allows the synthesis of C-3 unsubstituted pyrrolidines. The application of this methodology to the synthesis of an advanced intermediate in the preparation of a Hepatitis C virus inhibitor is presented. Final attempts to complete the synthesis of the target inhibitor results in the preparation of its C-4 epimer in good overall yield.",10.1055/s-0040-1719858,2021-12-06,0.6161112327801362
Angewandte Chemie International Edition,A Concise Enantioselective Total Synthesis of (−)‐Virosaine A,"The total synthesis of (-)-virosaine A (1) was achieved in ten steps starting from furan and 2-bromoacrolein. A one-pot Diels-Alder cycloaddition/organolithium addition initiated an efficient sequence to access a key oxime/epoxide intermediate. Heating this intermediate in acetic acid resulted in an intramolecular epoxide opening/nitrone [3+2] cycloaddition cascade to construct the caged core of 1 in a single step. Several methods of C-H functionalization were assessed on the cascade product, and ultimately, a directed lithiation/bromination effected selective C14 functionalization, enabling the synthesis of 1.",10.1002/anie.201706273,2017-07-11,0.6161042914949012
Synlett,"Synthesis of a Novel Octahydro Pyrrolo[3,4-c]pyrrole Cyclic Amidine via 1,3-Dipolar Cycloaddition of Azomethine Ylides","A concise synthesis of fused bicyclic pyrrolidines via 1,3-dipolar cycloaddition of azomethine ylides is reported. The exo cycloadduct isomer enables the synthesis of a novel cyclic amidine toward the preparation of a potential human histamine H4 receptor antagonist. The minor endo isomer led to the isolation of a new triazine ring through an intramolecular reductive cyclisation",10.1055/s-0030-1260768,2011-06-01,0.6160927136357783
Synthesis,Acyloxymethyl Carbonochloridates. New Intermediates in Prodrug Synthesis,All articles of this category The synthesis of a number of stable acyloxymethyl carbonochloridates 7 has been accomplished in four steps from chloromethyl carbonochloridate 3 . Each step has been optimized with propanoyloxymethyl carbonochloridate 7c as a model compound (64% overall yield). Diethyl ether-boron trifluoride catalyzes the conversion of carbonothioate 6cc to the carbonochloridate 7c by chlorination with sulfuryl chloride. Acylation of a few compounds containing hydroxy or amino groups by 7c is described.,10.1055/s-1990-27124,1990-01-01,0.6160875261049505
Synthesis,"Efficient Multigram Syntheses of Air-Stable, Fluorescent Primary Phosphines via Palladium-Catalyzed Phosphonylation of Aryl Bromides","Air-stable, fluorescent primary phosphines have been prepared on a multigram scale. The two key synthetic steps are an optimized palladium-catalyzed phosphonylation of aryl bromides and a boron–carbon bond formation reaction. The method provides a valuable synthetic route to novel fluorescent derivatives via a key phosphonate intermediate.",10.1055/s-0034-1378336,2014-07-24,0.6160784337501792
Synlett,A Convergent Synthesis of the C31-C46 Fragment of Phorboxazoles,"A convergent synthesis of the C31-C46 fragment of phorboxazoles has been achieved. This involved the preparation of a C31-C39 aldehyde and a C40-C46 benzothiazole secondary sulphone followed by their coupling, employing modified Julia olefination as a key reaction.",10.1055/s-2004-829543,2004-01-01,0.6160737002491247
Organic Letters,Total Synthesis of Chaetoquadrins A–C,"The first total synthesis of the monoamine oxidase inhibitors chaetoquadrins A-C has been accomplished. Key steps in the synthesis include an aromatic Claisen rearrangement, asymmetric boron aldol reaction and acid-mediated spiroketalization. Comparison of spectral data for the synthetic spiroketals confirmed the proposed structure for these natural products.",10.1021/ol303482k,2013-01-17,0.6160735104116466
Journal of Organic Chemistry,"Synthesis of (<i>R</i>)-Boc-2-methylproline via a Memory of Chirality Cyclization. Application to the Synthesis of Veliparib, a Poly(ADP-ribose) Polymerase Inhibitor","( R)-Boc-2-methylproline (3a) was synthesized in good yield with excellent stereochemical control from alanine benzyl ester hydrochloride 11. The process, which is based on a modification of one described by Kawabata, proceeds in four steps and requires no chromatography. The product ( R)-Boc-2-methylproline (3a) was then carried forward in three steps to produce veliparib 1, a poly(ADP-ribose) polymerase inhibitor.",10.1021/acs.joc.8b02866,2019-02-04,0.6160713222543438
Tetrahedron,Enantioselective route to α-hydroxy aldehyde and acid derivatives,,10.1016/s0040-4039(00)93537-8,1991-10-01,0.6160712004491169
Organic Process Research & Development,"Development of a Scalable Process for an IL-17A Inhibitor LY3509754: Part III. Assembly of Drug Substance, Salt Formation, and Impurity Control","A 5-step cGMP sequence for the preparation of an IL-17A inhibitor 1 was optimized and scaled up to deliver a total of 66 kg of the final drug substance 1 to support clinical and product development studies. Salt formation and polymorph screening identified a suitable polymorph of the hemiedisylate salt that provided desirable physical properties. Key impurities in the final drug substance were identified, and control strategies were developed and executed to control them to acceptable levels in the production batches.",10.1021/acs.oprd.5c00005,2025-04-02,0.6160680074235394
Tetrahedron,A practical enantioselective total synthesis of (−)-(S)-stepholidine,,10.1016/j.tetlet.2014.05.034,2014-05-21,0.6160662606700027
Organic Letters,"Highly Efficient Copper-Catalyzed Domino Ring Opening and Goldberg Coupling Cyclization for the Synthesis of 3,4-Dihydro-2<i>H</i>-1,4-benzoxazines","trans-3,4-Dihydro-2H-1,4-benzoxazine moieties can be synthesized by domino aziridine ring opening with o-iodophenols followed by the copper-catalyzed Goldberg coupling cyclization (intramolecular C(aryl)-N(amide) bond formation) with good to excellent yields.",10.1021/ol9003299,2009-04-02,0.6160654627510205
Synlett,A Short and Enantiospecific Synthesis of (-)-Nupharamine,A short and convergent synthesis of the naturally ­occurring sesquiterpenoid piperidine alkaloid (-)-nupharamine is presented starting from (-)-isopinocampheol via cross metathesis and reductive amination as the key steps.,10.1055/s-2005-918942,2005-01-01,0.6160431466014307
Journal of Organic Chemistry,Stereocontrolled Preparation of a Nonpeptidal (−)-Spirobicyclic NK-1 Receptor Antagonist,The synthesis of a spirobicyclic NK-1 receptor (Substance-P) antagonist 1 antipode is described. Retrosynthetic analysis reveals an allylic halide A bearing the cyclopropoxy-substituted aryl group and a 2-phenyl-3-piperidone B. The stereochemistry in the spirobicyclic system bearing three chiral centers is initially set via a highly diastereoselective zinc-mediated coupling of the allylic bromide 23 to the optically active ketopiperidine 3. The remaining benzylic asymmetric center is set by a diastereoselective hydroboration followed by cyclization to the spirobicyclic system.,10.1021/jo0157472,2002-01-22,0.6160209862383471
Organic Letters,"Tandem [5 + 2]/[4 + 2] Cycloadditions To Construct the [6–7–6] Tricyclic Skeleton of Icetexane Diterpenes: Total Synthesis of Euolutchuol E, Przewalskine E and Brussonol","The collective total synthesis of the icetexane diterpenoids euolutchuol E, przewalskine E, and brussonol is described. An efficient synthetic strategy features two key transformations: (a) a tandem [5 + 2]/[4 + 2] cycloaddition reaction strategy to efficiently build the full-carbon skeleton of the icetexane diterpenoids; (b) an efficient aromatization of the C-ring of the icetexane diterpenoids using SeO 2 .",10.1021/acs.orglett.0c02309,2020-09-18,0.6160095772226647
Tetrahedron,"A novel, two-step synthesis of 4-pyridone-3-carboxamides from 2-cyano-4-pyrones",,10.1016/j.tetlet.2013.03.132,2013-04-17,0.6160056725917418
Organic Process Research & Development,Pilot-Plant Preparation of an α<sub>v</sub>β<sub>3</sub> Integrin Antagonist. Part 3. Process Research and Development of a Diisopropylcarbodiimide and Catalytic 1-Hydroxybenzotriazole Peptide Coupling,"Studies directed toward the process research, development, and scale-up preparation of the potential α v β 3 integrin antagonist 1 are described. A convergent approach is detailed wherein tetrahydropyrimidine hydroxybenzoic acid 2 is linked to the β-amino acid ester 3 via a diisoproylcarbodiimide, catalytic HOBt coupling reaction. Saponification of the resulting ethyl ester, isolation of the corresponding zwitterion, H 3 PO 4 salt formation, crystallization, and acetonitrile-to-acetone exchange give rise to 1 as a crystalline monohydrate in 67% overall yield from 4 .",10.1021/op900173f,2009-09-04,0.6159967431109294
Journal of the American Chemical Society,Bioinspired Divergent Synthesis of Aspersteroids A and B,"Aspersteroids A and B are novel ergostane-type 18,22-cyclosterols with immunosuppressive and antimicrobial activities. Herein, we report the first synthesis of these two natural products, which was accomplished in 15 and 14 steps, respectively, from commercially available ergosterol by means of a bioinspired divergent approach. Key features of this synthesis include an unprecedented radical relay cyclization that was initiated by iron(II)-mediated decomposition of an alkyl hydroperoxide to construct the E ring cyclopentane motif; a titanium(III)-mediated diastereoselective radical reduction of an epoxide to install the challenging C22 stereocenter; and highly regioselective, divergent late-stage oxidations to access the highly oxidized core framework.",10.1021/jacs.4c01016,2024-02-29,0.6159867086731494
Tetrahedron,"A convenient synthetic route to substituted pyrrolo[2,3-b]pyridines via a novel ethylene-bridged compound",,10.1016/j.tetlet.2015.10.031,2015-10-17,0.6159839966950547
Tetrahedron,Application of chiral (E)-crotylsilanes in synthesis: The asymmetric synthesis of the C1C17 polypropionate fragment of rutamycin B,,10.1016/s0040-4039(97)00095-6,1997-02-01,0.6159825904776026
Tetrahedron,"Concise synthesis of 2-N-hydroxy-3,4-dihydroisoquinol-2-one: A bacterial siderophore and human 5-lipooxygenase inhibitor",,10.1016/j.tetlet.2018.03.017,2018-03-08,0.6159704178965331
Journal of Organic Chemistry,"Isoxazole Strategy for the Synthesis of 2,2′-Bipyridine Ligands: Symmetrical and Unsymmetrical 6,6′-Binicotinates, 2,2′-Bipyridine-5-carboxylates, and Their Metal Complexes","An effective strategy was developed for the synthesis of new 2,2′-bipyridine ligands, symmetrical and unsymmetrical 6,6′-binicotinates, and 2,2′-bipyridine-5-carboxylates, from 4-propargylisoxazoles. The synthesis of symmetrical 2,2′-disubstituted 6,6′-binicotinates was achieved using the Eglinton reaction of 5-methoxy-4-(prop-2-yn-1-yl)isoxazoles with Cu(OAc) 2, followed by Fe(NTf 2 ) 2 /Au(NTf 2 ) t BuXPhos-catalyzed isomerization of the so-formed mixture of isoxazole/azirine-substituted biacetylenic intermediates. Unsymmetrical 2,2′-disubstituted 6,6′-binicotinates were prepared via a copper-free Sonogashira coupling of 5-methoxy-4-(prop-2-yn-1-yl)isoxazoles with 6-bromonicotinates to give methyl 6-(3-(5-methoxyisoxazol-4-yl)prop-1-ynyl)pyridine-3-carboxylates, followed by a transformation of the propargylisoxazole moiety of the adduct into the pyridine fragment under Fe(II)/Au(I) relay catalysis conditions. 6-(Pyrid-2-yl)nicotinates were synthesized by a Stille-type coupling of 2-(tributylstannyl)pyridine with 6-bromonicotinates. Several cyclopalladated complexes of a new series of 6,6′-binicotinates and 2,2′-bipyridine-5-carboxylates and the homoleptic Cu(I) complex were synthesized in high yields.",10.1021/acs.joc.9b00115,2019-02-27,0.6159699660584042
Organic Letters,Synthesis of Pyranicin and Its Inhibitory Action with Bovine Heart Mitochondrial Complex I,Total synthesis of pyranicin was achieved using Cl2Pd(CH3CN)2-catalyzed diastereoselective cyclization of the allylic ester as the key step. The inhibitory activity of this compound for mitochondrial NADH-ubiquinone oxidoreductase (complex I) was slightly poorer than that of ordinary mono-THF acetogenins such as cis-solamin.,10.1021/ol702902w,2008-02-06,0.6159432178903447
Tetrahedron,Synthesis of glucuronic acid derivatives via the efficient and selective removal of a C6 methyl group,,10.1016/j.tetlet.2016.12.055,2016-12-23,0.6159394021277469
Synthesis,Asymmetric Synthesis of 4′-<i>epi</i>-Trachycladines A and B,"The first asymmetric synthesis of 4′-epi-trachycladines A and B is reported. Starting from 2,2-dimethyl-1,3-dioxan-5-one the title nucleosides were synthesised in 14 steps employing the SAMP-/RAMP-hydrazone methodology. The dioxanone-SAMP-hydrazone was first transformed into a trisubstituted derivative by a triple α-/α′-alkylation. Removal of the chiral auxiliary and subsequent reduction gave the corresponding alcohol, which could be transformed over four steps into TBS-protected 2′-C-methyl-5′-deoxy-l-lyxose. The trachycladines were then obtained via the corresponding triacetate using standard Vorbrüggen and silyl-Hilbert-Johnson conditions in an overall yield of 18-21%. Such 2′-C-branched ribonucleosides are potential agonists for adenosine receptors and play an important role in drug discovery.",10.1055/s-2005-918439,2005-01-01,0.6159370832736598
Journal of Organic Chemistry,Synthesis of Two Unnatural Oxygenated Aaptaminoids,"Two unprecedented oxygenated aaptaminoids have been synthesized starting from cheap and easily available 2,3-dihydroxybenzoic acid with the satisfactory overall yields of 31% and 34%. The key step of the procedure is the divergent thermic 5-exodig vs base-promoted 6-endodig cyclization of a 5-alkynylquinolinone derivative.",10.1021/jo3020598,2012-10-22,0.6159325011187559
Journal of the American Chemical Society,Total Synthesis of (+)-Mutilin: A Transannular [2+2] Cycloaddition/Fragmentation Approach,"A new and enantioselective total synthesis of the diterpenoid (+)-mutilin is described. Following a Claisen rearrangement approach to construct the 6,9-bicycle, a transannular [2+2] photocycloaddition and the ensuing ring-opening reaction were implemented to forge the characteristic 5-6-8 propellane-like skeleton. Subsequent late-stage alkylations and reduction completed the synthesis.",10.1021/jacs.2c06934,2022-08-22,0.6159241882653066
Journal of Organic Chemistry,"Unified Total Synthesis of Tetracyclic Diquinane <i>Lycopodium</i> Alkaloids (+)-Paniculatine, (−)-Magellanine, and (+)-Magellaninone","alkaloids (+)-paniculatine, (-)-magellanine, and (+)-magellaninone has been accomplished in 13-14 overall steps based on late-stage diverse transformations from an advanced tetracyclic common intermediate. In the established synthesis, quick formation of the two five-membered rings was efficiently achieved by an intramolecular reductive coupling of ketone-carbonyl and ester-carbonyl and an organocatalytic intramolecular Michael addition of aldehyde-derived enamine to an internal enone functionality with satisfactory redox and step economies and excellent stereoselectivities, providing the requisite tricyclic carbo-framework possessing multiple dense stereogenic centers, and an intramolecular reductive amination finally furnished the essential piperidine ring.",10.1021/acs.joc.2c00871,2022-06-14,0.6159233819881567
Tetrahedron,An efficient synthesis of 4-benzoyloxyazetidinone: an important carbapenem intermediate,,10.1016/0040-4039(88)85207-9,1988-01-01,0.6159218255546549
Tetrahedron,"Method for synthesis of 12H-pyrido[1,2-a:3,4-b']diindoles. Total synthesis of homofascaplysin C",,10.1016/0040-4039(96)01052-0,1996-07-01,0.6159066271386533
Organic Letters,Total Synthesis of (±)-Cylindricine C,"A concise synthesis of (±)-cylindricine C and its C(13)-epimer is described. Starting from 1-octyne, cylindricine C and 13-epi-cylindricine C were prepared in 11% and 15% yields, respectively. The synthesis involves the preparation of the central tricyclic moiety via a radical α-iodoketone carboazidation/bis-reductive amination sequence. Inversion of the stereochemistry at C(13) and C(5) was efficiently achieved on late stage intermediates.",10.1021/ol201745s,2011-08-12,0.6159002034567902
Organic Process Research & Development,A Concise Two-Step Synthesis of Thalidomide,A two-step synthesis of thalidomide is presented. The sequence requires no purifications. Treatment of l -glutamine with N -carbethoxyphthalimide produces N -phthaloyl- l -glutamine. Cyclization of N -phthaloyl- l -glutamine to afford thalidomide is accomplished by treatment with CDI in the presence of a catalytic amount of DMAP.,10.1021/op980201b,1999-03-01,0.6158968745619205
Tetrahedron,Highly efficient total synthesis of manoalide and seco-manoalide via Pd(0) catalyzed coupling of allyhalide with CO and 2-silyl-4-stannylfuran,,10.1016/s0040-4039(00)86680-0,1988-01-01,0.615892241407721
Tetrahedron,Synthesis of fused tricyclic β-lactams by the Pauson-Khand cyclization of enyne-2-azetidinones,,10.1016/0040-4039(96)01511-0,1996-09-01,0.6158836335429699
Tetrahedron,Synthesis of pinguisanes through furan-terminated cationic cyclization,,10.1016/s0040-4039(00)97617-2,1990-01-01,0.6158836335429699
Tetrahedron,From penicillin to penem and carbapenem. V Synthesis ofcarbapenam skeleton by (3 + 2) cyclization,,10.1016/s0040-4039(01)91547-3,1984-01-01,0.6158836335429699
Tetrahedron,Synthesis of 3-methoxyquinolines via cyclization of 1-isocyano-2-(2-lithio-2-methoxyethenyl)benzenes,,10.1016/s0040-4039(03)01040-2,2003-05-27,0.6158836335429699
Tetrahedron,Synthesis of pyrethroids via epxoyamide cyclization,,10.1016/s0040-4039(00)87099-9,1982-01-01,0.6158836335429699
Tetrahedron,π-Cyclization: The synthesis of (±)-solavetivone and (±)-hinesol,,10.1016/s0040-4039(01)82858-6,1981-01-01,0.6158836335429699
Tetrahedron,The synthesis of β-lactams by the cyclization of β-halopropionamides,,10.1016/s0040-4039(01)85997-9,1979-01-01,0.6158836335429699
Tetrahedron,Synthesis of benzo fused dioxadiazasilamacrocycles via remote dianion cyclization,,10.1016/j.tetlet.2012.09.106,2012-10-22,0.6158836335429699
Tetrahedron,Synthesis of 7-azabicyclo[2.2.1]heptanes by anionic cyclization,,10.1016/s0040-4039(99)00018-0,1999-02-01,0.6158836335429699
Tetrahedron,Synthesis of (+)-dihydrocompactin and (+)-compactin via vinylsilane terminated cationic cyclization,,10.1016/s0040-4039(00)92272-x,1991-01-01,0.6158836335429699
Tetrahedron,Synthesis of (+)-fragolide and (−)-pereniporin B via vinylsilane terminated cationic cyclization,,10.1016/s0040-4039(00)92273-1,1991-01-01,0.6158836335429699
Journal of the American Chemical Society,Total Synthesis of Dysidiolide,"The cdc25A protein phosphatase inhibitor dysidiolide ( 1 ) has been synthesized enantioselectively, starting from the enantiomerically pure ketal enone 2 and using a cationic rearrangement as the key step to produce the fully substituted bicyclic core of the natural product. Once the central portion of 1 was established, elaboration of the side chains was accomplished expediently via steps that included (1) vinyl cuprate displacement of an iodide to complete the C-1 side chain, (2) a highly diastereoselective oxazaborolidine-catalyzed (CBS) reduction to form carbinol 11, and (3) photochemical oxidation of 11 to generate the γ-hydroxybutenolide functionality of 1 . Additionally, this synthesis proves the absolute stereochemistry of dysidiolide ( 1 ).",10.1021/ja973023v,1997-12-01,0.615863240320071
Organic Letters,Divergent Synthesis of Eudesmane Sesquiterpenoids,"Demonstrated herein is a streamlined, unified strategy for the asymmetric, protecting-group-free synthesis of seven oxidized eudesmane congeners. A hydroxy-functionalized decalin scaffold bearing two orthogonally reactive olefins is constructed via an enantioselective tandem Michael addition–Aldol sequence, followed by a stereoselective Au(I)-catalyzed Alder-ene cyclization to establish the eudesmane core. Subsequent strategic late-stage hydrogenation and epoxidation enabled short and scalable access to structurally diverse eudesmane congeners, underscoring the platform’s broad potential for complex terpenoid synthesis.",10.1021/acs.orglett.5c03541,2025-10-06,0.6158577333068036
Organic Process Research & Development,Two Scalable Syntheses of 3-(Trifluoromethyl)cyclobutane-1-carboxylic Acid,"Two efficient synthetic methods for preparation of 3-(trifluoromethyl)cyclobutane-1-carboxylic acid are reported starting from readily available 4-oxocyclobutane precursors. These cyclobutanones can be converted to their CF 3 carbinols upon treatment with TMSCF 3 and a fluoride source. The bis-carboxylate system 9 was deoxygenated by treatment of Bu 3 SnH and provided desired compound 1 upon decarboxylation. In the monocarboxylate system 15, the triflate could be efficiently eliminated; subsequent hydrogenation afforded cis - 1 .",10.1021/acs.oprd.0c00422,2020-12-21,0.6158575024675456
Organic Letters,A Tandem Cross-Coupling/S<sub>N</sub>Ar Approach to Functionalized Carbazoles,"A novel route to functionalized carbazoles utilizing a tandem Suzuki cross-coupling/SNAr protocol is described. This process was found to be compatible with a variety of electron-withdrawing groups including aldehydes, esters, and sulfones. Using this method, a concise total synthesis (four steps, 50% overall yield) of the carbazole alkaloid glycosinine was achieved.",10.1021/ol702274y,2007-10-16,0.615850419239477
Organic Letters,A Ring-Closing Metathesis-Based Approach to the Synthesis of (+)-Tetrabenazine,"A modular stereoselective synthesis of the vesicular monoamine transport inhibitors (+)-tetrabenazine ((+)-1) and (+)-α-dihydrotetrabenazine ((+)-2) has been developed. The approach is based on amine 4 and acid 5 as the key building blocks, which were elaborated into macrolactam 3 by amide coupling and a subsequent highly E-selective RCM reaction. Macrolactam 3 could be converted into tetrabenazine in three known steps.",10.1021/ol301612q,2012-06-28,0.6158389883132497
Chemical Science,Concise total synthesis of (+)-gliocladins B and C,"The first total synthesis of (+)-gliocladin B is described. Our concise and enantioselective synthesis takes advantage of a new regioselective Friedel-Crafts-based strategy to provide an efficient multigram-scale access to the C3-(3'-indolyl)hexahydropyrroloindole substructure, a molecular foundation present in a significant subset of epipolythiodiketopiperazine natural alkaloids. Our first-generation solution to (+)-gliocladin B involved the stereoselective formation of (+)-12-deoxybionectin A, a plausible biosynthetic precursor. Our synthesis clarified the C15 stereochemistry of (+)-gliocladin B and allowed its full structure confirmation. Further studies of a versatile dihydroxylated diketopiperazine provided a concise and efficient synthesis of (+)-gliocladin B as well as access to (+)-gliocladin C.",10.1039/c2sc20270k,2012-01-01,0.615832125479798
Angewandte Chemie International Edition,A Short and Efficient Synthesis of Neodysiherbaine A by Using Catalytic Oxidative Cyclization,To the point: The synthesis of the title compound was achieved with 24 % overall yield through a sequence that has just seven linear steps (see scheme). Key points are the facial selectivity displayed by an oxocarbenium ion derived from a ribopyranose system and an osmium-catalyzed oxidative cyclization that is compatible with several acid-sensitive groups.,10.1002/anie.201102525,2011-06-27,0.6158245935532627
Organic Letters,Synthesis of Tetramic Acid Derivatives via a Tandem Umpolung Alkylation/Reduction/Cyclization Reaction of γ-Hydrazono β-Ketoester,"An efficient method for the one-pot synthesis of tetramic acid derivatives was developed utilizing tandem umpolung N-alkylation/reduction/cyclization of γ-hydrazono β-ketoester. By using this reaction as a key step, the total synthesis of the 3-spiro 7-hydroxamic acid tetralin which possesses an HDAC inhibitory activity was also achieved.",10.1021/acs.orglett.0c00824,2020-03-31,0.6158201594929175
Synlett,"The Synthesis of AraBOX, aNew 4,4′-Bis(oxazoline), from Novel Pentitol-DerivedBis-β-amino Alcohols","The preparation of a novel phenyl 4,4′-bis(oxazoline) [AraBOX] is described. The novel ligand is prepared in two efficient steps from a bis-[(O-silyl)β-amino alcohol], via conversion into an intermediate bis(benzamide) followed by a one-pot deprotection-activation-ring closure (DARC) oxazoline formation. To our knowledge, this is the first reported synthesis of an oxazoline ring via this DARC method. The synthesis of two precursor bis-β-amino alcohols, (2R,4R)- and meso-2,4-diaminopentane-1,5-diol, derived from d-(+)-arabitol and xylitol, respectively, is also described.",10.1055/s-0029-1216731,2009-04-17,0.6158139488826525
Journal of Organic Chemistry,"Facile One-Step Synthesis of β-Alkoxy Lactone via Sequential Lactonization and 1,4-Addition of Alkoxide Group:  Total Synthesis of All Stereoisomers of Dihydrokawain-5-ol","We describe here a divergent total synthesis of all of the four stereoisomers of dihydrokawain-5-ol starting from alpha-D-glucose. The approach involves the use of Ando's modification of Horner-Wadsworth-Emmons homologation to give a alpha,beta-unsaturated ester. Subsequently, lactonization and 1,4-addition of OMe group in one step provided a delta-lactone, which was converted into the target compounds in two steps.",10.1021/jo049858n,2004-04-20,0.6158123193706019
Synthesis,A Concise Synthesis of Natural Benzofuran Neolignans and Analogues,"The first total synthesis of four naturally occurring benzofuran neolignans and two analogues was achieved in four steps in 44-51% overall yield. Key steps involved a two-step construction of benzofuran nucleus and a Suzuki coupling. This synthesis has been proven straightforward and efficient, and more related analogues can be prepared for structure-activity relationship explorations.",10.1055/s-0029-1218826,2010-06-17,0.6157983555848172
Tetrahedron,Total synthesis of the methyl glycoside of bradyrhizose via intramolecular pinacol coupling,,10.1016/j.tetlet.2022.154060,2022-08-04,0.6157966381729703
Organic Letters,Total Synthesis of 2-Isocyanoallopupukeanane: Construction of Caged Skeleton by Intramolecular Alkylation of Bromonitriles,"A new method for constructing the bicyclo[3.2.1]octane skeleton was developed by the intramolecular alkylation of a nitrile-side-chain-containing cyclohexanone derivative. The cyclization precursors were prepared via the stereoselective bromination of the triisopropylsilyl enol ethers of 4-substituted cyclohexanones. Upon treatment with LiNEt 2, the bromonitriles underwent a stereoselective intramolecular S N 2 reaction to afford bicyclo[3.2.1]octane derivatives with a cyano group on the convex face. The total synthesis of 2-isocyanoallopupukeanane (6.5% yield) from methyl vinyl ketone was accomplished via a 17-step transformation.",10.1021/acs.orglett.2c02434,2022-08-26,0.6157758941052743
Synthesis,N-tert-Butanesulfinyl Imines in Alkaloid Synthesis: Stereoselective Synthesis of (R)-Coniine and Formal Synthesis of (S)-δ-Coniceine¹,A stereoselective synthesis of the hemlock alkaloid (R)-coniine and a formal synthesis of the indolizidine alkaloid (S)-δ-coniceine were achieved by means of a highly diastereoselective Barbier-type indium-mediated allylation strategy involving (S)-(N-tert-butanesulfinyl)imines.,10.1055/s-0030-1260117,2011-07-14,0.6157706677524857
Organic Letters,Asymmetric Synthesis of a Fully Protected <i>e</i><i>nt</i>-Actinoidinic Acid,"[structure: see text] The asymmetric synthesis of a fully protected ent-actinoidinic acid derivative 14 is described. As key steps, an enantioselective deprotonation of an arene tricarbonylchromium(0) complex and a diastereoselective Suzuki coupling were applied. The asymmetric centers of the amino acid function were created via stereocontrolled Strecker reactions.",10.1021/ol016218n,2001-09-11,0.615763552176963
Synthesis,A New Efficient Synthesis of Iodomethyl Methyl Ether,,10.1055/s-1978-24820,1978-01-01,0.61575986267478
Journal of Organic Chemistry,"Enantioselective Synthesis of β-<scp>l</scp>-5-[(<i>E</i>)-2-Bromovinyl)-1-((2<i>S</i>,4<i>S</i>)-2-(hydroxymethyl)-1,3-(dioxolane-4-yl) Uracil)] (<scp>l</scp>-BHDU) <i>via</i> Chiral Pure <scp>l</scp>-Dioxolane","High Resolution Image Download MS PowerPoint Slide β- l -5-(( E )-2-Bromovinyl)-1-((2 S,4 S )-2-(hydroxymethyl)-1,3-(dioxolane-4-yl) uracil ( l -BHDU, 17 ) is a potent and selective inhibitor of the varicella-zoster virus (VZV). l -BHDU ( 17 ) has demonstrated excellent anti -VZV activity and is a preclinical candidate to treat chickenpox, shingles (herpes zoster), and herpes simplex virus 1 (HSV-1) infections. Its monophosphate prodrug (POM- l -BHDU-MP, 24 ) demonstrated an enhanced pharmacokinetic and antiviral profile. POM- l -BHDU-MP ( 24 ), in vivo, effectively reduced the VZV viral load and was effective for the topical treatment of VZV and HSV-1 infections. Therefore, a viable synthetic procedure for developing POM- l -BHDU-MP ( 24 ) is needed. In this article, an efficient approach for the synthesis of l -BHDU ( 17 ) from a readily available starting material is described in 7 steps. An efficient and practical methodology for both chiral pure l - & d -dioxolane 11 and 13 were developed via diastereomeric chiral amine salt formation. Neutralization of the amine carboxylate salt of l -dioxolane 10 provides enantiomerically pure l -dioxane 11 (ee ≥ 99%). Optically pure 11 was utilized to construct the final nucleoside l -BHDU ( 17 ) and its monophosphate ester prodrug (POM- l -BHDU-MP, 24 ). Notably, the reported process eliminates expensive chiral chromatography for the synthesis of chiral pure l - & d -dioxolane, which offers avenues for the development and structure–activity relationship studies of l - & d -dioxolane-derived nucleosides.",10.1021/acs.joc.4c00399,2024-06-20,0.6157591104644029
Journal of Organic Chemistry,"A Short, Enantioselective Synthesis of the AB-Ring Substructure of the Brevetoxins via <i>endo</i> -Selective Alkynol Cycloisomerization",,10.1021/jo970597+,1997-09-01,0.6157590882439798
Synlett,Asymmetric Synthesis of Mercaptoalcohols - Matrix Metalloproteinase Inhibitors,"All articles of this category A novel approach has been developed for the preparation of all of the possible diastereoisomers of mercaptoalcohol 1 , a potent matrix metalloproteinase (MMP) inhibitor, with easy access to various P1′ substituents. Readily available chiral epoxides have been used as the starting materials to control the stereochemistry of the -OH group. Mercaptoalcohol - MMP inhibitor - malonate alkylation - epoxide opening - decarboxylation",10.1055/s-1999-2858,1999-09-01,0.6157291156166602
Tetrahedron,An alternative synthesis for iloprost via a key bicyclic aldehyde intermediate,,10.1016/j.tetlet.2020.152627,2020-11-05,0.6157272673784774
Organic Letters,Organocatalytic Enantioselective Michael–Acetalization–Reduction–Nef Reaction for a One-Pot Entry to the Functionalized Aflatoxin System. Total Synthesis of (−)- Dihydroaflatoxin D<sub>2</sub> and (−)- and (+)-Microminutinin,"An efficient method has been developed for the enantioselective synthesis of the aflatoxin system with multiple stereocenters via a sequence of organocatalytic Michael–acetalization–reduction–Nef reactions that proceed with high enantioselectivities (90–99% ee). The one-pot reaction sequence provides a facile entry to the aflatoxin system, including dihydroaflatoxin D 2, which includes a formal total synthesis of aflatoxin B 2 . The first total synthesis of (−)- and (+)-microminutinin was also achieved via this protocol.",10.1021/acs.orglett.7b01473,2017-06-13,0.6157209258596232
Tetrahedron,A mild and efficient one-step synthesis of quinolines,,10.1016/j.tetlet.2005.01.075,2005-02-01,0.6157065795241476
Journal of Organic Chemistry,"Synthesis of a Sialic Acid Dimer Derivative, 2‘α-<i>O</i>-Benzyl Neu5Ac-α-(2→5)Neu5Gc","The preparation of a disaccharide 2, Neu5Ac-alpha-(2-->5)Neu5Gc having a alpha-benzyl protecting group at the reducing end, by the coupling of the easily accessible building units 4 and 5 is described. Subsequent deprotection of the coupling adduct led to the isolation of the target compound 2 in high yield.",10.1021/jo015930v,2002-01-22,0.615685710832284
Angewandte Chemie International Edition,Total Synthesis of the Cyclic Depsipeptide Vioprolide D via its (<i>Z</i>)‐Diastereoisomer,"The first total synthesis of vioprolide D was accomplished in an overall yield of 2.0 % starting from methyl (2S)-3-benzyloxy-2-hydroxypropanoate (16 steps in the longest linear sequence). The cyclic depsipeptide was assembled from two building blocks of similar size and complexity in a modular, highly convergent approach. Peptide bond formation at the C-terminal dehydrobutyrine amino acid of the northern fragment was possible via its (Z)-diastereoisomer. After macrolactamization and formation of the thiazoline ring, the (Z)-double bond of the dehydrobutyrine unit was isomerized to the (E)-double bond of the natural product. The cytotoxicity of vioprolide D is significantly higher than that of its (Z)-diastereoisomer.",10.1002/anie.202002328,2020-03-03,0.6156855107429643
Organic Letters,Phorboxazole Synthetic Studies. 1. Construction of a C(3−19) Subtarget Exploiting an Extension of the Petasis−Ferrier Rearrangement,"[formula: see text] In this, the first of two letters, we outline our overall strategy for the total synthesis of phorboxazoles A (1) and B (2), rare oxazole-containing macrolides possessing extraordinary antimitotic activity, and describe the assembly of a C(3-19) subtarget (-)-5 for the total synthesis of phorboxazole A. The synthesis of (-)-5 was achieved in 15 linear steps (12% overall yield), exploiting a modification of the Petasis-Ferrier rearrangement to construct the C(11-15) cis-tetrahydropyran. Dimethylaluminum chloride (Me2AlCl) proved to be the Lewis acid of choice for the Petasis-Ferrier rearrangement.",10.1021/ol990830l,1999-08-31,0.6156722693370348
Tetrahedron,Total synthesis of N-phthaloyl adda methyl ester: All stereocenters originating from a single chiral epoxyalcohol,,10.1016/s0040-4039(00)88911-x,1990-01-01,0.6156700931446085
Organic Letters,Short Route to Platencin,"The synthesis of the complex tricyclic core of the terpenoid antibiotic platencin is achieved in a concise, protecting group-free and stereoselective manner. A flexible approach that highlights the intramolecular aldol reaction as the key step toward the construction of the bicyclo[2,2,2]octane ring from an angular allyl decalone in both the trans-fused and the cis-fused forms is demonstrated.",10.1021/ol401760e,2013-07-08,0.615663569764662
Organic Letters,A Convergent Approach to the Mitomycin Ring System,"[structure: see text]. A novel stereoselective approach to the ring system of the mitomycins is described. The synthesis was based on a convergent strategy involving a stereocontrolled addition of a beta-phenyl silyl enol ether to a pyrroline N-acyliminium ion followed by an intramolecular palladium-catalyzed aryl triflate amination to afford the (9R*,9aR*)-tetrahydropyrrolo[1,2-a]indole ring system.",10.1021/ol0156244,2001-03-27,0.6156601359853381
Synthesis,A Facile Synthesis of 6-C-Prenylflavanones,"All articles of this category The first total synthesis of two natural 6- C -prenylflavanones, (±)-6- C -prenyleriodoctyol (1) and 6- C -prenylnaringenin (2) , using the acetophenone derivative 6 as the key intermediate is described. This new efficient synthetic approach was mainly based on Claisen rearrangement and cyclization reaction. 6- C -prenylflavanones - Claisen rearrangement - cyclization 2,4-bis(methoxymethoxy)-6-hydroxy-3-prenylacetophenone",10.1055/s-1997-1348,1997-11-01,0.6156473126310363
Tetrahedron,"Michael addition of ethyl acetoacetate to α,β-unsaturated oximes in the presence of FeCl3: a novel synthetic route to substituted nicotinic acid derivatives",,10.1016/s0040-4039(00)01391-5,2000-10-01,0.6156456367582698
Tetrahedron,"A new preparative route to chiral 2,3-epoxy-1,4-butanediols",,10.1016/s0040-4039(00)93588-3,1991-11-01,0.6156175027597051
Tetrahedron,The betaine-ylid route to trans-alkenols,,10.1016/s0040-4039(01)80805-4,1985-01-01,0.615615852517612
Tetrahedron,The spirooxirane route to trans-fused γ-lactones,,10.1016/0040-4039(81)80075-5,1981-01-01,0.615615852517612
Organic Process Research & Development,Optimized Synthesis of an Abemaciclib Intermediate: Improved Conditions for a Miyaura Borylation/Suzuki Coupling Process,"Improved reaction conditions have been developed for a telescoped Miyaura borylation/Suzuki coupling process, which is utilized in the synthesis of an abemaciclib intermediate. Key improvements include the in situ generation of a lipophilic base and tailored ligand selection for each palladium-catalyzed step. Optimizing ligand choice significantly reduced aryl scrambling, a major source of impurities in the borylation step. Additionally, the process improvements led to shortened reaction times and lower palladium loadings, resulting in a more efficient, higher-yielding process.",10.1021/acs.oprd.4c00381,2024-11-07,0.6156153813934201
Organic Letters,Asymmetric Transfer Hydrogenation of <i>rac</i>-α-(Purin-9-yl)cyclopentones via Dynamic Kinetic Resolution for the Construction of Carbocyclic Nucleosides,"An asymmetric transfer hydrogenation via dynamic kinetic resolution of a broad range of rac- α-(purin-9-yl)cyclopentones was first developed. A series of cis-β-(purin-9-yl)cyclopentanols were obtained with up to 97% yield, >20/1 dr, and >99% ee. This also provides an efficient synthetic route to a variety of chiral carbocyclic nucleosides.",10.1021/acs.orglett.9b00451,2019-04-02,0.6156048265486285
Angewandte Chemie International Edition,Total Synthesis of Palau’amine,"Worth the wait: The long anticipated total synthesis of palau'amine has been accomplished by a route featuring highly chemoselective transformations, cascade reactions, and a remarkable transannular cyclization to secure the unprecedented trans-5,5 ring junction (shown in red).",10.1002/anie.200907112,2009-12-29,0.615602107592523
Tetrahedron,Synthesis of a conformationally constrained threonine–valine dipeptide mimetic: design of a potential inhibitor of plasminogen activator inhibitor-1,,10.1016/s0040-4039(01)02080-9,2002-01-01,0.6155997878680741
Journal of Organic Chemistry,Convergent Synthesis of Sialyl Lewis<sup>X</sup>-<i>O</i>-Core-1 Threonine,"Selectins are a class of cell adhesion molecules that play a critical role during the initial steps of inflammation. The N-terminal domain of P-selectin glycoprotein ligand-1 (PSGL-1) binds to all selectins, but with the highest affinity to P-selectin. Recent evidence suggests that the blockade of P-selectin/PSGL-1 interactions provides a viable therapeutic option for the treatment of many inflammatory diseases. Herein, we report the total synthesis of threonine bearing sialyl Lewis X (sLe X ) linked to a Core-1- O -hexasaccharide 1, as a key glycan of the N-terminal domain of PSGL-1. A convergent synthesis using α-selective sialylation and a regioselective [4+2] glycosylation are the key features of this synthesis.",10.1021/acs.joc.7b03117,2018-04-11,0.6155891999832199
Tetrahedron,"A new, enantioselective synthesis of (+)-isolaurepan",,10.1016/j.tetlet.2009.07.041,2009-07-12,0.6155822757439434
European Journal of Organic Chemistry,"Synthesis of A‐Ring Precursors of 1α,25‐Dihydroxyvitamin D<sub>3</sub> Analogues Functionalized at C‐2","A flexible approach to an A‐ring building block for new 1α,25‐dihydroxyvitamin D analogues functionalized at C‐2 as potential clinical candidates is described. The synthesis of alcohol 5 starts from ( R )‐carvone, and uses a Criegee rearrangement to selectively degrade the isopropenyl side‐chain as one of the key steps.",10.1002/ejoc.201701258,2017-12-06,0.6155807512578401
Journal of Organic Chemistry,Synthesis of Vaniprevir (MK-7009): Lactamization To Prepare a 22-Membered Macrocycle,"Development of a practical synthesis of MK-7009, a 20-membered [corrected] macrocycle, is described. A variety of ring-closing strategies were evaluated, including ring-closing metathesis, intermolecular palladium-catalyzed cross-couplings, and macrolactamization. Ring closure via macrolactamization was found to give the highest yields under relatively high reaction concentrations. Optimization of the ring formation step and the synthesis of key intermediates en route to MK-7009 are reported.",10.1021/jo2011494,2011-08-12,0.6155770678942254
Organic Process Research & Development,Development of a Practical and Scalable Manufacturing Process for Ciprofol,"Ciprofol is a novel clinical anesthetic and is deemed a better alternative to propofol due to its fewer side effects. Herein, we report an atom-economical and cost-efficient manufacturing process to prepare Ciprofol, which includes regioselective para -halogenation of phenol, followed by esterification and Fries rearrangement in high yields. This strategy adopts para -halogenation to avoid the generation of para -byproducts in the Fries rearrangement. After a benign reduction of bromine and the Wittig reaction, the desired Ciprofol is achieved by ruthenium-catalyzed asymmetric hydrogenation. This new process has been tested on a multigram scale, with an improved overall yield of 60% and enhanced cost efficiency, while offering atom economy advantages. The low yield of the Claisen rearrangement and the use of costly and corrosive reagents in the previously reported synthesis were avoided.",10.1021/acs.oprd.5c00044,2025-04-28,0.6155750892651063
Journal of Organic Chemistry,Meroterpenoid Synthesis via Sequential Polyketide Aromatization and Cationic Polyene Cyclization: Total Syntheses of (+)-Hongoquercin A and B and Related Meroterpenoids,"(+)-Hongoquercin A and B were synthesized from commercially available trans, trans-farnesol in six and eleven steps, respectively, using dual biomimetic strategies with polyketide aromatization and subsequent polyene functionalization from a common farnesyl-resorcylate intermediate. Key steps involve Pd(0)-catalyzed decarboxylative allylic rearrangement of a dioxinone β,δ-diketo ester to a β,δ-diketo dioxinone, which was readily aromatized into the corresponding resorcylate, and subsequent polyene cyclization via enantioselective protonation or regioselective terminal alkene oxidation and cationic cyclization of enantiomerically enriched epoxide to furnish the tetracyclic natural product cores. Analogues of the hongoquercin were synthesized via halonium-induced polyene cyclizations, and the meroterpenoid could be further functionalized via saponification, hydrolytic decarboxylation, reduction, and amidation reactions.",10.1021/acs.joc.8b02095,2018-10-15,0.6155704560970879
Journal of Organic Chemistry,"Total Synthesis of <i>C</i>-Glycosylangucycline, Urdamycinone B, Using an Unprotected Sugar","The total synthesis of urdamycinone B ( 1 ), a prototypical member of the C -glycosylangucycline antibiotics, was achieved by a novel and effective strategy without any protecting group in the sugar moiety. The unprotected C -glycosyljuglone 6 was effectively synthesized by the aryl C -glycosidation of 1,5-naphthalenediol ( 16 ) with the totally unprotected d -olivose ( 8 ) and the subsequent regioselective photooxygenation of the resultant C -glycosylnaphthalenediol 17 . On the other hand, the diene 7 was prepared from 3-methyl-2-cyclohexen-1-one ( 9 ) in a short step via the cross-coupling of the vinyl triflate 20 and vinylbutyltin ( 21 ) and the Wittig reaction of the aldehyde 24 and the phosphine 25 . Finally, the regioselective Diels−Alder reaction of the unprotected C -glycosyljuglone 6 and the diene 7, followed by the regioselecitive introduction of the ketone function at the C1 position, led to the total synthesis of 1 .",10.1021/jo990648y,1999-08-21,0.615569439322582
Tetrahedron,A new class of condensing reagents for rapid internucleotide bond formation in the phosphotriester approach and preparation of n3-benzoylthymidine as a key intermediate in oligodeoxyribonucleotide synthesis,,10.1016/0040-4039(84)80055-6,1984-01-01,0.6155661827006732
Journal of Organic Chemistry,Lactone Pathway to Statins Utilizing the Wittig Reaction. The Synthesis of Rosuvastatin,"The first entry to statins via lactonized side chain is reported, exemplified by the synthesis of rosuvastatin. The key step is Wittig coupling of (2S,4R)-4-(tert-butyldimethylsilyloxy)-6-oxotetrahydro-2H-pyran-2-carbaldehyde and phosphonium salt of an appropriately functionalized pyrimidine heterocycle. One-pot deprotection and hydrolysis of the resulting 4-O-TBS rosuvastatin lactone provided rosuvastatin in high yield.",10.1021/jo101050z,2010-09-03,0.6155547614768273
Journal of the American Chemical Society,Total Synthesis of (+)-Cassaine via Transannular Diels−Alder Reaction,"A full account of the total synthesis of (+)-cassaine ( 1) using the transannular Diels-Alder (TADA) reaction as the pivotal construction is described. The strategy began from Evans' oxazolidine 8, the only chiral source used for the total stereochemical outcome of the target molecule. The key intermediate 3 was obtained from 8 in 10 steps in 40% overall yield. Following extensive optimization, the coupling of 3 on both ends with another densely functional partner 2 followed by TADA reaction on macrocycle 4 cleanly furnished the tricycle 5. The stereochemical outcome in 5 was expected via a least-energetic transition state T4. A stereoselective reduction, hydroboration, and methyl cuprate 1,4-addition along with a few other functional interconversions transformed 5 into the key intermediate 37. Final tethering of dimethylaminoethyloxycarbonyl along with epimerization at C8 and alcohol deprotection at C3 yielded the natural product 1.",10.1021/ja805097s,2008-09-26,0.6155547424028804
Journal of the American Chemical Society,Total Syntheses of (−)-Kopsifoline D and (−)-Deoxoapodine: Divergent Total Synthesis via Late-Stage Key Strategic Bond Formation,"Divergent total syntheses of (-)-kopsifoline D and (-)-deoxoapodine are detailed from a common pentacyclic intermediate 15, enlisting the late-stage formation of two different key strategic bonds (C21-C3 and C21-O-C6) unique to their hexacyclic ring systems that are complementary to its prior use in the total syntheses of kopsinine (C21-C2 bond formation) and (+)-fendleridine (C21-O-C19 bond formation). The combined efforts represent the total syntheses of members of four classes of natural products from a common intermediate functionalized for late-stage formation of four different key strategic bonds uniquely embedded in each natural product core structure. Key to the first reported total synthesis of a kopsifoline that is detailed herein was the development of a transannular enamide alkylation for late-stage formation of the C21-C3 bond with direct introduction of the reactive indolenine C2 oxidation state from a penultimate C21 functionalized Aspidosperma-like pentacyclic intermediate. Central to the assemblage of the underlying Apidosperma skeleton is a powerful intramolecular [4 + 2]/[3 + 2] cycloaddition cascade of a 1,3,4-oxadiazole that provided the functionalized pentacyclic ring system 15 in a single step in which the C3 methyl ester found in the natural products served as a key 1,3,4-oxadiazole substituent, activating it for participation in the initiating Diels-Alder reaction and stabilizing the intermediate 1,3-dipole.",10.1021/ja500548e,2014-02-05,0.6155536204774676
Journal of Organic Chemistry,Convergent Total Synthesis of Khafrefungin and Its Inhibitory Activity of Fungal Sphingolipid Syntheses,"A convergent total synthesis of khafrefungin, a novel inhibitor of fungal sphingolipid syntheses isolated from the fermentation culture MF6020, has been developed. Alkenylboronic acid 5 and alkenyliodide 6, key fragments for the total synthesis, were prepared from the corresponding achiral aldehydes using tin(II)-catalyzed and Zr(IV)-catalyzed asymmetric aldol reactions, respectively. The Suzuki coupling reaction of these two fragments was successfully performed to give 17 in good yield. Through the total synthesis, epimerization of the C4 position having a rather highly acidic proton did not occur, indicating that khafrefungin was under strict conformational constraints to prevent the epimerization process. This characteristic stability of khafrefungin has also been discussed using semiempirical calculation and synthesis. Finally, khafrefungin derivatives have also been synthesized, and their antifungal activities have been measured to obtain information on the structure--activity relationships.",10.1021/jo0158128,2001-07-17,0.6155439636318496
Journal of Organic Chemistry,General Entry to Asymmetric One-Pot [<i>N</i> + 2 + <i>n</i>] Cyclization for the Synthesis of Three- to Seven-Membered Azacycloalkanes,"Enantio- and diastereoselective one-pot synthesis of three- to seven-membered cis-azaheterocycles was achieved using a triggered asymmetric conjugate addition reaction of lithium amide with an enoate, followed by alkylation of the resulting lithium enolate with α,ω-dihaloalkane and N-alkylation. Isomerization of cis-azaheterocycles with a base yielded the trans-product, constituting a one-pot synthesis of cis-azacycles and a two-step synthesis of trans-azacycles. The four-step asymmetric synthesis of nemonapride highlights the general utility of the method.",10.1021/jo301495a,2012-08-15,0.6155426387039891
Tetrahedron,"A norbornyl route to cyclohexitols: stereoselective synthesis of conduritol-E, allo-inositol, MK 7607 and gabosines",,10.1016/s0040-4039(00)00409-3,2000-04-01,0.6155363917235669
European Journal of Organic Chemistry,"Toward the Synthesis of Tetrazino‐tetrazine 1,3,6,8‐Tetraoxide (TTTO): An Approach to Non‐annulated 1,2,3,4‐Tetrazine 1,3‐Dioxides","Abstract A novel approach for the synthesis of 6‐( tert ‐butyl‐ NNO ‐azoxy)‐5‐methylthio‐1,2,3,4‐tetrazine 1,3‐dioxide ( 1 ) was developed. This compound is likely to be a precursor of tetrazino‐tetrazine 1,3,6,8‐tetraoxide. The synthetic strategy consists of four steps: a synthesis of bis( tert ‐butyl‐ NNO ‐azoxy)methane, coupling of the latter with dimethyl nitrodithioimidocarbonate to give N ‐nitroimine 3 , O ‐alkylation of the latter to O ‐alkylated nitroenamine and its reaction with BF 3 · Et 2 O to afford tetrazine 1,3‐dioxide 1 . An X‐ray diffraction study of 1 was accomplished.",10.1002/ejoc.201500923,2015-08-19,0.6155312381623689
Angewandte Chemie International Edition,Enantioselective Total Synthesis of (−)‐Bisabosqual F via N‐Heterocyclic Carbene Catalyzed (4+2) Annulation,"In 2001, a family of meroterpenoids, the bisabosquals, were isolated from the Stachybotrys fungi during studies focused on the discovery of antifungals. Although they share biosynthetic precursors with more common Stachbotrys merotepenoids, their cyclization is reminiscent of the cannabinoid family thereby providing their unique densely functionalized benzopyran/benzofuran core. Despite interest in their total synthesis, to date only racemic bisabosqual A has been prepared, with the enantioselective total synthesis of any bisabosqual yet to be realized. Herein, we report the successful completion of the first enantioselective total synthesis of a bisabosqual with the 16-step synthesis of (-)-bisabosqual F. Key aspects include an enantioselective N-heterocyclic carbene (NHC) catalyzed (4 + 2) annulation to construct the D-ring; stereoinvertive cyclization at a tertiary alcohol to produce an advanced benzochromene; and late stage oxidative NHC-mediated lactonization to assemble the pentasubstituted aromatic.",10.1002/anie.202524461,2025-12-23,0.6155297237591156
Organic Process Research & Development,Synthesis of Nirmatrelvir: Development of a Scalable Cobalt-Catalyzed Cyclopropanation for Manufacture of the Bicyclic [3.1.0]Proline-Building Block,"Nirmatrelvir is a potent, selective, and orally bioavailable inhibitor of SARS-CoV-2 M pro . Herein, we report a scalable cyclopropanation to produce the bicyclic [3.1.0]proline derivative, which is one of the key starting materials for the synthesis of nirmatrelvir. To ensure a robust supply chain for this building block and meet the significant API demand, we needed to develop a synthetic process that was complementary to existing strategies. To achieve this goal, we used widely available and inexpensive raw material trans -(2 S,4 R )-4-hydroxy- l -proline as a starting material and implemented a recently reported cobalt-catalyzed gem -dimethylcyclopropanation at the manufacturing scale. Mechanistic studies led to the identification of potential catalyst decomposition pathways and provided insights into the key reaction parameters. This process was demonstrated to produce >200 kg of the bicyclic [3.1.0]proline derivative per batch and multi-metric ton quantities overall.",10.1021/acs.oprd.3c00251,2023-12-04,0.6155103195712041
Tetrahedron,Chiral base route to functionalised cyclopentenyl amines: formal synthesis of the cyclopentene core of nucleoside Q,,10.1016/j.tetlet.2004.10.043,2004-11-01,0.6155051436228869
Synthesis,"Diastereoselective Synthesisof γ-Amino Acids and Their Derivatives from Nitroethanevia Intermediacy of 5,6-Dihydro-4<i>H</i>-1,2-oxazinesBearing the CH<sub>2</sub>CH(CO<sub>2</sub>Me)<sub>2</sub> Substituentat C3","Stereoselective two-step reduction of available 2-[(5,6-dihydro-4H-1,2-oxazin-3-yl)methyl]malonates provides an efficient route to derivatives of different γ-amino acids. The mechanism and stereochemistry of the first step, reduction of the C=N bond with sodium cyanoborohydride, is discussed.",10.1055/s-0028-1083360,2009-02-11,0.6154919435146805
Chemical Science,Second-generation CK2α inhibitors targeting the αD pocket,"We describe the development of a <bold>CAM4712</bold> , a novel CK2α inhibitor which does not interact with the ATP binding site and shows improved properties over the first-generation inhibitor <bold>CAM4066</bold> .",10.1039/c7sc05122k,2018-01-01,0.6154666780801669
Tetrahedron,Synthesis of a hypothetical intermediate in the biosynthesis of the 13-methylbenzophenanthridine alkaloids corynoline and 14-epicorynoline and the B-secoprotoberberine alkaloid corydalic acid methyl ester,,10.1016/s0040-4039(00)84459-7,1986-01-01,0.6154648352359205
Journal of Organic Chemistry,Annulation Methods toward the Total Synthesis of Thermorubin: Construction of the AB and BCD Ring Systems,"New antibiotics are desperately needed to fight the growing threat of antimicrobial resistance. Thermorubin, a forgotten natural product, is one such candidate, as it binds to a novel site on the ribosome and uniquely disrupts both elongation and termination during protein synthesis. In this study, we report the synthesis of the AB and BCD ring portions of thermorubin in a 10% yield over six steps and an 8.9% yield over seven steps, respectively. The key disconnection for both systems involved identification of a symmetric nucleophilic donor synthon suitable for annulation with Michael acceptors within the core tetracycle─an unusual planar aromatic system. An activated form of this symmetric intermediate enabled a formal [4 + 2] cycloaddition with a 6-carboxy pyrone as well as traditional α-β-unsaturated ketones. Beyond advancing the total synthesis of thermorubin, these strategies offer broader utility for the construction of other complex heterocycles.",10.1021/acs.joc.5c01129,2025-07-29,0.6154583879260611
Journal of Organic Chemistry,Evolution of a Protecting-Group-Free Total Synthesis: Studies en Route to the Neuroactive Marine Macrolide (−)-Palmyrolide A,"A full account of our synthetic work toward the first total synthesis of the neuroactive marine macrolide (-)-palmyrolide A is described. Our first-generation approach aimed to unlock the unknown C(5)-C(7) stereochemical relationship via the synthesis of four diastereomers of palmyrolide A aldehyde, a known degradation product. When these efforts provided inconclusive results, recourse to synthesizing all possible stereocombinations of the 15-membered macrolide was undertaken. These studies were critical in confirming the absolute stereochemistry, yielding the first total synthesis of (+)-ent-palmyrolide A. Subsequent to this work, the first protecting-group-free total synthesis of natural (-)-palmyrolide A is also reported.",10.1021/jo301121f,2012-06-21,0.6154568384110979
Journal of Organic Chemistry,Convergent Synthesis of the NS5B Inhibitor GSK8175 Enabled by Transition Metal Catalysis,"A convergent eight-stage synthesis of the boron-containing NS5B inhibitor GSK8175 is described. The previous route involves 13 steps in a completely linear sequence, with an overall 10% yield. Key issues include a multiday S N Ar arylation of a secondary sulfonamide using HMPA as solvent, multiple functional group interconversions after all of the carbon atoms are installed (including a Sandmeyer halogenation), use of carcinogenic chloromethyl methyl ether to install a protecting group late in the synthesis, and an unreliable Pd-catalyzed Miyaura borylation as the penultimate step. We have devised an orthogonal approach using a Chan–Lam coupling between a halogenated aryl pinacol boronate ester and an aryl methanesulfonamide. This reaction is performed using a cationic Cu(I) precatalyst, which can be easily generated in situ using KPF 6 as a halide abstractor. High-throughput screening revealed a new Pd catalyst system to effect the penultimate borylation chemistry using simple monodentate phosphine ligands, with PCyPh 2 identified as optimal. Reaction progress analysis of this borylation indicated likely mass-transfer rate limitations under standard conditions using KOAc as the base. We have devised a K 2 CO 3 /pivalic acid system as an alternative, which dramatically outperforms the standard conditions. This new synthesis proceeds in eight stages with a 20% overall yield.",10.1021/acs.joc.8b02269,2018-10-19,0.6154548467082398
Synthesis,An Efficient Convergent Access to Spiroketal Segment of (+)-Spiroxaline Methyl Ether,"Starting from trimethylsilylacetylene, a facile synthesis of optically pure spiroketal unit of (+)-spiroxaline methyl ether has been described. The synthesis entails stepwise alkylation and acylation of an alkyne with two different readily available chiral building blocks followed by the reductive in situ regio- and stereoselective spiroketalization pathway.",10.1055/s-0030-1258456,2011-03-02,0.6154495677899641
Journal of Organic Chemistry,CuBr<sub>2</sub>-Mediated One-Pot Synthesis of Sulfonyl 9-Fluorenylidenes,"In this article, a high-yield method for the synthesis of sulfonyl 9-fluorenylidenes is described, which consists of a one-pot straightforward three-step synthetic route, including (i) CuBr 2 -mediated α-bromination of o -arylacetophenone, (ii) sequential nucleophilic substitution of the resulting α-bromo o -arylacetophenone with sodium sulfinate (RSO 2 Na), and (iii) the CuBr 2 -mediated intramolecular Friedel–Crafts cyclizative dehydration. A plausible mechanism is proposed and discussed. This protocol provides a highly effective regio- and stereoselective annulation via the formation of one carbon–carbon (C–C) bond and one carbon–sulfur (C–S) bond.",10.1021/acs.joc.0c00035,2020-05-08,0.6154282284076823
Tetrahedron,Synthesis of ring-expanded homologs of 3-amino pyranosides,,10.1016/j.tetlet.2022.153699,2022-02-23,0.6154237382781172
Tetrahedron,1-chloro-1-phosphirenes - a new synthesis from phosphaalkenes and carbenes,,10.1016/s0040-4039(00)99292-x,1989-01-01,0.6154139888140855
Tetrahedron,"1-Chloro-3-trimethylsilylcyclopropene--A new synthesis of 3,3′-bicyclopropenyl",,10.1016/s0040-4039(97)10317-3,1997-12-01,0.6154139888140855
Journal of the American Chemical Society,Total Synthesis of the Furaquinocins,"A viable synthetic route to the furaquinocin-class antibiotics is described. The key steps include (1) Co-complex mediated stereospecific 1,2-shift of an alkynyl group ( 9 → 6 ) to establish the C(2)−C(3) stereochemical relationship, (2) efficient construction of furanonaphthalene 20 from the sodium carboxylate derived from ester 19, and (3) stereoselective methylene transfer reaction to aldehyde 21 to establish the three contiguous stereogenic centers, C(2), C(3), and C(10). The stereodefined epoxide 23, thus obtained, served as a versatile intermediate in divergent syntheses of four congeners of this class of natural products, furaquinocins A ( 1a ), B ( 1b ), D ( 1d ), and H ( 1h ), by changing the vinylic nucleophiles.",10.1021/ja982403t,1998-10-30,0.6154071574137515
Journal of Organic Chemistry,Fragment Coupling Approach to Diaporthein B,"Pimarane diterpenes are produced by a diverse array of plants, fungi, and bacteria. Many members of this family possess antimicrobial and antiproliferative activities. The pimarane diterpenes are characterized by a tricyclic carbon scaffold comprising three fused six-membered rings and at least three quaternary centers. Here, we describe two convergent, fragment-based strategies toward the synthesis of diaporthein B ( 3 ), one of the most highly oxidized pimarane diterpenes. The first approach provided access to the tricyclic carbon scaffold of the target and featured a highly diastereoselective fragment coupling, a novel carbonylative Stille cross-coupling to directly access an α-hydroxyketone from a vinyl iodide, and a tandem aldol cyclization–deprotection cascade. The second route utilized a diastereoselective 1,4-addition of a silyloxyfuran to an unsaturated ketone, followed by an epoxidation–ring opening sequence, to access a highly oxidized intermediate containing two elaborated cyclohexane rings. The chemistry developed herein may ultimately be useful in an eventual synthesis of this class of natural products.",10.1021/acs.joc.2c02655,2023-02-03,0.6153963610445408
Tetrahedron,Pd2+-Promoted cyclization in linear triquinane synthesis total synthesis of (±)-hirsutene,,10.1016/s0040-4039(00)61738-0,1993-09-01,0.6153921499053654
Synthesis,"An Efficient Stereocontrolled Synthesis of Methyl (9<i>Z</i>,11<i>E</i>,13<i>S</i>)-13-Hydroxyoctadeca-9,11-dienoate (Methyl Coriolate)","All articles of this category An efficient synthesis of methyl (13 S )-coriolate ( S )- 1b is accomplished by the palladium-catalyzed coupling of (1 E ,3 S )-1-iodooct-1-en-3-ol [( S )- 3 ] with methyl dec-9-ynoate ( 4 ) followed by selective reduction of the enyne ( S )- 2 .",10.1055/s-1993-25867,1993-01-01,0.6153706171968325
Organic Letters,"Six-Step Synthesis of Alcyopterosin A, a Bioactive Illudalane Sesquiterpene with a <i>gem</i>-Dimethylcyclopentane Ring","Strategic pairing of ring openings and cycloisomerization provides rapid and efficient ""open and shut"" entry into sparsely functionalized illudalanes, as exemplified here in the context of a six-step synthesis of alcyopterosin A. Key steps include a tandem ring-opening fragmentation/olefination process for preparing a neopentyl-tethered 1,6-enyne, ring-opening olefination telescoped with alkyne homologation, and Rh-catalyzed oxidative cycloisomerization.",10.1021/acs.orglett.6b01665,2016-06-30,0.6153694222121265
Organic Letters,Enantioselective Synthesis of α-(Hetero)aryl Piperidines through Asymmetric Hydrogenation of Pyridinium Salts and Its Mechanistic Insights,"Enantioselective synthesis of α-aryl and α-heteroaryl piperidines is reported. The key step is an iridium-catalyzed asymmetric hydrogenation of substituted N-benzylpyridinium salts. High levels of enantioselectivity up to 99.3:0.7 er were obtained for a range of α-heteroaryl piperidines. DFT calculations support an outersphere dissociative mechanism for the pyridinium reduction. Notably, initial protonation of the final enamine intermediate determines the stereochemical outcome of the transformation rather than hydride reduction of the resultant iminium intermediate.",10.1021/acs.orglett.8b00067,2018-02-20,0.6153507793803691
Organic Letters,Synthesis of the [6–6–7–5–5] Pentacyclic Core of Calyciphylline N,"A new approach for the concise 11-step synthesis of the [6-6-7-5-5] BCDEF pentacyclic core of calyciphylline N is described. A type II [5 + 2] cycloaddition was employed to construct the strained BCD skeleton, which encompasses the challenging bicyclo[2.2.2] and bicyclo[4.3.1] ring systems. With a regio- and diastereoselective Lu's [3 + 2] cycloaddition, followed by intramolecular aldol cyclization and elimination, the desired [5-5]-fused EF ring system has been successfully installed, resulting in the complete carbocyclic skeleton of calyciphylline N.",10.1021/acs.orglett.4c00437,2024-03-04,0.6153411931889285
Synthesis,A Facile One-Step Synthesis of Methyl β-Oxodithiocarboxylates,,10.1055/s-1982-29907,1982-01-01,0.6153311032377269
Synthesis,"Improved Synthesis of 1,8-Diiodoanthracene and Its Application to the Synthesis of Multiple Phenylethynyl-Substituted Anthracenes","1,8-Diiodoanthracene was synthesized from 1,8-dichloroanthraquinone in three steps by improved procedures in 41% overall yield. Some anthracene derivatives carrying multiple phenylethynyl groups were synthesized from 1,8-diiodoanthracene and 4,5-diiodo-9-anthrone.",10.1055/s-2005-869999,2005-07-13,0.6153297401620184
Journal of Organic Chemistry,"Nucleophilic Addition of 1-Acetylindole Enolates to Pyridinium Salts. Stereoselective Formal Synthesis of (±)-Geissoschizine and (±)-Akagerine via 1,4-Dihydropyridines","Addition of the enolate derived from 1-acetylindole ( 3 ) to pyridinium salt 4b followed by acid-induced cyclization of the resulting 1,4-dihydropyridine 5b in the presence of lithium iodide gives tetracyclic 3,7-methano[1,4]diazonino[1,2- a ]indole 6b, which has subsequently been elaborated into the ( E )-ethylidene derivative 7b . From this compound is reported a stereocontrolled route to (±)-geissoschizine, involving closure of C ring by Pummerer reaction, methanolysis of the resulting pentacyclic lactam 12, and desulfurization. A similar synthetic sequence starting from the enolate of 3 and 2-fluoropyridinium salt 15b gives access to the pentacyclic dilactam 2, which had previously been converted to (±)-akagerine through opening of the piperidone (D) ring.",10.1021/jo9911894,1999-12-01,0.6153292544205264
Angewandte Chemie International Edition,Synthesis of<i>ent</i>‐Nanolobatolide,"Efficient and adaptable: The key steps in the total synthesis of ent-nanolobatolide, the enantiomer of the novel and potent neuroprotective agent, involve an oxidative ring expansion of (−)-menthone, a Nazarov cyclization, an intermolecular Diels–Alder reaction, and an intramolecular epoxide-opening reaction (see scheme). The two latter transformations provided evidence in support of the speculated biosynthetic pathway.",10.1002/anie.201100926,2011-04-06,0.6153291398229964
Tetrahedron,A one step synthesis of 4-oxo-Δ2-pyrrolines from iminoesters,,10.1016/s0040-4039(01)96757-7,1971-01-01,0.6153111115245029
Organic Letters,Substrate-Controlled Asymmetric Total Synthesis and Structure Revision of (−)-Bisezakyne A,"The first asymmetric total synthesis and subsequent structure revision of (-)-bisezakyne A, a Laurencia C15 acetogenin from Alpysia oculifera, has been accomplished. Our substrate-controlled synthesis of this oxolane natural product features a highly stereoselective ""protecting-group-dependent"" intramolecular amide enolate alkylation strategy for the synthesis of the key 9,10-trans-9,12-cis-10-hydroxytetrahydrofuran intermediate through ""nonchelate"" control. In addition, our synthesis determined the absolute configuration of the halogenated marine natural product.",10.1021/acs.orglett.6b02239,2016-08-23,0.6153024524185179
Organic Letters,Stereoselective Total Synthesis of Bioactive Marine Natural Product Biselyngbyolide B,A convergent strategy for the stereoselective total synthesis of biologically active marine natural product biselyngbyolide B has been developed. Key strategies of this synthesis include Jamison protocol of trans-hydroalumination/allylation for installation of C18-C23 olefin moiety and intramolecular Heck coupling for macrocyclization.,10.1021/acs.orglett.6b00713,2016-04-04,0.6152997158470123
Tetrahedron,"Synthesis of 6-(R)-hydroxy-7,9-octadecadiynoic acid, a HMG-CoA reductase inhibitor",,10.1016/s0040-4039(00)97286-1,1990-01-01,0.6152890876672273
Organic Letters,Convergent Synthesis of Tetrasaccharide Fragment of Cervimycin K,"A new synthetic approach toward oligosaccharides consisting only of 2,3,6-trideoxypyranoglycosides is reported. The key feature is highlighted by the convergent approach that allows the introduction of the aglycon moiety in the late stage of the synthesis. As an illustrative example, the tetrasaccharide portion of cervimycin K was prepared as cyclohexyl glycoside.",10.1021/acs.orglett.1c01404,2021-05-17,0.6152762348864309
European Journal of Organic Chemistry,Catalytic Asymmetric Synthesis of Mycolipenic and Mycolipanolic Acid,"Abstract The first asymmetric synthesis of mycolipenic acid and mycolipanolic acid by using an improved iterative procedure involving catalytic asymmetric conjugate addition of MeMgBr as the key step is described. Mycolipenic and mycolipanolic acid are obtained in 11 steps with perfect stereocontrol, and both acids are identical to their counterparts from natural sources.",10.1002/ejoc.200901120,2009-11-18,0.6152614422274665
Synlett,Stereoselective Synthesis of the C1-C12 Fragment of the Cytotoxic Macrolide FD-891,"A stereoselective synthesis of the C1-C12 fragment of the naturally occurring, cytotoxic macrolide FD-891, is described. The initial chirality was created via an asymmetric Evans aldol reaction. Two other asymmetric reactions, a Sharpless epoxidation and an aldehyde Brown allylation were further key steps of the ­synthesis.",10.1055/s-2004-835653,2004-11-08,0.6152599691880029
Chemical Science,Total synthesis of (−)-flueggenine A and (−)-15′- <i>epi</i> -flueggenine D,"-flueggenine D. The key step involved a novel reductive Heck dimerization strategy, utilizing a silyl-tethered enone coupling partner to ensure the desired reactivity and stereoselectivity. This dimerization method, combined with established chemistry explored en route to (-)-flueggenines C and D, offers a comprehensive synthetic approach for accessing all known RC-based oligomeric securinega alkaloids.",10.1039/d4sc07525k,2024-12-12,0.6152598362056056
Tetrahedron,A convenient and high yield synthesis of tertiary (amino) phosphines by transamination route,,10.1016/s0040-4039(00)82246-7,1988-01-01,0.615259824521777
Organic Process Research & Development,"Commercial Synthesis of (<i>S</i>,<i>S</i>)-Reboxetine Succinate: A Journey To Find the Cheapest Commercial Chemistry for Manufacture","The development of a synthetic process for ( S, S )-reboxetine succinate, a candidate for the treatment of fibromylagia, is disclosed from initial scale-up to deliver material for registrational stability testing through to commercial route evaluation and subsequent nomination. This entailed evaluation of several alternative routes to result in what would have been a commercially attractive process for launch of the compound.",10.1021/op200181f,2011-08-18,0.6152506597603403
Synthesis,The First Stereoselective Synthesis of a Dithiane Derivative of the C18 β-Diketodiene System Proposed for an Active Compound Isolated from Cantharellus cibarius (Chanterelle),"A stereocontrolled synthesis of a thioketal system that is a direct precursor of an active compound isolated from chanterelle was accomplished by using readily available methyl 11-[2-(2-oxoethyl)-1,3-dithian-2-yl]undec-9-ynoate as a key intermediate. The synthesis involves simple and straightforward reactions, such as addition of a lithiated alkyne to an aldehyde, alkyne hydrogenation using nickel boride, alcohol oxidation with Dess–Martin periodinane, and Z -to- E enone isomerization.",10.1055/s-0034-1379984,2015-01-27,0.6152498927361457
Synlett,Stereoselective Allyl AmineSynthesis via Enantioselective Addition ofDiethylzincand Sigmatropic Rearrangement; Synthesis of Lentiginosine,A new synthetic method for the preparation of allyl amine derivatives has been developed. The key steps of this method are enantioselective addition of diethylzinc (Soai protocol) and allyl cyanate-to-isocyanate rearrangement. Successful application of this procedure realized the synthesis of lentiginosine (6).,10.1055/s-2003-39314,2003-01-01,0.615241380261254
Organic Letters,"Expedient Construction of the ABEF Azatetracyclic Ring Systems of Lycoctonine-Type and 7,17-<i>seco</i>-Type C<sub>19</sub>-Diterpenoid Alkaloids","A synthetic strategy for the modeling construction of the highly bridged azatetracyclic ABEF ring system of numerous lycoctonine-type C19-diterpenoid alkaloids bearing a characteristic oxygenated quaternary center at C-7 has been successfully developed. The tetracyclic core was constructed rapidly from a readily prepared 6,7-bicyclic AB ring precursor through a 13-step sequence via an advanced tetracyclic N,O-acetal intermediate, which belong to another core structure of natural 7,17-seco-type alkaloids. The key step involves an SmI2-promoted intramolecular radical coupling reaction of an N,O-acetal with a carbonyl group, mimicking a plausible biogenetic transformation.",10.1021/ol500726x,2014-04-04,0.6152231278671493
Journal of Organic Chemistry,OSW Saponins:  Facile Synthesis toward a New Type of Structures with Potent Antitumor Activities,"[reaction: see text] OSW saponins, featuring a 16beta,17alpha-dihydroxycholest-22-one aglycon and an acylated beta-D-xylopyranosyl-(1-->3)-alpha-L-arabinopyranosyl residue attached to the 16-hydroxyl group, have recently been discovered from a group of lily plants, which show potent antitumor activities with a novel mechanism of action. This paper describes an aldol approach to the stereoselective construction of the 16alpha,17alpha-dihydroxycholest-22-one structure from 16alpha-hydroxy-5-androsten-17-ones and propionates. Elaboration of the aldol adducts toward OSW-1, involving installation of the isoamyl ketone side chain, inversion of the 16-hydroxyl configuration, and selective protection of the C22-oxy function, has been explored and accomplished. In particular, the present route was found convenient for the synthesis of OSW saponin analogues with a C22-ester side chain. Thus, the 23-oxa-analogue of OSW-1 (40) was prepared starting from the industrial dehydroisoandrosterone (1) in a linear eight-step sequence and in 26% overall yield. Analogues with a variety of modified side chains were prepared, via aldol condensation with propionates of varying length, thiopropionate, and acetate (for preparation of 68-75) or via aminolysis of the 22,16-lactone 26 (for preparation of the 23-N-analogues). Cross metathesis (CM) reaction was also found feasible for modification at the final stage from C22-allyl ester 70. Valuable structure-activity relationships (SAR), together with the practical synthetic approach, have thus been provided to set a new stage for further studies on this new type of antitumor structures.",10.1021/jo051536b,2005-11-05,0.6152122098928261
Journal of Organic Chemistry,Wittig Cyclization of ω-Hydroxy Hemiacetals: Synthesis of (+)-Aspicilin,"The polyhydroxylated 18-membered lichen macrolide (+)-aspicilin was synthesized in 12 steps and 17% yield (longest linear sequence) starting from d -mannose and ( S )-propylene oxide as the source of the stereogenic centers. Key steps were a palladium-catalyzed C sp3 X–C sp3 ZnX Negishi cross-coupling affording an ω-hydroxy hemiacetal which was macrocyclized via a domino addition–Wittig olefination reaction with the cumulated ylide Ph 3 PCCO. This synthetic approach also allowed a regioselective glycosylation of 6-OH of aspicilin with d -desosamine, a quick entry to chimeric macrolides with potential antibiotic activity.",10.1021/acs.joc.7b01702,2017-07-27,0.6152082406100645
Organic Letters,Total Synthesis of (−)-CP<sub>2</sub>-Disorazole C<sub>1</sub>,"The total synthesis of a bis-cyclopropane analog of the antimitotic natural product (-)-disorazole C(1) was accomplished in 23 steps and 1.1% overall yield. A vinyl cyclopropane cross-metathesis reaction generated a key (E)-alkene segment of the target molecule. IC(50) determinations of (-)-CP(2)-disorazole C(1) in human colon cancer cell lines indicated low nanomolar cytotoxic properties. Accordingly, this synthetic bioisostere represents the first biologically active disorazole analog not containing a conjugated diene or polyene substructure element.",10.1021/ol2015994,2011-07-08,0.6151995004838164
Organic Letters,Enantiospecific Approach toward Pentalenolactone,[reaction: see text] The enantiospecific assembly of the pentalenolactones' carbon skeleton was achieved in 17 steps and 16% overall yield from methyl alpha-D-glucopyranoside. The synthetic strategy relies on two highly efficient key steps: an exo-diastereoselective Diels-Alder reaction and a nonsymmetric ozonolysis.,10.1021/ol061390i,2006-07-27,0.6151986373972395
Journal of the American Chemical Society,Total Synthesis and Structural Confirmation of Chlorodysinosin A,"The first enantiocontrolled total synthesis of the marine sponge metabolite chlorodysinosin A is described. The structure and absolute configuration are identical to those of dysinosin A except for the presence of a novel 2S,3R-3-chloroleucine residue in the former. A concise stereocontrolled synthesis of the new chlorine-containing amino acid fragment was developed. An X-ray cocrystal structure of synthetic chlorodysinosin A with the enzyme thrombin confirms the structure and configuration assignment achieved through total synthesis. Within the aeruginosin family of natural products, chlorodysinosin A is the most potent inhibitor of the serine proteases thrombin, factor VIIa, and factor Xa, which are critical enzymes in the process leading to platelet aggregation and fibrin mesh formation in humans.",10.1021/ja0625834,2006-07-21,0.6151778982744283
Synlett,The Total Synthesis of Spermine Alkaloid Kukoamine Bimesylate,"The first total synthesis of kukoamine B bimesylate was completed from 1,4-diaminobutane dihydrochloride in 12 steps with a 11.4% overall yield, and all the steps could be carried out at a kilogram scale. The cyano groups were used as the precursor of amino groups to avoid the competitive reaction delicately. The aza-Michael addition reaction, amidation and hydrogenation of the cyano group sequence was streamlined as a general approach towards the synthesis of polyamine structures.",10.1055/s-0037-1610326,2018-11-14,0.6151778490143228
Angewandte Chemie International Edition,Enantioselective Synthesis of Tetrafluoroethylene‐Containing Monosaccharides,A Sharpless asymmetric dihydroxylation of the commercially available building block 1 affords the common chiral intermediate 2 for the synthesis of the fluorinated monosaccharides 3–5 (Bn=benzyl).,10.1002/anie.200460746,2004-10-20,0.6151745538063523
Journal of Organic Chemistry,An Enantioselective Route to Paeonilactone A via Palladium- and Copper-Catalyzed Reactions,"We herein report on a formal total synthesis of paeonilactone A involving palladium-, copper-, and enzyme-catalyzed reactions starting from 1,3-cyclohexadiene. The key step in the synthesis, a palladium(II)-catalyzed 1,4-oxylactonization of a conjugated diene, simultaneously introduces two of the oxygen substituents required for the target molecule. The synthesis also includes our recently developed copper(I)-catalyzed cross-coupling reaction between dienyltriflates with Grignard reagents, introducing one of the methyl groups present in the target molecule. This new approach toward paeonilactone A allows complete control of all four stereogenic centers and is the first enantioselective route toward paeonilactone A starting from an achiral substrate.",10.1021/jo991787i,2000-03-31,0.6151718116020096
Organic Letters,Synthesis of (−)-Paroxetine via Enantioselective Phase-Transfer Catalytic Monoalkylation of Malonamide Ester,"A new enantioselective synthetic method of (-)-paroxetine is reported. (-)-Paroxetine could be obtained in 15 steps (95% ee and 9.1% overall yield) from N,N-bis(p-methoxyphenyl)malonamide tert-butyl ester via the enantioselective phase-transfer catalytic alkylation and the diastereoselective Michael addition as the key steps.",10.1021/ol100928v,2010-05-25,0.6151405399930776
Synlett,Synthesis of Amaminol B,"The synthesis of the cytotoxic marine natural product amaminol B is described. Key steps include an organocatalytic intramolecular Diels-Alder reaction, an HWE olefination and a dia­stereoselective ketone reduction.",10.1055/s-2007-1000935,2008-01-01,0.6151244781003335
Organic Process Research & Development,Gram-Scale Synthesis of the C14–C23 Fragment of Eribulin,"Eribulin is a structurally simplified and completely synthetic analogue of macrocyclic ketone halichondrin B. In 2010, eribulin was approved by FDA for the treatment of metastatic breast cancer (MBC). Although several research groups have reported the synthetic efforts toward eribulin, it is still a challenge to prepare eribulin in a large scale due to its complex molecular architecture. Herein, we report a novel and efficient route to the C14–C23 fragment of eribulin from cheap l -arabinose.",10.1021/acs.oprd.2c00370,2023-02-06,0.6151223786859462
Tetrahedron,An improved synthesis of the antiviral acyclonucleoside 9-(4-hydroxy-3-hydroxymethylbut-1-yl)guanine,,10.1016/s0040-4039(00)99010-5,1985-01-01,0.6151103805989192
Journal of Organic Chemistry,"Synthesis of 8-Methoxy-1-methyl-1<i>H</i>-benzo[<i>d</i><i>e</i>][1,6]naphthyridin-9-ol (Isoaaptamine) and Analogues","8-Methoxy-1-methyl-1H-benzo[de][1,6]naphthyridin-9-ol, isoaaptamine, a PKC inhibitor isolated from sponge was synthesized. The synthesis parallels a synthesis of 8,9-dimethoxybenzo[de][1,6]naphthyridine, aaptamine, but uses a nitromethyl substituent as a precursor of the key 5-(2-aminoethyl)-1H-quinolin-4-one intermediate. The quinolone intermediates were prepared by thermolysis (220-240 degrees C) of anilinomethylene derivatives of Meldrum's acid. The quinolone intermediates were N-methylated prior to cyclization to the benzo[de][1,6]naphthyridine derivatives. Aaptamine and several analogues of aaptamine and isoaaptamine were prepared including 9-demethylaaptamine, 1-methyl-8-demethylaaptamine, 1-methylaaptamine, and the 8,9-methylenedioxy analogues of aaptamine and 1-methylaaptamine.",10.1021/jo001080s,2000-10-13,0.6151068134221523
Organic Letters,Asymmetric Synthesis of the DEFG Rings of Solanoeclepin A,"Starting from ( R )-seudenol, an asymmetric synthesis of the DEFG rings of solanoeclepin A has been developed. The key transformations include the substrate-controlled asymmetric Staudinger ketene cycloaddition and the intramolecular aldol reaction leading to the tricyclo[5.2.1.0 1,6 ]decane core of solanoeclepin A in 10 steps in the longest reaction sequence.",10.1021/acs.orglett.8b03742,2019-01-14,0.6150904566237569
Synthesis,Diastereoselective Synthesis of N-Alkylated Octahydroacridines via a Catalyst-Free SNAr Approach,"A three-step diastereoselective synthesis of N-alkylated octahydroacridines has been developed from inexpensive starting materials. Alkylation of cyclohexanone with 2-fluorobenzyl bromide, followed by nitration para to the aromatic fluoro substituent provided the cyclization substrate in 61% yield. Finally, a tandem reductive amination-S N Ar cyclization with NaCNBH 3 furnished the target compounds in 74–92% yields. X-ray and 1 H NMR studies permitted assignment of the stereochemistry of the B–C ring junction. The 3:1–10:1 preference for the cis -isomer was rationalized in terms of steric interactions in the imine reduction and a chair-like conformation for the cyclization. Hydride would be delivered to the molecular face opposite the fluoronitrobenzyl substituent at C-2 of the cyclohexanimine intermediate and the resulting amine would be positioned for addition to the S N Ar acceptor ring via a chair-like conformation.",10.1055/s-0034-1381033,2015-07-22,0.6150806391997206
Angewandte Chemie International Edition,Total Synthesis of (+)‐Haplophytine,"Advancing alkaloid synthesis: (+)-Haplophytine (see structure) was the target of a total synthesis featuring a highly stereoselective intramolecular Mannich reaction, Friedel–Crafts alkylation, oxidative rearrangement, and Fischer indole synthesis.",10.1002/anie.200902192,2009-07-03,0.6150702257354699
European Journal of Organic Chemistry,Unprecedented Formation of a Benzo[d]azepine by Acid-Catalyzed Cyclization of a Camphor-DerivedN-Formylenamine,"A convenient synthesis of (–)-N-styryl-N-[2-(1,7,7-trimethylbicyclo[2.2.1]hept-2-enyl)ethyl]formamide (2) was developed starting from natural (+)-camphor (3) via (–)-2-(bornen-2-yl)ethanol (6). Cyclization of the N-formylenamine 2 with the aid of 9-borabicyclo[3.3.1]non-9-yl triflate yielded a methanobridged octahydro-1H-benzo[d]azepine derivative.",10.1002/(sici)1099-0690(199902)1999:2<519::aid-ejoc519>3.0.co;2-r,1999-02-01,0.6150679850631385
Tetrahedron,Generation and cyclization of nitrilium ions from amides. Asymmetric synthesis of fused azabicyclics,,10.1016/s0040-4039(00)84451-2,1986-01-01,0.6150673887031105
Organic Letters,Stereodivergent Approach to the Asymmetric Synthesis of Bacillariolides:  A Formal Synthesis of <i>e</i><i>nt</i>-Bacillariolide II,"[reaction: see text] Asymmetric synthesis of densely functionalized bicyclic frameworks for entry into bacillariolides I/III and ent-bacillariolide II is reported. The key features are ring-closing metathesis of a pair of diastereomerically related dienes obtained through a stereodivergent route from a R-(+)-glyceraldehyde derivative, transformation of a nonstereoselective cyclopentene ester enolate alkylation process to a completely stereoselective one through alkylation of a bulky ester enolate with a bulky electrophile, and a remote silyloxymethyl group directed epoxidation.",10.1021/ol061377y,2006-07-20,0.6150639415705311
Tetrahedron,Efficient synthesis of trypsin inhibitor SFTI-1 via intramolecular ligation of peptide hydrazide,,10.1016/j.tetlet.2014.03.093,2014-03-27,0.615056731763474
Journal of the American Chemical Society,Enantioselective Total Synthesis of (+)-Peniciketals A and B: Two Architecturally Complex Spiroketals,"The enantioselective total syntheses of (+)-peniciketals A and B, two members of a family of architecturally complex spiroketals, have been achieved. Key synthetic transformations comprise Type I Anion Relay Chemistry (ARC) to construct the benzannulated [6,6]-spiroketal skeleton, a Negishi cross-coupling/olefin cross-metathesis reaction sequence to generate the trans -enone structure, and a late-stage large fragment union exploiting our recently developed photoisomerization/cyclization tactic.",10.1021/jacs.0c11424,2021-01-26,0.6150480219286977
Organic Process Research & Development,"An Efficient Large-Scale Process for the Human Leukocyte Elastase Inhibitor, DMP 777<sup>1</sup>","This report describes a new convergent, selective, and economical synthesis of DMP 777, 1 ending with the coupling of the chiral β-lactam half of the molecule ( 1 ) to the chiral amine as the isocyanate ( 2 ). Other steps involve the coupling of the β-lactam 3 to the phenolic moiety under phase-transfer conditions, followed by resolution of the resulting piperazine derivative using a chiral acid, and recycling of the undesired enantiomer also under phase-transfer conditions. The chiral amine 4 was produced efficiently starting from ( R )-α-methylbenzylamine and the corresponding butyrophenone.",10.1021/op015507o,2001-12-15,0.6150475522322865
Organic Letters,Total Synthesis of (−)-(α)-Kainic Acid via a Diastereoselective Intramolecular [3 + 2] Cycloaddition Reaction of an Aryl Cyclopropyl Ketone with an Alkyne,An enantioselective synthesis of (-)-(α)-kainic acid in 15 steps with an overall yield of 24% is reported. The pyrrolidine kainoid precursor with the required C2/C3 trans stereochemistry was prepared with complete diastereoselectivity via an unprecedented SmI2-catalyzed intramolecular [3 + 2] cycloaddition reaction of an aryl cyclopropyl ketone and an alkyne. Double bond isomerization was then employed to set the remaining stereochemistry at the C4 position en route to (-)-(α)-kainic acid.,10.1021/ol3008414,2012-05-03,0.6150415033924045
Journal of Organic Chemistry,Total Synthesis of (−)-Piericone D,"The total synthesis of (−)-piericone D, a potential antithrombotic dihydrochalcone featuring an [3.3.0] octane core, is reported. Salient features of our synthesis include a stereoselective β- O -glycosylation to install the asebogenin aglycone and a late-stage global deprotection followed by simultaneous lactonization. The convergent synthesis paved the way for further structure–activity relationship (SAR) studies of (−)-piericone D.",10.1021/acs.joc.4c00671,2024-05-31,0.6150411700490556
Journal of the American Chemical Society,"Utilization of 1-Oxa-2,2-(dimesityl)silacyclopentane Acetals in the Stereoselective Synthesis of Polyols","We have developed a route for the stereoselective synthesis of 1-oxa-2,2-(dimesityl)silacyclopentane acetals, intermediates in the synthesis of highly functionalized 1,3-diols. This route involves a diastereoselective conjugate addition reaction of a hydrosilyl anion, a subsequent diastereoselective enolate alkylation, and a fluoride-catalyzed intramolecular hydrosilylation reaction to afford the oxasilacyclopentane acetal. A highly selective nucleophilic substitution reaction, followed by oxidation of the C-Si bond, leads to the desired polyol.",10.1021/ja027335w,2002-10-01,0.6150383930721399
Synthesis,A Selective and Mild Synthetic Route to Dialkyl Phosphates,A very mild synthetic route to dialkyl phosphates is described. Reaction of the appropriate alcohol with PCl3 followed by treatment with pyridine and CCl4 afforded the corresponding trichloromethyl ester. Subsequent reaction with the triethylamine salt of acetic acid followed by hydrolysis of the formed mixed anhydride under very mild conditions afforded the dialkyl phosphates in high yield.,10.1055/s-2003-38074,2003-01-01,0.6150328606622022
Journal of the American Chemical Society,Total Synthesis of (+)-Mannolide B,"(+)-Mannolide B possesses an intriguing and complex 5/7/5/6/6/6-fused hexacyclic scaffold including two bridged-lactone moieties and nine contiguous stereocenters, and thus represents a formidable challenge for total synthesis. Herein, the evolution of a successful strategy for the synthesis of mannolide B is described. The 7/5 ring system of the 7/5/6/6 tetracyclic carbon skeleton was efficiently constructed by a ring-closing metathesis starting from commercially available (-)-methyl jasmonate. Attempts to access the 6/6 ring system were unexpectedly challenging. Initially, an intramolecular Diels-Alder reaction was designed; however, the desired cyclization precursor could not be obtained. Furthermore, a radical cascade cyclization was investigated and produced only one six-membered ring with poor stereoselectivity at C5. Finally, the 6/6 ring system was successfully generated through a Pauson-Khand reaction, followed by a highly regioselective Büchner-Curtius-Schlotterbeck reaction, enabling us to achieve the first total synthesis of (+)-mannolide B in 24 steps.",10.1021/jacs.4c12767,2024-12-17,0.6150307527783568
Organic Letters,"Total Synthesis of (−)-(6<i>S</i>,7<i>S</i>,8<i>S</i>,9<i>R</i>,10<i>S</i>,2‘<i>S</i>)-Membrenone-A and (−)-(6<i>S</i>,7<i>S</i>,8<i>S</i>,9<i>R</i>,10<i>S</i>)- Membrenone-B and Structural Assignment of Membrenone-C","[reaction: see text] (-)-(6S,7S,8S,9R,10S,2'S)-Membrenone-A and (-)-(6S,7S,8S,9R,10S)-membrenone-B were prepared in 11 steps (3% and 2.4% overall yield, respectively). Key steps included a tin(II)-mediated aldol followed by a syn selective reduction, giving the C7-C9 stereocenters, a second chain extending aldol coupling, and a p-TsOH-promoted cyclization/dehydration giving the common gamma-dihydropyrone precursor. We have thus established that synthetic (-)-(6S,7S,8S,9R,10S,2'S)-membrenone-A, (-)-(6S,7S,8S,9R,10S)-membrenone-B, and (-)-(6S,7S,8S,9R,10S)-membrenone-C are the enantiomers of the natural products.",10.1021/ol025674o,2002-04-19,0.6150279877916487
Tetrahedron,"Efficient method for the preparation of 2α,3β-dichcloro-4,4,10-trimethyl-decalin systems as a route for the synthesis of dichlorolissoclimide",,10.1016/s0040-4039(00)60473-2,1993-04-01,0.6150245069323992
Tetrahedron,Simple and highly diastereoselective synthesis of a 1β-methylcarbapenem key intermediate involving divalent tin enolates,,10.1016/s0040-4039(00)85301-0,1986-01-01,0.6150231601011665
Synlett,First Enantioselective Total Synthesis of the Angucyclinone-Type Antibiotic YM-181741,A simple and efficient strategy for angucyclinone antibiotics is described with the disclosure of first total synthesis of YM-181741.,10.1055/s-2007-973863,2007-03-26,0.6150046716902028
Organic Letters,Total Synthesis of Spirotryprostatin B via Asymmetric Nitroolefination,[reaction: see text] A total synthesis of spirotryprostatin B was accomplished via asymmetric nitroolefination as a key step.,10.1021/ol016999s,2001-12-27,0.6149976973548167
Journal of Organic Chemistry,Domino Ring-Opening Cyclization of Activated Aziridines with Indoles: Synthesis of Chiral Hexahydropyrroloindoles,"A highly enantioselective synthetic route to hexahydropyrrolo[2,3- b ]indoles via Lewis acid-catalyzed S N 2-type ring opening of activated aziridines with indoles having substitutions at 3- and other positions followed by cyclization in a domino fashion has been developed. Hexahydropyrrolo[2,3- b ]indoles have been detosylated in the same pot to afford the corresponding products with free NH group in excellent yields (up to 95%) and enantioselectivity (up to >99%).",10.1021/acs.joc.6b01731,2016-10-19,0.6149895391650058
Tetrahedron,"Diastereoselective route to (2R,5S)- and (2S,5S)-2-methyl-1,6-dioxaspiro[4.5]decane, a pheromone component of the wasp Paravespula vulgaris",,10.1016/s0040-4039(03)01716-7,2003-09-01,0.6149799688467066
Tetrahedron,"Synthesis of dephostatin, a novel protein tyrosine phosphatase inhibitor",,10.1016/0040-4039(94)88253-3,1994-10-01,0.6149739760336234
Organic Letters,A Novel Approach to 3-Methylindoles by a Heck/Cyclization/Isomerization Process,"A novel synthesis of 3-methylindoles from chlorotriflates through a Heck reaction, carbamate/aryl chloride coupling, and isomerization sequence is presented. The three-step sequence is highly efficient and general, enabling the regiocontrolled synthesis of substituted indoles in short order.",10.1021/ol902636v,2010-01-14,0.6149701499876028
European Journal of Organic Chemistry,Practical Syntheses of Both Enantiomers of the Conformationally Restricted GABA Analogue <i>cis</i>‐(2‐Aminocyclobutyl)acetic Acid,"Abstract Two efficient routes have been established for the preparation of both enantiomers of cis ‐(2‐aminocyclobutyl)acetic acid, a conformationally restricted analogue of GABA. Both procedures converged on the racemic N ‐ tert ‐butoxycarbonyl derivative of the target compound, which was resolved through chiral derivatization with an oxazolidinone auxiliary, which also allowed determination of the absolute configuration of the new compounds. The first route involved the homologation of cis ‐2‐aminocyclobutanecarboxylic acid, whereas the second route employed an intramolecular photocyclization protocol, which provided an expedient, cis ‐selective access to the lactam form of the target structure.",10.1002/ejoc.201402676,2014-09-25,0.6149662866187539
Tetrahedron,Improved approach to the enantioselective synthesis of (+)-neovibsanins A and B,,10.1016/j.tetlet.2025.155552,2025-03-22,0.6149646662277737
Synthesis,A Concise Total Synthesis of (S)-Zearalenone and Zeranol,"A convergent total synthesis of the naturally occurring, 14-membered macrolides (S)-zearalenone and zeranol has been achieved through application of the Diels-Alder reaction, Jacobsen kinetic resolution, Mitsunobu coupling, ring-closing metathesis, and hydrogenation as key steps.",10.1055/s-0030-1260058,2011-05-26,0.6149597020602943
Organic Letters,Total Synthesis of (+)-Prunustatin A: Utility of Organotrifluoroborate-Mediated Prenylation and Shiina MNBA Esterification and Macrolactonization To Avoid a Competing Thorpe–Ingold Effect Accelerated Transesterification,"A convergent total synthesis of (+)-prunustatin A is described through the assembly of two key fragments and a macrolactonization. Shiina MNBA couplings were used for the formation of each of the four ester bonds in the tetralactone ring, including the key macrocyclization which was essential to minimize competing Thorpe-Ingold accelerated transesterification. Other key steps included an organoboron-based prenylation using potassium prenyltrifluoroborate and a carbonyldiimidazole-mediated coupling to form the salicylamide.",10.1021/acs.orglett.8b02396,2018-08-30,0.6149512834910584
Journal of Organic Chemistry,"Total Syntheses of (±)-Deethylibophyllidine Using a Crisscross Annulation:  Ring Cleavage of Octahydroindolo[2,3-<i>a</i>]quinolizines Followed by Tandem Cyclizations of Octahydroazecino[5,4-<i>b</i>]indoles","The total synthesis of (+/-)-deethylibophyllidine (1) is described. Three different sequences provide this pentacyclic alkaloid using a common strategy involving a crisscross annulation. Key steps include (i) C/D ring cleavage of a 2-formyloctahydroindolo[2,3-a]quinolizine to obtain octahydroazecino[5,4-b]indoles, via either a chloroformate induced process or a quaternary ammonium salt formation followed by treatment with lithium, and (ii) a tandem process consisting of an intramolecular Pictet-Spengler double cyclization upon a beta-indole position of a 2,3-disubstituted indole to generate the quaternary spiro center of the pentacyclic skeleton of ibophyllidine alkaloids. Attempts to extend the procedure to the construction of the pentacyclic framework of (+/-)-ibophyllidine result in very low yield.",10.1021/jo980909o,1998-09-19,0.614949392692754
Synthesis,A Concise Synthesis of Atipamezole,"All articles of this category Atipamezole (1) , a potent α 2 adrenergic receptor antagonist, was synthesized in four steps from dibromide 2 and 2,4-pentanedione. atipamezole - 2-acetylindan - adrenergic - antagonist",10.1055/s-1995-3884,1995-02-01,0.6149489896750516
Tetrahedron,A practical approach for the synthesis of lactate dehydrogenase A inhibitor GNE-140,,10.1016/j.tetlet.2024.155395,2024-12-01,0.6149477205003755
Tetrahedron,Synthetic studies on fusicoccin A: Enantioselective synthesis of the C-ring fragment,,10.1016/j.tetlet.2024.155364,2024-11-12,0.61494168410117
Journal of the American Chemical Society,The First Asymmetric Total Syntheses of (+)-Lycorine and (+)-1-Deoxylycorine,"The first asymmetric total syntheses of (+)-1-deoxylycorine ( 2a ) and (+)-lycorine ( 2b ), the unnatural enantiomer of lycorine ( 1 ), are described. Construction of lactam 12, a key intermediate in the synthesis of both 2a and 2b, began by Birch reduction-alkylation of the chiral benzamide 3 with 2-bromoethyl acetate followed by ester saponification to give the 6-(2-hydroxyethyl)-1-methoxy-1,4-cyclohexadiene 6a in 96% yield as a single diastereomer. This material was converted to the radical cyclization substrates 11a and 11b . Both 11a and 11b gave 12 and the reduced enamide 11c on treatment with AIBN and Bu 3 SnH in refluxing benzene solution. Lactam 12 also was obtained by photocyclization of enamide 11c . The allylic alcohol unit characteristic of the C ring of the lycorine alkaloids was fashioned by a radical induced decarboxylation-epoxide fragmentation of the N -hydroxy-2-thiazoline ester 21b . The resulting (+)-2- epi -deoxylycorine ( 22 ) was subjected to Mitsunobu inversion followed by LiAlH 4 reduction to give (+)-1-deoxylycorine ( 2a ). The synthesis of (+)-lycorine ( 2b ) involved the conversion of 12 to allylic alcohol 32 followed by a Torssell rearrangement of 32 to give the rearranged allylic acetate 35 . Epoxidation of 35 with dimethyldioxirane gave 36a, which set the stage for a decarboxylation-epoxide fragmentation of carboxylic acid 36b to give 37 by photolysis of 36b in the presence of acridine and tert -BuSH. Reduction of 37 with LiAlH 4 gave (+)-lycorine ( 2b ).",10.1021/ja9606440,1996-01-01,0.6149387317068892
Synlett,Suzuki-Miyaura Coupling Based Enantioselective Synthesis of (+)-epi- Clausenamide and the Enantiomer of Its 3-Deoxy Analogue,"The first enantioselective synthesis of two biologically interesting close analogues of clausenamide, namely (+)- epi -clausenamide and (–)-3-deoxy- epi -clausenamide, was reported. Key steps of the synthesis included construction of the chiral pyrrolinone intermediates from d - and l -serine derivatives, introduction of the C4-phenyl by Suzuki–Miyaura coupling and establishment of the C6 configuration by a threo -selective Grignard reaction. Optimization of the key Suzuki–Miyaura coupling reaction was described in detail.",10.1055/s-0031-1290804,2012-04-26,0.6149317835134228
Journal of the American Chemical Society,A Convergent Total Synthesis of Hemibrevetoxin B,"A convergent biomimetic synthesis of hemibrevetoxin B from d-glucal and d-arabinose utilizes an electrophile-promoted cascade anti-Baldwin cyclization of an epoxy alcohol. The epoxy alcohol arises from a palladium-catalyzed coupling of a highly functionalized organozinc compound and an alkenyl iodide, which serve as two chiral building blocks of similar size and complexity. This first successful implementation of a cascade epoxy alcohol cyclization for the synthesis of marine polycyclic ether toxins proceeds in 39 steps and 4% overall yield.",10.1021/ja029225v,2003-06-06,0.6149306806989744
European Journal of Organic Chemistry,Asymmetric Synthesis of Potent and Selective σ<sub>1</sub> Receptor Ligands with Tetrahydro‐3‐benzazepine Scaffold,"Abstract A new strategy for the synthesis of tetrahydro‐3‐benzazepinones 6 by reductive amination of keto acid 3 and subsequent carbonyl diimidazole (CDI) mediated cyclization was developed. Use of enantiomerically pure ( R )‐1‐phenylethylamine led to the formation of diastereomeric lactams ( R α ‐ R )‐ 6d and ( R α ‐ S )‐ 6e in a 80:20 ratio. Diastereoselective alkylation of ( R α ‐ R )‐ 6d , BH 3 ‐mediated reduction and exchange of the N ‐phenylethyl substituent provided enantiomerically pure tetrahydro‐3‐benzazepines with various substituents in the 1‐, 3‐, and 4‐positions. High σ 1 affinity was achieved with a benzyl, cyclohexylmethyl, or 1‐phenylethyl moiety at the N‐atom. Whereas ( R )‐configuration of the N‐substituent is crucial for high σ 1 affinity, the configuration of the 3‐benzazepine ring system does not influence the σ 1 affinity considerably. Introduction of additional substituents in the 1‐position led to almost complete loss of σ 1 affinity. Potent σ 1 ligands show high selectivity against the σ 2 subtype and the NMDA receptor.",10.1002/ejoc.201200927,2012-09-12,0.6149301677578013
Synlett,Total Synthesis of (±)-Phaeocaulisin A Enabled Chemistry Innovation and Biological Discovery,"Abstract Guaianolide sesquiterpene natural products are of great biological and synthetic importance. Among them, phaeocaulisin A with a unique tetracyclic skeleton was isolated in 2013 and found to exhibit anticancer cell proliferation activity and anti-inflammatory activity. The first total synthesis of ( − )-phaeocaulisin A was achieved by Procter and coworkers in 2022. Two years later, we reported a total synthesis of ( ± )-phaeocaulisin A. The key steps of our total synthesis include a novel palladium-catalyzed cyclopropanol ring-opening carbonylative esterification to access a key γ-ketoester, a regio- and stereo-selective aldol cyclization to build the 7-membered carbocycle, and a cascade ketalization/lactonization to construct the tetracyclic skeleton. This Synpact article reflects our journey toward ( ± )-phaeocaulisin A, which also led to the discovery of an analogue with potent anticancer activity against triple negative or HER2+ breast cancer.",10.1055/a-2706-0821,2025-09-19,0.6149282890445326
Organic Letters,Enantioselective Synthesis of Isotopically Labeled Homocitric Acid Lactone,"A concise synthesis of homocitric acid lactone was developed to accommodate systematic placement of carbon isotopes (specifically (13)C) for detailed studies of this cofactor. This new route uses a chiral allylic alcohol, available in multigram quantities from enzymatic resolution, as a starting material, which transposes asymmetry through an Ireland-Claisen rearrangement.",10.1021/ol402802g,2013-11-01,0.6149127661170767
Journal of Organic Chemistry,New general asymmetric synthesis of versatile .gamma.-alkylated butenolides and its application to expeditious synthesis of the chiral Geissman-Waiss lactones useful for (+)-retronecine synthesis,A new strategy for general asymmetric synthesis of chiral butenolides 7a–h is established by utilizing excellent diastereocontrolled alkylation with chiral tin(II) enolate 10 at the γ-position of hydroxy butenolides 4a–h. An efficient utility of the chiral butenolides is exemplified with the expeditious synthesis of the optically pure Geissman-Waiss lactone derivatives 23a and 23b.,10.1021/jo00283a009,1989-10-01,0.6149033281606239
Organic Process Research & Development,Development of a Kilogram-Scale Chemical Process for a Chiral Spirocyclic Isoxazolone,"A short and scalable process for the facile synthesis of chiral spirocyclic isoxazolone 1 was developed and demonstrated on a multiple kilogram scale in four steps from a readily available starting material 8 . To achieve process sustainability and efficiency, we implemented a highly efficient catalytic asymmetric allylic alkylation and a telescopic chemical process. More than 160 kg of the spirocyclic isoxazolone 1 were produced as a crystalline solid by a simple operation with >99:1 er and 38% overall yield. The structure of 1 was further confirmed by single-crystal X-ray analysis.",10.1021/acs.oprd.4c00008,2024-02-21,0.6148958963284094
Synthesis,Diethylaminosulfur Trifluoride (DAST)-Mediated Intramolecular Benzannulation of o-Allylchalcones: Synthesis of 3-Fluorotetralins,"A concise route for the synthesis of 3-fluorotetralines is described, including: (i) NaBH4-mediated reduction of oxygenated o-allylchalcones and (ii) sequential DAST-mediated intramolecular annulation of the resulting alkenols. A plausible mechanism is proposed and discussed. This protocol provides highly effective regio- and stereocontrolled allyl-enone cross-coupling to construct two stereocenters and one E-configured styryl group.",10.1055/s-0037-1612419,2019-04-01,0.6148778460013016
Synlett,"An Enantioselective Organocatalytic Route to Chiral 3,6-Dihydropyridazines from Aldehydes","Here we describe a highly enantioselective organocatalytic synthesis of chiral 3,6-dihydropyridazines from achiral ­starting materials which proceeds with good yield via a one-pot ­procedure.",10.1055/s-2006-951486,2006-09-01,0.6148673387728784
Angewandte Chemie International Edition,Synthetic Studies on Pseudo‐Dimeric Lycopodium Alkaloids: Total Synthesis of Complanadine B,"Two approaches to the total synthesis of the dimeric Lycopodium alkaloid complanadine B have been achieved. In the first approach (see scheme; route 1), a keto lycodine unit is coupled to another lycodine unit whereas in the latter approach (route 2), selective oxygenation of one of two pseudo-benzylic positions is achieved.",10.1002/anie.201208571,2013-01-10,0.6148402832801882
Organic Letters,"Asymmetric Total Synthesis of Eupalinilide E, a Promoter of Human HSPC Expansion",)-(-)-carvone in 12 steps is reported with an overall yield of 20%. The key steps of the synthesis are a tandem Favorskii rearrangement-elimination reaction in the chromatography-free synthesis of carvone-derived 2-cyclopentene carbaldehyde and its catalyst-free stereospecific tandem allylboration-lactonization using recyclable trifluoroethanol as a promoter and solvent affording β-hydroxymethyl-α-methylene-γ-butyrolactone.,10.1021/acs.orglett.2c01684,2022-06-28,0.6148326692460204
Synlett,Synthesis of Ten Members of the Maradolipid Family; Novel Diacyltrehalose Glycolipids from Caenorhabditis elegans,The synthesis of ten members of the maradolipid family is described using a direct route starting from trehalose.,10.1055/s-0030-1260318,2011-09-19,0.6148326131899566
Organic Letters,"Total Synthesis and Structural Confirmation of Brevisamide, a New Marine Cyclic Ether Alkaloid from the Dinoflagellate <i>Karenia brevis</i>","The first total synthesis of brevisamide (1) has been accomplished in 21 linear steps starting from cis-but-2-ene-1,4-diol. A synthetic highlight is the Suzuki-Miyaura coupling between an ether ring fragment and a dienol side chain. This result confirmed the structure of 1 isolated from the dinoflagellate Karenia brevis.",10.1021/ol802426v,2008-12-09,0.614827280202734
Tetrahedron,"Directed methallylations as a synthetic route to 1,3-polyols",,10.1016/s0040-4039(98)00182-8,1998-04-01,0.6148168956685789
Organic Letters,"Stereoselective Synthesis of Hexahydroimidazo[1,2-<i>a</i>]quinolines via S<sub>N</sub>2-Type Ring-Opening Hydroarylation–Hydroamination Cascade Cyclization of Activated Aziridines with <i>N</i>-Propargylanilines","A novel synthetic approach for the construction of 1,2,3,3a,4,5-hexahydroimidazo[1,2- a ]quinolines in good yields (up to 75%) with excellent stereoselectivity (dr up to 94:6, ee up to >99%) under one-pot domino ring-opening cyclization (DROC) conditions has been developed. The DROC protocol proceeds through a Lewis acid catalyzed S N 2-type ring-opening of activated aziridines with N -propargylanilines followed by intramolecular cyclization comprising concomitant hydroarylation and hydroamination steps in a domino fashion.",10.1021/acs.orglett.0c02801,2020-09-28,0.6148088059497245
Tetrahedron,Scalable synthesis of a new enantiomerically pure π-extended rigid amino indanol,,10.1016/j.tetlet.2011.10.144,2011-11-01,0.614791583336388
Journal of Organic Chemistry,"A Formal Synthesis of Lavendamycin Methyl Ester, Nitramarine, and Their Analogues: A Povarov Approach",A convergent formal synthesis of lavendamycin methyl ester and synthesis of its analogues have been delineated through the Povarov approach. This protocol is also applied to the formal synthesis of nitramarine (3) in good yield.,10.1021/jo302389s,2012-12-10,0.6147819794781495
Synlett,A Unified Strategy for the Regiospecific Assembly of Homoallyl-Substituted Butenolides and γ-Hydroxybutenolides: First Synthesis of Luffariellolide,"The first synthesis of the antiinflammatory marine ­natural product luffariellolide has been achieved by a convergent pathway involving sp3-sp3 cross-coupling and silyloxyfuran oxyfunctionalisation as key steps. An illustration of the inherent ­flexibility of this strategy is provided by a simple synthesis of α,β-acariolide and its γ-hydroxylated derivative from a common silyl­oxyfuran precursor.",10.1055/s-2006-949641,2006-09-01,0.614776046931756
Synlett,Synthesis of a New Mutagenic Benzoazepinoquinolinone Derivative,"A novel mutagenic compound 1, isolated as a Maillard product from tryptophan and glucose, was synthesized using Larock’s quinoline formation, where addition of iodonium cation to an acetylene moiety of N-propargylaniline triggers subsequent intramolecular electrophilic aromatic substitution to afford quinolines. The key synthetic intermediate 14 was obtained in a good yield when iodonium chloride was employed as an initiator of Larock’s method. Conversion of 14 with another six steps, including annulation of a lactam ring and Curtius rearrangement, furnished the target molecule 1. The synthesized and isolated 1 were identical in comparison of physical and spectral data.",10.1055/s-0029-1217358,2009-06-12,0.6147463837719023
Journal of Organic Chemistry,"Stereoselective and Divergent Aza-Adenosine and Aza-Guanosine Syntheses from Xylofuranose, the Key Fragments of a STING Cyclic Dinucleotide Agonist","The stereoselective and divergent synthesis of two aza-nucleosides is reported. Starting from xylofuranose 9, aza-adenosine 2 was prepared in 13 steps and 7% overall yield, and aza-guanosine 3 was prepared in 13 steps and 7.8% overall yield. Compared to the original syntheses, some advantages of these new routes are significant yield improvement, overall step-count reduction, an optimized protecting group strategy, the development of a versatile platform for nitrogenous base incorporation, and the elimination of hazardous reagents (e.g., benzyl isocyanate, Et 3 N·HF).",10.1021/acs.joc.1c00984,2021-07-14,0.6147303971080825
Tetrahedron,The synthesis of an aminophosphonic acid converting enzyme inhibitor,,10.1016/s0040-4039(00)84366-x,1986-01-01,0.6147270253157819
Journal of Organic Chemistry,Chiral Pool Meets Chiral Catalysis: Eight-Step Convergent Total Synthesis of Anticancer Natural Lipid Mycalol,"An exemplary blend of chiral pool with chiral catalysis is exhibited in an eight-step (longest) convergent asymmetric total synthesis of mycalol, which is a promising anticancer natural lipid from a marine source. The polyhydroxy lipid is constructed by using four blocks, and two of which are derived from the chiral pool ( d -mannitol and d -gluconolactone) and the other two by chiral catalysis (Sharpless epoxidation and Keck allylation). Alkylation and metathesis were used to knit the blocks in an excellent display of a modular convergent eight-step synthesis. The modular excess will enable rapid analogue generation as revealed by the convenient synthesis of 4- epi -mycalol similarly in an eight-step sequence.",10.1021/acs.joc.3c02201,2023-11-27,0.6147262533545677
Synthesis,A Facile and Green Synthesis of a Naphthyridine Derivative: A Novel Hedgehog Pathway Modulator,"A green and highly efficient synthesis of a naphthyridine derivative, a novel hedgehog pathway modulator, in high yield and purity from inexpensive starting materials is described. The key step involves an acid-promoted aryl amination reaction of aniline with naphthyridine halides.",10.1055/s-0030-1258212,2010-08-13,0.6147210028336056
Journal of Organic Chemistry,First Total Synthesis of Gliomasolide C and Formal Total Synthesis of Sch-725674,"Syntheses of two 14-membered macrolides Sch-725674 and Gliomasolide C are described here. The first total synthesis of Gliomasolide C, the short synthesis of Sch-725674, and regioselective Wacker oxidation of internal olefin are the highlights of this disclosure. In addition, a key macrocycle with orthogonal functionalities was designed and synthesized on a gram scale for the generation of analogues.",10.1021/acs.joc.5b02318,2015-12-03,0.6147192237071205
Synlett,Ring-Rearrangement Metathetic Approach to Fused 6/5/6/5/6-Oxacyclic Ring System and Bipentalene Derivatives,Abstract We have developed a useful synthetic route to a 6/5/6/5/6-oxacyclic ring system and bipentalene derivatives from dimeric 7-oxonorbornene derivatives by using ring-rearrangement metathesis as a key step. This method provides access to fused oxacycles containing eight stereogenic centers in just three steps and to bipentalene derivatives in two steps only.,10.1055/a-1921-7296,2022-08-09,0.6147131460002534
Synlett,Total Synthesis of the Resorcylic Lactone-Based Kinase Inhibitor L-783277,All articles of this category (opens in new window),10.1055/s-2008-1078406,2008-06-01,0.6147047431322407
Tetrahedron,"Indium-mediated coupling of 3-bromopropenyl acetate with (S)-Garner aldehyde: a route to 1,4-dideoxy-1,4-l-iminoribitol",,10.1016/j.tetlet.2003.10.050,2003-11-24,0.6146876391764228
Synthesis,Reaction of Pyridoxal with Phenols: Synthesis of Novel 1-Aryl-Substituted Furopyridines,"A new method based on the acid-catalyzed reaction of pyridoxal with polyfunctional phenols has been developed for the synthesis of potentially biologically active 1-aryl-6-methyl-1,3-dihydrofuro[3,4- c ]pyridin-7-ols. Advantages of this method include a good yield of the target furopyridines and the use of readily available hydrochloric acid as a catalyst. The possibility of extending the proposed approach to nu­cleo­philes other than phenols was demonstrated by the synthesis of the known biologically active compound 1-(5-hydroxy-3-methyl-1-phenyl-1 H -pyrazol-4-yl)-6-methyl-1,3-dihydrofuro[3,4- c ]pyridin-7-ol hydrochloride (TM2002).",10.1055/s-0034-1378684,2014-12-15,0.6146867401311884
Tetrahedron,"Enantiospecific synthesis of (s)-4-amino-4,5-dihydro-2-furancarboxylic acid, a new suicide inhibitor of gaba-transaminase.",,10.1016/s0040-4039(01)81580-x,1984-01-01,0.6146864473686003
Organic Letters,Stereocontrolled Synthesis of the Northern Part of Potent Proteasome Inhibitor TMC-95A,"[reaction: see text]. A protected version of the northern part of TMC-95A, a potent and selective proteasome inhibitor, was synthesized with full stereochemical control. Highlights of this synthesis include (i) a (Z)-selective Mizoroki-Heck reaction to construct the oxyindole portion, (ii) a diastereoselective epoxidation, (iii) a 6-endo selective epoxide opening by Boc carbonyl group to establish the stereochemistry of C6, and (iv) a 1,3-elimination reaction of the L-allo-threonine derivative under Mitsunobu conditions to afford the (Z)-1-propenylamine.",10.1021/ol016303v,2001-08-11,0.6146845636396869
Journal of Organic Chemistry,Total Synthesis of (+)-Iresin,"The first asymmetric total synthesis of (+)-iresin (4), an historically important ent-Drimane sesquiterpene lactone, was realized from aldehyde 3 via cyclic orthoester 6 in 5 steps. Notable transformations in this synthesis include a tandem trifluoroperacetic acid (TFPAA)-mediated Baeyer-Villiger oxidation-olefin epoxidation-epoxy ester cyclization, regioselective Burgess dehydration, and regioselective Fétizon oxidative lactonization.",10.1021/acs.joc.5b00365,2015-04-23,0.6146825924931678
Journal of Organic Chemistry,Concise Synthesis of 2-Amino-4(3<i>H</i>)-quinazolinones from Simple (Hetero)aromatic Amines,"A novel and simple method of preparation of 2-alkylaminoquinazolin-4-ones with fused heteroaromatic rings from easily accessible (hetero)aromatic amines is described. The method is very efficient, and the 2-alkylaminoquinazolinone derivatives are obtained in three steps without chromatographic purification. The key step is the ring closure of the N-protected guanidine intermediates by intramolecular Friedel-Craft's type substitution.",10.1021/jo7026883,2008-02-22,0.614681782914519
Tetrahedron,A four-step synthesis of erythro-m-chloro-3-hydroxytyrosine ethyl ester enantiomerically pure,,10.1016/s0040-4039(98)00172-5,1998-04-01,0.614676228369563
Journal of Organic Chemistry,Synthesis of Trehazolin from <scp>d</scp>-Glucose,"Trehazolin (2) is a specific inhibitor of trehalase, an enzyme that cleaves the reserve carbohydrates of many insects. We describe a short and efficient synthesis of trehazolin (2) and trehazolamine (5) that mimics its hypothetical biosynthesis. Starting molecule for the synthesis of trehazolamine (5) is glucose from which three chiral centers are conserved during the reaction sequence. The remaining two chiral centers of trehazolamine (5) are formed stereoselectively in a reductive cyclization of ketooxime ether 16 and the reduction of oxime ether 18. The overall yield of trehazolamine (5) is 22% over 8 steps from 15. The synthesis of trehazolin (2) from trehazolamine (5) follows a known procedure and is achieved in 63% over 3 steps.",10.1021/jo980485y,1998-07-30,0.6146741978298746
European Journal of Organic Chemistry,Highly Efficient Synthesis of Ureas and Carbamates from Amides by Iodosylbenzene‐Induced Hofmann Rearrangement,"Abstract A simple and efficient method for the synthesis of 1,3‐disubstituted ureas and carbamates from amides by using iodosylbenzene as the oxidant is described. Symmetric and asymmetric ureas and carbamates can be prepared by this procedure in up to 98 % yield. Ureidopeptides can also be prepared in good yield by this method.",10.1002/ejoc.201101784,2012-02-13,0.614674046304833
Synlett,A Novel Approach to Stilbenoid Dendrimer Core Synthesis,"A new synthetic protocol for the one-pot, stereoselective synthesis of 1,3,5-tris[(E)-4-halostyryl]benzene and 1,2,4,5-tetrakis[(E)-4-halostyryl]benzene derivatives as stilbenoid dendrimer cores via palladium-catalyzed Hiyama cross-coupling of aryl tri- or tetrahalides with 1,3-bis[(E)-4-halostyryl]disiloxanes is described.",10.1055/s-0028-1083630,2008-11-12,0.6146705091025506
Journal of Organic Chemistry,Concise Synthesis of PM-94128 and Y-05460M-A,"The enantioselective total synthesis of PM-94128, a potent cytotoxin of microbial origin, was accomplished by a concise nine-step sequence of reactions in 14% overall yield from N-Boc-l-leucine. The synthesis of Y-05460M-A, a one-carbon lower homologue of PM-94128, was also achieved from N-Boc-l-valine by the same approach, which enabled its stereochemical determination.",10.1021/jo9014968,2009-09-01,0.6146637493033464
Journal of the American Chemical Society,Total Synthesis of (−)-Spinosyn A via Carbonylative Macrolactonization,"Spinosyn A (1), a complex natural product featuring a unique 5,6,5,12-fused tetracyclic core structure, is the major component of spinosad, an organic insecticide and an FDA-approved agent used worldwide. Herein, we report an efficient total synthesis of (-)-spinosyn A with 15 steps in the longest linear sequence and 23 steps total from readily available compounds 14 and 23. The synthetic approach features several important catalytic transformations including a chiral amine-catalyzed intramolecular Diels-Alder reaction to afford 22 in excellent diastereoselectivity, a one-step gold-catalyzed propargylic acetate rearrangement to convert 28 to α-iodoenone 31, an unprecedented palladium-catalyzed carbonylative Heck macrolactonization to form the 5,12-fused macrolactone in one step, and a gold-catalyzed Yu glycosylation to install the challenging β-forosamine. This total synthesis is highly convergent and modular, thus offering opportunities to synthesize spinosyn analogues in order to address the emerging cross-resistance problems.",10.1021/jacs.6b07585,2016-08-11,0.6146618115048444
Organic Letters,Convergent Synthesis of Geometrically Disassembling Dendrimers using Cu(I)-Catalyzed C−O Bond Formation,"The convergent synthesis of geometrically degradable dendrimers based on the 2,4-bis(hydroxymethyl)phenol subunit is presented. The key step of the synthetic scheme involves the CuI/3,4,7,8-tetramethyl-1,10-phenanthroline-catalyzed coupling of aryl iodides and alcohols. The synthesis and disassembly of these compounds is discussed.",10.1021/ol102081q,2010-10-06,0.6146541276840827
Journal of the American Chemical Society,Enantioselective Total Synthesis of (+)-Obtusenyne,"A total synthesis of the laurencia metabolite (+)-obtusenyne has been completed. The key steps include a Sharpless kinetic resolution and an asymmetric glycolate alkylation to establish the stereogenic centers adjacent to the ether linkage and a ring-closing metathesis reaction to construct the nine-membered ether without the aid of a cyclic conformational constraint. The synthesis was completed in 20 linear steps from commercially available 1,5-hexadiene-3-ol.",10.1021/ja029956v,2003-05-21,0.614647748609601
European Journal of Organic Chemistry,"Approaches to the Preparation of 4‐Benzyloxy‐2‐(α,α,α‐D<sub>3</sub>)methylphenol, a Building Block for Labeled δ‐Tocopherol, and a New Synthesis of <i>R</i>,<i>R</i>,<i>R</i>‐5‐D<sub>3</sub>‐α‐Tocopherol","Abstract Different routes are described for the synthesis of 4‐benzyloxy‐2‐D 3 ‐phenol, a key building block in the preparation of D 3 ‐δ‐tocopherol. Conditions for the improvement of Minami’s reduction are also given, allowing a straightforward route to the title compound and a new synthesis of R , R , R ‐5‐D 3 ‐α‐tocopherol in good yields, starting from widely available R , R , R ‐α‐tocopherol. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2004)",10.1002/ejoc.200400535,2004-11-15,0.6146459177812095
Synlett,Synthesis of Nepetoidin B,"The first synthesis of nepetoidin B in an overall yield of 17% was achieved in two steps through Baeyer–Villiger oxidation of commercially available 1,5-bis(3,4-dimethoxyphenyl)-1,4-pentadien-3-one with oxone to produce the tetramethylated nepetoidin B, followed by demethylation using boron tribromide.",10.1055/s-0036-1591556,2018-03-28,0.6146445732264006
European Journal of Organic Chemistry,"New Enantioselective Synthesis of (10R,11S)-(+)-Juvenile Hormones I and II","The (10R,11S)-(+)-juvenile hormones I (1) and II (2) were synthesized by Sharpless asymmetric dihydroxylations of methyl (2E,6E,10E)-7-ethyl-3,11-dimethyl-2,6,10-tridecatrienoate (4) and methyl (2E,6E,10E)-3,7,11-trimethyl-2,6,10-tridecatrienoate (5), respectively, as the key steps.",10.1002/1099-0690(200106)2001:11<2145::aid-ejoc2145>3.0.co;2-j,2001-06-01,0.6146411963371915
Organic Letters,Stereoselective Sequence toward Biologically Active Fused Alkylidenecyclobutanes,"Combining an efficient preparation of cyclobutenylmetal species, high-yielding cross-coupling reactions, and highly diastereoselective [4 + 2]-cycloaddition led to opening a new route toward the synthesis of fused alkylidenecyclobutanes containing up to five consecutive stereocenters. New complex architectures, analogues to protoilludane skeletons, were obtained in a very efficient manner and with a minimum number of steps starting from commercial sources and were tested for their cytotoxicity against leukemia cell lines HL60.",10.1021/acs.orglett.7b00724,2017-04-04,0.6146282589189951
Tetrahedron,Synthetic studies on neomarinone: practical and efficient stereoselective synthesis of the side chain,,10.1016/j.tetlet.2007.07.064,2007-07-17,0.614622777046236
Synlett,"A Concise Synthesis of 24,25-Dihydro-6-epi-Monanchosterol A","Abstract We report the first synthetic entry to a steroid with an unusual bicyclo[4.3.1]dec-3-en-10-one A/B ring substructure as a close structural analogue of the anti-inflammatory monanchosterols. Under optimized conditions, regioselective cis-dihydroxylation of the Δ5-double bond of 7-dehydrocholesterol and subsequent Criegee oxidation yields the corresponding 5,6-seco-steroid as a pure Z-isomer which upon treatment with K2CO3 in MeOH diastereoselectively affords 24,25-dihydro-6-epi-monanchosterol A through intramolecular aldol addition (cyclization). The developed three-step sequence proceeds in 17% overall yield without the need of any protecting group. The title compound was characterized by X-ray crystallography.",10.1055/a-1480-5225,2021-04-12,0.6146014975838238
Angewandte Chemie International Edition,Convergent Total Synthesis of Yaku'amide A,"Total synthesis of the anticancer peptide natural product yaku'amide A is reported. Its β-tert-hydroxy amino acids were prepared by regioselective aminohydroxylation involving a chiral mesyloxycarbamate reagent. Stereospecific construction of the E- and Z-ΔIle residues was accomplished through a one-pot reaction featuring anti dehydration, azide reduction, and O→N acyl transfer. Alkene isomerization was negligible during this process. These methods enabled a highly convergent and efficient synthetic route to the natural product.",10.1002/anie.202014238,2020-12-18,0.6146012248123625
Tetrahedron,Chiral synthesis of L-γ-carboxyglutamic acid (L-Gla),,10.1016/0040-4039(94)02418-b,1995-02-01,0.614596785334779
Tetrahedron,"Synthesis of P-chiral, phosphorothioic acid analogs of N-phospholeucinamide",,10.1016/s0040-4039(96)02107-7,1996-12-01,0.614596785334779
Journal of Organic Chemistry,"Stereoselective Synthesis of 7,11-Guaien-8,12-olides from Santonin. Synthesis of Podoandin and (+)-Zedolactone A","Photochemical rearrangement of hydroxy ester 2, easily obtained from santonin (1), afforded butenolide 4, a good starting material for the synthesis of 7,11-guaien-8,12-olides. Compound 4 has been transformed into compound 10, which has been used for the synthesis of podoandin (5) and (+)-zedolactone A (ent-6). Regioselective elimination of the acetyl group on C10 afforded directly podoandin (5). For the synthesis of ent-6, a hydroxyl group has been regio- and stereoselectively introduced at the 4alpha-position through the 3alpha,4alpha-epoxide 15. The basic hydrolysis of the 10-acetyl group in compound 18 took place with concomitant intramolecular conjugated addition of the alkoxide to the butenolide moiety to give ether 19. Cleavage of the 7,10-oxido bridge via the lactone enolate afforded (+)-zedolactone A (ent-6). This synthesis has allowed for the establishment of the absolute stereochemistry of natural zedolactone A as the enantiomer of our synthetic product.",10.1021/jo000927h,2000-09-09,0.6145789948434736
Synthesis,Synthesis of a Thymidine-Derived Acylsilane: A New Synthetic Intermediate towards Thymidine Analogues,"An efficient procedure was established to synthesize a thymidine analogue bearing an acylsilane function at the 5′-position, starting from thymidine in four steps and 58% overall yield. This compound proved to be a valuable intermediate for the synthesis of various nucleoside analogues with a one-carbon chain elongation at the 5′-position and a useful compound towards the construction of modified oligonucleotides.",10.1055/s-2006-942438,2006-06-26,0.6145730077126126
Organic Letters,"Synthesis and Structure of Preorganized, <i>C</i><sub>3</sub>-Symmetric Trilactam Scaffolds with Convergently Oriented (<i>S</i>)-Acetylthiomethyl Appendages","[reaction: see text] Efficient modular synthesis of conformationally preorganized, C(3)-symmetric trilactams is reported. The allyl acetate cyclization substrate was synthesized in five steps from Garner's L-serine-derived aldehyde. After chiral ligand-mediated palladium cyclization, the resulting vinyl hydropyran was transformed into the orthogonally protected amino acids for iterative coupling. The final macrolactamization was accomplished using EDCI/HOBt or HATU/HOAt under high dilution conditions.",10.1021/ol0261480,2002-06-01,0.6145667035294907
Synlett,An Improved Synthesis of the Phosphonic Acid Analog of Tryptophan,"All articles of this category An efficient and short synthesis of the phosphonic acid analog of tryptophan {[1-amino-2-(3-indolyl)]ethylphosphonic acid, 1 } from indole-3-acetic acid which utilizes a novel zinc-copper couple reduction of an oxime is described.",10.1055/s-1992-21461,1992-01-01,0.6145295902700935
Journal of Organic Chemistry,Diastereoselective Synthesis of 2-Phenyl-3-(trifluoromethyl)piperazines as Building Blocks for Drug Discovery,"The synthesis of enantiomerically pure cis- and trans-2-phenyl-3-(trifluoromethyl)piperazines is described. It involved, as the key step, a diastereoselective nucleophilic addition of the Ruppert-Prakash reagent (TMSCF3) to α-amino sulfinylimines bearing Ellman's auxiliary. This methodology allows an entry into hitherto unknown trifluoromethylated and stereochemically defined piperazines, key scaffold components in medicinal chemistry.",10.1021/jo500832j,2014-05-23,0.6145229199197174
Tetrahedron,"Asymmetric synthesis of chiral spirocyclanes: A new route to the optically active spiro[cyclopentane-1,1′-indan]-2,5-dione system",,10.1016/0040-4039(96)00126-8,1996-03-01,0.6145220497593538
Organic Letters,Modular Synthesis of Highly Substituted Pyridines via Enolate α-Alkenylation,"A novel methodology for the synthesis of highly substituted pyridines based on the palladium-catalyzed enolate α-alkenylation of ketones is presented; the formation of aromatic compounds is a new direction for this catalytic C-C bond forming reaction. In the key step, a protected β-haloalkenylaldehyde participates in α-alkenylation with a ketone to afford a 1,5-dicarbonyl surrogate, which then undergoes cyclization/double elimination to the corresponding pyridine product, all in one pot. The β-haloalkenylaldehyde starting materials can be obtained from the corresponding methylene ketone via Vilsmeier haloformylation. Using this concise route, a variety of highly substituted pyridines were synthesized in three steps from commercially available compounds.",10.1021/acs.orglett.5b01312,2015-06-18,0.6144981726881548
Angewandte Chemie International Edition,De Novo Synthesis of Furanose Sugars: Catalytic Asymmetric Synthesis of Apiose and Apiose‐Containing Oligosaccharides,"A de novo synthetic method towards apiose, a structurally unusual furanose, is reported. The key feature is sequential metal catalysis consisting of the palladium-catalyzed asymmetric intermolecular hydroalkoxylation of an alkoxyallene and subsequent ring-closing metathesis (RCM). This strategy enabled the efficient synthesis of various apiose-containing disaccharides and a unique convergent synthesis of trisaccharides.",10.1002/anie.201604199,2016-07-06,0.6144969113387327
Journal of Organic Chemistry,A Five-Step Synthesis of (±)-Tylophorine via a Nitrile-Stabilized Ammonium Ylide,The Stevens rearrangement of a nitrile-stabilized ammonium ylide is the key step of a very short and practical synthesis of the phenanthroindolizine alkaloid (±)-tylophorine. The method requires only five linear steps and is devoid of any protecting group manipulations.,10.1021/jo3011045,2012-07-11,0.6144801375033676
Tetrahedron,The thermolysis of benzyl cobaloximes: A new one step synthesis of 5-arylisoxazoles,,10.1016/0040-4039(96)01059-3,1996-07-01,0.6144567168278504
Journal of Organic Chemistry,Total Synthesis of (+)-Polyoxin J,"Stereoselective total synthesis of (+)-polyoxin J is described. The synthesis was achieved in a convergent manner by coupling protected thymine polyoxin C (19) and 5-O-carbamoyl polyoxamic acid 27 and subsequent removal of the protecting groups. The key steps of the synthesis of protected thymine polyoxin C involved the stereoselective electrophilic epoxidation of E-allyl alcohol 7 derived from isopropylidene D-ribose derivative 5, followed by regioselective epoxide opening of 8 and conversion of resulting azido diol 9 to protected thymine polyoxin C (19). Protected polyoxamic acid 27 was synthesized stereoselectively by utilizing Sharpless epoxidation of tartrate-derived allylic alcohol 20 followed by a regioselective epoxide ring opening with diisopropoxytitanium diazide.",10.1021/jo9822378,1999-03-27,0.6144554062377346
Angewandte Chemie International Edition,"A General Soft‐Chemistry Route to Perovskites and Related Materials: Synthesis of BaTiO<sub>3</sub>, BaZrO<sub>3</sub>, and LiNbO<sub>3</sub> Nanoparticles","Perovskite nanoparticles were obtained by treating alkali or alkaline-earth metals dissolved in benzyl alcohol with transition metal alkoxides, which is a novel and generally applicable route to nanosized perovskites and related materials. In the picture, the synthetic route to BaTiO3 nanocrystals is superimposed on a high-resolution TEM image of a single nanoparticle.",10.1002/anie.200353300,2004-04-16,0.614455068087025
Organic Process Research & Development,"Development of an Acyl Sulfonamide Anti-Proliferative Agent, LY573636·Na","The synthesis of 5-bromo-thiophene-2-sulfonic acid 2,4-dichlorobenzoylamide sodium salt on multikilogram scale is described. The initial clinical supplies were made using carbonyl diimidazole to converge the two fragments. A more efficient acid chloride process has been developed, which also provides better control of impurities and color throughout the synthesis.",10.1021/op800210x,2009-01-12,0.6144411087333973
Organic Process Research & Development,Integration of a Highly Selective Demethylation of a Quaternized Ergoline into a One-Pot Synthesis of Pergolide,"We have developed a high-yielding one-pot synthesis of pergolide ( 10 ) from dihydrolysergol ( 1 ), which was isolated as pergolide mesylate ( 6, Permax), a semisynthetic ergot alkaloid marketed for the adjunctive treatment of Parkinson's disease. The process involved the formation of quaternized amine intermediates, followed by a highly selective demethylation and thioether formation via thiomethoxide ion. A novel tandem chromatography procedure was used to remove closely related byproducts, which included an unexpected and unusual thiomethyl ether homologue of pergolide.",10.1021/op9600015,1997-01-01,0.6144398624530146
Organic Letters,Biocatalytic Enantioselective Oxidation of <i>N</i> -Acyl- <i>S</i> -Methyl Sulfenamides for the Asymmetric Synthesis of <i>S</i> -Methyl Sulfoximines,"High Resolution Image Download MS PowerPoint Slide Enantioenriched sulfinamides serve as key intermediates for the asymmetric synthesis of sulfoximines and other S(VI) pharmacophores. Enantioselective biocatalytic oxidation of an S -methyl sulfenamide to the corresponding S -methyl sulfinamide proceeds in good yield and >99:1 er. Its utility as a key chiral intermediate was demonstrated by stereoretentive S -arylation and S -alkylation as well as by the asymmetric synthesis of two S -methyl sulfoximine drug candidates, with S -methyl substitution notably present in most sulfoximine clinical candidates.",10.1021/acs.orglett.5c04701,2025-12-19,0.6144362744216673
Organic Process Research & Development,Efficient Synthesis of Impurity-C of Antimigraine Agent Rizatriptan Benzoate,"During the commercial manufacturing of antimigraine drug Rizatriptan benzoate, several impurities are reported to be formed. This present work demonstrates a convergent and short synthesis of the most critical impurity (C) of Rizatriptan, [2-(5-((1H-1,2,4-triazol-1-yl)methyl)-1H-indole-2-yl)- N, N -dimethylethanamine ( 1 )], recently reported in U.S. Pharmacopeia.",10.1021/op200284m,2012-02-21,0.6144325797839193
Synlett,Efficient Novel Synthesis of Bexaglifazolin and Its Glycol Salt With Minimal Impurities,"Abstract An efficient and novel process for the synthesis of the antidiabetic drug bexagliflozin using 5-iodo-2-chlorobenzoic acid as the starting material was described in detail to identify and eliminate the critical impurities that may form during the various steps of the synthetic process. The best reaction parameters, including temperature, stoichiometry, and reaction time, were systematically evaluated by analyzing the impurity profile at each stage of the synthesis. The process was carefully optimized to effectively control the formation of these critical impurities, which was a key factor in ensuring the successful synthesis of pure bexagliflozin.",10.1055/a-2616-5635,2025-05-20,0.6144316418279894
Tetrahedron,A short route for the construction of the tetracyclic ring system of silicine-methuenine alkaloids,,10.1016/0040-4039(96)00607-7,1996-05-01,0.6144313550476594
Journal of Organic Chemistry,A Practical and Efficient Synthetic Route to Dihydropipercide and Pipercide<sup>1</sup>,"Dihydropipercide 1 and Pipercide 2 are examples of hydrophobic insecticidal isobutylamide derivatives isolated from Piper Nigrum L . which have received synthetic attention over the past decade. Novel structural features combining the N -isobutyldieneamide array, found in related natural products such as Pellitorine, with the 3,4-methylenedioxyphenyl moiety, found in insecticide synergists including Piperonyl Butoxide and Sesamex, render these as attractive targets for synthesis. Although a variety of synthetic routes to related natural products have appeared in the literature, practical methods for the preparation of the title compounds were lacking. Convenient and convergent 10−11-step protocols were developed which provided access to gram quantities of the targets. Methyl 6-oxohexanoate 4 was prepared from cyclohexanone enol acetate 3 via a tandem ozonolysis, methanolysis, hydrolysis process. Subsequent olefination and olefin isomerization steps followed by further elaboration provided the targets 1 and 2 . Noteworthy features of this methodology include the convenient synthesis of oxoester intermediate 4 and the phenythio radical-induced olefin isomerization of intermediate 6 which afforded high yields of >99.5% E -olefin 13 . These are both somewhat uncommon but potentially useful processes which may find further application in organic synthesis.",10.1021/jo981039d,1998-08-29,0.6144280245384732
Journal of Organic Chemistry,Synthetic Approach to Analogues of the Original Structure of Sclerophytin A,"A route to analogues of the original structure of sclerophytin A is described. The beta-anomer of dideoxyribosyl nitriles 10a,b (prepared from glutamic acid) was converted into the methyl ketone 11. Addition of a silylated acetylide to 11 in diethyl ether/trimethylamine gave mainly 22a. Alkylation with methallyl halide and ozonolysis gave the ketone 24, which was then converted by hydrogenation and a second ozonolysis into the keto aldehyde 26. A two-step aldol process afforded the desired 3-pyrone 27 in good overall yield. However, several methods for the conversion of this enone 27 into the desired sclerophytin analogue 2 failed.",10.1021/jo016246j,2002-08-29,0.6144199772250922
Organic Letters,First Total Synthesis and Structural Reassignment of (−)-Aplysiallene,The first total synthesis of (-)-aplysiallene has been completed in 16 steps and features a key sequential Mukaiyama aerobic oxidative cyclization to prepare the fused bis-THF core. The original stereochemical assignment has been revised as shown.,10.1021/ol701797e,2007-08-01,0.6144197487169399
Tetrahedron,Total synthesis of hydroxystrobilurin A via Stille coupling,,10.1016/j.tetlet.2008.02.056,2008-02-15,0.6144184197677044
Journal of Organic Chemistry,Total Synthesis of (±)-Leporin A,An efficient synthesis of (+/-)-leporin A (1) has been developed using a tandem Knoevenagel condensation-inverse electron demand intramolecular hetero Diels-Alder reaction to construct the key tricyclic intermediate 3 from pyridone 5 and dienal 6 in one pot in 35% yield. Hydroxylation (71%) of 3 and methylation (77%) of the resulting hydroxypyridone 2 completed the first total synthesis of (+/-)-leporin A (1).,10.1021/jo952053i,1996-01-01,0.6144159550998449
Synlett,First Total Syntheses of (+)-Garvensintriol and (+)-5-epi-Garvensintriol,"A concise and efficient carbohydrate-based approach for the total syntheses of (+)-garvensintriol and (+)-5-epi-garvensintriol is described in nine and six steps with 20% and 37% overall yield, respectively, starting from a known intermediate. A sequence of Grignard-assisted lactol opening with terminal alkyne, stereoselective keto reduction and oxidative lactonization are the key reactions.",10.1055/s-0029-1219557,2010-02-26,0.6144079040522004
Organic Letters,A 7-Step Formal Asymmetric Total Synthesis of Strictamine via an Asymmetric Propargylation and Metal-Mediated Cyclization,"Herein is shown how a novel catalytic asymmetric propargylation of 3,4-dihydro-β-carboline, followed by a designed Au(I)/Ag(I)-mediated 6-endo-dig cyclization, can directly deliver the indolenine-fused methanoquinolizidine core of the akuammiline alkaloid strictamine in its native oxidation state, ultimately achieving a 7-step formal asymmetric total synthesis. Also demonstrated are how the cyclization products can rearrange into vincorine-type skeletons and a further use for the developed propargylation with the first catalytic asymmetric total synthesis of decarbomethoxydihydrogambirtannine.",10.1021/acs.orglett.6b03839,2017-02-13,0.6144064379112025
Synthesis,A New One-Pot Synthesis of Isoflavanones,,10.1055/s-1982-30095,1982-01-01,0.6143977965323406
Tetrahedron,"A new one-pot synthesis of silylated 1,3-dienes",,10.1016/0040-4039(90)87029-y,1990-01-01,0.6143977965323406
Synthesis,"A New, One-Pot Synthesis of Silylated Cyanohydrins",,10.1055/s-1982-29750,1982-01-01,0.6143977965323406
Tetrahedron,Synthesis of a key reactive unit for use in the divergent or convergent synthesis of carbosilane dendrimers,,10.1016/s0040-4039(98)00208-1,1998-04-01,0.6143923257118961
Journal of the American Chemical Society,Enantioselective Total Synthesis of Hyperforin,"A modular, 18-step total synthesis of hyperforin is described. The natural product was quickly accessed using latent symmetry elements, whereby a group-selective, Lewis acid-catalyzed epoxide-opening cascade cyclization was used to furnish the bicyclo[3.3.1]nonane core and set two key quaternary stereocenters.",10.1021/ja312150d,2012-12-28,0.6143643072114108
Synthesis,"A Practical Route for the Preparation of Bis(2,2,2-trifluoroethyl) 2-Oxoalkylphosphonates","A generally applicable, practical route was developed for the preparation of bis(2,2,2-trifluoroethyl) 2-oxoalkylphosphonates starting from the corresponding dimethyl 2-oxoalkylphosphonates. The three-step procedure contains mild and easily scaled up transformations such as trimethylsilylation, chlorination with oxalyl chloride, and trifluoroethylation; the overall yield is ca. 50%.",10.1055/s-0034-1380162,2015-02-25,0.6143619839387162
Journal of Organic Chemistry,"Enantioselective Synthesis of P-Chirogenic 1,2,3-Triazolobenzophospholes","An enantioselective synthesis of a new class of benzophosphole-based heterocycles bearing a fused triazole ring with enantioselectivities of ≤99% is reported. The key steps of the synthesis are based on an innovative stereospecific phosphinyl N → O migration of aminophosphine-boranes into phosphinites, followed by an intramolecular cyclization. Five X-ray structures of P-chirogenic triazolobenzophospholes and a gold(I) complex were established, for assigning absolute configurations, the stereochemistry of the reactions, and the placement of the triazole substituent at the syn position of the P center.",10.1021/acs.joc.4c01009,2024-07-17,0.6143617073615677
Organic Process Research & Development,Efficient Total Synthesis of Bilirubin IXα from Butyrolactone,"High Resolution Image Download MS PowerPoint Slide Bilirubin, a yellow pigment formed during the heme breakdown in the red blood cells, plays a central role in the physiological processes of vertebrates. It is the main component of Bovis Calculus (Bezoar), one of East Asia’s most valuable and often-used medicinal materials. Although the significance of bilirubin in human health has been extensively studied, its chemical synthesis has remained a challenging endeavor. This paper presents an efficient total synthesis of bilirubin on a 33 g scale in a minimum number of steps from inexpensive starting materials under very mild conditions. The synthetic route featured 11 steps from butyrolactone, resulting in 19% overall yield with 98.8% purity. The convergent synthesis overcomes limitations such as difficult chromatographic separation, high toxicity of selenium compounds, expensive rhodium catalysts, and isomerization byproducts. This new synthetic pathway makes it possible to industrially produce bilirubin on a large scale. The methine bridge configuration in the ring systems AB and CD was assigned as a Z-syn -periplanar conformer, as corroborated by single-crystal X-ray studies.",10.1021/acs.oprd.4c00122,2024-06-25,0.6143576087596601
Organic Letters,A Convergent Synthesis of the Tricyclic Core of the Dictyosphaeric Acids,"The first synthetic route to the tricyclic core of the dictyosphaeric acids has been established starting from readily available (S)-(-)-4-(tert-butyldimethylsilyloxy)cyclohexenone and involving 9 steps, including a ring-closing metathesis to produce a 13-membered macrolactone, and a doubly tethered intramolecular Michael addition.",10.1021/ol702887e,2007-12-21,0.6143486415916118
Journal of Organic Chemistry,A Novel Strategy for the Preparation of Naturally Occurring Phosphocitrate and Its Partially Esterified Derivatives,"A novel method for the synthesis of phosphocitrate (1, PC) starting from triethyl ester of citric acid and MeOPCl2 is described. The method is based on selective stepwise hydrolysis of ester moieties from the intermediate Me-O-P(O)(Cl)(Z) (Z = triethylcitrate), 4a, which also allows one to prepare partially esterified derivatives of PC with good yield and purity without chromatographic purifications.",10.1021/jo061709c,2007-01-18,0.6143484628962522
Organic Letters,A New and General Synthetic Pathway to <i>Strychnos</i> Indole Alkaloids:  Total Syntheses of (−)-Dehydrotubifoline and (−)-Tubifoline by Palladium-Catalyzed Asymmetric Allylic Substitution,"[see reaction]. A novel procedure for the synthesis of an indole skeleton was developed. Treatment of a cyclohexenol derivative having a silyloxymethyl group at the 2-position with N-tosyl-o-bromoaniline in the presence of Pd2dba3*CHCl3 and (S)-BINAPO gave compound 6a with 84% ee in 75% yield. Compound 6a was converted into 11, which was treated with Pd(OAc)2 and Me(2)PPh in the presence of Ag2CO3 to give indoline derivative 12. From 12, we succeeded in the total syntheses of (-)-dehydrotubifoline and (-)-tubifoline.",10.1021/ol0159571,2001-05-17,0.6143484341234392
Organic Letters,Asymmetric Total Synthesis of (+)-Verrubenzospirolactone and (+)-Capillobenzopyranol,"The first asymmetric total synthesis of (+)-verrubenzospirolactone ( 1 ), a distinctive highly fused benzosesquiterpenoid, characterized by a pentacyclic skeletal structure, is realized through a concise 10-step synthetic pathway with an impressive 22.8% overall yield. Notable highlights of this synthetic endeavor include (i) the introduction of a Ru-catalyzed ortho C–H activation step, (ii) the application of Pd-catalyzed asymmetric allylic alkylation to establish a pivotal stereocenter at C-3 with an excellent enantiomeric excess, (iii) B -alkyl Suzuki–Miyaura coupling to construct a Diels–Alder precursor, and, ultimately, (iv) the successful deployment of an intramolecular Diels–Alder reaction to complete the synthesis of (+)-verrubenzospirolactone without erosion of the enantiomeric excess.",10.1021/acs.orglett.4c00605,2024-04-01,0.6143453580829703
Journal of Organic Chemistry,"Concise Enantioselective Synthesis of 3,5-Dialkyl-Substituted Indolizidine Alkaloids via Sequential Cross-Metathesis−Double-Reductive Cyclization","An efficient stereoselective synthesis of two 3,5-dialkyl-substituted indolizidine alkaloids is reported. The convergent syntheses are based on a novel sequence of a cross-metathesis (CM) reaction of an alpha,beta-unsaturated ketone and a chiral homoallylic amine followed by a domino reaction involving hydrogenation, N-deprotection, and two diastereoselective reductive aminations. Our concept presents one of a few examples of a highly selective CM reaction in the synthesis of a natural product.",10.1021/jo0346095,2003-10-23,0.6143405731329196
Tetrahedron,A convergent synthesis of the macrolide core of migrastatin,,10.1016/j.tetlet.2006.06.082,2006-07-11,0.6143378175500167
Synlett,Palladium-Mediated Intramolecular C-O and C-C Coupling Reactions: An Efficient Synthesis of Benzannulated Oxazepino- and Pyranocarbazoles,"An efficient route towards the synthesis of benzannulated oxazepino- and pyranocarbazoles has been accomplished via palladium-catalyzed intramolecular C-O and C-C cross-coupling reactions, respectively.",10.1055/s-0030-1260965,2011-07-21,0.6143287427719012
Journal of Organic Chemistry,"A New General Method for the Asymmetric Synthesis of 4-Alkyl-3-aryl-1,2,3,4-tetrahydroisoquinolines","A highly enantioselective method for the synthesis of 4-alkyl substituted 1,2,3,4-tetrahydroisoquinolines is reported. The key step relies on the asymmetric synthesis of alpha-alkylarylacetic acids by alkylation of their corresponding amides employing (S,S)-(+)-pseudoephedrine as chiral inductor. Subsequent Friedel-Crafts acylation, stereocontrolled reductive amination and Pictet-Spengler cyclization affords the title compounds in excellent yields and enantioselectivities.",10.1021/jo982008l,1999-06-01,0.6143264231722908
European Journal of Organic Chemistry,A‐Ring‐Modified 2‐Hydroxyethylidene Previtamin D<sub>3</sub> Analogues: Synthesis and Biological Evaluation,"To investigate the biological profile of the previtamin form of vitamin D, we synthesized new analogues of 19‐ nor ‐1α,25‐dihydroxyprevitamin D 3 bearing a 2‐hydroxyethylidene moiety at the A‐ring. The target compounds were prepared by convergent synthesis using a Sonogashira coupling between an A‐ring enyne synthon and a CD‐ring/side‐chain vinyl triflate. We have demonstrated the versatility of shikimic acid as a starting material for the synthesis of the A‐ring precursors. The binding affinity to vitamin D receptor (VDR) and human vitamin D binding protein (hDBP), and the MCF‐7 cell antiproliferative activity were evaluated.",10.1002/ejoc.201601263,2016-11-03,0.6143225824638806
Synthesis,"A Synthetic Route to [1,2,4]Triazolo[1,5-a][4,1]benzoxazepines","All articles of this category A reaction sequence leading to the new title compounds is described, the key step of which is an intramolecular cycloaddition of nitrilimine to a nitrile group. The synthesis involves an intramolecular nitrilimine cycloaddition to the nitrile group",10.1055/s-1995-4135,1995-12-01,0.6143200783482359
European Journal of Organic Chemistry,"Cyclobutylidenecyclopropane: New Synthesis and Use in 1,3-Dipolar Cycloadditions − A Direct Route to Spirocyclopropane-Annulated Azepinone Derivatives","Cyclobutylidenecyclopropane (7) was prepared in multigram quantities by a new three-step sequence starting from ethyl cyclobutanecarboxylate (4) (39% overall yield). 1,3-Dipolar cycloadditions of phenyl- (9), pyridyl- (10), and the newly prepared (four steps, 43% overall yield) spirocyclic nitrone 11 onto 7 resulted in the regioselective formation of the corresponding adducts 15−17, with the spirobutane moieties adjacent to the oxygen atom in the oxazolidine rings, in 52, 84, and 48% yields, respectively. Under flash vacuum pyrolysis conditions, the cycloadducts 15−17 underwent thermal rearrangement with opening of the four-membered ring, to afford the spirocyclopropanated azepinones 21−23 in 32, 30, and 19% yields, respectively. In the case of 17, the indolizidinone 25 was also isolated (13% yield). Mechanistically this rearrangement is interpreted in terms of a cyclobutylmethyl-to-penten-5-yl radical rearrangement.",10.1002/1099-0690(200110)2001:20<3789::aid-ejoc3789>3.0.co;2-o,2001-10-01,0.6143195322516106
Organic Letters,"Sulfinimine-Mediated Asymmetric Synthesis of 1,3-Disubstituted Tetrahydroisoquinolines:  A Stereoselective Synthesis of <i>cis</i>- and <i>trans</i>-6,8-Dimethoxy-1,3-dimethyl- 1,2,3,4-tetrahydroisoquinoline","[reaction: see text] The highly diastereoselective addition of lateral lithiated o-tolunitriles to sulfinimines followed by treatment of the resulting sulfinamide with MeLi, hydrolysis, and reduction represents a concise new methodology for the asymmetric synthesis of 1,3-disubstituted tetrahydroisoquinolines.",10.1021/ol006654u,2000-11-01,0.6142997687898596
Organic Letters,Concise Total Synthesis of (+)-Luteoalbusins A and B,"The first total synthesis of (+)-luteoalbusins A and B is described. Highly regio- and diastereoselective chemical transformations in our syntheses include a Friedel-Crafts C3-indole addition to a cyclotryptophan-derived diketopiperazine, a late-stage diketopiperazine dihydroxylation, and a C11-sulfidation sequence, in addition to congener-specific polysulfane synthesis and cyclization to the corresponding epipolythiodiketopiperazine. We also report the cytoxicity of both alkaloids, and closely related derivatives, against A549, HeLa, HCT116, and MCF7 human cancer cell lines.",10.1021/acs.orglett.5b02059,2015-08-25,0.6142916939680261
Tetrahedron,Serendipitous synthesis of a ditwistane: a one-step access!,,10.1016/j.tetlet.2004.10.124,2004-11-12,0.6142856087997068
Angewandte Chemie International Edition,Exceptionally Simple Enantioselective Syntheses of Chiral Hexa- and Tetracyclic Polyprenoids of Sedimentary Origin,"Coupling between a sulfone and an acylsilane fragment (see below) constitutes the first step in the exceptionally short total syntheses of two chiral hexacyclic hydrocarbons isolated from Eocene Messel shale (Germany). Like the first step, subsequent steps also employ a powerful synthetic tactic: polycyclization of a specially constructed chiral, multiply unsaturated oxirane. TBS=tBuMe2Si.",10.1002/(sici)1521-3773(19980504)37:8<1126::aid-anie1126>3.0.co;2-0,1998-05-04,0.61428423706949
Journal of Organic Chemistry,Short and Efficient Asymmetric Synthesis of (−)-α-Conhydrine,The short and efficient synthesis of (-)-alpha-conhydrine was accomplished with 41% overall yield in seven steps and high diastereo- and enantioselectivity. The anti-stereochemistry of the two stereogenic centers has been confirmed by the single-crystal X-ray analysis of an intermediate.,10.1021/jo070760t,2007-06-08,0.6142814124870231
Organic Letters,Biomimetic Total Synthesis of Angelicoin A and B via a Palladium-Catalyzed Decarboxylative Prenylation-Aromatization Sequence,"Five-step total syntheses of angelicoin A and B from 2,2,6-trimethyl-4-dioxinone are reported using late stage biomimetic aromatization reactions via diketo-dioxinones as intermediates. In addition, with angelicoin A, this aromatization was coupled with a palladium-catalyzed decarboxylative prenylation in a one-pot sequence as the key step.",10.1021/ol202320m,2011-09-21,0.6142773322267779
European Journal of Organic Chemistry,Jatrophane Diterpenes: Preparation of the Western Fragment of Pl‐3,"Abstract Jatrophane diterpenes are structurally intriguing natural products with promising biological properties. Herein, the synthesis of the western fragment of the Euphorbiaceae constituent Pl‐3 starting from (1 R ,5 S )‐bicyclo[3.2.0]hept‐2‐en‐6‐one is described. Key steps in the sequence include a Baeyer–Villiger oxidation, an iodolactonization reaction, and the installation of the northern side chain through the addition of a lithiated vinyl bromide. The overall efficiency of the route is increased by taking advantage of latent symmetry.",10.1002/ejoc.201301616,2014-01-08,0.6142738108098188
Journal of the American Chemical Society,Total Synthesis of (−)-Calyciphylline N,"The total synthesis of the architecturally complex Daphniphyllum alkaloid (-)-calyciphylline N has been achieved. Highlights of the synthesis include a Et2AlCl-promoted, highly stereoselective, susbtrate-controlled intramolecular Diels-Alder reaction, a transannular enolate alkylation, an effective Stille carbonylation/Nazarov cyclization sequence, and a high-risk diastereoselective hydrogenation of a fully substituted conjugated diene ester.",10.1021/ja411539w,2013-12-09,0.6142542604086987
Journal of Organic Chemistry,Synthetic Studies on Et-743. Assembly of the Pentacyclic Core and a Formal Total Synthesis,"A formal total synthesis of the potent anticancer agent Et-743 is described. The tetrahydroisoquinoline core is stereoselectively constructed using a novel radical cyclization of a glyoxalimine. Further elaboration of this core rapidly accessed the pentacyclic core of Et-743, but a mixture of regiosisomers was obtained in the key Pictet-Spengler ring closure. A known advanced intermediate in the synthesis of Et-743 was intercepted, constituting a formal synthesis of the molecule.",10.1021/jo801159k,2008-08-08,0.6142442272372721
Organic Letters,First Enantiospecific Synthesis of the Antitumor Marine Sponge Metabolite (−)-15-Oxopuupehenol from (−)-Sclareol,"[reaction: see text] A new route toward puupehenone-related bioactive metabolites from (-)-sclareol, based on the palladium(II)-mediated diastereoselective cyclization of a drimenylphenol, is described. Utilizing this, the first enantiospecific synthesis of the antitumor and antimalarial (-)-15-oxopuupehenol, together with improved syntheses of (+)-puupehenone, (+)-puupehedione, and (+)-15-cyanopuupehenone, were accomplished.",10.1021/ol047332j,2005-03-15,0.6142145459915653
Organic Letters,Progress toward the Total Synthesis of Kalihinane Diterpenoids,"[see structure]. Studies toward the total synthesis of marine diterpenoids isolated from Acanthella sp., e.g., kalihinol A, are described. Efficient construction of the functionalized trans-decalin core (11) is achieved through intramolecular Diels-Alder cyclization followed by diastereoselective epoxidation and aziridination.",10.1021/ol015828k,2001-05-11,0.614213980001779
European Journal of Organic Chemistry,An Eleven‐Step Synthesis of Galanthamine from Commercially Available Materials,"Narwedine, an immediate precursor to the therapeutically valuable alkaloid (–)‐galanthamine, has been synthesised by engaging an iodinated isovanillin derivative in an intermolecular Mitsunobu reaction with a 2‐cyclohexen‐1‐ol derivative. The resulting aryl ether participated in an exceptionally efficient intramolecular Heck reaction to give a tetracyclic lactol after the hydrolysis of the primary cyclisation product. This last compound is an advanced intermediate associated with the Magnus synthesis of narwedine and could be elaborated to narwedine itself under reductive amination conditions. As a result, an eleven‐step synthesis of galanthamine has been established.",10.1002/ejoc.201601085,2016-10-13,0.6142088079923358
European Journal of Organic Chemistry,A Selective Synthesis of Fluorinated Cispentacin Derivatives,"Abstract A facile selective method has been developed for the synthesis of new fluorine‐containing cispentacin stereoisomers. Mono‐ and difluorinated cispentacin derivatives were synthetized from a bicyclic β‐lactam in five or six steps involving a regio‐ and stereoselective hydroxylation through iodooxazoline formation, followed by deoxygenation by fluorination. Starting from an enantiomerically pure bicyclic β‐lactam obtained by enzymatic resolution of the racemic compound, an enantiodivergent procedure allowed the preparation of both dextro‐ and levorotatory difluorinated cispentacins.",10.1002/ejoc.201402121,2014-05-08,0.6142078882825532
Tetrahedron,Electrochemical reduction of phthalyl chloride. A new route for the synthesis of 3-substituted phthalides,,10.1016/s0040-4039(00)84911-4,1986-01-01,0.6141986111502079
Organic Process Research & Development,An Improved and Scalable Process for Zafirlukast: An Asthma Drug,"An improved and scalable process for the large-scale production of zafirlukast (Accolate), an important drug for asthma, is discussed along with impurity and scale-up-related issues.",10.1021/op800137b,2008-12-19,0.6141957757865772
European Journal of Organic Chemistry,Synthesis of <i>trans</i>‐β‐Elemene,"Highly efficient syntheses of the anti‐cancer agent trans ‐β‐elemene have been achieved by using the readily available (±)‐limonene as starting material. The syntheses were achieved in only nine to eleven steps with good overall yields. The key step in these reaction sequences is a stereoselective radical cyclization, induced by titanocene chloride.",10.1002/ejoc.201800800,2018-08-29,0.614185162375291
Journal of Organic Chemistry,"Total Synthesis of (+)-Viridianol, a Marine-Derived Sesquiterpene Embodying the Decahydrocyclobuta[<i>d</i>]indene Framework","A total synthesis of the title sesquiterpene 4 is described that starts with the chiral, non-racemic cis-1,2-dihydrocatechol 10 obtained through the whole-cell biotransformation of p-iodotoluene. Compound 10 is elaborated over seven steps, including Negishi cross-coupling and intramolecular Diels-Alder (IMDA) cycloaddition reactions, to ketone 7 that engages in a photochemically promoted 1,3-acyl migration and so affording cyclobutanone 6. Compound 6 was converted over further steps into the title compound 4.",10.1021/acs.joc.8b02626,2018-10-25,0.6141803767944822
Journal of the American Chemical Society,Total Synthesis of Reblastatin,"Enantioselective total synthesis of reblastatin is described. The synthesis highlights hydrozirconation, transmetalation, aldehyde addition sequence to install E-trisubstituted olefin and C7 stereocenter, and the first use of an intramolecular Buchwald-like amidation reaction to close the 19-membered macrolactam.",10.1021/ja055384d,2005-10-06,0.6141669685874552
Synthesis,Efficient and Practical Synthesis of 5′-Deoxytubercidin and Its Analogues via Vorbrüggen Glycosylation,"An efficient and practical synthesis of naturally occurring marine nucleosides 5′-deoxytubercidins on a 10 gram scale in good overall yield is reported. The key step was the Vorbrüggen glycosylation of pyrrolo[2,3-d]pyrimidines with 5-deoxy-1,2,3-tri-O-acetyl-β-d-ribofuranose.",10.1055/s-0030-1259975,2011-03-30,0.6141651010675581
Tetrahedron,Asymmetric synthesis of (−)-4-epi-shikimic acid,,10.1016/s0040-4039(00)00225-2,2000-04-01,0.6141595772299442
Tetrahedron,Asymmetric synthesis of (+)-trachyspic acid,,10.1016/j.tetlet.2008.07.004,2008-07-07,0.6141595772299442
Tetrahedron,Asymmetric synthesis of evoninic acid,,10.1016/j.tetlet.2022.153747,2022-03-19,0.6141595772299442
Tetrahedron,"Asymmetric synthesis of (2S,4R)-4-hydroxypipecolic acid",,10.1016/s0040-4039(00)00460-3,2000-05-01,0.6141595772299442
Organic Letters,Synthesis of Diethynyltriptycene-Linked Dipyridyl Ligands,"[reaction: see text] An efficient route to a new family of dinucleating ligands has been developed. A convergent strategy to these ligands involved dual Sonogashira cross-coupling of 2,3-diethynyltriptycene with a variety of functionally diverse 5-bromopyridines. The resultant ligands were accessed in four steps and 40-50% overall yield from 1,2,4,5-tetrabromobenzene. Synthesis of an imidazole and a quinoline derivative by this method is also described.",10.1021/ol051700h,2005-09-23,0.6141526171061673
Organic Letters,First Application of Tunable Alkyl or Aryl Sulfinamides to the Stereoselective Synthesis of a Chiral Amine:  Asymmetric Synthesis of (<i>R</i>)-Didesmethylsibutramine ((<i>R</i>)-DDMS) Using (<i>R)</i>-Triethylmethylsulfinamide ((<i>R</i>)-TESA),"A highly diastereoselective addition of i-BuLi to a triethylmethylsulfinamide derived aldimine was used as the key step in the first asymmetric synthesis of (R)-didesmethylsibutramine, a metabolite of sibutramine for the potential treatment of CNS disorders. [reaction: see text]",10.1021/ol026699q,2002-10-18,0.6141522258802908
Journal of the American Chemical Society,Scalable Synthesis of Cyclocitrinol,"A 10-step synthesis of the C25 steroid natural product cyclocitrinol from inexpensive, commercially available pregnenolone is reported. This synthesis features a biomimetic cascade rearrangement to efficiently construct the challenging bicyclo[4.4.1] A/B ring system, which enabled a gram-scale synthesis of the bicyclo[4.4.1] enone intermediate 18 in only nine steps. This work also provides experimental support for the biosynthetic origin of cyclocitrinol.",10.1021/jacs.8b06444,2018-07-15,0.6141493440133374
Synlett,Asymmetric Radical Cyclization Induced by a Matched Pair of Chiral Auxiliaries: Synthesis of a Chiral 1β-Methylcarbapenem Key Intermediate,All articles of this category The chiral 1β-methylcarbapenem key intermediate 1 was synthesized using an asymmetric radical cyclization of N -vinylic α-bromo amide 16 bearing a matched pair of chiral auxiliaries as a key step. asymmetric induction - 1β-methylcarbapenem - Mitsunobu reaction - radical cyclization - ruthenium tetroxide oxidation,10.1055/s-1995-5144,1995-09-01,0.614144974167057
Tetrahedron,Selective ozonolysis of methyl trans-communate. Synthesis of drimanes,,10.1016/s0040-4039(01)80608-0,1989-01-01,0.614139952932397
Tetrahedron,Studies directed toward the total synthesis of tetronolide 2. A stereoselective route to the racemic cyclohexene subunit,"A short stereoselective sequence is described for the preparation of the racemic form of the highly functionalized cyclohexene derivative 2 which comprises the upper segment of tetronolide (1), the aglycone of the antitumor tetrocarcins. A key element of this route is rapid assembly and intramolecular cycloaddition of the trienyl enol pyruvate 4, which achieves complete control over regiochemistry and good stereochemical control.",10.1016/s0040-4039(00)79872-8,1991-08-01,0.6141279602781999
Organic Letters,Expedient Enantioselective Synthesis of Cermizine D,"An efficient enantioselective synthesis of cermizine D has been developed that exploits the use of a common intermediate to access over 85% of the carbon backbone. Key steps include an organocatalyzed heteroatom Michael addition, a diastereoselective alkylation with α-iodomethyl phenyl sulfide, a conjugate addition to a vinyl sulfone species, and a sulfone coupling/desulfurization sequence to join the two major subunits.",10.1021/ol300342n,2012-02-28,0.6141277556777787
European Journal of Organic Chemistry,A Formal Synthesis of Herboxidiene/GEX1A,Abstract A formal synthesis of herboxidiene/GEX 1A is described. This approach demonstrates successful application of the Prins cyclization for the construction of the tetrahydropyran core of the target molecule. The chirality of the side chain has been established through the Sharpless asymmetric dihydroxylation and Evan's alkylation. The olefin cross‐metathesis was applied to couple both key fragments.,10.1002/ejoc.201402235,2014-06-03,0.6141276076274074
European Journal of Organic Chemistry,Stereoselective Total Synthesis of Attenols A and B,"Abstract A highly stereoselective total synthesis of attenols A and B is described. The salient features of this synthesis are the utilization of a reductive radical cyclization strategy for methyl center creation, a Prins cyclization/reductive opening cascade for anti ‐1,3‐diol motif generation, and a double alkylation tosylmethyl isocyanide (TosMIC) strategy to construct the spiro acetal segment.",10.1002/ejoc.201300623,2013-08-08,0.6141223209853389
Organic Letters,Synthesis of a Novel Conformationally Locked Carbocyclic Nucleoside Ring System,"[reaction: see text] A fast and efficient synthetic route to novel Northern locked carbocyclic nucleosides (as precursors of carbocyclic locked nucleic acids or cLNAs) is described. The target nucleoside with a oxabicyclo[2.2.1]heptane ring system was prepared from a simple starting material, diethyl malonate. Ring closure by intramolecular O-alkylation provided the target ring system as the major isomer over the [3.2.0] oxetane system. The adenine moiety was introduced through a reactive triflate after inversion of the stereochemistry of the corresponding alcohol by oxidation and reduction.",10.1021/ol034326z,2003-04-18,0.6141136534596758
Synthesis,Total Synthesis of Bongkrekic Acid via Sequential Suzuki-Miyaura Coupling Reactions,"An efficient total synthesis of (+)-bongkrekic acid, a potent apoptosis inhibitor, has been accomplished by employing a convergent strategy based on the Suzuki-Miyaura coupling of three fully functionalized segments.",10.1055/s-0029-1216928,2009-08-07,0.6141103212670255
Organic Letters,Synthesis of Eukaryotic Translation Elongation Inhibitor Lactimidomycin via Zn(II)-Mediated Horner–Wadsworth–Emmons Macrocyclization,An enantioselective synthesis of potent eukaryotic translation elongation inhibitor lactimidomycin has been accomplished in 21 linear steps. This synthesis features a Zn(II)-mediated Horner-Wadsworth-Emmons reaction that could be executed on a large scale to provide the highly strained 12-membered lactimidomycin macrolactone.,10.1021/ol401186f,2013-06-03,0.6141062210285458
European Journal of Organic Chemistry,Chiral Synthons from the Iridoid Glucoside Antirrhinoside − Synthesis of a Carbocyclic Homonucleoside Analogue,"The synthetic modification of the natural cyclopentanoid monoterpene glucoside antirrhinoside is reported. Some stereoselective modifications have been performed on the bicyclic iridoidic ring, resulting in opening of the dihydropyran ring. A series of chiral synthons having a highly oxygenated cyclopentanoid ring has been prepared, which could be used in the synthesis of nucleoside analogues. We describe herein the synthesis of an acyclovir derivative (DA-146) as an example.",10.1002/1099-0690(200111)2001:21<4061::aid-ejoc4061>3.0.co;2-3,2001-11-01,0.6140985085571874
Tetrahedron,A new total synthesis of (±)-clavulanic acid,,10.1016/s0040-4039(01)86869-6,1979-01-01,0.614089137731217
Organic Process Research & Development,Multigram Synthesis of Tetrasubstituted Dihydrobenzofuran GSK973 Enabled by High-Throughput Experimentation and a Claisen Rearrangement in Flow,"This article describes two routes toward the synthesis of cis or trans C2,3,5,7-tetrasubstituted dihydrobenzofurans as potent and selective bromodomain and extra-terminal BD2 inhibitors, followed by the optimization of the synthesis of the lead molecule GSK973 to support pre-clinical efficacy and safety studies. The use of flow chemistry for a Claisen rearrangement, extensive optimization of the fluorination step, and high-yielding aminocarbonylation were key to generate the required 50 g of material. The identified new route also represents a robust starting point for further optimization.",10.1021/acs.oprd.1c00422,2022-01-24,0.6140839708216992
Synlett,Enantioselective Synthesis of Sulindac,"All articles of this category A highly enantioselective synthesis of Sulindac, a non-steroidal anti-inflammatory, is reported using the asymmetric Kagan sulfoxidation as key step. asymmetric sulfur oxidation - sulindac - asymmetric synthesis - sulfoxides - isomerizations",10.1055/s-2001-9722,2001-12-31,0.6140807568898808
Synthesis,An Improved Synthesis of Hydroxyindoles,"An improved synthetic procedure for the synthesis of 6- and 7-hydroxyindoles is described. In this method, the addition of two chlorine atoms in 1-benzyloxy-4,5-dichloro-2-nitrobenzene (3) and 1-benzyloxy-2,6-dichloro-3-nitrobenzene (9) facilitated the subsequent cyanomethylation step to give substituted cyanomethyl-dichloronitrobenzenes 4 and 10, leading to an overall increase in the yield of the hydroxyindoles 6 and 12.",10.1055/s-2004-834924,2004-01-01,0.6140772742259578
Journal of Organic Chemistry,Total Synthesis of Lacosamide,"Total synthesis of anticonvulsant amino acid, lacosamide, is reported. The key step is stereospecific allyl cyanate-to-isocyanate rearrangement, which proceeds with chirality transfer. The enantiopure starting material for the rearrangement step was accessed from ethyl L-lactate.",10.1021/jo500857t,2014-06-05,0.6140705463214516
Organic Process Research & Development,Use of a Titanium Thienyl Anion and a Simple Procedure for Introducing a Thiol Group into Thiophene in the Development of a Manufacturing Route to the 5-Lipoxygenase Inhibitor ZD4407,"Process development has been conducted to identify a synthetic route to the 5-lipoxygenase inhibitor ZD4407 that could be used for pilot plant manufacture. Efficient and environmentally acceptable carbon-functionalisation of the 3-position of thiophene using readily available 3-bromothiophene has been achieved using a titanium carbanionic intermediate. An efficient functionalisation of the 5-position with a thiol group has also been realised using dimethyl disulphide, where the side product of the functionalisation reaction is used in situ as the reagent for the subsequent deprotections, thereby considerably reducing the impact on the environment.",10.1021/op960029g,1997-01-01,0.6140690068707533
Tetrahedron,"An efficient asymmetric synthesis of L-α,ω-diaminoalkanoic acids","Efficient asymmetric syntheses of L-2,7-diaminoheptanoic acid and L-2,8-diaminooctanoic acid are described.",10.1016/0040-4039(93)88028-h,1992-12-01,0.6140556302088856
Tetrahedron,Synthesis of enantiopure (R)-2-(4-methoxy-3-(3-methoxypropoxy)-benzyl)-3-methylbutanoic acid—a key intermediate for the preparation of Aliskiren,,10.1016/j.tetlet.2008.07.150,2008-08-06,0.6140450845063711
Journal of Organic Chemistry,"Total Synthesis of the Marine Alkaloids (−)-Lepadins A, B, and C Based on Stereocontrolled Intramolecular Acylnitroso-Diels−Alder Reaction","The first syntheses of (-)-lepadins A and C, as well as a new synthesis of (-)-lepadin B, have been achieved from commercially available (S)-malic acid. The methodology is based on an intramolecular hetero-Diels--Alder reaction of the acylnitroso compound, affording the bicyclic oxazino lactam with trans selectivity, which was converted to the cis-decahydroquinoline via asymmetric enolate hydroxylation followed by intramolecular aldol cyclization. The total syntheses proceed by employing cis-decahydroquinoline bearing the (E)-iodoalkenyl group as the common key intermediate, which underwent a convergent coupling with the (E)-hexenyl unit via a palladium-catalyzed Suzuki cross-coupling reaction for the elaboration of the octadienyl side chain at the C5 position.",10.1021/jo001589n,2001-04-21,0.6140435904611782
European Journal of Organic Chemistry,Chemoenzymatic Asymmetric Total Synthesis of (<i>R</i>)‐Lasiodiplodin Methyl Ether through a Sulfatase‐Based Deracemization Process,"Abstract ( R )‐Lasiodiplodin methyl ether, a precursor of the antileukemic agent lasiodiplodin, was synthesized through a seven‐step linear sequence. Chirality was introduced through a sulfatase‐based deracemization process, in which a functionalized ( rac )‐ sec ‐sulfate ester was enzymatically hydrolyzed with inversion of the stereocenter using an alkyl sulfatase. The remaining sulfate ester enantiomer was hydrolyzed with retention of configuration under acidic conditions, yielding the chiral key building block as the sole product in 93 % ee The total synthesis was completed through Negishi cross‐coupling and ring‐closing metathesis.",10.1002/ejoc.201201296,2012-11-27,0.61403983717031
Tetrahedron,Asymmetric total synthesis of botcinic acid and its derivatives: synthetic revision of the structure of botcinolides,,10.1016/j.tetlet.2008.08.108,2008-09-04,0.6140367303401202
Journal of Organic Chemistry,"A New Short Synthesis of 3-Substituted 5-Amino-1-(chloromethyl)-1,2-dihydro-3<i>H</i>-benzo[<i>e</i>]indoles (Amino-CBIs)","A new short synthesis of 3-substituted 5-amino-1-(chloromethyl)-1,2-dihydro-3H-benzo[e]indoles from Martius Yellow is disclosed. The key steps of the synthesis were three efficient regioselective reactions (iodination, 5-exo-trig aryl radical-alkene cyclization and carboxylation).",10.1021/jo0263115,2002-11-09,0.6140217731381024
Tetrahedron,"A synthetic route to five-, six-, and seven-membered thionolactones",,10.1016/s0040-4039(01)86182-7,1979-01-01,0.6140058607287789
European Journal of Organic Chemistry,Asymmetric Synthesis of a Novel Conformationally Constrained <scp>D</scp>‐Lysine Analogue with a Piperidine Skeleton,"Abstract A practical asymmetric synthesis of enantiomerically pure(2 R ,4 R )‐1‐( tert ‐butoxycarbonyl)‐4‐[2‐(methoxycarbonylamino)ethyl]pipecolic acid starting from easily accessible ( R )‐2‐[( S )‐1,2‐bis(benzyloxy)ethyl]‐1‐[( S )‐1‐phenylethyl]‐4‐piperidone in around 33 % overall yield has been performed. The efficiency of the synthetic strategy developed for the synthesis of this novel conformationally constrained D ‐lysine analogue relies on the high‐yielding Wadsworth–Emmons reaction of a 2‐substituted 4‐piperidone and the diastereoselective reduction of the exocyclic C=C double bond at the 4‐position of the piperidine ring.(© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2008)",10.1002/ejoc.200800069,2008-05-27,0.6139801895736732
Organic Letters,An Efficient Synthesis of Chiral Diamines with Rigid Backbones: Application in Enantioselective Michael Addition of Malonates to Nitroalkenes,"A new and efficient route for synthesis of enantiomerically pure biisoindoline and its isomer based on the diaza-Cope rearrangement reaction with chiral 1,2-bis(2-hydroxylphenyl)-1,2-diaminoethane as starting material has been developed. The newly prepared biisoindoline was employed as a chiral ligand in the Ni(II)-catalyzed enantioselective Michael addition of malonates to conjugated nitroalkenes, and good to excellent enantioselectivities were obtained.",10.1021/ol901776n,2009-09-10,0.6139792306410154
Tetrahedron,Selective N-7 alkylation of 3-methylhypoxanthine; the first synthesis of malonganenone J,,10.1016/j.tetlet.2016.09.078,2016-09-24,0.6139732186511586
Synlett,Novel Applications of the Schöllkopf Chiral Auxiliary: A New and Efficient Enantioselective Synthesis of β-Lactams Possessing a C-4 Quaternary Stereocenter,"A new method for the enantioselective synthesis of substituted β-lactams is described based upon an improved alkylation of substituted Schöllkopf chiral auxiliaries by α-haloacetate esters, employing tert-butyllithium as the deprotonating base, and the efficient conversion of the resulting quaternary 2,5-diketopiperazines to the targeted β-lactams.",10.1055/s-2003-42103,2003-01-01,0.6139632306707326
Journal of Organic Chemistry,"Enantiopure <i>N</i>-Acyldihydropyridones as Synthetic Intermediates:  Asymmetric Syntheses of Indolizidine Alkaloids (−)-205A, (−)-207A, and (−)-235B","Concise asymmetric syntheses of indolizidine alkaloids (-)-205A, (-)-207A, and (-)-235B were accomplished with a high degree of stereocontrol in eleven steps. Addition of 4-(1-butenyl)magnesium bromide to 1-acylpyridinium salt 5, prepared in situ from 4-methoxy-3-(triisopropylsilyl)pyridine and the chloroformate of (+)-trans-2-(alpha-cumyl)cyclohexanol, gave a 91% yield of diastereomerically pure dihydropyridone 6. Oxidative cleavage of 6 and subsequent reduction provided alcohol 7 in 81% yield. Removal of the chiral auxilliary and TIPS group (NaOMe; 10% HCl), N-acylation with BnOCOCCl, and treatment with NCS/Ph(3)P gave chloride 10. Methylation at C-3, copper-mediated conjugate addition of 4-(benzyloxy)butylmagnesium bromide, and vinyl triflate formation provided 13 in a stereoselective fashion. Catalytic reduction of the vinyl triflate moiety, simultaneous cleavage of the benzyl ether and Cbz groups, and cyclization to give amino alcohol 14 was effected via a one-pot reaction. Oxidation of 14 with the Dess-Martin reagent gave a 97% yield of amino aldehyde 4. Synthesis of each of the three title alkaloids was accomplished in one step from 4. The Seyferth-Gilbert reaction provided a 41% yield of (-)-205A. The appropriate Wittig olefination of 4 gave indolizidines (-)-207A and (-)-235B in 70% and 86% yield, respectively.",10.1021/jo971448u,1997-11-01,0.6139597101100178
Journal of Organic Chemistry,Enantioselective Synthesis of Indolizidine Alkaloid <i>trans</i>-209D,"(S)-N-Boc-baikiain, readily accessible from enantiomerically enriched 2,3-epoxy-5-hexen-1-ol 4 (prepared by Sharpless asymmetric epoxidation), was used as the starting material in the synthesis of indolizidine alkaloid trans-209D , which was obtained in 13 steps and 14% yield from 1 (5% from 4).",10.1021/jo801645p,2008-10-08,0.6139351176916158
Journal of the American Chemical Society,Total Synthesis of (−)-Nakadomarin A,The convergent synthesis of the polycyclic alkaloid (-)-nakadomarin A (1) is reported. The synthesis plan identified macrocyclic lactam 4 as one of the important synthons (eight steps). The other synthon (five steps) was bicyclo[6.3.0] lactam 5 containing a single stereocenter that controlled all of the subsequent stereochemistry during the assembly process. A silyl triflate-promoted cascade of 4 and 5 was used to assemble the bulk of the alkaloid skeleton with the exception of the C5-C6 bond. The nakadomarin synthesis was then completed in one additional step.,10.1021/ja404673s,2013-06-10,0.6139338536514859
Tetrahedron,A synthetic approach to actinobolin. Total synthesis of (±)-ramulosin,,10.1016/s0040-4039(01)81333-2,1984-01-01,0.613932732630865
Journal of the American Chemical Society,Total Synthesis of Septedine and 7-Deoxyseptedine,"Septedine ( 2 ) is a hetidine type C 20 -diterpenoid alkaloid bearing an oxygenated heptacyclic scaffold. We have accomplished the first and asymmetric total synthesis of 2 and its 7-deoxy analogue 3 . A functionalized tricyclic intermediate was prepared with excellent enantiopurity by using Carreira polyene cyclization. An unusual anionic Diels–Alder reaction was responsible for the construction of the bicyclo[2.2.2]octane. The α-methyl ketone was furnished by iridium-catalyzed allylic alcohol isomerization. Sanford Csp 3 –H oxidation was exploited to install the secondary hydroxy group of 2 . The oxazolidinopiperidine was assembled by selective reductive amination and spontaneous N, O -ketalization at a final stage.",10.1021/jacs.8b03712,2018-06-06,0.6139222450283637
Journal of the American Chemical Society,Total Synthesis of (+)-Trienomycins A and F via C–C Bond-Forming Hydrogenation and Transfer Hydrogenation,"The triene-containing C17-benzene ansamycins trienomycins A and F were prepared in 16 steps (longest linear sequence, LLS) and 28 total steps. The C11-C13 stereotriad was generated via enantioselective Ru-catalyzed alcohol CH syn crotylation followed by chelation-controlled carbonyl dienylation. Enantioselective Rh-catalyzed acetylene-aldehyde reductive coupling mediated by gaseous H2 was used to form a diene that ultimately was subjected to diene-diene ring closing metathesis to form the macrocycle. The present approach is 14 steps shorter (LLS) than the prior syntheses of trienomycins A and F, and 8 steps shorter than any prior synthesis of a triene-containing C17-benzene ansamycin.",10.1021/ja4061273,2013-07-17,0.6139195393184099
Journal of the American Chemical Society,Concise Synthesis of Fostriecin and Analogs through Late-Stage Chemoenzymatic Installation of Their Key Pharmacophores,"As one of the most potent and selective protein phosphatase inhibitors, fostriecin shows a broad range of anticancer activities. In light of this property, a phase I clinical trial was conducted on fostriecin but was soon halted due to issues with compound stability and purity. Numerous efforts in the past two decades have yielded 17 successful syntheses that proceed in 17–34 steps. Herein, we develop a modular chemoenzymatic approach that provides fostriecin and its analogs in a collective manner in 9 steps (longest linear sequence) from readily available ( R )-1,2,4-butanetriol. The synthesis features a convergent assembly of three key fragments and a late-stage chemoenzymatic derivatization of an advanced intermediate that (i) installs two of the key pharmacophores and (ii) allows ready diversification of the hydrophobic tail. A key feature in this derivatization is the optimization of an enzymatic C–H oxidation step through the concurrent use of rational enzyme engineering and small molecule additives for activity improvement. Cumulatively, our strategy capitalizes on the exquisite chemoselectivity of enzymatic transformations while ensuring synthetic modularity and versatility for analog generation. This work will facilitate future investigations into the biological activities and medicinal chemistry of the natural product family.",10.1021/jacs.5c05269,2025-07-09,0.6139167195929411
Tetrahedron,A new synthetic approach for 4(S)-hydroxycyclopent-2-enone: a precursor to prostanoid synthesis,,10.1016/j.tetlet.2005.07.035,2005-07-28,0.6139037909406881
Journal of Organic Chemistry,Microwave-Assisted Synthesis of Substituted Tetrahydropyrans Catalyzed by ZrCl<sub>4</sub> and Its Application in the Asymmetric Synthesis of <i>exo</i>- and <i>endo</i>-brevicomin,"The ZrCl4-catalyzed deprotection of 1,3-dioxane/dioxalane and the simultaneous formation of 6-methoxy-substituted tetrahydropyrans proceeded under microwave irradiation in good yield. This synthetic methodology was used for the asymmetric synthesis of (+)-exo- and (+)-endo-brevicomin in 55% overall yield over 4 steps.",10.1021/jo901019u,2009-07-02,0.6138916532333943
Organic Letters,Iridium-Catalyzed Asymmetric Hydrogenation of γ- and δ-Ketoacids for Enantioselective Synthesis of γ- and δ-Lactones,"A highly efficient asymmetric hydrogenation of γ- and δ-ketoacids was developed by using a chiral spiro iridium catalyst ( S )- 1a, affording the optically active γ- and δ-hydroxy acids/lactones in high yields with excellent enantioselectivities (up to >99% ee) and turnover numbers (TON up to 100000). This protocol provides an efficient and practical method for enantioselective synthesis of Ezetimibe.",10.1021/acs.orglett.9b04253,2020-01-21,0.613884410804986
Synthesis,Facile Enantiospecific Synthesis of Dihydroconduritols E and F,"An enantiospecific synthesis of cyclohexane-1,2,3,4-tetrols was accomplished from l-(+)-tartaric acid. Pivotal steps in the synthetic sequence include zinc-mediated Boord-type fragmentation of an acetonide, ring-closing metathesis (RCM), and osmium-mediated dihydroxylation.",10.1055/s-2008-1067261,2008-09-05,0.6138809060500895
Journal of Organic Chemistry,"An Expeditious Route to Novel 1,4,2-Benzodiazaphosphepin-5-one 2-Oxide Analogues","A short and efficient synthesis of the novel 1,4,2-benzodiazaphosphepin-5-one 2-oxide ring system, a phosphonamidate isostere of the 1,4-benzodiazepine-2,5-dione system, has been carried out in good overall yield. The key step is the base-induced cyclization of (2-aminobenzamido)methylphosphonates 6a-c to the 1,4,2-benzodiazaphosphepin-5-one 2-oxides 7a-c. Alkylation of 7b with methyl iodide gives the expected N-methyl analogue 9. When a tandem one-pot cyclization/alkylation is carried out from 6b in the presence of excess base, the sole isolable product obtained is the phosphonate 13, presumably via ethanolysis of a transiently formed 9. Carrying out the tandem cyclization/alkylation in the absence of excess base, however, affords only 9. Thionation of 7 with Lawesson's reagent occurs at either the phosphonamidate oxygen (P-2) or the amide carbonyl (C-5) depending on the steric constraint of the N-4 substituent.",10.1021/jo9908400,1999-10-01,0.6138793883685637
European Journal of Organic Chemistry,Expedient Synthesis of Thioether‐Functionalized Hydrotris(indazolyl)borate as an Anchoring Platform for Rotary Molecular Machines,"Major improvements in the synthesis of surface‐mounted rotary molecular machines based on ruthenium(II) complexes are reported. The development of a one‐pot indium(III)‐mediated “ N ‐deprotection/ester reductive sulfidation” sequence allowed step economy, reproducibility and high efficiency in the synthesis of the thioether‐functionalized tripodal ligand. Switching to the thallium salt of hydrotris(indazolyl)borate and to microwave heating further optimized the preparation of the common intermediate in the modular synthesis of symmetric and dissymmetric molecular motors and gears. The penta(4‐bromophenyl)cyclopentadienyl ruthenium(II) key precursor is now reproducibly synthesized in 5 steps and 31 % overall yield on the longest linear sequence. Subsequent fivefold Suzuki–Miyaura coupling with ferroceneboronic acid led to a new C 5 ‐symmetric pentaferrocenyl molecular motor.",10.1002/ejoc.201800990,2018-06-28,0.6138787272607635
Organic Process Research & Development,Efficient Manufacturing Process for the Selective Estrogen Receptor Degrader GDC-9545 (Giredestrant) via a Crystallization-Driven Diastereoselective Pictet–Spengler Condensation,"GDC-9545 is a selective estrogen receptor degrader that is being developed as a treatment for ER+/HER2– breast cancer. A robust, convergent manufacturing process for GDC-9545 was developed. The process features a Wenker aziridine synthesis to produce the key starting material tryptamine 11, a highly efficient C–N coupling between aminoazetidine 9 and 2,6-difluoro-4-bromobenzaldehyde diethyl acetal ( 33 ) to construct key intermediate 10, and a crystallization-driven diastereoselective Pictet–Spengler reaction to furnish the active pharmaceutical ingredient GDC-9545·tartrate.",10.1021/acs.oprd.1c00263,2021-11-09,0.6138728367908989
Angewandte Chemie International Edition,Total Synthesis of Anti‐Cancer Meroterpenoids Dysideanone B and Dysiherbol A and Structural Reassignment of Dysiherbol A,The first total synthesis of marine anti-cancer meroterpenoids dysideanone B and dysiherbol A have been accomplished in a divergent way. The synthetic route features: 1) a site and stereoselective α-position alkylation of a Wieland-Miescher ketone derivative with a bulky benzyl bromide to join the terpene and aromatic moieties together and set the stage for subsequent cyclization reactions; 2) an intramolecular radical cyclization to construct the 6/6/6/6-tetracycle of dysideanone B and an intramolecular Heck reaction to forge the 6/6/5/6-fused core structure of dysiherbol A. A late-stage introduction of the ethoxy group in dysideanone B reveals that this group might come from the solvent ethanol. The structure of dysiherbol A has been revised based on our chemical total synthesis.,10.1002/anie.202100541,2021-04-13,0.6138580910155316
Journal of Organic Chemistry,Asymmetric Total Synthesis of the Indole Diterpene Alkaloid Paspaline,"An enantioselective synthesis of the indole diterpenoid natural product paspaline is disclosed. Critical to this approach was the implementation of stereoselective desymmetrization reactions to assemble key stereocenters of the molecule. The design and execution of these tactics are described in detail, and a thorough analysis of observed outcomes is presented, ultimately providing the title compound in high stereopurity. This synthesis provides a novel template for preparing key stereocenters in this family of molecules, and the reactions developed en route to paspaline present a series of new synthetic disconnections in preparing steroidal natural products.",10.1021/acs.joc.5b01844,2015-09-23,0.6138492716061517
Tetrahedron,"2-Amino-6-(1,2,4-triazol-4-yl)-purine: a useful intermediate in the synthesis of 9-alkylguanines",,10.1016/s0040-4039(00)01236-3,2000-09-01,0.613842357012291
Journal of Organic Chemistry,Total Synthesis of (+)-Mupirocin H from <scp>d</scp>-Glucose,"Enantioselective total synthesis of mupirocin H is accomplished starting from D-glucose featuring strategic application of D-glucose derived chirality, diastereoselective Still-Barrish hydroboration, and further elaboration of carbon chain to furnish a phenyltetrazolyl sulfone intermediate, which on coupling with (2S,3S)-2-methyl-3-(triisopropylsilyloxy)butanal under Julia-Kocienski olefination conditions gave an advanced E-olefinic intermediate selectively. The E-olefin was transformed to the 4-hydroxynitrile, a prefinal substrate, which on acid-catalyzed oxidative lactonization furnished the target molecule mupirocin H in 19 steps from known compound 6 (longest linear sequence) with an overall yield of 4.96%.",10.1021/jo200396q,2011-06-27,0.6138352764787937
Journal of the American Chemical Society,A Thio-Diels−Alder Route to the Azocine Ring System. Total Synthesis of (±)-Otonecine,"A sulfur-based strategy for synthesis of otonecine is described. Key steps include the thio-Diels−Alder trapping of thioketone 8 by the Danishefsky diene, followed by conversion into the enone 27 and internal Michael addition to afford bicyclic thioaminal 28 . Selective C−S bond cleavage was achieved after conversion to alcohol 36 or its derivatives 38, resulting in the azocine ring system. The successful route proceeded from 40b via 49a and sulfoxide elimination to the alkene 50a . The final conversions to otonecine were accomplished via low-temperature osmylation of 56, a crucial OsO 4 -mediated oxidation of diol 58 to ketol 60/61, and Burgess elimination to 68/69 . Several of the intermediates in late stages of the synthesis exist largely in the bicyclic valence bond tautomer form that is characteristic of the otonecine ring system.",10.1021/ja973464e,1998-04-01,0.6138236264941547
Tetrahedron,"Efficient, two-step synthesis of N-substituted nortropinone derivatives",,10.1016/j.tetlet.2007.05.110,2007-05-25,0.6138217272829952
Journal of Organic Chemistry,"Enantioselective Synthesis of Primary 1-(Aryl)alkylamines by Nucleophilic 1,2-Addition of Organolithium Reagents to Hydroxyoxime Ethers and Application to Asymmetric Synthesis of G-Protein-Coupled Receptor Ligands","(E)-Arylaldehyde oxime ethers bearing a (1S)-2-hydroxy-1-phenylethyl or (2R)-1-hydroxy-2-phenylethyl group as a chiral auxiliary, both derived from a single precursor, methyl (R)-mandelate, underwent nucleophilic addition with organolithium reagents via six-membered chelates to give the diastereomerically enriched (R)- and (S)-adducts, respectively, which, after chiral auxiliary removal by reductive N-O bond cleavage, led to the corresponding (R)- and (S)-1-(aryl)ethylamines. This organolithium addition protocol using methyllithium was applied in an enantiodivergent fashion to the preparation of both enantiomers of 1-(2-hydroxyphenyl)ethylamine, which has been previously used as an efficient chiral auxiliary for the synthesis of natural products in this laboratory. The synthetic utility of this methodology involving diastereoselective methyl addition was demonstrated by further application to the asymmetric synthesis of a new type of calcium receptor agonist (calcimimetics), (R)-(+)-NPS R-568 and its thio analogue. Furthermore, diastereoselective vinylation was accomplished by application of the hydroxy oxime ether-based protocol using vinyllithium, which allowed the development of the enantioselective synthesis of the NK-1 receptor antagonists, (+)-CP-99,994 and (+)-CP-122,721.",10.1021/jo049517+,2004-07-17,0.613811820184114
Green Chemistry,A chiral biselectrophile for efficient asymmetric synthesis in water,"The development of an efficient asymmetric dihydroxylation of 1,6-dibromodiene afforded a chiral biselectrophilic diol that displayed highly useful reactivity in water, as demonstrated by a three-step, two-pot asymmetric synthesis of a highly functionalized tetrahydrofuran.",10.1039/b415300f,2005-01-01,0.6138090262360271
Journal of Organic Chemistry,Synthetic Approaches to Racemic Porantheridine and 8-Epihalosaline via a Nitroso Diels−Alder Cycloaddition/Ring-Rearrangement Metathesis Sequence,"The application of a sequence involving a nitroso Diels-Alder cycloaddition and a ring-rearrangement metathesis to the total synthesis of (+/-)-8-epihalosaline and the formal synthesis of (+/-)-porantheridine is described. The formation of the 2,6-trans-disubstituted piperidine backbone of porantheridine has been accomplished by addition of a Grignard reagent onto an N-benzylpiperidone followed by a highly diastereoselective reduction of the imminium intermediate in one pot.",10.1021/jo100768d,2010-05-26,0.6138078057709317
Organic Process Research & Development,Development of a Practical and Efficient Synthesis of Chloromethyl 2-Ethoxy-2-methylpropanoate,"An efficient synthesis of chloromethyl 2-ethoxy-2-methylpropanoate from 2-bromoisobutyric acid is reported. Four developments were key to this route: (i) a mild, base-mediated ethanolysis of a tertiary alkyl bromide, (ii) a sodium bisulfite purge of 2-methylacrylic acid, (iii) preparation of a thiomethyl ester via a formal Pummerer process with DMSO, and (iv) improved conversion of a thiomethyl ester to a chloromethyl ester through suppression of a competing chlorination pathway.",10.1021/op1002038,2010-10-27,0.6137988155060804
Synlett,Total Synthesis of the Naturally Occurring Endothelin Converting Enzyme (ECE) Inhibitor WS 75624 A,"The ECE inhibitor WS 75624 A (1a) was synthesized following a convergent strategy. 2,4-Dibromothiazole (2) served as the central building block, which underwent consecutive cross-coupling reactions. In the first C-C bond formation step, it was substituted at carbon atom C-2 by a C7-alkylzinc chloride derived from iodide 8 (85% yield). In the second step, the intermediate 4-bromothiazole 9 was converted to the corresponding stannane 10 which was coupled at carbon atom C-4 to the 2-iodopyridine 6 (75% yield).",10.1055/s-2002-35568,2002-01-01,0.6137961644101019
Journal of Organic Chemistry,Synthetic Studies toward Ecteinascidin 743,"An efficient synthesis of a fully functionalized tetracycle (A-B-C-H) 7 containing a 1,4-bridged 10-membered lactone was developed. Phenolic aldol condensation between 2-methylsesamol (15) and Garner's aldehyde provided the protected amino diol 16, which was converted to free amine 11 in excellent yield. A Pictet-Spengler reaction between 11 and ethyl glyoxylate under carefully controlled conditions (LiCl, toluene, 1,1,1,3,3,3-hexafluoro-2-propanol, room temperature) provided the acid-sensitive tetrahydroisoquinoline (18) in high yield, which was converted to the amino alcohol 9. Enantioselective alkylation of a glycine template in the presence of a catalytic amount of chiral cinchonidium salt was the key step for the access of enantiomerically pure amino aldehyde 10. Union of the two fragments 9 and 10 via oxazolidine intermediate afforded amino nitrile 39, which upon esterification of the primary alcohol with (R)-N-(S-4,4',4' '-trimethoxyltrityl) Cys (42) afforded 43. Cyclization of 43 (1% trifluoroacetic acid in trifluoroethanol) provided compound 44 by a domino process involving (a) unmasking of the S-trimethoxytrityl group, (b) fragmentation of dioxane assisted by an electron-rich aromatic ring, and (c) formation of a 1,4-bridged 10-membered lactone via formation of a sulfide linkage. Treatment of 7, obtained in two steps from 44b, under acidic conditions (0.5% methyl sulfonic acid in acetonitrile) afforded the pentacyclic compound 51 via fragmentation of the 10-membered cyclic sulfide followed by an intramolecular Pictet-Spengler reaction.",10.1021/jo050408k,2005-04-28,0.6137903188997017
Organic Letters,Oxidative Coupling as a Biomimetic Approach to the Synthesis of Scytonemin,"The first total synthesis of the dimeric alkaloid pigment scytonemin is described. The key transformations in its synthesis from 3-indole acetic acid are a Heck carbocyclization and a Suzuki-Miyaura cross-coupling, orchestrated in a stereospecific tandem fashion, followed by a biosynthetically inspired oxidative dimerization. The tandem sequence generates a tetracyclic (E)-3-(arylidene)-3,4-dihydrocyclopenta[b]indol-2(1H)-one that is subsequently dimerized into the unique homodimeric core structure of scytonemin.",10.1021/ol201812n,2011-07-25,0.6137887591278772
Tetrahedron,Efficient asymmetric synthesis of 3-substituted β-sultams,,10.1016/s0040-4039(02)00980-2,2002-07-01,0.6137822917098238
Journal of Organic Chemistry,A Synthetic Route to Highly Substituted 1-Aminonaphthalenes from Readily Available Benzaldehydes,"We report an efficient route for the synthesis of highly substituted 1-aminonaphthalenes from benzaldehydes. The method employs a stereoselective Still–Gennari modification of the Horner–Wadsworth–Emmons olefination to afford ( E )-benzylidenesuccinonitrile precursors, which undergo Bronsted acid mediated benzannulation to afford 1-aminonaphthalene derivatives in 35–95% yield. The abundance of commercially available benzaldehydes, coupled with the simplicity of our method, enables many previously unexplored naphthalene substitution patterns to become readily accessible.",10.1021/acs.joc.3c02324,2024-01-03,0.6137722863109693
Tetrahedron,Novel diastereoselective synthesis of (E)- and (Z)-allylsilanes via organoboranes,,10.1016/j.tetlet.2007.04.052,2007-04-20,0.6137720908738822
Organic Process Research & Development,Exploratory Process Development of a High-Temperature Thermal (3 + 2) Cycloaddition in Continuous Flow for the Synthesis of Seltorexant,"Seltorexant ( 1 ) is currently under clinical development as a selective orexin-2 antagonist for the treatment of major depressive disorder with insomnia symptoms. During the investigation of an improved synthesis route, a key (3 + 2) cycloaddition reaction was found to occur only at very high temperatures (>250 °C). An exploratory process development of such a challenging high-temperature cycloaddition was demonstrated in a continuous flow process. Together with the development of other steps, a proof of concept to the improved synthesis route to seltorexant was established.",10.1021/acs.oprd.3c00113,2023-07-07,0.6137579321924499
Tetrahedron,"A new route to 1,1-difluoro olefins: Application to the synthesis of 2′-deoxy-2′-difluoromethylene nucleosides.",,10.1016/s0040-4039(00)79824-8,1992-05-01,0.6137565051581352
Journal of the American Chemical Society,A Concise Total Synthesis of Glycinoeclepin A,"Here we report a concise and modular synthesis of the complex triterpenoid glycinoeclepin A, a picomolar hatching stimulus for the notorious pest soybean cyst nematode. The synthesis features the strategic use of a polyfunctional platform intermediate bearing an aldehyde, a vinyl triflate, and an exo -cyclic alkene─three functional groups with orthogonal reactivity. From here, a programmable Cr-mediated diastereoselective homoallenylation of aldehyde, followed by a Pd-catalyzed intramolecular oxygenative cyclization, efficiently forged the densely functionalized 5,6-fused core system. The oxa -bicyclic appendage was installed via an allyl phosphonate enabled coupling. The remaining alkene was selectively homologated via a hydroboration, Wittig reaction. Final oxidations completed the total synthesis of glycinoeclepin A. This concise route not only provides access to glycinoeclepin A and analogs for potential biological studies but also establishes a general platform for synthesizing architecturally complex polycyclic natural products.",10.1021/jacs.5c07696,2025-06-25,0.6137491889009589
Journal of Organic Chemistry,A Carbohydrate-Based Approach for the Total Synthesis of Aculeatin D and 6-<i>epi</i>-Aculeatin D,"A concise approach for the total synthesis of aculeatin D and 6-epi-aculeatin D employing differentially protected anti, anti-1,3,5-triol alkyne prepared from alpha-D-glucoheptonic-gamma-lactone derivative is documented. Phenol protecting group manipulation for selective O-debenzylation during the hydrogenation of the diyne intermediate and one-pot phenolic oxidation with concomitant spiroketalization highlight the accomplished total synthesis.",10.1021/jo800026n,2008-04-15,0.6137472536389063
Tetrahedron,"Synthesis of an unnatural product - 4,4' biaryl formation as a macrocyclisation step",,10.1016/0040-4039(94)88001-8,1994-02-01,0.6137447755025186
Tetrahedron,"Synthesis of an unnatural product -- 4,4′ biaryl formation as a macrocyclisation step",,10.1016/0040-4039(94)85086-0,1994-01-01,0.6137447755025186
Organic Letters,Total Synthesis of (±)-Martinellic Acid,"A 14-step synthesis of martinellic acid (1) that proceeds in 3% overall yield has been completed using the reaction of aniline 11 with Meldrum's acid-activated vinylcyclopropane 4 to give vinyl pyrrolidinone 12, condensation of aldehyde 13 with N-benzylglycine to form an azomethine ylide that cyclizes to give 14, selective reduction of 14 to amino alcohol 16 with LiBH(4) and MeOH, and guanidine formation by reaction of a cyanamide with 3-methyl-2-buten-1-amine in hexafluoro-2-propanol at 120 degrees C as key steps. [structure: see text]",10.1021/ol016884o,2001-11-29,0.6137412060423478
Organic Letters,Synthetic Efforts toward Lannotinidine G Based on an Aziridinium-Mediated Ring Contraction and Dienyne Metathesis,"Lannotinidine G is a unique Lycopodium alkaloid that features a tricyclic [6/6/6] core with 3 contiguous stereocenters and a 1,3-diene moiety in addition to a 7-membered lactone. Herein, we disclose our efforts toward the synthesis of this natural product, which achieved the construction of the aza-tricyclic core with the correct configuration at its three stereocenters. Key features of our strategy include a highly diastereoselective Fráter-Seebach alkylation and Corey-Chaykovsky type epoxide formation, an unusual aziridinium-mediated ring contraction for the formation of the piperidine moiety, and a regioselective dienyne metathesis.",10.1021/acs.orglett.4c00791,2024-04-02,0.6137408276285201
Angewandte Chemie International Edition,Total Synthesis of (−)‐Quinocarcin by Gold(I)‐Catalyzed Regioselective Hydroamination,"In control: The novel and enantioselective total synthesis of (-)-quinocarcin includes the highly stereoselective preparation of the 2,5-cis-pyrrolidine by intramolecular amination, a selective substrate-controlled 6-endo-dig intramolecular alkyne hydroamination with a cationic Au(I) catalyst, and Lewis-acid-mediated ring-opening/halogenation sequence.",10.1002/anie.201205106,2012-08-13,0.6137392366311237
Journal of Organic Chemistry,Synthesis of Carbocycles via Intramolecular Conjugate Additions:  Total Syntheses of Axane Sesquiterpenoids,"Syntheses of (+/-)-axamide-1 (2) and (+/-)-axisonitrile-1 (1) are described. The syntheses require 12 steps and 13 steps, respectively, from vinylogous ester 8 and feature the diastereoselective cyclization of unsaturated ester 7 to perhydroindan 5. Some interesting reactions of the organometallic derived from [(trimethylsilyl)methyl]magnesium chloride and cerium trichloride are also described.",10.1021/jo951532e,1996-01-01,0.613730244165657
Synthesis,"4-<i>O</i>-Benzyl-2,3-<i>O</i>-isopropylidene-D-erythrose and -D-threose from 2,3-<i>O</i>-Isopropylidene-D-glyceraldehyde via Thiazole Intermediates. Synthesis of 2-Deoxykanosamine","All articles of this category The adduct derived from 2,3- O -isopropylidene-D-glyceraldehyde and 2-(trimethylsilyl)thiazole is readily converted into the title D-erythrose (50% overal yield) by selective protection of the hydroxy groups and cleavage of the thiazole ring; the D-threose derivative is obtained from the former by base-catalyzed epimerization at C-2. Wittig olefination of the D-erythrose derivative followed by Michael addition of benzylamine and aldehyde liberation from the thiazole ring leads to the amino sugar 2-deoxykanosamine (methyl 6- O -benzyl-3-benzylamino-2,3-dideoxy-α -D-arabinopyranoside) in 50% overall yield.",10.1055/s-1992-34166,1992-01-01,0.613728406271413
Organic Letters,An approach to (±)-Lingzhiol,"(±)-Lingzhiol has been synthesized from commercially available 5,8-dimethoxytetralone in seven steps with an overall yield of 10.3% via an unprecedented acid-catalyzed semipinacol-type rearrangement. In addition, a novel strategy for the construction of the tetracyclic 5/5/6/6 core structure of lingzhiol has been developed via a tandem rearrangement/reduction/lactonization reaction.",10.1021/acs.orglett.6b00542,2016-04-04,0.6137259159567273
Organic Letters,Enantioselective Total Synthesis of (+)-Lysergol: A Formal <i>anti</i>-Carbopalladation/Heck Cascade as the Key Step,"The enantioselective synthesis of (+)-lysergol was completed in 12 steps and an overall yield of 13% starting from a known literature precursor. The key step relies on a domino reaction containing a formal anti-carbopalladation, which is terminated by a β-silyl-directed Heck reaction. During this transformation, the two six-membered rings of the ergot scaffold are formed in a completely stereospecific manner.",10.1021/acs.orglett.7b00675,2017-03-30,0.613718347871438
European Journal of Organic Chemistry,"A Concise Synthesis of <i>R</i>‐(–)‐Cicutoxin, a Natural 17‐Carbon Polyenyne","Abstract A concise synthesis of the natural polyenyne R ‐(–)‐cicutoxin ( 1 ) is described. After several trials, the successful synthesis commenced with three key fragments, R ‐(–)‐1‐hexyn‐3‐ol ( 8 ), 1,4‐diiodo‐1,3‐butadiene ( 9 ), and THP‐protected 4,6‐heptadiyn‐1‐ol ( 6 ). Sonogashira coupling of compound 9 with acetylenes 6 and 8 gave the 17‐carbon frame, which upon regioselective reduction of a triple bond with Red‐Al and removal of the THP protecting group afforded the natural product in four linear steps. The triply convergent synthesis gave R ‐(–)‐cicutoxin in 18 % overall yield. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2009)",10.1002/ejoc.200801172,2009-01-28,0.6137150324026808
Tetrahedron,"A new approach to the synthesis of cross-conjugated cyclopentenone prostaglandins. Synthesis of (±)-15-deoxy-Δ12,14-prostaglandin J2 methyl ester",,10.1016/j.tetlet.2014.08.096,2014-08-29,0.6137099291454973
Synthesis,"A Concise Route for the Synthesis of Biologically Interesting Pyranocoumarins - Seselin, (±)-<i>cis</i>-Khellactone, (±)-Quianhucoumarin D, and the (±)-5-Deoxyprotobruceol-I Regioisomer","An efficient synthesis of pyranocoumarins is achieved starting from 2H-pyrans. This process provides naturally occurring seselin, cis-khellactone, quianhucoumarin D, and the 5-deoxyprotobruceol-I regioisomer.",10.1055/s-2006-926329,2006-01-01,0.6137063914399442
Journal of Organic Chemistry,"Stereoselective Synthesis of (<i>E</i>)-β-Tributylstannyl-α,β-unsaturated Ketones:  Construction of a Key Intermediate for the Total Synthesis of Zoanthamine","(E)-beta-Trialkylstannyl-alpha,beta-unsaturated ketones are readily available from secondary propargylic alcohols via a two-step sequence involving highly regio- and stereoselective Pd(0)-catalyzed hydrostannation followed by mild oxidation (TPAP). The methodology has been applied to the synthesis of enantiomerically pure enone 12 which is a key intermediate for the total synthesis of zoanthamine, a structurally complex marine natural product.",10.1021/jo025902s,2002-08-03,0.6137045748927905
Tetrahedron,"Novel synthesis of CP-734432, an EP4 agonist, using Sharpless asymmetric dihydroxylation",,10.1016/j.tetlet.2009.12.092,2009-12-24,0.6136960335644905
Journal of Organic Chemistry,Enantioselective Synthesis of Tetrahydroquinolines from 2-Aminochalcones via a Consecutive One-Pot Reaction Catalyzed by Chiral Phosphoric Acid,"A new asymmetric protocol for the synthesis of chiral tetrahydroquinolines from 2-aminochalcones via a two-step one-pot consecutive process (cyclization/asymmetric reduction) has been developed using chiral phosphoric acid as the sole catalyst. 2-Aminochalcones were converted into the corresponding quinolines through chiral phosphoric acid-catalyzed dehydrative cyclization, and the resultant quinolines were subsequently reduced to the chiral tetrahydroquinolines via chiral phosphoric acid-catalyzed asymmetric reduction with Hantzsch ester. Various 2-aminochalcones could be applicable to this protocol, and the desired tetrahydroquinolines were obtained in excellent yields and with excellent enantioselectivities. Furthermore, the utility of this protocol has been successfully demonstrated in the highly efficient synthesis of estrogen receptor modulator.",10.1021/acs.joc.8b01709,2018-09-26,0.6136797594966634
Journal of the American Chemical Society,Total Synthesis of Herquline B and C,"The total syntheses of (-)-herquline B (2) and a heretofore-unrecognized congener, (+)-herquline C (3), are described. The syntheses require 14 and 13 steps, respectively, and feature a key oxazoline reduction that sets the stage for piperazine construction.",10.1021/jacs.8b10212,2018-12-18,0.6136654692513742
European Journal of Organic Chemistry,Total Synthesis of the Putative Structure of Deoxypumiliotoxin 193H by an Ireland–Claisen Rearrangement,Abstract A stereoselective total synthesis of one diastereomer of 8‐deoxypumiliotoxin 193H is described. The concise total synthesis features the use of readily available natural amino acids as the starting materials and the Ireland–Claisen rearrangement as the key stereochemistry controlling step.,10.1002/ejoc.201500063,2015-04-07,0.6136570851093144
Tetrahedron,"A novel stereospecific synthesis of (±)-leukotriene A4(LTA4), methyl ester",,10.1016/s0040-4039(00)88375-6,1982-01-01,0.6136513333379162
Organic Process Research & Development,Development of a Practical Manufacturing Process to Relebactam via Thorough Understanding of the Origin and Control of Oligomeric Impurities,"The development of a robust manufacturing process to relebactam, a potent β-lactamase inhibitor, is described. The origin and control strategy of oligomer impurities formed during hydrogenolysis of benzyl urea intermediate 9 and deprotection of Boc-sulfate intermediate 11 have been thoroughly studied and developed. The optimal manufacturing process has been successfully implemented for commercialization, preparing relebactam ( 1 ) in >99% purity with a non-detectable level of oligomers.",10.1021/acs.oprd.1c00149,2021-09-13,0.6136477533894252
Tetrahedron,A new stereoselective synthesis of a γ-azetidinylgb-hydroxy-α-amino acid moiety of mugineic acid — a formal synthesis of mugineic acid,,10.1016/s0040-4039(00)97800-6,1990-01-01,0.6136459019099453
Tetrahedron,An efficient one pot synthesis of 2-amino quinazolin-4(3 H )-one derivative via MCR strategy,,10.1016/j.tetlet.2015.08.040,2015-08-21,0.6136453348878944
Journal of Organic Chemistry,An Inexpensive and Scalable Synthesis of Shld,"A synthesis of the important FKBP ligand Shld is reported. The synthesis avoids stoichiometric use of expensive and chiral reagents, maintains enantioselectivity and provides a high overall yield (39%). The main features in the method are enantioselective alkylation for preparation of the phenyl acetic acid moiety (building block A), catalytic enantioselective reduction for obtaining the chiral diaryl-1-propanol (building block C), and direct acylation of S-pipecolic tartrate rather than use of expensive Fmoc-pipecolic acid. The assembly of the building blocks A-C is reversed in comparison to previous synthesis, which also eliminates the need for protective groups.",10.1021/acs.joc.8b00698,2018-05-11,0.6136309015781677
Journal of the American Chemical Society,Streamlined Strategy for Scalable and Enantioselective Total Syntheses of the Eburnane Alkaloids,"A general, concise, and efficient strategy for the enantioselective synthesis of the eburnane alkaloid family of natural products is disclosed. Specifically, 13 members of the natural product family were prepared from commercially available and inexpensive starting materials. The brevity and modularity of the route are largely on account of a two-phase synthesis logic and a key catalytic enantioconvergent cross-coupling to establish the C20 stereogenic center. The strategies described here are expected to facilitate in-depth biological studies and provide access to new anticancer eburnane analogues.",10.1021/jacs.3c07019,2023-08-30,0.613627144918752
Organic Letters,Stereoselective Synthesis of 3-Aryloctahydroindoles and Application in a Formal Synthesis of (−)-Pancracine,A stereoselective synthesis of 3-aryloctahydroindoles from enantiomerically enriched gamma-nitroketones has been developed. Reduction of imines derived form the nitroketones provides the trans-fused octhaydroindole motif selectively. The cis-octahydroindole skeleton is accessible by an invertive cyclization strategy involving a diastereomerically pure nitromesylate intermediate. This approach was employed in the synthesis of an advanced intermediate to (-)-pancracine. The gamma-nitroketone starting materials are readily available via an organocatalytic Michael reaction.,10.1021/ol902761a,2010-01-07,0.6136222871237819
Tetrahedron,Carbanion addition to acetylenes : An efficient stereoselective route to α-methylene-γ-lactams,,10.1016/s0040-4039(00)79668-7,1991-03-01,0.6136032418885407
Journal of the American Chemical Society,"Asymmetric Synthesis of Salvinorin A, A Potent κ Opioid Receptor Agonist",The stereoselective synthesis of salvinorin A is described. A macrocyclic bis-Michael reaction cascade provides the requisite tricyclic skeleton as a single diastereomer.,10.1021/ja073590a,2007-06-30,0.6135971133887577
Journal of the American Chemical Society,Enantioselective Total Synthesis of (+)-Dibromophakellstatin,"The first enantioselective total synthesis of (+)-phakellstatin and (+)-dibromophakellstatin was achieved. Key steps in the synthesis were a desymmetrization of the diketopiperazine (S,S)-cyclo (Pro, Pro) via a diastereoselective acylation, an intramolecular Mitsunobu reaction to introduce the C6 aminal, and a tandem Hofmann rearrangement/cyclization to simultaneously introduce the C10 quaternary aminal center and deliver the cyclic urea. The synthesis also demonstrates the unusual stability of pyrrolo aminals. Importantly, this strategy has the potential for producing phakellstatin derivatives, derived from (R,R)-cyclo (Pro, Pro), necessary for biological studies. A similar annulation protocol is also expected to be applicable to the synthesis of palau'amine.",10.1021/ja034575i,2003-05-01,0.6135915189418202
Organic Letters,One-Step Synthesis of Heteroaromatic-Fused Pyrrolidines via Cyclopropane Ring-Opening Reaction:  Application to the PKCβ Inhibitor JTT-010,"A ring-opening reaction of cyclopropanes with five-membered heteroaromatics having a leaving group at C(2) was found to provide heteroaromatic-fused pyrrolidines in one step. This reaction was successfully applied to the synthesis of the protein kinase C-beta inhibitor JTT-010, which possesses a dihydropyrrolo[1,2-a]indole core.",10.1021/ol071336h,2007-07-26,0.6135830469847339
Synlett,A Concise and Convergent Synthesis of Luotonin B and E,A concise and highly convergent practical synthesis of topoisomerase 1 inhibitor luotonin B was developed in a one-pot process in excellent yields. The C and D rings of luotonin B was constructed by cascade cyclizations of 2-cyanoquinoline-3-aldehyde or 2-cyanoquinoline-3-hemiacetal with methylanthranilate under acidic conditions. The luotonin B was then converted into luotonin E by an acid-catalyzed etherification reaction.,10.1055/s-0030-1259098,2010-12-10,0.6135820840287601
Synlett,The Synthesis of 6-Deazaformycin A,"The synthesis of the new C-nucleoside 6-deazaformycin A was achieved through the condensation of a suitably substituted lithiated 2-picoline with 2,3,5-tri-O-benzyl-d-ribonolactone, borohydride reduction of the resulting hemiacetals, followed by intramolecular Mitsunobu cyclization of the carbinols, manipulation of the protecting groups, and subsequent ring closure to result in the formation of 7-amino-3-(β-d-ribofuranosyl)pyrazolo[4,3-b]pyridine.",10.1055/s-0029-1218002,2009-10-02,0.613559908748988
Journal of Organic Chemistry,Studies toward the Synthesis of Lepadiformine A,"Herein is described an original approach to access a tricyclic framework of the lepadiformine-type alkaloids. A Grignard/N-acylpyridinium salt reaction of a 4-methoxytetrahydroquinoline is the key carbon-carbon bond-forming step that was used to establish the desired absolute stereochemistry at the C2 position of the target alkaloid. The synthesis features an allylation reaction with an N-acyliminium ion to set the C10 quaternary stereocenter, a mild dissolving-metal cleavage of hindered phenyl carbamates, and an aminoiodocyclization to form the pyrrolidine ring. While this route does not provide the correct C10 stereochemistry, it showcases an efficient method to build analogues with the ring system of this class of alkaloids in 11 steps overall.",10.1021/acs.joc.6b01514,2016-09-14,0.6135583805628942
Angewandte Chemie International Edition,An Expedient Synthesis of a Functionalized Core Structure of Bielschowskysin,"Photons in action: Cascade sequences, brevity, and efficiency are the hallmarks of the synthesis of a functionalized tricyclo[9.3.0.0]tetradecane ring system of the marine natural product bielschowskysin. The synthesis is achieved in five steps, with the key step being an exquisite intramolecular [2+2] photocycloaddition of a macrocyclic precursor (see scheme).",10.1002/anie.201101360,2011-04-26,0.6135543488743256
European Journal of Organic Chemistry,"A Route to (2α,3β,4α)-(±)-2-(Hydroxymethyl)-3,4-pyrrolidinediol Based on the α-Silyloxyallylation of a Glycolaldehyde-Derived Nitrone","A protected form of title compound 6a, whose two enantiomers are known to be potent α-glycosidase inhibitors, was obtained through a five-step synthesis based on two thoroughly diastereo-controlled steps. An anti-selective α-silyloxyallylation of nitrone 9 afforded hydroxylamine 8a which, after O-silylation, was subjected to iodocyclisation to give 5-iodomethylisoxazolidine 7a as a single diastereoisomer. Displacement of iodide by mesylate and hydrogenolysis of mesylate 7b furnished 6b in 20 % overall yield starting from tert-butyldimethylsilyloxyacetaldehyde.",10.1002/(sici)1099-0690(199811)1998:11<2361::aid-ejoc2361>3.0.co;2-7,1998-11-01,0.6135508956025997
Synthesis,"A Convergent Total Synthesis of the Biologically Active Benzofurans Ailanthoidol, Egonol and Homoegonol from Biomass-Derived Eugenol","An efficient, general synthetic protocol for the synthesis of the biologically active benzofurans ailanthoidol, egonol and homoegonol was developed. The key starting material, eugenol, is a naturally occurring and abundant precursor. The protocol, involving sequential acylation and intramolecular Wittig reaction, provides a convenient method for building the benzofuran moiety in good yield.",10.1055/s-0037-1610169,2018-06-28,0.613547239856023
Journal of the American Chemical Society,Concise Total Synthesis of (±)-Marcfortine B,"The marcfortine alkaloids are complex indolic secondary metabolites isolated from various Penicillium sp. and are potent anthelmintic agents. Herein, we report the first total synthesis of marcfortine B. The key features of our synthesis are the use of the carboxylative TMM-cycloaddition to construct the central spirocyclic cyclopentane core and an intramolecular Michael-addition and radical cyclization to access its strained bicyclo[2.2.2]diazaoctane ring system.",10.1021/ja070142u,2007-02-22,0.6135464100993724
Organic Letters,Stereoselective Routes to Hexahydropyrroloindoles and Tetrahydropyrroloquinolines from Activated Aziridines and Electron Deficient 3<i>H</i>-Indoles,"An unprecedented and novel synthetic route to hexahydropyrrolo[2,3- b ]indoles bearing cis -contiguous stereocenters with excellent stereoselectivities (ee of >99%, dr of ≤99:1) has been disclosed that proceeds through the ring opening of activated aziridines with electron deficient 4-substituted indoles followed by a novel cyclization in a domino fashion, thereby obviating the use of 3-substituted indoles as the prerequisite nucleophile. Another efficient synthetic route to tetrahydropyrrolo[4,3,2- de ]quinolines in excellent yields (≤93%) and excellent enantioselectivity (ee of >99%) has been established via ring opening of activated aziridines with 4-bromo-1-methyl-1 H -indole at relatively higher temperatures followed by Cu(I)-catalyzed intramolecular C–N cyclization in the same pot. The stability and the formation of products at different temperatures are explained by computational studies.",10.1021/acs.orglett.2c02354,2022-09-12,0.6135389228518684
Synlett,"Efficient Synthesis of Polysubstituted 1,5-Benzodiazepinone Dipeptide Mimetics via an Ugi-4CR-Ullmann Condensation Sequence","Abstract An efficient three-step synthesis towards 3-amino-1,4-benzodiazepin-2-one derivatives is presented. The versatile Ugi-4-component reaction (Ugi-4CR) and Boc deprotection is followed by a ligand-free Ullmann condensation. This protocol allows the rapid construction of a diverse array of substituted 1,5-benzodiazepinones. Since Ugi-based products are typically limited by their ‘inert’ C-terminal amides, the use of a convertible (‘cleavable’) isocyanide was envisaged and resulted in building blocks that can be made SPPS compatible. To demonstrate the potential of this novel synthetic route, the design and preparation of novel phenylurea-1,5-benzodiazepin-4(5H)-one dipeptide mimetics with potential CCK2-antagonist properties is reported.",10.1055/a-1545-2860,2021-07-06,0.6135375247799406
Journal of Organic Chemistry,Practical Synthesis of a Neuropeptide Y Antagonist via Stereoselective Addition to a Ketene,"[Reaction: see text]. The synthesis of neuropeptide Y antagonist 1, currently under clinical investigation for the treatment of obesity, is described. The convergent synthesis from trans-spirolactone carboxylic acid intermediate 2a and aminopyrazole 3 is predicated on a stereoselective route to the former. The coupling reaction of ethyl 4-oxocyclohexanecarboxylate (10a) with lithiated isonicotinamide 11 was investigated in detail, but even optimized conditions only provided a 45:55 ratio of trans:cis isomers (12a:12b). While selective crystallization schemes were developed to isolate the thermodynamically less stable trans isomer 2a, improved stereocontrol was subsequentially achieved by the application of ketene chemistry. The ketene formation and quench was investigated under a variety of conditions aimed at maximizing the trans:cis ratio. Reacting a mixture of carboxylic acids 2a and 2b with POCl3 in THF, followed by concomitant addition of tert-butyl alcohol in the presence of TMEDA at 35 degrees C provided a 4:1 ratio of trans:cis tert-butyl esters (18a:18b) via in situ ketene formation. Ester hydrolysis, followed by selective crystallization of undesired 2b as the HCl salt, led to isolation of 2a in 47% overall yield. Aminopyrazole intermediate 3 was synthesized via the condensation reaction of 2-fluorophenylhydrazine hydrochloride (4a) with acrylonitrile derivative 5 in 65-70% yield. Coupling of advanced intermediates 2a and 3b via activation with thionyl chloride gave a 92% yield of 1.",10.1021/jo0512709,2005-10-08,0.6135354005281553
Tetrahedron,Synthesis of 3-hydroxyspermidine: An unusual polyamine constituent of cytotoxic marine compounds,"A short, convergent synthesis of the title compound, (±)-N1-(3-aminopropyl)-1,4-diamino-2-butanol 6, was accomplished in 42% overall yield by means of a highly regioselective 1,3-dipolar nitrone cycloaddition.",10.1016/0040-4039(95)01976-o,1995-12-01,0.6135343061679915
Organic Letters,"Design and Synthesis of 5‘-Deoxy-5‘-Phenyladenophostin A, a Highly Potent IP<sub>3</sub> Receptor Ligand<sup>1</sup>","[structure: see text] 5'-Deoxy-5'-phenyladenophostin A (5), designed as a useful IP(3) receptor ligand based on the previous structure-activity relationship studies, was successfully synthesized via two key stereoselective glycosidation steps. This compound proved to be a highly potent IP(3) receptor agonist.",10.1021/ol0602710,2006-03-01,0.6135293808992717
Journal of Organic Chemistry,Application of Palladium(0)-Catalyzed Processes to the Synthesis of Oxazole-Containing Partial Ergot Alkaloids,"Syntheses of the potent 5-HT 1A agonists 2 and 3 were accomplished in several steps from the 6-iodo partial ergoline alkaloid 8 . Disparate tactics available for construction of differentially substituted oxazoles led to the development of new and general methodology critical to the efficient preparations of 2 and 3 . A novel palladium(0)- and copper(I)-cocatalyzed cyanation reaction provided efficient access to the nitrile 10, a key intermediate in the synthesis of 2 . A palladium(0)-catalyzed cross-coupling reaction of 16 with oxazol-2-ylzinc chloride formed the potent 5-HT 1A agonist 3 .",10.1021/jo970374j,1997-12-01,0.6135236658665613
Organic Process Research & Development,"An Efficient Process for Synthesis of 3-(<i>R</i>)-3-(2,3-Dihydrobenzofuran-5-yl)- 1,2,3,4-tetrahydropyrrolo[3,4-<i>b</i>]quinolin-9-one","3-( R )-3-(2,3-Dihydrobenzofuran-5-yl)-1,2,3,4-tetrahydropyrrolo[3,4- b ]quinolin-9-one ( 1 ) is a key intermediate in the synthesis of pyrroloquinolone analogues, a series of highly potent and selective phosphodiesterase 5 (PDE5) inhibitors. Racemic 1-(2,3-dihydrobenzofuran-5-yl)-2,3,4,9-tetrahydro-1 H -β-carboline ( 6, Scheme 2) was prepared by Pictet−Spenger condensation in 84% isolated yield with >97% chemical purity. The desired intermediate, 1-( R )-1-(2,3-dihydrobenzofuran-5-yl)-2,3,4,9-tetrahydro-1 H - β -carboline N -acetyl- d -leucine salt ( 8 ), was obtained in 35% isolated yield with high chiral purity (≥ 97% ee) from the chemical resolution of 6 with N -acetyl- d -leucine ( 7 ). A racemization step was developed for recycling enriched 1-( S) -β-carboline 9 freebase ( 8 / 9, 25 ± 3%/75 ± 3%) to a near racemic mixture ( 8 / 9, 47 ± 1%/53 ± 1%). Furthermore, the resolving reagent 7 was recovered in >76% yield, which, together with the recycled racemic mixture ( 8 / 9, 47 ± 1%/53 ± 1%), afforded 35% more salt 8 after two recycles (≥97.0% ee). The salt 8 was converted to 1-( R )-1-(2,3-dihydrobenzofuran-5-yl)-2-benzyl-2,3,4,9-tetrahydro-1 H -β-carboline ( 10 ) in excellent yield (94%). A modified Winterfeldt oxidation of compound 10 using Aliquat 175 as a phase transfer catalyst produced 3-( R )-2-benzyl-3-(2,3-dihydrobenzofuran-5-yl)-1,2,3,4-tetrahydropyrrolo[3,4- b ]quinolin-9-one ( 12 ) in moderate 42% yield. Hydrogenolysis of compound 12 gave the desired compound 1 in quantitative yield with retention of chiral purity (≥97.0% ee). This efficient, reproducible, economical, and nonchromatography scale-up process could be used to make multikilogram quantities of compound 1 .",10.1021/op050079y,2005-07-28,0.6135149665651061
European Journal of Organic Chemistry,Synthesis of Isotopically Labelled L-Phenylalanine and L-Tyrosine,"A synthetic route to stable-isotope-substituted L-phenylalanine is presented, which allows the introduction of 13C, 15N, and deuterium labels at any position or combination of positions. For labelling of the aromatic ring, a synthetic route to ethyl benzoate (or benzonitrile) has been developed, based on the electrocyclic ring-closure of a 1,6-disubstituted hexatriene system, with in situ aromatization by elimination of one (amino) substituent. Several important (highly isotopically enriched) synthons have been prepared, namely benzonitrile, benzaldehyde, ethyl benzoate, and ethyl diphenyloxyacetate. Labelled L-phenylalanines have been synthesized from both aromatic precursors by initial conversion into sodium phenylpyruvate and subsequent transformation of this intermediate into the L-α-amino acid by an enzymatic reductive amination reaction. In this manner, highly enriched phenylalanines are obtained on the 10-gram scale and with high enantiomeric purities (≥ 99% ee). The method has been validated by the synthesis of [1′-13C]-L-Phe and [2-D]-L-Phe. In addition, two methods are described for the introduction of isotopes into L-tyrosine starting from the isotopically enriched precursors benzonitrile and ethyl benzoate.",10.1002/(sici)1099-0690(199910)1999:10<2609::aid-ejoc2609>3.3.co;2-g,1999-10-01,0.6135113136792293
European Journal of Organic Chemistry,Synthesis of Isotopically Labelled L-Phenylalanine and L-Tyrosine,"A synthetic route to stable-isotope-substituted L-phenylalanine is presented, which allows the introduction of 13C, 15N, and deuterium labels at any position or combination of positions. For labelling of the aromatic ring, a synthetic route to ethyl benzoate (or benzonitrile) has been developed, based on the electrocyclic ring-closure of a 1,6-disubstituted hexatriene system, with in situ aromatization by elimination of one (amino) substituent. Several important (highly isotopically enriched) synthons have been prepared, namely benzonitrile, benzaldehyde, ethyl benzoate, and ethyl diphenyloxyacetate. Labelled L-phenylalanines have been synthesized from both aromatic precursors by initial conversion into sodium phenylpyruvate and subsequent transformation of this intermediate into the L-α-amino acid by an enzymatic reductive amination reaction. In this manner, highly enriched phenylalanines are obtained on the 10-gram scale and with high enantiomeric purities (≥ 99% ee). The method has been validated by the synthesis of [1′-13C]-L-Phe and [2-D]-L-Phe. In addition, two methods are described for the introduction of isotopes into L-tyrosine starting from the isotopically enriched precursors benzonitrile and ethyl benzoate.",10.1002/(sici)1099-0690(199910)1999:10<2609::aid-ejoc2609>3.0.co;2-p,1999-10-01,0.6135113136792293
Journal of the American Chemical Society,Total Synthesis of (−)-Illisimonin A Enabled by Pattern Recognition and Olefin Transposition,"High Resolution Image Download MS PowerPoint Slide We report an asymmetric total synthesis of (−)-illisimonin A, a sesquiterpene natural product with neurotrophic activity. Illisimonin A possesses a unique cage-like 5/5/5/5/5 pentacyclic scaffold containing a trans -pentalene and a norbornane, two highly strained and challenging structural motifs. It also contains seven contiguous fully substituted stereocenters, including three all-carbon quaternary centers, two of which are adjacent. Our synthesis exploits a pattern recognition strategy to identify a 5,6-fused bicyclic intermediate derived from ( S )-carvone in two steps as the starting point and leverages five sequential olefin transposition reactions to decorate the bicyclic carbocycle. Other key steps include a tandem Mukaiyama hydration-translactonization to form the γ-butyrolactone and an intramolecular aldol cyclization to close the cage and finally deliver (−)-illisimonin A in 16 steps.",10.1021/jacs.5c05409,2025-05-13,0.6134960069144855
Synthesis,"Phospha-Michael Reaction on 4H-Chromen-4-one: A Useful Application for the Synthesis of Phosphorated 4-Oxochromanes, 4-Hydroxychromanes, and 4-Oxo-4H-chromenes","Abstract We report here a practical method for the synthesis of dimethyl (4-oxochroman-2-yl)phosphonate and ethyl (4-oxochroman-2-yl)phenylphosphinate through regioselective phospha-Michael addition on chromone followed by the first high diastereoselective reduction with NaBH4 to obtain the novel dimethyl cis-(4-hidroxychroman-2-yl)phosphonate and ethyl cis-(4-hidroxychroman-2-yl)phenylphosphinate, which using the Mitsunobu reaction were converted into trans diastereoisomers. Additionally, dimethyl (4-oxo-chroman-2-yl)phosphonate and ethyl (4-oxochroman-2-yl)phenylphosphinate were transformed into (4-oxo-4H-chromen-2-yl)phosphonic acid and (4-oxo-4H-chromen-2-yl)phenylphosphinic acid, analogues of 4-oxo-4H-chromene-2-carboxylic acid.",10.1055/a-2685-9214,2025-08-18,0.6134936844738921
Tetrahedron,An improved procedure for the preparation of β-thiohydroximates for glucosinolate synthesis,,10.1016/j.tetlet.2011.01.117,2011-02-02,0.6134888049227405
Organic Letters,Total Synthesis of (−)-Bucidarasin A Starting from an Original Chiral Building Block,"The highly stereoselective total synthesis of (-)-bucidarasin A, which also elucidated the absolute structure of its natural form, is described. The total synthesis features effective use of the original chiral building block prepared by us and a series of highly stereoselective reactions, i.e., hydroxy-directed hydrogenation, [4 + 2] cycloaddition of a sterically hindered dienophile, reduction of ketones, formation of the C9 side-chain diene, and formation of the THF moiety bearing two acetyloxy groups.",10.1021/ol502129u,2014-09-05,0.613484724794371
Journal of Organic Chemistry,"Enantioselective Synthesis of 4,5-Dihydropyrroles via Domino Ring-Opening Cyclization (DROC) of <i>N</i>-Activated Aziridines with Malononitrile","An efficient and practical strategy for the synthesis of highly functionalized racemic and non-racemic 4,5-dihydropyrroles via domino ring-opening cyclization (DROC) of activated aziridines with malononitrile in excellent yield and stereoselectivity is described. The reaction serves as a tool for the synthesis of a large variety of substituted 4,5-dihydropyrroles in enantiomerically pure forms.",10.1021/jo302815m,2013-02-07,0.6134798565278442
Tetrahedron,A novel hydroxyalkyl-decyanation of 4-pyridinecarbonitrile: A facile selective synthesis of 4-pyridinemethanols,,10.1016/0040-4039(95)01564-x,1995-10-01,0.6134754688850657
Tetrahedron,A novel aminoalkyl-decyanation of 4-pyridinecarbonitrile with imines: A facile selective synthesis of 4-pyridinemethanamines,,10.1016/0040-4039(96)00455-8,1996-04-01,0.6134754688850657
Tetrahedron,An efficient route to 4-(substituted benzyl)piperidines,,10.1016/j.tetlet.2003.09.075,2003-10-15,0.6134723136655897
Organic Letters,Toward the Synthesis of Spirastrellolide B:  A Synthesis of the C1−C23 Subunit,A synthesis of the C1-C23 subunit of spirastrellolide B is described. The synthesis features two applications of a Kulinkovich-cyclopropanol ring-opening strategy for the coupling of esters with olefins to produce ketones.,10.1021/ol702955m,2008-02-15,0.6134617706456039
Journal of Organic Chemistry,Total Synthesis of (±)-Nisamycin,"N-antibiotic nisamycin that is applicable to other members of this family of antibiotics. The synthesis features a three-step sequence to the epoxyquinol core that serves as a scaffold for the attachment of the polyene side chains. The eastern polyene side chain was constructed via a novel organozirconocene-mediated synthesis. Zirconocene methodology was also applied to the synthesis of the polyene side chains of asukamycin. The southern side chain of nisamycin was introduced via a Stille reaction that employed a vinyl bromo ketone, derived from an acid-sensitive bromo ketal. Pd-mediated coupling of the vinyl bromide with a stannyl TIPS ester gave TIPS-protected nisamycin that was readily converted to the natural product.",10.1021/jo990413m,1999-06-24,0.613458261178981
Organic Letters,"Divergent Total Syntheses of (−)-Lycopladine D, (+)-Fawcettidine, and (+)-Lycoposerramine Q",Enantioselective total syntheses of (+)-fawcettidine and (+)-lycoposerramine Q as well as the first total synthesis of (-)-lycopladine D from a common intermediate have been accomplished by a divergent path. The common intermediate was derived from a Hajos-Parrish-like diketone by a stereoselective Birch reduction and a Suzuki coupling. The synthesis of (-)-lycopladine D featured an allylic oxidation and a biomimetic aminoketalization while the route to (+)-fawcettidine and (+)-lycoposerramine Q highlighted an oxidative rearrangement.,10.1021/ol402906y,2013-11-04,0.613454489285552
Synthesis,Total Synthesis of the Nonenolide Xyolide Using a Regioselective Nucleophilic Epoxide Opening Approach,"The total synthesis of the nonenolide xyolide is described as a convergent synthesis in 16 steps from the commercially available starting material butane-1,4-diol. The key reactions involved are: Sharpless­ asymmetric epoxidation, Pinnick oxidation, acid-mediated nucleophilic regioselective epoxide ring opening, Steglich esterification, and ring-closing metathesis.",10.1055/s-0034-1380780,2015-06-19,0.6134517920580117
Tetrahedron,One step synthesis of sapphyrin and N-confused porphyrin using dipyrromethane,,10.1016/s0040-4039(98)01603-7,1998-10-01,0.6134488512494468
Tetrahedron,Use of t-butyl 4-diethylphosphono-3-oxobutanethioate for tetramic acid synthesis: Total synthesis of the plasmodial pigment fuligorubin A,,10.1016/s0040-4039(00)82204-2,1988-01-01,0.6134441029787316
Synthesis,"Facile Access to 3,4-Disubstituted 2H-Chromenes via Domino [4+2] Annulation","Abstract A highly efficient synthetic route to polysubstituted 2H-chromenes was developed utilizing a domino O-alkylation/intramolecular Horner–Wadsworth–Emmons (HWE) olefination of diarylmethylphosphonates, which were readily accessed via Lewis acid mediated one-pot three-component coupling of aldehydes, phenols, and triethyl phosphite.",10.1055/s-0040-1706089,2020-11-19,0.6134328134469395
Organic Process Research & Development,Development of Scaffold Synthesis for the Preparation of New Insulin-Like Growth Factor 1 Receptor Inhibitors,"The synthesis of new insulin-like growth factor 1 receptor (IGF-1R) inhibitors is reported. The described molecules have a new sulfonyl-indazole structure. We describe the process research and development for the scaffold synthetic procedure in order to provide the large amount of product required for lead optimization, candidate selection, and preclinical studies.",10.1021/op8002536,2009-01-21,0.61343241863615
Journal of Organic Chemistry,Palladium(0)-Catalyzed Coupling of Organozinc Iodide Reagents with Bromopyridines:  Synthesis of Selectively Protected Pyridine-Containing Azamacrocycles,"The synthesis of azamacrocycles in which the ring nitrogens are regioselectively functionalized is described. An organozinc palladium(0)-catalyzed coupling with an appropriately functionalized bromopyridine generated a key intermediate, which was transformed in two steps to a desired precursor and subjected to an intramolecular N-alkylation to effect a macrocyclization affording selectively protected azamacrocycles 1-3.",10.1021/jo0109523,2002-01-17,0.6134316882734319
Organic Letters,Synthesis of the Angiotensin Converting Enzyme Inhibitor (−)-A58365A via an Cycloaddition Reaction,[formula: see text] The angiotensin converting enzyme inhibitor (-)-A58365A (1) was synthesized by a process based on the [3 + 2]-cycloaddition reaction of a phenylsulfonyl-substituted isomünchnone intermediate. The starting material for this process was prepared from L-pyroglutamic acid and involved using a diazo-phenylsulfonyl-substituted pyrrolidine imide. Treatment of the diazoimide with Rh2(OAc)4 in the presence of methyl vinyl ketone afforded a 3-hydroxy-2-pyridone derivative which was subsequently converted to the ACE inhibitor in six additional steps.,10.1021/ol9905497,1999-05-17,0.6134301798787665
Organic Process Research & Development,Development of a Safe and Scalable Amine-to-Nitrone Oxidation:  A Key Step in the Synthesis of R107500,"The stepwise optimization towards a safe, reproducible, and high-yielding oxidation of azepine 2 into the prochiral nitrone 4 is described, with emphasis on the elimination of Davis reagent 3 . m -Chloroperoxybenzoic acid (mCPBA) was found to be an elegant and scalable alternative oxidant regarding safety, yield, and easy workup procedures. Nitrone 4 was obtained in 95% yield and used without purification or isolation in the cycloaddition step to provide oxazolidone 6 in high yield. The process was scaled up successfully to an 800-L scale (60 mol of starting material).",10.1021/op0200569,2002-10-12,0.6134104354445452
Journal of Organic Chemistry,"Highly Stereocontrolled Synthesis of Natural Barbacenic Acid, Novel Bisnorditerpene from <i>Barbacenia </i><i>f</i><i>lava</i>","Barbacenic acid, a bisnorditerpene with five contiguous asymmetric centers (four fully substituted), has been prepared for the first time through a highly stereocontrolled route in 5.2% overall yield from a known octalone. The synthesis serves to define the absolute configuration of the natural product.",10.1021/jo0340049,2003-04-11,0.613395346587093
Organic Process Research & Development,Optimization of the Industrial-Scale Manufacturing Process for Arformoterol through Classical Resolution of Formoterol,"Brovana Inhalation Solution is a sterile, clear, colorless aqueous solution of the tartrate salt of arformoterol. Arformoterol, the R, R -enantiomer of formoterol, is a highly effective medication with improved pharmacodynamic properties, including increased receptor binding affinity and prolonged bronchodilation. This report describes the development of a robust, efficient, cost-effective, and commercially scalable process for the production of the targeted ( R,R )-isomer of formoterol featuring a chiral resolution of inexpensive and readily available formoterol fumarate. This newly developed resolution process proved its efficacy by providing >99.90% chiral pure arformoterol with 74% overall yield.",10.1021/acs.oprd.5c00092,2025-06-07,0.6133903422741787
Synthesis,Synthesis of Chiral α-Aminoalkylpyrimidines Using an Enantioselective Three-Component Reaction,A range of chiral α-aminoalkylpyrimidines has been prepared in a modular fashion in 5 steps with up to 98% ee. The key step is a CuBr-catalyzed enantioselective asymmetric three-component synthesis of propargylic amines.,10.1055/s-2004-829129,2004-07-01,0.6133846278893467
Journal of the American Chemical Society,A Fully Synthetic Route to the Neurotrophic Illicinones:  Syntheses of Tricycloillicinone and Bicycloillicinone Aldehyde,"Tricycloillicinone ( 1 ) and bicycloillicinone asaronacetal ( 2 ) were both isolated from extracts of the wood of Illicium tashiroi . These compounds were found to enhance the action of choline acetyltransferase, which catalyzes the synthesis of acetylcholine from its precursor. Since one of the characteristic symptoms of Alzheimer's disease involves degeneration of cholinergic neurons, resulting in markedly reduced levels of acetylcholine, compounds with the properties of 1 or 2 could well serve as agents in the treatment of such disorders. In this paper, we report the total synthesis of 1 and the construction of the core structure 3 of 2 . The tricycloillicinone synthesis employed a novel strategy to control the regiochemistry of two ortho Claisen rearrangements. A sulfonyl group introduced at C 2 of an allyl group effectively suppressed its unwanted rearrangement to the para position ( 23 → 24 ). Subsequently, ortho Claisen rearrangement was conducted using a reverse O-prenylated derivative 31 to furnish the desired 32, selectively. 32 was used as a common precursor for the syntheses of both 1 and 3 . The application of Corey−Snider oxidative cyclization and the Barton−McCombie deoxygenation provided a direct route to 1 . For bicycloillicinone aldehyde 3, a new tandem reaction using the Et 2 AlCN to construct the cage structure ( 39 → 41 ) was employed. Flexible syntheses of the polycyclic illicinones should provide access to analogous structures for future biological and SAR studies.",10.1021/ja000521m,2000-06-13,0.6133845729260408
Journal of Organic Chemistry,Approach toward the Total Synthesis of Orevactaene. 2. Convergent and Stereoselective Synthesis of the C18−C31 Domain of Orevactaene. Evidence for the Relative Configuration of the Side Chain,"The synthesis of the C18-C31 subunit of orevactaene (1) in an enantioselective and convergent manner is reported. Four chiral centers in the structure (i.e., carbons 23, 25, 32, and 33) have unknown configuration; thus, a modular approach has been devised to link the two stereocenter-containing ends of the structure together via a trisubstituted olefin template to ultimately produce all possible diastereomers of the target. Keys to the success of this approach include (i) an efficient synthesis of four diastereomeric hydrophobic tails (C22-C29) of the molecule with two stereogenic centers at C23 and C25; (ii) the synthesis of three stereodefined trisubstituted olefins 37, 38, and 43 using palladium(0)-catalyzed hydrometalation and metallometalation; and (iii) the convergent assembly of the aforementioned sections by a 'one-pot' lithium/halogen exchange, boron/lithium exchange, borate ester saponification, and Suzuki cross-coupling followed by oxidative deprotection. The sequence provided the desired aldehydes 49 and 50 as single isomers in good yields. Compiled spectroscopic data from the literature and present work provides evidence that the relative configuration of the methyl groups in the side chain of orevactaene may be 1,3-syn, which will be confirmed when the total synthesis has been completed. These results have paved the way for a parallel synthesis approach to prepare all 16 possible stereoisomers of orevactaene so that the relative and absolute stereochemistry of this compound can be determined.",10.1021/jo0201777,2002-06-20,0.6133828415970172
Angewandte Chemie International Edition,Total Synthesis of Isodaphlongamine H by Iridium‐Catalyzed Reductive [3 + 2] Cycloaddition of <i>N‐</i> Hydroxylactam,"The total synthesis of isodaphlongamine H based on a lactam strategy, which enables quick access to complex cyclic amines, is described. The strategy begins with alkylation of a chiral lactam and subsequent N-oxidation via an imino ether to afford the N-hydroxylactam. For the key transformation to functionalize the amide carbonyl, an iridium-catalyzed reductive [3 + 2] cycloaddition of the N-hydroxylactam provides a tricyclic isoxazolidine in a one-pot process. After the coupling reaction with an allylic silane fragment, the total synthesis is accomplished through intramolecular Hosomi-Sakurai allylation to construct a pentacyclic core. The deoxygenated pentacyclic intermediate shows higher cytotoxicity against HeLa and U937 cell lines than isodaphlongamine H, and might become a lead compound for further biological study.",10.1002/anie.202508062,2025-05-06,0.6133818026459796
Organic Letters,Convergent Synthesis of Stereodefined <i>exo</i>-Alkylidene-γ-Lactams from β-Halo Allylic Alcohols,"A convergent process for the assembly of stereodefined mono- and bicyclic exo-alkylidene-gamma-lactams is described that proceeds through the union of beta-halo allylic alcohols, aromatic imines, and CO. Overall, regio- and stereoselective Ti-mediated reductive cross-coupling, followed by Pd-catalyzed carbonylation, can be performed in a one- or two-pot procedure, defining a highly selective three-component coupling process for heterocycle synthesis.",10.1021/ol9022134,2009-10-30,0.6133813602147593
Organic Letters,"First Asymmetric Total Syntheses of Fawcettimine-Type <i>Lycopodium</i> Alkaloids, Lycoposerramine-C and Phlegmariurine-A",A successful asymmetric total synthesis of lycoposerramine-C involving such key steps as a cobalt-mediated Pauson-Khand reaction and vinyl Claisen rearrangement and its biomimetic transformation to phlegmariurine-A are described.,10.1021/ol902437t,2009-11-05,0.6133799410023884
Journal of the American Chemical Society,Unified Total Synthesis of Pyrroloazocine Indole Alkaloids Sheds Light on Their Biosynthetic Relationship,"The total synthesis of seven members of the lapidilectine and grandilodine family of alkaloids has been accomplished in racemic and enantiopure form without protection/deprotection of functional groups. The two key steps, an 8- endo-dig hydroarylation and a 6- exo-trig photoredox cyclization, were catalyzed using gold. A rationale for the formation of the cyclopropane ring of the lundurines is also provided.",10.1021/jacs.7b13484,2018-02-12,0.6133651137269318
Organic Process Research & Development,Development of a Scalable Method for the Synthesis of Ethoxy(pentafluoro)cyclotriphosphazene,"Ethoxy(pentafluoro)cyclophosphazene ( 1 ) exhibits excellent flame retardancy and various biological activities, and there are numerous synthesis methods available. However, most of these methods have certain problems and shortcomings, such as the use of expensive raw materials and toxic and harmful reagents. To address these issues and uncertainties, we reported the development of a facile and sustainable synthesis method of 1, which involves only two concise chemical steps. In this process, the first step contains the reaction of hexachorocyclotriphosphazene ( 3 ) with sodium fluoride to yield hexafluorocyclotriphosphazene ( 2 ). The second step includes ethoxylation using an ethoxylation reagent, ethanol, and sodium hydroxide as an acid-binding agent to produce 1 with good quality and an overall yield of 76%. Several advantages are offered by this new synthetic approach, including good reactivity, high yield, low cost, environmental friendliness, and, finally, being industrially viable. The optimized process has been successfully demonstrated on a large scale to support the development of the new energy electric vehicle industry.",10.1021/acs.oprd.4c00243,2024-11-21,0.6133564822806351
Synlett,"Synthesis of Azepino[4,5-b]indolones by an Intramolecular Cyclization of Unsaturated Tryptamides","A facile general route for the synthesis of azepino[4,5- b ]indolones is presented. The strategy involves a Brønsted acid assisted intramolecular cyclization of unsaturated tryptamides. The methodology developed has been applied to the synthesis of the ABCD tetracyclic core of the natural product tronocarpine.",10.1055/s-0034-1379083,2014-10-02,0.6133491913807477
Organic Letters,An Approach to the Core Structure of Leiodermatolide,The synthesis of the 16-membered core structure of leiodermatolide 40 has been achieved in 26 linear steps starting from (R)-Roche ester. The key steps in the synthesis of 40 are a Stille cross-coupling between two main fragments 11 and 33 having roughly equal size. For the trisubstituted C4/C5 double bond a carbometalation reaction followed by a Suzuki coupling was used. A Yamaguchi macrolactonization furnished macrolactone 39.,10.1021/ol200584a,2011-03-28,0.6133356960608924
Organic Process Research & Development,"A New and Simplified Process for Preparing <i>N</i>-[4-(3,4-Dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenylidene]methanamine and a Telescoped Process for the Synthesis of (1<i>S</i>-<i>cis</i>)-4-(3,4-Dichlorophenol)-1,2,3,4-tetrahydro-<i>N</i>-methyl-1-naphthalenamine Mandelate:  Key Intermediates in the Synthesis of Sertraline Hydrochloride","N -[4-(3,4-Dichlorophenyl)-3,4-dihydro-1(2H)-naphthalenylidene]methanamine, sertraline imine ( 3 ), is an intermediate for the synthesis of Zoloft, sertraline hydrochloride ( 1 ). A cleaner, simpler, and more efficient alternative to the Schiff base-mediated formation of sertraline imine has been developed and is presented in this paper. The condensation reaction between 4-(3,4-dichlorophenyl)-3,4-dihydro-1(2H)-naphthalone, sertraline tetralone ( 2 ), and monomethylamine was carried out in ethanol, without the need for classical dehydrating agent, such as TiCl 4, or more novel approaches, such as molecular sieves, both of which produce hazardous byproducts and solid wastes. The low solubility of the imine 3 in this type of solvent is exploited, such that the reaction equilibrium favorably enhances the imine formation. Furthermore, an improved and highly selective catalytic reduction of 3 with Pd/CaCO 3 catalyst in ethanol as the reaction solvent, followed by the resolution of the racemic cis isomer ( 6 ) with d -(−)-mandelic acid results in a more efficient telescoped commercial process to (1 S - cis )-4-(3,4-dichlorophenol)-1,2,3,4-tetrahydro- N -methyl-1-naphthalen-amine mandelate, sertraline mandelate ( 4 ). This new process has been implemented commercially and eliminates the use of hazardous material such as TiCl 4, significantly reduces undesirable byproducts, reduces the number of intermediate isolations, and improves the overall process yield and productivity on industrial scale.",10.1021/op0341465,2004-04-24,0.6133319325969568
Organic Process Research & Development,An Alternative Indazole Synthesis for Merestinib,"A new synthesis of a key indazole-containing building block for the MET kinase inhibitor merestinib was designed and demonstrated. Crucial to the successful construction of the challenging indazole is an S N Ar reaction, which forges the heterocyclic ring. Continuous processing was applied to two of the five steps: nitration of a benzaldehyde and high-temperature hydrolysis of an aniline to phenol. Compared to a highly developed historical route, the new route shows clear benefits in terms of product quality and potentially manufacturability and robustness.",10.1021/acs.oprd.8b00016,2018-02-21,0.6133272305241256
Tetrahedron,Efficient synthesis of an androgen receptor modulator,,10.1016/j.tetlet.2008.01.114,2008-02-01,0.6133211734072681
Tetrahedron,"Synthesis of 1-amino-1,2,5-trideoxy-2,5-imino-d-mannitol, a novel analogue of the powerful glucosidase inhibitor 2,5-dideoxy-2,5-imino-d-mannitol, via an Amadori rearrangement of 5-azido-5-deoxy-d-glucofuranose",,10.1016/s0040-4039(97)01198-2,1997-08-01,0.6132872642736598
Tetrahedron,"Total synthesis of cyclotheonamide B, a facile route towards analogues",,10.1016/0040-4039(95)01153-9,1995-08-01,0.6132845991775683
Tetrahedron,"Total Synthesis of Cyclotheonamide B, a Facile Route towards Analogues",,10.1016/00404-0399(50)11539-,1995-08-14,0.6132845991775683
Journal of Organic Chemistry,Total Synthesis of (±)-Scopadulin,"The first total synthesis of (+/-)-scopadulin, an aphidicolane diterpene, is described. The core structure (A/B/C/D ring system) was constructed by an initial synthesis of the B/C/D ring system by our reported methods and a subsequent A ring cyclization by intramolecular aldol condensation. A highly stereoselective cyanation of the tetracyclic enone by Et2AlCN gave a trans-fused A/B ring system with a beta-cyanide at C-4. Stereoselective construction of a quaternary carbon at C-4 was achieved by alpha-alkylation of the cyano group and conversion of the sterically hindered cyano group to a methyl group via our novel reaction for conversion of primary aliphatic amines into alcohols. Finally, the total synthesis of (+/-)-scopadulin was accomplished by a highly chemo- and stereoselective methylation at C-16 and modification of the C-4 alpha-functionality. The stereoselectivity observed in the MeTi(O-i-Pr)3-mediated methylation for the generation of a tertiary axial alcohol at C-16 is extremely high.",10.1021/jo015590d,2001-06-16,0.6132832317889322
European Journal of Organic Chemistry,Successive <i>β</i>‐Glycosylations of Tiacumicinone: Formal Total Synthesis of Tiacumicin B and Access to a <scp>d</scp>‐Mannoside Analog,"Abstract A formal total synthesis of the natural macrolide antibiotic tiacumicin B is described featuring successive and selective glycosylations of tiacumicinone. The challenging β‐facial selectivity of these key glycosylation steps was achieved by using noviosyl or rhamnosyl donors equipped with a phenyl sulfoxide leaving group and a 3‐ O ‐picoloyl group ensuring an efficient remote stereodirecting effect. Compared with our former total synthesis, this strategy enables us to save steps and gain access to new analogs. This was demonstrated by the replacement of the rhamnosidic moiety by a d ‐mannose derivative.",10.1002/ejoc.202301098,2023-12-12,0.6132716970264536
Tetrahedron,Efficient and scalable synthesis of thiazole fused benzazepine as a D2 partial agonist,,10.1016/j.tetlet.2012.08.035,2012-08-24,0.6132702081705156
Synthesis,A New Route to Nitrogen Mustards,,10.1055/s-1970-21635,1970-01-01,0.6132654885430435
Tetrahedron,An improved synthesis of substituted cyclopropanone acetals and hemiacetals,,10.1016/s0040-4039(00)81627-5,1983-01-01,0.6132647521295725
Tetrahedron,"Improved synthesis of substituted pyrido[2,3-d]pyrimidinediones",,10.1016/j.tetlet.2011.05.021,2011-05-20,0.6132647521295725
Synthesis,Improved Synthesis of<i>N</i>-Substituted Isopropylideneaziridines,,10.1055/s-1981-29641,1981-01-01,0.6132647521295725
Organic Process Research & Development,Multigram Scale Synthesis of Piperarborenines C-E,"We report the multigram scale synthesis of heterodimeric β-truxinic imides piperarborenines C-E using a catechol-tethered diastereoselective intramolecular [2 + 2] photocycloaddition. Key innovations lie in the use of catechol as a practical auxiliary for the synthesis of homo- and heterodimeric β-truxinates and the use of a UV-LED flow photoreactor in the [2 + 2] step. This approach is highly scalable, requiring a single column purification, no photocatalysts, and no cryogenic conditions.",10.1021/acs.oprd.2c00049,2022-05-26,0.6132624095627031
Tetrahedron,An approach to forskolin an efficient synthesis of a tricyclic lactone intermediate,,10.1016/s0040-4039(00)80411-6,1988-01-01,0.6132554657634014
Organic Process Research & Development,N-Ylide Mediated Synthesis and Resolution of a Chiral Pyrimidinyl Cyclopropane Carboxylic Acid,"High Resolution Image Download MS PowerPoint Slide We report the synthesis of a pyrimidinyl trans -cyclopropane carboxylic acid (rac- 1 ) in 3 steps (58% yield) from 2-chloro-4-methylpyrimidine ( 2 ), and its chiral resolution via recrystallization of the ( S )-1-(1-naphthyl)ethylamine or (+)-abietylamine salts. Following the observation of a palladium-catalyzed conjugate addition of potassium vinyltrifluoroborate to 4-methyl-2-vinylpyrimidine ( 3 ), an efficient, novel cyclopropanation of 3 was developed through reaction with the nitrogen ylide derived from t -butyl bromoacetate and DABCO.",10.1021/acs.oprd.3c00175,2023-08-15,0.6132542108724076
Journal of the American Chemical Society,Characterization and Crystal Structure of a High-Affinity Pentavalent Receptor-Binding Inhibitor for Cholera Toxin and <i>E. </i><i>c</i><i>oli</i> Heat-Labile Enterotoxin,"Multivalent ligand design constitutes an attractive avenue to the inhibition of receptor recognition and other biological events mediated by oligomeric proteins with multiple binding sites. One example is the design of multivalent receptor blockers targeting members of the AB(5) bacterial toxin family. We report here the synthesis and characterization of a pentavalent inhibitor for cholera toxin and Escherichia coli heat-labile enterotoxin. This inhibitor is an advance over the symmetric pentacyclen-derived inhibitor described in our earlier work in that it presents five copies of m-nitrophenyl-alpha-D-galactoside (MNPG) rather than five copies of beta-D-galactose. The approximately 100-fold higher single-site affinity of MNPG for the toxin receptor binding site relative to galactose is found to yield a proportionate increase in the affinity and IC50 measured for the respective pentavalent constructs. We show by dynamic light scattering that inhibition of receptor binding by the pentavalent inhibitor is due to 1:1 inhibitor:toxin association rather than to inhibitor-mediated aggregation. This 1:1 association is in complete agreement with a 1.46 A resolution crystal structure of the pentavalent inhibitor:toxin complex, which shows that the favorable single-site binding interactions of MNPG are retained by the five arms of the 5256 Da pentavalent MNPG-based inhibitor and that the initial segment of the linking groups interacts with the surface of the toxin B pentamer.",10.1021/ja0202560,2002-07-01,0.613251440965247
Tetrahedron,Novel synthesis of the allene moiety of carotenoids via biomimetic photosensitized oxygenation,,10.1016/s0040-4039(01)01405-8,2001-10-01,0.6132459794777759
Journal of Organic Chemistry,Synthesis of the Core Tricyclic Ring Domain of (−)-Schulzeine B,"A formal synthesis of (-)-schulzeine B, a marine natural alkaloid possessing potent antidiabetic activity, has been achieved. A benzo[a]quinolizidin-4-one is a common skeleton of schulzeines (A-C). (-)-Schulzeine B possesses an (S)-stereogenic center at the C-3 carbon. The chiral (3S,11bS)-3-amino-9,11-dimethoxybenzo[a]quinolizidin-4-one has been prepared efficiently from (2-bromo-3,5-dihydroxyphenyl)acetonitrile in 17 steps including (i) a dehydrative intramolecular amination catalyzed by HClO4 and (ii) a proline or boric acid catalyzed transcycloamidation reaction for the construction of the δ-lactam ring.",10.1021/acs.joc.5b01173,2015-07-17,0.6132423923687341
Tetrahedron,A convergent total synthesis of resorcylic acid lactones zeaenol and cochliomycin A,,10.1016/j.tetlet.2022.153777,2022-04-01,0.6132403918984566
Tetrahedron,"A convergent, stereocontrolled total synthesis of isohirsutic acid",,10.1016/s0040-4039(01)85038-3,1972-01-01,0.6132403918984566
Synthesis,"Enantioselective Total Synthesis of the Antifungal Agent (6<i>S</i>)-5,6-Dihydro-6-[(2<i>R</i>)-2-hydroxy-6-phenylhexyl]-2<i>H</i>-pyran-2-one","An enantioselective route for the synthesis of (6S)-5,6-dihydro-6-[(2R)-2-hydroxy-6-phenylhexyl]-2H-pyran-2-one is reported. The synthesis is based on epoxide ring opening with a Grignard reagent and stereoselective reduction employing catecholborane as key reactions.",10.1055/s-2007-990928,2007-12-01,0.6132308122059678
Organic Letters,Total Synthesis of the Natural Product (±)-Dibromophakellin and Analogues,(±)-Dibromophakellin has been synthesized in two steps from a known alkene intermediate. The key step in the synthesis is the NBS olefin activation to facilitate the addition of a guanidine molecule across the double bond.,10.1021/ol300329h,2012-02-24,0.6132160668158323
Organic Letters,Total Synthesis of the Natural Product (±)-Dibromophakellin and Analogues,(±)-Dibromophakellin has been synthesized in two steps from a known alkene intermediate. The key step in the synthesis is the NBS olefin activation to facilitate the addition of a guanidine molecule across the double bond.,10.1021/ol201741r,2011-07-28,0.6132160668158323
Tetrahedron,"A novel one-pot palladium-mediated synthesis of N-[(2-hydroxyphenyl)methyl]-N-(4-phenoxy-3-pyridinyl) acetamide, the precursor to [11C]PBR28, a PET biomarker for the peripheral benzodiazepine receptor",,10.1016/j.tetlet.2010.04.089,2010-04-29,0.6132073810379878
Tetrahedron,"An enantioselective synthesis of the CE ring system of the alkaloids manzamine A, E and F, and ircinal a",,10.1016/0040-4039(95)00296-o,1995-04-01,0.6132053396553387
Synlett,Modular Approaches to Cyclopentanoids and their Heteroanalogs,"Abstract Cyclopentanoids and their derivatives are interesting targets in synthetic organic chemistry due to their extensive applications in various branches of chemical sciences like pharmaceuticals, natural and non-natural products. In view of these applications, several synthetic strategies have been developed in the past three to four decades. In this article, we describe our work towards the synthesis of cyclopentanoids and their heteroanalogs involving diverse synthetic strategies during the past two decades. Among these, photo-thermal olefin metathesis, ring-closing metathesis, ring-rearrangement metathesis, cyclopentane annulation, [2+2+2] cycloaddition and Diels–Alder reactions have been used to assemble cyclopentane rings of diverse architecture. 1 Introduction 2 Synthesis of Spiro[4.4]nonane (A1) Derivatives 3 Synthesis of Octahydropentalene (A2) Derivatives 4 Synthesis of Linear Triquinanes (A3) 5 Synthesis Spiro Triquinanes (A4) 6 Synthesis of Angular Triquinane (A5) Systems 7 Synthesis of Hexahydro-2′H-spiro[cyclopentane-1,1′-pentalene] (A6) Ring System 8 Synthesis of Dispiro[4.1.47.25]tridecane (A7) Ring System 9 Synthesis of Hexahydro-1H-3a,7a-propanoindene Ring System 10 Synthesis of Linear Tetraquinanes (A11 and A12) 11 Synthesis of Tetrahydro-1′H,3′H-dispiro[cyclopentane-1,2′-pentalene-5′,1′′-cyclopentane] (A13) Ring System 12 Synthesis of Decahydro-1H,8H-dicyclopenta[a,h]pentalene (A14) Ring System 13 Synthesis of Dodecahydro-1H-dicyclopenta[a,d]pentalene (A15) Ring System 14 Synthesis of Octahydro-1′H-spiro[cyclopentane-1,2′-cyclopenta[c]pentalene] (A16) Ring System 15 Synthesis of Decahydrospiro[cyclopentane-1,7′-cyclopenta-[a]pentalene] (A17) Ring System 16 Synthesis of Compact Tetraquinane (A18) 17 Synthesis of Higher Polyquinanes 18 Conclusions 19 Acronyms",10.1055/a-1288-8240,2020-10-12,0.6131942486317871
Journal of Organic Chemistry,Formal Total Synthesis of (+)-Lysergic Acid via Zinc(II)-Mediated Regioselective Ring-Opening Reduction of 2-Alkynyl-3-indolyloxirane,"Asymmetric formal synthesis of (+)-lysergic acid was achieved with a reductive ring-opening reaction of chiral 2-alkynyl-3-indolyloxirane with NaBH(3)CN as the key step. With Zn(OTf)(2) as an additive, the ring-opening reaction proceeded regioselectively at the 3-position to give the corresponding propargyl alcohol, which was a precursor of the allenic amide for palladium-catalyzed domino cyclization to construct the ergot alkaloid core structure.",10.1021/jo2008324,2011-05-20,0.6131895992055292
Journal of the American Chemical Society,Circumtrindene:  A Geodesic Dome of Molecular Dimensions. Rational Synthesis of 60 of C<sub>60</sub><sup>1</sup>,"The title compound ( 1 ), which had previously been available in only 0.2% yield by flash vacuum pyrolysis (FVP) of decacyclene ( 2 ) at 1200−1300 °C, has now been prepared in 25−27% yield by FVP of 3,9,15-trichlorodecacyclene ( 5b ) at 1100 °C. The propeller-shape 5b was synthesized by aldol cyclotrimerization of 8-chloro-1(2 H )-acenaphthylenone ( 8b ), which, in turn, was prepared by a simple four-step synthesis from 2-chloronaphthalene. The synthetic strategy demonstrated here, which has improved the yield of circumtrindene ( 1 ) by more than 2 orders of magnitude, should be applicable to the rational synthesis of larger geodesic polyarenes, both open (bowls, baskets, tubes, etc.) and closed (fullerenes).",10.1021/ja993028n,2000-03-01,0.6131893294313862
Tetrahedron,Regioselective Suzuki coupling of benzofuran or benzothiophene boronic acids and dibromo substituted naphthalenes: synthesis of a potent inhibitor of plasminogen activator inhibitor-1,,10.1016/j.tetlet.2006.03.090,2006-04-12,0.6131772397827289
Journal of Organic Chemistry,"Synthesis of 10,11-Dihydro-12-oxo-LTB<sub>4</sub>, a Key Biochemical Intermediate","The first total synthesis of the 5(S)-hydroxy-10,11-dihydro-12-oxo-6(Z),8(E),14(Z)-eicosatrienoic acid (10,11-dihydro-12-oxo-LTB(4)) (3) is reported. This compound is a key pivotal intermediate in the biotransformation of LTB(4) by the so-called ""LTB(4) reductase pathway"".",10.1021/jo9614957,1997-01-01,0.6131762243394084
Synlett,An Operationally Simple and Efficient Synthesis of Orthogonally Protected <scp>l</scp>-<i>threo</i>-β-Hydroxyasparagine,"A synthesis of orthogonally protected L-threo-beta-hydroxyasparagine from L-aspartic acid is reported. Iodocyclization of 3-benzoylaminoaspartic acid provided an intermediate oxazoline dicarboxylate that was efficiently hydrolyzed to L-threo-beta-hydroxyaspartic acid. The synthetic route for conversion of the free beta-hydroxy-alpha-amino acid into the target compound is highly efficient and amenable to preparation various orthogonally protected asparagine derivatives, on a multiple gram scale.",10.1055/s-2007-982544,2007-06-01,0.613173389245835
Journal of Organic Chemistry,Short Enantioselective Total Syntheses of Cheloviolenes A and B and Dendrillolide C via Convergent Fragment Coupling Using a Tertiary Carbon Radical,"The development of a convergent fragment coupling strategy for the enantioselective total syntheses of a group of rearranged spongian diterpenoids that harbor the cis-2,8-dioxabicyclo[3.3.0]octan-3-one unit is described. The key bond disconnection relies on a late-stage fragment coupling between a tertiary carbon radical and an electron-deficient alkene to unite two ring systems and form two new stereocenters, one of which is quaternary, in a stereoselective and efficient manner. This strategy is applied toward scalable 14-15 step syntheses of three rearranged spongian diterpenoids, cheloviolenes A and B, and dendrillolide C.",10.1021/acs.joc.7b02458,2017-11-13,0.6131406785176401
Angewandte Chemie International Edition,Synthesis and Determination of the Absolute Configuration of Cavicularin by a Symmetrization/Asymmetrization Approach,"Taking the strain: The asymmetric total synthesis and stereochemical assignment of (-)-cavicularin, which features a highly strained polycyclophane ring system, has been achieved. The key features of this synthesis are 1) macrocyclization by an SN Ar reaction, 2) group-selective reaction to induce planar chirality in a highly stereoselective manner, and 3) radical transannulation to construct the highly strained ring system.",10.1002/anie.201304929,2013-08-16,0.6131072425614094
Tetrahedron,A short synthetic route to the core structures of otteliones A and B,,10.1016/j.tetlet.2005.06.021,2005-06-30,0.6131068783695405
Synlett,Novel Tocopherol Compounds VII. γ-Tocopherol-5-carboxylic Acid - a Novel Route to γ-Tocopherol,All articles of this category A novel route for the synthesis of γ-tocopherol starting from the readily available vitamin E ( α-tocopherol) has been found. The key step is the photochemical decarboxylation of γ-tocopherol -5-carboxylic acid. α-tocopherol - γ-tocopherol - γ-tocopheroxyl radical - photochemical decarboxylation - MALDI-MS,10.1055/s-1997-730,1997-02-01,0.6131049684542806
Synlett,"Synthesis of a Tetrahydroquino[2,1-c][1,4]benzodiazepine Ring System via Electrochemically Prepared <i>α</i>-Aminonitriles","All articles of this category The synthesis of the 7-amino-5,6,6a,13-tetrahydroquino[2,1-c][1,4]benzodiazepine 7 starting from the readily available 1-(2-nitrobenzyl)-1,2,3,4-tetrahydroquinoline 1 is described. The two key steps are an electrochemical cyanation and a deprotection-cyclization between an amino group and the cyano substituent. [1,4]benzodiazepine - amidine containing heterocycle - α -aminonitrile - t -butoxycarbonylation - electrochemistry",10.1055/s-1998-1696,1998-05-01,0.6131004954842255
Organic Letters,Total Synthesis of (+)-Panacene,"The first total synthesis of the naturally occurring enantiomer of the marine bromoallene (+)-panacene is described. Central to this concise enantioselective synthesis was the use of a Noyori transfer hydrogenation for a Dynamic Kinetic Resolution (DKR) that set the desired absolute stereochemistry. A highly stereoselective Julia coupling was then used to install a Z-configured enyne, which enabled the biomimetic construction of the axially chiral bromoallene.",10.1021/acs.orglett.6b03219,2016-12-02,0.6130973251111421
Synthesis,Multigram Synthesis of a Chiral Substituted Indoline Via Copper-Catalyzed Alkene Aminooxygenation,"(S)-5-Fluoro-2-(2,2,6,6-tetramethylpiperidin-1-yloxymethyl)-1-tosylindoline, a 2-methyleneoxy-substituted chiral indoline, was synthesized on multigram scale using an efficient copper-catalyzed enantioselective intramolecular alkene aminooxygenation. The synthesis is accomplished in four steps and the indoline is obtained in 89% ee (>98% after one recrystallization). Other highlights include efficient gram-scale synthesis of the (4R,5S)-di-Ph-box ligand and efficient separation of a monoallylaniline from its bis(allyl)aniline by-product by distillation under reduced pressure.",10.1055/s-0031-1289762,2012-04-27,0.6130940684234161
European Journal of Organic Chemistry,"One‐Pot Synthesis of 2,7‐Dioxabicyclo[2.2.1]heptanes from Oxoallylsilanes","Abstract A one‐pot high‐yielding synthesis of silylated 2,7‐dioxabicyclo[2.2.1]heptanes from oxoallylsilanes is described. The mechanism of this tandem reaction is a sequential epoxidation of the allylsilane moiety and subsequent intramolecular cyclization. This simple protocol allows the synthesis of epoxy‐bridged tetrahydropyrans from allene in two high‐yielding steps: silylcupration of allene (followed by capture of the intermediate cuprate with enones) and treatment of the oxoallylsilanes thus obtained with MCPBA. However, under the same conditions, oxovinylsilanes yielded epoxysilyl ketones in a very stereoselective manner.",10.1002/ejoc.201101087,2011-10-11,0.6130880398444664
Tetrahedron,Dispiroketals in synthesis (part 2): A new group for the selective protection of diequatorial vicinal diols in carbohydrates.,,10.1016/s0040-4039(00)61281-9,1992-08-01,0.613086552142404
Organic Letters,Synthetic Studies on (+)-Manzamine A: Stereoselective Synthesis of the Tetracyclic Core Framework,The stereoselective synthesis of the tetracyclic intermediate 3 for (+)-manzamine A (1) has been achieved. The key features of this stereoselective synthesis of 3 are the Rh-catalyzed asymmetric hydrogenation and a diastereoselective intermolecular Diels-Alder reaction. The 8-membered ring is efficiently constructed utilizing our Ns-strategy.,10.1021/ol801111r,2008-07-03,0.6130862016678635
Organic Letters,"Total Synthesis and Determination of the Absolute Configuration of Naturally Occurring Mangromicin A, with Potent Antitrypanosomal Activity","An enantioselective total synthesis of (+)-mangromicin A has been accomplished. The tetrahydrofuran ring of mangromicin A, possessing a tetrasubstituted carbon center, was constructed by Mukaiyama-type vinylogous alkylation via a cyclic oxocarbenium intermediate derived from a γ-hydroxy ketone with ideal stereoselectivity, and the 4-hydroxydihydropyrone scaffold was generated via Dieckmann cyclization at a late stage of the total synthesis. The reliable asymmetric synthesis of (+)-mangromicin A has revealed the absolute configuration of naturally occurring mangromicin A.",10.1021/acs.orglett.6b03512,2016-12-12,0.6130757426193834
European Journal of Organic Chemistry,"Towards the Total Synthesis of Marineosin A: Construction of the Macrocyclic Pyrrole and an Advanced, Functionalized Spiroaminal Model","Abstract Herein, we describe the enantioselective construction of the 12‐membered macrocyclic pyrrole core of marineosin A in 5.1 % overall yield from ( S )‐propylene oxide. The route features a key Stetter reaction to install a 1,4‐diketone, which is subjected to Paal–Knorr pyrrole synthesis and ring‐closing metathesis to afford the macrocycle. A divergence point in the synthetic scheme also enabled access to a highly functionalized spiroaminal model system through an acid‐mediated hydroxy oxo amide cyclization strategy.",10.1002/ejoc.201300643,2013-06-04,0.6130675528574563
Angewandte Chemie International Edition,Total Synthesis of the Marine Natural Product <i>rac</i>‐Dibromophakellstatin,"The pyrrole-imidazole alkaloid dibromophakellstatin (1) from the marine sponge Phakellia mauritiana was synthesized in only five steps starting from L-prolinol. The key step of the synthesis is the direct annulation of the imidazolinone ring to a pyrrolopyrazinone precursor by employing an ethoxycarbonylnitrene generated in situ. Samarium diiodide proved to be the best choice for the chemoselective, stepwise deprotection of the resulting tetracycle. Ts=toluenesulfonyl.",10.1002/anie.200462252,2005-03-04,0.6130615911056598
Angewandte Chemie International Edition,The Enantioselective Total Synthesis of Bisquinolizidine Alkaloids: A Modular “Inside‐Out” Approach,"Abstract Bisquinolizidine alkaloids are characterized by a chiral bispidine core (3,7‐diazabicyclo[3.3.1]nonane) to which combinations of an α,N‐fused 2‐pyridone, an endo‐ or exo‐α,N‐annulated piperidin(on)e, and an exo‐allyl substituent are attached. We developed a modular “inside‐out” approach that permits access to most members of this class. Its applicability was proven in the asymmetric synthesis of 21 natural bisquinolizidine alkaloids, among them more than ten first enantioselective total syntheses. Key steps are the first successful preparation of both enantiomers of C 2 ‐symmetric 2,6‐dioxobispidine by desymmetrization of a 2,4,6,8‐tetraoxo precursor, the construction of the α,N‐fused 2‐pyridone by using an enamine‐bromoacrylic acid strategy, and the installation of endo‐ or, optionally, exo‐annulated piperidin(on)es.",10.1002/anie.201712852,2018-01-23,0.6130524900358993
Tetrahedron,New total synthesis of (±)-chuangxinmycin,,10.1016/s0040-4039(97)00174-3,1997-03-01,0.6130410258628551
Tetrahedron,"l-α-Phosphatidyl-d-myo-inositol 3,5-bisphosphate: total synthesis of a new inositol phospholipid via myo-inositol orthoacetate",,10.1016/s0040-4039(98)01422-1,1998-09-01,0.6130410258628551
Tetrahedron,"A new total synthesis of an indolo[3,2-j]phenanthridine alkaloid calothrixin B",,10.1016/j.tetlet.2005.06.042,2005-07-02,0.6130410258628551
Tetrahedron,"First total synthesis of new diglycosides, neohancoside A, and B from Cynanchum hancockianum",,10.1016/0040-4039(96)00750-2,1996-06-01,0.6130410258628551
Tetrahedron,A new total synthesis of 2-pupukeanone,,10.1016/s0040-4039(97)00298-0,1997-03-01,0.6130410258628551
Tetrahedron,New total synthesis of bikaverin,,10.1016/s0040-4039(00)78863-0,1992-05-01,0.6130410258628551
Tetrahedron,A new total synthesis of equilin,,10.1016/s0040-4039(00)90319-8,1966-01-01,0.6130410258628551
Tetrahedron,A new total synthesis of dl-sirenin,,10.1016/s0040-4039(00)81697-4,1983-01-01,0.6130410258628551
Tetrahedron,"First total synthesis of a new pyrrolizidine alkaloid, amphorogynine A",,10.1016/s0040-4039(03)00070-4,2003-02-01,0.6130410258628551
Tetrahedron,A new total synthesis of pentenomycin,,10.1016/s0040-4039(01)01099-1,2001-08-01,0.6130410258628551
Tetrahedron,A new total synthesis of (±)-norprezizanone,,10.1016/s0040-4039(00)61567-8,1993-11-01,0.6130410258628551
Tetrahedron,A new total synthesis of (±) steganone,,10.1016/s0040-4039(01)93559-2,1979-01-01,0.6130410258628551
Tetrahedron,A new total synthesis of (±)-oestrone,,10.1016/j.tetlet.2004.03.166,2004-04-22,0.6130410258628551
Tetrahedron,New total synthesis of (+)-cystothiazole A,,10.1016/s0040-4039(01)02207-9,2002-01-01,0.6130410258628551
Tetrahedron,"Total Synthesis of Nephilatoxin-7 (NPTX-7), a New Neurotoxin of Joro Spider (Nephila clavata)",,10.1016/00404-0399(50)0979m-,1995-07-17,0.6130410258628551
Tetrahedron,"Total synthesis of Nephilatoxin-7 (NPTX-7), a new neurotoxin of Joro spider (Nephila clavata)",,10.1016/0040-4039(95)00979-m,1995-07-01,0.6130410258628551
Tetrahedron,A new total synthesis of (±) steganone,,10.1016/s0040-4039(01)92428-1,1981-01-01,0.6130410258628551
Tetrahedron,"Total synthesis of 8-desoxy-isocaespitol, A new polyhalogenated sesquiterpene from",,10.1016/s0040-4039(00)71409-2,1980-01-01,0.6130410258628551
Tetrahedron,New total synthesis of equilenin and estrone,,10.1016/s0040-4039(00)87355-4,1982-01-01,0.6130410258628551
Tetrahedron,"New total synthesis of (±)-herbertene, (±)-β-herbertenol and (±)-herbertenediol",,10.1016/s0040-4039(00)01298-3,2000-09-01,0.6130410258628551
Tetrahedron,The total synthesis of the new sesquiterpenoid (±)-fulvanin 1 / Sollasin a,,10.1016/0040-4039(95)00321-3,1995-04-01,0.6130410258628551
Journal of Organic Chemistry,Modular Total Synthesis of <i>iso</i>-Archazolids and Archazologs,"Full details on the design, development, and successful implementation of suitable synthetic strategies directed toward the total synthesis of iso -archazolids and archazologs are reported. Both a biomimetic and a multistep total synthesis of iso -archazolid B, the most potent and least abundant archazolid, are described. The bioinspired conversion from archazolid B was realized by a high-yielding 1,8-Diazabicyclo[5.4.0]undec-7-ene catalyzed one-step double-bond shift. A highly stereoselective total synthesis was accomplished in 25 steps, involving a sequence of highly stereoselective aldol reactions, an efficient aldol condensation to forge two elaborate fragments, and a challenging ring-closing metathesis macrocyclization with an unusual Stewart–Grubbs catalyst. These strategies proved to be generally useful and could be successfully implemented for the preparation of three novel iso -archazolids as well as five novel archazologs, lacking the thiazole side chain. A wide variety of further archazolids and archazologs may now be targeted for exploration of the promising anticancer potential of these polyketide macrolides.",10.1021/acs.joc.1c00946,2021-07-23,0.6130269164407192
Tetrahedron,Total synthesis of a dibromotyrosine alkaloid inhibitor of mycothiol S-conjugate amidase,,10.1016/j.tetlet.2003.10.117,2003-12-02,0.6130159980155054
Journal of Organic Chemistry,"A General Enantioselective Approach to Jasmonoid Fragrances:  Synthesis of (+)-(1<i>R</i>,2<i>S</i>)-Methyl Dihydrojasmonate and (+)-(1<i>R</i>,2<i>S</i>)-Magnolione","Methyl dihydrojasmonate 1 and magnolione 3 are of both academic and industrial interest. In this paper, we describe a flexible, high-yielding route to diastereomerically pure (+)-cis-(1R,2S)-methyl dihydrojasmonate 1 and the first synthesis of (+)-cis-(1R,2S)-magnolione 3, both with enantiomeric excesses up to 93%. The two syntheses diverged from the same advanced intermediate 5, readily available from the enantioenriched hydroxymethyl delta-lactone (-)-(3aS,4S,6aR)-6. The olfactory properties of (1R,2S)-1 and (1R,2S)-3 are reported.",10.1021/jo050423p,2005-05-07,0.6130139560432945
Organic Letters,"Concise, Convergent Syntheses of (±)-Trichostatin A Utilizing a Pd-Catalyzed Ketone Enolate α-Alkenylation Reaction","Two concise, convergent syntheses of (±)-trichostatin A (1), a potent histone deacetylase inhibitor, have been accomplished. The key step in both is a Pd-catalyzed α-alkenylation reaction between ketone 2 and either dienyl bromide 3 or alkenyl bromide 9 using a modification of cross-coupling conditions described by Negishi and Hartwig. A brief investigation has shown the potential utility of a Ni-catalyzed version of this reaction. The overall synthetic routes are short and amenable to scaleup, providing access to trichostatin A via trichostatic acid as a direct precursor.",10.1021/ol200964m,2011-06-21,0.6130112464984643
Tetrahedron,A high yield total synthesis of dl-4-isoavenaciolide,,10.1016/s0040-4039(00)91068-2,1975-01-01,0.6129924000297234
Synthesis,"Facile and Efficient Synthesis of 7,10-Dihydroxy-6H-pyrazolo[4,5,1-de]acridin-6-one via Hypervalent Iodine Oxidation","All articles of this category An improved synthetic procedure for 5,8-dibromo-7,10-dihydroxy-2-methyl-6 H -pyrazolo[4,5,1- de ]acridin-6-one (4) , an intermediate of a novel class of antitumor agents, was developed. An effective introduction of a hydroxy group to the C10 of 5,8-dibromo-7-hydroxy-2-methyl-6 H -pyrazolo[4,5,1- de ]acridin-6-one (2b) was accomplished in two steps via the oxidation of 2b to the corresponding quinone using hypervalent iodine reagent in an acidic medium, followed by reduction of the resulting quinone upon treatment with aqueous sodium hydrosulfite. pyrazoloacridine derivative - hypervalent iodine oxidation - quinone intermediate of antitumor agent - fused heterocyclic compound",10.1055/s-1997-1398,1997-06-01,0.6129826865124229
Synthesis,Efficient Synthesis of Octaalkyloxy-o-quaterphenyls via Base-Induced Biaryl Coupling,"All articles of this category Octamethoxy- o -quaterphenyl ( 8a ) was prepared in three steps from 4-bromo-1,2-dimethoxybenzene ( 5a ) employing two base-mediated biaryl couplings. Demethylation of 8a followed by alkylation with decyl bromide gave the tetradecyloxy- o -quaterphenyl ( 8c ). biaryl coupling - o -quaterphenyl - alkyllithiums",10.1055/s-1999-3412,1999-03-01,0.612950416898409
Journal of Organic Chemistry,"Total Synthesis of Leptosperol B through Stereocontrolled Intramolecular 1,4-Addition to Construct the Octahydronaphthalene Framework","Leptosperol B, possessing a unique octahydronaphthalene framework and 5-substituted aromatic ring, was isolated from the leaves of Leptospermum scoparium in 2020. The asymmetric total synthesis of leptosperol B was accomplished in 12 steps from (−)-menthone. The efficient synthetic scheme involves regioselective hydration and stereocontrolled intramolecular 1,4-addition to construct the octahydronaphthalene skeleton, followed by the introduction of the 5-substituted aromatic ring.",10.1021/acs.joc.2c03017,2023-02-16,0.6129383720428063
Organic Process Research & Development,Development of Scalable Synthesis of Chiral Tetralol via Hydrogen Borrowing and Dynamic Kinetic Resolution,"Herein, we describe a two-step alkylation and asymmetric transfer hydrogenation telescope process for the synthesis of an enantioenriched substituted tetralol, a key intermediate in the synthesis of active pharmaceutical ingredient udifitimod (BMS-986166). A hydrogen borrowing alkylation catalyzed by an iridium catalyst was developed to replace an asymmetric alkylation that utilized an alkyl iodide with a costly stoichiometric chiral auxiliary under cryogenic conditions. In the following step, construction of the key stereocenter on the tetralin core was enabled by dynamic kinetic resolution using Ru-catalyzed asymmetric transfer hydrogenation. Process optimization allowed for a telescoped process that delivered the chiral alcohol product with high yield, purity, and enantio- and diastereoselectivity as well as controlled levels of residual metal content acceptable for downstream processing.",10.1021/acs.oprd.5c00090,2025-06-02,0.6129272533033341
Tetrahedron,Synthesis of the endothelin converting enzyme inhibitor phosphoramidon,,10.1016/0040-4039(95)00024-7,1995-02-01,0.6129265185569965
Tetrahedron,Synthesis of two isotopically labeled versions of NEDD8-activating enzyme (NAE) inhibitor,,10.1016/j.tetlet.2011.02.033,2011-02-13,0.6129265185569965
Angewandte Chemie International Edition,"Asymmetric Synthesis of Bioactive Hydrodibenzofuran Alkaloids: (−)‐Lycoramine, (−)‐Galanthamine, and (+)‐Lunarine",Divergent route: a direct C-C bond-forming approach to the key aryl-substituted all-carbon quaternary stereogenic center present in bioactive hydrodibenzofuran alkaloids has been discovered. This approach involves an unprecedented organocatalytic enantioselective Michael addition of α-cyanoketones with acrylates and was used in a novel and divergent synthetic strategy for the title compounds in asymmetric fashion.,10.1002/anie.201103198,2011-07-11,0.6129077901634508
Organic Letters,Total Synthesis of Herboxidiene/GEX 1A,"A convergent enantioselective synthesis of herboxidiene/GEX 1A (1) is described that features a double stereodifferentiating crotylation, [4 + 2] annulation, and a silicon-based sp2-sp2 cross-coupling to assemble the conjugated diene.",10.1021/ol701427k,2007-07-13,0.6129057581549239
Journal of the American Chemical Society,The Daphniphyllum Alkaloids: Total Synthesis of (−)-Calyciphylline N,"Presented here is a full account on the development of a strategy culminating in the first total synthesis of the architecturally complex daphniphyllum alkaloid, (-)-calyciphylline N. Highlights of the approach include a highly diastereoselective, intramolecular Diels-Alder reaction of a silicon-tethered acrylate; an efficient Stille carbonylation of a sterically encumbered vinyl triflate; a one-pot Nazarov cyclization/proto-desilylation sequence; and the chemoselective hydrogenation of a fully substituted diene ester.",10.1021/ja503899t,2015-03-10,0.6129047113381989
Journal of the American Chemical Society,Total Synthesis of (±)-Aplykurodinone-1: Traceless Stereochemical Guidance,"The total synthesis of the highly degraded steroidal natural product, aplykurodinone-1 (1), has been accomplished. Key features include a one-flask hydrolysis/retro-aldol/iodolactonization sequence to excise the C(8) hydroxymethylene functionality with retention of stereochemistry and the stereoselective installation of the C(13) methyl group through hydrogenation with homogeneous catalyst.",10.1021/ja1035495,2010-06-01,0.6129046884534862
Organic Letters,Convergent Synthesis of the ABCDEF-Ring System of Yessotoxin and Adriatoxin,"[formula: see text] The convergent synthesis of the ABCDEF-ring system of yessotoxin and adriatoxin was accomplished. This efficient convergent strategy was performed on the basis of the coupling of the acetylide of the A-ring and the triflate of the DEF-ring, oxidation of the alkyne to diketone, intramolecular diacetalization, and stereoselective reduction of the diacetal with Et3SiH-TMSOTf.",10.1021/ol026804w,2002-09-28,0.6128903510245299
Tetrahedron,An improved synthesis of yohimbine dieckmann ring closure of unsaturated diesters,,10.1016/s0040-4039(01)97572-0,1971-01-01,0.6128891218726943
Journal of the American Chemical Society,Kedarcidin Chromophore:  Synthesis of Its Proposed Structure and Evidence for a Stereochemical Revision,"A convergent, enantioselective synthesis of the proposed structure of kedarcidin chromophore ( 1 ) is described. The route is 24 steps in the longest linear sequence (beginning with the commercial reagent 2,3- O -isopropylidene- d -erythronolactone) with an average yield of 75% per step (overall yield: 0.1%). Our 1 H NMR data for 1 do not coincide with the data reported for kedarcidin chromophore. We have re-analyzed the original data and here propose a stereochemical revision at position C10, the site of attachment of the l -mycarose carbohydrate residue to the chromophore core (structure 2 ).",10.1021/ja071205b,2007-04-07,0.612880418184662
Journal of Organic Chemistry,Sulfinyl Moiety as an Internal Nucleophile. 1. Efficient Stereoselective Synthesis of Fragment A of Cryptophycin 3,"A novel, efficient, and stereoselective synthesis of fragment A of cryptophycin 3 is disclosed. The key step involves the regio- and stereoselective transformation of an unsaturated ester to a bromohydrin via anchimeric assistance by the sulfinyl group.",10.1021/jo026802p,2003-05-16,0.6128801927602882
Tetrahedron,"Cycloaddition of a 1,2-diaza-1,3-butadiene to phenylpropiolic acid: an efficient route to pyridazinoquinolone derivatives",,10.1016/j.tetlet.2004.08.165,2004-09-30,0.6128797283073313
Organic Process Research & Development,Facile Preparation of 3-(1-Piperazinyl)-1H-indazoles,"Pre-clinical evaluation of a potential antipsychotic agent required a convenient synthesis of 3-(1-piperazinyl)-1H-indazole derivatives. Improvements of the original preparation provided a five-step sequence to an unsubstituted piperazine intermediate, with a 67% overall yield. All intermediates were isolated by filtration.",10.1021/op0002242,2001-01-26,0.612879684312731
Journal of Organic Chemistry,Synthesis of Enantiomerically Pure Stereomers of Rosaprostol,"Enantiopure stereomers of rosaprostol 1, an antiulcer drug, were synthesized from diastereomeric building blocks (-)-5a and (+)-5b. Conversion of (-)-5a into rosaprostol stereomer (-)-(1S,2R,5R)-1a was accomplished in nine steps in 18% overall yield. In this sequence, fully diastereoselective hydrogeneration of the endocyclic carbon double bond in the cyclopentenone ring was key, generating a new stereogenic center (C-2 in 1a). C-5 epimeric rosaprostol (-)-(1S,2R,5S)-1b was obtained from (-)-1a in 72% yield by a two-reaction sequence involving methylation and one-pot Mitsunobu esterification-hydrolysis.",10.1021/acs.joc.5b01749,2015-09-10,0.6128791622301873
Organic Letters,Bioinspired Total Synthesis of 3-<i>epi</i>-Junipercedrol,"A bioinspired total synthesis of 3- epi -junipercedrol, which contains a strained tricyclo[5.2.2.0 3,7 ]undecane allo -cedrane framework and five stereocenters, was accomplished via an effective anionic semipinacol rearrangement of a tricyclic cedrane mesylate. The corresponding cedrane precursor was synthesized efficiently by employing the reductive oxy-Nazarov cyclization and an intramolecular aldol condensation as the key steps. This synthetic approach provided a further evidence for the biogenetic relationship between the typical cedrane and allo -cedrane sesquiterpenoids.",10.1021/acs.orglett.4c02877,2024-08-27,0.612871732031848
Organic Letters,"Synthesis of Tricyclic 4-Chloro-pyrimido[4,5-<i>b</i>][1,4]benzodiazepines","[reaction: see text] A novel methodology was developed for the efficient synthesis of 4-chloro-pyrimido[4,5-b][1,4]benzodiazepines. The key is the intramolecular Friedel-Crafts cyclization of 5-amino-4-(N-substituted)anilino-6-chloropyrimidine with either a carboxylic acid or its derivatives to construct the 4-chloro-pyrimido[4,5-b][1,4]benzodiazepine core. Subsequent nucleophilic substitution allows the introduction of one more diversity point in the target molecules. This strategy provides an efficient method to access a library of compounds based on privileged substructures that are of great interest in drug discovery.",10.1021/ol050181f,2005-03-15,0.6128707981800462
Synthesis,"One-Pot Synthesis of Trisubstituted Monomethylated Benzene-1,3-diols via a Michael Addition-Dieckmann Cyclization Sequence from Methyl (<i>E</i>)-3-Methoxy-4-methoxycarbonylbut-2-enoate Anion and Methyl Alkynoates and Its Application to the Total Synthesis of Nidulol","The reaction of methyl (E)-3-methoxy-4-methoxycarbonylbut-2-enoate (1) with a number of methyl alkynoates under appropriate conditions gave the monomethylated trisubstituted resorcinol derivatives 3 in a regiocontrolled manner, via a Michael addition-Dieckmann cyclization sequence in one pot. The resorcinol 3d, prepared in this manner, was used as the starting material for a three step, highly efficient (54% from 3d) synthesis of the bioactive fungal metabolite nidulol (4).",10.1055/s-2005-872082,2005-01-01,0.6128619828615877
Synlett,Total Synthesis of (+)-Aspicilin from d-Mannitol,"The total synthesis of the 18-membered lichen macrolide, (+)-aspicilin, has been accomplished utilizing the Swern oxidation, Masamune-Roush olefination, and ring-closing metathesis of a trienic ester as key steps. d-Mannitol has been utilized as the chiral pool material for the construction of the olefinic aldehyde and the Jacobsen hydrolytic kinetic resolution has been employed for the construction of the olefinic phosphonate ester.",10.1055/s-0029-1217974,2009-09-09,0.6128575767805632
Synlett,Palladium Catalyzed Synthesis of the Furanoterpene Ircinin-4,"A flexible entry into 2,4-disubstituted furan derivatives is outlined employing sulfonium salt 1 as a well accessible starting material. Condensation of the sulfur ylide derived from 1 with alde-hydes, palladium catalyzed opening of the vinyloxirane thus formed, and a final oxidative cyclization of the furan ring constitute the key steps of this method. Its utility is exemplified by the first to-tal synthesis of the marine natural product ircinin-4 (2).",10.1055/s-1999-2534,1999-01-01,0.6128521020125246
Synthesis,"A Facile Synthesis of 1,1′-Spirobi(3<i>H</i>,3′<i>H</i>)isobenzofurans","The synthesis of a series of aryl 5,5-spiroketals containing a 1,1′-spirobi(3H,3′H)isobenzofuran ring system is reported. The key step involves addition of an aryllithium derived from a protected bromobenzyl alcohol to a phthalide; this is followed by deprotection of the benzyl alcohol and acid-catalysed cyclisation. © Georg Thieme Verlag Stuttgart.",10.1055/s-2007-965911,2007-02-22,0.6128323499279408
Journal of Organic Chemistry,Progress toward a Peptidomimetic of Laminin-Derived Pentapeptide YIGSR:  Synthesis of the Unique Tricyclic Core Structure,"The peptide sequence YIGSR, a segment of the basement membrane matrix glycoprotein laminin, has been identified as a key component in tumor cell invasion. Guided by extensive NMR work and de novo design algorithms, a nonpeptide mimetic of this pentapeptide was identified as a lead candidate for synthesis. The target displays the key amino acid side chains from a novel tricyclic scaffold. The first synthesis of this unique scaffold is completed in 11 steps and 7% overall yield.",10.1021/jo025847n,2002-07-25,0.6128319709746652
Organic Letters,Total Synthesis of Applanatumol B,"The first total synthesis of the tricyclic meroterpenoid applanatumol B, isolated from Ganoderma applanatum, was accomplished in 14 steps from 2,5-dimethoxybenzaldehyde and 4-pentyn-1-ol. The synthetic features include an intramolecular Morita–Baylis–Hillman reaction, a stereoselective Michael addition, and efficient construction of the tricyclic skeleton under acidic conditions involving epimerization at the α-position of the ketone.",10.1021/acs.orglett.9b01901,2019-07-05,0.6128316067830109
Organic Letters,Improved Protein Kinase C Affinity through Final Step Diversification of a Simplified Salicylate-Derived Bryostatin Analog Scaffold,"Bryostatin 1, in clinical trials or preclinical development for cancer, Alzheimer's disease, and a first-of-its-kind strategy for HIV/AIDS eradication, is neither readily available nor optimally suited for clinical use. In preceding work, we disclosed a new class of simplified bryostatin analogs designed for ease of access and tunable activity. Here we describe a final step diversification strategy that provides, in only 25 synthetic steps, simplified and tunable analogs with bryostatin-like PKC modulatory activities.",10.1021/ol502492b,2014-09-19,0.6128301550722346
Angewandte Chemie International Edition,Total Synthesis of Sanglifehrin A,"The immunosuppressive agent sanglifehrin A has been prepared for the first time by total synthesis. The construction of the macrocyclic unit of the target molecule was achieved through a selective intramolecular Stille coupling, and the spirolactam unit by Paterson-aldol reactions. The final steps involve an intermolecular Stille coupling and the opening of the internal acetal unit. This convergent synthesis opens the way for the synthesis of libraries of novel sanglifehrin analogues for biological screening.",10.1002/(sici)1521-3773(19990816)38:16<2447::aid-anie2447>3.0.co;2-o,1999-08-16,0.6128290078041072
Angewandte Chemie International Edition,Total Synthesis of Sanglifehrin A,"The immunosuppressive agent sanglifehrin A has been prepared for the first time by total synthesis. The construction of the macrocyclic unit of the target molecule was achieved through a selective intramolecular Stille coupling, and the spirolactam unit by Paterson–aldol reactions. The final steps involve an intermolecular Stille coupling and the opening of the internal acetal unit. This convergent synthesis opens the way for the synthesis of libraries of novel sanglifehrin analogues for biological screening.",10.1002/(sici)1521-3773(19990816)38:16<2447::aid-anie2447>3.3.co;2-f,1999-08-16,0.6128290078041072
European Journal of Organic Chemistry,Synthesis of Pyranonucleoside‐6′‐triphosphates through the <i>cyclo</i>Sal‐Method,Abstract The high yielding synthesis of pyranonucleoside‐6′‐triphosphates by using the cyclo Sal‐method is described. Synthesis of the activated cyclo Sal‐pyranonucleoside‐6′‐phosphate triesters was achieved by applying a synthetic route that had been developed for the synthesis of cyclo Sal‐(glycopyranosyl‐6)‐phosphates by us. The route involved regioselective 6′‐ tert ‐butyldimethylsilyl protection and exchange of the silyl protecting group by the fluorenylmethyloxycarbonyl (Fmoc) group. The 6′‐Fmoc‐protected derivatives were selectively converted into the cyclo Sal‐triester. These were then very efficiently converted into triphosphates by a “titration‐like” reaction with pyrophosphate. Simple purification by first ion exchange followed by reversed phase (RP) column chromatography afforded the triphosphates in very good yields.,10.1002/ejoc.201402047,2014-04-14,0.6128266230290181
Organic Letters,Catalysis Driven Six-Step Synthesis of Apratoxin A Key Polyketide Fragment,"Apratoxin A is a potent anticancer natural product whose key polyketide fragment constitutes a considerable challenge for organic synthesis, with five prior syntheses requiring 12 to 20 steps for its preparation. By combining different redox-economical catalytic stereoselective transformations, the key polyketide fragment could be rapidly prepared. Followed by a site-selective protection of the diol, this strategy enables the preparation of the apratoxin A fragment in only six steps, representing the shortest route to this polyketide.",10.1021/acs.orglett.2c02482,2022-09-08,0.6128084032439066
Tetrahedron,"Synthesis and revised structure of the o-succinylbenzoic acid coenzyme a ester, an intermediate in menaquinone biosynthesis",,10.1016/s0040-4039(00)98315-1,1985-01-01,0.612803190685688
Synthesis,New Highly Efficient Stereoselective Synthesis of d-threo-PDMP,"Starting from a suitably functionalized aziridine, a highly efficient stereoselective synthesis of (1R,2R)-phenyl-2-decanoylamino- 3-morpholinopropan-1-ol (D-threo-PDMP) is described. The approach, based on the ring expansion of the aziridine ring to oxazoline, could be applicable to the synthesis of many analogues with different amide chains and sugar mimic portions.",10.1055/s-0030-1260225,2011-09-27,0.6128026015324317
Angewandte Chemie International Edition,Total Synthesis of Spirastrellolide A Methyl Ester—Part 2: Subunit Union and Completion of the Synthesis,"Succumbing to synthesis: The stereocontrolled total synthesis of spirastrellolide A methyl ester is reported. The union of two key C1–C16 and C17–C40 subunits is followed by macrolactonization and late-stage side chain attachment by a cross-metathesis reaction and a π-allyl Stille coupling reaction with a C43–C47 stannane, thus confirming the 46R configuration. The full configuration and conformation of the 38-membered macrolide is revealed by single-crystal X-ray analysis of an advanced pentaol intermediate.",10.1002/anie.200705566,2008-02-28,0.6127747118106208
Tetrahedron,"A direct synthesis of 2-arylbenzocyclobutenol, a potential intermediate for podophyllotoxin synthesis: Use of lda for benzyne formation and trapping",,10.1016/s0040-4039(00)85200-4,1986-01-01,0.612774008226803
Synlett,An Efficient Synthesis of Aminocyclopentitols via the Stereoselective Amination of Polybenzyl Ethers Using Chlorosulfonyl Isocyanate,"An efficient stereoselective route for the preparation of stereoisomeric aminocyclopentitols 3-5 was achieved using a six-step sequence starting from the corresponding d-sugars. Key steps of the synthesis of the title compounds involved the regioselective and diastereoselective amination of cinnamylic 1,2-anti- or 1,2-syn-tribenzyl ethers using chlorosulfonyl isocyanate (CSI), intramolecular olefin metathesis, and diastereoselective dihydroxylation.",10.1055/s-2007-984518,2007-06-25,0.612761938304964
Angewandte Chemie International Edition,Synthesis of the FGHI Ring System of Azaspiracid,"As a causative agent of food poisonings, azaspiracid (1), a novel marine toxin isolated from the mussel Mytilus edulis, challenges the synthetic chemist with an intricate array of acetal and ketal structures. The construction of the FGHI ring system of azaspiracid was achieved by means of a key BF3⋅Et2O-catalyzed cyclization to form the HI spirocycle. A final chemoselective intramolecular ketalization with Hg(OAc)2 formed the G ring, to afford the N-protected FGHI as a single diastereomer.",10.1002/1521-3773(20010401)40:7<1262::aid-anie1262>3.0.co;2-9,2001-04-01,0.6127614785398402
Angewandte Chemie International Edition,Synthesis of the FGHI Ring System of Azaspiracid,"As a causative agent of food poisonings, azaspiracid (1), a novel marine toxin isolated from the mussel Mytilus edulis, challenges the synthetic chemist with an intricate array of acetal and ketal structures. The construction of the FGHI ring system of azaspiracid was achieved by means of a key BF3⋅Et2O-catalyzed cyclization to form the HI spirocycle. A final chemoselective intramolecular ketalization with Hg(OAc)2 formed the G ring, to afford the N-protected FGHI as a single diastereomer.",10.1002/1521-3773(20010401)40:7<1262::aid-anie1262>3.3.co;2-0,2001-04-01,0.6127614785398402
Journal of the American Chemical Society,"A Short Enantioselective Pathway for the Synthesis of the Anti-Influenza Neuramidase Inhibitor Oseltamivir from 1,3-Butadiene and Acrylic Acid","A short synthetic pathway has been developed for the synthesis of oseltamivir (1) or the enantiomer (ent-1). The intermediates and conditions for this process are summarized in Scheme 1. The synthesis provides a number of advantages: (1) use of inexpensive and abundant starting materials; (2) complete enantio-, regio-, and diastereocontrol; (3) avoidance of explosive, azide-type intermediates; (4) good overall yield (ca. 30%, still not completely optimized); and (5) scalability.",10.1021/ja0616433,2006-04-25,0.6127568579651739
Tetrahedron,"A rapid route for the preparation of pyrimido[5,4-d]- and pyrido[3,2-d]oxazoles",,10.1016/j.tetlet.2015.03.082,2015-04-11,0.612740810885705
European Journal of Organic Chemistry,Synthesis of ( <i>S</i> )‐ and ( <i>R</i> )‐Harmicine from Proline: An Approach Toward Tetrahydro‐β‐carbolines,"Abstract ( S )‐ and ( R )‐Harmicine were synthesized from L ‐ and D ‐proline, respectively. This chiral pool synthesis constitutes a new approach towards C1 substituted tetrahydro‐β‐carbolines. The developed route makes use of the 9‐phenyl‐9‐fluorenyl protecting group strategy of amino acids to prevent racemization of the vulnerable α‐amino carbonyl stereocenter. Enantiopure harmicine (&gt; 99 % ee ) was obtained in nine steps from commercially available starting material. The synthesis was performed without the use of any silica gel flash chromatography.",10.1002/ejoc.201301903,2014-02-12,0.612737058047852
Journal of Organic Chemistry,"Sulfinimine-Mediated Asymmetric Synthesis of (<i>R</i>)-(4-Methoxy-3,5-dihydroxyphenyl)glycine:  The Central Amino Acid of Vancomycin and Related Agents","The sulfinimine asymmetric Strecker synthesis, the addition of ethyl aluminum cyano alkoxide, “EtAl(OR)CN”, to sulfinimine 10, has been applied to a concise highly efficient four-step enantioselective synthesis of ( R )-(4-methoxy-3,5-dihydroxyphenyl)glycine ( 3 ) and its derivatives in >97% ee. These epimerization-sensitive arylglycines are precursors of the key central amino acid of vancomycin and related glycopeptide antibiotics.",10.1021/jo972076s,1998-02-20,0.6127352438517085
Synlett,Synthesis and Properties of a Buckybowl/Buckyball Dyad,"In this work, we describe the synthesis of a molecule in which fullerene C 60 is covalently attached to a bowl-shaped polycyclic aromatic hydrocarbon, corannulene. The developed synthetic route is comprised of four linear steps with isolated yields ranging from 41–91%. The first three steps relate to the preparation of a hydrazone derivative of corannulene carrying a butyric acid methyl ester group. This key compound generates a reactive diazo moiety under base-induced decomposition process. The generated diazoalkane then adds to the C 60 molecule to furnish the targeted corannulene-C 61 -butyric acid methyl ester (CCBM) molecule. This compound is structurally characterized by NMR spectroscopy and mass spectrometry, whereas material properties are determined with the help of optical absorption spectroscopy and cyclic voltammetry. Finally, some preliminary aspects on its application are examined in a poly(3-hexyl thiophene)-based photovoltaic device.",10.1055/s-0035-1562462,2016-07-05,0.6127333034116673
Journal of Organic Chemistry,Synthesis of (+)-Ambrisentan via Chiral Ketone-Catalyzed Asymmetric Epoxidation,"The synthesis of optically pure (+)-ambrisentan has been achieved from 3,3-diphenylacrylate in four steps with 53% overall yield and >99% ee at the >100 g scale without column purification. The chiral epoxide intermediate was prepared via asymmetric epoxidation with a fructose-derived diacetate ketone as catalyst.",10.1021/jo201927m,2011-11-18,0.612725425909026
Synthesis,One-Step Synthesis of α-Amido-α-methoxy β-lactams as Cephamycin Analogs,,10.1055/s-1982-29816,1982-01-01,0.6127188350699871
Tetrahedron,"New Strategy for the Synthesis of the Taxane Diterpenes : Formation of the BC-Rings of Taxol via a [5+2]-Pyrylium Ylide-Alkene Cyclization, Ring Expansion Strategy",,10.1016/00404-0399(50)1083t-,1995-07-24,0.6127122840663025
Tetrahedron,"New strategy for the synthesis of the taxane diterpenes: Formation of the BC-rings of taxol via a [5+2]-pyrylium ylide-alkene cyclization, ring expansion strategy",,10.1016/0040-4039(95)01083-t,1995-07-01,0.6127122840663025
Journal of Organic Chemistry,New Chiral Pool Approach to Anthracyclinones. The Stereoselective Synthesis of Idarubicinone,"In the present work, a new chiral pool approach has been developed for the synthesis of anthracyclinones. Thus, enone 8, readily available from l-rhamnose, has been converted via addition of 2,5-dimethoxybenzyllithium to the carbonyl group and a series of six reactions into a suitably protected aldehyde 21. The SnCl(4)-promoted stereospecific cyclization of the latter afforded enantiopure key intermediate 22. Silylation of benzylic hydroxyl of 21 followed by anodic oxidation and selective hydrolysis gave ketoacetals 25 and 26 to which 3-cyano-1(3H)-isobenzofuranone 27 was annelated. Removal of the isopropylidene group in the resulting 28, subsequent oxidation of the C(13) hydroxyl and full deprotection led to idarubicinone (4).",10.1021/jo026354l,2003-02-20,0.6127046923037692
Organic Letters,A Macrocyclic β-Iodoallenolate Intermediate Is Key: Synthesis of the ABD Core of Phomactin A,"An enantioselective strategy for the synthesis of phomactin natural products is described. The Lewis acid triggered cyclization of a β-iodoallenolate embedded in a 12-membered macrocycle was used to obtain a highly functionalized bicyclo[9.3.1]pentadecane in good yield and high diastereoselectivity. This iodoenone contains the substituents of the AD ring system of the phomactin family of natural products, appropriate for further functionalization. Synthesis of the oxadecalin core of phomactin A from the AD iodoenone intermediate was achieved. In this unusual strategy, rings A and B are both fashioned within a macrocyclic precursor.",10.1021/ol3017116,2012-08-02,0.6127043321172552
European Journal of Organic Chemistry,"Synthesis of 2,4‐Disubstituted Pyrimidin‐5‐yl <i>C</i>‐2′‐Deoxyribonucleosides by Sequential Regioselective Reactions of 2,4‐Dichloropyrimidine Nucleosides","Abstract A new modular synthesis of diverse 2,4‐disubstituted pyrimidin‐5‐yl C ‐2′‐deoxyribonucleosides by sequential regioselective reactions of 2,6‐dichloropyrimidin‐5‐yl C‐nucleosides was developed. The intermediate was prepared by the Heck coupling of 2,6‐dichloro‐5‐iodopyrimidine with glycal followed by desilylation and reduction. Its mild nucleophilic substitutions or Fe‐catalyzed cross‐coupling with MeMgCl proceeded regioselectively at position 4, whereas at elevated temperatures or with excess of MeMgCl, double substitution occurred. The 2‐chloro‐4‐substituted intermediates undergo another substitution or coupling to afford 2,4‐disubstituted derivatives.",10.1002/ejoc.201000164,2010-03-30,0.6126835134426483
European Journal of Organic Chemistry,A Concise Total Synthesis of (+)‐Heliotridine,"Abstract A practical synthesis of the necine base (+)‐heliotridine ( 1 ) is reported here. The present total synthesis is based on the highly selective 1,3‐dipolar cycloaddition of ( S )‐3‐ tert ‐butoxypyrroline N ‐oxide ( 2 ) to the commercially available ethyl 4‐bromocrotonate, followed by a suitable elaboration of the adduct. The synthesis gives a 17% overall yield from nitrone 2 . (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2003)",10.1002/ejoc.200300405,2003-11-01,0.6126750450287843
Organic Process Research & Development,Scale-Up of an Enantioselective Overman Rearrangement for an Asymmetric Synthesis of a Glycine Transporter 1 Inhibitor,"An enantioselective Overman 3,3-sigmatropic rearrangement on a quinuclidine skeleton was developed for the pilot-plant synthesis of a glycine transporter 1 inhibitor. The first stereocenter was produced by a Ru-catalyzed asymmetric transfer hydrogenation process followed by chirality transfer using the Overman rearrangement. The second stereocenter was generated by a diastereoselective hydrogenation reaction.",10.1021/op200378r,2012-01-15,0.6126699694009178
Journal of the American Chemical Society,Asymmetric Total Synthesis of Dendrobatid Alkaloid 251F,"The dendrobatid alkaloid (-)-251F was synthesized. The key steps of the synthesis were (1) an asymmetric Diels-Alder reaction to establish four of the necessary stereocenters in the target, (2) a ring-opening/ring-closing metathesis reaction to establish a key [3.3.0] bicyclic intermediate, and (3) an intramolecular Schmidt reaction.",10.1021/ja027113y,2002-08-01,0.6126532037818893
Tetrahedron,Total synthesis of altohyrtin A (spongistatin 1): an alternative synthesis of the CD-spiroacetal subunit,,10.1016/s0040-4039(02)00527-0,2002-04-01,0.6126502021384096
Journal of Organic Chemistry,Furanophane Transannular Diels−Alder Approach to (+)-Chatancin:  An Asymmetric Total Synthesis of (+)-Anhydrochatancin,"(+)-anhydrochatancin was synthesized while attempting an enantioselective total synthesis of (+)-chatancin. The presented route constitutes the furanophane approach, one of the two ways of proposed biosynthesis which may involve transannular Diels-Alder (TADA) reaction to link this diterpene biogenetically to the furanocembranoids. Highlights of the synthetic work include the assembly of chiral, acyclic, trisubstituted furan 28 via a coupling of aldehyde 10 and dilithiofuroic acid 11, a macrocyclization to furanophane 29E via ring-closing metathesis, a TADA reaction to reach tetracyclic intermediate 4, and a hydride shift mediated oxygen transposition as a final rearrangement to the target. Unfortunately, the strongly acidic condition required for the last step allows only the isolation of anhydrochatancin 30 due to the acid sensitivity of chatancin 1.",10.1021/jo034123o,2003-03-28,0.6126424108749214
Synlett,Improved Synthesis of Quinacridine Derivatives,International audience,10.1055/s-2006-932465,2006-01-01,0.6126151167523888
Tetrahedron,"Enantioselective synthesis of (1S,3S,7R)-3-methyl-α-himachalene, the sex pheromone of the sandfly Lutzomyia longipalpis from Jacobina, Brazil",,10.1016/s0040-4039(00)00831-5,2000-07-01,0.6126133551857017
Tetrahedron,Enantioselective synthesis of (R)- and (S)-4-[(methoxycarbonyl)-methyl]-2-azetidinones from D-glyceraldehyde acetonide,,10.1016/s0040-4039(00)88082-x,1983-01-01,0.6126133551857017
Journal of the American Chemical Society,Enantioselective Synthesis of (−)-Gilbertine via a Cationic Cascade Cyclization,"Described is the first enantioselective synthesis of (-)-gilbertine (2), a member of the uleine-type family, and the determination of the absolute configuration of this natural product is reported. The key step employs a cationic cascade reaction for a tetrahydropyrane and piperidine ring formation and the construction of the pentacyclic framework in one step. The synthetic strategy utilizes the Shibasaki reaction to build up the first stereogenic center. A formylation reaction of a 3-substituted cyclohexanone derivative was achieved, giving only the desired regioisomer. The Japp-Klingemann Fischer indole protocol was used successfully as a convergent synthetic approach for the construction of the desired tetrahydrocarbazole (20). Furthermore, an unexpected behavior of this 2,3-disubstituted cyclohexanone derivative during an epimerization process was investigated, resulting in different chemical behavior of the enantiomers and the racemate. The diastereomeric resolution was achieved via the cationic cascade reaction, demonstrating the versatility of this approach. Significantly, the synthetic 17-step sequence was easy to execute, giving (-)-gilbertine in 5.5% overall yield.",10.1021/ja0399021,2004-03-01,0.6126106747417299
Organic Letters,Leveraging Alkyne–Oximium Cyclization for the Stereoselective Synthesis of Isoxazolidine,"A TMSOTf-mediated highly diastereoselective synthesis of isoxazolidine bearing three contiguous stereocenters is described. This method utilizes O -propargyl hydroxylamines as a novel building block for the rapid assembly of the isoxazolidines via alkyne–oximium cyclization. The strategy could be used in the synthesis of enantiomerically enriched isoxazolidines. Reductive cleavage of the N–O bond efficiently gives the corresponding 1,3-aminodiols with precise control over all stereocenters formed.",10.1021/acs.orglett.2c03483,2022-11-28,0.6126043763240218
Journal of the American Chemical Society,"Synthesis and Reaction of [(Tp<sup><i>i</i>Pr<sub>2</sub></sup>)LnH<sub>2</sub>]<sub>3</sub> (Ln = Y, Lu) with CO: Trinuclear Cluster-Bound Propenolate en Route to Selective Formation of Propene","The use of the Tp(iPr(2)) ligand led to the straightforward and high-yield synthesis of rare examples of trinuclear monoligand lanthanide dihydrides, [(Tp(iPr(2)))LnH(2)](3) (Ln = Y, Lu). The Y complex was found to mediate the hydrogenation and coupling of carbon monoxide with exclusive formation of propene via the intermediacy of a cluster-bound propenolate ligand.",10.1021/ja905679k,2009-12-16,0.6126016651414062
Journal of Organic Chemistry,Asymmetric Synthesis of Fused Bicyclic α-Amino Acids Having a Hexahydro-cyclopenta[<i>c</i>]pyridine Skeleton via Intramolecular Pauson−Khand Reaction of 1-Sulfonimidoyl-Substituted 5-Azaoct-1-en-7-ynes,"An asymmetric synthesis of fused bicyclic amino acids having a hexahydro-cyclopenta[c]pyridine skeleton and carrying besides an enone structural element a substituent at the beta-position is described. The key steps of the synthesis are a highly selective allylation of N-tert-butylsulfonyl imino ester with bis(allylsulfoximine)titanium complexes and a highly diastereoselective Pauson-Khand cycloaddition of sulfonimidoyl-substituted gamma,delta-unsaturated alpha-amino acid esters carrying a substituent at the beta-position and a propargyl group at the N-atom. The cyclization is accompanied by a reductive cleavage of the sulfoximine group of the primary cyclization product. Surprisingly, the removal of the sulfoximine group proceeds with inversion of the configuration at the S-atom and gives N-methyl-phenylsulfinamide with >/=98% ee. Deprotection of the bicyclic N-tert-butylsulfonyl-protected amino acid ester was accomplished through treatment with CF(3)SO(3)H under anhydrous conditions. The enantio- and diastereomerically pure sulfoximine-substituted gamma,delta-unsaturated alpha-amino acid esters used as starting material were obtained through a highly regio- and diastereoselective allylation of N-tert-butylsulfonyl imino ester with acyclic bis(allylsulfoximine)titanium complexes, described previously.",10.1021/jo030171x,2003-09-26,0.6125869438628124
Tetrahedron,"Synthesis of the new ring system 2-oxo-[1,4]oxazino[3,2-e]indole, heteroanalogue of Angelicin",,10.1016/j.tetlet.2009.05.007,2009-05-10,0.6125822732881003
Journal of the American Chemical Society,Total Synthesis of (±)-Scopadulcic Acid B,The first total synthesis of a scopadulan diterpene is described. The key step is a double Heck cyclization of dienyl aryl iodide 8 to form tetracyclic enones 24 and 25 in 80−85% combined yield.,10.1021/ja972427k,1997-12-17,0.61258018483229
Organic Letters,Synthesis of the C1–C10 Fragment of Madeirolide A,The synthesis of a fully elaborated C1-C10 fragment of madeirolide A has been achieved via a strategy based on a series of stereospecific processes. The concise synthetic route also features an iridium-catalyzed visible light induced radical cyclization for construction of the THP ring and a palladium-catalyzed glycosylation for formation of the α-cineruloside linkage.,10.1021/acs.orglett.6b00777,2016-04-14,0.6125778834058366
Tetrahedron,"Synthetic studies directed toward guianolides: an organoiron route to the 5,7,5 tricyclic ring system",,10.1016/j.tetlet.2008.12.051,2008-12-25,0.6125775278495627
Synthesis,"A Short and Efficient Synthesis of 4,5-Disubstituted-1-pentenes",(opens in new window) Buy Article (opens in new window) Permissions and Reprints (opens in new window) All articles of this category (opens in new window) A one step synthesis of 5-chloro-4-hydroxy-1-pentene(65%) and 5-bromo-4-hydroxy-1-pentene (81%) was developed. Treatment of epibromohydrin or epichlorohydrin at -73°C with a reagent prepared from vinylmagnesium bromide and a catalytic amount of copper(I) bromide gave the desired products. 5-Bromo-4-hydroxy-1-pentene was cleanly converted to 4.5-epoxy-1-pentene in 99% yield by treatment with potassium hydroxide. A number of derivatives of 5-bromo-4-hydroxy-1-pentene are described.,10.1055/s-1986-31594,1986-01-01,0.6125632863956841
Organic Letters,Oxamidation of Unsaturated <i>O</i>-Alkyl Hydroxamates: Synthesis of the Madangamine Diazatricylic (ABC Rings) Skeleton,"A novel approach to the diazatricyclic madangamine ABC ring system and the synthesis of an advanced, differentially protected intermediate for the synthesis of madangamine D is reported. Central to the success of this approach is the iodine(III)-mediated intramolecular oxamidation of an unsaturated O- methyl hydroxamate, a π–N + -type cyclization which proceeds in high yield and with complete regioselectivity to generate the 2-azabicyclo[3.3.1]nonane (morphan) system encompassing rings A and C.",10.1021/acs.orglett.7b03283,2017-11-28,0.612544163807899
Organic Letters,Second-Generation Total Synthesis of Prorocentin,"After a recent total synthesis had resolved all issues surrounding the constitution and stereostructure of prorocentin, it was possible to devise a new approach aiming at an improved supply of this scarce marine natural product; this compound is a cometabolite of the prototypical phosphatase inhibitor okadaic acid but still awaits detailed biological profiling. The revised entry starts from 2-deoxy-d-glucose; keys to success were a telescoped hemiacetal reduction/acetal cleavage and an exquisitely selective gold/Brønsted acid-cocatalyzed spiroacetalization.",10.1021/acs.orglett.3c01720,2023-06-26,0.6125389425362008
Tetrahedron,New synthetic intermediate for trans-8-methylhydrindanones,,10.1016/s0040-4039(00)97374-x,1990-01-01,0.6125097064521697
Synlett,Total Synthesis of Largazole,"The stereocontrolled total synthesis of largazole was accomplished, unambiguously confirming its structure. Key steps included the use of the Nagao thiazolidinethione auxiliary for a diastereoselective acetate aldol reaction, thiazoline-thiazole formation, and macrolactamization by use of the Mukaiyama reagent.",10.1055/s-2008-1078270,2008-08-21,0.6125068484700993
European Journal of Organic Chemistry,"Total Synthesis of Sulfated Glycosphingolipid SM1a, a Kind of Human Epithelial Carcinoma Antigen","Abstract A highly efficient and practical total synthesis of the sulfated ganglioside SM1a, a kind of human epithelial carcinoma antigen identified in mammalian kidney, has been accomplished for the first time. The characteristic sequence of SM1a, β‐ D ‐Gal p ‐(1→3)‐β‐ D ‐NHAcGal p ‐(1→4)‐β‐ D ‐(3‐ O ‐sulfate)‐Gal p ‐(1→4)‐β‐ D ‐Glc p ‐ceramide was assembled by a [3+2] convergent approach. A key trisaccharide building block was formed from a new galactose acceptor 7 containing a potential sulfated site, GalNHTroc donor 6 , and galactose donor 4 . The cyclic glucosyl ceramide was glycosylated with trisaccharide trichloroacetimidate 2 to give the protected ganglioside backbone in good yield. Selective sulfonation at the 3‐OH of the Gal residue followed by global deprotection gave the target molecule SM1a.",10.1002/ejoc.201403296,2014-12-09,0.6125048357482298
Tetrahedron,Synthetic studies on azadirachtin (Part 3): Asymmetric synthesis of the tricyclic dihydrofuran moiety of azadirachtin,,10.1016/s0040-4039(99)00040-4,1999-03-01,0.6125008345122863
Angewandte Chemie International Edition,Asymmetric Alkaloid Synthesis: A One‐Pot Organocatalytic Reaction to Quinolizidine Derivatives,"One pot+two steps=three stereocenters: A short enantioselective synthesis to access the indolo[2,3a]quinolizidine and the benzo[a]quinolizidine skeleton has been developed (see scheme; TMS=trimethylsilyl, R1=aromatic, R2=3-indoyl or 3,4-dimethoxyphenyl). The sequence involves an organocatalytic conjugate addition and subsequent acid-catalyzed cyclization of the acyliminium ion.",10.1002/anie.200805130,2008-12-19,0.6124893857608765
European Journal of Organic Chemistry,Multigram Synthesis of 3‐Azabicyclo[3.1.1]heptane Derivatives Including Bicyclic Thalidomide Analogs,"Abstract An efficient approach to the multigram synthesis of 3‐azabicyclo[3.1.1]heptanes is described. The method relied on the intramolecular imide formation in the properly 1,3‐functionalized cyclobutane derivative. In turn, the latter compound was obtained via the diastereoselective Strecker reaction of readily accessible 3‐oxocyclobutanecarboxylate. The resulting synthetic intermediate – 1‐amino‐3‐azabicyclo[3.1.1]heptane‐2,4‐dione – was used to synthesize several monoprotected bicyclic diamines valuable as building blocks for medicinal chemistry, as well as a series of bridged analogs of Thalidomide, a known anticancer drug and a component of proteolysis‐targeting chimeras (PROTACs).",10.1002/ejoc.202400938,2024-12-23,0.6124884897249816
Organic Process Research & Development,"Facile Synthesis of 5,6-Dimethoxy-1-tetralone","A facile synthesis of 5,6-dimethoxy-1-tetralone, a key intermediate in the synthesis of an antidepressant compound, ABT-200, was developed from the inexpensive starting material guaiacol.",10.1021/op970111r,1998-12-29,0.6124822539696619
Organic Letters,Development of an Approach to the Synthesis of the ABC Ring System of Hemibrevetoxin B,"An efficient approach for the synthesis of a model of the ABC ring system of Hemibrevetoxin B is described. Key features include a ring expansion to yield the ring C oxepane, the reduction of a 2-furyl ketone with high levels of 1,3-stereocontrol, and an Achmatowicz oxidative ring expansion to yield the ring A tetrahydropyran. All seven stereogenic centers present in the model compound were controlled with high levels (>98:<2) of diastereoselectivity.",10.1021/ol0614323,2006-08-19,0.6124737484215003
Synlett,Stereoselective Synthesis of an Immunomodulator (+)-Conagenin Using Dirhodium(II)-Catalyzed C-H Amination and Chelation-Controlled Reductions as Key Steps,Stereoselective synthesis of an immunomodulator (+)-conagenin from commercially available optically active methyl 3-hydroxy-2-methylpropanoate was achieved using dirhodium(II)-catalyzed C-H amination and chelation-controlled reductions as key steps.,10.1055/s-2006-933145,2006-03-14,0.6124720861147517
Synlett,One-Step Synthesis of 3-Thioacetylsulfolane,A one-step synthesis of (S)-3-thioacetylsulfolane is described. Reaction of 3-sulfolene with thiolacetic acid in the presence of AIBN or Ph3SiSH under basic conditions gave racemic 3-thioacetylsulfolane in 30-32% yield. Enantiomerically pure (S)-3-thioacetylsulfolane was obtained by chiral chromatography.,10.1055/s-0031-1290089,2011-12-05,0.6124617465583836
Organic Letters,Asymmetric Total Synthesis of Antiochic Acid,The first asymmetric total synthesis of antiochic acid using bioinspired polyene cyclization strategy is described. Both good yield and good asymmetric induction were obtained.,10.1021/ol800499p,2008-04-26,0.6124613344624046
Synthesis,An Improved Synthesis of <i>N</i>-Isocyanoiminotriphenylphosphorane and Its Use in the Preparation of Diazoketones,"An improved synthesis of N-isocyanoiminotriphenylphosphorane is reported. This reagent is a safe, stable, solid alternative to diazomethane and TMS-diazomethane in the Arndt-Eistert synthesis of diazoketones.",10.1055/s-2004-834928,2004-12-08,0.6124603047578827
Synlett,"Stereo- and Regioselective Synthesis of (E,E)-Dienes: Evolution from the Transition-Metal-Catalyzed Cross-Coupling to Titanium Alkoxide-Based Alkyne–Alkyne Reductive Coupling","Abstract The pursuit of step- and atom-economy in natural product and complex molecule syntheses continuously inspires the development of synthetic methodologies. In this context, to enable efficient synthesis of (E,E)-dienes as common structural subunits in natural products, our lab has established robust protocols based on modified Negishi cross-couplings and evolved them to more concise titanium-mediated alkyne–alkyne reductive coupling. In this review, we summarize the natural product synthesis driven methodology development and their applications in the total synthesis of complex molecules, focusing on the studies from our laboratory. 1 Introduction 2 Transition-Metal-Catalyzed Cross-Coupling in Natural Product Synthesis 2.1 Synthesis of Branched Trisubstituted Conjugated Dienes by Negishi Coupling 2.2 Stereo- and Regiocontrolled Synthesis of Branched Trisubstituted Conjugated Dienes by Modified Negishi Coupling 2.3 Enantioselective Total Synthesis of Reveromycin B by Drouet &amp; Theodorakis 2.4 Enantioselective Synthesis of the Protein Phosphatase Inhibitor (–)-Motuporin by Hu &amp; Panek 2.5 Total Synthesis of (–)-Callystatin A by Langille &amp; Panek 2.6 Total Synthesis of Brevisamide by Lee &amp; Panek 3 Titanium Alkoxide-Mediated Reductive Coupling in Natural Product Synthesis 3.1 Titanium Alkoxide-Mediated Alkyne–Alkyne Reductive Coupling 3.2 Total Synthesis of Callystatin A by Reichard &amp; Micalizio 3.3 Total Synthesis of (–)-Virginiamycin M2 by Wu &amp; Panek 3.4 Total Synthesis of Nuclear Factor of Activated T-Cells-68 (NFAT-68) by Cai &amp; Panek 3.5 Titanium Alkoxide-Based Regioselective Alkyne–Alkyne Reductive Coupling Mediated by in situ Generated Arylamidate 4 Summary",10.1055/a-1977-1006,2022-11-11,0.6124543573054714
Tetrahedron,"A total synthesis of C-nor D-homosteroids of the A → B → C → D type, involving a reductive alkylation step for construction of the d-ring",,10.1016/s0040-4039(00)84593-1,1986-01-01,0.6124543216353263
Journal of the American Chemical Society,Biomimetic Total Syntheses of Flinderoles B and C,"A simple and efficient biomimetic synthesis of pyrrolo[1,2-a]indoles using a highly stereo- and regioselective [3 + 2] reaction cascade was developed and then further applied in the first total synthesis of flinderoles B and C, which proceeded in 17.2% yield over the longest linear sequence of 11 steps.",10.1021/ja1116974,2011-02-11,0.612454032308574
European Journal of Organic Chemistry,"Asymmetric Synthesis of 2,3‐Dihydrofurans by One‐Pot Michael Addition/I<sub>2</sub>‐Mediated Cyclization","A highly efficient strategy for the asymmetric enantio‐ and diastereoselective synthesis of dihydrofuran derivatives was developed. The desired dihydrofurans were obtained in good yields (up to 81 %) with high enantioselectivities (up to 99 % ee ) and excellent diastereoselectivities (up to &gt;99 % dr ) via one‐pot Michael addition of 1,3‐dicarbonyl derivatives to the substituted nitroolefins and a sequential I 2 ‐mediated cyclization.",10.1002/ejoc.201800575,2018-04-16,0.6124444768148105
Tetrahedron,"A three-step, highly enantioselective synthesis of (R)-2-methyl tryptophane ethyl ester: Comparison with chemical resolution",,10.1016/s0040-4039(98)00633-9,1998-05-01,0.6124348968527844
Organic Letters,Divergent Asymmetric Total Syntheses of (−)-Alloaristoteline and (+)-Aristoteline via Directed Indolization Strategies,A divergent asymmetric synthetic route to (-)-alloaristoteline and (+)-aristoteline is described. The key doubly bridged tricyclic enol triflate common intermediate prepared via enantioselective deprotonation and stepwise annulation was successfully bifurcated to complete the first completely synthetic construction of the titled natural alkaloids upon strategic implementation of the late-state directed indolization methods.,10.1021/acs.orglett.3c01224,2023-05-16,0.6123905823026916
Journal of Organic Chemistry,"Design, Synthesis, and Evaluation of 9-<scp>d</scp>-Ribityl-1,3,7-trihydro-2,6,8-purinetrione, a Potent Inhibitor of Riboflavin Synthase and Lumazine Synthase","Reduction of 5-nitro-6-D-ribitylaminouracil (9) afforded 5-amino-6-D-ribitylaminouracil (1), which reacted with ethyl chloroformate to yield 5-ethylcarbamoyl-6-D-ribitylaminouracil (12). The latter compound was cyclized to 9-D-ribityl-1,3,7-trihydropurine-2,6,8-trione (13), which was found to be a relatively potent inhibitor of both Escherichia coli riboflavin synthase (K(i) 0.61 microM) and Bacillus subtilis lumazine synthase (K(i) 46 microM). Molecular modeling of the lumazine synthase-inhibitor complex indicated the possibility for hydrogen bonding between the Lys135 epsilon-amino group of the enzyme and both the 8-keto group and the 4'-hydroxyl group of the ligand. A bisubstrate analogue of the riboflavin synthase-catalyzed reaction, 1,4-bis[1-(9-D-ribityl-1,3,7-trihydropurine-2,6,8-trionyl)]butane (18), was also synthesized using a similar route and was found to be inactive as an inhibitor of both riboflavin synthase and lumazine synthase.",10.1021/jo010706r,2001-11-09,0.612381209667166
Journal of Organic Chemistry,Synthesis of 4-Membered Carbasugars by Way of Stereoselective SmI<sub>2</sub>-Mediated Aldehyde–Alkene Cyclization,"A stereodivergent synthesis of the first examples of 4-membered carbasugars has been achieved from vitamin C by way of an efficient intramolecular SmI2-mediated aldehyde-alkene coupling. In this key step, cylobutanes with four contiguous asymmetric centers are generated with a high level of stereocontrol.",10.1021/jo400732a,2013-06-10,0.6123802540083773
Tetrahedron,A one-step route to azomethine ylides via chloroiminium salts,,10.1016/j.tetlet.2003.11.095,2003-12-11,0.6123775578459638
Organic Letters,Function-Oriented Synthesis of Pentacyclic Triterpenoids and Discovery of an <i>ent</i>-Estrane as a Natural Product-Inspired Androgen Receptor Antagonist,"While pentacyclic triterpenoids have a rich history in chemistry and biology, the challenges associated with their asymmetric synthesis contribute to the current reality that medicinal exploration in the area is largely constrained to natural product derivatization. To address this deficiency, a function-oriented synthesis of pentacyclic triterpenoids was pursued. Overall, we report a divergent synthesis of 26-norgermanicol and 26-norlupeol and we have identified a new class of androgen receptor antagonist that is ∼6× more potent than lupeol.",10.1021/acs.orglett.4c00697,2024-04-01,0.6123759660646556
Journal of Organic Chemistry,"The Power of Visual Imagery in Synthesis Planning. Stereocontrolled Approaches to CGP-60536B, a Potent Renin Inhibitor","Two strategies were developed toward the stereocontrolled synthesis of 8-aryl-3-hydroxy-4-amino-2,7-diisopropyloctanoic acids with predetermined stereogenic centers. This is a generic motif in a new class of potent inhibitors of the enzyme renin, exemplified by CGP-60536B. The synthesis relies on the utilization of L-pyroglutamic acid as chiron, and proceeds through the incorporation of required functionality by exploiting internal induction. One of the strategies shows the power of visual imagery in synthesis planning, akin to a Dali-like representation of objects that can be viewed in more than one way. Thus, the entire carbon skeleton of the target molecule is encompassed in a partially functionalized bicyclic indolizidinone precursor. In a second strategy, an intermediate common to the first approach is elaborated into an appended gamma-lactone which is alkylated through enolate chemistry and ultimately transformed into the intended target compound. X-ray crystallography was used to corroborate the structures and stereochemistries of several intermediates.",10.1021/jo011184i,2002-05-14,0.6123738311492599
Synlett,A Novel Stereocontrolled Synthesis of 3-(1′-Hydroxyethyl)-2-Azetidinone,"All articles of this category A stereoselective synthesis of 3-(1′-hydroxyethyl)-2-azetidinone, a key synthetic intermediate of carbapenem, is described.The method is based on a strategy that involves the selective imine-aldol reaction of a chiral imine with a silyl ketene acetal in the presence of a chiral boron reagent.",10.1055/s-1993-22418,1993-01-01,0.6123687851628341
Synthesis,"Total Synthesis of the Biphenomycins; II.<sup>1</sup>Synthesis of Protected (2<i>S</i>,4<i>R</i>)-4-Hydroxyornithines","All articles of this category Improved synthetic methods for the preparation of three differently protected (2 S ,4 R )-4-hydroxyornithines (10, 16, 24) have been developed which obviously can be used for the construction of the other stereoisomers. Formation of the corresponding α, β-didehydroamino acid derivatives (4, 15, 22) and their enantioselective hydrogenation are the characteristic steps of these syntheses.",10.1055/s-1991-26480,1991-01-01,0.6123544446657262
Organic Letters,Total Synthesis of the Epoxy Isoprostane Phospholipids PEIPC and PECPC,"A total synthesis of the naturally occurring hydroxy ketone PEIPC 1, a compound that plays a role in endothelial activation in atherosclerosis, has been completed via a triply convergent preparation of a protected EI derivative 13 from 3,5-diacetoxycyclopentene 7, pentane-1,5-diol, and vinyllithium, using Sharpless epoxidation and enzymatic resolution as key steps. Final coupling with lyso-PC 16 and silyl group deprotection gave PECPC 2 and PEIPC 1, which showed the same activity as natural PECPC and PEIPC. [reaction: see text]",10.1021/ol051415y,2005-07-30,0.6123418674902354
Journal of Organic Chemistry,"A Universal Strategy for Synthesis of Agropyrenol Family. Total Synthesis of Agropyrenol, Sordarial, and Heterocornol A and B","A divergent strategy for natural polyketides synthesis has been designed. This synthetic route allowed chemical alterations leading to all stereoisomers of the natural agropyrenol 1, sordarial 2, and heterocornol B 4 . Key steps involve desymmetrization of divinylcarbinol using asymmetric Sharpless epoxidation and Heck coupling of an easily available aromatic partner and prepared chiral alkene. The versatility of the synthetic method was demonstrated on the preparation of heterocornol A 3 and sordariol 5 . The absolute and relative configurations of prepared natural compounds 2 ·1/3C 6 H 12 and 4 were confirmed and assigned by single-crystal X-ray analysis.",10.1021/acs.joc.2c02092,2022-11-15,0.6123418076363373
Organic Process Research & Development,"Development of a Commercial Manufacturing Process for Sotorasib, a First-in-Class KRAS<sup>G12C</sup> Inhibitor","A commercial process to manufacture sotorasib (AMG 510), a first-in-class KRAS G12C inhibitor, is described. Development efforts focused on rendering a fit-for-purpose early-phase route into a viable long-term commercial process through the reduction of side reactions to improve yield and product quality, as well as reducing cycle times of crystallization processes by improving particle properties and filtration times. These improvements were key to ensuring clinical supply and commercial launch. The final route consists of five synthetic operations from starting material M- 1, including a telescoped two-step sequence, and a final form-setting crystallization.",10.1021/acs.oprd.2c00249,2022-10-19,0.612332703040392
European Journal of Organic Chemistry,Enantio‐ and Diastereocontrolled Total Synthesis of (+)‐Strictifolione,"Abstract A concise and practical enantioselective synthesis of (+)‐strictifolione has been achieved in high diastereomeric excess using Jacobsen's hydrolytic kinetic resolution, proline‐catalyzed sequential α‐aminoxylation and Horner–Wadsworth–Emmons olefination of aldehyde and cross olefin/ring‐closing metathesis as the key steps.",10.1002/ejoc.201001221,2010-11-04,0.6123259257106064
Organic Letters,Stereoselective Synthesis of the Butyrolactone and the Oxazoline/Furan Fragment of Leupyrrin A<sub>1</sub>,Stereoselective syntheses of the Northern and the Southern fragments 2 and 3 of leupyrrin A1 are reported. The convergent preparation of 2 is highlighted by a zirconocene-mediated one-pot cyclization-regioselective opening of an advanced diyne while the route to 3 involves a Krische allylation and a one-pot Sharpless dihydroxylation-cyclization. Comparison of the spectroscopic data with those reported for the natural product supports a relative stereochemical assignment within these heterocycles.,10.1021/ol401110x,2013-05-17,0.6123253301221638
Tetrahedron,"Enantioselective α-alkylation of piperidine via chiral perhydropyrido [2,1-b] [1,3,4]-oxadiazinone: An easy route for the synthesis of both enantiomers of coniine",,10.1016/s0040-4039(97)10438-5,1997-12-01,0.6123168083759318
Tetrahedron,"A [4+1] cyclopentannulation route to ring a aromatic, C(1)-C(11) methano-bridged steroids",,10.1016/s0040-4039(00)79764-4,1991-07-01,0.6123146422733048
Journal of Organic Chemistry,Asymmetric Synthesis of Four Isomers of 2-<i>C</i>-Trifluoromethylerythritol,"Optically active 2-C-trifluoromethylerythritols, analogues of 2-C-methylerythritol, which is a key intermediate in the biosynthesis of isoprenoid with a mevalonate-independent route, were conveniently synthesized from 1,1,1-trifluoro-2,3-epoxypropane.",10.1021/jo052282x,2006-03-21,0.6123126569726074
Organic Letters,"Stereocontrolled Divergent Total Syntheses of (+)-7-Deoxypancratistatin, (+)-7-Deoxy-<i>trans</i>-dihydronarciclasine, and (+)-Lycoricidine via Cyclic Boronic Ester-Mediated Diastereoselective Alkenylation","Stereocontrolled divergent total syntheses of Amaryllidaceae isocarbostyril alkaloids have been accomplished through the manipulation of the C(1) hydroxyl group from a common late-stage intermediate. Key features of the synthesis include (1) a cyclic boronic ester-mediated diastereoselective alkenylation for an early stage installation of the C(10b) stereocenter, (2) a chelation-controlled stereoselective syn -allylation to set the C(2) stereocenter, and (3) a rare regio- and stereoselective opening of N -Boc-aziridine followed by elimination to construct the allylic amine moiety.",10.1021/acs.orglett.5c03530,2025-10-09,0.6123032053734667
Journal of Organic Chemistry,Efficient Synthesis of Enantiopure Conduritols by Ring-Closing Metathesis,"Two short synthetic approaches to enantiopure conduritols are described starting from the chiral pool. In both cases, the cyclohexene ring is assembled via ring-closing olefin metathesis. The terminal diene precursers for the metathesis reaction are prepared either from octitols or from tartaric acids. The former route involves a new method for selective bromination of the primary positions in long-chain carbohydrate polyols. Subsequent reductive elimination with zinc then generates the diene. The latter route uses a highly diastereoselective addition of divinylzinc to tartaric dialdehydes for preparation of the dienes.",10.1021/jo0101297,2001-06-01,0.6123003707621476
Journal of Organic Chemistry,"Iron-Mediated Synthetic Routes to Unsymmetrically Substituted, Sterically Congested Benzophenones","A new synthetic route to unsymmetrically substituted benzophenones, relying upon iron-mediated reactions in all of the key steps, is described. The key buiding block, eta6-2-chloro-carbomethoxybenzene-eta5-cyclopentadienyl iron hexafluorophosphate (4), is reacted with a variety of substituted phenols, providing diaryl ether complexes (6). After hydrolysis of the ester functionalities, these complexes are subjected to Friedel-Crafts conditions. The efficiency of this intramolecular acylation reaction is very much dependent upon the substituents on the phenols. If these are appropriately chosen, xanthone complexes are isolated in fair to good yields. Regioselective ring-opening, using oxygen-nucleophiles, delivers substituted benzophenone complexes. After regioselective nucleophilic addition of cyanide ion, performed in the presence of DDQ, highly substituted benzophenones are isolated. To demonstrate the applicability of the new route, a formal synthesis of the benzophenone moiety of the protein kinase C inhibitor Balanol (3) is described.",10.1021/jo000421z,2000-08-01,0.6122996145541191
Tetrahedron,IP3 receptor-ligand. 1: Synthesis of adenophostin A,,10.1016/0040-4039(95)00916-z,1995-07-01,0.6122989949839088
Tetrahedron,IP3 Receptor-Ligand. 1: Synthesis of Adenophostin A,,10.1016/00404-0399(50)0916z-,1995-07-10,0.6122989949839088
European Journal of Organic Chemistry,Efficient Synthesis of the Pyoverdine Chromophore: Expanding the Toolbox for the Preparation of Pyoverdine Conjugates,"Abstract The pyoverdine chromophore is an important component of a family of siderophores which are secreted by the human pathogen Pseudomonas aeruginosa for iron absorption. In this study, an efficient and improved synthetic route to the chromophore structure is reported, beginning from readily available starting materials, D‐glutamic acid and L–DOPA. This strategy has not only delivered the first synthesis of the free pyoverdine D chromophore, but also offers potential access to a wide range of other pyoverdine chromophore species.",10.1002/ejoc.202400745,2024-09-20,0.6122937971091468
Organic Process Research & Development,Green Chemical Synthesis of 2-Benzenesulfonyl-pyridine and Related Derivatives,"A practical synthesis of 2-benzenesulfonylpyridine, 1, is described which is a key starting material for the manufacture of an investigational new drug candidate at Eli Lilly and Company. An optimized green chemical process was developed which features a novel tandem S N Ar/oxidation under mild conditions to produce the target sulfone, 1, in 86% yield and>99% purity. In addition, this novel, environmentally friendly methodology was found to be general for the synthesis of substituted aromatic pyridyl sulfides and sulfones.",10.1021/op700060e,2007-07-28,0.6122866659642207
Synthesis,First Synthesis of Benzopyridoiodolium Salts and Twofold Buchwald-Hartwig Amination for the Total Synthesis of Quindoline,The first synthesis of cyclic benzopyridoiodolium salts is described. These hypervalent iodine intermediates are used in an efficient strategy for the construction of the δ-carboline core. This novel approach involves a twofold palladium-catalyzed Buchwald-Hartwig reaction between these unprecedented reagents and a primary amine. Our methodology successfully provides the expected N-substituted δ-carboline core and is efficiently applied in the total synthesis of quindoline.,10.1055/s-0031-1289652,2011-12-22,0.6122832430250806
Organic Process Research & Development,"Development of a Scalable Synthetic Process for DG-051B, A First-in-Class Inhibitior of LTA4H","DG-051B is a first-in-class small molecule inhibitor of leukotriene A4 hydrolase (LTA4H), currently in Phase II clinical development for the prevention of heart attack. Process optimization led from a linear seven-step synthetic procedure to a convergent four-step manufacturing sequence that has been used to manufacture at 100-kg scale. The entire process can be telescoped due to high conversion reactions, low impurity levels, efficient separations, and a very effective final purification. Two key aspects of the process are: (a) bypassing the isolation of a reactive electrophile by using its aqueous-washed reaction mixture directly into a coupling reaction with a phenoxide nucleophile and (b) modulating the properties of the final product solutions for optimal extraction, purification, and crystallization.",10.1021/op900231j,2009-11-02,0.6122521806034359
Tetrahedron,An angular hydroxylation route to taxanes: Facile access to the bridged AB ring system of taxol,,10.1016/s0040-4039(97)00583-2,1997-05-01,0.6122487384948868
Synthesis,"An Access to Chiral β-Benzyl-γ-butyrolactones and Its Application to the Synthesis of Enantiopure (+)-Secoisolariciresinol, (-)-Secoisolariciresinol, and (-)-Enterolactone","Both enantiomers of secoisolariciresinol and enantiopure (-)-enterolactone were synthesized through a highly stereoselective convergent synthesis. An Evans diastereoselective alkylation followed by a substrate-induced diastereoselective alpha-alkylation of the newly formed optically active beta-benzyl-gamma-butyrolactone gave the beta-beta' linkage of the target skeleton. The (S,S)- and (R,R)-enantiomers of secoisolariciresinol and (-)-enterolactone were obtained in 12-14% (11 steps) and 20% (7 steps) overall yield, respectively.",10.1055/s-0030-1259982,2011-04-01,0.6122396295744343
Organic Letters,Enantioselective Total Synthesis of Beraprost Using Organocatalyst,A convergent and enantioselective total synthesis of the most active isomer of beraprost was achieved in 17 pots. A unique tricyclic core in beraprost was synthesized efficiently by utilizing the asymmetric organocatalyst-mediated formal [3 + 2] cycloaddition reaction of succinaldehyde with nitroalkene as a key step. The synthesis of the optically active Horner-Wadsworth-Emmons reagent for the construction of the ω-side chain was also established by means of the enantioselective Michael reaction of crotonaldehyde with nitromethane catalyzed by the organocatalyst developed by our group.,10.1021/acs.orglett.7b00134,2017-02-23,0.6122294799293723
Journal of Organic Chemistry,"Stereoselective Synthesis and Conformational Study of Novel 2′,3′-Didehydro-2′,3′-dideoxy-4′-selenonucleosides","Stereoselective synthesis of novel 2',3'-didehydro-2',3'-dideoxy-4'-selenonucleosides (4'-seleno-d4Ns) 4a- c was accomplished via 4'-selenoribofuranosyl pyrimidines 11a- c, as key intermediates. 4'-Selenoribofuranosyl pyrimidines 11a- c were efficiently synthesized from d-ribose or d-gulonic gamma-lactone using a Pummerer-type condensation as a key step. Introduction of 2',3'-double bond was achieved by treating cyclic 2',3'-thiocarbonate with 1,3-dimethyl-2-phenyl-1,3,2-diazaphospholidine.",10.1021/jo8003277,2008-05-03,0.6122200089411145
European Journal of Organic Chemistry,"Pyrrolo[2,1‐ <i>f</i> ][1,2,4]triazin‐4‐amine: Synthesis, <i>C</i> 7‐Functionalization, and NH <sub>2</sub> ‐Derivatization via Buchwald–Hartwig‐Type Coupling","An optimized gram‐scale synthetic route to pyrrolo[2,1‐ f ][1,2,4]triazin‐4‐amine is reported, affording an overall yield of 85%. Furthermore, regioselective C 7‐functionalization is achieved via both organometallic and direct strategies, whereas NH 2 ‐derivatization proceeds through Buchwald–Hartwig‐type coupling, providing derivatives in isolated yields ranging from 8% to &gt;99%. These advancements enhance synthetic accessibility and facilitate efficient structural diversification of this significant N ‐heterocycle.",10.1002/ejoc.202500512,2025-10-24,0.6122190125308602
Tetrahedron,Convergent synthesis of (R)-silodosin via decarboxylative cross-coupling,,10.1016/j.tetlet.2021.153290,2021-07-24,0.6122183401783449
Tetrahedron,"A facile and practical synthesis of the derivatives of 1-O-acetyl-2-deoxy-2-hydroxymethyl-D-erythrooxetanose, a key sugar moiety for the synthesis of oxetanosyl-N-glycoside",,10.1016/s0040-4039(00)94349-1,1990-01-01,0.6122078484882952
Organic Process Research & Development,An Efficient Enantiopure Synthesis of a Pivotal Precursor to Substance P Antagonists<sup>1</sup>,"Many substance P antagonists have a core structure based on the quinuclidine skeleton. Manufacture of these drug antagonists proceeds through the advanced intermediate (2 S,3 S )- cis -2-benzhydryl-3-aminoquinuclidine 1, and all previous syntheses of 2 S,3 S - 1 proceed through quinuclidinone 2 . The synthesis described herein provides a 40% improved synthetic yield of (2 S,3 S )- 1 from quinuclidinone 2, when compared to all previously reported syntheses. The key process improvements originate from: (1) dynamic kinetic resolution of ketone rac - 4, producing ketone (2 S )- 4 and (2) the subsequent reductive amination of ketone (2 S )- 4 without epimerization. The former dynamic kinetic resolution, the first demonstrated for this ketone (quinuclidinone) architecture, uses inexpensive (natural) l -tartaric acid to provide ketone (2 S )- 4 in high yield (90%) and enantiopurity (95% ee). The latter demonstrates the first use of Ti(O i Pr) 4 /Pt-C/H 2 for reductive amination and is especially noteworthy for its ability to preserve the α-labile C2 stereocenter of ketone (2 S )- 4 . The new reductive amination method is general in nature and should find broad applicability.",10.1021/op050213e,2005-12-23,0.6122059776910901
Chemical Science,Concise total synthesis of (+)-bionectins A and C,"The concise and efficient total synthesis of (+)-bionectins A and C is described. Our approach to these natural products features a new and scalable method for erythro-β-hydroxytryptophan amino acid synthesis, an intramolecular Friedel–Crafts reaction of a silyl-tethered indole, and a new mercaptan reagent for epipolythiodiketopiperazine (ETP) synthesis that can be unravelled under very mild conditions. In evaluating the impact of C12-hydroxylation, we have identified a unique need for an intramolecular variant of our Friedel–Crafts indolylation chemistry. Several key discoveries including the first example of permanganate-mediated stereoinvertive hydroxylation of the α-stereocenters of diketopiperazines as well as the first example of a direct triketopiperazine synthesis from a parent cyclo-dipeptide are discussed. Finally, the synthesis of (+)-bionectin A and its unambiguous structural assignment through X-ray analysis provides motivation for the reevaluation of its original characterization data and assignment.",10.1039/c3sc51150b,2013-01-01,0.6122036009012782
Organic Letters,Total Synthesis of the Oxopolyene Macrolide (−)-Marinisporolide C,"The first total synthesis of (-)-marinisporolide C was performed in 25 steps (longest linear sequence) and an overall yield of 1%. Due to the high degree of convergence and robustness, the C9-C35 fragment that corresponds to the polyol portion was obtained in gram quantity. Highlights of this synthesis include five highly stereoselective aldol reactions responsible for the construction of five C-C bonds and six stereogenic centers. Additionally, a very efficient Julia-Kocieński reaction was used to install a C22-C23 double bond, and the macrocyclic ring was closed using an intramolecular Horner-Wadsworth-Emmons olefination.",10.1021/acs.orglett.5b03352,2015-12-09,0.6122016726187138
Tetrahedron,An improved synthesis of the C15–C28 fragment of laulimalide,,10.1016/s0040-4039(01)02120-7,2002-01-01,0.6121957034510104
Tetrahedron,An improved synthesis of hemichrysophaentin-AB fragment of chrysophaentin A,,10.1016/j.tetlet.2020.151856,2020-03-18,0.6121957034510104
Organic Letters,Quaterpyrroles as Building Blocks for the Synthesis of Expanded Porphyrins,"A new family of quaterpyrroles and their application as building blocks for the synthesis of macrocycles is reported. The preparation of these quaterpyrroles consisted of two synthetic steps: bromination of 2,2'-bipyrroles bearing two electron-withdrawing groups followed by Suzuki coupling with 1-(tert-butoxycarbonyl)pyrrole-2-boronic acid. The resulting quaterpyrroles have been used to prepare an octaphyrin and a substituted cyclo[8]pyrrole. Additionally, the synthesis of a new macrocycle containing the quaterpyrrole and 2,5-di(1H-pyrrol-2-yl)thiophene moieties is presented.",10.1021/acs.orglett.5b00767,2015-04-22,0.6121954082558118
Angewandte Chemie International Edition,Total Synthesis of Theopederin D,"The transformation is complete! The total synthesis of theopederin D (see structure), a potent cytotoxin, has been achieved through oxidative cleavage of a carbon–carbon bond. Other key transformations include an acid-mediated functionalization of a tetrahydrofuranol, a syn-selective glycal epoxide ring-opening, and an asymmetric aldehyde/acid chloride condensation.",10.1002/anie.200802548,2008-09-03,0.6121919696093646
Journal of the American Chemical Society,Total Synthesis of (±) Maoecrystal V,"A concise first total synthesis of (±) maoecrystal V (1) is reported. The synthesis features a Wessely oxidative dearomatization of a phenol, an intramolecular Diels-Alder reaction, and a Rh-catalyzed O-H bond insertion as key steps.",10.1021/ja108907x,2010-11-04,0.6121893399866187
Journal of Organic Chemistry,Formal Total Synthesis of (−)-Jiadifenolide and Synthetic Studies toward <i>seco</i>-Prezizaane-Type Sesquiterpenes,"Synthetic studies toward highly oxygenated seco-prezizaane sesquiterpenes are reported, which culminated in a formal total synthesis of the neurotrophic agent (-)-jiadifenolide. For the construction of the tricyclic core structure, an unusual intramolecular and diastereoselective Nozaki-Hiyama-Kishi reaction involving a ketone as electrophilic coupling partner was developed. In addition, synthetic approaches toward the related natural product (2R)-hydroxy-norneomajucin, featuring a Mn-mediated radical cyclization for the tricycle assembly and a regioselective OH-directed C-H activation are presented.",10.1021/acs.joc.6b02039,2016-10-14,0.6121821911012802
Journal of the American Chemical Society,Total Synthesis of Piericidin A1. Application of a Modified Negishi Carboalumination-Nickel-Catalyzed Cross-Coupling,"A total synthesis of the mitochondrial complex I inhibitor piericidin A1 is described. It features a unique strategy for the key disconnection, highlighting a modified Negishi carboalumination/Ni-catalyzed cross-coupling on a polyenyne precursor.",10.1021/ja809542r,2009-01-12,0.6121773843630659
Synthesis,Three-Component Condensation for the Construction of Novel Spirooxindoles,"A new route for the synthesis of novel spirooxindoles from isocyanides, dialkyl acetylenedicarboxylates, and N-substituted isatylidene derivatives through [3+2] cycloaddition has been developed. This method has several advantages, such as high regioselectivity, high yields, readily available starting materials, and one-pot operations. The synthetic alkyne-containing spirooxindoles could also be used in the selective synthesis of triazole-containing­ spirocyclic compounds using a copper azide–alkyne cycloaddition­ (CuAAC) reaction.",10.1055/s-0032-1316836,2012-12-21,0.6121696132081673
Organic Letters,An Asymmetric Synthesis of <scp>l</scp>-Pyrrolysine,An efficient asymmetric synthesis of the 22nd amino acid L-pyrrolysine has been accomplished. The key stereogenic centers were installed by an asymmetric conjugate addition reaction. A Staudinger/aza-Wittig cyclization was used to form the acid-sensitive pyrroline ring. Pyrrolysine was synthesized in 13 steps in 20% overall yield.,10.1021/ol300045c,2012-03-06,0.6121621275339938
Synlett,"Synthesis of (3<i>S</i>)-Hydroxyandrosta-5,7-diene-17-ones via Intramolecular Cobalt-Mediated [2+2+2] Cycloaddition","A new method for the synthesis of lumisterin-type steroids following the D→ABCD approach is reported. A key step is the cobalt-induced cyclization of a cyclopentanoid enediyne, which was prepared via thioalkylation of the zinc enolate of a 2,3-substituted cyclopentanone with α-chlorosulfides.",10.1055/s-2006-939064,2006-03-14,0.6121574008399551
Organic Letters,Stereoselective Synthesis of Methyl Monate C,"[Structure: see text] The stereoselective synthesis of methyl monate C 2 is described using as a key step an ene-intramolecular modified Sakurai cyclization (IMSC) reaction to prepare tetrahydropyran 5. An asymmetric allylic alkylation, followed by a cross-metathesis, enables the insertion of the right-hand side chain.",10.1021/ol0625785,2006-11-18,0.6121564738658878
Journal of Organic Chemistry,"An Improved Method for the Synthesis of Dissymmetric N,N‘-Disubstituted Imidazole-4,5-dicarboxamides","Symmetrically and dissymmetrically disubstituted imidazole-4,5-dicarboxamides (I45DCs) have diverse bioactivities and therefore represent useful small molecules for lead structure identification in drug discovery. For this reason, an improved synthesis was developed as a first step in the preparation of greater numbers of analogues. The method involves the transformation of imidazole-4,5-dicarboxylic acid into dissymmetrically disubstituted I45DCs in four steps and in a minimum yield of 51%. This reflects an overall reduction of one synthetic step and a greater than 30% improvement in yield over the known method.",10.1021/jo025536c,2002-09-04,0.6121498518704468
Organic Process Research & Development,"Synthesis of Filibuvir. Part II. Second-Generation Synthesis of a 6,6-Disubstituted 2<i>H</i>-Pyranone via Dieckmann Cyclization of a β-Acetoxy Ester","This paper describes an improved sequence for the conversion of an oxazolidinone ( 3 ) to a β-keto lactone ( 5 ). The primary drivers behind this change were the modest and variable yields observed in the intramolecular cyclization to generate the β-keto lactone. Changing the cyclization substrate from oxazolidinone to alkyl ester offered a significantly improved cyclization, as well as improvements in the alkyne hydrogenation. Selection of the optimal substrates for methanolysis and intermediate salt formation are also described.",10.1021/op400236r,2013-11-26,0.612144710549671
Synlett,A New Concise Synthesis of Methylenomycin B,"All articles of this category Methylenomycin B ( 1 ; 2,3-dimethyl-5-methylene-2-cyclopenten-1-one) has been synthesized from diethyl methylphosphonate ( 2 ) in four steps in overall 24% yield. The key steps in this synthesis involve the intramolecular carbenoid cyclization of diethyl 1-diazo-3,4-dimethyl-2-oxo-3-pentenylphosphonate ( 5 ) and the Horner-Emmons reaction of diethyl 3,4-dimethyl-2-oxo-3-cyclopentenylphosphonate ( 6 ) with formaldehyde.",10.1055/s-1991-20803,1991-01-01,0.6121447085280051
Tetrahedron,Asymmetric synthesis of (R)-reticuline. A new strategy for the asymmetric synthesis of isoquinolines via enantioselective epoxidation or dihydroxylation,,10.1016/s0040-4039(00)97306-4,1990-01-01,0.6121270908694671
Journal of Organic Chemistry,"Enantio- and Diastereoselective Total Synthesis of EI-1941−1, −2, and −3, Inhibitors of Interleukin-1β Converting Enzyme, and Biological Properties of Their Derivatives","[reaction: see text] The first asymmetric total synthesis of EI-1941-1, -2, and -3, inhibitors of the interleukin-1beta converting enzyme (ICE), has been accomplished, starting from a chiral epoxy iodoquinone 11, a key intermediate in our total synthesis of epoxyquinols A and B. Despite a failure to synthesize the inhibitors by our postulated biosynthetic route, we were able to diastereoselectively synthesize them via an intramolecular carboxypalladation with the key steps being a 6-endo cyclization mode followed by beta-hydride elimination. The investigation of the biological properties of EI-1941-1, -2, and -3 and their derivatives disclosed them to be potent and effective ICE inhibitors with less cytotoxicity than EI-1941-1 and -2 in a cultured cell system.",10.1021/jo0516436,2005-11-01,0.6121255400713908
Journal of Organic Chemistry,Tetrachloromaxamycins: Divergent Total Synthesis and Initial Assessments,"Divergent total syntheses of binding pocket and peripherally modified tetrachlorovancomycins, a non-native synthetic glycopeptide, and their evaluation are disclosed. Central to the approach is the synthesis of a single late-stage intermediate that bears a residue 4 thioamide ([Ψ[C(═S)NH]Tpg 4 ]tetrachlorovancomycin ( 3 ), LLS 15 steps, 14% overall) as a precursor to either of two key pocket modifications and their pairing with any combination of two peripheral modifications conducted without protecting groups. A stereochemical simplification achieved by the addition of two aryl chlorides removes two synthetically challenging atropisomer centers in native glycopeptides and streamlines the synthesis. Key features include in a convergent epimerization-free thioacylation of the AB ring system amine with an N -thioacylbenzotriazolyl DE tetrapeptide (85%) followed by simultaneous room-temperature S N Ar macrocyclizations of the CD and DE ring systems (96%). The approach provided 3 from which [Ψ[C(═N)NH]Tpg 4 ]tetrachlorovancomycin ( 4 ) and [Ψ(CH 2 NH)Tpg 4 ]tetrachlorovancomycin ( 5 ) were prepared in a single-step and bear binding pocket modifications that convey dual d -Ala- d -Ala/ d -Lac ligand binding to overcome vancomycin resistance. The newest maxamycin members are disclosed, bearing two additional peripheral modifications that introduce two independent synergistic MOAs that do not rely on native ligand binding for activity. Ligand binding properties of pocket-modified tetrachlorovancomycins 3 – 5, antibacterial activity of a key compound series, and PK assessments of two tetrachloromaxamycins are reported.",10.1021/acs.joc.4c01927,2024-08-22,0.6121205834835131
Tetrahedron,"Stereocontrolled reduction of an oxazepinohexahydroindolo[2,3- a ]quinolizine derivative: asymmetric total synthesis of (+)-tacamonine",,10.1016/s0040-4039(01)01488-5,2001-10-01,0.6121165742581558
Tetrahedron,"The first total synthesis of lamellarin α 20-sulfate, a selective inhibitor of HIV-1 integrase",,10.1016/j.tetlet.2006.03.121,2006-04-13,0.6121113133193814
European Journal of Organic Chemistry,Synthetic Approaches to Hydroazulenes and Guaianes through [4 + 3] Cycloadditions of Oxyallyl Intermediates,"Abstract Building blocks for syntheses of guaiane and secoguaiane sesquiterpenoids were prepared by the title reaction. 4‐(3‐Methylfuran‐2‐yl)butan‐2‐one ( 1 ) was obtained in five steps from methyl 3‐methylfuran‐2‐carboxylate ( 4 ), and treatment of 1 with pentachloroacetone and sodium 2,2,3,3‐tetrafluoropropoxide in 2,2,3,3‐tetrafluoropropan‐1‐ol produced a [4 + 3] cycloadduct that was dechlorinated without prior isolation to give the oxabicyclic diketone 2 in a low yield. A better route to diketone 2 was via the oxabicycle 10b , prepared in a high yield from 2‐(but‐3‐en‐1‐yl)‐3‐methylfuran ( 9 ) and pentachloroacetone, followed by dechlorination. Treatment of 2 with dilute methanolic potassium hydroxide resulted in the cleavage of the oxa bridge, with formation of 3,8‐dimethylazulen‐4‐ol ( 11 ). Catalytic hydrogenation of 2 afforded the saturated oxabicyclic diketone 14 , intramolecular aldol condensation of which gave the tricycle 15 . The oxa bridge of the oxatricyclic enone 15 was cleaved by hydrogenolysis in the presence of palladium/carbon catalyst to give the 6‐hydroxydecahydroazulen‐4‐one 16 . Treatment of isobutyl trichloromethyl ketone ( 20 ) with furan 9 and sodium trifluoroethoxide in trifluoroethanol eventually gave the 2‐chlorooxabicycle 22 . This solvolysis product was dechlorinated to furnish the oxabicyclic trifluoroethoxy ketone 24 as a single product that was subjected to the sequence of transformations used for 10b . X‐ray structure analysis of the resulting saturated diketone 26 established the endo configuration of the isopropyl group. Finally, aldol cyclization of 26 furnished the guaiane derivative 27 . (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2006)",10.1002/ejoc.200500777,2006-03-17,0.6120887186007691
European Journal of Organic Chemistry,Stereoselective Synthesis of Aza Analogues of Isoaltholactone and Goniothalesdiol – New Applications of the Heck–Matsuda Reaction,"Abstract The stereoselective synthesis of nitrogen analogues of biologically active isoaltholactone and goniothalesdiol are described. The successful strategy employed a Heck–Matsuda reaction between a chiral endocyclic enecarbamate bearing an ester functionality and arenediazonium tetrafluoroborates in a divergent approach at an early stage of the synthesis. Several aspects related to this critical arylation reaction are discussed to highlight structural features that affect the outcome of the arylation process. The synthesis of (–)‐aza‐isoaltholactone 6 was successfully accomplished in nine steps from the starting enecarbamate. We also performed the synthesis of the new fully substituted pyrrolidine (–)‐(2 R ,3 R ,4 S ,5 S )‐1‐( tert ‐butoxycarbonyl)‐3,4‐dihydroxy‐5‐phenylpyrrolidin‐2‐ylacrylic acid 28 , which is a potential advanced intermediate in the route to aza‐altholactone. Moreover, the synthesis of a new nitrogen analogue of goniothalesdiol (+)‐ 33 was accomplished from the protected dihydroxypyrrolidine (–)‐ 27 , obtained from an attempted synthesis of aza‐altholactone.",10.1002/ejoc.201100886,2011-09-15,0.6120832648148358
Synthesis,Towards the Synthesis of the Cornexistins,A concise synthetic route to the carbocyclic core of the cornexistins is reported. The route is highlighted by a Diels-Alder cycloaddition/oxidative cleavage strategy to generate the central highly functionalized nine-member ring. A silyl-tethered ring-closing metathesis strategy is utilized to control trisubstituted alkene geometry.,10.1055/s-2007-983769,2007-07-01,0.6120817108322325
Angewandte Chemie International Edition,Palladium‐Catalyzed Enantioselective Domino Reaction for the Efficient Synthesis of Vitamin E,A new route to vitamin E: The palladium-catalyzed enantioselective domino reaction of the unsaturated phenol derivative 1 with acrylate provides efficient access to the chiral chroman 2 with 96 % ee and in 84 % yield (see scheme). Intermediate 2 can then be converted into vitamin E in a few steps.,10.1002/anie.200461629,2004-11-26,0.6120792759658791
Angewandte Chemie International Edition,Total Synthesis of the <i>Euphorbia</i> Diterpenoid Pepluacetal,"Abstract The first total synthesis of the Euphorbia diterpenoid pepluacetal is disclosed in both racemic and chiral fashions. The synthesis strategically relies on a photo‐induced Wolff rearrangement/lactonization cascade (WRLC) reaction to access the cyclobutane moiety, a ring‐closing metathesis/cyclopropanation sequence to rapidly forge the 7–3 bicyclic system, and a late‐stage Rh‐catalyzed transannular carbenoid insertion to C(sp 3 )−H bond followed by a Baeyer–Villiger oxidation and ring‐opening manipulations to install the side chain. The synthetic route demonstrates excellent stereochemical control on the non‐classical concave‐face bond formation, remote traceless stereochemical relay and high scalability to provide 20 mg of (+)‐pepluacetal.",10.1002/anie.202400943,2024-03-21,0.6120754901581921
Journal of the American Chemical Society,"Asymmetric Synthesis of (2<i>S</i>,3<i>R</i>)-Capreomycidine and the Total Synthesis of Capreomycin IB","A 27 step total synthesis of the tuberculostatic macrocyclic peptide antibiotic capreomycin IB has been accomplished. The synthesis features the use of an enolate-aldimine condensation between a chiral glycine aluminum enolate and the benzyl imine of 3-tert-butyldimethylsiloxy-propanal as a means of preparing the cyclic guanidine amino acid (2S,3R)-capreomycidine. Additionally, a Hofmann rearrangement was exacted on a late-stage pentapeptide in order to transform an asparagine residue into a diaminopropanoic acid residue.",10.1021/ja0351241,2003-06-20,0.6120632153694133
Organic Letters,Diastereoselective Total Synthesis of Salvileucalin C,"A concise and efficient approach for the diastereoselective total synthesis of salvileucalin C, as well as their biosynthetically related diterpenoids salvileucalin D, salvipuberulin, isosalvipuberulin, and dugesin B, has been reported for the first time. The key features of the strategy are based on a Beckwith-Dowd ring expansion, a tandem diastereoselective Stille coupling/debromination/desilylation/lactonization reaction, and a photoinduced electrocyclic ring contraction.",10.1021/ol501423t,2014-06-04,0.6120527110514953
Tetrahedron,Synthetic studies on glycophosphatidylinositol anchor: a highly efficient synthesis of glycobiosyl phosphatidylinositol through H-phosphonate approach,,10.1016/s0040-4039(00)71229-9,1991-01-01,0.6120502546416675
Journal of the American Chemical Society,A Highly Convergent Total Synthesis of Leustroducsin B,Leustroducsin B exhibits a large variety of biological activities and unique structural features. An efficient and highly convergent total synthesis of Leustroducsin B was achieved in 17 longest linear and 39 total steps by disconnecting the molecule into three fragments having similar levels of complexity. These pieces were connected via a highly efficient chelate-controlled addition of a vinyl zincate to an α-hydroxy ketone and a silicon-mediated cross-coupling. The stereochemistry of the central and western fragments was set catalytically in high yields and excellent de by a zinc-ProPhenol-catalyzed aldol reaction and a palladium-catalyzed asymmetric allylic alkylation.,10.1021/jacs.5b07438,2015-08-27,0.6120445360510919
Journal of Organic Chemistry,"Progress toward the Total Synthesis of Lymphostins: Preparation of a Functionalized Tetrahydropyrrolo[4,3,2-<i>de</i>]quinoline and Unusual Oxidative Dimerization","The lymphostins are a family of closely related pyrrolo[4,3,2- de ]quinoline natural products produced by Streptomyces and Salinispora actinobacteria. Neolymphostin A was recently shown to strongly inhibit phosphoinositide 3-kinase (PI3K) and the mammalian target of rapamycin (mTOR) in a covalent manner via conjugation to a catalytic lysine residue in the ATP-binding pocket of the enzymes, making this metabolite the first reported covalent kinase inhibitor from a bacterium. A flexible and efficient synthetic route toward these alkaloids would allow for improvements in their solubility, stability, and selectivity and help to deliver a viable drug candidate. We have since established a short synthesis to methyl 8-bromo-1,3,4,5-tetrahydropyrrolo[4,3,2- de ]quinoline-4-carboxylate via a conjugate addition/intramolecular Ullman reaction sequence. However, attempts to oxidize this intermediate to the pyrrolo[4,3,2- de ]quinoline characteristic of the lymphostins resulted in formation of either a 2-oxo-1,2-dihydropyrrolo[4,3,2- de ]quinoline or an unusual N, C -linked tetrahydropyrroloquinoline-pyrroloquinoline heterodimer. We expect that key modifications to the tetrahydropyrroloquinoline intermediate prior to oxidation should prevent these side reactions and pave the way for the completion of the synthesis.",10.1021/acs.joc.9b01041,2019-06-19,0.6120388266370134
Journal of Organic Chemistry,"Facile Synthesis of Structurally Diverse 3,3′-Disubstituted 1,1′-Binaphthyl-2,2′-diamines in Optically Pure Forms","A new synthetic route to 3,3'-dihalo BINAMs based on the direct halogenation of H8-BINAM and subsequent rearomatization to the binaphthyl core has been developed. The combination of this new procedure and Pd-catalyzed coupling reactions enabled us to synthesize various 3,3'-disubstituted BINAMs in only three steps starting from H8-BINAM.",10.1021/jo8011368,2008-08-15,0.6120363044151889
Angewandte Chemie International Edition,Total Synthesis of Isorosthin L and Isoadenolin I,"Total syntheses of two Isodon diterpenes, isorosthin L and isoadenolin I, are reported. The synthetic strategy features a quick assembly of two simple building blocks through a diastereoselective intermolecular aldol reaction and a subsequent radical cyclization for efficient construction of a rather complex advanced intermediate bearing a quaternary stereocenter present in all Isodon diterpenes. Oxidative cleavage of the C-C bond in the cyclopentane enabled the conversion to a lactone moiety which is desired for the construction of the molecular skeleton through reductive coupling with an aldehyde carbonyl group.",10.1002/anie.202114489,2021-11-13,0.612035300882011
Journal of Organic Chemistry,Tandem [4 + 2]/[3 + 2] Cycloadditions of Nitroalkenes. 13. The Synthesis of (−)-Detoxinine,"(−)-Detoxinine, an unusual, highly-functionalized amino acid, is the core residue of many components that comprise the detoxin complex. The synthesis of (−)-detoxinine was accomplished in 10 steps and 13.4% overall yield from commercially available dichlorodiisopropylsilane. The key step is an asymmetric tandem inter [4 + 2]/intra [3 + 2] cycloaddition between silyoxynitroalkene 17 and chiral vinyl ether (−)- 24, illustrating the application of a temporary silicon tether in the tandem nitroalkene cycloaddition process.",10.1021/jo962306n,1997-03-01,0.612031731565863
Synlett,"Pd-Catalyzed Cyclization Approach to Chiral A-Ring Synthon for 1α,2β,25-Trihydroxyvitamin D<sub>3</sub>","All articles of this category Synthesis of a chiral A-ring synthon for 1α, 2β, 25-trihydroxyvitamin D 3 starting from d -mannitol by using palladium-catalyzed cyclization of the ( Z )-vinyl iodide is described.",10.1055/s-1993-22338,1993-01-01,0.6120295372983908
Tetrahedron,"A new synthetic approach to the benzazole ring system. Synthesis and electrocyclic ring closure of dialkenyl and alkenyl-aryl substituted pyrroles, imidazoles and oxazoles",,10.1016/s0040-4039(00)84479-2,1986-01-01,0.6120247195465774
Tetrahedron,"Synthesis of a novel 4,6′-epoxymorphinan derivative and a highly strained novel conjugated ketone",,10.1016/j.tetlet.2007.07.194,2007-08-03,0.6120122884865264
Tetrahedron,"VOSO 4 catalyzed highly efficient synthesis of benzimidazoles, benzothiazoles, and quinoxalines",,10.1016/j.tetlet.2016.06.074,2016-06-27,0.6119990617790457
Tetrahedron,"Highly efficient synthesis of 3-pyrrolyl-indolinones and pyrrolyl-indeno[1,2-b]quinoxalines catalyzed by heteropolyacids",,10.1016/j.tetlet.2008.07.015,2008-07-07,0.6119990617790457
Journal of the American Chemical Society,Convergent Total Synthesis of (−)-Calidoustene,"The first total synthesis of the sesterterpenoid (−)-calidoustene has been accomplished, featuring a stereoselective Michael/aldol cascade to construct the trans -hydrindane backbone, a tandem Pummerer/Sakurai cyclization to establish the bicyclo[3.2.1]octane framework, a metallaphotoredox enone coupling followed by MHAT-initiated cyclization to forge the congested central C-ring, and late-stage functionalization via Cu-catalyzed desaturation and diimide reduction.",10.1021/jacs.5c03983,2025-04-29,0.6119963504533115
Angewandte Chemie International Edition,Synthesis of a Bicyclobutane Fatty Acid Identified from the Cyanobacterium <i>Anabaena</i> PCC 7120,"By design: a carbanion-mediated cyclization reaction cascade serves as the key final step in the total synthesis of a novel oxylipin, which features a strained bicyclo[1.1.0]butane conjugated to a labile vinyl epoxide.",10.1002/anie.201104366,2011-09-07,0.611996122255081
Angewandte Chemie International Edition,Total Syntheses of Crinipellins Enabled by Cobalt‐Mediated and Palladium‐Catalyzed Intramolecular Pauson–Khand Reactions,"Efficient total syntheses of the naturally occurring, potent antibiotic compounds (-)-crinipellin A and (-)-crinipellin B are described. The key advanced intermediate, a fully functionalized tetraquinane core, was constructed by a novel thiourea/palladium-catalyzed Pauson-Khand reaction. This intermediate can serve as a common intermediate for the collective total synthesis of other members of the crinipellin family.",10.1002/anie.201805143,2018-05-25,0.6119941667382618
Tetrahedron,A short and efficient synthesis of (−)-methyl 8-epi-nonactate,,10.1016/0040-4039(93)85020-w,1993-03-01,0.6119794538444833
Synthesis,"Synthesis of a Chiral and Fluorescent Sugar-Based Macrocycle by 1,3-Dipolar Cycloaddition","An efficient and modular synthesis of a chiral, amphiphilic, and fluorescent macrocycle is described. A bis-acetylene was prepared by coupling the amino group of a sugar delta-amino acid with a glutamic acid propargylic amide derivative, followed by coupling of the sugar delta-amino acid carboxy group with a glutamic acid propiolyl amide. The bis-acetylene was reacted with 9,10-bis(azidomethyl)anthracene under Cu(I) catalysis to afford the target fluorescent macrocycle.",10.1055/s-2006-942503,2006-07-19,0.6119790204948352
Angewandte Chemie International Edition,Total Synthesis of (±)‐FR66979,"An unusual fragmentation of aziridine 1, triggered by a preliminary homo-Brook transposition is the key step in the total synthesis of the racemate of the antitumor agent FR66979 (2).",10.1002/anie.200290017,2002-12-12,0.6119762252380476
Organic Letters,"(−)-(2<i>S</i>,3<i>R</i>,<i>Z</i>)-Nakinadine A: First Asymmetric Synthesis and Absolute Configuration Assignment","Mannich-type reaction of methyl phenylacetate with the N-tert-butylsulfinyl imine derived from (R)-tert-butylsulfinamide and (Z)-14-(pyridin-3'-yl)tetradec-11-enal has been used as the key step in the first asymmetric synthesis of (-)-nakinadine A. Both the 2,3-syn- and 2,3-anti-diastereoisomers were prepared; comparison of spectroscopic and specific rotation data facilitated assignment of the absolute (2S,3R,Z)-configuration within the natural product. (-)-(2S,3R,Z)-Nakinadine A was prepared in 10 steps from 11-bromoundecan-1-ol, in 10% overall yield, 97:3 dr [(Z):(E) ratio], and >98% ee.",10.1021/ol500096r,2014-02-25,0.611973495923778
Tetrahedron,"An efficient enantioselective synthesis of 1α,25-dihydroxyvitamin D3 A-ring synthon",,10.1016/s0040-4039(00)00170-2,2000-04-01,0.6119712759397475
Tetrahedron,"Synthesis of (R)-3,4-dihydro-2H-pyran-2-carboxaldehyde: application to the synthesis of potent adenosine A2A and A3 receptor agonist",,10.1016/j.tetlet.2009.03.148,2009-03-27,0.611970497199392
Journal of the American Chemical Society,Enantioselective Total Synthesis of (+)-Euphorikanin A,"We disclose the first total synthesis of (+)-euphorikanin A, an ingenane-derived natural product featuring an unprecedented 5/6/7/3-fused tetracyclic skeleton. Key to the approach is a SmI 2 -mediated ketyl–enoate reaction that leads to the formation of two rings in a single step. The polarity-reversed cyclization proceeds in excellent yield and high diastereoselectivity. Access to ring B is effected late in the synthesis by implementation of a number of chemoselective transformations, including in situ generation of a vinyl lithium species and subsequent intramolecular attack onto an α-ketolactone.",10.1021/jacs.1c04210,2021-05-27,0.6119693849206663
Tetrahedron,"Eudistomidin-A, a novel calmodulin antagonist from the okinawan tunicate",,10.1016/s0040-4039(00)84213-6,1986-01-01,0.6119615102198636
Journal of the American Chemical Society,Stereocontrolled Total Synthesis of (−)-Vincamajinine and (−)-11-Methoxy-17-epivincamajine,"The first total syntheses of (-)-vincamajinine (5) (from Na-methyl-d-tryptophan methyl ester) and (-)-11-methoxy-17-epivincamajine (6) (from Na-methyl-6-methoxy-d-tryptophan ethyl ester) are described. The syntheses have been completed in a highly stereocontrolled manner (>98% ee). Key steps included the asymmetric Pictet-Spengler reaction, enolate-mediated palladium cross-coupling reaction, and acid-catalyzed formation of the C(7)-C(17) bond. In addition, the triethylsilane/TFA-mediated incorporation of the 2alpha-H (11 to 12) and the borohydride generation of the C(17) hydroxyl function (R) were also stereospecific. The unique highly conjested carbon skeletons of the two alkaloids were completed in a concise manner and in regiospecific fashion.",10.1021/ja039798n,2004-01-21,0.6119586435224486
Journal of the American Chemical Society,Total Synthesis of Archazolid A,"The archazolids are complex polyketides isolated from the myxobacterium Archangium gephyra and are potent inhibitors of vacuolar type ATPases. Herein, we report the first total synthesis of archazolid A, which establishes unequivocally the relative and absolute configuration of this macrolide antibiotic. Key features of our synthesis include an aldol condensation for construction of the delicate ( Z, Z, E )-triene-system, an E -selective Heck reaction on a highly elaborate substrate, and a HWE macrocyclization to close the 24-membered macrolactone.",10.1021/ja071461o,2007-04-25,0.6119517260843838
Organic Letters,Asymmetric Total Synthesis of (−)-Aspidophylline A,"An asymmetric total synthesis of (-)-aspidophylline A has been accomplished. The key transformations include an asymmetric hydride transfer hydrogenation of an α,β-acetylenic ketone and a cationic gold(I)-catalyzed 6-exo-dig cyclization involving an alkynylindole/aminal formation cascade, which enables stereoselective establishment of the requisite quaternary carbon center.",10.1021/acs.orglett.7b00448,2017-03-23,0.6119457996886543
Organic Letters,"Efficient Synthesis of a Small Molecule, Nonpeptide Inhibitor of LFA-1","A three-stage process for the synthesis of LFA-1 inhibitor 1 from amine 4 with an overall yield of 65% is described. The key stage involves a Ph(3)PCl(2)-induced dehydration/cyclization of urea 6 followed by a regioselective bromination to give 1H-imidazo[1,2-a]imidazol-2-one 9. Br/Mg exchange of 9 followed by addition to SO(2) in THF and subsequent oxidation produces a sulfonyl chloride which is directly reacted with L-alaninamide using K(2)CO(3) as base in aqueous DMF/THF to give 1 in a one-pot operation. The process was implemented for the production of 1 on a metric ton scale.",10.1021/ol101960x,2010-09-10,0.6119452205427087
Organic Letters,"Asymmetric Total Syntheses of Two Phlegmarine-Type Alkaloids, Lycoposerramines-V and -W, Newly Isolated from<i>Lycopodium serratum</i>","Two new Phlegmarine-type alkaloids, lycoposerramines-V and -W, were isolated from Lycopodium serratum, and their structures including the absolute configuration were established by asymmetric total synthesis involving such key steps as Johnson-Claisen rearrangement, asymmetric allylation, and ring-closing metathesis (RCM)- or SmI(2)-mediated stereoselective piperidine ring construction.",10.1021/ol701871v,2007-09-01,0.6119309118962162
Tetrahedron,Synthesis of optically pure steroid intermediate by the novel use of -compound,,10.1016/s0040-4039(01)85646-x,1978-01-01,0.611929839678006
Organic Letters,Enantioselective Total Synthesis of (−)-Δ<sup>8</sup>-THC and (−)-Δ<sup>9</sup>-THC via Catalytic Asymmetric Hydrogenation and S<sub>N</sub>Ar Cyclization,"The highly efficient asymmetric total syntheses of (-)-Δ(8)-tetrahydrocannabinol ((-)-Δ(8)-THC) (13 steps, 35%) and (-)-Δ(9)-tetrahydrocannabinol ((-)-Δ(9)-THC) (14 steps, 30%) have been developed by using ruthenium-catalyzed asymmetric hydrogenation of racemic α-aryl cyclic ketones via dynamic kinetic resolution and intramolecular S(N)Ar cyclization.",10.1021/ol303351y,2013-01-24,0.6119144410559223
Synlett,Asymmetric Synthesis of (Trifluoromethyl)piperidines: Preparation of Highly Enantioenriched α′-(Trifluoromethyl)pipecolic Acids,"The first asymmetric synthesis of (trifluoromethyl)pipecolic acids is reported. The synthetic strategy involves as key step an intramolecular Mannich reaction of a homochiral α-Tfm-β-amino ketal, prepared with a high stereoselectively in four steps from a fluoral hemiacetal.",10.1055/s-2008-1072768,2008-05-01,0.6119007385370719
Synlett,A Highly Efficient Approach for the Synthesis of Cationic Lipid DOSPA,"A highly efficient strategy has been developed for the synthesis of the cationic lipid, N-[2-({2,5-bis[(3-aminopropyl)amino]-1-oxopentyl}amino)ethyl]-N,N-dimethyl-2,3-bis[(1-oxo-9-octadecenyl)oxy] salt with hydrogen chloride (DOSPA). It involves the linkage of a cationic head group and a hydrophobic moiety in the presence of the standard coupling reagents.",10.1055/s-2006-949636,2006-09-01,0.6118879870313139
Synlett,A Convergent Synthesis of the C31-C46 Fragment of Phorboxazoles,"A convergent synthesis of the C31-C46 fragment of phorboxazoles has been achieved. This involved the preparation of a C31-C39 aldehyde and a C40-C46 benzothiazole secondary ­sulfone followed by their coupling, employing modified Julia ole­fination as a key reaction.",10.1055/s-2004-829572,2004-01-01,0.6118788892865008
Organic Letters,Total Synthesis and Antimalarial Activity of Symplostatin 4,"The first total synthesis of symplostatin 4, a marine cyanobacterium-derived natural product, is described. Notable features of the route include the efficient preparation of three key fragments and final assembly to the natural product via sequential imide and amide couplings. Symplostatin 4 was also demonstrated to possess significant antimalarial activity (ED(50) of 74 nM against Plasmodium falciparum, strain 3D7).",10.1021/ol1024663,2010-11-04,0.6118729179243491
Journal of Organic Chemistry,Total Synthesis of the Branched Human Milk Oligosaccharide Lacto- <i>N</i> -neohexaose,"-neohexaose (LNnH) was accomplished in a total of 19 steps, starting from commercially available disaccharides─lactulose and lactose. The synthesis features regioselective silyl protection using tin chemistry, strategically designed [2+2] and [2+4] glycosylation reactions, and an orthogonal protection/deprotection sequence to ensure efficiency and selectivity. Careful optimization of reaction conditions and donor-acceptor combinations minimized the need for extensive chromatographic purifications, facilitating the isolation of crystalline intermediates in high yields. This streamlined approach provides a scalable and efficient route to LNnH, contributing to the synthetic accessibility of complex human milk oligosaccharides.",10.1021/acs.joc.5c02018,2025-11-07,0.6118675112744121
Organic Letters,One-Pot Assembly of the Rare Sugar Containing Trisaccharide Repeating Unit of <i>Pseudomonas putida</i> TSh-18,"Herein, we report the first total synthesis of the trisaccharide repeating unit of Pseudomonas putida TSh18, achieved through a one-pot glycosylation strategy. The synthesis addresses several challenges, including the synthesis of rare sugars d -Fuc p 4N 3 and d -Qui p NAc4NAc, installation of consecutive 1,2-cis linkages, and a late-stage amide coupling. Access to d -Fuc p 4N 3 was enabled for the first time by applying a double serial inversion approach. The synthesis was completed in 19 linear steps with an overall yield of 5.5%.",10.1021/acs.orglett.5c04587,2025-12-08,0.6118663610220019
Organic Letters,Asymmetric Synthesis of Tetrahydroquinolin-3-ols via CoCl<sub>2</sub>-Catalyzed Reductive Cyclization of Nitro Cyclic Sulfites with NaBH<sub>4</sub>,A new method for the construction of chiral 3-substituted tetrahydroquinoline derivatives based on asymmetric dihydroxylation and CoCl(2)-catalyzed reductive cyclization of nitro cyclic sulfites with NaBH(4) has been described with high optical purities. This method has been successfully applied in the formal synthesis of PNU 95666E and anachelin H chromophore.,10.1021/ol8028109,2009-01-21,0.6118624340440288
Journal of Organic Chemistry,"Total Synthesis of Cryptoconcatone D via Construction of 1,3-Diol Units Using Chiral Horner–Wittig Reagents","The modular synthesis of 1,3-polyols using a chiral phosphine oxide building block is reported. This versatile building block works in a repetitive way for the stereocontrolled synthesis of a tetraol key intermediate, which serves for the first total synthesis of the potentially anti-inflammatory natural product cryptoconcatone D. A new route toward the chiral building block is also presented: Starting from 2-deoxy-d-ribose, the optimized sequence now makes the use of the building block more attractive to practicing chemists again.",10.1021/acs.joc.2c01737,2022-10-04,0.6118607952320418
Journal of Organic Chemistry,Enantioselective Synthesis of the C1−C11 Fragment of Bafilomycin A<sub>1</sub>Using Non-Wittig and Desymmetrization Strategies,"The synthesis of the C1-C11 fragment 33 of bafilomycin A(1) was achieved. Intermediate ketone 16 was prepared in six steps from 4-oxopimelate 13. Desymmetrization of this ketone using Koga's chiral base followed by TMSCl quench furnished silyl enol ether 17 with excellent enantioselectivity. Further elaboration led to C5-C11 aldehyde 24, which was coupled with sulfone 3 to give lactone 25 in very good yield. The subsequent reductive elimination created the E-trisubstituted C4-C5 olefin with a 13:1 selectivity. The E C2-C3 double bond was then installed by methanol elimination, and compound 33 was obtained after a few functional group manipulations and a Negishi methyl zirconation.",10.1021/jo034018e,2003-05-16,0.6118585524260802
European Journal of Organic Chemistry,"Stereoselective Synthesis of <i>cis</i>‐1,3‐Dimethyltetrahydroisoquinolines: Formal Synthesis of Naphthylisoquinoline Alkaloids","Abstract A synthetic route to enantiopure cis ‐1,3‐dimethyltetrahydroisoquinolines, synthetic precursors of naphthylisoquinoline alkaloids, has been developed. The synthesis relies on the use of a phenylglycinol‐derived lactam as the starting enantiopure scaffold. After stereoselective opening of the oxazolidine ring, the C‐3 methyl substituent was installed, taking advantage of the lactam carbonyl group by stereoselective hydrogenation of an α‐methylenamide generated via a vinyl triflate.",10.1002/ejoc.201200798,2012-08-15,0.6118280058774968
Tetrahedron,Aza-annulation as a route to hydroxylated alkaloid lipids. The synthesis of (±)-prosopinine,,10.1016/0040-4039(94)88315-7,1994-03-01,0.6118254877114881
Organic Letters,"Enantioselective Synthesis of Chiral Substituted 2,4-Diketoimidazolidines and 2,5-Diketopiperazines via Asymmetric Hydrogenation","An enantioselective hydrogenation of 5-alkylidene-2,4-diketoimidazolidines (hydantoins) and 3-alkylidene-2,5-ketopiperazines catalyzed by the Rh/ f -spiroPhos complex under mild conditions has been developed, which provides an efficient approach to the highly enantioselective synthesis of chiral hydantoins and 2,5-ketopiperazine derivatives with high enantioselectivities up to 99.9% ee.",10.1021/acs.orglett.1c01894,2021-07-09,0.6118128047962492
Journal of Organic Chemistry,Synthesis of Novel Nocathiacin-Class Antibiotics. Condensation of Glycolaldehyde with Primary Amides and Tandem Reductive Amination of Amadori-Rearranged 2-Oxoethyl Intermediates,"Nocathiacin I (1) and nocathiacin IV (2) are novel indole-containing thiazolyl peptide antibiotics, which exhibit potent activity against key Gram-positive bacterial pathogens, including multi drug-resistant Staphylococcus aureus, Streptococcus pneumoniae, and Enterococcus faecium. New nocathiacins 7-12 were prepared from 2 by a condensation with glycolaldehyde followed by tandem reductive amination of the 2-oxoethyl intermediate 4. The latter was formed via Amadori rearrangement from initial 2-hydroxyethylideneamide 3. This transformation readily tolerates the complex architecture of nocathiacins and allows selective incorporation of water solubilizing groups to the primary amide in 2 without protecting group manipulation.",10.1021/jo020385z,2002-11-19,0.6118059570368898
Organic Letters,"Stereospecific Route to 5,11-Methanomorphanthridine Alkaloids via Intramolecular 1,3-Dipolar Cycloaddition of Nonstabilized Azomethine Ylide:  Formal Total Synthesis of (±)-Pancracine","The core structure of the complex pentacyclic 5,11-methanomorphanthridine alkaloids is constructed stereospecifically in one step employing an intramolecular [3 + 2]-cycloaddition of nonstabilized azomethine ylide as the key step. The strategy is demonstrated by accomplishing the formal total synthesis of (+/-)-pancracine. [reaction: see text]",10.1021/ol051321o,2005-07-21,0.6117949030720049
Organic Process Research & Development,Development of a Scalable Synthesis of <i>trans</i>-4-Fluorocyclohexylamine via Directed Hydrogenation,"Herein, a scalable and practical process to prepare trans -4-fluorocyclohexylamine hydrochloride ( 1a ) is described. By exploitation of the embedded gem -difluoride motif in the commercially available 4,4-difluorocyclohexanecarboxylic acid, a derived orthoester-masked acid underwent dehydrofluorination to provide the requisite vinyl fluoride for a directed hydrogenation event, enabling selective access to the trans -configuration of 1a .",10.1021/acs.oprd.0c00444,2020-11-23,0.6117795482414412
Synthesis,Protecting-Group-Free Total Synthesis of Anticancer (±)-Melotenine A,"Abstract Melotenine A, isolated from Melodinus tenuicaudatus, possesses significant anticancer activity against several human cancer cell lines. The synthesis of (±)-melotenine A was achieved without the use of any protecting groups in 11 steps with an overall yield of 6.7%. The key steps of our strategy were a Diels–Alder reaction to construct the tetracyclic framework and ring-closing metathesis to form the seven-membered ring of (±)-melotenine A.",10.1055/a-1633-8333,2021-09-03,0.611779411972458
Synthesis,A Simple and Efficient Synthesis of Fused Benzo[b]thiophene Derivatives,"Abstract A new approach to the synthesis of fused benzothiophene derivatives was developed based on iodine-promoted photocyclization of 4,5-diaryl-substituted thiophenes obtained in three steps from commercially­ available compounds. Comparative analysis showed that photochemical cyclization is a more efficient method for the preparation of fused benzo[b]thiophene derivatives, compared to oxidative coupling of 4,5-diaryl-substituted thiophenes in the presence of iron(III) chloride and palladium-catalyzed intramolecular arylation. This new approach provides an efficient synthesis of functionally substituted naphtho[2,1-b:3,4-b′]dithiophenes, phenanthro[9,10-b]thiophenes, benzo[1,2-b:3,4-b′:6,5-b′′]trithiophenes, as well as new fused heterocycles containing a pyridine ring and/or a carbazole moiety.",10.1055/a-1416-4924,2021-03-08,0.6117770983222028
Journal of Organic Chemistry,Total Synthesis of the Tetracyclic Indole Alkaloid Ht-13-B,"An expedient synthesis corroborating the proposed structure of the tetracyclic indole alkaloid ht-13-B is presented. Key synthetic steps include acyliminium ion allylation, a Mitsunobu reaction, a palladium-catalyzed Stille-Kelly cross coupling reaction, and a carbon monoxide-mediated palladium-catalyzed reductive N-heterocyclization. The chiral centers are ultimately derived from commercially available trans-4-hydroxy-l-proline.",10.1021/acs.joc.5b00433,2015-03-27,0.6117692102153631
European Journal of Organic Chemistry,"Synthesis of All the Diastereomers of 2‐Amino‐3‐hydroxy‐4,5‐dimethylhexanoic Acid","Abstract Herein, we describe an efficient stereoselective synthesis of all the diastereomers of 2‐amino‐3‐hydroxy‐4,5‐dimethylhexanoic acid. The γ‐branched carbon skeleton was set up by reaction of Garner's aldehyde with 2‐lithio‐3‐methyl‐2‐butene. Hydrogenation (Pd/C catalyst) of the tetrasubstituted olefin proceeded smoothly with acceptable stereoselectivity, depending on the diastereomer hydrogenated. The final compounds were then obtained in 12–18 % overall yield through intramolecular cyclization, Jones oxidation, and hydrolysis in 5–7 steps from Garner's aldehyde.",10.1002/ejoc.201301257,2013-11-19,0.6117646110698431
Synlett,A Facile One-Pot Synthesis of Isocoumestans via a Novel Extension of the Castro Cyclization of o-Iodophenols and Ethyl Propiolate,,10.1055/s-1991-20852,1991-01-01,0.6117583849890548
Organic Letters,Stereoselective Synthesis of the Disaccharide Unit of Incednine,A stereoselective synthesis of a fully protected version of the disaccharide unit (2) of incednine (1) is described. The synthesis of 2 proceeds in 4.7% overall yield from commercially available allyl α-d-galactopyranoside over the longest linear sequence.,10.1021/ol303093z,2012-12-18,0.6117520525496083
Organic Letters,Enantioselective Total Synthesis of (+)-Lucidumone via Organocatalytic Double Michael Addition,"A concise enantioselective total synthesis of (+)-lucidumone, a caged polycyclic meroterpenoid with a bicyclo[2.2.2]octane skeleton, was accomplished in 10 steps (LLS) starting from commercially available 2-cyclohexen-1-one. The key step features a quinine derivative-catalyzed double Michael addition that constructs the essential chiral bicyclo[2.2.2]octane framework with five contiguous stereocenters. Additional features include a Nef reaction and a one-pot Brønsted acid-promoted cyclization, which simultaneously form both Indane and hydrofuran ring systems.",10.1021/acs.orglett.5c03633,2025-09-10,0.6117469627027637
Organic Letters,Enantioselective Synthesis of Axially Chiral Multifunctionalized Biaryls via Asymmetric Suzuki–Miyaura Coupling,"Substituted 2-formylarylboronic acids were successfully employed as substrates for asymmetric Suzuki-Miyaura coupling. By virtue of the coupling with dialkoxyphosphinyl substituted naphthyl bromides and 2-nitronaphthalen-1-yl triflouromethanesulfonate, a series of novel multifunctionalized axially chiral biaryls were prepared in 53-97% yields with up to 97% ee using palladium-Cy-MOP as the catalyst. The methodology provides a highly efficient and practical strategy for the synthesis of novel multifunctionalized axially chiral biaryls.",10.1021/ol402666p,2013-10-18,0.6117457880090184
Synlett,Studies toward the Total Synthesis of Sorangicins: A Shortened Synthesis of the Dioxabicyclo[3.2.1]octane Core,"An access to the dioxabicyclo[3.2.1]octane core of sorangicin A was developed, using a keto lactone formation, a Mukaiyama–Michael reaction and an epoxide opening as the key steps.",10.1055/s-0033-1340182,2014-03-14,0.6117350957611047
Organic Process Research & Development,Practical Preparation and Resolution of 1-(2‘-Diphenylphosphino-1‘-naphthyl)isoquinoline:  A Useful Ligand for Catalytic Asymmetric Synthesis,"A practical synthesis of the atropisomerically chiral ligand QUINAP is described, followed by its efficient resolution into enantiomers by employing a deficiency of the chloropalladium complex derived from 1‘ -(R)- 1‘-(dimethylamino)-1-ethylnaphthalene. The X-ray structure of the ligand, which crystallises as a conglomerate, is reported.",10.1021/op034007n,2003-05-01,0.6117301245487232
Tetrahedron,Enantioselective synthesis of isoxazolidinyl thymine and cytosine nucleoides,"A diastereo- and enantioselective synthesis of isoxazolidinyl nucleosides (4) is described. The required isoxazolidine intermediate (16) was successfully prepared by the dioxolane-derived tautomerization of the corresponding lactol (13) which, in turn, was obtained from the reduction of the Michael adduct of N-methyl hydroxylamine and the unsaturated γ-lactone (5).",10.1016/0040-4039(96)00999-9,1996-07-01,0.6117292243651951
Journal of Organic Chemistry,"General Scope of 1,4-Diastereoselective Additions to a 2(3<i>H</i>)-Quinazolinone:  Practical Preparation of HIV Therapeutics","The practical and highly diastereoselective syntheses of CF(3)-substituted dihydroquinazolinones via 1,4-additions of nucleophiles to chiral auxiliary substituted 2(3H)-quinazolinones is described. This methodology is applied to the syntheses of the NNRTIs (nonnucleoside reverse transcriptase inhibitors) DPC 961 (1) and DPC 083 (2), which are useful for the treatment of HIV (human immunodeficiency virus). The synthesis of DPC 961 (1) requires three steps, proceeds in >55% overall yield from the keto-aniline 9, and gives synthetic access to DPC 083 (2). In addition, the scope of the new diastereoselective 1,4-addition chemistry is investigated. The first preparation of DPC 961 (1) described in this paper is a derivatization fractional crystallization protocol.",10.1021/jo0263162,2002-12-19,0.6117191147863047
Synlett,Stereoselective Formal Total Synthesis of (-)-Didemniserinolipid B,A formal total synthesis of (-)-didemniserinolipid B from L-(+)-tartaric acid is presented. Key features of the synthesis include construction of the bicyclic acetal core from bisdimethyl amide of tartaric acid and further elaboration by cross metathesis.,10.1055/s-0029-1217976,2009-09-10,0.6117189070401082
Journal of Organic Chemistry,Deoxygenation at C-4 and Stereospecific Branched-Chain Construction at C-3 of a Methyl Hexopyranuloside. Synthetic Approach to the Amipurimycin Sugar Moiety,"A five-step synthesis from 3 leading to a partially protected amipurimycin sugar moiety 14 in an overall yield of 47% is described and includes deoxygenation at C-4 and regio- and stereoselective construction of the branched chain. Deoxygenation at C-4 of 3 was possible by three different methods. Radical reduction with tri-n-butyltin hydride of the appropriate phenoxythiocarbonyl derivative afforded the desired deoxysugar 5 in 47% overall yield together with the secondary products 6 and 7 due to depivaloylation at C-2 and elimination of methanol. The most adequate deoxygenation procedure used the system Ph(3)P/I(2)/imidazole which led to the preparation of 5 in one step in 61% yield. When the system Ph(3)PBr(2)/Ph(3)P was tried, only 8 was formed due to elimination of methanol. The synthesis of 5 was then accomplished by reaction of 8 with methanol in the presence of triphenylphosphine hydrobromide in 37% overall yield. Branched-chain construction was accomplished by Wittig reaction of 5 with [(ethoxycarbonyl)methylene]triphenylphosphorane, followed by osmilation and reduction with lithium aluminum hydride. Isopropylidenation of 14 afforded 16 with a free hydroxy group at C-6 for chain elongation and further synthesis of amipurimycin.",10.1021/jo952220e,1996-01-01,0.6117156234513182
European Journal of Organic Chemistry,Synthesis of Deuterium‐Labelled 3‐Hydroxy‐<scp>L</scp>‐arginine: Comparative Studies on Different Protecting‐Group Strategies,"Abstract The β‐hydroxy‐α‐amino acid 3‐hydroxy‐ L ‐arginine is an important intermediate in biosynthetic pathways involving 2‐oxoglutarate (2‐OG) dependent Fe II oxygenases. It also plays an essential role in post‐translational modifications of ribosomal proteins. For profound studies on arginine‐hydroxylating enzymes, synthetic reference compounds are of utmost importance. However, the synthesis of β‐hydroxy‐α‐amino acids is often not trivial. In particular, the preparation of a densely functionalized compound such as 3‐hydroxy‐ L ‐arginine poses a challenge in terms of a protecting‐group strategy. We have previously established a concise synthesis of 3‐hydroxy‐ L ‐arginine that is suitable for the preparation of both 3‐epimers of this β‐hydroxy‐α‐amino acid. However, we have since observed a remarkable isomerization reaction upon removal of the hydrogenolytically cleavable protecting groups, thus limiting the reliability of our previously described route. In this paper, we report a comparative study of protecting‐group strategies for this synthetic route, including a newly developed, more robust pathway to the target amino acid. The versatility of this improved route is demonstrated by the synthesis of the deuterium‐labelled derivatives (3 R )‐ and (3 S )‐3‐hydroxy‐[5‐ 2 H]‐ L ‐arginine. These new isotope‐labelled arginine derivatives represent important tools for the elucidation of biosynthetic pathways, such as the formation of the arginine‐derived amino acid epicapreomycidine in the biosynthesis of muraymycin nucleoside antibiotics.",10.1002/ejoc.201501109,2015-11-24,0.6117141606012073
Journal of the American Chemical Society,"Callipeltoside A: Total Synthesis, Assignment of the Absolute and Relative Configuration, and Evaluation of Synthetic Analogues","The total synthesis of the novel antitumor agent callipeltoside A, as well as several analogues, is accomplished and allows assignment of the stereochemistry not previously established. A convergent strategy is employed wherein the target is dissected into three units-the core macrolactone, the sugar callipeltose, and a cyclopropyl bearing chain. The strategy for the synthesis of the macrolactone derives from employment of diastereoselective aldol reactions that emanate from an 11 carbon piece. The stereochemistry of the latter derives from the chiral pool and two asymmetric reactions-a ketone reduction using CBS-oxazaborolidine and a Pd catalyzed asymmetric allylic alkylation (AAA). The novelty of the latter protocol is its control of regioselectivity as well as absolute configuration. The trisubstituted olefin is generated using an alkene-alkyne coupling to create a trisubustituted olefin with complete control of geometry. The excellent chemo- and regioselectivity highlights the synthetic potential of this new ruthenium catalyzed process. The macrolactonization employs in situ formation of an acylketene generated by the thermolysis of a m-dioxolenone. Two strategies evolved for attachment of the side chain-one based upon olefination and a second upon olefin metathesis. The higher efficiency of the latter makes it the method of choice. A novel one pot olefin metathesis-Takai olefination protocol that should be broadly applicable is developed. The sugar is attached by a glycosylation by employing the O-trichloroacetimidate. This route provided both C-13 epimers of the macrolactone by using either enantiomeric ligand in the Pd AAA reaction. It also provided both trans-chlorocyclopropane diastereomers of callipeltoside A which allows the C-20 and C-21 configuration to be established as S and R, respectively. The convergent nature of the synthesis in which the largest piece, the macrolatone, require only 16 linear steps imparts utility to this strategy for the establishment of the structure-activity relationship. Initial biological testing demonstrates the irrelevance of the chloro substituent and the necessity of the sugar.",10.1021/ja0205232,2002-08-07,0.6117132618630492
Synthesis,"A New Synthesis of α,β-Unsaturated Diazo-ketones: An Improved Synthesis of 4-Diazo-3-oxo-1-phenyl-1-butene (Diazomethyl Styryl Ketone)",,10.1055/s-1974-23380,1974-01-01,0.6117127776491875
Synlett,"Asymmetric [2,3]-Wittig Rearrangement Approach to the Formal Synthesis of (+)-Brefeldin A","All articles of this category An asymmetric synthesis of the 2,4-disubstituted 1-cyclopentanal, a key precursor of brefeldin A, is described which involves as the key step an asymmetric [2,3]-Wittig rearrangement to control both the ring and side chain configurations. brefeldin A - [2,3]-Wittig rearrangement",10.1055/s-1995-5152,1995-09-01,0.6117118101603819
Organic Letters,"General Synthesis of Chiral α,α-Diaryl Carboxamides by Enantioselective Palladium-Catalyzed Cross-Coupling","A general synthesis of chiral α,α-diaryl carboxamides is developed by enantioselective cross-coupling between 2-bromo-2-aryl carboxamides and arylboronic acids, leading to a series of chiral α,α-diaryl carboxamides with various electronic properties and functionalities in moderate to excellent enantioselectivities and yields. The employment of a sterically bulky chiral P,P═O ligand L2 is critical for the reactivity and selectivity. This protocol is applied to an efficient asymmetric synthesis of a key intermediate of dopamine receptor agonist SKF 38393.",10.1021/acs.orglett.0c01489,2020-06-17,0.6116754208402219
Tetrahedron,Efficient one-pot synthesis of tryptamines and tryptamine homologues by amination of chloroalkynes,,10.1016/j.tetlet.2004.02.085,2004-03-06,0.611672400574664
Organic Letters,Total Synthesis of the All-Rare Sugar-Containing Pentasaccharide Repeating Unit of the O-Polysaccharide of <i>Plesiomonas shigelloides</i> Strain 302-73 (Serotype O1),"First total synthesis of the conjugation-ready pentasaccharide repeating unit of Plesiomonas shigelloides strain 302-73 (serotype O1) is reported. The complex target pentasaccharide is composed of all-rare amino sugars such as orthogonally functionalized d -bacillosamine, l -fucosamine, and l -pneumosamine linked through four consecutive α-linkages. The poor nucleophilicity of axial 4-OH of l -fucosamine and stereoselective glycosylations are the key challenges in the total synthesis, which was completed via a longest linear sequence of 27 steps in 3% overall yield.",10.1021/acs.orglett.1c02239,2021-07-22,0.6116679982566787
Organic Letters,Total Synthesis of (+)-Epiquinamide,"The stereoselective total synthesis of the novel quinolizidine alkaloid (+)-epiquinamide is presented, starting from the amino acid l-allysine ethylene acetal. Key steps in the synthesis involved a highly diastereoselective N-acyliminium ion allylation and a ring-closing metathesis reaction to provide the bicyclic skeleton. [reaction: see text]",10.1021/ol0515715,2005-08-09,0.611667418122639
Journal of the American Chemical Society,Biomimetic Enantioselective Total Synthesis of (−)-Siccanin via the Pd-Catalyzed Asymmetric Allylic Alkylation (AAA) and Sequential Radical Cyclizations,"(-)-Siccanin (1), a natural product possessing significant antifungal properties, was synthesized enantioselectively via a biomimetic route. This synthetic route features two sequential radical cyclizations: a Ti(III)-mediated radical cyclization of epoxyolefin 48 to construct the B-ring, and a Suarez reaction to establish the tetrahyrofuran ring. Chiral chroman moiety of siccanin was prepared based on our recent development of the Pd-catalyzed asymmetric allylic alkylation (AAA) of phenol trisubstituted allyl carbonates. Several other members of the siccanin family were also synthesized including siccanochromenes A (2), B (3), E (6), F (7), and the methyl ether of siccanochromene C (55). These studies may shed light on the biosynthesis of this novel family of compounds.",10.1021/ja048084p,2004-09-03,0.6116666753407408
Synthesis,Asymmetric Synthesis of 4′-Quaternary 2′-Deoxy-3′- and -4′-<i>epi</i>-β-<i>C</i>- and -<i>N</i>-Nucleosides,"A versatile and efficient route to both enantiomers of 4′-quaternary 2′-deoxy-3′- and -4′-epi-β-C- and -N-nucleosides is described. The asymmetric synthesis involves the SAMP/RAMP-­hydrazone α-alkylation methodology and diastereoselective nucleophilic 1,2-additions. Manipulation of the substituents in the anomeric position leads to the thermodynamically more stable β-anomers of excellent diastereo- and enantiomeric purity (>99% de and ee).",10.1055/s-2008-1072577,2008-05-01,0.6116616672141252
Synlett,A Stereoselective One-Pot Synthetic Approach to Functionalized Thietanes,"A facile synthetic route to functionalized thietanes has been developed by employing one-pot, high-yielding, and highly diastereoselective three-component coupling reaction of O,O-diethyl hydrogen phosphorodithioate, aromatic aldehydes, and activated olefins. The synthesis involves Michael addition of the dithioate to acrylonitrile/methyl acrylate followed by addition of the resulting carbanion to an aldehyde and intramolecular cyclization to afford 2-arylthietane-3-carbonitriles/carboxylates at room temperature.",10.1055/s-0028-1088119,2009-03-26,0.6116553941328146
Journal of Organic Chemistry,Development of a Synthetic Route to Vonoprazan via Atom Transfer Radical Cyclization,"High Resolution Image Download MS PowerPoint Slide In this Note, a new synthetic route to vonoprazan via atom transfer radical cyclization (ATRC) is described. The pivotal 1,3,5-trisubstituted pyrrole ring of vonoprazan has been accomplished by ATRC, the subsequent aromatization which simultaneously occurred with the introduction of N -methylamine moiety into the cyclic imine, and the sulfonylation at the 1-position of pyrrole. Furthermore, our approach enabled the synthesis of vonoprazan on a 0.7 kg scale without the isolation of intermediates throughout the process.",10.1021/acs.joc.4c02368,2025-02-26,0.6116546936915164
Journal of Organic Chemistry,"Enantiomeric Synthesis of <scp>l</scp>-(or 1‘<i>R</i>,2‘<i>S</i>)-Carbocyclic Cyclopropyl Nucleosides","The enantiomeric synthesis of carbocyclic cyclopropyl L-nucleosides has been accomplished from L-gulonic gamma-lactone. The key intermediate 3 was stereoselectively synthesized by DIBAL-H reduction and silyl protection followed by cyclopropanation from ester 2, which was in turn prepared from L-gulonic gamma-lactone (1) in five steps. Desilylation of cyclopropyl intermediate 3 gave alcohol 4, which was then converted to the urea derivative 5 and cyclopropylamine 7 by Curtius rearrangement of an acyl azide. The urea intermediate 5 was utilized to prepare thymine 10, uracil 11, and cytosine 14 derivatives. The hypoxanthine, adenine, and guanine nucleosides 21, 22, and 24 were synthesized from the amino intermediate 7.",10.1021/jo961523l,1997-04-01,0.6116538089352965
Organic Letters,Asymmetric Total Synthesis of Iheyamine B,"Herein, we report the first asymmetric total synthesis of iheyamine B from 2,2′-bisindoloazepinone using the stereoselective construction of the trans -vicinal 2-oxopropyl moiety in the azepine scaffold. The asymmetric decarboxylative allylic alkylation provided the α-allylated 2,2′-bisindoloazepinone intermediate. The subsequent conversion of the lactam moiety into another allyl group in a trans -selective manner followed by Wacker oxidation of each allyl unit to the corresponding 2-oxopropyl group completed the total synthesis of iheyamine B.",10.1021/acs.orglett.2c02788,2022-09-28,0.6116478968103006
Journal of Organic Chemistry,Core Structure of Eremophilanes and Bakkanes through Niobium Catalyzed Diels−Alder Reaction:  Synthesis of (±)-Bakkenolide A,"A suitable intermediate for the synthesis of eremophilanes and bakkanes was prepared by a highly regioselective and stereoselective one-step synthesis through a niobium catalyzed Diels-Alder reaction. As a demonstration of the versatility of this intermediate, a total synthesis of (+/-)-bakkenolide A is described.",10.1021/jo061722x,2006-11-18,0.6116412105867366
Journal of Organic Chemistry,New Strategy for the Synthesis of Substituted Morpholines,"A four-step synthesis of cis-3,5-disubstituted morpholines from enantiomerically pure amino alcohols is described. The key step in the synthesis is a Pd-catalyzed carboamination reaction between a substituted ethanolamine derivative and an aryl or alkenyl bromide. The morpholine products are generated as single stereoisomers in moderate to good yield. This strategy also provides access to fused bicyclic morpholines as well as 2,3- and 2,5-disubstituted products.",10.1021/jo9007223,2009-06-01,0.6116396883826112
Organic Letters,Ten-Step Synthesis of Potent Anticancer Steroid Withanolide D,"Withanolide D is a highly oxygenated steroid with a broad spectrum of biological activities (potent antitumor properties) and thus has stimulated considerable interest from synthetic chemists. Herein, we describe a concise 10-step synthesis of withanolide D, which features a Diels-Alder reaction with singlet oxygen, followed by a Kornblum-DeLaMare rearrangement to streamline functionalization of the critical A ring. A vinylogous aldol reaction was employed to forge the E ring with high regioselectivity and stereoselectivity. It should be noted that withanolide D could serve as the precursor for syntheses of six additional withanolide-type natural products, including withaferin A. This work establishes an efficient and modular route to withanolide D and related analogues, providing a robust platform for the synthesis of diverse withanolide derivatives as potential anticancer drug candidates.",10.1021/acs.orglett.5c05066,2025-12-31,0.6116367184795017
Journal of Organic Chemistry,Asymmetric Synthesis of (<i>S</i>)-(−)-Xylopinine. Use of the Sulfinyl Group as an <i>Ipso</i> Director in Aromatic S<sub>E</sub>,"Optically pure (S)-(-)-xylopinine 2 was prepared in three steps in 52% overall yield. Thus, condensation of the carbanion derived from (S)-4 with the (S)-(E)-sulfinylimine 5 gave a 2:1 mixture of tetrahydroisoquinolines 6a and 6b, differing only in configuration at sulfur. N-Desulfinylation of this mixture gave the diastereomeric sulfoxides which, without separation, were converted into (S)-(-)-xylopinine (2) with loss of the sulfinyl moieties under Pictet-Spengler conditions. This unprecedented ipso electrophilic substitution of a sulfinyl group may have synthetic implications beyond that described in this work.",10.1021/jo2007237,2011-05-12,0.6116239727676431
Angewandte Chemie International Edition,Divergent Synthesis of 17‐ <i>nor</i> ‐Cephalotane Diterpenoids through Developed Ynol‐diene Cyclization,"On the basis of a novel ynol-diene cyclization developed as a rapid access to tropone unit, the first divergent strategy to 17-nor-cephalotane diterpenoids has been successfully established. Combining with a bioinspired stereoselective dual hydrogenation, the divergent total synthesis of (+)-3-deoxyfortalpinoid F, (+)-harringtonolide, (-)-fortalpinoids M/N/P, and analog (-)-20-deoxocephinoid P have been achieved in 14-17 linear longest steps starting from commercially available materials.",10.1002/anie.202407757,2024-07-09,0.611619407184119
Tetrahedron,"Synthesis of novel 2H,8H-pyrano[2,3-f]chromene-2,8-diones from 8-formyl-7-hydroxy-4-methylcoumarin",,10.1016/j.tetlet.2013.07.047,2013-07-13,0.611611524523975
Synthesis,A Simple Synthesis of (±)-Sarkomycin,"A facile 6-step route to (±)-sarkomycin in 17% overall yield has been described via Michael addition of nitromethane to 2-hydroxymethyl-2-cyclopentenone, oxone-induced oxidative Nef reaction, and acid catalyzed dehydration.",10.1055/s-2005-861877,2005-01-01,0.6116110063425613
Organic Letters,Selective Synthesis of 1-Dialkylamino-2-alkylbicyclo-[1.1.1]pentanes,"Compared to the abundance of methodologies accessing 1-substituted and 1,3-disubstuted bicyclo[1.1.1] pentanes (BCPs), the synthetic accessibility of BCPs with substitutions at the methylene position has been limited. Herein, we report a selective synthesis of 1-dialkylamino-2-alkylbicyclo[1.1.1]pentanes from prefunctionalized starting materials. We also achieved further functionalizations of these 1,2-disubstituted BCPs and developed a synthesis of these compounds with minimum necessity of chromatographic purifications starting from 1,3-dichloroacetone. Finally, we also detailed the synthesis of a 1,2,3-trisubstituted BCP analogue.",10.1021/acs.orglett.0c03612,2020-11-10,0.6116104618098411
Synthesis,"Synthesis of 3-Oxo-2,3-dihydropyrrole Amino Acids as Chiral Dipeptidomimics","We describe the synthesis of a novel chiral dipeptide β-sheet mimic based on aminomethyl-3-oxo-2,3-dihydropyrrole carboxylic acids. The synthesis uses a palladium-catalyzed allylation with the chiral Trost ligand as a key step for the construction of a quaternary chiral center. This allows the enantioselective conversion of 2-carboxy-3-hydroxy-pyrrole into 3-oxo-2,3-dihydropyrrole-2-allyl-2-carboxylate. The allyl group is subsequently converted into an aldehyde or ester group. Peptide coupling of the 3-oxo-2,3-dihydropyrrole amino acid leads to more extended systems with partially constrained dipeptide units.",10.1055/s-2006-942497,2006-08-01,0.6116021811605781
Synthesis,"Synthesis of the First ""Inside-Outside"" Eight-Membered Ring via Ring-Closing Metathesis: A Total Synthesis of (±)-Asteriscanolide","All articles of this category A total synthesis of (±)-asteriscanolide which features two transition metal-mediated carbocyclic ring forming reactions as key elements of our strategy (Scheme 1) is described. The highly functionalized cyclopentenone 4 , the product of a cobalt-mediated Pauson-Khand [2 + 2 + 1] cycloaddition, is the key starting point for the synthesis. Excellent regiocontrol was obtained in the intermolecular Pauson-Khand reaction. Further synthetic manipulations of 4 led to diene 16 which underwent ring-closing metathesis using (PPh 3 ) 2 Cl 2 Ru(CHPh) to provide the desired ""inside-outside"" tricycle 17 . Conversion of 17 to 1 was achieved in a minimal number of steps. The synthesis of asteriscanolide has been achieved in 19 steps and 12% overall yield. ring-closing - metathesis - total synthesis - Pauson-Khand cycloaddition - transition metal mediated reactions",10.1055/s-2000-6302,2000-01-01,0.6115959962597216
Journal of Organic Chemistry,Reactivity of tricarbonyl(pentadienyl)iron(1+) cations: enantioselective synthesis of 5-HETE methyl ester,"The syntheses of racemic 5-HETE methyl ester (1) and of 5-HETE lactone (5-HL) were accomplished in 11 steps from tricarbonyl [l-(methoxycarbonyl)pentadienyl]iron(l+) hexafluorophosphate (2). A second synthesis of 1 from 2 in five steps was also achieved. Starting with optically active 5 the synthesis of (+)-l and (-)-l in high optical purity was realized. The stereochemistry of the 6,8-diene portion and the stereochemistry of the C5 asymmetric center of 1 were controlled by the (tricarbonyl)- iron adjunct.",10.1021/jo00060a033,1993-04-01,0.6115945827445021
Tetrahedron,Total synthesis of halichondrins: Enantioselective construction of a homochiral pentacyclic C1-C15 intermediate from d-ribose,,10.1016/s0040-4039(00)97476-8,1990-01-01,0.6115908549962399
Organic Process Research & Development,Development of a Green and Sustainable Manufacturing Process for Gefapixant Citrate (MK-7264) Part 1: Introduction and Process Overview,"A robust, green, and sustainable manufacturing process has been developed for the synthesis of gefapixant citrate, a P2X3 receptor antagonist that is under investigation for the treatment of refractory and unexplained chronic cough. The newly developed commercial process features low process mass intensity (PMI), short synthetic sequence, high overall yield, minimal environmental impact, and significantly reduced API costs. The key innovations are the implementation of a highly efficient two-step methoxyphenol synthesis, an innovative pyrimidine synthesis in flow, a simplified sulfonamide synthesis, and a novel salt metathesis approach to consistently deliver the correct active pharmaceutical ingredient (API) salt form in high purity.",10.1021/acs.oprd.0c00248,2020-10-16,0.6115890076594654
Synlett,"A New Versatile Route to the Synthesis of Novel Highly Substituted Series of 1,1´-Carbonyl-bispyrazole Derivatives",,,2014-03-12,0.6115868476785201
Tetrahedron,Pyrenyl-appended imidazolium receptor for selective fluorescence sensing of oxalic acid,,10.1016/j.tetlet.2011.10.014,2011-10-16,0.6115832654348686
Angewandte Chemie International Edition,9‐Membered Carbocycle Formation: Development of Distinct Friedel–Crafts Cyclizations and Application to a Scalable Total Synthesis of (±)‐Caraphenol A,"Explorations into a series of different approaches for 9-membered carbocycle formation have afforded the first reported example of a 9-exo-dig ring closure via a Au(III)-promoted reaction between an alkyne and an aryl ring as well as several additional, unique Friedel-Crafts-type cyclizations. Analyses of the factors leading to the success of these transformations are provided, with the application of one of the developed 9-membered ring closures affording an efficient and scalable synthesis of the bioactive resveratrol trimer caraphenol A. That synthesis proceeded with an average yield of 89% per step (7.8% overall yield) and has provided access to more than 600 mg of the target molecule.",10.1002/anie.201311299,2014-02-23,0.6115832622032709
Synthesis,Benzothiazines in Synthesis: A Route to Chiral Cyclobutanes,"Using enantiomerically pure benzothiazines as templates, enantiomerically pure cyclobutanes were prepared. Such compounds are potentially interesting synthetic intermediates. The sequence developed for the preparation of these compounds, as well as some of their chemistry, is described.",10.1055/s-2008-1032146,2008-02-01,0.6115807129040892
Tetrahedron,An improved synthesis of the scyphostatin side-chain,,10.1016/j.tetlet.2004.01.156,2004-02-21,0.6115643547887525
Tetrahedron,Application of chiral (E)-crotylsilanes in synthesis: The asymmetric synthesis of the C19C34 spiroketal fragment of rutamycin B,"The asymmetric synthesis of the spiroketal fragment of rutamycin B is reported employing allylsilane bond construction methodology for the introduction of five of the eight stereogenic centers. In this paper, the construction of the C19C28 and C29C34 fragments as well as their coupling through an alkylation reaction of a lithiated N,N-dimethylhydrazone are described.",10.1016/s0040-4039(97)00096-8,1997-02-01,0.6115576586625316
Journal of Organic Chemistry,Gram Scale Synthesis of Membrane-Active Antibacterial 4-Quinolone Lead Compound,"An improved method for the synthesis of a new quinolone class of antibiotics, which are exceptionally potent against gram-positive bacteria, has been developed and the structure confirmed by single-crystal X-ray analysis. In the course of synthesis, using either Chan–Lam coupling or Buchwald–Hartwig amination, we have shown that the careful choice of protecting group at the C4 position of the quinoline is required for selective amination at the C5 position and subsequent deprotection to avoid the formation of a novel pyrido[4,3,2- de ]quinazoline tetracycle.",10.1021/acs.joc.3c00239,2023-04-18,0.6115549857835902
Synlett,Synthesis of 2-Carboxy-6-hydroxyoctahydroindole (Choi) Core Unit for the Synthesis of Aeruginosins,"The synthesis of N,O-protected 2-carboxy-6-hydroxyoctahydroindole (Choi) core unit for the synthesis of aeruginosins has been described.",10.1055/s-2003-36238,2002-01-01,0.6115540217718841
Synthesis,"A Novel Synthesis of Dithieno[2,3-<i>b</i>:3′,2′-<i>d</i>]thiophene and its Bromo Derivatives","Two new approaches to multigram synthesis of dithieno[2,3-b:3′,2′-d]thiophene are described. Various mono-, di-, tri- and tetrabromides of dithieno[2,3-b:3′,2′-d]thiophene are prepared in good yield.",10.1055/s-2003-36258,2003-01-01,0.6115505623822326
Journal of Organic Chemistry,Convenient Method of Synthesizing 3-Ethoxycarbonyl Indoles,"We have developed a convenient two-step procedure for the synthesis of 3-ethoxycarbonyl indoles from commercially available materials. The two-step procedure involves the synthesis of 2-aryl-3-hydroxypropenoic acid ester, followed by a catalytic reduction. This method is efficient, simple, and selective.",10.1021/jo0601821,2006-05-11,0.6115455005961207
Tetrahedron,A convergent preparation of the CHK1 inhibitor MK-8776 (SCH 900776),,10.1016/j.tetlet.2016.04.102,2016-05-03,0.6115449418407124
Journal of Organic Chemistry,Asymmetric Synthesis of Chiral Spiroketal Bisphosphine Ligands and Their Application in Enantioselective Olefin Hydrogenation,"A series of chiral spiroketal bisphosphine ligands containing 1,1'-spirobi(3 H,3' H)isobenzofuran backbones was accessed through asymmetric synthesis and subsequently tested in enantioselective Rh-catalyzed hydrogenation of α-dehydroamino acid esters. The ligand providing the highest enantioselectivity (up to 99.5%) was obtained in seven steps in an overall 38% yield. The synthesis could be performed on a gram scale, and no kinetic resolution of enantiomers is required. Overall, the developed ligand provides an easily accessible alternative to SDP ligands as well as other chiral bisphosphine ligands.",10.1021/acs.joc.8b01693,2018-09-12,0.6115349883896948
Synlett,Palladium-Mediated Synthesis of Calothrixin B,"An efficient synthesis of the indolo[3,2-j]phenanthridine alkaloid calothrixin B is described. The relative ease and high yields of this synthesis make this an attractive route for the preparation of calothrixin B derivatives for structure-activity relationship studies.",10.1055/s-2007-984520,2007-07-01,0.6115287198691988
Tetrahedron,An improved Pfitzinger reaction: Eco-efficient synthesis of quinaldine-4-carboxylates by TMSCl-mediated,,10.1016/j.tetlet.2017.08.014,2017-08-08,0.6115247642888232
Organic Letters,Six-Step Synthesis of (<i>S</i>)-Brevicolline from (<i>S</i>)-Nicotine,"[reaction: see text] A six-step synthesis of (S)-brevicolline from (S)-nicotine is reported. Regioselective trisubstitution of the pyridine ring of nicotine, followed by successive Suzuki cross-coupling and Buchwald amination reactions, afforded the enantiopure beta-carboline alkaloid, brevicolline.",10.1021/ol061334h,2006-07-13,0.611519183401566
Journal of Organic Chemistry,An Improved Synthesis of the Selective EP4 Receptor Agonist ONO-4819,"An improved synthesis of the highly selective EP4-receptor agonist ONO-4819 has been developed. The previous synthesis suffered from several drawbacks, in which a critical one is the difficulty in the removal of byproducts leading to unsatisfactory quality of the active pharmaceutical ingredient (API). Furthermore, on stereoselective reduction of an enone intermediate by binaphthol-modified lithium aluminum hydride, low concentration of the reaction conditions and tedious purification procedures to remove excess binaphthol were critical issues for the manufacturing process of the API. In the improved process, we have developed improved conditions using gamma-thiobutyrolactone as sulfur source instead of potassium thioacetate to introduce the sulfur-containing C4 side chain without formation of byproducts. For stereoselective synthesis of the chiral alcohol, (-)-DIP-chloride reduction is found to be the best method, which can improve not only the enantioselectivity but also the workload for removing the chiral modifier in a purification process. Furthermore, benzoyl and tert-butyldimethylsilyl groups as protecting groups for hydroxyl functions were used for precise process controls of all intermediates. By changing these protecting groups, the purity of ONO-4819 was strictly controlled through crystalline intermediates. Thus, an improved robust process for ONO-4819 with a high chemical purity was developed.",10.1021/jo901497u,2009-10-05,0.6115146098810205
Angewandte Chemie International Edition,Catalytic Asymmetric Synthesis of α‐Arylpyrrolidines and Benzo‐fused Nitrogen Heterocycles,"Herein, we report a practical two-step synthetic route to α-arylpyrrolidines through Suzuki-Miyaura cross-coupling and enantioselective copper-catalyzed intramolecular hydroamination reactions. The excellent stereoselectivity and broad scope for the transformation of substrates with pharmaceutically relevant heteroarenes render this method a practical and versatile approach for pyrrolidine synthesis. Additionally, this intramolecular hydroamination strategy facilitates the asymmetric synthesis of tetrahydroisoquinolines and medium-ring dibenzo-fused nitrogen heterocycles.",10.1002/anie.201814331,2019-01-19,0.6115089020097684
Journal of the American Chemical Society,Divergent Synthesis of Antiviral Diterpenes Wickerols A and B,"Wickerols A and B are diterpene natural products that have a novel fused 6–5–6–6 ring framework and exhibit potent antiviral activity against the H1N1 type A influenza virus. Herein, we report a divergent synthesis of wickerols A and B in 16 and 15 steps, respectively, from commercial sitolactone. The key reactions of the synthesis are a SmI 2 -mediated intramolecular ketone–allylic acetate reductive cyclization, a Claisen rearrangement, and an intramolecular alkylation/aldol reaction that rapidly assembled the compact tetracyclic core framework in a stereocontrolled manner. The work described herein allowed us to confirm the absolute configurations of wickerols A and B.",10.1021/jacs.9b11838,2020-02-19,0.6115064206344774
Journal of Organic Chemistry,An Efficient Synthesis of Valienamine via Ring-Closing Metathesis,"An efficient synthesis of valienamine is described. Valienamine was synthesized starting from commercially available 2,3,4,6-tetra-O-benzyl-D-glucose in nine steps, using ring-closing metathesis of (4S,5S,6S)-4,5,6-tribenzyloxy-7-(benzyloxymethyl)octa-1,7-dien-3-ol as a key step.",10.1021/jo047735x,2005-03-17,0.611502250872563
Organic Process Research & Development,Scalable Process Design for a PDE10A Inhibitor Consisting of Pyrazolopyrimidine and Quinoxaline as Key Units,"In this study, research and development for the synthetic process of a PDE10A inhibitor are described; in particular, an efficient regioselective construction of the quinoxaline unit, a cost-effective pyrazolo[1,5- a ]pyrimidine formation, and a cost-saving approach in a nucleophilic aromatic substitution (S N Ar) reaction by introducing oxazolidinone as an electron-withdrawing group to a chloropyrazolo[1,5- a ]pyrimidine core are key points. The newly developed process has been successfully scaled up to 40 kg. Furthermore, a one-pot tandem reaction from aminopyrazole to dichloropyrazolo[1,5- a ]pyrimidine by activating malonic acid with POCl 3 was discovered. The finding contributed to avoiding isolation of the hygroscopic pyrazolo[1,5- a ]pyrimidin-5(4 H )-one intermediate, which caused complicated filtration and drying processes observed in the first scale-up campaign.",10.1021/acs.oprd.9b00068,2019-03-15,0.6114943580565895
Organic Letters,Concise Total Synthesis of the Marine Natural Product Ageladine A,"A total synthesis of ageladine A has been achieved by exploiting a Pictet-Spengler-type condensation between 2-aminohistamine and 4,5-dibromo-2-formylpyrrole as the key step.",10.1021/ol061584y,2006-08-01,0.6114922896676793
Journal of Organic Chemistry,Stereoselective Synthesis of the Tricyclic Core of (−)-Callophycoic Acid A,"Two stereocontrolled routes to the tricyclic core of (-)-callophycoic acid A are described. Our synthetic strategy relied on stereoselective allylboration using a new allylboronate reagent to construct the all-carbon quaternary stereocenter in the core, followed by efficient radical cyclization or palladium-catalyzed reductive cyclization to form its multisubstituted cyclohexane ring. The tetrahydrooxepin ring was constructed by intramolecular etheration. This study provides the first method for the stereoselective synthesis of the characteristic tricyclic skeleton of callophycoic acids.",10.1021/acs.joc.9b03114,2020-01-10,0.6114882535654351
Angewandte Chemie International Edition,Concise Total Synthesis of Tronocarpine,"A concise total synthesis of tronocarpine, a chippiine-type indole alkaloid, was accomplished. The key feature of this total synthesis is a one-pot construction of the pentacyclic skeleton containing an azabicyclo[3.3.1]nonane core by tandem cyclization from an indole derivative with all carbon side chains and functional groups. This tandem cyclization consists of α,β-unsaturated aldehyde formation, intramolecular aldol reaction, six-membered lactamization, azide reduction, and seven-membered lactamization. The stereochemical outcome in this tandem cyclization is controlled by the stereocenter at the C14 position. This strategy can be utilized to synthesize other chippiine-type alkaloids with azabicyclo[3.3.1]nonane skeletons.",10.1002/anie.202009966,2020-09-24,0.6114851957340487
European Journal of Organic Chemistry,A Pauson–Khand Approach to New Carbocyclic Nucleoside Analogs,"Abstract The synthesis of three new carbocyclic nucleoside analogs (CNAs) with the nucleobase attached to a 3′‐hydroxymethylcyclopent‐2′‐en‐1′‐yl scaffold is reported. A variety of symmetric dienynes (propargylic acetals of type 11 ) were used as substrates in a cobalt‐mediated Pauson–Khand (PK) reaction to give bicyclic cyclopentenone derivatives of type rac ‐ 12 with high diastereoselectivity. These compounds are valuable building blocks for the synthesis of structurally diverse CNAs with a high biological potential as apoptosis‐inducing agents. Starting from the PK product rac ‐ 12a , the synthesis of 4′‐trialkylsilyloxyethyl‐substituted nucleosides rac ‐ 18 and rac ‐ 19 (with 5‐bromouracil and 6‐chloropurine as a nucleo‐base, respectively) was accomplished in seven steps (28 % and 37 % overall yield). The regio‐ and diastereoselective nucleobase (NB) introduction was achieved by Pd 0 ‐catalyzed allylic substitution. Starting from the PK product rac ‐ 12e , the 2′‐phenyl‐4′‐trialkylsilyloxymethyl‐substituted CNA rac ‐ 17 was prepared (6 steps, 29 % yield)by exploitingan alternative protocol — a Mitsunobu reaction — for the NB introduction. The key intermediates 12a and 12e were obtained in virtually enantiopure form by kinetic resolution by means of oxazaborolidine‐catalyzed borane reduction (CBS reduction) in the presence of a ( R )‐diphenylprolinol‐derived B ‐methyl oxazaborolidine catalyst. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2005)",10.1002/ejoc.200400886,2005-04-01,0.6114724987911959
Journal of Organic Chemistry,Applications of Crotonyldiisopinocampheylboranes in Synthesis:  Total Synthesis of Restrictinol,"The total synthesis of restrictinol, the hydrolysis product of the antifungal natural product restricticin, starting from commercially available methyl (S)-(+)-3-hydroxy-2-methylpropionate is described. Key stages in the strategy involved (i) the use of Brown's allylboration chemistry to construct an acyclic intermediate bearing three of the four stereogenic centers of the natural product, (ii) formation of a C-glycosidic vinyl iodide, and (iii) introduction of the triene side chain via a Suzuki coupling reaction.",10.1021/jo9815305,1998-12-11,0.6114624597409114
Journal of Organic Chemistry,Amphidinolides F and C2: An Odyssey in Total Synthesis,"Amphidinolides F, C, C2, and C3 are marine natural products isolated from dinoflagellates Amphidinium species. They share the same macrolactone core, with the difference between them residing at the side chain level. A predominant feature of these amphidinolides is the presence of two trans -THF rings inside the macrolactone core, which is thought to be built by C-glycosylation with titanium enolate of N -acetyl oxazolinethiones. Thus, the original strategy for their total synthesis was based on the assembly of three main fragments corresponding to C 1 –C 9, C 10 –C 19, and C 20 –C 29 or C 20 –C 34 disconnections. Whereas synthesis of all fragments was successful, the C-glycosylation reaction between C 19 and C 20 turned out to be an issue. Therefore, a second route was designed. The new disconnection between C 17 and C 18 was based on a sulfone addition and a desulfonylation sequence. Our convergent strategy allowed the total synthesis of amphidinolide F and enabled a new unifying route toward the synthesis of amphidinolides C, C2, and C3 using a late-stage divergent approach. Although there were unsatisfying yields at some critical steps, our work culminated into the first total synthesis of amphidinolide C2.",10.1021/acs.joc.1c02458,2022-01-07,0.6114618798911086
Organic Letters,Catalytic Enantioselective Total Synthesis of (+)–Lycoperdic Acid,"A concise enantio- and stereocontrolled synthesis of (+)-lycoperdic acid is presented. The stereochemical control is based on iminium-catalyzed Mukaiyama-Michael reaction and enamine-catalyzed organocatalytic α-chlorination steps. The amino group was introduced by azide displacement, affording the final stereochemistry of (+)-lycoperdic acid. Penultimate hydrogenation and hydrolysis afforded pure (+)-lycoperdic acid in seven steps from a known silyloxyfuran.",10.1021/acs.orglett.0c00772,2020-03-27,0.6114528238220107
Organic Process Research & Development,Process Development of the Novel LpxC Inhibitor T-1228. Part 3: Optimization of the Deprotection Reaction and the Crystallization for the Final Step of API Synthesis,"The novel LpxC inhibitor T-1228 is a candidate drug molecule for multidrug-resistant Gram-negative bacterial infection. We developed a process chemistry route to T-1228. The final step of T-1228 drug substance synthesis consists of a deprotection reaction under acidic conditions and a crystallization process incorporating polymorph control. The process parameters of the deprotection reaction were optimized through a Design of Experiments (DoE) study to limit the formation of a critical impurity. The production method established for the crystallization process was developed by means of process analytical technology (PAT): it controls the quality and particle size of the drug substance and selectively yields only the desired crystal polymorph. By applying the newly developed process chemistry route, we have successfully manufactured T-1228 at 24% total yield from commercially available 1,3-diethyl 2-bromo-2-methylpropanedioate.",10.1021/acs.oprd.5c00167,2025-11-05,0.6114471621654023
Tetrahedron,Gram-scale stereoselective synthesis of next generation of Trk Inhibitor LOXO-195,,10.1016/j.tetlet.2022.154019,2022-07-16,0.6114409914624424
European Journal of Organic Chemistry,Synthesis of Imidazolo-Piperidinopentoses as Nagstatine Analogues,"The syntheses of the four imidazolo-piperidino-pentoses 3−6, which belong to the D-series, and of their L-enantiomers, ent-3 to ent-6, are reported. Ascorbic acid and isoascorbic acid were converted over several steps into the L-threo/L-erythro- and the D-erythro/D-threo-configured aldotetroses, respectively, which are the key building blocks for the eight target imidazolo-pentoses cited above. Nucleophilic addition of a metallated imidazole to any one of these four aldotetroses gave the corresponding two diastereomeric adducts, intramolecular cyclisation of which provided the expected bicyclic target molecules, with some protection and deprotection steps being unavoidable prerequisites. The structures and configurations of all eight piperidinoses in Scheme 1 were determined unambiguously, by a combination of 1H/13C NMR spectroscopy, circular dichroism (CD) and [α]D values, in conjunction with single-crystal X-ray diffraction analyses of the L-arabino and D-lyxo azasugars ent-3 and 6. Although lacking the hydroxymethylene group in the C(5) position, the overall structure of these eight stereomers strongly resembles that of the natural product nagstatine (1), a potent inhibitor of N-acetyl-β-D-glucosaminidase. As a matter of fact, after examination of the inhibitory properties of these imidazolo-piperidinoses against six commonly encountered glycosidases, we observe that the L-arabino imidazolo-sugar ent-3 is a potent inhibitor in this series, with Ki = 1 μM both with a β-glucosidase and with a β-galactosidase. The D-ribo and D-xylo stereomers 4 and 5 proved to be inhibitors of a β-glucosidase of similar magnitude (4: Ki = 20 μM; 5: Ki = 17 μM), the other stereomers being either modest to poor inhibitors, or showing no inhibition at all.",10.1002/1099-0690(200111)2001:21<4111::aid-ejoc4111>3.0.co;2-7,2001-11-01,0.6114374826345829
European Journal of Organic Chemistry,"Chemoenzymatic Asymmetric Total Synthesis of Nonanolide (<i>Z</i>)‐Cytospolides D, E and Their Stereoisomers","Abstract Chemoenzymatic asymmetric total synthesis of the ( Z )‐isomer of the naturally occurring decanolide cytospolides D, E and six stereoisomers is reported. The main highlight of the synthetic venture involves ring‐closing metathesis (RCM) reaction of a suitably functionalized ester compound, which was assembled by the Yamaguchi coupling of the required acid and alcohol fragments. The alcohol fragment was accessed by two alternative chemoenzymatic processes, one being hydroxynitrile lyase mediated hydrocyanation, whereas lipase‐catalyzed transesterification was the key sep in the second route. The acid fragment was constructed by an enantioselective enzymatic desymmetrization (EED) of prochiral 2‐methyl‐1,3‐propanediol and Corey–Bakshi–Shibata (CBS) mediated stereoselective carbonyl reduction.",10.1002/ejoc.201301365,2013-11-26,0.6114330067095808
Journal of Organic Chemistry,Asymmetric Total Synthesis and Revised Structure of Cephalezomine H,"A revised structure of cephalezomine H, Cephalotaxus alkaloids, is presented. The originally assigned and revised structures of cephalezomine H were synthesized from the key intermediate for the synthesis of (-)-cephalotaxine.",10.1021/jo901689a,2009-09-04,0.6114270358538901
European Journal of Organic Chemistry,Stereoselective Synthesis of the β‐Amino Acid Moiety of Fijiolide A,"An enantioselective synthesis of the β‐amino acid moiety of fijiolide A is described. Starting from eugenol, two sulfamates could be obtained on gram scale as substrates for an enantioselective C–H amination using Rh 2 ( R/S ‐nap) 4 . Acylation and ring opening of the resulting oxathiazinanes, followed by stepwise oxidation of the corresponding amino alcohol and TES‐protection of the catechol gave rise to Cramer's amino acid fragment from the total synthesis of fijiolide A.",10.1002/ejoc.201801623,2018-11-27,0.6114203063103991
Organic Letters,Gold(III) Chloride Catalyzed Synthesis of 1-Cyanoisoindoles,"A two-step synthesis of 1-cyanoisoindoles starting from ethynylbenzaldehyde is presented. The key step is a mild, high-yielding, gold-catalyzed rearrangement of N-allylic aminonitriles.",10.1021/ol902031f,2009-10-05,0.6114118300431319
Synthesis,"A New Synthetic Route to 1,3-Benzoxazepines","All articles of this category A novel method for the synthesis of 5-hydroxy-1,3-benzoxazepines 5 utilizing the Staudinger reaction followed by an intramolecular aza-Wittig reaction, from o -acyloxyphenacyl azides 2 is reported.",10.1055/s-1990-26901,1990-01-01,0.6113998632482072
Tetrahedron,An efficient synthesis of 4-alkenyl/alkynyl-6-methyl-2-pyrones via Pd-catalysed coupling on 4-bromo-6-methyl-2-pyrone,,10.1016/s0040-4039(02)02207-4,2002-12-01,0.6113954876053711
Synlett,A New Access to Polyhydroxylated Pyrrolidines from Epoxyaldehydes,"All articles of this category Our approach relies on the stereocontrolled vinylation of a chiral α , β -epoxyimine derived from the corresponding aldehyde. Regioselective opening of the oxirane with carbonate anion allowed the formation of an oxazolidinone intermediate from which the glucosidase inhibitor 1,4-dideoxy-1,4-imino-d-glucitol (1 4 ) was synthesised. Direct cyclisation into a 2-vinyl-3,4-epoxypyrrolidine afforded a valuable intermediate for the preparation of synthetic azasugar analogues. asymmetric synthesis - azasugars - epoxides - imines - 1,4-dideoxy-1,4-imino-d-glucitol",10.1055/s-2001-14593,2001-01-01,0.611391099899945
Journal of Organic Chemistry,Enantioselective Total Syntheses of (+)-Fendleridine and (+)-Acetylaspidoalbidine,"Enantioselective syntheses of hexacyclic aspidoalbidine alkaloids (+)-fendleridine (2) and (+)-acetylaspidoalbidine (3) are described. These syntheses feature an asymmetric decarboxylative allylation and photocyclization of a highly substituted enaminone. Also, the synthesis highlights the formation of a C19-hemiaminal ether via a reduction/condensation/intramolecular cyclization cascade with the C21-alcohol. The present synthesis provides convenient access to the aspidoalbidine hexacyclic alkaloid family in an efficient manner.",10.1021/acs.joc.9b00145,2019-04-02,0.6113902657026484
Angewandte Chemie International Edition,Total Synthesis of the Diterpenoid (+)‐Harringtonolide,"Described herein is the first asymmetric total synthesis of (+)-harringtonolide, a natural diterpenoid with an unusual tropone imbedded in a cagelike framework. The key transformations include an intramolecular Diels-Alder reaction and a rhodium-complex-catalyzed intramolecular [3+2] cycloaddition to install the tetracyclic core as well as a highly efficient tropone formation.",10.1002/anie.201605879,2016-08-16,0.6113856592695307
Angewandte Chemie International Edition,Total Synthesis of Natural Myriaporones,"The relative and absolute configuration of the cytotoxic myriaporones (e.g. 4) was assigned by their total synthesis from aldehyde 1. Key steps included aldol reactions with chiral oxazolidinone 2 and with Weinreb amide 3. TBS=tert-butyldimethylsilyl, PMB=p-methoxybenzyl.",10.1002/anie.200353313,2004-03-17,0.6113784859796554
Journal of Organic Chemistry,"Cp<sub>2</sub>TiCl-Mediated Reductive Cyclization: Total Synthesis of Pestalotiolactone A, Myrotheciumone A, and Scabrol A","The first stereoselective total syntheses of fungal secondary metabolites monoterpenoid (+)-pestalotiolactone A, meroterpenoid (−)-myrotheciumone A, and iridoid lactone (+)-scabrol A have been accomplished in an expedient unified approach starting from d -(+)-malic acid employing an epoxide opening-radical cyclization protocol initiated by Cp 2 Ti(III)Cl as a key step to assemble the core bicyclic lactone moieties of these molecules with complete diastereoselective control. Finally, the deoxygenation and methylation delivered the target natural products.",10.1021/acs.joc.1c01243,2021-08-02,0.6113779434968417
Synlett,"A Novel Method for Deprotection of <i>N</i>-9-Phenylfluoren-9-yl Group Using Iodine Catalyst: Simple Synthesis of (<i>2S</i>,<i>3R</i>,<i>4R</i>)-3,4-Dihydroxyproline","All articles of this category Iodine was found to be an efficient catalyst for the deprotection of the N -phenylfluoren-9-yl (Pf) group in tertiary amine and promote an intramolecular amination. A facile and economical synthesis of ( 2S , 3R , 4R )-3,4-dihydroxyproline was accomplished via iodine promoted cyclization and deprotection. iodine - cleavage of N -9-phenylfluoren-9-yl - dihydroxyproline - one-pot cyclization",10.1055/s-1999-2688,1999-05-01,0.6113658982017425
Synlett,"Synthetic Route Optimization of PF-00868554, An HCV Polymerase Inhibitor in Clinical Evaluation","This paper describes the optimization efforts to establish an enabling synthesis to provide multigram quantity of PF-00868554, an HCV polymerase inhibitor currently in phase II clinical evaluations.",10.1055/s-0029-1219352,2010-01-25,0.6113624283551264
Journal of Organic Chemistry,Stereocontrolled Construction of 1-Vinylindanes via Intramolecular Cyclization of <i>o</i>-Cinnamyl Chalcones,"In this paper, a concise route for the synthesis of 1-vinylindanes is described, including (i) NaBH 4 -mediated reduction of o -cinnamyl chalcones and (ii) sequential BF 3 ·OEt 2 -mediated intramolecular annulation of the resulting alkenols. The plausible mechanism is proposed and discussed herein. This protocol provides highly effective stereocontrolled cinnamyl-enone cross-coupling to construct three contiguous trans - trans stereocenters and one ( E )-configured alkenyl or styryl group.",10.1021/acs.joc.8b01729,2018-08-18,0.6113584386327025
Organic Letters,Concise Syntheses of (+)-Macrosphelides A and B,"[reaction: see text]. Unified and highly convergent total syntheses of (+)-macrosphelides A and B are described. Key features of the syntheses include (1) concise synthesis of the optically active delta-hydroxy-gamma-keto alpha,beta-unsaturated acid fragment via the direct addition of a trans-vinylogous ester anion equivalent to the readily available Weinreb amide and (2) facile construction of the 16-membered macrolide core of the macrosphelide series via an intramolecular nitrile-oxide cycloaddition (INOC).",10.1021/ol0508429,2005-06-18,0.6113503797478361
Tetrahedron,An efficient approach for the synthesis of the hexahydroazepine segment of balanol,,10.1016/s0040-4039(02)00681-0,2002-05-01,0.6113486042401257
Tetrahedron,An efficient approach toward the synthesis of the A/B rings of ouabain,,10.1016/j.tetlet.2006.08.047,2006-09-02,0.6113486042401257
Journal of the American Chemical Society,Enantioselective Total Synthesis of (−)-Hunterine A Enabled by a Desymmetrization/Rearrangement Strategy,"The first enantioselective total synthesis of (-)-hunterine A is disclosed. Our strategy employs a catalytic asymmetric desymmetrization of a symmetrical diketone and subsequent Beckmann rearrangement to construct a 5,6-α-aminoketone. A convergent 1,2-addition joins a vinyl dianion nucleophile and the enantioenriched ketone. The endgame of the synthesis features an aza-Cope/Mannich reaction and azide-olefin dipolar cycloaddition to complete the pentacyclic ring system. The synthesis is completed through a regioselective aziridine ring opening.",10.1021/jacs.3c13590,2024-02-12,0.6113279389791146
Journal of Organic Chemistry,"General Route to 4a-Methylhydrofluorene Diterpenoids:  Total Syntheses of (±)-Taiwaniaquinones D and H, (±)-Taiwaniaquinol B, (±)-Dichroanal B, and (±)-Dichroanone","A general and convergent route for the synthesis of the 4a-methylhydrofluorene diterpenoids has been established through a common hexahydrofluorenone intermediate (10) obtained via Pd(0)-catalyzed reductive cyclization of a substituted 2-(2-bromobenzyl) methylene cyclohexane (13). The strategy has been successfully utilized for the synthesis of (+/-)-taiwaniaquinones D (3) and H (5), (+/-)-taiwaniaquinol B (1), (+/-)-dichroanal B (7), and (+/-)-dichroanone (8).",10.1021/jo052589w,2006-03-10,0.61131584302551
Organic Letters,Total Synthesis of Luotonin A and Rutaecarpine from an Aldimine via the Designed Cyclization,"The total synthesis of rutaecarpine (1) and luotonin A (2) is described through controlled cyclization of a common aldimine intermediate 5 derived from ethyl-2-aminocinnamate and quinazolinone-2-carbaldehyde. The cyanide-mediated imino-Stetter reaction of aldimine 5 provided the corresponding indole derivative 3, from which the total synthesis of rutaecarpine (1) was completed via the formation of a 6-membered C-ring. On the other hand, microwave-assisted thermal 6π-electrocyclization of the common intermediate 5, followed by the formation of a 5-membered C'-ring, allowed the completion of the total synthesis of luotonin A (2).",10.1021/acs.orglett.6b02597,2016-10-04,0.6112965470033365
Journal of the American Chemical Society,Total Synthesis of Apoptolidin:  Construction of Enantiomerically Pure Fragments,"A general strategy for the total synthesis of the antitumor agent apoptolidin (1) is proposed, and the chemical synthesis of the defined key building blocks (4, 5, 6, 8, and 9) in their enantiomerically pure forms is described. The projected total synthesis calls for a dithiane coupling reaction to construct the C(20)-C(21) bond, a Stille coupling reaction to form the C(11)-C(12) bond, and a Yamaguchi macrolactonization to assemble the macrolide ring, as well as two glycosidation reactions to fuse the carbohydrate units onto the molecule. First and second generation syntheses to the required fragments for apoptolidin (1) are described.",10.1021/ja0304953,2003-11-21,0.6112858650879242
Organic Letters,Asymmetric Total Synthesis of TAN-1085 Facilitated by Pd-Catalyzed Atroposelective C–H Olefination,"Asymmetric total synthesis of TAN-1085 via Pd-catalyzed atroposelective C-H olefination is described. This synthesis features the gram-scale construction of axially chiral biaryls in an enantiopure form employing the readily available l -tert-leucine as the chiral transient auxiliary. The synthetic approach might provide a unified strategy for the total synthesis of natural products containing trans-9,10-dihydrophenanthrene-9,10-diol motifs.",10.1021/acs.orglett.9b01099,2019-04-22,0.6112770147310091
Organic Letters,"Synthesis of (−)-6,7-Dideoxysqualestatin H5 by Carbonyl Ylide Cycloaddition–Rearrangement and Cross-electrophile Coupling","High Resolution Image Download MS PowerPoint Slide An asymmetric synthesis of (−)-6,7-dideoxysqualestatin H5 is reported. Key features of the synthesis include the following: (1) highly diastereoselective n -alkylation of a tartrate acetonide enolate and subsequent oxidation–hydrolysis to provide an asymmetric entry to a β-hydroxy-α-ketoester motif; (2) facilitation of Rh(II)-catalyzed cyclic carbonyl ylide formation–cycloaddition by co-generation of keto and diazo functionality through ozonolysis of an unsaturated hydrazone; and (3) stereoretentive Ni-catalyzed Csp 3 –Csp 2 cross-electrophile coupling between tricarboxylate core and unsaturated side chain to complete the natural product.",10.1021/acs.orglett.7b01513,2017-06-20,0.6112660365540618
Organic Letters,Asymmetric Total Syntheses of Aetheramides and Their Stereoisomers: Stereochemical Assignment of Aetheramides,"The concise total syntheses of the potent HIV inhibitors aetheramides A and B (IC50 values of 15 and 18 nM), as well as three pairs of their stereoisomers, were achieved, which allowed the complete stereochemical assignment of aetheramides for the first time. With a longest linear sequence of 15 steps, the convergent, fully stereocontrolled route provided aetheramides A and B in 5.3% and 3.6% yields, respectively. The synthetic strategy features efficient Stille coupling for macrocyclization, asymmetric aldol reactions to establish the ambiguous stereochemistries at C-17 and C-26, and implementation of mild conditions to avoid the epimerization of the sensitive polyketide moiety and the migration of the labile lactone.",10.1021/acs.orglett.6b02371,2016-09-07,0.6112622881588924
Organic Letters,Approach to Merosesquiterpenes via Lewis Acid Catalyzed Nazarov-Type Cyclization: Total Synthesis of Akaol A,"A Lewis acid catalyzed Nazarov-type cyclization of arylvinylcarbinol has been developed for the asymmetric synthesis of carbotetracyclic core of merosesquiterpenes. The reaction works only in the presence of 2 mol % of Sn(OTf)2 and Bi(OTf)3 in dichloroethane under elevated temperature. The methodology offers the synthesis of a variety of enantioenriched arylvinylcarbinols from commercially available (3aR)-sclareolide 9 in six steps with an eventual concise total synthesis of marine sesquiterpene quinol, akaol A (1a).",10.1021/acs.orglett.6b00446,2016-03-30,0.6112596490343163
Synlett,Synthesis of New Glycosylated Porphyrin Derivatives with a Hydrocarbon Spacer Arm,All articles of this category New mono-glycosylated porphyrins possessing a glycosyl or ribosyl side chain were obtained in four steps. The synthetic route presented here shows wide applicability for the preparation of many mono-glycosylated tristolylporphyrin derivatives.,10.1055/s-1993-22529,1993-01-01,0.6112568562990238
Tetrahedron,An efficient synthesis of 3-vinylpyrroles by Stille coupling reaction of 3-iodopyrroles with vinyltributyltin,,10.1016/0040-4039(95)01459-u,1995-09-01,0.6112563289885372
Journal of the American Chemical Society,The First Total Synthesis of (±)-Ingenol,"The first total synthesis of (+/-)-ingenol has been achieved. The key features of the synthesis include the use of a highly diastereoselective Michael reaction to fix the C-11 methyl stereochemistry and the incorporation of the dimethylcyclopropane via diastereoselective carbene addition to the Delta13,14 olefin. The intramolecular dioxenone photoaddition-fragmentation sequence leads to the establishment of the critical C-8/C-10 trans intrabridgehead stereochemistry, a central challenge in the synthesis of ingenanes. The completion of the synthesis proceeds using the C-6alpha hydroxymethyl group as the sole handle for oxidation of seven contiguous carbon centers.",10.1021/ja026600a,2002-07-31,0.6112524342016985
Organic Letters,Stereocontrolled Total Synthesis of Hedyotol A,"The total synthesis of hedyotol A (1), a natural product isolated from Hedyotis lawsoniae (DC.) Wight et Arn. (Rubiaceae), was accomplished in a highly stereocontrolled manner. Key steps include an L-proline-catalyzed cross-aldol reaction and the biomimetic construction of a furofuran lignan skeleton through a quinomethide intermediate.",10.1021/ol500524y,2014-03-24,0.6112438379813204
Tetrahedron,"A simple route to the 7-cyclopenta[a]pentalene system: preparation of the 1,2,3,4,5,6-hexachloro-derivative.",,10.1016/s0040-4039(01)81327-7,1984-01-01,0.6112430079786589
Synthesis,Synthesis of a Bifunctional Monophosphinate DOTA Derivative Having a Free Carboxylate Group in the Phosphorus Side Chain,"A new bifunctional cyclen-based ligand, 3-[hydroxy({4,7,10-tris[(tert-butoxycarbonyl)methyl]-1,4,7,10-tetraazacyclododecan-1-yl}methyl)phosphoryl]propanoic acid, was synthe-sized by alkylation of tri-tert-butyl 1,4,7,10-tetraazacyclododecane-1,4,7-triacetate (t-Bu3DO3A) by ethyl 3-{ethoxy[(mesyloxy)methyl]phosphoryl}propanoate [MsOCH2P(O)(OEt)CH2CH2CO2Et]. The ethyl carboxylate group in the side chain was selectively deprotected to obtain the esterified bifunctional ligand. More efficient syntheses of some phosphinopropanoic acid derivatives were devised and the phosphorus alkylation reagent was prepared starting from hypophosphorus acid or its salt.",10.1055/s-2008-1072571,2008-04-25,0.6112390869006471
Tetrahedron,Synthesis of enantiomerically pure functionalised amides (EPC-synthesis) from chiral β-aminated organolithium intermediates,,10.1016/s0040-4039(00)76980-2,1994-07-01,0.6112318735064262
Tetrahedron,A highly convergent synthesis of the phytoalexin elicitor hexasaccharide,,10.1016/s0040-4039(98)00087-2,1998-04-01,0.611231478662506
Reaction Chemistry & Engineering,An improved stereodivergent and practical synthesis of α- and β-pseudouridines,A simplified stereodivergent and concise route featuring non-cryogenic conditions enable access to both anomers of pseudouridine.,10.1039/d2re00381c,2022-12-08,0.6112269665447733
Journal of Organic Chemistry,Efficient One-Pot Synthesis of the 2-Aminocarbonylpyrrolidin-4-ylthio-Containing Side Chain of the New Broad-Spectrum Carbapenem Antibiotic Ertapenem,"An efficient synthesis of the 2-aminocarbonylpyrrolidin-4-ylthio containing side chain of ertapenem (MK-0826) is described. Starting material N-(O,O-diisopropyl phosphoryl)-trans-4-hydroxy-L-proline is converted in a one-pot process to (2S)-cis-3-[[(4-mercapto-2-pyrrolidinyl)carbonyl]amino]benzoic acid monohydrochloride in 70-75% overall yield via a series of six reactions. The development of each of these reactions and the isolation of the product is discussed in detail.",10.1021/jo011170c,2002-06-01,0.6112174156024087
Tetrahedron,Ring expansion: formal total synthesis of (−)-paroxetine,,10.1016/s0040-4039(01)01096-6,2001-08-01,0.6112133710199897
Tetrahedron,Bridged to fused ring interchange. The total synthesis of (±)-ledol,,10.1016/0040-4039(95)02336-4,1996-02-01,0.6112133710199897
Organic Letters,Studies on the Total Synthesis of RP 66453:  Synthesis of Fully Functionalized 15-Membered Biaryl-Containing Macrocycle,"[structure: see text] Palladium-catalyzed Suzuki cross-coupling, Corey's enantioselective alkylation of glycine template, and macrolactamization are key steps in an efficient synthesis of the 15-membered macrocycle 2.",10.1021/ol016021v,2001-05-24,0.6112068747442704
Journal of Organic Chemistry,Stereoselective Total Synthesis of (±)-Peribysin E,"Radical cyclization of iodoketone 3 afforded cis-hydrindanone 8. Compound 8 was converted into key intermediate 5 via conventional transformations. Annulation of a spiro-lactal unit to 5 was pursued with three different approaches. In the first approach, radical cyclization of propargyl ester 17 provided spiro-lactone 18 with an undesired stereochemistry. Attempts to invert the stereochemistry at the spiro-center via retro-aldol and aldol condensation of compound 20 failed. In the second approach, key intermediate 5 was transformed into 23. Acylation of compound 23 gave 24 as a single diastereomer with the desired stereochemistry but in low yield. NBS bromination of 24 followed by lactone formation gave 26 in low yield. Alternatively, allylic oxidation of 24 with SeO(2) followed by lactonization gave 26 also in low yield. Finally, a third approach employing a semipinacol-type rearrangement of epoxy-alcohol 33 gave aldehyde 34 with the desired stereochemistry. Treatment of compound 34 with HCl in MeOH effected spiro-lactal formation and provided (±)-peribysin E. The overall yield of our synthesis is 3.2% from 2-methylcyclohenen-1-one.",10.1021/jo2021604,2011-11-17,0.6111961491037865
Synthesis,A Simple and Efficient Synthesis of the Antimigraine Drug Lomerizine,"The synthesis of the antimigraine drug 1-[bis(4-fluorophenyl)methyl]-4-(2,3,4-trimethoxybenzyl)piperazine has been carried out in very good yields. The five-step synthesis started from bis(4-fluorophenyl)methanone. This route can be applied for large-scale preparation of lomerizine.",10.1055/s-0029-1218749,2010-04-19,0.6111895943563358
Organic Letters,Total Synthesis of (−)-Aspidospermidine via an Enantioselective Palladium-Catalyzed Allylic Substitution Strategy,"High Resolution Image Download MS PowerPoint Slide A total synthesis of (−)-aspidospermidine via an enantioselective Pd-catalyzed allylic substitution strategy is reported. This represents the first application of a Pd-catalyzed allylic substitution with a 3-substituted indole derivative in the synthesis of Aspidosperma alkaloids. In our synthetic route, the allylic substitution reaction was the stereo defining step. The pentacyclic framework was then constructed in a fully diastereoselective sequence. This culminated in the shortest enantioselective synthesis of aspidospermidine reported to date, in seven linear steps.",10.1021/acs.orglett.4c03445,2024-10-31,0.6111782674549695
Organic Process Research & Development,Development of an Efficient Synthesis for a Nipecotate-Containing Immunopotentiator,The preparation of Elanco Animal Health immunopotentiator ( S )-ethyl-1-(2-thiopheneacetyl)-3-piperidinecarboxylate ( 1 ) is described. The synthesis includes a new resolution of racemic ethyl nipecotate with dibenzoyl- l -tartaric acid. The resolved salt is found to couple directly with commercially available 2-thiopheneacetyl chloride under environmentally friendly Schotten−Baumann conditions to afford the amide in high yield. The final product is an oil which is purified by wiped film evaporative distillation.,10.1021/op049941c,2004-06-05,0.6111636841207334
Journal of Organic Chemistry,"Efficient Synthesis and Characterization of Dibenzo[<i>a</i>,<i>m</i>]rubicenes and Tetrabenzo[<i>a</i>,<i>f</i>,<i>r</i>,<i>m</i>]rubicenes","We report an efficient synthesis of dibenzo[a,m]rubicenes and tetrabenzo[a,f,r,m]rubicenes involving ICl-mediated benzannulation of 1,4-diphenyl-2,5-dialkynylbenzene 5 as the key step. Preliminary data on the photophysical properties of these new indeno-PAHs are reported.",10.1021/jo9015437,2009-10-02,0.611163491961989
Angewandte Chemie International Edition,Total Synthesis of (±)‐Aspidophylline A,"A total synthesis of aspidophylline A, a pentacyclic akuammiline-type monoterpene indole alkaloid, is described. The synthesis features: 1) rapid access to a fully functionalized dihydrocarbazole through the desymmetrization of readily available 2-allyl-2-(o-nitrophenyl)cyclohexane-1,3-dione; 2) an intramolecular azidoalkoxylation of an enecarbamate to install both the furoindoline ring and the azido functionality; and 3) an intramolecular Michael addition for the construction of the 2-azabicyclo[3.3.1]nonane ring system.",10.1002/anie.201310929,2014-01-22,0.6111493406433568
Tetrahedron,"Enantioselective synthesis of phomallenic acid C, an inhibitor of FAS II pathway",,10.1016/j.tetlet.2008.06.035,2008-06-13,0.611126962927423
Journal of the American Chemical Society,Fully Convergent Chemical Synthesis of Ester Insulin: Determination of the High Resolution X-ray Structure by Racemic Protein Crystallography,"Efficient total synthesis of insulin is important to enable the application of medicinal chemistry to the optimization of the properties of this important protein molecule. Recently we described ""ester insulin""--a novel form of insulin in which the function of the 35 residue C-peptide of proinsulin is replaced by a single covalent bond--as a key intermediate for the efficient total synthesis of insulin. Here we describe a fully convergent synthetic route to the ester insulin molecule from three unprotected peptide segments of approximately equal size. The synthetic ester insulin polypeptide chain folded much more rapidly than proinsulin, and at physiological pH. Both the D-protein and L-protein enantiomers of monomeric DKP ester insulin (i.e., [Asp(B10), Lys(B28), Pro(B29)]ester insulin) were prepared by total chemical synthesis. The atomic structure of the synthetic ester insulin molecule was determined by racemic protein X-ray crystallography to a resolution of 1.6 Å. Diffraction quality crystals were readily obtained from the racemic mixture of {D-DKP ester insulin + L-DKP ester insulin}, whereas crystals were not obtained from the L-ester insulin alone even after extensive trials. Both the D-protein and L-protein enantiomers of monomeric DKP ester insulin were assayed for receptor binding and in diabetic rats, before and after conversion by saponification to the corresponding DKP insulin enantiomers. L-DKP ester insulin bound weakly to the insulin receptor, while synthetic L-DKP insulin derived from the L-DKP ester insulin intermediate was fully active in binding to the insulin receptor. The D- and L-DKP ester insulins and D-DKP insulin were inactive in lowering blood glucose in diabetic rats, while synthetic L-DKP insulin was fully active in this biological assay. The structural basis of the lack of biological activity of ester insulin is discussed.",10.1021/ja311408y,2013-01-23,0.6111252421960084
Tetrahedron,Synthetic study of tetramethyljulolidine—a key intermediate toward the synthesis of the red dopant DCJTB for OLED applications,,10.1016/s0040-4039(02)02506-6,2003-01-01,0.6111212500561725
Synthesis,"A New and Practical Synthesis of Cariprazine through the Facile Construction of 2-[trans-4-(3,3-Dimethylureido)cyclohexyl]acetic Acid","A new, practical, and improved synthetic route to cariprazine is described. The key step is the facile preparation of 2-[4-(3,3-dimethylureido)cyclohexyl]acetic acid in the trans configuration through direct recrystallization. The entire synthetic procedure was accomplished under mild conditions while avoiding tedious purification processes. The trans configuration of cariprazine was confirmed by X-ray crystallographic analysis.",10.1055/s-0035-1561865,2016-06-23,0.6111173886708665
Journal of Organic Chemistry,Enantioselective Formal Synthesis of (+)-Dihydrocorynantheine and (−)-Dihydrocorynantheol,"The enantioselective construction of the 3-ethylindolo[2,3-a]quinolizidine moiety present in numerous indole alkaloids is reported, the key steps being a stereoselective cyclocondensation of (S)-tryptophanol with an appropriate racemic delta-oxoester and a regio- and stereoselective cyclization of the resulting oxazolopiperidones on the lactam carbonyl group. A new procedure for the removal of the hydroxymethyl auxiliary group, involving oxidation to an aldehyde, dehydration of the corresponding oxime, and reductive decyanation of the resulting alpha-aminonitrile, has been developed. The preparation of indoloquinolizidine 27 represents a formal total synthesis of (+)-dihydrocorynantheine, (-)-dihydrocorynantheol, and other indolo[2,3-a]quinolizidine and oxindole alkaloids bearing the same substitution pattern.",10.1021/jo802387c,2008-12-15,0.6111043970220472
Organic Letters,Total Synthesis of (−)-3-Oxoisotaxodione,"The first total synthesis of the abietaquinone methide diterpenoid (−)-3-oxoisotaxodione is reported. The key enabling step is the use of a chiral bicyclic hydrazide as an organocatalyst for the enantioselective polyene cyclization of a ( Z )-polyene substrate to form the cis -decalin core of the natural product. The α-oxo- para -quinone methide unit is formed by a two-step oxidation from a phenol, enabling an efficient synthesis of the natural product.",10.1021/acs.orglett.2c00444,2022-03-21,0.6111026861395009
Synthesis,Formation of Two 4-Imidazolylmethylphosphonium Salts and their Synthetic Studies Toward Histamine H<sub>3</sub>-Ligands,"A simple and convenient preparation of {[1H-imidazol-4(5)-yl]methyl}triphenylphosphonium chloride (5) is described. The phosphonium salt 5 could be applied to the synthesis of 1-[1H-imidazol-4(5)-yl]-5-arylpentan- or 6-arylhexan-3-ones 4a-d exhibiting histamine H3-antagonistic activities via a 1,3-diazafulvene intermediate 6 generated from 5. Further, two-methylene-enlongated homolog 3 of imifuramine was efficiently synthesized, starting from Wittig olefination of aldehyde 24 using [(1-tritylimidazol-4-yl)methyl]triphenylphosphonium chloride 7.",10.1055/s-2003-42442,2003-01-01,0.6111012121597427
Organic Process Research & Development,Selective Metalation of Functionalized Quinazolines to Enable Discovery and Advancement of Covalent KRAS Inhibitors,"The quinazoline compound ARS-1620 is a recently discovered, mutant-specific covalent inhibitor of KRAS G12C . Route scouting in support of multigram ARS-1620 batches led to a new synthetic approach that relies on metalation of substituted quinazolines at C7. The exquisite selectivity seen in this metalation formed the basis for a scalable route to kilogram quantities of compounds in this family. It also accelerated medicinal chemistry efforts as critical intermediates became readily available in large quantities.",10.1021/acs.oprd.2c00242,2022-10-13,0.6110979845804152
Journal of Organic Chemistry,One-Pot Synthesis of Core Structure of Shewanelline C Using an Azidoindoline,"The unprecedented synthesis of the indolines bearing N3-quinazolin-2,4-dione moiety using an AZIN is reported. The concise synthesis features the tandem Staudinger/chemo-selective aza-Wittig/cyclization sequence of AZINs with isatoic anhydride by a one-pot protocol.",10.1021/acs.joc.3c00013,2023-03-08,0.6110943529713133
Journal of Organic Chemistry,"Total Synthesis of Diterpenoid Quinone Methide Tumor Inhibitor, (+)-Taxodione","An asymmetric polyene cyclization (92% ee ) strategy has been successfully applied for the first asymmetric total synthesis of oxidized abietane, anticancer agent, taxodione ( 1 ) sharing a trans -decalin system. Additionally, the total syntheses of pomiferin B ( 2 ) and gaultheric acid ( 3 ) (a nor -abietane) were achieved utilizing this unified approach.",10.1021/acs.joc.3c02541,2024-01-16,0.6110907084804668
Synthesis,Synthesis of N-(Hetero)arylconvolvine Derivatives through a Palladium-Catalyzed Buchwald–Hartwig Cross-Coupling,"The present study describes the isolation of convolvine from the roots of the Tunisian plant Convolvulus dorycnium L. and its synthesis through a four-step sequence starting from tropine. Then, an efficient synthesis of N-(het)aryltropanes derivatives by a sequence of a palladium-catalyzed N-arylationof convolvine has been established. This strategy enabled access to unknown tropane scaffolds of biological interests.",10.1055/s-0039-1690238,2019-11-05,0.6110883345655338
Synthesis,Pyrroles and Indolizidines from Deprotonated α-(Alkylideneamino)nitriles,"Their ready availability from simple starting materials in only two synthetic steps and their versatility as building blocks for the construction of highly substituted amines and N-heterocycles renders α-(alkylideneamino)nitriles useful synthetic intermediates. Herein, short syntheses of tri- and tetrasubstituted pyrroles including the northern half of the HMG-CoA reductase inhibitor atorvastatin as well as an access to 3-substituted indolizidines will be described.",10.1055/s-0030-1260415,2011-04-29,0.6110835778461481
Synlett,Four-Step Route to Novel Bisflavylium Dications - First Synthesis of Phloroglucinol-Type Derivatives,Various bisflavylium dications have been prepared in an efficient four-step manner utilizing the acid-mediated condensation between bis(arylethynylketones) and activated phenols as the key step. Of special note is that phloroglucinol-type bisflavylium salts have been obtained for the first time thanks to this procedure.,10.1055/s-0032-1316681,2012-08-08,0.6110831499712364
Tetrahedron,Synthesis of a new carbapenem with a 6-methyl hydroxyacetate side chain,,10.1016/s0040-4039(01)80988-6,1987-01-01,0.6110766605035114
Journal of Organic Chemistry,Total Synthesis of Enantiopure Chabrolonaphthoquinone B Via a Stereoselective Julia-Kocienski Olefination,"The total synthesis of cytotoxic meroditerpenoid naphthoquinone derivative chabrolonaphthoquinone B ( 1 ) in an enantiospecific manner is divulged using a chiral pool approach. The key step of our synthetic route is a modified Julia olefination between a sulfone-bearing aliphatic fragment and a Diels–Alder-derived aromatic aldehyde, leading to the stereoselective construction of the E -trisubstituted double bond.",10.1021/acs.joc.1c01106,2021-07-12,0.6110765969329764
Synthesis,The Stereoselective Total Synthesis of (+)-Stagonolide B,"The stereoselective total synthesis of the nonenolide, (+)-stagonolide B is described. The key steps involve epoxide homologation, hydrolytic kinetic resolution and ring-closing metathesis.",10.1055/s-0029-1218638,2010-01-08,0.6110717478340875
Organic Letters,Asymmetric Synthesis of Actinoidic Acid Derivatives,"Synthesis of fully protected actinoidic acid derivative 3 and selectively protected biaryl bisamino acid 4, intermediates for vancomycin total synthesis, are reported.",10.1021/ol006110s,2000-07-12,0.6110665912002318
Journal of Organic Chemistry,"Asymmetric Syntheses of (+)-Preussin B, the C(2)-Epimer of (−)-Preussin B, and 3-Deoxy-(+)-preussin B","Efficient de novo asymmetric syntheses of (+)-preussin B, the C(2)-epimer of (-)-preussin B, and 3-deoxy-(+)-preussin B have been developed, using the diastereoselective conjugate addition of lithium (S)-N-benzyl-N-(α-methylbenzyl)amide to tert-butyl 4-phenylbut-2-enoate and diastereoselective reductive cyclizations of γ-amino ketones as the key steps to set the stereochemistry. Conjugate addition followed by enolate protonation generated the corresponding β-amino ester. Homologation using the ester functionality as a synthetic handle gave the corresponding γ-amino ketone. Hydrogenolytic N-debenzylation was accompanied by diastereoselective reductive cyclization in situ; reductive N-methylation then gave 3-deoxy-(+)-preussin B as the major diastereoisomeric product. Meanwhile, the same conjugate addition but followed by enolate oxidation with (+)-camphorsulfonyloxaziridine gave the corresponding anti-α-hydroxy-β-amino ester. α-Epimerization by oxidation and diastereoselective reduction then gave access to the corresponding syn-α-hydroxy-β-amino ester. Homologation of both of these diastereoisomeric α-hydroxy-β-amino esters gave the corresponding β-hydroxy-γ-amino ketones. N-Debenzylation and concomitant diastereoselective reductive cyclization, followed by reductive N-methylation, provided the C(2)-epimer of (-)-preussin B and (+)-preussin B as the major diastereoisomeric products, respectively. The overall yields (from phenylacetaldehyde) were 19% for 3-deoxy-(+)-preussin B over seven steps, 8% for the C(2)-epimer of (-)-preussin B over nine steps, and 7% for (+)-preussin B over eleven steps.",10.1021/acs.joc.6b00362,2016-04-14,0.6110643059974322
Organic Letters,"A Flexible and Divergent Strategy to Flavonoids with a Chiral A-Ring Featuring Intramolecular Michael Addition: Stereoselective Synthesis of (+)-Cryptocaryone, (+)-Cryptogione F, and (+)-Cryptocaryanones A and B, as Well as (+)-Cryptochinones A and C","A flexible strategy has been developed to synthesize divergent flavonoids bearing a chiral A-ring. As two key steps, the coupling via a boron-mediated aldol condensation and the cyclization via a highly stereoselective intramolecular Michael addition of 1,3-diketone proceed under mild conditions; thus, the chiral flavonoids bearing C-7 oxy functional groups or olefinic bonds are both easily accessible. Using this approach, the first synthesis of (+)-cryptogione F, (+)-cryptocaryanone B, and (+)-cryptochinones A and C, as well as stereoselective synthesis of (+)-cryptocaryone and (+)-cryptocaryanone A, were achieved from 2-deoxy-d-ribose in high overall yields.",10.1021/acs.orglett.8b00479,2018-03-19,0.6110604660478481
Organic Letters,Concerning the Synthesis of the Tedanolide C(13)−C(23) Fragment via Anti-Aldol Reaction,"Synthesis of C(13)-C(23) aldehyde 4, an important intermediate in a planned total synthesis of tedanolide, is described. The stereoselectivity of the key anti-aldol reaction of aldehyde 5 and ketone 6 (en route to 4) perfectly tracks the enantiomeric purity of 5. It is demonstrated that aldehyde 24, a precursor of 5, undergoes facile epimerization during a Swern oxidation and stabilized ylide olefination sequence.",10.1021/ol800546g,2008-04-19,0.6110588932336686
Organic Letters,Formal Total Synthesis of Echinopines A and B via Cr(0)-Promoted [6π + 2π] Cycloaddition,"A concise formal synthesis of echinopines A and B is reported. The key [5.5.7] tricyclic intermediate, which has been previously used for the synthesis of echinopine A and B, was assembled using Cr(0)-promoted photochemical [6π + 2π] cycloaddition followed by a radical cyclization step.",10.1021/acs.orglett.5b01326,2015-06-12,0.611040349722005
Tetrahedron,"Syntheses of new humulene derivatives; (2E,6E,9E)- and (2Z,6E,9E)-cycloundecatrienones, by intramolecular alkylation of protected cyanohydrin. A route to humulene",,10.1016/s0040-4039(00)86230-9,1983-01-01,0.6110396419249382
Organic Letters,Rh/DuanPhos-Catalyzed Asymmetric Hydrogenation of β-Acetylamino Vinylsulfides: An Approach to Chiral β-Acetylamino Sulfides,"Rh/DuanPhos-catalyzed asymmetric hydrogenation of challenging β-acetylamino vinylsulfides has been developed, affording chiral β-acetylamino sulfides with high yields and excellent ee's (up to 99% ee). This novel methodology provides an efficient and concise synthetic route to chiral β-acetylamino sulfides. The potential utility of this protocol in the synthesis of Apremilast has also been disclosed.",10.1021/acs.orglett.7b01115,2017-05-11,0.6110392166944986
Synlett,Development of a Triethylborane-Mediated Giese Cyclization/Aldol Reaction Cascade for the Total Synthesis of Ganoapplanin,"Abstract We present our synthetic endeavors towards the Ganoderma meroterpenoid ganoapplanin. This natural product was isolated from a Ganoderma fungus in 2016 and was found to be an inhibitor for T-type voltage-gated calcium channels. Our synthetic approach is based on a powerful intramolecular Giese cyclization/intermolecular aldol cascade to link the northern aromatic to the southern terpenoid fragment. This article highlights the synthetic studies that ultimately led to the successful development of the key cascade reaction, culminating in the first total synthesis of ganoapplanin. 1 Introduction 2 Synthesis of the Southern Terpenoid Fragment 3 Synthesis of the Northern Terpenoid Fragment 4 Triethylborane-Mediated Giese Cyclization/Aldol Reaction Cascades 5 Completion of the Total Synthesis of Ganoapplanin 6 Conclusion",10.1055/a-2501-4079,2024-12-12,0.6110380509339172
Journal of Organic Chemistry,"Total Synthesis of (±)-13-Methoxy-15-oxozoapatlin, a Rearranged Kaurane Diterpenoid",A 21-step linear synthesis of the structurally novel and biologically intriguing diterpenoid (+/-)-13-methoxy-15-oxozoapatlin (6) is described. Of particular note in this work is the development of a new method for the construction of the functionalized bicyclo[3.2.1]octane unit present in the target substance.,10.1021/jo030389j,2004-04-01,0.6110367239651179
Organic Letters,Concise and Enantioselective Synthesis of the Aminocyclitol Core of Hygromycin A,"[reaction: see text] Stereoselective aminohydroxylation and dihydroxylation using osmium(VIII) oxidants enabled the short and efficient synthesis of the aminocyclitol core of hygromycin A. In addition to allowing the selective introduction of the heteroatoms N and O, the use of osmium (via an osmate ester) as a protecting group for a 1,2-glycol is also reported. This tactic allowed efficient differentiation of otherwise equivalent hydroxyl groups and allowed us to complete the synthesis in short order (14 steps) and excellent overall yield (12%).",10.1021/ol0473750,2005-03-01,0.6110343896137785
Organic Process Research & Development,Large-Scale Synthesis of (<i>R</i>)-2-Amino-1-(2-furyl)ethanol via a Chemoenzymatic Approach,A two-step chemoenzymatic synthesis of ( R )-2-amino-1-(2-furyl)ethanol for laboratory production was developed followed by successful up-scaling to kilogram scale. The generation of the asymmetric centre was accomplished by a highly enantioselective cyanohydrin reaction of furan-2-carbaldehyde with hydrocyanic acid catalyzed by the hydroxynitrile lyase from Hevea brasiliensis . Subsequent sodium borohydride reduction furnished the desired product with an enantiomeric excess of higher than 99.5%. This procedure can be considered a convenient general route for the stereoselective synthesis of ethanol amine derivatives underlining the role of biocatalysis for the generation of stereogenic centres in the synthesis of chiral intermediates.,10.1021/op050264b,2006-03-30,0.6110285251216252
Angewandte Chemie International Edition,Rapid Access to Orthogonally Functionalized Naphthalenes: Application to the Total Synthesis of the Anticancer Agent Chartarin,"We report the synthesis of orthogonally functionalized naphthalenes from simple, commercially available indanones in four steps. The developed method proceeds through a two-step process that features a thermally induced fragmentation of a cyclopropane indanone with simultaneous 1,2-chloride shift. Migration of the chloride substituent occurs in a regioselective manner to preferentially afford the para-chloronaphthol substitution pattern. The obtained naphthols are versatile building blocks that can be selectively modified and used for the efficient construction of biologically active molecules. This has enabled the total synthesis of the potent anticancer natural product chartarin through a highly convergent retrosynthetic bond disconnection.",10.1002/anie.201605071,2016-06-29,0.6110271783402264
Synthesis,Late-Stage Two-Step C11–H Arylation of Dibenzooxa/thiazepines,"Abstract A practical and efficient synthesis of 11-aryldibenzooxa/thiazepines is achieved, via a late-stage and two-step C11–H arylation of simple dibenzooxa/thiazepines. The adoption of Grignard addition and DDQ dehydrogenation allows for operationally simple and chemically reliable, step-efficient, and high-yielding transformations. The two-step and one-pot procedures provide excellent yields. The gram-scale experiment demonstrates the promising synthetic potentials in large-scale applications, and the advantages of this method are also highlighted in the efficient synthesis of an H460TaxR inhibitor.",10.1055/a-2038-2323,2023-02-17,0.6110248312249617
Synlett,Preparation of 2-Azabicyclo[2.1.1]hexane Hydrochloride,"A batchwise, multigram preparation of 2-azabicyclo-[2.1.1]hexane hydrochloride ( 1 ·HCl) was developed, delivering a total of 195 grams of material. The key synthetic step involves an intramolecular displacement of a primary alkyl chloride with a tert -butylsulfinamide to forge the [2.1.1]-bicyclic ring system.",10.1055/s-0035-1562380,2016-07-07,0.6110247999211562
Organic Letters,Total Synthesis of Mersicarpine through a Cationic Cyclization Approach,A concise total synthesis of mersicarpine is achieved by exploiting a cyclic carbamate for generation of a tertiary carbocation. The key step involves intramolecular Friedel-Crafts alkylation with this carbocation for the construction of a quaternary carbon center and a subsequent oxidation and cyclization cascade for the formation of a seven-membered cyclic imine. The chemistry allowed for a rapid one-pot synthesis of mersicarpine from a simple intermediate using straightforward chemical operations.,10.1021/ol500308e,2014-02-20,0.6110245997726395
Journal of Organic Chemistry,Synthetic Studies toward the Total Synthesis of Tautomycetin,"The studies culminating in the synthesis of two large subunits of tautomycetin are described. The first one, fragment C1–C12 that has an anti -1,3-dimethyl system and a terminal diene unit, was accomplished in 10 linear steps in 7.4% overall yield. The second one, fragment C13–C25 which bears the sensitive anhydride framework and the majority of the stereogenic centers, was prepared in 13 linear steps (longest sequence) in 8% overall yield. Among the key transformations used, a regioselective epoxide opening, a Pd-catalyzed addition of terminal alkyne to acceptor alkyne, a Mukaiyama aldol reaction, a Yamaguchi esterification, and a homemade mild di-esterification can be cited. The chosen strategies allowed good yields, stereoselectivity, reproducibility, and scalability for several important intermediates.",10.1021/acs.joc.9b01712,2019-09-04,0.6110185824338387
Organic Letters,Total Synthesis of Zincophorin Methyl Ester,"[reaction: see text]. A convergent total synthesis of the methyl ester of zincophorin, an ionophore antibiotic, has been realized relying on a diastereoselective titanium-mediated aldol coupling between the C1-C12 and C13-C25 subunits. The latter fragment was prepared by using a Carroll-Claisen rearrangement.",10.1021/ol035177n,2003-10-01,0.611016331999676
Journal of Organic Chemistry,NIS–PPh<sub>3</sub>: A Selective Reagent for the Spiroannulation of <i>o</i>-Allyl Phenols. Total Synthesis of Corallidictyal D,Treatment of o-allyl phenols with catalytic NIS-PPh3 affords the corresponding spirodihydrobenzofuran derivatives in high yield with high regio- and total stereoselectivity under mild conditions. These results were utilized to achieve the first total synthesis of the protein kinase C inhibitor corallidictyal D starting from α-ionone.,10.1021/jo4014047,2013-08-28,0.6110161273974724
Organic Letters,Studies toward the Total Synthesis of Sorangiolides and Their Analogues. A Convergent Stereoselective Synthesis of the Macrocyclic Lactone Precursors,"Stereoselective synthesis of the fully protected 18-membered macrocyclic lactones as the immediate precursors of the natural products, sorangiolides A and B, is described. The key steps used in the synthesis include the sp3-hybridized carbon-carbon Fu cross coupling, the stereoselective Evans' aldol reaction with 1,5-anti induction, the 1,3-diastereoselective syn reduction of a beta-hydroxyketone intermediate, and Mukaiyama macrolactonization reactions.",10.1021/ol070517g,2007-05-16,0.6110135561382095
Synlett,Total Synthesis of the Squalene Synthase Inhibitor Zaragozic Acid C,"All articles of this category The total synthesis of zaragozic acid C has been achieved by a convergent strategy, wherein the key feature of the construction of 2,8-dioxabicyclo[3.2.1]octane core structure is a simultaneous creation of the C4 and C5 quaternary carbon centers by Sn(OTf) 2 -promoted aldol coupling reaction between α-keto ester and silyl ketene thioacetal derived from L- and D-tartaric acids, respectively. zaragozic acid C - squalene synthase inhibitor - Sn(OTf) 2 -promoted aldol coupling reaction - silyl ketene thioacetal - α-keto ester",10.1055/s-1997-6154,1997-06-01,0.6110113697678274
Journal of the American Chemical Society,Efficient and Practical Synthesis of a Potent Anti-MRSA β-Methylcarbapenem Containing a Releasable Side Chain,"We describe a convergent synthesis of the MRSA β-methyl carbapenem 1, wherein the molecule is assembled from the naphthosultam side chain 2 and the allylic carbonate of the β-Me carbapenem piece 6 . The β-Me stereochemistry of 6 is set up in a novel titanium enolate addition into the TBDMS acetoxy azetidinone 5 . The benzenesulfonate salt of 1 is endowed with exceptional stability.",10.1021/ja992486t,1999-11-24,0.6110109752817056
Tetrahedron,Regioselective synthesis of derivatives of l-idopyranuronic acid: A key constituent of glycosaminoglycans,,10.1016/0040-4039(95)01810-5,1995-11-01,0.6110095388585683
Journal of the American Chemical Society,"Total Synthesis of Halichondrin A, the Missing Member in the Halichondrin Class of Natural Products","A total synthesis of halichondrin A, the phantom member in the halichondrin class of natural products, is reported. The highlights of synthesis include: (1) synthesis of C1-C19 building block 6b via a catalytic asymmetric Cr-mediated coupling of 12 and 13b; (2) synthesis of the right-half of 19 via an asymmetric Ni/Cr-mediated coupling, followed by base-induced furan formation, and Shiina macrolactonization; (3) synthesis of enone 20 via Ni/Cr-mediated coupling of 5 with 19, followed by oxidation; (4) synthesis of halichondrin A from 20, with use of a newly discovered, highly selective TMSOTf-mediated equilibration of C38-epi-halichondrin A to halichondrin A. Two pieces of evidence are presented unambiguously to establish the structure of halichondrin A thus synthesized: one is the synthesis of norhalichondrin A (24) from 19 and 23, and the other is the study of the proton chemical shift difference between synthetic halichondrin A and known members of this class of natural products.",10.1021/ja5013307,2014-03-07,0.610997805903562
Angewandte Chemie International Edition,"Intramolecular Larock Indole Synthesis: Preparation of 3,4‐Fused Tricyclic Indoles and Total Synthesis of Fargesine","Core strength: A new and general strategy for the construction of 3,4-fused tricyclic indoles, which are the core structure of numerous natural products and bioactive molecules, has been developed. The method involves a one-step intramolecular Larock indolization and was successfully applied to the first total synthesis of fargesine.",10.1002/anie.201300571,2013-03-20,0.6109936798992425
Synthesis,An Easy and Convenient Synthesis of 6-Methyl-4(1<i>H</i>)-pyridone-3-carboxylic Acid,"All articles of this category A new and easy synthesis of 6-methyl-4-(1 H )-pyridone-3-carboxylic acid ( 5 ), an important component of broad spectrum cephalosporins, is described. It starts from the readily available ethyl 4-hydroxy-6-methyl-2(1 H )-pyridone-3-carboxylate ( 1 ), which is treated with phosphoryl chloride to give ethyl 2,4-dichloro-6-methylpyridine-3-carboxylate ( 2 ).Selective substitution of the chlorine in 4-position with alkoxide ion leads to the 4-alkoxypyridine derivatives 3 . Hydrogenolysis of 3 affords ethyl 4-alkoxy-6-methyl-pyridine-3-carboxylates 4 ; which are hydrolysed to 5 in one step.",10.1055/s-1988-27614,1988-01-01,0.6109837157124387
Synlett,Enantioselective Synthesis of (-)-Methyl Jasmonate and (+)-Methyl Epijasmonate,"All articles of this category An efficient and flexible enantioselective synthesis of (-)-methyl jasmonate and (+)-methyl epijasmonate, two important phytohormones, is described. The procedure makes use of a chiral cyclopentanoid building block that can easily be prepared from tartaric acid by phosphorus ylide chemistry. methyl jasmonate - methyl epijasmonate - jasmonoides - cyclopentanoids - natural product synthesis",10.1055/s-1997-3213,1997-05-01,0.6109788391685116
Organic Letters,Enantioselective Total Synthesis of (+)-Colletoic Acid via Catalytic Asymmetric Intramolecular Cyclopropanation of an α-Diazo-β-keto Diphenylphosphine Oxide,"The enantioselective total synthesis of (+)-colletoic acid, a potent naturally occurring 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor, is described. This total synthesis features a highly enantioselective catalytic asymmetric intramolecular cyclopropanation of an α-diazo-β-keto diphenylphosphine oxide and five highly stereoselective reactions (cyclopropane opening, Diels-Alder reaction, iodolactonization, alkene formation, and reduction of α,β-unsaturated carboxylic acid).",10.1021/ol303459x,2013-02-11,0.6109743184731007
Synlett,An Efficacious Synthetic Strategy for cis-Clerodane Diterpenoids. Application to the Total Synthesis of (±)-6β-Acetoxy-2-oxokolavenool,All articles of this category An efficient synthetic strategy for cis -clerodane diterpenoids has been developed. The key ingredient is the face selective Diels-Alder reaction of dienophile 8 . The successful application of this strategy has culminated in the total synthesis of the naturally occurring compound 6 β -acetoxy-2-oxokolavenool in racemic form. reductive alkylation - α -cyano ketones - total synthesis - cis -clerodanes,10.1055/s-2001-18105,2001-01-01,0.610965816411488
Angewandte Chemie International Edition,Efficient and Versatile Synthesis of Indoles from Enamines and Imines by Cross‐Dehydrogenative Coupling,Complement for Fischer: An efficient palladium-catalyzed indole synthesis proceeds by the intramolecular cross-dehydrogenative coupling of N-aryl imines under mild conditions using molecular oxygen as the sole oxidant. This practical method relies on anilines and ketones as starting materials (and thus the same retrosynthetic disconnection as the Fischer indole synthesis) and will likely become a popular route.,10.1002/anie.201205079,2012-08-17,0.6109529023137205
Angewandte Chemie International Edition,The Second Total Synthesis of Diazonamide A,"The uniquely woven, highly strained molecular architecture and the potent antitumor activity of diazonamide A (1) make this natural product an attractive synthetic target. The key steps in this total synthesis of 1 include a novel SmI2-induced ring-closing cascade sequence and an unusual oxidation of an indoline to an oxindole in the presence of Pd(OH)2/C.",10.1002/anie.200351112,2003-04-16,0.6109483464077077
Synlett,New Route to Natural Camptothecinthrough Isomünchnone Cycloaddition,A novel approach to camptothecin by [3+2] cycloaddition of an isomünchnone intermediate is described.,10.1055/s-2008-1078205,2008-08-21,0.6109454292512584
Organic Letters,Synthesis of Novel Angular Spirocyclic Azetidines,"The syntheses of a variety of novel angular azaspiro[3.3]heptanes are reported. gem-Difluoro and gem-dimethyl variants of the angular 1,6-diazaspiro[3.3]heptane module were prepared in high yields using efficient sequences. Additionally, a practical one-pot synthesis of 5-oxo-2-azaspiro[3.3]heptanes and subsequent conversions into functionalized derivatives are described. The methods reported are amenable to the synthesis of these building blocks for drug discovery as members of a library or individually on a preparative scale.",10.1021/ol103050c,2011-01-14,0.6109379744787403
Synlett,An Unprecedented Asymmetric Nazarov Cyclization for the Synthesis of Nonracemic Indanes as Endothelin Receptor Antagonists,"All articles of this category An asymmetric synthesis of the novel nonracemic endothelin receptor antagonists, SB 209670 ( 1 a ) and SB 217242 ( 1 b ) is described which utilizes an unprecedented asymmetric Nazarov-type ring closure of the alkylidene-1,3-carbonyl compounds. Excellent 1,5-induction is observed which establishes the required S configuration at the C-3 carbon of an indane skeleton. asymmetric Nazarov cyclization - 1,5-asymmetric induction - endothelin receptor antagonists - indanes",10.1055/s-1999-2912,1999-12-31,0.6109216566972119
Synthesis,Stereoselective Total Synthesis of (+)-Dodoneine,"A total synthesis of the naturally occurring dihydropyranone dodoneine is reported. The combination of a highly catalytic enantioselective allylboration and a highly diastereoselective allylstannation was used for the stereoselective generation of the two stereogenic centers. The pyranone ring was created in two steps through generation of a Z-configured alpha,beta-unsaturated ester and lactonization via intramolecular transesterification.",10.1055/s-0029-1218741,2010-04-19,0.6109175447281033
Synlett,"A Two-Step Synthesis of a Novel 7,8-Dihydro-5,8-ethanoindolizine-6,9(5H)-dione","A two-step synthesis of the novel 5,8-dimethyl-7,8-dihydro-5,8-ethanoindolizine-6,9(5H)-dione from 2,3-dimethyl-1,4-benzoquinone is described. The key step of the synthesis of this unusual fused tricyclic system is the intramolecular regiospecific aza-Michael addition of a pyrrole to an activated double bond by reaction with tetrabutylammonium fluoride under mechanochemical conditions.",10.1055/s-0040-1707182,2020-07-08,0.6109150507111226
Angewandte Chemie International Edition,"A Modular, Efficient, and Stereoselective Synthesis of Substituted Piperidin‐4‐ols","The pied piper-idinol of Hamelin: The one-pot synthesis of piperidin-4-ols by sequential gold-catalyzed cyclization, chemoselective reduction, and spontaneous Ferrier rearrangement has a broad substrate scope and shows excellent diastereoselectivity in the ring-formation step. This chemistry was employed in the six-step enantioselective synthesis of (+)-subcosine II.",10.1002/anie.201004712,2010-10-15,0.610911678645502
Angewandte Chemie International Edition,Total Synthesis of the Tremorgenic Indole Diterpene Paspalinine,Succinct and stereoselective: A high-yielding two-step indole ring installation comprising the Stille cross-coupling and a PdII-mediated oxidative heterocyclization was exploited in a concise total synthesis of paspalinine. The trans-anti-trans CDE fused ring system of the heptacyclic natural product was established highly stereoselectively through hydroxy-directed cyclopropanation and allylic selenoxide rearrangement.,10.1002/anie.201206299,2012-11-07,0.6108999422347607
Angewandte Chemie International Edition,Irreversible Inhibition of Metallo‐β‐lactamase (IMP‐1) by 3‐(3‐Mercaptopropionylsulfanyl)propionic Acid Pentafluorophenyl Ester,Resistance is futile: Pathogenic bacteria that produce metallo-β-lactamases are recognized as a serious threat because of their resistance to antibiotics. The title compound has now been shown to be an irreversible inhibitor for a metallo-β-lactamase (IMP-1). The X-ray crystallographic structure (see picture) has revealed that the inhibitor binds to IMP-1 with formation of a covalent amide bond with the amino group (Nζ) of Lys 224.,10.1002/anie.200500835,2005-05-13,0.610888851376098
Journal of Organic Chemistry,"A Catalytic Asymmetric Protecting-Group-Free Total Synthesis of (4<i>S</i>,5<i>S</i>)-4,8-Dihydroxy-3,4-dihydrovernoniyne and Its Enantiomer",")-4,8-dihydroxy-3,4-dihydrovernoniyne has been completed employing the asymmetric dihydroxylation strategy. Further, a four-step protecting-group-free synthesis of the natural product and its enantiomer has been achieved through the modified Knoevenagel reaction, asymmetric dihydroxylation, and Cadiot-Chodkiewicz coupling. The protecting-group-free synthesis is completed in four steps and 41% overall yield.",10.1021/acs.joc.9b02461,2019-09-19,0.6108690725190898
Journal of Organic Chemistry,"One-Pot Acid-Promoted Synthesis of 6-Aminopyrazolopyrimidines from 1<i>H</i>-Pyrazol-5-yl-<i>N</i>,<i>N</i>-dimethylformamidines or 5-Amino-1<i>H</i>-pyrazole-4-carbaldehydes with Cyanamide","A convenient and efficient one-pot acid-promoted synthesis of 6-aminopyrazolo[3,4- d ]pyrimidine has been developed by treatment of 1 H -pyrazol-5-yl- N, N -dimethylformamidines or 5-amino-1 H -pyrazole-4-carbaldehydes with cyanamide (NH 2 C≡N) in an acid-mediated solution. This synthetic route involves four steps of deprotection, imination, the key acid-promoted heterocyclization, and aromatization. On the basis of optimized studies, methanesulfonylchloride is considered to be the best solvent. Furthermore, the microwave-assisted synthetic technique was also carried out to improve the major product 6-aminopyrazolo[3,4- d ]pyrimidines in this method. Moreover, our proposed mechanism was confirmed in this study, which demonstrates that N -[(5-amino-1,3-diaryl-1 H -pyrazol-4-yl)methylene]cyanamide is the intermediate.",10.1021/acs.joc.9b02653,2019-11-18,0.6108666282571351
Journal of the American Chemical Society,Asymmetric De Novo Synthesis of a Cucurbitane Triterpenoid: Total Synthesis of Octanorcucurbitacin B,"synthesis of a cucurbitane natural product, octanorcucurbitacin B, has been accomplished. Cucurbitanes are a family of structurally complex triterpenoids that characteristically contain three stereodefined quaternary centers at ring fusion carbons positioned about their tetracyclic skeletons (at positions 9, 13, and 14). Taking a diversion from the biosynthetic hypothesis for cucurbitane synthesis, the approach established here provides direct access to the cucurbitane skeleton without having to proceed by way of a lanostane. Using a simple chiral enyne as starting material, a sequence of annulative cross-coupling and intramolecular Heck reaction provides a stereodefined polyunsaturated tetracycle possessing the C9 and C13 quaternary centers. This intermediate was converted to octanorcucurbitacin B through a 12-step sequence that features hydroxy-directed Simmons-Smith cyclopropanation, regioselective deconjugative alkylation, and allylic oxidation.",10.1021/jacs.2c03109,2022-05-09,0.610865054996195
Synlett,Synthesis of a Novel Rhizobitoxine-Like Triazole-Containing Amino Acid,"The synthesis of the four stereoisomers of a new 1,2,3-triazole analogue of rhizobitoxine from serine is described. The key step is a Huisgen 1,3-dipolar cycloaddition on an ethynylglycine synthon.",10.1055/s-0036-1588300,2016-08-18,0.6108646194475639
Organic Letters,Total Syntheses of Brominated Marine Sponge Alkaloids,"Total syntheses of six brominated marine sponge bis(indole) alkaloids of the hamacanthin, spongotine, and topsentin classes are described. Retrosynthetic analysis shows that their structures all include the 1-(6'-bromoindol-3'-yl)-1,2-diaminoethane unit 13a. This key moiety has been prepared from brominated indolic N-hydroxylamine 5b via synthetic intermediate 8b.",10.1021/ol701626m,2007-08-18,0.6108641350273912
Organic Letters,A One-Pot–Three-Step Route to Triazolotriazepinoindazolones from Oxazolino-2<i>H</i>-indazoles,"A one-pot-three-step method has been developed for the conversion of oxazolino-2H-indazoles into triazolotriazepinoindazolones with three points of diversity. Step one of this process involves a propargyl bromide-initiated ring opening of the oxazolino-2H-indazole (available by the Davis-Beirut reaction) to give an N(1)-(propargyl)-N(2)-(2-bromoethyl)-disubstituted indazolone, which then undergoes -CH(2)Br → -CH(2)N(3) displacement (step two) followed by an uncatalyzed intramolecular azide-alkyne 1,3-dipolar cycloaddition (step three) to form the target heterocycle. Employing 7-bromooxazolino-2H-indazole allows for further diversification through, for example, palladium-catalyzed coupling chemistry, as reported here.",10.1021/ol3015804,2012-07-23,0.6108525367549308
Synthesis,Review of the Total Synthesis of the Aromatic Abietane Diterpenoid Ferruginol,Abstract The biological properties and synthesis of ferruginol as a classical abietane-type diterpenoid with an aromatic C ring are reviewed. A strategy overview from 1954 to 2023 toward the total synthesis of ferruginol may provide some references for the future design and synthesis of new diterpenoids natural products. 1 Introduction 2 Biological Activity of Ferruginol 3 Strategies toward the Total Synthesis of Ferruginol 3.1 Bogert–Cook Synthesis 3.2 Robinson Annulation 3.3 Domino Synthesis 3.4 Intramolecular Friedel–Crafts Alkylation 3.5 Oxidative Free-Radical Cyclization 3.6 Polyene Cyclization 4 Conclusion and Perspectives,10.1055/a-2186-7983,2023-10-05,0.6108344242618293
Synthesis,"A Convenient Synthetic Route to 2,2′-Biimidazole","All articles of this category Convenient two step procedures for the synthesis of 2,2′-biimidazole ( 3 )and its dihydrochloride salt ( 4 ) starting with bis-methylimidate ( 1 ) in an overall yield of 72 and 83%, respectively, are reported. Bis-methylimidate( 1 ) was treated with two equivalents of aminoacetaldehyde dimethyl acetal underacid-catalyzed conditions to provide bis- N -(2,2-dimethoxyethylacetamidine)dihydrochioride ( 2 ) in 84% yield. Fusion of 2 with an equivalent of p toluenesulfonic acid at 200°C gave 3 in 86% yield. Alternatively, 2 was refluxed with 5 molar hydrochloric acid to provide 4 as well as 3 in combined yield of 99%. Evidence is presented for the intermediacy of 2-[4(5)-methoxy-2-imidazolyl]imidazole ( 5 ) in the formation of the title compound. Water-soluble 4 is converted to 3 by treatment with potassium carbonate.",10.1055/s-1986-31607,1986-01-01,0.6108273435910597
Organic Letters,A Formal Enantioselective Total Synthesis of FR901483,"A formal enantioselective total synthesis of the potent immunosuppressant FR901483 (1) has been accomplished. Our approach features the use of chiron 6 as the starting material, the application of the one-pot amide reductive bisalkylation method to construct the chiral aza-quaternary center (dr = 9:1), regio- and diastereoselective intramolecular aldol reaction to build the bridged ring, and ring closing metathesis to form the 3-pyrrolin-2-one ring.",10.1021/ol302165d,2012-08-31,0.6108218260033483
Journal of Organic Chemistry,"De Novo Synthesis of Long-Wavelength Absorbing Chlorin-13,15-dicarboximides","Chlorins bearing a six-membered imide ring spanning positions 13-15, commonly referred to as purpurinimides, exhibit long-wavelength absorption yet have heretofore only been available via semisynthesis from naturally occurring chlorophylls. A concise route to synthetic chlorins, which bear a geminal dimethyl group in the pyrroline ring, has been extended to provide access to chlorin-13,15-dicarboximides. The new route entails (i) synthesis of a 13-bromochlorin, (ii) palladium-catalyzed carbamoylation at the 13-position, (iii) regioselective 15-bromination under acidic conditions, and (iv) one-flask palladium-mediated carbonylation and ring closure to form the imide. In some cases the ring closure reaction afforded the isomeric (and readily separable) chlorin-isoimide in addition to the chlorin-imide. The resulting chlorin-imides and chlorin-isoimides exhibit long-wavelength absorption (679-715 nm) and emission (683-720 nm) in the far-red and near-infrared spectral region. The absorption of the chlorin-(iso)imides fills the spectral window between that of analogous synthetic chlorins and 13(1)-oxophorbines (603-687 nm) and bacteriochlorins (707-792 nm). The synthetic versatility of the de novo route complements the existing semisynthetic route from chlorophylls and should enable fundamental spectroscopic studies and photochemical applications.",10.1021/jo902649d,2010-02-01,0.610811909607513
Tetrahedron,A novel and convenient route to cyclic and acyclic carbonates from unprotected methyl d-glycosides,,10.1016/0040-4039(91)85076-h,1991-06-01,0.6108078789132989
Synlett,Synthesis of Novel Polyhydroxylated Tetrahydropyranopyrroles,The stereoselective access to original polyhydroxylated tetrahydropyranopyrroles is described. The key steps involve an ­inverse-demand Diels-Alder reaction and a ring contraction of a ­pyridazine heterocycle.,10.1055/s-2007-968030,2007-02-01,0.6107897462065752
Synlett,A Short and Efficient Synthesis of a C1-C9 Intermediate Towards Maytansine,"All articles of this category A short synthesis of highly functionalised 3 S ,6 R ,7 S )-4-nonene 1 , C1-C9 intermediate for maytansine, was achieved starting from propyne and ( S , S )-1-( p -toluenesulphonyloxy) -2,3-epoxybutane ( 3 ).",10.1055/s-1992-21334,1992-01-01,0.6107869720638395
Synthesis,"Three Routes for the Synthesis of 6-Benzyl-1-ethoxymethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carbaldehyde","All articles of this category 6-Benzyl-1-ethoxymethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carbaldehyde ( 1 ) is an analog of MKC-442, a very potent inhibitor of HIV-1 reverse transcriptase. Compound 1 was synthesized by three different routes. 6-Benzyl-1-ethoxymethyl-5-vinyl-1 H -pyrimidine-2,4-dione ( 7 ) was synthesized in five steps from 6-benzyl-1 H -pyrimidine-2,4-dione ( 2 ) by iodination; N-1 alkylation, N-3 protection, Pd(0) catalyzed coupling with tetravinyltin and then N-3 deprotection. Compound 7 was then cleaved with ozone to give compound 1 . In another route compound 2 was hydroxymethylated, oxidized and N-1 alkylated to give compound 1 . Finally, compound 1 was synthesized from 6-benzyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile ( 10 ) by reduction with Raney Nickel followed by N-1 alkylation. An attempt was made to use compound 7 as a precursor for 6-benzyl-1-ethoxymethyl-5-oxiranyl-1 H -pyrimidine-2,4-dione ( 11 ) by reacting 7 with MCPBA, but compound 11 was too reactive and was ring-opened by the m -chlorobenzoate present in the solution. Two intermediates were N-1 alkylated to give new MKC-442 analogs containing a hydroxymethyl group ( 13 ) or a cyano group ( 14 ) in the C-5 position. None of the compounds showed activity against the mutated HIV-1 virus (Tyr181Cys) but good activities were observed against wild-type HIV-1 for the intermediates 4 and 7 containing iodine or a vinyl group in the C-5 position, respectively. HIV-1 - non-nucleoside reverse transcriptase inhibitors - MKC-442 analogs - uracil-5-carbaldehydes - 5-vinyluracils",10.1055/s-2001-12352,2001-01-01,0.610784005413523
Organic Letters,Biomimetic Total Synthesis of Bimagnolignan: A Natural Anti-Breast Cancer Agent,"A short scalable biomimetic route to bioactive natural product bimagnolignan ( 1 ) was accomplished. Compound 1 was successfully prepared through a three-step metal-free synthesis from honokiol ( 2 ). Alternatively, 1 was also synthesized by biomimetic transformations that mimic tyrosinase in four steps. The key reactions feature a regioselective acetylation, a highly efficient C(sp 2 )–H oxidation, a cascade aerobic oxidative cyclization/coupling, and a Cu-catalyzed direct oxidative coupling. In addition, cell-based assays validate that 1 is a promising natural lead for HER2-positive breast cancer treatment.",10.1021/acs.orglett.4c00378,2024-03-14,0.6107805725124795
Tetrahedron,Synthesis of the potent antitumoral marine alkaloid variolin B,,10.1016/s0040-4039(01)02321-8,2002-02-01,0.6107705569134905
Tetrahedron,A formal synthesis of ptaquilosin the aglycon of a potent bracken carcinogen ptaquiloside,,10.1016/0040-4039(95)01552-s,1995-10-01,0.6107705569134905
Tetrahedron,"Stereocontrolled synthesis of a potent antimalarial alkaloid, (+)-febrifugine",,10.1016/j.tetlet.2004.06.100,2004-08-01,0.6107705569134905
Organic Letters,Novel Synthesis of 5-Amino-3-bromo-1-(<i>tert-</i>butyl)-1<i>H</i>-pyrazole-4-carbonitrile: A Versatile Intermediate for the Preparation of 5-Amino-3-aryl-1-(<i>tert-</i>butyl)-1<i>H</i>-pyrazole-4-carboxamides,"A simple, novel, and efficient route for the synthesis of 5-amino-3-aryl-1-(tert-butyl)-1H-pyrazole-4-carboxamides 1 has been devised. Preparation of pyrazole bromide 3 from potassium tricyanomethanide can be accomplished in only two steps in good yield and features a selective Sandmeyer reaction on the corresponding diaminopyrazole. This allows for a more versatile synthesis of 5-amino-3-aryl-1-(tert-butyl)-1H-pyrazole-4-carboxamides 1 than was previously possible.",10.1021/ol301655f,2012-07-18,0.6107674554203255
Angewandte Chemie International Edition,A Concise Approach to Vinigrol,Short and sweet: A simple and practical route to the unusual tricyclic ring system found in the biologically active diterpene vinigrol is described. A remarkable proximity-induced intramolecular cycloaddition and mild Grob fragmentation allow rapid construction of the core ring system in less than 10 steps and with a minimal reliance on protecting groups.,10.1002/anie.200800167,2008-03-12,0.6107544236503004
Organic Letters,"Stereoselective Synthesis of 1,3-<i>anti</i> Diols by an Ipc-Mediated Domino Aldol-Coupling/Reduction Sequence","A novel domino process for 1,3-anti diol synthesis by the union of a methyl ketone with an aldehyde is described. The operationally simple procedure is based on an Ipc-boron-aldol coupling and subsequent Ipc-mediated reduction of the intermediate β-hydroxy-ketone. The sequence proceeds with excellent anti-selectivities and enables the rapid construction of complex polyketide fragments.",10.1021/ol3033303,2012-12-21,0.610753860650643
Angewandte Chemie International Edition,Protecting‐Group‐Free Formal Synthesis of Platensimycin,"Short cut: In a new approach to the recently discovered antibiotic platensimycin (1), Nicolaou's late key intermediate is synthesised without the use of protecting groups in five steps from a readily available starting material.",10.1002/anie.200702852,2007-09-14,0.6107530156533955
Tetrahedron,A practical dinucleotide phosphoramidite chemistry for de novo DNA synthesis via block coupling,,10.1016/j.tetlet.2024.155106,2024-05-11,0.6107502343000532
Journal of the American Chemical Society,Asymmetric Total Synthesis of Propindilactone G,"A concise total synthesis of (+)-propindilactone G, a nortriterpenoid isolated from the stems of Schisandra propinqua var. propinqua, has been achieved for the first time. The key steps of the synthesis include an asymmetric Diels-Alder reaction, a Pauson-Khand reaction, a Pd-catalyzed reductive hydrogenolysis reaction, and an oxidative heterocoupling reaction. These reactions enabled the synthesis of (+)-propindilactone G in only 20 steps. As a consequence of our synthetic studies, the structure of (+)-propindilactone G has been revised.",10.1021/jacs.5b06480,2015-07-16,0.6107434516974792
Tetrahedron,"Diastereoselective and highly efficient radical approach to (1S,6R) and (1R,6S)-2,2,6-trimethyl-3-oxabicyclo[4.2.0]octadecane, key intermediates in the synthesis of (+) and (−)-grandisol",,10.1016/s0040-4039(00)77178-4,1994-04-01,0.6107403312795742
Tetrahedron,"Eupachlorin acetate, a novel chloro-sesquiterpenoid lactone tumor inhibitor from",,10.1016/s0040-4039(01)99098-7,1968-01-01,0.610739939394194
Synlett,"A Facile, Inexpensive and Scalable Route to Thiol-Protected α-Methyl Cysteine","A facile, scalable synthesis of α-methyl cysteine with three alternate thiol protecting groups (trityl, allyl and tert -butyl) is described. The thiol-protected amino acids are obtained in six steps from l -cysteine ethyl ester and are ideally suited for a range of natural product and solid-phase peptide synthesis applications.",10.1055/s-0032-1318316,2013-02-25,0.6107273340969114
Synlett,Synthesis of Eleven-Membered Cyclic Urea Fused Quinazolinones,"Abstract Straightforward synthesis of quinazolinones having N-fused medium-sized ring urea was accomplished. Key intermediates were tert-butyl {2-[4-oxo-2-(4-oxopentyl)quinazolin-3(4H)-yl]ethyl}carbamates derived from copper-catalyzed domino reaction of tert-butyl [2-(2-iodobenzamido)ethyl]carbamates and cyclic enaminones. Steric hindrance of cyclic enaminones played an important role in the formation of quinazolinone ring. The eleven-membered ring urea moiety was readily achieved by direct cyclization using 1,1′-carbonyldiimidazole (CDI) of diamino intermediate generated by readily reductive amination and deprotection of tert-butyl {2-[4-oxo-2-(4-oxopentyl)quinazolin-3(4H)-yl]ethyl}carbamates.",10.1055/a-1793-1321,2022-03-09,0.6107260304799178
Journal of the American Chemical Society,Total Synthesis of Clavepictines A and B. Diastereoselective Cyclization of δ-Aminoallenes,"The stereocontrolled total synthesis of (−)-clavepictine A ( 1A ) and (+)-clavepictine B ( 1B ) has been accomplished in an enantioselective fashion, which has unequivocally established the absolute configuration of 1A and 1B . The pivotal step in the synthesis is diastereoselective silver(I)-promoted cyclization of δ-amino allenes. Another key method includes cross-coupling of enol triflates of N -acyl lactams, which allows stereocontrolled functionalization of otherwise unreactive lactams under mild conditions. The utility of Beak's α-lithiation-substitution chemistry of N -BOC piperidines involving a functionalized aldehyde as the electrophile is demonstrated in the preparation of highly substituted nitrogen heterocycles. These new synthetic strategies should be of general synthetic utility in the stereoselective syntheses of quinolizidines, indolizidines, and related aza-heterocylces. Also included is the unique conformational preference of the highly substituted cis -quinolizidine core of clavepictines; the (superfluous) m -(trifluoromethyl)benzoate substituent has a surprisingly significant influence on the relative energies of the two possible chair−chair conformations.",10.1021/ja9925958,1999-10-15,0.6107231528719251
Synthesis,Facile Synthesis of Thymidine Derivatives by Cross-Coupling of 5-Halogenouridine Derivatives with Trimethylaluminum,"All articles of this category An efficient method for the introduction of a methyl group in the 5-position of uridine derivatives is described. This method involves three steps: protection of 5-halogenouridines 4 and 5 with hexamethyldisilazane, a palladium-catalyzed cross-coupling of the pertrimethylsilylated nucleosides with trimethylaluminum, and subsequent deprotection to afford the corresponding thymidine derivatives 6 in high overall yields.",10.1055/s-1993-25833,1993-01-01,0.6107223436438807
Journal of the American Chemical Society,A Concise Approach to Anthraquinone–Xanthone Heterodimers,A synthetic approach to anthraquinone-xanthone heterodimers is described. The route to the pentacyclic core features an efficient assembly of a benzocycloheptenone via a new intramolecular oxidative arylation of an enol ether and a Hauser-Kraus annulation-aldol reaction sequence to access the characteristic bicyclo[3.2.2]nonene motif. Acremoxanthone A is synthesized in 10 steps from commercially available material to demonstrate the application of this approach.,10.1021/jacs.8b03110,2018-04-05,0.6107137709761988
Synthesis,"Expeditious Synthesis of the Topoisomerase I Inhibitors Isoindolo[2,1-b]isoquinolin-7(5H)-one and the Alkaloid Rosettacin Based on Aryl Radical Cyclization of Enamide Generated by Using N-Acyliminium Chemistry","A short and effective approach to the synthesis of the topoisomerase I inhibitor isoindolo[2,1- b ]isoquinolin-7(5 H )-one and the alkaloid rosettacin belonging to the aromathecin family is presented. The key step of this sequence, which resulted in the formation of a five-membered ring, was the aryl radical cyclization of enamides generated using N -acyliminium chemistry.",10.1055/s-0034-1378811,2015-09-07,0.6106923215197557
Synthesis,A Convenient and Expedient Synthesis of 3-Aryl-2<i>H</i>-azirine-2-carboxaldehydes,"A new procedure for the synthesis of 3-aryl-2H-azirine-2-carboxaldehydes starting from cinnamyl alcohols is disclosed. This novel approach implies milder conditions and higher overall yields as compared to the previously reported methods. The key step, i.e. the formation of the azirine ring, involves the treatment of (Z)-3-aryl-3-azidoprop-2-en-1-ols with MnO2.",10.1055/s-2003-36255,2003-01-01,0.6106916961816795
Journal of Organic Chemistry,Enantioselective Total Synthesis and Stereochemical Revision of Communiols E and F,"The enantioselective total synthesis of candidate structures for communiols E and F, novel bicyclic polyketides of fungal origin, was accomplished using a Lewis acid-mediated ring closure reaction of an allylsilane intermediate as the key step. Comparison of the spectral data of the synthetic materials with those of natural communiols E and F, coupled with biosynthetic considerations, led to the conclusion that the stereochemistry of communiols E and F should be (2S,5S,7R, 8S,11R)- and (5S,7R,8S,11R)-forms, respectively.",10.1021/jo0608927,2006-07-07,0.6106864334393598
Tetrahedron,Synthesis of a dextrophane prototype: a novel cavity molecule,,10.1016/s0040-4039(00)61827-0,1987-01-01,0.6106847960880789
Synthesis,Studies Directed Towards the Total Synthesis of (+)-Himbacine,"A convergent strategy towards himbacine (1), involving a Julia coupling between aldehyde 5 and sulfone 6 was found to be ineffective. The aldehyde 5 was synthesized via the thermal intramolecular cycloaddition of 4 with preferred formation of the endo-adduct. The Diels-Alder precursor 4 was obtained from butenolide 7, the result of a single-step condensation between the enoate derived from the (Z)-conjugated olefin 12 and 2-acetoxypropanal. In the context of the synthesis of sulfone 6 Taber's method for the synthesis of 2,6-trans-disubstituted piperidine was adapted towards a large scale synthesis of 49, a useful intermediate for the synthesis in this area.",10.1055/s-1998-5928,1998-03-01,0.6106832649870211
Journal of Organic Chemistry,Total Synthesis of (+)-Sieboldine A: Evolution of a Pinacol-Terminated Cyclization Strategy,"This article describes synthetic studies that culminated in the first total synthesis of the Lycopodium alkaloid sieboldine A. During this study, a number of pinacol-terminated cationic cyclizations were examined to form the cis-hydrindanone core of sieboldine A. Of these, a mild Au(I)-promoted 1,6-enyne cyclization that was terminated by a semipinacol rearrangement proved to be most efficient. Fashioning the unprecedented N-hydroxyazacyclononane ring embedded within the bicyclo[5.2.1]decane-N,O-acetal moiety of sieboldine A was a formidable challenge. Ultimately, the enantioselective total synthesis of (+)-sieboldine A was completed by forming this ring in good yield by cyclization of a protected-hydroxylamine thioglycoside precursor.",10.1021/jo300872y,2012-06-26,0.6106796607106756
Synlett,A New Total Synthesis of (+)-Brefeldin C,"A new synthesis of (+)-brefeldin C featuring a Bolm desymmetrisation reaction, a B-alkyl Suzuki-Miyaura cross-coupling and a Carreira alkynylation reaction as the key steps is reported.",10.1055/s-2004-835669,2004-11-12,0.6106787858759779
Angewandte Chemie International Edition,Asymmetric Total Synthesis of Alstrostine G Utilizing a Catalytic Asymmetric Desymmetrization Strategy,"A highly effective enantioselective monobenzoylation of 1,3-diols has been developed for the synthesis of 1,1-disubstituted tetrahydro-β-carbolines. The chemistry has been successfully applied to the asymmetric total synthesis of (+)-alstrostine G, which also features a cascade Heck/hemiamination reaction enabling facile construction of the pivotal pentacyclic core.",10.1002/anie.202407127,2024-05-31,0.6106780988376581
Tetrahedron,An expedient route to a versatile intermediate for the stereoselective synthesis of all-trans-retinoic Acid and beta-carotene,,10.1016/0040-4039(93)88020-j,1992-12-01,0.610660231798863
Synthesis,"Stereoselective Reduction of β-Hydroxy α-Ketoesters: A Concise Synthesis of<i>anti</i>-α,β-Dihydroxy Esters","A new synthetic route to anti-α,β-dihydroxy esters has been developed. The new method consists of three steps starting from an aldehyde: the nucleophilic condensation with ethyl diazo­acetate, oxidation with dimethyldioxirane, and stereoselective reduction with NaBH4.",10.1055/s-2004-831210,2004-01-01,0.6106580330119553
Organic Process Research & Development,New Synthetic Approach to 4-(3-Aminopropyl)-5-amino-1-methylpyrazole Starting from 3-Cyanopyridine,"A short and practical method for the synthesis of 4-( N -Boc-3-aminopropyl)-5-( N -tritylamino)-1-methylpyrazole ( 3 ), side chain of an anti- Pseudomonas aeruginosa cephalosporine FR259647, 1, was established by utilizing a regioselective enamine exchange with N -methylhydrazine and 1,4,5,6-tetrahydro-pyridine-3-carbonitrile ( 8 ), followed by a subsequently occurring intramolecular cyclization and aromatization, starting from a cheap 3-cyanopyridine ( 7 ).",10.1021/op0501996,2005-12-14,0.6106544709366343
Organic Letters,Concise Total Syntheses of the <i>Lycopodium</i> Alkaloids (±)-Nankakurines A and B via Luciduline,"Total syntheses of the Lycopodium alkaloids nankakurines A and B have been accomplished in 6 and 7 steps, respectively, via a sequence that passes through a third Lycopodium alkaloid, luciduline, and forgoes the use of protecting groups on nitrogen. Key features include a short preparation of luciduline followed by a concise and stereoselective aminoallylation/ring-closing metathesis protocol to fashion the spiropiperidine ring common to nankakurines A and B.",10.1021/ol902455y,2009-12-16,0.6106521033512566
Tetrahedron,Asymmetric and diastereodivergent approach to key intermediates for the synthesis of homopumiliotoxin 223G and epiquinamide isomer,,10.1016/j.tetlet.2009.10.098,2009-10-30,0.6106431214995536
Synlett,A Short and Highly Diastereoselective Synthesis of Verbalactone,Verbalactone has been synthesized in seven steps in good yield from commercially available hexanal using highly dia­stereo- and enantioselective allylmetalations and a Yamaguchi ­macrolactonization.,10.1055/s-2007-967946,2007-02-01,0.6106365222865239
Organic Letters,Studies toward the Total Syntheses of Calyciphylline D-Type <i>Daphniphyllum</i> Alkaloids,"An efficient construction of an aza-[5.7.6.5] tetracyclic core structure of calyciphylline D-type Daphniphyllum alkaloids has been achieved. The synthetic route features a diastereoselective cyclopropanation, efficient construction of the core bridged 8-aza-[3.2.1]octane skeleton through a [3 + 2] IMCC strategy, oxidative dearomatization of phenol, and gram-scale preparation in each step.",10.1021/acs.orglett.1c03497,2021-11-18,0.6106301880185023
Tetrahedron,Reductive desilanolation as a route to benzonitriles. An application to a concise synthesis of the aromatic sector of calicheamicin,,10.1016/s0040-4039(00)78380-8,1994-10-10,0.6106224142236479
Tetrahedron,Reductive desilanolation as a route to benzonitriles. An application to a concise synthesis of the aromatic sector of calicheamicin,,10.1016/0040-4039(94)80006-5,1994-10-01,0.6106224142236479
Synthesis,A Simple Stereoselective Synthesis of a Novel Cytotoxic Alkaloid Barrenazine A¹,The cytotoxic marine alkaloid barrenazine A was synthesized stereoselectively in eight simple steps from octanal. A key step involved the preparation of a functionalized 4- aminopiperidin-5-ol that underwent oxidative dimerization on treatment with 2-iodoxybenzoic acid.,10.1055/s-0030-1260081,2011-06-21,0.610621627601943
Organic Letters,Asymmetric Total Synthesis of (−)-Juvabione via Sequential Ir-Catalyzed Hydrogenations,"(-)-Juvabione, a natural sesquiterpene exhibiting juvenile insect hormone activity, was synthesized constructing the two adjacent stereogenic centers via sequential Ir-catalyzed hydrogenations. The first center is generated by hydrogenation of a styrene-type double bond (99% ee). The successive monohydrogenation of a diene intermediate constitutes the key step, granting high levels of regio- and stereocontrol (94:6 dr). This novel strategy allowed the preparation of (-)-juvabione from simple starting materials in 9 steps and 17% total yield.",10.1021/acs.orglett.8b02405,2018-08-31,0.6106168558181654
Angewandte Chemie International Edition,A One‐Pot Total Synthesis of Crambin,"Making up for lost time: The one-pot synthesis of crambin (see structure) with only a single final purification step gave the target protein of exceptional purity in only two days with an overall yield of ≈40 %. Three unprotected peptide segments were linked by native chemical ligation, and the polypeptide chain assumed its 3D structure without intermediate purification steps.",10.1002/anie.200353540,2004-04-28,0.6106116035674664
Journal of Organic Chemistry,"Total Synthesis of Neuroprotectin D1 Analogues Derived from Omega-6 Docosapentaenoic Acid (DPA) and Adrenic Acid (AdA) from a Common Pivotal, Late-Stage Intermediate","The first total synthesis of three omega-6 dihydroxylated (E,E,Z)-docosatrienes has been successfully achieved employing a flexible strategy. The key features encompass a Boland semireduction, to create the (E,E,Z)-triene via an (E,E)-ynediene, and a selective deprotection of a tris(tert-butyldimethylsilyl) ether. The main advantage of the present strategy over previous syntheses of noncyclic dihydroxylated PUFA metabolites derived from docosahexaenoic and arachidonic acids comes from the introduction of the polar head chain at the very end of the synthesis from an advanced, pivotal aldehyde. In terms of divergency this enables late-stage modification of the head group.",10.1021/jo500147r,2014-02-26,0.6105990703996085
Journal of the American Chemical Society,Total Synthesis of Tagetitoxin,"The intriguing structure of tagetitoxin ( 1 ), a long-standing challenge in natural product synthesis, has been the subject of multiple revisions and has been confirmed through total synthesis. The route commences from a renewable furan starting material and features a number of unusual transformations (such as rearrangements, bromocyclization, and P(V)-based phosphate installation) to arrive at the target in 15 steps. As the route was designed to enable access to both enantiomers, the absolute configuration of the natural product could be assigned using a bioassay on (+)- 1 and (−)- 1 .",10.1021/jacs.0c06641,2020-07-20,0.6105972125411236
Journal of Organic Chemistry,Concise Total Synthesis of (+)-Lanceolactone A: Revision of Absolute Stereochemistry,"A chiral-pool protecting-group-free five-step total synthesis of tetranorsesquiterpenoide (+)-lanceolactone A and all of its four stereoisomers using ( S )-(+)-, and ( R )-(−)-linalool (coriandrol) as building blocks is disclosed. The key steps involved in this synthetic route are regioselective ozonolysis, Au(I)-catalyzed cycloisomerization-induced construction of furan from alleneone, and dye-sensitized photo-oxidation (through 1 O 2; singlet oxygen) of hydroxyalkyl-tethered furan to access oxaspirolactone. After a thorough evaluation of electronic circular dichroism (ECD) and optical rotation data of all possible stereoisomers, the absolute configuration of natural lanceolactone A at the C4 and C7 positions has been assigned as (+)-(4 S,7 S ), which is an enantiomer to the initially proposed structure (+)-(4 R,7 R ). Further, these investigations led us to extend Feringa and Gawronski’s CD correlation method to [5,5]- and [6,5]-oxaspirolactones.",10.1021/acs.joc.2c01450,2022-09-28,0.6105942663708576
Organic Process Research & Development,Multi-Kilo Delivery of AMG 925 Featuring a Buchwald–Hartwig Amination and Processing with Insoluble Synthetic Intermediates,"The development of a synthetic route to manufacture the drug candidate AMG 925 on kilogram scale is reported herein. The hydrochloride salt of AMG 925 was prepared in 23% overall yield over eight steps from commercially available raw materials, and more than 8 kg of the target molecule were delivered. The synthetic route features a Buchwald–Hartwig amination using BrettPhos as ligand and conducted to afford 12 kg of product in a single batch. In addition, this work highlights the challenges associated with the use of poorly soluble process intermediates in the manufacture of active pharmaceutical ingredients. Creative solutions had to be devised to conduct seemingly routine activities such as salt removal, pH adjustment, and heavy metal scavenging due to the low solubility of the process intermediates. Finally, a slurry-to-slurry amidation protocol was optimized to allow for successful scale-up.",10.1021/op500367p,2015-02-23,0.610588912827777
Organic Letters,Efficient Large Scale Syntheses of 3-Deoxy-<scp>d</scp>-manno-2-octulosonic acid (Kdo) and Its Derivatives,"An efficient method to rapidly synthesize 3-deoxy-D-manno-2-octulosonic acid (Kdo) and its derivatives in large scale has been developed. Starting from D-mannose, the di-O-isopropylidene derivative of Kdo ethyl ester was prepared in three steps on a scale of more than 40 g in one batch in an overall yield of 75-80% without any intermediate purification. Kdo, Kdo glycal, and 2-acetylated Kdo ester were synthesized quickly in high yield from a di-O-isopropylidene derivative of Kdo ethyl ester. 2-Deoxy-β-Kdo ester was obtained with high stereoselectivity via the epimerization of the α-isomer using t-BuOH as a proton source.",10.1021/acs.orglett.5b00901,2015-04-30,0.6105778904413447
Organic Letters,Total Syntheses of (−)-Hibiscone C and Lysergine: A Cyclization/Fragmentation Strategy,The first asymmetric total synthesis of (-)-hibiscone C and a concise synthesis of ergot alkaloid lysergine are described. Both syntheses were achieved using the radical cyclization/fragmentation strategy. This cascade reaction enabled the application of the strained bicycle as a synthon for the synthesis of highly substituted decalins in an efficient and stereoselective manner.,10.1021/acs.orglett.6b03778,2017-01-20,0.6105743789854312
Synlett,"Enantioselective Synthesis of a (1R,5R,9R)-2-Azabicyclo[3.3.1]nonane-9-carboxylic Acid with an Embedded Morphan Motif: A Multipurpose Product","A convenient asymmetric synthesis of (1 R ,5 R ,9 R )-2-aza­bicyclo[3.3.1]nonane-9-carboxylic acid is described, starting from (2 E ,7 E )-dimethyl nonadienedioate. The route involves a stereo­selective domino Michael–Dieckman process that furnishes a 1,2,3-trisubstituted cyclohexane derivative bearing three adjacent stereocenters with full stereochemical control. A subsequent chemoselective transformation of one of the side-chain ester groups allows an effective second cyclization leading to the morphan motif. The versatility of this novel amino acid for the generation of molecular complexity was tested by elaborating a tripeptide in homogeneous phase.",10.1055/s-0032-1317950,2013-01-04,0.6105687177056661
European Journal of Organic Chemistry,Asymmetric Synthesis of 3-Oxacarbacyclin and 3-Oxaisocarbacyclin by a Common Enantioselective Deprotonation Based Route,"Asymmetric total syntheses of 3-oxacarbacyclin (4) and 3-oxaisocarbacyclin (5) have been achieved by a new and common route. The key step of these syntheses is an enantioselective deprotonation of the prochiral ketone 25 with lithium (R,R)-bis(phenylethyl)amide (12) in the presence of LiCl. Treatment of the thus formed enolate 26 with ClSiEt3 gave the enol ether 27 of 92% ee in 94% yield. Deprotonation of the analogous prochiral ketone 9 with 12 in the presence of LiCl followed by reaction of the enolate 13 with ClSiEt3 led to isolation of the silyl enol ether 8b of 92% ee in 95% yield. A study of the deprotonation of 9 with the chiral lithium amides 14−19 showed that 12 in combination with LiCl is the optimal base in terms of enantioselectivity and accessibility. The ω-side chain in 4 and 5 was established by a Mukaiyama reaction of 27 with the unsaturated aldehyde 28, leading to ketone 39 of 90% de, in combination with a stereoselective Pd-catalyzed allylic rearrangement of acetate 47 to the isomeric acetate 48 and a Mitsunobu reaction of the allylic alcohol 49. The key step in the construction of the α-side chain in 4 is a Horner-Wadsworth-Emmons reaction of ketone 7c with the 8-phenylnormenthol-containing phosphonoacetate 56 which gave ester 60 of 90% de. Ester 60 was obtained diastereomerically pure by chromatography in 72% yield from 7c. Reduction of 60 furnished the allylic alcohol 62 which was converted to 4 in a standard fashion. It is at the stage of the α,β-unsaturated ester 60 where divergence into synthesis of 5 was made. Selective isomerization of 60 to the β,γ-unsaturated ester 66 of 97% ie in 91% yield was accomplished by deprotonation of 60 with 12 to enolate 65 and its subsequent regioselective protonation. By a similar reaction sequence the isomeric α,β-unsaturated ester 61 was converted to the ß,γ-unsaturated ester 69 of 97% ie in 88% yield. Reduction of 66 afforded the homoallylic alcohol 71 which was converted to 5 in a standard fashion.",10.1002/(sici)1099-0690(199805)1998:5<805::aid-ejoc805>3.0.co;2-r,1998-05-01,0.6105675772900322
Organic Letters,Total Synthesis of (−)-Owerreine and (−)-Anhydrovobtusine,"We report the first total synthesis of the heterodimeric aspidosperma-aspidosperma alkaloids (-)-owerreine and (-)-anhydrovobtusine. Our synthesis of these bisindole alkaloids was achieved via a late-stage double C7 methylenation sequence, leading to the union of two hexacyclic aspidosperma components. Our synthetic strategy was based on our hypothesis for the biosynthesis of these alkaloids and required the directed assembly of complex fragments related to natural alkaloids (-)-beninine (the northern half) and (-)-deoxoapodine (the southern half). The (-)-beninine-related intermediate was accessed via an oxidative Pd-catalyzed intramolecular C6'-O bond formation, an Ir-catalyzed C17' boronation as a prelude to introduction of the C17'-ether, and transannular spiro-cyclization to afford the C12'-C19' bond. A readily available and enantiomerically enriched lactam, previously used in our total synthesis of (-)-deoxoapodine, served as the common precursor to both halves of these bisindole alkaloids.",10.1021/acs.orglett.5c04148,2025-11-05,0.6105497829212312
Tetrahedron,"A general synthetic route to 3,9-dialkyladenines and their ring opening",,10.1016/s0040-4039(01)85794-4,1978-01-01,0.61054814320211
Journal of Organic Chemistry,"Highly Stereocontrolled Synthesis of <i>trans</i>-2,6-Disubstituted-5-methyl-3,6-dihydropyrans: Stereoselective Synthesis of the Bicyclic Core of Penostatin B","An efficient, mild, and highly diastereoselective strategy for the synthesis of trans-2,6-disubstituted-5-methyl-3,6-dihydropyran ring systems has been developed starting from δ-hydroxy α-methyl α,β-unsaturated aldehydes and allyltrimethylsilane in the presence of a catalytic amount of ZnBr2 in a highly diastereoselective manner with excellent yield. The versatility of the above method was also demonstrated for the construction of the bicyclic core present in penostatin B in a concise and highly stereoselective manner.",10.1021/jo502101u,2015-01-13,0.6105436528751791
Journal of Organic Chemistry,Domino Knoevenagel Condensation/Intramolecular Aldol Cyclization Route to Diverse Indolizines with Densely Functionalized Pyridine Units,"A highly efficient [4 + 2] annulation route to polysubstituted indolizines is described employing a domino Knoevenagel condensation/intramolecular aldol cyclization process as a key step. Construction of pyridine rings in indolizine skeleton was rapidly achieved from several pyrrole-2-carboxaldehydes in good to excellent yields, leading to indolizines with various substituents at the 5, 6, and 7 positions depending on the reacting active methylene partners.",10.1021/jo401801j,2013-09-25,0.6105358648423015
Organic Letters,"First Asymmetric Synthesis of <i>trans</i>-3,4-Dimethyl-4-arylpiperidines","The first asymmetric synthesis of the trans-3,4-dimethyl-4-arylpiperidine opioid antagonist scaffold is reported. C-3 stereochemistry was established via CBS reduction and stereoselective anti-SN2' cuprate displacement of the derived allylic phosphonate. The resultant vinyl bromide was then elaborated to the target compound by Suzuki coupling and trans-selective 4-methylation. Extension of this methodology should allow general enantioselective access to highly substituted piperidine ring systems.",10.1021/ol0713988,2007-08-21,0.6105198623681845
Tetrahedron,A new route to steroidal vinyl fluorides,,10.1016/0040-4039(94)88168-5,1994-01-01,0.6105127884465293
Tetrahedron,A new route to vinyl fluorides,,10.1016/s0040-4039(00)97869-9,1990-01-01,0.6105127884465293
Tetrahedron,"Asymmetric synthesis of cyclopentylamine derivatives, intermediates for carbocyclic nucleoside synthesis. Carbocyclization of 2-amino-5-hexenyl radicals",,10.1016/s0040-4039(00)73433-2,1994-08-01,0.6104990192295043
European Journal of Organic Chemistry,Syntheses of Cyclobutane Derivatives: Total Synthesis of (+) and (–) Enantiomers of the Oleander ScaleAspidiotus nerii Sex Pheromone,"Synthesis of both enantiomers of the Aspidiotus nerii sex pheromone and their diastereomers has been achieved using, as a key step, an intramolecular ester enolate alkylation reaction for the formation of the cyclobutane ring with a good control of the relative configurations of the asymmetric centers. Stereoselective synthesis of a number of other trisubstituted cyclobutane derivatives also proves the versatility of the methodology used for the synthesis of the Aspidiotus nerii sex pheromone.",10.1002/(sici)1099-0690(199905)1999:5<1201::aid-ejoc1201>3.0.co;2-7,1999-05-01,0.6104899247442823
Tetrahedron,A stereoselective synthesis of a key 1β-methylcarbapenem intermediate via a diastereoselective decarboxylation,,10.1016/0040-4039(94)85197-2,1994-04-01,0.6104895076144938
Tetrahedron,"Nucleophilic SN2 displacements on penicillin-6- and cephalosporin-7- triflates; 6β-iodopenicillanic acid, a new β-lactamase inhibitor",,10.1016/0040-4039(80)88017-8,1980-01-01,0.610487963664769
Synlett,"Formal Total Synthesis of (–)-5,6-Dihydrocineromycine B","An efficient and highly convergent formal total synthesis of the 14-membered macrolide (–)-5,6-dihydrocineromycine B is achieved. Key reaction sequences include a Sharpless asymmetric epoxidation followed by esterification for the formation of a fully functionalized acyclic precursor, Corey–Bakshi–Shibata reduction, and ring-closing metathesis, respectively.",10.1055/s-0032-1317346,2012-10-18,0.6104861094703213
Angewandte Chemie International Edition,23‐Oxa‐Analogues of OSW‐1: Efficient Synthesis and Extremely Potent Antitumor Activity,An aldol condensation is the key to the eight-step linear synthesis of 23-oxa analogues of OSW-1 (e.g. 2) in more than 20 % overall yield from the industrially produced steroid 1. Compound 2 is up to 2000 times more potent than cisplatin as an inhibitor of tumor cell growth.,10.1002/anie.200454237,2004-08-13,0.6104857486482118
Organic Letters,Cobalt-Promoted Electroreductive Cross-Coupling of Prop-2-yn-1-yl Acetates with Chloro(vinyl)silanes,"An electroreductive cross-coupling of prop-2-yn-1-yl acetates with chloro(vinyl)silanes for producing tetrasubstituted silylallenes is developed. The method enables the formation of a new C─Si bond through the cathodic reduction formation of the silyl radical, radical addition across the C≡C bond, the alkenyl anion intermediate formation, and deacetoxylation and represents a mild, practical route to the synthesis of silylallenes. Mechanistic studies reveal that CoCl 2 acts as the mediator to promote the formation of the alkenyl anion intermediate via electron transfer.",10.1021/acs.orglett.3c02989,2023-09-27,0.6104560963811846
Organic Process Research & Development,"Process Research and Large-Scale Synthesis of 4‘‘,6‘‘-Bis((2-fluorophenyl)carbamoyl)hecogenyl β-<i>O</i>-Cellobioside:  A Potent Cholesterol Absorption Inhibitor","This paper describes process research leading to the successful scale-up of a potent cholesterol absorption inhibitor 4‘‘,6‘‘-bis((2-fluorophenyl)carbamoyl)hecogenyl β- O -cellobioside 3 . The synthesis of 3 from hecogenyl β- O -cellobioside 4 required five synthetic steps: (1) the selective protection of the 4‘‘,6‘‘-diol group, (2) acylation of the remaining five hydroxyl groups, (3) unmasking of the diol moiety, (4) carbamoylation with 2-fluorophenyl isocyanate, and finally, (5) deacylation. The synthesis by our discovery group utilized chloroacetate protecting groups for five of the sugar alcohols at step two, which led to problems on scale-up due to the instability of this group in solution and the poor crystallinity of the intermediates. Methoxyacetates were identified as the optimal acyl-protecting group. The identification of mild reaction conditions led to an efficient synthesis of bis(carbamate) 3 in very high purity and 42% yield from 4 over five synthetic steps and one recrystallization/polymorph conversion. The process was simple to operate and was carried out to provide 80 kg of 4‘‘,6‘‘-bis(2-fluorophenylcarbamoyl)hecogenyl β- O -cellobioside 3 .",10.1021/op9702206,1998-02-27,0.6104487795403089
Tetrahedron,"Synthetic studies on spider neurotoxins (I): total synthesis of nephilatoxins (NPTX-9) and NPTX-11), new neurotoxins of Joro spider (Nephila clavata)",,10.1016/s0040-4039(00)78872-1,1992-05-01,0.6104477123048984
Journal of Organic Chemistry,"Regioselective Reductive Cleavage of Bis-benzylidene Acetal: Stereoselective Synthesis of Anticancer Agent OGT2378 and Glycosidase Inhibitor 1,4-Dideoxy-1,4-imino-<scp>l</scp>-xylitol","A highly regioselective reductive cleavage of the bis-benzylidene acetal of D-mannitol was performed using a BF(3) x Et(2)O/Et(3)SiH reagent system. A chiral intermediate 6 thus obtained was efficiently utilized in the stereoselective synthesis of the anticancer agent OGT2378 (3) and glycosidase inhibitor derivative N-tosyl 1,4-dideoxy-1,4-imino-L-xylitol (22). Chemoselective reduction of azido epoxide 10 followed by regioselective intramolecular cyclization of amino epoxide 11 resulted in the exclusive formation of deoxyidonojirimycin derivative 12. By changing the order of deprotection, the chiral intermediate 6 was readily transformed to glycosidase inhibitor derivative 22.",10.1021/jo900030p,2009-03-11,0.6104443722437288
Tetrahedron,"Synthesis of GA73 methyl ester, a potent gibberellin-derived antheridiogen from gametophytes of the fern lygodium japonicum",,10.1016/s0040-4039(00)97033-3,1990-01-01,0.6104183459204064
Journal of the American Chemical Society,Exploiting Hidden Symmetry in Natural Products: Total Syntheses of Amphidinolides C and F,"The total synthesis of amphidinolide C and a second-generation synthesis of amphidinolide F have been accomplished through the use of a common intermediate to access both the C1-C8 and the C18-C25 sections. The development of a Ag-catalyzed cyclization of a propargyl benzoate diol is described to access both trans-tetrahydrofuran rings. The evolution of a Felkin-controlled, 2-lithio-1,3-dienyl addition strategy to incorporate C9-C11 diene as well as C8 stereocenter is detailed. Key controlling aspects in the sulfone alkylation/oxidative desulfurization to join the major subunits, including the exploration of the optimum masking group for the C18 carbonyl motif, are discussed. A Trost asymmetric alkynylation and a stereoselective cuprate addition to an alkynoate have been developed for the rapid construction of the C26-C34 subunit. A Tamura/Vedejs olefination to introduce the C26 side arm of amphidnolides C and F is employed. The late-stage incorporation of the C15, C18 diketone motif proved critical to the successful competition of the total syntheses.",10.1021/ja404796n,2013-07-11,0.610405327583664
Tetrahedron,"Asymmetric synthesis of 1,1′-bis(1-hydroxyalkyl)metallocenes and their derivatization to the novel chiral metallocenes with c2 symmetry",,10.1016/0040-4039(95)01968-n,1995-12-01,0.6104051446462131
European Journal of Organic Chemistry,Improved Access to Huprine Derivatives Functionalized at Position 9,"Abstract Herein, we present an improved synthetic pathway to huprine derivatives (the most potent family of non‐covalent acetylcholinesterase inhibitors described to date) with different functional groups at the C9‐position of the scaffold. Our approach enables selection of the desired terminal function prior to construction of the huprine scaffold and consists of three main steps: enol formation from a bicyclic ketone, Suzuki–Miyaura cross coupling with different borane derivatives and a Friedländer condensation to access to the quinoline moiety. This synthetic route was found particularly useful for construction of huprine scaffolds equipped with methylene chains bearing different terminal groups such as hydroxy, azide, nitro, amino and carboxylic groups. These functionalized huprines are used as key intermediates in the preparation of multi‐target directed ligands for the treatment of Alzheimer's disease or in the preparation of resins for purification of cholinesterases by affinity chromatography.",10.1002/ejoc.201501433,2016-02-04,0.6103894845612764
Angewandte Chemie International Edition,Lessons in Strain and Stability: Enantioselective Synthesis of (+)‐[5]‐Ladderanoic Acid,"The synthesis of structurally complex and highly strained natural products provides unique challenges and unexpected opportunities for the development of new reactions and strategies. Herein, the synthesis of (+)-[5]-ladderanoic acid is reported. En route to the target, unusual and unexpected strain release driven transformations were uncovered. This occurrence required a drastic revision of the synthetic design that ultimately led to the development of a novel stepwise cyclobutane assembly by an allylboration/Zweifel olefination sequence.",10.1002/anie.201910901,2019-10-25,0.6103827809394362
Journal of Organic Chemistry,"Total Synthesis of (+)-7,7′-Bistaxodione via Late-Stage Electrochemical Dimerization","The first asymmetric total synthesis of the tetraterpenoid (+)-7,7′-bistaxodione ( 4a ) via a unique late-stage electrochemical oxidative dimerization of a diterpenoid quinone methide tumor Inhibitor (+)-taxodione ( 3a ) has been described. The naturally occurring monomer 3a was synthesized from aromatic abietane diterpenoid, ferruginol (1e) . Further, an efficient convergent synthetic route toward the naturally occurring aromatic abietane terpenoids has been shown via a Lewis acid-mediated diastereoselective cationic epoxy-ene cyclization. This synthetic method directly allows for the formation of a functionalized aromatic abietane scaffold with four contiguous stereogenic centers (two of which are all-carbon quaternary centers).",10.1021/acs.joc.4c02907,2025-01-28,0.6103702231923872
Synthesis,"Chemistry of 3-Hydroxypyridine Part 2: Synthesis of 5,6-Dihalo-3-hydroxypyridines","All articles of this category The multistep synthesis of hitherto unknown 5,6-dihalo-3-hydroxypyridines starting from commercially available 2-hydroxy-5-nitropyridine is described. The suitability of cheap 2-aminomethylfuran (furfurylamine) for the preparation of the title compounds in a novel two step process was also explored.",10.1055/s-1990-26919,1990-01-01,0.6103678075888136
Tetrahedron,Convergent total synthesis of (−)-dactylolide,,10.1016/j.tetlet.2018.01.034,2018-01-13,0.6103660733018317
Tetrahedron,Convergent total synthesis of the michellamines,,10.1016/s0040-4039(00)78358-4,1994-10-01,0.6103660733018317
Tetrahedron,A convergent total synthesis of antiplasmodial C2 symmetric (+)-ekeberin D4,,10.1016/j.tetlet.2013.08.025,2013-08-13,0.6103660733018317
Tetrahedron,"A convergent total synthesis of (+)-anamarine from (R,R)-tartrate and D-gulonolactone",,10.1016/s0040-4039(00)96881-3,1987-01-01,0.6103660733018317
Synthesis,Short Synthesis of (<i>R</i>)- and (<i>S</i>)-4-Amino-3-Hydroxybutyric Acid (GABOB),"A simple and stereospecific synthesis of both (R)- and (S)-GABOB has been developed. The synthetic approach involves the conversion, through organoselenium intermediates, of commercially available ethyl (R)- and (S)-4-chloro-3-hydroxybutyrate into a protected 1,2-amino alcohol with retention of the original configuration.",10.1055/s-2005-861783,2005-01-18,0.6103527402206368
Journal of the American Chemical Society,Asymmetric Total Synthesis of (−)-Plicatic Acid via a Highly Enantioselective and Diastereoselective Nucleophilic Epoxidation of Acyclic Trisubstitued Olefins,"The first total synthesis of (-)-plicatic acid has been achieved by a concise and enantioselective route. In this synthesis, a conceptually new strategy featuring an asymmetric epoxidation-intramolecular epoxy-ring-opening Friedel-Crafts reaction sequence was developed for the stereoselective construction of the 2,7'-cyclolignane skeleton bearing contiguous quaternary-quaternary-tertiary stereocenters. The implementation of this strategy was enabled by the development of a modified protocol for the Seebach epoxidation with TADOOH, which affords an unprecedented, highly enantioselective and diastereoselective epoxidation with a range of alpha-carbonyl-beta-substituted acrylates 3.",10.1021/ja9039407,2009-07-14,0.6103354268992992
Tetrahedron,"Total synthesis of the aglycone of the 8-methyl benzonaphthopyrone antibiotics, gilvocarcin M, virenomycin M, and albacarcin M",,10.1016/s0040-4039(00)86100-6,1988-01-01,0.6103307762463729
Tetrahedron,Lythracea alkaloids. Total synthesis of (±) methyl decinine,,10.1016/s0040-4039(01)82417-5,1974-01-01,0.6103307762463729
Tetrahedron,A stereocontrolled total synthesis of methyl (±)-O-methylpodocarpate,,10.1016/s0040-4039(03)01124-9,2003-06-01,0.6103307762463729
Tetrahedron,A stereocontrolled total synthesis of methyl (±)-O-methylpisiferate,,10.1016/s0040-4039(98)01152-6,1998-08-01,0.6103307762463729
Journal of Organic Chemistry,General Synthesis of Persistent Trityl Radicals for EPR Imaging of Biological Systems,"In this paper we describe the syntheses of the tetraoxygenated triarylmethyl (trityl) radical 14 and the tetrathiatriarylmethyl (trityl) radicals 15 and 16. The syntheses include new and improved preparations of the key intermediate compounds 1 and 2. The new route to compound 2 is noteworthy for its efficiency and its avoidance of the highly toxic compound phosgene as well as the isolation of the air-sensitive 1,2,4,5-benzenetetrathiol.",10.1021/jo011068f,2002-06-18,0.6103253972614127
Journal of Organic Chemistry,"Synthesis of 4(5)-[5-(Aminomethyl)tetrahydrofuran-2-yl- or 5-(Aminomethyl)-2,5-dihydrofuran-2-yl]imidazoles by Efficient Use of a PhSe Group:  Application to Novel Histamine H<sub>3</sub>-Ligands<sup>1</sup>","(+)-4(5)-[(2 R,5 S )-(5-Aminomethyl)tetrahydrofuran-2-yl]imidazole 1 and its C2‘ epimer (−)- 2, which are the 5‘-amino derivatives of a novel imidazole C-nucleoside, were synthesized via β - and α -2‘-phenylselenenyl nucleosides 15 and 16 . The anomers 15 and 16 were provided by a new synthetic method for C-nucleosides via the elimination of PhSeCl and selenocyclization from diol intermediates 12 and 14, starting from l -glutamic acid. Their ent - 1 and ent - 2 (imifuramine), the latter of which was indicated as a novel type of histamine H 3 -agonist confirmed by an in vivo brain microdialysis method, were synthesized by the same methodology from d -glutamic acid. The four isomers ( 3, 4, ent - 3, and ent - 4 ) of a 4(5)-[(5-aminomethyl)-2,5-dihydrofuran-2-yl]imidazole were also synthesized via the oxidative elimination of the PhSe group of the key intermediates ( 15, 16, ent - 15, and ent - 16 ). In connection with this study, 4(5)-(5-aminomethylfuran-2-yl)-1 H -imidazole ( 5 ) was also synthesized starting from d -ribose.",10.1021/jo9910637,1999-10-16,0.6103137883100639
Tetrahedron,A new and efficient one-pot procedure for the synthesis of 2-styrylquinolines,,10.1016/j.tetlet.2008.06.054,2008-06-15,0.6103125787478602
Tetrahedron,"A new titanate/(+)-(1R,2S)-cis-1-amino-2-indanol system for the asymmetric synthesis of (S)-tenatoprazole",,10.1016/j.tetlet.2009.01.111,2009-01-24,0.610303537439257
Journal of Organic Chemistry,New Chiral Benzothiazine Ligand and Its Use in the Synthesis of a Chiral Receptor,"The development of chiral ligands to direct the course and stereoselectivity of many catalytic asymmetric reactions is an important area of interest for many research groups. As part of a program examining the chemistry of 2,1-benzothiazines, we have prepared a new chiral benzothiazine ligand. This ligand can be made in as few as three steps from commercially available starting materials. Presented herein is the synthesis of the ligand along with the synthesis of a chiral molecular receptor that potentially presages a new class of chiral molecular tweezers.",10.1021/jo060175c,2006-03-29,0.6102911524557738
Tetrahedron,Studies in macrolide synthesis: an efficient synthesis of two chiral fragments of erythronolide a,,10.1016/s0040-4039(00)86280-2,1983-01-01,0.6102878063024663
Organic Letters,Dehydrative Fragmentation of 5-Hydroxyalkyl-1<i>H</i>-tetrazoles: A Mild Route to Alkylidenecarbenes,"The development of a mild, base-free method for the generation of alkylidenecarbenes is reported. Treatment of 5-hydroxyalkyl-1H-tetrazoles with carbodiimides generates products arising from the 1,2-rearrangement or [1,5]-C-H bond insertion of a putative alkylidenecarbene. Formation of this divalent intermediate is proposed to occur by way of a tetraazafulvene, which undergoes extrusion of 2 mol of dinitrogen. Details of this methodology, its application to the synthesis of combretastatin A-4, and an improved route to 5-hydroxyalkyl-1H-tetrazoles are described.",10.1021/ol300276p,2012-02-28,0.6102868349261032
Tetrahedron,Studies in marine macrolide synthesis: Stereocontrolled synthesis of the C1C11 and C15C27 subunits of aplyronine A,,10.1016/s0040-4039(98)01191-5,1998-08-01,0.6102803486149387
Tetrahedron,Studies in macrolide synthesis: Stereocontrolled synthesis of a C1C13 segment of concanamycin A,,10.1016/s0040-4039(97)00816-2,1997-06-01,0.6102803486149387
Tetrahedron,Studies in marine macrolide synthesis: Stereocontrolled synthesis of the AB-spiroacetal subunit of spongistatin 1 (altohyrtin A),,10.1016/0040-4039(96)01961-2,1996-11-01,0.6102803486149387
Tetrahedron,Studies towards the synthesis of guanidine alkaloids; synthesis of a tricyclic guanidine from succinimide,,10.1016/0040-4039(95)02258-9,1996-02-01,0.6102803486149387
Tetrahedron,Studies in marine macrolide synthesis: stereocontrolled synthesis of a C21–C34 subunit of the aplyronines,,10.1016/s0040-4039(02)01217-0,2002-08-01,0.6102803486149387
Tetrahedron,Studies in marine macrolide synthesis: A stereocontrolled synthesis of a C17-C32 subunit of scytophycin C.,,10.1016/s0040-4039(00)73994-3,1993-08-01,0.6102803486149387
Tetrahedron,Studies towards the synthesis of obtusenyne. Synthesis of the hexahydrooxonin nucleus,,10.1016/s0040-4039(00)92339-6,1992-01-01,0.6102803486149387
European Journal of Organic Chemistry,Enantioselective Synthesis of the C23–C33 Fragment of Aetheramide A and Its C32 Epimer,"The key aetheramide A intermediate with the natural ( R , R , R ) configuration along with the one having the unnatural ( R , S , R ) configuration was synthesized. The synthesis of both stereoisomers was accomplished by Suzuki coupling of two advanced chiral building blocks: ( R , R )‐ and ( R , S )‐vinylboronates and an ( R )‐iodoalkene. The former was prepared from ( R )‐mandelic acid, and the latter was prepared by enantioselective allylation of 3‐iodoacrylaldehyde.",10.1002/ejoc.201701416,2017-10-13,0.6102767714154435
Organic Process Research & Development,Utilization of a Benzoyl Migration To Effect an Expeditious Synthesis of the Paclitaxel C-13 Side Chain,"A benzoyl migration has been used to remove two steps during the asymmetric dihydroxylation literature route to (2 R,3 S )- N -benzoyl-3-phenylisoserine, the C-13 position side chain of paclitaxel. The modification provides the product as its more desirable methyl ester in similar overall yields with no loss of enantiomeric purity when scaled up to multigram quantities.",10.1021/op970113b,1997-09-01,0.6102705903625908
Journal of Organic Chemistry,"Concise Synthesis of Enantiomers of 4-Aminobutane-1,2,3-triol","A very efficient synthesis of (2R,3S) and (2S,3R)-4-aminobutane-1,2,3-triol has been developed using either d- or l-glucose as the starting material. A key step is the one-pot conversion of an aldehyde to an amide, the scope of which has been extended to include other carbohydrate-derived aldehydes.",10.1021/jo702647n,2008-03-01,0.6102683093500525
Tetrahedron,"The synthesis of a conformationally restrained, combined thromboxane antagonist / synthase inhibitor using an intramolecular ‘Stille’- or ‘Grigg’-palladium-catalysed cyclisation strategy",,10.1016/s0040-4039(00)61429-6,1993-12-01,0.6102518480377108
Synthesis,"Total Synthesis of Daphniphyllum Alkaloids: (+)-Daphlongamine E, (+)-Calyciphylline R, and (–)-10-Deoxydaphnipaxianine A","Abstract Here, we wish to describe our detailed efforts in the total synthesis of three calyciphylline A-type alkaloids, namely (+)-daphlongamine E, (+)-calyciphylline R, and (–)-10-deoxydaphnipaxianine A. Important steps in our approach include a Pt-catalyzed nitrile hydration, a Babler–Dauben rearrangement, a novel selective amide reduction tactic, and an oxidative Nazarov cyclization via an unfunctionalized tertiary divinyl carbinol (TDC).",10.1055/a-2244-1600,2024-01-12,0.610243078973295
European Journal of Organic Chemistry,Enantioselective Synthesis of the Hydroazulene Core of 3α‐Hydroxy‐15‐rippertene,"Abstract As part of a project directed toward the total synthesis of the tetracyclic diterpene 3α‐hydroxy‐15‐rippertene, a constituent of the defense secretion of higher termites, a fast access to two advanced hydroazulene key intermediates has been achieved by starting from (–)‐isopulegol. A regio‐ and diastereoselective formal hydromethallylation and a regioselective ring expansion served as the key steps in the formation of the seven‐membered ring. Completion of the bicyclic title compounds was then achieved by cyclopentene annulation through diastereoselective conjugate addition of organocuprates and subsequent intramolecular aldol condensations.(© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2008)",10.1002/ejoc.200700904,2007-11-20,0.610239227714631
Tetrahedron,"Chiral azole derivatives, 3. Synthesis of the enantiomers of the potent aromatase inhibitor 1-[2-benzofuranyl(4-chlorophenyl)methyl]-1H-imidazole",,10.1016/s0040-4039(99)01569-5,1999-10-01,0.6102237203860322
Synlett,"Synthesis of New Chiral 4,5,6,7-Tetrahydro[1,2,3]triazolo[1,5-<i>a</i>]pyrazines from α-Amino Acid Derivatives under Mild Conditions","A practical and efficient regioselective synthesis of several new chiral 4,5,6,7-tetrahydro[1,2,3]triazolo[1,5-a]pyrazines is described from α-amino acid derivatives following intramolecular ‘click’ reaction as the key step. The method obviates product ­purification; to obtain the pure triazole products, only the solvent needs to be evaporated.",10.1055/s-2007-984537,2007-07-01,0.6102055939946048
Journal of the American Chemical Society,"Chemoenzymatic Total Synthesis of <i>ent</i>-Oxycodone: Second-, Third-, and Fourth-Generation Strategies","Four distinct approaches to ent -oxycodone were designed and accomplished. All rely on the same starting material, the diene diol derived from phenethyl acetate by the whole-cell fermentation with E. coli JM109 (pDTG601A), a strain that overexpresses toluene dioxygenase. The key step in the first-generation approach involves the construction of the C-9/C-14 bond by a SmI 2 -mediated cyclization of a keto aldehyde. The second-generation design relies on the use of the Henry reaction to accomplish this task. In both of these syntheses, Parker’s cyclization was employed to construct the D-ring. The third-generation synthesis provides an improvement over the second in that the nitrogen atom at C-9 is introduced by azidation of the C-9/C-10 olefin, followed by reduction and lactam formation between the C-9 amine and the Fukuyama-type lactone. Finally, the fourth generation takes advantage of the keto–nitrone reductive coupling to generate the C-9/C-14 linkage. The four generations of the total syntheses of ent -oxycodone were accomplished in 13, 18, 16, and 11 operations (19, 23, 24, and 18 steps), respectively. Experimental and spectral data are provided for all new compounds.",10.1021/jacs.9b05033,2019-06-11,0.6102026144071441
Organic Process Research & Development,Preparation of a Corticotropin-Releasing Factor Antagonist by Nucleophilic Aromatic Substitution and Copper-Mediated Ether Formation,"Several synthetic approaches to a corticotropin-releasing factor (CRF) antagonist containing a tetrasubstituted pyridine were evaluated. In particular, nucleophilic aromatic substitutions on 2,4-dichloropyridine derivatives were attempted using 2,6-dimethyl-4-chlorophenol ( 4 ), ( S )-2-aminobutanol ( 7 ), and several sulfur nucleophiles. It was found that a copper-mediated coupling of a phenoxymesylate ( 26 ) was preferred for preparation of the diarylether followed by nucleophilic aromatic substitution to introduce the amine side chain, affording the desired drug candidate ( 1 ) in two steps from the commercially available methyl 2,4-dichloro-6-methylnicotinate ( 2 ).",10.1021/op800266x,2009-01-13,0.6101920048836746
Journal of Organic Chemistry,Enantioselective Synthesis of an Aziridinomitosane and Selective Functionalizations of a Key Intermediate,"An enantioselective synthesis of mitosane core (-)-1 has been achieved. Key steps include a rapid assembly of a key eight-membered-ring intermediate employing ring-closing metathesis. Kinetic resolution of an advanced secondary alcohol was then accomplished by using a peptide-based asymmetric acyl transfer catalyst that was discovered from a parallel screen of catalyst candidates. Optically pure material was then converted to the mitosane core, which was the subject of additional studies on the selective modification to produce several substituted compounds containing a mitosane ring system.",10.1021/jo0269013,2003-02-25,0.6101784423777978
Synthesis,"Convenient Synthesis of 2-Aminonaphthalene-1-thiol and 3-Aminoquinoline-4-thiol and Cyclocondensations to 1,4-Thiazino and 1,4-Thiazepino Derivatives","An improved method for the synthesis of 2-aminonaphthalene-1-thiol and an alternative procedure for the preparation of 3-aminoquinoline-4-thiol are described. From these intermediates some 1,4-thiazepino and 1,4-thiazepino tricyclic derivatives have been prepared",10.1055/s-1992-26191,1992-01-01,0.6101761682223101
Tetrahedron,Intramolecular sulfenyl bromide addition promising a new synthetic route to 9(O)-thiaprostacyclin,,10.1016/s0040-4039(01)83420-1,1977-01-01,0.6101759870153055
Tetrahedron,Intramolecular sulfenyl bromide addition promising a new synthetic route to 9(O)-thiaprostacyclin,,10.1016/s0040-4039(01)94701-x,1978-01-01,0.6101759870153055
Organic Letters,Diastereoselective Synthesis of Pyrrolidines Using a Nitrone/Cyclopropane Cycloaddition:  Synthesis of the Tetracyclic Core of Nakadomarin A,"The synthesis of the tetracyclic core of nakadomarin A is described. The core contains all the heterocycles and the required stereocenters found in the natural product and provides a promising route to the target itself. The strategy utilizes a general, diastereoselective pyrrolidine synthesis that proceeds via a homo 3 + 2 dipolar cycloaddition. The scope of this methodology is also described. [structure: see text]",10.1021/ol0501018,2005-02-01,0.6101725378249997
Organic Letters,Stereodivergent Construction of Aminodiols with a CF<sub>3</sub> Group,"A stereodivergent synthesis of various 2-amino-1,3-diols and 3-amino-1,2-diols from a single intermediate, 2,3-epoxyketones, is described.",10.1021/ol101459a,2010-09-07,0.6101600949222232
Journal of Organic Chemistry,Enantioselective Synthesis of Substituted Pipecolic Acid Derivatives,"Enantiomerically pure 4-piperidones, prepared by asymmetric [4 + 2] Diels−Alder cycloadditon of chiral 2-aminodienes with imines, have been used as starting materials for the synthesis of several derivatives of pipecolic acid. The α-amino acid moiety is obtained after the oxidation of a hydroxy group or a furan ring of a conveniently protected 2-aryl-6-(hydroxymethyl)-4-piperidone. Depending on the starting piperidone and the synthetic strategy, it is possible to obtain d - or l -functionalized pipecolic acid derivatives by a short synthetic procedure. Moreover, a stereoselective epimerization of the α-carbon atom of a particular pipecolate allows for the preparation of both cis - and trans - 6-(hydroxymethyl)pipecolic acids, structures related with dipeptide isosteres.",10.1021/jo9722414,1998-05-23,0.6101539236049432
Journal of Organic Chemistry,Improved Synthesis of a Cyclic Glutamine Analogue Used in Antiviral Agents Targeting 3C and 3CL Proteases Including SARS-CoV-2 M<sup>pro</sup>,"High Resolution Image Download MS PowerPoint Slide An intermediate in the synthesis of numerous antiviral protease inhibitors is the glutamine analogue, (3 S )-pyrrolid-2-one-3-yl- l -alanine. Preparations of compounds based on this pharmacophore are hindered by the lack of a reliably high yielding synthesis of protected forms of this amino acid. We describe an improved scalable route with readily available reagents and facile purification. This methodology employs γ-allylation of dimethyl N -BocGlu, further Boc N-protection, OsO 4 -periodate oxidation, O-Me oxime formation, and RaNi-catalyzed hydrogenolysis with concomitant cyclization under basic conditions.",10.1021/acs.joc.1c01299,2021-08-28,0.610153375683457
Synlett,"Total Synthesis and Stereochemical Confirmation of 2,5-Diaryl-3,4-dimethyltetrahydrofuran Lignans: (+)-Fragransin A<sub>2</sub>, (+)-Galbelgin, (+)-Talaumidin, (-)-Saucernetin and (-)-Verrucosin",A new ring closure to tetrasubstituted tetrahydrofurans from the intramolecular attack of an OMOM ether onto a benzylic mesylate proceeds through a quinonoid intermediate or by direct SN2 displacement. The synthesis of diastereomeric biologically active natural lignans is described utilizing this general methodology.,10.1055/s-2007-968019,2007-02-01,0.6101497864944265
Organic Letters,Synthetic Studies on Borrelidin:  Enantioselective Synthesis of the C1−C12 Fragment,"[structure: see text] An efficient, enantioselective synthesis of the C1-C12 fragment 2 of borrelidin is presented. Construction of the ""skipped"" polymethylene chain of 2 was accomplished by iteration of Myers' alkylation, while formation of the C3 stereocenter was achieved by Roush's asymmetric allylboration methodology.",10.1021/ol034243i,2003-04-10,0.6101433614256091
Journal of Organic Chemistry,"General and Efficient Route for the Synthesis of 3,4-Disubstituted Coumarins via Pd-Catalyzed Site-Selective Cross-Coupling Reactions","Palladium-catalyzed site-selective cross-coupling reactions of 3-bromo-4-trifloxycoumarin or 3-bromo-4-tosyloxycoumarin provide an efficient and facile route for the synthesis of 3,4-disubstituted coumarins, which include 3,4-diarylcoumarins, 3-amino-4-arylcoumarins, and 3-aryl-4-aminocoumarins. The order of reactivity of the (pseudo)halide substituents in the coumarins was found to be 4-OTf > 3-Br > 4-OTs.",10.1021/jo071117+,2007-08-18,0.6101398135593753
European Journal of Organic Chemistry,"A Short and Efficient Synthesis of  (2S,2′R,3′R)-2-(2′,3′-Dicarboxylcyclopropyl)glycine (DCG-IV)","Feist′s acid (5) was used in enantiomerically pure form as starting material for the synthesis of (2S,2′R,3′R)-2-(2′,3′-dicarboxylcyclopropyl)-glycine (DCG-IV) (2). This conformationally restricted analog of L-glutamic acid (L-Glu) 1 is a potent group II mGlu receptor agonist.",10.1002/(sici)1099-0690(199911)1999:11<3131::aid-ejoc3131>3.0.co;2-j,1999-11-01,0.6101367848002857
Organic Letters,First Total Synthesis and Structural Confirmation of Fluvirucinine A<sub>2</sub> via an Iterative Ring Expansion Strategy,"The first asymmetric total synthesis of fluvirucinine A(2) has been accomplished. A key feature of the synthesis is an iterative lactam ring expansion to provide rapid access to the 14-membered lactam skeleton and three stereogenic centers. The excellent remote control of the three stereogenic centers relied on stereoselective amidoalkylation followed by an amide-enolate-induced aza-Claisen rearrangement. In addition, the structure of fluvirucinine A(2) has been completely elucidated by our total synthesis.",10.1021/ol100521v,2010-03-26,0.6101348936265474
Journal of the American Chemical Society,Enantioselective Total Synthesis of (+)- and (−)-Nigellamine A<sub>2</sub>,"The nigellamine alkaloids are dolabellane diterpenes displaying potent lipid metabolism-promoting activity. Total synthesis of (+)- and (-)-nigellamine A2 has been accomplished. Absolute stereochemistry of synthetic nigellamine A2 was established through an intramolecular asymmetric allylic alkylation using a Pd(phosphinooxazoline) catalyst. Other notable transformations include a radical alkynylation, a diastereoselective Nozaki-Hiyama-Kishi cyclization, and a regio- and stereoselective catalytic epoxidation. On the basis of X-ray crystallographic analysis of an optically active intermediate, we have confirmed the assigned absolute stereochemistry of the natural product. Minor modifications of the synthetic sequence outlined here should provide access to the other nigellamine alkaloids.",10.1021/ja061559n,2006-05-23,0.6101174152171249
Tetrahedron,"Functionalized aryllithium intermediates a new route to 3,4-dihydroisoquinolines.",,10.1016/s0040-4039(01)83450-x,1977-01-01,0.6101125409964641
Journal of Organic Chemistry,One-Pot Multistep Bohlmann−Rahtz Heteroannulation Reactions:  Synthesis of Dimethyl Sulfomycinamate,"[reaction: see text] The synthesis of dimethyl sulfomycinamate, the acidic methanolysis product of the sulfomycin family of thiopeptide antibiotics, from methyl 2-oxo-4-(trimethylsilyl)but-3-ynoate is achieved in a 2,3,6-trisubstituted pyridine synthesis that proceeds with total regiocontrol in 13 steps by the Bohlmann-Rahtz heteroannulation of a 1-(oxazol-4-yl)enamine or in 12 steps and 9% yield by three-component cyclocondensation with N-[3-oxo-3-(oxazol-4-yl)propanoyl]serine and ammonia in ethanol.",10.1021/jo048106q,2005-01-22,0.6100852052994142
Organic Letters,Second-Generation Atroposelective Synthesis of KRAS G12C Covalent Inhibitor GDC-6036,"A chromatography-free asymmetric synthesis of GDC-6036 ( 1 ) was achieved via a highly atroposelective Negishi coupling of aminopyridine 5 and quinazoline 6b catalyzed by 0.5 mol % [Pd(cin)Cl] 2 and 1 mol % ( R, R )-Chiraphite to afford the key intermediate ( R a )- 3 . An alkoxylation of ( R a )- 3 with ( S )- N -methylprolinol ( 4 ) and a global deprotection generates the penultimate heterobiaryl intermediate 2 . A controlled acrylamide installation by stepwise acylation/sulfone elimination and final adipate salt formation and crystallization delivered high-purity GDC-6036 ( 1 ).",10.1021/acs.orglett.3c00961,2023-05-10,0.6100833482472285
Organic Letters,Stereoselective Synthesis of the γ-Lactam Hydrolysate of the Thiopeptide Cyclothiazomycin,"[reaction: see text] Bohlmann-Rahtz pyridine synthesis of a chiral nonracemic enamine and thiazolylpropynone gives a terminal-protected pyridine-containing gamma-amino acid in high optical purity in a sequential one-pot multicomponent reaction that proceeds with total control of regiochemistry and with minimal racemization. Further elaboration has established the synthesis of the gamma-lactam acidic hydrolysate of the macrocyclic thiopeptide antibiotic cyclothiazomycin, a selective renin inhibitor, in only four steps and 30% overall yield and has confirmed its structure.",10.1021/ol0485870,2004-08-26,0.610069879695981
Journal of Organic Chemistry,Synthesis of Carbacephems from Serine,"Carbacephems have been synthesized from d -serine by two routes involving construction first of the six-membered ring followed by cyclization to give the bicyclic β-lactam. In one route, alkylation of a lactim ether was accomplished with Ni(Acac) 2 as a catalyst. The desired R stereochemistry at the carbon corresponding to C-6 of the cephem was obtained by stereospecific hydrogenation of a vinylogous carbamate. The second route involved a stereospecific Michael cyclization to give the same C-6 stereochemistry. Closure of a piperidyl β-amino acid intermediate common to both routes was accomplished using a modified Mukaiyama reagent found to be superior in our system to the traditional reagent. The resulting carbacephem core was stereospecifically substituted at C-7 with an ethyl or amino functionality. The ethylated intermediate was transformed into a stable enol triflate useful for the further elaboration of biologically important carbacephems.",10.1021/jo980592s,1998-10-16,0.6100690662168557
Chemical Science,A copper-catalyzed double coupling enables a 3-step synthesis of the quassinoid core architecture,"A cross coupling/S <sub>N</sub> 2′ tandem reaction is described to construct the polycyclic core architecture of the quassinoids, a fascinating class of degraded triterpenes with potent anticancer activity.",10.1039/c8sc03835j,2018-10-29,0.6100622404673378
Synthesis,De Novo Asymmetric Synthesis of Protected 5-O-Carbamoylpolyoxamic Acid,"All articles of this category The synthesis of 5- O -carbamoylpolyoxamic acid from a non carbohydrate precursor was achieved in 12 steps and 7% yield starting from chiral α , β -epoxyaldehyde readily available from cis -2-butene-1,4-diol. The main steps concern the Sharpless asymmetric epoxidation of a suitable chosen allylic alcohol, the use of thiazolyl group for carbon homologation, the stereo- and regioselective opening of the epoxide and the transformation of the primary alcohol to the acid functionality of the final product. amino acids - antifungal agents - asymmetric synthesis - epoxide - azide",10.1055/s-2000-7114,2000-01-01,0.6100604893805153
Tetrahedron,A synthetic route to enediyne-bridged amino acids,,10.1016/j.tetlet.2007.05.016,2007-05-11,0.610045735182748
Synlett,"A Stable Synthetic Equivalentof 2,3-Dihydropyridine","We introduce a synthetic procedure of 2,3-dihydropyridine derivative from its stable synthetic equivalent. The synthesis of a chiral 2,3-dihydropyridine derivative in a high yield and the unique mechanism of the unmasking step are described.",10.1055/s-2008-1078056,2008-09-12,0.6100388100597853
Synlett,"An Organocatalytic Approach to Enantiopure 2,6-Disubstituted Tetrahydropyranols","A method is described for the synthesis of cis-2,6-disubstituted tetrahydropyranols related to ring A of ambruticin S. An organocatalytic and metal-free aldol condensation was utilized as a key step between appropriate carbonyl-containing precursors resulting in high diastereoselection and 24% overall yield for seven steps.",10.1055/s-0029-1219354,2010-01-26,0.610028157966015
Organic Letters,Studies toward the Total Synthesis of Diterpene Antibiotic Guanacastepene A:  Construction of the Hydroazulenic Core,"[reaction: see text] As a part of studies aimed toward the total synthesis of biologically important natural product guanacastepene A of contemporary interest, a new and concise route to a fully functionally endowed hydroazulenic core is delineated. The strategy involves the building of the requisite stereochemical features on a endo-tricyclo[5.2.1.0(2,6)]decane matrix and excision of the five-membered ring through a retro-Diels-Alder reaction. Generation of the seven-membered ring to access the hydroazulenic framework was achieved employing ring closure metathesis (RCM) reaction as the key step.",10.1021/ol017098m,2002-03-07,0.6100218168654853
Journal of Organic Chemistry,Synthesis of (<i>S</i>)-7-Amino-5-azaspiro[2.4]heptane via Highly Enantioselective Hydrogenation of Protected Ethyl 1-(2-Aminoaceto)cyclopropanecarboxylates,"Highly effective asymmetric hydrogenation of protected ethyl 1-(2-aminoaceto)cyclopropane carboxylates in the presence of [RuCl(benzene)(S)-SunPhos]Cl was realized, and high enantioselectivities (up to 98.7% ee) were obtained. This asymmetric hydrogenation provides a key intermediate for the enantioselective synthesis of (S)-7-amino-5-azaspiro[2.4]heptane moiety of quinolone antibacterial agents.",10.1021/jo2002165,2011-03-17,0.6100202511012419
Journal of Organic Chemistry,Enzyme-Assisted Asymmetric Total Synthesis of (−)-Podophyllotoxin and (−)-Picropodophyllin,"Described is the first catalytic, asymmetric synthesis of (-)-podophyllotoxin and its C(2)-epimer, (-)-picropodophyllin. Asymmetry is achieved via the enzymatic desymmetrization of advanced meso diacetate 20, through PPL-mediated ester hydrolysis. A second key feature of the synthesis is the strategically late introduction of the highly oxygenated natural ring E through an arylcopper species. The successful implementation of this approach augers well for the introduction of other functionalized rings E for future SAR work. The synthesis begins from piperonal, which is fashioned into isobenzofuran (IBF) precursor 14 in three steps (bromination, acetalization, and halogen-metal exchange/hydroxymethylation). Interestingly, treatment of 14 with HOAc in commerical dimethyl maleate (contains 5% dimethyl fumarate) leads to a nearly equimolar mixture of fumarate- (15) and maleate-IBF Diels-Alder adducts (16 and 17), indicating that IBF 11 reacts about 15 times faster with dimethyl fumarate than with dimethyl maleate. With scrupulously pure dimethyl maleate a 2.8:1 endo:exo mixture of maleate DA adducts is still obtained. On the other hand, the desired meso diester 16 is obtained pure and in nearly quantitative yield by employing neat dimethyl acetylene dicarboxylate as the dienophile, followed by catalytic hydrogenation. Reduction (LiAlH(4)) of 16 provides meso diol 19, which is then treated with Ac(2)O, BzCl, and PhCH(2)COCl to provide the corresponding meso diesters, 20-22. Screening of these meso benzoxabicyclo[2.2.1]heptyl substrate candidates across a battery of acyl transfer enzymes leads to an optimized match of diacetate 20 with PPL. Even on 10-20 g scales, asymmetry is efficiently introduced here, yielding the key chiral intermediate, monoacetate 25 (66% isolated yield, 83% corrected yield, 95% ee). Protecting group manipulation and oxidation (Swern) provide aldehyde 27b, which undergoes efficient retro-Michael ring opening to produce dihydronaphthalene 30, in which the C(3) and C(4) stereocenters are properly set. Following several unsuccessful approaches to the intramolecular delivery of ring E (via Claisen rearrangement, Heck-type cyclization, or radical cyclization), a highly diastereoselective, intermolecular conjugate addition of the arylcopper reagent derived from (3,4,5-trimethoxy)phenylmagnesium bromide and CuCN to acyl oxazolidinone 50 was developed (85% yield, only the required alpha-stereochemistry at C(1) is observed). The conjugate addition product is converted to (-)-picropodophyllin in two steps (lactonization, SEM deprotection) or to (-)-podophyllotoxin, in three steps, through the introduction of a C(2)-epimerization step, under Kende conditions, prior to the final conjugate addition.",10.1021/jo991582+,2000-01-14,0.6100116252207025
Journal of Organic Chemistry,Regioselective Enolization and Alkylation of 4-Oxo-<i>N</i>-(9-phenylfluoren-9-yl)proline:  Synthesis of Enantiopure Proline−Valine and Hydroxyproline−Valine Chimeras,"The regioselective enolization of 4-oxo- N -(9-phenylfluoren-9-yl)proline benzyl ester ( 5 ) followed by alkylation with different alkyl halides has been used to synthesize a variety of β-alkylproline derivatives. In particular, enolization of 5 with 400 mol % of KN(SiMe 3 ) 2 and alkylation with iodomethane provided 3,3-dimethyl-4-oxo- N -(9-phenylfluoren-9-yl)proline benzyl ester ( 7a ) in excellent yield. Subsequent hydride reduction of ketone 7a and protecting group exchange by hydrogenation in the presence of di- tert -butyl dicarbonate provided enantiopure (2 S,4R )- and (2 S,4S )-3,3-dimethyl-4-hydroxy- N -(BOC)prolines 2 . Hydroxyproline−valine chimeras (2 S,4R )- and (2 S,4 S )- 2 are each synthesized from hydroxyproline in six steps and 27% respective overall yield. Deoxygenation of 3,3-dimethyl-4-hydroxy- N -(9-phenylfluoren-9-yl)proline benzyl esters 9 via their conversion to xanthates 10 followed by tributylstannane-mediated reduction provided 3,3-dimethyl- N -(9-phenylfluoren-9-yl)proline benzyl ester ( 11 ) in excellent yield. Hydrogenation of 11 with Pearlman's catalyst in the presence of di- tert -butyl dicarbonate then furnished (2 S )-3,3-dimethyl- N -(BOC)proline ( 1 ) in the last step of an eight-step synthesis (41% overall yield) from hydroxyproline. Both proline−valine and hydroxyproline−valine chimeras 1 and 2 were designed to serve as tools for studying the conformational requirements of biologically active peptides.",10.1021/jo9514984,1996-01-01,0.6100104484552501
Organic Letters,Total Synthesis of the Marine Macrolide Amphidinolide F,"A new and efficient convergent approach toward the synthesis of amphidinolide F is described through the assembly of three fragments. The two trans-tetrahydrofurans were built by a diastereoselective C-glycosylation with titanium enolate of bulky N-acetyloxazolidinethiones. The side chain was inserted by a Liebeskind-Srogl cross-coupling reaction. A sulfone condensation/desulfonylation sequence, a Stille cross-coupling, and a macrolactonization were applied to connect the fragments.",10.1021/acs.orglett.8b01020,2018-05-15,0.6100091124826824
Tetrahedron,A novel method for the synthesis of chiral sulfonated phosphines,,10.1016/s0040-4039(96)02407-0,1997-02-01,0.6100072649849755
Organic Letters,Dichloroketene−Chiral Olefin-Based Approach to Pyrrolizidines:  Highly Stereocontrolled Synthesis of (+)-Amphorogynine A,"[reaction: see text] A highly stereoselective route to (+)-amphorogynine A, a novel pyrrolizidine recently isolated from the New Caledonian plant Amphorogynine spicata, has been realized. The key step in the approach is a diastereoselective [2 + 2] dichloroketene-chiral enol ether cycloaddition (dr >or= 93:7) to access a dichlorocyclobutanone intermediate, which is converted into the alkaloid natural product via a pyrrolidinone derivative.",10.1021/ol034369f,2003-04-24,0.6100021550118733
Organic Letters,Total Syntheses of Plocabulin and Its C2-Analogues,"Plocabulin is a structurally unique marine natural product with potent antitumor activity, making it a promising candidate for the development of antibody-drug conjugates (ADCs). However, its extremely low natural abundance has limited further research and therapeutic exploration. In this study, we present a convergent synthetic strategy for plocabulin and its C2-analogues. Our approach enabled the synthesis of 1.23 g of plocabulin through a longest linear sequence of 12 steps and a total of 24 steps, achieving an overall yield of 19.7%.",10.1021/acs.orglett.5c01284,2025-04-30,0.6099946701054295
Tetrahedron,"A novel, iterative, stereoselective route to the synthesis of axially linked 2-deoxysaccharides",,10.1016/0040-4039(91)80508-4,1991-12-01,0.6099918803334021
Journal of Organic Chemistry,Synthesis of (+)-Spirolaxine Methyl Ether,"A short and efficient synthesis of (+)-spirolaxine methyl ether, a metabolite of the fungus Sporotrichum laxum with inhibitory activity against Helicobacter pylori, is described. The synthesis has been carried out by a Prins cyclization, to obtain the [6,5]-spiroketal system, and a Wadsworth-Emmons condensation, applied for the installation of the polymethylene chain on the phthalide moiety.",10.1021/jo060839i,2006-07-11,0.6099906952169731
Tetrahedron,"Synthetic studies of trichothecenes, an enantioselective synthesis of a C-ring precursor of anguidine",,10.1016/s0040-4039(00)88700-6,1982-01-01,0.6099858058653657
Organic Letters,"Rh(III)-Catalyzed C–H Annulation of Alkenyl- or Arylimidazoles and (Hetero)cyclic 1,3-Dicarbonyl Compounds: A Rapid Access to Imidazo-Fused Polycyclic Compounds","A novel strategy for the synthesis of imidazo-fused polycyclic compounds under mild, base-free, and silver-free conditions by a rhodium(III)-catalyzed C-H annulation of alkenyl or arylimidazoles and (hetero)cyclic 1,3-dicarbonyl compounds is reported here. Such a step-economic protocol features the selective cleavage of two different C-H bonds in one step, featuring easy operation, readily available starting materials, gram-scale synthesis, broad functional group tolerance, and no requirement to presynthesize carbene precursors. Notably, the synthetic potential is showcased by the structural modification of drug and the highly step-economic synthesis of Janus kinase inhibitor in only three steps with a satisfactory 26% total yield (previous method: in nine steps with 0.6% yield).",10.1021/acs.orglett.2c01315,2022-06-07,0.6099852640398151
Organic Letters,Total Synthesis of Pericoannosin A,"The first total synthesis of pericoannosin A (1) containing 15 steps in the longest linear sequence with an overall yield of 5.5% is reported. The hybrid peptide-polyketide was isolated from the endophytic fungus Periconia sp. F-31 and bears a unique tricyclic core structure. The key steps are a glycolate aldol reaction and a Diels-Alder reaction utilizing an Evans auxiliary for controlling the stereochemistry. Furthermore, a late-stage equilibration was employed.",10.1021/acs.orglett.8b01768,2018-07-13,0.6099806722884825
Tetrahedron,Biomimetic transformations of 2-aminoimidazole into zoanthoxanthins: Exposing a potential biogenic missing link,A one-step synthesis of the nitrogenous marine pigment parazoanthoxanthin A (1a) and related pseudozoanthoxanthin A (2a) from 2-aminoimidazole is described. The key step involves hydroxyalkylation of the C3N3 heterocycle with acetaldehydes and pyruvic acid.,10.1016/s0040-4039(00)60090-4,1992-07-01,0.6099649255022833
European Journal of Organic Chemistry,Synthesis of the AB‐Ring Pyranolactone Substructure of Granaticin A,"Abstract A synthesis of the AB‐ring substructure of granaticin A was developed. The pyranolactone moiety was stereoselectively accessed by Sharpless asymmetric dihydroxylation and subsequent oxa‐Pictet–Spengler cyclization. The use of BF 3 · OEt 2 resulted in the formation of the cis pyranolactone, whereas the combination of BF 3 · OEt 2 with trifluoroacetic acid led to the trans isomer. The resulting hydroquinones were cleaved selectively by ozonolysis to dicarboxylic acids. An aryl Grignard reagent could be regioselectively added to unsymmetrical anhydrides. As an alternative strategy for the construction of the B‐ring, a benzyne–furan cycloaddition could be established.",10.1002/ejoc.201201279,2012-10-30,0.609963046571563
Tetrahedron,An anionic 3+2 cyclization-elimination route to cyclopentenes,,10.1016/s0040-4039(00)85360-5,1986-01-01,0.6099595137933489
Synlett,Synthesis of a Highly Functionalised Azepine via a New TBSOTf-Mediated Cyclisation of a Terminal Formamide,The synthesis of a highly functionalised azepine which can be further derivatised by common chemical transformations is described herein. The present synthesis comprises high-yielding reaction steps and features a new method for the synthesis of azepines via TBSOTf-mediated cyclisation of terminal formamides.,10.1055/s-2007-967942,2007-02-01,0.6099577702798815
Synlett,Novel Synthesis of Fused Indoles by the Palladium-Catalyzed Cyclization of<i>N</i>-Cycloalkenyl-<i>o</i>-haloanilines,A new palladium-catalyzed cyclization of N-alkenyl-o-haloanilines with selective isomerization of a double bond followed by 5-endo cyclization was developed and used to synthesize fused indoles.,10.1055/s-2004-820039,2004-01-01,0.6099513901769644
Organic Letters,Stereoselective Synthesis of F-Ring Saturated Estrone-Derived Inhibitors of Hedgehog Signaling Based on Cyclopamine,Previous work in this laboratory established that the readily available F-ring aromatic analog of cyclopamine is a highly potent inhibitor of Hedgehog signaling. The synthesis and biological evaluation of two F-ring saturated analogs that are more potent than the F-ring aromatic structure are reported.,10.1021/ol2017966,2011-08-15,0.6099430766665381
Organic Letters,Enantioselective Ir-Catalyzed Hydrogenation of Terminal Homoallyl Sulfones: Total Synthesis of (−)-Curcumene,"A novel methodology for the preparation of chiral methyl benzylic compounds is reported. Terminal homoallyl sulfones were prepared from homoallyl alcohols, which are easily accessible through the recently reported Lewis acid isomerization of oxetanes. The iridium-catalyzed asymmetric hydrogenation of homoallylic sulfones afforded γ-chiral sulfones with excellent enantioselectivities (up to 98% ee). The synthetic potential of this novel methodology was demonstrated by the total synthesis of ( R )-(−)-curcumene.",10.1021/acs.orglett.3c00181,2023-03-01,0.6099326779699398
Journal of Organic Chemistry,Asymmetric Synthesis and Absolute Configuration of Streptophenazine G,"The asymmetric synthesis of the antibacterial natural product, streptophenazine G, has been achieved by employing asymmetric alkylation and asymmetric aldol reactions using chiral oxazolidinones as the key steps. The originally proposed structure for streptophenazine G has been revised, and its absolute configuration has been determined to be 1'S,2'R,6'S. The asymmetric total synthesis of 6'-epi-streptophenazine G is also described.",10.1021/jo202642a,2012-03-21,0.609928587055046
Journal of Organic Chemistry,A Straightforward Stereoselective Synthesis of <scp>d</scp>- and <scp>l</scp>-5-Hydroxy-4-hydroxymethyl-2-cyclohexenylguanine,"A novel and facile synthesis of 5-hydroxy-4-hydroxymethyl-2-cyclohexenylguanine 1 is described. The key steps involve a Diels-Alder reaction of ethyl (2E)-3-acetyloxy-2-propenoate 2 as dienophile with Danishefsky's diene 3 to build up the six-membered ring skeleton, a Fraser-Reid reductive rearrangement of the adduct using LiAlH(4), and base-moiety introduction using a Mitsunobu reaction. Optically pure D- and L-1 were obtained via resolution of intermediate 7 with (R)-(-)-methylmandelic acid. The synthetic procedure toward racemic 1 consists of only five steps and has proven to be highly efficient toward the synthesis of cyclohexenyl nucleosides.",10.1021/jo015924z,2001-11-13,0.6099276631519451
Angewandte Chemie International Edition,Total Synthesis of (+)‐Rubriflordilactone A,"Two enantioselective total syntheses of the nortriterpenoid natural product rubriflordilactone A are described, which use palladium- or cobalt-catalyzed cyclizations to form the CDE rings, and converge on a late-stage synthetic intermediate. These key processes are set up through the convergent coupling of a common diyne component with appropriate AB-ring aldehydes, a strategy that sets the stage for the synthetic exploration of other members of this family of natural products.",10.1002/anie.201506366,2015-09-02,0.6099207875942665
Organic Letters,"Total Synthesis of Lyconesidine B, a <i>Lycopodium</i> Alkaloid with an Oxygenated, Amine-Type Fawcettimine Core","This report describes the total synthesis of the complex, oxygenated tetracyclic alkaloid, lyconesidine B. The key synthetic challenge involves diastereoselective generation of a decahydroquinoline ring with a quaternary carbon at the angular position via domino cyclopropanation, ring-opening, and reduction. Another crucial step is the domino ene-yne metathesis involving a quaternary ammonium ion, leading to the construction of a decahydroazaazulen framework.",10.1021/acs.orglett.0c03816,2020-12-16,0.6099200838116025
Journal of Organic Chemistry,Total Synthesis of (−)-Lepadiformine A via Stereo-convergent Tsuji–Trost Cyclization,A concise synthesis of (−)-lepadiformine A was achieved using a readily available ( S )-pyroglutaminol derivative. This approach involves a Brønsted acid-catalyzed cyclization of N -acyliminium ions using diene and acetic acid for the construction of the azaspiro ring system and a stereoconvergent Tsuji–Trost cyclization to generate a substituted piperidine scaffold with excellent diastereoselectivity.,10.1021/acs.joc.5c00921,2025-06-14,0.6099178055976155
Organic Process Research & Development,One-Pot Process for Synthesis of Nalbuphine Hydrochloride and Impurity Control Strategy,"An improved kilogram-scale process of synthesis of nalbuphine was developed by investigating the critical parameters. Ten process-related impurities were identified, of which the source and control strategy was elucidated. Moreover, tetramethylammonium triacetoxyborohydride (Me 4 NBH(OAc) 3 ) was developed to reduce the imine and ketone in one pot. As a result, 6-β-epimer was significantly controlled to only 0.08% in the crude nalbuphine. The improved process was robust at kilogram scale in 60.4% overall yield with 99.95% high-performance liquid chromatography (HPLC) purity.",10.1021/acs.oprd.0c00321,2020-08-07,0.6099056420852045
Organic Letters,"One-Pot, Pd-Catalyzed Synthesis of <i>trans</i>-Dihydrobenzofurans from <i>o</i>-Aminophenols",An efficient and facile synthesis of trans-dihydrobenzofurans has been accomplished from o-aminophenols and phenylpropenes via a novel (one-pot) diastereoselective Pd-catalyzed oxyarylation reaction. The development and optimization of this method is described.,10.1021/ol100433z,2010-03-25,0.6099008338700093
Journal of the American Chemical Society,Total Synthesis of Kadcoccinic Acid A Trimethyl Ester,"The first total synthesis of the trimethyl ester of kadcoccinic acid A is described. The central structural element of our synthesis is a cyclopentenone motif that allows the assembly of the natural product skeleton. A gold(I)-catalyzed cyclization of an enynyl acetate led to efficient construction of the cyclopentenone scaffold. In this step, optimization studies revealed that the stereochemistry of the enynyl acetate dictates regioisomeric cyclopentenone formation. The synthesis further highlights an efficient copper-mediated conjugate addition, merged with a gold(I)-catalyzed Conia-ene reaction to connect the two fragments, thereby forging the D-ring of the natural product. The synthetic strategy reported herein can provide a general platform to access the skeleton of other members of this family of natural products.",10.1021/jacs.1c05521,2021-07-29,0.609892792252861
Organic Process Research & Development,"Cross-Coupling Methods for the Large-Scale Preparation of an Imidazole−Thienopyridine:  Synthesis of [2-(3-Methyl-3H-imidazol-4-yl)- thieno[3,2-<i>b</i>]pyridin-7-yl]-(2-methyl-1H-indol-5-yl)-amine","The multihundred-gram synthesis of [2-(3-methyl-3H-imidazol-4-yl)-thieno[3,2- b ]pyridin-7-yl]-(2-methyl-1H-indol-5-yl)-amine ( 1 ) is described utilizing a Stille cross-coupling of an iodothienopyridine ( 3 ) with 5-(tributylstannyl)-1-methylimidazole ( 11 ). Several cross-coupling methods were evaluated for the conversion of thienopyridine 3 to imidazole−thienopyridine 2, but only two were effective: the Stille coupling and a Negishi cross-coupling of the organozinc reagent derived from 2-( tert -butyldimethylsilyl)-1-methylimidazole and iodothienopyridine ( 3 ). The latter procedure worked well on laboratory scale (<50 g), but was capricious upon scale-up. The issues with scale-up of an organostannane reagent are discussed, including control and analysis of organotin levels.",10.1021/op0340457,2003-08-01,0.6098782667449282
Journal of the American Chemical Society,Synthesis of (−)-PNU-286607 by Asymmetric Cyclization of Alkylidene Barbiturates,"PNU-286607 is the first member of a promising, novel class of antibacterial agents that act by inhibiting bacterial DNA gyrase, a target of clinical significance. Importantly, PNU-286607 displays little cross-resistance with marketed antibacterial agents and is active against methicillin-resistant staphylococcus aureus (MRSA) and fluoroquinoline-resistant bacterial strains. Despite the apparent stereochemical complexity of this unique spirocyclic barbituric acid compound, the racemic core is accessible by a two-step route employing a relatively obscure rearrangement of vinyl anilines, known in the literature as the ""tert-amino effect."" After a full investigation of the stereochemical course of the racemic reaction, starting with the meso cis-dimethylmorpholine, a practical asymmetric variant of this process was developed.",10.1021/ja808014h,2009-03-04,0.6098733236507435
Tetrahedron,Formal synthesis of nitidine through palladium-catalyzed isocoumarin synthesis,,10.1016/0040-4039(95)02059-4,1995-12-01,0.6098628904246243
Synlett,"Synthesis of Vinylsulfone Derivativesof Sugars: An Easy Preparation of (2<i>R</i>,3<i>S</i>,4<i>E</i>)-5-Benzenesulfonyl-2,3-<i>iso</i>-propylidene-dioxy-pent-4-en-1-yl-tosylate","A two-step procedure for the synthesis of (2R,3S,4E)-5-benzenesulfonyl-2,3-isopropylidene-dioxypent-4-en-1-yl-tosylate is described. The method involves the addition of lithio(phenylsulfonyl)methane to 2,3-O-iso-propylidene-d-erythronolactol and treatment of the resulting diols with tosyl chloride.",10.1055/s-2003-38356,2003-01-01,0.6098522157246555
Journal of Organic Chemistry,Stereoselective Synthesis of Nonpsychotic Natural Cannabidiol and Its Unnatural/Terpenyl/Tail-Modified Analogues,"Here, we report a three-step concise and stereoselective synthesis route to one of the most important phytocannabinoids, namely, (−)-cannabidiol (-CBD), from inexpensive and readily available starting material R -(+)-limonene. The synthesis involved the diastereoselective bifunctionalization of limonene, followed by effective elimination leading to the generation of key chiral p -mentha-2,8-dien-1-ol. The chiral p -mentha-2,8-dien-1-ol on coupling with olivetol under silver catalysis provided regiospecific (−)-CBD, contrary to reported ones which gave a mixture. The newly developed approach was further extended to its structural analogues cannabidiorcin and other tail/terpenyl-modified analogues. Moreover, its opposite isomer (+)-cannabidiol was also successfully synthesized from S -(−)-limonene.",10.1021/acs.joc.1c02571,2022-03-15,0.6098447814434669
Tetrahedron,Synthesis of the optically active key intermediate of FR901483,,10.1016/j.tetlet.2010.05.089,2010-06-03,0.6098260268733984
Synlett,Convenient Synthesis of 3-(S)-Amino-γ-butyrolactone,"An efficient two step conversion of N-t-Boc-L-aspartic acid β-benzyl ester to enantiopure 3-(S)-amino-γ-butyrolactone is described. In this route, chemoselective reduction of the α-carboxylic group in the starting material via a mixed anhydride with NaBH4 afforded the corresponding alcohol in 95% yield without any loss of the optical purity. Subsequent acidic hydrolysis of the N-protected β-amino alcohol not only deprotected the amino group, but also produced the desired γ-lactone in 98% yield with complete retention of the optical activity.",10.1055/s-2002-32597,2002-01-01,0.609824618380302
Journal of Organic Chemistry,Stereoselective Synthesis of Novel Highly Substituted Isochromanone and Isoquinolinone-Containing Exocyclic Tetrasubstituted Alkenes,An efficient synthetic route toward the synthesis of highly substituted arylethylidene-isoquinolinones/isochromanones is reported. The tandem carbopalladation/Suzuki-Miyaura coupling sequence stereoselectively provided various functionalized polycyclic compounds in moderate to excellent yields.,10.1021/jo802729s,2009-02-05,0.6098221826946303
Angewandte Chemie International Edition,Total Synthesis of (±)‐Haliclonacyclamine C,"First in its class: The synthesis of the tetracyclic alkylpiperidine marine alkaloid (±)-haliclonacyclamine C has been completed, with a longest linear sequence of 24 steps. The key transformations are the stereoselective hydrogenation of an unsaturated macrocyclic bis(piperidine) and a ring-closing alkyne metathesis reaction.",10.1002/anie.200905732,2010-02-02,0.6098185003449802
Angewandte Chemie International Edition,Total Synthesis of Luzopeptin E2,The self-assembly of the 32-membered macrocycle of luzopeptin E2 (1) has been accomplished by cyclodimerization of a terminally unprotected pentapeptide monomer. This is the key step of the first total synthesis of this macrocyclic antitumor decadepsipeptide with probable anti-HIV efficacy.,10.1002/1521-3773(20000717)39:14<2493::aid-anie2493>3.0.co;2-5,2000-07-17,0.6098142087277783
Journal of the American Chemical Society,Total Synthesis of (±)-Aspidophylline A,"We report the total synthesis of (±)-aspidophylline A, one of many complex furoindoline-containing alkaloids that has not been synthesized previously. Our route features a number of key transformations, including a Heck cyclization to assemble the [3.3.1]-bicyclic scaffold as well as a late-stage interrupted Fischer indolization to install the furoindoline and construct the natural product's pentacyclic framework.",10.1021/ja203227q,2011-05-09,0.6098102565218669
European Journal of Organic Chemistry,A Chemoenzymatic Approach to the Stereocontrolled Synthesis of the C1–C11 fragment of (+)‐Peloruside A,"Abstract A highly efficient and diastereoselective synthesis of the C1–C11 fragment of the marine natural product (+)‐peloruside A has been developed. Through enzymatic desymmetrization of diethyl 3‐hydroxyglutarate with lipase B from Candida antarctica a large‐scale access to enantiomerically highlyenriched starting material was achieved. Subsequent stereogenerating key steps utilized in the synthesis were a Sharpless asymmetric dihydroxylation and a doubly diastereoselective Mukaiyama aldol reaction to set up thestereogenic centers at C2, C3, C5, C7 and C8 with correct absolute configuration.",10.1002/ejoc.201000369,2010-05-24,0.6098060504626641
Tetrahedron,"A practical synthesis of 2-amino-2′-hydroxy-1,1′-binaphthyl (NOBIN)",,10.1016/s0040-4039(02)01674-x,2002-09-01,0.6098020384935208
Journal of Organic Chemistry,Multicomponent Synthesis of Fused Benzimidazolopiperazines,"We present a novel protocol for the efficient synthesis of fused benzimidazolo piperazines starting from a four-component Ugi-Smiles reaction and a subsequent three-step cascade involving an acid-catalyzed cyclization, an intramolecular reductive cyclization, and an oxidation.",10.1021/jo200397m,2011-04-12,0.6097932126152777
Tetrahedron,Synthetic studies towards phomactin A. Concise synthesis of the novel tricyclic furanochroman system,,10.1016/0040-4039(95)02148-5,1996-01-01,0.6097654964090806
Organic Letters,Synthesis of Mesodiphenylhelianthrene from 1-Aminoanthraquinone and the Structural Elucidation of Its Endoperoxide Species after Irradiation,"A safe, five-step synthetic route to yield the reliable chemical actinometer, mesodiphenylhelianthrene ( MDH ), is reported from a commercially available compound. Full characterization of the intermediates of the synthetic route and the final product MDH are presented together with four crystal structures of intermediates and MDH . The usage of the actinometer is described, and finally, the structure of the endoperoxide species ( MDHPO ), which is formed after irradiation of MDH, has been elucidated experimentally and theoretically.",10.1021/acs.orglett.2c01758,2022-07-18,0.6097635227293591
Journal of Organic Chemistry,Asymmetric Synthesis of <i>anti-</i>Aldol Segments via a Nonaldol Route: Synthetic Applications to Statines and (−)-Tetrahydrolipstatin,"An asymmetric synthesis of anti-aldol segments via a nonaldol route is described. The strategy involves a highly diastereoselective synthesis of functionalized tetrahydrofuran derivatives from optically active 4-phenylbutyrolactone. Treatment of the tetrahydrofuran derivatives with a Lewis acid and acetic anhydride provided the corresponding ring-opened styrene derivatives. Oxidative cleavage of the styrene derivatives provided access to the anti-aldol segments. The utility of this methodology was demonstrated by the synthesis of statine derivatives and pancreatic lipase inhibitor, (-)-tetrahydrolipstatin.",10.1021/jo900642f,2009-05-13,0.6097594591034939
Tetrahedron,Multivalent calixarene-based C-fucosyl derivative: a new Pseudomonas aeruginosa biofilm inhibitor,,10.1016/j.tetlet.2011.08.142,2011-09-01,0.609755826813224
Synthesis,Asymmetric Synthesis of Synargentolide A and Its 3-Epimer Using the RAMP-Hydrazone Methodology,"Synargentolide A was synthesized in 11 steps starting from the commercially available 2,2-dimethyl-1,3-dioxan-5-one, employing the SAMP/RAMP-methodology via an α,α′-bis-alkylation to generate the first two stereogenic centers with virtually complete asymmetric induction (de, ee >99%). After the asymmetric synthesis of the triol fragment of the molecule, the δ-lactone moiety was constructed using an asymmetric allylation, esterification, and ring-closing metathesis sequence.",10.1055/s-0032-1316865,2013-03-07,0.6097459040612364
Tetrahedron,Synthesis of leukotrienes - new synthesis of natural leukotriene A4,,10.1016/s0040-4039(01)82844-6,1981-01-01,0.6097413550015854
Journal of Organic Chemistry,Efficient Method for Synthesis of Angucyclinone Antibiotics via Gold-Catalyzed Intramolecular [4 + 2] Benzannulation:  Enantioselective Total Synthesis of (+)-Ochromycinone and (+)-Rubiginone B<sub>2</sub>,"[reaction: see text] An efficient synthetic approach to angucyclinone antibiotics, (+)-ochromycinone and (+)-rubiginone B(2), is reported. The key step involves the facile formation of 2,3-dihydrophenantren-4(1H)-one skeleton, an important framework of angucyclinone natural products, by using gold-catalyzed intramolecular [4 + 2] benzannulation reaction.",10.1021/jo051444m,2005-09-27,0.6097389043361723
Angewandte Chemie International Edition,Synthesis of Pentaantennary N‐Glycans with Bisecting GlcNAc and Core Fucose,Always use protection? The omission of a single protecting group led to the convergent synthesis of the highly branched dodecasaccharide N-glycan that contains two neighboring tetrasubstituted mannoside groups. A serendipitous finding led to the identification of the key protecting group in oligosaccharide building blocks for the optimized synthesis of N-glycans.,10.1002/anie.200604788,2007-04-20,0.6097251049994857
European Journal of Organic Chemistry,"Iron‐Mediated Total Synthesis of 2,7‐Dioxygenated Carbazole Alkaloids","Abstract We describe the efficient iron‐mediated total synthesis of clausine O, clausine H (clauszoline‐C) and anti‐HIV active 7‐methoxy‐ O ‐methylmukonal and clausine K (clauszoline‐J). Consecutive C–C and C–N bond formations between 3‐methoxy‐4‐methylaniline and a cyclohexadienyliumiron complex salt afforded 2,7‐dimethoxy‐3‐methylcarbazole, which served as common intermediate en route to the four alkaloids.",10.1002/ejoc.201201251,2012-11-21,0.6097158741425911
Journal of Organic Chemistry,"Synthesis of Chiral 1,2-Amino Alcohol-Containing Compounds Utilizing Ruthenium-Catalyzed Asymmetric Transfer Hydrogenation of Unprotected α-Ketoamines","Herein, we disclose a facile synthetic strategy to access an important class of drug molecules that contain chiral 1,2-amino alcohol functionality utilizing highly effective ruthenium-catalyzed asymmetric transfer hydrogenation of unprotected α-ketoamines. Recently, the COVID-19 pandemic has caused a crisis of shortage of many important drugs, especially norepinephrine and epinephrine, for the treatment of anaphylaxis and hypotension because of the increased demand. Unfortunately, the existing technologies are not fulfilling the worldwide requirement due to the existing lengthy synthetic protocols that require additional protection and deprotection steps. We identified a facile synthetic protocol via a highly enantioselective one-step process for epinephrine and a two-step process for norepinephrine starting from unprotected α-ketoamines 1b and 1a, respectively. This newly developed enantioselective ruthenium-catalyzed asymmetric transfer hydrogenation was extended to the synthesis of many 1,2-amino alcohol-containing drug molecules such as phenylephrine, denopamine, norbudrine, and levisoprenaline, with enantioselectivities of >99% ee and high isolated yields.",10.1021/acs.joc.4c00045,2024-04-22,0.6097036805510124
Synthesis,"Use of (Z)-β-(2-Fluorobenzenesulfonyl)vinylamines as Novel Synthons in the Synthesis of 1,4-Benzothiazine Derivatives","A novel synthetic route for arylated 1,4-benzothiazine derivatives has been developed. This method utilizes a key intramolecular nucleophilic aromatic substitution step of the corresponding ( Z )-β-(2-fluorobenzenesulfonyl)vinylamine intermediate to construct the benzothiazine ring. A wide range of aryl and heteroaryl substituent groups can be installed from commercial boronic acids. Both mono- and diarylated products have been synthesized in good yields and with good functional group tolerance.",10.1055/s-0031-1289741,2012-04-10,0.6096993435537785
Organic Letters,Asymmetric Formal Synthesis of (−)-Cephalotaxine via Palladium-Catalyzed Enantioselective Tsuji Allylation,"Asymmetric synthesis of the pentacyclic alkaloid (-)-cephalotaxine was accomplished via palladium-catalyzed enantioselective Tsuji allylation for construction of the aza-containing tetrasubstituted stereogenic center (95% yield, 93% ee). The allyl enol carbonate precursor was prepared from Hanaoka's ketone intermediate, which was formed by a novel formic acid promoted ring-expansion reaction.",10.1021/acs.orglett.7b04008,2018-02-05,0.6096934644382417
Tetrahedron,Synthesis of intermediates for stereospecific synthesis of α- and β-C-nucleosides: Ring contraction of protected 2-0-trifluoromethanesulphonates of galacto- and altro-pyranosides,,10.1016/s0040-4039(00)96272-5,1987-01-01,0.6096909678136586
Journal of Organic Chemistry,A Photochemical Approach to the Galanthan Ring System,"A five-step, atom-efficient synthesis of the Galanthan tetracyclic skeleton has been developed. The key step is an unusual intramolecular de Mayo reaction using an isocarbostyril substrate with a functionalized tether on nitrogen. The target molecule is produced in 35% overall yield from isocarbostyril.",10.1021/jo0356560,2004-02-06,0.6096788916982366
Tetrahedron,"Practical, efficient, stereoselective, formal synthesis of (2R,3R,4R)-3-hydroxy-4-methylproline",,10.1016/j.tetlet.2003.08.024,2003-09-01,0.6096784895115476
Tetrahedron,A general route to the synthesis of indoloazocines using allyl bromides prepared from Morita–Baylis–Hillman adducts,,10.1016/j.tetlet.2014.12.124,2015-01-05,0.6096764005671499
Organic Letters,Glycomimetic Building Blocks: A Divergent Synthesis of Epimers of Shikimic Acid,A divergent synthesis of (-)-4-epi-shikimic acid was developed. This route features a one-pot zinc-mediated reductive ring opening of an arabinofuranose followed by a Barbier reaction and culminates in a ring-closing metathesis. Functionalization of (-)-4-epi-shikimic acid via conjugate addition of a thiol occurs in high diastereoselectivity to afford a product with the features of fucosylated glycans.,10.1021/ol201252x,2011-06-28,0.6096629395606437
Journal of Organic Chemistry,One-Pot Asymmetric Synthesis of Alkylidene 1-Alkylindan-1-ols Using Brønsted Acid and Palladium Catalysis,"A one-pot catalytic enantioselective allylboration/Mizoroki-Heck reaction of 2-bromoaryl ketones has been developed for the asymmetric synthesis of 3-methyleneindanes bearing a tertiary alcohol center. Brønsted acid-catalyzed allylboration with a chiral BINOL derivative was followed by a palladium-catalyzed Mizoroki-Heck cyclization, resulting in selective formation of the exo-alkene. This novel protocol provides a concise and scalable approach to 1-alkyl-3-methyleneindan-1-ols in high enantiomeric ratios (up to 96:4 er). The potential of these compounds as chiral building blocks was demonstrated with efficient transformation to optically active diol and amino alcohol scaffolds.",10.1021/acs.joc.7b02287,2017-10-07,0.6096592373969713
Organic Process Research & Development,A New Solvent System (Cyclopentyl Methyl Ether–Water) in Process Development of Darifenacin HBr,"Darifenacin is a potent and competitive M 3 selective receptor antagonist (M 3 SRA), and its hydrobromide salt ( 1 ) is the active ingredient of pharmaceutical formulations for oral treatment of urinary incontinence. The present work demonstrates an efficient, commercial manufacturing process for darifenacin hydrobromide ( 1 ).",10.1021/op300119s,2012-09-19,0.6096520991585316
Organic Letters,Total Syntheses of Ningalins D and G,"A flexible synthetic strategy for the total syntheses of ningalins D and G is described. The highly effective TMS-OTf/2,6-lutidine-mediated [3,3]-sigmatropic rearrangement of densely loaded dinaphthyl hydrazides and cyclization of the resulting 2,2'-diamino-1,1'-dinaphthyls afforded the key 7H-dibenzo[c,g]carbazole intermediates. Successful conversions to biphenylene quinone methides followed by regioselective brominations completed the total syntheses of the titled marine alkaloids.",10.1021/acs.orglett.7b02372,2017-08-22,0.6096503506808659
Organic Letters,Asymmetric Synthesis of Both Enantiomers of Arteludovicinolide A,"The first total synthesis of either enantiomer of Arteludovicinolide A and their biological evaluation is reported, featuring a new strategy for the asymmetric construction of γ-butyrolactones with stereogenic side chains in the 4-position. Starting from the renewable resource methyl 2-furoate, the sesquiterpene lactone was synthesized in 9 steps and 4.8% overall yield via an asymmetric cyclopropanation and two diastereoselective nucleophile additions making use of a donor-acceptor-cyclopropane-lactonization cascade. At noncytotoxic concentrations (≤10 μM) (+)-1 was found to have a 15 times higher anti-inflammatory activity (4.87 ± 1.1 μM) than previously reported for concentrations of ≥45 μM.",10.1021/ol401473v,2013-06-24,0.6096441683872827
Angewandte Chemie International Edition,Asymmetric Synthesis of Arboduridine,"The first asymmetric total synthesis of the monoterpenoid indole alkaloid arboduridine has been accomplished. The tricyclic A/B/D ring system was constructed by an enantioselective Michael reaction followed by intramolecular nucleophilic addition. Intramolecular α-amination of a ketone forged the piperidine ring, while a Horner-Wadsworth-Emmons (HWE) reaction was used to form the pyrrolidine ring. A reduction cyclization cascade led to formation of the tetrahydrofuran ring.",10.1002/anie.202316016,2023-12-01,0.6096420510562005
Tetrahedron,New Synthetic Biflavonyls,,10.1016/s0040-4039(01)98936-1,1968-01-01,0.6096358439250124
Tetrahedron,Synthetic new cardenolides,,10.1016/s0040-4039(01)82838-0,1966-01-01,0.6096358439250124
Tetrahedron,"A new synthetic entry into the tricyclo[3.3.0.03,7] octane skeleton",,10.1016/s0040-4039(00)95434-0,1987-01-01,0.6096358439250124
Organic Letters,Studies toward the Tricyclic Core of Phomactin A. Synthesis of the Reduced Furanochroman Subunit,An approach to the tricyclic core of phomactin A is described via the synthesis of a reduced furanochroman model. Key elements of this study include the use of a highly functionalized 1-oxadecalone derivative as a template for the stereoselective introduction of functionality and a tandem retro aldol-epoxide opening-cyclization sequence for elaboration of the dihydrofuran ring.,10.1021/ol0061788,2000-07-21,0.6096280808100369
Tetrahedron,Two-directional synthesis. Part 1: A short formal synthesis of (±)-histrionicotoxin and (±)-histrionicotoxin 235A,,10.1016/s0040-4039(00)01640-3,2000-11-01,0.6096135464711477
Tetrahedron,Synthesis of a Mexican bean beetle azamacrolide allomone via a novel lactam to lactone ring expansion,"The Mixican bean beetle (Epilachna varivestis) defensive secretion azamacrolide 1 has been synthesized via the novel ring expansion of N-hydroxyethyl lactam 12, which was prepared in seven steps from cyclooctanone (6).",10.1016/0040-4039(96)00234-1,1996-03-01,0.6096130182277812
Synlett,"The Facile Synthesis of 2-(Fluorenylmethoxycarbonylamino)-4-(<i>O′</i>,<i>O″</i>-dimethylphosphono)-L-butanoic Acid {Fmoc-Abu(PO<sub>3</sub>Me<sub>2</sub>)-OH}","All articles of this category 2-(Fluorenylmethoxycarbonylamino)-4-(( O′ , O″ -dimethylphosphono)-L-butanoic acid ( 8 ) was prepared in high yield by an improved seven-step procedure which involved sodium borohydride reduction of Boc-Asp-OBu- t 1 , TEMPO-catalysed hypochlorite oxidation of the alcohol 2 and phosphonylation of the aldehyde 3 with dimethyl trimethylsilylphosphite followed by in situ hydrolysis of the silyl group. Homolytic deoxygenation of the 3-hydroxy-4-dimethylphosphonate derivative 4 was effected by its treatment with phenyl chlorothionoformate/4-dimethylaminopyridine followed by treatment of the resultant xanthate 5 with tris(trimethylsilyl)silane/2,2′-azobisisobutyronitrile. The Boc and tert -butyl groups were cleaved from Boc-Abu(PO 3 Me 2 )-OBu- t 6 by acidolytic treatment with trifluoroacetic acid and the Fmoc group was finally introduced using fluorenylmethoxycarbonylsuccinimide to give Fmoc-Abu(PO 3 Me 2 )-OH 8 as a white foam in 50% overall yield.",10.1055/s-1992-22016,1992-01-01,0.6096085187446155
Journal of Organic Chemistry,Domino N<sub>2</sub>-Extrusion–Cyclization of Alkynylarylketone Derivatives for the Synthesis of Indoloquinolines and Carbocycle-Fused Quinolines,"New synthetic approaches for the synthesis of indoloquinolines and carbocycle-fused quinolines have been developed employing alkynylketone substrates. These synthetic transformations involved the application of N 2 -extrusion of azido complexes as a key step to generate carbodiimidium ion and nitrilium ion in situ, which further cyclized intramolecularly with alkyne via a domino process to provide indoloquinolines and carbocycle-fused quinolines, respectively, in moderate to good yields.",10.1021/acs.joc.8b01851,2018-08-07,0.6096057470433116
Angewandte Chemie International Edition,Efficient Route to Tetramethylalumoxane and Carboxylate Alumoxanes through the Alkylation of Phthalic Acid,"Spaced out: The macrocyclic carboxylate-substituted alumoxane 1 and coordination polymer 2 were obtained by stepwise treatment of phthalic acid with AlMe3 and 1,2-bis(4-pyridyl)ethane. In this non-hydrolytic route to alumoxane derivatives, the selective formation of 1 or 2 is determined by the stoichiometric amount of AlMe3 employed.",10.1002/anie.200504414,2006-04-21,0.6095843672007478
Journal of the American Chemical Society,Asymmetric Crotylation Reactions in Synthesis of Polypropionate-Derived Macrolides:  Application to Total Synthesis of Oleandolide,"Complete details of a convergent asymmetric synthesis of oleandolide (1), the aglycon of the macrolide antibiotic oleandomycin, is described. The synthesis has been achieved through the assembly and coupling of the left- and right-hand subunits 12 and 38, respectively. These subunits were prepared from chiral silane-based asymmetric crotylation reactions to control the stereochemical relationships. The left- and right-hand subunits (C1-C7 and C8-C14) were brought together through a Pd(0)-catalyzed sp3-sp2 cross-coupling reaction between the zinc intermediate 40 and vinyl triflate 38 to give 27. This product was converted to seco acid 42a and cyclized to lactone 35 under Yamaguchi conditions. This material was then epoxidized with m-chloroperbenzoic acid (m-CPBA) to install the correct C8 epoxide as a single diastereomer, which after a short deprotection sequence completed the synthesis of oleandolide.",10.1021/ja020853m,2002-10-01,0.6095732660576307
Organic Letters,General Approach for the Synthesis of Sarpagine/Macroline Indole Alkaloids. Enantiospecific Total Synthesis of the Indole Alkaloid Trinervine,[structure: see text] The total synthesis of the indole alkaloid trinervine 1 was accomplished in enantiospecific fashion in an overall yield of 20% (from the tetracyclic ketone 8) in 10 reaction vessels (12.5% from tryptophan methyl ester). The synthesis of the N(a)-H substituted macroline equivalent 2 was also completed in high yield via the same intermediate 13. The unique protection/hydroboration process developed here should provide a method to functionalize the C(19)-C(20) double bond in similar systems.,10.1021/ol0101990,2001-11-16,0.6095623473903622
Tetrahedron,A novel approach to phosphopeptide synthesis-preparation of glu-pser-leu,,10.1016/s0040-4039(01)80081-2,1984-01-01,0.6095596053190279
Tetrahedron,"dl-selective reductive coupling/Dieckmann condensation sequence of α,β-unsaturated amides with samarium(II) iodide/HMPA. Synthesis of a new ligand, trans-1,2-cyclopentanediyl-2,2′-biphenol",,10.1016/0040-4039(96)01951-x,1996-11-01,0.6095540475991726
Synthesis,"A Practical Synthesis of 6,8-Difluoro-7-hydroxycoumarin Derivatives for Fluorescence Applications","A practical synthesis for 6,8-difluoro-7-hydroxycoumarin-3-carboxylic acid – one of the most widely used coumarin fluorescence imaging dye for bioconjugation – is reported. The synthesis was optimized for a preparative scale to obtain 14 g of the fluorescent coumaryl acid, 6,8-difluoro-7-hydroxycoumarin-3-carboxylic acid. Using this sequence, the preparation of its NHS ester requires a single chromatographic separation for a total of eight synthetic steps. Coupling of the key coumaryl NHS ester is also demonstrated with an unprotected hydroxyamine linker chain for further derivatization. This report provides a convenient access to the fluorinated dye for research labs as an alternative to currently cost-prohibitive commercial sources.",10.1055/s-0035-1561603,2016-04-19,0.6095157717405593
Organic Process Research & Development,Development of a Second-Generation Process to Antibacterial Candidate Sulopenem,"The research, development, and scale-up of the broad-spectrum antibacterial candidate sulopenem are presented. An enabled medicinal chemistry synthesis of this active pharmaceutical ingredient was utilized for Phase 1 and early Phase 2 manufacture but was not conducive to larger scale. The limitations associated with the first-generation synthesis were partially addressed in an improved second-generation synthesis of the target molecule where the penem ring is constructed via a modified Eschenmoser sulfide contraction sequence. Other highlights of the second-generation process include an improved synthesis of an important trithiocarbonate intermediate and a superior process for Pd-catalyzed deallylation of the penultimate ester to obtain low levels of residual palladium.",10.1021/op300130p,2012-07-13,0.6095150939960878
Tetrahedron,Vilsmeier-haack reactoin of glycals-a short route to C-2-formyl glycals,,10.1016/s0040-4039(00)79402-0,1991-07-01,0.6095124722826399
Tetrahedron,A short and divergent route to 2-alkenyl-4-quinolones,,10.1016/j.tetlet.2018.08.062,2018-08-30,0.6095124722826399
Journal of the American Chemical Society,Total Synthesis of (±)-Perophoramidine,The first total synthesis of racemic perophoramidine is described. The key step features the highly stereoselective introduction of the vicinial quaternary centers via base-promoted carbon-carbon bond formation between a 3-alkylindole and a 3-bromo-3-alkylindolin-2-one. This transformation presumably proceeds through a conjugate addition or Diels-Alder cycloaddition of the 3-alkylindole with a 3-alkylindol-2-one intermediate.,10.1021/ja049569g,2004-04-02,0.6095113164391048
European Journal of Organic Chemistry,Multigram Synthesis of Heterabicyclo[n.1.0]alkan‐1‐yl Trifluoroborates,"An approach to the synthesis of oxa‐ and azabicyclo[ n .1.0]alkan‐1‐yl trifluoroborates on a multigram scale was developed. Two synthetic strategies were evaluated: the first based on the lithiation–borylation of the corresponding 2‐bromoallyl derivatives, and the other relying on regioselective hydroboration of the appropriate hetera‐substituted enynes. The second method appeared to be more efficient in terms of scalability and substrate scope. Further steps included ring closing‐metathesis, mild palladium‐catalyzed cyclopropanation with diazomethane, and reaction with KHF 2 and furnished the title compounds in up to 50 g scale in a single run (10–41 % overall yield, 4–5 steps).",10.1002/ejoc.202000977,2020-09-10,0.6095076724494637
Angewandte Chemie International Edition,Enantioselective Total Synthesis of the Marine Toxin (−)‐Gymnodimine Employing a Barbier‐Type Macrocyclization,"Sea the synthesis: At ambient temperature, tert-butyllithium promotes a Barbier-type macrocyclization in the first total synthesis of (−)-gymnodimine (Ts: toluene-4-sulfonyl; TBS: tert-butyldimethylsilyl), a member of the spirocyclic-imine family of marine toxins. The synthesis also features a vinylogous Mukaiyama aldol process to couple the labile butenolide moiety onto a macrocyclic ketone intermediate.",10.1002/anie.200903432,2009-09-02,0.6095070708495854
Angewandte Chemie International Edition,Concise Photochemical Synthesis of the Antimalarial Indole Alkaloid Decursivine,"A four-step synthesis of the extracyclic, antimalarial indole natural product decursivine is described starting from commercial piperonyl bromide and serotonin (see scheme). A photoinitiated reaction cascade involving indole radical cation formation, rearrangement, radical recombination, rearomatization, elimination, and diastereoselective auto-acid-catalyzed closure of the dihydrofuran ring combine in a single step to conclude this remarkably efficient synthesis.",10.1002/anie.201006423,2011-04-07,0.6095042361009942
Organic Letters,An Organoiron Approach to the Benzophenone Appendage of the Protein Kinase C Inhibitor Balanol,"[formula: see text] A new synthetic route to the benzophenone appendage of balanol, based on sequential iron-assisted nucleophilic aromatic substitution and ring-opening as well as regioselective oxidative cyanation, is described.",10.1021/ol9910060,1999-10-07,0.6094992443972271
European Journal of Organic Chemistry,Development of an Efficient Synthesis of <i>rac</i>‐3‐Demethoxyerythratidinone via a Titanium(III) Catalyzed Imine‐Nitrile Coupling,"We herein describe the evolution of a rapid, high‐yielding synthesis of the erythrina alkaloid 3‐demethoxyerythratidinone. The natural product is assembled in six steps from commercial precursors in 30–35 % overall yield and with only two chromatographical purification operations. The key step is a titanium(III) catalyzed umpolung reaction in form of a reductive imine–nitrile coupling that can be combined with a subsequent cyclization reaction on a 50 mmol scale. Furthermore, optimized Wacker oxidation conditions enable the selective alkene oxidation in the presence of a tertiary amine functionality, which has been a problem in previous syntheses of erythrina alkaloids. The racemic route can be used to prepare the natural product on gram scale and the results may be useful for the synthesis of related alkaloids.",10.1002/ejoc.201801479,2018-11-07,0.6094866107776142
Synlett,"A New Entry to Polyfunctionalized4,5-<i>trans</i>Disubstituted Oxazolidin-2-ones from<scp>l</scp>-Aspartic Acid","A straightforward synthesis of enantiomerically pure (4R,5S)-5-oxazolidinecarboxylic acid, 2-oxo-4-[(t-butyldimethyl-silyloxy)methyl]-, benzyl ester and of (4S,5S)-4-oxazolidinecarboxylic acid, 2-oxo-5-[(t-butyldimethylsilyloxy)methyl]-, benzyl ester was envisaged starting from readily available L-aspartic acid. The key step is the diastereoselective addition of iodine with the introduction of a new stereogenic centre.",10.1055/s-2003-38733,2003-01-01,0.6094854633022321
Tetrahedron,An efficient route for commercially viable syntheses of furan- and thiophene-anellated β-hydroxychalcones,,10.1016/j.tetlet.2005.06.111,2005-07-12,0.6094776996017333
Synlett,A Robust Route towards Functionalized Pyrrolizidines as Precursors for Daphniphyllum Alkaloids,"A diastereoselective Fráter–Seebach-type alkylation provides access to a highly functionalized pyrrolizidine, which could serve as a key building block for the total synthesis of ­Daphniphyllum alkaloids, such as oldhamine A.",10.1055/s-0033-1340677,2014-02-13,0.609475379415648
Journal of Organic Chemistry,Synthesis of Chiral Nitroxides and an Unusual Racemization Reaction,"Lai's protocol for the synthesis of nitroxides has been extended to the synthesis of several new chiral piperazine and morpholine nitroxides. This strategy utilizes the Bargellini reaction as the key bond-forming step. Several optically pure nitroxides incorporating alpha-aromatic and alpha-spiro centers were prepared by this route. These chiral nitroxides will be of interest as enantioselective oxidants, as traps for prochiral radicals, and in the preparation of new materials. One of these nitroxides, compound 43, was found to racemize under mild oxidizing conditions. The mechanism for this unusual racemization reaction was investigated.",10.1021/jo9808831,1998-08-20,0.6094661322179098
Synthesis,"Microwave-Assisted Synthesis of KN-93, a Potent and Selective Inhibitor of Ca²+/Calmoduline-Dependent Protein Kinase II","Convenient synthetic routes to KN-93, N-(2-{[[(2E)-3-(4-chlorophenyl)prop-2-enyl](methyl)amino]methyl}phenyl)-N-(2-hydroxyethyl)-4-methoxybenzenesulfonamide, a well-known Ca(2+)/calmoduline-dependent protein kinase II (CaMKII) inhibitor, are described. The methods proposed start from easily available reagents and allow ready preparation of the final compound in moderate overall yields. Most of the synthetic steps proposed were microwave assisted.",10.1055/s-0030-1258298,2010-10-14,0.6094655876572239
Tetrahedron,A stereoselective synthesis of 2-acetamido-2-deoxy-C-glucosides: Glycosyl dianions as key intermediates,,10.1016/0040-4039(94)88077-8,1994-08-01,0.6094456124328909
Tetrahedron,A new dimeric imidazole alkaloid plasmid conjugation inhibitor from Lepidium sativum,,10.1016/j.tetlet.2018.04.028,2018-04-11,0.6094265821693036
Synlett,Total Synthesis of <i>ent</i>-Sedridine Using Proline-Catalyzed Asymmetric Addition as a Key Step,A total synthesis of ent-sedridine is described. The development of a new method for the construction of the C-2 chiral center of the piperidine ring was achieved using a proline-catalyzed Mannich reaction. Reaction of 4-hydroxybutanal and p-anisidine to form an imine and subsequent addition of acetone gave the key chiral aliphatic precursor with high enantioselectivity.,10.1055/s-2006-948203,2006-09-01,0.6094239699898129
Journal of Organic Chemistry,"2,3-Bis(phenylsulfonyl)-1,3-butadiene as a Reagent for the Synthesis of the Azatricyclic Core of (±)-Halichlorine","An efficient stereocontrolled route to the azatricyclic core of an advanced halichlorine intermediate is described. Reaction of the oxime derived from 2-(oxo-cyclopentyl)acetic acid ethyl ester with 2,3-bis(phenylsulfonyl)-1,3-butadiene gives rise to a 7-oxa-1-azanorbornane cycloadduct in high yield. The formation of the bicyclic isoxazolidine arises from conjugate addition of the oxime onto the diene to afford a transient nitrone that then undergoes an intramolecular dipolar cycloaddition. Treatment of the cycloadduct with 5% Na/Hg results in reductive nitrogen-oxygen bond cleavage to furnish a spirocyclic piperidinone, which was further elaborated to an advanced intermediate employed in an earlier synthesis of halichlorine.",10.1021/jo100055u,2010-02-12,0.6094176830807352
Tetrahedron,Development of novel C2-symmetrical [5]oxahelicenoid diols,,10.1016/j.tetlet.2021.153026,2021-03-26,0.6094165126983789
Journal of Organic Chemistry,Convergent Synthesis of the C1–C29 Framework of Amphidinolide F,"The complete carbon framework of the macrocyclic marine natural product amphidinolide F has been prepared by a convergent synthetic route in which three fragments of similar size and complexity have been coupled. Key features of the syntheses of the fragments include the stereoselective construction of the tetrahydrofuran in the C1-C9 fragment by oxonium ylide (free or metal-bound) formation and rearrangement triggered by the direct generation of a rhodium carbenoid from 1-sulfonyl-1,2,3-triazole, the highly diastereoselective aldol reaction between a boron enolate and an aldehyde with 1,4-control to prepare the C10-C17 fragment, and the formation of the tetrahydrofuran in the C18-C29 fragment by intramolecular nucleophilic ring opening of an epoxide with a hydroxyl group under acidic conditions.",10.1021/acs.joc.2c00850,2022-06-08,0.6094130151294421
Tetrahedron,Ugi multicomponent reaction with hydroxylamines: an efficient route to hydroxamic acid derivatives,,10.1016/j.tetlet.2004.06.068,2004-07-07,0.6094099263559177
Journal of Organic Chemistry,"Synthesis of 1-Amino-3-[2-(1,7-dicarba-<i>closo-</i>dodecaboran(12)-1-yl)ethyl]cyclobutanecarboxylic Acid:  A Potential BNCT Agent","The synthesis of an unnatural amino acid, 1-amino-3-[2-(1,7-dicarba-closo-dodecaboran(12)-1-yl)ethyl]cyclobutanecarboxylic acid, was achieved. This new potential BNCT agent was prepared via the monoalkylation of m-carborane with 4-bromobutene to produce 4-m-carboranyl-1-butene, which was then subjected to a 2 + 2 cycloaddition using dichloroketene. The resultant boronated cyclobutanone was reductively dechlorinated prior to the formation of the corresponding hydantoin, which was hydrolized to the title compound in excellent yield.",10.1021/jo970148+,1997-06-01,0.6094056327680797
Organic Letters,"Enantioselective Total Synthesis of (−)-Zampanolide, a Potent Microtubule-Stabilizing Agent",An enantioselective total synthesis of zampanolide has been accomplished using a novel DDQ/Brønsted acid promoted cyclization as the key reaction. The synthesis features cross-metathesis to construct the trisubstituted olefin and a ring-closing metathesis to form the macrolactone. The final N-acyl aminal formation was stereoselectively accomplished by an organocatalytic reaction.,10.1021/ol201626h,2011-07-12,0.6093999223939396
Organic Letters,Synthesis of Jenamidines A<sub>1</sub>/A<sub>2</sub>,"[reaction: see text] Addition of the enolate of tert-butyl acetate to cyanamide methyl ester 17 followed by treatment with LHMDS afforded vinylogous urea 19 in 27% yield. Vinylogous urea 19 was also obtained from 37 and tert-butyl cyanoacetate in 50% yield. Acylation of 19 with acid chloride 31d, followed by hydrolysis of the tert-butyl ester and decarboxylation with 9:1 CH2Cl2/TFA and very mild basic hydrolysis of the methoxyacetate ester, afforded jenamidines A1/A2 (3) in 45% yield. This first synthesis confirms our reassignment of the jenamidines A1/A2 structure.",10.1021/ol0518784,2005-08-27,0.6093945231837378
Tetrahedron,A novel asymmetric synthesis of α-aminoacids from nitriles employing diisopinocampheylborane as a chiral agent,,10.1016/s0040-4039(01)93987-5,1972-01-01,0.6093908042594331
Tetrahedron,"Selective reduction of aromatic azides with hexamethyldisilathiane: synthesis of new 2-azidopyrrolo[2,1-c][1,4]benzodiazepines",,10.1016/j.tetlet.2004.02.148,2004-03-25,0.6093757212906726
Organic Letters,Concise Enantioselective Total Synthesis of Neopeltolide Macrolactone Highlighted by Ether Transfer,"A concise total synthesis of neopeltolide macrolactone has been accomplished in 14 steps in the longest linear sequence, 15 steps overall from commercially available materials. The present synthesis was highlighted by successful exploitation of ether transfer methodology and a radical cyclization reaction to directly establish the requisite stereochemistry of the tetrahydropyran core.",10.1021/ol802254z,2008-10-15,0.6093670345837171
Tetrahedron,"Synthesis of novel 3-substituted-2,3-dihydro-1,4-dioxino[2,3-b]pyridines as potential new scaffolds for drug discovery: selective introduction of substituents on the pyridine ring",,10.1016/j.tetlet.2003.10.005,2003-11-14,0.6093664707541551
Journal of Organic Chemistry,Stereoselective Synthesis of Neu5Acα(2→5)Neu5Gc:  The Building Block of Oligo/Poly(→5-<i>O</i><sub>g</sub><sub>lycolyl</sub>Neu5Gcα2→) Chains in Sea Urchin Egg Cell Surface Glycoprotein,"The synthesis of a sialic acid dimer derivative, Neu5Acalpha(2-->5)Neu5Gc, is described. The synthetic strategy is based on the use of allyl alcohol to achieve an exclusive alpha-sialylation product. The allyloxy group is also a latent glycolic acid that provides the subsequent coupling with neuraminate with minimal protection-deprotection manipulations.",10.1021/jo025988p,2002-09-18,0.6093640148153954
Angewandte Chemie International Edition,Enantioselective Total Synthesis of (+)‐Garsubellin A,"Garsubellin A is a meroterpene capable of enhancing the enzyme choline acetyltransferase whose decreased level is believed to play a central role in the symptoms of Alzheimer's disease. Due to the potentially useful biological activity together with the novel bridged and fused cyclic molecular architecture, garsubellin A has garnered substantial synthetic interest, but its absolute stereostructure has been undetermined. We report here the first enantioselective total synthesis of (+)-garsubellin A. Our synthesis relies on stereoselective fashioning of a cyclohexanone framework and double conjugate addition of 1,2-ethanedithiol that promotes aldol cyclization to build the bicyclic [3.3.1] skeleton. The twelve-step, protecting group-free synthetic route has enabled the syntheses of both the natural (-)-garsubellin A and its unnatural (+)-antipode for biological evaluations.",10.1002/anie.202109193,2021-08-16,0.6093636525770791
Journal of the American Chemical Society,"Allyl Alcohol as an Acrolein Equivalent in Enantioselective C–C Coupling: Total Synthesis of Amphidinolides R, J, and S","The first systematic study of catalytic enantioselective 1,2-additions to acrolein is described. Specifically, using allyl alcohol as a tractable, inexpensive acrolein proelectrophile, iridium-catalyzed acrolein allylation is achieved with high levels of regio-, anti -diastereo-, and enantioselectivity. This process delivers 3-hydroxy-1,5-hexadienes, a useful compound class that is otherwise challenging to access via enantioselective catalysis. Two-fold use of this method unlocks concise total syntheses of amphidinolide R (9 vs 23 steps, LLS) and amphidinolide J (9 vs 23 or 26 steps, LLS), which are prepared in fewer than half the steps previously possible, and the first total synthesis of amphidinolide S (10 steps, LLS).",10.1021/jacs.3c01809,2023-03-30,0.6093633020593452
Tetrahedron,An efficient synthesis of tetrasubstituted imidazoles from N-(2-Oxo)-amides,,10.1016/s0040-4039(98)02058-9,1998-12-01,0.6093596909846328
Tetrahedron,"Formation of methyl homodaphniphyllate, a plausible intermediate between daphniphylline and yuzurimine, and isolation of two new alkaloids",,10.1016/s0040-4039(01)88022-9,1969-01-01,0.6093586138244169
Journal of Organic Chemistry,"Asymmetric synthesis. 29. Preparation of 1,8-diazaspiro[5.5]undecane derivatives","From 2-cyano-6-phenyloxazolopiperidine, two highly efficient routes have been developed for the asym. synthesis of the spiropiperidine system: 1,8-diazaspiro[5.5]undecane. The key step was generation of the imine salts from the functionalized alpha -amino nitrile I, by nucleophilic addn. of a suitable organometallic reagent to the nitrile group followed by, in situ, intramol. nucleophilic alkylation. A reductive-cyclization procedure allowed the prepn. of nonsubstituted and monosubstituted spiro compds. II (R = H, pentyl), while an alkylation-cyclization procedure led to the disubstituted spiro deriv. III, an aza analog of perphydrohistrionicotoxin. [on SciFinder (R)]",10.1021/jo00075a048,1993-11-01,0.6093506896377905
Organic Letters,Domino Reactions for the Synthesis of Anthrapyran-2-ones and the Total Synthesis of the Natural Product (±)-BE-26554A,"A domino alkyne addition/CO insertion/Nu acylation reaction to a series of novel anthrapyran-2-ones in good to excellent yields is described. In addition, an efficient synthetic sequence involving carbonylation, formation of a β-keto-sulfoxide, and cyclization is presented en route to the antibiotic and antitumor compound (±)-BE-26554A.",10.1021/ol402240v,2013-09-05,0.6093458712078919
Organic Process Research & Development,A Fit-for-Purpose Synthesis of (<i>R</i>)-2-Methylazepane,"The preparation of new RSV inhibitors required an efficient synthesis of ( R )-2-methylazepane (( R )- 1 ) amenable to large-scale production to support preclinical studies. After consideration of different options, an efficient five-step synthesis relying on the preparation of the racemic N -Boc precursor and its purification by chiral SFC was developed and successfully implemented on a 400 g scale.",10.1021/acs.oprd.9b00425,2019-12-12,0.6093436211599157
Journal of the American Chemical Society,Enantioselective Total Synthesis of (−)-Cyathin B<sub>2</sub>: A Desymmetric Double-Allylboration Approach,"A powerful Pt-catalyzed asymmetric diboration/desymmetric double-allylboration cascade reaction has been developed for the construction of synthetically useful, densely functionalized hydrindanes with five stereocenters, including three quaternary ones, in good yields and excellent enantiomeric excess (ee) values within a single synthetic operation. A unified strategy utilizing this key tandem methodology enabled the concise asymmetric total synthesis of cyathane diterpene (−)-Cyathin B 2 in 14 steps from commercially available starting materials, thereby demonstrating its remarkable potential in the synthesis of hydrindane-containing natural products and pharmaceuticals.",10.1021/jacs.4c08042,2024-08-28,0.6093423170153329
Synlett,"A Novel Total Synthesis of Indolo[2,3-<i>b</i>]naphthalene-6,11-diones","A new total synthesis of indolo[2,3-b]naphthalene-6,11-diones is described, which involves a novel opening of 2-(2′-nitrophenyl)-2-methoxycarbonyl-1-indanones to 2-[2-methoxycarbonyl-2-(2-nitrophenyl)ethyl]benzoic acids followed by a two-steps transformation of the latter into 2-(1H-indol-3-ylmethyl)benzoic acid methyl esters, which are then converted into the target compounds in three steps.",10.1055/s-2004-815397,2004-01-01,0.6093405120553658
Journal of Organic Chemistry,Ortho- and Para-Substituted Hoveyda−Grubbs Carbenes. An Improved Synthesis of Highly Efficient Metathesis Initiators,"A novel highly efficient and general route to various 3- and 5-substituted 2-alkoxystyrenes, required for the preparation of Hoveyda-Grubbs catalysts, is described.",10.1021/jo049222w,2004-08-27,0.6093383635462508
Angewandte Chemie International Edition,Total Synthesis of the Unusual Monoterpenoid Indole Alkaloid (±)‐Alstilobanine A,"Tetracyclic monoterpene alkaloid alstilobanine A was obtained in racemic form. The pivotal steps of the total synthesis are a novel conjugate addition of an ester enolate with a nitrosoalkene, as well as a formal [2+2] intramolecular cycloaddition leading to a β-lactone to generate the requisite cis-fused 2-azadecalin moiety of the alkaloid. TMSE=trimethylsilylethoxy, Ts=4-toluenesulfonyl.",10.1002/anie.201207949,2012-11-19,0.609329759720301
Tetrahedron,"A diastereospecific, non-racemic synthesis of a novel β-hydroxy-δ-lactone HMG-CoA reductase inhibitor",,10.1016/s0040-4039(00)98589-7,1985-01-01,0.6093214218659293
Organic Letters,Enantioselective Synthesis of Pyrrolopyrimidine Scaffolds through Cation-Directed Nucleophilic Aromatic Substitution,"The catalytic enantioselective synthesis of 3-aryl-substituted pyrrolopyrimidines (PPYs), a common motif in drug discovery, is achieved through a kinetic resolution via quaternary ammonium salt-catalyzed nucleophilic aromatic substitution (S N Ar). Both enantioenriched products and starting materials can be functionalized with no observed racemization to give enantiodivergent access to diverse chiral analogues of an important class of kinase inhibitor. One of the compounds was found to be a potent and selective inhibitor of breast tumor kinase.",10.1021/acs.orglett.8b00579,2018-03-21,0.6093148687655084
Journal of Organic Chemistry,"A One-Pot Route to Indole-3-acetaldehydes, Tryptophols, and Tryptamine-Based Alkaloids from Indoles","An efficient and operationally simple Brønsted acid catalysis provides a direct scalable route to indole-3-acetaldehydes starting from readily available indole derivatives. A number of tryptophols and tryptamines were accessed from these valuable precursors through simple functional group interconversions. Further showcasing the utility of this strategy, syntheses of tryptamine-based marine alkaloids deformylflustrabromine and brocaeloid C, and a selective h5-HT 2A receptor antagonist, were accomplished in one-pot operation. To note, the latter antagonist was obtained in gram-scale, demonstrating the scalability of this one-pot sequential protocol.",10.1021/acs.joc.5c02386,2025-10-27,0.6093055822610357
Synlett,Superacid Catalyzed Hydroxyalkylation of Aromatics with Ethyl Trifluoropyruvate: A New Synthetic Route to Mosher’s Acid Analogs,A new superacid catalyzed Friedel-Crafts hydroxy­alkylation of aromatics with ethyl trifluoropyruvate is described. The trifluoromethanesulfonic acid or gallium(III) trifluoromethanesulfonate catalyzed reactions give α-hydroxy α-trifluoromethyl phenyl acetic acid ethyl ester and its derivatives (analogs of Mosher’s acid) in good yields for both highly activated hetero­aromatics and substituted benzenes.,10.1055/s-2003-37517,2003-01-01,0.6093055324853405
Organic Letters,Synthesis of the C22−C26 Tetrahydropyran Segment of Phorboxazole by a Stereoselective Prins Cyclization,"[formula: see text] Tetrahydropyran rings are found in many complex natural products, and the segment-coupling Prins cyclization is an effective strategy for their synthesis. We report a four-step, stereoselective synthesis of the C20-C27 tetrahydropyran segment of phorboxazole. The key step is a Prins cyclization induced by catalytic BF3.OEt2.",10.1021/ol005646a,2000-04-12,0.6092951219372205
Tetrahedron,A facile construction of the tricyclic 5-7-6 scaffold of fungi-derived diterpenoids. The first total synthesis of (±)-heptemerone G and a new approach to Danishefsky’s intermediate for a guanacastepene A synthesis,,10.1016/j.tetlet.2010.06.064,2010-06-18,0.6092919058271251
Journal of Organic Chemistry,Total Synthesis of Natural Dysidiolide,"Dysidiolide (1), a novel sesterterpenoid previously isolated from the Caribbean sponge Dysidea etheria de Laubenfels, inhibits the action of the protein phosphatase, cdc25A. The authors establish a novel total synthesis of natural dysidiolide (1) using intramolecular Diels-Alder reaction as the key step from optically active cyclohexenone 3. Decalin, the core structure of 1, was constructed by intramolecular Diels-Alder reaction of the diene ester generated by elimination of the phenyl sulfoxide group from sulfoxide ester 6 prepared from cyclohexenone 3. Diastereoselective methylation at C-7, alkylation at C-6, and deoxygenation of C-12 and C-24 positions gave the fully substituted bicyclic core of 1. The two side chains of the bicyclic core were further extended so as to afford natural dysidiolide (1). The total yield of this synthesis exceeds that of previous syntheses of 1.",10.1021/jo0015772,2001-01-27,0.609289096669468
Tetrahedron,Diastereoselective addition of organolithiums to new chiral hydrazones. Enantioselective synthesis of (R)-coniine,,10.1016/0040-4039(96)01151-3,1996-07-01,0.6092825567344191
Synlett,Preparation of the Geranyl-α-pyrone (±)-Aurantiacone via a New Pyrone Synthesis,"The structure of the leaf resin geranyl-α-pyrone aurantiacone isolated from Mimulus ( = Diplacus) aurantiacus (Curtis) Jeps. (Scrophulariaceae) was confirmed through synthesis. The key step is lactonization of the sensitive 5-hydroxy-3-oxopent-4-enoic acid under mild conditions, which can be released from the corresponding bispotassium salt. The latter is accessible in a few steps from an N-acyl aziridine and an ethyl acetoacetate.",10.1055/s-2007-967996,2007-02-01,0.6092748322661432
Tetrahedron,Synthesis of C3-epi-virenose and anomerically activated derivatives,"A 9-step synthetic route to a protected form of the C3-epimer of virenose from d-fucose is described. C3-epi-virenose is the carbohydrate unit of the bioactive polyketide elsamicin B and part of the carbohydrate unit of elsamicin A. The developed route enabled preparation of anomerically activated forms of this unique C6-deoxy sugar, including derivatives with 1-acetyl, 1-acetylthio, 1-trichloroacetimidate, 1-bromo, and 1-fluoro substituents.",10.1016/j.tetlet.2024.155041,2024-03-28,0.6092732700086972
Tetrahedron,"A palladium-catalyzed route to mono- and diprotected -2-cyclopentene-1,4-diols",,10.1016/s0040-4039(01)80901-1,1985-01-01,0.6092588818846967
Synthesis,Stereoselective Total Synthesis of (-)-β-Conhydrine and (+)-α-Conhydrine,"We have carried out the stereoselective synthesis of (-)-β-conhydrine and (+)-α-conhydrine, two bioactive α-hydroxyalkyl-substituted piperidines, using the commercially available and inexpensive amino alcohol (S,S)-(+)-pseudoephedrine as chiral auxiliary. The key step of this synthesis relies on new methodology previously developed in our group, consisting of the chemo- and dia­stereoselective addition of Grignard reagents across the C=N bond of α-iminoglyoxylamides derived from (S,S)-(+)-pseudoephedrine followed by the selective monoaddition of organolithium reagents­ to the carbamoyl group, leading to the formation of enantioenriched α-amino ketones.",10.1055/s-0030-1258390,2011-01-05,0.6092556433485867
European Journal of Organic Chemistry,"A Novel Rearrangement of Cyclic Glutamine Derivatives: Ring Contraction in 3,6‐Diamino‐2,3,4,5‐tetrahydropyridin‐2‐ones to Yield 5‐Iminoproline Amides","Abstract A new rearrangement of the cyclic L ‐glutamine derivative( S )‐6‐carbamoylamino‐3‐(methylamino)‐2,3,4,5‐tetrahydropyridin‐2‐one ( 2 ) and its descarbamoyl analogue 10 ‐H was found to yield enantiomerically pure 5‐carbamoylimino‐1‐methyl‐ L ‐proline amide ( 12 ‐CONH 2 ) and its descarbamoyl analogue 12 ‐H, respectively. Cyclic amidines 2 and 10 ‐H were generated from the amide N 2 ‐ZGlnOEt 3 in seven and six steps, respectively. Deprotection of ( S )‐6‐amino‐3‐[( N ‐benzyloxycarbonyl‐ N ‐methyl)amino]‐2,3,4,5‐tetrahydropyridin‐2‐one ( 8 ) led directly to 5‐iminoproline amide 12 ‐H (via 10 ‐H and the bicyclic orthoamidine 11 ‐H) in 66 % overall yield from 3 . Carbamoylation of 8 with ZNCO (Z = PhCH 2 OCO) followed by hydrolytic removal of both Z groups gave 5‐(carbamoylimino)proline amide 12 ‐CONH 2 (via 2 and orthoamidine 11 ‐CONH 2 ) in 70 % overall yield from 3 .",10.1002/ejoc.201100404,2011-06-08,0.60924727659581
Organic Process Research & Development,The Fit For Purpose Development of S1P<sub>1</sub> Receptor Agonist GSK2263167 Using a Robinson Annulation and Saegusa Oxidation to Access an Advanced Phenol Intermediate,"A fit for purpose approach has been adopted in order to develop a robust, scalable route to the S1P 1 receptor agonist, GSK2263167. The key steps include a Robinson ring annulation followed by a Saegusa oxidation, providing rapid access to an advanced phenol intermediate. Despite the use of stoichiometric palladium acetate for the Saegusa oxidation, near complete recovery of the palladium has been demonstrated. The remaining steps have been optimised including the removal of all chromatography. An alternative to the Saegusa oxidation is described as well as the development of a flow process to facilitate further scale-up of the amidoxime preparation using hydroxylamine at elevated temperature.",10.1021/op400162p,2013-09-05,0.6092383603019736
Organic Letters,"Catalytic Asymmetric Total Synthesis of Hedyosumins A, B, and C","The first and asymmetric total synthesis of hedyosumins A, B, and C was accomplished in 13-14 steps from simple starting materials. The essential tools that allow us to access the tetracyclic skeleton include an organocatalytic [4 + 3] cycloaddition reaction, an intramolecular aldol condensation, and an intramolecular carboxymercuration/demercuration enabled lactonization. A CBS-catalyzed asymmetric reduction was employed to boost the ee of the synthetic natural products to an excellent level. This synthesis established the absolute configurations of hedyosumins A, B, and C.",10.1021/acs.orglett.6b00150,2016-02-29,0.6092334926545451
Tetrahedron,An improved and practical procedure for the synthesis of substituted phenylacetylpyridines,,10.1016/s0040-4039(98)00140-3,1998-03-01,0.6092329205210292
Synlett,Efficient Synthesis of Gemcitabine 5′-O-Triphosphate Using Gemcitabine 5′-O-Phosphoramidate as an Intermediate,"A new efficient approach for the synthesis of gemcitabine triphosphate has been developed. The method is based on the ring-opening reaction of 2-cyanoethoxy-2-oxo-1,3,2-oxathia­phospholane with protected gemcitabine in the presence of DBU. Subsequent treatment of gemcitabine monophosphate with DCC in the presence of ammonia provides gemcitabine 5′- O -phosphoramidate. Finally, this compound, on reaction with pyrophosphate, furnishes gemcitabine 5′-triphosphate in 50% yield.",10.1055/s-0034-1378353,2014-07-09,0.6092286210876482
Angewandte Chemie International Edition,Synthetic Study Towards Azadirachtin: An Efficient and Stereoselective Construction of the AB Rings with Full Functionality,"From A to B: The decalin moiety of azadirachtin, which includes the fully functionalized AB ring system (see picture), was synthesized stereoselectively in only 23 steps. Key steps include an intramolecular Diels–Alder reaction, a decarboxylation, a Claisen rearrangement, and finally a tandem radical cyclization.",10.1002/anie.200604097,2007-01-17,0.6092264207905763
Organic Letters,"Asymmetric Synthesis of the Tetrahydropyran Ring, C32−C38 Fragment, of Phorboxazoles","The asymmetric synthesis of a model aldehyde (2R,6R)-2 and the C32-C38 fragment of phorboxazoles, (2R,4R,6R)-1, is described using a sulfoxide as chiral auxiliary. Key advances include the stereoselective reductions of beta-keto- or beta,gamma-diketosulfoxides, the acid-catalyzed cyclization of enantiopure sulfinyl hydroxy ketone precursors to the tetrahydropyran ring, and the Pummerer reaction on the pendant sulfoxide to create the formyl group.",10.1021/ol048099s,2004-10-08,0.6092250929127992
Synthesis,"A Simple Route to Benzo[b]xanthene-6,11,12-triones: Synthesis of Bikaverin","A three-step procedure for the synthesis of 1H-benzo[b]xanthene-6,11,12-trione derivatives is described. The procedure involves the halogenation of 12-(3-hydroxy-1,4-naphthoquinon-2-yl)-6H-benzo[b]xanthene-6,11-(12H)-diones, followed by treatment with water under aeration. In this manner, bikaverin, a cytotoxic metabolite isolated from several species of the fungal genera Gibberella, Fusarium, and Mycogone, was synthesised.",10.1055/s-0036-1591587,2018-07-09,0.6092242072595796
Tetrahedron,C2-symmetrical sterol–polyether conjugates as highly efficient synthetic ionophores,,10.1016/s0040-4039(03)01454-0,2003-07-16,0.6092188041862678
European Journal of Organic Chemistry,Chemoenzymatic Asymmetric Synthesis of Serotonin Receptor Agonist (<i>R</i>)‐Frovatriptan,"Abstract A simple chemoenzymatic asymmetric route has been developed for the production of antimigraine agent ( R )‐Frovatriptan. Lipases and oxidoreductases have been identified as ideal biocatalysts for the production of enantiopure adequate synthetic intermediates under safe and environmentally friendly conditions. ( S )‐3‐Hydroxy‐2,3,4,9‐tetrahydro‐1 H ‐carbazole‐6‐carbonitrile, an optimal building block for the synthesis of the drug, has been efficiently prepared through Candida antarctica lipase type B catalyzed acylation of its corresponding racemic mixture or alcohol dehydrogenase A mediated bioreduction of the corresponding ketone. The inversion of the chiral center has been identified as a key step, optimizing the process to avoid partial racemization. Finally, amine functionalization and nitrile hydrolysis have allowed the production of ( R )‐Frovatriptan in enantiomerically pure form.",10.1002/ejoc.201300114,2013-05-07,0.609200611963774
Tetrahedron,"Asymmetric synthesis of (R)-(+)-6-(1,4-dimethoxy-3-methyl-2-naphthyl)-6-(4-hydroxyphenyl)hexanoic acid as a key intermediate for a neurodegenerative disease agent",,10.1016/j.tetlet.2004.08.045,2004-09-14,0.6091892120667599
European Journal of Organic Chemistry,"High‐Yielding Diastereoselective <i>syn</i>‐Dihydroxylation of Protected HBO: An Access to D‐(+)‐Ribono‐1,4‐lactone and 5‐<i>O</i>‐Protected Analogues","A diastereoselective chemoenzymatic synthetic pathway to D‐(+)‐ribono‐1,4‐lactone, a versatile chiral sugar derivative widely used for the synthesis of various natural products, has been designed from cellulose‐based levoglucosenone ( LGO ). This route involves a sustainable Baeyer‐Villiger oxidation of LGO to produce enantiopure (S)‐γ‐hydroxymethyl‐α,β‐butenolide ( HBO ) that is further functionalized with various protecting groups to provide 5‐ O ‐protected γ‐hydroxymethyl‐α,β‐butenolides. The latter then undergo a diastereoselective and high‐yielding syn ‐dihydroxylation of the α,β‐unsaturated lactone moiety followed by a deprotection step to give D‐(+)‐ribono‐1,4‐lactone. Through this 4‐step synthetic route from LGO , D‐(+)‐ribono‐1,4‐lactone is obtained with d.r. varying from 82:18 to 97:3 and in overall yields between 32 and 41 % depending on the protecting group used. Moreover, valuable synthetic intermediates 5‐ O ‐ tert ‐butyldimethylsilyl‐, 5‐ O ‐ tert ‐butyldiphenylsilyl‐ as well as 5‐ O ‐benzyl‐ribono‐1,4‐lactones are obtained in 3 steps from LGO in 58, 61 and 40 %, respectively.",10.1002/ejoc.201801780,2018-12-05,0.6091795719762748
Journal of Organic Chemistry,A Direct Asymmetric Synthesis of Juglomycin A,Juglomycin A has been synthesized in four steps from 5-methoxy-1-naphthol.,10.1021/jo952077p,1996-01-01,0.6091792267944452
Journal of Organic Chemistry,"Divergent Diastereoselective Synthesis of Iridomyrmecin, Isoiridomyrmecin, Teucrimulactone, and Dolicholactone from Citronellol","The iridoid natural products iridomyrmecin, isoiridomyrmecin, teucriumlactone, and dolicholactone were prepared from citronellol using a divergent diastereoselective approach. Key steps include a highly diastereoselective enamine/enal cycloaddition and the selective reduction of masked aldehyde functionalities by ionic hydrogenation.",10.1021/jo400884g,2013-06-21,0.6091787521404187
Synthesis,A Diastereoselective Route to Benzoannelated Bridged Sultams,"Abstract A practical diastereoselective method for the synthesis of benzoannelated tri- and tetracyclic bridged sultams has been developed. The synthetic route employs widely available, substituted o-iodoanilines and is based on intramolecular Michael addition followed by cycloalkylation with α,ω-dihaloalkanes, or vice versa. The target compounds were isolated in good yields and the diastereoselectivity of the reaction could be easily controlled by the order of Michael addition and cycloalkylation steps.",10.1055/a-1531-2176,2021-06-17,0.6091749298576182
Organic Letters,"Highly Efficient, Enantioselective Synthesis of (+)-Grandisol from a <i>C</i><sub>2</sub>-Symmetric Bis(α,β-butenolide)","[reaction: see text] A new, very efficient, enantioselective synthesis of the sexual attracting insect pheromone (+)-grandisol has been developed, in which the key step is the double [2 + 2] photocycloaddition of ethylene to a bis(alpha,beta-butenolide) readily available from D-mannitol. The C2 symmetry of the substrate and the appropriate protection of the central diol unit are the crucial features for the high diastereofacial discrimination during the cycloaddition process.",10.1021/ol991261k,2000-01-01,0.609169874420239
Journal of Organic Chemistry,Total Synthesis of (+)-Paucidactine D,"The first total synthesis of (+)-paucidactine D ( 4 ) is detailed from the pentacyclic intermediate 13 . The approach features two bridging cyclizations with the first being a SmI 2 -mediated intramolecular C21–C2 free radical cyclization to access the highly substituted bicyclo[2.2.2]octane core ring system. A subsequent intramolecular S N 2 displacement reaction was used to establish the C11–O bond of the bridging C11–OC(O)–C3 six-membered lactone. Central to the assemblage of the underlying Aspidosperma skeleton of 13 is a powerful [4 + 2]/[3 + 2] cycloaddition cascade of 1,3,4-oxadiazole 15, which provided the highly functionalized pentacyclic ring system in one step as a single diastereomer. The efforts combined with our past studies now represent the divergent total syntheses of members of eight distinct naturally occurring alkaloid classes from the same common intermediate 13, with each implementing a different late-stage core strategic bond formation.",10.1021/acs.joc.5c00984,2025-05-28,0.6091441802220805
Tetrahedron,"A novel synthesis of α- and β-halonaphthalenes via regioselective ring cleavage of aryl(gem-dihalocyclopropyl)methanols and its application to total synthesis of lignan lactones, justicidin e and taiwanin c",,10.1016/s0040-4039(00)97197-1,1990-01-01,0.6091434939842256
Journal of the American Chemical Society,An Asymmetric Synthesis of the Tricyclic Core and a Formal Total Synthesis of Roseophilin via an Enyne Metathesis,"A formal synthesis of roseophilin, a novel pentacyclic structure possessing significant antitumor activity, starting from 3-cycloundecenylcarboxylic acid has been completed. The acid was converted diastereoselectively to the corresponding menthol ester via the ketene which, in turn, provided ( S )-3-cycloundecenylcarboxaldehyde. Diastereoselective propargylation with propargyltriphenylstannane promoted by an asymmetric boron reagent prepared in situ from boron tribromide and the bis- p -toluenesulfonamide of ( S,S )-stilbenediamine gave (1 S,1‘ R )-1-cycloundec-2‘-enylbut-3-yn-1-ol which set the stage for the key metathesis reaction. Platinum-catalyzed enyne metathesis via a formal [2 + 2] cycloaddition to a cyclobutene followed by conrotatory ring opening created the corresponding bicyclo[10.2.1]pentadeca-1(15),2-diene. Regioselective epoxidation of the less reactive double bond of the 1,3-diene was accomplished by 1,4-bromohydrin formation followed by base. Cuprate opening regio- and stereospecifically installed the isopropyl substituent. Standard procedures converted this intermediate to (1 R,12 R,13 R,15 R )-13-( tert -butyldimethylsiloxy)-15-isopropylbicyclo[10.2.1]pentadecane-3,14-dione. This diketone was converted to the corresponding unstable pyrrole by condensation with ammonium acetate, and the pyrrole nitrogen immediately alkylated with SEM-chloride. The formal synthesis was completed by conversion of the siloxy group to the corresponding ketone which previously had been condensed with the heterocyclic side chain to complete a synthesis of roseophilin. By having access to the tricyclic core asymmetrically for the first time, this route provides the opportunity to establish the absolute configuration of the natural product.",10.1021/ja9941781,2000-04-01,0.6091412525732877
Tetrahedron,"Bismetalated derivatives of thioacids. Synthons for generation of β-hydroxy thioacids. A novel, convenient route to γ and δ thiolactones.",,10.1016/s0040-4039(01)93550-6,1979-01-01,0.6091393336878426
Synlett,"Asymmetric Synthesis of Tetrasubstituted Tetrahydrofuran, 2-Epigoniothalesdiol, Employing Stereoselective Hydrogenation","All articles of this category An efficient and stereodefined process is described for the preparation of a 3,4-dihydroxy-2,5-disubstituted tetrahydrofuran ring with the contiguous stereogenic centers and the asymmetric synthesis of 2-epigoniothalesdiol is also reported by featuring the elaboration of the functionalized homochiral lactone derived from C 2 -imide. goniothalesdiol - tetrasubstituted tetrahydrofuran - stereoselective deoxygenation - hemiketal - trisubstituted γ-lactone",10.1055/s-1999-2993,1999-12-01,0.6091278988056981
Journal of Organic Chemistry,β-Hydroxy-γ-lactones as Chiral Building Blocks for the Enantioselective Synthesis of Marine Natural Products,"The enantioselective synthesis of trans-(+)-laurediol, (2S,3S,5R)-5-[(1R)-1-hydroxy-9-decenyl]-2-pentyltetrahydro-3-furanol, and (2S,3S,5S)-5-[(1S)-1-hydroxy-9-decenyl]-2-pentyltetrahydro-3-furanol are described. In addition, a formal synthesis of trans-(-)-kumausyne is also developed. All the synthetic procedures have in common the use of enantiomerically enriched beta-hydroxy-gamma-lactones, easily available by Sharpless asymmetric dihydroxylation (AD) from the suitable beta,gamma-unsaturated ester. The use of Katsuki-Sharpless asymmetric epoxidation (AE) as an additional enantioselective reaction provides cyclic compounds of high enantiomeric purity.",10.1021/jo0057194,2001-01-17,0.6091141547490797
Journal of Organic Chemistry,"Asymmetric Synthesis of 1,2,3-Trisubstituted Cyclopentanes and Cyclohexanes as Key Components of Substance P Antagonists","An efficient asymmetric synthesis of 1,2,3-trisubstituted cyclopentanes and cyclohexanes is described. Three methods were developed for the preparation of the 2,3-disubstituted cyclopentenones and cyclohexenones, which are key achiral building blocks. These intermediates are reduced catalytically with (R)-2-methyloxazaborolidine in high yield (82-98%) and excellent ee (89-96%). Directed reduction of the chiral allylic alcohols using Red-Al gives exclusively the 1,2-anti stereochemistry (>99:1). Epimerization of the ester center followed by saponification/crystallization affords the desired hydroxyacids in good yield (65-70%) and in high enantiomeric excess (>99%).",10.1021/jo025883m,2002-07-18,0.6091139026925946
Organic Letters,Synthetic Studies on Taxol:  Highly Stereoselective Construction of the Taxol C-Ring via S<sub>N</sub>2‘ Reduction of an Allylic Phosphonium Salt,"[reaction: see text] The highly stereoselective construction of the C3 stereogenic center of the taxol C-ring is described. The trans isomer at the C3-C8 position of the taxol C-ring, which is required for the total synthesis, as well as its diastereomeric cis isomer were successfully synthesized with highly diastereoselective S(N)2' reduction of the allylic phosphonium salts.",10.1021/ol0608606,2006-06-07,0.6091075377850572
Tetrahedron,Synthesis of taxoids 3. A novel and efficient method for preparation of taxoids by employing cis-glycidic acid,,10.1016/s0040-4039(98)01124-1,1998-07-01,0.6091063006284244
Tetrahedron,A new approach to 1-deoxy-azasugars: Asymmetric synthesis of deoxymannojirimycin,,10.1016/0040-4039(96)00041-x,1996-02-01,0.6091003672491145
European Journal of Organic Chemistry,Highly Selective Three‐Step Synthesis of Rhein in Chloroaluminate Molten Salt: Preclusion of the Hayashi Rearrangement,"Abstract An expeditious, three‐step synthesis of rhein ( 2 ) was optimized starting from bis( N , N ‐diethyl)‐5‐methoxybenzene‐1,3‐dicarboxamide. The key final step, involving deprotection/cyclization of ortho ‐benzoylbenzoic acid 9 in acidic chloroaluminate molten salts, yielded the desired natural product with high selectivity and good overall yield by precluding the competitive Hayashi rearrangement.(© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2009)",10.1002/ejoc.200900960,2009-11-03,0.609080823630052
Synlett,A Stereocontrolled Synthesis of Methyl (-)-Nonactate,"A stereoselective synthesis of methyl (-)-nonactate is described. (E)-γ-Triethylsilyloxyalkene 13 generated from sulfone 10 and (S)-2-benzyloxypropanal underwent intramolecular iodo­etherification in the presence of silver carbonate to provide cis-2,5-disubstituted tetrahydrofuran 8 as a key intermediate.",10.1055/s-2003-37129,2003-01-01,0.6090800904160013
Journal of the American Chemical Society,"Total Syntheses of Durgamone, Nakorone, and Abudinol B via Biomimetic Oxa- and Carbacyclizations","The first biomimetic total syntheses of ent -nakorone, ent -durgamone, and ent -abudinol B were accomplished by combining features of tandem polyepoxide cyclization with biomimetic polyene cyclization. The present biomimetic synthesis route offers efficient access to these marine natural products. In addition, the synthesis of the tetrasubstituted alkene of ent -abudinol B demonstrates the application of palladium-catalyzed cross-coupling of two different polycyclic ketones via the corresponding vinyl triflates, followed by partial hydrogenation of the resulting conjugated diene.",10.1021/ja068826+,2007-01-17,0.6090780519061341
Organic Letters,Biomimetic Synthesis and Proposal of Relative and Absolute Stereochemistry of Heronapyrrole C,"The first synthesis of (-)-heronapyrrole C, the enantiomer of a unique farnesylated 2-nitropyrrole natural product is described. With none of the chiral centers of heronapyrrole C originally assigned, we proposed the most likely natural configuration on the basis of a putative biosynthetic pathway. The key step of the synthesis is a biomimetic polyepoxide cyclization cascade to establish the bis-THF moiety. Thus, (-)-heronapyrrole C is synthesized in eight steps from commercially available starting materials.",10.1021/ol300954s,2012-07-20,0.609075991354031
Angewandte Chemie International Edition,Total Synthesis of Lobatamides A and C,"The total synthesis of lobatamides A (1 a) and C (1 c) via a common bislactone intermediate is reported. The allylic aryl moiety including a trisubstituted Z-olefin was constructed by hydroboration of a 1,1-disubstituted allene and subsequent Migita-Kosugi-Stille coupling. Although the seco acid proved to be highly unstable even in the presence of weak bases, Zhao macrolactonization under acidic conditions via the α-acyloxyenamide successfully provided the common bislactone intermediate. Hydrozirconation-iodination of the terminal alkyne and subsequent copper-mediated coupling with primary amides proceeded successfully in the presence of the sensitive bislactone framework. The developed synthetic route enables the late-stage installation of enamide side chains, which are crucial structures for V-ATPase inhibition.",10.1002/anie.202402335,2024-03-08,0.6090759901830588
European Journal of Organic Chemistry,An Improved Synthesis of Ionizable Lipids D‐Lin‐KC2‐DMA and D‐Lin‐MC3‐DMA,"Considerable interest exists in ionizable lipids (ILs) for the delivery of nucleic acid therapeutics. While not a component of a yet‐approved medication, lipid KC2 is especially competent for the delivery of plasmid DNA, consequently it is in high demand on the part of research laboratories worldwide. Lipid MC3, a component of Onpattro, is a benchmark against which the efficacy of new ILs is evaluated. A new route to KC2 and MC3 through the double alkylation of TosMIC with linoleyl tosylate is described. The new synthesis avoids problematic reactions, proceeds in higher overall yield relative to the literature one, and in the case of KC2, involves three fewer steps.",10.1002/ejoc.202500592,2025-09-21,0.6090643235365715
Organic Letters,Brønsted-Acid-Catalyzed (3+2)-Cycloannulation of In-Situ-Generated 3-Methide-3<i>H</i>-pyrroles: Asymmetric Synthesis of Cyclopenta[<i>b</i>]pyrroles,"An organocatalytic, highly enantioselective addition of cyclic enamides to in-situ-generated 3-methide-3 H -pyrroles with subsequent cyclization and elimination has been developed. This protocol represents a novel and straightforward route toward polycyclic cyclopenta[ b ]pyrroles with high yields and excellent enantioselectivity. Central to the success is the formation of a chiral, hydrogen-bonded 3-methide-3 H -pyrrole upon phosphoric-acid-catalyzed dehydration of the starting 1 H -pyrrol-3-yl carbinol that reacts with the enamide in a stepwise cycloannulation process.",10.1021/acs.orglett.0c03452,2020-11-11,0.6090596371029039
Journal of Organic Chemistry,"Stereospecific Synthesis of Highly Substituted Piperazines via an One-Pot Three Component Ring-Opening Cyclization from <i>N</i>-Activated Aziridines, Anilines, and Propargyl Carbonates","A simple and efficient one-pot three-component synthetic route to highly substituted and functionalizable piperazines in high yields with excellent stereoselectivity (de, ee >99%) is reported. The S N 2-type ring-opening of N -activated aziridines by anilines followed by Pd-catalyzed annulation with propargyl carbonates gives rise to the final piperazine products.",10.1021/acs.joc.8b02259,2018-10-26,0.6090585845201487
Synlett,Total Synthesis of (+)-Eburnamonine,The enantiospecific total synthesis of vinca alkaloid (+)-eburnamonine is accomplished from l -ethyl lactate. Key feature of the synthesis is the construction of the chiral quaternary center involving a Johnson–Claisen rearrangement and assembly of the pentacyclic core by the Pictet–Spengler reaction and ring-closing metathesis.,10.1055/s-0031-1291143,2012-05-14,0.6090561642937611
Journal of Organic Chemistry,"Aromatization of 1,6,7,7a-Tetrahydro-2<i>H</i>-indol-2-ones by a Novel Process. Preparation of Key-Intermediate Methyl 1-Benzyl-5-methoxy-1<i>H</i>-indole-3-acetate and the Syntheses of Serotonin, Melatonin, and Bufotenin","Imine 7 of 1,4-cyclohexanedione mono-ethylene ketal 6 was reacted with maleic anhydride, affording the cyclized adduct 8. Methyl esterification of 8, accompanied by transacetalization, led to the dihydrooxindole derivative 10. Aromatization of 10 was then accomplished with POCl(3), leading directly to the key-intermediate title compound 11 in 74% yield from ketone 6. Serotonin, melatonin, and bufotenin were then obtained by standard reactions.",10.1021/jo0110597,2002-03-07,0.6090388443648654
Organic Letters,Asymmetric Total Synthesis of Batzelladine D,"[formula: see text] The first enantioselective total synthesis of a batzelladine alkaloid is described. The central reaction in the synthesis of (-)-batzelladine D (2) is a tethered Biginelli condensation of a guanidine aldehyde and an acetoacetic ester to generate a 7-substituted-1-iminohexahydropyrrolo-[1,2-c]pyrimidine intermediate having the anti stereochemistry of the methine hydrogens flanking the pyrrolidine nitrogen.",10.1021/ol991269u,1999-12-01,0.6090326552555575
Journal of the American Chemical Society,Asymmetric Total Synthesis of Neoxaline,"A first asymmetric total synthesis and determination of the absolute configuration of neoxaline has been accomplished through the highly stereoselective introduction of a reverse prenyl group to create a quaternary carbon stereocenter using (-)-3a-hydroxyfuroindoline as a building block, construction of the indoline spiroaminal via cautious stepwise oxidations with cyclizations from the indoline, assembly of (Z)-dehydrohistidine, and photoisomerization of unnatural (Z)-neoxaline to the natural (E)-neoxaline as the key steps.",10.1021/ja406657v,2013-08-11,0.6090252382297353
Tetrahedron,The synthesis of novel pyrrololactams and their boronate ester derivatives,,10.1016/j.tetlet.2016.11.047,2016-11-11,0.6090232222592684
Tetrahedron,Diastereoselective synthesis of phosphite triesters through a new bicyclic intermediate,,10.1016/0040-4039(95)02356-9,1996-02-01,0.6090210703220068
Tetrahedron,"A novel process for the synthesis of 3,5-diaryl-1,2,4-thiadiazoles from aryl nitriles",,10.1016/j.tetlet.2012.09.020,2012-09-14,0.6090117521736892
Tetrahedron,"Stereoselective route to N-methyl-2,3-CIS-dissubstituted piperidines",,10.1016/s0040-4039(00)80402-5,1988-01-01,0.609009553391247
Organic Letters,Studies toward Providencin: The Furanyl-Cyclobutanol Segment,"The furanocembranoid providencin remains an unconquered bastion, although the synthesis of 17-deoxyprovidencin─lacking a single -OH group─has been accomplished in the past. This paper describes a practical approach to a properly hydroxylated building block via an iridium-catalyzed photosensitized intramolecular [2 + 2] cycloaddition as the key step. While an attempt to convert this compound into providencin via RCAM failed, it might well be elaborated into the natural product by adopting the literature route.",10.1021/acs.orglett.3c00327,2023-02-27,0.6090089776487116
Organic Letters,Synthesis of the KLMN Fragment of Gymnocin-A Using Oxiranyl Anion Convergent Methodology,Synthesis of the KLMN fragment of gymnocin-A has been achieved by a [X + 2 + Y]-type convergent strategy involving the coupling of a K-ring triflate and an N-ring epoxy sulfone. Fusions of the L ring and the M ring were carried out by intramolecular SN2 substitution of a tertiary alcohol and reductive etherification to furnish the target molecule.,10.1021/ol500788c,2014-04-09,0.6090042215744229
Synthesis,Synthesis of Purinyl<i>homo</i>-Carbonucleoside Derivatives of 2-Benzylcyclopenta[<i>c</i>]pyrazol,"The first members of a new class of carbocyclic nucleoside analogs were synthesized via key intermediate (±)-(cis)-2-bencylcyclopenta[c]pyrazole-4,6-dimethanol, which was obtained from the easily prepared starting compound (±)-(exo,exo)-5,6-isopropylidenedioxy-4,5,6,7-tetrahydro-4,7-methano-2H-indazole by a reaction sequence in which the key step was a one-pot oxidative cleavage of glycol 9 and reduction of the resulting dialdehyde with NaBH4. Purine moieties were coupled by nucleophilic displacement following mesylation of the latter. The new compounds 15 and 17 are active against cytomagalovirus and varicella-zoster virus at subcytotoxical concentrations.",10.1055/s-2005-861831,2005-01-01,0.6090028266001082
Journal of the American Chemical Society,Enantioselective Staudinger Synthesis of β-Lactams Catalyzed by a Planar-Chiral Nucleophile,"The development of efficient methods for the stereoselective generation of beta-lactams is an important goal, due to their biological activity and their utility as synthetic intermediates. The Staudinger reaction, an overall [2 + 2] cycloaddition of a ketene with an imine, provides a nicely convergent route to this family of compounds. Nearly all studies to date of asymmetric variants of the Staudinger reaction have focused on the use of chiral auxiliaries to control the stereochemistry of the beta-lactam. In this report, we establish that a planar-chiral derivative of 4-(pyrrolidino)pyridine serves as a very effective enantioselective catalyst for the Staudinger beta-lactam synthesis, coupling a range of symmetrical and unsymmetrical ketenes with an array of imines with very good stereoselection and yield.",10.1021/ja012427r,2002-02-01,0.6089880700886406
Tetrahedron,New synthetic routes to β-hydroxyselenides and β-azidoselenides.,,10.1016/s0040-4039(01)86390-5,1979-01-01,0.608985706800842
Tetrahedron,A novel synthetic approach towards the AB-ring system of 9-azasteroids,,10.1016/s0040-4039(00)00020-4,2000-03-01,0.6089840684808183
Organic Letters,A Concise Route to (−)-Kainic Acid,A concise route to (-)-kainic acid from enantiopure (+)-cis-4-carbobenzoxyamino-2-cyclopentenol has been devised by employing concurrent Chugaev syn-elimination and intramolecular ene reaction as the key step.,10.1021/ol006377r,2000-09-06,0.6089693163384211
Tetrahedron,Boranes in synthesis. 4. Hydroboration of enamines derived from 2-norbornanone. Synthesis of endo-3-(dialkylamino)-exo-2-norbornanols and endo-2-(dialkylamino)norbornanes,,10.1016/s0040-4039(00)77054-7,1994-07-01,0.6089590561939976
Journal of Organic Chemistry,Total Synthesis of Clavicipitic Acid and Aurantioclavine: Stereochemistry of Clavicipitic Acid Revisited,"The stereocontrolled total synthesis of clavicipitic acid and aurantioclavine from a common azepino[5,4,3-cd]-indole intermediate is reported. This key azepinoindole nucleus was constructed via a one-pot Heck/Boc-deprotection/aminocyclization process from the 4-iodotryptophan derivative, which was assembled by a Pd-catalyzed indole synthesis procedure. After two or three additional deprotection steps from the azepinoindole intermediates, (-)-trans- and (-)-cis-clavicipitic acid were prepared. The syntheses of both (-)- and (+)-aurantioclavine were achieved with the same azepinoindole intermediates utilizing the Barton decarboxylation reaction as the key step to remove the stereohindered carboxylic acid. During the course of our synthesis, mis-assigned configurations of the synthesized clavicipitic acids and their derivatives in the literature were identified. Extensive studies including 2D-NMR study, X-ray diffraction analysis, titration experiment, and Rf value comparison unambiguously confirmed the new configuration assignment. The trans and cis configuration assignments of the synthesized clavicipitic acids and their derivatives in the past literature should be switched.",10.1021/jo101506c,2010-10-21,0.6089575819581368
Tetrahedron,The synthesis of polarofacial spacer molecules: a new twist in the coupling of ring strained olefins with oxadiazoles.,,10.1016/s0040-4039(00)85989-4,1991-04-01,0.6089561522455854
Journal of Organic Chemistry,Formal Total Synthesis of the Polyketide Macrolactone Narbonolide,[reaction: see text] An improved synthesis of (3S)-3-dihydronarbonolide is reported that constitutes a formal total synthesis of the 14-membered macrolactone antibiotic narbonolide. The key step was an intramolecular Nozaki-Hiyama-Kishi coupling to accomplish macrocyclization in improved yield. The high level of convergence will also allow us to rapidly synthesize narbonolide analogues for the study of enzymes in the pikromycin biosynthetic pathway.,10.1021/jo050924a,2005-08-06,0.6089540881337845
Tetrahedron,Homo-Brook route to benzazocenols and congeners via allylsilane-derived aziridines,,10.1016/s0040-4039(01)02018-4,2001-12-01,0.6089458779154787
European Journal of Organic Chemistry,Synthesis of Chiral Aziridines from Glycals: Application in the Synthesis of a Piperidine–Azepine Fused Derivative,"Vicinal chloroamines derived from glycals have been converted into the corresponding chiral aziridines. Although the formation of a tetrahydrofuran derivative is also possible, reaction conditions were developed to give the azirdines exclusively. One of the aziridines is closely related to a compound used in the synthesis of an advanced intermediate en route to Zanamivir, an antiviral agent. Furthermore, one of the aziridines was converted into a piperidine–azepine fused derivative.",10.1002/ejoc.201700624,2017-06-20,0.6089361311093715
Organic Letters,Selective Fowler Reductions:  Asymmetric Total Syntheses of Isofagomine and Other 1-Azasugars from Methyl Nicotinate,"[figure: see text] An efficient, high-yielding strategy has been developed for the asymmetric synthesis of 1-N-iminosugars (1-azasugars), a new class of glycosidase inhibitors with promising biomedical applications. A highly regioselective procedure for the 1,2-reduction of substituted pyridines was employed to transform methyl nicotinate into several representative 1-azasugars.",10.1021/ol006810x,2000-12-21,0.6089328438373626
Tetrahedron,Studies directed toward the total synthesis of tetronolide 1. An enantioselective synthesis of the octahydronaphthalene unit,"An efficient enantioselective route to the octahydronaphthalene unit present in tetronolide (1), the stereochemically complex aglycone common to the tetrocarcins, a novel group of antitumor substances, is described. The sequence employs the intramolecular Diels-Alder reaction to control the relative stereochemistry present on the trans decalin ring system, and incorporates a masked acylating agent which should permit coupling of the two key fragments 2 and 3 as demonstrated by reaction of pentaene 4 with methanol and a model α-hydroxy ester.",10.1016/s0040-4039(00)79871-6,1991-08-01,0.6089299570091924
Organic Letters,Total Synthesis of Pacidamycin D by Cu(I)-Catalyzed Oxy Enamide Formation,"The first total synthesis of pacidamycin D, which is expected to be a good candidate as an antibacterial agent against P. aeruginosa, is described. The key elements of our approach feature an efficient and stereocontrolled construction of the Z-oxyvinyl iodide and copper-catalyzed cross-coupling with the tetrapeptide carboxamide.",10.1021/ol202124b,2011-09-08,0.6089137594875523
European Journal of Organic Chemistry,"Synthesis of Optically Active Selenium‐Containing Isotryptophan, Homoisotryptophan, and Homotryptophan",Abstract Selenoisotryptophan and its higher homologues were synthesized by Sonogashira coupling of iodophenyl methyl selenide and alkynyloxazolidines followed by iodocyclization as the key step. Sonogashira coupling of 3‐iodobenzoselenophene with ethynyloxazolidine allowed the synthesis of selenohomotryptophan.,10.1002/ejoc.201300352,2013-05-07,0.6089113140512026
Tetrahedron,A convenient and efficient route for the synthesis of amidecrownophanes via 1:1 macrocyclization of di(acid chloride) with diamine derivatives,,10.1016/j.tetlet.2007.02.097,2007-02-26,0.6089080656008139
Journal of Organic Chemistry,Synthesis of Puraquinonic Acid Ethyl Ester and Deliquinone via a Common Intermediate,Both compounds were prepared via a common intermediate. The key features included the direct synthesis of the indan skeleton and the radical addition to a quinone.,10.1021/jo020029g,2002-07-12,0.608904448826352
Journal of Organic Chemistry,"A Facile, Expeditious Route to the Benzooxabicyclo[3.2.1]octane System. Application to a Short, High-Yield Synthesis of Filiformin","A facile and efficacious route to the benzooxabicyclo[3.2.1]octane system has been developed and applied to a synthesis of filiformin (1). The cycloaddition of ethylene to the methoxychromone 13 furnished the oxetanol 14 through a tandem cycloaddition and gamma-hydrogen abstraction sequence. Lithium aluminum hydride reduction to the diol 15 followed by acid-catalyzed rearrangement produced benzooxabicyclooctanone (16), arising from exclusive external bond migration. Similarly, ethoxychromone (17) under the same sequence of reactions afforded the homologous bridged ketone 20. For the synthesis of filiformin (1), methoxychromone 24 on ethylene cycloaddition followed by reduction of resultant oxetanol 25 with lithium aluminum hydride furnished diol 10. Acid-catalyzed rearrangement of 10 provided the bridged ketone 11 which was brominated to give 26. This bromo ketone had previously been converted to filiformin (1), and also aplysin 9, and hence, the present work represents a short, high-yield formal synthesis of these sequiterpenes from a single starting material.",10.1021/jo952184j,1996-01-01,0.6088745845844439
Synthesis,A Short and Efficient Synthesis of (S)-(+)-2-(Hydroxymethyl)-6-piperidin-2-one,A concise synthesis of (S)-(+)-2-(hydroxymethyl)-6-piperidin-2-one is described that employs l-aspartic acid as chiral pool starting material and Wittig reaction as the key step.,10.1055/s-0029-1218823,2010-06-18,0.6088745539576295
Journal of Organic Chemistry,Enantioselective Syntheses of (−)- and (+)-Monomorine I,A concise enantioselective total synthesis of unnatural (-)-monomorine I has been achieved starting from lactam 2 in 54% overall yield. Natural (+)-monomorine I was also synthesized.,10.1021/jo800593n,2008-05-29,0.6088686840274604
Organic Letters,Enantioselective Total Synthesis of (−)-Walsucochin B,"The first enantioselective total synthesis of the structurally unique nortriterpenoid (-)-walsucochin B has been accomplished through the cationic polyolefin cyclization initiated by chiral epoxide. The core framework and the stereocenters in the natural product were all constructed in this step. A site-selective, late-stage free-radical halogenation and Seyferth-Gilbert homologation was adopted to install the acetylene moiety to synthesize the phenylacetylene. The absolute configuration of walsucochin B was confirmed through enantioselective total synthesis.",10.1021/ol500553x,2014-03-26,0.6088640654015485
Organic Letters,Flexible Strategy for the Synthesis of Pyrrolizidine Alkaloids,"A general strategy for the production of pyrrolizidine alkaloids is described, starting from intermediate (+)-9. The key features are diastereoselective dihydroxylation, inversion at the ring junction by hydroboration of an enamine, and ring closure to form the bicyclo ring system. This route is attractive because of its brevity and versatility; four natural products were prepared with differing stereochemistry and substitution patterns. Finally, this work allowed assignment of the absolute stereochemistry of 2,3,7-triepiaustraline and hyacinthacine A 7.",10.1021/ol801415d,2008-07-18,0.6088616809986078
Journal of the American Chemical Society,Stereocontrolled Total Synthesis of (+)-Paraherquamide B,"The convergent stereocontrolled, asymmetric total synthesis of (+)-paraherquamide B is described. Key features of this synthesis include (1) an improved procedure to effect reduction of unprotected oxindoles to indoles; (2) a complex application of the Somei/Kametani coupling reaction; (3) a high-yielding and entirely stereocontrolled intramolecular S N 2‘ cyclization reaction that constructs the core bicyclo[2.2.2] ring system; (4) a mild Pd(II)-mediated cyclization reaction that constructs a complex tetrahydrocarbazole; and (5) the chemoselective reduction of a highly hindered tertiary lactam in the presence of an unhindered secondary lactam, utilizing precoordination of the more reactive secondary lactam to triethylaluminum.",10.1021/ja952666c,1996-01-01,0.6088606395036161
Tetrahedron,"Reductive cyanation: A key step for a short synthesis of (−)-(2S,3S)-3-hydroxyproline",,10.1016/s0040-4039(98)01133-2,1998-08-01,0.6088576320627122
Tetrahedron,"A short enantioselective synthesis of (+)-eleutherin, (+)-allo-eleutherin and a formal synthesis of (+)-nocardione B",,10.1016/j.tetlet.2008.08.065,2008-08-24,0.6088555152793051
Tetrahedron,Easy two-step synthesis of new tris(perfluoroalkylphenyl)phosphites,,10.1016/s0040-4039(98)02134-0,1998-12-01,0.6088533750489773
Journal of the American Chemical Society,Enantioselective Total Synthesis of (+)-Taxusin,"For the total synthesis of (+)-taxusin, the AC-ring fragment 8 was prepared from an optically active 2-bromo-3-siloxycyclohexenecarbacetal 5 via 4 steps and was converted to the dienol silyl ether 13 . The thus-obtained 13 underwent B-ring cyclization in the presence of Me 2 AlOTf to produce the ABC endo -tricarbocycle 14 having C9α, C10β-substituents, which was converted to the cyclopropyl ketone 21a . Introduction of C19 methyl via reductive cleavage of the cyclopropane ring under Birch conditions and successive in situ treatment of the resulting enol with methanol gave the C3α-protonated ketone 24 . Next, 24 was converted to the allylsilane 29, which was then oxidized with m -CPBA to produce the fully functionalized taxusin carbon skeleton. Finally, removal of the silyl protecting groups followed by acetylation completed the total synthesis of (+)-taxusin.",10.1021/ja984250f,1999-03-20,0.6088514069728366
Tetrahedron,"Synthesis of enantiopure (S)-7-hydroxy-3-amino-3,4-dihydro-2H-1-benzopyran en route to (+)-scyphostatin",,10.1016/j.tetlet.2007.01.006,2007-01-08,0.6088429946884246
Journal of Organic Chemistry,Formal Synthesis of (±)-Pentalenolactone A Methyl Ester,"We report the formal synthesis of (±)-pentalenolactone A methyl ester from simple 2-methoxyphenol. The key features of our route are as follows: a Diels–Alder reaction of masked o -benzoquinone to assemble the functionalized bicyclo[2.2.2]octenone, a continuous-flow oxa-di-π-methane rearrangement for building the diquinane core (AB ring), and an oxidative cleavage/oxidation sequence for annulation of the δ-lactone (C ring).",10.1021/acs.joc.9b01349,2019-07-12,0.6088337508168913
Tetrahedron,A flexible synthesis of novel homoharringtonine ester chain,,10.1016/j.tetlet.2015.12.012,2015-12-12,0.6088307555382863
Synthesis,A Convenient Synthesis of Trifluoroacetamide Derivatives of Diaza[3<sub>2</sub>]cyclophanes and Triaza[3<sub>3</sub>]cyclophanes,"The diaza[32]cyclophane skeleton has been constructed by the bis-N-alkylation of 1,4-bis[(4-nitrophenylsulfonylamino)methyl]benzene with 1,4-bis(halomethyl)benzene in the presence of sodium hydride. The 4-nitrophenylsulfonyl (Ns) amides in the bridge chains of the cyclophane were effectively deprotected by sodium ethanethiolate and the resulting free amine moieties were reprotected as the trifluoroacetamide under mild conditions to afford 3,7-bis(trifluoroacetyl)-3,7-diaza-1,5(1,4)-dibenzenacyclooctaphane in 26% overall yield. This Ns-amide method has also been applied for the preparation of a higher homologue, the trifluoro­acetamide derivative of triaza[33]cyclophane, 3,5,7-tris(trifluoroacetyl)-3,7,10-triaza-1,5(1,3,5)-dibenzenabicyclo[3.3.3]undeca­-phane, in 18% overall yield. Thus, the present procedure provides a convenient synthetic route to azacyclophane derivatives possessing trifluoroacetamide groups in the bridge chains.",10.1055/s-2007-1000825,2007-12-20,0.6088116255325655
Tetrahedron,Stereoselective synthesis of novel five-membered homoazasugars. A convenient route to all-cis tetrasubstituted pyrrolidines,,10.1016/j.tetlet.2006.10.128,2006-11-22,0.6088025327443042
Journal of the American Chemical Society,Total Synthesis and Biological Evaluation of the Nakijiquinones,"The Her-2/Neu receptor tyrosine kinase is vastly overexpressed in about 30% of primary breast, ovary, and gastric carcinomas. The nakijiquinones are the only naturally occurring inhibitors of this important oncogene, and structural analogues of the nakijiquinones may display inhibitory properties toward other receptor tyrosine kinases involved in cell signaling and proliferation. Here, we describe the first enantioselective synthesis of the nakijiquinones. Key elements of the synthesis are (i) the reductive alkylation of a Wieland-Miescher-type enone with a tetramethoxyaryl bromide, (ii) the oxidative conversion of the aryl ring into a p-quinoid system, (iii) the regioselective saponification of one of the two vinylogous esters incorporated therein, and (iv) the selective introduction of different amino acids via nucleophilic conversion of the remaining vinylogous ester into the corresponding vinylogous amide. The correct stereochemistry and substitution patterns are completed by conversion of two keto groups into a methyl group and an endocyclic olefin via olefination/reduction and olefination/isomerization sequences, respectively. This synthesis route also gave access to analogues of nakijiquinone C with inverted configuration at C-2 or with an exocyclic instead of an endocyclic double bond. Investigation of the kinase-inhibiting properties of the synthesized derivatives revealed that the C-2 epimer 30 of nakijiquinone C is a potent and selective inhibitor of the KDR receptor, a receptor tyrosine kinase involved in tumor angiogenesis. Molecular modeling studies based on the crystal structure of KDR and a model of the ATP binding site built from a crystal structure of FGF-R revealed an insight into the structural basis for the difference in activity between the natural product nakijiquinone C and the C-2 epimer 30.",10.1021/ja011413i,2001-11-01,0.6087805894371544
Journal of Organic Chemistry,Total Synthesis of the Macrocyclic <i>N</i>-Methyl Enamides Palmyrolide A and 2<i>S</i>-Sanctolide A,"Full details of the total syntheses of the initially reported and revised structures of the neuroprotective agent palmyrolide A are reported. The key macrocyclization step was achieved using a sequential ring-closing metathesis/olefin isomerization reaction. Furthermore, the total synthesis of the related macrolide (2S)-sanctolide A is reported. The synthesis used key elements from the synthesis of palmyrolide A, including the RCM/olefin isomerization sequence. The synthetic work described herein serves to facilitate the assignment of stereochemistry of the natural product sanctolide A and demonstrates the utility of this approach for the synthesis of macrocyclic tertiary enamide natural products.",10.1021/jo502238r,2014-11-04,0.6087713413853578
Tetrahedron,"A concise synthesis of the bioactive meroterpenoid natural product (±)-liphagal, a potent PI3K inhibitor",,10.1016/j.tetlet.2009.07.019,2009-07-10,0.6087691627418244
Angewandte Chemie International Edition,Concise Enantioselective Synthesis of (+)‐FR66979 and (+)‐FR900482: Dimethyldioxirane‐Mediated Construction of the Hydroxylamine Hemiketal,"The remarkable one-step deprotection/oxidative cyclization of an eight-membered-ring aminoketone 1 in the presence of dimethyldioxirane gives rise to the unique hydroxylamine hemiketal ring system of FR66979 (2) and FR900482 (3), clinically important antitumor antibiotics. The concise 33-step enantioselective synthesis of 3 is the shortest route reported to date.",10.1002/anie.200290015,2002-12-12,0.6087546568736645
Journal of Organic Chemistry,First Total Synthesis of (±)-Melinonine-E and (±)-Strychnoxanthine Using a Radical Cyclization Process as the Core Ring-Forming Step,"The first total synthesis of (±)-melinonine-E and (±)-strychnoxanthine is described. The key common step for the synthesis of both alkaloids is the elaboration of the 2-azabicyclo[3.3.1]nonane nucleus (D and E rings) by a radical carbocyclization, using an α-carbamoyldichloromethyl radical as a donor. The closure of the C ring by a Bischler−Napieralski cyclization, followed by an epimerization process to gain the axial nitrile 20, and appropriate reduction transformations afforded pentacyclic alcohol 23 . This alcohol was converted into either (±)-melinonine-E ( 1 ) or (±)-strychnoxanthine ( 2 ) by means of a palladium black dehydrogenation of the C ring or a SeO 2 oxidation of the corresponding acetate 25, respectively.",10.1021/jo971148c,1998-01-27,0.6087422840938812
Synlett,Development of an Efficient Synthetic Process for Irisquinone,"Abstract Irisquinone is a tumor radiotherapy sensitizer and has been found to have broad-spectrum antitumor activity in recent years. The current acquisition method of extracting and purifying from semen irisis has greatly limited its wide application and activity study deeply. In this work an efficient route for the synthesis of the irisquinone was investigated to solve the source of it. The target compound was synthesized by 5-step reactions to Wittig reaction, reduction, oxidation, Wittig reaction, and oxidation using 3,5-dimethoxycarboxaldehyde as the starting material with an overall yield of 48%. The key factors such as the ratio of raw materials, temperatures, solvents, reaction times, and types of base for the main reactions were optimized. In addition, the deprotection and reduction were completed with Pd/C catalytic simultaneously when compound 2 was synthesized from compound 1. In the last reaction, the 3,5-dimethoxybenzene moiety of compound 4 was directly oxidized to 6-methoxy-1,4-benzoquinone by K3[Fe(CN)6]/H2O2 without the need to selectively remove the methyl protecting group, which were the innovative points in the experimental route design of the irisquinone synthesis. This work has opened new perspectives for the artificial synthesis and the development of irisquinone.",10.1055/s-0042-1751560,2024-02-16,0.6087335375109393
Organic Process Research & Development,Synthesis of a Serinamide by Aminolysis of an N-Unsubstituted α-Amino Ester,l -2-Amino-3-hydroxy- N -pentylpropanamide ( 1 ) was readily prepared and isolated as its oxalate salt in 81% yield and >99% ee through a “one-pot” process from l -serine methyl ester ( 4 ).,10.1021/op960044l,1997-03-01,0.6087288754880202
Synlett,An Efficient Formal Total Synthesis of (±-Stypoldione via Photochemically Triggered Biomimetic Cyclizations of Terpenoid Polyalkenes,"All articles of this category A novel and efficient synthesis of stypoldione, an antitumoral marine toxin, is accomplished by the application of photoinduced biomimetic cyclizations of terpenoid polyalkenes as the key step for the construction of the 6-6-6 tricyclic diterpene part of this natural product. electron transfer - photochemistry - biomimetic radical cyclization - radical cation - (±)-stypoldione synthesis",10.1055/s-1999-3110,1999-12-31,0.6087238150590517
Tetrahedron,"A concise asymmetric synthesis of 5,8-disubstituted indolizidine alkaloids. Total synthesis of (−)-indolizidine 209B",,10.1016/s0040-4039(02)02149-4,2002-11-01,0.6087237412751927
Organic Letters,Second-Generation Synthesis of the Polypropionate Subunit of Callystatin A Based on Regioselective Internal Alkyne Hydrostannation,[formula: see text] An improved route to the polypropionate segment of callystatin A is described in which the efficient directed hydrostannation of an internal alkyne and subsequent iodinolysis provides a key vinylic iodide intermediate.,10.1021/ol026791m,2002-10-01,0.6087088112342758
Tetrahedron,The reaction of photochemically generated α-hydroxyalkyl radicals with alkynes: a synthetic route to γ-butenolides,,10.1016/j.tetlet.2008.11.067,2008-11-26,0.60869159953282
Angewandte Chemie International Edition,"Enantioselective Synthesis of Oasomycin A, Part I: Synthesis of the C1–C12 and C13–C28 Subunits","Putting the pieces together: The total synthesis of the natural macrolide oasomycin A has been realized. Key fragment couplings include an anti-Felkin selective aldol addition (green), Kociensky–Julia olefinations (red), and competitive Weinreb amide acylation reaction (blue). The utility of the 4,5-diphenyloxazole as a carboxy surrogate and the late-stage macrolactonization affording the 42-membered macrocycle of oasomycin A are also described.",10.1002/anie.200603653,2006-12-08,0.6086763147634175
Organic Process Research & Development,A Safe and Efficient Process for the Synthesis of the Inhalation Anesthetic Sevoflurane,"A novel method for the synthesis of 1,1,1,3,3,3-hexafluoro-2-(fluoromethoxy)propane (sevoflurane) is described. Starting from commercially available 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP), the process involves a novel, safe and efficient fluoromethylation protocol in a two-step, one-vessel procedure. The method avoids many of the hazards and complications of the current process for sevoflurane manufacture. The new method is easily scaled up to afford 10-kg batches of 99.4% pure sevoflurane.",10.1021/op000207c,2000-09-21,0.6086680456040546
Journal of Organic Chemistry,A General Strategy for the Practical Synthesis of Nojirimycin <i>C</i>-Glycosides and Analogues. Extension to the First Reported Example of an Iminosugar 1-Phosphonate,"An efficient and versatile strategy for the synthesis of nojirimycin C-glycosides and related compounds with full stereocontrol is reported. The key steps of the process are the addition of organometallic reagents onto an L-sorbose-derived imine (13) followed by an internal reductive amination. The addition step, which controls the alpha- vs beta-configuration at the pseudoanomeric center in the final product, is highly diastereoselective (re-face addition), and the stereoselectivity can be effectively inverted by adding an external monodentate Lewis acid (si-face addition). The complete synthesis could be achieved in 10 steps only from commercially available 2,3;4,6-di-O-isopropylidene-alpha-L-sorbofuranose and provided alpha- or beta-1-C-substituted 1-deoxynojirimycin derivatives in 27-52% overall yield. The strategy was successfully extended to the first example of an iminosugar 1-phosphonate. The methodology provides access to a wide range of biologically relevant glycoconjugate mimetics in which the glycosidic function is replaced by an imino-C-glycosidic linkage.",10.1021/jo0203903,2002-09-04,0.6086588654856456
Synthesis,"A Novel Entry into a New Class of (Chromanone-pyrrolidine/pyrrolizidine/pyrrolo[1,2-c]thiazole/pyrrolo[1,2-a]isoquinoline)indane-1,3-dione Ring Systems through [3+2] Cycloaddition","A highly regioselective synthesis of novel dispiroheterocycles by the cycloaddition of azomethine ylide generated through a decarboxylative route from sarcosine/proline/thiazolidine-4-carboxylic­ acid/1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid and ninhydrin with the dipolarophile 3-arylidene-4-chromanone is described.",10.1055/s-2006-926347,2006-01-01,0.6086555115482907
Tetrahedron,"Efficient synthesis of pyrrolizidine and indolizidine derivatives using nickel-catalyzed cyclization of 1,3-diene and aldehyde: Formal total synthesis of (−)-Elaeokanine C",,10.1016/s0040-4039(97)00782-x,1997-06-01,0.6086551838568467
Tetrahedron,"Claisen self-condensation/decarboxylation as the key steps in the synthesis of C2-symmetrical 1,7-dioxaspiro[5.5]undecanes",,10.1016/j.tetlet.2005.07.073,2005-08-03,0.6086517413996757
Angewandte Chemie International Edition,Enantioselective Total Synthesis of the Polycyclic Guanidine‐Containing Marine Alkaloid (−)‐Batzelladine D,Addressing the marine core: The enantioselective total synthesis of the polycyclic guanidine-containing marine alkaloid (−)-batzelladine D has been accomplished using a convergent 14-step reaction sequence (longest linear sequence) in 10 % overall yield. The ability to accomplish the selective homolytic cleavage of an alkyl iodide in the presence of an azide circumvents the necessity for nitrogen-protecting groups.,10.1002/anie.200700840,2007-08-31,0.608650514554481
Tetrahedron,A new approach to indolizidine alkaloids: Asymmetric formal total synthesis of (−)-Swainsonine,,10.1016/0040-4039(95)00058-k,1995-02-01,0.6086474551424118
Synlett,A Highly Efficient Conversion of a Simple Derivative of the Amino Acid Proline into a Nearly Enantiomerically Pure N-Protected Allyl Amine: Use of Thionyl Chloride to Promote the Peterson Olefination,"A novel two-step conversion of an N-Boc methyl ester of the natural amino acid proline into highly enantioenriched N-Boc 2-vinylpyrrolidine is described. Key steps include (1) an SNi displacement of a methoxy group of the DIBAL-H adduct of the starting ester by the TMSCH2 group of the corresponding Grignard reagent, and (2) the use of thionyl chloride to promote the Peterson olefination of the resulting β-hydroxysilane bearing a stereocenter adjacent to the alcohol function. The overall transformation occurs with remarkable facility and virtually without loss of stereochemical integrity under mild conditions. The use of thionyl chloride in the elimination step is necessary because both basic and acidic conditions are incompatible with the Boc protecting group. In stark contrast to the standard Wittig olefination of the corresponding N-protected amino aldehyde, where 8-10% racemization (80-84% ee) occurs, only about 1% racemization (98% ee) was observed in this novel process.",10.1055/s-0031-1289536,2011-10-19,0.6086273014646763
Tetrahedron,"Macrocyclic renin inhibitors: Synthesis of a subnanomolar, orally active cysteine derived inhibitor",,10.1016/s0040-4039(00)61590-3,1993-10-01,0.6086232824710448
Journal of Organic Chemistry,Collective Syntheses of 8-Oxoprotoberberines via Sequential In(OTf)<sub>3</sub>-Catalyzed Cyclization and Pd(OAc)<sub>2</sub>-Catalyzed Heck Coupling,"Six 8-oxoprotoberberines were synthesized collectively in four steps with acceptable yields (14–19%), of which the products 8-oxopalmatine, 8-oxopseudopalmatine, 8-oxoberberine, and 8-oxopseudoberberine come from nature. The synthetic route was featured with the In(OTf) 3 -catalyzed cyclization and Heck coupling. Moreover, the syntheses of the natural products berberine, canadine, and iambertine were achieved via various reductions from 8-oxoberberine, which provided a concise approach to the syntheses of this kind of alkaloids.",10.1021/acs.joc.3c00419,2023-05-12,0.6086146195679196
Organic Process Research & Development,Streamlined Three-Step Telescope Enabled by a Nonaqueous Suzuki–Miyaura Cross-Coupling Reaction,"The process optimization of a key step in the synthesis of NLRP3 (nucleotide-binding domain and leucine-rich repeat-containing protein 3) agonist BMS-986299 is reported. The step is a convergent three-stage telescope featuring four discrete chemical transformations: a Pd-catalyzed Miyaura borylation, followed by a Suzuki–Miyaura cross-coupling, then a concurrent acid-mediated cyclization and THP (tetrahydropyran) cleavage. Through targeted process development focused on safety, sustainability, and robustness, we developed safer and more robust borylation conditions to generate an aryl boronate ester intermediate that is then taken into a nonaqueous Suzuki–Miyaura reaction via a streamlined telescoped sequence and a subsequent kinetic analysis-driven reactive crystallization to synthesize the imidazole-fused 2-aminoquinoline core of BMS-986299. Overall, the improvements discussed herein resulted in a greener, safer, and more robust process for the synthesis of this intermediate.",10.1021/acs.oprd.4c00138,2024-06-10,0.6086087644563958
European Journal of Organic Chemistry,"Total Synthesis of Carbazole Alkaloids – Ekeberginine, Harmandianamine A, and Furanoclausamine B",Abstract The anionic [4 + 2] annulation of 3‐substituted furoindolones with dimethyl maleate provides an expedient route for the synthesis of the title carbazole alkaloids. The employment of this strategy in combination with a Krapcho reaction/ retro ‐Kolbe–Schmitt reaction has culminated in the first total synthesis of the lactonic carbazoles harmandianamine A and furanoclausamine B and a brief total synthesis of ekeberginine from a prenylated furoindolone. An unusual fragmentation of an ester function during the annulation is also reported.,10.1002/ejoc.201301652,2014-01-15,0.6085942180016373
Tetrahedron,"Palladium-catalyzed synthesis of o-acetylbenzoic acids: a new, efficient general route to 2-hydroxy-3-phenyl-1,4-naphthoquinones and indolo[2,3-b]naphthalene-6,11-diones",,10.1016/s0040-4039(02)00990-5,2002-07-01,0.6085820285736264
Tetrahedron,Concise synthesis of moracin M using Appel mediated dehydration of a bioinspired endoperoxide,"A synthesis of moracin M using Appel dehydration of a biomimetic inspired endoperoxide and subsequent late stage aromatization, is described. A key 1,3-diene, obtained from a base-free Suzuki-Miyaura coupling, can undergo biomimetic oxidation to its endoperoxide, followed by dehydration under Appel conditions and aromatization to give a benzofuran, with subsequent deprotection then providing moracin M in only 4-steps. Alternatively, this 1,3‑diene can undergo aromatization and subsequent deprotection providing a synthetic route to resveratrol.",10.1016/j.tetlet.2022.154273,2022-11-25,0.6085777246231209
Organic Letters,Catalytic Asymmetric Synthesis of the Central Tryptophan Residue of Celogentin C,"[reaction: see text] Chiral phase-transfer catalyst 5 containing an electron-deficient trifluorobenzyl moiety promoted the alkylation of glycine derivative 6 with propargyl bromide 7a in good yield and excellent ee. The resulting propargyl glycine 8 was converted to 14, the central tryptophan residue of Celogentin C, in two steps, with the Pd-catalyzed heteroannulation as the key transformation. This method promises to be an efficient route for the preparation of tryptophan derivatives possessing substitution on the indole ring.",10.1021/ol035236x,2003-08-30,0.6085578982276499
Organic Process Research & Development,An Efficient Synthesis of (<i>R</i>)-2-Butyl-3-hydroxypropionic Acid,An efficient synthesis of ( R )-2-butyl-3-hydroxypropionic acid ( 1 ) via a classical resolution of (±)-2-butyl-3-hydroxypropionic acid ( 7 ) with ( R )-α-methylbenzylamine is described. (±)-2-Butyl-3-hydroxypropionic acid ( 7 ) was readily available from diethyl butylmalonate ( 2 ) in two steps. Results on the enantioselective enzymatic hydrolysis of 2 with pig liver esterase and α-chymotrypsin towards 1 are also described.,10.1021/op060199l,2006-12-14,0.6085568220906056
Tetrahedron,An asymmetric dihydroxylation route to enantiomerically pure norfluoxetine and fluoxetine,,10.1016/s0040-4039(02)00842-0,2002-06-01,0.6085518057038153
Journal of Organic Chemistry,Fluorescent Charge-Neutral Analogue of Xanthosine:  Synthesis of a 2‘-Deoxyribonucleoside Bearing a 5-Aza-7-deazaxanthine Base,"A concise route is described to prepare the 5-aza-7-deazapurine 2'-deoxyriboside (4), which presents the puADA hydrogen-bonding pattern, analogous to the hydrogen-bonding pattern presented by 2'-deoxyxanthosine (2). The route begins with the commercially available 1-alpha-chloro-2-deoxy-3-5-bistoluoyloxyribofuranose (10), which proves to be a versatile point of entry to beta-2'-deoxyribofuranosides. In the first step, 2-nitroimidazole (8) is coupled with 10 to yield intermediate 11. Reduction of the nitro group to an amino group yields 12, which is treated with phenyl isocyanatoformate to complete the nucleobase to yield 13. Removal of the toluoyloxy protecting groups of 13 yields the target nucleoside 4 in 40% overall yield in four steps. In an alternative strategy, convergent coupling of 14 with 10 under basic conditions was attempted but found to yield the heterocycle glycosylated at the undesired position. Compound 13 displays potentially useful fluorescence properties. After excitation at 250 nm, a solution of 13 in MeCN shows a fluorescence emission with a maximum at 410 nm. Furthermore, 13 is neutral at physiological pH, a property that it shares with natural nucleobases but not xanthosine itself, which is an acid with a pK(a) of ca. 5.6. Furthermore, as part of the design, 4 is made capable of presenting an unshared pair of electrons to the DNA minor groove.",10.1021/jo005743h,2001-06-30,0.6085509820461029
Journal of Organic Chemistry,Practical Asymmetric Preparation of Azetidine-2-carboxylic Acid,"[reaction: see text] Facile and straightforward syntheses of both enantiomers of azetidine-2-carboxylic acid are described. The syntheses depart from inexpensive chemicals and allow for the production, in five to six steps, of practical quantities of each enantiomer. Synthetic highlights include the construction of the azetidine ring using an intramolecular alkylation and the use of optically active alpha-methylbenzylamine as chiral auxiliary.",10.1021/jo0515881,2005-10-01,0.6085493832839256
Organic Letters,A Novel Synthesis of (−)-Huperzine A via Tandem Intramolecular Aza-Prins Cyclization–Cyclobutane Fragmentation,"The acetylcholinesterase inhibitor (-)-huperzine A was synthesized from (S)-4-hydroxycyclohex-2-enone in 17 steps by a route that involved two cyclobutane fragmentations. The first of these employed a retro-aldol cleavage to generate the α-pyridone ring of huperzine A, and the second invoked a novel intramolecular aza-Prins reaction in tandem with stereocontrolled scission of a cyclobutylcarbinyl cation to create the aminobicyclo[3.3.1]nonene framework of the natural alkaloid.",10.1021/ol400012s,2013-01-24,0.6085328871641025
Tetrahedron,Short and efficient synthesis of (R)-4-Hydroxy-4-methyl cyclohexenone,,10.1016/0040-4039(95)00581-v,1995-05-01,0.6085280217534655
Journal of Organic Chemistry,"Hemisynthesis of 2,3,4-<sup>13</sup>C3-1,4-Androstadien-3,17-dione: A Key Precursor for the Synthesis of <sup>13</sup>C3-Androstanes and <sup>13</sup>C3-Estranes","In this contribution, we describe two simple and efficient routes for the preparation of keto-aldehyde 1, a key intermediate for the synthesis of 13 C3-androstanes and 13 C3-estranes. In the first route, the targeted aldehyde 1 was obtained in 40% overall yield from 1,4-androstadien-3,17-dione (3 mmol scale) via a two-step sequence involving a one-pot, abnormal ozonolysis/sulfur oxidation/retro-Michael/ozonolysis process. Alternatively, a second route from 4-androsten-3,17-dione, using a six-step sequence, was optimized to produce 40 mmol batches of the key intermediate 1 in 42% overall yield. At the final stage, the A-ring was reconstructed through a Wittig reaction with the 1-triphenylphosphoranylidene- 13 C3-2-propanone 2, followed by an intramolecular condensation assisted by thioacetic acid via a Michael addition/retro-Michael reaction sequence to provide 2,3,4- 13 C3-1,4-androstadien-3,17-dione.",10.1021/acs.joc.7b03216,2018-03-01,0.6085236947866807
Tetrahedron,"A new process to prepare 3,6-dichloro-2-hydroxybenzoic acid, the penultimate intermediate in the synthesis of herbicide dicamba",,10.1016/j.tetlet.2019.03.024,2019-03-09,0.6085189975549402
Organic Letters,Total Synthesis of (+)-Brefeldin A,"(+)-Brefeldin A was synthesized through an efficient route, which features (1) construction of the five-membered ring from a Crimmins aldol via tandem Li-I exchange and carbanion-mediated cyclization with concurrent removal of the chiral auxiliary, (2) introduction of the lower side chain (C10 to C16) via a Rh-catalyzed Michael addition of a vinyl boronic acid, (3) stereoselective reduction of the C7 ketone with SmI2, and (4) a 2-methyl-6-nitrobenzoic anhydride-mediated (Shiina) lactonization.",10.1021/ol800137f,2008-03-14,0.608514514107282
Journal of Organic Chemistry,Biomimetic Total Synthesis of (±)-Doitunggarcinone A and (+)-Garcibracteatone,"A full account of our oxidative radical cyclization approach to the synthesis of garcibracteatone and doitunggarcinone A is presented. This includes the first enantioselective synthesis of garcibracteatone, which allowed the absolute configuration of the natural compound to be determined. The first synthesis of doitunggarcinone A is also described, which confirms our reassignment of the relative configuration of this molecule. Novel syntheses of monoterpene fragments used to construct the target molecules are also reported.",10.1021/jo500027k,2014-02-27,0.6085136003577544
Organic Letters,Total Synthesis of (−)-Polycavernoside A: Suzuki–Miyaura Coupling Approach,"A total synthesis of (-)-polycavernoside A, a marine lethal toxin isolated from the edible alga Gracilaria edulis , has been achieved via a convergent approach. The synthesis is highlighted by catalytic asymmetric syntheses of the two key fragments and their union through Suzuki-Miyaura coupling and Keck macrolactonization.",10.1021/ol301278e,2012-06-06,0.6085125210394453
Synthesis,"Synthesis of Thiophene-Type S,S- and N,S-Ligands Derived from (+)-Nopinone","The new chiral thiophene 3 was prepared from (+)-nopinone via a de novo construction of the thiophene nucleus. From compound 3 four new S,S- and N,S-ligands, namely the C 1-symmetric 2-(thiophen-2-yl)pyridine 7 and the C 2-symmetric 2,2′-bithiophene 5, 2,6-di(thiophen-2-yl)pyridine 8, and 2,6-di(thiophen-2-yl)thiophene 9 were synthesized.",10.1055/s-0030-1260079,2011-06-21,0.6085102641120901
Organic Process Research & Development,"Practical, Scalable, Enantioselective Synthesis of (2<i>R</i>,3<i>R</i>)-<i>N</i>-Boc-2-amino-3- cyclohexyl-3-hydroxypropanoic Acid","An enantioselective synthesis of (2 R,3 R )-2-( tert -butoxycarbonyl)amino-3-cyclohexyl-3-hydroxypropanoic acid has been described starting from enantiomerically enriched ethyl 3-cyclohexyl-2,3-dihydroxypropanoate, easily available by Sharpless asymmetric dihydroxylation. The key reaction is the direct preparation of a sulfate by diol treatment with sulfuryl chloride, thus avoiding ruthenium-catalyzed sulfite oxidation.",10.1021/op050076l,2005-07-23,0.6085011037994731
Synlett,Synthesis of β-TrifluoromethylatedEnones: An Unexpected Reactivity of Trifluoromethylated WeinrebEnamides towards Organolithium Species,β-Trifluoromethylated enones can be synthesized in four steps from ethyl trifluoroacetoacetate. The key intermediate is a weinreb β-trifluoromethylated enamide.,10.1055/s-0029-1216748,2009-05-07,0.6084974313122136
Journal of Organic Chemistry,Diastereoselective Synthesis of Bridged Polycyclic Alkaloids via Tandem Acylation/Intramolecular Diels–Alder Reaction,"A mild and efficient stereoselective synthesis of hexacyclic indole alkaloids with a tetrahydro-β-carboline motif has been developed by utilizing the Pictet-Spengler reaction and tandem N-acylation followed by intramolecular Diels-Alder cyclization. Initially, a diene unit was installed in the tetrahedron β-carboline skeleton through Pictet-Spengler cyclization of the corresponding aldehyde with tryptophan ester. The dienophile moiety was introduced by N-acylation of tetrahydro-β-carboline. Successive, in situ, [4 + 2] intramolecular Diels-Alder cycloaddition of the activated dienophile and conjugated diene containing intermediate furnished bridged polycyclic heterocycles with high diastereoselectivity. Formation of four new rings, five new covalent bonds, and five new chiral centers with excellent stereoselectivity is the key feature of this strategy. The diastereoselective formation of product was attributed to intramolecular chirality transfer through a chiral amino acid. The stereoselective outcome of this tandem reaction was confirmed by X-ray crystallographic studies. The developed synthetic strategy was also explored on a soluble polymer support to incorporate the advantage of rapid synthesis and a high-throughput workup process toward the development of a green synthetic protocol for polycyclic alkaloids.",10.1021/jo401364s,2013-09-05,0.6084961198047971
Journal of the American Chemical Society,Development of an Enantiodivergent Strategy for the Total Synthesis of (+)- and (−)-Dragmacidin F from a Single Enantiomer of Quinic Acid,"An enantiodivergent strategy for the total chemical synthesis of both (+)- and (-)-dragmacidin F beginning from a single enantiomer of quinic acid has been developed and successfully implemented. Although unique, the synthetic routes to these antipodes share a number of key features, including novel reductive isomerization reactions, Pd(II)-mediated oxidative carbocyclization reactions, halogen-selective Suzuki couplings, and high-yielding late-stage Neber rearrangements.",10.1021/ja050586v,2005-04-01,0.6084935721402153
Tetrahedron,"Transformation of protoberberines into benzo[C]phenanthridines a novel and efficient synthesis of antitumor benzo[C]phenanthridine alkaloids, fagaronine and nitidine",,10.1016/s0040-4039(01)81554-9,1984-01-01,0.6084856503380908
Journal of Organic Chemistry,"First Total Synthesis of Aspinolide B, a New Pentaketide Produced by <i>Aspergillus </i><i>o</i><i>chraceus</i>","The first asymmetric total synthesis of Aspinolide B (1), a new 10-membered lactone discovered by chemical screening methods in the cultures of Aspergillus ochraceus, has been accomplished. The key steps included a selective Felkin-type addition of TMS-acetylene to aldehyde 3a and a Nozaki-Hiyama-Kishi coupling reaction to build the required 10-membered ring. This synthesis confirmed the absolute stereochemistry of aspinolide B, established through Helmchen's method and corrected its previously reported specific optical rotation.",10.1021/jo000327i,2000-08-18,0.6084785241541768
Tetrahedron,"Efficient synthesis of the 2-amino-6-chloro-4-cyclopropyl-7-fluoro-5-methoxy-pyrido[1,2-c]pyrimidine-1,3-dione core ring system",,10.1016/j.tetlet.2008.11.121,2008-12-07,0.6084741818589521
Organic Letters,Enantioselective Total Syntheses of Pygmaeocins B and C,The first enantioselective total syntheses of pygmaeocins B and C have been accomplished using an efficient and highly diastereoselective intramolecular Heck cyclization for the construction of a quaternary stereogenic center and the functionalized A-ring of the natural products as the key step.,10.1021/ol401543b,2013-06-28,0.6084539757772913
Tetrahedron,Stereoselective synthesis of polyenic alcohols. A new route to the leukotrienes B.,,10.1016/s0040-4039(00)85346-0,1986-01-01,0.6084538589125493
Synlett,"A Concise Formal Synthesis of Unnatural (+)-Aphanorphine from (2<i>S</i>,4<i>R</i>)-4-Hydroxyproline","(-)-Aphanorphine methyl ether was synthesized in ten steps from commercially available (2S,4R)-4-hydroxyproline, ­featuring the C-2 configuration inversion of an intermediate amide and intramolecular Friedel-Crafts reaction. The present work ­constitutes a formal synthesis of unnatural (+)-aphanorphine.",10.1055/s-2006-956499,2006-12-20,0.6084485300955573
European Journal of Organic Chemistry,Total Synthesis of Plagiochin D by an Intramolecular S<sub>N</sub>Ar Reaction,"Abstract The total synthesis of plagiochin D, a macrocyclic bis(bibenzyl) compound isolated from the liverwort plagiochila acanthophylla , has been accomplished. Closure of the key 16‐membered ring, which contained biphenyl ether and biaryl units, was achieved in good yield by an intramolecular S N Ar reaction. The Suzuki and Wittig protocols proved to be powerful tools for the construction of a linear precursor that was crucial for ring cyclization.",10.1002/ejoc.201001412,2011-04-21,0.6084461206372117
Tetrahedron,"1,6-dihydro-3(2H)-pyridinones as synthetic intermediates. Total synthesis of (±)-tecomanine",,10.1016/s0040-4039(01)92518-3,1981-01-01,0.6084361970698768
Journal of the American Chemical Society,Total Synthesis of (−)-Heptemerone B and (−)-Guanacastepene E,"A concise, stereoselective, and convergent total synthesis of the unnatural enantiomer of the neodolastane diterpenoid heptemerone B has been completed. Saponification of (-)-heptemerone afforded (-)-guanacastepene E. The absolute stereochemistry of (-)-heptemerone B was thus established as 5-(S), the same as (-)-guanacastepene E. The longest linear sequence of the synthesis comprises 17 (18) steps from simple known starting materials. Our general synthetic approach integrates a diverse set of reactions, including an intramolecular Heck reaction to create one quaternary stereocenter and a cuprate conjugate addition for the establishment of the other. The central seven-membered ring was closed with an uncommon electrochemical oxidation, whereas the five-membered ring was formed through ring-closing metathesis. The absolute configuration of the two key building blocks was established through an asymmetric reduction and an asymmetric ene reaction.",10.1021/ja0660507,2006-12-01,0.6084340539097763
Organic Letters,Efficient Chemoenzymatic Synthesis of Pelitrexol via Enzymic Differentiation of a Remote Stereocenter,"[structure: see text] An efficient chemoenzymatic process is described for the synthesis of pelitrexol, a novel GARFT inhibitor. The remoteness of this molecule's stereocenter in the tetrahydropterin moiety from the terminal carbonyl group provided a significant challenge in synthesis. The introduction of an oxalamic ester adjacent to the stereocenter dramatically enhanced an enzyme's enantioselectivity for hydrolysis at the terminal ester, producing the desired S-acid with high optical purity and yield. The recycling of the ""wrong"" enantiomer is achieved via a dehydrogenation/hydrogenation strategy.",10.1021/ol0602755,2006-03-25,0.608429933602963
Synlett,A Two-Step Preparation of a New C<sub>4</sub> Chiral Building Block Derivative of D-Erythronic Acid,"All articles of this category 1,2;3,4-Di- O -isopropylidene-D-erythronic acid (2,2,2′,2′-Tetramethyl-[R,R-(4,4′-bi-1,3-dioxolan)]-5-one 4 , a new C 4 chiral building block derivative of D-erythronic acid was prepared in two steps from D-glucono- δ -lactone. erythronolactone - oxidation - gluconolactone - chiral building block - erythronamide",10.1055/s-1998-1972,1998-12-01,0.6084295108336585
Journal of Organic Chemistry,Development of the Synthesis of Desepoxy-Tedanolide C,"We are presenting the development of our route for the total synthesis of desepoxy-tedanolide C. Through the obtained analytical data, the proposed structure of tedanolide C is questioned and a different configuration for this natural product is proposed. Key steps of the synthesis are a Kiyooka aldol reaction that builds up the tertiary alcohol flanked by three oxygenated carbon atoms and two aldol reactions used for fragment couplings. A Julia-Kocienski olefination was used for installation of the side chain. Besides the successful synthesis, the development for the protecting group setup of the southwestern hemisphere is described in detail as well as another retrosynthetic attempt for building up the target molecule.",10.1021/acs.joc.3c02437,2024-01-25,0.6084259712160519
Tetrahedron,"A convergent, scalable and stereoselective synthesis of azole CYP51 inhibitors",,10.1016/j.tetlet.2017.09.070,2017-09-25,0.6084254937165692
Angewandte Chemie International Edition,Total Synthesis of (±)‐Gephyrotoxin by Amide‐Selective Reductive Nucleophilic Addition,"A chemoselective approach for the total synthesis of (±)-gephyrotoxin has been developed. The key to success was the utilization of N-methoxyamides, which enabled the direct coupling of the amide with an aldehyde and selective reductive nucleophilic addition to the amide in the presence of a variety of sensitive and electrophilic functional groups, such as a methyl ester. This chemoselective approach minimized the use of protecting-group manipulations and redox reactions, which resulted in the most concise and efficient total synthesis of (±)-gephyrotoxin described to date.",10.1002/anie.201308905,2013-11-29,0.608420274793019
Organic Letters,Total Synthesis of Iejimalide B. An Application of the Shiina Macrolactonization,"The potent anticancer compound iejimalide B (1) was prepared by a total synthesis through a strategy that features Julia olefinations, Wittig olefinations, a Carreira enantioselective alkynylation, a Heck reaction, a Marshall propargylation reaction, a Stille coupling, and a Shiina macrolactonization.",10.1021/ol702129w,2007-10-01,0.6084093894070314
Synlett,Synthesis of Useful Functionalized Prenyl Derivatives in the<i>E</i>or<i>Z</i>Configuration,"All articles of this category A stereospecific route to the E and Z isomers of 3-(1,3-dithian-2-yl)-2-methylpropenal from ethyl ( E )-3-methyl-4-oxo-2-butenoate and 2-dimethylhydrazonoacetaldehyde, respectively, is described.",10.1055/s-1991-20879,1991-01-01,0.6084043306968471
Organic Letters,Total Syntheses of Echinopines,"A concise and scalable synthesis of a cis-fused bicyclo[5.3.0]decane ring system has been developed for the total synthesis of echinopines. The core of the natural products was constructed efficiently through an intramolecular 1,3-dipolar cycloaddition and ring contraction strategy.",10.1021/ol400645v,2013-03-29,0.6083986224613548
Tetrahedron,Development of a synthetic route towards milbemycin β1: Preparation of an advanced model system.,,10.1016/s0040-4039(00)96835-7,1987-01-01,0.6083962336166943
Tetrahedron,Intramolecular [3+4] allyl cation cycloaddition: Novel route to hydroazulenes,,10.1016/s0040-4039(00)82267-4,1988-01-01,0.6083938237785724
Tetrahedron,"Generation of novel, potent urotensin-II receptor antagonists by alkylation–cyclization of isoindolinone C3-carbanions",,10.1016/j.tetlet.2009.06.025,2009-06-10,0.6083912754940087
Organic Letters,One-Pot Synthesis of Substituted Tetrahydrocyclobuta[<i>a</i>]naphthalenes by Domino Aldol Condensation/Olefin Migration/Electrocyclization,"A facile one-pot synthetic route for preparing the novel benzofused tricyclic skeleton of 1,2,2a,8b-tetrahydrocyclobuta[a]naphthalenes 5 is developed. The route was realized by a NaH-mediated tandem aldol condensation/olefin migration/electrocyclization of o-allylbenzaldehydes 1 with cinnamyl sulfones 3 in good yields.",10.1021/ol401152w,2013-05-22,0.6083884595637924
European Journal of Organic Chemistry,Inversion of Configuration of (S)-β-Hydroxy-γ-butyrolactone with Total Retention of the Enantiomeric Purity,"In this paper we report the inversion of configuration of (S)-β-hydroxy-γ-butyrolactone [(S)-1] to its (R) enantiomer (R)-1, with total retention of the enantiomeric purity, by a four-step procedure. The (R)-β-hydroxy-γ-butyrolactone [(R)-1] was thus synthetized with an overall chemical yield of 47% and > 97% ee. This transformation opens an economic route to the production of (R)-GABOB and (R)-carnitine, among other biologically active compounds, from a D-hexose source, or, alternatively, from the industrial waste compound (S)-carnitine. During the reaction sequence, the intermediate β-lactone 4 is also prepared, which is now under investigation as a chiral synthon for new synthetic applications.",10.1002/(sici)1099-0690(199911)1999:11<2705::aid-ejoc2705>3.0.co;2-4,1999-11-01,0.6083869312473539
European Journal of Organic Chemistry,Inversion of Configuration of (S)--Hydroxy--butyrolactone with Total Retention of the Enantiomeric Purity,"In this paper we report the inversion of configuration of (S)-β-hydroxy-γ-butyrolactone [(S)-1] to its (R) enantiomer (R)-1, with total retention of the enantiomeric purity, by a four-step procedure. The (R)-β-hydroxy-γ-butyrolactone [(R)-1] was thus synthetized with an overall chemical yield of 47% and > 97% ee. This transformation opens an economic route to the production of (R)-GABOB and (R)-carnitine, among other biologically active compounds, from a D-hexose source, or, alternatively, from the industrial waste compound (S)-carnitine. During the reaction sequence, the intermediate β-lactone 4 is also prepared, which is now under investigation as a chiral synthon for new synthetic applications.",10.1002/(sici)1099-0690(199911)1999:11<2705::aid-ejoc2705>3.3.co;2-w,1999-11-01,0.6083869312473539
Tetrahedron,A new synthetic route of corey lactone having ω-side chain,,10.1016/s0040-4039(00)73891-3,1993-08-01,0.6083862898418252
Organic Letters,"Synthesis of Conformationally Constrained 5,6,7,8-Tetrahydroimidazo[1,5-<i>a</i>]pyridine Inhibitors of Farnesyltransferase","[reaction: see text] Synthesis of the 8-amino-5,6,7,8-tetrahydroimidazo[1,5-a]pyridine ring system was accomplished by intramolecular cyclization of an iminium ion, derived from condensation of an amine and a substituted gamma-(1-imidazolyl)butyraldehyde. The reaction was used to produce conformationally restricted farnesyltransferase inhibitor analogues which exhibit improved in vivo metabolic stability.",10.1021/ol0002424,2000-10-10,0.6083714990107512
Synlett,"Convergent Approach to Nonsymmetrical 2,5-Diester Pyrroles","A convergent approach towards nonsymmetrical 2,5-diester pyrroles is described. The building blocks can be easily assembled in less than four steps allowing for facile construction of diversity. The synthesis uses a rhodium-catalyzed NH insertion, followed by a one-pot deprotection-condensation to yield the desired pyrroles.",10.1055/s-0030-1259074,2010-11-25,0.6083692061681586
Tetrahedron,"Synthesis and preliminary evaluation of 18F-labeled 1-(6,7-dimethyl-4-(methylamino)-1,3-dihydro-2H-pyrrolo[3,4-c]pyridin-2-yl)-2-(trans-2-(6-fluoropyridin-3-yl)cyclopropyl)ethan-1-one for imaging muscarinic acetylcholine receptor subtype 4",,10.1016/j.tetlet.2020.152060,2020-05-22,0.6083682094761775
Synthesis,Domino o-Alkylation and Heteroarylation of Iodoarenes: One-Pot Synthesis of Benzocyclohepta[b]indoles,A new strategy for the synthesis of benzocyclohepta[ b ]indoles via a palladium-catalyzed/norbornene-mediated domino intermolecular alkylation/intramolecular heteroarylation of iodoarenes is devised. This approach provides a straightforward route to polycyclic nitrogen-containing heterocycles with fused seven­-membered rings from readily accessible precursors.,10.1055/s-0032-1316876,2013-03-20,0.6083636077553927
Organic Letters,Stereocontrolled Total Synthesis of Potent Immunosuppressant FR901483,A total synthesis of the potent immunosuppressant FR901483 (1) has been accomplished. The key feature of our convergent synthesis is the stereoselective incorporation of the p-methoxybenzyl and methylamino groups within the core moiety 10. Tricycle 10 was itself constructed by an intramolecular aldol reaction of the symmetrical keto-aldehyde 7. [Structure: see text],10.1021/ol049074w,2004-07-10,0.6083614985327792
European Journal of Organic Chemistry,Asymmetric Formal Synthesis of (+)‐Lactacystin,"Abstract A formal synthesis of (+)‐lactacystin was achieved from commercially available isobutyraldehyde and ethyl acrylate. A Baylis–Hillman reaction, an intermolecular nucleophilic displacement under Mitsunobu conditions, a Sharpless asymmetric epoxidation, a palladium(0)‐catalyzed syn ‐selective ring opening of an epoxide by treatment with an azide, a one‐pot azide reductive lactamization, and a ruthenium‐catayzed oxidation were employed as the key steps.",10.1002/ejoc.201402700,2014-08-15,0.6083455785884284
Tetrahedron,A route to selective functionalization of polyhydroxypyrrolidines,,10.1016/j.tetlet.2011.12.037,2011-12-16,0.6083426427095386
Tetrahedron,An efficient synthesis of 5-hydroxy-4-oxo-L-norvaline from L-aspartic acid,,10.1016/s0040-4039(00)73803-2,1993-09-01,0.608338435874284
Journal of Organic Chemistry,Novel Synthesis of Highly Functionalized 14-β-Hydroxysteroids Related to Batrachotoxin and Ouabain,"The use of anionic polycyclization was investigated in an effort to develop a versatile and convergent synthesis of advanced tetracyclic intermediates of batrachotoxin and ouabain analogues. Two new 5-(trialkylsilyl)-2-cyclohexenones as A ring precursors and a new Nazarov intermediate (D ring precursor) were prepared for this purpose. The reaction of the unsaturated beta-keto aldehyde A ring precursor with the enolate of the Nazarov intermediate afforded, after subsequent transformations, a 14-beta-hydroxysteroid with complete control of stereochemistry.",10.1021/jo0355606,2004-01-10,0.6083328527826174
Journal of Organic Chemistry,De Novo Synthesis of (+)-Isofregenedol,An efficient enantioselective synthesis of (+)-isofregenedol was achieved in 13 steps from commercially available cyclohexene oxide without the use of protecting groups. The tetrahydronaphthalenic core of isofregenedol was obtained via a gold(I)-catalyzed benzannulation recently developed in our laboratory.,10.1021/jo801365z,2008-08-13,0.6083294349999803
Journal of the American Chemical Society,Biogenetically Inspired Approach to the <i>Strychnos </i>Alkaloids. Concise Syntheses of (±)-Akuammicine and (±)-Strychnine,"A linear synthesis of the indole alkaloid (+/-)-akuammicine (2) was completed by a novel sequence of reactions requiring only 10 steps from commercially available starting materials. The approach features a tandem vinylogous Mannich addition and an intramolecular hetero Diels-Alder reaction to rapidly assemble the pentacyclic heteroyohimboid derivative 8 from the readily available hydrocarboline 6. Oxidation of the E ring of 8 gave the lactone 9 that was converted into deformylgeissoschizine (11). The subsequent elaboration of 11 into 2 was effected by a biomimetically patterned transformation that involved sequential oxidation and base-induced skeletal reorganization. A variation of these tactics was then applied to the synthesis of the C(18) hydroxylated akuammicine derivative 36. Because 36 had previously been converted into strychnine (1) in four steps, its preparation constitutes a concise, formal synthesis of this complex alkaloid.",10.1021/ja010935v,2001-07-31,0.608325988344685
Journal of the American Chemical Society,Enantioselective Synthesis of the Bromopyrrole Alkaloids Manzacidin A and C by Stereospecific C−H Bond Oxidation,"The manzacidins represent a small family of structurally unique secondary metabolites found only sparingly in nature. Efforts to probe the pharmacological profile of these intriguing bromopyrrole alkaloids have been precluded by a deficiency of available material. Access to substantive quantities of both manzacidins A and C is now made possible through a rapid, enantioselective, and highly efficient synthesis that is described herein. The path to these targets showcases for the first time the distinct power of our catalytic C-H bond amination methodology for simplifying problems in alkaloid total synthesis. Application of this chemistry enables the facile and enantiospecific installation of tetrasubstituted carbinolamine stereocenters, functionality common to all of the manzacidins. The requisite materials for implementing our plan are assembled using modern tools for catalytic asymmetric synthesis that include both carbonyl-ene and directed hydrogenation reactions. In addition, a new protocol for tetrahydropyrimidine synthesis is established. The synthesis of each manzacidin comprises a 10-step sequence that proceeds in an overall yield of approximately 30%.",10.1021/ja028139s,2002-10-12,0.6083178661407321
Organic Process Research & Development,"Enantioselective Synthesis of Brinzolamide (AL-4862), a New Topical Carbonic Anhydrase Inhibitor. The “DCAT Route” to Thiophenesulfonamides","A large scale synthesis of the topical carbonic anhydrase inhibitors AL-4623A ( 13a ·HCl) and AL-4862 ( 13b ) from 3-acetyl-2,5-dichlorothiophene (“DCAT”, 1 ) is described. Reaction of 1 with NaSBn gave thioether 2, which was converted via sulfenyl chloride 3 and sulfenamide 5 to sulfonamide 6 . Bromination of 6 gave bromo ketone 7, which upon reduction with (+)-B-chlorodiisopinocampheylborane and cyclization of the resulting bromohydrin produced S thieno[3,2- e ]-1,2-thiazine 8a (96% ee) after chromatography. Treatment of 8a in THF with n -BuLi at −70 °C resulted in Li−Cl exchange. Reaction of the thienyllithium with SO 2 and hydroxylamine O-sulfonic acid afforded bis-sulfonamide 11a . Protection of 11a as the acetimidate 12a, followed by tosylation and amination, gave R amine 13a . The synthesis of 13b proceeded via primary sulfonamide 16, which was brominated, reduced, and cyclized to give S thieno[3,2- e ]-1,2-thiazine 18 (>98% ee). By virtue of the ionizable NH, 18 was separable from reduction byproducts by base extraction. Alkylation of 18 with 3-bromopropyl methyl ether afforded 8b, which was converted as above, via 11b, to AL-4862 ( 13b ). These procedures provided multihundred gram lots of 13a and 13b .",10.1021/op9802125,1999-02-18,0.6083142876807226
Organic Letters,Total Synthesis of Nannocystin A,"Nannocystin A is a 21-membered cyclodepsipeptide showing remarkable anticancer properties. Described is the total synthesis of nannocystin A, which features an asymmetric vinylogous Mukaiyama aldol reaction for efficient assembly of the penultimate open-chain precursor and a pivotal intramolecular Heck cross-coupling for the final macrocyclization.",10.1021/acs.orglett.6b02729,2016-10-13,0.6083092792034205
Tetrahedron,"Regioselective synthesis of novel 4-aryl-2-ethylthio-7-methyl pyrazolo[1,5-a]-[1,3,5]-triazines",,10.1016/j.tetlet.2006.05.168,2006-06-19,0.608301329632815
Tetrahedron,A flexible route to substituted hydroxy-cyclopentanones from cyclobutanones,,10.1016/j.tetlet.2015.04.063,2015-04-25,0.6082943261957365
Tetrahedron,"Improved synthesis of 7,12-dimethylbenz[a]anthracene",,10.1016/s0040-4039(01)83681-9,1977-01-01,0.6082936113601074
Synthesis,A New Enantioselective Catalytic Route to Florhydral<sup>®</sup>,"The valuable fragrance Florhydral® [3-(3-isopropylphenyl)butanal] has been synthesized in almost enantiomerically pure form by a new catalytic route. The key step of the process is the enantioselective hydrogenation of (E)-3-(3-isopropylphenyl)but-2-en-1-ol, which is carried out with asymmetric inductions of up to 97% using an iridium-phosphinooxazoline chiral catalyst.",10.1055/s-2008-1067167,2008-07-09,0.6082820480821728
Synthesis,An Improved and Convenient New Synthesis of the Pheromone Components of the Tomato Leafminer Tuta absoluta,"A convenient new synthesis of the two pheromone components of the tomato pest Tuta absoluta in high overall yields and high stereoselectivity (30% yield, E , Z , Z 97% for the major compound and 23% yield, E , Z 99% for the minor component) is reported. The approaches compare favorably with others previously described.",10.1055/s-0034-1379977,2015-01-15,0.6082774132880063
Organic Letters,Studies Directed toward the Synthesis of Hamigeran B: A Catalytic Oxidative Cyclization,An approach to the synthesis of hamigeran B is described. Key steps include a Tius-Nazarov cyclization and a palladium-catalyzed oxidative cyclization of an α-hydroxyenone.,10.1021/ol102478h,2010-11-16,0.6082771258791
Tetrahedron,A convergent scheme for the synthesis of spiroketals and the synthesis of (±)-chalcogran,,10.1016/s0040-4039(00)92727-8,1980-01-01,0.6082740420855774
Journal of the American Chemical Society,Total Synthesis of Alkaloid (±)-G. B. 13 Using a Rh(I)-Catalyzed Ketone Hydroarylation and Late-Stage Pyridine Reduction,"Total synthesis of the Galbulimima alkaloid G. B. 13 was achieved utilizing a functionalized pyridine moiety as a piperidine surrogate. Key to the success of the synthesis was the development of an unprecedented rhodium-catalyzed 1,2-addition of an arylboronic ester into an unactivated ketone.",10.1021/ja9063487,2009-09-01,0.6082700259568458
Synthesis,An Improved Synthesis of<i>trans</i>-Zeatin,,10.1055/s-1972-21954,1972-01-01,0.6082619781134033
Synthesis,"An Improved Synthesis of 5,6-<i>trans</i>-Ergocalciferol",,10.1055/s-1978-24871,1978-01-01,0.6082619781134033
Angewandte Chemie International Edition,Cooperative Brønsted Acid and Photo‐Promoted Stereoselective Synthesis of Substituted Piperidones,"Saturated nitrogen heterocycles are highly prevalent in medicinal chemistry, agrochemistry, and material science. Despite extensive research to access substituted piperidines and related compounds, there remains a strong demand for new stereoselective approaches. We present a Brønsted acid-promoted, light-induced formal ring-insertion strategy for the efficient synthesis of piperidone and pyrrolidone derivatives. This method enables the efficient construction of thermodynamically disfavored cis-disubstituted piperidone and pyrrolidone derivatives. A key aspect of this strategy is the use of an acyl imidazole as a uniquely capable chromophore activator, in cooperation with the Brønsted acid, which controls both reactivity and stereoselectivity without the need for photosensitizers. The unique properties of the in situ generated carbonyl triplet diradical enable a selective 1,5-hydrogen atom transfer process, followed by C─N bond cleavage and a subsequent Mannich reaction, offering broad functional group tolerance. The synthetic utility of this methodology was exemplified by the preparation of key intermediates for the synthesis of neurokinin 1 antagonist drug candidates.",10.1002/anie.202516050,2025-11-02,0.6082611693161013
Angewandte Chemie International Edition,Efficient Access to Oseltamivir Phosphate (Tamiflu) via the <i>O‐</i>Trimesylate of Shikimic Acid Ethyl Ester,The same azide intermediate as that used in the current technical synthesis of Tamiflu can be prepared in only eight steps and with only three workups; protecting group manipulations and chromatographic purification are not required. This approach includes a new protocol for aziridine formation to avoid competitive aromatization.,10.1002/anie.200901561,2009-06-29,0.6082546021232804
Organic Letters,Total Synthesis of (+)-<i>trans</i>-Dihydronarciclasine Utilizing Asymmetric Conjugate Addition,A highly efficient short-step construction of the common phenanthridine skeleton of pancratistatin-class alkaloids was accomplished in enantiomerically pure form using chiral ligand-controlled asymmetric conjugate addition. The utility of the intermediate was demonstrated by the total synthesis of (+)-trans-dihydronarciclasine with mild oxidation from an amine to an amide as a key step.,10.1021/ol302757y,2012-11-12,0.6082464136515099
European Journal of Organic Chemistry,Synthesis and Characterization of Azine‐[5]Helicene Hybrids,"Novel azine‐helicene hybrids (pyridine‐, pyrazine‐ and quinoxaline‐fused along the central ring [5]helicenes) have been prepared in good overall yields through a five‐step synthetic sequence. Commercially available 2,3‐dihaloazines were used as starting materials. To discern the effect of merging an azine moiety within a helical skeleton, the X‐ray structures, UV/Vis absorption spectra, cathodic and anodic electrochemistry of the helicene hybrids were investigated and compared to that of the parent [5]helicene.",10.1002/ejoc.201900818,2019-07-12,0.6082216838341346
Synlett,"Synthesis and Selective Functionalization of [1,2,4]Triazolo-[4,3-a]pyrazines","A new tactic for the synthesis and selective functionalization of [1,2,4]triazolo[4,3- a ]pyrazines has been developed using an oxidative cyclization as key step. Furthermore, novel strategies for introducing diverse substituents in all positions of the heterocycle were identified.",10.1055/s-0034-1378946,2015-01-08,0.608218829717928
Organic Letters,Synthesis of Rigid Homo- and Heteroditopic Nucleobase-Terminated Molecules Incorporating Adenine and/or Thymine,"A series of homo- and heteroditopic thymine- and/or adenine-terminated molecules incorporating rigid aryl or oligo(phenylene ethynylene) linkers has been efficiently synthesized. The key steps involved in the synthesis are the construction of the N-arylated nucleobases using the Chan-Lam-Evans-modified Ullman coupling and their further elaboration using the Sonogashira coupling. Furthermore, the synthesis of a rigid tripodal thymine derivative is reported.",10.1021/ol071006x,2007-06-29,0.6082164868121219
Synthesis,"Asymmetric Synthesis of<i>threo</i>-(2<i>S</i>,3<i>R</i>)-2-Amino-3-hydroxypentanedioic Acid 5-Amide (<i>threo</i>-β-Hydroxy-L-glutamine)","All articles of this category A new method for the synthesis of threo -ß-hydroxy-L-glutamine consists of epoxidation of ( S )-3-benzyloxycarbonyl-5-oxo-4-vinyltetrahydro-1, 3-oxazole (protected L-vinylglycine) and regioselective ring cleavage.",10.1055/s-1986-31863,1986-01-01,0.6082107304894614
Tetrahedron,Total synthesis of tautomycin: Efficient aldol coupling of two large subunits,,10.1016/s0040-4039(00)76974-7,1994-07-01,0.6082106966523656
Synthesis,"Synthesis of Unsymmetrically Substituted 6,12-Diaryldibenzo[<i>b,f</i>][1,5]diazocines and Their Precursor Schiff Bases","All articles of this category A new route for the preparation of some unsymmetrically substituted 6, 12-diaryldibenzo[ b,f ][1,5]diazocines 5 and their precursor Schiff bases 4 from 2-isocyanatobenzoyl chloride and its 5-chloro derivative are described.",10.1055/s-1986-31601,1986-01-01,0.6082042245468884
Tetrahedron,"Synthesis of a common advanced indane intermediate for the formal total synthesis of (±)-puraquinonic acid, (±)-deliquinone, and (±)-russujaponol",,10.1016/j.tetlet.2024.155078,2024-04-21,0.6082021292928379
Synlett,Synthesis of<i>trans</i>-(2-Aminocyclopropyl)alanine - A Key Constituent of the Novel Antitumor Antibiotic Belactosin A,"All articles of this category Racemic 3-( trans -2-aminocyclopropyl)alanine was prepared in its 3,3-dideuterio-labelled form 3b from tert -butyl 2,3-dibromopropanoate 4 and nitromethane through a nine-step sequence in 8% overall yield. The newly developed access to enantiomerically pure ( trans -2-nitrocyclopropyl)methanol ( S , S )- 6a also constitutes a formal synthesis of enantiomerically pure 3-( trans -2-aminocyclopropyl)alanine ( S , S , S )- 3a , a key intermediate for the total synthesis of the novel antitumor antibiotic belactosin A. amino acids - amino alcohols - antitumor agents - cyclopropanes - enantiomeric resolution",10.1055/s-2000-8679,2000-01-01,0.6081984581868627
Journal of Organic Chemistry,Copper(I)-Catalyzed Regioselective Amination of <i>N</i>-Aryl Imines Using TMSN<sub>3</sub> and TBHP: A Route to Substituted Benzimidazoles,"A novel and efficient copper-catalyzed amination of N-aryl imines is described. This one-pot, multicomponent reaction, in which imine acts as a directing group by chelating to the metal center, affords a potential route for the transformation of the commercial aryl amines, aldehydes, and azides into valuable benzimidazole structural units with wide substrate scope and diversity. The synthetic and mechanistic aspects are presented.",10.1021/jo502574u,2015-01-14,0.6081921802527079
Tetrahedron,"New synthesis of 5-amino-4-hydroxy-2,6-dimethylheptanoic acid, a hydroxyethylene isostere of the Val-Ala dipeptide",,10.1016/s0040-4039(00)01773-1,2000-12-01,0.6081502744395549
Synthesis,"A Facile and Practical Synthesis of Nicolaou's Key Intermediates, 2-Methyl- and 2,6-Dimethyltetrahydropyrans, toward the Total Synthesis of Ladder-Shaped Polyethers","A facile and robust method to prepare 2-methyl- and 2,6-dimethyltetrahydropyrans, most useful Nicolaou intermediates for the synthesis of ladder-shaped polyethers, is disclosed. The established highly practical recipe, adopting chemo- and stereoselective catalytic oxidations and one-pot reactions with few chromatographic purifications, would significantly facilitate the large-scale supply of pivotal monocyclic building blocks, which is a rate-determining process of gigantic tetrahydropyran-containing natural products synthesis.",10.1055/s-0033-1338503,2013-07-19,0.6081489487457723
Journal of the American Chemical Society,An Enantioselective Total Synthesis and Stereochemical Revision of (+)-Citrinadin B,"This manuscript describes an enantioselective synthesis of the naturally occurring alkaloid citrinadin B. The synthetic effort revealed an anomaly in the original structural assignment that has led to the proposal of a stereochemical revision. This revision is consistent with the structures previously reported for a closely related family of alkaloids, PF1270A-C. The synthesis is convergent and employs a stereoselective intermolecular nitrone cyloaddition reaction as a key step.",10.1021/ja405548b,2013-07-09,0.6081456896395939
Journal of Organic Chemistry,Total Synthesis of the Microtubule Stabilizing Antitumor Agent Laulimalide and Some Nonnatural Analogues:  The Power of Sharpless' Asymmetric Epoxidation,"Three different routes are described for the synthesis of deoxylaulimalide (3), which is the immediate precursor of the marine sponge metabolite laulimalide (1). These routes mainly differ with respect to their ring closing step. Thus, route 1 uses a Still-Gennari olefination, route 2 a Yamaguchi lactonization, and route 3 an intramolecular allylsilane-aldehyde addition for establishing the macrocyclic structure. The unprotected deoxy derivative 3 was subjected to Sharpless' asymmetric epoxidation (SAE). With (R,R)-tartrate the 16,17-epoxide laulimalide (1) is formed selectively, whereas (S,S)-tartrate generates the 21,22-epoxide 142. This demonstrates the high reagent control involved in the SAE process, which in this case is used to achieve high stereo- and regioselectivity. Laulimalide and some derivatives thereof have been tested with respect to antitumor activity and compared to standard compounds paclitaxel and epothilone B.",10.1021/jo026743f,2003-03-25,0.6081372957537423
Journal of Organic Chemistry,Total Synthesis and Biological Evaluation of (−)-Apicularen A and Its Analogues,"The total synthesis of (-)-apicularen A (1), a highly cytostatic 12-membered macrolide, and its analogues is described. The convergent and distinct approach not only provides 1, but also opens the opportunity to synthesize C10-C11 functional analogues of 1. The key steps of the total synthesis include assembling of iodoalkene 12 and aldehyde 13by Nozaki-Hiyama-Kishi (NHK) coupling, stereospecific construction of 2,6-trans-disubstituted dihydropyran by Pd(II)-catalyzed 1,3-chirality transfer reaction, and Yamaguchi macrolactonization. The (17E,20Z,22Z)-heptadienoylenamine moiety in the side chain is installed by an efficient Cu(I)-mediated coupling to complete the synthesis. Analogues of C11-epi-, C11-deoxy-C10-α-hydroxy-, and C10-C11 dehydrated apicularen A 3-5 were also prepared. Cytostatic activities of (-)-apicularen A and the three analogues for three different cancer cell lines are described.",10.1021/jo2019762,2011-11-25,0.6081372670677676
Synlett,Total Synthesis of Asperchalasine A,"Here we briefly reviewed recent synthetic progress toward cytochalasan trimer, asperchalasine A by Tang, Trauner and our group. This process features a highly stereoselective intermolecular Diels–Alder reaction and a HWE or RCM macrocyclization to establish the key monomer aspochalasin B. A late-stage biomimetic oxidative dearomatization of triphenol and subsequent [5+2] cycloaddition cascade furnished asperchalasine A. We anticipate that this key reaction could also be used for the synthesis of other merocytochalasans, and provide some insight into the biosynthetic connections of merocytochalasans. 1 Introduction2 Total Synthesis of Aspochalasin B 3 Total Synthesis of Asperchalasine A 4 Conclusions",10.1055/s-0039-1691500,2019-12-13,0.6081186077414558
Tetrahedron,Angular alkylation through a novel intramolecular cationic cyclization reaction. A simple stereospecific route to polycyclic bridged-ring intermediates towards some complex diterpenoids,,10.1016/s0040-4039(01)94902-0,1978-01-01,0.6081158774528377
Journal of Organic Chemistry,Regiocontrol by Remote Substituents. A Direct Total Synthesis of Racemic Hongconin,"The total synthesis of hongconin (1) has been completed. Key steps include the metalation of a benzylic alcohol, the formation of a six-membered ring ether via a mercury-mediated cyclization, and the regioselective installation of the naphthalene ring by way of a Diels-Alder reaction.",10.1021/jo00087a044,1994-04-01,0.6081014114166039
Organic Letters,"Polyol Synthesis with β-Oxyanionic Alkyllithium Reagents: Syntheses of Aculeatins A, B, and D","Synthesis of ketone aldol products using a non-aldol route was developed. The beta-phenylthio alcohols were prepared from optically pure oxiranes. Deprotonation and reductive lithiation generated the key intermediate, a beta-oxyanionic alkyllithium reagent. Addition to a Weinreb amide produced the beta-hydroxy ketone in >90% yield using only 1.5 equiv of the phenylthio alcohol. Stereoselective reduction of the ketone led to either the syn- or anti-1,3-diol. This simple, convergent sequence was used to prepare aculeatins A, B, and D from a common intermediate.",10.1021/ol901623h,2009-08-19,0.6080931887948821
Angewandte Chemie International Edition,Total Synthesis of Clerodin,"Abstract The first and asymmetric total synthesis of clerodin, the earliest isolated clerodane diterpenoid, has been achieved by tail‐to‐head cyclization and modular synthetic strategies. The C19 oxidized trans ‐decalin core was constructed via a tail‐to‐head cyclization of an epoxide ene‐yne compound containing an internal oxygenated methyl‐bearing alkene. This process involved a titanium(III) catalyzed epoxide ring‐opening/ene‐yne cyclization. The furan fragment was assembled through a metallaphotoredox‐enabled deoxygenative coupling of an alcohol precursor. A SmI 2 ‐mediated elimination of a pre‐installed acetal established the 2,3‐dihydrofuran motif.",10.1002/anie.202515206,2025-10-06,0.6080890357936414
European Journal of Organic Chemistry,Diastereoselective Synthesis of the A‐B‐C Tricyclic Ring Structure of Stemocurtisine,Abstract The diastereoselective synthesis of the A‐B‐C tricyclic ring structure of the Stemona alkaloid stemocurtisine is described. This tricyclic precursor to the natural product was obtained in 19 steps from a known vinyl iodide. Attempts to prepare the C‐3a–C‐11 ether moiety of this alkaloid through a photochemically induced oxidative cyclization method were unsuccessful because of the cleavage of the A‐ring.,10.1002/ejoc.201501080,2015-11-09,0.6080865468572312
Journal of Organic Chemistry,Total Synthesis of Indole Alkaloid (±)-Subincanadine F via SmI<sub>2</sub>-Mediated Ring Opening and Bridge-Forming Mannich Reaction,"The first total synthesis of (+/-)-subincanadine F, a bioactive indole alkaloid structurally featuring a 1-azabicyclo[4.3.1]decane unit, has been realized from 1-(para-methoxybenzyl)tryptamine in six steps. The bridge-containing tetracyclic framework of subincanadine F was efficiently assembled by a SmI2-mediated ring opening followed by an acid-mediated Mannich reaction. In addition, the tetracyclic ketoester 6, a key intermediate potentially useful for synthesizing structurally related indole alkaloids as well, was obtained in one step from alpha,beta-diketoester 5.",10.1021/jo061724h,2006-11-14,0.608086513468184
Synlett,"New Synthesis of 2,3-Diarylxanthones","A new synthesis for 2,3-diarylxanthones is described. This was accomplished by aldol condensation of 3-bromo-2-methylchromone with benzaldehydes leading to the formation of 3-bromo-2-styrylchromones, followed by Heck reaction with styrenes.",10.1055/s-2005-921928,2005-01-01,0.6080836400038088
Organic Letters,A Convenient and Asymmetric Protocol for the Synthesis of Natural Products Containing Chiral Alkyl Chains via Zr-Catalyzed Asymmetric Carboalumination of Alkenes. Synthesis of Phytol and Vitamins E and K,"[reaction: see text]. A convenient and asymmetric protocol for the synthesis of chiral oligoisoprenoids is described. Typically, a C14 vitamin E side chain 5 was synthesized in 47% yield over four steps. Isomeric purity of 5 was upgraded to >99% R at C-2 and 97% R at C-6 by the statistical formation of stereoisomeric p-phenylenebisurethanes and their diastereomeric separation. In addition, phytol and vitamin K were synthesized in 21% and 28% overall yields, respectively, over five steps from 1.",10.1021/ol010142d,2001-09-27,0.6080825742401946
Journal of Organic Chemistry,"Synthesis of (+)-CP-99,994 via Pd(0)-Catalyzed Asymmetric Allylic and Homoallylic C−H Diamination of Terminal Olefin","This paper describes an asymmetric synthesis of the potent substance P receptor antagonist (+)-CP-99,994 from 4-phenyl-1-butene via Pd(0)-catalyzed asymmetric allylic and homoallylic C-H diamination.",10.1021/jo9015584,2009-09-01,0.6080778322610536
Journal of the American Chemical Society,Total Synthesis of (−)-Steganone Utilizing a Samarium(II) Iodide Promoted 8-Endo Ketyl−Olefin Cyclization,"A six-step synthesis of (±)-steganone from commercially available 3,4,5-trimethoxybenzyl alcohol features a samarium(II) iodide promoted 8-endo ketyl−olefin coupling to install, in a single transformation, the 8,5 ring system common to the lignan lactones. The racemic synthesis provided the basis for the construction of (−)-steganone, which exploited a chromium tricarbonyl moiety both to establish and protect the desired absolute stereochemistry through key transformations, including a SmI 2 -promoted 8-endo radical cyclization and two palladium-catalyzed couplings.",10.1021/ja9930059,1999-12-22,0.6080708602521568
Journal of Organic Chemistry,Total Synthesis of Pteridic Acids A and B,"The total synthesis of pteridic acids A and B is reported. The convergent asymmetric synthesis involved the use of a diastereoselective ethyl ketone aldol reaction followed by an efficient spiroketalization and provided pteridic acids A and B in 2.9% and 2.8% overall yield, respectively.",10.1021/jo9010365,2009-07-02,0.6080699750376233
Tetrahedron,"An improved synthesis of antheridic acid, the antheridium inducing factor from the fern anemia phyllitidis",,10.1016/0040-4039(88)85156-6,1988-01-01,0.6080671109520063
Tetrahedron,Synthesis and chemistry of new benzoporphyrins,,10.1016/s0040-4039(99)01825-0,1999-12-01,0.6080622333117669
Tetrahedron,"Chemistry of 3,4-epoxy-2-methylene oxolanes: A new synthesis of furanes and dihydrofuranes",,10.1016/0040-4039(96)00442-x,1996-04-01,0.6080622333117669
Journal of Organic Chemistry,Biocatalytic Organic Synthesis of Optically Pure (<i>S</i>)-Scoulerine and Berbine and Benzylisoquinoline Alkaloids,"A chemoenzymatic approach for the asymmetric total synthesis of the title compounds is described that employs an enantioselective oxidative C-C bond formation catalyzed by berberine bridge enzyme (BBE) in the asymmetric key step. This unique reaction yielded enantiomerically pure (R)-benzylisoquinoline derivatives and (S)-berbines such as the natural product (S)-scoulerine, a sedative and muscle relaxing agent. The racemic substrates rac-1 required for the biotransformation were prepared in 4-8 linear steps using either a Bischler-Napieralski cyclization or a C1-Cα alkylation approach. The chemoenzymatic synthesis was applied to the preparation of fourteen enantiomerically pure alkaloids, including the natural products (S)-scoulerine and (R)-reticuline, and gave overall yields of up to 20% over 5-9 linear steps.",10.1021/jo201056f,2011-07-08,0.6080589832884721
Organic Process Research & Development,An Efficient Synthesis of 2-Quinoxalinecarboxylic Acid,"Development of a cost efficient and scaleable process for 2-quinoxalinecarboxylic acid is described. The primarily goals of the development work were to improve the overall yield of the process, to minimize the use of environmentally unacceptable materials, and to obtain a material with a high level of purity. A variety of approaches were examined, and the most efficient method was a condensation of o -phenylenediamine with a monosaccharide followed by a mild peroxide oxidation.",10.1021/op049951d,2004-06-16,0.6080572624064001
European Journal of Organic Chemistry,Total Synthesis of the (+)‐Antimycin A Family,"Abstract An asymmetric aldol reaction using Oppolzer's sultam has provided a practical and efficient synthetic route (15 steps, overall yield ca. 24 %) to 12 compounds of the Antimycin A family and deisovalerylblastmycin, which were obtained in pure form on a 60–300 mg scale. In the syntheses, the nine‐membered dilactone ring was constructed successfully by lactonization of a 2‐pyridinethiol ester bearing a TIPS group on the 8‐OH by using the (CuOTf) 2 · PhH complex.",10.1002/ejoc.201100034,2011-03-24,0.6080569872434174
Organic Letters,Synthesis of the Tricyclic Caged Core of Palhinine Alkaloids Based on a Non-Diels–Alder-Type Strategy,"A concise synthesis of the tricyclo[4.3.1.0 3,7 ]decane caged core of palhinine alkaloids was developed with SmI 2 -mediated cyclization and light-initiated radical addition–fragmentation as key steps. Compared with the reported racemic routes which are all based on Diels–Alder-type key reactions, our strategy would be more readily accessible to the asymmetric total syntheses of the palhinine alkaloids.",10.1021/acs.orglett.9b01898,2019-06-26,0.6080489988034341
Synlett,A Rapid Total Synthesis of (±)-Sylvone,"We report a convergent and diastereoselective synthesis of (±)-sylvone that utilizes a diastereoselective [1,3] ring contraction.",10.1055/s-2007-990926,2007-12-19,0.6080375817211608
Organic Process Research & Development,"Chemical Development of a Pilot Scale Process for the ACAT Inhibitor 2,6-Diisopropylphenyl [(2,4,6-Triisopropylphenyl)acetyl]sulfamate","A manufacturing process to prepare the ACAT inhibitor 2,6-diisopropylphenyl [(2,4,6-triisopropylphenyl)acetyl]sulfamate ( 1; CI-1011) has been developed and successfully demonstrated on a pilot scale. Commercially available 1,3,5-triisopropylbenzene ( 9 ) was chloromethylated to give 2,4,6-triisopropylbenzyl chloride ( 8 ). Cyanation of 8 under phase-transfer-catalyzed conditions followed by basic hydrolysis of the intermediate and nonisolated 2,4,6-triisopropylbenzyl cyanide ( 7 ) gave 2,4,6-triisopropylphenylacetic acid ( 2 ), a key intermediate in the convergent synthesis of 1 . Commercially available 2,6-diisopropylphenol ( 12 ) was converted to [(2,6-diisopropylphenyl)oxy]sulfonyl isocyanate ( 13 ) when reacted with chlorosulfonyl isocyanate under thermodynamically controlled conditions. Hydrolysis and decarboxylation of 13 in situ gave 2,6-diisopropylphenyl sulfamate ( 3 ), the other key intermediate. A robust process to couple 2 and 3 was developed via the intermediacy of (2,4,6-triisopropylphenyl)acetyl chloride ( 15 ) to give the final pharmaceutical product that met specifications for clinical and toxicological use. Cost, operational, safety, environmental, and equipment considerations were taken into account during the course of development.",10.1021/op9600419,1997-03-01,0.6080373627919157
Organic Letters,Enantioselective Synthesis of Schulzeines B and C via a β-Lactone-Derived Surrogate for Bishomoserine Aldehyde,"Enantioselective syntheses of the glucosidase inhibitors schulzeines B and C were achieved by employing a Pictet-Spengler reaction of a beta-lactone-derived, masked bishomoserine aldehyde. Subsequent Corey-Link reaction unveiled an alpha-azido acid enabling cyclization to the delta-lactam fused tetrahydroisoquinoline. An efficient synthesis of the trisulfate-bearing side chain featured a Noyori hydrogenation and a Sharpless dihydroxylation. An unexpected reaction of a pendant amine during a Corey-Link process opens avenues for the synthesis of proline and related amino acid derivatives.",10.1021/ol802992m,2009-02-11,0.6080332512536526
Synlett,Development of a Novel Tropomyosin Receptor Kinase Inhibitor Based on Structure–Activity Relationships: Identification of a Promising Clinical Candidate,"Abstract Tropomyosin receptor kinase (TRK) inhibitors have emerged as promising therapeutic agents for various cancers. In this study, we report the discovery and characterization of CH7070868, a novel and potent TRK-selective inhibitor. Through structure–activity relationship studies, we optimized the lead compound (CH7057288) to achieve superior TRK inhibition while reducing the risk of drug–drug interactions (CYP3A4 induction). CH7070868 demonstrated high selectivity for TRK over other kinases (KDR and LCK) and exhibited potent inhibitory activity in both biochemical and cellular assays. Our findings suggest that CH7070868 represents a promising candidate for further development as a next-generation TRK inhibitor with an enhanced efficacy.",10.1055/a-2551-5752,2025-03-05,0.6080296044602722
Organic Letters,Total Synthesis of Kingianin A,"A 12-step synthesis of kingianin A, an inhibitor of the antiapoptotic protein Bcl-xL, is based on a radical cation Diels-Alder reaction (RCDA). This approach is thought to be biomimetic. The use of a tether in the key RCDA step controls the regiochemistry of the cycloaddition, leading to the desired core structure and a separable diastereomer.",10.1021/ol303388k,2012-12-28,0.6080293632850539
Tetrahedron,A simple and efficient route to β-substituted pyrroles,,10.1016/s0040-4039(01)92377-9,1981-01-01,0.6080275055655411
Synthesis,"Aryne-Mediated Arylation of the 3-Benzazepine Scaffold: One-Pot Synthesis of 1-Aryl-3-methyl-2,3,4,5-tetrahydro-1H-3-benzazepines","The coupling of β-amino carbanions derived from 3-benz­aze­pines with in situ generated arynes has been demonstrated as a convenient route for the direct synthesis of a variety of 1-aryl-3-methyl-2,3,4,5-tetrahydro-1 H -3-benzazepines, including the biologically active drug molecule SCH 12679.",10.1055/s-0034-1380453,2015-07-09,0.6080239706939248
Organic Process Research & Development,"Synthesis of CMI-977, a Potent 5-Lipoxygenase Inhibitor","CMI-977 is a potent 5-lipoxygenase inhibitor that intervenes in the production of leukotrienes and is presently being developed for the treatment of chronic asthma. It is a single enantiomer with an all - trans (2 S,5 S ) configuration. Of the four isomers of CMI-977, the S, S isomer was found to have the best biological activity and was selected for further development. The enantiomerically pure product was synthesized on a 2-kg scale from ( S )-(+)-hydroxymethyl-γ-butyrolactone.",10.1021/op980209l,1998-12-29,0.6080142786504212
European Journal of Organic Chemistry,Asymmetric Total Synthesis of All Rugulovasine Stereoisomers and Preliminary Evaluation of Their Biological Properties,"Abstract A unified enantioselective synthesis and the biological evaluation of all rugulovasine stereoisomers are reported. The syntheses are centered on the divergent and stereochemical modular combination of each enantiomer of 4‐amino Uhle's ketone and a methacrylate derivative to build the unsaturated oxaspirolactone moiety by the Dreiding‐Schmidt reaction, followed by Fukuyama alkylation to afford the required N ‐methyl secondary amine in excellent yield. The modularity of this divergent approach, the diastereoselectivities of the reactions, and the late‐stage site‐selective methylation permit the rapid asymmetric syntheses of all rugulovasine stereoisomers, including the first total syntheses of optically pure (+)‐ and (−)‐rugulovasine B and their trideuteromethylated derivatives. All enantiopure stereoisomers of rugulovasine were tested for their binding affinities to dopamine, serotonin, and adrenergic neuroreceptors, revealing their preferred selectivity for the serotonin 1 A receptor.",10.1002/ejoc.202200315,2022-04-08,0.60801357141894
Tetrahedron,Norbornyl route to polyoxygenated cyclohexanes. A facile entry into carbasugars and shikimic acid,,10.1016/s0040-4039(98)00471-7,1998-05-01,0.6080112423294666
Angewandte Chemie International Edition,"Stereocontrolled Synthesis of (−)-5,11-Dideoxytetrodotoxin","New derivatives of an intriguing marine natural product are now accessible. The first asymmetric synthesis of the simple tetrodotoxin analogue, 5,11-dideoxytetrodotoxin (3), was achieved. Hydroxylation at position C8 of the key intermediate 1 relied on the neighboring trichloroacetamide group, and stereoselective elaboration of the vinyl group gave alpha-hydroxylactone 2, which was transformed into the title compound through a new guanidylation method.",10.1002/(sici)1521-3773(19991018)38:20<3081::aid-anie3081>3.0.co;2-6,1999-10-18,0.6080093366788734
Organic Letters,Efficient Strategy for the Construction of Both Enantiomers of the Octahydropyrroloquinolinone Ring System: Total Synthesis of (+)-Aspidospermidine,An efficient and highly stereoselective intramolecular [3 + 2] cycloaddition of nonstabilized azomethine ylide generated from a designed bicyclic aminal precursor is reported for the synthesis of both (-)- and (+)-octahydropyrroloquinolinone. One of the enantiomers is further advanced to accomplish the total synthesis of (+)-aspidospermidine.,10.1021/acs.orglett.6b00374,2016-03-21,0.6080038538362729
Organic Letters,An Enantioselective Formal Synthesis of Berkelic Acid,An enantioselective formal synthesis of berkelic acid is described. The key step involves a late-stage silyl enol ether addition to a benzannulated oxonium ion with subsequent spiroketalization leading to construction of the tetracyclic core. Thermodynamically controlled equilibration under acidic conditions affords the desired spiroketal configuration as a single diastereoisomer.,10.1021/ol202265g,2011-09-14,0.6080014476821687
Journal of Organic Chemistry,"Synthesis of Transition-State Inhibitors of Chorismate Utilizing Enzymes from Bromobenzene <i>cis</i>-1,2-Dihydrodiol","In order to survive in a mammalian host, Mycobacterium tuberculosis ( Mtb ) produces aryl-capped siderophores known as the mycobactins for iron acquisition. Salicylic acid is a key building block of the mycobactin core and is synthesized by the bifunctional enzyme MbtI, which converts chorismate into isochorismate via a S N 2″ reaction followed by further transformation into salicylate through a [3,3]-sigmatropic rearrangement. MbtI belongs to a family of chorismate-utilizing enzymes (CUEs) that have conserved topology and active site residues. The transition-state inhibitor 1 described by Bartlett, Kozlowski, and co-workers is the most potent reported inhibitor to date of CUEs. Herein, we disclose a concise asymmetric synthesis and the accompanying biochemical characterization of 1 along with three closely related analogues beginning from bromobenzene cis -1 S,2 S -dihydrodiol produced through microbial oxidation that features a series of regio- and stereoselective transformations for introduction of the C-4 hydroxy and C-6 amino substituents. The flexible synthesis enables late-stage introduction of the carboxy group and other bioisosteres at the C-1 position as well as installation of the enol–pyruvate side chain at the C-5 position.",10.1021/acs.joc.6b02801,2017-03-10,0.6079924412948928
European Journal of Organic Chemistry,"Total Synthesis of (+)‐Hyacinthacine A<sub>1</sub>, (+)‐7a‐<i>epi</i>‐Hyacinthacine A<sub>1</sub>, (6<i>R</i>)‐6‐Hydroxyhyacinthacine A<sub>1</sub> and (6<i>S</i>)‐6‐Hydroxy‐7a‐<i>epi</i>‐hyacinthacine A<sub>1</sub>","Abstract The total synthesis of natural (+)‐hyacinthacine A 1 ( 6 ), (+)‐7a‐ epi ‐hyacinthacine A 1 ( 7 ) and their 6‐hydroxy analogues 21 and 16 was achieved using a nitrone cycloaddition strategy with D ‐ribose‐derived cyclic nitrone 8 as the dipole and tert ‐butyl acrylate as the dipolarophile. After separation of the adducts, reductive cleavage of the N–O bond followed by lactam reduction and deprotection afforded the two non‐natural hydroxy analogues in excellent yields. The synthesis of (+)‐hyacinthacine A 1 ( 6 ) and of (+)‐7a‐ epi ‐hyacinthacine A 1 ( 7 ), which required deoxygenation at C(6), was accomplished by DIBAL‐H reduction of mesylate derivatives of the pyrrolizidinols 20 and 15 , respectively. Evaluation of the synthesized compounds against a panel of 12 commercially available glycosidases showed that hyacinthacine A 1 ( 6 ) and its (6 R )‐hydroxy analogue 21 are good inhibitors of amyloglucosidase; the non‐natural compound 21 is also a strong inhibitor of β‐glucosidase, while 6 showed only moderate inhibition. The non‐natural (+)‐7a‐ epi ‐hyacinthacine A 1 ( 7 ) is a moderate inhibitor of amyloglucosidase and α‐ L ‐fucosidase; the presence of the (6 S )‐hydroxy group in 16 led to diminished activity.",10.1002/ejoc.201101096,2011-10-24,0.6079866751053244
Journal of the American Chemical Society,Practical Synthesis of Macrobicyclic Thiolincosamines,"Scalable syntheses of the northern macrobicyclic thiolincosamine fragments of two structurally complex antibiotic candidates, BT-33 and cresomycin, are presented. A key transformation in each route is the highly diastereoselective addition of a putative allenylzinc nucleophile to a common Ellman sulfinimine intermediate using a zinc-promoted Barbier-type propargylation protocol that is detailed herein. These transformations proceed with dynamic kinetic resolution and use just 1.2 equiv of each respective propargyl bromide precursor.",10.1021/jacs.4c11270,2024-10-12,0.6079599871191804
Organic Letters,"A Highly Efficient, Selective, and General Method for the Synthesis of Conjugated (<i>all</i>-<i>E</i>)-Oligoenes of the (CHCH)<i><sub>n</sub></i> Type via Iterative Hydrozirconation−Palladium-Catalyzed Cross-Coupling","[reaction: see text] A linear iterative method for the construction of (all-E)-oligoenes of the (CH=CH)n type via hydrozirconation-palladium-catalyzed cross-coupling with (E)-1-bromo-4-trimethylsilyl-1-buten-3-yne is described. This method promises to provide an efficient, selective, and general route to oligoene macrolide antibiotics and other related natural products.",10.1021/ol0102794,2002-02-08,0.6079457295004104
Angewandte Chemie International Edition,Construction of a Hemifullerene Skeleton: A Regioselective Intramolecular Oxidative Cyclization,"A two-step synthesis of a strained π bowl, with hemifullerene skeleton from sumanene, was achieved in a high yield. The first step is a base-promoted condensation reaction with a benzophenone compound, bis(3,5-dimethylphenyl)methanone. The second step is the regioselective intramolecular oxidative cyclization, which is a key reaction for the hemifullerene skeleton synthesis. This regioselective cyclization is likely to be under thermodynamic control. This strategy will allow facile synthesis of various highly strained π bowls.",10.1002/anie.201500548,2015-03-10,0.6079450476656427
Organic Letters,Total Synthesis of the Conjugation-Ready Tetrasaccharide Repeating Unit of <i>Acinetobacter baumannii</i> MAR13-1452 (K125) Capsular Polysaccharide for Vaccine Development,"Acinetobacter baumannii is a highly drug-resistant pathogen that causes severe hospital infections and urgently requires new treatment strategies. Surface-exposed glycans of these bacteria have emerged as promising vaccine targets due to their immunogenic potential. Here, we report the first total synthesis of the tetrasaccharide repeating unit of Acinetobacter baumannii MAR13-1452 (K125). The presence of rare deoxy amino sugars and the exclusive 1,2- cis glycosidic linkages within the tetrasaccharide make its synthesis more challenging. A one-pot oligosaccharide assembly enabled efficient and facile synthesis of the target molecule.",10.1021/acs.orglett.5c02016,2025-06-17,0.6079362421114697
Journal of Organic Chemistry,Total Synthesis of the Boron-Containing Ion Carrier Antibiotic Macrodiolide Tartrolon B,"The first total synthesis of the boron-containing macrodiolide antibiotic tartrolon B is reported in full detail. Two convergent approaches to the target compound are described, the first of which eventually failed, due to sensitive functionality. In the second, successful route the key step was a stereoselective boron-mediated aldol addition of a bicyclic acetonide protected ketone to a diene-aldehyde. In this case the synthesis could be completed without major problems, using a Yamaguchi dimerization macrolactonization endgame.",10.1021/jo035391p,2004-01-13,0.6079296531995976
Organic Process Research & Development,Multikilogram-Scale Production of Cycloartenol Triterpenoid Glycosides as Synthetic Intermediates for a γ-Secretase Modulator,The process development and production of two cycloartenol triterpenoid glycosides on a multikilogram scale are described. The two compounds were used as key intermediates for the synthesis of a γ-secretase modulator and a novel potential therapeutic agent for Alzheimer’s disease (SPI-1865). This practical and efficient process includes extraction of precursor triterpenoid glycosides from Actaea racemosa (black cohosh) and a ZrCl 4 -catalyzed rearrangement reaction.,10.1021/op5000732,2014-04-30,0.6079269701210295
Organic Process Research & Development,Improved Process for Pilot-Scale Synthesis of Danshensu ((±)-DSS) and Its Enantiomer Derivatives,"A pilot-scale process has been developed for green and scalable synthesis of (±)-β-(3,4-dihydroxyphenyl) lactic acid ((±)-DSS) and their two important derivatives, namely, (±)-IDHP [(±)-isopropyl 2-hydroxy-3-(3,4-dihydroxyphenyl)propanoate] and (±)-DBZ [(±)-bornyl 2-hydroxy-3-(3,4-dihydroxyphenyl)propanoate]. Subsequent hydrogenation has been carried out by employing Raney Ni as catalyst. The improved process results in higher yields of 47.5% for (±)-DBZ and 49.2% for (±)-IDHP compared to the initial process with a yield of 12% for (±)-DBZ and 18% for (±)-IDHP in our original medicinal chemistry route. Furthermore, kilograms of optical DBZ [(−)- S -DBZ and (+)- R -DBZ, >99% ee] and IDHP [(−)- S -IDHP and (+)- R -IDHP, >99% ee] have been produced by chiral high-performance liquid chromatography in good yield (>84%).",10.1021/op4002593,2013-11-26,0.6079227207967227
Journal of Organic Chemistry,Asymmetric Construction of a Quaternary Carbon Center by Tandem [4 + 2]/[3 + 2] Cycloaddition of a Nitroalkene. The Total Synthesis of (−)-Mesembrine,"An efficient, total synthesis of the Sceletium alkaloid (−)-mesembrine is accomplished in seven steps and 19% yield from a functionalized nitroalkene (itself prepared in six steps and 34% yield from ethyl 3-bromopropionate). The construction of the octahydroindole framework of mesembrine features a tandem inter [4 + 2]/intra [3 + 2] cycloaddition of a 2,2-disubstituted 1-nitroalkene and a chiral vinyl ether derived from (1 R,2 S )-2-(1-methyl-1-phenylethyl)cyclohexanol as the central strategic element. The two stereogenic centers of the natural product, which include a benzylic, quaternary center, were established in 26/1 selectivity in the tandem process.",10.1021/jo970079z,1997-03-01,0.6079196616923391
Tetrahedron,A new route to -disubstituted olefins. A simple synthesis of polyunsaturated fatty acids by reiterative coupling,,10.1016/s0040-4039(01)81194-1,1984-01-01,0.6079079719781705
Journal of Organic Chemistry,Probing Host-Selective Phytotoxicity:  Synthesis of Destruxin B and Several Natural Analogues,"The syntheses of the host-selective phytotoxin destruxin B [cyclo(betaAla-Hmp-Pro-Ile-MeVal-MeAla), Hmp = (2R)-2-hydroxy-4-methylpentanoic acid], and the closely related natural analogues homodestruxin B (MeVal-->MeIle), desmethyldestruxin B (MeVal-->Val), hydroxydestruxin B (Hmp-->Dhmp, Dhmp = (2R)-2,4-dihydroxy-4-methylpentanoic acid), and hydroxyhomodestruxin B (MeVal-->MeIle, Hmp-->Dhmp) are described. In each case, the MeAla-betaAla linkage was formed by cyclization and the precursor linear hexadepsipeptides were formed by condensing two three-residue fragments. Radiolabeled samples of destruxin B, homodestruxin B, and hydroxydestruxin B were prepared by coupling [3-(14)C]-beta-alanine to the appropriate pentadepsipeptide followed by cyclization. A noteworthy feature of the synthesis involves the novel use of a Boc-hydrazide protecting group on dipeptides with a C-terminal N-methylalanine residue to inhibit the otherwise facile dioxopiperazine formation during peptide coupling.",10.1021/jo015953+,2001-10-17,0.6078756634084973
Synthesis,"A Convenient and General Route to 2-Nitro-2,3-dihydrobenzofurans",All articles of this category A facile and general two-step preparation of the hitherto unknown title compounds is reported starting from 2-(2-chloro-2-nitroethenyl)phenols. The novel 2-(2-chloro-2-nitroethyl)phenols isolated as intermediates in the synthesis are described.,10.1055/s-1988-27567,1988-01-01,0.6078588562828577
Tetrahedron,"1,3-Asymmetric induction in the intramolecular [2+2] cycloaddition of alkene-keteniminium salts. Synthesis of (+)-gibberellic acid key intermediate",,10.1016/s0040-4039(98)02228-x,1998-12-01,0.6078537226720712
Angewandte Chemie International Edition,Total Synthesis of (±)‐Photodeoxytridachione through a Lewis Acid Catalyzed Cyclization,Concerted or stepwise: The concise total synthesis of the molluscan polypropionate photodeoxytridachione (3) features a Lewis acid catalyzed cyclization of tetraenoic ester 1 to form bicylo[3.1.0]hexene 2 as a key step. The stereochemistry of the cyclization can be rationalized in terms of a stepwise or a concerted mechanism.,10.1002/anie.200390158,2003-01-30,0.6078532158766098
Journal of the American Chemical Society,Rapid Access to Spirocyclic Oxindole Alkaloids: Application of the Asymmetric Palladium-Catalyzed [3 + 2] Trimethylenemethane Cycloaddition,"The marcfortines are complex secondary metabolites that show potent anthelmintic activity and are characterized by the presence of a bicyclo[2.2.2]diazaoctane fused to a spirooxindole. Herein, we report the synthesis of two members of this family. The synthesis of marcfortine B utilizes a carboxylative TMM cycloaddition to establish the spirocyclic core, followed by an intramolecular Michael addition and oxidative radical cyclization to access the strained bicyclic ring system. In addition, the first asymmetric synthesis of (−)-marcfortine C is described. The key step involves a cyano-substituted TMM cycloaddition, which proceeds in nearly quantitative yield with high diastereo- and enantioselectivity. The resulting chiral center was used to establish all remaining stereocenters in the natural product.",10.1021/ja409013m,2013-10-01,0.6078479827216301
Tetrahedron,A stereoselective and scalable synthesis of a conformationally constrained S1P1 agonist,,10.1016/j.tetlet.2009.04.099,2009-05-05,0.6078424944143026
Tetrahedron,"A short, efficient route to 1-hydroxylated vitamin D ring A fragments",,10.1016/s0040-4039(00)74261-4,1992-07-01,0.6078316199027209
Tetrahedron,Enantioselective synthesis of bislactone structure: A formal synthesis of (−)-canadensolide,,10.1016/s0040-4039(00)97761-x,1990-01-01,0.6078261952844904
Organic Letters,Synthesis of Rhodocorane L Using Gold-Catalyzed Dearomative Spirocyclization,"High Resolution Image Download MS PowerPoint Slide Reported herein is the first total synthesis of the acorane-type terpenoid rhodocorane L, isolated from the fungus Rhodotus palmatus . This unique tricyclic scaffold containing a spiro[4.5] bicycle has antifungal activity. Key steps include diastereoselective cuprate addition, gold-catalyzed dearomative spirocyclization, and intramolecular aldol. This is the first time that a catalyst-controlled asymmetric dearomative spirocyclization has been utilized in a total synthesis. Rhodocorane L was synthesized in 17 steps, as the longest linear sequence.",10.1021/acs.orglett.5c01802,2025-06-02,0.6078173211041434
Synlett,Synthesis of Lysergic AcidMethyl Ester via the Double Cyclization Strategy,An asymmetric synthesis of (+)-lysergic acid methyl ­ester was accomplished through construction of the tetracyclic ­ergoline skeleton by double cyclization consisting of intramolecular aromatic amination and Heck reaction.,10.1055/s-0028-1087948,2009-02-24,0.6078110536867831
Journal of Organic Chemistry,Synthesis of an Achiral Isomer of Lipoic Acid As an Anchor Group for SAM Formation on Gold Surfaces,"Isolipoic acid, a symmetrical and achiral isomer of the commonly used alpha-lipoic acid, has previously been overlooked as a tether group for the formation of self-assembled monolayers (SAMs). Here its ready synthesis through a new route and its functionalization with ferrocenyl groups for redox-active SAM formation on gold electrodes are described.",10.1021/jo9024545,2010-03-08,0.6078099469620599
Tetrahedron,"A novel synthesis of a tricyclo (7.5.01,5.01,9) tetradecane ring system related to gascardic acid.",,10.1016/s0040-4039(01)86841-6,1978-01-01,0.6077914235808266
Angewandte Chemie International Edition,A Novel Aldol Condensation with 2-Methyl-4-pentenal and Its Application to an Improved Total Synthesis of Epothilone B,"The stabilization of the transition state through a favorable interaction between the double bond of 1 and the carbonyl group of 2 appears to be responsible for the high diastereoface selectivity of the aldol reaction. This key step in the highly concise total synthesis of epothilone B is followed by a Suzuki coupling to introduce the thiazole domain, a Noyori reduction to control the stereochemistry at C3, and a final macrolactonization (see reaction scheme). X=protecting group.",10.1002/(sici)1521-3773(19981016)37:19<2675::aid-anie2675>3.0.co;2-o,1998-10-16,0.6077903954319517
Organic Letters,Total Synthesis of Apoptolidin A,"A highly convergent, enantioselective total synthesis of the potent antitumor agent apoptolidin A has been completed. The key transformations include highly selective glycosylations to attach the C27 disaccharide and the C9 6'-deoxy-l-glucose, a cross-metathesis to incorporate the C1-C10 trienoate unit, and a Yamaguchi macrolactonization to complete the macrocycle. Twelve stereocenters in the polypropionate segments and sugar units were established through diastereoselective chlorotitanium enolate aldol reactions.",10.1021/ol802829n,2009-01-22,0.6077902876781025
Journal of Organic Chemistry,Total Synthesis of Bistratamide D,"The total synthesis of the macrocyclic hexapeptide bistratamide D is reported. The synthetic strategy involved assembly of enantiomerically pure oxazole, thiazole, and oxazoline segments derived from amino acids. Macrocyclization of the hexapeptidic aminooxazoline-oxazole-thiazole carboxylic acid fragment was accomplished by activation with O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HATU).",10.1021/jo981664i,1999-01-15,0.6077883318720193
Journal of Organic Chemistry,"Bi(III)-Catalyzed Synthesis of Substituted Furans from Hydroxy-oxetanyl Ketones: Application to Unified Total Synthesis of Shikonofurans J, D, E, and C","We report an improved synthetic protocol for hydroxy methyl-derived polysubstituted furans employing Bi(III)-catalyzed dehydrative cycloisomerization of α-hydroxy oxetanyl ketones. This procedure provides rapid access (within 5 min) to highly substituted furans with exceptional functional group diversity, excellent yields, generality, scalability, and operationally simple reaction conditions. Further, it demonstrated the utility of this method in the first enantioselective total synthesis of furyl-hydroquinone-derived biologically potent natural products shikonofurans J, D, E, and C in seven linear steps, starting from readily available building blocks of 2,5-dihydroxy acetophenone and 3-oxetanone employing chiral-phosphoric acid (TRIP)-catalyzed asymmetric prenylation as a key step to induce the chirality.",10.1021/acs.joc.3c00549,2023-05-11,0.6077821015568801
Tetrahedron,An efficient strategy for the iterative synthesis of a trans-fused polytetrahydropyran ring system via SmI2-induced reductive intramolecular cyclization,,10.1016/s0040-4039(99)00301-9,1999-04-01,0.6077714062243214
Organic Letters,Cross-Coupling of Cyclopropanols: Concise Syntheses of Indolizidine 223AB and Congeners,"A new synthetic method for indolizidine or pyrrolizidine alkaloids based on readily available and attractively functionalized cyclopropanols, as exemplified in concise syntheses of indolizidine (-)-223AB, its 3-epimer, (-)-indolizidine 239AB, and (-)-indolizidine 239CD, is reported. This work highlights the applications of SN2' alkylation and C-acylation of cyclopropanols to meet stereochemical challenges in natural product synthesis. Also included is diastereoselective cyclization of the resulting aminoallene adduct for bicyclic ring formation.",10.1021/ol503136s,2014-11-25,0.6077668038512929
Synlett,"Concise Synthesis of Key 3-Polyenoyl-5-methylenefuran-2,4-dione Putative Intermediates in Quartromicin Biosynthesis","Concise syntheses of two 3-polyenoyl-5-methylenefuran-2,4-diones, which are proposed to be key intermediates in the biosynthesis of the unusual 32-membered carbocycle-containing quartromicin antibiotics, are reported involving acylation of 3-lithio-4-methoxy-5-methylene-5H-furan-2-one as a key step.",10.1055/s-2008-1078247,2008-08-01,0.6077620524443932
Angewandte Chemie International Edition,"Organocatalytic, Asymmetric Total Synthesis of (−)‐Haliclonin A","The first total synthesis of the alkaloid (-)-haliclonin A is reported. The asymmetric synthesis relied on a novel organocatalytic asymmetric conjugate addition of nitromethane with 3-alkenyl cyclohex-2-enone to set the stereochemistry of the all-carbon quaternary stereogenic center. The synthesis also features a Pd-promoted cyclization to form the 3-azabicyclo[3,3,1]nonane core, a SmI2 -mediated intermolecular reductive coupling of enone with aldehyde to form the requisite secondary chiral alcohol, ring-closing alkene and alkyne metathesis reactions to build the two aza-macrocyclic ring systems, and an unprecedented direct transformation of enol into enone.",10.1002/anie.201512005,2016-02-17,0.6077595890857489
Journal of Organic Chemistry,"A Flexible Strategy for the Regiocontrolled Synthesis of Pyrazolo[1,5-<i>a</i>]pyrazines","A four-step protocol for the synthesis of pyrazolo[1,5-a]pyrazines has been developed. Commercially available pyrazoles were alkylated and formylated in a regiocontrolled manner to give pyrazole-5-aldehydes bearing 2,2-dialkoxyethyl substitution on N-1. Efficient conditions for the subsequent deprotection and cyclization of these intermediates allowed access to pyrazolo[1,5-a]pyrazines with multiple substitution patterns. The versatility of the pyrazole-5-aldehyde intermediates was further demonstrated through a deprotection and double-reductive amination sequence to give 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazines.",10.1021/acs.joc.7b02128,2017-09-26,0.6077530498277466
Tetrahedron,Asymmetric total synthesis and revision of absolute configurations of azaphilone derivative felinone A,,10.1016/j.tetlet.2017.09.090,2017-10-01,0.6077527372359305
European Journal of Organic Chemistry,"Total Synthesis of Indolizidine Alkaloids (–)‐167B, (–)‐209I, and (–)‐223A by Using a Common Tricyclic Lactone","Abstract Highly stereocontrolled total synthesis of dart frog indolizidine alkaloids (–)‐167B, (–)‐209I, and (–)‐223A was accomplished, with a common tricyclic lactone intermediate as the starting compound, in overall yields of 17 %, 14 %, and 17 %, respectively. The C7–C8 bond of the 167B, without a C8 chiral substituent, was formed through ring closure metathesis followed by hydrogenation. In 209I and 223A, which have a C8 chiral substituent, highly substrate‐controlled asymmetric radical cyclization was used to form the C7–C8 bond, and the correct stereochemistry of the C8 substituents was obtained in both molecules. Ethyl substituent at the C6 position of 223A was obtained with correct stereochemistry through asymmetric alkylation/epimerization sequences of the tricyclic lactone. Cleavage of the excess carbon on the C5 position of all three indolizidines was performed by using a Barton decarboxylation protocol. Reduction of the corresponding indolizidin‐3‐ones by LAH completed the total synthesis of (–)‐167B, (–)‐209I and (–)‐223A.",10.1002/ejoc.201500028,2015-02-09,0.6077382591143163
Journal of the American Chemical Society,Enantioselective Total Synthesis of (−)-Maoecrystal V,"The enantioselective synthesis of maoecrystal V, a cytotoxic polycyclic diterpene, is described. Key reactions in the synthesis include an intramolecular Heck reaction, an oxidative cycloetherification, and an intermolecular Diels-Alder reaction to forge the carbocyclic core in a concise and stereoselective manner. Late-stage amine and C-H oxidation is used to install the final functional groups required to complete the synthesis.",10.1021/ja5109694,2014-12-11,0.6077316842568837
Journal of Organic Chemistry,Development of a Third-Generation Total Synthesis of (+)-Discodermolide:  An Expedient Still−Gennari-Type Fragment Coupling Utilizing an Advanced β-Ketophosphonate,"[structure: see text] A novel total synthesis of the complex polyketide discodermolide, a promising anticancer agent of marine sponge origin, has been completed in 11.1% overall yield over 21 linear steps. This third-generation approach features an unprecedented Still-Gennari-type HWE olefination reaction between advanced C1-C8 beta-ketophosphonate 61 and C9-C24 aldehyde 7, introducing the (8Z)-alkene with 10:1 selectivity. The stereotetrad found in the C1-C8 subunit 61 was established via a highly diastereoselective boron-mediated aldol reaction/in situ reduction between ketone (S)-8 and 3-benzyloxypropanal. The (7S)-configuration was installed by the reduction of enone 73 with K-Selectride.",10.1021/jo050481a,2005-06-02,0.6077219231626163
European Journal of Organic Chemistry,A Practical Route to Regiospecifically Substituted (R)- and (S)-Oxazolylphenols,"New, diversely substituted phenolic oxazolines 14a−d and 15a−d were prepared by two complementary routes A and B, starting from salicylic derivatives 4−7 and various enantiomerically pure 1,2-amino alcohols 13a−d. In route A, the 1,2-amino alcohols 13a−d were directly condensed with the salicylic acids 5 and 7, using the Appel reaction, whereas in route B the amino alcohols 13b−d were treated with the 2-hydroxybenzonitriles 4 and 6, under Witte−Seeliger conditions. The latter route was advantageous for L-valinol 13b and L-tert-leucinol 13c, while route A was the method of choice for the new, sterically demanding amino alcohol 13a, prepared from D- and L-serine. The nitro group in the salicylic derivatives 5 and 6 was introduced by means of a regiospecific ipso substitution of a tert-butyl group by nitric acid. The structure of the nitro product 5 was unambiguously assigned by NOE spectroscopy on the basis of the recently developed DPFGSE-ROE pulse sequence.",10.1002/1099-0690(200108)2001:16<3067::aid-ejoc3067>3.0.co;2-0,2001-08-01,0.6077138557620876
Tetrahedron,Norbornyl route to cyclopentitols: Synthesis of trehazolamine analogues and the purported structure of salpantiol,,10.1016/s0040-4039(99)01116-8,1999-07-01,0.6077074684808983
Synlett,An Efficient and General Route to the Synthesis of Novel Aminoglycosides for RNA Binding,An alternative and straightforward method to prepare aminoglycoside dimers and heterodimeric conjugates is reported. The novel type of modification may provide a promising way for the development of new ligands effectively targeting to RNA.,10.1055/s-0030-1259305,2011-01-01,0.60769617564985
Organic Letters,Total Synthesis of (−)-Flueggeacosine C,"Herein we describe a total synthesis of the heterodimeric securinega alkaloid (−)-flueggeacosine C ( 8 ). The convergent synthetic strategy is based on a Liebeskind–Srogl cross-coupling reaction that combines a benzoquinolizidine fragment with a securinine-type alkaloid. An acyloxy nitroso ring-expansion was employed as the key step in accessing benzoquinolizidine 9, and a novel intramolecular Diels–Alder reaction of an allenic acid-containing pyridone expeditiously delivers the skeleton of the securinine-type fragment ( 16 ). Finally, a Cu-catalyzed hydroboration-oxidation sequence was employed to regio- and diastereoselectively introduce the secondary alcohol found in 8 .",10.1021/acs.orglett.4c02516,2024-08-23,0.6076955088202075
Synthesis,Synthesis of α-CH<sub>2</sub>-X Functionalized Tryptophan Methyl Ester,"All articles of this category A short and efficient synthesis of α-CH 2 -X functionalized tryptophan methyl ester (methyl 2-amino-3-(1 H -indol-3-yl)propionate) is described, by alkylation of methyl 2-isocyano-3-(1 H -indol-3-yl)propionate with a range of functionalized alkyl halides.",10.1055/s-1990-26905,1990-01-01,0.6076881235350011
Tetrahedron,Synthesis of an all-cis intermediate of ticagrelor,,10.1016/j.tetlet.2015.09.074,2015-09-21,0.6076853264987853
Organic Letters,Total Synthesis of (±)-Furanether A,"The first total synthesis of (±)-furanether A, which exhibits good antifeedant activity, has been concisely achieved in 13 linear steps. Notably, the key rigid tetracyclic skeleton containing a 1-methyl-8-oxabicyclo[3.2.1]octane moiety with two vicinal quaternary carbon centers was rapidly constructed in one step through a unique tandem C-H oxidation/oxa-[3,3] Cope rearrangement/aldol cyclization sequence.",10.1021/acs.orglett.1c03353,2021-11-03,0.6076798395265465
Organic Letters,An Efficient Synthesis of (±)-Lycoricidine Featuring a Stille−IMDAF Cycloaddition Cascade,[reaction: see text] A highly efficient total synthesis of (+/-)-Lycoricidine is described. The synthesis features the ready preparation of the Lycoricidine skeleton by a Stille-IMDAF cycloaddition cascade. The resulting cycloadduct is then used for the stereocontrolled installation of the other functionality present in the C-ring of the target molecule.,10.1021/ol052524f,2005-12-16,0.6076749324837154
Synthesis,"New Formal Syntheses of Laurencione, a Labile Dihydrofuranone Derivative from the Red Alga Laurencia spectabilis","All articles of this category A straightforward formal synthesis of the marine natural products laurencione was developed, utilizing elaboration of 5-acetoxy-3-chloropentan-2-one as the starting compound. The synthetic route consisted of (i) α -sulfenylation, (ii) α -chlorination of the resulting β -oxo sulfide, (iii) Hg 2+ -catalyzed methanolysis, (iv) methanolysis of the γ -acetoxy- α,α -dimethoxy ketone with subsequent cyclization and (v) acid hydrolysis of the acetal. Alternatively, laurencione was prepared from 1,1-dichloroacetone by a sequence of reactions involving (i) imination, (ii) regiospecific β -hydroxyethylation, (iii) hydrolysis, (iv) base-induced rearrangement of the resulting functionalized tetrahydrofuran and (v) final acid hydrolysis of laurencione methyl ether. laurencione - marine natural product - α -haloimine - α -diones - tetrahydrofurans",10.1055/s-1996-4335,1996-09-01,0.6076649021498561
Journal of Organic Chemistry,"Synthesis of a Tritium-Labeled, Fipronil-Based, Highly Potent, Photoaffinity Probe for the GABA Receptor","3-[4-[1-(2,6-dichloro-4-trifluoromethylphenyl)pyrazolo]]-3-(trifluoromethyl)diazirine is a fipronil-based (i.e. fiprole), high-affinity probe for the GABA receptor. For synthesis of the tritium-labeled version of this trifluoromethyldiazirinylfiprole ([(3)H]TDF) the required intermediate, 3-[4-[1-(2,6-dichloro-3-iodo-4-trifluoromethylphenyl)-5-iodopyrazolo]]-3-(trifluoromethyl)diazirine, was prepared in 10 steps from pyrazole and 3,5-dichloro-4-fluorobenzotrifluoride. One of the key transformations was lithiation and subsequent iodination of the 4-(2,2,2-trifluoro-1-hydroxyethyl)pyrazole intermediate. The last step involved reduction of the diiodofiprole with tritium, Pd/C, and triethylamine in ethyl acetate and afforded [(3)H]TDF with a specific activity of 15 Ci/mmol and 99% radiopurity.",10.1021/jo034520z,2003-09-13,0.6076533927103339
Organic Letters,Synthesis of the Macrocyclic Core of (−)-Pladienolide B,An efficient synthesis of the macrocyclic core of (-)-pladienolide B is disclosed. The concise route relies on a chiral auxiliary-mediated asymmetric aldol addition and an osmium-catalyzed asymmetric dihydroxylation to install the three oxygenated stereocenters of the macrocycle. This purely reagent-controlled and flexible strategy sets the stage for future analogue syntheses and structure-activity relationship plotting of the appealing anticancer lead structure pladienolide B.,10.1021/ol800946x,2008-05-30,0.6076526409977647
European Journal of Organic Chemistry,"Stereoselective Organocatalytic Approach to α,β‐Disubstituted‐β‐amino Acids: A Short Enantioselective Synthesis of Cispentacin","Abstract α‐Branched α,β‐unsaturated aldehydes have been tested in the organocatalytic tandem Michael addition/cyclization with N ‐(benzyloxycarbonyl)hydroxylamine, a reaction which until now has been restricted to α‐unsubstituted enals. Starting from cyclopentene‐2‐carbaldehyde, and using diphenylprolinol trimethylsilyl ether as a chiral amine catalyst, this approach has led to the development of a practical, high yielding (93–98 % overall yield, three steps), and highly enantioselective (up to 98:2 er ) route to the cyclic β‐amino acid cispentacin, which compares favourably with previously described asymmetric syntheses of this biologically active natural product. When using acyclic α‐branched α,β‐unsaturated aldehydes as substrates, the reaction yields depend on the substitution pattern of the aldehydes, and mixtures of cis ‐ and trans ‐isomers are obtained. Nevertheless, this strategy has proved to be successful in some instances, and (3 R ,4 R )‐benzyl 3‐ethyl‐4‐methyl‐5‐oxoisoxazolidin‐2‐carboxylate could be obtained in 70 % overall yield (two steps) from the reaction of 2‐ethylcrotonaldehyde and N ‐(benzyloxycarbonyl)hydroxylamine under catalysis with diphenylprolinol trimethylsilyl ether, and with high enantiomeric purity (99:1 er ).",10.1002/ejoc.201300197,2013-04-04,0.607652122780924
Organic Letters,Synthetic Studies on Maitotoxin. 1. Stereoselective Synthesis of the C′D′E′F′-Ring System Having a Side Chain,The stereoselective synthesis of the maitotoxin C'D'E'F'-ring system having a side chain has been accomplished through a convergent strategy. The key reactions include Horner-Wadsworth-Emmons coupling of the C'D'E'-ring and the side chain and subsequent construction of the F'-ring by silane reduction of dihydropyran.,10.1021/ol800267x,2008-04-08,0.6076520581598845
Tetrahedron,Novel synthesis of Nα-methyl-arginine and Nα-methyl-ornithine derivatives,,10.1016/0040-4039(94)02210-3,1995-01-01,0.6076436831127666
Tetrahedron,Aziridinium ions from phenylglycinol — A new approach to the synthesis of chiral diamines,,10.1016/s0040-4039(97)01019-8,1997-07-01,0.6076433836829733
Tetrahedron,"Asymmetric synthesis XIV: A short and efficient synthesis of 3,5-disubstituted pyrrolizidine alkaloids via the CN(R,S) method",,10.1016/s0040-4039(00)80305-6,1988-01-01,0.6076413523460379
Angewandte Chemie International Edition,Total Synthesis of (−)‐Salinosporamide A via a Late Stage C−H Insertion,"The synthesis of (-)-salinosporamide A, a proteasome inhibitor, is described. The synthesis highlights the assembly of a densely decorated pyrrolidinone core via an aza-Payne/hydroamination sequence. Central to the success of the synthesis is a late-stage C-H insertion reaction to functionalize a sterically encumbered secondary carbon. The latter functionalization leads to an enabling transformation where most of the prototypical strategies failed.",10.1002/anie.201900340,2019-03-19,0.6076373020013445
Synlett,Stereoselective Synthesis of the Fully Functionalized HIJ-ring Framework of Ciguatoxin,"An efficient convergent synthetic route to construct the HIJ-ring system of ciguatoxin was achieved via stereo controlled eight-membered ring formation by using acetylene cobalt complex and subsequent six-membered ring formation through intramolecular 1,4-addition reaction.",10.1055/s-2004-817769,2004-01-01,0.6076364403690897
Organic Letters,Total Synthesis of Penostatin B,The first total synthesis of penostatin B has been accomplished by using a highly diastereoselective Pauson-Khand reaction and an efficient relay ring-closing metathesis for the construction of the basic carbon skeleton of the natural product as the key steps.,10.1021/ol203021c,2011-12-06,0.6076322529993776
Journal of Organic Chemistry,"Catalytic Asymmetric Claisen Rearrangement of Gosteli-Type Allyl Vinyl Ethers: Total Synthesis of (−)-9,10-Dihydroecklonialactone B","The enantioselective synthesis of (-)-9,10-dihydroecklonialactone B is described. The catalytic asymmetric Claisen rearrangement of a Gosteli-type allyl vinyl ether was utilized to afford an acyclic α-keto ester building block endowed with functionality amenable to the preparation of the carbocyclic target molecule by suitable postrearrangement transformations: A highly diastereoselective Corey-Bakshi-Shibata reduction of a β-chiral α-keto ester and a reductive homologation of an α-hydroxy ester. A transprotection tactic by a chemoselective intramolecular 6-exo-trig iodoetherification enabled regioselective ring-closing alkene metatheses to afford the 5- as well as the 14-membered ring, however, with mixed success in terms of E/Z selectivity.",10.1021/jo5001466,2014-03-12,0.6076300952133915
Synthesis,Action of l-Aminoacylase and l-Amino Acid Oxidase on 2-Amino-3-methylpent-4-enoic acid [Δ(4)-Dehydroisoleucine and alloisoleucine] Stereoisomers: An Alternative Route to a Stereochemically Pure Compound and the Application to the Synthesis of (R)-2-Methylbutan-1-ol,,10.1055/s-1999-3565,1999-09-01,0.6076284197037347
Tetrahedron,A novel degradative strategy for the synthesis of p-quinones.,,10.1016/s0040-4039(00)85150-3,1986-01-01,0.6076262602949208
Journal of Organic Chemistry,"Total Synthesis of Ezetimibe, a Cholesterol Absorption Inhibitor","Ezetimibe (1), a strong β-lactamic cholesterol absorption inhibitor, was synthesized from (R)-6-(4-fluorophenyl)-5,6-dihydro-2H-pyran-2-one 7. Independent pathways were analyzed in order to select the optimal one, which involved 1,3-dipolar cycloaddition with C-(4-benzyloxyphenyl)-N-(4-fluorophenyl)-nitrone (8), intramolecular nucleophilic displacement at the benzylic position of the lactone, cleavage of the N-O bond, elimination of a water molecule, hydrogenation of the double bond, rearrangement of the six-membered lactone ring into a β-lactam moiety, and final deprotection of the phenolic hydroxyl group. Highly stereoselective Sc(OTf)3-catalyzed 1,3-dipolar cycloaddition was the most crucial step of the synthesis. Owing to the rigid transition state of the cycloaddition, the absolute configuration of the starting lactone controlled the formation of other stereogenic centers of the final molecule 1.",10.1021/jo400807c,2013-06-13,0.6076189338802584
Synlett,Total Chemoenzymatic Synthesis of (-)-3′-Methylaristeromycin,"Enantiopure ethyl (1S,4R)-4-hydroxy-2-methylcyclopent-2-ene-1-carboxylate, readily obtained by enzymatic kinetic resolution of the corresponding racemic derivative, provided a convenient starting building block for an 11-step chiral preparation of (-)-3′-methylaristeromycin with 23% overall yield.",10.1055/s-2007-973889,2007-04-01,0.6076173404258771
Tetrahedron,Absolute configuration of a novel glutamate receptor antagonist kaitocephalin,,10.1016/s0040-4039(01)00647-5,2001-06-01,0.6076150417199947
European Journal of Organic Chemistry,"A Novel Route to Chiral <i>trans</i>‐6‐Alkyl‐2‐hydroxymethyl‐1,2,5,6‐tetrahydropyridines by Allylation of Chiral Imines and Ring‐Closing Metathesis − Total Synthesis of (−)‐3‐<i>epi</i>‐Deoxoprosopinine","Abstract A novel route to enantiomerically pure trans ‐6‐alkyl‐2‐hydroxymethyl‐1,2,5,6‐tetrahydropyridines is reported in five steps from Garner’s aldehyde with overall yields higher than 35 %. This strategy is based on the allylation of chiral imino alcohols formed in situ followed by a ring‐closing metathesis. This new method was used for the first total synthesis of (−)‐3‐ epi ‐deoxoprosopinine. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2003)",10.1002/ejoc.200300423,2003-11-19,0.6076141128289653
Tetrahedron,"Efficient synthesis of 6-mono-bromo-1,1′-bi-2-naphthol",,10.1016/s0040-4039(02)00730-x,2002-05-01,0.6076052454289639
Synthesis,Optimized Synthesis of an Orthogonally Protected Glucosamine,"Glucosamine hydrochloride was transformed into an orthogonally protected intermediate in seven steps and 34% over­all yield. The synthesis includes an optimized preparation of N-phthaloyl-β-d-glucosamine tetraacetate, a commonly used precursor in carbohydrate chemistry.",10.1055/s-2002-20962,2002-01-01,0.6075992662367202
Tetrahedron,Synthesis of the naringinase inhibitors l-swainsonine and related 6-C-methyl-l-swainsonine analogues: (6R)-C-methyl-l-swainsonine is a more potent inhibitor of l-rhamnosidase by an order of magnitude than l-swainsonine,,10.1016/j.tetlet.2007.10.142,2007-11-27,0.6075955909912348
European Journal of Organic Chemistry,"Efficient Total Synthesis of (–)‐(3<i>S</i>,6<i>R</i>)‐3,6‐Dihydroxy‐10‐methylundecanoic Acid","Abstract An efficient enantioselective synthesis of (–)‐(3 S ,6 R )‐3,6‐dihydroxy‐10‐methylundecanoic acid ( 1 ) from epichlorohydrin is described. The key steps include Jacobsen’s HKR, Sharpless asymmetric dihydroxylation, regioselective opening of epoxide and cyclic sulfate. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2007)",10.1002/ejoc.200600690,2006-10-27,0.6075921307431505
Organic Letters,Indium-Mediated Asymmetric Intramolecular Allenylation of <i>N</i>-<i>tert</i>-Butanesulfinyl Imines: Efficient and Practical Access to Chiral 3-Allenyl-4-aminochromanes,"An efficient method for the preparation of highly optically active 3-allenyl- and 3-vinyl-4-aminochromanes by In-mediated intramolecular cyclization has been developed. The synthetic utilities of the approach were demonstrated by the construction of various chiral polycyclic heterocycles, especially the interesting spiroheterocyclic compound 9 and steroid analogue 10.",10.1021/ol501815e,2014-07-28,0.6075891757684548
Angewandte Chemie International Edition,Total Synthesis of (+)-Pyrenolide D,The direct stereoselective IIII-mediated oxidative ring contraction of a protected 6-deoxy-D-gulal substrate to form a highly functionalized tetrahydrofurfural intermediate is a key step in the first total synthesis of (+)-pyrenolide D (see scheme; R = TBS = tert-butyldimethylsilyl).,10.1002/1521-3773(20010316)40:6<1128::aid-anie11280>3.0.co;2-j,2001-03-16,0.6075840978704802
Synthesis,An Improved Synthesis of Homogentisic Acid and its Lactone,,10.1055/s-1978-24680,2002-04-05,0.6075808655267423
Synthesis,Stereoselective Total Synthesis of Paecilomycins E and F,"The stereoselective total synthesis of two bioactive resorcylic acid lactones, paecilomycins E and F has been accomplished thorough a general pathway using cis -butene-1,4-diol as the starting material. The pivotal steps of the synthesis include Sharpless asymmetric epoxidation, Bestmann–Ohira alkynation, Jacobsen kinetic resolution, and Heck coupling reaction.",10.1055/s-0034-1380400,2015-03-12,0.6075715279504567
Organic Letters,Total Synthesis of (−)-Hippodamine by Stereocontrolled Construction of Azaphenalene Skeleton Based on Extended One-Pot Asymmetric Azaelectrocyclization,"The first asymmetric total synthesis of (-)-hippodamine has been accomplished via the concise construction of its azaphenalene core, which is featured by the 2,4,6-chiral piperidine synthesis based on one-pot asymmetric azaelectrocyclization in the partially activated substituent system and the subsequent intramolecular Mannich reaction.",10.1021/ol4010917,2013-05-21,0.6075699317718405
Organic Letters,"Total Synthesis of Euplectin, a Natural Product with a Chromone Fused Indenone","The first total synthesis of euplectin, a rare metabolite with a chromone annulated indenone motif, has been accomplished in 17 steps. This has been possible through interplay among three key reactions: a Hauser sulfoxide annulation, a new chromone formation and a late-stage retro-Diels-Alder reaction. The entire regiochemical integrity of the successful route is established by an iodine-catalyzed aromatization of a cyclohexane-1,3-dione and the Hauser annulation.",10.1021/ol901817r,2009-09-08,0.6075689225338791
Synthesis,"Asymmetric Synthesis of 3,3′-Pyrrolidonyl Spirooxindole-5′-Carboxylic Ester from l-Tryptophan","Abstract A highly efficient, multi-gram scale asymmetric synthesis of 3,3′-pyrrolidonyl spirooxindole-5′-carboxylic ester, which could be a potential precursor for the synthesis of cyanogramide, is accomplished from commercially available l-1-methyltryptophan in two pots. Fluoride-promoted desilylative spiro-cyclization of (semi) in situ generated isocyanate derived from l-1-methyltryptophan is the key reaction. Further, a variety of arene-substituted 3,3′-pyrrolidonyl spirooxindole-5′-carboxylxic acid esters were synthesized by late stage functionalization of easily accessible 3,3′-pyrrolidonyl spirooxindole-5′-carboxylic ester.",10.1055/a-2444-0067,2024-10-16,0.6075666668153299
Organic Letters,Solving a Mystery with Classical and Dual Photoredox Catalysis: Application of Nickel in the Synthesis of Ergot Alkaloids,"A short synthesis of the ergot alkaloid lysergene and a formal total synthesis of lysergic acid diethylamide (LSD) under the avoidance of palladium and including two nickel-catalyzed steps instead have been developed. A key intermediate of this approach has already been reported by Hendrickson et al. in 2004 (Hendrickson, J.B. et al. Org. Lett. 2004, 6, 3–5), yet the spectral data do not match, adding to doubts about the course of their route. While the final steps of the Hendrickson synthesis could not be reproduced, we were able to leverage the elusive intermediate.",10.1021/acs.orglett.4c01291,2024-05-10,0.6075649834146538
Journal of Organic Chemistry,The Enantiospecific Synthesis of an Isoxazoline. A RGD Mimic Platelet GPIIb/IIIa Antagonist,"A convergent, large-scale, chiral synthesis of isoxazoline 1 has been achieved in 37% overall yield and >99.6% optical purity, starting from L-asparagine and 4-cyanobenzaldehyde. Hofmann reaction of N(alpha)-n-Boc-L-asparagine with iodosobenzene diacetate provides optically pure N(alpha)-n-Boc-L-alpha,beta-diaminopropionic acid (8) in 75% yield. A process of lipase resolution-base catalyzed epimerization gives the single enantiomer 5. Reaction of acid 5 with amine 9 in the presence of thionyl chloride forms the framework of 1. A Pinner reaction of intermediate 4 in methyl acetate or anisole, followed by an amidination with ammonium acetate, gives optically pure product 1.",10.1021/jo9612537,1997-04-01,0.6075629522172183
Organic Letters,"Enantiopure 2,3-Dihydro-4-pyridones as Synthetic Intermediates:  A Concise Asymmetric Synthesis of (+)-Allopumiliotoxin 267A",[figure: see text] A concise asymmetric synthesis of (+)-allopumillotoxin 267A has been accomplished using an enantiopure dihydropyridone building block. The synthesis is highly stereoselective and requires 10 steps from readily available material.,10.1021/ol0069709,2001-01-10,0.6075602965010968
Organic Process Research & Development,Development of Manufacturing Processes for the Carboxylic Acid Key Intermediate of Lusutrombopag: One-Pot Reaction Process of Formylation and the Horner–Wadsworth–Emmons Reaction,"We describe the development of a one-pot preparation process of ( E )-3,5-dichloro-4-(3-ethoxy-2-methyl-3-oxoprop-1-en-1-yl)benzoic acid ( 3 ), which is a key carboxylic acid intermediate of lusutrombopag. This one-pot reaction process is composed of lithiation of 3,5-dichlorobenzoic acid with lithium diisopropylamide (LDA), formylation using N -formylmorpholine, followed by olefination employing the Horner–Wadsworth–Emmons reaction with triethyl 2-phosphonopropionate. This method enabled kilogram-scale manufacturing of carboxylic acid 3, a key intermediate of lusutrombopag with high purity, together with a reduced number of steps, improvement of yield, and avoidance of a cumbersome procedure for isolation of the intermediate.",10.1021/acs.oprd.0c00311,2020-09-22,0.6075555145536213
Synthesis,The First Synthesis of a Diynone from<i>Echinacea pallida</i>,"In order to provide an authentic standard and to generate pure material for biological testing, an efficient synthetic route to 1 was developed. This represents the first total synthesis of a major bioactive diynone from E. pallida.",10.1055/s-2005-918418,2005-01-01,0.6075535982734566
Journal of Organic Chemistry,"Total Synthesis of (±)-Clivonine via Diels–Alder Reactions of 3,5-Dibromo-2-pyrone","New synthetic routes to (±)-clivonine were devised starting with the Diels-Alder cycloadditions of 3,5-dibromo-2-pyrone with styrene pinacol boronate dienophiles. In the first-generation synthesis, the pivotal perhydroindoline system including the C5-hydroxyl group was constructed via a reaction sequence involving the Eschenmoser-Claisen rearrangement and regio/stereoselective epoxide opening reaction. In the second-generation synthesis, a radical-mediated cyclization approach was employed for the rapid assembly of the pyrrolidine ring. In this route, the C5-hydroxyl group provided by the dienophile in a stereochemically defined form was preserved throughout the synthesis.",10.1021/acs.joc.0c01283,2020-07-02,0.6075423615494555
Tetrahedron,"Structure of kaitocephalin, a novel glutamate receptor antagonist produced by Eupenicillium shearii",,10.1016/s0040-4039(97)01653-5,1997-10-01,0.6075356269419022
Organic Letters,Total Synthesis of GEX1A,"An efficient and readily modifiable synthesis of GEX1A/herboxidiene/TAN-1609 ( 1) was developed. This modular synthesis featured a Suzuki coupling to install the conjugated diene and a Ru-catalyzed lactonization and Roush crotylation to construct the functionalized tetrahydropyran moiety. Myers' alkylation, cross-metathesis, and Keck crotylation were employed for assembly of the biologically essential side-chain domain.",10.1021/ol800902g,2008-07-19,0.6075332524065467
Journal of Organic Chemistry,Synthetic Endeavors toward 2-Nitro-4-Alkylpyrroles in the Context of the Total Synthesis of Heronapyrrole C and Preparation of a Carboxylate Natural Product Analogue,"The synthesis of 2-nitro-4-oligoprenyl-substituted pyrrole derivatives relevant to the heronapyrroles and related natural products was investigated. Among numerous approaches, nitration of a 3-farnesyl-substituted unprotected pyrrole using AcONO2 gave the best results, albeit still with unsatisfactory yield and regioselectivity. Therefore, the synthesis of (-)-heronapyrrole C acid, an analogue of the naturally occurring antibiotic heronapyrrole C carrying a bioisosteric carboxylate in place of the nitro group, was examined. In lieu of the unsatisfactory nitration, a regioselective acylation with Cl3CCOCl was carried out (>8:1 regioselectivity, in contrast to the 1:1.3 ratio for the nitration). The trichloromethyl ketone was converted to the desired acid in a haloform reaction at the final stage of the synthesis. Further key steps of the analogue synthesis involved a position- and stereoselective Corey-Noe-Lin dihydroxylation and an organocatalytic double Shi epoxidation. A biomimetic polyepoxide cyclization cascade established the bis-THF backbone. Thus, (-)-heronapyrrole C acid was synthesized in eight steps (14.5% overall yield) from commercially available starting materials.",10.1021/jo402240g,2013-12-04,0.6075183778165874
Synthesis,A Synthetic Entry to the Trichothecene Nucleus via Cargill Rearrangement. Formal Synthesis of (±)-Verrucarol,,10.1055/s-1998-5933,1998-03-01,0.6075160722548196
Journal of the American Chemical Society,Asymmetric Total Synthesis of Caribenol A,"A unified strategy toward the asymmetric total synthesis of carbenol A is reported, featuring intramolecular Diels-Alder (IMDA) and biomimetic oxidation reactions as key steps.",10.1021/ja106585n,2010-09-10,0.6075106092173349
Synlett,"First Total Synthesis of (3R,4S)-4-Hydroxylasiodiplodin: A Facile and Stereoselective Approach","A first total synthesis of (3 R ,4 S )-4-hydroxylasiodiplodin is described starting from methyl acetoacetate and a commonly available carbohydrate, d -mannitol, which is regularly used in organic synthesis. The facile and stereoselective approach involves the Barbier allylation and a ring-closing metathesis as key steps.",10.1055/s-0032-1317805,2013-04-12,0.6074925856777064
Organic Letters,"A Convergent and Highly Efficient Synthesis of (<i>E,Z</i>)-2,13-Octadecadienyl Acetate and (<i>E,Z</i>)-3,13-Octadecadienyl Acetate, Components of the Sex Pheromone of the Leopard Moth <i>Zeuzera pyrina</i>, through Sulfones","A new, convergent synthesis of ( E,Z )-2,13-octadecadienyl acetate ( 1 ) and ( E,Z )-3,13-octadecadienyl acetate ( 2 ), the two key components of the leopard moth Zeuzera pyrina, from 2-chloromethyltetrahydrofuran in good overall yields and stereomeric purity is reported. The synthesis of both components utilizes the common intermediate sulfone 12 as a convenient building block to be coupled with iodoacetylenic derivatives 9 or 17 in the key step.",10.1021/ol990114j,1999-08-31,0.6074904203978821
Journal of Organic Chemistry,Formal Total Syntheses of (−)- and (+)-Actinophyllic Acid,"The formal total syntheses of (-)-actinophyllic acid and its enantiomer starting from the same chiral intermediate are reported. The synthesis features a photoredox organocatalytic asymmetric alkylation to generate the original C15 chirality, a photocatalytic C-H functionalization of 3-methylindole in flow for constructing the C16 all-carbon quaternary center, a regioselective 1,3-dipolar cycloaddition, and an intramolecular Henry reaction to assemble the pentacyclic core of the target molecule.",10.1021/acs.joc.7b02747,2017-12-28,0.607489219448849
Tetrahedron,"A total synthesis of oxetanocin, a novel nucleoside with an oxetane ring",,10.1016/s0040-4039(00)80596-1,1988-01-01,0.6074795022937794
Tetrahedron,"Synthetic studies towards paraherquamide F: synthesis of the 1,7-dihydropyrano[2,3-g]indole ring system",,10.1016/s0040-4039(02)00220-4,2002-03-01,0.6074738021238655
Organic Letters,"Synthesis of New 2‘,3‘-Dideoxy-6‘,6‘-difluoro-3‘-thionucleoside from <i>g</i><i>em</i>-Difluorohomoallyl Alcohol","[reaction: see text] 2',3'-Dideoxy-6',6'-difluoro-3'-thionucleoside 1b, an analogue of 3Tc that has high biological activities against HIV and HBV, has been synthesized from gem-difluorohomoallyl alcohol 3 in an efficient way. The key intermediate 4-amino-3,3-difluorotetrahydrothiophen-2-ylmethyl benzoate 15 was prepared from 2,2-difluoro-1-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]but-3-en-1-ol 3 in 11 steps. The construction of pyrimidine ring with the amino group of compound 15 gave the target compound 1.",10.1021/ol048423j,2004-09-30,0.6074714791205904
Synlett,Preparation of Novel 4′-Spirocyclopropyl Nucleoside Analogues,"Abstract The stereoselective preparation of a novel 4′-spirocyclopropyl nucleoside analogue has been developed by using a semibenzilic Favorskii rearrangement of a 4′-(2-chloro-3-oxocyclobutyl)spirofuranose as a key step. These chiral spirocyclic intermediates, readily obtained on a multigram scale from chiral-pool starting materials, were shown to be highly suitable precursors for achieving full stereoselectivity in the reduction–ring contraction sequence. The downstream introduction of a nucleobase through Vorbrüggen glycosylation successfully resulted in the formation of the corresponding novel 4′-spirocyclic nucleoside analogue in a stereospecific manner.",10.1055/a-1386-7194,2021-02-09,0.6074711915071006
Angewandte Chemie International Edition,Asymmetric Total Synthesis of (−)‐Cribrostatin 4 (Renieramycin H),Out of the blue: The convergent asymmetric total synthesis of the antitumor antibiotic (−)-cribrostatin 4 from the blue sponge Cribrochalina features asymmetric Staudinger and Pictet–Spengler reactions to form the tetrahydroisoquinoline moiety. These reactions were followed by a reductive opening/elimination of a tricyclic β-lactam and a Pictet–Spengler cyclization to access the unsaturated pentacyclic core.,10.1002/anie.200604126,2007-01-19,0.6074536245387744
Organic Letters,Efficient Synthesis of the C<sub>1</sub>−C<sub>11</sub> Fragment of the Tedanolides. The Nonaldol Aldol Process in Synthesis,[reaction: see text] The nonaldol aldol process developed in our laboratories has been applied to the synthesis of a C(1)-C(11) fragment 22 of the novel macrocyclic cytotoxic agents tedanolide and 13-deoxytedanolide 1 and 2. The commercially available hydroxy ester 7 was converted in 24 steps into compound 22 using two nonaldol aldol reactions.,10.1021/ol005675l,2000-05-19,0.6074534377347918
Journal of Organic Chemistry,"Enantioselective Total Synthesis of the (−)-(6<i>R</i>,11<i>R</i>,14<i>S</i>)-Isomer of Colletallol","The total synthesis of the (−)-(6 R,11 R,14 S )-isomer of colletallol was achieved in 15 steps. The key steps of the sequence were the building of the macrocycle via two consecutive Wittig reactions, the first intermolecular and the second intramolecular, instead of the classical macrolactonization methods.",10.1021/jo970020s,1997-09-01,0.6074519588852642
Synlett,Total Stereocontrolled Synthesis of Lipoxin B<sub>4</sub>,"All articles of this category An efficient convergent synthesis of lipoxin B 4 was achieved by coupling two chiral synthons : the diol 2 easily prepared from the acetylenic diol 4 and the allylic alcohol 3 , followed by stereoselective reduction of the trienynetriol 10 with activated zinc.",10.1055/s-1993-22408,1993-01-01,0.6074510513291901
Tetrahedron,Synthesis of an austrodorane sesquiterpenoid core via a transannular Prins cyclization,,10.1016/j.tetlet.2011.01.093,2011-02-01,0.6074471349242233
Synlett,Total Synthesis of Diospongin A via an Enzymatic Kinetic Resolution of (±)-Tetrahydropyranol Derived from Prins Cyclization,A concise and efficient total synthesis of diospongin A is described; it utilizes Prins cyclization and enzymatic kinetic re­solution as key steps. This is the first report on the synthesis of ­diospongin A by means of lipase-mediated transesterification of (±)-tetrahydropyranol derived from Prins cyclization.,10.1055/s-2007-984886,2007-07-12,0.6074467325760526
European Journal of Organic Chemistry,"A Platform of Regioselective Methodologies to Access Polysubstituted 2‐Methyl‐1,4‐naphthoquinone Derivatives: Scope and Limitations","Abstract A platform of synthetic methodologies has been established to access a focused library of polysubstituted 3‐benzylmenadione derivatives functionalized on the aromatic ring of the naphthoquinone core. Two main routes were explored: 1) The naphthol route, starting from either an α‐tetralone or a propiophenone, and 2) the regioselective Diels–Alder reaction, starting from various dienes and two 2‐bromo‐5(or 6)‐methyl‐1,4‐benzoquinones. 6‐Substituted 2‐methylnaphthols were synthesized by using a xanthate‐mediated free‐radical addition/cyclization sequence for the construction of the 6‐substituted menadione subunit. Furthermore, an efficient and simple new pathway that allows the formation of 6‐ or 7‐substituted 3‐(substituted‐benzyl)menadione regioisomers from a common commercial scaffold has also been developed by the naphthol route, advantageous with regard to step economy. Our synthetic methodologies exemplified by 34 compounds have allowed structure–activity relationships to be deduced for use as the basis for the development of new antimalarial redox‐active polysubstituted benzylmenadione derivatives.",10.1002/ejoc.201600144,2016-03-21,0.607442124844785
Journal of the American Chemical Society,Asymmetric Synthesis of Dihydroindanes by Convergent Alkoxide-Directed Metallacycle-Mediated Bond Formation,"A convergent synthesis of highly substituted and stereodefined dihydroindanes is described from alkoxide-directed Ti-mediated cross-coupling of internal alkynes with substituted 4-hydroxy-1,6-enynes (substrates that derive from 2-directional functionalization of readily available epoxy alcohol derivatives). In addition to describing a new and highly stereoselective approach to bimolecular [2 + 2 + 2] annulation that delivers products not available with other methods in this area of chemical reactivity, evidence is provided to support annulation by way of regioselective alkyne-alkyne coupling, followed by metal-centered [4 + 2] rather than stepwise alkene insertion and reductive elimination. Overall, the reaction proceeds with exquisite stereochemical control and defines a convenient, convergent, and enantiospecific entry to fused carbocycles of great potential value in target-oriented synthesis and medicinal chemistry.",10.1021/ja2105043,2012-01-10,0.6074355753161075
Organic Process Research & Development,Improved Process for the Preparation of 1-Benzhydrylazetidin-3-ol: Development of an Efficient Synthesis and Identification of Process-related Impurities and/or Intermediates,"An improved, one-pot, and multikilogram-scale synthesis of 1-benzhydrylazetidin-3-ol, the pharmaceutically important moiety, has been developed. The improved process for the preparation of 1-benzhydrylazetidin-3-ol was able to minimize a content of impurities and allows the effective production of 1-benzhydrylazetidin-3-ol and its scale-up. The process was high yielding (80%) and chromatography-free with purity 99.3 area %.",10.1021/op100100y,2010-06-28,0.6074355346141328
Angewandte Chemie International Edition,Enantioselective Organocatalytic Michael/Aldol Sequence: Anticancer Natural Product (+)‐<i>trans</i>‐Dihydrolycoricidine,"A total synthesis of the anticancer natural product (+)-trans-dihydrolycoricidine is reported from α-azidoacetone and cinnamaldehyde precursors. Key elements include an asymmetric organocatalytic sequence proceeding by a regiospecific secondary-amine-catalyzed syn Michael addition followed by an intramolecular aldol reaction. The sequence results in the formation of an advanced intermediate, containing three stereogenic centers, in one step which and was converted into the title compound in eight steps.",10.1002/anie.201403065,2014-06-20,0.6074351940847138
Organic Letters,"Efficient and Scalable One-Pot Synthesis of 2,4-Dienols from Cycloalkenones: Optimized Total Synthesis of Valerenic Acid","A mild and selective one-pot procedure to provide 2,4-dienols from simple cycloalkenones in high yields is described. This transformation is based on the in situ formation of acid-labile allylic alcohols, which on treatment with trifluoroacetic acid undergo a formal [1,3]-hydroxy migration to form diastereo- and enantiomerically enriched 2,4-dienols. The usefulness of this protocol is demonstrated in a short synthesis of valerenic acid.",10.1021/ol202170c,2011-09-06,0.6074282802942148
European Journal of Organic Chemistry,Asymmetric Total Synthesis and Biological Evaluation of Proapoptotic Natural Myrcene‐Derived Cyclohexenyl Chalcones,"Based on a bioinspired asymmetric Diels–Alder cycloaddition using a chiral Evans oxazolidinone, the first total synthesis of both enantiomers of two myrcene‐derived cyclohexenyl chalcones, fislatifolione and fislatifolic acid, has been carried out. This strategy was also applied to the total synthesis of nicolaiodesin C. These natural products, as well as their synthetic intermediates, were evaluated by in‐vitro affinity displacement assays, based on the modulation of Bcl‐xL/Bak, Mcl‐1/Bid, and Bcl‐2‐Bim interactions. This study showed that (+)‐fislatifolic acid acts as a dual Bcl‐xL/Mcl‐1 inhibitor with micromolar activity, and that a Weinreb amide intermediate acts as an excellent Mcl‐1/Bcl‐2 dual inhibitor at the submicromolar level.",10.1002/ejoc.201800262,2018-05-17,0.6074235272021993
Tetrahedron,"A route to 2,2-dihydro-5-imino-1,2-oxaphosphol-3-enes",,10.1016/s0040-4039(00)81785-2,1983-01-01,0.6074231977116209
Organic Letters,Total Synthesis of (−)-Kaitocephalin Based on a Rh-Catalyzed C–H Amination,"A total synthesis of (-)-kaitocephalin, an ionotropic glutamate receptor antagonist, is accomplished in highly stereocontrolled manner via Overman rearrangement, rhodium-catalyzed benzylic C-H amination, pyrrolidine formation involving nucleophilic opening of a cyclic sulfamate, and rhodium-catalyzed allylic C-H amination as key steps.",10.1021/ol300431n,2012-03-05,0.6074141634448609
European Journal of Organic Chemistry,Efficient Synthesis of 2‐Amino‐1‐Arylethanols Through a Lewis Base‐Catalyzed SiCl<sub>4</sub>‐Mediated Asymmetric Passerini‐Type Reaction,"We herein report, a practical and efficient strategy for the synthesis of enantiomerically enriched 2‐amino‐1‐arylethanols, a structural motif commonly encountered in the family of β‐adrenergic blockers or agonists, through a Lewis base‐catalyzed SiCl 4 ‐mediated asymmetric Passerini‐type reaction of isocyanides with aldehydes. The protocol features a simple one‐pot, two‐step procedure, the use of commercially available starting materials, a broad functional group tolerance, and high levels of selectivity up to 98.5:1.5 er . Application to the synthesis of the salbutamol acetate salt, a drug widely used as a bronchodilator to manage asthma and other chronic obstructive airway diseases is also reported.",10.1002/ejoc.202001172,2020-10-28,0.6074094719328392
European Journal of Organic Chemistry,A Concise and Efficient Synthesis of <i>seco</i>‐Duocarmycin SA,"Abstract A short and efficient synthesis of seco ‐duocarmycin SA ( 3 ), a highly potent cytostatic agent and direct precursor of the natural product duocarmycin SA ( 1 ), has been achieved. Starting from commercially available 2‐methoxy‐4‐nitroaniline ( 4 ) the synthetic protocol contains a Fischer indole synthesis to introduce the heterocyclic scaffold and a radical 5‐ exo ‐ trig cyclization to furnish the (chloromethyl)indoline ring system as key reactions. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2003)",10.1002/ejoc.200390094,2003-01-15,0.6074080900315777
European Journal of Organic Chemistry,A Practical Synthesis of Rosuvastatin and Other Statin Intermediates,Abstract The efficient aldol condensation between a derivative of methyl 3‐hydroxy‐5‐oxohexanoate and a pyrimidinecarbaldehyde comprising the core structure of rosuvastatin has been developed as an alternative approach to the classical methods employing ylides for the synthesis of rosuvastatin. The formation of a double bond connecting the aromatic part with the side chain of the statin was effectively promoted by using a strong Lewis acid which provided the optimum result in combination with a tertiary amine. The method was also successfully applied to the synthesis of pitavastatin.,10.1002/ejoc.201500356,2015-05-27,0.6074045080593478
Organic Letters,Epoxide-Initiated Electrophilic Cyclization of Azides:  A Novel Route for the Stereoselective Construction of Azabicyclic Ring Systems and Total Synthesis of (±)-Indolizidine 167B and 209D,"[reaction: see text] A novel and general method for the stereoselective construction of 5-hydroxymethyl azabicyclic ring skeletons based on epoxide initiated electrophilic cyclization of azides has been developed and applied in the synthesis of (+/-)-indolizidine 167B and 209D with an overall yield of 16.5% and 17.8%, respectively. The efficiency of this methodology is further exemplified in the synthesis of azepine skeleton via tandem cation-olefin-azide cyclization.",10.1021/ol027563v,2003-01-18,0.6074014732009291
Journal of Organic Chemistry,Total Synthesis of Brevisamide Using an Oxiranyl Anion Strategy,"A total synthesis of brevisamide, a marine monocyclic ether amide isolated from the dinoflagellate Karenia brevis, has been achieved in 18 steps starting from 4-(benzyloxy)butanol. The synthesis involves oxiranyl anion coupling between an epoxy sulfone and a triflate, intramolecular etherification of a hydroxy-bromoketone, diastereoselective introduction of the axial methyl group by hydroxyl-directed hydrogenation of an exocyclic olefin, and installation of an acetamide side chain by nucleophilic substitution of an N-acetyl carbamate. The dienal side chain is assembled using a Horner-Wadsworth-Emmons reaction to complete the synthesis.",10.1021/acs.joc.6b00484,2016-04-09,0.6073840859372802
Tetrahedron,Synthesis and reduction of chiral sulfinyl cyclohexanones,,10.1016/s0040-4039(00)96645-0,1987-01-01,0.6073808607034193
Tetrahedron,"Total synthesis of methyl 14-hydroxy-(all-cis)-5,8,11-tetradecatrienoate: A useful intermediate for the synthesis of arachidonic acid analogues",,10.1016/s0040-4039(97)10607-4,1998-02-01,0.6073770757146479
Synlett,First Total Synthesis of Dermocanarin 2,"The first total synthesis of dermocanarin 2 is described. The synthesis features the construction of the anthraquinone and naphthoquinone frameworks through annulation reactions onto an axially chiral biphenyl intermediate, obtained by an enzyme-catalyzed enantioselective desymmetrization of a σ-symmetric precursor, followed by a stereoselective aldol reaction to construct the stereogenic center in the side chain.",10.1055/s-0035-1561417,2016-03-24,0.6073687848447078
Synlett,1-Trifluoromethyl-1-diethoxyphosphoryl Carbene: A New Synthon for the Preparation of CF<sub>3</sub>-Containing α-Hydroxy and α-Amino Phosphonic Acid Derivatives,"The first synthesis of diethyl 1-diazo-2,2,2-trifluoroethylphosphonate has been developed starting from readily available compounds. The synthetic utility of this compound is demonstrated via its Rh-catalyzed insertion into O-H and N-H bonds to produce CF3-substituted α-hydroxy phosphonic and α-amino phosphonic acid derivatives",10.1055/s-2006-939704,2006-05-22,0.6073655775471906
Angewandte Chemie International Edition,The Total Synthesis of Spirotryprostatin A,"Eight concise steps suffice for the first total synthesis of the title compound 1, which inhibits the transitions from the G2 and M phases into the next phases of the cell cycle. Key steps in the synthesis are a stereocontrolled oxidative rearrangement of an indole to form the chiral spiroindolinone nucleus and a regioselecitve sulfoxide elimination.",10.1002/(sici)1521-3773(19980504)37:8<1138::aid-anie1138>3.3.co;2-e,1998-05-04,0.6073651124282122
Angewandte Chemie International Edition,The Total Synthesis of Spirotryprostatin A,"Eight concise steps suffice for the first total synthesis of the title compound 1, which inhibits the transitions from the G2 and M phases into the next phases of the cell cycle. Key steps in the synthesis are a stereocontrolled oxidative rearrangement of an indole to form the chiral spiroindolinone nucleus and a regioselecitve sulfoxide elimination.",10.1002/(sici)1521-3773(19980504)37:8<1138::aid-anie1138>3.0.co;2-n,1998-05-04,0.6073651124282122
Angewandte Chemie International Edition,"Secupyritines A‐C, Three Natural Propellane <i>Securinega</i> Alkaloids: Structure Elucidation and Total Synthesis Based on Biogenetic Building Blocks","Abstract Secupyritines A‐C are unique polycyclic Securinega alkaloids isolated from medicinal plant Flueggea suffruticosa . They feature a distinctive 6/6/6/5/6 fused pentacyclic ring system with a highly strained 2‐oxa‐6‐aza[4.4.3]propellane core. Their structures with absolute configurations were elucidated through a comprehensive approach involving nuclear magnetic resonance (NMR) spectroscopy, single‐crystal X‐ray crystallography, electronic circular dichroism (ECD) calculations, and total synthesis. The total synthesis of secupyritines A‐C was achieved in 14 or 16 steps, employing a synthesis strategy based on biogenetic building blocks. Key elements of the synthetic procedures include a vinylogous Mannich‐type reaction to construct the sp 3 ‐sp 2 attached‐ring system, a Suzuki coupling reaction to build the piperidine ring, and an intramolecular aza ‐Michael addition reaction to establish the propellane skeleton. Formal asymmetric synthesis of secupyritines A‐C was also presented.",10.1002/anie.202423900,2025-01-04,0.6073643651346504
Angewandte Chemie International Edition,Total Synthesis and Reassessment of the Phosphatase‐Inhibitory Activity of the Antitumor Agent TMC‐69‐6H,The unexpected selectivity profile of (17R)- and (17S)-TMC-69-6H (see formula) suggests that N-hydroxypyridone derivatives constitute a promising new lead structure in the search for selective phosphatase inhibitors. An unprecedented Pd-catalyzed CC bond formation to a pyranone derivative was a key step in the synthesis of enantiopure (17R)- and (17S)-TMC-69-6H.,10.1002/anie.200352268,2003-11-04,0.6073557921615655
Journal of the American Chemical Society,Concise Enantiospecific Total Synthesis of Tubingensin A,We report the enantiospecific total synthesis of (+)-tubingensin A. Our synthesis features an aryne cyclization to efficiently introduce the vicinal quaternary stereocenters of the natural product and proceeds in only nine steps (longest linear sequence) from known compounds.,10.1021/ja501142e,2014-02-14,0.6073467927413748
Journal of Organic Chemistry,Total Synthesis of a CD-Ring: Side-Chain Building Block for Preparing 17-<i>epi</i>-Calcitriol Derivatives from the Hajos–Parrish Dione,An efficient synthesis of the key building block for 17-epi-calctriol from the Hajos-Parrish dione involving a sequence of diastereoselective transformation of the azulene core and the side-chain construction is presented.,10.1021/jo201083w,2011-07-04,0.6073451685803457
Tetrahedron,Studies on the total synthesis of the saponaceolides. 1. Enantioselective synthesis of the spiroketal subunit,,10.1016/s0040-4039(99)00366-4,1999-04-01,0.607344207825345
Tetrahedron,Studies on the total synthesis of the saponaceolides. 2. Enantioselective synthesis of 2-epi-saponaceolide B,,10.1016/s0040-4039(99)00367-6,1999-04-01,0.607344207825345
Organic Letters,An Approach toward Constructing the Trioxadispiroketal Core in the DEF-Ring of (+)-Spirastrellolide A,"A concise and stereoselective synthesis of the trioxadispiroketal motif that embodies the DEF-ring of the marine macrolide (+)-spirastrellolide A is described. The synthetic approach features a sequence of cyclic acetal tethered ring-closing metathesis and Suárez oxidative cyclization, thereby constituting a viable strategy for constructing the Northern Half.",10.1021/ol502103b,2014-08-14,0.6073431473334409
Organic Letters,"Cobalt-Catalyzed Synthesis of Unsymmetrically <i>N</i>,<i>N</i>-Disubstituted Formamides via Reductive Coupling of Primary Amines and Aldehydes with CO<sub>2</sub> and H<sub>2</sub>","Herein, a novel route to synthesize unsymmetrically N, N -disubstituted formamides is reported, which is achieved via reductive coupling of primary amine and aldehyde with CO 2 /H 2 over a cobalt-based catalytic system composed of CoF 2, P(CH 2 CH 2 PPh 2 ) 3 and K 2 CO 3 . The mechanism investigation indicates that a secondary amine is formed via hydrogenation of the imine originated from aldehyde and primary amine, which further reacts with HCOOH generated from CO 2 hydrogenation, resulting in the formation of NNFA finally.",10.1021/acs.orglett.8b02384,2018-10-22,0.6073423847821768
Angewandte Chemie International Edition,"Enantioselective Synthesis of Oasomycin A, Part II: Synthesis of the C29–C46 Subunit","Putting the pieces together: The total synthesis of the natural macrolide oasomycin A has been realized. Key fragment couplings include an anti-Felkin selective aldol addition (green), Kociensky–Julia olefinations (red), and competitive Weinreb amide acylation reaction (blue). The utility of the 4,5-diphenyloxazole as a carboxy surrogate and the late-stage macrolactonization affording the 42-membered macrocycle of oasomycin A are also described.",10.1002/anie.200603654,2006-12-08,0.6073383673181938
Organic Letters,Synthesis of Enantioenriched α-Chiral Bicyclo[1.1.1]pentanes,"Bicyclo[1.1.1]pentanes (BCPs), useful surrogates for para-substituted arenes, alkynes, and tert-butyl groups in medicinal chemistry, are challenging to prepare when featuring stereogenic centers adjacent to the BCP. We report the development of an efficient route to α-chiral BCPs, via highly diastereoselective asymmetric enolate functionalization. We also describe the application of this chemistry to the synthesis of BCP analogues of phenylglycine and tarenflurbil, the single enantiomer of the NSAID flurbiprofen.",10.1021/acs.orglett.9b00691,2019-03-14,0.607327918620286
Synlett,Novel Palladium-Free Synthesis of a Key Quinazolinap Precursor,All articles of this category (opens in new window),10.1055/s-0030-1259507,2011-01-25,0.6073278034547164
European Journal of Organic Chemistry,Stereoselective Total Synthesis of the Marine Macrolide Sanctolide A,"Abstract The stereoselective total synthesis of sanctolide A, a 14‐membered polyketide‐nonribosomal peptide (PK‐NRP) hybrid macrolide, was accomplished. Sanctolide A contains a rare N ‐methyl enamide and 2‐hydroxyisovaleric acid functionality embedded into the macrocycle. The synthesis relied on Yamaguchi esterification and intramolecular dehydrative cyclization reactions to construct the core skeleton of the macrolide. The two key chiral centers were generated by Maruoka's allylation and Noyori's asymmetric ketone reduction reactions. Commercially available, inexpensive 2‐hydroxyisovaleric acid and hexanaldehyde were utilized as the raw materials for the total synthesis.",10.1002/ejoc.201500677,2015-08-06,0.6073247727597948
Journal of Organic Chemistry,"A Chiron Approach to Diversity-Oriented Synthesis of Aminocyclitols, (−)-Conduramine F-4 and Polyhydroxyaminoazepanes from a Common Precursor","The total syntheses of aminocyclitols, (−)-conduramine F-4, and polyhydroxyaminoazepanes have been achieved from a common precursor derived from tri- O -benzyl- d -glucal through a ‘diversity-oriented’ approach. Tri- O -benzyl- d -glucal was converted into a protected 1,6-diol through a sequence of steps that include transformation to a 2-tosylamidoglucose derivative, selective deprotection of primary C-6 benzyloxy group, LiAlH 4 -mediated one-step reduction of acetate groups, and reductive ring opening of the resulting hemiacetal as the key steps. The 1,6-diol served as a common precursor in our diversity oriented approach toward the target molecules. Mesylation of the diol followed by double nucleophilic substitution reaction with primary amines led to the synthesis of amino-substituted polyhydroxyazepanes. On the other hand, dialdehyde obtained from the oxidation of 1,6-diol was found to be a convenient starting material for the synthesis of aminocyclitols and (−)-conduramine F-4. McMurry coupling of the dialdehyde was successfully employed, for the first time, to construct the carbocyclic framework of aminoyclitols, while bis-Wittig olefination of the dialdehyde followed by Grubb’s(II)-catalyzed RCM delivered (−)-conduramine F-4. The stereochemistry of newly created chiral centers in aminocyclitols was established through single crystal X-ray crystallography and detailed NOE studies.",10.1021/acs.joc.6b01790,2016-11-02,0.6073086731090477
Journal of Organic Chemistry,"Total Synthesis of Allocyathin B<sub>2</sub>, a Metabolite of Bird's Nest Fungi","Allocyathin B 2 has been synthesized using aldol reactions for construction of rings A and B, introduction of the side chain for ring B, cyclization of the acetyl group into a lactone, and construction of the seven-membered diene aldehyde during the last step.",10.1021/jo971514s,1998-01-01,0.6073067865335591
European Journal of Organic Chemistry,An Approach Toward the Bridged 14‐Membered Carbon Macrocycle of Bielschowskysin,"Relying on our previous achievements toward the a total synthesis of bielschowskysin,1-5 we herein report additional efforts to close the bridged tetradecane carbocyclic core of this marine diterpene. The key step of this strategy is an intramolecular alkylation between a cis-substituted vinyl halide and a lactone that were accessed by a diastereoselective propargylation/hydrogenation sequence and palladium-catalyzed carbonylation, respectively.",10.1002/ejoc.201600271,2016-05-23,0.6072928428199531
Tetrahedron,Synthesis of new bi-2H-azirin-3-yl compounds from diazides,,10.1016/s0040-4039(00)95010-x,1985-01-01,0.6072923494489039
Tetrahedron,A novel “linch-pin” construction of dihydrojasmone a high yield synthesis of cis-jasmone,,10.1016/s0040-4039(01)86893-3,1973-01-01,0.607287472578329
Synthesis,Equilibrium Control in Bromomethylation: An Expedient Route to 2-Amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic Acid (AMPA),All articles of this category The excitatory amino acid 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA) has been prepared in gram quantities in 42% total yield by a three-step procedure from 3-hydroxy-5-methylisoxazole. It is shown how bromomethylation may be optimized through control of the involved equilibria and how N -protecting methoxymethyl groups can be removed.,10.1055/s-1993-25956,1993-01-01,0.6072845435499034
Tetrahedron,"Cyclization of 1,4-dihydroxyanthraquinone with α,β-unsaturated aldehyde: a new strategy for the synthesis of cyclopentanoids",,10.1016/j.tetlet.2015.04.016,2015-04-11,0.6072838599127495
Synlett,Nef Reaction of Nitropyrrolidines: Novel Synthesis of Hydroxypyrrolidine Derivatives,A general synthetic route to hydroxypyrrolidine derivatives using the first Nef reaction of nitropyrrolidines with chromium(II) chloride as a key step is presented.,10.1055/s-2007-985583,2007-09-01,0.6072713909018186
Angewandte Chemie International Edition,Total Synthesis of α‐ and β‐Amanitin,"α-Amanitin and related amatoxins have been studied for more than six decades mostly by isolation from death cap mushrooms. The total synthesis, however, remained challenging due to unique structural features. α-Amanitin is a potent inhibitor of RNA polymerase II. Interrupting the basic transcription processes of eukaryotes leads to apoptosis of the cell. This unique mechanism makes the toxin an ideal payload for antibody-drug conjugates (ADCs). Only microgram quantities of toxins, when delivered selectively to tumor sites through conjugation to antibodies, are sufficient to eliminate malignant tumor cells of almost every origin. By solving the stereoselective access to dihydroxyisoleucine, a photochemical synthesis of the tryptathion precursor, solid-phase peptide synthesis, and macrolactamization we obtained a scalable synthetic route towards synthetic α-amanitin. This makes α-amanitin and derivatives now accessible for the development of new ADCs.",10.1002/anie.201914935,2020-02-24,0.6072701360898285
Journal of Organic Chemistry,"Asymmetric Total Synthesis of (−)-Spirochensilide A, Part 2: The Final Phase and Completion","The final phase of the total synthesis of (−)-spirochensilide A is described. A tungsten-mediated cyclopropene-based Pauson–Khand reaction was developed to form the spiral CD ring system with desired stereochemistry at the C13 quaternary center. Other important steps enabling completion of this synthesis included an intermolecular aldol condensation to link the ABCD core with the EF fragment and a Cu-mediated 1,4-addition to stereoselectively install the C21 stereogenic center. The chemistry developed for this total synthesis of (−)-spirochensilide A ( 1 ) will aid the synthesis of polycyclic natural products bearing this unique spiral ring system.",10.1021/acs.joc.0c02510,2021-01-22,0.6072566233965466
Angewandte Chemie International Edition,Divergent Asymmetric Total Synthesis of (−)‐Voacafricines A and B,"A divergent asymmetric total synthesis of voacafricines A and B, hexacyclic monoterpene indole alkaloids, has been accomplished featuring the following key steps: a) a catalyst-controlled asymmetric Pictet-Spengler reaction of 6-methoxytryptamine with a chiral α-ketoester affording a 1,1-disubstituted tetrahydro-β-carboline in excellent yield and diastereoselectivity; b) oxidative cleavage of a 3,5-disubstituted cyclopentene furnishing a dialdehyde intermediate, which was effectively differentiated through spontaneous cyclization with the neighboring hydroxy and secondary amine functions; c) intramolecular nucleophilic addition of a tertiary amino nitrogen atom to the in situ generated oxonium species generating stereoselectively an unprecedented 8-alkyl octahydro-2H-5,8-methanofuro[2,3-b]azepin-8-ium motif bearing five contiguous stereocenters. The synthesis confirmed the absolute configuration of these two natural products.",10.1002/anie.202301517,2023-02-24,0.6072479609218225
Organic Process Research & Development,Design and Scale-Up of a Practical Enantioselective Route to 5-Phenylbicyclo[2.2.2]oct-5-en-2-one,"A practical enantioselective route to chiral 5-phenylbicyclo[2.2.2]oct-5-en-2-one 1 has been designed and developed. The target compound has been obtained as colorless crystals in 22% yield from 2-cyclohexenone, with an enantiomeric ratio higher than 99.5:0.5 and notably high chemical purity (> 99%). Three intermediates out of nine chemical steps are isolated. It is noteworthy that this process is devoid of any chromatography or distillation although all but one intermediate are oils. Key to success was the optimization of an intramolecular aldol reaction of an in situ prepared ketone aldehyde leading to the solid intermediate (1 R,4 R,4 S,6 S )-6-hydroxybicyclo[2.2.2]octan-2-one 9a that is isolated in very high chemical and chiral purity. This is an example of an intramolecular crystallization-induced diastereomer transformation (CIDT). The dehydration of this secondary alcohol to 1 required an extensive screen of reaction conditions to secure an excellent purity, essential for crystallization of this low-melting compound. The final process is simple and concentrated as demonstrated by an expeditious synthesis of 1 kg of 1 in a 30-L reactor in 10 working days.",10.1021/op200305y,2011-12-16,0.6072473855556945
Synthesis,Simple and Efficient Procedure for a Multigram Synthesis of Both trans- and cis-1-Amino-2-(trifluoromethyl)cyclopropane-1-carboxylic Acid,"A simple and efficient procedure for the multigram synthesis of both (±)-trans- and (±)-cis-1-amino-2-(trifluoromethyl)cyclopropane-1-carboxylic acid was developed. The key step of the synthesis is the addition of 1-diazo-2,2,2-trifluoroethane to methyl 2-[(tert-butoxycarbonyl)amino]acrylate, followed by thermal decomposition of the resulting pyrazoline. Gram quantities of trans- and cis-1-amino-2-(trifluoromethyl)cyclopropane-1-carboxylic acid were easily prepared from l-serine in one synthetic run.",10.1055/s-0029-1217141,2009-11-20,0.607247190366807
Tetrahedron,Synthesis of 3-aminoalkyl substituted carbapenems via a phosphorane intermediate,,10.1016/s0040-4039(00)94906-2,1985-01-01,0.6072404999154526
Angewandte Chemie International Edition,Catalytic Asymmetric Dihydroxylation of Enamides and Application to the Total Synthesis of (+)‐Tanikolide,"Asymmetric dihydroxylation of β,β′- disubstituted enamides afforded chiral tertiary-alcohol-containing α-hydroxyaldehydes and 1,2-diols with high enantioselectivity (see scheme). This method was applied to the total synthesis of the antifungal natural product (+)-tanikolide, as well as the synthesis of an intermediate en route to (S)-oxybutynin.",10.1002/anie.201004328,2010-09-30,0.6072359301271865
Angewandte Chemie International Edition,Total Synthesis of (±)‐Quadrangularin A,"The key to successful coupling in the synthesis of (±)-quadrangularin A (1) was the introduction of tert-butyl groups in the precursor to block two reactive positions. Thus, the oxidative coupling of 3,5-di-(tert-butyl)resveratrol was carried out regioselectively in an efficient total synthesis of the natural product.",10.1002/anie.200603097,2006-10-19,0.6072354555266622
Tetrahedron,Efficient synthesis of a 7-azabicyclo[2.2.1]heptane based GlyT1 uptake inhibitor,,10.1016/j.tetlet.2010.10.079,2010-10-26,0.6072329605292162
Tetrahedron,"A practical synthesis of new S,N-disubstituted derivatives of 5-(4-methylpiperidino)methyl-2-thiouracil",,10.1016/j.tetlet.2008.06.079,2008-06-23,0.6072281840928608
Organic Letters,A Next Generation Synthesis of BACE1 Inhibitor Verubecestat (MK-8931),"The development of a commercial manufacturing route to verubecestat (MK-8931) is described, highlights of which include the application of a continuous processing step to outcompete fast proton transfer in a Mannich-type ketimine addition, a copper-catalyzed amidation reaction, and an optimized guanidinylation procedure to form the key iminothiadiazine dioxide core.",10.1021/acs.orglett.8b00259,2018-02-26,0.6072181264680246
Angewandte Chemie International Edition,Enantioselective Synthesis of (+)‐Mitomycin K by a Palladium‐Catalyzed Oxidative Tandem Cyclization,"The mitomycins, a family of bioactive natural products, feature a compact 6/5/5-fused polycyclic ring structure densely decorated with highly reactive and/or fragile quinone, amino ketal, and aziridine as well as carbamate moieties. It is this striking feature that has defeated numerous synthetic attempts towards these apparently small molecules, rendering them one of the most formidable targets for total synthesis. We herein report the first enantioselective synthesis of (+)-mitomycin K, a representative of G series mitomycins. The key step of this synthesis is an enantioselective oxidative cyclization catalyzed by a palladium/(+)-sparteine system that had previously been developed by our group. The robustness of this method bodes well for further applications in the asymmetric total synthesis of natural products, particularly those with characteristic 6/5/5-fused pyrroloindole skeletons.",10.1002/anie.201701895,2017-04-20,0.607196366274325
Synlett,Langlois Reagent Mediated Tandem Cyclization of o-Hydroxyaryl Enaminones for the Synthesis of 3-(Trifluoromethyl)chromones,"Abstract An efficient and simple synthesis of various 3-(trifluoromethyl)chromones from enamino ketones is described. The key step in the synthesis involves the introduction of a trifluoromethyl (CF3) moiety onto a chromone structure. The significant features of this method include simple operational procedures, the high purity and yield of the product, and excellent regioselectivity.",10.1055/a-1906-3382,2022-07-21,0.6071944886568262
Tetrahedron,"Synthesis of the potassium salt of 2,3,4,5-tetrahydrodipicolinic acid, a key intermediate in the diaminopimelate pathway to L-lysine",,10.1016/s0040-4039(00)79065-4,1992-05-01,0.6071923680254372
Journal of Organic Chemistry,Formal Total Synthesis of (±)-γ-Lycorane and (±)-1-Deoxylycorine Using the [4+2]-Cycloaddition/Rearrangement Cascade of Furanyl Carbamates,"The total syntheses of gamma-lycorane and (+/-)-1-deoxylycorine were accomplished using an intramolecular Diels-Alder cycloaddition of a furanyl carbamate as the key step. The initially formed [4+2]-cycloadduct undergoes nitrogen-assisted ring opening followed by deprotonation/reprotonation of the resulting zwitterion to give a rearranged hexahydroindolinone. The stereochemical outcome of the IMDAF cycloaddition has the side arm of the tethered alkenyl group oriented syn with respect to the oxygen bridge. The key intermediate used in both syntheses corresponds to hexahydroindolinone 20. Removal of the t-Boc group in 20 followed by reaction with 6-iodobenzo[1,3]dioxole-5-carbonyl chloride afforded enamide 22. Treatment of this compound with Pd(OAc)(2) employing the Jeffrey modification of the Heck reaction provided the galanthan tetracycle 24 in good yield. Compound 24 was subsequently converted into (+/-)-gamma-lycorane using a four-step procedure to establish the cis-B,C-ring junction. A radical-based cyclization of the related enamide 33 was used for the synthesis of 1-deoxylycorine. Heating a benzene solution of 33 with AIBN and n-Bu(3)SnH at reflux gave the tetracyclic compound 38 possessing the requisite trans fusion between rings B and C in good yield. After hydrolysis and oxidation of 38 to 40, an oxidative decarboxylation reaction was used to provide the C(2)(-)C(3)(-)C(12) allylic alcohol unit characteristic of the lycorine alkaloids. The resulting enone was eventually transformed into (+/-)-1-deoxylycorine via known synthetic intermediates.",10.1021/jo0014109,2001-02-13,0.6071777108442926
Journal of Organic Chemistry,A Novel Strategy to Assemble the β-Diketo Acid Pharmacophore of HIV Integrase Inhibitors on Purine Nucleobase Scaffolds,"Claisen condensation, the key step in constructing the pharmacophore of aryl beta-diketo acids (DKA) as integrase inhibitors, fails in certain cases of highly electron-deficient heterocycles such as purines. A general synthetic strategy to assemble the DKA motif on the purine scaffold has been accomplished. The synthetic sequence entails a palladium-catalyzed cross-coupling, a C-acylation involving a tandem addition/elimination reaction, and a novel ferric ion-catalyzed selective hydrolysis of an enolic ether in the presence of a carboxylic acid ester.",10.1021/jo701336r,2007-10-01,0.6071759378510971
Organic Letters,An Efficient High-Yield Synthesis of <scp>d</scp>-<i>r</i><i>ibo</i>-Phytosphingosine,"[Structure: see text] [4R-[4alpha(S),5alpha]]-2,2-Dimethyl-4-(2-oxo-5-vinyl[1,3]dioxolan-4-yl)oxazolidine-3-carboxylic acid tert-butyl ester 5a, obtained in excellent yield and diastereoselectivity by the alpha-hydroxyallylation of the Garner aldehyde (4), is exploited in a novel high-yield synthesis of D-ribo-phytosphingosine (8), using microwave-enhanced cross metathesis as the key step in the chain elongation.",10.1021/ol0612096,2006-06-21,0.6071625367664631
Journal of Organic Chemistry,A Symmetry-Based Formal Synthesis of Zaragozic Acid A,"A symmetry-based strategy for the synthesis of the zaragozic acids is reported. Two enantioselective dihydroxylations were used to establish the absolute configuration of a C(2) symmetric intermediate. Noteworthy transformations include a group-selective lactonization, which accomplished an end-differentiation of a pseudo-C(2) symmetric intermediate. Late stage protecting group adjustments and oxidations accomplished a formal synthesis of zaragozic acid A.",10.1021/jo000665j,2000-08-18,0.6071606289819734
Tetrahedron,Synthetic indole alkaloids.II. A two step synthesis of 4-carbethoxy-3-ethylenedioxybutyraldehyde; a pentacyclic alkaloid precursor,,10.1016/s0040-4039(01)93543-9,1979-01-01,0.6071534805060104
Organic Letters,Total Synthesis of the Marine Alkaloid (±)-Lepadiformine via a Radical Carboazidation,"[reaction: see text] The total synthesis of lepadiformine has been achieved in 10 steps and 15% overall yield from cyclohexanone. The amino-substituted quaternary carbon center is created through a radical carboazidation reaction. The tricyclic core of lepadiformine is built via an efficient hydrogenation process, involving reduction of the azide and intramolecular reductive amination of a ketone, followed by lactamization of the intermediate gamma-aminoester. The hydroxymethyl side chain is introduced according to a modified Takahata procedure after conversion of the lactam into a thiolactam.",10.1021/ol060083+,2006-03-17,0.6071504505329075
Tetrahedron,Asymmetric synthesis of (+)-phosphinothricin and (+)-2-amino-4-phosphonobutyric acid,,10.1016/s0040-4039(01)91546-1,1984-01-01,0.6071477472565183
Tetrahedron,"The first asymmetric synthesis of (2S)- and (2R)-amino-3,3-dimethoxypropanoic acid",,10.1016/s0040-4039(02)00269-1,2002-03-01,0.6071477472565183
Organic Letters,Stereoselective Syntheses of the C‘D‘E‘F‘-Ring System of Maitotoxin and the FG-Ring System of Gambierol,"[structure: see text]. The stereoselective syntheses of the C'D'E'F'-ring system of maitotoxin and the FG-ring system of gambierol were accomplished. The key steps involve 6-endo-cyclization of methylepoxide, SmI2-induced reductive cyclization, 6-endo-cyclization of vinylepoxide, and formation of the lactone ring.",10.1021/ol016355k,2001-07-21,0.6071376896292687
Organic Letters,Short and Straightforward Synthesis of (−)-1-Deoxygalactonojirimycin,The mildness and low basicity of vinylzinc species functioning as a nucleophile in addition to alpha-chiral aldehydes is characterized by lack of epimerization of the vulnerable stereogenic center. This is demonstrated by a highly diastereoselective synthesis of 1-deoxygalactonojirimycin in eight steps from commercial starting materials with overall yield of 35%.,10.1021/ol100037c,2010-02-19,0.6071366941918207
Organic Letters,Total Synthesis of (−)-Lepadiformine A via Radical Translocation–Cyclization Reaction,"Total synthesis of (-)-lepadiformine A featuring construction of the 1-azaspiro[4.5]decane skeleton by a highly diastereoselective radical translocation-cyclization reaction of a γ-lactam derivative bearing a chiral butenolide moiety is described. The enantioselective construction of butenolide is conducted via Krische's catalytic asymmetric allylation protocol. After the radical translocation-cyclization reaction, a hydroxymethyl group at the C-13 position was stereoselectively introduced by a one-pot partial reduction-allylation protocol of the unprotected lactam derivative. Finally, the total synthesis is completed by formation of a C ring.",10.1021/acs.orglett.0c00474,2020-03-17,0.6071346860406343
Organic Letters,Synthesis of the Fully Glycosylated Cyclohexenone Core of Lomaiviticin A,"We describe two four-step sequences for conversion of the inexpensive reagent ethyl sorbate to either O-allyl-N,N-dimethyl-D-pyrrolosamine or O-allyl-L-oleandrose, protected forms of the 2,6-dideoxy sugar residues found in the complex bacterial metabolite lomaiviticin A. We also report a gram-scale synthesis of the highly-oxygenated cyclohexenone ring of this metabolite, and show this may be coupled with the aforementioned donors to form the bis(glycoside) 6. The longest linear sequence to 6 is nine steps.",10.1021/ol901710b,2009-08-31,0.6071344884942543
Angewandte Chemie International Edition,Nature‐Inspired Stereospecific Total Synthesis of <i>P</i>‐(+)‐Dispegatrine and Four Other Monomeric <i>Sarpagine</i> Indole Alkaloids,All five: The first total synthesis of the C2-symmetric indole alkaloid 1 involved a late-stage thallium(III) acetate-mediated intermolecular oxidative coupling to construct the C9C9′ bond with complete regio- and stereocontrol. The formation of a single atropodiastereomer in this critical step arises from internal asymmetric induction. The first total synthesis of four other monomeric sarpagine indole alkaloids is also described.,10.1002/anie.201206015,2012-10-16,0.6071321680838003
Organic Process Research & Development,Improved One-Pot Synthesis of Citalopram Diol and Its Conversion to Citalopram,"An improved process is developed for the preparation of citalopram diol, 2 which involves two consecutive Grignard reactions in situ followed by an efficient and simple workup process with improved overall yield. Process development efforts for conversion of 2 into citalopram, 1, and a control strategy for impurities are discussed. The present work addresses the challenges associated with the process development and scale-up of citalopram such as handling of unstable intermediates, control of various potential impurities, and process safety to achieve an economic and scalable process.",10.1021/op3002596,2013-04-22,0.6071271417931949
Journal of Organic Chemistry,A New Stereoselective Synthesis of (−)-Isoavenaciolide and (−)-Avenaciolide,"The synthesis of isoavenaciolide and avenaciolide in their natural enantiomeric forms are described. In both syntheses, α-(phenylthio)-β-[(methoxycarbonyl)methyl]-γ-lactones obtained by the base-induced cyclization of enantiomerically enriched γ-[(phenylthio)acyl] α,β-unsaturated esters were used as starting materials. In the isoavenaciolide synthesis the key step is the stereoselective hydroxylation of the enolate generated in the (methoxycarbonyl)methyl chain that permits the bis-lactonization by a double transesterification. The configuration in the quaternary center vicinal to the carbonyl group in the ring was critical in order to obtain successfully the α-methylene lactone. In avenaciolide, the stereoselective synthesis of the bis-lactone unit was performed taking advantage of the presence of the phenyl sulfide group which by previous activation was used as leaving group to obtain the fused ring by an intramolecular substitution utilizing the carboxylate of the β-substituent as nucleophile. In this case, the α-methylene lactone was obtained by previously reported methodology.",10.1021/jo9611935,1996-01-01,0.6071243026641484
Synlett,"A Formal Total Synthesis ofEleman-8β,12-olide with SmI<sub>2</sub>-Induced Cyclization","The formal total synthesis of elemane-type sesquiterpenoid eleman-8β,12-olide was conducted with samarium(II) iodide-induced cyclization as the key step.",10.1055/s-2003-38374,2003-01-01,0.6071151002427359
Organic Letters,A Simple Route toward the Synthesis of Bisbenzothiadiazole Derivatives,"A simple and efficient route toward the synthesis of 4,4'-bis(2,1,3-benzothiadiazole) and 7,7'-dibromo-4,4'-bis(2,1,3-benzothiadiazole) has been developed. Oligomers were synthesized with bisbenzothiadiazole units either at the periphery or core, and each oligomer was characterized by X-ray crystallography. Both crystal structures display supramolecular interactions between the conjugated backbones, although the former, bearing two bisbenzothiadiazole units, has extended interactions within layers that engage all of the thiadiazole rings.",10.1021/ol8022837,2008-11-13,0.6070936682301287
Tetrahedron,Pyrocine synthesis - a new approach to chrysanthemic ester,,10.1016/s0040-4039(01)94686-6,1978-01-01,0.6070936132257685
Journal of Organic Chemistry,Synthesis of Chiral Pilocarpine Analogues via a C-8 Ketone Intermediate,The synthesis of a chiral pilocarpine analogue 3 in which the lactone ring is replaced by an oxazolidinone and the bridging methylene group is in the ketone oxidation state has been accomplished. The utility of this compound as a key intermediate for the preparation of more complex structures was demonstrated by its reduction to two alcohol epimers and its reaction with a methylene ylide.,10.1021/jo0111210,2002-07-26,0.6070915340856494
Synlett,"Molecular Complexity from Aromatics - AnEfficient Route to 1,8-Dimethyl-5-spirocyclopropanetricyclo[6.3.0.0<sup>²,6</sup>]undec-10-one:A Potential Intermediate for Synthesis of Ceratopicanol",A new stereoselective synthesis of linearly fused triquinane intermediate from a simple aromatic precursor is described. Cycloaddition of cycloliexa-2.4-dienone and photochemical oxa-di-pi-methane rearrangement in a functionalized tricycloundecenone are the key features of our methodology.,10.1055/s-2008-1078592,2008-07-15,0.6070830705735755
Journal of Organic Chemistry,Improved Enantioselective Synthesis of (<b>−</b>)-Linderol A: Hindered Rotation about Aryl−Csp<sup>3</sup> Bond,"An improved enantioselective total synthesis of (-)-linderol A has been achieved via a five-step reaction with a 21% overall yield, starting from phloroacetophenone and (-)-alpha-phellandrene, two commercially available reagents. In the diastereoselective epoxidation step, the analysis of the two endocyclic epoxide intermediates reveals a hindered sp(2)-sp(3) rotation, which results in rotational diastereoisomers.",10.1021/jo902567y,2010-03-24,0.6070787592646584
Journal of Organic Chemistry,Efficient Enantioselective Synthesis of Condensed and Aromatic-Ring-Substituted Tyrosine Derivatives,"An efficient access to both condensed and conjugated tyrosine analogues of high enantiomeric purity is described. Novel ring-substituted tyrosines were synthesized by Suzuki cross couplings of appropriately protected l-3-iodotyrosine with a series of activated and deactivated boronic acid derivatives to achieve the target compounds in high yields. d- and l-4-hydroxy-1-naphthylalanines were readily prepared from the corresponding alpha-enamide in two different approaches, by asymmetric hydrogenation as well as by unselective hydrogenation and enzymatic resolution of the racemic mixture.",10.1021/jo060704c,2006-06-22,0.6070779392373292
Organic Letters,Bioinspired Total Synthesis of Gymnothelignan N,"Bioinspired total synthesis of gymnothelignan N was accomplished in 13 steps and 6.7% overall yield. The synthesis features a syn Evans aldol reaction, an intramolecular hydrogenative dehydration reaction, and a phenol oxidative dearomatization/Friedel-Crafts reaction, which provides a new plausible biosynthetic pathway for the gymnothelignans and other symbiotic members. Meanwhile, another tetrahydrofuran-type lignan beilschmin A was also synthesized.",10.1021/ol501960j,2014-08-08,0.6070770259892121
Organic Letters,Synthesis of Plakortolides E and I Enabled by Base Metal Catalysis,"A protecting-group-free synthesis of two endoperoxide natural products, plakortolide E and plakortolide I, is reported. Key steps are a vanadium-mediated epoxidation, an iron-catalyzed allylic substitution, and a cobalt-induced endoperoxide formation. Our approach combines chemoselective bond-forming reactions and one-pot operations to forge an overall efficient synthesis.",10.1021/acs.orglett.1c01457,2021-06-07,0.6070726032187227
Journal of Organic Chemistry,Synthesis of the C14−C25 Subunit of Bafilomycin A<sub>1</sub>,"The enantioselective synthesis of the C14-C25 subunit of bafilomycin A1 was realized in a convergent route. The sequence involves two dynamic kinetic resolution steps of 2-alkyl 1,3-diketones that use optically active ruthenium complexes, an anti-selective reduction of a beta-hydroxyketone to control the C23 stereogenic center, and an aldol-type reaction under Evans' conditions, which sets the C17 and C18 stereogenic centers.",10.1021/jo035068m,2003-11-20,0.6070683059566109
Tetrahedron,A practical strategy for the synthesis of 2-dialkylamino-4-arylamino-6-aminopyrimidines,,10.1016/j.tetlet.2009.07.154,2009-08-07,0.6070619866317828
European Journal of Organic Chemistry,Synthesis of Sphingosine‐1‐phosphonate and Homosphingosine‐1‐phosphonate,"Abstract In the first approach to homosphingosine‐1‐phosphonate, D ‐glucofuranose was selectively deoxygenated at C‐5. Bond cleavage between C‐1 and C‐2 afforded a 5‐deoxy‐ D ‐ threo ‐pentose intermediate. ( E )‐Selective Wittig reaction with a C 14 ‐chain gave a C 19 ‐intermediate, which was readily transformed into homosphingosine. Formation of a cyclic urethane containing the 3‐amino and the 4‐hydroxy group of the C 19 ‐intermediate permitted regioselective introduction of the phosphonate group at C‐1, thus affording the target molecule after deprotection. In a second and shorter route, C 18 ‐sphingosine was converted to a cyclic urethane containing the 2‐amino and the 3‐hydroxy group of the C 18 ‐chain. C 1 ‐Chain extension by a hydroxymethyl group by introduction of cyanide led to the same C 19 cyclic urethane as obtained in the first route. Similarly, the C 18 cyclic urethane led to the other target molecule, namely sphingosine‐1‐phosphonate. The third and shortest route to homosphingosine‐1‐phosphonate could be based on regioselective 1‐ O ‐tosylation of 1,2,3‐(trihydroxy)octadec‐4‐ene. Transformation into a 1,2‐epoxide, then combination of C 1 ‐chain extension and introduction of a phosphonate group with methylphosphonate as reagent, and finally azide introduction, led after functional group liberation to the target molecule. As shown, also truncated derivatives are readily accessible by this route. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2005)",10.1002/ejoc.200400671,2005-03-01,0.6070595014620097
Synthesis,An Expeditious Synthesis of 8-Methoxy-1-tetralone,"8-Methoxy-1-tetralone was synthesized in a concise and efficient manner involving a sequential palladium-mediated cross-coupling reaction (Heck), catalytic hydrogenation, and intramolecular acylation mediated by Eaton’s reagent or Lewis acids. The pivotal step in the synthesis was the use of a bromine substituent at the benzenoid C4 position of the intermediate methyl 4-arylbutyric ester to ensure cyclization ortho to the methoxy moiety and obviate cyclization at the para position to the thermodynamically preferred 6-methoxy-1-tetralone, the sole product obtained in the absence of this blocking group.",10.1055/s-0035-1561601,2016-04-20,0.6070389210266033
Organic Letters,“One-Pot” Reductive Lactone Alkylation Provides a Concise Asymmetric Synthesis of Chiral Isoprenoid Targets,"An efficient method, based on nucleophilic addition to lactones followed by modified in situ Clemmensen reduction, provides a short synthetic route to chiral isoprenoid targets. The efficacy of this method has been exemplified through the synthesis of several targets including the commercial fragrance Rosaphen, the side chain of Zaragozic acid C, the cotton leaf sex pheromone, and the side chains of vitamin E.",10.1021/ol401801g,2013-08-19,0.607036295955784
Organic Letters,Alkaloid Synthesis Using Chiral δ-Amino β-Ketoesters:  A Stereoselective Synthesis of (−)-Lasubine II,"[reaction: see text]A highly stereoselective asymmetric synthesis of the quinolizidinealkaloid (-)-lasubine II from a delta-amino beta-hydroxy ketone, a new polyfunctionalized chiral building block, is described.",10.1021/ol0061438,2000-08-01,0.607032122912941
Organic Letters,Stereoselective Synthesis of the Rocaglamide Skeleton via a Silyl Vinylketene Formation/[4 + 1] Annulation Sequence,The tricyclic core of the cyclopentabenzofurans has been prepared in an efficient and stereoselective manner utilizing an intramolecular silyl vinylketene formation/[4 + 1] annulation sequence. This novel approach affords the ABC ring system where the adjacent phenyl and aryl substituents of the C ring have the required cis relationship.,10.1021/ol801435j,2008-08-28,0.6070251467707471
Journal of Organic Chemistry,"Synthesis of Chromone, Quinolone, and Benzoxazinone Sulfonamide Nucleosides as Conformationally Constrained Inhibitors of Adenylating Enzymes Required for Siderophore Biosynthesis","MbtA catalyzes the first committed step of mycobactin biosynthesis in Mycobacterium tuberculosis (Mtb) and is responsible for the incorporation of salicylic acid into the mycobactin siderophores. 5'-O-[N-(Salicyl)sulfamoyl]adenosine (Sal-AMS) is an extremely potent nucleoside inhibitor of MbtA that possesses excellent activity against whole-cell Mtb but suffers from poor bioavailability. In an effort to improve the bioavailability, we have designed four conformationally constrained analogues of Sal-AMS that remove two rotatable bonds and the ionized sulfamate group on the basis of computational and structural studies. Herein we describe the synthesis, biochemical, and microbiological evaluation of chromone-, quinolone-, and benzoxazinone-3-sulfonamide derivatives of Sal-AMS. We developed new chemistry to assemble these three heterocycles from common β-ketosulfonamide intermediates. The synthesis of the chromone- and quinolone-3-sulfonamide intermediates features formylation of a β-ketosulfonamide employing dimethylformamide dimethyl acetal to afford an enaminone that can react intramolecularly with a phenol or intermolecularly with a primary amine via addition-elimination reaction(s). The benzoxazinone-3-sulfonamide was prepared by nitrosation of a β-ketosulfonamide followed by intramolecular nucleophilic aromatic substitution. Mitsunobu coupling of these bicyclic sulfonamides with a protected adenosine derivative followed by global deprotection provides a concise synthesis of the respective inhibitors.",10.1021/jo400976f,2013-06-27,0.6070233215101084
Journal of the American Chemical Society,Total Synthesis of (±)-Crokonoid A,"We report herein a total synthesis of crokonoid A, featuring a dually bridged 6/7/6/5-fused tetracyclic carbon framework incorporating an unprecedented tricyclo[4.4.1.1 1,4 ]dodecane-2,11-dione core. The synthesis is highlighted by the following key transformations: (a) a regioselective decarboxylative allylation of a 1,3-dienyl carbonate to furnish an α-allyl-β,γ-unsaturated ketone; (b) a domino sequence involving ozonolysis, intramolecular aldol reaction, and acetalization to construct the bicyclo[4.3.1]decanedione core from a fused ring system, in which the acetalization step effectively stabilized the otherwise unstable aldol intermediate; (c) a palladium-catalyzed intramolecular cycloalkenylation of a ketone to assemble the bicyclo[3.2.1]octanedione system, in which the hybridization state of the neighboring carbon proved crucial for the success of this cyclization; and (d) SmI 2 –HMPA-mediated regio- and stereoselective reduction of the C14 ketone.",10.1021/jacs.5c14479,2025-09-26,0.6070201319165416
Synthesis,A Convenient Route to 3-Pyrroline Utilizing the Delépine Reaction,"All articles of this category 3-Pyrroline(2,5-dihydro-1 H -pyrrole) has been prepared from (Z)-1, 4-dichloro-2-butene ( 1 ) in three steps in an overall yield of 74%.",10.1055/s-1988-27571,1988-01-01,0.6070165918356327
Angewandte Chemie International Edition,Total Synthesis of Liangshanone,"The first total synthesis of liangshanone, a hexacyclic ent-kaurane diterpenoid alkaloid, has been completed. Its intricate cagelike framework was assembled through several key transformations, including an oxidative dearomatization/Diels-Alder (OD/DA) cycloaddition sequence, a tandem alkene cleavage/Mannich cyclization, a Robinson-type annulation, and an intramolecular aldol reaction. Notably, an organocatalytic enantioselective α-hydroxymethylation process allowed the preparation of an enantiomerically enriched tricyclic intermediate that should enable asymmetric access to the target natural product.",10.1002/anie.202011923,2020-09-17,0.6070056071169803
Organic Letters,Diastereoselective Nitrenium Ion-Mediated Cyclofunctionalization: Total Synthesis of (+)-Castanospermine,"The asymmetric total synthesis of the α-glucosidase inhibitor (+)-castanospermine is reported. The central theme in our approach to this polyhydroxylated alkaloid is the simultaneous generation of the piperidine ring and the C-1/8a erythro stereodiad through the diastereoselective, oxamidation of an unsaturated O-alkyl hydroxamate. This process is believed to proceed sequentially via singlet acylnitrenium and aziridinium ion intermediates.",10.1021/ol102371x,2010-10-21,0.6069971843967658
Tetrahedron,A new synthesis of 12-O-methyl royleanone,,10.1016/s0040-4039(00)97848-1,1990-01-01,0.6069942239680268
Organic Letters,Synthetic Strategy for Construction of Highly Congested Tetracyclic Core (6–5–7–4) of Harziane Diterpenoids,"The structurally intriguing tetracyclic core of complex harziane diterpenoid was constructed in 14 steps from commercially available 3-ethoxycyclohex-2-en-1-one. The key steps were a Mn/Cu-mediated oxidative 1,3-dicarbonyl radical cascade cyclization reaction, which diastereoselectively formed the core of dimethylbicyclo[3.2.1]octane structure, and a Au-catalyzed diastereoselective formal [2 + 2] cycloaddition for construction of the harziane diterpenoid tetracyclic framework. The developed method paves the way for achieving total synthesis of this type of complex natural product.",10.1021/acs.orglett.1c00769,2021-05-14,0.6069848862426446
Angewandte Chemie International Edition,Bioinspired Total Synthesis of the Dimeric Indole Alkaloid (+)‐Haplophytine by Direct Coupling and Late‐Stage Oxidative Rearrangement,"Abstract A bioinspired convergent total synthesis of (+)‐haplophytine, a dimeric indole alkaloid with diazabicyclo[3.3.1]nonane and hexacyclic aspidosperma segments, is described. This synthesis involves the direct coupling of the two segments in a AgNTf 2 ‐mediated Friedel–Crafts reaction and construction of the diazabicyclo[3.3.1]nonane skeleton through late‐stage chemoselective aerobic oxidation of the 1,2‐diaminoethene moiety and a sequential semipinacol‐type rearrangement.",10.1002/anie.201609285,2016-11-07,0.6069831236865019
Journal of Organic Chemistry,Total Synthesis of (<i>S</i>)-(+)-Citreofuran by Ring Closing Alkyne Metathesis,"A concise total synthesis of citreofuran 4 is described, a structurally unique octaketide derivative belonging to the curvularin family. Key steps involve the elaboration of orsellinic acid methyl ester 5 to acid 14, which converts, on attempted formation of the corresponding acid chloride, to the 3-alkoxyisocoumarin derivative 20. This heterocycle can be used as an activated ester to give ketone 21 on treatment with 3-pentynylmagnesium bromide in the presence of TMSCl as the activating agent. Ring- closing alkyne metathesis (RCAM) of diyne 21 catalyzed by (tBuO)(3)W[triple bond]CCMe(3) affords the strained cycloalkyne 22. Treatment with acid renders its triple bond susceptible to nucleophilic attack by the adjacent carbonyl group, thus leading to a transannular cycloaromatization with formation of the intact skeleton of citreofuran. An X-ray crystallographic study reveals conformational details about this natural product. Finally, it is shown that 4 as well as its protected precursor 23 are able to cleave double-stranded DNA under oxidative conditions.",10.1021/jo026686q,2003-01-23,0.606982836412623
Journal of Organic Chemistry,Synthesis of Chrysene Derivatives via Copper-Catalyzed One-Pot Dimerization of 2-Alkynyl-1-acetylbenzenes,An efficient route for highly substituted chrysene derivatives via operationally simple copper-catalyzed one-pot dimerization of 2-alkynyl-1-acetylbenzenes is described.,10.1021/jo500182k,2014-04-18,0.6069825089528346
Journal of Organic Chemistry,A Concise Total Synthesis of (−)-Mesembrine,"A concise total synthesis of mesembrine (four steps from known compound) was achieved both racemically and asymmetrically. Two key reactions were used here. One is the Rh(I)-catalyzed [5 + 1] cycloaddition of vinylcyclopropane 3c and CO. The other one is Buchwald's Pd-catalyzed coupling reaction that coupled β,γ-cyclohexenone 2c with aryl bromide 5 (using dppe ligand for racemic or (S)-Antphos ligand for asymmetric synthesis) to give γ,γ-disubstituted α,β-cyclohexenone 1c. Finally, aza-Michael addition converted 1c to mesembrine.",10.1021/acs.joc.6b01908,2016-10-10,0.6069815097805694
Tetrahedron,Tetrabutylammonium chloride-triggered 6-endo cyclization of o-alkynylisocyanobenzenes: an efficient synthesis of 2-chloro-3-substituted quinolines,,10.1016/j.tetlet.2009.09.096,2009-09-25,0.6069813059241828
Journal of Organic Chemistry,"A Practical Total Synthesis of Hapalosin, a 12-Membered Cyclic Depsipeptide with Multidrug Resistance-Reversing Activity, by Employing Improved Segment Coupling and Macrolactonization","A practical total synthesis of hapalosin, a compound with multidrug resistance-reversing activity, has been carried out using an unprecedented macrolactonization strategy. One of the features of the new approach is the straightforward and fully stereocontrolled access to the key gamma-amino beta-hydroxy carboxylic acid subunit via an efficient acetate aldol addition reaction with N-methyl alpha-aminoaldehydes, which relies on a camphor-derived chiral lithium acetate enolate reagent. The scope of this aldol reaction is investigated and its potential application to the synthesis of other structurally related, biologically relevant compounds illustrated. Remarkably, the chiral tether in the resulting gamma-amino aldol adducts sterically protect the carbonyl group, thus avoiding intramolecular cyclization during the amino group deprotection and the subsequent segment coupling event. After successful segment coupling and smooth, clean release of the chiral auxiliary, a new macrolactonization protocol, based on the principle of double activation of both reactive sites, is applied, which leads to the 12-membered macrolactone hapalosin in unprecedented chemical efficiency.",10.1021/jo0497499,2004-05-08,0.6069753123360793
Tetrahedron,A facile route for the synthesis of limonidilactone analogues from andrographolide,,10.1016/j.tetlet.2004.10.135,2004-11-12,0.6069682812018865
Angewandte Chemie International Edition,"Total Synthesis of Candicanoside A, a Potent Antitumor Saponin with a Rearranged Steroid Side Chain","The fused-ring scaffold of candicanoside A (1), a potent antitumor agent with a unique differential pattern, has now been synthesized from inexpensive starting materials. Compound 1 has the potential to act as a lead compound for the synthesis of antitumor agents with a novel mode of action.",10.1002/anie.200604761,2007-02-20,0.606968178347372
Organic Process Research & Development,Improved “Oxazole” Method for the Practical and Efficient Preparation of Pyridoxine Hydrochloride (Vitamin B<sub>6</sub>),"Vitamin B 6, a well-studied vitamin B, has been synthesized using an oxazole method for the past 20 years. The oxazole method provided 56.2% overall yield but also generated safety, environmental, and health problems, such as using toxic benzene as solvent and unstable, corrosive, and pollutive HCl and POCl 3 as reagents. To use the same equipment but the least amount of toxic agents, we developed new reaction conditions for the early steps. For example, we successfully replaced toxic HCl/benzene conditions with NaHSO 4 /PhCH 3 conditions and also developed a novel and efficient dehydrating agent trichloroisocyanuric acid/Ph 3 P/Et 3 N to synthesize the key intermediate 5-butoxy-4-methyl oxazole, instead of using phosphorus oxychloride. These improvements resolved safety, waste avoidance, and workup issues that plagued the previous methodologies. Our process comprised six easy synthetic steps and generated vitamin B 6 with 99.4% purity in 56.4% overall yield.",10.1021/op4001687,2013-11-13,0.6069588393972734
Journal of Organic Chemistry,A Stereodivergent Approach to Substituted 4-Hydroxypiperidines,A stereodivergent route toward both diastereomeric forms of functionalized 4-hydroxypiperidines has been successfully developed. This route involves biocatalytic generation of the enantiopure starting materials followed by functionalization via N-acyliminium ion-mediated CC-bond formation.,10.1021/jo025943o,2002-09-17,0.6069541105393069
Organic Process Research & Development,Short and Scalable Synthesis of Enantiopure <i>N</i>-Boc-<i>trans</i>-4-methyl-<scp>L</scp>-prolinol,A scalable and chromatography-free synthesis of enantiopure N -Boc- trans -4-methyl- l -prolinol ( 1 ) on the multi-gram scale is described. Two shortest possible routes have been developed using commercially available and inexpensive amino acids such as 4-hydroxy- l -proline and l -pyroglutamic acid to afford 1 (>99% purity by high-performance liquid chromatography) with a moderate yield. This chiral precursor can act as a promising building block by providing practical access to a diverse array of 4-alkyl- l -prolines.,10.1021/acs.oprd.3c00053,2023-05-03,0.6069530576975986
Synthesis,"A One Pot Synthesis of 3α-Halohydrazides From α,α-Dicyano-Epoxides",All articles of this category A convenient and efficient new synthesis of α-halohydrazides from gem -dicyano expoxides is described.,10.1055/s-1987-27929,1987-01-01,0.6069510783476516
Journal of the American Chemical Society,Total Synthesis and Structural Revision of the Marine Macrolide Neopeltolide,"The total synthesis and structural revision of the marine natural product neopeltolide is reported. The key bond-forming step involves a Lewis acid-catalyzed intramolecular cyclization to install the tetrahydropyran ring and the macrocycle simultaneously. This type of cyclization is the first of its kind and assembles the carbon backbone of the natural product efficiently. The synthesis of the reported structure revealed differences in the data between the natural and synthetic material. After significant investigation, the diastereomeric molecule with the C11 and C13 configurations inverted was synthesized using the initial route. This compound matches the data reported for neopeltolide (1H, 13C, HRMS, IR, NOESY, [alpha]), thereby establishing the correct overall structure for this potent macrolide natural product, including the relative and absolute stereochemistry.",10.1021/ja710080q,2007-12-28,0.6069462887720795
Synthesis,Stereoselective Concise Total Synthesis of Leodomycin C and D,"Stereoselective concise total synthesis of leodomycin C and D from commercially available propylene oxide using Jacobsen's hydrolytic kinetic resolution (HKR), base-promoted alkyne zipper reaction, TPP-promoted enyne ester (ynoate) to diene ester (dienoate) isomerization, and (R)-(+)-2-methyl-CBS-oxazaborolidine reduction as key steps is reported.",10.1055/s-0031-1289640,2011-12-08,0.6069375219515871
Synthesis,Synthesis of a New Chiral Sulfonic Acid,"A convenient route to an original chiral sulfonic acid is disclosed. The synthesis is based on an optimized and regioselective direct bis-orthoarylation of a commercially available phenol, followed by a Newman–Kwart rearrangement. Resolution by preparative chiral HPLC and oxidative cleavage give the targeted Brønsted acid in >99% ee.",10.1055/s-0031-1290753,2012-03-28,0.6069360121146604
Synlett,Convergent Synthesis of the Putative Biogenetic Precursor of Mycaperoxide B and a Norsesterterpene Triene Isolated from an Australian sponge,"All articles of this category The synthesis of enantiomerically pure norsesterterpene triene ester 1 , extracted from an Australian marine sponge Latrunculia brevis , has been achieved by preparation of E , E -diene 3a via a Julia one-pot olefination and addition to 2,5,5,8a-tetramethyl-octahydro-naphthalen-1-one 5 . The synthesis of Z , E -diene 3b , the putative biogenetic precursor of mycaperoxide B 2 has also been achieved following the same methodology. chiral synthesis - marine norsesterterpene - mycaperoxide",10.1055/s-1999-2580,1999-02-01,0.6069244303854208
Tetrahedron,"Synthesis of a new zwitterionic cyclopentadienyl-imidazolium compound and isolation of the 3,3′-(trans-3,5-cyclopentenyl)di(1-tert-butylimidazolium)bromide intermediate",,10.1016/j.tetlet.2004.09.137,2004-10-12,0.606917189974456
Journal of Organic Chemistry,"Synthesis of [Ethylene-1-(η<sup>5</sup>-4,5,6,7-tetrahydro-1-indenyl)-2- (η<sup>5</sup>-4‘,5‘,6‘,7‘-tetrahydro-2‘-indenyl)]titanium Dichloride, the Elusive Isomer of the Brintzinger-Type<i>a</i><i>nsa</i>-Titanocenes",We present a short synthesis of 1-(2-indenyl)-2-(3-indenyl)ethane (5) and a method for its conversion to the ansa-metallocene [ethylene(eta5-inden-1-yl)(eta5-inden-2-yl)]titanium dichloride (13). The synthetic strategy applied to prepare bisindene 5 relies on the efficient alkylation of 2-(phenylsulfonyl)indane followed by HMPA-assisted E1cB-elimination of phenylsulfinate. This tandem sequence circumvents the predisposition of indene to undergo C(1)-alkylation and enables access to C(2)-substituted indenes. The key step in the synthesis of the title ansa-titanocene (4) features a previously unreported equilibration step to generate the bis(indenide anion) of 5. Complexation with TiCl4.(THF)2 followed by hydrogenation of the product metallocene furnishes ansa-titanocene 4.,10.1021/jo034975o,2003-10-01,0.6069169427292406
Synthesis,"Synthesis of Substituted 5-(3-Hydroxypropyl)pyrrolidin-2-ones and Pyrrolizidinones from Nitroethane via C3 Functionalized 5,6-Dihydro-4H-1,2-oxazines: A Novel Approach to Some Analogues of the Antidepressant Rolipram","Easily accessible [(5,6-dihydro-4H-1,2-oxazin-3-yl)methyl]malonates­ 1 were converted into substituted 5-(3-hydroxypropyl)pyrrolidin-2-ones 2 and pyrrolizidinones 3, which are versatile products and intermediates for organic and bioorganic chemistry. The synthetic sequence suggested includes stereoselective two-step reduction of an oximino fragment, followed by intramolecular cyclization involving one of the CO2Me groups and decarboxylation in the last stage. The efficiency of this strategy was demonstrated by the stereoselective synthesis of pyrrolizidinone rac-4, a highly efficient analogue of antidepressant Rolipram, from nitroethane.",10.1055/s-0029-1216806,2009-05-12,0.606913042207409
Journal of Organic Chemistry,"New, Efficient Synthesis of Oseltamivir Phosphate (Tamiflu) via Enzymatic Desymmetrization of a <i>meso</i>-1,3-Cyclohexanedicarboxylic Acid Diester","A new, enantioselective synthesis of the influenza neuraminidase inhibitor prodrug oseltamivir phosphate 1 (Tamiflu) and its enantiomer ent-1 starting from cheap, commercially available 2,6-dimethoxyphenol 10 is described. The main features of this approach comprise the cis-hydrogenation of 5-(1-ethyl-propoxy)-4,6-dimethoxy-isophthalic acid diethyl ester (6a) and the desymmetrization of the resultant all-cis meso-diesters 7a and 7b, respectively. Enzymatic hydrolysis of the meso-diester 7b with pig liver esterase afforded the (S)-monoacid 8b, which was converted into cyclohexenol 17 via a Curtius degradation and a base-catalyzed decarboxylative elimination of the Boc-protected oxazolidinone 14. Introduction of the second amino function via S(N)2 substitution of the corresponding triflate 18 with NaN3 followed by azide reduction, N-acetylation, and Boc-deprotection gave oseltamivir phosphate 1 in a total of 10 steps and an overall yield of approximately 30%. The enantiomer ent-1 was similarly obtained via an enzymatic desymmetrization of meso-diester 7a with Aspergillus oryzae lipase, providing the (R)-monoacid ent-8a.",10.1021/jo800264d,2008-06-03,0.6069125326312017
Synthesis,A Novel and Facile Two Step Synthesis of 5-Aryl-2(1<i>H</i>)-pyridones,,10.1055/s-1985-31189,1985-01-01,0.6069121711765031
European Journal of Organic Chemistry,Synthesis of Novel Angular Heterocyclic Lignans by an InCl<sub>3</sub>‐Catalyzed Friedel–Crafts‐Type Cyclization,"Abstract The synthesis of a 1‐aryltetralin privileged structure‐based library of novel angular heterocyclic lignans is described. Indolotetralins 3 , tetrahydroquinolinotetralins 4 , and thiochromanotetralins 5 were obtained from the methyl ester of thuriferic acid 2 according to a three‐step procedure involving an InCl 3 ‐catalyzed Friedel–Crafts‐type cyclization as the key step.(© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2008)",10.1002/ejoc.200701027,2008-02-18,0.6069115206812004
Synlett,A Facile One-Pot Synthesis of Polyfunctionalized 2-Unsubstituted Benzo[<i>b</i>]furans,"All articles of this category A facile one-pot synthesis of 2-unsubstituted highly functionalized benzo[b]furans is reported. The synthesis includes the coupling of an iodophenol derivative with (trimethylsilyl)acetylene, catalyzed by a Pd(0)/Cu(I) system, and a regioselective cyclizationdeprotection step mediated by TMG (1,1,3,3-tetramethylguanidine) and SiO 2 . Selective reductions then afford the dihydro analogues.",10.1055/s-1993-22663,1993-01-01,0.6069040816476893
Organic Letters,Straightforward Synthesis of (<i>S</i>)- and (<i>R</i>)-α-Trifluoromethyl Proline from Chiral Oxazolidines Derived from Ethyl Trifluoropyruvate,[Structure: see text] A concise synthesis of both enantiomers of alpha-Tfm-proline and (S)-alpha-Tfm-prolinol from ethyl trifluoropyruvate is reported. The key step is a diastereoselective allylation reaction of ethyl trifluoropyruvate and (R)-phenylglycinol-based oxazolidines or imine. The lactone obtained by cyclization of the resulting hydroxy ester proved to be a valuable intermediate for the synthesis of (S)-alpha-Tfm-allylglycine and (S)-alpha-Tfm-norvaline in enantiopure form.,10.1021/ol062593+,2006-11-30,0.606901185498398
Organic Letters,Short Total Synthesis of (−)-Kainic Acid,"A short total synthesis of (-)-kainic acid has been developed involving a novel diastereofacial differentiating Cu-catalyzed Michael addition-cyclization reaction, which provided access to a chiral pyrroline in a highly stereoselective manner. The chiral pyrroline was converted to (-)-kainic acid via the stereoselective 1,4-reduction of the pyrroline double bond in three steps.",10.1021/ol5009526,2014-04-17,0.6068962563663926
Tetrahedron,Convergent synthesis of (+)-aspergillide B via a highly diastereoselective oxocarbenium allylation,,10.1016/j.tetlet.2010.06.025,2010-06-12,0.6068942572619743
Organic Letters,Diastereoselective Formation of Tetrahydrofurans via Pd-Catalyzed Asymmetric Allylic Alkylation: Synthesis of the C13–C29 Subunit of Amphidinolide N,An efficient synthesis of the C13-C29 fragment of amphidinolide N is described. The synthesis relies on a new strategy involving Pd-catalyzed asymmetric allylic alkylation to generate diastereoselectively the cis- or trans-THF unit simply by varying the enantiomer of the ligand. The C19 hydroxyl-bearing stereocenter was introduced using a chelation-controlled allylation which led exclusively to a single diastereoisomer.,10.1021/ol302409g,2012-10-25,0.6068897999188809
Organic Letters,Pharmacophore Mapping in the Laulimalide Series:  Total Synthesis of a Vinylogue for a Late-Stage Metathesis Diversification Strategy,"An efficient synthesis of the macrocyclic core of laulimalide with a pendant vinyl group at C20 is described, allowing for late-stage introduction of various side chains through a selective and efficient cross metathesis diversification step. Representative analogues reported herein are the first to contain modifications to only the side chain dihydropyran of laulimalide and des-epoxy laulimalide. This step-economical strategy enables the rapid synthesis of new analogues using alkenes as an inexpensive, abundantly available diversification feedstock.",10.1021/ol061619u,2006-08-01,0.6068723408248358
Journal of the American Chemical Society,Total Synthesis of (+)-Manzamine A,"A novel synthetic route to (+)-manzamine A was developed. It highlights an amazingly efficient construction of a highly strained 15-membered ring across a cyclohexenone ring with the aim of installing the requisite functionalities in a completely stereocontrolled manner. Other key features include a stereoselective Diels-Alder reaction of an optically active butenolide, construction of the 15-membered ring by intramolecular Mitsunobu reaction of a nosyl amide, [3,3]-sigmatropic rearrangement of allyl cyanate for stereoselective introduction of nitrogen functionality at a sterically congested position, and a ring-closing metathesis in the presence of labile functional groups.",10.1021/ja103721s,2010-07-13,0.60687181949381
Journal of the American Chemical Society,The Total Synthesis of Lipid I,"A total synthesis of lipid I (4), a membrane-associated intermediate in the bacterial cell wall (peptidoglycan) biosynthesis pathway, is reported. This highly convergent synthesis will enable further studies on bacterial resistance mechanisms and may provide insight toward the development of new chemotherapeutic agents with novel modes of action.",10.1021/ja016082o,2001-06-29,0.6068610781257195
Synlett,The Development of Organometallic Methodologies For the Stereospecific Introduction of Cephalosporin Side Chains,"All articles of this category A variety of 3-substituted cephems has become available via the coupling of 3-trifloxycephems with organostannanes, by a modified Stille coupling procedure that includes a new palladium ligand, tri(2-furyl)phosphine. A complementary cuprate coupling via the same intermediates is also described. A cheaper alternative to the triflates are the enol fluorosulfonates, which also undergo Stille and organocuprate couplings. A radically different approach to cephaosporins from penicillins involves a modification of the Morin rearrangement that involves the intermediacy of allenylazetidinones; these undergo chemoselective addition of cuprates to the allene central carbon, followed by rapid cyclization by intramolecular sulfenylation. The process was applied, i.a. , to the efficient synthesis of the new oral antibiotic Cefprozil. 1. Introduction 2. The Stille Approach to Novel Cephalosporins 3. Other Cross-Coupling Approaches 4. The synthesis of Cephalosporins via Allenylazetidinones 5. Conclusion",10.1055/s-1994-22932,1994-01-01,0.6068541582473026
Organic Letters,Fast and Protecting-Group-Free Synthesis of (±)-Subincanadine C,"The first total synthesis of (±)-subincanadine C has been accomplished in a protecting-group-free fashion. This pentacyclic indole alkaloid was synthesized in six steps from the known intermediate 4, featuring Ni(COD)(2)-mediated intramolecular Michael addition as a key transformation.",10.1021/ol202349g,2011-10-04,0.6068520796721756
Journal of Organic Chemistry,Synthesis of Perfluoro[2.2]paracyclophane,"A synthesis of perfluoro[2.2]paracyclophane has been sought ever since the partially fluorinated octafluoro[2.2]paracyclophane (AF4) was prepared and its chemistry studied. This compound has now been prepared in 39% yield from the precursor, 1,4-bis(chlorodifluoromethyl)-2,3,5,6-tetrafluorobenzene by its reaction with Zn when heated in acetonitrile at 100 degrees C. Two preparations of the precursor, first from 1,4-dicyano-2,3,5,6-tetrachlorobenzene and an improved method beginning from 1,2,4,5-tetrachlorobenzene, are also described as are key comparisons to our related synthesis of AF4.",10.1021/jo7026849,2008-02-27,0.6068510584224944
European Journal of Organic Chemistry,Synthetic Studies Towards the Core Structure of Nakadomarin A by a Thioamide‐Based Strategy,"-acyliminium ion derived from a secondary thiolactam. In addition, a novel three-component coupling reaction between a thioamide, an allylic bromide and an isocyanate, leading to the establishment of two new stereogenic centres, is reported. Two key steps in a projected total synthesis of nakadomarin A have been realised by using the unique chemistry of thioamides. Formation of the carbocyclic B ring can be effected by nucleophilic attack of a furan on a thiolactam-derived iminium ion, and the key quaternary centre can be established by a novel three-component coupling reaction.",10.1002/ejoc.201301063,2013-11-14,0.6068486308815318
Organic Letters,Asymmetric Total Synthesis of (−)-Guignardones A and B,"The asymmetric total synthesis of (−)-guignardones A ( 2 ) and B ( 1 ) has been accomplished. The highly oxidized 6-oxabicyclo[3.2.1]octane core was constructed from d -quinic acid via substitution/desulfurization reaction with thiophenol to forge the bridged ring scaffold, and a Pummerer rearrangement and 1,4-addition/elimination sequence was employed to install the β-carbonyl group at the congested C-1 position. A late-stage Knoevenagel condensation–6π-electrocyclization and directed hydrogenation formed (−)-guignardone B ( 1 ), which was subjected to dehydration to furnish (−)-guignardone A ( 2 ).",10.1021/acs.orglett.0c00241,2020-02-10,0.6068356505927353
Chemical Science,"A sustainable, efficient, and potentially cost-effective approach to the antimalarial drug candidate MMV688533","A 6-step synthesis of the antimalarial drug candidate MMV688533 is reported. Key transformations carried out under aqueous micellar conditions include two Sonogashira couplings and amide bond formation. Compared with the first-generation manufacturing process reported by Sanofi, the current route features ppm levels of palladium loading, less material input, less organic solvent, and no traditional amide coupling reagents. The overall yield is improved ten-fold, from 6.4% to 67%.",10.1039/d3sc01699d,2023-01-01,0.6068355508154312
Tetrahedron,A novel route to organonitrites by Pd-catalyzed cross-coupling of sodium nitrite and potassium organotrifluoroborates,,10.1016/j.tetlet.2012.12.047,2012-12-22,0.6068345663686815
Tetrahedron,An enantioselective route to pyrrolidines: Removal of the chiral template from homochiral pyrroloimidazoles,,10.1016/0040-4039(96)00114-1,1996-03-01,0.6068235293569545
Tetrahedron,"Diastereoselective synthesis of 1-(tetrahydrofuran-3-yl)-1,3-dihydroisobenzofuran derivatives via Prins bicyclization",,10.1016/j.tetlet.2013.01.006,2013-01-11,0.6068211273061533
European Journal of Organic Chemistry,Efficient Synthesis of New Steroids Possessing an Aromatic A-Ring with a 2-Hydroxy or a 2-Fluoro Substituent,"5-Fluoro-1-iodobenzocyclobutene (7) and 5-tert-butoxy-1-iodobenzocyclobutene (8) have been used for the synthesis of the title compounds. This strategy involves the use of an intramolecular Diels−Alder cycloaddition of o-xylylenes as the key step. We have shown that the introduction of a tert-butyl ether as a protecting group at the beginning of the synthesis, in place of the methyl ether used previously, is a judicious choice by which to obtain steroids possessing an aromatic A-ring with a 2-OH substituent. Finally, the vinyl groups of the synthesized fluoro and hydroxy steroids have been oxidized by the Wacker process in good yields. An X-ray crystal structure of the fluoro steroid 14b, the trans-anti-trans ring configuration of which matches those in natural products, is reported.",10.1002/1099-0690(20021)2002:1<151::aid-ejoc151>3.0.co;2-f,2002-01-01,0.606816247477972
Synthesis,Deployment of Aziridines for the Synthesis of Alkaloids and Their Derivatives,"Various (activated and non-activated) aziridines with diverse substitution patterns have been deployed successfully as starting materials for the synthesis of a wide variety of alkaloids via suitable functionalization and aziridine ring transformation. Alternatively, the preparation and interception of reactive aziridine intermediates has also been shown to constitute a valid approach toward alkaloid synthesis. This review summarizes aziridine-mediated syntheses of alkaloids, in which the aziridine is mobilized as either a substrate or an advanced synthetic intermediate. 1 Introduction 2 Alkaloids Synthesis from Aziridine Starting Materials 2.1 (2R)- and (2S)-Hydroxymethyl-N-(1-phenylethyl)aziridines 2.2 N-Benzylaziridine-2-carboxylates 2.3 2-Substituted N-Tosyl- or N-Tritylaziridines 2.4 2,3-Disubstituted N-Cbz- or N-Tosylaziridines 2.5 N-DMB-aziridines 3 Alkaloids Synthesis from Aziridines as Key Advanced Synthetic Intermediates 3.1 Alkylative Aziridine Ring Opening 3.2 Arylative Aziridine Ring Opening 3.3 Ring Expansion 3.4 Oxidative Aziridine Ring Opening 3.5 Heteroatomic Nucleophilic Aziridine Ring Opening 3.6 Reductive Aziridine Ring Opening 4 Conclusion",10.1055/s-0037-1611715,2019-02-18,0.6068088463043597
Tetrahedron,"The regioselective synthesis of enantiomerically pure myo-inositol derivatives. Efficient synthesis of myo-inositol 1,4,5-trisphosphate.",,10.1016/s0040-4039(00)74142-6,1992-01-01,0.6068084418369586
Synlett,Enantioselective Synthesis of 6-nor-Fluvirucinin B<sub>1</sub>,"An enantioselective synthesis of the 6-nor-derivative 3 of the antiviral macrocyclic lactam fluvirucinin B1 (2) is presented. Key steps are two regioselective ring opening reactions of chiral epoxides, and a ring-closing metathesis with Grubbs’ catalyst. The choice of appropriate protective groups was essential for the success and efficiency of the synthesis.",10.1055/s-2002-34214,2002-01-01,0.6068021634146408
Organic Letters,Total Synthesis and Stereochemical Assignment of (−)-Psychotridine,"We report the first enantioselective total synthesis and stereochemical assignment of (-)-psychotridine. The application of our diazene-directed assembly of enantiomerically enriched cyclotryptamines afforded a highly convergent synthesis of the pentameric alkaloid, allowing its detailed structural assignment. Highlights of the synthesis include the introduction of four quaternary stereocenters with complete stereochemical control in a single step via the photoextrusion of three molecules of dinitrogen from an advanced intermediate and metal-catalyzed C-H amination reactions in challenging settings.",10.1021/acs.orglett.2c00448,2022-03-17,0.6067896072674377
European Journal of Organic Chemistry,"Synthesis of Enantiomerically Pure 2′,3′,5′-Trideoxy-4′-[(diethoxyphosphoryl)difluoromethyl]thymidine Analogues","D- and L-(diethoxyphosphoryl)difluoromethyl nucleoside analogues 10 have been synthesized using the building block approach, starting from chiral fluorinated molecules. The key steps of the synthetic sequence were condensation of 2-methyl-5-(4-methylphenylsulfinyl)pent-2-ene (1) and ethyl 2-(diethoxyphosphoryl)-2,2-difluoroacetate (2), reduction of the thus formed ketones 3 to alcohols 4, reductive removal of the sulfur moiety to give hydroxy phosphonates 6, and oxidative cyclization to give furanose derivatives 8.",10.1002/(sici)1099-0690(199909)1999:9<2149::aid-ejoc2149>3.0.co;2-d,1999-09-01,0.6067746440128197
European Journal of Organic Chemistry,"Synthesis of Enantiomerically Pure 2′,3′,5′-Trideoxy-4′-[(diethoxyphosphoryl)difluoromethyl]thymidine Analogues","D- and L-(diethoxyphosphoryl)difluoromethyl nucleoside analogues 10 have been synthesized using the building block approach, starting from chiral fluorinated molecules. The key steps of the synthetic sequence were condensation of 2-methyl-5-(4-methylphenylsulfinyl)pent-2-ene (1) and ethyl 2-(diethoxyphosphoryl)-2,2-difluoroacetate (2), reduction of the thus formed ketones 3 to alcohols 4, reductive removal of the sulfur moiety to give hydroxy phosphonates 6, and oxidative cyclization to give furanose derivatives 8.",10.1002/(sici)1099-0690(199909)1999:9<2149::aid-ejoc2149>3.3.co;2-4,1999-09-01,0.6067746440128197
Synlett,"Towards a Total, Genetically Engineered Synthesis of Vitamin B<sub>12</sub>","All articles of this category The complete biosynthetic pathway to vitamin B 12 has recently been elucidated in the aerobic organism Pseudomonas denitrificans . By cloning and overexpressing the biosynthetic genes necessary for corrin synthesis it has been possible not only to study the steps catalyzed by each enzyme in turn, but by recombining all twelve enzymes in a single flask with the necessary cofactors, the total synthesis of hydrogenobyrinic acid, an advanced corrinoid precursor of the vitamin has been accomplished in 20% overall yield, from 5-aminolevulinic acid. 1. Introduction 2. The ""Early"" Stages: From ALA to Precorrin-3 3. The Steps beyond Precorrin-3 in the Aerobic P. denitrificans 4. Multi-enzyme Synthesis of Corrins",10.1055/s-1994-23038,1994-01-01,0.6067738193999933
Organic Letters,New Total Synthesis of the Marine Antitumor Alkaloid (−)-Agelastatin A,"[reaction: see text] A new total synthesis of (-)-agelastatin A (1) has been achieved from the chiral oxazolidinone (-)-3. Although enone transposition was problematic when the Michael ring closure of 2 was attempted with strong base, the desired cyclization could be effected with Hunig's base after the pyrrole nucleus was brominated. Subsequent reduction and monobromination afforded synthetic (-)-agelastatin A (1).",10.1021/ol0490476,2004-06-19,0.6067659596189122
Tetrahedron,"2-dipropylborylmethyl-1,3-butadiene - a new reagent for isoprenylation. Efficient synthesis of ipsenol and ipsdienol",,10.1016/s0040-4039(00)94915-3,1985-01-01,0.6067475683167183
Organic Process Research & Development,Preparation of the HIV Attachment Inhibitor BMS-663068. Part 7. Development of a Regioselective Ullmann–Goldberg–Buchwald Reaction,"The discovery, development, and optimization of an Ullmann–Goldberg–Buchwald coupling reaction is described. This complex process represents a key transformation in the development of a commercially viable synthesis of the HIV attachment inhibitor prodrug BMS-663068. In this reaction, high regioselectivities were obtained for the coupling of a 1,2,4-triazole and a 7-bromoazaindole, preparing BMS-626529, the antepenultimate in good yield and quality. Key challenges associated with developing commercially viable conditions for this copper-mediated coupling include achieving the desired level of regiochemical control, identifying robust isolation conditions and controlling residual copper levels in the isolated product.",10.1021/acs.oprd.7b00191,2017-08-09,0.6067475504411332
Green Chemistry,Electrochemically catalyzed amino-oxygenation of styrenes: n-Bu <sub>4</sub> NI induced C–N followed by a C–O bond formation cascade for the synthesis of indolines,An efficient indirect electrochemical amino-oxygenation of styrenes has been developed for the synthesis of 3-alkoxyindolines.,10.1039/c5gc02626a,2015-11-26,0.6067475340569697
Synthesis,Synthesis of Cyclitols via Cyclopropanation/Palladium-Catalyzed Ring Opening,"The stereoselective syntheses of three cyclitols, 5a-carba-α-d-rhamnopyranose, 5a-carba-β-d-digitoxopyranose, and 5a-carba-α-l-rhamnopyranose, have been achieved. The routes rely upon a Simmons-Smith cyclopropanation and diastereospecific ring opening of cyclopropanol under Pd/C hydrogenation conditions to prepare the α-methyl ketone. A sequence of diastereoselective reduction, dihydroxylation, and/or Myers' reductive 1,3-rearrangement were used to install the desired stereochemistry.",10.1055/s-2008-1067262,2008-09-05,0.6067333764265216
Organic Letters,A Tether Controlled <i>e</i><i>xo</i>-Selective Trans-Annular Diels−Alder (TADA) Reaction,"[reaction: see text] A fully substrate controlled stereoselective route to construct cis-hexahydronaphthalene 4 is described starting from nonracemic butenolide 6. The key step is an exo-selective transannular Diels-Alder reaction (TADA) of tetraene 5, whose intrinsic constraint allows selective formation of one stereodefined product. Compound 4 is a key intermediate in the synthesis of the novel antibiotic branimycin (1).",10.1021/ol061510m,2006-07-21,0.6067323446497553
Journal of the American Chemical Society,The Catalytic Asymmetric Total Synthesis of Elatol,"Described in this report is the first total synthesis of elatol, a halogenated sesquiterpene in the chamigrene natural product family. The key disconnections in our synthetic approach include an enantioselective decarboxylative allylation to form the all-carbon quaternary stereocenter and a ring-closing olefin metathesis to concomitantly form the spirocyclic core as well as the fully substituted chlorinated olefin. This strategy represents a general platform for accessing the chamigrene natural product family, as demonstrated by the synthesis of (+)-laurencenone B as an intermediate in our route.",10.1021/ja710294k,2007-12-29,0.6067148251904178
Organic Letters,Formal Nucleophilic Substitution of Bromocyclopropanes with Amides en route to Conformationally Constrained β-Amino Acid Derivatives,A chemo- and diastereoselective protocol for the formal nucleophilic substitution of 2-bromocyclopropylcarboxamides with secondary amides is described. This method allows for convergent and highly selective synthesis of trans-β-aminocyclopropane carboxylic acid derivatives.,10.1021/ol101228k,2010-08-20,0.6067124547379327
Synlett,"Transition Metal Complexes in Organic Synthesis, Part 71:First Total Synthesis of Furoclausine-A","The first total synthesis of the furo[3,2-a]carbazole alkaloid furoclausine-A is described using an iron-mediated construction of the carbazole framework and an acid-catalyzed annulation of the furan ring as key steps.",10.1055/s-2004-815417,2004-01-01,0.6067101270458857
Synlett,Synthesis of the Tetrahydropyran Subunit (C8-C20 Fragment) of (-)-Dactylolide and (-)-Zampanolide,"The asymmetric synthesis of the tetrahydropyran containing C8-C20 fragment, a common key subunit of both (-)-dactyl­olide and (-)-zampanolide, is described. The salient feature of this synthesis is the extension of carbon chains using alkynols followed by the use of an alkyne system to generate the desired functionalities, in particular formation of the embedded pyran via an intramolecular oxa-Michael addition of a β-hydroxyynone.",10.1055/s-0029-1219931,2010-05-10,0.6067043975662111
Tetrahedron,"Total synthesis of U- 71,184, s potent new antitumor agent modeled on cc-1065",,10.1016/s0040-4039(00)84921-7,1986-01-01,0.6066920439205753
Tetrahedron,Intramolecular cyclization of tris-∝-diazoketones: a new stepwise synthesis of bullvalene,,10.1016/s0040-4039(01)84881-4,1972-01-01,0.6066896780715606
Tetrahedron,Intramolecular cyclization of diazoketones: new stepwise synthesis of semibullvalene,,10.1016/s0040-4039(01)83564-4,1977-01-01,0.6066896780715606
Journal of Organic Chemistry,"New Synthetic Strategies to Vitamin D Analogues Modified at the Side Chain and D Ring. Synthesis of 1α,25-Dihydroxy-16-ene-vitamin D<sub>3</sub>and C-20 Analogues<sup>1</sup>","Two efficient synthetic routes to 1alpha,25-dihydroxy-16-ene-vitamin D(3) (4a) and their C-20 analogues (3 and 4) have been developed. Key features common to both routes A and B are the introduction of side chains functionalized at C20 (17, 21, 19, and 25). In route A the CD side chain fragments 5 and 6 are prepared by S(N)2' syn displacement of allylic carbamates 8 and 9 (X = OCONHPh) by Li(2)Cu(3)R(5). The triene unit is then constructed by assembling the latter fragments with the A-ring fragment using the Wittig-Horner method (average yield of vitamin D analogue 35%, 11-13 steps from ketone 11). In route B, the S(N)2' syn displacement of the carbamate moiety by Li(2)Cu(3)R(5) is carried out on intermediates 12 and 13, both of which bear the vitamin D triene unit (average yield of vitamin D analogue 27%, 13-15 steps from ketone 11). The latter route is particularly attractive as an approach to diverse C-20 vitamin D analogues for biological screening.",10.1021/jo982393e,1999-04-01,0.6066862640682539
Journal of Organic Chemistry,Analogues of Key Precursors of Aspartyl Protease Inhibitors:  Synthesis of Trifluoromethyl Amino Epoxides,"The synthesis of the title compound is described through original and tailored synthetic protocols. The addition of vinylmagnesium bromide to CF(3)-N-aryl and N-alkyl aldimines was efficient and did not require an activating N-substituent. The resultant CF3-allylamines were converted in an efficient and completely stereoselective route to syn CF3-epoxides 3 via formation of bromhydrins 8. The same sequence performed from the aldimine substituted with the methyl ether of the (R)-phenylglycinol provided the homochiral (R,R)-amino epoxide (de >98%). This study has allowed access to the novel racemic and homochiral trifluoromethyl beta-amino epoxides, analogues of key precursors of various HIV protease inhibitors.",10.1021/jo0485233,2004-12-10,0.6066661178999105
Organic Letters,New Strategy for the Total Synthesis of Macrosphelides A and B Based on Ring-Closing Metathesis,"[reaction: see text] A new total synthesis of macrosphelides A and B using ring-closing metathesis (RCM) as a macrocyclization step is described. The substrate of the RCM could be synthesized from readily available chiral materials, methyl (S)-(+)-3-hydroxybutyrate and methyl (S)-(-)-lactate, with a high efficiency. The RCM proceeded in the presence of Grubbs' Ru-complex, providing a new effective synthetic route to these natural products.",10.1021/ol0350689,2003-07-17,0.6066609938460589
Synlett,Gold(I)-Catalyzed Domino Cyclization for the Synthesis of Tricyclic Chromones,"A simple and efficient method for the synthesis of tricyclic chromones has been developed. In this approach, tricyclic chromones were synthesized from a diverse range of phenols and alkynes through a Sonogashira coupling and subsequent gold-catalyzed intramolecular domino cyclization.",10.1055/s-0034-1380715,2015-06-03,0.6066581114323965
Journal of Organic Chemistry,"Suzuki−Miyaura Approach to JNJ-26076713, an Orally Active Tetrahydroquinoline-Containing α<sub>V</sub>β<sub>3</sub>/α<sub>V</sub>β<sub>5</sub> Integrin Antagonist. Enantioselective Synthesis and Stereochemical Studies","An improved scale-up synthesis was required for the alpha(V)beta(3)/alpha(V)beta(5) integrin antagonist 1, which had demonstrated oral efficacy in eye disease models of angiogenesis and vascular permeability. A stereodefined, quinoline-substituted, unsaturated ester was conveniently prepared by a Suzuki-Miyaura coupling to facilitate exploration of multiple methods of asymmetric reduction. The catalytic chiral hydrogenation of the corresponding unsaturated acid (Z-5b) with a ruthenium-based metal precursor and the (R)-XylPhanePhos ligand proved particularly efficient and economical. The resulting (3S)-quinoline-containing intermediate was reduced to an equal mixture of tetrahydroquinoline diastereomers. The undesired diastereomer could be recycled to the desired one by an oxidation/reduction protocol. The absolute stereochemistry of 1 was established as 3S,3'S by a combination of X-ray diffraction and chemical means.",10.1021/jo702551t,2008-02-16,0.6066575253238972
Journal of Organic Chemistry,"Formal Total Synthesis of Manzacidin C Based on Asymmetric 1,3-Dipolar Cycloaddition of Azomethine Imines","An enantioselective formal total synthesis of (+)-manzacidin C is described. A key feature of the synthesis is the construction of two chiral centers via the asymmetric 1,3-dipolar cycloaddition of an azomethine imine to methallyl alcohol by the use of (S,S)-DIPT as a chiral auxiliary.",10.1021/acs.joc.6b02816,2017-01-16,0.6066547717111309
Journal of Organic Chemistry,"Synthesis of Microcolin B, a Potent New Immunosuppressant Using an Efficient Mixed Imide Formation Reaction","Microcolin B, a potent new immunosuppressant isolated from blue-green alga Lyngbya majuscula off the Venezuelan coast, has been made using a methyl-directed asymmetric hydrogenation reaction with rhodium on alumina catalyst on lactone 4 for the synthesis of the key ( R,R )-2,4-dimethyloctanoic acid fragment 1 . A new, direct mixed imide formation reaction was also developed for the production of the unusual prolylpyrrolen-2-one 2 portion of microcolin. The pentafluorophenyl ester of CBZ-proline 5 was reacted with the lithium imidate of lactam 6, providing the mixed imide in 80% yield. Coupling of acid 1 with the N-terminus of the tripeptide, followed by coupling with pyrrolylproline 2, gave microcolin B. The new mixed-imide forming reaction was also applied to a formal total synthesis of microcolin A. The pentafluorophenyl ester of TBS-protected cis -hydroxyproline was coupled with lactam 6, and the resultant imide was converted to the key pyrrolylproline made previously for microcolin A.",10.1021/jo970387x,1997-08-01,0.6066528844145912
Angewandte Chemie International Edition,Bioinspired Synthesis of Cucurbalsaminones B and C,"Cucurbalsaminones B (1) and C (2) are two abeo-cucurbitane triterpenoids with a unique 5/6/3/6/5-fused ring system and exhibit potent multidrug resistance (MDR)-reversing activity. Herein, we report the first synthesis of these two natural products, both of them were accomplished in 14 steps from commercially available inexpensive resource compound lanosterol. Key features of this synthesis include a biomimetic tandem Wagner-Meerwein type lanostane-to-cucurbitane rearrangement followed by a bioinspired photochemical oxa-di-π-methane (ODPM) rearrangement to complete the skeleton construction and an Eosin Y photoinduced Barton-McCombie deoxygenation to realize the challenging oxidation state adjustment of the sterically hindered C11 position.",10.1002/anie.202417318,2024-11-06,0.6066498195643569
Organic Letters,Structure Revision and Syntheses of Epohelmins A and B,"[structures: see text] Epohelmins A (24) and B (26) have been reassigned as pyrrolizidin-1-ols, rather than the proposed 9-oxa-4-azabicyclo[6.1.0]nonane structures 1 and 2, respectively. Syntheses of epohelmin A (24) (eight steps, 52% overall yield) and epohelmin B (26) (11 steps, 43% overall yield) have been achieved starting from N-Cbz-(S)-prolinal (9) and ortho ester ketone 17 using a stereoselective aldol reaction and a stereoselective reductive cyclization as the key steps.",10.1021/ol0516061,2005-09-01,0.606648686719971
Tetrahedron,Facile synthesis of polyhydroxycoumaronochromones with quinones: synthesis of alkylpolyhydroxy- and alkoxycoumaronochromones from 2′-hydroxyisoflavones,,10.1016/s0040-4039(01)01234-5,2001-08-01,0.6066472680024302
Synthesis,"An Efficient Synthesis of (2<b><i>S,</i></b>6S)- and meso-Diaminopimelic Acids via Asymmetric Hydrogenation","An efficient synthesis of the title compounds 1 and 2 has been successfully developed. The key step is the asymmetric hydrogenation of dehydroamino acid 7 using [Rh(I)(COD)-(S,S) or -(R,R)-Et-DuPHOS)]+OTf- to produce the optically active, protected amino acid derivatives in high ee (>95%). The approach also can be used for the synthesis of other isomers and analogues.",10.1055/s-2002-19295,2002-07-26,0.6066454906520521
Tetrahedron,An efficient synthesis of a novel analog of octreotide with an unnatural l-lysine-like tetrazolyl amino acid,,10.1016/j.tetlet.2014.07.067,2014-07-24,0.6066296887387824
European Journal of Organic Chemistry,"Regioselective Synthesis of Benzo[<i>h</i>][1,6]‐naphthyridines and Chromenopyrazinones through Alkyne Cyclization","A regioselective approach to the synthesis of benzo[ h ][1,6]‐naphthyridine and chromenopyrazinone derivatives was developed. The synthetic route to benzo[ h ][1,6]‐naphthyridines involves the N ‐propargylation of aromatic aminobenzaldehydes, followed by reaction with propargylamine in the presence of DBU (1,8‐diazabicyclo[5.4.0]undec‐7‐ene). For the synthesis of chromenopyrazine and chromenopyrazinone derivatives, the acetonitrile group was introduced to salicylaldehyde derivatives, and a DBU‐promoted cyclization reaction between aldehydes and propargylamine gave the chromenopyrazines. The intramolecular heterocycloaddition reaction between the triple bond and the azadiene, which is formed as an intermediate, gave the desired structures.",10.1002/ejoc.201601661,2017-01-25,0.6066205938148181
Journal of Organic Chemistry,A Facile One-Pot Preparation of Alkyl Aminoaryl Sulfides for the Synthesis of GW7647 as an Agonist of Peroxisome Proliferator-Activated Receptor α,"We have developed two simple and high yielding one-pot syntheses of alkyl aminoaryl sulfides containing a series of four-steps: in situ protection of the free amine by reaction with a Grignard reagent, halogen-lithium exchange, sulfur insertion, and a substitution reaction with various electrophiles. Through this protocol, we have successfully synthesized tert-butyl-2-[4-(2-aminoethyl)phenylsulfanyl]-2-methylpropanoate, a key intermediate for the synthesis of GW7647 and GW9578 (ureido-TiBAs), in 92% yield. Furthermore, we were able to improve the overall yield of GW7647 to 66%, 3 times the yield previously reported.",10.1021/jo060361i,2006-06-28,0.6066048121295914
Synlett,Synthesis of (+)-Azafagomine from D-xylose,All articles of this category L-glucose resembling enantiomer of the racemic glycosidase inhibitor azafagomine was synthesised from D-xylose and found to be inactive. azasugar - glycosidase inhibitor - hydrazine - reductive amination,10.1055/s-1999-2716,1999-06-01,0.60660421387556
Journal of Organic Chemistry,Electrochemical Synthesis and Chemistry of Chiral 1-Cyanotetrahydroisoquinolines. An Approach to the Asymmetric Syntheses of the Alkaloid (−)-Crispine A and Its Natural (+)-Antipode,"The stereoselective convergent total syntheses of both enantiomers of the tetrahydroisoquinoline (THIQ) alkaloid crispine A are described. The THIQ precursors (-)-6 (90:10 dr) and (-)-11 (85:15 dr) were prepared from the alkylation-reduction sequence of a common α-amino nitrile (+)-4 derivative that has been conveniently prepared by anodic cyanation. Elaboration of the pyrrolidine ring of the title compound was cleanly achieved by two efficient ring closures methods involving (a) the displacement of a halogen atom and (b) the formation of a cyclic iminium cation to afford (-)-crispine A in 90% and 85% yields, respectively. A crystallization of enantioenriched (-)-crispine A (90:10 er) with 1 equiv of (-)-DBTA afforded the tartrate salt (-)-14 (≥98:2 dr) in 81% yield. The absolute S configuration of (-)-crispine A was simply deduced from examination of the X-ray data of tartrate salt (-)-14. Likewise, the natural (+)-crispine A was prepared in seven workup steps in an overall 30% yield, and reciprocal crystallization with (+)-DBTA afforded the enantiomeric tartrate salt (+)-14 in a ≥98:2 dr. Both enantiomers of crispine A were liberated from their respective DBTA salts in ≥98:2 er's which were determined by proton and carbon NMR spectroscopy, utilizing (R)-(+)-tert-butylphenylphosphinothioic acid (+)-15 as chiral solvating agent.",10.1021/jo2017982,2011-10-21,0.6066013762906312
Angewandte Chemie International Edition,Nickel‐Catalyzed Cross‐Electrophile Coupling to Access Polysubstituted Cyclobutenes,"Abstract The synthesis of cyclobutenes remains inefficient owing to inherent ring strain and poor regioselectivity. We describe herein a nickel‐catalyzed cross‐electrophile coupling (XEC) between readily accessible homopropargyl halides and commercially available aryl/vinyl electrophiles for direct access to polysubstituted cyclobutenes. This approach provides the first reductive 4 ‐endo‐dig cyclization with high chemo‐ and regioselectivity, which paves the way for the synthesis of diverse cyclobutene containing compounds (including synthetically challenging macrocycles). The synthesis of an antitumor‐active combretastatin A‐4 analog has been significantly optimized; the original six‐step procedure yielding 14% has been streamlined into a three‐step process with a markedly improved yield of 51%. Experimental data and computational studies support a mechanism involving an alkenyl nickel(I) intermediate, which undergoes facile back‐side S H 2 attack to produce the strained cyclobutene ring with overall stereoinversion at the homopropargylic position.",10.1002/anie.202507087,2025-05-13,0.6065928186784318
Synlett,A Novel Synthesis of Methyl [6-(α-methoxyimino)ethyl]salicylate,All articles of this category A highly efficient synthesis of the title compound was accomplished by employing the directed ortho lithiation in toluene at room temperature and methoxyiminodeacetallization as key steps from 3-hydroxyacetophenone.,10.1055/s-1994-22738,1994-01-01,0.6065910221139919
Journal of Organic Chemistry,"Bu<sub>3</sub>SnH-Mediated Pinacol Coupling of 1,5- and 1,6-Dicarbonyl Compounds:  Synthetic and Mechanistic Studies","A new method is described for the intramolecular pinacol coupling of 1,5- and 1,6-dicarbonyl compounds, employing Bu(3)SnH as the stoichiometric reductant. The key steps in this pinacol cyclization are the addition of a tin ketyl to a carbonyl group and a subsequent intramolecular S(H)2 reaction. The isolation of 1,3-dioxa-2-stannolanes, along with other product and labeling studies, provides strong support for the proposed homolytic substitution step, which distinguishes the pinacol cyclization from other reductive cyclizations of tin ketyls, all of which proceed through abstraction of hydrogen from Bu(3)SnH in the final step. An interesting consequence of the S(H)2 pathway is very high cis selectivity in the cyclization of 1,5-dicarbonyl compounds. Mechanistic studies furnish evidence that the steps that precede homolytic substitution, including C-C bond formation, are reversible under the reaction conditions.",10.1021/jo9809130,1998-08-12,0.6065817901323095
Journal of Organic Chemistry,One-Pot Tandem Aldol-Cycloetherification Protocol in the Enantioselective Synthesis of Davanoids,"Total synthesis of cis and trans diastereomers of prenylated davanoids like davanone, nordavanone, and davana acid ethyl ester was achieved in an enantioselective strategy. Various other davanoids could also be synthesized using standard procedures from the Weinreb amides derived from davana acids. Enantioselectivity in our synthesis was achieved employing a Crimmins’ non-Evans syn aldol reaction that fixed the stereochemistry of the C3-hydroxyl group, while the C2-methyl group was epimerized in a late stage of the synthesis. A Lewis acid-mediated cycloetherification reaction was used to establish the tetrahydrofuran core of these molecules. Interestingly, a slight alteration of the Crimmins’ non-Evans syn aldol protocol led to the complete conversion of the aldol adduct to the core tetrahydrofuran ring of davanoids, thus essentially dovetailing two important steps in the synthesis. The resulting one-pot tandem aldol-cycloetherification strategy enabled the enantioselective synthesis of trans davana acid ethyl esters and 2- epi -davanone/nordavanone in just three steps in excellent overall yields. The modularity of the approach will enable the synthesis of various other isomers in stereochemically pure forms for further biological profiling of this important class of molecules.",10.1021/acs.joc.2c02865,2023-02-22,0.6065815736408793
Tetrahedron,Reaction of acyl carbonylferrate(o) with nitro compound. A new synthetic route to amide,,10.1016/s0040-4039(01)91622-3,1976-05-01,0.6065788858002715
Angewandte Chemie International Edition,Stereocontrolled Total Synthesis of (+)‐UCS1025A,"Under control: A stereocontrolled total synthesis of (+)-UCS1025A, a potent telomerase inhibitor, was achieved. The synthesis features an intramolecular Diels–Alder reaction, a tandem Staudinger/aza-Wittig reaction, and stereoselective construction of the hemiaminal moiety facilitated by neighboring-group participation.",10.1002/anie.201207800,2012-11-09,0.6065708285450391
Organic Letters,"Intramolecular Fischer Indole Synthesis for the Direct Synthesis of 3,4-Fused Tricyclic Indole and Application to the Total Synthesis of (−)-Aurantioclavine","Aryl hydrazides with a ketone or aldehyde containing side chains linked to the meta-position of the aromatic ring undergo acid-promoted intramolecular Fischer indole synthesis to generate 3,4-fused tricyclic indoles. The preparative utility of this conceptually new synthetic approach, which does not require prefunctionalization of the indole ring, was demonstrated by its application to a concise total synthesis of (-)-aurantioclavine.",10.1021/acs.orglett.6b02541,2016-09-19,0.6065664902607404
Organic Letters,General Synthesis of the Nitropyrrolin Family of Natural Products via Regioselective CO<sub>2</sub>-Mediated Alkyne Hydration,"The total synthesis of the 2-nitropyrrole natural products nitropyrrolins A and B and the formal synthesis of nitropyrrolin D are reported. The key 2-nitro-4-alkylpyrrole core was efficiently assembled by Sonogashira cross-coupling, with complete control of regioselectivity. An unusual carboxylative cyclization, sulfonylcarbamate formation, and base-promoted cleavage sequence enabled access to the key hydroxy ketone without affecting the protected 2-nitropyrrole unit. The total synthesis provides a general approach for preparation of the bioactive nitropyrrolin family of natural products.",10.1021/acs.orglett.7b02687,2017-09-12,0.6065629262988284
Organic Letters,A Convergent Stereoselective Total Synthesis of Racemic Phthoxazolin A,"The first total synthesis of phthoxazolin A is reported which involves a convergent series of palladium-catalyzed cross-coupling reactions to stereoselectively construct the Z, Z, E -trienyl unit of phthoxazolin A. The most important steps of the synthesis involve using vinylboronate pinacol ester as a vinyl dianion equivalent, by employing a Heck coupling of a vinyl iodide with the vinylboronate, followed by a deboronation−iodination sequence with inversion of alkene stereochemistry and Stille coupling of the resulting vinyl iodide.",10.1021/ol990967b,1999-09-14,0.6065533576990363
Tetrahedron,Total synthesis of (−)-detoxin D1,"An efficient stereocontrolled total synthesis of (−)-detoxin D1, the most active component of the detoxin complex, is described.",10.1016/s0040-4039(00)92511-5,1992-06-01,0.6065510296215963
Synthesis,"A Simple and Efficient Total Synthesis of a Styryllactone, 7-<i>epi</i>-Goniodiol","Regioselective mono-dihydroxylation, Red-Al reduction, and cis-Horner-Wadsworth-Emmons reactions have been efficiently performed as key steps in the synthesis of 7-epi-goniodiol, isolated from Goniothalamus leiocarpus.",10.1055/s-2007-965879,2007-01-25,0.6065454766855328
Synthesis,Structure Investigations of (ent)-Cladospolide D by De Novo Synthesis and Kinetic and Thermodynamic Isomerization,The de novo asymmetric synthesis of cladospolides B and C and (ent)-cladospolide D has been achieved from achiral non-1-yne. The 11-13-step route relies upon a Noyori reduction and a KAPA promoted alkyne zipper reaction to relay an achiral functionality across a nine-carbon fragment and to enable the installation of a dienoate functionality. A diastereo- and regioselective Sharpless dihydroxylation of a dienoate installed the remaining stereochemistry. The de novo asymmetric route allowed for the asymmetric synthesis of three members of the cladospolide natural products and correctly established the structure for cladospolide D.,10.1055/s-0029-1217606,2009-07-10,0.6065371160154877
Organic Letters,First Total Synthesis of Xestobergsterol A and Active Structural Analogues of the Xestobergsterols<sup>1</sup>,"[formula: see text] A novel pentacyclic polyhydroxylated sterol, xestobergsterol A (1a), has been synthesized in 24 steps and in good overall yield from stigmasterol 17. The key steps of the synthesis are the Breslow remote functionalization of the polyoxygenated steroid derived from 25 and the base-catalyzed epimerization-aldol condensation of the dione derived from 27.",10.1021/ol991057x,1999-10-10,0.6065310575014187
Organic Letters,"Tandem Reaction of Propargylic Alcohol, Sulfonamide, and <i>N</i>-Iodosuccinimide: Synthesis of <i>N</i>-(2-Iodoinden-1-yl)arenesulfonamide",An efficient and straightforward strategy for the synthesis of N-(2-haloinden-1-yl)arenesulfonamides from propargylic alcohols and sulfonamides is described. Allenesulfonamide is postulated to be the key intermediate for this tandem transformation.,10.1021/ol103074d,2011-01-26,0.6065263192326251
Tetrahedron,"A new stereoselective route to (2S, 3S, 8S, 9S, 4E, 6E)-3-amino-9-methoxy-2, 6, 8-trimethyl-10-phenyldeca-4, 6-dienoic acid (Adda)",,10.1016/0040-4039(96)00282-1,1996-04-01,0.6065238747355437
Journal of Organic Chemistry,Asymmetric Synthesis of Cyclohexene Nucleoside Analogues,"The asymmetric synthesis of novel cyclohexene nucleoside analogues 12 and 15 is described. An enantiospecific Diels-Alder reaction between (E,E)-diene 2 and (+)-5-(d-mentyloxy)-2(5H)-furanone 3 provided the cycloadduct isomer 4. Three additional steps yielded amine 8 allowing the constructions of the thymine and adenine moieties to afford intermediates 11 and 14, respectively. Amination or cyclization and removal of the protecting groups occurred in one step in the presence of ammonia, giving the target six-membered ring nucleosides.",10.1021/jo2012708,2011-08-24,0.6065237809963288
Organic Process Research & Development,"Synthesis of Rovafovir Etalafenamide (Part I): Active Pharmaceutical Ingredient Process Development, Scale-Up, and Impurity Control Strategy","This manuscript describes the chemical process development and multi-kilogram synthesis of rovafovir etalafenamide (GS-9131), a phosphonamidate prodrug nucleotide reverse transcriptase inhibitor under investigation for the treatment of HIV-1 infection. Rovafovir etalafenamide is assembled in a four-step sequence beginning from the nucleoside core and an elaborated phosphonamidate alcohol. The assembly starts with a decarboxylative elimination of a β-hydroxyacid to yield the corresponding cyclic enol ether, which is subsequently coupled to a functionalized phosphonamidate alcohol in an iodoetherification reaction. Oxidative syn elimination then installs the required fluoroalkene, after which a final deprotection reaction yields the active pharmaceutical ingredient (API). Understanding the genesis, fate, and purge of the des -fluoro analog of the API, a mitochondrial toxin, proved to be a central driver in the development of the manufacturing route and impurity control strategy. Initial control strategies revolved around the use of silica gel chromatography or simulated moving bed chromatography to purge the des -fluoro impurity to an acceptable level, but ultimately a chromatography-free approach to mitigate the formation of this impurity was devised that expanded manufacturing flexibility. Design of experiments was used to improve the iodoetherification fragment coupling reaction and to reduce the level of the des -fluoro impurity formed in this step. Furthermore, several new crystalline intermediate forms were discovered and implemented as isolation points to bolster the overall impurity control strategy for standard, diastereomeric, and potentially mutagenic impurities as well as for the des -fluoro impurity. These processes were executed on multi-kilogram scale to produce API for clinical studies.",10.1021/acs.oprd.1c00059,2021-05-09,0.6065165517642551
European Journal of Organic Chemistry,Expedient Synthesis of Large‐Ring <i>trans</i>‐Enamide Macrolides by CuI‐Mediated Intramolecular Coupling of Vinyl Iodide with Amide: Total Synthesis of Palmyrolide A,"Abstract An efficient and improved procedure for copper‐catalyzed coupling of vinyl iodide with amide in an intramolecular fashion is described. The protocol utilizes a combination of copper iodide, CsF and (±)‐1,2‐diaminocyclohexane as ligand. The vinyl iodide couples efficiently with the amide to generate an enamide macrolide without any alteration in the double ‐bond geometry. The developed method was applied in the synthesis of several large‐ring enamide macrolides, and for the total synthesis of natural product palmyrolide A and homologated sanctolide A.",10.1002/ejoc.201600325,2016-04-24,0.6065160714906279
Tetrahedron,Taxol synthesis: Synthesis of A-ring and a methodology for substituted cyclohexadienes,,10.1016/s0040-4039(97)10038-7,1997-11-01,0.6065045508508448
Journal of the American Chemical Society,First Enantiospecific Total Synthesis of the Antitubercular Marine Natural Product Pseudopteroxazole. Revision of Assigned Stereochemistry,"A concise, enantiospecific synthesis of pseudopteroxazole (3), which had originally been assigned structure 1, has been accomplished starting from S-(-)-limonene. The known cyclohexanone 5 was converted in five steps to the alpha,beta-enone 8 by a modified Robinson annulation. Transformation of 8 to the orthogonally protected amino phenol 11 was accomplished by a new modification of the Wolff-Semmler rearrangement. The synthesis was completed by cationic cyclization to form 14 diastereoselectively and subsequent introduction of the terminal oxazole subunit.",10.1021/ja0378916,2003-10-10,0.6065042611488131
Organic Letters,Synthesis of Chiral Azabicycles from Pyroglutaminols,"The stereocontrolled synthesis of a range of substituted bicyclic morpholine and piperazine derivatives is reported from substituted pyroglutaminols via an intramolecular S N 2 cyclization as the key step. This enantiospecific approach toward chiral bicyclic morpholines and piperazines offers new opportunities to access these challenging ring systems, which are becoming increasingly common motifs in drug discovery.",10.1021/acs.orglett.6b03024,2016-10-27,0.6064997317735163
Journal of Organic Chemistry,Optical Resolution of 3-(Silyloxy)glutaric Acid Half Esters and Their Utilization for Enantioconvergent Synthesis of a HMG-CoA Reductase Inhibitor,"Useful chiral synthons, (3 R )- and (3 S )-[( tert -butyldimethylsilyl)oxy]pentanedioic acid monomethyl ester, ( R )- 1 and ( S )- 1, were obtained by optical resolution of a racemic mixture of 1 . Sulfoxide 8 has been developed from ( S )- 1 as a new building block for preparing HMG-CoA reductase inhibitors. Two alternate chiral synthons 2 and 8, synthesized from ( R )- 1 and ( S )- 1, respectively, were employed for enantioconvergent synthesis of potent inhibitor 15 containing a pyrrole moiety.",10.1021/jo9722156,1998-04-14,0.6064967502561992
Journal of the American Chemical Society,Total Synthesis of the Cyanolide A Aglycon,The synthesis of the potent molluscicide cyanolide A has been achieved in 10 steps without the use of protecting groups. The synthesis features a key Sakurai macrocyclization/dimerization reaction that simultaneously forms both tetrahydropyran rings and the macrocycle of the natural product.,10.1021/ja204228q,2011-06-03,0.6064948733782678
Organic Letters,Total Synthesis of Gambierol,"The total synthesis of gambierol has been achieved utilizing an oxiranyl anion strategy in an iterative manner. Synthetic highlights of this route include direct carbon-carbon formation on epoxides, sulfonyl-assisted 6-endo cyclization, and expansion reaction of tetrahydropyranyl rings to oxepanes to forge the polycyclic architecture of the target molecule.",10.1021/ol9017408,2009-09-04,0.6064856449209629
Organic Letters,"Stereoselective Preparation of (<i>E</i>)-(1,2-Difluoro-1,2-ethenediyl) Bis[tributylstannane] and Stereospecific Synthesis of (<i>E</i>)-1,2-Difluorostilbenes","[reaction: see text]. The novel bisstannane (E)-(1,2-difluoro-1,2-ethenediyl) bis[tributylstannane] 2 was stereoselectively prepared in a high overall yield through a sequential synthetic route from chlorotrifluoroethylene 1. The synthetic application of this novel bisstannane 2 was exemplified in the Pd(PPh3)4/CuI-catalyzed cross-coupling reactions with aryl iodides, yielding (E)-1,2-difluorostilbenes 3 in moderate to high yields.",10.1021/ol025686+,2002-03-29,0.6064822335201172
Journal of Organic Chemistry,"A New Route to Methyl (<i>R,E</i>)-(−)-Tetradeca-2,4,5-trienoate (Pheromone of<i>Acanthoscelides</i><i>obtectus</i>) Utilizing a Palladium-Catalyzed Asymmetric Allene Formation Reaction","[reaction: see text] A formal total synthesis of the sex attractant of male dried bean beetle, methyl (R,E)-(-)-tetradeca-2,4,5-trienoate, was achieved by a new efficient route utilizing the Pd-catalyzed asymmetric allene synthesis reaction. It was found that the atropisomeric biaryl bisphosphine (R)-segphos showed better enantioselectivity than (R)-binap in the Pd-catalyzed reaction for preparing alkyl-substituted axially chiral allenes.",10.1021/jo050684z,2005-06-08,0.6064762198138982
Synlett,New Efficient Synthetic Routes to Enantiomerically Pure Fluoroalkyl (Arylsulfinyl)methyl Imines and Amines,"All articles of this category The synthesis of N -aryl and N -alkyl fluoroalkyl (arylsulfinyl)methyl imines ( R )- 1 , new chiral and enantiomerically pure fluoro- and nitrogen substituted templates, has been efficiently accomplished by two different methods, both consisting in two steps, from cheap fluoroacetic acids or esters. Route A consists in the addition of N -substituted trifluoro- and chlorodifluoroacetimidoyl chlorides 2 to α-lithium methyl- p -tolylsulfoxide ( R )- 3 , and Route B in the aza-Wittig reaction between N -aryl iminophosphoranes 4 and γ-fluoro-β-ketosulfoxides ( R )- 5 . Preliminary investigations on the reduction of 1 to the corresponding fluoroalkyl (arylsulfinyl)methyl amines 6 , and the exploitation of this method in the synthesis of 3,3,3-trifluoroalanine ( R )- 8 is described. fluoroacetimidoyl chlorides - aza-Wittig - sulfoxides - imines - trifluoroalanine",10.1055/s-1996-5593,1996-09-01,0.6064692622132143
European Journal of Organic Chemistry,"Synthesis of 5-Methylbenzo[b]thieno[2,3-c]isoquinolines and5-Methylbenzo[b]seleno[2,3-c]isoquinolines","5-Methylbenzo[b]thieno[2,3-c]isoquinolines and 5-methylbenzo[b]seleno[2,3-c]isoquinolines 11b,c have been prepared by Bischler-Napieralski cyclization of 2-acetamido-3-phenylbenzo[b]heteroarenes.",10.1002/1099-0690(200004)2000:7<1353::aid-ejoc1353>3.0.co;2-a,2000-04-01,0.6064619989700665
Organic Process Research & Development,Synthesis of the Pleuromutilin Antibiotic SB-268091: A New Practical and Efficient Synthesis of Quinuclidine-4-thiol,A synthesis of the pleuromutilin antibiotic SB-268091 is described which includes a new and improved route to the quinuclidine-4-thiol ligand. This chemistry has been run on multikilo scale and involved a reductive double debenzylation using sodium in liquid ammonia. Alternative conditions have been developed to prepare quinuclidine-4-thiol which avoid the use of sodium in liquid ammonia. The generality of this process to prepare differentially S -protected quinuclidine-4-thiols is also discussed and exemplified by the preparation of a range of analogues.,10.1021/op300263w,2012-11-05,0.6064597007599175
Journal of Organic Chemistry,Trimethylene Methane Dianion Equivalent for the Asymmetric Consecutive Allylation of Aldehydes: Applications to Prins-Driven Macrocyclizations for the Synthesis of Bryostatin 1 and Analogues,"We report a one-step (one-flask) generation and reaction of a bifunctional allylating reagent, a trimethylene methane dianion equivalent, that provides a route for the asymmetric 2-(trimethylsilylmethyl) allylation of aldehydes. The product of the first aldehyde allylation process is then set to engage in a second separate aldehyde allylation, providing an improved Prins macrocyclization strategy both for the scalable synthesis of bryostatin 1 and for the total synthesis of a new potent bryostatin analogue.",10.1021/acs.joc.2c02047,2022-11-15,0.6064568057167686
Journal of Organic Chemistry,Synthesis of Etrasimod (APD334): Al<sub>2</sub>O<sub>3</sub>-Promoted Decarboxylative Rearrangements of Cyclopentenones with Stereochemical Inversion,"This study presents an efficient synthesis pathway for etrasimod, starting from (+)- cis -4-acetoxy-2-cyclopenten-1-ol, yielding 5.6% overall with 98% enantiomeric excess. The crucial intermediate, (4 R )-anilinocyclopent-2-enone, was derived from the ( S )-alcohol/isocyanate adduct through a concerted, Al 2 O 3 -promoted decarboxylative rearrangement, which inverted the configuration. A tetracyclic fused lactam was formed via a one-pot acylation-Michael addition, followed by keto α-arylation. Subsequent removal of the oxo group facilitated the synthesis of cyclopenta[ b ]indol-3-ylacetic acid through a series of reactions, including methanolysis, indoline oxidation, and hydrolysis.",10.1021/acs.joc.4c01463,2024-08-16,0.6064539553357382
Angewandte Chemie International Edition,General Entry to Aspidosperma Alkaloids: Enantioselective Total Synthesis of (−)‐Aspidophytine,"A general approach toward the asymmetric total synthesis of various aspidosperma alkaloids includes the combination of a C-H bond activation with a Heck-type coupling, and the stereo-controlled formation of piperidine and pyrrolidine rings as key steps. The feasibility of this approach was demonstrated with the total synthesis of aspidophytine in 18 steps from 4,4-disubstituted cyclohexanedione and 2,3-dimethoxyaniline.",10.1002/anie.201302442,2013-04-22,0.606440387905827
Tetrahedron,An asymmetric synthesis of the pentacyclic core of stemofoline,,10.1016/j.tetlet.2013.01.110,2013-02-01,0.6064338301269561
European Journal of Organic Chemistry,Synthesis of the C4–C17 Fragment of Saliniketals A and B,"Abstract A highly stereoselective synthesis of the C4–C17 fragment of saliniketals A and B was completed. The key steps in this synthesis included a syn ‐aldol reaction mediated by a boron enolate and a double diastereodifferentiating aldol reaction mediated by a titanium enolate. Moreover, a substrate‐controlled Grignard reaction, an intramolecular Wacker‐type cyclization and a Seyferth–Gilbert homologation provided the C4–C17 fragment of saliniketals A and B in 16 steps and with a 7 % overall yield.",10.1002/ejoc.201300012,2013-03-18,0.6064334905921028
Synlett,Concise Total Synthesis of (±)-Crinine,The concise total synthesis of (+/-)-crinine was accomplished in 24% overall yield and eleven steps starting from an easily available allylic alcohol. The key step of the current synthesis involved the NBS-promoted semipinacol rearrangement reaction of allylic alcohols. The hydroindole skeleton with the sterically congested quaternary carbon center was established concisely by utilizing this semipinacol rearrangement followed by a combination of intramolecular aldol and aza-Michael reactions.,10.1055/s-0029-1218296,2009-10-13,0.606433330252156
Angewandte Chemie International Edition,Asymmetric Autocatalysis Enables an Improved Synthesis of Efavirenz,Priming the pump: An asymmetric autocatalytic zinc acetylide addition employs catalytic amounts of the enantiomerically pure product as part of a chiral cocktail. This new strategy enables an improved synthesis of a key precursor to efavirenz (see scheme).,10.1002/anie.201006689,2011-03-01,0.60642746495654
European Journal of Organic Chemistry,"Synthesis of 2‐, 3‐, and 4‐Substituted Pyrido[2,3‐<i>b</i>]indoles by C–N, C–O, and C–C(sp) Bond Formation","Abstract The synthesis of 2‐, 3‐, and 4‐substituted α‐carbolines is described starting from the corresponding chloropyrido[2,3‐ b ]indoles by Buchwald–Hartwig and Sonogashira cross‐coupling reactions. Regioselective Sonogashira reactions on 2,4‐dichloropyrido[2,3‐ b ]indoles are also presented as an efficient route to unsymmetrically 2,4‐disubstituted α‐carbolines.",10.1002/ejoc.201000795,2010-10-20,0.6064260655992872
Tetrahedron,"An intramolecular 4+3 cycloaddition-vinylogous grob fragmentation route to a tricyclo[6.3.0.02,4] undecene ring system",,10.1016/0040-4039(93)89013-g,1993-01-01,0.6064072022797435
Tetrahedron,Toward the synthesis of tulearin C: stereoselective synthesis of the C1–C18 macrolactone core,,10.1016/j.tetlet.2013.02.052,2013-03-13,0.6064038157343555
Angewandte Chemie International Edition,A Short Synthesis of (±)-13-Deoxyserratine,"A short and efficient total synthesis of (±)-13-deoxyserratine (3) features a highly stereoselective intramolecular Pauson–Khand reaction of 1 and a cascade of radical cyclizations starting with the amidyl radical 2. The desired alkaloid 3 was thus obtained in ten steps in an overall yield of 12 %. THP=tetrahydropyranyl, TBS=tert-butyldimethylsilyl.",10.1002/1521-3773(20020517)41:10<1783::aid-anie1783>3.0.co;2-i,2002-05-17,0.6063918164384646
Tetrahedron,"Theonellamide F Synthetic Studies. Stereoselective Synthesis of (3S, 4S, 5E, 7E)-3-Amino-8-(4-bromophenyl)-4-hydroxy-6-methyl-5,7-octadienoic acid (Aboa)",,10.1016/0040-4039(92)88133-p,1992-04-01,0.6063863149497174
Tetrahedron,"Corrigendum to “Highly diastereoselective synthesis and template manipulation of the thiazolo[2,3-a]isoindolin-1-one ring system”",,10.1016/s0040-4039(01)02058-5,2002-01-01,0.6063832749905027
Tetrahedron,"Highly diastereoselective synthesis and template manipulation of the thiazolo[2,3-a]isoindolin-1-one ring system",,10.1016/s0040-4039(00)00128-3,2000-03-01,0.6063832749905027
Journal of Organic Chemistry,Total Synthesis and Cytotoxicity Evaluation of Pareitropone and Analogues,"A concise synthesis of pareitropone by oxidative cyclization of a phenolic nitronate is delineated. The use of TMSOTf as an additive to promote the facile formation of a strained norcaradiene intermediate provides convenient access to highly condensed multicyclic tropones in high yields. This synthesis is modular, efficient, and scalable, highlighting the synthetic utility of radical anion coupling reactions in annulation reactions. This work is discussed in the context of total syntheses of the tropoloisoquinoline alkaloids. Also included are the preparation of several congeners and a brief description of their biological activities.",10.1021/acs.joc.4c00236,2024-04-17,0.6063778914741793
Organic Process Research & Development,Reduction of an Enaminone:  Synthesis of the Diamino Alcohol Core of Ritonavir,"The reduction of (5 S )-2-amino-5-dibenzylamino-4-oxo-1,6-diphenylhex-2-ene was optimized for diastereoselectivity and overall conversion to (2 S,3 S,5 S )-5-amino-2-dibenzylamino-3-hydroxy-1,6-diphenylhexane ( 2a ). A two-step reduction sequence is described wherein the enamine is reduced with a borane-sulfonate derivative followed by reduction of the resulting ketone with sodium borohydride. The desired 2a was obtained with 84% diastereoselectivity and an acyclic 1,4 stereoinduction ratio of 14:1. This methodology has been used to produce multikilogram quantities of the diamino alcohol core of Ritonavir and should be general to the synthesis of related diamino hydroxyethylene isosteres.",10.1021/op9802071,1999-01-08,0.606374418295295
Tetrahedron,α-Methylene lactones. VII. A facile route to an oxygenated α-methylene-γ-butyrolactone,,10.1016/s0040-4039(01)91939-2,1974-01-01,0.6063685245154593
Tetrahedron,A facile route to -muscone,,10.1016/s0040-4039(00)91749-0,1976-07-01,0.6063685245154593
Synthesis,A Facile Route to 2-Noradamantanone via 4-Protoadamantanone,,10.1055/s-1980-28964,1980-01-01,0.6063685245154593
Tetrahedron,Sulfonylmercuration of conjugated dienes. A facile route to allyl- and dienyl-sulfones,,10.1016/s0040-4039(00)88957-1,1985-01-01,0.6063685245154593
Tetrahedron,A facile route to perylenequinone,,10.1016/s0040-4039(00)80060-x,1988-01-01,0.6063685245154593
Tetrahedron,A facile route to homochiral sulfoxides,,10.1016/s0040-4039(01)80467-6,1989-01-01,0.6063685245154593
Tetrahedron,Total synthesis of the ionophore antibiotic ionomycin. Asymmetric synthesis of the C1_C10 and C11_C16synthons.,,10.1016/s0040-4039(00)84163-5,1986-01-01,0.6063637669978019
Tetrahedron,Total synthesis of the ionophore antibiotic ionomycin. Asymmetric synthesis of the C1-C10 and C11-C16 synthons,,10.1016/s0040-4039(86)80034-x,1986-01-01,0.6063637669978019
Journal of Organic Chemistry,"Preparation of a 24-Nor-1,4-dien-3-one Triterpene Derivative from Betulin:  A New Route to 24-Nortriterpene Analogues<sup>1</sup>","A new route to 24-nortriterpene derivatives with 2-hydroxy-Delta(1,4)-cyclohexadien-3-one A-rings from triterpene precursors has been demonstrated beginning with betulin to prepare derivatives of betulinic acid. The key steps in the transformation are a Suárez cleavage of the A-ring with a subsequent SmI(2)-mediated pinacol-type coupling to reclose the A-ring following removal of the C-24 carbon by oxidative cleavage.",10.1021/jo010929h,2002-04-11,0.6063621371558794
Synthesis,Synthesis of Fused Oxepane HIV Integrase Inhibitor MK-1376,"Controlling the absolute and relative stereochemistry of a seven-membered oxepane in the formation of HIV integrase inhibitor MK-1376 was accomplished through a strategy involving the use of asymmetric allylation and stereoconvergent, substrate-directed installation of an amine fragment. Surprising reactivity was demonstrated during the asymmetric allylation in which the allyl-pyrimidone product was formed reversibly. The stereoconvergent amine addition was accomplished through an elimination/addition sequence involving a quinone methide reactive intermediate, and nucleophilic trapping of the reactive quinone methide intermediate with methylamine. This novel approach delivered MK-1376, offering 100-fold greater productivity and 50-fold less waste than the initial synthetic chemistry route.",10.1055/s-0040-1707994,2020-03-16,0.6063614208617459
Synlett,Total Synthesis of Pterosines B and C via a Photochemical Key Step,"A total synthesis of pterosines B and C is reported. Starting with a fourfold substituted benzene derivative, the introduction of the remaining substituents is mainly based on Sonogashira couplings followed by different transformations of the ethyne moiety. The key step is a photochemical ring-closure of an α-mesyloxy ­ketone forming the 1-indanone skeleton.",10.1055/s-2006-944190,2006-06-01,0.6063609596865632
Angewandte Chemie International Edition,First Desymmetrization of a Centrosymmetric Molecule in Natural Product Synthesis: Preparation of a Key Fragment in the Synthesis of Hemibrevetoxin B,Exploitation of molecular symmetry can greatly improve the efficiency of syntheses. The symmetry embedded in the centrosymmetric AB dioxepane fragment of hemibrevetoxin B was exploited for the first time in the preparation of an established intermediate in its total synthesis. Desymmetrization of the centrosymmetric diepoxide 1 by enantioselective epoxide hydrolysis followed by acetonization gave the known synthetic intermediate 2.,10.1002/1521-3773(20011105)40:21<4082::aid-anie4082>3.0.co;2-t,2001-10-31,0.606359184184333
European Journal of Organic Chemistry,A Glycal Approach to the Synthesis of Steviamine Analogues,"Abstract The synthesis of two new stereoisomers of steviamine, namely 1,8a‐di‐ epi ‐(+)‐steviamine and 2,3‐di‐ epi ‐(–)‐steviamine, is reported, starting from tri‐ O ‐benzyl‐ D ‐glucal. The key step in the synthesis was a modified Julia olefination of a 2‐formyl‐polyhydroxy‐pyrrolidine with a sulfone derived from ethyl acetoacetate. Glycosidase‐inhibition studies revealed that 2,3‐di‐ epi ‐(–)‐steviamine is a selective inhibitor of α‐galactosidase.",10.1002/ejoc.201402943,2014-09-24,0.6063556777014936
Tetrahedron,Synthesis of a β-GlcN-(1→4)-MurNAc building block en route to N-deacetylated peptidoglycan fragments,,10.1016/j.tetlet.2009.12.124,2009-12-30,0.6063520610594229
Organic Letters,Asymmetric Total Synthesis of (−)-Awajanomycin,"The first asymmetric total synthesis of the unnatural enantiomer of cytotoxic awajanomycin (1) is reported. The synthetic approach features first a convergent strategy using the cross-olefin metathesis reaction to link the lipid side chain 2 and the piperidinone core structure 3. The second feature of the synthesis resides on the construction of segment 3 from the building block 5 via a three-component tandem reaction on the mixed imide 12. Through this work, the stereochemistry at C-11 and the absolute configuration of awajanomycin were established as 3R,5R,6S,8S,11S.",10.1021/ol902180t,2009-10-20,0.6063478064646636
Journal of Organic Chemistry,Synthesis of α-Substituted β-Amidophosphines by Diastereoselective Alkylation. A New Access to Chiral Ligands for Asymmetric Catalysis,"Chiral beta-amidophosphine boranes 7a-f can be diastereoselectively alkylated, using O-protected amino-alcohols as chiral inducers, to furnish alpha-substituted beta-amidophosphine boranes 8a-f and 9-12 with up to 72% diastereoisomeric excess. Selective deprotection afforded optically pure carboxylic derivative 13 which is a key intermediate for the synthesis of various potential chiral ligands for asymmetric catalysis.",10.1021/jo0155759,2001-07-19,0.6063394830296409
Organic Letters,Catalytic Asymmetric Synthesis of the Pentacyclic Core of (+)-Citrinadin A,"The synthesis of the pentacylic core of (+)-citrinadin A is described. Our strategy harnesses the power of palladium-catalyzed trimethylenemethane chemistry (Pd-TMM) to form the key spirooxindole motif in a catalytic, asymmetric fashion. Upon the conversion of this spirooxindole to a vinyl epoxide electrophile, the piperidine ring is directly added via a diastereoselective metalation followed by an S N 2′ addition. The final ring of the pentacyclic core is then formed through an intramolecular S N 2 displacement of the resulting activated alcohol.",10.1021/acs.orglett.1c01389,2021-06-11,0.6063388524234937
Organic Process Research & Development,Comparison of Large-Scale Routes to Manufacture Chiral <i>exo</i>-2-Norbornyl Thiourea,"Two routes aimed at the manufacture of chiral exo -2-norbornyl thiourea ( 1 ) on large scale are described. The first approach involves five chemical steps and hinges on a classical resolution via diastereomeric salt formation. The synthesis utilizes amine 2 as the resolution handle. The second approach includes two chemical steps and a chiral chromatography of (±)- 1 . Despite the larger initial investment necessary to acquire the chiral stationary phase used in the chromatographic approach, the shorter reaction sequence and efficiency of the chromatographic separation make the second route a more attractive option for long-term applications.",10.1021/op9002328,2009-12-08,0.6063356649504401
Tetrahedron,"A stereospecific route to functionalized alkenes from tetrahydrofurfurylic acetates, synthesis of pheromones",,10.1016/0040-4039(91)80688-3,1991-06-01,0.6063338112095789
Journal of Organic Chemistry,Concise and Convergent Enantioselective Total Syntheses of (+)- and (−)-Fumimycin,The concise and convergent total syntheses of (+)- and (−)-Fumimycin have been achieved by taking advantage of strategies for the asymmetric aza-Friedel–Crafts reaction of a highly substituted hydroquinone and N -fumaryl ketimine generated from the corresponding dehydroalanine. The enantiomerically pure natural product and its enantiomer were prepared in seven steps and 22% overall yield by employing both enantiomers of a BINOL-derived chiral phosphoric acid (CPA) catalyst.,10.1021/acs.joc.9b02020,2019-09-03,0.606329454466842
Tetrahedron,A convenient and concise synthesis of a key lactone intermediate in milbemycin chemistry,,10.1016/s0040-4039(00)78370-5,1994-10-01,0.6063269587139245
Journal of Organic Chemistry,Enantiospecific Synthesis of Trisubstituted Butyrolactone Natural Products and Their Analogs,"A general methodology for the synthesis of highly substituted butyrolactones in enantiomerically pure form has been developed. The application of this process in a highly efficient synthesis of lactone natural products blastmycinone (1), NFX-2 (2), antimycinone (3), and NFX-4 (4) and two lipid metabolites (5, 6) are described. Additionally, the total synthesis of 5-epi-blastmycinone (22), 5-epi-NFX-2 (21b), 5-epi-NFX-4 (21c), and lipid metabolite analogs (19, 20) are also described. The overall yields for the target molecules are the highest reported so far in the literature.",10.1021/jo961171i,1996-01-01,0.6063256056458832
Journal of Organic Chemistry,Total Synthesis of (+)-Hygrine via Asymmetric Phase-Transfer Catalytic Alkylation,The first enantioselective synthesis of (+)-hygrine (1) is reported. 1 was obtained in 12 steps with 29% overall yield and 97% ee via asymmetric phase-transfer catalytic alkylation and ring-closing metathesis as key steps. The absolute configuration of (+)-hygrine could be directly confirmed as R.,10.1021/jo061108l,2006-07-28,0.6063248266109614
Organic Letters,Facile Synthesis of Polyamide Dendrimers from Unprotected AB<sub>2</sub> Building Blocks,"[structure: see text]. A fast, inexpensive, and highly efficient synthesis of aromatic polyamide dendrimers without the need for protection and deprotection steps has been developed. Dendrons and third-generation polyamide dendrimers were easily prepared by a convergent approach involving activation of a focal point with thionyl chloride, followed by condensation with unprotected AB2 building blocks.",10.1021/ol035595s,2003-10-01,0.6063213210485858
Tetrahedron,New catalytic route for the synthesis of an optically active tetralone-derived amine for rotigotine,,10.1016/j.tetlet.2016.01.060,2016-02-01,0.6063207405575183
Organic Letters,A Synthesis of the Carbocyclic Core of Maoecrystal V,"An approach toward the synthesis of the complex polycyclic diterpene maoecrystal V (1) is described. Construction of the advanced tetracyclic core structure (i.e., 19) was achieved in 13 steps from 3,3-dimethylcyclohexanone (6) by employing a stereoselective Nazarov cyclization followed by a Diels-Alder reaction to forge the two contiguous quaternary stereocenters.",10.1021/ol101025r,2010-06-03,0.6063188060533792
European Journal of Organic Chemistry,Stereocontrol with Lithium Trimethylzincate toward Gibberellin Synthesis,"Abstract Substrate control in target‐oriented synthesis is generally important in establishing the required stereogenic center rather than reagent control. During the course of the total synthesis toward Gibberellin A 3 ( 1 ), a model compound ( 21 ) as the A‐ring of 1 was accomplished in five overall steps with an overall yield of 15 %, starting from furfural through conjugate addition of lithium trimethylzincate to oxabicyclo[2.2.1]heptadienedicarboxylic ester ( 2 ) as the key step. Relative to more common lithium dimethylcuprate or aluminum reagents, this zincate complex showed a complete selectivity with higher reactivity than with other simple enone compounds. The incoming methyl group was 100 % selective from the ring oxygen side of 2 , and the enolate intermediate can be protonated stereoselectivly without the bridge‐oxygen‐ring opening.",10.1002/ejoc.201200156,2012-03-02,0.6063125254799994
Tetrahedron,A new synthesis of 6-chloro-2-methyl- and 6-chloro-2- ethyl-5-methyl-4(3H)-pyrimidones,,10.1016/s0040-4039(00)61992-5,1968-01-01,0.6063095844612323
Organic Letters,"Stereoselective Synthesis of <i>trans</i>-3-Amino-2,2,4,4-tetramethylcyclobutanol","A highly trans -diastereoselective synthesis of the useful synthon tert -butyl(3-hydroxy-2,2,4,4-tetramethylcyclobutyl)carbamate was accomplished by ketoreductase (KRED) catalysis with ∼98:2 dr. Herein, we describe its development from inexpensive 2,2,4,4-tetramethylcyclobutane-1,3-dione, evolving from a poorly selective and stoichiometric oxime reduction to an efficient sequence of chemo- and biocatalytic reactions. The utility of this process, which also resulted in a 10-fold improvement in process mass intensity (PMI), was demonstrated on scale en route to a fragment of the investigational androgen receptor degrader GDC-2992 .",10.1021/acs.orglett.5c02505,2025-07-24,0.6063080160467178
Organic Letters,First Total Synthesis of Paracaseolide A,"The first total synthesis of the paracaseolide A, a very unusual tetraquinane oxa-cage bislactone recently isolated from the mangrove Sonneratia paracaseolaris, has been achieved. The final step and culmination of the eight-step synthetic sequence is a [4 + 2] dimerization of a 4-hydroxybutenolide, generated by singlet oxygen-mediated oxidation of a furan precursor.",10.1021/ol301481t,2012-06-26,0.6063060791313342
Organic Letters,Facile Synthesis of Fused Oxasapphyrins,"A simple rapid synthetic route is developed to synthesize new fused meso -aryl oxasapphyrins in 8–10% yield using easily accessible 3-benzoylpyrrole as the key precursor. The method involves McMurry coupling of 3-benzoylpyrrole to obtain an E / Z mixture of dipyrroethene, which was subjected to benzoylation followed by NaBH 4 reduction to afford dipyrroethene diol in situ that was then condensed with 16-oxatripyrrane under mild acid-catalyzed conditions to afford fused oxasapphyrins.",10.1021/acs.orglett.9b03690,2019-11-14,0.6063053688902121
Tetrahedron,"The first direct synthesis of α-mangostin, a potent inhibitor of the acidic sphingomyelinase",,10.1016/s0040-4039(01)02137-2,2002-01-01,0.6062904435146158
Journal of Organic Chemistry,New Pyridone Approach:  Total Synthesis of Mappicine Ketone (Nothapodytine B),"A novel synthesis of mappicine ketone, which possesses strong selective activity against the herpes viruses HSV-1 and HSV-2, including those Acyclovir-resistant, and human cytomegalovirus (HCMV) has been efficiently accomplished. The synthesis highlights a new pyridone approach that effectively combines a double, intramolecular Michael addition in a conjugated ester-conjugated amide with oxidation-decarboxylation of the resulting piperidone.",10.1021/jo0003448,2000-07-21,0.6062850775610724
Organic Letters,A New Convergent Route to Aldohexoses from a Common Chiral Building Block,[reaction in text] A diastereocontrolled route to the eight aldohexoses has been developed starting from a common cyclohexanoid chiral building block.,10.1021/ol015733i,2001-04-04,0.6062798883656586
Synlett,New Efficient Synthesis of 1-Aminocyclopropanecarboxylic Acid,"All articles of this category Methyl 2-[bis(methylthio)methyleneamino]acrylate ( 1 ) was efficiently converted into methyl 1-[bis(methylthio)-methyleneamino]cyclopropanecarboxylate ( 3 ) by reaction with diazomethane. This transformation provides a novel and efficient route to 1-aminocyclopropanecarboxylic acid (ACC), which is found in many plants.",10.1055/s-1992-21422,1992-01-01,0.6062746433615476
Organic Letters,"A One-Pot, Two-Step Synthesis of Tetrahydro Asterriquinone E","Bis(indolyl)dihydroxyquinone 2, the tetrahydro analogue of naturally occurring 1a, was synthesized by a novel, expeditious route. The short synthesis was accomplished by treating p -bromanil (3) with 2 equiv of indole 4 in the presence of cesium carbonate in acetonitrile at ambient temperature to provide a 1:1 mixture of the dibromo regioisomers 7 and 8, followed by hydrolysis of the mixture to afford 2 . The synthetic compound 2 was found to inhibit the binding of the Grb2 adapter protein to tyrosine-phosphorylated EGF receptor (IC 50 = 1.2 μM).",10.1021/ol990075b,1999-06-25,0.6062656349277059
Journal of Organic Chemistry,Synthesis and Biological Activity of the C′D′E′F′ Ring System of Maitotoxin,Stereoselective synthesis of the C'D'E'F' ring system of maitotoxin was achieved starting from the E' ring through successive formation of the D' and C' rings based on SmI2-mediated reductive cyclization. Construction of the F' ring was accomplished via Suzuki-Miyaura cross-coupling with a side chain fragment and Pd(II)-catalyzed cyclization of an allylic alcohol. The C'D'E'F' ring system inhibited maitotoxin-induced Ca(2+) influx in rat glioma C6 cells with an IC50 value of 59 μM.,10.1021/jo5005235,2014-05-09,0.6062647636085069
Tetrahedron,The synthesis and isolation of caffeoquinone and caffeoquinone methyl ester,,10.1016/s0040-4039(00)93718-3,1976-01-01,0.6062566953376265
Journal of the American Chemical Society,"Ir-Catalyzed, Stereoselective Total Synthesis of (+)-Rubriflordilactone A","A stereocontrolled asymmetric total synthesis of the Schisandra nortriterpenoid (+)-rubriflordilactone A employing Krische’s Ir-catalyzed 2-(alkoxycarbonyl)allylation for late-stage γ-butenolide formation is described. Additional noteworthy aspects include the integration of Carreira’s Ir/amine dual-catalyzed allylation, Suzuki coupling, and Catellani reaction, resulting in the formation of an indane iodide. The alkylation of lactone 7, followed by RCM, A-ring formation via condensation of the B-ring lactone with Bestmann ylide, and Morken’s Pt-catalyzed diboration/oxidation, facilitates the stereoselective formation of the ABCDEF ring system.",10.1021/jacs.5c05000,2025-05-09,0.6062465045914776
Organic Letters,Nitrenium Ion-Mediated Alkene Bis-Cyclofunctionalization: Total Synthesis of (−)-Swainsonine,"The total synthesis of (-)-swainsonine from 2,3-O-isopropylidene-D-erythrose in 12 steps and an overall yield of 28% is reported. The pivotal transformation in our route to this indolizidine alkaloid is the formation of the pyrrolidine ring and C-8a/8 stereodiad through the diastereoselective, bis-cyclofunctionalization of an γ,δ-unsaturated O-alkyl hydroxamate. This transformation is believed to proceed via the intramolecular capture of an N-acyl-N-alkoxyaziridinium ion generated by the diastereoselective addition of a singlet acylnitrenium ion to the pendant alkene.",10.1021/ol2006117,2011-04-12,0.6062439516548791
Tetrahedron,Stereoselective synthesis of Δ5 -oxonene and its novel ring contraction to Δ4 -oxocene,,10.1016/0040-4039(95)01773-b,1995-11-01,0.6062404854263735
Tetrahedron,Stereoselective Synthesis of Δ5-Oxonene and Its Novel Ring Contraction to Δ4-Oxocene,,10.1016/00404-0399(50)1773b-,1995-11-06,0.6062404854263735
Tetrahedron,A novel stereoselective synthesis of the ring AB podocarpate system,,10.1016/s0040-4039(01)93406-9,1989-01-01,0.6062404854263735
Tetrahedron,Selectfluor™: a novel and efficient reagent for the synthesis of β-hydroxy thiocyanates,,10.1016/j.tetlet.2003.11.102,2003-12-19,0.606240235034566
European Journal of Organic Chemistry,A New Synthetic Route to Unsymmetrical 9‐Arylxanthenes,"Abstract A facile and general three‐step synthetic route towards unsymmetrical 9‐arylxanthenes was developed. The reaction sequence involves nucleophilic substitution of commercially available 2‐fluorobenzaldehydes with arenoxides, Grignard reaction of the resulting 2‐arenoxybenzaldehydes with arylmagnesium bromides, followed by FeCl 3 ‐catalyzed intramolecular diarylmethylation of the resulting carbinols. This strategy was extended to access symmetrical as well as unsymmetrical 9‐arylthioxanthenes.(© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2009)",10.1002/ejoc.200900676,2009-08-20,0.606232984983497
Journal of the American Chemical Society,"Total Synthesis of a Mycobactin S, a Siderophore and Growth Promoter of <i>Mycobacterium Smegmatis</i>, and Determination of its Growth Inhibitory Activity against <i>Mycobacterium tuberculosis</i>","A general total synthesis of mycobactins, represented by a mycobactin S, was achieved by a convergent approach. Two hydroxamic acid residues, 28 and 40b, were prepared from commercially available N α -Cbz- l -lysine via dimethyldioxirane oxidations. Cyclization of hydroxylamine 34 to a seven-membered hydroxamic acid, 35, was mediated by DCC, DMAP, and DMAP·HCl. The use of a [2-(trimethylsilyl)ethoxy]methyl group as a hydroxyl protecting group for N α -Cbz- N ε -hydroxy- N ε -palmitoyl- l -lysine methyl ester ( 28 ) was critical for this synthesis. Biological tests indicated that the synthetic mycobactin S was a potent growth inhibitor of Mycobacterium tuberculosis H37Rv, though it differs in only one stereogenic center from mycobactin T, the siderophore growth promoter of M. tuberculosis .",10.1021/ja963968x,1997-04-01,0.6062327061818059
Tetrahedron,"Effective synthesis of 3-(Benzimidazol-2-yl)-4-hydroxy-2-oxo-1,2-dihydroquinolines",,10.1016/0040-4039(95)01615-o,1995-10-01,0.6062309202358145
Organic Process Research & Development,"Improved Practical Asymmetric Synthesis of α-Alkylmandelic Acids Utilizing Highly Diastereoselective Alkylation of 5-Aryl-2-(1-naphthyl)-1,3-dioxolan-4-ones","A practical method for the synthesis of optically pure α-alkylmandelic acids 1 is described. The present improved robust method involved two reactions: a mild, convenient, stereoselective preparation of chiral cis -5-aryl-2-(1-naphthyl)-1,3-dioxolan-4-ones, 9a − c, and highly diastereoselective alkylation of 9a − c, followed by the hydrolysis.",10.1021/op050263j,2006-03-21,0.606230804188712
Organic Process Research & Development,Development of a Scaleable Process for the Synthesis of a Next-Generation Statin,"This manuscript details the process research and development of a convergent and safe approach to 1 on a multikilo scale. Specific highlights of the process development efforts will be described, including the development of a dehydrogenation method for dihydropyrimidines and a thermochemically safe synthesis of a 1,2,4-aminotriazole fragment. A key feature of the synthesis is the use and optimization of a modified Julia−Kocienski olefination reaction. Specifically, we report an unprecedented dependence of the product olefin geometry on reaction temperature, where an E: Z ratio as high as 200:1 can be obtained. Initial insights into the mechanistic rationale for this observation are also provided. Finally, a purity upgrade sequence via an intermediate crystalline form is highlighted as a method of controlling the final API quality.",10.1021/op100010n,2010-03-04,0.6062259397898887
Tetrahedron,Stereochemical studies of the formation of chiral internucleotide linkages by phosphoramidite coupling in the synthesis of oligodeoxyribonucleotides,,10.1016/s0040-4039(01)81583-5,1984-01-01,0.6062015473824311
Journal of Organic Chemistry,A New Synthetic Approach to the Carbocyclic Core of Cyclopentane-Type Glycosidase Inhibitors:  Asymmetric Synthesis of Aminocyclopentitols <i>via</i> Free Radical Cycloisomerization of Enantiomerically Pure Alkyne-Tethered Oxime Ethers Derived from Carbohydrates,"The synthesis of compounds 6 - 8, derived from 2,3:5,6-bis- O -isopropylidene- d -mannofuranose ( 3 ), and the preparation of products 16 and 17, obtained from 2,3- O -isopropylidene- d -ribose ( 13 ) is reported. The first free radical cyclization of enantiomerically pure alkyne-tethered oxime ethers derived from carbohydrates ( 6, 8, 16, and 17 ) is described. These radical precursors have been submitted to cyclization with tributyl or triphenyltin hydride plus triethylborane to yield, after ring closure, the aminocyclopentitols 9 − 12 and 18 − 20, respectively. These carbocycles have been obtained as mixtures of Z and E vinyltin isomers, but with excellent diastereoselection at the new stereocenter formed during the ring closure. After protodestannylation, only one diastereoisomer was detected and isolated. The absolute configuration at the new stereocenter formed during the carbocyclization has been established by detailed 1 H NMR analysis. The specific transformation of compound 19 (or 20 ) into aminocyclitol 24 is described. Compound 24 is an analogue of the aminocyclopentitol moiety of trehazolin ( 1a ), a known and powerful glycosidase inhibitor of trehalase. From these results, we can conclude that a new method for the asymmetric synthesis of aminocyclitols of biological interest is now available.",10.1021/jo951891+,1996-01-01,0.6061995017291273
Synthesis,A Concise and Modular Three-Step Synthesis of (S)-Verapamil using an Enantioselective Rhodium-Catalyzed Allylic Alkylation Reaction,"A concise and modular asymmetric synthesis of the calcium channel blocker (S)-verapamil is described. This approach employs an enantioselective rhodium-catalyzed allylic alkylation reaction between an α-isopropyl-substituted benzylic nitrile and allyl benzoate to construct the challenging acyclic quaternary stereocenter. The terminal olefin then serves as a convenient synthetic handle for a hydroamination to introduce the phenethylamine moiety, furnishing (S)-verapamil in three steps and 55% overall yield, thus providing the most efficient synthesis of this important pharmaceutical reported to date. Furthermore, given the modular nature of the synthesis, it can be readily modified to prepare structurally related bioactive agents.",10.1055/s-0040-1707390,2020-06-05,0.6061967672006149
Organic Process Research & Development,Synthesis and Optimization of Canagliflozin by Employing Quality by Design (QbD) Principles,"Efforts toward a synthesis and process optimization of canagliflozin 1 are described. Canagliflozin synthesis was accomplished via purified open ring intermediate 12 . The process was optimized by employing quality by design (QbD) methodologies, and a telescopic strategy was executed for the first three and last two steps in a total six-step sequence. Optimization of the Friedel–Craft acylation reaction followed by Lewis acid mediated reductive elimination, n -BuLi mediated C -arylation, and reductive demethoxylation was performed to develop a robust process. These steps were found to be critical; therefore, critical process parameters (CPPs) were identified by employing design of experiment (DoE) methodology. In addition, control strategies for dealing with impurities are described.",10.1021/acs.oprd.7b00281,2017-12-06,0.6061925153448422
Synlett,Pd<sup>2+</sup>-Promoted Cyclization in Gibberellin Synthesis - A New Strategy for C<sub>20</sub>Gibberellin Synthesis,"All articles of this category The pentacyclic compound 7a , possessing the C 20 gibberellin skeleton, is obtained via a 10-step synthetic sequence from 3-ethoxy-2-cyclohexen-1-one ( 2 ); the most interesting steps of the overall conversion involve Pd 2+ -promoted cyclization of the silyl enol ether of 3 , and stereoselective intramolecular Diels-Alder reaction of the substrate 6 .",10.1055/s-1994-22939,1994-01-01,0.6061885876193687
Tetrahedron,Divergent synthesis of pseudoenantiomers for ABC-ring moiety of steroids,,10.1016/j.tetlet.2014.04.018,2014-04-12,0.6061828898066854
Organic Letters,Synthesis of Bicyclo[3.1.0]hexane Derivatives as Conformationally Restricted Analogues of β-Arabinofuranosyl and α-Galactofuranosyl Rings,"A route for the synthesis of bicyclo[3.1.0]hexane-derived conformationally restricted analogues of beta-arabinofuranosyl and alpha-galactofuranosyl rings is described. Advantage is taken of the pseudo-enantiomeric relationship between the two ring systems to develop a route that provides both targets from a single precursor. Key steps include a base-promoted ring contraction of an epoxy ketone obtained from cyclohexane-1,4-dione to give the bicyclo[3.1.0]hexane ring system and a late stage resolution involving esterification with O-acetyl-(S)-mandelic acid.",10.1021/ol703041y,2008-01-30,0.6061778787034475
Organic Letters,Total Synthesis and Structural Confirmation of the Antimalarial Naphthopyrone Lasionectrin,"The total synthesis of lasionectrin, a naphthopyrone metabolite of an Acremonium-like fungus collected in Equatorial Guinea, is reported. Divergent access to four stereoisomers confirmed the natural product to be the enantiomer of the originally proposed structure. Highlights of the synthesis include ring opening of a chiral oxetane using a thiol, a highly E-selective Julia-Kocienski olefination, and a modified Sharpless/Upjohn dihydroxylation. Palladium-catalyzed carbonylative lactonization was used to assemble the fused naphthopyrone ring system.",10.1021/acs.orglett.5b03202,2015-12-09,0.6061752327226902
Tetrahedron,"7,7-Dimethyl-6,8-dioxabicyclo[3.3.0]oct-3-en-2-one as a synthetic equivalent of ketodicyclopentadiene: a new route to (−)-physostigmine, (−)-physovenine, and (−)-aphanorphine",,10.1016/s0040-4039(00)02171-7,2001-02-01,0.6061674325545889
Organic Letters,Enantioselective Total Synthesis of Valeriananoids A−C,"[reaction: see text] The first enantioselective total synthesis of valeriananoids A-C (-)-1-3 is reported starting from the readily available monoterpene (R)-carvone, employing a tandem intermolecular Michael addition-intramolecular Michael addition-alkylation sequence and an electron-transfer-mediated 6-endo-trig cyclization as key steps.",10.1021/ol049341y,2004-06-15,0.6061625739088481
Organic Process Research & Development,"Development of a Quality Controllable and Scalable Process for the Preparation of 7,8-Difluoro-6,11-dihydrodibenzo[<i>b</i>,<i>e</i>]thiepin-11-ol: A Key Intermediate for Baloxavir Marboxil","A novel six-step synthesis of 7,8-difluoro-6,11-dihydrodibenzo[ b, e ]thiepin-11-ol ( 1 ) is described. Starting with 3,4-difloro-2-methylbenzoic acid and using diphenyl disulfide as an ideal sulfur source effectively solve the problems such as harsh reaction conditions, usage of smelly thiophenol, which might restrict the known process from pilot plant application. Large-scale applicability of this new route has been successfully demonstrated on kilogram-scale production to afford 1 with 98.04% purity in 75% overall yield. Meanwhile, the corresponding impurity profile was thus studied in detail and well documented.",10.1021/acs.oprd.9b00389,2019-11-28,0.6061421385923134
Organic Letters,Convergent Synthesis of the <i>ent</i>-ZA′B′C′D′-Ring System of Maitotoxin,"Stereoselective synthesis of the ent-ZA'B'C'D'-ring system of maitotoxin has been accomplished through a convergent strategy utilizing Suzuki-Miyaura cross coupling reaction of ZA'-ring alkylborane and C'D'-ring (Z)-vinyl iodide, and subsequent construction of the B'-ring by reduction of the O,S-acetal.",10.1021/acs.orglett.7b01301,2017-06-01,0.6061246619884328
Synlett,Synthesis of Novel 3-Amino(Hydroxy)methyl-l-fuco-Azafagomines as Leads for Selective Inhibitors of α-l-Fucosidases,The synthesis of 3-substituted L-fuco-azafagomines from D-lyxose is reported. They represent the first example of aza-C-glycosides having a biimino (-NH-NH-) moiety. The key step of the synthesis is the introduction of the hydrazine moiety by reductive hydrazination of a 1-deoxy-ketohexose with tert-butyl carbazate. Their glycosidase inhibitory properties are also reported.,10.1055/s-0029-1219906,2010-05-10,0.606124407756108
Organic Letters,"A New, Iterative Strategy for the Synthesis of Unsymmetrical Polyynes:  Application to the Total Synthesis of 15,16-Dihydrominquartynoic Acid","[reaction: see text] A new iterative strategy for the synthesis of unsymmetrically substituted polyynes has been developed. The starting bromoalkyne is homologated by one acetylene unit through palladium-catalyzed cross-coupling with a TIPS-protected terminal acetylene and a subsequent in situ one-pot AgF-mediated desilylative bromination. The utility of this new synthetic method is demonstrated by its application to the total synthesis of (S)-(E)-15,16-dihydrominquartynoic acid.",10.1021/ol0484963,2004-08-26,0.6061224568919935
Tetrahedron,The convenient route to cd fragment for the synthesis of vitamin D3 relatives,,10.1016/s0040-4039(00)99003-8,1985-01-01,0.6061157460720977
Tetrahedron,Enantioselective protonation/diastereoselective reduction with sodium naphthalenide-acetamide; a new synthesis of chiral trans-2-phenylcyclohexanol,,10.1016/s0040-4039(99)00615-2,1999-05-01,0.6061054415535994
Journal of Organic Chemistry,"Novel, Short, Stereospecific Synthesis of <i>l</i><i>yxo</i>-(2<i>R</i>,3<i>R</i>,4<i>R</i>)-Phytosphingosine and <i>e</i><i>rythro</i>-(2<i>R</i>,3<i>S</i>)-Sphingosine",Lyxo-phytosphingosine and erythro-sphingosine have been elaborated from a common intermediate. The key step in the reaction sequence involves stereo- and regiospecific functionalization of an olefin by intramolecular nucleophilic sulfinyl group participation.,10.1021/jo034157w,2003-08-14,0.6061022698384917
Journal of the American Chemical Society,A New Convergent Strategy for the Synthesis of Calixarenes via a Triple Annulation of Fischer Carbene Complexes,"A new method for the synthesis of unsymmetrical calix[4]arenes is described which involves the reaction of a diyne with a bis-carbene complex of chromium. This synthesis of calixarenes is unique in that it involves the formation of two of the four benzene rings of the calixarene and the macrocyclic ring of the calixarene in the same step. Thus, two of the four benzene rings of the calixarene are identical, but the other two rings may each be different, giving a general method for the synthesis of calixarenes in which there are either two or three differently substituted benzene rings. This protocol gives access to a large family of unsymmetrical calixarenes by the proper choice of arene substitution in the starting diyne and the starting carbene complex. Nine examples are presented in which the yields in the key triple annulation step range from 22 to 41%. The overall yields of calixarenes from commercially available starting materials compare favorably with those from existing methods for the synthesis of unsymmetrical calix[4]arenes.",10.1021/ja0454236,2004-10-09,0.6060869683386028
Journal of Organic Chemistry,A Concise Total Synthesis of the Azaphenanthrene Alkaloid Eupolauramine,"A six-step total synthesis of the azaphenanthrene alkaloid eupolauramine 1 has been achieved using combinational metalation-cyclization tactics. The synthetic route involved first the construction of the azaisoindolinone 9 by aryne-mediated cyclization of he phosphorylated pyridocarboxamide 7 and subsequent dephosphorylation. Metalation of 9 followed by connection of the hydroxybenzyl appendage and E(1)CB anti-elimination allowed the formation of the halogenoarylmethylene azaisoindolinone 4 in the exclusive E-form. Oxidative radical cyclization gave rise to the azaphenanthrene skeleton and regioselective bromination of 3 induced the incorporation of the bromine atom at the 6-position of the azaphenanthrene lactam. Ultimate replacement of the bromine atom of 2 by the methoxy functionality by sequential transmetalation, in situ oxidation, and O-methylation of the phenolic derivative 14 completed the synthesis of the target natural product eupolauramine.",10.1021/jo0105944,2001-11-01,0.6060848952393657
Journal of the American Chemical Society,"Concise Total Syntheses of Palominol, Dolabellatrienone, β-Araneosene, and Isoedunol via an Enantioselective Diels−Alder Macrobicyclization","Concise total syntheses of four members of the dolabellane family of diterpenoid natural products are reported. Key features of the developed route include the first demonstration of an enantioselective, intramolecular Type I Diels-Alder macrobicyclization, the first example of a stereoselective pi-allyl Stille coupling reaction involving a farnesyl-derived intermediate, a powerful new reagent for the formation of dithianes with acid-sensitive molecules, and a unique and highly efficient ring-contraction sequence based on a modified Wolff photochemical rearrangement.",10.1021/ja0576379,2005-12-24,0.6060771669436092
Tetrahedron,"A synthetic route to poly-N,N′-dimethylethylenediamines",,10.1016/0040-4039(92)88177-7,1992-04-01,0.6060697027676357
Tetrahedron,"The pagodane route to dodecahedranes-unsaturated dodecahedranes, protection and deprotection",,10.1016/s0040-4039(00)92326-8,1992-01-01,0.6060634024430942
Organic Letters,Total Synthesis and Assignment of the Double-Bond Position and Absolute Configuration of (−)-Pyrinodemin A,"[structure: see text] The first asymmetric total synthesis of a structurally novel cis-cyclopent[c]isoxazolidine alkaloid, (-)-pyrinodemin A (3), which exhibits potent cytotoxicity, has been accomplished through a highly diastereoselective intramolecular nitrone-olefin cycloaddition reaction as the key step. Thus, it has been found that the hitherto unknown absolute configuration of pyrinodemin A is as indicated in the structural formula 3.",10.1021/ol034700v,2003-07-01,0.6060502869551584
Journal of Organic Chemistry,Total Synthesis of (−)- and (+)-Tedanalactam,"The first stereoselective route providing access to both enantiomers of tedanalactam, a naturally occurring piperidone, has been developed. The stereogenic centers were generated by the use of Sharpless asymmetric dihydroxylation. Tandem oxidation-Wittig reaction and one-pot deprotection, lactamization, and oxirane ring formation are the other key elements.",10.1021/jo901143b,2009-07-09,0.6060425635318776
Tetrahedron,"Nucleosides LXVI. Synthetic studies on nucleoside antibiotics. 4. synthesis of methyl 4-amino-2,3,4-trideoxy-α---hex-2-enopyranosiduronic acid, the carbohydrate moiety of blasticidin s",,10.1016/s0040-4039(00)61812-9,1970-01-01,0.6060346441447514
Tetrahedron,An efficient synthesis of fluorocyclopentenes using fluoroalkylidenecarbenes,,10.1016/j.tetlet.2007.11.019,2007-11-09,0.6060263842945325
Tetrahedron,Efficient synthesis of chlorohydrins using ClCH2MgCl·LiCl,,10.1016/j.tetlet.2012.10.132,2012-11-21,0.6060263842945325
Tetrahedron,Efficient synthesis of isoxazoles and isoxazolines from aldoximes using Magtrieve™ (CrO2),,10.1016/j.tetlet.2009.04.073,2009-04-25,0.6060263842945325
Tetrahedron,Thermally-induced ring contraction as a novel and straightforward route for the synthesis of 2-furyl acetonitrile derivatives,,10.1016/j.tetlet.2013.03.033,2013-03-15,0.6060219782802875
Organic Letters,A Short Total Synthesis of Aureothin and <i>N</i>-Acetylaureothamine,"The total synthesis of the nitrophenyl pyrones, (+/-)-aureothin and (+/-)-N-acetylaureothamine, starting from known 2-ethyl-6-methoxy-3,5-dimethyl-4H-pyran-4-one are described. The key steps involved in the synthesis are the construction of the tetrahydrofuran motif using a palladium-catalyzed cycloaddition and the ruthenium-catalyzed cross-metathesis reaction of an alkenyl boronic ester. [reaction: see text]",10.1021/ol047594l,2005-01-21,0.606005454777773
Synthesis,Diastereodivergent Synthesis of the C9-Cyclopentanone Chiral Building Blocks,"All articles of this category Diastereodivergent synthesis the C9-cyclopentanone chiral building block, serving as the non-tryptamine moiety of the Corynanthe type indole alkaloids and the related natural products, and its diastereomer has been developed from racemic norcamphor by employing lipase-mediated resolution via an allylic acetate intermediate having a bicyclo[3.2.1]octane framework. A potential of the latter diastereomer has been demonstrated by its conversion into (-)-semburin, a monoterpene isolated from Swertia japonica previously and obtained from the C9-block. lipase-mediated kinetic resolution - enantioconvergent synthesis - diastereoconvergent synthesis - enantiodivergent synthesis - diastereodivergent synthesis - chiral building block - ring expansion",10.1055/s-2000-8235,2000-01-01,0.606003998481615
European Journal of Organic Chemistry,Synthesis of the First Selective Irreversible Inhibitor of Neutral Sphingomyelinase,"The sphingolipid ceramide is a candidate second messenger assumed to be involved in fundamental processes such as growth control, inflammation and apoptosis. Many aspects of ceramide-mediated processes remain to be clarified, including the question of which of the different sphingomyelinases is critical for the stimulus-induced ceramide production. Selective inhibitors of the sphingomyelinases are useful tools for clarifying the biological role of these enzymes and, moreover, appear to be interesting motives for the development of pharmacological agents for an experimental therapy of inflammatory diseases. The full synthesis of N-[2-hydroxy-1-(8-oxo-1-oxa-spiro[2.5]octa-4,6-diene-5-ylcarbamoyl)-ethyl] decanamide (2), the first selective irreversible inhibitor of neutral sphingomyelinase, is described and the relevant analytical data are given. The inhibitor 2 was obtained by a five-step synthesis starting from D-serine.",10.1002/1099-0690(200101)2001:1<137::aid-ejoc137>3.0.co;2-#,2000-12-14,0.6060037952653802
European Journal of Organic Chemistry,Synthesis of the First Selective Irreversible Inhibitor of Neutral Sphingomyelinase,"The sphingolipid ceramide is a candidate second messenger assumed to be involved in fundamental processes such as growth control, inflammation and apoptosis. Many aspects of ceramide-mediated processes remain to be clarified, including the question of which of the different sphingomyelinases is critical for the stimulus-induced ceramide production. Selective inhibitors of the sphingomyelinases are useful tools for clarifying the biological role of these enzymes and, moreover, appear to be interesting motives for the development of pharmacological agents for an experimental therapy of inflammatory diseases. The full synthesis of N-[2-hydroxy-1-(8-oxo-1-oxa-spiro[2.5]octa-4,6-diene-5-ylcarbamoyl)-ethyl] decanamide (2), the first selective irreversible inhibitor of neutral sphingomyelinase, is described and the relevant analytical data are given. The inhibitor 2 was obtained by a five-step synthesis starting from D-serine.",10.1002/1099-0690(200101)2001:1<137::aid-ejoc137>3.3.co;2-r,2001-01-01,0.6060037952653802
Tetrahedron,"A practical route to enantiopure 1,2-aminoalcohols",,10.1016/0040-4039(96)00534-5,1996-05-01,0.6059958004589214
Organic Letters,Total Synthesis of Jimenezin via an Intramolecular Allylboration,[structure: see text] An efficient total synthesis of the annonaceous acetogenin jimenezin was achieved. The key steps used were a highly stereoselective intramolecular allylboration to establish the tetrahydropyran ring and an intramolecular Williamson reaction to close the tetrahydrofuran ring.,10.1021/ol0614471,2006-07-25,0.6059957282243735
Journal of Organic Chemistry,"Probing the SAR of dEpoB via Chemical Synthesis:  A Total Synthesis Evaluation of C26-(1,3-dioxolanyl)-12,13-desoxyepothilone B","A practical total synthesis of 26-(1,3-dioxolanyl)-12,13-desoxyepothilone B (26-dioxolanyl dEpoB) was accomplished in a highly convergent manner. A novel sequence was developed to produce the vinyl iodide segment 17 in high enantiomeric excess, which was used in a key B-alkyl Suzuki merger. Subsequently, a Yamaguchi macrocyclization formed the core lactone, while a selective oxidation and a late stage Noyori acetalization incorporated the dioxolane functionality. Sufficient amounts of synthetic 26-dioxolane dEpoB were produced using this sequence for an in vivo analysis in mice containing xenograft CCRF-CEM tumors.",10.1021/jo020180q,2002-10-10,0.6059906235880802
Angewandte Chemie International Edition,Indoloparacyclophanes: Synthesis and Dopamine Receptor Binding of a Novel Arylbioisostere,Fancy drug candidates: The first preparation of indoloparacyclophanes is reported through the use of the Buchwald variant of the Fischer indole synthesis (see scheme). Receptor binding studies clearly demonstrated that the double-layered molecular scaffold can serve as an effective arylbioisostere.,10.1002/1521-3773(20010401)40:7<1283::aid-anie1283>3.0.co;2-#,2001-03-27,0.6059848352756022
Angewandte Chemie International Edition,Indoloparacyclophanes: Synthesis and Dopamine Receptor Binding of a Novel Arylbioisostere,Fancy drug candidates: The first preparation of indoloparacyclophanes is reported through the use of the Buchwald variant of the Fischer indole synthesis (see scheme). Receptor binding studies clearly demonstrated that the double-layered molecular scaffold can serve as an effective arylbioisostere.,10.1002/1521-3773(20010401)40:7<1283::aid-anie1283>3.3.co;2-r,2001-04-01,0.6059848352756022
Angewandte Chemie International Edition,A Divergent Enantioselective Total Synthesis of Post‐Iboga Indole Alkaloids,"Abstract Divergent enantioselective total syntheses of five naturally occurring post‐iboga indole alkaloids, dippinine B and C, 10,11‐demethoxychippiine, 3‐ O ‐methyl‐10,11‐demethoxychippiine, and 3‐hydroxy‐3,4‐secocoronaridine, as well as the two analogues 11‐demethoxydippinine A and D, are presented for the first time. The enantioenriched aza[3.3.1]‐bridged cycle, a common core intermediate to the target molecules, was constructed through an asymmetric phase‐transfer‐catalyzed Michael/aldol cascade reaction. The challenging azepane ring fused around the indole ring and the [3.3.1]‐bridged cycle were installed through an intramolecular S N 2′‐type reaction. These cyclization strategies enabled rapid construction of the [6.5.6.6.7]‐pentacyclic core at an early stage. Highlights of the late‐stage synthetic steps include a Pd‐catalyzed Stille coupling and a highly stereoselective catalyst‐controlled hydrogenation to incorporate the side chain at C 20 with both R and S configurations in the natural products.",10.1002/anie.202008242,2020-07-02,0.6059828459478277
Angewandte Chemie International Edition,Development of the Vinylogous Pictet–Spengler Cyclization and Total Synthesis of (±)‐Lundurine A,"A novel vinylogous Pictet-Spengler cyclization has been developed for the generation of indole-annulated medium-sized rings. The method enables the synthesis of tetrahydroazocinoindoles with a fully substituted carbon center, a prevalent structural motif in many biologically active alkaloids. The strategy has been applied to the total synthesis of (±)-lundurine A.",10.1002/anie.201803702,2018-04-17,0.6059825753914032
Journal of the American Chemical Society,"10-Step, Gram-Scale Total Synthesis of (−)-Bipinnatin J","A concise, scalable total synthesis of (-)-bipinnatin J is disclosed. Commencing from inexpensive starting materials, this marine diterpenoid was fashioned through a convergent synthesis enabled by Ni-electrocatalytic decarboxylative cross-coupling taking advantage of succinate as an ethylene 2-carbon bridge, a unique halogen dance-Zweifel sequence to access a trisubstituted furan, a Ni-mediated 1,6-conjugate addition, and an asymmetric proton transfer.",10.1021/jacs.5c04761,2025-05-06,0.6059811992100166
Organic Letters,Synthesis of (±)-Eusynstyelamide A,"The synthesis of (+/-)-eusynstyelamide A has been accomplished in six steps in 13% overall yield from 6-bromoindole, methyl glycidate, and Boc-protected agmatine. If oxygen is carefully excluded from the reaction, the key NaOH-catalyzed aldol dimerization of the alpha-ketoamide proceeded efficiently to give Boc-protected eusynstyelamide A.",10.1021/ol100896n,2010-05-06,0.6059807401724798
Organic Letters,General and Efficient Strategy for Erythrinan and Homoerythrinan Alkaloids:  Syntheses of (±)-3-Demethoxyerythratidinone and (±)-Erysotramidine,"[reaction: see text] A general and efficient strategy to both aromatic-type and nonaromatic-type erythrinan and homoerythrinan alkaloids has been developed. This approach involves a key two-step sequence, an alkylation of a ketone with various N-substituted iodoacetamides followed by a N-acyliminium ion promoted intramolecular cyclization, and represents one of the shortest routes to erythrinan and homoerythrinan alkaloids. As the application, the formal total synthesis of (+/-)-3-demethoxyerythratidinone and the total synthesis of (+/-)-erysotramidine have been achieved, respectively.",10.1021/ol0607185,2006-05-01,0.6059775578023258
Journal of Organic Chemistry,"Total, asymmetric synthesis of (+)-castanospermine, (+)-6-deoxycastanospermine, and (+)-6-deoxy-6-fluorocastanospermine","Bromination of the dibenzyl acetal of (-)-(1S,4S)-7-oxabicyclo[2.2.1]hept-5-en-2-one ((-)-5) led to (+)-(1S,5S,6S,7S)-6-endo-(benzyloxy)-5-exo-bromo-7-oxabicyclo[2.2.1]hept an-2-one (25). Baeyer-Villiger oxidation of 25 gave 2-O-benzyl-3-bromo-3,5-dideoxy-beta-L-arabino-hexofuranosidurono-6,1-lac tone (26). Methanolysis of 26 afforded the corresponding methyl (methyl alpha-beta-L-arabinofuranosid)uronates (27 + 28). The alpha anomer 27 was reduced with DIBAH into methyl 2-O-benzyl-3-bromo-3,5-dideoxy-beta-L-arabino-hexofuranoside (29). Mesylation of the primary alcohol, followed by treatment with NH3 gave methyl 2-O-benzyl-3,5-6-trideoxy-3,6-imino-beta-L-lyxo-hexofuranoside (32). Acetylation of the amine with ClCH2COCl, acetolysis of the methyl furanoside followed by Arbuzov condensation with (EtO)3P, and then intramolecular Horner-Emmons reaction led to (5S,6S,7S)-7-hydroxy-5-(benzyloxy)-1-azabicyclo[4.3.0]non-3-en-2-one (37). Base-catalyzed hydrolysis of the corresponding epoxide 43 ((1S,6S,7S,8R,8aS)-8-(benzyloxy)-6,7-epoxy-1-hydroxyoctahydroindolizidin -5-one) followed by reduction of the lactam and deprotection of the alcoholic functions afforded (+)-castanospermine ((+)-1). The conversion of (-)-5 into (+)-1 was highly stereoselective, requiring the isolation of 10 synthetic intermediates and with an overall yield of 15.2%. Reduction of 43 with BH3.Me2S or its treatment with HF.Et3N allowed one to prepare readily (+)-6-deoxycastanospermine ((+)-2 and 6-deoxy-6-fluorocastanospermine ((+)-3). The crystal structure of (+)-3 is also reported.",10.1021/jo00006a031,1991-03-01,0.6059763414919513
Angewandte Chemie International Edition,Total Synthesis of (+)‐Machaeriol D with a Key Regio‐ and Stereoselective S<sub>N</sub>2′ Reaction,"A general strategy for the synthesis of hexahydrodibenzopyrans (HHDBPs) is illustrated in the enantioselective total synthesis of (+)-machaeriol D. In the key step, an SN2′ reaction of an aryl cyanocuprate with a silyl enol ether of an optically active α,β-epoxycyclohexanone enabled the construction of the four stereocenters of the natural product with high regio- and stereoselectivity (see scheme; R=methoxymethyl). TMS=trimethylsilyl, TBS=tert-butyldimethylsilyl.",10.1002/anie.200600006,2006-04-28,0.6059715721688596
Tetrahedron,A novel Diels-Alder reaction utilizing 3-chloro-1-methoxybutadiene: a short and convergent synthesis of the 5-lipoxygenase inhibitor RS-43179,,10.1016/s0040-4039(00)85136-9,1986-01-01,0.6059511341899634
Synthesis,"A Concise Stereoselective Total Synthesis of Synargentolide A from 3,4,6-Tri-O-acetyl-d-glucal","A short and highly stereoselective synthesis of the naturally occurring, α,β-unsaturated lactone synargentolide A is described from the chiral starting material 3,4,6-tri-O-acetyl-d-glucal. Key steps of the synthesis are lactol opening, Brown's asymmetric allylation, and a ring-closing metathesis (RCM) reaction.",10.1055/s-0030-1258458,2011-03-03,0.605950283366373
Tetrahedron,Synthetic studies towards phorboxazole A. A convergent synthesis of the C31C46 polyene oxane-hemiacetal side chain,,10.1016/s0040-4039(98)01258-1,1998-08-01,0.6059492747914424
Synlett,Asymmetric Total Synthesis of Streptoglycerides A and B,"Abstract A unified strategy for the asymmetric total synthesis of streptoglycerides A and B has been established and has confirmed their proposed absolute configurations. Key to our strategy is the synthesis of a bicyclic scaffold, employing a gold-catalyzed cascade cyclization of 1,6-diyn-ol operating through a 6-endo/5-exo-dig mechanism and its one-pot dihydroxylation followed trans-glycosylation to forge the central tricyclic core of these natural products. Noyori’s asymmetric transfer hydrogenation of an α, β-acetylenic ketones has been employed to install the key propargyl alcohol center with the desired absolute configuration. The pendant conjugated trans-1,3,5-triene/trans-1,3-diene side chains were introduced from a propanaldehyde unit following [Pd]-catalyzed oxidative dehydrogenation, Takai olefination, and Stille cross-coupling.",10.1055/a-2738-7991,2025-11-04,0.6059456296199699
Organic Letters,Catalytic Enantioselective Synthesis of Adociacetylene B,A catalytic enantioselective total synthesis of adociacetylene B (2) in five steps is reported. The efficiency of this synthesis was enabled by an asymmetric zinc alkynylation catalyzed by the proline-derived ligand (1).,10.1021/ol0615836,2006-08-29,0.605943292060236
Journal of the American Chemical Society,"Highly Selective Synthesis of Halomon, Plocamenone, and Isoplocamenone","Over 160 chiral vicinal bromochlorinated natural products have been identified; however, a lack of synthetic methods for the selective incorporation of halogens into organic molecules has hindered their synthesis. Here we disclose the first total synthesis and structural confirmation of isoplocamenone and plocamenone, as well as the first selective and scalable synthesis of the preclinical anticancer natural product halomon. The synthesis of these inter-halogenated compounds has been enabled by our recently developed chemo-, regio-, and enantioselective dihalogenation reaction.",10.1021/jacs.5b08398,2015-09-23,0.6059424541165926
European Journal of Organic Chemistry,Synthesis of the 5′‐Fluoro‐2′β‐methyl Analogues of Neplanocin,"Abstract Synthesis of the 5′‐fluoro‐2′‐β‐methyl analogues of neplanocin was carried out. Key intermediate cyclopentenone 19 was prepared from methyl α‐ D ‐mannopyranoside by a new approach consisting of ring‐closing metathesis, stereoselective introduction of the 2′‐methyl group, and intramolecular oxyselenenylation of the double bond as representative steps. Subsequent introduction of a fluorine atom at the 5′‐position of 19 was performed by electrophilic fluorination by using Selectfluor",10.1002/ejoc.201100062,2011-03-25,0.6059415644101624
Journal of the American Chemical Society,"Scalable, Stereocontrolled Total Syntheses of (±)-Axinellamines A and B","The development of a simple, efficient, scalable, and stereocontrolled synthesis of a common intermediate en route to the axinellamines, massadines, and palau'amine is reported. This completely new route was utilized to prepare the axinellamines on a gram scale. In a more general sense, three distinct and enabling methodological advances were made during these studies: (1) an ethylene glycol-assisted Pauson-Khand cycloaddition reaction, (2) a Zn/In-mediated Barbier-type reaction, and (3) a TfNH(2)-assisted chlorination-spirocyclization.",10.1021/ja206191g,2011-08-16,0.6059380424932047
Organic Process Research & Development,A Challenging Synthesis of the Highly Functionalized Echinocandin ASP9726: A Successor of Micafungin,"Here, we describe a practical, scalable, and challenging synthesis of the highly functionalized novel echinocandin ASP9726 ( 1 ) starting from the natural product FR901379 ( 3 ), which is a starting material of micafungin ( 2 ). The synthesis includes transformations that address significant synthetic challenges due to the need to control the chemoselectivity of the reactions during modification of the highly functionalized peptide core. In the present study, we discovered an efficient, high-yielding route to ASP9726 ( 1 ) that is suitable for large-scale production. Namely, dehydration of carboxamide ( 14 ) to nitrile ( 15 ) was accomplished by use of EDC·HCl with pyridine. Further, the transformation of nitrile ( 15 ) to primary amine ( 17 ) was conducted via hydrogenation with Sponge Nickel catalyst without decomposition, followed by one-pot debenzylation with Pd/C. Reductive amination between primary amine ( 17 ) with dihydroxyacetone (DHA) was accomplished using 2-picoline/borane complex as a reducing agent in MeOH, yielding 66.6 kg of peptide core unit ( 18 ). After the C 15 H 31 chain cleavage by bioconversion, reductive amination between the core peptide unit ( 4 ) and side chain ( 10 ) was achieved in high yield by making use of tert -butyl amine/borane complex as a reducing agent. Consequently, highly pure ASP9726 ( 1 ) was obtained in a practical manner without using silica gel or ODS column chromatography purification in any step. Overall yield was drastically increased from 0.71% to 13.8% compared to that of the prior synthetic method.",10.1021/op500078y,2014-05-01,0.6059281022221223
Angewandte Chemie International Edition,An Efficient and Concise Enantioselective Total Synthesis of Lactacystin,,10.1002/(sici)1521-3773(19980703)37:12<1676::aid-anie1676>3.3.co;2-k,1998-07-03,0.6059177395791834
Synlett,Synthesis of Spiro[4.5]decan-1-ones: A Formal Synthesis of Acoradienes and Related Sesquiterpenes via Rhodium-catalyzed Claisen Rearrangement/Hydroacylation,"All articles of this category A novel procedure for the synthesis of spiro[4.5]decan-1-ones starting from commercially available substances is described. The key-step is a one-pot combination of Claisen rearrangement of allyl vinyl ethers followed by an intramolecular hydroacylation 1 catalysed by RhCl(cod)(dppe). 2 The intermediate pent-4-enals generated by the initial [3.3] sigmatropic rearrangement exhibit substitution patterns which have previously been described as unsuitable for the rhodium catalysed intramolecular hydroacylation. 3,4 This procedure allows the synthesis of ketone 2 , a key intermediate in the total synthesis of acoradienes and acorones. 5 acoradienes - spirocyclopentannulation - Claisen rearrangement - hydroacylation - transition metal catalysis",10.1055/s-1996-5707,1996-12-01,0.6059142196641781
Tetrahedron,A new one-pot synthesis of all E-retinoic acid via a new enaminodiester synthon,,10.1016/s0040-4039(03)01431-x,2003-07-01,0.6059010332709812
Tetrahedron,Total synthesis of prostaglandin D1 methyl ester and 9-epi-prostaglandin D1 methyl ester,,10.1016/s0040-4039(00)86889-6,1982-01-01,0.6058967766074332
Tetrahedron,α-Bromination of aldoximes. A route to fused azetidines.,,10.1016/s0040-4039(00)95812-x,1987-01-01,0.6058941048508224
Organic Letters,"Synthesis of 2-Phospha[7]helicene, a Helicene with a Terminal Phosphinine Ring","A synthetic strategy toward phosphahelicenes containing a terminal phosphinine ring has been explored. The 4-phenyl-6-methyl-2-phospha[7]helicene was prepared from starting 2-bromobenzo[ c ]phenanthrene in 12% overall yield in 12 steps. The synthetic approach involves introduction of the phosphorus function prior to photocyclization forming the final helicene skeleton, followed by the formation of a phosphorus hexacycle. The structure of the first phosphahelicene with a terminal phosphinine ring was confirmed by X-ray crystallography.",10.1021/acs.orglett.2c01723,2022-06-24,0.6058907043071143
Journal of Organic Chemistry,Benzothiazines in Synthesis. A Formal Total Synthesis of Pseudopteroxazole,"A formal total synthesis of the antitubercular natural product was accomplished. This work was undertaken to address certain stereochemical problems in our initial synthesis. By using an ester group as a surrogate for a methyl group, we were able to intercept a key intermediate in our first synthesis with better selectivity and greater convergence than had previously been the case.",10.1021/jo9009112,2009-06-18,0.6058856779353925
Journal of the American Chemical Society,Total Synthesis of Formamicin,"The enantioselective total synthesis of the cytotoxic plecomacrolide natural product formamicin (1) is described. Key aspects of this synthesis include the efficient transacetalation reactions of MOM ethers 28 and 38 to form the seven-membered formyl acetals 29 and 39, a late-stage Suzuki cross-coupling reaction of the highly functionalized vinyl boronic acid 6 and vinyl iodide 7, a highly beta-selective glycosidation reaction of beta-hydroxy ketone 4 with 2,6-dideoxy-2-iodoglucopyranosyl fluoride 3, and the global desilylation of penultimate intermediate 77 mediated by in situ generated Et(3)N.2HF.",10.1021/ja048493l,2004-07-09,0.605870949788822
Tetrahedron,Synthesis of cycloisodityrosine revisited: A selective ring forming process,,10.1016/s0040-4039(97)10664-5,1998-02-01,0.6058683473380478
Angewandte Chemie International Edition,Total Synthesis of Antascomicin B,"The structurally enticing antascomicin B (1), which exhibits potent immunosuppressant-antagonizing properties, has a complex polyketide structure. Key steps in its enantioselective total synthesis include a transannular catechol-templated Dieckmann reaction to assemble the challenging tricarbonyl functionality and a butanediacetal-directed allylation.",10.1002/anie.200500174,2005-04-01,0.6058639827048353
Organic Letters,A Simple Enantioselective Synthesis of Serratenediol,"A short synthesis of serratenediol is described, which involves a number of powerful key steps including (1) catalytic enantioselective syntheses\nof the phenyl sulfone and acylsilane shown above, (2) their coupling, and (3) further stereoselective cationic cyclizations.",10.1021/ol026337i,2002-07-04,0.6058600292137335
Synlett,Synthetic Studies on Taxoids: Enantioselective Total Synthesis of (+)-Taxusin and (-)-Taxol,"All articles of this category To construct taxane ABC tricarbocycles, a useful methodology including an aldol-like eight-membered B ring cyclization between dienol silyl ethers and acetals was explored. By applying this methodology, the enantioselective total syntheses of (+)-taxusin and (-)-taxol have been achieved, starting from the substrate containing a chiral center at each C1 site, based on AC to ABC strategies. Syntheses of several artificial taxoids are also described. total synthesis - terpenoids - cyclizations - stereoselective synthesis - asymmetric synthesis",10.1055/s-2000-7619,2000-01-01,0.6058449357763732
European Journal of Organic Chemistry,"Design and Diastereoselective Synthesis of C‐2,C‐20‐Diaryl Steroidal Derivatives","Abstract A novel and efficient synthetic strategy to access unique C‐2 substituted steroid analogues 3 and 4 is described. The unusual C‐2 aryl ether analogues 3 were shown to act as virtual antagonists of LRH‐1 and were prepared as single diastereoisomers, employing a fifteen‐step sequence from pregnenolone ( 9 ). The key steps include the stereoconvergent nucleophilic displacement of an epimeric mixture of 3‐keto 2‐bromo steroids, chemoselective carbonylation of an enol triflate and conversion of a thiopyridyl ester into an aryl ketone. The related C‐2 benzyl analogues 4 were prepared in a similar manner.",10.1002/ejoc.201200190,2012-06-06,0.6058415485925172
Organic Letters,Two Total Syntheses of Trigoxyphins K and L,"High Resolution Image Download MS PowerPoint Slide Two total syntheses are presented for trigoxyphins K and L, tricyclic terpenoids from Trigonostemon xyphophylloides . The first proceeds via electrophlic cyclization in A/C-ring substrates to close the B ring at C4–C5 and then 1 O 2 -mediated hydroxybutenolide formation to trigoxyphin L, with Luche reduction leading to trigoxyphin K. The second route develops from tetralone ring expansion to a B/C-ring intermediate that, by one-step O-demethylation–lactonization–isomerization, affords trigoxyphin K and then trigoxyphin L following enolate oxygenation.",10.1021/acs.orglett.3c02796,2023-10-06,0.605835386369065
Angewandte Chemie International Edition,The Total Synthesis of (±)‐Naupliolide: A Tetracyclic Sesquiterpene Lactone,"The first total synthesis of (±)-naupliolide has been achieved. The synthetic method includes a Simmons-Smith cyclopropanation of an allyl alcohol, diastereoselective cleavage of a benzylidene acetal group, radical cyclization of an aldehyde with a cyclopropane ring, and construction of an eight-membered ring by ring-closing metathesis.",10.1002/anie.201600055,2016-02-10,0.6058336386347928
Journal of the American Chemical Society,Bioinspired Diversification Approach Toward the Total Synthesis of Lycodine-Type Alkaloids,"High Resolution Image Download MS PowerPoint Slide Nitrogen heterocycles (azacycles) are common structural motifs in numerous pharmaceuticals, agrochemicals, and natural products. Many powerful methods have been developed and continue to be advanced for the selective installation and modification of nitrogen heterocycles through C–H functionalization and C–C cleavage approaches, revealing new strategies for the synthesis of targets containing these structural entities. Here, we report the first total syntheses of the lycodine-type Lycopodium alkaloids casuarinine H, lycoplatyrine B, lycoplatyrine A, and lycopladine F as well as the total synthesis of 8,15-dihydrohuperzine A through bioinspired late-stage diversification of a readily accessible common precursor, N -desmethyl-β-obscurine. Key steps in the syntheses include oxidative C–C bond cleavage of a piperidine ring in the core structure of the obscurine intermediate and site-selective C–H borylation of a pyridine nucleus to enable cross-coupling reactions.",10.1021/jacs.1c00457,2021-03-17,0.6058291497893119
Tetrahedron,"Synthesis and hydropyrolysis of bis-trimethylsilyl substituted 3-(4H-cyclopenta[def]phenanthrylidene)-1,4-pentadiyne. A new route to corannulene",,10.1016/s0040-4039(00)76957-7,1994-07-01,0.6058278224950046
Organic Letters,Asymmetric Total Synthesis of (−)-(3<i>R</i>)-Inthomycin C,"A short (10 step) and efficient (15% overall yield) synthesis of the natural product (-)-(3 R)-inthomycin C is reported. The key steps comprise three C-C bond-forming reactions: (i) a vinylogous Mukaiyama aldol, (ii) an olefin cross-metathesis reaction, and (iii) an asymmetric Mukaiyama-Kiyooka aldol. This route is notable for its brevity and has the advantage of lacking stoichiometric tin-promoted cross-coupling reactions present in previous approaches. Initial investigations on the biological activity of (-)-(3 R)-inthomycin C and structural analogues on human cancer cell lines are also described for the first time.",10.1021/acs.orglett.8b01370,2018-06-04,0.6058264354500759
Journal of Organic Chemistry,CRTH2 Antagonist MK-7246: A Synthetic Evolution from Discovery through Development,"In this paper, we report the development of different synthetic routes to MK-7246 (1) designed by the Process Chemistry group. The syntheses were initially designed as an enabling tool for Medicinal Chemistry colleagues in order to rapidly explore structure-activity relationships (SAR) and to procure the first milligrams of diverse target molecules for in vitro evaluation. The initial aziridine opening/cyclodehydration strategy was also directly amenable to the first GMP deliveries of MK-7246 (1), streamlining the transition from milligram to kilogram-scale production needed to support early preclinical and clinical evaluation of this compound. Subsequently a more scalable and cost-effective manufacturing route to MK-7246 (1) was engineered. Highlights of the manufacturing route include an Ir-catalyzed intramolecular N-H insertion of sulfoxonium ylide 41 and conversion of ketone 32 to amine 31 in a single step with excellent enantioselectivity through a transaminase process. Reactions such as these illustrate the enabling impact and efficiency gains that innovative developments in chemo- and biocatalysis can have on the synthesis of pharmaceutically relevant target molecules.",10.1021/jo202620r,2012-02-15,0.6058259977083711
Journal of Organic Chemistry,Synthesis of Substituted Bicyclo[2.2.2]octatrienes,"An efficient route to bicyclo[2.2.2]octatriene, barrelene, and substituted versions of this molecule has been developed starting from the benzene equivalent cis -3,5-cyclohexadiene-1,2-diol. Following the Diels−Alder reaction of this molecule with an activated acetylene, conversion of the diol to the final olefin was accomplished through formation of a thiocarbonate intermediate and subsequent reaction with 1,3-dimethyl-2-phenyl-1,3,2-diazaphospholidine (DPD). The synthesis developed allows a variety of barrelenes to be prepared in as few as three steps from commercially available starting materials.",10.1021/jo971039y,1997-12-01,0.6058197432901885
Tetrahedron,Improved procedure for the regiospecific synthesis of 2′-deoxyribonucleosides,,10.1016/s0040-4039(00)97641-x,1990-01-01,0.6058070009783131
Tetrahedron,An improved procedure for the Hofmann carbylamine synthesis of isonitriles,,10.1016/s0040-4039(01)84707-9,1972-01-01,0.6058070009783131
Journal of Organic Chemistry,Efficient Total Syntheses of Phytoalexin and (±)-Paniculidine B and C Based on the Novel Methodology for the Preparation of 1-Methoxyindoles,"A general route to 2-unsubstituted-1-methoxyindoles, based on our methodology for the synthesis of 1-methoxyindoles, is reported. This synthesis renders accessibility to a variety of natural products possessing the said skeleton. A direct synthesis of phytoalexin (1), (+/-)-paniculidine B (2), and (+/-)-paniculidine C (3) is disclosed based on the methodology. The synthesis of paniculidine B (2) has been achieved from aldehyde 10 in only two steps in 88% yield and in five steps from a methoxyindole compound 8 obtained using our earlier methodology.",10.1021/jo040134l,2004-05-26,0.6058034964761081
Synthesis,Preparation of Tetrahydrothienoazocinone Derivatives,"Three regioisomeric thieno[ c ]azocine derivatives were prepared in six steps from bromothiophene carboxylic acids. The reaction sequence started with an esterification with isopropyl alcohol. The resulting esters were submitted to a Heck reaction with tert -butyl acrylate followed by catalytic hydrogenation. Subsequent Dieckmann condensation gave cyclopentathiophenes with a cyclic β-oxo ester motif, which were α-alkylated with phenacyl bromide to furnish 1,4-diketones. The latter were converted in the key step, a bismuth-catalyzed ring transformation with methylamine, yielding the racemic eight-membered ring lactams, that is, tetrahydrothieno[2,3- c ]-, [3,2- c ]-, and -[3,4- c ]azocine derivatives in overall yields of 25%, 16% and 12%, respectively.",10.1055/s-0034-1379976,2015-01-26,0.6057964889765456
Journal of Organic Chemistry,"Synthesis of the Kinase Inhibitors Nintedanib, Hesperadin, and Their Analogues Using the Eschenmoser Coupling Reaction","A novel synthetic approach involving an Eschenmoser coupling reaction of substituted 3-bromooxindoles (H, 6-Cl, 6-COOMe, 5-NO 2 ) with two substituted thiobenzanilides in dimethylformamide or acetonitrile was used for the synthesis of eight kinase inhibitors including Nintedanib and Hesperadin in yields exceeding 76%. Starting compounds for the synthesis are also easily available in good yields. 3-Bromooxindoles were prepared either from corresponding isatins using a three-step synthesis in an average overall yield of 65% or by direct bromination of oxindoles (yield of 65–86%). Starting N -(4-piperidin-1-ylmethyl-phenyl)-thiobenzamide was prepared by thionation of the corresponding benzanilide in an 86% yield and N -methyl- N -(4-thiobenzoylaminophenyl)-2-(4-methylpiperazin-1-yl)acetamide was prepared by thioacylation of the corresponding aniline with methyl dithiobenzoate in an 86% yield.",10.1021/acs.joc.1c01269,2021-07-16,0.6057940445097892
Organic Letters,Expeditious Entry to the Chamigrane Endoperoxide Family of Natural Products,"Several members of the recently reported peroxy chamigrane family of natural products were synthesized via a distereoselective route with a novel facial-selective epoxidation of a spiroundecadiene, a facile epoxide rearrangement, and a Co(II)-mediated silylperoxidation as the key steps. Adaptation of the diastereoselective route to an enantioselective one is also illustrated.",10.1021/ol503603t,2015-01-12,0.6057925473166904
Organic Letters,Asymmetric Synthesis of Rupestonic Acid and Pechueloic Acid,"In this report, the originally proposed rupestonic acid ( 5 ) and pechueloic acid ( 3 ) were efficiently synthesized. The chiral lactone 13, recycled from the degradation of saponin glycosides, was utilized to prepare the key chiral fragment 11 . During the exploration of this convergent assembly strategy, the ring-closing metathesis (RCM), SmI 2 -prompted intermolecular addition, and [2,3]-Wittig rearrangement proved to be effective transformations for the synthesis of subunits.",10.1021/acs.orglett.7b03459,2017-12-06,0.6057906136890322
Journal of the American Chemical Society,"Rapid Construction of Tetralin, Chromane, and Indane Motifs via Cyclative C–H/C–H Coupling: Four-Step Total Synthesis of (±)-Russujaponol F","The development of practical C–H/C–H coupling reactions remains a challenging yet appealing synthetic venture because it circumvents the need to prefunctionalize both coupling partners for the generation of C–C bonds. Herein we report a cyclative C(sp 3 )–H/C(sp 2 )–H coupling reaction of free aliphatic acids enabled by a cyclopentane-based mono-N-protected β-amino acid ligand. This reaction uses inexpensive sodium percarbonate (Na 2 CO 3 ·1.5H 2 O 2 ) as the sole oxidant and generates water as the only byproduct. A range of biologically important scaffolds, including tetralins, chromanes, and indanes, can be easily prepared by this protocol. Finally, the synthetic application of this methodology is demonstrated by the concise total synthesis of (±)-russujaponol F in a four-step sequence starting from readily available phenylacetic acid and pivalic acid through sequential functionalizations of four C–H bonds.",10.1021/jacs.0c12484,2021-01-04,0.6057890890765729
Tetrahedron,Asymmetric synthesis of the Abbott amino dihydroxyethylene dipeptide isostere subunit,,10.1016/0040-4039(96)00874-x,1996-06-01,0.6057845061962471
Tetrahedron,"Asymmetric synthesis of 2-amino-1,4-diols",,10.1016/s0040-4039(00)80283-x,1988-01-01,0.6057845061962471
Tetrahedron,Asymmetric synthesis of β-amino-γ-hydroxysulfoxides,,10.1016/s0040-4039(00)61657-x,1993-01-01,0.6057845061962471
Tetrahedron,"An efficient method for selective amino acid protection of meso-2,2′-diaminodicarboxylic acid: An improved synthesis of FK-156",,10.1016/s0040-4039(00)86924-5,1982-01-01,0.6057813342795221
Journal of the American Chemical Society,A New Organocatalytic Desymmetrization Reaction Enables the Enantioselective Total Synthesis of Madangamine E,"High Resolution Image Download MS PowerPoint Slide The enantioselective total synthesis of madangamine E has been completed in 30 steps, enabled by a new catalytic and highly enantioselective desymmetrizing intramolecular Michael addition reaction of a prochiral ketone to a tethered β,β′ -disubstituted nitroolefin. This key carbon–carbon bond forming reaction efficiently constructed a chiral bicyclic core in near-perfect enantio- and diastereo-selectivity, concurrently established three stereogenic centers, including a quaternary carbon, and proved highly scalable. Furthermore, the pathway and origins of enantioselectivity in this catalytic cyclization were probed using density functional theory (DFT) calculations, which revealed the crucial substrate/catalyst interactions in the enantio-determining step. Following construction of the bicyclic core, the total synthesis of madangamine E could be completed, with key steps including a mild one-pot oxidative lactamization of an amino alcohol, a two-step Z -selective olefination of a sterically hindered ketone, and ring-closing metatheses to install the two macrocyclic rings.",10.1021/jacs.1c12040,2022-01-17,0.6057709612747642
Organic Process Research & Development,Large-Scale Synthesis of the Anti-Cancer Marine Natural Product (+)-Discodermolide. Part 2:  Synthesis of Fragments C<sub>1</sub><sub>-</sub><sub>6</sub> and C<sub>9-14</sub>,Kilogram-scale syntheses of fragments C 1 - 6 ( 6 ) and C 9 - 14 ( 4 ) of (+)-discodermolide from common precursor 3 are described. Improved procedures for each step of both fragments were developed by minimizing or eliminating the formation of byproducts that were isolated and characterized in Smith's synthesis.,10.1021/op0341317,2003-12-04,0.6057675646836005
Organic Letters,Convergent Synthesis of the E‘FGH‘ Ring Fragment of Ciguatoxin 1B via an Acetylene Cobalt Complex Strategy,"[reaction: see text] A convergent synthesis of the E'FGH' ring fragment of ciguatoxin has been accomplished through (i) coupling between the E' ring-acetylide and the H' ring-aldehyde, (ii) stereoselective F ring cyclization via an acetylene cobalt complex, (iii) conversion to a carbonyl function, and (iv) reductive hydroxy-ketone cyclization to construct the G ring.",10.1021/ol0256264,2002-03-05,0.6057672946011484
Tetrahedron,"Synthesis and luminescence properties of a new tripode containing 2,2′-bipyrazine subunits: The tris-[(6-methyl-2,2′-bipyrazine-2-yl)methyl]amine",,10.1016/0040-4039(94)02381-k,1995-02-01,0.6057607388683174
Journal of Organic Chemistry,(+)-Zwittermicin A. Rapid Assembly of C9−C15 and a Formal Total Synthesis,"A short, enantioselective synthesis of the C9-C15 portion of (+)-zwittermicin A is reported that exploits directional functionalization of the known hepta-2,5-diyne-1,7-diol by partial reduction of the two triple bonds followed by Sharpless asymmetric epoxidation and boron-directed double ring-opening with sodium azide under Miyashita conditions. Subsequent desymmetrization of the C(2)-symmetric diazidotetraol product converges upon (-)-3--the enantiomer of the key intermediate of our earlier structural proof and synthesis of (-)-zwittermicin A--and constitutes a formal synthesis of (+)-zwitttermicin A.",10.1021/jo901007v,2009-09-11,0.6057587831798472
Organic Letters,Diastereoconvergent Synthesis of <i>trans</i>-5-Hydroxy-6-Substituted-2-Piperidinones by Addition–Cyclization–Deprotection Process,"A diastereoselective one-pot approach to access trans-5-hydroxy-6-substituted-2-piperidinones by an addition-cyclization-deprotection process has been developed, in which the stereogenic center at the C-6 position was solely controlled by α-OTBS group. The utility of this transformation is demonstrated by the asymmetric synthesis of the enantiomer of (-)-CP-99,994.",10.1021/ol5020812,2014-08-01,0.6057554352861597
Synthesis,"Halocyclization and Palladium(II)-Catalyzed Amidocarbonylation of Unsaturated Aminopolypols. Synthesis of 1,4-Iminoglycitols as Potential Glycosidase Inhibitors","All articles of this category Syntheses of optically active 2,5-anhydro-1,4-dideoxy-1,4-imino-D-lyxitol (6) , 1,4,5-trideoxy-1,3-imino-D- lyxo -hexitol (14) , and its N -methyl derivative 15 from achiral divinylcarbinol, via the aminopentenediol 1 , are described using halogen-promoted cyclization and Pd(II)-catalyzed amidocarbonylation as key steps. 2,5,6-Trideoxy-2,5-imini-L- ido -heptitol (23) , a diastereomeric homologue of the naturally occurring pyrrolidine DMDP G , is prepared from D-glucosamine hydrochloride in 7 steps in 19% overall yield. The new compounds 6, 14, 15, and 23 show weak glycosidase inhibition in two cases. aminoalkenepolyols - polyhydroxlated pyrrolidines - glycosidase inhibitors - palladium(II) chloride catalysis - amidocarbonylation",10.1055/s-1997-3183,1997-06-01,0.6057550503887563
European Journal of Organic Chemistry,Total Synthesis of Quebrachamine through Macrolactamization,"Abstract The total synthesis of quebrachamine was achieved through the macrolactamization of cis ‐2‐alkenylated indole 17 , which was prepared by a Sonogashira reaction between indole 5b and piperidine 11 followed by cis ‐hydrogenation. We found that stoichiometric copper(I) iodide limited the undesired Glaser‐type homocoupling of alkyne 11 that would otherwise take place during the Sonogashira coupling. This direct approach allowed the total synthesis in ten linear steps starting from commercially available chemicals. Conditions for the reduction of lactam 19 by lithium aluminiumhydride were adjustable, so that either (±)‐quebrachamine or the analogue (±)‐kopsiyunnanine D was prepared.",10.1002/ejoc.201400064,2014-03-17,0.6057444382875492
Angewandte Chemie International Edition,Total Synthesis and Structural Revision of (−)‐Sodagnitin E,"We report the total synthesis of malabaricane triterpene sodagnitin E, marking the first synthesis of any malabaricane natural product to date. The enantioselective synthesis of two key fragments, followed by their coupling via a Mukaiyama aldol reaction delivered the triterpene framework in a convergent synthesis. A thorough analysis of the synthetic material led to the elucidation of a previously unassigned stereocenter (C17) as well as the reassignment of the configuration at C27. This enabled the structural revision of the relative configuration at the central lactol moiety.",10.1002/anie.202506247,2025-05-12,0.6057266413395469
Synthesis,"Preparation of the I<sub>3</sub> Imidazoline Receptor Antagonist KU14R and Related 2,3-Dihydrobenzo[<b><i>b</i></b>]furan Derivatives","The preparation and characterisation of a series of novel analogues of the imidazoline insulin secretagogue efaroxan, including the I3-receptor antagonist KU14R, are described. Replacement of the imidazoline ring of efaroxan by selected functional groups leads either to loss of activity or to very weak I3-agonist activity in insulin secretion studies. The imidazole analogue KU14R was found to be an I3-antagonist in this assay and useful as a biological tool.",10.1055/s-2001-16079,2002-07-26,0.6057143814771067
Journal of Organic Chemistry,Practical Synthesis and Elaboration of Methyl 7-Chloroindole-4-carboxylate,"A synthesis of a previously unknown indole derivative is presented. The route reported herein allows for the preparation of multihundred gram quantities of material without any chromatographic purification. Conditions are presented for the Pd-catalyzed elaboration of one of the ""diversity generating elements"" of this important pharmacophore.",10.1021/jo026434p,2003-02-08,0.6057122913518596
Organic Letters,A New Efficient Synthesis of Pyranoquinolines from 1-Acetyl <i>N</i>-Aryl Cyclopentanecarboxamides,"A new efficient synthesis of pyrano[2,3-b]quinoline derivatives is developed via the H2SO4-mediated tandem cyclization/ring-opening/recyclization reaction of readily available 1-acetyl N-aryl cyclopentanecarboxamides, during which a novel ring-cleavage fashion of the cyclopentane unit is involved and possible mechanisms are discussed.",10.1021/ol701536q,2007-08-01,0.6057106695184695
Organic Letters,A Diastereoselective Total Synthesis of <i>trans</i>-Trikentrin A: A Ring Contraction Approach,"A new route to obtain the polyalkylated indole (+/-)-trans-trikentrin A was developed. The synthesis of this natural alkaloid features a thallium(III)-mediated ring contraction reaction to obtain the trans-1,3-disubstituted five-membered ring in a diastereoselective manner. Thallium(III) is chemoselective in this rearrangement, reacting with the olefin without oxidation of the indole moiety. Other key transformations are the Bartoli's reaction to construct the heterocyclic ring and a Heck coupling to add the carbons atom that will originate the nonaromatic cycle.",10.1021/ol8023105,2008-10-31,0.6057015114856217
Tetrahedron,Synthesis of [4-(hydroxy)tetrahydrofuran-2-yl]nucleosides as a novel class of uridine phosphorylase inhibitors,,10.1016/0040-4039(94)02421-7,1995-02-01,0.6057010160986078
Tetrahedron,Concise total synthesis of the prolyl endopeptidase inhibitor eurystatin A via a novel Passerini reaction–deprotection–acyl migration strategy,,10.1016/s0040-4039(01)01287-4,2001-09-01,0.6056953664770746
Synlett,Synthetic Approaches to Rapamycin. 3. Synthesis of a C1-C21 Fragment,(opens in new window) Buy Article (opens in new window) Permissions and Reprints (opens in new window) All articles of this category (opens in new window) Key steps in two alternative approaches to the C10-C21 fragments 4 and 17 of the immunosuppressant rapamycin employ catalytic asymmetric allylation and catalytic asymmetric hydrogenation to introduce the first stereogenic centre at C14. Appendage of C1-C9 via trapping of an a -oxoketene intermediate generates the C1-C21 fragment 5 . rapamycin - asymmetric allylation - asymmetric hydrogenation - Heck reaction - immunosuppressant - ketenedithioacetal - α-oxoketene,10.1055/s-1996-5604,1996-09-01,0.605691855059738
Tetrahedron,Improved syntheses of methyl (14E)- and (14Z)-dehydrocrepenynate: key intermediates in plant and fungal polyacetylene biosynthesis,,10.1016/s0040-4039(01)00577-9,2001-06-01,0.6056791070826123
Angewandte Chemie International Edition,Total Synthesis of Dictyodendrins by the Gold‐Catalyzed Cascade Cyclization of Conjugated Diynes with Pyrroles,"In total and formal syntheses of dictyodendrins B, C, E, and F, the key step involved the direct construction of the pyrrolo[2,3-c]carbazole core by the gold-catalyzed annulation of a conjugated diyne with a pyrrole to form three bonds and two aromatic rings. The subsequent introduction of substituents at the C1 (Suzuki-Miyaura coupling), C2 (addition to an aldehyde), N3 (alkylation), and C5 positions (Ullman coupling) provided divergent access to dictyodendrins.",10.1002/anie.201703279,2017-05-31,0.6056769391714495
Synlett,Total Synthesis of Thiangazole,"All articles of this category The total synthesis of thiangazole ( 1 ), a tris-thiazoline- oxazole metabolite isolated from Polyangium spec. , strain PI 3007, is described utilizing the stepwise formation of the thiazoline moieties with ethyl ( R )-2-methyl-cysteine which is obtained by preparative HPLC-separation of the racemic 2-phenylthiazoline derivative 8 followed by acidic hydrolysis.",10.1055/s-1994-22977,1994-01-01,0.6056757944868222
Tetrahedron,Methoxyallene as a starting compound for the synthesis of furan derivatives,,10.1016/s0040-4039(00)78783-1,1976-07-01,0.6056661565528293
Journal of Organic Chemistry,Synthesis of Ribonucleosidic Dimers with an Amide Linkage from <scp>d</scp>-Xylose,"An original and efficient stereocontrolled synthesis of ribonucleosidic homo- and heterodimers has been achieved from inexpensive d-xylose. This successful strategy involved the sequential introduction of nucleobases, using two stereocontrolled N-glycosidation reactions, from a common two-furanoside amide-linked scaffold offering the possibility of obtaining any given base sequence. The pertinence of this approach is illustrated through the preparation of the homodimers UU-34 and TT-35 in 18 steps with an excellent overall yield of more than 10% from d-xylose, while the heterodimer route led to UT-39 in 19 steps with around 10% overall yield.",10.1021/acs.joc.6b01822,2016-10-21,0.6056570882777904
Organic Letters,The First Total Synthesis of (−)-Tamandarin A,"[formula: see text] Tamandarin A (1), a newly isolated natural product similar in structure to didemnin B (2), was shown to be somewhat more active in vitro than 2 against pancreatic carcinoma with an ED50 value 1.5 to 2 ng/mL. We report here the first total synthesis of 1. The key steps include a practical stereoselective synthesis of the Hiv-isostatine unit, high-yielding linear precursor formation, a successful macrocyclization, and coupling of the macrocycle with the side chain to afford tamandarin A (1).",10.1021/ol9910058,1999-09-16,0.6056558103907527
Organic Letters,Syntheses of the Carotane-type Terpenoids (+)-Schisanwilsonene A and (+)-Tormesol via a Two-Stage Approach,"Stereoselective syntheses of terpenoids in a more efficient manner have been a long-term pursuit for synthetic chemists. Herein we describe the two-step, enantiospecific and protecting-group-free synthesis of (+)-schisanwilsonene A from a carotane compound, which was produced in E. coli . We also completed the first enantiomeric synthesis of (+)-tormesol in five steps. The two-stage strategy offers a step- and redox-economical approach to prepare terpene natural products and their analogues.",10.1021/acs.orglett.0c03894,2020-12-29,0.6056531432682055
Tetrahedron,An efficient preparation of protected ribonucleosides for phosphoramidite RNA synthesis,,10.1016/s0040-4039(02)00181-8,2002-03-01,0.6056516434636603
Tetrahedron,A versatile one-pot multicomponent synthesis of novel quinazolinon-2-yl-tetrasubstituted thiophenes,,10.1016/j.tetlet.2010.08.046,2010-08-21,0.6056299389464519
Organic Letters,Scalable Syntheses of Methoxyaspartate and Preparation of the Antibiotic Cystobactamid 861-2 and Highly Potent Derivatives,"An improved scalable synthesis of orthogonally functionalized methoxyaspartate, the chiral hinge region element in cystobactamids, is reported. This improvement sets the stage for the total synthesis of four new cystobactamids along with cystobactamid 861-2, whose antibacterial properties are determined and compared. The cyano derivative of cystobactamide 861-2 shows superior antibacterial activity against Gram-negative bacteria to any natural cystobactamide tested so far.",10.1021/acs.orglett.9b03143,2019-10-10,0.6056287100169869
Organic Letters,Synthesis of a 3-Thiomannoside,"An efficient and straightforward synthesis of a novel 3-thiomannoside derivative (1,2,4,6-tetra-O-acetyl-3-S-acetyl-3-thio-β-d-mannopyranoside) was developed starting from levoglucosenone. A xanthate-thiocarbonate exchange under acidic conditions was the key step for the new C-S bond. The product was obtained enantiospecifically in very good overall yield.",10.1021/acs.orglett.6b00428,2016-04-07,0.6056267592549065
Tetrahedron,"Cladosporol, β-1, 3-glucan biosynthesis inhibitor, isolated from fungus, Cladosporium cladosporioides",,10.1016/0040-4039(95)00061-g,1995-02-01,0.605623805088786
Journal of Organic Chemistry,A New Three-Carbon Synthon for Efficient Synthesis of Benzannelated and 1-(2-Arylethenyl) Heterocycles,"The novel three-carbon synthon 1-(1H-1,2, 3-benzotriazol-1-yl)-3-chloroacetone for the synthesis of benzothiazoles, pyrido[1,2-a]indoles, and styryl-substituted indolizines and imidazo[1,2-a]pyridines is reported. The proposed routes are a general and efficient approach for heterocyclizations followed by benzannelations or attachment of arylethenyl pharmacophores.",10.1021/jo000946r,2000-10-21,0.6056187990679918
Journal of Organic Chemistry,Oxaza Adamantyl Cannabinoids. A New Class of Cannabinoid Receptor Probes,The preparation of C3 oxaza adamantyl cannabinoids has been described starting from phloroglucinol. Straightforward manipulations of the aromatic ring lead to a bromononaflate that is a benzyne precursor and that serves as a common intermediate for the synthesis of diverse C3-substituted tricyclic cannabinoids. Generation of the benzyne in the presence of an oxaza adamantyl amide anion results in efficient and regiospecific addition to C3 of the aromatic ring. This represents an attractive strategy for the synthesis of classical tricyclic cannabinoids that bear a modified aromatic appendage. The oxaza adamantyl cannabinoids that have been prepared represent a new class of ligands for the CB1 and CB2 receptors.,10.1021/jo061352c,2006-08-29,0.6056181981181025
Tetrahedron,"A new synthesis of 1,4-diketones: application to a synthesis is of dihydrojasmone and cis-Jasmone",,10.1016/s0040-4039(01)92035-0,1974-01-01,0.6056173067084794
Synthesis,"One-Step Synthesis of 4-Cyano-3,3-diaryl-5-methyl-2-oxo-2,3-dihydropyrroles through the Benzilic Acid Rearrangement",,10.1055/s-1980-29260,1980-01-01,0.6056148875222014
Tetrahedron,Synthesis of chlorinated 5-hydroxy 4-methyl-2(5H)-furanones and mucochloric acid,,10.1016/0040-4039(95)00638-s,1995-05-01,0.6055980495427182
Synthesis,"An Efficient Synthesis of Phosphonate Derivatives of 1,2-Disubstituted Carbocyclic Purine Nucleosides with a Cyclopentane Ring","The synthesis of phosphonate 1,2-disubstituted carbocyclic nucleosides with a cyclopentane ring is described following two different strategies: inclusion of the phosphonomethyl group before or after coupling of the carbocyclic moiety with the heterocyclic base. The diethyl [(trifluoromethanesulfonyl)oxy]methanephosphonate is the key phosphonylating agent for both the strategies.",10.1055/s-2008-1067166,2008-07-08,0.6055915513389113
Organic Process Research & Development,"Racemic Synthesis of a Key 1,4-Dihydro-2<i>H</i>-spiro[isoquinoline-3,4′-piperidin]-3′-ol Building Block",The synthesis of a key spiroamine building block for a medicinal chemistry program is described. Key innovations were a regioselective epoxide ring opening and a late-stage Pictet–Spengler reaction that was quickly optimized using Design of Experiments.,10.1021/acs.oprd.2c00121,2022-11-08,0.6055913529358614
Tetrahedron,"1,3-Dipolar cycloadditions of nitrile oxides to aryl thiocyanates: a new synthetic route to 5-arylthio-1,2,4-oxadiazoles",,10.1016/s0040-4039(00)94064-4,1983-01-01,0.6055881750541716
Tetrahedron,Synthetic studies toward the development of novel minoxidil analogs and conjugates with polyamines,,10.1016/j.tetlet.2010.02.037,2010-02-12,0.6055856333702734
Journal of the American Chemical Society,Total Synthesis of <i>Pseudomonas aeruginosa</i> 1244 Pilin Glycan via <i>de Novo</i> Synthesis of Pseudaminic Acid,"Pseudaminic acid (Pse) is a nonulosonic acid unique to bacterial species, found as a component of important cell surface glycans and glycoproteins in various pathogenic species, such as the critical hospital threat Pseudomonas aeruginosa . Herein we present the development of a facile and scalable de novo synthesis of Pse and its functionalized derivatives from easily available Cbz- l - allo -threonine methyl ester (16 steps in 11% yield). The key reactions in our de novo synthesis involve the diastereoselective glycine thioester isonitrile-based aldol-type reaction to create the 1,3- anti -diamino skeleton, followed by the Fukuyama reduction and the indium-mediated Barbier-type allylation. Moreover, we have studied the glycosylation of the Pse glycosyl donors and identified the structural determinants for its glycosylation diastereoselectivity, which enabled us to complete the total synthesis of P. aeruginosa 1244 pilin trisaccharide α-5NβOHC 4 7NFmPse-(2→4)-β-Xyl-(1→3)-FucNAc.",10.1021/jacs.7b06055,2017-08-24,0.6055843812043008
Organic Letters,Enantioselective Total Synthesis of (+)-Pepluanol A,"Herein, we report an enantioselective and convergent total synthesis of (+)-pepluanol A, a structurally intriguing Euphorbia diterpenoid natural product featuring a 5/6/7/3-fused tetracyclic skeleton, from known building blocks in 11 steps. The successful strategy relies on a phenyl selenide-mediated Morita–Baylis–Hillman type reaction as a connective step, forging the precursor for the key intramolecular Diels–Alder reaction to construct the congested 5/6/7-tricyclic framework. A diastereoconvergent cascade starting with an acid-induced removal of the C1-MOM protecting group followed by a retro-aldol/aldol reaction resulted in the formation of a single diastereomer. This stereoconvergency allowed for the successful substrate-controlled diastereoselective cyclopropanation of an advanced intermediate to establish the full carboskeleton of (+)-pepluanol A ( 1 ).",10.1021/acs.orglett.2c00961,2022-05-11,0.6055793045169902
Synlett,Concise Asymmetric Synthesis of (+)-Conocarpan and Obtusafuran,"The asymmetric synthesis of three natural products: (+)-conocarpan, both (+)- and (–)- obtusafuran is disclosed. The highlights of the synthesis are the enantioselective hydrogenation of prochiral ketones via dynamic kinetic resolution to afford chiral alcohols. Intramolecular ring closure via either S N Ar reaction or metal-catalyzed C–O bond formation led to the construction of the trans -dihydrobenzofuran core.",10.1055/s-0032-1317704,2012-12-21,0.6055761172548433
Journal of Organic Chemistry,IMDAF Cascade Approach toward the Synthesis of the Alkaloid (±)-Minfiensine,"The total synthesis of the Strychnos alkaloid (±)-minfiensine was achieved via an intramolecular amidofuran Diels-Alder cycloaddition/rearrangement followed by an iminium ion/cyclization cascade sequence. This domino process provides for a rapid access to the unique 1,2,3,4-tetrahydro-9a,4a-iminoethanocarbazole core structure found in the alkaloid minfiensine (2). In this paper, the full account of our synthetic study is described, highlighting the successful application of the cascade sequence to form the A/B/C/D rings of (±)-minfiensine (2) in high yield. A palladium-catalyzed enolate coupling reaction was then used to furnish the final E ring and complete the total synthesis of (±)-minfiensine (2).",10.1021/acs.joc.6b00771,2016-05-23,0.6055661004906918
Synthesis,"Cyclotrimerization of Enaminones: An Efficient Method for the Synthesis of 1,3,5-Triaroylbenzenes",,10.1055/s-2003-44472,2003-01-01,0.6055652855050948
Tetrahedron,An efficient method for the synthesis of gem-difluoroolefins,,10.1016/j.tetlet.2016.12.070,2016-12-26,0.6055652855050948
Tetrahedron,An efficient method for the synthesis of C–C connected phthalocyanine–porphyrin oligomers,,10.1016/j.tetlet.2008.12.059,2008-12-25,0.6055652855050948
Tetrahedron,An efficient method for the synthesis of 4-benzoylthioazetidinones,,10.1016/s0040-4039(00)70633-2,1989-01-01,0.6055652855050948
Organic Letters,Synthetic Study of Rubriflordilactone B: Highly Stereoselective Construction of the C-5-epi ABCDE Ring System,A highly stereocontrolled construction of the C-5-epi ABCDE-ring system of rubriflordilactone B has been developed. The present synthesis features a convergent strategy to construct the C-5-epi AB-ring utilizing Mukaiyama-Michael reaction and forge the CDE ring in one step using intramolecular [2 + 2 + 2] cycloaddition of triynes.,10.1021/acs.orglett.6b00057,2016-02-02,0.6055643289841554
Angewandte Chemie International Edition,"Gold‐Catalyzed One‐Step Construction of 2,3‐Dihydro‐1 <i>H</i> ‐Pyrrolizines with an Electron‐Withdrawing group in the 5‐position: A Formal Synthesis of 7‐Methoxymitosene","What a ring formation! Bicyclic dihydropyrrolizines with an electron-withdrawing group (EWG) at the 5-position are formed in one step from linear azidoenynes under gold catalysis. This novel route involves the use of azide as a nitrene precursor, electronically-controlled regioselectivity, and the generation of destabilized 1-azapentadienium ions and their pericyclic reactions. This method was used for a formal synthesis of 7-methoxymitosene.",10.1002/anie.201203678,2012-07-29,0.6055642079252953
Tetrahedron,"A novel stereospecific route to E and Z-2-substituted-1,2-difluoroethenylstannanes",,10.1016/0040-4039(96)00171-2,1996-03-01,0.6055576230962741
Organic Process Research & Development,"Pilot-Scale Production of Dimethyl 1,4-Cubanedicarboxylate","A scalable process for the preparation of high purity dimethyl 1,4-cubanedicarboxylate ( 3 ) is reported. The work described herein builds on previous synthetic work from this and other laboratories, to provide a reliable process that can be used to prepare multigram quantities of 3 in a partially telescoped, 8 step process, with minimal purification of intermediates.",10.1021/op400181g,2013-11-08,0.6055457828650922
Journal of the American Chemical Society,A Convergent Three-Component Total Synthesis of the Powerful Immunosuppressant (−)-Sanglifehrin A,"The potent immunosuppressive agent (-)-sanglifehrin A (5), initially discovered in a soil sample from Malawi, has been synthesized in a highly convergent and stereocontrolled manner. The enantioselective approach relies on initial construction of the iodovinyl carboxylic acid 14, which is coupled to tripeptide 59 in advance of a key macrolactonization step that generates 61a. An alternative protocol that involves the linkage of 14 to 46 for possible construction of the large ring failed due to an inability to bring about a corresponding macrolactamization maneuver. An efficient means for elaborating the C26-N42 spirolactam western sector of 5 is also detailed. This requisite fragment was assembled through the proper adaptation of consecutive aldol tactics for construction of the nine stereogenic centers, six of which are contiguous. The first aldol process consisted of the tin triflate-mediated reaction of the aldehyde derived from 72 with enantiopure ketone 73 to generate the syn C36-C37 relationship resident in 75. Once the conversion of 75 to 78 had been completed, the attachment to ketone 66 was effected with (+)-DIPCl, thereby setting the C33-C34 relationship as anti. Once functional group modifications had given rise to 62, spirolactamization was achieved to deliver predominantly 94, thereby setting the stage for the acquisition of vinyl stannane 13 and its subsequent palladium-catalyzed Stille coupling to 61b. Controlled acidic hydrolysis completed the synthesis of 5. Other important features of the present route are addressed where relevant.",10.1021/ja020091v,2002-03-27,0.6055413074419577
Journal of Organic Chemistry,"Synthesis of Pyrroles from 1-Dialkylamino-3-phosphoryl(or phosphanyl)allenes through 1,5-Cyclization of Conjugated Azomethine Ylide Intermediates","1-Dialkylamino-1,3-diaryl-3-diphenylphosphanylallenes 3a-e are thermally converted into a-annulated 3,5-diarylpyrroles 6a-f and [a]-annulated benzo[c]azepines 7a,b,d. These transformations are likely to include conjugated azomethine ylide intermediates that can undergo either a 1,5- or a 1,7-electrocyclization. The periselectivity is markedly shifted toward 1,5-cyclization when the diphenylphosphanyl substituent is replaced by the diphenylphosphoryl group. Thus, 1-dialkylamino-3-(diphenylphosphoryl)allenes 4a-f yield pyrroles 6 exclusively and with improved yields, unless the 3-aryl substituent in the allene is too electron-rich (e.g., benzodioxol-5-yl, 4f --> 7f). The preparation and thermal transformation of aminoallenes 4 over three or four steps can be conducted as a one-pot procedure, thus providing a convenient synthesis of [a]-annulated 3,5-diarylpyrroles from enaminoketones.",10.1021/jo049586o,2004-06-19,0.6055345315973734
Tetrahedron,"One-pot synthesis of nidorellaurenal and its one-step conversion to methyl nidorellaurinate, a constituent of",,10.1016/s0040-4039(00)78601-1,1980-01-01,0.6055319885906684
European Journal of Organic Chemistry,Enantioselective Synthesis of Jaspine B (Pachastrissamine) and Its C‐2 and/or C‐3 Epimers,"Abstract Jaspine B and its C‐2 and/or C3 epimers have been enantioselectively prepared from butadiene monoepoxide through a synthetic procedure consisting of allylic amination by palladium‐catalyzed dynamic kinetic asymmetric transformation, cross metathesis, and stereoselective dihydroxylation as key steps.",10.1002/ejoc.201001477,2011-01-26,0.6055263392512789
Tetrahedron,"A mild efficient iodine-catalyzed synthesis of novel anticoagulants with 2,8-dioxabicyclo[3.3.1]nonane core",,10.1016/j.tetlet.2013.02.092,2013-03-07,0.6055198185367532
Synthesis,"Facile, Stereocontrolled Synthetic Route towards Bis-functionalised Pyrrolizidines","A simple and convenient method for the synthesis of bis-functionalised pyrrolizidines starting from readily available N-Cbz-l-prolinal is described. This aldehyde was converted within two concise steps to the corresponding aminoepoxides, which were separately subjected to regioselective cyclisation induced by a reductive cleavage of the Cbz protecting group. The versatile and concise strategy holds great potential for practical application in the straightforward preparation of pyrrolizidine-based drugs and natural products.",10.1055/s-0037-1609582,2018-07-23,0.6055158010043146
Angewandte Chemie International Edition,Aldolase-Catalyzed Asymmetric Synthesis of Novel Pyranose Synthons as a New Entry to Heterocycles and Epothilones,Enzymatic reactions catalyzed by DERA provide the basis for a new strategy for the synthesis of novel pyranose synthons. The utility of this very convergent and effective method is demonstrated by the concise total synthesis of epothilones (see scheme; DERA=2-deoxyribose-5-phosphate aldolase).,10.1002/1521-3773(20020415)41:8<1404::aid-anie1404>3.0.co;2-g,2002-04-15,0.6055108914211387
Organic Letters,"Catalytic Asymmetric Total Synthesis of Naturally Occurring <i>Amaryllidaceae</i> Alkaloid, (+)-11-Hydroxyvittatine","The first catalytic asymmetric total synthesis of naturally occurring (+)-11-hydroxyvittatine ( 1a ) has been achieved in 9 steps and an overall yield of 14.4%. The enantioselectivity was achieved using an organocatalytic Corey–Itsuno reduction. Subsequent Mitsunobu reaction and a microwave-assisted intramolecular carbonyl-ene reaction enabled the construction of the core structure with three fixed stereocenters. Finally, a Pictet–Spengler cyclization completes the total synthesis of (+)-11-hydroxyvittatine ( 1a ). Our synthesis relies on simple and classical reactions to address the Amaryllidaceae alkaloids and will serve as an efficient route to access the other congeners.",10.1021/acs.orglett.5c02057,2025-06-17,0.60550852352489
Synlett,"Synthesis of the AB-Ring of 9,11-Secosterols","All articles of this category The first total synthesis of AB-ring system of an antiproliferative and cytotoxic 9,11-secosterol 1 is described. Enantiomerically pure (3 S ,5 S ,6 S ,10 S )-3,6-diacetoxy-10-methylbicyclo[4.4.0]decan-9-one 8 (steroidal numeration) was prepared from ( S )-Wieland-Miescher ketone. diastereoselectivity - hydroborations - bicyclic compounds - sterols - total synthesis",10.1055/s-2000-6562,2000-01-01,0.6055030275439082
Angewandte Chemie International Edition,Total Synthesis of Pyrolaside B: Phenol Trimerization through Sequenced Oxidative C−C and C−O Coupling,"A facile method to oxidatively trimerize phenols using a catalytic aerobic copper system is described. The mechanism of this transformation was probed, yielding insight that enabled cross-coupling trimerizations. With this method, the natural product pyrolaside B was synthesized for the first time. The key strategy used for this novel synthesis is the facile one-step construction of a spiroketal trimer intermediate, which can be selectively reduced to give the natural product framework without recourse to stepwise Ullmann- and Suzuki-type couplings. As a result, pyrolaside B can be obtained expeditiously in five steps and 16 % overall yield. Three other analogues were synthesized, thus highlighting the utility of the method, which provides new accessibility to this area of chemical space. A novel xanthene was also synthesized through controlled Lewis acid promoted rearrangement of a spiroketal trimer.",10.1002/anie.201915654,2020-02-05,0.6054845775910307
Synthesis,"A Stereoselective Anti-Aldol Route to (3R,3aS,6aR)-Hexahydrofuro[2,3-b]furan-3-ol: A Key Ligand for a New Generation of HIV Protease Inhibitors",-aldol reaction as the key step.,10.1055/s-2006-942547,2006-08-02,0.6054762208798293
Tetrahedron,Efficient synthesis of the gadolinium complex of a new C2-symmetric tetramine,,10.1016/s0040-4039(98)00375-x,1998-04-01,0.6054726022049521
Synthesis,Stereoselective Synthesis of C13–C28 Fragment of Marinomycin A,"Synthesis of the C13–C28 fragment of marinomycin A, consisting of all the five stereocenters, was achieved by asymmetric synthesis, starting from l -malic acid. The simple convergent approach utilized cross metathesis of two key olefinic fragments for the introduction of the C20–C21 double bond. Two of the five stereocenters, C19 and C27, were realized from l -malic acid, while, C17 and C23 are introduced by Sharpless asymmetric epoxidation and C25 by a selective allylation reaction.",10.1055/s-0034-1379697,2014-12-23,0.6054723708896435
Synthesis,"Selfcondensation of 4-Alkoxyacetophenone Anils: A New Route to 1,3,5-Tris[4-alkoxyphenyl]benzenes",Synthese par chauffage de phenylimines d'alcoxy-4 acetophenones avec le chlorhydrate d'aniline,10.1055/s-1984-30831,1984-01-01,0.6054709824845127
Synthesis,"A Facile Synthesis of Aryl Spirodioxines Based on a 3<i>H</i>,3′<i>H</i>-2,2′-Spirobi(benzo[<b><i>b</i></b>][1,4]dioxine) Skeleton","The synthesis of a series of 6,6-bisbenzannulated spiroketals containing a 3H,3′H-2,2′-spirobi(benzo[b][1,4]dioxine) ring system is reported. The key step involves addition of a monobenzyl-protected catechol to the epoxide unit of a glycidol bearing a benzyl-protected catechol. The resultant alcohol adduct is oxidized to a ketone that then undergoes hydrogenation and acid-catalyzed cyclization to produce the desired spirodioxines. © Georg Thieme Verlag Stuttgart.",10.1055/s-2007-966016,2007-04-26,0.6054668041755656
Tetrahedron,A domino ring-closing metathesis as a key-step in the synthesis of chiral lactones from d-mannitol,,10.1016/j.tetlet.2005.03.189,2005-04-14,0.6054591367457067
Organic Letters,"A New, Ring Closing Metathesis-Based Synthesis of (−)-Fumagillol","[reaction: see text]. A new strategy to access the fumagillin/fumagillol skeleton is proposed. An Evans aldolization and a RCM involving an enone are used for the preparation of a key cyclohexanone intermediate, which was readily converted to fumagillol. The synthesis also features an efficient preparation of isogeraniol and isogeranic acid.",10.1021/ol016343z,2001-07-31,0.6054521977844209
Tetrahedron,"Asymmetric synthesis IV. Preparation of chiral α-aminonitriles from a new N-cyanomethyl-1,3-oxazolidine synthon",,10.1016/s0040-4039(00)89192-3,1985-01-01,0.6054502818290826
Journal of Organic Chemistry,"Enantioselective Synthesis of 12-<i>epi</i>-PGF<sub>2</sub><sub>α</sub> and 12,15-<i>diepi</i>-PGF<sub>2</sub><sub>α</sub>","An enantioselective synthesis of 12- epi -PGF 2 α ( 3 ) and 12,15- diepi -PGF 2 α ( 4 ), PG-like compounds that are probably generated in vivo by nonenzymatic, free-radical-induced peroxidation of arachidonic acid, has been achieved starting from the commercially available Corey lactone ( 9 ). The key strategy involves SmI 2 reduction of the γ,δ-epoxy-α,β-unsaturated ester 7, followed by in situ trapping with hexanal; subsequent hydrogenation and decarboxylation affords the stereoselective construction of the lower side chain. This new method is expected to provide a convenient access to various PG-like isoprostanes derived from oxidation of arachidonic acid and cis -4,7,10,13,16,19-docosahexaenoic acid.",10.1021/jo990906r,1999-08-25,0.6054473331693162
Journal of Organic Chemistry,"Structure Reassignment and Synthesis of Jenamidines A<sub>1</sub>/A<sub>2</sub>, Synthesis of (+)-NP25302, and Formal Synthesis of SB-311009 Analogues","The proposed structures of jenamidines A, B, and C (1-3) were revised to jenamidines A1/A2, B1/B2, and C (8-10). Jenamidines A1/A2 (8) were synthesized from activated proline derivative 43 by conversion to 26 in two steps and 50% overall yield. Acylation of 26 with acid chloride 38d gave 39d, which was deprotected with TFA and then mild base to give 8 in 45% yield from 26. (-)-trans-2,5-Dimethylproline ethyl ester (49) was prepared by the enantioselective Michael reaction of ethyl 2-nitropropionate (51) and methyl vinyl ketone (50) using modified dihydroquinine 60 as the catalyst. Further elaboration converted 49 to natural (+)-NP25302 (12). A Wittig reaction of proline NCA (76) with ylide 79 gave 72 as a 9/1 E/Z mixture in 27% yield, completing a one-step formal synthesis of SB-311009 analogues.",10.1021/jo061650+,2006-09-29,0.6054422324846791
Journal of Organic Chemistry,"Synthesis, Resolution, and Absolute Stereochemistry of (−)-Blestriarene C","A naturally occurring 1,1'-biphenanthrene, blestriarene C (1), was prepared in 13 steps and 30% overall yield. The key steps are the ester-mediated nucleophilic aromatic substitution on 2,6-di-tert-butyl-4-methoxyphenyl 5-isopropoxy-2-methoxybenzoate (4) by 2-methoxy-4-methoxymethoxy-6-methylphenylmagnesium bromide (5) and a novel intramolecular cyclization of the resulting 4-isopropoxy-2'-methoxy-4'-methoxymethoxy-6'-methylbiphenyl-2-carboxylic ester 14 to 7-isopropoxy-4-methoxy-2-(methoxymethoxy)phenanthren-9-ol (15). The racemic blestriarene C was optically resolved by chiral HPLC on a preparative scale to give several 10-mg yields of both the enantiomers in up to 95% ee. The absolute stereochemistry was determined to be S(a)-(-) by the axial chirality recognition method, which was based on the stereospecific formation of a 12-membered cyclic diester containing two biaryl-o,o'-diyl unites joined by ester -CO(2)- linkages. The validity of the method was confirmed by an X-ray crystallographic analysis and ab initio conformational analyses of such 12-membered cyclic diesters. It was found that blestriarene C and its 7,7'-diisopropyl ether 2 underwent rapid photoracemization even under ambient light exposure.",10.1021/jo026747k,2003-02-07,0.6054421324643281
Organic Letters,Total Synthesis of the Novel NF-κB Inhibitor (−)-Cycloepoxydon,"An enantioselective total synthesis of the novel, biologically active epoxyquinone natural product (-)-cycloepoxydon has been accomplished from the readily available Diels-Alder adduct of cyclopentadiene and p-benzoquinone. A new cycloepoxydon related heptacyclic dimer has been prepared and characterized. [reaction: see text]",10.1021/ol036521j,2004-02-05,0.6054379637252623
Journal of Organic Chemistry,Intramolecular Arylation of Tertiary Enamides through Pd(OAc)<sub>2</sub>-Catalyzed Dehydrogenative Cross-Coupling Reaction: Construction of Fused <i>N</i>-Heterocyclic Scaffolds and Synthesis of Isoindolobenzazepine Alkaloids,"-catalyzed intramolecular dehydrogenative cross-coupling reaction between tertiary enamides, which were derived from the condensation of 2-arylethylamines and methyl o-acetylbenzoate, and arenes enabled synthesis of 7,8-dihydro-5 H-benzo[4,5]azepino[2,1- a]isoindol-5-one derivatives under mild conditions. The synthetic method was applied in the total synthesis of aporhoeadane alkaloids palmanine, lennoxamine, and chilenamine in only three or four steps.",10.1021/acs.joc.9b00010,2019-02-08,0.6054376783224219
Tetrahedron,Cyclopentannulation on 3-phospholenes: an expedient route to the 2-phosphabicyclo[3.3.0]octene ring system,,10.1016/s0040-4039(03)01296-6,2003-06-30,0.605432558842612
Tetrahedron,Novel photoreorganisation of 4-oxo-4-1-benzopyrans: Synthesis of pyranobenzopyrones,,10.1016/s0040-4039(00)96042-8,1987-01-01,0.605426521246602
Tetrahedron,"A novel synthesis of 2,3-dinor-6-oxo-prostaglandin F1α",,10.1016/s0040-4039(01)80209-4,1984-01-01,0.605426521246602
Organic Process Research & Development,An Efficient Commercial Process for the Preparation of Isotretinoin,"We describe an efficient process for the preparation of isotretinoin (13-cis isomer of vitamin A acid) in a single step starting from β-ionylidene acetaldehyde ( 5 ). The process conditions are convenient to operate on a commercial scale and afford isotretinoin of excellent quality; levels of related isomeric impurities such as tretinoin (all trans retinoic acid) and 9,13-di- cis -retinoic acid are extremely low. Thus, condensation of dienolate of methyl 3,3-dimethylacrylate with β-ionylidene acetaldehyde ( 5 ) followed by aqueous acidic workup afforded isotretinoin in >95% purity. The condensation reaction proceeds via in situ formation of lactone ( 8 ); furthermore, the reaction conditions have been optimized to exploit in situ generated methoxide anion for lactone ring opening to afford the desired product. Distinct advantages of this process are that it does not require isolation of intermediate lactone and utilizes in situ generated methoxide for lactone ring opening, thus obviating the need for an additional step and base. We also describe an optimized process for the preparation of β-ionylidene acetaldehyde ( 5 ), a key intermediate for isotretinoin.",10.1021/op0497815,2005-03-03,0.6054236472562762
Journal of Organic Chemistry,Total Synthesis of Miuraenamides A and D,"Miuraenamides A and D, cyclodepsipeptides with antimicrobial and antitumor activity, were synthesized. The synthesis of an unsaturated hydroxycarboxylic acid moiety, starting from a chiral epoxide, was achieved by Suzuki-Miyaura coupling as a key step. As a result, the overall yield for miuraenamide A over the longest linear sequence is 3.2%, while the yield of the previously reported procedure is 1.9%. In addition, the cell growth-inhibitory activity and anti-Phytophthora activity of the synthesized compounds were evaluated.",10.1021/acs.joc.6b02061,2016-09-23,0.6054194525277213
Synlett,"Studies in Spiroketal Synthesis 2. A Tandem Cyclization Route to the 1,7-Dioxaspiro[5.5]undecane Ring System","All articles of this category A novel route to the 1,7-dioxaspiro[5.5]undecane ring system has been demonstrated using a double carbonyl tandem cyclization strategy. The reaction begins with intramolecular β-cleavage of a β-lactone ring by a ketone oxygen, and terminates with nucleophilic addition to a spirooxocarbenium ion. spiroketals - β-lactones - oxocarbenium ions - silane nucleophiles",10.1055/s-1996-5688,2000-12-31,0.6054174120731728
Organic Process Research & Development,Practical Synthesis of MDM2 Antagonist RG7388. Part 1: A Cu(II)-Catalyzed Asymmetric [3 + 2] Cycloaddition,"An efficient asymmetric synthesis of MDM2 antagonist RG7388 is reported. The highly functionalized chiral pyrrolidine carboxamide was assembled via a Cu(OAc) 2 /( R )-BINAP catalyzed asymmetric [3 + 2] cycloaddition, which gave the exo and endo adducts in a ratio of 10:1, with high enantiomeric excess for the exo isomer. A one-pot hydrolysis and retro-Mannich/Mannich isomerization of the cycloaddition adducts in the presence of aqueous sodium hydroxide afforded RG7388 in high chemical and enantiomeric purities and 69% overall yield.",10.1021/acs.oprd.6b00320,2016-10-31,0.6054116164145634
Journal of the American Chemical Society,C–H Functionalization-Enabled 11-Step Semisynthesis of (−)-Veragranine A and Characterization of Synthetic Analogs in Osteoarthritis-related Pain Treatment,"High Resolution Image Download MS PowerPoint Slide We report an efficient semisynthesis of the cholestane steroidal alkaloid (−)-veragranine A with a 6/6/6/5/6/6 hexacyclic ring system, eight stereocenters, and a unique C12–C23 linkage. Our synthesis features a Schönecker–Baran C–H oxidation at C12, a Suzuki–Miyaura cross-coupling to form the C12–C23 bond, and a hydrogen atom transfer (HAT)-initiated Minisci C–H cyclization to forge the C20–C22 bond with desired stereochemistry at C20. These enabling transformations significantly enhanced the overall synthetic efficiency and delivered (−)-veragranine A in 11 steps and over 200 mg from cheap and readily available dehydroepiandrosterone. In addition, this approach allowed flexible syntheses of novel synthetic analogs for biological evaluations in sensory neurons in vitro and in an in vivo model of arthritic pain, from which two novel lead compounds were identified for further development.",10.1021/jacs.4c04025,2024-06-06,0.6054004954900416
Organic Letters,"Synthesis of Substituted Piperidines, Indolizidines, Quinolizidines, and Pyrrolizidines via a Cycloaddition Strategy Using Acetylenic Sulfones as Alkene Dipole Equivalents","The conjugate additions of β- and γ-chloroamines to acetylenic sulfones afford enamine sulfones, which then undergo intramolecular alkylation to produce the corresponding cyclic enamines. This provides a convenient route to substituted piperidines, indolizidines, quinolizidines, and pyrrolizidines. The enantioselective total synthesis of the alkaloid (−)-indolizidine 167B (also named gephyrotoxin 167B ) was thus achieved by the cycloaddition of ( S )-2-(2-chloroethyl)pyrrolidine to 1-( p -toluenesulfonyl)-1-pentyne, followed by stereoselective reduction of the enamine moiety and reductive desulfonylation.",10.1021/ol990592u,1999-05-27,0.6053959165658483
Synlett,Eight-Step Total Synthesis of the Cyclopeptide Alkaloid Mucronine E,All articles of this category (opens in new window),10.1055/s-2007-1000833,2007-12-19,0.6053829828843178
Journal of Organic Chemistry,"New Stereoselective Route to the Epoxyquinol Core of Manumycin-Type Natural Products. Synthesis of Enantiopure (+)-Bromoxone, (−)-LL-C10037α, and (+)-KT 8110","A practical route is decribed for the preparation of the C(7)N core of manumycin-type compounds. Starting from p-benzoquinone, optically pure compounds in both forms can be prepared via enzymatic resolution of a derived diacetoxy conduritol. A diepoxy aminoinositol is accessible which can function for formation of enantiopure epoxyquinones and quinols. Examples are given for acylation reactions of this amine with several acyl derivatives. With this approach (-)-LL-C10037alpha and quinones such as (+)-KT-8110 with 5R,6S-configuration can be synthesized through oxidation. In addition a short route to (+)-bromoxone is described. Most steps include simple epoxide formation and cleavage reactions which all can be carried out in a high stereoselective manner.",10.1021/jo991324c,2000-01-14,0.6053823075981413
Angewandte Chemie International Edition,A Concise and Highly Enantioselective Total Synthesis of (+)‐<i>anti</i>‐ and (−)‐<i>syn</i>‐Mefloquine Hydrochloride: Definitive Absolute Stereochemical Assignment of the Mefloquines,"A concise asymmetric (>99:1 e.r.) total synthesis of (+)-anti- and (-)-syn-mefloquine hydrochloride from a common intermediate is described. The key asymmetric transformation is a Sharpless dihydroxylation of an olefin that is accessed in three steps from commercially available materials. The Sharpless-derived diol is converted into either a trans or cis epoxide, and these are subsequently converted into (+)-anti- and (-)-syn-mefloquine, respectively. The synthetic (+)-anti- and (-)-syn-mefloquine samples were derivatized with (S)-(+)-mandelic acid tert-butyldimethylsilyl ether, and a crystal structure of each derivative was obtained. These are the first X-ray structures for mefloquine derivatives that were obtained by coupling to a known chiral, nonracemic compound, and provide definitive confirmation of the absolute stereochemistry of (+)-anti- as well as (-)-syn-mefloquine.",10.1002/anie.201507304,2015-09-30,0.605373615848422
Journal of Organic Chemistry,Synthesis of Benzo-fused Heterocycles by Intramolecular α-Arylation of Ketone Enolate Anions,"A two-step synthesis of six-, seven-, eight-, and nine-member benzo-fused heterocycles in good to excellent yields is reported. The synthetic strategy involves the generation of a new intramolecular α-aryl ketone bond by the photostimulated S(RN)1 reaction of ketone enolate anions linked to a pendant haloarene as the key step. On the other hand, an intramolecular C(Ar)-C(Ar) coupling led to the formation of five- and six-member benzo-fused heterocycles (9H-carbazole and phenanthridine) when an aromatic amide anion is competitively formed.",10.1021/jo202012n,2011-12-05,0.6053587268442285
Journal of the American Chemical Society,Catalytic <i>Z</i>-Selective Cross-Metathesis in Complex Molecule Synthesis: A Convergent Stereoselective Route to Disorazole C<sub>1</sub>,"A convergent diastereo- and enantioselective total synthesis of anticancer and antifungal macrocyclic natural product disorazole C1 is reported. The central feature of the successful route is the application of catalytic Z-selective cross-metathesis (CM). Specifically, we illustrate that catalyst-controlled stereoselective CM can be performed to afford structurally complex Z-alkenyl-B(pin) as well as Z-alkenyl iodide compounds reliably, efficiently, and with high selectivity (pin = pinacolato). The resulting intermediates are then joined in a single-step operation through catalytic inter- and intramolecular cross-coupling to furnish the desired 30-membered ring macrocycle containing the critical (Z,Z,E)-triene moieties.",10.1021/ja509973r,2014-11-07,0.6053525550849552
Synthesis,Efficient Synthesis of Novel Jolkinolides and Related Derivatives Starting from Stevioside,"Jolkinolides are naturally occurring tetracyclic diterpene from Euphorbia genus, which exhibit promising antitumor and other biological activity. Efficient syntheses of the 19-carboxy derivative of jolkinolide A and 19-hydroxyjolkinolide E have been accomplished in 13 steps with a total yield of 7.8% starting from the easily available and low-cost sweetener stevioside, and some related derivatives have also been synthesized.",10.1055/s-0031-1289293,2011-10-20,0.6053430476362773
Organic Letters,A Versatile Enantioselective Synthesis of Barrenazines,"A versatile enantioselective total synthesis of barrenazines A and B has been accomplished from 1,4-butanediol. The key steps of the synthesis are a sequential allylboration/ring-closing metathesis for the construction of the tetrahydropyridine ring and the preparation of a functionalized 4-azidopiperidin-5-one through a stereoselective epoxidation and regioselective ring-opening reaction. The C(2)-symmetrical pyrazine skeleton of barrenazines was prepared by dimerization of the azidopiperidinone, and the carbon side chain was completed by copper-catalyzed reactions using Grignard reagents.",10.1021/ol902920u,2010-01-21,0.605329404205081
Synlett,"Synthesis of N-{5-Oxo-2-thioxo(2,5-dithioxo)hexahydroimidazo-[4,5-d]imidazol-1(2H)-yl}formamides","A synthetic route to novel N -{5-oxo-2-thioxo(2,5-dithioxo)hexahydroimidazo[4,5- d ]imidazol-1(2 H )-yl}formamides, by a tandem N-formylation and ring-contraction reaction of 5,7-disubstituted 3-thioxoperhydroimidazo[4,5- e ]-1,2,4-triazine-6-ones(thiones) with formic acid, has been developed.",10.1055/s-0036-1588388,2017-01-10,0.6053232475482095
Organic Letters,Enantioselective Total Synthesis of Macrolide Antitumor Agent (−)-Lasonolide A,"[structure: see text] An enantioselective total synthesis of (-)-lasonolide A is described. The upper tetrahydropyran ring was constructed stereoselectively by an intramolecular 1,3-dipolar cycloaddition reaction. The bicyclic isooxazoline led to the tetrahydropyran ring as well as the quaternary stereocenter present in the molecule. The lower tetrahydropyran ring was assembled by a catalytic asymmetric hetero-Diels-Alder reaction as the key step. Three stereocenters were enantioselectively installed in this single step reaction.",10.1021/ol0701013,2007-03-17,0.6053230823424144
Journal of Organic Chemistry,Synthesis of Novel KDR Kinase Inhibitors through Catalytic Reductive Cyclization of <i>o</i>-Nitrobenzylcarbonyl Compounds,An efficient synthesis of o-nitrobenzylcarbonyl compounds is demonstrated through the Swern-type oxidation of readily accessible phenethanol analogues. Reductive cyclization of o-nitrobenzylcarbonyl 3 using catalytic Raney nickel gives 1H-indol-2-yl-1H-quinoline 2 in 95% yield. Hydrolysis of 2 affords the KDR kinase inhibitor 1 in quantitative yield. The examination of the reductive cyclization reaction and optimization of conditions is described.,10.1021/jo048843m,2004-10-01,0.6053178387856663
Organic Letters,<i>tert</i>-Butyl Hydroperoxide Mediated Cascade Synthesis of 3-Arylsulfonylquinolines,3-Arylsulfonylquinoline derivatives play important roles as pharmaceutical drugs. A new method for the synthesis of 3-arylsulfonylquinoline derivatives has been achieved through tert-butyl hydroperoxide mediated cycloaddition between N-propargyl aromatic amine derivatives and arylsulfonylhydrazides without the addition of any metals. This transformation offers a straightforward route to the formation of a C-S bond and quinoline ring in one step via a sulfonylation-cyclization-aromatization process.,10.1021/acs.orglett.6b00198,2016-03-09,0.605309045164114
Tetrahedron,"Synthetic applications of 2-(1,3-Dithian-2-yl)indoles V.1 asymmetric synthesis of dasycarpidone-type indole alkaloids",,10.1016/0040-4039(95)00047-g,1995-03-01,0.6053061035231311
Journal of Organic Chemistry,"Access to 12-Membered Cyclic <i>ortho</i>,<i>meta</i>-Diarylheptanoids: Total Synthesis of Actinidione via Isomyricanone","-diarylheptanoids. The key features of the synthesis include both a Suzuki-Miyaura coupling and a ring closing metathesis. Actinidione, a promising natural product, along with a bioactive tetracyclic derivative were obtained in 14 steps for the first time from cheap commercially available substrates with an overall yield of 18-21%. Our modus operandi complies with the principles of the synthesis ideality by using notably strategic reactions.",10.1021/acs.joc.0c02489,2021-01-21,0.6053043657060504
Journal of Organic Chemistry,Total Synthesis of (+)–Haperforin G,(+)-Haperforin G was synthesized in 20 steps from commercially available starting materials. A Co-catalyzed intramolecular Pauson–Khand reaction was used for stereoselective construction of cyclopentanone bearing an all-carbon quaternary stereogenic center at the bridge-head position. Light-initiated photocatalysis was used for convergent and asymmetric cross-coupling of the unstabilized C(sp 3 ) radical with an enone. The developed chemistry paves the way to the synthesis of structurally diverse analogs of haperforin G ( 6 ).,10.1021/acs.joc.3c00542,2023-07-17,0.6052907307549908
Tetrahedron,Amino acid catalyzed direct enantioselective formation of carbohydrates: one-step de novo synthesis of ketoses,,10.1016/j.tetlet.2005.03.084,2005-04-02,0.6052881941509894
Journal of Organic Chemistry,A Stereocontrolled Synthesis of a Phosphorothioate Cyclic Dinucleotide-Based STING Agonist,"We describe a stereodefined synthesis of the newly identified non-natural phosphorothioate cyclic dinucleotide (CDN) STING agonist, BMT-390025. The new route avoids the low-yielding racemic approach using P(III)-based reagents, and the stereospecific assembly of the phosphorothioate linkages are forged via the recently invented P(V)-based platform of the so-called PSI (Ψ) reagent system. This P(V) approach allows for the complete control of chirality of the P-based linkages and enabled conclusive evidence of the absolute configuration. The new approach offers robust procedures for preparing the stereodefined CDN in eight steps starting from advanced nucelosides, with late-stage direct drop isolations and telescoped steps enabling an efficient scale-up that proceeded in an overall 15% yield to produce multigram amounts of the CDN.",10.1021/acs.joc.1c00784,2021-06-14,0.6052874741451975
Tetrahedron,"A new protecting group ‘3′,5′-O-sulfinyl’ for xylo-nucleosides. A simple and efficient synthesis of 3′-amino-3′-deoxyadenosine (a puromycin intermediate), 2,2′-anhydro-pyrimidine nucleosides and 2′,3′-anhydro-adenosine",,10.1016/j.tetlet.2003.10.092,2003-12-02,0.6052868542662521
Organic Letters,Structural Revision of (+)-Uprolide F Diacetate Confirmed by Asymmetric Total Synthesis,"A new structure for the cytotoxic cembranolide uprolide F diacetate (UFD) was proposed, and an enantioselective total synthesis was accomplished to confirm that our revised structure correctly represented the natural UFD and its absolute configuration. Our synthesis features a late-stage, highly efficient, and diastereoselective Nozaki-Hiyama-Kishi macrocyclization (95% yield) and an unexpected reagent-controlled reversible translactonization, which, being the first example within the cembranolide family, might have biogenetic implications and be of great importance to synthetic studies of the α-methylene-γ-lactone-bearing cembranolides.",10.1021/acs.orglett.5b00700,2015-04-01,0.6052794928026387
Angewandte Chemie International Edition,Organocatalytic Atroposelective Synthesis of N−N Axially Chiral Indoles and Pyrroles by De Novo Ring Formation,"The first highly atroposelective construction of N-N axially chiral indole scaffolds was established via a new strategy of de novo ring formation. This strategy makes use of the organocatalytic asymmetric Paal-Knorr reaction of well-designed N-aminoindoles with 1,4-diketones, thus affording N-pyrrolylindoles in high yields and with excellent atroposelectivities (up to 98 % yield, 96 % ee). In addition, this strategy is applicable for the atroposelective synthesis of N-N axially chiral bispyrroles (up to 98 % yield, 97 % ee). More importantly, such N-N axially chiral heterocycles can be converted into chiral organocatalysts with applications in asymmetric catalysis, and some molecules display potent anticancer activity. This work not only provides a new strategy for the atroposelective synthesis of N-N axially chiral molecules but also offers new members of the N-N atropisomer family with promising applications in synthetic and medicinal chemistry.",10.1002/anie.202116829,2022-01-26,0.6052759709024765
Journal of Organic Chemistry,Total Synthesis of Cryptophycin-24 (Arenastatin A) Amenable to Structural Modifications in the C16 Side Chain,"Two efficient protocols for the synthesis of tert-butyl (5S,6R,2E, 7E)-5-[(tert-butyldimethylsilyl)oxy]-6-methyl-8-phenyl-2, 7-octadienoate, a major component of the cryptophycins, are reported. The first utilized the Noyori reduction and Frater alkylation of methyl 5-benzyloxy-3-oxopentanoate to set two stereogenic centers, which became the C16 hydroxyl and C1' methyl of the cryptophycins. The second approach started from 3-p-methoxybenzyloxypropanal and a crotyl borane reagent derived from (-)-alpha-pinene to set both stereocenters in a single step and provided the dephenyl analogue, tert-butyl (5S,6R,2E)-5-[(tert-butyldimethylsilyl)oxy]-6-methyl-2, 7-octadienoate, in five steps. This compound was readily converted to the 8-phenyl compound via Heck coupling. The silanyloxy esters were efficiently deprotected and coupled to the C2-C10 amino acid fragment to provide desepoxyarenastatin A and its dephenyl analogue. The terminal olefin of the latter was further elaborated via Heck coupling. Epoxidation provided cryptophycin-24 (arenastatin A).",10.1021/jo000767+,2000-10-14,0.6052735349683739
Organic Letters,Total Synthesis of Stephanotic Acid Methyl Ester,"[structure: see text]The methyl ester of the naturally occurring macrocyclic pentapeptide stephanotic acid, containing an unusual beta-substituted alpha-amino acid with a tryptophan C-6 to leucine beta-carbon link, has been synthesized. The key steps include the formation of this amino acid through a thioxo-oxazolidine intermediate and a Horner-Wadsworth-Emmons reaction using a phosphonoglycine, derived by a dirhodium(II)-catalyzed N-H insertion reaction, to give a dehydroamino acid and subsequent rhodium(I)-catalyzed asymmetric hydrogenation to introduce the modified tryptophan residue.",10.1021/ol060153c,2006-04-21,0.6052730491182129
Synthesis,A New Route to 2-Bromo-1-alkenes by Hydrobromination of 1-Alkynes with Tetraethylammonium Hydrogen Dibromide,,10.1055/s-1980-29212,1980-01-01,0.6052720829185894
Organic Letters,Total Synthesis of (−)-Preussochromone D,"An efficient, stereoselective synthesis of the natural product (-)-preussochromone D is reported. The tricyclic skeleton was assembled by a diastereoselective intramolecular aldol addition of a chromanone to an α-ketoester. Further key steps are an asymmetric 1,4-addition of diisopropenyl zinc to a chromenone and an intermolecular diastereoselective aldol addition of methyl diazoacetate to an aldehyde. The diazo group was oxidized to generate the α-ketoester while oxidative side reactions at the chromanone could be prevented by the use of a difluoromethyl ether as a protecting group.",10.1021/acs.orglett.9b01594,2019-05-28,0.6052677744237205
Organic Letters,Scalable Synthesis of the Amber Odorant 9-<i>epi</i>-Ambrox through a Biomimetic Cationic Cyclization/Nucleophilic Bromination Reaction,"A novel biomimetic nucleophilic bromocyclization reaction is used in the key step of a new and straightforward synthesis of 9-epi-Ambrox, an organic compound of high interest and value in the context of fragrances. This strategic reaction allows access to 9-epi-Ambrox on a gram scale from a dienyne derivative, easily available from geraniol, following a sequence of seven steps (35% global yield) with just one purification process. Both enantiomers of the molecule were obtained by a challenging enzymatic resolution.",10.1021/acs.orglett.6b02266,2016-09-02,0.6052639369940178
European Journal of Organic Chemistry,A Substituent‐Directed Strategy for the Selective Synthesis of L‐Hexoses: An Expeditious Route to L‐Idose,"Abstract L‐Hexoses are rare but biologically significant components of various important biomolecules. However, most are prohibitively expensive (if commercially available) which limits their study and biotechnological exploitation. New, efficient methods to access L‐hexoses and their derivatives are thus of great interest. In a previous study, we showcased a stereoselective Bu 3 SnH‐mediated transformation of a 5‐ C ‐bromo‐D‐glucuronide to an L‐iduronide. We have now drawn inspiration from this result to derive a new methodology – one that can be harnessed to access other L‐hexoses. DFT calculations demonstrate that a combination of a β‐F at the anomeric position and a methoxycarbonyl substituent at C‐6 is key to optimising the selectivity for the L‐hexose product. Our investigations have also culminated in the development of the shortest known synthetic route to a derivative of L‐idose from a commercially available starting material (45 % yield over 3 steps). Collectively, these results address the profound lack of understanding of how to synthesise L‐hexoses in a stereoselective fashion.",10.1002/ejoc.202100042,2021-02-04,0.6052551005599806
Tetrahedron,A short and efficient asymmetric synthesis of komaroviquinone,,10.1016/j.tetlet.2010.09.110,2010-10-04,0.60522593453205
Organic Letters,Synthesis of PPAR Agonist via Asymmetric Hydrogenation of a Cinnamic Acid Derivative and Stereospecific Displacement of (<i>S</i>)-2-Chloropropionic Acid,"The synthesis of the peroxime proliferator activated receptor (PPAR) alpha,gamma-agonist (1) was accomplished with high enantio- and diastereoselectivity by employing an asymmetric hydrogenation strategy, of an alpha-alkoxy cinnamic acid derivative, to set the C-2 chiral center. A diastereospecific S(N)2 displacement under mild basic conditions established the C-10 stereochemistry without any detectable racemization of the two epimerizable chiral centers.",10.1021/ol050367e,2005-04-15,0.6052215197299396
Tetrahedron,A new synthesis of 5-hydroxy-6-methyluracil,,10.1016/j.tetlet.2012.08.133,2012-09-05,0.6052197856734236
Organic Letters,Dithiane Induced Cycloaddition/Aromatization Tactic for the Synthesis of Multisubstituted Furans,"The development of a new transition-metal-free tactic for convergent, one-pot synthesis of multisubstituted furans by β-chloro-vinyl dithiane cyclization with aldehydes is described. Key to the success was the development of a new vinylidene dithiane site as a donor allene that generates the active dihydrofuran, which undergoes in situ aromatization under mild conditions.",10.1021/acs.orglett.6b00699,2016-04-18,0.6052078748170857
Journal of the American Chemical Society,Enantioselective Synthesis of (−)-Maoecrystal V by Enantiodetermining C–H Functionalization,"The evolution of a program directed at the enantioselective total synthesis of maoecrystal V, a highly modified ent-kauranoid, is described. An early stage chiral auxiliary-directed asymmetric C-H functionalization for the construction of a key benzofuran intermediate enabled the first asymmetric synthesis of the natural enantiomer of maoecrystal V, confirming the assigned stereochemistry. A divergent course of the central intramolecular Diels-Alder reaction, which is dependent on the nature of the dienophile, initially led to the development of an unanticipated and previously unknown isomer of maoecrystal V, which we named maoecrystal ZG. In light of the reported selective and potent cytotoxic activity of maoecrystal V, the cytotoxic properties of maoecrystal ZG were also investigated.",10.1021/ja510573v,2014-11-20,0.6052052971805153
Angewandte Chemie International Edition,A Biomimetic Synthesis of a Porphobilinogen Precursor Using a Mukaiyama Aldol Reaction,Four steps suffice! A protected porphobilinogen was obtained in 25 % yield in a straightforward synthesis starting from a derivative of 5-aminolevulinate. The key was the use of a cyanide derivative instead of the azide. The synthesis imitates the mechanism proposed by Shemin for the biosynthesis of porphobilinogen. Phth = phthaloyl.,10.1002/(sici)1521-3773(19980216)37:3<358::aid-anie358>3.0.co;2-y,1998-02-16,0.6052046762877167
Tetrahedron,"Novel route to b-fused thiazoles starting from a 2-chloro-1-phenacylpyridinium salt and KSCN. Crystal structures of thiazolo- and oxazolo[3,2-a]pyridinium thiocyanates",,10.1016/s0040-4039(99)01601-9,1999-10-01,0.605201024905653
Synlett,"Enantioselective Synthesis of (3S,4S)-4-Methyl-3-heptanol, a Beetle Pheromone, via the Regioselective Cleavage of an α-Epoxy Oxazolidine","All articles of this category Chiral α-epoxy oxazolidines derived from ( R )-phenyl glycinol were reacted with organo cuprates in a totally regio and stereoselective way. This key-step sustained the synthesis of enantiopure (3 S ,4 S )-4-methyl-3-heptanol, a beetle aggregation pheromone, and of its (3 S ,4 R ) anti stereisomer, the enantiomer of an ant trail pheromone. oxazolidine - organo cuprates - pheromones - torsional strain - dipolar repulsion",10.1055/s-1996-5478,1996-06-01,0.6051883458380413
Journal of Organic Chemistry,Formal Total Synthesis of Hemibrevetoxin B by an Oxiranyl Anion Strategy,"The synthesis of the tetracyclic structure of hemibrevetoxin B (1) was achieved through a linear approach involving sequential coupling of three kinds of sulfonyl-stabilized oxiranyl anions, 5b, 6b, and 7b, to the monocyclic tetrahydropyran 4 containing the requisite substituents. Two iterations of alkylation of an oxiranyl anion and 6-endo cyclization provided the 6,6,6-tricyclic ring system 34, which was efficiently transformed into the 6,6,7-ring system 35 by ring expansion using trimethylsilyldiazomethane. Installation of the final oxepane ring into 38 was carried out using a combination of the oxiranyl anion methodology and ring enlargement just described. Stereoselective introduction of a tertiary methyl group into 41 provided the tetracyclic compound 42a, which contains all the asymmetric centers of 1. Elaboration of 42a to the known compound 2, which was already transformed into hemibrevetoxin B, completed the formal total synthesis of the natural product.",10.1021/jo980320p,1998-08-08,0.6051829323159128
Organic Letters,Synthetic Route to the GE3 Cyclodepsipeptide,[reaction: see text] A reasonably efficient [2 + 2 + 2] fragment condensation strategy has been developed for assembling the cyclodepsipeptide sector of GE3 that involves 5-7. A Carpino HATU-mediated macrolactamization was used to close the 19-membered cyclodepsipeptide ring.,10.1021/ol025895u,2002-05-01,0.6051825485355964
Synlett,Total Synthesis of Camptothecins: An Update,"Over the last few decades, considerable research efforts have been directed toward the development of effective chemical syntheses of camptothecin and its analogs. The last comprehensive review of this area was published in 2003 and many effective new methods have since been reported for the stereoselective synthesis of the camptothecin alkaloids. In this account, we have summarized most of the novel synthetic approaches developed for the synthesis of camptothecins during the last decade. We have focused on strategies for the construction of the pentacyclic ring system and the different methods used to install the chiral quaternary center on the E ring of camptothecin. 1 Introduction 2 Synthesis of Racemic Camptothecins 3 Enantioselective Synthesis of Camptothecins 3.1 Sharpless Asymmetric Dihydroxylation 3.2 Catalytic Asymmetric Cyanosilylation 3.3 Auxiliary-Induced Asymmetric Carbonyl Addition 3.4 Catalytic Asymmetric Ethylation 3.5 Asymmetric Hydroxylation 4 Conclusion",10.1055/s-0036-1588738,2017-03-15,0.6051665957793646
Tetrahedron,Enantioselective synthesis of nagilactone F via vinylsilane-terminated cationic cyclization,,10.1016/s0040-4039(00)76743-8,1994-03-01,0.6051606386469285
Tetrahedron,"Highly stereoselective addition of Grignard reagents to C-cyclopropylnitrone via the bisected s-trans conformation. An efficient synthesis of PEDC, a potent NMDA receptor antagonist having a cyclopropane structure",,10.1016/s0040-4039(00)00823-6,2000-07-01,0.6051444567427957
Journal of Organic Chemistry,"Synthesis and Characterization of Highly Conjugated, Chiral Bridging Ligands","This paper describes the synthesis of four chiral derivatives of the electronically highly conjugated tetra-2-pyridylpyrazine (TPPZ) bridging ligand, which are denoted (R)- and (S)-4,5- and 5,6-pineno-tetra-2-pyridylpyrazine (PTPPZ). Preparation of these ligands was undertaken through the use of commercially available, enantiomerically pure (1R)- and (1S)-alpha-pinene, which was functionalized and subsequently employed in a Krohnke pyridine synthesis involving a furan-substituted pyridinium salt to yield a chiral, furan-substituted pyridyl intermediate. Oxidative degradation and subsequent reduction of this furan led to a chiral, substituted 2-pyridylaldehyde, which underwent a pyridoin condensation followed by cyclization to produce the final PTPPZ ligands.",10.1021/jo048515m,2004-11-16,0.6051418865078907
Journal of the American Chemical Society,A Unified Total Synthesis of the Immunomodulators (−)-Rapamycin and (−)-27-Demethoxyrapamycin:  Construction of the C(21−42) Perimeters,"A total synthesis of the potent, naturally occurring immunomodulators (−)-rapamycin ( 1 ) and (−)-27-demethoxyrapamycin ( 2 ) has been achieved via a unified, highly convergent synthetic strategy. Both targets were elaborated from common building blocks A−E, the latter available in decagram quantities. Herein we present the construction of the ABC northern perimeters of 1 and 2 . The accompanying paper describes the preparation of the southern perimeter DE segment, triene and deprotection model studies, and completion of the synthetic venture. Notable features of the approach include stereoselective σ-bond constructions of trisubstituted olefins and the union of advanced intermediates via efficient dithiane couplings.",10.1021/ja963066w,1997-02-01,0.605138604113493
Journal of Organic Chemistry,"A New, Facile Synthesis of 1,4,7,10-Tetraazacyclododecane:  Cyclen","This report outlines a new and efficient synthesis of cyclen (1,4,7,10-tetraazacyclododecane, 1) utilizing bis-imidazoline, 6 (1,1'-ethylenedi-2-imidazoline), with 1,2-dibromoethane. General conditions were developed, allowing for the simple, three-step synthesis of 1 at the multigram scale with an isolated overall yield approaching 65%. The cyclization of 6 produced by the condensation of triethylene tetraamine (TETA) with N,N-dimethylformamide dimethyl acetal, gave the twelve-membered, imidazolinium, cyclized intermediate bromide salt, 7 (2,3,4,5,6,7,8,8c-octahydro-1H-4a,6a,8a-triaza-2a-azoniacyclopent[fg]acenaphthylene), which hydrolyzed to 1 with the use of hot, aqueous caustic. Hydrolysis of 7 under milder conditions formed the 1,4,7,10-tetraazabicyclo[8.2.1]tridecan-13-one (20). Mechanistically, the formation of 7 may be rationalized as involving a diaminocarbene that undergoes an intramolecular carbon-hydrogen insertion.",10.1021/jo016111d,2002-05-18,0.6051369638227222
Synlett,"Facile One-Pot Synthesis of Novel 6-Monosubstituted 5,11-Dihydroindolo[3,2-<i>b</i>]carbazoles and Preparation of Different Derivatives","The synthesis of novel 6-monosubstituted 5,11-dihydroindolo[3,2-b]carbazoles was accomplished by a three-stage one-pot procedure involving condensation of indole and an aldehyde ­affording 3,3′-bis(indolyl)methanes, followed by isomerization to the 2,3′-analogues and acid-catalyzed intramolecular reaction with triethyl orthoformate to give the corresponding 6-monosubstituted indolo[3,2-b]carbazoles in good overall yield. Different substitution patterns, such as N-alkylation, N-arylation, formylation and bromination, were successfully introduced, leading to the formation of novel substituted 5,11-dihydroindolo[3,2-b]carbazole derivatives.",10.1055/s-2006-944183,2006-06-01,0.6051368629394734
Organic Letters,A Highly Convergent Approach toward (−)-Brevenal,"Progress toward a highly convergent, asymmetric synthesis of brevenal is reported. Construction of the AB-ring and E-ring cyclic ether fragments was achieved through asymmetric alkylation/ring-closing metathesis strategies. A Horner-Wadsworth-Emmons olefination was used in a key bond-forming step to couple the advanced cyclic fragments and enable rapid access to the AB-E ring system.",10.1021/ol1008203,2010-05-06,0.605135055895351
Organic Process Research & Development,"Development of an Efficient Process for 4,5,7-Trichloroquinoline, A Key Intermediate for Agrochemical Synthesis","A short, simple, and industrially feasible process for the preparation of 4,5,7-trichloroquinoline, starting from 3,5-dichloroaniline and acrylonitrile, in essentially three steps, is discussed. This article presents the preparative process, including the impurity profile, of each intermediate.",10.1021/op010111y,2002-04-06,0.6051333465714156
Tetrahedron,Total synthesis of polyamine amide spider toxin argiotoxin-636 by a practical reductive alkylation strategy,,10.1016/0040-4039(95)01994-s,1995-12-01,0.6051306087080836
Journal of Organic Chemistry,"Asymmetric Syntheses of APTO and AETD: the β-Amino Acid Fragments within Microsclerodermins C, D, and E","Efficient asymmetric syntheses of APTO and AETD, the highly functionalized β-amino acid fragments within microsclerodermins C, D, and E, are reported. The conjugate addition of lithium (R)-N-benzyl-N-(α-methylbenzyl)amide to tert-butyl (E,E)-7-(triisopropylsilyloxy)hepta-2,4-dienoate and in situ enolate oxidation with (-)-camphorsulfonyloxaziridine, diastereoselective dihydroxylation of a 2,3-syn-γ,δ-unsaturated-α-hydroxy-β-amino ester derivative under Donohoe conditions, and a Julia-Kocieński olefination were used as the key steps.",10.1021/jo302731m,2013-02-05,0.6051299868983532
Journal of the American Chemical Society,"Total Synthesis of the α-Glucosidase Inhibitors Schulzeine A, B, and C and a Structural Revision of Schulzeine A","The enantioselective total synthesis of the potent alpha-glucosidase inhibitors schulzeine A, B, and C and a revision of the proposed C20' configuration of schulzeine A are reported. The central feature of our convergent route to this family of novel marine natural products is the preparation of the common benzo[a]quinolizidine subunit through a substrate-controlled, diastereoselective Pictet-Spengler cyclocondensation.",10.1021/ja9005755,2009-04-08,0.6051253868386782
Journal of Organic Chemistry,Synthesis of Plagiochiline N from Santonin,"This article reports the transformation of O-acetylisophotosantonin, obtained by photochemical rearrangement of santonin, into plagiochiline N, an ent-2,3-secoaromadendrane isolated from Plagiochila ovalifolia. The synthesis was carried out in a sequence involving as the key steps (a) the substitution of the lactone moiety by a gem-dimethylcyclopropane ring through a synthetic intermediate having a C(6)-C(7) double bond and (b) the ozonolysis of the C(2)-C(3) bond followed by cyclization to the dihydropyran ring characteristic of plagiochiline N. Spectroscopic data of the synthetic product fully coincided with the reported data for the natural product.",10.1021/jo010567d,2001-10-24,0.6051253028507484
Tetrahedron,Enantioselective synthesis of methyl 2-[1-[( tert -butoxycarbonyl)amino]ethyl]-4-methyloxazole-5-carboxylate by a one–pot enamide cyclization,,10.1016/j.tetlet.2017.08.003,2017-08-02,0.6051216391931071
Tetrahedron,"A facile synthesis of 4-(sulfonylmethyl)indoles from 4-oxo-4,5,6,7-tetrahydroindole: Formal total synthesis of 6,7-secoagroclavine",,10.1016/s0040-4039(00)84745-0,1986-01-01,0.6051132495550836
Journal of Organic Chemistry,Synthesis of the Branched-Chain Sugar Aceric Acid:  A Unique Component of the Pectic Polysaccharide Rhamnogalacturonan-II,"Described herein is the synthesis of 3-C-carboxy-5-deoxy-L-xylose (aceric acid), a rare branched-chain sugar found in the complex pectic polysaccharide rhamnogalacturonan-II. The key synthetic step in the construction of aceric acid was the stereoselective addition of 2-trimethylsilyl thiazole to 5-deoxy-1,2-O-isopropylidene-alpha-L-erythro-pentofuran-3-ulose (2), which was prepared from L-xylose. The thiazole group was efficiently converted into the required carboxyl group via conventional transformations. Aceric acid was also synthesized by dihydroxylation of a 3-C-methylene derivative of 2 followed by oxidation of the resulting hydroxylmethyl group. The C-2 epimer of aceric acid was also synthesized using thiazole addition chemistry, starting from L-arabinose.",10.1021/jo051012b,2005-09-09,0.605105950384529
Angewandte Chemie International Edition,Construction of Axially Chiral Dialdehydes via Rhodium‐Catalyzed Enantioselective C−H Amidation,"Achieving axially chiral biaryl dialdehydes through asymmetric catalysis remains significantly challenging due to the lack of efficient strategies. In this report, we developed a rhodium-catalyzed enantioselective C-H amidation through chiral transient directing group strategy. With this new approach, a series of axially chiral amido dialdehydes were achieved in up to 86 % yields with 99.5 : 0.5 er. Furthermore, detailed mechanistic studies indicated that both the imine formation and C-H bond cleavage steps were reversible. More interestingly, the X-ray crystallographic analysis of Int-2 showed probable C-H/π interaction between biaryl group and chiral amine moiety. This process offered a convenient route to access axially chiral dialdehyde derivatives. More broadly, it demonstrated a new tool through transient and C-H/π synergistic interactions, which would stimulate further development of asymmetric catalytic system in enantioselective C-H functionalization.",10.1002/anie.202421412,2025-01-24,0.605099564819188
Organic Letters,First Highly Stereoselective Synthesis of Fungicide Systhane,"[reaction: see text] Highly enantiopure (R)-2-p-chlorophenyl-2-(1H-1,2,4-triazol-1-ylmethyl)hexanenitrile 1 (myclobutanil or systhane) was obtained in six synthetic steps from commercially available 1-hexyne (35% yield, 92% ee). The sulfinyl group controls the two key steps of the synthetic sequence, the highly stereoselective hydrocyanation of vinyl sulfoxides with Et(2)AlCN and the further introduction of the proper functionality into the molecule.",10.1021/ol0168723,2001-12-11,0.6050984425692777
Organic Letters,Practical Syntheses of Proposed and Revised Manzacidin B and Their Congeners,"A concise and highly stereoselective total synthesis of manzacidin B and its congeners has been developed following chelation-controlled syn-epoxidation and Lewis acid catalyzed intramolecular regioselective epoxide ring opening to generate the quarternary amine center. Elaboration of the triol moiety to the target molecule was achieved in good overall yield, representing practical total syntheses of manzacidin B and its congeners. From the XRD, NMR, and analytical data, the correct structure of natural manzacidin B, (4R,5R,6R)-6, was confirmed.",10.1021/ol203466m,2012-02-08,0.6050872850833172
Journal of Organic Chemistry,An Oxazoline-Mediated Synthesis of the Pyrrolophenanthridine Alkaloids and Some Novel Derivatives,"An unsymmetrical biaryl coupling between the Grignard of N -benzyl-7-bromoindoline 25 and the appropriately substituted ( o -methoxyaryl)oxazoline 15 leads to an intermediate biaryl which can be elaborated in one step to the 1 H -pyrrolo[3,2,1- de ]phenanthridine ring system. This simple two-step sequence provides general access to the pyrrolophenanthridine alkaloids 2 − 6 .",10.1021/jo951474x,1996-01-01,0.6050853687830856
Organic Letters,"Total Syntheses of (±)-Rhodonoids C, D, E, F, and G and Ranhuadujuanine B","Here we describe the divergent, biosynthetically inspired syntheses of (±)-rhodonoids C-G and (±)-ranhuadujuanine B. The key steps of the syntheses include the construction of the chromene unit through a formal oxa-[3 + 3] annulation and a biomimetic acid-catalyzed ring cyclization. Cationic [2 + 2] cycloaddition is accomplished to form the cyclobutane core of (±)-rhodonoids E and F.",10.1021/acs.orglett.7b01463,2017-06-12,0.605074835314545
Organic Letters,Stereoselective Synthesis of 7-<i>epi</i>-Incarvilline,"The enantioselective synthesis of 7-epi-incarvilline for formal syntheses of (-)-incarvilline, (+)-incarvine C, and (-)-incarvillateine is described. The key features of our synthesis involve (1) stereoselective construction of the optically active bicyclic lactone utilizing Pd(0)-catalyzed allylic alkylation, (2) efficient transformation of the bridged bicyclic lactone to the key bicyclic lactam skeleton, and (3) stereoselective elaborations of two stereocenters via a substrate-controlled catalytic hydrogenation and a 1,4-addition.",10.1021/ol303395f,2013-01-23,0.605064112583252
Journal of Organic Chemistry,Concise Formal Synthesis of (−)-Salinosporamide A (Marizomib) Using a Regio- and Stereoselective Epoxidation and Reductive Oxirane Ring-Opening Strategy,"Expedient access to a highly functionalized 2-pyrrolidinone (8), the gamma-lactam core of 20S proteasome inhibitor (-)-salinosporamide A (marizomib; NPI-0052; 1), using a regio- and stereoselective epoxide formation/reductive oxirane ring-opening strategy is presented. Notably, the sequential construction of the C-4, C-3, and C-2 stereocenters of 1 in a completely stereocontrolled fashion is a key feature of streamlining the synthesis of intermediate 12. A related strategy is also discussed.",10.1021/jo100432g,2010-05-14,0.605053454703696
Synlett,Novel Serotonin-3 Receptor Antagonists,"All articles of this category A structurally novel series of serotonin-3 (5-HT 3 ) receptor antagonists is described. A computer pharmacophore model for ligands binding to this receptor has been developed and utilized to explain observed structure-activity relationships as well as demonstrated predictive utility. A novel azabicyclic 5-HT 3 receptor ligand prototype [2-(4-amino-5-chloro-2-methoxybenzamidomethyl)-1-azabicyclo[2.2.2]oct-2-ene] has also been discovered, and its selective synthesis, which proceeds through a thermodynamically disfavored allylic azide, is described. 1. Introduction 2. Biological Assays - Definitions 3. Discovery of the Lead Structure 7 (3-[2-(Guanidinomethyl)-1,3-thiazol-4-yl]indole) and Approach to Its Modification 4. Definition and Application of an Initial Computer Pharmacophore Model for Selective 5-HT 3 Receptor Ligands 5. Structure - Activity Relationship (SAR) Studies 6. Synthesis of a Novel Azabicyclic Prototype 7. Summary",10.1055/s-1991-20683,1991-01-01,0.6050527716145943
Organic Letters,Total Synthesis of Termicalcicolanone A via Organocatalysis and Regioselective Claisen Rearrangement,"A total synthesis of an anticancer xanthone natural product termicalcicolanone A utilizing multiple nucleophilic aromatic substitutions and pericyclic reactions has been developed. The pyrano[3,2- b]xanthen-6-one scaffold was constructed via NHC-catalyzed aroylation to produce the benzophenone intermediate, Claisen cyclization to form the pyran ring, and intramolecular 1,4-addition to construct the xanthone framework. The prenyl group was introduced in the final stages of the synthesis through regioselective Claisen rearrangement. The synthesis has been achieved in 19 steps.",10.1021/acs.orglett.9b00731,2019-04-08,0.605051647019994
Journal of Organic Chemistry,"Organocatalytic Asymmetric Synthesis of SynVesT-1, a Synaptic Density Positron Emission Tomography Imaging Agent","High Resolution Image Download MS PowerPoint Slide Heterocyclic nonacetamide ligands are used as positron emission tomography (PET) imaging agents of the synaptic vesicle glycoprotein 2A (SV2A), with potential applications in the diagnosis of various neuropsychiatric diseases. To date, the main synthetic strategy to access these optically active compounds has involved the racemic synthesis of a late-stage intermediate followed by the separation of the enantiomers. Here, we describe the use of iminium organocatalysis for the asymmetric synthesis of SynVesT-1, an important PET imaging agent of SV2A. The key step involved the conjugate addition of nitromethane with a cinnamaldehyde in the presence of the Jørgensen–Hayashi catalyst using the Merck dual acid cocatalyst system. Pinnick-type oxidation and esterification of the adduct was then followed by chemoselective nitro group reduction and cyclization using nickel borate. N -Alkylation of the resulting lactam then completed the seven-step synthesis of SynVesT-1. This approach was amenable for the synthesis of an organotin analogue, which following copper(II)-mediated fluoro-destannylation allowed rapid access to [ 18 F]SynVesT-1.",10.1021/acs.joc.2c01895,2022-10-12,0.6050476219263966
European Journal of Organic Chemistry,"Stereospecific, Flexible and Redox‐Economic Asymmetric Synthesis of <i>cis</i>‐ and <i>trans</i>‐3‐Hydroxypipecolic Acids and Analogs","Abstract Both cis ‐ and trans ‐3‐hydroxy‐ L ‐pipecolic acids are synthesized from a common chiral intermediate 7 by a short and flexible route. The stereospecific inversion of C‐3 was achieved by the formation of an oxazoline followed by acidic ring cleavage. The overall yields are 27 % and 30 %, respectively, in 12 and 10 linear steps. Several versatile chiral building blocks are also accessible by this diastereodivergent synthesis. Unlike the chiral pool approach, our synthetic strategy is not limited by the availability of starting materials.(© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2009)",10.1002/ejoc.200900231,2009-04-21,0.6050419138384283
Organic Letters,Diastereoselective Total Synthesis of Raputindole A,"The first diastereoselective total synthesis of the bisindole alkaloid raputindole A is reported. After Au(I)-catalyzed assembly of the cyclopenta[ f]indole tricycle, it was possible to hydrogenate the indene double bond regio- and diastereoselectively through iridium catalysis, guided by a preinstalled hydroxy function. Attempted HWE reaction led to formal elimination of formaldehyde from an α-quaternary cyclopentane carbaldehyde, which was circumvented by Takai olefination. After Suzuki-Miyaura cross coupling and deprotection/oxidation, (±)-raputindole A was obtained in 13 linear steps in 18% overall yield.",10.1021/acs.orglett.8b02349,2018-08-28,0.6050396345273623
Angewandte Chemie International Edition,An Asymmetric Hydrogenation/N‐Alkylation Sequence for a Step‐Economical Route to Indolizidines and Quinolizidines,"The direct catalytic asymmetric hydrogenation of pyridines for the synthesis of piperidines remains a challenge. Herein, we report a one-pot asymmetric hydrogenation of pyridines with subsequent N-alkylation using a traceless Brønsted acid activation strategy. Catalyzed by an iridium-BINAP complex, the substrates undergo ketone reduction, cyclization and pyridine hydrogenation in sequence to form indolizidines and quinolizidines. The absolute configuration of the stereocenter of the alcohol is retained and influences the formation of the second stereocenter. Experimental and theoretical mechanistic studies reveal that the chloride anion and certain noncovalent interactions govern the stereoselectivity of the cascade reaction throughout the catalytic process.",10.1002/anie.202308836,2023-08-30,0.6050348169185281
Angewandte Chemie International Edition,"Heteroannulation of Arynes with α‐Amino Imides: Synthesis of 2,2‐Disubstituted Indolin‐3‐ones and Application to the Enantioselective Total Synthesis of (+)‐Hinckdentine A","A novel heteroannulation reaction between α-amino imides and in situ generated arynes has been developed for the synthesis of 2,2-disubstituted indolin-3-ones. An enantioselective total synthesis of the marine alkaloid (+)-hinckdentine A was subsequently accomplished using this reaction as a key step. A catalytic enantioselective Michael addition of an α-aryl-α-isocyanoacetate to phenyl vinyl selenone was employed for the construction of the enantioenriched α-quaternary α-amino ester.",10.1002/anie.201800746,2018-03-30,0.605024448391039
Organic Process Research & Development,Efficient Multikilogram Synthesis of 5-Bromo-2-cyclopropyl-1-methyl-1<i>H</i>-imidazole,"Herein we describe the optimization and application of a copper(I) chloride-mediated protocol for the multikilogram synthesis of 5-bromo-2-cyclopropyl-1-methyl-1 H -imidazole hydrochloride ( 1 ), a key building block used in the preparation of several biologically active small molecules.",10.1021/op700195j,2007-10-27,0.6050232905535172
Synlett,Annulations of 5-Phenylthiobutenolides and First Synthesis of (±)-Indanostatin,"The first synthesis of indanostatin was achieved in 6 steps. Key steps included a butenolide annulation, oxidation to an indanetrione, and reaction with acetone.",10.1055/s-0037-1611462,2019-01-10,0.6050196338016355
Synlett,Adventures in Total Synthesis – The Next Chapter,"Abstract This account summarizes the author’s endeavors in target-oriented synthesis at Seoul National University since 2011. A collection of the most celebrated molecules in total synthesis are revisited and the author’s solutions to these historical challenges are presented. In particular, the unique perception of their molecular frameworks and unprecedented bond-forming sequences form the basis of the newly developed strategies. Together with a ‘personal touch’ on these selected stories, the author hopes that this account will offer new insights and fresh perspectives for all levels of enthusiasts of target-oriented total synthesis. 1 Introduction 2.1 Synthesis of Strychnine 2.2 Synthesis of Actinophyllic Acid 2.3 Synthesis of Dendrobine 2.4 Synthesis of Communesin 2.5 Synthesis of Morphinans 2.6 Synthesis of Reserpine 2.7 Synthesis of Quinine and Quinidine 2.8 Synthesis of Haouamine 2.9 Future Work 3 Summary and Outlook 4 Abbreviations",10.1055/a-2145-3647,2023-07-31,0.6050158672404418
Journal of the American Chemical Society,Unified Total Synthesis of <i>C</i> <sub>2</sub> -Symmetric Bis(cyclotryptamine) Alkaloids Utilizing a Single-Atom Insertion/Deletion Strategy,"High Resolution Image Download MS PowerPoint Slide Strategies for total synthesis have advanced alongside the development of new methodologies, thereby enabling access to structurally intricate molecules that were previously difficult to obtain. Here, we present a strategy for the synthesis of bis(cyclotryptamine) alkaloids inspired by methods for single-atom insertion/deletion. To implement our plan, we first pursued the synthesis of tetrahydropsychotriadine ( 4 ), an isomer of calycanthine ( 1 ), which was achieved in 9 steps and set the stage for the preparation of calycanthine ( 1 ), chimonanthine ( 2 ), and psychotriadine ( 6 ). Our studies, driven by calculations, also provide the first access to a natural product bearing the pyrrolidinoquinoline scaffold, CPC-2 ( 29 ). Finally, we resolve a long-standing misassignment of the structure of the natural product dubbed isocalycanthine. En route to our synthesis of 4, we establish a methodology for the construction of unprecedented diaryl-substituted cis- and trans-fused 5,5-bicycles using a photodecarbonylation. The mechanism for the trans-selective formation of 5,5-bicycles is investigated by using DFT calculations.",10.1021/jacs.5c15181,2025-12-11,0.6050080802847002
Tetrahedron,Synthesis of ethyl 1-azabicyclo[2.2.1]hept-4-yl carboxylate,,10.1016/s0040-4039(00)92056-2,1991-02-01,0.6049948852989
Synthesis,A Novel Short Approach to (<i>Z</i>)-Pulchellalactam through Transition-Metal-Catalyzed Atom-Transfer Radical Cyclization of 1-Isopropylprop-2-enyl Dichloroacetate,"A new, five-step route to (Z)-pulchellalactam, a CD45 protein tyrosine phosphatase inhibitor, is presented. Key steps are the copper(I) chloride-bipyridyl catalyzed atom-transfer radical cyclization­ of an appropriate allyl α,α-dichloroacetate and the subsequent dehydrochlorination/prototropic rearrangement of the resulting dichlorolactone.",10.1055/s-2007-983709,2007-06-01,0.6049931844465982
Organic Letters,Preparation of a Functionalized Tetracyclic Intermediate for the Synthesis of Rhodexin A,"An efficient synthesis of the tetracyclic steroid core, 19, of rhodexin A and sarmentogenin is reported. An initial inverse-electron-demand Diels-Alder reaction of the acyldiene 6 with the silyl enol ether 7a gave the cycloadduct 8 with the required four contiguous stereocenters in a single step. This compound was then transformed into the methylated enedione 13 which afforded after a reductive alkylation and annulation sequence the tetracycle 19.",10.1021/ol801426z,2008-07-22,0.604992967533754
Tetrahedron,"Asymmetric total synthesis of (2S,3S)-3-hydroxypipecolic acid",,10.1016/j.tetlet.2010.11.062,2010-11-20,0.6049924769629462
Organic Letters,Synthesis of a Tricyclic Mescaline Analogue by Catalytic C−H Bond Activation,[reaction: see text] A tetrahydrobis(benzofuran) mescaline analogue has been prepared in six steps and 38% overall yield from (4'-O-methyl)methyl gallate. The key step in this synthesis is a tandem cyclization reaction via directed C[bond]H activation followed by olefin insertion.,10.1021/ol034228d,2003-03-22,0.6049898364499795
Journal of Organic Chemistry,Me-DuPHOS-Rh-Catalyzed Asymmetric Synthesis of the Pivotal Glutarate Intermediate for Candoxatril,"A greatly improved process has been developed for synthesis of the glutarate derivative 2, a key intermediate required for Pfizer's drug candoxatril. The cationic (R,R)-Me-DuPHOS-Rh catalyst was found to allow highly efficient and enantioselective hydrogenation of a unique carboxylate substrate (5) to afford the desired product in >99% ee and high yield (95%). The robust nature of the process was validated on a 12 kg reaction scale. A novel mechanism for the hydrogenation process is proposed. Through use of a labile eta(6)-benzene-Rh-Me-DuPHOS complex, the postulated catalytic intermediates have been synthesized by independent means. Detailed spectroscopic analyses of these intermediates corroborate the mechanistic hypotheses. Interconversion of these key catalytic intermediates has been demonstrated.",10.1021/jo990145s,1999-04-01,0.6049779485709579
Synlett,"Concise Synthesis of 1,4-Dideoxy-1,4-imino-l-arabinitol (LAB) from d-Xylose by Intramolecular Stereospecific Substitution of a Hydroxy Group","Abstract We report a concise and green total synthesis of 1,4-dideoxy-1,4-imino-l-arabinitol hydrochloride from naturally occurring d-xylose. The key step involves a stereospecific substitution of a hydroxy group, without prior derivatization, in which the only byproduct is water. This opens up a novel benign route to iminosugar derivatives with diverse biological activities.",10.1055/s-0041-1738432,2023-02-15,0.604970515493145
Journal of Organic Chemistry,Reaction of Highly Methylated 2-Methylenecycloalkyl Hydroperoxides with FeSO<sub>4</sub>/CuCl<sub>2</sub>. Remarkably Efficient 5-<i>e</i><i>ndo</i>-<i>t</i><i>rig</i>or 6-<i>e</i><i>ndo</i>-<i>t</i><i>rig</i>Cyclization of the Intermediate Carbon Radicals,"Treatment of 1,3,3,4,4,5,5-heptamethyl-2-methylenecyclopentyl hydroperoxide, derived from a singlet oxygen ene reaction of 1,2,3,3,4,4,5,5-octamethylcyclopentene, with FeSO 4 /CuCl 2 gave 1-chloro-2,2,3,3,4,4-hexamethylcyclopentyl methyl ketone in high yield, suggesting that the consecutive O−O and C−C bond fission is followed by a novel 5- endo - trig cyclization of the intermediate carbon radical to the activated C−C double bond. In the case of 1,3,3,6,6-pentamethyl-2-methylene-1-cyclohexyl hydroperoxide also, an efficient 6- endo - trig cyclization of the corresponding carbon radical was realized giving 1-chloro-2,2,5,5-tetramethylcyclohexyl methyl ketone in high yield.",10.1021/jo990127a,1999-05-01,0.6049694864202899
Synthesis,Concise Total Syntheses of Paullone and Kenpaullone via Cyanide-Catalyzed Intramolecular Imino-Stetter Reaction,Highly concise total syntheses of paullone and kenpaullone were developed. Cyanide-catalyzed intramolecular imino-Stetter reaction of aldimines derived from methyl 2-aminocinnamate derivatives and 2-nitrobenzaldehyde provided 2-(2′-nitrophenyl)indole-3-acetic acid derivatives. Subsequent reduction of the nitro group with zinc under acidic conditions to an amino group followed by spontaneous lactam formation allowed for the total syntheses of paullone and kenpaullone to be completed in two steps starting from commercially available materials. The direct use of a nitro group as the precursor of an amino group present in the phenyl ring at the 2-position in the indole ring significantly streamlined the total syntheses of these target molecules.,10.1055/s-0036-1588749,2017-03-14,0.6049675535250705
Tetrahedron,A new approach to the synthesis of oligomers. Application to the synthesis of p-phenylene thioether wires,,10.1016/j.tetlet.2005.06.143,2005-07-18,0.6049552806261789
Journal of Organic Chemistry,Construction of Chiral Cyclobutanone-Fused 4-Aminoquinolines via Sequential Chiral Phosphoric Acid and Palladium Catalysis,"A one-pot catalytic asymmetric route to novel chiral quaternary-carbon-containing cyclobutanone-fused 4-aminoquinoline derivatives in good to high yields and enantioselectivities is described. This process consists of a chiral phosphoric acid-catalyzed desymmetric carbonyl-amine condensation of prochiral cyclobutane-1,3-diones with 2-halogenated anilines and a Pd-catalyzed coupling reaction of the chiral enaminone intermediates with isocyanides.",10.1021/acs.joc.3c00098,2023-03-23,0.6049542653405776
Synlett,"Total Synthesis of 22,23-Dihydroavermectin B<sub>1b</sub>Aglycone","All articles of this category The total synthesis of the aglycone of 22,23-dihydroavermectin B 1b involves a palladium(0) catalysed cross-coupling reaction between a C10-C25 northern E -vinylstannane and a C1-C9 vinyl iodide where the Δ 3 double bond as well as the correct stereochemistry at C - 2 are already present. The final steps include successive deprotection of the carboxyl β-(trimethylsilyl)ethyl protecting group of the intermediate secoester, macrolactonisation and acidic hydrolysis of 5- O - tert -butyldimethylsilyl residue to give the title aglycone.",10.1055/s-1991-20815,1991-01-01,0.6049529042442202
Tetrahedron,A new highly diastereoselective synthesis of epi-inositol from d-galactose,,10.1016/s0040-4039(00)00360-9,2000-04-01,0.604947937526251
Green Chemistry,Highly efficient synthesis of β-nitrate ester carboxamides through the ring-opening of 2-oxazolines,A novel method for the synthesis of β-nitrate ester carboxamides using non-corrosive <italic>tert</italic> -butyl nitrite (TBN) as the nitro source and easily available oxygen as the oxidant has been developed.,10.1039/c7gc02682j,2017-01-01,0.6049440996933154
Tetrahedron,The baeyer-villiger oxidation of δ4-3-ketosteroids: A route to some novel a-norsteroids,,10.1016/s0040-4039(00)90003-0,1965-01-01,0.6049359375360506
Organic Process Research & Development,An Improved and Single Pot Process for the Production of Quetiapine Hemifumarate Substantially Free from Potential Impurities,"An improved and single pot process for the preparation of Quetiapine hemifumarate ( 1 ), an antipsychotic drug, free from potential impurities is reported with an overall yield of 80%. The reported process for its preparation suffers from the drawback of producing potential impurities identified as 11-piperazin-1-yldibenzo[ b, f ][1,4]thiazepine ( 6 ), 2-(4-dibenzo[ b, f ][1,4]thiazepin-11-ylpiperazin-1-yl)ethanol ( 10 ), dimer ( 9 ), and N -methyl- N -phenyldibenzo[ b,f ][1,4]thiazapine-11-amine ( 14 ). Elimination of these impurities in the process is achieved by chlorination of 3 followed by in situ condensation of obtained 4 with highly pure 8 and subsequently establishing the pH based workup to obtain free base 2, which is further converted to quetiapine hemifumarate salt free from all these impurities. In this report, different aspects of process development such as scheme selection, optimization of different process parameters, identification, synthesis, origin and control of impurities, and development of an accurate analytical method during the development of a scalable process for quetiapine hemifumarate are discussed.",10.1021/op900097q,2009-06-23,0.604929709411691
Angewandte Chemie International Edition,A Cascade Strategy Enables a Total Synthesis of (±)‐Morphine,"Morphine has been a target for synthetic chemists since Robinson proposed its correct structure in 1925, resulting in a large number of total syntheses of morphine alkaloids. Here we report a total synthesis of (±)-morphine that employs two key strategic cyclizations: 1) a diastereoselective light-mediated cyclization of an O-arylated butyrolactone to form a tricyclic cis-fused benzofuran and 2) a cascade ene-yne-ene ring closing metathesis to forge the tetracyclic morphine core. This approach enables a short and stereoselective synthesis of morphine in an overall yield of 6.6 %.",10.1002/anie.201608526,2016-10-13,0.6049269404489158
Angewandte Chemie International Edition,Total Synthesis of Indole Alkaloid Alsmaphorazine D,"A concise total synthesis of rac-alsmaphorazine D has been described for the first time. The efficient synthetic strategy features four key transformations: 1) a catalytic intramolecular oxidative cyclization for the δ-lactamindole backbone; 2) an oxidative cyclic aminal formation for the hexahydropyrrolo[2,3-b]pyrrole framework; 3) a transannular radical cyclization for the construction of the diazabicyclo[3.3.1]nonane structure; and 4) a one-pot desilylation/double epimerization reaction that affirms the relative stereochemistry.",10.1002/anie.201409827,2014-11-21,0.6049259891107223
Organic Letters,Asymmetric Total Synthesis of Nigerone,"[reaction: see text] An enantioselective synthesis of the chiral bisnaphthopyrone natural product nigerone is reported. The key step was an eight-step isomerization process to form the final natural product. The isomerization precursor was constructed via asymmetric oxidative biaryl coupling of an advanced intermediate with a 1,5-diaza-cis-decalin copper catalyst.",10.1021/ol062468y,2007-01-03,0.6049138150221205
European Journal of Organic Chemistry,"Total Synthesis of (2<i>RS</i>)‐α‐Tocopherol through Ni‐Catalyzed 1,4‐Addition to a Chromenone Intermediate","Abstract A novel strategy for the total synthesis of α‐tocopherol (“vitamin E”) was elaborated on the basis of the conjugate addition of AlMe 3 (as a methyl anion equivalent) to a 2‐substituted chromenone. Starting from trimethylhydroquinone and ( R , R )‐hexahydrofarnesol, the required chromenone substrate was efficiently prepared in a short sequence exploiting a TiCl 4 ‐mediated Fries rearrangement and a KO t Bu‐induced Baker–Venkatamaran rearrangement. The envisioned key step, which sets up the quaternary center at C2, was performed in virtually quantitative yield through Ni‐catalyzed conjugate addition of AlMe 3 . However, this transformation, which likely proceeds through a radical mechanism, could not be rendered stereoselective by means of chiral ligands. Nevertheless, the elaborated synthesis of (2 RS ,4′ R ,8′ R )‐α‐tocopherol ( 2 ‐ ambo ‐α‐tocopherol) is efficient and challenges the future development of suitable protocols for the asymmetric 1,4‐addition.",10.1002/ejoc.201402240,2014-04-17,0.604912765876013
Journal of the American Chemical Society,Total Syntheses of Amphidinolide X and Y,"Concise total syntheses of the cytotoxic marine natural products amphidinolide X (1) and amphidinolide Y (2) as well as of the nonnatural analogue 19-epi-amphidinolide X (47) are described. A pivotal step of the highly convergent routes to these structurally rather unusual secondary metabolites consists of a syn-selective formation of allenol 17 by an iron-catalyzed ring opening reaction of the enantioenriched propargyl epoxide 16 (derived from a Sharpless epoxidation) with a Grignard reagent. Allenol 17 was then cyclized with the aid of Ag(I) to give dihydrofuran 19 containing the (R)-configured tetrasubstituted sp3 chiral center at C.19, which was further elaborated into tetrahydrofuran 25 representing the common heterocyclic motif of 1 and 2. The aliphatic chain of amphidinolide X featuring an anti-configured stereodiad at C.10 and C.11 was generated by a palladium-catalyzed, Et2Zn-promoted addition of the enantiopure propargyl mesylate 29 to the functionalized aldehyde 28. The preparation of the corresponding C.1-C.12 segment of amphidinolide Y relies on asymmetric hydrogenation of an alpha-ketoester, a diastereoselective boron aldol reaction, and a chelate-controlled addition of MeMgBr in combination with suitable oxidation state management for the elaboration of the tertiary acyloin motif. Importantly, the end games of both total syntheses follow similar blueprints, involving key fragment coupling processes via the ""9-MeO-9-BBN"" variant of the alkyl-Suzuki reaction and final Yamaguchi esterifications to forge the 16-membered macrodiolide ring of amphidinolide X and the 17-membered macrolide frame of amphidinolide Y, respectively. This methodological convergence ensures high efficiency and an excellent overall economy of steps for the entire synthesis campaign.",10.1021/ja061918e,2006-06-24,0.6049093135171664
Organic Letters,Synthesis of Mono-<i>O</i>-alkylated Homooxacalix[3]arene and a Protection–Deprotection Strategy for Homooxacalix[3]arene,The regioselective synthesis of mono-O-alkylated homooxacalix[3]arene is accomplished for the first time. The synthetic route relies on two key steps: (i) a facile protection of two OH groups at the lower rim of the homooxacalix[3]arene and (ii) the deprotection of 9-anthrylmethyl groups via the Pd/C-catalyzed hydrogenation under atmospheric hydrogen. An efficient protection-deprotection strategy for the functionalization of homooxacalix[3]arene is presented.,10.1021/acs.orglett.6b03338,2016-12-12,0.604908448998101
Tetrahedron,"Concomitant ring contraction cyclization strategy for the synthesis of novel 4-oxo-4,5-dihydro-pyrroloquinolines",,10.1016/j.tetlet.2004.05.115,2004-07-01,0.6048991030513162
Synlett,A Practical Procedure for the Multigram Synthesis of the SuperQuat Chiral Auxiliaries,All articles of this category An efficient and simple synthesis of oxazolidin-2-one SuperQuat chiral auxiliaries is described which provides rapid access to multigram quantities of the auxiliaries. chiral auxiliaries - SuperQuat - Grignard addition,10.1055/s-1998-1700,1998-05-01,0.6048962962271873
Organic Letters,Total Synthesis of (±)-Leonuketal,"-labdane terpenoid with a unique tetracyclic structure, owing to a diversity-generating biosynthetic C-C bond cleavage event. The first total synthesis of leonuketal is reported, featuring a Ti(III)-mediated reductive cyclization of an epoxy nitrile ether, an unusual ring-opening alkyne formation as part of an auxiliary ring strategy, and the previously undescribed Au(I)-catalyzed cyclization of a β-keto(enol)lactone to assemble the core spiroketal motif.",10.1021/acs.orglett.0c03364,2020-10-21,0.6048874946892328
Organic Letters,Total Synthesis of (−)-Agelastatin A: The Application of a Sequential Sigmatropic Rearrangement,"An enantioselective total synthesis of (-)-agelastatin A from (-)-2,3-O-isopropylidene-d-threitol is described. The sequential Overman/Mislow-Evans rearrangement of the allylic bistrichloroimidate is the key step, which efficiently installed a diaminohydroxy group.",10.1021/ol900799e,2009-05-18,0.6048867452483166
Organic Letters,Total Synthesis of Citridone A,The first total synthesis of citridone A has been achieved through regioselective intramolecular iodocyclization and regio- and stereoselective Pd(0)-catalyzed coupling as key reactions.,10.1021/ol200022a,2011-02-09,0.6048840415984726
Journal of Organic Chemistry,Enantioselective Syntheses of Monotetrahydrofuran Annonaceous Acetogenins Tonkinecin and Annonacin Starting from Carbohydrates,"The total synthesis of two mono-THF acetogenins, tonkinecin (1) and annonacin (2), is reported in full detail. Terminal acetylene 3 prepared from D-glucono-delta-lactone and asymmetric dihydroxylation was employed as a common intermediate for both targets 1 and 2. Pd(0)-catalyzed coupling reaction of 3 with vinyl iodides 4 and 5, the chiral centers of which were taken from D-xylose and S-(-)-ethyl lactate, afforded enyne 26 and 27, respectively. Selective hydrogenation of 26 or 27 with diimide followed by removal of MOM ethers completed the synthesis of 1. A coupling reaction between the lithium derivative of 3 and epoxide 6 in the presence of boron trifluoride etherate gave 42. Both chiral centers in epoxide 6 were taken from L-ascorbic acid. Subsequent catalytic hydrogenation and MOM protection led to 43b. Introduction of the butenolide moiety by aldol condensation of protected S-lactal followed by cleavage of all MOM ethers completed the synthesis of 2.",10.1021/jo005643b,2000-12-21,0.6048733250872232
Tetrahedron,Zirconium-catalyzed enantiotopic group-selective synthesis of hydrindanes,,10.1016/s0040-4039(03)00780-9,2003-04-25,0.604862416125715
Angewandte Chemie International Edition,Efficient Synthesis and Resolution of Pyrrolizidines,In only two steps the commercially available maleimide 1 is converted into the key pyrrolizidine carboxylic acid unit (2) of the telomerase inhibitor UCS1025A. A kinetic resolution through an enantioselective oxa-Michael lactonization and trituration of the resulting scalemic mixture allow for a virtually quantitative separation of a racemate into the enantiomers.,10.1002/anie.200605035,2007-03-06,0.6048506396152936
Journal of the American Chemical Society,Total Synthesis of Eleutherobin and Eleuthosides A and B,"The total synthesis of the cytotoxic marine natural products eleutherobin ( 1 ) and eleuthosides A ( 2 ) and B ( 3 ) is described. The strategy involves glycosidation of the (+)-carvone-derived intermediate 7 with the arabinose-derived trichloroacetimidate 9 followed by base-induced ring closure and elaboration to afford the dihydroxy eneynone 19 . Selective hydrogenation of 19 led to the generation and intramolecular collapse of dienone 20 furnishing 21 and thence 22 with the required structural framework of the target molecules. Finally, esterification with mixed anhydride 24 followed by deprotection gave eleutherobin ( 1 ) which served as a precursor to eleuthosides A ( 2 ) and B ( 3 ). The α-glycoside anomer of eleutherobin, compound 27, was also synthesized by application of the developed chemistry, demonstrating the flexibility of the sequence in generating designed analogues for biological screening.",10.1021/ja9810639,1998-08-13,0.6048483611031792
Organic Letters,Linear Amine-Linked Oligo-BODIPYs: Convergent Access via Buchwald–Hartwig Coupling,"A convergent route toward nitrogen-bridged BODIPY oligomers has been developed. The synthetic key step is a Buchwald-Hartwig cross-coupling reaction of an α-amino-BODIPY and the respective halide. Not only does the selective synthesis provide control of the oligomer size, but the facile preparative procedure also enables easy access to these types of dyes. Furthermore, functionalized examples were accessible via brominated derivatives.",10.1021/acs.orglett.4c00827,2024-04-02,0.6048406305212727
Chemical Science,Total synthesis of biselide A,"A total synthesis of the marine macrolide biselide A is described that relies on an enantiomerically enriched α-chloroaldehyde as the sole chiral building block. Several strategies to construct the macrocycle are presented including a macrocyclic Reformatsky reaction that ultimately provides access to the natural product in a longest linear sequence of 18 steps. Biological testing of synthetic biselide A suggests this macrolide disrupts cell division through a mechanism related to the regulation of microtubule cytoskeleton organization. Overall, this concise synthesis and insight gained into the mechanism of action should inspire medicinal chemistry efforts directed at structurally related anticancer marine macrolides.",10.1039/d0sc06223e,2021-01-01,0.6048376588011912
Synthesis,"A Convenient One-Step Synthesis of 2-Isopropylfuro[2,3-<i>b</i>] quinolines from 3-Prenyl-2-quinolones","All articles of this category An efficient one-step procedure for the synthesis of 2-isopropylfuro[2,3- b ] quinolines consists of treatment of 3-prenyl-2-quinolones with iodine/HgO in acetic acid.",10.1055/s-1989-27394,1989-01-01,0.6048352268951516
Synthesis,"An Efficient and Convenient Protocol for the Synthesis of 1,1-Difluoro-6-nitro-2,3-dihydro-1H-indene Derivatives","A convenient and efficient synthesis of gem -difluorinated compounds is reported. The synthetic route toward various 2-substituted and 3-substituted 1,1-difluoro-6-nitro-2,3-dihydro-1 H -indene derivatives is described starting from commercially available indanone. The key gem -difluorination step is accomplished in good yield by treatment of in situ generated bromine fluoride (BrF) with a dithioketal. A plausible mechanism discussing the competition between substitution and elimination is provided to rationalize the outcome of the reactions of the 3-brominated compounds with different amines.",10.1055/s-0033-1340595,2014-01-23,0.6048281163386187
Angewandte Chemie International Edition,"Asymmetric Total Synthesis of Solandelactone E: Stereocontrolled Synthesis of the 2‐ene‐1,4‐diol Core through a Lithiation–Borylation–Allylation Sequence","A highly stereoselective, 13-step synthesis of solandelactone E is reported which employs the lithiation–borylation–allylation sequence as the key step (see scheme). This synthetic method solves the problem of poor stereocontrol at C11 that had dogged many previous syntheses of this class of molecules.",10.1002/anie.201003236,2010-08-03,0.6048270459249016
Organic Process Research & Development,An Efficient Synthesis of 3-Substituted <i>N</i>-Glycoside Indoles Useful as Sodium-Dependent Glucose Transporter Inhibitors,"A practical synthesis of two N -glycoside indoles 1 and 2, identified as highly potent sodium-dependent glucose transporter (SGLT) inhibitors is described. Highlights of the synthetic process include a selective and quantitative Vilsmeier acylation and a high-yielding Grignard coupling reaction. The chemistry developed has been applied to prepare two separate SGLT inhibitors 1 and 2 for clinical evaluation without recourse to chromatography.",10.1021/op3001355,2012-10-19,0.6048243180705541
Synthesis,A Convenient Access to Chiral Monofunctionalized Bicyclic Guanidinium Receptor Groups,"All articles of this category An easy and high-yield route for the preparation of functional and chiral hexahydropyrimido[1,2- a ]pyrimidines 3 is described. Starting from known methioninol and 2-methylmercaptotetrahydropyrimidine 5 , the target compounds, which may be useful as building blocks in the synthesis of polymodular molecular hosts, were obtained in over 50% total yield. As an example the iodo compound 20 was converted into the homoarginine analog 22 in 70% yield. molecular recognition - anion host - guanidine - amino acid - chiral pyrimido[1,2a]pyrimidine",10.1055/s-1995-3953,1995-05-01,0.6048209853162627
Angewandte Chemie International Edition,Total Synthesis of (±)‐Merrilactone A,"An efficient total synthesis of (±)-merrilactone A has been accomplished, featuring: 1) a Johnson–Claisen rearrangement and the subsequent deprotection–lactonization to generate the A ring, 2) an intramolecular hetero-Pauson–Khand reaction to construct the B and D rings, and 3) a vinylogous Mukaiyama–Michael reaction and reductive carbonyl–alkene coupling to assemble the C ring.",10.1002/anie.201200378,2012-05-04,0.6048171097756992
Tetrahedron,A norbornyl route to azasugars: stereoselective synthesis of isofagomine analogues,,10.1016/s0040-4039(00)00896-0,2000-07-01,0.6048057773108184
Synthesis,"A Convenient Synthesis of the Pyrrolo[3,2-<i>c</i>]quinoline Core of Martinelline Alkaloids","The tricyclic core of the martinellines has been synthesised stereoselectively in two steps, using 1,3-dipolar cycloaddition of azomethine ylides as a key step.",10.1055/s-2002-33922,2002-09-09,0.6048035075239938
Journal of Organic Chemistry,Toward the Synthesis of Norzoanthamine:  Complete Fragment Assembly,"The complex marine alkaloid norzoanthamine (2) was envisioned to be assembled from three key building blocks: the C1-C5 fragment A, the C6-C10 fragment B, and the C11-C24 fragment C. The synthesis of fragment A was achieved in 14 steps and 33% overall yield from (R)-gamma-hydroxymethyl-gamma-butyrolactone. Fragment B was made in two steps from PMB-protected 4-pentynol in 76% yield. The C11-C24 fragment C was made from (S)-carvone via (R)-isocarvone in 18 steps (6% overall yield). The convergent stereoselective synthesis of the entire carbon framework (C1-C24) of the target molecule was achieved via the following assemblage. Alkenyl iodide 20 derived from the C11-C24 fragment C was coupled to fragment B (C6-C10) through a high-yielding Stille coupling reaction of these two sterically very demanding coupling partners, affording the key Diels-Alder precursor 24. The intramolecular Diels-Alder reaction proceeded smoothly in excellent yield and diastereoselectivity, generating the tricyclic trans-anti-trans perhydrophenanthrene motif of norzoanthamine (C6-C24). The final fragment coupling between lithiated fragment A (C1-C5) and aldehyde 40 (C6-C24) has also been successfully accomplished affording the entire carbon framework of the natural product.",10.1021/jo070165r,2007-05-25,0.6048028018737762
Organic Letters,"Transannular <i>O</i>-Heterocyclization: A Useful Tool for the Total Synthesis of Murisolin and 16,19-<i>cis</i>-Murisolin","Transannular O-heterocyclization is applied as a key step in a total synthesis. This highly stereoselective and metal-free transformation introduces four stereocenters in one step. It was chosen to be the pivotal step in the synthesis of Murisolin and 16,19-cis-Murisolin, two annonaceous acetogenins. The efficiency of this synthesis is further illustrated by a stereodivergent late-stage separation of both synthetic routes.",10.1021/ol302820c,2012-11-08,0.6048019962269892
Organic Letters,Scalable Synthesis of Anomerically Pure Orthogonal-Protected GlcN<sub>3</sub> and GalN<sub>3</sub> from <scp>d</scp>-Glucosamine,"An improved and scalable synthesis of orthogonally protected d-glucosamine and d-galactosamine building blocks from inexpensive d-glucosamine has been developed. The key reaction is an inversion/migration step providing access to a fully orthogonal protecting group pattern, which is required for microbial oligosaccharide synthesis. The method can be carried out on a multigram scale as several of the reactions can be purified by crystallization to give anomerically pure products.",10.1021/acs.orglett.6b02241,2016-08-23,0.6048014812393442
Organic Letters,First Enantioselective Total Synthesis of (−)-Centrolobine,[structure: see text] The first enantioselective total synthesis of (-)-Centrolobine is described. The key reaction is the synthesis of the cis-disubstituted tetrahydropyran framework by intramolecular cyclization of the enantiopure hydroxyketone 3 with Et3SiH and TMSOTf. The stereoselective reduction of the beta-ketosulfoxide 4 is the source of chirality. Revision of the absolute configuration of (-)-Centrolobine is proposed.,10.1021/ol025778z,2002-04-17,0.6047986673861259
Angewandte Chemie International Edition,Formal Synthesis of Sarain A: Intramolecular Cycloaddition of an Eight‐Membered Cyclic Nitrone to Construct the 2‐Azabicyclo[3.3.1]nonane Framework,"An enantioselective route to the tetracyclic skeleton of sarain A has been developed. Asymmetric reduction of an ynone introduced a chiral center which was transferred to the contiguous tertiary stereogenic centers through an Ireland-Claisen rearrangement. The 2-azabicyclo[3.3.1]nonane framework was constructed by an unprecedented intramolecular cycloaddition of an eight-membered cyclic nitrone. Using the steric bias of the bicyclic system, the quaternary carbon atom was constructed by a stereoselective aldol reaction. Further ring formations were performed by ring-closing metathesis for the 13-membered ring and an iodoamidation reaction for the pyrrolidine ring. The present synthesis has successfully provided an alternative route to the late-stage intermediate of Overman's synthesis.",10.1002/anie.201501633,2015-05-08,0.6047941978857472
Tetrahedron,Stereoselective synthesis of conjugated all-trans-tetraenes. Application to the synthesis of β-parinaric acid methyl ester,,10.1016/s0040-4039(97)01594-3,1997-09-01,0.604786903015327
Organic Letters,Domino Grignard Addition/Cope–House Reaction for the Synthesis of Polyhydroxylated 3-Methylindolizidines Analogous to Castanospermine,"The first synthesis of polyhydroxylated 3-methylindolizidines is reported. A straightforward domino butenylmagnesium bromide addition/Cope-House reaction to carbohydrate-derived nitrones afforded efficiently the methyl pyrrolidine moiety with good stereoselectivity, which can be reversed by use of Lewis acids. A subsequent one-pot deprotection/deoxygenation/reductive amination step furnished the desired bicyclic architecture, allowing us to afford the desired final products in 3-4 steps from the starting nitrones and 18-30% overall yields.",10.1021/acs.orglett.5c03187,2025-09-02,0.6047818013988278
Organic Letters,Efficient Synthesis of the Tetracyclic Aminoquinone Moiety of Marmycin A,An efficient four-step route to the tetracyclic aminoquinone moiety of marmycin A that proceeds in 41% overall yield from 5-nitronaphthoquinone and 5-methyl-1-vinylcyclohexene will facilitate preparation of marmycin A analogues for biological evaluation. The Diels-Alder reaction gave exclusively the desired adduct that is favored by steric considerations rather than the regioisomeric adduct that is favored by electronic considerations.,10.1021/ol9020496,2009-10-05,0.6047749718038367
Journal of the American Chemical Society,Convergent Total Synthesis of Papililone A via Pd-Catalyzed Alkenylation/Cyclization Cascade,"-inflammatory activity, characterized by its intricate fused-bridged 5/5/5/6 tetracyclic skeleton and six contiguous stereocenters, including two adjacent bridgehead all-carbon quaternary centers, which pose significant challenges to chemical synthesis. Herein we describe the first total synthesis of papililone A in a nine-step longest linear sequence (LLS) from commercial materials without the use of a protecting group, achieved through a cyclization cascade strategy. The strained fused-bridged 5/5/6 tricyclic framework and the two contiguous stereocenters were efficiently constructed in a single step via an unprecedented Pd-catalyzed alkenylation/6-endo-trig cyclization, while the fused 5/5 bicyclic ring system and the vicinal all-carbon quaternary stereocenters were rapidly forged through a combination of a polar-radical cyclization cascade, a convergent fragment coupling, and a vinylogous α-ketol rearrangement in a highly stereoselective manner. This concise approach establishes the β-methyl configuration at C17 as the authentic stereochemistry of naturally occurring papililone A, resolving previous computational ambiguities and facilitating future biological studies.",10.1021/jacs.5c17278,2025-11-28,0.6047563683498943
Organic Letters,Ketyl Radical Cyclization of β-Disubstituted Acrylates: Formal Syntheses of (+)-Secosyrin 1 and Longianone and the Total Synthesis of (+)-4-<i>epi</i>-Secosyrin 1,"A novel approach to the synthesis of a series of 1,7-dioxaspirononanes that applies a ketyl radical cyclization strategy is described. Radical cyclization of the β-disubstituted acrylate 23, prepared in five steps from (R)-1,2-isopropylideneglycerol, gives both 2,3-syn- and 2,3-anti-furan products. The densely functionalized furan heterocycles are used to complete a concise formal synthesis of secosyrin 1, a metabolite of Pseudomonas syringae, and the total synthesis of 4-epi-secosyrin 1.",10.1021/ol4001894,2013-03-01,0.604755752495486
Synthesis,"Direct Syntheses of Tetrathiafulvalene and Bis(ethylenedithio)tetrathiafulvalene By a Non-Coupling Route from 1,4,5,8-Tetrathianaphthalene","All articles of this category 1,3,5,8-Tetrathianaphthalene ( 2 , TTN; 1,4,5,8-tetrathiatetralin) has been synthesized in one step from 4,5-bis(benzoylthio)-1,3-dithiole-2-thione (1) and cis -dichloroethylene in high yield. TTN (2) is readily converted into tetrathiafulvalene ( 2 , TTF) upon tetralithiation or bis(ethylenedithio)tetrathiafulvalene ( 4 , BEDT-TTF) upon tetralithiation, sulfur insertion into the carbon-lithium bond pairs and subsequent capping of the reactive intermediate with 1,2-dibromoethane. The rearrangement of TTN allows for a facile synthesis of TTF and a novel non-coupling route to BEDT-TTF. superconductivity - tetrathianaphthalene - tetrathiafulvalene - bis(ehtylenedithio)tetrathiafulvalene - 13 C-NMR",10.1055/s-1997-1407,1997-06-01,0.6047535264196395
Tetrahedron,Synthesis of both enantiomers of dynemicin A model compound. New remote asymmetric induction in acetylide addition into quinoline nucleus as key step,,10.1016/s0040-4039(00)78406-1,1994-10-10,0.6047346532335356
Tetrahedron,Synthesis of both enantiomers of dynemicin a model compound. New remote asymmetric induction in acetylide addition into quinoline nucleus as key step,,10.1016/0040-4039(94)80032-4,1994-10-01,0.6047346532335356
Synlett,First Total Synthesis of the Benzopyranobenzazepine Alkaloid (±)-Clavizepine,All articles of this category The first total synthesis of (±)-Clavizepine ( 1 ) has been accomplished by using intramolecular aromatic substitutions of the keto ester 8 and the sulfoxide 18 as the key steps.,10.1055/s-1994-22734,1994-01-01,0.604733790714479
Journal of Organic Chemistry,Synthetic Approaches and Total Synthesis of Natural Zoapatanol,[structure: see text] The total synthesis of (+)-zoapatanol utilizing an intramolecular Horner-Wadsworth-Emmons olefination and an enantioselective Sharpless dihydroxylation as the key steps has been achieved. An advanced oxepene intermediate has been obtained by applying a ring-closing metathesis to an unsaturated enol ether.,10.1021/jo048115z,2005-02-12,0.6047299012418846
Tetrahedron,"A new, simple, efficient synthesis of benzo[b]carbazoles and indeno[1,2-b]indoles",,10.1016/0040-4039(93)85075-8,1993-10-01,0.6047277366352507
Angewandte Chemie International Edition,A Concise and Versatile Synthesis of Alkaloids from <i>Kopsia tenuis</i>: Total Synthesis of (±)‐Lundurine A and B,"A total synthesis of (±)-lundurines A and B is described. These natural products have a unique hexacyclic skeleton which includes a cyclopropane-fused indoline. A stereospecific construction of the pentasubstituted cyclopropane core was achieved, by radical cyclization using SmI2, with perfect stereoselectivity. Cyclizations to give seven- and five-membered heterocycles, under palladium and ruthenium catalysis, respectively, accomplished the total syntheses. The late-stage construction of the F ring by ring-closing metathesis enabled access to the title compounds from a spiroindoline intermediate which is a common structure of other kopsia alkaloids.",10.1002/anie.201400464,2014-05-25,0.6047141349434734
Journal of Organic Chemistry,"Synthesis of Spirovetivane Sesquiterpenes from Santonin. Synthesis of (+)-Anhydro-β-rotunol and All Diastereomers of 6,11-Spirovetivadiene","The synthesis of the spirovetivane sesquiterpenes (+)-anhydro-beta-rotunol and all the diastereomers of 6,11-spirovetivadiene in enantiomerically pure form has been achieved starting from santonin. The key step is the silicon-guided acid-promoted rearrangement of a 1-trimethylsilyl-4,5-epoxyeudesmane prepared from santonin in several steps involving lactone reductive opening, conjugate addition of TMSLi-CuCN, deoxygenation of a carbonyl group, and epoxidation. Rearrangement of the epoxide gave a spiro[4,5]decanediol which was used as a synthetic intermediate. From this compound, (+)-anhydro-beta-rotunol was prepared after elimination of the primary hydroxyl group in the side chain, followed by allylic oxidation at C8 and elimination of the tertiary hydroxyl group in the cyclohexane ring. On the other hand, elimination of the hydroxyl group in the side chain and reduction of the hydroxyl in the cyclohexane ring gave (-)-premnaspirodiene and (-)-hinesene. The synthesis of the rest of the diastereomers for these compounds required formal inversion of the C5 spiro carbon. The synthesis of these compounds showed that the structure of (-)-agarospirene isolated from Scapania sp. was erroneously assigned, and it has been corrected to be identical to that of (-)-hinesene.",10.1021/jo040189n,2004-09-23,0.6047079356747536
Journal of Organic Chemistry,"Synthesis of a Pentasaccharide Fragment of Varianose, a Cell Wall Polysaccharide from <i>Penicillium varians</i>","The first synthesis of an oligosaccharide fragment of varianose, a polysaccharide produced by Penicillium varians, is reported. The target pentasaccharide features both alpha- and beta-galactofuranoside residues and the alpha-galactofuranoside residue is hindered, being substituted on adjacent oxygens (O1 and O2), both of which are cis to the two-carbon side chain at C4. Key features of the synthesis include a novel method for the selective protection of the C3 hydroxyl group of galactofuranosyl residues via an epoxide formation/opening sequence, the introduction of the alpha-d-galactofuranosyl residue using a 2,3-anhydrosugar donor, and the use of the 1-benzenesulfinylpiperidine/trifluoromethanesulfonic anhydride activation method for the addition of an alpha-D-glucopyranosyl residue to a hindered hydroxyl group in an advanced tetrasaccharide intermediate.",10.1021/jo061821a,2006-11-23,0.6047034664078785
Organic Letters,Stereoselective Route to Oxetanocin Carbocyclic Analogues Based on a [2 + 2] Photocycloaddition to a Chiral 2(5<i>H</i>)-Furanone,"The synthesis of the trisubstituted cyclobutane 7, which is a suitable precursor for the preparation of oxetanocin carbocyclic analogues, is described. The key step involves a regio- and diastereoselective [2 + 2] photochemical reaction of ketene diethyl acetal with (S)-5-pivaloyloxymethyl-2(5H)-furanone, 3. As an application of this methodology, (-)-cyclobut-A has been prepared from the intermediate 7.",10.1021/ol0710616,2007-06-21,0.6047009611713675
European Journal of Organic Chemistry,"Synthesis of Acerogenin C and (+)-Acerogenin A, Two Macrocyclic Diarylheptanoid Constituents ofAcer nikoense","The macrocyclic ketone acerogenin C (3) and the corresponding alcohol (+)-accerogenin A (1), diarylheptanoid constituents of the maple Acer nikoense were synthesized. The key steps were the selective reduction of the double bond of an α,β-unsaturated ketone (10) and macrocyclization of an iodophenol (13) by a modified Ullmann diarylether synthesis.",10.1002/(sici)1099-0690(199803)1998:3<521::aid-ejoc521>3.0.co;2-i,1998-03-01,0.6046992495355098
European Journal of Organic Chemistry,An Efficient Enantioselective Synthesis of Strigolactones with a Palladium-Catalyzed Asymmetric Coupling as the Key Step,"An efficient enantioselective methodology for the preparation of the strigolactones GR7, GR24 and Nijmegen-1 based on palladium-catalyzed asymmetric coupling has been developed. The products are obtained in good yield and high optical purity. This methodology is an attractive alternative for installing the stereochemistry at C2′ of the D-ring. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)",10.1002/1099-0690(200203)2002:5<810::aid-ejoc810>3.0.co;2-u,2002-03-01,0.6046912909319867
Angewandte Chemie International Edition,"A General Strategy for Construction of Both 2,6‐<i>cis</i>‐ and 2,6‐<i>trans</i>‐Disubstituted Tetrahydropyrans: Substrate‐Controlled Asymmetric Total Synthesis of (+)‐Scanlonenyne","A synthetic three-ring circus: The asymmetric total synthesis of (+)-scanlonenyne includes a sequential epimerization and intramolecular hetero-Michael addition for the construction of pyrano-γ-lactones (see scheme; DBU: 1,8-diazabicyclo[5.4.0]undec-7-ene), a highly efficient one-carbon homologation/bromination strategy, and a Weinreb ketone synthesis/cross-metathesis protocol for the elaboration of a sensitive side chain.",10.1002/anie.200705663,2008-04-25,0.6046753620709181
Organic Process Research & Development,"Efficient and Practical Synthesis of 3′,4′,5′-Trifluoro-[1,1′-biphenyl]-2-amine: A Key Intermediate of Fluxapyroxad","An improved and practical method is reported here for accessing 3′,4′,5′-trifluoro-[1,1′-biphenyl]-2-amine ( 1 ), a key intermediate for Fluxapyroxad. The overall yield for the preparation of 1 was 73%, with a purity of 99.88%, after a three-step process. More importantly, this process was an improvement in the manufacture of biphenyl compounds by Suzuki–Miyaura coupling, which enabled catalyst loading as low as 0.04 mol %. This method could provide an economic and environment-friendly process leading to extensive prospects in industrial applications.",10.1021/acs.oprd.9b00208,2019-08-14,0.6046649088111835
Organic Process Research & Development,"Research and Development of an Efficient Synthesis of Hexahydrofuro[2,3-<i>b</i>]furan-3-ol Moiety—A Key Component of the HIV Protease Inhibitor Candidates","A highly efficient method for synthesizing racemic hexahydrofuro[2,3- b ]furan-3-ol has been developed utilizing a lanthanide catalyst, such as Yb(fod) 3, to promote condensation of 2,3-dihydrofuran and glycolaldehyde dimer. Access to either optically enriched enantiomer of bisfuran alcohol can be obtained by using this method employing chiral ligands with the lanthanide catalyst. In support of Gilead Sciences’ protease inhibitor project, this method has been demonstrated to be a robust and scalable process with potential application for the construction of a variety of furo[2,3- b ]furan derivatives.",10.1021/op700160a,2007-10-05,0.6046544324903161
Organic Letters,A Stereoselective Approach toward (−)-Lepadins A–C,"A new short approach to (-)-lepadins A-C has been developed based on a stereocontrolled Diels-Alder reaction employing a chiral dienophile. With this approach, (-)-lepadin B is synthesized from 5-deoxy-d-ribose in 13 steps with 14.8% overall yield. The cis-decahydroquinoline core containing five stereocenters could be rapidly constructed via stereoselective cycloaddition and subsequent five-step one-pot hydrogenation-cyclization.",10.1021/acs.orglett.7b02647,2017-09-19,0.6046534948041564
Journal of Organic Chemistry,"An Improved Synthesis of (4 <i>S</i> ,5 <i>S</i> )-2-Phenyl-4-(methoxycarbonyl)-5- isopropyloxazoline from ( <i>S</i> )-Phenylglycinol",,10.1021/jo972013+,1998-03-17,0.6046375168148903
Tetrahedron,"A novel route to 6-substituted and 5,6-disubstituted 2-pyrones",,10.1016/s0040-4039(01)00290-8,2001-04-01,0.6046358885659511
Tetrahedron,"Synthesis and stereochemical confirmation of the HI/JK ring system of prymnesins, potent hemolytic and ichthyotoxic glycoside toxins isolated from the red tide alga",,10.1016/s0040-4039(01)01067-x,2001-08-01,0.6046339117801391
Tetrahedron,Synthesis of amorfrutins B and D from amorfrutin A ethyl ester,,10.1016/j.tetlet.2019.151477,2019-12-05,0.6046270105499028
Journal of Organic Chemistry,"Total Synthesis of α-1<i>C</i>-Galactosylceramide, an Immunostimulatory <i>C</i>-Glycosphingolipid, and Confirmation of the Stereochemistry in the First-Generation Synthesis","A nonisosteric α-C-glycoside analogue of KRN7000 (α-1C-GalCer, 1) was reported to induce a selective type of cytokine release in human invariant natural killer cells in vitro. We report here a very concise synthetic route to 1 and its analogue 1'. The key steps include olefin cross-metathesis, Sharpless asymmetric epoxidation, and epoxide opening by NaN(3)/NH(4)Cl. Inversion of configuration at the amide-bearing carbon in the phytosphingosine backbone constructed by epoxide opening in our previous synthesis of 1 was verified, indicating that remote group participation is not involved during the epoxide-opening reaction.",10.1021/jo201450s,2011-09-28,0.6046210304946089
Journal of Organic Chemistry,"Photoassisted Diversity-Oriented Synthesis: Accessing 2,6-Epoxyazocane (Oxamorphan) Cores","The modular synthesis of photoprecursors and their photoinduced cyclization into substituted 1-benzazocanes of two distinct topologies is described. The key step producing an extended polyheterocyclic system involves the photogeneration of azaxylylenes and their subsequent intramolecular cycloaddition with furan-containing pendants tethered either via the aniline nitrogen or through the carbonyl group containing arm. The primary photoproducts-secondary or tertiary anilines which are not acylated at the nitrogen atom-undergo facile acid-catalyzed or spontaneous ring-opening-ring-closing rearrangement to yield fused polyheterocyclic structures possessing a 2,6-epoxyazocane (or oxamorphan) core.",10.1021/jo5019848,2014-11-05,0.6046169375135044
Journal of the American Chemical Society,Dyotropic Rearrangements of Fused Tricyclic β-Lactones: Application to the Synthesis of (−)-Curcumanolide A and (−)-Curcumalactone,"Dyotropic rearrangements of fused, tricyclic β-lactones are described that proceed via unprecedented stereospecific, 1,2-acyl migrations delivering bridged, spiro-γ-butyrolactones. A unique example of this dyotropic process involves a fused bis-lactone possessing both β- and δ-lactone moieties which enabled rapid access to the core structures of curcumanolide A and curcumalactone. Our current mechanistic understanding of the latter dyotropic process, based on computational studies, is also described. Other key transformations in the described divergent syntheses of (-)-curcumanolide A and (-)-curcumalactone from a common intermediate (11 and 12 steps from 2-methyl-1,3-cyclopentanedione, respectively), include a catalytic, asymmetric nucleophile (Lewis base)-catalyzed aldol-lactonization (NCAL) leading to a tricyclic β-lactone, a Baeyer-Villiger oxidation in the presence of a β-lactone, and highly facial-selective and stereocomplementary reductions of an intermediate spirocyclic enoate. The described dyotropic rearrangements significantly alter the topology of the starting tricyclic β-lactone, providing access to complex spirocyclic cyclopentyl-γ-lactones and bis-γ-lactones in a single synthetic operation.",10.1021/ja303414a,2012-08-01,0.604609542766149
European Journal of Organic Chemistry,Synthesis of a Cyclic Tetrameric Purine by Successive Cross‐Coupling Reactions and Subsequent Pd‐Catalyzed Cyclization,"Abstract The tetrameric N ‐benzyl‐protected purine (quaterpurine) 2 was synthesized and characterized as its palladium complex [ 2· Pd]. The synthesis commenced with the Pd‐catalyzed cross‐coupling of 8‐ z incated 9‐benzyl‐6‐chloro‐8‐iodopurine ( 9 ) and 9‐benzyl‐6‐iodopurine ( 11 ) establishing the first C‐6/C‐8 bond. The sequence was repeated twice after iodo‐de‐chlorination at C‐6′ (C‐6″) of the respective dimer 12 and trimer 15 . The final ring closure was achieved at the tetrameric 6″′‐chloro‐8‐iodoquaterpurine 3b by a reductive intramolecular cross‐coupling with hexamethylditin in the presence of Pd 2 (dba) 3 and P(2‐furyl) 3 . The overall yield in the eight step sequence was 17 % starting from 9‐benzyl‐6‐chloropurine ( 8 ), the immediate precursor of 11 . Other strategies to combine the purine fragments, i.e. by dimer/dimer bond formation or by regioselective cross‐coupling, were not successful. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2007)",10.1002/ejoc.200600724,2006-11-29,0.6046073333772863
Organic Letters,"A Modified Approach to 2-(<i>N</i>-Aryl)-1,3-oxazoles:  Application to the Synthesis of the IMPDH Inhibitor BMS-337197 and Analogues","[structure: see text] A modified approach to the synthesis of 2-(N-aryl)-1,3-oxazoles, employing an optimized iminophosphorane/heterocumulene-mediated methodology, and its application to the synthesis of BMS-337197, a potent inhibitor of IMPDH, are described.",10.1021/ol020073i,2002-05-22,0.6045972333143405
Synlett,Total Synthesis of Largazoleand Its Biological Evaluation,"We achieved a total synthesis of largazole. The optically active β-hydroxycarbonyl unit was prepared from a modified Nagao's N-acetylthiazolidinethione. A 4-methylthiazoline-thiazole amino ester was prepared by both a step-by-step method and tandem cyclization from Cys-2-MeCys-containing tripeptide. Amidation of the activated β-hydroxycarbonyl unit and 4-methyl-thiazoline-thiazole-containing amino ester, followed by esterification with N-Fmoc valine afforded cyclization precursor after selective removal of the methyl ester at the C-terminus and the Fmoc group at the N-terminus. Macrolactamization, deprotection of thiol, and S-acylation provided largazole. Biological evaluation of its S-modified derivatives as well as the synthetic largazole exhibited strong inhibitory activity against histone deacetylases (HDAC).",10.1055/s-2008-1078263,2008-08-22,0.6045921997446527
Organic Letters,Construction of Multifunctional Modules for Drug Discovery: Synthesis of Novel Thia/Oxa-Azaspiro[3.4]octanes,"New classes of thia/oxa-azaspiro[3.4]octanes are synthesized through the implementation of robust and step-economic routes. The targeted spirocycles have been designed to act as novel, multifunctional, and structurally diverse modules for drug discovery. Furthermore, enantioselective approaches to the spirocycles are reported.",10.1021/ol402127b,2013-08-30,0.6045856625065894
Journal of Organic Chemistry,Catalytic Enantioselective Approach to the Stereodivergent Synthesis of (+)-Lasubines I and II,"A concise and efficient approach to the stereodivergent synthesis of (+)-lasubines I and II is described. The key common intermediate is a chiral N-sulfonyl 2,3-dihydropyridone obtained by a novel Cu-catalyzed asymmetric formal aza-Diels-Alder reaction between N-tosyl aldimines and Danishefsky's diene.",10.1021/jo702076j,2007-11-21,0.6045802942156127
Organic Letters,Scalable Synthesis of an Acid Stable Analogue of Hippuristanol,"Hippuristanol is a marine derived steroidal natural product with promising anticancer activity. However, instability at low pH has precluded its development as an efficient therapy. We addressed this limitation by replacing one of the oxygen atoms of the spiroketal moiety with a carbon atom. Key steps in the synthesis include a Meyer-Schuster/Nazarov cascade, a hypoiodite mediated oxyfunctionalization, and the late-stage installation of a hydroxyl group on the C-ring of the steroid.",10.1021/acs.orglett.4c02615,2024-08-09,0.6045749652558662
Organic Letters,Asymmetric Total Synthesis of <i>ent</i>-Cyclooroidin,"An enantiospecific total synthesis of the pyrrole-imidazole natural product cyclooroidin from histidine is described. The key N1-C9 bond is constructed through an intramolecular SN2-type of reaction of a chloro ester. Subsequent imidazole azidation at the 2-position, pyrrole bromination, azide reduction, and deprotection leads to the completion of the synthesis.",10.1021/ol1020916,2010-10-07,0.6045744105385088
Journal of Organic Chemistry,Enantioselective Synthesis of Pyrrolizin-1-ones via Lewis Base Catalyzed N-Allylation of <i>N</i>-Silyl Pyrrole Latent Nucleophiles,"Pyrrolizidine alkaloids and their derivatives often feature interesting biological activities. A class of substituted 2,3-dihydro-1 H -pyrrolizin-1-one derivatives has been explored as a potential treatment for Alzheimer’s disease, but enantioselective synthesis of these molecules is still elusive. We report that enantioselective N-allylation of N -silyl pyrrole latent nucleophiles with allylic fluorides followed by hydrogenation and diastereoselective Friedel–Crafts cyclization constitute an efficient synthetic route to access enantioenriched substituted 2,3-dihydro-1 H -pyrrolizin-1-ones.",10.1021/acs.joc.9b02819,2019-12-05,0.6045727746568089
Organic Letters,Enantioselective Total Synthesis of Cyathin A<sub>3</sub>,"The total synthesis of (-)-cyathin A3 is described. The key step involves an unusual enantioselective Diels-Alder reaction of 2,5-dimethyl-1,4-benzoquinone with 2,4-bis(trimethylsilyloxy)-1,3-pentadiene, using Mikami's catalyst [(R)-BINOL + Cl2Ti(OiPr)2 + 4 A mol sieves] modified by addition of Mg and SiO2. Because cyathin A3 is easily transformed into allocyathin B3, cyathin B3, cyathin C3, and neoallocyathin A4, this route also constitutes formal syntheses of these natural products.",10.1021/ol070994z,2007-06-20,0.6045675795590855
Tetrahedron,Methyl 3-phenylsulphonyl orthopropionate: an efficient reagent for the synthesis of γ-lactones and butenolides,,10.1016/s0040-4039(00)96063-5,1987-01-01,0.6045595666185878
Organic Letters,Accessing Highly Oxidized Imidazolidinone Cores via a Curtius Rearrangement: Total Synthesis of Colensolide A,The hydroxytetrahydropyrrolo-imidazolidinone (HTHP-I) core present in colensolide A is a synthetically intriguing scaffold as a result of its high heteroatom/carbon ratio and perceived instability. The similarity of this core to other potent biological scaffolds has led us to develop a synthetic route utilizing isocyanate chemistry to access this core and complete the first total synthesis of colensolide A.,10.1021/acs.orglett.3c01139,2023-05-15,0.6045545414533104
Journal of Organic Chemistry,Total Synthesis of Dermostatin A,"The concise total synthesis of dermostatin A is described. Highlights include a two-directional application of the asymmetric acetate aldol method developed in our lab, a novel diastereotopic-group-selective acetal isomerization for terminus differentiation, and a selective cross-metathesis reaction between a terminal olefin and a trienal. A study of the scope and viability of similar cross-metathesis reactions is also described. The synthesis is convergent and utilizes fragments of roughly equal complexity.",10.1021/jo2012658,2011-08-10,0.6045498405994609
Synlett,Studies toward the Total Synthesis of Sorangicins: Asymmetric Synthesis of the Key Fragments,"Efficient synthesis of the key fragments of the complex antibiotics class of sorangicins (Scheme [1] ) is described. Starting from simple compounds fragments I, II, and IV can be synthesized. For fragment III we chose an approach via l-glucal.",10.1055/s-2004-835661,2004-11-10,0.6045407279603364
Organic Letters,SmI<sub>2</sub>-Mediated Couplings of α-Amino Acid Derivatives. Formal Synthesis of (−)-Pumiliotoxin 251D and (±)-Epiquinamide,"The coupling between cyclic and acyclic α-amino acid derivatives and methyl acrylate, mediated by samarium diiodide, is described. The method constitutes a powerful tool to construct indolizidine, quinolizidine, and piperidine systems in a straightforward two-step fashion. The formal synthesis of (-)-pumiliotoxin 251D and (±)-epiquinamide is achieved after two or three steps from these amino acid derivatives.",10.1021/ol400903n,2013-05-02,0.604514051069737
Organic Letters,Convergent Formal Syntheses of (±)-Brussonol and (±)-Abrotanone via an Intramolecular Marson-Type Cyclization,The formal convergent syntheses of both (+/-)-brussonol and (+/-)-abrotanone are reported. The key step involved the diastereoselective capture of an in situ generated oxocarbenium cation via an intramolecular Friedel-Crafts/Marson-type cyclization.,10.1021/ol802375g,2008-12-03,0.6045133559173831
Organic Letters,A Stereocontrolled Synthesis of δ-<i>trans</i>-Tocotrienoloic Acid,"[reaction: see text] A concise stereoselective total synthesis of a naturally occurring polymerase beta inhibitor, delta-trans-tocotrienoloic acid (2), is described. The key step in the synthesis is an acid-catalyzed cyclodehydration reaction. Additionally, this report corrects a previously reported structural assignment, defines the absolute stereochemistry of 2, and defines key structural requirements for polymerase beta inhibition.",10.1021/ol051849t,2005-08-20,0.6045094898020861
Synlett,Versatile Oxabicyclic Synthons: Studies on C8-Oxygenated Eunicellin Diterpenes,"In this letter, we describe the first approach to the synthesis of C8-oxygenated eunicellin diterpenes starting with a highly functionalized 8-oxabicyclo[3.2.1]octadiene system. The route features two sequential annulations to append a six- and five-membered ring onto the core structure followed by oxidative cleavage to reveal the eunicellin skeleton. Key to this strategy is a diastereo­selective intramolecular Nozaki-Hiyama-Kishi (NHK) closure to establish the correct relative stereochemical relationship at C6 and C8 of the natural product.",10.1055/s-2007-986667,2007-09-12,0.6045048389173685
Synthesis,Stereoselective Synthetic Routes to Iminosugars: A Divergent Approach Utilizing a Common Multifunctional Chiral Scaffold,"Abstract Starting from an l-serine-derived multifunctional aminobutenolide as a common chiral building block, stereoselective synthetic routes to representative examples of di-, tri-, and tetrahydroxylated iminosugars have been developed. Key steps in the synthetic routes involved an intramolecular aminolysis protocol to form the azaheterocyclic core, and functionalization of a resident alkene moiety towards installation of the desired substituents at the various positions of the piperidine ring. The strategy and the approach described are expected to provide flexible synthetic routes to various iminosugar scaffolds of structural and medicinal chemical significance.",10.1055/a-2353-1618,2024-06-26,0.6045028562492847
Journal of Organic Chemistry,Concise and Efficient Synthesis of 2-Acetamido-2-deoxy-β-<scp>d</scp>-hexopyranosides of Diverse Aminosugars from 2-Acetamido-2-deoxy-β-<scp>d</scp>-glucose,"The furanose acetonide derivative 1 is readily prepared from 2-acetamido-2-deoxy-D-glucose on a large scale without the need for chromatography. Mesylation of 1 provides an efficient, concise, synthetic route to rare 2-acetamido-2-deoxy-beta-D-hexopyranosides (2 and 3) via the corresponding methyl 2-acetamido-2-deoxy-3-O-methanesulfonyl-beta-D-glucopyranoside and subsequent inversion of configuration by direct displacement or formation of a 3,4-epoxide. Opening of this epoxide by azide provided a direct route to methyl 2-acetamido-4-amino-2,4,6-trideoxy-beta-D-gulopyranoside 4. Benzylation of 1 followed by ring expansion to the glucopyranoside, deoxygenation at C-6, and subsequent displacement of a C-4 triflate permitted the synthesis of methyl 2-acetamido-4-amino-2,4,6-trideoxy-beta-D-galactopyranoside 5. Methyl 2-acetamido-2-deoxy-beta-D-glucopyranoside available from 1 in quantitative yield was readily converted to methyl 2-acetamido-2-deoxy-beta-D-galactopyranoside 6 (>60%) by inversion of configuration at C-4. Introduction of a lactyl substituent at C-3 of oxazoline 1 also provides a facile synthesis of the biologically important muramic acid beta-glycoside 7. An interesting reaction to convert 2-acetamido-2-deoxyhexopyranosides to the corresponding 2-deoxy-2-tetrazole is also reported.",10.1021/jo801927k,2008-12-08,0.604498563496836
Journal of Organic Chemistry,Total Synthesis of (−)-Cinatrin C<sub>1</sub> Based on an In(OTf)<sub>3</sub>-Catalyzed Conia-Ene Reaction,"The stereocontrolled total synthesis of (-)-cinatrin C1, a phospholipase A2 inhibitor, has been accomplished. The key feature includes the stereoselective construction of the highly substituted tetrahydrofuran core by In(OTf)3-catalyzed Conia-ene reaction of the oxygen-tethered acetylenic malonic ester followed by dihydroxylation with concomitant lactonization.",10.1021/jo400263w,2013-04-02,0.6044955645643758
Organic Letters,Collective Biomimetic Synthesis of Myrcaulones A and C and Myrcauones B–D,"We report the first collective biomimetic synthesis of noncanonical phloroglucinol derivatives myrcaulones A ( 1 ) and C ( 3 ), featuring a unique ring-contracted phloroglucinol skeleton, along with three biosynthetically related canonical phloroglucinol derivatives myrcauones B–D ( 4 – 6 ). These compounds were synthesized in only 6–9 steps, starting from the commercially available 3,4,5-trimethoxyphenol. Key features of the synthetic strategy include a hetero -Diels–Alder reaction to construct the canonical phloroglucinol framework and an α-ketol rearrangement-driven ring contraction reaction to form the noncanonical phloroglucinol skeleton.",10.1021/acs.orglett.5c01758,2025-06-06,0.6044916224244526
Angewandte Chemie International Edition,Formal Total Synthesis of Platencin,"The right bicycle: A concise formal synthesis of platencin was based on an efficient oxygen-mediated palladium-catalyzed cycloalkenylation of 1 to form a bicyclo[3.2.1]octane, and a deoxygenative rearrangement of tosylhydrazone 2 to construct the bicyclo[2.2.2]octane 3. The total yield of the core structure 4 of platencin was 17.5% for 13 steps from a commercially available compound. Ts = p-toluenesulfonyl, TBS = tert-butyldimethylsilyl, Piv = pivaloyl.",10.1002/anie.200900447,2009-04-07,0.6044797470238975
Journal of Organic Chemistry,A Simple and Versatile Route to Novel Conjugated <i>β</i>-Enaminonitriles and Their Application for the Highly Regioselective Synthesis of Nicotinonitriles Using a Vilsmeier-Type Reagent,A straightforward synthesis of conjugated β -enaminonitriles from ketones and β -aminocrotononitrile mediated by TiCl 4 is described. The reaction of these novel dienamines with a Vilsmeier-type reagent provides a mild and highly regioselective route for the preparation of nicotinonitriles.,10.1021/jo990313g,1999-07-09,0.6044758541176157
Journal of the American Chemical Society,True and false chirality and absolute asymmetric synthesis,No abstract available.,10.1021/ja00278a029,1986-09-01,0.6044690721149648
Synthesis,Improved Synthesis of Bis(ethylenedithio)tetrathiafulvalene (BEDT-TTF): π-Donor for Synthetic Metals,"All articles of this category 2,5,7,9-Tetrathiabicyclo[4.3.0)]non-1(6)-en-8-thione ( 3 ) is prepared in increased yield by isolating the intermediate 4,5-dimercapto-1,3-dithiole-2-thione disodium salt ( 2 ) which undergoes efficient ring-closure with 1,2-dibromoethane. Quantitative oxidation of 3 with mercuric acetate to 2,5,7,9-tetrathiabicyclo [4.3.0]non-1(6)-en-8-one ( 4 ) followed by coupling with triethyl phosphite yields bis(ethylenedithio) tetrathiafulvalene (BEDT-TTF) in high overall yield.",10.1055/s-1987-28095,1987-01-01,0.604467390537168
European Journal of Organic Chemistry,"Stereoselective Synthesis of <i>cis</i>‐2,6‐Disubstituted Morpholines and 1,4‐Oxathianes by Intramolecular Reductive Etherification of 1,5‐Diketones","Abstract A simple and efficient, Lewis acid catalysed reductive etherification strategy for the stereoselective synthesis of cis ‐2,6‐disubstituted morpholines and 1,4‐oxathianes starting from readily available 1,5‐diketones has been developed. The strategy is used in the total synthesis of morpholine‐based natural products (±)‐chelonin A and formal total synthesis of (±)‐chelonin C.",10.1002/ejoc.201403294,2014-11-26,0.6044553499356248
Journal of Organic Chemistry,"Evolution of a Unified, Stereodivergent Approach to the Synthesis of Communesin F and Perophoramidine","Expedient synthetic approaches to the highly functionalized polycyclic alkaloids communesin F and perophoramidine are described using a unified approach featuring a key decarboxylative allylic alkylation to access a crucial and highly congested 3,3-disubstituted oxindole. Described are two distinct, stereoselective alkylations that produce structures in divergent diastereomeric series possessing the critical vicinal all-carbon quaternary centers needed for each synthesis. Synthetic studies toward these challenging core structures have revealed a number of unanticipated modes of reactivity inherent to these complex alkaloid scaffolds. Additionally, several novel and interesting intermediates en route to the target natural products, such as an intriguing propellane hexacyclic oxindole encountered in the communesin F sequence, are disclosed. Indeed, such unanticipated structures may prove to be convenient strategic intermediates in future syntheses.",10.1021/jo502534g,2014-11-17,0.6044547096130041
Angewandte Chemie International Edition,Stereoselective Total Synthsis of (±)‐Urechitol A,"I want to ride my tricycle: Urechitol A was synthesized as a racemate by using a [4+3] cycloaddition reaction and methanol assisted intramolecular epoxide opening as the key steps for the efficient construction of the core tricyclic framework. The overall yield was 2.3 % over 12 steps. Bn=benzyl, TES=triethylsilyl.",10.1002/anie.201002505,2010-07-06,0.6044420193869714
Tetrahedron,"New and efficient RCM in pyridinic series: synthesis of 2H-dihydropyrano- or 2,3H-dihydrooxepino[3,2-b]pyridines",,10.1016/j.tetlet.2006.06.139,2006-07-21,0.6044373834560635
Journal of the American Chemical Society,Enantioselective Total Synthesis of Batzelladine F and Definition of Its Structure,"Batzelladine F (1) was synthesized in enantioselective and stereoselective fashion in 15 steps (longest linear sequence) and 1.7% overall yield from two readily available enantioenriched beta-hydroxy esters, methyl (R)-3-hydroxydecanoate and methyl (R)-3-hydroxybutyrate. Tethered Biginelli condensations are used to assemble both tricyclic guanidine fragments, with the second tethered Biginelli condensation (14 + 16 --> 17) also being employed to join the guanidine fragments. Three diastereomers of batzelladine F, 2-4, were prepared also. A combination of HPLC, optical rotation and CD spectroscopy was employed to distinguish stereoisomers 1-4, proving that 1 is the correct structure of the hexacyclic marine alkaloid batzelladine F.",10.1021/ja057433s,2006-02-02,0.6044348313047038
Journal of the American Chemical Society,Structural Elucidation and Bioinspired Total Syntheses of Ascorbylated Diterpenoid Hongkonoids A–D,"Hongkonoids A-D (1-4), the first example of ascorbylated terpenoids featuring a unique 5,5,5-fused tricyclic spiroketal butyrolactone moiety and diterpenoid-derived long chain, were isolated from Dysoxylum hongkongense. Their structures were unambiguously assigned by a combination of spectroscopic data, chemical degradation, X-ray crystallography, CD analysis, and total synthesis. The total syntheses of compounds 1-4 were effectively accomplished by a convergent strategy with the longest linear sequences of 12-14 steps and overall yields of 5.4-9.6%. Notably, we exploited a bioinspired one-pot method to construct the key intermediate 14 from an easily made compound 12 by involving the cascade reactions of an elaborate Claisen rearrangement, deprotections, and a 5-exo-trig cyclization. The desired major epimer 14a was then transformed to the main building block 21. Assembly of 21 and the long chain vinyl iodide 7 was made by an NHK coupling reaction to furnish the framework of 1-4. Some of the hongkonoids and/or synthetic analogs showed significant to moderate inhibitory activities against NF-κB, 11β-HSD1, and sterol synthesis. The most active NF-κB inhibitor 34 exhibited distinct inhibition on the LPS-induced inflammatory responses in RAW 246.7 and primary BMDM cells.",10.1021/jacs.7b10135,2018-02-02,0.6044322309642839
Journal of Organic Chemistry,Stereoselective Approach to <i>C</i>-Aryl Pyranoside Synthesis Which Addresses the Problem of C7-Substitution in Blepharocalyxin E,"A general route to a series of aryl-substituted pyranoside derivatives has been developed as a model for the synthesis of blepharocalyxin E. Two exo-substituted tetrahydro-4H-furo[2,3-b]pyran-2-one derivatives, 8a and 8b, were prepared and treated separately with anisole and phenoxytriisopropylsilane under Lewis acid conditions to effect C-aryl pyranoside synthesis. In each case, a gamma-lactone was formed, which rearranged to the desired structure on acid treatment. Four compounds (12, 14, 16, and 18) were prepared by this route as single isomers in good overall yield.",10.1021/jo0355909,2004-02-20,0.6044294176625394
Journal of Organic Chemistry,Enantioselective Synthesis of (+)-Isobretonin A,"An enantioselective synthesis of (+)-isobretonin A is described. The chiral glycerol moiety was enantioselectively prepared by reduction of an optically active beta-keto sulfoxide. The all-trans trienic part of the molecule was stereoselectively synthesized via reductive elimination of a 1,6-dibenzoate 2,4-diene with sodium amalgam.",10.1021/jo960134o,1996-01-01,0.6044292156898164
Tetrahedron,"(4S,5S)-4-Benzylamino-5-[((tert-butyl)diphenylsilyl)oxymethyl]-dihydro-2(3H)-furanone. A new intermediate for the enantiospecific synthesis of β-aminoesters and β-lactams",,10.1016/0040-4039(95)01417-g,1995-09-01,0.6044225120580958
Tetrahedron,Enantioselective synthesis of 2-[(3-ethyl-4-piperidyl)methyl]indoles from a phenylglycinol-derived lactam: formal synthesis of Strychnos alkaloids,,10.1016/j.tetlet.2007.07.079,2007-07-22,0.604418526578281
Chemical Science,A modular approach to prepare enantioenriched cyclobutanes: synthesis of (+)-rumphellaone A,A modular synthesis of enantioenriched polyfunctionalized cyclobutanes was developed that features an 8-aminoquinolinamide directed C-H arylation reaction. The C-H arylation products were derivatized through subsequent decarboxylative coupling processes. This synthetic strategy enabled a 9-step enantioselective total synthesis of the antiproliferative meroterpenoid (+)-rumphellaone A.,10.1039/c8sc05444d,2018-12-19,0.6044120950878754
Synthesis,A One-Step Synthesis of Thiophene Derivatives,,10.1055/s-1982-30063,1982-01-01,0.6044047078242227
Tetrahedron,"A five step synthesis of (d,l)-estrane derivatives from 1,3-butadiene",,10.1016/s0040-4039(00)91966-x,1993-03-01,0.6044047078242227
Synlett,An Efficient Synthesis of the Pentasaccharide Repeating Unit of Pseudomonas aeruginosa Psl Exopolysaccharide,"Pseudomonas aeruginosa is a biofilm-forming Gram-negative bacterium and a leading cause of life-threatening nosocomial infections. The polysaccharide synthesis locus (Psl) exopolysaccharide of P. aeruginosa is a key constituent of the defending bacterial biofilm layer and is a promising therapeutic target for resistant species. The Psl exopolysaccharide is built up from repeating pentasaccharide units which contain one α- and two β-mannosidic linkages, and one l-rhamnose and one d-glucose moieties. The preparation of this pentasaccharide was first described by Boons et al. in a 34-step synthesis. Based on their work, we have developed a new and effective pathway for the synthesis of the repeating pentasaccharide unit of the Psl exopolysaccharide. We have succeeded in simplifying the synthesis of the l-rhamnose and the α-selective d-mannose building blocks. Furthermore, taking advantage of a chemoselective pre-activation-based β-mannosylation, we directly prepare a thioglycoside disaccharide donor and use it in the next coupling reaction without further transformation. The pentasaccharide, in the form of a p-methoxyphenyl glycoside, is prepared in 26 steps, which is suitable for biological testing.",10.1055/s-0039-1690747,2019-11-19,0.6044031769342234
European Journal of Organic Chemistry,A Constrained Diketopiperazine as a New Scaffold for the Synthesis of Peptidomimetics,"As a new scaffold for peptidomimetic synthesis, a highly constrained bifunctional diketopiperazine, 4, has been prepared by smooth N-alkylation with tert-butyl bromoacetate. As a first application, we describe herein the synthesis of new peptidomimetics of the Arg-Gly-Asp (RGD) sequence. The product 30, which shows a selective platelet-aggregation inhibiting activity, can be used as a lead for the preparation of more potent products.",10.1002/(sici)1099-0690(199805)1998:5<853::aid-ejoc853>3.0.co;2-f,1998-05-01,0.604403083715555
Synthesis,"An Efficient Regioselective Synthesis of 2,4-Diarylfurans",,10.1055/s-1983-30218,1983-01-01,0.6043978658945686
Tetrahedron,Efficient regioselective synthesis of guanosine analogs,,10.1016/s0040-4039(00)61000-6,1992-10-01,0.6043978658945686
Journal of the American Chemical Society,Total Synthesis of Ganoapplanin Enabled by a Radical Addition/Aldol Reaction Cascade,"High Resolution Image Download MS PowerPoint Slide The total synthesis of the Ganoderma meroterpenoid ganoapplanin, an inhibitor of T-type voltage-gated calcium channels, is reported. Our synthetic approach is based on the convergent coupling of a readily available aromatic polyketide scaffold with a bicyclic terpenoid fragment. The three contiguous stereocenters of the terpenoid fragment, two of which are quaternary, were constructed by a diastereoselective, titanium-mediated iodolactonization. For the fusion of the two fragments and to simultaneously install the crucial biaryl bond, we devised a highly effective two-component coupling strategy. This event involves an intramolecular 6- exo -trig radical addition of a quinone monoacetal followed by an intermolecular aldol reaction. A strategic late-stage oxidation sequence allowed the selective installation of the remaining oxygen functionalities and the introduction of the characteristic spiro bisacetal structure of ganoapplanin.",10.1021/jacs.4c08291,2024-08-07,0.6043970099185625
Synthesis,A Short Synthesis of Albuterol,All articles of this category An efficient and useful synthesis of the title compound from salicylaldehyde is described.,10.1055/s-1988-27768,1988-01-01,0.6043909331639324
Organic Letters,Asymmetric Total Synthesis of (−)-Mycothiazole,"[structure: see text] In this Letter we describe the first total synthesis of mycothiazole, a polyketide thiazole from a marine sponge. Key steps include our CMD oxidation for the conversion of thiazolidine 11 to thiazole 12 and the Nagao acetate aldol reaction of 5 with aldehyde 4 to construct the chiral secondary alcohol. The skipped diene was constructed by the standard Stille coupling, and the conjugated diene was synthesized by lithium(I)- and copper(I)-mediated Stille coupling.",10.1021/ol000128l,2000-06-13,0.6043888910781857
Tetrahedron,Novel and efficient transformation of α-amino nitrile to α-imino and α-amide nitriles in asymmetric Strecker synthesis,,10.1016/s0040-4039(01)00551-2,2001-05-01,0.6043808999214689
Chemical Science,"Modular and diverse synthesis of oxaheterocycles <i>via</i> Pd-catalyzed migratory 1, <i>n</i> -cycloannulation of alkenes","-QM) intermediate during the migration process, which facilitates selective single-site cyclization at the less sterically hindered site and suppresses competing pathways. The synthetic utility of this strategy is further demonstrated by the efficient preparation of several bioactive oxaheterocyclic compounds including a cytotoxic flavan and an MRGPRX4 inhibitor, highlighting its potential in both synthetic and medicinal chemistry.",10.1039/d5sc06539a,2025-01-01,0.6043758411267894
Synlett,New Synthetic Routes toward Polyketide-like Macrolides,"New pathways toward the synthesis of polyketide-like macrolides have been developed through the functionalization of long chain polyolic fragments readily obtained from 3,3'-methylenebis{[6-(benzyloxy)methoxy]cyclohept-3-en-1-ol} derivatives 6. This synthetic route generates a large variety of stereoisomers and thus can be applied to the preparation of a library of polyhydroxylated macrocycles, analogues of natural bioactive macrolides.",10.1055/s-2006-932495,2006-01-01,0.6043682457622223
Organic Letters,Total Synthesis of (−)-Reveromycin A,The asymmetric total synthesis of (-)-reveromycin A is described. The key steps involved a Lewis acid catalyzed inverse electron demand hetero-Diels-Alder reaction followed by hydroboration/oxidation to afford the spiroketal core 4 in a highly stereoselective manner and introduction of the C18 hemisuccinate by high-pressure acylation.,10.1021/ol048811l,2004-07-22,0.6043675063769283
Tetrahedron,"An efficient synthesis of novel 2,4-disubstituted tetrahydroquinolines and quinolines",,10.1016/j.tetlet.2012.02.043,2012-02-26,0.6043662651903036
Organic Letters,Stereocontrolled Synthesis of the Sterically Encumbered F Ring of Lancifodilactone G,A stereochemically linear strategy has been developed to prepare the heavily congested F-ring sector of lancifodilactone G (1) from commercially inexpensive (R)-carvone. Prominent operations in our synthesis include Negishi-type sp2-sp3 cross-coupling and intramolecular free-radical cyclization for the purpose of appending the sidearm links of the D and H rings onto the F platform.,10.1021/ol800419v,2008-05-03,0.6043504720148037
European Journal of Organic Chemistry,Asymmetric Synthesis of Two Analogues of Meiogynin A,"Abstract The efficient and asymmetric synthesis of two analogues of meiogynin A, a natural sesquiterpenoid dimer that was recently isolated by our group, is reported. The key reaction was a highly selective intermolecular Diels–Alder reaction between an aromatic triene and two chiral dienes. This convergent synthesis maximizes the atom economy concept, as the expected compounds were obtained in only eight steps without any protecting groups.",10.1002/ejoc.201201628,2013-02-20,0.6043482191504385
Organic Letters,Rhodium(III)-Catalyzed Asymmetric C–H Activation of <i>N</i>-Methoxybenzamide with Quinone and Its Application in the Asymmetric Synthesis of a Dihydrolycoricidine Analogue,"A chiral CpRh III -catalyzed asymmetric C–H activation reaction of N -methoxybenzamides with quinones has been developed to efficiently forge chiral tricyclic hydrophenanthridinone scaffolds in ≤88% yield and ≤94% ee. With this methodology as the key step, an enantioenriched dihydrolycoricidine derivative has been synthesized in 64% overall yield in five steps.",10.1021/acs.orglett.0c01002,2020-04-02,0.6043438923010719
Organic Letters,Total Synthesis of (−)-Angiopterlactone B,"An enantioselective total synthesis of (-)-angiopterlactone B has been accomplished in four steps. The synthesis features a proposed biomimetic domino ring-contraction/oxa-Michael/Michael dimerization sequence, forming three new bonds, two new rings, and three new contiguous stereogenic centers in a single step. It has been determined that the originally proposed absolute configuration of natural (+)-angiopterlactone B needs revision. This reveals that angiopteroside, a known glycoside natural product, is the likely biosynthetic precursor to (+)-angiopterlactone B.",10.1021/acs.orglett.7b00929,2017-04-20,0.6043427153363358
Tetrahedron,Selenium-mediated glycosidations: A selective synthesis of β-2-deoxyglycosides,,10.1016/s0040-4039(01)80327-0,1989-01-01,0.6043274073228173
Tetrahedron,An efficient and stereospecific synthesis of novel pyrazine cnucleosides,,10.1016/0040-4039(95)01826-4,1995-11-01,0.6043024923680962
Journal of Organic Chemistry,A Short Synthesis of (+)-Narciclasine via a Strategy Derived from Stereocontrolled Epoxide Formation and SnCl<sub>4</sub>-Catalyzed Arene-Epoxide Coupling,"A facile construction of the typical framework of narcissus alkaloids has been realized by virtue of the development of a practical route involving stereocontrolled epoxide formation and SnCl(4)-catalyzed arene-epoxide coupling. To achieve this goal, it proved to be necessary to devise a strategy that would enable chemical transformations to install an epoxy moiety in a congested environment. The successful preparation of a hindered epoxide from O-isopropylidene-protected 4-aminocyclohexenol required three steps consisting principally of controlled bromohydration and base-promoted closure and N-alkylation. It was found that a catalytic amount of SnCl(4) not only maintained the catalytic cycle but also effected clean arylation to form a fused BC ring system. Several tactics that ultimately proved to be unsatisfactory are also discussed in an effort to set important boundary limits on arene-epoxide coupling. The requisite enantiopure 4-aminocyclohexenol was available via an asymmetric cycloaddition of diene to camphor-based chloronitroso. The total synthesis of (+)-narciclasine was realized in nine steps with an overall yield of 19%.",10.1021/jo020155k,2002-09-07,0.6042932857876715
Organic Letters,Access to Ring-Expanded Analogues of 2-Amino Sugars,"Ring-expanded 2-N-acetylamino sugar analogs of D-glucose, D-galactose, and D-mannose have been prepared by a new synthetic route. Aspects of the highly substituted alpha-amino aldehyde intermediates made them central to the approach. First, they were accessed via diastereoselective addition of a vinyl Grignard onto protected glycosyl amines. Also, the sterics of the bis-protected amine favored the formation of only one glycoside anomer. The new analogues reported here should prove useful in the development of tools to investigate the role of 2-amino sugars in biology.",10.1021/ol9018387,2009-09-01,0.6042786623087736
Tetrahedron,"A stereoselective synthesis of sphingosine, a protein kinase c inhibitor.",,10.1016/0040-4039(88)85079-2,1988-01-01,0.6042658853767964
Tetrahedron,"A stereoselective synthesis of (R)-5-hydroxy-3-(4-methoxyphenethyl)cyclohex-2-enone, towards total synthesis of Prelunularin",,10.1016/j.tetlet.2019.151134,2019-09-09,0.604257802951215
Angewandte Chemie International Edition,Concise Synthesis of Tunicamycin V and Discovery of a Cytostatic DPAGT1 Inhibitor,"A short total synthesis of tunicamycin V (1), a non-selective phosphotransferase inhibitor, is achieved via a Büchner-Curtius-Schlotterbeck type reaction. Tunicamycin V can be synthesized in 15 chemical steps from D-galactal with 21 % overall yield. The established synthetic scheme is operationally very simple and flexible to introduce building blocks of interest. The inhibitory activity of one of the designed analogues 28 against human dolichyl-phosphate N-acetylglucosaminephosphotransferase 1 (DPAGT1) is 12.5 times greater than 1. While tunicamycins are cytotoxic molecules with a low selectivity, the novel analogue 28 displays selective cytostatic activity against breast cancer cell lines including a triple-negative breast cancer.",10.1002/anie.202203225,2022-05-20,0.6042472421396681
Tetrahedron,"A stereoselective synthetic route to cis-2,5-disubstituted tetrahydrofurans",,10.1016/0040-4039(91)80615-d,1991-08-01,0.6042460671462653
Organic Letters,"Total Synthesis of a Cytotoxic Acetogenin, Pyranicin","[structure: see text] The first total synthesis of a new cytotoxic acetogenin, pyranicin (1), is described. SmI(2)-induced reductive cyclization of beta-alkoxy acrylate 4 proceeded stereoselectively to give 16,20-syn-19,20-trans-THP derivative 14, which was efficiently transformed into the 19,20-cis-THP derivative 18 through Mitsunobu lactonization. Wittig reaction of the phosphonium salt 2 obtained therefrom with butenolide 3 at -78 degrees C followed by reduction and deprotection afforded 1 in good overall yield.",10.1021/ol034323m,2003-03-27,0.6042446516663591
Synthesis,A Short Route to Heteroarylcarbazoles: Synthesis of New Pyrazolylcarbazoles and Carbazolylquinolines,A short synthesis of pyrazolylcarbazoles from 9-alkylcarbazoles in three steps is reported. The acetylcarbazoles prepared by the acetylation of carbazoles with acetic anhydride catalyzed by BiCl3 were converted into chloroaldehydes with Vilsmeier reagent. Condensation of chloroaldehydes with hydrazine followed by cyclization yield the pyrazolylcarbazoles. Carbazolyl chalcones were prepared by the condensation of carbazole-3-aldehyde with o-aminoacetophenone and cyclized to carbazolylquinolone using several catalysts. Cyclization of carbazolyl chalcones with the Vilsmeier reagent yields a mixture of carbazolylquinoline carbaldehydes.,10.1055/s-2004-822353,2004-01-01,0.604238298658976
Journal of the American Chemical Society,The Neber Route to Substituted Indoles,"Two complementary procedures have been developed for the conversion of the oximes of alpha-aryl ketones to azirines. On heating, the azirines rearrange smoothly to the corresponding indoles. The overall transformation offers a versatile route to indoles, complementary to the Fischer indole synthesis.",10.1021/ja058026j,2006-01-06,0.604234251938076
Journal of the American Chemical Society,Total Synthesis of Cytotoxic Macrolide Amphidinolide B<sub>1</sub> and the Proposed Structure of Amphidinolide B<sub>2</sub>,"The first enantioselective total syntheses of cytotoxic macrolide amphidinolide B1 and the proposed structure for amphidinolide B2 have been accomplished. Key features of the syntheses include a diastereoselective aldol condensation, a spontaneous Wadsworth-Emmons macrocyclization and a directed epoxidation/elimination sequence.",10.1021/ja803012n,2008-05-20,0.6042320514436758
Journal of Organic Chemistry,Total Synthesis of the <i>Melodinus</i> Alkaloid (±)-Melohemsine K,"The first total synthesis of the novel Melodinus alkaloid melohemsine K is described in five steps from known precursors. The key reaction of the synthesis is a tandem enamine formation/retro-aza-Michael reaction/Diels–Alder cycloaddition/intramolecular lactamization reaction cascade between indole-fused azepine and aldehyde precursors, forging the critical CDE tricyclic system. The synthesis provided a general approach to novel Melodinus alkaloids.",10.1021/acs.joc.5c00545,2025-04-25,0.6042294014781336
European Journal of Organic Chemistry,Total Synthesis of (+)‐Aspicilin by an Alkyne‐Based Approach and Its Biological Evaluation,"Abstract The stereoselective total synthesis of (+)‐aspicilin is described. The pivotal step in this approach is the generation of an enyne intermediate by the coupling of an alkyne with vinyl iodide, which constructed the C6–C7 bond. Conversion of the enyne to the desired macrolide was achieved through Sharpless asymmetric dihydroxylation and Yamaguchi macrolactonization as the key steps. Additionally, the biological activity of (+)‐aspicilin was evaluated on A549, HeLa, and MCF7 cancer cell lines.",10.1002/ejoc.201101673,2012-02-03,0.604226993432297
Organic Process Research & Development,Economical and Practical Process Development for a Novel Multitarget Tyrosine Kinase Inhibitor Vorolanib,"Vorolanib (X-82, CM082) is a novel multitarget tyrosine kinase inhibitor that effectively inhibits the activity of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and FMS-like tyrosine kinase-3 (FLT-3) receptors. Vorolanib is currently accessible in the Chinese market, and its approved indication is combined with Everolimus for patients with advanced renal cell carcinoma (RCC) who have previously failed tyrosine kinase inhibitor (TKI) treatment. Here, we have developed an economical and practical process for Vorolanib, which exhibits low cost, high yield, simple post-treatment, and environmental protection based on extensive investigations into synthesis methods (raw materials, temperature, coupling reagent, solvent, reaction time, post-treatment, etc.). This process was successfully used to prepare Vorolanib with a total yield of 67.1% and a purity of 99.97%, and no chiral degradation occurred during the synthesis. All intermediates were confirmed by ESI-MS and 1 H NMR, whereas the target compounds were confirmed by ESI-MS, 1 H NMR, and 13 C NMR.",10.1021/acs.oprd.3c00311,2024-01-18,0.6042249190937199
Organic Letters,Total Synthesis of (±)-Impatien A via Aza-Heck Cyclization,"The first total synthesis of the natural product impatien A is described. This concise synthesis features an aza-Heck cyclization to construct the complex spirocyclic ring system and provides a rare example of the use of aza-Heck cyclizations in complex molecule synthesis. To enable this key cyclization of an electrophilic nitrogen atom with a tetrasubstituted alkene, we utilized high-throughput experimentation to identify a new ligand and ultimately deliver impatien A in seven steps from known compounds.",10.1021/acs.orglett.1c02767,2021-08-30,0.6042185176157464
Journal of Organic Chemistry,Concise Syntheses of (+)-Macrosphelides A and B: Studies on the Macro-Ring Closure Strategy,"Highly concise syntheses of (+)-macrosphelides A and B were accomplished in this study. The key feature of our synthetic route involved the direct three-carbon homologation of the readily available Weinreb amide 6 by the addition of a trans-vinylogous ester anion equivalent and facile construction of the 16-membered macrolide skeleton of macrosphelides via an intramolecular nitrile oxide-olefin cycloaddition. The syntheses of macrosphelides A and B were completed with a 30 and 20% overall yield, respectively. This paper describes the details of our syntheses.",10.1021/jo8016692,2008-12-16,0.6042138775510177
Tetrahedron,"A new route for the synthesis of substituted benzo [1,3,4] oxadiazine derivatives via copper-catalyzed N-arylation-cyclization of hydrazonoyl chlorides and 2-iodophenol",,10.1016/j.tetlet.2024.155333,2024-10-18,0.6042132986394045
Journal of the American Chemical Society,Convergent Total Synthesis of Aleutianamine,"Herein, we describe a convergent total synthesis of the pyrroloiminoquinone natural product aleutianamine that exemplifies a novel paradigm for pyrroloiminoquinone synthesis by hinging upon a convergent intermolecular carbon-carbon bond forming event. Specifically, the coupling of a pyrroloquinone monoketal and a siloxythiophene fragment, each prepared in seven steps from commercially available materials, allows for access to the entire carbon framework of aleutianamine in only eight steps. A variety of intriguing skeletal rearrangements, minimal late-stage redox adjustments, and a carefully choreographed sequence of carbon-nitrogen bond formations then deliver the natural product.",10.1021/jacs.4c12946,2025-02-07,0.6042085477929381
Angewandte Chemie International Edition,Total Synthesis of the Proposed Structure of Neaumycin B,"The total synthesis of the proposed structure of anti-glioblastoma natural product neaumycin B was achieved in 22 steps (longest linear sequence). The synthesis features HCl-mediated [6,6]-spiroketalization, a combination of Krische iridium-catalyzed crotylation, Marshall palladium-catalyzed propargylation, Fürstner nickel-catalyzed regio- and enantioselective vicinal monoprotected diol formation, Brown crotylation and asymmetric halide-aldehyde cycloaddition, so as to establish the challenging contiguous stereocenters.",10.1002/anie.202313186,2023-10-27,0.6042076317915803
Organic Letters,Total Synthesis and Conformational Analysis of the Antifungal Agent (−)-PF1163B,"[reaction: see text]. (-)-PF1163B, a new macrocyclic antifungal antibiotic isolated from Streptomyces sp., has been prepared in eight steps from (S)-citronellene. The key step is a ring-closing metathesis reaction of an ester and amide derivative obtained from a substituted N-methyl-l-tyrosine.",10.1021/ol035309c,2003-09-27,0.6042020926155435
Angewandte Chemie International Edition,"Bio‐Inspired Fragmentations: Rapid Assembly of Indolones, 2‐Quinolinones, and (−)‐Goniomitine","Inspired by the biogenetic origin of goniomitine, new synthetic bio-inspired fragmentation strategies for the synthesis of functionalized 2-quinolinones and indolones have been developed. Remarkable synthetic efficiency was achieved by telescoping several transformations into one-pot reactions, allowing for the direct coupling of 2-alkynyl-anilines and diazo ketones. The synthetic utility was demonstrated by the 5-step asymmetric total synthesis of (-)-goniomitine from 2-ethyl-cyclopentanone.",10.1002/anie.201611830,2017-01-27,0.6042004562194838
Synthesis,A Concise Total Synthesis of (±)-Camptothecin,"A total synthesis of racemic camptothecin, characterized by a concise construction of the ring systems and easy functional group transformation, is described. A domino reaction consisting of a Heck reaction and an aza-intramolecular Michael addition to form the C ring serves as the first key step in the synthesis. The D ring was constructed by a simple Wittig–Horner reaction followed by removal of the protective groups. Hydroxymethylation, demethylation, and lactone formation reactions were performed in one-pot to construct the E ring under hydrobromic acid conditions. This work provides an efficient scheme for further synthetic exploration of camptothecin and its analogues.",10.1055/s-0037-1611870,2019-06-26,0.6041967040731996
Synthesis,A Facile Total Synthesis of (±)-Acoragermacrone by Titanium-Induced Keto Ester Cyclization,"All articles of this category (±)-Acoragermacrone, a naturally occurring germacrane-type sesquiterpenoid, was synthesized from geranyl acetate via five steps by employing titanium-induced intramolecular coupling, involving a α,β-unsaturated keto ester, as the key step.",10.1055/s-1994-25455,1994-01-01,0.604190195497678
Organic Letters,Synthesis of Desacyl Furanmonogones A and B,"A strategy for the stereoselective synthesis of desacyl furanmonogones A and B has been achieved. The key steps in this synthesis are (1) an Fe(ClO 4 ) 3 -mediated oxidative radical cyclization for construction of a cis -fused [5–6]-bicyclic core with a bridged lactone substitute, (2) a phosphorane-mediated rearrangement to convert the cis -fused [5–6]-bicyclic core to the corresponding trans -fused [5–6]-bicyclic core, and (3) a Au-catalyzed cascade reaction for formation of the 4,5- seco -3(2 H )-furanone motif.",10.1021/acs.orglett.1c01157,2021-04-29,0.6041826424453215
Journal of Organic Chemistry,Total Synthesis of Narbonolide and Biotransformation to Pikromycin,An improved total synthesis of narbonolide and its biotransformation to pikromycin is reported. This total synthesis utilized an intramolecular Nozaki-Hiyama-Kishi coupling that significantly improved macrocyclization yields (90-96%) and allowed for differentiation of the C3- and C5-oxidation states. A pikAI deletion mutant of Streptomyces venezuelae was used to biotransform synthetic narbonolide to pikromycin by glycosylation and oxidation in vivo. This integration of synthetic chemistry and engineered biotransformations holds great promise for the synthesis of novel macrolide analogues of biological interest.,10.1021/jo062047u,2006-11-22,0.6041823667947781
Journal of Organic Chemistry,Diastereoselective Zwitterionic Aza-Claisen Rearrangement:  The Synthesis of Bicyclic Tetrahydrofurans and a Total Synthesis of (+)-Dihydrocanadensolide,"The zwitterionic Claisen rearrangement of optically-active N-allyl pyrrolidines and various acid chlorides proceeds with high simple diastereoselection (internal asymmetric induction) and high 1,2-asymmetric induction, generating a new C-C bond adjacent to a chiral C-O function. The resulting gamma,delta-unsaturated amides were cyclized to the corresponding optically active gamma-butyrolactones, which are useful intermediates in natural product synthesis. On one hand, a diastereoselective iodocyclization of several lactones led to tetrahydrofurans with a substitution pattern representing a key intermediate of an oxa-prostaglandin synthesis. On the other, a one-pot procedure of a Swern oxidation and consecutive Grignard reaction of one gamma-lactone allowed a diastereoselective chain elongation. The final oxidation/cyclization sequence completed a highly efficient synthesis of the (+)-dihydrocanadensolide or its C-3 epimer, respectively.",10.1021/jo9600464,1996-01-01,0.6041771601442374
Synlett,"A Cyclobutanol Ring-Expansion Approach to Oxygenated Carbazoles: Total Synthesis of Glycoborine, Carbazomycin A and Carbazomycin B","Abstract The transition-metal-free total syntheses of the oxygenated carbazole natural products glycoborine, carbazomycin A and carbazomycin B are reported. The key step involves an NBS-mediated cyclobutanol ring expansion to 4-tetralones for the preparation of the tricyclic carbazole core.",10.1055/s-0042-1751411,2023-01-24,0.6041738760482578
Organic Process Research & Development,"Process Research, Development, and Pilot-Plant Preparation of Clofencet, a Novel Wheat Hybridizing Agent:  Lewis Acid-Catalyzed Reaction of Ethyl Diazoacetate with 4-Chlorophenyl Hydrazonoacetaldehyde","Described are studies directed toward the chemical research and development of an alternative synthesis to 9, the penultimate intermediate of clofencet ( 1 ), a novel wheat-hybridizing agent. Retrosynthetic analyses as well as the results obtained from feasibility studies are detailed, leading to the successful development of an alternative process. The key features of the novel route are a method for preparing on-scale ethyl diazoacetate ( 28 ) in a safe and effective manner, and the Lewis acid-catalyzed reaction of 28 with hydrazonoacetaldehyde 29, affording β-ketoester 30 . The synthesis is completed via propionylation of 30, acid-catalyzed cyclization of 31 to pyridazinecarboxylic acid ester 32, followed by saponification and isolation of carboxylic acid 9 . The results and challenges of eight pilot-plant runs are reported. The baseline process developed produced over 45 kg of 9 in 43−45% yield.",10.1021/op034123q,2004-01-30,0.6041733494173913
Journal of Organic Chemistry,Synthesis of Spirolactams and Fused Bicyclic Lactams via Acid-Promoted Cyclolactamization of (Ethynyl(tosyl)amino)methyl-Tethered Cyclohex-2-enols,"A simple synthetic method to construct the spirolactam framework from TfOH-catalyzed spirolactamization of cyclohex-2-enols bearing a tethered (arylethynyl(tosyl)amino)methyl moiety is described. The reaction proceeded through a keteniminium–allylic carbocation intermediate. Hydration of the keteniminium ion, followed by attack of the resulting enolate onto the tethered allylic carbocation, provided the spirolactam ring skeleton. This strategy could also be employed in the synthesis of fused bicyclic lactams from BF 3 ·OEt 2 -assisted cyclolactamization of TBS-protected 2-(ethynyl(tosyl)amino)methylcyclohex-2-enols.",10.1021/acs.joc.7b02158,2017-10-09,0.6041708239622294
Synthesis,"New Aspects of Stereoselective Synthesis of 1,3-Polyols","All articles of this category Recent progress in the methodology for stereoselective synthesis of the 1,3-polyol functions is reviewed. Strategies for the synthesis of the extended 1,3-polyol chain are also described. 1 . Introduction 2. New Synthetic Methodologies for 1,3-Polyols 2.1. Stereoselective Functionalization of Homoallylic Alcohols 2.1.1. Route via a Cyclic Iodo Carbonate 2.1.2. A Reiterative Strategy Involving Homoallylic Alcohol Epoxidation Followed by Ring Opening with a Higher Order Mixed Organocuprate 2.1.3. Direct Functionalization of Homoallylic Alcohols 2.2. Synthesis Based on Functionalization of Allylic Alcohols and Related Compounds 2.2.1. A Reiterative Strategy Involving the Sharpless Asymmetric Epoxidation of Allylic Alcohols Followed by Regioselective Epoxide Reduction 2.2.2. Route via lodohydrins 2.2.3. Route via Hydroboration of Allylsilanes 2.3. Synthesis of syn -1,3-Polyols via Peroxides 2.4. Reduction of Acyclic ß-Hydroxy Ketones 2.4.1. Synthesis of syn -1,3-Diols 2.4.2. Synthesis of anti -1,3-Diols 2.5. Reduction of Cyclic Ketone Equivalents of Acyclic ß-Hydroxy Ketones 2.6. Synthesis of 1,3-Diols by Carbon-Carbon Bond Formation 2.6.1. Alkylation of ß-Alkoxy Aldehydes 2.6.2. Dialkylation of 1,3-Dioxins 2.6.3. Intramolecular Reformatsky-Type Reactions 2.6.4. The [1,2]-Wittig Rearrangement of ß-Alkoxyalkyl Allyl Ethers 2.6.5. Hydroxylation of 4-Butanolides with Bulky Substituents in Position 4 3. A Strategy for the Synthesis of Extended 1,3-Polyol Chains 3.1. Two-Directional 1,3-Polyol Chain Extension Strategy 3.2. Convergent Synthesis of the Extended Polyol Chain 3.2.1 Alkylation of Carbonyl Anion Equivalents Followed by Stereoselective Reduction of the Resulting Ketone 3.2.2. Coupling of Two Different Aldehydes Mediated by Carbonyl Dianion Equivalents Followed by Ancillary Stereocontrol 4. Conclusion",10.1055/s-1990-26966,1990-01-01,0.604170736108782
Tetrahedron,Synthesis of a new neurotoxin NSTX-3 of Papua New Guinean spider,,10.1016/s0040-4039(00)96339-1,1987-01-01,0.6041694706757941
Synlett,"Synthesis of the Reported Structure of Crassiflorone, a Pentacyclic Naphthoquinone Isolated from the African Ebony Diospyros crassiflora","A short synthesis of the furocoumarin naphthoquinone structure reported for the natural product crassiflorone is described, in which the key steps are a Diels-Alder reaction to form 2-bromo-8-hydroxy-6-methylnaphthoquinone, followed by O-protection and copper(II)-mediated coupling to 4-hydroxy-5-methylcoumarin to establish the pentacyclic framework.",10.1055/s-0029-1218578,2009-12-17,0.6041667075050219
Journal of the American Chemical Society,Design and Synthesis of Chiral <i>oxa</i>-Spirocyclic Ligands for Ir-Catalyzed Direct Asymmetric Reduction of Bringmann’s Lactones with Molecular H<sub>2</sub>,"We herein present a facile and column-free synthetic route toward a structurally unique oxa-spirocyclic diphenol, termed as O -SPINOL. Features of the synthesis include the construction of the all-carbon quaternary center at an early stage, a key double intramolecular S N Ar step to introduce the spirocycles and the feasibility of operating on >100 g scale. Both enantiomers of O -SPINOL can be easily accessed through optical resolution with l -proline by control of the solvent. The chiral tridentate ligand O -SpiroPAP derived from O -SPINOL has been successfully synthesized and applied in the iridium-catalyzed asymmetric hydrogenation of bridged biaryl lactones under mild reaction conditions, providing valuable and enantioenriched axially chiral molecules in excellent yields and enantioselectivities (up to 99% yield and >99% ee). This method represents a rare example of constructing axially chiral molecules by direct reduction of esters with H 2 .",10.1021/jacs.8b03642,2018-06-19,0.6041640402842547
European Journal of Organic Chemistry,Synthetic Application of Sequential Palladium-Catalyzed Allylic Acetate Alkylation and Michael Addition Carbocyclization: Synthesis of (±)-Dihydroerythramine,"A new synthetic route to aromatic Erythrina alkaloids is reported. (Nitromethyl)arene 3 underwent a palladium-catalyzed annulation reaction with allylic acetate 11 to provide nitro esters 12a and 12b by an (η3-allyl)palladium complex alkylation/Michael addition domino sequence. Reduction of the nitro group of 12a, followed by cyclization of the resulting amino group on the acetate appendage, afforded the bicyclic lactam 29. Two-carbon elongation at the nitrogen atom of 29 by hetero Michael addition of vinyl phenyl sulfoxide, followed by Pummerer-type cyclization, gave cis-11-phenylthioerythrinan-8-one (32a, 32b) along with the rearranged lactam 34. Reductive desulfurization at C-11, and oxidative cleavage of the C-3 exocyclic double bond afforded the 15,16-(methylenedioxy)erythrinan-3,8-dione (42). Reduction of the C-3 carbonyl group and methylation of the resulting alcohol afforded hexahydrocrystamidine (44), which was further reduced by aluminum hydride to give (±)-dihydroerythramine (9).",10.1002/1099-0690(200110)2001:19<3631::aid-ejoc3631>3.0.co;2-8,2001-10-01,0.6041554459989281
Angewandte Chemie International Edition,An Efficient Route to Polysubstituted Tetrahydronaphthols: Silver‐Catalyzed [4+2] Cyclization of 2‐Alkylbenzaldehydes and Alkenes,"Silver bullet: A methodology for stereoselective synthesis of polysubstituted tetrahydronaphthols catalyzed by [Ag+]/NPO has been developed. The reactions proceeded through an unprecedented [4+2] cyclization of 2-(2-formylphenyl)ethanone and an alkene, in both inter- and intramolecular fashion. NPO=pyridine N-oxide.",10.1002/anie.201204798,2012-09-26,0.6041538322540396
Journal of Organic Chemistry,Synthesis of Stereopentad Subunits of Zincophorin and Rifamycin-S through Use of Chiral Allenyltin Reagents,"The anti,anti adduct 3, from addition of the allenic stannane ( P )- 2 to the α-methyl-β-OBn aldehyde ( S )- 1 promoted by SnCl 4, was converted to the stereopentad 6 by a sequence involving reduction to the ( E )-allylic alcohol with Red-Al, Sharpless asymmetric epoxidation, and addition of the higher-order methyl cyanocuprate to the derived epoxide 5 . Stereopentad 6 was converted to the acetonide acetal 15, an intermediate in Danishefsky's synthesis of zincophorin. By a similar sequence, adduct ent - 4 was converted, via diol 19, to stereopentad 22, an intermediate in Kishi's synthesis of rifamycin-S. An alternative route to diol 19 was achieved from the MOM-protected derivative 28 of epoxy diol 18 .",10.1021/jo980137w,1998-05-01,0.6041504353230124
Synthesis,"Total Synthesis of Methyl 1,5,8-Trimethoxy-1H-isochromene-3-carboxylate and Its Derivatives via Palladium-Catalyzed Annulation of 2-Alkynylbenzaldehydes","Abstract A 7-step total synthesis of methyl 1,5,8-trimethoxy-1H-isochromene-3-carboxylate and a 5-step synthesis of its C-3 derivatives are reported. Sonogashira coupling of 2-halobenzaldehydes with terminal acetylenes was employed to access 2-alkynylbenzaldehydes, which underwent a Pd-catalyzed annulation to afford the corresponding isochromene-containing products.",10.1055/a-1532-8656,2021-06-21,0.6041423826183555
Journal of Organic Chemistry,A Practical and Efficient Route for the Highly Enantioselective Synthesis of Mexiletine Analogues and Novel β-Thiophenoxy and Pyridyl Ethers,A practical and efficient procedure for the enantioselective synthesis of mexiletine analogues with use of 10% of spiroborate ester 6 as chirality transfer agent is presented. A variety of mexiletine analogues were prepared in good yield with excellent enantioselectivities (91-97% ee) from readily available starting materials. The developed methodology was also successfully applied for the synthesis of novel beta-amino ethers containing thiophenyl and pyridyl fragments.,10.1021/jo801181d,2008-08-09,0.6041398158324808
Organic Letters,"Enantiopure 1,4-Benzoxazines via 1,2-Cyclic Sulfamidates. Synthesis of Levofloxacin","1,2-Cyclic sulfamidates undergo efficient and regiospecific nucleophilic cleavage with 2-bromophenols (and related anilines and thiophenols), followed by Pd(0)-mediated amination to provide an entry to substituted and enantiomerically pure 1,4-benzoxazines (and quinoxalines and 1,4-benzothiazines). This chemistry provides a short and efficient entry to (3S)-3-methyl-1,4-benzoxazine 19, a late stage intermediate in the synthesis of levofloxacin.",10.1021/ol0712475,2007-07-28,0.6041293871525555
Journal of Organic Chemistry,Synthesis of AD-Dihydrodipyrrins Equipped with Latent Substituents of Native Chlorophylls and Bacteriochlorophylls,"Native chlorophylls and bacteriochlorophylls share a common trans -substituted pyrroline ring D (17-propionic acid, 18-methyl), whereas diversity occurs in ring A particularly at the 3-position. Two dihydrodipyrrins equipped with native-like D-ring substituents and tailorable A-ring substituents have been synthesized. The synthesis relies on a Schreiber-modified Nicholas reaction to construct the stereochemically defined precursor to ring D, a dialkyl-substituted pent-4-ynoic acid. The carboxylic acid group of the intact propionic acid proved unworkable, whereupon protected propionate (−CO 2 t Bu) and several latent propyl ethers were examined. The tert -butyldiphenylsilyl-protected propanol substituent proved satisfactory for reaction of the chiral N -acylated oxazolidinone, affording (2 S,3 S )-2-(3-(( tert -butyldiphenylsilyl)oxy)propyl)-3-methylpent-4-ynoic acid in ∼30% yield over 8 steps. Two variants for ring A, 2- tert -butoxycarbonyl-3-Br/H-5-iodo-4-methylpyrrole, were prepared via the Barton–Zard route. Dihydrodipyrrin formation from the pyrrole and pentynoic acid entailed Jacobi Pd-mediated lactone formation, Petasis methenylation, and Paal–Knorr-type pyrroline formation. The two AD-dihydrodipyrrins bear the D-ring methyl and protected propanol groups with a stereochemical configuration identical to that of native (bacterio)chlorophylls, and a bromine or no substitution in ring A corresponding to the 3-position of (bacterio)chlorophylls. The analogous β-position of a lactone–pyrrole intermediate on the path to the dihydrodipyrrin also was successfully brominated, opening opportunities for late-stage diversification in the synthesis of (bacterio)chlorophylls.",10.1021/acs.joc.1c01239,2021-08-04,0.6041252593958469
European Journal of Organic Chemistry,A One-Pot Synthesis of New Macrocyclic Compounds with Tetraaminoethene Substructure,"A convienent one-pot synthesis of macrocycles containing a tetraaminoethene substructure is described. Starting from oxalic amidines 1, reduction with lithium and subsequent addition of phenyl isothiocyanate afforded the anionic bis(thiocarbamoyl) derivatives 3. In the final step, a ring-closure reaction using a large number of α,ω-dielectrophilic building blocks yields the new macrocyclic compounds 6-14.",10.1002/(sici)1099-0690(199809)1998:9<1803::aid-ejoc1803>3.0.co;2-l,1998-09-01,0.6041091864616094
Journal of Organic Chemistry,Practical Asymmetric Synthesis of Chiral Sulfoximines via Sulfur-Selective Alkylation,"Chiral sulfoximines have recently been considered as promising bioisosteres in medicinal chemistry. However, methods for preparing chiral sulfoximines in a stereoselective manner are underdeveloped. Herein, we demonstrate an asymmetric synthesis of chiral sulfoximines through a stereospecific S -alkylation of readily accessible chiral sulfinamides under practical conditions. A key to establishing the practical conditions was the identification of the intermediate structure in our previously reported S -alkylation by X-ray crystallographic analysis.",10.1021/acs.joc.1c02424,2022-01-25,0.6041072010812134
Synlett,New Highly Diastereoselective Synthesis of Phosphoramidates. A Route to Chiral Methyl<i>p</i>-Nitrophenyl Alkylphosphonates,"All articles of this category A new, efficient and highly enantioselective synthesis of methyl p -nitrophenyl alkylphosphonates 4 a - c is described. Alkylphosphonic dichloride 1 a - d reacted successively with L-proline ethyl ester and p -nitrophenol to afford phosphoramidates 3 a - d in 97% de. Boron trifluoride catalysed methanolysis gave 4 a - c with 93% ee. Absolute configurations of compounds 4 c and 3 c were established by correlation with the X-ray structure of HPL-colipase-(-)- 4 c complex. 31 P NMR studies indicates that monochloro phosphoramidates ( R p )- and ( S p )- 2 c undergo fast epimerisation. The observed diastereoselectivity in favour of ( S p )- 3 c results from a faster reaction of ( R p )- 2 c as compared to its epimer, according to the Curtin-Hammett principle. asymmetric synthesis - alkylphosphonates - enantioselectivity - L-proline derivatives",10.1055/s-1998-1560,1998-01-01,0.6041054691379797
Organic Letters,"Asymmetric Total Synthesis of an Iboga-Type Indole Alkaloid, Voacangalactone, Newly Isolated from <i>Voacanga africana</i>","A new hexacyclic iboga-type indole alkaloid, voacangalactone (1), was isolated from Voacanga africana , and its structure including the absolute configuration was established by asymmetric total synthesis involving such key steps as the asymmetric Diels-Alder reaction using an aminodiene and the construction of an isoquinuclidine ring and an indole skeleton.",10.1021/ol3027945,2012-11-06,0.6041001265502127
Journal of Organic Chemistry,Asymmetric Synthesis of the Four Possible Fagomine Isomers,"The asymmetric synthesis of fagomine and its congeners 1-4 has been achieved by catalytic ring-closing metathesis (RCM). The synthesis involved the construction of the piperidene-type chiral building block 5 followed by dihydroxylation, starting from the d-serine-derived Garner aldehyde 6.",10.1021/jo034137u,2003-04-02,0.604085671470943
Journal of Organic Chemistry,Convenient Synthesis of 1 → 3 <i>C</i>-Branched Dendrons,"A facile, efficient synthesis of 1 --> 3 C-branched polyamide dendrons is described. Treatment of acryloyl chloride with 1 --> 3 C-branched amines, e.g., di-tert-butyl 4-[2-(tert-butoxycarbonyl)ethyl]-4-aminoheptanedioate, gave the corresponding acrylamides in high yields, which upon reaction with nitromethane generated the homologated nitroalkane-polyesters. Finally, nitroalkane alkylation with 2 equiv of the acrylamides, followed by nitro group reduction, afforded the desired amino-polyesters.",10.1021/jo0504518,2005-05-17,0.6040822112862101
Journal of Organic Chemistry,Total Synthesis of (+)-Cryptocaryol A Using a Prins Cyclization/Reductive Cleavage Sequence,"The total synthesis of (+)-cryptocaryol A was achieved in 20 steps from (R)-glycidol. The key steps were a Prins cyclization/reductive cleavage sequence to construct the C5-C11 polyol fragment, a diastereoselective aldol reaction to control the stereogenic center at C13, and a stereocontrolled reduction to introduce the stereogenic center at C15.",10.1021/acs.joc.5b01323,2015-08-04,0.6040807754942957
Synthesis,Convenient Synthesis of Ethenylcyclopropane and Some 2-Cyclopropylcyclopropane Derivatives¹,"Ethenylcyclopropane (5) was prepared from cyclopropyl methyl ketone (1) in four simple, easily scalable steps (bromination, reduction to the bromohydrin, acetylation of the latter, and reductive elimination with Zn/Cu) in an overall yield of 56%. 1-Bromo-2-cyclopropylcyclopropane (7) (approximately 1:1 mixture of cis- and trans-7) was prepared from 5 via the dibromide 6, and from 7 the boronate cis/trans-8 (ratio 1:1) was obtained in 96% yield. Rhodium(II)-catalyzed cyclopropanation of 5 with ethyl diazoacetate gave ethyl 2-cyclopropylcyclopropanecarboxylate (cis/trans-9, ratio 1:1.4) in 80% yield. The latter was also prepared in 79% overall yield by sequential cyclopropanation of buta-1,3-diene with ethyl diazoacetate [under Rh2(OAc)4 catalysis] and diiodomethane/diethylzinc/trifluoroacetic acid. Curtius degradation of 2-cyclopropylcyclopropanecarboxylic acid (obtained by hydrolysis of the ester) gave 2-cyclopropylcyclopropanamine (1:1.2 mixture of cis- and trans-isomers) in 58% yield.",10.1055/s-0031-1289600,2011-11-11,0.6040745130560738
Tetrahedron,Enantioselective protonation of prochiral enolates in the asymmetric synthesis of (S)-naproxen,,10.1016/s0040-4039(03)00217-x,2003-03-01,0.6040681183535499
Tetrahedron,"Enantioselective synthesis of the 6,8-dioxabicyclo-[3.2.1]octane skeleton by asymmetric dihydroxylation",,10.1016/s0040-4039(00)60985-1,1992-10-01,0.6040681183535499
Tetrahedron,Corrigendum to “Enantioselective protonation of prochiral enolates in the asymmetric synthesis of (S)-naproxen”,,10.1016/j.tetlet.2004.12.106,2005-01-13,0.6040681183535499
Tetrahedron,"The efficient consecutive β-carboxylation and α-alkylation of cyclic α,β-enones; a new route to sarkomycin",,10.1016/s0040-4039(00)96066-0,1987-01-01,0.6040614620336252
Journal of Organic Chemistry,Chiral Holmium Complex-Catalyzed Synthesis of Hydrocarbazole from Siloxyvinylindole and Its Application to the Enantioselective Total Synthesis of (−)-Minovincine,The catalytic and enantioselective total synthesis of (-)-minovincine has been accomplished. The key highly substituted hydrocarbazole derivative was obtained by an asymmetric Diels-Alder reaction of siloxyvinylindole catalyzed by 0.5 mol % of a chiral holmium complex. The Diels-Alder adduct was converted to a tetracyclic intermediate in a one-pot procedure. No waste stereoisomers were produced throughout the entire total synthesis.,10.1021/acs.joc.5b01393,2015-08-06,0.6040551447003681
Tetrahedron,Corrigendum to “Enantioselective total synthesis of pyrroloquinolone as a potent PDE5 inhibitor” [Tetrahedron Lett. 50 (2009) 520],,10.1016/j.tetlet.2009.03.090,2009-04-08,0.6040548207931268
Organic Letters,Synthesis of a Potent hNK-1 Receptor Antagonist via an S<sub>N</sub>2 Reaction of an Enantiomerically Pure α-Alkoxy Sulfonate,"The concise synthesis of a stereochemically rich hNK-1 receptor antagonist is described. The synthesis is highlighted by an S(N)2 reaction of an enantiomerically pure alpha-alkoxy sulfonate (orthogonally protected butane triol), which was prepared by utilizing salen-mediated hydrolytic kinetic resolution technology. A stereocontrolled acetalization was employed to connect two enantiomerically pure fragments with a high degree of diastereoselectivity.",10.1021/ol047925u,2004-12-09,0.604046450219603
Journal of Organic Chemistry,A direct synthesis of racemic demethoxyaflatoxin B2,"Aflatoxin analogue 19 was prepared by a direct sequence involving a novel silver-mediated cyclization to 12, the Michael addition of 16 with 17, and the oxidation of the Michael addition adduct. The overall yield of this six-step route is approximately 11%. The pathway is a flexible one that will permit the synthesis of analogues for toxicological analysis.",10.1021/jo00019a042,1991-09-01,0.6040406524945402
Tetrahedron,Selective reduction of the carbonyl group in organomercurials. A facile method for the protection-deprotection of the mercurio group and a new route to annulated lactones,,10.1016/0040-4039(96)01131-8,1996-07-01,0.6040202184688738
Angewandte Chemie International Edition,"Concise Total Synthesis of (−)‐Quinocarcin Enabled by Catalytic Enantioselective Reductive 1,3‐Dipolar Cycloaddition of Secondary Amides","Abstract A concise asymmetric total synthesis of (−)‐quinocarcin has been accomplished with high step economy from commercially available starting materials. A catalytic enantioselective reductive 1,3‐dipolar cycloaddition reaction of N ‐heteroaryl secondary amides with reactive dipolarophiles using iridium/copper relay catalysis was developed to prepare the key chiral pyrrolidine intermediate with three stereocenters. This protocol features excellent regio‐, exo ‐ and enantioselectivities, broad substrate scope, and good functional group tolerance. The high efficiency was also ensured by a Rh III ‐catalyzed C−H activation/cyclization and a tandem diastereoselective hydrogenation/cyclization to construct the tetrahydroisoquinoline‐pyrrolidine tetracyclic core unit of quinocarcin.",10.1002/anie.202302832,2023-04-07,0.6040200762607224
European Journal of Organic Chemistry,A Concise Stereoselective Synthesis of the Tetracyclic Naphthoquinone (–)‐Isagarin,Abstract A concise stereoselective synthesis of the tetracyclic naphthoquinone natural product (–)‐isagarin has been completed in seven steps from known alkyne 5 (obtained from D ‐mannitol) by using Dötz benzannulation and intramolecular stereospecific dioxabicyclic ketal formation as key steps.,10.1002/ejoc.201101279,2011-10-13,0.6040164651457895
Tetrahedron,A concise one-step synthesis of primin and iso-primin,,10.1016/j.tetlet.2015.03.073,2015-04-01,0.6040046199724224
Organic Letters,Approaches to<i>N</i>-Methylwelwitindolinone C Isothiocyanate: Facile Synthesis of the Tetracyclic Core,"The synthesis of a functionalized, tetracyclic core of N-methylwelwitindolinone C isothiocyanate is reported. The approach features a convergent coupling between an indole iminium ion and a highly functionalized vinylogous silyl ketene acetal followed by an intramolecular palladium-catalyzed cyclization that proceeds via an enolate arylation.",10.1021/ol1006373,2010-05-06,0.6040039240832199
Synthesis,"A Simple and Practical Approach to the Dibenzo[c,f]thiazolo[3,2-a]azepines: A Novel Fused Tetracyclic Azepine System","A novel set of functionalized dibenzo[c,f]thiazolo[3,2-a]azepines, which is a new ring system, were successfully synthesized in a four-step protocol starting from readily available substituted N-allyl-N-benzylanilines. The synthesis of the title compounds was accomplished through cyclocondensation of morphanthridines with mercaptoacetic acid. Morphanthridines were prepared by selective oxidation of dihydromorphanthridines with pyridinium chlorochromate in dichloromethane. The dihydromorphanthridines were obtained by acid-catalyzed intramolecular Friedel-Crafts alkylation of substituted 2-allyl-N-benzylanilines, which in turn, were prepared from N-allyl-N-benzylanilines by aromatic amino-Claisen rearrangement. The structural elucidation of all synthesized compounds by high resolution NMR is also reported.",10.1055/s-0029-1218674,2010-02-11,0.6039759350837949
Journal of Organic Chemistry,Synthesis of <i>P</i>-Chiral Dihydrobenzooxaphosphole Core for BI Ligands in Asymmetric Transformations,"An efficient and practical synthesis of enantiomerically pure P-chiral dihydrobenzooxaphosphole (BOP) core 1 is developed that is amenable to large scale preparation of the related ligand series. The unique epimerization of the P-chiral center of the undesired (R,R)-diastereomeric phosphine oxide 19 through chlorination followed by crystallization makes this chemical resolution method achieve 65% yield of desired (R,S)-diastereomer 12.",10.1021/acs.joc.7b00491,2017-05-01,0.6039692027827089
Tetrahedron,A selective procedure for α-alkenylation of enones involving Pd-catalyzed alkenyl-alkenyl coupling and its application to a convergent and efficient synthesis of nakienone B,,10.1016/0040-4039(96)00962-8,1996-07-01,0.6039652726747193
Journal of Organic Chemistry,Catalytic Enantioselective Aziridoarylation of Aryl Cinnamyl Ethers toward Synthesis of <i>trans-</i>3-Amino-4-arylchromans,"Catalytic enantioselective one-pot aziridoarylation reaction of aryl cinnamyl ethers has been demonstrated in detail. Combination of suitable copper catalyst and chiral bis-oxazoline ligand was found to be very efficient for asymmetric aziridination followed by intramolecular arylation (Friedel-Crafts) reaction to provide a general and direct method for the synthesis of trans-3-amino-4-arylchromans with high regio-, diastereo- (dr > 99:1), and enantioselectivity (up to 95% ee) with moderate yield. trans-3-Amino-4-arylchroman is an advanced intermediate for the synthesis of chromenoisoquinoline compounds such as doxanthrine, a potent and selective full agonist for the dopamine-D(1) receptor.",10.1021/jo200711s,2011-07-28,0.6039645455846914
Journal of Organic Chemistry,Practical Synthesis of (±)-Chlorovulone II,"We describe a total synthesis of (±)-chlorovulone II that is 10 steps shorter than the best alternative currently available (nine vs 19 steps). The key event of the synthesis is an aldol addition of the enolate of ethyl acetate into 4-cyclopentene-1,3-dione, a substance that has received little attention as an educt for prostanoid synthesis and for which little is known about carbonyl 1,2-addition with enolates. In addition, we provide chemical and stereochemical details of a route to a key intermediate toward the title compound that involves a carbonyl−ene reaction and a radical addition to an aldehyde carbonyl.",10.1021/jo972073f,1998-02-11,0.6039554804437235
Tetrahedron,A novel synthesis of unsymmetrical azo aromatics inaccessible by diazo-coupling reaction,,10.1016/s0040-4039(01)93951-6,1989-01-01,0.6039488142091322
Organic Letters,Catalytic Cyclopropanation of Alkenes Using Diazo Compounds Generated in Situ. A Novel Route to 2-Arylcyclopropylamines,"[reaction: see text]. A user-friendly, one-pot process for catalytic cyclopropanation of alkenes from tosylhydrazones is described. The cyclopropanation of N-vinylphthalimide provides a new route to 2-arylcyclopropylamines, and this is exemplified in the efficient synthesis of the HIV-1 reverse transcriptase inhibitor 6.",10.1021/ol0164177,2001-08-01,0.603946886118111
Journal of the American Chemical Society,Studies Directed toward the Total Synthesis of Cerorubenic Acid-III. 5. A Radical Cyclization Route Leading to the Methyl Ester of the Natural Isomer<sup>1</sup>,"The first total synthesis of cerorubenic acid-III methyl ester is detailed. Enantiopure 4, obtained by anionic oxy-Cope rearrangement of 3, was transformed via diol 11 into lactol 20 . Following proper establishment of both side chains as in 25, a 6-exo radical cyclization was employed to set the configuration of the remaining stereogenic centers. This very useful process set the stage for construction of the pendant side chain. The complete route to 2 from 3-methylcyclohexenone required 30 steps (0.3% overall yield) confirmed the initial complex structural assignment and established the absolute configuration of the natural kairomone.",10.1021/ja980691n,1998-06-01,0.6039449870644961
Synlett,A Convenient Approach to (-)-8-<i>epi</i>-Swainsonine,"A novel and efficient synthesis of (-)-8-epi-swainsonine (2) is reported. Face-selective diol formation from the bicyclic ­alkene 3 followed by a stereoselective vinylation of the aldehyde and ring-closing metathesis gave the indolizidine ring system, which was converted into (-)-8-epi-swainsonine (2).",10.1055/s-2006-939710,2006-05-22,0.6039442740099862
Synthesis,Concise Enantioselective Synthesis of Furan Lignans (-)-Dihydrosesamin and (-)-Acuminatin and Furofuran Lignans (-)-Sesamin and (-)-Methyl Piperitol by Radical Cyclization of Epoxides,"Enantioselective syntheses of furan lignans (-)-dihydrosesamin and (-)-acuminatin and furofuran lignans (-)-sesamin and (-)-methyl piperitol were achieved in up to only three steps in 43%, 42%, 63%, and 60% overall yield, respectively, with high optical purity through stereoselective intramolecular radical cyclization of suitably substituted epoxy olefinic ethers using bis(cyclopentadienyl)titanium(III) chloride as the radical initiator. The key intermediate, chiral epoxy alcohol 4, was prepared by the Sharpless kinetic resolution method. The titanium(III) initiator was prepared in situ from commercially available titanocene dichloride and activated zinc dust in tetrahydrofuran.",10.1055/s-2005-872173,2005-01-01,0.6039402205142237
European Journal of Organic Chemistry,Asymmetric Total Syntheses of Cochliomycin A and Zeaenol,"Abstract The first asymmetric total syntheses of two resorcylic acid lactones (RALs) – cochliomycin A and zeaenol – have been achieved in a divergent way. The main highlight of our strategy involves successful application of stereoselecive Keck allylation and Julia–Kocienski olefination to access an advanced intermediate, by starting from L ‐tartaric acid as a chiral pool compound. This intermediate is coupled with a trisubstituted benzoic acid to afford a common RCM precursor for both target molecules. Ring‐closing metathesis at a late stage, followed by functional group manipulation, yielded the target molecules in an efficient way.",10.1002/ejoc.201200241,2012-06-29,0.6039288546977821
Journal of Organic Chemistry,"A Short Diastereoselective Synthesis of the Putative Alkaloid Jamtine, Using a Tandem Pummerer/Mannich Cyclization Sequence","Treatment of 2-phenylhex-5-enal with benzylamine followed by sequential reaction with ethylthioacetyl chloride and sodium periodate oxidation afforded a E/Z mixture of alpha-sulfinylamides. As anticipated from a 4pi-conrotatory mechanism, cyclization of each olefin afforded fused isoquinoline lactams as single diastereomers epimeric at the ethylthio position without any cross contamination. Some preliminary studies were directed toward the synthesis of mesembrine using a 3,4-dimethoxy aryl group. In this case, the Z-enamide prefers to undergo electrophilic aromatic substitution to give a substituted azepinone as the preferred product in 87% yield. In contrast, the E-enamide isomer provided the desired hydroindolone. The convergency and stereochemical control associated with the tandem Pummerer /Mannich cyclization make it particularly suited for the assembly of jamtine, a tetrahydroisoquinoline alkaloid reputed for its therapeutic properties. The key step in the synthesis involves a domino thionium/N-acyliminium ion cyclization to provide the tricyclic ring skeleton 27a as the major diastereomer. Deprotonation of 27a with NaH gave 28a, which contains the fully assembled skeleton of jamtine. Completion of the synthesis entailed installation of the double bond and reduction of the lactam. Oxidation of a synthetic sample of jamtine with MCPBA afforded the corresponding N-oxide, which does not match the spectral data reported in the literature for this alkaloid. Our synthetic efforts raise the possibility of a revision of the earlier assignment.",10.1021/jo026471g,2003-01-01,0.603919192394846
Organic Process Research & Development,The Synthesis of <i>N</i>-Aryl-5(<i>S</i>)-aminomethyl-2-oxazolidinone Antibacterials and Derivatives in One Step from Aryl Carbamates,"Since 1993, a significant process research and development effort directed towards the large-scale synthesis of oxazolidinone antibacterial agents has been ongoing in both Early Chemical Process Research and Development, and Chemical Process Research and Development at Pharmacia. This work has led to the successful development of the current commercial process to produce Zyvox (linezolid), recently approved by the FDA as an antibacterial. While this synthesis is appropriate for the preparation of linezolid in particular, a more convergent and versatile synthesis was developed for the rapid preparation of numerous other oxazolidinone analogues. Toward this end, economical methods for the large-scale preparation of N -[(2 S )-2-(acetyloxy)-3-chloropropyl]acetamide 3 and tert -butyl [(2 S )-3-chloro-2-hydroxypropyl]carbamate 27 from commercially available ( S )-epichlorohydrin via the common intermediate (2 S )-1-amino-3-chloro-2-propanol hydrochloride 2a were developed. Also, general methods for coupling these reagents with N -aryl carbamates to give N -aryl-5( S )-aminomethyl-2-oxazolidinone derivatives in one step were developed. These reagents and procedures have proven widely applicable in the preparation of a diverse array of oxazolidinone analogues such as 23 and 28 in both process and medicinal chemistry research.",10.1021/op034028h,2003-06-07,0.6038966341139802
Organic Letters,Synthesis of the Sialidase Inhibitor Siastatin B,[structure] The resolved piperidinecarboxylate (R)-7 was converted to siastatin B (1) by an efficient and stereoselective sequence that includes a bromo-beta-lactonization and an N-acyliminium azidation. Two analogues (3 and 4) of siastatin were also prepared.,10.1021/ol0066680,2000-11-17,0.6038932185006585
Journal of Organic Chemistry,Synthesis of Cryptophycins via an<i>N</i>-Acyl-β-lactam Macrolactonization,"An efficient and concise approach to the synthesis of the macrolide core of the cryptophycins has been developed. A novel macrolactonization utilizing a reactive acyl-beta-lactam intermediate incorporates the beta-amino acid moiety within the 16-membered macrolide core. This modular approach, involving a cyanide-initiated acyl-beta-lactam ring opening followed by cyclization, was successfully applied to the total synthesis of cryptophycin-24. The strategy was also used in an efficient synthesis of the 6,6-dimethyl-substituted dechlorocryptophycin-52. In this case, the cyanide-initiated ring opening of the bis-substituted 2-azetidinone followed by macrolactonization was achieved through a catalytic process.",10.1021/jo0302197,2003-11-19,0.603888344679194
Synlett,A Practical Synthesis of 4-Amino-2-(Trifluoromethyl)nicotinic Acid,"A practical synthesis of 4-amino-2-(trifluoromethyl)-nicotinic acid is described. 2-(Trifluoromethyl)pyridine was lithiated using lithium 2,2,6,6-tetramethylpiperidide (LTMP) in the presence of 1,3-dimethyl-2-imidazolidinone (DMI) and followed by CO2 quench to give the C-3 carboxylation product. Subsequent directed C-4 lithiation of carboxylation product afforded 4-iodo-2-(trifluoromethyl)nicotinic acid, which was coupled with tert-butyl carbamate under Pd-catalyzed conditions and followed by Boc deprotection to yield the title product in four steps and 50% overall yield.",10.1055/s-0030-1258481,2010-07-09,0.6038877416170875
Journal of Organic Chemistry,A Novel Approach to the Synthesis of Amino-Sugars. Routes To Selectively Protected 3-Amino-3-deoxy-aldopentoses Based on Pyridinium Salt Photochemistry,"A new approach for the synthesis of selectively blocked 3-amino-3-deoxyaldopentoses is presented. The strategy is based on employment of a pyridinium salt photocyclization-aziridine ring-opening sequence to prepare stereochemically defined, enantiomerically enriched aminocyclopentendiol derivatives. Ring-opening reactions transform these substances into terminally differentiated aminopolyols, which serve as precursors to the target amino-aldopentoses. The utility of this strategy is demonstrated by its application to the syntheses of protected derivatives of D- and L-3-amino-3-deoxyxylose, L-3-amino-3-deoxyarabinose, and a late-stage intermediate in a potential route to N-acetylneuraminic acid.",10.1021/jo020038p,2002-04-17,0.6038823201623303
Tetrahedron,"Total synthesis of 15(RS)-5,6-dehydro-8-epi-PGF2α methyl ester by a biomimetic process",,10.1016/s0040-4039(97)00100-7,1997-03-01,0.6038703291504477
Organic Process Research & Development,"Axial Chirality in the Sotorasib Drug Substance, Part 1: Development of a Classical Resolution to Prepare an Atropisomerically Pure Sotorasib Intermediate","Described herein is the discovery and development of a process to prepare an atropisomeric intermediate in the synthesis of the KRAS G12C inhibitor sotorasib. Using high-throughput experimentation, (+)-2,3-dibenzoyl- d -tartaric acid [(+)-DBTA] was identified as an inexpensive and readily available resolving agent that enables separation and isolation of the desired atropisomer through a classical resolution. Subsequent optimization and characterization studies led to a highly selective process, providing the desired atropisomer as a unique three-component cocrystal solvate with a selectivity of >2000:1. This classical resolution has been performed successfully on >500 kg scale and was critical to the commercialization of the sotorasib manufacturing process.",10.1021/acs.oprd.2c00176,2022-08-23,0.6038658365944751
Synthesis,Concise Synthesis of (S)-7-Hydroxy-5-aza-8a-epi-d-swainsonine from a d-Erythrose Derivative,"Abstract A five-step synthesis of (S)-7-hydroxy-5-aza-8a-epi-d-swainsonine [(3S,4S,4aS,5S,6R)-octahydropyrrolo[1,2-b]pyridazine-3,4,5,6-tetraol] was accessed in good overall yield from readily available d-erythrosyl benzylidene acetal buta-1,3-diene. The key step of the reaction sequence is a full stereoselective Diels–Alder cycloaddition between­ the diene and dienophile: diethyl azodicarboxylate (DEAD) or di-tert-butyl azodicarboxylate (DBAD). The cycloadducts were further transformed into the title 5-aza-indolizidine. Optimized procedures were obtained for the synthesis of intermediates and products.",10.1055/a-1768-2082,2022-02-10,0.6038656893279771
Synthesis,"A Convenient and Efficient Synthesis of Polyphenylmono-, di-, and -triaminobenzenes","All articles of this category A new convenient and efficient synthesis of polyphenylmono- and -diaminobenzenes by the palladium(0)-catalyzed cross-coupling reaction of polyhalomono- and -diaminobenzenes with phenylboronic acid is described. A synthesis of 2,4-diphenyl-1,3,5-triaminobenzene is also reported. Pd-catalyzed cross coupling - phenylation - phenylboronic acid - polyhalomono- and -diaminobenzenes - polyphenylmono-, -di-, and -triaminobenzenes",10.1055/s-1995-4113,1995-11-01,0.6038485051679784
Tetrahedron,Palladium-catalyzed one-pot Suzuki coupling followed by arylpalladium addition to aldehyde: a convenient route to fluoren-9-one derivatives,,10.1016/j.tetlet.2010.08.062,2010-08-22,0.6038414283754331
Journal of Organic Chemistry,Synthesis of Sphingomyelin Carbon Analogues as Sphingomyelinase Inhibitors,"The highly efficient and stereocontrolled syntheses of sphingomyelin carbon analogues 1 and 2 were achieved by effectively utilizing Hofmann rearrangement of enantiomerically pure beta-hydroxyamide 7, which was prepared by an asymmetric hydrogenation of alpha-acyl-gamma-butyrolactone 9 and ring opening with NH(3). Intermediary isocyanate 6 was selectively trapped with the vicinal hydroxy group in an intramolecular fashion to produce an oxazolidinone derivative, 5. In the synthesis of a quite polar compound such as 1, a convenient one-pot procedure of the introduction of a benzyloxycarbonyl group into the hydroxy group resulting from the oxazolidinone ring opening is another key point, because, in addition to the efficiency, this protecting group was easily removable by a simple procedure and workup at the final step. Both synthesized compounds 1 and 2 showed moderate inhibitory activity toward sphingomyelinase from B. cereus.",10.1021/jo025529o,2002-05-31,0.6038341581340935
Journal of Organic Chemistry,A Highly Enantioselective Benzothiepine Synthesis,"A highly enantioselective synthesis of benzothiepine 1a has been accomplished via an enantioenriched sulfoxide intermediate obtained by asymmetric oxidation with a chiral oxaziridine in 89:11 er. The key step is a thermodynamically controlled asymmetric cyclization reaction that produces two new stereogenic centers. The (4R,5R) isomer 1a was obtained in 98:2 er.",10.1021/jo991786q,2000-04-08,0.6038296889984851
Synthesis,Total Synthesis of the Biphenomycins; III<sup>1</sup>.1 Synthesis of Biphenomycin B,"(opens in new window) Buy Article (opens in new window) Permissions and Reprints (opens in new window) All articles of this category (opens in new window) The total synthesis of the cyclopeptide biphenomycin B (1b) , a compound exhibiting a potent antibacterial activity against Gram-positive bacteria, is described. The non-proteinogenic amino acid ( S,S )-diisotyrosine (2) was prepared by enantioselective hydrogenation of the corresponding didehydroamino acids. The 15-membered ansa ring was obtained in 85% yield within 5 minutes by ring closure of the appropriate linear pentafluorophenyl ester in the two phase system chloroform-aqueous sodium hydrogen carbonate without dilution.",10.1055/s-1992-26293,1992-01-01,0.6038241637372873
Organic Letters,Synthesis of Polyene Bioactive Natural Products: FR252921 and Vitamin A,"A formal synthesis of FR252921, a potent macrocyclic immunosuppressive agent, and a six-step synthesis of vitamin A have been demonstrated. The application of a ruthenium-catalyzed step-economic and environmentally benign strategy for the highly stereo- and chemoselective construction of valuable polyene motifs of FR252921 and vitamin A highlights the syntheses. The key features for the synthesis FR252921 include preparation of the triene moiety followed by two consecutive peptide couplings of the three fragments.",10.1021/acs.orglett.2c00546,2022-03-11,0.6038126494281972
Tetrahedron,Enantioselective synthesis of planar chiral azaferrocenes via chiral ligand-mediated ring- and lateral-lithiations,,10.1016/j.tetlet.2003.08.010,2003-09-01,0.6038105221062833
Tetrahedron,An efficient synthesis of 3′-fluoro-3′-deoxythymidene (FLT),,10.1016/s0040-4039(00)60841-9,1992-11-01,0.603809986020672
European Journal of Organic Chemistry,Synthesis of (<i>R</i>)‐(–)‐2‐Fluoronorapomorphine — A Precursor for the Synthesis of (<i>R</i>)‐(–)‐2‐Fluoro‐<i>N</i>‐[<sup>11</sup>C]propylnorapomorphine for Evaluation as a Dopamine D<sub>2</sub> Agonist Ligand for PET Investigations,"Abstract 2‐Fluoronorapomorphine, the PET labelling precursor to 2‐fluoro‐ N ‐[ 11 C]propylnorapomorphine, was prepared in 13 steps from codeine in a total yield of 10 %. Codeine was converted in four steps into N ‐benzylnorcodeine which was oxidised by using the Swern protocol. Subsequent acid‐catalysed rearrangement afforded N ‐benzylnormorphothebaine which was selectively triflylated at the 2‐position and pivaloylated at the 11‐position. The triflate underwent palladium‐catalysed amination with benzophenone imine. Amination conditions required sequential base addition to give substantial conversion of the triflate to the corresponding N ‐substituted benzophenone imine. After acidic hydrolysis the resulting aniline was transformed into the 2‐fluoro compound via the Balz–Schiemann reaction. Hydrogenolysis of the N ‐benzyl group followed by deprotection of the catechol moiety using BBr 3 provided 2‐fluoronorapomorphine. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2005)",10.1002/ejoc.200500295,2005-09-07,0.6038089032258961
Tetrahedron,"Alkoxy base-mediated selective synthesis and new rearrangements of 1,2,4-triazolodipyrimidinones",,10.1016/j.tetlet.2017.01.030,2017-01-11,0.6038024797170334
Synthesis,Biomimetic Synthesis of Ascididemin and Derivatives,"All articles of this category A two-step biomimetic synthesis of the pentacyclic pyrido[2,3,4- kl acridine marine alkaloid ascididemin ( 3a ) from quinolinequinone 5a and N -trifluoroacetamidokynuramine ( 4 ) is described. The crucial step ( 6 to 7 ) involves the simultaneous formation of two pyridine rings in a process which might well offer an explanation for the biogenetic synthesis in marine organisms. The preparation of substituted ascididemins by either starting from substituted quinoline-quinones, e.g., 5b to afford 11-methoxyascididemin ( 3b ), or by nitration of 3a to the mono 1- or 3-nitroascididemins ( 8 and 9 respectively) is reported.",10.1055/s-1994-25446,1994-01-01,0.6037962428549685
Angewandte Chemie International Edition,Stereoselective Total Synthesis of (−)‐Borrelidin,A convergent synthesis of (−)-borrelidin (1) is reported based on the retrosynthetic disconnections indicated in the picture. Highlights of the strategy include the construction of a strained enynone-containing macrolide and the installation of a cyano group in a regioselective manner by a novel molybdenum-catalyzed hydrostannation of the alkyne.,10.1002/anie.200460203,2004-07-20,0.6037920379899437
Tetrahedron,Asymmetric synthesis. XXXI. Synthesis of 2-substituted piperazines from chiral non-racemic lactams,,10.1016/s0040-4039(00)77163-2,1994-04-01,0.6037876315793339
Tetrahedron,Asymmetric synthesis. XXX. Synthesis of 3-substituted piperidines from chiral non-racemic lactams,,10.1016/s0040-4039(00)77162-0,1994-04-01,0.6037876315793339
European Journal of Organic Chemistry,Synthesis of (±)‐β‐Allokainic Acid,"The total synthesis of kainoid alkaloid, (+/–)‐β‐allokainic acid is reported. The key step is a vinylogous Cloke–Wilson rearrangement followed by Lewis acid and transition metal induced transformations to prepare a highly functionalized pyrrolidine suitable for conversion to the target molecule.",10.1002/ejoc.201900368,2019-05-22,0.603783261543614
Journal of Organic Chemistry,Total Synthesis of Rutamycin B and Oligomycin C,"The asymmetric synthesis of the macrolide antibiotics (+)-rutamycin B (1) and (+)-oligomycin C (2) is described. The approach relied on the synthesis and coupling of the individual spiroketal fragments 3a and 3b with the C1-C17 polyproprionate fragment 4. The preparation of the spiroketal fragments was achieved using chiral (E)-crotylsilane bond construction methodology, which allowed the introduction of the stereogenic centers prior to spiroketalization. The present work details the synthesis of the C19-C28 and C29-C34 subunits as well as their convergent assembly through an alkylation reaction of the lithiated N,N-dimethylhydrazones 6 and 8 to afford the individual linear spiroketal intermediates 5a and 5b, respectively. After functional group adjustment, these advanced intermediates were cyclized to their respective spiroketal-coupling partners 40 and 41. The requisite polypropionate fragment was assembled in a convergent manner using asymmetric crotylation methodology for the introduction of six of the nine-stereogenic centers. The use of three consecutive crotylation reactions was used for the construction of the C3-C12 subunit 32. A Mukaiyama-type aldol reaction of 35 with the chiral alpha-methyl aldehyde 39 was used for the introduction of the C12-C13 stereocenters. This anti aldol finished the construction of the C3-C17 advanced intermediate 36. A two-carbon homologation completed the construction of the polypropionate fragment 38. The completion of the synthesis of the two macrolide antibiotics was accomplished by the union of two principal fragments that was achieved with an intermolecular palladium-(0) catalyzed cross-coupling reaction between the terminal vinylstannanes of the individual spiroketals 3a and 3b and the polypropionate fragment 4. The individual carboxylic acids 46 and 47 were cyclized to their respective macrocyclic lactones 48 and 49 under Yamaguchi reaction conditions. Deprotection of these macrolides completed the synthesis of the rutamycin B and oligomycin C.",10.1021/jo001767c,2001-03-23,0.6037631023371858
Journal of Organic Chemistry,Enantioselective Total Synthesis of Lycoposerramine-Z Using Chiral Phosphoric Acid Catalyzed Intramolecular Michael Addition,"A new enantioselective total synthesis of phlegmarine-type Lycopodium alkaloid lycoposerramine-Z (1) has been accomplished, using one-pot chemoselective sequential additions of two different Grignard reagents to the bis-Weinreb-amide intermediate and an efficient construction of the fully fuctionalized cyclohexanone intermediate with a chiral phosphoric acid catalyzed enantioselective intramolecular Michael addition.",10.1021/acs.joc.5b02723,2016-02-12,0.6037620286312774
Journal of Organic Chemistry,"Asymmetric Total Synthesis of 4-Hydroxy-8-<i>O</i>-methyltetrangomycin, 4-Hydroxytetrangomycin, and 4-Keto-8-<i>O</i>-methyltetrangomycin","Herein, we report the first asymmetric total synthesis of 4-hydroxy-8- O -methyltetrangomycin ( 1 ), 4-hydroxytetrangomycin ( 2 ), and 4-keto-8- O -methyltetrangomycin ( 3 ), angucyclinones featuring a highly oxidized nonaromatic A ring. A sequential enyne metathesis/Diels–Alder approach was utilized successfully to construct the tetracyclic skeleton of the angucyclinones. Late-stage acetonide deprotection challenges were overcome by A ring functional group manipulation, yielding a dihydroxy intermediate prior to the benzylic photo-oxidation, facilitating the total syntheses of angucyclinones 1 – 3 . The key stereocenter was established through a known Sharpless asymmetric epoxidation/regioselective epoxide opening reaction.",10.1021/acs.joc.4c01393,2024-07-22,0.6037574915909418
European Journal of Organic Chemistry,Synthesis of Raputimonoindoles A–C and Congeners,"The first synthesis of raputimonoindole A from the tree Raputia praetermissa (Rutaceae) is reported, starting from indole‐5‐carbaldehyde. The key step is Braun′s diastereoselective Heck–Suzuki cascade that assembled the prenylated methylenetetrahydrofuran moiety. The unsubstituted indole enamine functionality was tolerated, and the absolute configuration of naturally occurring raputimonoindole A is assigned as ( R , R ). Raputimonoindole B was accessed by Ir‐catalyzed C–H activation/borylation followed by Suzuki–Miyaura cross‐coupling. Two biosynthetically related 5‐(dihydrofuran‐2‐yl)indole derivatives from R. simulans were synthesized by ring‐closing metathesis, and their absolute configurations were determined.",10.1002/ejoc.201900583,2019-05-09,0.6037551172285681
Synthesis,Development of New Chiral AuxiliaryDerived from (<i>S</i>)-(-)-Phenylethylamine fora Synthesis of Enantiopure (<i>R</i>)-2-PropyloctanoicAcid,"A new chiral auxiliary, {[(1S)-1-phenylethyl]amino}phenol, derived from (S)-(-)-1-phenylethylamine was developed for asymmetric synthesis of (R)-2-propyloctanoic acid (1) with moderate diastereoselectivity and good crystalline property.",10.1055/s-2003-39394,2003-01-01,0.6037445913608431
Synthesis,"Synthesis of the Bifunctional Chelating Agent 6-(4-Aminobenzyl)-1,4,8,11-tetra-azacyclotetradecan-N,N',N'',N'''-tetraacetic Acid (H2NBn-TETA)","All articles of this category An improved, five-step synthesis (7% overall yield) of 6-(4-aminobenzyl)-1,4,8,11-tetraazacyclotetradecane- N,N',N'',N''' -tetraacetic acid (H 2 NBn-TETA, 6 ), an azamacrocyclic ligand used as a radionuclide carrier in cancer chemotherapy, is reported and its complete characterization and purification is for the first time described. azamacrocycles",10.1055/s-1997-1314,1997-09-01,0.603736418855679
Organic Process Research & Development,Leveraging Synergistic Solubility in the Development of a Direct Isolation Process for Nemtabrutinib,"We report the process development for the active pharmaceutical ingredient (API) step of the commercial manufacturing route to nemtabrutinib (MK-1026), a reversible Bruton’s Tyrosine Kinase (BTK) inhibitor currently under investigation for the treatment of several hematological malignancies. Significant improvements on process efficiency were achieved by a direct isolation process leveraging optimal reaction conditions and synergistic API solubility in an ethanol/water system. In combination with additional robustness improvements on impurity control, an efficient, practical, and scalable synthesis of nemtabrutinib was developed.",10.1021/acs.oprd.2c00391,2023-03-10,0.6037342163638161
Synlett,Regioselective <i>O</i>-Alkylation of Ascorbic Acid for the Efficient Synthesis of Lipophilic Antioxidants,,10.1055/s-1999-2522,1999-01-01,0.6037324263168246
Synthesis,Stereoselective Synthesis of a Mevinic Acid Analogue,"An efficient and versatile synthetic method for the stereoselective synthesis of a mevinic acid analogue is described. This approach uses a combination of a Cosford protocol with a catecholborane-mediated stereoselective reduction of acyclic β-hydroxy ketones to syn-1,3-diols, as key steps.",10.1055/s-2007-965904,2007-02-22,0.6037293778895392
Organic Process Research & Development,Route Optimization and Synthesis of Taxadienone,"Early process development toward the scalable production of taxadienone on a decagram scale is described. A continuous flow reactor was employed to safely run a potentially hazardous cyclopropane ring opening. The route featured two copper-mediated additions, a Diels–Alder reaction and a palladium-catalyzed Negishi coupling, to construct the final structure.",10.1021/op500314c,2014-12-15,0.6037219475298037
Organic Letters,Total Synthesis of (+)-Jatrophalactam,"The first asymmetric total synthesis of (+)-jatrophalactam was reported, which unambiguously determined the absolute configuration of the titled natural product. The key features entail a conformationally controlled cyclopropanation, a Meldrum's acid adduct-engaged macrolactam formation, and a Pd(II)-mediated oxidative cyclization.",10.1021/acs.orglett.9b03778,2019-11-07,0.6037095821330729
Journal of Organic Chemistry,"Toward the Asymmetric de Novo Synthesis of Lanostanes: Construction of 7,11-Dideoxy-Δ<sup>5</sup>-lucidadone H","Efforts to establish an asymmetric entry to hexanorlanostanes has resulted in a concise synthesis of 7,11-dideoxy-Δ 5 -lucidadone H from epichlorohydrin. By exploiting metallacycle-mediated annulative cross-coupling (to establish a functionalized hydrindane) and stereoselective formation of the steroidal C9–C10 bond to establish a stereodefined 9-alkyl estrane, 14 subsequent steps have been established to generate a hexanorlanostane system. Key transformations include formal inversion of the C13 quaternary center, oxidative dearomatization/group-selective Wagner–Meerwein rearrangement, and Lewis acid mediated semi-Pinacol rearrangement.",10.1021/acs.joc.2c02042,2022-10-07,0.603694698990925
Organic Letters,"Total Syntheses of Festuclavine, Pyroclavine, Costaclavine, <i>epi</i>-Costaclavine, Pibocin A, 9-Deacetoxyfumigaclavine C, Fumigaclavine G, and Dihydrosetoclavine","A new approach for the divergent total synthesis of eight ergot alkaloids is reported. The approach allows the first total syntheses of pyroclavine, pibocin A, 9-deacetoxyfumigaclavine C, and fumigaclavine G and also enables the efficient synthesis of festuclavine, costaclavine, epi-costaclavine, and dihydrosetoclavine. The main feature of the synthesis is the use of an unprecedented Pd-catalyzed intramolecular Larock indole annulation/Tsuji-Trost allylation cascade to assemble the tetracyclic core in one step.",10.1021/acs.orglett.7b01504,2017-06-08,0.6036895643814858
Tetrahedron,Chiral synthesis of thromboxane B2 intermediates,,10.1016/s0040-4039(01)85087-5,1978-01-01,0.6036879391832888
Organic Process Research & Development,Stereoselective Lithiation and Carboxylation of Boc-Protected Bicyclopyrrolidine: Synthesis of a Key Building Block for HCV Protease Inhibitor Telaprevir,"A stereoselective process for the manufacture of bicyclopyrrolidine 7 to 2 has been developed. The process utilizes a stereoselective lithiation/carboxylation sequence. The achiral diamine ligand DPBP induces excellent diastereocontrol, and resolution with ( S )-THNA provides the corresponding salt of 8 in high er and dr. Subsequent processing of 8 gives 2 as the oxalate salt in an overall yield of 27% from 7 (based on total molar charge of 7 ). Compound 2 was obtained with high chemical and chiral purities. The process was successfully demonstrated on >100 kg scale.",10.1021/op500040j,2014-05-05,0.6036838596185597
Tetrahedron,Synthesis of alditols by reductive radical fragmentation of N-phthalimido glycosides. Preparation of chiral synthetic intermediates,,10.1016/s0040-4039(99)01482-3,1999-10-01,0.6036684578542253
European Journal of Organic Chemistry,A Divergent Enantioselective Synthesis of 9‐J<sub>1</sub>‐Phytoprostane and 9‐A<sub>1</sub>‐Phytoprostane Methyl Ester,"Abstract The first syntheses of 9‐J 1 ‐phytoprostane and 9‐A 1 ‐phytoprostane methyl ester were achieved enantioselectively using a divergent approach from a common intermediate sulfone 4 . The divergence was accomplished using a sigmatropic rearrangement (swap protocol) to give sulfone 5 in 47 % overall yield. The two upper side‐chains, with a stereodefined E double bond, were installed using consolidated Julia–Lythgoe olefination reactions of sulfones 4 and 5 , with the same enantiopure α‐protected aldehyde 6 .",10.1002/ejoc.201301703,2014-01-29,0.6036659183455219
Journal of Organic Chemistry,Selective Synthesis of Multisubstituted Olefins Utilizing <i>gem</i>- and <i>vic</i>-Diborylated Vinylsilanes Prepared by Silylborylation of an Alkynylboronate and Diborylation of Alkynylsilanes,"The synthesis of a series of gem- and vic-diborylated vinylsilanes was accomplished via highly selective transition-metal-catalyzed syn-dimetalation to the alkynylmetal species. This protocol served as a general synthetic method toward regio- and stereodefined multisubstituted olefins. The key steps are the diastereoselective Suzuki-Miyaura cross-coupling reactions of gem- and vic-diborylated vinylsilanes, in which the two boron groups showed discrete reactivities to afford diverse precursors of multisubstituted olefins.",10.1021/jo4024057,2013-12-09,0.6036606908277661
Organic Process Research & Development,Development of Scalable Synthesis of RAS Inhibitor’s Indole Building Block via Flow Chemistry,"Using flow chemistry, two scalable synthetic routes were developed for the indole building block [5-bromo-3-(3-(( tert -butyldiphenylsilyl)oxy)-2,2-dimethylpropyl)-2-iodo-1 H -indole], a key intermediate in RAS inhibitors. This approach overcomes limitations of existing literature and patented procedures, which often involve repeated column chromatography purification, low overall yields, the handling of unstable intermediates, challenges in reaction monitoring, and potential safety risks.",10.1021/acs.oprd.5c00350,2025-12-22,0.6036549915034332
Synthesis,"Synthesis of Selenated Unsymmetrical Analogs of BEDT-TTF, BEDO-TTF and DMET","All articles of this category An improved synthesis of EDSEDT-TTF 4 and EDSEDO-TTF 5 from appropriate cross-coupling reactions involving 4,5-bis(2-cyanoethylthio)-1,3-dithiol-2-one (9) and 4,5-bis(2-cyanoethylseleno)-1,3-dithiol-2-one (11) as key intermediates is described. Moreover, a Wittig-type preparation of new selenated derivatives 6 and 7 of DMET molecule from the useful new precursor [4,5-bis(2-cyaoethylseleno)-1,3-dithiol-2-yl]triphenylphosphonium tetrafluoroborate (17) is presented. selenated analogs of BEDT-TTF and DMET - cross coupling reaction - pseudo Wittig condensation - cyanoethyl groups",10.1055/s-1997-1494,1997-01-01,0.6036470651329123
Organic Process Research & Development,"Development and Pilot-Scale Demonstration of a Process for Inhibitors of the HIV Nucleocapsid Protein, NCp7","A manufacturing process to prepare two antiretroviral agents that denature the HIV-1 nucleocapsid protein (NCp7) has been developed and demonstrated on a pilot scale. 2,2‘-Dithiobis(benzoyl chloride) (4), prepared from commercially available 2,2‘-dithiobis(benzoic acid) (3), was coupled directly with l -isoleucine to give the potential anti-HIV compound [ S -( R *, R *)]-2-{[2-[[2-[(1-carboxy-2-methylbutyl)carbamoyl]phenyl]dithio]benzoyl]amino}-3-methylpentanoic acid (2) thereby eliminating the α-amino acid protection and deprotection steps used in the original synthesis. Compound 2 was oxidized by bromine to a second potential anti-HIV compound [ S -( R *, R *)]-3-methyl-2-(3-oxo-3 H -benzo[ d ]isothiazol-2-yl)pentanoic acid (1). The intermediacy of the hydrobromide salt of 1 provided an effective purity control in the production of the pharmaceutical agent. Cost, operational, safety, environmental, and equipment considerations were taken into account during the course of development.",10.1021/op9701191,1998-03-12,0.603640837377295
Journal of the American Chemical Society,Total Synthesis of (−)-Kendomycin Exploiting a Petasis−Ferrier Rearrangement/Ring-Closing Olefin Metathesis Synthetic Strategy,"The total synthesis of (-)-kendomycin (1), a novel macrocyclic polyketide with antibacterial and antitumor activity, was achieved in 21 steps (longest linear sequence) exploiting an effective Petasis-Ferrier union/rearrangement tactic to construct the tetrahydropyran ring, a ring-closing metathesis to generate the macrocycle, and a biomimetic quinone-methide-lactol assembly.",10.1021/ja051420x,2005-04-23,0.6036390040561277
Organic Letters,Enantioselective Synthesis of 4′-Ethynyl-2-fluoro-2′-deoxyadenosine (EFdA) via Enzymatic Desymmetrization,"An enantioselective synthesis of the potent anti-HIV nucleoside EFdA is presented. Key features of stereocontrol include construction of the fully substituted 4'-carbon via a biocatalytic desymmetrization of 2-hydroxy-2-((triisopropylsilyl)ethynyl)propane-1,3-diyl diacetate and a Noyori-type asymmetric transfer hydrogenation to control the stereochemistry of the 3'-hydroxyl bearing carbon. The discovery of a selective crystallization of an N-silyl nucleoside intermediate enabled isolation of the desired β-anomer from the glycosylation step.",10.1021/acs.orglett.7b00091,2017-02-06,0.6036383949353393
Tetrahedron,Palladium-assisted route to carbocyclic nucleosides: A formal synthesis of (±)-aristeromycin,,10.1016/s0040-4039(00)70635-6,1989-01-01,0.6036358212165039
Synthesis,"Concise Syntheses of α-Galactosyl Ceramide, d-ribo-Phytosphingosine, and Ceramide","Total syntheses of α-galactosyl ceramide, d - ribo -phytosphingosine, and ceramide through an α-galactosyl phytosphingosine derivative as a common synthon were accomplished in overall yields of 26%, 15%, and 20% in nine, seven, and eight steps, respectively, starting from an acetonide-protected d -lyxose derivative. This short and efficient protocol involved protection and glycosylation of the acetonide-protected d -lyxose with d -galactosyl iodide as a key step. The resulting α-linked disaccharide was subsequently transformed into α-galactosyl ceramide, phytosphingosine, and ceramide.",10.1055/s-0032-1317985,2013-01-08,0.6036204010880486
Synthesis,A Facile Total Synthesis of (±)-Cembrene by Titanium-Induced Keto Ester Cyclization,"All articles of this category A direct approach of titanium-induced intramolecular keto ester cyclization was applied to the total synthesis of macrocyclic diterpenoids, by which (±)-cembrene was synthesized from geranylacetone by a short and efficient route.",10.1055/s-1994-25543,1994-01-01,0.6036185740893412
Organic Process Research & Development,"Toward a Practical, Two-Step Process for Molnupiravir: Direct Hydroxamination of Cytidine Followed by Selective Esterification","A two-step synthesis of molnupiravir ( 1 ) is presented. This work focuses on the development of practical reaction and purification conditions toward a manufacturing route. The sequence commences from highly available cytidine ( 2 ), and molnupiravir is formed through direct hydroxamination of the cytosine ring and esterification of the sugar’s primary alcohol without use of protecting or activating groups. A highly crystalline hydrate of N -hydroxycytidine ( 3 ) resulted in an easily purified intermediate, and a practical, off-the-shelf enzyme was selected for the acylation. The yield was increased through a chemically promoted, selective ester cleavage, which converted a byproduct, molnupiravir isobutyryl oxime ester ( 4 ), into the final API. Both reactions proceed in >90% assay yield, and crystallization procedures are used to afford intermediates and active pharmaceutical ingredients in purities above 99% with an overall yield of 60%. Excellent throughput and sustainability are achieved by limiting the total concentration to 7 volumes of solvent in the course of the two reactions with an overall PMI of 26 including work-up and isolation. Environmentally friendly solvents, water and 2-methyl tetrahydrofuran, enhance sustainability of the operation.",10.1021/acs.oprd.1c00033,2021-07-28,0.6036178751696359
Tetrahedron,An efficient metal-free synthesis of 2-(pyrazin-2-yl)benzimidazoles from quinoxalinones and diaminomaleonitrile via a novel rearrangement,,10.1016/j.tetlet.2011.11.013,2011-11-16,0.6036097335706813
Journal of the American Chemical Society,Total Synthesis of HUN-7293,"The first total synthesis of the cyclic heptadepsipeptide HUN-7293 ( 1 ), a potent inhibitor of cell adhesion molecule expression exhibiting anti-inflammatory properties, is detailed. The most effective approach relied on an unusually efficient macrocyclization with the formation of the MLEU 3 −LEU 4 secondary amide that potentially benefits from intramolecular H-bonding preorganization of the acyclic substrate. The requisite linear depsipeptide was convergently assembled with the late stage introduction of the linking ester enlisting a Mitsunobu esterification that occurs with inversion of the DGCN α-center permitting the utilization of a readily available l -amino acid precursor to the d α-hydroxy carboxylic acid residue. An alternative and similarly attractive approach of direct macrolactonization of a substrate necessarily incorporating a d -DGCN subunit proved viable albeit less effective. Biological evaluation in cellular assays for vascular adhesion molecule expression confirmed that synthetic HUN-7923 ( 1 ) is essentially indistinguishable from the naturally occurring cyclodepsipeptide.",10.1021/ja990918u,1999-06-19,0.6036091597912886
Journal of Organic Chemistry,Synthesis of (+)-Hypoxylactone through Allenoate γ-Addition: Revision of Stereochemistry,"A synthesis of (+)-hypoxylactone has been accomplished in four steps starting from the allenoate γ-addition of threo -3-chloro-2-silyoxybutanals, leading to the revision of stereochemistry. The key was the discovery of control elements required to matching/mismatching cases in the allenoate γ-addition to provide the desired adducts as a single isomer. The utility of the γ-adduct was demonstrated with the Au(I)-catalyzed cyclization to afford (+)-xylogiblactone A. Use of Ag 2 O was the key to epoxidation for preventing epimerization of the γ-lactone ring.",10.1021/acs.joc.0c02194,2020-10-28,0.6036081544760584
Angewandte Chemie International Edition,Synthesis of Amathaspiramides by Aminocyanation of Enoates,"Concise routes for the total and formal syntheses of the amathaspiramides were developed through a formal [3+2] cycloaddition between lithium(trimethylsilyl)diazomethane and α,β-unsaturated esters. The effectiveness of this new cycloaddition for the construction of Δ(2)-pyrazolines containing a α-tert-alkylamino carbon center and subsequent facile protonolytic N-N bond cleavage allows the synthesis of a key intermediate of the amathaspiramides and other α,α-disubstituted amino acid derivatives.",10.1002/anie.201503982,2015-06-30,0.6036039793706987
Synthesis,"Alkyl Nitrites: Novel Reagents for One-Pot Synthesis of 3,5-Disubstituted Isoxazoles from Aldoximes and Alkynes","An efficient, one-pot approach has been described for the synthesis of 3,5-disubstituted isoxazoles from substituted aldoximes (mixture of E and Z ) and alkynes, using alkyl nitrites under conventional heating conditions. The key nitrile oxide intermediates that are required for the synthesis of isoxazoles are formed by treatment of substituted aldoxime with either tert -butyl nitrite or isoamyl nitrite. The generated nitrile oxides underwent in situ [3+2] dipolar cycloaddition to the substituted alkynes to give 3,5-disubstituted isoxazoles regioselectively in high to excellent yields. The developed synthetic methodology was applied for the synthesis of a previously reported potent hDGAT1 inhibitor.",10.1055/s-0035-1561464,2016-06-22,0.6036023981558729
Tetrahedron,"Synthesis of 6-C-(3,3-dimethyl-2-propen-1-yl) norwogonin",,10.1016/s0040-4039(00)60856-0,1992-11-01,0.6036020327748306
Synlett,Synthesis of Arylethyl (E)-Styrylsulfones and Arylsulfones by One-Pot DIBAL-H/NaH-Mediated Reaction of β-Ketosulfones,A facile one-pot synthetic route for preparing a series of arylethyl ( E )-styrylsulfones or arylethyl arylsulfones is developed. The efficient one-pot DIBAL-H/NaH-mediated route includes reduction of α-benzyl-β-arylketosulfones and retroaldol/aldol or retro­aldol reaction of the resulting intermediate. The DIBAL-H/NaH-mediated reaction mechanism has been discussed.,10.1055/s-0033-1339117,2014-06-02,0.6035961014108382
Tetrahedron,A new asymmetric route to synthetically useful γ-substituted γ-butyrolactones,,10.1016/s0040-4039(00)00538-4,2000-05-01,0.6035958208070014
Tetrahedron,Regiocontrolled synthesis of highly-functionalized fused imidazoles: a novel synthesis of second generation LFA-1 inhibitors,,10.1016/s0040-4039(03)01535-1,2003-08-01,0.6035869487616978
Journal of the American Chemical Society,Concise Total Synthesis of the Potent Translation and Cell Migration Inhibitor Lactimidomycin,"An efficient total synthesis of the antiproliferative macrolide and cell migration inhibitor lactimidomycin (3) is reported, which relies on the performance of ring closing alkyne metathesis (RCAM). The strained 12-membered 1,3-enyne 21 as the key intermediate was forged with the aid of [(Ph(3)SiO)(3)Mo≡CPh]·OEt(2) (27) as the most effective member of a new generation of powerful alkyne metathesis catalysts. 21 was elaborated to the target by a ruthenium catalyzed trans-hydrosilylation/proto-desilylation sequence and a highly diastereoselective Mukaiyama aldol reaction controlled by oxazaborolidinone 29 as strategic operations.",10.1021/ja107141p,2010-09-10,0.6035846734830546
Angewandte Chemie International Edition,Concise Enantioselective Total Syntheses of Rearranged <i>ent</i> ‐Trachylobane Diterpenoids (–)‐Wallichanols A and B,"Abstract Herein, we report the first enantioselective total syntheses of three rearranged ent ‐trachylobane diterpenoids, (–)‐Wallichanol A ( 1 ), (–)‐Wallichanol B ( 2 ), and (–)‐Sanguinolane ( 3 ), using a 13, 17, and 14 step longest‐linear sequences respectively, featuring a novel intramolecular [2 + 2] cycloaddition to construct the unique pentacyclic framework containing an unprecedented tricyclo[3.3.1.0 2,7 ]nonane motif. Other key steps in the synthetic route include a highly challenging, selective alkene reduction via hydrogen atom transfer (HAT), leveraging the thermodynamic preference for a tertiary carbon‐centered radical; a Robinson‐type annulation to construct the tricyclic terpenoid building block; and applying aerobic oxidation at two distinct points to form α ‐hydroxy ketones, facilitating the enantioselective syntheses of these diterpenoids.",10.1002/anie.202505766,2025-04-22,0.6035752669197261
Tetrahedron,"Total Synthesis of A Putative Triene Intermediate in Monensin Biosynthesis, Activated as a Caprylcysteamine Thiol Ester.",,10.1016/s0040-4039(00)82346-1,1988-01-01,0.6035717369868481
Journal of the American Chemical Society,"Structure Assignment, Total Synthesis, and Antiviral Evaluation of Cycloviracin B<sub>1</sub>","The first total synthesis of the antivirally active glycolipid cycloviracin B(1) (1) is described. The approach is based on a two-directional synthesis strategy which constructs the C(2)()-symmetrical macrodiolide core of the target by an efficient template-directed macrodilactonization reaction promoted by 2-chloro-1,3-dimethylimidazolinium chloride 14 as the activating agent. Attachment of the lateral fatty acid chains to the lactide core thus formed features not only one of the most advanced ligand-controlled addition reactions of a functionalized dialkyl zinc reagent to a polyfunctional aldehyde, but also a highly demanding Julia-Kocienski olefination of a tetrazolyl sulfone bearing electrophilic and base-labile beta-hydroxy ester motifs. By virtue of the flexibility of this synthesis plan, it was possible to prepare a series of macrodiolide cores differing only in the absolute stereochemistry at the branching points as well as a host of model compounds for the fatty acid appendices of cycloviracin. Comparison of these derivatives with the natural product allowed us to establish the as yet unknown absolute stereochemistry of 6 chiral centers of 1 as (3R,19S,25R,3'R,17'S,23'R). Thereby, the (13)C NMR shifts of the anomeric position of the beta-glycosides residing at those positions turned out to be excellent probes for the absolute configuration of the attached aglycones. The concise set of data thus obtained also makes clear that the proposed structure of the fattiviracins, a seemingly closely related family of glycoconjugates, is not matched by the published data. Finally, the biological activity of synthetic 1 and some of the key intermediates obtained en route to this natural product was investigated, showing that the entire construct is necessary for appreciable and selective antiviral activity.",10.1021/ja036521e,2003-10-01,0.6035681139833199
Journal of the American Chemical Society,Enantiodivergent Total Syntheses of (+)- and (−)-Scopadulcic Acid A,"The first enantioselective total synthesis of scopadulcic acid A is described. The key step is a cascade intramolecular Heck reaction of a methylenecycloheptene iodide, which generates the B, C, and D rings of the scopadulan ring system in 90% yield as a single stereoisomer. A distinctive feature of these syntheses is the use of stereoselective enolization to dictate which enantiomer of the natural product is produced.",10.1021/ja990404v,1999-05-20,0.6035670774430603
Synlett,Total Synthesis of (±)-Dragmacidin E; Problems Solved and Lessons Learned,"(±)-Dragmacidin E was synthesized in 25 steps from commercially available 7-(benzyloxy)indole. Key transformations in the preparation of this sponge metabolite include (a) a Witkop cyclization to establish the bridging indole core, (b) cyclo-dehydrative pyrazinone formation to unite the two indole-bearing components, and (c) late-stage guanidine installation through chemoselective carbonyl activation. 1 Introduction 2 Results and Discussion 2.1 Model System Synthesis 2.2 (±)-Dragmacidin E Synthesis 3 Conclusions",10.1055/s-0031-1290692,2012-07-16,0.6035632304788753
European Journal of Organic Chemistry,Stereocontrolled Total Synthesis of (+)‐1‐Deoxynojirimycin,"Abstract A highly efficient non‐chiral‐pool synthesis of (+)‐1‐deoxynojirimycin has been realized (24 % overall yield, 11 steps, complete stereocontrol). A novel one‐pot enol ether metathesis/hydroboration/oxidation sequence is used for the selective formation of the all‐ trans cyclic triol. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2009)",10.1002/ejoc.200900595,2009-07-21,0.6035627214936963
Tetrahedron,"Facile synthesis of 6-iodo-2,2′-dipivaloyloxy-1,1′-binaphthyl, a key intermediate of high reactivity for selective palladium-catalyzed monofunctionalization of the 1,1′-binaphthalene core",,10.1016/j.tetlet.2010.05.022,2010-05-17,0.6035616925634449
Tetrahedron,"An original one-pot synthesis of 5-(4-pyridyl)-benzo[c]-2,7-naphthyridine as key intermediate in the synthesis of amphimedine by metalation connected with cross-coupling reaction",,10.1016/s0040-4039(00)78253-0,1994-08-01,0.603560875036413
Tetrahedron,An efficient synthesis of bicyclic β-turn dipeptides via a photochemical key step,,10.1016/s0040-4039(99)01249-6,1999-08-01,0.6035571202114075
Organic Letters,Enantio- and Diastereoselective Total Synthesis of Belzutifan Enabled by Rh-Catalyzed Hydrogenation,"Herein, we report a nine-step synthesis of belzutifan enabled by a novel Rh-catalyzed asymmetric hydrogenation to install the contiguous fluorinated stereocenters with high enantioselectivity. Moreover, the final ketone reduction in the synthesis proceeds with high diastereoselectivity, leading to the expedient assembly of the stereotriad. In contrast to the original 16-step synthesis, this route avoids a lengthy bromination-oxidation sequence and introduces the sulfone functionality via nucleophilic aromatic substitution, obviating the need for transition metal catalysis.",10.1021/acs.orglett.4c00982,2024-05-06,0.6035509397912948
Journal of Organic Chemistry,Enantioselective Total Syntheses of FR901464 and Spliceostatin A and Evaluation of Splicing Activity of Key Derivatives,"FR901464 (1) and spliceostatin A (2) are potent inhibitors of spliceosomes. These compounds have shown remarkable anticancer activity against multiple human cancer cell lines. Herein, we describe efficient, enantioselective syntheses of FR901464, spliceostatin A, six corresponding diastereomers and an evaluation of their splicing activity. Syntheses of spliceostatin A and FR901464 were carried out in the longest linear sequence of 9 and 10 steps, respectively. To construct the highly functionalized tetrahydropyran A-ring, we utilized CBS reduction, Achmatowicz rearrangement, Michael addition, and reductive amination as key steps. The remarkable diastereoselectivity of the Michael addition was specifically demonstrated with different substrates under various reaction conditions. The side chain B was prepared from an optically active alcohol, followed by acetylation and hydrogenation over Lindlar's catalyst. The other densely functionalized tetrahydropyran C-ring was derived from readily available (R)-isopropylidene glyceraldehyde through a route featuring 1,2-addition, cyclic ketalization, and regioselective epoxidation. These fragments were coupled together at a late stage through amidation and cross-metathesis in a convergent manner. Six key diastereomers were then synthesized to probe the importance of specific stereochemical features of FR901464 and spliceostatin A, with respect to their in vitro splicing activity.",10.1021/jo500800k,2014-05-30,0.6035395969295886
Angewandte Chemie International Edition,"Scalable, Enantioselective Synthesis of Germacrenes and Related Sesquiterpenes Inspired by Terpene Cyclase Phase Logic","Terpene cyclase phase: Inspired by this logic, a scalable and enantioselective divergent synthesis of germacrane-type sesquiterpenes is developed. Salient features of this work include: 1) the direct ring closure of a farnesol derivative to the 10-membered carbocycle 1, and 2) subsequent synthetic operations on 1 to gain access to different bicyclic frameworks such as guaianes, cadinanes, selinanes, and elemenes.",10.1002/anie.201206904,2012-10-12,0.6035361070641689
Synlett,A Concise Synthesis of (+)-Polyoxamic Acid and (+)-5-<i>O</i>-Carbamoyl Polyoxamic Acid,"We report the concise synthesis of (+)-polyoxamic acid and (+)-5-O-carbamoyl polyoxamic acid from l-xylose in seven or six steps, respectively. The key steps include a diastereoselective amination of syn-1,2-polybenzyl ethers using chlorosulfonyl isocyanate (CSI) and the one-pot introduction of carbamates into the allylic benzyl ether and primary hydroxyl moieties.",10.1055/s-0028-1083629,2008-11-12,0.6035273859122607
Organic Letters,Synthesis of a Sensitive and Selective Potassium-Sensing Fluoroionophore,"An efficient synthesis is reported that delivers in 5 steps and 52% overall yield a new structurally simplified fluorescent K(+) sensor with improved K(+) sensitivity and selectivity over existing K(+) sensors. The synthesis procedure utilizes a new template-directed oxidative C-N bond-forming macrocyclization reaction and reports new approaches to Pd(0), Sandmeyer-like and metal-free aminoarylations, as well as organotitanium additions to vinylogous sulfonates.",10.1021/ol902836c,2010-02-11,0.6035181187705245
Synlett,Enantioselective Routes to (-)-(<i>R</i>)-Muscone,"The macrocyclic ring of muscone was prepared by Pd-catalyzed cyclization of hexadeca-1,15-diyne, which was converted to cyclopentadec-2-enone. The stereogenic center was introduced by enantioselective Cu-catalyzed conjugate addition of dimethyl­zinc. Because the ee in this step was only moderate, a new route via cyclopentadeca-2,14-dienone was developed. Enantioselective conjugate addition to this substrate led to 14-methylcylodec-2-enone, which was hydrogenated to give (-)-(R)-muscone in high overall yield with up to 98% ee.",10.1055/s-2006-939069,2006-04-24,0.6035103703438274
Journal of the American Chemical Society,Total Synthesis of (−)-Psathyrin A Enabled by Radical Cyclization,"We report herein an enantioselective total synthesis of (-)-psathyrin A, an antibacterial diterpene natural product possessing a unique 6/4/5/5 tetracyclic carbon skeleton and seven contiguous stereocenters, including three adjacent all-carbon quaternary centers. Our synthesis begins with commercially available 2-methyl-2-cyclopenten-1-one, which was subjected to an enantioselective copper/NHC-catalyzed conjugate addition, followed by trapping the resulting enolate with 1-bromo-2-butyne to set up the first two stereocenters, including one all-carbon quaternary center. A Suzuki-Miyaura cross coupling introduces an aromatic ring as the six-membered ring precursor, and a gold(I)-catalyzed Conia-ene reaction constructs the 5/5-fused bicyclic ring system and the second all-carbon quaternary center. Following Birch reduction of the aromatic ring, hydrolysis, and double bond isomerization, a Baran reductive olefin coupling, namely, MHAT-initiated olefin-enone radical cyclization, was employed to construct the four-membered ring and establish the third all-carbon quaternary center. This enabling radical cyclization completed the tetracyclic carbon framework for subsequent peripheral decorations, achieving the first total synthesis of (-)-psathyrin A in 19 steps.",10.1021/jacs.5c11534,2025-08-25,0.6035003120039797
Journal of Organic Chemistry,Intramolecular Cycloadditions of α-Allyloxycarbonylnitrones:  Stereoselective Synthesis of 3-Amino-2(5<i>H</i>)furanones,Treatment of furoisoxazolidines with NaH leads to functionalized 3-amino-2(5H)-furanones through a new rearrangement pattern of the isoxazolidine nucleus. This process has been usefully exploited for the synthesis of enantiomerically pure (5R)-3-alkylamino-5-methyl-2(5H)-furanones.,10.1021/jo025626h,2002-05-10,0.6034952460703331
Journal of Organic Chemistry,Synthesis of Molluscicidal Agent Cyanolide A Macrolactone from <scp>d</scp>-(−)-Pantolactone,"An efficient synthesis of potent molluscicidal agent cyanolide A, a glycosidic 16-membered macrolide, starting from D-(-)-pantolactone is reported. Highly stereoselective aldol, oxa-Michael addition, and Yamaguchi macrolactonization are the key steps in the present synthesis.",10.1021/jo101782q,2010-12-31,0.6034870482025633
Journal of Organic Chemistry,Nonracemic Synthesis of GK–GKRP Disruptor AMG-3969,A nonracemic synthesis of the glucokinase-glucokinase regulatory protein disruptor AMG-3969 (5) is reported. Key features of the synthetic approach are an asymmetric synthesis of the 2-alkynyl piperazine core via a base-promoted isomerization and a revised approach to the synthesis of the aminopyridinesulfonamide with an improved safety profile.,10.1021/jo500336e,2014-03-28,0.6034836287371914
Organic Letters,Asymmetric Total Synthesis of (−)-Panacene and Correction of Its Relative Configuration,"[reaction: see text] The first synthesis of (-)-panacene has been accomplished in concise, highly stereoselective fashion from commercially available 2-methoxy-6-methylbenzoic acid (15 steps, 8.3% overall yield). The synthesis unambiguously establishes the correct relative and absolute configuration of panacene, and demonstrates the serviceability of Pd(II)-mediated tandem intramolecular alkoxycarbonylation-lactonization for the expedient assembly of its tricyclic core, and the dual role of asymmetric alkynylation as an initial source of chirality and as a powerful tool for manipulating diastereoselectivity.",10.1021/ol061385e,2006-07-06,0.6034814786538805
Synthesis,"A Practical and Cost-Effective Method for the Synthesis of Bicyclo[2.2.2]octane-1,4-dicarboxylic Acid","A short and efficient synthesis of bicyclo[2.2.2]octane-1,4-dicarboxylic acid involving the formation of a semicarbazone is developed, and a reproducible protocol for the reduction of this semicarbazone is described. The use of microwaves significantly shortens the duration of the sequence to the diacid compared to the previously described synthetic method. In addition, by shifting from the use of large amounts of Raney nickel to a solid-phase process, both the safety and cost are improved notably.",10.1055/s-0034-1380432,2015-07-02,0.6034797352154905
Journal of the American Chemical Society,Vinyl Quinones as Diels−Alder Dienes: Concise Synthesis of (−)-Halenaquinone,A concise asymmetric synthesis of (-)-halenaquinone is described. The synthesis features a diastereoselective Heck cyclization to set a quaternary center as well as a novel intramolecular inverse-electron-demand Diels-Alder reaction involving a vinyl quinone. The synthesis is highly convergent and features a minimal amount of protecting group manipulations.,10.1021/ja8035042,2008-06-13,0.6034683055858311
Journal of Organic Chemistry,An efficient synthesis of hydroxyethylene dipeptide isosteres: the core unit of potent HIV-1 protease inhibitors,"from commercially available, optically pure D-mannose is described. This synthesis represents a practical and enantioselective entry to a range of other dipeptide isosteres, which are not limited to amino acid derived substituents.",10.1021/jo00023a009,1991-11-01,0.6034566024618546
European Journal of Organic Chemistry,"Concise and Efficient Access to 5,7‐Disubstituted Pyrazolo[1,5‐<i>a</i>]pyrimidines by Pd‐Catalyzed Sequential Arylation, Alkynylation and SN<sub>Ar</sub> Reaction","A simple and efficient method for synthesis of 5,7‐disubstituted pyrazolo[1,5‐ a ]pyrimidines is reported. The synthetic route involved first a one‐pot two‐step synthesis of 7‐substituted pyrazolo[1,5‐ a ]pyrimidin‐5‐ones from the reaction of 3‐aminopyrazole 1 with activated alkynes. These compounds were used as key intermediates to access, with excellent yields, a library of new 5,7‐disubstituted pyrazolo[1,5‐ a ]pyrimidines, which are known for their wide range of biological activities, through C–O bond activation with PyBroP (bromotripyrrolidinophosphonium hexafluorophosphate) as an activator reagent.",10.1002/ejoc.201701024,2017-09-18,0.6034561341588782
Synlett,Cobalt-Mediated Regioselective Synthesis of Substituted Tetrahydroquinolines,"A regioselective synthesis of polycyclic substituted ­pyridines is reported. Key step is the cobalt-catalyzed intramole­cular cyclization of diynenitriles, tethered by a silicon oxygen bond. Subsequent opening of the Si-O ring led then to the related tetra­hydroquinolines.",10.1055/s-2005-871568,2005-01-01,0.6034538059257356
Synthesis,A New and Expedient Total Synthesis of Ochratoxin A and d5-Ochratoxin A,"A new total synthesis of the mycotoxin ochratoxin A (OTA) is presented, in which it is prepared in 9% overall yield from commercially available substrates. The key step consists of the condensation reaction between protected l-phenylalanine and 5-chloro­-8-hydroxy-3-methyl-1-oxoisochromane-7-carboxylic acid (ochratoxin α, OTα). The same strategy could be successfully applied to l-d 5-phenylalanine, leading to the first total synthesis of d 5-OTA, a molecular tracer for the detection and analytical quantification of the natural mycotoxin in food samples by means of stable isotope dilution assay (SIDA).",10.1055/s-0028-1088076,2009-04-27,0.6034451446635727
Tetrahedron,"Diastereoselective Formal Synthesis of the Antifungal Agent, (+)-Preussin. A New Entry to Chiral Pyrrolidines",,10.1016/s0040-4039(97)10468-3,1998-01-01,0.6034392063194818
Angewandte Chemie International Edition,Asymmetric Synthesis of the Nakijiquinones—Selective Inhibitors of the Her-2/Neu Protooncogene,"A Wieland-Miescher type ketone and a tetramethoxyaryl derivative are the key building blocks for the enantioselective total synthesis of nakijiquinone C (1). The nakijiquinones are the only natural products known that selectively inhibit the Her-2/Neu tyrosine kinase, a protooncogene product that is vastly overexpressed in about 30 % of primary breast, ovary, and gastric carcinomas.",10.1002/(sici)1521-3773(19991216)38:24<3710::aid-anie3710>3.3.co;2-8,1999-12-16,0.6034312610313216
Angewandte Chemie International Edition,Asymmetric Synthesis of the Nakijiquinones—Selective Inhibitors of the Her-2/Neu Protooncogene,"A Wieland–Miescher type ketone and a tetramethoxyaryl derivative are the key building blocks for the enantioselective total synthesis of nakijiquinone C (1). The nakijiquinones are the only natural products known that selectively inhibit the Her-2/Neu tyrosine kinase, a protooncogene product that is vastly overexpressed in about 30 % of primary breast, ovary, and gastric carcinomas.",10.1002/(sici)1521-3773(19991216)38:24<3710::aid-anie3710>3.0.co;2-h,1999-12-16,0.6034312610313216
Tetrahedron,"An alternative synthesis of (1R,2S,3R,4R)-2,3-dihydroxy-4-hydroxymethyl-1-cyclopentanamine, a synthetic intermediate of (−)-aristeromycin",,10.1016/s0040-4039(00)96196-3,1987-01-01,0.6034310843008579
Synlett,"Concise Stereocontrolled Synthesis of an α-Carbagalactose Segment of RCAI-56, a Candidate Anticancer Agent","RCAI-56 is a synthetic glycolipid exhibiting a potent antitumor activity by stimulation of natural killer T cells. Tetra-O-benzyl-α-carbagalactose, an important synthetic segment of RCAI-56, was stereoselectively synthesized from 1,4-dichloro-2-butene in nine steps, including the key step of organocatalytic asymmetric Diels–Alder reaction between acrolein and 1-benzyloxybutadiene.",10.1055/s-0037-1611806,2019-04-11,0.6034174914404613
Journal of the American Chemical Society,Asymmetric Copper-Catalyzed Synthesis of α-Amino Boronate Esters from<i>N</i>-<i>tert</i>-Butanesulfinyl Aldimines,"A general and efficient new method for the asymmetric synthesis of alpha-amino boronate esters has been developed. The key step is the Cu(I)-catalyzed addition of bis(pinacolato)diboron to N-tert-butanesulfinyl aldimines, which proceeds in good yields (52-88%) and with very high diastereoselectivities (>96:2) for a variety of aldimine substrates. This method was applied to an efficient synthesis of bortezomib, a potent alpha-amino boronic acid inhibitor of the proteasome that is in clinical use for the treatment of multiple myeloma and mantle cell lymphoma.",10.1021/ja800829y,2008-05-08,0.6034103110128931
Tetrahedron,"1,6-Dihydro-3 (2H)-pyridinones as synthetic intermediates. Formal synthesis of (±)-tabersonine and (±)-catharanthine",,10.1016/s0040-4039(00)78668-0,1980-01-01,0.6034001252834792
European Journal of Organic Chemistry,Enantioselective Synthesis of Caprolactam and Enone Precursors to the Heterocyclic DEFG Ring System of Zoanthenol,"The enantioselective synthesis of both caprolactam and enone synthons for the DEFG ring system of zoanthenol are described. The evolution of this synthetic approach proceeds first through a synthesis using the chiral pool as a starting point. Challenges in protecting group strategy led to the modification of this approach beginning with (±)-glycidol. Ultimately, an efficient approach was developed by employing an asymmetric hetero-Diels-Alder reaction. The caprolactam building block can be converted by an interesting selective Grignard addition to the corresponding enone synthon. Addition of a model alkyne provides support for the late-stage addition of a hindered alkyne into the caprolactam building block.",10.1002/ejoc.201600223,2016-04-01,0.6033975700068956
Tetrahedron,"Hydroformylation of cyclopentenes, novel strategy for total synthesis of carba- d -fructofuranose",,10.1016/s0040-4039(02)00153-3,2002-03-01,0.6033940432184355
Journal of Organic Chemistry,Concise Synthesis of Dihydrochalcones via Palladium-Catalyzed Coupling of Aryl Halides and 1-Aryl-2-propen-1-ols,"An expedient route to substituted dihydrochalcones is reported. The key step is a palladium-assisted arylation of 1-aryl-2-propen-1-ols. This two-step/one-purification process allows the synthesis of a wide range of compounds with original substitution patterns, including polyphenolic derivatives.",10.1021/jo034936c,2004-01-17,0.6033857969221761
Organic Letters,Synthesis of (+)-Lycoricidine by the Application of Oxidative and Regioselective Ring-Opening of Aziridines,"A highly stereoselective total synthesis of (+)-lycoricidine has been described. The salient features of this synthesis are the one-pot elimination followed by allylation reaction, ring-closing metathesis, stereoselective aziridine formation, Dess-Martin periodinane, and silica gel mediated oxidative ring-opening of aziridine to form alpha,beta-unsaturated ketone (allyl amine) and intramolecular Heck cyclization.",10.1021/ol100755v,2010-05-04,0.6033814044213572
Journal of Organic Chemistry,Toward a Synthesis of Hirsutellone B by the Concept of Double Cyclization,"This account describes a strategy for directly forming three of the six rings found in the polyketide natural product hirsutellone B via a novel cyclization cascade. The key step in our approach comprises two transformations: a large-ring-forming, nucleophilic capture of a transient acylketene and an intramolecular Diels-Alder reaction, both of which occur in tandem through thermolyses of appropriately functionalized, polyunsaturated dioxinones. These thermally induced ""double cyclization"" cascades generate three new bonds, four contiguous stereocenters, and a significant fraction of the polycyclic architecture of hirsutellone B. The advanced macrolactam and macrolactone intermediates that were synthesized by this process possess key features of the hirsutellone framework, including the stereochemically dense decahydrofluorene core and the strained para-cyclophane ring. However, attempts to complete the carbon skeleton of hirsutellone B via transannular carbon-carbon bond formation were undermined by competitive O-alkylation reactions. This account also documents how we adapted to this undesired outcome through an evaluation of several distinct strategies for synthesis, as well as our eventual achievement of a formal total synthesis of hirsutellone B.",10.1021/jo401799f,2013-09-13,0.6033702013878399
Tetrahedron,Zincke-bradsher convergent strategy for the synthesis of the ABE tricyclic core of Manzamine A,,10.1016/s0040-4039(97)10744-4,1998-02-01,0.6033684842822514
Journal of Organic Chemistry,Glycosyl Trifluoroacetimidates. 2. Synthesis of Dioscin and Xiebai Saponin I,"Two trisaccharide steroidal saponins, dioscin (1) and Xiebai saponin I (2) with various bioactivities, were efficiently synthesized using the newly developed glycosyl N-phenyl trifluoroacetimidates (10-13) as glycosylation donors. Thus, dioscin was synthesized in five steps and a 33% overall yield from diosgenin and glycosyl trifluoroacetimidates (10 and 11). Xiebai saponin I was synthesized in eight steps and a 32% overall yield from laxogenin and glycosyl trifluoroacetimidates (10, 12, and 13), whereupon, the rare steroid laxogenin was prepared from diosgenin in four steps and an overall 69% yield. All the glycosylation reactions involved in the present syntheses demonstrated that glycosyl trifluoroacetimidates were successful donors comparable to the corresponding glycosyl trichloroacetimidates.",10.1021/jo026103c,2002-11-16,0.6033664476083176
Synlett,An Efficient Synthesis of (±)-Epigallocatechin Gallate by Reductive Intramolecular Etherification,"The synthesis of (±)-epigallocatechin gallate by direct cyclization to the cis-3-acyloxy-2-arylbenzopyranee is described. α-Acyloxylketones, possessing a 2-hydroxylphenyl group at the β-position, underwent intramolecular reductive etherification to give cis-3-acyloxy-2-arylbenzopyran due to neighboring group participation of the acyloxyl group at the α-position. Using this method, we accomplished the stereoselective synthesis of (±)-epigallo­catechin gallate.",10.1055/s-2006-950283,2006-10-01,0.6033644103927791
Tetrahedron,New efficient routes for the preparation of deuterated tetraarylporphyrins,,10.1016/0040-4039(95)00567-v,1995-05-01,0.6033643944724717
Angewandte Chemie International Edition,"Asymmetric Hydrogenation of α,α′‐Disubstituted Cycloketones through Dynamic Kinetic Resolution: An Efficient Construction of Chiral Diols with Three Contiguous Stereocenters","Chiral diols with three contiguous stereocenters were synthesized by a highly enantioselective ruthenium-catalyzed asymmetric hydrogenation of racemic α,α'-disubstituted cycloketones involving dynamic kinetic resolution. This new catalytic asymmetric method provides a concise route to the alkaloid (+)-γ-lycorane.",10.1002/anie.201207561,2012-11-22,0.6033611831117713
Tetrahedron,Total synthesis of (+)-5α-dihydropregnenolone via acetylene-cation cyclization,,10.1016/s0040-4039(00)92748-5,1980-01-01,0.6033598789301122
Organic Letters,Synthesis of the Cancer-Associated KH-1 Antigen by Block Assembly of Its Backbone Structure Followed by One-Step Grafting of Three Fucose Residues,"A robust, convergent, and efficient strategy was developed for the synthesis of the nonasaccharide cancer antigen KH-1. This strategy featured a one-pot block assembly of the linear hexasaccharide backbone using three disaccharides followed by grafting of three fucose residues onto the backbone in one step.",10.1021/acs.orglett.7b03275,2017-11-29,0.6033454631332723
Journal of the American Chemical Society,Enantioselective Total Synthesis of (−)-Caldaphnidine O via a Radical Cyclization Cascade,"The synthetically challenging, diverse chemical skeletons and promising biological profiles of the Daphniphyllum alkaloids have generated intense interest from the synthetic chemistry community. Herein, the first and enantioselective total synthesis of (−)-caldaphnidine O, a complex bukittinggine-type Daphniphyllum alkaloid, is described. The key transformations in this concise approach included an intramolecular aza-Michael addition, a ring expansion reaction sequence, a Sm(II)/Fe(III)-mediated Kagan–Molander coupling, and the rapid formation of the entire hexacyclic ring skeleton of the target molecule via a radical cyclization cascade reaction, which was inspired by an unexpected radical detosylation observed in our recent dapholdhamine B synthesis.",10.1021/jacs.9b07558,2019-08-05,0.6033449190396923
Journal of Organic Chemistry,"Direct Reductive Cyclocondensation of the Nitro Group with the Amido Group: Key Role of the Iminophosphorane Intermediate in the Synthesis of 1,4-Dibenzodiazepine Derivatives","A class of dialkylamino-substituted dibenzodiazepines and their hetero analogues was synthesized by the intramolecular aza-Wittig condensation of the amido group with iminophosphoranes. The one-pot, two-step procedure includes reductive synthesis of the intermediate iminophosphoranes from the corresponding nitroamides and tributylphosphine.",10.1021/acs.joc.8b02682,2019-02-01,0.6033333584241344
Tetrahedron,A carbenoid ring expansion route to the first member of a newly discovered diterpene class. Total synthesis of 18-oxo-3-virgene,,10.1016/s0040-4039(00)60629-9,1993-09-01,0.6033295999253538
Journal of Organic Chemistry,Synthesis of <scp>l</scp>-<i>lyxo</i>-Phytosphingosine and Its 1-Phosphonate Analogue Using a Threitol Acetal Synthon,"The first synthesis of an isosteric phosphonate analogue of the aminotriol lipid phytosphingosine (3), together with an improved synthesis of (2S,3S,4S)-phytosphingosine (2), are described. A key intermediate is 3-pentylidene acetal 9, which was prepared in two steps from dimethyl 2,3-O-benzylidene-d-tartrate (7).",10.1021/jo0493065,2004-07-14,0.6033176150062305
Synthesis,First Total Synthesis of 7-Isovaleryloxy-8-methoxygirinimbine,"We describe the first total synthesis of the pyrano[3,2-a]carbazole alkaloid 7-isovaleryloxy-8-methoxygirinimbine, using a palladium(II)-catalyzed double C–H-bond activation for construction of the carbazole framework and a phenylboronic acid catalyzed annulation of the pyran ring as key steps.",10.1055/s-0037-1609717,2018-04-19,0.6033174237481733
Journal of Organic Chemistry,Total Synthesis of (±)-Przewalskin B,"A concise total synthesis of przewalskin B was accomplished from readily available diene 7. Key features of the synthesis involved a Diels-Alder reaction to install the A ring, a Claisen-Johnson rearrangement to establish the spiro-quaternary center, and a ring-closing metathesis (RCM) of a sterically crowded system to construct the cyclic enone moiety.",10.1021/jo500047q,2014-03-10,0.6033133142753115
Journal of Organic Chemistry,Enantioselective Total Syntheses of Slagenins A−C and Their Antipodes,"Full details of the total syntheses of slagenins A-C (1a-c) and their antipodes (2a-c), novel bromopyrrole alkaloids with a unique tetrahydrofuro[2,3-d]imidazolidin-2-one moiety, are described in which their absolute stereochemistry was established. The key step in the syntheses involves the efficient condensation of dihydrofuran-3-one or glyoxal with urea to construct the slagenin bicycle core.",10.1021/jo026773i,2003-02-19,0.6033124547004599
Tetrahedron,Biogenetic-type three-step synthesis of withasomnine,,10.1016/s0040-4039(00)70758-1,1968-01-01,0.6033076550869417
Angewandte Chemie International Edition,Total Synthesis of (+)‐Linoxepin by Utilizing the Catellani Reaction,"Molecular intelligence: The structurally novel lignan (+)-linoxepin is synthesized in an eight-step sequence. The enantioselective synthesis features the palladium-catalyzed Catellani reaction as the key step. In this highly convergent multicomponent reaction, two new carbon–carbon bonds are formed, one of which results from a CH bond functionalization.",10.1002/anie.201302327,2013-04-16,0.6033043626912554
Tetrahedron,Development of colorimetric receptors for selective discrimination between isomeric dicarboxylate anions,,10.1016/j.tetlet.2006.08.010,2006-08-25,0.6032943250209759
Organic Letters,Synthesis of (−)-Oxycodone,"Our novel synthetic route to (-)-oxycodone, a semisynthetic opioid analgesic, features a palladium-catalyzed direct intramolecular arylation of an aryl bromide, oxidative dearomatization of a dihydrophenanthrenol, formation of a benzylic quaternary carbon by an intramolecular Michael addition of a malonate moiety, and construction of the morphinan skeleton via a Hofmann rearrangement/lactamization cascade.",10.1021/ol503175n,2014-11-25,0.6032928620536733
European Journal of Organic Chemistry,A New Modular and Practical Methodology for the Synthesis of 4‐ or 3‐Substituted Phenyl C‐Nucleosides,"Abstract A novel efficient and practical approach to the synthesis of 4‐ or 3‐substituted phenyl C‐nucleosides has been developed. It consists in coupling of protected halogenose 1 with bromophenylmagnesium bromides followed by acid mediated epimerization to prepare 4‐ or 3‐bromophenyl C‐nucleoside intermediates. Their Pd‐catalyzed cross‐coupling reactions with diverse organometallics followed by deprotection afforded the title nucleoside analogues. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2005)",10.1002/ejoc.200500607,2005-09-08,0.6032922604133689
Journal of Organic Chemistry,Total Syntheses of Epothilones B and D,"Total syntheses of the microtubule stabilizing antitumor drugs epothilone B and D are described, starting from optically pure (S)-malic acid and methyl (R)-3-hydroxy-2-methylpropionate. The synthesis is highly convergent by coupling the three fragments C1-C6 (fragment D), C7-C10 (fragment C), and C11-C21 (fragment B). Key steps are two stereoselective Wittig type olefinations to generate the 12,13- and 16,17-double bonds, an enantioselective Mukaiyama aldol addition to synthesize fragment D, and a sulfone anion allyl iodide alkylation to connect fragments B and C. Finally fragment D was attached to the B + C fragment via aldol addition.",10.1021/jo0007480,2000-10-05,0.6032818533908114
Tetrahedron,Photooxidation of thebaine. A route to 14-hydroxymorphinones and hydrodibenzofuran analogs of methadone,,10.1016/s0040-4039(00)77290-x,1994-08-01,0.6032812210493169
Synlett,Dialkylation of Ethyl 4-(Het)aryl-3-oxobutanoates as a Route to 5-(2-Oxoethyl)cyclopentenones,"An unexplored ability of the long-known chemical transformation, Borsche’s cyclopentenone synthesis (the construction of a 1,4-diketone with subsequent base-induced cyclization), is reported. Double alkylation of ethyl 4-(het)aryl-3-oxobutanoates with 2-bromo-1-(het)arylethanones, with subsequent alkali treatment, provides access to cyclopentenones substituted with a 2-oxoethyl group at the 5-position. These products might serve as valuable synthons for heterocyclization, and this feature was demonstrated by synthesis of 4H-cyclopenta[b]thiophene derivatives.",10.1055/s-0039-1689926,2019-05-24,0.6032667551869919
Organic Letters,Rapid Access to Tetracyclic Core of Wortmannin via an Intramolecular Reductive Olefin Coupling Strategy,"A convergent approach to assemble the fused BCDE tetracyclic framework of wortmannin is presented. This route features a very challenging Suzuki–Miyaura coupling to prepare the fully functionalized furan intermediate, a Negishi-type acylation to unite the two enantio-enriched fragments, and a subsequent hydrogen-atom-transfer-initiated 6- endo radical cyclization to install the central cyclohexadienone moiety, which establishes the C10 all-carbon quaternary stereocenter.",10.1021/acs.orglett.0c02135,2020-08-04,0.6032610734670728
Synthesis,"A Short and Convenient Synthesis of New 1,2-Disubstituted Carbocyclic Nucleoside Analogues of Pyrimidine Based on a Cyclopentene Ring","The synthesis of a new series of 1,2-disubstituted carbonucleoside analogues, pyrimidines of general structure I, is reported. These compounds were prepared in good yield from (±)-6-azabicyclo[3.2.0]hept-3-en-7-one (1) via two synthetic routes that involve NaBH4-mediated C-N bond cleavage as the key step. The uracil derivative Ia was halogenated with Cl, Br, and I at position 5 by treatment with the corresponding N-halosuccinimide.",10.1055/s-2004-815975,2004-01-01,0.60325703425995
Organic Process Research & Development,Some items of interest to process R&D chemists and engineers - Efficient synthesis of HIV protease inhibitor A-792611,,,2006-01-01,0.6032467432014985
Organic Letters,A Divergent Route to Diversity in Macromolecules,"[reaction: see text] A synthetic route for obtaining functional group diversity in macromolecules is described. The route relies on the differential reactivity of substituted dichlorotriazines. Treatment of a triamine core with substituted dichlorotriazines cleanly yields tris(monochlorotriazines). Subsequent S(N)Ar reactions with amine nucleophiles bearing the functional group of interest yield diversity. If the substituent on the dichlorotriazine is a protected nucleophile, deprotection of the functionalized core allows for iterative reactions and the synthesis of star, dendritic, and hybrid macromolecules.",10.1021/ol060559p,2006-04-29,0.6032448204077857
Journal of Organic Chemistry,Diverse Synthesis of Marine Cyclic Depsipeptide Lagunamide A and Its Analogues,"The asymmetric total synthesis of lagunamide A (3.0%, 20 steps longest linear sequence) and its five analogues, including the structure dehydrated at the C37 position, are detailed in this report. The key feature in this diverse synthesis includes the elaboration of four consecutive chiral centers at C37-40 and the final macrocyclization. Starting from chiral aldehyde 10, we synthesized both 1,3-anti and 1,3-syn homoallylic alcohols 20a and 20b through asymmetric aldol condensation and stereoselective allylation. The following esterification to introduce the L-N-Me-Ala unit resulted in significant epimerization. This problem was finally overcome by coupling the alcohols with the corresponding acid chloride of the L-alanine derivative. The key α,β-unsaturated carboxylic acid unit was produced by cross-metathesis (CM) of methacrylaldehyde and related olefins. Interestingly, we found that the C7 configuration dramatically affected the ring closure. Natural lagunamide A (1a), its 39-epimer (1c), and its 2-epimer (1d) were obtained through macrolactamization between alanine and isoleucine moieties.",10.1021/jo401687s,2013-10-03,0.6032446328012778
Journal of Organic Chemistry,A Convergent Synthesis of the Cardenolide Skeleton:  Intramolecular Aldol Condensation via Reduction of α-Bromoketones,"Synthesis of the highly biologically valuable cardenolide backbone was achieved via anionic polycyclization. Bromoketone 18, obtained from double-Michael cycloaddition between cyclohexenone 14 and gamma,delta-unsaturated beta-ketoester 16, was efficiently aldolized under reductive conditions. The highly functionalized tetracyclic compound 52 is an important synthetic intermediate that is potentially amenable to natural cardenolide total synthesis.",10.1021/jo025612b,2002-06-27,0.6032407728905314
Organic Letters,Novel Synthesis of Amphiphilic Dendrons by the Double-Stage Convergent Method,"A series of amphiphilic dendrons (G1-G4) have been designed and synthesized, which have a highly branched aliphatic hydrocarbon skeleton and a hydrophilic hydroxyl functionality to enable conjugation with other substrates. The higher generation dendrons (G3 and G4) were synthesized by a double-stage convergent method, which shortened the synthetic route significantly and provided the products in an efficient manner. The key branching step involved a double alkyl-metal addition to an ester functionality followed by deoxygenation of a resulting tertiary alcohol by triethylsilane.",10.1021/ol901765f,2009-08-31,0.603240364506299
Organic Letters,DDQ-mediated Direct Intramolecular-Dehydrogenative-Coupling (IDC): Expeditious Approach to the Tetracyclic Core of Ergot Alkaloids,An efficient route to 2-oxindoles bearing an all-carbon quaternary center at the pseudobenzylic position has been developed via a DDQ-mediated Intramolecular-Dehydrogenative-Coupling (IDC). The methodology involves a one-pot C-alkylation of β-N-arylamido esters (7) concomitant with dehydrogenative-coupling in the presence of stoichiometric amount of DDQ. A tentative mechanistic route has been proposed for the oxidative coupling. The methodology provides a two-step entry to the ergoline structure of ergot alkaloids.,10.1021/ol400899e,2013-04-29,0.6032326801213111
Organic Letters,A Concise and Stereoselective Synthesis of Hydroxypyrrolidines: Rapid Synthesis of (+)-Preussin,"A convergent and stereoselective synthesis of 2,5-disubstituted 3-hydroxypyrrolidines has been developed that involves reductive annulation of β-iminochlorohydrins, which are readily available from β-ketochlorohydrins, and provides rapid access to a variety of 2,5-syn-pyrrolidines. Application of this process to the concise (three-step) synthesis of the fungal metabolite (+)-preussin and analogues of this substance is reported.",10.1021/ol101631e,2010-08-20,0.6032264054060087
Journal of Organic Chemistry,Total Synthesis of Ripostatin B and Structure–Activity Relationship Studies on Ripostatin Analogs,"Described is the total synthesis of the myxobacterial natural product ripostatin B and of a small number of analogs. Ripostatin B is a polyketide-derived 14-membered macrolide that acts as an inhibitor of bacterial RNA-polymerase, but is mechanistically distinct from rifamycin-derived RNA-polymerase inhibitors that are in use for tuberculosis treatment. The macrolactone ring of ripostatin B features two stereocenters and a synthetically challenging doubly skipped triene motif, with one of the double bonds being in conjugation with the ester carbonyl. Appended to the macrolactone core are an extended hydroxy-bearing phenylalkyl side chain at C13 and a carboxymethyl group at C3. The triene motif was established with high efficiency by ring-closing olefin metathesis, which proceeded in almost 80% yield. The side chain-bearing stereocenter α to the ester oxygen was formed in a Paterson aldol reaction between a methyl ketone and a β-chiral β-hydroxy aldehyde with excellent syn selectivity (dr >10:1). The total synthesis provided a blueprint for the synthesis of analogs with modifications in the C3 and C13 side chains. The C3-modified analogs showed good antibacterial activity against efflux-deficient Escherichia coli but, as ripostatin B, were inactive against Mycobacterium tuberculosis, in spite of significant in vitro inhibition of M. tuberculosis RNA-polymerase.",10.1021/acs.joc.8b00193,2018-03-15,0.6032185051711679
Organic Letters,Total Synthesis of Alotaketal A,"The total synthesis of the cAMP signaling pathway activator (-)-alotaketal A is reported. A convergent approach to the unusual alotane sesterterpenoid skeleton was employed, exploiting a remarkable LiDBB-mediated coupling of an (R)-carvone-derived δ-lactone with an allyl bromide side chain, followed by spiroacetalization.",10.1021/ol302570k,2012-10-24,0.6032175606356989
Journal of Organic Chemistry,Efficient Syntheses of KDR Kinase Inhibitors Using a Pd-Catalyzed Tandem C−N/Suzuki Coupling as the Key Step,A family of four potent KDR kinase inhibitors containing an indol-2-yl quinolin-2-one structure was utilizing a Pd-catalyzed tandem C-N and C-C coupling sequence.,10.1021/jo062228w,2007-01-25,0.6032080944678948
Journal of Organic Chemistry,Synthesis of the Tetrasaccharide Glycone Part of Tetrocarcin A,synthesis of the tetrasaccharide fragment of tetrocarcin A is described. The key feature of this approach is highlighted by the regio- and diastereoselective Pd-catalyzed hydroalkoxylation of ene-alkoxyallenes with an unprotected l-digitoxose glycoside. The subsequent reaction with digitoxal in combination with chemoselective hydrogenation generated the target molecule.,10.1021/acs.joc.2c02832,2023-02-22,0.6032055399227172
Journal of Organic Chemistry,A Convergent Synthesis of 14-Membered F-O-G Ring Analogs of the Teicoplanin Binding Pocket via Intramolecular SNAr Reaction,"An intramol. SNAr reaction for efficient macrocyclization via biaryl ether formation was developed for syntheses of the 14-membered macrocycles I and II (R = NH2, NO2) related to F-O-G ring of teicoplanin. Chloride as well as fluoride could be used as the leaving group in this reaction. However, the latter was preferred since it required milder conditions. Both ortho and para nitro, fluoro disubstituted arom. rings were suitable for the macrocyclization reaction with tethered aryl oxides. The nonproteinogenic alpha -amino acid III, required for the synthesis of II, was prepd. via an asym. Strecker synthesis using (R)-phenylglycinol as a chiral auxiliary. The overall synthetic strategy was convergent, and the cyclization could be performed in the presence of the highly sensitive arylglycine unit without racemization. [on SciFinder (R)]",10.1021/jo00125a026,1995-10-01,0.603202505714091
Journal of the American Chemical Society,Asymmetric Synthesis of the Diterpenoid Marine Toxin (+)-Acetoxycrenulide,"An enantioselective route to the marine toxin (+)-acetoxycrenulide is described. The early stages of the synthesis feature the conversion of ( R )-citronellol into a butenolide whose sole stereogenic center is provided by the terpenic alcohol. Three contiguous chiral carbon atoms are subsequently set in the requisite absolute configuration by conjugate addition of an enantiopure allylphosphonamide reagent. The resulting product is transformed during several steps into a primary selenoxide whose thermal activation in dimethylacetamide at 220 °C promotes sequential 1,2-elimination and Claisen rearrangement. The cyclooctenone core of the target is formed in this step. The final stages of the synthesis involve a series of fully stereoselective reactions including Simmons−Smith cyclopropanation and controlled Dibal-H reduction. The naturally occurring dextrorotatory enantiomer of acetoxycrenulide was ultimately acquired.",10.1021/ja9533609,1996-01-01,0.6032014921626329
Synlett,First Enantioselective Synthesisof a Hydroxyindolizidine Alkaloid from the Ant <i>Myrmicariamelanogaster</i>,"The first enantioselective synthesis of the recently reported ant alkaloid 1 has been achieved starting from commercially available lactam 3 in seven steps and 25% overall yield. The proposed structure of the natural product was confirmed by comparison with synthetic 1 and its absolute configuration established as 3S,5R,8S,9S.",10.1055/s-2008-1078502,2008-06-19,0.6031778739429358
European Journal of Organic Chemistry,Expedient Synthesis of a Linear Nonadecaarabinofuranoside of the <i>Mycobacterium tuberculosis</i> Cellular Envelope,"The synthesis of oligosaccharides is demanding as it requires multiple steps and long reaction sequences. The choice of glycosylation method and protecting groups is very important for the successful synthesis of any oligosaccharide. In this paper, we show that ethynylcyclohexyl carbonate glycosyl donors are excellent for the synthesis of a nonadecasaccharide fragment of the Mycobacterium tuberculosis glycocalyx using a split/react/couple strategy. The synthesis of the target nonadecasaccharide was accomplished using eight different reactions and 23 steps in 6.4 % overall yield.",10.1002/ejoc.201700712,2017-08-29,0.6031747910192903
Tetrahedron,A facile and efficient asymmetric synthesis of (+)-salsolidine,,10.1016/s0040-4039(00)00830-3,2000-07-01,0.603172300606503
Organic Letters,"Total Synthesis of Lamellarins D, H, and R and Ningalin B","A concise total synthesis of lamellarins D (7 steps), H (7 steps), and R (5 steps) and ningalin B (5 steps) is achieved starting from the corresponding aldehydes and amines. The synthesis features three oxidative reactions as key steps in a biomimetic manner, involving an AgOAc-mediated oxidative coupling reaction to construct the pyrrole core, a Pb(OAc)(4)-induced oxidative cyclization to form the lactone, and Kita's oxidation reaction to form the pyrrole-arene C-C bond.",10.1021/ol1027877,2010-12-17,0.6031678652755803
Journal of the American Chemical Society,"Asymmetric Total Synthesis and Biosynthetic Implications of Perovskones, Hydrangenone, and Hydrangenone B","Perovskones and hydrangenones are a family of structurally complex triterpenoids that were mainly isolated from the genus Salvia medicinal plants. These isoprenoids exhibit a broad range of biological activities, such as antitumor and antiplasmodial activities. Here, we report the collective total synthesis of perovskone, perovskones C, D, F, hydrangenone, and hydrangenone B. The key strategies in this work include the following: (1) an asymmetric photoenolization/Diels–Alder reaction was developed to construct a tricyclic ring bearing three contiguous quaternary centers, which was used to build the core icetexane skeleton; (2) a bioinspired Diels–Alder reaction of perovskatone D with trans -α-ocimene was applied to stereospecifically generate perovskones; (3) late-stage oxidations and ring forming steps were developed to synthesize perovskones and hydrangenones. Our synthetic work suggests that (1) perovskatone D may serve as the precursor of the biosynthesis of perovskones and (2) the formation of hydrangenone and hydrangenone B, containing a five-membered D ring, may involve an oxidative ring cleavage and ring regeneration process.",10.1021/jacs.1c02674,2021-04-22,0.6031618888407381
Journal of Organic Chemistry,"One-Pot Synthesis of 7-(Benzimidazol-2-yl)thioxolumazine and -lumazine Derivatives via H<sub>2</sub>SO<sub>4</sub>-Catalyzed Rearrangement of Quinoxalinones When Exposed to 5,6-Diamino-2-mercapto- and 2,5,6-Triaminopyrimidin-4-ols","A facile approach to a range of substituted 7-(benzimidazol-2-yl)thioxolumazines [7-(benzimidazol-2-yl)-2-thioxo-2,3-dihydropteridin-4(1 H )-ones] and 7-(benzimidazol-2-yl)lumazines [7-(benzimidazol-2-yl)pteridine-2,4(1 H,3 H )-diones] is described. These new biheterocyclic systems are obtained via H 2 SO 4 -catalyzed rearrangement of quinoxalin-2-ones in the presence of 5,6-diamino-2-mercapto- and 2,5,6-triaminopyrimidin-4-ols. Thus, benzimidazole and pteridine rings are constructed in one synthetic step. A plausible ANRORC ( a ddition of n ucleophile, r ing o pening and r ing c losure)-type reaction mechanism is proposed. Applying the rearrangement to the aza-analogue of 3-benzoylquinoxalin-2(1 H )-one—i.e., 3-benzoylpyrido[2,3- b ]pyrazin-2(1 H )-one—with 5,6-diamino-2-mercaptopyrimidin-4-ol makes it possible to synthesize inaccessible 7-(1 H -imidazo[4,5- b ]pyridin-2-yl)-6-phenyl-2-thioxo-2,3-dihydropteridin-4(1 H )-one. 7-(Benzimidazol-2-yl)-6-(2-fluorophenyl)-2-thioxo-2,3-dihydropteridin-4(1 H )-ones undergoes intramolecular nucleophilic substitution of fluorine by a nitrogen of the benzimidazole fragment with the formation of benzo[4′,5′]imidazo[1′,2′:1,2]quinolino[4,3- g ]pteridine-2,4(1 H,3 H )-diones as new heterocyclic systems.",10.1021/acs.joc.8b02161,2018-11-15,0.6031582215155208
Synlett,Introduction of the Acetate Unit to the 2-Pyridinone Ring System and Its Application to the Synthesis of (20<i>S</i>)-Camptothecin DE Ring System,The DE ring system of (20S)-camptothecin had been ­prepared from commercially available nicotinic acid in six steps ­utilizing the nucleophilic addition reaction of the silyl ketene acetal to the pyridinone ring as a key step.,10.1055/s-2006-950433,2006-09-01,0.6031556030092755
Synthesis,Photolysis of 4-Phenyl-3-vinylquinolines; A Facile New Route to the Benzo[<i>k</i>]phenanthridine System,,10.1055/s-1978-24918,1978-01-01,0.6031508658047994
Synthesis,"Preparative-Scale, Facile Synthesis of (2<i>R</i>,4<i>E</i>)-2-Methyl-4-hexenal: A Key Intermediate of (2<i>S</i>,3<i>R</i>,4<i>R</i>,6<i>E</i>)-3-Hydroxy-4-methyl-2-methylamino-6-octenoic Acid (MeBmt)","All articles of this category Facile separation and mild acidic hydrolysis of the diastereomeric amides derived from 2-methyl-4-hexenoic acid and L-2-phenylglycinol are used in a rapid, preparative-scale synthesis of (2 R ,4 E )-2-methyl-4-hexenal, a key intermediate of MeBmt.",10.1055/s-1988-27650,1988-01-01,0.6031469355167369
Tetrahedron,Stereoselective synthesis of two highly potent 5-oxo-ETE receptor antagonists,,10.1016/j.tetlet.2015.10.097,2015-11-04,0.6031418491526346
Synlett,"Synthesis of the Novel Tetrahydropyrazolo[3,4-c]pyridin-5-one Scaffold","We report an efficient synthesis of the novel 1,4,6,7-tetra­hydropyrazolo[3,4- c ]pyridin-5-one scaffold with the potential for incorporation of alkyl or aryl substituents at the C-3 and N-6 positions. The route utilises a Dieckmann condensation to install the lactam ring, followed by a hydrazine cyclisation to build the fused pyrazole ring.",10.1055/s-0034-1379504,2014-12-02,0.6031359457883462
Journal of the American Chemical Society,Total Synthesis of (±)-Cephanolides B and C via a Palladium-Catalyzed Cascade Cyclization and Late-Stage sp<sup>3</sup> C–H Bond Oxidation,"Herein, we report the first total syntheses of complex cephalotaxus diterpenoids cephanolide B and C from commercially available 5-bromo-2-methylanisole. Key to the success of this synthetic route is a palladium-catalyzed cascade cyclization reaction, which allowed us to efficiently forge the 6–5–6 cis -fused tricyclic ring systems found in the entire family of cephalotaxus diterpenoids. Additionally, site-selective late-stage sp 3 C–H bond oxidation served as a key strategic element in the chemical synthesis of cephanolide C.",10.1021/jacs.8b03015,2018-04-09,0.6031281788092007
Tetrahedron,Dipolar cyclization reactions in heterocyclic synthesis: a novel route to furanophanes,,10.1016/s0040-4039(00)77672-6,1992-01-01,0.6031240603485961
Journal of Organic Chemistry,"Synthesis of <i>N</i>-{4-[2-(2-Amino-5,6-dihydro-4(3<i>H</i>)-oxo-7<i>H</i>-pyrrolo[2,3-<i>d</i>]pyrimidin-6-yl)- ethyl]benzoyl}-<scp>l</scp>-glutamic Acid:  A Ring-Contracted Analogue of 5,10-Dideaza-5,6,7,8-tetrahydrofolic Acid","This paper describes the synthesis of N -{4-[2-(2-amino-5,6-dihydro-4(3 H )-oxo-7 H -pyrrolo[2,3- d ]pyrimidin-6-yl)ethyl]benzoyl}- l -glutamic acid ( 4 ), which can be viewed as a ring-contracted analogue of 5,10-dideaza-5,6,7,8-tetrahydrofolic acid (DDATHF, 1 ) in which the C-7 methylene group of the latter has been excised and C-6 joined to N-8. This compound exhibits significant activity as an inhibitor of the growth of human (CCRF-CEM) lymphoblastic leukemic cells in vitro and apparently acts by blocking de novo purine biosynthesis through inhibition of glycinamide ribonucleotide formyltransferase (GAR FTase).",10.1021/jo951471k,1996-01-01,0.6031131923295731
Journal of Organic Chemistry,Construction of a CF<sub>3</sub>-Containing Benzofurofuranone Skeleton from Coumarins via Reductive Coupling and Acid-Mediated Ring Contraction,"Magnesium-promoted reductive introduction of a trifluoroacetyl group to coumarin in the presence of ethyl trifluoroacetate and the subsequent treatment with trifluoroacetic acid led to simple access to a trifluoromethylated benzofurofuranone at 8a-position with a high regio- and stereoselectivity. Trifluoromethylated or difluoromethylated benzofurofuranone derivatives were also prepared from coumarins including naturally occurring ones only in two successive steps, which might have potential bioactivity in medicinal chemistry.",10.1021/acs.joc.9b01439,2019-09-05,0.6031053866391693
Tetrahedron,"Asymmetric synthesis of methyl (2 R ,3 S )-3-(4-methoxyphenyl) glycidate, a key intermediate of diltiazem, via Mukaiyama aldol reaction",,10.1016/s0040-4039(00)02235-8,2001-02-01,0.6030939647107657
Journal of Organic Chemistry,Synthesis of Cyclosiphonodictyol A and Its Bis(sulfato),"The first synthesis of the marine benzoxepane hydroquinone cyclosiphonodictyol A and its bis(sulfato) from commercial (+)-sclareolide is reported. The key steps of the synthetic sequence (11 steps, 46% global) are the nucleophilic attack of a hindered tertiary alkoxide, a ring-closing metathesis reaction, and the Diels-Alder cycloaddition of a dienol acetate.",10.1021/acs.joc.9b03434,2020-02-06,0.6030870254246813
Organic Letters,Studies in Marine Polypropionate Synthesis:  Total Synthesis of (−)-Baconipyrone C,"[reaction--see text] An asymmetric total synthesis of the unusual siphonariid metabolite, (-)-baconipyrone C (3), is described. Key steps included a tin(II)-mediated aldol coupling for the preparation of the carboxylic acid 17 and two different boron-mediated aldol additions leading to alcohol 8. Ester formation using modified Yamaguchi conditions gave 24, leading on PMB deprotection to (-)-baconipyrone C.",10.1021/ol000027n,2000-05-03,0.6030848965881276
Tetrahedron,Stereoselective synthesis of (±)-blastmycinome and formal total synthesis of antimycin A3,,10.1016/s0040-4039(00)87970-8,1983-01-01,0.6030848521917189
Tetrahedron,Total synthesis of preswinholide A. 1. Stereoselective synthesis of the C11C23 segment,,10.1016/0040-4039(96)01503-1,1996-09-01,0.6030848521917189
Tetrahedron,"Corrigendum to “An efficient and practical method for the synthesis of mono-N-protected α,ω-diaminoalkanes”",,10.1016/s0040-4039(01)00653-0,2001-06-01,0.6030748954318602
Tetrahedron,"An efficient and practical method for the synthesis of mono-N-protected α,ω-diaminoalkanes",,10.1016/s0040-4039(01)00282-9,2001-04-01,0.6030748954318602
Organic Letters,Total Synthesis of (−)-Dimatairesinol via Regioselective Intermolecular Oxidative Phenol Coupling,"We report the total synthesis of (-)-dimatairesinol, a new dimeric natural lignan possessing a unique interconvertible biaryl skeleton coupled at C-5/C-5 of two units of dibenzyl γ-butyrolactone lignan, namely, matairesinol. The key step involved high regioselective formation of a C-5/C-5 biaryl bond between two units of chiral phenolic γ-butyrolactone (R = H) via a direct and metal-free oxidative phenol coupling mediated by PIFA. On the contrary, C-6/C-6 biaryl coupling exclusively took place when nonphenolic γ-butyrolactones (R ≠ H) were employed, providing the corresponding biaryl products as atropisomers. Synthetic manipulations on the C-5/C-5-biaryl intermediate led to (-)-dimatairesinol.",10.1021/acs.orglett.5c01942,2025-07-10,0.6030673286584199
Tetrahedron,"A convenient, practical synthesis of substituted resorcinols: synthesis of DB-2073 and olivetol",,10.1016/0040-4039(91)80801-c,1991-07-01,0.6030606861283494
Journal of Organic Chemistry,"Synthesis of Indolo[2,3/3,2-<i>c</i>]quinoline through Complementary PIDA/BF<sub>3</sub>·OEt<sub>2</sub> as Well as Pd(0)-Mediated Intramolecular Cyclization of Isomeric <i>N</i>-((Aryl)-<i>N</i>-(phenylsulfonyl)indolyl)methylbenzenesulfonamides","Herein, a straightforward facile synthesis of indolo[2,3- c ]quinoline analogues was reported from 2-arylamino(phenylsulfonyl)methylindoles involving PIDA/BF 3 ·OEt 2 -mediated intramolecular dehydrogenative coupling (IDC) as a key step. Even though isomeric 3-arylamino(phenylsulfonyl)methylindoles, upon interaction with PIDA/BF 3 ·OEt 2, led to complications, synthesis of the indolo[3,2- c ]quinoline framework could be easily achieved from N -(2-iodoaryl)- N -indolylmethylbenzenesulfonamide by employing a Pd(0)-mediated intramolecular cyclization reaction. Under identical conditions, synthesis of indolo[2,3- c ]quinolines was also accomplished from the respective N -(2-iodoaryl)- N -indolylmethylbenzenesulfonamides. The SRB assay of fluorine-bound indoloquinolines displayed nanomolar-level cytotoxicity against a nonsmall lung cancer cell line, NCI-H460.",10.1021/acs.joc.4c01113,2024-08-09,0.6030514181374012
Synlett,"A De Novo Synthetic Route to 1,2,3,4-Tetrahydroisoquinoline Derivatives","A novel synthetic approach was developed for the construction of the 1,2,3,4-tetrahydroisoquinoline framework possessing varied functions. The synthetic strategy was based on oxidative ring opening of some indene derivatives through their C=C bond, followed by double reductive amination of the dicarbonyl intermediates with various primary alkyl- or fluoroalkylamines.",10.1055/s-0037-1609494,2018-03-22,0.6030484123744523
Tetrahedron,"Novel iodine catalyzed diastereoselective synthesis of trans-2,6-disubstituted tetrahydro-2H-pyrans: synthesis of C1–C13 fragment of bistramide-A",,10.1016/j.tetlet.2013.08.085,2013-08-30,0.6030328518666265
Synthesis,New Synthesis of Methyl 7-Oxoheptanoate: An Useful Intermediate for the Preparation of 2-(6-Methoxycarbonylhexyl)-cyclopent-2-en-1-one,,10.1055/s-1983-30584,1983-01-01,0.603029411110289
Tetrahedron,Construction of an advanced taxane synthesis intermediate with an oxygenated B-ring and a non-aromatic C-ring through intramolecular pinacol coupling at C-1C-2,,10.1016/0040-4039(96)00285-7,1996-04-01,0.6030272064378838
Tetrahedron,Chiral synthesis of the hydroxy amino acid moiety of AI-77-B,,10.1016/s0040-4039(01)89006-7,1989-01-01,0.6030182911032257
Journal of the American Chemical Society,Total Synthesis of (−)-Chromodorolide B,The first total synthesis of a chromodorolide diterpenoid is described. The synthesis features a bimolecular radical addition/cyclization/fragmentation cascade that unites butenolide and trans-hydrindane fragments while fashioning two C-C bonds and stereoselectively forming three of the ten contiguous stereocenters of chromodorolide B.,10.1021/jacs.6b00541,2016-02-16,0.6030173675159548
European Journal of Organic Chemistry,"Synthesis of DOHNAA, a <i>Mycobacterium tuberculosis</i> Cholesterol CD Ring Catabolite and FadD3 Substrate","Abstract DOHNAA ( 2 ) is a key catabolite in the Mycobacterium tuberculosis (Mtb) cholesterol degradation pathway. The CoA ester of 2 has been implicated in regulation of gene transcription that is ultimately responsible for degradation of the C and D rings of cholesterol. A synthetic route to 2 is reported here, by a key DMSO‐mediated Morita–Bayliss–Hillman‐type alkylation of the Hajos–Parrish dione. As DOHNAA has to date only been available from microbial sources in very small quantities, the synthesis described will enable further studies of the enzymes involved in cholesterol degradation in Mtb and facilitate ongoing structure–activity studies based on this compound scaffold.",10.1002/ejoc.201500698,2015-08-11,0.6030169816950864
Tetrahedron,Synthesis of (±)-2-methyl-(2′-hydroxy-4′-methylphenyl)-2-hepten-4-one (Turmeronol B),,10.1016/0040-4039(96)00241-9,1996-03-01,0.6030041344793995
Organic Letters,(<i>E</i>)-9-(2-Iodovinyl)-9<i>H</i>-carbazole: A New Coupling Reagent for the Synthesis of π-Conjugated Carbazoles,"The one-pot synthesis of (E)-9-(2-iodovinyl)-9H-carbazole via sequential ruthenium-catalyzed silylative coupling of N-vinylcarbazole with vinyltrimethylsilane and iododesilylation is reported. Its use as a new building block in the palladium-catalyzed Sonogashira and Suzuki-Miyaura coupling reactions to yield new carbazole-containing (E)-but-1-en-3-ynes and (E,E)-buta-1,3-dienes is demonstrated.",10.1021/ol200350a,2011-03-16,0.602994879302598
Tetrahedron,Stereoselective acid-catalyzed homoallylic rearrangement of cyclopropylsilylmethanols: an efficient route to Z-homoallyl derivatives,,10.1016/j.tetlet.2005.07.092,2005-08-10,0.602990913212813
Organic Letters,Enantioselective Total Synthesis of (+)-Sieboldine A,"The first total synthesis of (+)-sieboldine A was completed starting from 5-(p-methoxybenzyloxy)pentyne in 19 steps. The enantioselective Keck allylation provided the dienyne derivative, which was exposed to the Pauson-Khand conditions to afford the bicyclo[4.3.0]nonenone derivative with high stereoselectivity with an ee value of 93%. The following Ueno-Stork reaction formed the cis-hydrindane core with a quaternary carbon center. The late-stage Schmidt glycosylation led to the formation of the N-hydroxyazacyclononane ring.",10.1021/acs.orglett.6b03416,2017-01-02,0.6029776608529805
Organic Process Research & Development,Development of Commercial Manufacturing Processes for Acalabrutinib,"The development of processes to produce the Bruton tyrosine kinase inhibitor, acalabrutinib 1, has resulted in improvements to the yield, cycle time, and operability, to realize a robust commercial manufacturing process. A highly accelerated clinical program meant that numerous key process challenges had to be resolved in a short timeframe. Issues are discussed, such as the uncontrolled epimerization of a chiral center and the control of the acalabrutinib 1 crystallization step, which was prone to oiling. Specifically, work to understand the complex polymorph landscape of a key intermediate (to facilitate resolution of a filtration issue) is described.",10.1021/acs.oprd.2c00304,2022-12-06,0.6029620903492219
Organic Letters,Synthesis of a Reaction Intermediate Analogue of Biotin-Dependent Carboxylases via a Selective Derivatization of Biotin,"[formula: see text] An efficient and practical synthesis of 1, a unique reaction intermediate analogue of biotin-dependent carboxylases, is described. The synthesis features a selective acylation of the 1'-N of biotin. Target 1 inhibits the activity of the biotin carboxylase component of acetyl CoA carboxylase. It is the first known biotin-derived inhibitor of biotin carboxylase and should promote new kinetic and structural studies of the biotin-dependent carboxylases.",10.1021/ol990026z,1999-05-17,0.6029618138382309
Synthesis,"Synthesis of a Sex Pheromone of the Longtailed Mealybug, Pseudococcus longispinus","The synthesis of a recently identified and highly active sex pheromone of the longtailed mealybug, Pseudococcus longispinus is reported. A concise synthetic route, use of the under explored Meyer–Schuster rearrangement, Claisen rearrangement, and ring-closing metathesis are the highlights of this work.",10.1055/s-0033-1338450,2013-05-08,0.602958484322209
Tetrahedron,"A one-pot, efficient and facile synthesis of 4β-arylaminopodophyllotoxins: synthesis of NPF and GL-331 as DNA topoisomerase II inhibitors",,10.1016/j.tetlet.2003.09.110,2003-10-16,0.6029524957838159
Journal of Organic Chemistry,"A Novel One-Step Synthesis of Imidazo[5,1-<i>a</i>]isoquinolines via a Tandem Pd-Catalyzed Alkylation−Direct Arylation Sequence","A palladium-catalyzed/norbornene-mediated one-step synthesis of highly functionalized imidazoles via a sequential alkyl-aryl and aryl-heteroaryl bond formation is devised. This method provides an efficient route to a wide variety of substituted imidazo[5,1-a]isoquinolines from readily accessible N-bromoalkyl imidazoles and aryl iodides.",10.1021/jo802584f,2009-01-02,0.6029451368168658
Tetrahedron,A new approach to the synthesis of thioether phospholipids. Preparation of 1-thiohexadecyl-2-N-acylaminodeoxyglycerophosphocholines,,10.1016/0040-4039(88)80008-x,1988-01-01,0.6029393857523162
Synthesis,Synthesis of Atropisomeric MeOBIPHEP Analogues and Their Application in Silver-Catalyzed Cycloisomerization of Allenols,"The preparation of novel MeOBIPHEP atropisomeric chiral congener ligands via an efficient palladium-catalyzed P–C coupling key step is described. We demonstrate that these palladium-catalyzed conditions are compatible with the brominated MeOBIPHEP backbone. The reaction conditions for asymmetric silver-catalyzed cycloisomerization of γ-allenols were optimized, leading to the first enantioselective catalytic system employing atropisomeric diphosphine ligands as the chiral inducer. The process follows a major 5-exo cyclization via addition of the alcohol moiety to the π-activated allenyl intermediate, leading to vinyltetrahydrofurans with enantiomeric ratios up to 91.5:8.5.",10.1055/s-0035-1562448,2016-07-26,0.6029311116619118
Organic Process Research & Development,Lipase-Catalyzed Regioselective Ester Hydrolysis as a Key Step in an Alternative Synthesis of a Buprenorphine Pro-Drug,This paper describes the development of an alternative route toward a hemiadipic acid pro-drug of buprenorphine. Buprenorphine was acylated with adipic acid monoethyl ester. A regioselective ester hydrolysis using C. antarctica lipase B cleaved the sterically less-hindered alkyl ester in the presence of the more labile phenolic ester. In this manner the pro-drug could be isolated in good yield and high purity.,10.1021/acs.oprd.9b00026,2019-04-18,0.6029295299969026
Organic Letters,Practical and Scalable Synthesis of α-(1→4)-Linked Polysaccharides Composed of 6-<i>O</i>-Methyl-<scp>d</scp>-glucose,"A second-generation synthesis of synthetic 6-O-methyl-D-glucose-containing polysaccharides (sMGPs) is reported. Glycosidation acceptor A and donor B are prepared from alpha-, beta-, and gamma-cyclodextrins in high yields. The glycosidation of A and B, followed by deprotection, furnishes sMGP 12-, 14-, and 16-mers. This synthesis has appealing features such as scalability, operational simplicity, and high overall yield.",10.1021/ol071334x,2007-07-21,0.6029282863968402
Angewandte Chemie International Edition,The Total Synthesis of Eleutherobin: A Surprise Ending,"Stille coupling"" of the vinyl triflate 1 and the stannyl compound 2 is a key step toward the completion of the total synthesis of eleutherobin, a natural product exhibiting taxol-like cytotoxic activity.",10.1002/(sici)1521-3773(19980403)37:6<789::aid-anie789>3.0.co;2-3,1998-04-03,0.6029252009088754
Journal of the American Chemical Society,"Stereoselective Rh<sub>2</sub>(<i>S</i>-IBAZ)<sub>4</sub>-Catalyzed Cyclopropanation of Alkenes, Alkynes, and Allenes: Asymmetric Synthesis of Diacceptor Cyclopropylphosphonates and Alkylidenecyclopropanes","A mild and highly stereoselective rhodium(II)-catalyzed cyclopropanation of alkenes, alkynes, and allenes with diacceptor diazo compounds is reported. Using the phosphonate moiety as an efficient trans-directing group, the first catalytic asymmetric route to diacceptor cycloprop(en)ylphosphonates was developed by employing an α-cyano diazophosphonate and Rh(2)(S-IBAZ)(4) as chiral catalyst. The isosteric character of phosphonic and carboxylic acid derivatives allowed the alternative use of an α-cyano diazo ester in the process, leading to α-cyano cycloprop(en)ylcarboxylates in high yields and stereoselectivities. Taking advantage of the particular reactivity of the cyanocarbene intermediates involved in this system, the scope of compatible substrates could be extended to substituted allenes, leading to the development of the first catalytic enantioselective method for the synthesis of diacceptor alkylidenecyclopropanes.",10.1021/ja3099728,2013-01-04,0.6029187439912105
Angewandte Chemie International Edition,Formal Enantioselective Synthesis of Aplykurodinone‐1,Step economy and simplicity were combined in the asymmetric formal synthesis of aplykurodinone-1 (see scheme; TBS=tert-butyldimethylsilyl). The key features of the strategy involve a one-pot aerobic and directed oxidation/deoxygenation and a late-stage controlled epimerization to form the chiral architecture of the molecule.,10.1002/anie.201301465,2013-05-23,0.6029186645266402
Journal of Organic Chemistry,Epoxide-Initiated Cationic Cyclization of Azides:  A Novel Method for the Stereoselective Construction of 5-Hydroxymethyl Azabicyclic Compounds and Application in the Stereo- and Enantioselective Total Synthesis of (+)- and (−)-Indolizidine 167B and 209D,"A novel and general method has been developed for the stereoselective construction of 5-hydroxymethyl azabicyclic ring skeletons based on epoxide-initiated cationic cyclization of azides. The key cyclization reaction was systematically studied with the model compound, 3-(1-oxa-spiro[2.4]hept-4-yl)propyl azide 3a, and EtAlCl(2) was found to be an ideal choice as the catalyst. The generality of this transformation was further tested with different ring sizes, where six- and seven-membered epoxyazides 3b,c underwent smooth cyclization to give 5-hydroxymethyl azepine 4b and 5-hydroxymethyl azocine 4c, respectively, as a single detectable diastereomer. This novel methodology was elegantly applied in the stereoselective total synthesis of indolizidine alkaloids 167B and 209D. Further, the enantioselective total synthesis of natural and unnatural indolizidine alkaloids 167B and 209D was accomplished by using Sharpless asymmetric dihydroxylation as a key step.",10.1021/jo035258x,2004-04-01,0.6029160363945129
Tetrahedron,"Vicinal alkylation of alkynes. A short route toward Δα,β butenolides, furans and cyclopentenones.",,10.1016/s0040-4039(01)91114-1,1984-01-01,0.602913482522779
Journal of Organic Chemistry,"Vinylogy in Orthoester Hydrolysis: Total Syntheses of Cyclophellitol, Valienamine, Gabosine K, Valienone, Gabosine G, 1-<i>epi</i>-Streptol, Streptol, and Uvamalol A","C7-cyclitols represent an important category of natural products possessing a broad spectrum of biological activities. As each member of these compounds is structurally unique, the usual practice is to synthesize them individually from appropriate polyhydroxylated chiral pools. We have observed an unusual vinylogy in acid mediated hydrolysis of enol ethers of myo-inositol 1,3,5-orthoesters giving a synthetically versatile polyhydroxylated cyclohexenal intermediate. We have exploited this unprecedented reaction for developing a general strategy for the rapid and efficient syntheses of several structurally diverse natural products of C7-cyclitol family. We have made an appropriately protected advanced intermediate 25 in five steps from the cheap and commercially available myo-inositol, and this common intermediate has been used to synthesize eight natural products in racemic form. We could synthesize (±)-cyclophellitol in seven steps, (±)-valienamine in five steps, (±)-gabosine I in five steps, (±)-gabosine G in six steps, (±)-gabosine K in three steps, (±)-streptol in six steps, (±)-1-epi-streptol in two steps, and (±)-uvamalol A in five steps from this intermediate.",10.1021/jo401272j,2013-07-24,0.6029086149195239
Journal of Organic Chemistry,Total Synthesis of Seco (+)- and<i>ent</i>-(−)-Oxaduocarmycin SA:  Construction of the (Chloromethyl)indoline Alkylating Subunit by a Novel Intramolecular Aryl Radical Cyclization onto a Vinyl Chloride,"A practical, total synthesis of seco-(+)-oxaduocarmycin 3a, an analogue of the highly cytotoxic natural product, duocarmycin SA ( 1 ), is described. The 13-step synthesis features a novel and efficient intramolecular aryl radical cyclization onto a vinyl chloride as a direct entry to the (chloromethyl)indoline alkylating subunit 14 . Subsequent resolution, utilizing a preparative Chiralpak AD column, provided enantiomerically pure alkylating subunits 14a and 14b which were elaborated to seco-(+) and ent -(−)-oxaduocarmycins, 3a and 3b, respectively. The natural enantiomer 3a was active at pM concentrations and exhibited 7−50-fold higher potentcy than its enantiomer 3b in in vitro cytotoxicity assays.",10.1021/jo971880b,1997-12-01,0.6029084093396915
Organic Process Research & Development,"Process Development and Scale-up of a Multicomponent Synthesis of a 3-Methyl-1-aryl-1,2,4-triazole Building Block","The classical preparation of 3-methyl-1-aryl-1,2,4-triazoles through an S N Ar reaction pathway results in a mixture of N -regioisomers. Removal of the unwanted isomer reduces the yield and affects processability of the final product. In the presented case study, the target triazole was prepared by an S N Ar route over three steps, in 24% overall yield, with a prohibitive Process Mass Index (PMI) of 300 that made the S N Ar route inadequate for process scale implementation. Bristol-Myers Squibb scientists discovered an improved strategy that allows access to 3-methyl-1-aryl-1,2,4-triazoles directly from anilines and completely obviates formation of N -regioisomers. Further development of this new reaction manifold for process-scale application led to the production of the target triazole in kilogram quantities, as a single regioisomer, with a 3-fold improvement in yield and 7-fold improvement in PMI. Prescale-up thermal analysis indicated that the tosylamide oxime reagent was highly energetic and required proper controls for its scaled-up preparation and handling.",10.1021/acs.oprd.9b00337,2020-01-30,0.6029014743590648
Synlett,Efficient Synthesis of α- and β-2′-Deoxy-heteroaryl-<i>C</i>-nucleosides,A short and efficient method for the synthesis of a series of 2′-deoxy-heteroaryl-C-nucleosides has been developed by the application of aryl-aldol condensation followed by p-toluenesulfonic acid (PTSA)-mediated isopropylidene cleavage and subsequent cycloetherification.,10.1055/s-2008-1072589,2008-04-25,0.6029010190629168
Tetrahedron,Studies toward the total synthesis of garsubellin A: synthesis of 8-deprenyl-garsubellin A,,10.1016/s0040-4039(02)00650-0,2002-05-01,0.6028952819104342
Chemical Science,State-selective frustration as a key driver of allosteric pluripotency,The Rp-cAMPS ligand of protein kinase A switches from agonist to antagonist depending on metabolite and proteomic contexts. We show that the state-selective frustration is a key driver of this allosteric pluripotency phenomenon.,10.1039/d1sc01753e,2021-01-01,0.6028938650773034
Tetrahedron,"Efficient synthesis of phytosiderophores, 3-epi-hydroxymugineic acid and distichonic acid A",,10.1016/s0040-4039(00)74779-4,1992-12-01,0.6028841177840356
Organic Letters,A Homologation Approach to the Synthesis of Difluorinated Cycloalkynes,"Difluorinated cyclooctynes are important reagents for labeling azido-biomolecules through copper-free click chemistry. Here, a safe, scalable synthesis of a difluorinated cyclooctyne is reported, which involves a key homologation/ring-expansion reaction. Sequential ring expansions were also employed to synthesize and study a novel difluorinated cyclononyne.",10.1021/ol500260d,2014-03-03,0.6028804304517237
Synlett,Total Synthesis of (<i>S</i>)-(-)-Curvularin: A Ring-Closing-Metathesis-Based Constructionof the Macrocyclic Framework,"A convergent, flexible, and efficient approach to the synthesis of curvularin is described. Key step is the high-yielding macrocyclic ring formation by ring-closing metathesis (RCM) using the Grubbs second-generation catalyst.",10.1055/s-2008-1078504,2008-06-19,0.6028790967335004
Tetrahedron,"A chiral intermediate for thienamycin analogue synthesis: (,)-4-(2-hydroxyethyl)-3-[()-1-(4-nitrobenzyloxycarbonyloxy)etryl]azetidin-2-one",,10.1016/s0040-4039(01)81324-1,1984-01-01,0.6028751554528431
Journal of Organic Chemistry,"Divergent Total Synthesis of the Lycopodium Alkaloids Huperzine A, Huperzine B, and Huperzine U","Huperzine A, huperzine B, and huperzine U are congeners isolated from the Chinese herb Huperzia serrata (= Lycopodium serratum ) in minuscule amounts. The most efficient total synthesis of huperzine A, the first asymmetric total syntheses of huperzine B, and the first total synthesis of huperzine U have been achieved efficiently in overall yields of 17%, 10%, and 9%, respectively, each spanning 10-13 steps from (R)-pulegone. The featured steps include palladium-catalyzed Buchwald-Hartwig coupling and Heck cyclization reactions and an Ir-catalyzed olefin isomerization reaction. This work has established the absolute configurations of huperzine B and huperzine U and revealed that natural huperzine A, huperzine B, and huperzine U possess the same set of absolute stereochemistries, thus providing support for the potential role of huperzine B and huperzine U in the biosynthesis of huperzine A.",10.1021/jo402419h,2013-12-03,0.6028717695460897
Tetrahedron,On the reaction of chiral sulfinimines with sulfur ylides: a novel route to the asymmetric aziridination,,10.1016/0040-4039(94)02234-3,1995-01-01,0.6028701882733488
Tetrahedron,A short route to the synthesis of pyrroloacridines via Ullmann–Goldberg condensation,,10.1016/j.tetlet.2009.11.044,2009-11-16,0.6028696253751548
Organic Letters,"Asymmetric <i>N</i>-Hydroxyalkylation of Indoles with Ethyl Glyoxalates Catalyzed by a Chiral Phosphoric Acid: Highly Enantioselective Synthesis of Chiral <i>N,O</i>-Aminal Indole Derivatives","A method of SPINOL-derived chiral phosphoric acid catalyzed asymmetric intermolecular N-hydroxyalkylation of multisubstituted indoles with ethyl glyoxalates is described in this report. This protocol provides an alternative, convenient, and direct strategy for efficient access to structurally unique α-chiral indole N,O-acyclic aminals with a broad substrate scope and good to excellent enantioselectivities. The synthetic utility of this methodology is illustrated by a gram-scale experiment and the subsequent efficient synthesis of more complex chiral N,O-aminal indole derivatives.",10.1021/acs.orglett.9b00757,2019-04-10,0.6028676986565442
Organic Process Research & Development,Evaluation and Development of Practical Routes to an Enantiomerically Pure <i>C</i><sub>2</sub>-Symmetric Diamine Building Block,"Several routes to an enantiomerically pure C 2 -symmetric diamine were evaluated and modified to scalable methods. A Zn/Me 3 SiCl-mediated reductive coupling of an imine was found to be superior to the other methods investigated, allowing us to safely prepare the enantiomerically pure diamine also on a large scale. One key step in this method was a highly efficient resolution of a stereoisomeric mixture of the diamine through salt formation with (−)-dibenzoyl- l -tartaric acid. The enantiomerically pure C 2 -symmetric diamine obtained was further used as a key building block for the synthesis of potent Kv1.5 channel blockers.",10.1021/op400292m,2013-11-21,0.6028620263594668
Organic Letters,Toward the Racemic Total Synthesis of Hederacines A and B: Construction of an Advanced Tricyclic Intermediate,"Progress toward the total synthesis of hederacines A and B is described. Our approach involves an allylic cyanate-to-isocyanate rearrangement, eneyne ring-closing metathesis, and a transannular reaction between the C-5 amino group and the C-12 position of the perhydroazuleno[5,6-b]furanone intermediate.",10.1021/ol2004353,2011-04-12,0.6028534359925822
Tetrahedron,A novel route to N-substituted allylamines by the reaction of allylsilanes with (ethoxycarbonyl)nitrene,,10.1016/s0040-4039(00)60626-3,1993-06-01,0.6028521164871438
Tetrahedron,Reaction of -benzoquinone bisacetals with organolithiums. A novel route to substituted veratroles,,10.1016/s0040-4039(00)87299-8,1982-01-01,0.6028521164871438
Journal of the American Chemical Society,First Total Synthesis of (±)-Strychnofoline via a Highly Selective Ring-Expansion Reaction,"An efficient synthesis of the antitumor alkaloid (+/-)-strychnofoline is documented. Key to the development of the highly convergent strategy delineated is the coupling of a cyclic imine with spiro[cyclopropan-1,3'-oxindole], which takes place in a highly diastereoselective manner. The ability to conduct annulation reactions of spirocyclopropyloxindoles with functionalized cyclic imines provides new avenues for the preparation of this important class of biologically active structures.",10.1021/ja027906k,2002-11-22,0.602849772177492
Organic Process Research & Development,An Atom-Efficient Route to Ethyl 3-(difluoromethyl)-1-methyl-1<i>H</i>-pyrazole-4-carboxylate (DFMMP)—A Key Building Block for a Novel Fungicide Family,"A growing number of fluorine-containing active ingredients in the pharmaceutical and agrochemical industries inevitably raises the demand for new fluorinated building blocks. Their availability is mainly constricted by suitable chemistry and available bulk fluorine containing starting materials. Because of the high cost impact especially in the agrochemical industry, the choice of a synthetic route is heavily driven by economic aspects; thus, the environmental profile often is handled as a “secondary factor” or finally falls aside. DFMMP is a key building block for a fast growing new fungicide family, like Syngenta’s Sedaxane, and BASF’s Fluxapyroxad and Bayer’s Bixafen currently made by environmetally less friendly routes. Herein we present a cost-competitive and green route, developed at Solvay laboratories, displaying significantly lower environmental impact.",10.1021/op500128p,2014-06-26,0.6028472185134182
Organic Letters,Total Synthesis of Aigialomycin D:  Surprising Chemoselectivity Dependence on Alkyne Structure in Nickel-Catalyzed Cyclizations,"The total synthesis of aigialomycin D was carried out using a nickel-catalyzed ynal macrocyclization as a key step. This key step allowed macrocycle assembly and formation of a disubstituted alkene and a secondary hydroxyl stereocenter in a single step, although the stereocenter was formed unselectively. An interesting side reaction involving five-membered-ring synthesis by an aldehyde/styrene cyclization was observed when macrocyclization of an alkynyl silane was attempted. A mechanistic basis for this surprising process is provided.",10.1021/ol702961v,2008-02-07,0.6028431748106773
Tetrahedron,"Alternative approaches to (Z)-1,2-bis(2-bromopyridin-3-yl)ethenes, key intermediates in the synthesis of the 1,10-phenanthroline core",,10.1016/j.tetlet.2008.02.112,2008-03-19,0.602836811775874
Synthesis,Advances and Setbacks in the Total Synthesis of the Fungal Metabolite Curvicollide C: Synthesis and Elaboration of Non-Aldol Stereotriads from Gosteli-Type Allyl Vinyl Ethers,"Advances and setbacks are reported in regard to the asymmetric total synthesis of the fungal metabolite curvicollide C relying on a synthetic strategy that exploits non-aldol stereotriads as chiral building blocks. A catalytic asymmetric Gosteli–Claisen rearrangement, a two-step aldehyde-to-alkyne-homologation, and a Julia–Kocienski olefination served as key C/C-connecting transformations.",10.1055/s-0035-1561614,2016-05-10,0.6028356515280676
Synthesis,Synthesis of Dimethyl Phthalide-3-phosphonates and Their Use in the Regiospecific Synthesis of 3-Ylidenephthalides,,10.1055/s-1985-31097,1985-01-01,0.602831438228299
Synthesis,An Efficient Synthesis of 3-Aminocyclopent-2-en-1-one,"All articles of this category A two step, efficient synthesis of the key intermediate 3-aminocyclopent-2-en-1-one starting from 1,3-cyclopentanedione is described. This involves the reaction of ammonia gas with 3-ethoxycyclopent-2-en-1-one.",10.1055/s-1991-26411,1991-01-01,0.6028305131300861
Organic Letters,Toward the Synthesis of Norzoanthamine: Building Carbocyclic Core by a Transannular Michael Reaction Cascade,"A 12-step synthesis of the ABC carbocyclic core of norzoanthamine is described. It features an organocatalytic asymmetric intramolecular aldolization to set the stereochemistry of the entire molecule, a fragment coupling by selective alkylation of a bis-enolate, and a transannular Michael reaction cascade for rapid and stereoselective synthesis of the polycyclic core.",10.1021/ol2024554,2011-09-30,0.602827482914205
Journal of the American Chemical Society,Total Synthesis of (+)-Shearilicine,"Herein we report the first total synthesis of the indole diterpenoid natural product shearilicine by an 11-step sequence via a generalizable precursor to the highly oxidized subclass of indole diterpenoids. A native chiral auxiliary strategy was employed to access the target molecule in an enantiospecific fashion. The formation of the key carbazole substructure was achieved through a mild intramolecular Heck cyclization, wherein a computational study revealed noncovalent substrate-ligand and ligand-ligand interactions that promoted migratory insertion.",10.1021/jacs.2c13584,2023-02-15,0.6028188103065198
Tetrahedron,Isolation and synthesis of a novel β-carboline guanidine derivative tiruchanduramine from the Indian ascidian Synoicum macroglossum,,10.1016/j.tetlet.2005.06.060,2005-07-02,0.6028135603265568
Tetrahedron,A highly convergent and flexible strategy for the synthesis of a-ring aromatic steroids,,10.1016/s0040-4039(01)81993-6,1981-01-01,0.6028114252737514
Tetrahedron,"Stereoselective synthesis of 1,4-dideoxy-1,4-imino-d-allitol and formal synthesis of (2S,3R,4S)-3,4-dihydroxyproline",,10.1016/s0040-4039(03)01366-2,2003-07-01,0.6028024289754618
Tetrahedron,"Synthesis with sulfones (noXXX) : Stereoselective synthesis of arenesulfonyl-1,3-dienes.",,10.1016/s0040-4039(00)88329-x,1983-01-01,0.6028024289754618
Tetrahedron,Cyclopentanoid allylsilanes in synthesis : A stereoselective synthesis of ()-hirsutene,,10.1016/s0040-4039(00)97423-9,1990-01-01,0.6028024289754618
Journal of Organic Chemistry,Diastereoselective Synthesis of CF<sub>3</sub>-Containing Vicinal Diamines,The highly diastereoselective synthesis of CF 3 -containing vicinal diamines by a convenient two-step procedure without the need to isolate the intermediate products is described.,10.1021/acs.joc.7b01261,2017-07-07,0.6027998838205954
Organic Letters,Total Synthesis of (+)-SCH 351448,"A convergent synthesis of (+)-SCH 351448 (1), a monosodium salt of a C(2)-symmetric macrodiolide, is described. Our approach is based on a [4 + 2] annulation with a chiral allyl silane (anti-5c) to assemble the pyran subunits. Homodimerization was carried out in a stepwise fashion; initial esterification at C29' followed by macrocyclization at C29 afforded the desired macrodiolide.",10.1021/ol201863b,2011-08-11,0.6027980764956665
Organic Process Research & Development,"Process Development of the PDE IV Inhibitor 3-(Cyclopentyloxy)-<i>N</i>-(3,5-dichloropyrid-4-yl)-4-methoxybenzamide","Development of an industrial process for 3-(cyclopentyloxy)- N -(3,5-dichloropyrid-4-yl)-4-methoxybenzamide, a potent PDE IV type inhibitor, is described. The rapid identification of scalable reaction conditions allowed pilot-scale synthesis of kilogramme quantities for early clinical evaluation. However, as more compound was demanded, better reaction conditions were required in the interests of safety, economics, and environmental impact. This led to the derivation of a high-yielding and very robust procedure which included various safeguards to ensure that high-quality product was obtained and that new trace impurities were effectively removed. The large-scale oxidation of a benzaldehyde derivative to the corresponding benzoic acid using hydrogen peroxide under aqueous alkaline conditions is described.",10.1021/op9700385,1998-04-11,0.6027938485223214
Tetrahedron,New synthetic method for orsellic acid type macrolides by intramolecular alkylation of protected cyanohydrin. The synthesis of (±)-zearalenone.,,10.1016/s0040-4039(01)90320-x,1981-01-01,0.6027748316724472
Tetrahedron,An efficient route from coumarins to highly functionalized N-phenyl-2-quinolinones via Buchwald–Hartwig amination,,10.1016/s0040-4039(03)00884-0,2003-05-01,0.6027726426458941
Organic Letters,"Synthesis of Enantiopure Bicyclic α,α-Disubstituted Spirolactams via Asymmetric Birch Reductive Alkylation","The synthesis of enantiopure bicyclic alpha,alpha-disubstituted spirolactams is described using a diastereoselective Birch reductive alkylation as the key step. Hydrogenation of the resultant alkylated cyclohexadienes followed by intramolecular cyclization provides access to enantiopure 8-azaspiro[5.6]dodecan-7-ones.",10.1021/ol8029017,2009-01-14,0.6027716105277837
Journal of Organic Chemistry,Syntheses of 2-Aroyl Benzofurans through Cascade Annulation on Arynes,"The highly efficient and expedient route for the syntheses of 2-aroyl benzofurans has been developed via the cascade [2+2] followed by a [4+1] annulation on arynes. The overall transformation proceeded through the formation of ortho-quinone methide by the insertion of transient aryne into N, N-dimethylformamide and subsequent trapping with sulfur ylide. Moreover, this transformation has a broad range of substrate scope with a high functional-group tolerance. This new reaction was successfully utilized in the synthesis of the potent CYP19 aromatase inhibitor and late-stage functionalization on the bioactive complex estrone.",10.1021/acs.joc.8b00360,2018-02-23,0.6027623390059124
Journal of Organic Chemistry,Total Synthesis of (<i>S</i>)-(+)-Imperanene. Effective Use of Regio- and Enantioselective Intramolecular Carbon−Hydrogen Insertion Reactions Catalyzed by Chiral Dirhodium(II) Carboxamidates,"The total synthesis of (S)-(+)-imperanene, a natural product found in Chinese medicine, has been completed in 12 steps from a commercially available cinnamic acid. The key step is highly enantioselective carbon-hydrogen insertion from a diazoacetate using a chiral dirhodium(II) carboxamidate catalyst. An elimination process essential to the construction has been optimized to avoid intramolecular Friedel-Crafts alkylation.",10.1021/jo016220s,2002-04-02,0.6027616100766058
Synlett,Studies toward the Synthesis of Colletotrichamide A: Construction of the C19–C30 Segment of the Molecule,"Abstract A synthesis of the C19–C30 segment of the neuroprotective natural product colletotrichamide A has been achieved by performing a Sonogashira coupling of two advanced intermediate fragments: a vinyl iodide and an alkyne. A Maruoka–Keck allylation, an Evans syn-aldol reaction, and Takai olefinations served as the key steps in the synthesis of the vinyl iodide intermediate, whereas glycosidation and Ohira–Bestmann reactions were used as the pivotal steps for accessing the advanced alkyne intermediate.",10.1055/a-2373-0372,2024-07-25,0.6027596923772709
Organic Process Research & Development,Practical Synthesis of a Heterocyclic Immunosuppressive Vitamin D Analogue,"1α,25-Dihydroxyvitamin D 3 (calcitriol) 1 and synthetic analogues thereof are highly potent compounds with a wide range of pharmacological activity making them of great interest for the pharmaceutical industry. Herein we report an improved synthesis of the calcitriol analogue 2, which features a novel oxazole-containing side chain. The crucial part of the synthesis was the development of a practical route to the β-keto phosphonate 28, allowing an easy introduction of the unnatural side chain by a Wittig Horner reaction.",10.1021/op060130d,2007-01-27,0.6027585764864857
European Journal of Organic Chemistry,Total Synthesis of Resorcylic Acid Lactone (−)‐Neocosmosin A Using Palladium‐Catalyzed α‐Arylation of Enones as the Key Step,"Abstract The total synthesis of the 14‐membered resorcylic acid lactone neocosmosin A is described. The key step in the synthesis is the palladium‐catalyzed α ‐arylation of TES‐enol ethers of enones. The employment of the α ‐arylation approach to this class of resorcylic acid lactones is a new approach, which has the scope of being generalized into a unified approach for the synthesis of this class of natural products.",10.1002/ejoc.202201277,2022-12-05,0.6027562799640699
Journal of the American Chemical Society,Biomimetic Synthesis of (±)-Pinnatal and (±)-Sterekunthal A,Concise biomimetic syntheses of the antimalarial naphthoquinones (+/-)-pinnatal and (+/-)-sterekunthal A are described.,10.1021/ja036026i,2003-07-16,0.6027335372603257
European Journal of Organic Chemistry,"Synthetic Approaches to Novel Thiosugar Scaffolds Containing α,β‐Unsaturated Carbonyl Groups","Abstract The synthesis of new classes of highly functionalized thiosugar derivatives containing α,β‐unsaturated carbonyl functions has been accomplished through simple and efficient strategies. 5‐Thiosugar‐fused butenolides and a 5‐thiohex‐1‐enopyran‐3‐ulose were constructed from easily available starting 3‐uloses by practical and reliable approaches. The reaction sequence used for the bicyclic fused derivatives involved Wittig olefination of protected pento‐ or hexofuran‐3‐uloses, introduction of a sulfhydryl group at C‐5 of the intermediate unsaturated ester and acid‐promoted deprotection, which allowed intramolecular lactonization and conversion into the 5‐thiopyranose form. For the synthesis of a 5‐thiohex‐1‐enopyran‐3‐ulose, a sulfhydryl functionality was introduced at C‐5 on a masked 3‐ulose derived from 1,2:5,6‐di‐ O ‐isopropylidene‐α‐ D ‐ ribo ‐hexofuranos‐3‐ulose. Acidhydrolysis displaced the equilibrium towards the 5‐thiopentopyran‐3‐ulose, which on pyridine‐mediated acetylation underwent 1,2‐elimination of acetic acid to give the desired α,β‐unsaturated 5‐thiopyranulose. This straightforward pathway provided the target compound in 37 % overall yield. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2009)",10.1002/ejoc.200900573,2009-09-01,0.6027283654246615
Organic Process Research & Development,New and Improved Manufacturing Process for Valsartan,"A new and improved industrially viable manufacturing process for valsartan, an antihypertension drug, is described.",10.1021/op9000912,2009-10-13,0.6027230937645117
Journal of the American Chemical Society,Synthetic and Receptor Signaling Explorations of the <i>Mitragyna</i> Alkaloids: Mitragynine as an Atypical Molecular Framework for Opioid Receptor Modulators,"Mu-opioid receptor agonists represent mainstays of pain management. However, the therapeutic use of these agents is associated with serious side effects, including potentially lethal respiratory depression. Accordingly, there is a longstanding interest in the development of new opioid analgesics with improved therapeutic profiles. The alkaloids of the Southeast Asian plant Mitragyna speciosa, represented by the prototypical member mitragynine, are an unusual class of opioid receptor modulators with distinct pharmacological properties. Here we describe the first receptor-level functional characterization of mitragynine and related natural alkaloids at the human mu-, kappa-, and delta-opioid receptors. These results show that mitragynine and the oxidized analogue 7-hydroxymitragynine, are partial agonists of the human mu-opioid receptor and competitive antagonists at the kappa- and delta-opioid receptors. We also show that mitragynine and 7-hydroxymitragynine are G-protein-biased agonists of the mu-opioid receptor, which do not recruit β-arrestin following receptor activation. Therefore, the Mitragyna alkaloid scaffold represents a novel framework for the development of functionally biased opioid modulators, which may exhibit improved therapeutic profiles. Also presented is an enantioselective total synthesis of both (-)-mitragynine and its unnatural enantiomer, (+)-mitragynine, employing a proline-catalyzed Mannich-Michael reaction sequence as the key transformation. Pharmacological evaluation of (+)-mitragynine revealed its much weaker opioid activity. Likewise, the intermediates and chemical transformations developed in the total synthesis allowed the elucidation of previously unexplored structure-activity relationships (SAR) within the Mitragyna scaffold. Molecular docking studies, in combination with the observed chemical SAR, suggest that Mitragyna alkaloids adopt a binding pose at the mu-opioid receptor that is distinct from that of classical opioids.",10.1021/jacs.6b00360,2016-05-18,0.602722415246243
Tetrahedron,A novel reaction of α-chlorosulfides. A new synthesis of diarylethylenes (stilbenes).,,10.1016/s0040-4039(01)87231-2,1973-01-01,0.6027104881779591
Tetrahedron,A novel cyclopentane annulation reaction: New synthesis of estrone,,10.1016/s0040-4039(00)85152-7,1986-01-01,0.6027104881779591
Tetrahedron,Selective ozonolysis of an enyne derivative. The synthesis of cis-jasmone,,10.1016/s0040-4039(01)82498-9,1974-01-01,0.602703804905784
Organic Letters,"Asymmetric Total Synthesis and Na<sub>V</sub>1.8 Inhibitory Evaluation of Villosin B, 17-Hydroxymandarone B, and Their Derivatives","Herein, we present two 17(15→16)- abeo -abietane diterpenoids ( 1 and 2 ) as the first terpenoid-class Na V 1.8 inhibitors, along with their first asymmetric total syntheses to enable in-depth pharmacological studies. Key steps include kinetic resolution of terminal epoxides, bioinspired polyene cyclization, and late-stage photocatalytic benzylic oxidation. Preliminary structural modifications led to 13 derivatives, among which compound 29 exhibited both a 4.3-fold improved potency compared to parent natural product 1 and preserved selectivity across other sodium-gated sodium channels.",10.1021/acs.orglett.5c02746,2025-08-13,0.6026950785987977
Organic Letters,"A Flexible Strategy Based on a <i>C</i><sub>2</sub>-Symmetric Pool of Chiral Substrates: Concise Synthesis of (+)-Valienamine, Key Intermediate of (+)- Pancratistatin, and Conduramines A-1 and E","A new strategy invoking a new application of the [3,3] sigmatropic rearrangement of allylic azides and the presence of a C(2) symmetry element within a pool of chiral substrates was evolved. Not only does this simple flexible strategy provide a concise approach to (+)-valienamine, but it also can readily be adopted for the synthesis of conduramines A-1 and E and the enantiopure azido carbonate 4, a key intermediate of (+)-pancratistatin.",10.1021/ol9016194,2009-08-27,0.6026936516706973
Journal of Organic Chemistry,Total Synthesis of (+)-Aspicilin. The Naked Carbon Skeleton Strategy vs the Bioorganic Approach,"The advantages of the ""naked carbon skeleton"" strategy in the total synthesis of polyoxygenated natural products are demonstrated in the total synthesis of the 18-membered macrolide (+)-aspicilin, 1. This approach employs the easily prepared, nonfunctionalized carbon skeleton of the target molecule, hexadeca-1,3,15-triene, 2. All the required stereogenic carbinol centers are then introduced onto this partially unsaturated hydrocarbon chain using the Sharpless asymmetric dihydroxylation (AD) reaction. Thus, asymmetric synthesis of 1 is achieved in 14 steps and 11% overall yield. Three stereogenic carbinol centers are introduced with very high regio- and enantioselectivity (epimeric excess of 96% at positions 3, 4, and 86% at position 15) by using AD-mix-beta while the fourth is obtained using AD-mix-alpha. This approach is compared with an alternative synthesis of 1 (19 steps and 4.3% overall yield) using chiral building blocks derived from D-arabinose and from the enzymatic reduction of oct-7-yn-2-one, 34, with Thermoanaerobium brockii alcoholdehydrogenase (TBADH).",10.1021/jo9614811,1997-01-01,0.6026874356766011
European Journal of Organic Chemistry,A Three-Step General Synthesis of 2-Azetidinones BearingN-Dehydroamino Acid Side Chains,"An efficient, three-step synthesis of N-vinyl-2-azetidinones 7 starting from α- or β-amino ester imines 3 has been developed. Staudinger reaction between imines 3 and a ketene precursor gave 2-azetidinones 4. Enolate formation on the amino ester moiety of the 2-azetidinone 4, selenation, and finally m-CPBA treatment, afforded N-vinyl-2-azetidinones 7 in fair to excellent yields, with total retention of the stereochemistry of the starting material. Two examples of the use of compounds 7 in preparing bi- and tricyclic 2-azetidinones are presented.",10.1002/(sici)1099-0690(199812)1998:12<2913::aid-ejoc2913>3.0.co;2-4,1998-12-01,0.6026786591189961
European Journal of Organic Chemistry,A Flexible Route to Indole Scaffolds – Formal Synthesis of (±)‐Mersicarpine,"Abstract The formal synthesis of racemic mersicarpine was accomplished in an operationally simple, reliable, and efficient manner in eight isolated steps. The use of a common intermediate increases the degree of synthetic flexibility and allows the construction of two completely different polycyclic alkaloid skeletons.",10.1002/ejoc.201500309,2015-04-23,0.6026718647698561
Tetrahedron,A simple one-pot 2-step N-1-alkylation of indoles with α-iminoketones toward the expeditious 3-step synthesis of N-1-quinoxaline-indoles,,10.1016/j.tetlet.2013.09.113,2013-10-01,0.6026702105128664
Journal of the American Chemical Society,Enantioselective Reduction of 1-Naphthamides by Electrochemical Reduction and Catalytic Asymmetric Hydrogenation in Tandem,"Chiral 1-tetrahydronaphthamides are the core structures of many bioactive molecules, yet their efficient asymmetric synthesis from a simple feedstock remains a challenge. Herein, we present a one-pot synthesis strategy that combines electrochemical reduction and ruthenium-catalyzed asymmetric hydrogenation to achieve the enantioselective reduction of 1-naphthalenamides to chiral 1-tetrahydronaphthamides. The protocol provides a practical platform for selectively constructing high-value chiral tetrahydronaphthenes from readily available naphthalene feedstock, thereby expanding the scope of asymmetric hydrogenation. The synthetic utility of this protocol is further demonstrated through the synthesis of bioactive molecules.",10.1021/jacs.4c18009,2025-03-14,0.6026668448886815
Organic Process Research & Development,Practical Synthesis and Molecular Structure of a Potent Broad-Spectrum Antibacterial Isothiazoloquinolone,"We report the synthesis of the new 2-sulfonylquinolone ethyl 1-cyclopropyl-6,7-difluoro-2-methanesulfonyl-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate ( 5 ). Sulfone 5 is a key intermediate used in the optimized synthesis of the isothiazoloquinolone 9-cyclopropyl-6-fluoro-8-methoxy-7-(2-methylpyridin-4-yl)-9 H -isothiazolo[5,4- b ]quinoline-3,4-dione ( 1 ), a potent broad-spectrum antibacterial agent that is effective against clinically important resistant organisms such as methicillin-resistant Staphylococcus aureus (MRSA). Our synthetic method is free of chromatographic purification and amenable to large-scale synthesis. The molecular structures of 1, 9-cyclopropyl-6,7-difluoro-8-methoxy-9 H -isothiazolo[5,4- b ]quinoline-3,4-dione ( 4 ), 5, and ethyl 2-cyclopropylamino-6,7-difluoro-8-methoxy-4-oxo-4 H -thiochromene-3-carboxylate ( 10 ) were established unambiguously using multinuclear NMR spectroscopy and X-ray crystallography.",10.1021/op700014t,2007-03-16,0.6026654699934133
Tetrahedron,A new route to [3.5.3] armilenium ion,,10.1016/s0040-4039(01)90334-x,1981-01-01,0.6026614888930355
Synthesis,A Flexible Stereocontrolled Synthesis of β-Hydroxy-α-methyl Esters: Application to the Synthesis of Stegobiol and Serricorole,"All articles of this category β -Hydroxy- α -methyl esters have been obtained in a stereocontrolled manner and high enantiomeric and diastereomeric purity from commercially available methyl 3-oxopentanoate and methyl 3-oxobutanoate. The key step is the catalytic hydrogenation of the carbonyl group using ( R )- or ( S )-BINAP-Ru as chiral catalyst followed by asymmetric alkylation. Stegobiol and serricorole, components of the sex pheromone of the drugstore beetle, Stegobium paniceum (L.) and cigarette beetle, Lasioderma serricorne (F.), have been prepared from these chiral building blocks without the need for stoichiometric amounts of chiral auxiliaries. catalytic chiral hydrogenation - ( R )- and ( S )-BINAP-Ru - asymmetric alkylation - stegobiol - serricorole",10.1055/s-1998-2052,1998-04-01,0.6026596127690479
Synlett,"Enantioselective Synthesis of 2,3-Dehydro-3-desoxy-10-oxa Epothilone D",A short and convergent synthesis of a 10-oxa epothilone analog is based on aldolisation of a β-methallyloxy aldehyde derived from methyl 3-hydroxy-2S-methyl propionate followed by ring-closing metathesis,10.1055/s-2003-42034,2003-01-01,0.6026590383591951
Synthesis,Total Syntheses of (+)-Pestaphthalide A and (-)-Pestaphthalide B,"Total syntheses of (+)-pestaphthalide A and (-)-pestaphthalide B were achieved. Key steps are an iridium-mediated meta-selective arylborylation, a Suzuki-coupling/Jacobsen-epoxidation sequence, a stereodivergent epoxide opening and an anionic cyclic carbonate/γ-lactone rearrangement.",10.1055/s-0030-1260166,2011-08-09,0.6026580524042683
Tetrahedron,A new ergostane-type cholesterol biosynthesis inhibitor isolated from Hormoconis resinae,,10.1016/s0040-4039(03)01808-2,2003-09-01,0.6026567674945172
Journal of Organic Chemistry,"Synthesis of Angucyclines. 8. Biomimetic-Type Synthesis of Rabelomycin, Tetrangomycin, and Related Ring B Aromatic Angucyclinones",The angucyclinones with aromatic ring B (1a-c and 2a-c) are prepared in a biomimetic-type synthesis by two successive aldol cyclizations starting from the substituted naphthoquinones 12a-c. In both cyclization steps the C-H acidity of the potential nucleophilic centers determines the mode of cyclization under kinetically controlled conditions. The tetrahydroanthraquinones 13a-c/14a-c are hydroxylated at C-4 to the phenolic anthraquinones 16a-c upon treatment with excess NMO.,10.1021/jo9622587,1997-04-01,0.6026480260409012
Journal of the American Chemical Society,New Class of Nucleophiles for Palladium-Catalyzed Asymmetric Allylic Alkylation. Total Synthesis of Agelastatin A,"New classes of nucleophiles, pyrroles, and N-methoxyamides were developed for Pd-catalyzed AAA reactions. By varying the functional groups at the 2-position of pyrroles, either regioisomer of the piperazinone is available. Using one regioisomer, the total synthesis of (+)-agelastatin A in 10 total steps is accomplished. For this synthesis, a new copper-catalyzed aziridination and an indium-catalyzed oxidative ring opening of a N-tosylaziridine were developed. The feasibility of accessing (-)-agelastatin A from the same enantiomer of the chiral catalyst from the other regioisomeric piperazinone is indicated.",10.1021/ja061105q,2006-04-15,0.6026422922519663
Tetrahedron,Synthetic studies of incednine: synthesis of C1–C13 pentaenoic acid segment,,10.1016/j.tetlet.2009.02.203,2009-03-05,0.6026280278680698
Organic Letters,Silicon Tether-Aided Coupling Metathesis:  Application to the Synthesis of Attenol A,"A new synthesis of attenol A is described. Key features of this work include a crucial silicon tether-aided coupling metathesis step and the use of iodoetherification as an efficient protection method for 1,5-ene-ols. [reaction: see text]",10.1021/ol0268438,2002-10-19,0.6026273016357003
Synlett,"Synthesis of the NaturallyOccurring (-)-1,3,5-Tri-<i>O</i>-CaffeoylquinicAcid","Ribonuclease H (RNase H) is an essential component to the replication of human immunodeficiency virus (HIV), and only a few inhibitors of this enzyme are known. Millenia Hope Pharmaceuticals Inc. found that (-)-1,3,5-tri-O-caffeoylquinic acid is a potent RNase H inhibitor and antiviral agent. A facile route leading to this inhibitor from commercially available (-)-quinic acid is reported within.",10.1055/s-0029-1217183,2009-05-18,0.6026256914139889
European Journal of Organic Chemistry,Synthetic Studies on Dragmacidin D: Synthesis and Assembly of Three Fragments Towards an Advanced Intermediate,"Abstract We report herein the approach to the key advanced intermediate in the synthesis of the bioactive marine natural product dragmacidin D. By employing a modular synthesis strategy of three fragments ( 5 , 7 , and 8 ), the advanced intermediate 3 has been successfully synthesized in 2.5 % yield over 15 steps by starting from nitrotoluene 20 . The synthesis also involves sequential cross‐coupling reactions, namely Sonogashira and Suzuki–Miyaura reactions, so that various analogues can be efficiently synthesized, which will allow the study of structure–activity relationships of dragmacidin D.",10.1002/ejoc.201100242,2011-06-30,0.6026222655490044
Synthesis,Efficient Synthesis of Jolkinolides A and B from Steviol,"Jolkinolides, isolated from Euphorbia fischeriana Steud , are naturally occurring tetracyclic ent -abietane diterpenes, some of which exhibit promising antitumor and other biological activity. An efficient strategy for the synthesis of jolkinolides A and B is described starting from readily available steviol in 10 and 11 steps with total yields of over 10%, respectively.",10.1055/s-0034-1378317,2014-07-09,0.6025997434191319
Journal of Organic Chemistry,Syntheses of Gymnothespirolignans B and C and Non-natural Isomer 9-Epi-gymnothespirolignan B,"Syntheses of polycyclic spiro lignans gymnothespirolignans B and C as well as the unnatural isomer 9-epi-gymnothespirolignan B were accomplished using ( R )-Roche ester and an appropriately substituted fluorenone. Key features of the convergent syntheses include coupling of the fluorenone and an iodo-alkene intermediate derived from ( R )-Roche ester in the presence of the Lewis acid TiCl(O i Pr) 3, C9-O bond formation via an S N 2 reaction with retention of stereochemistry, and diastereoselective hydrogenations of a common alkene intermediate guided by accessibility or positioning by the C8-methoxy.",10.1021/acs.joc.1c01159,2021-07-20,0.6025960204467052
Journal of Organic Chemistry,An Efficient Chemoenzymatic Approach to (<i>S</i>)-γ-Fluoroleucine Ethyl Ester,"[reaction: see text] An asymmetric synthesis of (S)-gamma-fluoroleucine ethyl ester 1 is described. The key transformation involves a lipase-catalyzed dynamic ring-opening of 2-(3-butenyl)azlactone 7b with EtOH to give amide ester (S)-6b in 84% enantiomeric excess. Removal of the N-pentenoyl group with N,N'-dibromodimethylhydantoin in the presence of trifluoroacetic acid afforded the titled compound, which was isolated as its hydrogen sulfate salt in 75% yield and >97% ee.",10.1021/jo047918j,2005-02-11,0.6025939065832064
Synlett,Synthesis of (-)-Hennoxazole A: Integrating Batch and Flow Chemistry Methods,"A new total synthesis of (–)-hennoxazole A is reported. The synthetic approach is based on the preparation of three similarly sized fragments resulting in a fast and convergent assembly of the natural product. The three key reactions of the synthesis include a highly stereoselective 1,5- anti aldol coupling, a gold-catalyzed alkoxycyclization reaction, and a stereocontrolled diene cross-meta­thesis. The synthesis involves integrated batch and flow chemistry methods leading to the natural product in 16 steps longest linear ­sequence and 2.8% overall yield.",10.1055/s-0032-1318109,2013-01-30,0.6025933999591153
Tetrahedron,Synthesis of a novel sphingosine kinase inhibitor (−)-F-12509A and determination of its absolute configuration,,10.1016/j.tetlet.2007.05.043,2007-05-17,0.6025923193579009
Angewandte Chemie International Edition,Concise Total Synthesis of Enigmazole A,"An efficient entry into the phosphorylated marine macrolide enigmazole A is described. Enigmazole A interferes with c-Kit signaling by an as yet unknown mode of action and is therefore a potential lead in the quest for novel anticancer agents. Key to success is a gold-catalyzed cascade comprising a [3,3]-sigmatropic rearrangement of a propargyl acetate along the periphery of a macrocyclic scaffold, followed by a transannular hydroalkoxylation of the resulting transient allenyl acetate. This transformation mandated the use of a chiral gold catalyst to ensure a matching double-asymmetric setting. Other noteworthy steps are the preparation of the oxazole building block by a palladium-catalyzed C-H activation, as well as the smooth ring-closing alkyne metathesis of a diyne substrate bearing a propargylic leaving group, which has only little precedent.",10.1002/anie.201510026,2015-12-10,0.6025914756122074
Organic Letters,Coupling of Alkenes and Alkynes: Synthesis of the C1−C11 and C18−C28 Fragments of Miyakolide,"A transition metal-mediated, atom-economical approach toward the crucial A and D rings of miyakolide is described. A Pd-catalyzed alkyne-alkyne coupling/6- endo- dig cyclization is employed to assemble the A ring fragment. The key D ring pyran is constructed utilizing an Ru-catalyzed alkene-alkyne coupling followed by a Pd-catalyzed allylic alkylation to establish the all-cis stereochemistry.",10.1021/ol800347u,2008-04-22,0.602590526080962
Angewandte Chemie International Edition,Three‐Component Synthesis of Ynediones by a Glyoxylation/Stephens–Castro Coupling Sequence,"One step back, two steps forward! Starting from diverse heterocycles, the title reaction furnishes ynediones under very mild conditions in a direct and preparatively simple one-pot process. The key to avoiding decarbonylation is the CuI-catalyzed Stephens–Castro alkynylation rather than the usually more efficient Sonogashira coupling. In addition, novel highly atom-economical four-component syntheses of various heterocycles can be achieved.",10.1002/anie.201007194,2011-02-23,0.6025859402131883
Synthesis,Synthesis of Model Chromophores Related to the Gold Fluorescent Protein (GdFP),"The two model chromophores 2 and 3 for the core 1 of the gold fluorescent protein (GdFP) were synthesized from commercially available 2-methyl-3-nitroaniline (4) in six synthetic steps and overall yields of 13% and 8%, respectively. The key step of the sequence is the chemoselective, reductive introduction of the amino group after assembly of the Z-configured 5-(indol-3-ylmethylene)imidazolin-4-one skeleton of the chromophore. Compound (Z)-2 was shown to undergo a light-initiated E/Z-isomerization, which allows access also to its E-isomer.",10.1055/s-2007-965945,2007-03-27,0.6025830157152805
Organic Letters,Asymmetric Total Synthesis of Toxicodenane A by Samarium-Iodide-Induced Barbier-Type Cyclization and Its Cell-Protective Effect against Lipotoxicity,"The asymmetric total synthesis of toxicodenane A, a sesquiterpenoid expected to be promising for diabetic nephropathy, was achieved. In the synthesis, a samarium iodide (SmI 2 )-induced Barbier-type cyclization and a regio- and stereoselective allylic oxidation followed by a dehydration cyclization were employed as key steps. Furthermore, the first asymmetric syntheses of both enantiomers were accomplished using the previously mentioned synthetic strategy. Finally, the synthetic compounds significantly inhibited lipotoxicity-mediated inflammatory and fibrotic responses in mouse renal proximal tubular cells.",10.1021/acs.orglett.1c03924,2022-01-03,0.6025767398078534
Journal of Organic Chemistry,Stereoselective Total Synthesis of (±)-Swainsonine Based on Endo Mode Cyclization,"A new stereoselective total synthesis of (+/-)-swainsonine is described. Successive treatment of cis-3,4-epoxy-7-(p-toluenesulfonamido)-1-heptyne with dicobalt octacarbonyl, Lewis acid, and cerium(IV) ammonium nitrate effected stereoselective formation of the trans-2-ethynyl-3-hydroxypiperidine skeleton with retention of configuration at the propynyl center. The piperidine derivative thus prepared was converted into the title compound efficiently.",10.1021/jo980598h,1998-08-08,0.6025680841838686
Journal of Organic Chemistry,Improved Synthesis of Enantiopure 4-Hydroxy[2.2]paracyclophane,4-Hydroxy[2.2]paracyclophane is readily prepared via an improved synthetic protocol from unsubstituted [2.2]paracyclophane. The key step is a Dakin oxidation of 4-formyl[2.2]paracyclophane. This allows a rapid access to large quantities of the product and an easy synthesis of the enantiopure form.,10.1021/jo100468s,2010-06-04,0.6025644913613023
Synlett,An Expeditious Approach to Quinolines via Friedländer Synthesis Catalyzed by FeCl<sub>3</sub>or Mg(ClO<sub>4</sub>)<sub>2</sub>,A mild and efficient route for the synthesis of quinolines and polycyclic quinolines utilizing FeCl3 or Mg(ClO4)2 as a novel catalyst via Friedländer annulation was described.,10.1055/s-2005-917111,2005-01-01,0.6025520019871274
Tetrahedron,"An efficient synthesis of 2-aryl-1,4-diketones via hydroacylation of enones",,10.1016/j.tetlet.2011.12.104,2011-12-31,0.60254956019136
Tetrahedron,Synthesis of some novel D-ring-fused dioxa- and oxazaphosphorinanes in the estrone series,,10.1016/j.tetlet.2005.12.038,2005-12-28,0.6025465634373802
Chemical Science,"Atom and step economical synthesis of acyclic quaternary centers <i>via</i> iridium-catalyzed hydroarylative cross-coupling of 1,1-disubstituted alkenes",predistortion of the reacting intermediate. The key insight disclosed here will underpin the ongoing development of increasingly sophisticated branch selective Murai hydroarylations.,10.1039/d2sc02790a,2022-01-01,0.6025411585877617
Chemical Science,"Unified total synthesis of the natural products endiandric acid A, kingianic acid E, and kingianins A, D, and F","A measure of the strength of a synthetic strategy is its versatility: specifically, whether it allows structurally distinct targets to be prepared. Herein we disclose a unified approach for the total synthesis of natural products of three distinct structural types, all of which occur naturally as racemic mixtures. The point of divergence involves the terminal alkylation of a conjugated tetrayne, and culminates in a significantly shortened synthesis of endiandric acid A (8 steps), the first total synthesis of kingianic acid E (8 steps), and a second-generation synthesis of kingianins A, D, and F (11 steps). Evidence for redox catalysis in the biosynthesis of kingianic acid E is presented.",10.1039/c5sc00794a,2015-01-01,0.602538472628439
European Journal of Organic Chemistry,An Efficient Asymmetric Synthesis of Prostaglandin E1,An asymmetric total synthesis of Prostaglandin E1 (5) has been achieved in a two-component coupling process. The chiral hydroxycyclopentenone 6 was readily available from furan with 96% ee. The key reaction step was a kinetic enzymatic resolution followed by an in situ inversion. A catalytic asymmetric reduction of the γ-iodo vinyl ketone 19 with the Corey CBS catalyst gave the ω-side chain 7 with >96% ee. Conjugate addition using the reaction with dilithiocyanocuprate followed by mild cleavage of the silyl protective groups and enzymatic hydrolysis of the methyl ester 22 gave (–)-PGE15in high yield.,10.1002/(sici)1099-0690(199910)1999:10<2655::aid-ejoc2655>3.0.co;2-2,1999-10-01,0.602537938473079
European Journal of Organic Chemistry,General Approach to Anthrapyran Antibiotics Exemplified by the Synthesis of <i>rac</i>‐γ‐Indomycinone,"Abstract A new general route to the anthrapyran antibiotics is presented, which allows the attachment of various branched side chains. A key step is the Baker–Venkataraman rearrangement of the propionate 9 to the diketone 10 . Acid‐catalyzed cyclization gives the ethyl‐branched anthrapyranone 11 , serving as the starting material for further side‐chain elongation. For example, the ethyl‐substituted anthrapyranones 12a , b , c , the corresponding bromides 13b , c , the phosphonium salts 14b , c , the olefins 22a , c , and the epoxides 23a , c are prepared by starting from 11 . A first example demonstrating the potential of this route is the synthesis of the naturally occurring γ‐indomycinone ( 24b ), prepared bycuprate‐mediated opening of the epoxide 23a .",10.1002/ejoc.201100093,2011-02-18,0.6025266978122742
Tetrahedron,Synthetic studies on halichondrins: A practical synthesis of the C.1C.13 segment,,10.1016/s0040-4039(96)01999-5,1996-11-01,0.6025227540727237
Journal of Organic Chemistry,Tandem Pummerer−Diels−Alder Reaction Sequence. A Novel Cascade Process for the Preparation of 1-Arylnaphthalene Lignans,"The alpha-thiocarbocation generated from the Pummerer reaction of an o-benzoyl-substituted sulfoxide is intercepted by the adjacent keto group to produce an alpha-thio isobenzofuran as a transient intermediate which undergoes a subsequent Diels-Alder cycloaddition with added dienophiles. Acid-catalyzed ring-opening of the cycloadduct followed by aromatization gave an arylnaphthalene derivative. With acetylenic dienophiles, the tandem cyclization-cycloaddition sequence provided tetralones which result from a pinacol-type rearrangement of the primary cycloadducts. The versatility of the approach is highlighted through the synthesis of taiwanin C and E and justicidin E. The alpha-thiocarbocation generated from the Pummerer reaction of benzo[1,3]dioxol-5-yl-[6-[(ethylsulfinyl)methyl]benzo[1,3]dioxol-5-yl)methanone is intercepted by the adjacent keto group to produce an alpha-thioisobenzofuran as a transient intermediate which undergoes a subsequent Diels-Alder cycloaddition with dimethyl maleate. The initially formed Diels-Alder cycloadduct was readily converted to 5-benzo[1,3]dioxol-5-yl-8-(ethylthio)naphtho[2,3-d][1,3]dioxole-6,7-dicarboxylic acid dimethyl ester by loss of water on treatment with p-toluenesulfonic acid. Desulfurization of the thionaphthalene with Ra/Ni followed by hydrolysis of the less hindered methyl ester afforded 5-benzo[1,3]dioxol-5-ylnaphtho[2,3-d][1,3]dioxole-6,7-dicarboxylic acid 6-methyl ester which was further transformed into taiwanin C and justicidin E in good yield. Oxidation of the initial Diels-Alder cycloadduct with NaIO(4) in the presence of RuCl(3) followed by extrusion of ethyl sulfinate gave a naphthol derivative which can be converted into taiwanin E.",10.1021/jo960295s,1996-01-01,0.6025217818839416
Tetrahedron,Facile and improved synthesis of the 2-O-β-d-glucopyranosyl-l-ascorbic acid,,10.1016/j.tetlet.2022.154314,2022-12-20,0.6025204110516132
Journal of Organic Chemistry,Biomimetic Total Synthesis of (+)-Nocardioazine B and Analogs,"Nocardioazines A and B are prenylated, bioactive pyrroloindoline natural products, isolated from Nocardiopsis, with a desymmetrized cyclo - d -Trp- d -Trp DKP core. Based on our deeper biosynthetic understanding, a biomimetic total synthesis of (+)-nocardioazine B is accomplished in merely seven steps and 23.2% overall yield. This pathway accesses regio- and stereoselectively C3-isoprenylated analogs of (+)-nocardioazine B, using the same number of steps and in similar efficiency. The successful strategy mandated that the biomimetic C3-prenylation step be executed early. The use of an unprotected carboxylic acid of Trp led to high diastereoselectivity toward formation of key intermediates exo - 12a, exo - 12b, and exo - 12c (>19:1). Evidence shows that N 1-methylation causes the prenylation reaction to bifurcate away to result in a C2-normal-prenylated isomer. Nocardioazine A, possessing an isoprenoidal-epoxide bridge, inhibits P-glycoprotein (P-gp)-mediated membrane efflux, in multidrug-resistant mammalian colon cancer cells. As several P-gp inhibitors have failed due to their toxicity effects, endogenous amino-acid-derived noncytotoxic inhibitors (from the nocardioazine core) are worthy leads toward a rejuvenated strategy against resistant carcinomas. This total synthesis provides direct access to Trp-derived isoprenylated DKP natural products and their derivatives.",10.1021/acs.joc.2c01120,2022-08-12,0.60251986185757
Journal of Organic Chemistry,Enantiocontrolled Preparation of Indolizidines:  Synthesis of (−)-2-Epilentiginosine and (+)-Lentiginosine,A highly stereoselective approach to (-)-2-epilentiginosine and (+)-lentiginosine has been developed based on a diastereofacially selective cycloaddition of dichloroketene with a chiral dienol ether. The two naturally occurring indolizidines are each obtained enantioselectively (> or = 99:1) in ca. 8.5% overall yield.,10.1021/jo010298r,2001-07-07,0.6025190291099142
European Journal of Organic Chemistry,Total Synthesis and Cytotoxic Activity of 5′‐Hydroxyzearalenone and 5′β‐Hydroxyzearalenone,"An efficient and convergent synthesis of 5′‐hydroxyzearalenone and 5′β‐hydroxyzearalenone, 14‐membered β‐resorcylic acid lactone (RAL) natural products, has been achieved in a longest linear sequence of 19 steps, and a total of 29 steps, starting from commercially available 5‐hexen‐1‐ol and methyl 2‐(3,5‐dimethoxyphenyl)acetate. The key features of our synthesis include a Jacobsen hydrolytic kinetic resolution, a Mitsunobu esterification and (an E )‐selective ring‐closing metathesis (RCM). Our synthesis also highlights the utility of the acetal protecting group for the resorcylate moiety, and its compatibility with RCM reactions for the synthesis of 14‐membered RALs. The cytotoxic activity of both synthetic compounds was evaluated against seven human cancer cell lines. 5′‐Hydroxyzearalenone shows more potent cytotoxic activity against most of the cancer cell lines tested than its epimer, 5′β‐hydroxyzearalenone. Both compounds show significant cytotoxic activity against the C33A cervical cancer cell line, with IC 50 values of 21.33 ± 6.43 µ m and 16.00 ± 12.17 µ m , respectively.",10.1002/ejoc.201701272,2017-10-28,0.6025172949414316
Journal of the American Chemical Society,Stereo-controlled synthesis of dl-prostaglandins F2.alpha. and E2,"A new approach to the synthesis of prostaglandins, designed with the following objectives in mind, is reported. The objectives were: 1) control of stereochemistry; 2) the synthesis of all of the primary prostaglandins and a variety of analogs from a single precursor; and 3) optical resolution at an early stage. The fifteenth synthesis step yielded dl-prostaglandin F2 alpha identical to the natural hormone. Step by step routes of synthesis and stereochemistry are depicted in the text.",10.1021/ja01048a062,1969-09-01,0.6025127157601875
Angewandte Chemie International Edition,Total Synthesis of (−)‐Bastimolide A: A Showcase for Type I Anion Relay Chemistry,"A highly convergent total synthesis of (-)-bastimolide A (1), a polyhydroxy antimalarial macrolide, has been achieved via a longest linear sequence of twenty steps from commercially available glycidyl ethers. Type I Anion Relay Chemistry (ARC) coupling tactics enable rapid construction of the molecule's 1,5-polylol backbone. A late-stage B-alkyl Suzuki-Miyaura union and an Evans-modified Mukaiyama macrolactonization generate the forty-membered Z-α,β-unsaturated macrocyclic lactone.",10.1002/anie.202204884,2022-05-24,0.6025103299864142
Tetrahedron,"First asymmetric synthesis of (2R, 3R)-3-amino-1-benzyl-2-methyl-pyrrolidine via a highly diastereoselective reductive alkylation",,10.1016/s0040-4039(96)02301-5,1997-01-01,0.6025097622905364
Synthesis,"Direct Preparation of (Z,Z)-1,4-Dienic Units with a New C6 Homologating Agent: Synthesis of α-Linolenic Acid","All articles of this category Syntheses of two C6 homologating agents 2a and 2f are described. These agents allow direct access to the ( Z,Z )-1,4-diene unit 3 , a moiety present in a wide number of natural compounds. Compound 2a is prepared in 40% overall yield by selective epoxidation of methoxycyclohexa-1,4-diene followed by oxidative ring cleavage and transacetalization. Compound 2f is obtained in 90% yield by a one-step oxidative dimerization of phosphonium salt 1 . A short synthetic application of these two new C6 homologating agents to the synthesis of α -linolenic acid is described. C6 homologation - ( Z,Z )-1,4-diene unit - acetal - Wittig - all ( Z )-polyunsaturated fatty acids",10.1055/s-1995-3906,1995-03-01,0.602497456277934
Synlett,Stereocontrolled Total Synthesis of Antimalarial (+)-Axisonitrile-3,"Here we describe the total synthesis of the antimalarial sesquiterpene, (+)-axisonitrile-3. Three key features of this synthesis are: (i) non-Evans syn-aldol reaction of an isovaleric acid derivative bearing a chiral oxazolidinethione and crotonaldehyde with high diastereoselectivity, (ii) Claisen rearrangement of alkenyl dihydropyran affording spiro[4.5]decane with requisite functionalities, and (iii) highly stereoselective reduction in the sterically congested O-methyl oxime system.",10.1055/s-0029-1217826,2009-08-17,0.6024962871437853
Angewandte Chemie International Edition,Synthesis of Cyclic Alkenyl Triflates by a Cationic Cyclization Reaction and its Application in Biomimetic Polycyclizations and Synthesis of Terpenes,"Cyclic alkenyl triflates are useful intermediates in organic synthesis usually synthesized from ketones through a reaction involving enolization and trapping with a triflating agent. This sequence suffers from some stereochemical drawbacks owing to the basic conditions required. Herein, we describe a new acid-mediated cationic cyclization reaction of enyne derivatives (or alkynols) to access cyclic alkenyl triflates. This new atom-economical process is high yielding, scalable, technically very simple, proceeds without the need of any metallic reagent or catalyst, and more importantly, it complements and challenges conventional methodologies. We have also developed new biomimetic cationic cyclization reactions to yield interesting polycyclic compounds. As a demonstration of the potential of this method in the context of total synthesis, we have synthesized two terpenes: austrodoral and pallescensin A. Using the cationic cyclization in the key step of the synthetic routes allowed the synthesis of these natural products in a very simple, concise, scalable, and efficient way.",10.1002/anie.201508077,2015-11-04,0.6024957812229343
Journal of Organic Chemistry,"Stereocontrolled Synthesis of Substituted Chiral Piperidines viaOne-Pot Asymmetric 6π-Azaelectrocyclization: Asymmetric Syntheses of(−)-Dendroprimine, (+)-7-Epidendroprimine, (+)-5-Epidendroprimine, and (+)-5,7-Epidendroprimine","The asymmetric one-pot 6π-azaelectrocyclization of alkenyl vinyl stannane, ethyl (Z)-2-iodo-4-oxobutenoate, and (-)-7-isopropyl-cis-aminoindanol in the presence of a Pd(0) catalyst stereoselectively produced the tetracyclic aminoacetal compounds, resulting from the four-bond formation accompanying by controlling the stereochemistry at the two asymmetric centers. The produced cyclic aminoacetals can be regarded as synthetic precursors of substituted chiral piperidines, and the syntheses of 2,4- and 2,4,6-substituted piperidines were realized from the obtained aminoacetals by the stereoselective hydrogenation of the double bond conjugated with the C-4 ester group and alkylation at the aminoacetal moiety. In addition, the stereoselective synthesis of an indolizidine alkaloid, (-)-dendroprimine, and its three stereoisomers, (+)-7-epidendroprimine, (+)-5-epidendroprimine, and (+)-5,7-epidendroprimine, were achieved.",10.1021/jo202350z,2012-01-19,0.6024921305543801
Organic Process Research & Development,Facile Production Scale Synthesis of (<i>S</i>)-Taniguchi Lactone: A Precious Building-Block,"A cost-efficient and facile synthesis of ( S )-4-vinyldihydrofuran-2( 3H )-one ( ( S ) -1 ), better known as ( S )-Taniguchi lactone, is described. Racemic Taniguchi lactone rac -1 was ring-opened with ( S )-1-benzylmethylamine providing a diastereomeric mixture of hydroxyl-amides. The desired diastereomer ( S,S ) -2 was isolated by crystallization and subjected to acidic hydrolysis to release enantiopure title compound in good overall yield with an er in excess of 99%. The process was successfully scaled up to kilogram quantities.",10.1021/op500096j,2014-04-22,0.6024902552439553
Journal of Organic Chemistry,A Practical Synthesis of Cabergoline,"Cabergoline is an N-acylurea derived from 9,10-dihydrolysergic acid, which is a potent prolactin inhibitor. It is marketed by Pharmacia as Dostinex for the treatment of hyperprolactinemia and is currently under active development for the treatment of a variety of CNS disorders. In the existing process, the N-acylurea is formed by the reaction of an amide with a large excess of ethyl isocyanate at elevated temperatures. An improved process was developed that eliminates this hazardous reaction. The amide is reacted with phenyl chloroformate and then with ethylamine, which provides a mild and efficient means of forming the unsymmetrical N-acylurea.",10.1021/jo0203847,2002-09-12,0.602488759798611
Synlett,Cycloaddition of an Enantiopure Cyclic Nitrone to Maleate: Straightforward Synthesis of the Necine Base (-)-Hastanecine,"All articles of this category A formal synthesis of the necine base (-)-hastanecine, subunit of the pyrrolizidine alkaloids hastacine and punctanecine, is reported. The key intermediate 7 is synthesized in five steps from dimesylate 11 , derived from L-malic acid, in 28.3% overall yield. The correct absolute stereochemistry at C7 in the target compound is attained by means of a Mitsunobu reaction on dimesylate 11 . The desired stereochemistry at the remaining stereogenic centres (C1 and C7a) derives from a highly preferential exo-anti approach in the key cycloaddition of nitrone 9 (obtained with complete regiocontrol) to dimethyl maleate. pyrrolizidine alkaloids - (-)-hastanecine - necine bases - Mitsunobu reaction - enantiomerically pure cyclic nitrones",10.1055/s-1997-3222,1997-05-01,0.6024886777606122
Organic Process Research & Development,"Efficient Enzymatic Process for the Production of (2 <i>S</i> )-4,4-Difluoro-3,3-dimethyl- <i>N</i> -Boc-proline, a Key Intermediate in the Synthesis of HIV Protease Inhibitors","(2 S )-4,4-Difluoro-3,3-dimethyl- N -Boc-proline ( 3 ) is a key intermediate for the synthesis of HIV protease inhibitors. Here, several approaches for the preparation of enantiopure 3 and its analogues are disclosed. Among these methods, one strategy relies on resolving the racemic methyl ester of 3 through a protease-catalyzed enantioselective hydrolysis. Despite the fact that this resolution was applied to prepare kilogram quantities of optically pure acid 3 for clinical trials, this process suffered from low efficiency, high cost and difficulties in improvement by medium engineering. An alternative much more efficient and cost-effective enzymatic process was therefore developed by switching the protective group of the proline esters from a Boc to a benzyl moiety. This new process has a much higher throughput (6.3 mmol/h/L vs 0.11 mmol/h/L), and the cost of the process was also dramatically reduced to only 5% of the protease resolution process.",10.1021/op060004+,2006-03-17,0.6024876595253131
Synlett,Model Studies Towards the Total Synthesis of the Anticancer Agent Roseophilin,"In our new approach to the anticancer agent roseophilin (1), a concise, stereocontrolled synthesis of the bicyclic model system 16 was achieved. Key steps include a diastereoselective Ireland-Claisen rearrangement and a stereoselective construction of the hexahydro-cyclopenta[b]pyrrol-6-one core via a tandem intramolecular aza-Wittig/[3+2]-cycloaddition sequence.",10.1055/s-2003-41498,2003-01-01,0.6024833992266285
Journal of the American Chemical Society,Total Synthesis of Aeruginosin 98B,The first total synthesis of aeruginosin 98B was accomplished. The key step is a highly diastereoselective Pd-catalyzed intramolecular asymmetric allylic alkylation reaction of a diastereomeric mixture of allylic carbonates that is enabled by the use of racemic phosphine ligand L1.,10.1021/ja309947n,2012-11-01,0.6024821136636341
European Journal of Organic Chemistry,Novel Dithienylethenes with Extended π‐Systems: Synthesis by Aldol Condensation and Photochromic Properties,"Abstract A facile and stereoselective route to symmetric π‐extended dithienylethene derivatives is described. The key step of this route is an aldol condensation of 1,2‐bis(5‐formyl‐2‐methylthiophen‐3‐yl)cyclopentene with a large variety of acyl compounds. All synthesized photoswitches can be reversibly converted into the closed form by irradiation with visible light. The photochromic properties of nine new dithienylethenes are discussed.",10.1002/ejoc.201000721,2010-08-25,0.602471897822791
Organic Letters,"Concise Synthesis of Pochonin A, an HSP90 Inhibitor",[chemical reaction: see text]. An expedient synthesis of (-)-pochonin A is reported (seven steps). This natural product is closely related to radicicol and was shown to be a 90 nM inhibitor of HSP90.,10.1021/ol052263+,2005-11-16,0.602465107918545
Journal of Organic Chemistry,Stereoselective Total Synthesis of Nemorosone,"The highly stereoselective total synthesis of nemorosone via a new approach to the bicyclo[3.3.1]nonane-2,4,9-trione core which features intramolecular cyclopropanation of an α-diazo ketone, stereoselective alkylation at the C8 position, and regioselective ring-opening of cyclopropane is described. The total synthesis of nemorosone includes chemo- and stereoselective hydrogenation directed by the internal alkene.",10.1021/jo300646j,2012-05-07,0.6024609686166374
Organic Letters,"Development of a Late-Stage Diversification Strategy for the 4- and 5-Positions of 4,5,6-Trisubstituted Indazoles","Indazoles represent a privileged motif in drug discovery. However, the formation of highly substituted indazoles can require the execution of lengthy synthetic routes with minimal opportunities to introduce diversity. In this report, we disclose the development of a late-stage diversification strategy for the 4- and 5-positions of 4,5,6-trisubstituted indazoles. A regioselective C-H functionalization and subsequent nucleophilic aromatic substitution provide two sequential points of diversification. The synthetic sequence delivers rapid access to an array of 4,5,6-trisubstituted indazoles in only four steps from readily available starting materials.",10.1021/acs.orglett.0c03440,2020-11-09,0.6024595330626239
Tetrahedron,A practical chemoenzymatic synthesis of a key intermediate of antifungal agents,,10.1016/s0040-4039(01)00425-7,2001-05-01,0.6024589265156848
Journal of Organic Chemistry,One-Pot Synthesis of 3-Hydroxyquinolin-2(1<i>H</i>)-ones from <i>N-</i>Phenylacetoacetamide via PhI(OCOCF<sub>3</sub>)<sub>2</sub>-Mediated α-Hydroxylation and H<sub>2</sub>SO<sub>4</sub>-Promoted Intramolecular Cyclization,"A clean, one-pot synthesis of the biologically important 3-hydroxyquinolin-2(1H)-one compounds has been realized from the readily available N-phenylacetoacetamide derivatives through a PhI(OCOCF3)2-mediated α-hydroxylation and a H2SO4-promoted intramolecular condensation. The hydroxyl group in the generated α-hydroxylated intermediate can be well tolerated in the second H2SO4-promoted cyclization step.",10.1021/jo400541s,2013-05-08,0.6024534104877788
Tetrahedron,A novel cyclization/oxidation strategy for a two-step synthesis of (Z)-aurone,,10.1016/j.tetlet.2017.02.074,2017-02-27,0.6024517549347156
Tetrahedron,A highly enantioselective synthesis of (−)- and (+)-juglomycin A through Dötz annulation and asymmetric dihydroxylation,,10.1016/j.tetlet.2008.04.059,2008-04-13,0.602447360798643
Journal of Organic Chemistry,Diastereoselective Pictet–Spengler Based Synthesis of a Chiral Tetrahydroisoquinoline D1 Potentiator,A practical synthesis of a D1 potentiator chiral tetrahydroisoquinoline has been accomplished employing diastereoselective Pictet–Spengler methodology to access the required trans-stereochemistry. A dynamic kinetic resolution by crystallization gives high yields of a N -(phenylsulfonyl)alkyloxazolidinone that is converted to an acyl iminium ion when exposed to a variety of Lewis acids resulting in a highly diastereoselective Pictet–Spengler cyclization. An eight-step linear synthesis that starts with commercially available R -2-bromophenylalanine affords the chiral tetrahydroisoquinoline 1 in 54% overall yield.,10.1021/acs.joc.0c00177,2020-05-13,0.6024469255107251
Journal of the American Chemical Society,Total Synthesis of <i>Campylobacter jejuni</i> NCTC11168 Capsular Polysaccharide via the Intramolecular Anomeric Protection Strategy,"The infection of Campylobacter jejuni results in a significant diarrhea disease, which is highly fatal to young children in unindustrialized countries. Developing a new therapy is required due to increasing antibiotic resistance. Herein, we described a total synthesis of a C. jejuni NCTC11168 capsular polysaccharide repeating unit containing a linker moiety via an intramolecular anomeric protection (iMAP) strategy. This one-step 1,6-protecting method structured the challenging furanosyl galactosamine configuration, facilitated further concise regioselective protection, and smoothed the heptose synthesis. The tetrasaccharide was constructed in a [2 + 1 + 1] manner. The synthesis of this complicated CPS tetrasaccharide was completed in merely 28 steps, including the preparation of all the building blocks, construction of the tetrasaccharide skeleton, and functional group transformations.",10.1021/jacs.3c00102,2023-04-11,0.6024347320272294
Tetrahedron,Enantioselective allylation of α-ketoester oximes with an external chiral ligand: Asymmetric synthesis of allylglycines and allylalanine,,10.1016/s0040-4039(96)02112-0,1996-12-01,0.6024343668772354
Synthesis,A Concise and Flexible Synthesis of C2′-Sulfonylated Quinine Derivatives,"Abstract A concise and flexible procedure for the synthesis of structurally novel C2′-sulfonylated quinine derivatives is developed. Through careful optimization of the reaction conditions, most of the reactions can be performed in high yields at gram or several hundreds of milligram scale. Since cinchona-based derivatives are widely used in asymmetric catalysis, the synthetic route developed herein provides an efficient and practical pathway for the diverse synthesis of new cinchona derivatives as potential chiral ligands or multifunctional organocatalysts.",10.1055/a-2135-9037,2023-07-24,0.6024213936413103
Journal of the American Chemical Society,A Concise Total Synthesis of (+)-Scholarisine A Empowered by a Unique C–H Arylation,"The structurally unique akuammiline alkaloid (+)-scholarisine A was synthesized in 14 steps from a known enone (15 steps from commercial materials) through a route empowered by a unique C-H arylation reaction to forge its polycyclic core. Additional key steps include a pyrone Diels-Alder reaction and a radical cyclization/Keck allylation to fashion the core cage polycycle and one of the molecule's quaternary centers, as well as the use of a carefully positioned pendant hydroxyl group to facilitate the chemoselective reduction of an extremely unreactive lactam in the presence of a readily reduced lactone.",10.1021/ja406546k,2013-08-21,0.6024161926732303
Synlett,"Tetrahydrofuran Ring Construction through Tandem Iodocyclizations: Synthesis of Hagen’s Gland Lactones, a Pheromone of Idea leuconoe, an Oxylipid, and Related Compounds","Abstract A simple and efficient common route was developed for the syntheses of tetrahydrofuran-ring-containing natural products such as Hagen’s gland lactones and their epimers, a pheromone of the butterfly Idea leuconoe, an oxylipid, and some valuable synthons. Brown’s allylation, cross-metathesis, iodocyclization, and a tandem aminoxylation/allylation were employed as key steps in the syntheses.",10.1055/a-2550-1785,2025-03-03,0.602409565494817
Tetrahedron,A synthetic protocol for (−)-ketorolac; development of asymmetric gold(I)-catalyzed cyclization of allyl alcohol with pyrrole ring core,,10.1016/j.tetlet.2019.151564,2019-12-24,0.6024023271710505
Tetrahedron,Cylindrol A: A Novel Inhibitor of Ras Farnesyl-Protein Transferase from Cylindrocarpon lucidum,,10.1016/00404-0399(50)0896k-,1995-07-10,0.6024016417845629
Tetrahedron,Cylindrol A: A novel inhibitor of Ras farnesyl-protein transferase from Cylindrocarpon lucidum,,10.1016/0040-4039(95)00896-k,1995-07-01,0.6024016417845629
Journal of the American Chemical Society,Dysidiolide:  A Novel Protein Phosphatase Inhibitor from the Caribbean Sponge <i>Dysidea etheria </i>de Laubenfels,,10.1021/ja961961+,1996-01-01,0.6024016417845629
Tetrahedron,Fusidienol: A novel inhibitor of Ras farnesyl-protein transferase from Fusidium griseum,,10.1016/s0040-4039(00)76943-7,1994-07-01,0.6024016417845629
Journal of Organic Chemistry,A Short Asymmetric Synthesis of (+)-Lyoniresinol Dimethyl Ether,"A short, efficient synthesis of the lignan (+)-lyoniresinol dimethyl ether is described. The synthesis is achieved by asymmetric photocyclization of an achiral dibenzylidenesuccinate to a chiral aryldihydronaphthalene. (-)-Ephedrine is used as a chiral auxiliary to bias the atropisomeric equilibrium in the dibenzylidenesuccinate prior to the photochemical reaction. The synthesis of the title compound was accomplished in five steps, and the final product was recrystallized to constant melting point and rotation.",10.1021/jo0497454,2004-05-20,0.6023983951107156
Tetrahedron,Stereo- and regio-selective Ti-mediated radical cyclization of epoxy-alkenes: synthesis of the A and C ring synthons of paclitaxel,,10.1016/s0040-4039(01)01655-0,2001-10-01,0.6023827821918732
Synlett,The Rhodium Carbenoid Route to 3-Aryl-4-hydroxycoumarins: Synthesis of Derrusnin,All articles of this category (opens in new window),10.1055/s-2005-864808,2005-03-23,0.6023767062051846
Angewandte Chemie International Edition,Highly Efficient Stereocontrolled Total Synthesis of (+)‐Upial,"Dual benefit:(+)-Upial, isolated from the sponge Dysidea fragilis (Kaneohe Bay, Hawaii), as a nonisoprenoid sesquiterpene aldehyde lactone, was efficiently synthesized. The key step involved an intramolecular carbonyl–ene reaction, in which the stereocontrolled construction of a bicyclo[3.3.1]nonane ring with five asymmetric carbon centers and the facile introduction of the exo-methylene unit were achieved in a single step (see scheme).",10.1002/anie.200704423,2007-11-12,0.6023736324799243
Journal of the American Chemical Society,Synthesis of the <i>Leishmania</i> LPG Core Heptasaccharyl <i>myo</i>-Inositol,"Total synthesis of the core heptasaccharyl myo -inositol, Gal p (α1−6)Gal p (α1−3)Gal f (β1−3)[Glc p (α1-PO 4 -6)Man p ](α1−3)Man p (α1−4)GlcN p (α1−6)Ins-1-PO 4, and the corresponding hexasaccharyl myo -inositol, Gal p (α1−6)Gal p (α1−3)Gal f (β1−3)Man p (α1−3)Man p (α1−4)GlcN p (α1−6)Ins-1-PO 4, found in the lipophosphoglycans of Leishmania parasites are described. The target molecules contain synthetic challenges such as an unusual internal galactofuranosyl residue and an anomeric phosphodiester. The synthesis was accomplished using a convergent block synthetic strategy. Four building blocks, a trigalactoside, a dimannoside, a glucosyl inositolphosphate, and a glucosyl-α-1-H-phosphonate, all appropriately protected, were used. The trigalactoside was linked to the dimannoside followed by glycosylation with the glucosyl inositolphosphate to produce the fully protected hexasaccharyl myo -inositol. Subsequent oxidative coupling of the glucosyl-H-phosphonate formed the anomeric phosphodiester linkage to produce the protected heptasaccharyl myo -inositol. Both the assembly order of the subunits and sequence of deprotection were essential for the successful synthesis of these complex molecules. The deprotection was accomplished by deacetylation and clevage of benzyl ethers with sodium in liquid ammonia, followed by acidic deacetalization/desilylation to produce the target molecules.",10.1021/ja001515t,2000-10-27,0.6023731907095221
Tetrahedron,"Evaluation of a synthetic route to ε-viniferin based on a new method for the stereoselective preparation of 2,3-diaryl-2,3-dihydrobenzofurans",,10.1016/0040-4039(94)88313-0,1994-03-01,0.6023709646858095
Organic Process Research & Development,"Merging Biocatalysis, Flow, and Surfactant Chemistry: Innovative Synthesis of an FXI (Factor XI) Inhibitor",The scalable synthesis of an FXI (Factor XI) inhibitor employing multiple emerging technologies is described. The reduction of ketone to chiral alcohol was established through a biocatalysis approach. The Suzuki–Miyaura cross-coupling reaction was facilitated by surfactant chemistry. A harsh hydrolysis of the nitrile was performed in a continuous manufacturing mode. Extensive reaction optimization and process development led to a well-controlled protocol for scale-up. The alternative approach described here addressed issues from the discovery route and was utilized to deliver the desired target for preclinical studies.,10.1021/acs.oprd.0c00412,2020-11-09,0.6023700153553452
Tetrahedron,A new versatile route to 3-hydroxypyrroles,,10.1016/s0040-4039(00)96519-5,1987-01-01,0.602363159595961
Tetrahedron,"[1]Benzopyrano[2,3,4-i,j]isoquinolines: a new, versatile route from 1-bromoxanthones",,10.1016/s0040-4039(01)00983-2,2001-07-01,0.602363159595961
Tetrahedron,Nitrate ester derivatives from epoxides using CAN: Efficient preparation of key intermediates in the synthesis of 4-alkoxytrinems,,10.1016/s0040-4039(97)00670-9,1997-05-01,0.6023628713832476
Organic Letters,"Stereoselective Synthesis of Deuterated β-Cyclohexenylserine, a Biosynthetic Intermediate of the Salinosporamides","A straightforward, highly stereoselective protocol toward the synthesis of deuterium-labeled (2R,3S,4S)-β-cyclohexenylserine has been developed. Key steps are a Nozaki-Hiyama-Kishi reaction generating the stereogenic centers and a ring-closing metathesis for the construction of the cyclohexenyl ring system. The labeled amino acid was further activated as an SNAc-ester for feeding experiments.",10.1021/ol201120k,2011-05-26,0.6023543243240029
Tetrahedron,A catalytic enantioselective synthetic route to the important antidepressant sertraline,,10.1016/s0040-4039(00)73503-9,1994-07-01,0.6023469002612776
Journal of the American Chemical Society,Nazarov Cyclization Initiated by Peracid Oxidation: The Total Synthesis of (±)-Rocaglamide,"The total syntheses of aglafolin, rocagloic acid, and rocaglamide using Nazarov cyclization are described. Generation of the necessary oxyallyl cation intermediate was accomplished via peracid oxidation of an allenol ether to generate an unusual oxycarbenium ion species that undergoes cyclization. The synthesis is efficient, highly diastereoselective, and strategically distinct from previous syntheses of rocaglamide.",10.1021/ja9029736,2009-05-15,0.6023430534617241
Tetrahedron,A practical one-pot process for α-amino aryl ketone synthesis,,10.1016/j.tetlet.2005.09.183,2005-10-21,0.6023421179939745
Tetrahedron,A stereoselective route to bioactive nucleotide phosphonate analogs,,10.1016/j.tetlet.2003.09.071,2003-10-15,0.6023350484478567
Journal of the American Chemical Society,Total Synthesis of Marine Glycosphingolipid Vesparioside B,"The first total synthesis of a major component of marine glycolipid vesparioside B ( Scheme 1 , 1, R1 = n-C22H45, R2 = n-C14H29) has been accomplished through a convergent [4 + 3] coupling strategy. Key steps included stereoselective installment of a set of challenging 1,2-cis-glycoside bonds. A 2-quinolinecarbonyl-assisted α-galactosylation and a novel β-arabinosylation were developed, respectively, to synthesize the α-galactofuranosidic and the β-arabinopyranosidic linkages. Furthermore, a 4,6-O-benzylidene-controlled α-galactopyranosylation reaction allowed the efficient connection of the left tetrasaccharide donor 2 with the right disaccharide lipid acceptor 3, hence leading to the total synthesis of 1.",10.1021/jacs.5b12589,2016-01-19,0.6023325863862454
Angewandte Chemie International Edition,Asymmetric Total Synthesis of Fluvirucinine A1,"Diastereoselective vinyl addition to an amide carbonyl group and amide enolate induced aza-Claisen rearrangement are the key steps in the first asymmetric total synthesis of fluvirucinine A(1) (1), the aglycon of fluvirucin A(1). Fluvirucins are a class of macrolactam antibiotics produced by actinomycete strains that show promising biological properties.",10.1002/(sici)1521-3773(19991203)38:23<3545::aid-anie3545>3.0.co;2-0,1999-11-30,0.6023315144086426
Angewandte Chemie International Edition,Asymmetric Total Synthesis of Fluvirucinine A1,"Diastereoselective vinyl addition to an amide carbonyl group and amide enolate induced aza-Claisen rearrangement are the key steps in the first asymmetric total synthesis of fluvirucinine A1 (1), the aglycon of fluvirucin A1. Fluvirucins are a class of macrolactam antibiotics produced by actinomycete strains that show promising biological properties.",10.1002/(sici)1521-3773(19991203)38:23<3545::aid-anie3545>3.3.co;2-s,1999-12-03,0.6023315144086426
Organic Letters,Scalable Total Synthesis of (+)- and (−)-Codonopiloneolignanin A via Ti(IV)/NHC Cooperative Control Highly Enantioselective Dimerization of Multisubstituted Cinnamaldehyde,"The first gram-scale asymmetric total synthesis of (+)- and (−)-codonopiloneolignanin A has been achieved from multisubstituted cinnamaldehyde in four steps with 37% overall yield. The synthetically challenging tricyclic [5, 3, 0, 0 3,8 ] decane skeleton was efficiently constructed via a highly enantioselective dimerization of multisubstituted cinnamaldehyde, followed by a sequence of cascade reactions including Prins cyclization, cation mediated cyclization, and deprotection. Furthermore, the scope of NHC-catalyzed/Ti(IV)-mediated synergistic control multisubstituted cinnamaldehyde dimerization was investigated. Significantly, the bioactivity of codonopiloneolignanin A and its enantiomer, particularly scarce in nature, was tested and showed good anticancer activity.",10.1021/acs.orglett.1c02408,2021-07-29,0.6023280814949722
Synlett,Synthesis of Indole Phytoalexins Brassinin and Cyclobrassinin <i>via</i> [1-(<i>tert</i>-Butoxycarbonyl)indol-3-yl]-methyl Isothiocyanate as the Key Biomimetic Intermediate,All articles of this category A four-step synthesis of 1-protected indol-3-ylmethyl isothiocyanates from indole-3-carboxaldehyde has been elaborated. [1-( tert -Butoxycarbonyl)indol-3-yl]-methyl isothiocyanate appeared to be a suitable biomimetic intermediate for the synthesis of protected phytoalexins brassinin and cyclobrassinin. Removing of the tert -butoxycarbonyl protecting group under specific conditions afforded phytoalexins identical with previously described compounds. indole phytoalexins - brassinin - cyclobrassinin - isothiocyanate - biomimetic,10.1055/s-1997-761,1997-03-01,0.6023258482585849
Synlett,Synthesis of Pentafluorosulfanyl-Containing Indoles and Oxindoles,"Vicarious nucleophilic substitution (VNS) of 3- and 4-nitro(pentafluorosulfanyl)benzenes with phenoxyacetonitrile followed by catalytic hydrogenation provided a two-step, atom-economical synthetic route to 6- and 5-(pentafluoro-sulfanyl)­1 H ­indoles. The VNS reaction with chloromethyl phenyl sulfone, nitro group reduction, imine formation, and base-induced cyclization gave efficient access to 2-aryl substituted 6- and 5-(pentafluorosulfanyl)-1 H -indoles. Finally, the VNS reaction with ethyl chloroacetate and nitro group reduction followed by thermal cyclization (lactam formation) furnished SF 5 -containing oxindoles. Their transformation into 2-halo-substituted SF 5 -indoles was demonstrated.",10.1055/s-0032-1318452,2013-03-07,0.6023201899834647
Tetrahedron,"An efficient route to 1,3-amino hydroxyl system via electrophilic lactonization of 2-amino-4-pentenoic acid derivatives. Stereoselective synthesis of (−)-bulgecinine",,10.1016/s0040-4039(00)85403-9,1986-01-01,0.6023188491767372
Tetrahedron,N-acyldihydropyridones as synthetic intermediates. A short synthesis of (±)-indolizidine 209B.,,10.1016/s0040-4039(00)79418-4,1991-10-01,0.602317930092398
Tetrahedron,N-acyldihydropyridones as synthetic intermediates. A short synthesis of (±)-pumiliotoxin C.,,10.1016/s0040-4039(00)93533-0,1991-10-01,0.602317930092398
Synlett,"Synthetic Studies of Halichondrin B, an Antitumor Polyether Macrolide Isolated from a Marine Sponge. 3. Synthesis of C27-C36 Subunit<i>via</i>Completely Stereoselective<i>C</i>-Glycosylation to the F Ring",All articles of this category A stereoselective synthesis of the C27-C36 fragment of halichondrin B starting from L-tartaric acid using an efficient acidcatalyzed C -glycosylation to the F ring as the key step is reported.,10.1055/s-1994-22732,1994-01-01,0.6023119622287001
Synthesis,Efficient Synthesis of Imidazole-Fused Benzodiazepines Using Palladium-Catalyzed Intramolecular C–N Bond Formation Reaction,An efficient three-step synthetic route to imidazole-fused benzodiazepines from imidazole-2-carbaldehyde is described. Application of intramolecular Buchwald–Hartwig cycloamination reaction in the final step is shown to be a convenient method for the synthesis of fused seven-membered diazacycles. The reactions proceeded smoothly with both aliphatic and aromatic amines.,10.1055/s-0032-1316828,2012-12-06,0.6023114503393605
Journal of Organic Chemistry,First Total Synthesis of Leucamide A,"The first total synthesis of marine bioactive cyclic heptapeptide Leucamide A has been accomplished, including a simple method for construction of the 4,2-bisheterocycle tandem pair substructure that employs a DAST-mediated cyclization of beta-hydroxy amide and final HBTU-promoted ring closing.",10.1021/jo026799+,2003-01-23,0.6022985216386118
Synthesis,"One-Pot Synthesis of Substituted Isothiazol-3(2<i>H</i>)-ones: Intramolecular Annulation of α-Carbamoyl Ketene-<i>S</i>,<i>S</i>-acetals via PIFA-Mediated N-S Bond Formation","A facile and efficient synthetic route towards highly substituted isothiazol-3(2H)-ones 2 from readily available α-carbamoyl ketene-S,S-acetals 1 is presented. The key step features the formation of an N-acylnitrenium ion, generated from the oxidization of substituted amides with the hypervalent iodine reagent phenyl­iodine(III) bis(trifluoroacetate) (PIFA), and its succeeding intra­molecular amidation to form a new N-S bond affording the title compounds.",10.1055/s-2007-983875,2007-09-01,0.6022933209373178
Journal of Organic Chemistry,Stereoselective Synthesis of the C31−C40/C43−C52 Unit of Amphidinol 3,"A concise synthesis of a tetrahydropyran ring system corresponding to the C31-C40 and C43-C52 units of amphidinol 3 is described. Successive chemoselective reactions, i.e., cross-metathesis to differentiate the iodoolefin from the terminal olefin and Sharpless asymmetric dihydroxylation on the resulting E-olefin, resulted in expeditious synthesis of an intermediate that was then cross-coupled to afford an E,E-diene system. Four contiguous stereogenic centers were installed via construction of the tetrahydropyran ring by means of Katsuki-Sharpless asymmetric epoxidation, 6-endo-tet cyclization, and Sharpless asymmetric dihydroxylation.",10.1021/jo901793f,2009-10-23,0.6022913875134808
Tetrahedron,Synthesis of the fully functionalized tris-oxazole fragment found in metabolites derived from marine organisms,"The synthesis of the fully functionalized tris-oxazole fragment 9 found in marine metabolites kabiramide C and halichondramide is reported employing modified Hantzsch methodology. Starting with the condensation reaction between cinnamamide 1 and ethyl bromopyruvate 2, the synthetic sequence leading to 9 was carried out in 13 steps with an overall yield of 26%.",10.1016/s0040-4039(97)01218-5,1997-08-01,0.6022888702912441
European Journal of Organic Chemistry,Asymmetric Synthesis of (S)-β2-Homoarylglycines,The synthesis of racemic N-phthalyl β2-homoarylglycines 5 and their asymmetric transformation have been investigated. The key step is the stereoselective addition of the (R)-pantolactone to the corresponding prochiral ketene 7.,10.1002/1099-0690(200007)2000:13<2459::aid-ejoc2459>3.0.co;2-d,2000-07-01,0.6022868801583335
Tetrahedron,A vinylogous urethane approach towards the synthesis of okadaic acid. Construction of the C1-C8 fragment. Part I,"A vinylogous urethane approach is utilized to synthesize the Cl-C8 fragment of okadaic acid. The key steps include an asymmetric alkylation, a hydroxyl directed iodocarbonate cyclization and a stereoselective cyanohydrin formation.",10.1016/s0040-4039(98)00971-x,1998-07-01,0.6022827035257068
Organic Letters,A Pot-Economical Approach to the Total Synthesis of Sch-725674,"A pot-economical total synthesis of antifungal Sch-725674, 1, is reported. The approach takes advantage of a number of one-pot, sequential transformations, including a phosphate tether-mediated one-pot, sequential RCM/CM/chemoselective hydrogenation protocol, a one-pot tosylation/acrylation sequence, and a one-pot, sequential Finkelstein reaction/Boord olefination/acetonide deprotection procedure to streamline the synthesis route by reducing isolation and purification procedures, thus saving time. Overall, an asymmetric route has been developed that is efficiently accomplished in seven pots from phosphate (S,S)-triene and with minimal purification.",10.1021/acs.orglett.5b03547,2016-01-13,0.6022786310316111
Journal of Organic Chemistry,Total Synthesis of Tricolorin A,"Tricolorin A (1), a structurally amazing resin glycoside with promising bioactivities from Ipomoea tricolor cav. (convolvulaceae), was synthesized in a total of 45 steps, with the longest linear sequence of 20 steps and overall yield of 0.65% from D-mannitol. The AB disaccharide 19-membered lactone 2 was constructured by a regioselective macrolactonization using Corey-Nicolaou protocol. The macrolactone tetrasaccharide 33 was realized either by ""one-pot two-step"" glycosylation procedure or by a stepwise assembly employing the ""armed-disarmed"" glycosylation strategy.",10.1021/jo9711450,1997-11-01,0.6022747362573982
Tetrahedron,"Motuporin, A Potent Protein Phosphatase Inhibitor Isolated from the Papua New Guinea Sponge Theonella swinhoei Gray",,10.1016/s0040-4039(00)91674-5,1992-03-01,0.6022622967447778
Organic Letters,Expeditious Synthesis of Phenanthrenes via CuBr<sub>2</sub>-Catalyzed Coupling of Terminal Alkynes and <i>N-</i>Tosylhydrazones Derived from <i>O</i>-Formyl Biphenyls,A new method for the synthesis of phenanthrenes via ligand-free CuBr(2)-catalyzed coupling/cyclization of terminal alkynes with N-tosylhydrazones derived from o-formyl biphenyls has been developed. This new synthesis has wide range of functional group compatibility.,10.1021/ol201788v,2011-08-29,0.602261731193739
Organic Letters,Synthesis of Spongidine A and D and Petrosaspongiolide L Methyl Ester Using Pyridine C–H Functionalization,An efficient strategy for the synthesis of the potent phospholipase A 2 inhibitors spongidine A and D is presented. The tetracyclic core of the natural products was assembled via an intramolecular hydrogen atom transfer initiated Minisci reaction. A divergent late-stage functionalization of the tetracyclic ring system was also used to achieve a concise synthesis of petrosaspongiolide L methyl ester.,10.1021/acs.orglett.9b04315,2019-12-26,0.6022604160131124
Organic Process Research & Development,New Synthesis of a Protected Ketonucleoside by a Non-Cryogenic Oxidation with TFAA/DMSO<sup>1</sup>,"An improved synthesis of the ketonucleoside 2‘-Oxo-3‘,5‘- O -[1,1,3,3-tetrakis(1-methylethyl)-1,3-disiloxanediyl]-cytidine ( 6 ), an intermediate in the synthesis of the potent anti-tumor agent 1 (MDL 101,731 or FMdC), is reported which incorporates a trifluoroacetic acid/dimethylsulfoxide oxidation process. This oxidation procedure eliminates the cryogenic reaction conditions and the necessity of protection at the N-4 amine used in the previously published route. Simplified isolation procedures for 3 and 4 eliminate two chromatographic purification steps. Overall yields are comparable to those reported previously.",10.1021/op9900939,2000-04-08,0.6022593941576619
Tetrahedron,"An improved synthesis of the strained pyrrolidine-5,5-translactam ring system",,10.1016/s0040-4039(99)00365-2,1999-04-01,0.6022387332295133
Synlett,"Stereoselective Total Synthesis of (+)-Goniothalesdiol and (+)-2,5-<i>epi</i>-Goniothalesdiol from <scp>d</scp>-Mannitol","An efficient and practical total synthesis of (+)-gonio­thalesdiol and its 2,5-epi analogue is described herein. The key ­features include a diastereoselective reduction of C-5 keto with Zn(BH4)2 to generate the desired stereochemistry at C-5. The tetra­hydrofuran backbone of natural goniothalesdiol was synthesized under basic conditions via epoxide formation, followed by in situ 5-exo opening of the epoxide ring with γ-benzoyloxy oxygen upon ­debenzoylation. For the 2,5-epi analogue, the tetrahydrofuran ring was formed via acid-catalyzed acetonide deprotection followed by concomitant SN2 displacement of the O-mesyl group at C-5 center with C-2-γ-oxygen.",10.1055/s-2007-980351,2007-05-23,0.6022384471440351
Angewandte Chemie International Edition,Total Synthesis of (+)‐Neopeltolide,"Rapid elaboration: (+)-Neopeltolide, a novel marine metabolite with potent cytotoxicity against several cancer cell lines, was the target of an efficient total synthesis (see scheme). The construction of the 2,4,6-trisubstituted tetrahydropyran substructure is based on a Suzuki–Miyaura coupling/ring-closing metathesis sequence. BOM=benzyloxymethyl, MPM=4-methoxyphenylmethyl, TIPS=triisopropylsilyl.",10.1002/anie.200801399,2008-05-19,0.6022294521046088
Organic Letters,An Asymmetric Aminohydroxylation Approach to the Azepine Core of (−)-Balanol,"[reaction: see text]An efficient formal synthesis of the potent protein kinase C inhibitor (-)-balanol that relies on a modified asymmetric aminohydroxylation of the alpha,beta-unsaturated aryl ester (1) is reported. The aryl ester functionality and the dihydroquinyl alkaloid ligand system (DHQ)2-AQN are used to control the regio- and enantioselectivity of the process.",10.1021/ol0061034,2000-07-26,0.6022274483568998
Tetrahedron,Synthesis of bastadin analogs through an SNAr coupling strategy,,10.1016/s0040-4039(02)02378-x,2002-12-01,0.6022270955203775
Tetrahedron,Efficient two-step synthesis of methylphytylbenzoquinones: precursor intermediates in the biosynthesis of vitamin E,,10.1016/s0040-4039(02)02564-9,2003-01-01,0.602217813716689
Synlett,"Synthetic Study on Carthamin, Part 4. Improved Synthesis of a C-Glycosyl Quinochalcone by Installation of a Side Chain through Regioselective De-O-methylation and Acyl Rearrangement","Abstract We report an improved synthesis of a C-Glycosyl quinochalcone that is a key intermediate in our total synthesis of carthamin, a natural red pigment of traditional heritage. The C-glycosyl quinochalcone is prepared by regioselective de-O-methylation of a C-glycosyl bromodienone, and installation of a p-coumaroyl side chain through an O→C acyl rearrangement.",10.1055/s-0040-1719836,2021-09-21,0.6022060595578782
Organic Letters,Enantioselective Spirocyclizations from Tryptophanol-Derived Oxazolopiperidone Lactams,"A straightforward synthetic route to enantiopure spiro[indole-3,3'-indolizidines] is reported. The key step is a Lewis acid promoted cyclization of a Na-tosyltryptophanol-derived oxazolopiperidone lactam in the presence of Et3SiH.",10.1021/ol0712327,2007-06-29,0.6022023238403239
Tetrahedron,"Studies toward the total synthesis of cyclodidemniserinol trisulfate. Part I: 3,5,7-Trisubstituted 6,8-dioxabicyclo [3.2.1] octane core structure construction via a convergent and a linear stereoselective synthesis",,10.1016/j.tetlet.2009.05.102,2009-05-31,0.6022021596291984
Synlett,Development of a New Nonsugar-Based Strategy for the Synthesis of the Hydroxylated Indolizidinone Skeleton,"The diastereocontrolled formation of the polyhydroxylated indolizidinone skeleton from linear alkynylamides is achieved by the sequential combination of two key cyclization steps. In particular, a PIFA-mediated intramolecular alkyne amidation reaction affords the 5-alkenoylpyrrolidinone skeleton, whereas a subsequent Ru-catalyzed ring-closing-metathesis protocol assembles the bicyclic indolizidine framework. Manipulation of the ketone carbonyl group, developed in the former cyclization step under controlled reductive conditions, and oxidation of the C6-C7 double bond, generated in the latter one under Upjohn conditions, fix the 6,7,8-trihydroxy groups in a complete diastereoselective manner.",10.1055/s-0031-1290604,2012-02-28,0.6022018577195852
Tetrahedron,A novel approach to the synthesis of enediynes,,10.1016/0040-4039(91)80759-y,1991-10-01,0.6021875612060976
Tetrahedron,"A novel approach towards 2,3-dideoxyriboside synthesis",,10.1016/s0040-4039(00)60562-2,1993-01-01,0.6021875612060976
Tetrahedron,A novel approach to the synthesis of prostanoids,,10.1016/s0040-4039(00)72680-3,1975-01-01,0.6021875612060976
Tetrahedron,A novel approach to the synthesis of symmetrical and unsymmetrical porphyrin dimers,,10.1016/s0040-4039(00)79081-2,1992-09-01,0.6021875612060976
Tetrahedron,A novel approach to synthesis of tricyclic diterpenoid,,10.1016/j.tetlet.2004.02.136,2004-03-20,0.6021875612060976
Tetrahedron,A novel approach for the synthesis of (S)-tolvaptan and (S)-desmethyltolvaptan,,10.1016/j.tetlet.2024.155245,2024-08-10,0.6021875612060976
Synthesis,Scalable Synthesis of Strained Cyclooctyne Derivatives,"Modifications to the Popik synthesis of aza-dibenzocyclooctyne (DIBAC) derivatives are described, which avoids tedious purifications and dramatically improves the yield. A new and analogous route to biarylazacyclooctynone (BARAC) through an amide disconnection was also attempted. The BARAC derivatives prepared were found to be unstable under the conditions employed, undergoing a known rearrangement. Finally, the synthesis of a difluoro-DIBAC derivative with a second-order rate constant intermediate between DIBAC and BARAC derivatives (0.50 M–1) is described. While more difficult to synthesize, this molecule was found to be considerably more stable than any BARAC derivatives that were prepared.",10.1055/s-0033-1340509,2014-01-10,0.6021796203712552
Organic Letters,Total Synthesis of (−)-Exiguolide,"The first total synthesis of the naturally occurring enantiomer of exiguolide ((-)-1) has been completed. This very convergent synthesis features the following as main steps: (i) a Trost's ruthenium-catalyzed ene-yne cross-coupling reaction (this complex transformation allows the challenging control of the C5-C28 double bond geometry along with the stereoselective construction of the tetrahydropyran ring A) and (ii) a very efficient one-pot, two-step stereoselective conjugated allylic alcohol substitution that allowed the control of the C15 stereogenic center.",10.1021/ol902829e,2010-01-15,0.6021712240279393
Journal of Organic Chemistry,A Cross-Metathesis Route to the 5-F<sub>2</sub>-Isoprostanes,"A library of eight 5-F(2)-isoprostanes was prepared through a ring-opening metathesis/cross-metathesis protocol between functionalized bicyclo[3.2.0]heptenes, ethylene, and alpha,beta-unsaturated ketones. This sequence provided racemic enones in a regio- and stereoselective fashion that could be converted to enantiomerically enriched allylic alcohols through a catalyst-controlled asymmetric reduction. Completion of the sidechains, followed by global deprotection, resulted in a stereodivergent route to eight enantiomerically enriched 5-F(2)-isoprostanes. Overall, the synthesis of this library of known and anticipated lipid oxidation metabolites was achieved in 10 steps from commercially available 4-hydroxy-2-cyclopentenone.",10.1021/jo702702s,2008-04-17,0.6021691364582747
Organic Letters,"Catalytic Asymmetric Synthesis of Phthioceranic Acid, a Heptamethyl-Branched Acid from <i>Mycobacterium tuberculosis</i>","The first total synthesis of phthioceranic acid (1) has been achieved by an iterative catalytic asymmetric 1,4-addition protocol. This method provides a robust and high-yielding route for the preparation of 1,3-oligomethyl (deoxypropionate) arrays. After the desired number of methyl groups has been introduced, these arrays can be further functionalized at both ends to polymethyl-substituted lipids such as phthioceranic acid, a heptamethyl-branched fatty acid from the virulence factor Sulfolipid-I (2), found in Mycobacterium tuberculosis.",10.1021/ol071078o,2007-07-14,0.6021622320910139
Organic Process Research & Development,"Practical Synthesis of an Orally Active CCR5 Antagonist, 7-{4-[2-(Butoxy)- ethoxy]phenyl}-<i>N</i>-(4-{[methyl(tetrahydro-2<i>H</i>-pyran-4-yl)amino]methyl}phenyl)- 1-propyl-2,3-dihydro-1<i>H</i>-1-benzazepine-4-carboxamide","A practical method of synthesizing 7-{4-[2-(butoxy)ethoxy]phenyl}- N -(4-{[methyl(tetrahydro-2 H -pyran-4-yl)amino]methyl}phenyl)-1-propyl-2,3-dihydro-1 H -1-benzazepine-4-carboxamide ( 8 ), an orally active CCR5 antagonist, has been developed. Methyl 7-bromo-1-propyl-2,3-dihydro-1 H -1-benzazepine-4-caboxylate ( 14a ) was synthesized in good yield by the esterification of 4-[(4-bromo-2-formylphenyl)(propyl)amino]butanoic acid ( 13 ) followed by an intramolecular Claisen type reaction with 28% sodium methoxide in dimethyl carbonate as a solvent in one pot. The Suzuki−Miyaura reaction of 14a and 1-bromo-4-(2-butoxyethoxy)benzene ( 10 ) followed by hydrolysis and amidation gave 8 . A new inexpensive method without chromatographic purification was established.",10.1021/op0497916,2005-02-03,0.6021589850500839
Tetrahedron,Synthetic applications of masked o-benzoquinones. A novel total synthesis of (±)forsythide aglucone dimethyl ester,,10.1016/s0040-4039(00)99662-x,1989-01-01,0.6021567167534544
Journal of the American Chemical Society,"A Novel and General Synthetic Pathway to Strychnos Indole Alkaloids:  Total Syntheses of (−)-Tubifoline, (−)-Dehydrotubifoline, and (−)-Strychnine Using Palladium-Catalyzed Asymmetric Allylic Substitution","A method of palladium-catalyzed asymmetric allylic substitution for synthesizing 2-substituted cyclohexenylamine derivatives was established. Treatment of a 2-silyloxymethylcyclohexenol derivative with ortho-bromo-N-tosylaniline in the presence of Pd(2)dba(3).CHCl(3) and (S)-BINAPO in THF afforded a cyclohexenylamine derivative with 84% ee in 80% yield. The Heck reaction was carried out to produce an indolenine derivative in good yield. Using this method, we synthesized indolenine derivative 7, which was recrystallized from EtOH to give an optically pure compound. From this compound, tetracyclic ketone 13, which should be a useful intermediate for the synthesis of indole alkaloids, could be synthesized. The total syntheses of (-)-dehydrotubifoline, (-)-tubifoline, and (-)-strychnine were achieved from 13. All ring constructions for the syntheses of these natural products were achieved using a palladium catalyst.",10.1021/ja029382u,2003-07-17,0.6021537065286863
Synthesis,Improved Synthesis of Lycoricidine Triacetate,"All articles of this category The synthesis of lycoricidine triacetate by a modified pathway is described. In this preparation, catalytic amounts of osmium tetroxide are used to stereospecifically introduce two hydroxy groups, rendering the title compound via two novel intermediates.",10.1055/s-1987-28056,1987-01-01,0.6021530857046048
Angewandte Chemie International Edition,Total Synthesis of Jadomycin A and a Carbasugar Analogue of Jadomycin B,"One's trash is another one's treasure: The first syntheses of jadomycin A and the carbasugar analogue of jadomycin B have been achieved in 6 and 20 longest linear steps, respectively. The key ring system of the aglycone was prepared by a 6π-electron electrocyclic ring closure and subsequent hemiaminal ring closure. Acid sensitivity of the glycosidic bond in jadomycin B (see structure; X=O) precluded its synthesis but led to the carbasugar analogue (X=CH2).",10.1002/anie.201005329,2010-10-26,0.6021448811091384
Synlett,The Application of <i>tert</i>-Butanesulfinamide in the AsymmetricSynthesis of the Core Structure of Polyoxin and Nikkomycin Antibiotics,"A stereoselective approach to the core structure of polyoxin and nikkomycin antibiotics has been developed. The key steps of this approach include diastereoselective nucleophilic addition of 2-lithioftiran to tert-butanesulfinyl imine derived from (s)-tert-butanesulfinamide and ribosyl aldehyde for the generation of C-5 stereocenter, and the use of triflic acid to remove tert-butylsulfonyl group. Significantly, the synthesis provides a method for large-scale preparation of polyoxin and nikkomycin analogues because of simple operation, excellent yield and high stereoselectivity.",10.1055/s-0028-1087949,2009-02-24,0.6021446684099305
Angewandte Chemie International Edition,Cover Picture: Total Synthesis and Antitumor Activity of ZK‐EPO: The First Fully Synthetic Epothilone in Clinical Development (Angew. Chem. Int. Ed. 47/2006),"Nature is a brilliant architect for the design of compounds with interesting biological functions. Epothilone B (top), a metabolite of myxobacteria (fruiting body in background), served as the lead structure for the development of an anticancer drug candidate. Optimization efforts led to ZK‐EPO (bottom) as a candidate for clinical development. ZK‐EPO has an improved therapeutic window and is not recognized by multidrug‐resistance efflux pumps. Its total synthesis starting from simple compounds (blue) is described by U. Klar et al. on page 7942 ff.",10.1002/anie.200690162,2006-11-27,0.6021410749108871
Synlett,"Synthesis of 6-Chloro-5-(trifluoroacetyl)pyridine-3-carbonitrile: A Novel, Versatile Intermediate for the Synthesis of Trifluoromethylated Azaindazole Derivatives","A synthesis of 6-chloro-5-(trifluoroacetyl)pyridine-3-carbonitrile, a versatile building block for the synthesis of trifluoromethylated N-heterocycles, is described. The reactions of 6-chloro-5-(trifluoroacetyl)pyridine-3-carbonitrile with 1,2- and 1,3-bisnucleophiles were investigated.",10.1055/s-0037-1611815,2019-05-02,0.6021374297888183
Organic Letters,Stereoselective Synthesis of (−)-Verazine and Congeners via a Cascade Ring-Switching Process of Furostan-26-acid,"An efficient synthetic strategy for three natural seco -type cholestane alkaloids isolated from the Veratrum plants, based on commercially available naturally occurring and abundant (−)-diosgenin ( 1 ), as exemplified in the concise asymmetric synthesis of (−)-verazine ( 4 ), (−)-veramiline ( 5 ) (proposed structure), and its 22-epimer, (−)-oblonginine ( 6 ), is presented. This work highlights the application of a cascade ring-switching process of (−)-diosgenin to achieve the E-ring opening and construction of chiral six-membered lactone challenges in seco -type cholestane alkaloid synthesis. This approach enables the synthesis of related natural and nature-like novel cholestane alkaloids, opening up opportunities for more extensive exploration of cholestane alkaloid biology.",10.1021/acs.orglett.0c00747,2020-03-23,0.6021330456944717
Journal of Organic Chemistry,High-Yielding Synthesis of Sphingoid-Type Bases,"An efficient methodology for the synthesis of sphingoid-type bases is reported. It involves the stereoselective addition of a racemic 3-alkoxy allenylzinc to enantiopure N-tert-butylsulfinyl imines and a cross-metathesis reaction as the key steps. It has been successfully applied to the syntheses of sphinganine and naturally occurring bioactive related compounds, among which the hydrolysis product of clavaminol H and two spisulosines. All of these compounds have been prepared in six steps from N-tert-butylsulfinyl imines in high overall yields (>56%).",10.1021/jo901567q,2009-08-12,0.60213240736084
Synlett,An Expeditious Route to GlcNAc-Cbz-Asn by Chemo-enzymatic Synthesis,"A short-step route to GlcNAc-Cbz-Asn was developed. Treatment of GlcNAc in sat. aq. NH4HCO3 solution and subsequent electorodialytic desalting provided ammonia-free glycosylamine in large quantity. The product was coupled with Cbz-Asn α-isobutyl ester β-fluoride, and finally, the isobutyl ester was deprotected by enzyme-catalyzed hydrolysis under mild conditions.",10.1055/s-2002-19355,2002-01-01,0.6021310073882855
Journal of Organic Chemistry,Synthetic Efforts and Ultimate Limitation to an Asymmetric Achmatowicz Approach Toward EBC-23,"An effort toward the total synthesis of the polyketide natural product EBC-23 is reported. The asymmetric approach is convergent and uses a late-stage Claisen-like enolate/acid chloride coupling to establish a key 1,3-diketone intermediate. The 1,3-diketone target is an oxidized form of the hydrated natural product, which fails to spiroketalize. The convergent asymmetric synthesis uses an asymmetric Noyori transfer hydrogenation of a β-furyl ketoester to enantioselectively form a chiral furyl alcohol. An Achmatowicz/Jones/Luche three-step reaction sequence was used to stereoselectively convert the furyl alcohol into the 5-hydroxy-pyran-2-one. The absolute stereochemistry of the 1,3-polyol fragment was established by a Leighton allylation. A subsequent Grubbs cross-metathesis, and Evans acetalation were used to install the 1,3- syn -diol stereochemistry.",10.1021/acs.joc.2c00262,2022-04-18,0.6021212925456485
Synthesis,Synthesis of an Ambergris-Type Ketal from Abietic Acid,"Abietic acid, the main component of pine rosin, was used as starting material for the hemisynthesis of the ambergris-type ketal. The key intermediate step consisted of the synthesis of an exocyclic olefin through appropriate handling of a very sensitive aldehyde generated as an intermediate precursor.",10.1055/s-2006-926392,2006-01-01,0.6021171226197747
Organic Letters,A New Selective Synthesis of the Ile-<i>a</i><i>llo</i>-Thr-Gly Tripeptide Fragment of Lysobactin,"[formula: see text] trans-Aziridine-2-carboxylic acid derivatives are useful intermediates for the synthesis of threonine or allo-threonine through ring expansion and SN2 displacement, respectively. We describe here the preparation of the Ile-allo-Thr-Gly 11 fragment of Lysobactin via the aziridine 9 intermediate.",10.1021/ol005659o,2000-03-29,0.60211676017067
Synlett,Bridgehead Intermediates in Organic Synthesis Construction of the Tetracyclic Skeleton of Leucothol A,All articles of this category A tetracyclic intermediate for the synthesis of leucothol A can be constructed in seven steps. The key step involves the reaction of pentadienyltributylstannane with a bridgehead radical.,10.1055/s-1994-22808,1994-01-01,0.6021144197872786
Journal of Organic Chemistry,Total Synthesis of (−)-Levesquamide,"The total synthesis of levesquamide, a natural product with an unprecedented pentasubstituted pyridine-isothiazolinone skeleton, has been accomplished from kojic acid for the first time. The key features of the synthesis include a Suzuki coupling reaction between bromopyranone and oxazolyl borate fragments, a copper-mediated introduction of a thioether, a mild hydrolysis of a pyridine 2- N -methoxyamide, and a Pummerer-type cyclization of a tert -butyl sulfoxide to form the key pyridine-isothiazolinone unit of the natural product.",10.1021/acs.joc.2c03066,2023-03-02,0.6021131983707673
Tetrahedron,First asymmetric total synthesis of (+)-curcutetraol,,10.1016/j.tetlet.2008.02.094,2008-02-22,0.6021041387021047
Tetrahedron,Asymmetric total synthesis of (+)-monocerin,,10.1016/j.tetlet.2013.09.055,2013-09-21,0.6021041387021047
Tetrahedron,Asymmetric total synthesis of Lycopodium alkaloid (+)-lycopladine A,,10.1016/j.tetlet.2013.03.097,2013-04-02,0.6021041387021047
Tetrahedron,Asymmetric total synthesis of (S)-dapoxetine,,10.1016/j.tetlet.2012.05.037,2012-05-12,0.6021041387021047
Tetrahedron,Asymmetric total synthesis of curacin A,,10.1016/0040-4039(96)00860-x,1996-06-01,0.6021041387021047
Tetrahedron,Asymmetric total synthesis of 9-methoxystrobilurin K,,10.1016/s0040-4039(01)00812-7,2001-07-01,0.6021041387021047
Tetrahedron,Asymmetric total synthesis of (−)-deoxoprosophylline,,10.1016/s0040-4039(01)00483-x,2001-05-01,0.6021041387021047
Tetrahedron,Asymmetric total synthesis of Tofacitinib,,10.1016/j.tetlet.2013.07.042,2013-07-13,0.6021041387021047
Tetrahedron,Asymmetric induction by sulfinyl chirality. A total synthesis of (+)-talaromycin A and (−)-talaromycin B,,10.1016/s0040-4039(00)96304-4,1987-01-01,0.6021041387021047
Tetrahedron,Asymmetric total synthesis of azasugars branched at C-5,,10.1016/s0040-4039(00)79713-9,1991-07-01,0.6021041387021047
Tetrahedron,"Asymmetric total synthesis of (+)-pisatin, a phytoalexin from garden peas ( Pisum sativum L.)",,10.1016/s0040-4039(98)00299-8,1998-04-01,0.6021041387021047
Tetrahedron,Asymmetric total synthesis of (+)-desoxoprosophylline,,10.1016/s0040-4039(98)02129-7,1998-12-01,0.6021041387021047
Tetrahedron,An asymmetric total synthesis of sanjoinine G1,,10.1016/s0040-4039(98)80025-7,1999-01-01,0.6021041387021047
Tetrahedron,Asymmetric total synthesis of (−)-prosophylline,,10.1016/s0040-4039(99)01387-8,1999-09-01,0.6021041387021047
Tetrahedron,Asymmetric total synthesis of (+)-goniopypyrone,,10.1016/s0040-4039(00)61602-7,1993-10-01,0.6021041387021047
Tetrahedron,Asymmetric total synthesis of buprenorphine and dihydroetorphine,,10.1016/j.tetlet.2022.154027,2022-07-20,0.6021041387021047
Tetrahedron,Asymmetric total synthesis of Sumatranin A,,10.1016/j.tetlet.2025.155785,2025-08-06,0.6021041387021047
Tetrahedron,Asymmetric total synthesis of (−)-deoxypodophyllotoxin,,10.1016/s0040-4039(00)94387-9,1990-01-01,0.6021041387021047
Tetrahedron,Asymmetric total synthesis of phomonol,,10.1016/j.tetlet.2017.06.028,2017-06-14,0.6021041387021047
Tetrahedron,Asymmetric total synthesis of halicholactone,,10.1016/s0040-4039(00)00434-2,2000-05-01,0.6021041387021047
Tetrahedron,Asymmetric total synthesis of alkaloids and seco-iridoids,,10.1016/s0040-4039(00)88908-x,1990-01-01,0.6021041387021047
Tetrahedron,First asymmetric total synthesis of aspinolide A,,10.1016/j.tetlet.2009.09.151,2009-10-02,0.6021041387021047
Angewandte Chemie International Edition,Corrigendum: Asymmetric Total Synthesis of Brasilicardins,,10.1002/anie.202111499,2021-10-18,0.6021041387021047
Tetrahedron,Asymmetric total synthesis of (–)-rossinone A,,10.1016/j.tetlet.2021.153456,2021-10-04,0.6021041387021047
Tetrahedron,Asymmetric total synthesis of (−)-epibatidine,,10.1016/s0040-4039(98)00803-x,1998-06-01,0.6021041387021047
Tetrahedron,Asymmetric total synthesis of antileukemic sesquiterpene (+)-ivalin,,10.1016/s0040-4039(00)99876-9,1984-01-01,0.6021041387021047
Tetrahedron,A total asymmetric synthesis of the isolactarane sesquiterpene (−)-merulidial,,10.1016/s0040-4039(00)61307-2,1992-08-01,0.6021041387021047
Tetrahedron,Asymmetric total synthesis of (−) podophyllotoxin,,10.1016/0040-4039(96)00937-9,1996-07-01,0.6021041387021047
Tetrahedron,An asymmetric total synthesis of (−)-fumagillol,,10.1016/s0040-4039(97)00925-8,1997-06-01,0.6021041387021047
Tetrahedron,The total asymmetric synthesis of Halicholactone and Neohalicholactone,,10.1016/0040-4039(95)00588-4,1995-05-01,0.6021041387021047
Tetrahedron,Asymmetric total synthesis of (+)-sattazolin,,10.1016/j.tetlet.2012.10.124,2012-11-05,0.6021041387021047
Organic Letters,Short Total Synthesis of (+)-Madindolines A and B,"[reaction: see text] A short and efficient total synthesis of (+)-madindolines A (1) and B (2), potent and selective inhibitors of interleukin 6, has been achieved. The synthesis features a key chelation-controlled 1,4-diastereoselective acylation to generate the quaternary carbon and an intramolecular acylation of allylsilane to build up the cyclopentene unit.",10.1021/ol017058i,2002-01-30,0.6020997446845335
Synlett,Diastereoselective Allylation of a Chiral Imine with Allylzinc Reagents: Diastereoselective Synthesis of a Novel Broad Spectrum Carbapenem,"All articles of this category Diastereoselective allylation of chiral imine with allylmetal reagents was applied to prepare β -amino acid derivative as a key intermediate for the synthesis of a novel carbapenem 1 . Combination of the allylzinc reagents and chiral imine, which was derived from l-valine methyl ester as a chiral auxiliary afforded a homoallylamine in good yield with excellent diastereoselectivity. diastereoselective allylation - chiral imine - homoallylamine - 1- β -methylcarbapenem",10.1055/s-2001-18100,2001-01-01,0.6020988914200757
Journal of Organic Chemistry,"Total Synthesis and Structural Determination of XR774, a Tyrosine Kinase Inhibitor","Total synthesis and structural determination of XR774 has been accomplished. The benzo[ j]fluoranthene skeleton has been constructed by regioselective coupling between tetraline 3 and tetralone 4 successively followed by the sequential transformation including the Birch reduction to prepare allylic alcohol, simultaneous bromination of vinylic and aromatic moieties, and the nickel-mediated intramolecular coupling reaction. The optical resolution of racemic 17 led to the first total synthesis of (-)-XR774.",10.1021/acs.joc.7b02997,2018-01-16,0.6020950878616519
Synthesis,"Straightforward and Scalable Synthesis of Orthogonally Protected 3,7-Diazabicyclo[4.1.0]heptane","Orthogonally N-protected (Boc and Cbz) 3,4-aziridinopiperidine is a versatile building block for the synthesis of 4-substituted 3-aminopiperidines, which are compounds with a high potential for biological activity. A multigram synthesis over five steps, starting with extraordinarily simple materials (pyridine and benzyl chloride), was developed.",10.1055/s-0028-1088059,2009-04-20,0.6020949904859578
Journal of Organic Chemistry,Formal Synthesis of Cephalotaxine,"A formal synthesis of cephalotaxine, the parent member of the Cephalotaxus alkaloids, was achieved. It features a practical four-step assembly of the benzazepine-bearing pentacyclic ring system through two alkylation reactions, acidic hydrolysis, and aldolization.",10.1021/jo302608a,2012-12-05,0.6020890592726181
Journal of Organic Chemistry,Chemoenzymatic Synthesis of Isogalactofagomine,"A new chemoenzymatic synthesis of optically pure isogalactofagomine 2 starting from achiral starting materials is presented. Dimethyl 4-hydroxypyridine-3,5-dicarboxylate (7) was synthesized and converted to the corresponding saturated piperidine 8. Then the key step of the synthesis was carried out: Lipase M catalyzed hydrolysis of the prochiral diester 8 to cause formation of an asymmetric monoacid with at least 98% enantiomeric excess. Reduction of the acid, saponification of the remaining ester, and radical iododecarboxylation gave an iodide that after substitution with silver trifluoroacetate and hydrolysis gave 2.",10.1021/jo000699r,2000-10-06,0.6020870673496368
Angewandte Chemie International Edition,Total Synthesis of Metaphanine and Oxoepistephamiersine,"Abstract Herein, we report a concise and divergent synthesis of the complex hasubanan alkaloids metaphanine and oxoepistephamiersine from commercially available and inexpensive cyclohexanedione monoethylene acetal. Our synthesis features a palladium‐catalyzed cascade cyclization reaction to set the tricyclic carbon framework of the desired molecules, a regioselective Baeyer–Villiger oxidation followed by a MeNH 2 triggered skeletal reorganization cascade to construct the benzannulated aza [4.4.3]propellane, and a strategically late‐stage regio‐/diastereoselective oxidative annulation of sp 3 C−H bond to form the challenging THF ring system and hemiketal moiety in a single step. In addition, a highly enantioselective alkylation of cyclohexanedione monoethylene acetal paved the way for the asymmetric synthesis of target molecular.",10.1002/anie.202310917,2023-08-21,0.6020856414781307
Tetrahedron,"An improved synthesis of 2-oxa-7-azaspiro[3,5]nonane and analogs as novel reagents in medicinal chemistry",,10.1016/j.tetlet.2011.04.054,2011-04-30,0.6020814645700601
Journal of Organic Chemistry,A Second-Generation Total Synthesis of (+)-Discodermolide:  The Development of a Practical Route Using Solely Substrate-Based Stereocontrol,"A novel total synthesis of the complex polyketide (+)-discodermolide, a promising anticancer agent of sponge origin, has been completed in 7.8% overall yield over 24 linear steps, with 35 steps altogether. This second-generation approach was designed to rely solely on substrate control for introduction of the required stereochemistry, eliminating the use of all chiral reagents or auxiliaries. The common 1,2-anti-2,3-syn stereotriad found in each of three subunits, aldehyde 9 (C(1)-C(5)), ester 40 (C(9)-C(16)), and aldehyde 13 (C(17)-C(24)), was established via a boron-mediated aldol reaction of ethyl ketone 15 and formaldehyde, followed by hydroxyl-directed reduction to give 1,3-diol 14. Alternatively, a surrogate aldehyde 22 was employed for formaldehyde in this aldol reaction, leading to the beta-hydroxy aldehyde 20 as a common building block, corresponding to the discodermolide stereotriad. Key fragment unions were achieved by a lithium-mediated anti aldol reaction of ester 40 and aldehyde 13 under Felkin-Anh control to provide (16S,17S)-adduct 51 and a boron-mediated aldol reaction between enone 10 and aldehyde 9, exploiting unprecedented remote 1,6-stereoinduction, to give the (5S)-adduct 57.",10.1021/jo048534w,2004-12-04,0.6020799623349276
Journal of Organic Chemistry,An Alternative Focus for Route Design for the Synthesis of Antibody–Drug Conjugate Payloads,"An analysis of Antibody-Drug Conjugate Payload manufacturing has revealed that the majority of the cost is associated with the use of high-containment facilities for the latter stages of the synthesis. To make a significant reduction in the Cost of Goods (CoGs), a new approach to route design has been introduced which focuses on minimizing the number of steps that require high containment. This approach has been exemplified in a new synthesis of tesirine, including the first application of a ring-closing copper(I)/TEMPO aerobic oxidation to the pyrrolobenzodiazepine ring system, affording a 60% reduction in CoGs.",10.1021/acs.joc.8b02876,2019-01-02,0.6020715147517164
Angewandte Chemie International Edition,β‐Selective <i>C</i>‐Glycosylation and its Application in the Synthesis of Scleropentaside A,"C-Glycosides are carbohydrates that bear a C-C bond to an aglycon at the anomeric center. Due to their high stability towards chemical and enzymatic hydrolysis, these compounds are widely used as carbohydrate mimics in drug development. Herein, we report a general and exclusively β-selective method for the synthesis of a naturally abundant acyl-C-glycosidic structural motif first found in the scleropentaside natural product family. A Corey-Seebach umpolung reaction as the key step in the synthesis of scleropentaside A and analogues enables the β-selective construction of the anomeric C-C bond starting from unprotected carbohydrates in only four steps. The one-pot approach is highly atom-efficient and avoids the use of toxic heavy metals.",10.1002/anie.201900995,2019-02-15,0.602067851405593
Journal of Organic Chemistry,Synthetic Approach to the AB Ring System of Ouabain,"Several novel hydroxylated cis-decalin derivatives, potential intermediates for the synthesis of the AB ring system of the important cardiotonic steroid ouabain, have been synthesized from commercially available starting materials. The first step in the preparation of these highly functionalized intermediates is a Robinson annulation of the beta-keto ester 6 and the 4-silyl-3-buten-2-one 5 to furnish the octalone 4 with good diastereoselectivity in fair yield (due to competition with a novel silicon-to-carbon phenyl migration). Reduction of the epoxy alcohol 3 (derived from 4 in two high-yielding steps) with LiAlH(4) gave a mixture of the desired triol 11 along with the product of an unusual reductive opening at the tertiary carbon, namely the triol 12. A plausible mechanism for this unusual reduction is presented as are possible methods for avoiding it. In particular, reduction of the corrresponding epoxy ketone 15 with aluminum amalgam proceeded in good yield to give the hydroxy ketone 16. Also reduction of the epoxide ester having the inverted stereochemistry at C3 afforded the desired tertiary alcohol 33 in good yield. Another approach using the beta,gamma-unsaturated ketal 38 permitted the formation of the tertiary alcohol 40. Fleming oxidation of the related, very functionalized silane 39 afforded the desired 1beta-alcohol 41 in fair yield. Finally a novel rearrangement was observed when the epoxy alcohol 24 was treated with DIBAL to effect loss of the angular hydroxymethyl group to produce the tetrasubstitued alkene 29 in high yield.",10.1021/jo020454+,2003-03-04,0.6020673115726093
Organic Letters,"Short Synthesis of the 6,6-Spiroketal Cores of Spirofungins A and B","[reaction: see text] Initial efforts toward the total synthesis of the antifungal antibiotics spirofungins A and B are reported. A short and efficient synthesis of the C9-C20 6,6-spiroketal fragments of both compounds is described. This asymmetric approach uses a very efficient alkylation of a lithiated N,N-dimethylhydrazone followed by spiroketal formation under acidic conditions.",10.1021/ol0491078,2004-06-29,0.6020669742376544
Tetrahedron,"A new alkaloid, pandanamine; finding of an anticipated biogenetic intermediate in Pandanus amaryllifolius Roxb",,10.1016/s0040-4039(01)00339-2,2001-04-01,0.60206145931907
Tetrahedron,"A novel and convenient route for the construction of 5-((1H-1,2,4-triazol-1-yl)methyl)-1H-indoles and its application in the synthesis of Rizatriptan",,10.1016/j.tetlet.2014.05.063,2014-05-22,0.6020607490346517
Organic Letters,"Synthesis of Cladobotryal, CJ16,169, and CJ16,170","Condensation of hydroxypyridone 7 with ethyl pyruvate and p-chlorothiophenol, reduction, and cyclization afforded 77% of lactone 6. Protection of the pyridone, acylation of the enolate with tigloyl chloride, and deprotection provided keto lactone 22. Reduction and dehydrative cyclization completed short and efficient syntheses of 2 and 3.",10.1021/ol049130t,2004-07-20,0.6020597108314472
Angewandte Chemie International Edition,"Divergent Total Synthesis of Indoxamycins A, C, and F","The concise and divergent total synthesis of (−)-indoxamycins A, C, and F has been completed for the first time by using a tricyclic enone as the common late-stage intermediate. The key steps of the strategy are based on an Ireland–Claisen rearrangement, a stereodivergent reductive 1,6-enyne cyclization, and a tandem 1,2-addition/oxa-Michael/methylenation reaction.",10.1002/anie.201307426,2013-10-31,0.6020574918574783
Angewandte Chemie International Edition,Total Synthesis and Absolute Configuration of the Guaiane Sesquiterpene Englerin A,"Catnip craze: Nepetalactone, the psychoactive ingredient of catmint, was selected as starting material for the first enantioselective synthesis of englerin A. This cytotoxic guaiane sesquiterpene is a highly selective inhibitor (1–87 nM) of several renal cancer cell lines. The absolute configuration of this natural product was determined by total synthesis.",10.1002/anie.200905032,2009-10-30,0.6020526767083066
Organic Letters,Synthesis of the Bis-tetrahydropyran Core of Amphidinol 3,A convergent synthesis of the C31-C52 bis-tetrahydropyran core of the natural product amphidinol 3 is reported. A common intermediate was synthesized from d-tartaric acid utilizing an asymmetric glycolate alkylation/ring-closing metathesis sequence to construct the THP rings. Differential elaboration of the common intermediate allowed the synthesis of two distinct coupling partners which were joined through a modified Horner-Wadsworth-Emmons olefination to provide the bis-tetrahydropyran core.,10.1021/ol1015898,2010-08-12,0.6020524473072029
Synlett,Stereoselective or Exclusive Synthesis of Ethyl (Z)-2-(2-Substituted-thiazol-4-yl)pent-2-enoates from Ethyl (E/Z)-2-(2-Bromoacetyl)pent-2-enoate,"A stereoselective or exclusive approach to a series of ethyl ( Z )-2-(2-substituted-thiazol-4-yl)pent-2-enoates from ethyl ( E / Z )-2-(2-bromoacetyl)pent-2-enoate and thioureas or thioamides was reported in good yields. This approach involves a quaternary carbon stereocontrolled cis -configuration formation, and opportunely blocking a potential E / Z isomerization. The practical applicability was highlighted by the synthesis of ( Z )-2-(2- tert -butoxycarbonylaminothiazol-4-yl)pent-2-enoic acid, a commercially important side-chain material of cefcapene pivoxil, in a two-step procedure.",10.1055/s-0033-1338954,2013-06-05,0.602049620801194
Journal of the American Chemical Society,Total Synthesis of (+)-Mycotrienol and (+)-Mycotrienin I:  Application of Asymmetric Crotylsilane Bond Constructions,"A highly convergent asymmetric synthesis of the ansamycin antibiotics (+)-mycotrienin I ( 1c ) and (+)-mycotrienol ( 1d ) has been achieved through the synthesis and coupling of the C9−C16 subunit 3b and the aromatic subunit 4b, respectively. This article describes the complete details of that work as it illustrates the utility of our developing chiral ( E )-crotylsilane bond construction methodology in total synthesis. All four stereogenic centers were introduced using chiral allylsilane bond construction methodology. In the synthesis of subunit 3b, the C12 and C13 stereocenters were installed using an asymmetric crotylsilylation reaction to α-keto dibenzyl acetal 5 . The C11 stereocenter was subsequently installed via a chelate-controlled addition of allyltrimethylsilane to establish the anti -1,3-diol system. The C14−C15 trisubstituted double bond was then installed via a reductive opening of α,β-unsaturated lactone 10b . Aromatic subunit 4b was chosen on the basis of its synthon equivalency to the amidobenzoquinone system of (+)- 1c and (+)- 1d . Subunit 4b was constructed in a concise six-step sequence which incorporates the C3 stereogenic center of the C1−C5 side chain. The C3 stereogenic center was established using a Weinreb amidation of aniline 18 with lactone (+)- 16, whose absolute stereochemistry was derived using the crotylsilane methodology. The union of subunit 3b with aromatic subunit 4b was accomplished using a sulfone-based coupling strategy. Coupling product 21 was transformed through a sequence of steps to triene 24 . Divergence from this advanced intermediate allows access to both natural products. The successful completion of the synthesis included the incorporation of the ( E,E,E )-triene unit with simultaneous macrocyclization through a palladium (0)-catalyzed (Stille-type) coupling macrocyclization.",10.1021/ja9743194,1998-04-17,0.6020467332996836
European Journal of Organic Chemistry,Pactamycin and Its Derivatives: Improved Synthesis Route,"Stereoselective construction of the cyclopentane core 21 of pactamycin ( 1 ) was achieved from symmetric cyclohexadiene 7 . Our synthetic strategy features catalytic Rh‐mediated desymmetric aziridination of the cyclohexadiene derivative, selective ring‐opening reaction at the C2 position of sulfonylaziridine with NaN 3 , ring‐contraction of cyclohexene 9 by ozonolysis followed by intramolecular aldol reaction via enamine intermediate 11 , and construction of the two consecutive tetra‐substituted carbon centers by stereoselective epoxidation of the exo ‐methylene moiety of 14c with DMDO, followed by methylation reaction. Introduction of the urea unit on tetra‐substituted carbon of 16 was achieved by amidation and subsequent Hofmann rearrangement.",10.1002/ejoc.201901747,2019-12-12,0.6020453293177623
Journal of the American Chemical Society,Enantioselective Total Syntheses of Manzamine A and Related Alkaloids,"As a prelude to undertaking the total syntheses of the complex manzamine alkaloids, a series of model studies were conducted to establish the scope and limitations of intramolecular [4 + 2] cycloadditions of N-acylated vinylogous ureas with the trienic substrates 17a,b, 28a,b, and 34. These experiments clearly demonstrated that the geometry of the internal double bond and the presence of an electron-withdrawing group on the diene moiety were essential for the facile and stereoselective formation of the desired cycloadducts. The enantioselective syntheses of the manzamine alkaloids ircinol A (75), ircinal A (5), and manzamine A (1) were then completed by employing a convergent strategy that featured a novel domino Stille/Diels-Alder reaction to construct the tricyclic ABC ring core embodied in these alkaloids. Thus, the readily accessible chiral dihydropyrrole 58 was first converted in a single chemical operation into the key tricyclic intermediate 60. Two ring-closing metathesis reactions were then used to form the 13- and 8-membered rings leading to Z-72 and 74, the latter of which was quickly elaborated into ircinal A (5) via ircinol A (75). The synthetic 5 thus obtained was converted into manzamine A (1) following literature precedent. This concise synthesis of ircinal A required a total of 24 operations from commercially available starting materials with the longest linear sequence being 21 steps.",10.1021/ja0202964,2002-06-22,0.6020449094743585
Angewandte Chemie International Edition,Enantioselective Total Synthesis of Cymoside through a Bioinspired Oxidative Cyclization of a Strictosidine Derivative,"The first total synthesis of the caged monoterpene indole alkaloid cymoside is reported. This natural product displays a unique hexacyclic-fused skeleton whose biosynthesis implies an early oxidative cyclization of strictosidine. Our approach to the furo[3,2-b]indoline framework relied on an unprecedented biomimetic sequence which started by the diastereoselective oxidation of the indole ring into a hydroxyindolenine which triggered the addition of an enol ether and was followed by the trapping of an oxocarbenium intermediate.",10.1002/anie.201912812,2019-12-04,0.6020433045983208
Tetrahedron,"Monamycin synthetic studies. Pt 1. An enantiospecific total synthesis of (3S,5S)-5-hydroxypiperazic acid from D-mannitol",,10.1016/s0040-4039(98)01533-0,1998-09-01,0.6020379657319496
Journal of Organic Chemistry,Synthesis of Iduronic Acid Building Blocks for the Modular Assembly of Glycosaminoglycans,"The modular synthesis of glycosaminoglycans requires straightforward methods for the production of large quantities of protected uronic acid building blocks. In particular, the preparation of fully differentiated iduronic acids has proven particularly challenging. An efficient route to methyl 3-O-benzyl-1,2-O-isopropylidene-alpha-l-idopyranosiduronate 6 from diacetone glucose in nine steps and 36% overall yield is described. Idopyranosiduronate 6 is useful as a glycosyl acceptor and as an intermediate that may be further elaborated into iduronic acid trichloroacetimidate glycosyl donors for the assembly of glycosaminoglycan structures as illustrated here.",10.1021/jo0340760,2003-08-28,0.6020332755562764
Synthesis,A General Synthesis of 1-Nitro-2-phenyl-4-oxospiro[2.5]octanes,All articles of this category The novel title compounds 6 and 7 were conveniently synthesized by a facile two-step route starting from (2-chloro-2-nitroethenyl)benzenes 2 via the base-induced cyclopropanations of the intermediate 2-(2-chloro-2-nitro-1-phenylethyl)cyclohexanones 3 and 4 .,10.1055/s-1992-26098,1992-01-01,0.6020324894034947
Tetrahedron,"Synthesis of amylostatin (XG), α-glucosidase inhibitor with basic pseudotrisaccharide structure",,10.1016/s0040-4039(00)85830-x,1982-01-01,0.6020322712995131
Journal of the American Chemical Society,Total synthesis of 9-dihydroerythronolide B derivatives and of erythronolide B,"A convergent total synthesis (22 steps on the longest linear route) of (-)-erythronolide B (5) and two 9-dihydro derivatives (52 and 54) thereof from (R)-2,3-O-isopropylideneglyceraldehyde (20) as the only source of chirality is described. A key step of the synthesis is the regio- and stereocontrolled coupling of the allyl sulfide anion 39 and ketone 26, which can be directed to either alpha-adduct 40 or 41 by an appropriate choice of the conditions (Scheme V, Table II). From 40 and 41 the seco acids 47 and 49 are prepared, which are smoothly macrolactonized to 50 and 51 according to a modified Yamaguchi procedure. Hydroboration of 50 and 51 proceeds under macrocyclic stereocontrol to afford the 9-dihydroerythronolide B derivatives 52 and 54, of which 54 is converted into 5 by a known oxidation-deketalizaton sequence.",10.1021/ja00003a026,1991-01-01,0.6020288575647359
Organic Letters,Silyllithium-Initiated Coupling of α-Ketoamides with <i>tert</i>-Butanesulfinylimines for Stereoselective Synthesis of Enantioenriched α-(Silyloxy)-β-amino Amides,"A silyllithium-initiated coupling of α-ketoamides with tert-butanesulfinylimines was developed for the efficient, stereoselective synthesis of enantioenriched α-(silyloxy)-β-amino amides. Nucleophilic addition of silyllithium to α-ketoamides, followed by 1,2-Brook rearrangement, generates nucleophilic enolates, which are then intercepted by chiral imines to provide three-component coupling products. Use of α-ketoamides is critical for achieving high yields and diastereoselectivities in the resulting α-hydroxy-β-amino acid derivatives.",10.1021/acs.orglett.6b00006,2016-01-26,0.6020287959897982
Synlett,"Ethoxycarbonylmethylenetriphenylphosphorane in Carbohydrate Chemistry, Part III:§ A Short and Highly Efficient Synthesis of (-)-Epigoniofufurone","All articles of this category (-)-Epigoniofufurone is synthesised in a very efficient way from diacetone glucose in 6 steps in 30% overall yield. The highlight of our synthesis is a fortuitous one-pot elaboration of 2-deoxy-3,6-anhydro-1,4-glyconolactone skeleton present in the natural product by a bis-cyclisation process accompanying the Wittig reaction of 2-hydroxy free lactol with the title ylide.",10.1055/s-1993-22371,1993-01-01,0.6020240013489776
European Journal of Organic Chemistry,"Expedient Approach to α,β‐Unsaturated δ‐Lactones through a Catalytic Asymmetric [2+2] Cycloaddition","The stereoselective synthesis of the cis ‐γ,δ‐disubstituted α,β‐unsaturated δ‐lactone fragment of the leustroducsins or phoslactomycins was accomplished. The new synthetic strategy involves a catalytic asymmetric ketene–aldehyde [2+2] cycloaddition leading to the formation of a cis ‐disubstituted β‐lactone. Ring extension by enolate condensation and subsequent recyclisation then gave the target δ‐lactone in a straightforward fashion. Coupling studies with cyclohexanone are also reported.",10.1002/ejoc.201701336,2017-10-19,0.6020239157160068
Journal of Organic Chemistry,Ru-Catalyzed Asymmetric Hydrogenation of Chiral δ-Hydroxy-β-Keto Acid Derivatives,"Ru-catalyzed stereoselective asymmetric hydrogenation of multifunctionalized ketones has been a formidable challenge, and few related successful works have been reported. Herein, we report our research on Ru-catalyzed asymmetric hydrogenation of chiral δ-hydroxy-β-keto acid derivatives, which achieves excellent diastereoselectivity (up to >99% de ). This procedure provides a new route for the synthesis of pure syn - and anti -3,5-dihydroxy acid derivatives, which serve as key intermediates in natural products and drug molecules, such as statins.",10.1021/acs.joc.4c02766,2025-05-17,0.6020210054201128
Tetrahedron,A mild and efficient method for the formation of a key intermediate in penem chemistry,,10.1016/0040-4039(95)00765-5,1995-06-01,0.6020187522158824
European Journal of Organic Chemistry,Efficient Synthesis of New <i>C</i>‐Functionalized Macrocyclic Polyamines,"Abstract A powerful synthetic route for the preparation of new polyazamacrocycles, valuable precursors of bifunctional chelating agents with applications in nuclear medicine, is reported. The desired functional group was introduced onto the macrocycle backbone during the cyclization step, thus avoiding the tedious preparation of a C ‐functionalized synthon. The regioselective reaction of macrocycles bearing an aminomethyl pendant arm with aldehydes is also described.",10.1002/ejoc.200901183,2010-02-16,0.60201757946605
Journal of the American Chemical Society,Catalytic Asymmetric Syntheses of Antifungal Sphingofungins and Their Biological Activity as Potent Inhibitors of Serine Palmitoyltransferase (SPT),"Unambiguous synthetic routes to sphingofungins B and F and to their stereoisomers have been developed based on the tin(II)-catalyzed asymmetric aldol reaction (Chiral Lewis Acid-Controlled Synthesis (CLAC Synthesis)). Efficient enantioselective synthesis using a catalytic amount of a chiral source as well as the effectiveness of this strategy for the synthesis of the sphingofungin family have been successfully demonstrated. Using the stereoisomers of sphingofungin B synthesized, the relevance of its stereochemistry to its SPT inhibitory activity has been revealed.",10.1021/ja9730829,1998-01-27,0.6020151744980757
Organic Letters,Stereospecific Synthesis of the Saccharosamine-Rhamnose-Fucose Fragment Present in Saccharomicin B,A synthetic route has been developed for constructing the d -saccharosamine- l -rhamnose- d -fucose (Sac-Rha-Fuc) trisaccharide fragment present in the antibacterial natural product saccharomicin B. The Sac monosaccharide was synthesized through a modified nine step procedure starting from d -rhamnal in 23% overall yield. 1- O -TBS Sac donors were used to construct the β-linked Sac-Rha disaccharide. This disaccharide was coupled to a Fuc acceptor under BSP/Tf 2 O conditions to afford a trisaccharide properly functionalized for elaboration to saccharomicin B.,10.1021/acs.orglett.8b02028,2018-07-17,0.6019983493280855
Synlett,"Concise Syntheses of Novel Styryl Lactones, (+)-Goniofufurone, (+)-Goniopypyrone, (+)-Goniotriol, (+)-8-Acetylgoniotriol, and (+)-Altholactone","All articles of this category Enantio- and stereo-selective syntheses of goniofufurone 1 , goniopypyrone 2 , goniotriol 3 , 8-acetylgoniotriol 4 , and altholactone 5 have been accomplished from the lactonic aldehyde 6 as a key intermediate.",10.1055/s-1993-22559,1993-01-01,0.6019973043880036
Tetrahedron,Synthetic approach towards nakadomarin A: efficient synthesis of the central tetracyclic core,,10.1016/s0040-4039(01)01792-0,2001-11-01,0.6019936653625988
Tetrahedron,"New approach to the synthesis of tetrazole-containing buta-1,3-diynes: The total synthesis of 1,4-bis(2-(tert-butyl)-2H-tetrazol-5-yl)buta-1,3-diyne",,10.1016/j.tetlet.2019.151217,2019-09-27,0.6019781148428117
Synlett,"The Application of Mitsunobu Cyclization for the Synthesis of 2′,3′-Dideoxy-C-Nucleosides Designed as Didanosine Analogues","The synthesis of new 2′,3′-dideoxy-C-nucleosides structurally related to didanosine has been achieved. Their preparation involved condensation of a suitably substituted, lithiated 2- or 4-picoline with 2′,3′-dideoxy-5′-benzylribonolactone, followed by borohydride reduction of the resulting hemiacetals, intramolecular Mitsunobu cyclization of the derived diols, formation of the pyrazolo[3,4-c] or [4,3-b]pyridine ring-system and subsequent removal of the protecting groups.",10.1055/s-0029-1217364,2009-06-12,0.6019747011471633
Angewandte Chemie International Edition,Interplay of Cascade Oxidative Cyclization and Hydride Shifts in the Synthesis of the ABC Spiroketal Ring System of Pectenotoxin‐4,Concepts: The formation of stereochemically defined bis-THF units through a double cyclization and a hydride-shift-initiated route to spiroketals is described (see scheme; Xc=chiral auxiliary). The resulting sequence has been used in a synthesis of the C1-16 fragment of the naturally occurring antitumor agent pectenotoxin-4.,10.1002/anie.201208919,2013-01-30,0.6019679510690377
Angewandte Chemie International Edition,"Concise Synthesis of the Antiplasmodial Isocyanoterpene 7,20‐Diisocyanoadociane","The flagship member of the antiplasmodial isocyanoterpenes, 7,20-diisocyanoadociane (DICA), was synthesized from dehydrocryptone in 10 steps, and in 13 steps from commercially available material. Our previous formal synthesis was reengineered, leveraging only productive transformations to deliver DICA in fewer than half the number of steps of our original effort. Important contributions, in addition to the particularly concise strategy, include a solution to the problem of axial nucleophilic methylation of a late-stage cyclohexanone, and the first selective synthesis and antiplasmodial evaluation of the DICA stereoisomer with both isonitriles equatorial.",10.1002/anie.201906834,2019-07-04,0.6019679208583224
Synlett,Synthetic Efforts Towardsthe Synthesis of the Complex Diterpene Providencin,"Providencin is a novel, highly oxygenated marine furanocembranolide featuring a cyclobutane ring and a highly strained 7,8-trans-epoxide. Various approaches to the total synthesis of this compound are reported. The cyclobutane moiety is generated via [2+2] cycloaddition and the furan ring is constructed via a Wipf ­palladium-catalyzed alkynone cyclization. The macrocyclic ring is closed via a Horner-Wadsworth-Emmons olefination or ring-­closing metathesis. The latter reaction, however, produces the undesired 7,8-Z-olefin exclusively, and the conversion into the E-isomer has been, thus far, unsuccessful.",10.1055/s-0028-1216728,2009-04-17,0.6019501802822615
Journal of Organic Chemistry,"Aplyronine A, a Potent Antitumor Substance of Marine Origin, Aplyronines B and C, and Artificial Analogues:  Total Synthesis and Structure−Cytotoxicity Relationships","The enantioselective total synthesis of aplyronine A ( 1 ), a potent antitumor substance of marine origin, was achieved by a convergent approach. Three segments 4, 5, and 6, corresponding to the C5−C11, C21−C27, and C28−C34 portions of aplyronine A ( 1 ), were prepared using the Evans aldol reaction and the Sharpless epoxidation as key steps. The coupling reaction of 4 with iodide 7 followed by Julia olefination with sulfone 8 gave the C5−C20 segment 9, while the Julia coupling reaction between segments 5 and 6 provided the C21−C34 segment 10 . Julia olefination between segments 9 and 10 and the subsequent four-carbon homologation reaction led to seco acid 83, which was converted into aplyronine A ( 1 ) by Yamaguchi lactonization followed by the introduction of two amino acids. The use of the [(3,4-dimethoxybenzyl)oxy]methyl group as a protecting group for the hydroxyl at C29 was crucial for this synthesis. The enantioselective synthesis of two natural congeners, aplyronines B ( 2 ) and C ( 3 ), was also carried out using the intermediates for the synthesis of 1, which determined the absolute stereostructures of 2 and 3 unambiguously. To study the structure−cytotoxicity relationships of aplyronines, artificial analogues of 1 were synthesized and their cytotoxicities were evaluated: the trimethylserine moiety, two hydroxyl groups, and the side-chain portion in 1 turned out to be important in the potent cytotoxicity shown by 1 . Biological studies with aplyronine A ( 1 ) showed that 1 inhibited polymerization of G-actin to F-actin and depolymerized F-actin to G-actin.",10.1021/jo9606113,1996-01-01,0.6019490620073068
Journal of the American Chemical Society,Synthesis of Leucascandrolide A via a Spontaneous Macrolactolization,"We have developed a concise, convergent, and stereocontrolled synthesis of (+/-)-leucascandrolide A (18 steps from commercially available precursors), featuring a complete relay of the initial stereochemical information via a series of diastereoselective transformations. Spontaneous macrolactolization discovered during this synthetic exercise has provided unprecedented access to this macrolide and demonstrated the possibility of accessing even large-ring systems in a highly controlled and efficient manner.",10.1021/ja028428g,2002-10-24,0.6019410844104645
Organic Letters,Stereocontrolled Synthesis of (±)-Melokhanine E via an Intramolecular Formal [3 + 2] Cycloaddition,"A convergent sequence to access the indole alkaloid (±)-melokhanine E in 12-steps (8-step longest linear sequence) and an 11% overall yield is reported. The approach utilizes two cyclopropane moieties as reactive precursors to a 1,3-dipole and imine species to enable stereoselective construction of the core scaffold through a formal [3 + 2] cycloaddition. The natural product was evaluated for its antimicrobial activity based on isolation reports; however, no activity was observed. The reported efforts serve as a synthetic platform to prepare an array of alkaloids bearing this core structural motif.",10.1021/acs.orglett.9b04546,2020-01-07,0.6019209960164129
Organic Process Research & Development,New and Efficient Synthetic Approaches for the Regioisomeric and Iminium Impurities of Clopidogrel Bisulfate,New and concise synthetic routes have been devised for the regioisomeric and iminium impurities of clopidogrel bisulfate. The synthesis features utilization of commercially available starting materials and simple reactions.,10.1021/op300110m,2012-08-15,0.6019203550226012
Synthesis,"Synthesis of a Series of Novel 3,9-Disubstituted Phenanthrenes as Analogues of Known N-Methyl-d-aspartate Receptor Allosteric Modulators","9-Substituted phenanthrene-3-carboxylic acids have been reported to have allosteric modulatory activity at the NMDA receptor. This receptor is activated by the excitatory neurotransmitter L-glutamate and has been implicated in a range of neurological disorders such as schizophrenia, epilepsy and chronic pain and neurodegenerative disorders such as Alzheimer's disease. Herein, the convenient synthesis of a wide range of novel 3,9-disubstituted phenanthrene derivatives starting from a few common intermediates is described. These new phenanthrene derivatives will help to clarify the structural requirements for allosteric modulation of the NMDA receptor.",10.1055/s-0034-1380114,2015-03-19,0.6019079560120353
Angewandte Chemie International Edition,Total Synthesis of (+)‐Minfiensine: Construction of the Tetracyclic Core Structure by an Asymmetric Cascade Cyclization,"A new method for one-step construction of the tetracyclic core structure of the indole alkaloid (+)-minfiensine was developed utilizing a palladium-catalyzed asymmetric indole dearomatization/iminium cyclization cascade. An efficient total synthesis of (+)-minfiensine was realized using this strategy. The present method enables access to the common core structure of a series of monoterpene indole alkaloids, such as vincorine, echitamine, and aspidosphylline A.",10.1002/anie.201602771,2016-05-13,0.6019000805013986
Organic Letters,Application of the Rodriguez–Pattenden Photo-Ring Contraction: Total Synthesis and Configurational Reassignment of 11-Gorgiacerol and 11-Epigorgiacerol,"A stereospecific photochemical ring contraction was used as the key step in the first total synthesis of the marine pseudopteranyl diterpene 11-gorgiacerol and its 11-epimer. The synthesis allowed the correction of the configurations that had been misassigned in the literature. In addition, some novel pseudopteranyl derivatives have been made.",10.1021/ol301068h,2012-05-16,0.6018950538043
Journal of Organic Chemistry,From a Biogenetic Scenario to a Synthesis of the ABC Ring of Manzamine A,"On the basis of a biogenetic proposal for explaining the biogenesis of manzamine A, the cycloaddition of dihydropyridinium salt 26 with diene derivative 5 leads to adducts 27. These adducts, as well as their related and previously described analogues 9, are now shown to be precursors of diene derivatives such as 10, 13, and 28. Treatment of diene 32 with sodium azide resulted in a one-step formation of the tricyclic imino derivative 34. This key intermediate was further transformed into tricyclic derivative 40, which possesses the essential features of the ABC ring of manzamine A.",10.1021/jo0162033,2002-02-21,0.6018899183308436
Angewandte Chemie International Edition,Total Synthesis of (−)‐Batrachotoxin Enabled by a Pd/Ag‐Promoted Suzuki–Miyaura Coupling Reaction,"Abstract Batrachotoxin is an extremely potent cardio‐ and neurotoxic steroidal alkaloid found in certain species of frogs, birds, and beetles. The steroidal 6/6/6/5‐membered carbocycle (ABCD‐ring) is U‐shaped and functionalized with two double bonds, a six‐membered C3‐hemiacetal across the AB‐ring, a seven‐membered oxazepane on the CD‐ring, and a dimethylpyrrolecarboxy group at the D‐ring carbon chain. These structural features present an unusual and formidable synthetic challenge. Herein we report a total synthesis of batrachotoxin based on a newly devised convergent strategy through a 22‐step sequence. Enantiopure AB‐ring and D‐ring fragments were prepared and subjected to a crucial C(sp 2 )−C(sp 2 ) coupling reaction. Although both C(sp 2 ) centers were sterically encumbered by proximal tetrasubstituted carbon atoms, Ag 2 O strongly promoted the Pd(PPh 3 ) 4 ‐catalyzed Suzuki–Miyaura coupling reaction at room temperature, thereby connecting the two fragments without damaging their preexisting functionalities. Subsequent treatment with t ‐BuOK induced Dieckmann condensation to cyclize the C‐ring. The judiciously optimized functionalizations realized oxazepane formation, carbon chain extension, and pyrrole carboxylic acid condensation to deliver batrachotoxin.",10.1002/anie.202309688,2023-08-16,0.6018838994908272
Synthesis,"Modified Preparation of (2<i>R</i>)-2-<i>tert</i>-Butyl-6-methyl-4<i>H</i>-1,3-dioxin-4-one; a Chiral Acetylacetic Acid Derivative for the Synthesis of Enantiopure Compounds","All articles of this category An improved synthesis of the title compound in ca. 45% yield on up to a 174 mmol scale is reported. Bromination of (2 R ,6 R )-2- tert -butyl-6-methyl-1, 3-dioxan-4-one gives a mixture of mono- and dibromides which must be purified by chromatography to remove impurities which may poision the palladium catalyst in the following dehalogenation step.",10.1055/s-1992-34162,1992-01-01,0.601881821295001
Synthesis,"A Novel and Convenient Synthesis of ‘Reversed’ Diamidino 2,5-Aryl- and 2,5-Azaheterocycle-Substituted Furans","A novel and convenient two-step synthesis of ‘reversed’ diamidino 2,5-aryl- and 2,5-azaheterocycle-substituted furans is described. The key step, a Stille cross-coupling reaction between N-(bromoaryl)arenecarboxamidines and 2,5-bis(tri-n-butylstannyl)furan, is reported for the first time.",10.1055/s-0029-1216817,2009-05-14,0.601881734189889
Organic Letters,Nine-Step Stereoselective Synthesis of Islatravir from Deoxyribose,"A stereoselective nine-step synthesis of the potent HIV nucleoside reverse transcriptase translocation inhibitor (NRTTI) islatravir (EfdA, MK-8591) from 2-deoxyribose is described. Key findings include a diastereodivergent addition of an acetylide nucleophile to an enolizable ketone, a chemoselective ozonolysis of a terminal olefin and a biocatalytic glycosylation cascade that uses a unique strategy of byproduct precipitation to drive an otherwise-reversible transformation forward.",10.1021/acs.orglett.0c00239,2020-02-28,0.6018791967515627
Tetrahedron,"An efficient route to 2,3-disubstituted indoles via reductive alkylation using H2 as reductant",,10.1016/j.tetlet.2011.03.099,2011-04-15,0.6018738538715652
European Journal of Organic Chemistry,Synthesis of Spirocyclopropanated Analogues of Imidacloprid and Thiacloprid,"Abstract tert ‐Butyl N ‐[1‐(hydroxymethyl)cyclopropyl]carbamate ( 8 ) was converted into spirocyclopropanated analogues 14 ‐CP and 14 ‐CT of the insecticide Thiacloprid ( 2 ) in six simple steps with overall yields of 24 % each, along with their regioisomers 13 ‐CP and 13 ‐CT in overall yields of 17 and 15 %, respectively. The spirocyclopropanated analogues 27 ‐CP and 27 ‐CT of the insecticide Imidacloprid ( 1 ) were prepared from 8 in five steps in an overall yield of 10 % each, along with their regioisomers 20 ‐CP and 20 ‐CT in an overall yield of 8 and 7 %, respectively. The key step in all preparations was a cocyclization of an appropiately protected (1‐aminocyclopropyl)methyl derivative with S , S ‐dimethyl cyanodithioiminocarbonate ( 11 ) or nitroguanidine ( 22 ). The structures of several final products and by‐products were verified by X‐ray crystal structure analyses.",10.1002/ejoc.200400599,2005-02-01,0.6018607600850346
Journal of the American Chemical Society,Synthesis of a Glycosylphosphatidylinositol Anchor Bearing Unsaturated Lipid Chains,"A GPI anchor bearing unsaturated fatty acid lipid chains (1) was synthesized by a highly convergent strategy employing the para-methoxybenzyl group for permanent hydroxyl protection. The final global deprotection was achieved by an efficient three-step, one-pot procedure to give an 81% isolated yield of the target structure.",10.1021/ja1009037,2010-04-27,0.6018604230211785
Tetrahedron,Preparation of lactones with several ring sizes via the same intermediate,,10.1016/s0040-4039(00)60488-4,1993-04-01,0.6018572152238288
Tetrahedron,Studies toward the total synthesis of (−)-kampanol A: an efficient construction of the ABCD ring system,,10.1016/s0040-4039(02)01859-2,2002-10-01,0.6018526196887717
Tetrahedron,Studies toward the total synthesis of eletefine: an efficient construction of the AB ring system,,10.1016/j.tetlet.2010.08.058,2010-08-23,0.6018526196887717
Organic Letters,Synthesis of Bradyrhizose from <scp>d</scp>-Glucose,"We describe the synthesis of the unusual bicyclic sugar bradyrhizose in 14 steps and a 6% overall yield from d -glucose. The synthesis involves the elaboration of a trans -fused carbocyclic ring onto the preexisting glucopyranose framework followed by adjustment of the oxidation levels. Key steps include radical extension of the glucopyranose side chain, ring closing metathesis, allylic oxidation, Luche reduction, hydroxy-directed epoxidation, and acid-catalyzed epoxide opening at the more substituted position.",10.1021/acs.orglett.9b04279,2019-12-26,0.6018512653859223
Tetrahedron,Practical and efficient synthesis of N-halo compounds,,10.1016/j.tetlet.2004.12.088,2005-01-14,0.6018453094510363
Organic Letters,"Desymmetrization of 2,4,5,6-Tetra-<i>O</i>-benzyl-<scp>d</scp>-<i>myo</i>-inositol for the Synthesis of Mycothiol","An efficient chemical synthesis of mycothiol involving the regioselective ketopinyl desymmetrization of 2,4,5,6-tetrabenzylated D-myo-inositol as the key step is described. Together with a highly α-stereoselective D-glucosaminylation, the whole procedure was accomplished in eight steps with an overall yield of 40%.",10.1021/ol202218n,2011-09-15,0.6018427583694027
Journal of Organic Chemistry,Total Synthesis of (+)-Yohimbine via an Enantioselective Organocatalytic Pictet–Spengler Reaction,"The binolphosphoric acid-catalyzed Pictet-Spengler reaction of an N-(5-oxy-2,4-pentadienyl)tryptamine derivative with methyl 5-oxo-2-(phenylseleno)pentanoate leads to the tetrahydro-β-carboline in a 92:8 enantiomeric ratio. This product is easily converted into the substrate for a stereoselective intramolecular Diels-Alder reaction of the type earlier reported by Jacobsen. These two key steps constitute the basis for a nine-step total synthesis of (+)-yohimbine from tryptamine. A similar asymmetric Pictet-Spengler reaction was applied to the synthesis of an intermediate in the recent total synthesis of corynantheidine by Sato.",10.1021/jo201657n,2011-09-27,0.6018268550685635
Angewandte Chemie International Edition,Asymmetric Total Synthesis of Sarpagine and Koumine Alkaloids,"Abstract We report here a concise, collective, and asymmetric total synthesis of sarpagine alkaloids and biogenetically related koumine alkaloids, which structurally feature a rigid cage scaffold, with L ‐tryptophan as the starting material. Two key bridged skeleton‐forming reactions, namely tandem sequential oxidative cyclopropanol ring‐opening cyclization and ketone α‐allenylation, ensure concurrent assembly of the caged sarpagine scaffold and installation of requisite derivative handles. With a common caged intermediate as the branch point, by taking advantage of ketone and allene groups therein, total synthesis of five sarpagine alkaloids (affinisine, normacusine B, trinervine, N a ‐methyl‐16‐epipericyclivine, and vellosimine) with various substituents and three koumine alkaloids (koumine, koumimine, and N ‐demethylkoumine) with more complex cage scaffolds has been accomplished.",10.1002/anie.202102416,2021-03-30,0.6018230855219063
Journal of the American Chemical Society,Asymmetric Total Synthesis of (−)-Laulimalide:  Exploiting the Asymmetric Glycolate Alkylation Reaction,"A concise total synthesis of the potent antitumor macrolide (-)-laulimalide is described. The observation that homoallylic (or latent homoallylic) C-O bonds are present at C5, C9, C15, C19, and C23 led to the strategic decision to rely heavily on the asymmetric glycolate alkylation to construct both the C1-C14 fragment 3 and the C15-C27 subunit 4. A diastereoselective addition of a C1-C14 allylstannane to a C15-C27 alpha,beta-epoxyaldehyde served to join the two advanced fragments. A Mitsunobu macrolactonization of hydroxy acid 2 avoided isomerization of the sensitive 2,3-Z-enoate, which has been observed in base-catalyzed macrolactonizations. Removal of two TBS protecting groups to reveal the C15 and C20 hydroxyls occurred without rearrangement to isolaulimalide.",10.1021/ja026269v,2002-05-01,0.6018202791095995
Organic Letters,3-Benzyl-3-azabicyclo[3.1.1]heptan-6-one: A Promising Building Block for Medicinal Chemistry,An efficient two-step multigram synthesis of the previously unknown 3-benzyl-3-azabicyclo[3.1.1]heptan-6-one is described. The compound is shown to be a promising building block for further selective derivatization of the cyclobutane ring providing novel conformationally restricted piperidine derivatives.,10.1021/ol101866x,2010-08-26,0.6018169261153854
Organic Letters,3-Benzyl-3-azabicyclo[3.1.1]heptan-6-one: A Promising Building Block for Medicinal Chemistry,An efficient two-step multigram synthesis of the previously unknown 3-benzyl-3-azabicyclo[3.1.1]heptan-6-one is described. The compound is shown to be a promising building block for further selective derivatization of the cyclobutane ring providing novel conformationally restricted piperidine derivatives.,10.1021/ol3004707,2012-03-05,0.6018169261153854
Synthesis,Stereoseletive Total Synthesis of 11-α- and 11-β-Methoxycurvularins,"Total synthesis of 11-α-methoxycurvularin and 11-β-methoxycurvularin has been accomplished in a highly stereoselective manner by utilizing Jacobsen hydrolytic kinetic resolution, Maruoka asymmetric allylation and intramolecular Friedel-Crafts acylation as key steps.",10.1055/s-0029-1218621,2010-01-08,0.6018109970769489
Journal of the American Chemical Society,Extension of Pd-Mediated One-Pot Ketone Synthesis to Macrocyclization: Application to a New Convergent Synthesis of Eribulin,"Recently reported Pd-mediated one-pot ketone synthesis from an unactivated alkyl bromide and a thioester has been extended to a macrocyclic ketone synthesis. In situ generation of alkylzinc halide via single electron transfer (SET), using NbCpCl 4 and CrCl 3, was the key for the success of macrocyclization. A new convergent synthesis of eribulin has been achieved, using (1) catalytic asymmetric Ni/Cr-mediated coupling to form the C19–C20 bond, (2) base-induced cyclization to form the methylenetetrahydrofuran ring, and (3) Pd-mediated one-pot ketone synthesis to form the macrocyclic ketone.",10.1021/jacs.6b11663,2016-12-08,0.6018084624934981
Tetrahedron,Synthetic studies on concanamycin A: Synthesis of the C5∼C13 and C20∼C28 segments,,10.1016/s0040-4039(98)01233-7,1998-08-01,0.6018056318924075
Tetrahedron,Synthetic studies of the nargenicins: synthesis of the oxa-bridged octalin nucleus,,10.1016/s0040-4039(01)81305-8,1984-01-01,0.6018056318924075
Tetrahedron,Synthetic studies on vancomycin: Synthesis of seco-aglucovancomycins,,10.1016/0040-4039(95)01857-e,1995-11-01,0.6018056318924075
Tetrahedron,"Synthetic studies towards paspalicine, Part 2 : synthesis of the eastern half",,10.1016/s0040-4039(00)79673-0,1991-03-01,0.6018056318924075
Tetrahedron,"Synthetic studies on reidispongiolide A, an actin-depolymerizing marine macrolide: synthesis of C11–C22 and C23–C35 segments",,10.1016/j.tetlet.2009.06.075,2009-06-19,0.6018056318924075
Synlett,"Synthetic Studies towards (-)-Lemonomycin, Synthesis of Fused Tetracycles",International audience,10.1055/s-2006-944225,2006-07-01,0.6018056318924075
Tetrahedron,Synthetic studies on amphidinolides C and F: synthesis of the C18–C29 segment of amphidinolide F,,10.1016/j.tetlet.2009.02.093,2009-02-16,0.6018056318924075
Tetrahedron,Synthetic studies on altohyrtins (spongistatins): Synthesis of the C1C14 (AB) spiroacetal portion,,10.1016/s0040-4039(98)00619-4,1998-05-01,0.6018056318924075
Tetrahedron,Synthetic studies on altohyrtins (spongistatins): synthesis of the C29–C44 (EF) portion,,10.1016/s0040-4039(01)01069-3,2001-08-01,0.6018056318924075
Tetrahedron,"Steroids CCCXXXVI. Synthetic studies on insect hormones, part VI. The synthesis of ponasterone A and its stereochemical identity with crustecdysone",,10.1016/s0040-4039(01)98902-6,1968-01-01,0.6018056318924075
Tetrahedron,Synthetic studies of dendrobine I synthesis of the skeleton of dendrobine,,10.1016/s0040-4039(00)99728-4,1970-01-01,0.6018056318924075
Tetrahedron,Synthetic studies in steroidal alkaloids and sapogenins. VII synthesis of solanidine,,10.1016/s0040-4039(01)98998-1,1968-01-01,0.6018056318924075
Tetrahedron,Synthetic studies on FR 900482. Synthesis of a photo-triggered pro-mitosene,,10.1016/s0040-4039(97)00865-4,1997-06-01,0.6018056318924075
Tetrahedron,Synthetic studies on altohyrtins (spongistatins): synthesis of the C15–C28 (CD) spiroacetal portion,,10.1016/s0040-4039(00)00237-9,2000-04-01,0.6018056318924075
Tetrahedron,Synthetic Studies Towards Halichondrins: Synthesis of the Left Half of Halichondrins,,10.1016/s0040-4039(00)91672-1,1992-03-01,0.6018056318924075
Tetrahedron,Synthetic studies on jadomycins: synthesis of dimethyljadomycin A,,10.1016/j.tetlet.2010.01.014,2010-01-12,0.6018056318924075
Tetrahedron,Synthetic Studies Towards Halichondrins: Synthesis of the Left Halves of Norhalichondrins and Homohalichondrins,,10.1016/s0040-4039(00)91673-3,1992-03-01,0.6018056318924075
Tetrahedron,Synthetic studies toward verrucosidin: Synthesis of (±)verrucosal,,10.1016/s0040-4039(00)84999-0,1986-01-01,0.6018056318924075
Tetrahedron,Studies in synthetic photochemistry-I synthesis of naphthaphenanthridine alkaloids,,10.1016/s0040-4039(01)92230-0,1974-01-01,0.6018056318924075
Tetrahedron,Synthetic studies on basidifferquinones: the first synthesis of (±)-basidifferquinone C,,10.1016/j.tetlet.2008.02.011,2008-02-09,0.6018056318924075
Journal of the American Chemical Society,A Concise Asymmetric Total Synthesis of Aspidophytine,An expedient asymmetric total synthesis of aspidophytine is reported. A highly convergent strategy involving the sequential annulation of vinyl iodide 5 with indole 6 exploits varying modes of indole reactivity to provide aspidophytine in 23% over six steps from 5.,10.1021/ja806176w,2008-10-15,0.6017986960971413
Journal of Organic Chemistry,Total Synthesis of Neodolastane Diterpenes Trichoaurantianolides C and D,The first total synthesis of trichoaurantianolides C and D is described. An enantiocontrolled pathway leads to rapid construction of the tricyclic carbon skeleton and establishes the trans-dimethyl geometry of the quaternary bridgehead carbons via a reductive cyclization. Application of the π-allyl Stille cross-coupling leads to a nonracemic allylic alcohol as a prerequisite for the introduction of asymmetry in the cycloheptane system. Two strategies have been examined for elaboration of the unsaturated tetrahydrofuranyl ring from a common tricyclic intermediate. These efforts reveal a number of unanticipated issues of reactivity and significant stereochemical requirements for a novel acyloin rearrangement as well as the elimination and cyclodehydration of chiral α-hydroxy ketones. Key reactions leading to completion of the synthesis include the stereoselective addition of isopropenyllithium TMEDA complex and a facile chemoselective oxidation with selenium dioxide.,10.1021/acs.joc.5b00355,2015-05-14,0.6017979137171043
Organic Letters,A Short and Efficient Stereoselective Synthesis of the Polyhydroxylated Macrolactone (<i>+</i>)-Aspicilin,"[structures: see text] A short and efficient synthesis of the polyhydroxylated macrolactone (+)-aspicilin 1 using a stereoselective lithium perchlorate mediated addition of allyltributyltin to the equatorially disposed carboxaldehyde of 3 (derived from (R',R',R,S) butane diacetal protected butane tetrol 2) as the key step is described. Terminal group manipulation and Masamune-Roush olefination using phosphonate ester 4 followed by macrocyclization via ring closing metathesis afforded the natural product after partial hydrogenation and global deprotection.",10.1021/ol991214s,2000-01-01,0.6017927769413057
Synlett,Synthesis of a C20-Deoxygenated Spirangien Derivative for Target Identification,"The synthesis of a C20-deoxygenated spirangien derivative is described that allows the incorporation of various affinity labels for target identification of this potent natural product. The synthesis takes advantage of two major building blocks that can be accessed in 8 and 14 steps, respectively. The endgame joins both fragments through a selective aldol reaction and final protecting group manipulations furnish the target molecule.",10.1055/s-0034-1379980,2015-02-03,0.6017836337146196
Tetrahedron,A novel route to synthesize libraries of quinoxalines via Petasis methodology in two synthetic operations,,10.1016/j.tetlet.2011.06.115,2011-07-23,0.6017780078020094
Synlett,Synthesis of Phenol Abietane Diterpenes Based on the Oxidative Radical Cyclization Utilizing the Mn(OAc)<sub>3</sub>/Ac<sub>2</sub>O System,"A new route to phenol abietane diterpenes from trans-communic acid is reported. The key step is the transformation of a β-ketoester into the corresponding O-acetylsalicilate, via a manganese(III)-based oxidative free-radical cyclization carried out in Ac2O. Utilizing this, the first synthesis of (-)-sugikurojin A has been achieved. The immunosuppressor 19-hydroxyferruginol has also been synthesized.",10.1055/s-2007-985586,2007-09-01,0.6017694995377643
Organic Process Research & Development,Diastereoselective Reduction of the Enone Intermediate of Travoprost,"A scalable process for the diastereoselective reduction of the prochiral enone intermediate 1 has been developed with DEANB/( R )-methyl CBS as reducing agent, to obtain the key intermediate alcohol 15 R -isomer 2, used in a process for the manufacture of Travoprost ( 3 ). Various advantages of this process against the DMSB reduction assisted by ( R )-methyl CBS have been studied. Specific comparison has been made to highlight the salient features of the chosen process on yield and optical purity with those of the DMSB reduction.",10.1021/op200154p,2011-08-15,0.601769147305257
Tetrahedron,"An improved and efficient synthesis of 2-substituted 1,4-dihydropyridine derivatives via regiospecific bromination",,10.1016/s0040-4039(00)88453-1,1988-01-01,0.6017636842497331
Tetrahedron,Synthetic studies toward Swinhoeisterol A: Synthesis of the 6/6/5/7 tetracyclic core,,10.1016/j.tetlet.2023.154840,2023-11-23,0.6017597035019476
Synlett,A Regioselective Total Synthesis of the Fungal Sesquiterpene (±)-Lagopodin A,"A highly regiocontrolled total synthesis of fungal ­sesquiterpene lagopodin A, employing a combination of Claisen ­rearrangement-intramolecular diazoketone cyclopropanation and a highly regioselective cyclopropane ring cleavage, is described.",10.1055/s-2007-967971,2007-02-21,0.6017596726019527
Journal of the American Chemical Society,Evolution of a Gram-Scale Synthesis of (+)-Discodermolide,"An efficient, highly convergent, stereocontrolled total synthesis of the potent antimitotic agent (+)-discodermolide ( 1 ) has been achieved on gram scale. Key elements of the successful strategy include (1) elaboration of three advanced fragments from a common precursor ( CP ) which embodies the repeating stereochemical triad of the discodermolide backbone, (2) σ-bond installation of the Z trisubstituted olefin, exploiting a modified Negishi cross-coupling reaction, (3) synthesis of a late-stage phosphonium salt utilizing high pressure, and (4) Wittig installation of the Z disubstituted olefin and the terminal ( Z )-diene.",10.1021/ja0015287,2000-08-26,0.6017527521139064
Synthesis,The Synthesis of Pentafluorobenzoic Acid and a New Purification of Chloropentafluorobenzene,,10.1055/s-1978-24683,1978-01-01,0.6017509950861119
European Journal of Organic Chemistry,"Concise Total Syntheses of Pyrido[4,3‐<i>b</i>]carbazole Alkaloids Using Copper‐Mediated 6π‐Electrocyclization","Abstract Concise syntheses of 9‐methoxyellipticine, 3,4‐dihydroellipticine (µ‐alkaloid D), 1,2,3,4‐tetrahydroellipticine, 2‐methyl‐1,2,3,4‐tetrahydroellipticine, olivacine, 3,4‐dihydroolivacine, (±)‐guatambuine, and (±)‐janetine were developed starting from hexatriene intermediates readily obtained by Pd‐catalyzed tandem cyclization/cross‐coupling reaction of indolylborates. The route enables the facile construction of pyrido[4,3‐ b ]carbazoles by Cu‐catalyzed 6π‐electrocyclization and subsequent transformation of the pyridocarbazole intermediates into pyrido[4,3‐ b ]carbazole alkaloids.",10.1002/ejoc.201600246,2016-04-13,0.601748202313918
Synlett,"The First Asymmetric Synthesis of 1,4-Dideoxy-1,4-imino-<scp>d</scp>-talitol","The first stereoselective synthesis of 1,4-dideoxy-1,4imino-D-Talitol has been achieved in 24% overall yield from conveniently protected (S)-glyceraldimine (1), which is easily prepared from inexpensive D-mannitol. The synthesis is based on the addition of vinylmagnesium bromide to this N-benzylimine followed by Nacylation, ring-closing metathesis and asymmetric dihydroxylation. In this synthesis as many as three stereogenic centres are constructed with total stereoselectivity.",10.1055/s-2005-871534,2005-01-01,0.601744756960208
European Journal of Organic Chemistry,Molybdenum‐Catalyzed One‐Pot Multi‐Step Synthesis of <i>N</i>‐Polyheterocycles from Nitroarenes and Glycols,"Abstract We report the efficient, sustainable one‐pot synthesis of a wide variety of N ‐polyheterocycles, such as imidazo‐quinolines and quinoxalines, and furoquinolines, from easily available nitroaromatics and glycols via a molybdenum catalytic domino reduction‐imine formation‐intramolecular cyclization‐oxidation sequence. It is worth highlighting that the recycling and incorporation of the waste carbonyl byproduct, generated in the reduction step, into the final compound is realized. In addition, the overall efficiency and atom economy of the process are further improved owing to the participation of one reaction intermediate as reductant that allows lowering the amount of external reducing agent employed.",10.1002/ejoc.202400145,2024-03-16,0.6017440742152019
Tetrahedron,"Chiral pool synthesis of tetralin as AB ring segment, precursor of anthracyclines.",,10.1016/s0040-4039(00)95020-2,1985-01-01,0.6017418484075668
Journal of Organic Chemistry,"Ring Expansion-Annulation Strategy for the Synthesis of Substituted Azulenes and Oligoazulenes. 2. Synthesis of Azulenyl Halides, Sulfonates, and Azulenylmetal Compounds and Their Application in Transition-Metal-Mediated Coupling Reactions","A ""ring expansion-annulation strategy"" for the synthesis of substituted azulenes is described based on the reaction of beta'-bromo-alpha-diazo ketones with rhodium carboxylates. The key transformation involves an intramolecular Buchner reaction followed by beta-elimination of bromide, tautomerization, and in situ trapping of the resulting 1-hydroxyazulene as a carboxylate or triflate ester. Further synthetic elaboration of the azulenyl halide and sulfonate annulation products can be achieved by employing Heck, Negishi, Stille, and Suzuki coupling reactions. Reaction of the azulenyl triflate 84 with pinacolborane provides access to the azulenylboronate 91, which participates in Suzuki coupling reactions with alkenyl and aryl iodides. The application of these coupling reactions to the synthesis of biazulenes, terazulene 101, and related oligoazulenes is described, as well as the preparation of the azulenyl amino acid derivative 110.",10.1021/jo048698c,2004-11-06,0.6017344839827476
Journal of Organic Chemistry,A New Route for Installing the Isocyclic Ring on Chlorins Yielding 13<sup>1</sup>-Oxophorbines,"A new route to 13(1)-oxophorbines, the parent macrocycle of chlorophylls, begins with the synthesis of a 13-bromochlorin. Pd-mediated coupling of the latter with tributyl(1-ethoxyvinyl)tin and subsequent acidic hydrolysis afforded the 13-acetylchlorin (1). Treatment of 1 with NBS afforded the 15-bromo analogue in 70% yield. Pd-mediated alpha-arylation closed the isocyclic ring to give the 13(1)-oxophorbine (2) in 85% yield. Facile access to 13(1)-oxophorbines should enable a variety of spectroscopic studies and diverse applications.",10.1021/jo0608265,2006-08-02,0.6017304493748294
Organic Letters,"Efficient Synthesis of Dissymmetric Malonic Acid <i>S</i>,<i>O</i>-Esters via Monoalcoholysis of Symmetric Dithiomalonates under Neutral Conditions","A novel method for the highly selective synthesis of dissymmetric S,O-malonates starting from symmetric diphenyl dithiomalonates under neutral conditions is described. The key step is the thermal formation of an acylketene, the stability of which would contribute to the selectivity. The synthetic utility of the dissymmetric S,O-malonates is also shown.",10.1021/ol201744u,2011-07-26,0.6017162719991754
Angewandte Chemie International Edition,Total Synthesis of Paecilomycine A,"Piecing together paecilomycine: The first total synthesis of paecilomycine A, a terpenoid that enhances nerve growth factor levels in certain human cells, has been achieved. Two highly stereoselective key steps in this concise route include an intermolecular Diels–Alder reaction and an intramolecular Pauson–Khand reaction (see scheme).",10.1002/anie.200605058,2007-02-15,0.6017124998057867
Journal of Organic Chemistry,Total Synthesis of (+)-Muconin,"(+)-Muconin (1), isolated from the leaves of Rollinia mucosa (Jacq.) Baill. (Annonaceae), is a sequential THF/THP-possessing acetogenin that exhibits potent and selective in vitro cytotoxicity toward pancreatic and breast tumor cell lines. In this study, a new route was established for obtaining (+)-muconin (1) starting with (-)-muricatacin (2), a compound recently synthesized via the novel alpha-C-H hydroxyalkylation and alpha'-C-H oxidation of tetrahydrofuran.",10.1021/jo0303721,2004-02-24,0.6017084233562704
Organic Letters,Total Synthesis of (–)-Sessilifoliamide C and (–)-8-<i>epi</i>-Stemoamide,"A convergent route featuring [3,3]-sigmatropic rearrangements of a linchpin azepinopyrrolidine served to install two of the four contiguous stereocenters present in the tricyclic Stemona alkaloids sessilifoliamide and stemoamide. In addition to the first total synthesis of (-)-sessilifoliamide C, a potential biosynthetic relationship between the sessilifoliamides and previously reported Stemona alkaloids is presented.",10.1021/ol200743u,2011-04-21,0.6016869575954931
Journal of Organic Chemistry,"An Alternative Synthesis of 1,1′-Bis-valienamine from <scp>d</scp>-Glucose","An alternative synthesis of 1,1'-bis-valienamine 5, which was demonstrated to be a potent trehalase inhibitor, has been achieved from d-glucose in 12 steps with 15% overall yield via enone 12 as the key intermediate, involving a direct aldol reaction of a glucose-derived diketone and a palladium-catalyzed allylic coupling reaction as the key steps.",10.1021/jo100474p,2010-04-14,0.6016777438560079
Organic Process Research & Development,Streamlined Atom-Economical Synthesis of Escitalopram: Kilogram-Scale Process Optimization and Industrial-Scale Implementation,"A straightforward, efficient, atom-economical, and scalable commercial manufacturing process was developed for the treatment of depression via commercial available starting materials. Citalopram, a selective serotonin reuptake inhibitor introduced in 1989, is a racemic mixture whose entire inhibitory activity resides in the S-(+)-enantiomer, also known as escitalopram. While the original six-step route suffered from sub-30% overall yield, inefficient diol resolution (<40%), nonrecyclable solvents, and problematic reaction byproduct management, our redesigned process achieves three critical advancements: (1) controlled impurity profiles, enhanced reaction efficiency (over 90% yield per step), streamlined postprocessing and recyclable solvents for preparation of racemic diol; (2) effective stereoinvertive cyclization strategy for converting R-diol byproducts into escitalopram via S N 2; (3) closed-loop resolution agent recovery and valorization of escitalopram enantiomeric byproduct. Safety-optimized scale-up enabled production of 446 kg batches with exceptional purity (>99.7%), enantiomeric excess (>99.8% ee), and 81.6% overall yield─representing 3.9-fold process intensification versus legacy methods. This sustainable platform demonstrates unprecedented atom utilization efficiency (>90%) while eliminating stereochemical waste, establishing new benchmarks for escitalopram manufacturing.",10.1021/acs.oprd.5c00188,2025-09-19,0.601676685666988
Organic Letters,Enantioselective Total Synthesis of (+)-Reserpine,"A catalytic, enantioselective synthesis of (+)-reserpine is reported. The route features a highly diastereoselective, chiral catalyst-controlled formal aza-Diels-Alder reaction between a 6-methoxytryptamine-derived dihydro-β-carboline and an enantioenriched α-substituted enone to form a key tetracyclic intermediate. This approach addresses the challenge of setting the C3 stereogenic center by using catalyst control. Elaboration of the tetracycle to (+)-reserpine includes an intramolecular aldol cyclization and a highly diastereoselective hydrogenation of a sterically hindered enoate.",10.1021/ol400046n,2013-01-18,0.6016656933837677
Tetrahedron,A new route to iodine-labeled N-isopropyl iodoamphetamine via organoboranes,,10.1016/s0040-4039(00)83894-0,1986-01-01,0.601664634466677
Organic Letters,One-Pot Relay Gold(I) and Brønsted Acid Catalysis: Cyclopenta[<i>b</i>]annulation of Indoles via Hydroamination/Nazarov-Type Cyclization Cascade of Enynols,"An expedient relay gold(I) and Brønsted acid catalyzed hydroamination/Nazarov cyclization of 1-(2-aminophenyl)pent-4-en-2-ynols for the synthesis of various polyfunctionalized cyclopenta[b]indoles is described. The synthetic utility of this method has been demonstrated by the synthesis of a few unprecedented pentacyclic indoles and indole-steroidal hybrids. Further, the new methodology has been successfully applied to the enantioselective synthesis of core carbon structure of the polyveoline family of natural products.",10.1021/acs.orglett.5b02632,2015-10-05,0.60166113871429
Journal of the American Chemical Society,Enantioselective Synthesis of (−)-Terpestacin and (−)-Fusaproliferin:  Clarification of Optical Rotational Measurements and Absolute Configurational Assignments Establishes a Homochiral Structural Series,"An enantioselective synthesis of the syncytium formation inhibitor (-)-terpestacin (1, 19 steps, 5.8% yield from the allylation product of (R,R)-pseudoephedrine propionamide, 3) and the fungal metabolite (-)-fusaproliferin (2, 21 steps, 5.3% yield from 3) in their natural configurations is described. The route employs a series of stereoselective enolate alkylation reactions to establish the initial stereogenic center, set the quaternary carbon configuration, close the 15-membered ring, and introduce the side-chain residue with proper stereocontrol. Careful analysis of our synthetic materials alongside natural samples has revealed that several errors were made in the earlier measurements of optical rotation or in the absolute stereochemical assignments of these natural products. Clarifying all discrepancies, we show here that natural terpestacin (1) is levorotatory, not dextrorotatory as originally described, but was correctly assigned as the (1S,11S,15R,23S)-enantiomer. Fusaproliferin (2) is levorotatory, as reported, but is in fact the (1S,11S,15R,23S)-enantiomer and not the antipodal configuration originally assigned.",10.1021/ja020072l,2002-03-23,0.6016583340515946
Organic Letters,"Total Synthesis of the Highly Potent Anti-HIV Natural Product Daurichromenic Acid along with Its Two Chromane Derivatives, Rhododaurichromanic Acids A and B",[reaction: see text] The highly potent anti-HIV natural product daurichromenic acid was successfully synthesized in only five steps with 49% overall yield. The key step in the synthetic strategy involves a microwave-assisted tandem condensation and intramolecular S(N)2'-type cyclization to form the 2H-benzopyran core structure.,10.1021/ol030109m,2003-10-22,0.6016581078132796
Journal of Organic Chemistry,"Highly Enantioselective Ir-Catalyzed Hydrogenation of Pyrazolo[1,5-<i>a</i>]pyrimidine for the Synthesis of Zanubrutinib","A highly enantioselective catalytic reduction of pyrazolo[1,5- a ]pyrimidine to zanubrutinib has been realized by the Ir/( R )- t -Bu-FcPhox complex. This chiral product could be obtained in up to >99% ee in the asymmetric transformation without any other additives, providing a new route for the asymmetric synthesis of zanubrutinib.",10.1021/acs.joc.3c02446,2024-01-23,0.6016525249770834
Synlett,A New Stereoselective Route to (-)-Octalactin A Based on Intramolecular SmI<sub>2</sub> Promoted Reformatsky Reaction,All articles of this category A novel stereoselective synthesis of the key left-hand fragment of (-)-octalactin A has been achieved from methyl ( R )-3-hydroxy-2-methylpropionate employing SmI 2 promoted intramolecular Reformatsky reaction of a δ-(bromoacetoxy)aldehyde as a key step. octalactin - enantioselective synthesis - eight-membered lactone - samarium(II) iodide - intramolecular Reformatsky reaction,10.1055/s-1998-1778,1998-07-01,0.6016519077274823
Journal of Organic Chemistry,"Short Total Synthesis of (±)-Gelliusine E and 2,3′-Bis(indolyl)ethylamines <i>via</i> PTSA-Catalyzed Transindolylation","A first and short total synthesis of the marine sponge 2,3'-bis(indolyl)ethylamine (2,3'-BIEA) alkaloid (±)-gelliusine E was performed in both a three-step divergent approach and a one-pot three-component approach with an overall yield of up to 58%. A key feature of the novel strategy is PTSA-catalyzed transindolylation of the readily synthesized 3,3'-BIEAs with tryptamine derivatives. The structure of the isolated natural product is revised as protonated (±)-gelliusine E (4'). By design, this modular route allows the rapid synthesis of other members of the 2,3'-BIEA family, for example, (±)-6,6'-bis-(debromo)-gelliusine F and analogues with step economy, operational simplicity, and reduced waste. Furthermore, their cytotoxicity in breast cancer cells was investigated.",10.1021/acs.joc.1c01461,2021-09-16,0.6016471643919047
Tetrahedron,"Diastereocontrolled reduction of cyclic β-enaminones. A new diastereoselective route to 2,6-disubstituted piperidines",,10.1016/s0040-4039(01)00770-5,2001-07-01,0.6016373453723928
Journal of Organic Chemistry,"Stereoselective Synthesis of Dihydrocoumarins via [1,2]-Phospha-Brook Rearrangement in Three-Component Coupling Reaction of α-Ketoesters, <i>o</i>-Quinone Methides, and Dialkyl Phosphites","A highly regio- and diastereoselective approach for the synthesis of phosphate substituted dihydrocoumarins via Brønsted base catalyzed [1,2]-phospha-Brook rearrangement is reported. The two-step, one-pot Michael addition of α-phosphonyloxy enolates proceeds by coupling of dialkyl phosphite and α-ketoesters to o -quinone methides, followed by an intramolecular cyclization, providing 3,4-dihydrocoumarin frameworks.",10.1021/acs.joc.1c01414,2021-10-12,0.6016308673488995
Organic Letters,Stereoselective Synthesis of Core Structure of Cortistatin A,"A stereoselective synthesis of the core structure of cortistatin A (1), a novel antiangiogenic steroidal alkaloid from Indonesian marine sponge, is described. An 8-oxabicyclo[3.2.1]octene system, a characteristic B-ring structure of 1, was elaborated by a 7-endo selective intramolecular Heck cyclization and a subsequent acid-mediated oxy-Michael reaction.",10.1021/ol201327u,2011-06-09,0.6016245798497024
Synthesis,A Simple Route to Chromone-2-carbonitriles,,10.1055/s-1983-30318,1983-01-01,0.6016144627517017
Tetrahedron,A simple route from dicyclopentadiene to trishomocubanone,,10.1016/s0040-4039(00)72073-9,1975-01-01,0.6016144627517017
Tetrahedron,A simple route to the indolizidine alkaloid skeleton,,10.1016/0040-4039(94)88452-8,1994-12-01,0.6016144627517017
Tetrahedron,A simple route from cyclopentadiene to hypostrophene,,10.1016/s0040-4039(01)82534-x,1974-01-01,0.6016144627517017
Tetrahedron,An unusually simple route to 4-demethoxy-7-deoxydaunomycinone,,10.1016/s0040-4039(00)94928-1,1985-01-01,0.6016144627517017
Tetrahedron,A simple route to β-aminomethylketones,,10.1016/j.tetlet.2004.09.122,2004-10-07,0.6016144627517017
Tetrahedron,A simple route to 3-(dihalomethylene)cyclo-alkenes,,10.1016/s0040-4039(00)87709-6,1982-01-01,0.6016144627517017
Tetrahedron,A simple route to cyclopentane annulation,,10.1016/s0040-4039(97)00912-x,1997-06-01,0.6016144627517017
Tetrahedron,A simple route to 3-furanyltrimethylsilane via hydromagnesiation,,10.1016/s0040-4039(00)81776-1,1983-01-01,0.6016144627517017
Organic Letters,"Selective Synthesis of Chiral Carbocycles by Iridium-Catalyzed Asymmetric Mono-, Double-, or Triple Hydrogenation of Cyclic Dienones","High Resolution Image Download MS PowerPoint Slide A divergent N,P-iridium-catalyzed asymmetric hydrogenation of cyclic dienones into chiral cyclohexenones, cyclohexanones, or cyclohexanols is described. The π-bonds in cyclic dienones underwent hydrogenation in a sequential manner, favoring the (s)- cis conformed alkene followed by the olefin in the (s)- trans conformation and at last the ketone, to install up to three stereocenters in a single step. The simple choice of the proper catalyst allowed the formation of each respective product in high yield and stereopurity (up to 99% ee, up to 99/1 d.r.). This protocol provides an interesting opportunity to access multiple and stereopure carbocycles starting from the same precursor that otherwise require multistep syntheses.",10.1021/acs.orglett.5c04476,2025-12-22,0.6016141942722565
Organic Process Research & Development,Development of a Practical Process for the Large-Scale Preparation of the Chiral Pyridyl-Backbone for the Crabtree/Pfaltz-Type Iridium Complex Used in the Industrial Production of the Novel Fungicide Inpyrfluxam,"Herein, we report the development activities leading to an efficient process for the large-scale production of the key intermediate to a crabtree/pfaltz-type iridium complex for industrial application. The process employs a highly efficient Suzuki coupling and a highly enantioselective transfer hydrogenation.",10.1021/acs.oprd.2c00097,2022-07-12,0.6016101080081351
Tetrahedron,Catalytic enantioselective synthesis of the second generation histamine antagonist cetirizine hydrochloride,,10.1016/0040-4039(96)00964-1,1996-07-01,0.6016069215700554
Organic Letters,Enantioselective Synthesis of 6/5-Spirosilafluorenes by Asymmetric Ring Expansion of 4/5-Spirosilafluorenes with Alkynes,A rhodium-catalyzed asymmetric ring expansion of 4/5-spirosilafluorenes with terminal alkynes has been developed using sterically demanding binaphthyl phosphoramidite ligand. The reaction is not only strategically distinct from cyclization or cycloaddition but also showcases the first enantioselective synthesis of axially chiral 6/5-spirosilafluorenes.,10.1021/acs.orglett.3c00346,2023-02-27,0.601599619644058
Synthesis,"Chemoenzymatic Synthesis of Methyl(6S)-(-)-6,8-Dihydroxyoctanoate: A Precursor to (R)-(+)-α-Lipoic Acid","All articles of this category A short synthetic sequence for the preparation of methyl (6 S )-(-)-6,8-dihydroxyoctanoate, the precursor to ( R)-(+)-α -lipoic acid is described starting from (2 S )-(+)-2-(tetrahydro-2-furyl)ethanol. Synthesis of the diol ester 11 S from (2 S )-(tetrahydro-2-furyl)ethanol obtained by a lipase mediated resolution",10.1055/s-1996-4256,1996-05-01,0.6015841488111773
Journal of the American Chemical Society,Total Synthesis Provides Strong Evidence: Xestocyclamine A is the Enantiomer of Ingenamine,"High Resolution Image Download MS PowerPoint Slide Xestocyclamine A ((−)- 1 ) is featured prominently in a biosynthesis pathway leading to a large family of polycyclic alkaloids. The first total synthesis now proves that the structure of this compound had originally been misassigned. The route to (−)- 1 is based on a double Michael addition for the formation of the bridged diazadecalin core and a palladium-catalyzed decarboxylative allylation to install the quaternary bridgehead center. Ring-closing alkyne metathesis allowed a 13-membered cycloalkyne to be forged, which was selectively reduced during an involved sequence of hydroboration/selective protodeborylation/alkyl-Suzuki coupling used to close the 11-membered ring. Crystallographic data prove the identity of synthetic (−)- 1 with nominal xestocyclamine, but the spectra differ from those of the authentic alkaloid. To clarify the point, the synthesis was redirected toward ingenamine ( 3 ), which is supposedly a positional isomer of 1 . The recorded data confirm the assignment of this particular natural product and strongly suggest that xestocyclamine A is in fact the enantiomer of ingenamine (+)- 3 .",10.1021/jacs.0c05347,2020-06-16,0.6015807296891813
Tetrahedron,Unusual ring opening of conjugated phenylcyclopropyl ketone; a new route to bicyclo[3:3:1] nonane intermediate,,10.1016/s0040-4039(00)93951-0,1976-01-01,0.6015794511624865
Angewandte Chemie International Edition,"Furo[3,2‐<i>b</i>]pyridine: A Privileged Scaffold for Highly Selective Kinase Inhibitors and Effective Modulators of the Hedgehog Pathway","Reported is the identification of the furo[3,2-b]pyridine core as a novel scaffold for potent and highly selective inhibitors of cdc-like kinases (CLKs) and efficient modulators of the Hedgehog signaling pathway. Initially, a diverse target compound set was prepared by synthetic sequences based on chemoselective metal-mediated couplings, including assembly of the furo[3,2-b]pyridine scaffold by copper-mediated oxidative cyclization. Optimization of the subseries containing 3,5-disubstituted furo[3,2-b]pyridines afforded potent, cell-active, and highly selective inhibitors of CLKs. Profiling of the kinase-inactive subset of 3,5,7-trisubstituted furo[3,2-b]pyridines revealed sub-micromolar modulators of the Hedgehog pathway.",10.1002/anie.201810312,2018-12-20,0.6015730422405707
Tetrahedron,The stereoselective synthesis of a key intermediate of the trinem antibiotic sanfetrinem,,10.1016/0040-4039(96)00682-x,1996-05-01,0.6015707311209831
Journal of Organic Chemistry,Synthesis of Functionalized Aromatic Oligomers from a Versatile Diphenylmethane Template,"An efficient synthesis of the functionalized diphenylmethane system 1 is described. Selective unmasking of the latent phenol groups on 1 allowed the introduction of various appendages onto the diphenylmethane scaffold via simple alkylation, Mitsunobu etherification, and transition-metal-mediated C−C bond formation. Conversion of 1 to iodide 18 and benzylic zinc reagent 28 followed by palladium(0)-mediated coupling of these derivatives provided homologue 29 . Repetitive application of this homologation protocol was used to prepare oligomers of chain length up to 16. Several examples of functional group manipulations on these higher order oligomers are presented. Diphenylmethane 1 was also employed as a key building block in the synthesis of the elastase inhibitor 67 . The potential application of extended aromatic oligomers to the field of drug discovery is discussed.",10.1021/jo970596h,1997-07-01,0.6015638960346626
European Journal of Organic Chemistry,Convergent Synthesis of Macrocyclic and Linear Desferrioxamines,"Polyhydroxamate desferrioxamines (DFO) are nontoxic siderophores endowed with high potential for development of therapeutic chelating agents. Herein, we report a modular and convergent strategy for diverse synthesis of macrocyclic and linear DFOs. The strategy employed orthogonally protected N ‐hydroxy‐ N ‐succinylcadaverine building blocks, which allowed bidirectional extension of the DFO structure. The efficiency of the new strategy was demonstrated by the total synthesis of 44‐membered macrocyclic DFO‐T 1 , as well as four related DFO compounds in 11–13 linear steps and 2.1 %–10 % overall yields. Comparison of the iron binding affinity of the DFOs revealed DFO‐E as the best chelator.",10.1002/ejoc.202000439,2020-05-22,0.6015475853658054
Synlett,A Pd-Mediated Approach to the Synthesis of an Unusual β-Hydroxytryptophan Amino Acid Constituent of Cyclomarin A,"A synthetic approach based on a palladium-mediated ­vinylation of indole derivatives was established for the preparation of 5, a key intermediate in the synthesis of N-(tert-butoxycarbonyl)-l-1H-[(R)-1,1-dimethyl-2,3-epoxypropyl]-β-hydroxytryptophan ethyl ester (6). Unsatisfying yields were obtained using N-alkyl-3-haloderivatives. The best method proved to be the oxidative coupling on 3-unsubstituted indole derivative.",10.1055/s-2006-941560,2006-05-22,0.6015469584672115
Angewandte Chemie International Edition,Total Synthesis of Aburatubolactam A,"An ocean of possibilities: Aburatubolactam A, a natural product isolated from the culture broth of a marine mollusk, was the target of a total synthesis (see scheme). Key transformations include tandem ring-opening/ring-closing metathesis, Lacey–Dieckmann cyclization, and macrolactamization.",10.1002/anie.200803593,2008-09-29,0.6015461510504195
Organic Process Research & Development,Selective Synthesis of a New Ascomycin Rearrangement Product (SDZ ASD732) on a Pilot Plant Scale,"The process for a pilot plant synthesis and the purification of a semisynthetic ascomycin derivative ( 1, SDZ ASD732) showing interesting biological activities is described. Conditions for the key transformation, a base-induced cascade of rearrangement and epimerization reactions of ascomycin leading to the selective formation of the new ascomycin derivative 1, were developed and successfully upscaled. Rapid screening of important reaction parameters was achieved by using automated parallel synthesis. In addition, a highly efficient purification process was found and implemented in the pilot plant process, resulting in an efficient separation of the semisynthetic ascomycin derivative from its by-products. The purification protocol consisted of preparative silica gel chromatography followed by a crystallisation step. Starting from crystalline ascomycin with a purity of ≥95%, an overall yield of 53% was achieved with a final purity of >98%.",10.1021/op000105m,2001-03-20,0.6015442768309852
Tetrahedron,Chemistry of aminophenols. Part 3: First synthesis of nitrobenzo[b]furans via a coupling–cyclization approach,,10.1016/s0040-4039(02)02333-x,2002-12-01,0.6015382842011933
Tetrahedron,Progress toward the total synthesis of maytansinoids. A facile route to the aromatic moiety (western zone),,10.1016/s0040-4039(01)92750-9,1977-01-01,0.6015208684877951
Angewandte Chemie International Edition,Benzo‐fused Nitrogen Heterocycles by Asymmetric Ring Expansion and Stereochemically Retentive Re‐contraction of Cyclic Ureas,"Benzo-fused nitrogen heterocycles are common features of bioactive molecules, and the enantioselective synthesis of their substituted analogues is an important goal. In this paper we demonstrate a practical and mechanistically intriguing approach to the enantioselective synthesis of 1-arylbenzazepines and their analogues. The reaction sequence starts with an asymmetric migratory ring expansion of indoline, tetrahydroquinoline, or tetrahydrobenzazepine ureas on treatment with a chiral lithium amide base. Treatment of the ring-expanded ureas with acid triggers a two-atom ring contraction-an 'azatropic shift' in which one urea nitrogen displaces the other-with almost complete retention of stereochemistry. Aminolysis of the urea products provides enantioenriched 1-aryl-tetrahydrobenzazepine derivatives and their congeners, including an analogue of an intermediate in the synthesis of the drug solifenacin. Deuteration, in situ IR, and DFT studies provide evidence for the mechanisms of the reaction steps.",10.1002/anie.202318417,2024-01-23,0.601516119649333
Journal of Organic Chemistry,BF<sub>3</sub>·OEt<sub>2</sub>-Mediated Highly Regioselective S<sub>N</sub>2-Type Ring-Opening of <i>N</i>-Activated Aziridines and <i>N</i>-Activated Azetidines by Tetraalkylammonium Halides,"A highly regioselective Lewis acid-mediated S(N)2-type ring-opening of N-sulfonylaziridines and azetidines with tetraalkylammonium halides in CH(2)Cl(2) solution to afford 1,2- and 1,3-haloamines in excellent yields is described. An easy diastereoselective route toward substituted chiral N-tosylaziridines has been developed. The mechanism of ring-opening via S(N)2 pathway has been confirmed by the formation of chiral haloamines with excellent er and dr. Chloroamines obtained from 2,3-disubstituted aziridines were converted to the chiral N-tosylamines via radical dehalogenation.",10.1021/jo902244y,2009-12-07,0.6014928530981666
Journal of Organic Chemistry,Stereoselective Arylation of Substituted Cyclopentenes by Substrate-Directable Heck–Matsuda Reactions: A Concise Total Synthesis of the Sphingosine 1-Phosphate Receptor (S1P<sub>1</sub>) Agonist VPC01091,"We describe herein an efficient and diastereoselective substrate-directable Heck-Matsuda reaction with nonactivated five-membered olefins. The carbamate acts as the main directing group in the arylation process allowing the synthesis of several functionalized aryl cyclopentenes in good to excellent diastereoselectivities (>85:15) and in isolated yields ranging from 41 to 90%. No double bond isomerizations were observed in these Heck reactions, and the newly created benzylic centers were preserved in all cases examined. The substrate directable Heck arylation approach was successfully applied in a straightforward total synthesis of the sphingosine 1-phosphate receptor-subtype 1 (S1P(1)) agonist VPC01091 by a concise and practical route involving 5 steps in 40% overall yield.",10.1021/jo3015209,2012-08-27,0.6014926204400757
Organic Process Research & Development,Development of a Scalable Synthesis of a Drug-Linker for ABBV-3373,"A scalable process to produce glucocorticoid-bearing drug-linker 1, utilized in the conjugation with the monoclonal antibody (mAb) adalimumab, has been developed. The route improves upon the first-generation approach through a more convergent assembly of the linker and warhead. Optimization and insights into the key transformations are discussed, including a challenging acetonide deprotection, acetal formation under strongly acidic conditions, and amide coupling and purification.",10.1021/acs.oprd.3c00447,2024-03-05,0.6014851593384121
Tetrahedron,Novel and efficient synthesis of 4-sulfonyl-2-pyridones,,10.1016/j.tetlet.2009.02.120,2009-02-22,0.6014717879099731
Synthesis,Synthetic Strategies Towards the Meroterpenoids Cochlearols A and B from Ganoderma cochlear,"Abstract Since the first reports of their isolation, the meroterpenoids cochlearol A and B have attracted interest from the synthetic community for their unique structural features. This review describes the attempted and successful total syntheses of these natural products and provides a summary of the strategies developed in the years since their isolation. 1 Introduction 2 Overview of Cochlearol A Syntheses 3 Tong’s Approach Towards Cochlearol A 4 Liu and Qin’s Total Synthesis of (±)-Cochlearol A 5 Ishigami’s Formal Synthesis of (±)-Cochlearol A 6 Chandrasekhar’s Formal Synthesis of (±)-Cochlearol A 7 Sugita’s Synthesis of (±)-Cochlearol B 8 Schindler’s Synthesis of (+)-Cochlearol B 9 Conclusions",10.1055/a-1878-7795,2022-06-20,0.6014676334514281
Tetrahedron,"Cyclotrimerization of 6-ethynylpurines. Synthesis of 1,2,4- and 1,3,5-tris(purin-6-yl)benzenes as novel Hoogsteen-triplet analogues",,10.1016/s0040-4039(00)01989-4,2001-01-01,0.601466739011486
Organic Process Research & Development,"From Milligram to Kilogram Manufacture of AZD4573: Making It Possible by Application of Enzyme-, Iridium-, and Palladium-Catalyzed Key Transformations","With the first generation medicinal chemistry synthesis as a starting point, we describe herein process development of AZD4573, an oncology drug candidate. In addition to improved yields and removal of chromatographic steps, we have addressed other factors such as availability of starting materials as well as safety of the chemistry involved. With several steps involving volatile, reactive, and non-UV active materials, reaction optimization was facilitated by implementing off-line 1 H NMR analysis of crude mixtures. Key transformations targeted for process development included a Wolff–Kishner reduction, an iridium-catalyzed borylation, and enzymatic resolution of a racemic amino-ester.",10.1021/acs.oprd.1c00058,2021-07-21,0.6014301785075946
Tetrahedron,"The synthesis and development of 2,5-disubstituted tetrahydrofurans as potential scaffolds for diversity-oriented synthesis",,10.1016/j.tetlet.2012.02.100,2012-03-05,0.6014296786246467
Tetrahedron,"Efficient synthesis of novel pyrido[3,2-d]pyrimidine-2,4-diones",,10.1016/s0040-4039(03)00273-9,2003-03-01,0.6014176552877487
Tetrahedron,An efficient synthesis of novel deoxy phospha sugar pyrimidine nucleosides,,10.1016/s0040-4039(03)00678-6,2003-04-01,0.6014176552877487
Journal of the American Chemical Society,A Rapid Synthesis of Hydroxymethylacylfulvene (HMAF) Using the Allenic Pauson−Khand Reaction. A Synthetic Approach to Either Enantiomer of This Illudane Structure,"An allenic Pauson−Khand reaction has been employed in the preparation of (±)-hydroxymethylacylfulvene (HMAF), an anticancer agent that is currently in Phase II clinical trials for a variety of solid tumor types. The synthesis is effected in 11 steps from commercially available starting materials. In addition, an asymmetric route to the title compound has been established by intersecting the racemic synthesis with an enantiomerically pure intermediate. The preparation of the enantiomerically pure intermediate involved the Sharpless asymmetric dihydroxylation (AD) of a trisubstituted olefin of an enyne system. This approach provides access to both enantiomers of HMAF simply by changing the ligands in the Sharpless AD reaction. Optimized conditions for the stereospecific synthesis of E or Z trisubstituted enynes from an aliphatic ketone using either Peterson olefination or Horner−Wadsworth−Emmons protocols are reported. Finally, a better understanding of the stereoelectronic requirements of the allenic P−K reaction is recognized.",10.1021/ja000546l,2000-05-01,0.6014159626515786
Synthesis,"Concise Asymmetric Synthesis of Deepoxyalchornoic Acid and (12R,13R)-Isoleukotoxin Diol","Abstract The first asymmetric synthesis and structural confirmation of deepoxyalchornoic acid have been accomplished from commercially available starting materials. Asymmetric dihydroxylation and Wittig olefination has been strategically executed to achieve a concise synthesis of deepoxyalchornoic acid and (12R,13R)-isoleukotoxin diol from a common intermediate chiral γ-lactone.",10.1055/a-2382-4650,2024-08-07,0.6014139973472896
Tetrahedron,Enantioselective synthesis of R-(−)-ligularenolide starting from S-(+)-carvone,,10.1016/s0040-4039(97)01757-7,1997-10-01,0.6014097800744675
Synlett,"A Concise, Asymmetric Synthesis of Methyl (1<i>S</i>,2<i>R</i>)-1-Amino-2,3-dihydro-1H-indene-2-carboxylate: A Novel, Constrained β-Amino Ester","All articles of this category The concise, asymmetric synthesis of methyl (1 S ,2 R )-1-amino-2,3-dihydro-1 H -indene-2-carboxylate is reported using a novel tandem conjugate addition, intramolecular electrophilic trap to construct the indane skeleton. β-amino acid - conjugate addition - lithium amide - cinnamate - ester enolate",10.1055/s-1999-2982,1999-12-01,0.6014093069427489
Tetrahedron,"Synthesis of novel 3-bromo-1,2-dihydroquinolines via palladium mediated intramolecular cyclization of N-tosyl-N-propargyl anilines",,10.1016/j.tetlet.2011.02.004,2011-02-07,0.6014042382410625
Journal of the American Chemical Society,The First Total Synthesis of Discorhabdin A,"The first stereoselective total synthesis of a potent antitumor alkaloid, discorhabdin A (1), which is a unique sulfur-containing pyrroloiminoquinone alkaloid, is described. The key step in the stereocontrolled total synthesis of 1 involves both a diastereoselective oxidative spirocyclization using a hypervalent iodine(III) reagent and an efficient construction of the labile and highly strained N,S-acetal skeleton. These methodologies provide a breakthrough in the total syntheses of these promising new antitumor agents, discorhabdins and their analogues, which should serve as valuable probes for structure-activity studies.",10.1021/ja0365330,2003-08-22,0.6014040727683538
Organic Letters,Dearomative Synthesis of Chiral Dienes Enables Improved Late-Stage Ligand Diversification,An efficient synthesis of chiral nonracemic diene ligands is facilitated by an enantioselective dearomative intermolecular arene cyclopropanation of anisole. The functionality of the resulting cycloheptatriene engenders distinct chemical environments in a downstream tricyclic bis(enol) triflate that permits selective late-stage functionalization. The synthesis of diverse C 1 - and pseudo - C 2 -symmetric dienes is therefore viable by iterative palladium-catalyzed cross-coupling reactions. The ligands provide moderate to high selectivities in known Rh(I)-mediated asymmetric transformations.,10.1021/acs.orglett.2c00183,2022-03-03,0.6013979729111524
Journal of Organic Chemistry,"Versatile Approach to Enantiopure 2,6-Disubstituted Piperidin-3-ol Framework:  Application to the Total Synthesis of (+)-Deoxoprosopinine","An efficient synthesis of enantiopure 2,6-disubstituted piperidin-3-ol 19 is developed featuring two key steps: (a). Julia olefination of (2R)-3-phenylsulfonyl-2-tert-butyloxycarbamoylpropanol benzyl ether 9B and (2R,3S)-2-tert-butyldiphenyl-3,4-O-isopropylidine-2,3,4-trihydroxybutyraldehyde 8 and (b). intramolecular N-alkylation. A straightforward asymmetric synthesis of (+)-deoxoprosopinine(2) from 19 is described demonstrating the versatility of this novel approach.",10.1021/jo0496291,2004-06-15,0.6013902411838289
Journal of Organic Chemistry,Second-Generation Synthesis of <i>syn</i>- and <i>anti</i>-Cycloheptadienylsulfone Polyketide Stereodiads,Stereodiad sulfones 18a and 18b are key intermediates for polyketide synthesis. This note describes the synthesis of 18a and 18b from enantiopure epoxide 2. The two sequences have been optimized for large-scale synthesis to give 80-85% overall yields in one operation (one operation implies that no crystallization or distillation is required throughout the synthesis) while avoiding chromatography.,10.1021/jo702353e,2008-03-19,0.6013872099635224
Tetrahedron,"A synthetic route to 1,3-dihydroisobenzofuran natural products: the synthesis of methyl ethers of pestacin",,10.1016/j.tetlet.2009.04.079,2009-04-25,0.6013784400240823
Organic Letters,Total Synthesis and Biological Evaluation of (−)-9-Deoxy-englerin A,"An effective total synthesis of (-)-9-deoxy-englerin (4), an analogue of the natural guaiane sesquiterpene englerin A (1), has been achieved. The synthesis features a transannular epoxide opening to construct the 5,7-fused ring system followed by transannular ether formation with mercury(II) trifluoroacetate.",10.1021/ol200499t,2011-03-17,0.6013667516383218
Journal of Organic Chemistry,Stereocontrolled Elaboration of Quaternary Carbon Centers through the Asymmetric Michael-Type Alkylation of Chiral Imines/Secondary Enamines:  Enantioselective Synthesis of (+)-Vincamine,"An enantioselective synthesis of (+)-vincamine ( 1 ) has been developed. The key strategic element was the stereocontrolled elaboration of a quaternary carbon center (future C-20 center of 1 ) by using the asymmetric Michael reaction involving chiral imines/secondary enamines under neutral conditions. Thus, addition of enaminolactam ( S )- 12, derived from ketolactam 7 (itself prepared in four steps from commercially available tryptamine) and ( S )-1-phenylethylamine, to methyl acrylate led, after hydrolytic workup, to adduct ( R )- 6 with a 90% stereoselectivity. The critical removal of the additional keto group of 6 was then examined. After extensive experimentation, we finally established that the most efficient deoxygenation procedure was the Wolff−Kishner reduction of the corresponding keto acid, which proceeded with a 55% yield. The cornerstone [ABD]-tricyclic lactam ester 38 thus obtained was next cyclized under Bischler−Napieralski reaction conditions to afford, after catalytic hydrogenation of the intermediary iminium perchlorate salt, a mixture of the desired, known indoloquinolizidine 5 and its epimer 39, in a ratio of 6:1, respectively. Basic treatment of 5 led to (+)-homoeburnamonine 4, which was finally converted, according to a known procedure, into our goal (+)-vincamine ( 1 ). Thus, synthesis of (+)-vincamine ( 1 ) has been achieved by a linear sequence of 15 chemical operations, starting from tryptamine, with an overall yield of 1.2%.",10.1021/jo9622690,1997-06-13,0.6013659287693351
Tetrahedron,A new stereocontrolled synthesis of d-ring aromatic steroid,,10.1016/s0040-4039(01)95393-6,1979-01-01,0.6013647104991735
Organic Letters,From Silphinenes to Penifulvins: A Biomimetic Approach to Penifulvins B and C,"The biomimetic total synthesis of penifulvins B and C uses a meta-photocycloaddition as a key step which gives rapid access to the fenestrane-type carboskeleton with control of an onring quaternary stereocenter. The route is concise, stereocontrolled, scaleable, and flexibile and requires only one protecting group.",10.1021/ol902594b,2009-12-09,0.6013560469480358
Journal of Organic Chemistry,"FeCl<sub>3</sub>·6H<sub>2</sub>O, a Catalyst for the Diastereoselective Synthesis of <i>cis</i>-Isoxazolidines from <i>N</i>-Protected δ-Hydroxylamino Allylic Acetates","An ecofriendly and diastereoselective synthesis of cis-3,5-disubstituted isoxazolidines through the FeCl3·6H2O-catalyzed cyclization of δ-hydroxylamino allylic acetates is described. The synthetic potential of these products is highlighted by the preparation of several functionalized 1,3-amino alcohol precursors.",10.1021/jo401627p,2013-09-12,0.6013557367824809
Journal of Organic Chemistry,"Access to 3-Sulfonamidoquinolines by Gold-Catalyzed Cyclization of 1-(2′-Azidoaryl)propargylsulfonamides through 1,2-<i>N</i>Migration","We describe a gold-catalyzed cyclization of 1-(2′-azidoaryl)propargylsulfonamides for the synthesis of 3-sulfonamidoquinolines, featuring a rare and highly selective 1,2- N migration. The key α-imino gold carbene intermediate is generated through an intramolecular nucleophilic attack of the azide group to the Au-activated triple bonds in a 6-endo-dig manner.",10.1021/acs.joc.1c02450,2021-12-20,0.6013542062884066
Synlett,"Concise Syntheses of (7Z,11Z,13E)-Hexadecatrienal and (8E,18Z)-Tetradecadienal","Concise and efficient syntheses of (7Z,11Z,13E)-hexadecatrienal, a sex-pheromone component of the citrus leaf miner, and (8E,10Z)-tetradecadienal, the sex pheromone of the horse-chestnut leaf miner were described, starting from the commercially available acetylene and acrolein. The stereoselective formation of E,Z-conjugated double bond relied on cross-coupling between Grignard reagent and (E,Z)-bromodiene. The present syntheses achieved high overall yield (26% of the former and 23% for the latter) and high isomeric purity (97% for the former and 99% for the latter).",10.1055/s-0031-1290338,2012-02-08,0.6013419076828678
Organic Letters,A Facile Synthetic Approach to 7-Deazaguanine Nucleosides via a Boc Protection Strategy,"An efficient route to the preparation of 5-substituted 2-amino-7-((2R,4R,5R)-tetrahydro-4-hydroxy-5-(hydroxymethyl)furan-2-yl)-3H-pyrrolo[2,3-d]pyrimidin-4(7H)-one compounds has been developed by the condensation of omega-substituted aldehydes with 2,6-diaminopyrimidin-4(3H)-one, followed by Boc protection to afford the corresponding N(2),N(2),N(7)-tris-Boc-O(4)-t-Bu-5-substituted 2-amino-3H-pyrrolo[2,3-d]pyrimidin-4(7H)-one, which is amenable to direct condensation with 1-chloro-2-deoxy-3,5-di-O-p-toluoyl-alpha-D-erythro-pentofuranose. This route affords an efficient synthesis to 2-amino-3H-pyrrolo[2,3-d]pyrimidin-4(7H)-one, 2-amino-5-alkyl-3H-pyrrolo[2,3-d]pyrimidin-4(7H)-one, and guanine nucleosides.",10.1021/ol9007537,2009-05-07,0.601339075452016
Angewandte Chemie International Edition,A General Sultone Route to the Pamamycin Macrodiolides—Total Synthesis of Pamamycin‐621A and Pamamycin‐635B,"Sultones swing again: The first total syntheses of the title antibiotics (see scheme) were achieved by application of sultone methodology. Since the final lactonizations with formation of the ester linkage between C1′ and the oxygen substituent on C8 proceeded with complete epimerization at C2′, the more readily available C2′ epimeric smaller fragments could be used for streamlining the synthetic sequence.",10.1002/anie.200501511,2005-09-07,0.6013377756351231
Tetrahedron,Stereoselective synthesis of the core structure of the protein phosphatase inhibitor dysidiolide,,10.1016/s0040-4039(98)00702-3,1998-06-01,0.6013318570093148
Synthesis,A Practical Approach to 6H-Indol-6-ones Enables the Formal Synthesis of γ-Lycorane,"Abstract We represented herein a two-step synthesis of 1-methyl-6H-indol-6-one which is an N-containing 6/5 fused bicyclic building blocks in Amaryllidaceae alkaloids. The key step featured is a ‘one-pot’ ozonolysis/reductive amination/cyclization of allylated cyclohexa-1,3-dione to give bicyclic compounds. Moreover, the formal total synthesis of natural product γ-lycorane could be achieved through a photo-promoted cyclization/oxidation cascade reaction from the resulting bicyclic intermediate.",10.1055/a-1878-8597,2022-06-20,0.6013286459168395
Tetrahedron,A new route to 2-aryl-4-quinolones via palladium-catalyzed carbonylative coupling of o-iodoanilines with terminal arylacetylenes,,10.1016/s0040-4039(00)74135-9,1992-01-01,0.6013279662914821
Angewandte Chemie International Edition,Enantioselective Synthesis of (+)‐Monobromophakellin and (+)‐Phakellin: A Concise Phakellin Annulation Strategy Applicable to Palau'amine,"A unique oxidative cyclization of a tricycle bearing a guanidine aminal provides a concise route to the enantioselective synthesis of (+)-phakellin and (+)-monobromophakellin in nine and ten steps, respectively, starting from L-proline (see scheme). This sequence provides a simple annulation strategy applicable to the preparation of more complex members of this family of marine sponge-derived alkaloids including palau'amine.",10.1002/anie.200703998,2008-01-03,0.601322451290439
Synthesis,Synthesis of Polyalkylated Indoles Using a Thallium(III)-Mediated Ring-Contraction Reaction,"A new approach to the synthesis of cyclopenta[g]indole derivatives possessing structural features of natural alkaloids, such as trikentrins and herbindols, is described. The key step in the sequence is a thallium(III)-mediated ring-contraction reaction to transform a cyclohexene moiety into a functionalized cyclopentyl unit.",10.1055/s-2007-990907,2007-12-01,0.6013184304566573
Synlett,Total Synthesis of Amphidinolide T3 Using Ring-Closing Metathesis and Asymmetric Dihydroxylation Strategy,"Total synthesis of amphidinolide T3, a 19-membered ring marine macrolide, has been accomplished using a ring-closing metathesis (RCM) and asymmetric dihydroxylation (AD) strategy. A cycloalkene having the C12=C13 double bond was assembled via RCM in 80% yield and in E/Z ratio of 76:24. The (12E)-isomer -underwent AD using 1 mol% K<sub>2</sub>OsO<sub>2</sub>(OH)<sub>4</sub> and 4 mol% (DHQD)<sub>2</sub>AQN as the chiral catalyst at 0 C for 15 hours, furnishing the desired (12R,13R)-diol and its (12S,13S)-diastereomer in 59% and 25% yields, respectively. Selective monosilylation of (12R,13R)-diol followed by DMP oxidation and desilylation afforded amphidinolide T3 in 3.4% overall yield via a 15-step sequence.",10.1055/s-0030-1259706,2011-03-08,0.6013027968034489
Journal of Organic Chemistry,Asymmetric Synthesis of Tetrabenazine and Dihydrotetrabenazine,"The enantioselective synthesis of (+)-tetrabenazine (TBZ) and (+)-dihydrotetrabenazine (DTBZ), agents of significant interest for therapeutic and molecular imaging applications, has been completed in 21% (TBZ) and 16% (DTBZ) overall yield and in >97% ee from the starting dihydroisoquinoline. The synthesis utilizes Sodeoka's palladium-catalyzed asymmetric malonate addition to set the initial stereocenter followed by a number of diastereoselective transformations to incorporate the remaining asymmetric centers.",10.1021/jo900480n,2009-04-17,0.6012984149381277
Tetrahedron,A norbornyl route to some novel seven-membered iminocyclitols,,10.1016/s0040-4039(01)02124-4,2002-01-01,0.6012974175381812
Angewandte Chemie International Edition,Synthetic Studies on Chartelline C: Stereoselective Construction of the Core Skeleton,"What a core-ker! The title synthesis was achieved using a route featuring an intramolecular Mitsunobu reaction of a nosyl amide, stereoselective construction of the β-lactam, and formation of an enamide moiety by selenoxide elimination. The stereochemistry of the alkylation for the formation of the β-lactam was controlled by a secondary hydroxy group on the ten-membered ring. SEM=2-(trimethylsilyl)ethoxymethyl; TBS=tert-butyldimethylsilyl.",10.1002/anie.201204726,2012-08-02,0.601291469317546
Journal of Organic Chemistry,"Diastereoselective Syntheses of Deoxydysibetaine, Dysibetaine, and Its 4-Epimer","(+/-)-Deoxydysibetaine 2 and 4-epi-dysibetaine 3 were prepared in a few steps from methyl pyroglutamate through a regioselective Mannich reaction at C-2. Natural (2S,4S)-dysibetaine 1, a sponge metabolite isolated from Dysidea herbacea, and (2S)-2 were synthesized from enantiopure (S)-pyroglutaminol with very high stereoselectivity. The key steps were an original formation of stereogenic quaternary center C-2 and the diastereoselective hydroxylation at C-4.",10.1021/jo040216+,2004-09-29,0.601290012395248
Journal of Organic Chemistry,Enantioselective Total Synthesis and Biological Evaluation of (+)-Kibdelone A and a Tetrahydroxanthone Analogue,The total synthesis of kibdelone A has been accomplished via In(III)-catalyzed arylation of a heterocyclic quinone monoketal and iodine-mediated oxidative photochemical electrocyclization for construction of the ABCD ring moiety. Enzymatic dihydroxylation of methyl 2-halobenzoate substrates was employed for synthesis of activated 2-halo-cyclohexene F-ring fragments. A one pot oxa-Michael/Friedel-Crafts process allowed access to the first simplified DEF ring analogues of the kibdelones.,10.1021/jo401169z,2013-07-08,0.6012753160647144
Synlett,Synthesis of Conformationally Locked Methanocarba-uridine as a Precursor for Nucleotides Agonizing P2Y<sub>6</sub> Receptor,"Conformationally locked uridine in the ‘southern’ conformation, which could be an important precursor for corresponding nucleotides, was stereoselectively synthesized. Southern uridine nucleotides are expected to be full agonists for the P2Y6 receptor. Poor diastereoselectivity in the osmium-mediated dihydroxylation on the allyl amine was overcome by introduction of an allyl azide on which osmium medium hydroxylation, and subsequent cyclization yielded 6-oxabicyclo[3.2.0]heptane in a 9:1 ratio. High regio­selectivity between the 2′- and 3′-hydroxyl groups in the intramolecular O-alkylation and construction of uracil moiety from the azido group provided the final target, a southern 2′-benzoylated uridine derivative.",10.1055/s-2007-973902,2007-04-01,0.601269375446146
Synthesis,Practical and Efficient Synthesis of Polyaryl(hetaryl)-Substituted Cyclohexenones and Salicylates,"A new efficient method was developed for the synthesis of triaryl-substituted cyclohexenones and salicylates. The method is based on the Robinson annulation of readily available keto esters and chalcones, followed by the aromatization of the cyclohexenone moiety. The aromatization can be accomplished either by reaction with bromine in boiling chloroform or bromination with copper(II) bromide in ethanol followed by treatment with pyridine or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). The new synthetic method was also implemented in a one-pot protocol, which in some cases resulted in higher yields of the final product compared to those obtained in the stepwise synthesis.",10.1055/s-0036-1588908,2016-11-24,0.6012679877868566
Journal of the American Chemical Society,Total Synthesis of Salinosporamide A,"Total synthesis of potent proteasome inhibitor salinosporamide A (1) has been accomplished, which features strictly substrate-controlled operations starting with the only chiral center of (R)-pyroglutamic acid. The consecutive quaternary carbons within 1 have been efficiently constructed by manipulation of two intramolecular reactions: (1) carbonate-mediated internal acylation of imidate ester (4 --> 14) and (2) selenocyclization of aldehyde to exocyclic methylene group (5 --> 18).",10.1021/ja0522783,2005-05-19,0.6012621272289063
Synthesis,A Convenient Synthesis of Novel Pyrimidinyl-5′-nor-1′-homocarbanucleosides Based on Indanol,"Starting from (±)-cis-3-hydroxymethyl-1-indanol, novel pyrimidinyl-5′-nor-1′-homocarbanucleosides were synthesized through a key coupling reaction with pyrimidine bases (Mitsunobu reaction for uracil and thymine, and nucleophilic substitution on a mesylate for cytosine). The uracil derivative was 5-halogenated by treatment with N-chloro- or N-bromosuccinimide.",10.1055/s-2005-918420,2005-01-01,0.6012586623020916
Angewandte Chemie International Edition,Synthesis of Each Enantiomer of Rocaglamide by Means of a Palladium(0)‐Catalyzed Nazarov‐Type Cyclization,A recently reported Pd(0)-catalyzed asymmetric Nazarov-type cyclization has been successfully applied in the key step of the first catalytic asymmetric total synthesis of (-)-rocaglamide (natural) and (+)-rocaglamide. The stereochemistry at the C3 position that controls the stereochemistry of all other stereocenters is determined in the cyclization step. This versatile and modular synthesis proceeds from simple reagents.,10.1002/anie.201501374,2015-03-30,0.6012578153770967
Synlett,Enantioselective Palladium-Catalyzed Decarboxylative Dearomative Asymmetric Allylic Alkylation of Benzofurans: Diversity-Oriented Synthesis of Flavaglines,"Abstract With the introduction of new Trost-type bisphosphine ligands bearing a chiral cycloalkane framework, the highly efficient and enantioselective palladium-catalyzed decarboxylative dearomative asymmetric allylic alkylation (AAA) of benzofurans was achieved. This enabled a diversity-oriented synthesis (DOS) of previously unreachable flavaglines, which features two diversification stages. A new avenue for developing flavagline-based drugs was thus established. 1 Introduction 2 The Dearomative Asymmetric Allylic Alkylation of Benzofurans 3 Synthesis of Flavaglines 4 Conclusion and Outlook",10.1055/a-1650-4266,2021-09-21,0.6012476347167435
Tetrahedron,Improved synthesis of α-Methylene-γ-lactones organotin reagents,,10.1016/s0040-4039(00)85228-4,1986-01-01,0.601247081401276
Tetrahedron,"An efficient and highly regioselective synthesis of 4-deoxy- and 2-acetamido-2,4-dideoxy-β-d-threo-hex-3-enopyranosides",,10.1016/s0040-4039(02)00118-1,2002-02-01,0.6012343078486123
Organic Letters,Environmentally Responsible and Cost-Effective Synthesis of the Antimalarial Drug Pyronaridine,"Two routes to the antimalarial drug Pyronaridine are described. The first is a linear sequence that includes a two-step, one-pot transformation in an aqueous surfactant medium, leading to an overall yield of 87%. Alternatively, a convergent route utilizes a telescoped three-step sequence involving an initial neat reaction, followed by two steps performed under aqueous micellar catalysis conditions affording Pyronaridine in 95% overall yield. Comparisons to existing literature performed exclusively in organic solvents reveal a 5-fold decrease in environmental impact as measured by E Factors.",10.1021/acs.orglett.2c00944,2022-05-03,0.6012270073025815
Tetrahedron,Stereoselective radical annulation route to the synthesis of (±)-paulownin and (±)-isogmelinol,,10.1016/s0040-4039(00)61118-8,1992-09-01,0.6012266460517192
Organic Letters,Asymmetric Total Synthesis of (+)-Epiibogamine Enabled by Three-Component Domino Michael/Michael/Mannich Annulation of <i>N</i>-Sulfinyl Metallosilylenamines,"The iboga alkaloids are promising antiaddictive and neuroregeneration candidates for medical treatment. There is a lack of studies for C20-epi iboga alkaloids due to the synthetic difficulties. Herein we report the shortest total synthesis of (+)-epiibogamine in seven steps from trimethyl orthobutyrate. The novel N -sulfinyl silylenamine reagent enabled the key step, with three-component domino Michael/Michael/Mannich annulation providing the 1-amino-2,4-diester scaffold with four new chiral centers, and access to the isoquinuclidine in high yield (84%) and diastereoselectivity (>95:5 dr).",10.1021/acs.orglett.2c04287,2023-02-02,0.6011943438942937
Journal of Organic Chemistry,Synthetic Studies toward Bazzanin K: Regioselective and Chemoselective Three-Component Suzuki Coupling,"The terphenyl substructure of the chiral cyclophane natural product bazzanin K was constructed. The key step involved sequential Suzuki couplings of a nonsymmetric dibromobenzene, which can be performed as a two-step process or as a one-pot three-component coupling. The key step represented a regioselective coupling of a dibromobenzene, as well as a chemoselective coupling of phenyl bromides in the presence of phenyl chlorides. Terphenyl intermediates displayed atropdiastereoisomerism, and they were converted to a single phenanthrene target by way of ring-closing metathesis.",10.1021/acs.joc.9b02043,2019-08-26,0.6011935005214425
Synthesis,Synthesis of a Potential Precursor (Northern Fragment) for the Cyclic Depsipeptides Vioprolides A and C,"Abstract The synthesis of a potential northern fragment for the cyclic depsipeptides vioprolide A and vioprolide C is accomplished. The prepared compound is a pentapeptide and displays the non-canonical amino acid dehydrobutyrine (Dhb) at its C-terminal end. The central position is taken by another non-canonical amino acid, (2S,4R)-4-methylazetidine carboxylic acid (Maz). A route to enantiopure N-Boc-protected Maz (N-Boc-Maz) is developed from l-pyroglutamic acid, and this building block is taken into thiopeptide formation at its C-terminal end by successively coupling serine and threonine fragments. The C-terminal threonine is dehydrated to Dhb before attaching a d-Leu-Ala dipeptide to the N-terminal site of Maz. Several intermediates are directly telescoped into the next reaction step. Starting from N-Boc-Maz, the assembly of the pentapeptide is complete in eight steps with an overall yield of 16%.",10.1055/s-0043-1763750,2024-04-29,0.6011866378710434
Organic Letters,"Total Synthesis of Solandelactones E and F, Homoeicosanoids from the Hydroid <i>Solanderia </i><i>secunda</i>","Asymmetric total syntheses of solandelactones E and F confirmed that hydroxyl configuration at C11 in these oxylipins had been misassigned and that the stereochemistry at this center should be reversed. Key steps in the synthesis involved a Nagao asymmetric acetate aldol reaction, a directed Simmons-Smith cyclopropanation, a Holmes-Claisen rearrangement to establish the unsaturated octalactone, and a Nozaki-Hiyama-Kishi coupling to connect two major fragments at C11-C12.",10.1021/ol701564x,2007-07-21,0.6011863294958495
Journal of Organic Chemistry,Stereoselective Synthesis of Maralixibat via VO(acac)<sub>2</sub>/Schiff Base-Catalyzed Asymmetric Oxidation of Its Sulfide Intermediate,"The stereoselective synthesis of maralixibat was achieved by harnessing the chiral transferring effect of the stereogenic R -sulfoxide functionality, which was obtained via the VO(acac) 2 /Schiff base-catalyzed asymmetric oxidation of a phenylthiophenol prochiral intermediate. The R -sulfoxide intermediate underwent a ring closure reaction to form the seven-membered ring core structure with the desired stereochemistry, ultimately ensuring the drug’s exceptional isomeric purity and synthetic efficiency.",10.1021/acs.joc.4c01443,2024-09-18,0.6011828910861787
Journal of Organic Chemistry,Synthesis of Polyprenylated Acylphloroglucinols Using Bridgehead Lithiation:  The Total Synthesis of Racemic Clusianone and a Formal Synthesis of Racemic Garsubellin A,"The synthesis of polyprenylated phloroglucinol natural products, including clusianone, nemorosone, and garsubellin A, was pursued by a strategy involving construction of a core bicyclo[3.3.1]nonanetrione structure and subsequent elaboration via organolithium intermediates. Appropriate bridged core structures were obtained through the cyclization of a suitably substituted cyclohexanone enol ether or enol silane with malonyl dichloride. Additional substituents were then introduced by means of regioselective lithiation reactions, including the generation of bridgehead enolates, thus enabling the total synthesis of clusianone and also of an advanced intermediate toward nemorosone. In the case of garsubellin A, an additional THF-like ring was elaborated by a biomimetic 5-exo-tet cyclization of an enol ether (or enol) with a side-chain epoxide. This enabled a formal synthesis of racemic garsubellin A by accessing one of the late intermediates in the Danishefsky synthesis.",10.1021/jo070388h,2007-05-26,0.6011715307132232
Journal of the American Chemical Society,Enantioselective Total Synthesis of (−)-Novofumigatonin,"We disclose the first and enantioselective synthesis of novofumigatonin, an ortholactone meroterpenoid natural product featuring an unprecedented 7/6/5/6/5/5 hexacyclic skeleton. On a strategic level, this was addressed by a highly convergent strategy that hinges on coupling of a complex neopentylic organolithium reagent and a highly hindered ketone. A unique approach to the ortholactone-acetal was required as it is not peripheral but embedded within the complex carbocyclic framework. This key challenge was addressed by orchestration of a condensation cascade triggered by the selective generation of an oxocarbenium ion. Tempering reactivity in the face of the densely functionalized skeleton proved key and culminated in the total synthesis of novofumigatonin. Of note, this represents the first study on the construction of such an embedded ortholactone, potentially useful for preparation of such motifs in the context of complex molecule synthesis.",10.1021/jacs.5c10466,2025-08-20,0.6011704632753053
Organic Letters,"First Asymmetric Total Syntheses of (−)-Subincanadines A and B, Skeletally Rearranged Pentacyclic Monoterpenoid Indole Alkaloids in <i>Aspidosperma </i><i>s</i><i>ubincanum</i>","We achieved the first asymmetric total syntheses of novel Aspidosperma indole alkaloids, (-)-subincanadines A and B, which involve an intramolecular diastereoselective Pictet-Spengler cyclization and an intramolecular Nozaki-Hiyama-Kishi reaction as key steps in the total syntheses.",10.1021/ol061908i,2006-09-01,0.6011681316614071
European Journal of Organic Chemistry,Hydroxylation of Eleuthoside Synthetic Intermediates by P450<sub>BM3</sub> (CYP102A1),"A seven‐step synthesis of the first tricyclic intermediate in Danishefsky's total synthesis of eleutherobin is reported with Wittig homologation and sequential additions of metallated furan derivatives to aldehydes as key steps. Aiming to prepare hydroxylated eleutherobin analogues for cytotoxicity screening, the furan diol epimers 6 and precursors 1 and 2 were exposed to a 48‐member panel of engineered cytochrome P450 BM3 variants. Both furan‐containing substrates reacted solely at the furan ring, one resulting in overall biocatalytic Achmatowicz reaction. Selective hydroxylation at four separate sp 3 C–H centres was achieved in the substrates lacking the furan component. P450 BM3 ‐catalysed hydroxylation of racemic substrates can proceed with kinetic resolution; in the case reported here, the 2°‐allylic alcohol product 10 was generated with an 82:18 enantiomeric ratio.",10.1002/ejoc.201801206,2018-09-19,0.6011635188050809
Synlett,Synthetic Study towards Strictamine: The Oxidative Coupling Approach,"A synthetic approach featuring a key intramolecular oxidative coupling of a dianion for the formation of the C7–C16 bond was exploited aiming at the synthesis of strictamine. Treatment of substituted tetrahydrocarboline with LHMDS at –78 °C followed by iodine at room temperature afforded a tetracyclic compound, a substructure of eburnane-type alkaloid, via the formation of the ­N a –C16 bond.",10.1055/s-0033-1339472,2013-08-07,0.6011601790771056
Tetrahedron,Studies on the total synthesis of fredericamycin A: Development of an intermolecular alkyne-chromium carbene complex cyclization approach to the ABCDE ring system,,10.1016/s0040-4039(01)93705-0,1989-01-01,0.6011571606273137
Organic Letters,A Short Synthesis of (±)-Epiasarinin,"[reaction: see text] Epiasarinin, an endo-endo furofuran, has been synthesized from piperonal via a five-step route with good stereocontrol. The sequence involves Darzens condensation, alkenyl epoxide-dihydrofuran rearrangement, and a Lewis acid mediated cyclization.",10.1021/ol025569e,2002-03-14,0.6011529212474447
Tetrahedron,Optimisation of a key cross-coupling reaction towards the synthesis of a promising antileishmanial compound,"During the course of a research program aimed at identifying novel antileishmanial compounds, a multi-gram synthesis of N-(trans-4-((4-methoxy-3-((R)-3-methylmorpholino)-1H-pyrazolo[3,4-d]pyrimidin-6-yl)amino)cyclohexyl)-2-methylpropane-1-sulfonamide ((R)-1) was required. This letter describes optimisation of the reaction conditions and protecting group strategy for a key Buchwald-Hartwig coupling, delivering the required quantities of (R)-1, as well as further compounds in the series.",10.1016/j.tetlet.2019.03.068,2019-03-28,0.6011453187178608
Journal of Organic Chemistry,"Synthesis of Disubstituted 3-Phenylimidazo[1,2-<i>a</i>]pyridines via a 2-Aminopyridine/CBrCl<sub>3</sub> α-Bromination Shuttle","A versatile protocol for the synthesis of disubstituted 3-phenylimidazo[1,2- a ]pyridines by coupling 2-aminopyridine with phenylacetophenones, phenylacetones, or β-tetralone has been developed. Isolated yields of up to 97% were obtained at 80 °C within 5 h. The 2-aminopyridine/CBrCl 3 system acts as an α-bromination shuttle by transferring Br from CBrCl 3 to the α-carbon of the carbonyl moiety. This triggers a series of steps with double C–N/C–N bond formation to the final product. The distinct advantages of this protocol include the use of commercially available inexpensive substrates, simplicity of a metal-free one-pot synthesis, and ease of scale-up to multigram quantities.",10.1021/acs.joc.6b01714,2016-09-08,0.6011419366700859
Synthesis,The Total Synthesis of (+)-Petasin and (+)-Isopetasin,"All articles of this category Petasin 1 and isopetasin 2 , anti-inflammatory and analgesic components of the butterbur ( Petasites hybridus ), were prepared for the first time in a short and enantioselective synthesis. The key steps were a Michael addition/alkylation (78) , an enamine alkylation to give 9 and a cyclization with N -phenyliminoketenylidenetriphenylphosphorane 11 (1015). petasin - isopetasin - isopetasol - cumulated ylides - intramolecular Wittig reaction",10.1055/s-1997-1492,1997-01-01,0.6011406230506494
Synlett,Synthesis of Pyridine-stretched 2′-Deoxynucleosides,"Synthesis of novel pyridine-stretched nucleoside (PSN) analogues of adenine (strA) (1), 2,6-diaminopurine (strD) (15) and hypoxanthine (strH) (17) from 4(5)-nitroimidazole has been achieved. Glycosylation of 4(5)-nitroimidazole was optimized to give consistently good yields (>70%) of the desired analytically pure 5-nitro-1′-β isomer 8 which on hydrogenation, C-addition of ethoxymethylene malononitrile (EMMN) and cyclisation provides the key intermediate 14 for PSN synthesis.",10.1055/s-2002-33505,2002-01-01,0.6011173405193833
European Journal of Organic Chemistry,Synthesis of Spinosyn Analogues for Modern Crop Protection,"Abstract New spinosyn analogues 3 with an arene group as ring A and containing a L ‐rhamnose moiety have been prepared. The key step in the synthesis of 3 is a Pd‐catalyzed twofold Heck reaction of glycosylated bromoarene 4 , containing an iodovinyl side chain and a tri‐ O ‐methyl‐ L ‐rhamnose moiety with the cyclopentene‐annulated macrolactone 5 . Compounds 3 may be of interest as new insecticides.",10.1002/ejoc.201200600,2012-09-05,0.6011062560364132
Tetrahedron,"Synthesis of novel 5-monoalkylbarbiturate derivatives: new access to 1,2-oxazepines",,10.1016/j.tetlet.2015.10.108,2015-11-04,0.6011037433653794
Organic Letters,Efficient Synthesis of a Peculiar Vicinal Diamine Semiochemical from <i>Streptomyces natalensis</i>,"The pimaricin-inducing (PI) factor, produced by Streptomyces natalensis is a proposed pheromone with a peculiar vicinal diamine structure. The first synthesis of this molecule is reported. It features oxidative dimerization of an aci-nitro anion derived from tris(hydroxymethyl)nitromethane and disproportionation catalyst-facilitated hydrogenation of the resulting vicinal tertiary dinitro compound. As the synthesis requires only four steps with no chromatographic separations, it provides a convenient route to prepare PI factor for biological studies and industrial applications.",10.1021/ol1013763,2010-07-15,0.6010918604030819
Journal of Organic Chemistry,Total Synthesis of the Annonaceous Acetogenins Asiminocin and Asiminecin by a Bidirectional Approach,"A total synthesis of the Annonaceous acetogenins asiminocin and asiminecin is described. The approach is bidirectional starting from the ( S, S )-tartrate derived dialdehyde 7 and the ( R )-α-OSEM stannane 6 . Addition of 6 to 7 in the presence of InCl 3 afforded the bis-adduct, anti -diol 8 . The derived tosylate 9 was converted to the bis-tetrahydrofuran core unit 10 upon treatment with TBAF. Selective silylation of one of the two equivalent terminal diol groupings led to the OTBS ether alcohol 11 . Oxidation to aldehyde 12 and then InCl 3 -promoted addition of the ( S )-allylic stannane 14 gave the anti adduct 15 . Removal of the OH group by reduction of the tosylate 16 with LiBEt 3 H yielded the SEM ether 17 . Hydrogenation of the three double bonds of 17 followed by cleavage of the terminal silyl ether and oxidation afforded aldehyde 20 . Conversion to the vinylic iodide 21 followed by Pd(0)-catalyzed coupling with the ( S )-alkynyl butenolide 24 gave the asiminocin derivative 25 . Selective hydrogenation of the enyne moiety with diimide and cleavage of the SEM protecting groups completed the synthesis of asiminocin ( 27 ). Asiminecin ( 41 ) was prepared starting from aldehyde 12 and the OTBS allylic stannane 28 . Addition of the latter to the former in the presence of InCl 3 afforded the anti adduct 29 which was protected as the SEM ether 30 . Hydrogenation followed by OTBS cleavage with TBAF and selective silylation of the primary alcohol with TBSCl and Et 3 N−DMAP led to the secondary alcohol 33 . Tosylation and hydrogenolysis with LiEt 3 BH removed the C30 OTs group affording the SEM ether 35 . The remaining steps were carried out along the lines described for asiminocin via the vinyl iodide 38 which was coupled with acetylenic butenolide 24 to afford enyne 39 . Selective reduction with diimide and SEM cleavage completed the synthesis.",10.1021/jo970424k,1997-08-01,0.601086029103844
Chemical Science,Bio-inspired total synthesis of daphnepapytone A,"to give the guaiane skeleton. Oleodaphnone (3) was identified as a key intermediate of this strategy and was engaged in a biomimetic [2 + 2]-photocycloaddition, leading to the bridged cyclobutane of the title compound. Finally, a late-stage C-H oxidation chemoselectively released a triketone intermediate (15), which was reduced in a remarkably chemo- and stereoselective manner to furnish target compound 1. During this work, complex rearrangements of the bridged skeleton were observed. Beside the total synthesis of daphnepapytone A, this paper also describes the total synthesis of three guaiane natural products (oleodaphnone, diarthroncha C, daphnenicillata W), one of them being structurally revised.",10.1039/d5sc02953h,2025-01-01,0.6010857626611239
Journal of the American Chemical Society,"Synthesis and NMR Characterization of (<i>Z</i>,<i>Z</i>,<i>Z</i>,<i>Z</i>,<i>E</i>,<i>E</i>,ω)-Heptaprenol","We describe a practical, multigram synthesis of (2Z,6Z,10Z,14Z,18E,22E)-3,7,11,15,19,23,27-heptamethyl-2,6,10,14,18,22,26-octacosaheptaen-1-ol [(Z(4),E(2),ω)-heptaprenol, 4] using the nerol-derived sulfone 8 as the key intermediate. Sulfone 8 is prepared by the literature route and is converted in five additional steps (18% yield from 8) to (Z(4),E(2),ω)-heptaprenol 4. The use of Eu(hfc)(3) as an NMR shift reagent not only enabled confirmation of the structure and stereochemistry of 4, but further enabled the structural assignment to a major side product from a failed synthetic connection. The availability by this synthesis of (Z(4),E(2),ω)-heptaprenol 4 in gram quantities will enable preparative access to key reagents for the study of the biosynthesis of the bacterial cell envelope.",10.1021/ja306184m,2012-08-04,0.6010799101036669
Tetrahedron,A tandem oximation–cyclization route to Δ2-isoxazolines,,10.1016/j.tetlet.2007.07.146,2007-07-31,0.6010704249988548
Journal of Organic Chemistry,"A Practical Procedure for the Large-Scale Preparation of Methyl (2<i>R</i>,3<i>S</i>)-3-(4-Methoxyphenyl)glycidate, a Key Intermediate for Diltiazem","A practical synthesis of methyl (2R,3S)-3-(4-methoxyphenyl)glycidate (-)-2, a key intermediate for diltiazem (1), was developed. Treatment of methyl (E)-4-methoxycinnamate 3 with chiral dioxirane, generated from chiral ketone 4, provided (-)-2 in 77% ee and 89% yield. The crude mixture of (-)-2 and 4 was efficiently separated by the use of novel and simple equipment performing a lipase-catalyzed transesterification and a continuous dissolution and crystallization to furnish the optically pure (-)-2 and recovery of 4 in 74% and 91% yield, respectively.",10.1021/jo025647b,2002-05-21,0.6010672618710884
Journal of Organic Chemistry,Synthetic Studies on Nogarol Anthracyclines. Enantioselective Total Synthesis of an Aminohydroxy Epoxybenzoxocin,"A chiral synthesis of the aminohydroxy expoxybenzoxocin 6 is described. Enantioselective Friedel-Crafts coupling using a chiral titanium catalyst was employed to produce the optically active atrolactic ester 16a from the phenol 11 and l-menthyl pyruvate (12). The phenolic group in 16a was protected as the benzyl ether and the t-alcohol functionality as the MEM ether to give 20, which after sequential reduction/oxidation provided the aldehyde 22. Addition of the acetylide anion of propargyl aldehyde diethyl acetal (23) to aldehyde 22, followed by oxidation of the resultant diastereoisomeric carbinols, gave the acetylenic ketone 24. Lindlar reduction of 24 afforded the trans-enone 26. Reaction of 26 with thiophenylate anion furnished 27, which was then cyclized to the alpha-methyl pyranoside 29. Oxidation of 29 to the sulfoxide and subsequent thermolysis afforded the hexenulose 30. Sequential epoxidation of 30, reduction of the keto epoxide 31, and reaction of the resultant epoxycarbinol 32 with dimethylamine produced the aminohydroxy pyranose 33a. Debenzylation of 33a to the phenol 33b, followed by intramolecular cyclization, completed the fabrication of the optically active aminohydroxy epoxybenzoxocin 6. The 17-step sequence from the phenol 11 to 6 was achieved in 22% overall yield.",10.1021/jo991483w,2000-03-01,0.6010634018058282
Angewandte Chemie International Edition,Conformation‐Enabled Total Syntheses of Ohmyungsamycins A and B and Structural Revision of Ohmyungsamycin B,"The first total syntheses of the bioactive cyclodepsipeptides ohmyungsamycin A and B are described. Key features of our synthesis include the concise preparation of a linear cyclization precursor that consists of N-methyl amides and non-proteinogenic amino acids, and its macrolactamization from a bent conformation. The proposed structure of ohmyungsamycin B was revised based on its synthesis. The cyclic core of the ohmyungsamycins was shown to be responsible for the excellent antituberculosis activity, and ohmyungsamycin variants with truncated chains were evaluated for their biological activity.",10.1002/anie.201711286,2018-01-30,0.6010549849172122
Organic Letters,"Synthesis of 1,2,3-Triazolo-Fused Allocolchicine Analogs via Intramolecular Oxidative Biaryl Coupling","A novel series of 1,2,3-triazolo-fused allocolchicine analogs is described. The strategy to prepare these analogs involves two steps: The first step is the synthesis of 1,2,3-triazole derivatives using our previously reported triazolization method, and in the second step, cyclization between two aromatic rings occurs by using the combination of PIFA and BF 3 ·Et 2 O as an oxidative coupling reagent. Furthermore, the diversity of aromatic rings and functional groups is explored in order to obtain seven- and eight-membered ring systems with medicinal chemistry interest.",10.1021/acs.orglett.9b01707,2019-06-26,0.6010410775442994
Angewandte Chemie International Edition,Total Synthesis of (+)-Concanamycin F,"The choice of protecting groups proved imperative for successful macrocyclization in the total synthesis of the 18-membered macrolide concanamycin F (1), which is a potent inhibitor of vacuolar (H+) ATPases. A C14 – C22 subunit was prepared with complete stereocontrol by using asymmetric, boron-mediated, aldol reactions with appropriate chiral ketones. Other key steps included a copper(I)-mediated, Liebeskind cross-coupling and a Mukaiyama aldol reaction for subunit assembly.",10.1002/(sici)1521-3773(20000403)39:7<1308::aid-anie1308>3.0.co;2-7,2000-04-03,0.601039805520432
Synlett,A Synthesis of Taxanes by Lactam-sulfoxide Ring Contraction and Intramolecular Pinacol Coupling,"All articles of this category A synthesis of the taxane ring system is described. The A-ring moiety 5 , containing the carbons for construction of the B-ring, was prepared from Wieland-Miescher ketone via Beckmann fragmentation of the oxime 10 . The B-ring was formed by means of 12-membered lactam-sulfoxide ring contraction. The formation of the C-ring was carried out by aldol condensation of the resulting AB-ring moiety 3 followed by intramolecular pinacol coupling to give the tricyclic diol 23 . taxane - ring contraction - SmI 2 - pinacol coupling - Beckmann fragmentation",10.1055/s-1999-3101,1999-12-31,0.6010385899780649
Journal of Organic Chemistry,Synthesis of an Adenine Nucleoside Containing the (8′<i>R</i>) Epimeric Carbohydrate Core of Amipurimycin and Its Biological Study,"The (8'R) epimeric carbohydrate core 2 of amipurimycin was synthesized from D-glucose derived allylic alcohol 3 in 11 steps and 13% overall yield. The key steps involve an acid-catalyzed acetonide ring opening of 9 with concomitant formation of an unprecedented pyranose ring skeleton to give 2,7-dioxabicyclo[3.2.1]octane 10. The α-orientation of the furan ring in 10 readily allows the stereoselective β-glycosylation and opening of the furanose ring that on removal of protecting groups affords the pyranosyl adenine nucleoside 2. The antifungal and anticancer activities of 2 were studied.",10.1021/jo102193q,2011-03-07,0.6010305054399369
European Journal of Organic Chemistry,"Enantioselective Synthesis of the Unsymmetrical Bis(lactone) (−)-(3E,6R,9E,12S,14R)-Colletol Induced by Chiral Sulfoxides and an Approach to (+)-Colletodiol by Asymmetric Hydroxylation of an α,β-Hydroxy Lactone","A general synthetic strategy towards the two bis(lactones) (−)-colletol (1) and (+)-colletodiol (2) is described. A common intermediate in this synthesis is the 6-membered hydroxy lactone (+)-(3R,5R)-3-hydroxy-5-hexanolide (6), readily prepared by stereoselective reduction of (+)-(SR)-methyl 3,5-dioxo-6-(p-toluenesulfinyl)hexanoate (7). Stereoselective hydroxylation of this hydroxy lactone has allowed efficient access to (+)-colletodiol (2).",10.1002/(sici)1099-0690(200001)2000:2<357::aid-ejoc357>3.0.co;2-n,2000-01-01,0.6010302276859607
Tetrahedron,A new and efficient asymmetric synthesis of oseltamivir phosphate (Tamiflu) from d-mannose,,10.1016/j.tetlet.2012.08.143,2012-09-07,0.6010245832109924
Tetrahedron,Synthetic approaches toward mitomycins. I. Stereoselective synthesis of a tetracyclic intermediate.,,10.1016/s0040-4039(00)87791-6,1986-01-01,0.6010172809686692
Tetrahedron,Synthetic approaches toward naphthyridinomycin. I. Stereoselective synthesis of a tetracyclic intermediate.,,10.1016/s0040-4039(00)85425-8,1986-01-01,0.6010172809686692
Tetrahedron,"“4,7-lactams”, intermediates for penems synthesis. II. Total synthesis of (+)-2,2-dimethyl-9-oxo-3-oxa-6-thia-1-azabicyclo [5.2.01,7]nonane",,10.1016/s0040-4039(01)82089-x,1981-01-01,0.6010168288183734
Journal of Organic Chemistry,Synthesis of Rebeccamycin and 11-Dechlororebeccamycin,"Glycosylated 7-chloroindole-3-acetamide 9, prepared in four steps and 26% yield from 7-chloroindole (1), was condensed with methyl 7-chloroindole-3-glyoxylate 11 and methyl indole-3-glyoxylate 12 to provide bisindolylmaleimides 7 and 8 in 86% and 84% yield, respectively. Oxidation of 7 and 8 followed by debenzylation provided a new approach to the synthesis of rebeccamycin and completed for the first time a synthesis of 11-dechlororebeccamycin.",10.1021/jo982277b,1999-03-05,0.6010130273660835
Angewandte Chemie International Edition,Total Synthesis of Cruentaren A,A triple bypass: The triple bond in the macrolactone ring of 2 served as a lock to prevent the unwanted translactonization to the δ-lactone during the formation of the side chain of the macrolide cruentaren A (1). Subsequent cleavage of the methyl ether and the silicon protecting groups (PG) followed by a Lindlar reduction of the two triple bonds completed the synthesis (see scheme).,10.1002/anie.200701423,2007-05-27,0.6010114212545858
Tetrahedron,A highly stereocontrolled asymmetric total synthesis of epimer of (+)-7-deoxypancratistatin,,10.1016/j.tetlet.2013.07.125,2013-07-31,0.6010100682680322
Journal of the American Chemical Society,Synthesis of Indoles via 6π-Electrocyclic Ring Closures of Trienecarbamates,"A new method for the preparation of indoles from readily available alpha-haloenones and alpha-(trialkylstannyl)enecarbamates is described. Following a Stille coupling, trienecarbamate 2 is electronically activated to undergo a facile 6pi-electrocyclic ring closure and subsequent oxidation to afford protected aniline 4. Upon deprotection and reductive amination, acid 5 underwent clean cyclization to N-acetylindole 6 (Ac2O, NEt3, 130 degrees C). This method has been used to construct a variety of substituted indoles that are not easily prepared by conventional indole annelation methods.",10.1021/ja060282o,2006-03-30,0.6010086390423471
Synthesis,Stereocontrolled Synthesis of<i>C</i>-Arylglycosides Applied to the South West Fragment of the Antibiotic Kendomycin,A nine step synthesis of the southwest fragment 3 of the antibiotic kendomycin (1) is reported. The tetrahydropyran ring is prepared in a highly stereocontrolled and efficient sequence. The key step concerns an anti-aldol reaction using chiral ketone 10. C-Aryl glycoside 3 exhibits atropisomerism and the relative configuration around its tetrahydropyran ring was established by NOE experiments.,10.1055/s-2002-35990,2002-01-01,0.6010083697602624
Tetrahedron,Two-step synthesis of the bipyrrole precursor of prodigiosins,,10.1016/j.tetlet.2006.02.035,2006-02-24,0.6010079102158116
European Journal of Organic Chemistry,"Asymmetric Synthesis of 2‐Mono‐ and 2,3‐<i>trans</i>‐Disubstituted Azetidines","Abstract A versatile and efficient asymmetric synthesis of 2‐mono‐ and 2,3‐ trans ‐disubstituted azetidines with excellent diastereomeric ( de = 93 to ⩾ 96%) and enantiomeric excesses ( ee ⩾ 96%) in good overall yields is described. Virtually stereoisomerically pure differently N , O ‐protected 3‐amino‐1‐alkanols were prepared as intermediates. Key steps are a diastereoselective α‐alkylation of aldehyde SAMP‐hydrazones with benzyloxymethyl chloride as the electrophile, and a nucleophilic 1,2‐addition of various organocerium reagents to the hydrazone CN double bond. An epimerisation‐free reductive removal of the auxiliary gave O ‐benzyl‐protected 3‐amino‐1‐alkanols. After N ‐tosylation and hydrogenolytic cleavage of the benzylic protecting group, ring closure to the corresponding N ‐tosylazetidines was achieved in good yields under Mitsunobu conditions. Detosylation was easily accomplished employing sodium/naphthalene. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2004)",10.1002/ejoc.200400473,2004-10-13,0.6010066504569835
Angewandte Chemie International Edition,Total Synthesis of the Antimitotic Marine Macrolide (−)‐Leiodermatolide,"Leiodermatolide is an antimitotic macrolide isolated from the marine sponge Leiodermatium sp. whose potentially novel tubulin-targeting mechanism of action makes it an exciting lead for anticancer drug discovery. In pursuit of a sustainable supply, we report a highly stereocontrolled total synthesis (3.2% yield) based on a convergent sequence of palladium-mediated fragment assembly and macrolactonization. Boron-mediated aldol reactions were used to configure the three key fragments 2, 5, and 6 by employing the appropriate enantiomer of the lactate-derived ketone 7.",10.1002/anie.201310164,2014-01-30,0.6010049701243894
Tetrahedron,Synthesis of 5-cyclodecenones via RCM and a three-pot sequence for bisannulation,,10.1016/j.tetlet.2016.07.084,2016-07-30,0.60100354639429
Synthesis,Synthesis of a Conformationally Rigid Analogue of 2-Aminoadipic Acid Containing an 8-Azabicyclo[3.2.1]octane Skeleton,"A new, conformationally rigid analogue of 2-amino­adipic acid, 8-[(benzyloxy)carbonyl]-3-methylene-8-azabicyclo[3.2.1]octane-1,5-dicarboxylic acid, is synthesized from dimethyl rac-2,5-dibromohexanedioate. The key steps involve alkylation-cyclization of 1-benzyl 2,5-dimethyl pyrrolidine-1,2,5-tricarboxylate with 3-chloro-2-(chloromethyl)prop-1-ene to yield the 8-azabicyclo[3.2.1]octane skeleton.",10.1055/s-0029-1216963,2009-08-21,0.6009971829590017
Organic Letters,Concise and Highly Stereoselective Synthesis of the C20–C26 Building Block of Halichondrins and Eribulin,"A concise, stereoselective, and scalable synthesis of the C20-C26 building block of halichondrins and Eribulin is reported. The synthesis relies on three key transformations: regiospecific Ru-catalyzed intramolecular hydrosilylation, highly stereoselective S(N)2' substitution, and selective conversion of a C-Si to C-I bond. It is carried out in a 5-pot/4-workup operation without chromatographic purification, except for filtration through a silica-gel plug, to give the C20-C26 building block (dr > 200:1; ee > 99%) in ca. 60% overall yield from epoxide 1.",10.1021/ol203373d,2012-01-11,0.6009921097011182
Organic Letters,Synthetic Efforts toward the C22−C36 Subunit of Halichondrin B Utilizing Local and Imposed Symmetry,"The C22-C34 portion (2) of halichondrin B was synthesized from meso-symmetric bis-silyl protected cyclopentenediol (7) in 20 steps and 7% overall yield. This was accomplished through a two-directional synthesis/terminus differentiation strategy that proceeded via achiral, meso-symmetric intermediates for eight steps and employed a Pd(0)-mediated asymmetric double cycloetherification to establish both tetrahydropyran rings. [Structure: see text]",10.1021/ol0473400,2005-01-21,0.6009919940416686
European Journal of Organic Chemistry,Total Synthesis of (±)‐Pumiliotoxin C: An Electrochemical Approach,"Abstract The total stereoselective synthesis of the decahydroquinoline alkaloid (±)‐pumiliotoxin C ( cis‐ 195A , 1 ) is described. The compound was prepared in 15 steps from the commercially available 4‐piperidone ethylene ketal 2 , in an overall 5 % yield. New C–C bonds in the α position relative to the nitrogen atom were formed by the metalation of aminonitriles 4 and 15 , which were themselves prepared electrochemically. The ease of this synthesis shows that the N ‐aryl group is an efficient nitrogen‐protecting group that can be removed in the last step through a Birch dearomatization. In addition, the aryl substituent serves as an efficient activator of the nitrogen atom during the elaboration of aminonitriles 4 and 15 . The oxygen atom of the keto carbonyl group in octahydroquinolinone 10 was removed by an unprecedented two‐step method involving a Shapiro reaction and a palladium‐catalyzed reduction of the intermediate alkene 13 . Finally, the expected stereospecific alkylation–hydride reduction process of the cis ‐fused aminonitrile 15 established the trans relationship between the propyl group at C‐2 and the methyl substituent at C‐5. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2005)",10.1002/ejoc.200400846,2005-05-25,0.6009747867296925
Journal of Organic Chemistry,Synthesis of Modified Carboxyl Binding Pockets of Vancomycin and Teicoplanin,"Sixteen-membered macrocycle 3 and 16+14 bicyclic compound 4, incorporating a terminal primary hydroxyl group in the peptide sequence, have been designed and synthesized. The syntheses feature the use of an efficient cycloetherification based on an intramolecular S N Ar reaction for the formation of biaryl ether bonds. Cyclization of linear tetrapeptide 30, prepared via a convergent [2+2] segment coupling between 26 and 29, gave macrocycle 31 (P configuration) as a single isolable atropisomer. Removal of the Boc protecting group afforded the modified carboxyl binding pocket of vancomycin 3 . A sequential 2-fold intramolecular S N Ar reaction has been used to construct the model bicyclic system (i.e. 4 ) of the D -O- E - F -O- G ring of teicoplanin. Cyclization conditions (CsF, DMF, room temperature) are sufficiently mild that the configuration of the racemization-prone arylglycine residue was not affected. Chiral building blocks such as d -(1 R )-[2-[( tert -butyldimethylsilyl)oxy]-1-[3-(allyloxy)phenyl]ethyl]amine 16, and l -( S )- N -Boc-[3-(isopropyloxy)phenyl]glycine ( 32 ) were synthesized employing Evans' asymmetric azidation method, while l -( S )-4-fluoro-3-nitrophenylalanine methyl ester 23 was prepared using Schöllkopf's bislactim ether as chiral glycine template. Compound 3 showed interesting conformational properties compared to vancomycin and its binding with Ac- d -Ala was studied by NMR titration experiments. A dissociation constant ( K d = 5 × 10 - 4 ) was calculated by a curve fitting method. Compound 4 is currently the most advanced synthetic intermediate toward the total synthesis of teicoplanin.",10.1021/jo961412m,1996-01-01,0.6009734481264669
Journal of the American Chemical Society,"Total Synthesis of Lucilactaene, A Cell Cycle Inhibitor Active in p53-Inactive Cells","Hetero-bis-metalated 1,3-butadiene is employed in the lynchpin coupling of synthetic fragments of the side chain of the antitumor agent, lucilactaene. Sequential Stille and Suzuki-Miyaura couplings interpolate this unique boron/tin diene into the pentaene chain. The total synthesis of lucilactaene was accomplished efficiently, in just eight linear steps.",10.1021/ja056217g,2005-10-27,0.6009668392266968
Synlett,Indium Trichloride Catalyzed One-Pot Synthesis of New (2-Amino-3-cyano-4H-chromen-4-yl) Phosphonic Acid Diethyl Ester,A one-pot synthesis of new (2-amino-3-cyano-4H-chromen-4-yl) phosphonic acid diethyl ester was achieved in good yields by indium trichloride catalyzed three-component reaction of salicylaldehyde and malononitrile with triethyl phosphite.,10.1055/s-0028-1087960,2009-03-16,0.6009646430522183
Synthesis,"Preparation of 4-Hydroxy-2-trifluoromethylthiophene: A Novel Bioisostere of α,α,α-Trifluoro-m-cresol","All articles of this category A simple and convenient four-step synthesis of 4-hydroxy-2-trifluoromethylthiophene ( 1 ) a novel bioisostere of α , α , α -trifluoro- m -cresol is reported. The key step is the condensation between ethyl 3-methoxy-4,4,4-trifluorocrotonate and methyl thioglycolate to form methyl 3-hydroxy-5-trifluoromethylthiophene-2-carboxylate ( 6 ). Hydrolysis of the ester followed by decarboxylation furnishes 1 . Multi-hundred gram quantities of 1 have been obtained utilizing the present procedure. addition-reactions - cyclizations - thiophenes - Fiesselmann reaction - bioisosteres",10.1055/s-2000-6320,2000-01-01,0.6009602636634178
Synthesis,Convergent Synthesis of Angiotensin II Receptor Blockers through C–H Arylation of 1-Benzyl-5-phenyl-1H-tetrazole with Functionalized Aryl Bromides,"Abstract Highly convergent synthesis of angiotensin II receptor blockers has been accomplished by means of late-stage C–H arylation using functionalized aryl bromides. C–H arylation of 1-benzyl-5-phenyl-1H-tetrazole with aryl bromides carrying methyl 2-ethoxybenzimidazole-7-carboxylate unexpectedly provided coupling products where ethyl group was migrated from oxygen to nitrogen atom. The O-to-N ethyl migration was completely suppressed by the use of N-pivaloyl-l-valine rather than the combined use of triphenylphosphine and sodium mesitylenesulfonate to result in the preferential formation of a key intermediate of candesartan cilexetil. In contrast, when an aryl bromide having ethyl 4-(1-hydroxy-1-methylethyl)-2-propylimidazole-5-carboxylate was employed, the C–H arylation proceeded smoothly to provide a late-stage intermediate, which rapidly led to olmesartan medoxomil in 3 steps.",10.1055/a-1472-0925,2021-03-31,0.600960249611807
Organic Letters,Efficient Synthesis of β-CF<sub>3</sub>/SCF<sub>3</sub>-Substituted Carbonyls via Copper-Catalyzed Electrophilic Ring-Opening Cross-Coupling of Cyclopropanols,"The first copper-catalyzed ring-opening electrophilic trifluoromethylation and trifluoromethylthiolation of cyclopropanols to form Csp3-CF3 and Csp3-SCF3 bonds have been realized. These transformations are efficient for the synthesis of β-CF3- and β-SCF3-substituted carbonyl compounds that are otherwise challenging to access. The reaction conditions are mild and tolerate a wide range of functional groups. Application to a concise synthesis of LY2409021, a glucagon receptor antagonist that is used in clinical trials for type 2 diabetes mellitus, is reported as well.",10.1021/acs.orglett.5b00782,2015-04-17,0.6009600859050507
Tetrahedron,Synthesis of α- alkoxysilanes: Birch reduction of 2-trialkylsilylfurans,,10.1016/s0040-4039(96)02101-6,1996-12-01,0.6009473143672129
Tetrahedron,Reduction of α-halogenated imines synthesis of pyrroles and aziridines,,10.1016/s0040-4039(01)91851-9,1974-01-01,0.6009473143672129
Tetrahedron,"The synthesis, reduction and cyclisation of N-(3-butynyl)- morpholin-and-thiomorpholin-2,6-diones",,10.1016/s0040-4039(00)81335-0,1983-01-01,0.6009473143672129
Organic Letters,A Convergent Total Synthesis of Ustiloxin D via an Unprecedented Copper-Catalyzed Ethynyl Aziridine Ring-Opening by Phenol Derivatives,[reaction: see text] The ustiloxins are a family of heterodetic cyclopeptides that have been isolated from the water extracts of false smut balls on the panicles of rice plants caused by the fungus Ustilaginoidea virens. A concise total synthesis of ustiloxin D has been achieved via an unprecedented ethynyl aziridine ring-opening of phenol derivatives. The longest linear sequence of the synthesis is 15 steps from commercially available compounds.,10.1021/ol052287g,2005-10-12,0.600946733753186
Tetrahedron,A novel synthesis of 3-aminoazetidines by ring transformation of 2-(bromomethyl)aziridines,,10.1016/s0040-4039(00)01844-x,2000-12-01,0.6009453477434139
Journal of Organic Chemistry,"Synthetic Approaches to Indolo[6,7-<i>a</i>]pyrrolo[3,4-<i>c</i>]carbazoles:  Potent Cyclin D1/CDK4 Inhibitors","Synthesis of indolo[6,7-a]pyrrolo[3,4-c]carbazoles 1, a new class of cyclin D1/CDK4 inhibitors, by oxidation of the corresponding aryl indolylmaleimides 2, will be described. Two approaches to the synthesis of 2 were identified that required new methods for the synthesis of 7-substituted indole acetamides 3 and N-methyl (indol-7-yl)oxoacetates 6. The chemistry developed enabled introduction of functionality (-OR, NR(2)) at C(12) and N(13) facilitating structure-activity relationship (SAR) evaluation of this indolocarbazole platform.",10.1021/jo035606v,2004-03-31,0.6009451102842945
Journal of the American Chemical Society,A Divergent Synthesis of Numerous Pyrroloiminoquinone Alkaloids Identifies Promising Antiprotozoal Agents,"High Resolution Image Download MS PowerPoint Slide On the basis of a streamlined route to the pyrroloiminoquinone (PIQ) core, we made 16 natural products spread across four classes of biosynthetically related alkaloid natural products, and multiple structural analogs, all in ≤8 steps longest linear sequence (LLS). The strategy features a Larock indole synthesis as the key operation in a five-step synthesis of a key methoxy-PIQ intermediate. Critically, this compound was readily diverged via selective methylation of either (or both) of the imine-like or pyrrole nitrogens, which then permitted further divergence by either O- demethylation to o- quinone natural products or displacement of the methoxy group with a range of amine nucleophiles. Based on a single, early report of their potential utility against the malaria parasite, we assayed these compounds against several strains of Plasmodium falciparum, as well as two species of the related protozoan parasite Babesia . In combination with evaluations of their human cytotoxicity, we identified several compounds with potent (low-nM IC 50 ) antimalarial and antibabesial activities that are much less toxic toward mammalian cells and are therefore promising lead compounds for antiprotozoal drug discovery.",10.1021/jacs.4c11897,2024-10-16,0.6009408605575067
Tetrahedron,An expedient and efficient synthetic route to some naturally occurring polyfunctional naphthazarins,,10.1016/s0040-4039(01)01940-2,2001-12-01,0.600939865362171
Tetrahedron,2-Methyl N-(p-toluenesulfinyl)aziridine-2-carboxylic acid: Asymmetric synthesis of α-methylphenylalanine and α-methyl-β-phenylserine,,10.1016/0040-4039(96)01168-9,1996-07-01,0.6009380141547569
Journal of Organic Chemistry,Enantioselective Synthesis of (<i>S</i>)- and (<i>R</i>)-Tolterodine by Asymmetric Hydrogenation of a Coumarin Derivative Obtained by a Heck Reaction,"An efficient and short enantioselective synthesis of (S)- and (R)-tolterodine was performed by asymmetric hydrogenation of a coumarin intermediate, easily obtained by a Heck reaction from inexpensive and commercially available starting materials.",10.1021/jo0705667,2007-07-11,0.600937105771015
Synlett,A Novel Synthesis of Hemispherands,"All articles of this category A novel, flexible synthesis of hemispherands {2,5,8-trioxa[9](3,3″) m -terphenylophanes 5a-d } with different central aromatic groups is described. The key step comprises the introduction of the central aromatic ring in the last step of the synthesis via a Suzuki cross-coupling reaction using palladium tetrakis(triplienylphosphine) as a catalyst and sodium or potassium cations serving as a template ion in the macrocyclization.",10.1055/s-1992-22013,1992-01-01,0.6009327542903622
Synlett,A Direct Entry to Carbasugars: Asymmetric Synthesis of 1-<i>epi</i>-(+)-MK7607,A short and flexible synthesis of 5a-carbasugars is presented. The combination of a proline-catalyzed aldol reaction and a ring-closing metathesis affords 1-epi-(+)-MK7607 in seven steps with an overall yield of 23%.,10.1055/s-2006-956495,2006-12-01,0.6009283097291117
Reaction Chemistry & Engineering,Rapid route design of AZD7594,Multidisciplinary collaboration enables the rapid and efficient design and selection of an improved manufacturing route to a new potential medicine for the treatment of asthma.,10.1039/c9re00118b,2019-01-01,0.6009281855671743
Organic Letters,Modular Total Synthesis of Protein Kinase C Activator (−)-Indolactam V,"A concise, eight-step total synthesis of (-)-indolactam V, a nanomolar agonist of protein kinase C, is reported. The synthesis relies upon an efficient copper-catalyzed amino acid arylation to establish the indole C4-nitrogen bond. This cross-coupling method is applicable to a range of hydrophobic amino acids, providing a platform for further diversification of indolactam alkaloid scaffolds and studies on their potent biological activity.",10.1021/acs.orglett.6b00614,2016-04-13,0.6009225168723192
Organic Process Research & Development,Practical Large-Scale Synthesis of Doripenem:  A Novel 1β-Methylcarbapenem Antibiotic,"A practical large-scale process for the synthesis of doripenem hydrate ( 1 ), a novel parenteral 1β-methylcarbapenem antibiotic, from p -nitrobenzyl-protected enolphosphate 2b and N -( p -nitrobenzyloxycarbonyl)-protected aminomethylpyrrolidine 3c is described. We found effective extraction conditions to remove p -toluidine and most other organic impurities using a THF/water system containing an inorganic salt. Significant improvements have been made to the previous synthesis using a medicinal chemical procedure. The new process requires no chromatographic purification and affords the target compound 1 as a sterile crystalline powder. Several kilograms of compound 1 were successfully prepared by this process.",10.1021/op034088n,2003-09-24,0.6009183815894859
Organic Process Research & Development,Process Development of ONO-2506:  A Therapeutic Agent for Stroke and Alzheimer's Disease,"A process for the synthesis of ONO-2506, an agent that suppresses astrocyte activation, has been developed. Significant improvement of the level of impurities in the final product has been achieved compared with the laboratory-scale procedure. Kilogram quantities of the compound have been supplied for preclinical studies by this improved process, with both a high quality (99.8%) and a high optical purity (99.6% ee). This was achieved by formation of a crystalline salt of an intermediate which could be recrystallized to give high purity. Toward the future launch of this product, residual problems such as byproduct formation during stereoselective allylation and removal of chiral auxiliary steps were also solved by further investigation.",10.1021/op034008f,2003-02-11,0.6009166422404013
Journal of Organic Chemistry,Rigid Dipeptide Surrogates:  Syntheses of Enantiopure Quinolizidinone and Pyrroloazepinone Amino Acids from a Common Diaminodicarboxylate Precursor,"A versatile and practical approach for synthesizing azabicyclo[X.Y.0]alkane amino acids of different ring sizes from a common diaminodicarboxylate precursor has been developed as a means for mimicking different peptide conformations. (2S,9S)-1-tert-Butyl 10-benzyl 5-oxo-2-[N-(PhF)amino] 9-[N-(BOC)amino]dec-4-enedioate (18) was first prepared in 83% yield by the Horner-Wadsworth-Emmons olefination of N-(PhF)aspartate beta-aldehyde 8 with pyroglutamate-derived beta-keto phosphonate 12 (PhF = 9-phenylfluoren-9-yl). The practicality of this approach for making azabicyclo[X.Y.0]alkane amino acids was then illustrated by the first synthesis of enantiopure quinolizidin-2-one amino acid 6 in seven steps and 40% overall yield from L-pyroglutamic acid. Hydrogenation of delta-keto alpha,omega-diaminosebacate 18, followed by lactam cyclization and protection, gave quinolizidin-2-one amino acid 6 as a single diastereomer. The versatility of this approach was next demonstrated by the synthesis of both ring-fusion isomers of pyrroloazepin-2-one amino acid 6 in 11 steps and 13% overall yield from pyroglutamic acid. Hydride reduction of 18, followed by methanesulfonate displacement, gave 5-alkylproline 22. Protective group manipulations, lactam cyclization, and removal of the ester group afforded readily separable pyrroloazepinone amino acids (7S)- and (7R)-7 in a 1:2 diastereomeric ratio. By introducing two new azabicycloalkane amino acids using our olefination approach, we have expanded the diversity of these important heterocycles for studying the conformational requirements for peptide biological activity.",10.1021/jo991766o,2000-03-16,0.6009164596594443
Synlett,Stereocontrolled Synthesis of ABC Tricycle of Solanoeclepin A,"A tricyclic compound possessing oxabicyclo[2.2.1]heptane and seven-membered ring of solanoeclepin A, the most active hatching agent of potato cyst nematode, was synthesized from d -pantolactone. The synthesis features a tin-mediated 6- exo -trig radical cyclization followed by iodoetherification and ring-closing enyne metathesis.",10.1055/s-0034-1380399,2015-03-03,0.6009160102599674
Organic Letters,Total Synthesis of (−)-Lepistine,"The first total synthesis of (-)-lepistine has been accomplished in 11 steps from (S)-glycidol. The synthesis features construction of the 10-membered ring via an intramolecular epoxide opening by nosylamide, regioselective dehydration to form an enol ether, and construction of the aminal moiety induced by cleavage of the nosyl groups.",10.1021/ol5010033,2014-05-09,0.6009083012892994
Synthesis,"Synthese von (+)- und (-)-Homononactinsäure. Totalsynthese des Makrotetrolids Tetranactin durch ""Reverse Coupe du Roi "". Strukturvorschlag für Isodinactin","All articles of this category The syntheses of (-)- and (+)-homononactic acid were achieved in 4 steps and 6 steps, respectively, starting with the reaction of 2-lithio-5-vinylfuran and ( S )-(-)-ethyloxirane. The vinyl group was transformed to the branched aldehyde by a regiospecific oxo reaction. Oxidation to the carboxylic acid, esterification, and hydrogenation of the furan ring formed four diastereomers of methyl homononactate. Two of these isomers were used directly for the synthesis of tetranactin, the others could be recycled by epimerisation and separation. The achiral macrolide antibiotic was constructed from two molecules of chiral (+)-homononactyl-(-)-homononactic acid by ester formation via the acid chloride and subsequent lactonisation via the (active) thiocarboxylic S -(3-cyano-4,6-dimethyl-2-pyridinyl) ester. The structure of isodinactin was corrected by comparing the optical rotations of methyl nonactate and methyl homononactate from natural origin with those of the optically pure synthetic compounds.",10.1055/s-1986-31846,1986-01-01,0.6009007491437454
Organic Letters,Total Synthesis of (−)-Gardmultimine A,"The first total synthesis of Gardneria oxindole alkaloid (−)-gardmultimine A has been achieved in 19 steps from d -tryptophan in a fully stereocontrolled manner. This synthesis features (1) an Ir-catalyzed regioselective C–H borylation/oxidation sequence to introduce the C12 methoxyl group, (2) a stereocontrolled oxidative rearrangement of indole to construct the spirooxindole motif, and (3) an Au(I)-catalyzed transannular Conia-ene-type 6-exo-dig cyclization to establish the azabicyclo[2.2.2]octane skeleton and the exocyclic E -alkene with exclusive stereoselectivity.",10.1021/acs.orglett.0c00399,2020-02-25,0.6009002098065471
Synthesis,"Stereoselective Total Synthesis of (-)-Aspinolide B from (<i>R</i>)-2,3-<b><i>O</i></b>-Isopropylideneglyceraldehyde","Key words (R)-2,3-O-isopropylideneglyceraldehyde - Jacobsen hydrolytic kinetic resolution - Sharpless asymmetric epoxidation - 1,2-anti selective reduction - Yamaguchi lactonization",10.1055/s-2007-990824,2007-11-26,0.6008981260678853
Organic Letters,Modular Construction of Dendritic Carbosilanes. Organization of Dendrimer Connectivity around Bifunctional Precursors That Are Adapted for Sequential Convergent and Divergent Propagative Steps,"Regiospecific hydrosilylation of 1-bromo-4-(prop-2-enyl)benzene offers an efficient route to molecular building block precursors that can accommodate sequential divergent and convergent steps for dendritic extension, establishing a modular methodology for assembly and organization of connectivity used for synthesis of modified carbosilane dendrimers including 14.",10.1021/ol000038g,2000-05-11,0.6008963734672852
Journal of the American Chemical Society,"A Concise, Stereocontrolled Total Synthesis of Rippertenol","The first total synthesis of the unique terpene rippertenol, a molecule with dense stereochemical complexity arrayed on a compact framework largely devoid of functional groups, is described. Key elements include orchestrated and unique applications of aldol condensations, Diels-Alder chemistry, and a ring expansion to advance a chiral starting material containing a single chiral center into the final target in a concise and diastereocontrolled manner.",10.1021/ja202859f,2011-05-17,0.6008896947697431
Tetrahedron,"Synthesis of (2S,3S,8S,9S)-Adda from D-glucose","The N-trifluoroacetyl derivative of the novel β-amino acid (2S,3S,8S,9S)-Adda methyl ester 4 has been prepared from the D-glucose derived oxazoline 7. A key step in the construction of 4 was the generation of the E,E decadienoate system via dissolving metal reduction of vicinal bis-mesylate 15.",10.1016/0040-4039(96)01217-8,1996-08-01,0.600880874621066
Tetrahedron,Two unusual isoflavonoids from Campylotropis hirtella – A new biosynthesis route of flavonoids,,10.1016/j.tetlet.2017.02.080,2017-03-02,0.6008732863048738
Synlett,Synthesis of a Potent Pan-Serotype Dengue Virus Inhibitor Having a Tetrahydrothienopyridine Core,"A synthesis of the first-in-class pan-serotype dengue virus inhibitor NITD-688 is presented. The Gewald reaction of N-(tert-butoxycarbonyl)-6,6-dimethylpiperidin-3-one with malononitrile and sulfur in the presence of l-proline as a catalyst gave tert-butyl 2-amino-3-cyano-6,6-dimethyl-6,7-dihydrothieno[3,2-c]pyridine-5(4H)-carboxylate. This was coupled with [4-(aminosulfonyl)phenyl]acetic acid by using propane­phosphonic acid anhydride. A subsequent reductive alkylation with cyclohexanecarboxaldehyde gave NITD-688. Preliminary results of our attempts to control the regioselectivity of the Gewald synthesis of the 2-amino-3-cyanothiophene core are also presented.",10.1055/a-1323-4036,2020-11-26,0.6008721901119595
Journal of Organic Chemistry,"Total Synthesis of (+)-Papuamine:  An Antifungal Pentacyclic Alkaloid from a Marine Sponge, <i>Haliclona </i>sp.","The total synthesis of (+)-papuamine, the antipode of the C(2)-symmetric, optically active, pentacyclic diamine natural product, starting from a chiral diol is described. The diol is available via an asymmetric Diels-Alder reaction between 1,3-butadiene and di-(-)-menthyl fumarate. The key transformation in the synthesis is an intramolecular Pd(0)-catalyzed (Stille) coupling reaction to form the central 13-membered diazadiene macrocyclic ring.",10.1021/jo951413z,1996-01-01,0.6008676567061554
European Journal of Organic Chemistry,Towards a Total Synthesis of Phenalinolactone Core Diterpenoid 6: Synthesis of a Racemic Decahydrobenzocyclobutaisobenzofuran with a <i>trans‐anti‐cis</i> Junction of the Isocyclic Rings,"Synthetic efforts towards the “phenalinolactone core diterpenoid 6” ( 5 ) are described. It contains a cyclohexyl alcohol (A ring), a cyclohexane (B ring), and a cyclohexene (C ring), which are angularly annulated trans and cis , respectively. What makes them unique is the trans ‐ (or “ anti ”‐) relationship between the A and the C ring. The trans ‐configured A/B ring junction was established in a novel cyclohexanone annulation. Anti ‐selective cis ‐annulations of the C ring failed when attempted with intramolecular Diels–Alder reactions with dienes of varied electron demand ( 21 , 31 ). In contrast, an anti ‐selective cis ‐annulation of a C ring precursor based on an intramolecular [2+2]‐photocycloaddition succeeded. It provided the tetracycle 38 in 70 % yield. It contains a densely functionalized four‐membered ring. It should lend itself to ring‐opening(s) and/or rearrangement(s). Accordingly, compound 38 should be adoptable to proceeding to the target structure 5 in future work.",10.1002/ejoc.201700198,2017-03-02,0.6008664771453157
Tetrahedron,Enantiospecific total synthesis of a novel arachidonic acid metabolite 3-hydroxyeicosatetraenoic acid,,10.1016/s0040-4039(97)10565-2,1998-01-01,0.6008661701070758
Tetrahedron,The first total synthesis of (±)-4-methoxydecanoic acid: a novel antifungal fatty acid,,10.1016/j.tetlet.2009.07.074,2009-07-19,0.6008661701070758
European Journal of Organic Chemistry,Reductive Amination Routes in the Synthesis of Piperidine IminoSugars,"The reductive amination (RA) reaction plays a pivotal role in the synthesis of new C–N bonds, due to the availability of many different and low‐cost reagents and their operational simplicity. The introduction in a compound of a nitrogen‐containing moiety that can be reduced to an amine in the reaction medium allows to perform cascade reactions which further expand this method. The application of the intramolecular version of the RA to carbohydrates allows the synthesis of polyhydroxypiperidine iminosugars, which are among the most challenging and fascinating glycomimetics for a synthetic chemist. This minireview focuses on the use of RA and of the double reductive amination (DRA) reaction in the key ring‐closing step en route to the synthesis of these compounds.",10.1002/ejoc.201901840,2020-02-27,0.6008543474755562
Journal of the American Chemical Society,Synthesis of the Death-Cap Mushroom Toxin α-Amanitin,"α-Amanitin is an extremely toxic bicyclic octapeptide isolated from the death-cap mushroom, Amanita phalloides. As a potent inhibitor of RNA polymerase II, α-amanitin is toxic to eukaryotic cells. Recent interest in α-amanitin arises from its promise as a payload for antibody-drug conjugates. For over 60 years, A. phalloides has been the only source of α-amanitin. Here we report a synthesis of α-amanitin, which surmounts the key challenges for installing the 6-hydroxy-tryptathionine sulfoxide bridge, enantioselective synthesis of (2 S,3 R,4 R)-4,5-dihydroxy-isoleucine, and diastereoselective sulfoxidation.",10.1021/jacs.7b12698,2018-03-21,0.6008499632563203
Organic Letters,The Rapid and Facile Synthesis of Oxyamine Linkers for the Preparation of Hydrolytically Stable Glycoconjugates,"The synthesis of a number of N-glycosyl-N-alkyl-methoxyamine bifunctional linkers is described. The linkers contain an N-methoxyamine functional group for conjugation to carbohydrates and a terminal group, such as an amine, azide, thiol, or carboxylic acid, for conjugation to the probe of choice. The strategy for the linker synthesis is rapid (3-4 steps) and efficient (51-96% overall yield), and many of the linkers can be synthesized using a three-step one-pot strategy. Moreover, the linkers can be conjugated to glycans in excellent yield and they show excellent stability toward hydrolytic cleavage.",10.1021/ol503634j,2015-01-16,0.6008486549409345
Journal of the American Chemical Society,Total Synthesis of (−)-Enigmazole A,"A highly convergent, stereocontrolled total synthesis of the architecturally complex marine sponge metabolite (-)-enigmazole A has been achieved. Highlights include an unprecedented late-stage large-fragment Petasis-Ferrier union/rearrangement, a multicomponent Type I Anion Relay Chemistry (ARC) tactic, and a dithiane-epoxide union in conjunction with an oxazole-directed stereoselective reduction.",10.1021/jacs.5b11540,2015-12-03,0.6008380858000594
Journal of Organic Chemistry,Total Synthesis of Caloporoside,"The first total synthesis of the fungal metabolite caloporoside 1, a strong and selective inhibitor of phospholipase C, is described. Both sugar units of its complex disaccharidic segment were obtained from 3,4,6-tri- O -benzyl- d -glucopyranose 14 as a common building block, with d -gluco → d -manno inversions as the key strategic elements. This particular substitution reaction occurred readily on the acyclic segment ( 27 → 28 ), whereas ultrasonication was required to override adverse stereoelectronic effects upon formation of β- d -mannopyranoside unit 34 . The (16 R )-hydroxyheptadecylsalicylic acid part of 1 was efficiently prepared by a palladium-catalyzed Suzuki cross coupling reaction of aryltriflate 7 with the 9-alkyl-9-BBN derivative formed from alkene 6 and 9-H-9-BBN.",10.1021/jo9800098,1998-04-16,0.6008303231301964
Tetrahedron,"Synthesis of B-ring functionalised intermediates for the preparation of 1,9-dideoxy-forskolin derivatives",,10.1016/s0040-4039(01)01321-1,2001-10-01,0.600814697025598
Tetrahedron,A new strategy for the synthesis of chromans and chromenes,,10.1016/s0040-4039(98)00937-x,1998-07-01,0.6008097451992752
Tetrahedron,A new strategy for the synthesis of the pheromones of Lobesia botrana and Bombyx mori,,10.1016/s0040-4039(00)80057-x,1988-01-01,0.6008097451992752
Synthesis,A Selective and Efficient Synthesis of (<i>E</i>)-4-Methyl-3-alken-1-ols via Zirconium-Catalyzed Carboalumination of Terminal Alkynes,,10.1055/s-1980-29313,1980-01-01,0.6008071448792073
Synthesis,Regioselective FeCl3-Promoted Biomimetic Synthesis of Dimeric Isorhapontigenin,"An efficient approach to the preparation of natural (+/-)-gneafricanin F and the first synthesis of (+/-)-gnemonol M were developed. The regioselective, oxidative coupling of 5-tert-butyl-isorhapontigenin catalyzed by FeCl3 center dot 6H(2)O in different solvent systems was used as the key synthetic step.",10.1055/s-0030-1258242,2010-09-03,0.6008042954589694
Angewandte Chemie International Edition,Selective Formation of Imines by Aerobic Photocatalytic Oxidation of Amines on TiO<sub>2</sub>,An oxygenation pathway: The title transformation involves a two-step process: a selective oxygenation step to generate aldehyde intermediates and a subsequent condensation step to afford the imine products (see scheme).,10.1002/anie.201007056,2011-03-04,0.6007931586919338
Tetrahedron,"Lipase-catalyzed transesterification as a practical route to homochiral syn-1,2-diols. The synthesis of the taxol side chain",,10.1016/s0040-4039(98)00147-6,1998-04-01,0.6007787720134047
European Journal of Organic Chemistry,"Total Synthesis of Bauhinoxepin J: A Biologically Active Dibenzo[<i>b</i>,<i>f</i>]oxepin Isolated from <i>Bauhinia purpurea</i>","Abstract Bauhinoxepin J possessing antimycobacterial, antimalarial, and tumor growth inhibitory activities was efficiently synthesized. The method involves crucial steps, including a coupling reaction of two aromatic moieties to construct the desired carbon framework, chemoselective phenol oxidation of a bisphenol derivative to establish a key cyclization precursor, and construction of a characteristic seven‐membered dihydrooxepin ring by internal cyclization to yield the target bauhinoxepin J.",10.1002/ejoc.201100845,2011-08-05,0.6007784691535344
Tetrahedron,"Furanyl spiroketals as stereochemical relays in the synthesis of 1,9-anti diols: synthesis of insect pheromones",,10.1016/j.tetlet.2007.06.004,2007-06-11,0.600777932275484
Organic Process Research & Development,"An Efficient Large-Scale Synthesis of EDP-420, a First-in-Class Bridged Bicyclic Macrolide (BBM) Antibiotic Drug Candidate","A multistep, practical, and cost-effective synthesis of novel bridged bicyclic macrolide drug candidate EDP-420 ( 1 ) is described. Starting from inexpensive and commercially available erythromycin A 9-oxime, the current chemical process involves a series of transformations: triacetylation, Pd-catalyzed O,O -bis-allylation (bridge formation), acid-catalyzed sugar cleavage, oxime reduction, acetylation, Os-catalyzed bridge olefin oxidative cleavage, Corey−Kim oxidation, bridge oxime formation, deprotection, and final purification. Multikilogram quantities have been synthesized.",10.1021/op900228u,2010-05-03,0.6007755117610126
Journal of Organic Chemistry,Total Synthesis and Biological Evaluation of Hybrubin A,"Here, we report the first total synthesis of hybrubin A, a bipyrrole tetramic acid alkaloid representing a new carbon framework derived from convergent (truncated red cluster and exogenous hbn cluster) biosynthetic pathways. A highly convergent synthesis was developed, employing 4-methoxy-1,5-dihydro-2 H -pyrrol-2-one ( 13 ) as a single starting material to provide hybrubin A in three steps from 13 and 20.8% overall yield. As no biological activity was prescribed to hybrubin A except for a lack of cytotoxicity, we further profiled this unique alkaloid across panels of discrete molecular targets. Interestingly, hybrubin A was found to be a ligand for a variety of GPCRs with a propensity for potent binding across therapeutically relevant adenosine receptors (A 1, A 2a, and A 3 ) as well as a potent activity at a kinase, FLT3. This pattern of biological activity is distinct from other related prodigiosin natural and unnatural products and is even more intriguing in the absence of cytotoxicity.",10.1021/acs.joc.6b02534,2016-12-05,0.6007642055451967
Synlett,Convergent Synthesis of theA-J Ring System of Yessotoxin,"A highly convergent synthesis of the A-J ring system of yessotoxin was achieved. A convergent strategy via α-cyano ethers was extensively applied in the assembly of the F and IJ ring fragments to afford the FGHIJ ring unit, followed by coupling with the ABC ring unit.",10.1055/s-2008-1078266,2008-08-21,0.6007440604398386
Journal of the American Chemical Society,"Synthesis, Molecular Editing, and Biological Assessment of the Potent Cytotoxin Leiodermatolide","It was by way of total synthesis that the issues concerning the stereostructure of leiodermatolide (1) have recently been solved; with the target now being unambiguously defined, the mission of synthesis changes as to secure a meaningful supply of this exceedingly scarce natural product derived from a deep-sea sponge. To this end, a scalable route of 19 steps (longest linear sequence) has been developed, which features a catalytic asymmetric propargylation of a highly enolizable β-keto-lactone, a ring closing alkyne metathesis and a modified Stille coupling as the key transformations. Deliberate digression from this robust blueprint brought a first set of analogues into reach, which allowed the lead qualities of 1 to be assessed. The acquired biodata show that 1 is a potent cytotoxin in human tumor cell proliferation assays, distinguished by GI50 values in the ≤3 nM range even for cell lines expressing the Pgp efflux transporter. Studies with human U2OS cells revealed that 1 causes mitotic arrest, micronucleus induction, centrosome amplification and tubulin disruption, even though no evidence for direct tubulin binding has been found in cell-free assays; moreover, the compound does not seem to act through kinase inhibition. Indirect evidence points at centrosome declustering as a possible mechanism of action, which provides a potentially rewarding outlook in that centrosome declustering agents hold promise of being inherently selective for malignant over healthy human tissue.",10.1021/ja508846g,2014-10-27,0.600741434351408
Organic Letters,Synthesis of a Benzomacrolactone-Based Somatostatin Mimetic,The benzomacrolactone is a framework found in numerous natural products. The synthesis of an orthogonally functionalized benzomacrolactone from D-glucosamine and a salicylic acid derivative is described. This macrolactone was used for the synthesis of a somatostatin mimetic that has submicromolar affinity for the human somatostatin receptor 4 (hSSTR4).,10.1021/ol202528k,2011-10-11,0.6007409720803847
European Journal of Organic Chemistry,"A Short, Gram‐Scale Synthesis of 2,5‐Disubstituted Furans","Abstract A modified Feist–Bénary furan synthesis has been developed that involves a lithium aldol reaction between a methyl ketone and an α‐chloroaldehyde followed by a thermally induced tetrahydrofuran formation/dehydration sequence and affords 2,5‐disubstituted furans in good overall yield. This process is demonstrated on multigram scale and is amenable to the production of symmetric or asymmetric furans that incorporate a range of substituents (e.g., aryl, tert ‐butyl, ferrocenyl).",10.1002/ejoc.201300305,2013-04-25,0.6007352972207743
Angewandte Chemie International Edition,Ring-Opened Fullerenes: An Unprecedented Class of Ligands for Supramolecular Chemistry,"A window of opportunity: With the formation of a large orifice in the C60 core (1) and the successful insertion of He and H2 , two critical steps have been realized towards the development of an efficient synthetic approach for the preparation of endohedral fullerene complexes.",10.1002/1521-3773(20010817)40:16<2973::aid-anie2973>3.0.co;2-1,2001-08-17,0.6007277886779329
Synthesis,Skeletal Rearrangement of Pyridine Derivatives via a Light-Induced Ring Expansion,"Abstract We report an efficient synthetic route to access 1,2-diazepines from readily available pyridines through dearomative ring expansion. By initially using previously established methods to obtain the pyridinium ylide intermediate on multigram scale, the diazepine was obtained through a 6π electrocyclic ring opening upon irradiation with 370 nm light. 1,2-Diazepines are among the least common nitrogen heterocycles present in FDA-approved drugs, likely due to the lack of synthetic pathways that enable access to these scaffolds rather than a lack of biological significance. While pyridine expansions are generally multistep procedures, our work has shown promise for a one-pot route to this expansion product. Taken together, this work provides access to synthetically difficult drug cores, while also introducing synthetic handles for further derivatization.",10.1055/a-2617-8749,2025-08-18,0.6007275980824842
Angewandte Chemie International Edition,"Total Syntheses of Sesterterpenoid Ansellones A and B, and Phorbadione","Abstract Ansellane‐type sesterterpenoids including, ansellones A‐G and (+)‐phorbadione are structurally novel marine secondary metabolites which exhibit anticancer and anti‐HIV activity. The first, asymmetric total syntheses of three structurally representative members, (−)‐ansellones A and B and (+)‐phorbadione, were accomplished in 16–23 steps from (+)‐sclareolide. The route features the first regioselective cyclization of vinyl epoxides with internal alcohol nucleophiles in a 1,4‐addition manner (S N 2′). Additionally, the allylic C−H oxidation was exploited at a late stage of the synthesis of (−)‐ansellone A and (+)‐phorbadione. This strategy is expected to be applicable to the synthesis of other ansellane sesterterpenoids.",10.1002/anie.201701879,2017-03-28,0.6007026399626046
Organic Letters,Regioselective Cyclization of (Indol-3-yl)pentyn-3-ols as an Approach to (Tetrahydro)carbazoles,"An acid-catalyzed, highly regioselective cycloisomerization as well as dehydro-cyclization of (indol-3-yl)pentyn-3-ols has been reported for the selective synthesis of tetrahydrocarbazoles and carbazoles. This process is mild and found to be very general in terms of structural diversity of substrates. Utilizing the strategy, an efficient synthetic approach for the functionalized frameworks of carbazomycins A-D has also been developed.",10.1021/acs.orglett.8b00042,2018-01-30,0.6006996872242951
Organic Letters,Asymmetric Total Synthesis of C9′- <i>epi</i> -Sinefungin,"-methionine, inhibits various SAM-dependent methyltransferases (MTs). Access to sinefungin analogues could serve as the basis for the rational design of small molecule methyltransferase inhibitors. We developed a route to the unnatural C9' epimer of sinefungin that employed a diastereoselective Overman rearrangement to install the key C6' amino stereocenter. The ability for late-stage modification is highlighted, opening an avenue for the discovery of new MT inhibitors.",10.1021/acs.orglett.0c01956,2020-07-06,0.6006890727343819
Tetrahedron,The synthesis of the C-9 to C-21 sector of discodermolide: An efficient route to the C13–14 Z-trisubstituted alkene,,10.1016/s0040-4039(00)77155-3,1994-04-01,0.6006883678865182
Tetrahedron,New enantioselective approach to the total synthesis of (−)-α-Kainic Acid,,10.1016/s0040-4039(98)00166-x,1998-04-01,0.6006777347637497
Synthesis,An Improved Synthesis of Methyl Triacetic Lactone Using Thallium(I) Salt of<i>t</i>-Butyl Acetoacetate,,10.1055/s-1975-23723,1975-01-01,0.6006749858170407
Organic Letters,Stereoselective Synthesis of Pyrrolidines from <i>N</i>-Allyl Oxazolidines via Hydrozirconation−Cyclization,[reaction: see text] A new diastereoselective synthesis of pyrrolidines from readily available chiral N-allyl oxazolidines is presented. The construction of the pyrrolidine ring is achieved via a tandem hydrozirconation-stereoselective Lewis acid mediated cyclization sequence.,10.1021/ol0517776,2005-10-01,0.600672926036914
Synthesis,"An Efficient Synthesis of 4-Oxo-2,5-hexadienoates via Δ<sup>2</sup>-Isoxazoline Intermediates","All articles of this category An efficient method for the preparation of 4-oxo-2,5-hexadienoates starting from 3,5-disubstituted Δ 2 -isoxazolines is described. The N-O bond cleavage of the isoxazoline ring, promoted by molybdenum hexacarbonyl, afforded the β-hydroxy ketone intermediates 9a-d which were smoothly dehydrated to the expected 4-oxo-2,5-hexadienoates 10a-d in about 40% yield starting from 6a,b .",10.1055/s-1993-26023,1993-01-01,0.6006674207660632
Organic Letters,"Unraveling the C<sub>2</sub>-Symmetric Azatetraquinane System. Simple, Enantioselective Syntheses","Concise stereocontrolled synthetic routes to the C 2 -symmetric azatetraquinane 1 (or, also, the enantiomer) are described. The successful execution of the synthesis involved innovation in the methodology for [3+2] cycloaddition and stereochemical control.",10.1021/acs.orglett.1c00387,2021-03-01,0.6006653296451023
Tetrahedron,The generation and cyclisation of pyridinium radicals as a potential route to indolizidine alkaloids,,10.1016/s0040-4039(97)01178-7,1997-07-01,0.6006639351155099
Angewandte Chemie International Edition,Enantioselective Synthesis of the Complex Rocaglate (−)‐Silvestrol,The total synthesis of the natural product (−)-silvestrol (1) has been accomplished and features enantioselective [3+2] photocycloaddition of a substituted 3-hydroxyflavone and methyl cinnamate promoted by a chiral Brønsted acid. Initial biological studies indicate a 5–10-fold greater activity of silvestrol as an inhibitor of protein synthesis in HeLa cells than its 1′′′′ diastereomer.,10.1002/anie.200702707,2007-09-05,0.600663600974494
Organic Process Research & Development,Overcoming the Challenges of Making a Single Enantiomer N-1 Substituted Tetrazole Prodrug Using a Tin-Mediated Alkylation and Enzymatic Resolution,"The synthesis of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor 3 is described. This complex structure contains a tetrazole modified by a chiral hemiaminal carbonate prodrug. A regioselective tin-mediated alkylation was utilized to access the N-1 alkylated tetrazole isomer, and a highly selective enzymatic hydrolysis efficiently provided the desired prodrug enantiomer. A Suzuki–Miyaura coupling was employed for the final fragment union, which was challenging due to base sensitivity of the prodrug. This route was enabled and used to manufacture multikilogram quantities of API 3 in an efficient manner.",10.1021/acs.oprd.9b00104,2019-05-09,0.60065971861542
Journal of Organic Chemistry,Synthetic Studies on (−)-Lemonomycin: An Efficient Asymmetric Synthesis of Lemonomycinone Amide,"Asymmetric synthesis of lemonomycinone amide (2) was accomplished from readily accessible starting materials. Enantioselective alkylation of N-(diphenylmethylene)glycine tert-butyl ester (11) by 5-tert-butyldimethylsilyloxy-2,4-dimethoxy-3-methylbenzyl bromide (10) in the presence of Corey-Lygo's phase transfer catalyst [O-(9)-ally-N-(9'-anthracenylmethyl) cinchonidium bromide, 0.1 equiv] afforded, after chemoselective hydrolysis of the imine function (THF/H(2)O/AcOH), the substituted l-tert-butyl phenylalanate 13 in 85% yield. A Pictet-Spengler reaction of 14 with benzyloxyacetaldehyde (15) provided the 1,3-cis-disubstituted tetrahydroisoquinoline 16 in 85% yield as a single diastereomer. Coupling of hindered secondary amine 16 with amino acid 9 was accomplished under carefully controlled conditions to furnish the amide 22, which was in turn converted to hemiaminal 24. A hafnium triflate catalyzed conversion of hemiaminal to alpha-amino thioether followed by a silver tetrafluoroborate promoted intramolecular Mannich reaction of 26 afforded the tetracycle 27 in excellent overall yields. Debenzylation of 27 [Pd(OH)(2), H(2), MeOH, 0 degrees C], removal of N-Boc function (aqueous 3 N HCl, MeOH/H(2)O), and oxidation of hydroquinone to quinone [(NH(4))(2)Ce(NO(3))(6), H(2)O, rt] afforded the lemonomycinone amide 2 in 76% yield over three steps.",10.1021/jo8027449,2009-02-05,0.6006547787207462
Tetrahedron,"Oxidative dimerization of 2-(1,4-dithiafulven-6-yl)thiophenes: an alternative route towards extensively π-conjugated tetrathiafulvalene analogs",,10.1016/0040-4039(95)00409-6,1995-04-01,0.6006542636104256
Journal of the American Chemical Society,Enantioselective Total Synthesis of (+)-Salvileucalin B,An enantioselective total synthesis of the diterpenoid natural product (+)-salvileucalin B is reported. Key findings include a copper-catalyzed arene cyclopropanation reaction to provide the unusual norcaradiene core and a reversible retro-Claisen rearrangement of a highly functionalized norcaradiene intermediate.,10.1021/ja110192b,2010-12-21,0.6006539568454616
Organic Letters,Concise Entry to Chiral 5-(4-Hydroxybutyl)-2(5<i>H</i>)-furanone via HTIB-Mediated Novel Oxidative Fragmentation: Formal Total Synthesis of (+)-Dubiusamine A,"The concise synthesis of 5-(4-hydroxybutyl)-2(5H)furanone has been accomplished from 9-oxabicyclo[4.2.1]non-7-en-1-ol on the basis of HTIB [PhI(OH)OTs, a.k.a. Koser's reagent]-mediated novel oxidative fragmentation. Chiral (-)-(R)-5-(4-hydroxy-butyl)-2(5H)-furanone (>99% ee) was used for the formal total synthesis of (+)-dubiusamine A (1).",10.1021/ol4005239,2013-03-26,0.6006233911187653
Synthesis,"A Straightforward Approach to Protected (S)-Dolaphenine (Doe), the Unusual Amino Acid Component of Dolastatin 10","A short, four-step synthesis of Boc-protected (S)-dolaphenine is described, starting from protected phenylalanyl glycine. The key step is the cyclization of an endothiodipeptide to give a thiazolyl­ triflate, which can be subjected to a palladium-catalyzed reduction with formic acid.",10.1055/s-0031-1289594,2011-11-07,0.6006219466699044
Organic Letters,Amphidinolide B:  Asymmetric Synthesis of a C<sub>7</sub>−C<sub>20</sub> Synthon,[reaction: see text] An asymmetric synthesis of a C(7)-C(20) synthon of amphidinolide B is described. The synthesis entails the construction of C(7)-C(13) and C(14)-C(20) fragments and makes extensive use of catalytic asymmetric bond constructions to establish the requisite stereochemical relationships. Fragment coupling proceeds by Suzuki cross-coupling and installs the trisubstituted diene unit that is among amphidinolide B's defining structural features.,10.1021/ol051861l,2005-12-07,0.6006147847814216
Journal of Organic Chemistry,Synthetic Studies toward the Total Synthesis of Scabrolide A,"Herein, we report a concise route to the [5-5-6]-fused tricyclic core of scabrolide A and our efforts toward the construction of the fourth cycloheptane ring of the molecule via a 7- endo-trig radical cyclization. The tricyclic cyclohexenone core was assembled by a ring-closing metathesis (RCM) reaction followed by oxidation and concomitant isomerization of the double bond. These promising results have potential implications in the synthesis of similar tricyclic cores of many other congeners within this family of furanobutenolide-derived polycyclic cembranoids and norcembranoids.",10.1021/acs.joc.5c00298,2025-04-16,0.600611212644248
Journal of Organic Chemistry,Total Synthesis of (±)-Rhazinal Using Novel Palladium-Catalyzed Cyclizations,"A concise synthesis of (+/-)-rhazinal that hinges on novel oxidative Heck cyclizations and palladium-catalyzed direct couplings is described. An X-ray structure of N-MOM-rhazinal, which provides insight into the conformation of the strained 9-membered lactam ring, is described.",10.1021/jo801791j,2009-01-26,0.6005900035715066
Synlett,Synthesis of Functionalized Carbon-Sulfur [5]Helicene: Pd-Catalyzed Negishi Cross-Coupling Between the β-Positions of Thiophenes,Octyl- and bromo-substituted carbon-sulfur [5]helicene was prepared in several steps starting from either thiophene or 3-bromothiophene. Pd-catalyzed Negishi cross-coupling between the β-positions of thiophenes was one of the key steps in the synthesis.,10.1055/s-2003-43335,2004-01-01,0.6005893031624091
European Journal of Organic Chemistry,A Three‐Step Synthesis of 4<i>H</i>‐Cyclopenta[<i>def</i>]phenanthrene from Pyrene,"Abstract 4 H ‐Cyclopenta[ def ]phenanthrene (CPP) is a valuable building block in the production of photoactive polymers, which find use in a wide range of organic electronic applications. Of particular importance is their use in the development of blue‐colored, organic light‐emitting diodes (OLEDs), which remains a challenge in the field. Unfortunately, commercial sources and synthetic procedures known in the literature are unable to provide enough CPP for large scale implementation. Herein, we report on the development of a novel, gram‐scale synthesis of CPP in three steps, starting from pyrene. The key steps in our methodology are the ring contraction of pyrene‐4,5‐dione to oxoCPP in a single step, as well as the direct reduction of oxoCPP to CPP. Apart from the small number of synthetic steps, our methodology benefits from the use of relatively non‐hazardous reagents, together with optimized purification procedures, making CPP accessible in useful quantities.",10.1002/ejoc.202100190,2021-03-16,0.6005863204716203
Angewandte Chemie International Edition,Total Synthesis of Vancomycin Aglycon—Part 1: Synthesis of Amino Acids 4-7 and Construction of the AB-COD Ring Skeleton,"A triazene-based synthetic strategy for the construction of the complex biaryl ethers and a Suzuki coupling reaction were the key steps in the synthesis of precursor 1 of the aglycon of vancomycin, which already contains the complete skeleton of the target compound. The cleavage of the triazene unit from the D ring and the removal of the other protecting groups led to the aglycon of vancomycin. These strategies should be particularly valuable for the synthesis of other naturally occurring glycopeptide antibiotics and offer opportunities for the synthesis of combinatorial libraries of compounds of the vancomycin family for chemical biology studies.",10.1002/(sici)1521-3773(19981016)37:19<2708::aid-anie2708>3.0.co;2-e,1998-10-16,0.600585047239425
Angewandte Chemie International Edition,Total Synthesis of Vancomycin Aglycon—Part 1: Synthesis of Amino Acids 4–7 and Construction of the AB-COD Ring Skeleton,"A triazene-based synthetic strategy for the construction of the complex biaryl ethers and a Suzuki coupling reaction were the key steps in the synthesis of precursor 1 of the aglycon of vancomycin, which already contains the complete skeleton of the target compound. The cleavage of the triazene unit from the D ring and the removal of the other protecting groups led to the aglycon of vancomycin. These strategies should be particularly valuable for the synthesis of other naturally occurring glycopeptide antibiotics and offer opportunities for the synthesis of combinatorial libraries of compounds of the vancomycin family for chemical biology studies.",10.1002/(sici)1521-3773(19981016)37:19<2708::aid-anie2708>3.3.co;2-5,1998-10-16,0.600585047239425
Synthesis,"Enantioselective Synthesis ofProtoberberine Alkaloids via (-)-Sparteine-mediatedAsymmetric Condensation-Cyclisation of <i>o</i>-ToluamideAnions with 3,4-Dihydroisoquinolines","The first asymmetric synthesis of protoberberine alkaloids based upon the (-)-sparteine-mediated lateral metalation of o-toluamides and subsequent addition-cyclisation with 3,4-dihydroisoquinolines is described (up to 77% ee).",10.1055/s-2003-40886,2003-08-01,0.6005828403827298
Synlett,"Highly Stereoselective Total Synthesis of the Natural Leukotriene (-)-(5<i>S</i>,6<i>S</i>)-LTA<sub>4</sub>Methyl Ester and of Its η-7-10 (Tricarbonyl) Iron Complex","All articles of this category The optically active (ee 96 %) leukotriene (5 S ,6 S ,7 E ,9 E ,11 Z , 14 Z )-5,6-epoxy-7,9,11,14-icosatetraenoic acid (LTA 4 ) methyl ester (-)- 12 and the corresponding η-7-10 (tricarbonyl) iron complex (+)- 10 have been synthesized in 12 and 11 steps, respectively and in overall yields of 15 % and 18 % starting from tricarbonyl[methyl ( R )-2-5-η-penta-2,4-dienoate]-iron. The key steps involve Friedel-Crafts acylation of the trichloroethyl ester of the starting complex with methyl 5-(chloroformyl)pentanoate, stereoselective transformation into the α-chlorodienone complex (+)- 3a , followed by subsequent transformation of the trichloroethyl ester into an aldehyde. Wittig reaction with the known ( Z )-(3-nonenylidene)triphenylphosphorane afforded the optically pure (ee 99 %) (tricarbonyl) iron complex (+)- 9 , possessing the entire functionalized carbon skeleton of the LTA 4 methyl ester. This common intermediate was readily converted to the LTA 4 methyl ester (-)- 12 , or its Fe(CO) 3 complex (+)- 10 .",10.1055/s-1991-20913,1991-01-01,0.6005817772918487
European Journal of Organic Chemistry,A New Stereoselective Synthesis of (±)-Grandisol Based on the Remote Alkylation Protocol,"A new stereoselective synthesis of (±)-grandisol (1a) has been developed. The synthesis starts with a simple cyclobutyl derivative to which the methyl group and the 1,2-cis disposed side chains were appended through a remote alkylation protocol.",10.1002/1099-0690(200107)2001:14<2659::aid-ejoc2659>3.0.co;2-x,2001-07-01,0.6005669464958089
Tetrahedron,"A new route to 5,6-dihydropyridine-2(1H)-thiones",,10.1016/0040-4039(96)01051-9,1996-07-01,0.6005613270533905
Journal of Organic Chemistry,Stereoselective Formal Total Synthesis of (+)-Methynolide,"A highly stereoselective and convergent formal total synthesis of (+)-methynolide is described. The salient features of this synthesis have been the construction of the C1-C7 and C8-C11fragments via a desymmetrization approach, Sharpless asymmetric epoxidation of an allyl alcohol, respectively, and linkage of both the fragments by Nozaki-Hiyama-Kishi reaction.",10.1021/jo0704762,2007-06-29,0.6005600320949449
European Journal of Organic Chemistry,A Concise and Divergent Approach to Hydroxylated Piperidine Alkaloids and Azasugar Lactams,"Abstract The vinylogous Mannich reaction (VMR) between 2‐( tert ‐butyldimethylsilyloxy)furan (TBSOF) and ( R S )‐ t ‐BS‐imine 12a and the application of the VMR adduct butenolide 13a as a versatile chiral building block for the synthesis of hydroxylated piperidine alkaloids and azasugars were investigated. Firstly, both the anti diastereoselectivity and the chemical yield of the asymmetric VMR between TBSOF and ( R S )‐ t ‐BS‐imine 12a were improved by the use of Sm(OTf) 3 /H 2 O (1.5 equiv.) as the promoter. Similar diastereoselectivities were also obtained with Yb(OTf) 3 /H 2 O, Cu(OTf) 2 /H 2 O, Zn(OTf) 2 /H 2 O, or the Brønsted acids TfOH or MsOH as the promotors. Secondly, an efficient four‐step procedure for the elaboration of butenolide 13a into piperidine alkaloid (–)‐deoxoprosophylline ( 2 ) was established. Thirdly, by taking advantage of the olefin functionality in the butenolide 13a , polyhydroxylated δ‐lactams 23 and 21 , which are ready precursors of azasugars L ‐deoxyallonojirimycin ( ent ‐ 7 ) and L ‐3‐ epi ‐fagomine ( ent ‐ 6 ), were obtained in two and three steps, respectively, via dihydroxylated lactone 17 . The easily available synthetic intermediate 17 can also serve as a key intermediate for the synthesis of the glycosyl nucleoside amino acid cores of polyoxins and nikkomycins.",10.1002/ejoc.201201618,2013-02-20,0.6005530385682673
Tetrahedron,FeCl3-catalyzed tandem Prins and Friedel–Crafts cyclization: a highly diastereoselective route to polycyclic ring structures,,10.1016/j.tetlet.2014.05.092,2014-06-02,0.6005468539972101
Journal of the American Chemical Society,The sequence of a stepwise AdE reaction and intramolecular Pauson-Khand cycloaddition as an entry into the synthesis of polycyclic compounds,"A stepwise AdE acylmethoxylation across the double bond of dicobalt hexacarbonyl complexes (DCHCC) of conjugated enynes was elaborated as an efficient and general route for the synthesis of DCHCC of 1,6-enynes containing a combination of five- and six-membered-ring fragments. Depending on the structure of these adducts, the latter either were subjected to 1,2-carbnyl reduction followed by an intramolecular Pauson-Khand (IMPK) cyclization or were directly utilized as substrates for this process. A list of model polycyclic systems which were assembled using this approach includes [5.5.5] angularly fused compounds, [6.5.5] and [5.5.5] linearly fused tricyclics, and linearly and angularly fused [6.5.5.5] and [5.5.5.5] tetracyclic products. A novel convergent and general method for the synthesis of various cyclic compounds is suggested on the basis of the AdE-IMPK tandem sequence as the key steps for the assemblage of polycyclic frameworks. This option seems to be especially promising for the tetracyclic derivatives mentioned above, as in these cases only two operationally simple steps are required to convert read:'-/ available starting blocks into the target structures related to natural polyquinanes.",10.1021/ja00040a012,1992-07-01,0.6005389315611028
European Journal of Organic Chemistry,"Synthesis of (+)‐6,7‐Dimethoxy‐1,2,3,4‐tetrahydroisoquinoline‐1‐carboxylic Acid, a Diastereoselective Approach","Abstract The diastereoselective synthesis of (+)‐6,7‐dimethoxy‐1,2,3,4‐tetrahydroisoquinoline‐1‐carboxylic acid (90 % ee ) was accomplished by employing a combination of two synthetic methods, that is, the Petasis synthesis of amino acids and the Pomeranz–Fritsch–Bobbitt synthesis of tetrahydroisoquinoline derivatives. The stereochemical outcome of the synthesis was controlled by chiral aminoacetaldehyde acetals, which were used as the amine component of the Petasis step to yield the Pomeranz–Fritsch–Bobbitt substrate for the tetrahydroisoquinoline ring formation in one simple operation.",10.1002/ejoc.201403218,2014-11-27,0.6005316197686568
Synthesis,"Synthesis of (<i>S</i>,<i>R</i>,<i>R</i>,<i>R</i>)-α,α′-Iminobis(methylene)bis(6-fluoro-3<i>H</i>,4<i>H</i>-dihydro-2<i>H</i>-1-benzopyran-2-methanol)","The β1-adrenergic antagonist (S,R,R,R)-α,α′-iminobis(methylene)bis(6-fluoro-3H,4H-dihydro-2H-1-benzopyran-2-methanol) was synthesized from natural chiral pool starting materials through an efficient, convergent synthetic strategy. The cyclization mechanism of the key step was investigated using computer modeling and is discussed.",10.1055/s-2007-965993,2007-04-01,0.6005296455766229
Tetrahedron,"A short, efficient chiral synthesis of a novel cholinergic channel activator, ABT-418 [(S)-3-methyl-5-(1-methyl-2-pyrrolidinyl)isoxazole], from (S)-pyroglutamic acid",,10.1016/0040-4039(95)00340-i,1995-04-01,0.6005231439808848
Tetrahedron,Asymmetrical synthesis of fluorinated 2-(pyridin-2-yl) alkylamine from fluoromethyl sulfinyl imines and 2-alkylpyridines,,10.1016/j.tetlet.2015.10.005,2015-10-19,0.6005098102902382
Journal of Organic Chemistry,Synthesis of Stereoisomers of <i>Artemisia</i> and <i>Chrysanthemum</i> Bis(acetylenic) Enol Ether Spiroacetals,"An 11-step synthesis is described of two diastereomeric candidates for a bis(acetylenic) enol ether spiroacetal isolated from Chrysanthemum boreale. Key steps in the synthetic route include spiroacetal lactone alkylidenation and subseqent modified Cadiot-Chodkiewicz cross-coupling to install the bis(acetylenic) enol ether functionality. From NMR comparisons, neither of the candidates, whose structures were confirmed by single-crystal X-ray diffraction, correspond to the natural product, and a proposal for the correct structure is put forward.",10.1021/jo301810d,2012-10-31,0.6005082845251246
Organic Process Research & Development,Enzymatic Desymmetrization Route to Ethyl [3-(2-Amino-2-methylpropyl)phenyl]acetate,"An efficient process to ethyl [3-(2-amino-2-methylpropyl)phenyl]acetate 6 has been developed. Key steps include a novel enzymatic desymmetrization of diester 2 and a Ritter reaction between alcohol 4 and chloroacetonitrile, followed by chemoselective deprotection with thiourea.",10.1021/op200108k,2011-06-24,0.6005039938390057
Reaction Chemistry & Engineering,Flow synthesis of an α-amino boronic ester as a key precursor of bortezomib drug,"The flow synthesis of the optically active α-amino boronate precursor of the bortezomib drug is described, including a key diastereoselective Matteson rearrangement.",10.1039/d2re00099g,2022-01-01,0.6004918379415081
Journal of Organic Chemistry,5-<i>tert</i>-Butylproline,"Steric effects on the isomer equilibrium of amides N -terminal to proline can be explored with 5-alkylprolines having bulky 5-position substituents. Enantiopure 5- tert -butylprolines were thus synthesized from glutamic acid via an acylation/diastereoselective reductive amination sequence. Double deprotonation of γ-methyl N -(PhF)glutamate ( 2 ) with LiN(SiMe 3 ) 2 and C -acylation with pivaloyl chloride provided β-keto ester 3, which upon γ-ester hydrolysis and decarboxylation gave δ-oxo-α-[ N -(PhF)amino]heptanoic acid ( 4 ). Syntheses of (2 S,5 R )- and (2 R, 5 S )- N -(BOC)-5- tert -butylprolines ((2 S,5 R )- 1 and (2 R, 5 S )- 1 ) were accomplished by catalytic hydrogenation of their respective (2 S )- and (2 R )-methyl δ-oxo-α-[ N -(PhF)amino]heptanoates ((2 S )- 5a and (2 R )- 5a ) in methanol with di- tert -butyl dicarbonate followed by chromatography and ester hydrolysis with potassium trimethylsilanolate. The 5- tert -butylproline cis -diastereomers were proven to be of >99% enantiomeric purity after their conversion to diastereomeric α-methylbenzylamides 10 . Good diastereoselectivity in favor of the trans -diastereomer was observed when (2 S,5 S )-5- tert -butylproline was synthesized from (2 S )-δ-oxo-α-[ N -(PhF)amino]heptanoate ((2 S )- 4 ) by solvolysis of the PhF group in trifluoroacetic acid and subsequent reduction of 5- tert -butyl-Δ 5 -dehydroproline ( 11 ) with tetramethylammonium triacetoxyborohydride; however, imino acid 11 was shown to be configurationally labile and racemized under acidic conditions. 5- tert -Butyl-Δ 5 -dehydroproline N ‘-methylamide 15 was configurationally stable in acid, yet preliminary attempts to reduce 15 favored cis -diastereomer 16 . Alternatively, enantiopure trans -diastereomer, (2 R, 5 R )-methyl N -(BOC)-5- tert -butylprolinate ( 9 ) was prepared by epimerization of (2 S,5 R )- 9 . In summary, this synthetic methodology now provides access to all four enantiopure 5- tert -butylproline isomers from inexpensive l - and d -glutamate as chiral educts.",10.1021/jo9618738,1996-01-01,0.6004863167526697
Journal of the American Chemical Society,Total Synthesis of Piericidin A1 and B1 and Key Analogues,"Full details of the total synthesis of piericidin A1 and B1 and its extension to the preparation of a series of key analogues are described including ent-piericidin A1 (ent-1), 4'-deshydroxypiericidin A1 (58), 5'-desmethylpiericidin A1 (73), 4'-deshydroxy-5'-desmethylpiericidin A1 (75), and the corresponding analogues 51, 59, 76, and 77 bearing a simplified farnesyl side chain. The evaluation of these key analogues, along with those derived from their further functionalizations, permitted a scan of the key structural features providing new insights into the role of the substituents found in both the pyridyl core as well as the side chain. A strategic late stage heterobenzylic Stille cross-coupling reaction of the pyridyl core with the fully elaborated side chain permitted ready access to the analogues in which each half of the molecule could be systematically and divergently modified. The pyridyl cores were assembled enlisting inverse electron demand Diels-Alder reactions of N-sulfonyl-1-azabutadienes, while key elements of side chain syntheses include an anti selective asymmetric aldol to install the C9 and C10 relative and absolute stereochemistry (for natural and ent-1) and a modified Julia olefination for formation of the C5-C6 trans double bond with convergent assemblage of the side chains.",10.1021/ja0632862,2006-08-18,0.6004814218115628
Journal of Organic Chemistry,Total Synthesis of (−)-Virginiamycin M<sub>2</sub>: Application of Crotylsilanes Accessed by Enantioselective Rh(II) or Cu(I) Promoted Carbenoid Si–H Insertion,"A stereoselective synthesis of the antibiotic (-)-virginiamycin M(2) is detailed. A convergent strategy was utilized that proceeded in 10 steps (longest linear sequence) from enantioenriched silane (S)-15. This reagent, which was prepared via a Rh(II)- or Cu(I)-catalyzed carbenoid Si-H insertion, was used to introduce the desired olefin geometry and stereocenters of the C1-C5 propionate subunit. A modified Negishi cross-coupling or an efficient alkoxide-directed titanium-mediated alkyne-alkyne reductive coupling strategy was utilized to assemble the trisubstituted (E,E)-diene. An underutilized late-stage SmI(2)-mediated macrocyclization was employed to construct the 23-membered macrocycle scaffold of the natural product.",10.1021/jo202119p,2011-11-09,0.6004767087331633
Organic Process Research & Development,Kilogram-Scale Synthesis of a Highly Selective α<sub>1</sub>-Adrenoceptor Antagonist (DL-028A),"This work presents an improved eight-step process, leading to kilogram quantities of high-quality DL-028A, an antihypertensive agent. The improvements include reducing the levels of toxic reagents and the removal of dangerous processes and waste gas treatment. Moreover, specification and impurity profiles were determined.",10.1021/op0100807,2002-04-17,0.6004686565567151
Journal of Organic Chemistry,Stereoselective Synthesis and Structural Confirmation of the Specialized Pro-Resolving Mediator Resolvin E4,"Herein, we report the stereoselective and convergent synthesis of resolvin E4, a newly identified specialized pro-resolving mediator. This synthesis proves the absolute configuration and exact olefin geometry. Key elements of the successful strategy include a highly stereoselective MacMillan organocatalytic oxyamination, a Midland Alpine borane reduction, and the use of a 1,4-pentadiyne unit as a linchpin building block. The application of reaction telescoping in several of the synthetic transformations enabled the preparation of the resolvin E4 methyl ester in 10% yield over 10 steps (longest linear sequence). The physical property (UV-Vis and LC-MS/MS) data of synthetic resolvin E4 matched those obtained from biologically produced material.",10.1021/acs.joc.0c02913,2021-02-03,0.6004669886980306
Angewandte Chemie International Edition,Catalytic Asymmetric Total Synthesis of (+)‐Chamaecydin and (+)‐Isochamaecydin and their Stereoisomers,"terpene quinone methides and their non-natural stereoisomers, which feature the presence of an unprecedented spiro[4.4]nonane-containing 6-6-6-5-5-3 hexacyclic skeleton. Resting on a chiral phosphinamide-catalyzed enantioselective reduction of 2,2-disubstituted cyclohexane-1,3-dione, a concise route for the synthesis of enantioenriched 6-6 bicyclic fragment was developed. The 6-6 ring fragment and the five-membered ring fragment were unified via a metal-halogen exchange/intermolecular addition reaction. Subsequently, the central 6-5 bicyclic ring system was constructed through a Michael/aldol cascade. The successful establishment of these strategic transformations allowed for an efficient and rapid construction of spiroannulated 6-6-6-5-5 pentacarbocyclic core via a convergent manner. Finally, the total syntheses of naturally occurring (+)-chamaecydin and (+)-isochamaecydin and their corresponding 1',5'-stereoisomers have been achieved divergently by appropriately orchestrating the reaction sequence including isopropyl incorporation, oxidation state adjustment, and carbonyl group-directed regio- and stereoselective cyclopropanation at a late stage.",10.1002/anie.202423944,2025-01-09,0.6004656819305794
Organic Letters,<i>N</i>-Methoxy-<i>N</i>-acylnitrenium Ions:  Application to the Formal Synthesis of (−)-TAN1251A,"[structure: see text]. A formal synthesis of the muscarinic M(1) receptor antagonist (-)-TAN1251A (7) from L-tyrosine is described. Central to this venture has been the construction of the 1-azaspiro[4.5]decane skeleton present in the natural product by an N-methoxy-N-acylnitrenium ion-induced spirocyclization. The dienone generated in this transformation, 10, was converted to (-)-TAN1251A via tricycle 9, an intermediate in Kawahara's recent synthesis of racemic 7.",10.1021/ol015626o,2001-03-14,0.6004475985561155
Journal of the American Chemical Society,Stereochemical Determination of the Leupyrrins and Total Synthesis of Leupyrrin A<sub>1</sub>,"The stereochemical determination of the potent antifungal agents leupyrrin A1 and B1 and the total synthesis of leupyrrin A1 are reported. The relative and absolute configuration was determined by a combination of high field NMR studies, molecular modeling, and chemical derivatization. The expedient total synthesis involves a one-pot sequential Zr-mediated oxidative diyne-cyclization/regioselective opening sequence for preparation of the unique dihydrofuran ring, a highly stereoselective one-pot approach to the butyrolactone, a challenging sp(2)-sp(3) Suzuki coupling and a high-yielding Shiina macrolactonization.",10.1021/jacs.5b01894,2015-03-13,0.6004398702510717
Tetrahedron,Novel pathway for the synthesis of arylpropionamide-derived selective androgen receptor modulator (SARM) metabolites of andarine and ostarine,,10.1016/j.tetlet.2013.02.065,2013-02-27,0.6004380789120588
Synthesis,"A Modular Four-Component Route to Substituted 1,7,9-Decatrien-3-ones Using a Chloro-Substituted Phosphorane as Key C3 Building Block","An efficient and flexible four-component route to substituted 1,7,9-decatrien-3-ones was established by alkylation of sodium dialkyl malonates with a chloro-substituted phosphorane followed by a Wittig reaction with the corresponding carbonyl compound. The resulting enones were alkylated at their malonate unit with sorbyl bromide to give the title compounds in good overall yields. In an attempt to improve the overall yield by using in situ generated sorbyl tosylate we discovered the formation of an unusual bicyclic product with a 3-oxocyclopenta[ b ]furan core that is formally generated by an oxidative dimerization of the employed precursor enone. The structure of this compound was unambiguously determined by an X-ray crystal analysis.",10.1055/s-0035-1562724,2016-07-26,0.6004283949812503
Organic Letters,Pot-Economical Total Synthesis of Clinprost,"The pot-economical synthesis of clinprost is reported, in which the core bicyclo[3.3.0]octenone structure was synthesized by two key steps: an asymmetric domino Michael/Michael reaction catalyzed by diphenylprolinol silyl ether and an intramolecular Horner–Wadsworth–Emmons reaction. The trisubstituted endocyclic alkene was selectively introduced by 1,4-reduction followed by trapping of the generated enolate with Tf 2 NPh and subsequent utilization of the Suzuki–Miyaura coupling reaction. Chiral, nonracemic clinprost was synthesized in seven pots with a 17% total yield and excellent enantioselectivity.",10.1021/acs.orglett.0c03616,2020-11-24,0.6004262122828049
Organic Letters,Synthesis of the GPR40 Partial Agonist MK-8666 through a Kinetically Controlled Dynamic Enzymatic Ketone Reduction,"A scalable and efficient synthesis of the GPR40 agonist MK-8666 was developed from a simple pyridine building block. The key step to set the stereochemistry at two centers relied on an enzymatic dynamic kinetic reduction of an unactivated ketone. Directed evolution was leveraged to generate an optimized ketoreductase that provided the desired trans alcohol in >30:1 dr and >99% ee. Further, it was demonstrated that all four diastereomers of this hydroxy-ester could be prepared in high yield and selectivity. Subsequently, a challenging intramolecular displacement was carried out to form the cyclopropane ring system with perfect control of endo/exo selectivity. The endgame coupling strategy relied on a Pd-catalyzed C-O coupling to join the headpiece chloropyridine with the benzylic alcohol tailpiece.",10.1021/acs.orglett.6b02910,2016-11-01,0.6004209389478532
Organic Letters,"Enantioselective Desymmetrization of 3-Substituted Oxetanes: An Efficient Access to Chiral 3,4-Dihydro-2<i>H</i>-1,4-benzoxazines","Herein, we describe a versatile transition metal/oxidant free synthesis of the chiral 2 H -1,4-benzoxazines through chiral phosphoric acid (CPA) catalyzed enantioselective desymmetrization of prochiral oxetanes (30 examples) in up to 99% yield and 99% enantioselectivity under mild reaction conditions. The reported strategy not only complements the conventional 2 H -1,4-benzoxazine synthetic strategies but also provides access to key intermediates of therapeutic candidates, i.e., prostaglandin D2 receptor antagonist and M1 positive allosteric modulator (PAM) compound VU0486846.",10.1021/acs.orglett.1c03419,2021-11-24,0.6004193644618316
Journal of Organic Chemistry,"Synthesis of Phosphotriester Analogues of the Phosphoinositides PtdIns(4,5)P<sub>2</sub> and PtdIns(3,4,5)P<sub>3</sub>","A synthetic route was developed for the preparation of novel O -(3-aminopropyl) tethered phosphotriester analogs ( 5 ) of phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5,)P 2, or PIP 2 ) and phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P 3, or PIP 3 ) using the coupling reagent 2-cyanoethyl N, N, N ‘, N ‘-tetraisopropylphosphorodiamidite. The phosphotriester ligand design introduced a reactive aminopropyl group at the polar lipid head of the ring-phosphorylated phosphoinositides, allowing a reporter moiety to be positioned at the surface of the bilayer and in the vicinity of the phosphorylated inositol. Such reporter groups may interact with membrane-proximal regions of PIP 2 - and PIP 3 -binding proteins recruited to membrane sites by electrostatic interactions between the phosphates of the phospholipid and basic regions of the proteins. Following a convergent strategy, phosphitylation of an optically-pure 1,2- O -diacyl- sn -glycerol with 2-cyanoethyl N, N, N ‘, N ‘-tetraisopropylphosphorodiamidite was followed by coupling with protected inositol precursors to give adducts 8 in 80% to 95% yield. The 2-cyanoethyl phosphotriester was stable during the subsequent reaction steps and could be conveniently converted to the 3-aminopropyl group during the final hydrogenolysis of the benzyl protecting groups. Benzophenone-containing photoaffinity probes of the phosphotriester 11a and 11b were also synthesized. Alternatively, the versatile cyanoethyl group could be removed using diisopropylethylamine prior to hydrogenolysis, thereby furnishing the corresponding phosphodiesters, PIP 3 and PIP 2 ( 13a and 13b ).",10.1021/jo961226g,1996-01-01,0.6004192997625308
Journal of Organic Chemistry,"Stereoselective Syntheses of 1,4-Dideoxy-1,4-imino-octitols and Novel Tetrahydroxyindolizidines","A new route for the preparation of four new indolizidines, (1R,2S,6S,7S,8aS)- and (1R,2S,6R,7R,8aS)-1,2,6,7-tetrahydroxyindolizidine (30 and 32) and (1S,2R,7S,8S,8aR)- and (1S,2R,7R,8R,8aR)-1,2,7,8-tetrahydroxyindolizidine (44 and 46), is reported. The synthesis is based on Knoevenagel homologation of the readily available enantiomerically pure pyrrolidin-carbaldehydes 13 and 37followed by asymmetric dihydroxylation of the subsequent alkenyl pyrrolidines and cyclization of the corresponding imino-octitols. The new indolizidines and their precursors (imino-octitols 20, 25, 26) and indolizidinones 28a and 28b have been tested for inhibitory activities toward 26 glycosidases. The enzymatic inhibition of trans-7-hydroxy-d-(-)-swainsonine (44) toward alpha-mannosidases is similar to that described for trans-7-hydroxy-l-(+)-swainsonine (11b) toward naringinase (alpha-l-rhamnosidase from Penicillium decumbens).",10.1021/jo026688a,2003-04-24,0.6004192385703615
Journal of the American Chemical Society,Asymmetric Synthesis of Ageliferin,We describe herein an asymmetric synthesis of ageliferin. A Mn(III)-mediated oxidative radical cyclization reaction was used as the key step to construct the core skeleton of this pyrrole-imidazole dimer. This approach resembles the biogenic [4 + 2] dimerization in an intramolecular fashion.,10.1021/ja207386q,2011-09-04,0.6004069333278953
Angewandte Chemie International Edition,"Total Synthesis of Indotertine A and Drimentines A, F, and G","Oh my darling, Drimentine: The first total synthesis of the pyrroloindoline alkaloids drimentines A, F, and G, and their congener, indotertine A, is reported. An intermolecular radical conjugate addition was key in the synthesis of the drimentine alkaloids, and a biologically inspired iminium–olefin cyclization converted drimentine F into indotertine A.",10.1002/anie.201303334,2013-07-15,0.6003945552029291
Journal of Organic Chemistry,Total Synthesis of Gibbilimbols A−D,Gibbilimbols A-D (1-4) were synthesized in 32-49% yield over four steps from commercially available starting materials. A copper-catalyzed coupling of 4-methoxyphenylmagnesium bromide with various unsaturated alkyl bromides was the key step in assembling the (long-chain alkyl)phenol skeleton.,10.1021/jo0162991,2002-03-14,0.6003692156328487
Organic Letters,Synthetic Studies toward Plumisclerin A,"A concise approach to synthesize the tetracyclic framework of the marine diterpenoid plumisclerin A is described. Starting from commercially available iridoid genipin, a highly selective intermolecular Diels–Alder reaction was utilized to construct the A/B/C tricycle. Later, a four-step sequence involving stereoselective epoxidation and Dauben oxidative rearrangement was developed to introduce the requisite enone moiety. The unique tricyclo[4,3,1,0 1,5 ]decane motif was successfully forged via a late-stage SmI 2 -mediated reductive coupling.",10.1021/acs.orglett.9b00095,2019-02-15,0.6003623773959831
Organic Letters,"Asymmetric Syntheses of (2<i>R</i>,3<i>S</i>)-3-Hydroxyproline and (2<i>S</i>,3<i>S</i>)-3-Hydroxyproline","Two synthetic routes have been developed for the asymmetric syntheses of (2 R,3 S)- and (2 S,3 S)-3-hydroxyproline. The key synthetic step in each of these strategies is the conversion of protected α,δ-dihydroxy-β-amino esters (either 2,3- anti- or 2,3- syn-configured) into β,δ-dihydroxy-α-amino esters (protected forms thereof), via the intermediacy of the corresponding aziridinium ions. The products of these stereospecific rearrangements were then cyclized and deprotected to afford (2 R,3 S)-3-hydroxyproline and (2 S,3 S)-3-hydroxyproline as single diastereoisomers (>99:1 dr) in >26% overall yield.",10.1021/acs.orglett.8b01736,2018-06-26,0.6003606125765264
European Journal of Organic Chemistry,Synthesis and Biological Evaluation of Gephyronic Acid Derivatives: Initial Steps towards the Identification of the Biological Target of Polyketide Inhibitors of Eukaryotic Protein Synthesis,"Abstract Coupled to the development of a total synthesis of gephyronic acid, a series of diastereomeric analogues and their precursors have been prepared by employing complementary aldol strategies for the key coupling step of fragments 4 and 5 . A biological evaluation revealed the importance of the epoxide for the cytotoxicity against L‐929 (mouse fibroblast) and KB‐3‐1 (HeLa clone, human cervix carcinoma derived) cell lines. Moreover, variation of the configuration of the C3–C5 stereotriad and the C1 carboxylic acid were found to be important features. Improved activities compared with the natural product were observed when the carboxy terminus at C1 was replaced by a methyl ester or PMB‐protected alcohol. Surprisingly, the derivatives (8 R )‐ 17d and (8 S )‐ 16a showed antibacterial activity against Pseudomonas aeruginosa .",10.1002/ejoc.201101129,2011-10-28,0.600352285569605
Synthesis,"Syntheses of Pyrazine-, Quinoxaline-, and Imidazole-Fused Pyrroline Nitroxides","A synthesis of a new diamagnetic synthon, 1-methoxy-2,2,5,5-tetramethylpyrrolidine-3,4-dione, was developed. Condensation of this compound with aliphatic or aromatic 1,2-diamines followed by deprotection yielded pyrroline nitroxide-fused pyrazines, pteridines, or quinoxalines, demonstrated on 7 examples in 15–39% overall yield over 2 or 3 steps. Reaction of the diamagnetic 1,2-diketone with an aldehyde and ammonium acetate produced a pyrrolo[3,4-d]imidazole scaffold in the Debus–Radziszewski reaction.",10.1055/s-0039-1690678,2019-09-13,0.6003498870532468
Tetrahedron,A new and efficient domino strategy to indole derivatives synthesis and its C3-bisfunctionalization,,10.1016/j.tetlet.2012.09.120,2012-10-02,0.600347279131441
Journal of Organic Chemistry,Formal Total Synthesis of (±)-Estrone via the Furano Diene Approach,"We present in this report the development and realization of a novel formal total synthesis of estrone (1) via the Torgov diene (24) by the furano diene approach, first attempted by Woodward in 1937. The core ring structure 16 was established by an acid-mediated regioselective and stereospecific cyclization of the endo-oxabicyclo[2.2.1]heptene derivative 14, which is readily available from the AlCl(3)-catalyzed Diels-Alder cycloaddition of 2-(3-methoxyphenethyl)furan (4) and dimethyl maleate. The mechanistic pathway of this S(N)' type cyclization is discussed, and the earlier perspectives in our preliminary report (Org. Lett. 2004, 6, 1333) are corrected.",10.1021/jo1015486,2010-12-06,0.6003464357103507
Synlett,"An Expedient Route to the Quinolone Antibacterial Intermediate, 2,4,5-Trifluorobenzoic Acid","(opens in new window) Buy Article (opens in new window) Permissions and Reprints (opens in new window) All articles of this category (opens in new window) A short and efficient synthesis of the important quinolone antibacterial intermediate, 2,4,5-trifluorobenzoic acid ( 1 ), is reported. 3,4, 6-Trichlorophthalic acid is protected as an N -methyl- or N -phenylphthalimide and then fluorinated. Acid hydrolysis then gives 3,4, 6-trifluorophthalic acid which is selectively decarboxylated to give 1 in high yield.",10.1055/s-1990-21183,1990-01-01,0.6003434588676119
Angewandte Chemie International Edition,"Convergent Total Syntheses of Callipeltosides A, B, and C","Going for the hat-trick: The synthesis of the entire callipeltoside family of natural products is described. Key to this synthesis was the coupling of the di-ene-yne and pyran fragments by a diastereoselective alkenylzinc addition allowing rapid access to the common aglycon. Attachment of each relevant L-configured sugar resulted in the first total synthesis of callipeltoside B (see scheme), and the syntheses of callipeltosides A and C.",10.1002/anie.201204868,2012-08-22,0.600341872371916
Tetrahedron,A novel two-step method to prepare new unsymmetrical cryptands,,10.1016/s0040-4039(00)61220-0,1992-08-01,0.6003360628647858
Organic Letters,Total Synthesis of the Immunosuppressant FR901483 via an Amidoacrolein Cycloaddition,"[reaction: see text]. The total synthesis of the potent immunosuppressant FR901483 is described. In a key step, the intermolecular Diels-Alder cycloaddition of an amidoacrolein with 2-(triisopropylsilyloxy)-1,3-butadiene produced the desired 3-cyclohexene-1-carboxaldehyde. This compound was subjected to basic followed by acidic conditions which effected two sequential aldol cyclizations to deliver the tricyclic ring system of the natural product, suitably functionalized for completion of the total synthesis.",10.1021/ol015506g,2001-03-23,0.6003356612492542
Organic Letters,Chemoselective and Divergent Synthesis of Chlorohydrins and Oxaheterocycles via Ir-Catalyzed Asymmetric Hydrogenation,"Chlorohydrins and oxaheterocycles are synthetically valuable building blocks for diverse natural products and therapeutic substances. A highly efficient Ir/ f -phamidol-catalyzed asymmetric hydrogenation of ω-chloroketones was successfully developed, and various chlorohydrins and oxaheterocycles were obtained divergently with excellent yields and enantioselectivities (up to >99% yield and >99% ee). Synthetic utilities of this divergent transformation were demonstrated by gram-scale synthesis of key intermediates of several enantiomerically enriched drugs via this catalytic methodology.",10.1021/acs.orglett.3c02565,2023-09-11,0.6003310060873208
Synthesis,Synthesis of (±)-Crispine A via a Nitrosoalkene Hetero-Diels-Alder Addition to Ethyl Vinyl Ether,"The synthesis of (±)-crispine A in 9 steps and 24% overall­ yield was achieved using a nitrosoalkene hetero-Diels-Alder­ addition to ethyl vinyl ether as the key step. The synthesis starts from commercial 3,4-dimethoxyphenylacetic acid and uses simple methods, easily accessible materials and inexpensive reagents. An isochroman derivative was unexpectedly formed in an attempted reduction of a dihydro-4H-1,2-oxazine intermediate.",10.1055/s-0030-1258333,2010-11-15,0.6003260668026733
Synthesis,Concise Three-Step Strategy for the Synthesis of 2-Benzoxepin-3(1H)-ones,"A short and efficient method was developed for the synthesis of 2-benzoxepin-3(1 H )-ones. The synthetic sequence comprises of initial intermolecular Heck coupling, followed by reduction of the carbonyl functionality of the Heck product and finally base-induced intramolecular condensation. Notably, the final condensation may proceed by an interesting oxy-Michael addition, cycloreversion via double bond isomerization and intramolecular condensation.",10.1055/s-0034-1379901,2015-03-18,0.6003117817705897
Tetrahedron,"Chiral, biomimetic total synthesis of (−)-aplysistatin",,10.1016/s0040-4039(00)85676-2,1982-01-01,0.6003087931633236
Journal of the American Chemical Society,"A Short Synthesis of Delavatine A Unveils New Insights into Site-Selective Cross-Coupling of 3,5-Dibromo-2-pyrone","The recognition of latent symmetry in delavatine A has enabled a short synthesis of the natural product starting from 3,5-dibromo-2-pyrone. The concise synthetic route features a cascade process involving a 6π electrocyclization to construct the indane core of delavatine A. In addition, we have conducted detailed experimental and computational studies to gain an in-depth understanding of the mechanism of the observed site-selective cross-coupling of 3,5-dibromo-2-pyrone. This insight may provide new avenues to achieve the selective cross-coupling of multiply halogenated heteroarenes.",10.1021/jacs.8b13012,2019-01-15,0.600307124068291
Organic Letters,Semisynthesis of an Anticancer DPAGT1 Inhibitor from a Muraymycin Biosynthetic Intermediate,"We have explored a method to convert a muraymycin biosynthetic intermediate 3 to an anticancer drug lead 2 for in vivo and thorough preclinical studies. Cu(OAc) 2 forms a stable complex with the amide 4 and prevents electrophilic reactions at the 2-((3-aminopropyl)amino)acetamide moiety. Under the present conditions, the desired 5″-primary amine was selectively protected with (Boc) 2 O to yield 6 . The intermediate 6 was converted to 2 in two steps with 90% yield.",10.1021/acs.orglett.8b03716,2019-01-30,0.6003034990822951
Tetrahedron,"Synthesis and resolution of a C2-symmetrical indolo-2,3-quinodimethane dimer",,10.1016/s0040-4039(99)01348-9,1999-10-01,0.6002988315378434
Tetrahedron,Synthesis and resolution of 2-hydroxyhexahelicene,,10.1016/j.tetlet.2012.11.036,2012-11-23,0.6002988315378434
Tetrahedron,"Synthesis from D-xylose of the salt marsh caterpillar moth pheromone (3Z,6Z,9S,10R)-epoxyheneicosadiene and its (3Z,6E)-stereoisomer.",,10.1016/s0040-4039(00)96260-9,1987-01-01,0.6002928273720048
Tetrahedron,The synthesis of coumestrol from a flavylium salt,,10.1016/s0040-4039(01)90793-2,1963-01-01,0.6002928273720048
Tetrahedron,Formal synthesis of natural epibatidine and of its enantiomer: Use of radical cyclization in an enantiospecific route,,10.1016/s0040-4039(98)00958-7,1998-07-01,0.600292594514181
Tetrahedron,Efficient synthesis of bongkrekic acid. Three-component convergent strategy,,10.1016/j.tetlet.2009.04.129,2009-05-06,0.6002918810689933
Journal of Organic Chemistry,"An Organocatalyzed Enantioselective Synthesis of (2<i>S</i>,3<i>R</i>,4<i>S</i>)-4-Hydroxyisoleucine and Its Stereoisomers","A concise enantioselective total synthesis of (2S,3R,4S)-4-hydroxyisoleucine and its stereoisomers is described. A key feature of this protocol is a catalytic enantioselective mannich reaction that is either anti- or syn-selective as genesis of chirality.",10.1021/jo100233u,2010-03-22,0.6002882336626978
Organic Letters,First Synthesis of the A/B Ring of Ouabain,[reaction: see text] The synthesis of the fully fuctionalized A/B ring of ouabain has been accomplished efficiently from commercially available starting materials. A key Robinson annulation allows for the building of the desired carbon framework in one high-yielding step. Directed epoxidation followed by selective epoxide opening furnished the final tetraol with the desired all-cis stereochemistry.,10.1021/ol0270881,2002-12-24,0.600274331111587
European Journal of Organic Chemistry,Total Synthesis of α‐Linked Rha–Rha–Gal Undecaprenyl Diphosphate Found in <i>Geobacillus stearothermophilus</i>,Abstract A (2+1) glycosylation approach was employed to construct the core structure of a trisaccharide found in the soil bacterium Geobacillus stearothermophilus . The phospholipid was assembled by the reaction of a peracetylated trisaccharide bearing an anomeric hydroxy group with phosphoramidite and subsequent oxidation to the phosphate. The final coupling step with undecaprenyl monophosphate followed by global acetate deprotection completed the total synthesis of the highly amphiphilic target molecule.,10.1002/ejoc.201101021,2011-09-15,0.6002738769417457
Tetrahedron,"Synthetic studies towards halichondramides, and related novel tris-oxazole containing macrolides from marine organisms. A concise route to the keto-triol formyl enamine moiety.",,10.1016/s0040-4039(00)79858-3,1992-05-01,0.6002631611671181
Journal of the American Chemical Society,Total Synthesis of Dynobactin A,"The first total synthesis of the potent antimicrobial agent dynobactin A is disclosed. This synthesis enlists a singular aziridine ring opening strategy to access the two disparate β-aryl-branched amino acids present within this complex decapeptide. Featuring a number of unique maneuvers to navigate inherently sensitive and epimerizable functional groups, this convergent approach proceeds in only 16 steps (LLS) from commercial materials and should facilitate the synthesis of numerous analogues for medicinal chemistry studies.",10.1021/jacs.3c11560,2024-03-01,0.6002337677482023
Tetrahedron,"A facile enantioselective synthesis of 2-(2-aminoethyl)allylsilanes, new synthons for piperidine synthesis",,10.1016/s0040-4039(03)01428-x,2003-07-01,0.6002328496579008
Journal of Organic Chemistry,Synthesis of Novel 2-Azabicyclo[2.2.0]- and [2.1.1]hexanols,"Methyl- and phenyl-substituted N-(ethoxycarbonyl)-2-azabicyclo[2.2.0]hex-5-enes 6 were reacted with NBS in wet DMSO to afford bromohydrins. Mixtures of unrearranged 6-exo-bromo-5-endo-hydroxy-2-azabicyclo[2.2.0]hexanes 7a,b and rearranged 5-anti-bromo-6-anti-hydroxy-2-azabicyclo[2.1.1]hexanes 8a,b were formed stereoselectively from the parent alkene 6a and 4-methyl alkene 6b. The 5-methyl alkene 6c affords only unrearranged bromohydrin 7c and dibromohydrin 9. By contrast, solely rearranged 3-endo-substituted-2-azabicyclo[2.1.1]hexane bromohydrins 8d-f result from additions to 3-endo-methyl alkene 6d, 3-endo-4-dimethyl alkene 6e, and 3-endo-phenyl alkene 6f. As an alternative route to bromohydrins, the parent 5,6-exo-epoxide 10a and 5-endo-methyl-5,6-exo-epoxide 10b were ring opened with bromine/triphenylphosphine to afford unrearranged 5-endo-bromo-6-exo-hydroxy-2-azabicyclo[2.2.0]hexanes 11a,b, while the 3-endo-methyl epoxide 10c afforded solely the rearranged 5-anti-bromo-6-anti-hydroxy-3-exo-methyl-2-azabicyclo[2.1.1]hexane isomer 8g. Tributyltin hydride reduction of bromohydrins 7a,b and 11a afforded novel 2-azabicyclo[2.2.0]hexan-5-ols 13a,b and -6-ol 14, and bromohydrins 8a,b, 8d-g afforded new 2-azabicyclo[2.1.1]-hexan-5-ols 15a,b and 15d-g.",10.1021/jo001558s,2001-02-14,0.6002287839821971
Journal of Organic Chemistry,Short Scalable Route to Bis-morpholine Spiroacetals and Oxazepane Analogues: Useful 3D-Scaffolds for Compound Library Assembly,"High Resolution Image Download MS PowerPoint Slide sp 3 -Rich molecular scaffolds incorporating nitrogen heterocycles represent important starting points for assembling compound screening libraries and drug discovery. Herein, we report a four-step synthesis of a conformationally well-defined sp 3 -rich scaffold incorporating two morpholine rings embedded within a spiroacetal framework. The synthesis involves the intermediacy of a 2-chloromethyl-substituted morpholine, accessed from epichlorohydrin and readily available β-aminoalcohols. Base-mediated dehydrochlorination affords an exocyclic enol ether, from which the second morpholine ring is constructed in two steps. Scaffold synthesis is high-yielding and can be performed on a large scale. The methodology allows ready substitution of one–or both– of the morpholine rings for 1,4-oxazepanes and the generation of 6,7- and 7,7-spiroacetal analogues, which are virtually unexplored in drug discovery. Substituted 6,6-systems can be prepared and, in some instances, undergo acid-mediated anomerization to deliver the scaffolds in high diastereoselectivity. The two amine functionalities embedded in the 6,6- and 6,7-spiroacetal scaffolds were sequentially functionalized to provide a diverse physical compound library. These library compounds occupy a similar chemical space to small-molecule drugs that have been approved for clinical application by the Food and Drug Administration yet are structurally dissimilar and may therefore act upon novel targets, representing attractive starting materials for drug discovery.",10.1021/acs.joc.4c02690,2025-02-10,0.6002272261251154
Journal of Organic Chemistry,Total Synthesis of the G2/M DNA Damage Checkpoint Inhibitor Psilostachyin C,"A concise total synthesis of the G2/M DNA damage checkpoint inhibitor psilostachyin C is reported using a 1,4-addition-aldol condensation-ring-closing metathesis (RCM) strategy. Initial biological studies indicate that psilostachyin C could enhance the sensitivity of the HeLa cell toward camptothecin (CPT) treatment via the activation of the caspase-3 mediated apoptosis pathway.",10.1021/jo2001275,2011-03-21,0.6002257683146719
Organic Letters,"A Novel, Versatile D→BCD Steroid Construction Strategy, Illustrated by the Enantioselective Total Synthesis of Estrone","A general steroid synthesis is presented that relies on prior formation of three stereogenic centers (C8, C13, and C14) on a D ring template, followed by C- and B-ring cyclizations. The assembly of the key D ring template, achieved by a 3-component conjugate addition/alkylation process, allows introduction of structural variety as required. The method is illustrated by the total synthesis of estrone via a C-ring closing metathesis and a B-ring Heck cyclization.",10.1021/ol902638w,2010-01-22,0.6002233484352189
Synthesis,"Synthesis of Agarofuran Antifeedants, Part II: Stereoselective Construction of the Tetrahydrofuran Ring","All articles of this category This paper describes how to manage the last steps of the synthetic scheme of agarofurans synthesis according to the configurations obtained at C-4a and C-6 during the functionalization of hexahydronaphthalenones derived from a Wieland-Misher ketone in order to obtain either cis - or trans -nor-agarofurans. Synthesis of nor-agarofurans 20 , 24 and 29 are described. antifeedants - agarofuran - Wieland-Mischer ketone - heterocyclisation",10.1055/s-2000-8222,2000-01-01,0.6002232925275769
Journal of the American Chemical Society,Enantioselective Synthesis of (+)-Auriculatol A,"A total synthesis of the grayanane diterpenoid (+)-auriculatol A is reported. The synthesis features a convergent coupling strategy that joins two fragments by a vinylogous Mukaiyama-aldol-type reaction and then constructs the 7-membered ring by a Ni-catalyzed enolate alkenylation. Key findings include the development of a chemoselective Ni-catalyzed intramolecular 1,2-addition to access the bicyclo[3.2.1]octane fragment and the use of electron-deficient olefin supporting ligands as uniquely effective for the Ni-catalyzed enolate alkenylation.",10.1021/jacs.5c17269,2025-11-04,0.6002228004176967
Journal of Organic Chemistry,Total Synthesis of (−)- and (+)-Balanol<sup>1</sup>,"Two total syntheses of the potent protein kinase C inhibitory fungal metabolite balanol are described. In the first approach, the core aminohydroxyazepane subunit was prepared in racemic form by stereospecific functionalization of N-benzyl-epsilon-caprolactam. Resolution prior to coupling to the benzophenone subunit provided access to both enantiomers of balanol. In the second approach, an efficient silicon-mediated cyclization of (2S,3R)-3-hydroxylysine followed by reduction provided the azepane subunit in enantiomerically pure form. The sterically congested benzophenone subunit was assembled from two highly substituted aromatic precursors by way of an anionic homo-Fries rearrangement.",10.1021/jo952280k,1996-01-01,0.600220910737689
Tetrahedron,Anodic oxidation of chiral sulfinylamines: a new route to highly diastereoselective α-alkylation of piperidine,,10.1016/j.tetlet.2005.05.123,2005-06-20,0.6002093604360126
Synlett,Toward the Stereoselective Synthesis of Arthrobotrisin A: Fragment Synthesis and Coupling Studies,"A route towards the stereocontrolled synthesis of arthrobotrisin A based on a Nozaki–Hiyama–Kishi (NHK) coupling strategy was developed. Highlights of the fragment synthesis include enzyme-catalyzed kinetic resolution, Negishi carbometalation–iodination, quinone formation through oxidation with hypervalent iodine, chiral oxazaborolidine-catalyzed asymmetric Diels–Alder reaction with cyclopentadiene, regio- and stereoselective epoxidation, Noyori reduction, retro-Diels–Alder reaction, diastereoselective Luche reduction, and, finally, a Nozaki–Hiyama–Kishi (NHK) coupling of the vinyl iodide fragment.",10.1055/s-0036-1588950,2017-02-24,0.6002039825038498
Journal of Organic Chemistry,Synthesis of (<i>R</i>)- and (<i>S</i>)-Fmoc-Protected Diethylene Glycol Gamma PNA Monomers with High Optical Purity,"A robust synthetic route has been developed for preparing optically pure, Fmoc-protected diethylene glycol-containing ( R )- and ( S )-γPNA monomers. The strategy involves the application of 9-(4-bromophenyl)-9-fluorenyl as a temporary, safety-catch protecting group for the suppression of epimerization in the O -alkylation and reductive amination steps. The optical purities of the final monomers were determined to be greater than 99.5% ee, as assessed by 19 F-NMR and HPLC. The new synthetic methodology is well-suited for large-scale monomer production, with most synthetic steps providing excellent chemical yields without the need for chromatographic purification other than a simple workup and precipitation.",10.1021/acs.joc.8b02714,2019-01-04,0.6002006730597905
Tetrahedron,Enantioselective total synthesis of the polyketide natural product (−)-EI-1941-2: a novel interleukin-1β converting enzyme (ICE) inhibitor,,10.1016/j.tetlet.2005.09.086,2005-10-03,0.6001901478516785
Tetrahedron,Formal total synthesis of hemibrevetoxin B by a convergent strategy,,10.1016/j.tetlet.2004.05.020,2004-06-01,0.6001825660475687
Synlett,A Concise Synthesis of Trifluoromethyl-Substituted 4-Aryloxy Pyrazoles,An efficient route to 4-aryloxy pyrazoles bearing a tri­fluoromethyl group has been developed. A facile removal of the N-hydroxyethyl group has also been developed.,10.1055/s-2006-939703,2006-05-22,0.6001744290366721
Tetrahedron,Synthesis of fused azacycle via Overman rearrangement and ring-rearrangement metathesis as key steps,,10.1016/j.tetlet.2016.03.087,2016-03-30,0.6001730374787184
Organic Letters,"One-Pot Synthesis of Substituted 2,2′-Bipyrroles. A Straightforward Route to Aryl Porphycenes","A one-pot reaction for the synthesis of 4,4'-diaryl- and 4,4'-diheteroaryl-substituted 2,2'-bipyrroles is described. The new methodology is based on the oxidative coupling of a 2-trimethylstannylated pyrrole and does not require chromatography. These 2,2'-bipyrroles can be used as precursors in a expeditious synthesis of 2,7,12,17-tetraaryl-porphycenes.",10.1021/ol802380g,2008-12-03,0.6001683991730267
Organic Letters,Biomimetic Total Synthesis of Dispirocochlearoids A–C and Related <i>Ganoderma</i> Meroterpenoid Dimers,"High Resolution Image Download MS PowerPoint Slide The first total synthesis of the anti-inflammatory Ganoderma meroterpenoid dimers dispirocochlearoids A–C, along with five of their diastereomers─potential unreported natural products─has been accomplished using a convergent strategy that leveraged common intermediates derived from dayaolingzhiol M. The synthesis features several key steps: a hetero-Diels–Alder reaction, a hydrolysis/double-bond migration cascade to assemble the D/E–bicyclic core, and a condensation/intramolecular aldol/lactonization cascade that constructs the final B/C–bicyclic system of dispirocochlearoids A–C.",10.1021/acs.orglett.5c04234,2025-12-12,0.6001540023016396
Tetrahedron,A new general route to olefins from selenides,,10.1016/s0040-4039(01)86553-9,1979-01-01,0.6001503393936997
Synlett,Simple Syntheses of Seven-Membered Rings via an Entropy/Strain Reduction Strategy,"The straightforward four-step synthesis of unsaturated seven-membered carbocycles and heterocycles via a route starting from catechols and quinones is described. The route is based on the Perkin ring-closure reaction and was designed to alleviate the usual problems associated with the formation of medium rings. This is achieved through the presence of unsaturation in the starting mater­ial, which alleviates ring strain problems, reduces the entropy of ­activation and ensures that the chain ends are suitably orientated to encourage ring closure.",10.1055/s-2004-820029,2004-01-01,0.6001480429483944
Angewandte Chemie International Edition,Total Synthesis of (+)-Gelsedine,"A novel iodide-promoted, allene-terminated cyclization of an N-acyliminium ion, a stereoselective Heck spirocyclization, and a chemoselective demethylation at the nitrogen atom of an oxindole are the key transformations in the first total synthesis of the indole alkaloid (+)-gelsedine (1). This dextrorotatory form of natural gelsedine was formed as a single enantiomer in 21 steps from (S)-malic acid.",10.1002/(sici)1521-3773(19990802)38:15<2214::aid-anie2214>3.0.co;2-v,1999-08-02,0.6001456321974189
Organic Letters,Enantioselective Synthesis of α-Amino Phosphonates via Pd-Catalyzed Asymmetric Hydrogenation,"A highly enantioselective palladium-catalyzed hydrogenation of a series of linear and cyclic α-iminophosphonates has been achieved, providing efficient access to optically active α-aminophosphonates with up to 99% ee.",10.1021/acs.orglett.5b03664,2016-02-01,0.6001333400870748
Tetrahedron,Palladium-mediated cyclisation on carbohydrate templates A new route to bis-annulated pyranosides,,10.1016/0040-4039(95)02096-9,1996-01-01,0.6001329371334732
Organic Process Research & Development,Development of Asymmetric Transfer Hydrogenation with a Bifunctional Oxo-Tethered Ruthenium Catalyst in Flow for the Synthesis of a Ceramide (<scp>d</scp>-<i>erythro</i>-CER[NDS]),"The development of an efficient synthetic route for an optically active ceramide compound ( d - erythro -CER[NDS]) is described. The route proceeds through asymmetric transfer hydrogenation in a pipes-in-series flow reactor with oxo-tethered ruthenium complex-catalyzed dynamic kinetic resolution. This synthesis was accomplished without any expensive reagents, and none of the intermediates required isolation. This resulted in a robust process that has been successfully run on a production scale.",10.1021/acs.oprd.8b00338,2018-11-22,0.6001264675865365
Journal of Organic Chemistry,"Asymmetric Syntheses of (−)-8-<i>e</i><i>pi</i>-Swainsonine Triacetate and (+)-1,2-Di-<i>e</i><i>pi</i>-swainsonine. Carbonyl Addition Thwarted by an Unprecedented Aza-Pinacol Rearrangement","Indolizidines (-)-8-epi-swainsonine triacetate and (+)-1, 2-di-epi-swainsonine were synthesized from the O'Donnell Schiff base ester 1 derived from D-serine. Reductive-alkenylation of 1 with (i)()Bu(5)Al(2)H/H(2)C=CHMgBr followed by substrate-directed dihydroxylation of the pendant allylic group with OsO(4), reduction of imine, and cyclization with Ph(3)P/CCl(4) gave the polyhydroxylated pyrrolidines 8a and 8b as advanced intermediates. Efficient protecting group manipulations converted pyrrolidines 8a and 8b to their corresponding partially protected analogues 10a and 10b, which upon Swern oxidation and diastereoselective Keck-type allylation with BF(3).Et(2)O afforded the required three-carbon homologues (10a, >20:1 de; 10b, 3.5:1 de). Use of the chelating Lewis acid MgBr(2) instead of BF(3).Et(2)O with 10a led to a novel aza-pinacol rearrangement and allylation at the alpha-carbon to yield amino alcohol 17, which is similar to a hydride migration in the biosynthetic pathway of indolizidine alkaloids. Subsequent hydroboration, cyclization, and deprotection furnished (-)-8-epi-swainsonine triacetate 15a and (+)-1,2-di-epi-swainsonine 16b in good overall yields (6.3% for 1 --> 15a, 13 steps, and 4.0% for 1 --> 16b, 14 steps).",10.1021/jo000527u,2000-08-10,0.6001256662664844
Organic Letters,Formal Total Synthesis of <i>cis</i>-Sylvaticin and Sylvaticin,"Formal total synthesis of Annonaceae acetogenin natural products cis -sylvaticin and sylvaticin was accomplished from a C 2 -symmetric furyl carbinol. The key reaction in the synthesis is the use of furan as a but-2-ene-1,4-dione synthon, a Donohoe variant of osmium-catalyzed synthesis of 2,5- cis -substituted tetrahydrofuran, and a Mukaiyama oxidative cyclization for the formation of trans -2,5-disubstitued tetrahydrofuran.",10.1021/acs.orglett.5c01501,2025-05-20,0.6001182645604702
Journal of Organic Chemistry,Development of an Asymmetric Synthesis of a Chiral Quaternary FLAP Inhibitor,"A practical sequence involving a noncryogenic stereospecific boronate rearrangement followed by a robust formylation with an in situ generated DCM anion has been developed for the asymmetric construction of an all-carbon quaternary stereogenic center of a FLAP inhibitor. The key boronate rearrangement was rendered noncryogenic and robust by using LDA as the base and instituting an in situ trapping of the unstable lithiated benzylic carbamate with the boronic ester. A similar strategy was implemented for the DCM formylation reaction. It was found that the 1,2-boronate rearrangement for the formylation reaction could be temperature-controlled, thus preventing overaddition of the DCM anion and rendering the process reproducible. The robust stereospecific boronate rearrangement and formylation were utilized for the practical asymmetric synthesis of a chiral quaternary FLAP inhibitor.",10.1021/jo502550h,2015-01-06,0.6001175796332787
Tetrahedron,Enantioselective synthesis of (−)-methyl 5-lactylshikimate lactone,"A short synthesis of enantiomerically pure (−)-methyl 5-lactylshikimate lactone 1 from (−)-shikimic acid is described, which, along with NOE measurements, establishes its absolute stereostructure.",10.1016/s0040-4039(00)94365-x,1990-01-01,0.6001133281839375
Organic Letters,Asymmetric Total Synthesis and Stereochemical Revision of Gymnangiamide,"The asymmetric total synthesis of the originally proposed structure of gymnangiamide, a cytotoxic pentapeptide isolated from the marine hydroid Gymnangium regae Jaderholm, has been achieved. Key to the synthesis was the use of asymmetric hydrogenation of alpha-substituted beta-ketoesters through dynamic kinetic resolution for the preparation of nonproteinogenic chiral amino acids. The disparity of the NMR spectra between the synthetic material containing the L-serine residue and the natural product required a revision of the proposed structure.",10.1021/ol900184d,2009-04-08,0.6001109646371264
Organic Process Research & Development,"Continuous Flow Synthesis of the PARP-1/2 Inhibitor HYDAMTIQ: Synthetic Strategy, Optimization, and Green Metrics Evaluation","High Resolution Image Download MS PowerPoint Slide 2-((Dimethylamino)methyl)-9-hydroxythieno[2,3- c ]isoquinolin-5(4 H )-one (HYDAMTIQ), a potent PARP1/2 inhibitor, is currently being evaluated in preclinical trials for the treatment of ischemia and inflammatory diseases. The current batch synthesis, which includes a Suzuki-Miyaura reaction, a thermal cyclization, and a Mannich-type reaction, makes it a challenging target to prepare on a multigram scale and support compound development. Herein, a telescoped continuous flow synthesis of the key thieno[2,3- c ]isoquinolin-5(4 H )-one scaffold and much improved chromatography-free, downstream steps for HYDAMTIQ have been developed. Assessment of quantitative green metrics confirms the improved efficiency and sustainability of the newly developed flow route, providing a straightforward and versatile approach for scale-up and medicinal chemistry investigations.",10.1021/acs.oprd.3c00295,2023-11-14,0.6001082509982218
Tetrahedron,"Efficient synthesis of chiral phenethylamines: preparation, asymmetric hydrogenation, and mild deprotection of ene-trifluoroacetamides",,10.1016/j.tetlet.2006.06.135,2006-08-07,0.6001071283194672
European Journal of Organic Chemistry,Total Synthesis of (±)‐Englerin A and Its Tuncated Analogues,"A convergent approach allowed total synthesis of (±)‐Englerin A, and its truncated analogues, employing a thermal 1,3‐dipolar cycloaddition of a highly substituted pyrylium ylide with vinyl acetate as the key step. The key intermediate, a 8‐oxabicyclo[3,2,1]octane oxygenated at the C6 position, was directly converted into a truncated Englerin A analogue. Cu I catalyzed conjugate addition of vinyl Grignard to an enone, ozonolysis, and epimerisation of the resulting aldehyde allowed stereoselective introduction of the side‐chain leading to a total synthesis of the racemic natural product. The developed chemistry will allow synthesis of more complex analogues of the natural product based on the use of the key bicyclo[3,2,1]octane scaffold.",10.1002/ejoc.201801544,2019-01-25,0.6000927204079346
Synthesis,A Chiron Approach to (-)-Tetrahydrolipstatin,"An efficient chiron approach to the total synthesis of (-)-tetrahydrolipstatin is described. The main features of the synthetic strategy, which starts from tri-O-acetyl-d-glucal, are copper-mediated­ C-C bond formation, Frater alkylation, and Barton-McCombie­ deoxygenation.",10.1055/s-2006-950325,2006-11-01,0.6000827366432854
Synlett,A Convergent Total Synthesis of (+)-Febrifugine,Key words total synthesis - allyltitanation - Wittig reaction - febrifugine - antimalarial activity,10.1055/s-2008-1072736,2008-04-25,0.6000821814369726
Tetrahedron,Reductive alkylation of urea: A practical route to substituted ureas,,10.1016/s0040-4039(97)10816-4,1998-03-01,0.6000814726439853
Organic Letters,"Enantioselective Synthesis of a GPR40 Agonist AMG 837 via Catalytic Asymmetric Conjugate Addition of Terminal Alkyne to α,β-Unsaturated Thioamide","A concise enantioselective synthetic route to a potent GPR40 agonist AMG 837 is described. The crucial catalytic asymmetric conjugate addition of terminal alkyne was promoted by a soft Lewis acid/hard Brønsted base cooperative catalyst, allowing efficient construction of the requisite stereogenic center. The thioamide functional group is key to both activation in asymmetric alkynylation and facile transformation into carboxylic acid.",10.1021/ol102998w,2011-02-03,0.6000776324915174
Tetrahedron,"Synthesis of sulfated β-1,6-linked oligosaccharide mimetics: A novel potent inhibitor of HIV replication","A novel sulfated β(1→6)-linked oligosaccharide mimetics has been synthesized and found to be a potent inhibitor of HIV replication, with an IC50 of 1 μM.",10.1016/0040-4039(96)00327-9,1996-04-01,0.600074560251799
Tetrahedron,"1,4-benzodioxin chemistry : A new route to C-3 functionalized 2-methylene-1,4-benzodioxans",,10.1016/s0040-4039(00)99540-6,1989-01-01,0.6000717648554837
Journal of Organic Chemistry,Xanthone Natural Products via <i>N</i>-Heterocyclic Carbene Catalysis: Total Synthesis of Atroviridin,"The total synthesis of atroviridin has been accomplished by a linear route involving the N-heterocyclic carbene (NHC)-catalyzed aroylation of the fluorobenzene derivative, Claisen cyclization of the O-propargylated benzophenones, and intramolecular 1,4-addition of the quinone intermediates. The result provides a viable route to xanthone natural products.",10.1021/jo200303c,2011-04-06,0.6000601383825401
Organic Process Research & Development,Process Development and Scale-up of Fully Synthetic Tetracycline TP-2758: A Potent Antibacterial Agent with Excellent Oral Bioavailability,"Process research and development of the fully synthetic broad spectrum tetracycline TP-2758, with a chiral pyrrolidine side chain at the C-8 position, is described. The process utilizes two key intermediates, 7 and 10, in a convergent approach that allows for manufacturing of sufficient quantities of API to supply preclinical and early clinical development. The pyrrolidine moiety was introduced into the left-hand piece (LHP) 10 with high enantioselectivity using Ellman’s sulfinamide chemistry, and the absolute configuration was confirmed by X-ray crystal structure analysis.",10.1021/acs.oprd.5b00404,2015-12-28,0.6000564706554519
Journal of Organic Chemistry,"Asymmetric Reduction of a 1,5-Benzothiazepine Derivative with Sodium Borohydride−(<i>S</i>)-α-Amino Acids:  An Efficient Synthesis of a Key Intermediate of Diltiazem","A key intermediate of diltiazem synthesis, (2 S,3 S )-2,3-dihydro-3-hydroxy-2-(4-methoxyphenyl)-1,5-benzothiazepin-4(5 H )-one [(2 S,3 S )- 1 ], has been efficiently synthesized by an asymmetric reduction of the prochiral ketone, 2-(4-methoxyphenyl)-1,5-benzothiazepine-3,4(2 H,5 H )-dione ( 3 ), with NaBH 4 and chiral α-amino acids. As the chiral sources, β-branched-chain amino acids, such as ( S )-valine, ( S )-isoleucine, and ( S )- tert -leucine, were found to be effective. In particular, using ( S )- tert -leucine as a ligand resulted in the formation of (2 S,3 S )- 1 with excellent enantioselectivity. (95% ee for cis -isomers). The addition of AcOH to the reaction permitted further improvement of both conversion and stereoselectivity. As a result, optically pure (2 S,3 S )- 1 could be isolated in 86% yield. This asymmetric reduction proceeded via dynamic kinetic resolution and made it possible to control the two adjacent asymmetric carbons through keto−enol tautomerism.",10.1021/jo960950w,1996-01-01,0.6000534735651979
Synlett,Formal Total Synthesis of (±)-Conduramine E Utilising the Bryce-Smith-Gilbert Photoamination Reaction,"Utilising a Bryce-Smith-Gilbert photoamination of benzene as a key step, a synthesis of ()-conduramine E was carried out. A highly regioselective dihydroxylation of a cyclic diene was effected utilising Sharpless AD-mix-b.",10.1055/s-0029-1219526,2010-02-11,0.6000518315335555
Organic Letters,"Diastereoselective Synthesis of (2<i>S</i>,5<i>R</i>)-5-Hydroxypipecolic Acid and 6-Substituted Derivatives","[reaction: see text] Herein, we report a diastereoselective synthesis of the natural product (2S,5R)-5-hydroxypipecolic acid and 6-substituted derivatives thereof. The key step in the synthetic sequence is a novel highly diastereoselective epoxidation reaction of an enantiomerically pure cyclic enamide intermediate.",10.1021/ol047774v,2004-11-23,0.6000446687855916
Tetrahedron,"Synthesis of 1-(1-D-car☐y-2-methylpropyl)3-L-(5-L-aminoadipamido)-4-L-mercaptoazetidin-2-one (seco-isopenicillin N), a potential intermediate in penicillin biosynthesis.",,10.1016/s0040-4039(00)88064-8,1983-01-01,0.6000388617654788
Tetrahedron,"Regioselective, intramolecular oxyselenation as a route to the tetrahydrofuran units of boromycin and aplasmomycin",,10.1016/0040-4039(84)80101-x,1984-01-01,0.6000375937225444
Tetrahedron,The preparation of acylacetylenic derivatives of α-cyclocitral on route to physiologically active terpenes,,10.1016/s0040-4039(01)93538-5,1979-01-01,0.6000365233530742
Synthesis,Synthesis of 3′-Deoxy-3′-difluoromethyluridine and 2′-Deoxy-2′-difluoromethyluridine,"The synthesis of 3’-deoxy-3’-difluoromethyluridine (9) and 2’-deoxy-2’-difluoromethyluridine (7β) by hydrogenation of the corresponding difluoromethylene derivatives is described. A second synthesis of the latter has been performed. Starting from thymidine, a two-step procedure affords the benzylated furanoid glycal 12. Addition of dibromodifluoromethane gives the α-2’-deoxy-2’-bromodifluoromethylarabinose (13). This compound allowed an access to α- or β -2’-deoxy-2’-difluoromethyluridine via a SN2 type reaction on a α-halodeoxyarabinose species.",10.1055/s-2001-13419,2001-01-01,0.6000339931681689
Tetrahedron,"Enzymatic Single-step Formation of Laureatin and Its Key Intermediate, Prelaureatin, from (3Z, 6S, 7S)-Laurediol",,10.1016/0040-4039(92)88128-r,1992-04-01,0.6000332230129858
Organic Letters,Total Synthesis of (±)-Hapalindole Q,"[reaction: see text] The total synthesis of the antibacterial and antimycotic alkaloid hapalindole Q has been achieved in eight steps and 12.4% overall yield. The key step involves a regio- and diastereoselective Diels-Alder reaction to afford a bicyclo[2.2.2]oct-2-ene. This cycloadduct was subsequently dihydroxylated, cleaved, and converted to the natural product.",10.1021/ol0165138,2001-09-08,0.6000212292045987
Synlett,A New Synthetic Key Intermediate for Prostaglandins and Prostacyclins from Levoglucosan,All articles of this category Synthesis of the optically active common intermediate 1 for primary PGs and prostacyclin analogues starting from levoglucosan ( 7 ) was described. Prostaglandin - Prostacyclin - Optically Active Common Intermediate - Levoglucosan - Diaxial Ring Opening,10.1055/s-1995-4944,1995-03-01,0.6000192500462164
Organic Letters,"Concise, Stereoselective Approach to the Spirooxindole Ring System of Citrinadin A",The spirooxindole ring system of citrinadin A has been synthesized with excellent control over the absolute stereochemistry at the spirocenter. The key step involves a novel diastereoselective DMDO-mediated oxidative rearrangement employing an 8-phenylmenthol chiral auxiliary on the indole nitrogen.,10.1021/ol702132v,2007-10-01,0.6000186648896471
Organic Process Research & Development,"Research and Development of an Efficient Process for the Construction of the 2,4,5-Substituted Pyridines of NK-1 Receptor Antagonists","Roche has identified a 2,4,5-trisubstituted pyridine template for a new class of potent NK 1 receptor antagonists. Previous strategies for construction of the pyridine core of these NK-1 receptor antagonists involved functionalization of a 2,5-disubstituted pyridine. We now report on construction of the pyridine core from commodity components. Shestopalov reported the synthesis of trans -4‘-aryl-5‘-cyano-1‘,2‘,3‘,4‘-tetrahydro-6‘-hydroxy-2‘-oxo-1,3‘-bipyridinium inner salts from 1-(2-amino-2-oxoethyl)pyridinium chloride, aromatic aldehydes, and ethyl cyanoacetate in the presence of a base. Reaction of these salts with phosphorus oxychloride affords 4-aryl-3-cyano-2,6-dichloropyridines. These are efficiently converted to nicotinamide precursors of the Roche NK-1 receptor antagonists by regioselective displacement of one chlorine by an amine, hydrogenolysis of the remaining chlorine, and nitrile hydrolysis.",10.1021/op060128m,2006-10-26,0.6000186081787324
Tetrahedron,A general route for the synthesis of enantiopure indolizidine alkaloids from α-amino acids. Total synthesis of (+)-Monomorine,,10.1016/s0040-4039(00)60596-8,1993-06-01,0.6000099485961585
Synlett,"Partial Synthesis of Ciguatoxin, an A/B/C Fragment",All articles of this category Synthesis of A/B/C Fragments of ciguatoxin was achieved from a glucose derivative in an optically active form. The key steps were C-glucosidation of silyl acetylene to D-xylal and the cation cyclization through the acetylene biscobalthexacarbonyl complex. Title compound was synthesized in an optically active form via such key steps as C-glucosidation of silylacetylene to D-xylal and cation cyclization through the acetylene biscobalthexacarbonyl complex.,10.1055/s-1996-5436,1996-04-01,0.6000057250473896
Organic Letters,"Studies toward the Total Synthesis of Gambieric Acids, Potent Antifungal Polycyclic Ethers:  Convergent Synthesis of the CDEFG-Ring System","[reaction: see text] A convergent synthetic route to the CDEFG-ring system of gambieric acids, potent antifungal polycyclic ether marine natural products, has been developed. The present synthesis features convergent union of the CD- and G-rings through esterification, formation of the E-ring as a lactone form, stereoselective allylation to set the C26 stereocenter, and ring-closing metathesis reaction to construct the nine-membered F-ring.",10.1021/ol050760k,2005-05-17,0.600004324613179
Organic Letters,"Concise, Stereocontrolled Synthesis of the Citrinadin B Core Architecture","A concise, stereocontrolled synthesis of the citrinadin B core architecture from scalemic, readily available starting materials is disclosed. Highlights include ready access to both cyclic tryptophan tautomer and trans-2,6-disubstituted piperidine fragments, an efficient, stereoretentive mixed Claisen acylation for the coupling of these halves, and further diastereoselective carbonyl addition and oxidative rearrangement for assembly of the core.",10.1021/ol2020362,2011-09-06,0.6000039901008426
Tetrahedron,Synthesis of a novel prostaglandin containing heteroatoms in the ring cyclopentane,,10.1016/s0040-4039(01)01861-5,2001-12-01,0.5999895733761204
Tetrahedron,Synthesis in the series of diterpene alkaloids VIII. A stereospecific synthesis of pentacyclic intermediates with a bridge in ring B,,10.1016/s0040-4039(01)98922-1,1968-01-01,0.5999831376429902
Organic Letters,Total Synthesis of the Antiviral Marine Natural Product (−)-Hennoxazole A,"[structure:see text] The marine natural product hennoxazole A was synthesized by a convergent approach. The diastereoselective Mukaiyama aldol reaction with beta-alkoxy aldehyde was used to construct the tetrahydropyran segment, and the preparation of the nonconjugated triene moiety was accomplished via S(N)2 displacement of allylic bromide with vinyllithium and Takai's iodoolefination followed by palladium-catalyzed cross coupling with MeMgBr. The final steps involve an amide coupling using DEPC and oxazole synthesis via a oxidation/cyclodehydration process.",10.1021/ol000305i,2000-12-01,0.5999809652385704
Journal of Organic Chemistry,Biomimetic Total Syntheses of Cassiarins A and B,"Total syntheses of cassiarins A and B have been efficiently accomplished using a common strategy with biomimetic considerations. Key reactions involved in this synthesis include a Negishi-type coupling, a Ag(I)-promoted formation of the tricyclic 8H-pyrano[2,3,4-de]chromen-8-one core, and a sequential amine-condensation and cyclization. Three new analogues of cassiarin A bearing different substituents at the C-11 position were synthesized in parallel from the same intermediate. In addition, two other transformations to the key tricyclic cores and cassiarins A and B were achieved from corresponding chemically equivalent precursors.",10.1021/jo801017b,2008-06-21,0.5999787264764315
Journal of Organic Chemistry,Asymmetric Synthesis of an Axially Chiral Antimitotic Biaryl via an Atropo-Enantioselective Suzuki Cross-Coupling,"A catalytic asymmetric synthesis of the axially chiral bridged biaryl (-)-2, a structural analogue of natural (-)-rhazinilam possessing original antimitotic properties, is described. The key step is an intermolecular asymmetric Suzuki coupling, furnishing the nonbridged biaryl (-)-6, precursor of (-)-2, with up to 40% ee using binaphthyl ligand 7a. Various known or new binaphthyl and ferrocenyl phosphines as well as phosphetanes were screened as ligands in this reaction, the conditions of which were optimized. The comparison with another Suzuki coupling system showed that 7a is the most versatile ligand described to date for this type of transformation. This work gives the first application of the asymmetric Suzuki coupling to a biologically relevant target.",10.1021/jo034298y,2003-05-21,0.5999746901599036
Tetrahedron,"Asymmetric synthesis of 1α,25-dihydroxyvitamin D3 A-ring precursor starting with 5-tert-butyldimethylsiloxy-2-cyclohexenone",,10.1016/s0040-4039(00)00169-6,2000-04-01,0.5999727197050209
Angewandte Chemie International Edition,Synthetic Approaches to a Molecular Borromean Link: Two‐Ring Threading with Polypyridine Templates,"“One ring to bind them”: The Borromean link, which consists of three rings connected such that no two are concatenated, is a challenging synthetic target. The synthesis of an orthogonal two-ring system that could be a precursor for such a link was prepared from a polypyridine template (see picture).",10.1002/anie.200352562,2003-11-25,0.5999671676683317
Synthesis,Iron-Mediated Complete Chirality Transfer in Allylic Substitutions. Efficient Synthesis of (-)-(<i>S</i>)-Myoporone,"All articles of this category The furanosesquiterpenoid (-)-( S )-myoporone [( S )- 10 ], a toxic stress metabolite of sweet potatoes ( Ipomoea batatas ) and normal secondary metabolite of the australian shrub Myoporum deserti has been synthesized in high enantiomeric purity ( ee > 99 %) and excellent overall yield. Key step in the synthesis is the regio- and stereocontrolled addition of the silyl enol ether 3 to the planar chiral tetracarbonyliron(1+) complex (1 R ,2 S ,3 R )- 2 easily obtained from ( S )-lactic acid.",10.1055/s-1994-25689,1994-01-01,0.5999656708199785
Angewandte Chemie International Edition,Enantioselective Total Synthesis of (−)‐Jiadifenolide,"Neurofunk: Highlights of the synthesis of 1, a potent modulator of neurotrophic factors, include construction of the B ring through an asymmetric Robinson annulation, assembly of the E ring lactone through a novel acid-induced cascade reaction, and Pd0-mediated carbomethoxylation and methylation reactions for the construction of the C and A rings, respectively.",10.1002/anie.201100313,2011-03-11,0.5999623949661279
Tetrahedron,"A short synthesis of +− 2-acetyl-5-8-dimethoxy-1,2,3,4-tetrahydro-2-naphthol - a key intermediate for anthracyclinone synthesis",,10.1016/s0040-4039(00)85604-x,1982-01-01,0.5999538888031
Synthesis,"Practical and Efficient Synthesis of Tris(4-formylphenyl)amine, a Key Building Block in Materials Chemistry","A short, practical and efficient preparation of tris(4-formylphenyl)amine, a key building block in materials chemistry, is described. It involves a two-flask synthesis from triphenylamine, which requires shorter overall time than the direct one-flask threefold Vilsmeier-Haack formylation, while giving higher yields. The reaction levels off at the disubstitution stage, due to the deactivation of the bis-iminium intermediate, but hydrolysis of the latter into a less deactivated dialdehyde allows the third formylation to occur. The simple experimental protocol makes this method more convenient than the previously reported procedures.",10.1055/s-2005-865336,2005-01-01,0.5999517716814251
Organic Letters,"Asymmetric Construction of the Core of C<sub>6</sub>, C<sub>7</sub>-Epoxy Daphnane Diterpenoid Orthoesters","-epoxy daphnane diterpenoid orthoesters is developed through a convergent synthetic strategy. The salient features include a diastereoselective nucleophilic assembly of two bulky cyclic fragments, an oxidative cleavage/transesterification/aldol cascade to fashion the seven-membered ring, and a base-mediated transesterification/retro-aldol/aldol/epoxidation cascade to install the epoxy moiety with proper stereochemistry.",10.1021/acs.orglett.3c03136,2023-11-02,0.5999433699266433
Organic Letters,Synthetic Studies on Pactamycin: A Synthesis of Johnson’s Intermediate,"A formal total synthesis of pactamycin ( 1 ) has been accomplished by face-selective and regioselective nitroso Diels–Alder (NDA) reaction of acyl nitroso compound 14, which contains a camphorsultam chiral auxiliary, and chiral cyclopentadiene 12 . Construction of the chiral secondary alcohol of 12 was performed by ( S, S )-Ts-DENEB catalyst-mediated reduction, and the NDA adduct 15a was readily converted to Johnson’s intermediate 21 .",10.1021/acs.orglett.0c00959,2020-04-22,0.5999409862252186
Tetrahedron,Selective reduction and cleavage of the N-N bond of fused tetrahydropyridazines: a route to functionalised lactams,,10.1016/s0040-4039(01)81045-5,1987-01-01,0.5999296819776122
Journal of the American Chemical Society,Total Synthesis and Proof of Structure of a Human Breast Tumor (Globo-H) Antigen,"The total synthesis of the Hakomori MBr1 antigen, heavily expressed on human breast tumors, is related. The construction involved the assembly of four glycals: ( 17 (twice), 18, 20, and 26 ) and an l -fucose derivative, 34 . The sensitivity of the stereochemistry of sulfonamido galactosylation by a terminal galactose ring as a function of the state of protection status of its C 4 alcohol was exploited in a key step. (See the formation of compound 51 .) The synthesis served to confirm the Hakomori assignment of structure, and paves the way for immunoconjugation. (See compound 64 .)",10.1021/ja962048b,1996-01-01,0.5999249581894137
Synlett,Highly Efficient Diastereoselective Synthesis of Azabicyclo[2.2.2]octanes,"A one-pot, diastereoselective synthesis of diverse azabicyclo[2.2.2]octanes from readily available starting materials is reported. The key strategy relies on creation of 2-aminoprop-1-ene-1,1,3-tricarbonitrile through dimerization of malononitrile which undergoes nucleophilic attack on dibenzalacetone at three sites leading to bicyclo[2.2.2]octanes.",10.1055/s-0034-1379204,2014-10-07,0.5999246495437687
Synlett,Synthesis of New γ-Lactams with gem-Difluorinated Side Chains,"A short and efficient approach has been designed for the synthesis of new γ-lactams that feature gem-difluorinated side-chains in position 4. The key steps involve 1,4-addition of nitroalkane anions on electrophilic gem-difluoroalkenes, followed by a cascade nitro reduction–heterocyclization. This flexible strategy also allows easy introduction of substituents in positions 3 or 5.",10.1055/s-0039-1690715,2019-10-14,0.5999204729621924
Synlett,A Bridgehead Carbocation Fragmentation Leading to the Taxane AB Ring System,"All articles of this category The AB ring system was constructed from cyclohexane-1,3-diones by a direct route. The key steps included an intramolecular photocyclization and a fragmentation of a bridgehead carbocation.",10.1055/s-1993-22353,1993-01-01,0.5999200565058943
Journal of Organic Chemistry,Stereodivergent Synthesis of Enantioenriched 4-Hydroxy-2-cyclopentenones,"Protected 4-hydroxycyclopentenones (4-HCPs) constitute an important class of intermediates in chemical synthesis. A route to this class of compound has been developed. Key steps include Noyori reduction (which establishes the stereochemistry of the product), ring-closing metathesis, and simple functional group conversions to provide a set of substituted 4-HCPs in either enantiomeric form.",10.1021/jo402539p,2013-12-10,0.5999110937801342
Tetrahedron,"A novel ring expansion of an n-aminophthalimidine to a condensed dihydrophthalazin-1-one. Synthesis of 1h-pyrazolo[1,2-b]phthalazine derivative",,10.1016/s0040-4039(00)93034-x,1976-01-01,0.5999050635634239
Synthesis,A New Method for the Synthesis of Enantiomerically Pure Betti Base,"We have developed a new method for the synthesis of enantiomerically pure Betti base. By using trifluoroacetic acid to replace the more traditionally used hydrochloride acid, the hydrolysis procedure used in the classical synthesis of racemic Betti base was carried out under milder conditions with an improved yield (up to 96%), which was followed by a new and efficient resolution with using recyclable ( R )-1,1′-binaphthalene-2,2′-diyl sodium phosphate to provide enantiomerically pure ( S )-Betti base in 95% yield with up to 99% ee and ( R )-Betti base in 93% yield with 90% ee in one resolution step.",10.1055/s-0032-1318272,2013-02-13,0.599903960926001
Journal of Organic Chemistry,A Highly Stereospecific and Efficient Synthesis of Homopentafluoro- phenylalanine,"A short and efficient synthesis of homopentafluorophenylalanine (6) from oxazolidine aldehyde 1 in 57% overall yield and in > 98% ee is described. The enantiomeric excess of the product was determined by 19F NMR analysis of the coupling product derived from 5 and L-Ser(O-t-Bu)-OCH3, by comparison to a dipeptide obtained from racemic 5.",10.1021/jo049206z,2004-07-13,0.599898819161357
Journal of the American Chemical Society,Concise Enantioselective Total Synthesis of Daphenylline Enabled by an Intramolecular Oxidative Dearomatization,"natural alkaloids, which exhibit intriguing biological activities. Six total syntheses have been reported, five of which utilize aromatization approaches. Herein, we report a concise protecting-group-free total synthesis by means of a novel intramolecular oxidative dearomatization reaction, which concurrently generates the critical seven-membered ring and the quaternary-containing vicinal stereocenters. Other notable transformations include a tandem reductive amination/amidation double cyclization reaction, to assemble the cage-like architecture, and installation of the other two chiral stereocenters via a highly enantioselective rhodium-catalyzed challenging hydrogenation of the diene intermediate (90% e.e.) and an unprecedented remote acid-directed Mukaiyama-Michael reaction of the complex benzofused cyclohexanone (13:1 d.r.).",10.1021/jacs.2c01674,2022-03-15,0.599896686554216
Tetrahedron,A new synthetic approach to the amaryllidaceae alkaloids. Application to the synthesis of mesembrine and mesembrinine.,,10.1016/s0040-4039(01)98974-9,1968-01-01,0.5998942163497714
European Journal of Organic Chemistry,"Synthesis of Diverse 6‐Oxa‐allocolchicinoids by a Suzuki–Miyaura Coupling, Acid‐Catalyzed Intramolecular Transacetalization Strategy","Abstract The synthesis of allocolchicine analogues is of importance as these compounds have been found to possess promising anticancer activity by affecting tubulin polymerization. In this paper, the synthesis of 28 novel substituted 6‐oxa‐allocolchicinoids is reported. The key steps involved in the synthesis were a Suzuki–Miyaura coupling reaction, followed by an acid‐catalyzed intramolecular transacetalization to afford the desired 5‐alkoxy‐5,7‐dihydrodibenzo[ c , e ]oxepines. In addition, when thiophenol and phenol were used in the transacetalization step, the 5‐(phenylsulfanyl)‐5,7‐dihydrodibenzo[ c , e ]oxepine and 4‐(5,7‐dihydrodibenzo[ c , e ]oxepin‐5‐yl)phenol skeletons were obtained, respectively. The cytotoxicity of the synthetic compounds was unfortunately not impressive; however, one of the compounds was shown to sensitize vincristine‐resistant leukemia and lymphoma cells to vincristine, a result vindicating further synthetic studies.",10.1002/ejoc.201500573,2015-07-08,0.5998938681871054
Synthesis,Synthesis of Multifunctionalized 2-Iminothiazolidin-4-ones and Their 2-Arylimino Derivatives,"Multifunctionalized 2-imino-3-(pyrazol-4-yl)thiazolidin-4-ones and 2-arylimino-3-(pyrazol-4-yl)thiazolidin-4-ones were prepared according to an efficient four-step procedure. The key step of the synthetic pathway involved the cyclization of 2-chloro- N -(pyrazol-4-yl)acetamide intermediate using KSCN or aryl isothiocyanate, respectively. The structure of the title compounds was confirmed on the basis of NMR data and 15 N-labeling.",10.1055/s-0035-1562521,2016-09-09,0.5998887016390114
Tetrahedron,An efficient one-pot route to an aza-bridged bis-phenanthroline macrocyclic compound,,10.1016/s0040-4039(00)01525-2,2000-10-01,0.5998841181078981
Tetrahedron,A novel synthetic route to substituted pyranoanthocyanins with unique colour properties,,10.1016/j.tetlet.2003.08.065,2003-09-17,0.5998833384309977
Synlett,Synthesis of Excitatory Amino Acid Analogues,A general route to excitatory amino acid analogues has been developed as exemplified by the synthesis of A-1 and A-2. The key reactions involved were a Negishi coupling of Jackson’s organozinc reagent with vinyl bromide 8 and subsequent ring closure of 15 and 16 using the Mitsunobu reaction.,10.1055/s-2006-950399,2006-09-01,0.5998821795410526
Organic Letters,Synthesis of an Anti-Methicillin-Resistant <i>Staphylococcus aureus </i>(MRSA) Carbapenem via Stannatrane-Mediated Stille Coupling,"[formula: see text] A short synthesis of carbapenem 1 is described. They key step involves the cross-coupling of an enol triflate with an amino-substituted sp3 carbon. This cross-couping, which allows the introduction of the complete side chain in one step, utilizes a stannatrane as the heteroalkyl transfer reagent.",10.1021/ol005641d,2000-03-30,0.5998780031247984
Journal of Organic Chemistry,Design and Enantioselective Synthesis of a Peptidomimetic of the Turn in the Helix−Turn−Helix DNA-Binding Protein Motif,"A peptidomimetic of the turn in the helix-turn-helix (HTH) motif of DNA-binding proteins was designed and synthesized. Conformational constraint was achieved by an unusual linking of two amino acids with a side chain carbon-carbon bond. A phenyl ring provides the potential for new hydrophobic contacts with the hydrophobic core of the HTH motif. In the mimic, the peptide backbone and the central residue were retained in native form within a 12-membered cyclic tripeptide. The target compound 1b was synthesized by two sequential Horner-Wittig couplings followed by enantioselective hydrogenation with Rh(MeDuPHOS) in eight steps and 35% overall yield. The stereochemical outcome of the key hydrogenation was determined by aromatic ring oxidation with RuO(2)/NaIO(4) to give 2 equiv of Boc-Asp-OMe.",10.1021/jo971077h,1997-11-01,0.5998750756276896
Journal of Organic Chemistry,Total Synthesis of a Rare-Sugar-Enriched <i>O</i>-Antigenic Tetrasaccharide Repeating Unit of <i>Acinetobacter lwoffii</i> EK30A,"Herein, we communicate a concise synthetic strategy for the first total synthesis of the O -antigenic tetrasaccharide repeating unit of Acinetobacter lwoffii EK30A polysaccharide. The structurally unique tetrasaccharide possesses three consecutive 1,2- cis -glycosidic linkages and two rare sugar units, i . e ., d -Fuc p NAc and d -Qui p 4NAc. All functionalized monosaccharides were efficiently synthesized from naturally abundant and inexpensive d -galactose to make the synthetic route affordable and convenient. The tetrasaccharide was synthesized using highly stereoselective, convergent (1 + 2 + 1) and carefully optimizing a high-yielding glycosylation strategy.",10.1021/acs.joc.5c00074,2025-03-25,0.5998722143613505
Tetrahedron,"Synthesis of 2S-carboxy-3R,4R,5S-trihydroxypiperidine; a naturally occurring inhibitor of β-D-glucuronidase",,10.1016/s0040-4039(01)80831-5,1985-01-01,0.5998689265339924
Synlett,Practical Synthesis of Telluroglycosides,All articles of this category A new and efficient synthesis of 1-aryltelluroglycoside is described. The reaction of α-bromoglycoside and diaryl ditelluride in the presence of NaBH 4 afforded the corresponding aryl β-telluroglycoside in good to excellent yield. Telluroglycosides - Ditellurides - Bromoglycosides,10.1055/s-1996-5619,1996-09-01,0.599859123630686
Angewandte Chemie International Edition,Total Synthesis of Lucidumone through Convenient One‐pot Preparation of the Tetracyclic Skeleton by Claisen Rearrangement and Subsequent Intramolecular Aldol Reaction,"The total synthesis of lucidumone (1), a Ganoderma meroterpenoid, was accomplished in racemic form from easily prepared 6 and 7 in 10 steps as the longest linear sequence. The synthesis was completed through one-pot preparation of the tetracyclic core skeleton by Claisen rearrangement followed by an intramolecular aldol reaction. The intramolecular aldol reaction allowed for the stereocontrolled construction of the bicyclo [2.2.2] octane skeleton fused to an indanone structure. The enantioselective total synthesis of 1 was also described via a chiral transfer strategy in the Claisen rearrangement.",10.1002/anie.202304132,2023-04-11,0.5998561051196224
Organic Letters,Formal Synthesis of (±)-Dendrobine:  Use of the Amidofuran Cycloaddition/Rearrangement Sequence,The formal synthesis of the alkaloid (+/-)-dendrobine (4) was accomplished using the IMDAF cycloaddition/rearrangement sequence of a furanyl carbamate. Conversion of the rearranged cycloadduct to Kende's advanced intermediate in eight steps completed the formal synthesis of (+/-)-dendrobine.,10.1021/ol006444h,2000-09-13,0.5998452667538482
Angewandte Chemie International Edition,Total Synthesis and Structural Reassignment of Aspergillomarasmine A,"The increase and spread of Gram-negative bacteria that resistant are to almost all currently available β-lactam antibiotics is a major global health problem. The primary cause for drug resistance is the acquisition of metallo-β-lactamases such as metallo-β-lactamase-1 (NDM-1). The fungal natural product aspergillomarasmine A (AMA), a fungal natural product, is an inhibitor of NDM-1 and has shown promising in vivo therapeutic potential in a mouse model infected with NDM-1-expressing Gram-negative bacteria. The first total synthesis and stereochemical configuration reassignment of aspergillomarasmine A is reported. The synthesis highlights a flexible route and an effective strategy to achieve the required oxidation state at a late stage. This modular route is amenable to the efficient preparation of analogues for the development of metallo-β-lactamase inhibitors to potentiate β-lactam antibiotics.",10.1002/anie.201509960,2015-11-23,0.599841340003523
Journal of Organic Chemistry,Total Syntheses of Iheyamines A and B,An efficient synthetic route to iheyamine A and its analogues was discovered; the crucial one-pot transformation included a C-C migration to form the characteristic seven-membered ring. Subsequent addition of acetone to iheyamine A initiated a cascade process to complete the total synthesis of iheyamine B.,10.1021/acs.joc.2c02583,2022-12-29,0.5998317830005067
Organic Letters,Total Synthesis of Gymnothelignan K via a One-Pot Homologative γ-Butyrolactonization,"The first total synthesis of tetrahydrofuran dilignan gymnothelignan K is disclosed. The approach is based on implementing an early stage one-carbon homologative lactonization, which we recently disclosed, for constructing the γ-butyrolactone scaffold with the requisite β,γ- trans -vicinal stereocenters. Other salient features of the synthesis include the acid-promoted dimerization and the Suzuki–Miyaura cross-coupling reaction to install the challenging diaryl skeleton that permits the effective assembly of the optically active gymnothelignan K in 8 steps from commercially available materials.",10.1021/acs.orglett.2c00939,2022-04-12,0.5998303192530019
Synlett,"Synthesis and Application of an Enantiomerically Pure Triflate Analogue of Microbially Derived 3-Halo-cis-1,2-dihydrocatechol Acetonides","(1 S ,2 S )-3-Trifloxy- cis -1,2-dihydrocatechol acetonide, a useful chiral building block, was prepared from d -ribose in good overall yield using a carbonyl allylation and a ring-closing metathesis as the key C–C bond-forming steps. Negishi cross-coupling of this triflate with a serine-derived organozinc iodide proceeded efficiently to afford an α-amino acid derivative as a potential precursor for scabrosin esters (ambewelamides).",10.1055/s-0032-1318214,2013-02-06,0.5998287857767367
European Journal of Organic Chemistry,"Synthesis of New Tetracyclic Ring Systems: Bridged Derivatives of Hydroxy‐, Sulfanyl‐ and Amino‐Substituted Dibenzo[c,<i>f</i>][1,2]Thiazepine <i>S</i>,<i>S</i>‐Dioxides","Abstract In continuation of our commitment to the synthesis of new ring systems based on the 6,11‐dihydrodibenzo[ c , f ][1,2]thiazepine 5,5‐dioxide core of the antidepressant drug tianeptine, we have incorporated two‐ and/or three‐carbon bridges between the nitrogen atom of the sulfonamide moiety and the N ‐, O ‐ or S ‐substituent at position 11 of the tricycle. The synthesis of 5 new ring systems is described and demonstrated with several target compounds.",10.1002/ejoc.202400835,2024-09-27,0.5998268373845925
Journal of Organic Chemistry,Diastereoselective Construction of the 6-Oxa-2-azabicyclo[3.2.1]octane Scaffold from Chiral α-Hydroxyaldehyde Derivatives by the Aza-Prins Reaction,"(R)-2,3-Di-O-benzylglyceraldehyde and N-tosyl homoallylamine undergo aza-Prins cyclization to afford (1R,5S,7S)-7-[(benzyloxy)methyl]-2-tosyl-6-oxa-2-azabicyclo[3.2.1]octane in a highly diastereoselective manner through an unexpected intramolecular nucleophilic attack. Our work has opened a new route toward the asymmetric synthesis of 7-(alkyl or aryl)-6-oxa-2-azabicyclo[3.2.1]octane derivatives from chiral α-hydroxyaldehyde derivatives in one step.",10.1021/acs.joc.7b01291,2017-07-17,0.5998176535870896
Journal of Organic Chemistry,Asymmetric Synthesis of the Functionalized A/E-Ring Fragment of C<sub>18</sub>-Diterpenoid Alkaloids,"-diterpenoid alkaloids is described. The crucial contiguous stereogenic centers at C4, C5, and C11 were established through an asymmetric Michael addition/allylation sequence. The unique azabicyclo[3.3.1]nonane motif (A/E rings) was assembled by employing ring-closing metathesis and Mitsunobu reaction as key strategies.",10.1021/acs.joc.3c02745,2024-02-07,0.5998168469999126
Organic Letters,Concise Total Synthesis of (±)-Lycopladine A,A concise total synthesis of the Lycopodium alkaloid lycopladine A (1) is described that features sequential conjugate addition and enolate arylation reactions to construct the tricyclic core in two steps.,10.1021/ol100273p,2010-03-02,0.5998164723658236
Synthesis,"A Short Efficient Synthesis of 11-Monoacetate of Drimane-8α,11-diol from Norambreinolide","All articles of this category An efficient two-step synthesis of 11-acetoxydrimane-8 α -ol, a valuable intermediate for the synthesis of naturally occurring drimanes, from commercially available norambreinolide, is described. The Baeyer-Villiger oxidation of the initially obtained 8 α -hydroxy-12-oxo-11-homodrimane is considered as the key step. oxidation",10.1055/s-1997-1302,1997-09-01,0.5998118500363208
Organic Letters,Expeditious Total Syntheses of Camptothecin and 10-Hydroxycamptothecin,"New expeditious total syntheses of (S)-camptothecin (16% overall yield, 95% ee) and (S)-10-hydroxycamptothecin (14% overall yield, 99% ee) have been accomplished, respectively, starting from readily available and inexpensive materials. Development, optimization, and successful application of the cascade reaction consisting of a pyrrolidine-catalyzed Michael addition, an intramolecular aldol condensation, and an oxidative aromatization, the intramolecular oxa Diels-Alder cycloaddition, and the Sharpless asymmetric dihydroxylation make these two new syntheses more efficient and straightforward.",10.1021/ol802250y,2008-11-08,0.5998060984998003
Organic Letters,Synthesis of Fluorenes Starting from 2-Iodobiphenyls and CH<sub>2</sub>Br<sub>2</sub> through Palladium-Catalyzed Dual C–C Bond Formation,"A facile and efficient approach is developed for the synthesis of fluorene and its derivatives starting from 2-iodobiphenyls and CH2Br2. A range of fluorene derivatives can be synthesized under relatively mild conditions. The reaction proceeds via a tandem palladium-catalyzed dual C-C bond formation sequence through the key dibenzopalladacyclopentadiene intermediates, which are obtained from 2-iodobiphenyls through palladium-catalyzed C-H activation.",10.1021/acs.orglett.6b01300,2016-05-27,0.5998002661757001
Angewandte Chemie International Edition,"Total Syntheses of Echitamine, Akuammiline, Rhazicine, and Pseudoakuammigine","Echitamine (1) and akuammiline (2) are representative members of a fascinating class of monoterpenoid indole alkaloids. We report the syntheses of 2 and its congener deacetylakuammiline (3). The azabicyclo[3.3.1]nonane motif was assembled through silver-catalyzed internal alkyne cyclization, and one-pot C-O bond cleavage/C-N bond formation furnished the pentacyclic scaffold. Compound 3 then served as a common intermediate for preparing a series of structurally diverse and synthetically challenging congeners including 1. A position-selective Polonovski-Potier reaction followed by formal N-4 migration built the core of N-demethylechitamine (4) and 1. An alternative route featuring Meisenheimer rearrangement gave 4 as well. Oxidation of the alcohol within 3 gave rhazimal (5), which underwent tandem indolenine hydrolysis, hemiaminalization, and hemiketalization to form rhazicine (6). A sequence of N,O-ketalization and reductive amination secured the chemoselectivity of N-methylation, leading to pseudoakuammigine (7).",10.1002/anie.201901086,2019-02-26,0.5997979041635232
European Journal of Organic Chemistry,"Enantioselective Synthesis of Chiral Pyrazolo[3,4‐<i>d</i>]azepin‐7(2<i>H</i>,4<i>H</i>,8<i>H</i>)‐one Derivatives through a Sequential Michael Addition and Reductive Ring‐Closing Strategy","The asymmetric Michael addition of ethyl (5‐oxo‐1‐phenyl‐4,5‐dihydro‐1 H ‐pyrazol‐3‐yl)acetate to nitroalkenes catalyzed by a squaramide organocatalyst to give chiral pyrazoles was studied. Subsequent one‐pot reductive ring closing in the same pot gave a series of biologically important chiral pyrazolones with seven‐membered lactam frameworks in good yields with excellent enantioselectivities (up to 99 % ee ).",10.1002/ejoc.201700443,2017-04-27,0.599797151431285
Angewandte Chemie International Edition,An Ugi Reaction in the Total Synthesis of (−)‐Dysibetaine,"(-)-Dysibetaine has been synthesized in 11 steps from readily available L-malic acid (see scheme). The key step is a unique Ugi 4-center-3-component cyclization reaction, where an ester group acts as the carboxylic acid component. The use of 1,1,1,3,3,3-hexamethyldisilazane as an ammonia equivalent and a specially designed isocyanide leads to an expeditious synthesis.",10.1002/anie.200805709,2009-01-28,0.599793739078525
Synthesis,A Convenient Synthesis of (±)-2-Carboxy-4-(3-phosphonopropyl)piperazine (CPP),"All articles of this category A short and convenient route to the N -methyl-D-aspartate (NMDA) antagonist 2-carboxy-4-(3-phosphonopropyl)piperazine (CPP), involving selective N-4 alkylation of piperazine-2-carboxylic acid esters, is described. The method uses readily available starting materials and is suitable for multigram quantities.",10.1055/s-1992-26301,1992-01-01,0.5997934081356839
Tetrahedron,A novel regioselective synthesis of allylsilanes.,,10.1016/s0040-4039(00)92030-6,1991-02-01,0.5997882902449805
Tetrahedron,Alkaloid synthesis using 2nd generation palladium-catalyzed cycloalkenylation. Diastereoselective total synthesis of α-skytanthine,,10.1016/j.tetlet.2011.08.162,2011-09-03,0.5997851826816571
Synthesis,A Convenient Synthesis of a N-Protected l-carbamoylpolyoxamic Acid Derivative: Total Synthesis of (+)-Polyoxin J and (+)-Polyoxin L,,10.1055/s-1999-3563,1999-09-01,0.5997844075740779
Journal of Organic Chemistry,"Synthesis of a Diacetonide-Protected, Mannose-Based Oxepine: Configurational Control of Anomeric Acetate Activation","Carbohydrate-based oxepines are seven-membered-ring oxacycles containing an enol ether moiety. These compounds have been used as intermediates in the preparation of septanose carbohydrates by functionalization through their double bond. Reported here is a new synthesis of a carbohydrate based oxepine that uses 2,3;4,6-di- O -acetonide mannose as a key starting material. The oxepine is an important precursor used in the synthesis of septanose glycomimetics of mannopyranosides. The central feature of the synthesis is a two-step sequence that converts a septanose 1,2-di- O -acetate to the septanosyl bromide and onward to the oxepine via a reductive elimination.",10.1021/acs.joc.2c00206,2022-05-16,0.5997754376341637
Organic Letters,Catalytic Enantioselective Approach to the Eudesmane Sesquiterpenoids: Total Synthesis of (+)-Carissone,A catalytic enantioselective approach to the eudesmane sesquiterpenoids is reported. The strategic use of a palladium-catalyzed enantioselective alkylation of vinylogous ester substrates forged the C(10) all-carbon quaternary center. This key transformation enabled a diastereoselective olefin hydrogenation to create the syn stereochemistry at C(7). The devised synthetic strategy allowed for the preparation of the antibacterial agent (+)-carissone and a formal synthesis of the P/Q-type calcium channel blocker (-)-alpha-eudesmol.,10.1021/ol802409h,2008-12-18,0.5997751135339591
Journal of Organic Chemistry,"A Synthetic Route to Chiral 1,4-Disubstituted Tetrahydro-β-Carbolines via Domino Ring-Opening Cyclization of Activated Aziridines with 2-Vinylindoles","A simple and efficient strategy for the synthesis of various 1,4-disubstituted tetrahydro-β-carbolines with excellent stereoselectivity (de, ee up to >99%) via domino ring opening cyclization (DROC) of activated aziridines with 2-vinylindoles is described. The reaction proceeds through LiClO 4 -catalyzed Friedel–Crafts-type alkylation of 2-vinylindoles with activated aziridines followed by an intramolecular aza-Michael reaction in a domino fashion.",10.1021/acs.joc.6b02719,2017-02-10,0.5997707788301234
Synlett,Synthesis of the C15-C35 Segment of Chivosazole A,The synthesis of the C15-C35 segment of chivosazole A is reported using a convergent approach that incorporates an E-selective Wittig olefination for joining both subunits of this fragment.,10.1055/s-2007-991049,2007-09-25,0.5997705029755779
Journal of Organic Chemistry,Regioselective Synthesis of C3-Hydroxyarylated Pyrazoles,"Pyrazoles are ubiquitous structures in medicinal chemistry. We report the first regioselective route to C3-hydroxyarylated pyrazoles obtained through reaction of pyrazole N -oxides with arynes using mild conditions. Importantly, this method does not require the C4 and C5 positions of the pyrazole to be functionalized to observe regioselectivity. Using this method, we completed the synthesis of a recently reported JAK 1/2 inhibitor. Our synthesis produces the desired product in 4 steps from commercially available starting materials.",10.1021/acs.joc.1c02518,2021-12-14,0.5997656892974407
Organic Letters,"Selective Synthesis of 1,2-<i>cis</i>-α-Glycosides without Directing Groups. Application to Iterative Oligosaccharide Synthesis","A method for the highly selective synthesis of 1,2-cis-α-linked glycosides that does not require the use of the specialized protecting group patterns normally employed to control diastereoselectivity is described. Thioglycoside acceptors can be used, permitting iterative oligosaccharide synthesis. The approach eliminates the need for lengthy syntheses of monosaccharides possessing highly specialized and unconventional protecting group patterns.",10.1021/ol401095k,2013-05-06,0.5997651403975732
Journal of Organic Chemistry,"Alkyne [2 + 2 + 2]-Cyclotrimerization Approach for Synthesis of 6,7-Cyclopropylallocolchicinoids","Employing a cobalt-catalyzed [2 + 2 + 2] alkyne cyclotrimerization as the final step, the short and efficient synthesis of cyclopropylallocolchicinoid and its analogues having functional group variations at C9 and/or C10 and C11 of ring C has been accomplished.",10.1021/acs.joc.6b00020,2016-03-16,0.599764732428061
Tetrahedron,Efficient and straightforward preparation of a building block for (−)-teubrevin G synthesis via chemically diversed oriented synthesis,,10.1016/j.tetlet.2011.10.112,2011-10-26,0.5997556851698265
Angewandte Chemie International Edition,Total Syntheses of All the Amathaspiramides,Six in one blow: Total syntheses of all the amathaspiramide alkaloids have been accomplished. Rapid construction of the diazaspiro[3.3]nonane core combined with regio- and diastereoselective reduction of the cyclic imide moiety with DIBAL established the route to the common structural motif. The late-stage reduction of the lactam to an imine functionality mediated by Schwartz's reagent was the key to the streamlined syntheses.,10.1002/anie.201109221,2012-01-27,0.5997545130423685
Journal of the American Chemical Society,Enantioselective Total Synthesis of Briarellins E and F:  The First Total Syntheses of Briarellin Diterpenes,"Enantioselective total syntheses of briarellin E (4) and briarellin F (5) have been achieved starting with (S)-(+)-carvone and (S)-(-)-glycidol. These total syntheses are the first of briarellin diterpenes. The central step in these syntheses is acid-promoted condensation of cyclohexadienyl diol 15 and (Z)-alpha,beta-unsaturated aldehyde 16 to form, with complete stereocontrol, the hexahydroisobenzofuran core and six stereocenters of these coral metabolites. These syntheses also feature stereospecific photolytic deformylation of beta,gamma-unsaturated aldehyde 17 to remove the extraneous carbon introduced in the Prins-pinacol step, chemo- and stereoselective hydroxyl-directed epoxidation of dienyl alcohol 18 to incorporate the C3 oxygen stereocenter, regio- and stereoselective rearrangement of epoxy ester 19 to install the C4 oxygen substituent, efficient dehydrative cyclization of a 1,6-diol intermediate to form the oxepane ring, and diastereoselective Nozaki-Hiyama-Kishi cyclization of vinyl iodide aldehyde 25 to forge the oxacyclononane ring and the C6 hydroxyl stereocenter. These total syntheses establish the absolute configurations of 4 and 5, define a concise strategy for the total synthesis of briarellin diterpenes, and provide additional illustrations of the uncommon utility of pinacol-terminated cationic cyclizations for stereocontrolled synthesis of complex oxacyclic natural products.",10.1021/ja035445c,2003-05-07,0.5997541644235795
Journal of Organic Chemistry,A Concise Synthesis of Lentiginosine Derivatives Using a Pyridinium Formation via the Mitsunobu Reaction,A four-step synthesis of (-)-lentiginosine and its epimers is described starting from 2-bromopyridine. The key step consisted of a quaternarization of a fully unprotected pyridinium-polyol unit using Mitsunobu methodology. Subsequent PtO(2)-catalyzed diastereoselective hydrogenation of the pyridinium ring proceeded smoothly and led to the expected dihydroxyindolizidines with excellent yields. This stereochemically flexible strategy has been illustrated by the concise total synthesis of non-natural products derivatives such as (-)-lentiginosine and its stereoisomers in high yields.,10.1021/jo702141b,2008-01-08,0.5997509925879613
Journal of Organic Chemistry,Total Synthesis of (−)-Peniphenone A,"Negishi cross-coupling between a chiral organozinc species and an aryl bromide to construct the challenging α-chiral β-aryl carbonyl motif present in the natural product. Access to the spiroketal possessing the correct stereochemistry was facilitated by an unusual thermodynamic resolution at C10. The synthesis was achieved in 14 steps (longest linear sequence) from commercially available 2,4-dihydroxybenzaldehyde in 6% overall yield. Investigations into a parallel approach required extension of Krische's enantioselective hydrogen-mediated C-C coupling to α-substituted alcohols and oxetane ring-opening with an aryllithium for assembly of the polyketide domain. These studies provide a useful foundation for further work toward the natural product family, members of which demonstrate significant activity against M. tuberculosis and offer continuing inspiration for the development of efficient new chemical methods.",10.1021/acs.joc.7b03231,2018-02-26,0.5997434864947384
Tetrahedron,"Asymmetric synthesis of (−)-epi-blastmycinone and (2R,3S,4S)-3-hydroxy-4-methyl-2-(1′-n-tetradecyl)-butanolide via a tungsten-mediated cyclization reaction",,10.1016/s0040-4039(01)00189-7,2001-03-01,0.5997428262400288
Journal of Organic Chemistry,Asymmetric Synthesis of Calyculin C. 2. Synthesis of the C<sub>26</sub>−C<sub>37</sub> Fragment and Model Wittig Couplings,We report our synthesis of the C(26)-C(37) fragment of serine/threonine protein phosphatase PP1 and PP2A inhibitor calyculin C (1). Outlined in this paper are synthetic approaches to the two components based on disconnection at the C(33)-N(3) amide bond. We report the successful synthesis of the C(33)-C(37) aza-sugar derived from D-lyxose which was coupled onto a C(26)-C(32) aminooxazole originating from L-pyroglutamic acid. Elaboration of the resulting amide to a fully deprotected C(26)-C(37) fragment of calyculin C completed our synthesis. This provided an appropriate phosphonium salt for use in a Wittig olefination for joining both halves of the natural product.,10.1021/jo960315q,1996-01-01,0.5997402069502521
Journal of Organic Chemistry,Three-Step Synthesis of (±)-Preussin from Decanal,"A straightforward and stereoselective synthesis of the alkaloid preussin is described starting from decanal and diethyl 3-diazo-2-oxopropylphosphonate. The key steps are an aza-Michael reaction from an α,β-unsaturated diazoketone followed by a highly stereoselective Cu-catalyzed ylide formation and then a [1,2]-Stevens rearrangement. This strategy is feasible for extension to preussin analogues, demonstrating its utility for the rapid construction of all-cis-substituted pyrrolidines.",10.1021/jo5011558,2014-06-30,0.5997374762961521
Synthesis,The Use of a Lactonized Statin Side-Chain Precursor in a Concise and Efficient Assembly of Pitavastatin,"A concise and simple synthetic route to pitavastatin is described. The approach involves a highly stereoselective Wittig olefination reaction between a lactonized statin side-chain precursor and the triphenylphosphonium bromide salt of the corresponding quinoline heterocyclic core. The necessary O - tert -butyl(dimethyl)silyl-protected pitavastatin lactone was obtained in 75% yield and high purity by simple crystallization from aqueous methanol. Subsequent deprotection, hydrolysis, and cation exchange in a one-pot operation provided pitavastatin calcium in 93% yield.",10.1055/s-0031-1290916,2012-04-26,0.5997338114467989
Tetrahedron,An efficient synthesis of optically active metabolites of platelet adhesion inhibitor OPC-29030 by lipase-catalyzed enantioselective transesterification,,10.1016/s0040-4039(99)00946-6,1999-07-01,0.5997312113322502
Journal of Organic Chemistry,An Enantioselective Synthesis of (+)-Polyoxamic Acid via Phase-Transfer Catalytic Conjugate Addition and Asymmetric Dihydroxylation,"A new enantioselective synthetic method of (+)-polyoxamic acid is reported. (+)-Polyoxamic acid could be obtained in 7 steps with 46% overall yield from diphenylmethyl-glycineimine tert-butyl ester via an enantioselective phase-transfer conjugate addition (99% yield, 96% ee) and an asymmetric dihydroxylation (98% yield, 94% de) as the key reactions.",10.1021/jo102272h,2010-12-30,0.5997289723427613
Synlett,"Synthetic Studies Towards the Synthesis of 6-Substituted 3-Fluoro-5,6-dihydropyran-2-ones","The synthesis of 6-substituted 3-fluoro-5,6-dihydropyran-2-ones under mild conditions is described. The key step of the synthesis involves a Julia–Kocienski olefination.",10.1055/s-0036-1588534,2017-08-17,0.5997251722785276
Organic Letters,"A General Diastereoselective Strategy for Both <i>cis</i>- and <i>trans</i>-2,6-Disubstituted Tetrahydropyrans: Formal Total Synthesis of (+)-Muconin","A protocol for general diastereoselective tandem dihydroxylation followed by S N 2 cyclization was developed for the convenient and efficient synthesis of cis - and trans -2,6-disubstituted tetrahydropyrans from ζ-mesyloxy α,β-unsaturated esters. The application of this novel method was demonstrated through the concise formal synthesis of (+)-muconin, a nonclassical acetogenin, with sequential THP–THF ring formation.",10.1021/acs.orglett.8b03053,2018-10-24,0.5997203241666682
Synlett,Synthesis of Chiral γ-Amino-β-hydroxyphosphonate Derivatives from Unsaturated Phosphonates,"γ-Amino-β-hydroxyphosphonates, useful intermediates for the synthesis of phosphonic acid analogues of carnitine, were prepared as their protected derivatives in an enantioselective manner from β,γ-unsaturated phosphonates through asymmetric ­dihydroxylation and subsequent regioselective amination via the cyclic sulfates.",10.1055/s-2004-834792,2004-10-20,0.5997173854939998
Tetrahedron,"A novel synthesis of the 1β-methylcarbapenem key intermediate employing the [2+2]-cycloaddition reaction of chlorosulfonyl isocyanate with a 4H-1,3-dioxin derivative",,10.1016/s0040-4039(01)93817-1,1989-01-01,0.5997113476022675
Organic Letters,"Asymmetric, Organocatalytic, Three-Step Synthesis of α-Hydroxy-(<i>E</i>)-β,γ-unsaturated Esters","An efficient and enantiocontrolled three-step synthesis of alpha-hydroxy-(E)-beta,gamma-unsaturated esters is reported. Enantioenriched alpha-selenyl aldehydes, prepared in one step by asymmetric, organocatalytic alpha-selenylation of aldehydes, were directly subjected to a Wittig reaction followed by allylic selenide to selenoxide oxidation and final spontaneous [2,3]-sigmatropic rearrangement to yield the target compounds in 43-65% overall yield and in 94-97% ee.",10.1021/ol100615j,2010-04-08,0.5997109936683933
Chemical Science,A chemical synthesis of 11-methoxy mitragynine pseudoindoxyl featuring the interrupted Ugi reaction,"A synthesis of 11-methoxy mitragynine pseudoindoxyl, a new member of the mitragynine class of opioid agonists, from a derivative of the Geissman-Waiss lactone is described. An internal attack of an electron-rich aromatic ring on an electrophilic nitrilium ion and a late-stage construction of the functionalized piperidine ring by the method of reductive cyclization are the pivotal transformations; both ring annulations proceed in a highly diastereoselective fashion. The construction of substituted indoxyl frameworks by the interrupted Ugi method offers an attractive alternative to the strategy of oxidatively rearranging indoles.",10.1039/c2sc20669b,2012-01-01,0.5997029131604898
European Journal of Organic Chemistry,Synthesis of the Revised Structure of Acortatarin A,"Abstract A novel Maillard‐type condensation between a primary amine derived from D ‐mannitol and a dihydropyranone, was used as a key step to access the unusual morpholine‐spiroketal acortatarin A. The synthetic approach also enabled access to a C‐2 analogue of acortatarin A, and can be used for the synthesis of related 2‐formylpyrrole natural products.",10.1002/ejoc.201403000,2014-08-25,0.5997020371255537
Tetrahedron,A practical procedure for the selective N-alkylation of 4-alkoxy-2-pyridones and its use in a sulfone-mediated synthesis of N-methyl-4-methoxy-2-pyridone,,10.1016/j.tetlet.2005.09.095,2005-10-05,0.5996951021295907
Synlett,Concise Total Synthesis of Elliptoxanthone A by Utilizing Aromatic Oxy-Cope Rearrangement for Efficient C-Isoprenylation of Xanthone Skeleton,"The first total synthesis of elliptoxanthone A, a naturally occurring isoprenylated xanthone, has been accomplished in 28% overall yield in 12 steps from commercially available 3′,4′-difluoroacetophenone by utilizing the novel C-isoprenylation of xanthone skeleton via the anion-accelerated aromatic oxy-Cope rearrangement.",10.1055/s-0035-1561476,2016-06-22,0.5996929678288502
Organic Letters,Novel Approach for the Stereocontrolled Construction of Eudesmane Skeleton:  A Concise Synthesis of (±)-Balanitol,"[structure: see text] A novel method for the stereocontrolled construction of the eudesmane ring system based on a cationic cyclization is presented, and the approach is exemplified in a short and efficient total synthesis of (+/-)-balanitol (2).",10.1021/ol016230f,2001-07-11,0.5996920467102663
Tetrahedron,"Phosphonodithioformates as heterodienophiles: synthesis of (3,6-dihydro-2H-thiopyran-2-yl)phosphonates",,10.1016/s0040-4039(00)01221-1,2000-09-01,0.5996893418501044
Journal of the American Chemical Society,Convergent Total Synthesis of Erchinines A and B and Their C20 Epimers,"The total synthesis of two monoterpenoid indole alkaloids (MIAs), erchinines A and B, is described. Isolated from the plant Ervatamia chinensis, both compounds display antimicrobial activity against Trichophyton rubrum and Bacillus subtilis . Their structures are composed of a unique caged system, bearing a 1,4-diazepine fused oxazolidine moiety and containing three successive N, O -acetals. Key features of the synthesis include the construction of the 2-aza-3-oxobicyclo[2.2.2]octene core via an intramolecular pyridone Diels–Alder reaction and a Zr-mediated bisamide reduction that induces a tandem N, O -acetal forming cascade reaction.",10.1021/jacs.5c07636,2025-07-18,0.5996892861030444
Tetrahedron,"Chiral, densely functionalized cycloheptanes from carbohydrates. I. The nitrone route",,10.1016/s0040-4039(99)00769-8,1999-06-01,0.5996792573468557
Tetrahedron,"A convenient synthesis of 2-methoxy-1-naphthyl sulfoxides in high enantiomeric purity. A new asymmetric synthesis of 1-benzyl-1,2,3,4-tetrahydroisoquinolines",,10.1016/s0040-4039(00)75860-6,1994-01-01,0.5996716762064406
Organic Letters,A Concise Total Synthesis of (±)-Minfiensine,"A concise total synthesis of (±)-minfiensine using all conventional methods and starting from commercial materials has been completed. The synthesis features a Fischer indole synthesis, a Heck alkylation of an intermediate ketone enolate, conversion of a ketone carbonyl into an epoxide, and transformation of the latter into an allylic alcohol.",10.1021/ol2027224,2011-11-11,0.599659225391359
Journal of Organic Chemistry,Synthesis of Dimethyl Gloiosiphone A by Way of Palladium-Catalyzed Domino Cyclization,"The synthesis of a spiro[4.4]nonane skeleton by the palladium-catalyzed domino cyclization of a linear 7-methylene-2,10-undecadienyl acetate is described. The pi-allylpalladium intermediate underwent intramolecular alkene insertion with high intraannular diastereoselectivity, followed by intramolecular Heck-type cyclization, leading to a spiro[4.4]nonane system. Oxidation of the allylic ether moiety and transformation of the vinyl group to an exo-methylene unit provided 3, which is the known synthetic intermediate of dimethyl gloiosiphone A (2).",10.1021/jo062546v,2007-04-12,0.5996540392086899
Organic Letters,"Studies toward the Total Synthesis of Gymnocin A, a Cytotoxic Polyether:  A Highly Convergent Entry to the F−N Ring Fragment","[structure: see text] An efficient and highly convergent synthesis of the FGHIJKLMN ring fragment of gymnocin A, a cyctotoxic polycyclic ether isolated from the notorious red-tide forming dinoflagellate Gymnodinium mikimotoi, has been achieved. The present synthesis relied on extensive use of the B-alkyl Suzuki-Miyaura coupling reaction.",10.1021/ol025814u,2002-04-18,0.5996444124506268
Tetrahedron,A diastereoselective synthesis of 4-azidotetrahydropyrans via the Prins-cyclization,,10.1016/j.tetlet.2007.07.195,2007-08-03,0.5996443791004007
Synlett,Synthesis of Panal Terpenoid Core,"Panal is a natural bicyclic cadalane-type sesquiterpenoid with an unusual combination of stereocenters. It was isolated in 1988 as an alleged biosynthetic precursor of luciferin (a light-emitting molecule) in a bioluminescent fungus Panellus stipticus . Herein we present the first approach to the synthesis of the terpenoid skeleton of panal, which includes construction of five stereocenters, one of which is easily epimerizable. The key steps in the synthetic approach presented are high-pressure Diels–Alder reaction disobeying the ‘ endo rule’, Barbier reductive allylation, and cyclization of trans -decalin ring via ring-closing metathesis.",10.1055/s-0036-1588104,2016-11-17,0.5996351362602886
Journal of Organic Chemistry,A New Approach to the Synthesis of Piperazinomycin and Bouvardin:  Facile Access to Cycloisodityrosine <i>via</i> an Intramolecular S<sub>N</sub>Ar Reaction,"A new method for the synthesis of cycloisodityrosine atropisomers I (R1 = CO2Me, R2 = NHBoc), a 14-membered m,p-cyclophane, is reported. The synthesis hinged on an efficient macrocyclization procedure for biaryl ether formation based on an intramol. SNAr reaction. The cyclization conditions are much milder and the yield is much higher than those previously reported. Moreover, the presence of the NO2 function in I provides an opportunity to introduce not only the hydroxyl group found in natural products but also others such as amino acid amide for bioactivity evaluation. 3-Fluoro-4-nitrophenylalanine II was prepd. by alkylation of a chiral bislactim ether with 3-fluoro-4-nitrobenzyl bromide; secondary amine III resulting from the double alkylation was isolated as a minor product and characterized. A mechanism was proposed for its formation. [on SciFinder (R)]",10.1021/jo951375j,1996-01-01,0.5996340420262963
Tetrahedron,A 9-step enantiospecific synthesis of (-)-aristeromycin from D-ribonic acid γ-lactone,,10.1016/s0040-4039(00)99488-7,1989-01-01,0.5996340102501179
Journal of Organic Chemistry,Synthesis of the Benzophenone Fragment of Balanol via an Intramolecular Cyclization Event,"Studies are reported on the use of either a 7-exo radical cyclization or an intramolecular Heck reaction as the key step for the construction of the benzophenone fragment of the PKC inhibitor, balanol. Whereas, the former approach was unsuccessful, the Heck reaction proved to be viable for the coupling of two fully functionalized aryl subunits affording regioselectively a biaryl seven-membered lactone with an exocyclic alkene as the major component, in contrast to the competing eight-membered ring lactone. Hydrolysis of the lactone followed by oxidative cleavage of the alkene with ruthenium tetraoxide completed this short synthesis of the benzophenone unit.",10.1021/jo000750r,2000-08-19,0.5996333654157016
Synlett,β-Amino Amides from β-Lactams: Application to the Formal Synthesis of a Peptide-Deformylase Inhibitor,"A facile and a practical synthesis of peptide-deformylase inhibitor 1 is described using an acid-catalyzed aminolysis of β-lactam 12 with pyrrolidine 6 as the key transformation. In addition, simplified conditions for the conversion of a β-hydroxy acid to a β-lactam are reported.",10.1055/s-2006-951499,2006-10-25,0.5996136788749987
Organic Letters,Total Synthesis of (+)-Pancratistatin by the Rh(III)-Catalyzed Addition of a Densely Functionalized Benzamide to a Sugar-Derived Nitroalkene,"Herein, we report the concise total synthesis of (+)-pancratistatin, accessed in a 10-step linear sequence from commercially available inputs. The convergent synthesis features a highly diastereoselective Rh(III)-catalyzed C-H bond addition to a d-glucose-derived nitroalkene and a late-stage intramolecular transamidation to furnish the B ring lactam.",10.1021/acs.orglett.7b01220,2017-05-24,0.5996132432669957
Synlett,Glucopyranose Spirohydantoins: Specific Inhibitors of Glycogen Phosphorylase,"All articles of this category A short synthesis of the spirohydantoin of glucopyranose 1β [a potent and specific inhibitor of glycogen phosphorylase], together with its inactive anomer 1α , from a readily available heptonolactone is described; this is the first synthesis of a spirohydantoin of a pyranose in which the pyranose ring is formed after the hydantoin ring. hydantocidin - glycogen phosphorylase - enzyme inhibition - hydantoin - lactone",10.1055/s-1997-940277,1997-06-01,0.5995993636372763
Journal of the American Chemical Society,A total synthesis of racemic paulownin using a type II photocyclization reaction,The lignan paulownin was prepared in a seven-step route from piperonal. The key step was a type I1 photocyclization reaction wherein two of the four stereogenic centers were introduced.,10.1021/ja00165a033,1990-04-01,0.5995947446190312
Tetrahedron,"A new route to 3a,8a-dihydrofuroc[2,3-b]benzofurans",,10.1016/s0040-4039(01)82478-3,1974-01-01,0.59959329807919
Journal of Organic Chemistry,Synthesis and Scalable Conversion of <scp>l</scp>-Iduronamides to Heparin-Related Di- and Tetrasaccharides,"A diastereomerically pure cyanohydrin, preparable on kilogram scale, is efficiently converted in one step into a novel L-iduronamide. A new regioselective acylation of this iduronamide and a new mild amide hydrolysis method mediated by amyl nitrite enables short, scalable syntheses of an L-iduronate diacetate C-4 acceptor, and also L-iduronate C-4 acceptor thioglycosides. Efficient conversions of these to a range of heparin-related gluco-ido disaccharide building blocks (various C-4 protection options) including efficient multigram access to key heparin-building block ido-thioglycoside donors are described. A 1-OAc disaccharide is converted into a heparin-related tetrasaccharide, via divergence to both acceptor and donor disaccharides. X-ray and NMR data of the 1,2-diacetyl iduronate methyl ester and the analogous iduronamide show that while both adopt (1)C(4) conformations in solution, the iduronate ester adopts the (4)C(1) conformation in solid state. An X-ray structure is also reported for the novel, (4)C(1)-conformationally locked bicyclic 1,6-anhydro iduronate lactone along with an X-ray structures of a novel distorted (4)C(1) iduronate 4,6-lactone. Deuterium labeling also provides mechanistic insight into the formation of lactone products during the novel amyl nitrite-mediated hydrolysis of iduronamide into the parent iduronic acid functionality.",10.1021/jo300722y,2012-08-17,0.5995892355052327
Organic Letters,Biogenetically Inspired Synthesis of Lingzhiol,A concise stereo- and enantioselective synthesis of lingzhiol has been achieved featuring a biogenetically inspired Brønsted acid catalyzed semipinacol rearrangement of a glycidyl alcohol intermediate.,10.1021/acs.orglett.5b03212,2016-03-14,0.5995808887593019
Tetrahedron,"A new method for the ring isomerization of isoflavones. Direct synthesis of tectorigenin, 4′-methyl-tectorigenin, caviunin and other isoflavones.",,10.1016/s0040-4039(00)71084-7,1965-01-01,0.599578640090264
Journal of Organic Chemistry,Total Syntheses of (+)- and (−)-Pestalotiopsin A,"An enantioselective total synthesis of both enantiomers of caryophyllene-type sesquiterpenoid pestalotiopsin A has been achieved, thereby establishing the absolute stereochemistry of natural (+)-pestalotiopsin A. Highlights of the synthesis include a [2 + 2] cycloaddition of N-propioloyl Oppolzer's camphorsultam and ketene dialkyl acetal and subsequent highly stereoselective 1,4-hydride addition/protonation, an aldol reaction of functionalized bicyclic lactone with aldehyde, an efficient intramolecular Nozaki-Hiyama-Kishi (NHK) reaction for the construction of the highly strained (E)-cyclononene ring, and a palladium-catalyzed reduction of allylic mesylate with retention of the E configuration.",10.1021/jo9012546,2009-08-06,0.599566699574546
Synlett,"Asymmetric Palladium(0) Catalyzed Tandem Alkylation and S<sub>N</sub>′ Cyclization of 1,4-Dichlorobut-2-ene by Chiral Imines of Aminoacetonitrile for the Total Synthesis of 1-Aminocyclopropanecarboxylic Acids","All articles of this category Chiral imines (-)- and (+)- 8a , prepared from aminoacetonitrile and (-)- or (+)-1-hydroxypinanones, reacted with E - and Z -1,4-dichlorobut-2-enes 1 in the presence of ( S )- or ( R )-BINAP palladium(0) complexes to produce the diastereoselectively pure 1-amino-2-vinylcyclopropane carbonitrile E - 13a , suitable precursor of ACCs. However subsequent Pd(0) induced reversible ring opening of the vinylcyclopropane moiety seems responsible for the low enantiomeric excesses obtained (≤32% ee). (-)- and (+)-1-hydroxypinanone aminoacetonitrile imines - E -1-amino-2-vinylcyclopropanecarbonitriles",10.1055/s-1998-1687,1998-05-01,0.5995577971630756
Organic Process Research & Development,"Process Development and Scale-Up of AZD7545, a PDK Inhibitor","A brief comparison of the early manufacturing routes to AZD7545 is given. Process development of the preferred long-term manufacturing route is reported in detail, and changes from the initial kilogram-scale route are discussed. Scale-up experience from the pilot-plant manufacture is included in the discussion of each stage. Noteworthy aspects throughout the development of AZD7545 concerned chemical hazards, mechanisms, analysis, and impurities, upon which this case study will focus.",10.1021/op2003419,2012-02-03,0.5995551391126422
Journal of the American Chemical Society,"Zr-Catalyzed Kinetic Resolution of Allylic Ethers and Mo-Catalyzed Chromene Formation in Synthesis. Enantioselective Total Synthesis of the Antihypertensive Agent (<i>S</i>,<i>R</i>,<i>R</i>,<i>R</i>)-Nebivolol","The first enantioselective total synthesis of the antihypertensive agent ( S, R, R, R )-nebivolol ( 3 ) is described. The synthesis includes the efficient (EBTHI)Zr-catalyzed kinetic resolutions of cycloheptenyl styrenyl ethers 8 and 16, which are subsequently treated with 4 mol % Mo(CHCMe 2 Ph)(N(2,6-( i -Pr) 2 C 6 H 3 ))(OCMe(CF 3 ) 2 ) 2 to afford chiral nonracemic 2-substituted chromenes ( R, R )- 9 and ( S, R )- 17 . Since the present retrosynthetic analysis dissects the molecule into two chromene fragments, both the ( R ) and ( S ) antipodes of (EBTHI)Zr catalyst are required. Accordingly, Buchwald's efficient resolution process is used to resolve rac -(EBTHI)ZrCl 2 (from catalytic hydrogenation of commercially available rac -(EBI)ZrCl 2 ), such that the two requisite transition metal chiral catalysts are obtained by a single process. Other noteworthy features of the synthesis include a highly efficient, regio- and stereoselective Pd-catalyzed opening of cyclic allylic epoxide 7 with diaryloxystannane 15 and a photochemical modification of the C2 chromane side chain (e.g., 10 → 11 ).",10.1021/ja981378o,1998-08-01,0.5995530346589127
Organic Letters,"First Total Synthesis of Cassiarin A, a Naturally Occurring Potent Antiplasmodial Alkaloid","The first total synthesis of cassiarin A, an antiplasmodial alkaloid isolated from Cassia siamea, was achieved via sequential alkynylation of arenes with Sonogashira coupling and 6- endo-dig-cyclization of phenolic oxygens to the resulting alkynes.",10.1021/ol8004112,2008-04-16,0.599551456989131
Journal of Organic Chemistry,Total Synthesis of Epothilones B and D: Stannane Equivalents for β-Keto Ester Dianions,"Studies leading to a total synthesis of epothilones B and D are described. The overall synthetic plan was based on late-stage fragment assembly of two segments representing C(1)-C(9) and C(10)-C(21) of the structure. The C(1)-C(9) fragment was prepared by elaboration of commercially available (2R)-3-hydroxy-2-methylpropanoate at both ends of the three-carbon unit. Introduction of carbons 1-4 containing the gem-dimethyl unit was achieved in a convergent manner using a diastereoselective addition of a stannane equivalent of a beta-keto ester dianion. An enantioselective addition of such a stannane equivalent for a beta-keto ester dianion was also used to fashion one version of the C(10)-C(21) subunit; however, the fragment assembly (using bimolecular esterification followed by ring-closing metathesis) with this subunit failed. Therefore, fragment assembly was achieved using a Wittig reaction; this was followed by macrolactonization to close the macrocycle. The C(10)-C(21) subunit needed for this approach was prepared in an efficient manner using the Corey-Kim reaction as a key element. Other key reactions in the synthesis include a stereoselective SmI(2) reduction of a beta-hydroxy ketone and a critical opening of a valerolactone with aniline which required extensive investigation.",10.1021/jo802215v,2008-11-08,0.5995370618974099
Journal of Organic Chemistry,Total Synthesis of Strasseriolide A,"Stereoselective total synthesis of structurally intriguing antimalarial macrolide strasseriolide A has been accomplished by adopting a convergent approach. The salient features of this synthesis include Co(BH 4 ) 2 -mediated selective reduction of conjugated olefin, Crimmins propionate aldol, Evans alkylation, intermolecular Horner–Wadsworth–Emmons olefination, Yamaguchi macrolactonization, and selective saponification of ester moiety in the presence of a lactone functionality. The 13 C{ 1 H} NMR data of strasseriolide A were found to be very sensitive to its solution concentration.",10.1021/acs.joc.2c01595,2022-08-12,0.5995370126658526
Journal of the American Chemical Society,Total Synthesis of Rameswaralide Utilizing a Pharmacophore-Directed Retrosynthetic Strategy,"A pharmacophore-directed retrosynthetic strategy was applied to the first total synthesis of the cembranoid rameswaralide in order to simultaneously achieve a total synthesis while also developing a structure–activity relationship profile throughout the synthetic effort. The synthesis utilized a Diels–Alder lactonization process, including a rare kinetic resolution to demonstrate the potential of this strategy for an enantioselective synthesis providing both the 5,5,6- and, through a ring expansion, 5,5,7-tricyclic ring systems present in several Sinularia soft coral cembranoids. A pivotal synthetic intermediate, a tricyclic epoxy α-bromo cycloheptenone, displayed high cytotoxicity with interesting selectivity toward the HCT-116 colon cancer cell line. This intermediate enabled the pursuit of three unique D-ring annulation strategies including a photocatalyzed intramolecular Giese-type radical cyclization and a diastereoselective, intramolecular enamine-mediated Michael addition, with the latter annulation constructing the final D-ring to deliver rameswaralide. The serendipitous discovery of an oxidation state transposition of the tricyclic epoxy cycloheptenone proceeding through a presumed doubly vinylogous, E1-type elimination enabled the facile introduction of the required α-methylene butyrolactone. Preliminary biological tests of rameswaralide and precursors demonstrated weak cytotoxicity; however, the comparable cytotoxicity of a simple 6,7-bicyclic β-keto ester, corresponding to the CD-ring system of rameswaralide, to that of the natural product itself suggests that such bicyclic β-ketoesters may constitute an interesting pharmacophore that warrants further exploration.",10.1021/jacs.2c08245,2022-09-27,0.5995369822665643
Tetrahedron,"The isolation, structural determination, and total synthesis of terfestatin A, a novel auxin signaling inhibitor from Streptomyces sp.",,10.1016/j.tetlet.2004.09.055,2004-09-25,0.5995323344678706
Synthesis,Asymmetric Routes Towards Polyfunctionalized Pyrrolidines: A Short Diastereoselective Synthesis of Polyhydroxylated Pyrrolidines and an Indolizidine,"All articles of this category Various (2 S ,3 S ,4 R )-2-[(1 R )-1-hydroxyalkyl]pyrrolidine-3,4-diols ( 11 ) have been prepared in 8 steps and 13-20% overall yields starting from ( R )-(-)-phenylglycinol. This concise approach is based on the condensation of a chiral silyloxypyrrole with aldehydes which gave the ( R , R )-aldol compounds in good yields and high diastereoselectivities. The cis -hydroxylation followed by reduction and deprotection gave the desired trihydroxylated pyrrolidines. The same strategy has been successively applied to a formal synthesis of 8a- epi -swainsonine. aldol condensation - OsO 4 hydroxylation - polyhydroxy pyrrolidines and indolizidine - 8- epi -swainsonine",10.1055/s-1999-3434,1999-04-01,0.5995317980798696
Synthesis,A Facile and Improved Synthesis of Cyanoguanidines from Carbodiimides,,10.1055/s-1980-29203,1980-01-01,0.5995286168877297
Journal of Organic Chemistry,Formal Synthesis of <i>ent</i>-Cephalotaxine Using a One-Pot Parham–Aldol Sequence,"A short formal synthesis of ent-Cephalotaxine is achieved. The approach features a new Lewis acid-mediated [2,3]-Stevens rearrangement of N-allylated prolineamide to generate a key quaternary stereogenic center. Additionally, a one-pot Parham-aldol sequence was developed to rapidly assemble two of the four rings in the cephalotaxine core.",10.1021/acs.joc.8b01540,2018-07-17,0.5995145839505741
European Journal of Organic Chemistry,"Synthesis of a New 2,3‐Diaminoconduritol with Conduritol F Structure","Abstract A new 2,3‐diaminoconduritol derivative with the conduritol F structure was prepared starting from cyclohexa‐1,4‐diene. Initially, a lactam, prepared by the cycloaddition of chlorosulfonyl isocyanate (CSI) to cyclohexa‐1,4‐diene, was converted into an amino acid. The conversion of the acid functionality into an isocyanate resulted in the formation of an imidazolidinone derivative, formed by an intramolecular cyclization. In the second part of this work, the known anhydride, 3a,4,7,7a‐tetrahydroisobenzofuran‐1,3‐dione was successfully converted into the desired bis(carbamate). The bromination of the double bond in the six‐membered ring followed by a DBU‐induced (DBU = 1,8‐diazabicyclo[5.4.0]undec‐7‐ene) HBr elimination furnished the symmetrical diene. The photooxygenation of the diene unit afforded the bicyclic endoperoxide. The reaction of the endoperoxide with thiourea followed by acetylation resulted in the formation of a syn ‐configured diacetate. The deprotection of the urethane and acetate groups gave the new 2,3‐diaminoconduritol with the conduritol F structure.",10.1002/ejoc.201200582,2012-07-25,0.5995078418602577
Journal of the American Chemical Society,"Total Synthesis of the Sesquiterpenoid Polyols (±)-Euonyminol and (±)-3,4-Dideoxymaytol, Core Constituents of Esters of the<i>Celastraceae</i>","A general synthetic route to the set of polyhydroxylated agarofurans that comprise the core structures of esters present in plants of the Celastraceae family has been devised. The pathway is exemplified with total syntheses of (±)-3,4-dideoxymaytol ( 3 ), the nucleus of ever-1 ( 6 ), and (±)-euonyminol ( 4 ), the sesquiterpenoid core of several cathedulins including K-19 ( 5 ). A focal intermediate 19, prepared by Diels−Alder addition of 11 to 12, was identified that permitted stereoselective introduction of an isopropenyl substituent via chelation-controlled, conjugate Grignard addition to give 34 . Triflic acid-catalyzed cyclization of 39 afforded the agarofuran skeleton of 3, and subsequent epimerization of the hydroxyl substituent at C1 via a reversible aldol sequence gave 41 . Sequential reductions using hydride and catalytic hydrogenation yielded 3 and 4- epi -3,4-dideoxymaytol ( 51 ). The route from 19 was extended toward 4 via 56, prepared by directed epoxidation of 34 . A trifuoroacetic acid-catalyzed “epoxide-cascade” cyclization of 56 furnished 61, which was advanced to γ-lactone 63 prior to epimerization at C1. Introduction of the 8β hydroxyl function of 69 was followed by an α-ketol transposition to give 71 which was reduced and protected as polysilyl ether 80 . Osmylation and replacement of protecting groups produced euonyminol octaacetate 78 which underwent methanolysis to (±)- 4 .",10.1021/ja963567h,1997-03-01,0.5994984447993096
European Journal of Organic Chemistry,Protecting Group Free Formal Total Synthesis of the Antitubercular Agent Erogorgiaene,"Abstract The formal total synthesis of the antitubercular agent erogorgiaene was achieved in 12 steps by using a protecting group free strategy. The synthesis involves an enamine‐mediated 1,4‐addition, an aldol condensation, dehydrogenation, Wittig olefination, intramolecular Friedel–Crafts cyclization, TEMPO‐BAIB‐mediated oxidation, and Evans auxiliary based diastereoselective methylation.",10.1002/ejoc.201101269,2011-11-03,0.599495250756832
Journal of Organic Chemistry,Stereoselective Palladium-Catalyzed α-Arylation of 3-Aryl-1-Indanones: An Asymmetric Synthesis of (+)-Pauciflorol F,"Highly stereoselective, palladium-catalyzed α-arylation reactions of 3-aryl-1-indanones with aryl bromides are described. The use of sodium tert-butoxide as a base in this process is required to elevate the efficiencies and stereoselectivities of these reactions. The new methodology was successfully applied to a highly efficient route for the asymmetric synthesis of (+)-pauciflorol F.",10.1021/jo2009164,2011-07-11,0.5994949962520737
Tetrahedron,"Synthesis of a novel α-glucoside of the powerful glucosidase inhibitor 2,5-dideoxy-2,5-imino-d-mannitol via enzymatic glucosylation of 5-azido-5-deoxy-d-fructopyranose",,10.1016/s0040-4039(96)02281-2,1997-01-01,0.5994933635212325
Synlett,"Resolution of 2-Silyloxy-1-oxiranyl-4-pentenes by HKR: Total Synthesis of (5<i>S</i>,7<i>R</i>)-Kurzilactone","Enantiomerically pure syn- and anti-2-silyloxy-1-oxiranyl-4-pentenes were prepared by using Jacobsen’s hydrolytic kinetic resolution (HKR) method. A resolved epoxypentenol generated in this fashion was used in the total synthesis of (5S,7R)-kurzilactone by a pathway employing epoxide ring-opening and RCM reactions in key steps.",10.1055/s-2005-922774,2005-12-20,0.5994918985788421
Organic Letters,Convergent Synthesis of Kibdelone C,"The synthesis of kibdelone C, a polycyclic natural xanthone isolated from a soil actinomycete, was achieved through a convergent approach. A 6π-electrocyclization was applied to construct the highly substituted dihydrophenanthrenol fragment (B–C–D ring). InBr 3 -promoted lactonization was employed to build the isocoumarin ring, which served as a common precursor for the formation of isoquinolinone ring (A–B ring). A key DMAP-mediated oxa -Michael/aldol cascade reaction was developed to install the tetrahydroxanthone fragment (E–F ring). This approach provides a new solution to prepare its derivatives and structurally related natural products.",10.1021/acs.orglett.8b00901,2018-05-08,0.5994882843228131
Organic Letters,"Synthesis of Immunostimulatory α-<i>C</i>-Galactosylceramide Glycolipids via Sonogashira Coupling, Asymmetric Epoxidation, and Trichloroacetimidate-Mediated Epoxide Opening","Stereocontrolled syntheses of alpha-C-GalCer (2) and its alpha-C-acetylenic analogue 6 were accomplished in high efficiency by a convergent construction strategy from 1-hexadecene and d-galactose. The key transformations include Sonogashira coupling, Sharpless asymmetric epoxidation, and Et(2)AlCl-catalyzed cyclization of an epoxytrichloroacetimidate to generate protected dihydrooxazine 21.",10.1021/ol1009976,2010-06-02,0.5994833309092077
Journal of the American Chemical Society,The First Synthesis of Herbicidin B. Stereoselective Construction of the Tricyclic Undecose Moiety by a Conformational Restriction Strategy Using Steric Repulsion between Adjacent Bulky Silyl Protecting Groups on a Pyranose Ring,"The first total synthesis of the nucleoside antibiotic herbicidin B ( 1b ) was achieved, where a novel aldol-type C -glycosidation reaction promoted by samarium diiodide (SmI 2 ) was used as a key step. Treatment of methyl 3,4- O -(1,1,3,3-tetraisopropyl-1,3-disiloxanediyl)-1-phenylthio-2-ulos-β- d -glucuronate ( 13 ) with SmI 2 in THF regioselectively gave the corresponding 1-enolate, which was readily trapped with 1-β- d -xylosyladenine 5‘-aldehyde derivative 7 to afford the product 19a, b as an anomeric mixture. Dehydration of the 5‘-hydroxyl in 19a, b with using Burgess's inner salt gave the enone 20, which was subsequently hydrogenated to give undeculofuranuronyl adenine derivative 21 . Deprotection of 21 gave a tricyclic sugar nucleoside, 23 . However, it was an epimer of herbicidin B at the 6‘-position. Construction of the desired 6‘-α-configuration was achieved by using a conformational restriction strategy based on repulsion between adjacent bulky protecting groups on the pyranose ring. Thus, when methyl 3- O - tert -butyldimethylsilyl-4- O - tert -butyldiphenylsilyl-1-phenylthio-2-ulos- d -glucuronate ( 29c ), the conformation of which was restricted in an unusual 1 C 4 -like conformation, was used as a precursor for ulose 1-enolate in the SmI 2 -promoted aldol reaction with 7, the desired 6‘-α-aldol product 30c was predominantly obtained. Compound 30c was dehydrated, followed by hydrogenation of the alkenyl bond and then deprotection to form an internal ketal linkage between the 3‘- and 7‘-positions, which spontaneously gave herbicidin B.",10.1021/ja992608h,1999-10-16,0.599472355225931
Tetrahedron,"An efficient synthesis of new 1-H-4′-methyl-3′,4′-dihydrospiro[piperidine-4,2′(1′H)quinoline] scaffolds",,10.1016/j.tetlet.2007.02.037,2007-02-14,0.5994703518176288
European Journal of Organic Chemistry,A Concise Synthesis of Globotriaosylsphingosine,"Abstract Globotriaosylsphingosine (lysoCTH) is produced in the cell by deacylation of the globo ‐sphingolipid globotriaosylceramide. The latter compound is the major storage material encountered in Fabry patients, an inherited lysosomal storage disorder characterized by partially impaired α‐galactosidase A (GLA) activity. Recent findings suggest that lysoCTH, next to its acylated precursor, is an important causative of Fabry disease symptoms. The glycolipid is thus a relevant synthetic target, and we here report on its efficient synthesis. Key to our strategy is the use of 4,6‐ O ‐di‐ tert ‐butylsilylene‐protected D ‐galactose donors to yield D ‐Gal‐α‐ D ‐Gal linkages with high stereoselectivity. In our optimized route we make use of acyl protecting groups to mask most of the hydroxy functions in the carbohydrate building blocks to facilitate straightforward global deprotection.",10.1002/ejoc.201001690,2011-02-11,0.5994695745998387
Organic Letters,Nodulisporic Acid A Synthetic Studies. 2. Construction of an Eastern Hemisphere Subtarget,"In this, the second of two Letters, we describe an effective assembly of (+)-4, an eastern hemisphere subtarget comprising the FGH rings of (+)-nodulisporic acid A (1) (17 steps, 9% overall yield). Central to the synthesis is a Koga three-component conjugate addition-alkylation sequence which secures the trans orientation of the vicinal quaternary methyl groups. [reaction: see text]",10.1021/ol016888t,2001-11-01,0.5994673169772278
Tetrahedron,Enantioselective synthesis of ring-C aromatic steroids by asymmetric Michael-type alkylation of chiral imines.,,10.1016/s0040-4039(00)96126-4,1987-01-01,0.5994648562373771
Organic Letters,Biomimetic Total Synthesis of (+)-Himbacine,On treatment with trifluoroacetic acid butenolide 14 undergoes N-Boc deprotection and condensation followed by an iminium ion activated intramolecular Diels-Alder cycloaddition to give the (+)-himbacine precursor 11 on reductive work up. Compound 11 was converted into (+)-himbacine in four synthetic steps. [reaction: see text],10.1021/ol047676+,2005-01-20,0.5994546194210723
Tetrahedron,"Synthesis and optical resolution of dl-cis-2-fluorocycloproplylamine, the key component of the new generation of quinolonecarboxylic acid, DU-6859",,10.1016/s0040-4039(00)92669-8,1992-06-01,0.5994507645084203
Journal of the American Chemical Society,"A Two-Directional Approach to a (−)-Dictyostatin C11−C23 Segment:  Development of a Highly Diastereoselective, Kinetically-Controlled Meerwein−Ponndorf−Verley Reduction","A three-step synthesis of a precursor to the C11-C23 segment of (-)-dictyostatin is described. The sequence features a sonication-assisted, enantioselective double hetero Diels-Alder (HDA) reaction catalyzed by Jacobsen's Cr(III) Schiff base catalyst, followed by a novel, highly diastereoselective Meerwein-Ponndorf-Verley (MPV) reduction of the hydropyranone subunits under kinetic control to yield the bis(axial alcohol) 4. Generalized studies of both the HDA and MPV methodologies are also described.",10.1021/ja077336u,2007-11-30,0.5994493284742005
Journal of Organic Chemistry,"Benzyl 2-Cyano-3,3-Dimethyl-1-pyrrolidinecarboxylate, a Versatile Intermediate for the Synthesis of 3,3-Dimethylproline Derivatives","The synthesis of racemic nitrile (+/-)-9 was accomplished in four steps and 58% overall yield from the known pyrrolidinone 5. Nitrile (+/-)-9 was resolved via preparative chiral HPLC to afford optically pure nitriles (+)-9 and (-)-9, from which 3,3-dimethylprolines (+)-1 and (-)-1 and 3,3-dimethylprolinamides (+)-2 and (-)-2 could be accessed in nearly quantitative yield, without loss of optical purity. The absolute configurations of the resolved prolines and prolinamides were determined by correlation with an intermediate of known absolute stereochemistry.",10.1021/jo7027163,2008-04-23,0.5994471916752002
Tetrahedron,"An efficient synthesis of β-acylureas via a three-component, one-pot synthesis using TCS/ZnCl2",,10.1016/j.tetlet.2011.01.066,2011-01-24,0.5994465227210013
Angewandte Chemie International Edition,A Formal Asymmetric Synthesis of (+)-Anatoxin-a Using an Enantioselective Deprotonation Strategy on an Eight-Membered Ring,"In only seven steps a formal synthesis of enantiomerically enriched (+)-anatoxin-a has been achieved. This was accomplished by utilizing a highly enantioselective desymmetrization of the eight-membered ring ketone 1 to form 2, and a novel cascade reaction to construct the 9-azabicyclo[4.2.1]nonane skeleton.",10.1002/(sici)1521-3773(19990712)38:13/14<1985::aid-anie1985>3.3.co;2-z,1999-07-12,0.5994423700155158
Angewandte Chemie International Edition,A Formal Asymmetric Synthesis of (+)-Anatoxin-a Using an Enantioselective Deprotonation Strategy on an Eight-Membered Ring,"In only seven steps a formal synthesis of enantiomerically enriched (+)-anatoxin-a has been achieved. This was accomplished by utilizing a highly enantioselective desymmetrization of the eight-membered ring ketone 1 to form 2, and a novel cascade reaction to construct the 9-azabicyclo[4.2.1]nonane skeleton.",10.1002/(sici)1521-3773(19990712)38:13/14<1985::aid-anie1985>3.0.co;2-7,1999-07-12,0.5994423700155158
Synthesis,A Synthesis of (+)-Obtusenyne,A synthesis of the halogenated medium-ring ether natural product (+)-obtusenyne is reported utilizing a Claisen rearrangement and an intramolecular hydrosilation as key steps.,10.1055/s-2005-918470,2005-01-01,0.5994287045186952
Organic Letters,Synthesis of Dihydrooxepin Models Related to the Antitumor Antibiotic MPC1001,"4-Hydroxy-L-proline was converted into the tetrahydrooxepino[4,3-b]pyrrole ring system characteristic of the potent antitumor agent MPC1001. Key steps were regioselective formation of a vinylogous amide by use of Bredereck's reagent and acid-induced cyclization of an alcohol onto the carbon-carbon double bond of that amide by addition-elimination to generate the seven-membered oxacyclic subunit.",10.1021/ol071147z,2007-06-20,0.5994271740849422
Tetrahedron,An enzymatic route to the synthesis of tricyclic fused hexahydrofuranofuran P2-Ligand for a series of highly potent HIV-1 protease inhibitors,,10.1016/j.tetlet.2024.155013,2024-03-16,0.5994239165410891
Journal of Organic Chemistry,Alternative Synthesis of P-Chiral Phosphonite-Borane Complexes: Application to the Synthesis of Phostone–Phostone Dimers,"An improved strategy for the synthesis of P-chiral gluco- and manno-phosphonite-borane complexes is described on the basis of the addition of diethyl phosphonite-borane to a glucal-derived aldehyde, followed by a cyclization coupled with an ethyl/methyl exchange. This direct P(III) strategy facilitates the obtention of various P-chiral phosphonite-boranes, of which further coupling reactions are described leading to the selective synthesis of two phostone dimers.",10.1021/jo400864s,2013-06-21,0.5994180489059343
Angewandte Chemie International Edition,Enantioselective Synthesis of the Cyclopiazonic Acid Family Using Sulfur Ylides,"A convergent, nine-step (LLS), enantioselective synthesis of α-cyclopiazonic acid and related natural products is reported. The route features a) an enantioselective aziridination of an imine with a chiral sulfur ylide; b) a bioinspired (3+2)-cycloaddition of the aziridine onto an alkene; and c) installation of the acetyltetramic acid by an unprecedented tandem carbonylative lactamization/N-O cleavage of a bromoisoxazole.",10.1002/anie.201712065,2017-12-19,0.5994126627445068
Organic Process Research & Development,Evolution of a Scale-Up Synthesis to a Potent GluN2B Inhibitor and Its Prodrug,"This paper describes the efficient scale-up synthesis of the potent negative allosteric glutamate N2B (GluN2B) inhibitor 1 (BMS-986169), which relies upon a stereospecific S N 2 alkylation strategy and a robust process for the preparation of its phosphate prodrug 28 (BMS-986163) from parent 1 using POCl 3 . A deoxyfluorination reaction employing bis(2-methoxyethyl)aminosulfur trifluoride (Deoxo-Fluor) is also used to stereospecifically introduce a fluorine substituent. The optimized routes have been demonstrated to provide APIs suitable for toxicological studies in vivo.",10.1021/acs.oprd.8b00120,2018-06-05,0.5994054979382153
Tetrahedron,New convenient synthesis of iridol. An approach to the synthesis of ubiquinones,,10.1016/j.tetlet.2005.01.001,2005-01-19,0.5994024954858677
Organic Letters,Synthesis of Plakortone B and Analogs,"[Structure: see text] Use of a palladium-mediated alkoxycarbonylation/lactonization process provides a variable route to analogs of the plakortones. Four different analogs, including natural plakortone B, have been synthesized via this route.",10.1021/ol0618656,2006-10-13,0.5994024927237629
Organic Letters,Double Cycloisomerization as a Novel and Expeditious Route to Tricyclic Heteroaromatic Compounds:  Short and Highly Diastereoselective Synthesis of (±)-Tetraponerine T6,[reaction: see text] Cu-Assisted double cycloisomerization of bis-alkynylpyrimidines afforded the 5-6-5 tricyclic heteroaromatic skeleton. This transformation was used as a key step in the highly diastereoselective total synthesis of (+/-)-tetraponerine T6.,10.1021/ol027129t,2002-12-01,0.5993672550361592
Tetrahedron,A new route to homochiral trans-disubstituted cyclopentanes,,10.1016/s0040-4039(01)80503-7,1989-01-01,0.5993595779839006
Organic Letters,A Novel Short Convergent Entry into Himbacine Derivatives,"[reaction: see text]. The IMDA reaction of 9 leads with good stereoselectivity to exo-adduct 10b. The functionalized ABC-ring core in 10 is well suited for the convergent synthesis of analogues of himbacine, a naturally occurring M2 selective muscarine receptor antagonist, as illustrated with the further synthesis of the dehydro-derivative 5.",10.1021/ol025801g,2002-04-02,0.5993589934244713
Tetrahedron,Total synthesis of a potent immunosuppressant pironetin,,10.1016/0040-4039(96)01413-x,1996-09-01,0.5993490923335473
Tetrahedron,"Total synthesis of callystatin A, a potent cytotoxic polyketide from the marine sponge, Callyspongia truncata",,10.1016/s0040-4039(98)00151-8,1998-04-01,0.5993490923335473
Tetrahedron,"Total synthesis of lyngbyabellin A, a potent cytotoxic metabolite from the marine cyanobacterium Lyngbya majuscula",,10.1016/s0040-4039(01)00678-5,2001-06-01,0.5993490923335473
Synlett,Sulfamide Synthesis via Pd-Catalysed Cross-Coupling,A novel efficient procedure for the improved synthesis of aryl-substituted sulfamides via a Pd-catalysed arylation of sulf­amide is reported.,10.1055/s-2004-836052,2004-11-29,0.599345639368771
Journal of Organic Chemistry,"A New Strategy for the Synthesis of 1,4-Benzodiazepine Derivatives Based on the Tandem <i>N-</i>Alkylation−Ring Opening−Cyclization Reactions of Methyl 1-Arylaziridine-2-carboxylates with <i>N-</i>[2-Bromomethyl(phenyl)]trifluoroacetamides","A new method for the synthesis of novel 1,4-benzodiazepine derivatives has been established from a one-pot reaction of methyl 1-arylaziridine-2-carboxylates with N-[2-bromomethyl(aryl)]trifluoroacetamides. The reaction proceeds through the N-benzylation and highly regioselective ring-opening reaction of aziridine by bromide anion followed by Et3N-mediated intramolecular nucleophilic displacement of the bromide by the amide nitrogen. The easy availability of starting materials, simple and convenient synthetic procedure, and formation of functionalized 1,4-benzodiazepine scaffold ready for further chemical manipulations render this strategy useful in synthetic and medicinal chemistry.",10.1021/jo7024306,2008-01-30,0.5993412227867294
Organic Letters,Studies toward the Synthesis of Amphidinolide C1: Stereoselective Construction of the C(1)–C(15) Segment,"An enantioselective synthesis of the C(1)-C(15) segment of the marine natural product amphidinolide C has been accomplished by a route that includes a stereoselective boron-Wittig reaction to furnish a trisubstituted alkenylboronate. In addition, the route employs enantioselective alkene diboration to install the C(6) hydroxyl group which undergoes intramolecular conjugate addition to establish a tetrahydrofuran ring. Lastly, a catalytic Suzuki-Miyaura cross-coupling is accomplished to construct the C(9)-C(10) bond.",10.1021/acs.orglett.0c03134,2020-11-12,0.5993378698510864
Angewandte Chemie International Edition,"Asymmetric Total Synthesis of Indole Diterpenes Paspalicine, Paspalinine, and Paspalinine‐13‐ene","Paspaline-derived indole diterpenes (IDTs) are structurally complex mycotoxins with unique tremorgenic activity. Reported are asymmetric total syntheses of three paspaline-derived IDTs paspalicine, paspalinine and paspalinine-13-ene. Our synthesis features a green Achmatowicz rearrangement/bicycloketalization for the efficient construction of FG rings (75 % yield) and a cascade ring-closing metathesis of dienyne for highly regioselective formation of CD rings (72 % yield). Other highlights include four palladium-mediated reactions (Stille, aza-Wacker, Suzuki, and Heck) to forge the BE rings and the installation of two continuous all-carbon quaternary stereocenters via reductive ring-opening of cyclopropane and α-methylation of the conjugate ester. Our new synthetic strategy is expected to be applicable to the chemical synthesis of other paspaline-derived IDTs and will facilitate the bioactivity studies of these agriculturally and pharmacologically important IDTs.",10.1002/anie.202115384,2021-11-16,0.5993369137084343
Organic Letters,Synthesis of a C4-<i>e</i><i>pi</i>-C1−C6 Fragment of FR901464 Using a Novel Bromolactolization,"[reaction: see text] A synthesis of a C4-epi-C1-C6 fragment of the antitumor agent FR901464 is reported. The advanced intermediate prepared in this study contains two of the three correct stereocenters found in the C1-C6 moiety of FR901464. For the preparation of this intermediate, we have developed a highly diastereoselective bromolactolization of a delta-alkenyl ketone.",10.1021/ol049160w,2004-09-18,0.5993350790014077
Tetrahedron,The total synthesis of ritipenems. Construction of penem thiazoline ring by incorporation of two 2C units of glycolic acid.,,10.1016/s0040-4039(00)79192-1,1993-05-01,0.5993333233292585
Organic Letters,A New and Efficient Method for <i>o</i>-Quinone Methide Intermediate Generation:  Application to the Biomimetic Synthesis of (±)-Alboatrin,[reaction: see text] A new and efficient method for o-quinone methide intermediate generation from o-methyleneacetoxy-phenols has been developed and applied to the biomimetic synthesis of (+/-)-Alboatrin.,10.1021/ol048479d,2004-08-26,0.599331419637989
Organic Letters,"Iodine(III)-Promoted Ring Contraction of 1,2-Dihydronaphthalenes:  A Diastereoselective Total Synthesis of (±)-Indatraline","[reaction: see text] A new approach for the synthesis of (+/-)-indatraline, which is a 3-phenyl-1-indanamine that displays several biological activities, is described. The strategy features as the key step a diastereoselective ring contraction of a 1,2-dihydronaphthalene promoted by PhI(OTs)OH, to construct the indan ring system. The oxidative rearrangement of other 1,2-dihydronaphthalenes was also investigated, generalizing this method to obtain indans.",10.1021/ol070027o,2007-03-20,0.599326211295617
Synthesis,Synthesis of Bis(ethylenedithio)tetrathiafulvalene (BEDT-TTF),"All articles of this category 2-Oxo-5,6-dihydro-1,3-dithiolo[4,5- b ][1,4]dithiin ( 4 ) was prepared in four steps from cheap starting materials in high overall yield. Coupling of 4 with trimethyl phosphite in toluene gave bis(ethylenedithio)tetrathiafulvalene ( 5 ; BEDT-TTF; 2,2′-bi-5,6-dihydro-1,3-dithiolo[4.5- b ][1,4]dithiinylidene) in 96% yield.",10.1055/s-1989-27175,1989-01-01,0.5993231435149112
Synthesis,"A Practical Synthesis of 1,4,5,8-Tetramethoxyanthracene from Inexpensive and Readily Available 1,8-Dihydroxyanthraquinone","The preparation of gram quantities of 1,4,5,8-tetra­methoxyanthracene from commercially available and inexpensive 1,8-dihydroxyanthraquinone is described. The key steps in the synthesis involve bromination of 1,8-dimethoxyanthracene to form 1,8-dibromo-4,5-dimethoxyanthracene followed by Cu(I) catalyzed replacement of bromo substituents with methoxy groups. The contrasting reports concerning the preparation of 1,8-dimethoxy­anthracene from 1,8-dimethoxyanthraquinone using zinc dust in refluxing acetic acid are also discussed.",10.1055/s-0031-1289695,2012-02-06,0.5993230834748154
Synthesis,A Seven-Step Total Synthesis of (–)-Thebaine,"Abstract The morphinan alkaloid (–)-thebaine is an industrially important chemical intermediate deployed in the semi-synthesis of various opioid medicines. Here, a seven-step total synthesis of this natural product is reported from simple, commercially available starting materials. The pivotal aryl allyl ether substrate, which is obtained through successive Suzuki-Miyaura cross-coupling and Mitsunobu substitution reactions, was engaged in a double-Heck cyclization sequence. The tetracyclic product of these processes was subjected to a photochemical hydroamination reaction that generated a N-Boc piperidine derivative embodying the full pentacyclic morphinan framework. Over a further three simple steps, this last compound was converted into (–)-thebaine.",10.1055/a-1948-3335,2022-09-21,0.5993217662525577
Organic Letters,Toward an Enantioselective Synthesis of (−)-Zampanolide: Preparation of the C9–C20 Region,"Progress toward the synthesis of the microtubule-stabilizing agent, (-)-zampanolide, is reported. Construction of the 2,6-cis-tetrahydropyran ring was accomplished utilizing ether transfer methodology in conjunction with an intramolecular radical cyclization reaction. Efficient installation of the C16-C20 side chain relied on a one-pot cross-metathesis/olefination sequence, Sharpless epoxidation, and selective reduction of a vinyl epoxide.",10.1021/ol301383a,2012-06-21,0.5993207826077807
Organic Letters,"2-Aryl-<i>N</i>-tosylazetidines as Formal 1,4-Dipoles for [4 + 2] Cycloaddition Reactions with Nitriles:  An Easy Access to the Tetrahydropyrimidine Derivatives",[reaction: see text] A new synthetic route to 2-aryl-N-tosyl azetidines has been developed starting from N-tosylarylaldimines in two steps in an overall yield of 63-70%. A formal [4 + 2] cycloaddition of these 2-aryl-N-tosylazetidines with nitriles in the presence of BF3.OEt2 has been described for the synthesis of substituted tetrahydropyrimidines. It is proposed that the reaction proceeds in Ritter fashion.,10.1021/ol048161l,2004-11-20,0.5993166956067635
Organic Letters,Synthesis of the ABC Ring System of Jiadifenin <i>via</i> Pd-Catalyzed Cyclizations,"An efficient route toward the central ABC system of jiadifenin has been developed using two key Pd-catalyzed cyclizations. A protic solvent-activated Mizoroki-Heck reaction was used to construct the C(9) quaternary carbon and the A ring. A cascading Tsuji-Trost cyclization/lactonization sequence was employed to establish the BC ring system and the C(5,6) stereochemistry.",10.1021/ol103024z,2011-01-25,0.5993155614035238
Synthesis,A Practical Synthesis of<i>N</i>-Hydroxy-α-amino Acid Derivatives,,10.1055/s-1980-29255,1980-01-01,0.5993131870936267
Organic Letters,"Divergent Synthesis of Cytotoxic Styryl Lactones Related to Goniobutenolides A and B, and to Crassalactone D","Goniobutenolides A (1) and B (2), crassalactone D (3), 4-epi-crassalactone D (4), and the corresponding 7-epimers have been synthesized starting from d-glucose. The key step in the synthesis of 1 and 2 is a new one-pot sequence comprised of a Z-selective Wittig olefination/lactonization/β-elimination. Preparation of 3 and 4 included the final 5-endo-trig spirocyclization of 1 and 2. The synthesized products were evaluated for their in vitro antiproliferative activity against selected tumor cell lines.",10.1021/ol302860z,2012-11-16,0.5993111790596916
Tetrahedron,"Synthesis of the 5R, 8R, 9S, 11R dephosphorylated derivative of CI-920, a novel antitumor agent.",,10.1016/s0040-4039(00)80201-4,1988-01-01,0.5993107155656772
Tetrahedron,Synthesis in the series of lycopodium alkaloids VIII. The total synthesis of annotinine,,10.1016/s0040-4039(01)89941-x,1967-01-01,0.5993096851507066
Organic Letters,Asymmetric Total Synthesis of Apratoxin D,"The first asymmetric total synthesis of the marine natural product apratoxin D, a highly potent inhibitor of H-460 human lung cancer cell growth (IC(50) value of 2.6 nM), is described. Asymmetric N-amino cyclic carbamate (ACC) α,α-bisalkylation was utilized to establish the isolated C-37 methyl group with excellent selectivity. Other key asymmetric transformations employed were an Evans syn-aldol and a Paterson anti-aldol, both of which also proceeded with excellent stereoselectivity.",10.1021/ol302309c,2012-10-11,0.5993087081805094
Organic Letters,Radiolabeling of Siamenoside I with Carbon-14,The synthesis of radiolabeled [25- 14 C]-siamenoside I following a synthetic route developed using unlabeled materials is disclosed. The synthesis features an early stage labeling of the mogrol’s C25 via an oxidative cleavage–reconstruction strategy and regioselective glycosylations directed by protecting group manipulations. This route provided access to adequate amounts of [25- 14 C]-siamenoside I for in vivo ADME and PK studies.,10.1021/acs.orglett.4c04537,2025-01-13,0.5993021828332362
Tetrahedron,"Synthetic studies on highly oxygenated quassinoids: Total synthesis of (±)-14β,15β-dihydroxyklaineanone",,10.1016/0040-4039(96)00340-1,1996-04-01,0.5992797812984255
Organic Letters,"Total Syntheses of (+)-Aigialospirol and (+)-7′,8′-Dihydroaigialospirol by a One-Pot Stepwise Approach","(+)-Aigialospirol and (+)-7′,8′-dihydroaigialospirol are known to be spiroketal polyketide-type natural products isolated from mangrove-derived fungus Aigialus parvus BCC 5311. These polyketides are structurally characterized by fusing resorcylic acid lactone and spiroketal moieties containing six asymmetric carbon centers. In this paper, we describe concise and stereoselective syntheses of these natural products based on biosynthesis-inspired transformation in nine steps. The total syntheses are highlighted by a one-pot stepwise synthesis involving (i) stereoselective lactone ring formation from a chiral epoxide, (ii) reduction of alkyne, (iii) global deprotection, and (iv) spiroketal formation, which are performed in the final step of the total synthesis.",10.1021/acs.orglett.5c00484,2025-03-20,0.5992735671288147
Tetrahedron,"Stereoselective nucleophilic substitution of 6-(tert-butyldimethylsilyloxy)-3,6-dihydro-2H-pyran-3-yl acetate: application to the synthesis of a NK1 receptor antagonist",,10.1016/j.tetlet.2007.03.104,2007-03-24,0.5992733537480598
Tetrahedron,Enantioselective route to ferrugine and its methyl analogue via aldol deoxygenation,,10.1016/j.tetlet.2009.10.045,2009-10-15,0.5992721932524335
Tetrahedron,Total synthesis of cyclophellitol starting from furan,,10.1016/s0040-4039(00)79144-1,1992-09-01,0.5992717616149272
Organic Letters,Sequential Acid/Base-Catalyzed Polycyclization of Tryptamine Derivatives. A Rapid Access to Büchi's Ketone,"[reaction: see text] The development of an efficient and diastereoselective methodology that allows the rapid construction of the tetracyclic core of the Aspidosperma and Strychnos alkaloid families is described. Our approach relies upon two key steps: a sequential silica gel/potassium tert-butoxide polycyclization of a tryptamine precursor and a tandem oxidative decarboxylation/ring-closing reaction. The assembly of Büchi's ketone, a key intermediate in the synthesis of vindorosine, has been accomplished using this approach.",10.1021/ol0521127,2005-10-21,0.5992666503382668
Tetrahedron,Bisubstrate-type inhibitor of sialyltransferases,,10.1016/s0040-4039(02)02272-4,2002-12-01,0.5992652247630884
Tetrahedron,"An efficient route to S-N-(9-fluorenylmethoxycarbonyl)-4′-(1-azi-2,2,2-trifluoroethyl)phenylalanine",,10.1016/s0040-4039(00)60743-8,1994-06-01,0.5992583724711097
Tetrahedron,An efficient approach for the total synthesis of balticolid,,10.1016/j.tetlet.2019.151027,2019-08-12,0.5992525553031645
Angewandte Chemie International Edition,"Modular, Scalable Total Synthesis of Lapparbin with a Noncanonical Biaryl Linkage","We report the development of a novel synthetic approach for the highly strained atrop-Tyr C-6-to-Trp N-1' linkage, which can be executed on a decagram scale using a modular strategy involving palladium-catalyzed C-H arylation followed by Larock macrocyclization. The first total synthesis of lapparbin (1) was achieved by applying this synthetic strategy. Furthermore, the modular synthesis utilizing C-H arylation and Larock macrocyclization, discovered in the total synthesis of lapparbin (1), was demonstrated to be applicable to various arbitrary biaryl linkages, including non-natural types.",10.1002/anie.202409987,2024-07-15,0.5992444487439678
Organic Letters,Synthesis of Geranyl <i>S</i>-Thiolodiphosphate. A New Alternative Substrate/Inhibitor for Prenyltransferases,The tris(tetra-n-butylammonium) salt of thiopyrophosphate 5 was prepared from trimethyl phosphate in four steps. Treatment of geranyl bromide with 5 gave an 80% yield of geranyl S-thiolodiphosphate (6). Thiolodiphosphate 6 is substantially less reactive than geranyl diphosphate (7) in the prenyl transfer reaction catalyzed by farnesyl diphosphate synthase and is a good inhibitor of the enzyme.,10.1021/ol006055n,2000-07-01,0.599242214879326
Tetrahedron,"The unambiguous synthesis of lignans of the 2,6-diaryl-3,7-dioxabicyclo-[3.3.0]octane series. The synthesis of eudesmin and 4,8-dihydroxysesamin.",,10.1016/s0040-4039(01)93697-4,1979-01-01,0.5992414617500933
Organic Process Research & Development,Practical Large-Scale Synthesis of 6-Bromo-2-naphthylmethanesulfonamide Using Semmler–Wolff Reaction,"A practical, scalable synthetic process for a sulfonamide was developed featuring a Semmler–Wolff aromatization as the key step. The optimized reaction conditions using HCl in HOAc give directly the desired naphthylamine in high yield as opposed to a naphthylacetamide commonly formed in the Semmler–Wolff reactions. One little known byproduct of anomalous rearrangement, ketoamine, was observed and a mechanism proposed to explain its formation. Employing the optimized process, 360 kg was prepared to support drug development.",10.1021/op500247h,2014-11-21,0.5992351236014606
Angewandte Chemie International Edition,Total Synthesis and Structural Elucidation of (−)‐Delactonmycin,"The key steps in the total synthesis of delactonmycin (1) involved a Wittig olefination, a Negishi coupling, and an aldol reaction. The polyketide, which was isolated from Streptomyces sp., displays potent inhibitory activity of the nucleo-cytoplasmic translocation of the HIV-1 regulatory protein Rev.",10.1002/anie.200351347,2003-07-02,0.5992286062899532
Tetrahedron,Efficient three-step sequence for the deamination of α-aminoesters. Application to the synthesis of CysLT1 antagonists,,10.1016/j.tetlet.2009.03.118,2009-03-23,0.5992260278979982
Angewandte Chemie International Edition,"Total Syntheses of (−)‐Conidiogenone B, (−)‐Conidiogenone, and (−)‐Conidiogenol","Cyclopianes are novel diterpenes featuring a highly strained 6/5/5/5 tetracyclic core embedded with 6-8 consecutive stereocenters. The concise total syntheses of (-)-conidiogenone B, (-)-conidiogenone, and (-)-conidiogenol have been accomplished in 14-17 steps. The present work features a HAT-mediated alkene-nitrile cyclization to access the cis-biquinane, a Nicholas/Pauson-Khand reaction to construct the linear triquinane, and a Danheiser annulation to afford the congested angular triquinane skeleton.",10.1002/anie.202007247,2020-06-05,0.5992191375382493
Tetrahedron,Asymmetric synthesis of (S)- and (R)-norketamine via Sharpless asymmetric dihydroxylation/Ritter amination sequence,,10.1016/j.tetlet.2015.04.050,2015-04-17,0.5992156862394779
Journal of Organic Chemistry,Total Synthesis of the Putative Structure of Didemniserinolipids A and C,"The total syntheses of the putative structure of serinolipid didemniserinolipids A and C have been achieved in 12 or 13 longest linear steps by divergent strategies starting from chiral pool methyl d-mannopyranoside, respectively. The key transformations include a sequential reaction of Bernet-Vasella-type reductive elimination and Horner-Wadsworth-Emmons in a one-pot process and a cascade reaction of desilylation/deacetalization/selective intramolecular spiroketalization involving the generation of the critical 6,8-dioxabicyclo[3.2.1]octane scaffold. Discrepancies in the spectroscopic data of the synthetic samples and natural products revealed that the original assignments of didemniserinolipids A and C were misassigned and warrant revision.",10.1021/acs.joc.5c00169,2025-05-22,0.5992137083323109
Journal of Organic Chemistry,A Catalytic Asymmetric Synthesis of Chiral Glycidic Acid Derivatives through Chiral Dioxirane-Mediated Catalytic Asymmetric Epoxidation of Cinnamic Acid Derivatives,"A novel and practical asymmetric synthesis of chiral glycidic acid derivatives involving methyl (2R,3S)-3-(4-methoxyphenyl)glycidate ((2R,3S)-2a), a key intermediate for diltiazem hydrochloride (1), was developed. Treatment of methyl (E)-4-methoxycinnamate ((E)-3a) with chiral dioxirane, generated in situ from a catalytic amount (5 mol %) of an 11-membered C(2)-symmetric binaphthyl ketone (R)-7a, provided (2R,3S)-2a in 92% yield and 80% ee. Other cinnamic acid esters and amides were epoxidized by the use of the same procedure to give the corresponding chiral glycidic acid derivatives with up to 95% yield and 92% ee. Higher enantioselectivities in the asymmetric epoxidation of (E)-cinnamates than that of (E)-stilbene derivatives were observed and were proposed to be attributed to a dipole-dipole repulsion between oxygen atoms of an ester group in the cinnamates and those of the lactone moieties in the binaphthyl dioxirane.",10.1021/jo049893u,2004-05-19,0.5992124886167584
Organic Letters,Synthesis of Analogues of Griseusin A,"The synthesis of pyranonaphthoquinone-spiroacetals ( 3 and 4 ), which are synthetic analogues of the pyranonaphthoquinone antibiotic griseusin A ( 1 ) is reported. The oxygenated substituents on the spiroacetal ring were introduced onto the key naphthalene intermediate ( 5 ) using an anti asymmetric aldol reaction. The pyranonaphthoquinone skeleton was then assembled via furofuran annulation to naphthoquinone ( 22 ) to construct a furonaphthofuran ring followed by oxidative rearrangement to the furonaphthopyran ring.",10.1021/ol991020c,1999-09-25,0.5992114848052084
Angewandte Chemie International Edition,"Total Syntheses of Norrisolide‐Type <i>Spongian</i> Diterpenes Cheloviolene C, Seconorrisolide B, and Seconorrisolide C","The first total syntheses of three unusual norrisolide-type rearranged spongian diterpenes, cheloviolene C, seconorrisolide B, and seconorrisolide C, have been accomplished via a common intermediate through late-stage ring-scissoring. The synthesis features a Wolff ring contraction for the synthesis of the trans-hydrindane system, and a crucial retro Diels-Alder reaction/intramolecular ene cyclization for the rapid stereoselective construction of the furo[2,3-b]furan system, which is commonly seen in rearranged spongian diterpenes.",10.1002/anie.202005600,2020-05-06,0.5992078536815505
Synthesis,"Synthesis of a 6<i>H</i>-Pyrazolo[4,5,1-<i>de</i>]acridin-6-one Derivative: A Useful Intermediate of Antitumour Agents","All articles of this category A 6 H -pyrazolo[4,5,1- de ]acridin-6-one derivative, a useful intermediate of antitumor agents, was prepared by a facile synthetic route from 2-bromobenzoic acid and 6-nitroindazole involving a halogenocopper(I)-catalyzed Ullmann coupling reaction and Friedel-Crafts cyclization.",10.1055/s-1994-25408,1994-01-01,0.5992060485028116
Tetrahedron,En route to hexaaza-kekulene,,10.1016/s0040-4039(00)95046-9,1985-01-01,0.5992035107969573
Synthesis,"Metabolism of Diltiazem: A Short Efficient Synthesis of N,N-Didesmethyldiltiazem - An Important Product of N-Demethylation","An important product of CYP-450 catalyzed N-demethylation of diltiazem is the primary amine didesmethyldiltiazem. An efficient two-step synthesis of this metabolite was developed via N-alkylation of (2S,3S)-cis-3-acetoxy-2,3-dihydro-2-(4-methoxy­phenyl)-1,5-benzothiazepin-4-(5H)-one with 2-(t-Boc-amino)ethyl bromide (K2CO3) followed by removal of the t-Boc protecting group using TFA. This method avoids the use of a nitrogen mustard electrophile (2-bromoethylamine) and the problematic selective O-acetylation of the HCl salt of the intermediate primary amino alcohol, thus providing the necessary metabolic standard.",10.1055/s-0030-1258410,2011-01-12,0.599200103344755
Organic Process Research & Development,"Development of a Novel Process for the Kilogram-Scale Synthesis of Spiro[1<i>H</i>-pyrido[2,3-<i>d</i>][1,3]oxazine-4,4′-piperidine]-2-one","Spiro[1 H -pyrido[2,3- d ][1,3]oxazine-4,4′-piperidine]-2-one ( 3 ) is a key building block in many biologically active compounds. The synthesis of this compound, as reported in the literature, is low-yielding. We have discovered and developed a robust, high-yielding process to generate 3 as a bis-HCl salt using alternative starting materials and reaction conditions. The developed process was successfully demonstrated on a kilogram scale. A two-batch kilo lab campaign generated the bis-HCl salt of 3 in >99 HPLC area percent purity and 77% overall yield.",10.1021/acs.oprd.8b00202,2018-07-26,0.5991722140351899
Tetrahedron,A new irreversible inhibitor of soybean lipoxygenase; relevance to mechanism,,10.1016/s0040-4039(00)84855-8,1986-01-01,0.5991721050681468
Organic Process Research & Development,"An Efficient, Practical Approach to the Synthesis of 2,4-Disubstituted Thiazoles and Oxazoles:  Application to the Synthesis of GW475151","A new method for the synthesis of 2,4-disubstituted oxazoles and thiazoles and 2,4,5-trisubstituted oxazoles from readily available starting materials is described. The methodology has been applied on multigram scale and involves transfer of oxidation state through a molecular framework. In particular the oxazole-containing amino acid fragment of the 5,5- trans -fused lactam GW475151, 1, has been prepared in excellent yield and purity.",10.1021/op000086g,2000-11-17,0.5991682167893454
Tetrahedron,"Enantioselective synthesis of axially chiral 3-bromo-4-alkoxy-2,6-dimethyl-5-(naphthalen-1-yl)pyridines via an asymmetric Suzuki–Miyaura cross-coupling reaction",,10.1016/j.tetlet.2016.09.024,2016-09-12,0.5991676793639588
Journal of Organic Chemistry,Domino Reaction of α-Acetyl-α-carbamoyl Ketene Dithioacetals with Vilsmeier Reagents:  A Novel and Efficient Synthesis of 4-Halogenated 2(1<i>H</i>)-Pyridinones,A novel and efficient route to 4-halogenated N-substituted 2(1H)-pyridinones has been developed via a one-pot domino process of readily available alpha-acetyl-alpha-carbamoyl ketene dithioacetals with Vilsmeier reagents. These 4-halogenated-2(1H)-pyridinones constitute useful intermediates due to the easy elaboration on either the pyridinone core (by the displacement of the halogen atom) or functionality transformation (dithiocarbonyl functionality) and have proven to be a useful synthetic scaffold in the synthesis of the bio- and pharmacologically important fused-ring diazepine core.,10.1021/jo701742q,2007-11-01,0.5991657970276396
Tetrahedron,Enantioselective synthesis of highly functionalised cyclohexanones starting from R-(−)-carvone,,10.1016/s0040-4039(98)01367-7,1998-09-01,0.5991561491997593
Journal of the American Chemical Society,Highly Flexible Synthesis of Chiral Azacycles via Iridium-Catalyzed Hydrogenation,"A range of saturated chiral azacycles has been prepared in high yield and with high selectivity from simple starting materials. A modular approach with ring-closing metathesis as a key step was used to produce a number of five-, six-, and seven-membered cyclic alkenes. Asymmetric hydrogenation catalyzed by N,P-ligated iridium complexes gave saturated azacycles in high optical purity. This methodology was demonstrated in the synthesis of a pharmaceutical precursor.",10.1021/ja103901e,2010-06-17,0.59915127017431
Synthesis,"A New Synthesis of 4-Arylcoumarins and Isocoumestans (6-Oxo-6<i>H</i>-benzo[2,3-<i>c</i>] [1]benzopyrans)",,10.1055/s-1977-24494,1977-01-01,0.5991469768146703
Synthesis,"Application of the Anionic Oxy-Cope Rearrangement to Stereocontrolled Synthesis of the A/B Subunit of Cytoxic 8,9-Seco-<i>ent</i>-kaurenes","All articles of this category Methodology is described for expedient synthesis of the A/B framework of 8,9-seco- ent -kaurenes and for introduction of the 5-methylene-2-cyclopentenone moiety. In the first part of the study, a sequence of only six steps is necessary to convert 2-(hydroxymethylene) cyclohexanone to a key functionalized intermediate. Five of the transformations are 100% stereocontrolled as a direct result of complementary steric biases that operate in the desired direction. The final target is arrived at by selective protection/oxidation of the oxygenated centers. This first synthetic entry to the structural core of the titled diterpenes is expected to guide the future de novo acquisition of these cytotoxic agents.",10.1055/s-1992-34185,1992-01-01,0.5991466772859588
Synthesis,"A Ruthenium-Catalyzed C–H Activation Strategy as an Efficient Shortcut in the Total Synthesis of 6,8-Dimethoxy-1,3-dimethylisoquinoline","A short and convenient total synthesis of 6,8-dimethoxy-1,3-dimethylisoquinoline, employing a C–H activation/alkenylation strategy, is reported. The approach involves the CeCl3·7H2O-promoted methoximation of 2,4-dimethoxyacetophenone and a methoxime-directed ruthenium-catalyzed allylation. This was followed by a one-pot, ruthenium-catalyzed allyl to propenyl isomerization and a microwave-assisted 6π-azaelectrocylization to complete the sequence. This approach, which entails a shortcut in the synthetic management of the three-carbon side chain, is an improved and more efficient route toward the natural product, which facilitated its access in just three steps and 27.3% overall yield.",10.1055/s-0037-1610720,2019-07-16,0.5991395959991926
Synthesis,"Synthesis of Tribenzotropone by Ring Expansion of Phenanthrene-9,10-dione","Tribenzotropone was efficiently synthesized by a ring-expansion method from readily available phenanthrene-9,10-dione via a ring-opened diketone as a key intermediate; the diketone was prepared by nucleophilic addition of allyl and vinyl groups, followed by an oxidative ring-opening reaction with lead(IV) acetate. Ring closure by an intramolecular Diels–Alder reaction and subsequent dehydrogenation produced tribenzotropone in 38% overall yield. Ring closure by a Morita–Baylis–Hillman reaction, on the other hand, produced a dibenzo-fused nonanedione in 22% overall yield.",10.1055/s-0034-1381045,2015-08-07,0.5991390722644827
Organic Letters,Asymmetric Total Synthesis of Asperversin A,Asperversin A represents the first example of a steroid–sterigmatocystin heterodimer. We report the concise asymmetric total synthesis of this natural product in 11 steps (the longest linear sequence). The polycyclic ring system was constructed by a cascade dialdehyde cyclization and the late stage xanthene formation by a phenol-assisted reductive alkylation and a S N Ar reaction. The acetal linkage with ergosterol peroxide was furnished by a glycosylation-inspired approach.,10.1021/acs.orglett.1c00366,2021-03-03,0.5991383581522443
Tetrahedron,"Practical synthesis of 9-(2,3-dideoxy-2-fluoro-β- d - threo -pentofuranosyl)adenine (FddA) via a purine 3′-deoxynucleoside",,10.1016/s0040-4039(01)00136-8,2001-03-01,0.5991376085163078
Journal of Organic Chemistry,"[4 + 2] Cycloadditions of 1-Phosphono-1,3-butadienes with Nitroso Heterodienophiles: A Versatile Synthetic Route for Polyfunctionalized Aminophosphonic Derivatives","The hetero-Diels-Alder (HDA) reaction of 1-(diethoxyphosphonyl)-1,3-butadiene, 1-(dibenzyloxyphosphonyl)-1,3-butadiene, and 1-(diethoxyphosphonyl)-3-tert-butyldimethylsilyloxy-1,3-butadiene with various nitroso heterodienophiles has been investigated as a new synthetic route for aminophosphonic derivatives. The HDA cycloadditions regioselectively led to the proximal isomers, i.e., presenting the NR(3) group in the meta position regarding the phosphonate substituent. From the resulting 6-phosphono-3,6-dihydro-1,2-oxazine cycloadducts, a limited number of chemical steps were allowed to obtain a significant variety of aminophosphonic compounds of potential interest in medicinal chemistry. This has been illustrated through the synthesis of (Z)-4-(o-tolylamino)-1-hydroxybut-2-enylphosphonic acid, diethyl 3,4-dihydroxy-1-o-tolylpyrrolidin-2-yl-2-phosphonate, 4-(o-tolylamino)-1,2,3-trihydroxybutylphosphonic acid, diethyl 3-(2-(o-tolylamino)-1-hydroxyethyl)oxiran-2-yl-2-phosphonate, and diethyl 4,5-dihydroxymorpholin-6-yl-6-phosphonate.",10.1021/jo100230r,2010-07-21,0.5991319881348306
Journal of the American Chemical Society,Total Synthesis of Vilmoraconitine,"-diterpenoid alkaloids, which architecturally features an unprecedented heptacyclic core possessing a rigid cyclopropane unit. Here, we report the first total synthesis of vilmoraconitine relying on strategic use of efficient ring-forming reactions. Key steps include an oxidative dearomatization-induced Diels-Alder cycloaddition, a hydrodealkenylative fragmentation/Mannich sequence, and an intramolecular Diels-Alder cycloaddition.",10.1021/jacs.3c00318,2023-02-13,0.5991285097131975
Journal of Organic Chemistry,"Gram-Scale Synthesis of 2,5-Difluoro-7,7,8,8-tetracyanoquinodimethane (F<sub>2</sub>-TCNQ)","The molecule 2,5-difluoro-7,7,8,8-tetracyanoquinodimethane (F 2 -TCNQ) is an organic semiconductor with many promising properties, including high charge mobility (μ). However, an efficient gram-scale synthesis of F 2 -TCNQ has not been fully documented. Herein, we report a synthesis of F 2 -TCNQ via a three-step sequence that affords F 2 -TCNQ in 58% cumulative yield. This synthesis was used to prepare more than 1 g of F 2 -TCNQ.",10.1021/acs.joc.0c00053,2020-03-02,0.5991082423442567
Journal of Organic Chemistry,Synthesis of the ABC Ring System of Manzamine A,"A synthesis of the core ABC ring system of the manzamine alkaloids is described, starting from arecoline. The key steps involve a Claisen rearrangement to set up a 4-substituted-3-methylenepiperidine and a stereoselective azomethine ylide dipolar cycloaddition reaction. Condensation of the aldehyde 6 and sarcosine ethyl ester hydrochloride salt gives an intermediate azomethine ylide, which undergoes an intramolecular cycloaddition reaction to set up two new rings and three new chiral centers stereoselectively. The aldehyde 6 was not a suitable substrate for related azomethine ylide cycloaddition reactions with other amines. However, the related dimethyl acetal 26 could be condensed with a variety of amines to give the desired tricyclic products. The cycloaddition reaction with N-methyl or N-allyl glycine ethyl ester gave almost exclusively the exo adduct, whereas cycloaddition with glycine ethyl ester gave the endo adduct.",10.1021/jo016376s,2002-07-27,0.5990935440398055
Organic Letters,"Regiospecific, Enantiospecific Total Synthesis of the Alkoxy-Substituted Indole Bases, 16-<i>e</i><i>pi</i>-<i>N</i><sub>a</sub>-Methylgardneral, 11-Methoxyaffinisine, and 11-Methoxymacroline as Well as the Indole Alkaloids Alstophylline and Macralstonine","A regiospecific, enantiospecific approach to the synthesis of ring-A-substituted indole alkaloids was developed via a doubly convergent strategy. The asymmetric Pictet-Spengler reaction and enolate-driven palladium cross-coupling processes were both executed in stereospecific fashion and served as the stereochemical basis of this approach. The synthesis of 16-epi-N(a)-methylgardneral (15), 11-methoxyaffinisine (16), and 11-methoxymacroline (22) has been accomplished in high yield and in enantiospecific fashion. Moreover, the key C-19 ketosarpagine system (borane adducts) 19a,b employed for the construction of 11-methoxymacroline (22) was also transformed into alstophylline 25, which resulted in completion of the total synthesis of the bisindole macralstonine (1). [reaction: see text]",10.1021/ol020101x,2002-09-11,0.5990934780365145
Organic Process Research & Development,Development of an Efficient Process for the Preparation of Sch 39166:  Aziridinium Chemistry on Scale,A large-scale synthesis of a tricyclic D1/D5 dopamine antagonist based on regio- and stereoselective ring opening of an aziridinium ion with a Grignard reagent was optimized and scaled up.,10.1021/op0402026,2004-08-03,0.5990924501224382
Organic Letters,A Convergent Approach toward the C1−C11 Subunit of Phoslactomycins and Formal Synthesis of Phoslactomycin B,"The preparation of the C1-C11 subunit of phoslactomycins, and a formal synthesis of phoslactomycin B, were achieved by a convergent strategy involving the chelation-controlled addition of an alkynyl Grignard reagent to an alpha-alkoxy ketone. Catalytic enantioselective reductions of acetylenic ketones and a [2,3]-Wittig rearrangement were utilized as key steps to control the configuration of the C4, C5, and C9 stereocenters.",10.1021/ol8029142,2009-01-26,0.5990888833366802
Organic Letters,"Total Synthesis of (±)-Crinine via the Regioselective Stille Coupling and Diels−Alder Reaction of 3,5-Dibromo-2-pyrone","The regioselective synthesis and Diels-Alder cycloaddition of 3-(3,4-methylenedioxyphenyl)-5-bromo-2-pyrone provided a new synthetic route to crinine. The vinyl bromide group can be used as a handle for further derivatization.",10.1021/ol702907u,2008-01-15,0.5990800017696539
Synlett,Total Synthesis of (<i>S</i>)-Anabasine and (<i>S</i>)-Anatabine,"All articles of this category A chiral synthesis of ( S )-anabasine and ( S )-anatabine from 3-pyridinecarboxaldehyde, via a ring closing metathesis reaction (RCM) as the key step, is reported in 8 steps for both products with overall yields of 35% and 30%, respectively. piperidine alkaloid - asymmetric synthesis - allylboration - ring closing metathesis - ruthenium",10.1055/s-2000-7907,2000-01-01,0.5990791941125885
Tetrahedron,"A novel route to 2,3-disubstituted indoles via palladium-catalyzed three-component coupling of aryl iodide, o-alkenylphenyl isocyanide and amine",,10.1016/s0040-4039(02)01316-3,2002-08-01,0.5990735163415055
Tetrahedron,"Reaction of ortho-lithiated N-methylbenzamide with 1,2-Diketones: A novel highly efficient route to N-methylisoquinolin-1-one",,10.1016/0040-4039(94)02293-k,1995-01-01,0.5990708694613451
Organic Letters,Enantioselective Total Synthesis of (−)-Dehydrobatzelladine C,"The oxidation of two tethered Biginelli adducts was examined as a potential key step in total syntheses of highly oxidized batzelladine and crambescidin alkaloids. Although angular hydroxyl substitution could not be introduced, dehydrogenation was readily accomplished. This latter conversion is a key step in the first total synthesis of dehydrobatzelladine C. [structure: see text]",10.1021/ol0498141,2004-03-12,0.5990686940107041
Organic Letters,Total Synthesis of Conjugation-Ready Tetrasaccharide Repeating Units of a Multidrug-Resistant Pathogen <i>Acinetobacter baumannii</i> Strain 34 and O5,"Herein, we report the first total synthesis of conjugation-ready tetrasaccharide repeating units of Acinetobacter baumannii strain 34 and O5 comprising a common disaccharide motif [α- l -FucpNAc-(1→4)-α- d -GalpNAcA]. The installation of 1,2- cis linkages employing a disarmed 2-azido- d -galacturonic acid derivative as the donor is addressed here. The synthesis of the tetrasaccharide repeating units of A. baumannii strain 34 and O5 is accomplished via the longest linear sequences of 19 steps in 9.8% and 21 steps in 8.4% overall yields, respectively.",10.1021/acs.orglett.3c03417,2023-11-13,0.5990617912965007
Tetrahedron,An efficient and concise total synthesis of the antimalarial alkaloid quindoline,,10.1016/j.tetlet.2013.04.010,2013-04-16,0.5990590951282788
Journal of Organic Chemistry,"Biosynthesis of Terpenes. Preparation of (<i>E</i>)-1-Hydroxy-2-methyl-but-2-enyl 4-Diphosphate, an Intermediate of the Deoxyxylulose Phosphate Pathway","(E)-1-hydroxy-2-methyl-but-2-enyl 4-diphosphate (E-6) was synthesized in six reaction steps from hydroxyacetone (9) and (ethoxycarbonylmethenyl)-triphenylphosphorane (11) with an overall yield of 38%. The compound was shown to be identical with the product of IspG protein, which serves as an intermediate in the nonmevalonate terpene biosynthetic pathway.",10.1021/jo025705t,2002-05-22,0.5990590032182785
Synlett,Total Synthesis and Cytotoxic Activity of 7-O-Methylnigrosporolide and Pestalotioprolide D,"Abstract A convergent total synthesis of 7-O-methylnigrosporolide and pestalotioprolide D has been accomplished in 17 linear steps and overall yields of 1.7% and 2.6%, respectively, starting from (S)-propylene oxide and (S)-benzyl glycidyl ether. Our synthesis exploited an acetylide addition and a Shiina macrolactonization to assemble the macrocycle, a Lindlar reduction, and Wittig and Still–Gennari olefinations to construct the three alkene groups, as well as a Jacobsen hydrolytic kinetic resolution to install the stereogenic center. The selection of the silyl protecting group of the C-4 alcohol was crucial for the final deprotection step. Our synthesis also led to a hypothesis that pestalotioprolide D might be an artifact of 7-O-methylnigrosporolide. The cytotoxic activities of the two synthetic compounds against six human cancer cell lines were evaluated. Synthetic pestalotioprolide D showed more potent cytotoxic activity than 7-O-methylnigrosporolide against all the cancer cell lines tested, and the SiHa cervical cancer cell line was the most sensitive to both synthetic compounds.",10.1055/a-1792-8402,2022-03-09,0.5990563971817412
Journal of the American Chemical Society,Total Synthesis of Ryanodol,"Ryanodol (1) exists in nature in the form of the 1H-pyrrole-2-carboxylate ester derivative known as ryanodine, which is a potent modulator of the calcium release channel. The pentacyclic ABCDE-ring system of 1 is fabricated with eight oxy groups, three methyl groups, and one isopropyl group. All the eight tetrasubstituted stereocenters are concentrated within the 10-carbon ABDE framework. The total synthesis of this exceptionally complex molecule was achieved in 22 steps from the simple C2-symmetric tricycle 8. The synthetic route is based on installation of the seven stereogenic centers and formation of the four C-C bonds within the highly congested multicyclic format. The novel and flexible strategy developed here will enable the generation of chemical derivatives with different functional properties toward calcium release channels.",10.1021/ja502770n,2014-04-07,0.5990508280590517
Synthesis,A Convenient Two-Step Synthesis of 2-Arylbenzofurans,"A novel and convenient two-step synthesis of 2-arylbenzofurans is described which proceeds via a selective cross-pinacol-type coupling between a salicylaldehyde and an aromatic aldehyde, followed by an acid-promoted cyclization. One advantage of this method is that separation of the three possible pinacol products that can form during the cross-coupling is not necessary. This method is also applied to the synthesis of the 2-arylbenzofuran-containing natural product, homoegonol.",10.1055/s-0029-1217129,2009-11-20,0.5990411376062106
Angewandte Chemie International Edition,Total Synthesis and Structural Revision of a Harziane Diterpenoid,"The first total synthesis of nominal harziane diterpenoid 1 is disclosed, whose spectral characteristics did not match those of the reported natural product. Stereochemical analysis and subsequent synthesis of the epimeric tertiary alcohol led to reassignment of configuration of the natural product as shown for 2. At the heart of the synthesis is an enyne cycloisomerization that sets a key quaternary stereocenter within a cyclobutane with high diastereocontrol. The route features strategies for the synthesis of the highly congested 6-5-7-4 carbon skeleton characteristic of the caged harziane diterpenoids.",10.1002/anie.201912982,2019-11-06,0.5990372723634566
Tetrahedron,"Synthesis of pyrido[2,3,4-kl]acridines a building block for the synthesis of pyridoacridine alkaloids",,10.1016/s0040-4039(00)61150-4,1992-09-01,0.5990345937713095
Journal of Organic Chemistry,"Synthesis and Reactivity of 4-(2-Chloro-5-nitrophenyl)-1,2,3-thiadiazole. A Novel One-pot Synthesis of N-Substituted Indole-2-thiols","4-(2-Chloro-5-nitrophenyl)-1,2,3-thiadiazole undergoes ring opening to produce a thioketene intermediate that reacts with an O- or N-nucleophile, forming an ester or an amide of the aryl-substituted thioacetic acid. Intermolecular cyclization of the thioacetic acid derivative via nucleophilic substitution of halogen in the aromatic ring gives an N-substituted indole-2-thiol (in case of an N-nucleophile) or a 2-alkoxy-substituted benzo[b]thiophene (in case of an O-nucleophile). The reaction is also applicable to the synthesis of heterocyclic analogues of N-substituted indole-2-thiols: 1-butyl-1,3-dihydropyrrolo[2,3-b]pyridine-2-thione was synthesized as an example. In the presence of potassium thioacetate (an S-nucleophile) 4-nitro-2-(1,2,3-thiadiazol-4-yl)benzenethiol is formed more quickly than thiadiazole ring opening occurs, making the heterocyclic ring tolerant toward the base.",10.1021/jo0707784,2007-06-07,0.5990317036911661
Organic Process Research & Development,Short and Efficient Synthesis of the Antituberculosis Agent Pretomanid from (<i>R</i>)-Glycidol,"High Resolution Image Download MS PowerPoint Slide An efficient gram-scale synthesis of the antituberculosis agent pretomanid using straightforward chemistry, mild reaction conditions, and readily available starting materials is reported. Four different protecting groups on the glycidol moiety were investigated for their technical feasibility and ability to suppress side reactions. Starting from readily available protected ( R )-glycidols and 2-bromo-4-nitro-1 H -imidazole, pretomanid could be prepared in a linear three-step synthesis in up to 40% isolated yield. In contrast to most syntheses reported so far, deprotection and cyclization were performed in a one-pot fashion without any hazardous steps or starting materials.",10.1021/acs.oprd.3c00187,2023-09-05,0.599005454884656
Journal of the American Chemical Society,"Asymmetric Total Synthesis of <i>Cephalotaxus</i> Diterpenoids: Cephinoid P, Cephafortoid A, 14-<i>epi</i>-Cephafortoid A and Fortalpinoids M-N, P","The asymmetric total syntheses of cephalotaxus C19 diterpenoids, bearing a unique cycloheptene A ring with a chiral methyl group at C-12, were disclosed based on a universal strategy. Six members, including cephinoid P, cephafortoid A, 14- epi -cephafortoid A and fortalpinoids M-N, P, were accomplished for the first time. The concise approach relies on two crucial steps: (1) a Nicholas/Hosomi-Sakurai cascade reaction was developed to efficiently generate the cycloheptene ring bearing a chiral methyl group; (2) an intramolecular Pauson-Khand reaction was followed to facilitate the construction of the complete skeleton of target molecules. Our studies provide a new strategy for the synthetic analysis of cephalotaxus diterpenoids and structurally related polycyclic natural products.",10.1021/jacs.3c05455,2023-07-26,0.599001571598914
European Journal of Organic Chemistry,Stereoselective Synthesis of Polyhydroxycycloheptanes and Their Phosphate Derivatives from 8‐Oxabicyclo[3.2.1]octenes,Abstract The first directed synthesis of seven‐membered mono‐ and tris‐phosphates is described. The key steps involve a DIBAL‐H/DIBAL‐Cl‐mediated ring opening of 8‐oxabicyclo[3.2.1]octenes in the presence of [Ni(acac) 2 ] and stereoselective syn ‐dihydroxylation with NMO and OsO 4 . An enantioselective approach to ring opening has been examined with chiral phosphane. The phosphorylation of mono‐ and triols followed by deprotection gave the corresponding phosphates in high yields with structures similar to those of known inhibitors of myo ‐inositol monophosphatase (IMPase) and myo ‐inositol tris‐phosphate receptor ligands. The inhibitory activities of the monophosphates thus formed were evaluated against IMPase.,10.1002/ejoc.201201426,2013-03-04,0.5989986010092582
Organic Process Research & Development,Synthesis of a Spiroindolinone Pyrrolidinecarboxamide MDM2 Antagonist,"A practical synthesis of a spiroindolinone pyrrolidinecarboxamide MDM2 antagonist 2 is reported. Cycloaddition of dipolarophile 3 with imine 30 afforded a complex mixture of diastereomers that were isomerized to the desired stereoisomer 31 by heating the mixture in the presence of DBU. After hydrolysis, the resulting product was resolved with a chiral amine to give an enantiopure acid which was converted to the target product 2 . The process has been scaled up to a multihundred-gram scale. In addition, an asymmetric synthesis of 31 catalyzed by AgOAc and a chiral phosphine ligand was developed to give enantiomerically enriched 31, which was also converted to enantiopure 2 .",10.1021/op3003213,2013-01-15,0.5989980133464131
Tetrahedron,"A new xylylehe-like intermediate: 2-allylidene-5-methylene-2,5-dihydrofuran. Synthesis of [6.2], [4.4], and [4.2]furanophanes.",,10.1016/s0040-4039(01)94782-3,1978-01-01,0.5989941101235179
Synthesis,Synthesis of New (3-Aminopyrrolidin-3-yl)phosphonic Acid - A Cucurbitine Analogue - and (3-Aminotetrahydrothiophen-3-yl)phosphonic Acid via Phosphite Addition to Heterocyclic Hydrazones,"Hydrazones were prepared by condensation of carbo­cyclic and heterocyclic ketones with benzoyl- and tosylhydrazines. These hydrazones underwent nucleophilic addition with phosphite to provide efficiently (3-hydrazinopyrrolidin-3-yl)-, (3-hydrazino­tetrahydrothiophen-3-yl)-, (3-hydrazinotetrahydrofuran-3-yl)-, and (1-hydrazinocyclopentyl)phosphonates. Cleavage of the hydrazine N-N bonds followed by acidic hydrolysis of the phosphonate functions of the (3-aminoheterocyclopentyl)phosphonates gave the new (3-aminopyrrolidin-3-yl)- and (3-aminotetrahydrothiophen-3-yl)phosphonic acids. This synthesis was achieved in a four-step sequence from the appropriate ketones.",10.1055/s-2008-1067130,2008-06-11,0.5989938762585502
Synlett,Synthetic Approaches to the Bottom Half Fragment for Bryostatin 11,An approach towards the stereoselective synthesis of the bottom half fragment of bryostatin 11 is described. Key steps ­include asymmetric aldol and Saksena-Evans reduction reactions ­to construct multiple stereogenic centers and thioketalization-­lactonization reactions to form the thioketal-protected C-ring.,10.1055/s-0030-1260784,2011-06-10,0.5989927713217791
Synthesis,A New Efficient Synthesis of Spirocyclic Benzopyrans,"Starting from a protected β-amino ketone and several 3-chromanones, spirocyclic benzopyran derivatives were obtained via a Mannich type condensation",10.1055/s-2003-44353,2003-11-25,0.5989910256380313
Tetrahedron,Synthesis of (Z)- and (E)-N9-(4-hydroxy-1-buten-1-yl)adenine - new unsaturated analogues of adenosine,,10.1016/s0040-4039(00)94329-6,1990-01-01,0.5989900282732165
Journal of Organic Chemistry,Formal Total Syntheses of (+)-Prelaureatin and (+)-Laurallene by Diastereoselective Brook Rearrangement-Mediated [3 + 4] Annulation,"The formal syntheses of (+)-prelaureatin (1) and (+)-laurallene (2), halogenated eight-membered-ring ethers, are described. The key step of our strategy relies on diastereoselective construction of a trans-alpha,alpha'-disubstituted oxocene structure through a Brook rearrangement-mediated [3 + 4] annulation with acryloylsilane 9 and 6-oxa-2-cycloheptenone derivative 22'.",10.1021/jo100708n,2010-05-12,0.5989884886296652
Synlett,A Mannich-Cyclization Approach for the Asymmetric Synthesis of Saturated <i>N</i>-Heterocycles,"A concise asymmetric synthesis of disubstituted N-heterocycles is reported. Our approach utilizes an optimized Mannich reaction of functionalized aldehydes, followed by a novel dehydrative cyclization mediated by the Staab reagent (1,1′-carbonyldiimidazole, CDI). The method was applied to the synthesis of azetidines, piperidines and pyrrolidines.",10.1055/s-2004-835622,2004-10-22,0.5989862347817969
Journal of Organic Chemistry,"Preparation of Amino-Substituted Indenes and 1,4-Dihydronaphthalenes Using a One-Pot Multireaction Approach: Total Synthesis of Oxybenzo[<i>c</i>]phenanthridine Alkaloids","Allylic trichloroacetimidates bearing a 2-vinyl or 2-allylaryl group have been designed as substrates for a one-pot, two-step multi-bond-forming process leading to the general preparation of aminoindenes and amino-substituted 1,4-dihydronaphthalenes. The synthetic utility of the privileged structures formed from this one-pot process was demonstrated with the total synthesis of four oxybenzo[c]phenanthridine alkaloids, oxychelerythrine, oxysanguinarine, oxynitidine, and oxyavicine. An intramolecular biaryl Heck coupling reaction, catalyzed using the Hermann-Beller palladacycle was used to effect the key step during the synthesis of the natural products.",10.1021/jo5014492,2014-07-24,0.5989723525094648
Journal of Organic Chemistry,Total Synthesis of (−)-Hymenosetin,"The 3-decalinoyltetramic acid (-)-hymenosetin and its N-methyl analogue were prepared in 11 and 8 steps, respectively, from (+)-citronellal using an intramolecular Diels-Alder reaction as the key step. This method represents the first example for the synthesis of a 3-decalinoyltetramic acid with a free NH moiety. The stereochemistry of the title compound, an unnatural diastereomer, and of a decalin building block was studied in detail using circular dichroism spectroscopy in the IR and UV/VIS freqeuncy range. This allowed to determine the absolute configuration of the natural product and to plan the synthetic route.",10.1021/acs.joc.5b02526,2015-12-04,0.5989712529849376
European Journal of Organic Chemistry,"Synthesis of Tetrahydroquinoline‐Embedded Bridged Benzothiaoxazepine‐1,1‐dioxides","A diastereoselective synthesis of previously unknown tetrahydroquinoline‐containing bridged benzothiaoxazepine‐1,1‐dioxides is presented. The three‐step protocol uses readily available N ‐aryl‐2‐fluorobenzenesulfonamides and trans ‐2,3‐epoxy‐cinnamyl‐alcohol‐derived tosylates as the starting materials, involves N ‐alkylation of sulfonamides, intramolecular epoxide ring‐opening, and S N Ar reactions as the reaction steps, and requires only one chromatographic purification to access the desired products in good overall yields.",10.1002/ejoc.201701152,2017-10-17,0.5989650024520358
Synlett,An Enantiospecific Approach to Tetraquinane Diterpenes Crinipellins: Synthesis of Norcrinipellins,An enantiospecific approach to the synthesis of tetraquinane diterpene crinipellins is described. The cyclopentane ring in campholenaldehyde was identified as the B ring. Two rhodium carbenoid CH insertion reactions for the construction of A and C rings and an intramolecular Michael addition reaction for the D ring of crinipellins were employed as key strategies for the enantiospecific synthesis of norcrinipellins.,10.1055/s-0031-1289533,2011-10-19,0.5989584535374686
Organic Process Research & Development,Synthesis of Nirmatrelvir: Development of Magnesium Sulfate-Mediated Aminolysis for the Manufacture of the Eastern Fragment,"Nirmatrelvir is a potent, selective, and orally bioavailable inhibitor of SARS-CoV-2 M pro . In this paper, we report the development of a magnesium sulfate (MgSO 4 )-mediated aminolysis for the synthesis of ( S )-2-amino-3-[( S )-2-oxopyrrolidin-3-yl]propenamide hydrogen chloride, the eastern fragment of nirmatrelvir. Previous synthesis of this building block required a protecting group, high equivalents of ammonia, and a long reaction time and generated materials with moderate potency and high levels of residual solvents. We determined that MgSO 4, a widely available and low-cost material, accelerates the desired aminolysis reaction and suppresses the formation of impurities without the need for high equivalents of ammonia or a protecting group. Our understanding of the solubility profile of this intermediate facilitated the development of a robust isolation protocol to purge byproducts and generate high-potency materials regardless of the source of the precursors. The MgSO 4 -mediated aminolysis process was demonstrated to produce >350 kg of the building block per batch.",10.1021/acs.oprd.3c00252,2023-11-22,0.5989555281276028
Synthesis,A Convenient Large Scale Synthesis of Protected D-Ribonolactone From D-Ribose,"All articles of this category A simple and efficient synthesis of protected D-ribonolactone, a key chiral precursor used in the syntheses of neplanocin A and cyclopentenyleytosine from readily available D-ribose is reported.",10.1055/s-1990-27085,1990-01-01,0.5989543374186077
Organic Letters,Diastereoselective Synthesis of α-Tocopherol: A New Concept for the Formation of Chromanols,"A diastereoselective synthesis of alpha-tocopherol 1 (93% de) was achieved via two key steps, (i) a highly diastereoselective Shi epoxidation of a trisubstituted alkene and (ii) an acid supported, ""anti-Baldwin"" epoxide ring opening under inversion of configuration leading to the 6-membered chromanol ring.",10.1021/ol8019583,2008-10-21,0.5989506289960722
Organic Letters,Total Synthesis and Biological Evaluation of Verticipyrone and Analogues,"[reaction: see text] Total synthesis of verticipyrone, a novel NADH-fumarate reductase inhibitor, has been accomplished by a convergent approach using novel ""Reverse Julia olefination"" method. During total synthetic studies, we also prepared and evaluated several synthetic verticipyrone analogues, some of which exhibited more potent antiparasitic activity than the natural verticipyrone.",10.1021/ol0626140,2006-12-05,0.5989494388369193
Organic Letters,Total Synthesis of Trisaccharide Repeating Unit of <i>O</i>-Specific Polysaccharide of <i>Pseudomonas fluorescens</i> BIM B-582,"The first total synthesis of the trisaccharide repeating unit of the O-specific polysaccharide of Pseudomonas fluorescens BIM B-582 is reported. This efficient synthesis involves consecutive 1,2- cis glycosylations including β-l-rhamnosylation and α selective coupling of rare 4-deoxy-d- xylo-hexose as the key steps. The synthetic trisaccharide is equipped with an aminopropyl linker at the reducing end to allow for conjugation to proteins and microarrays for further immunological studies.",10.1021/acs.orglett.8b02669,2018-09-06,0.5989428077113392
Organic Letters,Construction of Indole Structure on Pyrroloindolines via AgNTf<sub>2</sub>-Mediated Amination/Cyclization Cascade: Application to Total Synthesis of (+)-Pestalazine B,"An N -linked indole structure was constructed on the 3a-position of pyrroloindoline derivatives via a cascade process involving silver-mediated amination of bromopyrroloindolines with 2-ethynylanilines with subsequent 5- endo-dig cyclization. In this reaction, AgNTf 2 was used as a tandem reagent, which activated the bromo group as a σ-Lewis acid and the alkyne moiety as a π-Lewis acid. Switching from the initial step to the second step was conducted by controlling the temperature. This protocol was applied to the synthesis of various pyrroloindolines, α-carboline, and furoindolines and the total synthesis of a dimeric indole alkaloid, (+)-pestalazine B.",10.1021/acs.orglett.9b01399,2019-05-22,0.5989374435254317
Synthesis,Palladium-Catalyzed Copper-Free Sonogashira Coupling of 2-Bromoarylcarbonyls: Synthesis of Isobenzofurans via One-Pot Reductive Cyclization,"Palladium-catalyzed copper-free Sonogashira coupling of 2-bromocarbonyls is presented. This method afforded the 2-alkynylaryl carbonyls, useful synthons for the accomplishment of many carbocyclic and heterocyclic motifs. Significantly, the strategy was extended to the one-pot synthesis of isobenzofurans via reduction followed by intramolecular 5-exo-dig cyclization.",10.1055/s-0036-1588513,2017-08-02,0.5989350419794789
Journal of the American Chemical Society,Total Synthesis of Gambierol,The convergent total synthesis of gambierol (1) is described. The octacyclic ether framework of 1 was constructed via the intramolecular allylation of alpha-chloroacetoxy ether followed by ring-closing metathesis. A modified Stille coupling was successfully applied to the synthesis of the triene side chain.,10.1021/ja028726d,2002-12-11,0.5989306474777297
Angewandte Chemie International Edition,Convergent Total Synthesis of (+)‐Ophiobolin A,"At long last: The enantioselective total synthesis of the title compound, which was isolated in 1958, proceeds by a convergent approach. The assembly of the C, D-ring fragment and the A-ring fragment of the core structure is achieved by employing a Reformatsky-type reaction. The eight-membered carbocyclic B ring is efficiently constructed by a challenging ring-closing metathesis (see scheme).",10.1002/anie.201104447,2011-09-13,0.598926887580929
Synthesis,Stereoselective Synthesis of Aporphine Alkaloids Using a Hypervalent Iodine(III) Reagent-Promoted Oxidative Nonphenolic Biaryl Coupling Reaction. Total Synthesis of (<i>S</i>)-(+)-Glaucine,"The aporphine alkaloid (+)-glaucine (8a) and two other analogues 8b,c have been synthesized in good yield and high ee from the appropriate 1,2-diarylethylamine derivatives, which were in turn prepared using (S)-(+)-phenylglycinol as chiral support. Next, a sequence of simple transformations: N-alkylation with bromoacetaldehyde diethyl acetal, N-methylation, Pommeranz-Fritsch cyclization, and ionic hydrogenation led to the key intermediate, optically active, 1-benzyltetrahydroisoquinolines 7a-c. The final C-ring closure step was performed by C-C biaryl bond formation by an hypervalent iodine(III) reagent promoted oxidative coupling, affording the target heterocycles 8a-c in good yields and with no racemization at the formerly created stereogenic center.",10.1055/s-2004-816009,2004-01-01,0.5989261811769601
European Journal of Organic Chemistry,A Highly Enantioselective Alkene Methoxycarbonylation Enables a Concise Synthesis of (<i>S</i>)‐Flurbiprofen,"A highly enantioselective synthesis of ( S )‐flurbiprofen methyl ester in two steps from commercially available 4‐bromo‐2‐fluoro‐1,1′‐biphenyl is shown. [PdCl 2 (( S )‐xylyl‐phanephos)] catalyst is used to accomplish both Grignard cross‐coupling and the highly enantioselective intermolecular methoxycarbonylation reaction.",10.1002/ejoc.201700791,2017-07-25,0.5989259507883335
Tetrahedron,"Enantioselective total synthesis of Glyoxalase I inhibitor using asymmetric Diels-Alder reaction of a new chiral dienophile, ()S-3-(3-triflouromethylpyrid-2-ylsulfinyl)acrylate.",,10.1016/s0040-4039(00)85252-1,1986-01-01,0.5989257618735019
Angewandte Chemie International Edition,"Total Synthesis of Dolabriferol C by a Highly Stereoselective One‐Pot Coupling of a <i>meso‐</i>3,7‐Diketone with Two Chiral Aldehydes","Total synthesis of the noncontiguous polypropionate dolabriferol C was achieved by retro-Claisen fragmentation of its putative contiguous precursor under mild conditions, thus establishing the former as a plausible isolation artifact. The precursor was prepared by a novel one-pot three-component bisaldol coupling of a meso (Z,Z)-bisenolate (generated in situ from a 3,7-diketone) with two enantioenriched aldehydes to set the absolute configuration of seven stereocenters in one step. The first aldol reaction proceeded with enantioselective desymmetrization of the bisenolate to produce an enantiomerically pure enolate-aldolate. Quenching at this stage enabled a streamlined synthesis of dolabriferol. Addition of a racemic aldehyde to the enolate-aldolate resulted in aldol coupling with kinetic resolution of the ""matched"" aldehyde; overall, a sequential enantiotopic-group-selective (SEGS) bisaldol reaction. Because the desired adduct results from the ""mismatched"" aldol reaction, use of enantioenriched aldehyde was required.",10.1002/anie.202111895,2021-10-15,0.598922404139074
Organic Process Research & Development,What Does It Take to Develop Structurally Complex Molecules by Total Synthesis? Rapid Process Development and GMP Manufacturing of E7130 Drug Substance for First-in-Human Clinical Study,"Process development of E7130 Drug Substance, which is a novel anticancer drug candidate, is described. To accomplish rapid delivery of such a large and structurally complex drug substance for first-in-human (FIH) clinical trial, close collaboration among medicinal chemistry, process chemistry, and academia teams was required. The successful establishment of a suitable synthetic route in a concise time frame while negotiating challenging chemical reactions (e.g., asymmetric catalytic Nozaki–Hiyama–Kishi (NHK) reaction and Zr/Ni-mediated ketone coupling reaction) is described herein. Experience with the development of eribulin mesylate was helpful in anticipating and overcoming the chemical and logistical challenges encountered in the E7130 project. Based on this background, more than 10 g of E7130 Drug Substance has been successfully manufactured under Good Manufacturing Practice (GMP) controls within 1.5 years after the medicinal chemistry team succeeded in the first total synthesis.",10.1021/acs.oprd.4c00016,2024-04-15,0.5989194900370677
Organic Letters,Chiral Pool Based Efficient Synthesis of the Aminocyclitol Core and Furanoside of (−)- Hygromycin A: Formal Total Synthesis of (−)-Hygromycin A,A chiral pool based synthetic strategy that leads from the readily available and inexpensive C(2)-symmetric tartaric acids to the chiral O-isopropylidenebenzooxazole--a convenient precursor to the aminocyclitol core of hygromycin A as well as the chiral γ-disilyloxybutyrolactone--a pivotal intermediate to approach to the furanoside of hygromycin A.,10.1021/ol3028237,2012-11-13,0.5989174388593493
Synthesis,"Synthesis of Conformationally Constrained Spirohydantoins with a Dibenzo[a,d]heptadiene Ring","All articles of this category Conformationally constrained dibenzo[ a,d ]cycloheptadiene-based spirohydantoins were prepared from dibenzosuberone via the transformation of the α -hydroxy ester to the azido ester, followed by its reduction to the amino ester, and cyclization of the carbomethoxy N,N ′-asymmetric ureas, derived from the amino ester with triphosgene and a variety of amines. A novel ring expansion reaction was also observed in the process. spirohydantoins - triphosgene - N,N ′-asymmetric ureas - 6-carbomethoxy-11,12-dihydrodibenz[ b,f ]azocine - ring expansion reaction",10.1055/s-2000-7108,2000-01-01,0.5989146869398904
Tetrahedron,Asymmetric synthesis of a highly functionalized β-amino acid: the key amino acid of sperabillins B and D,,10.1016/s0040-4039(99)01954-1,1999-12-01,0.5989094059122018
Journal of Organic Chemistry,A Synthesis of (±)-Stemodinone:  An Application of Organoiron Chemistry to the Construction of Sterically Congested Quaternary Carbon Centers,"A synthesis of racemic stemodinone is described, using tricarbonyl(1−5-η-4-methoxy-1,3-dimethylcyclohexadienyl)iron(I) hexafluorophosphate ( 9 ) as an electrophile that is the A-ring precursor. Reaction of 9 with the tin enolate from 4,4-(ethylenedioxy)cyclohexanecarbaldehyde proceeded with excellent regioselectivity and high yield to generate an intermediate representing the A and C rings of the target molecule. The B ring was constructed by introducing a two-carbon electrophilic group onto the A ring, followed by ring closure using an intramolecular enolate alkylation. Installation of the D ring and manipulation to give the final product followed transformations precedented with this series of compounds.",10.1021/jo9705475,1997-08-01,0.5989060286118091
Angewandte Chemie International Edition,Rhodium‐Catalyzed Asymmetric Synthesis of β‐Branched Amides,"A general asymmetric route for the one-step synthesis of chiral β-branched amides is reported through the highly enantioselective isomerization of allylamines, followed by enamine exchange, and subsequent oxidation. The enamine exchange allows for a rapid and modular synthesis of various amides, including challenging β-diaryl and β-cyclic.",10.1002/anie.201610500,2016-12-27,0.598901470485775
Organic Letters,Stereoselective Synthesis of Macrolide-Type Antibiotics from Epoxy Amides. Synthesis of the Polypropionate Chain of Streptovaricin U,The synthesis of the polypropionate chain of Streptovaricin U (1) is described utilizing a new approach for the stereoselective synthesis of the macrolide-type antibiotics via sulfur ylides.,10.1021/ol7022938,2007-11-01,0.5989007218603609
Journal of Organic Chemistry,Asymmetric Total Synthesis of the 1-<i>e</i><i>pi</i>-Aglycon of the Cripowellins A and B,"[structure: see text] The unusual [5.3.2]-bicyclic structure of the insecticidal Amaryllidaceae alkaloids cripowellin A (1) and B (2) has been synthesized for the first time via a sequence of Sharpless dihydroxylation, ring-closing metathesis, and intramolecular Heck reaction. The asymmetric synthesis of the 1-epi-aglycon 82 proceeds with virtually complete diastereo- and enantioselectivity (de, ee > or = 98%) in 13 steps and an overall yield of 5.6%. In addition, three alternative approaches toward the aglycon 3 are also described focusing on (1) the alkylation of the 2-benzazepinedithianes 35 and 36 with the electrophile 11, (2) a radical cyclization of the precursor (R/S,S,S)-39, and (3) an intramolecular arylation reaction of the aryl ketone 47.",10.1021/jo0518093,2005-11-12,0.5989001948577897
Tetrahedron,A general and efficient route to 3-amino-4-sulfanylcoumarins via substitution and palladium-catalyzed amination of 3-bromo-4-tosyloxycoumarins,,10.1016/j.tetlet.2007.03.142,2007-03-31,0.5988982893735201
Synlett,"A Short Synthesis of a Trifold Orthogonally Protected, Novel Aminoazepanol Building Block","Orthogonally protected cis-5-aminoazepan-3-ol derivatives were prepared in three steps from N-Boc allylic amine, acrolein, and N-benzylhydroxylamine with an intramolecular 1,3-dipolar cycloaddition as the key reaction.",10.1055/s-0031-1289564,2011-10-31,0.5988954584870737
European Journal of Organic Chemistry,"Synthesis of (1′<i>R</i>,3<i>S</i>,4<i>S</i>)‐3‐[1′‐(<i>tert</i>‐Butyldimethylsilyloxy)ethyl]‐ 4‐(cyclopropylcarbonyloxy)azetidin‐2‐one","Abstract The novel carbapenem precursor 1e has been synthesized from L ‐threonine, cyclopropyl methyl ketone and benzhydrylamine (for the introduction of the azetidinone N ‐protecting group). Two independently prepared building blocks – sodium (2 R ,3 R )‐2,3‐epoxybutyrate as a mixed salt with NaBr ( 2b ) and N ‐(benzhydryl)aminomethyl cyclopropyl ketone ( 4e ) – were coupled to give (2 R ,3 R )‐ N ‐(benzhydryl)‐ N ‐(2‐cyclopropyl‐2‐oxoethyl)‐2,3‐epoxybutyramide ( 8e ). This key intermediate gave a regio‐ and stereoselective C3–C4 ring closure on LiHMDS treatment in THF at 0 °C to yield(1′ R ,3 S ,4 S )‐4‐cyclopropylcarbonyl‐1‐diphenylmethyl‐3‐(1‐hydroxyethyl)azetidin‐2‐one ( 13e ). N ‐Deprotection of 13e was performed by photochemical bromination and subsequent hydrolysis. The resulting (1′ R ,3 S ,4 S )‐4‐(cyclopropylcarbonyl)‐3‐(1‐hydroxyethyl)azetidin‐2‐one ( 23e ) reacted in a Baeyer–Villiger oxidation with a total control of the regioselectivity (due to the poor migratory aptitude of the cyclopropyl group) to furnish (1′ R ,3 S ,4 S )‐3‐(1‐hydroxyethyl)‐4‐(cyclopropylcarbonyloxy)azetidin‐2‐one ( 24e ), subsequent O ‐silylation achieving the total synthesis of 1e (title compound).(© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2006)",10.1002/ejoc.200600235,2006-06-14,0.5988901798214222
Journal of Organic Chemistry,"Synthesis of α-Phosphorylated α,β-Unsaturated Imines and Their Selective Reduction to Vinylogous and Saturated α-Aminophosphonates","An efficient synthesis of alpha,beta-unsaturated imines derived from alpha-aminophosphonates is achieved through aza-Wittig reaction of P-trimethyl phosphazenes with beta,gamma-unsaturated alpha-ketophosphonates. Selective 1,2-reduction of such 1-azadienes affords beta,gamma-unsaturated alpha-aminophosphonates, phosphorylated analogs of vinylglycines, which are hydrogenated to yield saturated alpha-aminophosphonate derivatives.",10.1021/jo062609+,2007-03-01,0.5988896610289234
Journal of Organic Chemistry,"Total Synthsis of (+)-Ambuic Acid: α-Bromination with 1,2-Dibromotetrachloroethane","Total synthesis of (+)-ambuic acid has been accomplished from the readily available stereocontrolled Diels-Alder adduct of cyclopentadiene and iodo-1,4-benzoquinone monoketal through an efficient series of steps. A new method for the highly commendable synthesis of α-brominated Diels-Alder adduct is described.",10.1021/jo202357s,2012-01-25,0.5988806309730962
Organic Process Research & Development,Redesign of the Synthesis and Manufacture of an Azetidine-Bearing Pyrazine,Commercial route definition for a glucokinase activator called for a re-evaluation of the synthesis and processes used to access multikilogram quantities of a pyrazine building block. The processes developed allowed a literature route to sodium 6-oxo-1 H -pyrazine-3-carboxylate to be leveraged. One of these processes consisted of a highly selective decarboxylation that allowed the target building block to be accessed with complete regioselectivity in standard batch processing equipment. The presence of an azetidine ring in the target required the mitigation of impurity liabilities arising from the use of the hydrochloride salt of azetidine as an input material.,10.1021/acs.oprd.7b00384,2018-01-18,0.5988778205028525
Journal of the American Chemical Society,Collaborative Total Synthesis: Routes to (±)-Hippolachnin A Enabled by Quadricyclane Cycloaddition and Late-Stage C–H Oxidation,"Described herein are synthetic efforts toward the synthesis of hippolachnin A. Two independently devised routes from the Brown and Wood groups allowed for the synthesis of hippolachnin A from the unusual starting material, quadricyclane, by harnessing the power of late-stage C-H oxidation. Collaborative union of the best features of the two routes allowed for preparation of the molecule with improved efficiency.",10.1021/jacs.5b13586,2016-02-09,0.598877248055735
Journal of the American Chemical Society,Asymmetric Synthesis of A-240610.0 via a New Atropselective Approach for Axially Chiral Biaryls with Chirality Transfer,"A new approach for atropselective preparation of axially chiral biaryl was developed. This process proceeded through a chirality transfer from a stereogenic center of a secondary alcohol to the stereogenic axis via regioselective intramolecular silyl group migration. This methodology allowed for the preparation of a single atropisomer 2 in good yield (85%) with high diastereoselectivity (99:1), which subsequently led to the successful development of an efficient asymmetric synthesis of A-240610.0, 1.",10.1021/ja0171198,2002-03-23,0.5988605545772527
Journal of the American Chemical Society,"Biogenetically Inspired Total Syntheses of <i>Lycopodium</i> Alkaloids, (+)-Flabellidine and (−)-Lycodine","The first asymmetric total synthesis of (+)-flabellidine (2) and the shortest total synthesis of (-)-lycodine (3) were accomplished by a strategy featuring the one-pot construction of a tetracyclic lycodine skeleton from a linear precursor, which was inspired by the biosynthetic consideration of Lycopodium alkaloids.",10.1021/ja507016g,2014-08-08,0.5988445383527151
European Journal of Organic Chemistry,"Synthesis of 2,5‐Disubstituted Pyridines using the Gold(I)‐Catalyzed Cycloisomerization of 1‐Bromoalkynes as Key Step","Abstract Gold‐catalyzed cycloisomerization reaction of 1‐bromoalkynes allowed for the preparation of a variety of 1‐bromocyclopentene derivatives. These have been used as substrates in a 3‐step synthetic sequence comprising a cross‐coupling reaction, followed by ozonolysis, and final condensation towards the corresponding 2,5‐disubstituted pyridine. In addition, bicyclic fused pyridines are achieved, including the first total synthesis of the natural product Sinensine B.",10.1002/ejoc.202301274,2023-12-18,0.5988426619872251
Journal of Organic Chemistry,Synthesis of an Aminooxy Derivative of the Tetrasaccharide Repeating Unit of <i>Streptococcus dysgalactiae</i> 2023 Polysaccharide for a PS A1 Conjugate Vaccine,A highly efficient and stereocontrolled synthesis of an aminooxy derivative of the tetrasaccharide repeating unit of a rhamnose-rich polysaccharide isolated from the cell envelop of bovine mastitis Streptococcus dysgalactiae 2023 is reported for the first time. The synthesis was accomplished utilizing a stereoselective and convergent [2 + 2] glycosylation strategy inclusive of a disaccharide Schmidt donor and an inclusive rhamnose disaccharide acceptor. The synthetic aminooxy tetrasaccharide was conjugated to T-cell stimulating immunogen PS A1 from Bacteroides fragilis ATCC 25285/NCTC 9343 via a physiologically stable oxime linkage to furnish the first semisynthetic bacterial-based immunogen construct targeting S. dysgalactiae 2023. The synthetic tetrasaccharide was assembled in 19 steps with a ∼5.0% overall yield.,10.1021/acs.joc.6b00195,2016-05-05,0.5988416230361941
Tetrahedron,An improved stereoselective total synthesis of (R)-rugulactone,,10.1016/j.tetlet.2011.07.109,2011-08-02,0.5988286606144989
Organic Process Research & Development,Building Efficient Diastereo- and Enantioselective Synthetic Routes to <i>trans-</i>Cyclopropyl Esters for Rapid Lead Scale-Up,"High Resolution Image Download MS PowerPoint Slide Cyclopropanes play an important role in drug discovery, and synthetic access to variedly substituted systems is an ongoing challenge for chemistry teams. A variety of scalable synthetic routes were developed and optimized for the construction of 1,2-trans-disubstituted cyclopropyl esters. The use of a stable cyclopropyl trifluoroborate provided a path for the rapid exploration of heteroaryl substituent diversity. Two asymmetric approaches were subsequently enabled as viable alternatives. Our first approach led to the development of a novel sulfoximine-driven Johnson–Corey–Chaykovsky reaction of menthyl acrylates and is the first example of this chemistry for the enantio- and diastereostereoselective construction of trans-cyclopropanes. Ultimately, a scalable process route was fashioned through the optimization of an efficient ring opening/intramolecular C–O phosphate transfer and displacement cascade that builds the trans-cyclopropyl ester from a chiral epoxide with excellent stereocontrol.",10.1021/acs.oprd.5c00007,2025-03-03,0.5988122026555809
Synthesis,"New Synthesis of 1,5-Disubstituted Imidazoles",All articles of this category A new synthesis of 1-alkylimidazole-5-carbaldehydes starting from [3-(dimethylamino)-2-azaprop-2-enylidene]dimethylammonium chloride and alkyl N -alkylglycinate is described.,10.1055/s-1994-25449,1994-01-01,0.5988021127041441
Synthesis,Chemoenzymatic Total Synthesis of (+)-Oxycodone from Phenethyl Acetate,"The stereoselective total synthesis of unnatural (+)-oxy­codone from phenethyl acetate is described. Absolute stereochemistry was established via microbial dihydroxylation of phenethyl acetate with the recombinant strain JM109 (pDTG601A) to the corresponding cis-cyclohexadienediol­ whose configuration provides for the absolute stereo­chemistry of the ring C of (+)-oxycodone. Intramolecular Heck cyclization was employed to establish the quaternary carbon at C-13, along with the dibenzodihydrofuran functionality. The C-14 hydroxyl was installed via SmI2-mediated radical cyclization. The synthesis of (+)-oxy­codone was completed in a total of 13 steps and an overall yield of 1.5%. Experimental and spectral data are provided for all new compounds.",10.1055/s-0037-1611335,2018-11-20,0.5987891464813078
Tetrahedron,"Cu(OTf)2-promoted efficient synthetic route towards glycospiro-pyrrolo[2,1-a]isoquinolines",,10.1016/j.tetlet.2014.08.076,2014-09-05,0.5987876607441994
Tetrahedron,Efficient synthesis of N-arylpiperazinones via a selective intramolecular Mitsunobu cyclodehydration,,10.1016/s0040-4039(98)01670-0,1998-10-01,0.5987844354767514
Synlett,Highly Efficient Synthesis of Polysubstituted 2-Aminopyrroles via a Multicomponent Domino Reaction,"A highly efficient approach to polysubstituted 2-amino­pyrroles containing a coumarin derivative unit at the 5-position of the pyrrole ring was developed via a novel multicomponent domino reaction of glyoxal monohydrate derivatives, anilines, coumarin derivatives, and malononitrile. This transformation proceeded via an α-amino­ketone as the key intermediate.",10.1055/s-0036-1591907,2018-02-15,0.5987781539183165
Journal of Organic Chemistry,"Palladium-Catalyzed Asymmetric Allylic Substitution of 2-Arylcyclohexenol Derivatives:  Asymmetric Total Syntheses of (+)-Crinamine, (−)-Haemanthidine, and (+)-Pretazettine","Much interest has been shown in Amaryllidaceae alkaloids as synthetic targets due to their wide range of biological activities. Over 100 alkaloids have been isolated from members of the Amaryllidaceae family; most of them can be classified into eight skeletally homogeneous groups. We have succeeded in the first asymmetric total syntheses of the crinane-type alkaloids (+)-crinamine (1), (-)-haemanthidine (2), and (+)-pretazettine (3). The starting cyclohexenylamine 14 was obtained from allyl phosphonate 11c by palladium-catalyzed asymmetric amination in 82% yield and with 74% ee. The product was recrystallized from MeOH. Interestingly, (-)-14 with 99% ee was obtained from the mother liquor (74% recovery). Intramolecular carbonyl-ene reaction of (-)-10 proceeds in a highly stereoselective manner to give hexahydroindole derivative 9 as the sole product. In the Lewis-acid-catalyzed carbonyl-ene reaction, an interesting rearrangement product, 20, was isolated in high yield. From 9, (+)-crinamine was synthesized. Thus, the asymmetric total synthesis of (+)-crinamine was achieved in 10 steps from 11c, and the overall yield is 19%. The total synthesis of (-)-haemanthidine was also achieved from 9 by a short sequence of steps.",10.1021/jo030309b,2004-02-14,0.5987769597463893
Angewandte Chemie International Edition,Strategies for the Synthesis of Fusicoccanes by Nazarov Reactions of Dolabelladienones: Total Synthesis of (+)‐Fusicoauritone,Attaining closure: A synthetic pathway leading to (+)-fusicoauritone (1) is highlighted by the use of a Julia condensation for preparation of an eleven-membered-dolabelladienone precursor for subsequent Nazarov cyclization to yield the 5-8-5 tricyclic diterpene skeleton.,10.1002/anie.200603853,2006-12-15,0.5987756094277057
Synthesis,"An Improved, Versatile, and Easily Scalable Synthesis of Sphingomyelins: Application to Stable Isotope Labeling","With a view to make conveniently labeled mass spectrometry standards available, a set of deuterated sphingomyelins were prepared by a new expedient, flexible, robust, scalable, and high-yielding synthetic scheme starting from 2-azido-3-O-benzoylsphingosine as the key intermediate. Unlike previously published procedures, this work emphasizes the benefit arising from the choice of the azido function as a masking group for the reactive primary amine during the troublesome, though crucial, phosphorylation step.",10.1055/s-0039-1690863,2020-03-24,0.5987721096592981
Synthesis,"First Total Synthesis and Investigation of the X-ray Crystal Structure of the Pyrano[3,2-a]carbazole Alkaloid Clausenalansine A","Abstract We describe the first total synthesis of the recently discovered pyrano[3,2-a]carbazole alkaloid clausenalansine A. The synthetic strategy for the construction of this formylpyrano[3,2-a]carbazole is based on a sequence of Buchwald–Hartwig coupling, palladium(II)-catalyzed oxidative cyclization, Lewis acid promoted annulation of the pyran ring, and chemoselective oxidation of a methyl to a formyl group.",10.1055/s-0040-1706551,2020-11-05,0.5987678356818823
Journal of Organic Chemistry,"Birch Reduction of (−)-Ephedrine. Formation of a New, Versatile Intermediate for Organic Synthesis","The reduction of (-)-ephedrine by lithium in liquid ammonia resulted in the formation of S-1-(1,4-cyclohexadien-1-yl)-N-methyl-2-propanamine. In addition to the reduction of the aromatic ring, the hydroxy group was reduced as well. The resulting 1,4-cyclohexadienyl group is a potentially versatile intermediate for further synthetic transformations. The ozonolysis of this group was investigated, producing derivatives of beta-keto-delta-methylamino esters and beta-keto aldehydes which could be subsequently converted to heterocycles. The restriction to rotation of the C-N bond in N-benzoyl-1-(1,4-cyclohexadien-1-yl)-N-methyl-2-propanamine is described.",10.1021/jo049726u,2004-07-08,0.5987670990404175
Journal of Organic Chemistry,Synthesis of <scp>l</scp>-Iduronic Acid Derivatives via [3.2.1] and [2.2.2] <scp>l</scp>-Iduronic Lactones from Bulk Glucose-Derived Cyanohydrin Hydrolysis: A Reversible Conformationally Switched Superdisarmed/Rearmed Lactone Route to Heparin Disaccharides,"L-Idofuranoside cyanohydrin 1 is converted on large scale into a mixture of L-IdoA methyl pyranosides and furanosides, which is converged to provide short 2-step routes to bicyclic [3.2.1] or [2.2.2] L-iduronate lactones. The former is obtained via a 100 g scale synthesis of 3-OBn L-IdoA. A two-step conversion of this mixture provides either pure anomer of the novel [2.2.2] l-iduronate thioglycoside lactones. Both [3.2.1] and [2.2.2] lactones are converted into GlcN-IdoA heparin precursor disaccharides. The [2.2.2] lactone enables a scalable 3-step route from 1 to a new type of highly disarmed O-4 iduronate thioglycoside, which is an effective acceptor with glucoazide thioglycoside donors. The resulting new iduronic [2.2.2] lactone disaccharides are readily rearmed by mild methanolysis to provide GlcN-IdoA thiophenyl disaccharide donors, intercepting their established utility for the assembly of both heparin- and heparan sulfate-like oligosaccharides. The [2.2.2] lactonization acts as a conformational switch to superdisarm iduronate components, reversible by lactone ring opening. In addition, the separated 2,4-diacetates also provide short access to all four anomeric and ring size isomers of l-iduronic acid methyl glycosides, including the first syntheses of the parent idofuranosides. X-ray structures are reported for a [2.2.2] iduronate lactone and examples of both methyl L-idopyranoside and novel methyl-L-idofuranoside systems.",10.1021/jo502776f,2015-02-03,0.5987503316753847
Synthesis,Preparative Route to Per-O-acetylated<i>N</i>-Acetyl- and<i>N</i>-(<i>tert</i>-Butoxycarbonyl)neuraminyl-α-(2→3)-galactosyl Disaccharide Glycosyl Donors by Regioselective Acetolysis of Sialyl-α-(2→3′)-lactose,"Per-O-acetylated N-acetylneuraminyl-α-(2→3)-galactopyranose was prepared in three steps in good overall yield from sialyl-α-(2→3′)-lactose by regioselective cleavage of the galactosyl-β-(1→4)-glucose linkage by acetolysis and then readily converted into the corresponding disaccharide 1-trichloroacetimidate or ethyl thioglycoside, valuable synthetic blocks for the preparation of complex sialylated oligosaccharides. The N-acetyl group in the disaccharide thioglycoside was replaced by an N-Boc one via intermediate formation of a mixed N-Ac-N-Boc imide followed by chemoselective de-N-acetylation with hydrazine hydrate in DMF. An example of application of the disaccharide thioglycoside for the preparation of a spacer-armed hexasaccharide SLex is described.",10.1055/s-2005-869957,2005-01-01,0.5987429583220869
Journal of Organic Chemistry,Studies toward the Total Synthesis of Nogalamycin: Construction of the Complete ABCDEF-Ring System via a Convergent Hauser Annulation,"The convergent synthesis of the complete ABCDEF-ring system within nogalamycin, an anthracycline natural product, was studied. The pivotal Hauser annulation for the anthraquinone core construction was achieved by the fusion of two highly functionalized segments: a cyanophthalide (the AB-ring segment) and a tricyclic quinone monoketal (the DEF-ring segment). Key transformations toward the AB-ring segment include an enantioselective enolate α-hydroxylation, a diastereoselective hydroboration-oxidation, and a directed aromatic lithiation-formylation. To prepare the DEF-ring segment for annulation, a mild dearomatization of the F-ring phenol group by (diacetoxyiodo)benzene (PIDA) was employed.",10.1021/acs.joc.8b02602,2018-12-25,0.5987424815120449
Angewandte Chemie International Edition,"Studies toward the Synthesis of Azadirachtin, Part 1: Total Synthesis of a Fully Functionalized ABC Ring Framework and Coupling with a Norbornene Domain",The advanced decalin intermediate 1 was synthesized and elaborated into the potential azadirachtin precursor 2. The challenging synthesis involved several protecting-group manipulations and coupling of 1 with an appropriate norbornene unit.,10.1002/anie.200500216,2005-04-21,0.5987392637697958
Tetrahedron,A novel synthesis of amino acid derivatives of phospholene oxides,,10.1016/j.tetlet.2004.05.091,2004-06-12,0.5987332749088927
Tetrahedron,Synthesis of (4E)-7-methoxytetradec-4-enoic acid: a novel fatty acid from lyngbya majuscula,,10.1016/s0040-4039(00)74202-x,1992-04-01,0.5987262267270587
Tetrahedron,Synthetic approach to the total synthesis of fumitremorgins II synthesis of optically active pentacyclic intermediates and their dehydrogenation,,10.1016/s0040-4039(00)84762-0,1986-01-01,0.5987261607448165
Organic Letters,Total Synthesis of (−)-Callystatin A,"[reaction: see text] The enantioselective synthesis of callystatin A is described. The pivotal step in the synthesis is the stereoselective aldol reaction that generates the beta-hydroxy ketone moiety. Utilizing the allylic strain within the ethyl ketone precursor, we were able to generate the all-syn configuration of callystatin A. For the construction of the two diene moieties, both a Heck coupling and a Wittig reaction were employed.",10.1021/ol016365l,2001-09-07,0.5987234802166863
Journal of Organic Chemistry,"Divergent Synthesis of the Co-isolated Mycotoxins Longianone, Isopatulin, and (<i>Z</i>)-Ascladiol via Furan Oxidation","Longianone and the biosynthetically related mycotoxins isopatulin and (Z)-ascladiol were prepared following a divergent route from a readily available furan diol. The route toward longianone features an unprecedented TBAF-promoted intramolecular oxa-Michael reaction to a conjugated keto enoate, and the oxidation of dihydrolongianone to longianone with stabilized IBX. The route to isopatulin features a chemoenzymatic synthesis of (Z)-ascladiol, and the regioselective oxidation of (Z)-ascladiol to isopatulin with MnO(2).",10.1021/jo900855e,2009-08-14,0.5987217742348439
Organic Letters,Synthesis of Highly Substituted Azepanones from 2<i>H</i>-Azirines by a Stepwise Annulation/Ring-Opening Sequence,"Bicyclic aziridines possessing a 1-azabicyclo[4.1.0]heptan-2-one core were prepared from 2 H-azirines by a stepwise annulation sequence involving a diastereoselective allylindanation, an N-acylation, and a ring-closing metathesis to construct the six-membered ring. After hydrogenation or functionalization of the olefin, regioselective ring opening of the resulting azabicyclic compounds with carboxylic acids (or sulfur nucleophiles) afforded highly substituted azepanones possessing an ester moiety or a trifluoromethyl group and a tetrasubstituted carbon at the α and β positions of the nitrogen atom, respectively.",10.1021/acs.orglett.9b00999,2019-04-26,0.5987214997334643
Synlett,Total Synthesis of (±)-Phytochromobilin Starting from Two Pyrrole Derivatives,"All articles of this category (±)-Phytochromobilin was synthesized as an acid form by developing a convenient method for the preparation of A- and D-rings starting from a 2-tosylpyrrole derivative, followed by efficient construction of A/B- and C/D-ring components via Wittig-type coupling reaction of 5-tosylpyrrolinones with 2-formylpyrrole, and palladium catalyzed deprotection of allyl esters of propanoic acid side chains of C-8 and C-12. phytochrome - tetrapyrrole - phytochromobilin - total synthesis - transformation of pyrroles",10.1055/s-1999-3105,1999-12-31,0.5987162598907195
Organic Letters,"A Highly Regioselective Sonogashira Coupling as a Key Step in the Preparation of the First Phenanthroline with Two Diverse Reactive Groups in 3,8-Positions","The preparation of 3,8-unsymmetric phenanthrolines is described. Desymmetrization of 3,8-dibromophenanthroline was achieved after monoarylation followed by regioselective Pd-catalyzed monoalkynylation that was controlled by the methoxy group of the dimethoxyphenyl substituent.",10.1021/ol006514k,2000-11-11,0.598714772739091
Journal of Organic Chemistry,Total Synthesis and Antifungal Activity of a Carbohydrate Ring-Expanded Pyranosyl Nucleoside Analogue of Nikkomycin B,"In a study aimed at investigating an as yet unknown structure-activity relationship of the nikkomycin family of antifungal peptidyl nucleoside antibiotics, the present research reports the synthesis and antifungal evaluation of a carbohydrate ring-expanded pyranosyl nucleoside analogue of nikkomycin B. Employing a convergent synthetic route, independent synthesis of the N-terminal amino acid side chain and a stereoselective de novo construction of the desired pyranosyl nucleoside amino acid fragment was followed by peptidic coupling of the two components, leading to the first synthesis of a carbohydrate ring-enlarged pyranosyl nikkomycin B analogue. In vitro biological evaluation of the above analogue against a variety of human pathogenic fungi demonstrated significant antifungal activity against several fungal strains of clinical significance.",10.1021/jo701814b,2007-11-15,0.5987071446314001
Organic Process Research & Development,A Practical Synthesis of an Anti-Methicillin Resistant <i>Staphylococcus</i> <i>aureus</i> Cephalosporin BMS-247243,"A practical synthesis of the anti-methicillin resistant Staphylococcus aureus cephem (6 R - trans )- E -7-[[[[2,5-dichloro-4-[3-[(carboxymethyl)amino]-3-oxo-1-propenyl]phenyl]-thio]-acetyl]amino]-4-[[(2-carboxy-8-oxo-5-thia-1-azabicyclo-[4.2.0]oct-2-en-3-yl)methyl]thio]-2,6-dimethyl-1-[3-(4-methylmorpholino-4-yl)propyl]-1-pyridinium, hydroxide, inner salt (BMS-247243) was developed. A process was developed for the interchange of the iodide counterion in 3a to chloride 3b that was essential for an efficient synthesis of the C-3 side chain 4-mercaptopyridone 6b . Use of catalytic Bu 4 NCl in the reaction of chlorocinnamide 14 with the Li-salt of methylthioglycolate formed the methyl ester of the C-7 side chain 12b in high yield. Reaction with the dianion of thioglycolic acid gave an increased level of the corresponding Michael addition byproduct that led to lower quality thermodynamic product 12b by the reverse reaction. Cephem nucleus 16 was acylated with the acid chloride of acid 12b in a biphasic system to circumvent the cumbersome workup involved in reactions mediated by carbodiimdes DCC or EDAC for the synthesis of diester 17 . An unusual degradation product diacid 20 was obtained during the deprotection of diester 17 with TFA to amorphous diacid 19 . Reaction of diacid 19 with 4-mercaptopyridone 6b formed BMS-247243 in moderate yield. Alternately, an efficient coupling of diester 17 with 4-mercaptopyridone 6b gave crystalline diester 21 with minimal (<1%) contamination of the double bond isomer 22 . Double deprotection of diester 21 followed by crystallization furnished the double zwitterion BMS-247243 in high yield.",10.1021/op0002850,2000-09-15,0.598702025362777
Synlett,"Synthesis of Bistramide A and Analogues, Part 1: Stereoselective Access to Normethyl Tetrahydropyran Subunit","A stereoselective synthesis of normethyl C1-C13 fragment of bistramide A is described. The key steps involve an asymmetric Sharpless epoxidation, a cross-metathesis reaction and an intramolecular oxa-Michael reaction. The trans-2,6-disubstituted tetrahydropyran subunit has been synthesized in an overall yield of 7% with 96% ee. The cis isomer was prepared by a similar pathway with the same efficiency and enantioselectivity.",10.1055/s-2008-1072714,2008-04-25,0.5986988473406073
Journal of Organic Chemistry,Radical-Based Route to Functionalized Tetralin: Formal Total Synthesis of (±)-Hamigeran B,"A formal synthetic route to hamigeran B, an antiviral marine natural product with a unique tricyclic molecular architecture, has been developed. The key chemical transformations in the present route include a novel zinc(II)porphyrin-catalyzed photoredox radical cascade cyclization to access a functionalized tetralin, a catalyst-free benzylic radical bromination with NBS by visible-light irradiation, and a samarium(II)-induced cyclization of brominated tetralone possibly via an orthoquinodimethane-like intermediate.",10.1021/acs.joc.2c02552,2023-01-10,0.5986985866286645
Organic Letters,Total Synthesis and Stereochemical Revision of (+)-Aeruginosin 298-A,"[structure:see text] Novel routes toward both enantiomers of the bicyclic proline surrogate 2-carboxy-6-hydroxyoctahydroindole, i.e., Choi, were developed on the basis of the oxidative cyclization of L-tyrosine. Synthesis of the proposed sequence of (+)-aeruginosin 298-A did not provide the natural product. Incorporation of a D-leucine residue, in contrast, led to the total synthesis of this thrombin inhibitor.",10.1021/ol006759x,2000-11-28,0.5986942604907455
Synlett,"Studies on Fluorinated Annulated Nicotines: Concise Synthesis of cis-4,4-Difluoro-2,3,3a,4,5,9b-hexahydro-1-methyl-1H-pyrrolo[2,3-f]quinoline","A fused 6,6,5-tricyclic difluorinated nicotine analogue was efficiently assembled in five steps in 36% overall yield. The conformation-restricting unit is a six-membered fluorinated carbocycle. The gem-difluoromethylene group was introduced through an indium-promoted Barbier allylation of 3-bromo-3,3-difluoropropene. The construction of the tricyclic skeleton was achieved using an intramolecular azomethine ylide-alkene [3+2] cycloaddition.",10.1055/s-0029-1217519,2009-06-25,0.5986921640654392
Synthesis,"Asymmetric Synthesis of 2-(α-Aminoalkyl)oxazoles, 2-Oxazolylpyrrolidines, 2-Oxazolylpiperidines: Total Synthesis of 4,5-Dihydroxypipecolinic Acid","All articles of this category Asymmetric α -alkylation of 2-aminomethyl-4,5-diphenyloxazole was achieved by formation of azomethines 1 and ent - 1 with the enantiomers of 2-hydroxypinan-3-one as chiral auxiliaries, reaction with alkylating reagents and final removal of the chiral auxiliary giving rise to optically active 2-( α -aminoalkyl)oxazoles 3 , ent - 3 , 6 and 9 . If α , ω -dihaloalkanes were used the resulting alkylation products could be further cyclized by intramolecular alkylation of the amino group to afford optically active 2-oxazolyl- N -heterocycles 4 , ent - 4 , 7 and 10 . The latter could be used for the total synthesis of naturally occurring 4,5-dihydroxypipecolinic acid 13 . 2-(1-aminoalkyl)-1,3-oxazoles - asymmetric synthesis - 2-oxazolylpiperidines - 2-oxazolylpyrrolidines - 4,5-dihydroxypipecolinic acid - chiral auxiliaries - heterocycles",10.1055/s-2000-8719,2000-01-01,0.5986895955426772
Tetrahedron,"Dehydrohalogenation of the bis-dichlorocarbene adducts of some cyclohexa-1,4-dienes: a regiospecific route to homotropilidenes",,10.1016/s0040-4039(01)95359-6,1979-01-01,0.598688583714065
Synthesis,"Bromination of α-Aroylketene<i>S,S</i>-Acetals: Synthesis of Novel α-Aroyl-α-bromoketene<i>S,S</i>-Acetals and Their Further Synthetic Transformations",,10.1055/s-1985-31141,1985-01-01,0.5986849298618594
Organic Letters,Design and Synthesis of Novel Conformationally Restricted Peptide Secondary Structure Mimetics,[structure: see text] A facile synthesis of the novel conformationally restricted reverse turn mimetic is described. The key features are the preparation of the alpha-keto amide and tandem bicyclic ring formation.,10.1021/ol990355r,2000-01-11,0.5986822405921762
Organic Letters,Total Synthesis of (−)-Salicylihalamide A,"[see structure]. A 16-step synthesis of the novel cytotoxin salicylihalamide A (1E) has been achieved in 3.3% overall yield using ring closing metathesis to generate the macrolide and addition of (1Z,3Z)-hexadienylcuprate (2), which was generated in situ from ethylcuprate and acetylene, to alkenyl isocyanate 3 to form the side chain.",10.1021/ol015822v,2001-05-18,0.5986789504402403
Synthesis,"A Convenient Method for Synthesis of Novel 3-(1,3,4-Oxadiazol-2-yl)-methylene-2-oxo-1,2,3,4-tetrahydroquinoxalines: Regioselective Cyclization of 3-Ethoxyhydrazonocarbonylmethylene-2-oxo-1,2,3,4-tetrahydroquinoxaline",,10.1055/s-1983-30299,1983-01-01,0.5986629278947764
Synthesis,Efficient Synthesis of Diphenyl<b><i>ketene</i></b>-<sup>¹³</sup>C<sub>2</sub>,"A short and efficient synthesis of doubly ¹³ C labeled diphenylketene from relatively cheap ¹³ C labeled carbon dioxide, as the sole source of labeled carbon, is described in 22% overall yield.",10.1055/s-2001-18702,2002-07-26,0.5986588394375506
Tetrahedron,A synthesis of (−)-tashiromine and formal synthesis of (+)-tashiromine utilizing a highly enantioselective pyrrole/cobaloxime π-cation cyclization,,10.1016/s0040-4039(97)01638-9,1997-10-01,0.5986568668334079
Synlett,Facile Route to TetrasubstitutedPyrazoles Utilizing Ceric Ammonium Nitrate,"A convenient approach for the synthesis of tetrasubstituted pyrazoles is described. The method involves the treatment of 1,3-diketones and allyltrimethylsilane with CAN followed by cerium-catalyzed addition of substituted hydrazines to construct pyrazoles in good yields.",10.1055/s-0029-1217163,2009-05-13,0.5986553570289279
Synthesis,First Construction of a Saricandin Analog Corresponding to Papulacandin D,"The first total synthesis of a saricandin analog corresponding to papulacandin D has been achieved via a highly convergent synthetic strategy. A readily accessible chiral building block 3 was designed and prepared in large scale via an enantioselective reduction with pinanyl-9-BBN. The adaptability of compound 3 toward structural modifications and the highly convergent nature of the approach is illustrated in the construction of the side chain present in saricandin by Pd-catalyzed cross-coupling of 2 and 3 and sequences that include triple bond reduction of fragment C(5-16) and generation of the double bond (C4-C5) using Horner-Emmons reaction. The assembly of the spirocyclic monoglycoside with saricandin side chain is described. A practical technique for isolating the final product 1 after deprotection with TBAF is discussed. Compound 1 was evaluated for its antifungal activity in enzyme assay and cell based assays. However, in contrast the activity reported by Traxler for papulacandin D, the presence of the galactose moiety together with the short fatty acid in natural saricandin seem to be essential for the antifungal activity.",10.1055/s-2001-13399,2001-01-01,0.5986543353172815
Organic Process Research & Development,"Practical Synthesis of Low-Density Lipoprotein Receptor Upregulator, <i>N</i>-[1-(3-Phenylpropane-1-yl)piperidin-4-yl]-5-thia-1,8<i>b</i>-diazaacenaphthylene-4- carboxamide","A shorter and more practical method for the preparation of N -[1-(3-phenylpropane-1-yl)piperidin-4-yl]-5-thia-1,8 b -diazaacenaphthylene-4-carboxamide ( 4 ) as an upregulator of the LDL receptor has been developed. 1-(3-Phenylpropyl)piperidin-4-amine ( 7 ) was synthesized with 71% yield by the alkylation of 4-aminopyridine ( 5 ) with 3-phenylpropylbromide followed by reduction with NaBH 4 in the presence of base in a mixture of 2-propanol and methanol. The addition of base (1 equiv), for example, KOH and NaOMe, in the above reduction afforded a decrease of 1-(3-phenylpropyl)- N -[1-(3-phenylpropyl)piperidin-4-yl]piperidin-4-amine ( 8 ) to increase the yield of 7 . The amidation of 5-thia-1,8 b -diazaacenaphthylene-4-carboxylic acid ( 1 ) with the primary amine ( 7 ) using EDCI in the presence of HOBt (0.2 equiv) provided 4 in 94% yield.",10.1021/op0101106,2002-03-22,0.5986493913292232
Organic Process Research & Development,Regioselective Functionalization of 4-Methyl-1<i>H</i>-indole for Scalable Synthesis of 2-Cyano-5-formyl-4-methyl-1<i>H</i>-indole,"We report a five-step synthesis of 2-cyano-5-formyl-4-methyl-1 H -indole through sequential functionalization of readily available 4-methyl-1 H -indole. Cyano and aldehyde functionalities are regioselectively installed at the 2 and 5 position, respectively. The sequence is concise and high-yielding, amenable for kilogram scale production.",10.1021/acs.oprd.7b00370,2017-12-27,0.5986487262741633
European Journal of Organic Chemistry,"Synthesis of a Key Building Block for a Butyrolactone → 1,3-Diol Approach to the Polyol Part of Roflamycoin","For preparing tris(γ-lactone) 3 the mono(γ-lactone) 6 was synthesized from the dichlorodiol 12 (99.8% ee). Bisepoxide 9 – derived from dichlorodiol 12 (99.8% ee) – was ring-opened with the Gilman cuprate from 2-lithio-1,5-hexadiene and CuI giving almost exclusively the monoepoxide 21; in five more steps, γ-lactone 30 with the same stereotriad as the target molecule 6 but a different protecting group was obtained. Monoepoxide 33 – also derived from dichlorodiol 12 – was ring-opened with the same Gilman cuprate affording compound 35. It was transformed into the correctly protected γ-lactone 6 in seven steps, key reactions being the ozonolysis 35 → 36 and the diastereoselective reduction 36 → anti-37.",10.1002/(sici)1099-0690(199806)1998:6<1031::aid-ejoc1031>3.3.co;2-4,1998-06-01,0.598644060311854
European Journal of Organic Chemistry,"Synthesis of a Key Building Block for a Butyrolactone → 1,3-Diol Approach to the Polyol Part of Roflamycoin","For preparing tris(γ-lactone) 3 the mono(γ-lactone) 6 was synthesized from the dichlorodiol 12 (99.8% ee). Bisepoxide 9 – derived from dichlorodiol 12 (99.8% ee) – was ring-opened with the Gilman cuprate from 2-lithio-1,5-hexadiene and CuI giving almost exclusively the monoepoxide 21; in five more steps, γ-lactone 30 with the same stereotriad as the target molecule 6 but a different protecting group was obtained. Monoepoxide 33 – also derived from dichlorodiol 12 – was ring-opened with the same Gilman cuprate affording compound 35. It was transformed into the correctly protected γ-lactone 6 in seven steps, key reactions being the ozonolysis 35 → 36 and the diastereoselective reduction 36 → anti-37.",10.1002/(sici)1099-0690(199806)1998:6<1031::aid-ejoc1031>3.0.co;2-d,1998-06-01,0.598644060311854
Angewandte Chemie International Edition,Total Synthesis of Isodaphlongamine H: A Possible Biogenetic Conundrum,"Herein we describe the first synthetic efforts toward the total synthesis of isodaphlongamine H, a calyciphylline B-type alkaloid. The strategy employs a chemoenzymatic process for the preparation of a functionalized cyclopentanol with a quaternary center. This molecule is elaborated to form an enantiopure 1-aza-perhydrocyclopentalene core, representing rings A and E of all calyciphylline B-type alkaloids. Further transformations involve the formation of a cyclic enaminone, 1,4-conjugate addition with a cyclopentenyl subunit, and intramolecular aldol cyclization to achieve a pentacyclic intermediate, ultimately forming isodaphlongamine H in a total of 24 steps from the commercially available compound 2-carbethoxycyclopentanone. Isodaphlongamine H exhibits promising inhibitory activity against a panel of human cancer cell lines.",10.1002/anie.201510861,2016-01-14,0.5986341717692685
Tetrahedron,Synthesis and chemiluminescent properties of the peroxy acid compound as an intermediate of coelenterate luciferin luminescence,,10.1016/s0040-4039(97)00430-9,1997-04-01,0.5986335306504297
Angewandte Chemie International Edition,"A Route to the Thapsigargins from (<i>S</i>)‐Carvone Providing a Substrate‐Controlled Total Synthesis of Trilobolide, Nortrilobolide, and Thapsivillosin F","An entirely substrate-controlled total synthesis of three members of the thapsigargin family (e.g. trilobolide) is achieved starting from (S)-carvone. The synthesis is linear in nature but is achieved in high yield (>90 % per step). The route permits late-stage divergence, providing access to a range of natural products and structural analogues.",10.1002/anie.200353140,2003-12-10,0.5986293038917517
Tetrahedron,Synthesis of glutamate agonists and anatagonists by a ring switching strategy,,10.1016/0040-4039(95)01517-5,1995-10-01,0.5986230370308265
Journal of Organic Chemistry,An Olefin Cross-Metathesis Approach to Depudecin and Stereoisomeric Analogues,"A new total synthesis of the natural product (-)-depudecin, a unique and unexplored histone deacetylase (HDAC) inhibitor, is reported. A key feature of the synthesis is the utilization of an olefin cross-metathesis strategy, which provides for an efficient and improved access to natural depudecin, compared with our previous linear synthesis. Featured by its brevity and convergency, our developed synthetic strategy was applied to the preparation of the 10-epi derivative and the enantiomer of depudecin, which represent interesting stereoisomeric analogues for structure-activity relationship studies.",10.1021/acs.joc.7b00424,2017-04-11,0.5986209763927722
Journal of Organic Chemistry,Enantioselective Synthesis of (<i>R</i>)-Bufuralol via Dynamic Kinetic Resolution in the Key Step,An enantioselective synthesis of (R)-bufuralol via a ruthenium- and enzyme-catalyzed dynamic kinetic resolution (DKR) has been achieved. The synthesis starts from readily available 2-ethylphenol and provides (R)-bufuralol in high ee and a good overall yield of 31%.,10.1021/jo100936f,2010-06-04,0.598620167536857
Tetrahedron,Studies in marine macrolide synthesis: Synthesis of a C16C28 subunit of spongistatin 1 (altohyrtin A) incorporating the CD-spiroacetal moiety,,10.1016/s0040-4039(97)10483-x,1997-12-01,0.5986019149703777
Synthesis,Simple and Efficient Asymmetric Synthesis of Furofuran Lignans Yangambin and Caruilignan A,"A novel asymmetric dimerization of cinnamic acid derivative was achieved in high efficiency and high stereoselectivity. By using the reaction as a key step, two furofuran lignans, yangambin and caruilignan A were synthesized in optically pure form in only 5 and 6 steps, respectively.",10.1055/s-2006-926271,2006-01-01,0.598595641076253
Organic Letters,Total Synthesis of (−)-FD-838 and (−)-Cephalimysin A,We completed a nine-step total synthesis of (-)-FD-838 and (-)-cephalimysin A. Our synthesis features a biogenetically guided assembly of the highly oxidized spirocyclic core by Snider-type tandem epoxidations of the chiral substrate derived from an amino acid derivative. Our synthetic approach provides a general and versatile solution to access spirocyclic PKS-NRPS-based secondary fungal metabolites.,10.1021/acs.orglett.9b02203,2019-07-22,0.5985931329763909
Tetrahedron,"Utilization of the chiral synthon, methyl 3-O-benzyl-2,4,6-trideoxy-6-iodo-α-D--hexopyranoside in the synthesis of a potent HMG-CoA reductase inhibitor",,10.1016/s0040-4039(00)98588-5,1985-01-01,0.5985924647928484
Organic Letters,An Enantioselective Entry to <i>cis</i>-Perhydroisoquinolines,"An enantioselective route to cis-perhydroisoquinolines, involving a cyclocondensation reaction of (R)-phenylglycinol with a racemic oxoester, a stereoselective conjugate addition to an unsaturated bicyclic lactam, and the closure of the carbocyclic ring by a ring-closing metathesis as the key steps is reported. This route allows the preparation of 3-cyano derivatives as well as cis-octahydroisoquinolines bearing a quaternary center at the C4-position. [reaction: see text]",10.1021/ol051242c,2005-07-27,0.5985920805129501
Tetrahedron,Synthesis of a rhazinilam analogue acting as an inhibitor of tubulin assembly,,10.1016/s0040-4039(00)00983-7,2000-07-01,0.5985849961320391
Tetrahedron,"A two-step, one-pot route to swap the pyrroline moiety in meso-tetraaryldihydroxy-chlorins with an O/N-substituted oxazoline",,10.1016/j.tetlet.2013.01.070,2013-01-31,0.5985715663477568
Journal of the American Chemical Society,Total Synthesis of Pentacyclic (−)-Ambiguine P Using Sequential Indole Functionalizations,"The first synthesis of a pentacyclic ambiguine (ambiguine P) is reported. The synthesis takes advantage of sequential alkylations of an indole core to rapidly construct the pentacyclic framework of the natural product. Key to the success of the synthesis was the use of a Nicholas reaction to alkylate at C2, crafting a fused seven-membered ring that is characteristic of the pentacyclic ambiguines, as well as the use of an amide-directed functionalization at C12 to set a requisite quaternary center. A versatile late-stage intermediate was prepared that may be applicable to the synthesis of the other pentacyclic ambiguines.",10.1021/jacs.8b13388,2019-01-31,0.5985595302200344
Journal of the American Chemical Society,Enantioselective Total Synthesis of Aplyviolene,The enantioselective total synthesis of the rearranged spongian diterpene aplyviolene has been completed in 14 steps from the known hydroazulenone 8. The key junction of the hydrocarbon and oxygenated fragments to form the critical C8 quaternary carbon stereocenter and set the stage for elaborating the delicate bicyclic lactone functionality was accomplished in high yield and exquisite stereoselectivity by Michael addition of an enantioenriched hydroazulenone enolate to an enantiopure α-bromocyclopentenone.,10.1021/ja208018s,2011-09-23,0.5985565032914342
Journal of Organic Chemistry,Synthesis of the HCV Protease Inhibitor Vaniprevir (MK-7009) Using Ring-Closing Metathesis Strategy,A highly efficient synthesis of Vaniprevir (MK-7009) has been accomplished in nine linear steps and 55% overall yield. The key features of this synthesis include a cost-effective synthesis of the isoindoline subunit and efficient construction of the 20-membered macrocyclic core of Vaniprevir (MK-7009) utilizing ring-closing metathesis technology. A high-performing ring-closing metathesis protocol has been achieved by simultaneous slow addition of the ruthenium catalyst (0.2 mol %) and the diene substrate at a concentration of 0.13 M.,10.1021/jo3001595,2012-03-29,0.598535331605874
Synlett,An Improved Method for the Preparation of Protected (R)-2-Methylcysteine: Solution-Phase Synthesis of a Glutathione Analogue,A synthetic method for the preparation of (R)-2-methylcysteine that dramatically improves the overall yield of this important unnatural amino acid has been refined. The key steps in the preparation of (R)-2-methylcysteine were improved such that necessary intermediates were prepared in high yields and of sufficient purity to avoid the need for distillation or column chromatography. The ( R)-2-methylcysteine was prepared (&gt; 90% ee) in appropriately protected form and used in a novel solution phase synthesis of a glutathione analogue.,10.1055/s-0030-1259021,2010-11-03,0.5985331793952777
Journal of Organic Chemistry,CuCN-Mediated Cascade Cyclization of 4-(2-Bromophenyl)-2-butenoates: A High-Yield Synthesis of Substituted Naphthalene Amino Esters,"A new method of CuCN-mediated one-pot cyclization of 4-(2-bromophenyl)-2-butenoates leading to efficient synthesis of substituted naphthalene amino esters including phenanthrene aromatic structural units is described. Deuterium labeling studies establish that this one-pot cascade cyclization proceeds through isomerization of olefin, intramolecular C-C bond cyclization, and aromatization as the key intermediates, all occurring in a single step.",10.1021/jo400244h,2013-04-17,0.5985303756242001
Organic Process Research & Development,Hydroformylation and Late-Stage Diversification on Densely Functionalized Cores of Influenza Endonuclease Inhibitors,"This work describes synthetic strategies to access diverse chemical matter in a series of inhibitors of the cap-dependent Flu endonuclease. Our approaches toward this goal encompass (i) the development of a modular, diastereoselective route to the tricyclic cores and (ii) the use of advanced intermediates for late-stage diversification. Key to realizing both strategies is the development of an efficient, functional group-tolerant, chemoselective hydroformylation step that can be executed in the presence of the metal binding motif common to this inhibitor family. The established synthetic route provides access to advanced intermediates on gram scale. Furthermore, late-stage diversification conditions that tolerate the presence of the pyridone-based binding motif are reported, allowing for rapid access to a broad range of chemical matter.",10.1021/acs.oprd.4c00277,2024-08-16,0.5985303447289192
Journal of the American Chemical Society,Total Synthesis of Bryostatin 7 <i>via</i> C–C Bond-Forming Hydrogenation,"The marine macrolide bryostatin 7 is prepared in 20 steps (longest linear sequence) and 36 total steps with five C-C bonds formed using hydrogenative methods. This approach represents the most concise synthesis of any bryostatin reported, to date.",10.1021/ja205673e,2011-07-22,0.5985282910866688
Tetrahedron,"A novel synthetic route to ethyl 3-substituted-trans-2,3-difluoro-2-acrylates and their reactions with nucleophiles",,10.1016/s0040-4039(00)01517-3,2000-10-01,0.5985241872857376
European Journal of Organic Chemistry,Synthesis of Spirolactones from the Limonene System,"Four enantiomeric pairs of spirolactones were obtained in a four step synthesis from (+) and (−) limonene. The Claisen rearrangement and iodolactonization were the key steps of the syntheses presented. The structures of products were confirmed by X-ray crystallography of 11, 18b, and 19.",10.1002/(sici)1099-0690(199811)1998:11<2677::aid-ejoc2677>3.0.co;2-p,1998-11-01,0.5985131712258394
Synthesis,Recent Advances in the Total Synthesis of Cephalotane-Type Norditerpenoids from Cephalotaxus sinensis,"Abstract Cephalotaxus diterpenoids are well known for their unique structures and biological activities. Cephanolides, as new cephalotane-type norditerpenoids isolated from Cephalotaxus sinensis, have attracted considerable attention from the synthetic community. The present Short Review summarizes strategic approaches toward the total synthesis of cephanolides from 2018 to 2021. 1 Introduction 2 Synthetic Approaches toward Cephalotane-Type Norditerpenoids 2.1 First Total Synthesis of Cephanolides B and C by Zhao (2018) 2.2 Total Synthesis of Cephanolides A–D by Sarpong (2021) 2.3 Total Synthesis of Cephanolide B by Yang (2021) 2.4 Asymmetric Total Synthesis of Cephanolide A by Gao (2020) 2.5 Asymmetric Total Synthesis of Cephanolide B by Gao (2021) 2.6 Asymmetric Total Synthesis of Cephanolides A and B by Cai (2021) 3 Conclusion and Perspectives",10.1055/a-1828-2170,2022-04-19,0.5985120968017889
Tetrahedron,Palladium-catalyzed ring expansion reaction of 1-alkynylcyclobutanols with aryl iodides: an efficient route to 2-disubstituted methylenecyclopentanones,,10.1016/s0040-4039(02)02581-9,2003-01-01,0.5985108363868521
Synlett,Synthesis of 2-Quinolinones through Palladium(II) Acetate Catalyzed Cyclization of N-(2-Formylaryl)alkynamides,A Pd(OAc) 2 -catalyzed cyclization of N -(2-formyl­aryl)alkynamides initiated by the oxypalladation of alkynes was developed. The method provides a new approach for the efficient and atom-economical synthesis of 2-quinolinone derivatives.,10.1055/s-0034-1380751,2015-06-01,0.5985013948854954
Tetrahedron,L-Ribulose: A novel chiral pool compound,,10.1016/0040-4039(90)80222-8,1990-01-01,0.5984919945080666
Organic Process Research & Development,Development of a Green and Sustainable Manufacturing Process for a Key Intermediate to Nemtabrutinib (MK-1026): Sequential Deprotonation–Lithiation as a Batch–Flow Process,"Nemtabrutinib (MK-1026) is a novel oral Bruton’s tyrosine kinase (BTK) inhibitor for treatment of B-cell cancers. An initial synthetic supply route to generate ketone 3 relied on the generation of a highly reactive transient intermediate and the use of n -butyllithium. Cryogenic temperatures (−60 °C) were also required to achieve a modest 61% yield, with one major impurity, resulting from dehalogenation, accounting for the majority of the mass balance. An alternative process was developed to increase the yield and decrease the dependence on cryogenic temperatures, and this advancement was critical to the long-term robustness of the commercial process. Key advancements included performing the requisite deprotonation and metalation steps sequentially and performing the metalation and quench steps in flow. The final flow process was rapidly scaled from grams to tens of kilograms and has been successfully executed in a production facility.",10.1021/acs.oprd.3c00510,2024-05-09,0.5984868592052691
Green Chemistry,"An environmentally benign and efficient synthesis of substituted benzothiazole-2-thiols, benzoxazole-2-thiols, and benzimidazoline-2-thiones in water","An efficient and practical method for the one-step synthesis of benzothiazole-2-thiols, benzoxazole-2-thiols and benzimidazoline-2-thiones in water was described.",10.1039/c7gc02311a,2017-01-01,0.5984844771148494
Journal of Organic Chemistry,Synthesis of BF<sub>2</sub> Complexes of Prodigiosin Type Oligopyrroles,"We developed a simple, facile route for the synthesis of BF(2) complexes of prodigiosin type oligopyrroles and their cholesterol conjugates. This route gives an access to synthesize any desired meso-aryl-substituted 3-pyrrolyl BODIPYs which were not easily accessible earlier.",10.1021/jo201183s,2011-07-29,0.598482607047667
Organic Letters,Synthesis of the Carboline Disaccharide Domain of Shishijimicin A,"A synthetic route to the carboline disaccharide domain (2) of shishijimicin A (1) has been developed. The convergent synthesis relies on a novel application of the Reetz-Müller-Starke reaction to form the central, sulfur-bearing quaternary carbon center and addition of the carboline structural motif as a dianion to a disaccharide aldehyde fragment.",10.1021/ol201444t,2011-06-28,0.5984798735088178
Organic Process Research & Development,Building a Quaternary Stereogenic Center on Dihydroazaindole Carboxylic Acid through Scalable Process Development,"Due to their unique properties, dihydroazaindoles are important fragments of active pharmaceutical ingredients and are of great interest in the pharmaceutical industry. In this manuscript, a scalable and economical process for the synthesis of a complex ( R )-2-(4-fluorophenyl)-2-methyl-2,3-dihydro-1 H -pyrrolo[2,3- b ]pyridine-5-carboxylic acid ( R )-1 on multikilogram scale is described. The synthesis was advanced through a second-generation synthetic strategy that did not rely on chiral Supercritical Fluid Chromatography separation, which was the highest cost driver. Through systematic screening of chemical resolution, we found that compound ( R )-1 can be isolated with high (>99%) enantiomeric excess. Furthermore, the mother liquor from the first resolution process was recyclable to racemize the S -isomer into ( R )-1 and ( S ) - 1 mixtures, which could be used for an additional chemical resolution process. The precious palladium (Pd) complexes could be reduced from 20 mol % to 1 mol %, and the long lead time building blocks were safely prepared in-house. Advanced intermediates were efficiently synthesized by reducing isolation steps through one-pot process development. The regulatory starting material compound ( R )-1·HCl was isolated with a high purity profile after di- p -toluoyl- d -tartaric acid salt breaking and HCl salt formation.",10.1021/acs.oprd.3c00231,2023-10-09,0.5984714933613857
Journal of Organic Chemistry,Total Synthesis of (+)-Zaragozic Acid C,"A total synthesis of (+)-zaragozic acid C is described. Key features of the synthesis are the use of a double Sharpless asymmetric dihydroxylation reaction of diene 6 to control stereochemistry at four contiguous stereocenters from C3 to C6; the introduction of the C1-side chain by reaction between the anion derived from the dithiane monosulfoxide 27 and the core aldehyde 12; a high yielding, acid-mediated simultaneous acetonide deprotection−dithiane removal−ketalization procedure leading exclusively to the 2,8-dioxabicyclo[3.2.1]octane core 34; and a novel triple oxidation procedure allowing installation of the tricarboxylic acid.",10.1021/jo000700m,2000-09-16,0.5984692459083669
Journal of Organic Chemistry,Synthetic studies toward verrucarol. 2. Synthesis of the AB ring system,A route to the AB ring system of verrucarol is described. The successful scheme involved the formation of the A ring by a boron triacetate catalyzed Diels-Alder reaction. The second ring can be appended by an intramolecular Knoevenagel reaction to afford lactone 12b. This lactone could be converted into the desired keto alcohol 3b by reduction of the lactone and nitrile followed by an oxidation and Curtius degradation.,10.1021/jo01312a004,1980-11-01,0.5984669347862155
Tetrahedron,"Facile reduction of malonate derivatives using NaBH4/Br2: an efficient route to 1,3-diols",,10.1016/j.tetlet.2007.12.001,2007-12-05,0.5984642958223119
Angewandte Chemie International Edition,Frontispiece: Catalytic Asymmetric Synthesis of the anti‐COVID‐19 Drug Remdesivir,Asymmetric Synthesis The first catalytic asymmetric synthesis of remdesivir by the coupling of the P-racemic phosphoryl chloride with protected nucleoside GS441524 is described by W. Zhang et al. in their Communication on page 20814.,10.1002/anie.202084761,2020-11-09,0.5984604099883996
Organic Letters,Enantioselective Synthesis of α-Methylene-β-hydroxy Carboxylic Acid Derivatives via a Diastereoselective Aldol/β-Elimination Sequence: Application to the C(15)−C(21) Fragment of Tedanolide C,"An enantioselective synthesis of alpha-methylene-beta-hydroxy carboxylic acid derivatives via a highly diastereoselective, one-pot syn-aldol and beta-elimination sequence utilizing the chiral beta-(phenylselenyl)propionyl imide 15 is described. This new method, which constitutes an alternative to the Baylis-Hillman reaction, has been applied to the synthesis of the C(15)-C(21) fragment of tedanolide C.",10.1021/ol1006955,2010-04-20,0.598454347541702
Journal of Organic Chemistry,Asymmetric Total Synthesis of Chaetoglobin A,"An asymmetric total synthesis of chaetoglobin A was achieved. Atroposelective oxidative coupling of a phenol incorporating all but one carbon of the final product was used as a key step to generate axial chirality. The stereochemical outcome of the catalytic oxidative phenolic with the highly substituted phenol used herein was found to be opposite that of the simpler congeners reported previously, providing a cautionary tale about extrapolating asymmetric processes from simple to more complex substrates. Optimization of the postphenolic coupling steps including formylation, oxidative dearomatization, and selective deprotection steps are outlined. The tertiary acetates of chaetoglobin A were exceptionally labile due to activation by the adjacent keto groups, which complicated each of these steps. In contrast, the final oxygen to nitrogen exchange proceeded readily and the spectroscopic data from the synthetic material matches that of the isolated natural product in all respects.",10.1021/acs.joc.3c00002,2023-05-17,0.5984529241355808
Organic Letters,Total Synthesis of Russuphelol: A Case of Mistaken Chirality,"The chlorohydroquinone tetramer, russuphelol, does not have stereocenters; however, it was reported as a chiral optically active substance with stable enantiomeric conformations. The natural product is synthesized in six steps and 14% overall yield. Synthetic material was used to experimentally investigate its chiral properties.",10.1021/ol502459p,2014-09-10,0.5984505885080477
Tetrahedron,Improved conditions for the Kiliani-Fischer synthesis,,10.1016/0040-4039(96)01270-1,1996-08-01,0.5984503439387017
Journal of the American Chemical Society,Azoles as Auxiliaries and Intermediates in Prebiotic Nucleoside Synthesis,"High Resolution Image Download MS PowerPoint Slide 4,5-Dicyanoimidazole and 2-aminothiazole are azoles that have previously been implicated in prebiotic nucleotide synthesis. The former compound is a byproduct of adenine synthesis, and the latter compound has been shown to be capable of separating C 2 and C 3 sugars via crystallization as their aminals. We now report that the elusive intermediate cyanoacetylene can be captured by 4,5-dicyanoimidazole and accumulated as the crystalline compound N- cyanovinyl-4,5-dicyanoimidazole, thus providing a solution to the problem of concentration of atmospherically formed cyanoacetylene. Importantly, this intermediate is a competent cyanoacetylene surrogate, reacting with ribo- aminooxazoline in formamide to give ribo- anhydrocytidine ─ an intermediate in the divergent synthesis of purine and pyrimidine nucleotides. We also report a prebiotically plausible synthesis of 2-aminothiazole and examine the mechanism of its formation. The utilization of each of these azoles enhances the prebiotic synthesis of ribonucleotides, while their syntheses comport with the cyanosulfidic scenario we have previously described.",10.1021/jacs.2c07774,2022-10-17,0.5984493894247395
Journal of the American Chemical Society,Immunoproteasome Inhibitor–Doxorubicin Conjugates Target Multiple Myeloma Cells and Release Doxorubicin upon Low-Dose Photon Irradiation,"Proteasome inhibitors are established therapeutic agents for the treatment of hematological cancers, as are anthracyclines such as doxorubicin. We here present a new drug targeting approach that combines both drug classes into a single molecule. Doxorubicin was conjugated to an immunoproteasome-selective inhibitor via light-cleavable linkers, yielding peptide epoxyketone-doxorubicin prodrugs that remained selective and active toward immunoproteasomes. Upon cellular uptake and immunoproteasome inhibition, doxorubicin is released from the immunoproteasome inhibitor through photoirradiation. Multiple myeloma cells in this way take a double hit: immunoproteasome inhibition and doxorubicin-induced toxicity. Our strategy, which entails targeting of a cytotoxic agent, through a covalent enzyme inhibitor that is detrimental to tumor tissue in its own right, may find use in the search for improved anticancer drugs.",10.1021/jacs.9b11969,2020-04-10,0.5984349498362915
Organic Process Research & Development,Development of a Synthesis For a Long-Term Oxazolidinone Antibacterial,"Linezolid, compound 1, is a member of the oxazolidinone class of antibacterials and has had recent clinical interest due to its potential use as a long-term treatment for bacterial infection. Detailed herein are improvements to the original synthesis to enable phase I clinical trials. Of particular interest is the preparation of a key oxindole subunit utilizing a Pd-mediated cyclization. Optimization of the synthesis of the oxindole included the use of trifluorotoluene as the solvent.",10.1021/op8001195,2008-08-16,0.5984252975934943
Tetrahedron,Synthesis of 7α-substituted cephalosporins Part IV. Novel synthesis of 7α-methylcephalosporins,,10.1016/s0040-4039(00)93791-2,1976-05-01,0.5984218356614984
Tetrahedron,"Regioselective reduction of 2,3-epoxy alcohol derivatives. An efficient route to enantiomerically pure 2-alkanols",,10.1016/s0040-4039(00)77666-0,1992-01-01,0.5984001952859367
Organic Letters,"Total Synthesis of Oidiodendrolides and Related Norditerpene Dilactones from a Common Precursor: Metabolites CJ-14,445, LL-Z1271γ, Oidiolactones A, B, C, and D, and Nagilactone F","An efficient, high-yielding strategy has been developed for the asymmetric total synthesis of seven norditerpenoid dilactones known for their diverse biological properties. The three key steps employed to obtain a tricyclic lactone intermediate involved a Morita-Baylis-Hillman reaction, the stereocontrolled construction of a gamma-lactone through bromolactonization, and an efficient catalytic Reformatsky-type reaction. Access to CJ-14,445, LL-Z1271gamma, oidiolactones A, B, C, and D, and nagilactone F was possible from a common intermediate. Structures and stereochemistry were determined by X-ray analysis.",10.1021/ol901896c,2009-09-24,0.5983940945553561
Organic Letters,Synthesis of Methyl-Protected (±)-Chlorizidine A,"The first total synthesis of the methyl-protected (±)-chlorizidine A has been achieved in 10 steps. Pd-catalyzed decarboxylative coupling and late-stage oxidation were utilized to construct the 5H-pyrrolo[2,1-a]isoindol-5-one scaffold. Samarium(II) iodide mediated Reformatsky reaction and intramolecular Mitsunobu reactions were efficiently applied for the synthesis of the 2,3-dihydropyrrolizine ring system. Chlorizidine A is highly prone to degradation; hence, methyl-protected (±)-chlorizidine A was prepared.",10.1021/acs.orglett.7b01090,2017-05-03,0.5983920030889094
Synthesis,"Polycyclic<i>N</i>-Hetero Compounds. XLII: Convenient Syntheses of 6, 7-Dihydro-5<i>H</i>-pyrido[2,3-<i>b</i>]pyrimido[4,5-<i>d</i>]azepine as a Novel Polyheterocyclic Ring System and Its 4-Substituted Derivatives","All articles of this category A convenient synthetic route for the syntheses of 6,7-dihydro-5 H -pyrido[2, 3- b ]pyrimido[4,5- d ]azepine and its 4-substituted derivatives starting from ethyl 2-aminopyridine-3-carboxylate is described as the fist example of the unknown ring system. A new class of anti-platelet aggregation activity for them against collagene-induced aggregation of rabbit blood platelet in vitro was found.",10.1055/s-1991-26613,1991-01-01,0.5983799853867552
Tetrahedron,A novel route to stable silacyclopropenes - First synthesis of silacyclopropenes bearing vinylic hydrogen,,10.1016/0040-4039(93)88099-5,1993-10-01,0.5983718208188739
Tetrahedron,"An efficient synthesis of protected (2R,3R,4S)-4,7-diamino-2,3-dihydroxyheptanoic acid, a constituent of callipeltins A and D",,10.1016/s0040-4039(03)01368-6,2003-07-01,0.5983572986777344
Journal of the American Chemical Society,Dysinosin A:  A Novel Inhibitor of Factor VIIa and Thrombin from a New Genus and Species of Australian Sponge of the Family Dysideidae,"A new marine natural product dysinosin A 1 has been isolated from a new genus and species of sponge of the family Dysideidae found near Lizard Island, North Queensland, Australia. Dysinosin A is a potent inhibitor of the blood coagulation cascade factor VIIa and an inhibitor of the serine protease thrombin. Among the distinctive features of dysinosin A are the presence of a 5,6-dihydroxy-octahydroindole-2-carboxylic acid, 3-amino-ethyl 1-N-amidino-Delta-3-pyrroline, a sulfated glyceric acid, and d-leucine, assembled through three peptidic linkages. Dysinosin A inhibited factor VIIa at a Ki of 108 nM and thrombin at a Ki of 452 nM. The identification of the 1-N-amidino-Delta-3-pyrroline and 5,6-dihydroxy-octahydroindole-2-carboxylic acid as P1 and P2 moieties respectively, should pave the way for the design and synthesis of new structure-based inhibitors.",10.1021/ja020814a,2002-10-17,0.5983572231478684
Journal of Organic Chemistry,Stereoselective Total Synthesis of Racemic BCX-1812 (RWJ-270201) for the Development of Neuraminidase Inhibitors as Anti-influenza Agents,"A convergent and versatile racemic total synthesis of the anti-influenza agent BCX-1812 (RWJ-270201) was accomplished on the basis of a sequence of stereoselective reactions. Despite intensive research to develop neuraminidase inhibitors to treat infections due to influenza, currently available agents are still in the need of optimization with respect to selectivity and potency, as well as to minimize adverse effects. Our synthetic approach, introduced in this report, is highly exploitable for further derivatization due to flexibility that will eventually accommodate diversified substituents. In addition, the size of the core ring can be varied depending on the size of the diene used for the preparation of the key cycloadduct 10 using an acylnitroso-based hetero-Diels-Alder reaction. Elaboration of 10 to methyl ester 14 followed by a precedented [3+2] dipolar cycloaddition gave bicyclic isoxazoline 17 in a regio- and stereoselective fashion. Incorporation of the peripheral guanidino group and subsequent deprotection provided the target molecule. The details of the synthesis are described herein.",10.1021/jo034316b,2003-07-29,0.5983570372476881
Tetrahedron,A facile synthetic route to (±)-chrysanthemate analogues,,10.1016/0040-4039(76)80115-3,1976-11-01,0.5983555415445858
Journal of Organic Chemistry,Synthesis of Fluoroalkylated β-Aminophosphonates and Pyridines from Primary β-Enaminophosphonates,A simple and efficient stereoselective synthesis of fluorine containing beta-aminophosphonates by reduction of beta-enaminophosphonates is described. Reduction with sodium cyanborohydride in the presence of zinc chloride and the catalytic hydrogenation of beta-enaminophosphonates gives beta-aminophosphonates. beta-Enaminophosphonates are also used as intermediates for the regioselective synthesis of fluoroalkyl-substituted pyridines.,10.1021/jo8005667,2008-05-20,0.5983535787558492
European Journal of Organic Chemistry,The Application of [γ‐(Silyloxy)allylidene]ditin to the Efficient Synthesis of the Chromophore of the Neocarzinostatin Dihydroxycyclopentene‐Based Dienediyne Core,"Abstract 1‐( tert ‐Butyldimethylsilyl)oxy‐3,3‐bis(tributylstannyl)propene ( 5 ), a versatile gem ‐dimetallic allylic synthon accessible through various synthetic routes, has been condensed with (trimethylsilyl)propiolaldehyde to give the fully functionalised acyclic vinyltin compound 9h , which is a precursor of the complex dihydroxycyclopentene sub‐unit of neocarzinostatin chromophore (NCS) 1 . Subsequent transformation into the geminal ( E )‐α‐chloro‐( Z )‐α‐iodovinylic intermediate 20 , followed by a palladium‐catalysed carbometallation/cyclisation reaction including in situ trapping with either (tributylstannyl)acetylene or the more functionalised 3,3‐diethoxy‐1‐(tributylstannyl)prop‐1‐yne delivered the corresponding alkyne‐substituted 4‐chloro‐1,2‐bis(silyloxy)cyclopent‐3‐enes 21 or 22 , respectively. Chlorocyclopentene 21 was subsequently easily transformed into the target dienediyne adduct 23 by Sonogashira condensation with trimethylsilylacetylene. This diastereoselective process is efficient with only six steps and an overall 26 % yield from the allylic ditin precursor 5 . More than just an NCS building block, the final acyclic dihydroxycyclopentene‐based dienediyne is also a seco analogue of the NCS chromophore. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2006)",10.1002/ejoc.200500353,2005-11-16,0.5983533374668929
Tetrahedron,Efficient synthesis of 4-O- and C-substituted-7-azaindoles,,10.1016/j.tetlet.2006.01.143,2006-02-20,0.5983526258952795
Tetrahedron,An efficient synthesis of substituted chrysenes,,10.1016/j.tetlet.2016.12.004,2016-12-09,0.5983526258952795
Tetrahedron,An efficient synthesis of substituted anthraquinones and naphthoquinones,,10.1016/j.tetlet.2004.02.010,2004-03-01,0.5983526258952795
Synthesis,"An Efficient Synthesis of 2-Substituted 1,3-Thiazoles",,10.1055/s-1974-23301,1974-01-01,0.5983526258952795
Tetrahedron,Efficient and connective synthesis of substituted butyrolactones and exo-methylene butyrolactones,,10.1016/s0040-4039(00)01840-2,2000-12-01,0.5983526258952795
Tetrahedron,An efficient synthesis of substituted prolines by the selective reduction and reductive cyanation of 2-pyrrolidones,,10.1016/s0040-4039(02)00097-7,2002-02-01,0.5983458056682308
Synthesis,Organocatalytic Enantioselective Approach to the Synthesis of Verbalactone and (R)-Massoialactone,The organocatalytic enantioselective synthesis of verbalactone and (R)-massoialactone is described. The requisite stereogenic centers of the target molecules were constructed using l-proline-catalyzed α-aminoxylation and Horner-Wadsworth-Emmons­ (HWE) olefination. Yamaguchi macrolactonization and ring-closing metathesis were employed as key steps in the syntheses.,10.1055/s-0030-1260051,2011-05-17,0.5983457138849642
Synthesis,Total Synthesis of (±)-Kelsoene,(±)-Kelsoene (1) has been synthesized in 15 steps from commercially available cyclopent-2-en-1-one. Key steps include (a) a methylenecyclopentane annulation of cyclopent-2-en-1-one using the bifunctional cuprate reagent lithium cyano(4-chlorobut-1-en-2-yl)cuprate and (b) a highly stereoselective [2+2]-photocycloaddition of ethylene to the bicyclic enone 10.,10.1055/s-2001-18063,2001-01-01,0.5983429231998743
Journal of Organic Chemistry,Total Synthesis of (−)-Isoavenaciolide,"An enantioselective approach to (-)-isoavenaciolide was achieved starting from 1-undecyn-3-ol. The synthesis relied upon the preparation of a chiral 4-silyloxy-2-alkenylborane by hydroboration of a protected 2,3-allenol and subsequent stereoselective addition to 2-thiophenecarboxaldehyde.",10.1021/jo302598h,2013-01-21,0.5983357327895358
Organic Letters,Convergent Synthesis of α-Ketoamide Inhibitors of Pin1,"A convergent synthesis of alpha-ketoamide inhibitors of Pin1 is described. An alpha-hydroxyorthothioester derivative of Ser was reacted directly with an amine synthon. The reaction was catalyzed by HgO and HgCl(2) to form alpha-hydroxyamide. Thus, hydrolysis and coupling were combined in one step with 80% yield. Two diastereomers of a phospho-Ser-Pro alpha-ketoamide analogue were synthesized. The IC(50) values of 100 and 200 microM were surprisingly weak for Pin1 peptidyl prolyl isomerase.",10.1021/ol9027013,2010-01-26,0.598330124371833
Synthesis,A Convenient and Practical Synthesis of Aminopyrazoles,"A selective methodology for preparing highly substituted aminopyrazoles has been demonstrated. Starting with an acetophenol core, the corresponding substituted isoxazole is prepared in two steps. The isoxazole is transformed into a benzopyran. Alkylation of the aminobenzopyranone gives N-substituted aminobenzopyranone derivatives that react with substituted hydrazine to give aminopyrazoles. This versatile synthesis enables the preparation of highly substituted aminopyrazoles for use as key synthetic building blocks for biologically active molecules. In addition, this process represents the first amine alkylation of aminobenzopyranones.",10.1055/s-0034-1379474,2014-11-11,0.5983235614861846
Tetrahedron,A novel total synthesis of 11-oxygenated steroids,,10.1016/s0040-4039(01)89805-1,1967-01-01,0.5983161456243347
Organic Letters,Rapid Assembly of the Salvileucalin B Norcaradiene Core,Preparation of the polycyclic core of the cytotoxic natural product salvileucalin B is described. The key feature of this synthetic strategy is a copper-catalyzed intramolecular arene cyclopropanation to provide the central norcaradiene. These studies lay the foundation for continued investigations toward an enantioselective total synthesis of 1.,10.1021/ol902848k,2010-01-20,0.5983127040674265
Organic Letters,Total Synthesis of (−)- and (+)-Membrenone C,"[reaction: see text] A synthesis of the polypropionate marine defense substance (+)-membrenone C and its enantiomer that starts from (S)-2-methyl-3-(tert-butyldimethylsilyloxy)propanal is described. Key steps include (1) additions of chiral allenylmetal reagents to effect both chain homologation and the concomitant introduction of four stereo centers, (2) a bis-intramolecular hydrosilylation-oxidation sequence to install beta-hydroxy ketone subunits, and (3) a bis-intramolecular aldol reaction to construct the two dihydropyrone termini.",10.1021/ol034367v,2003-04-18,0.5983085358365569
Angewandte Chemie International Edition,A Concise Synthesis of Fumagillol,"A 13-step synthesis of (±)-fumagillol (1), the direct precursor of the potent angiogenesis inhibitors TNP-470 and fumagillin, from crotonaldehyde, diethylamine, and acrolein (see the scheme) has been achieved. The synthesis features a remarkable hetero-Claisen rearrangement. Small-molecule inhibitors of angiogenesis are promising chemotherapeutic agents for the treatment of cancer and inflammatory diseases.",10.1002/(sici)1521-3773(19990401)38:7<971::aid-anie971>3.0.co;2-w,1999-04-01,0.5983084339613196
Organic Letters,Total Synthesis of TAN1251C via Diastereoselective Construction of the Azaspiro Skeleton,An efficient total synthesis of TAN1251C was accomplished by employing a Ugi four-component accumulation reaction and a Dieckmann condensation to construct the spiro-fused cyclohexanone and γ-lactam ring. Diastereoselective reduction by side-chain-controlled hydrogenation of enamide 15 or Zn reduction of oxime 23 enabled construction of the amino group with the desired stereochemistry.,10.1021/acs.orglett.7b01718,2017-06-29,0.598302372641781
Angewandte Chemie International Edition,A Modular Approach to the Total Synthesis of Tunicamycins,"The tunicamycins constitute a delicate mimic of the bisubstrate intermediates of N-acetyl-D-hexosamine-1-phosphate translocases and thus inhibit bacterial cell-wall synthesis and the N glycosylation of eukaryotic proteins. An efficient approach to the synthesis of this unique type of nucleoside antibiotics is now reported and features the assembly of five modules in a highly stereoselective and robust manner. A Mukaiyama aldol reaction, intramolecular acetal formation, gold(I)-catalyzed O and N glycosylation, and final N acylation were used as the key steps.",10.1002/anie.201501890,2015-04-14,0.598299879513684
Tetrahedron,A new route to dithiirane 1-oxides: Oxidation of tetrathiolanes with dimethyldioxirane,,10.1016/s0040-4039(98)00522-x,1998-05-01,0.5982994287775196
Synthesis,"Use of Silyl Ester and Enamine Protection for an Efficient Alternate Synthesis of (1<i>S</i>,2<i>S</i>,5<i>R</i>,6<i>S</i>)-2-[(2′<i>S</i>)-(2′-Amino)propionyl]aminobicyclo[3.1.0]hexane-2,6-dicarboxylic Acid Hydrochloride (LY544344·HCl)","An alternate synthesis of title compound (5) using N-(2-methoxycarbonyl-1-methylvinyl)-l-alanine sodium salt (6) and 2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (1) was successfully completed. Incorporation of silyl ester protection and the use of an enamine-protecting group allowed for the elimination of several processing steps.",10.1055/s-2006-942487,2006-08-01,0.5982983045746538
Organic Letters,A Formal Synthesis of (±)-Arborisidine,"Herein, we report a formal synthesis of (±)-arborisidine via the creation of Jiao's intermediate with the critical caged structure. Starting from tryptamine, a Pictet-Spengler cyclization forged the piperidine ring, a Pd-catalyzed indole allylation and ring-closing metathesis protocol afforded a bridged aza-bicyclo[3.3.1]nonane moiety, and an intramolecular N-alkylation closed the final pyrrolidine ring. This study provides a new approach to the unique caged framework of arborisidine and relevant alkaloids.",10.1021/acs.orglett.4c00928,2024-04-26,0.5982862589991647
Angewandte Chemie International Edition,Total Synthesis of Vancomycin Aglycon—Part 2: Synthesis of Amino Acids 1–3 and Construction of the AB‐COD‐DOE Ring Skeleton,"A triazene-based synthetic strategy for the construction of the complex biaryl ethers and a Suzuki coupling reaction were the key steps in the synthesis of precursor 1 of the aglycon of vancomycin, which already contains the complete skeleton of the target compound. The cleavage of the triazene unit from the D ring and the removal of the other protecting groups led to the aglycon of vancomycin. These strategies should be particularly valuable for the synthesis of other naturally occurring glycopeptide antibiotics and offer opportunities for the synthesis of combinatorial libraries of compounds of the vancomycin family for chemical biology studies.",10.1002/(sici)1521-3773(19981016)37:19<2714::aid-anie2714>3.0.co;2-#,1998-10-16,0.5982728494957371
Organic Letters,Total Synthesis of (+)-Leucolusine and (−)-7-<i>epi</i>-Leucolusine,"Herein, we report the concise total syntheses of (+)-leucolusine and (−)-7- epi -leucolusine achieved in 8 steps starting from commercially available piperidin-2-one. Our strategy highlights a palladium-catalyzed decarboxylative asymmetric allylic alkylation for constructing the δ-lactam bearing a C20 all-carbon quaternary stereocenter. Additionally, the cis -fused octahydrofuro[2,3- b ]pyridine unit was efficiently constructed via a one-pot protocol encompassing reduction and oxa -Mannich-type cyclization processes.",10.1021/acs.orglett.5c01310,2025-05-02,0.5982699023323422
Journal of Organic Chemistry,Enantioselective Syntheses of (+)-Xylarenal A and <i>e</i><i>nt</i>-Xylarenal A,"[reaction: see text] The total synthesis of the sesquiterpenoid xylarenal A is reported. This first synthetic entry to an eremophilane terpenoid with an exocyclic vinyl aldehyde unit involves the use of the bicyclic enone (+)-3, which after a gamma-oxidation and alpha'-allylation leads to the formation of the ketone (+)-8. After its acylation, an oxidative cleavage of the allyl side chain followed by alpha-methylenation of the resulting aldehyde gives (+)-xylarenal A (1). The synthesis of (-)-xylarenal A from (-)-3 is also reported. Moreover, the first total synthesis of the trinoreremophilane (+)-1alpha-hydroxyisoondetianone (5) is described.",10.1021/jo0502450,2005-04-01,0.5982661327106895
Organic Letters,Stereoselective Synthesis of the Axially Chiral A−B Ring System of Vancomycin Utilizing a Planar Chiral Arene Chromium Complex,"[reaction: see text] The axial biaryl ring system of vancomycin was stereoselectively synthesized by utilizing a planar chiral tricarbonyl(arylhalide)chromium complex. Both enantiomers of the planar chiral (arylbromide)chromium complexes, (+)-9 and ent-(-)-9, can be stereoselectively transferred to an absolutely identical key intermediate 23 for the vancomycin A-B ring system by the diastereoselective Suzuki-Miyaura cross-coupling reaction as key step.",10.1021/ol010076f,2001-06-01,0.5982620172256199
Organic Letters,Synthesis of a P-Glycoprotein Inhibitor and Its High-Energy (<i>Z</i>)-Isomer by Carbenoid Eliminative Cross-Coupling,"To gauge the feasibility of carbenoid eliminative cross-coupling for the synthesis of polyfunctional alkenes, a P-glycoprotein inhibitor containing an ( E )-configured 4-chromanylidene-type trisubstituted olefin was prepared as well as its previously undescribed ( Z )-isomer. Stereospecific alkene synthesis required generation of functionalized enantioenriched α-metalated carbamates [R 1 R 2 CM(O 2 CN i -Pr 2 ), M = Li or Bneo], and problems associated with incorrect lithiation regioselectivity and unexpected organolithium configurational lability were encountered. Solutions to these difficulties are described together with a method for ee determination of α-carbamoyloxyboronates.",10.1021/acs.orglett.0c00755,2020-03-31,0.5982375962835095
Journal of Organic Chemistry,Synthesis of 5-<i>epi</i>-Taiwaniaquinone G,"A concise synthetic approach to the unnatural 5-epi-taiwaniaquinone G has been developed via a Lewis acid catalyzed tandem acylation-Nazarov cyclization reaction to construct the tricyclic skeleton, followed by installation of the isopropyl group through a strategy involving coumarin formation and its subsequent hydrolysis.",10.1021/jo500931e,2014-06-05,0.5982351863480412
Tetrahedron,"Highly selective synthesis of 2-substituted-5-hydroxy-6-oxo-1,6-dihydropyrimidine-4-carboxylic acid derivatives using a novel protected dihydroxyfumarate",,10.1016/j.tetlet.2004.06.028,2004-07-01,0.5982331680983916
Tetrahedron,Efficient route to optically pure polyfunctionalized cyclooctanes,,10.1016/s0040-4039(01)02126-8,2002-01-01,0.5982326778868481
Synthesis,Syntheses of 2-Chloro- and 2-Amino-5-fluoropyridines and Isolation of a Novel Difluoroboryl Imidate,"All articles of this category The highly volatile, weakly basic 2-chloro-5-fluoropyridine (3) , prepared by diazotization of 5-amino-2-chloropyridinc (1) with isoamyl nitrite/tetrafluoroboric acid followed by thermolysis (70%) has been characterized. Reaction of 3 with ammonia afforded a 3:1 mixture (40%) of 1 and 2-amino-5-fluoropyridine (4) . An alternate, 5-step synthesis gave 4 in 33% overall yield from 2-amino-5-nitropyridine (5) . One of the intermediates was shown to have a novel difluoroboryl imidate 10 structure.",10.1055/s-1989-27427,1989-01-01,0.5982305088899446
European Journal of Organic Chemistry,Synthetic Approaches to Anti‐Inflammatory Macrolactones of the Oxacyclododecindione Type,"Abstract Various synthetic approaches to the oxacyclododecindione‐type macrolactones, known for their potent anti‐inflammatory activity, are presented. These include an attempted carbonylative ring closure, a hydroacylation route, and an approach by ring‐closing metathesis and double bond isomerization, as well as a strategy including ring‐closing metathesis/unsaturation. The last route allowed the preparation of a bioactive analogue of the recently described 14‐deoxyoxacyclododecindione.",10.1002/ejoc.201500275,2015-04-21,0.5982266482363608
Synlett,A Short Enantioselective Synthesis of (S)-Levetiracetam through Direct Palladium-Catalyzed Asymmetric N-Allylation of Methyl 4-Aminobutyrate,"Abstract An exceedingly short and enantioselective synthesis of the antiepileptic drug (S)-levetiracetam was elaborated. As the chirogenic key step, a Pd-catalyzed asymmetric N-allylation of methyl 4-aminobutyrate was achieved in the presence of only 1 mol% of a catalyst prepared in situ from [Pd(allyl)Cl]2 and a tartaric acid-derived C 2-symmetric diphosphine ligand.",10.1055/a-1493-9078,2021-04-28,0.5982213132483555
Organic Letters,Synthetic Studies on (+)-Naphthyridinomycin:  Stereoselective Synthesis of the Tetracyclic Core Framework,"[reaction: see text] The stereoselective synthesis of the tetracyclic intermediate 21 for (+)-naphthyridinomycin (1) has been accomplished. The convergent synthesis used the Ugi 4CC reaction with the amine derivative 10. The key features of the stereoselective synthesis of 21 were the intramolecular Mizoroki-Heck reaction, an aromatic-aldehyde cyclization, and a stereoselective hydroboration.",10.1021/ol048857e,2004-08-13,0.5981942665296724
Synlett,Progress toward the Synthesis of Sarain A,"All articles of this category In this Account we describe our efforts over more than five years to find a synthetic route to saran A ( 1 ), a complex marine alkaloid. The basic synthetic plan (Scheme 1) calls for construction of the tricyclic ”core”, annulation of the saturated 13-membered ring, and finally, annulation of the unsaturated 14-membered ring. Synthesis of the core has almost been achieved, and a suitable route has been found to lactam 103 , a model for the unsaturated 14-membered ring in sarain A. alkaloids - 1,3-dipolar cycloaddition - azomethine ylide",10.1055/s-1995-5298,1995-06-01,0.5981892033614996
Tetrahedron,"Synthesis of (7E,9Z)-7,9-dodecadien-1-yl acetate, a sex pheromone of lobesia botrana",,10.1016/s0040-4039(00)91150-x,1975-01-01,0.5981857755866571
Journal of the American Chemical Society,Enantioselective Synthesis of Carbo- and Heterocycles through a CuH-Catalyzed Hydroalkylation Approach,"The enantioselective, intramolecular hydroalkylation of halide-tethered styrenes has been achieved through a copper hydride-catalyzed process. This approach allowed for the synthesis of enantioenriched cyclobutanes, cyclopentanes, indanes, and six-membered N- and O-heterocycles. This protocol was applied to the synthesis of the commercial serotonin reuptake inhibitor (-)-paroxetine.",10.1021/jacs.5b07061,2015-08-09,0.5981844321464068
Journal of Organic Chemistry,Total Synthesis of (±)-Stemodinone via an Efficient Ring-Exchange Strategy,"A total synthesis of (+/-)-stemodinone, a tetracyclic stemodane diterpene, from the known tricyclic methyl olefin 11 is described. The key steps involve an efficient ring-exchange reaction and palladium(0)-catalyzed lactone migration. The ring-exchange strategy for controlling the stereochemistry was based on an initial Diels-Alder reaction to form a new ring followed by cleavage of the original ring. Cleavage of the original ring of the Diels-Alder adduct 9 was achieved by an initial regio- and chemoselective Baeyer-Villiger oxidation followed by the Pd(0)-catalyzed lactone-migration reaction reported by us.",10.1021/jo015808w,2001-09-26,0.5981839161538929
Synlett,Regiospecific Synthesis of the C and D Rings of Viridin,An eight-step regiospecific synthesis of the C and D rings of viridin is reported using an intramolecular Diels-Alder reaction of a furan diene as the key step.,10.1055/s-2008-1072651,2008-04-25,0.5981837908553347
Tetrahedron,A chiral bicyclic intermediate for the synthesis of forskolin,,10.1016/s0040-4039(00)96023-4,1987-01-01,0.5981831112762211
Synthesis,Total Synthesis of the Proposed Structures of the Novel Antimalarial Pyranone Cryptorigidifoliol E,"The total syntheses of the proposed structures of the antimalarial lactone cryptorigidifoliol E are described. The synthetic sequence notably features a Bartlett–Smith halocyclization to give a chiral epoxide, followed by its regioselective ring-opening reaction, Still–Gennari­ olefination, Corey–Bakshi–Shibata (CBS) ynone reduction, and olefin cross-metathesis.",10.1055/s-0035-1562778,2016-08-02,0.5981798144982395
Synthesis,Synthesis of Polyhydroxylated Pyrrolidines and Aziridinopyrrolidines from [4π+2π] Cycloadducts of Cyclopentadiene and Imines/2<i>H</i>-Azirines,"The synthesis of 2-functionalized 3,5-bis(hydroxymethyl)pyrrolidines from readily available polycyclic Diels-Alder adducts by a reaction sequence involving three steps is described. The same methodology has been applied to obtain the aziridine counterparts from the corresponding methyl 2-azatricyclo[3.2.1.02,4]oct-6-ene-4-carboxylates. The key steps in the synthetic strategy are dihydroxylation with osmium tetroxide/N-methylmorpholine N-oxide, oxidative cleavage with sodium periodate, and reduction using sodium borohydride or lithium aluminum hydride; overall yields ranged from 40-60%.",10.1055/s-2008-1032196,2008-03-01,0.598173205062686
Organic Process Research & Development,"Synthesis of Filibuvir. Part I. Diastereoselective Preparation of a β-Hydroxy Alkynyl Oxazolidinone and Conversion to a 6,6-Disubstituted 2<i>H</i>-Pyranone","This is the first in a series of three papers describing the identification and development of a commercial synthesis of filibuvir ( 1 ). This contribution describes development of an Evans aldol reaction to control the tertiary alcohol stereocenter, a challenging variant of that strategy in that both reacting partners were nonstandard (acetate enolate and ketone electrophile). A sequence consisting of Sonogashira coupling, acylation and hydrogenation delivered acetate 24, and Dieckmann cyclization provided β-keto lactone 2 .",10.1021/op4002356,2013-11-26,0.598162352626819
Tetrahedron,"Synthesis, structure and properties of N -aminosaccharin – A selective inhibitor of human carbonic anhydrase I",,10.1016/j.tetlet.2016.12.005,2016-12-05,0.5981560053152304
Synthesis,"A Facile Route to Pyrrolo[3′,4′:3,4]pyrido[1,2-<i>a</i>]benzimidazoles, Novel Heterocyclic Derivatives","The title system derivatives were prepared in two steps. Thus the condensation of 2-benzimidazoleacetonitrile with ethyl 4-chloro-3-oxobutanoate led to the 3-chloromethyl-1,5-dihydro-1-oxo­pyrido[1,2-a]benzimidazole-4-carbonitrile. Further amination of the obtained chloronitrile with primary amines yielded 1-amino-2,3-dihydro-2-R-5H-pyrrolo[3′,4′:3,4]pyrido[1,2-a]benzimidazol-5-ones.",10.1055/s-2004-815950,2004-01-01,0.5981535522979979
Organic Process Research & Development,Concise Synthesis of Key Intermediates of Pyriftalid and Paquinimod via Hydrogenation Method,"An efficient and scalable synthesis of 7-amino-3-methylisobenzofuran-1(3 H )-one ( 1 ) and 2-amino-6-ethylbenzoic acid ( 2 ) has been developed via a one-step catalytic hydrogenation. The triethylammonium salt of 2-acetyl-6-nitrobenzoic acid was used as the starting material and 1 was prepared in a biphasic solvent system of toluene/H 2 O, while 2 was obtained when the solvent was replaced with H 2 O. Intermediates 1 and 2 could be used to synthesize Pyriftalid and Paquinimod, respectively.",10.1021/acs.oprd.7b00177,2017-08-21,0.5981398855764309
Tetrahedron,"Corrigendum to “First asymmetric synthesis of (2R,3R)-3-amino-1-benzyl-2-methylpyrrolidine via a highly diastereoselective reductive alkylation”",,10.1016/s0040-4039(00)01863-3,2001-01-01,0.5981363210241843
Organic Letters,"Synthesis of 1,2-<i>trans</i>-2-Acetamido-2-deoxyhomoiminosugars","The first synthesis of 1,2-trans-homoiminosugars devised as mimics of β-D-GlcNAc and α-D-ManNAc is described. Key steps include a regioselective azidolysis of a cyclic sulfite and a β-amino alcohol skeletal rearrangement applied to a polyhydroxylated azepane. The β-D-GlcNAc derivative has been coupled to serine to deliver an iminosugar C-amino acid. The two homoiminosugars demonstrate moderate glycosidase inhibition.",10.1021/ol502929h,2014-10-20,0.5981326152196942
European Journal of Organic Chemistry,First Total Synthesis of Original Chalcone–Flavone Dimers as Cissampeloflavone Analogues,"The total synthesis of furoflavones closely related to the natural product cissampeloflavone was explored following different pathways. The involvement of a flavone as a key intermediate proved to be the most efficient way to form the 7‐phenyl‐5 H ‐furo[3,2‐ g ]chromen‐5‐one scaffold, and the first example of furoflavone formation was achieved in this way. For the synthesis of chalcone–flavone dimers, two different strategies were examined: either acylation at the very end of the synthesis, or introduction of the 3‐acyl group during furan‐ring formation. The final acylation was hardly achievable with hindered benzoyl chlorides, but a simpler 4‐methoxybenzoyl group was added to the furoflavone in modest yield. The alternative direct introduction of this acyl group during furan formation proved to be more efficient. Conjugate addition of an iodoflavone to an ynone followed by intramolecular Heck cyclization gave the best results, leading to the first synthetic chalcone–flavone dimer ever described.",10.1002/ejoc.201800338,2018-04-24,0.5981258492127929
Tetrahedron,Synthesis of ketene phenyltelluroacetals by a Wittig-Horner route,,10.1016/0040-4039(95)01656-2,1995-10-01,0.5981251690158831
Tetrahedron,Synthesis of R-laudanosine and 9-R-O-methylflavinantine by asymmetric alkylation,,10.1016/s0040-4039(00)80079-9,1988-01-01,0.5981213278921106
Journal of the American Chemical Society,Asymmetric Total Synthesis of <i>e</i><i>nt</i>-(−)-Roseophilin:  Assignment of Absolute Configuration,"An asymmetric total synthesis of ent-(-)-roseophilin (1), the unnatural enantiomer of a novel naturally occurring antitumor antibiotic, is described. The approach enlists a room temperature heterocyclic azadiene inverse electron demand Diels-Alder reaction of dimethyl 1,2,4,5-tetrazine-3,6-dicarboxylate (7) with the optically active enol ether 6 bearing the C23 chiral center followed by a reductive ring contraction reaction for formation of an appropriately functionalized pyrrole ring in a key 1,2,4,5-tetrazine --> 1,2-diazine --> pyrrole reaction sequence. A Grubbs' ring closing metathesis reaction was utilized to close the unusual 13-membered macrocycle prior to a subsequent 5-exo-trig acyl radical-alkene cyclization that was used to introduce the fused cyclopentanone and complete the preparation of the tricylic ansa-bridged azafulvene core 32. Condensation of 32 with 33 under the modified conditions of Tius and Harrington followed by final deprotection provided (22S,23S)-1. Comparison of synthetic (22S,23S)-1 ([alpha](25)(D), CD) with natural 1 established that they were enantiomers and enabled the assignment of the absolute stereochemistry of the natural product as 22R,23R. Surprisingly, ent-(-)-1 was found to be 2-10-fold more potent than natural (+)-1 in cytotoxic assays, providing an unusually rewarding culmination to synthetic efforts that provided the unnatural enantiomer.",10.1021/ja011271s,2001-08-10,0.5981086267780249
Synlett,Divergent Total Syntheses of Six Ganoderma Meroterpenoids: A Bioinspired Two-Phase Strategy,"We briefly highlight our recent work on the total synthesis of six Ganoderma phenolic meroterpenoids: ganocins A–C, ganocochlearins A–D, and cochlearol T. Critical to this success was a bioinspired two-phase strategy that featured an early-stage rapid construction of a common planar tricyclic intermediate and late-stage highly selective transformations of this intermediate into various Ganoderma meroterpenoids. Key steps of the synthesis include a biomimetic ortho-quinone methide intramolecular hetero-Diels–Alder reaction, a Stahl-type oxidative aromatization, a nucleophilic dearomatization of a phenol, a regioselective 1,4-reduction of a dienone, a site-selective Mukaiyama hydration, and an intramolecular oxa-Michael addition/triflation cascade.",10.1055/s-0040-1707898,2020-07-20,0.5981084742470691
Tetrahedron,Improved enantioselective synthesis of anti α-methyl-β-hydroxyesters through TiCl4-PPh3 mediated aldol condensation,,10.1016/s0040-4039(00)84360-9,1986-01-01,0.5981079261813813
Tetrahedron,Chiral dithiolane sulphoxides: An efficient stereoselective synthesis of (R) and (S)-3-benzoyloxy-2-butanone,,10.1016/0040-4039(95)01280-u,1995-09-01,0.5980999723334757
Tetrahedron,Total synthesis of 19(RS)-F-LTA4 methyl ester,,10.1016/0040-4039(95)01271-i,1995-09-01,0.5980997990593804
Tetrahedron,Synthesis of highly soluble fluorescent π-extended 2-(2-thienyl)benzothiazole derivatives via oxidative cyclization of 2-thienylthioanilide as the key step,,10.1016/j.tetlet.2013.10.071,2013-10-30,0.5980908804699079
Journal of Organic Chemistry,Alkylation of Hagemann's ester. Preparation of an intermediate for trisporic acid synthesis,NRC publication: Yes,10.1021/jo00930a001,1974-08-01,0.5980895743593334
Organic Process Research & Development,Development of the Commercial Route for the Manufacture of a 5-Lipoxygenase Inhibitor PF-04191834,"A de novo three-step-one-pot process for the formation of PF-04191834 was developed. This methodology employed inexpensive, odorless, and readily available commodity chemical iso-octyl-3-mercaptopropionate as a sulfur source, which could be a general alternative to the popular TIPS-SH in the formation of diarylthioethers via Migita coupling. A kinetic study revealed that, at high temperature, reductive elimination could be the rate-limiting step in the catalytic cycle, which opens pathways for the generation of undesired impurities. By proper control of the reaction conditions, the desired API was synthesized in >70% crude yield and in 55% isolated yield after vigorous purifications. This process was successfully demonstrated on a 20 kg scale.",10.1021/op500412a,2015-07-17,0.5980888631285307
Tetrahedron,Carbocycles from carbohydrates: A simple route to an enantiomerically pure prostaglandin intermediate,,10.1016/s0040-4039(00)80802-3,1988-01-01,0.5980884792467115
Journal of the American Chemical Society,Spirodiepoxides in Total Synthesis:  Epoxomicin,"The first use of the spirodiepoxide functional group in total synthesis, a study culminating in an efficient synthesis of the potent proteasome inhibitor epoxomicin, is described. Spirodiepoxides derived from allenes by oxidation are shown to give syn disubstituted ketones and their derivatives, including ortho ester, oxazoline, azido epoxide, as well as sulfonamide-, amide-, and azide-containing hydroxy ketones.",10.1021/ja044563c,2004-11-04,0.598087171247548
Synthesis,Total Synthesis of Vestitol and Medicarpin,"Abstract Total synthesis of vestitol and medicarpin, two isoflavonoids with distinct skeletons, was successfully achieved using a single intermediate as the starting point. This six-step synthetic approach features a BBr3-promoted tandem O-demethylation/cyclization reaction, which enables the rapid construction of the pterocarpan core structure. Subsequently, a Pd/C-catalyzed hydrogenation/hydrogenolysis reaction was employed to respectively synthesize vestitol and medicarpin.",10.1055/a-2705-4229,2025-09-19,0.5980762322711509
Tetrahedron,A catalytic dehydrogenation route to azomethine imines.,,10.1016/s0040-4039(00)94694-x,1990-01-01,0.5980744864915423
Journal of Organic Chemistry,Total Synthesis and Biological Evaluation of Neodysiherbaine A and Analogues,"Dysiherbaine (1) and its congener neodysiherbaine A (2) are naturally occurring excitatory amino acids with selective and potent agonistic activity for ionotropic glutamate receptors. We describe herein the total synthesis of 2 and its structural analogues 3-8. Advanced key intermediate 16 was employed as a branching point to assemble a series of these analogues 3-8 with respect to the C8 and C9 functionalities, which would not have been accessible through manipulations of the natural product itself. The synthesis of key intermediate 16 features (i) stereocontrolled C-glycosylation to set the C6 stereocenter, (ii) concise synthesis of the bicyclic ether skeleton through chemo- and stereoselective dihydroxylation of the exo-olefin and stereoselective epoxidation of the endo-olefin, followed by epoxide ring opening/5-exo ring closure, and (iii) catalytic asymmetric hydrogenation of enamide ester to construct the amino acid appendage. A preliminary biological evaluation of analogues for their in vivo toxicity against mice and binding affinity for glutamate receptors showed that both the type and stereochemistry of the C8 and C9 functional groups affected the subtype selectivity of dysiherbaine analogues for members of the kainic acid receptor family.",10.1021/jo0605593,2006-06-17,0.598068910830023
Angewandte Chemie International Edition,Asymmetric Total Synthesis of Brasilicardins,"Brasilicardins, bacterial diterpenoid natural products that display highly potent immunosuppressive activity, are promising immunosuppressant drug candidates. Structurally, they can be described as hybrids of terpenoids, amino acids, and saccharides, and share a characteristic highly strained anti-syn-anti-fused perhydrophenanthrene terpenoid scaffold (ABC-ring system) with two quaternary asymmetric carbon atoms. A unified and stereoselective total synthesis of all four brasilicardins has been designed based on the strategic use of an intramolecular conjugate addition. The ABC-ring system was initially constructed with high stereocontrol by novel intramolecular conjugate additions of Weinreb amides and in situ generated (Z)-vinyl copper species. The late-stage common intermediate was subjected to stereoselective installation of the amino acid component, followed by introduction of the saccharide unit via glycosylation to accomplish the total synthesis of brasilicardins A-D. Our synthesis offers opportunities to synthesize various brasilicardin analogues for biological and pharmacological investigations.",10.1002/anie.201811403,2018-11-01,0.5980661737852252
Tetrahedron,Synthetic studies on quassinoids: total synthesis of (±)-glaucarubolone and (±)-holacanthone,,10.1016/s0040-4039(00)74149-9,1992-03-01,0.5980656877424991
Tetrahedron,Synthetic studies on prostanoids V. Total synthesis of prostaglandin E1 and F1β,,10.1016/s0040-4039(00)75009-x,1975-01-01,0.5980656877424991
Tetrahedron,Synthetic studies on quassinoids: Total synthesis of (±)-amarolide,,10.1016/s0040-4039(00)95748-4,1987-01-01,0.5980656877424991
Tetrahedron,Synthetic studies on concanamycin A: Total synthesis of concanolide A (concanamycin F),,10.1016/s0040-4039(98)01234-9,1998-08-01,0.5980656877424991
Tetrahedron,Synthetic studies towards oxylipins: total synthesis of Constanolactones A and B,,10.1016/s0040-4039(00)00343-9,2000-04-01,0.5980656877424991
Tetrahedron,Phyllanthoside-Phyllanthostatin synthetic studies. 6. An augmented spiroketalization tactic for the total synthesis of phyllanthocin,,10.1016/s0040-4039(00)70688-5,1989-01-01,0.5980656877424991
Journal of Organic Chemistry,Asymmetric Synthesis of Natural and Unnatural Dibenzylbutane Lignans from a Common Intermediate,"Lignans are a structurally diverse class of natural products with extensive pharmacological effects. Here we report the syntheses of both natural and unnatural dibenzylbutane lignans from a common intermediate, which is prepared in five steps from known materials. Derivatization of this intermediate affords lignans featuring contiguous stereocenters in a high diastereomeric purity after chromatography. This divergent synthetic route can be exploited to prepare dibenzylbutane lignans and analogues thereof to probe their biological profiles.",10.1021/acs.joc.9b00633,2019-04-19,0.5980521215029934
Tetrahedron,"A novel synthesis of N-(piperidin-4-yl)-1,3-dihydroindol-2-one via an intramolecular Pd-catalyzed amination",,10.1016/j.tetlet.2004.09.121,2004-10-05,0.5980509533417747
Tetrahedron,Convergent synthesis of the FGHI ring system of yessotoxin: stereoselective construction of the G ring,,10.1016/j.tetlet.2005.04.040,2005-04-28,0.5980489636838281
Synlett,Synthesis of Unsymmetrical Methylenebisphenol Derivatives,"A simple and efficient route towards unsymmetrical methylenebisphenol derivatives is reported. This straightforward strategy avoids the use of harmful or dangerous chemicals, allowing the synthesis of highly functionalized bisphenyls with no need of protecting groups. The alkylation of the phenyl ring is selective for the para position of the hydroxyl substituent. All methylenebisphenols were obtained in a completely regioselective manner and isolated in high yields.",10.1055/s-0032-1318394,2013-03-06,0.5980445661084428
Chemical Science,Asymmetric synthesis of chiral β-alkynyl carbonyl and sulfonyl derivatives via sequential palladium and copper catalysis,"We present a full account detailing the development of a sequential catalysis strategy for the synthesis of chiral β-alkynyl carbonyl and sulfonyl derivatives. A palladium-catalyzed cross coupling of terminal alkyne donors with acetylenic ester, ketone, and sulfone acceptors generates stereodefined enynes in high yield. These compounds are engaged in an unprecedented, regio- and enantioselective copper-catalyzed conjugate reduction. The process exhibits a high functional group tolerance, and this enables the synthesis of a broad range of chiral products from simple, readily available alkyne precursors. The utility of the method is demonstrated through the elaboration of the chiral β-alkynyl products into a variety of different molecular scaffolds. Its value in complex molecule synthesis is further validated through a concise, enantioselective synthesis of AMG 837, a potent GPR40 receptor agonist.",10.1039/c6sc01724j,2016-01-01,0.5980440695611168
Tetrahedron,Synthetic studies toward merrilactone A: a short synthesis of AB ring motif,,10.1016/j.tetlet.2005.08.116,2005-09-10,0.5980329898712332
Tetrahedron,Isolation and total synthesis of two novel metabolites from the fissurellid mollusc Scutus antipodes,,10.1016/j.tetlet.2017.01.096,2017-01-28,0.5980301833285481
Organic Letters,Synthesis of the BCD Tricyclic Core of Densanins A and B,A substrate stereocontrolled synthesis of the BCD tricyclic ring system of densanins A and B has been developed. The key transformations include the assembling of ring B via an unprecedented tandem N-allylation/SN2' reaction and the construction of ring C via gold-catalyzed alkenylation of terminal alkyne and pyrrole.,10.1021/acs.orglett.6b00606,2016-04-11,0.5980292213764588
Tetrahedron,A convenient new route to cyclopropanol derivatives,,10.1016/0040-4039(70)89008-6,1970-01-01,0.5980263485394364
Tetrahedron,"Novel synthesis of trioxatetracyclo[5.3.2.0.4,9.04,11]dodecane and bibenzyl skeletons",,10.1016/s0040-4039(97)10858-9,1998-03-01,0.5980091791898534
Angewandte Chemie International Edition,Bioinspired Total Synthesis of Pyritide A2 through Pyridine Ring Synthesis,"Pyritides belong to the ribosomally synthesized and post-translationally modified peptide class of natural products that were recently genome-predicted and are structurally defined by unique pyridine-containing macrocycles. Inspired by their biosynthesis, proceeding through peptide modification and cycloaddition to form the heterocyclic core, we report the chemical synthesis of pyritide A2 involving pyridine ring synthesis from an amino acid precursor through aza-Diels-Alder reaction. This strategy permitted the preparation of the decorated pyridine core with an appended amino acid residue in two steps from a commercially available arginine derivative and secured pyritide A2 in ten steps. Moreover, the synthetic logic enables efficient preparation of different pyridine subunits associated with pyritides, allowing rapid and convergent access to this new class of natural products and analogues thereof.",10.1002/anie.202212299,2022-09-20,0.5980007103365279
Tetrahedron,Synthesis of intermediates for the preparation of core analogs of esperamicin,,10.1016/0040-4039(95)00894-i,1995-07-01,0.5979987466161464
Tetrahedron,Synthesis of Intermediates for the Preparation of Core Analogs of Esperamicin,,10.1016/00404-0399(50)0894i-,1995-07-10,0.5979987466161464
Organic Letters,A Convergent Synthesis of the Fully Elaborated Macrocyclic Core of TMC-95A,A concise and straightforward synthesis of the fully elaborated macrocyclic core of TMC-95A is reported. A highly efficient organocatalyzed aldolization between isatin and dihydroxyacetone derivatives and formation of the biaryl subunit with concomitant macrocyclization are the characteristic features of this synthesis.,10.1021/ol403675c,2014-02-21,0.5979974046675264
Tetrahedron,Layered compounds. XXV. Peropyrene and teropyrene -a new synthetic route of pyrene-like polynuclear aromatic hydrocarbons-,,10.1016/s0040-4039(00)72628-1,1975-01-01,0.5979959517506604
Journal of Organic Chemistry,Synthesis of Unusual <i>N</i>-Acylated Aminosugar Fragments of <i>Mycobacterium marinum</i> Lipooligosaccharide IV,"A convergent strategy was developed for the stereoselective synthesis of four unusual N-acylated monosaccharides (5-8), which are fragments of lipooligosaccharide IV (LOS-IV) from Mycobacterium marinum. A critical substrate-controlled asymmetric cyclization of an amino acid derived oxazolidine provided a key lactam intermediate 11, which was successfully converted to targets 5-7. The key step in the synthesis of 8 was a one-pot cascade oxidation-cyclization-oxidation reaction of a Boc-protected amino alcohol, prepared from 3-butynol, which led to the formation of lactam 15. The five-membered ring lactam intermediates in these synthetic routes were sensitive to elimination side reactions, but careful manipulation of the reaction sequence allowed for the stereoselective synthesis of the targets. This work represents the first synthesis of these unusual motifs, which have been shown to be essential to the bioactivity of LOS-IV.",10.1021/acs.joc.5b00064,2015-02-02,0.5979892713466278
Organic Letters,Divergent Total Syntheses of Isobatzellines A/B and Batzelline A,"Divergent total syntheses of isobatzellines A/B and batzelline A were accomplished. A fully substituted common indole intermediate bearing C-2 methylthio and C-5 chloro groups was constructed via ring expansion of benzocyclobutenone oxime sulfonate with NaSMe and a benzyne-mediated cyclization/functionalization sequence as the key steps. The total synthesis of isobatzelline B was achieved via formation of the iminoquinone structure by the redox-neutral acid-promoted C-5 proto-dechlorination of the common indole intermediate. The total syntheses of isobatzelline A and batzelline A were completed in a divergent manner by oxidation of the common indole intermediate using MnO 2 or Mn(OAc) 3, respectively.",10.1021/acs.orglett.0c01894,2020-07-05,0.5979820396148117
Synlett,"Stereoselective Total Synthesis of (-)-α-Eudesmol, a P/Q-Type Calcium Channel Blocker","All articles of this category Practical and stereoselective total synthesis of (-)-α-eudesmol 1 , a P/Q-type calcium channel blocker, has been achieved with the key step being a cyclopropane ring opening accompanying introduction of a hydroxyl group. (+)-Carissone is used as a key intermediate. α-eudesmol - natural products - total synthesis - stereoselective - ring opening",10.1055/s-2001-16804,2001-01-01,0.5979751734190952
Journal of Organic Chemistry,"Organocatalytic Approach for Short Asymmetric Synthesis of (<i>R</i>)-Paraconyl Alcohol: Application to the Total Syntheses of IM-2, SCB2, and A-Factor γ-Butyrolactone Autoregulators","( R)-Paraconyl alcohol is found to be a key intermediate for the syntheses of many γ-butyrolactone autoregulators. The chiral auxiliary approach and enzymatic resolution are the two common strategies employed so far in the literature for the asymmetric synthesis of ( R)-paraconyl alcohol. Herein, we report the first organocatalytic approach for the short asymmetric synthesis of ( R)-paraconyl alcohol in four steps and by a single column purification. Asymmetric syntheses of IM-2, SCB2, and A-factor γ-butyrolactone autoregulators were achieved from ( R)-paraconyl alcohol in three steps.",10.1021/acs.joc.8b00122,2018-02-28,0.5979736210221084
Organic Letters,De Novo Asymmetric Synthesis and Biological Evaluation of the Trisaccharide Portion of PI-080 and Vineomycin B2,"A highly enantio- and diastereoselective synthesis of an alpha-L-aculose, alpha-L-rhodinose, and beta-D-olivose trisaccharide is described. The key transformations include the palladium-catalyzed glycosylation, Myers' reductive rearrangement, diastereoselective dihydroxylation, and regioselective Mitsunobu inversion. Significant apoptotic antitumor activity was found for this trisaccharide, which has implication for vineomycin B2 and PI-080 structure-activity relationship.",10.1021/ol801817f,2008-09-12,0.5979705843442793
Synlett,One-Pot Palladium-Catalyzed Synthesis of Benzo[b]carbazolediones,"A palladium-catalyzed one-pot reaction for the synthesis of benzo[ b ]carbazolediones is described which proceeds by amination of 2,3-dibromonaphthoquinone, Suzuki cross-coupling with (2-bromo­phenyl)boronic acid, and subsequent intramolecular C–N Buchwald–Hartwig cyclization with amines.",10.1055/s-0035-1560212,2015-09-23,0.5979695988970511
Synlett,"Short Total Synthesis of Aspartyl Protease Inhibitors L-685,434, L-682,679 and L-685,458","Hydroxyethylene dipeptide isosteres L-685,434, L-682,679 and L-685,458 were synthesized in a few steps by a sequence involving an allyltrichlorostannane coupling with an α-aminoaldehyde followed by hydroboration of the corresponding 1,2-syn and 1,2-anti aminoalcohols to give the diols, lactonization under TPAP conditions, lactone opening and peptide coupling with the desired amine or dipeptide amide.",10.1055/s-2002-34891,2002-01-01,0.5979637780138756
Organic Letters,Enantiopure α-Trifluoromethylated Aziridine-2-carboxylic Acid (α-TfmAzy): Synthesis and Peptide Coupling,A straightforward synthesis of enantiopure α-trifluoromethyl aziridine-2-carboxylic acid (α-TfmAzy) is reported from a trifluoropyruvate derived enantiopure oxazolidine. A key Strecker-type synthetic step and a late cyanide basic hydrolysis gave the target compounds in six steps and 41% yield. A final peptide coupling was performed to demonstrate the usefulness of this highly constrained fluorinated unnatural amino acid.,10.1021/acs.orglett.0c00645,2020-03-27,0.597963080194575
Journal of Organic Chemistry,"Step-Economic Synthesis of (+)-Crocacin C: A Concise Crotylboronation/[3,3]-Sigmatropic Rearrangement Approach",The step-economic total synthesis of (+)-crocacin C has been achieved in 20% yield from commercially available starting materials. This approach requires the isolation of only 8 intermediates and can provide a reliable supply of (+)-crocacin C for the development of new antifungal and crop protection agents.,10.1021/jo301210f,2012-07-18,0.5979560854383095
Synlett,"Efficient Preparation of 2-Substituted Pyridazino[4,3-<i>h</i>]psoralen Derivatives","An efficient synthesis of 2-chloro-6-methoxypyridazino[4,3-h]psoralen was achieved by Diels-Alder reaction of 3,6-dichloro-1,2,4,5-tetrazine and 8-methoxy-psoralen (8-MOP) in a one-pot procedure. The convenient transformation of this intermediate into the 2-triflate derivative allowed efficient palladium-catalyzed reduction, methoxycarbonylation , and Sonogashira cross-coupling reactions at C2.",10.1055/s-2003-42070,2003-01-01,0.5979559137886303
Synthesis,Synthesis of 5-Amino-4-aminocarbonyl-1-hydroxyimidazole and its Conversion to Novel Acyclic Analogues of AICA Riboside,"All articles of this category A new, improved procedure for the preparation of 5-amino-4- aminocarbonyl-1-hydroxyimidazole from N ′-benzyloxy- N,N - dimethylformamidine and 2-amino-2-cyanoacetamide is described. O -Alkylation of this 1-hydroxyimidazole with appropriately functionalised alkyl halides or sulphonates provides an efficient route to acyclic imidazole nucleoside analogues.",10.1055/s-1990-27045,1990-01-01,0.5979554847278495
Journal of the American Chemical Society,Total Synthesis and Stereochemical Assignment of the Salicylate Antitumor Macrolide Lobatamide C,The total synthesis and stereochemical assignment of the potent antitumor macrolide lobatamide C is reported. The synthesis involves Cu(I)-mediated enamide formation and Na(2)CO(3)-mediated esterification of a beta-hydroxy acid and a salicylate cyanomethyl ester. Macrolactonization was accomplished using a Mitsunobu protocol. The stereochemical assignment of lobatamide C was achieved by Mosher ester analysis and comparison with prepared stereoisomers.,10.1021/ja026025a,2002-04-24,0.5979545880549382
Tetrahedron,Novel route to the synthesis of hydroxylated piperidine and pyrrolidine derivatives via the intramolecular reaction of γ-aminoallylstannane with aldehyde,,10.1016/0040-4039(96)00205-5,1996-03-01,0.5979491578538475
Organic Letters,Synthesis of Ecteinascidin ET-743 and Phthalascidin Pt-650 from Cyanosafracin B,"An efficient new process is described for the synthesis of ecteinascidin ET-743 (1) and phthalascidin (2), starting from readily available cyanosafracin B (3).",10.1021/ol0062502,2000-07-19,0.5979458947964759
Tetrahedron,An enantioselective approach to trehazolin: a concise and efficient synthesis of the aminocyclopentitol core,,10.1016/s0040-4039(00)02314-5,2001-02-01,0.5979386906120514
Journal of Organic Chemistry,"An Efficient, General Asymmetric Synthesis of Carbocyclic Nucleosides:  Application of an Asymmetric Aldol/Ring-Closing Metathesis Strategy","A general and efficient synthesis of carbocyclic and hexenopyranosyl nucleosides has been developed. The strategy combines three key transformations: an asymmetric aldol addition to establish the relative and absolute configuration of the pseudosugar, a ring-closing metathesis to construct the pseudosugar ring, and a Trost-type palladium(0)-mediated substitution to assemble the pseudosugar and the aromatic base. Carbovir, abacavir, and their 2'-methyl derivatives as well as hexenopyranosyl nucleoside analogues have been prepared by this sequence.",10.1021/jo005535p,2000-11-17,0.5979270426695789
Angewandte Chemie International Edition,Total Synthesis of Pectenotoxin‐2,"Pectenotoxin-2 (PTX2) is a shellfish toxin and has a non-anomeric spiroacetal, which is not stabilized by an anomeric effect. The selective construction of the non-anomeric spiroacetal has been a major problem in the synthesis of PTX2. Described herein is the stereoselective total synthesis of PTX2 via the isomerization of anomeric spiroacetal pectenotoxin-2b (PTX2b). The synthesis of PTX2b was achieved by a simple process including sulfone-mediated assembly of spirocyclic and bicyclic acetals and subsequent macrocyclization by ring-closing olefin metathesis. Finally, the selective construction of PTX2 was accomplished by the early termination of a dynamic transition process to equilibrium in the acid-catalyzed isomerization of anomeric PTX2b. [6,6]-Spiroacetal pectenotoxin-2c (PTX2c) was also synthesized from PTX2b. The cytotoxicity assay of the synthetic compounds against HepG2 and Caco2 cancer cells showed a potency of the order: PTX2≫PTX2b>PTX2c.",10.1002/anie.201308502,2013-11-29,0.597921859588466
Synlett,"Synthesis of 4-Hydroxy-3-Substituted Indoles and Indolequinones via an 3-Acetyloxy-4-oxo-4,5,6,7-tetrahydroindole Intermediate","All articles of this category The synthesis of 3-benzyloxycarbonyl-4-hydroxyindole ( 6 ) and indolequinones 7a,b from a common-3-acetyloxy-4-oxo-4,5,6,7-tetrahydroindole intermediate 3 is described. A one-step conversion of 3 into 3-trifluoromethanesulfonyloxytetrahydroindole 4 is highlighted and provides a versatile intermediate which undergoes mild palladium-catalyzed carbonylations. Successive oxidations provided the indolequinones 7a,b . 3-Acetyloxy-4-oxo-tetrahydroindole - 4-Hydroxyindole - Indolequinones - Carbonylation",10.1055/s-1995-4874,1995-01-01,0.5979210809194196
Tetrahedron,Asymmetric synthesis of ibuprofen via diastereoselective alkylation of a homochiral N-acylbornanesultam,,10.1016/s0040-4039(97)00148-2,1997-03-01,0.5979192696333192
Organic Letters,Asymmetric Total Synthesis of (<i>S</i>)-(+)-Cocaine and the First Synthesis of Cocaine C-1 Analogs from <i>N</i>-Sulfinyl β-Amino Ester Ketals,"Sulfinimine-derived α,β-unsaturated pyrrolidine nitrones, on heating with Al(O-t-Bu)(3), undergo a highly stereoselective intramolecular [3 + 2] cycloaddition to give tricyclic isoxazolidines, which are transformed in three-steps to give C-1 substituted cocaine analogs.",10.1021/ol1017118,2010-08-23,0.5979133403123358
Journal of Organic Chemistry,A Modular Approach for the Synthesis of Diverse Heterobifunctional Cyanine Dyes,"Herein, we present a straightforward synthetic route for the design and synthesis of diverse heterobifunctional cyanine 5 dyes. We optimized the workup by harnessing the pH- and functional group-dependent solubility of the asymmetric cyanine 5 dyes. Therefore, purification through chromatography is deferred until the last synthesis step. Demonstrating successful large-scale synthesis, our modular approach prevents functional group degradation by introducing them in the last synthesis step. These modifiable heterobifunctional dyes offer significant utility in advancing biological studies.",10.1021/acs.joc.3c02673,2024-02-27,0.5979120098530745
Synthesis,"Synthesis of (E,E,E)-(1,2,3,4-13C4)-Geranylgeraniol","All articles of this category A synthesis of ( E , E , E )-(1,2,3,4- 13 C 4 )-geranylgeraniol (2‘) (5 steps, ≥ 30% overall yield) is described starting from farnesol (3) . The synthesis is based on the Sum/Weiler protocol, which was found to be superior after investigating two different routes in the non-labelled series. geranylgeraniol - chain elongation - 13 C labelled compounds - (1,2,3,4- 13 C 4 )-ethyl acetoacetate - protein lipidation",10.1055/s-1997-1154,1997-02-01,0.5979117487197824
Angewandte Chemie International Edition,Enantioselective Total Synthesis of (−)‐Deoxoapodine,"The first enantioselective total synthesis of (-)-deoxoapodine is described. Our synthesis of this hexacyclic aspidosperma alkaloid includes an efficient molybdenum-catalyzed enantioselective ring-closing metathesis reaction for the desymmetrization of an advanced intermediate that introduces the C5-quaternary stereocenter. After C21-oxygenation, the pentacyclic core was accessed by electrophilic C19-amide activation and transannular spirocyclization. A biogenetically inspired dehydrative C6-etherification reaction proved highly effective to secure the F-ring and the fourth contiguous stereocenter of (-)-deoxoapodine with complete stereochemical control.",10.1002/anie.201708088,2017-09-01,0.5979105364548505
Tetrahedron,An efficient synthesis of the piperidinyl dihydroquinazolinone (PDQ) fragment of olcegepant,,10.1016/j.tetlet.2018.08.002,2018-08-02,0.5979067473273614
Synlett,Efficient Synthesis of the C1-C13 Fragment of Bistramide A,International audience,10.1055/s-0031-1290097,2011-12-09,0.5979067473273614
Organic Letters,An Advantageous Route to Oxcarbazepine (Trileptal) Based on Palladium-Catalyzed Arylations Free of Transmetallating Agents,"[reaction: see text] A new route to oxcarbazepine (Trileptal), the most widely prescribed antiepileptic drug, starting from commercially available 2'-aminoacetophenone and 1,2-dibromobenzene, is reported. The sequentially accomplished key steps are palladium-catalyzed intermolecular alpha-arylation of ketone enolates and intramolecular N-arylation reactions. After several experiments to establish the best conditions for both arylation processes, the target oxcarbazepine is obtained in a satisfactory overall yield, minimizing the number of steps and employing scalable catalytic procedures developed in partially aqueous media.",10.1021/ol051291p,2005-09-30,0.5979063623005691
Synthesis,Asymmetric Pauson-Khand Cyclizations of 1-Sulfinylenynes,"The use of sulfoxides as chiral auxiliaries in intramolecular Pauson-Khand (PK) reactions is described. In particular, the tert-butylsulfinyl group acts as a very efficient chiral auxiliary in intramolecular PK reactions of 1-sulfinyl-1,6-enynes. As the starting enynes are readily available in optically pure form and the final desulfinylation step is high yielding, this procedure constitutes an efficient alternative to the synthesis of enantiomerically pure bicyclo[3.3.0]oct-1-en-3-ones.",10.1055/s-2001-17511,2001-01-01,0.5979005695446418
Synthesis,"Palladium(II)-Catalyzed Sequential C−Cl Bond Formation: A Novel and Efficient Method for Direct α,α-Dichlorination of β-Dicarbonyl Compounds","A simple and concise procedure for the synthesis of 2,2-dichloro-3-oxo- N -phenylbutanamides, via palladium-catalyzed C(sp 3 )–H dichlorination of 3-oxo- N -phenylbutanamides, is described. The protocol provides a direct route to α,α-dichlorinated products starting from β-dicarbonyl compounds. A plausible mechanism for this transformation involving two consecutive chlorination steps is described.",10.1055/s-0033-1338515,2013-08-09,0.5978853246688016
Synthesis,"The First Total Synthesis of Racemic 3,4-Dihydroxy-2-(3-methylbut-2-enyl)-3,4-dihydronaphthalen-1(2H)-one","Racemic 3,4-dihydroxy-2-(3-methylbut-2-enyl)-3,4-dihydronaphthalen-1(2H)-one is synthesized for the first time, in seven steps, starting from commercially available α-tetralone. The key steps in this process are dihydroxylation using osmium tetroxide, benzylic oxidation mediated by sodium chlorite-tert-butyl hydro­peroxide, and prenylation.",10.1055/s-0029-1219761,2010-04-06,0.5978836687224747
Tetrahedron,Alternative synthesis of the chiral atypical β-adrenergicphenylethanolaminotetraline agonist SR58611A using enantioselective hydrogenation,,10.1016/s0040-4039(99)00807-2,1999-06-01,0.5978803745648786
Journal of Organic Chemistry,Synthesis of Phytuberin. 4-<i>endo-tet</i> Acid-Catalyzed Cyclization of α-Hydroxy Epoxides,"The total synthesis of phytuberin, a phytoalexin of the Solanum genus, from (-)-alpha-santonin is reported. The key steps include (a) reductive cleavage of the C-O bond of the gamma-lactone with concomitant protection of the C1 double bond, (b) Sharpless stereocontrolled hydroxy-assisted epoxidation of allylic alcohol 6 and simultaneous deprotection of the C1 double bond, (c) a rare 4-endo-tet acid-catalyzed cyclization of an alpha-hydroxy epoxide, and (d) an unprecedented 4-exo selenocyclization of a homoallylic alcohol.",10.1021/jo034129d,2003-05-01,0.5978795716251558
Journal of the American Chemical Society,Total Synthesis of the Actin-Depolymerizing Agent (−)-Mycalolide A:  Application of Chiral Silane-Based Bond Construction Methodology,"A highly convergent asymmetric synthesis of the actin-depolymerizing agent (−)-mycalolide A has been achieved through the assembly and union of the C1−C19 trisoxazole fragment 2 and the C20−C35 aliphatic fragment 3, respectively. The C1−C19 fragment 2 was constructed via a Kishi−Nozaki coupling between the C1−C6 subunit 4 and the C7−C19 subunit 5, which in turn was obtained from a highly stereoselective crotylation reaction of silane ( S )- 7 with trisoxazole aldehyde 8 . The synthesis of the C20−C35 fragment 3 has been accomplished using chiral silane-based bond construction methodology for the introduction of the stereochemical relationships. Union of the advanced intermediates 2 and 3 through a Schlosser−Wittig protocol, macrocyclization utilizing Yamaguchi conditions, and subsequent functional group adjustments completed the total synthesis of (−)-mycalolide A. The synthesis confirms the relative and absolute stereochemistry of (−)-mycalolide A, as well as illustrates the application of chiral silane-based C−C bond construction methodology to the asymmetric synthesis of complex molecules.",10.1021/ja002377a,2000-11-01,0.5978792130955582
Synthesis,Synthesis of HIV NNRTI Doravirine Analogues via Visible-Light Photoredox Decarboxylative Cross-Coupling,"A C(sp2)–C(sp3) decarboxylative cross-coupling reaction utilizing dual nickel and photoredox catalysis for rapid parallel synthesis of diverse C-ring analogues of the HIV NNRTI clinical candidate doravirine is developed and described herein. This protocol features an alkylation with readily available and inexpensive methyl bromoacetate followed by hydrolysis to prepare an advanced doravirine intermediate, which undergoes decarboxylative cross-coupling with a variety of aryl and heteroaryl bromides. The mildness, broad applicability, and sustainability of the current methodology are improvements over previously reported procedures and allow for rapid parallel synthesis of analogues. The optimization and scope of this method are reported.",10.1055/s-0037-1610155,2018-05-30,0.5978740093982866
European Journal of Organic Chemistry,Synthesis of Amino‐ and Hydroxymethyl Benzoxaboroles: Prominent Scaffolds for Further Functionalization,"Herein, we describe the development of a short, simple, and efficient synthesis of amino‐ and hydroxymethyl‐substituted benzoxaboroles. The key step in our strategy was the early stage incorporation of the boron by the borylation of an aniline. The formed boronates were then elaborated to the final products in two additional steps, usually in good yields. The synthetic sequence was amenable to be performed on a preparative scale and 4‐amino benzoxaborole 4b and 6‐hydroxymethyl benzoxaborole 10c have been prepared, without any significant decrease in the overall yield. The amino and hydroxymethyl present at the molecules are useful for further elaboration and/or conjugation to bioactive molecules and therefore we believe that this method should be useful in the development of new compounds for Medicinal Chemistry.",10.1002/ejoc.201900013,2019-02-13,0.5978725927939602
Organic Process Research & Development,"Process Research on [(2<i>S</i>)-(3-Fluorophenyl)-(1<i>S</i>)-(5-oxotetrahydrofuran- 2-yl)ethyl]carbamic Acid <i>tert</i>-Butyl Ester, a Lactone Intermediate for an Aspartyl Protease Inhibitor","Two processes for the preparation of lactone [2 S -(3-fluorophenyl)-1 S -(5-oxotetrahydrofuran-2-yl)ethyl]carbamic acid tert -butyl ester 1 starting from S -BOC-(3-fluorophenyl)alanine 3 are described. ( S )-(3-Fluorophenyl)alanine N -methyl- N -methoxy amide 10, the Weinreb amide of 3, was reacted with 2-(2-1,3-dioxanyl)ethylmagnesium bromide to provide key intermediate ketoacetal 11 . To achieve high yields for this conversion, the N−H of the BOC group in Weinreb amino acid amide 10 was deprotonated first with a simple Grignard reagent (methyl or benzylmagnesium halide) followed by Barbier reaction with magnesium metal and 2-(2-bromoethyl)-1,3-dioxane. The acetal group in 11 was opened oxidatively with ozone, and the resulting ester 15 was reduced selectively at low temperature with N -Selectride. Alternatively, the ketone moiety in 11 was reduced diastereoselectively with aluminum triisopropoxide in 2-propanol to give the undesired ( R, S )-diastereomeric alcohol. The alcohol was converted to the mesylate which was heated in solution to cause formation of oxazolidinone 19 through displacement of the mesylate group by the carbonyl moiety of the BOC group with loss of tert -butyl alcohol. This intramolecular reaction provided the desired ( S, S )-diastereomer. Finally, acetal 19 was converted to nitrile 20 with hydroxylamine hydrochloride in ethanol with catalytic toluenesulfonic acid at reflux. Basic aqueous hydrolysis of nitrile 20 followed by treatment with di- tert -butyl dicarbonate provided 1 . While the second process was longer, the inexpensive reagents, simple reaction conditions, and high yields made it the process of choice. Both processes have been run on a multikilogram scale.",10.1021/op030207n,2003-11-26,0.5978707184649429
Organic Letters,Total Synthesis of (±)-Mycothiazole and Formal Enantioselective Approach,"[Reaction: see text] A total synthesis of (+/-)-mycothiazole and a formal enantioselective approach have been achieved from 2,4-dibromothiazole. A chain extension of a homoallylic alcohol proceeding through an unsaturated sultone intermediate, generated by ring-closing metathesis, was used as a key step for the elaboration of the conjugated (Z)-dienol moiety.",10.1021/ol047603q,2004-12-30,0.5978644465717701
Chemical Science,Total synthesis of (−)-penicimutanin a and related congeners,The first total synthesis of penicimutanin A ( <bold>1</bold> ) was achieved within 10 steps (LLS).,10.1039/c9sc05252f,2019-11-20,0.5978633364124135
Organic Letters,Palladium-Catalyzed Synthesis of Conjugated Allenynes via Decarboxylative Coupling,"A new strategy to access conjugated allenynes via a decarboxylative coupling of propargyl esters of propiolates has been developed. In this process, allenyl-palladium intermediates are coupled with acetylides that are generated in situ to form the conjugated allenynes. Finally, the coupling is demonstrated to be highly stereospecific, providing a route to enantioenriched allenes.",10.1021/acs.orglett.7b01751,2017-09-29,0.5978616995482235
Synthesis,Syntheses of Phenothiazinylboronic Acid Derivatives - Suitable Starting Points for the Construction of Redox Active Materials,"Phenothiazinylboronic acid derivatives 3,7 and 9, useful building blocks for the construction of oligophenothiazines, are readily synthesized in good yield from brominated phenothiazines 5 and 6 by bromine-lithium exchange followed by trapping with trialkylborate (route A) or by palladium-catalyzed borylation with tetramethyl dioxoborolane (8) (route B). The novel class of tetrakis(phenothiazinylphenyl)methanes 11, showing remarkably large Stokes shifts and a reversible low oxidation potential, can be prepared in good yield by Suzuki coupling of tetrakis(p-bromophenyl)methane (10) with 3a.",10.1055/s-2002-32527,2002-06-28,0.5978551268518151
European Journal of Organic Chemistry,New Luminescent Materials Based on a Steroid Molecule,"An efficient way to synthesize new steroid derivatives substituted in the A ring is described; based on a new route to stable diazo steroid 3-diazoandrosta-1,4-dien-17-one (4). Using the Barton−Kellogg olefination, it is possible to combine the steroid molecule with a heterocyclic substructure: the oxazoline ring system. Unlike the starting material, the resulting oxazinylidene products 2 are luminescence dyes with high quantum yields, and possess Stokes shifts of about 100 nm. The described synthetic method opens the way for the development of new diagnostic and pharmaceutical materials containing a steroidal substructure.",10.1002/1099-0690(200009)2000:17<3001::aid-ejoc3001>3.0.co;2-d,2000-09-01,0.5978547129452012
Synlett,"A Facile Route to the Synthesis of Novel 2-Amino-1,4,5,6-tetrahydropyrimidines from Baylis-Hillman Products of Acrylonitrile","A facile route for the synthesis of novel 5-substituted-2-amino-1,4,5,6-tetrahydro pyrimidines from the Baylis-Hillman ­adducts obtained from reaction of aldehydes and acrylonitrile is ­described.",10.1055/s-2005-863728,2005-01-01,0.597852658327987
Synlett,Enantioselective Synthesis of the Sporolide Quinone Acid Fragment,"The sporolide quinone acid is a key fragment in the biosynthesis of the complex heptacyclic marine metabolite sporolide. We report a concise enantioselective route to this fragment, which is obtained in seven steps with 65% overall yield from trimethoxybenzene. The enantioselective transfer reduction is achieved by Ipc2BCl, and the absolute configuration of the product secured by X-ray analysis of its cinchonine salt. The target fragment is then obtained by methylation and oxidation to the quinone by AgO.",10.1055/s-0029-1217963,2009-09-09,0.5978443574169209
Organic Letters,Synthesis of Illudinine from Dimedone,"A total synthesis of the illudalane sesquiterpene illudinine was realized in eight steps and 14% overall yield from commercially available dimedone. The approach features tandem fragmentation/Knoevenagel-type condensation and microwave-assisted oxidative cycloisomerization to establish the isoquinoline core. Completion of the synthesis involves a recently reported cascade S N Ar/Lossen rearrangement on a densely functionalized aryl bromide and an optimized procedure for O -methylation of 8-hydroxyisoquinolines. The oxidative cycloisomerization proceeds by way of a novel inverse-demand intramolecular dehydro-Diels–Alder cycloaddition, which has a potentially broader appeal for preparing substituted isoquinolines.",10.1021/acs.orglett.6b03887,2017-01-30,0.5978348285748161
Journal of the American Chemical Society,Convergent Total Synthesis of Hikizimycin Enabled by Intermolecular Radical Addition to Aldehyde,"Hikizimycin ( 1 ), which exhibits powerful anthelmintic activity, has the most densely functionalized structure among nucleoside antibiotics. A central 4-amino-4-deoxyundecose of 1 possesses 10 contiguous stereocenters on a C1–C11 linear chain and is decorated with a cytosine base at C1 and a 3-amino-3-deoxyglucose at C6-OH. These distinctive structural features of 1 make it an extremely challenging target for de novo construction. Herein, we report a convergent total synthesis of 1 from four known components: 3-azide-3-deoxyglucose derivative 4, bis-TMS-cytosine 5, d -mannose 9, and d -galactose derivative 10 . We first designed and devised a novel radical coupling reaction between multiply hydroxylated aldehydes and α-alkoxyacyl tellurides. The generality and efficiency of this process was demonstrated by the coupling of 7c and 8, which were readily accessible from two hexoses, 9 and 10, respectively. Et 3 B and O 2 rapidly induced decarbonylative radical formation from α-alkoxyacyl telluride 8, and intermolecular addition of the generated α-alkoxy radical to aldehyde 7c yielded 4-amino-4-deoxyundecose 6-α with installation of the desired C5,6-stereocenters. Subsequent attachments of the cytosine with 5 and of the 3-azide-3-deoxyglucose with 4 were realized through selective activation of the C1-acetal and selective deprotection of the C6-hydroxy group. Finally, the 3 amino and 10 hydroxy groups were liberated in a single step to deliver the target 1 . Thus, the combination of the newly developed radical-coupling and protective-group strategies minimized the functional group manipulations and thereby enabled the synthesis of 1 from 10 in only 17 steps. The present total synthesis demonstrates the versatility of intermolecular radical addition to aldehyde for the first time and offers a new strategic design for multistep target-oriented syntheses of various nucleoside antibiotics and other bioactive natural products.",10.1021/jacs.0c06354,2020-07-06,0.5978233842502586
Tetrahedron,An efficient synthesis of dinaphthothiophene derivatives,,10.1016/j.tetlet.2008.05.045,2008-05-14,0.5978187787968587
Tetrahedron,Efficient synthesis of thiazoloquinazolinone derivatives,,10.1016/s0040-4039(03)01026-8,2003-05-19,0.5978187787968587
Synthesis,Efficient Synthesis of Polycyclic Pyridazine Derivatives,,10.1055/s-1982-29973,1982-01-01,0.5978187787968587
Tetrahedron,An efficient synthesis of 3-cyanoquinoline derivatives,,10.1016/s0040-4039(98)00677-7,1998-06-01,0.5978187787968587
Tetrahedron,Efficient synthesis of 3-oxygenated benzothiophene derivatives,,10.1016/j.tetlet.2007.01.141,2007-02-02,0.5978187787968587
Tetrahedron,"An efficient synthesis of 3,4-dioxocyclobutenecarboxylate derivatives",,10.1016/s0040-4039(00)97394-5,1990-01-01,0.5978187787968587
Tetrahedron,Efficient synthesis of unsaturated azido sugar derivatives,,10.1016/s0040-4039(01)96050-2,1973-01-01,0.5978187787968587
Tetrahedron,Alternative synthesis of cyclic IDP-carbocyclic ribose. Efficient cyclization of an 8-bromo-N1-[5-(phosphoryl)carbocyclic-ribosyl]inosine 5′-phenylthiophosphate derivative mediated by iodine,,10.1016/s0040-4039(99)00977-6,1999-07-01,0.5978084008521972
Journal of Organic Chemistry,"Stereoselective Synthesis of Spiropiperidines as BACE-1 Aspartyl Protease Inhibitors via Late Stage <i>N</i>-Arylation of a 1,8-Diazaspiro[4.5]dec-3-en-2-one Pharmacophore","A stereoselective synthesis of spiropiperidine compounds, exemplified by compound 1, was developed, which was based upon the late stage N-arylation of a 1,8-diazaspiro[4.5]dec-3-en-2-one pharmacophore. Previously, compound 1 was prepared in low overall yield from piperidinone 2 via the Strecker reaction. A new route was developed, which employed the stereospecific Corey-Link reaction of an enantiomerically pure trichloromethylcarbinol to give a template compound amenable to late stage N-arylation.",10.1021/jo400016m,2013-02-25,0.5977995870661088
Journal of Organic Chemistry,Stereoselective Transformations of (+)-Abietic Acid into (+)-Vitedoin B and (+)-Negundoin A,"The first synthesis of spirolactone (+)-vitedoin B (14 steps, 8.0% global yield) and spiro enol ether (+)-negundoin A (19 steps, 3.7% global yield), via a nor -labdane acetoxy ester, has been achieved starting from commercial (+)-abietic acid.",10.1021/jo5003533,2014-04-15,0.5977964914416934
Journal of Organic Chemistry,Semisynthesis of Chondroitin Sulfate E Tetrasaccharide from Hyaluronic Acid,"Chondroitin sulfate (CS) is crucial glycosaminoglycan that regulates key functions of the nervous system. CS-E is one of the key CS subtypes that modulates the biological function of CS. Herein, N-protecting-group-free semisynthesis of CS-E tetrasaccharide is reported using hyaluronic acid as a readily available starting material. The synthetic process utilizes the enzymatic degradation and selective C4 hydroxyl group conversion as key approaches for direct construction of the CS tetrasaccharide precursor, which furnishes the neuroactive CS-E tetrasaccharide in 15 steps.",10.1021/acs.joc.8b01987,2018-10-16,0.5977960965741622
Organic Letters,"A Facile Synthesis of <i>cis</i>-1-Methyl-1,2,3,3a,4,8b- hexahydropyrrolo[3,2-<i>f</i>]pyrindine, an Annulated Nicotine Analog","[reaction: see text] The title compound, 2, has been synthesized in 45% overall yield in six steps from 3-bromopyridine. The hexahydropyrrolo[3,2-f]pyrindine skeleton was constructed from key intermediate 5, via intramolecular azomethine ylide-alkene [3 + 2] cycloaddition. The present work constitutes a general method for rapid assembly of other related tricyclic nicotine analogues.",10.1021/ol026876n,2002-11-09,0.5977955363557866
Chemical Science,Total synthesis of crotophorbolone,"Convergent total synthesis of crotophorbolone was accomplished in 18 longest linear steps. Observation of unexpected thermodynamic stability of a <italic>cis,trans</italic> -5/7/6 tricycle would benefit synthetic design of tigliane- and daphnane-related diterpenoids.",10.1039/d0sc02829k,2020-01-01,0.5977879288691381
Organic Letters,The First Total Synthesis of (Corrected) Ritterazine M,Hecogenin acetate was converted to ritterazine M in 16 operations with an average yield per opearation of 87%. The overall linear yield was 12%. This confirmed 1 as the corrected structure for ritterazine M by total synthesis.,10.1021/ol016572l,2002-01-15,0.5977859155039995
Synlett,Synthesis of a ‘Propeller-Like’ Oligoheteroaryl with Alternating Pyridine and Oxazole Motifs,"The molecular architecture of oligomeric pyridyl-oxazole compounds is key to determining their mode of interaction with G-quadruplex DNA structures, which is a family of prominent anticancer biomolecular targets. We report herein an efficient synthetic route that begins with chelidamic acid and affords, in just seven steps, an unusual ‘propeller-like’ pyridyl-oxazole architecture with alternating pyridine and oxazole rings, that has not been yet validated as a G-quadruplex binder. The synthesis employs Van Leusen chemistry for the construction of oxazole rings from aldehydes, and two Pd(II)/Cu(I)-mediated cross-coupling reactions involving C–H activation of oxazoles for the formation of C–C bonds between bromopyridine intermediates and oxazole fragments. This modular synthesis was designed to be amenable to the construction of analogues.",10.1055/s-0034-1379549,2015-01-08,0.5977772152684658
Synthesis,"A Valuable Synthesis of Pyrrolo[1,2-<i>a</i>]quinoxalines, Indolo[1,2-<i>a</i>]quinoxalines and their Aza-Analogues by Palladium-Catalyzed Intramolecular Carbon-Nitrogen Bond Formation","A novel and efficient method for the construction of pyrrolo[1,2-a]quinoxalines, indolo[1,2-a]quinoxalines and their aza-analogues is described. The reaction involves a Pd-catalyzed intramolecular cyclization as the key step and provides the desired products in only two steps and good overall yields.",10.1055/s-2005-916033,2005-01-01,0.5977754564198878
Organic Letters,Enantioselective Synthesis of the Unsaturated Fragment of Callyspongiolide,"A synthesis of the unsaturated side chain of callyspongiolide has been accomplished from two chiral building blocks prepared by catalytic asymmetric procedures applied on simple starting materials. The synthesis of the chiral benzylic alcohol was based on an enantioselective aldol reaction of a substituted benzaldehyde catalyzed by a chiral amine, whereas the chiral homoallyl alcohol was prepared by the enantioselective crotylboration of iodomethacryl aldehyde catalyzed by a chiral phosphoric acid. Both fragments were joined together by using standard Sonogashira coupling conditions.",10.1021/acs.orglett.6b02897,2016-10-26,0.5977623396084084
Journal of Organic Chemistry,"First Syntheses of 2,2-Dimethyl-7-(2′-methylbut-3′-en-2′-yl)-<i>2H</i>-chromen-6-ol and 2-(3′-Methylbut-2′-enyl)-5-(2′-methylbut-3′-en-2′-yl)-1,4-benzoquinone, Novel Prenylated Quinone Derivatives from the New Zealand Brown Alga <i>Perithalia capillaris</i>","The first syntheses of 2,2-dimethyl-7-(2'-methylbut-3'-en-2'-yl)-2H-chromen-6-ol (1) and 2-(3'-methylbut-2'-enyl)-5-(2'-methylbut-3'-en-2'-yl)-1,4-benzoquinone (2), novel prenylated quinone derivatives from the New Zealand brown alga Perithalia capillaris, are reported, in which the key steps are consecutive Claisen rearrangements that proceed with both high chemo- and regioselectivity.",10.1021/jo801057x,2008-08-06,0.5977596715393674
Synthesis,New Method for the Synthesis of Sulforaphane and Related Isothiocyanates,"The biologically important isothiocyanate sulforaphane (4-isothiocyanatobutyl methyl sulfoxide) was synthesized in six simple steps from commercially available 4-aminobutan-1-ol with an overall yield of 64%. The new synthetic method is suitable for multigram-scale preparation of sulforaphane and does not require expensive or toxic reagents. A novel one-pot procedure was also developed for preparing isothiocyanates through reaction of amines with O-phenyl chlorothioformate under mild conditions. Additionally, methyl pyrrolidine-1-carbodithioate was obtained as an unexpected byproduct, and this protocol was shown to be useful for the synthesis of S-aryl or S-heterocyclic thiocarbamates with cyclic side chains.",10.1055/s-0031-1289601,2011-11-11,0.5977532675597012
Synthesis,"Improved Total Synthesis of 1,3,6-Trigalloyl-β-d-glucose from Glucose","Abstract A total synthesis of the naturally occurring 1,3,6-trigalloyl-β-d-glucose is reported. The highlights of the synthesis include a regioselective benzylation of levoglucosan, followed by a 1,6-ring opening via acetolysis. Galloyl substituents were introduced via esterification, and the mixture of anomers obtained could be fully converted into the targeted β-anomer via selective hydrazinolysis followed by activation of the anomeric position by a trichloroacetimidate of the 1′-anomeric hydroxyl group. 1,3,6-Trigalloyl-β-d-glucose and its synthetic α-anomer were obtained in an overall yield of 31% and 22%, respectively, from levoglucosan or in an overall yield of 37% of the β-isomer exclusively by recycling the α-isomer.",10.1055/s-0042-1752404,2023-02-27,0.5977519210505782
Synthesis,"Enantioselective Total Synthesis of Eudesma-3,11(13)-dien-12-oic Acid","The first enantioselective total synthesis of eudesma-3,11(13)-dien-12-oic acid 1 was achieved starting from (+)-dihydrocarvone in ten steps.",10.1055/s-2001-15218,2001-01-01,0.5977393368897843
Journal of the American Chemical Society,A Convergent Total Synthesis of (+)-Ineleganolide,"We report the total synthesis of the furanobutenolide-derived diterpenoid (+)-ineleganolide. The synthetic approach relies on a convergent strategy based on the coupling of two enantioenriched fragments, which are derived from (−)-linalool and (+)-norcarvone, respectively. A high-yielding, one-step Michael addition and aldol cascade furnishes a pentacyclic framework as a single diastereomer, thereby overcoming previous challenges in controlling stereochemistry. The endgame features an O 2 -facilitated C–H oxidation and a samarium diiodide-induced semipinacol rearrangement to furnish the highly rigid central seven-membered ring.",10.1021/jacs.3c02142,2023-03-29,0.5977273895225175
Synlett,Enantioselective Synthesis of an Advanced Intermediate for the Synthesis of Brefeldin A and Analogues,International audience,10.1055/s-2008-1032041,2008-02-01,0.597725581950856
Tetrahedron,Intramolecular reductive cyclization of an enone–aldehyde: a new approach to the synthesis of (±)-majusculone,,10.1016/j.tetlet.2013.01.087,2013-02-01,0.5977217323121216
Organic Letters,A Short and Efficient Route to Novel Scyphostatin Analogues,"[structure: see text]. Several novel scyphostatin analogues have been prepared in up to 18% yield over five steps from commercially available 4-bromoguaiacol, utilizing an organometallic addition to afford the desired syn-hydroxy-epoxides.",10.1021/ol0164132,2001-09-26,0.5977180377659466
Tetrahedron,Concise and efficient synthesis of 3′-O-triphosphates of 2′-deoxyadenosine and 2′-deoxycytidine,,10.1016/j.tetlet.2014.01.077,2014-01-25,0.5977054098098457
Tetrahedron,An efficient and concise synthesis of Indiacen A and Indiacen B,,10.1016/j.tetlet.2017.03.002,2017-03-02,0.5977054098098457
Tetrahedron,"An efficient and concise entry to (-)-4,5-dihydroxy----norvaline. Formal synthesis of clavalanine.",,10.1016/0040-4039(91)85018-z,1991-04-01,0.5977054098098457
Tetrahedron,A concise and efficient synthesis of vildagliptin,,10.1016/j.tetlet.2017.07.062,2017-07-18,0.5977054098098457
Journal of Organic Chemistry,A Novel Crystallization-Induced Diastereomeric Transformation Based on a Reversible Carbon−Sulfur Bond Formation. Application to the Synthesis of a γ-Secretase Inhibitor,"This paper describes a remarkably efficient process for the preparation of gamma-secretase inhibitor 1. The target is synthesized in only five steps with an overall yield of 58%. The key operation is a highly selective and practical, crystallization-driven transformation for the conversion of a mixture of tertiary benzylic alcohols into the desired sulfide diastereomer with 94:6 dr. This unprecedented process is based upon a reversible carbon-sulfur bond formation under acidic conditions.",10.1021/jo0705925,2007-05-24,0.5977025406170587
Journal of Organic Chemistry,Synthesis of the Cytotoxic Sponge Metabolite Haliclamine A,"A new convergent and unified synthesis of the marine natural alkaloid haliclamine A is described. The synthesis of 3-alkylpyridine monomers 8 and 9 was first achieved from a common thiophene intermediate 5. These syntheses make use of thiophene chemistry and the ability of cyclopropylcarbinols 20 and 21 to rearrange to the homoallylic bromides 22 and 23, respectively. The Zincke procedure for the synthesis of pyridinium salts was then applied to the corresponding amino derivatives 8 and 9 to give efficiently unsymmetrical bis-pyridinium macrocycle 1, whose reduction afforded haliclamine A.",10.1021/jo025650v,2002-08-15,0.5977011766048441
Journal of Organic Chemistry,"New Strategies for the Synthesis of Biologically Important Tetrapyrroles. The “B,C + D + A” Approach to Linear Tetrapyrroles","Linear tetrapyrroles related to phytochrome (1) were prepared in enantiospecific fashion by a new strategy beginning with ring-B,C synthons of type 19 (bis-iododipyrrins). Rings A and D were elaborated by Pd(0)-mediated coupling of 19a with the appropriate alkyne acid or amide derivatives 9 and 20, followed by intramolecular cyclization (method C: BC + D + A --> ABCD).",10.1021/jo991503u,1999-12-09,0.5976964154006003
Organic Letters,Total Synthesis of Wasabidienones B<sub>1</sub> and B<sub>0</sub> via SIBX-Mediated Hydroxylative Phenol Dearomatization,"The first total synthesis of the natural nondimerizing o-quinol (+)-wasabidienone B1 was achieved from commercially available 1,3,5-trimethoxybenzene. The key dearomatizing transformation was efficiently accomplished via a hydroxylative phenol dearomatization reaction using the stabilized lambda(5)-iodane reagent IBX (SIBX). (+)-Wasabidienone B1 was then converted into its congener (-)-wasabidienone B0 via an improved thermally induced ring-contracting isomerization reaction.",10.1021/ol802183p,2008-10-22,0.5976959002332014
Journal of Organic Chemistry,Convergent Synthesis of Polyhalogenated Quinoline <i>C-</i>Nucleosides as Potential Antiviral Agents,"2,5,6-Trichloro-1-(beta-d-ribofuranosyl)benzimidazole (TCRB) and 2-bromo-5,6-dichloro-1-(beta-d-ribofuranosyl)benzimidazole (BDCRB) are benzimidazole nucleosides that exhibit strong and selective anti-HCMV activity. We proposed to synthesize 2-halo-6,7-dichloro-4-(beta-d-ribofuranosyl)quinolines as 6 + 6 bicyclic analogues of TCRB. The synthesis used Wittig reactions in two key steps. The first Wittig reaction coupled a fully functionalized benzene with a ribofuranose derivative to provide (Z)-6-O-(tert-butyldimethylsilyl)-1-(4,5-dichloro-2-nitrophenyl)-1,2-dideoxy-3,4-O-isopropylidene-d-allo-1-enitol (5) as the basic skeleton for the target compounds. The following electrophile-mediated intramolecular cyclization of the cis-alkene (5) was found to afford (1S,2S)-2,5-anhydro-1-bromo-6-O-(tert-butyldimethylsilyl)-1-deoxy-1-(4,5-dichloro-2-nitrophenyl)-3,4-O-isopropylidene-d-allitol (8) as the major product. This alpha-stereoselectivity was contrary to the literature precedence. A double-bond isomerization was established to be the cause of the unexpected stereochemistry. The bromo group of 8 was displaced by a hydroxyl group. Oxidation of the hydroxy group and the reduction of a phenylnitro group provided (2S)-1-(2-amino-4,5-dichlorophenyl)-2,5-anhydro-6-O-(tert-butyldimethylsilyl)-3,4-O-isopropylidene-d-allose (11), which was subjected to the second Wittig reaction with a phosphacumulene to construct 4-[5-O-(tert-butyldimethylsilyl)-2,3-O-isopropylidene-alpha-d-ribofuranosyl]-6,7-dichloroquinolin-2-one (13). Halogenation followed by deprotection of 13 and led to the synthesis of 4-(alpha-d-ribofuranosyl)-2,6,7-trichloroquinoline (17) as the major product. The 2-aminophenone alpha-nucleoside (11) was successfully anomerized to the beta-anomer (19), which led to the synthesis of the targeted 2-chloro- and 2-bromo-6,7-dichloro-4-(beta-d-ribofuranosyl)quinolines (18and 21, respectively).",10.1021/jo020643s,2003-05-01,0.5976795739158319
Tetrahedron,"Stereocontrolled synthesis of (E,E,E)-chlorotrienes: Efficient intermediates for the construction of all E conjugated polyenes",,10.1016/s0040-4039(97)01156-8,1997-07-01,0.5976791689518942
Tetrahedron,"Asymmetric induction in the 1,7 ring closure of diene-conjugated diazo-compounds: a route to chiral 1h-2,3-benzodiazepines",,10.1016/s0040-4039(00)82347-3,1988-01-01,0.5976672411025564
Organic Letters,"Computer-Guided Design, Synthesis, and Protein Kinase C Affinity of a New Salicylate-Based Class of Bryostatin Analogs","Bryostatin 1 is in clinical trials for the treatment of cancer and Alzheimer's disease and is a candidate for a first-in-class approach to HIV/AIDS eradication. It is neither readily available nor optimally suited for clinical use. Using a function oriented synthesis strategy, a new class of bryostatin-inspired analogs was designed with a simplified salicylate-derived subunit, enabling step-economical synthesis (23 total steps) of agents exhibiting bryostatin-like affinity to protein kinase C (PKC).",10.1021/ol502491f,2014-09-19,0.5976617741577404
Tetrahedron,A novel diastereoselective synthesis of the lactone moiety of compactin,,10.1016/s0040-4039(01)81198-9,1984-01-01,0.5976603553902234
Organic Process Research & Development,"Development of a Total Telescoped Synthesis of a Renin Inhibitor Containing 3,4,5-Substituted Piperidine with Sterically Hindered Amide Bonds","A telescoped synthesis for the manufacturing of a renin inhibitor containing 3,4,5-substituted piperidine with sterically hindered amide bonds via a five-step synthetic route is described. Highlights of this scalable synthesis include: (1) the byproduct-controlled amidation protocol using Ghosez’s reagent in the presence of a mild acid scavenger for the formation of the first sterically hindered amide bond; (2) the chemoselective hydrolysis of a sterically hindered ester; (3) an efficient amidation reaction employing a soluble carbodiimide leading to the second sterically hindered amide bond; (4) filtration of the fumarate salt of the final drug substance, being the only necessary isolation step throughout the total synthesis. Without the necessity of isolating any intermediates, this telescoped process conserved equipment usage, consumed less solvents, and minimized process waste generation, energy consumption, personnel exposure, and environmental impact. It furnished kilogram quantities of high-quality active pharmaceutical ingredients.",10.1021/op500116w,2014-05-09,0.5976585205748052
Synlett,"A Facile Route to Tripyrrane from 2,5-Bis(hydroxymethyl)pyrrole and the Improved Synthesis of Porphine by the ""3 + 1"" Approach",,10.1055/s-1999-2565,1999-01-01,0.5976554280651524
Tetrahedron,Regio- and stereo-selective alkylation of 3-trimethylsilylmethyl dienolates. A novel synthesis of 3-alkylated 2-methallylsilanes,,10.1016/s0040-4039(01)90413-7,1981-01-01,0.5976535985574641
Tetrahedron,Efficient and selective synthesis of alkoxy substituted di(pyridin-2-yl)amines and N-arylpyridin-2-ylamines,,10.1016/j.tetlet.2012.01.084,2012-01-30,0.5976519773217989
Organic Process Research & Development,Development of a Robust Protocol for the Synthesis of 6-Hydroxybenzofuran-3-carboxylic Acid,"Benzofuran scaffolds are fundamental moieties found in a variety of biologically active natural products and synthetic drugs. In the course of one of our development programs, we needed to develop a practical and cost-effective manufacturing approach to such a benzofuran scaffold. Here we report a highly robust four-step, one-pot process that provides access to a 6-hydroxybenzofuran-3-carboxylic acid structure. An 1 H NMR monitoring study allowed a better understanding of the overall sequence of events and the nature of the detected intermediates. After six steps, including the optimized tandem process, the desired hydroxylated benzofuran was obtained in 40% yield with a purity above 99%.",10.1021/acs.oprd.9b00546,2020-01-28,0.5976516717253987
Angewandte Chemie International Edition,Asymmetric Total Syntheses of the Akuammiline Alkaloids (−)‐Strictamine and (−)‐Rhazinoline,"Strictamine and rhazinoline are representative methanoquinolizidine-containing akuammiline alkaloids that possess different stereochemistry at the C16 position. A unified approach to the enantioselective total syntheses of these two molecules is described. The key steps in this synthesis include a photocatalytic intra/intermolecular type II radical cascade reaction, a Tsuji-Trost allylation, a palladium- or nickel-mediated cyclization, and a late-stage intramolecular N-alkylation reaction.",10.1002/anie.201901074,2019-02-18,0.5976465758082471
Journal of Organic Chemistry,"Total Synthesis of (±)-Crinane from 6,6-Dibromobicyclo[3.1.0]hexane Using a 5-<i>exo</i>-<i>trig</i> Radical Cyclization Reaction to Assemble the C3a-Arylated Perhydroindole Substructure","Crinane embodies the tetracyclic framework associated with some of the most common Amaryllidaceae alkaloids. It has now been prepared in 10 steps from 6,6-dibromobicyclo[3.1.0]hexane (2). The initial step involves the thermally induced electrocyclic ring opening of cyclopropane 3 and capture of the resulting π-allyl cation with benzylamine to give an allylic amine that is readily elaborated to the 3°-amine 10. This last compound was engaged in a 5- exo- trig free radical cyclization reaction to give the C3a-arylated perhydroindole 11. Compound 11 was then converted, over two steps, into (±)-crinane, the hydrochloride salt of which has been subjected to single-crystal X-ray analysis.",10.1021/acs.joc.8b01088,2018-05-24,0.5976465403122618
Synlett,"Synthesis of (1α,5α,6α)-6-Amino-3-azabicyclo[3.1.0]hexane, a Novel Achiral Diamine","All articles of this category Synthesis of (1α,5α,6α)-6-amino-3-azabicyclo[3.1.0]hexane is described. Ethyl diazoacetate cycloaddition to a pyrroline or maleimide derivative provides the azabicyclohexyl system; amine introduction is then effected using a modified Curtius rearrangement. 3-Azabicyclo[3.1.0]hexane - cyclopropanation - ethyl diazoacetate cycloaddition - diamine synthesis - trovafloxacin",10.1055/s-1996-5684,2000-12-31,0.5976447945426215
Tetrahedron,"Novel two-step, one-pot synthesis of primary acylureas",,10.1016/j.tetlet.2010.09.003,2010-09-13,0.5976436374541166
Chemical Science,Asymmetric total synthesis of (+)-xestoquinone and (+)-adociaquinones A and B,"-promoted photoenolization/Diels-Alder, dehydration, and aromatization reactions. This asymmetric strategy provides a scalable route to prepare target molecules and their derivatives for further biological studies.",10.1039/d0sc07089k,2021-01-01,0.5976426419570637
Journal of the American Chemical Society,Total Synthesis of the <i>Cephalotaxus</i> Norditerpenoids (±)-Cephanolides A–D,"Concise syntheses of the Cephalotaxus norditerpenoids cephanolides A–D (8–14 steps from commercial material) using a common late-stage synthetic intermediate are described. The success of our approach rested on an early decision to apply chemical network analysis to identify the strategic bonds that needed to be forged, as well as the efficient construction of the carbon framework through iterative Csp 2 –Csp 3 cross-coupling, followed by an intramolecular inverse-demand Diels–Alder cycloaddition. Strategic late-stage oxidations facilitated access to all congeners of the benzenoid cephanolides isolated to date.",10.1021/jacs.1c00293,2021-02-12,0.5976416893696935
Synthesis,Chiron Approaches to the Antitumor Natural Product Fuzanin D,"Fuzanin D, a pyridine-containing natural product, which exhibits cytotoxic activity against DLD-1 cells, is synthesized in a concise manner using l -arabinose or ethyl l -lactate as chiral pool substrates in nine steps (14.4% overall yield) and six steps (30.8% overall yield), respectively. The key steps involve Wittig olefination and olefin cross-­metathesis.",10.1055/s-0036-1588343,2016-11-18,0.5976396159126395
Organic Process Research & Development,Chlorination at the 8-Position of a Functionalized Quinolone and the Synthesis of Quinolone Antibiotic ABT-492,"The total synthesis of quinolone antibiotic ABT-492 has been achieved in 67% yield over nine steps from 2,4,5-trifluorobenzoic acid. The highlights of this synthesis include a novel chemoselective chlorination at the 8-position of a highly elaborated quinolone core. In addition, a Lewis acid promoted cyclization reaction to form the quinolone heterocycle was developed which was incorporated into a one-pot, three-step cyclization/coupling/protection sequence that proceeds in 93% yield.",10.1021/op0600557,2006-06-21,0.5976378474641153
Journal of Organic Chemistry,"Synthesis of a <i>C</i>-Glycoside Analogue of β-Galactosyl Ceramide, a Potential HIV-1 Entry Inhibitor","A β-C-galactosyl ceramide was synthesized in a stereoselective manner, employing a Sharpless AD reaction and olefin cross metathesis as key steps.",10.1021/jo402115w,2013-11-07,0.5976339708864663
Synlett,A Novel Synthesis of 5E-Isomer-Free Carboprost Methyl Ester,Abstract A macrocyclic lactone strategy for the synthesis of 5E-isomer-free carboprost methyl ester was developed for the first time. The macrocyclic lactone being free of 5E-isomer can be easily prepared from modified Corey lactone. The key intermediate could be used as a building scaffold to prepare carboprost methyl ester and other prostaglandins effectively.,10.1055/a-1951-1985,2022-09-27,0.5976165172871204
Tetrahedron,A novel one-step synthesis of γ-lactones from olefins and phenyliodonium(ethoxycarbonyl)nonafluorobutylsulfonylmethanide catalyzed by copper(II) triflate,,10.1016/0040-4039(95)00671-x,1995-06-01,0.5976146880878767
Journal of Organic Chemistry,Total Synthesis and Structure Confirmation of Leptofuranin D,"A convergent total synthesis of leptofuranin D is described. The linear polyketide C12-C24 segment was assembled through addition of a chiral allenylzinc reagent, derived from mesylate 12, to the chiral aldehyde 11. Directed hydrostannation of the adduct 13 followed by iodinolysis and Sonogashira coupling yielded the enyne 16, which was converted to the methyl-substituted enye 20, through hydrogenolysis of the derived bromide 19. Hydrostannation of the terminal alkyne converted 21 to 22, which was then treated with iodine to afford the vinyl iodide 23. The dihydropyranone precursor 40 was prepared by addition of allenystannane 29 to aldehyde 27. Partial hydrogenation of the derived propargylic alcohol then protection as the TBS ether afforded the (Z)-olefin 34. Further homologation was effected through Witttig condensation of aldehyde 36 with the ylide derived from phosphonium bromide 37. Selective deprotection of the primary TES ether of 38, followed by conversion of alcohol 39 to iodide 40, completed the synthesis of the C1-C11 segment. Suzuki coupling of boronate 41, prepared from iodide 40, with vinyl iodide 23 led to diene 42, with the complete carbon skeleton of leptofuranin D. The synthesis was completed by oxidation of the unprotected alcohol of 42, followed by global desilylation and exposure of the resulting tetrol to MnO(2).",10.1021/jo0348930,2003-08-23,0.5976146503633859
Organic Letters,"Enantioselective Access to Chiral 2-Substituted 2,3-Dihydrobenzo[1,4]dioxane Derivatives through Rh-Catalyzed Asymmetric Hydrogenation","Rh-catalyzed asymmetric hydrogenation of various benzo[ b][1,4]dioxine derivatives was successfully developed to prepare chiral 2-substituted 2,3-dihydrobenzo[1,4]dioxane derivatives using ZhaoPhos and N-methylation of ZhaoPhos ligands with high yields and excellent enantioselectivities (up to 99% yield, >99% enantiomeric excess (ee), turnover number (TON) = 24 000). Moreover, this asymmetric hydrogenation methodology, as the key step with up to 10 000 TON, was successfully applied to develop highly efficient synthetic routes for the construction of some important biologically active molecules, such as MKC-242, WB4101, BSF-190555, and ( R)-doxazosin·HCl.",10.1021/acs.orglett.8b01469,2018-07-03,0.5976108540586583
Journal of Organic Chemistry,A Noncarbohydrate Based Approach to Polyhydroxylated Pyrrolidizines:  Total Syntheses of the Natural Products Hyacinthacine A<sub>1</sub> and 1-Epiaustraline,"[reaction: see text] A flexible route to polyhydroxylated pyrrolizidine alkaloids is described, starting from commercially available N-Boc pyrrole and using a partial reduction as the key step. Tactics for varying the stereochemistry around the ring by choice of partial reduction conditions are discussed and methods for constructing the bicyclic ring system of the pyrrolizidine targets are examined. Intramolecular S(N)2 type displacement reactions were found to be an efficient way of forming the requisite bicyclo ring systems while iodine-promoted cyclizations proved unsuitable. A first synthesis of hyacinthacine A1 is described that also confirmed the structure of the natural product, and a short stereoselective synthesis of 1-epiaustraline is also discussed in detail.",10.1021/jo050977s,2005-08-10,0.5976088914911871
Organic Process Research & Development,Full Oxidation of an α-Arylated Isochromane: Development of a Two-Step Sequence as an Alternative to the Carcinogenic Jones Reagent and Application to the Manufacturing Process of Servier Phase II Clinical Candidate <b>S44819</b>,"An original two-step sequence allowing the full oxidation of an α-arylated isochromane is described. This method has been safely implemented to manufacture diketone 2 at the kg scale, a key intermediate in the manufacturing route of a phase II post stroke Servier clinical candidate S44819 . This second-generation synthesis showcased better safety, replicability, and sustainability compared to the first-generation synthesis using an excess amount of Jones reagent. Further functionalization of 2 by cyclodehydration and condensation with hydrazine is also demonstrated, allowing the manufacture of clinical candidate S44819 at the kg scale.",10.1021/acs.oprd.5c00193,2025-07-29,0.5976061257344362
Organic Process Research & Development,"Continuous Process Improvement in the Manufacture of Carfilzomib, Part 1: Process Understanding and Improvements in the Commercial Route to Prepare the Epoxyketone Warhead","Epoxyketone 4 is an isolated intermediate in the manufacturing route to the commercial proteasome inhibitor carfilzomib (Kyprolis). Commercial process development and optimization efforts toward the preparation of epoxyketone 4 highlighted several opportunities for process improvement. In this article, three case studies are presented that demonstrate how a detailed understanding of the reaction mechanism led to improvements that increased the overall robustness of the process. In the first case study, the mechanism of racemization of an α-chiral enone was investigated, resulting in the development of an improved aqueous workup procedure. Next, the stability of a bleach/pyridine mixture used for the step 3 epoxidation reaction was studied, leading to the identification of pyridine as a key raw material and improved reaction conditions and control strategy to meet the conversion target. Finally, oxidized butylated hydroxytoluene (oBHT) was identified as an impurity arising from the use of BHT-stabilized tetrahydrofuran in steps preceding the oxidation. The process understanding obtained from these investigations led to the implementation of process improvements that improved the robustness of the process. The development of a second-generation route to 4 is the subject of part 2 in this series (DOI: 10.1021/acs.oprd.0c00052).",10.1021/acs.oprd.0c00051,2020-04-02,0.5976029595181825
Synthesis,"Asymmetric Total Synthesis of Rugulactone, an α-Pyrone from Cryptocarya rugulosa","A total asymmetric synthesis of rugulactone, a naturally occuring alpha-pyrone isolated from Cryptocarya rugulosa, is reported. The synthesis involved a cross-metathesis coupling reaction to construct the internal E-olefin group, a Still-Gennari olefination to construct the Z-configured alpha,beta-unsaturated ester group, and a one-pot deprotection and intramolecular lactonization reaction. The stereochemistry at C5 was controlled by the use of a chiral pool.",10.1055/s-0029-1218836,2010-06-25,0.5976010721910361
Journal of Organic Chemistry,Synthesis of 4-Sulfenyl Isoxazoles through AlCl<sub>3</sub>-Mediated Electrophilic Cyclization and Sulfenylation of 2-Alkyn-1-one <i>O</i>-Methyloximes,"An efficient method for the synthesis of 4-sulfenyl isoxazoles has been developed via AlCl 3 -mediated electrophilic cyclization/sulfenylation of 2-alkyn-1-one O -methyloximes. Remarkably, N -arylsulfanylsuccinimides are employed as electrophiles for the construction of 4-arylsulfanyl isoxazoles, and 4-alkylsulfanyl isoxazoles are accessed with dialkyl disulfides as electrophiles.",10.1021/acs.joc.9b00256,2019-03-13,0.59759227015524
Organic Letters,"Novel Synthetic Approach Toward (±)-β-Cuparenone via Palladium-Catalyzed Tandem Heck Cyclization of 1-Bromo-5-methyl-1-aryl-hexa-1,5-dien-3-ol Derivatives","A novel and convenient synthetic route toward (+/-)-beta-cuparenone and many other sesquiterpene natural product precursors has been developed via palladium-catalyzed tandem Heck cyclization of 1-bromo-5-methyl-1-aryl-hexa-1,5-dien-3-ols. [reaction: see text].",10.1021/ol062418t,2006-12-29,0.5975887372565195
Synlett,Convenient Synthesis and Isolation of 1-Aminocyclopropane-1-carboxylic Acid (ACC) and N-Protected ACC Derivatives,"A convenient route to 1-aminocyclopropane-1-carboxyl­ic acid (1, ACC) and N-protected derivatives was developed. This route utilizes a bisalkylation of an O-benzyl glycine derived imine followed by global deprotection via hydrogenation. Direct isolation of ACC from a non-aqueous stream or efficient conversion to N-protected derivatives in a single flask is described.",10.1055/s-2004-834793,2004-10-20,0.5975869059067851
Journal of the American Chemical Society,Intramolecular Silicon-Assisted Cross-Coupling:  Total Synthesis of (+)-Brasilenyne,"The first, total synthesis of (+)-brasilenyne (1) has been achieved in 19 steps from l-(S)-malic acid. The key elements of this approach are a highly diastereoselective ring-opening of a 1,3-dioxolanone with bis(trimethylsilyl)acetylene) promoted by TiCl4 to set a propargylic stereocenter and the successful application of the sequential ring closing metathesis/silicon-assisted intramolecular cross-coupling reaction for construction of the oxonin core structure of 1.",10.1021/ja028936q,2002-11-27,0.5975826235799634
Angewandte Chemie International Edition,Asymmetric Total Syntheses of Kopsane Alkaloids via a PtCl<sub>2</sub>‐Catalyzed Intramolecular [3+2] Cycloaddition,"Abstract A concise and asymmetric total synthesis of five kopsane alkaloids that share a unique heptacyclic caged ring system was accomplished. The key transformation in the sequence involved a remarkable PtCl 2 ‐catalyzed intramolecular [3+2] cycloaddition, which allowed for the rapid assembly of pentacyclic carbon skeletons bearing 2,3‐quaternary functionalized indoline. Expeditious construction of diverse indoline scaffolds with excellent control of diastereoselectivity demonstrated the broad scope and versatility of this key transformation.",10.1002/anie.202005048,2020-04-24,0.5975807149464422
Tetrahedron,"Total synthesis of an anticancer agent, mucocin. 2. A novel approach to a γ-hydroxy butenolide derivative and completion of total synthesis",,10.1016/s0040-4039(98)02440-x,1999-01-01,0.5975800535232478
Tetrahedron,Non-phosgene route to unsymmetrical ureas from N-Cbz-α-amino acid amides,,10.1016/j.tetlet.2013.07.141,2013-08-02,0.5975731359132672
Organic Process Research & Development,"An Efficient, Direct Bis-ortho-chlorination of 4-(Difluoromethoxy)aniline and Its Application to the Synthesis of BMS-665053, a Potent and Selective Pyrazinone-Containing Corticotropin-Releasing Factor-1 Receptor Antagonist","An efficient scale-up synthesis of ( S )-5-chloro-1-(1-cyclopropylethyl)-3-(2,6-dichloro-4-(difluoromethoxy)phenylamino)-pyrazin-2(1 H )-one, 1 ( BMS-665053 ), is described. This new process features a one-step direct bis-ortho-chlorination of 4-(difluoromethoxy)aniline with HCl and H 2 O 2, and a palladium-catalyzed coupling of 2,6-dichloro-4-(difluoromethoxy)aniline 2 and ( S )-3,5-dichloro-1-(1-cyclopropylethyl)pyrazin-2(1 H )-one 3 . The process was applied to the preparation of batches of 1 for preclinical toxicology studies.",10.1021/op2003198,2011-12-16,0.597572101078759
Tetrahedron,"Asymmetric synthesis of anthracyclinones using chiral acetal: synthesis of a new chiral AB-synthon, ()-2-bromo-6-ethynyl-6-hydroxy-5, 6, 7, 8-tetrahydro-1, 4-naphthoquinone, and its application for ()-7-deoxydaunomycinone",,10.1016/s0040-4039(00)96820-5,1987-01-01,0.597567296974333
Synthesis,A New Route to<i>N</i>-Substituted-2-aminomethyl-1-Cyclanols,,10.1055/s-1981-29550,1981-01-01,0.5975635629943201
Journal of Organic Chemistry,"Asymmetric Synthesis of 2,4,5-Trisubstituted Piperidines from Sulfinimine-Derived δ-Amino β-Ketoesters. Formal Synthesis of Pseudodistomin B Triacetate","[reaction: see text] N-Sulfinyl delta-amino beta-ketoester enaminones, a new sulfinimine-derived chiral building block, undergoes, on hydrolysis in one pot, an intramolecular Michael addition followed by a retro-Michael-type elimination to give enantiopure 2,4,5-trisubstituted piperidines, a structural motif found in numerous biologically active alkaloids. This new chiral building block is readily prepared by treating N-sulfinyl delta-amino beta-ketoesters with dimethylformamide dimethyl acetal. This new protocol was illustrated with a concise formal asymmetric synthesis of marine alkaloid pseudodistomin B triacetate.",10.1021/jo050373o,2005-05-27,0.5975622629289867
Synthesis,Synthesis of a New Pyrrolopyridoindoleand Its Pyrrolopyridobenzimidazole Regioisomer,"The synthesis of a new pyrrolopyridoindole was carried out according to two different synthetic pathways. Thus, the preparation of this new tetracyclic pyrrolopyridoindole and its pyrrolopyridobenzimidazole regioisomer was achieved via thermolysis of a 1-(7-azaindolyl)benzotriazole intermediate.",10.1055/s-0028-1087804,2009-02-11,0.5975551205590272
Synthesis,"6-endo-dig Cycloisomerization of N-Propargyl Aminoquinoxalines: A New Route to 1,4,8-Triazaphenanthrenes","We report the preparation of novel 1,4,8-triazaphenanthrenes and show that the target compounds are efficiently obtained from the corresponding 6-aminoquinoxalines after N-propargylation followed by copper-catalyzed 6-endo-dig cycloisomerization and aromatization. The cyclization was found to be completely regioselective.",10.1055/s-0035-1562443,2016-07-07,0.5975516581736409
Journal of Organic Chemistry,"Enantioselective Chemoenzymatic Synthesis of <i>cis-</i> and <i>trans</i>-2,5-Disubstituted Morpholines","A versatile synthesis of enantiomerically pure cis- and trans-2,5-disubstituted morpholines is described. Hydroxynitrile lyase-mediated cyanide addition onto aldehydes provided cyanohydrins in virtually quantitative yield and excellent enantioselectivity. Subsequent formation of diastereomerically pure amino esters via a three-step, one-pot reduction-transimination-reduction sequence followed by reduction and simultaneous protection provided cyclization precursors. Finally, cyclization and SmI(2)-mediated reductive detosylation completed the synthesis of cis- and trans-2,5-disubstituted morpholines in good yields and excellent diastereoselectivities.",10.1021/jo1003295,2010-04-12,0.5975383522214176
Angewandte Chemie International Edition,Highly Diastereo‐ and Enantioselective Pd‐Catalyzed Spiroaminoalkylation: One‐Step Construction of Multifunctional Angular Polycyclic Amines,"Angular polycycles are ubiquitous in natural products with significant biological properties. However, the straightforward catalytic asymmetric synthesis of spirocyclic scaffolds with multiple stereogenic centers from readily available starting materials remains largely underdeveloped and a formidable challenge. Using the aminoalkyl cyclopalladated complex as the key intermediate, we report herein the first example of diastereo- and enantioselective multifunctional angular tetracyclic- and pentacyclic amines synthesis through palladium-catalyzed spiroaminoalkylation/allylic substitution reaction (up to 92% yield, up to 99% ee). The synthetic versatility of this methodology is underscored by the efficient synthesis of chiral phosphine ligands, which further demonstrates its robust utility in concisely constructing versatile chiral ligands.",10.1002/anie.202522191,2025-11-26,0.5975367938223369
Tetrahedron,Synthesis and binding character of ether-ester-ethyleneurea podands and macrocycles-synthetic nactin analogs,,10.1016/s0040-4039(00)74783-6,1992-12-01,0.5975229601199658
Organic Letters,Concise Total Synthesis of Albaflavenone Utilizing Sequential Intramolecular Aldol Condensation: Determination of Absolute Configuration,"The first total synthesis of albaflavenone, a novel antibiotic sesquiterpene, has been accomplished via the concise construction of its zizaene skeleton utilizing sequential intramolecular aldol condensation followed by chemo- and diastereoselective reduction of the conjugated carbon-carbon double bond. This synthetic work was completed in nine steps from 2-cyclopenten-1-one as a starting material without the use of protecting groups and with high stereocontrol. In addition, the absolute configuration of naturally occurring albaflavenone was determined to be 1R,2S and 8S.",10.1021/ol503202d,2014-12-03,0.597520326011464
Journal of the American Chemical Society,Strain-Release Rearrangement of <i>N</i>-Vinyl-2-Arylaziridines. Total Synthesis of the Anti-Leukemia Alkaloid (−)-Deoxyharringtonine,"Deoxyharringtonine (1) is among the most potent of the anti-leukemia alkaloids isolated from the Cephalotaxus genus. A convergent total synthesis of (-)-1 is reported, involving novel synthetic methods and strategies that include (1) the strain-release rearrangement of N-aryl-2-vinylaziridines for [3]benzazepine synthesis, (2) a vinylogous amide acylation-cycloaddition cascade for spiro-pyrrolidine construction, and (3) efficient acylation of the cephalotaxine core by alpha-(beta-lactone)carboxylic acid derivatives to access the biologically active cephalotaxus esters. These innovations should allow rapid access not only to other Cephalotaxus alkaloids but also to non-natural analogues of potential therapeutic utility.",10.1021/ja063304f,2006-07-20,0.5975133976801581
Tetrahedron,Novel synthesis of 1-aryl-1-trifluoromethylallenes,,10.1016/j.tetlet.2005.10.166,2005-11-21,0.5975103653487883
Organic Letters,"Enantioselective Decarboxylative Alkylation of β-Keto Acids to <i>ortho</i>-Quinone Methides as Reactive Intermediates: Asymmetric Synthesis of 2,4-Diaryl-1-benzopyrans","A novel and efficient asymmetric synthesis of 2,4-diaryl-1-benzopyrans via enantioselective decarboxylative alkylation of β-keto acids to o-QM intermediates, followed by sequential cyclization and dehydration, has been developed. The synthetically useful chiral 2,4-diaryl-1-benzopyran derivatives were obtained in moderate to high yields and high enantioselectivities through a one-pot, two-step sequence. This approach offers a facile way to prepare chiral 2,4-diaryl-1-benzopyran derivatives with a wide range of functional group tolerance.",10.1021/acs.orglett.8b00993,2018-05-01,0.5975027553612466
Angewandte Chemie International Edition,Synthesis of the Furanosteroidal Antibiotic Viridin,"A rhodium-catalyzed alkyne cyclotrimerization, domino electrocyclic reactions, and a hydroxy-directed dihydroxylation are key steps in an efficient synthesis of the bioactive furanosteroid viridin (1) from a simple acyclic triyne.",10.1002/anie.200353129,2004-03-30,0.5974976112871556
Organic Letters,Convergent Synthesis of Piperidines by the Union of Conjugated Alkynes with Imines: A Unique Regioselective Bond Construction for Heterocycle Synthesis,"A two-step process is described for the union of aromatic imines, conjugated alkynes, and aldehydes that results in a stereoselective synthesis of highly substituted piperidines. This synthetic process has been made possible by defining a unique regioselective functionalization of conjugated alkynes that establishes a suitably functionalized substrate for subsequent heterocycle-forming cationic annulation. Given the flexibility of the coupling process, heterocycles can be accessed through a process that establishes up to four stereogenic centers and four fused rings.",10.1021/ol902169k,2009-10-09,0.5974971173171164
Tetrahedron,"Total synthesis of new 1,5-bissubstituted myo-inositol derivatives. Synthesis of D-myo-inositol 1,5-bisphosphate, 3,5-bisphosphate and of rac. 1,5-Bissulphated and 1,5-bissulphamoylated isosteric analogues",,10.1016/s0040-4039(00)97206-x,1990-01-01,0.5974923792759927
Tetrahedron,A new method for the synthesis of 2′-substituted purine nucleosides total synthesis of an antibiotic 2′-amino-2′-deoxyguanosine,,10.1016/0040-4039(76)80149-9,1976-12-01,0.5974913638963345
Journal of Organic Chemistry,"Synthesis of (2<i>S</i>,3<i>R</i>,4<i>R</i>)-Dihydroxyisoleucine for Use in Amatoxin Synthesis",")-4,5-dihydroxy isoleucine (DHIle), an amino acid found in α-amanitin, which appears to be critical for toxicity. This synthetic route is transition metal-free and enables the production of significant quantities of DHIle with suitable protection for use in peptide synthesis. Its incorporation into a cytotoxic amatoxin analog is reported.",10.1021/acs.joc.4c01051,2024-08-21,0.5974893689266797
European Journal of Organic Chemistry,Atropo-Enantioselective Synthesis of the Natural Bicoumarin (+)-Isokotanin A via a Configurationally Stable Biaryl Lactone,"The atropo-enantioselective total synthesis of the axially chiral bicoumarin (+)-isokotanin A (1) is described. Key steps were the formation of a configurationally stable seven-membered biaryl lactone and its kinetic resolution by atroposelective ring cleavage. The previous assignment of the absolute configuration of (+)-isokotanin A (1) (and its synthetic precursors) was confirmed by quantum chemical CD calculations. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)",10.1002/1099-0690(200203)2002:6<1096::aid-ejoc1096>3.0.co;2-z,2002-03-01,0.5974856247615681
Organic Letters,Synthesis Using Ring Closure Metathesis and Effect on Nucleoside Transport of a (N)-Methanocarba <i>S</i>-(4-Nitrobenzyl)thioinosine Derivative,"[reaction: see text] A new synthetic route to ring-constrained (N)-methanocarba nucleosides and nucleotides is presented. Ring closure of a diene intermediate using Grubbs catalyst provides a new avenue for the preparation of the cyclopentenone derivative 6, which is a versatile intermediate for various carbocycles. The product was almost as potent an inhibitor of es-mediated nucleoside transport as the parent compound, inhibiting initial rates of uptake of uridine into cultured CCRF-CEM cells by 50% at approximately 30-50 nM.",10.1021/ol006999c,2001-01-30,0.5974841901732485
Synlett,"Synthesis of (±)-12-Fluorohuperzine A, a Novel Acetylcholinesterase Inhibitor","All articles of this category The synthesis of (±)-12-fluorohuperzine A ( 5 ) has been accomplished by a method featuring the regioselective formation of the allyl bromide 8 from the exo-olefin 7 ( 7→8 ), the masking of the allyl alcohol 16 in a form of the ethyl acrylate 19 ( 16→17→18→19 ), and the conversion of the allyl alcohol 21 to the allyl fluoride 5 ( 21→5 ) as key steps. Taking into account its racemic form, this analogue exhibits 20 times less potent anti-acetylcholinesterase activity than natural (-)-huperzine A ( 1 ). (-)-huperzine A - (±)-12-fluorohuperzine A - acetylcholinesterase inhibitor - allyl bromide formation - monofluorination",10.1055/s-1997-6142,1997-06-01,0.5974787515543638
Journal of Organic Chemistry,A Flexible Stereospecific Synthesis of Polyhydroxylated Pyrrolizidines from Commercially Available Pyranosides,"Nitrogen-containing sugar analogues, known as azasugars or iminosugars, such as polyhydroxylated piperdines, pyrrolidines, pyrrolizidines, and indolizidines, have the potential to become important therapeutic agents due to their ability to inhibit glycosidases. Synthetic pathways that are able to systematically produce a variety of these azasugars are eagerly sought after, since even minute structural or stereochemical changes often significantly alter the degree of inhibition. The synthesis of tetrahydroxylated pyrrolizidines 40 and 41 starting from methyl alpha-d-glucopyranoside is described and will be used as a template to develop syntheses of all the stereoisomers of polyhydroxylated pyrrolizidine 9 as well as other analogous bicyclic polyhydroxylated iminosugars. The key steps in this synthesis involve a one-pot conversion of a halopyranoside to a divinylamine by employing a simultaneous Zn reduction and reductive amination of the resulting aldehyde. After protection of the amine, a ring-closing metathesis results in a multifunctional eight-membered ring that then undergoes an internal S(N)2 cyclization to form an alkene-containing pyrrolizidine 33. Dihydroxylation of the alkene followed by hydrogenolysis of the benzyl protecting groups results in tetrahydroxylated pyrrolizidines 40 and 41.",10.1021/jo051792o,2006-01-17,0.5974784242726944
Journal of Organic Chemistry,One-Pot Enantioselective Synthesis of Functionalized Pyranocoumarins and 2-Amino-4<i>H</i>-chromenes: Discovery of a Type of Potent Antibacterial Agent,"Function-oriented design and synthesis of chiral small molecules with novel activity is a key goal in modern organic chemistry. As multiple antibiotic-resistant pathogens are emerging and causing serious diseases, the need for practical routes for the development of new types of antibacterial agents is very urgent. Herein, we present a highly efficient process for the synthesis of optically active pyranocoumarins and 2-amino-4H-chromenes through an organocatalytic Knoevenagel/Michael/cyclization sequence, and the preliminary biological studies of these new heterocyclic compounds revealed potent antibacterial activity. This study provides a novel strategy for further research and development of new types of antibacterial agents effective against human pathogens.",10.1021/jo202020m,2011-12-13,0.5974711757127663
Organic Letters,Ring Opening/C–N Cyclization of Activated Aziridines with Carbon Nucleophiles: Highly Diastereo- and Enantioselective Synthesis of Tetrahydroquinolines,A simple strategy for the synthesis of substituted tetrahydroquinolines through regio- and stereoselective ring opening of N-tosyl aziridines with carbon nucleophiles generated from 2-(bromoaryl)acetonitriles followed by palladium-catalyzed intramolecular C-N cyclization is reported in excellent yields (up to >99%) and stereoselectivity (ee and de up to >99%).,10.1021/ol2016077,2011-07-18,0.5974664332707165
Organic Letters,Asymmetric Synthesis of 3-Substituted Isoindolinones:  Application to the Total Synthesis of (+)-Lennoxamine,An anionic chiral auxiliary mediated asymmetric alkylation of carbamate 2 provides 3-substituted isoindolinones 4 in high ee. This methodology was used in the first asymmetric synthesis of (+)-lennoxamine.,10.1021/ol047824w,2004-12-15,0.5974521372523345
Organic Letters,Total Synthesis of TAK-Kinase Inhibitor LL-Z1640-2 via Consecutive Macrocyclization and Transannular Aromatization,"The biomimetic total synthesis of LL-Z1640-2 (3) is reported without the use of phenol protection. The aromatic unit was constructed via the transannular aromatization of macrocyclic triketo-ester 2, which in turn was synthesized by macrolactonization using an intramolecular trapping of a triketo-ketene derived from dioxinone 1.",10.1021/ol102468k,2010-11-10,0.5974501085099934
Angewandte Chemie International Edition,Enantioselective Total Synthesis of (+)‐Plumisclerin A,"Abstract The first and enantioselective total synthesis of (+)‐plumisclerin A, a novel unique complex cytotoxic marine diterpenoid, has been accomplished. Around the central cyclopentane anchorage, a sequential ring‐formation protocol was adopted to generate the characteristic tricycle[4.3.1.0 1,5 ]decane and trans ‐fused dihyrdopyran moiety. Scalable enantioselective La III ‐catalyzed Michael reaction, palladium(0)‐catalyzed carbonylation and SmI 2 ‐mediated radical conjugate addition were successfully applied in the synthesis, affording multiple grams of the complex and rigid B/C/D‐ring system having six continuous stereogenic centers and two all‐carbon quaternary centers. The trans ‐fused dihyrdopyran moiety with an exo side‐chain was furnished in final stage through sequential redox transformations from a lactone precursor, which overcome the largish steric strain of the dense multiring system. The reported total synthesis also confirms the absolute chemistries of natural (+)‐plumisclerin A.",10.1002/anie.201808517,2018-08-16,0.5974490772377756
Synthesis,A Facile Synthesis and Enzymatic Resolution of Naturally Occurring Remotely Functionalized Alkylmethylmaleic Anhydrides from<i>Aspergillus wentii</i>: Aspergillus Acids A-D,"The first synthesis of four new naturally occurring remotely functionalized secondary mould metabolite anhydrides 1a-d is described starting from N-p-tolyl citraconimide (5) in three to six steps and 20-65% overall yields. The condensation of triphen­ylphosphine-maleimide adduct 6 with aldehyde 4 furnished the exo-imide 7, which after isomerization, hydrolysis, and acylation gave aspergillus acid A (1a) in 54% overall yield in four steps. The condensation of adduct 6 with aldehyde 15 similarly afforded the desired imide 17 in two steps. The acid-catalyzed hydrolysis of imide 17 directly furnished aspergillus acid B (1b), exposing the latent methyl ketone present as the terminal acetylene. Sodium borohydride induced chemoselective reduction of aspergillus acid B (1b) gave aspergillus acid C (1c), which upon acetic anhydride induced acylation, furnished aspergillus acid D (1d). A facile Amano PS catalyzed acylation of aspergillus acid C (1c) gave, in good yield, the desired (+)-aspergillus acid C (1e) in 70% ee and (-)-aspergillus acid D (1f) in 72% ee. In the present enzymatic reaction, the anhydride moiety presumably plays a crucial role in the substrate recognition, binding, and resolution process.",10.1055/s-2006-926326,2006-01-01,0.5974420534578977
Tetrahedron,A Suzuki cross-coupling route to substituted aziridines,,10.1016/s0040-4039(01)01903-7,2001-12-01,0.5974419157193733
Organic Letters,Enantiospecific Total Synthesis of Macrolactone Sch 725674,"The enantiospecific total synthesis of 14-membered macrolactone Sch 725674 was accomplished from tartaric acid. Key reactions in the synthesis include the Ley's dithiaketalization of an alkynone derived from the bis-Weinreb amide of tartaric acid, Boord olefination, and ring-closing metathesis of an acrylate ester.",10.1021/ol5018678,2014-07-17,0.5974403798923349
Tetrahedron,Isoxazol-route zu cyano-semibullvalenen,,10.1016/s0040-4039(01)80875-3,1985-01-01,0.5974367283004822
Synthesis,Convenient Synthesis of Volatile<i>Streptomyces</i>Lactones,"A convenient three-step synthetic approach towards 3-alkyl-5-methyl-2[5H]furanones is described. The steps involved in the synthesis are domino primary alcohol oxidation-Wittig reaction, acid-catalysed lactonisation and isomerisation. This synthetic approach has been exploited to synthesise four Streptomyces lactones.",10.1055/s-2005-870025,2005-01-01,0.5974365682172327
Journal of Organic Chemistry,An Efficient Synthesis of Novel Carbocyclic Nucleosides with Use of Ring-Closing Metathesis from<scp>d</scp>-Lactose,"This paper describes an efficient synthetic route for various types of novel carbocyclic nucleosides. The required stereochemistry of the targeted nucleosides was successfully obtained with use of Grubbs cyclization and Trost allylic alkylation from the carbohydrate chiral template ""D-lactose"".",10.1021/jo0202536,2002-08-20,0.597434538280752
Tetrahedron,Synthetic studies of didemnins. II. Approaches to statine diastereomers,"A short and efficient route to (3S,4R)-statine has been developed in connection with synthetic studies toward didemnins A,B and C.",10.1016/s0040-4039(00)96222-1,1987-01-01,0.5974326686417232
Journal of Organic Chemistry,The Total Synthesis and Structural Revision of Stagonolide D,"The total synthesis of the putative structure of stagonolide D has been completed. The relative and absolute configuration of stagonolide D was established by synthesizing its optical antipode. The adopted strategy involves the construction of the central macrolide employing ring-closing metathesis (RCM), followed by selective protecting group manipulations and a final concomitant -OTBS deprotection and displacement of an -OMs placed next to it, resulting in the formation of the epoxide ring.",10.1021/jo202138g,2012-02-06,0.5974326163217445
Tetrahedron,Olefin addition to acetylated glycals. A new route to C-glycosides.,,10.1016/s0040-4039(01)91404-2,1984-01-01,0.5974256263922356
Tetrahedron,"Sulfonyl carbanions in synthesis. I. A novel route to α,β-unsaturated carbonyl compounds.",,10.1016/s0040-4039(00)72629-3,1975-01-01,0.5974067654309776
Synlett,"Preparation and Applications of 2-Iodo-5-lithiothiophene: Synthesis of 8, 11-Thioleukotriene B<sub>3</sub>","All articles of this category The title reagent, prepared by lithiation of 2-iodothiophene using lithium diisopropylamide, reacts with a range of electrophiles; the resulting 5-substituted 2-iodothiophenes undergo efficient Sonogashira alkyne coupling reactions, thereby providing an efficient route to 5-substituted 2-(1-alkynyl)-thiophenes and derivatives. Preliminary details of the scope of this sequence are described as is its application to the synthesis of 8,11-thioleukotriene B 3 lithium salt.",10.1055/s-1990-21240,1990-01-01,0.5973957253427221
Organic Process Research & Development,Chromatography as an Enabling Technology in Pharmaceutical Process Development:  Expedited Multikilogram Preparation of a Candidate HIV Protease Inhibitor,"Chromatography plays a vital role in supporting preclinical pharmaceutical development, whether in providing assays for purity determinations, preparative separation of small amounts of intermediates for route selection studies, or purification of bulk drug substances on multikilogram scale. All three approaches are illustrated in the recent development of a candidate HIV protease inhibitor in these laboratories. Chiral supercritical fluid chromatography (SFC) on the hundreds-of-milligrams scale afforded an enantiopure intermediate to facilitate early synthetic studies, HPLC on the tens-of-grams scale provided purified material for use in salt form investigations, and HPLC using a 30 cm column was used to purify 5.6 kg of a key intermediate to provide material for early preclinical evaluations.",10.1021/op0300443,2004-01-15,0.5973947228895109
Synlett,New Strategies for the Synthesis of Hexahydropyrroloindole Alkaloids Inspired by Biosynthetic Hypotheses,This account concerns synthetic studies of dimeric hexahydropyrroloindole alkaloids. 1 Introduction 2 A Biosynthetic Hypothesis for Calycanthaceous Alkaloids 3 Background 3.1 Prior Synthetic Studies of Calycanthaceous Alkaloids 3.2 Overman’s Enantioselective Syntheses of Chimonanthine 4 Our Work on the Syntheses of Hexahydropyrroloindole Alkaloids 4.1 Early Synthetic Studies of Chimonanthine 4.2 Development of a Cobalt(I)-Promoted Reductive Dimerization Strategy 4.3 New Directions and Our Biosynthetic Hypothesis for Dimeric Indole Alkaloids 5 Conclusion,10.1055/s-2008-1032060,2008-02-01,0.5973811252545653
European Journal of Organic Chemistry,Straightforward and Regioselective Access to Unsaturated α‐Benzyl Butyrolactones,The efficient preparation of various substituted α‐benzyl unsaturated butyrolactones is described. The palladium‐mediated C–C bond formation that uses α‐bromomethylbutenolide and boron derivatives as coupling partners accounts for the key step of this synthetic approach. Our strategy exclusively affords the endocyclic adduct and represents an alternative to Heck‐type reactions. The synthesis and characterization of two nostoclide analogues has also been reported.,10.1002/ejoc.201700895,2017-08-02,0.5973702633567509
Journal of Organic Chemistry,"Studies toward the Total Synthesis of Mumbaistatin, a Highly Potent Glucose-6-phosphate Translocase Inhibitor. Synthesis of a Mumbaistatin Analogue","A strategy for the total synthesis of the highly potent glucose-6-phosphate translocase inhibitor mumbaistatin (1) and structural analogues was elaborated. Such compounds represent a lead structure in the development of potential new drugs for the treatment of diabetes. To evaluate the general strategy, the close mumbaistatin analogue 10 was synthesized in a convergent manner. The anthraquinone building block 20 was efficiently prepared via aryne/phthalide annulation. After conversion of 20 into the corresponding 9,10-dimethoxyanthracene-1-carbaldehyde derivative (13), coupling with a lithiated arene (12) and subsequent multiple oxidation under Jones conditions yielded the mumbaistatin analogue 10. The preparation of the functionalized arene intermediates was achieved exploiting highly regioselective bromination and ortho-lithiation reactions.",10.1021/jo026232t,2002-12-01,0.5973702245255277
Tetrahedron,New scalable and eco-friendly synthesis of gingerols,,10.1016/j.tetlet.2012.03.092,2012-03-29,0.5973701093143647
Tetrahedron,Synthesis of enantiopure azetidines: a route to new β-amino alcohols,,10.1016/j.tetlet.2005.09.061,2005-09-30,0.5973680416752064
Synlett,"Total Synthesis of Amphilectane-Type Diterpenoid (±)-7-Isocyanoamphilecta-11(20),15-diene","The total synthesis of amphilectane-type diterpenoid ()-7-isocyanoamphilecta-11(20),15-diene, isolated from the tropical marine sponge Cymbastela hooperi, was achieved. The synthesis involves construction of a cis-decalin ring by an intramolecular ­Diels-Alder reaction and construction of an all-trans-perhydro­phenalene ring by an intramolecular Michael reaction as the key steps.",10.1055/s-0030-1259514,2011-01-27,0.5973665858160768
Organic Letters,Concise Synthesis of the Oxapentacyclic Core of Cortistatin A,"A concise synthetic approach for constructing the oxapentacyclic framework of cortistatin A is described. The synthesis features a furan-oxyallyl [4 + 3] cycloaddition and double-intramolecular aldol reactions. In addition, an interesting core structure was obtained in 11 steps from furan by using our method.",10.1021/ol102058f,2010-10-06,0.5973604343465401
Tetrahedron,Synthesis of polyamines and polyamine toxins. An improved alkylation procedure,,10.1016/j.tetlet.2004.08.139,2004-09-14,0.5973597021355606
Organic Letters,A Desymmetrization Approach toward Highly Oxygenated <i>cis</i>-Decalins,The cis-decalin core 2 of the antibiotic branimycin has been prepared by desymmetrization of diepoxynaphthalene 4. The key steps involve two successive S(N)' opening of the oxa-bridges. An improved procedure for the synthesis of 4 is also described.,10.1021/ol900834c,2009-06-09,0.5973537286459754
Tetrahedron,Addition of penicillin Grignards to glyoxals a synthesis of novel penam ketoalcohols,,10.1016/s0040-4039(00)96318-4,1987-01-01,0.5973525518470455
Synthesis,Synthesis of Peracylated Derivatives of l-Ribofuranose from d-Ribose and Their Use for the Preparation of <b>β</b>-<b>l</b>-Ribonucleosides,"A practical synthesis of peracylated derivatives of β-l-ribofuranose 13-15 from d-ribose was accomplished in 6 steps (total yield: 30-45%). Compound 13 was employed for the preparation of 1-(β-l-ribofuranosyl)thymine (16) and -cytosine (17), which are key intermediates for the preparation of the nucleoside derivatives with β-l-configuration. Simultaneous transformation of 17 into β-l-ddC (19) and β-l-3’dC (20) was studied.",10.1055/s-2002-19805,2002-07-26,0.5973499504823139
Synlett,Practical and Efficient Synthesis of <i>C</i><sub>2</sub> Symmetrical Diamines with Zn/Me<sub>3</sub>SiCl,All articles of this category C 2 symmetrical diamines are efficiently obtained by reductive coupling of imines with the couple Zn/Me 3 SiCl. This high yielding method is very practical and cheap for large scale preparation. diamines - reductive coupling - zinc - trimethylchlorosilane - C2 symmetry,10.1055/s-1998-1790,1998-08-01,0.5973469032148654
Tetrahedron,A unified and common intermediate strategy for the asymmetric total synthesis of 3-deoxy-neo-inositol and conduritol E,,10.1016/j.tetlet.2016.06.127,2016-06-30,0.5973448547705568
Organic Letters,Asymmetric Total Synthesis of (+)-Spiroapplanatumine G,"Spiroapplanatumine G ( 7 ) is a spiro-meroterpenoid characterized by an unusual 6/5/7 tricyclic spirobenzofuran-3-one core. The first enantioselective total synthesis of spiroapplanatumine G ( 7 ) is reported, featuring a key enantioselective Diels–Alder reaction between an aurone ester and a silyloxydiene to assemble the spirobenzofuranone core. This strategic Diels–Alder transformation advantageously establishes the two contiguous stereogenic centers in a single step. Subsequent cyclopropanation/FeCl 3 -mediated oxidative ring expansion affords the desired tricyclic framework.",10.1021/acs.orglett.5c03226,2025-09-05,0.5973353441814858
Tetrahedron,"A new strategy for the synthesis of spiro[4,5]decanes: A formal total synthesis of acorone",,10.1016/s0040-4039(99)00114-8,1999-03-01,0.5973303725543667
Organic Letters,Direct Access of the Chiral Quinolinyl Core of Cinchona Alkaloids via a Brønsted Acid and Chiral Amine Co-catalyzed Chemo- and Enantioselective α-Alkylation of Quinolinylmethanols with Enals,"A strategy for the facile construction of the chiral quinolinylmethanolic structure, a core featured in cinchona alkaloids, is reported. A new reactivity is harnessed by TfOH-promoted chemoselective activation of α-C-H over O-H bond in quinolinylmethanols. The new reactivity is successfully engineered with an iminium catalysis in a synergistic manner to create a powerful conjugate addition-cyclization cascade process for synthesis of chiral quinoline derived γ-butyrolactones in good yields and with good to excellent enantioselectivities. The method enables the first total synthesis of natural product broussonetine in three steps.",10.1021/acs.orglett.8b00118,2018-02-07,0.5973289955563711
Journal of Organic Chemistry,The Synthesis of 4-Deazaformycin A,"The preparation of 4-deazaformycin A has been achieved. The synthesis features the condensation of a suitably substituted, lithiated 4-picoline with 2,3,5-tri-O-benzyl-d-ribonolactone, dehydration of the resulting hemiacetal, and ionic hydrogenation, followed by manipulation of the protecting groups and subsequent ring closure with the formation of 7-amino-3-(beta-d-ribofuranosyl)pyrazolo[3,4-c]pyridine.",10.1021/jo026715x,2003-07-15,0.5973250423263697
Journal of Organic Chemistry,Synthesis and Inhibitory Assessment of ACE2 Inhibitors for SARS-CoV-2: An <i>In Silico</i> and <i>In Vitro</i> Study,"High Resolution Image Download MS PowerPoint Slide The angiotensin-converting enzyme 2 (ACE2) is pivotal as the cellular receptor for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the virus responsible for COVID-19. This study presents a novel synthetic route for four analogues of MLN-4760, a known inhibitor of ACE2, guided by in silico docking predictions. These synthetic advances enabled in vitro pIC 50 assays confirming the inhibitory potency of the synthesized analogues. Lastly, this route was applied to the synthesis of novel 18 F-labeled ACE2 inhibitors for PET imaging applications.",10.1021/acs.joc.5c00918,2025-07-21,0.5973216608343797
European Journal of Organic Chemistry,An Improved Stereocontrolled Access Route to Piperidine or Azepane β‐Amino Esters and Azabicyclic β‐ and γ‐Lactams; Synthesis of Novel Functionalized Azaheterocyles,"Abstract An improved, efficient synthesis of some functionalized saturated azaheterocycles has been accomplished by controlled functionalization of various readily available cyclic compounds containing ring C=C bond. The stereocontrolled synthetic concept was based on the oxidative ring cleavage of various unsaturated scaffolds across ozonolysis followed by ring closing with double reductive amination with primary alkylamines or fluorinated alkylamines. The protocol provided versatile azaheterocyclic derivatives with a piperidine or azepane framework.",10.1002/ejoc.202100540,2021-05-26,0.5973183049944146
Journal of Organic Chemistry,"Synthesis of Enantiomerically and Diastereomerically Pure 2(<i>S</i>)-Amino-6(<i>R</i>)-hydroxy-1,7-heptanedioic Acid Dimethyl Ester Hydrochloride from Cycloheptadiene","The complete carbon framework of enantiomerically and diastereomerically pure 2(S)-amino-6(R)-hydroxy-1,7-heptanedioic acid dimethyl ester hydrochloride was derived from cycloheptadiene in six steps utilizing an amino acid-derived acylnitroso Diels-Alder reaction as the key step. This versatile amino diester has been previously used to synthesize amino-differentiated diaminopimelic acid (DAP) and biologically active analogues. In addition, after formation of a novel aminoxy diketopiperazine, the newly formed carboxyl groups were differentiated by a novel transpeptidation of the amino acid that directed the stereochemistry of the initial cycloaddition.",10.1021/jo015544d,2001-06-13,0.5973179988948463
Journal of Organic Chemistry,Asymmetric Synthesis of the Protoberberine Alkaloid (<i>S</i>)-(−)-Xylopinine Using Enantiopure Sulfinimines,"A concise enantioselective synthesis of (S)-(-)-xylopinine (1) is described involving the addition of the laterally lithiated derivative of o-tolunitrile of 16 to enantiopure sulfinimine (+)-14. Treatment of the resulting cyano sulfinamide adduct (-)-17b with DIBAL-H accomplishes five operations in a single pot and furnishes the cyclic imine (+)-18 in good yield. Reduction and cyclization affords (S)-(-)-1. Alternatively basic hydrolysis of 17b,c gives isoquinolone 21 that is cyclized and reduced to give (S)-(-)-1.",10.1021/jo010988v,2002-01-29,0.5973114603837171
Angewandte Chemie International Edition,Total Synthesis of Peloruside A through Kinetic Lactonization and Relay Ring‐Closing Metathesis Cyclization Reactions,"The other side: A convergent total synthesis of peloruside A (1) is described. The key strategic features are a diastereoselective lactonization to generate a C5–C9 valerolactone from the C2-symmetric ketone 3, and a relay ring-closing metathesis reaction to produce a dehydrovalerolactone 2. A new isomer of 1, the valerolactone isopeloruside A (iso-1), was identified. MOM=methoxymethyl.",10.1002/anie.201002293,2010-07-19,0.5973088119266476
Tetrahedron,"Synthesis of melicodenines C, D and E","A synthesis of the unusual cyclobutane-quinolinone alkaloids melicodenines C, D and E by intermolecular [2+2] cycloaddition is described.",10.1016/j.tetlet.2012.10.087,2012-10-27,0.5973078010364447
Journal of Organic Chemistry,"New Asymmetric Approach to Natural Pyrrolizidines:  Synthesis of (+)-Amphorogynine A, (+)-Amphorogynine D, and (+)-Retronecine","Three natural pyrrolizidines, (+)-amphorogynines A and D and (+)-retronecine, have been prepared from a common lactam intermediate. This central compound, in turn, was synthesized in diastereomerically enriched form through a highly selective [2 + 2]-cycloaddition of dichloroketene with a chiral enol ether, followed by Beckmann ring expansion and reduction. Subsequent stereocenters were then cleanly introduced through internal induction.",10.1021/jo050983o,2005-09-21,0.5973030685861122
Synlett,A New Preparative Route to Substituted Dibenzofurans by Benzannulation Reaction. An Application to the Synthesis of Cannabifuran,"A new regioselective pathway to substituted dibenzo­furan derivatives is described here. According to this procedure substituted 1-acetoxy-3-alkoxycarbonyl dibenzofurans are obtained by treatment of 6-(2-methoxyaryl)-3-alkoxycarbonylhex-3-en-5-ynoic acids with acetic anhydride in the presence of sodium acetate. The latter acids are prepared from the easily available substituted o-iodo-anisoles by Sonogashira coupling with propargylic alcohol and Wittig reaction as the key steps. The described benzannulation reaction proceeds in regioselective fashion and a range of sub­stituents are tolerated. Its synthetic utility is demonstrated by a new synthesis of cannabifuran, a naturally occurring dibenzofuran.",10.1055/s-2003-42037,2003-01-01,0.5973025022607908
Angewandte Chemie International Edition,Enantioselective Synthesis of (−)‐Exiguolide by Iterative Stereoselective Dioxinone‐Directed Prins Cyclizations,Three become one: The title compound can be prepared in 26 steps by employing a unified Prins cyclization strategy to construct both tetrahydropyran rings (see scheme). The route combines two similar dioxinone fragments and one aldehyde component to generate the core structure. (−)-Exiguolide selectively inhibits the growth of A549 cancer cells at low concentrations; the triene side chain and the Z-enoate geometry are both necessary for this cytotoxicity.,10.1002/anie.201102790,2011-08-17,0.5972978956380771
Journal of the American Chemical Society,Total Synthesis of (−)-Himandrine,"We describe the first total synthesis of (-)-himandrine, a member of the class II galbulimima alkaloids. Noteworthy features of this chemistry include a diastereoselective Diels-Alder reaction in the rapid synthesis of the tricycle ABC-ring system in an enantiomerically enriched form, the use of a formal [3+3] annulation strategy to secure the CDE-ring system with complete diastereoselection, and successful implementation of our biogenetically inspired oxidative spirocyclization of an advanced intermediate. The successful and direct late-stage formation of the F-ring in the hexacyclic core of himandrine drew on the power of biogenetic considerations and fully utilized the inherent chemistry of a plausible biosynthetic intermediate.",10.1021/ja903790y,2009-06-25,0.5972869932071998
Organic Process Research & Development,New Ligand Development for Nickel-Catalyzed Reductive Cross-Coupling Enabling Practical Synthesis of SGLT-2 Inhibitors,"The mild and practical synthesis of SGLT-2 inhibitors (empagliflozin, dapagliflozin, and canagliflozin) has been achieved via nickel-catalyzed reductive cross-coupling, followed by deprotection. The ligand in this cross-coupling reaction is essential for both the reactivity and stereoselectivity. After conducting several rounds of the ligand “design–synthesis–test” sequence, a new ligand 4′-Bu-Terpy with a simple structure and low cost was discovered, affording the C -aryl β- d -glucoside products in high yields. The decagram-scale synthesis of empagliflozin, dapagliflozin, and canagliflozin through the glycosylation and hydrolysis procedure was also demonstrated, with the products isolated by the recrystallization method.",10.1021/acs.oprd.5c00302,2025-10-13,0.5972760425443123
Journal of Organic Chemistry,Asymmetric Synthesis of α-Chloro-β-amino-<i>N</i>-sulfinyl Imidates as Chiral Building Blocks,"New chiral α-chloro-β-amino-N-sulfinyl imidates were synthesized in high yield and excellent diastereomeric excess via highly anti-selective Mannich-type reactions of (R(S))-methyl N-tert-butanesulfinyl-2-chloroethanimidate with aromatic aldimines. The α-chloro-β-amino-N-sulfinylimidates proved to be excellent building blocks for the asymmetric synthesis of β-amino-α-chloro amides and esters, aziridine-2-carboxylic amides and esters, trans-2-aryl-3-chloroazetidines, and methyl 4-phenyloxazolidin-2-one-5-carboxylate. The obtained absolute anti-diastereoselectivity is the opposite of the stereochemical outcome observed for α-methyl-substituted imidates.",10.1021/jo200082w,2011-03-07,0.5972746784047281
Tetrahedron,A novel route to stereodefined cyclopropyl-substituted alkenes,,10.1016/s0040-4039(00)00490-1,2000-05-01,0.5972700013679981
Journal of Organic Chemistry,"Synthesis of Cyclo-2,2‘:4‘,4‘‘:2‘‘,2‘‘‘:4‘‘‘,4‘‘‘‘:2‘‘‘‘,2‘‘‘‘‘:4‘‘‘‘‘,4-sexipyridine","Preparation of the title compound (2) by use of Stille couplings and a Kröhnke pyridine synthesis is described. By application of the Stille coupling reaction, preparation and functionalization of quater- and quinquepyridines 26, 27, and 28 were achieved. Elaboration of quinquepyridine 27 to the pyridinium salt 30 bearing a protected enal allowed for the synthesis of 2 by a one-pot deprotection/Kröhnke reaction in nine steps from 4,4'-bipyridine. Use of the Kröhnke pyridine synthesis has been applied to prepare sexipyridine dibromide 19, but attempts to induce a macrocyclization via metal-mediated (Pd/Ni/Cu) aryl-aryl coupling procedures proved unsuccessful. Acetylene-bridged sexipyridines 3a and 3b incorporating 2,2'-bipyridine units proved to be inaccessible via sp-sp(2) or sp-sp coupling protocols.",10.1021/jo962236k,1997-05-01,0.597267494368388
Tetrahedron,A novel concise total synthesis of (+)-lentiginosine,,10.1016/s0040-4039(02)02606-0,2003-01-01,0.5972610263323695
Journal of the American Chemical Society,A Concise Total Synthesis of <scp>dl</scp>-Histrionicotoxin,"The synthesis of (+/-)-histrionicotoxin has been achieved in just nine steps using a two-directional synthesis strategy. Key reactions include a two-directional cross-metathesis, a tandem oxime formation/Michael addition/1,4-prototopic shift/[3 + 2]-cycloaddition cascade, a selective Z,Z-bisenyne formation, and a one-pot N-O and bischloroacetylene reduction.",10.1021/ja065015x,2006-09-12,0.5972581656807167
Journal of Organic Chemistry,"A Concise Formal Synthesis of Alkaloid Cryptotackiene and Substituted 6<i>H</i>-Indolo[2,3-<i>b</i>]quinolines","A five-step formal synthesis of alkaloid cryptotackiene and its 2-formyl, 11-methyl/phenyl derivatives involving conjugate addition of enolate anion from cyclohexanone (or 4-methylcyclohexanone) to bis[(methylsulfanyl)methylene]-2-oxindole followed by heterocyclization in the presence of ammonium acetate as the key step has been developed. The 11-methylsulfanyl group in the initial precursor can be either desulfurized (Raney Ni) or replaced by methyl/phenyl groups via nickel-catalyzed cross-coupling reaction with appropriate Grignard reagents.",10.1021/jo049227t,2004-07-16,0.5972561807092356
Angewandte Chemie International Edition,Expeditious Routes to Evernitrose and Vancosamine Derivatives and Synthesis of a Model Vancomycin Aryl Glycoside,Only seven steps are required to synthesize the activated derivatives 2 and 3 of evernitrose and vancosamine from the common intermediate 1 derived from L-lactic acid. The expeditious route to 3 was followed by its efficient incorporation into a vancomycin model system (4).,10.1002/(sici)1521-3773(19980803)37:13/14<1871::aid-anie1871>3.0.co;2-1,1998-08-03,0.5972534866424043
Tetrahedron,"Concise synthesis of a taxol A-ring synthon: Formation of a 1,2-alkylidene linkage via acetylene chemistry",,10.1016/s0040-4039(00)77146-2,1994-04-01,0.5972516243932102
Journal of Organic Chemistry,Enantiodivergent Synthesis of Both Enantiomers of Gypsy Moth Pheromone Disparlure,"Enantiodivergent synthesis of both (-)- and (+)-disparlure, a bioactive pheromone, possessing a cis-epoxide has been accomplished. The key step involves the cross metathesis of a chiral homoallylic alcohol derived from l-(+)-tartaric acid.",10.1021/jo070060o,2007-03-17,0.5972404621058873
Organic Letters,Formal Total Synthesis of (−)-Apicularen A via Transannular Conjugate Addition,"The formal total synthesis of the myxobacteria metabolite (-)-apicularen A (1) is described. The key step involved a novel acid-mediated transannular conjugate addition of the C13 hydroxyl into the alpha,beta-unsaturated ketone in either of the macrolactones 5a or 5b to provide the same trans-pyranone 4. Conversion of 4 into the known apicularen intermediate diol 3 completed the formal synthesis. [reaction: see text]",10.1021/ol0497943,2004-03-19,0.5972404205697749
Angewandte Chemie International Edition,Total Synthesis of Xerulinic Acid,"An inhibitor of the biosynthesis of cholesterol, xerulinic acid, has been synthesized for the first time. The convergent approach applied involves the palladium-catalyzed coupling of an enediynoic ester building block, a conjunctive C6 bisstannane, and a bromine-containing methylenebutenolide (see scheme; R=Me3SiCH2CH2).",10.1002/anie.200453729,2004-08-25,0.5972268813841299
Tetrahedron,"A syntethic route to 1,2,4,5-tetrahydro-3H-bez[e]indoles",,10.1016/s0040-4039(01)88345-3,1969-01-01,0.5972195807712648
Journal of Organic Chemistry,A Chemoenzymatic Total Synthesis of (+)-Clividine,"The title compound, ent-1, the non-natural enantiomeric form of the lycorenine-type alkaloid (-)-clividine (1), has been prepared using the enantiomerically pure (ee >99.8%) cis-1,2-dihydrocatechol 3 as starting material. A key feature associated with the closing stages of the synthesis involved the diastereoselective addition of a nitrogen-centered radical onto a pendant cyclohexene to establish the cis-fused D-ring and the required stereochemistry at C11b in the final product ent-1.",10.1021/jo201005d,2011-06-06,0.5972096396077637
Tetrahedron,A convergent mercury mediated lignan synthesis,,10.1016/s0040-4039(00)86892-6,1982-01-01,0.5972084042979969
European Journal of Organic Chemistry,The First Stereoselective Total Synthesis of (–)‐Synrotolide,"Abstract The first stereoselective total synthesis of (–)‐synrotolide has been realized by two different approaches, both starting from ( S )‐ethyl lactate. Both strategies used stereo‐ and regioselective epoxide opening with a nucleophile, aldehyde alkyne coupling and ring‐closing metathesis as key steps. Judicious choice of reagents (CeCl 3 · 7H 2 O and H 2 SiF 6 ) for the chemoselective removal of protecting groups delivered the target molecule.",10.1002/ejoc.201301215,2013-11-07,0.5972071602096451
Organic Letters,"Sequential Hydrozirconation/Cyclization of Dienes, a New Route toward <i>Trans</i> 2-Substituted Vinylcyclopentanes","The diastereoselective synthesis of trans-2-substituted vinylcyclopentanes is described. The method is based on the intramolecular coupling of 7-methoxy-1,5-dienes involving a sequential activation of the C═C double bonds via hydrozirconation and TMSOTf-promoted allylation.",10.1021/ol500400s,2014-02-26,0.5972067933014507
Synthesis,"Expedient Synthesis of 1,3-Cyclobutanedione via Thermal Dimerization of<i>t</i>-Butoxyethyne","All articles of this category A new, short, and efficient synthesis of 1,3-cyclobutandione consists of the therma conversion of t -butoxyethyne into 3- t -butoxycyclobutenone (the first example of cyclobutenone formation from an unsubstituted acetylenic monoether) followed by cleavage of the t -butyl group with trifluoroacetic acid. The 62% overall yield is much higher than that of the previously described procedure.",10.1055/s-1985-31444,1985-01-01,0.5972048910731995
Journal of the American Chemical Society,Enantioselective Total Synthesis of Bipolarolides A and B,"Bipolarolides A and B are members of the ophiobolin family of sesterterpenes, characterized by their intricate cage-like structures. Herein we report a concise asymmetric total synthesis of bipolarolides A and B enabled by the type-II Diels-Alder reaction. The synthesis features a sequence of key transformations: an iridium-catalyzed enantioselective allylation to establish the first stereocenter, type-II Diels-Alder reaction to rapidly assemble the bicyclo[3.3.1]non-1-ene core, reductive oxy-ring opening with olefin isomerization, aldol cyclization to construct a D ring, and a late-stage electrochemical C-H oxidation to complete the ether ring.",10.1021/jacs.5c09835,2025-07-25,0.597201395718455
Tetrahedron,"An efficient diastereoselective one-pot synthesis of dihydrofuro[2′,3′:2,3]indeno[2,1-b]furan derivatives",,10.1016/s0040-4039(02)00435-5,2002-04-01,0.5971976196079525
Journal of Organic Chemistry,Dihydropyrazinoquinazolinones via S<sub>N</sub>2 Sulfamidate Ring-Opening and a Sequential Quinazolinone–Amidine Rearrangement Strategy (SQuAReS),"]-quinazolinones is described using a 2-alkylaminoquinazolinone-mediated ring opening of a-/chiral sulfamidates, followed by a tandem quinazolinone-amidine rearrangement termed SQuAReS. This approach takes advantage of sulfamidates whose regioselective ring opening, after hydrolysis, appends an optimally distanced nucleophilic amine to a quinazolinone such that subsequent domino rearrangements are favored, integrating unique substitution patterns on a privileged core. This three-step protocol integrated five telescoped transformations and generated 20 pyrazinoquinazolinones in up to 74% yield with high enantiomeric fidelity and diastereoselectivity.",10.1021/acs.joc.2c01717,2022-10-04,0.5971961749428271
Journal of Organic Chemistry,Route to Functionalized Tetrahydrobenzo[<i>d</i>]azepines via Re<sub>2</sub>O<sub>7</sub>-Mediated Intramolecular Friedel–Crafts Reaction,"-mediated intramolecular dehydrative Friedel-Crafts reaction for the efficient synthesis of various benzo-fused heterocycles such as benzazepines and benzazocines. This process is characterized by a broad substrate scope, mild reaction conditions, high efficiency, and high atom economy. The potential application of this methodology was exemplified by the facile preparation of a NMDA antagonist as well as a key intermediate en route to SKF 38393.",10.1021/acs.joc.3c01977,2024-01-22,0.5971916063761039
Synthesis,Synthesis of Polycyclic Sultams by Palladium-Catalyzed Intramolecular Cyclization,"A practical and high-yielding method for the synthesis of new sultams from readily available sulfonamides, 1-naphthylamine, and 2-halobenzyl bromides is reported. A variety of tricyclic, tetracyclic, and pentacyclic sultams have been prepared via palladium-catalyzed, ligand-free intramolecular cyclization. Detailed mechanistic studies of the reaction pathway are also described.",10.1055/s-0029-1216888,2009-07-07,0.597188242850488
Journal of Organic Chemistry,A Convenient 3-Step Synthesis of (<i>R</i>)<i>-</i>7<i>-</i>Hydroxycarvone from (<i>S</i>)-α-Pinene,"A convenient 3-step synthesis of (R)-7-hydroxycarvone (2) has been developed starting from (S)-alpha-pinene (7), using photooxygenation, oxidation, and fragmentation reactions. An improved synthesis of epoxy alcohol 6 and an unusual Ti(OiPr)(4) catalyzed hydroxy epoxide to keto alcohol rearrangement are also described.",10.1021/jo050217h,2005-05-20,0.5971868411827137
Journal of Organic Chemistry,"General Approach to the Synthesis of the Chlorosulfolipids Danicalipin A, Mytilipin A, and Malhamensilipin A in Enantioenriched Form","A second-generation synthesis of three structurally related chlorosulfolipids has been developed. Key advances include highly stereocontrolled additions to α,β-dichloroaldehydes, kinetic resolutions of complex chlorinated vinyl epoxide intermediates, and Z-selective alkene cross metatheses of cis-vinyl epoxides. This strategy facilitated the synthesis of enantioenriched danicalipin A, mytilipin A, and malhamensilipin A in nine, eight, and 11 steps, respectively.",10.1021/jo5000829,2014-02-04,0.5971799796423681
Journal of Organic Chemistry,Total Synthesis of Buergerinin F and Buergerinin G,Syntheses of buergerinin F (1) and buergerinin G (2) were carried out to establish the absolute stereochemistry of these natural products. A linear sequence was used to synthesize 1 in 15 steps and 9% overall yield from thymidine. Subsequent oxidation of 1 with ruthenium tetroxide afforded 2 in 77% yield.,10.1021/jo0341620,2003-04-22,0.5971758504400914
Synthesis,Synthesis of New 3-(-2-Alkenyl)-2-hydroxy-5-methoxy-<i>p</i>-benzoquinones via Claisen Rearrangement of Original 5-Methoxy-4-(2-propenyloxy)-<i>o</i>-benzoquinones,"All articles of this category The Claisen rearrangement is extended to compounds containing the benzoquinone moiety, obtained by regioselective nucleophilic substitution on 4-( p -methoxyphenoxy)-5-methoxy-o-benzoquinone (1) . In the most general case, 5-methoxy-4-(2-propenyloxy)- o -benzoquinones 3 rearrange quantitatively into ( E )-3-(2-alkenyl-2-hydroxy-5-methoxy- p -benzoquinones 4 . Furfuryl or (2-thienyl)methyl ethers isomerize to 3-(2-methyl-3-furyl)- and 3-(2-methyl-3-thienyl)-2-hydroxy-5-methoxy- p -benzoquinones. This new synthetic method provides an efficient route to new hydroxybenzoquinones closely related to natural compounds. Thus, dihydroardisiaquinone A is synthesized in 5 steps from p -methoxyphenol.",10.1055/s-1988-27547,1988-01-01,0.5971471546641554
Tetrahedron,Stereoselective total synthesis of preclavulone-A methyl ester and its diastereomer,,10.1016/j.tetlet.2003.12.140,2004-01-27,0.5971444074966618
Journal of Organic Chemistry,Synthesis of the β<sub>3</sub>-Adrenergic Receptor Agonist Solabegron and Analogous <i>N</i>-(2-Ethylamino)-β-amino Alcohols from <i>O</i>-Acylated Cyanohydrins – Expanding the Scope of Minor Enantiomer Recycling,"A novel methodology to produce highly enantioenriched N-(2-ethylamino)-β-amino alcohols was developed. These compounds were obtained from O-(α-bromoacyl) cyanohydrins, which were synthesized by the minor enantiomer methodology employing a Lewis acid and a biocatalyst, followed by nucleophilic substitution with amines and reduction. The importance of the developed methodology was demonstrated by completing a highly enantioselective total synthesis of the β3-adrenergic receptor agonist Solabegron.",10.1021/acs.joc.5b00322,2015-02-17,0.5971352771402226
Tetrahedron,"A new route to bis(2,4,6-tri-tert-butylphenyl)diphosphene via silylated compound",,10.1016/s0040-4039(00)87671-6,1982-01-01,0.5971290969299774
Journal of the American Chemical Society,Total Synthesis and Structural Validation of Phosdiecin A via Asymmetric Alcohol-Mediated Carbonyl Reductive Coupling,The first total synthesis and structural validation of phosdiecin A was accomplished in 13 steps through asymmetric iridium-catalyzed alcohol-mediated carbonyl reductive coupling. The present route is the shortest among >30 total and formal syntheses of fostriecin family members.,10.1021/jacs.9b07512,2019-08-21,0.5971263757187293
Organic Letters,A Simple Route to Polysubstituted Indoles Exploiting Azide Induced Furan Ring Opening,"A straightforward, efficient indole synthesis based on thermolysis of 2-(2-azidobenzyl)furans with attack of the formed nitrene moiety onto the ipso position of furan ring has been developed. The cyclization is accompanied by furan ring opening and affords indoles with a 2-acylvinyl substituent suitable for further modifications.",10.1021/ol5018504,2014-08-01,0.5971202503726131
Tetrahedron,Synthesis of an analog of biosynthetic precursor Ia of lipid A by an improved method: a novel antagonist containing four (S)-3-hydroxy fatty acids,,10.1016/0040-4039(95)01433-0,1995-10-01,0.5971180983789203
Journal of Organic Chemistry,Novel Sesquiterpenoids from the Fermentation of <i>Xylaria </i><i>p</i><i>ersicaria</i> Are Selective Ligands for the NPY Y5 Receptor,"Neuropeptide Y (NPY) is a polypeptide found in the peripheral and central nervous system and is involved in the regulation of feeding. Antagonists of NPY receptor activation could therefore have potential for development as antiobesity drugs. Fermentation of an isolate of Xylaria persicaria yielded two novel eremophilane sesquiterpenoids xylarenals A (1) and B (2). These compounds are selective for the NPY Y5 receptor but have only modest affinity. The isolation, structure elucidation, and biological activities of these compounds are described.",10.1021/jo011054+,2002-06-14,0.5971158117768686
Organic Letters,"Palladium-Induced Cyclizations for the Synthesis of <i>cis</i>-2,5-Disubstituted-3- methylenetetrahydrofurans:  Studies of the C<sub>7</sub>−C<sub>22</sub> Core of Amphidinolide K","[formula: see text] The diastereoselective synthesis of cis-2,5-disubstituted-3-methylenetetrahydrofurans via Pd(0)-catalyzed cyclization of 2-methylene-1,4-diols is described. Investigations into the scope of the reaction and its application toward the synthesis of amphidinolide K is reported.",10.1021/ol990255l,1999-09-24,0.5971093090277207
Journal of the American Chemical Society,Asymmetric Synthesis of (−)-Anatoxin-a via an Asymmetric Cyclization Using a New Ligand for Pd-Catalyzed Alkylations,"Palladium-catalyzed asymmetric allylic alkylations have been explored in the context of medium-sized ring substrates, intramolecular vs intermolecular processes involving attack on a formally meso π-allyl intermediate in the desymmetrization, and the presence of electron-withdrawing groups on the cationic π-allylpalladium intermediate. The synthesis of anatoxin-a, also known as the “very fast death factor”, raises all of these questions. Ligands derived from trans -1,2-diaminocyclohexane and 2-diphenylphosphinobenzoic acid effect asymmetric alkylations with an allyl substrate bearing an electron-withdrawing group. On the other hand, a new type of ligand wherein the diamine is derivatized with both 2-diphenylphosphinobenzoic acid and 2-picolinic acid was required to effect asymmetric cyclization to form the 9-azabicyclo[4.2.1]non-2-ene system. A total synthesis of anatoxin-a from 5-hydroxy-1,8-nonadiene employing a metathesis reaction to form the cycloheptene and a palladium-catalyzed asymmetric cyclization to form the bicyclic ring system is achieved in 15% overall yield.",10.1021/ja983617d,1999-03-19,0.5971078173420371
Journal of the American Chemical Society,Enantiospecific Total Synthesis of the Highly Strained (−)-Presilphiperfolan-8-ol via a Pd-Catalyzed Tandem Cyclization,"A rare element of high strain in molecules of natural origin is a 1,2-trans fusion of 5-membered rings within a [3.3.0]-bicycle, a motif present in (-)-presilphiperfolan-8-ol. This molecule also possesses a 1,3-trans stereochemical arrangement of substituents on one of its 5-membered rings, a pattern shared by a number of other terpenes. Herein, we disclose the first total synthesis of this highly strained target in 13 steps. The key operation is a Pd-catalyzed tandem cyclization that directly establishes the requisite 1,3-trans stereochemical arrangement on one ring while concurrently setting the stage for the controlled generation of the highly strained 1,2-trans ring fusion of the final architecture.",10.1021/jacs.7b01454,2017-03-29,0.5971046489740705
Angewandte Chemie International Edition,Inside Cover: One‐Pot High‐Yielding Synthesis of the DPP4‐Selective Inhibitor ABT‐341 by a Four‐Component Coupling Mediated by a Diphenylprolinol Silyl Ether (Angew. Chem. Int. Ed. 12/2011),"The dipeptidyl peptidase IV selective inhibitor ABT-341 was synthesized by an uninterrupted sequence of reactions in excellent yield with excellent diastereo- and enantioselectivity. Y. Hayashi et al. describe in their Communication on page 2824 ff. how a diphenylprolinyl silyl ether mediates the sequence of an asymmetric Michael reaction, a domino Michael/Horner–Wadsworth–Emmons reaction combined with a retro-aldol reaction, a base-catalyzed isomerization, an amide bond formation, and a reduction of the nitro group to an amine.",10.1002/anie.201100625,2011-02-21,0.5971018985999654
Tetrahedron,Convergent stereocontrolled synthesis of substituted exo-glycals by Stille cross-coupling of halo-exo-glycals and stannanes,,10.1016/j.tetlet.2006.06.133,2006-07-19,0.5971005788626408
Tetrahedron,Dimerization of substituted 2-aminobenzoic acids under Vilsmeier conditions: A novel route to the synthesis of 4-(3H)-quinazolinones,,10.1016/0040-4039(96)01022-2,1996-07-01,0.5970954207275934
Synthesis,"Regio- and Stereospecific Total Synthesis of a Racemic A,19-Dinorsteroid","All articles of this category DL-A-nor-estr-3(5)-ene-2,17-dione is regio- and stereospecifically synthesized from 1-acetal-protected 7a-methyl-2,3,5,6,7,7a-hexa- hydroindene-1,5-dione in five steps in ca. 23% overall yield. The key step is the regiospecific trapping of an enolate of the dione with 6,6-(1,2-ethanediyldioxy)-2-trimethylsilyl-3-oxo-1-heptene.",10.1055/s-1990-27026,1990-01-01,0.597082966385871
Tetrahedron,"Synthesis of bioactive indolocarbazoles: synthesis, nucleophilic ring-opening and chiral base desymmetrisation of a cyclic sulfate intermediate",,10.1016/j.tetlet.2004.08.058,2004-08-31,0.5970820892200608
Tetrahedron,A novel method for the synthesis of purine α-ribonucleosides,,10.1016/s0040-4039(00)89898-6,1968-01-01,0.5970782280159549
Tetrahedron,A novel method for the synthesis of 2-imidazolones,,10.1016/j.tetlet.2010.02.030,2010-02-12,0.5970782280159549
Tetrahedron,A novel method for the synthesis of 2-oxazolines,,10.1016/j.tetlet.2022.154048,2022-07-28,0.5970782280159549
Tetrahedron,"A novel method for the synthesis of 2,2-diaryl-1,1-difluoroethenes",,10.1016/j.tetlet.2007.12.028,2008-01-15,0.5970782280159549
Tetrahedron,"A novel method for the synthesis of 2,5-diarylselenophenes",,10.1016/s0040-4039(02)00894-8,2002-07-01,0.5970782280159549
Tetrahedron,A novel method for the synthesis of 1-aryltetrahydroisoquinolines,,10.1016/j.tetlet.2016.11.115,2016-12-18,0.5970782280159549
Tetrahedron,A novel fluorinating method for the synthesis of α-fluoroketones,,10.1016/s0040-4039(01)93557-9,1979-01-01,0.5970782280159549
Tetrahedron,Novel method for the synthesis of dinucleoside-(N3′ →P5′)-phosphoramidothioates,,10.1016/j.tetlet.2017.04.094,2017-04-29,0.5970782280159549
Tetrahedron,A novel method for the synthesis of phenanthrenes and benzo[a]carbazoles,,10.1016/s0040-4039(98)01919-4,1998-11-01,0.5970782280159549
Tetrahedron,A novel method for the synthesis of 4(3H)-quinazolinones,,10.1016/j.tetlet.2004.03.003,2004-03-20,0.5970782280159549
Angewandte Chemie International Edition,Chemoproteomics‐Enabled Discovery of a Potent and Selective Inhibitor of the DNA Repair Protein MGMT,"We present a novel chemical scaffold for cysteine-reactive covalent inhibitors. Chloromethyl triazoles (CMTs) are readily accessed in only two chemical steps, thus enabling the rapid optimization of the pharmacological properties of these inhibitors. We demonstrate the tunability of the CMTs towards a specific biological target by synthesizing AA-CW236 as the first potent non-pseudosubstrate inhibitor of the O(6) -alkylguanine DNA methyltransferase (MGMT), a protein of major clinical significance for the treatment of several severe cancer forms. Using quantitative proteomics profiling techniques, we show that AA-CW236 exhibits a high degree of selectivity towards MGMT. Finally, we validate the effectiveness of our MGMT inhibitor in combination with the DNA alkylating drug temozolomide in breast and colon cancer cells by fluorescence imaging and a cell-viability assay. Our results may open a new avenue towards the development of a clinically approved MGMT inhibitor.",10.1002/anie.201511301,2016-01-22,0.597077741874204
Journal of Organic Chemistry,Synthesis and Biological Activities of Scleropentaside D,"We report the first total synthesis of scleropentaside D, a unique C -glycosidic ellagitannin, from the ketal derivative of scleropentaside A employing site-selective O4-protection of C -acyl glycoside and copper-catalyzed oxidative coupling reaction of galloyl groups as the key steps. Our study confirms the proposed structure of this natural product, scleropentaside D, and demonstrates its effectiveness as an inhibitor of α-glycosidase.",10.1021/acs.joc.4c00755,2024-06-11,0.5970668125216816
Angewandte Chemie International Edition,Efficient Synthesis of (−)‐Corynoline by Enantioselective Palladium‐Catalyzed α‐Arylation with Sterically Hindered Substrates,"Sterically hindered substrates can be employed in an enantioselective palladium-catalyzed α-arylation with the chiral monophosphorus ligand BI-DIME. This process enabled an efficient synthesis of the antidepressant (S)-nafenodone, a four-step enantioselective synthesis of the Sceletium alkaloid (+)-sceletium A-4, a concise five-step enantioselective synthesis of (-)-corynoline, as well as a three-step preparation of (-)-DeN-corynoline.",10.1002/anie.201807302,2018-08-07,0.5970650779136261
Organic Letters,Divergent Total Synthesis of Diterpenoid Natural Products from <i>Salvia miltiorrhiza</i>,"Herein we report a divergent strategy culminating in the first total synthesis of five terpene natural products isolated from Salvia miltiorrhiza . This approach features efficient construction of a functionalized tetralin core, a scalable route to a furan coupling partner, and a direct C–H borylation. An operationally simple HFIP-mediated benzylic C–H lactonization allowed late-stage diversification through Pd-catalyzed carbonylation and biaryl coupling, providing concise access to multiple natural products from a common intermediate.",10.1021/acs.orglett.5c04440,2025-12-12,0.5970396741947551
Organic Letters,"Acid-Mediated Intermolecular [3 + 2] Cycloaddition toward Pyrrolo[2,1-<i>a</i>]isoquinolines: Total Synthesis of the Lamellarin Core and Lamellarin G Trimethyl Ether","A novel one-pot reaction has been developed for the efficient synthesis of pyrrolo[2,1-a]isoquinolines and 1-dearyllamellarin core from (E)-(2-nitrovinyl)benzenes and azomethine ylides generated in situ. This strategy provides a concise total synthesis of the lamellarin core and lamellarin G trimethyl ether using electrophilic substitution and palladium-catalyzed Suzuki-Miyaura cross-coupling reactions.",10.1021/acs.orglett.7b00769,2017-04-19,0.5970378500685094
Organic Letters,Asymmetric Synthesis of New Chiral β-Amino Acid Derivatives by Mannich-type Reactions of Chiral <i>N</i>-Sulfinyl Imidates with <i>N</i>-Tosyl Aldimines,"New chiral beta-(sulfonylamino)sulfinylimidates are synthesized in high overall yield and excellent diastereomeric excess via highly anti-selective Mannich-type reactions of chiral N-tert-butanesulfinyl imidates with N-tosyl aldimines. Deprotection of the beta-(sulfonylamino)sulfinylimidates gave access to enantiopure imidate hydrochlorides in high yields, as useful intermediates for an easy transformation to new chiral beta-sulfonylamino amides upon simple heating in chloroform. Hydrolysis of the imidate hydrochlorides afforded the corresponding chiral beta-sulfonylamino esters with >98% ee as new chiral beta-amino acid derivatives.",10.1021/ol100073y,2010-04-02,0.597033765295733
Synlett,Baylis-Hillman Protocol in an Enantiocontrolled Synthesis of Pentenomycin I,All articles of this category A new route to the cyclopentanoid antibiotic (-)-pentenomycin I 1 has been developed by application of the Baylis-Hillman reaction on the chiral cyclopentadienone synthon. pentenomycin I - enantiocontrolled synthesis - chiral building block - Baylis-Hillman reaction - chiral cyclopentadienone,10.1055/s-1999-2650,1999-04-01,0.5970326001431234
Organic Letters,Formal Total Synthesis of RK-397 via an Asymmetric Hydration and Iterative Allylation Strategy,"A formal total synthesis of the oxopentaene macrolide antibiotic RK-397 has been achieved. Nine stereocenters were established by a combination of allylation and our asymmetric hydration reactions and a 1,5 anti-selective aldol reaction. The synthesis proceeded in 19 steps from simple achiral conjugated dienoates.",10.1021/ol801055b,2008-06-13,0.5970310034065741
Organic Letters,Pd-Catalyzed Enantioselective Double C–H Activation and Transmetalation: Synthesis of 2-Heteroaryl/aryl-Ferrocenealdehydes,"Synthesis of heterocycle-derived chiral ferrocene formaldehydes opens a new avenue for planar chiral ligands, catalysts, and chiral materials. Herein, Pd II /MPAA catalyzed enantioselective double C–H activation, an arylation-oxidative deamination strategy, leads to a step-economical synthetic route for regioselective, monoselective, and enantioselective new heterocycle-substituted chiral ferrocene formaldehydes. The developed methodology is quite general to provide indolizinyl, indolyl, pyrrolyl, furanyl, thiophenyl, oxazolyl, thiazolyl, and aryl-substituted platform ferrocene formaldehydes with up to 60% yield and 97:3 er.",10.1021/acs.orglett.5c04004,2025-10-17,0.5970301879941465
Synthesis,"Synthesis of 2-Chloro-2’-5’-dideoxy-5’-difluoromethylphosphinyladenosine: A Nonhydrolyzable Isosteric, Isopolar Analog of 2-Chlorodeoxyadenosine Monophosphate","All articles of this category 2-Chloro-2’-5’-dideoxy-5’-difluoromethylphosphinyladenosine (5) was synthesized in thirteen steps from 3- O -benzyl-1,2- O -isopropylidene -α -D-ribofuranoside (1) , a carbohydrate which is substituted differently at the 2- and 3-positions, making possible selective deprotection and reductive deoxygenation at the 2’-position of a nucleoside subsequent to glycosylation. Purine nucleoside phosphonate 5 is an analog of the monophosphate ester of the potent, clinically effective immunomodulatory agent 2-chlorodeoxyadenosine (2-CdA), and was synthesized to present a potential means of circumventing drug resistance in target immune cells. 2-chlorodeoxyadenosine - nonhydrolyzable nucleotide analogs - drug resistance - difluoromethyl phosphonates",10.1055/s-1996-4314,1996-07-01,0.5970271058700496
Organic Letters,Total Synthesis of the Tetracyclic Lupin Alkaloid (+)-Allomatrine,"(+)-Allomatrine (1) has been synthesized using an imino-aldol reaction and N-acyliminium cyclization as key steps. Strategically, use of the tert-butylsulfinimine derivative of (E)-4-(trimethylsilyl)but-2-enal enabled the staged formation of three C-C bonds, a C-N bond, and the four stereogenic centers within the target.",10.1021/ol402198n,2013-08-27,0.5970232864004467
Organic Letters,Synthesis of (+)-Tacamonine via Stereoselective Radical Cyclization,"A concise, asymmetric synthesis of the indole alkaloid (+)-tacamonine is reported involving a stereoselective radical cyclization of a 1-phenylsulfanyl tetrahydro-β-carboline bearing a pendant enoate ester side chain as a key step. In this process, a single stereocenter in the side chain allows for the formation of two stereocenters of the natural product in a highly diastereoselective fashion. Computational investigations of this key cyclization support the experimentally observed outcome and shed light on the factors impacting its stereoselectivity.",10.1021/acs.orglett.9b03308,2019-10-24,0.5970163530412288
Tetrahedron,"First total synthesis of 25(R)-ruscogenin-1-yl β-D-xylopyranosyl-(1→3)-[β-D-glucopyranosyl-(1→2)]-β-D-fucopyranoside, an ophiopogonis saponin from the tuber of Liriope muscari (Decne.)",,10.1016/s0040-4039(97)10536-6,1998-01-01,0.5970161329198105
Journal of Organic Chemistry,A Convergent Synthesis of Hexahomotriazacalix[3]arene Macrocycles,"A new, convergent synthesis of hexahomotriazacalix[3]arenes 1a-e is described. The key transformation in this synthesis involves the coupling of the triamines 4a-d with 2, 6-bis(chloromethyl)-4-methylphenol 5 and results in the formation of the hexahomotriazacalix[3]arenes 1a-d in 90-95% yield. The triamines 4a-d were constructed by the one-pot reaction of monochloroaldehyde 3 and a primary amine followed by reduction to yield the triamines 4a-d in 50-55% yield. Deallylation of macrocycle 1d was accomplished by palladium catalysis to obtain the N-unsubstituted macrocycle 1e, which has the potential to be a precursor to a variety of N-substituted hexahomotriazacalix[3]arenes.",10.1021/jo001094y,2000-11-03,0.5970040308590876
Journal of Organic Chemistry,"Efficient Conversion of Biginelli 3,4-Dihydropyrimidin-2(1<i>H</i>)-one to Pyrimidines via PyBroP-Mediated Coupling","An efficient two-step procedure is described to convert the Biginelli 3,4-dihydropyrimidin-2(1H)-one to various multifunctionalized pyrimidines via the Kappe dehydrogenation and a new mild PyBroP-mediated coupling with C, N, O, and S nucleophiles, which provides a readily accessible multifunctionalized pyrimidine template for diversity-oriented synthesis.",10.1021/jo040281j,2005-02-03,0.5969994519239352
Organic Letters,Convergent Assembly of the Spiroacetal Subunit of Didemnaketal B,A highly convergent synthesis of the C9-C28 spiroacetal subunit of didemnaketal B has been accomplished. Assembly of the C9-C15 alkylborate and C16-C21 enol phosphate by means of Suzuki-Miyaura coupling and acid-catalyzed cyclization of the derived dihydroxy enol ether enabled a rapid and efficient construction of the spiroacetal subunit. The C22-C28 side chain was incorporated via Nozaki-Hiyama-Kishi coupling to complete the synthesis.,10.1021/ol1024713,2010-10-28,0.596998068683792
Journal of Organic Chemistry,Synthesis of C-5 Analogs of <i>N</i>-Acetylneuraminic Acid via Indium-Mediated Allylation of N-Substituted 2-Amino-2-deoxymannoses,"This paper presents a short synthesis of new analogs of N-acetylneuraminic acid (Neu5Ac) varied structurally at C-5. The synthetic strategy includes indium-mediated coupling reactions between ethyl 2-(bromomethyl)acrylate and N-derivatized mannosamines, and the ozonolysis of the resulting enoates. The main advantage of this indium-mediated allylation for the synthesis of neuraminic acids comes from the efficient, stereoselective C-C bond formation, which affords predominantly the correct diastereomer having a threo relationship between the newly generated hydroxyl group and the C-2 amide group of mannosamine. By this approach, Neu5Boc (4a), Neu5Gly (4b), Neu5(6-NHCbz)hexanoyl (4c), and Neu5(1-naphthyl)acetyl (4d) were prepared in three steps (overall approximately 50%). In addition, several N-substituted neuraminic acids were synthesized by N-acylation of the amino functionality of neuraminic acid (5b), which was obtained by deprotecting the N-Boc group of Neu5Boc (4a). These analogs include Neu5BrAc (6a), Neu5acryloyl (6b), Neu5benzoyl (6c) and Neu5benzoyl-4-benzoyl (6d). The N-acylation method is especially suited for synthesis of neuraminic acids bearing substituents that can not tolerate ozonolysis or that are unstable (photo)chemically. Finally, we illustrate the utility of synthetic neuraminic acids by converting 4c to a derivative of 2-deoxy-2,3-didehydroneuraminic acid (8c), a precursor to inhibitors of neuraminidases.",10.1021/jo9614856,1996-01-01,0.5969972860520317
Synthesis,Enantioselective Synthesis of (S)-2-Amino-3-(3-Hydroxy-5-methylisoxazol-4-yl)propanoic Acid (S)-AMPA,"All articles of this category ( S )-AMPA (11) is an isoxazole containing α -amino acid used for selectively labeling the homonymous excitatory amino acid (EAA) receptor. Until now only enzymatic methods have been devised for its preparation. An asymmetric synthesis of ( S )-AMPA is reported which exploits the formation of 3-bromo-4-hydroxymethyl-5-methylisoxazole intermediate 3 in a potassium fluoride promoted 1,3-dipolar cycloaddition and the application of the bislactim ether methodology for introducing the chiral α -amino acid center. 1,3-dipolar cycloaddition - bromonitrile oxide - isoxazole - Schöllkopf method - ( S )-AMPA",10.1055/s-1996-4357,1996-10-01,0.5969964097366595
Tetrahedron,Synthesis of stereodefined fused δ-hydroxy-γ-lactones from dealkylative cyclization of epoxy-diesters,,10.1016/j.tetlet.2011.06.106,2011-07-07,0.5969815496801292
Angewandte Chemie International Edition,"Enantioselective Total Synthesis of the Highly Oxygenated 1,10‐<i>seco</i>‐Eudesmanolides Eriolanin and Eriolangin","Sultones of swing: A sultone served as the key intermediate in the first enantioselective total syntheses of the bioactive title compounds (see scheme), the absolute configuration of which is now established. Starting from 2-bromo-1-(2-furyl)ethanone, 24 steps were required to generate the common basic structure, and in each case two additional steps yielded the natural products.",10.1002/anie.200460936,2004-11-10,0.5969779108624137
Organic Letters,Improved Synthesis of the Two-Photon Caging Group 3-Nitro-2-Ethyldibenzofuran and Its Application to a Caged Thymidine Phosphoramidite,"A new and efficient route to the recently reported 3-nitro-2-ethyldibenzofuran caging group was developed. Furthermore, its installation on a thymidine phosphoramidite is described. This caging group is efficiently removed through light-irradiation at 365 nm.",10.1021/ol902807q,2010-01-29,0.5969742093644883
Organic Letters,Asymmetric Annulation toward Pyrrolopiperazinones:  Concise Enantioselective Syntheses of Pyrrole Alkaloid Natural Products,"A novel Pd-catalyzed asymmetric annulation between 5-bromopyrrole-2-carboxylate esters and vinyl aziridines has been developed to efficiently construct pyrrolopiperazinones, which can serve as key intermediates in the enantioselective syntheses of pyrrole alkaloid natural products. In this paper, the total synthesis of (-)-longamide B in five steps and the first total syntheses of agesamides A and B in six steps from 6 and 7 are reported.",10.1021/ol070742y,2007-05-12,0.5969731753065127
Journal of Organic Chemistry,"Stereocontrolled Synthesis of Polyfunctionalized <i>cis</i>-Decalins from 2-Methoxyphenols:  Total Syntheses of (±)-Eremopetasidione, (±)-3β-Angeloyloxyfuranoeremophilane, and (±)-3β-Methacryloyloxyfuranoeremophilane","A four-step stereocontrolled synthesis of polyfunctionalized cis-decalins is described, involving oxidation of 2-methoxyphenol, intermolecular Diels-Alder reaction, olefination, and Cope rearrangement. Application of this efficient strategy to the total syntheses of (+/-)-eremopetasidione, (+/-)-3 beta-angeloyloxyfuranoeremophilane, and (+/-)-3 beta-methacryloyloxyfuranoeremophilane was accomplished from creosol and ethyl vinyl ketone via a common intermediate 21.",10.1021/jo702115x,2008-03-07,0.596968826180064
Journal of Organic Chemistry,Regioconvergent Synthesis of a π-Extended Tribenzotriquinacene-Based Wizard Hat-Shaped Nanographene,"The successful enlargement of the curved π-electron periphery of the wizard hat-shaped polycyclic aromatic compound 1 is described. The target structure 2 features an m, m, p, m, m, p, m, m, p -nonaphenylene belt fused to a central tribenzotriquinacene unit. The synthesis involves a multiple regioconvergent Scholl-type dehydrocyclization as the key step. Spectroscopic, structural, and electronic properties of the title compound 2 are reported.",10.1021/acs.joc.1c00059,2021-04-07,0.5969672440878862
Synthesis,"1,5-Anhydro-<scp>d</scp>-fructose as Chiral Building Block: A Novel Approach to 1-Deoxymannojirimycin","A novel six-step synthesis of 1-deoxymannojirimycin from 1,5-anhydro-d-fructose in 35% overall yield is reported. The key steps are nucleophilic piperidine ring formation and subsequent Lewis acid induced pyran ether cleavage.",10.1055/s-2006-926343,2006-01-01,0.5969635627950273
European Journal of Organic Chemistry,"First Stereoselective Synthesis of (1<i>R</i>,2<i>R</i>,4<i>R</i>)‐ and (1<i>S</i>,2<i>R</i>,4<i>S</i>)‐2‐Substituted‐1‐azabicyclo[2.2.1]heptanes","Abstract The first stereoselective synthesis of two diastereomeric 1‐azabicyclo[2.2.1]heptanes substituted at the 2‐position from an easily accessible ( R )‐2‐substituted‐4‐piperidone is reported. The synthetic route involves the asymmetric one‐carbon homologation of a chiral ketone followed by an intramolecular S N 2‐type cyclisation and led to target compounds in high overall yield by using a simple procedure in which purification of the intermediate compounds is not required. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2009)",10.1002/ejoc.200801216,2009-02-07,0.5969603484043637
Tetrahedron,"First total synthesis of (±)-epocarbazolin A and epocarbazolin B, and asymmetric synthesis of (−)-epocarbazolin A via Shi epoxidation",,10.1016/j.tetlet.2006.06.095,2006-07-11,0.5969509383833593
Tetrahedron,An efficient approach to the synthesis of 3-vinylidene tetrahydropyrans via Prins-type cyclization,,10.1016/j.tetlet.2005.08.014,2005-09-06,0.5969499801368544
Tetrahedron,"Tin-assisted cyclization for chiral cyclohexane synthesis, an alternative route to (−)-tetrodotoxin skeleton",,10.1016/0040-4039(96)01860-6,1996-11-01,0.5969490728923735
Tetrahedron,Construction of a kinase inhibitor library via parallel synthesis,,10.1016/s0040-4039(01)02140-2,2002-01-01,0.5969467847782988
Journal of the American Chemical Society,Total Synthesis of Hybocarpone and Analogues Thereof. A Facile Dimerization of Naphthazarins to Pentacyclic Systems,"The total synthesis of the lichen-derived antitumor agent hybocarpone (1) and related compounds is described. The successful route to hybocarpone features a novel radical-based dimerization/hydration cascade which generates the bridging hindered carbon-carbon bond of the molecule in a stereocontrolled manner, setting the relative configurations of the four contiguous stereocenters in a single step. The conjecture is made that this process may not be so dissimilar to the biosynthetic pathway leading to the formation of hybocarpone in nature. The developed sequence to these molecular frameworks also features the first example of a synthetically useful Diels-Alder trapping of a photochemically generated hydroxy-o-quinodimethane species with a 1,1-disubstituted olefin to form a quaternary center, and includes an efficient route to hydroxynaphthoquinone-type structures represented by the monomeric subunit of the natural product.",10.1021/ja030497n,2003-12-17,0.5969421827948265
Tetrahedron,A very short route to the functionalized A-ring moiety of ciguatoxin,,10.1016/s0040-4039(99)02185-1,2000-02-01,0.5969379971752604
Journal of Organic Chemistry,Stereoselective and Efficient Total Synthesis of Optically Active Tetrodotoxin from <scp>d</scp>-Glucose,A stereoselective and efficient total synthesis of optically active tetrodotoxin (TTX) is described. A polyfunctionalized key cyclitol compound containing branched-chains for the synthesis of TTX was prepared from D-glucose employing the Henry reaction (Nitro aldol reaction) as the key transformation. Stereoselective construction of the alpha-azido-aldehyde branched-chain was achieved via the key spiro alpha-chloroepoxide intermediate.,10.1021/jo701655v,2008-01-19,0.5969370416213445
Organic Process Research & Development,"Process Development for (<i>S,S</i>)-Reboxetine Succinate via a Sharpless Asymmetric Epoxidation","Reboxetine mesylate is a selective norepinephrine uptake inhibitor (NRI) currently marketed as the racemate. The ( S,S )-enantiomer of reboxetine is being evaluated for the treatment of neuropathic pain and a variety of other indications. ( S,S )-Reboxetine has usually been prepared by resolution of the racemate as the (−)-mandelate salt, an inherently inefficient process. A chiral synthesis starting with a Sharpless asymmetric epoxidation of cinnamyl alcohol to yield ( R,R )-phenylglycidol was developed. ( R,R )-Phenylglycidol was reacted without isolation with 2-ethoxyphenol to give 4, which was isolated by direct crystallization. Key process variables for the asymmetric epoxidation were investigated. Conversion of ( R,S )- 4 to reboxetine parallels the racemic synthesis with streamlined and optimized processing conditions. ( S,S )-Reboxetine free base was converted directly to the succinate salt without isolation as the mesylate salt.",10.1021/op700007g,2007-03-23,0.5969323946748778
Organic Letters,Total Synthesis of (+)-Crocacin C,"The total synthesis of (+)-crocacin C is described. The convergent asymmetric synthesis relies on the use of a regio- and diastereoselective epoxidation of an allylic alcohol with m-CPBA followed by epoxide opening with Me(2)CuCNLi(2) and a Stille cross-coupling between E-vinyl stannane 5 and E-vinyl iodide 6 to establish the (E,E)-dienamide moiety. [structure: see text]",10.1021/ol016845c,2001-11-01,0.5969297127421732
Tetrahedron,Asymmetric synthesis of 1-substituted-1-(pyridin-2-yl)methylamines by diastereoselective reduction of enantiopure N-p-toluenesulfinyl ketimines,,10.1016/j.tetlet.2005.06.019,2005-07-06,0.596917434806271
Organic Letters,Total Synthesis of (±)-Meloscine,"The total synthesis of (±)-meloscine was completed in a highly stereoselective manner starting from the known 4-(2-aminophenyl)-2,3-dihydro-N-methoxycarbonylpyrrole. The crucial step in this total synthesis involves the efficient construction of the tetracyclic framework of the target natural product by the intramolecular Pauson-Khand reaction.",10.1021/ol200311y,2011-03-07,0.5969164296213346
Tetrahedron,Asymmetric synthesis. XXXV1. Synthesis of 2-methyl 5-substituted substituted piperidines from chiral non-racemic lactams,,10.1016/0040-4039(94)02435-e,1995-02-01,0.5969152278796382
Journal of Organic Chemistry,"Asymmetric Synthesis of (−)-7-Epiaustraline and (+)-1,7-Diepiaustraline","A diastereoselective and modular approach to the synthesis of the 3-hydroxymethyl-2,3,5,6,7,7a-hexahydro-1H-pyrrolizine-1,2,7-triol structure, characteristic of several natural pyrrolizidine natural products, has been developed. This approach culminated in the synthesis of (-)-7-epiaustraline and (+)-1,7-diepiaustraline. The oxazolidinone group has been found to be a useful protecting group in the RCM reaction and, as part of a pyrrolo[1,2-c]oxazol-3-one ring system, has functioned as a stereo- and regio-directing group in a key diastereoselective cis-dihydroxylation reaction and a regioselective nucleophilic ring-opening of a S,S-dioxo-dioxathiole.",10.1021/jo034914q,2003-09-06,0.5969057760267472
Synthesis,Synthesis of a Substituted Benzazepin-2-one Dihydrate,"Synthesis of the title compound was accomplished via coupling of (S)-alaninyl-(S)-1-amino-3-methyl-4,5,6,7-tetrahydro-2H-3-benzazepin-2-one with the activated trimethylsilyl ester of (S)-2-trimethylsilyloxy-3-methylbutyric acid, followed by deprotection and crystallization in situ. The starting material was prepared by the condensation of (S)-1-amino-3-methyl-4,5,6,7-tetrahydro-2H-3-benzazepin-2-one with activated N-(2-methoxycarbonyl-1-methylvinyl)-(S)-alanine sodium salt in the form of the mixed carboxylic carbonic anhydride, followed by enamine hydrolysis using methanesulfonic acid.",10.1055/s-0029-1216813,2009-05-14,0.5969056678908754
Organic Letters,Total Synthesis of (+)-Eburnamonine Using Asymmetric Alkene Cyanoamidation through C–CN Bond Activation,"We report the total synthesis of (+)-eburnamonine using enantioselective alkene cyanoamidation to form the all-carbon quaternary stereocenter. Palladium, phosphoramidite ligand, and a Lewis acid combine to form a co-catalyst that promotes C-CN activation of a cyanoformamide, followed by intramolecular alkene cyanoamidation. Overall, the synthesis of (+)-eburnamonine is accomplished in 8 steps from 4-methylene hexanoic acid and tryptamine, providing an example of asymmetric aliphatic-tethered alkene cyanoamidation and its use in total synthesis.",10.1021/acs.orglett.4c01480,2024-07-01,0.5968999501303094
Synthesis,"A New Synthesis of 5-Hydroxy-4-oxo-1,4-dihydroquinolines",,10.1055/s-1977-24357,1977-01-01,0.5968920767088307
Journal of the American Chemical Society,Concerning the Antileukemic Agent Jatrophatrione:  The First Total Synthesis of a [5.9.5] Tricyclic Diterpene,"The highly functionalized [5.9.5] tricyclic framework resident in jatrophatrione (1) has been synthesized. The route begins with the tandem anionic oxy-Cope rearrangement/methylation/transannular ene cyclization of 5 and subsequent introduction of a conjugated enone double bond. Hydroxyl-directed 1,4-reduction of this functionality in 6 with LiAlH4/CuI/HMPA/THF sets the stage for the implementation of a Grob fragmentation and rapid generation of 8. Stereocontrolled intramolecular hydrosilylation allows for the subsequent introduction of a cyclic carbonate as in 11. This intermediate undergoes a remarkably smooth Treibs reaction to generate 12, thus serving as a pivotal step for making 1 available five steps later.",10.1021/ja020292z,2002-05-15,0.5968916000843841
Angewandte Chemie International Edition,Total Synthesis of Microsclerodermin E,"Succumbing to total synthesis: Microsclerodermin E, a 23-membered cyclic hexapeptide possessing antifungal activity, has been prepared for the first time. Key features in the synthesis include the construction of four unusual amino acid units, the assembly of the pyrrolidinone fragment with little racemization, and an effective macrocyclization.",10.1002/anie.200352423,2003-11-04,0.596890879660971
Organic Letters,Total Synthesis of Ciliatamides A-C: Stereochemical Revision and the Natural Product-Guided Synthesis of Unnatural Analogs,"The first total synthesis of Ciliatamides A-C was completed, leading to a revision of the reported stereochemistry from (S,S) to the (R,R) enantiomers. Due to the expedited route, a library of over 50 unnatural ciliatamide analogs was also prepared.",10.1021/ol801842v,2008-09-13,0.5968893829445534
European Journal of Organic Chemistry,Selective Synthesis of New Fluorinated Alicyclic β‐Amino Ester Stereoisomers,Abstract New fluorinated alicyclic β‐amino ester stereoisomers with a cyclohexene or cyclohexane skeleton were prepared from cis ‐ or trans ‐2‐aminocyclohex‐3‐enecarboxylic acids in five or six steps through a regio‐ and stereoselective hydroxylation and hydroxy–fluorine exchange. Fluorinated aminoester enantiomers were synthesized from enantiopure cis ‐ or trans ‐2‐aminocyclohexenecarboxylic acid (prepared byenzymatic resolution of the racemic substances).,10.1002/ejoc.201100583,2011-06-29,0.596883798075381
Synlett,"Transition Metals in Organic Synthesis, Part 82. First Total Synthesis of Methyl 6-Methoxycarbazole-3-carboxylate, Glycomaurrol, the Anti-TB Active Micromeline, and the Furo[2,3-<i>c</i>]carbazole Alkaloid Eustifoline-D","The palladium(0)-catalyzed amination followed by palladium(II)-catalyzed oxidative cyclization of the resulting diaryl­amine provides a short route to a series of 6-oxygenated carbazole alkaloids: glycozoline, 3-formyl-6-methoxycarbazole, methyl 6-methoxycarbazole-3-carboxylate, glycozolinine (glycozolinol), glycomaurrol, micromeline, and eustifoline-D.",10.1055/s-2007-967984,2007-02-01,0.596867702839574
Tetrahedron,"Efficient one-pot synthesis of substituted 2-amino-1,3,4-oxadiazoles",,10.1016/j.tetlet.2008.09.057,2008-09-16,0.5968639511121142
Tetrahedron,"An efficient one-pot synthesis of 3-substituted-5-amino-1,2,4-thiadiazoles from isothiocyanates and amidines",,10.1016/j.tetlet.2008.03.030,2008-03-11,0.5968639511121142
Synthesis,"The First Synthesis of Uralenol, 5′-Prenylated Quercetin, via Palladium-Catalyzed O-Dimethylallylation Reaction with Concurrent Acetyl Migration","The first synthesis of uralenol, 5′-prenylated quercetin, is described. The key step is a palladium-catalyzed O-1,1-dimethylallylation reaction, with concurrent acetyl migration to afford the desired intermediate as a major isomer, which was purified by recrystallization. Finally, Claisen rearrangement, followed by deprotection of all phenolic protecting groups, afforded uralenol in excellent yield.",10.1055/s-0033-1338559,2013-11-22,0.5968406128590976
Tetrahedron,"An efficient synthesis of 4,6-substituted pyrrolo[3,2-d]pyrimidines by silver-catalyzed cyclization of acetylene amine",,10.1016/j.tetlet.2016.04.077,2016-04-30,0.5968352063110068
Journal of the American Chemical Society,Asymmetric Hydrogenation of Thiophenes and Benzothiophenes,"An efficient and highly asymmetric ruthenium-N-heterocyclic carbene-catalyzed hydrogenation of substituted thiophenes and benzothiophenes is described, providing a new strategy for the formation of valuable enantiomerically pure tetrahydrothiophenes and 2,3-dihydrobenzothiophenes.",10.1021/ja306622y,2012-08-31,0.5968265010213142
Synlett,"Total Synthesis of 4α,5α,10β-Trihydroxycadinane and Its <i>C</i><sub>4</sub>-Isomer: Structural Revision of a Natural Sesquiterpenoid","An efficient approach to cadinane sesquiterpenes starting from (R)-carvone, employing a ring closing metathesis (RCM) reaction and a modified allylic diazene rearrangement as key steps, is described. The first asymmetric total syntheses of 4 alpha,5 alpha,10 beta-tri-hydroxycadinane (1) and natural 4 beta,5 alpha, 10 beta-trihydroxycadinane (2) were accomplished and the structure of natural product A was revised to 2.",10.1055/s-2006-951480,2006-09-01,0.5968103122390254
Journal of Organic Chemistry,"Umpolung Flow Chemistry for the Synthesis of a 3-Oxo-3<i>H</i>-spiro[benzofuran-2,4′-piperidine] Building Block","An efficient and scalable route to tert -butyl 3-oxo-3 H -spiro[benzofuran-2,4′-piperidine]-1′-carboxylate, a central prochiral intermediate in the synthesis of SHP2 inhibitor GDC-1971 ( migoprotafib ), was achieved. Preparation of the title compound from readily available 2-fluorobenzaldehyde included formation of a modified Katritzky benzotriazole hemiaminal, which, upon deprotonation by n -butyllithium, participated in umpolung reactivity via 1,2-addition to tert -butyl 4-oxopiperidine-1-carboxylate ( N -Boc-4-piperidone). Most notably, this reaction was developed as a robust plug-flow process that could be executed on multiple kilograms without the need for pilot-scale reaction vessels operating at low cryogenic temperatures. Treatment of the resulting tetrahedral intermediate with oxalic acid resulted in collapse to the corresponding 4-(2-fluorobenzoyl)-4-hydroxypiperidine, which was isolated as a solid via crystallization. The synthesis concluded with an optimized intramolecular S N Ar reaction and final crystallization to generate tert -butyl 3-oxo-3 H -spiro[benzofuran-2,4′-piperidine]-1′-carboxylate as a stable, high-quality intermediate suitable for further functionalization toward GDC-1971 .",10.1021/acs.joc.4c00337,2024-05-20,0.5968100213024974
Tetrahedron,"Cyclizations of 1,2,4-triazinium salts with bifunctional nucleophiles - a new route to condensed 1,2,4-triazines",,10.1016/s0040-4039(00)80316-0,1988-01-01,0.5968087903393894
Organic Letters,"Asymmetric Synthesis of Functionalized, Monocyclic Chlorocyclobutenes",The selective synthesis of a variety of stereopure monocyclic chlorocyclobutenes is described. These derivatives could be coupled with Grignard reagents; two dienes from coupling with vinylmagnesium bromide reacted smoothly with maleic anhydride to yield illudol-related [4 + 2] cycloadducts.,10.1021/ol101559b,2010-08-19,0.5968078383703437
Tetrahedron,A novel cholestane derivative as root growth inhibitor from heloniopsis japonica,,10.1016/s0040-4039(00)92233-0,1992-04-01,0.5968050511986308
Tetrahedron,A new route to 2-fluoro-1-olefins utilizing a synthetic equivalent for the 1-fluoroethene anion,,10.1016/s0040-4039(00)79956-4,1994-02-01,0.5968039746705149
Journal of Organic Chemistry,"Stereoselective Synthesis of <i>meso</i>-2,6-Diaminopimelic Acid and Its Selectively Protected Derivatives","Four synthetic routes to selectively protected derivatives and isomers of meso -diaminopimelic acid (DAP) ( 1a ), a key constituent of bacterial peptidoglycan, were investigated. N -( tert -butyloxycarbonyl)- d -allylglycine ( 2 ) and N -(benzyloxycarbonyl)- l -allylglycine ( 4 ) were esterified to ethylene glycol and cyclized via olefin metathesis to a protected derivative 7 of 2,7-diaminosuberic acid. Analogous linking of propane-1,3-diol with 2 and potential precursors of N -(benzyloxycarbonyl)- l -vinylglycine moieties, such as N -(benzyloxycarbonyl)- l -glutamate or N -(benzyloxycarbonyl)- l -methionine sulfoxide, gave 12 or 15, both of which produced the α,β-unsaturated ester 14 upon attempted generation of the vinylglycine precursor for olefin metathesis to DAP derivatives. An alternative route, based on SnCl 4 -catalyzed ene reaction of methyl N -(benzyloxycarbonyl)- l -allylglycinate ( 18 ) with glyoxylate esters of phenylcyclohexanol isomers as chiral auxiliaries, gave ca. 85:15 ratios of diastereomeric alcohols ( 19 or 20 ). These could be transformed to DAP derivatives in a series of steps employing azide displacement of corresponding mesylates to introduce the second nitrogen. A third method, involving reduction of pure dimethyl ( 6S )-2-keto-6-[ N -(benzyloxycarbonyl)amino]pimelate ( 32 ) to the corresponding alcohol 33 with ( S )-binaphthol−ruthenium catalyst as the key step, gives a 79:21 isomeric ratio. The fourth route employs the bis(oxazoline)−copper complex 41 as a chiral catalyst for the ene reaction of methyl ( S )-4-(phenylthio)allylglycinate ( 39 ) and methyl glyoxylate to afford 42 in 94:6 isomeric ratio. Nickel boride removal of sulfur and the double bond in the presence of the Cbz group gives the desired alcohol, dimethyl (2 S,6 S )-6-[ N -(benzyloxycarbonyl)amino]-2-hydroxyheptane-1,7-dioate ( 33 ). The required selectively protected second nitrogen is introduced using Mitsunobu inversion with N - tert -butyl [[2-(trimethylsilyl)ethyl]sulfonyl]carbamate ( 34 ) as a key step.",10.1021/jo972133h,1998-03-04,0.5968039173510239
Synlett,"A Practical Synthetic Route to Benzofuro[2,3-<i>b</i>]pyridine and Trifluoromethyl-α-carbolines","In situ generated benzofuran-2-amine reacts with 1,3-CCC-dielectrophiles, such as CF3-containing β-diketones, 3-formylchromone, methyl-2,4-dioxopentanoate and pentafluoro­benzaldehyde, and the reaction leads to the formation of benzofuro[2,3-b]pyridine ring system. By using a similar approach 4-trifluoromethyl-α-carbolines were synthesized starting from indole-2-amine.",10.1055/s-2008-1032042,2008-02-01,0.5967940183793051
Organic Letters,Synthesis of the Trisaccharide Repeating Unit of the Atypical <i>O</i>-Antigen Polysaccharide from Danish <i>Helicobacter p</i><i>ylori</i> Strains Employing the 2‘-Carboxybenzyl Glycoside,"[reaction: see text] Synthesis of the unique trisaccharide repeating unit of the O-polysaccharide of the lipopolysaccharide from Danish Helicobacter pylori strains has been accomplished. Key steps include the coupling of three monosaccharide moieties by glycosylations employing the 2'-carboxybenzyl glycoside method. Also presented is a method for the synthesis of the novel branched sugar, 3-C-methyl-D-mannose, which is one of three monosaccharide components.",10.1021/ol048648u,2004-09-29,0.5967911453596413
Chemical Science,"A unified strategy to reverse-prenylated indole alkaloids: total syntheses of preparaherquamide, premalbrancheamide, and (+)-VM-55599","A full account of our studies toward reverse-prenylated indole alkaloids that contain a bicyclo[2.2.2]core is described. A divergent route is reported which has resulted in the synthesis of preparaherquamide, (+)-VM-55599, and premalbrancheamide. An intramolecular Dieckmann cyclization between an enolate and isocyanate was used to forge the bicyclo[2.2.2]diazaoctane core that is characteristic of these molecules. The pentacyclic indole scaffold was constructed through a one-pot Hofmann rearrangement followed by Fischer indole synthesis. The utilization of our previously reported indole peripheral functionalization strategy also led to natural products including malbrancheamides B, C, stephacidin A, notoamides F, I and R, aspergamide B, and waikialoid A. Ultimately, the divergent route that we devised provided access to a wide range of prenylated indole alkaloids that are differently substituted on the cyclic amine core.",10.1039/d0sc02296a,2020-01-01,0.5967902162028008
Organic Letters,Synthesis of Marine Sponge Bisindole Alkaloids Dihydrohamacanthins,"[structure: see text] A convergent synthesis of the marine sponge bisindole alkaloids dihydrohamacanthins is described. The synthesis centers on the construction of 3,5- and 3,6-linked pyrazinones and their reduction to the requisite piperazinones with sodium cyanoborohydride.",10.1021/ol020002j,2002-02-19,0.5967888517789129
Synlett,Concise Synthesis of Potential 4-Hydroxy-5-fluoropentyl Side-Chain Metabolites of Four Synthetic Cannabinoids,"Synthetic cannabinoids are a group of compounds that act on the CB1 receptor and are used illicitly as substitutes for cannabis. Given the rapid and extensive metabolism of synthetic cannabinoids, urinary biomarkers are essential if proof of drug intake is to be obtained in forensic laboratories. To identify good biomarker candidates, the metabolism of synthetic cannabinoids must be studied and reference standards need to be acquired. Studies on the metabolism of synthetic cannabinoids containing a terminally fluorinated pentyl side chain have shown that hydroxylation can occur at the four position of the side chain. This makes the 4-hydroxy-5-fluoropentyl side-chain metabolite a good urinary biomarker for proving intake of the corresponding parent drug, as this compound cannot be formed from its nonfluorinated analogue. Here, a concise synthetic route to the 4-hydroxy-5-fluoropentyl side-chain metabolites of the synthetic cannabinoids STS-135, MAM-2201, AM-2201, and XLR-11 is reported.",10.1055/s-0039-1691571,2020-01-17,0.5967884016142286
Journal of Organic Chemistry,Synthesis of the Antigenic Tetrasaccharide Side Chain from the Major Glycoprotein of <i>Bacillus </i><i>anthracis</i> Exosporium,"A synthesis of the pentenyl glycoside of the tetrasaccharide side chain from the major glycoprotein of Bacillus anthracis by a [3 + 1] approach is described. The construction of the 1,2-trans-glycosidic linkage in the terminal anthrose moiety was achieved through the application of known alpha-nitrilium ion-mediated beta-selective glycosylation methodology. An iterative glycosylation strategy was used for the assembly of the trirhamnan building block. A new route to the anthrose saccharide was developed from D-galactose.",10.1021/jo070750s,2007-07-28,0.5967777417034157
Angewandte Chemie International Edition,Total Synthesis of (−)‐Conophylline and (−)‐Conophyllidine,"Double take: The total syntheses of the title compounds were accomplished in a highly convergent manner. The approach features the regio- and diastereoselective Polonovski–Potier-type reaction for the coupling of two aspidosperma skeletons and the formation of the dihydrofuran ring. Troc=2,2,2-trichloroethoxycarbonyl.",10.1002/anie.201100981,2011-04-15,0.5967730348995426
Tetrahedron,A new route for total synthesis of (±) dephospho Form B of molybdenum cofactor by direct one step thiophene annulation from suitable pterin alkynes,,10.1016/j.tetlet.2013.02.090,2013-03-07,0.5967728104781346
Journal of Organic Chemistry,Asymmetric Synthesis of Both the Enantiomers of <i>trans</i>-3-Hydroxypipecolic Acid,"Both the enantiomers of trans-3-hydroxypipecolic acid have been synthesized employing the Sharpless asymmetric dihydroxylation and epoxidation as the key steps starting from a commercially available starting material 1,4-butanediol.",10.1021/jo0485381,2004-11-26,0.5967678490481827
Tetrahedron,A practical route to enantiopure 3-hydroxy-pyrrolidines: application to a straightforward synthesis of (−)-bulgecinine,,10.1016/j.tetlet.2007.12.051,2008-01-09,0.5967652326169942
Organic Process Research & Development,Large-Scale Synthesis of the Anti-Cancer Marine Natural Product (+)-Discodermolide. Part 1:  Synthetic Strategy and Preparation of a Common Precursor,"The synthetic strategy for producing multigram quantities of (+)-discodermolide ( 1 ) using a hybridized Novartis−Smith−Paterson synthetic route via common precursor 3 is described. In the first part of this five-part series, we present a multikilogram preparation of α-methyl aldehyde 10 from Roche ester, its syn- aldol reaction with Evans boron enolate, removal of the chiral auxiliary, and the preparation of Weinreb amide 3 (Smith common precursor). The common precursor was produced without any chromatography.",10.1021/op034130e,2003-12-04,0.5967621300978375
Angewandte Chemie International Edition,Cover Picture: Modular Synthesis of Triarylmethanes through Palladium‐Catalyzed Sequential Arylation of Methyl Phenyl Sulfone (Angew. Chem. Int. Ed. 3/2014),"Triarylmethanes were prepared in three steps from phenyl methyl sulfone, as described by M. Nambo and C. M. Crudden in their Communication on page 742 ff. After two selective CH arylation reactions, the third aromatic ring was introduced through a novel arylative desulfonation. This sequence permits the synthesis of a wide variety of unsymmetric triarylmethanes from a simple, readily available starting material.",10.1002/anie.201310510,2014-01-08,0.5967570791252517
Organic Letters,"Synthesis of the A,B,C-Ring System of Hexacyclinic Acid","[structure: see text] The synthesis of the A,B,C-ring system (2) of hexacyclinic acid (1) is achieved starting from a selective Diels-Alder reaction followed by vinyl cuprate addition. The diastereoselective reduction of the ketone carbonyl at C16 could be achieved with LiAlH(4). An intramolecular Michael addition established the ring system stereoselectively, providing access to the selective generation of 9 out of the 14 stereocenters of hexacyclinic acid.",10.1021/ol048720o,2004-10-01,0.596749079232458
Journal of Organic Chemistry,2-Trimethylsilylethanesulfonyl (SES) versus Tosyl (Ts) Protecting Group in the Preparation of Nitrogen-Containing Five-Membered Rings. A Novel Route for the Synthesis of Substituted Pyrrolines and Pyrrolidines,"The 2-trimethylsilylethanesulfonyl (or SES) protecting group was compared to the tosyl (Ts) group in the preparation of a nitrogen-containing five-membered ring obtained by the aza-Baylis-Hillman/alkylation/RCM route. While deprotection of Ts-protected pyrrolines gave only pyrroles, deprotection of the same SES-protected compounds gave either pyrroles or free amine pyrrolines depending on the deprotection conditions. The SES-protected pyrrolines were hydrogenated to yield pyrrolidines with an excellent diastereoselectivity. Free amine pyrrolidines were obtained by HF-mediated deprotection of the SES group.",10.1021/jo062239p,2007-01-20,0.5967439875207617
Tetrahedron,"Pentacyclodecane chemistry. IV. Synthesis and acetolysis of - and -pentacyclo-[5.3.0.02,5.03,9.04,8]dec-6-yl tosylates. New evidence for bridged carbonium ions",,10.1016/s0040-4039(00)70345-5,1967-01-01,0.5967435132005322
European Journal of Organic Chemistry,Second‐Generation Total Synthesis of the Pigment Aurantricholone,"Abstract Our first total synthesis of aurantricholone established its benzotropolone core by the ring‐enlargement of a tetralone. Here we describe another total synthesis of aurantricholone. It reaches the benzotropolone core from a known olefin metathesis product via an equally known dibromide, both of which contain a ketoketal moiety. The next transformation ‐ step 9 overall ‐ engaged this motif in a β‐elimination of ROH rather than in a hydrolysis under the forcing acidic conditions indispensable in all prior benzotropolone preparations from such an intermediate. In step 10, the C sp 2 −Br bonds of the elimination product underwent two doubly Z ‐selective Suzuki couplings with a boronylated O ‐methyl 4‐methylidenetetronate. This gave penta( O ‐methyl)aurantricholone. Its NMR shifts matched essentially those of a derivative of natural aurantricholone by Steglich et al . Three O−Me bonds were cleaved with BBr 3 /CH 2 Cl 2 (step 11) and two O−Me bonds with LiBr/DMF (step 12). A 1 : 3 co‐crystal of aurantricholone and DMSO allowed for an X‐ray structure analysis.",10.1002/ejoc.202300648,2023-08-21,0.596740504957535
Journal of the American Chemical Society,Synthesis of a Potent Antimalarial Amphilectene,"7-Isocyano-11(20),14-epiamphilectadiene, the most potent of antimalarial amphilectenes, is synthesized in seven steps from readily available materials. The synthesis is enabled by a new dendrimeric triene (Danishefsky [3]-dendralene) and a new method for stereo- and chemoselective isocyanation. This chemistry provides a useful entry into an underexplored yet promising family of antimalarial terpenoids.",10.1021/ja310129b,2012-11-15,0.5967340921802048
Tetrahedron,A synthesis of nikkomycin Z: Improved synthesis and protection of the pyridyl γ-hydroxy-α-aminobutanoic acid component,,10.1016/s0040-4039(00)73678-1,1993-05-01,0.5967320324769474
Organic Letters,Organocatalytic Michael Addition of Indoles to Isatylidene-3-acetaldehydes: Application to the Formal Total Synthesis of (−)-Chimonanthine,"A novel strategy for the enantioselective synthesis of 3,3'-disubstituted oxindoles by the organocatalytic Michael addition of indoles to isatylidene-3-acetaldehydes was developed, which can be used for the formal total synthesis of (-)-chimonanthine and the core structure construction of (+)-gliocladin C.",10.1021/ol400845c,2013-04-25,0.5967253813337713
Tetrahedron,"Asymmetric synthesis of γ-alkayl-α-methylene-γ-butyrolactones via 1,6-remote induction using 2-[(tributylstannyl) methyl]propenamides",,10.1016/s0040-4039(00)94887-1,1985-01-01,0.5967242249331348
Journal of Organic Chemistry,"Total Synthesis of Tetarimycin A, (±)-Naphthacemycin A<sub>9</sub>, and (±)-Fasamycin A: Structure–Activity Relationship Studies against Drug-Resistant Bacteria","Making use of a reductive olefin coupling reaction and Michael–Dieckmann condensation as two key operations, we have completed a concise total synthesis of tetarimycin A, (±)-naphthacemycin A 9, and (±)-fasamycin A in a highly convergent and practical protocol. Synthetic procedures thus developed have also been applied to provide related analogues for structure–activity relationship studies, thereby coming to the conclusion that the free hydroxyl group at C-10 is essential for exerting inhibitory activities against a panel of Gram-positive bacteria, including drug-resistant strains VRE and MRSA.",10.1021/acs.joc.8b00802,2018-05-22,0.5967201752523712
Organic Letters,Asymmetric Total Synthesis of (−)-Agelastatin A Using Sulfinimine (<i>N</i>-Sulfinyl Imine) Derived Methodologies,"The asymmetric synthesis of the cytotoxic marine metabolite (-)-agelastatin A (1) has been achieved from the C-ring intermediate 4,5-diamino cyclopenten-2-enone (-)-2. This key intermediate was efficiently prepared from the sulfinimine-derived alpha,beta-diamino ester 4 using ring-closing metathesis. [reaction: see text]",10.1021/ol047634l,2005-01-20,0.5967174411675715
Tetrahedron,"Isolation and synthesis of aplysinadiene, a new rearranged dibromotyrosine derivative from aplysina aerophoba",,10.1016/s0040-4039(00)95396-6,1987-01-01,0.5967172288270147
Tetrahedron,Synthesis of novel chiral bisazetidines by the hydroalane reduction of bis-beta-lactams,,10.1016/s0040-4039(00)94772-5,1985-01-01,0.5967167947183444
Organic Letters,Synthesis of Chiral Tryptamines via a Regioselective Indole Alkylation,"A practical synthesis of chiral tryptamines from simple, unprotected indoles has been developed. Indole nucleophiles prepared with MeMgCl in the presence of CuCl reacted with chiral cyclic sulfamidates almost exclusively at the C 3 -position of indole to form a variety of α- and/or β-substituted chiral tryptamines in good yield with excellent regioselectivity. The utility of this simple alkylation process has been demonstrated with the practical synthesis of two biologically active targets, cipargamin and TIK-301, which were completed in three steps, starting from the corresponding indole starting materials.",10.1021/acs.orglett.8b02335,2018-08-21,0.5967075990654825
European Journal of Organic Chemistry,Rapid Access to the Tricyclic Core of <i>Calyciphylline A</i>‐Type Alkaloids Through Allyl Cyanate‐to‐Isocyanate Rearrangement,"Concise and efficient synthetic route to the core of calyciphylline A‐type alkaloids is described herein. The aza‐[5,6,6] tricyclic framework of the Daphniphyllum subclass of these alkaloids was constructed featuring [1,3]‐Ichikawa transposition and intramolecular Heck cyclization protocols.",10.1002/ejoc.201901549,2019-11-06,0.5967069155687181
Organic Letters,"Highly Efficient and Practical Synthesis of 3,6-Branched Oligosaccharides",[reaction: see text] A one-pot formation of the 3- and 6-OH differentially protected sugar synthon was described. A mannopyranosyl pentasaccharide and a glucopyranosyl hexasaccharide were prepared employing this new finding.,10.1021/ol000243w,2000-11-01,0.5967049113897729
Journal of Organic Chemistry,Development of Adamantan-1-yl-methoxy-Functionalized 1-Deoxynojirimycin Derivatives as Selective Inhibitors of Glucosylceramide Metabolism in Man,"In this article, we present a straightforward synthesis of adamantan-1-yl-methoxy-functionalized 1-deoxynojirimycin derivatives. The used synthetic routes are flexible and can be used to create a wide variety of lipophilic mono- and difunctionalized 1-deoxynojirimycin derivatives. The compounds reported here are lipophilic iminosugar based on lead compound 4, a potent inhibitor of the three enzymes involved in the metabolism of the glycosphingolipid glucosylceramide. Iminosugar-based inhibitors of glucosylceramide synthase, one of these three enzymes, have attracted increasing interest over the past decade due to the crucial role of this enzyme in glycosphingolipid biosynthesis. Combined with the fact that an increasing number of pathological processes are being linked to excessive glycosphingolipid levels, glucosylceramide synthase becomes a very attractive therapeutic and research target. Our results presented here demonstrate that relocating the lipophilic moiety from the nitrogen atom to other positions on the 1-deoxynojirimycin ring system does not lead to a more potent or selective inhibitor of glucosylceramide synthase. The beta-aza-C-glycoside analogue (17) retained the best inhibitory potency for glucosylceramide synthase and is a more potent inhibitor than the therapeutic agent N-butyl-1-deoxynojirimycin (3), marketed as treatment for Gaucher disease under the commercial name Zavesca.",10.1021/jo061280p,2007-01-23,0.5967046763065296
Tetrahedron,A novel route to (±)-aspidospermidine: First application of “radical-polar crossover” reactions to total synthesis,,10.1016/s0040-4039(98)80047-6,1999-01-01,0.5967028355196569
Synthesis,New One-Step Synthesis of Functionalized 2-Imidazolines,,10.1055/s-1985-31267,1985-01-01,0.5966929069292329
Journal of Organic Chemistry,Asymmetric Synthesis of a CBI-Based Cyclic <i>N</i>-Acyl <i>O</i>-Amino Phenol Duocarmycin Prodrug,"A short, asymmetric synthesis of a cyclic N-acyl O-amino phenol duocarmycin prodrug subject to reductive activation based on the simplified 1,2,9,9a-tetrahydrocyclopropa[c]benz[e]indol-4-one (CBI) DNA alkylation subunit is described. A key element of the approach entailed treatment of iodo-epoxide 7, prepared by N-alkylation of 6 with (S)-glycidal 3-nosylate, with EtMgBr at room temperature to directly provide the optically pure alcohol 8 in 78% yield (99% ee) derived from an effective metal-halogen exchange and subsequent regioselective intramolecular 6-endo-tet cyclization. Following O-debenzylation, introduction of a protected N-methylhydroxamic acid, direct trannannular spirocyclization, and subsequent stereoelectronically controlled acid-catalyzed cleavage of the resulting cyclopropane (HCl), further improvements in a unique intramolecular cyclization with N-O bond formation originally introduced for formation of the reductively labile prodrug functionality are detailed.",10.1021/jo501839x,2014-09-23,0.5966836837304411
Synlett,"Asymmetric Synthesis of Pseudo C2-Symmetric 2-Methyl Substituted 1,3-Diols","The diastereo- and enantioselective synthesis of pseudo C 2-symmetric, 2-methyl substituted, acetonide protected (4) and free 1,3-diols 5 employing the SAMP-hydrazone mothodology with virtually complete asymmetric induction (de ≥ 96%, ee ≥ 98-99%) is reported. The efficient protocol involves the asymmetric α,α""-bisalkylation of hydrazone 1, the epimerization-free Wittig olefination of the resulting ketones 2 and subsequent hydrogenation of the exo-methylene derivatives 3 with PtO2·H2O or Wilkinson's catalyst to afford the acetonide protected title compounds 4 in very good overall yields. Quantitative deprotection with trifluoroacetic acid to the free diols 5 is demonstrated.",10.1055/s-2002-19337,2002-01-01,0.596678769172276
Organic Letters,The Concise Synthesis of Unsymmetric Triarylacetonitriles via Pd-Catalyzed Sequential Arylation: A New Synthetic Approach to Tri- and Tetraarylmethanes,"The selective synthesis of multiarylated acetonitriles via sequential palladium-catalyzed arylations of chloroacetonitrile is reported. The three aryl groups are installed via a Pd-catalyzed Suzuki-Miyaura cross coupling reaction followed by back-to-back C-H arylations to afford triarylacetonitriles in three steps with no over-arylation at any step. The triarylacetonitrile products can be converted into highly functionalized species including tetraarylmethanes. This new strategy provides rapid access to a variety of unsymmetrical tri- and tetraarylmethane derivatives from simple, readily available starting materials.",10.1021/ol503213z,2014-12-19,0.5966732841942999
Tetrahedron,Synthesis of a novel diarylheptanoid isolated from Zingiber officinale,,10.1016/j.tetlet.2009.03.154,2009-03-30,0.5966659439436086
Organic Letters,Synthetic Route to Oscillatoxin D and Its Analogues,"O-Methyloscillatoxin D and its analogues were concisely synthesized by a bioinspired intramolecular Mukaiyama aldol reaction as a key step, which involves the construction of a novel spiro-ether moiety.",10.1021/acs.orglett.7b03032,2017-10-26,0.5966646144760408
Synthesis,"Synthesis of L-3,4-Didehydroproline: Favoured Orientation in the Key-Step Elimination Reaction",,10.1055/s-1982-29931,1982-01-01,0.5966620292455747
Organic Letters,"Synthesis of BILN 2061, an HCV NS3 Protease Inhibitor with Proven Antiviral Effect in Humans","The synthesis of BILN 2061, an NS3 protease inhibitor with proven antiviral effect in humans, was accomplished in a convergent manner from four building blocks. The procedure described here was suitable for the preparation of multigram quantities of BILN 2061 for preclinical pharmacological evaluation.",10.1021/ol0489907,2004-07-21,0.5966606632688112
Organic Letters,A Concise Total Synthesis of Naamidine A,"[reaction: see text]. A total synthesis of naamidine A is reported. Key benefits of the described pathway include its brevity, its synthetic ease, and its flexibility with respect to the preparation of analogues. Formation of the 2-aminoimidazole core is achieved by condensation of the appropriate alpha-aminoketone with cyanamide.",10.1021/ol052568o,2006-01-06,0.5966486138141736
Tetrahedron,An enantioselective synthesis of the A-Ring fragment of taxol,,10.1016/0040-4039(94)80125-8,1994-10-01,0.5966464719966392
Tetrahedron,An enantioselective synthesis of the A-ring fragment of taxol,,10.1016/s0040-4039(00)77379-5,1994-10-10,0.5966464719966392
Tetrahedron,Enantiopure N-acyldihydropyridones as synthetic intermediates. An asymmetric synthesis of solenopsin A,,10.1016/s0040-4039(00)75974-0,1994-01-01,0.5966353174856704
European Journal of Organic Chemistry,"Total Synthesis of (−)-4a,5-Dihydrostreptazolin","(−)-4a,5-Dihydrostreptazolin has been synthesized in nine steps from D-glyceraldehyde acetonide. Key steps include a diastereoselective addition of a vinylic Grignard reagent to an imine derived from D-glyceraldehyde acetonide, a ring-closing metathesis, and a stereoselective radical-mediated enyne cyclization.",10.1002/1099-0690(200108)2001:15<2841::aid-ejoc2841>3.0.co;2-w,2001-08-01,0.5966330672007389
Angewandte Chemie International Edition,Potent and Selective Inhibition of Acid Sphingomyelinase by Bisphosphonates,"More than mending bones: A simple geminal aminobisphosphonate (see picture) is the most potent selective inhibitor of the acid sphingomyelinase known to date. It can be synthesized in a one-step procedure and inhibits cell death in vitro. Since the acid sphingomyelinase is a putative drug target for inflammatory lung diseases, bisphosphonates may find application in the treatment of pulmonary diseases.",10.1002/anie.200903288,2009-09-10,0.5966178774683611
Tetrahedron,Synthesis of α-amino acids. Schiff base of glycine methyl ester. A new and efficient prochiral nucleophile in palladium chiral catalytic allylation.,,10.1016/s0040-4039(00)85006-6,1986-01-01,0.5966122375217277
Angewandte Chemie International Edition,Modular Synthesis of a Tridecasaccharide Motif of <i>Bacteroides vulgatus</i> Lipopolysaccharides against Inflammatory Bowel Diseases through an Orthogonal One‐Pot Glycosylation Strategy,"Lipopolysaccharides from Bacteroides vulgatus represent interesting targets for the treatment of inflammatory bowel diseases. However, efficient access to long, branched and complex lipopolysaccharides remains challenging. Herein, we report the modular synthesis of a tridecasaccharide from Bacteroides vulgates through an orthogonal one-pot glycosylation strategy based on glycosyl ortho-(1-phenylvinyl)benzoates, which avoids the issues of thioglycoside-based one-pot synthesis. Our approach also features: 1) 5,7-O-di-tert-butylsilylene-directed glycosylation for stereoselective construction of the α-Kdo linkage; 2) hydrogen-bond-mediated aglycone delivery for the stereoselective formation of β-mannosidic bonds; 3) remote anchimeric assistance for stereoselective assembly of the α-fucosyl linkage; 4) several orthogonal one-pot synthetic steps and strategic use of orthogonal protecting groups to streamline oligosaccharide assembly; 5) convergent [1+6+6] one-pot synthesis of the target.",10.1002/anie.202301351,2023-03-03,0.5966087427539863
Journal of Organic Chemistry,The Rational Synthesis of Chlorins via Rearrangement of Porphodimethenes:  Influence of β-Substituents on the Regioselectivity and Stereoselectivity of Pyrroline Ring Formation,"The porphodimethene rearrangement methodology reported in this paper provides for a rational, step-by-step synthesis of chlorins from readily available pyrrole precursors. The intermediate porphodimethenes are furnished directly via the '2 + 2' MacDonald condensation, or by the less symmetry-constrained '3 + 1' condensation of a tripyrrane and bis-formyl pyrrole. The synthetic route is short and highly convergent, especially in the case of the '3 + 1' approach, and furnishes chlorins in good to moderate yields. The synthesis is highly regioselective and appears to be based on the ability of the beta-substituent to stabilize excess electron density, with an electron-neutral hydrogen or an electron-withdrawing carbonyl beta-substituent demonstrating the greatest influence on the formation of the pyrroline ring. The synthesis is highly stereoselective when epimerization of the pyrroline ring beta-carbons is possible, furnishing only the trans-reduced sterioisomer. Finally, there is substantial evidence that a fifth, axial ligand is involved in the transposition of peripheral hydrogens during the rearrangement of the pi-system from metalloporphodimethene to metallochlorin.",10.1021/jo020105f,2002-05-25,0.5966075114618926
Angewandte Chemie International Edition,Total Synthesis of the Potent Antitumor Macrolides Pladienolide B and D,"The authors of this Communication wish to cite additional papers relevant to their work. Burkart and co-workers reported the synthesis of the undecenolide core of mycolactone by ring-closing metathesis. This synthesis of a highly functionalized 12-membered macrolide core is related to that reported by the authors. A. L. Mandel presented the synthesis of side-chain stereoisomers of pladienolide B. This synthesis is closely related to the synthetic route of the authors. The authors apologize for the unintentional oversight in not citing these two reports and wish to add these as references 5b and 7g. To establish the independence of their work to the above-mentioned reports, the authors would like to cite their patent as reference 35, to be added to the first sentence in concluding paragraph: “In conclusion, we have achieved the first total synthesis of pladienolides B (2) and D (3),35 […︁]”",10.1002/anie.200790236,2007-11-16,0.5965993973056688
Tetrahedron,Synthesis of racemic orobanchols via acid-mediated cascade cyclization: Insight into the process of BC-ring formation in strigolactone biosynthesis,,10.1016/j.tetlet.2021.153469,2021-10-13,0.5965983063279241
Organic Letters,A Convergent Coupling Strategy for the Formation of Polycyclic Ethers:  Stereoselective Synthesis of the BCDE Fragment of Brevetoxin A,"A stereoselective synthesis of the BCDE fragment of brevetoxin A has been completed. anti-Glycolate aldol, glycolate alkylation, and ring-closing metathesis reactions were employed as key bond-forming events. A convergent assembly strategy was employed that relied on a Horner-Wadsworth-Emmons union of two complex fragments. Subsequent cyclization and dehydration led to efficient generation of an intermediate endocyclic enol ether, which was advanced to a tetracyclic fragment. [reaction: see text]",10.1021/ol051543m,2005-08-09,0.5965935475869636
Tetrahedron,"Unusual conversion of substituted-3-formylchromones to 3-(5-phenyl-3H-[1,2,4]dithiazol-3-yl)chromen-4-ones: a facile and efficient route to novel 1,2,4-dithiazoles",,10.1016/j.tetlet.2007.11.081,2007-11-20,0.5965896523114292
Organic Letters,Enantioselective Synthesis of Nonfused Eight-Membered O-Heterocycles by Sequential Catalysis,"This work describes a chiral bifunctional squaramide/DBU sequential catalytic strategy for the enantioselective synthesis of nonfused chiral eight-membered O-heterocycles through the asymmetric addition of ynones to β,γ-unsaturated α-ketoesters followed by the regio- and diastereoselective cyclization of the adduct intermediates. Mechanistic experiments revealed that an isomerization process should be involved in the ring formation step, and the origin of the high regioselectivity and diastereoselectivity has also been elucidated by the DFT calculations.",10.1021/acs.orglett.4c04253,2024-12-30,0.5965875425182592
Organic Letters,Total Synthesis of Muraymycin A1: A Protecting Group Strategy for Nucleoside Antibiotic Synthesis,"Muraymycin A1 (MA1) is the most structurally complex member of its family, characterized by a 13-(1-hydroxyguanidino)tridecanoate moiety. Owing to the acid-labile hydroxyguanidino group, its chemical synthesis demands a sophisticated protecting group strategy. We accomplished the total synthesis of MA1 through highly stereoselective alkynylation and Strecker reactions, employing a (4,4'-bisfluorophenyl)methoxymethyl (BFPM)-protected uridine derivative.",10.1021/acs.orglett.5c02840,2025-08-21,0.5965851187905488
Organic Process Research & Development,Development of a Green and Sustainable Manufacturing Process for Gefapixant Citrate (MK-7264) Part 3: Development of a One-Pot Formylation–Cyclization Sequence to the Diaminopyrimidine Core,"The development of a safe, robust, and efficient manufacturing route for the synthesis of diaminopyrimidine 1, a key intermediate to gefapixant citrate (MK-7264), is described. A full mechanistic understanding of the cyclization step in the presence of guanidine was established by performing isotopic labeling experiments and identification of impurities. Guided by the mechanistic understanding, further attempts to modify the cyclization reaction by employing additives to reduce the triazine ( 9 ) formation and guanidine loading will also be presented. This newly developed method delivered compound 1 in 88–94% yield on a commercial scale and addressed the shortcomings of the early synthetic route including high PMI, low atom economy, long cycle-time, and multiple purifications to achieve the desired quality.",10.1021/acs.oprd.0c00246,2020-10-20,0.5965846340976678
Tetrahedron,Highly stereoselective palladium-catalyzed Heck coupling of 5-iodouridine-5′-triphosphates with allylamine: a new efficient method for the synthesis of (E)-5-aminoallyl-uridine-5′-triphosphates,,10.1016/j.tetlet.2012.03.018,2012-03-13,0.5965829289589338
Organic Letters,Efficient and Stereoselective Synthesis of the Disaccharide Fragment of Incednine,"Efficient and stereoselective synthesis of a disaccharide fragment, 2-deoxy-4-O-(N'-monodemethyl-D-forosaminyl)-2-methylamino-β-D-xylopyranoside, of a novel antibiotic, incednine (1), is described. The key β-stereoselective formation of a 2,3,4,6-tetradeoxy-4-methylamino glycoside bond was achieved by remote participation-assisted glycosylation.",10.1021/ol202639v,2011-10-25,0.5965801916096574
Journal of Organic Chemistry,Synthesis of Malonate-Substituted Benzocyclobutenes via Palladium-Catalyzed Alkene Difunctionalization,"The Pd-catalyzed coupling of 2-vinylphenyl triflates with malonate esters provides malonate-substituted benzocyclobutenes in moderate yield. The reactions proceed via an unprecedented intermolecular anti -nucleopalladation of the 2-vinylphenyl triflate, followed by C–C bond-forming reductive elimination to generate the strained ring. This method provides a concise, three-step route to substituted benzocyclobutenes from commercially available salicylaldehyde derivatives.",10.1021/acs.joc.5c00864,2025-06-24,0.5965716663238858
Synthesis,Novel Synthesis of a New Skeletal Compound Benzonaphthazepine by Regioselective C-H Activation Utilizing the Intramolecular Coordination of an Amine to Pd,"The novel synthesis of a new skeletal compound, benzonaphthazepine, from N-bromobenzylnaphthylamine using a Pd reagent is described. In the biaryl coupling reaction of N-bromobenzylnaphthylamine using a Pd reagent, the intramolecular coordination of the benzylamino group to Pd causes regioselective C-H activation at the peri position relative to the amine group on the naphthalene ring, producing benzonaphthazepine in good to excellent yield. The bulkiness of the substituent at C7 on the naphthalene ring affects the regioselectivity of the biaryl coupling reaction.",10.1055/s-2004-822371,2004-01-01,0.5965706666431353
Synlett,A Flow Process Using Microreactors for the Preparation of a Quinolone Derivative as a Potent 5HT1B Antagonist,"This article describes the continuous flow synthesis of 6-methoxy-8-(4-methyl-1,4-diazepan-1-yl)-N-(4-morpholinophen-yl)-4-oxo-1,4-dihydroquinoline-2-carboxamide, a potent 5HT1B antagonist developed by AstraZeneca.",10.1055/s-0029-1219358,2010-02-08,0.5965604373866612
Synlett,A Novel and Efficient Synthesis of 6-Dialkylamino-9-benzyl-8-methoxypurines and 6-Dialkylamino-9-benzylpurin-8-ones by Reaction of Methyl <i>N</i>-Benzyl-<i>N</i>-(6-dialkylamino-5-nitropyrimidin-4-yl)glycinates with Sodium Alkoxides,A novel and simple synthesis of 6-dialkylamino-9-benz­yl-8-methoxypurines and 6-dialkylamino-9-benzylpurin-8-ones by reaction of methyl N-benzyl-N-(6-dialkylamino-5-nitropyrimidin-4-yl)glycinates with sodium alkoxides is described.,10.1055/s-2006-941566,2006-05-22,0.5965598416413275
Synthesis,First Total Synthesis of 27-Deoxylyngbyabellin A,"Abstract In this study, we document the first total synthesis of the marine cyanobacteria secondary metabolite 27-deoxylyngbyabellin A in 10 linear steps with 9.7% overall yield. Key steps entailed (1) one-pot cascade reaction of (S)-2-(benzyloxy)-3-methylbutanoic acid and of Boc-l-Ile-OH with a β-azido disulfide building block to access two critical thiazole units, (2) chiral oxazaborolidinone-mediated asymmetric aldol reaction to construct an (S)-β-hydroxy ester, and (3) diphenyl phosphorazidate mediated macrolactamization of the assembled linear precursor to achieve the natural product 27-deoxylyngbyabellin A.",10.1055/a-1478-9088,2021-04-09,0.5965583688271481
Journal of Organic Chemistry,Biomimetic Synthesis of the Apoptosis-Inducing Thiazinoquinone Thiaplidiaquinone A,"A concise total synthesis of the apoptosis-inducing, marine metabolite thiaplidiaquinone A is described. The key ring forming steps are both based on biosynthetic considerations and involve the construction of the central benzo[c]chromene quinone unit by an extremely facile oxa-6π-electrocyclic ring closure reaction of an ortho-quinone intermediate, derived by tautomerization of a bis-benzoquinone, readily accessed from two simple phenolic precursors. This is followed by the installation of the 1,4-thiazine-dioxide ring by reaction of the benzo[c]chromene quinone with hypotaurine.",10.1021/jo301738u,2012-09-28,0.5965581366494015
Journal of Organic Chemistry,Redox-Neutral Dearomative Spirocyclization of Isoxazoline <i>N</i>-Oxides: A Route to Structural Analogs of Tyrosine-Derived Sponge Metabolites,A novel synthetic route to spirocyclic isoxazolines based on a redox-neutral dearomative cyclization of 3-benzyl-substituted isoxazoline N -oxides has been developed. The reaction likely proceeds through isoxazoline ring opening with generation of an unstable N -oxoiminium cation. The latter acts as an O -electrophile in the cyclization involving the ipso -position of the aryl ring. The reaction exhibits a broad substrate scope and affords spirocyclic isoxazolines featuring novel substitution patterns compared with those accessible by synthetic methods or found in natural sources.,10.1021/acs.joc.5c01669,2025-10-01,0.5965570996697047
Tetrahedron,Towards a total synthesis of the manadomanzamine alkaloids: the first asymmetric construction of the pentacyclic indole core,,10.1016/j.tetlet.2007.05.030,2007-05-11,0.5965509162140206
Journal of Organic Chemistry,"Titanium-Mediated Cyclization of ω-Vinyl Imides in Alkaloid Synthesis:  Isoretronecanol, Trachelanthamidine, 5-Epitashiromine, and Tashiromine","A new method for the stereocontrolled synthesis of pyrrolizidine and indolizidine alkaloids by means of titanium-mediated cyclization of omega-vinyl imides is described. The general procedure involves treatment of readily available omega-vinyl imides 9 and 10 with 2.5 equiv of cyclopentylmagnesium chloride in the presence of ClTi(O-i-Pr)(3) (1.1 equiv) and subsequent stereoselective reduction of the N-acylaminal group. The cis and trans ring junction stereoisomers can be stereoselectively prepared by catalytic hydrogenation (H(2), PtO(2), EtOAc) and NaCNBH(3) reduction (TFA, MeOH), respectively. Finally, treatment of the resulting lactams with LAH or diborane afforded the target alkaloids 1-8 in good yields.",10.1021/jo9907383,1999-08-11,0.596547632027487
Journal of the American Chemical Society,The Synthesis of (−)-Isodomoic Acid C,"The neuroactive algal metabolite (-)-isodomoic acid C, a kainoid amino acid, has been synthesized for the first time. Asymmetric dearomatizing cyclization of an aromatic amide using a chiral lithium amide base generates a bicyclic enone containing a pyrrolidinone ring with the relative and absolute stereochemistry of the target. A further 15 synthetic steps, including conjugate cuprate addition to the enone of a side chain precursor, a Ru-promoted oxidation of the phenyl ring to the C2-carboxylic acid substituent, a regioselective Baeyer-Villiger reaction, and an E-selective Horner-Wadsworth-Emmons reaction, elaborate the cyclization product into the target molecule.",10.1021/ja042415g,2005-02-05,0.5965464489239805
Journal of the American Chemical Society,Synthesis of the QRSTU Domain of Maitotoxin and Its 85-<i>epi</i>- and 86-<i>epi</i>-Diastereoisomers,"A devised synthetic strategy toward the QRSTU ring system 4 of the marine-derived biotoxin maitotoxin (1) delivered, in addition to 4, its diastereoisomers 85-epi-QRSTU and 86-epi-QRSTU ring systems 5 and 6. The convergent route to these maitotoxin fragments involved coupling of UT and Q building blocks 9 (obtained from 2-deoxy-D-ribose) and 10 (obtained from D-ribose) followed by ring-closing metathesis to afford enol ether 8, whose elaboration to the targeted QRSTU ring system 4 required its conversion to hydroxy ketone 7. The latter compound (7) was transformed to the final product through a hydroxy dithioketal cyclization, followed by oxidation/methylation of the resulting O,S-mixed ketal to install the last of the five methyl groups contained within the target molecule (4). (13)C NMR spectroscopic analysis of synthesized fragments 4, 5, and 6 and comparisons with maitotoxin provided strong support for the originally assigned structure of the QRSTU domain of the natural product.",10.1021/ja103708j,2010-06-25,0.5965426053941116
Tetrahedron,"Studies on the total synthesis of methyl sartortuoate construction of the 2,3,3,6-tetrasubstituted D-ring segment",,10.1016/s0040-4039(00)00608-0,2000-06-01,0.5965416812453451
Tetrahedron,"Facile Synthesis of (2S,1′S,2′S)-2-(Carboxycyclopropyl)glycine, an Isotype-Selective Agonist of Metabotropic Glutamate Receptors",,10.1016/s0040-4039(97)10037-5,1997-10-01,0.5965351682473703
Journal of the American Chemical Society,Total Synthesis and Target Identification of the Curcusone Diterpenes,"The curcusone natural products are complex diterpenes featuring a characteristic [6–7–5] tricyclic carbon skeleton similar to the daphnane and tigliane diterpenes. Among them, curcusones A–D demonstrated potent anticancer activity against a broad spectrum of human cancer cell lines. Prior to this study, no total synthesis of the curcusones was achieved and their anticancer mode of action remained unknown. Herein, we report our synthetic and chemoproteomics studies of the curcusone diterpenes which culminate in the first total synthesis of several curcusone natural products and identification of BRCA1-associated ATM activator 1 (BRAT1) as a cellular target. Our efficient synthesis is highly convergent, builds upon cheap and abundant starting materials, features a thermal [3,3]-sigmatropic rearrangement and a novel FeCl 3 -promoted cascade reaction to rapidly construct the critical cycloheptadienone core of the curcusones, and led us to complete the first total synthesis of curcusones A and B in only 9 steps, C and D in 10 steps, and dimericursone A in 12 steps. The chemical synthesis of dimericursone A from curcusones C and D provided direct evidence to support the proposed Diels–Alder dimerization and cheletropic elimination biosynthetic pathway. Using an alkyne-tagged probe molecule, BRAT1, an important but previously “undruggable” oncoprotein, was identified as a key cellular target via chemoproteomics. We further demonstrate for the first time that BRAT1 can be inhibited by curcusone D, resulting in impaired DNA damage response, reduced cancer cell migration, potentiated activity of the DNA damaging drug etoposide, and other phenotypes similar to BRAT1 knockdown.",10.1021/jacs.1c00557,2021-03-11,0.5965339495941663
Tetrahedron,"Practical enantioselective synthesis of (3S, 4R)-3-hydroxypiperidine-4-carboxylic acid",,10.1016/j.tetlet.2019.04.023,2019-04-13,0.5965206178569487
Tetrahedron,"4-hydroxymyoporone, a key intermediate in the biosynthesis of pulmonary toxins produced by infected sweet potatoes",,10.1016/s0040-4039(01)92072-6,1974-01-01,0.5965199668781916
Journal of Organic Chemistry,Synthesis of the Tetracyclic Core (ABCE Rings) of Daphenylline,"A concise synthesis of the tetracyclic core (ABCE rings) of daphenylline has been accomplished involving a benzobicyclo[3.3.1] lactam as the key intermediate. This bridged bicyclic intermediate was efficiently constructed via a Brønsted acid promoted intramolecular Friedel-Crafts type Michael addition of a δ-benzyl α,β-unsaturated δ-lactam.",10.1021/jo301533f,2012-08-30,0.596517094135071
Tetrahedron,"Heterocycle formation from 1,3-dinitroalkanes. A novel pyrazole synthesis",,10.1016/s0040-4039(00)82251-0,1988-01-01,0.5965151659573651
Journal of the American Chemical Society,Enantioselective Total Synthesis of Eunicenone A,"An enantioselective, stereocontrolled total synthesis of eunicenone A (1) is described starting from geranylgeranylacetylene (9) in 14 steps via intermediates 10-20. The most critical construction in the synthesis is the highly effective Diels-Alder combination of the achiral components 2-bromoacrolein and diene 13 in the presence of the chiral Lewis acid catalyst 14 to form 15 (85% yield, 97% ee, >98:2 endo-exo ratio). The synthesis utilizes a novel reagent (12) for introduction of silicon, which serves to activate and direct the diene 13 for Diels-Alder reaction and to provide for eventual oxygen functionality of homoallylic alcohol 17 under mild conditions. Other noteworthy steps include the position selective and diastereoselective epoxidation 17 --> 18, the methoxycarbonylation with allylic transposition 19 --> 20, and the alpha,beta-enone unmasking 20 --> 1.",10.1021/ja004043r,2001-02-10,0.5965114591029397
Organic Process Research & Development,"Dexmethylphenidate: An Efficient Process for the Racemization of Unwanted (2<i>S</i>,2′<i>S</i>or<i>l</i>-<i>threo</i>)-α-Phenyl-α-(2-piperidyl)acetamide","(2 R,2′ R )- d - threo -α-Phenyl-α-(2-piperidyl)acetamide ( 3 ), an advanced intermediate for dexmethylphenidate hydrochloride synthesis, is prepared by the resolution of dl - threo -α-phenyl-α-(2-piperidyl)acetamide ( 2 ) with dibenzoyl- d -tartaric acid in isopropanol with % yield and 99% ee. Although this process is efficient, there is a need to recycle the unwanted l - threo- amide and uncrystallized d - threo- amide from the mother liquor. The purpose of this study is 2-fold, first being the pollution issue to discard large amounts of unwanted isomer and the second to reduce the cost of ( 1 ). This aspect of recovery of unwanted isomer 4 formed the basic objective of this study. We have developed a new, simple, and cost-effective process for the racemization in which 4 was treated with potassium carbonate and N -chlorosuccinimide in DMF followed by treatment with DBU to afford the olefinic intermediate ( 5 ). Subsequent hydrogenation of the double bond provided dl - erythro -α-phenyl-α-(2-piperidyl)acetamide ( 6 ); the latter intermediate has already been converted into 1 .",10.1021/op100197g,2010-10-15,0.5965063836506684
Journal of Organic Chemistry,"An Enantioselective Access to 1-Alkyl-1,2-Dihydroisoquinolines and 1-Alkyl-, 3-Alkyl-, and 1,3-Dialkyl-1,2,3,4-tetrahydroisoquinolines","New chiral isoquinolinium salt derivatives 1, 2 or 3 have been treated with Grignard reagents to give as major products, 1-substituted 1,2-dihydroisoquinolines 4a − f, oxazolidine derivatives 10a − f or 21, respectively, in good yield and in moderate to good diastereoisomeric excess. The stereochemistry of these new derivatives has been elucidated, in particular, by X-ray crystallographic studies of 1,2-dihydroisoquinoline 4b and the minor oxazolidine 11b . Reduction of all these intermediates gave chiral 1-substituted 1,2,3,4-tetrahydroisoquinolines such as base 8 . The enantioselective synthesis of the natural alkaloid (−)-salsonidine in three steps and 38% overall yield from salt 3 is described as an application. Reduction of salt 2 gave a new oxazolidine derivative 15 which is a practical intermediate for the synthesis of 3-alkyl 1,2,3,4-tetrahydroisoquinolines 17a,b, while oxazolidines such as 10 are convenient precursors of 1,3-disubstituted tetrahydroisoquinolines, as illustrated by a synthesis of 1,3-dimethyl tetrahydroisoquinoline 20 .",10.1021/jo970768a,1998-02-24,0.5965059505369155
Tetrahedron,"A practical method for the synthesis of pyrrolizidine, indolizidine and pyrroloazepinolizidine nucleus",,10.1016/j.tetlet.2007.01.015,2007-01-08,0.59649718081789
Organic Letters,Gold(I)-Catalyzed Domino Cyclizations of Diynes for the Synthesis of Functionalized Cyclohexenone Derivatives. Total Synthesis of (−)-Gabosine H and (−)-6-<i>epi</i>-Gabosine H,"1,6-Diynes with a t-butylcarbonate group in the propargylic position undergo gold(I)-catalyzed domino-cyclization which affords α-hydroxycyclohexenones. The described sequence can be applied on functionalized, highly oxygenated substrates, as examplified in the synthesis of (-)-gabosine H and its epimer.",10.1021/acs.orglett.6b01898,2016-07-26,0.5964826894184374
Journal of Organic Chemistry,Alkoxyallene-Based Stereodivergent Syntheses of (−)-Hyacinthacine B<sub>4</sub> and of Putative Hyacinthacine C<sub>5</sub> Epimers: Proposal of Hyacinthacine C<sub>5</sub> Structure,"Hyacinthacines are members of the class of polyhydroxylated pyrrolizidines exhibiting outstanding biological activity as glycosidases inhibitors. Their structural complexity is embodied in the densely functionalized core, possessing a series of contiguous stereogenic centers. In this synthetic study we report a route to the more complex congeners of this class of alkaloids exploiting the diastereoselective addition of an axially chiral lithiated alkoxyallene to an enantiopure cyclic nitrone. Our stereodivergent approach enabled the installation of the targeted configuration at the ring A by minimal synthetic manipulations and at ring B by using stage dependent selective functionalizations. The versatility and robustness of this methodology were demonstrated by the syntheses of (−)-hyacinthacine B 4 and of two epimers of (+)-hyacinthacine C 5, allowing a suggestion of the likely structure of the isolated natural product.",10.1021/acs.joc.7b00667,2017-05-08,0.5964826471637554
Angewandte Chemie International Edition,Formal Total Synthesis of (+)‐Zaragozic Acid C through an Ireland–Claisen Rearrangement,A simple rearrangement: A formal total synthesis of zaragozic acid C (1) was achieved by the synthesis of intermediate 2. The key step involves an Ireland–Claisen rearrangement of an allylic ester to generate a carbon–carbon bond and two asymmetric centers simultaneously.,10.1002/anie.200602507,2006-08-30,0.5964790875488579
Organic Letters,Seven-Membered Ring Nucleoside Analogues: Stereoselective Synthesis and Studies on Their Conformational Properties,"The synthesis of a novel series of seven-membered ring nucleoside analogues as candidates for biological screening and gene silencing applications is described. The key step in the synthetic approach is a stereoselective synthesis of an epoxide that is used as a common synthetic intermediate to prepare functionalized oxepane nucleoside derivatives. The conformational landscape and preferred ring-puckering of selected oxepane nucleosides was also studied by NMR, X-ray crystallography, and quantum mechanical calculations.",10.1021/acs.orglett.5b02769,2015-10-22,0.5964759789905223
Organic Letters,"Synthesis, Reactivity, and Resolution of a <i>C</i><sub>2</sub>–Symmetric, P–Stereogenic Benzodiphosphetane, a Building Block for Chiral Bis(phosphines)","Although the pyramidal inversion barriers in diphosphines (R(2)P-PR(2)) are similar to those in phosphines (PR(3)), P-stereogenic chiral diphosphines have rarely been exploited as building blocks in asymmetric synthesis. The synthesis, reactivity, and resolution of the benzodiphosphetane trans-1,2-(P(t-Bu))(2)C(6)H(4) are reported. Alkylation with MeOTf followed by addition of a nucleophile gave the useful C(2)-symmetric P-stereogenic ligand BenzP* and novel analogues.",10.1021/ol301935q,2012-08-07,0.5964679332412426
Organic Letters,Total Synthesis of Amphidinolide J,"The marine natural product amphidinolide J has been synthesized according to a convergent strategy. The key steps of this synthesis include a B-alkyl Suzuki-Miyaura coupling and the addition of an alkynyllithium reagent to a Weinreb amide to build the C4-C5 and C12-C13 bonds, respectively, and a Yamaguchi macrolactonization.",10.1021/ol801708x,2008-09-24,0.5964595969926948
Synlett,Toward a New Palmerolide Assembly Strategy: Synthesis of C16-C24,"Asymmetric synthesis of C16–C24 of palmerolide A is described, featuring convergent Negishi coupling, Singaram propargylation, and successful tactical maneuvering to address an unexpected allylic substitution reaction.",10.1055/s-0031-1290675,2012-05-29,0.5964583109833484
Synlett,"Expeditious Routes to Polycyclic Molecular Frameworks via One-Pot, Two-Step Ugi Ring-Closing Sequences","A very general and robust multicomponent-reaction protocol involving an Ugi condensation between ethyl glyoxylate, isonitriles, N -Boc-α-amino acids, and mono - N -Boc-protected diamines followed by a series of acid-promoted cyclization steps in a one-pot fashion is reported. This process allows for the assembly of complex polycyclic structures by means of just two simple synthetic operations and a single chromatographic purification in high overall yields. Of note, the first scaffolds derived from a highly ­selective sequence of ring-closing events involving three internal amino nucleophiles is reported.",10.1055/s-0033-1340219,2013-11-13,0.5964537972274307
Journal of Organic Chemistry,"6-<i>s</i>-<i>cis</i> Locked Analogues of the Steroid Hormone 1α,25-Dihydroxyvitamin D<sub>3</sub>. Synthesis of Novel A-Ring Stereoisomeric 1,25-Dihydroxy-3-<i>e</i><i>pi</i>-19-<i>nor</i>-previtamin D<sub>3</sub> Derivatives","Efficient syntheses of A-ring synthons 24 and 32 are described from hydroxy ester 16, which is easily available on a preparative scale from (-)-quinic acid. Key features of the syntheses were (a) the ability to selectively perform desilylations in the presence of p-nitrobenzoate esters and (b) the excellent yield and complete stereospecificity with which the configuration of alcohols 16, 18, and 26 could be inverted under Mitsunobu conditions. Thus, A-ring synthons 24 and 32 were both prepared in 35-38% yield (eight steps) from the common precursor 16. The coupling of A-ring synthons 24 and 32 with the appropriate CD-ring/side chain fragment 7 provides access to novel 6-s-cis locked analogues of steroid hormone 1alpha, 25-dihydroxyvitamin D(3): 1alpha, 25-dihydroxy-3-epi-19-nor-previtamin D(3) (37) and 1beta, 25-dihydroxy-3-epi-19-nor-previtamin D(3) (38), which are unable to undergo rearrangement to the respective vitamin D form by virtue of the absence of the C-19 methyl group. Compounds 37 and 38 can be used as tools for studying the genomic and nongenomic mechanisms of action of the previtamin form of the hormone 1alpha, 25-dihydroxyvitamin D(3).",10.1021/jo000443l,2000-08-10,0.5964362637646872
Tetrahedron,Synthetic studies of microtubule stabilizing agent peloruside A: an asymmetric synthesis of C10C24 segment,,10.1016/j.tetlet.2003.08.023,2003-09-16,0.5964333027984111
Organic Letters,Development of a Strategy for the Total Synthesis of <i>Aspidosperma</i> Alkaloids via the Cyclobutenone-Based PET-Initiated Cationic Radical-Driven [2+2]/Retro-Mannich Reaction,A novel strategy for the synthesis of Aspidosperma alkaloids has been achieved via a photoredox-initiated [2+2]/retro-Mannich reaction of tryptamine-substituted enaminones as a key step. The developed chemistry has been applied to the construction of the core tetracycle of Aspidosperma alkaloids (±)-aspidospermidine and (±)-limaspermidine.,10.1021/acs.orglett.4c00540,2024-04-09,0.5964328405674375
Organic Letters,Highly Enantioselective Synthesis of Chiral Cyclic Amino Alcohols and Conhydrine by Ruthenium-Catalyzed Asymmetric Hydrogenation,"A highly efficient enantio- and diastereoselective synthesis of chiral cis-beta-N-alkyl/arylamino cyclic alcohols has been realized by asymmetric hydrogenation of racemic alpha-amino cyclic ketones via DKR catalyzed by [RuCl(2)((S)-Xyl-SDP)((R,R)-DPEN)]. The enantioselectivities of the reaction were up to 99.9% ee with 99:1 cis-selectivities. A practical catalytic asymmetric synthesis of all four isomers of conhydrine was also developed.",10.1021/ol901605a,2009-09-29,0.5964320101054629
Tetrahedron,Development of a practical synthesis of an antifungal drug posaconazole and the study of a critical process impurity,,10.1016/j.tetlet.2023.154574,2023-05-20,0.5964301385050372
Tetrahedron,"A new synthesis of α,β-unsaturated N-methoxy-N-methylamides",,10.1016/s0040-4039(98)01208-8,1998-08-01,0.5964284463361077
Journal of Organic Chemistry,Protecting-Group-Free Synthesis of Taiwaniaquinone H Using a One-Pot Thermal Ring Expansion/4π-Electrocyclization Strategy,"A strategy to the 6-5-6 tricyclic scaffold of taiwaniaquinoids was established on the basis of a one-pot thermal ring expansion/4π-electrocyclization process. The efficiency of this methodology has been demonstrated through its application in the total synthesis of taiwaniaquinone H, which has been accomplished in three steps and 14% overall yield in a protecting-group-free manner starting from commercially available materials.",10.1021/jo5008652,2014-05-16,0.5964230080566368
Journal of Organic Chemistry,Total Synthesis of Sialylgalactosylgloboside:  Stage-Specific Embryonic Antigen 4,"A versatile total synthesis of sialylgalactosylgloboside (SGG, 1), carrying the stage-specific embryonic antigen 4 (SSEA-4) is reported, illustrating a more general strategy for the synthesis of complex globo-series glycosphingolipids. Starting from readily available building blocks 7, 8, and 10, two different approaches to the synthesis of the key tetrasaccharide 6 have been developed in a highly convergent manner. Further glycosylations with galactosyl trichloroacetimidate (5) and sialyl phosphite (2) donors successively afforded the penta- and hexasaccharides 3 and 11. The latter was finally converted into the target molecule (SGG, 1) with the help of a azidosphingosine glycosylation procedure, favored in this case by the stereocontrolling properties of the 2a-O-pivaloyl protecting group. Valuable intermediates 6 and 3, having the oligosaccharidic skeletons of Gb(4) and Gb(5) (SSEA-3), respectively, were obtained in the course of the synthesis.",10.1021/jo9608073,1996-01-01,0.5964225944809363
Angewandte Chemie International Edition,"Total Synthesis of Thiostrepton, Part 2: Construction of the Quinaldic Acid Macrocycle and Final Stages of the Synthesis","The flagship of the thiopeptide class of antibiotics, thiostrepton (see formula), was synthesized by fusion of the quinaldic acid moiety onto the dehydropiperidine–thiazoline macrocycle (see above) followed by demasking of its sensitive functionalities.",10.1002/anie.200461341,2004-09-14,0.5964174527441889
Synthesis,Practical Synthesis of Optically Pure Menthylamines Starting from Racemic Neomenthol,A reliable and scalable route to racemic and highly enantiomerically enriched menthylamines exploits the technical product rac-neomenthol as the starting material. The elaborated protocol is based on nucleophilic substitution of the hydroxy moiety by azide. Subsequent reduction and resolution with tartaric acid provides the desired optically enriched menthylamines.,10.1055/s-0030-1258295,2010-10-13,0.5964125816290445
Organic Letters,Synthesis of the C13–C27 Fragment of Madeirolide A Using Visible-Light-Promoted Radical Cyclization,The convergent synthesis of a fully elaborated C13-C27 fragment of madeirolide A has been achieved. The key features of the synthesis include the stereocontrolled construction of both the THF and THP rings via visible-light-induced iridium-catalyzed radical cyclization and the late-stage union of the two oxacyclic subunits through nickel-catalyzed decarboxylative cross-coupling.,10.1021/acs.orglett.3c04305,2024-01-31,0.596410682559496
Tetrahedron,A convenient synthesis of phosphoenolpyruvate via silyl-ester intermediate,,10.1016/s0040-4039(01)85476-9,1980-01-01,0.5964100990592229
Tetrahedron,"Iterative Pd catalyzed additions for a synthesis of methyl 7,8,11,12 tetradehydroretionate",A 6 step synthesis of the title compound derives from a palladium catalyzed addition of terminal alkynes to acceptor alkynes.,10.1016/0040-4039(96)00726-5,1996-06-01,0.5963946882537879
Tetrahedron,"A highly facile approach to the synthesis of novel 2-(3-benzyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-1-yl)-N-phenylacetamides",,10.1016/j.tetlet.2012.11.090,2012-11-29,0.5963861985202202
Tetrahedron,A novel synthetic route for the preparation of alkyl and benzyl chloromethyl phosphates,,10.1016/s0040-4039(02)00707-4,2002-05-01,0.5963812334367694
European Journal of Organic Chemistry,"An Unprecedented Route for the Synthesis of 3,3′‐Biindoles by Reductive Cyclization of 3‐[2‐Nitro‐1‐(2‐nitrophenyl)ethyl]‐1<i>H</i>‐indoles Mediated by Iron/Acetic Acid","Abstract An unprecedented route for the synthesis of 3,3′‐biindoles is developed. Both symmetrical and unsymmetrical 3,3′‐biindoles could be generated by this method. Mild conditions, high yields of the products, and environmentally acceptable reagent are the merits of the procedure.",10.1002/ejoc.201000276,2010-06-09,0.5963733034058222
Journal of Organic Chemistry,General Strategy for the Construction of Enantiopure Pyrrolidine-Based Alkaloids. Total Synthesis of (−)-Monomorine,"An enantiopure cis-2,5-disubstituted pyrrolidine building block was prepared from cocaine. The synthetic utility of this compound as a chiral building block was demonstrated by a short and efficient synthesis of the pyrrolidine-based alkaloid (-)-monomorine (six steps, 37% overall yield).",10.1021/jo062532p,2007-03-16,0.5963672491241694
Organic Letters,Synthetic Studies on the Bryostatins:  Synthetic Routes to Analogues Containing the Tricyclic Macrolactone Core,"[reaction: see text]. Synthesis of the first of a projected series of bryostatin analogues has been accomplished in 26 steps and 2.2% overall yield. In this letter, we detail two approaches to the structural core of these tricyclic macrolactone bryostatin analogues. The key features of the route include BITIP-catalyzed asymmetric allylation reactions and Mukaiyama aldol reactions, a chelation-controlled allylation, pyran annulation reactions, and macrolactonization.",10.1021/ol050512o,2005-04-28,0.5963667946444356
Synlett,"Enantioselective Synthesis of γ,δ-Disubstituted β-Hydroxy δ-Lactones from Furans: Synthesis of (<i>+</i>)-Prelactone B and its C-4 Epimer","A new method for the enantioselective synthesis of gamma,delta-disubstituted beta-hydroxy delta-lactones (5,6-dialkyl-5,6-dihydropyran-2-ones) is reported and exemplified for (+)-prelactone B and its C-4 epimer. Our approach is based on the ring-enlargement of suitably functionalized optically pure 4-hydroxycyclopentanones, which are readily obtained from chiral 4-hydroxycyclopent-2-enones derived from furans. The procedure is amenable to the large-scale synthesis of the title compounds.",10.1055/s-2003-42057,2003-01-01,0.5963651284996889
Tetrahedron,Novel synthesis of carbohydrates using electroreduction as key reactions,,10.1016/s0040-4039(00)85717-2,1982-01-01,0.5963517459927511
Organic Process Research & Development,Development of a Robust Process for the Preparation of High-Quality Dicyclopropylamine Hydrochloride,"A short and efficient process for the preparation of high-quality dicyclopropylamine HCl salt is described. An oxygen-mediated Chan–Lam coupling of N -cyclopropyl 4-nitrobenzenesulfonamide with cyclopropylboronic acid was followed by an optimized p -nosyl deprotection with 1-decanethiol, providing the title compound in high chemical yield. This process addresses many of the challenges and liabilities inherent in previous synthetic approaches to this challenging molecule. The collection of key safety data enabled implementation of an oxygen-mediated process on-scale and ensured safe operation throughout development, optimization, and processing.",10.1021/op500031z,2014-03-11,0.59634589620947
Organic Letters,Total Synthesis of Repeating Unit of <i>O</i>-Polysaccharide of <i>Providencia alcalifaciens</i> O22 via One-Pot Glycosylation,The first total synthesis of the phosphorylated trisaccharide repeating unit of Providencia alcalifaciens O22 is reported. The trisaccharide contains rare deoxyamino sugar AAT at the reducing end and d-glyceramide 2-phosphate at the other end. The efficient synthesis involves one-pot assembly of trisaccharide and late-stage phosphorylation as key steps.,10.1021/acs.orglett.7b02791,2017-09-26,0.596345489324696
Journal of Organic Chemistry,"Synthesis and Characterization of a Highly Potent and Selective Isotopically Labeled Retinoic Acid Receptor Ligand, ALRT1550","The syntheses of two labeled homologues of (2E,4E,6E)-7-(3,5-di-tert-butylphenyl)-3-methylocta-2,4,6-trienoic acid (ALRT1550, 2), [(13)CD(3)]ALRT1550 (3) and [(3)H]ALRT1550 (4), are described in this report. ALRT1550 is an exceptionally potent antiproliferative agent which is currently in phase I/II clinical trials for acute chemotherapy. Both homologues were prepared from commercially available 3,5-di-tert-butylbenzoic acid. Homologue [(13)CD(3)]ALRT1550 was labeled at the 7-position of the trienoic acid chain via addition of [(13)CD(3)]MgI to a Weinreb amide precursor. The preparation of [(3)H]ALRT1550 utilized novel methodology to synthesize a sterically hindered and site-specific tritium-labeled tert-butyl group. Saturation binding and Scatchard analysis of this ligand at the retinoic acid receptors are also described, along with competition binding (K(i)) values for a series of known retinoids using [(3)H]ALRT1550 or [(3)H]ATRA as the labeled probes.",10.1021/jo971409i,1998-01-13,0.5963405059647636
Journal of Organic Chemistry,Asymmetric Intramolecular Carbolithiation of Achiral Substrates: Synthesis of Enantioenriched (<i>R</i>)-(+)-Cuparene and (<i>R</i>)-(+)-Herbertene,Concise syntheses of the sesquiterpenes (R)-(+)-cuparene and (R)-(+)-herbertene by asymmetric cyclization of achiral olefinic alkyllithium precursors in the presence of (-)-sparteine are reported. The quaternary stereogenic center in each product is set at the final step of the synthesis by enantioselective (er = 61:39) 5-exo ring closure.,10.1021/jo502139m,2014-10-10,0.596337509973167
Tetrahedron,"A new route to extended tetrathiafulvalenes from α-acetyl ketene-S,S-acetals",,10.1016/j.tetlet.2006.02.128,2006-03-21,0.5963255636415661
Journal of Organic Chemistry,A Rapid and Stereoselective Route to the <i>trans</i>-Hydrindane Ring System,"A short and stereoselective route to the trans-hydrindane derivative, a potential building block for the synthesis of steroidal and related molecules, was achieved by the operation of indium, tin, and ruthenium based reagents, starting from a tetrabromo norbornyl derivative.",10.1021/jo049615v,2004-07-01,0.5963251312853053
Tetrahedron,Synthesis of an exo-ditopic receptor based on calix[4]arene and catechol,,10.1016/0040-4039(96)00867-2,1996-06-01,0.5963227411561516
Journal of Organic Chemistry,"Efficient Preparation of a 1,3-Diazidocyclitol as a Versatile 2-Deoxystreptamine Precursor","A synthesis route toward 2-deoxystreptamine, a common structure in many of the clinically important aminoglycosides, is presented. Starting from p-benzoquinone and cyclopentadiene, 2-deoxystreptamine is synthesized with key steps involving Pd(0)-catalyzed rearrangement, a retro-Diels-Alder by flash vacuum thermolysis, and Yb(III)-directed regioselective epoxide opening. The obtained diazidocyclitol 17 is a suitable 2-deoxystreptamine precursor, conveniently protected for incorporation in new aminoglycoside entities.",10.1021/jo049788k,2004-06-01,0.5963208371775167
Tetrahedron,A modular approach to marine macrolide construction. 1. An enantiocontrolled route to the C1–C12 (AB) spiroacetal sector,,10.1016/s0040-4039(97)01140-4,1997-07-01,0.5963157574793863
Journal of Organic Chemistry,Efficient Synthesis of Enantiomerically Pure β<sup>2</sup>-Amino Acids via Chiral Isoxazolidinones,"We report a practical and scalable synthetic route for the preparation of alpha-substituted beta-amino acids (beta(2)-amino acids). Michael addition of a chiral hydroxylamine, derived from alpha-methylbenzylamine, to an alpha-alkylacrylate followed by cyclization gives a diastereomeric mixture of alpha-substituted isoxazolidinones. These diastereomers are separable by column chromatography. Subsequent hydrogenation of the purified isoxazolidinones followed by Fmoc protection affords enantiomerically pure Fmoc-beta(2)-amino acids, which are useful for beta-peptide synthesis. This route provides access to both enantiomers of a protected beta(2)-amino acid.",10.1021/jo026738b,2003-01-11,0.5963116425910344
Journal of Organic Chemistry,Regioselective Quinazolinone-Directed Ortho Lithiation of Quinazolinoylquinoline:  Practical Synthesis of Naturally Occurring Human DNA Topoisomerase I Poison Luotonin A and Luotonins B and E,"A regioselective quinazolinone-directed ortho lithiation on an adjacent quinoline moiety has been used as a key step for a short, efficient, and practical synthesis of the human DNA topoisomerase I poison luotonin A and luotonins B and E. The quinazolinoylquinoline 5 on treatment with in situ-generated nonnucleophilic mesityllithium furnished the desired dilithiated intermediate 6, which on treatment with formaldehyde followed by Mitsunobu ring closure reaction gave luotonin A (1a) in very good yield. The reaction of dilithiated intermediate 6 with DMF directly furnished luotonin B (1b) in 81% yield. Luotonin B (1b) on methylation with p-TSA/methanol gave luotonin E (1c) in 82% yield.",10.1021/jo040153v,2004-06-01,0.5963100926865953
Tetrahedron,Efficient synthesis of protected 3′-deoxyadenosine and 3′-deoxyguanosine from adenosine and guanosine,,10.1016/s0040-4039(00)02041-4,2001-01-01,0.5963053187685424
Synthesis,"An Efficient Synthesis of 4-Chloro-2-pyrrolino[2,3-d]pyrimidin-6-one and Its 7-Substituted Analogues","An efficient synthesis of 4-chloro-2-pyrrolino[2,3- d ]pyrimidin-6-one was achieved in four steps starting from dimethyl malonate in 23% overall yield. This synthesis was demonstrated on 100 g scale to obtain 4-chloro-2-pyrrolino[2,3- d ]pyrimidin-6-one in 98.5% purity. Similarly, 7-[(2,4-dimethoxyphenyl)methyl]-4-chloro[2,3- d ]pyrimidin-6-one and 7-(α-methylbenzyl)-4-chloro[2,3- d ]pyrimidin-6-one were synthesized by the reaction of methyl 2-(4,6-dichloropyrimidin-5-yl)acetate with an appropriately substituted benzylamine.",10.1055/s-0031-1290408,2012-06-18,0.5963037038100952
Journal of Organic Chemistry,Synthesis of 2-Substituted Indoles and Indolines via Suzuki−Miyaura Coupling/5-<i>endo</i>-<i>trig</i> Cyclization Strategies,"New strategies for the synthesis of 2-substituted indoles and indolines using acyclic, imide-derived enol phosphates, which were readily prepared from o-haloanilides, have been developed based on Suzuki-Miyaura coupling-cyclization sequences. A highly chemoselective cross-coupling of imide-derived enol phosphates with boron nucleophiles under Suzuki-Miyaura conditions allowed for the efficient preparation of various N-(o-halophenyl)enecarbamates that served as useful precursors for subsequent 5-endo-trig Heck or 5-endo-trig aryl radical cyclizations to furnish 2-substituted indoles or indolines, respectively. Furthermore, a one-pot Suzuki-Miyaura coupling-cyclization cascade starting from enol phosphates has been developed, which was successfully applied to the efficient synthesis of an indol-2-yl-1H-quinolin-2-one KDR inhibitor.",10.1021/jo801985a,2008-11-13,0.5963034369038194
Journal of Organic Chemistry,"Diastereoselective Synthesis of a Highly Functionalized Angularly Substituted <i>cis</i>-Perhydroisoquinoline-3,6-dione via Organoiron",Nitrile addition to cyclohexadienyium-Fe(CO)(3) perchlorate salt provides an efficient entry into the angularly substituted cis-fused perhydroisoquinoline ring system. The key steps in the assembly of the angularly substituted cis-octahydroisoquinoline ring are the transformation of the nitrile to an N-(benzylmethylencie)amino group and a diastereoselective intramolecular Michael reaction to form the bicyclic ring.,10.1021/jo902605w,2010-01-29,0.5963008049718651
Tetrahedron,A single-step synthesis of (±)-α-cuparenone,,10.1016/s0040-4039(01)85433-2,1978-01-01,0.5962999738695218
Tetrahedron,Single step synthesis of an ethynylferrocenyl-[4]-ferrocenophane,,10.1016/j.tetlet.2015.06.001,2015-06-06,0.5962999738695218
Organic Process Research & Development,Chemoenzymatic Synthesis of <i>N</i>-Trifluoroacetyl Doxorubicin-14-Valerate (Valrubicin),"An efficient two-step, chemoenzymatic synthesis of N -trifluoroacetyl doxorubicin-14-valerate (Valrubicin) from doxorubicin hydrochloride salt is reported. The key step is a lipase-catalyzed regioselective esterification of N -trifluoroacetyl doxorubicin using commercially available valeric acid as the acyl donor. The overall yield for the process is 79%.",10.1021/op0501186,2005-10-20,0.5962875203658229
Synthesis,"An Improved Synthesis of Some Highly Substituted Phenols - The Prelog Condensation with 2,4,6-Heptanetrione",,10.1055/s-1980-29180,1980-01-01,0.596284060175474
European Journal of Organic Chemistry,"Synthesis of Diospyrin, a Potential Agent Against Leishmaniasis and Related Parasitic Protozoan Diseases","The first synthesis of diospyrin [2,6′-bis(5-hydroxy-7-methyl-1,4-naphthoquinone), 1] was achieved by employing Suzuki coupling between 5 and 14 as the key reaction to connect the two 7-methyljuglone units.",10.1002/1099-0690(200004)2000:7<1313::aid-ejoc1313>3.0.co;2-i,2000-04-01,0.5962783009001225
Tetrahedron,Rhodium-catalyzed carbonylation of 2-alkynylbenzylamine: a new route to the synthesis of benzazepinones,,10.1016/j.tetlet.2004.02.122,2004-03-13,0.5962757062562459
Organic Letters,Total Synthesis of (±)-Streptoglyceride A and of Putative (±)-Streptoglyceride C,"The first total synthesis of (±)-Streptoglyceride A─one of the early members of this family to be isolated─has been accomplished, along with the synthesis of the putative structure of (±)-Streptoglyceride C. The unique tricyclic ring present in these natural products has been constructed by employing a gold-catalyzed tandem diynol cycloisomerization followed by one-pot dihydroxylation/trans-glycosylation. The pendant diene unit was fabricated by Takai olefination and subsequent Stille coupling.",10.1021/acs.orglett.5c00879,2025-06-04,0.59627400733983
Tetrahedron,Synthesis of quinolines from the Baylis–Hillman acetates via the oxidative cyclization of sulfonamidyl radical as the key step,,10.1016/s0040-4039(02)01314-x,2002-08-01,0.5962730566295564
Journal of Organic Chemistry,"Synthesis and Cytotoxicity of 5-Amino-1-(chloromethyl)-3-[(5,6,7-trimethoxyindol-2-yl)carbonyl]-1,2- dihydro-3<i>H</i>-benz[<i>e</i>]indole (Amino-<i>s</i><i>eco</i>-CBI-TMI) and Related 5-Alkylamino Analogues:  New DNA Minor Groove Alkylating Agents","The first synthesis of seco -CBI-TMI alkylating agents with 5-nitrogen substituents is reported. The parent 5-amino compound was prepared in a 15-step synthesis from 1-hydroxynaphthalene-2-carboxylic acid. Reductive alkylation of the 5-amino compound gave the corresponding 5-methylamino and 5-dimethylamino analogues, while resolution of an intermediate by chiral HPLC allowed preparation of the R and S enantiomers of the 5-amino analogue. Absolute configuration was assigned by X-ray crystallography. The S enantiomer was about 65-fold more cytotoxic than the R enantiomer in cell line assays. The 5-amino and 5-methylamino compounds had in vitro cytotoxicities comparable to that of the known 5-hydroxy analogue (0.2−0.5 nM), while the 5-dimethylamino derivative was about 10-fold less potent. The high potencies of the 5-amino and 5-methylamino analogues make them of interest for the formation of relatively stable amine-based prodrugs.",10.1021/jo981395w,1998-11-20,0.5962698384958677
Journal of Organic Chemistry,Diastereoselective Flexible Synthesis of Carbocyclic C-Nucleosides,"Carbocyclic C-nucleosides are quite rare. Our route enables flexible preparation of three classes of these nucleoside analogs from common precursors-properly substituted cyclopentanones, which can be prepared racemic (in six steps) or optically pure (in ten steps) from inexpensive norbornadiene. The methodology allows flexible manipulation of individual positions around the cyclopentane ring, namely highly diastereoselective installation of carbo- and heterocyclic substituents at position 1', orthogonal functionalization of position 5', and efficient inversion of stereochemistry at position 2'. Newly prepared carbocyclic C-analog of tubercidine, profiled in MCF7 (breast cancer) and HFF1 (human foreskin fibroblasts) cell cultures, is less potent than tubercidine itself, but more selectively toxic toward the tumorigenic cells.",10.1021/acs.joc.6b02594,2017-03-07,0.5962684826440008
Organic Process Research & Development,"Crystallization-Induced Dynamic Resolution toward the Synthesis of (<i>S</i>)-7-Amino-5<i>H</i>,7<i>H</i>-dibenzo[<i>b</i>,<i>d</i>]-azepin-6-one: An Important Scaffold for γ-Secretase Inhibitors","An enantioselective synthesis of ( S )-7-amino-5 H,7 H -dibenzo[ b, d ]azepin-6-one ( S - 1 ) is described. The key step in the sequence involved crystallization-induced dynamic resolution (CIDR) of compound 7 using Boc- d -phenylalanine as a chiral resolving agent and 3,5-dichlorosalicylaldehyde as a racemization catalyst to afford S - 1 in 81% overall yield with 98.5% enantiomeric excess.",10.1021/acs.oprd.6b00207,2016-09-28,0.5962666820405079
Synlett,Enantioselective Synthesis of (–)-Pentazocine and (–)-Metazocine,"We have accomplished an efficient asymmetric synthesis of (–)-pentazocine and (–)-metazocine from the readily available d -tyrosine, featuring a ring-closing metathesis (RCM) reaction for the formation of the C ring and an intramolecular Friedel–Crafts reaction for the assembly of the B ring. The new strategy established herein should be applicable to enantioselective synthesis of a broad range of chiral benzomorphan analogues, thereby facilitating the biological and medicinal chemistry studies of these clinically important molecules.",10.1055/s-0035-1561501,2016-01-05,0.5962666791812778
Tetrahedron,Intramolecular Diels-Alder route to 6-oxodecahydroisoquinoline-3-carboxylates: Intermediates for the synthesis of conformationally constrained excitatory amino acid antagonists,,10.1016/s0040-4039(00)78176-7,1994-08-01,0.5962616396035663
Organic Process Research & Development,"A Facile, One-Pot Synthesis of Lacidipine Using in Situ Generation of Wittig Intermediates","An improved, one-pot process for the preparation of lacidipine ( 1 ) via an efficient in situ generation of Wittig intermediates is reported. Generation of ylide ( 4 ) by dehydrobromination of phosphonium salt ( 3 ) followed by in situ condensation of 4 with o- phthalaldehyde ( 5 ) to yield corresponding olefin ( 6 ) and its subsequent reaction with crotonate derivative ( 7 ) in the same pot furnished the drug substance 1 with an overall yield of about 51% over the reported yield of about 24% starting from the corresponding ylide. The present work overcomes the challenges associated with prior art processes such as chromatographic purifications, handling of unstable intermediates, and formation of byproducts as potential impurities. The interesting insights on the safety aspects of the process, drawn through calorimetric studies, rendered the successful implementation of the process at manufacturing facility.",10.1021/op900055u,2009-05-19,0.5962606282374795
Synlett,Efficient Asymmetric Synthesisof Oseltamivir from <scp>d</scp>-Mannitol,"A highly practical asymmetric synthesis of oseltamivir has been accomplished in 18 steps from d-mannitol without any chromatographic purification, which features intramolecular aldol condensation of dialdehyde with a 3-pentyl ether moiety in constructing densely functionalized cyclohexene ring of oseltamivir.",10.1055/s-0028-1087941,2009-02-25,0.5962376522463415
Journal of Organic Chemistry,"Electrophilic mercuration reactions of derivatives of deuteroporphyrin IX: new syntheses of coproporphyrin III, harderoporphyrin, isoharderoporphyrin, and S-411 porphyrin (dehydrocoproporphyrin)","Treatment of copper(II) deuteroporphyrin IX dimethyl ester (17) with mercuric acetate affords a peripherally metalated species in which the 2- and 4-positions are mercurated. Acidic deuterolysis and sodium borodeuteride reduction suggest that some mercury also becomes attached to the α and β meso positions. Treatment of the dimercurated material with methyl acrylate and LiPdCl3 gives the corresponding diacrylate, 8, which can be hydrogenated to afford coproporphyrin III tetramethyl ester (7). Mercuration of copper(II) monoacetyldeuteroporphyrins IX 15 and 16 can also be readily accomplished, and in this way a new synthetic route to harderoporphyrin and isoharderoporphyrin trimethyl esters (14 and 24, respectively) is developed. A novel method for deacetylation of copper(II) porphyrins is described, and along with the mercuration/olefin coupling reaction, this is employed in a new synthesis of the S-411 porphyrin (dehydrocoproporphyrin) obtained from meconium, as its tetramethyl ester, 34. © 1983, American Chemical Society. All rights reserved.",10.1021/jo00152a018,1983-02-01,0.5962376514817439
Synthesis,"Practical and Efficient Synthesis of a Chiral C<sub>5</sub> Building Block, 2-<i>O</i>-Allyl-<scp>d</scp>-arabinose, from Diacetone-<scp>d</scp>-glucose","The first syntheses of a 2-O-allylpentose are described. Starting from d-arabinose (2), 2-O-allyl-d-arabinose (1) was obtained in 36-42% yield over five steps. A practical and efficient synthesis from cheap and abundant diacetone glucose yielded 56% of 1 over only three steps.",10.1055/s-2006-926418,2006-04-25,0.5962319428930114
Tetrahedron,Synthesis of polyfunctionalized benzo[ d ]thiazoles as novel anthranilic acid derivatives,,10.1016/j.tetlet.2015.05.018,2015-05-11,0.5962269722363441
Angewandte Chemie International Edition,A Short Total Synthesis of Kuehneromycin A,"Only eleven steps were needed to synthesize kuehneromycin A (1) which inhibits reverse transcriptase (see picture). Key steps are a new variant of the Baylis–Hillman reaction, an endo-selective intramolecular Diels–Alder reaction, and a new protocol for the Parikh–Doering oxidation. TBDPS=tert-butyldiphenylsilyl.",10.1002/1521-3773(20000804)39:15<2764::aid-anie2764>3.0.co;2-s,2000-08-04,0.5962174329276608
Tetrahedron,Three-membered ring formation reaction [II] asymmetric synthesis of the cyclopropanedicarboxylic acid ester from methyl α-chloroacrylate with ethylzinc chloride,,10.1016/s0040-4039(01)96752-8,1971-01-01,0.5962131945006096
Tetrahedron,"A new route to BCD tricyclic fragment of C19-diterpenoid alkaloids via intramolecular Pauson-Khand reaction followed by anionic 1,2-migration rearrangement",,10.1016/j.tetlet.2021.152975,2021-03-06,0.5962121220417528
Synthesis,Enantioselective Synthesis of (+)-Sedamine and (-)-Allosedamine,"Two different approaches to the enantioselective syntheses of (+)-sedamine and (-)-allosedamine are described, both using the Sharpless asymmetric epoxidation as the key step. Regioselective reduction of epoxides, chemoselective oxidation of alcohols, ring-closing metathesis, and nucleophilic displacements were the other key steps employed.",10.1055/s-2006-950331,2006-12-01,0.596210428618725
Angewandte Chemie International Edition,α‐Oxygenated Crotyltitanium and Dyotropic Rearrangement in the Total Synthesis of Discodermolide,"A complete strategy: The total synthesis of discodermolide relies on the elaboration of syn–anti stereotriads linked to a Z-O-enecarbamate group, its direct transformation into the terminal Z diene, and stereocontrolled generation of the trisubstituted Z double bond by a dyotropic rearrangement (see scheme; OCb=N,N-diisopropylcarbamoyloxy). The synthesis was achieved in 21 steps with 1.6 % overall yield.",10.1002/anie.200604629,2007-02-02,0.5962041232505519
Tetrahedron,Synthesis of an analogue of lavendamycin and of conformationally restricted derivatives by cyclization via a hemiaminal intermediate,,10.1016/j.tetlet.2007.06.100,2007-06-26,0.5962020994874828
Tetrahedron,An easy route to pentacyclic terpenylquinones,,10.1016/j.tetlet.2011.11.080,2011-11-23,0.5961994749882172
Synlett,An Easy Route from Catechols to Phthalonitriles,,10.1055/s-1998-1914,1998-11-01,0.5961994749882172
Journal of Organic Chemistry,Grignard Addition to Aldonitrones. Stereochemical Aspects and Application to the Synthesis of C<sub>2</sub>-Symmetric Diamino Alcohols and Diamino Diols,"A new example of the stereoselective installation of the amino group at a saturated carbon center via organometallic addition of chiral aldehydes to nitrones is illustrated by the synthesis of 1,3-diamino propanol 1 and 1,4-diamino butandiol 2 units. Three diamino alcohol 1 stereotriads were obtained by stereoselective addition of alkylmagnesium halides (benzyl, cyclohexylmethyl, and metallyl) to the N -benzyl nitrones derived from β-amino-α-hydroxy aldehydes followed by reduction of the resulting N -benzylhydroxylamines. Three 1,4-dibenzyl substituted stereoisomers of type 2 with fixed S configuration at C2 and C3 were prepared by sequential and simultaneous amination in two directions starting from l -threose nitrone and l -tartraldehyde bis-nitrone, respectively. The R, S, S, R isomer obtained by the former route was converted into a seven-membered ring cyclic urea (1,3-diazapin-2-one), i.e., a compound that belongs to a class of nonpeptide HIV-1 protease inhibitors.",10.1021/jo980980u,1998-11-20,0.5961976540227663
Tetrahedron,A new route to seven-and eight-membered carbocycles,,10.1016/s0040-4039(97)01142-8,1997-07-01,0.5961970523136668
Organic Letters,Total Synthesis of Caerulomycin C via the Halogen Dance Reaction,"[reaction: see text] The total synthesis of caerulomycin C is described. Key steps in this synthesis utilize 1,2-, 1,3-, and 1,4-halogen dance reactions for the functionalization of the pyridine ring.",10.1021/ol026135m,2002-06-19,0.5961888516343409
Journal of Organic Chemistry,Construction of Pentacyclic Lamellarin Skeleton via Grob Reaction: Application to Total Synthesis of Lamellarins H and D,"An efficient construction of phenyl-substituted coumarin-pyrrole-isoquinoline-fused pentacycle via base-promoted Grob-type coupling of 3-nitrocoumarin and papaverine in a sealed tube is reported. This reaction is further applied to the total synthesis of lamellarin H in three linear steps and lamellarin D in eight linear steps with overall yields of 31% and 14%, respectively.",10.1021/acs.joc.7b01061,2017-06-22,0.5961792403790298
Journal of Organic Chemistry,Synthesis and Structural Implication of the JKLMN-Ring Fragment of Caribbean Ciguatoxin C-CTX-1,"Synthesis of the JKLMN-ring fragment of Caribbean ciguatoxin C-CTX-1, the causative toxin of ciguatera fish poisoning in the Caribbean Sea and the Northeast Atlantic areas, is described in detail. Key to the synthesis are a [2,3]-sigmatropic rearrangement to construct a seven-membered α-hydroxy exo -enol ether, stereoselective construction of an angular tetrasubstituted stereogenic center on the seven-membered M-ring by a hydrogen atom transfer-based reductive olefin coupling, Suzuki–Miyaura coupling of the KLMN-ring enol phosphate with a highly congested M-ring, and silica gel-mediated epoxide ring opening to form the J-ring. Comparison of the nuclear magnetic resonance spectroscopic data for the synthesized fragment with those for the natural product provided support for the formerly assigned structure of the N-ring in the right-hand terminal of C-CTX-1.",10.1021/acs.joc.0c03031,2021-03-05,0.5961744842122825
Tetrahedron,Total synthesis of diospyrol an anthelmintic drug from diospyros mollis griff,,10.1016/s0040-4039(01)80678-x,1989-01-01,0.5961744029131493
Angewandte Chemie International Edition,"Ring‐Contraction Strategy for the Practical, Scalable, Catalytic Asymmetric Synthesis of Versatile γ‐Quaternary Acylcyclopentenes",Contraction action! A simple protocol for the catalytic asymmetric synthesis of highly functionalized γ-quaternary acylcyclopentenes (see schematic) in up to 91 % overall yield and 92 % ee has been developed. The reaction sequence employs a palladium-catalyzed enantioselective alkylation reaction and exploits the unusual stability of β-hydroxy cycloheptanones to achieve a general and robust method for performing two-carbon ring contractions.,10.1002/anie.201007814,2011-02-24,0.5961742251773089
Tetrahedron,A highly efficient route to taxotere by the β-Lactam Synthon Method,,10.1016/s0040-4039(00)60514-2,1993-06-01,0.5961711992977908
Angewandte Chemie International Edition,Wavelength‐Gated Photochemical Synthesis of Phenalene Diimides,"Herein, we pioneer a wavelength-gated synthesis route to phenalene diimides. Consecutive Diels-Alder reactions of methylisophthalaldehydes and maleimides afford hexahydro-phenalene-1,6-diol diimides via 5-formyl-hexahydro-benzo[f]isoindoles as the intermediate. Both photoreactions are efficient (82-99 % yield) and exhibit excellent diastereoselectivity (62-98 % d.r.). The wavelength-gated nature of the stepwise reaction enables the modular construction of phenalene diimide scaffolds by choice of substrate and wavelength. Importantly, this synthetic methodology opens a facile avenue to a new class of persistent phenalenyl diimide neutral radicals, constituting a versatile route to spin-active molecules.",10.1002/anie.202016632,2021-02-11,0.5961530435879818
Tetrahedron,A novel approach to iboga alkaloids: Total synthesis of (±)-ibogamine and (±)-epi-ibogamine,,10.1016/0040-4039(96)01939-9,1996-11-01,0.5961491786105413
Synthesis,Synthesis of Bempedoic Acid through Electrochemical Decarboxylation of Dialkylated Malonic Acid,"Abstract Bempedoic acid is a small-molecule inhibitor of adenosine triphosphate-citrate lyase (ACL) that is effective in the treatment of hypercholesterolemia and hypertension. In this paper, a new, six-step synthesis of bempedoic acid with 42% overall yield is reported. Ketone formation by electrochemical decarboxylation of dialkylated malonic acid is introduced as the key step of this process. This method uses mild conditions and its high efficiency makes it potentially suitable for industrial production.",10.1055/a-1482-9822,2021-04-15,0.5961449878868023
Synthesis,"A Synthesis of Jaspamide Based on 1,2-Metallate Rearrangements of α-Heteroalkenylmetal Derivatives","All articles of this category Jaspamide (Jasplakinolide), a marine cyclodepsipeptide, was synthesised from tripeptide fragment 4 and (2 S ,4 E ,6 R ,8 S )-8-benzoyloxy-2,4,6-trimethylnon-4-enoic acid (3) . The tripeptide fragment was prepared from β -tyrosine derivative 6 , Boc-2-bromoabrine (8) , and alanine. β -Tyrosine derivative 6 was prepared by asymmetric conjugate amination of methyl p -hydroxycinnamate. Bromabrine derivative 8 was prepared from tryptophan. Key steps in the synthesis of the polyketide fragment 3 include 1,2-metallate rearrangement of a metallated dihydropyran and a metallated enol carbamate derivative. cyclodepsipeptide - Jaspamide - antifungal - 1,2-metallate rearrangement - higher order cuprate - enol carbamate",10.1055/s-1995-3870,1995-02-01,0.5961427098978903
Tetrahedron,Asymmetric dihydroxylation and hydrogenation approaches to the enantioselective synthesis of R-(+)-α-lipoic acid,,10.1016/s0040-4039(01)00734-1,2001-07-01,0.5961346673766443
Organic Letters,A Formal Approach to Xylosmin and Flacourtosides E and F: Chemoenzymatic Total Synthesis of the Hydroxylated Cyclohexenone Carboxylic Acid Moiety of Xylosmin,"The hydroxylated cyclohexenone carboxylic acid moiety of xylosmin was synthesized in eight steps from benzoic acid. The key steps in the synthesis involved the enzymatic dihydroxylation of benzoic acid by the whole cell fermentation with Ralstonia eutrophus B9, and Henbest epoxidation. Early attempts led to the synthesis of a C6 epimer of the methyl ester of the hydroxylated cyclohexenone carboxylic acid moiety. The absolute stereochemistry of an advanced intermediate was confirmed by X-ray crystallography. Complete characterization of the previously reported but not fully characterized hydroxylated cyclohexenone carboxylic acid is provided.",10.1021/acs.orglett.7b00194,2017-02-10,0.596133670782189
Synthesis,An Improved Method for the Synthesis of 3-Fluorosalicylic Acid with Application to the Synthesis of 3-(Trifluoromethyl)salicylic Acid,,10.1055/s-1999-3607,1999-11-01,0.5961288276514095
Organic Process Research & Development,An Expeditious Scalable Synthesis of (<i>S</i>)-2-Amino-5-methoxytetralin via Resolution,"The first resolution of (±)-2-amino-5-methoxytetralin 1 is achieved via diastereomeric salt formation with ( S )-mandelic acid to give ( S )- 1 ·HCl of 99.7% ee in 29% overall yield from (±)- 1 ·HCl, ( S )- 1 ·HCl being a chiral intermediate to assemble N-0923 2, a potent dopamine D 2 agonist effective against Parkinson's disease. Preparation of (±)- 1 ·HCl involves the Birch reduction of 1,6-dimethoxynaphthalene 3b and reductive amination of 5-methoxy-2-tetralone 4 with aqueous NH 3 over Raney Ni under a hydrogen atmosphere (2.9−3.9 bar) between 70 and 80 °C. With the off-enantiomer ( R )- 1 arising from the resolution, its xylene solution is heated at 130 °C over Raney Co under a hydrogen atmosphere (2.0−2.7 bar) to regenerate (±)- 1 ·HCl in 95% yield, which should enhance the overall throughput of the resolution process.",10.1021/op0498363,2004-12-02,0.5961268465597299
Angewandte Chemie International Edition,Nickel and Palladium Catalysis in the Stereoselective Synthesis of Functionalized Pyrrolidines: Enantioselective Formal Synthesis of (+)-α-Allokainic Acid,"Neuroexcitatory natural products are accessible from 1 via the intermediate 2, which is obtained by Ni-catalyzed cyclization, transposition of the protecting group, and Pd-catalyzed reduction with allylic transposition. This stepwise formation of stereocenters allows a highly direct and stereoselective synthesis of the excitatory amino acid (+)-α-allokainic acid, which displays an all-trans arrangement of the substituents about the pyrrolidine ring. TBS=tert-butyldimethylsilyl.",10.1002/(sici)1521-3773(19981204)37:22<3144::aid-anie3144>3.0.co;2-y,1998-12-04,0.5961260565157022
Organic Letters,Synthesis of Microcin SF608 through Nucleophilic Opening of an Oxabicyclo[2.2.1]heptane,The total synthesis of Microcin SF608 is reported. Access to the octahydroindole core structure of Microcin SF608 relies on the TMSOTf/NEt(3)-mediated opening of an oxabicyclic ring system. Additional highlights of the synthetic strategy that is reported include a highly regioselective epoxide reduction and photolytic excision of a 3 degrees alcohol.,10.1021/ol1017189,2010-08-12,0.5961255956075968
Angewandte Chemie International Edition,Highly Diastereoselective Alkylation of Aziridine‐2‐carboxylate Esters: Enantioselective Synthesis of LFA‐1 Antagonist BIRT‐377,The benzhydryl group is the key: Efficient alkylation of 3-substituted aziridine-2-carboxylates is only possible with N-benzhydryl-protected aziridines and occurs with complete retention of the configuration at the 2-position. Sequential catalytic asymmetric aziridination and aziridine alkylation reactions have been applied to the synthesis of BIRT-377 (see structure).,10.1002/anie.200500923,2005-08-24,0.5961194823411858
Journal of Organic Chemistry,Formal Total Syntheses of the (−)-Salicylihalamides A and B From <scp>d</scp>-Glucose and <scp>l</scp>-Rhamnose,"[reaction: see text] Two formal total syntheses of the (-)-salicylihalamides, based on chiral pool approaches, are reported. D-glucose and L-rhamnose were used to prepare advanced intermediates 23 and 54, which can be converted in three or four steps, respectively, to the target compounds. The synthesis of 23 from a known D-glucose-derivative was accomplished in 12 steps and 17% overall yield, and the synthesis of 54 from a known L-rhamnose-derivative was done in nine steps and 6% overall yield. A key step in the synthesis was a ring-closing metathesis reaction to prepare the macrocyclic ring system. It was demonstrated that the phenolic protecting group was critical for inducing the preferential formation of the desired E isomer. It was further shown that the protecting group at the C13 hydroxyl group had no significant influence on the E:Z ratio during the ring-closing metathesis reaction.",10.1021/jo050750x,2005-08-12,0.5961083913230841
European Journal of Organic Chemistry,Enantiospecific Synthesis of (+)‐Hyacinthacine A<sub>2</sub>,"Abstract We report an efficient synthesis of (+)‐hyacinthacine A 2 in six steps from ( S )‐ N ‐Cbz‐vinylgylcine. The key strategies were the olefin cross metathesis (CM), Sharpless asymmetric dihydroxylation, and a sequential double reductive cyclization. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2006)",10.1002/ejoc.200500914,2006-02-21,0.5961083140660256
Organic Process Research & Development,Concise Large-Scale Synthesis of the Highly Active Cephalosporin Cefdaloxime,"Cefdaloxime ( 1a ) is the bioactive principle of the 1-( S )-(pivaloyloxy)ethyl ester prodrug HR916K ( 1b ). To provide material for biological investigations a short and efficient large-scale synthesis of 1a was developed, which avoids chromatographic purification steps. Commercially available (6 R,7 R )-7-amino-3-(methoxymethyl)-3-cephem-4-carboxylic acid (AMCA) ( 2 ) is acylated with trityl-protected mercaptobenzothiazole thioester in the presence of bis(trimethylsilyl)acetamide to yield tritylated cefdaloxime. The trityl group is then removed by treatment with formic acid, followed by pH-adjusted precipitation of 1a . For a final purification, which has to consider cefdaloxime specific side reactions, crude 1a is dissolved in dimethyl sulfoxide and precipitated with methanol to obtain 1a in 66% overall yield on a kilogram scale.",10.1021/op960025b,1997-03-01,0.5961055639822782
European Journal of Organic Chemistry,"Divergent Synthetic Route to Oxidized Benzofulvene Sesquiterpenoids: Protecting‐Group‐Free Total Synthesis of Nicotianasesterpenes A, B, and a Polygonum Sesquiterpenoid","A divergent approach toward the protecting‐group‐free total synthesis of oxidized benzofulvene sesquiterpenoids is described. Highlight of our synthesis includes regio‐ and stereoselective assembly of the common intermediate 9 by the orchestrated application of a Pd(0)‐catalyzed reductive dehalogenation, a solvent‐free methylenation, and a vinylogous Stork enamine aldol condensation in a substrate‐controlled manner. The advanced intermediate 9 was efficiently transformed to nicotianasesterpenes A, B, and a polygonum sesquiterpenoid, respectively.",10.1002/ejoc.201901351,2019-09-18,0.5960951829691656
Organic Process Research & Development,"The Discovery and Process Development of a Commercial Route to the Water Soluble Prodrug, Fosfluconazole","A case history detailing the rationale behind the discovery of 2-(2,4-difluorophenyl)-1,3-bis(1 H -1,2,4-triazole-1-yl)-2-propyl dihydrogen phosphate, fosfluconazole ( 2 ), a water-soluble prodrug of Diflucan, and the subsequent development of a commercial route is presented. Particular items to note are (i) that this compound was discovered in the Chemical Research and Development Department, hence Chemical Research and Development can play a key role in prodrug discovery, (ii) the strategy behind the selection of phosphate ester promoiety, by phosphorylation of a sterically hindered tertiary alcohol, (iii) the development of the initial route to remove thermally hazardous reagents and to improve processing to allow scale-up, and (iv) the identification and development of the proposed commercial process.",10.1021/op010064+,2001-12-18,0.5960895329681081
Synlett,"An Expeditious Synthesis of 2,2’-Biindolyl","All articles of this category Treatment of 1,4-di(2-ethoxycarbonylaminophenyl)-butadiyne, obtained from 2-iodoaniline in four steps, with sodium ethoxide in refluxing ethanol furnishes 2,2’-biindolyl in one step in an excellent yield. 2,2’-biindolyl - cross-coupling reaction - homo-coupling reaction - indole synthesis - palladium catalyst",10.1055/s-1995-5110,1995-08-01,0.5960864720821593
Tetrahedron,"Stereoselective synthesis of steroid side chain and CD-rings. A route to (±)-de-ab-cholesta-8(14),22-dien-9-one",,10.1016/s0040-4039(00)88931-5,1985-01-01,0.5960863502788925
Journal of Organic Chemistry,"Microwave-Assisted Syntheses of <i>N</i>-Heterocycles Using Alkenone-, Alkynone- and Aryl-carbonyl <i>O</i>-Phenyl Oximes: Formal Synthesis of Neocryptolepine","This research aimed to provide a new and ""clean"" synthetic method that would enable both known and novel N-heterocycles to be prepared efficiently. O-Phenyl oximes were found to be excellent precursors for iminyl radicals with a variety of acceptor side chains. Dihyropyrroles were made in good yields from O-phenyl oximes containing pent-4-ene acceptors. The analogous process with a hex-5-enyl acceptor did not yield a dihydropyridine, probably because the 6-exo-trig ring closure of the iminyl radical was too slow to compete with H-atom abstraction. The iminyl radical from a precursor with a pent-4-yne type side chain underwent ring closure followed by rearrangement to afford a pyrrole derivative. Suitably substituted iminyl radicals ring closed readily onto aromatic acceptors, thus enabling several polycyclic systems to be accessed. Quinolines were made from 3-phenylpropanones via their O-phenyl oximes. Syntheses of phenanthridines starting from 2-formylbiphenyls were particularly efficient, and this approach enabled the natural product trisphaeridine to be made. Starting from 2-phenylnicotinaldehyde derivatives, ring closures of the derived iminyl radicals onto the phenyl rings yielded benzo[h][1,6]naphthyridines. Similarly, ring closure onto a phenyl ring from a benzothiophene-based iminyl yielded a benzo[b]thieno[2,3-c]quinoline. By way of contrast, iminyl radical ring closure onto pyridine rings was not observed. However, iminyl radicals did cyclize onto indoles, enabling indolopyridines to be prepared. The latter route was exploited in a short formal synthesis of neocryptolepine starting from 2-((1H-indol-3-yl)methyl)cyclohexanone.",10.1021/jo800847h,2008-06-13,0.596084590731641
Journal of Organic Chemistry,Synthesis of a Sulfonium Ion Analogue of the Glycosidase Inhibitor Swainsonine,"The synthesis of a bicyclic sulfonium ion analogue of a naturally occurring indolizidine alkaloid, swainsonine, in which the bridgehead nitrogen atom is replaced by a sulfonium ion, has been achieved by a multistep synthesis starting from (2S,3S,4R)-2,3-dibenzyloxy-4-formaldehyde-thiolane. The synthetic strategy relies on the intramolecular displacement of a leaving group on a pendant acyclic chain by a cyclic thioether. This bicyclic sulfonium salt provides a candidate with which to further probe the hypothesis that a sulfonium salt carrying a permanent positive charge would be an effective glycosidase inhibitor.",10.1021/jo052111s,2005-12-27,0.5960759835355856
Journal of Organic Chemistry,"Synthesis of Enantiopure Cis- and Trans <i>-</i> 2,3-Disubstituted Piperidines","The synthesis of enantiopure cis- and trans-2,3-disubstituted piperidines 4 is described. The key step of the synthesis involves the stereoselective reduction of chiral nonracemic lactams 2 by using BH3.Me2S. A rationalization of the stereoselectivity is presented.",10.1021/jo025955+,2002-09-26,0.5960718959056893
Synlett,Efficient Synthesis of 1-Thiomansonones with Anti-MRSA Activity,"In this study, we developed an efficient and general synthetic strategy for thiaphenalene, a sulfur-containing polyaromatic hetero­cycle, and applied for the synthesis of 1-thio derivatives of mansonone I and F, natural 1-oxaphenalenic orthoquinones. The pivotal steps for the construction of thiophenalene skeleton include formation of arylsulfide by Newman–Kwart rearrangement of thiocarbamate or palladium-­catalyzed cross-coupling, and pericyclic ring closure. Three bioisosterically modified orthoquinones were synthesized and were evaluated for anti-MRSA activity.",10.1055/s-0036-1591894,2018-01-29,0.596057679405218
Tetrahedron,Protein kinase C modulators. Indolactams. 1. Efficient and flexible routes for the preparation of (-)-indolactam V for use in the synthesis of analogs,,10.1016/s0040-4039(00)78433-4,1994-11-01,0.5960563455134485
Organic Letters,Synthesis of Angiolam A,"The first total synthesis of angiolam A has been accomplished in 18 steps. Key steps include vinylogous Mukaiyama aldol reactions of aldehyde-derived dienol ethers, conjugate reduction of the resulting double bond followed by diastereoselective protonation and the Witzeman protocol for macrolactamization. Comparison of the optical rotation of the synthesized material with the isolation data established that the absolute configuration of angiolam A is opposite from the proposed structure.",10.1021/ol403423r,2013-12-16,0.5960547102517652
Organic Letters,"Synthesis of the Parent and Substituted Tetracyclic ABCD Ring Cores of Camptothecins via 1-(3-Aryl-2-propynyl)- 1,6-dihydro-6-oxo-2-pyridinecarbonitriles","A new synthetic pathway to the parent and substituted ABCD ring cores of the camptothecin family of alkaloids was developed. The N-alkylation of 1,6-dihydro-6-oxo-2-pyridinecarbonitrile (2) with 3-bromo-1-phenylpropyne provided 3a using Curran's protocol. Treatment of 3a with a catalytic amount of DBU (5 mol %) at 110 degrees C for 12 h produced indolizino[1,2-b]quinolin-9(11H)-one (6a), the parent ABCD ring core of camptothecin, in essentially quantitative yield.",10.1021/ol0620242,2006-09-01,0.5960536849217137
European Journal of Organic Chemistry,Highly Efficient Total Synthesis of the <i>Clostridium</i>‐Derived anti‐MRSA Antibiotic Closthioamide,"Abstract The antibiotic closthioamide from Clostridium cellulolyticum , the first example of a secondary metabolite from strictly anaerobic bacteria, was synthesized by a versatile and highly efficient synthetic route. This starts from simple building blocks and involves convergent peptide coupling and polythionation.",10.1002/ejoc.201001695,2011-02-03,0.5960462580692942
Tetrahedron,π-Allyl palladium ring closure strategy for the synthesis of a 1β-methylcarbapenem intermediate,,10.1016/0040-4039(95)00448-l,1995-04-01,0.5960462369871328
Synlett,Efficient One-Step Synthesis of Optically Pure (Adenin-8-yl)phenylalanine Nucleosides,"An efficient single-step synthesis of optically pure (adenin-8-yl)phenylalanine nucleosides, a new type of purine amino acid conjugate, by palladium-catalyzed cross-coupling reactions of unprotected 8-bromoadenosines with 4-(borono)phenylalanine was developed.",10.1055/s-2005-921896,2005-10-27,0.5960425819739432
European Journal of Organic Chemistry,"Synthesis of Racemic 2‐(Aminomethyl)cyclopropane‐1,1‐dicarboxylic Acid as a New Constrained γ‐Amino Dicarboxylic Acid Bypassing Alkyl 3‐Aza‐2‐oxobicyclo[3.1.0]hexane‐1‐carboxylates","The first synthesis of racemic 2‐(aminomethyl)cyclopropane‐1,1‐dicarboxylic acid was developed involving sequential iodocarbocyclization, azidation, saponification and reduction of dimethyl 2‐allylmalonate. The developed synthetic pathway avoids reactions such as ring opening of the cyclopropane ring toward acyclic δ‐amino carboxylic acid derivatives or lactamisation toward bicyclic methyl 3‐aza‐2‐oxobicyclo[3.1.0]hexane‐1‐carboxylates which occur in alternative synthetic strategies.",10.1002/ejoc.201900542,2019-05-28,0.5960361423990026
Organic Letters,Tandem Single-Step Construction of Chiral Hexahydrophenanthrenes:  A Concise Route to (+)-Ferruginol,An efficient enantio- and diastereocontrolled construction of hydrophenanthrenes having either a quaternary or a tertiary benzylic stereogenic center has been developed by employing a tandem retro-aldol and intramolecular Friedel-Crafts alkylation sequence. Its application to a diastereocontrolled synthesis of an abietane diterpenoid (+)-ferruginol has also been demonstrated.,10.1021/ol015929i,2001-05-01,0.5960349279949797
Journal of Organic Chemistry,Enantioselective Approach to Polyhydroxylated Compounds Using Chiral Sulfoxides:  Synthesis of Enantiomerically Pure <i>myo</i>-Inositol and Pyrrolidine Derivatives,"A short enantioselective synthesis of the biologically important myo -inositol derivative I and the pyrrolidine derivative II is described. The molecule 3, a diketo disulfoxide readily made from tartaric acid, is the key intermediate. The sulfinyl group controlled completely the very high stereoselection observed.",10.1021/jo9811569,1998-11-01,0.5960332588158483
European Journal of Organic Chemistry,Enantioselective Synthesis of Spiroimines by Asymmetric Decarboxylative Alkylation/Isomerization/[3+2]‐Cycloaddition Reaction of Azidoalkenes,"Abstract The synthesis of chiral spiroimines, one of the pharmacophores of the marine neurotoxin gymnodimine A is described. The approach relies on a three‐step sequence that includes a palladium‐catalyzed asymmetric decarboxylative alkylation, an isomerization and a [3+2]‐cycloaddition reaction of an azidoalkene to build the imine.",10.1002/ejoc.201403161,2014-10-24,0.5960330207174898
Organic Process Research & Development,Early Kilogram Scale Delivery of MK-7845 as a Potential COVID-19 Therapy: Rapid Process Development of Key Intermediates,"MK-7845 was designed as a 3C-like protease inhibitor for the treatment of COVID-19. To enable a rapid kilo-scale delivery of MK-7845 to accelerate its First-in-Human studies, we developed a fit-for-purpose process to produce two key building blocks in less than two months. The key discoveries were a highly diastereoselective Ellman addition route for β-aminoamide 6 and crystallization isolation methods to produce 6 and acid 9 with good quality control.",10.1021/acs.oprd.4c00003,2024-05-16,0.5960276887701855
Organic Letters,Coumarins from Free <i>ortho</i>-Hydroxy Cinnamates by Heck-Matsuda Arylations: A Scalable Total Synthesis of (<i>R</i>)-Tolterodine,"Free ortho-hydroxy cinnamate ester derivatives are evaluated in the synthesis of structurally diverse 4-aryl-coumarins via a tandem Heck-Matsuda cyclization reaction. Free phenolic groups were considered incompatible with such a reaction, which usually provide the corresponding diazo dyes. A concise and scalable route employing a ligand-free, Pd-catalyzed Heck-Matsuda arylation under aerobic conditions for the preparation of (R)-Tolterodine in high overall yield and ee is also presented.",10.1021/ol302923f,2012-11-28,0.5960247524272674
Journal of Organic Chemistry,Base-Catalyzed Isomerization of 2-Isoxazolines Enables a Two-Step Enantioselective Synthesis of β-Hydroxynitriles from Enals,"The asymmetric synthesis of β-hydroxynitriles remains a challenge in organic synthesis. Herein we report a convenient synthesis of β-hydroxynitriles from enantiomerically enriched 3-unsubstituted 2-isoxazolines via a base-catalyzed ring-opening reaction that takes place without loss of enantiopurity. In combination with organocatalytic enantioselective synthesis of 3-unsubstituted 2-isoxazolines, the ring-opening enables a short 2-step synthesis of β-hydroxynitriles from α,β-unsaturated aldehydes in high enantiomeric purity.",10.1021/jo1013788,2010-09-08,0.5960246616507415
Journal of the American Chemical Society,Total Synthesis of (−)-Himalensine A,"The first enantioselective synthesis of (-)-himalensine A has been achieved in 22 steps. The synthesis was enabled by a novel catalytic, enantioselective prototropic shift/furan Diels-Alder (IMDAF) cascade to construct the ACD tricyclic core. A reductive radical cyclization cascade was utilized to build the B ring, and end-game manipulations featuring a molecular oxygen mediated γ-CH oxidation, a Stetter cyclization to access the pendant cyclopentenone, and a highly chemoselective lactam reduction delivered the natural product target.",10.1021/jacs.7b10956,2017-11-09,0.5960208879693853
Tetrahedron,An efficient synthesis of 2-ethoxycarbonylcarbapen-1-em-3-carboxylic acid,,10.1016/s0040-4039(01)92896-5,1981-01-01,0.596019888433831
Angewandte Chemie International Edition,Methylene C(sp<sup>3</sup>)−H Arylation Enables the Stereoselective Synthesis and Structure Revision of Indidene Natural Products,"Abstract The divergent synthesis of two indane polyketides of the indidene family, namely (±)‐indidene A (11 steps, 1.7 %) and (+)‐indidene C (13 steps, 1.3 %), is reported. The synthesis of the trans ‐configured common indane intermediate was enabled by palladium(0)‐catalyzed methylene C(sp 3 )−H arylation, which was performed in both racemic and enantioselective (e.r. 99 : 1) modes. Further elaboration of this common intermediate by nickel‐catalyzed dehydrogenative coupling allowed the rapid installation of the aroyl moiety of (±)‐indidene A. In parallel, the biphenyl system of (±)‐ and (+)‐indidene C was constructed by Suzuki–Miyaura coupling. These investigations led us to revise the structures of indidenes B and C.",10.1002/anie.202316103,2023-11-24,0.596012743363621
Tetrahedron,"An unexpected Pummerer rearrangement in the synthetic route to ethyl (2′-hydroxy-4′,5′-methylenedioxyphenyl)acetate: An alternative approach to 2,3-dimethylthio benzofurans",,10.1016/j.tetlet.2019.151282,2019-10-14,0.59601267437426
Synlett,A Concise Preparation of an Appropriately Functionalized B-seco Taxane Derivative,"All articles of this category A successful route to a B-seco taxoid framework of type 2 , which may be further manipulated in the expedient synthesis of taxoid ABC-core using standard synthetic procedures is described. B-seco taxanes - organostannanes - kinetic discrimination",10.1055/s-1998-1833,1998-09-01,0.5960106468204052
European Journal of Organic Chemistry,Formal Synthesis of Galantinic Acid by Oxo‐Diels–Alder Methodology,"Abstract This communication presents a simple and efficient enantioselective route to galantinic acid. The strategy is based on a highly enantioselective hetero‐Diels–Alder (HDA) reaction of 3‐(4‐methoxybenzyloxy)propanal with Danishefsky's diene followed by selective introduction of further stereogenic centers thanks to the rigidity of the dihydropyran ring. The key HDA reaction is catalyzed by a new salen Cr III complex bearing a 1,1‐diphenylethyl substituent at the 3‐position of the salicyliden moiety.",10.1002/ejoc.201001296,2011-01-27,0.5960087282147121
Angewandte Chemie International Edition,Enantioselective Synthesis of Cyclic Ethers through a Vanadium‐Catalyzed Resolution/Oxidative Cyclization,"Two steps, one catalyst: A vanadium(V)–oxo complex with a tridentate Schiff base as an additional ligand catalyzes the title reaction which transforms racemic bishomoallylic α-hydroxyesters into trans-tetrahydropyrans (THPs) and cis-tetrahydrofurans (THFs). This synthetic method provides an efficient asymmetric synthesis of cyclic ethers as demonstrated by the first enantioselective synthesis of (−)-pantofuranoid E. TBHP=tert-butylhydroperoxide.",10.1002/anie.200503852,2006-02-27,0.5960085887431924
Organic Letters,"Regioselective Synthesis of Pyrazolo[1,5-<i>a</i>]pyridine via TEMPO-Mediated [3 + 2] Annulation–Aromatization of<i>N</i>-Aminopyridines and α,β-Unsaturated Compounds","A TEMPO-mediated [3 + 2] annulation–aromatization protocol for the preparation of pyrazolo[1,5- a ]pyridines from N -aminopyridines and α,β-unsaturated compounds was developed. The procedure offered multisubstituted pyrazolo[1,5- a ]pyridines in good to excellent yield with high and predictable regioselectivity. The modification of marketed drugs including Loratadine, Abiraterone, and Metochalcone, and a one-pot three-step gram scale synthesis of key intermediate for the preparation of Selpercatinib were demonstrated. Mechanism studies show that TEMPO serves both as a Lewis acid and as an oxidant.",10.1021/acs.orglett.2c00035,2022-02-15,0.5960079690264042
Journal of Organic Chemistry,Early Amidation Approach to 3-[(4-Amido)pyrrol-2-yl]-2-indolinones,"A new synthesis of 3-[(4-amido)pyrrol-2-yl]-2-indolinones has been developed, where the amide side chain was installed prior to pyrrole formation. This strategy precludes the need to use any coupling reagents to install the amide side chain. This process includes a zinc-free alternative to the Knorr pyrrole synthesis.",10.1021/jo034304q,2003-07-11,0.5960065321259225
Organic Letters,A New RNA Synthetic Method with a 2‘- <i>O</i> -(2-Cyanoethoxymethyl) Protecting Group,A novel method for the synthesis of RNA oligomers with 2-cyanoethoxymethyl (CEM) as the 2'-hydroxyl protecting group has been developed. The new method allows the synthesis of oligoribonucleotides with an efficiency and final purity comparable to that obtained in DNA synthesis. [structure: see text],10.1021/ol051151f,2005-07-07,0.5960064185162486
Journal of Organic Chemistry,"Combined Directed Remote Metalation−Transition Metal Catalyzed Cross Coupling Strategies: The Total Synthesis of the Aglycones of the Gilvocarcins V, M, and E and Arnottin I","A key directed remote metalation (DreM)-carbamoyl migration strategy was applied in an efficient synthesis of the naturally occurring 6H-naphtho[1,2-b]benzopyran-6-one defucogilvocarcin V (1a, Scheme 11). The required biarylcarbamate 33d was best prepared by a high yielding Suzuki coupling reaction of 31a with the differentially protected trioxygenated naphthalene coupling partner 32d which was synthesized using a selective acylation of a juglone derivative. In the late stages of the synthesis, the triflate 39 served as the common intermediate to install the required C-8 vinyl group of 1a (Stille coupling) as well as the required substituents for the preparation of defucogilvocarcins M (1b) and E (1c). A variety of protecting group strategies were investigated and provided insight into which groups are preferred for the DreM-carbamoyl migration process. The strategic lessons learned from this total synthesis were applied in the successful total synthesis of the structurally similar natural product arnottin I (2).",10.1021/jo9001454,2009-05-14,0.5959956710027492
Organic Letters,Pd(II)-Catalyzed C4-Selective Alkynylation of Indoles by a Transient Directing Group,"With alanine as a transient directing group, Pd-catalyzed regioselective alkynylation at the indole C4-position was successfully established in a good yield. The total synthesis of the PAF antagonist demonstrated the synthetic utility of this protocol. The regioselectivity was explicitly proven by the prepared C4-selective palladacycle intermediate in the catalytic process and the DFT calculation of the energy barriers of C4- and C2-site-selective C-H activation of indole.",10.1021/acs.orglett.4c01970,2024-08-06,0.5959925835276346
Tetrahedron,"Synthesis and resolution of 2-methyl-Quinazolinap, a new atropisomeric phosphinamine ligand for asymmetric catalysis",,10.1016/s0040-4039(00)00183-0,2000-04-01,0.5959881411093169
Journal of Organic Chemistry,A Unified Stereodivergent Strategy for Prostaglandin and Isoprostanoid Synthesis,"Acetoxyfulvene surrended to asymmetric Diels-Alder cycloaddition, paving the way to the development of a unified strategy for the stereodivergent synthesis of both prostaglandins and isoprostanoids. In fact, the cycloadduct was subsequently converted to a common intermediate, which through two different stereoselective pathways afforded the two lactones 1 and 2, which are key building blocks in the synthesis of prostaglandins and isoprostanoids, respectively.",10.1021/jo500093k,2014-02-19,0.5959860530365824
Journal of the American Chemical Society,Catalytic Enantioselective Addition of Dialkylzinc to <i>N</i>-Diphenylphosphinoylimines. A Practical Synthesis of α-Chiral Amines,"The enantioselective addition of dialkylzinc reagents to N-diphenylphosphinoylimines derived from aryl-, furyl-, and cyclopropylaldehydes is efficiently catalyzed by a copper(II) triflate/(R,R)-MeDUPHOS complex. The yields are high (51-98%), and the enantiomeric excesses vary from 85 to 96%. This route provides a practical route to alpha-chiral amines.",10.1021/ja027673x,2003-01-21,0.5959859473507458
Tetrahedron,An expedient atom-efficient synthesis of the cannabinoid CB1 receptor inverse agonist ibipinabant,,10.1016/j.tetlet.2011.01.068,2011-01-22,0.5959809312213575
Tetrahedron,Synthesis of olivanic acid analogues: a facile route to 3-(2-pyrimidinylthio-) substituted derivatives,,10.1016/s0040-4039(00)71137-3,1980-01-01,0.5959788895769228
Tetrahedron,"An efficient and diastereoselective [2+2] cycloaddition: convenient and enantioselective route to trans-2′,3′-dihydroxymethylcyclobutane nucleoside analogs",,10.1016/0040-4039(91)85023-x,1991-11-01,0.595976702407965
Organic Letters,Total Synthesis of (±)-Nardoaristolone B and Its Analogues,"The first total synthesis of nardoaristolone B, a nor-sesquiterpenoid with an unusual fused ring system and having protective effects on the injury of neonatal rat cardiomyocytes, has been accomplished. Stereoselective synthesis of its novel analogues inlcuding exo-cyclopropyl ring fusion is also part of this disclosure. In addition, an alternate and more efficient one-step method to make a 3/5/6 tricyclic ring system using the Robinson annulation method has been developed toward the generation of a library of compounds around this skeleton.",10.1021/ol501949r,2014-07-31,0.595974525824491
Synthesis,"Connecting C19 Norditerpenoids to C20 Diterpenes: Total Syntheses of 6-Hydroxy-5,6-dehydrosugiol, 6-Hydroxysugiol, and Taiwaniaquinone H, and Formal Synthesis of Dichroanone","Oxidation of the B-ring of abietane derivatives by Sharpless dihydroxylation gave the natural products 6-hydroxy-5,6-dehydrosugiol and 6-hydroxysugiol. Moreover, further oxidation gave a hydroxy dione derivative that provides a synthetic entry into the C-19 taiwaniaquinoid family of natural products. This route is based on biosynthetic considerations and involves a benzilic acid rearrangement followed by decarboxylation. On the basis of this approach, a total synthesis of (-)-taiwaniaquinone H and a formal synthesis of (-)-dichroanone have been achieved.",10.1055/s-0029-1218806,2010-05-28,0.5959633219913769
Organic Letters,"Au-Catalyzed Asymmetric Polyene Cyclization and Its Application in the Total Synthesis of (+)-2-Ketoferruginol, (+)-Fleuryinol B, (+)-Salviol, and (−)-Erythroxylisin A","A catalytic asymmetric 1,3-acyloxy shift/polyene cyclization cascade has been achieved with good enantioselectivities under the catalysis of the chiral Au(I) reagent. The synthetic utility of this method has been showcased by the catalytic asymmetric total syntheses of (+)-2-ketoferruginol, (+)-fleuryinol B, and (+)-salviol. Notably, the first enantioselective total synthesis of (-)-erythroxylisin A has also been realized in 15 steps.",10.1021/acs.orglett.3c02417,2023-10-09,0.595961989475653
Tetrahedron,A stereocontrolled synthesis of the key intermediate of (+)-thienamycin from ()-(−)-3-hydroxybutyric acid esters,,10.1016/s0040-4039(00)95651-x,1987-01-01,0.5959611320063041
European Journal of Organic Chemistry,"A Protection‐Free Synthetic Access to (±)‐1‐Deoxy‐6‐<i>epi</i>‐castanospermine and (±)‐1‐Deoxy‐6,8a‐di‐<i>epi</i>‐castanospermine","Abstract A new synthesis of (±)‐1‐deoxy‐6‐ epi ‐castanospermine and (±)‐1‐deoxy‐6,8a‐di‐ epi ‐castanospermine has been developed, starting from the hetero‐Diels–Alder adduct of ethyl 2‐nitrosoacrylate and ethyl vinyl ether. Appropriate terminal dienes were prepared by standard manipulations, which, upon RCM followed by dihydroxylation and catalytic Raney Ni hydrogenation, led to the title compounds, which are of significant biological interest. The whole synthesis was completed in eight steps, and no protecting groups were needed in any step.",10.1002/ejoc.201201334,2012-12-19,0.5959549524394907
Synlett,An Efficient Stereocontrolled Synthesis of (R)-2-Carboxy-4-(3-phosphonopropyl)piperazine [(R)-CPP],"All articles of this category The amino acid ( R )-CPP ( 1 ), a selective antagonist of the NMDA receptor, is prepared directly in enantiopure form starting from L-serine and sarcosine. Unnatural α-amino acids - chiral piperazines - CPP - NMDA antagonists",10.1055/s-1996-5341,1996-02-01,0.5959451433424799
Tetrahedron,An efficient (one-pot) synthesis of a new class of cyclophanes,,10.1016/s0040-4039(98)00119-1,1998-04-01,0.5959420266665231
Tetrahedron,"A novel one-pot synthesis of 7-methoxy-2-arylthieno[3,2-b]pyridine-3-ols in domino fashion",,10.1016/j.tetlet.2013.07.024,2013-07-11,0.5959413651656672
Journal of Organic Chemistry,Total Synthesis of Borrelidin,"The total synthesis of borrelidin has been achieved. The best feature of our synthetic route is macrocyclization at C11-C12 for the construction of an 18-membered ring after esterification between two segments. A detailed examination of the macrocyclization led us to the samarium(II) iodide-mediated intramolecular Reformatsky-type reaction as the most efficient synthetic approach. The two key segments were synthesized through regioselective methylation, directed hydrogenation, stereoselective Reformatsky-type reaction, and MgBr2.Et2O-mediated chelation-controlled allylation.",10.1021/jo062089i,2007-03-14,0.5959359306796629
Organic Letters,Conversion of Phorbol into Des-D-Ring Tricycle and Crotonianoid B via Peroxidation Reaction,"Phorbol ( 1 ) has a tetracyclic ABCD-ring and is readily isolable from a natural source. We previously synthesized 1 and 16 structurally related natural products using common ABC-ring intermediate 2 . Here we report a new synthetic route to 2 using 1 as a starting material. Key features of the synthesis are chemoselective removal of the D-ring via cyclopropane opening, peroxidation, and retro-aldol reactions. The high utility of the peroxidation was further demonstrated in the first synthesis of crotonianoid B ( 9 ).",10.1021/acs.orglett.4c01363,2024-05-13,0.5959354167230185
Tetrahedron,Chiral acetylenic sulfoxide in alkaloid synthesis. Total synthesis of (R)-(+)-carnegine.,,10.1016/0040-4039(91)80426-7,1991-11-01,0.5959309182966419
Organic Letters,"Formal Synthesis of Antiplatelet Drug, Beraprost",The first stereocontrolled and enantiospecific formal synthesis of antiplatelet drug beraprost has been achieved from readily available 1-tetralone.,10.1021/ol203060v,2011-12-14,0.5959147773358893
Chemical Science,Enantioselective construction of the tricyclic core of curcusones A–D <i>via</i> a cross-electrophile coupling approach,"carbocyclic core embedded in each member of the curcusone family. Essential to this route is the use of a cross-electrophile coupling strategy, which has not previously been harnessed in the context of natural product synthesis.",10.1039/c9sc04127c,2019-01-01,0.5959136280935189
Organic Letters,An Organocatalytic Approach to the Construction of Chiral Oxazolidinone Rings and Application in the Synthesis of Antibiotic Linezolid and Its Analogues,"An efficient, catalytic asymmetric approach to antibacterial agent linezolid has been developed. The route features organocatalytic, highly enantioselective aldol and Beckman rearrangement reactions. The strategy has also been successfully applied for the preparation of new alpha-substituted analogues with high enantio- and diastereoselectivity.",10.1021/ol802333n,2008-11-12,0.5959021708449563
European Journal of Organic Chemistry,Total Synthesis of Carbazomycin G,"Abstract A concise total synthesis of carbazomycin G has been completed in five steps. Cerium(IV) ammonium nitrate (CAN)–SiO 2 ‐mediated oxidation of 2‐methyl‐2,3,4,9‐tetrahydro‐1 H ‐ carbazol‐1‐one afforded a carbazole‐1,4‐quinone derivative, 2‐methyl‐1 H ‐carbazole‐1,4(9 H )‐dione, the synthetic precusor, which on, which, on Thiele acetylation under newly developed HBF 4 catalysis conditions, yielded 4‐hydroxy‐2‐methyl‐9 H ‐carbazole‐1,3‐diyl diacetate. Finally, CAN‐SiO 2 ‐mediated oxidative hydrolysis of the acetylation product and O ‐methylation using a stoichiometric amount of diazomethane and subsequent regioselective nucleophilic addition of methyllithium led to carbazomycin G.",10.1002/ejoc.201300467,2013-07-18,0.5958960772046276
Tetrahedron,"Synthesis of 3-[2-(1,3-butadienyl)]-1H-indoles en route to murrapanine analogue",,10.1016/j.tetlet.2011.10.003,2011-10-15,0.5958911015648476
Journal of Organic Chemistry,Sulfonyl-Stabilized Oxiranyllithium-Based Approach to Polycyclic Ethers. Convergent Synthesis of the ABCDEF-Ring System of Yessotoxin and Adriatoxin,"Convergent synthesis of the ABCDEF-ring system of yessotoxin and adriatoxin, marine polycyclic ether toxins causative of diarrheic shellfish poisoning, has been accomplished. The A-ring fragment was constructed by coupling of an appropriately functionalized sulfonyl-stabilized oxiranyl anion and a triflate prepared from an erythritol derivative. An iterative protocol of the oxiranyl anion strategy was also applied for the construction of the DEF-ring fragment. The triflate derivatives of the A-ring and the DEF-ring fragments were connected with lithium acetylide. The resulting acetylene derivative was further transformed into the hexacyclic ABCDEF fragment via oxidation of the acetylene unit to 1,2-diketone, double methyl acetal formation, and reductive etherification.",10.1021/jo035145d,2003-10-22,0.5958907623143492
Journal of the American Chemical Society,"Enantioselective Total Syntheses of Akuammiline Alkaloids (+)-Strictamine, (−)-2(<i>S</i>)-Cathafoline, and (−)-Aspidophylline A","The akuammiline alkaloids are a family of natural products that have been widely studied for decades. Although notable synthetic achievements have been made recently, akuammilines that possess a methanoquinolizidine core have evaded synthetic efforts. We report an asymmetric approach to these alkaloids, which has culminated in the first total syntheses of (-)-2(S)-cathafoline and the long-standing target (+)-strictamine. Moreover, the first enantioselective total synthesis of aspidophylline A is described.",10.1021/jacs.5b12880,2016-01-19,0.5958852211409443
Organic Letters,First Total Synthesis and Stereochemical Definition of Isodomoic Acid G,"[structure: see text] The first total synthesis and stereochemical definition of isodomoic acid G has been achieved. The key nickel-catalyzed coupling of an alkynyl enone with an alkenylzirconium allows formation of the pyrrolidine ring and most of the stereochemical features in a single step. This report provides the first total synthesis application of this new reaction and illustrates its utility in the stereoselective preparation of highly substituted 1,3-dienes.",10.1021/ol0355783,2003-09-06,0.5958818544337098
Synthesis,Total Synthesis of an Antifouling Marine Furanosesquiterpene,An antifouling sesquiterpene isolated from Sinularia sp. was synthesized from citronellyl acetate in eight steps and 9% overall yield. The furan moiety was constructed using a multifunctional sulfone reagent.,10.1055/s-0036-1588711,2017-02-10,0.5958817232467271
Tetrahedron,Synthesis of a novel C-6 nigrogen-substituted carbapenem from 6-aminopenicillanic acid,,10.1016/s0040-4039(00)85833-5,1982-01-01,0.595873384905721
Organic Letters,Total Synthesis of Anti-tuberculosis Natural Products Ilamycins E<sub>1</sub> and F,"The first total synthesis of the potent anti-tuberculosis cyclopeptide natural products ilamycins E 1 and F was achieved. This highly convergent strategy consists of the synthesis of the two units 10 and 11 and linking them together to form the macrocyclic lactam 31 . The upper unit 10 was prepared from tryptophan in five steps, and the lower unit 11 was prepared from glutamic acid in thirteen steps. Conversion of ilamycin F, the most abundant of the cyclopeptides, into the more active congener, ilamycin E 1, was also accomplished. This would provide sufficient material of ilamycin E 1 for more extensive biological studies.",10.1021/acs.orglett.8b02643,2018-09-25,0.5958545206234703
Journal of the American Chemical Society,Bioinspired Synthesis of Spirochensilide A from Lanosterol,"A bioinspired synthesis of spirochensilide A from commercially available lanosterol is reported. The synthesis features a directed C-H oxidation, a Wagner-Meerwein-type double methyl migration, a Meinwald rearrangement, and a double-bond isomerization/spiroketal formation cascade. The proposed biosynthetic speculation was modified by this synthetic sequence, which also served as a platform for the synthesis of other lanostanes with migrating methyl groups.",10.1021/jacs.2c07198,2022-09-02,0.5958513785372914
Journal of Organic Chemistry,"Development of Versatile <i>cis</i>- and <i>trans</i>-Dicarbon-Substituted Chiral Cyclopropane Units:  Synthesis of (1<i>S</i>,2<i>R</i>)- and (1<i>R</i>,2<i>R</i>)-2-Aminomethyl-1-(1<i>H</i>-imidazol-4-yl)cyclopropanes and Their Enantiomers as Conformationally Restricted Analogues of Histamine","The cyclopropane ring can be used effectively in restricting the conformation of biologically active compounds to improve activity and also to investigate bioactive conformations. We designed (1S,2R)- and (1R,2R)-2-aminomethyl-1-(1H-imidazol-4-yl)cyclopropanes (1 and 2, respectively) and their enantiomers (ent-1 and ent-2) as conformationally restricted analogues of histamine. The four types of chiral cyclopropanes bearing two differentially functionalized carbon substituents in a cis or trans relationship on a cyclopropane ring, (1S,2R)-2-(tert-butyldiphenylsilyloxy)methyl-1-formylcyclopropane (7) and (1R,2R)-2-(tert-butyldiphenylsilyloxy)methyl-1-formylcyclopropane (8) and their enantiomers (ent-7 and ent-8), were developed as the key intermediates for synthesizing 1, 2, ent-1, and ent-2. The reaction between (R)-epichlorohydrin [(R)-12] and phenylsulfonylacetonitrile (13a) in the presence of NaOEt in EtOH followed by treatment with acid gave the chiral cyclopropane lactone 11a with 98% ee in 82% yield. Compound 11a was converted into both the cis- and trans-chiral cyclopropane units 7 and 8, respectively, via reductive desulfonylation with Mg/MeOH as the key step. The corresponding enantiomers, the cis-substituted ent-7 and the trans-substituted ent-8, were also prepared starting from (S)-epichlorohydrin [(S)-12]. The four conformationally restricted target histamine analogues 1, 2, ent-1, and ent-2 were successfully synthesized from 7, 8, ent-7, and ent-8, respectively. The chiral cyclopropane units 7, 8, ent-7, and ent-8 should be useful as versatile intermediates for synthesizing various compounds having an asymmetric cyclopropane structure.",10.1021/jo010852x,2002-02-01,0.5958417966399787
Tetrahedron,Synthesis of thiophenes from acetylenes and -amine disulfides,,10.1016/s0040-4039(01)83254-8,1977-01-01,0.5958409557181846
Tetrahedron,"A conformational study of R-alaproclate, a new selecetive inhibitor of neuronal 5-hydroxytryptamine uptake",,10.1016/0040-4039(78)80042-2,1978-01-01,0.5958362913691448
Tetrahedron,"The structure of allosamidin, a novel insect chitinase inhibitor, produced by Streptomyces Sp.",,10.1016/s0040-4039(00)84560-8,1986-01-01,0.5958299722446996
Tetrahedron,"Structure of a novel phospholipase C inhibitor, vinaxanthone (Ro 09-1450), produced by penicillium vinaceum",,10.1016/s0040-4039(00)92295-0,1991-01-01,0.5958299722446996
Journal of the American Chemical Society,Total Synthesis of Epoxyeujindole A,"The total synthesis of epoxyeujindole A, a structurally unusual indole diterpenoid isolated from Eupenicillium javanicum, has been accomplished for the first time. The synthesis features a late-stage cationic cyclization strategy, which took advantage of an electron-rich olefinic substrate. The CDE ring system was assembled via an enantioselective conjugate addition/alkylation, a Luche cyclization, and a Nozaki-Hiyama-Kishi reaction. The heavily substituted A ring was constructed through a Suzuki-Miyaura coupling and a cationic cyclization, and the bridged fused B ring was formed through a Prins reaction.",10.1021/jacs.5b09198,2015-09-23,0.5958295261865412
Tetrahedron,A new general synthesis of α-oxodimethylketals and α-diketones: An improved bissulfenylation of α-oxomethylenes,,10.1016/s0040-4039(01)85798-1,1978-01-01,0.5958237861191831
Tetrahedron,An efficient method for the alkylation of chiral triflates with alkynyllithium reagents. A highly concise total synthesis of (+)-panaxacol,,10.1016/s0040-4039(00)97688-3,1990-01-01,0.5958237703408044
Journal of Organic Chemistry,"Synthesis of the Reported Pyranonaphthoquinone Structure of the Indoleamine-2,3-dioxygenase Inhibitor Annulin B by Regioselective Diels–Alder Reaction","Annulin B, isolated from the marine hydroid isolated from Garveia annulata, is a potent inhibitor of the tryptophan catabolizing enzyme indoleamine-2,3-dioxygenase (IDO). A synthesis of the reported pyranonaphthoquinone structure is described, in which the key step is a regioselective Diels-Alder reaction between a pyranobenzoquinone dienophile and a silyl ketene acetal diene.",10.1021/acs.joc.6b01622,2016-08-11,0.5958217047278538
Journal of Organic Chemistry,Perylenequinone Natural Products: Total Synthesis of Hypocrellin A,"An efficient and stereoselective total synthesis of the perylenequinone natural product hypocrellin A (1) is described. The key features include a potentially biomimetic 1,8-diketone aldol cyclization to set the centrochiral C7,C7'-stereochemistry, bis(trifluoroacetoxy)iodobenzene mediated oxygenation, a palladium-catalyzed decarboxylation, and an enantioselective catalytic oxidative 2-naphthol coupling to establish the biaryl axial chirality. The helical stereochemistry is formed from an axial chiral intermediate and is then utilized in a dynamic stereochemical transfer to dictate the stereochemistry of the C7,C7'-seven membered ring formed during the aldol cyclization.",10.1021/jo901386d,2009-11-09,0.5958203861231914
Tetrahedron,Synthesis of macrocyclic terpenoids by intramolecular cyclization IV. Synthesis of 6z-hedycaryols,,10.1016/s0040-4039(01)94959-7,1978-01-01,0.5958149393051637
Tetrahedron,"An enantioselective synthesis of a 6,7-bentzomorphan through the cyclisation of the chromium tricarbonyl complex of an 1-(aminoethan-2′-yl)- 1,2-dihydronaphthalene",,10.1016/s0040-4039(00)94693-8,1990-01-01,0.595812792270788
Tetrahedron,"Synthesis of (2S,4S,6S)-2-amino-6-hydroxy-4-methyl-8 oxodecanoic acid and (4S,E)-4-methylhex-2-enoic acid constituents of leucinostatines",,10.1016/0040-4039(91)80606-7,1991-08-01,0.5958044633582578
Tetrahedron,"Synthesis and complexation properties of a synthetic receptor, Z-tetrabenzohexadehydro[16]annulene",,10.1016/s0040-4039(01)01399-5,2001-09-01,0.595802110687444
Synlett,"Progress towards the Total Synthesis of Scytonemin A: Asymmetric Synthesis of (2S,3R,4R)-4-hydroxy-3-methylproline","During the total synthesis of the novel cyclopeptide scytonemin A, the fragment containing two (2S,3R,4R)-4-hydroxy-3-methylproline units was successfully prepared. Two approaches leading to (2S,3R,4R)-4-hydroxy-3-methylproline have been explored. They involve the following key transformations: asymmetric crotylation, Sharpless epoxidation-subsequent epoxide opening, intramolecular amidomercuration-oxidation.",10.1055/s-0029-1219208,2010-01-19,0.5958013055246597
Journal of the American Chemical Society,11-Step and Scalable Total Synthesis of Hamigeran M Enabled by Five C–H Functionalizations,"We report the convergent total synthesis of (±)-hamigeran M, enabled by five C-H functionalization reactions and proceeding in 11 steps in 3.9% overall yield. The C-H functionalizations include a hydroxy-directed C-H borylation, one C-H metalation-1,2-addition, one C-H metalation-Negishi coupling, a late-stage oxazole-directed C-H borylation-oxidation, and one electrophilic bromination. Two of these five C-H functionalizations forged strategic C-C bonds in the seven-membered ring of hamigeran M. The oxazole-directed C-H borylation-oxidation was unprecedented and ensured a late-stage hydroxylation. Other key steps include a tandem Suzuki reaction-lactonization to join the cyclopentane building block with the aromatic moiety and a hydrogen-atom transfer reaction to reduce a challenging tetrasubstituted double bond.",10.1021/jacs.1c11060,2021-11-23,0.595800748578436
Synthesis,Tricyclic Pyrazoles: An Efficient Approach to Cannabinoid Analogues with a Tricyclic Framework Incorporating the Pyrrole and Pyrazole Moieties,"In this paper we report the synthesis of some new cannabinoid analogues that share with rimonabant, a potent and selective CB 1 antagonist, the 2,4-dichlorophenyl and piperidin-1-yl substituents on the pyrazole and amide nitrogens, respectively. The general synthesis involves the preparation of a cyclic ketone condensed with a pyrrole, followed by Claisen condensation with diethyl oxalate; from here, an aza-annulation reaction with a substituted hydrazine followed by an amidation step complete the synthesis.",10.1055/s-0032-1316703,2012-07-31,0.5957998066994892
Organic Letters,Total Synthesis of the Proposed Structure of Briarellin J,The total synthesis of the originally proposed structure of briarellin J is reported in 15 steps from a known compound and in 23 steps from readily available materials. Key reactions include an exo-selective intramolecular Diels-Alder and a substrate-controlled hydroboration. Discrepancies in the spectroscopic data of the synthetic and natural material led to a revision of the assigned structure.,10.1021/ol102169w,2010-10-11,0.5957931472530739
Tetrahedron,An improved process for the synthesis of DMTMM-based coupling reagents,,10.1016/j.tetlet.2008.12.047,2008-12-17,0.595789249518039
Synthesis,Ring-Closing Metathesis Protocol for a Diastereocontrolled Synthesis of (-)-Shikimic Acid,"All articles of this category A new entry to (-)-shikimic acid, the key intermediate in the shikimate pathway in plants and microorganisms, has been devised by employing a ring-closing metathesis reaction as the key step starting with a 6,8-dioxabicyclo[3.2.1]octenone chiral building block. shikimic acid - chiral building block - enantiocontrolled synthesis - diastereocontrolled synthesis - ring-closing metathesis",10.1055/s-2000-7100,2000-01-01,0.5957888272032765
Synlett,Efficient Synthesis of<i>N</i>-Benzyloxycarbonyl- and<i>N</i>-<i>tert</i>-Butoxycarbonyl-(<i>S</i>)-Isoserine and their Derivatives,A mild and efficient synthesis of N-protected (S)-iso­serine from (S)-malic acid monoester via an oxazolidin-2-one is described.,10.1055/s-2002-35597,2002-01-01,0.5957887251368881
Organic Process Research & Development,New Manufacturing Route to Picoxystrobin,A new and efficient manufacturing technology is disclosed in the present work for the preparation of picoxystrobin in which all of the intermediates can be used directly in the next step of the process without purification.,10.1021/acs.oprd.5b00371,2016-01-26,0.5957827895215142
Journal of the American Chemical Society,Formal Synthesis of (−)-Kendomycin Featuring a Prins-Cyclization To Construct the Macrocycle,"The kendomycin skeleton was prepared by a highly convergent strategy in which the benzofuran fragment and the acyclic iodide fragment were prepared by standard methods and joined using a Suzuki coupling. The distinctive reaction in our approach was an intramolecular Prins cyclization that assembles the macrocyclic ring in good yield. Modeling studies demonstrate that the acyclic chain is predisposed for macrocycle formation. Ultimately, the product was correlated with one of Lee's advanced intermediates for a formal total synthesis of kendomycin.",10.1021/ja805187p,2008-09-04,0.5957812297395015
Synthesis,"Synthesis of Single-Enantiomer 6-Hydroxy-7-phenyl-1,4-oxazepan-5-ones","An efficient two-step preparation of (6R,7R)-6-hydroxy-7-phenyl-1,4-oxazepan-5-ones (1) starting from aminoethanols and (2R,3S)-3-phenyloxirane-2-carboxylic ethyl ester or potassium salt has been described. The most efficient catalyst identified for the ring closure of the resulting intermediate epoxyamides was Sc(OTf)3. By choice of appropriate chiral starting substituted aminoethanol and 3-phenyloxirane-2-carboxylic derivatives, the procedure allows facile synthesis of other single enantiomer 6-hydroxy-7-phenyl-1,4-oxazepan-5-ones.",10.1055/s-2005-872122,2005-08-04,0.5957781400897675
European Journal of Organic Chemistry,Trends in the Synthesis and Functionalization of Guaianolides,"Abstract Guaianolides constitute a large and diverse group of biologically active sesquiterpenes. Guaianolide and seco ‐guaianolides can also be used as, for example, scaffolds for the development of new active molecules that are readily accessible by synthetic methods. Nevertheless, these lactones often have complex structures that make their synthesis difficult. The aim of this microreview is to provide an overview of the developments in guaianolide synthesis by the two major synthetic strategies: semi‐synthesis and total synthesis. Partial and total syntheses of guaianolides are described, with particular emphasis placed on the methods reported in the last decade. The methods discussed include rearrangements, cycloadditions, ring‐closing metathesis, the use of transition‐metal catalysts, photochemical reactions, and other recently developed techniques as key steps.",10.1002/ejoc.201403244,2015-01-15,0.5957767077424762
Journal of Organic Chemistry,Synthesis of the Glycopeptidolipid of <i>Mycobacterium </i><i>a</i><i>vium </i>Serovar 4:  First Example of a Fully Synthetic C-Mycoside GPL,"The preparation of the glycopeptidolipid (GPL) present in the cell wall of Mycobacterium aviumSerovar 4, namely 3,4-di-O-Me-alpha-L-Rhap-(1-->1)[R-C(21)H(43)CH(OH)CH(2)CO-D-Phe-[4-O-Me-alpha-L-Rhap-(1-->4)-2-O-Me-alpha-L-Fucp-(1-->3)-alpha-L-Rhap-(1-->2)-6-deoxy-alpha-L-Talp-(1-->3)]-D-allo-Thr-D-Ala-L-Alaol] (1), is described. The synthesis was based on the disconnection of the final structure into four building blocks, an L-rhamnosyl pseudodipeptide, a 6-deoxy-L-talosyl dipeptide, a trisaccharide donor, and a 3-hydroxyalkanoic acid. The key steps are the creation of the glycosidic linkage between the trisaccharide donor, used as a pentenyl glycoside, and the 6-deoxy-L-talose unit of an appropriate D-Phe-O-(6-deoxy-L-talosyl)-D-allo-Thr derivative and the final coupling of the two glycodipeptide fragments. Pentenyl glycosides were shown to provide useful donors in several glycosylation steps. This work constitutes the first synthesis of the full structure of a so-called ""polar mycoside C"" GPL.",10.1021/jo030304e,2004-03-05,0.5957737132980544
Journal of Organic Chemistry,Zn(II)-Mediated Alkynylation−Cyclization of <i>o</i>-Trifluoroacetyl Anilines:  One-Pot Synthesis of 4-Trifluoromethyl-Substituted Quinoline Derivatives,A novel efficient route to 4-trifluoromethyl-substituted quinoline derivatives through the Zn(II)-mediated alkynylation-cyclization of o-trifluoroacetyl anilines is described.,10.1021/jo0204606,2002-11-23,0.5957709507612909
Organic Letters,"Studies on the Synthesis of Tedanolide:  Synthesis of the C(5)−C(21) Segment via a Highly Stereoselective Fragment Assembly Aldol Reaction of a Chiral β,γ-Unsaturated Methyl Ketone","[formula: see text] A highly diastereoselective synthesis of 3, corresponding to the C(5)-C(21) segment of tedanolide, has been accomplished by a route utilizing the aldol reaction of aldehyde 4 and the beta,gamma-unsaturated methyl ketone 5.",10.1021/ol990572s,1999-05-24,0.5957700468604975
Synthesis,A New and Improved Synthesis of the Precursor of the Hypoxia Marker [¹8F]-FMISO,All articles of this category (opens in new window),10.1055/s-0030-1258269,2010-09-28,0.595769390796829
European Journal of Organic Chemistry,Formal Total Synthesis of Brevisamide by Using a Tandem Isomerization/C–O and C–C Bond Formation Reaction,"Abstract A highly stereoselective formal total synthesis of brevisamide is described that proceeds through a convergent pathway and utilizes our own tandem isomerization/C–O and C–C bond formation reaction as the key step to construct the trans ‐2,6‐disubstituted dihydropyran ring system. Other significant reactions in this synthesis include an iodolactonization, a Crimmins‐modified “non‐Evans” syn aldol reaction, and a Horner–Wadsworth–Emmons olefination.",10.1002/ejoc.201600142,2016-04-04,0.5957672882382256
European Journal of Organic Chemistry,"A New Strategy for the Asymmetric Synthesis of 1,3-Oxathiolane-Based Nucleoside Analogues",A ready asymmetric synthesis of 3′-oxathionucleosides has been accomplished in three main steps from benzoyloxyethanal. The synthesis is characterized by high overall yield and considerable enantiomeric excesses. It represents a general synthetic path to prepare a wide range of heterosubstituted sulfur-containing nucleoside analogues.,10.1002/(sici)1099-0690(199906)1999:6<1455::aid-ejoc1455>3.0.co;2-v,1999-06-01,0.5957615215050454
Synthesis,"A Facile Access to Novel (5+5) Annellated Heterocycles: Synthesis of a Furopyrrole, an Imidazoimidazole and a Pyrroloimidazole","We describe the synthesis of an ethyl 3-aryl-6H-furo[2,3-b]pyrrole-5-carboxylate 2, a 5-aryl-1H-imidazo[1,2-a]imidazole 3, and an ethyl-1-aryl-1,4-dihydropyrrolo[2,3-d]imidazole-5-carboxylate 4 as new hinge-binding motifs for PI3K kinase inhibitors. A key reaction for the formation of 2 and 4 is the Hemmetsberger–Knittel cyclization of acryloazides. The core of 3 is accessible through reaction of an α-haloketone with 2-aminoimidazole.",10.1055/s-0039-1689916,2019-06-25,0.59575610914121
Organic Letters,Asymmetric Total Synthesis of (−)-Callystatin A Employing the SAMP/RAMP Hydrazone Alkylation Methodology,"[structure: see text] The asymmetric total synthesis of (-)-callystatin A has been achieved. The key steps generating the stereogenic centers rely on the asymmetric alpha-alkylation of aldehydes or ketones exploiting the SAMP/RAMP hydrazone alkylation methodology, as well as an enzymatic enantioselective reduction of a 3,5-dioxocarboxylate. For the construction of the alkene moieties, highly selective Wittig or Horner-Wadsworth-Emmons reactions were employed.",10.1021/ol0256116,2002-02-16,0.5957514115602748
European Journal of Organic Chemistry,A Flexible Route Towards Five‐Membered Ring Imino Sugars and Their Novel 2‐Deoxy‐2‐fluoro Analogues,"Abstract A flexible route towards five‐membered ring imino sugars starting from a chiral α,β‐epoxy aldehyde has been developed. The approach relies on the use of the versatile epoxyamine intermediate 4 , from which regiocontrolled epoxide opening affords diastereoselective access to trisubstituted pyrrolidines. Described here is the nucleophilic attack at C‐2 of the pivotal epoxypyrrolidine 10 , leading to the biologically relevant imino sugars 1,4‐dideoxy‐1,4‐imino‐ D ‐arabinitol ( 2 ) and 1,4‐dideoxy‐1,4‐imino‐ L ‐galactitol ( 3 ) as well as their novel 2‐deoxy‐2‐fluoro analogues, after oxidative manipulation of the vinyl moiety. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2003)",10.1002/ejoc.200300163,2003-07-15,0.59574938478202
Synthesis,An Efficient Route to N-Monosubstituted Guanidino-Lactams,"A small library of guanidino-lactams were synthesized in four steps and good overall yields by following the routes: preparation of guanylating agents, synthesis of protected guanidino-acids, cyclization to fully protected guanidino-lactams, and deprotection to the target compounds. The guanidino-lactams were assayed as antimicrobials on E. coli showing no significant antibiotic activity.",10.1055/s-0034-1378845,2015-06-25,0.5957478655492805
Journal of Organic Chemistry,A New Synthetic Route to Protected α-Hydrazinoesters in High Optical Purity Using the Mitsunobu Protocol,International audience,10.1021/jo005696t,2001-03-15,0.5957438616752664
Organic Letters,Toward the Total Synthesis of Natural Peloruside A:  Stereoselective Synthesis of the Backbone of the Core,[reaction: see text] An asymmetric synthesis of the backbone of the core of natural peloruside A is described. Key elements include reiterative application of enantioselective allylation to establish the stereochemistry of the backbone and a double asymmetric aldol reaction to successfully couple two fragments.,10.1021/ol036058a,2003-12-13,0.5957371041645056
Journal of Organic Chemistry,Synthesis of the C1‘−C11‘ Oxazole-Containing Side Chain of Leucascandrolide A. Application of a Sonogashira Cross-Coupling,"An efficient, convergent synthesis of the C1'-C11' side chain (3) of leucascandrolide A (1) has been achieved. The key bond connection is made through the use of a palladium(0)-catalyzed Sonogashira cross-coupling between trifloyl oxazole (4) and alkynylmetal species (5).",10.1021/jo0204000,2002-08-22,0.5957344182446647
Tetrahedron,Asymmetric synthesis of axially chiral 1-(2′-methyl-3′-indenyl)naphthalenes via prototropic rearrangements of stable rotamers of 1-(2′-methyl-1′-indenyl)naphthalenes,,10.1016/s0040-4039(98)01369-0,1998-09-01,0.5957247685365699
Tetrahedron,Conversion of pravastatin into an advanced intermediate for the synthesis of the HMG-CoA reductase inhibitor BB-476,,10.1016/j.tetlet.2009.10.080,2009-10-23,0.5957219468416322
Tetrahedron,Asymmetric synthesis with chiral hydrogenolysable amines. A short synthesis of (−) isoretronecanol,,10.1016/0040-4039(93)85017-q,1993-03-01,0.5957165216419658
Organic Process Research & Development,Rapid Multikilogram Scale-Up of Di- and Trifluoromethoxy Proline Derivatives,"This report describes the synthesis, development, and scale-up (up to 10 kg) of di- and trifluoromethoxy prolines, key fragments evaluated in the development of potential antiviral SARS-CoV2 M pro inhibitors. We first demonstrate a scalable route to 1- tert -butyl 2-methyl (2 S,4 R )-4-(difluoromethoxy)pyrrolidine-1,2-dicarboxylate employing a Cu-catalyzed difluoromethylation of alcohols using 2,2-difluoro-2-(fluorosulfonyl)acetic acid. We then demonstrate the optimization and scale-up of challenging 1- tert -butyl 2-methyl (2 S,4 R )-4-(trifluoromethoxy)pyrrolidine-1,2-dicarboxylate through silver-mediated oxidative trifluoromethylation of the corresponding alcohol. Finally, we report on the oxidative fluoro-desulfurization of xanthates as a potentially scalable route to access chiral aliphatic trifluoromethoxy ethers.",10.1021/acs.oprd.3c00493,2024-03-11,0.5957064479483067
Journal of Organic Chemistry,"Route to Benzo- and Pyrido-Fused 1,2,4-Triazinyl Radicals via <i>N</i>′-(Het)aryl-<i>N</i>′-[2-nitro(het)aryl]hydrazides","A two-step route to 1,3-disubstituted benzo- and pyrido-fused 1,2,4-triazinyl radicals is presented. The route involves the N'-(2-nitroarylation) of easily prepared N'-(het)arylhydrazides via nucleophilic aromatic substitution of 1-halo-2-nitroarenes, which in most cases gives N'-(het)aryl-N'-[2-nitro(het)aryl]hydrazides in good yields. Mild reduction of the nitro group followed by an acid-mediated cyclodehydration gives the fused triazines, which upon alkali treatment afford the desired radicals. Fifteen examples of radicals are presented bearing a range of substituents at N-1, C-3, and C-7, including the pyrid-2-yl and 8-aza analogues. This route to the N'-(het)aryl-N'-[2-nitro(het)aryl]hydrazides, which works well with benzo- and picolinohydrazides, required a modification for aceto- and trifluoroacetohydrazides that involved a multistep synthesis of asymmetrically 1,1-diaryl-substituted hydrazines.",10.1021/jo402481t,2013-12-12,0.5957016008249815
Synlett,"A Succinct Asymmetric Synthesis of (2<i>S</i>,3<i>R</i>)-2-Methyl-3-aminopentanoic Acid Hydrochloride","All articles of this category The highly stereoselective conjugate addition of lithium ( R )-(α-methylbenzyl)benzylamide ( R )- 2 to tert -butyl ( E )-2-methyl-2-pentenoate 3 affords a straightforward synthesis of (2 S ,3 R )-2-methyl-3-aminopentanoic acid 1 as its hydrochloride salt 5 .",10.1055/s-1994-22760,1994-01-01,0.5956993446354575
Angewandte Chemie International Edition,Concise Synthesis of (+)‐[<sup>13</sup>C<sub>4</sub>]‐Anatoxin‐a by Dynamic Kinetic Resolution of a Cyclic Iminium Ion,"Abstract An asymmetric total synthesis of [ 13 C 4 ]‐anatoxin‐a ([ 13 C 4 ]‐ 1 ) has been developed from commercially available ethyl [ 13 C 4 ]‐acetoacetate ([ 13 C 4 ]‐ 15 ). The unique requirements associated with isotope incorporation inspired a new, robust, and highly scalable route, providing access to 0.110 g of this internal standard for use in the detection and precise quantification of anatoxin‐a in freshwater. A highlight of the synthesis is a method that leverages a cyclic iminium ion racemization to achieve dynamic kinetic resolution in an enantioselective Morita–Baylis–Hillman (MBH) cyclization.",10.1002/anie.202004464,2020-04-18,0.5956985280495678
Journal of the American Chemical Society,Enantioselective Total Synthesis of Isoedunol and β-Araneosene Featuring Unconventional Strategy and Methodology,"A new synthetic strategy for the enantioselective synthesis of members of the dolabellane family of marine natural products has been demonstrated for the specific examples beta-araneosene and isoedunol (1 and 2, respectively) by the pathway outlined in Scheme 1. Key steps include (1) diastereoselective alkylation of Seebach's chiral lactate acetal (6) by the iodide derived from 5; (2) Kulinkovich ethylenation of ester 9 to form the cyclopropanol 10; (3) ring expansion of 10 to form 11; (4) pinacol cyclization of keto aldehyde 12 to form 13a; (5) rearrangement of 13b to 14; (6) propenylation of 14 to 2; and (7) reductive pi-transposition to form 1.",10.1021/ja055137+,2005-09-15,0.5956978684046631
Tetrahedron,"An efficient synthesis of N-protected threo (2R,3S)-3-amino-1,2-epoxy phenylbutane",,10.1016/j.tetlet.2005.06.134,2005-07-18,0.5956967643892823
Tetrahedron,"A novel and effective route to 1,3-oxazolidine derivatives. Palladium-catalyzed regioselective [3 + 2] cycloaddition of vinylic oxiranes with imines",,10.1016/s0040-4039(99)80110-5,1999-01-01,0.5956904837788739
Tetrahedron,"Oxazoline formation via a palladium-catalyzed cyclization: A direct, stereoselective approach to cis-5-amino-2-cyclopenten-1-ol derivatives",Alanyl substituted 4-amino-2-cyclopenten-1-yl acetates were obtained optically pure in three steps from cyclopentadiene. The Pd0 catalyzed cyclization of these allylic acetates was studied using protected and unprotected derivatives. A novel oxazoline synthesis was developed and its utility was demonstrated by the preparation of a cis-5-amino-2-cyclopenten-1-ol derivative.,10.1016/0040-4039(95)00465-o,1995-04-01,0.5956855019906998
Synlett,"A Novel 1,3-Central-to-Axial Chirality Induction Approach to Cyclooctadiene Lignans","The catalytic asymmetric synthesis of an axially chiral biaryl, potentially useful intermediate in the synthesis of dibenzocyclooctadiene lignans, has been performed. The key step consisted of a diastereoselective Suzuki coupling between a chiral benzylic alcohol and a sterically hindered boronic ester. The 1,3-induction from the benzylic stereocenter to the biaryl axis proceeded with very good diastereoselectivity.",10.1055/s-2003-42039,2003-01-01,0.5956849902571993
Synthesis,Complementary Synthetic Approaches to Constitutionally Diverse N-Aminoalkylated Isoindolinones: Application to the Synthesis of Falipamil and 5-HT1A Receptor Ligand Analogues,Different synthetic approaches for the elaboration of poly and diversely substituted isoindolinones tailed with constitutionally diverse aminoalkylated chains have been developed. The key step is based upon the preliminary assembly of the isoindoli­none template equipped with hydroxyalkyl appendages. Subsequent manipulation of the terminal hydroxy functionality afforded the targeted compounds and the synthetic utility of these approaches has been emphasized by the synthesis of the bradycardic agent falipamil and 5-HT1A receptor ligand analogues.,10.1055/s-0028-1088048,2009-04-14,0.5956728749727552
Tetrahedron,Synthesis o an 8-deaza analog of the intermediate in the thymidylate synthetase reaction,,10.1016/s0040-4039(00)87125-7,1982-01-01,0.5956678844219546
Tetrahedron,Total synthesis of the C37C45 F-ring fragment of spongistatins,,10.1016/s0040-4039(97)10817-6,1998-03-01,0.5956670150654314
Tetrahedron,Synthetic studies toward marine toxic polyethers (2) synthesis of the B-segment of okadaic acid and coupling with the C-segment,,10.1016/s0040-4039(01)91116-5,1984-01-01,0.5956658234772774
Angewandte Chemie International Edition,Integrated Chemoenzymatic Synthesis of the mRNA Vaccine Building Block <i>N</i> <sup>1</sup> ‐Methylpseudouridine Triphosphate,"Abstract Pseudouridine‐5′‐triphosphate (ΨTP) and its N 1 ‐methylated derivative (m 1 ΨTP) are critical monomer building blocks of mRNA therapeutics, yet efficient, scalable methods of their synthesis from readily accessible substrates remain underdeveloped. m 1 ΨTP is a major cost factor of production of the current COVID‐19 vaccines. We herein report a notably atom‐economic and high‐yielding biocatalytic route toward ΨTP and present two chemoenzymatic routes for producing m 1 ΨTP at ∼200 mg scale of isolated compound. Biocatalytic cascade rearrangement of uridine delivered ΨMP or Ψ in high yields. Acetonide‐protected ΨMP was selectively N 1 ‐methylated using dimethyl sulfate and subsequently converted to the triphosphate through efficient kinase cascade reaction. Saccharomyces cerevisiae uridine 5′‐monophosphate kinase was shown for ATP‐dependent phosphorylation of m 1 ΨMP to m 1 ΨDP and m 1 ΨTP synthesis was catalyzed by Escherichia coli acetate kinase which also served to regenerate ATP by acetyl phosphate. Benchmarked against chemical route converting the enzymatically produced Ψ into m 1 ΨTP, the novel chemoenzymatic route from ΨMP offered improved metrics of reaction efficiency and sustainability. The synthetic ΨTP and m 1 ΨTP replaced UTP for mRNA synthesis by in vitro transcription. Overall, this study shows the productive integration of chemical methylation with enzymatic cascade reactions for C─C coupling and phosphorylation toward an efficient preparation of m 1 ΨTP.",10.1002/anie.202506330,2025-05-27,0.5956612036849845
Synlett,Three-Step Synthesis of 3-Aminoindole-2-carboxylate-Conjugated 2-Amino-6-chloropyrimidines and Their Anticancer Activity,"Abstract The synthesis of novel indolo-pyrimidine derivatives is of considerable interest due to the combined pharmacological benefits of indole and pyrimidine cores, particularly for anticancer applications. In this study, we report an efficient three-step synthesis of a novel series of 3-amino-1-(2-amino-6-chloropyrimidin-4-yl)-1H-indole-2-carboxylate derivatives, employing specific bases and solvents, in high yields. The synthetic route proceeds through key intermediates: 2-aminopyrimidine-benzonitriles and 2-aminopyrimidine-glycinates, culminating in the formation of 2-aminopyrimidine-indole hybrids. Biological evaluation of the products against three human cancer cell lines and one normal cell line revealed moderate anticancer activity and minimal toxicity, highlighting their potential as promising leads for further anticancer drug development.",10.1055/a-2698-3056,2025-09-09,0.595653727948333
Tetrahedron,Palladium-catalyzed intramolecular allylic alkylation of α-sulfinyl carbanions: a new asymmetric route to enantiopure γ-lactams,,10.1016/j.tetlet.2010.01.012,2010-01-12,0.5956530382137742
Synlett,Enzyme and Gold Catalysis: A New Enantioselective Entry into Functionalized 4-Hydroxy-2-pyrrolines,A new route toward functionalized pyrrolines starting from acetylenic aldehydes was developed. Key steps involved a ­hydroxynitrile lyase catalyzed asymmetric hydrocyanation of acetylenic aldehydes and a gold-catalyzed cyclization of substituted acetylene-containing amino alcohols.,10.1055/s-0033-1340251,2013-11-13,0.595650516672516
European Journal of Organic Chemistry,Synthesis and Post‐Resolution Modification of New Axially Chiral Ligands for Asymmetric Catalysis,"Abstract The synthesis of four new members of the Quinazolinap series of ligands is described. Three of these ligands were prepared by post‐resolution modification of the known ligand ( R )‐7‐chloro‐2‐isopropyl‐Quinazolinap, a new approach which offers an expedient route to a range of enantiopure ligands as it precludes the need for resolution of each ligand prepared. The remaining ligand, 7‐chloro‐2‐methyl‐Quinazolinap, was prepared in a seven‐step synthetic sequence incorporating palladium‐ and nickel‐catalyzed transformations as the key steps. A diastereomerically pure palladacycle of this ligand was characterised by X‐ray crystallography. ( R )‐7‐Chloro‐2‐isopropyl‐Quinazolinap was applied to the rhodium‐catalyzed hydroboration of vinylarenes with regioselectivities of up to &gt; 99:1 and ee values of up to 68 %. Each of the Quinazolinap ligands prepared were applied to the palladium‐catalyzed allylic alkylation of 1,3‐diphenylprop‐2‐enyl acetate resulting in conversions of up to 100 % and ee values of up to 85 %. Solution‐phase NMR studies on a palladium complex of one of the ligands provided a rationale for the sense of asymmetric induction.",10.1002/ejoc.201000794,2010-09-14,0.595642835142111
Angewandte Chemie International Edition,An Enantioselective Biomimetic Total Synthesis of (−)‐Siccanin,"A convergent asymmetric synthesis of the clinically important antifungal agent (−)-siccanin (1) mimics the proposed biosynthetic pathway. A Pd-catalyzed asymmetric allylic alkylation was used to establish the stereochemistry, and sequential radical processes (a TiIII-promoted cyclization followed by diacetoxyiodobenzene-promoted tetrahydrofuran formation) led to the completion of the first asymmetric synthesis of 1.",10.1002/anie.200351868,2003-08-22,0.5956360047000427
Organic Process Research & Development,Integrating Process Safety Consideration to Enhance Route Development and Optimization,"In the development of a route to an advanced intermediate, methyl 1-amino-7-(benzyloxy)thieno[3,2- f ]quinoline-2-carboxylate ( 1 ), significant safety hazards were identified in both the tandem cyanation/nitro reduction and tert -butyl nitrite (TBN)-mediated Sandmeyer reactions. The cyanation exhibited substantial thermal accumulation and severe decomposition due to the use of dimethyl sulfoxide (DMSO) as a solvent, resulting in a Criticality 5 risk level according to Stoessel. Similarly, the TBN-mediated Sandmeyer reaction showed strong decomposition, further compounding the safety concerns. In response to these hazards, a new route was developed. Process safety evaluations played a crucial role in guiding the development of this safer route, which was successfully implemented, leading to substantial improvements in safety, yield, and overall efficiency. This success underscores the critical importance of integrating process safety evaluation during the early stages of process and route development.",10.1021/acs.oprd.5c00274,2025-10-14,0.5956334181734912
Journal of Organic Chemistry,"Synthesis of Isagarin, a New Type of Tetracyclic Naphthoquinone from <i>Pentas longiflora</i>","Isagarin ( 1 ) was synthesized in four steps from 1,4-dimethoxynaphthaldehyde ( 4 ). The key intermediate 2-(1,2-dihydroxyethyl)-1,4-naphthoquinone ( 3 ) was found to react with acylated pyridinium ylides to afford, after spontaneous intramolecular condensation, the desired natural product isagarin ( 1 ). Depending on the type of acylated pyridinium ylides, different types of new pyranonaphthoquinone derivatives were obtained.",10.1021/jo9813888,1998-12-29,0.5956267858303659
Journal of the American Chemical Society,Enantioselective Synthesis of Chiral Piperidines via the Stepwise Dearomatization/Borylation of Pyridines,"We have developed a novel approach for the synthesis of enantioenriched 3-boryl-tetrahydropyridines via the Cu(I)-catalyzed regio-, diastereo-, and enantioselective protoborylation of 1,2-dihydropyridines, which were obtained by the partial reduction of the pyridine derivatives. This dearomatization/enantioselective borylation stepwise strategy provides facile access to chiral piperidines together with the stereospecific transformation of a stereogenic C-B bond from readily available starting materials. Furthermore, the utility of this method is demonstrated for the concise synthesis of the antidepressant drug (-)-paroxetine. A theoretical study of the reaction mechanism is also described.",10.1021/jacs.6b01375,2016-03-11,0.5956255316177969
European Journal of Organic Chemistry,A Concise Total Synthesis of the Stereoisomers of (–)‐Pochonicine,"Abstract A concise total synthesis of the four stereoisomers of (–)‐pochonicine was undertaken. The key steps of the synthesis involved chemoselective debenzylation of the primary benzyloxy group and an unprecedented Na–Hg‐mediated concomitant N ‐detosylative intramolecular epoxide ring‐opening reaction. Notably, additional steps for the protection of other functional groups were not required. Glycosidase inhibition studies revealed that these compounds are inhibitors of β‐ N ‐acetylglucosaminidase with IC 50 values in the sub‐millimolar range.",10.1002/ejoc.201501413,2016-01-15,0.5956248318416256
Organic Letters,Synthesis of Spirotricyclic Core of Bonnadiene,"We herein describe a new approach for the efficient synthesis of the tricyclic core of diterpene bonnadiene. The synthetically challenging and unusual [6-7-5] spirotricyclic skeleton including the all-carbon quaternary stereocenter, was installed diastereoselectively via a type II [5 + 2] cycloaddition, followed by a unique vinylogous semipinacol rearrangement. The described chemistry demonstrates the feasibility of making the [6-7-5] spirotricyclic skeleton of the final product from the strained bridged [7-8-5] ring system.",10.1021/acs.orglett.3c00142,2023-02-09,0.5956183883257534
Organic Letters,"Enantioselective Access to 2,7-Cis-Disubstituted Oxepanes:  Formal Synthesis of (+)-Isolaurepan","[reaction: see text] The asymmetric synthesis of 2,7-cis-disubstituted oxepanes bearing a sulfoxide is achieved from commercially available precursors in only five steps. The key step is the highly diastereoselective Et3SiH/TMSOTf-promoted reductive cyclization of enantiopure hydroxysulfinyl aryl or alkyl ketones.",10.1021/ol036299i,2003-12-31,0.5956149373301373
Tetrahedron,Synthesis of 17α-4-amino- and 4-iodophenylestradiols,,10.1016/s0040-4039(00)01238-7,2000-10-01,0.5956146123996728
Tetrahedron,The synthesis of 2-amino-2-deoxysugars from acetylated glycals,,10.1016/s0040-4039(00)90168-0,1965-01-01,0.5956146123996728
Tetrahedron,Synthesis of 3-arylquinazolin-4(3H)-imines from 2-amino-N′-arylbenzamidines and triethyl orthoformate,,10.1016/j.tetlet.2015.01.133,2015-01-24,0.5956146123996728
Tetrahedron,Synthesis of a 2-amino aziridine,,10.1016/s0040-4039(01)98634-4,1970-01-01,0.5956146123996728
Tetrahedron,Synthesis of N-amino- and N-nitramino-nitroimidazoles,,10.1016/j.tetlet.2009.11.046,2009-11-16,0.5956146123996728
Tetrahedron,Synthesis of 4-arylaminoquinazolines via 2-amino-N-arylbenzamidines,,10.1016/s0040-4039(97)10864-4,1998-03-01,0.5956146123996728
Tetrahedron,"Conformationally locked nucleosides. Synthesis and stereochemical assignments of 3′-N,5′-C-bridged 3′-amino-3′-deoxythymidines",,10.1016/s0040-4039(99)01205-8,1999-08-01,0.5956146123996728
Tetrahedron,The synthesis of 3-amino-5-arylisothiazoles from propynenitriles,,10.1016/j.tetlet.2018.01.042,2018-01-31,0.5956146123996728
Synthesis,Synthesis and Incorporation into Oligodeoxynucleotides of Carbocyclic exo-Amino Nucleosides,,10.1055/s-0031-1289737,2012-03-02,0.5956146123996728
Journal of Organic Chemistry,Asymmetric Synthesis of Homocitric Acid Lactone,"A short, diastereoselective synthesis of homocitric acid lactone is described. The key step is a bioinspired aldol addition to set the stereogenic center in an intermediate that requires only modest oxidation state manipulation to complete the synthesis. This approach enables rapid generation of isotopomers in which carbon and hydrogen can be replaced by heavier nuclei at nearly every position.",10.1021/acs.joc.6b01997,2016-09-30,0.5956115492013179
Tetrahedron,"Stereo-controlled synthesis of analogs of peumusolide A, NES non-antagonistic inhibitor for nuclear export of MEK",,10.1016/j.tetlet.2010.04.027,2010-04-14,0.595609681088425
Synlett,Concise Total Asymmetric Synthesis of (S)-2-Phenylpiperidin-3-one,"Starting from readily available dihydropyridinones, we have developed the first synthesis of (S)-2-phenylpiperidin-3-one. While the scaffold appears relatively common, even in its racemic form, this original product can be considered as a potential precursor of substance P antagonist.",10.1055/s-0029-1218359,2009-11-11,0.5956071301734248
Synthesis,A Short Synthesis of the Bacterial Pigments Violacein and Deoxyviolacein,A concise synthesis of the bacterial pigments deoxyviolacein (1a) and violacein (1b) is described in which two indole units are attached stepwise to the central pyrrolinone ring.,10.1055/s-2001-12776,2001-01-01,0.5955968605992221
European Journal of Organic Chemistry,"Short Synthesis of Vesperal [(S)-10-Oxoisopiperitenone], the Female Sex Pheromone of the Longhorn Beetle (Vesperus xatarti), and of Its Enantiomer","Vesperal [(S)-10-oxoisopiperitenone, 1], the female sex pheromone of the longhorn beetle (Vesperus xatarti), was synthesized from (R)-limonene (3) in 6% overall yield (6 steps). The non-natural (R)-vesperal was also prepared from (S)-limonene.",10.1002/1099-0690(200011)2000:22<3783::aid-ejoc3783>3.0.co;2-o,2000-11-01,0.5955954028721167
Synlett,Facile and Efficient Synthesis of Fluoroprostacyclin Analogs,All articles of this category New and facile synthesis of chemically stable 7-fluoroprostacyclins ( 1 ) from commercially available methylenecyclopentanones 2 is described. Construction of key 7-hydroxyprostaglandin skeletons has been efficiently accomplished by the coupling of acetylenic acid with triethylsiloxycyclopentane carbaldehydes 4 under mild conditions. fluoroprostacyclin - methylenecyclopentanone - lithiation of acetylenic acid - stereospecific fluorination,10.1055/s-1995-4945,1995-03-01,0.5955930936289925
Organic Letters,Asymmetric Construction of the Tricyclic Core Structure of Prostratin,A synthetic study on asymmetric construction of the tricyclic core structure of prostratin is developed through a convergent strategy. Critical to the success of this endeavor is the strategic use of intermolecular allylic nucleophilic substitution to assemble the ring A system and ring C system while utilizing intramolecular nucleophilic addition to close the seven-membered ring.,10.1021/acs.orglett.4c03606,2025-02-07,0.5955914298475081
Journal of Organic Chemistry,"An Expeditious, High-Yielding Construction of the Food Aroma Compounds 6-Acetyl-1,2,3,4-tetrahydropyridine and 2-Acetyl-1-pyrroline","[reaction: see text] The key compound responsible for the aroma of bread, 6-acetyl-1,2,3,4-tetrahydropyridine (1), has been constructed in an efficient three-step procedure from 2-piperidone in an overall yield of 56%. Compound 1 was liberated in the final step under basic conditions. A related synthetic route produced 2-acetyl-1-pyrroline (2), the principal component of cooked rice, in 10% overall yield.",10.1021/jo051940a,2005-11-30,0.5955858775124534
Organic Letters,A General Approach to Cyathin Diterpenes. Total Synthesis of Allocyathin B<sub>3</sub>,"[reaction: see text] The synthesis of allocyathin B(3) from an advanced intermediate possessing the ring system and relative stereochemistry but lacking the isopropyl and hydroxymethyl groups is reported. The isopropyl group was introduced by radical cyclization of a methyl propargyl acetal of an alpha-bromo ketone, and the hydroxymethyl group was generated by Pd-catalyzed carbonylation of a vinyl triflate. The route provides functionalized intermediates that could allow access to more complex members of the cyathin family of diterpenes.",10.1021/ol006026c,2000-06-17,0.5955810536053424
Organic Letters,Formal Synthesis of (+)-Discodermolide,[structure: see text] Herein we report the formal total synthesis of (+)-discodermolide in 21 steps (longest linear sequence) from commercially available Roche ester. This synthesis features the assembly of C(9-18) and C(19-24) fragments via a metal-chelated aldol coupling reaction.,10.1021/ol034186t,2003-03-21,0.5955737422929912
Tetrahedron,"Short synthesis of (3S,6S,9S)-2-oxo-3-(N-Boc-amino)-1-azabicyclo[4.3.0]nonane-9-carboxylic acid methyl ester: Tandem cyclization protocol",,10.1016/s0040-4039(97)01492-5,1997-09-01,0.5955676782662651
Journal of Organic Chemistry,Total Synthesis of Desoxoprosophylline:  Application of a Lactam-Derived Enol Triflate to Natural Product Synthesis,"The total synthesis of desoxoprosophylline 1 from a piperidinone-derived enol triflate 8 has been realized and is one of the first applications of such lactam-derived triflates to natural product synthesis. Palladium-catalyzed methoxycarbonylation of 8 followed by 1,2-reduction and protection introduces the required C2 hydroxymethyl group, affording 10 . The C3 hydroxy function is stereoselectively added by a novel N -tosylenamide hydroboration (de 88%), and the final C6 dodecyl chain is incorporated with complete stereocontrol, in a single step, via an N -tosyliminium ion−allylsilane coupling. Deprotection gives the natural product in an efficient 7.5% yield over nine steps.",10.1021/jo962347j,1997-05-01,0.5955561636384387
Angewandte Chemie International Edition,Total Synthesis of Neooxazolomycin,"Two sides to the story: Neooxazolomycin, a member of the oxazolomycin family of antibiotics, was synthesized in naturally occurring form by a convergent approach. This highly stereoselective strategy consists of a Tamao hydrosilylation, palladium-catalyzed enolate alkenylation, dihydroxylation accompanied by lactonization, and a Nozaki–Hiyama–Kishi reaction to construct the right-hand segment as well as an improved route to the left-hand segment.",10.1002/anie.200702229,2007-07-31,0.5955503706691799
Tetrahedron,Synthesis of oligonucleotide inhibitor of protein synthesis: pppA2′p5′A2′p5′A,,10.1016/s0040-4039(01)86652-1,1979-01-01,0.595548365444922
Synthesis,The Synthesis and F-18 Labeling of a Cinacalcet Analogue Based on α-(Monofluoromethyl)arylmethylamine Structure,"Abstract The fluorine-containing drug Cinacalcet is the only oral calcimimetic agent for the management of hyperparathyroidism in China and targets calcium sensitive receptor (CaSR) in organ tissues. The monofluoromethyl (CH2F) motif, found in many drug molecules and bioactive molecules, is particularly valuable as the CH2F functional group can mimic the methyl (CH3) motif frequently encountered in bioactive molecules. Replacing CH3 group of Cinacalcet with CH2F group will both bring new opportunities for the development of Cinacalcet generic drugs and provide a new option for the F-18 labeling synthesis of Cinacalcet. A Cinacalcet analogue has been successfully synthesized using commercial 2-amino-2-(naphthalen-1-yl)ethan-1-ol and 3-(3-(trifluoromethyl)phenyl)propanal as raw materials in a total yield of 24% in five steps and achieved the F-18 labeling synthesis of this analogue. This strategy is simple and efficient, paving the way for PET imaging of CaSR related diseases and inspiring development of new drugs based on Cinacalcet­.",10.1055/s-0043-1775415,2024-11-04,0.5955407217199353
Organic Letters,A Scalable Route to Trisubstituted (<i>E</i>)-Vinyl Bromides,"An effective, readily scalable two-step synthesis of trisubstituted (E)-vinyl bromides involving bromination of alpha,beta-unsaturated lactones followed by hydrolytic fragmentation has been developed. Several trisubstituted (E)-vinyl bromides, including multigram quantities of (+)-(E)-4-bromo-2-methyl-3-pentenol, a synthetic intermediate required for the C(8)-C(11) moieties of (+)-tedanolide (1) and (+)-13-deoxytedanolide (2), illustrate the utility of this protocol. [reaction: see text]",10.1021/ol051376q,2005-07-15,0.5955317784798295
Journal of Organic Chemistry,"Preparation of New Chiral Building Blocks:  Highly Enantioselective Reduction of Prochiral 1,3-Cycloalkanediones Possessing a Methyl Group and a Protected Hydroxymethyl Group at Their C2 Position with Baker's Yeast or CBS Catalyst","Highly enantioselective reduction of five-, six-, seven-, and eight-membered prochiral 1,3-cycloalkanediones possessing a methyl group and a protected hydroxymethyl group at their C2 position with baker's yeast or CBS catalyst and a new efficient and general method for preparing the 1,3-cycloalkanediones have been developed. These baker's yeast mediated reductions were found to produce corresponding ketols with high optical purity (>99% ee) and high yield. All of the prepared ketols and their derivatives, chiral building blocks, have been fully characterized, and their absolute configurations have been determined. These compounds would be useful for the convergent synthesis of complex natural products.",10.1021/jo050349a,2005-05-10,0.5955305093059375
Organic Letters,"Scalable Preparation of 4,4-Disubstituted Six-Membered Cyclic Sulfones","We provide an account of synthetic strategies aimed at the efficient preparation of 4-amino-4-methyltetrahydro-2 H -thiopyran 1,1-dioxide ( 3 ), an important cyclic sulfone building block for medicinal chemistry. A practical and scalable protocol has been developed that readily gives access to the title compound from commercially available and inexpensive starting materials. In addition, this novel approach has enabled the synthesis of various related 4,4-disubstituted cyclic sulfone derivatives that serve as valuable structural motifs for drug discovery.",10.1021/acs.orglett.0c04141,2021-01-08,0.5955221523958825
Synthesis,"A Facile Synthesis of Fragment D of Antibiotic, Nosiheptide","All articles of this category A facile synthesis of the N,O -diprotected fragment of D of Nosiheptide, 2-[(1’ S ,3’ S )-1’-amino-3’-carboxy-3’-hydroxypropyl]thiazole-4-carboxylic acid, from ( S )-2,2-dimethyl-1,3-dioxalane-4-acetaldehyde in 10 steps and 10.6% overall yield, is described. antibiotic - nosiheptide - fragment D - chiral synthon - D-glyceraldehyde",10.1055/s-1995-4117,1995-11-01,0.595518749899235
European Journal of Organic Chemistry,"A Metathesis Route to (+)‐Orientalol F, a Guaiane Sesquiterpene from <i>Alisma Orientalis</i>","The synthesis of (+)‐orientalol F ( 1 ) started with aldehyde 6 , which is available from ( R )‐limonene in two steps. Wittig reaction of 6 with unsaturated ylide 7 to give a tetraene, and subsequent ring‐closing metathesis yielded hydroazulene 4 , selective epoxidation of which gave epoxy ester 3 . After generation of the requisite isopropyl unit and regioselective reductive epoxide opening, the derived dienol 2 was used for the installation of the oxygen bridge through intramolecular oxymercuration followed by oxidative demercuration. The resulting allylic alcohol epimers 15 and 16 were readily converted into the target natural product 1 by oxidation/reduction sequences.",10.1002/ejoc.201601197,2016-10-12,0.5955151949256736
Tetrahedron,Concise route to a series of novel 3-(tetrazol-5-yl)quinoxalin-2(1H)-ones,,10.1016/j.tetlet.2012.01.080,2012-01-31,0.595507674862784
Organic Letters,Total Synthesis of Morusalisin A,"Morusalisin A is a nonclassical mulberry Diels–Alder-type adduct (MDAA) with a unique tricyclic skeleton. Herein, we report the first total synthesis of morusalisin A, accomplished in nine steps with an overall yield of 7.3% from commercially available 2,4,6-trihydroxybenzaldehyde. A key feature of the synthesis is a stereoselective intramolecular Diels–Alder (IMDA) reaction of the benzo-tethered butadienyl cinnamate, which efficiently constructs the tricyclic tetrahydro-6 H -benzo[ c ]chromen-6-one core bearing three contiguous stereogenic centers. The pivotal point of the transformation was the strategic placement of a protecting group ortho on the diene moiety, which not only accommodated the IMDA but also controlled the stereochemical outcome. This study is expected to pave the way for broader application of the IMDA strategies in the synthesis of MDAAs, which have predominantly been accessed through intermolecular DA reactions.",10.1021/acs.orglett.5c03926,2025-10-24,0.5955048631976287
Tetrahedron,Total synthesis of halichondrin b from common sugars: An F-ring intermediate from D-glucose and efficient construction of the C1 to C21 segment,,10.1016/s0040-4039(00)61388-6,1993-12-01,0.5954994266695945
Journal of Organic Chemistry,Synthesis of Some Members of the Hydroxylated Phenanthridone Subclass of the <i>Amaryllidaceae</i> Alkaloid Family,"The total synthesis of several members of the hydroxylated phenanthridone subclass of the Amaryllidaceae alkaloid family has been carried out. (+/-)-Lycoricidine and (+/-)-7-deoxypancratistatin were assembled through a one-pot Stille/intramolecular Diels-Alder cycloaddition cascade to construct the core skeleton. The initially formed [4+2]-cycloadduct undergoes nitrogen-assisted ring opening followed by a deprotonation/reprotonation of the resulting zwitterion to give a rearranged hexahydroindolinone on further heating at 160 degrees C. The stereochemical outcome of the IMDAF cycloaddition has the side arm of the tethered vinyl group oriented exo with respect to the oxygen bridge. The resulting cycloadduct was used for the stereocontrolled installation of the remaining functionality present in the C-ring of the target molecules. Key features of the synthetic strategy include (1) a lithium hydroxide induced tandem hydrolysis/decarboxylation/elimination sequence to introduce the required pi-bond in the C-ring of (+/-)-lycoricidine, and (2) conversion of the initially formed Diels-Alder adduct into an aldehyde intermediate which then undergoes a stereospecific decarbonylation reaction mediated by Wilkinson's catalyst to set the trans-B-C ring junction of (+/-)-7-deoxypancratistatin.",10.1021/jo0626111,2007-03-01,0.5954981642307524
Organic Letters,Synthetic Studies on Halichlorine and Pinnaic Acid. Stereospecific Preparation of the Azaspiro Core Structure,"Halichlorine and pinnaic acid are two novel marine natural products isolated from a Japanese sponge and an Okinawan bivalve, respectively. The unique azaspiro[4.5]decane core structure present in both compounds provides a synthetic challenge. Herein, we describe a synthetic approach to the azaspiro[4.5]decane core structure through an intramolecular [3 + 2] cycloaddition followed by an intramolecular Michael addition and in situ isomerization to afford the azaspirocyclic core structures stereospecifically in 10 steps with 40% overall yield.",10.1021/ol9907668,1999-07-22,0.5954971604153566
European Journal of Organic Chemistry,A Biomimetic Stereoselective Approach to Euolutchuol C and Its Structural Assignment,"Abstract The first stereoselective total synthesis of euolutchuol C using a biomimetic cationic polyene cyclization is demonstrated, and its absolute structure has been established. Four potential stereoisomers of euolutchuol C were synthesized to confirm the structure as an aromatic abietane diterpenoid consisting of 15( S )‐stereogenic center. Asymmetric Sharpless dihydroxylation was employed to construct the chiral epoxide, while CBS‐reduction was utilized for enantiomerically pure benzylic alcohols. A convergent approach is used to synthesize euolutchuol C in seven longest linear steps to give an overall yield of 23 %.",10.1002/ejoc.202300748,2023-09-04,0.5954946768597987
Synlett,Tandem Schiff-Base Formation/Heterocyclization: An Approach to the Synthesis of Fused Pyrazolo–Pyrimidine/Isoxazolo-Pyrimidine Hybrids,"A new synthesis of pyrazolo[4,3-d]pyrimidines and isoxazolo[4,5-d]pyrimidines is described. Key steps in the synthesis involve Stille coupling of 4,6-dichloro-2-phenyl-pyrimidine with tributyl(1-ethoxyvinyl)stannane and tandem Schiff-base formation/heterocyclization of 2,6-di-aryl-5-fluoro-4-acetylpyrimidine with hydrazines or ­hydroxylamine to give pyrazolo[4,3-d]pyrimidines and isoxazolo[4,5-d]pyrimidines, respectively. The position of the fluoro group in the ­pyrimidine ring is important for the success of heterocylization reaction.",10.1055/s-0037-1612081,2019-02-05,0.5954847800254545
Tetrahedron,Alkoxy radicals in organic synthesis. A novel approach to a key intermediate in milbemycin chemistry,,10.1016/s0040-4039(00)73322-3,1994-07-01,0.5954815519788268
Organic Letters,Enantioselective Synthesis of Both Epimers at C-21 in the Proposed Structure of Cytotoxic Macrolide Callyspongiolide,"Both epimers at C-21 in the proposed structure of (+)-callyspongiolide have been synthesized in a convergent and enantioselective manner. The 14-membered macrolide with a sensitive C2-C3 cis-olefin functionality was installed by a Yamaguchi macrolactonization of hydroxyl alkynoic acid followed by hydrogenation over Lindlar's catalyst. The C5 methyl stereocenter was constructed by a ring-closing olefin metathesis followed by addition of methyl cuprate to an α,β-unsaturated δ-lactone. Other key reactions are chiral Corey-Bakshi-Shibata (CBS) reduction and Sonogashira coupling to conjoin the macrocyclic core and side chain.",10.1021/acs.orglett.6b01523,2016-06-22,0.5954707576165098
Synthesis,Asymmetric Synthesis of 2-Substituted Hexahydroquinolin-4-ones Using a Pd-Catalyzed Asymmetric Allylic Amination and Intramolecular Mannich Reaction: Catalytic Asymmetric Synthesis of 2-epi-cis-195A,A novel method of the enantioselective synthesis of 2-substituted hexahydroquinolin-4-ones is described. The method relies on a Pd-catalyzed asymmetric allylic amination using a chiral diaminophosphine oxide (DIAPHOX) preligand and diastereoselective intramolecular Mannich reaction. The developed synthetic method could be applied to the catalytic asymmetric synthesis of (+)-2-epi-cis-195A.,10.1055/s-0030-1260102,2011-07-14,0.5954657973027342
Journal of Organic Chemistry,Streamlined Stereoselective Entry to (−)-Quinagolide and to 3-Substituted Octahydrobenzo[<i>g</i>]-Quinolines,"A very short stereoselective synthesis of enantiomerically pure (3 S, 4a S, 10a R ) - quinagolide has been developed. The key steps involved are a copper-catalyzed regioselective arylation of ( S )-epichlorohydrin with 1,6-dimethoxynaphthalene and a diastereoselective trans -reduction of a cyclic enamine intermediate. The possibility to use both enantiomers of epichlorohydrin and the diastereodivergency found in the reduction process paves the way for a general preparation also in the nonracemic form of chiral trans- fused 3-substituted octahydrobenzo[ g ]quinolines that are privileged structures in medicinal chemistry.",10.1021/acs.joc.3c02681,2024-01-27,0.5954559558089411
Journal of Organic Chemistry,Synthesis of the C<sub>26</sub>−C<sub>32</sub> Oxazole Fragment of Calyculin C:  A Test Case for Oxazole Syntheses,"The synthesis of the C(26)-C(32) oxazole fragment 4 and its C(32) epimer 20 of serine/threonine protein phosphatase PP1 and PP2A inhibitor calyculin C is presented. The syn methyl arrangement in 4 was established through cyclic stereocontrol. Several methods for oxidizing the intermediate oxazolines 18 and 19 to the finished oxazole fragments were explored. The best results were obtained with oxidations proceeding through the corresponding ester enolate when the carbamate NH side chain was temporarily protected with a TMS group, or with CuBr(2)/DBU/HMTA-based oxidations. The finished oxazole fragment 4 was obtained in 21% overall yield, starting from Boc-D-alaninal.",10.1021/jo971167m,1998-01-01,0.5954473639337591
Journal of the American Chemical Society,Application of Ring-Closing Metathesis to the Formal Total Synthesis of (+)−FR900482,"A formal, enantioselective synthesis of the antitumor antibiotic (+)−FR900482 ( 1 ) has been completed using an approach that featured the ring-closing metathesis of the diene 37 to give the key intermediate benzazocine 38 . Although several initial protecting-group strategies unexpectedly failed at various stages of the endeavor, the successful approach to 1 involved the conversion of commercially available 5-nitrovanillin ( 10 ) into the prochiral diol 24 . The manipulations of the residues on the aromatic ring of 10 were straightforward, and the diol array in 24 was introduced by the hydride reduction of the malonate 23, which was in turn prepared by a nucleophilic substitution of the triflate 12 . Adjustment of alcohol-protecting groups to give 27 and refunctionalization of the aromatic nitro group led to the protected N -allylamine 36 . Elaboration of the diol array via a highly stereoselective Grignard addition furnished the diene 37 . Ring-closing metathesis of 37 using the Grubbs catalyst 34 cleanly afforded the benzazocine 38 . A tactic originally conceived for preparing 42 by introduction of the aziridine ring onto 38 was impractical because the iodo cyclization of the allylic tosylcarbamate 39 was neither efficient nor selective to give 40 . Hence, 38 was transformed into 49, which was a key intermediate in Fukuyama's elegant synthesis of racemic FR900482, thereby completing a formal synthesis of the alkaloid. The prochiral diol 24 was enzymatically desymmetrized using Pseudomonas species lipase to give 25 in 94% enantiomeric excess. Inasmuch as subsequent adjustment of the alcohol-protecting groups gave the intermediate 26 (cf the racemic analogue 27 ) in enantiomerically pure form, an enantioselective synthesis of (+)−FR900482 has also been completed in a formal sense.",10.1021/ja0013879,2000-10-24,0.595446175957675
Organic Letters,Formal Synthesis of Lobatamides A and C,"Lobatamides, featuring a unique 15-membered dilactone core, are a family of marine natural products isolated from the tunicate Aplidium lobatum and exhibit inhibitory activity against mammalian vacuolar-type proton pump ATPase (V-ATPase). Herein, we report an alternative route to Sato’s intermediate, achieving formal syntheses of lobatamides A and C. Key steps include the palladium-catalyzed Suzuki–Miyaura coupling reaction to give a salicylic acid derivative containing a trisubstituted ( Z )-olefin and the Nozaki–Hiyama–Takai–Kishi (NHTK) reaction to construct the 15-membered dilactone core.",10.1021/acs.orglett.5c00739,2025-03-17,0.5954410284262966
Tetrahedron,New synthesis of linear furoquinoline alkaloids,,10.1016/j.tetlet.2004.09.041,2004-11-09,0.5954374392089447
Tetrahedron,"The efficient synthesis of (3R,4R,5R)-3-amino-4,5-dimethyl-octanoic acid, a chiral β-amino acid with potent affinity for the α2δ protein",,10.1016/j.tetlet.2008.12.111,2009-01-09,0.5954370032453891
European Journal of Organic Chemistry,Enantioselective Synthesis of (<i>R</i>)‐Homoboroproline from (<i>S</i>)‐Proline Using a Borylation Approach,Abstract ( S )‐Proline was converted through a five‐step sequence into ( R )‐homoboroproline hydrochloride in 29 % overall yield with 97 % ee The key step was the conversion of N ‐Boc iodomethylpyrrolidine into the corresponding pinacol boronate ester by an efficient copper(I)‐catalyzed borylation reaction by using bispinacolatodiboron.,10.1002/ejoc.201200652,2012-06-25,0.5954350761098397
Tetrahedron,The aza-robinson annulation: An application to the synthesis of iso-A58365A,"Annulation of diazomethylvinylketone (4a) with a variety of secondary thiolactams provides a novel route to dihydro-γ-pyridones. This approach has been applied to the synthesis of iso-A58365A (2), the γ-pyridone analog of the ACE inhibitor, A58365A (1).",10.1016/s0040-4039(01)80465-2,1989-01-01,0.595434711920194
Angewandte Chemie International Edition,Asymmetric Synthesis of the Phytopathogen (+)‐Fomannosin,"Three new construction features in one synthesis—for the fused cyclobutene ring, the cyclopentanone, and the functionalized six-membered lactone—characterize the procedure that leads to the natural (+)-enantiomer of the title compound starting with D-glucose. Central to the routing are steps involving organometallic reagents containing ruthenium, osmium, zirconium, and samarium among others.",10.1002/anie.200702056,2007-09-06,0.5954306902709684
Synthesis,Synthesis of 2-Alkenyl-Tethered Anilines,"Three general routes for the synthesis of (E)-2-alkenyl-tethered anilines have been developed. The first route involves a 3-aza-Cope rearrangement of N-allylic anilines in the presence of a Lewis acid. The requisite N-allylic anilines were prepared by the addition of vinylmagnesium reagents to the corresponding aldimines. The second route details a direct cross-metathesis of 2-allylic or 2-homoallylic anilines with styrenes. The third route involves a palladium-catalyzed C–N cross-coupling of aryl halides. Taken together, these three strategies allowed access to the requisite aniline substrates with pendant alkenes at the 2-position with excellent trans selectivities.",10.1055/s-0036-1589002,2017-05-04,0.5954258810659638
Tetrahedron,N-carbamoyl-4-diphenylphosphino-2-diphenylphosphinomethylpyrrolidines(CAPP). Efficient new chiral ligands for asymmetric hydrogenation,,10.1016/s0040-4039(00)78836-8,1980-01-01,0.5954211939370526
Tetrahedron,Highly efficient method for coriolin synthesis,,10.1016/s0040-4039(96)02328-3,1997-01-01,0.5954200159659595
Journal of Organic Chemistry,A Concise Synthesis of the Naphthalene Portion of Purpuromycin,"A concise synthesis of naphthalene compounds for incorporation into a synthetic sequence for the rubromycin family of natural products is presented. These highly substituted naphthalenes are generated in seven and nine steps, respectively, from 2,4,5-trimethoxybenzaldehyde. Three ring-forming methods were explored and the controlled oxygenation of different positions was investigated to yield differentially substituted/protected systems. Key steps to the final products include a Stobbe condensation to form the ring system and a novel series of regioselective oxidations to introduce the required oxygen functionality. These naphthalene products incorporate orthogonal protecting groups and are suitable for combination with a variety of coupling partners.",10.1021/jo7024114,2008-02-08,0.5954110598237207
Tetrahedron,"An efficient and practical synthesis of diphenyl cyanomethylenephosphonate: Applications to the stereoselective synthesis of cis-α,β-unsaturated nitriles",,10.1016/s0040-4039(97)10836-x,1998-03-01,0.5954017060113392
Journal of Organic Chemistry,Synthesis of γ-Monofluorinated Goniothalamin Analogues via Regio- and Stereoselective Ring-Opening Hydrofluorination of Epoxide,"A stereoselective synthesis of the biologically interesting γ-monofluorinated goniothalamin analogue 2a was described. The features of the synthesis included regioselective reduction of the unprotected hydroxypropynyl moiety of compound 10 by Red-Al, asymmetric Sharpless epoxidation of allyl alcohol 11, and regio- and stereoselective ring-opening hydrofluorination of the hydroxypropynyl epoxide 14 with Et(3)N·3HF in high ee and dr. The chiral hydroxypropynyl fluorohydrin 15 was used as a valuable building block for preparation of a range of γ-monofluorinated α,β-unsaturated δ-lactones.",10.1021/jo200611w,2011-07-08,0.5953994316148333
Tetrahedron,"A new efficient deprotection of azines, hydrazones and oximes. An excellent route for exchanging oxygen isotopes in carbonyls",,10.1016/j.tetlet.2005.11.090,2005-12-10,0.5953990065986685
Tetrahedron,Total synthesis of the novel angiogenesis inhibitors epoxyquinols A and B,,10.1016/s0040-4039(03)00621-x,2003-04-01,0.5953869319731082
Tetrahedron,"Total synthesis of 1-deoxy-7,8a-di-epi-castanospermine and formal synthesis of pumiliotoxin-251D",,10.1016/j.tetlet.2012.08.061,2012-08-24,0.5953844120102502
Journal of Organic Chemistry,"Ring Expansion of Isatins <i>via</i> 1,2-Phospha-Brook Rearrangement: A Route to the Synthesis of 2-Quinolinone-Derived <i>p</i>-Quinone Methides","A Lewis acid-mediated one-carbon homologation approach to installing a 2-quinolinone core embedded with para -quinone methides, in a high yield of up to 92%, and with high regioselectivity has been developed. Also, post-synthetic modifications, including C–P, C–S, and C–C bond formations, have been demonstrated by the 1,6-addition of suitable nucleophiles. Further, cyclopropanation of 2-quinolinone-embedded p -QM is also demonstrated affording a contiguous quaternary spiro center.",10.1021/acs.joc.2c01929,2022-12-02,0.5953808691269749
Angewandte Chemie International Edition,"Design, Synthesis, and Application of a Family of Chiral Non‐C <sub>2</sub> ‐Symmetric NHCs with a Fused Sidechain","Abstract Although a considerable number of chiral nitrogen heterocyclic carbenes (NHCs) have been developed yet it is highly necessary to develop new NHCs bearing multiple sites for facile modifications of both electronic nature and steric hindrance. Herein, we uncover a new family of chiral non‐C 2 ‐Symmetric NHCs with a fused sidechain, whose precursors are synthesized by a simple five‐step route. The synthesis includes Pd‐catalyzed cross‐coupling or nucleophilic addition/oxidation, chiral phosphoric acid‐catalyzed asymmetric reduction of 2‐aryl‐quinolines, bromination at C8, Buchwald–Hartwig amination, and cyclization with methyl orthoformate. Among nine prepared NHCs, YC‐NHC8 is the optimal ligand for Cu(I)‐catalyzed asymmetric S N 2′ silylation, YC‐NHC3 works as the best ligand for Cu(I)‐catalyzed enantioselective conjugate silylation of simple α,β‐unsaturated amides, and YC‐NHC9 serves as the most suitable ligand for copper(I)‐catalyzed asymmetric silylation of azadienes. Remarkably, these three reactions are successfully run under a catalyst loading of 0.1 mol%, indicating that YC‐NHCs may have the potential to be broadly used in efficient asymmetric transition metal catalysis.",10.1002/anie.202508572,2025-04-23,0.5953761148156621
Angewandte Chemie International Edition,Stereocontrolled Synthesis of Trichodermatide A,"Hard core made easy: The pentacyclic core of trichodermatide A was stereoselectively synthesized from a bis(1,3-cyclohexanedione) derivative by a ring-closing reaction followed by an intramolecular ketal formation (see scheme; PPTS=pyridinium p-toluenesulfonate). The first total synthesis of trichodermatide A was then completed by the introduction of three hydroxy groups.",10.1002/anie.201210099,2013-02-18,0.5953572234571882
European Journal of Organic Chemistry,Towards Immunoproteasome‐Specific Inhibitors: An Improved Synthesis of Dihydroeponemycin,"Abstract Eponemycin, an antitumor and antiangiogenic epoxy ketone natural product, is previously shown to target proteasome for its activity. Although there have been many synthetic approaches developed, practical and efficient synthetic strategy for eponemycin has yet to be accomplished. Here, we report an efficient new route for the preparation of dihydroeponemycin, an active eponemycin derivative. This will aid the design of proteasome inhibitors with novel activity. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2005)",10.1002/ejoc.200500437,2005-09-23,0.5953527475223579
Organic Process Research & Development,Scaleable Syntheses of Isomeric Limonene Aziridines from the Commercially Available Mixture of <i>cis</i>- and <i>trans</i>-Limonene Oxides,A short and efficient route to both isomers of limonene aziridine is described. The process is amenable to scale-up and allows easy access to multigram quantities of these highly useful chiral building blocks.,10.1021/op0498464,2005-02-11,0.5953493311556031
Synlett,Synthesis of the C13-C23 Segment of Tedanolide,The synthesis of the C13-C23 segment of tedanolide is described making use of orthogonal protecting groups in the construction of the carbon skeleton and for the selective liberation of hydroxyl groups in the endgame of the total synthesis.,10.1055/s-2005-862391,2005-01-01,0.5953492535703232
Tetrahedron,"Synthesis of a hexahydropyrimido[1,2-a]azepine-2-carboxamide derivative useful as an HIV integrase inhibitor",,10.1016/j.tetlet.2007.09.072,2007-09-17,0.5953476453622197
Tetrahedron,Asymmetric synthesis of (3R-)-and (3S-)-hydroxy-5-pentanolides,,10.1016/s0040-4039(01)91028-7,1984-01-01,0.5953462867801879
Angewandte Chemie International Edition,Facile Bucky‐Bowl Synthesis by Regiospecific Cove‐Region Closure by HF Elimination,Building bowls: An effective intramolecular aryl–aryl coupling is the key step in rational fullerene synthesis and in synthesis of extended buckybowl structures. Such a process can be embodied very efficiently through quantitative HF elimination on active Al2O3. The process is characterized by an unprecedentedly high chemoselectivity and regiospecificity.,10.1002/anie.201200516,2012-04-04,0.5953458679343829
Synthesis,"Efficient and Scalable Syntheses of 1,2-Thiaselenane-4-amine and 1,2-Thiaselenane-5-amine","Abstract The first regioselective syntheses of 1,2-thiaselenane-4-amine (TSA4) and 1,2-thiaselenane-5-amine (TSA5) are developed. Both are redox motifs with high value in chemical biology that until now were hindered by tedious synthesis. An aziridine intermediate and a kinetically controlled S-acylation were leveraged for regioselective chalcogen installations. Short, fast sequences were optimised with just one or two chromatographic steps that cheaply deliver these motifs on scale for high throughput inhibitor screening, and thus provide a robust methodology for assembling other selenenyl sulfides.",10.1055/a-2022-1398,2023-01-30,0.5953456676548312
Angewandte Chemie International Edition,"Total Synthesis of Pentabromo‐ and Pentachloropseudilin, and Synthetic Analogues—Allosteric Inhibitors of Myosin ATPase",Stopping myo: The total syntheses of the title compounds have been achieved using a highly efficient silver(I)-catalyzed cyclization of N-tosyl-homopropargylamines. The pseudilin derivatives represent a novel class of myosin inhibitors. A new allosteric binding pocket of the Dictyostelium myosin-2 motor domain has been identified for pentabromopseudilin (1) by using an X-ray crystal structure determination of the inhibitor–protein complex.,10.1002/anie.200903743,2009-09-08,0.5953445721228336
Synthesis,"Synthesis of the Pyranonaphthoquinones Dehydroherbarin, (+)-Astropaquinone B and (+)-Astropaquinone C en Route to Ascomycones A and B","The total syntheses of the pyranonaphthoquinone natural products dehydroherbarin, (+)-astropaquinone B and (+)-astropaquinone C are described. A late stage oxidation strategy employed for the synthesis of the astropaquinones was not amenable to the conversion of dehydroherbarin into the ascomycones. The syntheses of astropaquinones B and C reported herein constitute the first total syntheses and their absolute stereochemistry was determined to be (1R,3S). © Georg Thieme Verlag Stuttgart New York.",10.1055/s-0029-1218832,2010-06-18,0.5953436821086509
Tetrahedron,"Efficient, enantioselective synthesis of a β,β-disubstituted carboxylic acid by Ru-XylPhanePhos-catalyzed asymmetric hydrogenation",,10.1016/j.tetlet.2008.06.068,2008-06-21,0.5953422403346385
Organic Letters,Synthetic Studies toward Amphidinolide B<sub>1</sub>:  Synthesis of the C<sub>9</sub>−C<sub>26</sub> Fragment,"[reaction: see text] The synthesis of the C9-C26 portion of amphidinolide B1 is described. A Fleming allylation followed by elimination was employed for the construction of the C13-C15 diene portion. Sharpless asymmetric dihydroxylation was utilized for regioselective functionalization of a styrene-derived alkene, in the presence of the C13-C15 diene functionality. A highly diastereoselective aldol reaction was developed to establish the C18 stereochemistry.",10.1021/ol051544e,2005-08-19,0.5953390994906896
Angewandte Chemie International Edition,Divergent Total Syntheses of (+)‐Vulgarisins A–E,"The asymmetric total syntheses of (+)-vulgarisins A-E, which share a rare and highly oxygenated [5-6-4-5] tetracyclic core structure that were isolated from P. vulgaris Linn., have been described for the first time in a divergent manner. Key transformations include: 1) a catalytic asymmetric intramolecular cyclopropanation to forge the A ring bearing desired stereochemistry at C14; 2) a one-pot borylation/conjugate addition process for creation of the C1-C11 bond; 3) a Wolff ring contraction to assemble the bicyclo[3.2.0]heptane subunit (CD rings); and 4) a stereocontrolled pinacol cyclization for construction of the central B ring of the natural products.",10.1002/anie.202303668,2023-04-10,0.5953388102204556
Organic Letters,Enantioselective Organocatalytic Conjugate Addition in a Tandem Synthesis of δ-Substituted Cyclohexenones and Four-Step Total Synthesis of Penienone,"A bisperfluorotoluyl-BINOL catalyzed conjugate addition of trifluoroborate salts to doubly vinylogous esters and aldol condensation synthesized chiral δ-substituted cyclohexenones with high yields and enantioselectivities (10 examples, up to 89% yield, 89-98% ee). Stepwise and single-pot sequences were developed, with the former also providing β-substituted masked ketoaldehydes containing a vinyl ether. The transformation was used in a four-step total synthesis of penienone (24% overall yield), ≤ half the steps as in previous syntheses.",10.1021/acs.orglett.2c01976,2022-07-15,0.5953149646647625
Angewandte Chemie International Edition,A General Strategy for the Construction of Calyciphylline A‐Type Alkaloids: Divergent Total Syntheses of (−)‐Daphenylline and (−)‐Himalensine A,"Abstract An efficient general strategy for the synthesis of the Daphniphyllum alkaloids via the rapid construction of a common core intermediate has been established, based on which a divergent total synthesis of (−)‐daphenylline and (−)‐himalensine A has been accomplished in 16 and 19 steps, respectively. The present work features an enantioselective Mg(ClO 4 ) 2 ‐catalyzed intramolecular amidocyclization to construct the aza‐bridged core structure; a Cu‐catalyzed intramolecular cyclopropanation and subsequent phosphine‐catalyzed Cope‐type rearrangement to furnish the himalensine A scaffold; and a one‐pot Diels–Alder/aromatization method to assemble the aromatic skeleton of daphenylline.",10.1002/anie.202016212,2021-02-11,0.595314142709745
Organic Letters,A Concise Total Synthesis of (±)-Trigonoliimine B,"Trigonoliimine B, a hexacyclic alkaloid, is synthesized in seven steps from simple starting materials. The synthesis features the use of an α-isocyanoacetate as a glycine template for the preparation of an α,α-disubstituted α-amino ester that is appropriately functionalized for the construction of C, D, and E rings. Sulfolane was found to be the solvent of choice for the unprecedented Bischler-Napieralski reaction implemented for the construction of a seven-membered ring with concurrent formation of an exo-imine function.",10.1021/ol300249y,2012-02-22,0.5953059554413932
Synlett,Synthesis of Hydroxy-7<i>H</i>-benzo[<i>c</i>]fluoren-7-ones,"An efficient synthesis of 2-, 3- and 4-hydroxy-7H-benzo[c]fluoren-7-ones, useful intermediates for the synthesis of photochromic naphthopyrans, is described. The synthetic approach involves the use of oxazolines as activating groups for aromatic ­nucleophilic substitution and starts with readily available di­methoxynaphthaldehydes.",10.1055/s-2004-822890,2004-01-01,0.595297895571398
Organic Letters,Ruthenium-Catalyzed Alkyne−Propargyl Alcohol Addition. An Asymmetric Total Synthesis of (+)-α-Kainic Acid,"A novel route to the neuroexcitatory amino acid, kainic acid, is developed. The key concept derives from a ruthenium-catalyzed cycloisomerization of a tethered alkyne-propargyl alcohol to form a cyclic 2-vinyl-1-acyl compound. A single stereocenter introduced by an asymmetric reduction of a ketone sets the stage for all the other stereocenters. A novel 1,6-addition of silyl cuprate serves to install a hydroxyl group at the diene termines. [reaction: see text]",10.1021/ol034241y,2003-04-08,0.5952886537334492
Journal of the American Chemical Society,"Biocatalytic Synthesis of Pikromycin, Methymycin, Neomethymycin, Novamethymycin, and Ketomethymycin",A biocatalytic platform that employs the final two monomodular type I polyketide synthases of the pikromycin pathway in vitro followed by direct appendage of D-desosamine and final C-H oxidation(s) in vivo was developed and applied toward the synthesis of a suite of 12- and 14-membered ring macrolide natural products. This methodology delivered both compound classes in 13 steps (longest linear sequence) from commercially available (R)-Roche ester in >10% overall yields.,10.1021/ja404134f,2013-06-18,0.5952782522433512
Synthesis,"A Practical, Enantioselective Synthesis of the Fragrances Canthoxal and Silvial®, and Evaluation of Their Olfactory Activity",The fragrances ( S )-(+)- and ( R )-(–)-canthoxal [( S )-(+)- and ( R )-(–)-3-(4-methoxyphenyl)-2-methylpropanal] and (+)- and (–)-Silvial ® [(+)- and (–)-3-(4-isobutylphenyl)-2-methylpropanal] have been synthesized in high enantiopurity via a simple four-step strategy starting from the commercially available 4-substituted benzaldehydes. The key synthetic step is the catalytic asymmetric hydrogenation of the appropriate 3-aryl-2-methylacrylic acid which has been carried out employing an in situ prepared ruthenium/axially chiral phosphine catalyst (up to 98% ee). The olfactory activity of the single enantiomers has been evaluated.,10.1055/s-0034-1379254,2014-10-24,0.5952781627450877
Journal of Organic Chemistry,Stereochemical Definition and Chirospecific Synthesis of the Peptide Deformylase Inhibitor Sch 382583,"The recently reported natural product Sch 382583 (1), an inhibitor of peptide deformylase, has been synthesized in 16 steps from commercially available starting materials. The three chiral centers were set by a combination of chiral auxiliary and chiral pool approaches. The succinate 5 and piperazic acid 9 moieties were obtained by Evans oxazolidinone imide enolate alkylation and hydrazination/cyclization, respectively, and the aminohexanone side chain 13 was prepared via Grignard substitution of the Weinreb amide derived from l-valine. Spectroscopic data for the resulting synthetic material, compared with the data reported for the natural product, established that the previously unassigned valine ketone stereocenter (C-4) has the S-configuration.",10.1021/jo035667t,2004-01-31,0.5952759270456828
Journal of Organic Chemistry,"An Improved Procedure for the Synthesis of Benzimidazoles, Using Palladium-Catalyzed Aryl-Amination Chemistry","New, improved conditions have been developed and optimized for the synthesis of benzimidazoles by intramolecular palladium-catalyzed aryl-amination chemistry. This methodology, combined with a ""catch and release"" purification strategy, has led to a range of these heterocycles being prepared rapidly and in excellent yield.",10.1021/jo034824l,2003-07-31,0.5952716060593796
European Journal of Organic Chemistry,"Chemoenzymatic Synthesis of Stegobinone and Stegobiol, Components of the Natural Sex Pheromone of the Drugstore Beetle (<i>Stegobium paniceum L.</i>)","Abstract NADPH‐dependent ketoreductases were used for the chemoenzymatic stereoselective synthesis of the two componentsof the natural sex pheromone of the drugstore beetle. The key step in the asymmetric synthesis was the enzymatic reduction of an α‐methyl‐1,3‐diketone and an α‐methyl‐β‐keto ester, which finally led to the preparation of crystalline stegobinone and stegobiol.",10.1002/ejoc.201101319,2011-11-02,0.5952691132223296
Tetrahedron,"MgCl2 catalyzed one-pot synthesis of 2-hydroxy-3-((5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)(phenyl)methyl)naphthalene-1,4-dione derivatives in EG",,10.1016/j.tetlet.2016.01.089,2016-01-28,0.5952646816858659
European Journal of Organic Chemistry,"Diastereoselective Addition of Chiral (2-Lithiophenyl)acetaldehyde Acetals to Various Imines as Key Step in the Asymmetric Synthesis of 1-Aryltetrahydroisoquinolines, Part 4","A novel asymmetric synthesis of 1-aryl-1,2,3,4-tetrahydroisoquinolines has been developed. The key step in this synthesis is the diastereoselective addition of homochiral (2-lithiophenyl)acetaldehyde acetals to the sulfonylimine 25 and to the arylimines 28 and 31. The best diastereoselectivity is obtained by addition of the bis(2-methoxypropan-2-yl)-substituted 1,3-dioxolane 6e to benzylidene-p-anisidine (31) with an HPLC-determined diastereomeric ratio 32c/33c = 92.1:7.9. The N-tosyl and the N-(4-methoxyphenyl) groups of the addition products 26d, 27d, 32c, and 33c are cleaved with sodium in liquid ammonia and ammonium cerium(IV) nitrate, respectively, to yield the primary amines 35 and 36. The acid-catalysed cyclization of the sulfonamides 26d and 27d and the carbamates 37 and 38, prepared from 35 and 36, leads to the enantiomerically pure dihydroisoquinolines 40 and 41, respectively. During the cyclization of the sulfonamides 26d, 27d and the carbamates 37, 38 the chiral auxiliary – the diol 39 – is cleaved unchanged and can be recovered in good yields.",10.1002/(sici)1099-0690(199902)1999:2<503::aid-ejoc503>3.0.co;2-i,1999-02-01,0.5952615467093381
Angewandte Chemie International Edition,Formation of Enehydrazine Intermediates through Coupling of Phenylhydrazines with Vinyl Halides: Entry into the Fischer Indole Synthesis,"Cut to the chase: Direct formation of an enehydrazine, an intermediate in the classic Fischer indole synthesis, solves the regioselectivity problem associated with indolization. This approach not only achieves selective synthesis of indoles through proper selection of the vinyl halide, but also leads to quick construction of desoxyeseroline and esermethole, as well as the key structural motif in the Akuammiline alkaloid vincorine.",10.1002/anie.201207173,2012-12-06,0.5952603610797583
Angewandte Chemie International Edition,Total Synthesis and Structural Revision of (+)‐Uprolide G Acetate,"The first, asymmetric total synthesis of the proposed structure of (+)-uprolide G acetate (UGA) is reported, and the spectral properties of the synthetic compound clearly differed from those reported for natural UGA. On the basis of comprehensive analysis of the NMR data, two possible structures for the natural UGA were proposed and their total synthesis achieved, thus leading to the identification and confirmation of the correct structure and absolute configuration of the natural UGA. This synthesis was enabled by development of a novel synthetic strategy, which revolved around three key cyclization reactions: an Achmatowicz rearrangement, Sharpless asymmetric dihydroxylation/lactonization, and ring-closing metathesis. These synthetic studies pave the way for further studies on this class of structurally unusual cytotoxic cembranolides.",10.1002/anie.201409618,2014-11-10,0.5952595727051511
Tetrahedron,A facile route for the preparation of 4-aminomethylacridine and its derivatives,,10.1016/s0040-4039(01)96927-8,1971-01-01,0.5952576012292891
Journal of Organic Chemistry,General Stereodivergent Enantioselective Total Synthetic Approach toward Macrosphelides A–G and M,A straightforward enantioselective total synthesis algorithm for the preparation of 8 out of 13 macrosphelides within 9-11 steps starting from tert-butyl sorbate is presented. The use of a cyclic sulfate as both protecting and reactivity directing group is the key element within this algorithm. A high-pressure transesterification allows for the selective ring-enlargement of the 15-membered macrosphelides into the 16-membered counterparts. The absolute configurations of the natural products were unambiguously assigned both by the chemical synthesis and by X-ray structure analysis.,10.1021/acs.joc.5b01171,2015-07-23,0.5952488406499709
Organic Letters,Total Synthesis of Lysergic Acid,"A total synthesis of lysergic acid was accomplished. Key features of our synthesis include stereoselective construction of the stereogenic centers at the allylic positions by using the Evans aldol reaction, and a sequential process with a ring-closing metathesis and an intramolecular Heck reaction to construct the C and D rings.",10.1021/ol4019562,2013-08-06,0.5952381638902885
Tetrahedron,"Synthesis of benzofuro[3,2-b]indolines via regioselective electrooxidative coupling of indoles and phenols",,10.1016/j.tetlet.2020.152603,2020-11-04,0.5952374318325473
Tetrahedron,Regioselective synthesis of multifunctionalised porphyrins-coupling of mono-(pentafluorophenyl)porphyrins to electrophiles,,10.1016/s0040-4039(99)01615-9,1999-10-01,0.5952374318325473
Journal of Organic Chemistry,First Total Synthesis of Phenylpyridine Analogues of the Antimitotic Rhazinilam,"The first synthesis of phenylpyridine analogues of rhazinilam and evaluation of these new structures as inhibitors of microtubule disassembly by interaction with tubulin are described. The synthesis is based on such key steps as picolinic metalation, hetero-ring cross-coupling and reduction of an acetyl group to an ethyl group. Elaboration of a quaternary picolinic carbon is one of the challenges of the synthesis. Biological evaluation of compounds bearing a quaternary picolinic carbon showed interactions with tubulin similar to (-)-rhazinilam but at a lower level.",10.1021/jo0014156,2001-03-22,0.5952348574935235
Synlett,Stereoselective Synthesis of New β-Lactams from 2-(1H-Pyrrol-1-yl)-1-propen-1-one as a Novel Ketene,New trans -β-lactams have been stereoselectively prepared by the reaction of N -pyrrolylpropanoic acid with 2-chloro-1-methylpyridinium iodide and aromatic imines in the presence of triethylamine as a base via in situ generation of methyl-2-(1 H -pyrrol-1-yl)ketene as a novel heteroarylketene. The trans- β-lactam was formed either as a single isomer or as the major isomer.,10.1055/s-0033-1339520,2013-08-14,0.5952344313235781
Journal of Organic Chemistry,Synthesis of (−)-α-Kainic Acid via TMSCl-Promoted Pd-Catalyzed Zinc-ene Cyclization of an Allyl Acetate,"A highly practical synthesis of enantiopure (-)-α-kainic acid is accomplished in 37% overall yield, using 13 linear steps and a minimum of chromatographic separations via an unprecedented TMSCl-promoted palladium-catalyzed zinc-ene cyclization of an allyl acetate.",10.1021/jo201341q,2011-08-25,0.5952322939574533
Tetrahedron,An efficient and enantioselective synthesis of a chiral primary amine,,10.1016/s0040-4039(00)73087-5,1994-05-01,0.5952289333060671
Organic Process Research & Development,"Process Research and Development and Scale-up of a 4,4-Difluoro-3,3-dimethylproline Derivative","The multikilogram production of the proline derivative 1, a key intermediate of a HIV protease inhibitor, required the design of a synthetic route able to be safely, effectively, and easily scaled up. Synthesis of the proline skeleton began with construction of racemic glycine derivative 4, via an ester enolate Claisen rearrangement of Boc-glycine 3-methyl-but-2-enyl ester ( 3 ) in the absence of a Lewis acid. After a classical resolution of 4 with ( S )-phenylglycinol, ( S )- 4 was transformed into bromo-lactone 6b with NBS. The bromo-lactone was transformed to proline alcohol 8 via a base-promoted rearrangement involving lactone solvolysis. An NMR study suggested that a bicyclic lactone was initially formed, which subsequently opened by the methanol solvent to form 8 . The requisite ketone for fluorination was prepared via oxidation of the enantiomerically pure 8, using NaClO and catalytic TEMPO. gem -Difluoro proline 1 was then prepared from the ketone via fluorination with Deoxo-Fluor. During this study it was discovered that SiO 2 promoted fluorination by Deoxo-Fluor. This study allowed the production of 7.5 kg of 1 after 10 steps, in 4.5% molar yield and high purity (94–99% HPLC assay).",10.1021/op7001112,2008-02-21,0.595228813570344
Journal of Organic Chemistry,Diels−Alder Cycloaddition Approach to Puupehenone-Related Metabolites:  Synthesis of the Potent Angiogenesis Inhibitor 8-Epipuupehedione,"A new synthetic strategy toward puupehenone-related bioactive metabolites from sclareol oxide, based on a Diels-Alder cycloaddition approach, is described. Utilizing this, marine ent-chromazonarol and the potent angiogenesis inhibitor 8-epipuupehedione have been synthesized.",10.1021/jo0626663,2007-03-28,0.5952273458741296
Organic Letters,De Novo Asymmetric Synthesis of Daumone via a Palladium-Catalyzed Glycosylation,The enantioselective syntheses of daumone and two analogues have been achieved in seven to eight steps. This route relies upon a diasteroselective palladium-catalyzed glycosylation reaction for the formation of the anomeric bond. The asymmetry of the sugar and aglycone portion of daumone were introduced by Noyori reduction of an acylfuran and a propargyl ketone. A highly diastereoselective epoxidation and reductive ring opening established the desired C-2 and C-4 stereochemistry of daumone. [reaction: see text],10.1021/ol051383e,2005-08-06,0.5952178818418042
Green Chemistry,Synthesis of 3-arylamino-2-polyhydroxyalkyl-substituted indoles from unprotected saccharides and anilines,A simple and efficient one-pot synthetic protocol has been developed for the synthesis of structurally diverse indole derivatives by using unprotected sugars and aromatic amines.,10.1039/d3gc04440h,2024-01-01,0.5952163723889825
Synlett,Synthetic Studies Towards Phorboxazole B: Stereoselective Synthesis of the C3-C19 Bis-oxane Oxazole Fragment,A convergent and enantioselective synthesis of the C3-C19 bis-oxane oxazole fragment of phorboxazole B has been described. This work features highly efficient substrate-controlled reductions to construct the functionalised cis-oxane and a Mukaiyama aldol reaction followed by an intramolecular Williamson reaction leading to a trans-oxane.,10.1055/s-2003-41462,2003-01-01,0.5952160578538165
Journal of the American Chemical Society,A Short Enantioselective Total Synthesis of the Fundamental Pentacyclic Triterpene Lupeol,The first enantioselective synthesis of lupeol has been developed by applying two carefully crafted cation-pi cyclization stages to generate the pentacyclic structure with complete stereocontrol. The synthesis (Scheme 1) is noteworthy because of its brevity and also because it solves a longstanding problem in the field of natural product synthesis.,10.1021/ja906335u,2009-09-09,0.5952047061209845
European Journal of Organic Chemistry,First Total Synthesis of the Bioactive Arylnaphthyl Lignan 4‐<i>O</i>‐Glycosides Phyllanthusmin D and 4′′‐<i>O</i>‐Acetylmananthoside B,"Based on the application of phase‐transfer‐catalysis and Yu glycosylations, the first total syntheses of the arylnaphthyl glycosides phyllanthusmin D and 4′′‐ O ‐acetylmananthoside B, which have been claimed to be ideal antitumoral lead compounds in terms of cytotoxicity, cytotoxic selectivity, and a new mechanism of action, were achieved. Starting from easily accessible compounds, the two target molecules were obtained with longest linear sequences of 9 and 15 steps, in overall yields of 29 and 9 %, respectively. As part of this synthetic investigation, an efficient and scalable synthetic route to diphyllin was established, and the atropisomeric phenomenon in the arylnaphthyl glycosides was also confirmed.",10.1002/ejoc.201700556,2017-05-07,0.5951905706284859
Tetrahedron,Synthetic construction of a Lex determinant via gabriel amine synthesis and the glycopolymer involving highly clustered Lex residues,,10.1016/j.tetlet.2009.03.099,2009-03-20,0.5951894864253698
Journal of the American Chemical Society,"A Concise Total Synthesis of Dictyodendrins F, H, and I Using Aryl Ynol Ethers as Key Building Blocks","We report a concise total synthesis of dictyodendrin F and the first total syntheses of dictyodendrins H and I in six steps. In these syntheses, aryl ynol ethers were employed as the key building blocks to introduce aryl and heteroaryl rings in the dictyodendrins. This rapid synthesis utilized a novel hetero-[2 + 2]-cycloaddition reaction between two aryl ynol ethers to yield a cyclobutenone ring. The cyclobutenone was sequentially converted into a highly substituted carbazole via a retro-4π/6π-electrocyclization-N-acylation cascade reaction to provide the dictyodendrin core. Consecutive intramolecular oxidative coupling and deprotection gave dictyodendrins F, H, and I.",10.1021/jacs.6b06460,2016-07-29,0.5951885146448185
Tetrahedron,Action of elementary sulfur onto carbanions : a new route to dialkylpolysulfides,,10.1016/s0040-4039(00)92762-x,1980-01-01,0.5951845901532488
Journal of the American Chemical Society,Convergent Synthesis of a Fully Lipidated Glycosylphosphatidylinositol Anchor of <i>Plasmodium </i><i>f</i><i>alciparum</i>,"A highly convergent strategy for the synthesis of fully lipidated GPI anchors of malarial origin is reported. This strategy utilized three orthogonal protecting groups, which can be chemoselectively deprotected and functionalized in the late stage of the synthesis. Rapid access to the target GPIs in a highly efficient manner in sufficient quantities for the biological studies has been achieved.",10.1021/ja042374o,2005-03-17,0.5951789902479708
Tetrahedron,A New Radical Route to C4-Unsubstituted β-Lactams,,10.1016/s0040-4039(97)10476-2,1998-01-01,0.5951758984625037
Tetrahedron,Palladium(II)-mediated oxidative cyclization of N-carbamoyl aminoalkynes: a new route to γ-lactams,,10.1016/s0040-4039(99)01305-2,1999-09-01,0.5951671178178234
Tetrahedron,"Synthesis of (R)- and (S)-3-(tert-butyldimethylsilyloxy)-1-pyrroline N-oxides — chiral nitrones for synthesis of biologically active pyrrolidine derivative, Geissman-Waiss lactone",,10.1016/s0040-4039(98)00333-5,1998-04-01,0.5951646754423908
Tetrahedron,Improved synthesis of bioactive L-penicillamine via an economical and environment-friendly route,,10.1016/j.tetlet.2025.155573,2025-04-11,0.5951613402587955
Journal of the American Chemical Society,"Simple, Catalytic Enantioselective Syntheses of Estrone and Desogestrel","Highly enantioselective and very short syntheses of the bioactive forms of estrone (3) and desogestrel (4) are described using a chiral oxazaborolidinium catalyst (2) in the key initial step. Enantiomerically pure estrone was synthesized in eight steps from the readily available starting materials diene 5 and alpha,beta-enal 6 via intermediates 8 and 9. Desogestrel was synthesized using a similar strategy from diene 5 and alpha,beta-enal 11 via intermediates 12-17. The efficient syntheses of the chiral catalyst 2 and its enantiomer are also presented.",10.1021/ja048808x,2004-04-22,0.5951590786464993
Angewandte Chemie International Edition,Helicenes Built from Silacyclopentadienes via Ring‐by‐Ring Knitting of the Helical Framework,"Abstract Despite the apparent diversity of the protocols developed for the synthesis of helicenes, they essentially follow the same strategy: the closure of one, or several, internal rings in a key step. Herein, we report the synthesis of a new family of the heterohelicenes consisting of fused silacyclopentadiene rings formed via a facile and novel process. The treatment of oligo(alkynilydenesilylene) precursors of type H 2 C=CH−(SiMe 2 −C≡C) n −R ( n =3–7), bearing a vinyl group on the terminal silicon atom, with 9‐borabicyclononane leads first to 1,2‐hydroboration of the terminal double bond which then continues with a cascade of intramolecular 1,1‐carboboration reactions accompanied with the closure of a new silole ring after each step affording the target silahelicenes with, currently, up to seven condensed silole rings and with excellent yields. According XRD analysis, the seven fused silole rings of the heptacyclic compound 11 b form an almost complete turn of a helix. The presented one‐pot sequence of reactions is the first example of ring‐by‐ring knitting of a helical framework starting from easily available linear precursors.",10.1002/anie.201811140,2018-12-13,0.595157276684135
Angewandte Chemie International Edition,Divergent Total Syntheses of (−)‐Daphnezomines A and B and (+)‐Dapholdhamine B,"The daphnezomine A-type subfamily of Daphniphyllum alkaloids structurally features a unique aza-adamantane core skeleton and anticipates efficient strategies for completing their syntheses to thoroughly investigate their biological activities. Herein, divergent total syntheses of (-)-daphnezomines A and B and (+)-dapholdhamine B have been accomplished in 16-20 steps from a known epoxide via rapid construction of a common core intermediate. The present work features a Ti-mediated radical cyclization to establish the azabicyclo[3.3.1]nonane ring system, an intramolecular Heck reaction to install the bridgehead all-carbon quaternary stereocenter, a tandem deprotection/reduction/keto amine-carbinolamine tautomerization to furnish the aza-adamantane backbone, and an NIS-promoted 6-endo-trig aminocyclization to assemble the (+)-dapholdhamine B backbone.",10.1002/anie.202303402,2023-03-30,0.5951544925988184
Tetrahedron,The synthesis of α-stannyl-silanes and their use in the formation of alkenes,,10.1016/s0040-4039(00)92687-x,1991-07-01,0.5951491843624741
Tetrahedron,"Stereoselective opening of ring E in furostan sapogenins. An efficient route to 16,22R,26-hydroxy steroids",,10.1016/s0040-4039(01)92144-6,1974-01-01,0.595148702377188
Journal of Organic Chemistry,Straightforward Access to Enantioenriched 2-Allylpiperidine: Application to the Synthesis of Alkaloids,"An efficient stereocontrolled preparation of (2R,R(S))-2-allyl-(N-tert-butylsulfinyl)piperidine and its enantiomer is detailed. The sequence requires only two synthetic operations with one-column chromatography and is readily scaled up. The versatility of these chiral building blocks was exemplified by the total or formal synthesis of some natural and unnatural alkaloids.",10.1021/jo202211u,2011-11-27,0.5951416576588084
Synthesis,"Regiocontrolled Synthesis of 6,7-Dihydro-4H-pyrazolo[5,1-c][1,4]oxazines","Synthetic access to 6,7-dihydro-4H-pyrazolo[5,1-c][1,4]oxazines has been achieved in 3–4 steps from commercially available pyrazoles. Optimization of a protected hydroxyethyl group on N1 enabled the regiocontrolled construction of pyrazole-5-aldehydes in high yields; subsequent deprotection and reduction generated fused heterocyclic scaffolds bearing multiple substitution patterns. Moreover, the intermediate pyrazole lactols were shown to be versatile synthetic building blocks.",10.1055/s-0037-1610734,2019-10-08,0.5951355135735574
Synlett,Novel Catalytic Synthetic Route to Protected α-Methyl Threonine and the First Asymmetric Acetyl Migration in a Steglich Rearrangement Reaction,"A short synthetic route to protected a-methyl threonine 5 as a representative example for (protected) a-methylated a-amino-b-hydroxy acids bearing a stereogenic quaternary carbon center in a-position was developed. This multistep synthesis is based on the use of an easily accessible prochiral starting material in the presence of an organocatalyst, and allows the access to all four types of stereoisomers. In addition, the first enantioselective acetyl migration in a Steglich rearrangement reaction as a key step in this multistep synthesis of 5 was achieved. The heterocycle 12, which was used in Steglich rearrangement reaction for the first time, turned out to be an efficient organocatalyst leading to an enantioselectivity of up to 63% ee.",10.1055/s-2008-1032104,2008-02-26,0.5951354247624201
Tetrahedron,The design and synthesis of novel 3-[2-indol-1-yl-ethyl]-1H-indole derivatives as selective inhibitors of CDK4,,10.1016/j.tetlet.2005.01.054,2005-01-27,0.5951295089445922
Journal of Organic Chemistry,Synthesis of Deoxyaminosugar Cyclohexyl-<scp>l</scp>-callipeltose and Its Diastereomer Using Pd-Catalyzed Asymmetric Hydroalkoxylation,"Cyclohexyl- l -callipeltose, an aminodeoxysugar subunit of Callipeltoside A, was synthesized in six steps and 40% overall yield from readily available ( S )-4-methylpent-4-en-2-ol and cyclohexyloxyallene. The signature step is represented by Pd-catalyzed asymmetric intermolecular hydroalkoxylation that generates the key dihydropyran intermediate upon combination with the ring-closing metathesis reaction. Notably, an unnatural diastereomer of the target compound could also be obtained with comparable efficiency simply by using the enantiomeric ligand.",10.1021/acs.joc.9b01059,2019-06-12,0.59512396375893
Tetrahedron,A new route to cyclic amines by anionic cyclization,,10.1016/0040-4039(95)00200-v,1995-03-01,0.5951233752773081
Journal of Organic Chemistry,A Practical Synthesis of the F-Ring of Halichondrin B via Ozonolytic Desymmetrization of a<i> C</i><sub>2</sub>-Symmetric Dihydroxycyclohexene,C(2)-symmetric dihydroxycyclohexene 1 was desymmetrized via a one-pot Criegee ozonolysis/acylation protocol to afford acetal-lactone 2. Installation of the allyl side chain on the convex face of the bicyclic system and subsequent reduction provided the desired tetrahydrofuran 4 with the correct relative and absolute stereochemistries. Simple functional group manipulations led to the desired F-ring module 3 of halichondrin B.,10.1021/jo026302w,2002-12-31,0.5951225850505879
Tetrahedron,"A straightforward synthesis of the CERT inhibitor (1′R,3′S)-HPA-12",,10.1016/j.tetlet.2015.02.060,2015-02-20,0.5951194120356837
Journal of Organic Chemistry,"Gold-Catalyzed Cycloisomerization of Propargyl Pyruvates Enabling Unified Access to Tricladolides C and D, Chaetomellic Anhydride A, and Tyromycin A","Gold-catalyzed cycloisomerization of propargyl pyruvates has been developed as a key reaction to prepare maleic anhydride-type natural products. By combining with chemoselective epoxidation of the formed γ-alkylidenebutenolides and oxidative cleavage of epoxides, the first synthesis of tricladolide D and racemic tricladolide C has been achieved in 52 and 16% overall yields with five to seven steps starting from commercially available compounds. Further catalytic hydrogenation of alkenylated maleic anhydrides derived from γ-alkylidenebutenolides produced chaetomellic anhydride A (19% yield for six steps) and tyromycin A (15% yield for six steps), which provides flexible synthetic approaches to these naturally occurring dialkylated maleic anhydrides distinct from the documented ones.",10.1021/acs.joc.1c01890,2021-10-15,0.5951167451994049
Angewandte Chemie International Edition,The Total Synthesis of the Annonaceous Acetogenin 10‐Hydroxyasimicin,"Orthogonal and modular templating is an effective basis for the preparation of the biologically active annonaceous acetogenin 10-hydroxyasimicin (1). The versatile tartrate-derived 2,3-butanediacetal building block together with a highly diastereoselective hetero-Diels–Alder approach to the butenolide unit were usefully employed in this novel synthetic route.",10.1002/anie.200462264,2004-12-15,0.5951140619486529
Journal of Organic Chemistry,Total Synthesis of (−)-4-Hydroxyzinowol,"(-)-4-Hydroxyzinowol (1) is a potent inhibitor of P-glycoprotein, which has been implicated in multi-drug resistance in the treatment of cancer. The highly oxygenated structure of 1 comprises a trans-decalin (AB-ring) and a tetrahydrofuran (C-ring) and possesses six acyloxy, one hydroxy, and one alkoxy groups. The challenge of synthesizing 1 is particularly heightened by the nine consecutive stereogenic centers on the 10-carbon decalin skeleton. The total synthesis of this extremely complex structure was achieved in 36 steps from 5-acetoxynaphthalen-1-ol by the judicious application of powerful chemo- and stereoselective reactions. The rhodium-catalyzed asymmetric 1,4-addition of the isopropenyl group set the C7-stereocenter, and the remaining three cis-oriented hydroxy groups (C6, 8, and 9) of the B-ring were stereoselectively constructed in a stepwise fashion. The C5-tetra-substituted and C10-quaternary carbons at the juncture of the AB-ring were then introduced by oxidative dearomatization and Diels-Alder reaction, respectively. After acid-promoted formation of the C-ring ether, the C1-, 2-, 4- and 6-oxygen-based functional groups were stereoselectively installed to deliver the fully functionalized tricycle. Finally, the polyhydroxylated structure was converted to the polyacylated target molecule 1 via regioselective acetylation and benzoylation.",10.1021/jo501666x,2014-08-23,0.5951131538781131
Organic Letters,Copper-Mediated and Palladium-Catalyzed Cross-Coupling of Indoles and <i>N</i>-Methylpyridinium Salts: A Practical Way to Prepare 3-(Pyridin-2-yl)indoles,"Herein, a Pd/Cu bimetallic-catalyzed direct C–H heteroarylation of pyridines via the traceless protecting group strategy is described. A series of N -methyl-activated pyridines and 1-methylindoles are coupled with high regioselectivity to produce the corresponding 3-(pyridin-2-yl)indoles in moderate to good yields, wherein related electron-rich heterocycles (e.g., indole, 1-methylpyrrole, benzofuran, benzo[ b ]thiophene) are also applicable. Streamlined operation, good functional group tolerance, and late-stage modifications make this twofold C–H activation protocol an attractive route for the synthesis of 3-(pyridin-2-yl)indole derivatives.",10.1021/acs.orglett.3c01624,2023-07-13,0.595106571219656
Angewandte Chemie International Edition,Synthesis of Azepine Derivatives by Silver‐Catalyzed [5+2] Cycloaddition of <i>γ</i>‐Amino Ketones with Alkynes,Silver forges the ring: A new and practical silver-catalyzed [5+2] cycloaddition method has been developed for the synthesis of azepines through the formation of four new chemical bonds between a γ-amino ketone and an alkyne in one step. This method provides a new hetero-[5+2] cycloaddition strategy for the construction of seven-membered ring systems.,10.1002/anie.201304902,2013-08-27,0.5951058249984403
Organic Letters,Efficient Formal Synthesis of Oseltamivir Phosphate (Tamiflu) with Inexpensive <scp>d</scp>-Ribose as the Starting Material,"An efficient formal synthesis of oseltamivir phosphate (Tamiflu) has been achieved in 12 steps with use of the inexpensive and highly abundant D-ribose as the starting material. This concise alternative route does not utilize protecting groups and features the introduction of 3-pentylidene ketal as the latent 3-pentyl ether, the use of a highly efficient RCM reaction to form the Tamiflu skeleton, and selective functional group manipulations.",10.1021/ol9024716,2009-11-25,0.5951048339098539
Journal of Organic Chemistry,"Asymmetric Synthesis of Differentially Protected 2,7-Diaminosuberic Acid, a Ring-Closure Metathesis Approach","An efficient and versatile method has been developed for the synthesis of a selectively protected 2,7-diaminosuberic acid derivative. A Grubbs ring-closure olefin metathesis reaction was used as a key step on an allylglycine-derived template.",10.1021/jo971575q,1998-03-12,0.595102832749462
Angewandte Chemie International Edition,A Concise Total Synthesis of (±)‐Vibralactone,"Disclosed is a five-step synthesis of (±)-vibralactone, a biologically active terpenoid natural product. A key photochemical valence isomerization of 3-prenyl-pyran-2-one produces both the all-carbon quaternary stereocenter and the β-lactone at an early stage. Cyclopropanation of the resulting bicyclic β-lactone produces a strained housane structure that is converted to the natural product through a sequential ring expansion and reduction strategy. This concise and modular route to the natural product provides the shortest total synthesis of (±)-vibralactone reported to date.",10.1002/anie.201812711,2018-12-13,0.5951015863521626
Journal of Organic Chemistry,A Total Synthesis of (±)-3-<i>O</i>-Demethylmacronine through Rearrangement of a Precursor Embodying the Haemanthidine Alkaloid Framework,"A total synthesis of the racemic modification, (±)-2, of the tazettine-type alkaloid 3-O-demethylmacronine is described. The key steps are an intramolecular Alder-ene (IMAE) reaction and a lactam-to-lactone rearrangement of tetracycle 13, a compound that embodies the haemanthidine alkaloid framework.",10.1021/acs.joc.7b00340,2017-03-17,0.5950966251466971
Organic Letters,Enantioselective Total Synthesis of Natural Isoflavans: Asymmetric Transfer Hydrogenation/Deoxygenation of Isoflavanones with Dynamic Kinetic Resolution,A concise and highly enantioselective synthesis of structurally diverse isoflavans from a single chromone is described. The key transformation is a single-step conversion of racemic isoflavanones into virtually enantiopure isoflavans by domino asymmetric transfer hydrogenation/deoxygenation with dynamic kinetic resolution.,10.1021/acs.orglett.8b01034,2018-05-02,0.5950918719121455
Organic Process Research & Development,"Formation of (<i>S</i>)-5-Cyclohexyl-5-phenyl-1,3-dioxolane-2,4-dione: A Key Intermediate in the Synthesis of (<i>S</i>)-Oxybutynin Hydrochloride","The synthesis of the drug candidate ( S )-oxybutynin hydrochloride 1 is described. The procedure involves initial activation of ( S )-cyclohexylmandelic acid 2, using isobutylchloroformate, followed by reaction of the resulting intermediate with 4-(diethylamino)but-2-yn-1-ol, 3 . In this reaction, ( S )-5-cyclohexyl-5-phenyl-1,3-dioxolane-2,4-dione 7 was identified as a key transient intermediate leading to 1 . On the basis of the in situ IR spectroscopy data collected, the sequence of chemical events involved in the formation of intermediate 7, and its conversion to product and byproducts are described.",10.1021/op100021w,2010-06-16,0.5950733146454168
Tetrahedron,A diversity-oriented-synthesis protocol for scaffold discovery based on a general synthetic route to spirocycles,,10.1016/j.tetlet.2011.06.020,2011-06-25,0.5950636927520013
Organic Letters,Organocatalytic Enantioselective Total Synthesis of (−)-Arboricine,The tetracyclic indole alkaloid (-)-arboricine has been prepared using an asymmetric organocatalytic Pictet-Spengler reaction as the key step followed by a diastereoselective Pd-catalyzed iodoalkene/enolate cyclization. The absolute stereochemistry was unequivocally proven by X-ray crystallographic analysis and appeared to be opposite to the published structure in the original paper.,10.1021/ol900888e,2009-05-19,0.5950617350996282
Journal of Organic Chemistry,Enantioselective Approaches to Aminocyclopentitols:  A Total Synthesis of (+)-6-Epitrehazolin and a Formal Total Synthesis of (+)-Trehazolin,"Potent inhibitors of trehalase, such as trehazolin and its congeners, represent an attractive approach to the design of effective new insect control agents. In this report, enantioselective total syntheses of (−)-6-epitrehazolin and (+)-trehazolin were achieved using the asymmetric heterocycloaddition between [(benzyloxy)methyl]cyclopentadiene and the acylnitroso compound arising from in situ oxidation of (S) -mandelohydroxamic acid with tetrabutylammonium periodate. Further functionalization of the resulting 3,4,5-trisubstituted cyclopentene, either involving osmylation or epoxidation of the double bond, efficiently created pentasubstituted cyclopentanes. Introduction of the quaternary carbon in both synthesis targets was achieved via stereoselective osmylation of an intermediate 2,3,4,5-substituted 1-methylenecyclopentane.",10.1021/jo980050a,1998-04-22,0.595059404062323
Organic Letters,Efficient Asymmetric Synthesis of Radicicol Dimethyl Ether:  A Novel Application of Ring-Forming Olefin Metathesis,"A concise, stereospecific synthesis of radicicol dimethyl ether is presented. The strategy relies on a convergent three-stage assembly of the 14-membered lactone which has, as a key transformation, a novel ring-forming metathesis reaction utilizing a vinyl epoxide.",10.1021/ol0063252,2000-08-31,0.5950580601767628
Organic Letters,Reagent Controlled Direct Dehydrative Glycosylation with 2-Deoxy Sugars: Construction of the Saquayamycin Z Pentasaccharide,"The first synthesis of the pentasaccharide fragment of the angucycline antibiotic saquayamycin Z is described. By using our sulfonyl chloride mediated reagent controlled dehydrative glycosylation, we are able to assemble the glycosidic linkages with high levels of anomeric selectivity. The total synthesis was completed in 25 total steps, and in 2.5% overall yield with a longest linear sequence of 15 steps.",10.1021/acs.orglett.9b02056,2019-07-15,0.5950580026861102
Synlett,Practical Synthesis of Penems and Carbapenems Key Intermediate,"All articles of this category Titanium enolate-mediated aldol reaction of chiral N -phthaloyl-β-alanyl-1,3-benzoxazinone 5 with acetaldehyde furnished the (2 S , 3 R )- syn -aldol 6 in high yield with high stereoselectivity. Silylation of the hydroxy group of 6 followed by removal of the protective groups and cyclization gave the optically pure β-lactam 9 which was transformed into the acetoxyazetidinone 3 , a key intermediate of penems and carbapenems. acetoxyazetidinone - carbapenem - asymmetric aldol reaction",10.1055/s-1996-5463,1996-05-01,0.5950577114655122
Organic Process Research & Development,"Toward a Scalable Synthesis and Process for EMA401, Part II: Development and Scale-Up of a Pyridine- and Piperidine-Free Knoevenagel–Doebner Condensation","During route scouting for EMA401 ( 1 ), an angiotensin II type 2 antagonist, we identified the synthesis of key amino acid intermediate 2 via its cinnamic acid derivative 3 as a streamlined option. In general, cinnamic acids can be synthesized from the corresponding aldehydes by a Knoevenagel–Doebner condensation in pyridine with piperidine as an organocatalyst. We aimed to replace both of these reagents and found novel conditions involving toluene as the solvent and morpholine as the organocatalyst. Scale-up of the process allowed the production of 25 kg of cinnamic acid 3 that was of the quality required for process development of the subsequent phenylalanine ammonia lyase-catalyzed step. The modified conditions were found to be widely applicable to alternative aldehydes and thus are of relevance to practitioners of chemical scale-up.",10.1021/acs.oprd.0c00216,2020-08-20,0.5950551788059313
Journal of Organic Chemistry,New Strategy for the Synthesis of Iminoglycitols from Amino Acids,"A novel strategy for the enantioselective synthesis of polyhydroxypiperidines, which can be considered as iminoglycitols or 2,6-dideoxyazasugars, was developed. alpha-Benzolsulfonylamino esters served as a C(2)N building block while 2-bromo-3-(bromomethyl)oxazoles and -thiazoles contributed a C3-unit to the final piperidine ring. At first a dihydropyridine ring was established via alkylation and bromine-lithium exchange. The keto group of the resulting 5,6-dihydro[1,3]oxazolo- and 5,6-dihydro[1,3]thiazolo[4,5-c]pyridin-7(4H)-ones was reduced and, after alkylation reactions, the azole ring was cleaved, thus providing heteroatom substituents for the target piperdines. Protected 5-amino-3,4-dihydroxy and 5-amino-3-hydroxy-4-thiohydroxypiperdines were obtained in the talose series while Mitsunobu reaction of the intermiediates provided access to the altrose series.",10.1021/jo010665z,2002-04-17,0.595050587989743
Tetrahedron,"A two-step synthesis of aminopropylpiperidines via aminopropargylpyridines, suitable for the synthesis of a new class of 5-HT4 ligands",,10.1016/j.tetlet.2004.07.118,2004-08-27,0.5950498075730346
Organic Process Research & Development,Practical Synthesis of Tenofovir Alafenamide Fumarate Inspired by New Retrosynthetic Disconnection Featuring a Novel Carbon–Phosphorus Bond Construction Methodology,"Tenofovir alafenamide fumarate (TAF) is rising as a mainstay antiretroviral agent for the treatment of HIV and chronic HBV infections. A de novo practical synthesis of TAF circumventing tenofovir (PMPA) has been accomplished on a 7 g scale. This reimagined synthesis of TAF, inspired by a hitherto uncharted retrosynthetic disconnection, centers on the P -alkylation of silylated diphenyl phosphonate 11 (as acceptor) with methylthiomethyl (MTM) ether derivative 12 (as donor) in the presence of NIS/TfOH combination as a promoter to construct the strategic carbon–phosphorus bond. This PMPA-free synthesis of TAF not only removes the intrinsic drawbacks encountered by the PMPA-dependent commercial process but also is beneficial to the diversification of the synthetic portfolio of TAF. Furthermore, this type of P -alkylation reaction with defined stereochemistry could be deployed for the late-stage modification of druglike molecules and natural products to access valuable phosphonate derivatives.",10.1021/acs.oprd.3c00070,2023-05-19,0.5950445331377889
Tetrahedron,Studies toward the total synthesis of antibiotic roseophilin: A novel synthesis of the macrotricyclic part,,10.1016/s0040-4039(98)01450-6,1998-09-01,0.5950414032912825
Tetrahedron,An efficient chemoenzymatic route to dihydroxyacetone phosphate from glycidol for the in situ aldolase-mediated synthesis of monosaccharides,,10.1016/j.tetlet.2006.03.036,2006-03-24,0.5950333172585136
Synlett,Efficient Syntheses of the Polyene Fragments Present in Amphidinols,The C53-C67 and C53-C65 polyene fragments of amphidinols have been synthesized in an efficient and convergent fashion from sorbic acid in good overall yields (30-31%) by employing a chemoselective cross-metathesis of a Weinreb amide and a Julia-Kocienski olefination as the key steps.,10.1055/s-2007-984910,2007-07-20,0.5950253571267685
Synlett,Synthesis of Segment C of Tautomycin,"All articles of this category Synthesis of Segment C of tautomycin was accomplished from 2 D -sugar derivatives. New heteroconjugate addition strategy allowed stereocontrolled syntheses of the 2 sub-segments, C-1 and C-2, and 3 other diastereoisomers of the latter. Sub-segments were coupled between sulfone carbanion and epoxide electrophile to furnish the spiro ring moiety of the target compound. tautomycin - segment C - heteroconjugate addition - pseudoenantiomer - enantiomer - sulfone",10.1055/s-1995-4937,1995-03-01,0.5950195865212882
Tetrahedron,"A new synthesis of 1,1-diphenyl-3-arylisoquinolin-4-ones by the novel cyclization of 2-azabuta-1,3-dienes.",,10.1016/s0040-4039(00)98906-8,1985-01-01,0.5950139975660994
Synthesis,Synthesis of 4-Substituted 7-Azaindole Derivatives via Pd-Catalyzed C-N and C-O Coupling,The efficient substitution of 4-chloro-7-azaindoles by anilines and phenols via palladium-catalyzed C-N and C-O coupling is reported.,10.1055/s-2006-926310,2006-01-01,0.595009636257438
Synthesis,A Practical Synthesis of Cefcapene Pivoxil,All articles of this category (opens in new window),10.1055/s-0031-1289654,2011-12-22,0.595006591382184
Tetrahedron,Regioselective C2-lithiation of N-Boc-3-bromopyrroles: a novel approach towards the synthesis and scale-up of 3-(2-formyl-4-methyl-1-H-pyrrol-3-yl)propanoic acid,,10.1016/j.tetlet.2015.03.035,2015-04-11,0.5950036344345666
Tetrahedron,"Imidazolines in synthesis, I: lithio imidazolines-formation and -alkylation",,10.1016/0040-4039(81)80071-8,1981-01-01,0.5949989708995257
Tetrahedron,Dibutylamine-catalysed efficient one-pot synthesis of biologically potent pyrans,,10.1016/j.tetlet.2014.12.079,2014-12-19,0.5949972526919886
Green Chemistry,Organocatalytic synthesis of polysubstituted tetrahydrofurans from alkenes,"A novel, organocatalytic and environmentally friendly protocol for the synthesis of polysubstituted tetrahydrofurans from trivial starting materials has been described.",10.1039/c6gc02580c,2016-10-26,0.5949969236873952
Organic Process Research & Development,A New and Efficient Approach to Prepare <i>N</i>-Acetyl GM<sub>3</sub> Ganglioside via Trisaccharide [1→4] Lactone,"The N -acetyl GM 3 ganglioside (NAcGM 3 ) is an important glycosphingolipid currently used to prepare a new therapeutic cancer vaccine. Some quantities of this ganglioside were obtained by using [1→4] lactone as the trisaccharide protective function. Thus, sialylation of hexabenzyllactose acceptor with 5-acetyl neuraminylthiophenyl donor afforded the (2→3) trisaccharide as an α/β (3:1) mixture. The α-anomer was isolated through selective [1→4] lactone formation followed by chromatography. The lactone was hydrogenolyzed, per- O -acetylated, and selectively deacetylated, and a trichloroacetimidate donor was synthesized from the obtained compound. Azidosphingosine glycosylation, followed by azide group reduction and acylation of the resulting amino glycoside with stearic acid provided the protected ganglioside, which was finally subjected to the Zemplen’s procedure, before saponification, to obtain the NAcGM 3 in an overall yield of 11.5% at multigram scale.",10.1021/op300265r,2012-12-21,0.5949946923033727
Tetrahedron,Synthesis of (±)-palasonin,(±)-Palasonin (1) was prepared in nine steps from α-methoxycarbonylmaleic anhydride (3).,10.1016/0040-4039(96)00087-1,1996-02-01,0.5949855531146284
Journal of Organic Chemistry,"Synthesis of Elenic Acid, an Inhibitor of Topoisomerase II","A short, efficient synthesis of elenic acid, a marine natural product with interesting biological activity, has been completed. Critical features of the synthesis are the development of methodology for the one-pot elaboration of an alkyne to an ( E )-β,γ-unsaturated ester with a stereocenter at the α-position and the use of the zipper reaction of a 1-arylalkyne. This reaction has not been previously reported with aromatic substrates. The synthesis strategy provides considerable flexibility for the preparation of structural analogues.",10.1021/jo982260t,1999-03-05,0.5949849828735911
Organic Process Research & Development,"Improved Process for Preparation of Gemfibrozil, an Antihypolipidemic","An improved process for the preparation of gemfibrozil, an antihypolipodimic drug substance, with an overall yield of 80% and ∼99.9% purity (including three chemical reactions) is reported. Formation and control of possible impurities are also described. Finally, gemfibrozil is isolated from water without any additional solvent purification.",10.1021/op400034f,2013-06-18,0.5949794053164071
Tetrahedron,New approach in the synthesis of M6G,,10.1016/j.tetlet.2011.07.011,2011-07-10,0.5949576305195133
Tetrahedron,A new approach toward the synthesis of heterolignans,,10.1016/s0040-4039(02)01011-0,2002-07-01,0.5949576305195133
Tetrahedron,A new approach to the synthesis of linearly fused triquinanes,,10.1016/0040-4039(95)00826-x,1995-06-01,0.5949576305195133
Tetrahedron,"New approach to the synthesis of cyazofamid, fungicide",,10.1016/j.tetlet.2025.155747,2025-08-01,0.5949576305195133
Tetrahedron,"A new approach to the [6]paracyclophane system: synthesis of 2,3-dicarbethoxy[6]paracyclophane",,10.1016/s0040-4039(00)86777-5,1982-01-01,0.5949576305195133
Tetrahedron,A new approach to the synthesis of antitumoralkaloids with the lycorane skeleton,,10.1016/s0040-4039(00)74224-9,1992-04-01,0.5949576305195133
Tetrahedron,A new approach to the synthesis of hydrindanonecarboxylates,,10.1016/s0040-4039(01)87377-9,1973-01-01,0.5949576305195133
Tetrahedron,A new approach to the synthesis of 2β- and 3β-hydroxygibberellins,,10.1016/s0040-4039(00)96951-x,1987-01-01,0.5949576305195133
Tetrahedron,A new approach to the formal synthesis of (±)-α-cedrene,,10.1016/s0040-4039(00)60492-6,1993-04-01,0.5949576305195133
Tetrahedron,"New benzyne approach to the synthesis of dehydroaporphines, 4,5-dioxoaporphines and aristolactams",,10.1016/s0040-4039(00)86859-8,1982-01-01,0.5949576305195133
Tetrahedron,"A new approach to the synthesis of α-alkylidene-γ-butyrolactones and Δα,β-butenolides",,10.1016/0040-4039(76)80142-6,1976-12-01,0.5949576305195133
Synthesis,Synthesis of Benzo[<i>k</i>]phenanthridines: Another New Approach,,10.1055/s-1981-29612,1981-01-01,0.5949576305195133
Tetrahedron,SNAr macrocyclisation: A new approach towards the synthesis of D-O-E- segment of vancomycin,,10.1016/s0040-4039(97)01749-8,1997-10-01,0.5949576305195133
Tetrahedron,A new approach to the synthesis of symmetrical biflavones,,10.1016/s0040-4039(01)97549-5,1971-01-01,0.5949576305195133
Tetrahedron,A new approach to α-methylene-γ-butyrolactones. Synthesis of (−)-frullanolide.,,10.1016/s0040-4039(01)84854-1,1972-01-01,0.5949576305195133
Tetrahedron,A new approach to the synthesis of cyanogenic glycosides,,10.1016/s0040-4039(01)84203-9,1966-01-01,0.5949576305195133
Synlett,Studies Towards the Synthesis of Crotogoudin,"An effective synthesis of the tricyclic core structure of the new diterpene crotogoudin was achieved. The synthesis features an intermolecular domino Michael reaction to construct a bicyclo[2.2.2]octane motif and an aldol condensation to close ring B. Stork reductive alkylation with allyl bromide proceeded from the β side, resulting in the wrong stereochemistry at C-10.",10.1055/s-0032-1318366,2013-03-05,0.594955253336533
Tetrahedron,Synthetic Studies on Prostanoids. III. Stereochemistry of the Key Intermediate (IV) in the Total Synthesis of Prostaglandin F1α,,10.1016/s0040-4039(01)94037-7,1972-01-01,0.594949161957444
Organic Letters,Concise Synthesis of Chafurosides A and B,"The regioselective synthesis of chafurosides A (1) and B (2) from the same methyl ketone 5 was accomplished using a novel protecting group strategy. Both flavone rings were constructed from beta-diketone intermediate 4, which was readily obtained by condensation of an acyl donor and ketone 5. Construction of the dihydrofuran ring was achieved via an intramolecular Mitsunobu reaction.",10.1021/ol900689m,2009-04-27,0.594933550315408
Synthesis,"New Efficient Synthesis of Pyrido[2,3-<i>c</i>]coumarin Derivatives by Palladium-Catalyzed Heck Cyclization","Tetrahydropyrido[2,3-c]coumarin derivatives were synthesized by intramolecular radical cyclization and Heck coupling. This method allowed the synthesis of the backbone of the Santi­agonamine alkaloid.",10.1055/s-2007-990846,2007-11-26,0.5949313273499535
Organic Letters,"Total Synthesis of (±)-Lycorine from the <i>Endo</i>-Cycloadduct of 3,5-Dibromo-2-pyrone and (<i>E</i>)-β-Borylstyrene","A new synthetic route to (±)-lycorine, starting from the endo-cycloadduct of 3,5-dibromo-2-pyrone and (E)-β-borylstyrene, is reported. Boronate oxidation and a set of reactions including face-selective epoxidation provided the pivotal C1-OH group and C3/C3a double bond.",10.1021/ol502792p,2014-10-17,0.5949292761592224
Organic Letters,Total Synthesis of (+)-Cyanthiwigin AC,A 13-step synthesis of (+)-cyanthiwigin-AC (2) from (+)-Hajos-Parrish ketone derivative 8b and dimesylate 9c employing deconjugative spiro-bis-alkylation strategy is described. [reaction: see text].,10.1021/ol062304h,2006-10-24,0.5949266573768605
Angewandte Chemie International Edition,"Total Synthesis of the Protected Aglycon of Fidaxomicin (Tiacumicin B, Lipiarmycin A3)","Fidaxomicin, also known as tiacumicin B or lipiarmycin A3, is a novel macrocyclic antibiotic that is used in hospitals for the treatment of Clostridium difficile infections. This natural product has also been shown to have excellent bactericidal activity against multidrug-resistant Mycobacterium tuberculosis. In spite of its attractive biological activity, no total synthesis has been reported to date. The enantioselective synthesis of the central 18-membered macrolactone is reported herein. The key reactions include ring-closing metathesis between a terminal olefin and a dienoate moiety for macrocyclization, a vinylogous Mukaiyama aldol reaction, and a Stille coupling reaction of sterically demanding substrates. The retrosynthesis involves three medium-sized fragments, thus leading to a flexible yet convergent synthetic route.",10.1002/anie.201409464,2014-11-27,0.5949211432795907
Angewandte Chemie International Edition,Enantioselective Biomimetic Total Syntheses of Kuwanons I and J and Brosimones A and B,"The first enantioselective total syntheses of prenylflavonoid Diels-Alder natural products (-)-kuwanon I, (+)-kuwanon J, (-)-brosimone A, and (-)-brosimone B have been accomplished from a common intermediate based on a concise synthetic strategy. Key elements of the synthesis include a biosynthesis-inspired asymmetric Diels-Alder cycloaddition mediated by a chiral ligand/boron Lewis acid, as well as a process involving regioselective Schenck ene reaction, reduction, and dehydration to realize a biomimetic dehydrogenation for generation of the required diene precursor. Furthermore, a remarkable tandem inter-/intramolecular asymmetric Diels-Alder cycloaddition process was applied for the synthesis of (-)-brosimone A.",10.1002/anie.201404499,2014-07-07,0.5949202461210452
Journal of the American Chemical Society,Stereoselective Synthesis of Pamamycin-607,"A macrodiolide antibiotic pamamycin-607 was synthesized by joining two hydroxy acid components. Three cis-2, 5-disubstituted tetrahydrofuran rings in the molecule were stereoselectively prepared by radical cyclization reactions of beta-alkoxyvinyl ketone intermediates and a beta-alkoxymethacrylate substrate. The key step of the synthesis is characterized by the predominant threo product formation in the radical cyclization reaction of a beta-alkoxymethacrylate intermediate.",10.1021/ja0279646,2002-11-16,0.5949124912802782
Journal of the American Chemical Society,Enantioselective Total Synthesis of (+)-KB343,"A concise total synthesis of the complex guanidinium toxin KB343 is reported traversing through an unusual sequence of chemoselective transformations and strategic skeletal reorganization. The absolute configuration is confirmed through an enantioselective route, and the structures of all key intermediates and the natural product itself are unassailably confirmed through X-ray crystallographic analysis.",10.1021/jacs.3c01991,2023-03-30,0.5949100846900576
Tetrahedron,A facile tandem radical cyclization route to propellanes and its application to a total synthesis of modhephene,,10.1016/j.tetlet.2005.01.017,2005-01-25,0.5949096086726566
Journal of the American Chemical Society,Ten-Step Asymmetric Total Synthesis of (+)-Pepluanol A,") is presented. The synthesis route is very concise (10 steps) and features a Curtin-Hammett-driven stereoconvergent intramolecular Diels-Alder reaction. A Nozaki-Hiyama-Kishi reaction comprises the connective step, bringing together the seven-membered enone system bearing the dienophile and the diene in the side chain. Subsequent stereoconvergent IMDA reaction furnishes the carboskeleton of the natural product in only 7 steps. The reactions were carried out on a gram scale up to an advanced intermediate and including the stereoconvergent intramolecular Diels-Alder reaction.",10.1021/jacs.1c05257,2021-07-29,0.5949047354260464
Organic Letters,Synthesis of<i>e</i><i>nt</i>-Thallusin,"[reaction: see text] A three-step route from sclareol oxide (6) to bromo ester 4 in 53% overall yield was achieved using the efficient oxidation of an allylic bromide to an enal with bis(2,4,6-trimethylpyridine)silver(I) hexafluorophosphate in DMSO. Stille coupling of bromo ester 4 with stannylpyridine 5 gave the trimethyl ester of ent-thallusin in 54-92% yield by the stoichiometric conversion of 4 to a vinyl palladium intermediate prior to the addition of 5 to the reaction.",10.1021/ol0605777,2006-04-15,0.5949046614565929
Organic Letters,"Total Synthesis of Sialyl Inositol Phosphosphingolipids CJP-2, CJP-3, and CJP-4 Isolated from Feather Star <i>Comanthus japonica</i>","The first total synthesis of three echinodermatous sialyl inositol phosphosphingolipids, which exhibit unusual neuritogenic activity in the absence of nerve growth factor, are reported. Highlights of the syntheses include 9- O-methylation on sialic acid, inter-residual amide bond formation between sialic acid residues, and highly stereo- and regioselective sialylation of inositol. A key phosphodiester linkage between the mono-, di-, and trisialyl inositols and ceramide was formed at a late state employing the phosphoramidite method.",10.1021/acs.orglett.9b01229,2019-05-22,0.5949027789783772
Tetrahedron,Diastereoselective approach to novel octahydroisoquinolones and an extension to its one-pot synthesis,,10.1016/j.tetlet.2010.06.038,2010-06-12,0.5948986828253795
Tetrahedron,Preparation of 3-alkylpyridines. Formal total synthesis of Haliclamines A and B,,10.1016/s0040-4039(99)02120-6,2000-01-01,0.5948881866736034
Synthesis,Catalytic Enantioselective Total Synthesis of (–)-Pyridovericin,The first enantioselective catalytic total synthesis of (–)-pyridovericin is reported. The key steps involve a modified HWE reaction under aqueous conditions and an asymmetric iridium-catalyzed hydrogenation. This resulted in a highly modular and stereoselective approach that delivered the target natural product in high yield and stereoselectivity.,10.1055/s-0033-1340868,2014-02-27,0.5948858911350929
Synthesis,A Concise Stereoselective Total Synthesis of Herbarumin III,"A stereoselective total synthesis of the phytotoxic compound herbarumin III has been achieved by utilizing Crimmins’s aldol­ approach, 1,3-syn asymmetric reduction, and an olefin meta­thesis reaction as the key steps.",10.1055/s-2008-1067089,2008-05-16,0.5948809365874201
Tetrahedron,Selective hydroxyl protection of (+)-noviose via improved synthesis,,10.1016/j.tetlet.2009.02.194,2009-03-02,0.5948808716263257
Journal of Organic Chemistry,Total Synthesis of Aculeatin A via Double Intramolecular Oxa-Michael Addition of Secondary/Tertiary Alcohols,"A new synthetic strategy was developed for a concise total synthesis of aculeatin A as a single spiroisomer in both racemic and enantioselective fashions in 8-10 steps with ∼10% overall yield from the known alkyne 11, featuring phenol oxidative dearomatization, double intramolecular oxa-Michael addition of secondary/tertiary alcohols, and chemo- and stereoselective reduction of ketone. The new synthetic strategy greatly expedites the access to the potent antiprotozoal aculeatin A, 6-epi-aculeatin D, and their analogues.",10.1021/jo4026868,2014-01-06,0.5948761864064537
Tetrahedron,Squaramide catalyzed α-chiral amine synthesis,,10.1016/j.tetlet.2018.08.034,2018-08-21,0.5948719831610908
Journal of Organic Chemistry,Divergent Total Synthesis of Chaetoglines C to F,"The first total syntheses of chaetoglines C-F via a bioinspired and divergent synthetic strategy are reported. Chaetolines C and D were obtained from the condensation of hemiacetal and tryptophan methyl ester building blocks followed by functional group transformations. The synthesis of chaetogline E employed the diastereoselective Pictet-Spengler reaction, and the tetrahydro-carboline skeleton was further utilized as a precursor for an oxidative aromatization reaction to introduce the β-carboline moiety of chaetogline F.",10.1021/acs.joc.9b01076,2019-06-11,0.5948685573444741
Synlett,Research on the Synthetic Methodology for Lurasidone Hydrochloride,"Abstract In this study, the antipsychotic drug ruprasidone hydrochloride was synthesized using (1R,2R)-1,2-cyclohexanedimethanol as the starting material. The synthesis process was carried out through four steps: sulfonylation, N-alkylation, substitution, and acidification with hydrochloric acid. Eventually, lurasidone hydrochloride was obtained with a total yield of 34.3%, calculated based on (1R,2R)-1,2-cyclohexanedimethanol. The structure of the target compound was confirmed by 1H NMR and 13C NMR spectroscopic analyses. The reported synthetic process offers several advantages of high yield, simple steps, high cost-effectiveness and safe operation, and the synthetic process is suitable for industrial production. This study provides a methodological reference for the industrial manufacturing of ruprasidone hydrochloride.",10.1055/a-2705-9526,2025-09-19,0.5948648766187479
Tetrahedron,"Synthesis and Ag+-catalyzed cyclization of 2,3-dienamides",,10.1016/s0040-4039(02)00017-5,2002-02-01,0.5948610102899549
Tetrahedron,Borontrifluoride catalyzed cyclization of costunolide. Synthesis of 4α-hydroxycyclocostunolide,,10.1016/s0040-4039(01)96724-3,1971-01-01,0.5948610102899549
Tetrahedron,Novel ring transformation of quinolines to indole derivatives in two steps,,10.1016/s0040-4039(02)01059-6,2002-07-01,0.5948591834127612
Organic Letters,"Novel <i>C</i><sub>3</sub><i><sub>V</sub></i> -Symmetric Tripodal Scaffold, Triethyl <i>cis,cis,cis-</i>2,5,8- Tribenzyltrindane-2,5,8-tricarboxylate, for the Construction of Artificial Receptors","[reaction: see text] A novel C3V-symmetric scaffold, trindane 7, has been efficiently synthesized from 1,3,5-tris(bromomethyl)-2,4,6-tris(chloromethyl)benzene (1) in six steps with 47% overall yield. The control of all-syn stereochemistry in the tribenzylation step has been achieved by blocking one side of the trindane ring as metal carbonyl complexes. The potential utility of trindane 7 as a receptor skeleton has been examined with a urea derivative 12 toward several anionic guests.",10.1021/ol017294t,2002-02-13,0.5948557037385127
Synthesis,Recent Advances in Electrochemical Cascade Cyclization Reactions,"Abstract This review highlights recent progress in electrochemical cascade cyclization reactions for the synthesis of carbon rings and heterocycles, such as pyridines, quinolines, phenanthridines, cinnolines, 1,4-dihydroquinolines, oxindoles, imidazo[1,5-α]pyridines, imidazoles, etc. The works included herein are introduced in two major sections of heterocycle construction and carbocycle construction reactions, covering the works reported from 2012 to 2022. 1 Introduction 2 Electrochemical Cascade Cyclization for the Synthesis of Heterocycles 2.1 Synthesis of Pyridines, Quinolines, Phenanthridines, and Cinnolines 2.2 Synthesis of 1,4-Dihydroquinolines, Hexacyclic Sulfonamides, and Thiazines 2.3 Synthesis of Hydroisoquinolinones and Hydroquinolinones 2.4 Synthesis of Quinazolin-4(3H)-ones 2.5 Synthesis of 4H-3,1-Benzoxazines 2.6 Synthesis of Oxindoles 2.7 Synthesis of Indolines and Indoles 2.8 Synthesis of Imidazo[1,5-α]pyridines and Imidazoles 2.9 Synthesis of Imidazolones, Imidazolidinones, Oxazolones, and Oxazolidinones 2.10 Synthesis of Benzoxazoles, Oxazolines, and Isoxazolines 2.11 Synthesis of Furans and Dihydrofurans 2.12 Synthesis of Indolizines, Pyrazoles, and Triazolium Inner Salts 2.13 Synthesis of Sulfonated Benzothiophenes, Thiazoles, Dihydrothiazoles, and 1,3,4-Thiadiazoles 2.14 Synthesis of Lactones 3 Electrochemical Cascade Cyclization for the Construction of Carbocycles 3.1 Synthesis of Carbon Polycycles and Spiroindenes 3.2 Synthesis of Difluoroacyl (Hetero)arenes and Sulfonated Indenones 4 Conclusion",10.1055/a-2039-1728,2023-02-20,0.5948548890537634
Journal of Organic Chemistry,Concise Enantioselective Total Synthesis of Isopavine Alkaloids,"Herein, we report a concise asymmetric total synthesis of isopavine alkaloids, which feature a special azabicyclo[3.2.2]nonane tetracyclic skeleton. The key steps include iridium-catalyzed asymmetric hydrogenation of unsaturated carboxylic acids, Curtius rearrangement, and Eschweiler–Clarke methylation, which enable an enantioselective approach to isopavine alkaloids in 6–7 linear steps. Furthermore, for the first time, isopavine alkaloids, especially (−)-reframidine ( 3 ), are found to display effective antiproliferative effects on various cancer cell lines.",10.1021/acs.joc.2c02899,2023-03-09,0.5948474971157703
Tetrahedron,First total synthesis of the novel cytotoxic benzocycloheptenes (±)-deoxofaveline and (±)-faveline methyl ether,,10.1016/s0040-4039(00)92335-9,1992-01-01,0.5948389882962104
Journal of Organic Chemistry,Catalytic Enantioselective Synthesis of a Pyrrolizidine–Alkaloid-Inspired Compound Collection with Antiplasmodial Activity,"A novel enantioselective approach to the synthesis of a compound collection inspired by natural pyrrolizidine alkaloids was developed, employing an enantioselectively catalyzed 1,3-dipolar cycloaddition as the key step. The cycloadducts were obtained with excellent enantio- and diastereoselectivity. Biological evaluation of the resulting compound collection revealed that the compound class has multiple bioactivities, including activity against Plasmodium falciparum 3D7 and inhibition of Hedgehog signaling.",10.1021/acs.joc.7b03202,2018-02-20,0.5948373536549078
Journal of Organic Chemistry,"Collective Total Synthesis of Aculeatin A, B, D, E, and F","A collective convergent approach for the enantioselective total synthesis of aculeatins A, B, D, E, and F is presented, featuring [3 + 2]-cycloaddition, iron-mediated reductive N–O bond cleavage, and cascade spirocyclization. Moreover, this short six-step strategy is supplemented in synthesizing unnatural analogs of aculeatins such as 6- epi -aculeatin D, 6- epi -aculeatin E, and 6- epi -aculeatin F.",10.1021/acs.joc.4c03024,2025-02-05,0.5948369240679504
Synthesis,Facile and Efficient Synthesis of ido-Heptulosan via a Strategy Derived from Mo(VI)-Catalysed Reactions,"A simple and high-yielding method for the preparation of 2,7-anhydro-β-d - ido-heptulopyranose (IDO) is described. It utilises the ability of molybdate ions to create the conditions for the skeletal rearrangement in the molecule of 2-C-branched aldose. This evidence is used in the synthesis of IDO from 2-C-(hydroxymethyl)-2,3:5,6-di-O-isopropylidene-d-gulofuranose in one step. The title compound is obtained in 95% yield.",10.1055/s-2001-12773,2001-01-01,0.5948350219495218
Journal of Organic Chemistry,Intramolecular 5-<i>endo-</i>Trig Aminomercuration of β-Hydroxy-γ-alkenylamines:  Efficient Route to a Pyrrolidine Ring and Its Application for the Synthesis of (+)-Castanospermine and Analogues,"The intramolecular aminomercuration reaction of sugar-derived beta-hydroxy-gamma-alkenylamines 8a-c undergoes 5-endo-trig cyclization in high yield. The sugar-substituted pyrrolidines thus obtained were elaborated to the synthesis of polyhydroxylated indolizidine alkaloids, namely, castanospermine 1a, 1-epi-castanospermine 1b, and 8a-epi-castanospermine 1c, having promising glycosidase inhibitory activities.",10.1021/jo0601617,2006-05-18,0.5948341242681234
Tetrahedron,Towards the synthesis of chiral isochromanquinones. The use of Corey–Bakshi–Shibata reductions,,10.1016/s0040-4039(02)00759-1,2002-06-01,0.5948150683081886
Tetrahedron,Enantioselection via birch reduction-alkylation of a chiral anthranilic acid derivative. Synthesis of enantiomerically pure aminocyclohexanes,,10.1016/s0040-4039(00)98567-8,1985-01-01,0.5948103056027091
Synthesis,Synthetic Studies toward Ecteinascidin 743 (Trabectedin),An alternative synthetic route to an intermediate in the synthesis of ecteinascidin 743 has been established by using a Pictet–Spengler reaction and a Friedel–Crafts type reaction.,10.1055/s-0032-1316579,2012-07-06,0.5948100689957343
Tetrahedron,"Chiral synthesis of maconelliol: a novel cyclobutanoid terpene alcohol from pink hibiscus mealybug, Maconellicoccus hirsutus",,10.1016/j.tetlet.2004.10.131,2004-11-09,0.5948042038574181
Synlett,"General and Easy Access to 11-Substituted 4-Hydroxy-2,3,4,5-tetrahydro[1,4]diazepino[1,2-<i>a</i>]indol-1-one Derivatives","An efficient route to prepare the 4-hydroxy-2,3,4,5-tetrahydro[1,4]diazepino[1,2-a]indol-1-one scaffold is described. The key reactions of the synthesis are an iodolactonisation followed by a lactone-to-lactam rearrangement. Various 11-substituted derivatives were obtained by palladium-mediated cross-coupling reactions.",10.1055/s-2006-950249,2006-10-01,0.5947970709298697
European Journal of Organic Chemistry,DISTAL Dibromoresorcin[4]arenes Through Selective Deactivation: A Practical Optimization,"A simple and straightforward regioselective synthesis of distal disubstituted resorcin[4]arenes was developed, avoiding competing substitution patterns at an early stage via regioselective deactivation. Product limiting reaction steps were optimized by starting material recovery and by an improved protocol for ester cleavage while providing simple workup procedures throughout the synthesis without requiring column chromatography. The cyclizing acetalization of distal disubstituted resorcinarene octols proved to be a high yield process without oligomer formation, although less sterically controlled compared to the usual tetrabromo case.",10.1002/ejoc.202001031,2020-11-04,0.5947955442576299
European Journal of Organic Chemistry,Catalytic Asymmetric Friedel–Crafts Alkylation of Indole via In Situ Generated Indol‐2‐one,"Abstract An asymmetric Friedel–Crafts alkylation of indole with in situ generated indol‐2‐one from functionalized 3‐bromooxinidole catalyzed by chiral N,N’ ‐dioxide/Ni(BF 4 ) 2 has been developed. This protocol provides an efficient route to stereoselective construction of a series of 3‐substituted 3’‐indolyloxindoles bearing a quaternary carbon center in excellent yields and enantioselectivities (up to 99 % ee). In addition, the conversion of the resulted 3‐substituted 3’‐indolyloxindole to the key intermediate for the formal synthesis of (+)‐folicanthine was also demonstrated.",10.1002/ejoc.202300122,2023-02-21,0.5947949147888214
Organic Letters,"[1 + 2 + 3] Annulation as a General Access to Indolo[3,2-<i>b</i>]carbazoles: Synthesis of Malasseziazole C","A formal [1 + 2 + 3] annulation of methyleneindolinones with o-alkenyl arylisocyanides has been developed for the general and efficient synthesis of both symmetrical and unsymmetrical indolo[3,2- b]carbazoles. The chemoselectivity of this domino reaction was tuned by a tethered alkenyl group, which enables successive formation of three new bonds and two rings from readily accessible starting materials in a single operation. Furthermore, this methodology was used as a key step in the synthesis of the alkaloid malasseziazole C.",10.1021/acs.orglett.8b03646,2018-12-20,0.5947931967875949
Organic Letters,Total Synthesis of (−)-Disorazole C<sub>1</sub>,"Disorazoles represent a powerful class of highly potent antitubulin natural products isolated from myxobacteria. Herein, we describe a scalable and robust synthesis of (−)-disorazole C 1 with high stereoselectivity, featuring quite simple reaction conditions that can be used to produce large quantities of this remarkable biologically active compound.",10.1021/acs.orglett.1c01123,2021-05-26,0.5947928832701666
Journal of Organic Chemistry,Synthesis of Phidianidines A and B,"Reaction of a substituted indole-3-acetyl chloride with N-5-azidopentyl-N'-hydroxyguanidine generated a substituted 3-(5-azidopentylamino)-5-((indol-3-yl)methyl)-1,2,4-oxadiazole. Reduction of the azide with zinc and ammonium formate afforded the amine, which was elaborated to the guanidine, completing short and efficient syntheses of the cytotoxic natural products phidianidines A and B in 19% overall yield by a convergent route that will make analogues readily available for biological evaluation. Initial screening in the NCI 60 cell line at 10(-5) M indicated that the bromine on the indole is necessary for activity and that the amine precursor to phidianidine A is more potent than phidianidine A.",10.1021/jo300449n,2012-04-23,0.5947893573114291
Angewandte Chemie International Edition,Total Synthesis of Salinamide A: A Potent Anti‐Inflammatory Bicyclic Depsipeptide,It's swell! The first total synthesis of potent anti-inflammatory agent salinamide A was achieved. This synthesis features a concise elaboration of the phenylglycine-derived epoxide fragment and the identification of two possible macrolactamization sites (see scheme).,10.1002/anie.200800397,2008-03-28,0.5947885581275878
Tetrahedron,Aryl-coupling via “axially prostereogenic” lactones: First total synthesis of (+)-ancistrocladisine and (optionally) its atropisomer,,10.1016/s0040-4039(01)93754-2,1989-01-01,0.594783620757866
Organic Letters,A New Route to Bicyclo[1.1.1]pentan-1-amine from 1-Azido-3-iodobicyclo[1.1.1]pentane,"From a medicinal chemistry perspective, bicyclo[1.1.1]pentan-1-amine (1) has served as a unique and important moiety. Synthetically, however, this compound has received little attention, and only one scalable route to this amine has been demonstrated. Reduction of an easily available and potentially versatile intermediate, 1-azido-3-iodobicyclo[1.1.1]pentane (2), can offer both a flexible and scalable alternative to this target. Herein, we describe our scrutiny of this reportedly elusive transformation and report our ensuing success with this endeavor.",10.1021/ol500635p,2014-03-14,0.5947779347656837
Synthesis,"Synthesis of (+)-Canadensolide, (-)-Santolinolide A and (+)-Santolinolide B: The Imino-Claisen Reaction in Natural Product Synthesis","All articles of this category The iminoketene-Claisen reaction serves as a key step in an efficient asymmetric synthesis of (+)-canadensolide, (+)-santolinolide B and (-)-santolinolide A: Starting from D-mannitol an optically active N -allylacetamide was generated which was rearranged to the corresponding diastereomeric nitrile. After cyclization two optically active 4,5-difunctionalized γ-butyrolactones with defined configuration at the chiral centers were obtained. The syn-4,5 disubstituted lactone was used for the synthesis of (2 R ,3 S ,4 S )-(+)-canadensolide, the anti-4,5 difunctionalized lactone was employed in the synthesis of the (3 R ,4 S ,5 S )-(+)-santolinolide B and the (3 S ,4 S ,5 S )-(-)-santolinolide A.",10.1055/s-1993-26013,1993-01-01,0.5947769912010651
Synlett,Total Synthesis and Structure Revision of Saniculamoid D,"Abstract We present the first asymmetric total synthesis of the norsesquiterpenoid saniculamoid D, from a previously known pure chiral imide, with a longest linear sequence of seven steps. The key highlight of the synthesis is the formation of the bicyclo[3.1.0]hexane moiety through the Julia–Kocienski olefination and Hodgson cyclopropanation. Notably, the NMR spectra and specific rotation value of the synthesized structure did not agree with those of the natural compound. However, a meticulous comparison of the data prompted the reassignment of the correct structure of saniculamoid D, which now corresponds to the structure initially proposed for chromolaevanedione.",10.1055/a-2147-9454,2023-08-03,0.5947699915637951
Journal of the American Chemical Society,Quaternary Carbon as a Locus for Skeletal Disconnection. Total Synthesis of (±)-Tubingensin A Featuring Assembly of the Backbone Stereotriad Using a <i>Halo</i>-Prins/<i>Halo</i>-Nazarov Cascade,"High Resolution Image Download MS PowerPoint Slide The first successful fragment coupling/cationic cascade approach for the synthesis of a complex indoloditerpenoid tubingensin A is described. The synthesis is the first example of a novel disconnection strategy targeting a central quaternary carbon locus. A halo -Prins/ halo -Nazarov cationic cascade sequence enabled the rapid preparation of a complex intermediate as a single diastereomer, containing the vicinal quaternary centers found in the backbone stereotriad. This approach installed much of the complex carbon skeleton of tubingensin A in one step from fragment coupling of two simple reactants. To complete the synthesis, the indane ring system is converted to the target cis- decalin, preserving the integrity of the stereotriad. The isopropylidene fragment is appended in the endgame. The target is obtained in 15 fully diastereoselective steps from simple achiral materials. Investigation of the halo -Nazarov cyclization revealed fluxional behavior in the Friedel–Crafts termination step.",10.1021/jacs.5c06475,2025-06-16,0.5947674183595696
Tetrahedron,"An improved synthesis of 1α, 25-dihydroxyvitamin D A synthons",,10.1016/s0040-4039(00)96053-2,1987-01-01,0.5947664068730188
European Journal of Organic Chemistry,A Concise Catalytic Route to the Marine Sesquiterpenoids (–)‐Clavukerin A and (–)‐Isoclavukerin A,"Abstract Using a combined organocatalytic/metal‐catalyzed strategy, the enantiopure title hydroazulenes were prepared in only four steps from ( S )‐ and ( R )‐citronellal, respectively. A catalyst‐controlled diastereoselective Michael addition of these aldehydes to methyl vinyl ketone followed by chemoselective dibromoolefination and one‐pot Wittig olefination/alkyne formation afforded the key dienynes that underwent regioselective domino metathesis to yield the target natural products.",10.1002/ejoc.201001087,2010-09-29,0.5947537268124673
Journal of Organic Chemistry,"Highly Convergent, Stereospecific Synthesis of 11-<i>cis</i>-Retinoids by Metal-Catalyzed Cross-Coupling Reactions of (<i>Z</i>)-1-Alkenylmetals","A stereospecific synthesis of 11-cis-retinoids has as its key step the hitherto unexplored palladium-catalyzed cross-coupling of trans-trienyl electrophiles and (1Z,3E)-penta-1,3-dienyl boronates (a Suzuki-Miyaura reaction) or stannanes (a Stille reaction). This highly convergent approach constitutes the first application of cis-organometallic moieties to the synthesis of 11-cis-retinoids and represents a general, straightforward route to the visual chromophore.",10.1021/jo701664r,2007-11-15,0.5947521210461649
Synthesis,Asymmetric Synthesis of γ-Amino-Functionalised Vinyl Sulfones: De Novo Preparation of Cysteine Protease Inhibitors,"Abstract The enantioselective azo-based α-amination of an aldehyde followed by a Horner–Wadsworth–Emmons-based vinyl sulfone formation is reported. The thus obtained optically active N,N′-diprotected trans-(phenylsulfonyl)vinyl hydrazine products were then converted into the corresponding N-functionalised trans-(phenylsulfonyl)vinyl amines. Specifically, reaction of 4-phenylbutanal with di-tert-butyl azodicarboxylate (DBAD) in the presence of l- or d-proline, followed by addition of diethyl [(phenylsulfonyl)methyl]phosphonate, gave either enantiomer of di-tert-butyl trans-1-[5-phenyl-1-(phenylsulfonyl)pent-1-en-3-yl]hydrazine-1,2-dicarboxylate. The enantiomeric excesses of the (+)- and (–)-enantiomers prepared in this manner were in the range 86–89%. The conversion of these γ-hydrazino vinyl sulfones into the corresponding γ-amino-substituted compounds was achieved following a Boc deprotection, Zn reduction, N-functionalisation sequence. This three-step sequence was reasonably efficient (approx. 50%) and no erosion of enantiopurity was found to have taken place. The compounds accessed via this process include both enantiomers of tert-butyl trans-[5-phenyl-1-(phenylsulfonyl)pent-1-en-3-yl]carbamate and epimeric dipeptide mimetics including 4-methyl-N-{(S)-1-oxo-3-phenyl-1-[((S,E)-5-phenyl-1-(phenylsulfonyl)pent-1-en-3-yl)amino]propan-2-yl}piperazine-1-carboxamide (also known as K777).",10.1055/s-0041-1737764,2022-01-27,0.5947429091397916
Synlett,An Efficient Access to Conformationally Rigid Amino Acid Analogues with a Piperidine Skeleton,Two unnatural conformationally constrained cyclic amino acid derivatives with the piperidine skeleton were synthesized in enantiomerically pure forms. The key step in the synthesis of these amino acids is the highly diastereoselective functionalization of the oxo group in a 4-oxo-pipecolic acid derivative.,10.1055/s-0029-1219948,2010-05-25,0.5947200248771641
Tetrahedron,"Approaches to p-hydroxyphenoxymethylquinolines which avoid intermediate chloromethylquinolines for the synthesis of the LTD4 antagonist, RG 12525",,10.1016/s0040-4039(96)02361-1,1997-01-01,0.5947191332504937
Synthesis,Concise and Environmentally Friendly Asymmetric Total Synthesis of the Putative Structure of a Biologically Active 3-Hydroxy-2-piperidone Alkaloid,"An asymmetric total synthesis of stereoisomers of a putative structure of 3-hydroxy-2-piperidone alkaloid derivative is described. This route is not only concise and efficient but also is achieved under an environmentally friendly approach. To this end, a direct and double C–H oxidation reaction of simple benzylated piperidine and Baker’s yeast reduction of a carbonyl group allowed the rapid access to the optically enriched (S)-1-benzyl-3-hydroxy-2-piperidone in only three steps. The NMR data agreed with those obtained in the first total synthesis (and in discrepancy with the natural product), however, optical rotation did not match with both neither the natural and synthetic material.",10.1055/s-0037-1610089,2018-06-26,0.5947164895940386
Synlett,Synthesis of<i>N</i>-Substituted 3-Acylpyrroles by Intramolecular Cycloamination of 4-Amino-1-azabutadienes,All articles of this category A new synthesis of 3-acylpyrroles 4 is achieved by an exo-dig cyclization of 3-propargyl-4-amino-1-azabutadienes 3 . In situ reduction of the imine group remaining after the initial cyclization gives the 3-aminomethylpyrrole 6 .,10.1055/s-1990-21091,1990-01-01,0.5947113641335425
Synlett,Efficient Total Synthesis of (-)-Epilitsenolide C<sub>2</sub>and (-)-Isodihydro-mahubanolide B via a Modified Tungsten-Mediated Cycloalkenylation Reaction,All articles of this category An efficient method is developed for total synthesis of (-)-epilitsenolide C 2 and (-)-isodihydro-mahubanolide B based on a modified cycloalkenylation of chiral alkynyltungsten compounds. tungsten - cycloalkenylation - total synthesis,10.1055/s-2000-6759,2000-01-01,0.5947085882011749
Journal of Organic Chemistry,Total Synthesis of Pinnamine and Anatoxin-a via a Common Intermediate. A Caveat on the Anatoxin-a Endgame,"[reaction: see text] This paper describes the total synthesis of the naturally occurring alkaloids pinnamine (1) and anatoxin-a (2) from a common enantiomerically pure intermediate (7) easily available from pyroglutamic acid. The synthesis of enantiopure pinnamine proceeded in 10 steps and 4.8% overall yield, and the route was flexible enough to allow stereocontrolled access to a non-natural congener (5-epi-pinnamine) of the natural product. Intramolecular reaction of an N-acyl iminium ion was a key step in the synthesis of both pinnamine and anatoxin-a. However, in stark contrast to literature precedent, complete racemization was observed during the reaction of the N-acyliminium ion leading to the latter alkaloid.",10.1021/jo0506682,2005-06-15,0.5947041107806627
Synlett,"Efficient Synthesis of Novel Bridgehead-Substituted Bicyclo[3.2.1]octane-2,4-diones","We report the efficient synthesis of bridgehead-substituted bicyclo[3.2.1]octane-2,4-diones. The key step in their construction is a highly efficient intramolecular [3+2] cycloaddition between a nitrile oxide and an olefin. The reductive ring cleavage of the resulting dihydroisoxazole provides the desired bridgehead-­substituted bicyclo[3.2.1]octane-2,4-diones.",10.1055/s-0030-1258499,2010-07-16,0.5947013033710128
Tetrahedron,Asymmetric synthesis of the key intermediate of an SP antagonist RPR107880 using a base-catalyzed Diels–Alder reaction,,10.1016/s0040-4039(00)00555-4,2000-05-01,0.5947009572309006
European Journal of Organic Chemistry,Total Synthesis of Cristatic Acid Based on Late‐Stage Decarboxylative Allylic Migration and Biomimetic Aromatization of a Diketo Dioxinone,"Abstract A fifteen‐step synthesis of methyl cristatate is described. tert ‐Butyl‐[( E )‐6‐iodo‐3‐methylhex‐2‐enyloxy)]diphenylsilane, synthesized from geraniol, was coupled with 2‐(diethoxymethyl)‐4‐lithiofuran and transformed – by acetal hydrolysis, Wittig olefination, and desilylation – into a sesquiterpene furan alcohol. This alcohol was converted into methyl cristatate by sequential condensation with carbonyldiimidazole and the enolate dianion derived from 2,2‐dimethyl‐6‐(2‐oxopropyl)‐4 H ‐1,3‐dioxin‐4‐one and subsequent Pd 0 ‐catalyzed decarboxylative allylic migration, biomimetic aromatization, and transesterification with methanol.",10.1002/ejoc.201301102,2013-09-25,0.5946974985921126
Tetrahedron,"First synthesis of 3-aryl-5-dichloromethyl-2-pyrazolines. The electrochemical generation of 2,2-dichlorovinylacetophenones as a key step",,10.1016/j.tetlet.2004.09.101,2004-10-04,0.5946798123147277
European Journal of Organic Chemistry,Synthesis of a 3′‐Deoxy‐<i>C</i>‐Nucleoside Phosphonate Bearing 9‐Deazaadenine as Base Moiety,"Herein, the synthesis of the first example of a 3′‐deoxy‐5′‐phosphonate 2′[R] C‐nucleoside and its corresponding prodrug is presented. The developed route involves a reductive debromination at the 2′‐position of a suitably substituted 9‐deazaadenosine intermediate, followed by a stereoselective glycosylation at the 5′‐anomeric position to achieve the installation of the phosphonomethoxy functionality. The target compound with the desired configuration is formed upon base‐promoted epimerization at the 2′[S]‐position of the sugar moiety.",10.1002/ejoc.201800889,2018-09-19,0.5946794929804676
Journal of the American Chemical Society,Total Synthesis of Shishijimicin A,The total synthesis of the rare but extremely potent antitumor agent shishijimicin A has been achieved via a convergent strategy involving carboline disaccharide 3 and hydroxy enediyne thioacetate 4.,10.1021/jacs.5b05575,2015-07-02,0.5946700169306206
Organic Process Research & Development,"Process Development toward the Pilot Scale Synthesis of the Piperidine-Based Cocaine Analogue and Potent Dopamine and Norepinephrine Reuptake Inhibitor CTDP 31,446","(+)-Methyl 4β-(4-chlorophenyl)-1-methylpiperidine-3α-carboxylate hydrochloride (CTDP 31,446) is known as a dopamine reuptake inhibitor. This cocaine analogue lacking the tropane skeleton is being considered for potential treatment of cocaine addiction. Herein we report the development of a scalable process for the preparation of this compound. This study was mainly aimed at improving the process throughput, eliminating chromatographic purifications for the separation of (±)- 6 -cis isomer from (±)- 6 -trans isomer, and developing a robust crystallization for isolation of pure (±)- 6 -cis in a single crop with a good mass recovery. The process development work also highlights an efficient recycle of (±)- 6 -trans via a kinetic epimerization followed by crystallization of the resulting (±)- 6 -cis isomer. The resolution of (±)- 6 -cis and the crystallization of the final HCl salt were optimized and implemented to afford CTDP-31,446 with high purity and good mass recovery.",10.1021/op060114g,2006-08-19,0.5946667802064344
Synlett,A Novel Domino Route to Chiral Cyclobutanones and its Function as Cornerstone in the Synthesis of Versatile Natural Products,"All articles of this category A novel enantiocontrolled method for the synthesis of chiral cyclobutanones is described. This consists of the preparation of chiral cyclopropanols using a chiral oxathiane as a chiral auxiliary followed by enantiospecific expansion of the cyclopropane ring, domino asymmetric epoxidation and enantiospecific ring expansion (DAE-ERE) of cyclopropylideneethanols, and asymmetric dihydroxylation of the cyclopropylidene group followed by enantiospecific expansion of the resulting cyclopropanediols. Ortho -substituents of the aromatic ring have particularly strong effects on enantioselectivity in the DAE-ERE reactions of aromatic cyclopropylideneethanols. The resulting cyclobutanones are very versatile building blocks, as shown in the enantiocontrolled synthesis of various types of compounds such as pheromones, terpenes, and alkaloids. domino reaction - cyclopropylidene substituted alcohol - oxaspiropentane - chiral cyclobutanone - natural product synthesis",10.1055/s-1997-925,1997-08-01,0.594661357707048
Tetrahedron,Synthesis of a novel bifunctional chelating agent for actinium complexation,,10.1016/s0040-4039(00)01208-9,2000-09-01,0.5946598950943336
Angewandte Chemie International Edition,"Asymmetric Total Synthesis of Shizukaol J, Trichloranoid C and Trishizukaol A","Abstract The asymmetric total synthesis of three lindenane sesquiterpenoid oligomers, shizukaol J, trichloranoid C and trishizukaol A, has been accomplished concisely in 15, 16 and 18 longest linear steps, respectively. The expeditious construction of molecular architectures was facilitated by Nelson's catalytic asymmetric ketene–aldehyde cycloaddition, a sequence of allylic alkylation/reduction/acidic cyclization to forge a lactone, and a double aldol condensation cascade to construct the 5/6 bicyclic system. Diastereoselective nucleophilic substitution promoted by a phase transfer catalyst constructed the C 11 quaternary stereogenic center, thus prompting synthetic efficacy toward shizukaol J. The synthesis of trichloranoid C and trishizukaol A was achieved after a cascade involving furanyl diene formation and a Diels–Alder reaction, as well as a one‐pot sequence involving furan oxidation and global deprotection. Furthermore, our biological evaluation revealed that two compounds exhibited unexpected toxicity against tumor cell lines.",10.1002/anie.202200258,2022-02-01,0.594657863694788
Organic Letters,Synthesis of Dimethyl Sulfomycinamate,"[reaction: see text] Dimethyl sulfomycinamate, the oxazole-thiazole-pyridine product generated in the methanolysis of the thiopeptide antibiotic sulfomycin I, is prepared in 13 steps and 8% overall yield by the Bohlmann-Rahtz heteroannulation of 1-(oxazol-4-yl)enamines and methyl 4-(trimethylsilyl)-2-oxobut-3-ynoate.",10.1021/ol0357144,2003-10-21,0.5946569304728486
European Journal of Organic Chemistry,"Asymmetric Synthesis of 1-Aryl-1,2,3,4-tetrahydroisoquinolines. Part 2. Preparation of Chiral 2-(2-Bromobenzyl)-1,3-dioxolanes and Their Addition to Acylimines.",,,1998-01-01,0.5946553630137497
Tetrahedron,Synthetic study of gymnocin-A: synthesis of the ABC ring fragment,,10.1016/j.tetlet.2014.10.014,2014-10-24,0.5946539594906053
Tetrahedron,Synthetic study of aquayamycin. Part 2: Synthesis of the AB ring fragment,,10.1016/s0040-4039(00)01479-9,2000-10-01,0.5946539594906053
Journal of the American Chemical Society,Optically Active Calixarenes Conduced by Methylene Substitution,"The first method for the synthesis of optically active calix[4]arenes that are chiral as a result of substitution on the methylene bridges is described. The key step in the synthesis involves the reaction of a biscarbene complex with a diyne, which generates two of the benzene rings and the macrocyclic ring of the calix in a single transformation. The utility of this triple annulation process is demonstrated in the synthesis of di- and tetramethoxycalix[4]arenes. The flexibility of this synthetic approach is demonstrated by the synthesis of two diastereomers of the tetramethoxycalix[4]arenes in which each is synthesized in a stereoselective fashion by proper control of the absolute configurations of the methoxy groups in the biscarbene complex and in the diyne.",10.1021/ja905990u,2009-11-24,0.5946418930203525
Tetrahedron,Synthesis of pinnaic acid; Asymmetric construction of spirocyclic core,,10.1016/s0040-4039(99)00578-x,1999-04-01,0.5946406038202418
Journal of Organic Chemistry,Total Synthesis of (−)-Zearalenone and (−)-Zearalanone: A Macrocyclization Strategy by Ni/Zr/Cr-Mediated Reductive Ketone Coupling,"The total synthesis of the resorcylic acid lactones (−)-zearalenone and (−)-zearalanone is described. Our synthetic strategy relies on Ni-, Zr-, and Cr-mediated intramolecular reductive ketone coupling to create 14-membered macrolactones. Notably, the use of CrCl 2 in addition to Ni/Zr-mediated reductive ketone coupling conditions was key for the success of the macrocyclization.",10.1021/acs.joc.4c01793,2024-09-10,0.5946316862329706
Tetrahedron,A direct route to terpene isothiocyanates,,10.1016/s0040-4039(00)61683-0,1993-10-01,0.5946315416377761
Organic Process Research & Development,Some Items of Interest to Process R&amp;D Chemists and Engineers,"An expeditious synthetic approach to a chiral phenol, a key building block in the preparation of a series of drug candidates, is reported by Caille and co-workers at Amgen (J.Org.Chem.2011, 76, 5198À5206).The strategy includes a cost-effective and readily scalable route to 2,2-dimethylcyclopentanone from isobutyronitrile.The sterically hindered and enolizable 2,2-dimethylcyclopentanone was subsequently employed in a challenging Grignard addition mediated by LaCl 3 3 2LiCl.A novel preparation of the lanthanide reagent required for this transformation is also described.To complete the process, a highly enantioselective Rh-catalyzed hydrogenation afforded the target chiral phenol.The importance of the phenol group to the success of this asymmetric transformation is discussed. ' PHENYLGLYCINE-DERIVED CHIRAL SULFINYL TRANSFER AGENTChiral sulfinyl-containing reagents, such as sulfoxides and sulfinamides, have been recognized as useful tools in the asymmetric synthesis of complex organic molecules.Although the power of chiral sulfinyl reagents in synthetic chemistry has long been recognized, methods for their synthesis have emerged slowly.Now Han and co-workers at Boehringer Ingelheim report on a new chiral sulfinyl transfer auxiliary derived from readily available phenylglycine (J.Org.Chem.2011, 76, 5480À5484).This auxiliary can be utilized to synthesize a diverse array of alkyland arylsulfinamides and sulfinylferrocenes in high yields and excellent ee's.The desired products are produced in a one-pot sequence from the oxathiazolidine 2-oxide by two sequential nucleophilic additions that proceed in a stereospecific manner.",10.1021/op200215n,2011-08-31,0.5946185270618104
Tetrahedron,A short and efficient synthesis of echiguanines A and B: Potent inhibitors of phosphatidylinositol-4-kinase,,10.1016/s0040-4039(00)76939-5,1994-07-01,0.5946106932553448
Journal of Organic Chemistry,"Facile Synthesis of 1,3,7-Trihydroxyxanthone and Its Regioselective Coupling Reactions with Prenal:  Simple and Efficient Access to Osajaxanthone and Nigrolineaxanthone F","A facile five-step synthesis of naturally occurring 1,3,7-trihydroxyxanthone has been described starting from 1,3,5-trimethoxybenzene via NBS-induced nuclear bromination, lithiation followed by an in situ benzoylation with methyl 2,5-dibenzyloxybenzoate, selective deprotection of the two benzyl groups, base-catalyzed intramolecular cyclization, and demethylations pathway with 62% overall yield. The regioselective coupling reactions of 1,3,7-trihydroxyxanthone with prenal in the presence of calcium hydroxide at room temperature and under thermal conditions at 140-150 degrees C have been demonstrated to exclusively obtain the natural products osajaxanthone in 75% yield and nigrolineaxanthone F in 98% yield, respectively.",10.1021/jo0606655,2006-05-20,0.5946004552496776
Tetrahedron,A key intermediate for the synthesis of maytansine and related antitumor agents,,10.1016/s0040-4039(01)85449-6,1978-01-01,0.5945995860160952
Tetrahedron,Synthesis of cyclopropanols via acyloxycarbene intermediates,,10.1016/s0040-4039(00)93050-8,1976-09-01,0.5945938744920016
Tetrahedron,Synthesis of estrone intermediates,,10.1016/s0040-4039(00)71565-6,1967-01-01,0.5945938744920016
Synthesis,Synthesis of Prostanoid Intermediates,,10.1055/s-1977-24484,1977-01-01,0.5945938744920016
Synthesis,Enantioselective Synthesis ofFlavan-3-ols Using a Mitsunobu Cyclization,"The synthesis of four flavan-3-ols with different substitution patterns and electron densities has been achieved in high stereo- and regioselectivity by a one-step Mitsunobu reaction from the corresponding diols, which were prepared by enantioselective Sharpless dihydroxylation of suitable olefins. The six-membered flavan-3-ols were the only cyclization products and the theoretically possible formation of five-membered rings during the Mitsunobu cyclization was not observed. The flavanols are important starting materials for the synthesis of dimers such as the procyanidins or other coupling products such as the flavan part of the potent DNA polymerase β inhibitor myristinin A. The enantioselectivities of both the Sharpless dihydroxylation and the Mitsunobu cyclization steps were monitored by chiral HPLC.",10.1055/s-0028-1083361,2009-02-11,0.5945901890039771
Organic Letters,Synthesis of Two Hyaluronan Trisaccharides,"[formula: see text] The synthesis of two hyaluronan trisaccharides, methyl O-(beta-D-glucopyranosyluronic acid)-(1,3)-O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-(1,4)-O-beta-D- glucopyranosiduronic acid and methyl O-(2-acetamido-2-deoxy-beta-D-glucopyranosyl)-(1,4)-O-beta- D-glycopyranosyluronic acid)-(1,3)-O-(2-acetamido-2-deoxy-beta-D-glucopyranoside, are described. Construction of the target molecules was achieved though a combination of the phenyl sulfoxide and trichloroacetimidate glycosylation methodologies. This is the first report on the synthesis of the beta-methyl derivatives, which represent the smallest fragments that incorporate all the structural features of polymeric hyaluronan.",10.1021/ol0057075,2000-04-06,0.5945885986568102
Journal of Organic Chemistry,Synthesis of Undeculofuranoside Derivatives of the Herbicidins and of Analogs,"The condensation of 3-O-(tert-butyldimethylsilyl)-5-deoxy-1,2-O-isopropylidene-alpha-D-xylo- hexodialdo-1,4-furanose (obtained in six steps (35%) from D-glucurono-6,3-lactone) with the lithium enolate of (+/-)6-endo-chloro-5-endo-(methoxymethoxy)-7-oxabicyclo[2.2.1]heptan-2-o ne (derived in six steps (25%) from the Diels-Alder adduct of furan to 1-cyanovinyl acetate) was highly exo face selective giving two major aldols that were separated readily. One of them was converted to 6,10-anhydro-5-deoxy-1,2-O-isopropylidene-9-O-(methoymethyl)-alpha-D-ara bino-L-ido-7-undeculofuranose-(1,4)-pyranose-(7,3), a semiprotected form of the long-chain carbohydrate moiety of the herbicidins. The synthesis implies the acid-promoted isomerization of 10,11-anhydro-5,7-dideoxy-1,2-O-isopropylidene-9-O-(methoxymethyl)-7-C-[ (2-nitrophenyl)selenomethyl]-beta-L-ido-L-ido-undecofuranose.",10.1021/jo00123a021,1995-09-01,0.5945757954894723
Journal of Organic Chemistry,"New Synthetic Approaches to Polycyclic Aromatic Hydrocarbons and Their Carcinogenic Oxidized Metabolites:  Derivatives of Benzo[<i>s</i>]picene, Benzo[<i>r</i><i>st</i>]pentaphene, and Dibenzo[<i>b</i>,<i>d</i><i>ef</i>]chrysene","A new synthetic approach to polycyclic aromatic compounds is described that entails in the key steps double Suzuki coupling of PAH bisboronic acid derivatives with o-bromoaryl aldehydes to furnish aryl dialdehydes that are converted to larger polycyclic aromatic ring systems by either (a) conversion to diolefins by Wittig reaction followed by photocyclization or (b) reductive cyclization with triflic acid and 1,3-propanediol. This synthetic method provides convenient access to as many as three different polycyclic aromatic ring systems from a single Suzuki coupled intermediate. It was utilized to synthesize substituted derivatives of benzo[s]picene, benzo[rst]pentaphene, dibenzo[b,def]chrysene, and 13,14-dihydro-benz[g]indeno[2,1-a]fluorene, as well as the putative carcinogenic bisdihydrodiol metabolites of benzo[s]picene, benzo[rst]pentaphene, and dibenzo[b,def]chrysene.",10.1021/jo9918044,2000-05-31,0.5945754485956215
Synlett,Novel Synthetic Method of 2-(2-Oxoethyl)-1H-indole-3-carbaldehydes,"The smooth and regioselective synthesis of 2-(2-oxo­ethyl)-1H-indole-3-carbaldehydes via silver-catalyzed 6-endo-dig acetalization-cyclization reaction followed by immediate hydrolysis of the unstable 1-alkoxypyrano[4,3-b]indole intermediates is described.",10.1055/s-0030-1260317,2011-09-19,0.5945728545064622
Journal of Organic Chemistry,"Synthesis of α-, β-, and γ-Carbolines via Intramolecular Cyclization of Azidomethyl(indolyl)acrylates Involving PIFA-BF<sub>3</sub>·OEt<sub>2</sub>/DBU-Mediated Cyclization as well as Thermolysis Approaches","-mediated intramolecular cyclization of isomeric azidomethyl(indolyl)acrylates. Alternately, 1,5,7-triazabicyclo[4.4.0]dec-5-ene/1,8-diazabicyclo(5.4.0)undec-7-ene (TBD/DBU)-mediated Michael addition followed by intramolecular cyclization of isomeric 2/3-(azidomethyl)indol-3/2-yl)acrylates also furnished the respective β- and γ-carboline derivatives. Unexpectedly, the thermolysis of 2-(azidomethyl)-3-(indol-3-yl)acrylates led to the formation of ethyl 5-(2-(phenylsulfonamido)aryl)nicotinates along with γ-carbolines, via nitrene insertion followed by rearrangement and cyclization. The isomeric 2-(azidomethyl)-3-(indol-2-yl)acrylate upon thermolysis led to the expected δ-carboline. Thermal intramolecular nitrene insertion reaction could also be extended for accessing pyrido benzothiophene, pyrido thiophene, and quinoline.",10.1021/acs.joc.4c00571,2024-07-02,0.5945716811959554
Organic Letters,"Approaches to Polycyclic 1,4-Dioxygenated Xanthones. Application to Total Synthesis of the Aglycone of IB-00208","Hexacyclic xanthone natural products such as IB-00208 present a formidable challenge in organic synthesis. A new approach to polycyclic 1,4-dioxygenated xanthones from benzocyclobutenones has been developed and applied to the first total synthesis of the aglycone of IB-00208. The 22-step synthesis features an acetylide stitching process that joins an aryl aldehyde with an angularly fused benzocyclobutenone, which was prepared by a ring-closing metathesis reaction. The resulting acetylenic benzocyclobutenone diol underwent a Moore rearrangement to give an intermediate that was further elaborated to the aglycone of IB-00208 as a mixture of hydroquinone-quinone tautomers.",10.1021/ol503336t,2014-12-16,0.5945670076965458
Organic Letters,A Chiral Phosphoramidite Reagent for the Synthesis of Inositol Phosphates,"There is a paucity of chiral phosphoramidite reagents or chiral catalysis methods for the synthesis of biologically relevant inositol phosphates. A new C2-symmetrical chiral phosphoramidite has been developed and successfully applied to the synthesis of a set of chiral inositol bisphosphates. The reagent allowed bis-phosphorylation and chiral resolution, resulting in a concise synthetic route, thus expanding the toolbox available for the preparation of biologically relevant inositol phosphates in high optical purity.",10.1021/acs.orglett.6b01374,2016-06-22,0.5945614952984165
Journal of Organic Chemistry,Insights Derived from the Synthesis of a Complex Core 2 Glycan,"We describe the synthesis of a benzoyl-based C2- O -sLe X -Thr-COOH building block devoid of any aglycone transfer or orthoester-formed byproducts. The absence of byproducts was achieved in the course of both [1 + 1] glycosylation reactions with thiophenol aglycone containing galactose acceptors, as well as a [2 + 2] glycosylation in the presence of a p -methoxy benzyl containing glucosamine-fucose disaccharide. We also report an efficient [2 + 1 + 1] synthesis of a peracetylated sLe X en route to a peracetylated C2- O -sLe X -Thr-COOH. While the total synthesis of the latter compound was recently reported by a related route, the divergent [2 + 1 + 1] synthesis provided good reaction yields for each step of the sequence, establishing this scheme as an alternate approach to the peracetylated C2- O -sLe X -Thr-COOH. Importantly, the current report details the role of a variety of hydroxy-protecting groups, including acetyl, benzoyl, p -methoxy benzyl, and naphthylmethyl that may be considered in designing a route to this complex Core 2 glycan. While we have previously described the use of more glycosylation-friendly naphthylmethyl protecting groups, the current synthesis used p -methoxy benzyl protecting groups with excellent reaction yields, demonstrating the feasibility of applying this side reaction-prone protecting group for this challenging synthesis.",10.1021/acs.joc.4c01345,2024-08-01,0.5945599491181596
Organic Letters,Total Synthesis and Structural Revision of Monocillin VII,The first asymmetric total synthesis of macrolactone monocillin VII and its C-10' epimer was achieved starting from a known chiral pure epoxide in 16 longest linear sequences. The present synthesis highlights the macrolactone formation involving an alkyne-dicobalt carbonyl complex under De Brabander's conditions followed by an unexpected regioselective hydration. The asymmetric total synthesis resulted in the revision of the configuration at C10' and reassignment of the absolute configuration of the natural product.,10.1021/acs.orglett.9b02075,2019-07-23,0.5945537934737851
Organic Letters,Synthesis of an A−E Gambieric Acid Subunit with Use of a <i>C</i>-Glycoside Centered Strategy,"This paper describes our synthesis of the A-E subunit of gambieric acid (GA) in addition to the synthesis of the A-ring and the C-E tricycle. The use of an enol ether-olefin RCM strategy to couple the A and C-E subunits and, in the process, generate the B-ring is noteworthy.",10.1021/ol0707970,2007-05-01,0.5945500529167667
Angewandte Chemie International Edition,Total Synthesis and Structural Reassignment of (+)‐Dictyosphaeric Acid A: A Tandem Intramolecular Michael Addition/Alkene Migration Approach,The acid test? The synthetic route to the title compound features a Z-selective ring-closing metathesis reaction and an E-selective tandem intramolecular Michael addition/alkene migration sequence as the key transformations. The stereochemical configuration of the product was reassigned based on NMR studies.,10.1002/anie.201002416,2010-06-25,0.5945447802476229
Tetrahedron,Synthesis with organoboranes. 21. Synthesis of α- and gd-bamascone,,10.1016/s0040-4039(00)85153-9,1986-01-01,0.5945430451857794
Tetrahedron,Highly diastereocontrolled synthesis of the C1–C25 domain of sanglifehrin A,,10.1016/s0040-4039(00)00504-9,2000-05-01,0.5945398122963035
Tetrahedron,Synthesis of a highly branched C30 sedimentary hydrocarbon,,10.1016/s0040-4039(00)82128-0,1988-01-01,0.5945398122963035
Tetrahedron,Synthesis of diatropic highly benzannelated annulenes.,,10.1016/s0040-4039(01)92439-6,1981-01-01,0.5945398122963035
Tetrahedron,A highly stereocontrolled synthesis of (−)-kanshone a,,10.1016/0040-4039(91)80129-t,1991-12-01,0.5945398122963035
Angewandte Chemie International Edition,Total Synthesis of Vancomycin Aglycon—Part 3: Final Stages,"A triazene-based synthetic strategy for the construction of the complex biaryl ethers and a Suzuki coupling reaction were the key steps in the synthesis of precursor 1 of the aglycon of vancomycin, which already contains the complete skeleton of the target compound. The cleavage of the triazene unit from the D ring and the removal of the other protecting groups led to the aglycon of vancomycin. These strategies should be particularly valuable for the synthesis of other naturally occurring glycopeptide antibiotics and offer opportunities for the synthesis of combinatorial libraries of compounds of the vancomycin family for chemical biology studies.",10.1002/(sici)1521-3773(19981016)37:19<2717::aid-anie2717>3.3.co;2-9,1998-10-16,0.5945224441167777
Angewandte Chemie International Edition,Total Synthesis of Vancomycin Aglycon—Part 3: Final Stages,"A triazene-based synthetic strategy for the construction of the complex biaryl ethers and a Suzuki coupling reaction were the key steps in the synthesis of precursor 1 of the aglycon of vancomycin, which already contains the complete skeleton of the target compound. The cleavage of the triazene unit from the D ring and the removal of the other protecting groups led to the aglycon of vancomycin. These strategies should be particularly valuable for the synthesis of other naturally occurring glycopeptide antibiotics and offer opportunities for the synthesis of combinatorial libraries of compounds of the vancomycin family for chemical biology studies.",10.1002/(sici)1521-3773(19981016)37:19<2717::aid-anie2717>3.0.co;2-i,1998-10-16,0.5945224441167777
Synthesis,"Synthesis of 2,24-Diene-12,13,15,16,34,35,37,38-octaphenyl[4.4]triphenylparacyclophane","Abstract A new octaphenyl[4.4]triphenylparacyclophanediene was readily synthesized in six steps from p-xylene via the installment of bromine atoms, replacement with a vinyl group, carbonylative coupling, intermolecular followed by intramolecular double Grubbs olefin metathesis, Knoevenagel condensation, and Diels–Alder cycloaddition. The belt-shaped structure and trans-stereochemistry of the alkene moieties of the octaphenyl[4.4]triphenylparacyclophane and a synthetic intermediate, 2,21-dioxo-11,30-diene[3.4.3.4]paracyclophane, were determined by X-ray crystallography. The synthetic methodology leading to octaphenyl[4.4]triphenylparacyclophane is applicable for the synthesis of substituted triphenylparacyclophanes and possibly their corresponding bis-hexabenzocoronenylparacyclophanes via a Scholl–Mullen oxidative aryl-aryl coupling reaction.",10.1055/a-1479-6611,2021-04-12,0.5945215529951078
Tetrahedron,"Reduction of the indole ring system: synthesis of 4,5,6,7-tetrahydroindoles",,10.1016/s0040-4039(99)01687-1,1999-11-01,0.5945131166059519
Organic Letters,Stereoselective Synthesis of Substituted γ-Butyrolactones by the [3 + 2] Annulation of Allylic Silanes with Chlorosulfonyl Isocyanate:  Enantioselective Total Synthesis of (+)-Blastmycinone,[structure: see text]. A stereoselective synthesis of gamma-butyrolactones by the [3 + 2] annulation of allylic silanes with N-chlorosulfonyl isocyanate (CSI) was developed. An enantioselective total synthesis of (+)-blastmycinone was accomplished using this annulation as the key step.,10.1021/ol0069960,2001-02-14,0.5945005504177506
Journal of Organic Chemistry,"A Flexible Enantioselective Total Synthesis of Diospongins A and B and Their Enantiomers Using Catalytic Hetero-Diels−Alder/Rh-Catalyzed 1,4-Addition and Asymmetric Transfer Hydrogenation Reactions as Key Steps",A unified enantioselective route to total synthesis of diospongins A and B and their enantiomers has been developed employing achiral starting materials. All three stereocenters were introduced by means of catalytic reactions.,10.1021/jo901739y,2009-10-09,0.5944952401476646
Journal of Organic Chemistry,"A New Route toward 4-Substituted Pyrazino[2,1-<i>b</i>]quinazoline-3,6-dione Systems. Total Synthesis of Glyantrypine","Treatment of sodium N-(o-azidobenzoyl)aminoacylglycinates 8 with acetic anhydride afforded 1-acetyl-4-(o-azidobenzoyl)-2,5-piperazinediones 7, with complete retention of the stereochemistry. The intramolecular aza Wittig reactions of compounds 7 in the presence of tributylphosphine followed by deacetylation gave 1,2-unsubstituted pyrazino[2,1-b]quinazoline-3,6-diones 1. This route was adapted to the synthesis of both enantiomers of the alkaloid glyantrypine.",10.1021/jo991626e,2000-02-24,0.5944905437562403
Synlett,A Practical Synthesis of Sugar-Derived Cyclic Nitrones: Powerful Synthons for the Synthesis of Iminosugars,"Sugar-derived cyclic nitrones were synthesized from the corresponding aldoses through an efficient and practical procedure involving a seven-step reaction sequence in good to excellent overall yield (10-42%). This synthetic strategy, requiring only inexpensive reagents, is easy to perform and hence suitable for large-scale preparations.",10.1055/s-0029-1219189,2010-01-11,0.5944900673588573
Organic Letters,"Expedient Route to the Tigliane-Daphnane Skeleton via Oxonium Ylide [1,2]-Shift","A short, stereoselective approach to the fused tricyclic carbon skeleton found in the tigliane and daphnane classes of diterpene natural products is described. Convergent coupling of the A- and C-rings, followed by diastereoselective cerium enolate addition and formation of a double acetal set the stage for generation of an oxonium ylide via a transient metallocarbene. An efficient Stevens [1,2]-shift furnished the 7-membered B-ring, possessing the bridgehead oxygenation pattern found in the natural systems.",10.1021/ol102953s,2011-01-11,0.5944888045002146
Journal of Organic Chemistry,"Divergent Strategy for the Diastereoselective Synthesis of the Tricyclic 6,7-Diaryltetrahydro-6<i>H</i>-benzo[<i>c</i>]chromene Core via Pt(IV)-Catalyzed Cycloaddition of <i>o</i>-Quinone Methides and Olefin Ring-Closing Metathesis","A divergent strategy for the synthesis of the tricyclic 6,7-diaryltetrahydro-6 H -benzo[ c ]chromene core was successfully developed. The 2,3-trans, 2,4-cis trisubstituted chroman moiety was formed via highly efficient and stereoselective Pt(IV)-catalyzed cycloaddition reactions of the corresponding quinone methides with chalcones. Subsequent steps provided the common diene alcohol, which underwent BF 3 ·Et 2 O-mediated Et 3 SiH reduction and olefin ring-closing metathesis (RCM) using Ru(II) catalysts. The sequence of the final two steps provided a handle to diversify the stereochemical outcomes at C6 as well as C10a.",10.1021/acs.joc.6b03086,2017-02-10,0.594487882513215
Journal of Organic Chemistry,K<sub>2</sub>S<sub>2</sub>O<sub>8</sub>-Mediated Synthesis of Highly Functionalized Pyrroles via Oxidative Self-Dimerization of <i>N</i>-Propargylamines,"An efficient methodology has been developed for the synthesis of tetra- and pentasubstituted pyrroles via oxidative self-dimerization of N -propargylamines catalyzed by silver benzoate in the presence of K 2 S 2 O 8 in good yields. The protocol provides a simple route for the synthesis of both tetra- and pentasubstituted pyrroles with two carbonyl groups in the side chain. The methodology can be extended toward the synthesis of pyrrolo[3,4- d ]pyridazine.",10.1021/acs.joc.1c00471,2021-08-31,0.5944878765011934
Tetrahedron,Synthetic studies on brevetoxin-B. Part 3: Stereoselective synthesis of the IJK-ring system,,10.1016/s0040-4039(00)01339-3,2000-09-01,0.5944859875772542
Tetrahedron,Synthetic studies on enfumafungin: stereoselective synthesis of the CD ring segment,,10.1016/j.tetlet.2016.09.057,2016-09-20,0.5944859875772542
Tetrahedron,Synthetic studies on brevetoxin-B. Part 2: Stereoselective synthesis of the EFG-ring system,,10.1016/s0040-4039(00)01340-x,2000-09-01,0.5944859875772542
Tetrahedron,Synthetic studies on brevetoxin-B. Part 1: Stereoselective synthesis of the ABC-ring system,,10.1016/s0040-4039(00)01341-1,2000-09-01,0.5944859875772542
European Journal of Organic Chemistry,"Diastereo- and Enantioselective Synthesis ofN-Protected 2-Amino 1,4-Diols by an Oxa Michael Addition/1,3-Dipolar Cycloaddition Protocol","An enantioselective synthesis of N-protected amino diols has been accomplished by employing a diastereoselective inter- and intramolecular 1,3-dipolar cycloaddition reaction of optically active nitrile oxides as a key step. The nitro alkane starting materials were obtained by diastereoselective oxa Michael addition of (1R,2S)-(–)-N-formylnorephedrine (1) to aliphatic (E)-nitro alkenes 2, 6a, b (de = 96 – ≥ 98%). Subsequent diastereo- and regioselective cycloaddition reactions to highly substituted 4,5-isoxazolines 5a–e, 8a, b (52-81%) and reductive ring opening led – after cleavage of the auxiliary – to amino diols 13, 14 in good overall yields (27-40%, over five steps) and with excellent diastereomeric and enantiomeric excesses (de,ee ≥ 96%).",10.1002/(sici)1099-0690(199809)1998:9<1793::aid-ejoc1793>3.0.co;2-9,1998-09-01,0.5944853040409785
Angewandte Chemie International Edition,"A Formal Enantiospecific Synthesis of 7,20‐Diisocyanoadociane","7,20-Diisocyanoadociane (DICA) is a potent antimalarial isocyanoterpene endowed with a fascinating tetracyclic structure composed of fused chair cyclohexanes. We report a highly stereocontrolled synthesis of a late-stage intermediate, the ""Corey dione"", from which DICA has been made previously. This formal synthesis features a rapid buildup of much of the complexity of the target through a sequence of enone tandem vicinal difunctionalization, Friedel-Crafts cyclodehydration, and sequential stereocontrolled reductions. Most importantly, this success establishes the broader feasibility of our previously developed general synthesis approach to the isocyanoterpene family and provides a blueprint for a very direct synthesis of DICA and related natural products.",10.1002/anie.201603581,2016-05-10,0.594475173885252
Organic Letters,"Stereodivergent Strategy in Structural Determination: Asymmetric Total Synthesis of Garcinol, Cambogin, and Related Analogues","The asymmetric total synthesis of five biologically significant polycyclic polyprenylated acylphloroglucinols (PPAPs), including garcinol and cambogin, was achieved through a highly diastereoselective and stereodivergent strategy. Along the way, an efficient cascade Dieckmann cyclization was employed to construct the bicyclo[3.3.1]nonane core in one step. The synthesis provided a general approach toward the chiral endo -type B PPAPs and their C-30 diastereomers in a single sequence, which resolved the challenges of the absolute configuration determination/structural revision of PPAPs bearing exocyclic stereocenters.",10.1021/acs.orglett.1c01139,2021-05-24,0.5944737217965951
Tetrahedron,"Toward the total synthesis of scytophycins: Synthesis of the C7–C21 fragments of scytophycins A, B, and C",,10.1016/j.tetlet.2022.154250,2022-11-16,0.594472127811938
Journal of Organic Chemistry,Total Synthesis of (±)-Spiroaxillarone A,"Spiroaxillarone A, a novel and unique spirocyclic dinaphthalene natural product with significant antimalarial activity, was regioselectively synthesized from tetrahydrocurcumin in five steps with an overall 10% yield. Key features of the synthesis involved an oxidized free radical cycloaddition to build the spiro ring central skeleton and an oxidized dehydrogenation to introduce two double bonds via enol silicon ether from diketones.",10.1021/acs.joc.0c02894,2021-03-01,0.5944690974165409
Journal of the American Chemical Society,Total Asymmetric Synthesis of the Putative Structure of the Cytotoxic Diterpenoid (−)-Sclerophytin A and of the Authentic Natural Sclerophytins A and B,"An enantioselective synthetic route to the thermodynamically most stable diastereomer of the structure assigned to sclerophytin A (5) has been realized. The required tricyclic ketone 33 was prepared by sequential Tebbe-Claisen rearrangement of lactones 29 and 30, which originated from the Diels-Alder cycloaddition of Danishefsky's diene to (5S)-5-(d-menthyloxy)-2(5H)-furanone (14). An allyl and a cyano group were introduced into the resulting adduct by means of stereocontrolled allylindation under aqueous Barbier-like conditions and by way of cyanotrimethylsilane, respectively. Following stereocontrolled nucleophilic addition of a methyl group to 33, ring A was elaborated by formation of the silyl enol ether, ytterbium triflate-catalyzed condensation with formaldehyde, O-silylation, and Cu(I)-promoted 1,4-addition of isopropylmagnesium chloride. The superfluous ketone carbonyl was subsequently removed and the second ether bridge introduced by means of oxymercuration chemistry. Only then was the exocyclic methylene group unmasked via elimination. An alternative approach to the alpha-carbinol diastereomer proceeds by initial alpha-oxygenation of 37 and ensuing 1,2-carbonyl transposition. Neither this series of steps nor the Wittig olefination to follow induced epimerization at C10. Through deployment of oxymercuration chemistry, it was again possible to elaborate the dual oxygen-bridge network of the target ring system. Oxidation of the organomercurial products with O(2) in the presence of sodium borohydride furnished 72, which was readily separated from its isomer 73 after oxidation to 61. Hydride attack on this ketone proceeded with high selectivity from the beta-direction to deliver (-)-60. Comparison of the high-field (1)H and (13)C NMR properties and polarity of synthetic 5 with natural material required that structural revision be made. Following a complete spectral reassessment of the structural assignments to many sclerophytin diterpenes, a general approach to sclerophytin A, three diastereomers thereof, and of sclerophytin B was devised. The presence of two oxygen bridges as originally formulated was thereby ruled out, and absolute configurations were properly determined. Key elements of the strategy include dihydroxylation of a medium-ring double bond, oxidation of the secondary hydroxyl in the two resulting diols, unmasking of an exocyclic methylene group at C-11, and stereocontrolled 1,2-reduction of the alpha-hydroxy ketone functionality made available earlier.",10.1021/ja011285y,2001-08-22,0.5944659465204382
Synlett,"A Convenient Synthesis of Dialkyl [[2-(Bromomethyl)aziridin-1-yl]methyl]phosphonates, New Heterocyclic β-Azaphosphonates","All articles of this category Dialkyl [[2-(bromomethyl)aziridin-1-yl]methyl] phosphonates were prepared in good yield by a convenient procedure involving the reaction of 1,3,5-triallylhexahydro[1,3,5]triazine with dialkyl phosphites, subsequent bromination and final ring closure upon treatment with sodium borohydride in methanol. azaphosphonates - aziridines - aziridinylmethyl phosphonates",10.1055/s-1998-1597,1998-02-01,0.5944569066708735
Tetrahedron,First asymmetric synthesis of chiral analogues of the novel immunosuppressant FTY720,,10.1016/s0040-4039(02)01925-1,2002-11-01,0.5944545886000042
Organic Letters,A Cascade Phosphinoylation/Cyclization/Desulfonylation Process for the Synthesis of 3-Phosphinoylindoles,"3-Phosphinoylindole derivatives play important roles as pharmaceutical drugs and ligands. A new method for the synthesis of 3-phosphinoylindole derivatives has been achieved through silver-mediated cycloaddition between N-Ts-2-alkynylaniline derivatives and H-phosphine oxides. This transformation offers a straightforward route to the formation of the C-P bond, indole ring, and desulfonylation in one step.",10.1021/acs.orglett.6b00056,2016-02-29,0.5944524955650876
Angewandte Chemie International Edition,High‐Throughput Synthesis and Screening of a Cyanimide Library Identifies Selective Inhibitors of ISG15‐Specific Protease mUSP18,"High-throughput screening (HTS) of large compound collections is a critical early step in many drug discovery programs. Its success depends heavily on the quality of the compound libraries used, and as such, the development of targeted libraries has emerged to enhance the effectiveness of HTS efforts. However, the acquisition of such libraries remains costly and labor-intensive, often yielding compound quantities far exceeding required amounts. We present a high-throughput synthesis-to-screening method for the efficient in-plate generation and immediate HTS of a deubiquitinase (DUB)-focused compound library. Central to our approach is the Echo acoustic liquid handler, which transfers nanoliter volumes of DMSO-based solutions, facilitating miniaturized synthesis directly in 1536-well plates. We constructed a library of 7536 compounds featuring a DUB-privileged cyanimide warhead and screened against twelve ubiquitin(-like) proteases. This identified two structurally related molecules with selective inhibitory activity against the interferon-stimulated gene 15 (ISG15) protease mUSP18, which we further developed into a first-in-class mUSP18 inhibitor with 35 nM potency. This compound, BB07CA902, demonstrated exceptional specificity for mUSP18 across 41 DUBs and effectively increased ISGylation levels in cells by inhibiting mUSP18 activity. Our technology enables the efficient preparation of large DUB-targeted cyanimide-based libraries, which will accelerate future DUB inhibitor development.",10.1002/anie.202510941,2025-10-07,0.5944515063288972
Journal of Organic Chemistry,Synthesis of Naturally Occurring Pyridine Alkaloids via Palladium-Catalyzed Coupling/Migration Chemistry,"The palladium-catalyzed cross-coupling of 3-iodopyridine, long-chain terminal dienes, and benzylic amines or tosylamides provides a novel route to key intermediates for the synthesis of the naturally occurring, biologically active pyridine alkaloids theonelladins C and D, niphatesine C, and xestamine D. This process involves (1) oxidative addition of the heterocyclic iodide to Pd(0), (2) carbopalladation of the least hindered carbon-carbon double bond of the diene, (3) palladium migration, and (4) pi-allylpalladium displacement by the nitrogen nucleophile with simultaneous regeneration of the Pd catalyst. Subsequent hydrogenation and deprotection affords good yields of the natural products. The Pd-catalyzed coupling of 3-iodopyridine and 2-methyl-11-dodecen-1-ol provides a convenient synthesis of a long-chain aldehyde by an analogous palladium migration process, which is easily converted to the pyridine alkaloid ikimine A.",10.1021/jo026716p,2003-03-20,0.5944468007336902
Organic Letters,Pinacol Coupling Strategy for the Construction of the Bicyclo[6.4.1]tridecane Framework of Schiglautone A,"The synthesis of the tricyclic carbon framework of schiglautone A ( 1 ) is reported herein. The generation of the bicyclo[6.4.1]tridecane 19 was accomplished via a SmI 2 -mediated pinacol coupling of dialdehyde 18 . The side chain in 18 was introduced using a selective 1,4-addition. A further key step of the synthesis was the homologation of a Wieland–Miescher ketone derivative to establish the 7-membered ring.",10.1021/acs.orglett.7b00288,2017-03-16,0.5944461356783765
Journal of Organic Chemistry,"β-Selective <i>C</i>-Arylation of Diisobutylaluminum Hydride Modified 1,6-Anhydroglucose: Synthesis of Canagliflozin without Recourse to Conventional Protecting Groups","The β-selective phenylation of benzyl and boronate protected 1,6-anhydroglucose and the direct phenylation of unprotected 1,6-anhydroglucose (10), pretreated with i-Bu2AlH, i-Bu3Al, Et3Al, Me3Al, or n-octyl3Al, with triphenylalane or aryl(chloro)alanes is reported. The utility of the unprotected version of the method is demonstrated by the synthesis of the SGLT2 inhibitor, canagliflozin (1a), from commercially available 10 in one C-C bond-forming step. This approach circumvents the need for conventional protecting groups, and therefore no formal protection and deprotection steps are required.",10.1021/acs.joc.5b00601,2015-04-24,0.5944439932372676
Organic Letters,"Synthesis of 6,6′-Binaphthopyran-2-one Natural Products: Pigmentosin A, Talaroderxines A and B","Efficient and stereoselective syntheses of pigmentosin A, talaroderxine A, and its diastereomer talaroderxine B are reported. The binaphthyl ring system is assembled by vanadium-catalyzed phenolic coupling of tricyclic precursors. These key intermediates were prepared by Michael-Dieckmann annulation of a protected orsellinate ester, with the requisite pyranones accessed by a new variant of Ghosez's sulfone-epoxide annulation. Preliminary biological experiments are reported for pigmentosin.",10.1021/ol301743t,2012-08-13,0.5944437984935781
Tetrahedron,"Synthesis of 5-fluoro-1-β-D-ribofuranosylimidazole-4-carboxamide, an antiviral agent and inhibitor of polynucleotide biosynthesis",,10.1016/s0040-4039(00)91187-0,1975-01-01,0.5944432348213631
European Journal of Organic Chemistry,A Three‐Step Synthesis of the Guaianolide Ring System,"Abstract By using a gallium(III) triflate catalyzed intramolecular (4+3) cycloaddition, a few functionalized furan‐derived tricycles that share the common guaianolide sesquiterpene ring system were prepared in a stereoselective manner in only three steps from commercially available starting materials. A discussion of the formation of alternative products is included, with possible substrate requirements to achieve the key cycloaddition step in an efficient way.",10.1002/ejoc.201402170,2014-04-11,0.5944390680812585
Tetrahedron,"Synthetic studies on leinamycin. A synthesis of the 1-oxo-1,2-dithiolan-3-one moiety",,10.1016/0040-4039(92)89010-a,1992-09-01,0.5944336840738151
Tetrahedron,New strategy for the synthesis of key anthracycline precursors,,10.1016/s0040-4039(00)81379-9,1983-01-01,0.5944326676292317
Synlett,Novel Synthetic Route to Dihydropyrenes,"We developed a new and short synthetic route to 2,7-di-tert-butyl-trans-15,16-dimethyldihydropyrene (DHP) via tetra­hydroxy[2.2]metacyclophane in four reaction steps with a total yield of 37%. 2,7-Di-tert-butyl-trans-15,16-dimethyldihydro­pyrene functionalized by acetoxy groups at 4-, 5-, 9-, 10-positions was synthesized via 5,13-di-tert-butyl-8,16-dimethyl-1,2,9,10-tetra­hydroxy[2.2]MCP in five reaction steps with a yield of 24%, and its DHP structure was determined by ¹H NMR spectroscopy and X-ray crystal-structure analysis.",10.1055/s-0028-1087363,2008-11-27,0.5944323718322327
Tetrahedron,Enantioselective synthesis of valoneic acid derivative,,10.1016/j.tetlet.2007.11.154,2007-12-04,0.5944323073014594
Tetrahedron,Highly efficient lipase-catalyzed asymmetric synthesis of chiral glycerol derivatives leading to practical synthesis of s-propranolol,,10.1016/s0040-4039(00)80711-x,1988-01-01,0.594432269507414
Journal of Organic Chemistry,Total Synthesis of (±)-Oxacyclododecindione,"Racemic total synthesis of the natural product oxacyclododecindione, isolated in 2008 as the first member of the oxacyclododecindione family, is reported. Studies toward this molecule commenced with a biomimetic late-stage C-H oxidation starting from 14-deoxyoxacyclododecindione as a known precursor. This provided insights into the reactivity of the macrolactone class but did not permit the synthesis of the target natural product. Based on these results, a synthetic strategy through intramolecular Friedel-Crafts acylation combined with Barton decarboxylation to introduce the tertiary alcohol, a major challenge in previous synthetic efforts, was envisioned. This resulted in an 11-step racemic total synthesis of (±)-oxacyclododecindione, renowned for its potent anti-inflammatory and antifibrotic activities.",10.1021/acs.joc.4c00333,2024-04-10,0.5944322087078177
Tetrahedron,A new strategy for asymmetric synthesis of aminophosphonic acid derivatives: the first enantioselective catalytic reduction of C-phosphorylated imines,,10.1016/j.tetlet.2008.10.152,2008-11-08,0.5944163739325564
Synlett,"Total Synthesis of Prostaglandin F<sub>2α</sub> via Nickel-Promoted Stereoselective Cyclization of 1,3-Diene and Aldehyde","All articles of this category The total synthesis of prostaglandin F 2α (PGF 2α ) was accomplished via nickel-promoted cyclization of 1,3-diene and aldehyde in a chain in the presence of 1,3-cyclohexadiene (1,3-CHD). The cyclization of 16 prepared in an optically active form from chiral epoxy alcohol 10 stereoselectively gave the key intermediate 18 , which has both an α-chain and the four contiguous chiral carbon centers in PGF 2α , in a one-pot reaction. Intermediate 18 was successfully transformed into PGF 2α . prostaglandin - F 2α - nickel - cyclization - 1,3-diene - aldehyde",10.1055/s-1997-3268,1997-06-01,0.5944123308398852
Organic Letters,Enantioselective Total Synthesis of Isishippuric Acid B via Intramolecular Michael Reaction,"The first enantioselective total synthesis of isishippuric acid B bearing a novel 4,5-seco-6-norquadrane skeleton was accomplished from (R)-citronellal with use of a Diels-Alder cycloaddition and an intramolecular Michael addition as the ring-forming steps. Comparison of the optical rotation of the synthetic material with that of the natural product confirmed the absolute configuration of isishippuric acid B to be 1R, 2R, 8R, and 11R.",10.1021/ol070956f,2007-06-01,0.5944118174012583
Journal of the American Chemical Society,Total Synthesis of (+)-Lithospermic Acid by Asymmetric Intramolecular Alkylation via Catalytic C−H Bond Activation,"The total synthesis of (+)-lithospermic acid is described. The efficient synthesis features an asymmetric alkylation via C-H bond activation to assemble the dihydrobenzofuran core of the natural product. This was accomplished via a chiral imine-directed C-H bond functionalization and represents the first application of this C-H activation method to natural product synthesis. Furthermore, a challenging deprotection of a late-stage permethylated lithospermic acid was achieved.",10.1021/ja052680h,2005-09-08,0.5944105813833263
Organic Letters,"A Novel <i>C</i><sub>2</sub>-Symmetric 2,6-Diallylpiperidine Carboxylic Acid Methyl Ester as a Promising Chiral Building Block for Piperidine-Related Alkaloids","C(2)-symmetric 2,6-diallylpiperidine 1-carboxylic acid methyl ester (5) was examined via the double asymmetric allylboration of glutaraldehyde followed by aminocyclization and carbamation as a promising chiral building block for piperidine-related alkaloids, which were synthesized by the desymmetrization of 5 using intramolecular iodocarbamation as a key step. [reaction: see text]",10.1021/ol0265620,2002-09-05,0.594397238271549
Tetrahedron,"Biomimetic synthesis of the novel 1,4-dioxanyloxy fragment of silvestrol and episilvestrol",,10.1016/j.tetlet.2004.11.057,2004-12-15,0.5943961198001976
Tetrahedron,A novel synthesis of the C1–C17 fragment of carzinophilin,,10.1016/s0040-4039(00)78556-x,1994-12-01,0.5943961198001976
Green Chemistry,Silver-initiated radical ring expansion/fluorination of ethynyl cyclobutanols: efficient synthesis of monofluoroethenyl cyclopentanones,A stereoselective synthesis of β-halogenated 2-methylenecyclopentanones <italic>via</italic> silver-catalyzed formal ring expansion using water as the cosolvent is described.,10.1039/c6gc02656g,2016-01-01,0.5943959762208916
Tetrahedron,"Isolation, structure and synthesis of 4-hydroxyisoxazole (triumferol), a seed germination inhibitor from an african plant",,10.1016/s0040-4039(01)81929-8,1981-01-01,0.5943908977560105
Journal of Organic Chemistry,"Facile One-Pot Synthesis of 6-Monosubstituted and 6,12-Disubstituted 5,11-Dihydroindolo[3,2-<i>b</i>]carbazoles and Preparation of Various Functionalized Derivatives","A facile three-stage, one-pot approach for the synthesis of a variety of novel 6-monosubstituted and 6,12-disubstituted 5,11-dihydroindolo[3,2-b]carbazoles, in moderate to good yields (20-50%), has been developed, based on the condensation of an indole and an aldehyde with a catalytic amount of iodine, followed by an acid-catalyzed intramolecular cyclization with an ortho ester. The parent indolo[3,2-b]carbazoles (ICZs) could be converted to various functional derivatives. Both N-alkylation and N-arylation were successfully accomplished, and azo-coupling, formylation, as well as bromination were performed in a regioselective way leading to the formation of novel functional 6,12-disubstituted indolo[3,2-b]carbazoles. Starting from a monoformylated indolocarbazole, novel benzimidazolyl-substituted derivatives were synthesized, while Suzuki cross-couplings on a monobrominated building block afforded a novel pathway toward functionally arylated ICZs.",10.1021/jo0711337,2007-08-15,0.5943889603530637
Tetrahedron,"Synthesis of chiral 2,3-disubstituted 1,4-diazabicyclo [2.2.2] octane. New ligand for the osmium-catalyzed asymmetric dihydroxylation of olefins",,10.1016/s0040-4039(00)92331-1,1992-01-01,0.5943818524481257
Synlett,"Efficient One-Pot Synthesis of 6-Arylpyrrolo[3,2-d]pyrimidines from 6-Arylethynyl-5-nitropyrimidines","A highly concise one-pot synthesis of 6-arylpyrrolo[3,2-d]pyrimidines via conjugative addition reaction of secondary amines to 6-arylethynyl-5-nitropyrimidines and subsequent reduction is described.",10.1055/s-0029-1219544,2010-02-23,0.5943787474395165
Synlett,"Enantioselective Synthesis of Bicyclo[4.4.1]undecane-2,7-dione via Samarium(II)-Mediated Fragmentation of a Cyclopropane Precursor","An efficient six-step synthesis of bicyclo[4.4.1]undecane-2,7-dione was elaborated. Key steps include an enantioselective oxazaborolidine-catalyzed borane reduction (CBS reduction) of 2,3,4,6,7,8-hexahydronaphthalene-1,5-dione to the corresponding diol, and a subsequent (syn-diastereoselective) cyclopropanation. Oxidation then gives tricyclo[4.4.1.01,6]undecane-2,7-dione (>99% ee) which on treatment with two equivalents of samarium(II) iodide undergoes cleavage of the central cyclopropane bond to yield the target compound without any loss of stereochemical information.",10.1055/s-2006-941599,2006-06-01,0.5943767483736849
Journal of Organic Chemistry,Syntheses and Cytotoxicity of (<i>R</i>)- and (<i>S</i>)-7-Methoxycryptopleurine,"Two efficient protocols are described for the transformation of a key chiral homoallyllic sulfinamine intermediate in four steps into enantioenriched 7-methoxycryptopleurine. While one of the protocols relied on a rhodium catalyzed linear hydroformylation process, the alternative approach was based on a ring-closing metathesis from the corresponding N-allyl-sulfinamine. The cytotoxic evaluation of both enantiomers of the target compound demonstrated that the (R)-compound is much more potent than its antipode against the four cancer cell lines examined.",10.1021/jo502660r,2015-01-07,0.594373902748158
Organic Letters,Stereoselective Convergent Synthesis of a <i>trans</i>-Fused Polycyclic Ether Ring System Including a 4-Hydroxy-5-methyl-tetrahydropyran Ring,"[reaction: see text] Stereoselective convergent synthesis of a trans-fused 6-6-6-6-membered tetracyclic ether ring system including 4alpha- or 4beta-hydroxy-5-methyl-tetrahydropyran was achieved. The key reactions involve the acetylide-aldehyde coupling of two tetrahydropyrans, intramolecular hetero-Michael cyclization of enone, stereoselective reduction of enone, hydroboration, intramolecular acetalization, and stereoselective reduction of the acetal with Et(3)SiH-TMSOTf.",10.1021/ol026261q,2002-07-10,0.5943727881301125
Journal of the American Chemical Society,Catalysis-Based Total Syntheses of Pateamine A and DMDA-Pat A,"The marine natural product pateamine A (1) and its somewhat simplified designer analogue DMDA-Pat A (2) (DMDA = desmethyl-desamino) are potently cytotoxic compounds; most notably, 2 had previously been found to exhibit a promising differential in vivo activity in xenograft melanoma models, even though the ubiquitous eukaryotic initiation factor 4A (eIF4A) constitutes its primary biological target. In addition, 1 had also been identified as a possible lead in the quest for medication against cachexia, an often lethal muscle wasting syndrome affecting many immunocompromised or cancer patients. The short supply of these macrodiolides, however, rendered a more detailed biological assessment difficult. Therefore, a new synthetic approach to 1 and 2 has been devised, which centers on an unorthodox strategy for the formation of the highly isomerization-prone but essential Z, E-configured dienoate substructure embedded into the macrocyclic core. This motif was encoded in the form of a 2-pyrone ring and unveiled only immediately before macrocyclization by an unconventional iron-catalyzed ring opening/cross-coupling reaction, in which the enol ester entity of the pyrone gains the role of a leaving group. Since the required precursor was readily available by gold catalysis, this strategy rendered the overall sequence short, robust, and scalable. A surprisingly easy protecting group management together with a much improved end game for the formation of the trienyl side chain via a modern Stille coupling protocol also helped to make the chosen route practical. Change of a single building block allowed the synthesis to be redirected from the natural lead compound 1 toward its almost equipotent analogue 2. Isolation and reactivity profiling of pyrone tricarbonyliron complexes provide mechanistic information as well as insights into the likely origins of the observed chemoselectivity.",10.1021/jacs.8b05094,2018-07-28,0.5943573511327503
Organic Letters,Bioinspired Total Synthesis of Penisuloxazin A,"The first total synthesis of epidithiodiketopiperazine (ETP) alkaloid penisuloxazin A is described. The key steps of the synthesis involve the La(III)-mediated aldol reaction to construct a benzylic alcohol, which serves as the precursor for rearrangement. Subsequently, a bioinspired Lewis acid-catalyzed rearrangement reaction facilitates sulfur migration, forming the 6/5/6 spiro-benzofuran ring system with an irregular α-β' disulfide skeleton. This synthesis produces penisuloxazin A in 14 steps from inexpensive, available materials. The method could be a general strategy for making irregular α-β' disulfide bridge ETPs, especially those with hydroxamic acids.",10.1021/acs.orglett.5c01488,2025-05-30,0.5943562753986044
Journal of the American Chemical Society,"Efficient, Chemoenzymatic Process for Manufacture of the Boceprevir Bicyclic [3.1.0]Proline Intermediate Based on Amine Oxidase-Catalyzed Desymmetrization","The key structural feature in Boceprevir, Merck's new drug treatment for hepatitis C, is the bicyclic [3.1.0]proline moiety ""P2"". During the discovery and development stages, the P2 fragment was produced by a classical resolution approach. As the drug candidate advanced through clinical trials and approached regulatory approval and commercialization, Codexis and Schering-Plough (now Merck) jointly developed a chemoenzymatic asymmetric synthesis of P2 where the net reaction was an oxidative Strecker reaction. The key part of this reaction sequence is an enzymatic oxidative desymmetrization of the prochiral amine substrate.",10.1021/ja3010495,2012-03-12,0.5943535188889989
Synlett,Facile Synthesis of N-Substituted 4-Amino-6-methyl Resorcinols from Polysubstituted Cyclohexanone,"A novel synthesis of N-substituted 4-​amino-​6-​methyl resorcinols from polysubstituted cyclohexanone was developed. The reaction was performed in an easy ‘one-pot’, tandem manner with well-tolerated substituent on the nitrogen to give the desired compound in good to excellent yield. This highly efficient method will find broad application in the synthesis of some natural products and bioactive interesting compounds.",10.1055/s-0036-1590817,2017-07-11,0.5943520579061422
Angewandte Chemie International Edition,"Organocatalytic Asymmetric Hydrophosphination of α,β‐Unsaturated Aldehydes","Getting round the (periodic) table: A highly chemo- and enantioselective conjugate addition of diphenylphosphine to α,β-unsaturated aldehydes in the presence of a chiral secondary amine C provides a direct route to chiral β-phosphino aldehyde intermediates (see scheme, TMS=trimethylsilyl). The synthetic utility of the strategy was exemplified in a rapid one-pot (two-step) synthesis of highly enantioenriched 3-aminophosphines.",10.1002/anie.200700754,2007-05-04,0.5943458450198625
Tetrahedron,Stereoselective palladium catalyzed cyclization on carbohydrate templates- a route to chiral cyclopentanes and some heterocyclic analogs,,10.1016/s0040-4039(00)71264-0,1991-05-01,0.5943431672257214
Organic Letters,Expanding the Scope of a One-Pot Double Displacement Protocol to Access the All-Rare-Sugar-Containing Trisaccharide Unit of <i>Pseudomonas stutzeri</i> OX1,"Herein, we have explored a one-pot bis-triflation and regioselective displacement protocol with d -fucose 2,4-diol to access various rare 6-deoxy amino d -sugars. This strategy enabled the first total synthesis of the trisaccharide unit of Pseudomonas stutzeri OX1 strain containing d -perosamine and d -tomosamine. Installation of a 1,2- cis linkage and late-stage N -formylation are the key challenges in the total synthesis, which was accomplished via the longest linear sequence of 21 steps with 1.2% overall yield.",10.1021/acs.orglett.4c03788,2024-11-12,0.5943396172156797
Journal of the American Chemical Society,A Concise Approach to Paxilline Indole Diterpenes,"A synthetic approach to paxilline indole diterpenes is described. The route to the pentacyclic core relies on a new regioselective alkenylation of ketones and a tandem radical addition-aldol reaction sequence to access vicinal quaternary stereocenters. Emindole SB, the simplest member of the family, is synthesized in 11 steps from commercially available material to demonstrate the application of this approach.",10.1021/jacs.5b11129,2015-11-23,0.594334577913595
Angewandte Chemie International Edition,A Concise Total Synthesis of (+)‐Neopeltolide,"Short and sweet: The highly potent antiproliferative marine macrolide (+)-neopeltolide has been synthesized based on the strategic application of olefin metathesis reactions. The total synthesis proceeded in only 13 steps from commercially available starting materials, and represents the shortest synthesis of (+)-neopeltolide reported to date.",10.1002/anie.201000624,2010-03-22,0.5943337769454102
Synlett,3-Methoxy-1-phenylthio-1-propene as d<sup>1</sup>/ d<sup>3</sup>Synthon: Application for an Asymmetric Synthesis of (<i>S</i>)-(+)-<i>Parasorbic Acid</i>,"(opens in new window) Buy Article (opens in new window) Permissions and Reprints (opens in new window) All articles of this category (opens in new window) Regioselective ring-opening of oxiranes with the sulfurstabilized anion 1 of 3-methoxy-1-phenylthio-1-propene and acidcatalyzed cyclization of the resulting bishomoallyl alcohols 2a-f leading to the tetrahydropyrans 3a-f are key-steps in the synthesis of α,β-unsaturated δ-lactones. An enantioselective synthesis of ( S )-(+)- parasorbic acid ( 14 ) has been developed starting from ( S )-(-)-epoxypropane ( 9 ).",10.1055/s-1994-22938,1994-01-01,0.5943263328935697
Tetrahedron,Stannylfuranones in synthesis: Highly enantioselective preparation of (+)-hamabiwalactone B,,10.1016/s0040-4039(98)01946-7,1998-11-01,0.5943232536828447
Synlett,Simple Preparation of an Optically Pure Daunomycinone A-Ring Precursor from (-)-Quinic Acid,"All articles of this category A new, optically pure synthon for the A-ring of daunomycinone has been synthesized in six steps and an overall yield of 17% starting from (-)-quinic acid.",10.1055/s-1990-21036,1990-01-01,0.594321015624501
Synthesis,A New Synthesis of 2-Aryl-3-chloro-2<i>H</i>-indazoles,,10.1055/s-1979-28663,1979-01-01,0.5943191247413947
Synthesis,"A New Synthesis of Progesterone from 17-[Isocyano(tosyl)methylene]-3-methoxyandrosta-3,5-diene","All articles of this category Progesterone (4) is synthesized in 93% overall yield in three steps from 17-[( E )-isocyano(tosyl)methylene]-3-methoxyandrosta-3,5-diene (1) .",10.1055/s-1991-26509,1991-01-01,0.5943174841324683
Tetrahedron,Indole: A novel leaving group in the synthesis of oligonucleoside methylphosphonates,,10.1016/s0040-4039(97)00333-x,1997-03-01,0.5943135567771624
Organic Letters,Synthesis of the Bicyclic Welwitindolinone Core via an Alkylation/Cyclization Cascade Reaction,Synthesis of an advanced welwitindolinone intermediate via an alkylation/cyclization reaction is reported. The key step involves a one pot Lewis acid-mediated alkylation of a silylketene aminal with a furan alcohol followed by an intramolecular cyclization. The reaction is stereoselective and takes place at low temperature. The cycloadduct was highly functionalized and contains the welwitindolinone core structure.,10.1021/ol902173g,2009-10-27,0.5943018062408686
European Journal of Organic Chemistry,A Convergent Synthesis of Gonytolide C Using an Intramolecular Oxa‐Michael Addition,"Abstract A full account of the evolution of a convergent total synthesis of gonytolide C is reported. The assembly of the natural product core relies on a Horner–Wadsworth–Emmons (HWE) olefination followed by an intramolecular oxa‐Michael addition. Robust and efficient preparations of both HWE coupling partners were established. The synthesis enabled further investigation of an asymmetric oxa‐Michael cyclisation to prepare gonytolide C, demonstrating the utility of this strategy for synthesis of 2,2‐disubstituted chromanones.",10.1002/ejoc.201501402,2016-01-27,0.5942997982724764
Angewandte Chemie International Edition,Total Synthesis of (±)‐Strictamine,"The total synthesis of strictamine has been achieved in nine steps from a known enol triflate. Characteristic features of our approach included: a) creation of a C7 all-carbon quaternary stereocenter at an early synthetic stage; b) use of an N,N-dimethyl tertiary amine as a surrogate of the primary amine for the rapid build-up of a functionalized 2-azabicyclo[3,3,1]nonan-9-one skeleton (achieved by using a reaction sequence of α-bromination of the ketone, followed by a stereoconvergent intramolecular nucleophilic substitution reaction); and c) a late-stage construction of the indolenine unit.",10.1002/anie.201511638,2016-02-04,0.5942951162100234
Organic Letters,Synthesis of Thromboxane B<sub>2</sub>via Ketalization/Ring-Closing Metathesis,"Total synthesis of thromboxane B2 using intermolecular ketalization followed by ring-closing metathesis is reported. Other key steps include a Sharpless asymmetric epoxidation to form an oxirane on the endo face of the bicyclic acetal, epoxide opening using lithioacetonitrile, an allylic alcohol 1,3-transposition, and Mitsunobu lactonization.",10.1021/ol7021214,2007-11-30,0.5942930268759922
Organic Process Research & Development,Commercially Viable Synthesis of Medetomidine Using a Classical Approach to the Imidazole Ring Formation,"A commercially viable and efficient method for the synthesis of medetomidine hydrochloride ( 1 ) was developed combining two reliable synthetic approaches: the modern method for C–C bond formation through the sp 2 –sp 3 Kumada cross-coupling and the classical method for the imidazole ring formation based on the Weidenhagen reaction. The latter was earlier limited by the high toxicity of hydrogen sulfide used to recover imidazoles from the copper complexes and difficulties in working up the reaction mixture. We achieved a remarkable advance in the Weidenhagen reaction through the use of nonhazardous complexons providing less than a 10 ppm residual level of metals in the final product. In the developed method, 3-(2,3-dimethylphenyl)butan-2-one ( 7 ) is synthesized in a one-step and one-pot manner by the cross-coupling of 2-(1-bromoethyl)-2-methyl-1,3-dioxolane ( 14 ) and 2,3-dimethylphenyl magnesium bromide ( 10 ), followed by one-pot deprotection of the resulting ethylene ketal 8, and several intermediates at the next steps can be used without additional purification; these benefits enable medetomidine hydrochloride ( 1 ) to potentially be produced on a multikilogram scale.",10.1021/acs.oprd.2c00273,2022-11-07,0.5942891800363782
Organic Letters,A Racemic Synthesis of an AB-Ring System of Hexacyclinic Acid,"[structure: see text] An AB-ring system of the polyketide natural product hexacyclinic acid has been synthesized in racemic form. The key steps were an intramolecular Diels-Alder cyclization of an ester tethered 1,3-nonadiene-8-yne, which generated the B-ring, and a samarium diiodide mediated reductive annulation, which was used to form the A-ring.",10.1021/ol051633r,2005-08-23,0.5942870075616011
Organic Process Research & Development,"Synthesis of a Spiro[cyclohex-1,1‘-isobenzofuranyl] Dopamine Receptor Antagonist","Two syntheses of the novel CNS agent, 2-fluoro-4-( trans )-(4-(3‘H-spiro[cyclohex-1,1‘-isobenzofuran]-4-yl)-piperazin-1-yl)-benzonitrile, 1, are presented. The first relied on a reductive alkylation with low regioselectivity (1:1) but was sufficient for the preparation of kilogram quantities. The second used a selective ketone reduction of 3‘H-spiro[cyclohexane-1,1‘-isobenzofuran]-4-one, 8, with sodium borohydride to provide the cis -alcohol, 3‘H-spiro[cyclohexane-1,1‘-isobenzofuran]-( cis )-4-ol, 11 . A simple process for the conversion of 11 to 1 is described. Regioselective reactions with 2,4-difluorobenzonitrile under mild conditions are described.",10.1021/op990191u,1999-10-27,0.5942869780134571
Journal of the American Chemical Society,Enantio- and Diastereoselective Synthesis of <i>N</i>-Acetyl Dihydrotetrafibricin Methyl Ester,"A highly diastereoselective synthesis of N-acetyl dihydrotetrafibricin methyl ester (34) is described. The synthesis features three enantioselective double allylboration reactions and an intramolecular hydrosilylation/Fleming-Tamao oxidation sequence to establish seven of the hydroxy-bearing stereocenters of 34. Especially noteworthy is the fragment-assembly double allyboration reaction of 2 and 7 using reagent 3, which provides the advanced intermediate 6 with >20:1 diastereoselectivity.",10.1021/ja401918r,2013-03-26,0.5942816608556297
Synthesis,"Application of Phenolate Ion Mediated Intramolecular Epoxide Ring Opening in the Enantioselective Synthesis of Functionalized 2,3-Dihydrobenzofurans and 1-Benzopyrans¹","The enantioselective synthesis of 2-isopropenyl-2,3-dihydrobenzofurans, 4-(2,3-dihydrobenzofuran-2-yl)-2-methylbut-3-en-2-ols, 2-hydroxymethyl chromans, and 4-chroman-2-yl-2-methylbut-3-en-2-ols has been achieved using Sharpless asymmetric epoxidation-derived enantiomerically enriched epoxy alcohols as chiral building blocks. A phenolate ion mediated intramolecular epoxide ring-opening reaction was the key step for every cyclization reaction.",10.1055/s-0028-1088077,2009-04-27,0.5942795752267522
Organic Letters,A Formal Synthesis of Swainsonine by Gold-Catalyzed Allene Cyclization,A formal synthesis of swainsonine has been achieved using a highly efficient and diastereoselective gold(III)-catalyzed allene cyclization.,10.1021/ol901094h,2009-08-13,0.5942782330289953
European Journal of Organic Chemistry,A Repetitive Approach to the Synthesis of Medium and Large Ring Compounds with a Ring-Opening/Ring-Closure Cascade Reaction of Siloxycyclopropane Derivatives as Crucial Step,"Starting from siloxycyclopropyl-substituted dimethyl malonates 1 and 2 a chain elongation was performed to give new malonates 8, 9, 10, and 18 in reasonable overall yield. Further elongation by five carbon atoms transforms 10 into 15. Precursor 21 was prepared by alkylation of cyclopropanecarboxylate 20 with dibromide 17 and subsequent treatment with sodium dimethyl malonate. Compounds 8, 9, 10, 15, 18, and 21 were subjected to cesium fluoride under high dilution which induced a ring-opening/ring-closure cascade reaction giving cyclopentadecanone derivatives 11, 12, 13, cycloeicosanone derivative 16, cyclotetradecanone derivative 19 and cyclononane derivative 22 (together with 23). The efficiency of this reaction including an intramolecular Michael addition is discussed. The sequence allows efficient synthesis of medium and large carbocycles by a highly flexible building block system involving in principle unlimited repetition of construction steps. An X-ray analysis of 19 reveals its crown-like conformation which is slightly distorted to a more planar skeleton compared with a ten-membered ring analog 24.",10.1002/(sici)1099-0690(199811)1998:11<2541::aid-ejoc2541>3.3.co;2-r,1998-11-01,0.5942776799501236
European Journal of Organic Chemistry,A Repetitive Approach to the Synthesis of Medium and Large Ring Compounds with a Ring‐Opening/Ring‐Closure Cascade Reaction of Siloxycyclopropane Derivatives as Crucial Step,"Starting from siloxycyclopropyl-substituted dimethyl malonates 1 and 2 a chain elongation was performed to give new malonates 8, 9, 10, and 18 in reasonable overall yield. Further elongation by five carbon atoms transforms 10 into 15. Precursor 21 was prepared by alkylation of cyclopropanecarboxylate 20 with dibromide 17 and subsequent treatment with sodium dimethyl malonate. Compounds 8, 9, 10, 15, 18, and 21 were subjected to cesium fluoride under high dilution which induced a ring-opening/ring-closure cascade reaction giving cyclopentadecanone derivatives 11, 12, 13, cycloeicosanone derivative 16, cyclotetradecanone derivative 19 and cyclononane derivative 22 (together with 23). The efficiency of this reaction including an intramolecular Michael addition is discussed. The sequence allows efficient synthesis of medium and large carbocycles by a highly flexible building block system involving in principle unlimited repetition of construction steps. An X-ray analysis of 19 reveals its crown-like conformation which is slightly distorted to a more planar skeleton compared with a ten-membered ring analog 24.",10.1002/(sici)1099-0690(199811)1998:11<2541::aid-ejoc2541>3.0.co;2-#,1998-11-01,0.5942776799501236
Organic Letters,"Total Syntheses of (−)-Hanishin, (−)-Longmide B, and (−)-Longmide B Methyl Ester <i>via</i> a Novel Preparation of <i>N</i>-Substituted Pyrrole-2-Carboxylates","A novel preparation of N-substituted pyrrole-2-carboxylates has been developed based upon 1,3-dipolar cycloaddition and a conventional hydrogenolysis. By using this method as the key step, total syntheses of natural alkaloids (-)-hanishin, (-)-longamide [corrected] B, and (-)-longamide [corrected] B methyl ester were accomplished in the highest overall yields, respectively.",10.1021/ol203433c,2012-02-08,0.5942719523337007
Synthesis,"Stereoselective Synthesis of Unnatural β-Amino Acids from Nitroethane via 5,6-Dihydro-4H-1,2-oxazin-3-ylacetates","The reduction of easily available methyl 5,6-dihydro-4H-1,2-oxazin-3-ylacetates provides an efficient route to different diastereomerically pure unnatural β-amino acids. A two-step protocol including reduction of the C=N bond of the initial oxazine with sodium cyanoborohydride during the first step and hydrogenation of the N-O bond during the second step produced the target β-amino acid esters with higher stereoselectivity than obtained with conventional catalytic hydrogenation.",10.1055/s-0029-1216872,2009-06-26,0.5942708573764713
Organic Process Research & Development,Process Development of a Platelet Aggregation Inhibitor,"A practical and efficient method for N -amination of piperazine via a nitrosoamine, suitable for a large scale synthesis, is described. This method involved the temporary transformation of an in situ prepared aminopiperazine to a hydrazone, allowing efficient separation of zinc salt byproducts from the system. Acylation and deprotection with hydroxylamine directly afforded FR062732 in satisfactory quality for pharmacological evaluation. These methods solved the operational problems usually inherent in zinc reduction of nitrosoamines.",10.1021/op980050c,1998-09-12,0.5942544648362275
Tetrahedron,Intramolecular palladium-catalyzed cyclization of methyl 1-(2-bromobenzyl)indole-2-carboxylates: Synthesis of pratosine and hippadine,,10.1016/s0040-4039(99)00687-5,1999-06-01,0.5942534007648637
Journal of Organic Chemistry,Hydrogen atom abstraction reactions in organic synthesis. A formal total synthesis of racemic podophyllotoxin,"The key step in a synthesis of 1 was a tandem photoenolization/Diels-Alder reaction to produce 11. Hydrolysis of the acetal and ester followed by oxidation afforded 15, an advanced intermediate in the Meyers synthesis of 1.",10.1021/jo00036a030,1992-05-01,0.5942347194706583
Journal of the American Chemical Society,"A Concise, Enantioselective Approach for the Synthesis of Yohimbine Alkaloids","We report a concise, enantioselective synthesis of the yohimbine alkaloids (−)-rauwolscine and (−)-alloyohimbane. The key transformation involves a highly enantio- and diastereoselective NHC-catalyzed dimerization and an amidation/ N -acyliminium ion cyclization sequence to furnish four of the five requisite rings and three of the five stereocenters in two operations. This route also provides efficient access to all four diastereomeric arrangements of the core stereotriad of the yohimbine alkaloids from a common intermediate. This platform approach in combination with the ability to access both enantiomers from the carbene-catalyzed reaction is a powerful strategy that can produce a wide range of complex alkaloids and related structures for future biomedical investigations.",10.1021/jacs.9b12319,2020-01-17,0.5942325164932588
Journal of the American Chemical Society,"New Chemical Synthesis of the Promising Cancer Chemotherapeutic Agent 12,13-Desoxyepothilone B: Discovery of a Surprising Long-Range Effect on the Diastereoselectivity of an Aldol Condensation","The epothilones are naturally occurring cytotoxic molecules that possess the remarkable ability to arrest cell division through the stabilization of microtubule assemblies. Our in vivo studies with 12,13-desoxyepothilone B (dEpoB), have established that the desoxy compound is well tolerated and virtually curative against a variety of sensitive and resistant xenograft tumors in animal models. In light of these discoveries, we sought a chemical synthesis of dEpoB that would be able to support a serious and substantial discovery research program directed toward the clinical development of this molecule. The overall strategy for this endeavor assumed the ability to synthesize dEpoB from three constructs which include an achiral β,δ-diketo ester construct A, an ( S )-2-methylpentenal moiety B, and the thiazoyl-containing vinyl iodide moiety C . We envisioned that a diastereoselective aldol condensation between an achiral C5−C6 ( Z )-metalloenolate derived from construct A and an ( S )-2-methylalkanal fragment, B, would generate the desired C6−C7 bond. Second, a B -alkyl Suzuki coupling between the vinyl iodide construct C and an alkyl borane would form the C11−C12 bond. Finally, a late-stage reduction of the C3 ketone to the requisite C3 alcohol with high asymmetric induction would permit us to introduce the β,δ-diketo ester fragment A, into the synthesis as a readily accessible achiral building block. The governing concepts for our new synthesis are described herein.",10.1021/ja991189l,1999-07-20,0.5942250712396414
Green Chemistry,Biocatalyzed route for the preparation of surface-deacetylated chitin nanofibers,Schematic diagram of a novel approach to prepare chitin nanofibers <italic>via</italic> CDA.,10.1039/c9gc00857h,2019-01-01,0.5942244037830037
Tetrahedron,Novel asymmetric synthesis of penaresidin B as a potent actomyosin ATPase activator,,10.1016/s0040-4039(97)00603-5,1997-05-01,0.5942241651525113
Synthesis,"Two-Step Synthesis of (<i>Z</i>)-2-[2-Oxo-2,3-dihydropyrido[2,3-<i>d</i>]pyrimidin-4(1<i>H</i>)-ylidene]acetamide Derivatives from 2-Chloro-6-methylpyridine-3-carbonitrile","(Z)-2-[1-Aryl-7-methyl-2-oxo-2,3-dihydropyrido[2,3-d]pyrimidin-4(1H)-ylidene]acetamides were prepared using a two-step sequence. The first step was the addition of magnesium enol­ates of tertiary acetamides to 2-chloro-6-methylpyridine-3-carbo­nitrile to give vinylogous urea derivatives, (Z)-3-amino-3-(2-chloro-6-methylpyridin-3-yl)propenamides. In the second step, these were reacted with aryl isocyanates in the presence of sodium hydride to give the corresponding pyrido[2,3-d]pyrimidin-2(1H)-one derivatives.",10.1055/s-2006-950380,2006-12-20,0.5942223572301395
Tetrahedron,"Highly stereoselective asymmetric aldol routes to tert-butyl-2-(3,5-difluorophenyl)-1-oxiran-2-yl)ethyl)carbamates: Building blocks for novel protease inhibitors",,10.1016/j.tetlet.2017.09.025,2017-09-14,0.5942212039927013
Journal of Organic Chemistry,Chemoselective Protection of Glutathione in the Preparation of Bioconjugates: The Case of Trypanothione Disulfide,"A novel synthetic route to the chemoselectively protected N,S-ditritylglutathione monomethyl ester is described involving the chemical modification of the commercially available glutathione (GSH). The synthetic value of this building block in the facile preparation of GSH bioconjugates in a satisfying overall yield was exemplified by the case of trypanothione disulfide (TS2), a GSH-spermidine bioconjugate, involved in the antioxidative stress protection system of parasitic protozoa, such as trypanosoma and leishmania parasites.",10.1021/acs.joc.6b00300,2016-05-03,0.5942197514719427
Journal of the American Chemical Society,"Inhibition of IspH, a [4Fe–4S]<sup>2+</sup> Enzyme Involved in the Biosynthesis of Isoprenoids via the Methylerythritol Phosphate Pathway","The MEP pathway, which is absent in animals but present in most pathogenic bacteria, in the parasite responsible for malaria and in plant plastids, is a target for the development of antimicrobial drugs. IspH, an oxygen-sensitive [4Fe-4S] enzyme, catalyzes the last step of this pathway and converts (E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate (HMBPP) into the two isoprenoid precursors: isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). A crucial step in the mechanism of this enzyme is the binding of the C4 hydroxyl of HMBPP to the unique fourth iron site in the [4Fe-4S](2+) moiety. Here, we report the synthesis and the kinetic investigations of two new extremely potent inhibitors of E. coli IspH where the OH group of HMBPP is replaced by an amino and a thiol group. (E)-4-Mercapto-3-methylbut-2-en-1-yl diphosphate is a reversible tight-binding inhibitor of IspH with K(i) = 20 ± 2 nM. A detailed kinetic analysis revealed that (E)-4-amino-3-methylbut-2-en-1-yl diphosphate is a reversible slow-binding inhibitor of IspH with K(i) = 54 ± 19 nM. The slow binding behavior of this inhibitor is best described by a one-step mechanism with the slow step consisting of the formation of the enzyme-inhibitor (EI) complex.",10.1021/ja309557s,2013-01-14,0.5942153435129983
Tetrahedron,A de novo synthesis of ethyl 2-deoxy-l-ribosides,,10.1016/s0040-4039(98)00852-1,1998-06-01,0.5942127495339232
Journal of Organic Chemistry,Synthesis of (+)-Coronafacic Acid,An enantioselective synthesis of (+)-coronafacic acid has been achieved. Rhodium-catalyzed cyclization of an alpha-diazoester provided the intermediate cyclopentanone in high enantiomeric purity. Subsequent Fe-mediated cyclocarbonylation of a derived alkenyl cyclopropane gave a bicyclic enone that then was hydrogenated and carried on to the natural product.,10.1021/jo802493k,2009-02-20,0.5942018376711493
European Journal of Organic Chemistry,Synthesis of Silodosin by Copper‐Catalysed C–C Arylation,"Abstract The synthesis of silodosin, an antidysuria drug, has been accomplished starting from commercially available indoline. The synthetic strategy is based on Cu I ‐catalysed C–C arylation, regioselective cyanation, and diastereoselective reductive amination. The enantiopure compound was obtained by selective crystallisation of a diasteroisomeric mixture.",10.1002/ejoc.201500753,2015-08-07,0.5942007356945062
Organic Letters,"A Novel Highly Stereoselective Synthesis of 2,3-Disubstituted <i>3H</i>-Quinazoline-4-one Derivatives",[structure: see text]. An efficient three-step synthesis of chiral 3H-quinazoline-4-one derivatives from commercial materials is disclosed. The Mumm reaction of imidoyl chloride with alpha-amino acids followed by reductive cyclization affords enantiomerically pure (ee >93%) quinazoline-4-ones in good overall yield. A comparison with existing approaches indicates that this method is superior for hindered substrates.,10.1021/ol070276c,2007-03-01,0.5941998147813453
Tetrahedron,A convenient synthesis of phebalosin: first total synthesis of murraxocin,,10.1016/j.tetlet.2015.05.106,2015-06-05,0.5941845767367826
Tetrahedron,Ethylbenzene Hydroperoxide: An efficient oxidizing agent for diastereoselective synthesis of Spiroepoxy oxindoles,,10.1016/j.tetlet.2022.154126,2022-09-05,0.5941814766196037
Synthesis,A Convenient Route to Dethio-6-aminopenicillanic Acid,,10.1055/s-1977-24460,1977-01-01,0.5941757328025388
Tetrahedron,Synthesis of the C-ring fragment of cobyric acid,,10.1016/s0040-4039(99)01134-x,1999-08-01,0.5941755144080569
European Journal of Organic Chemistry,Total Synthesis of Estradiol Methyl Ether and Its Five‐Pot Synthesis with an Organocatalyst,"Enantioselective total synthesis of estradiol methyl ether has been accomplished in a highly diastereo‐ and enantioselective manner. The key reaction is diphenylprolinol silyl ether mediated domino Michael/aldol reaction to afford bicyclo[4.3.0]nonane derivatives with A, C, and D rings of the steroids as a single isomer with excellent enantioselectivity. Each reaction was optimized, and the total synthesis could be accomplished in 12 pots with 10 purifications using silica gel, resulting in an overall yield of 6.8 %. The reaction sequence and reaction conditions were then optimized in terms of pot economy, whereupon estradiol methyl ether could be synthesized using five reaction vessels with four purifications in an overall yield of 15 %. Notably, six reactions, namely, oxidation, hydrogenation, formation of acid chloride, Friedel–Crafts reaction, deprotection, and reduction could be carried out in the last one‐pot sequence.",10.1002/ejoc.201800910,2018-07-17,0.5941675496688941
Journal of Organic Chemistry,"Peloruside B, A Potent Antitumor Macrolide from the New Zealand Marine Sponge Mycale hentscheli: Isolation, Structure, Total Synthesis, and Bioactivity","Peloruside B (2), a natural congener of peloruside A (1), was isolated in sub-milligram quantities from the New Zealand marine sponge Mycale hentscheli. Peloruside B promotes microtubule polymerization and arrests cells in the G(2)/M phase of mitosis similar to paclitaxel, and its bioactivity was comparable to that of peloruside A. NMR-directed isolation, structure elucidation, structure confirmation by total synthesis, and bioactivity of peloruside B are described in this article. The synthesis features Sharpless dihydroxylation, Brown's asymmetric allylboration reaction, reductive aldol coupling, Yamaguchi macrolactonization, and selective methylation.",10.1021/jo9021265,2009-12-03,0.594160380669199
Journal of the American Chemical Society,Enantioselective Divergent Syntheses of Diterpenoid Pyrones,"Capitalizing a synergy between late-stage C(sp 3 )–H alkynylation and a series of transition metal-catalyzed alkyne functionalization reactions, we reported herein enantioselective divergent synthesis of 10 diterpenoid pyrones within 14–16 steps starting from chiral pool enoxolone, including the first enantioselective synthesis of higginsianins A, B, D, E, and metarhizin C. Our synthesis also highlights an unprecedented biomimetic oxidative rearrangement of α-pyrone into 3(2H)-furanone, as well as applications of Echavarren C(sp 3 )–H alkynylation reaction and Toste chiral counterion-mediated Au-catalyzed intramolecular allene hydroalkoxylation in natural product synthesis.",10.1021/jacs.4c01788,2024-03-18,0.5941572088601345
Tetrahedron,"Efficient synthesis of chiral C2-symmetric diamines via allylboration of bis-N,N′-metallodiimines",,10.1016/j.tetlet.2009.11.013,2009-11-12,0.5941378462608561
Synthesis,Tetrathiafulvalene: A Convenient Large-Scale (20 g) Synthesis,"All articles of this category A cheap, high yielding large-scale (20 g) synthesis of tetrathiafulvalene is reported. An efficient, high-yielding, 20 g-scale synthesis of TTF is reported: a practical advantage of this route is that no chromatography is required at any stage",10.1055/s-1997-1209,1997-04-01,0.5941366030067763
Journal of the American Chemical Society,Total Synthesis of (+)-Haperforin G,A concise chemical synthesis of (+)-haperforin G in 20 steps from commercially available starting materials is achieved with the integration of the Co-catalyzed intramolecular Pauson–Khand reaction for the stereoselective construction of cyclopentanone bearing an all-carbon quaternary stereogenic center at the bridge-head position and the light-initiated photocatalysis for convergent and asymmetric cross-coupling of the unstabilized C(sp 3 )-radical with an enone. The developed chemistry paves the way to synthesizing structurally diverse analogs of haperforin G ( 6 ).,10.1021/jacs.0c10122,2020-11-05,0.594131980591292
Tetrahedron,Asymmetric synthesis of carbohydrates: Synthesis of 2-deoxy-D- and 2-deoxy-L-xylofuranosides from a simple achiral precursor,,10.1016/s0040-4039(00)73487-3,1994-09-01,0.5941305184544269
Tetrahedron,"A new method for the synthesis of carba-sugar enones (gabosines) using a mercury(II)-mediated opening of 4,5-cyclopropanated pyranosides as the key-step",,10.1016/j.tetlet.2006.07.023,2006-08-02,0.5941290102082666
Journal of Organic Chemistry,"Synthesis of CMe<sub>2</sub>CF<sub>3</sub>-Containing Heteroarenes via Tandem 1,1-Dimethyltrifluoroethylation and Cyclization of Isonitriles","A tandem 1,1-dimethyltrifluoroethylation and cyclization of isonitriles with 3,3,3-trifluoro-2,2-dimethylpropanoic acid was developed. This protocol provides the efficient synthesis of a series of previously unknown CMe 2 CF 3 -containing heteroarenes, which are potentially useful in the drug discovery process.",10.1021/acs.joc.8b02506,2018-11-23,0.5941160512823884
Organic Letters,Asymmetric Hydrogenation of Tetrasubstituted Cyclic Enones to Chiral Cycloalkanols with Three Contiguous Stereocenters,A highly efficient iridium-catalyzed asymmetric hydrogenation of tetrasubstituted cyclic enones has been developed for the enantioselective synthesis of chiral cycloalkanols with three contiguous stereocenters. The C═O and C═C bonds of the enone substrates were hydrogenated sequentially in one pot with excellent enantioselectivity (92 to >99% ee) and diastereoselectivity (dr 95:5 to >99:1). The reaction provided a practical approach to all of the stereoisomers of the antiulcer drug rosaprostol.,10.1021/acs.orglett.7b01343,2017-05-31,0.5941132104986705
Organic Letters,Cyclopentanone Ring Expansion Leading to Functionalized δ-Lactams:  Short Synthesis of Simple Sedum Alkaloids,"Monosubstituted epoxides react with (cyclopentenyloxy)trimethylsilane to afford, after subsequent oxidative fragmentation, a pair of diastereomeric 8-membered iodolactones. When these lactones are separately treated with sodium azide, followed by reduction over Lindlar's catalyst, lactone ring contraction yields 6-membered monosubstituted lactams. When (R)-1,2-epoxypentane is used in this 5 + 3 - 2 overall ring expansion sequence, one final step involving delta-lactam to piperidine reduction yields natural (-)-halosaline and (-)-epihalosaline in five steps and 12% and 23% overall yields, respectively.",10.1021/ol070960r,2007-06-12,0.5941116721349585
Journal of Organic Chemistry,Stereoselective Synthesis of (+)-Aspidofractinine,"We describe the synthesis of (+)-aspidofractinine, the enantiomer of a naturally occurring alkaloid of the kopsane family. Key features of the synthesis include a stereospecific cyanate to isocyanate rearrangement on a chiral scaffold, a ring-closing alkene metathesis to cleave the chiral auxiliary, and a chemoselective cyclopropanation to introduce the quaternary carbon at position 7 of aspidofractinine.",10.1021/jo9009497,2009-07-15,0.5941085855155143
Tetrahedron,Application of directed metalation in synthesis. Part 7: Synthesis of suitably functionalised benzo[b]thiophenes as key intermediates in the synthesis of benzothienopyranones,,10.1016/j.tetlet.2005.01.038,2005-01-27,0.5941060390355183
Tetrahedron,An efficient one-pot synthesis of 3-aminohydantoin and 3-aminodihydrouracil derivatives,,10.1016/s0040-4039(99)02286-8,2000-02-01,0.5940987446535374
Tetrahedron,"An efficient one-pot synthesis of acenaphtho[1,2-b]indolindeneone and acenaphtho[1,2-b]indoldione derivatives",,10.1016/j.tetlet.2023.154578,2023-06-02,0.5940987446535374
Angewandte Chemie International Edition,Enantioselective Total Synthesis of (+)-Gelsemine: Determination of Its Absolute Configuration,The unique hexacyclic cagelike structure of (+)-gelsemine (1) has been accomplished. The first enantioselective total synthesis of this alkaloid features a facile construction of the bicyclo[3.2.1] core by means of two rearrangement reactions and the efficient formation of the pyrrolidine ring by an intramolecular Michael addition. Bn=Benzyl.,10.1002/1521-3773(20001117)39:22<4073::aid-anie4073>3.0.co;2-v,2000-11-17,0.5940981635262783
Synlett,Efficient Synthesis of Tetrahydroxylated Pyrrolizidines by Nitrone Cycloaddition Leading to Unnatural Stereoisomers of 7-Deoxycasuarine,"A convenient and efficient method has been used for the synthesis of ten new tetrahydroxylated pyrrolizidines 12a,b, 13a-c, 14a,b, and 15a-c starting from sugar-derived cyclic nitrones prepared from d-xylose, d-arabinose, d-ribose, and l-arabinose, through a five-step reaction sequence. Pyrrolizidine 12a is an enantiomer of 7-deoxycasuarine and pyrrolizidine 12b an enantiomer of the as yet unknown 7-deoxyuniflorine A. This method expands the scope of nitrone cycloadditions and is flexible enough for the synthesis of various stereoisomers of highly polyhydroxylated pyrrolizidines.",10.1055/s-0030-1260933,2011-07-01,0.5940947707737131
Journal of Organic Chemistry,"A Dirhodium(II)−Carbenoid Route to (−)- and (+)-Geissman−Waiss Lactone:  Synthesis of (1<i>R</i>,7<i>R</i>,8<i>R</i>)-(−)-Turneforcidine","(-)- and (+)-Geissman-Waiss lactone, 4b, was efficiently prepared via the intramolecular C-H insertion reaction of the chiral nonracemic diazoacetates (-)-5a and (+)-5b catalyzed by dirhodium(II) tetrakis[methyl (5R and 5S)-3-phenylpropanoyl-2-imidazolidinone-5-carboxylate]. The cyclization was found to proceed with excellent regioselectivity and cis-diastereoselectivity. The bicyclic lactone (-)-4b was successfully used in the synthesis of the necine base, (-)-turneforcidine 2.",10.1021/jo010753j,2001-11-15,0.5940927718866134
Organic Letters,Pd(II)-Catalyzed One-Step Construction of Cycloalkane-Fused Indoles and Its Application in Formal Synthesis of (±)-Aspidospermidine,"A highly efficient, redox-free Pd(II)-catalyzed tandem cyclization reaction initiated by intramolecular aminopalladation of alkynes followed by nucleophilic addition to nitriles is developed. This method provides a versatile approach for the synthesis of six- to eight-membered ring-fused indoles in one step and has also shown advantages in the formal synthesis of (±)-aspidospermidine.",10.1021/ol500662f,2014-03-21,0.5940919250632947
Synthesis,Synthesis of Novel Pyrazine-Substituted 1H-Pyrrole-2-carboxamides and Related Tethered Heterocycles,"Abstract As part of a drug discovery program, 4-pyrazin-2-yl-1H-pyrrole-2-carboxamides were accessed along with a number of bicyclic analogues. Routes to these compounds were largely absent from the scientific literature. The synthesis of a 4-(pyrazin-2-yl)-1H-pyrrole-2-carboxamide and several fused bicyclic analogues all using standard procedures (SNAr, borylation, C–C cross couplings, hydrolysis, amide bond formation, cyclisation, halogenation, and alkylation) from readily available starting materials is reported. The synthetic sequences range from 4–12 steps per final compound, with yields of isolated intermediates ranging from 20 to ∼100%.",10.1055/s-0040-1719873,2022-01-26,0.5940858606831875
Organic Letters,A Novel Supermolecular Tetrameric Vanadate-Selective Colorimetric and “Off–On” Sensor with Pyrene Ligand,"Tris(2-((ethylimino)methyl)pyren-1-ol)amine (1) was synthesized and introduced as the first tetrameric vanadate fluorescence sensor, the entire binding of which was successfully accomplished in two steps with distinct colorimetric changes and ""off-on"" fluorescent enhancement.",10.1021/ol200846a,2011-04-22,0.5940848224148912
Organic Letters,Palladium-Catalyzed Synthesis of Diarylmethanes: Exploitation of Carbanionic Leaving Groups,"A novel route to the synthesis of diarylmethanes via a Pd-catalyzed alpha-arylation of benzyl ketones is reported. By harnessing the inherent reactivity of enolates, it is possible to circumvent the need for a transmetalating reagent such as boron for the coupling. Additionally, the two phenyl rings of the intermediate are exploited to stabilize the high-energy carbanionic leaving group in a straightforward synthesis.",10.1021/ol900874z,2009-05-20,0.5940759901786852
Tetrahedron,Diazo-sulfones and -nitriles in oxazole synthesis; three step preparation of a bis-oxazole,,10.1016/0040-4039(93)88041-g,1992-12-01,0.5940755671371919
Angewandte Chemie International Edition,Second‐Generation Synthesis of Azadirachtin: A Concise Preparation of the Propargylic Mesylate Fragment,"A second bite of the apple: A new and highly efficient synthesis of the propargylic mesylate fragment of azadirachtin has been accomplished (see scheme; Bn = benzyl, Ms = methanesulfonyl, PMB = para-methoxybenzyl, TBDPS = tert-butyldiphenylsilyl). An enantioselective catalytic hetero Diels-Alder reaction sets up the stereocenter at C15, which then controls the installation of the remaining functionality in a total of only 17 steps.",10.1002/anie.200805395,2009-01-12,0.5940703705393574
Organic Letters,"An Expedient Route to 2,3-Substituted and Fused Benzo[<i>a</i>]quinolizine-4-thione Framework via Ring Annulation with <i>β</i>-Oxodithioesters","[figure: see text] An efficient highly convergent route to hitherto unreported 2,3-substituted and annulated benzo[a]quinolizine-4-thiones 3 has been developed. The methodology involves ring annulation of 3,4-dihydro-6,7-dimethoxy-1-methylisoquinoline 1 with a variety of readily accessible acyclic and cyclic beta-oxodithioesters 2 in the presence of triethylamine in refluxing benzene. These benzo[a]quinolizine-4-thiones can be readily converted to the corresponding benzo[a]quinolizine-4-ones 5 via dethiomethylative hydrolysis of the respective benzo[a]quinolizinium salts 4 obtained by alkylation of 3 with methyl iodide.",10.1021/ol000354v,2001-01-01,0.5940702007681192
European Journal of Organic Chemistry,A Formal Synthesis of (−)-Paroxetine by Enantioselective Ring Enlargement of a Trisubstituted Prolinol,"A ring expansion and a radical dehalogenation have been used as the key steps in a formal total synthesis of (−)-paroxetine. The substituted piperidine ring precursor of (−)-paroxetine was generated by means of a stereoselective ring expansion of prolinol. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)",10.1002/1099-0690(200211)2002:21<3543::aid-ejoc3543>3.0.co;2-0,2002-10-18,0.5940698492845639
European Journal of Organic Chemistry,Chromium-Templated Synthesis of Densely Substituted Distorted Arenes − Intramolecular Benzannulation of [(Alkynylaryl)alkenyl]carbene Complexes to Planar-Chiral Hydroquinoid [2.2]Heterametacyclophanes,"{[(meta-Alkynylphenyl)alkenyl]carbene}chromium compounds 1 and 2 have been synthesized by four-step (or five-step) and seven-step sequences, starting from 3-halophenol or 3-haloaniline, respectively. This approach, involving high-yielding Takai reactions and lithium cuprate additions, provides a novel and straightforward route to [(alkynylaryl)alkenyl](methoxy)carbene complexes. Upon gentle warming in tetrahydrofuran, (carbene)chromium compounds of this type undergo intramolecular benzannulation to give novel [2.2]heterametacyclophanes 21 and 22, bearing two chiral planes arising from the unsymmetrical substitution patterns both of the cyclophane skeleton and of the newly formed, Cr(CO)3-coordinated benzohydroquinone deck.",10.1002/1099-0690(20021)2002:1<39::aid-ejoc39>3.0.co;2-9,2002-01-01,0.5940662503750929
Synlett,New Approach for the Efficient Synthesis of Carbamate-Tethered Glycosylated Amino Acids and Their Insertion into Peptides,"An efficient two-step route for the synthesis of carba­mate-tethered glycosylated amino acids by coupling of oxycarbonyl chlorides derived from side-chain hydroxyl group of N α-Fmoc-Ser, Thr, Tyr and homoserine (Hser) with appropriately protected sugar-1-amine has been described. The utility of these neoglycoamino acids as building blocks for the synthesis of neoglycopeptides possessing the carbamate moiety has been demonstrated.",10.1055/s-2008-1032087,2008-02-12,0.5940632994909597
Journal of Organic Chemistry,"Synthesis of<scp>l</scp>-Daunosamine Derivatives on the Basis of the Asymmetric Dihydroxylation of 3-((<i>E</i>)-1-Propenyl)-4,5-dihydroisoxazole","Methyl l - N,O -diacetyldaunosaminide was prepared from 3-nitro-4,5-dihydroisoxazole in 8.5% overall yield. A key step in the synthesis involved the AD reaction of ( E )-3-(1-propenyl)-4,5-dihydroisoxazole ( 2b ), affording the corresponding diol in 76% yield (92% ee). A second key step involved reductive cleavage of the dihydroisoxazole 4a and subsequent N -acetylation to afford separable diastereomeric γ-(acetylamino)alcohols 7a and 8a in 62% yield (72:28, 7a/8a ). Swern oxidation of 7a and subsequent methanolysis followed by acetylation provided methyl l - N,O -diacetyldaunosaminide as an anomeric mixture. The AD reactions of chiral alkenyl dihydroisoxazole 16 with (DHQ) 2 −PHAL and (DHQD) 2 −PHAL afforded diastereomeric diol products, isolated as the acetates 18 and 19 (98:2 and 5:95 ratios, respectively, depending on the chiral auxiliary).",10.1021/jo962293d,1997-05-01,0.5940587548110856
Tetrahedron,"Synthetic studies on capnellol family : an improved synthesis of Δ9(12)-capnellene-3β,8β,10α-triol and the first total synthesis of Δ9(12)-capnellene-β,8β,10α,14-tetrol",,10.1016/s0040-4039(00)85180-1,1986-01-01,0.5940572417350451
Organic Letters,"An Expeditious Route to Both Enantiomers of All Carbon Quaternary Stereocenters at C-3 Carbon of Lactams via [3,3]-Sigmatropic Rearrangement: Total Synthesis of (−)-Physostigmine","A diastereoselective route to all carbon quaternary stereocenters at the C-3 position of cyclic lactams has been developed via Johnson-Claisen rearrangement of γ-hydroxy-α, β-unsaturated lactams. It has been observed that olefin geometry plays an important role in the development of the absolute stereochemistry of the product. The dependence of the product configuration on the olefin geometry is explained by postulating probable transition states. The success of this method has been shown for the multigram scale synthesis of these substituted lactams from commercially available cheap starting materials. The synthetic usefulness of this method is also demonstrated by carrying out the total synthesis of (-)-physostigmine.",10.1021/ol503766y,2015-02-11,0.5940566683405999
European Journal of Organic Chemistry,Total Synthesis and Biological Evaluation of Seiricuprolide and Pestalotioprolide B,"Abstract The first total syntheses of seiricuprolide and pestalotioprolide B, rare 14‐membered α,β‐unsaturated macrolides embedding a chiral epoxide motif, were achieved in 17 steps with 1.9 % and 1.6 % overall yields, respectively. Our synthesis featured the key Shiina macrolactonization to construct the 14‐membered macrocyclic skeleton, Wittig olefination to generate the ( E )‐α,β‐unsaturated ester and selective reduction of advanced chiral propargylic alcohol intermediate to enable the exclusive formation of Z ‐ or E ‐olefin at C8−C9. Synthetic seiricuprolide and pestalotioprolide B were evaluated for their cytotoxic activity against the HCT116 colon cancer cell line as well as their inhibitory effect on CFTR chloride channel activity in human intestinal epithelial (T84) cells. Preliminary structure–activity relationship suggested that the C5−C6 β‐epoxide moiety suppressed both biological activities.",10.1002/ejoc.202300034,2023-02-15,0.5940563878783766
Journal of the American Chemical Society,Total Syntheses of Anominine and Tubingensin A,"A divergent strategy for the total syntheses of the indole terpenoid anominine (1) and its natural congener tubingensin A (2) has been developed. The common intermediate 11 bearing all of the required stereogenic centers for both natural products was first assembled by employing a Ueno-Stork radical cyclization and a Sc(OTf)(3)-mediated Mukaiyama aldol reaction to form the key C-C bonds in a stereocontrolled manner. The route to anominine features a radical deoxygenation followed by an efficient side-chain installation, while the path to tubingensin A exploits a CuOTf-promoted 6π-electrocyclization/aromatization sequence to forge the central region of the pentacyclic scaffold.",10.1021/ja302765m,2012-04-26,0.5940401871945102
Journal of Organic Chemistry,Synthesis of (−)-Hamigeran B,"The synthesis of (-)-hamigeran B has been achieved, based on a new approach to cyclopentane construction, the rhodium-mediated intramolecular C-H insertion of alpha-aryl-alpha-diazoketones. The endo-isopropyl group was installed by selective hydrogenation of a cyclopropylidene substituent.",10.1021/jo8010683,2008-09-05,0.594038928446032
Tetrahedron,"Synthesis of a potent β-lactamase inhibitor- 1,1-dioxo-6-(2-pyridyl)methylenepenicillanic acid and its reaction with sodium methoxide",,10.1016/s0040-4039(00)84819-4,1986-01-01,0.5940340763060312
Tetrahedron,Total synthesis of thienamycin: a new approach from aspartic acid,,10.1016/s0040-4039(00)87324-4,1982-01-01,0.5940272635156916
Organic Letters,"Two-Step Synthesis of Difluoromethyl-Substituted 2,3-Dihydrobenzoheteroles","3-Difluoromethylated 2,3-dihydrobenzoheteroles, 2,3-dihydrobenzofurans, 2,3-dihydrobenzothiophenes, and indolines were readily synthesized from ortho-heterosubstituted bromobenzenes, 2-bromophenols, 2-bromobenzenethiols, and 2-bromoanilines, respectively, in two steps: (1) γ-selective allylic substitution of 3-bromo-3,3-difluoropropene with heteronucleophiles and (2) intramolecular radical cyclization of the resulting 3,3-difluoroallylic compounds.",10.1021/ol5001582,2014-02-19,0.5940225905580135
Organic Process Research & Development,Identification and Control of a Process-Related Impurity in the Chlorination of 3-Hydroxy-3-carbacephem,"A process for the synthesis of carbacephem key intermediate (4-nitrophenyl)methyl,7-amino-1-carba(dethia)-3-chloro-3-cephem-4-carboxylate, monohydrochloride (1 ) via chlorination and deacylation employing chlorotriphenoxyphosphonium chloride [(PhO) 3 P + ClCl - ] has been described. The most difficult problem encountered during the process development was the formation of an impurity 2, which has been isolated, identified, and controlled by modifying the reaction conditions.",10.1021/op034026x,2003-05-15,0.5940208527959184
Journal of Organic Chemistry,Synthetic Preparation of the Macrocyclolipopeptide Dysoxylactam A for Potent P-glycoprotein Inhibition,"High Resolution Image Download MS PowerPoint Slide In 2019, the cyclolipopeptide dysoxylactam A was isolated and reported to be a potent inhibitor of the drug efflux pump P-glycoprotein and demonstrated the ability to reverse multidrug resistance in cancer cell lines. Herein, we report a reliable and flexible route toward dysoxylactam A, which features key transformations such as the Paterson 1,2- anti aldol reaction, an sp 3 -sp 3 Fu–Suzuki coupling, asymmetric allylation, and the Corey–Nicolaou macrolactonization. All the data obtained on the synthesized natural product matched those of the authentic material.",10.1021/acs.joc.5c01765,2025-10-16,0.5940163486947302
Synlett,"Synthesis of Optically Active Hydroxyalkyl Cycloheptatrienes: A Key Step in the Total Synthesis of 6,11-Methylene-LXB4","Abstract Starting from methyl cycloheptatrienyl-1-carboxylate, 6-acylation was successfully achieved employing glutaryl chloride in the presence of AlCl3 under controlled reaction conditions to furnish keto carboxylic acid product. After protection of this keto carboxylic acid as tert-butyl ester, reagent-controlled enantioselective reductions delivered configuration-defined methyl-6-hydroxylalkyl cycloheptatriene-1-carboxylates with up to 80% ee. Whereas simple NaBH4 reduction of the keto carboxylic acid and subsequent lactonization afforded a methyl-6-tetrahydropyranonyl cycloheptatriene-1-carboxylate. Resolution using chiral HPLC delivered the product enantiomers with up to &gt;99% ee Finally, ECD analyses enabled structure elucidation. The products are used as key intermediates in enantioselective 6,11-methylene-lipoxin B4 syntheses.",10.1055/s-0040-1707282,2020-09-24,0.59401198266982
Journal of the American Chemical Society,Total Synthesis and Structural Elucidation of Azaspiracid-1. Final Assignment and Total Synthesis of the Correct Structure of Azaspiracid-1,"The molecular structure of azaspiracid-1, a neurotoxin isolated from mussels, has been elucidated by total synthesis which also enriched its supplies. The degradatively derived fragments of this marine biotoxin, compounds 5 (EFGHI), 6 (FGHI), and 40 (ABCD), were matched with synthetic materials, thus confirming their structural identities. Based on this detective work, a new structure of azaspiracid-1 (i.e., 1) was proposed and constructed by total synthesis. The final strategy for the total synthesis of azaspiracid-1 featured a dithiane anion (C(21)-C(27) fragment) reacting with a pentafluorophenol ester (C(1)-C(20) fragment) followed by a Stille-type union of an advanced allylic acetate substrate (C(1)-C(27) fragment) with a vinyl stannane as the main coupling processes to assemble the carbon skeleton of the molecule. In addition to the total synthesis of azaspiracid-1 (1), the syntheses of its C(1)-C(20) epimer (2) and of several truncated analogues for biological investigations are described.",10.1021/ja054750q,2006-02-02,0.5940077089590682
Journal of Organic Chemistry,Stereoselective Synthesis of Tricyclic β-Lactam by Sulfoxide-Directed Oxidative Lactonization from an Accessible Cephalosporin Intermediate,"Tricyclic β-lactam antibiotics show significant antibacterial activities against carbapenem-resistant Enterobacterales (CREs), but the synthesis of a key intermediate for tricyclic β-lactam antibiotics requires eight steps from penicillin with a low total yield of 3% via non-stereoselective lactone formation. Here we report the stereoselective synthesis of the tricyclic β-lactam core by sulfoxide-directed oxidative lactonization from an accessible and inexpensive commercially available cephalosporin intermediate in 23% total yield in six steps.",10.1021/acs.joc.2c01113,2022-07-29,0.5939938062711803
Tetrahedron,"Dihydrobenzofurans as cannabinoid receptor ligands from Cordyceps annullata, an entomopathogenic fungus cultivated in the presence of an HDAC inhibitor",,10.1016/j.tetlet.2012.02.088,2012-02-24,0.5939910594718221
Tetrahedron,"N-Arylation of a hindered indoline as a route to 2-(2-methyl-1-(4-oxo-3,4-dihydrophthalazin-1-yl)-1H-indol-3-yl)acetic acid derivatives",,10.1016/j.tetlet.2011.08.169,2011-09-11,0.5939890111006405
Tetrahedron,A novel route to optically active dihydropyrans and 3-methylenetetrahydrofurans,,10.1016/s0040-4039(00)95174-8,1989-01-01,0.5939873562985007
Journal of the American Chemical Society,Enantioselective Total Syntheses of (−)-Taiwaniaquinone H and (−)-Taiwaniaquinol B by Iridium-Catalyzed Borylation and Palladium-Catalyzed Asymmetric α-Arylation,"We report a concise, enantioselective total synthesis of (-)-taiwaniaquinone H and the first enantioselective total synthesis of (-)-taiwaniaquinol B by a route that includes asymmetric palladium-catalyzed α-arylation of a ketone with an aryl bromide that was generated by sterically controlled halogenation via iridium-catalyzed C-H borylation. This asymmetric α-arylation creates the benzylic quaternary stereogenic center present in the taiwaniaquinoids. The synthesis was completed efficiently by developing a Lewis acid-promoted cascade to construct the [6,5,6] tricyclic core of an intermediate common to the synthesis of a number of taiwaniaquinoids. Through the preparation of these compounds, we demonstrate the utility of constructing benzylic quaternary stereogenic centers, even those lacking a carbonyl group in the α-position, by asymmetric α-arylation.",10.1021/ja110215b,2011-01-26,0.5939865519541025
Green Chemistry,Green synthesis of CdS/Ni <sub> <i>x</i> </sub> S <sub> <i>y</i> </sub> nanoparticles as a route towards sustainable and scalable photocatalysts,"If hydrogen evolution photocatalysis are to be deployed at industrial scale, the synthesis of these photocatalytic materials must be both economically and environmentally scalable.",10.1039/d2gc03361e,2022-12-02,0.5939826250020855
Synlett,The Phenanthrenone Approach to Opium Alkaloids: Formal Total Synthesis of Morphine by Sigmatropic Rearrangement,All articles of this category The synthesis of morphine alkaloids involving sigmatropic rearrangements and novel ring closures of aromatic methyl pentenyl ethers is reported. morphine alkaloids - Claisen rearrangement - total synthesis,10.1055/s-1997-6135,1997-06-01,0.5939770670201532
Journal of Organic Chemistry,I<sub>2</sub>-Cs<sub>2</sub>CO<sub>3</sub> Mediated Intramolecular C2-Amination and Oxidative Rearrangement Cascade of C-3 Phenylthio Indoles: A Route to Synthesize Thiosulfonate-Embedded 2-Iminoindolin-3-ones,"An efficient, transition-metal-free protocol employing I 2 /Cs 2 CO 3 for the synthesis of thiosulfonate containing 2-iminoindolin-3-ones motifs has been developed from C-3 phenylthio indoles. The reaction proceeded through intramolecular cyclization involving C–N bond formation, leading to the formation of indole-fused benzothiazines as a key intermediate. Remarkably, Cs 2 CO 3 played a crucial role in the reaction as an oxygen source, enabling oxidative rearrangement with [1,4]-sulfonyl migration to furnish the final products with the formation of multiple functional groups such as C═O, C═N, and S–SO 2 .",10.1021/acs.joc.4c00056,2024-03-29,0.5939725769842148
European Journal of Organic Chemistry,New Synthetic Routes for the Preparation of 2′-C-Methylene Nucleosides,"Two new routes to 2′,3′-dideoxy-2′-C-methylene nucleoside analogs have been developed. The first is based upon the coupling reaction of a 1-O-acetyl 2-C-(methylphenylsulfinyl) sugar with a silylated base under Vorbrüggen conditions, followed by thermal elimination of phenylsulfinic acid. The second route involved a condensation of a silylated base with a (π-allyl)palladium complex derived from a 2-C-acetoxymethyl furanoid glycal.",10.1002/(sici)1099-0690(199811)1998:11<2417::aid-ejoc2417>3.0.co;2-c,1998-11-01,0.593971004434687
European Journal of Organic Chemistry,New Synthetic Routes for the Preparation of 2′-C-Methylene Nucleosides,"Two new routes to 2′,3′-dideoxy-2′-C-methylene nucleoside analogs have been developed. The first is based upon the coupling reaction of a 1-O-acetyl 2-C-(methylphenylsulfinyl) sugar with a silylated base under Vorbrüggen conditions, followed by thermal elimination of phenylsulfinic acid. The second route involved a condensation of a silylated base with a (π-allyl)palladium complex derived from a 2-C-acetoxymethyl furanoid glycal.",10.1002/(sici)1099-0690(199811)1998:11<2417::aid-ejoc2417>3.3.co;2-3,1998-11-01,0.593971004434687
Angewandte Chemie International Edition,"Enantioselective Total Synthesis of 3β‐Hydroxy‐7β‐kemp‐8(9)‐en‐6‐one, a Diterpene Isolated from Higher Termites","The first total synthesis of the title diterpene was accomplished starting from the Wieland-Miescher ketone. A diastereoselective sulfa-Michael addition enabled the generation of the delicate β,γ-unsaturated ketone moiety, while the tetracyclic kempane skeleton was readily constructed through domino metathesis.",10.1002/anie.201708561,2017-09-29,0.5939680531946974
European Journal of Organic Chemistry,New Oxazole‐Based Conformationally Restricted Peptidomimetics: Design and Synthesis of Pseudopeptides,A general synthesis of a new class of optically active amino acids containing an oxazole moiety is described along with a strategy for their insertion into a peptidomimetic chain. A modified portion of endothelin-1 is prepared as a potential receptor antagonist. The procedure presented is based on readily available materials and can be performed in multigram quantities.,10.1002/1099-0690(200009)2000:18<3217::aid-ejoc3217>3.0.co;2-#,2000-09-01,0.5939574224335976
Synthesis,Synthesis of Angularly Fused (Homo)triquinane-Type Hydantoins as Precursors of Bicyclic Prolines,An efficient strategy for a four-step synthesis of angularly fused tricyclic hydantoins as suitable precursors of cis -fused bicyclic α-amino acids is developed by combining a highly diastereoselective Bucherer–Bergs reaction of 2-alkenylcycloalkanones and a regiospecific selenium-induced closure of pyrrolidine ring. This methodology was applied in a five-step synthesis of bicycloproline derivatives in high overall yield. The method could be used for the multigram preparation of free conformationally constrained bicyclic α-amino acids with two points of diversity (size of cycloalkyl ring and substituent at the pyrrolidine ring).,10.1055/s-0035-1561285,2015-12-15,0.5939528420705372
Organic Letters,"Asymmetric Total Syntheses of (−)-Fennebricin A, (−)-Renieramycin J, (−)-Renieramycin G, (−)-Renieramycin M, and (−)- Jorunnamycin A via C–H Activation",Collective total synthesis of five tetrahydroisoquinoline alkaloids including the first total synthesis of (-)-fennebricin A and (-)-renieramycin J has been accomplished. The synthesis features employing a single common amino acid to symmetrically construct the pentacycle of title alkaloids. The palladium-catalyzed arylation of alanine-derived amide developed by Yu was tactically utilized to afford unnatural amino acid building block rapidly and practically. The structure of synthetic (-)-renieramycin M has been confirmed by single crystal X-ray analysis for the first time.,10.1021/acs.orglett.0c01493,2020-05-21,0.5939477257373975
Tetrahedron,"Efficient synthesis of chiral α,β-epoxyesters via a cyclic sulfate intermediate",,10.1016/s0040-4039(98)00190-7,1998-04-01,0.5939364517258664
Synlett,"3-Substituted and 2,3-Disubstituted Cyclopentanones via an Asymmetric Tandem 1,4-Addition/Dieckmann Cyclization","A new stereoselective method for the synthesis of 3-substituted and 2,3-disubstituted cyclopentanones is described. The key step is the 1,4-addition of a cuprate to a chilar Michael-acceptor derived from (-)-8-phenylmenthol or the Helmchen auxiliary followed by Dieckmann cyclization of the obtained chiral enolates. The resultant 2,3-cyclopentanones can be transformed after methanolysis and demethoxycarbonylation to the related 3-substituted ­cyclopentanones.",10.1055/s-2003-45008,2004-01-01,0.593936313909562
Tetrahedron,Cyclisation of dinitriles by sodium alkoxides a new synthesis of naphthyridines,,10.1016/s0040-4039(00)71814-4,1975-01-01,0.5939347821021964
Tetrahedron,Intramolecular electrolytic reductive coupling of activated olefins: a novel route to cyclic compounds,,10.1016/s0040-4039(00)72913-3,1966-01-01,0.5939268029352262
Organic Letters,Enantioselective Total Synthesis of (−)-Erinacine B,The first enantioselective total synthesis of (-)-erinacine B has been achieved. Our approach features convergent construction of the 5-6-7 tricyclic cyathane core system via chiral building blocks prepared using asymmetric catalysis developed by us and highly stereoselective construction of all stereogenic centers in the aglycon. [reaction: see text].,10.1021/ol0628816,2006-12-15,0.5939101933167509
Journal of Organic Chemistry,Total Synthesis of Dysiherbaine,"A convergent total synthesis of the marine natural product dysiherbaine was accomplished. The key steps of the synthesis are an alkylation at the gamma-carbon of a protected glutamate with a highly substituted pyran derived from mannose, which was followed by a ring-contraction cascade reaction, which simultaneously gave the tetrasubstituted carbon and the hexahydrofuro[3,2-b]pyran ring system of the natural product.",10.1021/jo0107610,2002-03-30,0.5939095289476316
Tetrahedron,"Practical synthesis of the calcimimetic agent, cinacalcet",,10.1016/j.tetlet.2007.11.030,2007-11-28,0.5939087990745834
Tetrahedron,"Synthesis of 4-aza analog of ramelteon: a novel tricyclic 1,6,7,8-tetrahydro-2H-cyclopenta[d]furo[2,3-b]pyridine derivative as melatonin receptor ligand",,10.1016/j.tetlet.2011.03.147,2011-04-15,0.5939086988358906
European Journal of Organic Chemistry,"Stereoselective Approach to 2,6‐Disubstituted Piperidin‐3‐ol: Synthesis of (–)‐Deoxoprosopinine and (+)‐Deoxoprosophylline","Abstract A simple and highly efficient approach to an enantioenriched 2,6‐disubstituted piperidin‐3‐ol skeleton is developed from an aldehyde as a starting material by using organocatalytic and asymmetric dihydroxylation as the key steps. Its application to the total synthesis of (–)‐deoxoprosopinine and (+)‐deoxoprosophylline is also reported.",10.1002/ejoc.201402363,2014-06-23,0.5939070167915093
Synthesis,"An Improved Synthesis of<i>N</i>-Substituted 1-Aryl-3-oxo-1,2,3,4-tetrahydroisoquinolines",,10.1055/s-1982-29752,1982-01-01,0.5939050552862154
Organic Process Research & Development,Carry Over of Impurities: A Detailed Exemplification for Glycopyrrolate (NVA237),"The original synthesis of glycopyrrolate (NVA237) was revised and shortened into an essentially one-pot process. Without isolating the intermediates, their purification became obsolete, thereby increasing the possibility of the carry over of impurities. For that reason, the actual, potential, and theoretical impurities of the starting materials cyclopentyl mandelic acid and 1-methyl-pyrrolidin-3-ol as well as byproducts which may occur during the synthesis were thoroughly investigated; furthermore, their transformation to possible impurities in the drug substance along the new synthetic route was performed to exclude them as actual impurities in the drug substance with certainty. The question is raised how detailed such investigation—which are fairly manageable for a simple product like glycopyrrolate—need to be.",10.1021/op3001788,2012-10-08,0.5939032141280794
Journal of Organic Chemistry,Total Synthesis of the Resorcyclic Acid Lactone Spiroketal Citreoviranol,"The first total synthesis of resorcyclic acid lactone spiroketal citreoviranol (1) is described. The synthesis was completed in nine steps and via Sonogashira cross-coupling, gold-catalyzed cyclization, and an unusual base-induced ketalization. The relative and absolute stereochemistry of citreoviranol was unambiguously confirmed using 2D NMR spectroscopy and X-ray crystallography.",10.1021/acs.joc.6b01503,2016-08-09,0.5938961212238802
Tetrahedron,"Stereoselective synthesis of the 1,N2-deoxyguanosine adducts of cinnamaldehyde. A stereocontrolled route to deoxyguanosine adducts of α,β-unsaturated aldehydes",,10.1016/j.tetlet.2003.08.006,2003-09-01,0.5938944667657469
Organic Process Research & Development,"Development of a Reliable Low-Loading Palladium-Catalyzed Monoamination Process for the Large-Scale Synthesis of 3-Bromo-2,5-difluoroaniline","The development of a manufacturing process for the multikilogram synthesis of 3-bromo-2,5-difluoroaniline required as a starting material for the anticancer KRAS G12C inhibitor AZD4625 is described. Two potential synthetic routes to this aniline were identified involving Fe/HCl dissolving metal reduction of the nitro group of 1-bromo-2,5-difluoro-3-nitrobenzene or Pd(0)-catalyzed monoamination of 1,3-dibromo-2,5-difluorobenzene with benzophenone imine to give a haloaryl-imine intermediate that was then hydrolyzed. Optimization of the Pd(0) catalyzed C–N bond-forming step and associated mechanistic studies identified that 0.5 mol % Pd(dba) 2 /Xantphos and four equivalents of K 3 PO 4 in i PrOAc at 80 °C could be used to produce 100 kg batches of a haloaryl-imine intermediate. Solutions of this imine in i PrOAc were then hydrolyzed through treatment with aqueous HCl allowing the desired aniline 1 to be isolated as its crystalline HCl salt. Process improvements include reduction of the amount of expensive Pd(dba) 2 precatalyst used from 1.5 to 0.5 mol %, with i PrOAc used as a process-friendly solvent that allowed the C–N bond formation and imine hydrolysis steps to be telescoped into a single process. Detailed mechanistic investigations identified that use of excess K 3 PO 4 as a heterogeneous base was necessary to minimize catalyst deactivation and impurity formation in the low-loading Pd(0)-catalyzed C–N bond-forming step.",10.1021/acs.oprd.5c00103,2025-08-19,0.5938904273733695
Synthesis,"Palladium-Catalyzed Direct α-Arylation of p-Methoxybenzyl-Protected S,S-Dimethylsulfoximine","Sulfoximines have recently gained considerable recognition as an important structural motif in the life sciences. This is especially true for (hetero)aryl-substituted S , S -dimethylsulfoximine derivatives, such as the marketed insecticide sulfoxaflor, as well as the clinical candidates­ PTEFb inhibitor BAY 1143572 and ATR inhibitor AZD 6738 for the treatment of cancer. Herein, the first palladium-catalyzed direct α-arylation of p -methoxybenzyl-protected S , S -dimethylsulfoximine using readily available (hetero)aryl bromides is reported. This new method provides a safe, short, and efficient approach to (hetero)aryl-substituted­ S , S -dimethylsulfoximine derivatives, an important class of bioactive compounds, demonstrated by application of this methodology to an improved synthesis of PTEFb inhibitor BAY 1143572.",10.1055/s-0036-1588894,2016-10-12,0.5938886004889202
Synthesis,Stereoselective Total Synthesis of (S)-Stigmolone: A Fruiting-Body-Inducing Pheromone,"The total synthesis of ( S )-stigmolone, a pheromone from the myxobacterium Stigmatella aurantiaca that induces the formation of fruiting bodies, is described. Sharpless asymmetric epoxidation followed by tert -butyldimethylsilyl trifluoromethanesulfonate/Hünig’s base mediated intramolecular hydride ion transfer reactions were used to install the C-5 stereogenic center. Commercially available isovaleraldehyde is used as a starting material.",10.1055/s-0036-1589471,2016-12-14,0.5938870055193272
Tetrahedron,Improved synthesis of N1-substituted orotic acid derivatives,,10.1016/j.tetlet.2013.05.136,2013-06-07,0.5938807428551
Journal of Organic Chemistry,Synthesis of Indoles from <i>o</i>-Haloanilines,A convenient method for the synthesis of indoles has been developed by the sequential orchestration of the cross-coupling reaction of o -haloaniline and PIFA oxidation of the resulting 2-alkenylanilines. A highlight of this two-step indole synthesis is a modular strategy which is applicable to both acyclic and cyclic starting materials. Particularly noteworthy is the regiochemistry that is complementary to the Fischer indole synthesis and related variants. Direct preparation of N –H indoles with no N -protecting group is also advantageous.,10.1021/acs.joc.3c01047,2023-07-06,0.5938806725568642
Journal of Organic Chemistry,Total Synthesis of Coraxeniolide-A,The first total synthesis of optically active coraxeniolide-A (1a) and 4-epi-coraxeniolide-A (1b) is described. The approach is highly stereoselective and flexible in the preparation of a wide variety of members of the xeniolide family. The use of the Grob-fragmentation was pivotal for the stereospecific elaboration of the nine-membered ring. Coraxeniolide-A (1a) was synthesized in 28 steps by using the Hajos-Parrish diketone 2 as starting material which is available enantiomerically pure.,10.1021/jo005582h,2000-12-01,0.5938773666759269
Tetrahedron,A new route to 3-deoxy-d-manno2-octulosonic acid: felkin-anh rule in radical chemistry,,10.1016/s0040-4039(00)79054-x,1992-05-01,0.5938726884370413
Organic Letters,"The First Regiospecific, Enantiospecific Total Synthesis of 6-Oxoalstophylline and an Improved Total Synthesis of Alstonerine and Alstophylline as Well as the Bisindole Alkaloid Macralstonine","A Wacker sequence has been modified to rapidly generate ring E of (-)-alstonerine, (+)-6-oxoalstophylline, and (-)-alstophylline via a domino process. This one-pot sequence provides facile entry into the dihydropyranyl enone unit of many Alstonia alkaloids. [structure: see text]",10.1021/ol051208y,2005-07-07,0.5938666697354251
Organic Process Research & Development,Manufacturing Process Development for Uprifosbuvir (MK-3682): A Green and Sustainable Process for Preparing Penultimate 2′-Deoxy-α-2′-Chloro-β-2′-Methyluridine,"A simple and efficient process to prepare Uprifosbuvir intermediate, 2′-deoxy-α-2′-chloro-β-2′-methyluridine ( 1 ), from bis-pivaloyl tertiary alcohol 5a is described. The key discoveries are a novel BSA-promoted anhydrouridine formation catalyzed by HCl as an additive and a milder safe Me 2 SiCl 2 -promoted chlorination of anhydrouridine. These discoveries collectively enabled the establishment of a robust process toward compound 1, which was demonstrated successfully at the plant scale.",10.1021/acs.oprd.2c00191,2022-08-16,0.5938663874113878
Organic Letters,Concise Synthesis of the <i>Erythrina</i> Alkaloid 3-Demethoxyerythratidinone via Combined Rhodium Catalysis,The total synthesis of the erythrina alkaloid 3-demethoxyerythratidinone has been achieved via a strategy based on combined rhodium catalysis. The catalytic tandem cyclization effected by the interplay of alkynyl and vinylidene rhodium species allows for efficient access to the A and B rings of the tetracyclic erythrinane skeleton in a single step. The synthesis also features rapid preparation of the requisite precursor for the double ring closure and thus has been completed in only 7 total steps in 41% overall yield.,10.1021/ol102535u,2010-11-19,0.5938627712223659
Synthesis,Synthesis and Derivatization of Bis-nor Wieland-Miescher Ketone,"An efficient synthesis of bis-nor Wieland-Miescher ketone and its derivatives starting from commercially available 2-allyl-2-methylcyclopenta-1,3-dione is described.",10.1055/s-2005-916025,2005-01-01,0.5938555824835755
Tetrahedron,An efficient and stereocontrolled synthesis of platelet activating factor from (s)-(−)-malic acid,,10.1016/s0040-4039(00)98901-9,1985-01-01,0.593855057173032
Synthesis,"A New Route to Acridines: Pauson-Khand Reaction on Quinoline-Bearing 1-En-7-ynes Leading to Novel Tetrahydrocyclopenta[<i>c</i>]acridine-2,5-diones","Efficient Pauson-Khand reactions on quinolines bearing 1-en-7-ynes features gave tetrahydrocyclopenta[c]acridine derivatives. The quinoline intermediates were obtained in two steps: a Sonogashira reaction with functionalized alkynes (TMS, Bu, Ph, CHB2OTHP) followed by a Grignard reaction with allylmagnesium bromide. The sequence provides new acridine structures in four high yielding steps from commercially available quinolines.",10.1055/s-2005-870016,2005-01-01,0.5938547208312588
Tetrahedron,"The synthesis of DL-3,3-Difluoroglutamic acid from a 3-oxoprolinol derivative",,10.1016/s0040-4039(00)74045-7,1993-07-01,0.5938541828038364
Tetrahedron,The synthesis of a decarboxylated derivative of the neurotoxin kainic acid,,10.1016/s0040-4039(01)86844-1,1978-01-01,0.5938541828038364
Organic Letters,Benzofurans or Isochromenes via the Ring-Opening Cyclization of Cyclopropene Derivatives with Organolithiums,A new and efficient approach to benzocycles from cyclopropene derivatives is described. Deprotection by organolithiums and subsequent ring-opening cyclization of the related 2-cyclopropenyl phenyl or benzyl acetates generated benzofurans and isochromenes in one pot.,10.1021/ol2032009,2012-01-19,0.5938535055162691
Organic Letters,An Efficient Synthesis Strategy to the Core Structure of 6–5–6–5–6-Membered Epipolythiodiketopiperazines,"A concise route to the core structure 1 of 6-5-6-5-6-membered epipolythiodiketopiperazines is described. The strategy relies on construction of the pyrrolines by double nucleophilic opening of a bis(oxabicyclo[2.2.1]heptene) 2, obtained after bidirectional condensation of N,N'-diacetyldiketopiperazine (4) with aldehyde 3.",10.1021/ol500990f,2014-05-19,0.5938529043094799
Angewandte Chemie International Edition,Catalytic Asymmetric Total Synthesis of (−)‐Galanthamine and (−)‐Lycoramine,"The catalytic asymmetric total syntheses of (-)-galanthamine (1) and (-)-lycoramine (2) have been achieved by using a conceptually new strategy featuring two metal-catalyzed reactions as the key steps. A new method for the construction of 3,4-fused benzofurans has been developed through a palladium-catalyzed intramolecular Larock annulation reaction, which was successfully applied to the construction of the ABD tricyclic skeleton of 1 and 2. To achieve the asymmetric synthesis of 1 and 2, a Sc(III)/N,N'-dioxide complex was used to catalyze the enantioselective conjugate addition of 3-alkyl-substituted benzofuranone to methyl vinyl ketone for the construction of a chiral quaternary carbon center.",10.1002/anie.201411338,2015-04-02,0.5938484473911647
Organic Letters,"Total Synthesis of (±)-Larutienine B and (±)-Melokhanine B, D, E, F, and H","We report a versatile and scalable strategy for the concise syntheses of six C2-spirooxindole alkaloids in 13–15 steps. This synthetic approach features an oxidative aza -Diels–Alder cycloaddition and a retro-Mannich/Mannich reaction to build the tetracyclic ring system alongside a formal Michael addition facilitated by neighboring group participation to install the side chain. Notably, the first total synthesis of larutienine B has been accomplished. The outlined strategy offers a complementary solution for addressing the stereocontrol difficulties in syntheses of eburnane-type alkaloids.",10.1021/acs.orglett.5c03815,2025-10-06,0.5938452843892591
Journal of Organic Chemistry,"A Formal Total Synthesis of (−)-FR901483, Using a Tandem Cationic Aza-Cope Rearrangement/Mannich Cyclization Approach","A formal total synthesis of the immunosuppressant FR901483 has been accomplished. The key step in the synthesis utilizes a tandem cationic aza-Cope rearrangement/Mannich cyclization reaction for accessing the unprecedented bridging tricyclic azaspirane substructure of this compound. The tandem reaction proceeds through a bridgehead iminium ion, a functionality that has rarely been explored in the context of natural product syntheses. Improved stereoselectivity was observed in an aldol reaction when using a Boc-protected amino aldehyde and zinc chloride as an additive. A stereoselective epimerization of the aldehyde-containing stereocenter was achieved with l-phenylalanine upon completion of the Mannich cyclization. Finally, this synthesis is the only one to date that controls the stereochemistry of the oxygen-bearing stereocenters. All other synthetic routes required late stage adjustments to at least one of these stereocenters.",10.1021/jo0483567,2004-12-24,0.5938422663489694
Journal of Organic Chemistry,"Synthesis of Dibarrelane, a Dibicyclo[2.2.2]octane Hydrocarbon","The synthesis of a novel hydrocarbon, dibarrelane, has been accomplished in 11 steps via an intramolecular REDDA reaction of a masked o-benzoquinone, followed by Clemmensen reduction and Barton decarboxylation. The twisted structure of the tetracyclic dibarrelane skeleton was also clarified via X-ray crystallography. Finally, it was proposed that dibarrelane has C2 symmetry rather than C(2v) symmetry.",10.1021/jo5003455,2014-02-24,0.5938344214008571
Organic Letters,Synthesis of Bufadienolide Cinobufagin via Late-Stage Singlet Oxygen Oxidation/Rearrangement Approach,"This manuscript describes a concise synthesis of cinobufagin, a natural steroid of the bufadienolide family, from readily available dehydroepiandrosterone (DHEA), as well as its α5-epimer derived from 3- epi -andosterone. This synthesis features expedient installation of the 17β-pyrone moiety with the 14β,15β-epoxide and the 16β-acetoxy group using a photochemical regioselective singlet oxygen [4 + 2] cycloaddition followed by CoTPP-promoted in situ endoperoxide rearrangement to provide a 14β,16β- bis -epoxide in 64% yield with a 1.6:1 d.r. This β,β- bis -epoxide intermediate was subsequently subjected to a regioselective scandium(III) trifluoromethanesulfonate catalyzed House–Meinwald rearrangement to establish the 17β-configuration. The synthesis of cinobufagin is achieved in 12 steps (LLS) and 7.6% overall yield, and we demonstrate that it could be used as a platform for the subsequent medicinal chemistry exploration of cinobufagin analogs such as cinobufagin 5α-epimer.",10.1021/acs.orglett.4c00625,2024-03-15,0.5938326894817197
Synlett,Construction of the Zaragozic Acids Core Bicycle,"All articles of this category Concise synthesis of the bicyclic core of zaragozic acids has been accomplished by the utilization of (2 S ,3 S )-furylglycerol 7 . The key features are based on the diastereoselective dihydroxylation of enone 8 followed by reduction of ketone 11 to control the stereochemistries at the C4-C6 positions of the target molecule. Addition of lithium trimethylsilylacetylide to aldehyde 20 provided propargyl alcohol 21 , which was further transformed into the bicyclic core 25 , a potent intermediate for the synthesis of zaragozic acids. synthesis - zaragozic acid - squalestatin - furylglycerol 2,8-dioxabicyclo[3.2.1]octane",10.1055/s-1998-1988,1998-12-01,0.5938170667662933
Organic Letters,Bioinspired Total Synthesis of Delitschiapyrone A,"A bioinspired seven-step total synthesis of delitschiapyrone A was accomplished in 32% overall yield from commercially available 4-bromo-3,5-dimethoxybenzoic acid. The key step of the synthesis is an exclusively regioselective and diastereoselective reaction cascade consisting of the Diels-Alder reaction, α-ketol rearrangement, and cyclic hemiacetalization, achieved by simply stirring a heterogeneous mixture of two Diels-Alder substrates (putative biosynthetic intermediates) and water at 35 °C, directly furnishing the pentacyclic natural product in 75% yield.",10.1021/acs.orglett.8b01932,2018-07-13,0.593810352387994
Organic Letters,"Enantioselective Synthesis of Chiral 1,5-Benzodiazepin-2-ones by Pd-Catalyzed Asymmetric Hydrogenation and Reductive Amination","The enantioselective synthesis of chiral 4-substituted 4,5-dihydro-1 H -[1,5]benzodiazepin-2(3 H )-ones via asymmetric hydrogenation catalyzed by the Pd/f-spiroPhos complex in the presence of hydrochloric acid as an additive has been developed, achieving excellent enantioselectivities and high turnover numbers, up to 99% ee and TON = 4600. More significantly, the asymmetric reductive amination of β-keto esters with 1,2-phenylenediamine has also been successfully realized to afford chiral 4-substituted 4,5-dihydro-1 H -[1,5]benzodiazepin-2(3 H )-ones with comparable enantioselectivities of up to 99% ee.",10.1021/acs.orglett.4c02932,2024-10-03,0.5938072199184098
Organic Letters,Synthesis of an Influenza Neuraminidase Inhibitor Intermediate via a Highly Diastereoselective Coupling Reaction,[reaction: see text]. A highly diastereoselective coupling reaction between TBSOP (3) and trityl sulfenimine 4 was developed which provided influenza neuraminidase inhibitor intermediate 7 in 80% yield and >99% de after crystallization. The reaction was shown to be reversible with the high diastereoselectivity resulting from a favorable H-bonding interaction in the major diastereomer.,10.1021/ol017268v,2002-04-03,0.593805649351699
Synlett,Synthesis of 2-Amino-5-arylthiazoles by Palladium-Catalyzed Arylation at the C5 Position with Aryl Iodides,A new synthetic route to afford 2-amino-5-aryl thiazoles has been developed. The starting aminothiazole derivative can be arylated at position 5 with aryl iodides under palladium-catalyzed conditions. Mechanistic studies suggest a proton-abstraction pathway for this transformation.,10.1055/s-2007-992368,2007-11-23,0.5937965656990314
Angewandte Chemie International Edition,"Total Synthesis of (−)‐Reidispongiolide A, an Actin‐Targeting Marine Macrolide","Actin class: A stereoselective synthesis of the microfilament-destabilizing cytotoxic macrolide (−)-reidispongiolide A, isolated from the marine sponge Reidispongia coerulea, uses a convergent aldol-based strategy to construct the 26-membered macrolactone, followed by a coupling with an N-vinylformamide subunit. This constitutes the first synthesis of any member of the reidispongiolide/sphinxolide family.",10.1002/anie.200702178,2007-07-06,0.5937948134447338
Journal of Organic Chemistry,"Enantioselective Synthesis of (−)-Dihydrocodeinone: A Short Formal Synthesis of (−)-Morphine<sup>1</sup><sup>,</sup>","[reaction: see text] The radical cyclization approach to the morphine alkaloids has been applied in an asymmetric synthesis of (-)-dihydrocodeinone. A chiral cyclohexenol (R-32), from the CBS reduction of the enone, is the source of chirality. The first key step, tandem closure in which stereochemistry is controlled by geometric constraints, (-)-15b --> (+)-16, was followed by an unprecedented reductive hydroamination, completing the synthesis of (-)-dihydroisocodeine ((-)-17) in 13 steps from commercially available materials.",10.1021/jo0513008,2005-11-04,0.593791713248312
Organic Letters,Three-Component Coupling via the Squarate Ester Cascade as a Concise Route to the Bioactive Triquinane Sesquiterpene Hypnophilin,"[reaction: see text] A squarate ester cascade is used to provide in one step, via the coupling of three reactants, a highly oxygenated linear triquinane product. The latter is transformed in nine steps into hypnophilin. The access route involves a combination of chlorination, reduction, dehydration, and oxidation maneuvers in the proper sequence.",10.1021/ol0102388,2001-12-14,0.5937916013427511
Tetrahedron,"A direct synthesis of atractylodinol, a potent inhibitor of PRRSV, and its biological evaluation",,10.1016/j.tetlet.2016.10.014,2016-10-11,0.5937898923478246
Organic Process Research & Development,The Preparation of Single Enantiomer 2-Naphthylalanine Derivatives Using Rhodium−Methyl <i>BoPhoz</i>-catalyzed Asymmetric Hydrogenation,"The single enantiomers of 2-naphthylalanine and N - tert -butoxycarbonyl 2-naphthylalanine were prepared from 2-naphthaldehyde. The sequence has been optimized and run on multikilogram scale, with the key step the asymmetric hydrogenation of methyl 2-acetamido-3-(2-naphthyl)propenoate using the rhodium complex of the methyl BoPhoz ligand, which proceeded smoothly at scale with 97.9% ee. Enhancement to >99.5% ee was achieved by crystallization of the methyl 2-amino-3-(2-naphthyl)propanoate methanesulfonic acid addition salt, the product of acidic deacylation of the hydrogenation product. This protocol for enantiomeric purity enhancement appears to be general for these types of amino acid derivatives. Subsequent transformations did not effect the enantiomeric purity, affording the desired products in >99.5% ee.",10.1021/op050026g,2005-05-24,0.5937875411964877
Tetrahedron,Reversal of asymmetric induction in stereoselective strecker synthesis on galactosyl amine as the chiral matrix,,10.1016/s0040-4039(00)80504-3,1988-01-01,0.5937862043517742
Tetrahedron,Regioselective synthesis of the kinamycin ABCD ring system,,10.1016/s0040-4039(00)93989-3,1992-01-01,0.593780634014751
Synlett,Synthesis of Ptaeroxylin (Desoxykarenin): An Unusual Chromone from the Sneezewood Tree<i>Ptaeroxylon obliquum</i>,"The first synthesis of the oxepinochromone ptaeroxylin (also known as desoxykarenin) isolated from the sneezewood tree is described, in which the key steps are a Claisen rearrangement and a ring-closing metathesis to form the seven-membered oxygen heterocyclic ring.",10.1055/s-2008-1078250,2008-08-01,0.5937759195954678
Tetrahedron,"β- and α-lithiaton of methyl β-methoxyacrylate: efficient synthesis of α,γ-substituted methyl tetronates - structure of aspertetronins and gregatins",,10.1016/s0040-4039(00)86743-x,1982-01-01,0.5937709581695753
Synthesis,A Highly Efficient Method for the N-Alkylation of Aminopyrazines: Synthesis of Hydrophilic Red Fluorescent Dyes,"A robust and scalable method was developed for the synthesis of N,N′-dialkylated aminopyrazines by a reductive amination route. These new fluorescent pyrazine analogues were shown to absorb and emit light at relatively long wavelengths (˜50 nm) compared to the corresponding diaminopyrazines. The utility of these compounds was demonstrated by the synthesis of hydrophilic fluorescent probes with potential diagnostic applications.",10.1055/s-0029-1220009,2010-05-20,0.5937692396313529
Angewandte Chemie International Edition,"A Telescoped Route to 2,6‐Disubstituted 2,3,4,5‐Tetrahydropyridines and 2,6‐<i>syn</i>‐Disubstituted Piperidines: Total Synthesis of (−)‐Grandisine G","A grand route to grandisines: A method for the conversion of 6-acyl cyclohexenones into 2,6-disubstituted 2,3,4,5-tetrahydropyridines and, after diastereoselective reduction, 2,6-syn-disubstituted piperidines has been developed. The scope of this process is outlined by the synthesis of cis-2-methoxycarbonylmethyl-6-pentylpiperidine and the first total synthesis of the Elaeocarpus-derived alkaloid (−)-grandisine G (see scheme).",10.1002/anie.201208118,2012-12-12,0.5937656018467211
European Journal of Organic Chemistry,Synthesis of 12‐<i>epi</i>‐Protopanaxadiol and Formal Synthesis of Ginsenoside Chikusetsusaponin‐LT<sub>8</sub>,"In the context of the total synthesis of protopanaxadiol, two strategies were explored. One strategy from an optically active trienic epoxide, possessing a 5‐membered ring, prepared from ( S )‐epoxy‐limonene and ( S )‐epoxyfarnesol, which was submitted to Ti‐(III)‐mediated radical cascade to afford an original tetracyclic structure resulting from a 6‐ endo ‐ trig 6‐ endo ‐ trig 8‐ endo ‐ trig process. A second strategy, starting from a Wieland‐Miescher‐type ketone, using a “ring‐by‐ring” synthesis allowed the synthesis of 12‐ epi ‐protopanaxadiol. In this latter strategy, an efficient sequence of reactions to install the two vicinal C8–C14 quaternary centers involves: i) a Barbier type reaction; ii) an oxidative allylic transposition and iii) a nickel‐catalyzed addition of trimethylaluminium. By using this second strategy, 20‐hydroxydammar‐24‐ene‐3,12‐dione was synthesized which represents a formal synthesis of chikusetsusaponin‐LT 8 , isolated from Panax japonicus .",10.1002/ejoc.201901031,2019-07-29,0.5937548361392685
Organic Letters,Synthesis and Characterization of an <i>N</i>-Acylsulfonamide Inhibitor of Human Asparagine Synthetase,"[structure: see text] The synthesis of N-acylsulfonamide 6, which is an analogue of beta-aspartyl-AMP, is described. This compound appears to be the first and only potent inhibitor of human asparagine synthetase that has been described to date. The N-acylsulfonamide 6 exhibits slow-onset inhibition kinetics, with a K(i) of 728 nM. Preparation and characterization of two additional N-acylsulfonamide analogues has also demonstrated the importance of hydrogen-bonding interactions in the recognition of the AS inhibitor with the enzyme. These observations provide the basis for the discovery of new compounds with application in the treatment of drug-resistant leukemia.",10.1021/ol034212n,2003-05-09,0.5937503203834078
Organic Process Research & Development,Asymmetric Synthesis of an MMP-3 Inhibitor Incorporating a 2-Alkyl Succinate Motif,"An efficient and practical synthesis is presented of the pharmaceutically active MMP-3 inhibitor UK-370,106 ( 1 ) via an olefination/catalytic asymmetric hydrogenation sequence. Commercially available 5-bromo-2-iodotoluene was converted in two steps to the biarylpropanal equivalent ( 11 ), which was reacted with the phosphonosuccinate ( 10 ) to selectively afford the trans- β-substituted itaconate ( 12 ). Catalytic asymmetric hydrogenation of the itaconate ( 12 ) was achieved in good conversion and with 86−96% enantiomeric excess with a range of phosphine-modified rhodium and ruthenium cationic complexes. The resulting enantiomerically enriched 2-alkyl succinate ( 2 ) was elaborated to the desired drug substance ( 1 ) in two steps. The synthesis benefits from several crystalline intermediates, allowing control of process impurities, and can be operated safely within parameters readily achievable on scale. Investigations into the polymorphic forms of ( 1 ) have shown that the compound crystallizes in planar sheets, based on a backbone of hydrogen-bonding amide and acid functionalities, with large hydrophobic pockets formed by the biarylpropyl groups. An understanding of this crystal-packing arrangement has aided the development of crystallization processes allowing complete control over solid form.",10.1021/op034001y,2003-03-22,0.5937440031632153
Tetrahedron,"Improved synthesis of (S)-7-amino-5H,7H-dibenzo[b,d]azepin-6-one, a building block for γ-secretase inhibitors",,10.1016/j.tetlet.2009.08.090,2009-09-02,0.5937390777025169
Organic Letters,Stereoselective Synthesis of a Monocyclic Peloruside A Analogue,"The stereoselective synthesis of the monocyclic peloruside A analogue 4 has been achieved, following a new efficient approach for the introduction of the side chain, involving a late-stage addition of vinyl lithium species 7a to aldehyde 8. Further key steps are a highly diastereoselective allyltitanation reaction and a RCM-based macrocyclization.",10.1021/ol100123p,2010-02-08,0.5937381599029528
Journal of the American Chemical Society,Synthesis of the Eight Enantiomerically Pure Diastereomers of the 12-F<sub>2</sub>-Isoprostanes,Syntheses of the eight enantiomerically pure diastereomers of the 12-F(2)-isoprostanes (4-11) are described. The key steps included rhodium-mediated intramolecular cyclopropanation and enzymatic resolution of the racemic diol 12.,10.1021/ja020816v,2002-10-11,0.5937344266344317
European Journal of Organic Chemistry,"Efficient Ruthenium-Catalysed Synthesis of 3-Hydroxy-1-propen-1-yl Benzoates: En Route to an Improved Isomerization of 2-Propyn-1-ols into α,β-Unsaturated Aldehydes","A two-step ruthenium(II) and acid-catalysed one-pot selective transformation of 2-propyn-1-ols into α,β-unsaturated aldehydes has been developed. The complex [(dppe)Ru(η3-CH2C(Me)CH2)2] (dppe = Ph2PCH2CH2PPh2) is an efficient precatalyst for the anti-Markovnikov addition of benzoic acid to 2-propyn-1-ols with the formation of 3-hydroxy-1-propen-1-yl benzoates in good yields. The latter readily undergo rapid transformation into α,β-unsaturated aldehydes on treatment with a catalytic amount of an acid such as PTSA or HBF4 at room temperature.",10.1002/1099-0690(200007)2000:13<2361::aid-ejoc2361>3.0.co;2-s,2000-07-01,0.593732165574466
Organic Letters,Palladium-Catalyzed Stereoselective Cyclization of <i>in Situ</i> Formed Allenyl Hemiacetals: Synthesis of Rosuvastatin and Pitavastatin,"A diastereoselective palladium-catalyzed cyclization of allenyl hemiacetals is described. It permits the selective synthesis of 1,3-dioxane derivatives, precursors for syn-configured 1,3-diols which make an appearance in all of the statin representatives. The reaction allows the total synthesis of Rosuvastatin and Pitavastatin in a straightforward fashion.",10.1021/acs.orglett.8b01156,2018-05-17,0.5937293756126082
Journal of Organic Chemistry,Asymmetric Total Synthesis of Phosphatidylinositol 3-Phosphate and 4-Phosphate Derivatives,"New asymmetric syntheses of phosphatidylinositol 3-phosphate (PtdIns(3)P) and phosphatidylinositol 4-phosphate (PtdIns(4)P) derivatives are described. Key intermediates were used to prepare diacylglyceryl moieties with dibutyryl, dioctanoyl, and dihexadecanoyl chains. In addition, a modified route provided PtdIns(3)P and PtdIns(4)P triesters with P-1-linked aminopropyl groups for preparation of affinity probes. The synthesis of the inosityl precursor employed a dibutyltin oxide-mediated p -methoxybenzyl (PMB) etherification to give either the 2-PMB- or the 3-PMB-protected glucopyranosides. The Ferrier rearrangement was used to convert suitably protected glucose derivatives to enantiomerically pure, differentially protected d - myo -inositol key intermediates. A versatile phosphoramidite reagent was employed to allow synthesis of PtdInsP n derivatives with diacylglyceryl moieties of different chain lengths.",10.1021/jo980501r,1998-09-01,0.5937257132186159
Journal of the American Chemical Society,A direct synthesis of hydroxysemperoside deglucoside,A 1 0-step synthesis of hydroxysemperoside deglucoside has been achieved. The key step is an organopalladium-mediated cyclization that produces a highly functionalized oxabicyclooctane. The remaining functional groups are introduced by addition to the exo face of the fused bicyclic system.,10.1021/ja00208a012,1989-12-01,0.5937196162652898
Synlett,Chemoenzymatic Formal Total Synthesis of Pancratistatin from Narciclasine-Type Compounds via Myers Transposition: Model Study for a Short Conversion of Narciclasine to Pancratistatin,"A formal total synthesis of pancratistatin was accomplished by conversion of advanced intermediates, used in the synthesis of narciclasine, to pancratistatin precursors via Myers’ reductive transposition as the key strategic step. The synthesis began with the whole cell fermentation of m-dibromobenzene with JM109(pDTG601a), a recombinant strain that over-expresses toluene dioxygenase, which provided the corresponding cis-dihydrodiol 16 as a single isomer with complete optical purity. The key reductive transposition of the allylic alcohol 8a to olefin 9a allowed for further installation of the C-1/C-2 trans-diol, ­required for the pancratistatin scaffold, through the introduction of a cyclic sulfate and its subsequent opening. The formal synthesis of pancratistatin was accomplished in 14 steps (12 operations) from commercially available m-dibromobenzene. Experimental and spectral data are provided for all new compounds.",10.1055/s-0036-1588515,2017-08-03,0.5937153954102528
Tetrahedron,"A novel deaminative cyclization of aminoglycoside. Synthesis of a kanamycin B variant having 2-oxa-5-azabicyclo[2,2,2]oct-1,5-diene ring",,10.1016/s0040-4039(00)97539-7,1982-01-01,0.5937145128594513
Synthesis,"A Highly Stereoselective Synthesis of a New Propargylic Epoxide: (3<i>R</i>,4<i>S</i>)-1-<i>tert</i>-Butyldimethylsilyl-3,4-epoxy-1-pentyne","All articles of this category The synthesis of a novel enantiopure propargylic epoxide, (3 R , 4 S )-1- tert -butyldimethylsilyl-3,4-epoxy-1-pentyne (9) , from a readily available tartaric acid derivative, (4 R ,5 S )-5-{[( tert -butyldimethyl-silyl)oxy]methyl}-2,2-dimethyl-1, 3-dioxalane-4-carbaldehyde (1) , is described.",10.1055/s-1993-25806,1993-01-01,0.5937123805788452
Synthesis,"1-Nicotinoylbenzotriazole: A Convenient Tool for Site-Selective Protection of 5,7-Dihydroxycoumarins","1-Nicotinoylbenzotriazole (NicBt) was uncovered as an efficient protecting agent for the site-selective acylation of resorcinol-type phenolic groups with almost equal reactivity. The use of NicBt allows selective protection of the 7-OH group in 5,7-dihydroxycoumarins in one simple scalable step, while combination of the nicotinoylation with tosylation–denicotinoylation or silylation–denicotinoylation yields 5-OH-protected 5,7-dihydroxycoumarins. Furthermore, nicotinoylated 5,7-dihydroxycoumarins proved useful in a gram-scale three-step preparation of a 2,2-dimethylpyrano[2,3-f]coumarin, a key intermediate for the synthesis of calanolide A, an HIV reverse transcriptase and Mycobacterium tuberculosis inhibitor, and its active analogues.",10.1055/s-0039-1690104,2019-06-26,0.5936973757553905
Journal of Organic Chemistry,"Synthesis of Symmetric 1,4-Diamino-2-Butynes via a Cu(I)-Catalyzed One-Pot A<sup>3</sup>-Coupling/Decarboxylative Coupling of a Propiolic Acid, an Aldehyde, and an Amine","A novel microwave-assisted approach for the one-pot Cu(I)-catalyzed A(3)-coupling/decarboxylative coupling (PA(2)-coupling) of a propiolic acid, an aldehyde, and an amine, resulting in the formation of diversely substituted 1,4-diamino-2-butynes,is described. It is noteworthy that this new multicomponent coupling provides an efficient access to introduce alkyl and aryl group at the 1,4-position of the 1,4-diamino-2-butynes.",10.1021/jo300562j,2012-05-08,0.5936965576134056
Tetrahedron,"A new efficient method for the synthesis of 3,4-dihydro-2H-1,4-benzoxazines via iodocyclization",,10.1016/j.tetlet.2010.08.016,2010-08-12,0.5936866471854294
Organic Letters,Stereoselective Total Synthesis of (−)-Perrottetinene and Assignment of Its Absolute Configuration,"The first stereoselective total synthesis of the bibenzyl tetrahydrocannabinol, (-)-perrottetinene, has been achieved from readily available starting materials. The absolute stereochemistry is derived from a chiral gamma-hydroxy vinylstannane. The key reaction is the synthesis of the cis-disubstituted cyclohexene ring of perrottetinene by diastereoselective Ireland-Claisen rearrangement and a ring-closing metathesis reaction. The absolute configuration of (-)-perrottetinene is proposed.",10.1021/ol702692q,2007-12-18,0.5936810402543164
Journal of Organic Chemistry,Novel Synthesis of Bis(phosphonic acid)−Steroid Conjugates,"An efficient synthesis has been realized for several members of a new class of potential bone resorption inhibitors consisting of steroidal oestrogenic units linked at the 3 and 17 positions to a geminal bisphosphonate moiety through an ester linkage of variable length. The convergent synthesis utilizes benzyl bisphosphonates, transesterification, and Meldrum's acid chemistry and has the potential to allow many oestrogenic derivatives as well as other biologically active compounds to be coupled to the geminal bisphosphonate moeity.",10.1021/jo001489h,2001-05-05,0.5936741409558561
Organic Letters,Modular Asymmetric Synthesis of Functionalized Azaspirocycles Based on the Sulfoximine Auxiliary,"A modular asymmetric synthesis of the functionalized azaspirocycles 6 (m = 2, n = 1), 7 (m = 1, n = 2), 8 (m = n = 2), 12, 20, and 24 from the cyclic allylic sulfoximines 1 is described. The synthetic strategy is based on the stereoselective construction of the carbocycle 4 containing the amino-substituted tertiary C atom from 1 followed by the generation of the azaspirocycle. Three different routes have been followed for the synthesis of the heterocyclic ring: N,C-dianion cycloalkylation, ring-closing metathesis, and N-acyl iminium ion formation.",10.1021/ol0706410,2007-05-01,0.5936725494939038
Organic Letters,A Convergent Strategy for the Synthesis of Polycyclic Ethers by Using Oxiranyl Anions,"A new [X+2+Y]-type for the convergent synthesis of polycyclic ethers based on an oxiranyl anion strategy was developed. The sequence involves nucleophilic substitution of a triflate with an oxiranyl anion followed by 6-endo cyclization, ring expansion, and reductive etherification. The protocol features a flexible approach toward trans-fused polycyclic arrays consisting of six- and seven-membered ether rings from the same starting materials.",10.1021/ol202467z,2011-10-06,0.5936706668232469
Organic Letters,Asymmetric Cyclopentannelation. Chiral Auxiliary on the Allene,"An enantioselective variant of the synthesis of cross-conjugated cyclopentenones, based on D-glucose-derived chiral auxiliaries, is described. Minor modification of the method makes it applicable to the preparation of both enantiomeric series of products. Both enantiomers of the key intermediate in our roseophilin synthesis have been prepared.",10.1021/ol0001362,2000-07-08,0.59367035205276
Synthesis,Approach to the Eleutherobin Core: Synthesis of a Key Intermediate by Intramolecular Diels-Alder Cycloaddition,"An attractive intermediate in the total synthesis of the eleutherobin core has been obtained. Both syn and anti aldol diastereoisomers were synthesized by two different diastereoselective reaction sequences from 5-methyl-4-(pyrrolydin-1'-yl)-5H-furan-2-one. Each diastereoisomer was esterified and subjected to an intramolecular Diels-Alder reaction, which led to an intermediate that possesses rings A and C of the eleutherobin skeleton.",10.1055/s-2006-926456,2006-05-01,0.5936680855509533
Tetrahedron,Novel one pot synthesis of 2-amino-4-chloroquinolines via Smiles rearrangement,,10.1016/j.tetlet.2012.04.028,2012-04-21,0.5936621295049355
Tetrahedron,A new synthetic route to the fungal sex hormone antheridiol and the determination of its absolute stereochemistry,,10.1016/s0040-4039(01)84440-3,1972-02-01,0.5936600972996503
Journal of Organic Chemistry,A Study of an 8-Aminoquinoline-Directed C(sp<sup>2</sup>)–H Arylation Reaction on the Route to Chiral Cyclobutane Keto Acids from Myrtenal,"High Resolution Image Download MS PowerPoint Slide This work outlines a synthetic route that can be used to access chiral cyclobutane keto acids with two stereocenters in five steps from the inexpensive terpene myrtenal. Furthermore, the developed route includes an 8-aminoquinoline-directed C(sp 2 )–H arylation as one of its key steps, which allows a wide range of aryl and heteroaryl groups to be incorporated into the bicyclic myrtenal scaffold prior to the ozonolysis-based ring-opening step that furnishes the target cyclobutane keto acids. This synthetic route is expected to find many applications connected to the synthesis of natural product-like compounds and small molecule libraries.",10.1021/acs.joc.1c00774,2021-05-27,0.5936590082155407
Tetrahedron,A synthetic approach to the phorboxazoles—synthesis of the exocyclic fragment,,10.1016/j.tetlet.2016.08.090,2016-09-06,0.5936566076030904
Tetrahedron,"Efficient strategy for the stereoselective synthesis of 2,3-disubstituted benzo[α]quinolizidine alkaloids: concise synthesis of (−)-protoemetinol",,10.1016/j.tetlet.2014.12.030,2014-12-13,0.5936559991799009
Tetrahedron,New coumarins from Harbouria trachypleura: isolation and synthesis,,10.1016/s0040-4039(01)01355-7,2001-09-01,0.5936504050221078
Tetrahedron,Isolation and synthesis of siphonarienal a new polypropionate from Siphonaria grisea,,10.1016/s0040-4039(00)76923-1,1994-05-01,0.5936504050221078
Tetrahedron,Extractives of Thailand cannabis: Synthesis of canniprene and isolation of new geranylated and prenylated chrysoeriols,,10.1016/0040-4039(80)80248-6,1980-01-01,0.5936504050221078
Synthesis,The Total Synthesis of Antrimycin D<sub>v</sub>; III:<sup>1</sup>Construction of the Protected Hexapeptide and Deprotection,All articles of this category In the preceding communication we described the synthesis of tetrahydropyridazine-3-carboxylic acids and their incorporation into peptides. We have also prepared the tripeptide 2 which is contained in the antibiotic antrimycin D v 15 . We now report on the preparation of the building blocks 1 and 4 and their coupling with 2 to give the protected antrimycin D v 14 . The deprotection of this heptapeptide constitutes the total synthesis of antrimycin D v .,10.1055/s-1993-25948,1993-01-01,0.5936501036700518
Journal of Organic Chemistry,Highly Stereoselective Synthesis of <i>an</i><i>ti</i>-N-Protected-α-Amino Epoxides,"A simple and efficient method for the synthesis of anti-N-protected amino epoxides from carbamate-protected amino acids is described. The two key steps are the monobromination of a beta-ketoester and chelation-controlled reduction of a bromomethyl ketone intermediate. Good overall yields, high diastereoselectivity, and excellent functional group compatibility are characteristic.",10.1021/jo010319h,2001-08-01,0.5936467161983927
Journal of Organic Chemistry,Stereocontrolled Synthesis of (−)-Kainic Acid from <i>trans-</i>4-Hydroxy-<scp>l</scp>-proline<sup>†</sup>,[reaction: see text] A highly stereoselective synthesis of (-)-kainic acid has been achieved in 14 steps and >7% overall yield starting from inexpensive trans-4-hydroxy-L-proline. The key steps are diastereoselective enolate alkylation and cuprate substitution reactions.,10.1021/jo051508t,2005-11-18,0.5936463515706961
Journal of the American Chemical Society,Total Synthesis of the Maduropeptin Chromophore Aglycon,"Maduropeptin consists of a 1:1 complex of a carrier protein and a chromophore. The maduropeptin chromophore exhibits potent antitumor and antibacterial activities by means of a mechanism distinct from that of structurally related natural enediynes. The nine-membered enediyne forms after nucleophilic attack of the C14-amide nitrogen and then cycloaromatizes spontaneously to form the p -benzyne biradical, which can efficiently cleave double-stranded DNA by hydrogen abstraction. Thus, the chromophore represents a stable prodrug form of the highly reactive enediyne structure. In this paper, we report the first total synthesis of the aglycon 1 of the chromophore. The bicyclo[7.3.0]enediyne core with the exo -C4,13- Z -olefin and the 15-membered ansa-macrolactam with the non-biaryl atropisomerism are unique structural features that made this synthesis particularly challenging. The key reactions used in the described synthesis were cerium amide promoted nine-membered ring formation, one-pot macrolactam formation from the azide pentafluorophenyl ester, and SmI 2 -mediated reductive 1,2-elimination to construct the C13-Z-olefin.",10.1021/ja076671f,2007-10-23,0.5936447703555678
Tetrahedron,Synthesis of a norcubane derivative,,10.1016/s0040-4039(00)71974-5,1975-01-01,0.5936325401548826
Tetrahedron,The synthesis of a taondiol derivative,,10.1016/s0040-4039(01)84821-8,1972-01-01,0.5936325401548826
Tetrahedron,Synthesis of a partially benzylated derivative of the anhydro-d-altro-heptulose found in Coriaria japonica A,,10.1016/j.tetlet.2007.06.057,2007-06-20,0.5936325401548826
Tetrahedron,Synthesis of Amphiphilic Chitoheptaose Derivative,,10.1016/s0040-4039(97)10104-6,1997-11-01,0.5936325401548826
Tetrahedron,Synthesis of a 4β-carboxyethyl derivative of thienamycin,,10.1016/s0040-4039(00)76942-5,1994-07-01,0.5936325401548826
Tetrahedron,Synthesis of (4.5.5.5]fenestrane and a [4.4.5.5]fenestrane derivative,,10.1016/s0040-4039(00)86928-2,1982-01-01,0.5936325401548826
Tetrahedron,First synthesis of parazoanthine-A and its O-Me derivative,,10.1016/j.tetlet.2012.10.066,2012-10-24,0.5936325401548826
Tetrahedron,A synthesis of a derivative of pillarose,,10.1016/s0040-4039(01)94490-9,1978-01-01,0.5936325401548826
Tetrahedron,Synthesis of a trimetallocene derivative,,10.1016/s0040-4039(00)71747-3,1961-01-01,0.5936325401548826
Tetrahedron,Synthesis of a capped dicationic derivative of β-cyclodextrin,,10.1016/s0040-4039(99)00353-6,1999-04-01,0.5936325401548826
Tetrahedron,"Synthesis of “α-Homogalactostatin” and of its 1,N-anhydro derivative",,10.1016/0040-4039(95)00708-k,1995-06-01,0.5936325401548826
Tetrahedron,"Synthesis of 9-oxa-noradamantane derivative, an aesthetically pleasing ‘oxa-basket’",,10.1016/j.tetlet.2009.07.143,2009-08-04,0.5936325401548826
Tetrahedron,Synthesis of azonia derivative of hexahelicene,,10.1016/s0040-4039(01)93938-3,1989-01-01,0.5936325401548826
Tetrahedron,Synthesis of an oxabicyclo[7.2.1] enediyne from a furanoside derivative,,10.1016/s0040-4039(00)60810-9,1992-01-01,0.5936325401548826
Tetrahedron,Synthesis of homoharringtonine and its derivative .,,10.1016/s0040-4039(00)87634-0,1982-01-01,0.5936325401548826
Synlett,Synthesis of Spirastrellolide A Fragments for Structure Elucidation,A stereocontrolled synthesis of two diastereomeric C1-C22 fragments of spirastrellolide A consistent with reported spectroscopic data has been achieved to aid in a complete configurational assignment of this structurally novel and potent antimitotic natural product. A highly convergent coupling of two enantiomeric C1-C10 methyl ketone fragments with an enantiopure C11-C22 spiroketal ­aldehyde produced the C1-C22 fragments with a longest linear sequence of 13 steps from commercially available starting materials.,10.1055/s-2006-933144,2006-03-14,0.5936271660146226
Organic Process Research & Development,Utilization of ReactIR in Fit for Purpose Process Enablement,"An efficient four-step synthesis of 1 is described in which utilization of ReactIR was key to efficient processing and reaction monitoring. Key chemical steps included (i) nucleophilic aromatic substitution, iron reduction of aromatic nitro group to aniline, (ii) decarboxylation, and (iii) ester formation.",10.1021/op5003165,2014-12-06,0.5936266270186794
Organic Letters,Total Synthesis of (+)-Mycalamide A,"A convergent total synthesis of (+)-mycalamide A is described. A Yb(OTf)3-TMSCl catalytic system is used to synthesize a trioxadecalin ring system, which contains the right segment of mycalamide A. In addition, a tetrahydropyran ring, which is the left segment, is constructed with use of a novel one-pot delta-lactonization protocol. Both segments are prepared from a common starting material, d-mannitol. These segments are then coupled and the functional groups are transformed to synthesize (+)-mycalamide A.",10.1021/ol052943c,2006-02-01,0.5936228004776983
Organic Process Research & Development,Fit-for-Purpose Synthesis of an Aza-Cryptophycin Analogue as the Payload for an Antibody–Drug Conjugate,"The synthesis of an aza-cryptophycin analogue is described, featuring a highly trans-selective ring-closing metathesis reaction and an asymmetric Corey–Chaykovsky-type reaction to install the epoxide function. This latter reaction is an answer to the long-standing synthetic challenged posed by the efficient formation of the epoxide function of the cryptophycin family of compounds in a diastereoselective manner. It allows for a one-third reduction in the number of steps compared with the previously used synthesis (27 to 19 steps) and increases the overall yield of the longest linear sequence by a factor of 27 (0.6% to 16%). This fit-for-purpose synthesis allowed the production of a steady supply of the material for the early phase of a cryptophycin-based antibody–drug conjugate program.",10.1021/acs.oprd.2c00080,2022-05-10,0.5936222447430288
Green Chemistry,"Organocatalyzed carboxylative cyclization of propargylic amides with atmospheric CO <sub>2</sub> towards oxazolidine-2,4-diones","A facile and practical TBD-catalyzed carboxylative cyclization of propargylic amides with atmospheric CO <sub>2</sub> has been developed for the formation of ( <italic>Z</italic> ) 5-alkylidene 1,3-oxazolidine-2,4-diones.",10.1039/c8gc03929a,2019-01-01,0.593621703574406
Organic Process Research & Development,Second-Generation Process Research Towards Eletriptan: A Fischer Indole Approach,"The development of a second-generation process for the synthesis of eletriptan via a Fischer indole cyclisation is described. The finalised process offers several potential advantages over the current route of manufacture including cost, throughput, and safety.",10.1021/op100251q,2010-12-01,0.5936211166740762
European Journal of Organic Chemistry,Synthesis of Easy‐to‐Functionalize Azabicycloalkane Scaffolds as Dipeptide Turn Mimics en Route to cRGD‐Based Bioconjugates,"Abstract In this paper we report the synthesis of new azabicycloalkane scaffolds, which could be exploited to obtain cRGD‐based bioconjugates that may find promising application for targeted drug delivery, theranostic, and general cancer‐cell labeling. By exploiting a Hosomi–Sakurai intramolecular allylation reaction we efficiently converted a silylated aldehyde precursor into 7,5‐fused lactam scaffolds endowed with an exocyclic double bond. The presence of the vinyl function should make it possible to conjugate bioactive compounds to selectively carry them to tumor sites. The optimized synthetic sequence allows the gram‐scale preparation of the target scaffolds in a few steps and good 39 % overall yield from readily accessible materials. The high reactivity of the exocyclic olefin moiety was ascertained by performing a Heck coupling reaction with 1‐bromo‐4‐nitrobenzene, which gave the corresponding functionalized derivatives in good (80–91 %) yields.",10.1002/ejoc.201501003,2015-10-23,0.5936112055421587
Synlett,Palladium(II)-Catalyzed Dehydrative Cyclization of cis-4-Alkylcycloalken-2-ols. Synthesis of Tricyclic Spiroketals in a One-Pot Sequence,"All articles of this category An efficient one-pot process involving palladium-catalyzed dehydrative cyclization, hydroxyl group deprotection and spiroketalization is described and offers an easy access to the tricyclic spiroketal framework of phyllanthocin. Tetrahydrobenzofurans - spiroketals - palladium catalyst - heterocyclization - diastereoselective - C-O bond formation",10.1055/s-1996-5481,1996-06-01,0.593609250812593
Organic Letters,Dearomative Access to (−)-Thebaine and Derivatives,"A synthesis of the natural product thebaine is reported in eight steps from commercially available starting materials, hinging on the dearomatization and coupling of simple aromatic starting materials. This provides divergent access to two unnatural opioid derivatives and is aimed at the long-term development of synthetic opioid analogs of the ""wonderdrug"" Naloxone. Additionally, a formal enantioselective synthesis of all reported targets is disclosed that leverages a catalytic asymmetric dearomatization via anion-pairing catalysis.",10.1021/acs.orglett.3c03270,2023-11-17,0.5936046710429956
Tetrahedron,Dienamines as diels-alder dienes. An efficient synthesis of a key intermediate for drimane-related sesquiterpenes,,10.1016/s0040-4039(01)91180-3,1984-01-01,0.5935961291185751
Synthesis,An Improved and Alternative Method for the Preparation of Per(6-bromo-6-deoxy)cyclodextrins,"A practical and efficient approach to the regioselective synthesis of per(6-bromo-6-deoxy)cyclodextrins is described. The method utilizes the easily accessible (chloro(phenylthio) methylene) dimethylammonium chloride (CPMA), circumventing disadvantages of earlier protocols.",10.1055/s-0030-1260241,2011-09-26,0.5935958407713766
Synlett,Addition of Organolithiums to the (<i>R</i>)-<i>O</i>-(1-Phenylbutyl)hydroxylamine (ROPH<sub>y</sub>) Oxime of Cinnamaldehyde. Asymmetric Synthesis of α-Aminoacids,All articles of this category A new asymmetric synthesis of α-aminoacids is described in which the key step is the diastereoselective addition of organolithium reagents to ( R )- O -(1-phenylbutyl) cinnamaldoxime. oxime ether - diastereoselective addition - hydroxylamine - aminoacid,10.1055/s-1997-3252,1997-06-01,0.5935911537035291
Tetrahedron,Unprecedented SnCl2·2H2O-mediated intramolecular cyclization of nitroarenes via C–N bond formation: a new entry to the synthesis of cryptotackieine and related skeletons,,10.1016/j.tetlet.2008.09.154,2008-10-02,0.5935843348808131
Organic Letters,Unified Enantioselective Synthesis of 5-Phenylmorphans and <i>cis</i> -Octahydroisoquinolines,"Modifications of morphine have delivered novel opioid scaffolds, such as 5-phenylmorphans and cis -octahydroisoquinolines, that exhibit various pharmacological profiles. To date, these substructures have only been prepared using chiral resolution strategies that require purging of 50% of the material at a late stage of a synthesis. Herein, we disclose the first enantioselective synthesis of both scaffolds. This unified synthesis exploits an enantioselective conjugate addition, followed by conversion of the ester to a common amine intermediate. Subsequently, a diastereoselective aza-Michael reaction generates 5-phenylmorphans, while a γ-regioselective and diastereoselective Mannich reaction generates cis -octahydroisoquinolines.",10.1021/acs.orglett.5c02600,2025-08-01,0.5935810528414014
Synthesis,"Convergent Synthesis of 1,1′-Biisoquinolines Tethered to Calamitic Subunits","A convergent synthesis of a series of 4,4′-functionalized 1,1′-biisoquinolines via 1-chloro-4-hydroxyisoquinoline and substituted biphenyl- and phenylpyrimidine ethers as building blocks is described. The latter were prepared by Williamson etherification of the respective 4-hydroxybiphenyl and -phenylpyrimidine precursors with dibromoalkanes, allowing variation of the spacer lengths. 1-Chloro-4-hydroxyisoquinoline was obtained from N-phthalimidoglycine ethyl ester through a Gabriel-Colman reaction as a key step. Linkage of the building blocks by etherification in the presence of potassium carbonate gave the isoquinolines, which were submitted to a nickel(II) chloride mediated homocoupling to yield the ligand systems.",10.1055/s-2008-1067184,2008-07-18,0.5935788306042147
Organic Letters,"Synthesis of Prostaglandin Analogues, Latanoprost and Bimatoprost, Using Organocatalysis via a Key Bicyclic Enal Intermediate","Two antiglaucoma drugs, bimatoprost and latanoprost, which are analogues of the prostaglandin, PGF2α, have been synthesized in just 7 and 8 steps, respectively. The syntheses employ an organocatalytic aldol reaction that converts succinaldehyde into a key bicyclic enal intermediate, which is primed for attachment of the required lower and upper side chains. By utilizing the crystalline lactone, the drug molecules were prepared in >99% ee.",10.1021/ol503520f,2015-01-12,0.5935785857452657
Angewandte Chemie International Edition,Total Synthesis of the Diterpene Waihoensene,"A racemic and scalable enantioselective total synthesis of (+)-waihoensene was accomplished. (+)-Waihoensene belongs to the diterpene natural product family, and it features an angular triquinane substructure motif. Its tetracyclic [6.5.5.5]backbone is all-cis-fused, containing six contiguous stereocenters, four of which are quaternary. These structural features were efficiently installed by means of a diastereoselective radical cyclization, followed by an intramolecular Pauson-Khand reaction, a diastereoselective α-alkylation, and a diastereoselective 1,4-addition reaction. Enantioselectivity was introduced at an early stage, by an asymmetric palladium catalyzed decarboxylative allylation reaction on gram scale.",10.1002/anie.202011298,2020-10-26,0.5935741082726438
Synlett,Preparation of a Spiroisoxazolinopiperidinylbenzamide-Based Scaffold,"A route to spiroisoxazolinopiperidinylbenzamides has been developed. N-Boc-4-piperidone underwent a Wittig olefination and Boc-deprotection followed by a nucleophilic substitution reaction with 4-fluoro-3-nitrobenzoic acid to yield the starting scaffold 3 in excellent yields. Diversification of the acid with primary amines, followed nitrile oxide formation in situ (aryl oximes treated with bleach) and subsequent 1,3-dipolar cycloaddition to the exo­methylene moiety delivered the spiroisoxazolinopiperdines. Reduction of the arylnitro group followed by acylation with acid chlorides or reductive amination with aldehydes yielded the spiroisoxazolinopiperidinylbenzamide library.",10.1055/s-0029-1218290,2009-10-13,0.5935702503968909
Tetrahedron,Palladium (O) mediated β-carboline synthesis: Preparation of the CDE ring system of lavendamycin,,10.1016/s0040-4039(01)91001-9,1984-01-01,0.593561250256823
Journal of Organic Chemistry,Total Synthesis of Adunctin B,"Total synthesis of (±)-adunctin B, a natural product isolated from Piper aduncum (Piperaceae), has been achieved using two different strategies, in seven and three steps. The efficient approach features highly atom economical and diastereoselective Friedel-Crafts acylation, alkylation reaction and palladium catalyzed Wacker type oxidative cyclization.",10.1021/acs.joc.8b00015,2018-02-20,0.5935550947999048
Synthesis,Expeditious Synthesis of Papilionaceous Molecules Containing Oligobenzofurans,"An efficient synthetic route to construct particular papilionaceous molecules containing oligobenzofurans is described. The key steps involved composing the backbone of the molecules by the Sonogashira cross-coupling reaction, followed by closing the benzofuran ring under alkaline conditions, and further aromatic cyclization of a multi-benzofuranyl precursor using ferric chloride as the oxidative reagent. Basic optical studies (UV-Vis, fluorescence, and fluorescence quantum yield) have been carried out on the synthesized molecules.",10.1055/s-0031-1290066,2012-01-16,0.5935537010499072
Tetrahedron,"Terpestacin, a novel syncytium formation inhibitor, isolated from Arthrinium species",,10.1016/0040-4039(93)85110-i,1993-01-01,0.5935530638643949
Synlett,"A New Synthesis of (R)- and (S)-Mevalonolactone from the Enzymatic Resolution of (R,S)-2-(3-Methyl-2-butenyl)-oxiranemethanoI",All articles of this category A new chemoenzymatic synthesis of both enantiomers of mevalonolactone 1 starting from the Pseudomonas fluorescens lipasecatalyzed resolution of racemic 2-(3-methyl-2-butenyl)-oxiranemethanol 2 is reported.,10.1055/s-1994-22998,1994-01-01,0.5935512199801262
Angewandte Chemie International Edition,Total Synthesis of (±)‐Platencin,"Resistant bacteria—beware! Platencin, a structurally novel broad-spectrum antibacterial agent, was the target of a total synthesis from o-anisic acid (see scheme). A Diels–Alder reaction with an α-substituted cyclohexenone as well as a [Ni(cod)2]-promoted 1,4-addition enables the concise and stereocontrolled formation of the core. A protecting group free coupling with an aniline unit completed the synthesis. cod=1,5-cyclooctadiene.",10.1002/anie.200800756,2008-05-04,0.5935479586841801
Tetrahedron,p-Toluenesulfonic acid-mediated cyclization of o-(1-alkynyl)anisoles or thioanisoles: synthesis of 2-arylsubstituted benzofurans and benzothiophenes,,10.1016/j.tetlet.2009.03.087,2009-03-17,0.5935447263790289
Synlett,Highly Selective Synthesis of Polyfunctionalized Carbo- and Heterocycles Based on Ring Expansion of Squaric Acid Derivatives,,10.1055/s-1998-5893,1998-11-01,0.5935439930769673
Journal of Organic Chemistry,Synthesis of (−)-Tetrodotoxin:  Preparation of an Advanced Cyclohexenone Intermediate,"The preparation of an advanced intermediate toward the enantioselective synthesis of tetrodotoxin is outlined. The enantiomerically pure cyclopentene 15 was generated from ketone 14 by alkylidene carbene insertion with retention of absolute configuration. An ozonolysis/aldol sequence first produced the trans cyclohexenone, which upon epimerization gave the more stable cis enone 18.",10.1021/jo0301189,2003-09-11,0.593522292787443
Synlett,Total Synthesis of (+)-Aculeatin D and (+)-6-epi-Aculeatin D,The stereoselective total synthesis of spiroketal natural product (+)-aculeatin D and unnatural (+)-6-epi-aculeatin D has been accomplished. Sharpless kinetic resolution of secondary allylic alcohol and phenyliodine(III) bis(trifluoroacetate) (PIFA)-mediated oxidative spirocyclization were used as key steps in this synthesis.,10.1055/s-0029-1218546,2009-12-09,0.5935181235793113
Angewandte Chemie International Edition,Synthesis and Structure of a Linearly Anti Fused Tetracyclic Undecane. A Potential Intermediate in a Coriolin Synthesis,,10.1002/anie.198310530,1983-09-01,0.5935172794932054
Tetrahedron,Synthesis of chiral succinates via Pd(0) catalyzed carbonylation/asymmetric hydrogenation sequence,,10.1016/s0040-4039(00)75976-4,1994-01-01,0.5935109875203385
Synthesis,"A Novel One Step Synthesis of Pyrazolo[1,5-<i>a</i>]pyridine Derivatives","All articles of this category A Novel one step synthesis of pyrazolo[1,5- a ]pyridines has been developed by condensation of N -amino-3-cyano-4,6-dimethyl-2(1 H )-pyridone ( 1 ) with compounds containing acetyl or active methylene group in presence of anhydrous zinc chloride in refluxing dimethylformamide.",10.1055/s-1987-27976,1987-01-01,0.5934966945482814
Organic Letters,Synthetic Study toward the Total Synthesis of Maoecrystal V,"A novel and concise approach for the construction of the core structure of maoecrystal V (1) has been developed. Utilizing the lead-mediated arylation of beta-ketoesters and oxidative dearomatization/IMDA reaction as key steps, the two consecutive all-carbon quaternary centers (C-9 and C-10) were constructed in a stereoselective manner. The developed chemistry paves the way for the total synthesis of this fascinating natural product.",10.1021/ol9014392,2009-07-16,0.5934951974455114
Journal of Organic Chemistry,"A General Approach to (5<i>S</i>,6<i>R</i>)-6-Alkyl-5-benzyloxy-2-piperidinones:  Application to the Asymmetric Syntheses of Neurokinin Substance P Receptor Antagonist (−)-L-733,061 and (−)-Deoxocassine","A general approach to (5S,6R)-6-alkyl-5-benzyloxy-2-piperidinones based on the regio- and diastereoselective reductive alkylation of (S)-3-benzyloxyglutarimide 7 is described. This method opens an entrance to chiral nonracemic substituted 3-piperidinols. The versatility of the method is illustrated by the asymmetric syntheses of neurokinin substance P receptor antagonist L-733,061 (ent-1), (-)-deoxocassine (4), and an inhibitor of HIV proteases (5a).",10.1021/jo049166z,2004-07-31,0.5934916489747044
Organic Letters,Validating an Endoperoxide as a Key Intermediate in the Biosynthesis of Elysiapyrones,"Compounds 1-3 isolated from Elysia diomedea are described. Compound 1 is an endoperoxide derivative of elysiapyrone A. The biomimetic-type transformation of compound 1 to elysiapyrone A catalyzed by neutral base transformed the endoperoxide to a vicinal diepoxide, thus suggesting the endoperoxide as a key intermediate in the biosynthesis of elysiapyrone A. A biogenetic pathway for their formation involving a cycloaddition of singlet oxygen to a polypropionate alkenyl open chain is proposed.",10.1021/ol8010425,2008-06-24,0.5934900367500867
Organic Letters,"Enantioselective Syntheses of Cryptocarya Triacetate, Cryptocaryolone, and Cryptocaryolone Diacetate","[reaction: see text] The enantioselective syntheses of three natural products from Cryptocarya latifolia have been achieved in 13-15 steps from ethyl sorbate. The route relies upon an enantio- and regioselective Sharpless dihydroxylation and a palladium-catalyzed reduction to establish the absolute stereochemistry. The route also relies upon a highly (E)-selective olefin cross-metathesis reaction to form trans-delta-hydroxy-1-enoates. The resulting delta-hydroxy-1-enoates were subsequently converted into cryptocarya triacetate, cryptocaryolone, and cryptocaryolone diacetate.",10.1021/ol0345529,2003-05-01,0.5934838097230932
Journal of Organic Chemistry,Chemoenzymatic Synthesis of Amaryllidaceae Constituents and Biological Evaluation of their C-1 Analogues. The Next Generation Synthesis of 7-Deoxypancratistatin and <i>trans</i>-Dihydrolycoricidine,"An efficient synthesis of C-1 derivatives of 7-deoxypancratistatin is reported. The key steps include the following: selective opening of an epoxide with aluminum acetylide in the presence of an aziridine; solid-state silica-gel-catalyzed opening of an aziridine; and oxidative cleavage of a phenanthrene core and its recyclization to phenanthridone to provide the key C-1 aldehyde 22. The conversion of this aldehyde to C-1 acetoxymethyl and C-1 hydroxymethyl derivatives is described along with the evaluation of their biological activity against several cancer cell lines and in an apoptosis study. The C-1 acetoxymethyl derivative has shown promising activity comparable to that of the natural product. In addition, a total synthesis of trans-dihydrolycoricidine and a formal total synthesis of 7-deoxypancratistatin are reported from aldehyde 22. Detailed experimental and spectral data are provided for all new compounds.",10.1021/jo1003136,2010-04-07,0.593478365908213
Synlett,Synthesis of Enantiomerically Pure Cyclopentene Building Blocks,"An efficient synthesis of the enantiomerically pure cis-annulated cyclopentenes 2 and ent-2 was established by the use of an enzymatic transesterification and hydrolysis, respectively, followed by an S(N)2-type Substitution with a benzyloxymethyl cuprate and a sigmatropic rearrangement. The advantage of this approach is the short sequence combined with an excellent overall yield and an enantiomeric excess of 99%.",10.1055/s-2007-967937,2007-02-01,0.5934738811254193
Organic Process Research & Development,"Practical Kilogram Synthesis of (<i>S</i>)-1-Benzyl-4-Bromo-3-Methyl-1,2,3,6-Tetrahydropyridine","Despite chiral piperidines being a commonly found motif in approved drugs and drug candidates, the synthesis of these compounds occasionally suffers from challenges of scalability and stereochemical control. As part of a medicinal chemistry program, we sought access to a series of stereochemically pure 3,4-disubstituted piperidines. A classical ammonium salt resolution was investigated to furnish chiral ( S )-1-benzyl-4-bromo-3-methyl-1,2,3,6-tetrahydropyridine as a valuable chiral precursor to C-3,4 di-substituted piperidines, which may have broader utility for other pharmaceutical intermediates. Specifically, in this work, in support of scale-up efforts for toxicology studies, we describe a practical synthesis to access kilogram quantities of enantiopure ( S )-1-benzyl-4-bromo-3-methyl-1,2,3,6-tetrahydropyridine, utilizing a Shapiro reaction, followed by a classical salt resolution with an inexpensive chiral acid in high yield and enantioselectivity.",10.1021/acs.oprd.1c00212,2021-10-01,0.5934722594777154
Organic Letters,A General Catalyst Controlled Route to Prostaglandin F2<sub>α</sub>,"High Resolution Image Download MS PowerPoint Slide We report a general, catalyst-controlled route to prostaglandin F2 α and its analogues. The approach uses a Rh-catalyzed dynamic kinetic asymmetric Suzuki–Miyaura coupling reaction between a racemic bicyclic allyl chloride and alkenyl boronic esters bearing chiral alcohols to give cyclopentyl intermediates bearing 3 contiguous stereocenters. The route provides advanced intermediates in 99% ee as a single diastereoisomer in all cases examined, with the absolute stereochemistry of the cyclopentane core controlled by the ligand. Intermediates that could be used to produce prostaglandin analogues such as bimatoprost, latanoprost, fluprostenol, and cloprostenol were synthesized. The final two stereocenters were installed via Pd-catalyzed Tsuji–Trost alkylation and iodolactonization. The synthesis of PG F2 α was achieved in 19% yield in 16 longest linear steps.",10.1021/acs.orglett.2c03718,2022-11-29,0.5934693905412706
Journal of the American Chemical Society,Dyotropic Rearrangement Facilitated Proximal Functionalization and Oxidative Removal of Angular Methyl Groups:  Efficient Syntheses of 23‘-Deoxy Cephalostatin 1 Analogues,"Oxidative functionalization (or removal) of a steroidal C18 methyl group is possible using a previously unknown dyotropic rearrangement of a seven-membered fused C-ring lactone to a 6-ring spiro lactone. Spiroketal equilibration led to the 23-deoxy South analogue of cephalostatin 1 (1) in only 12 steps (23% overall yield) from hecogenin acetate 4, and to strained diene South 1 analogue 30 in 11 steps (28% overall). Total synthesis of 23'-deoxy cephalostatin 1 (3) was accomplished in 16 operations from 4 (9% overall; average 86% yield per operation), and that of 16',17'-dehydro-23'-deoxy cephalostatin 1 (36) in 15 operations from 4 (8% overall; av 84%/op).",10.1021/ja017323v,2002-04-05,0.5934618151307047
Tetrahedron,A new synthesis of 2-fluoro-1-olefins,,10.1016/s0040-4039(00)94406-x,1990-01-01,0.5934588653192507
Journal of Organic Chemistry,"An Olefination Entry for the Synthesis of Enantiopure α,ω-Diaminodicarboxylates and Azabicyclo[<i>X</i>.<i>Y</i>.0]alkane Amino Acids","A new approach for synthesizing alpha,omega-diaminodicarboxylates of various chain lengths has opened the way for making a series of azabicyclo[X.Y.0]alkane amino acids of different ring sizes. beta-Keto phosphonates 21-23 were synthesized in 71-90% yield by the addition of the lithium anion of dimethyl methyl phosphonate to the omega-methyl ester of alpha-tert-butyl N-(PhF)aspartate 3, glutamate 9, and aminoadipate 12 (PhF = 9-phenylfluoren-9-yl). alpha,omega-Diaminodicarboxylates 24-26 of nine to eleven carbon chain lengths were prepared in 78-87% yield from the Horner-Wadsworth-Emmons olefination of alpha-tert-butyl N-(PhF)aspartate beta-aldehyde (5) with aminodicarboxylate-derived beta-keto phosphonates 21-23. The power of this approach for making azabicyclo[X.Y.0]alkane amino acid was then illustrated by the first synthesis of enantiopure indolizidin-9-one amino acid 2 in nine steps and >25% overall yield from inexpensive aspartic acid as chiral educt. Hydrogenation of (2S,8S)-di-tert-butyl 4-oxo-2,8-bis[N-(PhF)amino]non-4-enedioate (24) in 9:1 EtOH:AcOH furnished a 9:1 diastereomeric mixture of 6-alkylpipecolate 28 that was subsequently transformed into azabicyclo[4.3.0]alkane amino acid 2 via lactam cyclization and protecting group manipulations. Because alpha,omega-diaminodicarboxylates 25 and 26 may be similarly converted to heterocycles of larger ring sizes and because alkylation of similar ketones can be used to attach side-chains at different points on the heterocycle, this olefination strategy greatly expands our methodology for synthesizing azabicyclo[X.Y.0]alkane amino acids for the exploration of conformation-activity relationships of various biologically active peptides.",10.1021/jo9814602,1998-09-24,0.5934455548645592
Tetrahedron,Efficient one-pot synthesis of N-substituted phthalimides/naphthalimides from azides and anhydrides by iodotrimethylsilane,,10.1016/s0040-4039(98)01937-6,1998-11-01,0.5934440440148983
Tetrahedron,An efficient one-pot synthesis of substituted 2-aminobenzo-1-thiophene-3-carbonitriles,,10.1016/j.tetlet.2015.04.048,2015-04-21,0.5934440440148983
Organic Letters,"A Concise Asymmetric Synthesis of <i>cis</i>-2,6-Disubstituted <i>N</i>-Aryl Piperazines via Pd-Catalyzed Carboamination Reactions","A concise, modular, asymmetric synthesis of cis-2,6-disubstituted piperazines from readily available amino acid precursors is described. The key step in the synthesis is a Pd-catalyzed carboamination of a N1-aryl-N2-allyl-1,2-diamine with an aryl bromide. The products are obtained in 14-20:1 dr, with >97% ee, and the key cyclizations are the first examples of six-membered ring formation via Pd-catalyzed carboamination reactions of unsaturated amines with aryl halides.",10.1021/ol071241f,2007-07-25,0.5934414954281162
Synthesis,Practical Aspects in the Gram-Scale Synthesis of Chiral Diamino-Bithiophene ‘DAT2’ Ligand,"A gram-scale synthesis of the enantiomerically pure ligand DAT2 is described. The mild reaction conditions, operational simplicity, and satisfying isolated yield (68%) are some of the main features of this two-step reductive amination.",10.1055/s-2007-965953,2007-02-28,0.5934375157340309
Journal of the American Chemical Society,"Asymmetric Total Synthesis of 11-Deoxytetrodotoxin, a Naturally Occurring Congener","Tetrodotoxin, a toxic principle of puffer fish poisoning, is a specific blocker of sodium channel. Despite many synthetic efforts since the structure elucidation in 1964, the only total synthesis of the racemic tetrodotoxin has been reported by Kishi and co-workers. In the course of our studies directed toward the total synthesis to analyze biologically interesting issues associated with tetrodotoxin, we accomplished a highly stereocontrolled synthesis of (-)-5,11-dideoxytetrodotoxin in 1999. Based on the synthesis, we describe herein the first total synthesis of 11-deoxytetrodotoxin, a naturally occurring analogue. The synthesis started from an allylic alcohol, the same intermediate for the synthesis of 5,11-dideoxytetrodotoxin. Epoxidation of the allylic alcohol was followed by isomerization with Ti(i-PrO)(4) to give an alpha-hydroxy allylic alcohol, in which the configurations of the two hydroxyl groups were inverted by oxidation and then a 2-step reduction. Further epoxidation of the allylic alcohol and ozonolysis of the remaining vinyl group gave an aldehyde, which reacted with magnesium acetylide to give a propargyl alcohol in a stereoselective manner. Oxidative cleavage of the acetylenic moiety with RuO(4) afforded a fully functionalized lactone for 11-deoxytetrodotoxin. Crucial guanidinylation was achieved from trichloroacetamide according to our own method to give acetyldibenzylguanidine. Finally, deprotection of benzyl groups, acetates, and acetal furnished 11-deoxytetrodotoxin.",10.1021/ja0265153,2002-06-07,0.5934366399068929
Tetrahedron,A short step synthesis of ferrulactone I,,10.1016/s0040-4039(00)88482-8,1988-01-01,0.5934323845358724
Tetrahedron,A novel synthesis of (±)-trans-chrysanthemic acid,,10.1016/s0040-4039(00)77440-5,1980-01-01,0.5934302808530186
Synthesis,Novel Concise Synthesis of (±)-Noviose and l-(+)-Noviose by Palladium-Catalyzed Epoxide Opening,"We established a novel, concise synthetic route for obtaining noviose, the deoxy sugar component of aminocoumarin antibiotics. l-(+)-Noviose was successfully synthesized by utilizing a palladium-catalyzed epoxide-opening reaction and the subsequent lactone formation as key reactions, starting from a nonsugar chiral epoxide, which is easily available in both enantiomeric forms.",10.1055/s-0030-1258475,2011-03-14,0.5934269926062516
Tetrahedron,"Synthesis and conformational studies of 3,4-di-O-acylated furanoid sugar amino acid-containing analogs of the receptor binding inhibitor of vasoactive intestinal peptide",,10.1016/j.tetlet.2007.07.158,2007-07-31,0.5934253208760563
Angewandte Chemie International Edition,Concise Synthesis of Chiral Tricyclic Lactams by Tandem Dynamic Kinetic Asymmetric Reductive Amination/Lactamization Using Ammonium Salts,"The atom- and step-efficient synthesis of chiral fused tricyclic lactams from readily available ketoesters using cheap ammonium salts as the nitrogen source is reported. This ruthenium-catalyzed system operates through an efficient tandem dynamic kinetic asymmetric reductive amination (ARA)/lactamization and produces chiral fused tricyclic lactams in high yields with excellent diastereo- and enantioselectivity (up to >99 % ee, >20 : 1 dr and 98 % yield). The robust method was also applied to the concise synthesis of key intermediates in the synthesis of rivastigmine analogues and chiral N-heterocyclic carbene catalysts.",10.1002/anie.202303868,2023-04-22,0.5934251233264758
Organic Letters,Stereochemically Versatile Synthesis of the C1–C12 Fragment of Tedanolide C,"A flexible synthesis of the C1-C12 fragment of Tedanolide C has been accomplished in eight steps from 2-methyl-2,4-pentadienal. Asymmetric hydroformylation of a 1,3-diene allows for the late-stage generation of either C10 epimer with complete catalyst control. Diastereoselective addition of an isobutyryl β-ketoester dianion to an α,β-disubstituted chiral aldehyde sets the C5 stereochemistry while installing the geminal dimethyl unit. Differential protection of a syn-1,3-diol is performed as a highly efficient single-pot operation.",10.1021/ol300194x,2012-02-29,0.5934244072682416
Synlett,A Facile Total Synthesis ofAll Stereoisomers of Tarchonanthuslactone and Euscapholide fromChiral Epichlorohydrin,A versatile and facile synthetic route to all the stereoisomers of tarchonanthuslactone and euscapholide was developed using epichlorohydrin as the source of all the chiral centers.,10.1055/s-0028-1087524,2009-01-15,0.593413089394376
European Journal of Organic Chemistry,"Na<sub>2</sub>S<sub>2</sub>O<sub>8</sub>‐Promoted Radical Cyclization for the Synthesis of Azaspiro[4.5]deca‐3,6,9‐triene‐2,8‐dione and Pyrrolo[2,1‐<i>j</i>]quinolone Derivatives","An efficient radical cyclization of N ‐(4‐methoxyphenyl)‐ N ‐methyl‐3‐phenylpropiolamides with 1‐phenylcyclopropan‐1‐ols has been developed using Na 2 S 2 O 8 to produce azaspiro[4.5]deca‐3,6,9‐triene‐2,8‐diones in good yields with high selectivity. Similarly, the reaction of 1‐[6‐methoxy‐3,4‐dihydroquinolin‐1(2 H )‐yl]‐3‐phenylprop‐2‐yn‐1‐ones with 1‐phenylcyclopropan‐1‐ols provides 6,7‐dihydro‐3 H ‐pyrrolo[2,1‐ j ]quinoline‐3,9(5 H )‐dione derivatives. This is the first report on the use of cyclopropanols for the radical cyclization of N ‐(4‐methoxyphenyl)‐ N ‐methyl‐3‐phenylpropiolamides and 1‐[6‐methoxy‐3,4‐dihydroquinolin‐1(2 H )‐yl]‐3‐phenylprop‐2‐yn‐1‐ones.",10.1002/ejoc.201700058,2017-02-27,0.5934125703035643
Organic Letters,Synthesis of Aza Bicyclic Enones via Anionic Cyclization:  Application to the Total Synthesis of (−)-Brunsvigine,[reaction: see text] A general approach to the synthesis of aza bicyclic enones was developed via a simple two-step annulation involving a Mitsunobu protocol and anionic cyclization. According to this strategy the total synthesis of (-)-brunsvigine was accomplished with 12% overall yield.,10.1021/ol016022n,2001-06-20,0.5934098774123622
Angewandte Chemie International Edition,Remarkable Enhancement of Enantioselectivity in the Asymmetric Conjugate Addition of Dimethylzinc to (<i>Z</i>)‐Nitroalkenes with a Catalytic [(MeCN)<sub>4</sub>Cu]PF<sub>6</sub>–Hoveyda Ligand Complex,"An enantioselective copper-catalyzed asymmetric conjugate addition of Me2Zn to (Z)-nitroalkenes led to the formation of all-carbon quaternary stereogenic centers with high stereoselectivity. The key features of the new method are the unprecedented use of [(MeCN)4Cu]PF6 in conjunction with the Hoveyda ligand L1 and the use of (Z)-nitroalkene substrates so that undesired nitroalkene isomerization is minimized and enantioselectivity is enhanced dramatically. We also describe a novel, practical, and highly (Z)-selective nitroalkene synthesis.",10.1002/anie.201406247,2014-09-15,0.5934081635702606
Journal of Organic Chemistry,Stereocontrolled and Adaptable Synthesis of (−)-Aspergilone A via the Key Intermediate (+)-Phenol A,"High Resolution Image Download MS PowerPoint Slide We report the first total synthesis of (−)-aspergilone A, a citrinin-type azaphilone, and the determination of the absolute configuration of naturally occurring (+)-aspergilone A. The synthesis is centered around phenol A, a substructure of citrinin-type azaphilones, as the key intermediate. (+)-Phenol A was constructed using two sequential 1,2-boronate rearrangements with exceptional stereocontrol. Formally, this approach allows for the construction of all stereoisomers of phenol A without the need to change the synthetic procedure. The synthesis was completed in 11 steps with a total yield of 15.7% and >99% ee. The absolute configuration of (+)-aspergilone A was determined to be 3 R, 4 S .",10.1021/acs.joc.5c01650,2025-09-11,0.5934077664802093
Synthesis,Synthesis and Functionalization of Novel Tetrathia[7]helicenes as New Push-Pull Systems,"The synthesis of new functionalized 1,2-bis(benzodithienyl)ethenes as well as the preparation of the new tetrathia[7]helicenes are described. The helicenes reported are new chiral push-pull molecules, with potential application in optoelectronics.",10.1055/s-2006-950222,2006-10-26,0.5934034317419911
Organic Letters,Total Synthesis of Reveromycin A,"The stereoselective total synthesis of reveromycin A (1), a potent inhibitor of eukaryotic cell growth, has been accomplished on the basis of the stereocontrolled construction of the 6,6-spiroketal system, efficient succinylation of the tert-alcohol under high pressure, and the introduction of the unsaturated side chains.",10.1021/ol0060634,2000-06-23,0.5933977370250172
Journal of Organic Chemistry,A Molecular Cage Accessed by Threefold Click Reaction of a <i>C</i><sub>3<i>v</i></sub>-Symmetric Triazido-Functionalized Tribenzotriquinacene,"The hitherto unknown hexakis(halomethyl)-functionalized tribenzotriquinacenes (TBTQs) 9 and 10 were synthesized from the key 4b,8b,12b-tribromo-TBTQ derivative 6 by an improved route in 67% overall yield. Extension of the bowl-shaped framework of 9 or 10 by threefold condensation with propargylamine or 2-azidoethylamine afforded the corresponding TBTQ-trialkyne 11 and TBTQ-triazide 12, respectively. While attempts to construct bis-TBTQ cages, including homodimerization of 11 and heterocoupling of 11 with 12, were unsuccessful, triazide 12 was found to undergo threefold [3 + 2]-cycloaddition with 3-ethynylaniline and phloroglucinol tripropargyl ether under click chemistry conditions. The latter reaction enabled facile capping of the TBTQ bowl to give the novel cage compound 5 in 22% yield.",10.1021/acs.joc.3c01349,2024-01-25,0.5933862694242892
Organic Letters,Total Synthesis of Mycoplanecin A,"High Resolution Image Download MS PowerPoint Slide The first total synthesis of mycoplanecin A, a potent antitubercular macrocyclic depsipeptide natural product targeting the DnaN sliding clamp, is described. Interesting key steps are the synthesis of the two trans -4-alkylated- l -prolines via an iterative Matteson homologation and an O→N acyl shift observed during the fragment coupling of the building blocks. The challenging macrocyclization of the globally deprotected linear precursor was accomplished under optimized high-temperature, high-dilution conditions. This work provides chemical access to mycoplanecin A, enabling further biological investigation and analogue development against the important pathogen Mycobacterium tuberculosis .",10.1021/acs.orglett.5c02803,2025-08-01,0.5933860054719613
Journal of Organic Chemistry,"Synthesis of 1-Hydroxy-Substituted Pyrazolo[3,4-<i>c</i>]- and Pyrazolo[4,3-<i>c</i>]quinolines and -isoquinolines from 4- and 5-Aryl-Substituted 1-Benzyloxypyrazoles","1-Hydroxypyrazolo[3,4-c]quinoline (22), 1-hydroxypyrazolo[4, 3-c]quinoline (21), 1-hydroxypyrazolo[3,4-c]isoquinoline (20), and 1-hydroxypyrazolo[4,3-c]isoquinoline (19) were prepared from 1-benzyloxypyrazole (6), establishing the pyridine B-ring in the terminal step. The pyridine ring of pyrazoloquinolines 14 and 18 was formed via cyclization of a formyl group at C-4 or C-5 and an amino group of a 2-aminophenyl substituent at C-5 or C-4 in 1-benzyloxypyrazole. The pyridine ring of pyrazoloisoquinolines 5 and 9 was created via cyclization of a formyl group in a 2-formylphenyl substituent at C-4 or C-5 with an iminophosphorane group installed at C-5 or C-4 of 1-benzyloxypyrazole by lithiation followed by reaction with tosyl azide and then with tributylphoshine utilizing the Staudinger/aza-Wittig protocol. The 2-aminophenyl and the 2-formylphenyl substituent were introduced at C-5 or C-4 by regioselective metalation followed by transmetalation to the pyrazolylzinc halide and subsequent palladium-catalyzed cross-coupling with 2-iodoaniline or 2-bromobenzaldehyde. The order of reactions and use of protecting groups in the individual sequences have been optimized. The 1-benzyloxy-substituted pyrazoloquinolines and isoquinolines thus obtained were debenzylated by strong acid to the corresponding 1-hydroxy-substituted pyrazoloquinolines and isoquinolines 19-22.",10.1021/jo000986v,2000-12-01,0.5933832856531611
Synlett,One-Pot Generation of C≡X Bonds from Methyl 2-Siloxycyclopropanecarboxylates: Simple Syntheses of Functionalized Nitriles and Alkynes,"Starting from methyl 2-siloxycyclopropanecarboxylates simple and efficient one-pot procedures are described that lead to β-cyanoesters and methoxycarbonyl-substituted terminal alkynes. The prepared functionalized alkynes were subjected to typical transformations such as [3+2] cycloaddition providing triazole derivatives, Sonogashira coupling, Au-catalyzed hydrophosphorylation or a copper-catalyzed coupling of methyl diazoacetate furnishing alkyne 14 and allene derivative 15 . The Pauson–Khand reaction of the enyne 4c afforded a diastereomeric mixture of methyl 5-oxohexahydropentalen-2-carboxylate 16 in moderate yield.",10.1055/s-0034-1378370,2014-07-17,0.593382552455401
Journal of Organic Chemistry,Stereoselective Total Synthesis of Cytospolide P,"A short and convergent stereoselective total synthesis of biologically potent cytospolide P has been accomplished from acrolein. The salient features of our synthetic strategy include modified Crimmins aldols, Yamaguchi esterification, and Grubbs ring-closing metathesis reaction.",10.1021/jo501184t,2014-07-09,0.5933792524959246
Tetrahedron,Asymmetric synthesis of novel spirocycles via a chiral phosphoric acid catalyzed desymmetrization,,10.1016/j.tetlet.2019.03.074,2019-04-01,0.5933660409550271
Synlett,Synthesis of a Chiral Receptor Molecule with Converging Amidinium and Hydroxy Groups,All articles of this category The axially chiral amidinium ion 1 was synthesized by Suzuki cross coupling and by base induced cyclization of an amino nitrile intermediate. Receptor 1 may interact with guest molecules by three converging H-bond donors. chiral axis - guanidine - hydrogen bond - molecular recognition - Suzuki reaction,10.1055/s-1999-3095,1999-12-31,0.5933655875688275
Angewandte Chemie International Edition,Total Synthesis of (±)-Gelsemine,"A complex molecular reorganization (1-->2), a sequential anionic aza-Cope rearrangement and Mannich cyclization, and an unprecedented intramolecular Heck reaction of the tetrasubstituted double bond of a vinylogous carbamate are key steps in a new total synthesis of (+/-)-gelsemine (3). MOM=methoxymethyl, DBU=1,8-diazabicyclo[5.4.0]undec-7-ene.",10.1002/(sici)1521-3773(19991004)38:19<2934::aid-anie2934>3.0.co;2-l,1999-10-04,0.5933652498525572
Angewandte Chemie International Edition,Copper‐Catalyzed Tandem CN Bond Formation: An Efficient Annulative Synthesis of Functionalized Cinnolines,"Cinn-tillating synthesis: The combination of a readily available copper catalyst, a simple hydrazide nucleophile, and established difunctionalized building blocks provides a new, flexible route to an under-developed class of aromatic heterocycles, cinnolines (see scheme).",10.1002/anie.201201529,2012-04-26,0.5933635845108988
Synthesis,"Synthesis of the Constrained L-Methionine Analog, (<i>Z</i>)-L-2-Amino-4-methylthio-3-butenoic Acid","All articles of this category The methionine analog, ( Z )-L-2-amino-4-methylthio-3-butenoic acid ( 1 ) has been synthesized. The key intermediate, ( Z )-(±)-methyl 2-acetamido-4-methylthio-3-butenoate ( 7 ) was converted to 1 by enantioselective ester hydrolysis using alcalase to give ( Z )-L-2-acetamido-4-methylthio-3-butenoic acid ( 8 ), followed by enzymatic removal of the N -acetyl group using hog kidney acylase.",10.1055/s-1992-26177,1992-01-01,0.5933634186520447
Organic Letters,Novel Synthesis of Castanospermine and 1-Epicastanospermine,"[reaction: see text] Polyhydroxylated indolizidines have potential for treatment of HIV, hepatitis C and HSV infection, multiple sclerosis, angiogenesis, cancer, and diabetes. A new synthetic approach to the title compounds from a 5-C-methoxypyranosyl azide has been developed. The route incorporates the aldol reaction and a novel catalytic reductive amination cascade to generate the indolizidine ring.",10.1021/ol0508577,2005-05-27,0.5933617471708471
European Journal of Organic Chemistry,A General Methodology for the Enantioselective Synthesis of 1‐Substituted Tetrahydroisoquinoline Alkaloids,"Abstract Starting from tricyclic lactam 2 , which is easily accessible by cyclocondensation of δ‐oxoester 1 with ( R )‐phenylglycinol, a three‐step synthetic route to enantiopure 1‐substituted tetrahydroisoquinolines, including 1‐alkyl‐, 1‐aryl‐, and 1‐benzyltetrahydroisoquinoline alkaloids, as well as the tricyclic alkaloid (–)‐crispine A, has been developed. The key step is a stereoselective α‐amidoalkylation reaction using the appropriate Grignard reagent.",10.1002/ejoc.201000473,2010-06-11,0.5933610976382949
Journal of Organic Chemistry,A Modular Access to (±)-Tubocurine and (±)-Curine - Formal Total Synthesis of Tubocurarine,"Two consecutive Cu-catalyzed Ullmann-type C-O couplings permitted the first successful entry toward the curare alkaloids (±)-tubocurine and (±)-curine. Starting from vanillin, the synthetic sequence comprises 15 linear steps and includes a total of 24 transformations. In addition, the total synthesis of tubocurine represents a formal total synthesis of the famous arrow poison alkaloid tubocurarine.",10.1021/acs.joc.6b02647,2016-12-20,0.593356241914949
Synthesis,Synthesis of Optically Active N-(4-Hydroxynon-2-enyl)pyrrolidines: Key Building Blocks in the Total Synthesis of Streptomyces coelicolor Butanolide 5 (SCB-5) and Virginiae Butanolide A (VB-A),"Abstract Starting from 5-methylhexanal and (S)-configured N-propargylprolinol ethers, coupling delivered N-(4-hydroxynon-2-ynyl)prolinol derivatives as mixtures of C4 diastereomers. Resolution of the epimers succeeded after introduction of an (R)-mandelic ester derivative and subsequent HPLC separation. Alternatively, suitable oxidation gave the corresponding alkynyl ketone. Midland reagent controlled diastereoselective reduction afforded a defined configured propargyl alcohol with high selectivity. LiAlH4 reduction and Mosher analyses of the allyl alcohols enabled structure elucidation. The suitably protected products are used as key intermediates in enantioselective Streptomyces γ-butyrolactone signaling molecule total syntheses.",10.1055/s-0037-1610770,2021-04-15,0.5933548777955581
European Journal of Organic Chemistry,Regioselective Synthesis of 2‐Arylindoles via Palladium‐Catalyzed Cyclization of Phenylglyoxal and 2‐Anilinoacetophenones with Anilines,"A versatile route has been developed for the synthesis of 2‐arylindoles using a Pd‐catalyzed tandem process. Under reductive conditions, different 2‐arylindoles were synthesized from phenylglyoxal and aniline. This synthetic methodology involves a tandem reaction of four steps with high regioselectivity. Alternatively, 2‐anilinoacetophenones intermediates also can be using to give access to the corresponding 2‐arylindoles.",10.1002/ejoc.201900394,2019-05-20,0.5933497349993332
Tetrahedron,Facile synthesis of glucose-type 1-N-iminosugars: New inhibitor of glycolipid biosynthesis,A new type of glucose-based 1-N-iminosugars was synthesized from mannose and found to be a potent inhibitor of β-glucosidase (Ki 4.3 μM) and glycolipid biosynthesis.,10.1016/0040-4039(95)00119-w,1995-03-01,0.5933422323589727
Tetrahedron,Synthesis of fluorescent phosphatidylinositols using a novel inositol H-phosphonate,,10.1016/s0040-4039(98)00418-3,1998-05-01,0.5933421980801844
Tetrahedron,Novel synthesis of N-unsubsdtituted imidazoles using N-trimethylsilylimines,,10.1016/s0040-4039(00)61628-3,1993-01-01,0.5933421980801844
Angewandte Chemie International Edition,Enantioselective Palladium‐Catalyzed Decarboxylative Allylation of Carbazolones: Total Synthesis of (−)‐Aspidospermidine and (+)‐Kopsihainanine A,Functionalized chiral carbazolones with α-quaternary carbon centers are formed through the ligand-controlled Pd-catalyzed enantioselective decarboxylative allylic alkylation of carbazolones (see scheme). This catalytic asymmetric reaction was employed as the key step in the total synthesis of aspidospermidine and (+)-kopsihainanine A.,10.1002/anie.201209878,2013-03-08,0.5933387855601864
Synthesis,DMPU: An Alternative to HMPT in Moth Sex Pheromone Synthesis,"All articles of this category 1,3-Dimethyl-2-oxo-hexahydropyrimidine (DMPU, or N , N ′-dimethylpropyleneurea) is found to be a good substitute for the carcinogenic hexamethylphosphoric triamide (HMPT) as cosolvent in the alkylation of lithium 1-alkynides, key intermediates in moth sex pheromone synthesis.",10.1055/s-1988-27534,1988-01-01,0.5933372250350338
Tetrahedron,A synthesis of the HIV-protease inhibitor nelfinavir from d-tartaric acid,,10.1016/s0040-4039(01)01338-7,2001-09-01,0.5933360945993221
European Journal of Organic Chemistry,First Enantioselective Total Synthesis of Both (+)- and (−)-Metachromin A,"The antineoplastic agent (−)-metachromin A (1) from Hippospongia metachromia has been synthesized in enantiomerically pure form in 13% overall yield. A general convergent synthetic strategy for different metachromins using a 2-alkyloxy-3-sulfonyl-1,3-oxazolidine as a chiral dithienium equivalent is presented.",10.1002/1099-0690(200102)2001:4<647::aid-ejoc647>3.0.co;2-6,2001-02-01,0.59333586755432
Synlett,"Diastereoselective Ring Opening of Achiral Bridged Biaryls Using Chiral<i>O</i>- and<i>N</i>-Nucleophiles: First Atropo-Enantioselective Synthesis of (-)-4,4′-Bis(orcinol)<sup>1</sup>","All articles of this category The atropisomer-selective cleavage of the bridged biaryl 1 (3,8,10-trimethoxy-1-methyldibenzo[ b , d ]pyran-6-one), which has no stereogenic element, is described. The directed ring opening of the lactone bridge is achieved with chiral O - or N -nucleophiles, i.e. by external asymmetric induction. The application of this novel process to the first atropoenantioselective synthesis of the constitutionally symmetrical, known (-)-4,4′-bis(orcinol) 5 (6,6′-dimethyl-2,2′,4,4′-biphenyltetrol) is described.",10.1055/s-1991-20805,1991-01-01,0.5933341756789904
Tetrahedron,Synthetic applications of a three-component Mannich reaction. Total synthesis of IL-6 inhibitor (+)-madindoline A and B,,10.1016/j.tetlet.2006.07.083,2006-08-09,0.5933319810044987
Tetrahedron,Highly efficient synthesis of phenanthroquinolizidine alkaloids via Parham-type cycliacylation,,10.1016/j.tetlet.2009.12.135,2010-01-08,0.5933308591457535
Tetrahedron,A convenient stereoselective route to novel tetrahydroxyindolizidines,,10.1016/s0040-4039(02)02084-1,2002-11-01,0.5933295137159142
Journal of Organic Chemistry,"Synthesis of Reported and Revised Structures of Amathamide D and Synthesis of Convolutamine F, H and Lutamide A, C","Total synthesis of the published structure of amathamide D is described. Methyl 2,3,4-tribromo-5-hydroxybenzoate was selected as starting compound because it is readily accessible via acid-mediated Grob fragmentation-aromatization reaction of 1,4,5,6-tetrabromo-7,7-dimethoxybicyclo[2.2.1]hept-5-en-2-one. The aforementioned ester was transformed into the reported structure of amathamide D through methylation of a hydroxyl group and conversion of the ester moiety to a β-aminoethyl side chain. The NMR data of the synthetic compound did not conform to the reported natural product structure possessing contiguously positioned β-aminoethyl side chain, a set of three adjacent bromines, and a methyl ether linkage on the phenyl ring. This prompted us to redefine the natural product structure by synthesizing a product whose spectral data exactly matched with the reported data of amathamide D. The convolutamine H, with completely substituted phenyl ring adorned with an extra methyl ether functional group, has also been synthesized by application of Grob fragmentation-aromatization strategy to 3-(benzyloxy)-1,4,5,6-tetrabromo-7,7-dimethoxybicyclo[2.2.1]hept-5-en-2-one. This approach furnished directly methyl 2,3,4-tribromo-5,6-dimethoxybenzoate, which was converted straightforwardly into convolutamine H. Further, synthesis of convolutamine F and lutamide A and C is also described.",10.1021/jo3000173,2012-02-01,0.5933240066632148
Organic Letters,Synthesis of the 5-7-6 Core of Guanacastepenes. Construction of C8 Quaternary Carbon via the Inversion of Stereochemistry,[formula: see text] An efficient and unique route to the 5-7-6 core of guanacatepene A (1) is described. The installation of the desired stereochemistry at the C8 position was achieved via the desymmetrization of the cyclohexadienone by reductive ring closure of the seven-membered ring. That the closure of the seven-membered ring produced only the desired isomer is hypothesized to be a result of the more stable trans relationship between the C8 and C11 methyl groups.,10.1021/ol026820t,2002-09-25,0.5933166474403819
Synlett,A Versatile A-ring Synthesis for Taxol,"All articles of this category Careful A-ring substructure analysis for taxol has been carried out and a practical synthesis to all emergent substructures, viable as A-ring building blocks, has been developed. The synthesis starts from 2-methyl-1,3-cyclohexanedione and enters via ketalized trimethylvinyltriflate and ketalized trimethylester to trimethylketoalcohol(s) with the hydroxyl group protected. taxanes - palladium - methoxycarbonylation",10.1055/s-1996-5714,1996-12-01,0.593314487198216
Synthesis,A Direct Synthesis of 3-(Pyrrolidin-3-yl)indoles for Use As Conformationally Restricted Analogs of Tryptamines,"All articles of this category An efficient, two step synthesis of 3-(pyrrolidin-3-yl)indoles 4 is described. Indoles react with maleimides in refluxing acetic acid affording 3-(indol-3-yl)succinimides 6 . Reaction times and yields depend on the substituents on the indole 5 . Direct reduction of the succinimides 6 with LAH affords the desired conformationally restricted tryptamine derivatives 4 . 3-(pyrrolidin-3-yl)indoles - tryptamines - 3-(indol-3-yl)succinimides",10.1055/s-1997-1214,1997-04-01,0.593311132080894
Organic Letters,Formal Synthesis of (−)-Apicularen A,[reaction: see text] A formal synthesis of (-)-apicularen A has been completed. The synthesis features a cyanohydrin acetonide coupling as a convergent approach to the C9-C18 segment and an intramolecular Diels-Alder addition sequence to create both the 10-membered macrocycle and the aromatic ring.,10.1021/ol0353417,2003-08-15,0.5933102776611656
Tetrahedron,A novel and efficient method for the preparation of asymmetric dithioacetals,,10.1016/s0040-4039(00)82440-5,1988-01-01,0.5933082431844926
Synlett,"Highly Efficient Single-Step Synthesis of N,N-Dialkyl-1-ferrocenylethylamines via Ti(O<sup>i</sup>Pr)<sub>4</sub>Assisted Novel Reductive Aminations of Acetylferrocene","All articles of this category A simple, high-yield and straightforward procedure for the synthesis of N,N-dialkyl-1-ferrocenylethylamines, immediate precursors to chiral ferrocenyl P,N-ligands has been developed via novel reductive amination reactions of acetylferrocene using titanium(IV) isopropoxide and sodium borohydride.",10.1055/s-1994-23074,1994-01-01,0.5933079578722288
Synlett,Tartaric Acid Derived Aziridines as Chiral Precursors of 3-Amino-3-deoxy and 2-Amino-2-deoxy Tetroses: An Efficient Approach Towards Mugineic Acid,"All articles of this category Protected forms of 3-amino-3-deoxy-D-erythrose 2 and of 2-amino-2-deoxy-L-erythrose 11 have been enantiospecifically prepared starting from the diethyl L-tartrate derived aziridine 1 through a Pummerer rearrangement. Compound 2 was shown to be a convenient chiral building block for the synthesis of the 4-[2-(2- benzyloxycarbonylazetidin-1-yl)-1-benzyloxyethyl]-3- tert -butoxycarbonyl -2, 2-dimethyl-1,3-oxazolidine 3 , a precursor for mugineic acid.",10.1055/s-1992-21403,1992-01-01,0.5933042663184749
Organic Process Research & Development,"Accelerated Development of a Scalable Synthesis of CY6463, a CNS-Penetrant sGC Stimulator for the Treatment of Neurodegenerative Diseases","High Resolution Image Download MS PowerPoint Slide Soluble guanylate cyclase (sGC) stimulators are small molecules that increase nitric oxide (NO) signaling by binding to sGC, leading to an increase in cyclic guanosine monophosphate production. Such compounds have previously been studied clinically for noncentral nervous system (CNS) disorders. CY6463 is the first CNS-penetrant sGC stimulator to enter clinical trials and has the potential to positively impact a range of neurodegenerative diseases. In this paper, we present the development of an efficient, robust, and scalable synthesis of this compound that allowed for rapid generation of larger quantities of material, thereby accelerating advancement into early clinical studies, while minimizing the use of resources. The synthesis features a palladium-catalyzed one-pot Negishi coupling/cyanation sequence and a novel triazole formation from a Boc-protected amidrazone. Optimization of the reactions, safety considerations, and control of impurities, as well as a mechanistic study of the triazole formation reaction, are discussed.",10.1021/acs.oprd.1c00204,2021-09-13,0.5932957270316803
Synthesis,A New Route to the Synthesis of Pyranoflavone and Pyranochalcone Natural Products and their Derivatives,"The total synthesis of biologically active pyranoflavone natural products 1 and 2 was carried out starting from 2H-pyran. The synthesis of pyranochalcone natural products, lonchocarpin (9) and 4-hydroxylonchocarpin (10), and their derivatives 30-32 is described. This synthetic route also provides biologically interesting materials such as β-tubaic acid (24), desmethyl isoencecalin (25), and isoencecalin (27).",10.1055/s-2006-926294,2006-01-01,0.5932946585643752
Synthesis,Ring-Closing Metathesis as a Key Step in the Synthesis of 2-Pyridones and Pyridine Triflates,All articles of this category (opens in new window),10.1055/s-2008-1067180,2008-07-17,0.5932821251593219
Tetrahedron,Enantioselective amination of silylketene acetals with (N-arylsulfonylimino)phenyliodinanes catalyzed by chiral dirhodium(II) carboxylates: asymmetric synthesis of phenylglycine derivatives,,10.1016/j.tetlet.2007.10.087,2007-11-08,0.593281657595711
Synlett,Weinreb Amide Based New Synthetic Equivalents for Convenient Access to Immunosuppressive Agent FTY720 and Analogues,"Three new synthetic equivalents containing Weinreb amide functionality for the central core of FTY720, an immunosuppressive agent, have been developed. These synthetic equivalents enabled incorporation of the polar head group of FTY720, through Julia, Wittig, and Horner-Wadsworth-Emmons reactions and also allowed for variation in the chain length of the lipophilic side chain in target, through the Weinreb amide functionality therein. The use of tris(hydroxymethyl)aminomethane, commercially available at low cost for the polar head group offers a distinct advantage. Convenient reactions and simple functional group interconversions in good to high yield highlight the strength of the new route developed for the synthesis of clinically important FTY720.",10.1055/s-2007-990961,2007-10-19,0.5932732118928984
Journal of the American Chemical Society,Concise Total Syntheses of the Bioactive Mesotricyclic Diterpenoids Jatrophatrione and Citlalitrione,"The highly functionalized [5.9.5] tricyclic framework resident in jatrophatrione (1) and citlalitrione (2) has been synthesized. The route begins with the tandem anionic oxy-Cope rearrangement/methylation/transannular ene cyclization of 21 and subsequent introduction of a conjugated enone double bond. Hydroxyl-directed 1,4-reduction of this functionality in 25 with LiAlH(4)/CuI/hexamethylphosphoramide/tetrahydrofuran sets the stage for the implementation of a Grob fragmentation and expedited generation of 27. Stereocontrolled intramolecular hydrosilylation allows for the subsequent introduction of a cyclic carbonate as in 53. This intermediate undergoes remarkably efficient, fully regiocontrolled Treibs reaction to generate 54, with this maneuver serving as a pivotal step for making 1 available five steps later. Treatment of 1 with m-chloroperbenzoic acid leads to 2, with attack occurring preferentially on a alpha-face of the double bond more remote to the carbonyl.",10.1021/ja021177r,2003-01-11,0.5932680550352792
Journal of the American Chemical Society,Total Synthesis and Stereochemistry Revision of Mannopeptimycin Aglycone,"Development of efficient methods for preparation of bioactive nonribosomal peptides, containing densely functionalized nonproteinogenic amino acids, is an important task in organic synthesis. We have employed a concise synthesis for such amino acids by asymmetric aldol addition coupled with an isomeric resolution via diastereoselective cyclization. This approach is successfully applied to the first total synthesis of the cyclic hexapeptide aglycone of the mannopeptimycins, a group of glycopeptides known for potent activity against drug-resistant bacteria. The facile preparation of the key amino acids and the synthesis of the aglycone pave the way for further studies on this class of antibiotics and the development of new lead compounds with therapeutic potential. In addition, our studies have led to the revision of the stereochemistry of the β-methylphenylalanine residue in the mannopeptimycin aglycone.",10.1021/ja505105t,2014-07-31,0.5932665204618561
Journal of the American Chemical Society,Total Synthesis of Merrilactone A,"Merrilactone A (1) has been shown to possess neurotrophic activity and thus is expected to hold therapeutic potential in the treatment of neurodegeneration diseases. In this paper, we report the total synthesis of (+/-)-1, employing, as key steps, a novel desymmetrization protocol of meso-diketone to construct the core cis-bicyclo[3.3.0]octyl system of 1 (3 --> 2) and a radical cyclization to install the highly congested C9-quaternary carbon (16 --> 17).",10.1021/ja036587+,2003-08-13,0.5932664977822896
Organic Letters,Convergent Route to the Spirohexenolide Macrocycle,"Using key functional dissections, the synthesis of spirohexenolides is examined through a three-component strategy that features a 1,2-addition to couple tetronate and aldehyde components forming the C2-C3 bond and a Stille coupling to install the third sulfone-containing component. The macrocycle is completed by an intramolecular Julia-Kocienski reaction to form the C10-C11 trans-disubstituted olefin. Application of this strategy is described in progress toward the synthesis of (±)-spirohexenolide B.",10.1021/ol1018163,2010-09-17,0.5932634836439055
Journal of Organic Chemistry,Stereoselective Synthesis of the Diazonamide A Macrocyclic Core,Stereoselective synthesis of the right-hand heteroaromatic macrocycle of diazonamide A features C16-C18 bond formation in the Suzuki-Miyaura cross-coupling and atropodiastereoselective Dieckmann-type macrocyclization as key steps. The Suzuki-Miyaura cross-coupling gave the best yields when it was catalyzed by a palladium-dioxygen complex.,10.1021/jo5029419,2015-02-23,0.5932564888237959
European Journal of Organic Chemistry,"Total Synthesis of (±)‐8‐Oxo‐erythrinine, (±)‐8‐Oxo‐erythraline, and (±)‐Clivonine","Abstract Total syntheses of the erythrina alkaloids (±)‐8‐oxo‐erythrinine and (±)‐8‐oxo‐erythraline have been developed, based on a substrate‐controlled intramolecular 6‐ exo ‐ trig selective radical spirocyclization that establishes the quaternary center of the B‐rings. An improved total synthesis of (±)‐clivonine has also been reported, based on an intramolecular 6‐ endo‐trig free‐radical cyclization of a highly functionalized enamide, and a biomimetic ring‐switch of a lycorine‐type intermediate. These endo / exo ‐selective sequences enabled us to rapidly assemble two different complex alkaloids from a common building block in an economical fashion.",10.1002/ejoc.201500265,2015-04-07,0.5932520494875375
Tetrahedron,"An asymmetric synthesis of a 1α,25-dihydroxyvitamin D3 A-ring synthon",,10.1016/0040-4039(92)88109-i,1992-04-01,0.5932499270646149
Synthesis,"An Easy Access to 4,5-Disubstituted Thiazoles via Base-Induced Click Reaction of Active Methylene Isocyanides with Methyl Dithiocarboxylates","An efficient synthesis of 4,5-disubstituted thiazoles via base-induced cyclization of active methylene isocyanides such as tosylmethyl isocyanide, ethyl isocyanoacetate, and arylmethyl isocyanides with methyl arene- and hetarenecarbodithioates is reported. This synthesis could be a new click chemistry reaction, since it is simple, rapid, and often avoids purification steps. In addition, this method allow us a clear and general synthesis of novel 4,5-diarylthiazoles.",10.1055/s-0031-1290762,2012-04-05,0.5932495445945918
Tetrahedron,An efficient total synthesis of 9-methoxycarbazole-3-carbaldehyde based on a novel methodology for the preparation of methoxyindoles,,10.1016/s0040-4039(03)01745-3,2003-09-01,0.5932492748685632
Tetrahedron,Carbohydrates as chiral auxiliaries: synthesis of 2-hydroxy-β-D-glucopyranosides,,10.1016/0040-4039(91)80479-p,1991-12-01,0.5932489858687491
Journal of Organic Chemistry,Enantiospecific Synthesis of Annulated Nicotine Analogues from <scp>d</scp>-Glutamic Acid. 7-Azabicyclo[2.2.1]heptano[2.3-<i>c</i>]pyridines,"The conformationally restricted nicotinoid (1S,4S)-7-methyl-7-azabicyclo[2.2.1]heptano[2,3-c]pyridine dihydrochloride has been prepared enantiospecifically from D-glutamic acid. The method involved a lithium cis-2,6-dimethylpiperidide-mediated intramolecular anionic cyclization of (2S,5R)-N-(tert-butyloxycarbonyl)-5-[3-(4-N-chloropyridinyl]proline methyl ester in tandem with a standard decarboxylation sequence. Reductive amination afforded the desired N-methylated [2.2.1]bicyclonicotinoid. Cyclization of the corresponding iodopyridinylproline methyl ester, obtained via ultrasound-facilitated chloro-iodo exchange, was also effected.",10.1021/jo010534y,2001-09-26,0.5932468980167899
Tetrahedron,"Efficient syntheses of protected (2s,3s)-2,3-bis(hydroxymethyl)cyclobutanone, key intermediates for the synthesis of chiral carbocyclic analogues of oxetanocin",,10.1016/s0040-4039(00)97127-2,1990-01-01,0.5932438915965926
Organic Letters,"Total Synthesis of 7-Hydroxymurrayazolinine, Murrayamine D, and Mahanine via <i>m</i>-Nitro Group Activated Pyran Annulation","The facile total synthesis of the natural product (±)-mahanine was obtained in eight steps with an overall 52% yield from readily accessible known nitrophenol derivative 6. After a one-step, acid-catalyzed annulation, two additional natural products were formed including 7-hydroxymurrayazolinine, representing its first reported total synthesis. In the whole process, the introduction of the m-nitro group significantly enhanced the key pyran annulation reaction through inductive effects.",10.1021/acs.orglett.5b00422,2015-04-28,0.5932384885712096
Organic Letters,"Synthesis of Substituted Benzo[<i>b</i>]thiophenes via Sequential One-Pot, Copper-Catalyzed Intermolecular C–S Bond Formation and Palladium-Catalyzed Intramolecular Arene–Alkene Coupling of Bis(het)aryl/alkyl-1,3-monothiodiketones and <i>o</i>-Bromoiodoarenes","A new, convergent, one-pot synthesis of 2,3-substituted benzo[b]thiophenes from readily available 1,3-bis(het)aryl-1,3-monothiodiketones and o-bromoiodoarenes involving a sequential copper-catalyzed intermolecular C-S coupling followed by palladium-catalyzed intramolecular arene-alkene coupling of in situ generated β-(o-bromoaryl)thiovinylketones has been described. Synthesis of a few thieno- and furano-fused 2-(het)aroylethylidenethiochromenes via intramolcular direct C-H (het)arylation of β-(o-bromoaryl)thioenones carrying 2-thienyl/furyl groups under different palladium-catalyzed conditions has also been reported.",10.1021/acs.orglett.7b00273,2017-03-16,0.5932364115600172
Synthesis,"An Improved Synthesis of a Hydroxymethyl Tricyclic Ketone from Cyclohexanone, the Key Processes for the Synthesis of a Highly Potent Anti-inflammatory and Cytoprotective Agent","An improved synthesis of hydroxymethyl tricyclic ketone, (±)-(4a S ,8a S )-8a-(hydroxymethyl)-1,1,4a-trimethyl-3,4,4a,6,7,8,8a,9,10,10a-decahydrophenanthren-2(1 H )-one, in five steps (34% yield) from cyclohexanone has been successfully established. Accordingly, 10 grams of a highly potent anti-inflammatory and cytoprotective agent, (±)-(4b S ,8a R ,10a S )-10a-ethynyl-4b,8,8-trimethyl-3,7-dioxo-3,4b,7,8,8a,9,10,10a-octahydrophenanthrene-2,6-dicarbonitrile (TBE-31), was obtained in 15 steps (9.2% overall yield) via the hydroxymethyl tricyclic ketone from 32 grams of cyclohexanone.",10.1055/s-0033-1339900,2013-09-23,0.5932336710973772
Tetrahedron,"Concise synthesis of C2-symmetric trans-2,5-dioxymethylpyrrolidine derivatives by novel cyclization",,10.1016/s0040-4039(01)80661-4,1989-01-01,0.5932235987644353
Tetrahedron,Stereoselective synthesis of C-6 hydroxy tricyclic sulfone as a γ-secretase inhibitor,,10.1016/j.tetlet.2011.04.091,2011-05-03,0.5932200520553301
Tetrahedron,Formation of a novel thiopyranoindole ring system,,10.1016/s0040-4039(00)61266-2,1992-08-01,0.5932197301112169
Organic Letters,Merging Annulation with Ring Deconstruction: Synthesis of (<i>E</i>)-3-(2-Acyl-1<i>H</i>-benzo[<i>d</i>]imidazol-4-yl)acrylaldehyde Derivatives via I<sub>2</sub>/FeCl<sub>3</sub>-Promoted Dual C(sp<sup>3</sup>)–H Amination/C–N Bond Cleavage,"An unprecedented I 2 /FeCl 3 -promoted cascade reaction of aryl methyl ketones with 8-aminoquinolines for the convenient synthesis of ( E )-3-(2-acyl-1 H -benzo[ d ]imidazol-4-yl)acrylaldehydes was developed by merging annulation with ring deconstruction. This novel strategy unlocked the new reactivity of 8-aminoquinolines and provided an attractive platform for the ring opening of unactivated N -heteroaromatic compounds. Preliminary mechanistic investigation suggested that dual C(sp 3 )–H amination/C–N bond cleavage were key reaction steps. Furthermore, late-stage modification of the obtained products successfully delivered pyrazole and isoxazole derivatives, increasing the practicability and application potential of this methodology in organic synthesis.",10.1021/acs.orglett.1c00486,2021-03-19,0.5932162672246518
Angewandte Chemie International Edition,Unified Synthesis of Polycyclic Alkaloids by Complementary Carbonyl Activation**,"A complementary dual carbonyl activation strategy for the synthesis of polycyclic alkaloids has been developed. Successful applications include the synthesis of tetracyclic alkaloids harmalanine and harmalacinine, pentacyclic indoloquinolizidine alkaloid nortetoyobyrine, and octacyclic β-carboline alkaloid peganumine A. The latter synthesis features a protecting-group-free assembly and an asymmetric disulfonimide-catalyzed cyclization. Furthermore, formal syntheses of hirsutine, deplancheine, 10-desbromoarborescidine A, and oxindole alkaloids rhynchophylline and isorhynchophylline have been achieved. Finally, a concise synthesis of berberine alkaloid ilicifoline B was completed.",10.1002/anie.202102518,2021-03-26,0.593213867939036
Synlett,"Synthesis of 2-Alkylidenethiazolidine-4,5-diones and 2-Alkylideneoxazolidine-4,5-diones by One-Pot Cyclization of Arylacetonitriles with Heterocumulenes and Ethyl 2-Chloro-2-oxoacetate","2-Alkylidenethiazolidine-4,5-diones and 2-alkylidene­oxazolidine-4,5-diones have been prepared by one-pot cyclization of arylacetonitriles with heterocumulenes and ethyl 2-chloro-2-oxoacetate.",10.1055/s-2004-830863,2004-08-06,0.5932096796337507
Synthesis,"Three-Component Domino Heteroannulation and Synthesis of Some Novel Hexahydropyrimido[4,5-b]-1,8-naphthyridine Derivatives","An efficient protocol has been developed for the synthesis of some novel hexahydropyrimido[4,5- b ]-1,8-naphthyridine derivatives by a one-pot three-component reaction of a 2-cyano-3-(1 H -indol-3-yl)-pent-2-enedinitrile or ethyl-2,4-dicyano-3-(1 H -indol-3-yl)but-2-enoate derivative with an aryl aldehyde and a 6-aminouracil derivative. The indole derivatives were prepared by the reaction of the corresponding 3-(cyanoacetyl)indoles with acetonitrile derivatives.",10.1055/s-0034-1379639,2015-01-05,0.5932085933826572
Synlett,"A Novel Entry to 3,4,5-Trisubstituted 2-Pyrrolidones from Isoxazoline-N-oxides","A novel strategy for the synthesis of stereochemically defined 3,4,5-trisubstituted 2-pyrrolidones was developed. The suggested approach involves reductive domino-type recyclization of 3-aminomethyl-substituted isoxazolines as a key stage. The latter are prepared via α-C–H functionalization of readily available isoxazoline-N-oxides.",10.1055/s-0037-1610213,2018-07-31,0.593201997068638
Organic Letters,Total Synthesis of (−)-Przewalskin B,The first total synthesis of (-)-Przewalskin B has been accomplished with an intramolecular nucleophilic acyl substitution (INAS) reaction and an intramolecular aldol condensation as key steps.,10.1021/ol102593r,2010-12-09,0.59318733677945
Journal of Organic Chemistry,Total Synthesis of the Trisaccharide Antigen of the <i>Campylobacter jejuni</i> RM1221 Capsular Polysaccharide via de Novo Synthesis of the 6-Deoxy-<scp>d</scp>-<i>manno</i>-heptose Building Blocks,"A de novo approach utilizing the d -proline-catalyzed and LDA-promoted aldol reactions as key steps for the preparation of differentiated-protected 6-deoxy- d - manno -heptose building blocks was developed. PPh 3 AuBAr 4 F -catalyzed glycosylation with the 6-deoxy- d - manno -heptosyl o -hexynylbenzoate as donor was demonstrated as a direct and practical method for the stereoselective synthesis of the β-linked 6-deoxy- d - manno -heptoside as the major product. Coupling of the 6-deoxy-α- d - manno -heptosyl H-phosphonate with the 3-hydroxyl disaccharide acceptor based on H-phosphonate chemistry was described for the construction of the trisaccharide skeleton with the acid-labile phosphodiester linkage. Finally, first total synthesis of the unique trisaccharide antigen of the capsular polysaccharide of Campylobacter jejuni RM1221 that belongs to HS:53 serotype complex was accomplished for further evaluation as vaccine candidate against C. jejuni RM1221 infection.",10.1021/acs.joc.8b02394,2019-01-29,0.5931754341205221
Synthesis,Total Synthesis of the Didemnins; IV.<sup>1</sup>Synthesis of the Peptolide Ring and Construction of the Side Chain,"All articles of this category A total synthesis of didemnins A, B, and C ( 1-3 ) which enables these highly cytotoxic cyclopeptides to be prepared in decigram amounts is described. The ß-keto acid unit (hydroxyisovaleryl)propionic acid derivative (Hip, 6 ) was prepared by acylation of dibenzyl methylmalonate and subsequent cleavage of the benzyl groups by the action of boron trichloride. The free ß-keto acid 6 was activated by the DCC method and allowed to react with the leucine ester 7 to furnish the amide 8 . Activation, deprotection, and ring closure of the linear peptide 19 by means of the pentafluorophenyl ester method in a two-phase system gave rise to the didemnin ring skeleton in 75% yield within a few minutes. The respective side chains were then attached to the didemnin ring easily and in high yields by activation of Z-( R )- N -methylleucine as its 3-cyano-2-pyridylthiol ester followed by reaction with Z-lactylproline chloride and Z-lactic acid chloride.",10.1055/s-1991-26448,1991-01-01,0.5931710776650552
European Journal of Organic Chemistry,"Towards γ‐Rubromycin: Model Studies, Development of a C<sub>3</sub> Building Block, and Synthesis of 4′‐Silyl‐γ‐rubromycin","The human telomerase inhibitor γ‐rubromycin belongs to a class of natural products, which features a rare [5,6]‐bisbenzannulated spiroketal core as its central structural motif. Also termed “aromatic spiroketals”, these scaffolds pose great challenges to total synthesis. The ideal approach through an acid‐mediated spiroketalization event is demanding, since this transformation is susceptible to even slight electronic alterations on the polyaromatic ring system. Herein, we report our strategy towards this class of natural products, that led to the identification of an electronically well‐balanced spiroketalization precursor and eventually culminated in the preparation of an unnatural 4′‐silyl‐substituted γ‐rubromycin derivative in racemic form. In the course of this study, we additionally introduced a new type of γ‐silylated allylic phosphonate reagents that served as valuable C 3 building blocks to forge the spiroketalization precursor in a convergent manner.",10.1002/ejoc.201601224,2016-10-12,0.5931696604507695
Journal of Organic Chemistry,"Syntheses of 1-Amino-3-[2-(7-(2-hydroxyethyl)-1,7-dicarba-<i>closo</i>- dodecaboran(12)-1-yl)ethyl]cyclobutanecarboxylic Acid and Its <i>nido</i>-Analogue:  Potential BNCT Agents","The syntheses of unnatural amino acids, 1-amino-3-[2-(7-(2-hydroxyethyl)-1,7-dicarba- closo -dodecaboran(12)-1-yl)ethyl]cyclobutanecarboxylic acid ( 2 ) and its nido analog 1-amino-3-[2-(7-(2-hydroxyethyl)-1,7-dicarba- nido -dodecaboran(12)-1-yl)ethyl]cyclobutanecarboxylic acid ( 3 ) were achieved. The key steps in the syntheses of 2 and 3 involved the sequential dialkylation of m -carborane and an intramolecular ethoxide ion mediated cage degradation process.",10.1021/jo971060z,1997-12-01,0.5931615812278399
Angewandte Chemie International Edition,"Total Synthesis of (−)‐Cordycicadin D and 3,4‐ <i>trans</i> ‐Cordycicadins A and B: Entry to the 3,4‐ <i>trans</i> ‐Fused Cordycicadin Framework","polyketides, all containing a γ-lactone fused to a 10-membered lactone. The proposed biosynthetic pathway for the cordycicadins anticipates the formation of two more natural products which are unknown. We report the total synthesis of (-)-cordycicadin D and the two anticipated natural products 3,4-trans-cordycicadins A and B. The targets were convergently assembled, in a biomimetic fashion, via an efficient ketene trapping-intramolecular Michael addition sequence that delivered the requisite 3,4-trans-fused framework with high diastereoselectivity, enabled by the synthesis of complex dioxenones that serve as in situ ketene precursors. Recognition of the embedded polyketide symmetry enabled the use of a divergent-convergent synthetic strategy, based on the use of two products from an early-stage enzymatic resolution. The synthetic routes afforded (-)-cordycicadin D in 14 steps and 3,4-trans-cordycicadins A and B in 13 steps (longest linear sequence). This work confirms the structure of (-)-cordycicadin D and the observed instability of the anticipated natural product 3,4-trans-cordycicadin B during purification may explain why it is yet to be isolated.",10.1002/anie.202419989,2024-11-22,0.5931499391262576
Synthesis,A One Step Generation of α-Lithiotrimethylsilylalkanephosphonates. A New Preparative Route to Dialkyl 1-(Trimethylsilyl)alkanephosphonates and Vinylphosphonates,,10.1055/s-1986-31828,1986-01-01,0.5931488103277326
Journal of the American Chemical Society,Synthesis of (−)-Picrotoxinin by Late-Stage Strong Bond Activation,"We report a concise, stereocontrolled synthesis of the neurotoxic sesquiterpenoid (−)-picrotoxinin ( 1, PXN). The brevity of the route is due to regio- and stereoselective formation of the [4.3.0] bicyclic core by incorporation of a symmetrizing geminal dimethyl group at C5. Dimethylation then enables selective C–O bond formation in multiple intermediates. A series of strong bond (C–C and C–H) cleavages convert the C5 gem -dimethyl group to the C15 lactone of PXN.",10.1021/jacs.0c05042,2020-06-23,0.5931464392412314
Organic Letters,Total Synthesis and Elucidation of the Absolute Configuration of the Diterpene Tonantzitlolone,"[structure: see text] The first enantioselective total synthesis of tonantzitlolone, a novel 15-membered macrocyclic diterpene, utilized a Julia olefination, a highly selective, potassium enolate-based anti-Felkin aldol reaction, and an E-selective ring-closing metathesis as key C-C bond-forming steps. The absolute configuration of tonantzitlolone is established.",10.1021/ol047559e,2005-01-13,0.5931443433880969
Tetrahedron,Efficient two directional syntheses of a homophthalate ester and novel resorcylate oligomers,,10.1016/j.tetlet.2011.01.100,2011-02-02,0.593142808262961
Organic Letters,"General Route to Symmetric and Asymmetric<i>meso</i>-CF<sub>3</sub>-3(5)-Aryl(hetaryl)- and 3,5-Diaryl(dihetaryl)-BODIPY Dyes","A general efficient route to hitherto inaccessible symmetric and asymmetric meso-CF(3)-BODIPY dyes has been developed. The key stages include the reduction of available 2-trifluoroacetylpyrroles to the corresponding alcohols which are further condensed with pyrroles. The method allows the BODIPY with 3(5)aryl(hetaryl) and 3,5-diaryl(hetaryl) substituents to be readily assembled. The BODIPY dyes synthesized fluoresce (Φ(f) = 0.56-1.00) in the 560-680 nm region.",10.1021/ol200360f,2011-04-15,0.5931426888011312
Tetrahedron,"Synthesis of novel 2-(fluoroanilino)-3-(2,4-dinitroanilino) derivatives of 1,4-naphthoquinone",,10.1016/j.tetlet.2015.07.046,2015-07-18,0.5931345977858254
Tetrahedron,A novel and flexible synthesis of pyranose spiroacetal derivatives,,10.1016/s0040-4039(98)01247-7,1998-08-01,0.5931345977858254
Tetrahedron,A novel synthesis of the carbapen-2-em derivatives,,10.1016/s0040-4039(01)91335-8,1981-01-01,0.5931345977858254
Tetrahedron,Synthesis of novel dansyl-labeled Celecoxib derivatives,,10.1016/j.tetlet.2013.09.025,2013-09-19,0.5931345977858254
Tetrahedron,"Synthesis of novel 1,2-dihydropyrrolo[1,2-a]pyrazin-1(2H)-one derivatives",,10.1016/j.tetlet.2017.12.065,2017-12-23,0.5931345977858254
Tetrahedron,Novel synthesis of 3-halogenobenzo[b]tellurophene-derivatives,,10.1016/s0040-4039(01)86192-x,1979-01-01,0.5931345977858254
Tetrahedron,Synthesis of novel indenoquinolines and indenopyridazines via photoisomerization of benzotropolone derivatives,,10.1016/j.tetlet.2009.09.176,2009-10-09,0.5931345977858254
Tetrahedron,Synthesis of novel fluorinated 4-aminoquinoline derivatives,,10.1016/j.tetlet.2005.09.018,2005-09-22,0.5931345977858254
Chemical Science,"Synthesis, characterisation and biotransformation of novel 1, 4-dihydropyridine derivatives",,,2016-09-01,0.5931345977858254
Tetrahedron,A novel synthesis of p-phenylcalix[4]arenes tetraiodo derivatives,,10.1016/s0040-4039(00)97699-8,1990-01-01,0.5931345977858254
Tetrahedron,Synthesis of novel tricyclic isoindole derivatives,,10.1016/j.tetlet.2003.09.065,2003-10-15,0.5931345977858254
Tetrahedron,"Synthesis of novel fluorinated 4H-benzo[h]chromen-4-one and 4H-pyrano[3,2-h]quinolin-4-one derivatives",,10.1016/j.tetlet.2007.11.146,2007-12-05,0.5931345977858254
Tetrahedron,"Synthesis of peptidylglycophospholipids, novel derivatives of muramyl-dipeptide",,10.1016/s0040-4039(01)92921-1,1981-01-01,0.5931345977858254
Tetrahedron,A new regioselective synthesis of N1- and N8-monoacylated spermidines,,10.1016/s0040-4039(00)99466-8,1989-01-01,0.5931274934392298
Tetrahedron,Regioselective synthesis of new biheterocyclic triazepines,,10.1016/s0040-4039(97)00290-6,1997-03-01,0.5931274934392298
Organic Letters,"Total Synthesis of Nostodione A, a Cyanobacterial Metabolite","The first total synthesis of the mitotic spindle poison nostodione A is described. The inherent oxidative sensitivity of indoles is utilized for a late introduction of a second carbonyl to the cyclopent[b]indole-2-one system. The tricyclic system is prepared from indole-3-acetic acid and O-silylated 4-ethynylphenol, using a stereoselective intramolecular reductive Heck cyclization as the key transformation.",10.1021/ol303036j,2012-12-10,0.5931255705549248
Tetrahedron,"A novel synthesis of selenium heterocycles: substituted 1,2,3-selenadiazoles",,10.1016/s0040-4039(01)88895-x,1969-01-01,0.5931168777894171
Synthesis,A Novel Synthesis of (<i>E</i>)-Substituted Styryl (<i>Z</i>)-Styryl Sulfones,,10.1055/s-1984-30827,1984-01-01,0.5931168777894171
Tetrahedron,A novel synthesis oftrans-enynes from substituted tetrahydropyrans,,10.1016/s0040-4039(99)01176-4,1999-08-01,0.5931168777894171
Synthesis,A Novel Synthesis of 2-Substituted Indans,,10.1055/s-1977-24422,1977-01-01,0.5931168777894171
Tetrahedron,A novel synthesis of substituted naphthalenes,,10.1016/s0040-4039(96)02435-5,1997-02-01,0.5931168777894171
Tetrahedron,The synthesis and characterisation of novel o-substituted benzyldi-t-butylphosphine–boranes,,10.1016/j.tetlet.2008.12.006,2008-12-09,0.5931168777894171
Tetrahedron,A novel synthesis of substituted 3-aminopenems,,10.1016/s0040-4039(00)96102-1,1987-01-01,0.5931168777894171
Tetrahedron,"Synthesis of novel hydroperoxy-substituted 1,2,4,5-tetroxepanes and 1,2,4,5-tetroxocanes",,10.1016/s0040-4039(98)01375-6,1998-09-01,0.5931168777894171
Tetrahedron,Benzopyrones. Part XII. Novel synthesis of some 3-substituted chromones,,10.1016/s0040-4039(00)74607-7,1976-02-01,0.5931168777894171
Tetrahedron,Umpolung of tropone: The synthesis of novel 2-substituted tropones via 2-halocycloheptadienone enolates,,10.1016/s0040-4039(00)80591-2,1988-01-01,0.5931168777894171
Synthesis,A Novel Synthesis of Substituted 2-Oxopiperidines,,10.1055/s-1976-24142,1976-01-01,0.5931168777894171
Tetrahedron,A novel indole synthesis,,10.1016/s0040-4039(00)91741-6,1976-07-01,0.5931094106767807
Organic Letters,"Total Synthesis of (−)-5,6,11-Trideoxytetrodotoxin and Its 4-Epimer","[reaction: see text] The first total synthesis of 5,6,11-trideoxytetrodotoxin (1) and its 4-epimer were achieved. The synthesis is characterized by the stereoselective construction of the quaternary amino carbon center at C8a by an asymmetric transferring Strecker synthesis and the highly efficient conversion of cyanohydrin 4 to 1 via intramolecular cyclization reactions.",10.1021/ol062098d,2006-09-15,0.5931007189511048
Journal of Organic Chemistry,"Divergent Synthesis of α,γ-Disubstituted γ-Butyrolactones through Diastereoselective Bromolactonization with Alkali Metal Bromide: Asymmetric Total Synthesis of (+)-Dubiusamine C","A divergent synthesis of α-substituted bromomethyl γ-lactones was developed, which involves the diastereoselective bromolactonization of α-substituted 4-pentenoic acids and 4-pentenamides via umpolung of bromide by use of alkali metal bromide and Oxone (potassium peroxymonosulfate mixture, 2KHSO5·KHSO4·K2SO4) to obtain mainly cis-products from α-substituted 4-pentenoic acids and trans-products from α-substituted 4-pentenamides, and it was found that the bromonium species generated from KBr and Oxone had higher activity than N-bromosuccinimide. Furthermore, the asymmetric total synthesis of (+)-dubiusamine C, which was isolated as a minor diastereomer from Pandanus dubius, was accomplished for the first time through the cis-selective bromolactonization of (S)-α-methyl-4-pentenoic acid in nine linear steps and 36% overall yield.",10.1021/acs.joc.5b01497,2015-08-27,0.5931004056250869
Synlett,"Three-Component Coupling–Oxidative Amidation–Heterocycloannulation: Synthesis of the Indole Alkaloids Hamacanthin A and trans-2,5-Bis(3′-Indolyl)piperazine","Concise and highly convergent syntheses of antifungal marine bis(indole) alkaloids, hamacanthin A and trans -2,5-bis(3′-indolyl)piperazine is described. The total synthesis of hamacanthin A is ­accomplished via the oxidative amidation–chemoselective heterocycloannulation of 2,2-dibromo-1-(1 H -indol-3-yl)ethanone with 1-(1 H -indol-3-yl)ethane-1,2-diamine. The reduction of desbromo hamacanthin with aluminum borohydride afforded the alkaloid trans -2,5-bis(3′-indolyl)piperazine. Two novel and convenient protocols for the synthesis of indolyl-1,2-diaminoethane are also developed in moderate to good yields.",10.1055/s-0036-1588961,2017-03-08,0.5930993972526818
Tetrahedron,Oxidative fragmentation of 3-aryl-1-(tetrazol-5′-yl)triazenes: a new route to aryl diazocyanides.,,10.1016/s0040-4039(00)98308-4,1985-01-01,0.5930990203094025
Organic Letters,Total Synthesis of Elaiolide Using a Copper(I)-Promoted Stille Cyclodimerization Reaction,The 16-membered macrodiolide elaiolide (2) has been prepared in 20 steps from the ketone ( S )-8 in 9.3% overall yield with a diastereoselectivity of 76%. Key steps included the copper(I) thiophene-2-carboxylate promoted cyclodimerization of the vinyl stannane 3 to give the C 2 -symmetric macrocycle 16 in 80% yield and the two-directional aldol coupling of the macrocyclic diketone 17 with aldehyde 5. Most of the stereocenters in the macrocyclic precursor 3 were constructed using boron aldol methodology developed in this laboratory.,10.1021/ol990004c,1999-05-17,0.5930928163375543
Synlett,Synthesis of Tetrasubstituted Pyrazoles through Different Cyclization Strategies; Isosteres of Imidazole Fungicides,"Formerly unknown 3-chloro-4,5-diaryl-1-methylpyrazoles have been prepared through two different synthesis pathways, one of which starts from 2,3-diarylacrylonitriles, the second from 3,3-dichloro-1,2-diarylpropenones. Both approaches rely on the cyclocondensation of diarylated three-carbon synthons with hydrazine derivatives and possess some unique features. One route uses a cyclization reaction, during which a chlorine atom is directly installed at the pyrazole ring that normally would be introduced in subsequent halogenation steps. The second pathway applies the Sandmeyer reaction to introduce this chloro substituent; an approach that is rarely described at the pyrazole nucleus. The obtained tetrasubstituted pyrazoles are isosteres of highly active imidazole fungicides and show good control of Uncinula necator (grape powdery mildew).",10.1055/s-0033-1338433,2013-04-18,0.5930896268387719
Organic Process Research & Development,Utilization of Sequential Palladium-Catalyzed Cross-Coupling Reactions in the Stereospecific Synthesis of Trisubstituted Olefins,"A stereospecific synthesis of the drug-candidate 1 is described. The synthetic sequence, aimed at accomplishing modularity and cost savings, features a series of organometallic steps to afford stereospecifically the desired trisubstituded olefin active pharmaceutical ingredient. Key developments consist of a mild Sonogashira reaction of aryl bromide 7a with the polymerization prone propargyl alcohol and a stereospecific hydroalumination, Zn/Al exchange, and Pd-catalyzed cross-coupling sequence facilitated by the commercially available PEPPSI catalyst.",10.1021/op900015g,2009-04-22,0.593089117881446
European Journal of Organic Chemistry,Synthesis of Enantiomerically Pure Morphan Analogues from α-D-Glucose,"The synthesis of the enantiomerically pure morphan analogue 19 starting with the methyl glucopyranoside 6 is described. Homologation, reduction, and acylation provide the heptopyranosamine derivatives 9a−c. After removal of the hydroxy group of 9c the intramolecular N/O-acetal formation of the Cbz-protected heptopyranosamine 18 succeeds to yield the morphan analog epoxyazocane 19.",10.1002/1099-0690(200101)2001:1<115::aid-ejoc115>3.0.co;2-f,2001-01-01,0.5930695559864883
Organic Letters,Concise Total Synthesis of (±)-<i>cis</i>-Trikentrin A and (±)-Herbindole A via Intermolecular Indole Aryne Cycloaddition,"An efficient nine-step total synthesis of the annulated indole natural products (+/-)-cis-trikentrin A and (+/-)-herbindole A was accomplished via an intermolecular Diels-Alder cycloaddition using our recently developed indole aryne (indolyne) methodology as the key step. This strategy provides rapid access into the trikentrins and the related herbindoles and represents the first application of this methodology to natural products total synthesis. The required 6,7-indolyne precursor was readily constructed by means of the Bartoli indole synthesis with substituted nitrobenzenes and vinyl magnesium bromide.",10.1021/ol802425m,2008-12-04,0.5930679888309501
Synlett,"Diastereoselective Synthesis of the Acyl Side-Chain and Amino Acid (2<i>S</i>,3<i>R</i>)-3-Hydroxy-3-Methylproline Fragments of Polyoxypeptin A","Synthesis of the acyl side-chain and amino acid (2S,3R)-3-hydroxy-3- methylproline units of the potent depsipeptide polyoxypeptin A, is described. Key intermediates were secured via diastereoselective addition involving a homoenolate ion and allylation of an aminoketone, respectively.",10.1055/s-2005-918924,2005-01-01,0.593066803285841
Journal of the American Chemical Society,Total Synthesis and Absolute Stereochemical Assignment of Kibdelone C,"Kibdelones are hexacyclic tetrahydroxanthones and potent anticancer agents isolated from an Australian microbe. Herein, we describe the synthesis of a chiral, nonracemic iodocyclohexene carboxylate EF ring fragment of the kibdelones employing an intramolecular iodo halo-Michael aldol reaction and its merger with an ABCD ring fragment to afford the congener kibdelone C.",10.1021/ja203642n,2011-06-07,0.5930555275812858
Journal of Organic Chemistry,Studies toward the Enantioselective Syntheses of Oxylipins:  Total Synthesis and Structure Revision of Solandelactone E,"An efficient and general entry to unsaturated cyclopropane- and lactone-containing oxylipins of marine origin has been designed and applied to the first enantioselective total synthesis of solandelactone E. The synthesis, which proceeds in a total of 23 steps from commercially available materials, features a diastereoselective acetal-directed cyclopropanation of an electron-deficient diene, a regioselective Sharpless enantioselective dihydroxylation, and a stereoselective [2,3]-sigmatropic rearrangement of a selenoxide to effect a 1,3-transposition of an allylic alcohol. Comparison of spectral data for the synthetic solandelactone, thus prepared, with data in the literature led to a revision of the original structural assignments of the C(11)-epimeric solandelactones.",10.1021/jo701739v,2007-12-19,0.593053490217815
European Journal of Organic Chemistry,A Highly Convergent Synthesis of Myristoyl‐carba(dethia)‐coenzyme A,"Co-translational myristoylation of the N-terminal glycine residue of diverse signaling proteins is required for membrane attachment and proper function of these molecules. The transfer of myristate from myristoyl-coenzyme A (myr-CoA) is catalyzed by the enzyme N-myristoyltransferase (Nmt). Nmt has been implicated in a number of human diseases, including cancer and epilepsy, as well as pathogenic mechanisms such as fungal and virus infections, including HIV and Hepatitis B. Rational design has led to the development of potent competitive inhibitors, including several non-hydrolysable acyl-CoA substrate analogues. However, linear synthetic strategies, following the route of the original CoA synthesis, generate such analogues in very low over all yields that typically are not sufficient for in vivo studies. Here, we present a new, highly convergent synthesis of myristoyl-carba(dethia)-coenzyme A 1 that allows to obtain this substrate analogue in 11-fold increased yield compared to the reported linear synthesis. In addition, enzymatic cleavage of the adenosine-2',3'-cyclophosphate in the last step of the synthesis proved to be an efficient way to obtain the isomerically pure 3'-phosphate 1.",10.1002/ejoc.200901410,2010-02-16,0.5930433563303558
Synthesis,"Pheromone Synthesis, CCVIII: Synthesis of (1S,3S,7R)-3-Methyl-α-himachalene, the Sex Pheromone of the Sandfly Lutzomyia longipalpis from Jacobina, Brazil","All articles of this category (1 S ,3 S ,7 R )-3-Methyl-α-himachalene, the sex pheromone of the male sandfly ( Lutzomyia longipalpis ) from Jacobina, Brazil, was synthesized enantioselectively by employing Evan's or Oppolzer's asymmetric methylation and intramolecular Diels-Alder reaction as the two key steps. The absolute configuration of the product was unambiguously established by X-ray analysis of a compound related to one of the synthetic intermediates. The ring junction of this sandfly pheromone possesses the absolute configuration opposite to that of the known (1 R ,7 R )-α-himachalene of plant origin. asymmetric synthesis - Diels-Alder reactions - Lutzomyia longipalpis - pheromones - terpenoids",10.1055/s-2000-8220,2000-01-01,0.5930430786086209
Organic Letters,One-Pot Synthesis of 3-Difluoromethyl Benzoxazole-2-thiones,"A one-pot strategy for the diversified synthesis of 3-difluoromethyl benzoxazole-2-thiones is reported. The reaction of 2-aminophenol, sodium chlorodifluoroacetate, and elemental sulfur in the presence of NaO t-Bu gives exclusively 3-difluoromethyl benzoxazole-2-thiones in good yield (up to 98%). The mechanism of this reaction presumably involves first cyclization of 2-aminophenols with thiocarbonyl fluoride, followed by N-difluoromethylation with difluorocarbene. The developed synthetic procedures are versatile, robust, and easily scalable for the synthesis of 3-difluoromethyl benzoxazole-2-thione derivatives, some of which have shown insecticidal activities.",10.1021/acs.orglett.8b02713,2018-10-10,0.5930393556340184
Journal of Organic Chemistry,Palladium-Catalyzed Synthesis of Isocoumarins and Phthalides via <i>tert</i>-Butyl Isocyanide Insertion,"A novel and highly efficient strategy for the synthesis of isocoumarins and phthalides through a palladium(0)-catalyzed reaction incorporating tert-butyl isocyanide has been developed. This process, providing one of the simplest methods for the synthesis of this class of valuable lactones, involves two steps including cyclization reaction and simple acid hydrolysis. The methodology is tolerant of a wide range of substrates and applicable to library synthesis.",10.1021/jo302004u,2012-10-26,0.593039144670106
Organic Letters,An Efficient and Scalable Synthesis of Substituted Phenanthrenequinones by Intramolecular Friedel−Crafts Reaction of Imidazolides,"An efficient synthesis of 9,10-phenanthrenequinones is described. The two carbonyl groups were introduced by an orthoselective intermolecular Friedel-Crafts reaction of 3-methoxyphenol with ethyl chlorooxoacetate. The formation of a biaryl bond by Suzuki-Miyaura coupling reaction, followed by the hydrolysis of the ester, gave a biaryloxoacetic acid. Treatment of this acid with CDI gave the corresponding imidazolide. The ring closure to the desired phenanthrenequinone was accomplished by intramolecular Friedel-Crafts reaction of the imidazolide promoted by TiCl(4).",10.1021/ol071261h,2007-09-20,0.593031686052067
Synlett,New Access to Kainic Acid via Intramolecular Palladium-Catalyzed Allylic Alkylation,"The formal synthesis of kainic acid was carried out in eleven steps. The key cyclization step was accomplished through an intramolecular palladium-catalyzed allylic alkylation of an allylic sulfone. Further functionalization of the resulting pyrrolidone ­featured, inter alia, a N-heterocyclic carbene-copper hydride (NHC-CuH)-mediated stereoconvergent conjugate reduction.",10.1055/s-2007-982542,2007-06-01,0.5930184191716992
Synlett,An Enantiospecific Formal Total Synthesis of the 5-8-5 Tricyclic Diterpene ent-Fusicoauritone,"An enantiospecific formal total synthesis of the 5-8-5 tricyclic diterpene fusicoauritone has been accomplished, starting from 5-isopropyl-2-methylcyclopent-1-enemethanol [available in three steps from (R)-dihydrolimonene] employing two ring-closing-metathesis reactions for the construction of the eight- and five-membered rings.",10.1055/s-0031-1290095,2011-12-09,0.593015320167734
Tetrahedron,"An efficient synthesis of novel heterocycle-fused derivatives of 1-oxo-1,2,3,4-tetrahydropyrazine using Ugi condensation",,10.1016/j.tetlet.2004.11.168,2004-12-22,0.5929945441302602
European Journal of Organic Chemistry,Stereoselective Construction of Entire Diastereomeric Stereotetrads Based on an Asymmetric Morita–Baylis–Hillman Reaction,"A method for the enantio‐ and diastereoselective construction of all possible stereoisomers of a polypropionate stereotetrad having four contiguous stereogenic centers has been developed. The approach features an iterative sequence of cinchona‐alkaloid‐catalyzed Morita–Baylis–Hillman reaction and subsequent diastereoselective hydrogenation. By this method, benzaldehyde was successfully converted into eight diastereoisomeric 3,5‐dihydroxy‐2,4‐dimethyl‐5‐phenylpentanoic acid ester derivatives with high enantiomeric purities (99 % ee ) in 25–67 % overall yield (eight steps) in a reagent‐controlled manner.",10.1002/ejoc.201700337,2017-04-05,0.5929896658826406
Organic Process Research & Development,"Practical Synthesis of Reactive Immuno-PET Linker-Chelator (1<i>R</i>,2<i>R</i>)-RESCA-TFP","We herein report the evolution of decagram syntheses of a single enantiomer of immuno-PET linker-chelator (1 R,2 R )-RESCA-TFP ( 1 ) from commercially available (1 R,2 R )-1,2-diaminocyclohexane. The syntheses feature a reductive amination, a trialkylation, a saponification followed by EDCI-promoted TFP ester formation, and finally a t -Bu ester global deprotection. While the first-generation synthesis required chromatographic purification of process intermediates and 1, the second-generation synthesis implemented salt formation and direct isolation by filtration, thus eliminating all preparative purification operations.",10.1021/acs.oprd.3c00149,2023-06-28,0.5929862062386059
Synthesis,"Facile Strategy to Access the Indolo[2,3-a]quinolizidine Framework: Synthetic Study on Tangutorine","An asymmetric synthetic approach to indolo[2,3-a]quinolizidine framework has been developed involving Horner–Wadsworth–Emmons olefination and reductive amination as the key steps. Further, the developed strategy was explored towards the synthesis of tangutorine using Evans aldol reaction for the preparation of desired aldehyde.",10.1055/s-0039-1690004,2019-07-24,0.5929850491667
Synlett,An Efficient Synthesis of Substituted Hydrazides,"Routes for the selective synthesis of 1-, or 2-substituted hydrazides, and 1,2-disubstituted hydrazides are reported. These routes proceed via cyanoborohydride reduction of stable acyl ­hydrazone intermediates.",10.1055/s-2005-869858,2005-06-07,0.5929841842284136
Tetrahedron,Hashish: Synthesis of (−)-Δ9-tetrahydrocannabinol (THC) and its biologically potent metabolite 3′-hydroxy-Δ9-THC.,,10.1016/s0040-4039(01)93544-0,1979-01-01,0.5929800131174402
Organic Letters,Tandem Conjugate Cyanide Addition−Dieckmann Condensation in the Synthesis of the ABCD-Ring System of Lactonamycin,An efficient synthesis of the ABCD-ring system of lactonamycin (1) is reported in this Letter. The key step is the tandem cyanide conjugate addition-Dieckmann condensation of alkyne 17 to afford a fully functionalized anthracene. Selective reduction of the cyano group with subsequent lactam formation affords the tetracyclic core of lactonamycin 19. [reaction: see text],10.1021/ol0257373,2002-03-15,0.5929788303598313
Organic Process Research & Development,Development of the Late-Phase Manufacturing Process of ZPL389: Control of Process Impurities by Enhanced Process Knowledge,"The development of the late-phase manufacturing process of the drug candidate ZPL389 and the strategies for the control of impurities are outlined in detail. Selective salt formation at several stages was pivotal to controlling the process impurities. The extensive optimization of the N-methylation of a Boc-protected amine with dimethyl sulfate and of a nucleophilic aromatic substitution without the use of metal catalysts led to a robust, scalable process. The process was demonstrated on a >100 kg scale. Overall, improved drug substance quality, higher yield, and reduction of the process mass intensity were achieved.",10.1021/acs.oprd.1c00077,2021-04-14,0.5929743382272478
European Journal of Organic Chemistry,A General Synthesis of Disubstituted Rubicenes,"The synthesis of novel disubstituted rubicenes 1a–k is described. Starting from 1,5-dichloroanthraquinone and aryllithium reagents 3, the diol adducts 4 are reduced and the resulting diarylanthracenes 5 are cyclized to afford the title compounds in fair to good overall yield.",10.1002/(sici)1099-0690(199812)1998:12<2769::aid-ejoc2769>3.0.co;2-7,1998-12-01,0.592966906943088
Synlett,"Transition Metals in Organic Synthesis, Part 97:¹ Silver-Catalyzed Synthesis of Hexahalogenated 2,2′-Bipyrroles","We describe the synthesis of three hexahalogenated 1,1′-dimethyl-2,2′-bipyrroles using an efficient silver(I)-catalyzed cyclization as key step.",10.1055/s-0031-1289563,2011-10-31,0.5929665434825182
Organic Process Research & Development,"Practical and Large-Scale Synthesis of <i>r</i><i>ac</i>-(3<i>S</i>,4a<i>R</i>,10a<i>R</i>)- 6-Methoxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[<i>g</i>]quinoline-3-carboxylic Acid Methyl Ester","3- Substituted octahydrobenzo[ g ]quinolines are important intermediates for pharmaceutically active compounds. A short, efficient synthesis, which is feasible for large-scale manufacturing of rac -(3 S,4a R,10a R )-6-methoxy-1-propyl-1,2,3,4,4a,5,10,10a-octahydrobenzo[ g ]quinoline-3-carboxylic acid methyl ester is presented. As starting materials the cheap and readily available 1,6-dimethoxynaphthalene and ethoxymethylenecyanoacetic acid ethyl ester were chosen. All atoms of the skeleton were introduced in the first step, by the reaction of 7-lithiated 1,6-dimethoxynaphthalene with ethoxymethylenecyanoacetic acid ethyl ester. Subsequent hydrogenation, followed by Birch reduction and acidic cyclization gave the 6-methoxy-2,3,4,4a,5,10-hexahydrobenzo[ g ]quinoline-3-carboxylic acid·hydrochloride in high yield. The trans fusion of the two six-membered rings was established after NaBH 4 reduction. After esterification, n -propylation, and kinetic protonation of an intermittantly formed trimethylsilylketene acetal, the desired product was isolated in high yield and excellent purity.",10.1021/op0000531,2000-08-17,0.5929654523811313
Synthesis,"A New Route to 2,3,5-Trisubstituted 2,3-Dihydro-1,3,4-oxadiazoles via Stabilized Sulfuranes",,10.1055/s-1984-30902,1984-01-01,0.5929626732040122
Reaction Chemistry & Engineering,Assessing a sustainable manufacturing route to lapatinib,"A synthetic route to an anti-cancer drug, lapatinib, was devised to support the development of a sustainable manufacturing process in South Africa.",10.1039/d2re00267a,2022-01-01,0.5929626314828217
Journal of Organic Chemistry,Brief Total Synthesis of the Cell Cycle Inhibitor Tryprostatin B and Related Preparation of Its Alanine Analogue,"Tryprostatin B was synthesized in 32% overall yield from the readily available dipeptide anhydride cyclo-(l-Trp-l-Pro). Its tandem C-3 prenylation/cyclization gave the corresponding pentacyclic pyrroloindole systems bearing a prenyl group at the indole C-3 position. These compounds were then submitted to acid-catalyzed opening of the newly formed ring, with concomitant migration of the prenyl group to the indole C-2 position. The alanine analogue of tryprostatin B was also prepared using a similar sequence. The successful implementation of this strategy strengthens the case for a biosynthetic route for the tryprostatins along similar lines.",10.1021/jo034703l,2003-08-12,0.5929591775286381
Journal of the American Chemical Society,Total Synthesis of the Anticancer Natural Product OSW-1,"The highly potent anticancer natural saponin OSW-1 has been successfully synthesized from commercially available 5-androsten-3beta-ol-17-one 79 in 10 operations with 28% overall yield. The key steps in the total synthesis included a highly regio- and stereoselective selenium dioxide-mediated allylic oxidation of 80 and a highly stereoselective 1,4-addition of alpha-alkoxy vinyl cuprates 68 to steroid 17(20)-en-16-one 12E to introduce the steroid side chain. This total synthesis demonstrated once again the versatile synthetic applications of alpha-halo vinyl ether chemistry developed in our laboratories.",10.1021/ja012119t,2002-05-17,0.5929583757463897
Tetrahedron,"Efficient synthesis of (±)-N-BOC-exo-2-(methoxycarbonyl)-7-Azabicyclo[2.2.1]heptane, a versatile intermediate for the synthesis of epibatidine and epiboxidine",,10.1016/s0040-4039(97)01606-7,1997-09-01,0.5929570353448574
Organic Letters,A Concise Synthesis of the Pentacyclic Framework of Cortistatins,"An efficient synthesis of the pentacyclic framework of cortistatins has been developed. The key strategy comprises assembly of the A- and the CD-ring fragments by Knoevenagel reaction, facile formation of the pyran ring via electrocyclization, and construction of the seven-membered B-ring by radical addition to an alpha,beta-unsaturated ketone.",10.1021/ol8012099,2008-07-17,0.5929569466939835
Journal of Organic Chemistry,Humilisin E: Strategy for the Synthesis and Access to the Functionalized Bicyclic Core,"High Resolution Image Download MS PowerPoint Slide Humilisin E is a diterpenoid possessing a rare epoxidized cyclononene trans -fused with a bicyclo[3.2.0]heptane core. We have identified the P atropisomer of the corresponding cyclononadiene as a potential biosynthetic/synthetic precursor to humilisin E and reported two different strategies for the stereocontrolled synthesis of the appropriately functionalized bicyclic cores of humilisin E. The first route involves a Stork epoxynitrile cyclization via a Mg alkoxide, and the second, more stereoselective approach utilizes the Wolff rearrangement as the key step.",10.1021/acs.joc.4c00358,2024-04-26,0.5929546579797459
Journal of the American Chemical Society,Efficient Enantioselective Syntheses of (+)-Dalesconol A and B,"We herein report the first enantioselective syntheses of immunosuppressants (+)-dalesconol A and B in a highly efficient and concise manner, which features an efficient palladium-catalyzed enantioselective dearomative cyclization-kinetic resolution cascade to install the chiral all-carbon quaternary center, an effective sterically hindered Stille coupling, a powerful 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) oxidation to furnish all requisite unsaturation, and a tandem hydrolysis-ring closure sequence.",10.1021/jacs.7b00783,2017-02-22,0.5929465330958649
Journal of Organic Chemistry,Total Synthesis of the Topopyrones:  A New Class of Topoisomerase I Poisons,"The topopyrones represent a new class of highly cytotoxic topoisomerase I poisons. Efficient total syntheses of all four naturally occurring members of this class have been accomplished. Key elements of the syntheses include Diels-Alder reactions employing two novel dienes and a titanium-mediated ortho-directed Friedel-Crafts acylation. Additionally, the syntheses of two chlorinated analogues accessible from an advanced intermediate are described.",10.1021/jo702487r,2008-01-10,0.5929457943600104
Organic Letters,Stereoselective Synthesis of (±)-Cephanolide B,"A concise and stereoselective total synthesis of (±)-cephanolide B was achieved in 15 steps. The key steps in the synthesis were as follows: (i) an intermolecular Diels–Alder reaction followed by lactonization to form the oxabicyclo[2.2.2]octane DE ring; (ii) a tandem reaction, featuring an intramolecular Pauson–Khand reaction, a 6π-electrocyclization, and an oxidative aromatization by O 2, to construct the ABC-tricyclic rings (6-5-6); and (iii) a phthaloyl peroxide-mediated arene oxygenation to install the C-13 phenol group.",10.1021/acs.orglett.1c03579,2021-11-16,0.5929457727021388
Angewandte Chemie International Edition,Enantioselective Copper‐Catalyzed Carboetherification of Unactivated Alkenes,"Chiral saturated oxygen heterocycles are important components of bioactive compounds. Cyclization of alcohols onto pendant alkenes is a direct route to their synthesis, but few catalytic enantioselective methods enabling cyclization onto unactivated alkenes exist. Herein reported is a highly efficient copper-catalyzed cyclization of γ-unsaturated pentenols which terminates in C-C bond formation, a net alkene carboetherification. Both intra- and intermolecular C-C bond formations are demonstrated, thus yielding functionalized chiral tetrahydrofurans as well as fused-ring and bridged-ring oxabicyclic products. Transition-state calculations support a cis-oxycupration stereochemistry-determining step.",10.1002/anie.201402462,2014-05-05,0.5929351061982855
Synthesis,Stereoselective Formal Total Synthesis of (-)-Swainsonine from Garner's Aldehyde,A simple and facile stereoselective formal total synthesis of (-)-swainsonine has been reported starting from Garner’s l-serine derived oxazolidine aldehyde. Our synthetic strategy involves stereoselective allylation and Still olefination as key intermediary reaction steps.,10.1055/s-0030-1258418,2011-01-21,0.5929309513666339
Organic Letters,Tandem Radical Cyclizations with Iodoaryl Azides:  Formal Total Synthesis of (±)-Aspidospermidine,"An iodoazide radical cascade cyclization strategy has been used as the key step in a formal synthesis of aspidospermidine. Specifically, this step generated the alkaloid's B- and E-rings in the ethylidene-functionalized tetracycle 5. In turn, this was converted into pentacycle 25, a known advanced synthetic precursor of aspidospermidine.",10.1021/ol006477x,2000-10-13,0.5929300402469804
Journal of Organic Chemistry,Lactone-Directed Intramolecular Diels−Alder Cyclization:  Synthesis of <i>trans</i>-Dihydroconfertifolin,"Trienes 1 and 3 were obtained in five steps from ethyl 4-acetoxy-3-oxobutanoate and 6-iodo-3-methyl-1,3-hexadiene. Intramolecular Diels-Alder cyclization of 1 and 3 gave tricyclic lactones 2 and 4 as the major products, respectively. The key intermediate 4 was converted in two steps to trans-dihydroconfertifolin (5).",10.1021/jo020161g,2002-05-23,0.5929297338705208
Tetrahedron,Efficient conversion of sulfides into ester-stabilized ylids; alkene synthesis via ylid fragmentation,,10.1016/s0040-4039(00)71337-2,1976-09-01,0.5929277324263925
Reaction Chemistry & Engineering,Economic kilogram-scale synthesis of the novel antiepileptic drug brivaracetam utilizing porcine pancreatic lipase,Economic kilogram-scale synthesis of the novel antiepileptic drug brivaracetam involving an enzymatic hydrolysis by porcine pancreatic lipase was developed in nine steps starting from commercially available dimethyl 2-propylmalonate.,10.1039/d2re00524g,2023-01-01,0.5929118379860328
Synlett,A One-Step Synthesis of 5-Hydroxyflavones,"All articles of this category 5-hydroxy flavones were prepared in one step starting from 2,6-dihydroxyacetophenone. The latter was treated with an aroyl chloride in the presence of an excess of potassium carbonate to afford 5-hydroxyflavones. 5-hydroxyflavones - one-step synthesis",10.1055/s-1999-2844,1999-09-01,0.5929045887720558
Synthesis,Tungsten-Promoted Hetero-Pauson–Khand Cycloaddition: Application to the Total Synthesis of (–)-Allosecurinine,"Herein, we report a concise enantioselective synthesis of (–)-allosecurinine, a tetracyclic Securinega alkaloid featuring an α,β-unsaturated γ-lactone moiety. Starting from inexpensive and readily available trans-l-hydroxyproline, our strategy entails a rare late-stage [2+2+1]-hetero-Pauson–Khand cycloaddition between a ketone and an alkyne as the key complexity-generating step to rapidly install the CD-ring system. The reported W(CO)6-promoted intramolecular cyclization provides the first example of a tungsten-mediated hetero-Pauson–Khand reaction. This approach to the strained bicyclic CD motif present in ­allosecurinine provides some insights into the boundaries of this potentially powerful methodology that might be further extended to other butenolide-containing natural products.",10.1055/s-0037-1612063,2019-02-18,0.5929014261166783
Tetrahedron,Preparation of a deoxynucleoside thiophosphoramidite intermediate in the synthesis of nucleoside phosphorodithioates,,10.1016/s0040-4039(00)88455-5,1988-01-01,0.5929002266316807
European Journal of Organic Chemistry,The Enantioselective Formal Synthesis of (+)-Avenaciolide and (+)-Isoavenaciolide from Tri-O-acetyl-D-glucal Using a Ring Contraction Reaction as the Key Step,"We describe a formal synthesis of (+)-avenaciolide and (+)-isoavenaciolide starting from methyl tri-O-acetyl-D-glucal. The key steps are a ring-contraction reaction of compound 8 to give the bicyclo 6, and the oxidation of the diol 9 to give the bis-lactone framework.",10.1002/1099-0690(200006)2000:12<2285::aid-ejoc2285>3.0.co;2-8,2000-06-01,0.5928985166445154
Journal of Organic Chemistry,Synthesis of Acyclic Nucleosides with a Chiral Amino Side Chain by the Mitsunobu Coupling Reaction,A novel and efficient synthetic method has been developed for the preparation of chiral acyclic nucleosides with a chiral amino side chain by Mitsunobu reaction between nucleoside bases and protected L-serine. This method suggests a potentially more efficient and complementary process to acquire chiral acyclic nucleosides.,10.1021/jo100397a,2010-04-30,0.5928963301409829
Organic Process Research & Development,Some Items of Interest to Process R&amp;D Chemists and Engineers,"have reported a straightforward synthesis of 5-amino-6-oxo-2-phenyl-1-pyrimidineacetic acid, an important core molecule for the preparation of nonpeptidic enzyme inhibitors.Thus, treatment of hippuric acid (R = H) with triethyl orthoformate afforded the intermediate oxazolone in good yield; subsequent treatment with an N-(carboxy",10.1021/op300191p,2012-08-01,0.5928960009032637
Organic Letters,"Total Synthesis of an All-1,2-<i>cis</i>-Linked Repeating Unit from the <i>Acinetobacter baumannii</i> D78 Capsular Polysaccharide","High Resolution Image Download MS PowerPoint Slide Chemical synthetic efforts have resulted in the preparation of the assigned tetrasaccharide repeating subunit from the Acinetobacter baumannii KL4-associated capsular polysaccharide. A convergent synthetic strategy hinging on a 1,2- cis -selective [2+2] glycosylation to generate the fully protected tetrasaccharide was key to the success of this synthesis.",10.1021/acs.orglett.2c01034,2022-05-06,0.5928944390657516
Tetrahedron,An efficient total synthesis of the anticancer agent (+)-spisulosine (ES-285) from Garner’s aldehyde,,10.1016/j.tetlet.2010.05.146,2010-06-03,0.5928775578873626
Synlett,The Synthesis of 1′-Methyl Carbocyclic Thymidine and its Effect on Nucleic Acid Duplex Stability,"All articles of this category The enantioselective synthesis of the title compound 1 has been accomplished in 18 chemical steps starting from cyclopentadiene via epoxide 2 and amine 9 as the central key intermediates. Oligodeoxyribonucleotides incorporating several modified building blocks 1 are still capable of hybridizing to complementary RNA, albeit with lower affinity than their natural counterparts.",10.1055/s-1994-23030,1994-01-01,0.5928759527020135
Synthesis,"Asymmetric Synthesis of (<i>S</i>,<i>S</i>)- and (<i>R</i>,<i>R</i>)-2-Methylthreitol","The asymmetric synthesis of (S,S)- and (R,R)-2-methylthreitol was carried out, starting from the SAMP or RAMP hydrazone of 2,2-dimethyl-1,3-dioxan-5-one. The protocol involves an enantioselective α-alkylation as a key step. The second stereogenic center was installed by either nucleophilic 1,2-addition or diastereo­selective epoxidation with bis(acetylacetonato)oxovanadium(IV) [VO(acac)2] as catalyst. The title compounds were obtained in excellent diastereo- and enantiomeric excesses (≥98% de, 98% ee) and in good overall yields (40-61%).",10.1055/s-2007-965967,2007-03-27,0.592873552219178
Angewandte Chemie International Edition,A Novel Approach for the One-Pot Preparation of α-Amino Amides by Pd-Catalyzed Double Carbohydroamination,"A new domino reaction sequence, a palladium-catalyzed double carbohydroamination, which involves double carbonylation, amine condensation, and hydrogenation from an aryl iodide (1), a primary amine (2), and synthetic gas has been realized as a novel synthetic means for the one-pot synthesis of α-amino amides (3).",10.1002/1521-3773(20010216)40:4<779::aid-anie7790>3.0.co;2-1,2001-02-15,0.5928727847459934
Synlett,"Highly Brominated Norbornanes by Photobromination as Precursors for the Convenient Synthesis of 2,3,5,6-Tetrabromo- and 2,3,5,6-Tetramethoxy-substituted Norbornadienes","An efficient synthesis is described for hexabromonorbornane by photobromination of norbornadiene. Double dehydrobromination of the hexabromide by t-BuOK affords in high yield 2,3,5,6-tetrabromonorbornadiene, its copper-assisted treatment with sodium methoxide leads to the 2,3,5,6-tetramethoxy derivative. The tetrabromide constitutes a valuable precursor for the preparation of functionalized tetrasubstituted norbornadienes.",10.1055/s-2002-19330,2002-01-01,0.5928714885759988
Tetrahedron,"A short synthesis of an indolocarbazolyl-oxazol-2-one, a potential protein kinase C inhibitor",,10.1016/0040-4039(95)94696-p,1995-04-01,0.5928697844984261
Journal of Organic Chemistry,Efficient and Regioselective Synthesis of 2-Alkyl-2<i>H</i>-indazoles,An efficient and regioselective synthesis of 2-methyl-2H-indazoles and 2-ethyl-2H-indazoles using trimethyloxonium tetrafluoroborate or triethyloxonium hexafluorophosphate is reported.,10.1021/jo0265434,2003-04-16,0.5928655974524472
Journal of Organic Chemistry,Palladium-Catalyzed Direct (Hetero)arylation of Ethyl Oxazole-4-carboxylate: An Efficient Access to (Hetero)aryloxazoles,"A straightforward route toward 2-(hetero)arylated and 2,5-di(hetero)arylated oxazoles through regiocontrolled palladium-catalyzed direct (hetero)arylation of ethyl oxazole-4-carboxylate with iodo-, bromo-, and chloro(hetero)aromatics followed by a two-step hydrolysis/decarboxylation sequence was described. The method was applied here to a neat synthesis of two 2,5-di(hetero)aryloxazole natural products, balsoxin and texaline.",10.1021/jo801093n,2008-08-15,0.5928650549228457
Journal of Organic Chemistry,"A Regio- and Diastereoselective Intramolecular Nitrone Cycloaddition for Practical 3- and 2,3-Disubstituted Piperidine Synthesis from γ-Butyrolactone","A fast and efficient route for diversity-oriented synthesis of 3- and 2,3-disubstituted piperidines, featuring an intramolecular nitrone cycloaddition with high regio- and diastereoselectivity, was achieved in six steps and 36-66% overall yield from commercially available gamma-butyrolactone or 1,4-butanediol. A new N-alkenyl nitrone enoate was used in this intramolecular nitrone cycloaddition, and the regioselectivity, diastereoselectivity, and reversibility of this cycloaddition were investigated.",10.1021/jo8018285,2008-11-24,0.5928640702986174
Synthesis,"An Improved Synthesis of 2,3-Norbornadienoanthracene and its Application to the Synthesis of Anthracene Annellated Norbornenylogs","(opens in new window) Buy Article (opens in new window) Permissions and Reprints (opens in new window) All articles of this category (opens in new window) An improved synthesis of the title compound 1 is reported and involves the thermal cycloaddition of 1,4-naphthoquinone 3 to cyclopentadiene and subsequent treatment of the resulting adduct 4 with lithium aluminium hydride followed by tosyl chloride in pyridine. That 1 can provide access to a variety of anthracene annellated norbornyl compounds is exemplified by the synthesis of 9 through ruthenium-catalysed thermal cycloaddition of dimethyl acetylenedicarboxylate to 1 , followed by cycloaddition of quadricylane to the resulting adduct 8 .",10.1055/s-1986-31602,1986-01-01,0.5928631282062011
Organic Letters,A Concise Total Synthesis of Pyrovellerolactone Using a Rhodium-Catalyzed [(3 + 2) + 2] Carbocyclization Reaction,"A concise and highly convergent three-step total synthesis of the lactarane natural product, pyrovellerolactone, is described. The key step involves a regio- and diastereoselective rhodium-catalyzed [(3 + 2) + 2] carbocyclization of an alkenylidenecyclopropane with a 4-hydroxybut-2-ynoate followed by an in situ intramolecular lactonization to generate the tricyclic core in a single operation. This represents the first example of a higher-order [3 + 2 + 2] carbocyclization reaction in total synthesis, which is likely to provide an important strategy for the construction of related targets within this sesquiterpene family.",10.1021/ol400165x,2013-03-29,0.5928606555624336
Tetrahedron,"An efficient synthesis of (2S,3R)-3-hydroxylysine via ruthenium catalyzed asymmetric hydrogenation",,10.1016/s0040-4039(98)01387-2,1998-09-01,0.5928465041913716
Tetrahedron,"New and efficient synthesis of (E)-4-diethoxyphosphonyl-2-methyl-2-butenal and of ethyl (E)-4-diethoxyphosphonyl-2-methyl-2-butenoate, important building blocks in retinoid chemistry",,10.1016/0040-4039(94)02274-f,1995-01-01,0.5928390010171818
Tetrahedron,‘β-Acarbose’: A potential inhibitor of β-d-glucosidases and β-d-glucan hydrolases,,10.1016/0040-4039(96)00298-5,1996-04-01,0.592830410174834
Organic Letters,"Total Synthesis of (−)-Herbindoles A, B, and C via Transition-Metal-Catalyzed Intramolecular [2 + 2 + 2] Cyclization between Ynamide and Diynes","The total syntheses of (-)-herbindoles A, B, and C as naturally occurring forms were accomplished for the first time through transition-metal-catalyzed intramolecular [2 + 2 + 2] cyclization between ynamide and diynes. This strategy provided a highly efficient synthetic route to all three herbindoles from an identical indoline derivative as a common intermediate.",10.1021/ol300571b,2012-03-27,0.5928300731708753
Tetrahedron,Photoextrusion reactions: SO2 extrusion as a route to cyclophanes,,10.1016/s0040-4039(01)91421-2,1978-01-01,0.5928265442303249
Synthesis,Total Synthesis and Structure–Activity Relationship Studies of the Cytotoxic Anhydrophytosphingosine Jaspine B (Pachastrissamine),"By utilizing an l -serine-derived bicyclic lactone as an advanced chiral building block, a short synthetic route to the cytotoxic marine natural product jaspine B has been developed. Targeting structure–activity relationship investigations, the synthetic route has also been utilized for the synthesis and cytotoxicity evaluation of strategically modified jaspine B analogues. In addition, a previously reported synthesis of the title natural product from our research has been reinvestigated to clarify the sterochemical assignment.",10.1055/s-0036-1588118,2016-12-19,0.5928140190200972
Journal of Organic Chemistry,A Convergent Synthesis of the 11-Oxa Prostaglandin Analogue AL-12182,"[reaction: see text] The 11-oxa prostaglandin analogue AL-12182 1 has potent topical ocular hypotensive activity. A convergent and concise general synthesis of this class of prostanoid was developed employing a stereoselective coupling reaction between a tetrahydrofuran core electrophile and a nucleophilic omega side chain component, providing a route that should be suitable for commercial scale production. The tetrahydrofuran core was assembled from dimethyl d-malate using a stereoselective beta-hydroxy ester dianion alkylation reaction.",10.1021/jo048035v,2005-01-26,0.5928125469084075
Tetrahedron,A novel short and efficient asymmetric synthesis of statine analogues,,10.1016/s0040-4039(00)86044-x,1988-01-01,0.5928094762625772
Synlett,Total Synthesis of (<i>R</i>)-(+)-Kavain via (MeCN)<sub>2</sub>PdCl<sub>2</sub>-Catalyzed Isomerization of a<i>cis</i>Double Bond and Sonochemical Blaise Reaction,"From the chiral source 2,3-O-isopropylidene-d-glyceraldehyde 2, the natural product (R)-(+)-kavain 1a was efficiently synthesized in a total yield of 25% via (MeCN)2PdCl2-catalyzed isomerization of the cis double bond of an olefin as the key step and sonochemical Blaise reaction. The chiral center adjacent to the cis double bond was retained without protection of the free allylic hydroxy during the isomerization process.",10.1055/s-2005-871953,2005-01-01,0.5927990402514951
Angewandte Chemie International Edition,"Stereocontrolled Total Syntheses of (−)‐Rotenone and (−)‐Dalpanol by 1,2‐Rearrangement and S<sub>N</sub>Ar Oxycyclizations","Abstract The total syntheses of (−)‐rotenone and (−)‐dalpanol have been achieved by a group‐selective, stereospecific 1,2‐shift of an epoxy alcohol and S N Ar cyclizations. Three oxacycles are constructed, thus illustrating a versatile synthetic route to various rotenoids.",10.1002/anie.201609253,2016-12-02,0.5927978746371552
Synthesis,"Synthesis of 1<i>H</i>-2-Benzopyran-5,8-dione Derivatives from 2-(1-Hydroxyalkyl)-1,4-benzoquinones and Enamines","An efficient synthesis of the title benzopyranodione derivatives based on a Michael addition/cyclization sequence between 2-(1-hydroxyalkyl)-1,4-benzoquinones and enamines (or an imine) is described.",10.1055/s-2003-38066,2003-01-01,0.592794739760898
Tetrahedron,"Synthesis of ambergris fragrance chemicals from sclareol, involving palladium catalysed key steps",,10.1016/0040-4039(88)85323-1,1988-01-01,0.5927927485781651
Tetrahedron,An efficient synthesis of optically pure anthracyclinone intermediates by the novel use of microbial reduction,,10.1016/s0040-4039(00)88665-7,1982-01-01,0.5927798321386915
Tetrahedron,A convergent approach for the total synthesis of (−)-synrotolide diacetate,,10.1016/j.tetlet.2007.07.172,2007-08-01,0.5927711884821071
Tetrahedron,A convergent approach to the formal total synthesis of hemibrevetoxin B,,10.1016/j.tetlet.2006.11.058,2006-11-30,0.5927711884821071
Tetrahedron,"A novel reductive cyclization involving attack by an oxime on an unconjugated alkyne, a new route to 4-aza sterols.",,10.1016/s0040-4039(01)99837-5,1983-01-01,0.5927571464982487
Organic Letters,Short Synthesis of the C1−C14 Stretch of Discodermolide from Building Blocks Prepared by Asymmetric Catalysis,"A convergent and stereoselective synthesis of the C1-C14 stretch of (+)-discodermolide demonstrates the utility of the ""asymmetric catalysis approach"" to complex polypropionates. The preparation of this complex synthon requires 15 steps in the longest linear sequence and 19 steps total from inexpensive materials.",10.1021/ol7029933,2008-03-01,0.5927567491705406
Organic Letters,"Preliminary Studies on the Transformation of Nitrosugars into Branched Chain Iminosugars:  Synthesis of 1,4-Dideoxy-4-<i>C</i>-hydroxymethyl- 1,4-imino-pentanols","A novel promising strategy for the transformation of nitrosugars into branched pyrrolidines, based on double Henry reaction with formaldehyde followed by reductive ring closure, allowed the first enantiospecific synthesis of a 4-C-hydroxymethyl branched derivative of the well-known glycosidase inhibitor 1,4-dideoxy-1,4-imino-pentanol. This strategy also afforded a new route to some other interesting derivatives, such as N-hydroxy, N-propyloxy, and imino derivatives, a new kind of compounds with promising biological properties. [reaction: see text].",10.1021/ol062887v,2007-01-18,0.5927516395307381
Journal of Organic Chemistry,Total Synthesis of a Diacetonide Derivative of Thuggacin A,"A highly stereoselective total synthesis of the diacetonide derivative of the antibiotic thuggacin A has been described. The synthesis features the stereoselective Stille cross-coupling reaction to set up the whole carbon framework, aldol condensation to construct the highly substituted conjugated diene, non-Evans syn aldol, CBS reduction, Hantzsch's thiazole synthesis, Horner-Wadsworth-Emmons reaction, and Shiina's macrolactonization.",10.1021/acs.joc.5b02426,2016-02-09,0.5927385634220296
Journal of Organic Chemistry,A Stereoselective Cyclization Strategy for the Preparation of γ-Lactams and Their Use in the Synthesis of α-Methyl-β-Proline,A straightforward stereoselective and enantiodivergent cyclization strategy for the construction of γ-lactams is described. The cyclization strategy makes use of chiral malonic esters prepared from enantiomerically enriched monoesters of disubstituted malonic acid. The cyclization occurs with the selective displacement of a substituted benzyl alcohol as the leaving group. A Hammett study illustrates that the cyclization is under electronic control. The resulting γ-lactam can be readily converted into a novel proline analogue.,10.1021/jo3015903,2012-11-05,0.5927323833212149
Organic Letters,De Novo Formal Synthesis of (−)-Apicularen A via an Iterative Asymmetric Hydration Sequence,"[Structure: see text] A de novo approach to the formal total synthesis of the macrolide natural product (-)-apicularen A has been achieved in 18 steps from achiral starting materials. Both the absolute and relative stereochemistries of apicularen A were introduced by a Sharpless asymmetric dihydroxylation, a pi-allyl-palladium catalyzed reduction, a stereoselective reduction, and a base-promoted transannulation to install the C-9 stereocenter.",10.1021/ol062595u,2006-11-29,0.5927243549572
Organic Letters,"Biomimetic Total Synthesis of Rhodonoids C and D, and Murrayakonine D","A divergent, three-step total synthesis of rhodonoids C and D has been achieved using a biosynthetically inspired, acid-catalyzed cascade cyclization of an epoxy-chromene that involves the presumed intermediacy of o-quinone methides. Application of a similar strategy also allowed synthesis of the alkaloid murrayakonine D.",10.1021/acs.orglett.7b00779,2017-05-03,0.5927232673967999
Organic Letters,A General Approach to the Synthesis of 1-Deoxy-<scp>l</scp>-iminosugars,"A stereoselective procedure for the preparation of non-naturally occurring deoxy iminosugars belonging to L-series has been developed. The synthesis involves the construction of the key intermediate bicycle pyperidine 8, available in few steps by the coupling of the heterocyclic synthon 3 and the readily available Garner aldehyde 4.",10.1021/ol7014847,2007-07-20,0.5927168861847218
Journal of Organic Chemistry,Synthesis of α-<scp>l</scp>-Threose Nucleoside Phosphonates via Regioselective Sugar Protection,"A new synthesis route to α-L-threose nucleoside phosphonates via 2-O and 3-O selectively protected L-threose is developed. The key intermediates 2-O-benzoyl-L-threonolactone and 1-O-acetyl-2-O-benzoyl-3-O-t-butyldiphenylsilyl-L-threofuranose were functionalized to synthesize 2'-deoxy-2'-fluoro- and 3'-C-ethynyl L-threose 3'-O-phosphonate nucleosides. The key intermediates developed are important intermediates for the synthesis of new L-threose-based nucleoside analogues, TNA phosphoramidites, and TNA triphosphates.",10.1021/jo400907g,2013-07-03,0.5927148958150988
Journal of Organic Chemistry,"Electrophilic Cyclization and Intermolecular Acetalation of 2-(4-Hydroxybut-1-yn-1-yl)benzaldehydes: Synthesis of Diiodinated Diepoxydibenzo[<i>c</i>,<i>k</i>][1,9]dioxacyclohexadecines","An expedient strategy for the preparation of diiodinated diepoxydibenzo[c,k][1,9]dioxacyclohexadecines from readily available 2-(4-hydroxybut-1-yn-1-yl)benzaldehydes through electrophile-triggered tandem cyclization/intermolecular acetalation sequence has been presented. The electrophilic macrocyclization can be performed under mild conditions and in up to gram quantities. Moreover, palladium-catalyzed coupling and reduction reactions of the resulting iodides could efficiently afford oxa-macrocycles.",10.1021/acs.joc.7b01646,2017-09-01,0.5927132773302352
Journal of the American Chemical Society,Total Synthesis of (−)-Mandelalide A Exploiting Anion Relay Chemistry (ARC): Identification of a Type II ARC/CuCN Cross-Coupling Protocol,"Anion relay chemistry (ARC), an effective, multicomponent union tactic, was successfully employed for the total synthesis of the highly cytotoxic marine macrolide (-)-mandelalide A (1). The northern hemisphere was constructed via a new type II ARC/CuCN cross-coupling tactic, while the southern hemisphere was secured via a highly efficient four-component type I ARC union. Importantly, the synthesis of 1 showcases ARC as a rapid, scalable coupling strategy for the union of simple readily available building blocks to access diverse complex molecular fragments with excellent stereochemical control.",10.1021/jacs.6b01731,2016-03-08,0.5927051849127558
Green Chemistry,Enantioselective chemoenzymatic synthesis of a key segment of neuronal nitric oxide synthase inhibitors and several related 3-aminopyridinylmethyl-4-hydroxypyrrolidines,High enantioselective lipase catalyzed resolution of several <italic>cis</italic> and <italic>trans</italic> 3-aminopyridinylmethyl-4-hydroxypyrrolidines has been described. Some of these pyrrolidines are precursors in the synthesis of selective nNOS inhibitors.,10.1039/c6gc01965j,2016-08-31,0.5927037605027841
Tetrahedron,A novel approach for total synthesis of cryptophycins via asymmetric crotylboration protocol,,10.1016/s0040-4039(98)01994-7,1998-11-01,0.5926999008308808
Journal of the American Chemical Society,Palladium-Catalyzed Enantioselective Domino Heck/Intermolecular C–H Bond Functionalization: Development and Application to the Synthesis of (+)-Esermethole,"Intramolecular asymmetric carbopalladation of N-aryl acrylamides followed by intermolecular trapping of the resulting σ-C(sp(3))-Pd complex by azoles afforded 3,3-disubstituted oxindoles in good yields with excellent enantioselectivities. Two C-C bonds were created with concurrent formation of an all-carbon quaternary stereocenter. Oxadiazole substituted oxindoles were subsequently converted to pyrroloindolines by an unprecedented reductive cyclization protocol. The utility of this chemistry was illustrated by an enantioselective synthesis of (+)-esermethole.",10.1021/jacs.5b11625,2015-12-17,0.592692167776512
Tetrahedron,Synthesis of the glucoallosamidin pseudo-disaccharide: Use of an efficient Hg(II) mediated cyclization,,10.1016/0040-4039(95)02230-9,1996-01-01,0.5926918161340141
Journal of the American Chemical Society,An Expeditious Total Synthesis of (±)-Stenine,(+/-)-Stenine was synthesized in eight steps from a known ketophosphonate reagent. The key step was an exo-selective Diels-Alder/intramolecular Schmidt domino reaction that afforded three of the four rings and four stereocenters in a single reaction.,10.1021/ja055629m,2005-10-22,0.59268966746775
Organic Letters,Investigating Biogenetic Hypotheses of the <i>Securinega</i> Alkaloids: Enantioselective Total Syntheses of Secu’amamine E/<i>ent</i>-Virosine A and Bubbialine,"The synthesis of the Securinega alkaloid secu'amamine E (ent-virosine A) has been accomplished for the first time in 12 steps and 8.5% overall yield. In addition, bubbialine has been prepared and characterized. These two alkaloids and bubbialidine, all featuring an azabicyclo[2.2.2]octane core, were rearranged to their azabicyclo[3.2.1]octane congeners, a framework found in many Securinega alkaloids. These experiments suggest that azabicyclo[2.2.2]octane derivatives could serve as intermediates in the biosynthesis of the rearranged azabicyclo[3.2.1]octane products.",10.1021/acs.orglett.6b03716,2017-01-17,0.5926880633600152
European Journal of Organic Chemistry,Preparation and Synthetic Applications of [2.2]Paracyclophane Trifluoroborates: An Efficient and Convenient Route to Nucleophilic [2.2]Paracyclophane Cross‐Coupling Building Blocks,"We report the synthesis of [2.2]paracyclophane (PCP) trifluoroborate building blocks that can be used for the incorporation of the PCP moiety into a wide range of (hetero)aryl chlorides, bromides and triflates by a Pd(II)/RuPhos mediated Suzuki–Miyaura cross‐coupling reaction. The PCP trifluoroborate species are bench stable with extended shelf life and easily accessible on a multigram scale by a two‐step synthesis from commercially available PCP. They can be handled conveniently without special precautions, thus overcoming many of the limitations of other PCP cross‐coupling reagents. Additionally, a high yielding regioselective monolithiation/borylation protocol for the synthesis of pseudo‐ para and pseudo‐ ortho PCP halotrifluoroborates and their subsequent Suzuki–Miyaura cross‐coupling are described.",10.1002/ejoc.201901171,2019-08-15,0.5926858470074869
European Journal of Organic Chemistry,Efforts and Strategies for the Syntheses of Clavine‐Type Ergot Alkaloid Aurantioclavine,"Abstract Aurantioclavine, isolated by Kozlovskii from Penicillium aurantiovirens , is a unique member of the 3,4‐disubstituted indole alkaloids distinguished by an azepino[5,4,3‐ cd ]indole. As an essential intermediate in the biosynthesis of the complex polycyclic alkaloids of the fungal communesin, it has attracted considerable attention as a synthetic target. The development of various synthetic strategies for their application in total synthesis has been described. An overview focused on the synthesis of aurantioclavine from its first synthesis to the most recent one is present.",10.1002/ejoc.202201000,2022-10-28,0.5926857495976062
Organic Letters,Asymmetric Synthesis of Unsaturated Monocyclic and Bicyclic Nitrogen Heterocycles,"Hydrolysis of scalemic trichloroacetamides Cl(3)CCONHCH(R)CHCH(2) and allylation, or acylation with but-3-enoic acid, followed by ring-closing metathesis resulted in the formation of unsaturated pyrrolidine and piperidine building blocks. These were employed in the synthesis of (S)-coniine (R = Pr) and a formal synthesis of (+)-anisomycin (R = p-MeOC(6)H(4)). Extension of this methodology with R = CH(2)CHCH(2) employing two ring-closing metatheses resulted in the synthesis of unsaturated quinolizidinone and indolizidinone frameworks.",10.1021/ol900880w,2009-05-29,0.5926849717564787
Journal of Organic Chemistry,"Enantioselective Total Synthesis and Assignment of the Absolute Configuration of the Furo[3,2-<i>a</i>]carbazole Alkaloid Furoclausine-B","We describe the first enantioselective total synthesis and the assignment of the absolute configuration of the furo[3,2- a]carbazole alkaloid furoclausine-B. As key steps for our approach we used a palladium(II)-catalyzed double C-H-bond activation for the construction of the carbazole framework, a Shi epoxidation, and an intramolecular opening of the epoxide for annulation of the dihydrofuran moiety.",10.1021/acs.joc.8b02426,2018-11-28,0.5926845880579222
Journal of Organic Chemistry,"Total Syntheses of (−)-Deoxoapodine, (−)-Kopsifoline D, and (−)-Beninine","alkaloids (-)-deoxoapodine, (-)-kopsifoline D, and (-)-beninine are described through a domino deprotection-Michael addition-nucleophilic substitution protocol to assemble the core framework in efficient steps. Corey-Bakshi-Shibata reduction was employed to afford the enantioenriched intermediate for the total syntheses of the aforementioned alkaloids. The chirality was shown to completely transfer to the backbone using Johnson-Claisen rearrangement. The enantioselective total syntheses of (-)-kopsifoline D and (-)-beninine were accomplished for the first time. Our strategy opens up practical avenues for the total synthesis of structurally similar alkaloids.",10.1021/acs.joc.9b02918,2019-12-13,0.5926833832658522
Organic Letters,Synthesis of the Integrastatin Nucleus Using the Ramberg−Bäcklund Reaction,"[reaction: see text] The first synthesis of the tetracyclic nucleus of the Integrastatins, natural products that have been shown to selectively inhibit HIV-1 integrase, is reported. Key steps of this synthesis involve a novel cis-selective Ramberg-Bäcklund reaction and an unusual Lewis acid-promoted cyclization step.",10.1021/ol035786v,2003-10-11,0.5926798555013145
Tetrahedron,Efficient synthesis of enantiomeric pairs of thiolactomycin and its 3-demethyl derivative,,10.1016/j.tetlet.2006.02.058,2006-03-04,0.5926786545277675
Tetrahedron,Synthesis of the core ring system of awajanomycin from N-Boc-3-methoxycarbonyl-2-pyridinone,,10.1016/j.tetlet.2009.02.141,2009-02-26,0.5926697396791679
Angewandte Chemie International Edition,Ruthenium(II)‐Catalyzed Asymmetric Inert C−H Bond Activation Assisted by a Chiral Transient Directing Group,"A ruthenium(II)-catalyzed asymmetric intramolecular hydroarylation assisted by a chiral transient directing group has been developed. A series of 2,3-dihydrobenzofurans bearing chiral all-carbon quaternary stereocenters have been prepared in remarkably high yields (up to 98 %) and enantioselectivities (up to >99 % ee). By this methodology, a novel asymmetric total synthesis of CB2 receptor agonist MDA7 has been successfully developed.",10.1002/anie.201913733,2019-12-23,0.5926661297575107
Synthesis,Coccidiostatic Agents: Synthesis of some Analogs of (±)-Frenolicin B,"All articles of this category Starting from juglone derivative 5 , a series of frenolicin B analogs 15 (R 1 = R 2 = Me), 19a (R 1 = H, R 2 = Ph), and 19b (R 1 = Ph, R 2 = H) were obtained via the key β -hydroxy ester intermediate 10 in a twelve step synthesis. coccidiosis - frenolicin B - β -hydroxy-ester - pyronaphthoquinone - γ -lactonisation",10.1055/s-1995-3992,1995-07-01,0.5926624417046878
Journal of Organic Chemistry,Synthesis of 4-Aryl-2-pyrrolidones and β-Aryl-γ-amino-butyric Acid (GABA) Analogues by Heck Arylation of 3-Pyrrolines with Arenediazonium Tetrafluoroborates. Synthesis of (±)-Rolipram on a Multigram Scale and Chromatographic Resolution by Semipreparative Chiral Simulated Moving Bed Chromatography,"We report herein a new, practical, and economic synthesis of the phosphodiesterase inhibitor Rolipram on a multigram scale as well as the synthesis of new 4-aryl pyrrolidones and beta-aryl-gamma-amino butyric acids (GABA derivatives) employing an efficient Heck-Matsuda arylation of 3-pyrroline with aryldiazonium tetrafluoroborates. Racemic Rolipram was resolved into its enantiomers using chiral simulated moving bed chromatography having the low-cost microcrystalline cellulose triacetate as a chiral stationary phase.",10.1021/jo0484880,2005-01-06,0.5926619003237854
Tetrahedron,Syntheses without protection: a three-step synthesis of optically active clavicipitic acid by utilizing biomimetic synthesis of 4-bromotryptophan,,10.1016/s0040-4039(99)01620-2,1999-10-01,0.5926532218863357
Angewandte Chemie International Edition,Total Synthesis of (−)‐Indoxamycins A and B,"The concise total syntheses of (-)-indoxamycins A and B is reported. The chemistry features a seven-step preparation of a highly congested [5.5.6] tricyclic advanced common intermediate from a readily available R-carvone derivative. Key steps involve a Pauson-Khand reaction for the rapid construction of a basic scaffold bearing a quaternary carbon, a copper-catalyzed Michael addition for the introduction of another adjacent all-carbon quaternary stereocenter, and a tandem retro-oxa-Michael addition/1,2-addition/oxa-Michael addition for the installation of a trisubstituted olefin side chain. This synthetic strategy allows for easy access to both enantiomers of this family of natural products and their analogues from cost-effective starting material through straightforward chemical transformations.",10.1002/anie.201902043,2019-03-06,0.5926531380429585
Organic Letters,Total Synthesis of the <i>Illicium</i>-Derived Sesquineolignan Simonsol C,"The racemic form of the title natural product 1 has been synthesized by engaging, as a key step, the iodoarene-tethered cyclohexene 22 in an intramolecular Heck reaction to give compound 23. This angularly substituted tetrahydrodibenzo[b,d]furan was elaborated over a further five steps into target (±)-1.",10.1021/acs.orglett.6b01799,2016-07-11,0.5926465805422827
Tetrahedron,Selective synthesis of C32- and C20-monoiodinated chlorophyll derivatives,,10.1016/j.tetlet.2015.01.057,2015-01-13,0.5926465589799246
Tetrahedron,Selective synthesis of allenic and acetylenic derivatives via pentaorganylstiboranes,,10.1016/0040-4039(91)80226-v,1991-11-01,0.5926465589799246
Tetrahedron,"Asymmetric synthesis XI: A short synthesis of the chiral pyrrolidine synthon, 2-cyano-5-oxazolopyrrolidine",,10.1016/s0040-4039(00)61839-7,1987-01-01,0.5926464211951243
Angewandte Chemie International Edition,Stereoselective Total Synthesis of (+)‐Norrisolide,In a convergent approach to the marine natural product (+)-norrisolide (1) the two bicyclic ring systems are coupled through the C9C10 bond to assemble the carbon framework in a late stage of the synthesis. Other highlights of the synthetic strategy include the formation of the unusual fused γ-lactone–γ-lactol motif of 1 through a sequence of oxidation reactions.,10.1002/anie.200352868,2004-01-27,0.5926421433703949
Angewandte Chemie International Edition,Total Synthesis of Lankacyclinol,"An antitumor agent from various Streptomyces species, the title compound 1, has been synthesized for the first time, as described here. Key steps involved include a ring-closing metathesis, a photochemically induced acylnitrene insertion process, and highly selective Julia olefinations for the preparation of E,E diene moieties. The macrocycle was formed from an intramolecular Horner-Wadsworth-Emmons olefination induced by barium hydroxide.",10.1002/1521-3773(20001215)39:24<4612::aid-anie4612>3.0.co;2-c,2000-12-15,0.5926392170038426
Journal of Organic Chemistry,"Scalable Solution-Phase Synthesis of the Biologically Active Cyclodepsipeptide Destruxin E, a Potent Negative Regulator of Osteoclast Morphology","The scalable solution-phase synthesis of the cyclodepsipeptide destruxin E (1) has been achieved. Diastereoselective dihydroxylation of the terminal alkene in a 2-alkoxy-4-pentenoic amide, 7, was successfully accomplished utilizing (DHQD)2PHAL as the chiral ligand, and it was found that the use of the l-proline moiety in the substrate as a chiral auxiliary was essential for the induction of high diastereoselectivity to afford the key compound 4 on a gram scale. MNBA-mediated macrolactonization of 3 was also performed without formation of the dimerized product even under higher-dilution conditions, and it is noteworthy that the internal hydrogen bonds and s-cis configuration of the amide bond between N-methylalanine and N-methylvaline in the cyclization precursor 3 would assist in the macrolactonization to provide the macrolactone 2 without forming a dimerized product. Finally, epoxide formation in the side chain afforded destruxin E (1) on a gram scale in high purity (>98%).",10.1021/jo402437z,2013-11-19,0.5926373215245064
Tetrahedron,"Oxidative dimerization of 1,1-dimethyl-4-phenylsemicarbazide with lead tetraacetate: A novel route to the hexahydrotetrazine ring system",,10.1016/s0040-4039(01)88720-7,1969-01-01,0.5926368143867137
Tetrahedron,"Theonellamine B, a novel peptidal Na,K-atpase inhibitor, from an okinawam marine sponge of the genus Theonella.",,10.1016/s0040-4039(00)94264-3,1986-01-01,0.5926340315543277
Tetrahedron,"Ptilodene, a novel icosanoid inhibitor of 5-lifoxygenase and Na+/K+ ATPase from the red marine alga ptilota FilicinaJ. Agardh",,10.1016/s0040-4039(00)80336-6,1988-01-01,0.5926340315543277
Tetrahedron,"Corey lactone as key precursor for a facile synthesis of novel 1,2,3-triazole carbocyclic nucleosides via Click Chemistry",,10.1016/j.tetlet.2013.03.069,2013-03-24,0.5926317096575506
Synlett,"A Practical Way to 2,5-Disubstituted Pyrrolidine Derivatives","All articles of this category A novel route for the synthesis of 2,5-disubstituted pyrrolidines has been found through the allylation with allyltributyltin of N-acyliminium ion derived from N-protected pyroglutamic acid tert -butyl ester. Pyrrolidine - alkylation - acyliminium salt",10.1055/s-1996-5452,1996-05-01,0.592623605991586
Organic Letters,Formal Synthesis of Leustroducsin B via Reformatsky/Claisen Condensation of Silyl Glyoxylates,"A formal synthesis of leustroducsin B has been completed. The synthesis relies upon a recently developed Reformatsky/Claisen condensation of silyl glyoxylates and enantioenriched β-lactones that establishes two of the molecule's three core stereocenters and permits further elaboration to an intermediate in Imanishi's synthesis via reliable chemistry (Prasad reduction, asymmetric pentenylation, Mitsunobu inversion).",10.1021/ol2011192,2011-05-17,0.5926207525147531
Synlett,"SeO<sub>2</sub>-Mediated Oxidation of 1,3-Diazabuta-1,3-dienes: A Single-Pot Synthesis of Functionalized 4-Hydroxyimidazoles","A single-pot novel synthesis of variedly substituted 4-hydroxyimidazoles by SeO2-mediated oxidation of 1-aryl-2-phen­yl/thiomethyl/secondary amino-4-N,N-dimethylamino-4-methyl-1,3-diazabuta-1,3-dienes is reported.",10.1055/s-2006-949631,2006-09-01,0.5926205573217573
Synthesis,"Synthesis of New Chiral Mixed<i>cis</i>-Tetraheterodecalines by Highly Selective Cyclization of<i>N</i>,<i>N</i>′-Bisalkyl 2,3-Diaminobutanediols","Chiral secondary vic-diamines of diaminobutanediols have been efficiently prepared from l-tartaric acid. Their selective cyclization led to cis-tetraheterodecalines having a (1S,6S)-2,7-di­aza-4,9-dioxa[4.4.0]decane core system.",10.1055/s-2006-926389,2006-01-01,0.5926196535573856
Tetrahedron,A facile Garratt–Braverman cyclization route to intercalative DNA-binding bis-quinones,,10.1016/j.tetlet.2011.10.030,2011-10-25,0.5926085907918331
Tetrahedron,A catalytic and stoichiometric approach to the synthesis of the steroid B-ring en route to estratrienes,,10.1016/j.tetlet.2007.03.018,2007-03-13,0.5926071493223403
Organic Letters,Pd-Catalyzed Intermolecular Carbonylative Dearomatization of Arylamines with Propargylic Acetates for Synthesis of Bridged Polycyclic Lactams,"A new palladium-catalyzed multicomponent dearomatization of arylamines with CO and propargylic acetates for the synthesis of bridged polycyclic lactams is described. This method allows double annulation at the ipso and para positions of the amino group to form four new bonds, three C–C bonds and one C–N bond. DFT calculations and experimental studies indicate that the efficient formation of the allenecarboxanilide intermediate is the key step to achieve the dearomative transformation.",10.1021/acs.orglett.3c01344,2023-06-02,0.592603300790321
Synlett,Enantioselective Total Synthesis of 3-<i>epi</i>-Ottelione A,"An enantioselective total synthesis of (+)-3-epi-ottelione A (2), the earlier proposed stereostructure of the antitumor natural product ottelione A (4), was achieved for the first time starting from the known tetracyclic compound 9. The synthesis involves the following three crucial steps: (i) a coupling reaction of aldehyde 8 and aryllithium 7 to introduce the aromatic portion, (ii) base-induced lactol-opening/epimerization at the C1 position of 6 to deliver the requisite hydrindane 15, and (iii) Corey-Winter’s reductive olefination of the cyclic thiocarbonate 19 to install the C5-C6 double bond.",10.1055/s-2003-42114,2003-01-01,0.5926006421662405
Tetrahedron,Expedient route to CDE ring system of schintrilactones through tandem ROM–RCM of a norbornene derivative,,10.1016/j.tetlet.2010.03.074,2010-03-25,0.5926002880135622
Journal of Organic Chemistry,Short Total Synthesis of (+)-Colletotryptins B-D and Mucronatin B Derivative,"The short and first total synthesis of (+)-colletotryptins B-D, ent -colletotryptin A, and diastereomer of mucronatin B, which are a group of natural 3-(indol-2-yl)-3-(indol-3-yl)-1,2-propanediol (IIPDO) analogues containing two stereogenic centers at the C8′ and C9′ positions, isolated from endophytic fungus Colletotrichum sp. SC1355 and Tetrapterys mucronata, respectively, has been successfully accomplished in two and three steps with overall yields ranging from 28 to 54%. Key features of this synthesis include an innovative Bi(OTf) 3 -catalyzed stereoselective transindolylation of ( S )-3,3′-di(1 H -indol-3-yl)propane-1,2-diol. The operational simplicity, environmentally friendly catalyst, and broad functional group tolerance of this modular strategy render it suitable for adoption in both academic and industrial settings.",10.1021/acs.joc.4c00552,2024-05-29,0.5925925426042961
Synthesis,Synthesis of 2-Amino-5-hydroxycaprolactam Derivatives Mediated by E-Selective Olefination and Asymmetric Oxidation of the Enol Ether,"The asymmetric synthesis of 2-amino-5-hydroxycaprolactam derivatives is essential for exploring the antitumor properties of ester-bearing bengamides. In this study, chiral caprolactam isomers were achieved on the basis of highly E-selective Wittig olefination, asymmetric oxidations of the E-enol ethers, reductive amination of the aldehyde derivatives, cyclization of the 5-hydroxy­lysine analogues or/and deprotection.",10.1055/s-0030-1258275,2010-09-30,0.5925915310176958
Organic Letters,Total Synthesis of (−)-Colchicine via a Rh-Triggered Cycloaddition Cascade,"[reaction: see text] A synthesis of the antimitotic alkaloids (-)-colchicine and (-)-isocolchicine is reported. Important steps are (a) enantioselective transfer-hydrogenation of an alkynone, (b) iodine/magnesium exchange with subsequent aromatic acylation, (c) Rh-catalyzed transformation of an alpha-diazoketone into an oxatetracyclic key intermediate through intramolecular [3 + 2]-cycloaddition of an in situ generated carbonyl ylide, and (d) regioselective conversion of the cycloadduct into a tropolone derivative. The new synthetic strategy opens an efficient enantioselective access to colchicine and structural analogues.",10.1021/ol051316k,2005-09-01,0.5925907103276679
Tetrahedron,Ring isomerization of c-methyl isoflavones new syntheses of 2-hydroxy isoflavanones,,10.1016/s0040-4039(00)70559-4,1962-01-01,0.5925860677585142
Organic Letters,Synthesis of 1-Substituted Isoquinolines by Heterocyclization of TosMIC Derivatives: Total Synthesis of Cassiarin A,"A new method for the synthesis of 1-substituted isoquinolines by a heterocyclization that involves α-benzyl TosMIC derivatives and different electrophiles has been developed. This methodology has been successfully applied to a total synthesis of cassiarin A, an alkaloid with potent antiplasmodial activity against Plasmodium falciparum.",10.1021/acs.orglett.6b01521,2016-06-28,0.5925695909188752
Synthesis,An Efficient and Modular Route to C3*-TunePhos-Type Ligands,"An efficient and modular synthetic route to the bidentate C3*-TunePhos was developed, which allowed tunable steric and electronic effects of the ligands. This novel chemical technology highlights a versatile C3*-dibromodiphenyl intermediate that was accomplished by in situ Grignard exchange and subsequent Cu(II)-mediated intra­molecular oxidative radical coupling process. It is worth noting that this advanced intermediate not only could be easily prepared by a diverse array of C3*-TunePhos-type ligands, but also could be used to facile synthesis of other novel type of N,S-centered bidentate ligands.",10.1055/s-0036-1588421,2017-05-11,0.5925688606285036
Journal of Organic Chemistry,"Absolute Configuration Assignment by Asymmetric Syntheses of the Homalium Alkaloids (−)-(<i>R</i>,<i>R</i>,<i>R</i>)-Hoprominol and (−)-(4′<i>S</i>,4″<i>R</i>,2‴<i>R</i>)-Hopromalinol","The conjugate addition of lithium (R)-N-(3-chloropropyl)-N-(α-methylbenzyl)amide to α,β-unsaturated esters was used as the key step in the syntheses of all possible diastereoisomers of the homalium alkaloids hoprominol and hopromalinol. Comparison of the specific rotation data for these synthetic samples with those of samples isolated from the natural source enabled the absolute configurations within these alkaloids to be confidently assigned for the first time as (-)-(R,R,R)-hoprominol and (-)-(4'S,4″R,2‴R)-hopromalinol. The asymmetric syntheses of (-)-(R,R,R)-hoprominol (in 10 steps and 4.0% overall yield) and (-)-(4'S,4″R,2‴R)-hopromalinol (in 10 steps and 9.3% overall yield), from commercially available starting materials in each case, therefore represent the first total asymmetric syntheses of these alkaloids to be reported.",10.1021/jo301830j,2012-10-09,0.5925658452377305
Angewandte Chemie International Edition,Total Synthesis of (−)‐Spiroleucettadine,"One of a number of intriguing new alkaloids isolated from the Leucetta sp. sponge in 2004, spiroleucettadine displayed unique structural features on a restricted scaffold: a trans-fused 5,5-bicyclic ring system together with an amino hemiketal moiety. Attempts to synthesize the initially proposed structure failed, raising questions as to its veracity, and structure revision ensued in 2008; no successful synthetic approach has been reported to date. Herein, we describe the enantiospecific total synthesis of (-)-spiroleucettadine by a highly efficient biomimetic approach starting from l-tyrosine. One of two key hypervalent-iodine-mediated oxidation reactions forged the spirocyclic center, and the other enabled the installation of the methylamine side chain in the penultimate step. Our approach provides synthetic access to a new class of spiroannulated natural products and will enable future studies of the structure-biological-activity relationships of these antibacterial compounds.",10.1002/anie.201708110,2017-09-28,0.5925650900271471
Journal of Organic Chemistry,Total Syntheses of (−)-Mesembrane and (−)-Mesembrine <i>via</i> Palladium-Catalyzed Enantioselective Allylic Substitution and Zirconium-Promoted Cyclization,"4-Arylhexahydroindole derivatives 5 were synthesized from 2-arylcyclohexenyl allylamine derivatives 4, which have a large protecting group on nitrogen, using zirconium-promoted cyclization. Reaction of 4e with Cp(2)ZrBu(2), followed by treatment with MeMgBr and then O(2), gave 2a in 63% yield by a one-pot reaction, since the approach of O(2) to zirconium was prevented by the aryl group. The total syntheses of (+/-)-mesembrane and (+/-)-mesembrine were achieved starting from 2a. To synthesize these natural products in a chiral form, the starting allylamine derivative 24 (80% yield, 86% ee, recrystallized from MeOH, 99% ee with 79% recovery) was prepared from allyl carbonate 22a and N-tosylallylamine 23 using palladium-catalyzed asymmetric amination in the presence of (S)-BINAPO as a chiral ligand. (-)-Mesembrane and (-)-mesembrine were synthesized from this allylamine 24.",10.1021/jo9701187,1997-05-01,0.5925605759796515
Synlett,New Developments in the Synthesis of (E)-8-Styrylflavones,"A novel route for the synthesis of new ( E )-8-styrylflavones is reported. This methodology involves the regio- and stereoselective Heck cross-coupling reaction of 8-iodoflavones and styrene derivatives. The Heck precursors, 8-iodoflavones, were obtained through an efficient regioselective one-pot oxidative cyclization–iodination reaction of ( E )-2′-hydroxychalcones by applying the iodine/dimethyl sulfoxide system.",10.1055/s-0034-1380208,2015-05-04,0.5925588425347074
Organic Letters,Facile Preparation of Doubly Dipyrrolylquinoxaline-Bridged Expanded Porphyrins. Synthesis and Structural Characterization of an Unprecedented [20]Tetraphyrin-(2.1.2.1),[structure: see text] An unprecedented V-shape (2.1.2.1) expanded porphyrin incorporating an extended pi-conjugated system is described. Its efficient synthesis relied on the use of a new peralkyl tetrapyrrolylquinoxaline building block that constitutes the ideal intermediate for the versatile preparation of new quinoxaline-containing macrocycles.,10.1021/ol0606381,2006-05-01,0.5925579088938274
Organic Letters,Total Synthesis of (+)-Trachyspic Acid 19-<i>n-</i>Butyl Ester,"The first total synthesis of the alkyl citrate trachyspic acid 19- n -butyl ester ( 1 ) is described. A formal [2 + 2]-cycloaddition of the silylketene acetal derived from lactone 6 with di- n- butylacetylene dicarboxylate 7 provided the cyclobutene diester 5 with a dr >20:1. Acid-mediated rearrangement of 5 followed by lactone ring-opening and ester protecting group manipulation eventually provided orthogonally protected aldehyde 3 . A Nozaki–Hiyama–Kishi coupling between 3 and vinyl iodide 4 followed by oxidation of the resultant allylic alcohol gave enone 16, which was converted into the triester 17 (dr 6:1) by a spirocyclization/oxidative cleavage/elimination sequence. Removal of the t -butyl esters then afforded trachyspic acid 19- n -butyl ester ( 1 ).",10.1021/acs.orglett.0c00319,2020-02-17,0.5925551919390458
Synthesis,A New Route to [<i>g</i>]-Fused 5-Methyl-1-functionalized Isoquinolines,"All articles of this category 2-(3-Lithio-2-methoxy-4-pyridyl)-4,4-dimethyl-2-oxazoline ( 8 ) was condensed with aromatic aldehydes. Subsequent hydrolysis gave the corresponding lactones 10 . Reduction by ammoniacal zinc or calalytic hydrogenation of these compounds over palladium yielded 3-arylmethyl-2-pyridone-4-carboxylic acids 11 which were transformed into 3-arylmethy1-4-acetyl-2-pyridones 12 by methyllithium. Acidic ring closure then easily led to (g)-fused 5-methyl-2 H -isoquinoline-1-ones via a convergent pathway. This method is more rapid and convenient than former procedures reported for the synthesis of (g)-fused 5-methyl-1-functonalized isoquinolines.",10.1055/s-1987-27864,1987-01-01,0.5925535431971588
Organic Letters,Stereoselective Synthesis of the CDE Ring System of Antitumor Saponin Scillascilloside E-1,"A stereoselective synthesis of the CDE ring portion of the antitumor saponin scillascilloside E-1 has been achieved, utilizing an Ireland-Claisen rearrangement to construct the contiguous tetrasubstituted stereocenters at C13 and C17 simultaneously and intramolecular nitrile oxide cycloaddition to form the five-membered ring as key steps.",10.1021/ol500657f,2014-03-20,0.5925427692005633
Synthesis,A New Synthesis of<i>cis</i>-Chrysanthemic Acid,,10.1055/s-1982-29786,1982-01-01,0.5925314705304908
Organic Letters,Benzothiazines in Synthesis. A Total Synthesis of Pseudopteroxazole,"An enantioselective total synthesis of the naturally occurring antitubercular agent pseudopteroxazole is described. The synthesis is organized around the use of a stereoselective, intramolecular addition of a sulfoximine carbanion to an alpha,beta-unsaturated ester to form an enantiomerically pure benzothiazine. Other important processes include a completely stereoselective intramolecular Friedel-Crafts alkylation and a stereoselective and regioselective hydrogenation. [structure: see text]",10.1021/ol0515412,2005-07-15,0.5925288161257825
Organic Letters,Total Synthesis of Batzelladine D,"[structure: see text] Stereoselective total synthesis of batzelladine D was accomplished in 15 steps. This synthesis features (i) successive 1,3-dipolar cycloaddition reactions to form the 2,5-disubstituted pyrrolidine ring system, (ii) esterification of the side chain to the bicyclic guanidine carboxylate, a common synthetic intermediate of batzelladine alkaloids, and (iii) tricyclic guanidine formation under the Mitsunobu reaction conditions.",10.1021/ol026303a,2002-07-30,0.592525020754456
Tetrahedron,Diastereoselective synthesis of 4-hydroxycyclopentenones from (3-alkoxycarbonyl-2-oxo-propylidene)triphenylphosphorane and chiral glyoxals,,10.1016/0040-4039(95)00662-v,1995-05-01,0.5925112495607241
Organic Letters,A Stereoselective Synthesis of the C10−C31 (BCDEF Ring) Portion of Pinnatoxin A,[reaction: see text] An efficient synthesis of the C10-C31 (BCDEF ring) portion of pinnatoxin A has been achieved. The key step is a highly stereoselective construction of the dispiroketal (BCD ring) system employing an intramolecular hetero-Michael reaction of a reversibly formed hemiketal alkoxide through the use of LiOMe.,10.1021/ol0168364,2001-11-14,0.5925058095773201
Organic Process Research & Development,A New and Improved Process for Celiprolol Hydrochloride,"Celiprolol hydrochloride, a β-blocker drug, has been synthesized by a new approach. How this new process offers distinctive advantages over the existing one will be described.",10.1021/op000297l,2001-01-06,0.5925030328649084
Journal of Organic Chemistry,Novel and Stereocontrolled Synthesis of (±)-Tetrodotoxin from<i>m</i><i>yo</i>-Inositol,"[reactions: see text] The novel and stereocontrolled synthesis of (+/-)-tetrodotoxin from myo-inositol is described. The key steps involve the stepwise oxidation of hydroxyl groups to the carbonyl function, followed by the addition of specific nucleophiles, including the successive spiro alpha-chloroepoxide formation and its ring-opening with the azide anion, to give the desired branched chain structures (5-->6, 17-->18-->19-->20 and 23-->24-->25) with the desired regio- and stereoselectivities in high yields. The stepwise conversion of the alpha-azido aldehyde 25 to the delta-lactone 29, followed by reduction of the azide, introduction of a guanidine moiety, aldehyde formation, and deprotection, produced the (+/-)-tetrodotoxin.",10.1021/jo050342t,2005-08-16,0.592493816433935
Tetrahedron,"Highly efficient and regioselective synthesis of keto-enamine Schiff bases of 7-hydroxy-4-methyl-2-oxo-2H-benzo[h]chromene-8,10-dicarbaldehyde and 1-hydroxynaphthalene-2,4-dicarbaldehyde",,10.1016/j.tetlet.2007.01.044,2007-01-14,0.5924902018495782
Organic Letters,Enantioselective Synthesis of 15-<i>e</i><i>pi</i>-Haterumalide NA Methyl Ester and Revised Structure of Haterumalide NA,"[structure: see text] The enantioselective synthesis of the enantiomer of the haterumalide NA methyl ester, a cytotoxic macrolide from an Okinawan sponge, was achieved from the threitol derivative in 26 steps. The key steps are the stereoselective construction of a chloroolefin unit and the intramolecular Reformatsky-type reaction. This synthesis revised the absolute stereochemistry of haterumalide NA.",10.1021/ol0341804,2003-02-26,0.5924772704887655
Organic Letters,A Stereoselective Oxidative Dimerization En Route to (−)-Lomaiviticin A,"We describe a stereoselective synthesis of the dimeric diazofluorene 15, a potential precursor to the cytotoxic C 2 -symmetric bacterial metabolite (−)-lomaiviticin A ( 1 ). An efficient route was developed to convert the tetracyclic diol 5 to the diketone 4 (five steps, 30% overall). Oxidative dimerization of the enoxysilane 14 provided the C 2 -symmetric dimeric diazofluorene 15 in 56% yield and with 15:1:0 diastereoselectivity. Deprotection and 2D NMR analysis indicated that the major diastereomer possessed the (2 S,2′ S ) configuration found in 1 . This approach may ultimately be useful in the synthesis of 1 itself.",10.1021/acs.orglett.4c04098,2025-01-23,0.5924753885683193
Journal of Organic Chemistry,Synthesis of Cyclopenta[<i>c</i>]quinolines by Palladium-Catalyzed Cyclization of 3-Bromoindoles with Internal Alkynes via Spirocyclic Cyclopentadiene Intermediates,"A novel method for the construction of a cyclopenta[ c ]quinoline ring via cyclization of 3-bromoindoles with internal alkynes in the presence of palladium is described. The formation of the cyclopenta[ c ]quinoline ring is proposed from a double [1,5] carbon sigmatropic rearrangement of the spirocyclic cyclopentadiene intermediate, which is generated in situ from the cyclization of 3-bromoindoles with internal alkynes involving a sequential double alkyne insertion into the carbon–palladium bond and dearomatization of indole. The present studies have developed a novel ring-expansion reaction of the pyrrole ring to pyridine via one carbon insertion into the C2–C3 bond of indoles and provided a simple and distinct route for the construction of tricyclic fused-quinoline derivatives that are not easy to access with conventional methods.",10.1021/acs.joc.3c00716,2023-06-20,0.5924743670797107
Journal of Organic Chemistry,A Metal-Free Approach to the Synthesis of Indoline Derivatives by a Phenyliodine(III) Bis(trifluoroacetate)-Mediated Amidohydroxylation Reaction,"A novel approach to the synthesis of indoline derivatives is presented. The key cyclization step features the phenyliodine(III) bis(trifluoroacetate)- (PIFA-) mediated formation of a N-acylnitrenium ion and its succeeding intramolecular trapping by the olefin fragment. In addition, difunctionalization of the alkene moiety is achieved since the in situ generation of an additional hydroxy group at the terminal position of the original double bond accompanies the intramolecular C-N bond formation.",10.1021/jo061486q,2006-09-06,0.5924731806548024
Tetrahedron,"Convergent and enantioselective total synthesis of (−)-nalanthalide, a potential Kv1.3 blocking immunosuppressant",,10.1016/j.tetlet.2006.03.039,2006-03-30,0.5924680938215816
Synthesis,"Total Synthesis of Aculeatins A and B, and Formal Synthesis of Aculeatin D and 6-epi-Aculeatin D through an Asymmetric Aldol Reaction","A versatile and straightforward approach to the total synthesis of the dispirocyclic natural products aculeatins A, B, and D and 6- epi -aculeatin D was developed. The key steps involve a catalytic asymmetric aldol reaction using a titanium(IV) tetraisopropoxide/( S )-[1,1′-binaphthalene]-2,2′-diol system to form a C-2 hydroxy group, a hydroxy-directed­ reduction, and a Weinreb ketone synthesis.",10.1055/s-0034-1380228,2015-02-26,0.5924641316730157
Organic Letters,A Biosynthetic Proposal for Ring Formation in the Antitumor Agent Halichomycin. Asymmetric Synthesis of the AB-Carbon Backbone of Halichomycin,"[reaction: see text] A biosynthetic proposal for ring formation in the antitumor agent halichomycin is presented in which macrocyclization of the putative prehalichomycin intermediate 1 is the first step. Compound 2 then undergoes dehydration to the alpha-keto N-acylimine 3 followed by tandem nucleophilic addition of the C(16)-hydroxyl to form the hemimacrolactam. A stereospecific Michael ring closure and enol protonation complete C-ring assembly. So far, synthetic efforts toward 1 have resulted in 8.",10.1021/ol017266a,2002-02-22,0.592463431511243
Tetrahedron,An efficient and selective synthesis of nakienone A involving a novel protocol for α-alkenylation of ketones via palladium-catalyzed alkenyl-alkenyl coupling,,10.1016/s0040-4039(96)02409-4,1997-01-01,0.5924586573732089
Tetrahedron,"An efficient synthesis of enantiomerically pure (+)-(2S,5R)-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]cytosine [(+)-BCH-189] from d-galactose",,10.1016/s0040-4039(00)92319-0,1992-01-01,0.5924471605859429
Tetrahedron,Synthesis of unsymmetrical dibenzylketones: new procedures for the preparation and reduction of nitrostyrenes,,10.1016/s0040-4039(01)93006-0,1977-01-01,0.5924444369802527
Organic Letters,Asymmetric Synthesis of α-Methylphosphophenylalanine Derivatives Using Sulfinimine-Derived Enantiopure Aziridine-2-phosphonates,"[formula: see text] 2-Methylaziridine-2-phosphonates were prepared from enantiopure sulfinimines and were demonstrated to be versatile synthetic intermediates for the synthesis of novel alpha-disubstituted and alpha,beta-trisubstituted alpha-aminophosphonate derivatives. The first asymmetric synthesis of both enantiomers of alpha-methylphosphophenylalanine is described.",10.1021/ol990855k,1999-09-09,0.5924378794213087
Journal of Organic Chemistry,Synthesis of HKI 0231B,[reaction: see text] The total synthesis of HKI 0231B (1b) was completed in 12 linear steps and 15.6% overall yield. An unusual anionic cyclization provided access to intermediate 61 and the embedded benz[cd]indol-3-(1H)-one ring system 3. Directed ortho-lithiation in the presence of a ketone followed by formylation and finally acid-catalyzed methanolysis complete the synthesis. Studies directed toward the construction and reactivity of the lactam acetal functionality present in HKI 0231A (1a) are also reported.,10.1021/jo051762l,2005-10-25,0.5924193851274675
Synthesis,The Selective Synthesis of Unsymmetrical 1-Substituted 2(1<i>H</i>)-Pyrimidinones and -thiones,,10.1055/s-1983-30262,1983-01-01,0.5924182344425779
Organic Letters,Synthesis of the C7-26 Fragment of Amphidinolides G and H,"A new approach to the synthesis of the C7-26 fragment of amphidinolides G and H was developed. In the sequence, the C7-18 portion of this fragment was synthesized using an acetylide coupling protocol, while an Evans alkylation and Sharpless asymmetric dihydroxylation were employed as key steps in construction of the C19-26 subfragment. Finally, both of these units were joined by utilizing an aldol coupling reaction to produce the target C7-26 fragment in good yield.",10.1021/ol201547q,2011-07-11,0.5924153279059154
Synlett,"Synthesis of Functionalized Cyclopentane for Pactamycin, a Potent Antitumor Antibiotic","A tricyclic compound including a cyclopentane structure for pactamycin, an antitumor antibiotic, was constructed by Overman rearrangement and Pauson-Khand cyclization as key steps starting from diacetone-d-glucose.",10.1055/s-2004-837223,2005-01-01,0.5924119087635608
Tetrahedron,Regiospecific C-alkylation of uridine: a simple route to 6-alkyluridines,,10.1016/s0040-4039(01)86702-2,1979-01-01,0.5924113317342794
Tetrahedron,Synthesis and evaluation of a 5-membered isoiminosugar as glycosidase inhibitor,,10.1016/s0040-4039(98)01157-5,1998-08-01,0.5924043472299219
Organic Letters,A New Construction of 2-Alkoxypyrans by an Acylation−Reductive Cyclization Sequence,"A new convergent synthetic approach to a pyran motif common to many naturally occurring structures is described. In this approach, two fragments are joined by esterification, and a subsequent intramolecular reductive cyclization affords the 2-hydroxypyran.",10.1021/ol070573h,2007-04-12,0.5923997188920914
Journal of the American Chemical Society,Total Syntheses of (+)-Trienomycins A and F via a Unified Strategy,"The first total syntheses of (+)-trienomycins A and F, representative members of a new class of cytotoxic ansamycin antibiotics, have been achieved. Key features of the unified synthetic scheme included incorporation of the ( E, E, E )-triene unit with concomitant macrocyclization via a novel bis-Wittig olefination and the use of (2,2,2-trichloroethoxy)methyl protecting group for the secondary amide.",10.1021/ja961401a,1996-01-01,0.5923992614039307
Tetrahedron,"A concise and practical catalytic asymmetric synthesis of (−)-CP-99,994 and (−)-L-733,061",,10.1016/j.tetlet.2005.10.054,2005-11-09,0.5923992405776396
Synlett,A Cautionary Tale in Decanolide Synthesis,"An efficient convergent approach to the synthesis of the novel dioxolenone alcohol 3 is described and on thermolysis of 3 a macrodiolide, 12, was obtained via an intermediate β-acyl ketene. Macrodiolide 16 was obtained on thermolysis of the known dioxolenone alcohol 2 rather than the decanolide, diplodialide A.",10.1055/s-2008-1078031,2008-08-01,0.5923919327737063
Tetrahedron,An improved synthesis of N-aryl and N-heteroaryl substituted piperidones,,10.1016/j.tetlet.2007.02.053,2007-02-15,0.5923898794816954
Organic Letters,Synthesis of Benzothienobenzofurans via Annulation of Electrophilic Benzothiophenes with Phenols,"We have developed a metal-free, mild, and green synthetic route toward benzothieno[3,2- b ]benzofurans by the annulation of 3-nitrobenzothiophene with phenols. The reaction was found to be general with a range of substituted phenols. In addition, we could extend the methodology for the synthesis of pentacenes and could demonstrate the synthesis in gram-scale. Moreover, we extended the strategy for the synthesis of benzothieno[2,3- b ]benzofurans by starting from 2-nitrobenzothiophenes.",10.1021/acs.orglett.1c00219,2021-02-16,0.5923881161268894
Journal of Organic Chemistry,Total Synthesis of the Cardiotonic Steroid (+)-Cannogenol,"The total synthesis of (+)-cannogenol, an aglycon common to various biologically important cardiotonic glycosides, has been achieved. Synthesis of the versatile intermediate involves Mizoroki-Heck and intramolecular Diels-Alder reactions from the enantiomerically pure CD-ring segment, newly prepared in a multidecagram scale this time. Total synthesis by the site-selective transformations of the versatile intermediate demonstrated the applicability of our synthetic approach.",10.1021/acs.joc.0c02966,2021-02-04,0.5923872531635943
Tetrahedron,Intramolecular cycloadditions with isobenzofurans - X. 1 a novel synthesis of annulated hydroquinolines,,10.1016/0040-4039(95)01833-4,1995-11-01,0.5923847555033394
Synthesis,"Practical Synthesis of Variously Substituted 2,3,4-Benzothiadiazepine 2,2-Dioxides","Abstract The significant pharmacological activity of 2,3-benzodiazepine-4-ones led to an increased interest in this compound family. However, the literature of the closely related 2,3,4-benzothiadiazepine 2,2-dioxides is rather scarce. Earlier we elaborated a synthesis of 5-aryl congeners variously substituted at the aromatic ring. In the present study, a new synthetic route was investigated via highly versatile intermediates, to extend the reaction to a wider aromatic substitution pattern and to the preparation of 5-alkyl and 5-H derivatives. The essence of this approach is, starting from benzaldehyde acetals, acetophenone and benzophenone ketals, to synthesize ortho-formyl- and ortho-acyl-arylmethanesulfonyl chlorides, which are suitable precursors of the target compounds. The synthesis was implemented as follows: ortho-lithiation of the corresponding acetals and ketals and subsequent treatment with paraformaldehyde, or alternatively in two steps, with DMF or ethyl formate, followed by reduction with NaBH4, led to the corresponding hydroxymethyl derivatives. Reaction of these latter with methanesulfonyl chloride gave mesylates that were used to S-alkylate thiourea to afford S-alkylisothiouronium salts. The final steps of the synthesis were carried out in a telescoped reaction. Treatment of the S-alkylisothiouronium salts with N-chlorosuccinimide resulted in the corresponding arylmethanesulfonyl chlorides. Subsequent reaction with hydrazine hydrate followed by an acidic treatment gave 2,3,4-benzothiadiazepine 2,2-dioxides.",10.1055/a-1797-5298,2022-03-14,0.59238263386117
Organic Process Research & Development,"<i>N</i>,<i>N</i>-Diethyl-(<i>R</i>)-[3-(2-aminopropyl)-1<i>H</i>-indol-7-yloxy]acetamide:  Its Process Chemistry Ranging from Enantiocontrolled Construction of the Chiral Amine Side Chain to Regioselective Functionalization of the Aromatic Starting Materials","To access N, N -diethyl-( R )-[3-(2-aminopropyl)-1 H -indol-7-yloxy]acetamide ( 3 ), a key intermediate for AJ-9677 ( 2 ) acting as a potent and selective agonist for β 3 -adrenergic receptors, the ( R )-configured 2-aminopropyl side chain of 3 is elaborated in three distinct ways: (1) chiral pool synthesis featuring the C-3 acylation of 7-benzyloxy-1 H -indole ( 4a ) with N -(9-fluorenylmethoxycarbonyl)- d -alanyl chloride ( 6 ); (2) resolution of (±)-3-(2-aminopropyl)-7-benzyloxy-1 H -indole ( 8 ) via diastereomeric salt formation with O, O -di- p -toluoyl l -(2 R,3 R )-tartaric acid ( 21 ) to obtain ( R )- 8; and (3) crystallization-induced dynamic resolution (CIDR) by entrainment which transforms N, N -diethyl-(±)-[3-( N -phthaloyl-2-aminopropanoyl)-1 H -indol-7-yloxy]acetamide ( 26 ) entirely into ( R )- 26 . As regards 4a and 7-hydroxy-1 H -indole ( 4b ), the molecular scaffolds on which the above-mentioned chiral maneuvers are being executed, their synthetic approaches are explored threefold: (1) indole-ring construction on 3-benzyloxy-2-nitrotoluene [ 28; prepared from m -cresol ( 31 )] by the modified Leimgruber−Batcho method; (2) direct microbial hydroxylation of indole ( 34 ) at its C-7 position; and (3) indirect hydroxylation of indoline ( 35 ) at its C-7 position via a K 2 S 2 O 8 -mediated Baeyer−Villiger oxidation of the tricyclic product arising from the intramolecular Friedel−Crafts acylation of N -succinyl indoline ( 36 ).",10.1021/op060210h,2006-12-20,0.5923807648887913
Organic Letters,"Efficient and Selective Synthesis of 6,7-Dehydrostipiamide via Zr-Catalyzed Asymmetric Carboalumination and Pd-Catalyzed Cross-Coupling of Organozincs","[structure: see text] 6,7-Dehydrostipiamide has been synthesized in 23% yield in 15 steps in the longest linear sequence through the application of the Zr-catalyzed asymmetric carboalumination and the Pd-catalyzed organozinc cross-coupling in addition to the Brown crotylboration, the Corey-Peterson olefination, and the Corey-Fuchs reaction for carbon-carbon bond formation.",10.1021/ol048905v,2004-08-14,0.5923805965545255
Organic Letters,Practical Total Syntheses of Acromelic Acids A and B,"Practical total syntheses of acromelic acids A (1) and B (2), which have potent neuro-excitatory activity, were accomplished in 13 (36% total yield) and 17 steps (6.9% total yield), respectively, from 2,6-dichloropyridine (8). Regioselective transformation of symmetric 8 provided nitroalkenes 15 and 16. The pyrrolidine ring was efficiently constructed by Ni-catalyzed asymmetric conjugate addition followed by intramolecular reductive amination.",10.1021/ol500529w,2014-03-24,0.5923804735720639
Journal of Organic Chemistry,"Synthesis of 4,5-Dianilinophthalimide and Related Analogues for Potential Treatment of Alzheimer's Disease via Palladium-Catalyzed Amination","DAPH (4,5-dianilinophthalimide) has previously been shown to reverse the formation of neurotoxic fibrils associated with Alzheimer's disease. We have developed a synthetic route to DAPH and structurally related analogues that employs palladium-catalyzed amination as the key bond-forming step. The requisite substrates are easily obtained, and their coupling with substituted anilines proceeds in generally high yields. Thus, a variety of DAPH analogues can be quickly accessed in a modular fashion. In addition, the route described herein should also be amenable to the incorporation of other classes of nucleophiles into the molecular framework.",10.1021/jo051096o,2005-08-06,0.5923791558299013
Journal of the American Chemical Society,Processing 2-Methyl-<scp>l</scp>-Tryptophan through Tandem Transamination and Selective Oxygenation Initiates Indole Ring Expansion in the Biosynthesis of Thiostrepton,"Thiostrepton (TSR), an archetypal member of the family of ribosomally synthesized and post-translationally modified thiopeptide antibiotics, possesses a biologically important quinaldic acid (QA) moiety within the side-ring system of its characteristic thiopeptide framework. QA is derived from an independent l-Trp residue; however, its associated transformation process remains poorly understood. We here report that during the formation of QA, the key expansion of an indole to a quinoline relies on the activities of the pyridoxal-5'-phosphate-dependent protein TsrA and the flavoprotein TsrE. These proteins act in tandem to process the precursor 2-methyl- l-Trp through reversible transamination and selective oxygenation, thereby initiating a highly reactive rearrangement in which selective C2-N1 bond cleavage via hydrolysis for indole ring-opening is closely coupled with C2'-N1 bond formation via condensation for recyclization and ring expansion in the production of a quinoline ketone intermediate. This indole ring-expansion mechanism is unusual, and represents a new strategy found in nature for l-Trp-based functionalization.",10.1021/jacs.7b05337,2017-08-18,0.5923776359766175
Tetrahedron,Prostaglandins - a new total synthesis of (±)-11-deoxyprostaglandins,,10.1016/s0040-4039(01)84435-x,1972-02-01,0.5923737725172247
Tetrahedron,AN EXPEDITIOUS ROUTE TO 7α-SUBSTITUTED ESTRADIOL DERIVATIVES,,10.1016/s0040-4039(97)10180-0,1997-11-01,0.5923706192895337
Synlett,Progress toward the Total Synthesis of Guanacastepene A,"Guanacastepene A, the leading member of a structurally diverse family of diterpene natural products, was isolated from the extracts of an unidentified fungus. The discovery of its potent antibiotic activity as well as its previously unreported tricyclic architecture render guanacastepene A an attractive and formidable target for total synthesis. Specifically, guanacastepene A’s synthetic challenges include 2 ring-junction quaternary methyl groups and a novel 5-7-6 tricyclic carbon skeleton possessing a dense array of oxygen and unsaturated functionalities. In this account, we will discuss our motivation and efforts toward the total synthesis of guanacastepene A as well as highlight the contributions from the synthetic community toward this pursuit.",10.1055/s-2006-944213,2006-07-01,0.5923524697999146
Tetrahedron,Synthesis studies related to compactin and mevinolin: A new synthesis of the hexahydronaphthalene portion of compactin.,,10.1016/s0040-4039(00)81659-7,1983-01-01,0.5923505092082217
Synlett,Synthesis of New Pyrrolobenzazepinesvia Pictet-Spengler Cyclization,A new six-step divergent strategy was developed allowing access to pyrrolobenzazepine structures from pyrrole. This strategy was based on a regioselective Friedel-Crafts acylation followed by a Pictet-Spengler cyclization.,10.1055/s-2008-1078567,2008-07-02,0.5923479996196048
Organic Process Research & Development,"Development of a Synthesis of a 2,3-Disubstituted 4,7-Diazaindole Including Large-Scale Application of CH<sub>3</sub>Li/TiCl<sub>4</sub>-Mediated Methylation of an Enolizable Ketone","The chemical development of a 2,3-disubstituted 4,7-diazaindole is described. The requisite tertiary carbinol substrate was prepared employing in situ -generated CH 3 TiCl 3 as a chemoselective and preferred reagent compared to CH 3 MgX for methyl addition to an enolizable ketone. The 4,7-diazaindole ring system was efficiently assembled via an intramolecular Chichibabin transformation. The optimized processes were performed on pilot-plant scale to provide kilogram quantities of the target molecule.",10.1021/op5003769,2015-06-03,0.5923450493768282
Tetrahedron,"Reductive Heck coupling: an efficient approach toward the iboga alkaloids. Synthesis of ibogamine, epiibogamine and iboga analogs",,10.1016/j.tetlet.2012.01.097,2012-01-30,0.5923391800410673
Organic Letters,Asymmetric Synthesis of (+)-Geranyllinaloisocyanide: Assignment of Absolute Stereochemistry,"The first nonracemic synthesis of (+)-geranyllinaloisocyanide, starting with (-)-lactic acid methyl ester, has been accomplished by exploiting a [3.3] sigmatropic rearrangement of allyl cyanate. The synthesis enables assignment of the S configuration of the C(3) isocyano substituted, quaternary stereogenic center in natural geranyllinaloisocyanide.",10.1021/ol200308m,2011-04-14,0.592335496128138
Tetrahedron,"A practical synthesis of substituted benzo[c]cinnoline- N,N′-dioxides and N-oxides.",,10.1016/0040-4039(93)89037-q,1993-01-01,0.5923341787074771
Tetrahedron,Cycloaddition with stabilized imidates as potential azomethines ylides : A new route to 2-imidazoline and 4-yliden-s-imidazolinone,,10.1016/s0040-4039(00)60644-5,1993-09-01,0.5923223805174114
Organic Letters,Synthesis of the C8-Deoxyguanosine Adduct of the Food Mutagen IQ,"[structure: see text] The C8-2'-deoxyguanosine adduct of the food mutagen 2-amino-3-methylimadazo[4,5-f]-quinoline (IQ) has been synthesized. The key step is a palladium-catalyzed N-arylation of a suitably protected 8-bromo-2'-deoxyguanosine derivative.",10.1021/ol006968h,2001-01-20,0.5923174949925194
Journal of the American Chemical Society,Enantioselective Divergent Syntheses of (+)-Bulleyanaline and Related Isoquinoline Alkaloids from the Genus <i>Corydalis</i>,"possess potent and diverse biological activities. Herein, a concise, divergent, and enantioselective route to access these natural products is disclosed. Key transformations of our approach include a challenging Zn-ProPhenol-catalyzed asymmetric Mannich reaction to build a quaternary stereogenic center and a rapid cationic Au-catalyzed cycloisomerization to the common structural skeleton of these natural products. Subsequent late-stage oxidations and modifications allow efficient access to the targeted alkaloids. Overall, seven natural products have been successfully synthesized in 6 to 10 steps from readily available starting materials, including (+)-corynoline, (+)-anhydrocorynoline, (+)-12-hydroxycorynoline, (+)-12-hydroxycorynoloxine, (+)-corynoloxine, (+)-6-acetonylcorynoline, and (+)-bulleyanaline.",10.1021/jacs.9b08441,2019-09-16,0.5923118201645096
Tetrahedron,Tetrapyrroles. IV. A highly efficient synthesis of homochiral dihydropyrromethenones via Pdo mediated coupling of iodopyrroles and acetylenic amides,,10.1016/s0040-4039(00)60941-3,1992-10-01,0.5923103159385192
Organic Process Research & Development,One-Pot Process for the Amination of Oxazolidinyl-methyl Mesylate by Sodium Diformylamide,"An efficient one-pot process for the preparation of pure ( R )- N -[3-(4-iodophenyl)-2-oxo-5-oxazolidinyl]methylacetamide 1 from the mesylate 2b in 91% yield has been developed. The one-pot process makes use of commercially available sodium diformylamide 3 and avoids the use of highly hazardous reagents, simplifies workup procedures, and precludes detrimental impurity issues.",10.1021/op700062c,2007-05-31,0.5923063402270337
Organic Letters,Novel Synthesis of Heterocycles Having a Functionalized Carbon Center via Nickel-Mediated Carboxylation:  Total Synthesis of Erythrocarine,"Novel synthetic procedure of heterocycles was developed using nickel-mediated alkylative carboxylation, and the total synthesis of erythrocarine was achieved using this method and RCM of dienyne as the key steps. [reaction: see text]",10.1021/ol034670w,2003-05-31,0.5923028604117512
Tetrahedron,Synthesis of (S)-2-amino-8-oxodecanoic acid (Aoda) and apicidin A,,10.1016/s0040-4039(01)01331-4,2001-09-01,0.5922977286230137
Tetrahedron,Electroorganic synthesis of 6-aminonicotinic acid from 2-amino-5-chloropyridine,,10.1016/s0040-4039(03)00816-5,2003-05-01,0.5922977286230137
Tetrahedron,p-(3-Carboxy- and 3-carboxymethyl-1-adamantyl)calix[4]arenes: synthesis and arming with amino acid units,,10.1016/j.tetlet.2004.06.129,2004-07-22,0.5922977286230137
Synthesis,Synthesis of (<i>S</i>)-<i>N</i>-Benzyloxycarbonyl-4-amino-2-hydroxybutanoic Acid,,10.1055/s-1982-29691,1982-01-01,0.5922977286230137
Tetrahedron,Synthesis of 4′-amino-4′-deoxy analog of pantothenic acid,,10.1016/s0040-4039(01)95555-8,1979-01-01,0.5922977286230137
Tetrahedron,The synthesis of alanosine [L-2-amino-3-(N-nitrosohydroxylamino)propionic acid],,10.1016/s0040-4039(01)99793-x,1966-01-01,0.5922977286230137
Synthesis,Synthesis of Both Enantiomers of the Streptomyces Alkaloid 4-epi-SS20846A,"The enantiodivergent synthesis of the Streptomyces alkaloid 4- epi -SS20846A was based on a Takai olefination/Suzuki–Miyaura­ coupling sequence for the highly stereoselective introduction of the E , E -pentadienyl side chain on the piperidine skeleton. Optical separation of a key hydroxylated enamide ester, prepared by palladium-catalyzed methoxycarbonylation of a lactam-derived enol phosphate, was successfully achieved by both lipase-catalyzed kinetic resolution and semipreparative HPLC. This approach allowed us to obtain the enantiopure target alkaloid in 35–38% yield over six steps.",10.1055/s-0032-1317490,2012-10-24,0.5922941716709175
Tetrahedron,"Stereocontrolled total synthesis of (±)-3β-hydroxy-9β-pimara-7,15-diene, a putative biosynthetic intermediate of momilactones",,10.1016/j.tetlet.2011.04.044,2011-04-19,0.5922926096421496
Angewandte Chemie International Edition,Total Synthesis of (+)‐Madangamine D,"Madangamines are a group of bioactive marine sponge alkaloids, embodying an unprecedented diazapentacyclic skeletal type. The enantioselective total synthesis of madangamine D has been accomplished, and represents the first total synthesis of an alkaloid of the madangamine group. It involves the stereoselective construction of the diazatricyclic ABC core using a phenylglycinol-derived lactam as the starting enantiomeric scaffold and the subsequent assembly of the peripheral macrocyclic rings. The synthesis provides, for the first time, a pure sample of madangamine D and confirms the absolute configuration of this alkaloid family.",10.1002/anie.201402263,2014-05-02,0.5922924942366666
Journal of Organic Chemistry,"Ring-Enlargement of Dimethylaminopropenoyl Cyclopropanes: An Efficient Route to Substituted 2,3-Dihydrofurans","A convenient and efficient synthesis of substituted dihydrofurans is developed via ring-enlargement of 1-dimethylaminopropenoyl-1-carbamoyl/benzoyl cyclopropanes catalyzed by ammonium acetate in acetic acid with high regio- and stereoselectivity. Some of the newly synthesized substituted dihydrofurans are subjected to further synthetic transformation in the presence of NaOH (aq) in ethanol to afford the corresponding 5-aryl-2,3-dihydrofuro[3,2-c]pyridin-4(5H)-ones in high yields.",10.1021/jo801289p,2008-09-18,0.5922921471493588
Journal of Organic Chemistry,Enantioselective Total Syntheses of (−)-FR901483 and (+)-8-<i>epi</i>-FR901483,"The enantioselective total syntheses of the potent immunosuppressant FR901483 (1) and its 8-epimer (47) have been accomplished. Our approach features the use of building block 6 as the chiron, the application of the one-pot amide reductive bis-alkylation method to construct the chiral aza-quaternary center (dr = 9:1), regio- and diastereoselective intramolecular aldol reaction to build the bridged ring, and RCM to form the 3-pyrrolin-2-one ring.",10.1021/jo302362b,2012-12-05,0.5922884213787142
Tetrahedron,"An efficient synthesis of optically active (2R,3R)-2-methyl-3-[(1R)-1-methylprop-2-enyl]cyclopentanone, a useful chiral building block for synthesis of vitamin D and steroids",,10.1016/s0040-4039(03)00152-7,2003-03-01,0.5922850258156255
Organic Letters,"Asymmetric Total Synthesis of Novel Pentacyclic Indole Alkaloid, Kopsiyunnanine E, Isolated from <i>Kopsia arborea</i>","A new pentacyclic indole alkaloid, kopsiyunnanine E, was isolated from Yunnan Kopsia arborea, and its structure, which was inferred from spectroscopic data, was established by a 16-step asymmetric total synthesis that proved that the natural alkaloid was not enantiomerically pure.",10.1021/ol502265q,2014-09-24,0.5922830390823166
Tetrahedron,Selective synthesis of anomeric α-glycosyl acetamides via intramolecular Staudinger ligation of the α-azides,,10.1016/j.tetlet.2003.12.159,2004-01-27,0.5922811731765124
Journal of Organic Chemistry,"Synthesis of Novel Analogues of 1α,25-Dihydroxyvitamin D<sub>3</sub> with Side Chains at C-18","Novel analogues of the hormone 1alpha,25-(OH)(2)-D(3) with side chains attached to C-18 were synthesized by a versatile route in which key steps were the remote radical-induced functionalization of the 18-methyl by the C-8beta-hydroxyl group and the introduction of the side chains by Wittig reactions on a C-18-aldehyde. The triene system of the novel analogues was constructed by the convergent Lythgoe-Hoffmann la Roche approach, which involves reaction of a phosphine oxide (the ring A fragment) with a ketone (the upper fragment).",10.1021/jo0498664,2004-06-12,0.5922775907224084
Organic Letters,"An Expeditious Approach toward the Total Synthesis of CP-263,114","[reaction: see text] Assembly of the carbocyclic core of CP-263,114 has been accomplished efficiently and in high yield. Key steps include a phenolic oxidation/intramolecular Diels-Alder sequence, tandem radical cyclization, and the late-stage fragmentation of a densely functionalized isotwistane skeleton.",10.1021/ol015979n,2001-07-10,0.5922744929361233
Tetrahedron,Facile preparation of deoxybenzoins via a novel synthesis of enamines,,10.1016/s0040-4039(00)74286-9,1991-03-01,0.592272927286138
Organic Letters,Synthesis of the Tetracyclic Core of Daphnilactone B-Type and Yuzurimine-Type Alkaloids,"The core of daphnilactone B-type and yuzurimine-type alkaloids was synthesized in only 16 steps from a known β-allyl-γ-butyrolactone. The key sequence of Vilsmeier-Haack cyclization and intramolecular azomethine ylide cycloaddition allowed the construction of, in a single step, three of the five rings common to all alkaloids found in both of these classes with perfect chemocontrol.",10.1021/ol202629d,2011-10-28,0.5922697722845482
Angewandte Chemie International Edition,A Bio‐Inspired Total Synthesis of Tetrahydrofuran Lignans,"Lignan natural products comprise a broad spectrum of biologically active secondary metabolites. Their structural diversity belies a common biosynthesis, which involves regio- and chemoselective oxidative coupling of propenyl phenols. Attempts to replicate this oxidative coupling have revealed significant challenges for controlling selectivity, and these challenges have thus far prevented the development of a unified biomimetic route to compounds of the lignan family. A practical solution is presented that hinges on oxidative ring opening of a diarylcyclobutane to intercept a putative biosynthetic intermediate. The effectiveness of this approach is demonstrated by the first total synthesis of tanegool in 4 steps starting from ferulic acid, as well as a concise synthesis of the prototypical furanolignan pinoresinol.",10.1002/anie.201408641,2015-01-12,0.5922697206205858
European Journal of Organic Chemistry,Stereodivergent Total Syntheses of (+)‐Monomorine I and (+)‐Indolizidine 195B,"Abstract A simple and efficient stereoselective total syntheses of two natural products (+)‐monomorine I and (+)‐indolizidine 195B in high yields starting from a readily available alcohol is described. The key step in this synthetic route exploits the judicious use of solvent to enable a closed or open transition state in a nucleophilic addition of Grignard reagent to sulfinimine, giving selective access to two distinct diastereomers required for the formation of the two target natural products.",10.1002/ejoc.202100453,2021-07-21,0.5922691041005039
Synthesis,Synthetic Approaches to Rapamycin: Synthesis of a C10-C26 Fragment via a One-Pot Julia Olefination Reaction,"All articles of this category Key steps in a synthesis of the C10-C26 fragment of the immunosuppressant Rapamycin include (a) the use of a metallated benzothiazolyl sulfone in a one-pot Julia olefination to create the C21-C22 alkene stereoselectively and (b) a diastereoselective acid-catalysed cyclisation of a hydroxyl function onto a ketenedithioacetal (1,4-asymmetric induction) in order to create the oxane ring and fix the stereochemistry at C11. rapamycin - immunosuppressant - ketenedithioacetal - triene 1,4-asymmetric induction - Julia olefination",10.1055/s-1996-4184,1996-02-01,0.5922637200332558
Organic Process Research & Development,"Production Scale Synthesis of the Non-Nucleoside Reverse Transcriptase Inhibitor Atevirdine Mesylate (U-87,201E)","A practical synthesis of atevirdine mesylate, Pharmacia & Upjohn's first-generation non-nucleoside reverse transcriptase (RT) inhibitor for treatment of AIDS, is described. The route consists of three steps. In the first step, the starting material, 3-amino-2-chloropyridine, is N -ethylated by conversion into the acetimidate (1.25 equiv of trimethyl orthoacetate, 0.003 equiv of HOTs·H 2 O, neat; then distill off the MeOH to drive the amine/imidate equilibrium to imidate) followed by reduction with DIBAL (2.27 equiv, toluene, <−10 °C). In the second step, the N -ethyl derivative is heated in 5.13 equiv of piperazine at ∼170 °C in a closed system under moderate pressure (∼10 psig) to give 3-( N -ethylamino)-2-(1-piperazinyl)pyridine, which is purified by crystallization from water. An X-ray crystallographic study revealed that the crystal contains five molecules of water per molecule of 3-( N -ethylamino)-2-(1-piperazinyl)pyridine. The molecules pack in an interesting way, with two layers of piperazinylpyridine molecules sandwiched between layers of water molecules, as in the lipid bilayer structure of the biological cell membrane. The yield for the first two steps is 79.2% (overall, average of six plant runs). In the third step, the pentahydrate is coupled with 5-methoxyindole-2-carboxylic acid (MICA; 1.07 equiv of CDI, CH 2 Cl 2, 30 °C, 2−3 h; then add 1.06 equiv of 3-( N -ethylamino)-2-(1-piperazinyl)pyridine, CH 2 Cl 2, 30 °C) to give atevirdine free base, which is converted into the mesylate salt (1.01 equiv of MeSO 3 H, methanol, 25 °C) and crystallized. The yield of the third step is 83.3% (overall from MICA; average of eight plant runs). The bulk drug typically contains <0.1% total impurities (by HPLC). This process was used to produce multiton quantities of bulk drug used in phase II clinical trials.",10.1021/op9600318,1997-03-01,0.5922632234179287
Synthesis,"One-Step Synthesis of Ethyl 3-Cyano-4,6-diary, 1-2-hydroxybenzoates",,10.1055/s-1982-29918,1982-01-01,0.5922619870588439
Journal of the American Chemical Society,Asymmetric Total Synthesis of Taxol,"Taxol is one of the most famous natural diterpenoids and an important anticancer medicine. Taxol represents a formidable synthetic challenge and has prompted significant interest from the synthetic community. However, in all the previous syntheses of Taxol, there have been no reports of closing the desired eight-membered ring through C1–C2 bond formation. Furthermore, the existence of Taxol-resistant tumors and side effects of Taxol make the development of new approaches to synthesize Taxol and its derivatives highly desirable. Here, we report the asymmetric total synthesis of Taxol using a concise approach through 19 isolated intermediates. The synthetically challenging eight-membered ring was constructed efficiently by a diastereoselective intramolecular SmI 2 -mediated pinacol coupling reaction to form the C1–C2 bond. The unique biomimetic oxygen ene reaction and the newly developed facile tandem C2-benzoate formation and C13 side chain installation improved the efficiency of the synthesis. The mild oxygen ene reaction under light conditions would be an alternative reaction involved in Taxol biosynthesis. This new convergent approach will allow the diverse creation of Taxol derivatives to enable further biological research.",10.1021/jacs.1c09637,2021-10-12,0.5922606900541925
Organic Letters,Total Synthesis of Isofregenedadiol,"The first total synthesis of isofregenedadiol, a bicyclic diterpene isolated from H. Viscosum, is reported starting from a D-(-)-pantolactone chiral pool. A one-pot quadruple reaction sequence comprising an enyne ring-closing metathesis/cross-metathesis/Diels-Alder/aromatization for the construction of a target skeleton is the highlight of the present synthesis.",10.1021/ol201336x,2011-06-23,0.592247758395899
Tetrahedron,"A single-step one pot synthesis of O,O′-dialkyl N,N-dialkylphosphoramidates from dialkylphosphites",,10.1016/j.tetlet.2016.07.019,2016-07-07,0.5922471698362529
Tetrahedron,A single-step one pot synthesis of dialkyl fluorophosphates from dialkylphosphites,,10.1016/j.tetlet.2015.06.014,2015-06-13,0.5922471698362529
Synthesis,"An Improved Synthesis of Thiophene-2,3-dicarboxylic Acid by Sequential Carboxylation",,10.1055/s-1980-29015,1980-01-01,0.5922380928207626
Synlett,The Synthesis of<i>N</i>-(Pyridylamino)tetrahydroisoquinolines and Benzazepines via The Pictet-Spengler Cyclization,All articles of this category A series of N -(pyridylamino)-tetrahydroisoquinolines and -benzazepines have been prepared using the Pictet-Spengler cyclization of an unprotected arylhydrazine as the key step. Pictet-Spengler - tetrahydroisoquinolines - benzazepines - tetrazines - chloromethyl methyl ether,10.1055/s-2000-6462,2000-01-01,0.5922365014005194
Journal of Organic Chemistry,A Two-Directional Synthesis of (±)-Perhydrohistrionicotoxin,"An entirely two-directional synthesis of (+/-)-perhydrohistrionicotoxin is presented, utilizing a tandem oxime formation/Michael addition/[3 + 2] cycloaddition as the key step. This approach also constitutes formal syntheses of (+/-)-histrionicotoxin and (+/-)-histrionicotoxin 235A.",10.1021/jo035639a,2004-02-06,0.5922342369999776
Organic Letters,Cyanoamidine Cyclization Approach to Remdesivir’s Nucleobase,"We report an alternative approach to the unnatural nucleobase fragment seen in remdesivir (Veklury). Remdesivir displays broad-spectrum antiviral activity and is currently being evaluated in Phase III clinical trials to treat patients with COVID-19. Our route relies on the formation of a cyanoamidine intermediate, which undergoes Lewis acid-mediated cyclization to yield the desired nucleobase. The approach is strategically distinct from prior routes and could further enable the synthesis of remdesivir and other small-molecule therapeutics.",10.1021/acs.orglett.0c03052,2020-10-21,0.59223353393598
Synlett,Synthetic Approach to Tetrodotoxin,"A novel and stereoselective approach to tetrodotoxin is described. The tricyclic compound having several key functional groups on the cyclohexane ring was synthesized from p-anisaldehyde with control of the four chiral centers. Iodoaminocyclization, 1,3-dipolar cycloaddition, and Baeyer-Villiger oxidation are the key steps of our approach.",10.1055/s-2002-32984,2002-01-01,0.5922318271508311
Tetrahedron,Synthesis of threo-β-aminoalcohols from aminoaldehydes via chelation-controlled additions. Total synthesis of l-threo sphingosine and safingol,,10.1016/j.tetlet.2012.05.153,2012-06-08,0.5922164827421345
Journal of Organic Chemistry,Total Synthesis of Cryptoacetalide,"We are reporting the first total synthesis of the tetracyclic terpene natural product cryptoacetalide. Key steps of the synthesis are a microwave-mediated [2+2+2] cyclo-trimerization reaction to construct the central benzene ring, and a light-mediated radical cyclization to assemble the spiro-ketal moiety.",10.1021/jo100867v,2010-06-25,0.5922142976234283
Angewandte Chemie International Edition,Total Synthesis of Cyathin A<sub>3</sub> and Cyathin B<sub>2</sub>,A stereoselective synthesis of cyathin A(3) and cyathin B(2) has been achieved by a Prins-type reaction of a cycloalkenyl cyclopropanol. Particularly noteworthy is the use of a spirocyclobutanone moiety as a convenient scaffold for an efficient ring-closing metathesis to stereoselectively construct a suitably functionalized seven-membered ring (see scheme).,10.1002/anie.200901669,2009-06-18,0.592211261718008
Journal of Organic Chemistry,Formal Total Synthesis of Batrachotoxin Enabled by Radical and Weix Coupling Reactions,"Batrachotoxin ( 1 ), originally isolated from a Columbian poison-dart frog, is a steroidal alkaloid. Its 6/6/6/5-membered carbocycle (ABCD-ring) contains two double bonds, one nitrogen, and five oxygen functionalities. We developed a radical-based convergent strategy and realized the total synthesis of 1 in 28 steps. The AB-ring and D-ring fragments were efficiently synthesized and linked by exploiting a powerful Et 3 B/O 2 -mediated radical coupling reaction. Vinyl triflate and vinyl bromide were then utilized for a Pd/Ni-promoted Weix coupling reaction to cyclize the C-ring. A hydroxy group of the C-ring was stereoselectively installed by a decarboxylative hydroxylation reaction to prepare an advanced intermediate of our previous total synthesis of 1 .",10.1021/acs.joc.3c02290,2023-12-05,0.592203484316038
Tetrahedron,"Total synthesis of macrocyclic glycosides, clemochinenosides A and B, and berchemolide, by fluorous mixture synthesis",,10.1016/j.tetlet.2009.08.068,2009-08-27,0.5922024771679216
Synlett,Catalytic Epoxypolyene Cyclization via Radicals: Highly Diastereoselective Formal Synthesis of Puupehedione and 8-<i>epi</i>-Puupehedione,A catalytic and highly stereoselective synthesis of a common building block for the marine natural product puupehedione (1) and its biologically more active 8-epimer is described. Our approach features a copper-catalyzed allylic substitution reaction of epoxyfarnesyl acetate and a diastereoselective titanocene-catalyzed epoxypolyene cyclization via radicals. The formal syntheses of 1 and 2 are completed by highly diastereoselective ring closures to the required benzodihydropyran units.,10.1055/s-2006-933139,2006-03-14,0.5922020334523017
Organic Process Research & Development,"Stereoselective Synthesis of a<i>cis</i>-Cedrane-8,9-diol as a Key Intermediate for an Amber Odorant","The naturally occurring (−)-α-cedrene exhibits a weak woody and cedarlike odor. In contrast, cis -cedrene acetonide, which is a derivative of cedrene, is an extremely powerful semisynthetic aroma molecule. The current process starting from cedrene yields cis -cedrene acetonide in an overall yield of <20%. Herein, we report two synthetic pathways toward this valuable product starting either by isomerization of commercially available cedrene epoxide or by photo-oxidation of (−)-α-cedrene to an allylic intermediate. The key step of the synthesis is the epoxidation of the protected or even unprotected allyl alcohol followed by the reductive opening of the epoxide. This reaction sequence leads to the respective cis -diol with the correct stereochemistry. Subsequent acetalization gives cis -cedrene acetonide in up to 78% overall yield. We also report our attempt to prepare the cis -diol with inverted stereochemistry. In this context, we inverted the configuration of the allylic alcohol via a Mitsunobu reaction. However, only the acetyl-protected alcohol could be epoxidized, leading the undesired trans -product in >99% yield.",10.1021/acs.oprd.0c00423,2020-12-19,0.5922002562929451
Synthesis,Efficient Stereoselective Total Synthesis of (+)-Cryptofolione and the First Synthesis of (-)-Cryptocaryalactone¹,"The stereoselective syntheses of the naturally occurring α-pyrone derivatives (+)-cryptofolione and (-)-cryptocaryalactone were efficiently accomplished by using propane-1,3-diol as the starting material. Keck allylation, Mitsunobu center inversion, and olefin cross metathesis were used as the key steps. (-)-Cryptocarya­lactone was synthesized here for the first time.",10.1055/s-0030-1260246,2011-09-29,0.5921999481065905
Journal of Organic Chemistry,"Enantioselective Total Synthesis of (−)-Triptolide, (−)-Triptonide, (+)-Triptophenolide, and (+)-Triptoquinonide","The first enantioselective total synthesis of (-)-triptolide (1), (-)-triptonide (2), (+)-triptophenolide (3), and (+)-triptoquinonide (4) was completed. The key step involves lanthanide triflate-catalyzed oxidative radical cyclization of (+)-8-phenylmenthyl ester 30 mediated by Mn(OAc)3, providing intermediate 31 with good chemical yield (77%) and excellent diastereoselectivity (dr 38:1). (+)-Triptophenolide methyl ether (5) was then prepared in > 99% enantiomeric excess (> 99% ee), and readily converted to natural products 1-4. In addition, transition state models were proposed to explain the opposite chiral induction observed in the oxidative radical cyclization reactions of chiral beta-keto esters 17 (without an alpha-substituent) and 17a (with an alpha-chloro substituent).",10.1021/jo9919613,2000-03-04,0.5921982800079719
Organic Letters,Total Synthesis of (+)-Lysergic Acid,"A stereocontrolled total synthesis of (+)-lysergic acid (1) is achieved using three metal-catalyzed methodologies for the construction of three key rings. Highlights of the synthesis include Pd-catalyzed indole synthesis to form the B ring, a RCM reaction to form the D ring, and an intramolecular Heck reaction to form the C ring.",10.1021/ol2018467,2011-08-25,0.5921944673617693
Journal of Organic Chemistry,Cyclohexenone Annelation by Alkylidene C−H Insertion:  Synthesis of Oxo-<i>T</i>-cadinol,"A new procedure for cyclohexenone annelation has been developed. Thus, alkylation of 4-isopropylcyclohexanone with allyl bromide gives, over several steps, ketone 8 . Exposure to (trimethylsilyl)diazomethane and MeLi smoothly cyclized 8 to the cyclopentene 9 by insertion of the intermediate alkylidene carbene into the unactivated methylene CH. On debenzylation, ozonolysis, and subsequent aldol condensation, 9 is transformed into oxo- T -cadinol ( 1 ).",10.1021/jo951949k,1996-01-01,0.5921860539893242
Angewandte Chemie International Edition,Total Synthesis of Complex Peptidyl Nucleoside Antibiotics: Asymmetric De Novo Syntheses of Miharamycin B and Its Biosynthetic Precursor,"Miharamycins belong to a class of peptidyl nucleoside antibiotics with a unique nine-carbon pyranosyl amino acid core and a rare 2-aminopurine moiety. Herein, we report the de novo total synthesis of miharamycin B and its biosynthetic precursor from 3-bromofuran and Garner's aldehyde through a modified Achmatowicz reaction. Many challenges were resolved toward the de novo synthesis of miharamycin B, including the introduction of a dense array of functional groups, the stereoselective construction of consecutive stereocenters, dealing with the variability of the anomeric positions, and promoting site-selectivity in the cyclization to form the tetrahydrofuran ring. This de novo synthesis strategy enables efficient preparation of 3'-substituted saccharides, allowing the study of their structure-activity relationships and mode of action, and meets the growing demand for the development of novel antibiotics inspired by miharamycin natural products.",10.1002/anie.202204907,2022-05-24,0.5921860072695723
Journal of Organic Chemistry,Oxocarbenium Ion Cyclizations for C-Branched Cyclitols:  Synthesis of a Relay Intermediate for Fumagillin Analogues,"A highly stereoselective oxocarbenium ion-alkene cyclization for synthesis of C-branched cylitols is described. This methodology was applied to 10S, a potentially versatile intermediate for side-chain analogues of the antiangiogenic agent fumagillin. Compound 10S was subsequently converted to diene 5. Because racemic 5 has been converted to racemic fumagillin, this synthesis of 5 constitutes a formal synthesis of the natural product.",10.1021/jo050888f,2005-07-28,0.5921831847949678
Tetrahedron,A Stille biaryl-coupling approach to dityrosines. Formal total synthesis of Hazimycin,,10.1016/j.tetlet.2005.02.078,2005-03-08,0.5921820730849354
Tetrahedron,A convergent synthesis of poststatin: Application of the acyl cyanophosphorane coupling procedure in the formation of a peptidic α-keto amide,"A convergent synthesis of the pentapeptide poststatin has been developed. The key step involves oxidative cleavage of an acyl cyanophosphorane. The resulting α,β-diketo nitrile is then coupled to the free amine of a C-terminal-dipeptidyl component to generate the protected natural product. Deprotection by hydrogenolysis furnishes poststatin.",10.1016/s0040-4039(96)02488-4,1997-02-01,0.5921745455319819
Organic Process Research & Development,Technical-Scale Homologation of a Cholanic Acid Derivative through the Barton Ester. A Practical Approach to 25-Hydroxy Vitamin D<sub>3</sub> and Congeners,"A novel method was developed of the homologation of a cholanic acid derivative using the Barton ester, as a practical approach to 25-hydroxy vitamin D and congeners. The method involves transformation of a cholanic acid derivative into a nor-bromide by using 2-mercaptopyridine N -oxide sodium salt and bromotrichloromethane and then alkylation of the bromide with dimethylmalonate followed by demethoxycarbonylation by Krapcho procedure. The major byproducts of the synthesis were isolated, and their structures were identified by spectroscopic and chemical methods. Our method is designed especially for the large-scale manufacturing of vitamin D compounds because it involves an intermediate that can be easily purified and it avoids the use of toxic and explosive diazomethane that is employed in the classical synthesis of vitamins D from natural steroids.",10.1021/op980018i,1998-06-05,0.5921494773821729
Tetrahedron,"Vinylphosphonium salt mediated stereoselective synthesis of cyclobutene derivatives. A facile route to highly electron-deficient 1,3-dienes",,10.1016/s0040-4039(98)01303-3,1998-08-01,0.5921410652394878
European Journal of Organic Chemistry,"Synthesis of 9-Methylene Analogs of Retinol, Retinal, Retinonitrile and Retinoic Acid","Retinoids, 9-methylene analogs of retinol, retinal, retinonitrile and retinoic acid, were synthesised from a new synthon β-methylenealdehyde.",10.1002/1099-0690(200105)2001:9<1731::aid-ejoc1731>3.0.co;2-u,2001-05-01,0.5921392562508049
Journal of Organic Chemistry,Total Synthesis of (+)-Isoschizandrin Utilizing a Samarium(II) Iodide-Promoted 8-Endo Ketyl−Olefin Cyclization,"The 13-step synthesis of (+)-isoschizandrin reported herein features a samarium(II) iodide-promoted 8-endo ketyl-olefin coupling to assemble the eight-membered ring present in the target concomitantly with the required functionality and stereochemistry. In constructing (+)-isoschizandrin as a single atropisomer, the synthesis utilizes a kinetic resolution of a seven-membered lactone using a CBS-oxazaborolidine.",10.1021/jo0347361,2003-08-20,0.5921390769627826
Angewandte Chemie International Edition,Nitrogen Insertion into a Corrole Ring: Iridium Monoazaporphyrins,A new route to rare porphyrinoids: The non-innocence of the corrole ring allows the oxidative ring insertion of a nitrogen atom under mild conditions (see scheme; NBS=N-bromosuccinimide). The resulting meso-substituted azaporphyrins exhibit high-energy Soret absorption bands and red luminescence. This new synthetic route will allow for the development of novel azaporphyrin complexes with relevance to the study of biomimetic oxidations.,10.1002/anie.201102913,2011-08-30,0.5921364345675557
Tetrahedron,A stereodivergent route to epimeric 2-piperidinylglycines: application to the synthesis of carbocyclic β-lactam derivatives,,10.1016/j.tetlet.2007.06.148,2007-07-05,0.5921198874839207
European Journal of Organic Chemistry,"The Biosynthesis of 3‐(<i>trans</i>‐2‐Nitrocyclopropyl)alanine, a Constituent of the Signal Metabolite Hormaomycin","Abstract Feeding experiments with Streptomyces griseoflavus using deuterium‐labeled racemic 3,3‐[D 2 ]‐ ( 6b ), 4,4‐[D 2 ]‐ ( 6c ), 5,5‐[D 2 ]‐ ( 6d ), and 6,6‐[D 2 ]‐lysine ( 6e ), and 3‐amino‐5‐(2‐amino‐1,1‐dideuterioethyl)‐4,5‐dihydrofuran‐2‐one dihydrochloride ( 34· 2HCl) were carried out in order to obtain detailed information about the hitherto unknown biosynthetic pathway from lysine to the unusual amino acid 3‐( trans ‐2′‐nitrocyclopropyl)alanine [(3‐Ncp)Ala] ( 2 ), which is a building block of hormaomycin 1a . The corresponding lysine dihydrochlorides were prepared in 33, 24, 19, and 30% overall yield, respectively, along a new efficient general synthetic route applying an alkylation of the lithium enolate of O′Donnel’s glycine equivalent 7 as a key step. In the attempted preparation of 5,5‐[D 2 ]‐4‐hydroxylysine ( 29 ), the respective γ‐lactone ( 34· 2 HCl) was obtained in five steps with 10% overall yield. The distribution of isotope labels in hormaomycins 1b − d led to the formulation of a reasonable cyclization mechanism of 2‐amino‐4‐hydroxy‐6‐(hydroxyimino)hexanoic acid, an ψ‐oxime analogue of 4‐hydroxylysine. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2005)",10.1002/ejoc.200400493,2004-12-20,0.5921166566266555
Tetrahedron,Harvesting short-lived hypoiodous acid for efficient diastereoselective iodohydroxylation in Crixivan® synthesis,,10.1016/s0040-4039(01)01863-9,2001-12-01,0.5921154014764453
Synlett,Practical Synthesis of 7-Azaserotonin and 7-Azamelatonin,"Abstract A practical method for synthesizing 7-azaserotonin and 7-azamelatonin was developed by using 3-bromo-5-methoxy-1-tosyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridin-2-ol as a starting material. This compound is a useful reactant for the formal C3-electrophilic reaction. The lactone derivative obtained by the reaction with Meldrum’s acid was used as a key intermediate, in which the C2 unit was introduced into the 7-azaindole skeleton.",10.1055/s-0041-1738758,2022-10-18,0.5921123437898458
Journal of Organic Chemistry,"Studies on Intramolecular Diels−Alder Reactions of Furo[3,4-<i>c</i>]pyridines in the Synthesis of Conformationally Restricted Analogues of Nicotine and Anabasine","En route to conformationally restricted analogues of nicotine and anabasine, a novel synthetic route to bridged anabasines is described that hinges on a domino intramolecular [4 + 2]-cycloaddition/ring opening-elimination sequence of 3-amino-substituted furo[3,4-c]pyridines. Extension of this route to bridged nicotines, however, proved abortive, even when the dienophile tether is activated by a p-tolylsulfonyl group or when the diene moiety is activated by an electron-releasing methoxy substituent. A detailed density functional theoretical study (B3LYP/6-31+G) was undertaken to provide insight into the factors that facilitate an intramolecular Diels-Alder reaction in the former case.",10.1021/jo026555p,2003-04-26,0.592110547399303
Journal of Organic Chemistry,Synthesis of Constrained Raloxifene Analogues by Complementary Use of Friedel−Crafts and Directed Remote Metalation Reactions,"New constrained heterocyclic analogues, 2a,b and 3, of Raloxifene (1) have been prepared by complementary Directed remote Metalation (DreM)/Friedel-Crafts cyclization approaches. Utilization of a benzylidene-thiolactone rearrangement was successfully implemented to construct benzothiophenes 13a-c in good yields. Selective deprotection of 13a and 13b induced by complexation followed by triflation gave 18 and 23, thereby allowing efficient Suzuki-Miyaura cross coupling with borolane 16 to give biaryls 19 and 24. Treatment of 19 with BCl(3) induced an intramolecular para Fridel-Crafts cyclization and concomitant double deprotection to furnish analogue 2a, a new 5,6,6,6-(C(4)S-C(6)-C(6)-C(6)) sulfur-containing heterocycle. Exposure of 25 with excess LDA induced a DreM cyclization delivering the ortho-substituted 5,6,6,6-(C(4)S-C(6)-C(6)-C(6)) heterocylic analogue 26 in 70% yield. Similar treatment of 13c and 27 afforded 30, representing the novel 5,5,6,6-(C(4)S-C(5)-C(6)-C(6)) ring system, which was subjected to Suzuki-Miyaura cross coupling with 16 to give the biaryl 31 in 93% yield; deprotection furnished the final constrained analogue 3.",10.1021/jo034325k,2003-06-28,0.59210882559529
Journal of Organic Chemistry,"An Efficient Synthesis of 4-(Phenylsulfonyl)-4<i>H</i>-furo[3,4-<i>b</i>]indoles","The fused heterocycle 4-(phenylsulfonyl)-4H-furo[3,4-b]indole, which is an indole-2,3-quinodimethane synthetic analogue, is prepared in five steps from indole in 46% yield. A similar sequence is used to synthesize C-3 derivatives (3-methyl, 3-phenyl, and 3-heptyl). Thus, indole-3-carbaldehyde (1) is protected as the N-phenylsulfonyl derivative 2 and converted to the ethylene acetal 6. Lithiation at C-2 followed by treatment with an aldehyde affords the expected hydroxy acetals 7 and 8. Exposure to acid effects cyclization to the furoindoles 5 and 9. Furthermore, C-1 lithiation of furo[3,4-b]indole 9c followed by treatment with methyl iodide affords disubstituted furo[3,4-b]indole 10.",10.1021/jo010938q,2002-01-15,0.5921002745290767
European Journal of Organic Chemistry,"An Optically Active 4‐Aryl‐3,4‐dihydroisocoumarin‐3‐carboxylate","Abstract A four step sequence for the preparation of optically active ( R , R )‐ethyl 4‐phenyl‐3,4‐dihydroisocoumarin‐3‐carboxylate is reported. In the first step the first stereocenter was installed by palladium catalyzed asymmetric conjugate addition of PhB(OH) 2 to indenone (88 % ee ). After deprotonation, the ester moiety was introduced with Mander's reagent. The α‐hydroxylation of the resulting β‐oxoester was then achieved with cerium‐catalysis under an air atmosphere. Key transformation was the cyanide‐catalyzed ring transformation of α‐hydroxy‐β‐oxoester furnishing the δ‐lactone moiety of the target compound, which was formed as a mixture of separable cis‐ and trans‐ diastereoisomers, both with 88 % ee . The cis‐ isomer could be epimerized to the trans ‐compound. The relative trans and the absolute ( R , R )‐configuration of the target compound was established by X‐ray single crystal structure analysis.",10.1002/ejoc.202400769,2024-08-13,0.5920984177396581
Synthesis,Chemoenzymatic Synthesis of All Four Cytoxazone Stereoisomers,"Racemic cytoxazone (±-5) was synthesized starting from easily available glycidic ester (±)-1 by nucleophilic epoxide ring opening, followed by 2-oxazolidinone ring construction and calcium chloride/sodium borohydride reduction of the intermediary ester (±)-4. Kinetic resolution of (±)-5 performed by acetylation with vinyl acetate catalyzed by Penicillium camemberti lipase (PcamL) afforded, on hydrolysis of acetate (-)-6, cytoxazone (-)-5 in 33% overall yield and 88.2% enantiomeric excess (ee), and its enantiomer (+)-5 (38% yield, 89.3% ee). Base-catalyzed epimerization of intermediary (±)-4 to (±)-7, and reduction and kinetic resolution with Candida antarctica lipase (CAL) led to epi-cytoxazones (-)-8 and (+)-8.",10.1055/s-2001-17711,2001-01-01,0.5920941674117344
Tetrahedron,Regiospecific synthesis of 1-acetamide-5-methoxy-2-oxindoles in two steps: (Ugi-SN2)/xanthate mediated free radical cyclization,,10.1016/j.tetlet.2014.10.026,2014-10-13,0.5920829043586131
Organic Letters,Enantiospecific Synthesis of Pseudoacarviosin as a Potential Antidiabetic Agent,"A pseudo-1,4'- N-linked disaccharide, pseudoacarviosin 5, was constructed via a key palladium-catalyzed coupling reaction of pseudoglycosyl chloride 8 (prepared from d-glucose via a novel direct intramolecular aldol addition in 12 steps) and pseudo-4-amino-4,6-dideoxy-alpha- d-glucose 9 (prepared from l-arabinose via an unusual trans-fused isoxazolidine-selective intramolecular nitrone-alkene cycloaddition in 11 steps). Pseudoacarviosin 5 has been shown to be a potent inhibitor of alpha-glucosidases, particularly the intestinal mucosal enzymes sucrase and glucoamylase of relevance to blood glucose control.",10.1021/ol8010503,2008-06-17,0.5920773691095729
Tetrahedron,A simple five-step synthesis of a pentadecaalkylcorrin derivative from commercial cyanocobalamin,,10.1016/s0040-4039(01)95444-9,1979-01-01,0.5920715655010411
Synthesis,"Stereospecific Total Synthesis of (+)-Davana Acid, (+)-Nordavanone and (+)-Davanone","A short, total synthesis of (+)-davana acid, (+)-nordavanone and (+)-davanone, which are principle components of davana oil, is described. The notable features are the use of the Evans syn aldol reaction and cyclic ether formation by an intramolecular SN2 displacement reaction as key steps.",10.1055/s-0029-1218603,2009-12-11,0.5920678164592464
Tetrahedron,A new pyridine synthesis from azoenamines,,10.1016/j.tetlet.2010.09.098,2010-09-28,0.5920662410145242
Journal of Organic Chemistry,Stereoselective Synthesis and Absolute Configuration of the C1′−C25′ Fragment of Symbiodinolide,"Stereoselective synthesis of the C1'-C25' fragment of symbiodinolide, which was obtained as a degraded product from symbiodinolide by alkaline hydrolysis, has been accomplished. The synthetic route features Kotsuki coupling and Julia-Kocienski olefination in the introduction of the side chains. This enantio- and stereoselective synthesis has established the absolute configuration of the C1'-C25' fragment.",10.1021/jo901162v,2009-08-05,0.5920651090469448
Journal of Organic Chemistry,"The tetramerization of 2,4-dimethoxycinnamates. A novel route to calixarenes","Treatment of (E)-2,4-dimethoxycinnamic acid methyl ester with BF3.Et2O in CHCl3 at room temperature afforded in 75% yield two stereoisomeric C-alkylcalix[4]resorcinarenes, which were shown to be in the 1,2-alternate and flattened-cone configurations.",10.1021/jo00038a001,1992-06-01,0.5920650031559599
Journal of Organic Chemistry,"6,6‘-Dibromo-4,4‘-di(hexoxymethyl)-2,2‘- bipyridine:  A New Solubilizing Building Block for Macromolecular and Supramolecular Applications","Although brominated bipyridines and terpyridines are highly desirable synthetic building blocks for both ligand design and macro- or supramolecular applications, few such synthetic precursors have been reported that include much-needed solubilizing groups. Reported here is an inexpensive route to 2,6-dibromo-4-(hexoxymethyl)pyridine from citrazinic acid with an overall yield of 44% and its efficient conversion (60%) to 6,6'-dibromo-4,4'-di(hexoxymethyl)-2,2'-bipyridine via oxidative coupling.",10.1021/jo060557i,2006-05-13,0.5920646729343065
Synthesis,"An Improved Synthesis of Symmetrical N,N′-Alkylidene-bis-amides",,10.1055/s-1972-21820,1972-01-01,0.5920633932270569
Synlett,Synthesis of Novel Azole Antifungals by a Modified Sharpless Asymmetric Dihydroxylation,"All articles of this category An improved synthesis of the azole antifungal building block (Figure), exemplified by a formal synthesis of Sch 45450, is described. Asymmetric induction was achieved by a modified Sharpless dihydroxylation (AD) reaction which generated products with excellent enantiomeric excess.",10.1055/s-1994-22820,1994-01-01,0.5920632847230795
Tetrahedron,"Synthetic approaches to eudistomins. Part 1. Synthesis of 1-amino-3-thiaindolo [2,3- ] quinolizidine",,10.1016/s0040-4039(00)85405-2,1986-01-01,0.5920603182066336
Synthesis,Unified Approach to ent-Eudesmane-Type Terpenoid Synthesis: Total Synthesis of Sinupol and Eutyscoparin A,"Abstract ent-Eudesmane-type terpenoids constitute a large class of natural products derived from plants, animals, and bacteria. We describe a synthetic approach to two ent-eudesmane-type terpenoids, sinupol and eutyscoparin A, that relies on a key π-facial- and endo/exo-selective intramolecular Diels–Alder reaction to set the C-5–C-10 stereotriads. Further key transformations of trans-fused decalin include conversion to methyl ketone via a versatile thioester intermediate and appropriate functionalization toward target compounds.",10.1055/a-1643-5729,2021-09-13,0.5920578231299038
Tetrahedron,Asymmetric synthesis of palitantin from the (5R)-tert-butyldimethylsiloxy-2-cyclohexenone,,10.1016/s0040-4039(99)01549-x,1999-10-01,0.5920561456713181
Journal of Organic Chemistry,An Alternative Approach to Synthesize Sildenafil via Improved Copper-Catalyzed Cyclization,"A facile synthetic pathway for sildenafil has been developed. This approach is characterized by a ligand-free Ullmann-type copper-catalyzed coupling reaction to construct sildenafil and its derivative, pyrrazolo[4,3- d ]pyrimidin-7-one ring, with yields of 79% and 82%, respectively, in a convergent fashion by connecting key building blocks halo-pyrazole moiety 16c with 2-ethoxybenzamidine and 2-ethoxy-5-[(4-methylpiperazin-1-yl)sulfonyl]benzamidine in a one-pot reaction. Thus, this approach circumvents the need to use nitric/sulfuric acid for nitration, a costly Pd-catalyst for reduction, and coupling agents encountered in the reported processes.",10.1021/acs.joc.4c00393,2024-05-06,0.592055767581577
Organic Process Research & Development,Asymmetric Synthesis of (<i>S</i>)-3-Amino-4-methoxy-butan-1-ol by Way of Reductive Amination,"A new synthesis of ( S )-3-amino-4-methoxy-butan-1-ol is reported. The synthesis is based on the preparation of the primary, nonprotected enamine of the commercially available β-keto ester methyl 4-methoxy-3-oxo-butanoate and asymmetric catalytic enamine hydrogenation using a Ru-MeOBIPHEP catalyst. Alternatively, the process is performed by asymmetric catalytic reductive amination of the β-keto ester with ammonium acetate and hydrogen using a similar Ru catalyst. Both process versions provided initial ee values of 97−98% which were upgraded to ≥99% by product crystallization. Ester to alcohol conversion was best accomplished by LiBH 4 reduction after transitory Boc protection of the amino group.",10.1021/op1002775,2011-01-18,0.5920527071823697
Organic Process Research & Development,Development of Dual Practical Manufacturing Routes to Cognate Pyrrolobenzodiazepine-Based Linker-Drugs,"The synthetic strategies for two distinct but related linker-toxins 1 and 2 were reconfigured in order to devise an efficient and unified supply chain for both compounds. This involved establishing novel chemical routes to crystalline, monomeric building blocks that could be combined in a unique way for each molecular target. This streamlined approach avoided challenging desymmetrization efforts en route to each target molecule as well as a drastically reduced need for multiple chromatographic purifications throughout the syntheses. In the final instance, the shared-building-block concept enabled access to advanced intermediates from which the optimized endgames were implemented, ultimately resulting in robust synthetic processes to both 1 and 2 .",10.1021/acs.oprd.2c00129,2022-08-08,0.5920518252440664
Synthesis,"A Facile Synthesis of Ethyl 2-Acetamido-4-methylenehex-5-enoate, a Versatile Diels-Alder Synthon for the Parallel Synthesis of Novel α-Amino Acid Derivatives",An efficient synthesis of a diene-containing α-amino acid via the use of Denmark’s coupling reaction and its application to the synthesis of novel α-amino acid via the Diels-Alder reaction are described.,10.1055/s-2006-958929,2006-12-20,0.5920516751062302
Tetrahedron,Silver-catalyzed one-step synthesis of multiply substituted quinolines,,10.1016/j.tetlet.2015.12.028,2015-12-12,0.5920496614917262
Journal of Organic Chemistry,"Synthesis of 7-Oxo-dihydrospiro[indazole-5,4′-piperidine] Acetyl-CoA Carboxylase Inhibitors","Synthesis of oxo-dihydrospiroindazole-based acetyl-CoA carboxylase (ACC) inhibitors is reported. The dihydrospiroindazoles were assembled in a regioselective manner in six steps from substituted hydrazines and protected 4-formylpiperidine. Enhanced regioselectivity in the condensation between a keto enamine and substituted hydrazines was observed when using toluene as the solvent, leading to selective formation of 1-substituted spiroindazoles. The 2-substituted spiroindazoles were formed selectively from alkyl hydrazones by ring closure with Vilsmeier reagent. The key step in the elaboration to the final products is the conversion of an intermediate olefin to the desired ketone through elimination of HBr from an O-methyl bromohydrin. This methodology enabled the synthesis of each desired regioisomer on 50-75 g scale with minimal purification. Acylation of the resultant spirocyclic amines provided potent ACC inhibitors.",10.1021/jo202377g,2012-01-12,0.5920475142190001
Organic Letters,"Synthesis of Ring-Locked Tetracyclic Dithienocyclopentapyrans and Dibenzocyclopentapyran via 1,5-Hydride Shift and Copper-Catalyzed C–O Bond Formation for Nonfullerene Acceptors","We discovered a unique synthetic route to construct 2H-pyran-containing tetracyclic dithienocyclopentapyran (DTCP) and dibenzocyclopentapyran (DBCP) architectures. The synthesis involves an acid-induced dehydration cyclization followed by a [1,5] hydride-shift isomerization to form a cyclopentanone moiety which was converted to the pyran-embedded tetracyclic products by a CuI-catalyzed intramolecular C-O bond formation in good yield. DTCP was used as a building block to prepare an acceptor-donor-acceptor (A-D-A) type n-type material DTCP-BC leading to a solar cell efficiency of 9.32%.",10.1021/acs.orglett.1c00110,2021-02-23,0.5920439622522595
Tetrahedron,"Deprotection of carbonyl croups by anodic oxidation of dithioacetals : A key step in the synthesis of α-diones, α-ketols and chiral synthons.",,10.1016/0040-4039(90)80135-9,1990-01-01,0.5920419750335104
Organic Letters,"Enantiospecific Synthesis of (+)-<i>N</i><sub>a</sub>-Methylpericyclivine and (−)-<i>N</i><sub>a</sub>-Methylakuammidine as Well as the Ring-A Oxygenated Natural Products, (+)-10-Methoxy <i>N</i><sub>a</sub>-Methylpericyclivine and 10-Hydroxy <i>N</i><sub>a</sub>-Methylpericyclivine","[reaction: see text] The first enantiospecific, regiospecific total synthesis of the enantiomers of N(a)-methylpericyclivine and N(a)-methylakuammidine as well as the ring-A oxygenated natural products (+)-10-methoxy N(a)-methylpericyclivine and 10-hydroxy N(a)-methylpericyclivine was achieved. The lactones (see 19, 22, and 25) are key to the formation of the beta-axial methyl ester moiety.",10.1021/ol0526266,2006-02-14,0.5920345452050162
Tetrahedron,Exploratory studies toward a synthesis of flavaglines. A novel access to a highly substituted cyclopentenone intermediate,,10.1016/j.tetlet.2014.12.093,2014-12-23,0.5920319088012245
Organic Letters,"Synthesis of 9,11-Secosteroids Pinnisterol E, Glaciasterol B, and 6-Keto-aplidiasterol B","A 10-step gram-scale synthesis of 9,11-secosteroid pinnisterol E from the inexpensive ergosterol is reported. This synthesis features a series of highly selective redox transformations such as regioselective olefin hydrogenation (PtO 2 ), acid-sensitive endoperoxide reduction (Al–Ni alloy, Zn), and regio- and diastereoselective dienone oxidation. The robustness of this strategy is clearly demonstrated through the formal synthesis of 11(9 → 7) abeo -steroid pleurocin B and the divergent synthesis of 9,11-secosteroids glaciasterol B and 6-keto-aplidiasterol B from the inexpensive cholesterol.",10.1021/acs.orglett.2c00281,2022-02-23,0.5920319014266301
Angewandte Chemie International Edition,"Total Synthesis of Everninomicin 13,384-1—Part 3: Synthesis of the DE Fragment and Completion of the Total Synthesis",,10.1002/(sici)1521-3773(19991115)38:22<3345::aid-anie3345>3.0.co;2-9,1999-11-15,0.5920313984725788
Synlett,An Expeditious Route Towards Pyranopyran Sugar Amino Acids,"The synthesis of two diastereoisomeric pyranopyran sugar amino acids, starting from (+)-d-3,4,6-tri-O-benzylglucal, is described. The key reaction sequence towards the bicyclic structure entails Petasis olefination followed by ring closing metathesis.",10.1055/s-2004-820021,2004-01-01,0.5920311775405975
Journal of Organic Chemistry,First Total Synthesis and Assignment of the Stereochemistry of Crispatenine,"The first racemic and enantioselective synthesis of crispatenine 1 has been achieved, which involved a few steps, enabling the assignment of the absolute and relative configurations.",10.1021/jo070045j,2007-04-19,0.5920305719738906
Organic Letters,Hydroxyl-Substituted Ladder Polyethers via Selective Tandem Epoxidation/Cyclization Sequence,A new and highly selective method for the synthesis of hydroxyl-substituted tetrahydropyrans is described. This method utilizes titanium(IV) isopropoxide and diethyl tartrate to perform a diastereoselective epoxidation followed by in situ epoxide activation and highly selective endo-cyclization to form the desired tetrahydropyran ring. The HIJ ring fragment of the marine ladder polyether yessotoxin was synthesized using this two-stage tactic that proceeds with high efficiency and excellent regioselectivity.,10.1021/ol503400j,2015-02-03,0.5920257122742688
Tetrahedron,"Mono-N-alkylation of anthranilamides via quinazolinones. An efficient synthesis of G5598, a benzodiazepine dione gpIIbIIIa antagonist",,10.1016/s0040-4039(00)76773-6,1994-04-01,0.5920216756361358
Synthesis,"Probes for Narcotic Receptor Mediated Phenomena; 29: Synthesis of<i>rac</i>-(4<i>R</i>,6a<i>R</i>,11b<i>R</i>)-3-Methyl-2,3,4,5,6,6a-hexahydro-1<i>H</i>-4,11b-methanobenzofuro[3,2-<i>d</i>]azocin-10-ol, the<i>para</i>-a Oxide-Bridged Phenylmorphan Isomer, and a New Route to<i>rac</i>-(4<i>R</i>,6a<i>R</i>,11b<i>R</i>)-3-Methyl- 2,3,4,5,6,6a-hexahydro-1<i>H</i>-4,11b-methanobenzofuro[3,2-<i>d</i>]azocin-8-ol, the<i>ortho</i>-a Oxide-Bridged Phenylmorphan Isomer","A six-step synthesis of the para-a oxide-bridged phenylmorphan isomer rac-(4R,6aR,11bR)-3-methyl-2,3,4,5,6,6a-hexahydro-1H-4,11b-methanobenzofuro[3,2-d]azocin-10-ol (4), was achieved using Okahara’s reagent, 3-chloro-2-methoxymethoxy­propene, to prepare the key intermediate 8. Bromination was directed at the desired carbon atom via the correctly positioned ketone moiety in 8. O-Demethylation followed by subsequent displacement of the bromine by the phenolic ion in situ gave ketone 9 that, after reduction to the alcohol and conversion to the bis-mesylate, could be reduced to obtain the desired product. The structure of 4 was unequivocally determined by an X-ray spectroscopic study. A similar sequence of reactions provided a novel, much shorter synthetic route to the known ortho-a oxide-bridged phenylmorphan isomer.",10.1055/s-2002-35237,2002-01-01,0.5920189866389858
Organic Letters,Total Synthesis of Hypermodified Epothilone Analogs with Potent in Vitro Antitumor Activity,"The convergent total synthesis of hypermodified epothilone analogs 1 and 2 has been achieved with the stereoselective cyclopropanation of allylic alcohol 17 and ring-closing olefin metathesis with diene 22 as the key steps. In spite of significant structural differences between these analogs and the natural epothilone scaffold, 1 and 2 are potent inducers of tubulin polymerization and inhibit the growth of human cancer cells in vitro with sub-nM IC50 values.",10.1021/ol800089x,2008-02-28,0.592014968947314
Organic Letters,"Formal Total Synthesis of Fostriecin via 1,4-Asymmetric Induction Using Cobalt-Alkyne Complex","The synthesis of a protected dephosphofostriecin, and thereby a formal synthesis of fostriecin, has been accomplished. Two of the four chiral centers are controlled by an external chiral auxiliary and the other two are synthesized stereoselectively, one by a novel 1,4-asymmetric induction using cobalt-alkyne complex, and the other by 1,3-asymmetric induction.",10.1021/ol800195g,2008-03-04,0.5920140186405782
Synthesis,"Synthesis and Reactivity of 1-(8-Amino-1-naphthyl)-1<i>H</i>-1,2,3-triazoles","All articles of this category An efficient synthesis of new peri -substituted naphthalenes 3 and their intramolecular cyclization, Schiff base formation, N -methylation, and acetylation are reported.",10.1055/s-1987-28115,1987-01-01,0.5920108595414454
Synthesis,Synthesis of Racemic Ethanolamine Plasmalogen,All articles of this category Racemic C 12 -ethanolamine plasmalogen 5b was prepared in high yield. The amino group was generated by selective reaction of azide 4b with polymeric triphenylphosphine followed by mild hydrolysis of the intermediate phosphine imine. A novel universal phosphorylation reagent 2-azidoethyl dichlorophosphate (7) was used. plasmalogen - synthesis - ethanolamine-phospholipids - 2-azidoethyl dichlorophosphate - polymeric triphenylphosphine,10.1055/s-1996-4390,1996-11-01,0.5920086700394583
Synlett,"A Tandem Route to the Synthesis of Carbazolo[1,2-b]carbazoles","A simple and facile synthesis of carbazolo[1,2-b]carbazole derivatives via Michael addition of 2-methylindole, condensation of methyl group with the carbonyl, dehydration followed by aromatization by heating in hydrothermal oven is reported.",10.1055/s-0030-1289514,2011-10-01,0.5920051625285556
Tetrahedron,Trifluoromethyl group in the synthesis of heterocyclic compounds: New and efficient synthesis of 3-aryl-4-aminocinnolines,,10.1016/0040-4039(95)00005-w,1995-02-01,0.592000727809857
Organic Letters,A Synthesis Strategy for the Production of a Macrolactone of Gulmirecin A via a Ni(0)-Mediated Reductive Cyclization Reaction,"A synthesis strategy for the production of a key synthetic intermediate of gulmirecin A was described. The key reaction in the preparation of the 12-membered macrolactone is the Ni(0)-mediated reductive cyclization reaction of ynal using an N -heterocyclic carbene ligand and silane reductant. In addition, the α-selective glycosylation reaction of the macrolactone was performed to demonstrate the synthesis of gulmirecin and disciformycin precursors.",10.1021/acs.orglett.0c00665,2020-03-12,0.5920006602408004
Synthesis,A Novel and Efficient Synthesisof Camphorquinone from Camphoric Acid,"Camphorquinone (1), an important finechemical and medicinal product derived from camphor, was efficientlysynthesized from easily available camphoric acid (2).The key steps include acyloin condensation using Me3SiClas a scavenger of alkoxides and oxidation of the bis(trimethylsilyl)derivative 4 by bromine in CCl4.The new method offers an efficient alternative synthesis of camphorquinone(1).",10.1055/s-2003-41001,2003-01-01,0.5919809707512941
Synlett,The Total Synthesis of Hyperforin,"Hyperforin has remained a popular and challenging synthetic target since its isolation over forty years ago. As a result, numerous synthetic strategies and ring-forming reactions have been developed to address its formidable molecular architecture. Herein we describe our contributions to this area resulting in a ten-step synthetic pathway enabled by a novel diketene annulation reaction and oxidative ring expansion strategy.",10.1055/s-0035-1561619,2016-04-20,0.5919639620624885
Synlett,Total Synthesis of the Caged Diterpenoid Atropurpuran,"Abstract In this account, we wish to share some stories behind our 13-step synthesis of the caged complex diterpenoid atropurpuran. Although our approach might appear to have proceeded smoothly, the unraveling of the core-construction puzzle and late-stage decorations was full of drama. 1 Introduction 2 Total Synthesis of Atropurpuran 3 Conclusion",10.1055/a-1984-0686,2022-11-22,0.5919547848750085
Synthesis,A General and Simple Route to the Synthesis of Triptycenes,"All articles of this category A general and simple route to the synthesis of the triptycene derivatives 5,12-dihydro-5,12[1′,2′]-benzenonaphthacene (1) , 5,14-dihydro-5,14[1′,2′]-benzenopentacene (2) and 5,16-dihydro-5,16[1′,2′]-benzenohexacene (3) is described. It involves the cycloaddition of appropriate quinone to anthracene and subsequent treatment of the resulting adduct with lithium aluminium hydride, followed by p - toluenesulfonyl chloride in pyridine.",10.1055/s-1991-26547,1991-01-01,0.5919520379914015
Synlett,A Practical and Controllable Enantioselective Synthesis of 2-Phenyl-1-cyclopropanecarboxylates via a Camphor-Derived Sulfonium Ylide,"We have developed a practical and controllable enantio­selective synthesis of 2-phenyl-1-cyclopropane-carboxylates via camphor-derived sulfonium ylide. The procedure has many advantages such as cheap starting materials, facile synthetic procedures, good yields, excellent diastereoselectivities and high enantioselectivities.",10.1055/s-2005-869852,2005-06-07,0.5919482572368457
Organic Process Research & Development,"Process for the Preparation of an Amorphous, Peptide-like Diabetes Drug: Approach to a Chromatography-Free Process","A manufacturing process suitable for large-scale production of the peptide-like amorphous compound N -((2 R )-1-{(3 R )-6-chloro-3-[(dimethylamino)methyl]-3,4-dihydroquinolin-1(2 H )-yl}-3-(1 H -indol-3-yl)-1-oxopropan-2-yl)-1-[(1-methyl-1 H -indol-2-yl)carbonyl]piperidine-4-carboxamide (1) as a drug for treating diabetes has been developed. The first kilogram quantities of 1 were prepared via a single-chromatography process that employed recyclable cation-exchange resin chromatography for an amorphous intermediate (2 R )-2-amino-1-[(3 R )-6-chloro-3-[(dimethylamino)methyl]-3,4-dihydroquinolin-1(2 H )-yl]-3-(1 H -indol-3-yl)-propan-1-one ( syn - 3a ). We have also developed a chromatography-free process that involves a combination purification of extraction of syn - 3a with crystallization of syn - 3a ·0.25H 3 PO 4 ·0.5H 2 O. The latter process afforded amorphous compound 1 with >98% purity by HPLC area analysis, the same quality as that provided by the former process.",10.1021/op100084r,2010-07-23,0.5919448089989823
Organic Process Research & Development,An Improved Synthesis of Etravirine,"Etravirine ( 1 ) is a novel diarylpyrimidine non-nucleoside reverse transcriptase inhibitor and has recently been approved by the U.S. Federal Drug Administsration for the treatment of AIDS. Its reported synthesis is fraught with many difficulties, the foremost being the poor yield and long reaction time required at the aminolysis stage. We attributed this problem to the presence of a bromide group adjacent to the reaction site of the advance intermediate ( 6 ). In order to circumvent this issue, we proposed to defer the installation of the bromide group at a later stage, preferably after aminolysis. Indeed, this protocol has worked well. However, in the process of installation of diarylether and diarylamine functionalities at appropriate positions, we had to reverse the sequence of displacement reactions of the dichloride intermediate ( 9 ) with 3,5-dimethyl-4-hydroxybenzonitrile ( 5 ) and 4-aminobenzonitrile ( 3 ). The classical bromination led to the completion of etravirine synthesis.",10.1021/op9003289,2010-04-21,0.5919350085960415
Tetrahedron,Chiral zinc homoenolate of methyl isobutyrate. A new building block for the synthesis of chiral α-methylesters,,10.1016/s0040-4039(00)95722-8,1987-01-01,0.5919333874682391
Angewandte Chemie International Edition,Palladium‐Catalyzed DYKAT of Vinyl Epoxides: Enantioselective Total Synthesis and Assignment of the Configuration of (+)‐Broussonetine G,A potential general approach to potent N-heterocyclic glycosidase inhibitors is illustrated by the first total synthesis of (+)-broussonetine G (1). The key transformation of the synthesis relies on two successive palladium-catalyzed asymmetric allylic alkylations of butadiene monoxide with a nitrogen nucleophile to construct the pyrrolidine core.,10.1002/anie.200352857,2003-12-10,0.5919324377968594
Journal of Organic Chemistry,"Novel Dendritic α-Sialosides:  Synthesis of Glycodendrimers Based on a 3,3‘-Iminobis(propylamine) Core","The cluster or multivalent effect has been recognized as an effective means by which to increase binding interactions between carbohydrates and proteins. In fact, it has been demonstrated that sialylated multibranched L-lysine dendrimers were potent inhibitors of hemagglutination of human erythrocytes by Influenza viruses. In a continuation of these studies, the synthesis of novel glycodendrimers with even valencies from 2 to 16 and ending with equidistant thiosialoside residues is described. These symmetrical dendrimers were more readily characterized by standard NMR spectral techniques than previously reported nonsymmetrical dendrimers of this general type. The synthesis of the dendritic core was based on the regioselective protection of the primary amines of 3,3'-iminobis(propylamine) (4) using benzyl cyanoformate. The resulting secondary amine 5 was alkylated with tert-butyl bromoacetate to provide divalent core structure 6 with Cbz protected amines and acid protected tert-butyl ester. Sequential deprotection by trifluoroacetolysis or hydrogenation afforded acid 7 or diamine 8 as key precursors, respectively. The two fragments were coupled using HOBt/DIC strategy to provide Cbz-protected dendrimers with valencies of 2, 4, 8, and 16 in the first, second, third, and fourth generations, respectively, in reasonable to good yields (42-82%). Cbz-protected precursors were efficiently transformed into N-chloroacetylated dendrimers by hydrogenolysis and treatment of the resulting amines with chloroacetic anhydride (82-91%). N-Chloroacetylated dendrimers were then treated with an excess of 2-thiosialic acid derivative 3 to give fully protected sialodendrimers in 76-96% yields. Deprotection of sialodendrimers under Zemplén conditions followed by methyl ester saponification and purification by gel permeation chromatography afforded symmetrical dendritic alpha-thiosialosides 21, 23, 25, and 27 in fair yields (47-58%). These novel sialodendrimers, in keeping with their design, are currently being evaluated as inhibitors of human erythrocyte hemagglutination by Influenza viruses.",10.1021/jo961047z,1996-01-01,0.5919306519373438
Synlett,Palladium Catalyzed Polyene Cyclizations: An Approach to the Pentacyclic Carbon Framework of Halenaquinone and Xestoquinone,"(opens in new window) Buy Article (opens in new window) Permissions and Reprints (opens in new window) All articles of this category (opens in new window) A seven step synthesis of the pentacyclic framework of xestoquinone and halenaquinone is described beginning with 3-(hydroxymethyl)furan and 3-bromo-2-naphthoyl chloride utilizing, as the key step, a palladium catalyzed polyene cyclization.",10.1055/s-1994-22950,1994-01-01,0.591929263037683
Organic Process Research & Development,"The Synthesis of the High-Potency Sweetener, NC-00637. Part 1:  The Synthesis of (<i>S</i>)-2-Methylhexanoic Acid","The synthesis of the high potency sweetener candidate NC-00637 ( 1 ) required large quantities of ( S )-2-methylhexanoic acid ( 2 ). This acid was first prepared in small quantities by the use of chiral auxiliaries. For large quantities, resolution by classical means and an enzymatic method were investigated. Asymmetric hydrogenation provided a workable solution.",10.1021/op025616i,2003-04-18,0.5919282971139501
Organic Letters,Biomimetic Total Synthesis of Gracilioethers B and C,"Total syntheses of the marine polyketide metabolites gracilioethers B and C have been realized in 9 steps (40% overall yield) and 10 steps (34% overall yield), respectively. The [2(5H)-furanylidene]ethanoate (furanylidene) motif was constructed in a transacetalization/dehydration cascade of an advanced β-ketoester intermediate, which was designed to mimic a postulated biosynthetic precursor to the natural products. The relative and absolute configurations of gracilioethers B and C are confirmed as (6R,8R) and (6R,8R,11S), respectively.",10.1021/ol503695j,2015-01-26,0.5919229463578306
European Journal of Organic Chemistry,"Enantioselective Total Syntheses of (<i>R</i>)‐ and (<i>S</i>)‐Naphthotectone, and Stereochemical Assignment of the Natural Product","Abstract Both isomers of naphthotectone, an isoprenoid quinone from Verbenaceae Tectona grandis possessing interesting biological activities, were enantioselectively obtained by two different synthetic routes in which the carbon side‐chain of the naphthoquinone core was introduced using either a Sonogashira or a Heck coupling reaction. In both cases, the naphthoquinone core of the final products was obtained by a late‐stage anodic treatment. ( R )‐Naphthotectone was obtained in six steps from leuconaphthazarin with an overall yield of 38 % and an enantiomeric excess of 86 %. This compound was found to have the same absolute configuration as the natural product at its C‐3′ stereogenic center. ( S )‐Naphthotectone was obtained in five steps from leuconaphthazarin with an overall yield of 36 % and an enantiomeric excess of 80 %.",10.1002/ejoc.201501479,2016-02-17,0.591922049335183
Tetrahedron,Synthesis of the tricyclic triamine core of martinelline and martinellic acid,,10.1016/s0040-4039(99)00461-x,1999-04-01,0.5919219342440355
European Journal of Organic Chemistry,Total Synthesis of (±)‐Scopolamine: Challenges of the Tropane Ring,"Abstract Scopolamine was synthesized using 6,7‐dehydrotropine as a key intermediate. Rhodium‐catalyzed [4 + 3] cycloaddition chemistry and a modified Robinson–Schöpf reaction were each independently evaluated for their utility in constructing the tropane core. Both synthetic approaches gave comparable overall yields.",10.1002/ejoc.201501430,2016-01-29,0.5919163664410512
Synthesis,A New Synthetic Route to Isoquinolin-1(2H)-one Derivatives from 3-Hydroxyphthalides,All articles of this category A new synthetic route for the conversion of substituted 3-hydroxyphthalides into the corresponding isoquinolin-1(2 H )-one was established. This method can be applied to the preparation of isoquinolin-1(2 H )-ones with electron-withdrawing groups that are relatively difficult to synthesize by conventional procedures. A convenient synthesis of isoquinolones from 3-hydroxyphthalides is reported.,10.1055/s-1995-3927,1995-04-01,0.5919131848460373
Journal of Organic Chemistry,Synthesis and Characterization of Fluorescent Poly(aromatic amide) Dendrimers,"The synthesis of a series of poly(aromatic amide) dendrimers up to the second generation is described herein. The AB(2) building block used throughout the synthesis of the dendrimers was the allyl ester of 3,5-diaminocinnamic acid, which has been synthesized from 3,5-dinitrobenzoic acid in good yield with use of a four-step procedure. Dendron synthesis was achieved via a convergent approach with use of a sequence of deprotection/coupling steps. Two commercially available alcohols, L-menthol and citronellol, were coupled to the AB(2) monomer by using an alkyl diacid spacer and two core units; 1,7-diaminoheptane and tris(2-aminoethyl)amine have been used to produce the final dendrimers. Characterization was carried out by NMR and IR spectroscopies, MALDI-TOF mass spectrometry, GPC, and DSC. The novel monomer and dendritic derivatives exhibited a strong fluorescence emission in the visible region (lambda approximately 500 nm) of the spectrum and a weak emission in the near-infrared (lambda approximately 850 nm) upon excitation in the near-UV region. The fluorescence emission characteristics were found to be solvent and dendrimer generation dependent.",10.1021/jo048799a,2004-11-26,0.5919126809526722
Synthesis,Synthesis of Racemic and Enantiopure 2-Alkylsulfinyl Dithioacetates and Thioacetamides,"All articles of this category New 2-alkylsulfinyl dithioacetates and thioacetamides have been prepared. The asymmetric synthesis of ( R )-2-(cyclohexylsulfinyl)- N , N -dimethylthioacetamide from previously unreported ( S )-diacetone-d-glucose cyclohexanesulfinate was achieved in excellent yield (91%) and enantiomeric excess (98%). Methyl ( R )-2-(cyclohexylsulfinyl)dithioacetate (98% ee) was obtained from chiral cyclohexyl methyl sulfoxide (99% ee). sulfoxide - thioamide - dithioester - asymmetric synthesis - chiral sulfinate",10.1055/s-1999-3447,1999-04-01,0.5919102901084541
Tetrahedron,AN ENANTIOSPECIFIC NITRONE CYCLOADDITION ROUTE TO 3-HYDROXY-2-AZETIDINONES,,10.1016/s0040-4039(97)00394-8,1997-04-01,0.5919065597948475
Tetrahedron,An efficient and stereocontrolled synthesis of the nephritogenoside core structure,,10.1016/0040-4039(91)80430-e,1991-11-01,0.5919023643991445
Tetrahedron,"Stereoselective synthesis of 5-methylphosphono-D-arabino hydroximolactone, inhibitor of glucosamine-6-phosphate synthase and phosphoglucose isomerase",,10.1016/s0040-4039(97)10514-7,1998-01-01,0.5918964241943805
Tetrahedron,Efficient synthesis of 2-arylamino substituted pyridinyl nitriles by Buchwald–Hartwig amination,,10.1016/j.tetlet.2013.03.085,2013-03-26,0.5918872925194596
Journal of the American Chemical Society,A Practical Synthesis of (+)-Discodermolide and Analogues: Fragment Union by Complex Aldol Reactions,"A practical stereocontrolled synthesis of (+)-discodermolide (1) has been completed in 10.3% overall yield (23 steps longest linear sequence). The absolute stereochemistry of the C(1)-C(6) (7), C(9)-C(16) (8), and C(17)-C(24) (9) subunits was established via substrate-controlled, boron-mediated, aldol reactions of the chiral ethyl ketones 10, 11, and 12. Key fragment coupling reactions were a lithium-mediated, anti-selective, aldol reaction of aryl ester 8 (under Felkin-Anh induction from the aldehyde component 9), followed by in situ reduction to produce the 1,3-diol 40, and a (+)-diisopinocampheylboron chloride-mediated aldol reaction of methyl ketone 7 (overturning the inherent substrate induction from the aldehyde component 52) to give the (7S)-adduct 58. The flexibility of our overall strategy is illustrated by the synthesis of a number of diastereomers and structural analogues of discodermolide, which should serve as valuable probes for structure-activity studies.",10.1021/ja011211m,2001-09-05,0.5918839984530194
Organic Process Research & Development,Development of an Efficient Pd-Catalyzed Coupling Process for Axitinib,"The manufacturing process of axitinib ( 1 ) involves two Pd-catalyzed coupling reactions, a Migita coupling and a Heck reaction. Optimization of both of these pivotal bond-formation steps is discussed as well as the approach to control impurities in axitinib. Essential to the control strategy was the optimization of the Heck reaction to minimize formation of impurities, in addition to the development of an efficient isolation of crude axitinib to purge impurities.",10.1021/op400088k,2013-05-24,0.591880787897979
Journal of Organic Chemistry,Desymmetrization of Benzoic Acid in the Context of the Asymmetric Birch Reduction−Alkylation Protocol. Asymmetric Total Syntheses of (−)-Eburnamonine and (−)-Aspidospermidine,"The highly diastereoselective potassium in ammonia reduction−ethylation (EtI) of the chiral 2-(trimethylsilyl)benzamide 1b to give 1,4-cyclohexadiene 3 is the key step in asymmetric syntheses of (−)-eburnamonine ( 4 ) and (−)-aspidospermidine ( 5 ). Cyclohexadiene 3 was converted to cyclohexanone 7, which provided the trimethylsilyl-substituted butyrolactone 9 utilized for the synthesis of 4 and butyrolactone 13 required for the synthesis of 5 . The preparation of 9 depended upon the completely regioselective silicon-directed Baeyer−Villiger oxidation 7 → 8; Baeyer−Villiger oxidation of the cyclohexenone 10 also was regioselective to give the desired enol lactone 11 in 92% yield. Remarkable diastereoselectivity was observed for the kinetically controlled cyclization of the acyl imminium ion derived from the vinyl-substituted carboxaldehyde 16b; treatment of 16b with 5 equiv of CF 3 CO 2 H in CH 2 Cl 2 at −55 °C gave an 18:1 mixture of 17 and its C(3) β-epimer in 93% yield. The oxidation of alcohol 18 containing sensitive indole and piperidine rings was best carried out with tetrapropylammonium perruthenate/ N -methylmorpholine N -oxide to give (−)-eburnamonine ( 4 ) in 97% yield. The asymmetric synthesis of (−)-aspidospermidine 5 involved the conversion of butyrolactone 13 to the hydroxylactam 22, the Harley-Mason cyclization of 22 to 23, and reduction of 23 with LiAlH 4 .",10.1021/jo9707592,1997-10-01,0.5918747962666879
Organic Letters,Synthesis of the Common Core Structure of the Stemofoline Alkaloids,"A novel synthetic route to the common core structural motif of the stemofoline alkaloids has been developed. The key transformations include (1) an intramolecular 1,3-dipolar cycloaddition reaction of a highly functionalized nitrone, (2) the subsequent formation of a caged structure via lithiated allylic sulfoxide, and (3) the concomitant sila-Pummerer reaction of α-silylalkenyl sulfoxide to prepare a thioester precursor. A series of stereochemistries on the highly caged core structure characteristic of the stemofoline alkaloids was successfully assembled.",10.1021/acs.orglett.5b02373,2015-09-16,0.5918705855690709
Synthesis,"Synthesis and Deamination of 1,4-Dihydronaphthalen-1,4-imines: A Convenient Naphthalene Synthesis",,10.1055/s-1983-30404,1983-01-01,0.5918696869657641
Synlett,"A Convenient Synthesis of 1,5-Dialkyl-1,2,3,4-tetrahydropyridines. Synthons for Alkaloid Synthesis",,10.1055/s-1991-20727,1991-01-01,0.5918696869657641
Journal of Organic Chemistry,Preparation of Carbocyclic<i>S</i>-Adenosylazamethionine Accompanied by a Practical Synthesis of (−)-Aristeromycin,"For the preparation of a carbocyclic nitrogen analogue of S-adenosylmethionine (carba-AdoazaMet, 4), a practical synthesis of (-)-aristeromycin (7) has been developed using variations of literature procedures. This approach called for a stereospecific synthesis of (3aR,6aR)-2,2-dimethyl-3a,6a-dihydrocyclopenta[1,3]dioxol-4-one ((4R, 5R)-4,5-O-isopropylidene-2-cyclopentenone) (8), which was achieved by modifying reported procedures from D-(-)-ribose.",10.1021/jo040119g,2004-05-01,0.5918694504398214
Tetrahedron,New synthetic strategy for chiral 2-oxazolidinones derivatives via rhodium-catalyzed asymmetric hydrogenation,,10.1016/j.tetlet.2015.12.105,2015-12-29,0.5918627338918622
Tetrahedron,Visible-light photoredox-promoted desilylative allylation of α-silylamines: An efficient route to synthesis of homoallylic amines,,10.1016/j.tetlet.2021.153357,2021-08-27,0.5918517326342925
Tetrahedron,Three-component coupling strategy for the expeditious synthesis of novel 4-aminobenzoxazinone N-nucleosides,,10.1016/j.tetlet.2005.11.006,2005-11-21,0.591848705503248
Organic Letters,Catalytic Asymmetric Synthesis of (+)-Anthecotulide Using Enyne and Meyer–Schuster Rearrangements,"The bioactive sesquiterpene lactone (+)-anthecotulide (1) is synthesized for the first time, in a six-step sequence devoid of protecting groups. The key transformations are a novel Rh(I)-catalyzed asymmetric enyne rearrangement of a terminal alkynyl ester (4), to form the α-methylene-γ-butyrolactone core, and a final-step mild Au(I)-catalyzed Meyer-Schuster rearrangement.",10.1021/ol202425e,2011-10-07,0.5918394750161129
Tetrahedron,Synthesis of novel crown derivatives incorporating a diaminophosphine group in a polyether macrocycle,,10.1016/s0040-4039(00)95540-0,1987-01-01,0.5918330629190515
Synlett,A Simple Enantioselective Synthesis of (-)-<i>S</i>- and (+)-<i>R</i>-Camphonanic Acids,"All articles of this category A four step enantioselective synthesis of 1 S - and 1 R -1,2, 2-trimethylcyclopentanecarboxylic acids [( S )- and ( R )-camphonanic acid, (-)- 1 and (+)- 1 respectively] has been achieved from ß-cyclogeraniol, using a Katsuki-Sharpless asymmetric epoxidation and a pinacollic rearrangement as key synthetic steps.",10.1055/s-1993-22642,1993-01-01,0.5918285957411462
Organic Letters,Formal Synthesis of (±)-Guanacastepene A:  A Tandem Ring-Closing Metathesis Approach,"A concise route to a key intermediate in the total synthesis of guanacastepene A is described. The main features include the simultaneous construction of the seven- and six-membered rings, using a tandem ring-closing metathesis and a stereoselective introduction of the oxygenated function at the C5 position. [reaction: see text]",10.1021/ol049452x,2004-05-01,0.5918267786636878
Tetrahedron,The stereospecific synthesis of a new chiral oxaziridinium salt.,,10.1016/s0040-4039(00)79306-3,1993-11-01,0.5918267448617254
Journal of Organic Chemistry,Synthesis of Withasomnines and Their Non-natural Analogues from Aldehydes and 4-Nitro-1-butanol in Three Steps,"Total synthesis of all three pyrazole-based withasomnine alkaloids and selected examples of their non-natural analogs has been achieved from readily available aldehydes and 4-nitro-1-butanol in three steps. Since 4-nitro-1-butanol in turn is prepared in two steps via Michael addition of nitromethane to acrylate followed by borane reduction of the ester group and the key 1,3-dipolar cycloaddition step is carried out with commercially available TMSCHN2, this approach is a very convenient and economical one.",10.1021/jo400207u,2013-02-25,0.5918199054389849
Tetrahedron,"Synthesis of the new (cyclopenta [b]pyrrolo[1,2-d])azepino[4,5-b]indole ring system",,10.1016/0040-4039(96)01215-4,1996-08-01,0.5918144216338221
Journal of Organic Chemistry,Use of Benzofuran for Concomitant Protection of Aldehyde and Phenol Groups in the Preparation of Mycophenolic Acid Analogues,The use of a benzofuran to mask phenol and arylacetaldehyde moieties simultaneously in the synthesis of analogues of mycophenolic acid (MPA) was explored. Benzofuran 4 provided a stable and easily handled intermediate for the preparation of unnatural derivatives at the C-6 position of MPA. Preparation of the highly potent 6-ethyl MPA analogue 2 was accomplished via aldehyde 2c through this facile route with high-yielding steps and crystalline intermediates.,10.1021/jo0605389,2006-06-01,0.5918120946360194
Synthesis,Thallium(III)-Mediated Ring Contraction of <i>cis</i>-Octalins: An Approach for the Diastereoselective Construction of the <i>nor</i>-Bakkane Skeleton,A new approach for the diastereoselective synthesis of cis-hydrindanes bearing important structural features of the bakkane skeleton is described. The key step in such a sequence is a thallium trinitrate mediated oxidative rearrangement of cis-octalins. The ring-contraction products thus obtained were elaborated in a diastereoselective fashion into hydrindanes bearing a quaternary center.,10.1055/s-2006-942500,2006-08-01,0.5918092833917965
Angewandte Chemie International Edition,<i>Exo</i> ‐Selective Intramolecular (4+3) Cycloadditions to <i>Trans</i> ‐Fused Perhydroazulenes: An Asymmetric Formal Synthesis of (−)‐Pseudolaric Acid B,"We present an asymmetric formal total synthesis of pseudolaric acid B (PAB), based on the intramolecular (4+3) cycloaddition of a new class of epoxy enolsilane substrates. This substrate type has the epoxide geminally-substituted on the tether to the furan, which reacts to yield the trans-fused perhydroazulene core of PAB containing the quaternary stereocenter. The reaction is highly diastereoselective, as opposed to cycloadditions of previous substrate types that generate the perhydroazulene framework. The role of the geminal tether in controlling the transition state conformation and the exo-selectivity is revealed by density functional theory calculations. Using this intramolecular cycloaddition as the key reaction, together with several one-pot sequences, a key intermediate in Trost's synthesis of PAB was accomplished, representing the shortest asymmetric synthesis of this anti-tumor natural product thus far.",10.1002/anie.202509650,2025-08-05,0.5917992747347373
Organic Letters,Anodic Coupling Reactions:  A Sequential Cyclization Route to the Arteannuin Ring Skeleton,"A pair of intramolecular anodic olefin coupling reactions has been used to construct the arteannuin ring skeleton. Both coupling reactions took advantage of a furan ring as one of the coupling partners. In the first, it was found that an enol ether derived from an aldehyde was not an effective initiating group for the reaction. Instead, the cyclization benefited strongly from the use of a N,O-ketene acetal initiating group. In the second cyclization, an endocyclic enol ether was coupled to the furan ring. This second electrolysis reaction generated the key tetrasubstituted carbon at the center of the arteannuin ring skeleton.",10.1021/ol702118n,2007-10-01,0.5917974419345994
European Journal of Organic Chemistry,Synthesis of Ellipticine by Hetaryne Cycloadditions − Control of Regioselectivity,"We have modified Gribble’s and Moody’s approaches to ellipticines by introducing substituents into the 3,4-didehydropyridine dienophile to control the key cycloaddition step. A chloro substituent at position 2 improved the yields and the regioselectivities of the cycloadditions and the overall efficiency of the synthesis of ellipticine.",10.1002/1099-0690(200112)2001:23<4543::aid-ejoc4543>3.0.co;2-#,2001-11-07,0.5917958527158125
Tetrahedron,"Synthesis of 5-amino-5-deoxy-α-D-allofuranuronic acid derivative, a sugar component of polyoxins synthesis in nucleoside antibiotics, part VII",,10.1016/s0040-4039(01)96368-3,1971-01-01,0.591793864827226
Organic Letters,Stereoselective Total Synthesis of (−)-Depudecin,"The total synthesis of the natural product depudecin, an antiangiogenic microbial polyketide with inhibitory activity against histone deacetylases, is reported. Characterized by a highly oxidized 11-carbon chain containing two epoxides conjugated through a trans-disubstituted olefin, its total synthesis was efficiently accomplished by a novel asymmetric methodology of epoxide formation based on a new class of chiral sulfonium salts, allowing for the construction of the oxirane rings in an efficient and stereoselective fashion.",10.1021/acs.orglett.5b02697,2015-10-30,0.5917923831714023
Organic Process Research & Development,An Improved and Efficient Process for the Preparation of Tofacitinib Citrate,"The present invention is related to a simple and efficient process for the preparation of tofacitinib citrate 1, a Pfizer molecule approved for the treatment of rheumatoid arthritis. The process relies upon an improved process for the preparation of a key intermediate (3 R,4 R )-(1-benzyl-4-methylpiperidin-3-yl)methylamine as tartarate salt 3 and its simple and impurity-free conversion to tofacitinib citrate 1 . The current invention is aimed at addressing process development issues related to quality and yields. The disclosed process is capable of delivering much higher yield compared to the prior state-of-the-art process and is able to yield very highly pure compound.",10.1021/op500274j,2014-11-17,0.5917900346514914
Tetrahedron,"An improved synthesis of (4S,5S)-2,2-dimethyl-4-phenyl-1,3-dioxan-5-amine",,10.1016/s0040-4039(01)81669-5,1984-01-01,0.591783511354496
European Journal of Organic Chemistry,Flexible Routes to the 5‐Hydroxy Acid Fragment of the Cryptophycins,"Abstract Two solutions to establishing the anti stereochemistry of the vicinal stereocenters in the 5‐hydroxy acid subunit of cryptophycin, based on initial Evans syn aldol reactions between an N ‐(propionyl)oxazolidinone 4 and a C 3 aldehyde, were developed. In the first route, the secondary hydroxy group was inverted by use of Mitsunobu reaction conditions, whereas the second route features an inversion of the methyl‐bearing stereocenter, achieved by reductive removal of the chiral auxiliary, elimination to afford the terminal alkene, and anti ‐selective hydroboration. The aryl part can be attached either by Wittig−Horner olefination or by a modified Julia coupling. Both routes provide the hydroxy acid 16 in a very efficient manner. The substrate for the hydroboration, alkene 22 , could also be obtained from ( S )‐malic acid. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2003)",10.1002/ejoc.200210695,2003-04-17,0.5917811402263906
Journal of Organic Chemistry,Enantioselective Synthesis of <i>trans</i>-4-Methylpipecolic Acid,"An asymmetric synthesis for the preparation of both enantiomers of trans-methylpipecolic acids is described. It is based on Sharpless epoxidation as a chirality source, regioselective ring opening with allylamine, and ring-closing metathesis to construct the piperidine ring. The stereogenic center at C-4 is set by stereoselective hydrogenation that is directed by the alcohol functionality of an intermediate and proceeds with good diastereomeric control (trans/cis 16/1). Crystallization of the Boc-protected amino acid afforded the target products with excellent chemical (98% de) and enantiomeric purity (99% ee).",10.1021/jo071220z,2007-09-01,0.5917776010923145
Journal of the American Chemical Society,"Studies Directed to the Synthesis of the Unusual Cardiotoxic Agent Kalmanol. Enantioselective Construction of the Advanced Tetracyclic 7-Oxy-5,6-dideoxy Congener","The first synthesis of a highly functionalized B-homo-C-nor grayanotoxin closely related to kalmanol is reported. An enantiocontrolled route to the diquinane sector was first developed from (4 R )-(+)- tert -butyldimethylsiloxycyclopentenone by taking advantage of the Michael acceptor properties of this enone and an α,β-unsaturated ester subsequently derived from it, viz., 4 → 7 → 8 . These experiments formed the basis for more advanced substitution of the bicyclo[3.3.0]octane core. In fact, ready access was gained to the α-hydroxy esters 24 − 27 . In these advanced intermediates, it is imperative that the acetyl and carbomethoxy groups bear a trans 1,3-relationship. The neighboring OR substituent should preferably be larger than methoxy in order to guarantee 100% facial selectivity during the ensuing capture by 1 (as its lithiated derivative). This condensation leads unidirectionally to tricyclic lactones represented by 30 and 31 and sets the stage for implementation of sequential Tebbe olefination and Claisen rearrangement. This pivotal two-step process gives rise directly to the targeted tetracyclic framework. The further oxygenation of 35 can be accomplished in a highly stereoselective manner to give 3 . The characteristics of the [3.3] sigmatropic event that results in ring expansion plays a significant role in defining absolute configuration at key carbon centers which would otherwise be difficult to establish unequivocally. A total of 25 synthetic steps was involved.",10.1021/ja9533454,1996-01-01,0.5917740398137926
Tetrahedron,Studies towards total synthesis of antillatoxin: Synthesis of C1C11 fragment,,10.1016/s0040-4039(97)10827-9,1998-03-01,0.5917729101251142
Tetrahedron,(π-Allyl)palladium coupling of 2-(tributylstannyl)cyclopent-2-enone for the synthesis of jasmonoid analogs,,10.1016/j.tetlet.2017.04.018,2017-04-08,0.5917663139889751
Synlett,"A Convenient Synthesis of 1,5-Dialkyl-1,2,3,4-tetrahydropyridines. Synthons for Alkaloid Synthesis","All articles of this category 1,5-Dialkyl-1,2,3,4-tetrahydropyridines, which are useful building blocks for alkaloid synthesis, are easily accesible from novel δ-chloroaldimines ( N -alkyl/ N -cycloalkyl-5-chloro-2-methylpentanimines). The synthetic strategy involves a straightforward construction of the title heterocycles from simple aldehydes via imination to aldimines, α-alkylation with 1-bromo-3-chloropropane to afford δ-chloroaldimines and ring closure with sodium isopropoxide.",10.1055/s-1991-34724,1991-01-01,0.5917610737736553
Organic Letters,Asymmetric Synthesis of <i>N</i>-Boc-(<i>R</i>)-Silaproline via Rh-Catalyzed Intramolecular Hydrosilylation of Dehydroalanine and Continuous Flow <i>N</i>-Alkylation,"An asymmetric synthesis of a silicon-containing proline surrogate, N-Boc-(R)-silaproline (1), is described. Starting from N-Boc-dehydroalanine ester, deprotonation, followed by N-alkylation with chloromethyldimethylsilane under flow conditions, afforded the N-alkylated product 8 in 91% yield. An unprecedented enantioselective (NBD)2RhBF4/Josiphos 404-1 catalyzed 5-endo-trig hydrosilylation afforded the silaproline ester in 85-90% yield and >95% ee. Subsequent saponification and salt formation upgraded 1 to >99% ee.",10.1021/acs.orglett.6b00548,2016-03-25,0.5917552086748202
Green Chemistry,An expedient four-component domino protocol for the synthesis of novel benzo[a]phenazine annulated heterocycles and their photophysical studies,"A new one pot two-step domino protocol for the efficient synthesis of novel fluorescent benzo[a]phenazine fused derivatives has been developed. The synthesis was achieved by reacting 2-hydroxynaphthalene-1,4-dione, ortho-phenylenediamines, aromatic aldehydes and cyclic 1,3-dicarbonyl compounds in the presence of a catalytic amount of p-TSA in PEG-400 at 70 °C. The structural assignment has been unambiguously confirmed by X-ray analysis. The present finding provides an efficient and promising synthetic strategy for the synthesis of libraries with functional group diversity.",10.1039/c2gc35644a,2012-01-01,0.591752403253411
Tetrahedron,A practical synthesis of the lipophilic side chain of the polyoxypeptins,,10.1016/s0040-4039(01)00205-2,2001-03-01,0.5917522203722411
Tetrahedron,A novel homolytic substitution on vinylic carbon. A new route to vinyl stannane,,10.1016/s0040-4039(00)83980-5,1986-01-01,0.5917518879767124
Organic Letters,New Synthetic Methodology for the Construction of 7-Substituted Farnesyl Diphosphate Analogs,"Through the use of a 1,2-metalate rearrangement, six 7-substituted farnesol analogs were generated in a concise manner. This new synthetic route allowed us to quickly prepare several diverse farnesyl diphosphate analogs with interesting biological activities against mammalian protein-farnesyl transferase.",10.1021/ol201069x,2011-06-23,0.591746083100962
Journal of Organic Chemistry,"Development of a Crystallization-Induced Diastereomer Transformation of Oxime Isomers for the Asymmetric Synthesis of (1<i>S</i>,6<i>R</i>)-3,9-Diazabicyclo[4.2.1]nonane","Herein we report a practical crystallization-induced diastereomer transformation (CIDT) of oxime isomers for the scalable asymmetric synthesis of the bicyclic diamine (1 S,6 R )-3,9-diazabicyclo[4.2.1]nonane derivative that serves as a valuable building block in medicinal chemistry. The developed approach utilizes ( S )-phenylethylamine as a chiral auxiliary handle for CIDT, and the starting nortropinone derivative is prepared in one step from commercially available materials. The resulting E -oxime is subjected to a stereospecific Beckmann rearrangement, followed by reduction of the resulting lactam with LiAlH 4 to afford the monoprotected (1 S,6 R )-3,9-diazabicyclo[4.2.1]nonane derivative. The development of the CIDT and understanding of the mechanistic implications leading to the high selectivity are reported.",10.1021/acs.joc.3c01228,2023-08-23,0.5917434972381486
Synthesis,Facile Synthesis of (<i>S</i>)-Gizzerosine - A Potent Inducer of Gizzard Erosion in Chicks - Using Successive Zinc-Mediated and Palladium-Catalyzed Coupling Reactions,"Gizzerosine, a potent inducer of gizzard erosion in chicks, was synthesized using successive zinc-mediated and palladium-catalyzed coupling reactions as the key steps. The piperonyl moiety was used as a novel N-protecting group.",10.1055/s-2005-918447,2005-01-01,0.5917359995572566
Organic Letters,Enantioselective Total Syntheses of (−)-Silicine and (−)-20-Episilicine,"The enantioselective total syntheses of (−)-silicine and (−)-20-episilicine, which contain a chiral piperidine with three contiguous chiral centers ( D -ring) and a strained seven-membered ring ( C -ring) attached to an indole, were achieved. The key steps of these syntheses included a chiral secondary amine-catalyzed formal aza-[3 + 3] cycloaddition reaction and Lewis acid-mediated irreversible ring-closing reaction. In addition, the stereochemistry at C20 was controlled at a later stage in the syntheses.",10.1021/acs.orglett.3c02590,2023-09-11,0.5917310409996229
Journal of Organic Chemistry,Heck Cyclization Strategy for Preparation of Erythrinan Alkaloids: Asymmetric Synthesis of Unnatural (−)-Erysotramidine from<scp>L</scp>-Tartaric Acid,"With an imide derived from L-tartaric acid as the starting material, ent-erysotramidine was synthesized for the first time. The synthesis features the use of the enantiopure synthon, prepared in a set of highly stereoselective reactions, including N-acyliminium cyclization, dihydrofuranyl ring formation via silver-catalyzed intramolecular alcohol addition to acetylene, and vinyl ether catalytic hydrogen reduction. The crucial step of the synthesis, assembly of ring A, was achieved by using Heck cyclization of (Z)-iodoolefin.",10.1021/jo5026157,2015-01-08,0.5917257341122295
Tetrahedron,An efficient copper(II)-catalyzed synthesis of benzothiazoles through intramolecular coupling-cyclization of N-(2-chlorophenyl)benzothioamides,,10.1016/j.tetlet.2010.07.079,2010-07-20,0.5917248307627502
Organic Process Research & Development,A Practical Synthetic Method of <i>O</i>-(2-(Pyrazol-1-yl)pyridin-5-yl)methylhydroxylamine as a Component of Modithromycin,"A practical synthesis of O -(2-(pyrazol-1-yl)pyridin-5-yl)methylhydroxylamine was achieved from the inexpensive raw materials, 2-chloro-5-chloromethylpyridine, pyrazole, and acetone oxime, using common reagents such as aq NaOH and sulfuric acid.",10.1021/op200311q,2011-12-08,0.5917220003023375
Tetrahedron,Studies directed towards the asymmetric total synthesis of antileukemic lignan lactones. Synthesis of optically pure key intermediate and its utility,,10.1016/s0040-4039(01)95395-x,1979-01-01,0.5917168163716202
Journal of Organic Chemistry,Synthesis of 3-Hydroxy-4-arylquinolin-2-ones Including Viridicatol via a Darzens Condensation/Friedel–Crafts Alkylation Strategy,"The new efficient synthesis of biologically important 3-hydroxy-4-arylquinolin-2-ones through the Darzens condensation (epoxidation) of dichloroacetanilides with aromatic aldehydes followed by one-pot dechlorative epoxide-arene cyclization is described. This methodology has been utilized for the synthesis of naturally occurring viridicatol, a fungal metabolite isolated from the penicillium species.",10.1021/acs.joc.8b01871,2018-10-01,0.5917166880467669
Tetrahedron,Facile and practical synthesis of π-extended oxepins by benzannulation and intramolecular cyclization,,10.1016/j.tetlet.2018.12.008,2018-12-03,0.5917065304628241
Tetrahedron,A novel synthesis of (+)-integerrinecic acid lactone from R-(+)-β-citronellol,,10.1016/s0040-4039(00)86693-9,1988-01-01,0.5917037801544323
Tetrahedron,"An efficient synthesis of 13(S)-hydroxy-9Z,11E-octadecadienoic (coriolic) acid.",,10.1016/0040-4039(90)80129-a,1990-01-01,0.5917036049119242
Tetrahedron,A novel biogenetic type synthesis of (+)-hydantocidin,,10.1016/s0040-4039(00)73734-8,1993-09-01,0.591700117008585
Tetrahedron,A novel synthesis of ochotensine-type isoquinolines by thermolysis,,10.1016/s0040-4039(01)94445-4,1972-01-01,0.591700117008585
Tetrahedron,A novel one-pot synthesis of derivatives of aryldioxins and aryldithiins,,10.1016/j.tetlet.2003.12.069,2004-01-16,0.5917000748662643
Organic Letters,"Concise, Asymmetric Total Synthesis of Spirotryprostatin A",[structure: see text] The structurally intriguing cell-cycle inhibitor spirotryprostatin A has been synthesized utilizing an azomethine ylide dipolar cycloaddition reaction as the key step. This pentacyclic alkaloid contains a prenylated tryptophan-derived oxindole moiety that has been created in a regiocontrolled and stereocontrolled manner in a single step.,10.1021/ol0351910,2003-07-22,0.5916971711947034
Journal of Organic Chemistry,Total Synthesis of the Enantiomer of the Furanocembrane Rubifolide,"The total synthesis of 57, the enantiomer of the marine furanocembrane rubifolide (3), is described starting from (S)-(-)-perillyl alcohol (5). The successful route proceeded by oxidative cleavage of 5 to ester aldehyde 30 which was protected, reduced, and homologated to the acetylene 34, the left-hand segment of the synthetic target. Addition to the right-hand aldehyde 39 afforded alcohol 40. The carbonate derivative 41 was converted to the allenylstannane aldehyde 44, which cyclized upon treatment with BF(3).OEt(2). Oxidation with the Dess-Martin periodinane reagent followed by treatment with Et(3)N yielded allenone 45. Allenone 45 cyclized to furan 46 in the presence of catalytic AgNO(3) on silica gel. Brief exposure to p-TsOH effected elimination of the OMOM ether, affording the diastereomeric (Z)-vinylfuran carbonates 47 and 49. Saponification of the former led to alcohol 48, which was converted to the final product by sequential treatment with (CF(3)CO)(2)O, then Pd(PPh(3))(4) and CO in THF-H(2)O, and then AgNO(3) on silica gel. The resulting product, 57, was identical to natural rubifolide on the basis of spectral comparison. The optical rotation was equal and opposite in sign to that of the natural material. A second, but unsuccessful approach is also described.",10.1021/jo970360d,1997-06-01,0.5916961096901876
Angewandte Chemie International Edition,Total Syntheses of Guanacastepenes N and O,The cycloinsertion of cyclohexyne into a pentalene has provided access to the carbon scaffold of the guanacastepenes in nine steps. A late-stage diversifying oxidation of the core structure enabled the synthesis of guanacastepene N and the first total synthesis of guanacastepene O.,10.1002/anie.201007644,2011-03-02,0.5916929945246712
Synlett,Total Synthesis of Mavacuran Alkaloids via Bioinspired and Non-Bioinspired Strategies,"Abstract In this account, we report our endeavors towards the total synthesis of the mavacuran alkaloids and some of their highly natural complex bis-indoles. Our studies started with the hemisynthesis of voacalgine A and bipleiophylline, made an excursion to a related family of monoterpene indole alkaloids (total synthesis of 17-nor-excelsinidine) and ended with the total syntheses of several mavacuran alkaloids (16-epi-pleiocarpamine, 16-hydroxymethylpleiocarpamine, taberdivarine H, normavacurine, C-mavacurine, C-profluorocurine, and C-fluorocurine) via a combination of bioinspired and non-bioinspired synthetic routes. 1 Introduction 2 Bioinspired Hemisynthesis of Voacalgine A and Bipleiophylline 3 Total Synthesis of the Mavacuran Alkaloids 4 Bioinspired Oxidative Cyclization of a Geissoschizine Ammonium Derivative to Form the N1–C16 Bond and the E Ring 5 Non-Bioinspired Michael Addition to Form the C15–C20 Bond and the E Ring 6 Conclusion 7 Epilogue",10.1055/s-0042-1751498,2023-11-02,0.591685622947191
Journal of Organic Chemistry,"FeCl<sub>3</sub>-Mediated One-Pot Domino Reactions for the Synthesis of 9-Aryl/9-Arylethynyl-2,3,4,9-tetrahydro-1<i>H</i>-xanthen-1-ones from Propargylic Amines/Diaryl Amines and 1,3-Cyclohexanediones","An efficient, environmentally friendly and one-pot route to new 9-aryl/9-arylethynyl-2,3,4,9-tetrahydro-1H-xanthen-1-one derivatives from inexpensive starting materials has been developed. This method proceeded by a domino nucleophilic-substitution/intramolecular cyclization/dehydration sequence of propargylic amines/diaryl amines and 1,3-cyclohexanediones under the promotion of FeCl3, which involved the formation of two new σ (C-C and C-O) bonds in a single operation for the construction of novel tetrahydroxanthene skeletons in 68-95% yields.",10.1021/acs.joc.6b00001,2016-02-15,0.5916771640340202
Journal of the American Chemical Society,Biomimetic Total Synthesis of (−)-Erinacine E,"Biomimetic total synthesis of (−)-erinacine E ( 1 ) has been achieved starting from the enantiopure key intermediate, which was prepared via the convergent approach developed by us. The crucial step in this synthesis is an intramolecular aldol reaction driven by the 1,2-migration of a benzoyl group within a compound that was rationally designed to prevent the retro-aldol reaction, thereby successfully providing the strained skeleton of 1 . Considering the structure of a putative biosynthetic intermediate, striatal A, the intramolecular aldol reaction driven by the C4‘ acetyl group could be involved in the biosynthesis of 1 . This acyl group migratory ring-closing reaction could be applied to the synthesis of other strained molecules.",10.1021/ja7102795,2008-01-09,0.5916699592563751
Journal of the American Chemical Society,Total Synthesis of Hybridaphniphylline B,"Hybridaphniphylline B (1) is a Daphniphyllum alkaloid possessing 11 rings and 19 stereocenters. Here we report the first total synthesis of 1 featuring a late-stage intermolecular Diels-Alder reaction of a fully elaborated cyclopentadiene and asperuloside tetraacetate. The diene was prepared on the basis of a scalable route to daphnilongeranin B (4). Claisen rearrangement of an allyl dienol ether was exploited as a key step; the subtle variation of the substrate and use of protic solvents suppressed the undesired Cope rearrangement. Daphniyunnine E (6) and dehydrodaphnilongeranin B (7), two congeners of 4, were also synthesized. The dienophile arose from (+)-genipin through glycosylation and lactonization. A one-pot protocol was developed for the diene formation and Diels-Alder reaction; one of the cycloadducts was converted into 1 through reductive desulfurization and global deacetylation.",10.1021/jacs.8b01681,2018-03-01,0.5916662941158283
Synthesis,6-O-Amino-2-O-carboxymethyl Glucopyranoside as Novel Glycoaminoxy Acid Building Block for the Construction of Oligosaccharide Mimetics,"The synthesis of diversely functionalized carbohydrate building blocks is of great interest towards the generation of new carbohydrate mimetics. Glycoaminoxy acids are recently developed glycoamino acid analogues with both an aminoxy and a carboxyl group connected to the sugar scaffold. These molecules could be readily used for the synthesis of various glycoconjugates through N-oxy amide or oxime bond, thus providing a potent tool for the design of novel functional carbohydrate mimetics. Here, the efficient synthesis of 2,6-functionalized pyranoid glycoaminoxy acid from commercially available methyl glucopyranoside is reported. The subsequent assembly of this glycoaminoxy acid building unit via N-acylation led successfully to the novel 2,6-linked oligosaccharide mimetics.",10.1055/s-0030-1260139,2011-07-28,0.5916650215562269
Journal of Organic Chemistry,Synthetic Studies on Stevastelins. 1. Total Synthesis of Stevastelins B and B3,"[Chemical reaction: See text] The synthesis of stevastelin B3 (2) and B (5) are described. In a first approach, epoxy cyclodepsipeptide 8 was considered as a promising candidate for the synthesis of the [15]-membered ring members of the stevastelins; however, the oxirane ring opening, required for the completion of the natural stevastelin synthesis, failed. Thus, we synthesized stevastelin B (5), carrying out the oxirane ring opening earlier in the synthesis and following a synthetic scheme capable of delivering analogues. On the other hand, a translactonization reaction of the [15]-membered ring derivative 59 led to the total synthesis of the natural [13]-membered ring component of the stevastelins family, stevastelin B3 (2).",10.1021/jo050625l,2005-08-30,0.5916648695338854
Synthesis,"A Palladium-Catalyzed Synthesis of Isoalliin, the Main Cysteine Sulfoxide in Onions <i>(Allium cepa)</i>","The natural sulfur compound isoalliin, (+)-(R)-3-[(E)-prop-1-enylsulfinyl]-2-aminopropanoic acid, was synthesized as a mixture of diastereomers in five steps from the hydrochloride of l-cysteine ethyl ester comprising an efficient - albeit unusual - Pd-catalyzed C-S coupling as the key step. Isoalliin is in demand in the field of Allium chemistry and serves as a standard for different determination methods in breeding research on Alliaceae, like onions, leek, or garlic.",10.1055/s-2006-950216,2006-10-01,0.5916536906785971
Organic Letters,Synthetic Study toward the Misassigned (±)-Tronoharine,"The synthesis of a pentacyclic indole compound corresponding to the core structure of the misassigned indole alkaloid, tronoharine (1), is presented. The key reactions were a formal [3 + 3] cycloaddition of an indol-2-yl carbinol with an azadiene for the construction of the 6/5/6/6 tetracyclic system containing an all-carbon quaternary center and an intramolecular substitution reaction of an amine and a triflate for the creation of the bridged azepine ring. In addition, some other interesting transformations discovered during the synthetic studies are also discussed.",10.1021/ol503734x,2015-01-20,0.591653075433422
Synlett,"Total Synthesis of Galtamycinone, the Common Aglycon of the C-Glycosyl Naphthacenequinone Antibiotics","All articles of this category Total synthesis of galtamycinone ( 1 ), the common structure in the C -glycosyl naphthacenequinone-class antibiotics, is described. The key step is the base-promoted regioselective cycloaddition of C -glycosyl chloronaphthoquinone 2 with homophthalic anhydride 6 . Total synthesis - Naphthacenequinone - Antibiotic - Aryl C -glycoside - Cycloaddition",10.1055/s-1996-5461,1996-05-01,0.5916488284061231
Organic Process Research & Development,A Practical and Efficient Synthesis of Thalidomide via Na/Liquid NH<sub>3</sub> Methodology<sup>1</sup>,"A facile, efficient, concise, cost-effective, and scalable synthesis of thalidomide in high overall yield (55%) is presented. Treatment of Boc-protected l -glutamic acid diester via Na/liquid (liq.) NH 3 (−33 °C) mediated cyclization methodology produces a corresponding glutarimide ring which was subsequently condensed with phthalic anhydride in the presence of glacial acetic acid to afford thalidomide.",10.1021/op050129z,2005-10-20,0.5916476397489521
Journal of Organic Chemistry,"Acid-Catalyzed Multicomponent Tandem Double Cyclization: A One-pot, Metal-free Route to Synthesize Polyfunctional 4,9-Dihydropyrrolo[2,1-<i>b</i>]quinazolines","An acid-catalyzed multicomponent tandem double cyclization protocol has been developed for the synthesis of polyfunctional 4,9-dihydropyrrolo[2,1-b]quinazolines from simple and readily available arylglyoxal monohydrates, 2-aminobenzylamine, and trans-β-nitrostyrenes. This practical and metal-free reaction proceeds through an imine formation/cyclization/Michael addition/Henry cyclization protocol, resulting in the construction of four new bonds and two ring moieties directly in one pot.",10.1021/acs.joc.6b01660,2016-08-09,0.5916474972506114
European Journal of Organic Chemistry,Facile Synthesis of Enantiomerically Pure Carbafuranoses: Precursors of Carbocyclic Nucleosides,"An efficient and highly diastereoselective synthetic approach to enantiomerically pure (−)-(1R,2R,3S,4R)- and (+)-(1S,2S,3R,4S)-4-hydroxyethylcyclopentane-1,2,3-triols is reported, which involves conversion of D-ribose or D-arabinose to (+)- or (−)-ethyl Z-4,5-isopropylidenedioxyhepta-2,6-dienoate, mercuration of the terminal double bond by mercury(II) acetate, followed by reductive radical cyclization and further standard reduction and deprotection manipulations.",10.1002/1099-0690(200101)2001:1<79::aid-ejoc79>3.3.co;2-t,2001-01-01,0.5916451919093179
European Journal of Organic Chemistry,Facile Synthesis of Enantiomerically Pure Carbafuranoses: Precursors of Carbocyclic Nucleosides,"An efficient and highly diastereoselective synthetic approach to enantiomerically pure (−)-(1R,2R,3S,4R)- and (+)-(1S,2S,3R,4S)-4-hydroxyethylcyclopentane-1,2,3-triols is reported, which involves conversion of D-ribose or D-arabinose to (+)- or (−)-ethyl Z-4,5-isopropylidenedioxyhepta-2,6-dienoate, mercuration of the terminal double bond by mercury(II) acetate, followed by reductive radical cyclization and further standard reduction and deprotection manipulations.",10.1002/1099-0690(200101)2001:1<79::aid-ejoc79>3.0.co;2-1,2001-01-01,0.5916451919093179
Tetrahedron,"Reaction of 5-aryloxazolidines with arylmagnesium bromides as a new route to N-benzyl-β-hydroxyphenethylamines as starting materials for the preparation of 4-aryl-1,2,3,4-tetrahydroisoquinolines",,10.1016/j.tetlet.2013.03.076,2013-03-23,0.591643412359291
Journal of Organic Chemistry,Carbocyclic Ribosylamines:  Synthesis of 5-Substituted Carbocyclic β-Ribofuranosylamines,"A synthesis of 5-substituted cyclopentylamine precursors for 5'-substituted carbocyclic nucleoside analogues was developed. We show that the stereochemistry of the OsO4-catalyzed hydroxylation of an apically brominated lactam, 7-bromo-2-azabicyclo[2.2.1]hept-5-en-3-one, can be controlled through the appropriate selection of the lactam N-H protecting group. Sterically large groups direct the hydroxylation to the exo-face of the olefin, yielding hydroxylation products that can be converted into analogues of carbocyclic ribosides. Conversely, a sterically small protecting group permits OsO4 approach from the endo-face, yielding hydroxylation products analogous to carbocyclic lyxosides. A key intermediate for carbocyclic sugar production, (1S,2S,3R, 4R,5S)-1-(tert-butyloxycarbonyl)amino-5-bromo-2,3-(dimethylmethylene)dioxy-4-hydroxymethylcyclopentane, was synthesized starting from a commercially available enantiomerically pure lactam, (1S)-(+)-2-azabicyclo[2.2.1]hept-5-en-3-one, in seven steps in an overall yield of 21%.",10.1021/jo060920l,2006-08-31,0.5916380618689107
Organic Letters,Asymmetric Total Synthesis and Formal Total Synthesis of the Antitumor Sesquiterpenoid (+)-Eremantholide A,"[structure: see text]. A new asymmetric total synthesis of (+)-eremantholide A is reported in which a Hoveyda-Grubbs ring-closing metathesis (RCM) reaction is used to assemble the nine-membered oxonin ring, and an enolate alkylation between the 3(2H)-furanone 2 and O-triflate 3 is exploited for C(9)-C(10) bond construction. An Evans asymmetric aldol reaction and a Sharpless asymmetric epoxidation served to stereoselectively install the C(6), C(7), and C(8) stereocenters of the target structure.",10.1021/ol0700862,2007-02-28,0.5916296903533177
Synlett,"An Efficient Approach to the Synthesis of 1,1-Diphenyl-1-silacycloheptan-4-one","All articles of this category 1,1-Diphenyl-1-sila-cycloheptan-4-one 1 is obtained through a straightforward three-step synthesis from commercially available divinyldiphenylsilane in 50% overall yield. Organosilicon compounds - 1,1-diphenyl-1-sila-cycloheptan-4-one - 1,1-diphenyl-1-sila-cyclohexan-4-one - hydroboration reaction",10.1055/s-1995-4847,1995-01-01,0.5916285821938885
Synthesis,"Expedient Synthesis of 1,3-Substituted Benzene Peptidomimetics","A synthetic route for replacing the central amino acid in the tripeptide Thr-Ala-Val (TAV) with a 1,3-substituted benzene ring was developed. l-Threonine was introduced into the benzene ring by a Grignard reaction with protected l-threoninal, where the nature of the side-chain protecting group was found to be of utmost importance. Subsequently, l-valine was introduced by a copper-mediated amination. Overall, the tripeptide analogue was obtained in six steps with an overall yield of 18%. An orthogonal protecting group strategy allowed attachment of the tripeptide analogue to a solid support and subsequent preparation of the corresponding pentapeptide analogue. Both compounds were tested in a plasma stability assay, showing improved stability compared to their peptide counterparts.",10.1055/s-0030-1258425,2011-02-08,0.5916223595827638
Journal of Organic Chemistry,Synthesis of Nonracemic 3-Deoxyschweinfurthin B,"Synthesis of nonracemic 3-deoxyschweinfurthin B has been accomplished through a synthetic sequence including a key cascade cyclization of an epoxy olefin. The intermediate epoxide could be prepared as a single enantiomer through an AD-mix-alpha (or AD-mix-beta) oxidation, and the stereochemistry of the epoxide has been shown to control formation of the two additional stereogenic centers created through the cyclization. Synthetic 3-deoxyschweinfurthin B was found to have potent differential activity in the National Cancer Institute's 60 cell line anticancer assay. This represents the first synthesis of the tetracyclic schweinfurthin skeleton, validating our overall synthetic strategy and providing the first schweinfurthin analogue with activity slightly greater than those of the natural products.",10.1021/jo048444r,2005-01-11,0.5916202486642828
European Journal of Organic Chemistry,Total Synthesis and Configurational Validation of (+)‐Violapyrone C,"Abstract Gold(I)‐catalyzed intramolecular 6‐ endo ‐ dig cyclization of tert ‐butyl ynoates afforded α‐pyrone cores of violapyrones. Moreover, this reaction was successfully applied to the stereospecific syntheses of (+)‐ and (–)‐violapyrone C, which allowed the absolute configuration of natural (+)‐violapyrone C to be assigned by comparison of the optical rotations. This first total synthesis, which proceeded in 22 % yield over 10 steps from ( S )‐(–)‐2‐methylbutanol, features silver(I) oxide promoted monobenzylation of 1,4‐butanediol, Wittig olefination, Claisen condensation, Corey–Fuchs reaction, and gold(I)‐catalyzed α‐pyrone synthesis.",10.1002/ejoc.201402524,2014-06-16,0.5916163234571037
Journal of Organic Chemistry,S<sub>N</sub>2 Reaction of Sulfur Nucleophiles with Hindered Sulfamidates:  Enantioselective Synthesis of α-Methylisocysteine,"The work described here demonstrates that the five-membered cyclic alpha-methylisoserine-derived sulfamidate, (R)-1, behaves as an excellent chiral building block for the ring-opening reaction by S(N)2 attack with sulfur nucleophiles at the quaternary carbon. As a synthetic application of this methodology, and to show that this sulfamidate is a valuable starting material, the synthesis of two new alpha-methylisocysteine derivatives has been carried out to cover the lack of alpha- and beta-methylated amino acids that incorporate the cysteine or isocysteine skeleton. These compounds are two new alpha,alpha-disubstituted beta-amino acids (beta(2,2)-amino acids), and the synthetic routes involve nucleophilic ring opening followed by acid hydrolysis.",10.1021/jo051632c,2006-01-13,0.5916138895115183
Angewandte Chemie International Edition,Cover Picture: Convergent Asymmetric Synthesis of (+)‐Aureothin Employing an Oxygenase‐Mediated Resolution Step (Angew. Chem. Int. Ed. 38/2012),"Maximized convergence is the key in the assembly of the carbon backbone of the densely functionalized natural product (+)-aureothin, as C. Hertweck and M. De Paolis et al. report in their Communication on page 9587 ff. The final step in the synthesis is the regiodivergent parallel kinetic resolution of the racemic precursor through in vivo treatment with a cytochrome P450 monooxygenase. (Background photography courtesy of Nico Überschaar; the authors also thank Martin E. A. Richter and Jonathan Rangapanaiken for their contribution to the cover picture.)",10.1002/anie.201206228,2012-08-15,0.5916135459207387
Tetrahedron,Diamondoid rearrangements in chlorosulphonic acid. A highly regioselective route to apically disubstituted diamantanes,,10.1016/s0040-4039(00)72480-4,1975-01-01,0.5916110750560065
Organic Letters,Diastereo- and Enantioselective Copper-Catalyzed Intramolecular Carboamination of Alkenes for the Synthesis of Hexahydro-1<i>H</i>-benz[<i>f</i>]indoles,A new method for the enantioselective synthesis of hexahydro-1H-benz[f]indoles is described. This copper-catalyzed enantioselective intramolecular alkene carboamination process can install vicinal tertiary and quaternary carbon stereocenters with high levels of diastereo- and enantioselectivity. The C-C bond-forming component of the reaction constitutes a C-H functionalization and no electronic activation of the aryl ring that undergoes addition is required. A known 5-HT(1A) receptor antagonist was synthesized efficiently using this method.,10.1021/ol102233g,2010-09-28,0.5916102889157117
Synthesis,The Carbohydrate-Sesquiterpene Interface. A Zirconocene-Mediated Synthesis of (+)-Epiafricanol from <scp>d</scp>-Glucose,"A total synthesis of (+)-epiafricanol (6) has been readily achieved from d-glucose. The tricyclic alcohol target was arrived at by first forming methyl 6-O-benzyl-2-deoxy-2-C-methyl-α-d-altropyranoside (12) and converting this intermediate into methyl 2-C-methyl-2,3,4-trideoxy-α-d-threo-hexopyranoside (14). There followed a series of steps resulting in extension of the side chain to give the isopropenyl pyranoside 9. This advanced intermediate was subjected to zirconocene-promoted ring contraction, which gave rise to 8 and set the stage for conversion to 7. This tertiary carbinol was transformed into 6 by sequential ring-closing metathesis and stereodirected Simmons-Smith cyclopropanation.",10.1055/s-2002-34380,2002-09-26,0.5916099197617811
Organic Letters,Total Synthesis of Tunicamycin V,"The total synthesis of tunicamycin V is described. This strategy is based on the initial construction of tunicaminyluracil, which is regarded to play an important role in the observed biological activities. The key to the synthesis was a Mukaiyama aldol reaction followed by a furan-oxidation to construct the undecose skeleton, a [3,3] sigmatropic rearrangement of a cyanate, and a highly selective trehalose-type glycosylation.",10.1021/acs.orglett.7b03623,2017-12-19,0.5916093439998306
Tetrahedron,Convenient synthesis of N-(4-(2-aminopyridin-4-yl)thiazol-2-yl)-2-phenylacetamides,,10.1016/j.tetlet.2006.09.053,2006-10-05,0.5916075853203756
Tetrahedron,"(S, S)-diisopropylethanediol (“DIPED”): A new chiral director for the α-chloro boronic ester synthesis",,10.1016/s0040-4039(00)83891-5,1986-01-01,0.591600036391488
Angewandte Chemie International Edition,Development of an Alkaloid–Pyrone Annulation: Synthesis of Pleiomaltinine,Odd Couple: A method for the synthesis of alkaloid-pyrones using a novel pyrone annulation of β-carbolines and indoles with 3-siloxy-4-pyrones is reported. The approach has enabled synthesis of the unusual alkaloid-pyrone pleiomaltinine from the plant-derived indole-alkaloid pleiocarpamine (see Scheme; TBS= tert-butyldimethylsilyl).,10.1002/anie.201204093,2012-08-15,0.5915997480648977
Organic Letters,Total Synthesis of the Repeating Units of <i>O</i>-Specific Polysaccharide of <i>Pseudomonas chlororaphis</i> subsp. <i>aureofaciens</i> UCM B-306 via One-Pot Glycosylation,"Herein we report the first total syntheses of the trisaccharide-repeating units of Pseudomonas chlororaphis subsp. aureofaciens UCM B-306 via a one-pot assembly of the core trisaccharide structure. The rare-sugar-containing trisaccharide-repeating units are comprised of d -bacillosamine, 2-amino-2-deoxy- d -galacturonic acid or amide, and d -rhamnose units linked through three consecutive α-linkages. The total syntheses of two repeating units were completed starting from d -mannose via a longest-linear sequence of 27 steps in 5.8% and 4.4% overall yields, respectively.",10.1021/acs.orglett.2c01318,2022-05-13,0.5915934210388767
Tetrahedron,Total synthesis of the macrolide (+)-aspicilin by an asymmetrically catalyzed macrocyclization of an ω-Alkynal ester,,10.1016/0040-4039(95)00351-c,1995-04-01,0.5915852953075122
Synlett,"Proline-Catalyzed α-Aminooxylation of β-Amino Aldehydes: Access to Enantiomerically Pure syn- and anti-3-Amino-3-aryl-1,2-alkanediols","A new synthetic method for enantioselective synthesis of syn or anti -3-amino-3-aryl-1,2-alkanediols via proline catalyzed α-aminooxylation of β-amino aldehydes are described. This methodology is successfully applied to a concise and protecting group-free asymmetric synthesis of (–)-cytoxazone, (+)- epi -cytoxazone and formal synthesis of N-thiolated 2-oxazolidinone.",10.1055/s-0034-1379735,2015-01-09,0.5915777022796647
Angewandte Chemie International Edition,Asymmetric Total Synthesis of Fredericamycin A,"Seventeen years after the isolation of the promising antitumor antibiotic fredericamycin A, the first asymmetric total synthesis of this compound has been accomplished and thereby its absolute configuration established. The key feature is the regiocontrolled [4+2] cycloaddition of 3 to 2, which was obtained by the stereospecific rearrangement of 1. Cp = (-)-camphanoyl.",10.1002/(sici)1521-3773(19990301)38:5<683::aid-anie683>3.0.co;2-0,1999-03-01,0.5915683627143843
Angewandte Chemie International Edition,Asymmetric Total Synthesis of Fredericamycin A,"Seventeen years after the isolation of the promising antitumor antibiotic fredericamycin A, the first asymmetric total synthesis of this compound has been accomplished and thereby its absolute configuration established. The key feature is the regiocontrolled [4+2] cycloaddition of 3 to 2, which was obtained by the stereospecific rearrangement of 1. Cp = (−)-camphanoyl.",10.1002/(sici)1521-3773(19990301)38:5<683::aid-anie683>3.3.co;2-s,1999-03-01,0.5915683627143843
Tetrahedron,β-Fragmentation of alkoxy radicals. An approach to the synthesis of ring a of vernolepin,,10.1016/s0040-4039(00)95523-0,1987-01-01,0.591567558428073
Tetrahedron,Synthesis of CC biaryl segment of complestatin and chloropeptin: Approach to the right hand CEF-ring system of complestatin,,10.1016/s0040-4039(97)00272-4,1997-03-01,0.591567558428073
Angewandte Chemie International Edition,Total Synthesis of (+)‐Asperolide C by Iridium‐Catalyzed Enantioselective Polyene Cyclization,"Domino rings: A general synthetic entry into labdane-type diterpenoids has been developed based on an iridium-catalyzed enantioselective polyene cyclization cascade. The potential of this process is demonstrated in the first total synthesis of the tetranorlabdane diterpene asperolide C (PMB=p-methoxybenzyl, TMS= trimethylsilyl).",10.1002/anie.201307187,2013-09-24,0.5915592449405069
Journal of Organic Chemistry,A General Approach to 3-<i>n</i>-Butyl-5-alkylindolizidines:  Total Synthesis of (−)-Indolizidine 195B,"Indolizidine type alkaloids have been attractive synthetic targets due to their biological activity. The total synthesis of (-)-indolizidine 195B via a general route, which could potentially be used to prepare other indolizidine alkaloids such as (-)-gephyrotoxin 223AB and (-)-myrmicarin 237A, is described.",10.1021/jo7015423,2007-10-19,0.5915550846324709
Organic Process Research & Development,"Development of a Safe and Efficient Two-Step Synthesis for Preparing 1-Bromoacetyl-3,3-dinitroazetidine, a Novel Clinical Anticancer Candidate","An efficient process for synthesizing and isolating a new investigative anticancer agent, 1-bromoacetyl-3,3-dinitroazetidine, is described. The reaction entails a sequence of oxidative nitration followed by acylative dealkylation. The methods reported give 50–60-g batches of high-purity product without a designated purification step. The reaction conditions have been designed to mitigate the safety concerns associated with gem -dinitroazetidines. Some observations on the acylative dealkylation mechanism are discussed.",10.1021/op2003216,2012-02-15,0.5915548830291117
Journal of Organic Chemistry,"Metal-Catalyzed Domino Synthesis of Benzophenanthridines and 6<i>H</i>-Naphtho[2,3-<i>c</i>]-chromenes","A new and efficient synthesis of tetracyclic phenanthridines and benzo[ c]chromenes has been described involving a metal-mediated two-step domino strategy. The first step involved efficient palladium-catalyzed domino carbopalladation/cross coupling, and the second step involved iron-catalyzed domino isomerization/cyclodehydration. The important features of this strategy include high yields, generality, wide substrate scope, and broad functional group tolerance. A plausible mechanism has been proposed to explain the formation of the product.",10.1021/acs.joc.8b00924,2018-06-11,0.5915540808920622
Journal of Organic Chemistry,A Novel Route to the Marasmane Skeleton via a Tandem Rearrangement−Cyclopropanation Reaction. Total Synthesis of (+)-Isovelleral,A general and efficient route to the marasmane skeleton is described. Total syntheses of two simple marasmanes (35 and 37) in racemic form were achieved using a MgI2-catalyzed rearrangement-cyclopropanation reaction of trimethylsilyl enol ether 31 derived from naphthalenone 30. The reaction proceeds in high yield with complete diastereoselectivity and does not require the use of special cyclopropanation reagents. Application of this novel route to the marasmane framework was extended to the synthesis of naturally occurring (+)-isovelleral (41).,10.1021/jo0015568,2001-03-08,0.5915493128276308
Synlett,Process Research and Development for Heterocyclic p38 MAP Kinase Inhibitors,"The need to access different heterocyclic cores as part of p38 MAP kinase inhibitors led to the discovery and development of several efficient approaches to three separate classes of heterocycles, namely phthalazines, pyrazolopyridinones, and triazolopyridines. This account summarizes our studies in this field in a comprehensive fashion. 1 Introduction 2 Synthesis of Phthalazine-Based p38 Inhibitors 2.1 Synthesis of Clinical Candidate 2 2.2 Synthesis of Clinical Candidate 3 3 Synthesis of Pyrazolopyridinone-Based p38 Inhibitors 4 Synthesis of Triazolopyridine-Based p38 Inhibitors 4.1 Synthesis through Pd-Catalyzed Benzhydrazide Couplings 4.2 Synthesis through Pd-Catalyzed Benzhydrazone Couplings 5.0 Conclusions",10.1055/s-0031-1290425,2012-06-11,0.5915486551880369
Tetrahedron,Efficient synthesis of substituted piperazinones via tandem reductive amination–cyclization,,10.1016/s0040-4039(00)01063-7,2000-08-01,0.5915459189037355
Synthesis,Stereoselective Synthesis of a Key Intermediate of (-)-Apicularen A,"Progress towards the stereoselective formal synthesis of (-)-apicularen A is described. The convergent approach involves the assembly of aliphatic and aromatic fragments via Grubbs’s cross metathesis. Other key reactions in the strategy include Sharpless asymmetric epoxidation, Evans’s protocol for the generation of syn 1,3-diol systems and stereoselective reduction.",10.1055/s-2007-965979,2007-04-01,0.5915429951392392
Tetrahedron,Synthesis of a chiral hexa-host molecule,,10.1016/s0040-4039(00)71414-6,1980-01-01,0.5915394814310238
Organic Letters,Enantioselective and Diastereoselective Construction of Chiral Amino Alcohols by Iridium–f-Amphox-Catalyzed Asymmetric Hydrogenation via Dynamic Kinetic Resolution,"The iridium-f-amphox-catalyzed asymmetric hydrogenation of racemic α-amino β-unfunctionalized ketones proceeds via a DKR (dynamic kinetic resolution) process for the construction of various chiral N,N-disubstituted α-amino β-unfunctionalized alcohols in quantitative yields with excellent enantioselectivities and diastereoselectivities (all products >99% ee and >99:1 dr, TON up to 100 000). Importantly, this catalytic asymmetric hydrogenation with a DKR process provided a highly efficient and powerful synthetic strategy for the preparation of key chiral intermediates of the preclinical antitumor agent (S,S)-R116010.",10.1021/acs.orglett.7b00844,2017-04-27,0.5915391852000853
Organic Letters,Synthesis of<i>tert</i>-Butyl 6-Oxo-2-azaspiro[3.3]heptane-2-carboxylate,Two efficient and scaleable synthetic routes to previously unknown bifunctional tert-butyl 6-oxo-2-azaspiro[3.3]heptane-2-carboxylate are described. This compound and related intermediates described herein are useful for further selective derivation on the azetidine and cyclobutane rings providing a convenient entry point to novel compounds accessing chemical space complementary to piperidine ring systems.,10.1021/ol901325s,2009-07-28,0.5915364635600228
Chemical Science,Divergent enantioselective synthesis of hapalindole-type alkaloids using catalytic asymmetric hydrogenation of a ketone to construct the chiral core structure,A divergent enantioselective approach to hapalindole-type alkaloids featuring a ruthenium-catalyzed asymmetric hydrogenation and a switchable sequence of methylation and acetylation/aldol reaction is described.,10.1039/c6sc00686h,2016-01-01,0.5915326652016387
Journal of Organic Chemistry,Synthetic Studies toward <i>Mycobacterium tuberculosis</i> Sulfolipid-I,"Sulfolipid-I (SL-I) is an abundant metabolite found in the cell wall of Mycobacterium tuberculosis that is comprised of a trehalose 2-sulfate core modified with four fatty acyl substituents. The correlation of its abundance with the virulence of clinical isolates suggests a role for SL-I in pathogenesis, although its biological functions remain unknown. Here we describe the synthesis of a SL-I analogue bearing unnatural lipid substituents. A key feature of the synthesis was application of an intramolecular aglycon delivery reaction to join two differentially protected glucose monomers, one prepared with a novel alpha-selective glycosylation. The route developed for the model compound can be readily extended to the synthesis of native SL-I as well as additional analogues for use in the investigation of SL-I's functions.",10.1021/jo702032c,2008-01-04,0.5915281623165065
Organic Letters,Synthesis of Cyclic Hemiketals and Spiroketals from Dioxanorbornanes,[reaction: see text] A new method for the synthesis of substituted pyranone hemiketals from dioxanorbornanes via SmI(2) is described. Also reported is a synthesis of spiro[4.5]ketals from analogous intermediates via acid-promoted deprotection/ketalization.,10.1021/ol048578r,2004-09-22,0.5915193788182347
Organic Letters,"A New Glycociamidine Ring Precursor:  Syntheses of (<i>Z</i>)-Hymenialdisine, (<i>Z</i>)-2-Debromohymenialdisine, and (±)-<i>endo</i>-2-Debromohymenialdisine","[chemical reaction: see text]. The synthesis of the C11H5 marine sponge alkaloids, (Z)-hymenialdisine and (Z)-2-debromohymenialdisine, is described. A key step was the condensation between aldisine or its monobromo derivative and a new, efficient imidazolinone-based glycociamidine precursor. In the first case, the main product turned out to be the unprecedented (+/-)-endo-2-debromohymenialdisine.",10.1021/ol052266m,2005-11-15,0.5915167405158448
Synlett,"Regioselective N-Acylation of 3-Arylmethylpiperazine-2,5-diones: Short Synthesis of (-)-Glyantrypine and (-)-Fumiquinazoline F","All articles of this category The folded conformation of the 3-arylmethyl substituent in 2,5-bis -O -trimethylsilyl-3,6-dihydropyrazines derived from the corresponding piperazine-2,5-diones, shields the N (1)-position allowing monoacylation at the neighbouring nitrogen atom. This regioselectivity was used to develop a four-step total synthesis of (-)-glyantrypine and (-)-fumiquinazoline F starting from d-tryptophan methyl ester. regioselectivity - acylation - Wittig reactions - asymmetric synthesis - total synthesis",10.1055/s-2001-16785,2001-01-01,0.59150500763413
Synthesis,Dehydrogenative Heck Annelations of Internal Alkynes,"This review covers the palladium-catalyzed annelations of internal alkynes through reactions leading to the loss of only two hydrogens from the substrates. They occur via (i) dual C–H bond activation, (ii) both C–H and N–H bond activation, (iii) successive amino(or oxy)palladation and C–H bond activation, or (iv) C–H bond activation followed by a Heck-type process. The proposed mechanisms are described with, in some cases, personal commentary. 1 Introduction 2 Synthesis of Aryl Rings 2.1 Via Aryl–Alkyne Coupling 2.2 Via Allylaryl–Alkyne Coupling 2.3 Via Cyclopentadienyl–Alkyne Coupling 2.4 Via Benzoylacetate–Alkyne Coupling 2.5 Via Indole–Alkyne Coupling 2.6 Via Benzothiophene–Alkyne or Benzofuran–Alkyne Coupling 3 Synthesis of Pyrrole Rings 3.1 Via Imidazo[1,2- a ]pyridine–Alkyne Coupling 3.2 Via Aniline–Alkyne Coupling 3.3 Via Enamine–Alkyne Coupling 3.4 Via Enamide–Alkyne Coupling 3.5 Via Indole–Alkyne Coupling and Rearrangement 4 Synthesis of Pyridinone Rings 4.1 Via Indole-carboxamide–Alkyne Coupling 4.2 Via Arylcarboxamide–Alkyne Coupling 5 Synthesis of Furan Rings 6 Synthesis of Azepine Rings 7 Synthesis of Spiroindenes 8 Synthesis of Cyclopentadiene Rings 8.1 Via Arylalkyne Self-Coupling 8.2 Via Alkenylindole–Alkyne Coupling 9 Conclusion",10.1055/s-0033-1338631,2014-05-05,0.591502055530398
European Journal of Organic Chemistry,Approaches to Styrenyl Building Blocks for the Synthesis of Polyene Xanthomonadin and its Analogues,"A number of aryl building blocks for the synthesis of two xanthomonadin natural product pigments, as well as a related analogue, were accessed using a divergent hydroboration/bromoboration approach from a key alkynyl intermediate. A new approach towards substitution patterns around the ring was adopted following the isolation of an unexpected regioisomer from the bromination reaction. Potential coupling reactions onto these building blocks were explored, with a successful Sonogashira coupling performed on the key alkynyl intermediate, and with the key debrominated styrenyl boronate ester intermediate functionalised both by preliminary Suzuki–Miyaura coupling and by iododeboronation/Heck–Mizoroki coupling. Coupling reactions with brominated styrenyl intermediates proved much more challenging due to the instability of the intermediates to cross‐coupling, but some studies have shown promise.",10.1002/ejoc.201800540,2018-09-13,0.5914971346994601
Journal of Organic Chemistry,Asymmetric Synthesis of a Bacteriochlorophyll Model Compound Containing <i>trans</i>-Dialkyl Substituents in Ring D,"Challenges to the de novo synthesis of bacteriochlorophyll a ( BChl a ), the chief pigment for anoxygenic bacterial photosynthesis, include creating the macrocycle along with the trans -dialkyl substituents in both pyrroline rings (B and D). A known route to a model bacteriochlorophyll with a gem-dimethyl group in each pyrroline ring has been probed for utility in the synthesis of BChl a by preparation of a hybrid macrocycle ( BC-1 ), which contains a trans -dialkyl group in ring D and a gem-dimethyl group in ring B. Stereochemical definition began with the synthesis of (2 S,3 S )-2-ethyl-3-methylpent-4-ynoic acid, a precursor to the trans -dialkyl-substituted AD dihydrodipyrrin. Knoevenagel condensation of the latter and a gem-dimethyl, β-ketoester-substituted BC dihydrodipyrrin afforded the enone (E, 70%; Z, 3%); subsequent double-ring cyclization of the E -enone (via Nazarov, electrophilic aromatic substitution, and elimination reactions) gave BC-1 (53% yield) along with a trace of chlorin byproduct (1.4% relative to BC-1 upon fluorescence assay). BC-1 exhibited the desired trans -dialkyl stereochemistry in ring D and was obtained as a 7:1 mixture of (expected) epimers owing to the configuration of the 13 2 -carbomethoxy substituent. The strategy wherein trans -dialkyl substituents are installed very early and carried through to completion, as validated herein, potentially opens a synthetic path to native photosynthetic pigments.",10.1021/acs.joc.0c00608,2020-05-04,0.5914949557676248
Tetrahedron,"Proline catalyzed enantioselective synthesis of (2 S ,3 S )-3-hydroxypipecolic acid and formal synthesis of (+)-swainsonine",,10.1016/j.tetlet.2016.03.042,2016-03-15,0.591487563331136
Journal of Organic Chemistry,"General Approach for the Synthesis of 12-Methoxy-Substituted Sarpagine Indole Alkaloids Including (−)-12-Methoxy-<i>N</i><sub>b</sub>-methylvoachalotine, (+)-12-Methoxy-<i>N</i><sub>a</sub>-methylvellosimine, (+)-12-Methoxyaffinisine, and (−)-Fuchsiaefoline","[structures: see text] The enantiospecific synthesis of 7-methoxy-D-tryptophan ethyl ester was completed by combination of the Larock heteroannulation process with a Schöllkopf-based chiral auxiliary in good yield. This ester was then employed in the first regiospecific, stereospecific total synthesis of (+)-12-methoxy-N(a)-methylvellosimine, (+)-12-methoxyaffinisine, (-)-fuchsiaefoline, and 12-methoxy-N(b)-methylvoachalotine in excellent overall yield. The asymmetric Pictet-Spengler reaction and enolate-driven palladium-catalyzed cross-coupling processes served as key steps. The quaternary center at C16 of 12-methoxy-N(b)-methylvoachalotine was established via the Tollens reaction between (+)-12-methoxy-N(a)-methylvellosimine and formaldehyde to form diol 17. The two prochiral primary alcohols in diol 17 were differentiated by the oxidative cyclization(DDQ) of the hydroxyl group at the axial position of 17 with the benzylic postion at [C6] to form a cyclic ether [C6-O17]. After oxidative formation of the alpha-ester at C16, the ether bond was reductively cleaved with TFA/Et3SiH in high yield. The DDQ-mediated oxidative cyclization and TFA/Et3SiH reductive cleavage served as protection/deprotection steps in order to provide a versatile entry into the voachalotine alkaloids.",10.1021/jo052081t,2005-12-08,0.5914875234278039
Journal of Organic Chemistry,"Conformationally Constrained Dipeptide Surrogates with Aromatic Side-Chains:  Synthesis of 4-Aryl Indolizidin-9-one Amino Acids by Conjugate Addition to a Common α,ω-Diaminoazelate Enone Intermediate","Four methyl 9-oxo-8-(N-(Boc)-amino)-4-phenyl-1-azabicyclo[4.3.0]nonane carboxylates (11, 4-Ph-I(9)aa-OMe) were synthesized from (2S,8S,5E)-di-tert-butyl-4-oxo-5-ene-2,8-bis[N-(PhF)amino]azelate [(5E)-7, PhF = 9-(9-phenylfluorenyl)] via a seven-step process featuring a conjugate addition/reductive amination/lactam cyclization sequence. Various nucleophiles were used in the conjugate addition reactions on enone (5E)-7 as a general route for making alpha,omega-diaminoazelates possessing different substituents in good yield albeit low diastereoselectivity except in the case of aryl Grignard reagents (9/1 to 15/1 drs). 6-Phenylazelates (6S)-8d and (6R)-8d were separated by chromatography and diastereoselective precipitation and independently transformed into 4-Ph-I(9)aa-OMe. From (6S)-8d, (2S,4R,6R,8S)-4-Ph-I(9)aa-OMe 11 was prepared selectively in 51% yield. Reductive amination of (6R)-8d provided the desired pipecolates 9 along with desamino compound 10, which was minimized by performing the hydrogenation in the presence of ammonium acetate. Subsequent ester exchange, lactam cyclization, and amine protection provided three products (2R,4S,6S,8R)-, (2R,4S,6S,8S)-, and (2S,4S,6R,8S)-4-Ph-I(9)aa-OMe 11 in 10, 6, and 6% yields, respectively, from (6R)-8d. Ester hydrolysis of (2S,4R,6R,8S)-11 furnished 4-phenyl indolizidin-9-one N-(Boc)amino acid 3 as a novel constrained Ala-Phe dipeptide surrogate for studying conformation-activity relationships of biologically active peptides.",10.1021/jo0355855,2004-02-11,0.5914851947239148
Journal of Organic Chemistry,Sustainable Synthesis of a Potent and Selective 5-HT <sub>7</sub> Receptor Antagonist Using a Mechanochemical Approach,"High Resolution Image Download MS PowerPoint Slide A mechanochemical procedure was developed to obtain PZ-1361, a potent and selective 5-HT 7 receptor antagonist, with antidepressant properties in rodents. The elaborated protocol offered several advantages over classical batch synthesis, including improvement of the overall yield (from 34% to 64%), reduction of reaction time (from 60 to 5.5 h), limitation of the use of toxic solvents, and the formation of byproducts. This approach represents a rare example of the synthesis of biologically active compounds exclusively performed using mechanochemical reactions.",10.1021/acs.joc.0c01044,2020-07-24,0.5914842665399581
Organic Process Research & Development,Large-Scale Synthesis of the Anti-Cancer Marine Natural Product (+)-Discodermolide. Part 3:  Synthesis of Fragment C<sub>15</sub><sub>-</sub><sub>21</sub>,Smith's procedure of preparing fragment C 15 - 21 ( 5 ) from common precursor 3 was optimized. The ease of plant operations made this six-step route successful for the production of several kilograms of this fragment with high purity.,10.1021/op034132z,2003-12-04,0.5914837567455579
Journal of Organic Chemistry,Stereoselective Synthesis of Annular 9-<i>cis</i>-Retinoids and Binding Characterization to the Retinoid X Receptor,"Analogues of 9-cis-retinoic acid incorporating an alicyclic ring between the C19 and C10 positions have been synthesized and evaluated as ligands for the RXRalpha nuclear receptor. The stereocontrolled synthesis of these configurationally constrained retinoids combines a Stille cross-coupling and the Wittig reaction as key bond-forming steps. The palladium-catalyzed cross-coupling reaction of the beta-bromo-alpha,beta-unsaturated aldehydes 5 to dienylstannane 6 is very fast at room temperature, and takes place with preservation of the dienylstannane geometry. A highly stereoselective Wittig reaction afforded the C7-C8 bond connecting the hydrophobic ring to the retinoid side chain. The binding affinities of these compounds for the receptor were determined, and the structural and energetic rationale behind the affinity profile of the cyclic 9-cis-retinoic acid derivatives for the RXRalpha nuclear receptor was characterized by using Molecular Mechanics protocols.",10.1021/jo0257391,2002-07-09,0.5914787702555416
Journal of Organic Chemistry,Divergent Synthesis of Porous Tetraphenylmethane Dendrimers,"Tetraphenylmethane-ethynylene-based shape-persistent dendrimers are a new class of nanoobjects with an intriguing 3D architecture. We report an efficient divergent strategy for their synthesis based on the Sonogashira Pd-catalyzed coupling of terminal alkynes with aryl iodides. As repeat unit, we prepared a tetraphenylmethane derivative bearing a terminal alkyne and three triazene moieties. Coupling of this building block to tetrakis(p-iodophenyl)methane afforded, after triazene activation, a dodecaiodo-terminated first generation dendrimer, which was transformed by another Sonogashira coupling into a methoxy-terminated second generation dendrimer with persistent globular shape and well-defined cavities. This work also unveils new aspects of triazene chemistry, i.e., the unprecedented efficient generation of an azo compound by mixing of a triazene with phenol.",10.1021/acs.joc.7b02302,2017-11-14,0.5914699455276196
Synthesis,A Quick and Efficient Route to 2-Substituted Cyclopentanones and Cyclohexanones,Preparation des composes du titre par alkylation puis decarboxylation des oxo-2 cyclopentane ou cyclohexane carboxylates de t-butyle,10.1055/s-1983-30597,1983-01-01,0.5914676398570105
Journal of the American Chemical Society,A Catalytic Approach for Enantioselective Synthesis of Homoallylic Alcohols Bearing a <i>Z</i>-Alkenyl Chloride or Trifluoromethyl Group. A Concise and Protecting Group-Free Synthesis of Mycothiazole,"A protecting group-free strategy is presented for diastereo- and enantioselective routes that can be used to prepare a wide variety of Z -homoallylic alcohols with significantly higher efficiency than is otherwise feasible. The approach entails the merger of several catalytic processes and is expected to facilitate the preparation of bioactive organic molecules. More specifically, Z- chloro-substituted allylic pinacolatoboronate is first obtained through stereoretentive cross-metathesis between Z -crotyl-B(pin) (pin = pinacolato) and Z -dichloroethene, both of which are commercially available. The organoboron compound may be used in the central transformation of the entire approach, an α- and enantioselective addition to an aldehyde, catalyzed by a proton-activated, chiral aminophenol-boryl catalyst. Catalytic cross-coupling can then furnish the desired Z -homoallylic alcohol in high enantiomeric purity. The olefin metathesis step can be carried out with substrates and a Mo-based complex that can be purchased. The aminophenol compound that is needed for the second catalytic step can be prepared in multigram quantities from inexpensive starting materials. A significant assortment of homoallylic alcohols bearing a Z -F 3 C-substituted alkene can also be prepared with similar high efficiency and regio-, diastereo-, and enantioselectivity. What is more, trisubstituted Z -alkenyl chloride moiety can be accessed with similar efficiency albeit with somewhat lower α-selectivity and enantioselectivity. The general utility of the approach is underscored by a succinct, protecting group-free, and enantioselective total synthesis of mycothiazole, a naturally occurring anticancer agent through a sequence that contains a longest linear sequence of nine steps (12 steps total), seven of which are catalytic, generating mycothiazole in 14.5% overall yield.",10.1021/jacs.9b11178,2019-12-24,0.5914637430867752
Organic Letters,"Construction of the [6,5,7,5] Tetracyclic Core of Calyciphylline A Type Alkaloids via a Tandem Semipinacol Rearrangement/Nicholas Reaction","A novel and efficient approach toward the assembly of the synthetically challenging tetracyclic [6,5,7,5] core structure of calyciphylline A-type alkaloids is developed. The synthetic route features a tandem semipinacol rearrangement/Nicholas reaction that has been devised strategically to construct the spirocyclic A/B ring and the sterically congested vicinal all-carbon quaternary carbon centers in high diastereoselectivity. Late-stage installation of the hydropyrrole ring and the strained 7-membered ring via a double-reductive amination and ring-closing metathesis, respectively, has also been realized.",10.1021/acs.orglett.7b02274,2017-08-24,0.5914601168180026
Journal of Organic Chemistry,"Improved Synthesis of Isogranulatimide, a G2 Checkpoint Inhibitor. Syntheses of Didemnimide C, Isodidemnimide A, Neodidemnimide A, 17-Methylgranulatimide, and Isogranulatimides A−C","A concise, improved synthesis of isogranulatimide (6), a naturally occurring substance with G2 checkpoint inhibition activity, is described. Also reported are the syntheses of didemnimide C (18), isodidemnimide A (24), neodidemnimide A (36), 17-methylgranulatimide (9), and isogranulatimides A (10), B (11), and C (12). Compounds 9-12, congeners of isogranulatimide (6), are now available for biological evaluation.",10.1021/jo9914723,1999-12-29,0.5914598117332124
Tetrahedron,Novel synthesis of indolylquinoline derivatives via the C-alkylation of Baylis–Hillman adducts,,10.1016/j.tetlet.2009.04.064,2009-04-23,0.5914596664019294
Organic Letters,Carboxybenzyl Group as an <i>O</i>-Nucleophile in the C–H Allylic Oxidation: Total Synthesis of (−)-Castanospermine,"The first palladium-mediated C-H allylic oxidation with a Cbz group acting as an O-nucleophile is reported. It was found that this transformation is promoted by rare-earth metal triflates: Yb(OTf)(3) or Sc(OTf)(3). A possible catalytic cycle is proposed. This reaction was applied in the synthesis of a d-xylose derived oxazolidinon, a versatile intermediate used further in the stereoselective synthesis of unnatural (-)-castanospermine. Cyclization of the key intermediate with PhSeBr afforded the desired bicyclic scaffold. In an alternative route, hydroboration/oxidation followed by DPPA-mediated cyclization was used.",10.1021/ol501730p,2014-07-08,0.5914570675627808
Tetrahedron,Asymmetric michael addition of a chiral ester-dienolate: enantioselective synthesis of (−)-khusimone,,10.1016/s0040-4039(01)99825-9,1983-01-01,0.5914560570426961
Organic Letters,Synthesis of Tanshinone IIA and Related Terpenes via a C–H Functionalization Strategy,"The total synthesis of tanshinone IIA and related bioactive diterpenes isolated from the Chinese plant Salvia miltiorrhiza was completed from a common tetralin building block. The synthetic route highlights a 3,4-disubstituted furan synthesis and various regioselective C–H functionalization reactions, including a Pd catalyzed iodination and an Ir catalyzed borylation, along with an intramolecular stanna-Brook type reaction to construct the ortho -quninone ring of the target molecule.",10.1021/acs.orglett.4c02438,2024-08-19,0.5914527473416523
Tetrahedron,New kilogram-synthesis of the anti-alzheimer drug (−)-galanthamine,,10.1016/s0040-4039(98)00294-9,1998-04-01,0.5914423946634164
Tetrahedron,A novel synthesis of guanine PDE inhibitors via tricyclic imidazopyrimidines,,10.1016/s0040-4039(03)00383-6,2003-03-01,0.5914390784273308
Tetrahedron,Silenes as novel synthetic reagents: synthesis of diols and lactones from simple alkyldienes,,10.1016/j.tetlet.2003.10.056,2003-11-24,0.5914378198931957
Synthesis,"Large-Scale Preparation of Pure (+)-(1<i>S</i>,2<i>R</i>,5<i>S</i>)-5-Methyl-2-(1-methyl-1-phenylethyl)cyclohexanol","All articles of this category A procedure is described for the preparation of ( S )-(-)-pulegone, (-)- 1 , starting from ( S )-(-)-citronellol, (-)- 6 , in a preparative scale. Compound (-)- 1 can easily be converted into (+)-(1 S ,2 R ,5 S )-5-methyl-2-(1-methyl-1-phenylethyl) cyclohexanol: (+)- 2 [""(+)-8-phenylmenthol""] by a procedure described in literature, which was simplified essentially. Now (+)- 2 is accessible in larger amounts and thus is available as an efficient chiral auxiliary in stoichiometric asymmetric syntheses.",10.1055/s-1988-27724,1988-01-01,0.591436468360776
Organic Process Research & Development,A New Industrial Process for 10-Methoxyiminostilbene: Key Intermediate for the Synthesis of Oxcarbazepine,"A new industrial process, involving only two isolation and drying steps, for 10-methoxyiminostilbene (MISB), an advance intermediate of widely prescribed antiepileptic drug, oxcarbazepine, has been developed. A salient feature of this process is the novel use of 1,3-dibromo-5,5-dimethylhydantoin (DBDMH) to afford bromohydrin methyl ether from N -acetyliminostilbene. The byproducts of this process namely acetic acid, 5,5-dimethylhydantoin and Et 3 N·HBr are recyclable as well as nontoxic. This process is amenable for the large-scale production of MISB.",10.1021/op900127v,2009-08-20,0.5914264421894265
European Journal of Organic Chemistry,"A Flexible Approach to 6,5‐Benzannulated Spiroketals","Abstract A novel route to simple 6,5‐benzannulated spiroketal analogues has been developed. A convergent Horner–Wadsworth–Emmons olefination enabled ready assembly of the spiroketal precursors. Use of a benzyl protecting group strategy enabled an efficient one‐pot hydrogenation/deprotection/spiroketalisation process to be employed providing a robust method to access a range of substituted aromatic monobenzannulated spiroketals.",10.1002/ejoc.201100345,2011-05-18,0.5914219840148164
European Journal of Organic Chemistry,Synthesis of Oxa‐B‐Ring Analogs of Colchicine through Rh‐Catalyzed Intramolecular [5+2] Cycloaddition,"Abstract A synthetic approach towards (5 R )‐5‐methyl‐6‐oxa‐desacetamido colchicine as a conformationally defined non‐natural colchicine analog with a modified B‐ring was undertaken. The synthetic strategy was based on a Rh‐catalyzed cascade reaction involving a [5+2] cycloaddition of a carbonyl ylide intermediate as a key step, in which both seven‐membered rings of the polycyclic framework are formed in a single operation. Starting from 2‐iodo‐3,4,5‐trimethoxy‐acetophenone, an upper side‐chain was constructed through enantioselective CBS reduction (up to 75 % ee ) and propargylation, while a lower succinoyl side‐chain was attached either throughiodine–magnesium–copper exchange and subsequent reaction with methyl 4‐chloro‐4‐oxobutanoate, or by Pd‐catalyzed Stille cross‐coupling with 2‐tributylstannyl‐5‐methoxyfuran followed by hydrolytic furan‐opening. Treatment of an α‐diazoketone intermediate with Rh 2 (OAc) 4 (3 mol‐%)initiated the diastereoselective key cyclization cascade (≥97:3 dr ). Treatment of the cycloadduct 3 with Et 2 AlCl afforded an interesting 11,12‐dihydrocolchicine analog 24 , which, however, could not be oxidized to the corresponding tropolone. Structural assignments were confirmed by X‐ray crystallography. While compounds 3 and 24 did not exhibit noteworthy cytotoxic activity by themselves, they were found to strongly enhance the cytostatic (apoptosis‐inducing) activity of doxorubicin against resistant Nalm‐6 cells (i.e., in a synergy effect).",10.1002/ejoc.201200677,2012-07-09,0.5914212736987217
Organic Letters,Synthesis of Novel Polyyne Analogues of Sphingoid Base via an Iterative Acetylene Homologation Sequence,"The first syntheses of polyyne-containing sphingoid base analogues were achieved by employing our iterative strategy that uses a two-step acetylene homologation sequence. In this process, a bromoalkyne is homologated by one acetylene unit through a Pd-catalyzed cross-coupling with a TIPS-protected acetylene and a subsequent in situ AgF-mediated desilylative bromination. Repeating this homologation sequence followed by cross-coupling with the long-chained terminal acetylene provides access to the polyyne framework in good overall yields.",10.1021/ol070608d,2007-05-01,0.5914208499611948
Journal of the American Chemical Society,Synthesis of (+)-Cortistatin A,"Cortistatin A is a marine steroid with highly selective and perhaps mechanistically unique antiangiogenic activity. Herein we report a synthesis of this natural product by way of ""cortistatinone"", an intermediate ideally suited for investigating the key pharmacophore of the cortistatin family. The synthesis begins with a terrestrial steroid and traverses a route to cortistatin A through the discovery of unique chemical reactivity. Specifically, we demonstrate the first example of a directed, geminal C-H bisoxidation, a new fragmentation cascade to access expanded B-ring steroid systems, a chemoselective cyclization to install the hallmark oxabicycle of the cortistatin family, and a remarkably selective hydrogenation reaction, which should find extensive use in future syntheses of the cortistatins and designed analogues. The synthesis displays a level of brevity, efficiency, and practicality that will be crucial in evaluating the medicinal potential of this fascinating class of marine steroids.",10.1021/ja8023466,2008-05-14,0.5914194766383293
Tetrahedron,"SCH 58450, a novel farnesyl protein transferase inhibitor possessing a 6a,12a:7,12-diepoxybenz[a]anthracene ring system",,10.1016/0040-4039(95)01589-a,1995-09-01,0.5914118878230724
Synlett,"One-Pot, Three-Component Synthesis of Chiral 4-Alkylidene-2-oxazolidinones","A one-pot convenient access to chiral 2-oxazolidinones is described. Diethylzinc-mediated asymmetric alkynylation of aldehydes with propiolates in the presence of β-sulfonamide alcohol as the chiral ligand, followed by treatment with isocyanates, yielded chiral 4-alkylidene-2-oxazolidinones.",10.1055/s-0029-1218353,2009-11-11,0.591402042817048
Organic Letters,Concise Synthesis of the Bacterial DNA Primase Inhibitor (+)-Sch 642305,"[structure: see text]. A highly convergent, enantioselective synthesis of (+) -Sch 642305 is presented, which features a Mukaiyama-Michael addition followed by allylation to establish the syn-anti relationship of the three contiguous stereocenters. The 10-membered macrolactone was formed through ring-closing metathesis.",10.1021/ol070173u,2007-03-01,0.5913983615324777
Tetrahedron,"Facile synthesis of 1,3-diacetyl-2-methylcyclopentene a versatile synthetic intermediate.",,10.1016/s0040-4039(01)91324-3,1981-01-01,0.5913969167527274
Tetrahedron,"New simple and inexpensive synthetic route, mediated by sulfur, to enantiopure (−)-conduritol E derivative from D-mannitol",,10.1016/s0040-4039(97)10040-5,1997-11-01,0.5913918256083017
Angewandte Chemie International Edition,"Synthesis of the Protein Phosphatase 2A Inhibitor (4S,5S,6S,10S,11S,12S)-Cytostatin",Reagent-controlled reactions are key to the introduction of the stereocenters in the total synthesis of the cytostatin isomer 1. The stereochemical flexibility of the synthesis allows efficient and convenient access to other isomers.,10.1002/1521-3773(20020517)41:10<1748::aid-anie1748>3.0.co;2-x,2002-05-17,0.5913877680976213
Journal of Organic Chemistry,"Highly Chemoselective Trichloroacetimidate-Mediated Alkylation of Ascomycin:  A Convergent, Practical Synthesis of the Immunosuppressant L-733,725","L-733,725, a new immunosuppressant drug candidate, was prepared by a highly chemoselective alkylation of the macrolide ascomycin at the C32 hydroxy position with the imidazolyl trichloroacetimidate 16. The trichloroacetimidate-activated side chain 16 was prepared by an efficient four-step sequence in 42% overall yield. The high chemoselectivity in the alkylation of the C32 hydroxy group of the unprotected ascomycin was the result of the synergetic effects of the electron-donating protecting group on the imidazole 16, the polar, moderately basic solvent, and the strong acid catalyst. N,N-Dimethylpivalamide mixed with acetonitrile was found to be the best solvent and trifluromethanesulfonic acid the best catalyst. This synthesis coupled with a resin column purification of L-733,725 followed by crystallization of its tartrate salt has been used to make multi-kilogram quantities of the bulk drug with consistent and high purity.",10.1021/jo981805g,1999-02-25,0.5913868149437853
Angewandte Chemie International Edition,"Thiourea‐Catalyzed Asymmetric Michael Addition of Carbazolones to 2‐Chloroacrylonitrile: Total Synthesis of 5,22‐Dioxokopsane, Kopsinidine C, and Demethoxycarbonylkopsin","Abstract A modified Takemoto catalyst enabled the asymmetric Michael addition of carbazolones to 2‐chloroacrylonitrile to afford 3,3‐disubstituted carbazolones with excellent enantioselectivity. This method was successfully applied to total syntheses of three Kopsia alkaloids which featured an unprecedented Mn III ‐mediated oxidative cyclization to create the caged ring system and a SmI 2 ‐mediated reductive coupling as key steps.",10.1002/anie.201805905,2018-06-19,0.5913828375819513
Organic Letters,Asymmetric Total Synthesis and Absolute Stereochemistry of the Neuroactive Marine Macrolide Palmyrolide A,The first asymmetric total synthesis and determination of the absolute configuration for the neuroactive marine macrolide palmyrolide A is described. The highlight of the synthesis is macrocyclization via trans-enamide formation catalyzed by copper(I) iodide and cesium carbonate. Comparison with the authentic spectral data confirms the synthesis of (+)-ent-palmyrolide A.,10.1021/ol300673m,2012-04-04,0.591380123605124
Angewandte Chemie International Edition,Enantioselective Synthesis of Dithia[5]helicenes and their Postsynthetic Functionalization to Access Dithia[9]helicenes,"A highly enantioselective synthesis of 5,13-disubstituted dibenzo[d,d']benzo[1,2-b:4,3-b']dithiophenes is reported. Key for the successful assembly of these helical architectures is the last two successive Au-catalyzed intramolecular alkyne hydroarylation events. Specifically, the second cyclization is the enantiodetermining step of the whole process and provides the desired helicenes with excellent ee values when a TADDOL-derived 1,2,3-(triazolium)phosphonite moiety (TADDOL: α,α,α',α'-tetraaryl-1,3-dioxolane-4,5-dimethanol) is employed as an ancillary ligand. The absolute stereochemistry of the newly prepared structures has been determined by X-ray crystallography to be P; the optical properties of these heterohelicenes are also reported. A three-step procedure was subsequently developed that allows the transformation of the initially obtained dithia[5]helicenes into dithia[9]helicenes without erosion of the enantiopurity.",10.1002/anie.202114577,2021-12-07,0.5913800057724816
European Journal of Organic Chemistry,Stereodivergent Total Synthesis of (+)‐Aspergillide B and (+)‐7‐<i>epi</i>‐Aspergillide A,"Abstract The stereoselective total syntheses of (+)‐aspergillide B and (+)‐7‐epi‐aspergillide A were achieved. The key reactions include Noyori's asymmetric transfer hydrogenation, an Achmatowicz rearrangement, a Ferrier‐type alkynylation, a hydrosilylation–protodesilylation, a CBS (Corey–Bakshi–Shibata) oxazaborolidine reduction, a Yamaguchi macrolactonization, and a Mitsunobu macrolactonization.",10.1002/ejoc.201201155,2012-11-27,0.5913790373734613
Organic Letters,Enantioselective Synthesis of Spiroacetals via Silver(I)-Promoted Alkylation of Hemiacetals: Total Synthesis of Cephalosporolides E and F,"A silver(I)-promoted intramolecular hemiacetal alkylation has been developed that converts readily available keto-chlorodiols into functionalized spiroacetals containing 5,5-, 5,6-, and 5,7-membered ring systems. The efficiency of this process is demonstrated in a concise total synthesis of the fungal metabolites cephalosporolides E and F.",10.1021/ol302694s,2012-11-12,0.5913786692223765
Journal of Organic Chemistry,Synthesis of the Ring C Pyrrole of Native Chlorophylls and Bacteriochlorophylls,"As part of a program to develop practical syntheses of members of the family of (bacterio)chlorophylls, two routes to 2-iodo-3-methyl-4-(3-methoxy-1,3-dioxopropyl)pyrrole, a precursor of the universal ring C, have been developed. The β-ketoester of ring C is expected to give rise to ring E upon Knoevenagel condensation and Nazarov cyclization with a ring D constituent as demonstrated in an analogue synthesis. Two viable routes were developed beginning with N -TIPS-pyrrole or with 4-oxo-2-pentene and TosMIC, affording multi-gram-quantities of this ostensibly simple pyrrole.",10.1021/acs.joc.9b01650,2019-08-21,0.5913772558053638
Journal of Organic Chemistry,"Enantioselective Total Syntheses of (<i>+</i>)-Arborescidine A, (−)-Arborescidine B, and (−)-Arborescidine C","Described are the first enantioselective total syntheses of (+)-arborescidine A ((+)-1), (-)-arborescidine B ((-)-2), and (-)-arborescidine C ((-)-3), via routes that proceeded in five steps and 50% overall yield, eight steps and 61% overall yield, and nine steps and 51% overall yield, respectively, from 6-bromotryptamine (7). The syntheses feature the use of the Noyori catalytic asymmetric hydrogen-transfer reaction to introduce chirality in dihydro-beta-carbolines 6 and 8. On the basis of an ample precedent from Noyori's work, the reduction produces dihydro-beta-carbolines, and ultimately the natural products, possessing the R absolute configuration. The synthetic arborescidines displayed optical rotations that were opposite in sign those of the natural products, thereby supporting the S configuration for natural arborescidines A (1) and B (2) and the (3S,17S) configuration for natural arborescidine C (3). Our results are in agreement with the initial stereochemical assignment by Païs and co-workers, and are counter to their recently revised assignment.",10.1021/jo035165f,2004-01-28,0.5913742574749038
Synthesis,Protecting-Group-Free Synthesis of GB1107: An Orally Active Galectin-3 Antagonist,"Abstract Small-molecule galectin inhibitors are useful research tools that could also be used as potential drug candidates. In that context, GB1107, a monosaccharidic galectin inhibitor, was shown to be an orally active galectin-3 antagonist that inhibits lung adenocarcinoma growth. Herein, a protecting-group-free synthesis of GB1107, along with other analogues is described. Starting from inexpensive levoglucosan, a Payne rearrangement/azidation process was used as key step. Finally, the use of a log P determination method based on 19F NMR spectroscopy was explored to assess the lipophilicity of galectin inhibitors.",10.1055/a-1517-7177,2021-05-26,0.5913710924053631
Tetrahedron,A macrocyclic receptor for the chiral recognition of hydroxycarboxylates,,10.1016/s0040-4039(00)00693-6,2000-06-01,0.5913707863434559
Organic Letters,"Cross-Dehydrogenative Cyclization–Dimerization Cascade Sequence for the Synthesis of Symmetrical 3,3′-Bisoxindoles","The synthesis of symmetrical 3,3′-bisoxindoles from simple acyclic β-oxoanilides is reported. The described method forges three new C–C bonds in a single step via a sequential Mn(OAc) 3 · 2H 2 O mediated oxidative radical cyclization-fragmentation–dimerization process. The scope of this reaction is demonstrated in the preparation of a variety of 3,3′-bisoxindoles, as well as its application toward the formal synthesis of the Calycanthaceae alkaloid, (±)-folicanthine.",10.1021/acs.orglett.1c01799,2021-07-07,0.5913658358470877
Organic Letters,An Enantioselective Total Synthesis of Helioporins C and E,"A short and enantioselective total synthesis of helioporins C and E, which are bioactive marine diterpenes containing a serrulatane or amphilectane skeleton, was elaborated. The chirogenic step, i.e. a Cu(I)-catalyzed allylic alkylation of a cinnamyl chloride with methylmagnesium bromide, proceeded with virtually complete enantioselectivity (99% ee) in the presence of a chiral phosphine-phosphite ligand. The other stereocenters were diastereoselectively established through Me(2)AlCl-mediated cationic cyclization and Ir-catalyzed hydrogenation.",10.1021/ol302898h,2012-11-13,0.5913651524011747
Journal of the American Chemical Society,"Interphylal Product Splicing:  The First Total Syntheses of Cephalostatin 1, the North Hemisphere of Ritterazine G, and the Highly Active Hybrid Analogue, Ritterostatin G<sub>N</sub>1<sub>N</sub><sup>1</sup>","Convergent total syntheses of the extremely potent cell growth inhibitor cephalostatin 1 and two hybrid analogues, ritterostatins G N 1 N and G N 1 S, have been achieved. Ritterostatin G N 1 N displays sub-nanomolar activity in the 60 cell line human tumor panel of the National Cancer Institute. The North hemisphere of ritterazine G was efficiently constructed from hecogenin acetate in 15% yield over 13 steps. Extension of a key photolysis/Prins sequence to intermediates 19 and 32 proceeded in excellent yield, leading to installation of the Δ 14 moiety in the North G and South 1 steroidal subunits. Application of a method for directed unsymmetrical coupling furnished the natural and analogue pyrazines in good yield from the cephalostatin and ritterazine components.",10.1021/ja972160p,1998-01-17,0.5913598945350111
Journal of the American Chemical Society,Teubrevin G and Teubrevin H:  The First Total Syntheses of Rearranged <i>n</i><i>eo</i>-Clerodanes Including Solutions to the Problems of Chirality Merger and Furan Ring Assembly,"Total syntheses of teubrevins G (2) and H (3) are described. The reported strategy relies on a highly regioselective cycloaddition-fragmentation approach to the construction of a 2,3,4-trisubstituted furan and features efficient ring-closing metathesis chemistry made possible through the application of a 1,3-dimesityl-4,5-dihydroimidazol-2-ylideneruthenium precatalyst. The key building blocks 39 and 48 were constructed by asymmetric processes and coupled under conditions where good remote asymmetric induction was realized. The diastereoselection observed in this alkylation reaction appears to be intimately associated with the conformational properties of the beta-keto ester enolate. While the readily separated major diastereomer was transformed via a short route to 2, the minor component served as the precursor to 3. The efficiency of the synthesis was thereby well served.",10.1021/ja010313+,2001-04-12,0.591356892389896
Synthesis,"A New Synthesis of Methyl 7H-Dibenz[b,g]oxocin-6-carboxylates from Morita-Baylis-Hillman Adducts of 2-Phenoxybenzaldehydes","A new synthetic method for methyl 7H-dibenz[b,g]oxocin-6-carboxylates by Friedel-Crafts reaction of readily available bromides of Morita-Baylis-Hillman adducts with aluminum chloride has been developed.",10.1055/s-0030-1258392,2011-01-05,0.5913491611847084
Tetrahedron,Multigram synthesis of an advanced nitroalkene intermediate: application in synthesis of octahydroindol-2-one derivative featuring diastereoselective Michael addition of diethylmalonate,,10.1016/j.tetlet.2016.04.055,2016-04-22,0.5913482104219273
Organic Letters,Magnesiate-Utilized/Benzyne-Mediated Approach to Indenopyridones from 2-Pyridones: An Attempt To Synthesize the Indenopyridine Core of Haouamine,"An efficient, short-staged synthesis of cis -fused indeno[2,1- b ]- and indeno[1,2- c ]pyridin-2-ones, starting from 2-pyridones, using magnesiates of type R 3 MgLi as nucleophilic and deprotonation agents, mediated by benzyne generated in situ, under optimized conditions, is described. Following the developed protocol, rare C4a-arylsubstituted indeno[2,1- b ]pyridones, resembling the core of haouamine, were obtained. The protocol offering the one-pot synthesis directly from 2-pyridone is also described.",10.1021/acs.orglett.9b03806,2019-11-20,0.5913430214032903
Journal of Organic Chemistry,Application of Negishi Cross-Coupling to the Synthesis of the Cyclic Tripeptides OF4949-III and K-13,"Syntheses of the cyclic tripeptides OF4949-III 1 and K-13 2 are reported, in which the key steps are intermolecular and intramolecular Negishi cross-coupling reactions, respectively. In addition, the synthesis of a protected isomer of K-13 25 is reported. The synthesis of K-13 features a tripeptidic organozinc reagent 11, one of the most highly functionalized such reagents to be described. An O-aryltyrosine derivative 15, prepared by S(N)Ar reaction between Boc-tyrosine and 2-fluorobenzaldehyde, followed by Dakin reaction, iodination, and methylation, is used as a common intermediate for all of the syntheses described. The routes to this class of cyclic tripeptide are among the shortest reported to date and demonstrate the high functional group tolerance of the carbon-zinc bond toward peptide derivatives.",10.1021/jo9018792,2009-10-08,0.5913419134941407
Synthesis,Synthesis of<i>N</i>-[2-(6-Chloro-5-methoxy-1<i>H</i>-indol-3-yl)]ethyl-acetamide (6-Chloromelatonin),,10.1055/s-1983-30579,1983-01-01,0.5913402904288304
Organic Letters,"Total Synthesis of Cyanthiwigins A, C, G, and H","The first total synthesis of cyanthiwigins A, C, H and concise synthesis of cyanthiwigin G was achieved from a common intermediate. A modified formal [4 + 2] cycloaddition was developed to construct the key cis-hydrindanone (A-B). Stereospecific 1,4-addition, alkylation, and ring-closing metathesis were used to build the tricarbocyclic ring system (A-B-C). Various site-selective oxidations were applied to create the desired oxidation states of the different cyanthiwigins.",10.1021/ol4019425,2013-08-15,0.591339062613355
Journal of the American Chemical Society,Nondynamic and Dynamic Kinetic Resolution of Lactones with Stereogenic Centers and Axes:  Stereoselective Total Synthesis of Herbertenediol and Mastigophorenes A and B,"The stereoselective total synthesis of the sesquiterpene herbertenediol ( 3 ) and of its naturally occurring dimers, mastigophorenes A [( P )- 1 ] and B [( M )- 1 ], is described. Following the “lactone concept”, the configuration at the biaryl axis was atropo-divergently induced to be P or, optionally, M, by stereocontrolled reductive ring cleavage (diastereomeric ratio up to 97:3) of the configurationally unstable joint biaryl lactone precursor 17 using the oxazaborolidine−borane system, through dynamic kinetic resolution. Mechanistic considerations of the lactone coupling suggested interference by a methoxy group next to the halogen substituent and led to an improvement of the coupling yield from 39 to 87% (to give the lactone 37 ). As a new, likewise highly efficient variant of the lactone method, we report for the first time the now nondynamic kinetic resolution of a structurally related, but centrochiral “aliphatic−aromatic” lactone, ( rac )- 10 . Its highly efficient ( k rel > 300) enantiomer-differentiating Corey−Bakshi−Shibata reduction delivers the centrochiral building block ( R,R )- 10 in good chemical yield and with excellent stereochemical purity (enantiomeric excess > 99.9%; enrichment of the starting matrial). The new synthesis of natural herbertenediol ( 3 ) confirms its absolute stereostructure as well as that of its dimers, ( P )- 1 and ( M )- 1 .",10.1021/ja001455r,2000-09-01,0.5913383715506775
Journal of Organic Chemistry,Synthetic Studies on Actinobolin and Bactobolin:  Synthesis of <i>N</i>-Desalanyl-<i>N</i>-[2-(trimethylsilyl)ethanesulfonyl] Derivatives from a Common Intermediate and Attempted Removal of the SES Protecting Group,"Two closely related syntheses of 5,6- O -(2-propylidene)- N -desalanyl- N -2-(trimethylsilyl)ethanesulfonyl]bactobolin ( 9b ) from (+)- 12, an intermediate previously prepared from d -glucose, are reported. In each case, the key step involves a precedented stereoselective addition of LiCHCl 2 in the presence of CeCl 3 to a suitably protected α-amino ketone. Intermediates from both synthetic routes to 9b can be prepared by degradation of actinobolin ( 2 ) thereby establishing a potential method for the transformation of actinobolin into bactobolin. An efficient route to 5,6- O -(2-propylidene)- N -desalanyl- N -[[2-(trimethylsilyl)ethanesulfonyl]actinobolin ( 7b ) from (+)- 12 involving an unexpected cyclization of 29 was discovered. The 2-(trimethylsilyl)ethanesulfonyl (SES) protecting group in 7b was removed by reaction with Bu 4 NF in wet THF. The nature of the Bu 4 NF reagent was found to be important to the outcome of the reaction. Several improvements over our previously reported synthesis of actinobolin from d -glucose are noted. Although precedented, the removal of the SES protecting group from 9b could not be achieved thereby preventing completion of a total synthesis of bactobolin.",10.1021/jo960579c,1996-01-01,0.591338260594382
Journal of the American Chemical Society,Total Synthesis of Apratoxin A,"Apratoxin A, a cyclodepsipeptide isolated from cyanobacterial Lyngbya spp, has been synthesized. The total synthesis features stereocontrolled access to the novel polyketide and the late-stage installation of the sensitive 2,4-disubstituted thiazoline moiety using an intramolecular Staudinger reduction/aza-Wittig process.",10.1021/ja036050w,2003-06-26,0.5913309291113242
Organic Letters,Isochromenylium/Isoquinolinium-Mediated One-Pot Annulation to Hexahydropyrazinoisoquinolines. Synthesis of Quinocarcinol,"A novel annulation protocol has been successfully developed in this work for the quick generation of 1,3,4,6,11,11a-hexahydro-2 H -pyrazino[1,2- b ]isoquinolines from easily accessible o -alkynylbenzaldehydes. Various hexahydropyrazinoisoquinolines, including those previously unavailable with electron-deficient substituents, have been achieved via the newly developed continuously operational isochromenylium/isoquinolinium-mediated procedure. It also perfectly served as a key step to generate the basic skeleton in the new total synthesis of quinocarcinol, accompanied by the development and application of a direct late-stage stereoselective sp 3 C–H hydroxymethylation.",10.1021/acs.orglett.3c03368,2023-12-06,0.5913258184125153
Journal of Organic Chemistry,Synthesis of Carbapyochelins via Diastereoselective Azidation of 5-(Ethoxycarbonyl)methylproline Derivatives,Two configurationally stable carbon-based analogues of pyochelin have been prepared from Boc-pyroglutamic acid-tert-butyl ester in 11 and 13 steps. Introduction of the amino group was achieved by a highly diastereoselective electrophilic azidation reaction to afford novel bis-alpha-amino acid proline derivatives.,10.1021/jo801294p,2008-08-13,0.5913242531602718
Tetrahedron,"Phenoxide-mediated Sonogashira coupling of trimethylsilylalkynes and aryliodides: practical synthesis of phenolic-hydroxy-substituted diarylethynes and 1,4-diarylbutadiynes",,10.1016/j.tetlet.2013.01.091,2013-01-30,0.5913166804513244
Tetrahedron,"Ni(COD)2 coupling of 3,6-dibromocarbazoles as a route to all-carbazole shape persistent macrocycles",,10.1016/j.tetlet.2015.08.048,2015-08-21,0.5913136491993344
Synlett,Use of Nitriles in Synthesis. First Total Synthesis of <i>ent</i>-Sachalinol A,"The total synthesis of ent-sachalinol A, has been achieved by utilizing a Sharpless epoxidation and nitrile substitution as the key reactions.",10.1055/s-2006-944223,2006-07-01,0.5913115476398594
Journal of Organic Chemistry,A Short Synthesis of Vellosimine and Its Derivatives,Rapid access to both enantiomers of vellosimine and its derivatives is secured from a readily affordable C 2 -symmetric 9-azabicyclo[3.3.1]nonane precursor available in both enantiomeric forms. The strategy reported leverages desymmetrization via intramolecular cyclization used to assemble the key intermediate with two differentiated carbonyl groups. Late-stage site selective indolization enables a concise synthesis of vellosimines and a straightforward diversification of the alkaloid scaffold.,10.1021/acs.joc.3c00905,2023-06-02,0.5913092907368824
Synlett,Formal Synthesis of the Bryostatin Northern Hemisphere: Asymmetric Synthesis of the B Ring and C1-C9 Fragment,"A formal synthesis of the top half fragment of bryostatin 11 has been developed. Stereoselective construction of the B ring was achieved by using a ring-closing metathesis reaction in conjunction with asymmetric glycolate alkylation. Furthermore, the C1-C9 fragment was synthesized by Brown allylation, chelation-controlled aldol condensation, and Saksena-Evans reduction to construct all stereogenic centers.",10.1055/s-0030-1260586,2011-05-26,0.5913090984705718
Journal of Organic Chemistry,"Synthesis of Conformationally Restricted 2,3-Diarylbenzo[<i>b</i>]furan by the Pd-Catalyzed Annulation of <i>o</i>-Alkynylphenols:  Exploring a Combinatorial Approach","The palladium/bpy-catalyzed annulation of o-alkynylphenol with various aryl halides to generate diversified 2,3-diarylbenzo[b]furan is herein described. This method provides an efficient synthetic pathway for the combinatorial synthesis of conformationally restricted 2,3-diarylbenzo[b]furan for drug discovery.",10.1021/jo0303160,2004-03-09,0.5913021375845522
Tetrahedron,Total synthesis of the angiotensin-converting enzyme inhibitor A58365A: On the use of pyroglutamate as a chiral educt,,10.1016/s0040-4039(01)80464-0,1989-01-01,0.5912964744958527
Angewandte Chemie International Edition,"Total Synthesis of Polycephalin C and Determination of the Absolute Configurations at the 3″,4″ Ring Junction","Only through total synthesis could the absolute configuration of the 3″R,4″R ring junction of the polyenoltetramic acid polycephalin C (1) be unambiguously established. Key features of the synthesis include a double Swern oxidation, double Stille coupling, and a double Takai olefination.",10.1002/1521-3773(20020802)41:15<2786::aid-anie2786>3.0.co;2-z,2002-08-02,0.591294511647591
Organic Process Research & Development,Kilogram-Scale Preparation of an Aminopyrazole Building Block via Copper-Catalyzed Aryl Amidation,"We describe a scalable method for preparing an aminopyrazole building block using copper-catalyzed amidation with acetamide as an ammonia surrogate. This procedure provides an alternative to the standard nitration/reduction sequence and avoids energetic intermediates, specialized hydrogenation equipment, and potentially genotoxic impurities that arise from nitro reduction. The chemistry has been successfully scaled to produce >50 kg of the target compound and demonstrate the viability of this alternative route.",10.1021/acs.oprd.1c00066,2021-04-06,0.5912900129828419
Organic Letters,Total Synthesis of (+)-Nafuredin-γ Using a Highly Stereoselective Ti-Mediated Aldol Reaction,"An efficient total synthesis of (+)-nafuredin-γ has been achieved in 10 steps from (E)-3-(tributylstannyl)propenal. The synthesis features direct construction of an anti-1,2-diol moiety via a Ti-mediated aldol reaction of lactyl derivative and rapid fragment assembly, which relied on well-established Pd chemistry.",10.1021/ol102501k,2010-12-07,0.5912867726990333
Organic Letters,Indolizine Synthesis via Oxidative Cross-Coupling/Cyclization of Alkenes and 2-(Pyridin-2-yl)acetate Derivatives,"A novel copper/I2-mediated oxidative cross-coupling/cyclization of 2-(pyridin-2-yl)acetate derivatives and simple olefins is developed, which provides a straightforward and efficient access to structural diversely indolizines. A series of 1,3-di- and 1,2,3-trisubstituted indolizines are easily synthesized in modest to excellent yields.",10.1021/acs.orglett.5b01334,2015-06-11,0.5912849631910164
Tetrahedron,A concise asymmetric route to the antibiotic macrolides patulolide A and pyrenophorin,,10.1016/j.tetlet.2006.07.026,2006-08-02,0.5912822250532569
Organic Letters,A Palladium-Catalyzed Carbo-oxygenation: The Bielschowskysin Case,"An asymmetric synthesis of an advanced tetracyclic intermediate toward the synthesis of bielschowskysin (1) is described. A biomimetic [2 + 2]-photocyclization was used to establish the cyclobutane core of bielschowskysin. Macrocyclization under Heck conditions led to an unprecedented carbo-oxygenation of a 1,1-disubstituted double bond.",10.1021/ol401285d,2013-05-31,0.5912780908409314
Organic Letters,Synthesis of (−)-Epibatidine,The synthesis of (-)-epibatidine has been accomplished utilizing a highly exo-selective asymmetric hetero Diels-Alder reaction. The key steps employed to transform the resulting bicycle into the natural product include a fluoride-promoted fragmentation and a Hofmann rearrangement. Reaction: see text.,10.1021/ol016420q,2001-08-30,0.591274305497819
Journal of the American Chemical Society,Scalable Total Synthesis of (−)-Vinigrol,"Vinigrol is a structurally and stereochemically complex natural product that displays various potent pharmacological activities, including the capability to modulate TNF-α. A new and efficient synthetic route toward this natural product has been developed to complete the asymmetric synthesis of (-)-vinigrol and provide over 600 mg of material, manifesting the power of macrocyclic stereocontrol and transannular Diels-Alder reaction.",10.1021/jacs.9b00621,2019-02-15,0.5912709919488944
Organic Letters,"Synthesis of Thelepamide via Catalyst-Controlled 1,4-Addition of Cysteine Derivatives and Structure Revision of Thelepamide","The first enantioselective total synthesis and structural reassignment of (-)-thelepamide, a cytotoxic tetraketide-amino acid from the marine worm Thelepus crispus, is reported. A convergent approach provides access to all thelepamide diastereomers in six steps from four simple building blocks. Key features of the synthesis include the application of Melchiorre's organocatalytic thia-Michael reaction and a sonication-assisted assembly of an unprecedented N,O-acetal-hemiacetal moiety. The corrected structure was confirmed by NMR-DFT analysis.",10.1021/acs.orglett.7b03706,2018-01-10,0.5912677279102141
Journal of Organic Chemistry,"First Asymmetric Total Synthesis of Synerazol, an Antifungal Antibiotic, and Determination of Its Absolute Stereochemistry","[reaction: see text] By synthesizing two possible diastereomers, the first asymmetric total synthesis of synerazol, an antifungal antibiotic, has been accomplished, allowing determination of its absolute stereochemistry. A more practical second generation route was also established. The key steps are racemization-free deprotection of a TIPS group and introduction of a methyl ether by DMD oxidation of the benzylidene moiety in a substrate having a small protecting group.",10.1021/jo050664x,2005-06-08,0.5912677109341646
Journal of Organic Chemistry,Total Synthesis of Mulberry Diels–Alder-Type Adducts Kuwanons G and H,"Mulberry Diels–Alder-type adducts (MDAAs) are a group of rare natural polyphenols biosynthetically derived from [4 + 2]-cycloaddition of chalcones and dehydroprenylphenols. In this study, kuwanons G ( 1 ) and H ( 2 ), two bioactive MDAAs with unique dehydroprenylflavonoid dienes, were totally synthesized for the first time in a biomimetic manner. The key features of the convergent route include the use of the Baker–Venkataraman rearrangement, alkylation of β-diketone, intramolecular cyclization, and Suzuki–Miyaura coupling to achieve the subunit diene.",10.1021/acs.joc.1c00229,2021-03-10,0.5912632797346159
Tetrahedron,Preparation of an advanced intermediate for the synthesis of epi-thromboxanes,,10.1016/s0040-4039(98)00599-1,1998-05-01,0.5912589978426084
Journal of Organic Chemistry,Synthesis of the<i>C</i>-Linked Disaccharide α-<scp>d</scp>-Man-(1→4)-<scp>d</scp>-Man Employing a SmI<sub>2</sub>-Mediated<i>C</i>-Glycosylation Step:  En Route to Cyclic<i>C</i>-Oligosaccharides,"Investigations are reported on the assembly of the C-linked disaccharide alpha-D-Man-(1-->4)-D-Man, representing the first steps in our projected synthesis of a cyclic C-oligomer containing repeating units of this C-dimer. The key step in this synthesis uses a SmI(2)-mediated coupling of 2,3,4,6-tetra-O-benzyl-alpha-D-mannopyranosyl 2'-pyridyl sulfone with a C4-formyl branched mannopyranoside unit, affording the C-disaccharide derivative with complete stereocontrol at the two new stereogenic centers. Subsequently, a modified tin hydride based deoxygenation produced the target carbohydrate analogue. The synthesis of the C4-formyl monosaccharide makes use of a stereoselective radical-based allylation followed by double bond migration and ozonolysis.",10.1021/jo020585a,2003-02-01,0.5912548278900639
Journal of the American Chemical Society,Total Synthesis of (−)-Rhodomollanol A,"An asymmetric approach for the first total synthesis of (−)-rhodomollanol A, a highly oxidized diterpenoid, is described. The efficient synthetic strategy features three key transformations: (1) an oxidative dearomatization-induced (5 + 2) cycloaddition/pinacol-type 1,2-acyl migration cascade to build up the bicyclo[3.2.1]octane skeleton; (2) a retro -Dieckmann fragmentation/vinylogous Dieckmann cyclization cascade to assemble the bicyclo[3.3.0]octane subunit; and (3) a photo-Nazarov cyclization/intramolecular cycloetherification cascade to forge the 7-oxabicyclo[4.2.1]nonane core structure of the natural product.",10.1021/jacs.0c00308,2020-02-24,0.591253106490487
European Journal of Organic Chemistry,"Copper Catalyzed Assembly of <i>N</i>‐Aryloxazolidinones: Synthesis of Linezolid, Tedizolid, and Rivaroxaban","Abstract The total synthesis of oxazolidinone‐based pharmaceuticals, linezolid, tedizolid and rivaroxaban is reported. They are synthesized using a recently reported copper‐catalyzed one‐pot cyclization and arylation as the key step to construct the N ‐aryloxazolidinone core. Active pharmaceutical ingredients (API) were synthesized from a common synthetic pool of a simple protected amino alcohol in 22 %, 61 % and 40 % total synthesis yields, respectively.",10.1002/ejoc.201600033,2016-02-09,0.5912489759225381
Tetrahedron,A new and efficient route toward the preparation of diazo ketones using cyanuric chloride and diazomethane,,10.1016/s0040-4039(00)01791-3,2000-12-01,0.591245214638498
Journal of Organic Chemistry,Two-Step Synthesis of Aza- and Diazaindoles from Chloroamino-<i>N</i>-heterocycles Using Ethoxyvinylborolane,"An efficient two-step route to a broad range of aza- and diazaindoles was established, starting from chloroamino-N-heterocycles, without the need for protecting groups. The method involves an optimized Suzuki-Miyaura coupling with (2-ethoxyvinyl)borolane followed by acetic acid-catalyzed cyclization.",10.1021/jo902143f,2009-12-01,0.591240425195017
Synlett,Synthesis of Marine Oxylipins Constanolactones C and D,"After providing the marine oxylipins constanolactones A and B, the next two members of this family were synthesized for the first time. Key to the success was a highly enantioselective and Z-selective reagent-controlled allyl addition (>99%) en route to the aliphatic side chain.",10.1055/s-2007-986647,2007-09-21,0.5912394337604743
Journal of the American Chemical Society,Total Synthesis of (−)-Crambidine and Definition of the Relative Configuration of Its Unique Tetracyclic Guanidinium Core,"Total syntheses of the 3S,8S,10S,19R,43S isomer 4a and the 3S,8S,10S,19R,43R isomer 4b of the unique crambescidin alkaloid crambidine are reported. These studies confirm the tetracyclic structure proposed by Braekman and co-workers for crambidine, and establish the rel-3R,8R,10R,19S relative configuration for this moiety. Natural crambidine is most likely the 3S,8S,10S,19R,43S isomer 4a. These syntheses were completed in five steps and approximately 14% overall yield from 1-iminohexahydro[1,2-c]pyrimidine carboxylic ester 10, an intermediate in our earlier total synthesis of 13,14,15-isocrambescidin 800 (3). The signature step in the total syntheses of crambidine and several stereoisomers is chemoselective dehydrogenation of the tethered Biginelli adduct 10 or the derived tetracyclic intermediate 17. Additionally, these studies reveal the unprecedented ring-chain isomerization of the crambidine ring system exemplified by the interconversion of isomers 15a and 15b.",10.1021/ja055464h,2005-10-14,0.5912383184770437
Tetrahedron,Endo selective cyclizations of selenonium ion intermediate: efficient formation of 1-halo-3-seleno-cyclohexanes,,10.1016/s0040-4039(00)71230-5,1991-01-01,0.5912378921312115
Journal of the American Chemical Society,Total Synthesis of (±)-Cycloclavine and (±)-5-<i>epi</i>-Cycloclavine,"Novel routes to the naturally occurring indole alkaloid cycloclavine and its unnatural C(5)-epimer are described. Key features include the rapid construction of the heterocyclic core segments by two Diels-Alder reactions. An indole annulation was accomplished by a late-stage intramolecular Diels-Alder furan cycloaddition, and a methylenecyclopropane dienophile was used for a stereoselective intramolecular [4 + 2] cycloaddition to give the cyclopropa[c]indoline building block present in cycloclavine.",10.1021/ja2026882,2011-04-25,0.5912327441951792
Organic Letters,Enantioselective Total Synthesis of RQN-18690A (18-Deoxyherboxidiene),"The first total synthesis of RQN-18690A (18-deoxyherboxidiene) and the determination of its absolute stereochemical configuration are described. The synthesis features an organocatalytic aldol reaction for the first step, 1,4- and 1,2- dual reductions of α,β-unsaturated δ-lactone followed by a domino reaction in a one-pot operation, and diastereoselective epoxidation with kinetic resolution.",10.1021/acs.orglett.6b01524,2016-07-05,0.5912155353976376
Organic Letters,Total Synthesis and Stereochemical Assignment of the Antimicrobial Lipopeptide Cerexin A<sub>1</sub>,"The isolation and total synthesis of the antimicrobial lipopeptide cerexin A1 is reported. This synthesis includes the preparation of orthogonally protected γ-hydroxylysine, utilizing a nitrile Reformatsky-type reaction as a key step to yield both diastereomers more efficiently than previously reported methods. The configuration of the β-hydroxyl in the lipid tail was determined by the use of a modified Ohrui-Akasaka approach. Furthermore, new cerexin analogues from Bacillus mycoides ATCC 21929 were isolated and characterized, revealing an ε-amino succinylation of a hydroxylysine residue that is unusual in a nonribosomal peptide synthetase product.",10.1021/acs.orglett.5b02779,2015-10-14,0.5912140760592743
Synlett,"Synthesis of the Selective Neuronal Nitric Oxide Synthase (nNOS) Inhibitor 5,6-Dibromo-2′-demethylaplysinopsin","The first synthesis of the selective neuronal nitric oxide synthase (nNOS) inhibitor 5,6-dibromo-2′-demethylaplysinopsin is described. The rare 5,6-dibromoindole moiety was constructed using a previously unused dibromination of an indole-3-carboxylate, the product of which was verified by X-ray crystallography. It was discovered the natural product was characterised as its trifluoroacetate salt in the isolation report.",10.1055/s-0030-1259913,2011-03-15,0.5912123800272995
Journal of Organic Chemistry,A Practical Total Synthesis of (+)-Spirolaxine Methyl Ether,"An efficient and practical total synthesis of (+)-spirolaxine methyl ether is described. The phthalide-aldehyde 3 has been prepared via the Diels-Alder reaction between 1,4-unconjugated diene 5 and a long-chain acetylenic dienophile 6. The carbon framework of spiroketal sulfone 4 has been constructed from monobenzyl protected 1,5-pentanediol and the stereochemistry in both the phthalide portion and the spiroketal portion has been established by the Sharpless asymmetric epoxidation.",10.1021/jo1016647,2010-11-08,0.5912026186682283
Organic Letters,Efficient Access to Cyclic Ureas via Pd-Catalyzed Cyclization,"[Structure: see text] An efficient regioselective method for the preparation of structurally diverse imidazopyridinones and benzoimidazolones starting from readily available and economical starting materials is described. High-yielding reductive alkylation of electron-deficient o-haloarylamines followed by treatment with inexpensive N-chlorosulfonyl isocyanate afforded primary ureas in good overall yields. A Pd-catalyzed urea cyclization reaction furnished imidazopyridinones and benzoimidazolones in excellent yields. Overall, the developed chemistry provides rapid access to pharmaceutically important heterocyclic compounds with high efficiency.",10.1021/ol061233j,2006-06-22,0.591202572073213
Journal of the American Chemical Society,A Convergent and Enantioselective Synthesis of (+)-Amurensinine via Selective C−H and C−C Bond Insertion Reactions,"A convergent and enantioselective synthesis of the natural product amurensinine is described. The synthetic strategy takes advantage of mild and selective C-H and C-C bond insertion reactions, in addition to the palladium-catalyzed aerobic oxidative kinetic resolution recently developed in these laboratories.",10.1021/ja0651815,2006-08-17,0.5911988624602527
Journal of Organic Chemistry,Total Synthesis of the Cytostatic Marine Natural Product Dibromophakellstatin via Three-Component Imidazolidinone Anellation,"The tetracyclic pyrrole-imidazole alkaloid dibromophakellstatin from the marine sponge Phakellia mauritiana has been synthesized within seven steps from pyrrole in an 18% overall yield. The key step is a three-component assembly of a tricyclic enamide, a nitrene, and a carbamoyl building block, affording the imidazolidinone ring of dibromophakellstatin in one step. Notably, it is possible to employ the reagent EtO2CNHOTs in a double function as a source of the electrophilic nitrene and of a dipolar carbamoyl component. Use of debrominated precursor dipyrrolopyrazinones leads to much higher anellation yields and allowed us to develop a second generation synthesis. The cytostatic activity of dibromophakellstatin is confirmed.",10.1021/jo061813u,2006-11-16,0.5911975005120294
Organic Letters,Aldolase-Catalyzed Synthesis of Conformationally Constrained Iminocyclitols: Preparation of Polyhydroxylated Benzopyrrolizidines and Cyclohexapyrrolizidines,"A straightforward chemo-enzymatic synthesis of new polyhydroxylated benzopyrrolizidines and cyclohexapyrrolizidines is developed. The two-step strategy consists of l-fuculose-1-phosphate aldolase variant F131A-catalyzed aldol addition of dihydroxyacetone phosphate to rac-N-benzyloxycarbonylindoline-2-carbaldehyde as well as (2S*,3aS*,7aS*)- and (2S*,3aR*,7aR*)-N-benzyloxycarbonyloctahydroindole-2-carbaldehydes and a subsequent one-step catalytic deprotection-reductive amination.",10.1021/ol5002158,2014-02-19,0.5911961229773303
Synthesis,"The Chemistry of Ethyl 3-(2-Ethoxy-2-oxoethyl)-1H-indole-2-carboxylate: Synthesis of Pyrimido[4,5-b]indoles and Diethyl 4-Hydroxyquinoline-2,3-dicarboxylate via Intramolecular Cyclizations","We report the synthesis of a new series of 2-oxo-1,2,4,9-tetrahydro-3 H -pyrimido[4,5- b ]indole derivatives and diethyl 4-hydroxyquinoline-2,3-dicarboxylate starting from ethyl 3-(2-ethoxy-2-oxoethyl)-1 H -indole-2-carboxylate. Intramolecular cyclization formed the target ring systems. The key substrates featuring both acyl azide and isocyanate functionalities were prepared from bis(acyl azide) intermediate. The acyl azide functionalities directly connected to methylene groups were regiospecifically converted into urea and urethanes via the reactive isocyanate intermediates. Thermal treatment of urea and urethanes provided the target 2-oxo-1,2,4,9-tetrahydro-3 H -pyrimido[4,5- b ]indoles. Furthermore, ozonolysis of the starting indolediester substrate and subsequent base treatment to diethyl 4-hydroxyquinoline-2,3-dicarboxylate are described.",10.1055/s-0036-1588119,2016-12-16,0.5911925854774759
Synlett,"Synthesis of the Icetexane Diterpenoids (±)-Rosmaridiphenol, (±)-Pisiferin, and (±)-Barbatusol from Abietane","Abstract We report the rearrangement of abietane core with trifluoromethanesulfonic anhydride in pyridine to afford the icetexane core, a key intermediate for total syntheses of the structurally intriguing and biologically active compounds (±)-barbatusol, (±)-rosmaridiphenol, and (±)-pisiferin.",10.1055/a-1801-4344,2022-03-17,0.5911911443457104
Tetrahedron,"On the acetoxylation of 2,3-dihydro-4-pyrones: a concise, fully synthetic route to the glucal stereochemical series",,10.1016/s0040-4039(00)98650-7,1985-01-01,0.5911805927925654
Journal of Organic Chemistry,"Copper-Catalyzed C–N Bond Formation/Rearrangement Sequence: Synthesis of 4<i>H</i>-3,1-Benzoxazin-4-ones","A facile and efficient copper-catalyzed method for the synthesis of 4H-3,1-benzoxazin-4-one derivatives has been developed. This procedure is based on a tandem intramolecular C-N coupling/rearrangement process. This method would provide a new and useful strategy for construction of N-heterocycles.",10.1021/jo400515y,2013-04-12,0.5911784745881209
Journal of Organic Chemistry,Synthesis of the Core Tetrasaccharide of<i>Trypanosoma</i><i>c</i><i>ruzi</i>Glycoinositolphospholipids: Man<i>p</i>(α1→6)-Man<i>p</i>(α1→4)-6-(2-aminoethylphosphonic acid)-GlcN<i>p</i>(α1→6)-<i>m</i><i>yo</i>-Ins-1-PO<sub>4</sub>,"[structure: see text] Synthesis of the core tetrasaccharide Manp(alpha1-->6)-Manp(alpha1-->4)-6-(2-aminoethylphosphonic acid)-GlcNp(alpha1-->6)-myo-Ins-1-PO4, found in glycoinositolphospholipids of Trypanosoma cruzi parasites, is described. The key building block, 6-O-(2-azido-3-O-benzyl-6-O-((2-benzyloxycarbonylaminoethyl)phosphonic acid benzyl ester)-2-deoxy-alpha-D-glucopyranosyl)-1-di-O-benzylphosphoryl-4,5-O-isopropylidene-2,3-O-(D-1,7,7-trimethyl[2,2,1]bicyclohept-6-ylidene)-D-myo-inositol, was synthesized using a partially protected glucosyl D-camphorinositolphosphate and a (2-benzyloxycarbonylaminoethyl)phosphonic acid derivative in a regioselective phosphonate esterfication. Elongation with ethyl 2-O-benzoyl-3,4,6-tri-O-benzyl-alpha-D-mannopyranosyl-(1-->6)-2,3,4-tri-O-benzyl-1-alpha-D-thiomannopyranoside using dimethyl(methylthio)sulfonium trifluoromethanesulfonate gave a fully protected tetrasaccharide which was successfully deprotected subsequently with sodium methoxide, sodium in liquid ammonia, and aq hydrochloric acid to give title compound.",10.1021/jo0508595,2005-08-11,0.591172485056263
Synthesis,An Efficient Synthesis of Functionalized 2-Pyridones by Direct Route or via Amide/Enolate Ammonium Salt Intermediates,All articles of this category mono and polycyclic 2-pyridones,10.1055/s-1999-3531,1999-07-01,0.5911720688858021
Tetrahedron,Synthesis of a new molecular carrier: N-(Leu-enkephalin)yl 6-amido-6-deoxy-cyclomaltoheptaose,,10.1016/s0040-4039(00)60440-9,1993-04-01,0.5911680487123583
Journal of Organic Chemistry,Progress toward the Total Synthesis of Psymberin/Irciniastatin A,"In this paper, we describe our synthesis of four key building blocks for the total synthesis of psymberin (1) and its C4 epimer (2). Despite early difficulties in processing material to the advanced intermediate stage, we have been successful in developing high-yielding syntheses for the pyran core, natural side chain, 4-epi side chain, and aryl fragments of the molecule. Our findings from the optimization process are presented herein.",10.1021/jo9009003,2009-07-02,0.5911664601487681
Journal of the American Chemical Society,Construction of Eight-Membered Ether Rings by Olefin Geometry-Dependent Internal Alkylation:  First Asymmetric Total Syntheses of (+)-3-(<i>E</i>)- and (+)-3-(<i>Z</i>)-Pinnatifidenyne,The first and highly stereoselective asymmetric total syntheses of eight-membered ring ether marine natural products (+)-3-(E)-pinnatifidenyne and (+)-3-(Z)-pinnatifidenyne have been accomplished. Notable features of our syntheses include a novel and efficient construction of oxocene 5 by a highly stereo- and regioselective internal alkylation and direct ketone synthesis of ketone 16 from the alpha-alkyloxy amide moiety in oxocene 5.,10.1021/ja035538u,2003-07-17,0.591158486750173
Journal of the American Chemical Society,Total Synthesis of the Phenylnaphthacenoid Type II Polyketide Antibiotic Formicamycin H via Regioselective Ruthenium-Catalyzed Hydrogen Auto-Transfer [4 + 2] Cycloaddition,"The first total synthesis of the pentacyclic phenylnaphthacenoid type II polyketide antibiotic formicamycin H is described. A key feature of the synthesis involves the convergent, regioselective assembly of the tetracyclic core via ruthenium-catalyzed α-ketol-benzocyclobutenone [4 + 2] cycloaddition. Double dehydration of the diol-containing cycloadduct provides an achiral enone, which upon asymmetric nucleophilic epoxidation and further manipulations delivers the penultimate tetracyclic trichloride in enantiomerically enriched form. Subsequent chemo- and atroposelective Suzuki cross-coupling of the tetracyclic trichloride introduces the E-ring to complete the total synthesis. Single-crystal X-ray diffraction analyses of two model compounds suggest that the initially assigned stereochemistry of the axially chiral C6-C7 linkage may require revision.",10.1021/jacs.4c09068,2024-09-12,0.5911571481754689
Journal of Organic Chemistry,Synthesis of the Bis-Spiroacetal Core of the Antimitotic Agent Spirastrellolide B,"The spirastrellolides are a family of potent antimitotic agents isolated from the marine sponge Spirastrella coccinea . Synthetic studies toward the DEF bis-spiroacetal core of spirastrellolide B are reported. A modular approach was pursued by the use of two dithiane disconnections to enable a highly convergent synthesis. The ease of lithiation and nucleophilicity of these 2-substituted-1,3-dithianes were investigated during the course of the synthesis, and the alkylations were found to proceed most efficiently at elevated temperatures. Formation of the [5,6,6]-bis-spiroacetal ring system was achieved via a double dithiane deprotection/spiroacetalization strategy.",10.1021/jo201729t,2011-10-13,0.5911529035288866
Organic Letters,Stereoselective Total Synthesis of Dihydrocorynantheol,"[reaction: see text] A stereoselective synthesis of the indole alkaloid dihydrocorynantheol (1) from indole-3-acetic acid has been achieved by a sequence involving 9 as a key intermediate. The synthesis of the unsaturated lactam ring in 9 highlights a series of catalytic organometallic reactions featuring two ring-closing metatheses and a zirconocene-catalyzed carbomagnesation. Since no protecting groups were used, the present synthesis of 1 is exceedingly concise, consisting of only eight distinct operations.",10.1021/ol026470a,2002-08-23,0.5911495178641483
Tetrahedron,Vinylsilyl Grignard reagents as aryne traps. A new route to (arylalkenyl)silanes.,,10.1016/s0040-4039(00)82473-9,1988-01-01,0.5911457697969176
Tetrahedron,The asymmetric synthesis of β-lactam antibiotics -II. The first enantioselective synthesis of the carbacephalosporin nucleus.,,10.1016/s0040-4039(00)89251-5,1985-01-01,0.5911382737415087
Journal of the American Chemical Society,Total Synthesis as a Vehicle for Collaboration,"“Collaboration” is not the first word most would associate with the field of total synthesis. In fact, the spirit of total synthesis is all-too-often reputed as being more competitive, rather than collaborative, sometimes even within individual laboratories. However, recent studies in total synthesis have inspired a number of collaborative efforts that strategically blend synthetic methodology, biocatalysis, biosynthesis, computational chemistry, and drug discovery with complex molecule synthesis. This Perspective highlights select recent advances in these areas, including collaborative syntheses of chlorolissoclimide, nigelladine A, artemisinin, ingenol, hippolachnin A, communesin A, and citrinalin B. The legendary Woodward–Eschenmoser collaboration that led to the total synthesis of vitamin B 12 is also discussed.",10.1021/jacs.9b05588,2019-07-29,0.5911375708292981
European Journal of Organic Chemistry,Synthesis of Diastereomeric 8‐Fluoro‐ABC‐Steroid Building Blocks,"Abstract An eight‐step linear sequence for the preparation of two diastereomers of an 8‐fluoro‐ABC‐steroid building block was developed. Key step was an intramolecular Diels–Alder reaction of an intermediate o ‐quinodimethane formed from a benzocyclobutene substituted with a 5‐fluorohex‐5‐en‐4‐one chain. This side chain was prepared from 6‐chlorohex‐1‐ene by bromofluorination, elimination of HBr, Finkelstein reaction and alkylation of a literature‐known benzocyclobutene derivative with the thus‐formed 6‐iodo‐2‐fluorohex‐1‐ene. Allylic oxidation of side chain's fluorovinyl moiety to an α‐fluoro‐α,β‐unsaturated ketone completed the preparation of the precursor for the [4+2]‐cycloaddition.",10.1002/ejoc.202300206,2023-03-22,0.5911324914264612
Synlett,New Synthesis of Azaheterocycles by Rearrangement of Isoxazoline-5-spirocycloalkane Compounds,"All articles of this category The thermal rearrangement of 5-spiro(cyclopropane or cyclobutane)isoxazolines and isoxazolidines has established a new methodology for the synthesis of selectively functionalised azaheterocycles. The application of the two-step process to the synthesis of heterocycles of different size is presented. The process is particularly convenient for the synthesis of N -bridgehead heterocycles, and its application to the synthesis of natural products bearing this skeleton is described. 1. Introduction 2. The Rearrangement 3. Monocyclic Products: Pyridine and Azepine Derivatives 4. N -Bridgehead Heterocycles 4.1. The Nitrile Oxide Route: Sequential Rearrangement-Annulation of Isoxazoline-5-spirocyclopropanes 4.2. The Nitrone Route: Use of Endocyclic Nitrones 5. Conclusion",10.1055/s-1993-22329,1993-01-01,0.5911296396041915
Synthesis,A Convenient Route to (<i>E</i>)-1-Alkenylsilanes via Isomerization of (<i>Z</i>)-1-Alkenylsilanes,,10.1055/s-1980-29211,1980-01-01,0.5911244413419938
Tetrahedron,A convenient route to carbocyclic analogs of nucleosides: (±) aristeromycin,,10.1016/s0040-4039(00)71394-3,1980-01-01,0.5911244413419938
Tetrahedron,"A convenient route to 1,3-cyclooctatetraenophanes",,10.1016/0040-4039(88)80011-x,1988-01-01,0.5911244413419938
Tetrahedron,"A convenient route to 4,4′-dialkoxyazoxybenzenes",,10.1016/s0040-4039(00)62013-0,1966-01-01,0.5911244413419938
Tetrahedron,A Convenient route to troponoids,,10.1016/s0040-4039(01)96043-5,1973-01-01,0.5911244413419938
Tetrahedron,A convenient route to unsymmetrical conjugated diynes,,10.1016/0040-4039(96)00414-5,1996-04-01,0.5911244413419938
Journal of the American Chemical Society,Total Synthesis of (+)-Amphidinolide A. Assembly of the Fragments,"The structure elucidation of (+)-amphidinolide A, a cytotoxic macrolide, has been accomplished by employing a combination of total synthesis and NMR spectroscopic analysis. Amphidinolide A possesses two skipped 1,4-diene subunits which are accessible by ruthenium-catalyzed alkene-alkyne couplings. Previous total syntheses had revealed that the reported structure was incorrect; therefore, to incorporate maximum flexibility into the synthesis, with the ultimate goal of determining the correct structure, a highly convergent approach was chosen. Furthermore, liberal use was made of catalytic asymmetric transformations to set individual stereocenters. Three different strategies were envisioned for the end game, and due to the highly convergent nature of the synthesis, all three routes disconnect to the same three key intermediates, 5, 6, and 7. Diastereomers of 6 and 7 were easily prepared by modification of the synthetic routes to allow access to multiple diastereomers of 1 for structural determination.",10.1021/ja0533646,2005-09-07,0.5911231684697531
Synlett,A Selective Photoaffinity Ligand for the Kainate Class of Excitatory Amino Acid Receptor,"All articles of this category The isopropenyl side chain of kainic acid (KA) has been replaced with a trifluoromethyldiazoketone group, resulting in a derivative (""diazoKA"") that gives efficient photo-induced crosslinking to the active site of the KA class of glutamate receptor. The incorporation of this functional group is accomplished via a simple, one step coupling of a carboxylic acid and 2,2,2-trifluorodiazoethane in a procedure that should be generally applicable to the preparation of other photoaffinity labels. Major advantages include excellent stability towards acidic conditions, even Boc and t-butyl ester deprotection, as well as a reduced tendency to undergo (non-productive) Wolff rearrangement after binding and irradiation. The observed crosslinking paves the way for identifying the active site residues of the KA receptor. kainic acid - trifluoromethyldiazoketone - photoaffinity ligand - trifluoromethyldiazomethane coupling - KA receptor",10.1055/s-1997-6129,1997-06-01,0.5911052480153508
Synthesis,An Efficient Synthesis of an NMDA Receptor Antagonist via Stereoselective Fluorination,"Herein is described the development and use of a novel bis(dialkylamino)sulfur difluoride reagent to effect the stereoselective conversion of a benzylic alcohol into a benzylic fluoride. A new method for the synthesis of 1H-pyrazolo[3,4-d]pyrimidin-4-amines is reported. Additionally, a practical method for the addition of a hindered alkoxide to an epoxide is demonstrated.",10.1055/s-2008-1032181,2008-03-01,0.5911020522498146
Synthesis,Enantioselective Synthesis of 2-Phenyl-9-oxabispidines,"A small selection of enantiomerically pure 2-phenyl-9-oxabispidines was synthesized in a three to five step procedure from commercially available starting materials. Ring opening of (R,R)-3-phenylglycidol with benzylamine, condensation with (S)-epichlorohydrin to the corresponding cis-2,6-bis(hydroxymethyl)-substituted morpholine intermediate, and final cyclization with a primary amine delivered the desired 2-phenyl-9-oxabispidines in good yields. The substituents at the nitrogen atoms were varied by de­benzylation and subsequent alkylation.",10.1055/s-2007-966040,2007-05-24,0.5910997347209056
Journal of Organic Chemistry,Synthesis of 1-Deoxy-<scp>d</scp>-galactohomonojirimycin via Enantiomerically Pure Allenylstannanes,1-Deoxy-D-galactohomonojirimycin was synthesized in seven steps from optically pure allenylstannane 4 and L-lactate-derived aldehyde 5 in 48% overall yield. The key step was the Lewis acid catalyzed reaction of 4 and 5 to give the syn-amino alcohol in excellent yield and very high diastereoselectivity.,10.1021/jo0303012,2003-12-12,0.5910988002877076
Tetrahedron,Toward the total synthesis of pseudolaric acid B. Preparation of a key intermediate by degradation and its use in the reassembly of the natural product,,10.1016/s0040-4039(02)00596-8,2002-05-01,0.5910897884208339
Organic Process Research & Development,"Scalable and Cost-Effective Synthetic Process for the Preparation of <scp>l</scp>-3,4-Dihydroxyphenylalanine─Levodopa","We reported the development of a novel synthetic process for Levodopa (1), which involves two simple chemical steps. The first step includes the reaction of l -tyrosine (18) with aqueous hydrogen bromide (HBr) to yield 3-bromo- l -tyrosine (19). The second step involves hydroxylation using an alkali base and copper iodide as a catalyst to produce Levodopa (1) with good quality and an overall yield of 41.75%. This new synthetic approach offers several advantages, including good reactivity, low cost, mitigation of the poor solubility issues associated with the reported process, and finally, it is industrially viable and capable of controlling the quality of the final Levodopa drug substance.",10.1021/acs.oprd.3c00313,2023-12-29,0.5910869220216799
Tetrahedron,A synthesis of the naphthalene core of streptovaricin D via A synthon of NH2+,,10.1016/s0040-4039(00)81382-9,1983-01-01,0.5910826502710205
Tetrahedron,Synthesis of the C1C9 core of bengazole A: Harnessing the ambident nucleophilicity of 2-lithiooxazole,,10.1016/s0040-4039(98)00494-8,1998-05-01,0.5910826502710205
Tetrahedron,The synthesis of spirophanes from a pentaerythrityl core,,10.1016/j.tetlet.2005.01.085,2005-02-05,0.5910826502710205
Tetrahedron,Synthesis of streptorubin B core,,10.1016/j.tetlet.2005.09.024,2005-09-22,0.5910826502710205
Tetrahedron,Synthesis of a tricyclic core of rameswaralide,,10.1016/j.tetlet.2010.09.042,2010-09-27,0.5910826502710205
Tetrahedron,Synthesis of adenylyl-(2′→5′)-adenylyl-(2′→5′)-adenosine (2-5A core),,10.1016/0040-4039(80)88081-6,1980-01-01,0.5910826502710205
Tetrahedron,Synthesis of the macrolide core of migrastatin,,10.1016/s0040-4039(02)02281-5,2002-12-01,0.5910826502710205
Tetrahedron,Synthesis of the pentacyclic core of lihouidine,,10.1016/j.tetlet.2008.01.118,2008-02-02,0.5910826502710205
Tetrahedron,Synthesis of the diazatricyclic core of the marine alkaloids madangamines,,10.1016/j.tetlet.2004.06.103,2004-07-21,0.5910826502710205
Tetrahedron,Synthesis of the tetracyclic core of the bisabosquals,,10.1016/j.tetlet.2004.05.005,2004-05-29,0.5910826502710205
Tetrahedron,Reprint of: Synthesis of a tricyclic core of rameswaralide,,10.1016/j.tetlet.2011.03.001,2011-03-16,0.5910826502710205
Tetrahedron,Synthesis of (+)-epicolidine C and the 6/6/6/5 tetracyclic core of spylidone,,10.1016/j.tetlet.2024.155181,2024-07-05,0.5910826502710205
Tetrahedron,Synthesis of the tetracyclic core of the bisabosquals,,10.1016/s0040-4039(04)01026-3,2004-05-01,0.5910826502710205
Tetrahedron,Stereocontrolled synthesis of the macrolactone core of neopeltolide,,10.1016/j.tetlet.2018.12.066,2018-12-28,0.5910826502710205
Tetrahedron,Synthesis of a monocyclic core of the antifungal sordarins,,10.1016/s0040-4039(98)01910-8,1998-11-01,0.5910826502710205
Journal of the American Chemical Society,Evolution of a Synthetic Strategy for Complex Polypyrrole Alkaloids: Total Syntheses of Curvulamine and Curindolizine,"Structurally unprecedented antibacterial alkaloids containing multiple electron-rich pyrrole units have recently been isolated from Curvularia sp. and Bipolaris maydis fungi. This article documents the evolution of a synthetic program aimed at accessing the flagship metabolites curvulamine and curindolizine which are presumably a dimer and trimer of a C 10 N biosynthetic building block, respectively. Starting with curvulamine, we detail several strategies to merge two simple, bioinspired fragments, which while ultimately unsuccessful, led us toward a pyrroloazepinone building block-based strategy and an improved synthesis of this 10π-aromatic heterocycle. A two-step annulation process was then designed to forge a conserved tetracyclic bis-pyrrole architecture and advanced into a variety of late-stage intermediates; unfortunately, however, a failed decarboxylation thwarted the total synthesis of curvulamine. By tailoring our annulation precursors, success was ultimately found through the use of a cyanohydrin nucleophile which enabled a 10-step total synthesis of curvulamine. Attempts were then made to realize a biomimetic coupling of curvulamine with an additional C 10 N fragment to arrive at curindolizine, the most complex family member. Although unproductive, we developed a 14-step total synthesis of this alkaloid through an abiotic coupling approach. Throughout this work, effort was made to harness and exploit the innate reactivity of the pyrrole nucleus, an objective which has uncovered many interesting findings in the chemistry of this reactive heterocycle.",10.1021/jacs.0c13465,2021-02-11,0.5910781716245379
Organic Letters,"Stereocontrolled Generation of the (2<i>R</i>) Chroman Core of Vitamin E: Total Synthesis of (2<i>R</i>,4′<i>RS</i>,8′<i>RS</i>)-α-Tocopherol","(2R,4'RS,8'RS)-alpha-tocopherol (1) was prepared using, as the two key steps, a novel diastereoselective TiCl(4)-promoted (S)-sulfoxide-directed allylation of ketal 2 with allyl trimethyl silane 3 to efficiently generate the challenging (2R) stereocenter of the chroman moiety and a cross-metathesis reaction with olefin 4 to efficiently join the lipophilic alkyl chain present in the final target.",10.1021/ol9020783,2009-09-30,0.5910713803420212
Tetrahedron,"An efficient chiral synthesis of fluoro-containing amino acids: N-benzyloxycarbonyl-2-amino-4,4-difluorobutyric acid methyl ester and its analogs",,10.1016/j.tetlet.2007.11.163,2007-12-05,0.5910687819900817
Organic Letters,Formal Syntheses of Naturally Occurring Welwitindolinones,"The formal syntheses of N-methylwelwitindolinone C isothiocyanate, N-methylwelwitindolinone C isonitrile, N-methylwelwitindolinone D isonitrile, 3-hydroxy-N-methylwelwitindolinone C isothiocyanate, and 3-hydroxy-N-methylwelwitindolinone C isonitrile are reported. The synthesis features several novel processes, including a Lewis acid mediated coupling between a benzylic-type heteroaromatic alcohol and a highly functionalized silyl ketene acetal, an intramolecular enolate arylation, and a regioselective, Pd(0)-catalyzed π-allylic cyclization of a γ-benzoyloxy enone moiety that is revealed by unmasking a furan ring.",10.1021/ol301424h,2012-07-25,0.5910663579937271
Angewandte Chemie International Edition,Total Synthesis of Shearinines D and G: A Convergent Approach to Indole Diterpenoids,"The first total syntheses of the indole diterpenoids (+)-shearinine G and D are disclosed. The successful routes rely on late-stage coupling of two complex fragments. Formation of the challenging trans-hydrindane motif was accomplished by diastereoselective, intramolecular cyclopropanation. A one-pot sequence consisting of Sharpless dihydroxylation/Achmatowicz reaction was developed to install the dioxabicyclo[3.2.1]octane motif. The indenone subunit was accessed by Prins cyclization. Tuning the electronic nature of the substituents on the parent arylcarboxaldehyde allowed access to divergent products that were further transformed into shearinines G and D. Riley-type oxidation of a bicyclic enone yielded a surprising stereochemical outcome.",10.1002/anie.202112838,2021-11-05,0.5910656852626394
European Journal of Organic Chemistry,Asymmetric Synthesis of Concentricolide,"Abstract A practical strategy for the synthesis of both (–)‐ and (+)‐concentricolide from salicylic acid has been developed. The key feature of the approach is sequential aromatic lithiation and condensation with an aldehyde directed by a chiral oxazoline unit derived either from L ‐ or D ‐phenylalaninol, which is employed as an auxiliary.",10.1002/ejoc.201403604,2015-02-18,0.5910645075780357
Journal of Organic Chemistry,Asymmetric Catalytic Access to Piperazin-2-ones and Morpholin-2-ones in a One-Pot Approach: Rapid Synthesis of an Intermediate to Aprepitant,"A one-pot Knoevenagel reaction/asymmetric epoxidation/domino ring-opening cyclization (DROC) has been developed from commercial aldehydes, (phenylsulfonyl)acetonitrile, cumyl hydroperoxide, 1,2-ethylendiamines, and 1,2-ethanol amines to provide 3-aryl/alkyl piperazin-2-ones and morpholin-2-ones in yields of 38 to 90% and up to 99% ee. Two out of the three steps are stereoselectively catalyzed by a quinine derived urea. The sequence has been applied for a short enantioselective entry to a key intermediate, in both absolute configurations, involved in the synthesis of the potent antiemetic drug Aprepitant.",10.1021/acs.joc.2c02491,2023-02-21,0.5910612970752009
Tetrahedron,Synthesis of branched-chain nitro and amino sugars via the nitromethane synthesis,,10.1016/s0040-4039(01)88592-0,1969-01-01,0.5910604704690791
Tetrahedron,A short synthesis of the β-amyloid (Aβ) aggregation inhibitor 3-p-Toluoyl-2-[4′-(3-diethylaminopropoxy)-phenyl]-benzofuran,,10.1016/s0040-4039(99)02030-4,1999-12-01,0.5910543049802808
Tetrahedron,An approach to erythrophleum alkaloids. Synthesis of methyl (−)-4-epi-cassamate,,10.1016/s0040-4039(00)84778-4,1986-01-01,0.5910508649252519
Angewandte Chemie International Edition,Enantioselective Total Synthesis of Angucyclinone-Type Antibiotics Rubiginones A2 and C2,"The tetracyclic skeleton of C4-oxygenated angucyclinone-type antibiotics rubiginones A2 ((+)-3) and C2 ((−)-4) is constructed by Diels–Alder reaction of a racemic sulfinyl-substituted methyl juglone and the enantiopure vinyl cyclohexene 2, which is prepared in nine steps and in 26 % overall yield from sulfinyl-substituted p-quinol 1. TBDMS=tert-butyldimethylsilyl.",10.1002/1521-3773(20020802)41:15<2755::aid-anie2755>3.0.co;2-a,2002-08-02,0.5910465224516019
Journal of Organic Chemistry,"A Highly Abbreviated Synthesis of Dibenzo[<i>def,p</i>]chrysene and Its 12-Methoxy Derivative, a Key Precursor for the Synthesis of the Proximate and Ultimate Carcinogens of Dibenzo[<i>def,p</i>]chrysene","Dibenzo[def,p]chrysene (DBC) (1), is by far the most mutagenic and toxic polycyclic aromatic hydrocarbon identified. Its metabolic activation leads to trans-11,12-dihydroxy-11,12-dihydro-DBC (2), which is further metabolized to the ultimate metabolite, anti-trans-11,12-dihydroxy-13,14-epoxy-11,12,13,14-tetrahydro-DBC (3), that binds to DNA causing mutations and ultimately tumor induction. We report a facile route for the syntheses of DBC (1) and its 12-methoxy derivative (12-methoxy-DBC) (13), a key intermediate for the synthesis of 2 and 3, using a Suzuki cross-coupling approach.",10.1021/jo0303822,2004-04-28,0.5910456973828115
Tetrahedron,"Structure and synthesis of a derivative of fasciculiferin, a novel peltogynoid from Acacia fasciculifera",,10.1016/s0040-4039(01)86634-x,1979-01-01,0.5910375632817262
Tetrahedron,Palladium-catalyzed carbonylative coupling of α-chloroketones with hydrazines: a simple route to pyrazolone derivatives,,10.1016/j.tetlet.2016.06.072,2016-06-25,0.5910370237307428
Synthesis,Annulations via Bifunctional Reagents. Total Syntheses of (±)-Methyl Cantabrenonate and (±)-Methyl Epoxycantabronate,"All articles of this category Total syntheses of the angularly fused triquinane sesquiterpenoids (±)-methyl cantabrenonate (10) and (±)-methyl epoxycantabronate (11) are described. The bicyclic enone, ( RS )-5-methylbicyclo-[3.3.0]oct-1 (8)-en-2-one (18) , was readily obtained from 3-methyl-2-cyclopenten-1-one (20) . The highly stereoselective conversion of 18 into the tricyclic oxo alkene, (1 R *,5 R *,8 R *)-5-methyl-9-methylenetricyclo [6.3.0.0 1,5 ]undecan-2-one (19) , was achieved via a one-pot process involving the reaction of 18 with the novel lower order bifunctional cuprate reagent lithium (4-chloro-1-buten-2-yl)-cyanocuprate (15) . The key intermediate 19 was transformed into the tricyclic enone (1 R *,5 R *,8 S *, 9 R *)-2,5,9-trimethyltricyclo-[6.3.0.0 1,5 ]undec-2-en-4-one (44) , by means of a straightforward sequence of reactions. Hydrogenation of 44 gave a single ketone 45 , which was converted, in two synthetic operations, into (±)- 10 . Treatment of 10 with hydrogen peroxide/sodium hydroxide provided, stereoselectively, (±)- 11 .",10.1055/s-1992-34160,1992-01-01,0.5910350589109407
Tetrahedron,Synthesis of 2-azidoethyl α-d-mannopyranoside orthogonally protected and selective deprotections,,10.1016/j.tetlet.2006.02.063,2006-03-01,0.5910295100005667
Organic Letters,Selective Synthesis of Pyrazolonyl Spirodihydroquinolines or Pyrazolonyl Spiroindolines under Aerobic or Anaerobic Conditions,"Presented herein is a condition-controlled selective synthesis of pyrazolonyl spirodihydroquinolines or pyrazolonyl spiroindolines through formal [5 + 1] or [4 + 1] spiroannulation of 2-alkenylanilines with diazopyrazolones. Mechanistically, the formation of the title products involves initial generation of a pyrazolonyl spiro-fused seven-membered ruthenacycle species serving as a key intermediate through Ru(II)-catalyzed C–H/N–H bonds metalation, carbene formation, and its migratory insertion. When the reaction is carried out under air, the key intermediate undergoes reductive elimination to afford spirodihydroquinoline. When the reaction is run under argon, the key intermediate undergoes protonation and intramolecular nucleophilic addition to furnish spiroindoline. This work provides an atom-economical protocol for the effective functionalization of alkenyl C(sp 2 )–H bond, allowing rapid and selective assembly of valuable spiroscaffolds with a broad range of substrates.",10.1021/acs.orglett.2c03952,2022-12-16,0.5910241290833055
European Journal of Organic Chemistry,Regioselective Formal Hydroamidation of Alkynes: Synthesis of α‐Substituted Acrylamides,"Abstract The formal hydroamidation of alkyne is a powerful synthetic method that enables the formation of various α,β‐unsaturated amides. In this article, the efficient formal hydroamidation of terminal and internal alkynes is described, which constitutes the Ni‐catalyzed α‐selective hydroalumination of alkynes and subsequent treatment with isocyanates. This method is gram‐scalable and the synthetic utility is highlighted by the synthesis of a β‐lactam from α‐phenyl acrylamide.",10.1002/ejoc.202401484,2025-02-14,0.5910227793642729
Synlett,"Palladium-Catalysed Coupling of 4-Halopyrrolo[2,3-<i>d</i>]pyrimidines with Arylacetylenes: Synthesis of a New Heterocyclic System - 4<i>H</i>-Pyrrolo[2,3,4-<i>de</i>]pyrimido[5′,4′:5,6][1,3]diazepino[1,7-<i>a</i>]indole","Palladium-catalysed reaction of methyl 5-amino-4-chloro(or iodo)-7-methyl-2-methylthiopyrrolo[2,3-d]pyrimidine-6-carboxylate with arylacetylenes affords the corresponding 4-(arylethynyl)pyrrolopyrimidines. Reaction of 5-amino-4-iodopyrrolopyrimidine with 2-ethynyl-N-mesylaniline in the presence of PdCl2(PPh3)2 and CuI led to the formation of 5-amino-4-(1-mesylindol-2-yl)pyrrolopyrimidine which after the removing of mesyl group cyclised with ethyl orthoformate to give the first representative of a novel heterocycle - 4H-pyrrolo[2,3,4-de]pyrimido[5′,4′:5,6][1,3]diazepino[1,7-a]indole.",10.1055/s-2004-832820,2004-01-01,0.5910215545241219
Synthesis,"Diastereoselective Synthesis of 2,5-Disubstituted Decahydroquinolines via Ring-Rearrangement Metathesis and Zirconium-Mediated Cyclization","A diastereoselective approach to 2,5-substituted decahydroquinolines by zirconium-mediated cyclization of unsaturated α,α′-disubstituted piperidines II is described. The required piperidines could be obtained from secondary sulfonamides III via ruthenium-catalyzed ring-rearrangement metathesis (RRM) in high yields. Racemic trans-195A and 2-epi-trans-195A were synthesized in 8 steps starting with butyraldehyde and cyclohex-2-enol.",10.1055/s-2004-834904,2004-01-01,0.5910205156751814
Angewandte Chemie International Edition,Total Synthesis of Diterpenoid Steenkrotin A,"A concise and diastereoselective total synthesis of the diterpenoid (±)-steenkrotin A is described for the first time. The strategy mainly features three key ring formations: 1) a rhodium-catalyzed O-H bond insertion followed by an intramolecular carbonyl-ene reaction to build up the tetrahydrofuran subunit; 2) sequential SmI2 -mediated Ueno-Stork and ketyl-olefin cyclizations to construct the [5,7] spirobicyclic skeleton; and 3) an intramolecular aldol condensation/vinylogous retro-aldol/aldol sequence to form the final six-membered ring with inversion of the relative configuration at the C7 position.",10.1002/anie.201502034,2015-04-17,0.5910157525498003
Organic Process Research & Development,Improved and Efficient Process for the Production of Highly Pure Iloperidone: A Psychotropic Agent,"The present work describes an improved and highly efficient process for the synthesis of iloperidone ( 1 ), an antipsychotic agent, which is free from potential impurities. The synthesis comprises N -alkylation of 1-(4-(3-chloropropoxy)-3-methoxyphenyl)ethanone ( 4 ) with 6-fluoro-3-piperidin-4-yl-1,2-benzisoxazole hydrochloride ( 5 ) in a mixture of water and heptane as solvent and sodium hydroxide as a base in the presence of tetrabutylammonium bromide as a phase transfer catalyst to yield iloperidone ( 1 ) with a yield of around 95% and a purity of 99.80% by HPLC. The present work also describes the optimization details performed to achieve the process attributes responsible for high yield and purity.",10.1021/op400335p,2014-01-06,0.5910126326996608
Journal of the American Chemical Society,Enantioselective Total Synthesis of Ustiloxin D,"Ustiloxin D and phomopsin A are potent antimitotic agents that bind to tubulin and interfere with cellular microtubule function. A synthetic strategy has been developed to allow access to both of the natural products as well as a variety of variants of the ustiloxin and phomopsin family members in order to provide sufficient quantities for biological studies. Herein we report the enantioselective total synthesis of ustiloxin D using a longest linear sequence of 20 steps. Four of the five stereocenters were set using catalytic asymmetric methodologies. In particular, Evans's new Al-catalyzed asymmetric aldol reaction facilitated access to both syn and anti products corresponding to the different benzylic stereochemistries found in ustiloxins and phomopsins. In addition, due to its high functional group tolerance, Trost's Pd-mediated etherification was used to construct the chiral tertiary alkyl-aryl ether. Taken together, these synthetic strategies allow us to use densely functionalized intermediates to realize an efficient synthesis of ustiloxin D.",10.1021/ja035429f,2003-05-14,0.5910065924737073
Tetrahedron,Efficient synthesis and X-ray structures of new α-quinolin-3-yl-α-aminonitriles and derivatives,,10.1016/j.tetlet.2012.11.032,2012-11-19,0.5910048648850645
Journal of the American Chemical Society,Cobalt-Catalyzed Regioselective Synthesis of Pyrrolidinone Derivatives by Reductive Coupling of Nitriles and Acrylamides,"A convenient and highly regioselective method for the synthesis of 5-methylenepyrrolidinone derivatives from various nitriles and acrylamides via a cobalt-catalyzed reductive coupling reaction is described. A possible mechanism that involves the formation of a cobaltaazacyclopentene intermediate from nitrile and acrylamide, protonation, keto-amide cyclization, and dehydration is proposed.",10.1021/ja9088296,2009-12-03,0.591004352952289
Synlett,Asymmetric Synthesis of Piperidines and Octahydroindolizines,"The conjugate addition of a homochiral lithium amide to a ξ-hydroxy-α,β-unsaturated ester, followed by a one-pot, ring-closure-N-debenzylation protocol has been used in the asymmetric syntheses of (S)-coniine and (R)-δ-coniceine (isolated as the corresponding hydrochloride salts) and the bicyclic core of stellettamide A. © Georg Thieme Verlag Stuttgart.",10.1055/s-0029-1219346,2010-01-25,0.5909992955172644
Journal of Organic Chemistry,Addition of Ester Enolates to <i>N</i>-Alkyl-2-fluoropyridinium Salts:  Total Synthesis of (±)-20-Deoxycamptothecin and (+)-Camptothecin,"Several 4-substituted dihydropyridones or 2-pyridones have been prepared by nucleophilic addition of alpha-(methylsulfanyl)ester enolates to N-alkyl-2-fluoropyridinium salts, followed by acid hydrolysis or oxidation with concomitant hydrolysis, of the intermediate 2-fluoro-1,4-dihydropyridine adducts, respectively. Addition of the enolate derived from isopropyl alpha-(methylsulfanyl)butyrate to N-(quinolylmethyl)-2-fluoropyridinium triflate 21 followed by DDQ treatment gave pyridone 29, from which (+/-)-20-deoxycamptothecin (31), a known precursor of camptothecin, was synthesized by a radical cyclization-desulfurization, with subsequent elaboration of the lactone E ring by chemoselective reduction. A similar sequence starting from the enolate of a chiral 2-hydroxybutyric acid derivative (33) provides access to natural (+)-camptothecin (37).",10.1021/jo026173j,2002-09-25,0.5909947451331491
Synthesis,"A Convenient Synthesis of 2-(3-Methyl-2,5-dioxopyrrolidin-1-yl)benzoic Acid","A new procedure for the synthesis of 2-(3-methyl-2,5-dioxopyrrolidin-1yl)benzoic acid (3) is reported via hydrogenation of 2-(3-methyl-2,5-dihydropyrrol-1-yl)benzoic acid (9) that in turn is available from fusion of anthranilic acid with citraconic anhydride. This method provides cleaner material in higher overall yield than that obtained using previously reported methods.",10.1055/s-2003-38065,2003-01-01,0.5909882602404042
Journal of Organic Chemistry,Synthesis of Simplified Azasordarin Analogs as Potential Antifungal Agents,"A new series of simplified azasordarin analogs was synthesized using as key steps a Diels-Alder reaction to generate a highly substituted bicyclo[2.2.1]heptane core, followed by a subsequent nitrile alkylation. Several additional strategies were investigated for the generation of the key tertiary nitrile or aldehyde thought to be required for inhibition at the fungal protein eukaryotic elongation factor 2. This new series also features a morpholino glycone previously reported in semisynthetic sordarin derivatives with broad spectrum antifungal activity. Despite a lack of activity against Candida albicans for these early de novo analogs, the synthetic route reported here permits more comprehensive modifications of the bicyclic core and structure-activity relationship studies that were not heretofore possible.",10.1021/acs.joc.9b00296,2019-03-28,0.5909868628208395
Organic Letters,Total Synthesis of (±)-Marsupellins A and B via Acetoxymarsupellone Using an Intramolecular Reductive Cyclization of Epoxycyanohydrin Derivative with Cp<sub>2</sub>TiI,"The first total synthesis of C3- and C9-oxidized ent -longipinane-type sesquiterpenoids containing acetoxymarsupellone, marsupellins A and B, has been accomplished. This unique core common to C3- and C9-oxidized ent -longipinane-type sesquiterpenoids was constructed via a new intramolecular reductive cyclization reaction of an epoxycyanohydrin derivative using Cp 2 TiI.",10.1021/acs.orglett.9b02207,2019-07-16,0.5909837871098423
Journal of Organic Chemistry,Synthesis of a Spirocyclic Indoline Lactone,"Base-promoted cyclization of tert-butyl [2-(benzylideneamino)phenyl]acetate (13a) and subsequent C3-alkylation with allyl bromide affords 3-allyl-2-phenyl-2,3-dihydro-1H-indole-3-carboxylic acid, tert-butyl ester (15b) in high yield as a single diastereomer. This result is contrary to prior publications that describe failed cyclization of an analogous ethyl ester (ethyl [2-(4-methoxybenzylideneamino)phenyl]acetate) under strongly basic conditions. N-Acylation, olefin dihydroxylation, and tert-butyl ester cleavage affords the spirocyclic lactone 18 as a pair of diastereomers. Isolation and characterization of individual diastereomers 18a and 18b are described.",10.1021/jo0499569,2004-03-09,0.5909834004217209
Journal of Organic Chemistry,Asymmetric Chemoenzymatic Synthesis of Ramatroban Using Lipases and Oxidoreductases,"A chemoenzymatic asymmetric route for the preparation of enantiopure (R)-ramatroban has been developed for the first time. The action of lipases and oxidoreductases has been independently studied, and both were found as excellent biocatalysts for the production of adequate chiral intermediates under very mild reaction conditions. CAL-B efficiently catalyzed the resolution of (±)-2,3,4,9-tetrahydro-1H-carbazol-3-ol that was acylated with high stereocontrol. On the other hand, ADH-A mediated bioreduction of 4,9-dihydro-1H-carbazol-3(2H)-one provided an alternative access to the same enantiopure alcohol previously obtained through lipase-catalyzed resolution, a useful synthetic building block in the synthesis of ramatroban. Inversion of the absolute configuration of (S)-2,3,4,9-tetrahydro-1H-carbazol-3-ol has been identified as a key point in the synthetic route, optimizing this process to avoid racemization of the azide intermediate, finally yielding (R)-ramatroban in enantiopure form by the formation of the corresponding amine and the convenient functionalization of both exocyclic and indole nitrogen atoms.",10.1021/jo300552v,2012-04-19,0.5909751550183311
Organic Letters,A Concise Silylamine Approach to 2-Amino-3-hydroxy-indoles with Potent <i>in vivo</i> Antimalaria Activity,"The development of a concise strategy to access 2-amino-3-hydroxy-indoles, which are disclosed as novel antimalarials with potent in vivo activity, is reported. Starting from isatins the target compounds are synthesized in 2 steps and in good yields via oxoindole intermediates by employing tert-butyldimethylsilyl amine (TBDMSNH(2)) as previously unexplored ammonia equivalent.",10.1021/ol101566h,2010-08-18,0.5909668123428558
Angewandte Chemie International Edition,Total Synthesis of (−)‐Glaucocalyxin A,"Abstract A practically useful method for the formation of the highly oxygenated bicyclo[3.2.1]octane ring system through Mn(OAc) 3 ‐mediated radical cyclization of alkynyl ketones was developed, which opens up a new avenue for the total synthesis of a number of highly oxidized diterpenoids. Application of this method enabled the first total synthesis of (−)‐glaucocalyxin A. Other salient features of the synthesis include a highly enantioselective conjugate addition/acylation cascade reaction, a Yamamoto aldol reaction, and an intramolecular Diels–Alder reaction to assemble the A/B ring system.",10.1002/anie.202005932,2020-05-19,0.5909661843215019
Organic Letters,A Mild Procedure for the Lewis Acid-Catalyzed Ring-Opening of Activated Cyclopropanes with Amine Nucleophiles,The Lewis acid-catalyzed ring-opening of methyl 1-nitrocyclopropanecarboxylates with amine nucleophiles is described. The reaction proceeds at room temperature and with complete preservation of the enantiomeric purity from the electrophilic center of the cyclopropane to the acyclic product. The methodology was applied in an enantioselective synthesis of the dual serotonin/norepinephrine reuptake inhibitor (3R)-3-(1 H-indol-1-yl)- N-methyl-3-phenylpropan-1-amine.,10.1021/ol8009286,2008-06-04,0.5909659883896744
Tetrahedron,"Diastereocontrolled synthesis of an enantiopure 4,4-disubstituted cyclohex-2-en-ol: a new route to (+)-quebrachamine",,10.1016/s0040-4039(01)02075-5,2002-01-01,0.5909656614324815
Synlett,The Application of Vinamidinium Salt to the Synthesis of 3-Chloro-α-carbolines,"A convenient synthesis of 3-chloro-α-carbolines by the condensation of vinamidinium salt with 2-indolinones via two steps is reported. This protocol has the advantages of readily available starting materials, high yields and easy workup.",10.1055/s-0037-1609151,2018-02-26,0.59096002056803
Synthesis,A Formal Catalytic Asymmetric Synthesis of (+)-Biotin with Modified Cinchona Alkaloids,"A formal catalytic asymmetric synthesis of (+)-biotin was realized. The key steps involve a catalytic, highly enantioselective and quantitative desymmetrization of a meso cyclic anhydride followed by a one-pot chemoselective reduction to form the optically active lactone intermediate in the Goldberg-Sternbach (+)-biotin synthesis.",10.1055/s-2001-16748,2001-01-01,0.5909546082829978
Angewandte Chemie International Edition,"Towards the Total Synthesis of Saponaceolides: Synthesis of cis-2,4-Disubstituted 3,3-Dimethylmethylenecyclohexanes",,10.1002/(sici)1521-3773(19991216)38:24<3662::aid-anie3662>3.3.co;2-t,1999-12-16,0.5909518553544818
Synlett,Divergent Two-Step Total Synthesis of Sclerotioloid A and B,Abstract A two-step divergent total synthesis of the structurally unique N-propargylated alkaloids sclerotioloid A and B has been achieved. The synthesis relies on a robust aldol-propargylation domino reaction yielding the key divergent intermediate. Single-crystal X-ray structure studies of the natural product sclerotioloid A show that it exists as a helically chiral racemate in the solid state.,10.1055/a-2535-1219,2025-02-07,0.5909505055646569
Organic Letters,Highly Enantioselective Rhodium-Catalyzed Transfer Hydrogenation of Tetrasubstituted Olefins: Application toward the Synthesis of GPR40 Agonist MK-2305,A highly efficient enantioselective synthesis for the potent G-protein-coupled receptor 40 agonist MK-2305 was developed. The key tetrasubstituted olefin was prepared via a stereoselective Mukaiyama aldol reaction/elimination sequence. The highly enantioselective rhodium-catalyzed transfer hydrogenation of the tetrasubstituted olefin afforded the target compound MK-2305 in excellent optical and chemical purity. The key asymmetric transfer hydrogenation proceeds in excellent yields and enantioselectivities for a variety of substrates. The superior reactivity of the tethered catalysts was revealed by NMR studies.,10.1021/acs.orglett.2c01021,2022-04-25,0.5909457685105861
Organic Process Research & Development,"Process Development and Optimization for Production of a Potassium Ion Channel Blocker, ICA-17043","A scalable process for the manufacture of a potassium ion channel blocker was developed and optimized. Key features of the process include an optimized Grignard reaction, a direct cyanation of the intermediate trityl alcohol derivative, and an improved nitrile hydrolysis protocol, relative to the original acidic hydrolysis conditions, to generate the crude active pharmaceutical ingredient (API) with >95% HPLC purity. The Grignard and the cyanation reactions could be telescoped, resulting in an improved throughput compared to the original four-step process. An effective recrystallization of the API was also developed and the process scaled up to manufacture multiple batches at the pilot scale.",10.1021/op3000916,2012-07-19,0.5909411808637712
Tetrahedron,A highly selective method for the synthesis of phenylacetaldehyde,,10.1016/s0040-4039(00)80328-7,1988-01-01,0.5909367108162427
Organic Letters,Total Synthesis of (−)-Enigmazole B,"Total synthesis of (−)-enigmazole B was achieved for the first time. Highlights of the present synthesis include an olefin cross-metathesis and hemiacetalization/intramolecular oxa-Michael addition sequence for accessing an ( E )-configured enol tosylate, a Sonogashira cross-coupling to assemble all the carbon atoms of the target natural product, a remarkably chemo- and regioselective Au-catalyzed intramolecular alkyne hydroalkoxylation for the construction of the dihydropyran ring, and a Yamaguchi macrolactonization to close the 18-membered macrolactone skeleton.",10.1021/acs.orglett.3c03002,2023-10-05,0.5909340585616617
Journal of the American Chemical Society,Stereoselective Functionalization of Racemic Cyclopropylzinc Reagents via Enantiodivergent Relay Coupling,"Efficient construction of optically pure molecules from readily available starting materials in a simple manner is an ongoing goal in asymmetric synthesis. As a straightforward route, transition-metal-catalyzed enantioconvergent coupling between widely available secondary alkyl electrophiles and organometallic nucleophiles has emerged as a powerful strategy to construct chiral center(s). However, the scope of racemic secondary alkylmetallic nucleophiles for this coupling remains limited in specific substrates because of the difficulties in stereoselective formation of the key alkylmetal intermediates. Here, we report an enantiodivergent strategy to efficiently achieve an array of synthetically useful chiral cyclopropanes, including chiral fluoroalkylated cyclopropanes and enantiomerically enriched cyclopropanes with chiral side chains, from racemic cyclopropylzinc reagents. This strategy relies on a one-pot, two-step enantiodivergent relay coupling process of the racemic cis -cyclopropylzinc reagents with two different electrophiles, which involves kinetic resolution of racemic cis -cyclopropylzinc reagents through a nickel-catalyzed enantioselective coupling with alkyl electrophiles, followed by a stereospecific relay coupling of the remaining enantiomeric cyclopropylzinc reagent with various electrophiles, to produce two types of functionalized chiral cyclopropanes with opposite configurations on the cyclopropane ring. These chiral cyclopropanes are versatile synthons for diverse transformations, rendering this strategy effective for obtaining structurally diversified molecules of medicinal interest.",10.1021/jacs.0c04462,2020-06-12,0.590928759171145
Organic Letters,A Facile FeCl<sub>3</sub>/I<sub>2</sub>-Catalyzed Aerobic Oxidative Coupling Reaction: Synthesis of Tetrasubstituted Imidazoles from Amidines and Chalcones,"A facile and efficient route for the synthesis of tetrasubstituted imidazoles from amidines and chalcones via FeCl3/I2-catalyzed aerobic oxidative coupling has been developed. This new strategy is featured by high regioselectivity and yields, good functional group tolerance, and mild reaction conditions.",10.1021/acs.orglett.5b01854,2015-07-21,0.5909151869955684
Synlett,"Dearomatization of <i>N</i>-Phenyl-2,6-dialkylpiperidines: Practical Synthesis of (±)-Solenopsin A and (±)-Dihydropinidine","The fire ant venom alkaloid (±)-solenopsin A was prepared in 4 steps (34%) starting from the N-phenyl-2-undecyl piperidine (1c). The key step in this synthesis involved the dearomatization of the phenyl group of N-phenyl-2-methyl-6-undecyl-piperidine (9c), which was carried out under Birch conditions.",10.1055/s-2004-830884,2004-08-04,0.5909150155026055
Organic Letters,Six-Step Total Synthesis of Isohirsut-4-ene through [5+2+1] Cycloaddition and Transannular Epoxide–Alkene Cyclization,"A six-step total synthesis of isohirsut-4-ene with a 5/5/5 tricyclic core has been achieved. The synthesis features a Rh(I)-catalyzed [5+2+1] cycloaddition, a Corey-Chaykovsky reaction, and a transannular epoxide-alkene cyclization that afford the skeleton of the target molecule. This three-step strategy was further utilized to synthesize more 5/5/5 tricyclic analogues with one or two bridgehead quaternary centers.",10.1021/acs.orglett.1c04383,2022-02-10,0.5909079276009302
Organic Letters,Gold-Catalyzed Intramolecular Hydroamination of <i>o</i>-Alkynylbenzyl Carbamates: A Route to Chiral Fluorinated Isoindoline and Isoquinoline Derivatives,Enantiomerically pure fluorinated isoindoline and dihydroisoquinoline scaffolds have been prepared through a diastereoselective addition of fluorinated nucleophiles to Ellman's N-(tert-butanesulfinyl)imines followed by a sequence of Sonogashira cross-coupling/gold(I)-catalyzed cycloisomerization of the corresponding carbamate. A more favored 5-exo-dig mechanism was observed mainly due to an electronic effect of the fluorinated group.,10.1021/ol3035142,2013-01-29,0.5908945692075578
Tetrahedron,"Synthesis of enantiomerically pure 3-butene-1,2-diol derivatives via a sharpless asymmetric epoxidation route.",,10.1016/0040-4039(93)85026-s,1993-03-01,0.5908926989008122
Journal of Organic Chemistry,Formal Enantiospecific Synthesis of (+)-FR900482,"The enantiospecific synthesis of FK973, and thus a formal enantiospecific synthesis of the antitumor antibiotic (+)-FR900482, is reported. Addition of aniline 8 to chiral epoxide 9, prepared from l-vinylglycine, afforded amino alcohol 12. After protection of the aliphatic nitrogen with the 9-phenylfluoren-9-yl group, to preserve the acidic stereocenter from racemization, formation of the aziridine 14 and intramolecular condensation under basic conditions gave azocinone 15. Hydroxymethylation at the benzylic position was achieved by a process involving methylenation, epoxidation, and hydrogenolysis; the absolute stereochemistry of the resulting alcohol 23 was determined by X-ray crystallographic analysis. The hydroxyl group of 23 was carbamoylated, and the aromatic amine was deprotected electrochemically and then oxidized to give an unstable hydroxylamine that was immediately protected as acetate 26. Oxidation of 26 with DMP, followed by hydrazinolysis of the acetyl group led to spontaneous closure of the resulting N-hydroxyamino ketone to hemiketal 28, which can be considered as a fully protected precursor of FR900482 and derivatives. Acid treatment to remove the protecting groups and acetylation afforded the triacetate FK973.",10.1021/jo0206521,2002-11-26,0.5908907135494342
Synthesis,Synthesis of 3-exo-Aroylhexahydroindoles via Sequential Gold(I)-Catalyzed Claisen-Type Rearrangement–Epimerization Reactions of cis-4-[N-Tosyl-N-(3-arylprop-2-ynyl)amino]cyclohex-2-en-1-ols,"A two-step process for the synthesis of 3- exo -aroylhexahydroindoles is described. cis -4-[ N -Tosyl- N -(3-arylprop-2-ynyl)amino]cyclohex-2-en-1-ols were cycloisomerized with a catalytic amount of chloro(triphenylphosphine)gold(I)/silver(I) hexafluoroantimonate (AuPPh 3 Cl/AgSbF 6 ); subsequent base treatment of the crude mixture provided 3- exo -aroylhexahydroindoles in good yields and complete stereoselectivity. A key step involving a 9- endo -dig attack of the hydroxyl group onto the gold-activated alkyne is proposed. The resulting allyl vinyl ether intermediate underwent a gold-assisted [3,3]-sigmatropic rearrangement to form 3- exo -3-aroylhexahydroindole derivatives.",10.1055/s-0033-1339129,2014-06-02,0.5908904235038467
European Journal of Organic Chemistry,"An Asymmetric Tandem Conjugative Addition‐Intramolecular Cyclisation Process to Provide Functionalised 3,6‐Dihydropyrans and 4,5‐Epoxytetrahydropyrans","Abstract The synthesis of 3,6‐dihydropyrans and 4,5‐epoxytetrahydropyrans starting from enantiomerically pure β‐hydroxy aldehyde (prepared by an organocatalytic aldol reaction) is described. The key step is a tandem sequence, which consists of a base‐promoted conjugative addition to a vinyl onium salt, followed by either an intramolecular Wittig process to provide 3,6‐dihydropyran derivatives or an intramolecular cyclisation/epoxidation process to afford 4,5‐epoxytetrahydropyran scaffolds. The products obtained by this method are common substructures in polyketide natural products.",10.1002/ejoc.200901145,2009-11-20,0.5908893320742865
Synthesis,Synthesis of New Benzocyclobutene Derivatives and Attempts to Prepare Benzocyclobutadiene,,10.1055/s-1970-21581,1970-01-01,0.5908867950301615
Synthesis,Total Synthesis of the Natural Pyridocoumarins Goniothaline A and B,"In this paper, we report the first total synthesis of goniothaline A and B, which are rare natural pyridocoumarins isolated from Goniothalamus australis. The key feature of the synthesis of goniothaline A is high-yielding silver-catalyzed cycloisomerization to afford the pyridine moiety. In addition, goniothaline B, a natural 8-hydroxyquinoline derivative, is readily synthesized by the regioselective demethylation of goniothaline A.",10.1055/s-0037-1610909,2018-09-17,0.5908862756473214
Synthesis,A Synthesis of the Pseudopterosin A-F Aglycone,The synthesis of the pseudopterosin A–F aglycone from 3-methylcatechol features (a) the use of asymmetric Ireland–Claisen and aryl Claisen rearrangements to install three of the four stereocentres present in the molecule and (b) an A→AB→ABC annulation strategy using ring-closing metathesis and cationic cyclisation reactions as the key steps.,10.1055/s-0032-1316643,2012-08-08,0.5908827138017421
Tetrahedron,"A short route to 3-alkynyl-4-bromo(chloro)cinnolines by Richter-type cyclization of ortho-(dodeca-1,3-diynyl)aryltriaz-1-enes",,10.1016/j.tetlet.2009.08.103,2009-09-03,0.5908822997176555
Synlett,"Stereocontrolled Synthesis of Sulfonyl 2,5-Diaryltetrahydrofurans","BF 3 ·OEt 2 -mediated stereocontrolled annulation of 4-alkenols affords sulfonyl 2,5-diaryltetrahydrofurans in good yields. The key synthetic route combines the facile stereoselective reduction of α-styryl-β-ketosulfones and an intramolecular Friedel–Crafts electrophilic cyclization of the resulting 4-alkenols. A plausible mechanism has been studied and proposed.",10.1055/s-0035-1560423,2016-03-04,0.590875810977478
Synlett,"2,3-Dihydropyridin-4(1H)-ones and 3-Aminocyclohex-2-enones: Synthesis, Functionalization, and Applications to Alkaloid Synthesis","This account summarizes our recent investigations into the chemistry of 2,3-dihydropyridin-4(1 H )-ones and 3-aminocyclohex-2-enones (enaminones). These enaminones are exceptionally versatile chemical scaffolds that serve as valuable intermediates in the synthesis of indolizidine and quinolizidine alkaloids and other bioactive compounds. Since we reported our first method for constructing enaminones in 2006, we have developed a number of additional approaches to the synthesis and derivatization of enaminones and we have explored their applications in natural product synthesis. 1 Background 2 Ynone Cyclization 2.1 Initial Discovery 2.2 Optimization of Reaction Conditions 2.3 Scope and Limitations 2.4 Mechanistic Studies 2.4 Application to Quinolone Synthesis 2.6 N -Butoxycarbonyl β-Lactam Approach 2.7 Synthesis of 3,4-Dihydro-1,2-oxazepin-5(2 H )-ones and Their Conversion into Enaminones 3 Ketene Cyclization 3.1 Chiral-Pool Approach 3.2 Three-Component Synthesis 4 C5 Functionalization 4.1 Suzuki Coupling of Iodoenaminones 4.2 Suzuki-Type Direct Cross-Coupling 4.3 Suzuki-Type Direct Cross-Coupling with Arylboronic ­Acids 4.4 Hiyama-Type Direct Cross-Coupling 4.5 Direct Coupling with Aryl Iodides 4.6 Alkenylation by the Fujiwara–Moritani Reaction 4.7 Alkenylation of Uracils 4.8 Aerobic Alkenylation and its Application to the Synthesis of 1,3,5-Trisubstituted Benzenes 4.9 Lithium Perchlorate-Catalyzed Alkylation 5 Applications to Total Synthesis 5.1 Total Synthesis of (+)-Ipalbidine and (+)-Antofine 5.2 Total Synthesis of ( R )- and ( S )-Boehmeriasin A 5.3 Total Synthesis of Tylocrebrine and Related Phenanthropiperidines 6",10.1055/s-0034-1378529,2014-09-24,0.5908744005359805
Journal of Organic Chemistry,Conjugate Addition−Dipolar Cycloaddition Cascade for the Synthesis of Benzo[<i>a</i>]quinolizine and Indolo[<i>a</i>]quinolizine Scaffolds: Application to the Total Synthesis of (±)-Yohimbenone,"A highly efficient total synthesis of (+/-)-yohimbenone and a formal synthesis of (+/-)-emetine is described. The key element of the synthesis consists of a conjugate addition-dipolar cycloaddition of 2,3-bis(phenylsulfonyl)-1,3-butadiene with an appropriate oxime. The resulting cycloadducts are cleaved reductively to provide azapolycyclic scaffolds with strategically placed functionality for further manipulation to the target compounds.",10.1021/jo9003579,2009-04-01,0.590867140802659
Tetrahedron,Optimized synthesis of LNA uracil nucleosides,,10.1016/j.tetlet.2008.09.165,2008-10-03,0.5908600206152502
Tetrahedron,A novel one-pot synthesis of substituted 4-t-butyldimethylsilyloxy-thiazoles,,10.1016/s0040-4039(00)82109-7,1988-01-01,0.5908582117920752
Tetrahedron,Enantiospecific total synthesis of the enantiomer of the indole alkaloid intermediate macroline,,10.1016/s0040-4039(02)01729-x,2002-10-01,0.590857624807172
Journal of Organic Chemistry,Scope and Limitations of a New Highly Selective Synthesis of Unsymmetrical Monomers for the Synthesis of Precursors toward Poly(arylenevinylene)s,"In our laboratory a precursor route to poly(p-phenylenevinylene) derivatives is developed in which unsymmetrically substituted p-xylene derivatives, possessing a benzylic sulfinylalkyl group, are used as monomers. Because of this unsymmetry, we were forced to investigate thoroughly the synthesis of these sulfoxides, as we start from symmetric and readily accessible molecules, namely, bis(halomethyl)-p-xylene derivatives. In a former publication, a new extremely effective route for the production of these unsymmetrically substituted sulfinyl monomers was presented. This paper expands upon these previously reported results. To examine the scope and limitations of this elegant route, this new method was applied to the synthesis of various derivatives not included in the initial work.",10.1021/jo990111k,1999-12-29,0.5908522534210615
Angewandte Chemie International Edition,Biomimetic Synthesis of an Antiviral Cinnamoylphloroglucinol Collection from <i>Cleistocalyx operculatus</i>: A Synthetic Strategy Based on Biogenetic Building Blocks,"A synthetic strategy based on biogenetic building blocks for the collective and divergent biomimetic synthesis of cleistoperlones A-F, a cinnamoylphloroglucinol collection discovered from Cleistocalyx operculatus, has been developed. These syntheses proceeded successfully in only six to seven steps starting from commercially available 1,3,5-benzenetriol and involving oxidative activation of stable biogenetic building blocks as a crucial step. Key features of the syntheses include a unique Michael addition/ketalization/1,6-addition/enol-keto tautomerism cascade reaction for the construction of the dihydropyrano[3,2-d]xanthene tetracyclic core of cleistoperlones A and B, and a rare inverse-electron-demand hetero-Diels-Alder cycloaddition for the establishment of benzopyran ring in cleistoperlones D-F. Moreover, cleistoperlone A exhibited significant antiviral activity against acyclovir-resistant strains of herpes simplex virus type 1 (HSV-1/Blue and HSV-1/153).",10.1002/anie.202312568,2023-10-18,0.590838301562527
Tetrahedron,"Concerted and two-step conformational ring-flipping in [2.2] (3,3′,4,4′) biphenylophanes1",,10.1016/s0040-4039(01)86632-6,1979-01-01,0.5908332335116202
Tetrahedron,A one-step ring enlargement of a thiophene to a thiepin,,10.1016/s0040-4039(01)94124-3,1972-01-01,0.5908332335116202
Organic Letters,"A Flexible, Convergent Approach to Polycyclic Indole Structures: Formal Synthesis of (±)-Mersicarpine","The formal synthesis of (+/-)-mersicarpine was achieved using an intermolecular radical addition-radical cyclization cascade. This key reaction represents a flexible, convergent route to numerous polycyclic indole derivatives.",10.1021/ol900996k,2009-06-02,0.5908276429931589
Journal of the American Chemical Society,"A Direct, One Step Synthesis of Imidazoles from Imines and Acid Chlorides:  A Palladium Catalyzed Multicomponent Coupling Approach","A palladium-catalyzed one-step synthesis of imidazoles from imines and acid chlorides is described. A plausible mechanism for this multicomponent reaction is provided, which explains the selective incorporation of two different imines into the final product with perfect regiocontrol. Overall, this catalytic process provides a modular method to prepare imidazoles directly from building blocks that are all either commercially available or readily generated.",10.1021/ja060705m,2006-04-14,0.5908081200879362
Synthesis,An Improved Procedure for the Preparation of Substituted Thiazoles,"All articles of this category The reaction between 3-amino-3-(dialkylamino)propenenitriles 1 and sodium thiocyanate in presence of bromine, provides an efficient route for the synthesis of 2-amino-5-cyano-4-(dialkylamino)thiazoles 3 .",10.1055/s-1993-25827,1993-01-01,0.5908072545071901
Synthesis,Synthesis of an Advanced Fragment of (+)-Trienomycinol,"The synthesis of the fully functionalized eastern fragment of trienomycins A–F, ansamycin antibiotics is described. A key step involves a peptidic coupling between a sulfonyl aniline and an enantiopure carboxylic acid obtained by a completely diastereoselective reduction of a β-ketosulfoxide to generate the stereogenic carbinol. Studies on the coupling with the western part were also performed, giving access to an advanced fragment of trienomycinol.",10.1055/s-0035-1562735,2016-08-18,0.5908010787103436
Organic Letters,Asymmetric Total Synthesis of the Antimalarial Drug (+)-Mefloquine Hydrochloride via Chiral <i>N</i>-Amino Cyclic Carbamate Hydrazones,Mefloquine hydrochloride is an important antimalarial drug. It is currently manufactured and administered in racemic form; however there are indications regarding the biological activity of the two enantiomers that suggest the superiority of the (+)-form. The asymmetric total synthesis of the (+)-enantiomer of mefloquine hydrochloride is described. The key asymmetric transformation utilized is a novel asymmetric Darzens reaction of a chiral α-chloro-N-amino cyclic carbamate hydrazone derived from an N-amino cyclic carbamate (ACC) chiral auxiliary.,10.1021/ol2010193,2011-05-26,0.5908000774774677
European Journal of Organic Chemistry,Total Synthesis of (–)‐Fasicularin and (–)‐Lepadiformine A Based on Zn‐Mediated Allylation of Chiral <i>N</i>‐<i>tert</i>‐Butanesulfinyl Ketimine,"Abstract The stereoselective total synthesis of fasicularin ( 1 ) andlepadiformine A ( 2 ) is described, which features the utilization of a Zn‐mediated allylation of a chiral, aliphatic, N ‐ tert ‐butanesulfinyl ketimine to construct the amino‐substituted quaternary carbon center in good yield and with excellent diastereoselectivity. The azaspirocyclic scaffold was installed sequentially by a Sharpless dihydroxylation and an internal epoxide‐opening reaction, and this scaffold was further converted into common intermediate 5 . Removing the tosyl (Ts) protecting group of 5 and reductively aminating usingLuche's reagent completed the synthesis of (–)‐fasicularin ( 1 ), while reducing 5 using L ‐selectride, deprotecting the Ts group, and finishing with an intramolecular amino alcohol cyclocondensation completed the total synthesis of (–)‐lepadiformine A ( 2 ).",10.1002/ejoc.200901422,2010-02-09,0.5907989895334754
Angewandte Chemie International Edition,Enantioselective and Collective Syntheses of Xanthanolides Involving a Controllable Dyotropic Rearrangement of <i>cis</i>‐β‐Lactones,"Let's swap: a scalable, atom-economic, enantio-, and diastereoselective synthetic route to trisubstituted γ-butyrolactones based on a Wagner-Meerwein-type dyotropic rearrangement of cis-β-lactones is described. This methodology was applied in efficient and protecting-group-free formal syntheses and total syntheses of various xanthanolide natural products.",10.1002/anie.201202643,2012-06-04,0.5907964254676651
Synlett,Enantioselective Synthesis of the Aglycones of Pseudopterosin and <i>seco</i>-Pseudopterosin via a Common Synthetic Intermediate,All articles of this category pseudopterosin - enantioselective synthesis - benzylic stereocontrol - chiral arene-Cr(CO) 3 complexes,10.1055/s-1997-1012,1997-11-01,0.5907959163623274
Angewandte Chemie International Edition,Synthesis of Diverse Lactam Carboxamides Leading to the Discovery of a New Transcription‐Factor Inhibitor,"Diversity is the key: Skeletal diversity is a useful starting point in the search for compounds that modulate protein–biopolymer interactions. A library of 400 lactam carboxamides has been synthesized in a short synthetic sequence and a new compound that inhibits the interaction of a transcription factor (HOXA13) with its DNA target has been discovered, and inhibition of transcription is demonstrated in cells.",10.1002/anie.200700762,2007-06-14,0.5907863278385189
Journal of Organic Chemistry,Synthesis of 2‘-<i>O</i>-Methoxyethylguanosine Using a Novel Silicon-Based Protecting Group,"A short and efficient synthesis of 2'-O-methoxyethylguanosine (8) is described. Central to this strategy is the development of a novel silicon-based protecting group (MDPSCl(2), 2) used to protect the 3',5'-hydroxyl groups of the ribose. Silylation of guanosine with 2 proceeded with excellent regioselectivity and in 79% yield. Alkylation of the 2'-hydroxyl group of 6 proceeded with methoxyethyl bromide and NaHMDS and afforded compound 7 in 85% yield, without any noticeable cleavage of the silyl protecting group and without the need to protect the guanine base moiety. Finally, deprotection of 7 was achieved using TBAF and produced 8 in 97% yield.",10.1021/jo025970e,2002-09-27,0.5907821509350333
European Journal of Organic Chemistry,Total Synthesis of the Proposed Structure of Trocheliophorolide D,"Abstract The proposed structure of trocheliophorolide D was synthesized, and the NMR spectra of the synthetic compound proved to be inconsistent with those of the natural product. Our synthesis features the construction of the 2‐butenolide moiety by using an aldol strategy and assembly of the triyne system during the final stage of the synthesis.",10.1002/ejoc.201101209,2011-10-24,0.5907748216420831
Tetrahedron,A new approach to the synthesis of 2-amino-2-deoxyglycosides,,10.1016/s0040-4039(01)89472-7,1964-01-01,0.59077450086428
Synthesis,Catalytic Epoxypolyene Cyclization via Radicals: A Simple Total Synthesis of Sclareol Oxide and its 8-Epimer,A short synthesis of sclareol oxide from epoxyfarnesyl acetone in six steps is described. The strategy features a titanocene-catalyzed epoxypolyene cyclization for the construction of the carbocyclic core structure. The exo olefin formed during the termination of the cyclization is essential for the ensuing functional group modification that results in the preparation of the dihydropyran.,10.1055/s-2006-942406,2006-07-01,0.5907605894567645
European Journal of Organic Chemistry,"A Facile and Reliable Method for the Synthesis of Tetrabenzoporphyrin from 4,7‐Dihydroisoindole","Abstract A new route to tetrabenzoporphyrins from the closest possible precursor of the unstable isoindole was developed. A key feature of this route is a dramatic facilitation of thearomatization of annelated rings, which is the most serious bottleneck in previous syntheses of tetrabenzoporphyrins. The capabilities of the new method are illustrated by the synthesis of meso ‐tetraaryltetrabenzoporphyrins, as well as the first unambiguous synthesis and characterization of 5,15‐diphenyltetrabenzoporphyrin.(© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2007)",10.1002/ejoc.200700014,2007-06-05,0.5907597465248521
Synlett,The Total Synthesis of Mollanol A by a Convergent Strategy,"Abstract Here, we briefly highlight our 15-step total synthesis of mollanol A, the first isolated member of the mollane-type grayanoids, which relied on a convergent strategy. A Stille coupling and a vinylogous aldol reaction/intramolecular oxa-Michael addition sequence were used to assemble the two fragments that featured most of the important chiral centers and nearly all the essential oxidation states of the natural product. The bicyclo[3.2.1]octane fragment was synthesized by using an InCl3-catalyzed Conia–ene cyclization reaction. The challenging tetrasubstituted alkene was constructed through a 1,4-reduction of the conjugated alkenes at a late stage. 1 Introduction 2 Total Synthesis of Mollanol A 3 Conclusion",10.1055/a-2103-9925,2023-05-31,0.5907577042439132
Journal of Organic Chemistry,Relative and Absolute Configuration of Allohedycaryol. Enantiospecific Total Synthesis of Its Enantiomer,"The enantiomer of (+)-allohedycaryol, a germacrane alcohol isolated from giant fennel (Ferula communis L.), has been synthesized, thereby elucidating the relative and absolute stereochemistry of the natural product. The synthesis of (-)-allohedycaryol started from (+)-alpha-cyperone (5) which was available in relatively large quantities via alkylation of imine 7 derived from (+)-dihydrocarvone and (R)-(+)-1-phenylethylamine. In a number of steps 5 was converted into the mesylate 4with a regio- and stereoselective epoxidation as the key step. A Marshall fragmentation of 4 was used to prepare the trans,trans-cyclodeca-1,6-diene ring present in allohedycaryol. The conformation of synthetic (-)-allohedycaryol was elucidated via photochemical conversion into a bourbonane system. The synthesis of (-)-allohedycaryol also showed that natural (+)-allohedycaryol has the opposite absolute stereochemistry to that normally found in higher plants.",10.1021/jo9602534,1996-01-01,0.5907563193747385
Journal of Organic Chemistry,Total Synthesis of Dimethyl Sulfomycinamate,"Dimethyl sulfomycinamate (1), a methanolysis product from the natural antibiotic sulfomycin I, is synthesized in 11 steps (Scheme 19). The chemistry of various pyridine, thiazole, and oxazole heterocycles and their coupling reactions under palladium catalysis are examined. The key transformations in the synthesis are the selective palladium-catalyzed coupling reactions on doubly activated pyridine 62 and the condensation reaction between bromo ketone 69 and amide 28 to form the oxazole moiety 76. The first preparation of oxazole triflates is described, as are some of their chemical properties.",10.1021/jo960433d,1996-01-01,0.5907504967203107
Organic Letters,"CuI-Catalyzed Coupling of <i>gem</i>-Dibromovinylanilides and Sulfonamides: An Efficient Method for the Synthesis of 2-Amidoindoles and Indolo[1,2-<i>a</i>]quinazolines","A Cu(I)-catalyzed, intermolecular protocol for the synthesis of 2-amidoindoles and tetrahydroindolo[1,2-a]quinazolines in shorter time and high yields is reported. The key highlight of this disclosure is the formation of 2-amidoindole and tetrahydroindolo[1,2-a]quinazoline moieties directly from gem-dibromovinylanilides and sulfonamides in a one-pot fashion through the in situ formation of ynamides followed by a base-promoted intramolecular hydroamidation.",10.1021/ol403365t,2013-12-30,0.5907500345299507
Angewandte Chemie International Edition,"The Asymmetric Total Synthesis of (+)‐Cytotrienin A, an Ansamycin‐Type Anticancer Drug","A star-studded lineup: (+)-Cytotrienin A was the target of an asymmetric total synthesis featuring an enantioselective aldol reaction, α-aminoxylation, deoxygenation, and a ring-closing metathesis to form the 21-membered macrolactam. This first total synthesis confirms the relative and absolute confguration of the molecule.",10.1002/anie.200802079,2008-07-21,0.5907462224840311
Tetrahedron,Synthesis of chiral adenosine receptor recognition units via a sharpless asymmetric epoxidation procedure,,10.1016/s0040-4039(00)94634-3,1990-01-01,0.5907443657749298
Organic Letters,A Concise Total Synthesis of (±)-Alantrypinone by a Novel Hetero-Diels−Alder Reaction,[reaction: see text] An efficient total synthesis of (+/-)-alantrypinone (1) and its 17-epi isomer (17) has been accomplished employing a novel aza-Diels-Alder reaction as the key step. The reaction sequence comprises 8 steps starting from anthranilic acid and proceeds in 13.5% overall yield. An interesting anionic equilibration between 1 and its epimer 17 has also been discovered.,10.1021/ol030070l,2003-08-08,0.5907431611399366
Organic Letters,Total Synthesis and Determination of the Absolute Configuration of Parimycin,"The first total syntheses of (±)-parimycin and ( R )-parimycin were accomplished from O -methylnaphthazarin ( 6 ) in nine synthetic steps. Intermolecular Diels–Alder reaction of 6 with diene 7, cyclodehydrogenation catalyzed by iodine-dimethyl sulfoxide, and sodium dithionite reduction were the key steps. The absolute configuration of natural parimycin was determined to be S .",10.1021/acs.orglett.9b02999,2019-09-12,0.5907425260937451
Organic Letters,Diastereoselective Synthesis of Vicinal Tertiary Diols,"A strategy for the synthesis of differentiated vicinal tertiary diols is described. The key step is a high-yielding, diastereoselective LaCl3·2LiCl-mediated addition of a Grignard or organolithium reagent to ketone 2a. The reaction is believed to proceed via a 1,3-chelated intermediate. One of the adducts has been transformed into a functionalized cyclopentenone resembling the core structure of pactamycin.",10.1021/ol4005799,2013-04-10,0.590739910240376
Tetrahedron,"Facile one-step synthesis of 2,5-diketopiperazines",,10.1016/j.tetlet.2014.01.133,2014-02-05,0.590736572230115
Tetrahedron,A novel route to some tricarbonyliron bicyclo[3.2.2]nonadienyl tetrafluoroborates.,,10.1016/s0040-4039(00)89429-0,1970-01-01,0.5907353051571779
Angewandte Chemie International Edition,Concise Total Synthesis of Nannocystin A,"Nannocystin A, a structurally unique 21-membered macrocyclic depsipeptide with low nanomolar inhibitory activity against elongation factor 1A, was synthesized according to a strategy involving the vinylogous Mukaiyama aldol reaction, Sharpless epoxidation, olefin metathesis, the Mitsunobu reaction, and a palladium-catalyzed intramolecular Suzuki coupling of a highly complex cyclization substrate. The overall synthesis is efficient and paves the way for preparation of analogues for drug development efforts.",10.1002/anie.201606679,2016-09-16,0.5907344601353273
Organic Letters,Synthesis of the C1−C12 Fragment of Fostriecin,[reaction: see text] The synthesis of the C(1)-C(12) fragment of fostriecin was achieved from (S)-glycidol in 15 steps by using an enantioselective allytitanation reaction and a ring-closure metathesis as the key steps.,10.1021/ol016116x,2001-06-12,0.5907344588938743
Synthesis,Studies Towards The Synthesis of Tartrolons D and E,"Abstract A concise and stereoselective synthesis of a key fragment C3-C22 unit of tartrolons D and E is demonstrated. Three crucial fragments are combined to form the 20-carbon chain, which contains four stereogenic centers in the monomeric unit of both natural products. The crucial fragments were synthesized in highly enantioselective routes from commercial starting compounds in two, eight, and two steps, respectively, and coupled using palladium-catalyzed Sonogashira coupling and directed 1,5-asymmetric aldol reaction as key steps.",10.1055/a-2048-2662,2023-03-06,0.5907256809657294
Journal of Organic Chemistry,"Hydroformylation of Alkenylamines. Concise Approaches toward Piperidines, Quinolizidines, and Related Alkaloids","Linear hydroformylation of N-protected allyl- or homoallylamines (cyclohydrocarbonylation: CHC), followed by a reductive amination constitute the two key steps toward convenient routes to aza-heterocycles.",10.1021/jo101776y,2010-11-17,0.5907253671721381
Tetrahedron,Dimethyldioxirane oxidations: A new and efficient desulfurization of thiopyrimidine and thiopurine nucleosides.,,10.1016/s0040-4039(00)61566-6,1993-11-01,0.5907176617101779
Journal of the American Chemical Society,Total Synthesis of Ecteinascidin 743,"The total synthesis of ecteinascidin 743 (1), an extremely potent antitumor agent, has been accomplished. The synthesis features Ugi's 4CC reaction, intramolecular Heck reaction, phenol-aldehyde cyclization, and acid-induced intramolecular sulfide formation.",10.1021/ja026216d,2002-05-17,0.5907168121172165
Synlett,"The Synthesis of α-Pinene Derived C<sub>2</sub>Symmetric, Optically Active 1,2-Diols","All articles of this category The synthesis of C 2 symmetric, optically active diols 6 and 7 from α-pinene is described. The preparation involves the osmium tetroxide oxidation of alkene 5 , prepared in good yield by a McMurry coupling of aldehyde 4 .",10.1055/s-1992-21559,1992-01-01,0.5907130407700143
Journal of Organic Chemistry,"The Rearrangement Route to 3-Carboxy- and 3-Hydroxymethyl-2-azabicyclo[2.1.1]hexanes:  3,5-Methanoprolines","Improved stereocontrolled syntheses of 5-anti-hydroxy-3-exo-methoxycarbonyl-2-azabicyclo[2.1.1]hexanes have been effected from pyridine. The key step in the electrophilic addition-rearrangement of 2-azabicyclo[2.2.0]hex-5-ene precursors incorporates either a 3-endo-phenyl group, as an acid precursor, or a 3-endo-phenyldimethylsilylmethyl group, as a potential hydroxymethyl and acid precursor.",10.1021/jo0484171,2004-12-29,0.5907117063868261
Organic Process Research & Development,Tetrahydro-4<i>H</i>-pyran-4-one: From the Laboratory Scale to Pilot Plant Manufacture,This study describes our recent efforts to find an efficient and scalable route to tetrahydro-4 H -pyran-4-one using the commercially available starting materials. The route scouting work and the full development of an efficient access to the target are described. This work culminated in the preparation of above 20 kg of the title compound in our pilot plant facility.,10.1021/acs.oprd.1c00403,2021-12-29,0.5907109008436194
Organic Letters,Synthetic and Mechanistic Studies of the Retro-Claisen Rearrangement 4. An Application to the Total Synthesis of (+)-Laurenyne,[formula: see text] A novel asymmetric total synthesis of marine natural product (+)-Laurenyne has been achieved. The key elements of the strategy are the sequential metal ion-templated SN2' cyclization affording a highly functionalized chiral vinyl cyclobutane and a retro-Claisen rearrangement for the construction of an eight-membered ring ether.,10.1021/ol0267174,2002-09-27,0.5906997574418155
Organic Letters,"Exceedingly Concise and Elegant Synthesis of (+)-Paniculatine, (−)-Magellanine, and (+)-Magellaninone","Starting from inexpensive (+)-pulegone as the chiral building block, a highly convergent synthesis of the unusual diquinane-based structures of (+)-paniculatine (1), (-)-magellanine (2), and (+)-magellaninone (3), has been achieved. This approach is based upon a tandem acylation-alkylation of ketoester 8 and palladium-catalyzed olefin insertion, oxidation, and hydrogenation for construction of the tetracyclic framework. This exceedingly concise strategy, requiring only 12-14 steps, is the shortest to date.",10.1021/acs.orglett.5b01975,2015-07-24,0.5906996107974463
Tetrahedron,Synthesis of methyl-substituted trans-fused tetrahydropyrans via 6-endo cyclization,,10.1016/s0040-4039(99)01665-2,1999-11-01,0.5906991082837071
Journal of Organic Chemistry,"Efficient Pyridinylmethyl Functionalization:  Synthesis of 10,10-Bis[(2-fluoro-4-pyridinyl)methyl]-9(10<i>H</i>)-anthracenone (DMP 543), an Acetylcholine Release Enhancing Agent","2-Fluoro-4-methylpyridine (3) is efficiently functionalized by chlorination, hydrolysis and methanesulfonylation into the novel alkylating agent 7. This mesylate is used for the bisalkylation of anthrone under carefully defined conditions to prepare the cognition enhancer drug candidate 1. This process proceeds in up to 37% overall yield and is adaptable for large scale synthesis.",10.1021/jo9804339,2000-10-21,0.5906980574793472
Green Chemistry,Efficient atom and step economic (EASE) synthesis of the “smart drug” Modafinil,"We developed a post-sulfoxidation protocol for the synthesis of Modafinil that exhibits improved sustainability credentials, utilizing the recyclable heterogeneous catalyst Nafion-H.",10.1039/c6gc02623k,2016-11-30,0.5906913055938282
Tetrahedron,"The total synthesis of 10-(R,S)-C30 botryococcene and botryococcane and a new synthesis of a general intermediate to the botryococcene family",,10.1016/s0040-4039(01)80530-x,1989-01-01,0.5906899954176159
Angewandte Chemie International Edition,"Generation and Rearrangement of <i>N</i>,<i>O</i>‐Dialkenylhydroxylamines for the Synthesis of 2‐Aminotetrahydrofurans","A new diastereoselective route to 2-aminotetrahydrofurans has been developed from N,O-dialkenylhydroxylamines. These intermediates undergo a spontaneous C-C bond-forming [3,3]-sigmatropic rearrangement followed by a C-O bond-forming cyclization. A copper-catalyzed N-alkenylation of an N-Boc-hydroxylamine with alkenyl iodides, and a base-promoted addition of the resulting N-hydroxyenamines to an electron-deficient allene, provide modular access to these novel rearrangement precursors. The scope of this de novo synthesis of simple nucleoside analogues has been explored to reveal trends in diastereoselectivity and reactivity. In addition, a base-promoted ring-opening and Mannich reaction has been discovered to covert 2-aminotetrahydrofurans to cyclopentyl β-aminoacid derivatives or cyclopentenones.",10.1002/anie.201800908,2018-03-31,0.5906886195852838
Tetrahedron,"Efficient syntheses of a novel 5-thia-1-azacycl[3.3.2]azine ring system and 3H-1,4-diazacycl[3.3.2]azine derivatives",,10.1016/s0040-4039(00)00426-3,2000-04-01,0.5906871894051677
Synthesis,"An Enantioselective Synthesis of (5S,6R,11S,14R)-Acremodiol","An expeditious synthesis of the (5S,6R,11S,14R)-isomer of acremodiol was developed via a convergent route. One of the required building blocks was synthesized earlier via two sequential lipase-catalyzed secondary carbinol acetylations. The other unit was derived from (R)-2,3-cyclohexylideneglyceraldehyde as a chiral template. The bismacrolide skeleton was constructed by an intermolecular esterification reaction under Mitsunobu conditions followed by a ring-closing metathesis­ of the resultant α,ω-dialkenoic ester.",10.1055/s-0036-1588557,2017-08-29,0.5906855159243891
Journal of Organic Chemistry,Toward a Unified Total Synthesis of the Xiamycin and Oridamycin Families of Indolosesquiterpenes,"A unified synthetic strategy toward the oridamycin and xiamycin families of natural products was designed, aiming to access several natural products from a common synthetic intermediate readily prepared from geranyl acetate. Part of this strategy was successfully realized, culminating in the synthesis of oridamycin A and oridamycin B. Key steps include a Mn(III)-mediated oxidative radical cyclization to construct the trans-decalin ring, and a 6π-electrocyclization/aromatization sequence to produce the 2,3-fused carbazole. Oridamycin B was accessed through a late-stage, C-H oxidation that converted the C16 methyl to a hydroxymethyl. A variety of strategies were explored to form a chelated radical intermediate en route to xiamycin A, including enolate SET oxidation, oxo-vanadium oxidation, and atom-transfer cyclization. Unfortunately, none of these strategies provided the desired C16-epimeric trans-decalin. Exploratory studies on photoredox-catalyzed radical cyclizations yielded interesting results, including the formation of a bicyclic lactone arising from oxidative termination of the photoredox-catalyzed radical cyclization, and a double 6-endo cyclization with catalyst loadings as low as 0.01 mol%.",10.1021/acs.joc.7b02623,2017-11-24,0.5906851456922281
Chemical Science,Total synthesis of atropodiastereomers of heterodimeric <i>Amaryllidaceae</i> alkaloids: narcipavline and narcikachnine,"substituents, imposes constraints on free rotation around the C-C axis, resulting in atropisomerism, an exceedingly rare phenomenon in nature. Key steps in the synthesis encompass the utilization of a one-pot double reductive amination approach for the establishment of C-N-C bonds to merge both the galantamine (6a) and galanthindole (7) cores. Additionally, the Mitsunobu reaction and intramolecular Heck cyclization have emerged as pivotal techniques for crafting the tricyclic hydrodibenzofuran core [(-)-13], incorporating an all-carbon quaternary stereogenic center.",10.1039/d4sc04361h,2024-01-01,0.59067946600724
European Journal of Organic Chemistry,Modular Synthesis of 5‐Substituted Furan‐2‐yl <i>C</i>‐2′‐Deoxyribonucleosides and Biaryl Covalent Base‐Pair Analogues,"Abstract A modular and efficient synthesis of 5‐(hetero)arylfuran C ‐2′‐deoxyribonucleosides was developed. Friedel–Crafts C‐glycosidation of 2‐bromofuran with toluoyl‐protected methyl 2′‐deoxyribofuranoside in the presence of BF 3 · Et 2 O gave 5‐bromofuran C‐nucleosides, which were used as key intermediates for Stille or Suzuki coupling with (hetero)arylstannanes or boronic acids to afford a series of 5‐(hetero)arylfuran C‐nucleosides. 5‐Boronofuran C‐nucleoside was prepared by the Suzuki coupling of bromofuran with bis(pinacolatodiboron) or by Ir‐catalyzed C–H borylation of furan and was used for cross‐coupling with 5‐bromoheteroaryl C‐nucleosides to furnish novel covalent analogues of nucleoside pairs. The title 5‐arylfuran C‐nucleosides possess interesting fluorescence properties that may be applicable for fluorescent labeling of biomolecules.",10.1002/ejoc.201000726,2010-08-16,0.5906765486059925
Organic Letters,Practical Synthesis of Sultams via Sulfonamide Dianion Alkylation:  Application to the Synthesis of Chiral Sultams,"[reaction: see text]. A practical synthesis of sultams was developed via intramolecular sulfonamide dianion alkylation. This method has been applied toward the synthesis of chiral sultams, which are synthetically valuable as chiral auxiliaries.",10.1021/ol0356183,2003-10-01,0.5906762547884052
Tetrahedron,New Strategy for the Synthesis of the Taxane Diterpenes: Formation of the A-Ring and Introduction of the C-1 Hydroxyl Group,,10.1016/00404-0399(50)1084u-,1995-07-24,0.5906731634657205
Tetrahedron,New strategy for the synthesis of the taxane diterpenes: Formation of the A-ring and introduction of the C-1 hydroxyl group,,10.1016/0040-4039(95)01084-u,1995-07-01,0.5906731634657205
Angewandte Chemie International Edition,Synthesis of Carbazole Alkaloids by Ring‐Closing Metathesis and Ring Rearrangement–Aromatization,"Aprocess for the assembly of carbazole alkaloids has been developed on the basis of ring-closing metathesis (RCM) and ringrearrangement-aromatization (RRA) as the key steps. This method is based on allyl Grignard addition to isatin derivatives to provide smooth access to 2,2-diallyl 3-oxindole derivatives through a 1,2-allyl shift. The diallyl derivatives were used as RCM precursors to afford a novel class of spirocyclopentene-3-oxindole derivatives, which underwent a novel RRA reaction to afford carbazole derivatives. The synthetic sequence to carbazoles was shortened by combining the RCM and RRA steps in an orthogonal tandem catalytic process. The utility of this methodology was further demonstrated by the straightforward synthesis of carbazole alkaloids, including amukonal derivative, girinimbilol, heptaphylline, and bis(2-hydroxy-3-methylcarbazole).",10.1002/anie.201508746,2015-11-19,0.5906713648562762
Tetrahedron,The sequential annulation of an arene with a tetrahydrofuran provides a new route to the pseudopterosins,,10.1016/s0040-4039(99)01761-x,1999-11-01,0.5906651177219873
Tetrahedron,"A new synthesis of 4-aryl-2-benzazepine-1,5-diones",,10.1016/s0040-4039(00)77616-7,1993-04-01,0.5906611431128078
Tetrahedron,A new strategy for the preparation of 11-oxygenated steroids synthesis of (±)-adrenosterone,,10.1016/s0040-4039(98)01526-3,1998-09-01,0.5906550618964767
Journal of Organic Chemistry,"Total Synthesis of Orberryamides A, D and Their Biological Evaluation as Macrophage Differentiation Inhibitors","We report the total synthesis of orberryamides A and D and their biological evaluation as macrophage differentiation inhibitors. Both compounds were synthesized from readily available natural amino acids through a series of reactions, including condensation coupling, hydrolysis, acidification, and hydrogenation. A macrocyclic intermediate was formed by selecting a long linear chain with minimal head–tail steric hindrance, followed by mild esterification and acidification to yield orberryamide A, which was achieved in 21 steps, while orberryamide D was done in 8 steps. Biological assays indicated that orberryamides A and D may regulate the M2 phenotype of macrophages by inhibiting the expression of arginase-1 in vitro.",10.1021/acs.joc.4c02879,2025-03-07,0.5906512503417013
Synthesis,Concise Synthesis of 3-(Aminomethyl)pyrrolizidines via an In(OTf)3-Mediated Ring Rearrangement of 2-[2-(1-Pyrrolin-2-yl)-alkyl]aziridines,"In this study, an efficient ring rearrangement of 2-[2-(1-pyrrolin-2-yl)alkyl]aziridines, prepared from 2-(bromomethyl)aziridines, toward novel trans - and cis -3-aminomethyl-substituted pyrrolizidines was developed. To that end, addition of In(OTf) 3 as an appropriate Lewis acid catalyst resulted in the formation of intermediate pyrrolizidinium salts via regioselective aziridine ring opening, which were then trapped by a hydride or cyanide nucleophile. Column chromatographic purification allowed the isolation of the major trans -isomers, exclusively.",10.1055/s-0036-1588404,2017-01-31,0.590648998740291
European Journal of Organic Chemistry,Synthesis of Thiazolidine‐2‐thiones through a One‐Pot A<sup>3</sup>‐Coupling–Carbon Disulfide Incorporation Process,"A copper‐catalyzed two‐step one‐pot procedure for the synthesis of thiazolidine‐2‐thiones has been developed. The process involves a three‐component coupling of an alkyne, an aldehyde, and an amine (A 3 ‐coupling) followed by trapping the resulting propargylamine with carbon disulfide and subsequent cyclization.",10.1002/ejoc.201601103,2016-12-07,0.5906391534321193
Journal of Organic Chemistry,Syntheses of Linear Biosynthetic C<sub>25</sub>-Precursors of Leucosceptroids,An efficient synthetic approach was developed and applied to the syntheses of four linear biosynthetic C 25 -precursors of leucosceptroids. The synthesis features a Julia–Kocienski olefination and a late-stage bioinspired photo-oxidation as key steps. The immunosuppressive effects of all synthetic compounds on mouse T cells and macrophage RAW264.7 were determined.,10.1021/acs.joc.3c02796,2024-02-14,0.5906376214525552
Angewandte Chemie International Edition,Stereocontrolled Total Synthesis of (−)‐Stemaphylline,"Abstract Homologation of readily available α‐boryl pyrrolidines with metal carbenoids is especially challenging even when good leaving groups (Cl − ) are employed. By performing a solvent switch from Et 2 O to CHCl 3 , efficient 1,2‐metalate rearrangement of the intermediate boronate occurs with both halide and ester leaving groups. The methodology was used in the total synthesis of the Stemona alkaloid (−)‐stemaphylline in just 11 steps (longest linear sequence), with high stereocontrol (&gt;20:1 d.r.) and 11 % overall yield. The synthesis also features a late‐stage lithiation–borylation reaction with a tertiary amine containing carbenoid.",10.1002/anie.201611273,2017-01-18,0.59063705728088
Organic Letters,Synthesis of the C1−C9 Fragment of Callipeltoside-A,"[reaction: see text] The C1-C9 fragment of callipeltoside (17) was prepared in 12 steps and 7.2% overall yield from bicyclic lactone (+)-4. Key steps include a stereoselective epoxidation and further regiocontrolled nucleophilic opening of the oxirane ring to install two vicinal stereocenters (C5 and C6), and the use of bis(trimethylsilyl) peroxide and a catalytic amount of Sn(IV) chloride for the chemoselective Baeyer-Villiger oxidation of unsaturated cyclopentanone 15.",10.1021/ol006003y,2000-06-01,0.5906323511411322
Angewandte Chemie International Edition,Collective Synthesis of Highly Oxygenated (Furano)germacranolides Derived from <i>Elephantopus mollis</i> and <i>Elephantopus tomentosus</i>,"Abstract Germacranolides, secondary metabolites produced by plants, have garnered academic and industrial interest due to their diverse and complex topology as well as a wide array of pharmacological activities. Molephantin, a highly oxygenated germacranolide isolated from medicinal plants, Elephantopus mollis and Elephantopus tomentosus , has exhibited antitumor, inflammatory, and leishmanicidal activities. Its chemical structure is based on a highly strained ten‐membered macrocyclic backbone with an ( E , Z )‐dienone moiety, which is fused with an α‐methylene‐γ‐butyrolactone and adorned with four successive stereogenic centers. Herein, we report the first synthesis of molephantin in 12 steps starting from readily available building blocks. The synthesis features the highly diastereoselective intermolecular Barbier allylation of the β,γ‐unsaturated aldehyde with optically active 3‐bromomethyl‐5 H ‐furan‐2‐one intermediate and ensuing Nozaki–Hiyama–Kishi (NHK) macrocyclization for the construction of the highly oxygenated ten‐membered macrocyclic framework. This synthetic route enabled access to another germacranolide congener, tomenphantopin F. Furthermore, cycloisomerization of molephantin into 2‐deethoxy‐2β‐hydroxyphantomolin could be facilitated by irradiation with ultraviolet A light (λ max =370 nm), which opened a versatile and concise access to the related furanogermacranolides such as EM‐2, phantomolin, 2‐ O ‐demethyltomenphantopin C, and tomenphantopin C.",10.1002/anie.202402050,2024-03-16,0.5906299694751128
Organic Letters,"Stereoselective Synthesis of 2,6-Disubstituted 3-Piperidinols:  Application to the Expedient Synthesis of (+)-Julifloridine","[reaction: see text] The asymmetric synthesis of 2,6-disubstituted 3-piperidinols having a 2,3-cis and 2,6-trans relative stereochemistry was accomplished in three steps using the following sequence: stereocontrolled nucleophilic addition of an organomagnesium reagent to a chiral pyridinium salt; monohydrogenation of the resulting 2-substituted 1,2-dihydropyridine; and a one-pot, highly diastereoselective epoxidation-nucleophilic addition with a heteroatom nucleophile or an organometallic reagent. This methodology was applied to the expedient asymmetric synthesis of (+)-julifloridine in four steps.",10.1021/ol051022z,2005-05-28,0.5906294411968351
Synthesis,"A New Facile Synthesis of 2-Substituted 4,6-Diphenyl-1,3,5-triazines","All articles of this category A new efficient synthesis of symmetrically and unsymmetrically 2-substituted 4,6-diphenyl-1,3,5-triazines 2 by palladium-catalyzed cross coupling reaction of 2-substituted 4,6-dichloro-1,3,5-triazines 1 with phenylboronic acid is described.",10.1055/s-1993-25782,1993-01-01,0.5906273853060817
Journal of Organic Chemistry,Divergent Synthesis of Solanidine and 22-<i>epi</i>-Solanidine,"A divergent synthesis of solanidine and 22-epi-solanidine, two 25S natural steroidal alkaloids, from 25R-configured diosgenin acetate, is described. Initially, solanidine was synthesized through a series of transformations including a cascade ring-switching process of furostan-26-acid, an epimerization of C25 controlled by the conformation of six-membered lactone ring, an intramolecular Schmidt reaction, and an imine reduction/intramolecular aminolysis process. To address the epimerization issue during Schmidt reaction, an improved synthesis was developed, which also led to a synthesis of 22-epi-solanidine. In this synthesis, selective transformation of azido lactone to azido diol and amino diol was realized through a reduction relay tactic. The azido diol was transformed to solanidine via an intramolecular Schmidt reaction/N-alkylation/reduction process and to 22-epi-solanidine via an intramolecular double N-alkylation process.",10.1021/acs.joc.7b01133,2017-06-16,0.5906268213431634
European Journal of Organic Chemistry,Improved Synthesis of MediPhos Ligands and Their Use in the Pd‐Catalyzed Enantioselective N‐Allylation of Glycine Esters,"Abstract A new class of chiral C 2 ‐symmetric diphosphines (MediPhos) was recently shown to give superior results in the Pd‐catalyzed asymmetric N‐allylation of amino acid esters. We here describe a new, improved protocol for the preparation of such ligands through bidirectional S N 2‐coupling of a tartrate‐derived ditosylate with 6‐alkyl‐2‐bromophenols followed by double lithiation/phosphanylation. This method gave access to a series of nine ligands with branched alkyl substituents, which were benchmarked in the enantioselective Pd‐catalyzed N ‐allylation of tert ‐butyl glycinate with racemic ( E )‐2,8‐dimethylnona‐5‐en‐4‐yl methyl carbonate (up to 95 % ee ). In addition, the analogous transformation of tert ‐butyl glycinate with methyl ( E )‐nona‐5‐en‐4‐yl carbonate was optimized. The obtained allylic amines were then used in the stereoselective synthesis of the conformationally restricted proline‐derived dipeptide analogs ProM‐17 and ProM‐21 .",10.1002/ejoc.202100748,2021-07-22,0.5906238355979705
Organic Letters,Enantioselective Synthesis of the ABC Ring Motif of Norzoanthamine Based on Asymmetric Robinson Annulation Reactions,"An enantioselective strategy for the synthesis of tetracyclic motif 5, representing the northern fragment of norzoanthamine, is presented. Key to the strategy is the use of two asymmetric Robinson annulation reactions that produce the tricyclic ABC ring system with excellent stereoselectivity. Further functionalization at the periphery of the C ring produces compound 5 containing six contiguous stereocenters of the natural product.",10.1021/ol200966z,2011-05-26,0.5906190324397019
Journal of Organic Chemistry,"Design, Synthesis, and Biological Activities of Some Branched Carbasugars: Construction of a Substituted 6-Oxabicyclo[3.2.1]nonane Skeleton","Transformation of cyclohexa-2,4-diene-1,2-diylbis(methylene) diacetate to various carbasugars is described. Photooxygenation of a cyclohexadiene derivative gave a bicyclicendoperoxide, which was reduced with thiourea to [2-[(acetyloxy)methyl]cyclohexa-2,4-dien-1-yl]methyl acetate. Epoxidation of the remaining double bond followed by epoxide ring-opening and hydrolysis of the acetate groups gave one of the target hexols. The bicyclic endoperoxide was rearranged to a diepoxide with CoTPP. The diepoxide was reacted with sulfamic acid in acetic anhydride, resulting in the formation of a new branched carbasugar as well as in the formation of cyclitols with a 6-oxabicyclo[3.2.1]nonane skeleton. The mechanism of the formation of the products is discussed. The inhibition activity of six cyclitol derivatives was tested against α-glycosidase.",10.1021/jo300655p,2012-05-20,0.5906164649299046
Organic Letters,Total Synthesis of the Conjugation-Ready Tetrasaccharide Repeating Unit of <i>Shewanella japonica</i> Type Strain KMM 3299<sup>T</sup>,"Here we report the first total synthesis of the conjugation-ready tetrasaccharide repeating unit of Shewanella japonica type strain KMM 3299 T . The presence of rare deoxyamino sugars and installation of three consecutive 1,2- cis glycosidic linkages makes the synthesis formidable. The challenging late-stage oxidation was overcome by using a galacturonate donor. The total synthesis was completed via a longest linear sequence of 22 steps in an overall yield of 3.5% starting from d -mannose.",10.1021/acs.orglett.4c01354,2024-05-09,0.5906162972005576
Organic Letters,Directed Orthometalation and the Asymmetric Total Synthesis of <i>N</i>-Deoxymilitarinone A and Torrubiellone B,A diverted total synthesis (DTS) approach to the total synthesis of pyridone alkaloids N-deoxymilitarinone A (8) and torrubiellone B (10) has been developed. The common intermediate 14 was first assembled by a dual directed orthometalation process using a methoxymethyl group as directed metalation group. Other crucial steps include the assembly of polyenes under aldol condensation for DTS using general and concise strategy and diastereoselective synthesis of the syn-dimethyl array by an Evans aldol reaction.,10.1021/ol402820d,2013-12-02,0.5906120162617413
Synlett,Stereoselective Routes to Densely Functionalized <i>cis</i>-Hydrindanes: Synthetic Intermediates for Reserpine,"All articles of this category A new approach to functionally embellished cis -hydrindane derivative 20 , embodying the complete stereochemical pattern of ring-E of reserpine, from a readily available tricyclo[5.2.1.0 2,6 ]decan-10-one precursor via Haller-Bauer cleavage is described. Haller-Bauer cleavage - Reserpine - E-ring intermediate - cis -hydrindane synthesis",10.1055/s-1997-3218,1997-05-01,0.5906063191248688
Tetrahedron,Synthesis of isomeric coumarin-fluorene hybrids by photocyclization and the photophysical features,,10.1016/j.tetlet.2018.02.033,2018-02-15,0.5905959510403933
Tetrahedron,Synthesis of new chiral diphosphine ligand (BisbenzodioxanPhos) and its application in asymmetric catalytic hydrogenation,,10.1016/s0040-4039(02)00383-0,2002-04-01,0.5905929725189786
Tetrahedron,Synthesis of new cytotoxic E-ring modified camptothecins,,10.1016/j.tetlet.2010.09.130,2010-10-09,0.5905854248143155
Tetrahedron,A facile route to E-4-bromo-3-methyl-2-buten-1-ol: Application to the stereoselective synthesis of trisubstituted olefins,,10.1016/s0040-4039(00)93697-9,1976-01-01,0.5905794437377253
Synlett,New Aziridine Sulfide Ligands for Palladium-Catalyzed Asymmetric Allylic Alkylation,"Aziridine sulfides, a new type of chiral S,N-ligand, have been easily synthesized in a straightforward synthetic route, from an inexpensive and easily available chiral pool. They were used in the Pd-catalyzed asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl acetate with dimethymalonate anion, furnishing the alkylated product in excellent yields and stereoselectivity up to 99%.",10.1055/s-2004-825588,2004-01-01,0.5905739519729712
Journal of the American Chemical Society,Synthesis of (−)-Haliclonadiamine,Diastereoselective and enantioselective hydrogenation of the racemic β-keto ester 5 to give the enantiomerically pure (96% ee) ester 8 is reported. The conversion of the derived vinylstannane 11 to the antibiotic marine alkaloid (−)-haliclonadiamine ( 1 ) is described.,10.1021/ja962162u,1997-01-01,0.5905601140068952
Organic Letters,A Biomimetic Total Synthesis of (+)-Ainsliadimer A,"A protecting group free and biomimetic total synthesis of (+)-ainsliadimer A has been accomplished in 14 steps from α-santonin. The synthesis relies on a hydrogen bonding promoted [4 + 2]-hetero-Diels-Alder dimerization to afford the key homodimer intermediate, which demonstrates the feasibility of using nonenzymatic conditions to achieve the proposed biosynthesis.",10.1021/ol101705j,2010-09-02,0.590556643544795
Tetrahedron,A concise and efficient synthesis of salvinal from isoeugenol via a phenoxenium ion intermediate,,,2006-10-01,0.5905528124518975
Tetrahedron,A concise and efficient synthesis of salvinal from isoeugenol via a phenoxenium ion intermediate,,10.1016/j.tetlet.2006.10.131,2006-11-16,0.5905528124518975
European Journal of Organic Chemistry,"Synthesis of Four Stereoisomers of (<i>S</i>)‐2‐Methylpent‐3‐yl 3,13‐Dimethylpentadecanoate, a Sex Pheromone of the Bagworm Moth <i>Clania variegate</i>, Using Stereospecific Inversion of Secondary Sulfonates as a Key Step","Abstract Females of some lepidopteran species produce novel sex pheromones with a methyl‐branched structure, such as 2‐methylpent‐3‐yl 3,13‐dimethylpentadecanoate secreted by the bagworm moth Clania variegate . Recently, we have established a simple preparative method for the synthesis of methyl‐branched building blocks by utilizing an S N 2 reaction of chiral secondary tosylates derived from ( S )‐ and ( R )‐propylene oxides. The usefulness of these building blocks was demonstrated by their application in the synthesis of all four stereoisomers of an acid moiety in the bagworm pheromone. The enantiomeric purities of all building blocks were confirmed by enantioselective HPLC analysis. We found that a secondary mesylate was superior to the corresponding tosylate because it avoided an elimination side reaction, and racemization in the S N 2 reaction was not observed even at high temperature (150 °C). Finally, each optically active acid was esterified with ( S )‐2‐methyl‐3‐pentanol, which was synthesized by a new route starting from ( S )‐valine.",10.1002/ejoc.201300874,2013-09-04,0.590548892724613
Tetrahedron,A dehydroalanine route to an activated phenolic sparsomycin analog,,10.1016/s0040-4039(01)81255-7,1984-01-01,0.5905444487293935
Synlett,"1,2,3,4-Tetraethynylbenzene as a Template for Cobalt-Catalyzed Alkyne Cocyclizations: Synthesis of 2,3,8,9-Tetrakis(trimethylsilyl) Angular [3]Phenylene and Bent [5]Phenylene (Benzo[1′′,2′′:3,4;3′′,4′′:3′,4′]dicyclobuta[1,2-<i>b</i>:1′,2′-<i>b</i>′]bisbiphenylene)","An approach to the synthesis of bent phenylenes is described, which features 1,2,3,4-tetraethynylbenzene as starting material. Application of this synthon in CpCo-catalyzed alkyne cocyclizations allows the total synthesis of bent [5]phenylene, the seventh isomer of the family of twelve [5]phenylenes to be isolated.",10.1055/s-2006-947329,2006-10-25,0.5905368311145877
Organic Letters,Total Synthesis of (±)-Spiroaxillarone A via a Reversible Sulfa-Michael Addition,"A bioinspired strategy is described for the total synthesis of spiroaxillarone A, which exhibited significant antimalarial activity against resistant Plasmodium falciparum (IC 50 = 2.32 μM). The key steps include an intermolecular ethanethiol Michael addition, o -quinone Michael addition, and subsequent β-ethanethiol elimination. This synthetic sequence provides a potential biosynthetic pathway of spiroaxillarone A.",10.1021/acs.orglett.1c04282,2022-01-31,0.5905361270080497
European Journal of Organic Chemistry,"Synthesis of Indeno[1,2‐<i>b</i>]indole Derivatives through One‐Pot Sequential or Two‐Step Iodine‐Catalyzed C–O Activation and Palladium‐Catalyzed C–H Functionalization","Abstract An efficient route for the synthesis of indeno[1,2‐ b ]indoles as tetracyclic derivatives of indole bearing 2‐oxo‐1‐pyrrolidine moieties through one‐pot sequential or two‐step iodine‐catalyzed C–O activation and palladium‐catalyzed C–H functionalization is reported.",10.1002/ejoc.201200876,2012-08-29,0.5905314866649675
Journal of Organic Chemistry,"Formation of the 7-Oxa-1,4,10-triazatricyclo[8.2.2<sup>5,12</sup>]tetradecane-2,14-dione Ring System:  Misrouted Synthesis of a Peptidomimetic","An attempted synthesis of the tricyclic peptidomimetic 1, designed to imitate a beta-turn tripeptide in tendamistat, afforded instead the 6,6,8-ring system of 2. The key step in the synthesis entailed acylation of the hindered alpha,alpha'-disubstituted morpholine 4.2, which was approached by acylative ring opening of the 3,6-oxazabicyclo[4.2.0]octane 4.3. However, transannular rather than exocyclic cleavage occurred, giving the 1,6-oxazacyclooctane isomer 4.5. Subsequent ring closures to form the bi- and tricyclic intermediates 7.3 and 8.5 were difficult because of the strain being built into the ring systems. After completion of the synthesis, the structures of the intermediates and final product were elucidated by NMR, with three-bond, heteronuclear multiple-bond correlation experiments providing unambiguous evidence for the ring connectivity, and by molecular modeling, which allowed assignment of the stereochemistry. Compound 2 is a modest inhibitor of the target enzyme alpha-amylase (K(i) = 170 &mgr;M in 5% DMSO/water), binding with similar affinity to the tripeptide Ac-Trp-Arg-Tyr-OMe. Although the side-chain attachment points in the ring system of 2 correspond closely to the relative Calpha-positions in tendamistat (rmsd = 0.24 Å), the alignment of the Calpha-Cbeta bonds is poor, illustrating the importance of side-chain orientation in a peptidomimetic.",10.1021/jo961114p,1996-01-01,0.5905211721670895
Synlett,"One-Pot Synthesis of 1,4-Disubstituted 1,2,3-Triazoles from Aldehydes and Amines","A one-pot, three-step synthesis of 1,4-disubstituted 1,2,3-triazoles from aldehyde and amine has been developed by in situ transformation of aldehyde into alkyne, followed by diazo-transfer of amine into azide and subsequent cycloaddition. This procedure allowed the synthesis of fluorescent amino acid derivatives as well as glycoconjugate mimetics.",10.1055/s-0029-1218267,2009-10-08,0.5905211461748061
Organic Letters,Total Synthesis and Structural Revision of (+)-Yaoshanenolide B,"(+)-Yaoshanenolide B was synthesized employing as a key step an endo- and face-selective Diels-Alder reaction between natural R-(-)-α-phellandrene and the exocyclic double bond of a 5-methylene-2(5H)-furanone. The dienophile furanone was prepared by photooxygenation of a suitably substituted 2-thiophenylfuran followed by dehydration of the resulting γ-hydroxybutenolide. Through this synthesis, the initially proposed structure for (+)-yaoshanenolide B has been revised to the 1R,2S,4R,7R,1″S diastereomer.",10.1021/acs.orglett.6b02446,2016-09-13,0.5905209155676857
Organic Process Research & Development,"Continuous Flow-Facilitated CB2 Agonist Synthesis, Part 2: Cyclization, Chlorination, and Amination","A new route to the cannabinoid receptor type 2 agonist, RG7774, has been developed circumventing an alkylation with poor regioselectivity as the final step. In the new synthetic route, this side chain is incorporated from the beginning. In this article, the development of the final four transformations is detailed, using a combination of batch and flow processing. Due to poor solubility, an N -pivaloylation was performed in batch, followed by cyclization at up to 200 °C, enabled by flow processing. The following chlorination and S N Ar steps were examined in both batch and flow for improved handling of hazardous reagents and intermediates, as well as enhanced heat transfer. A workup between these two steps was found to be vital in preventing side product formation from residual dimethylamine. To achieve this on a laboratory scale, a continuous solid phase treatment was developed, whereby two cation exchange columns (containing SCX-2 silica) were cycled, with monitoring by UV/vis analysis. These four steps were demonstrated with a combined yield of 72%, which serves as a significant positive contribution to the new route’s high overall yield of 53%.",10.1021/acs.oprd.3c00036,2023-03-29,0.5905202510702727
Synthesis,[2+2] Photocycloadditions with Chiral Uracil Derivatives: Access to All Four Stereoisomers of 2-Aminocyclobutanecarboxylic Acid,"Starting from a single, chiral, bicyclic derivative of uracil, all four stereoisomers of 2-aminocyclobutanecarboxylic acid have been prepared in enantiomerically pure form, using a synthetic sequence which begins with a key photochemical [2+2] cycloaddition reaction and includes a practical cis to trans β-amino acid isomerisation procedure.",10.1055/s-2007-983759,2007-07-03,0.5905179476117329
Organic Letters,Synthesis of <i>P</i>-Stereogenic Phospholene Boranes via Asymmetric Deprotonation and Ring-Closing Metathesis,"The first examples of the asymmetric synthesis of P-stereogenic vinylic phospholene boranes are described. The synthetic approach is concise and flexible. The route involves (i) asymmetric deprotonation-allylation of a dimethyl phosphine borane; (ii) telescoped regioselective deprotonation, paraformaldehyde trapping, and hydroxyl group elimination to give a diene; and (iii) ring-closing metathesis.",10.1021/ol303253h,2012-12-21,0.5905156787384328
Tetrahedron,Progress toward the total synthesis of maytansinoids. An efficient route to two major precursors (western-southern zone),,10.1016/s0040-4039(01)94549-6,1978-01-01,0.590511612786256
Organic Letters,Synthesis of SL0101 Carbasugar Analogues: Carbasugars via Pd-Catalyzed Cyclitolization and Post-Cyclitolization Transformations,"A general approach to the stereoselective synthesis of 5a-carbasugars has been developed. The route mimics our palladium-catalyzed glycosylation/postglycosylation approach to carbohydrates in that it also utilizes a highly regio- and stereospecific palladium-catalyzed allylation and postglycosylation reaction sequence for the installation of either D- or L-cyclitols. This cyclitolization/postcyclitolization sequence was used for the enantioselective synthesis of a cyclitol analogue of SL0101, its D-sugar enantiomer, as well as several acetylation pattern analogues.",10.1021/ol101009q,2010-06-02,0.5905095455234259
European Journal of Organic Chemistry,Enantioselective Synthesis of (−)-Anaferine Dihydrochloride by a Ruthenium-Catalysed Tandem Ring Rearrangement Metathesis,"A stereoselective synthesis of (−)-anaferine dihydrochloride has been developed. The bis(tetrahydropyridine) system 10 was formed by a tandem ring rearrangement metathesis of the chiral bis(but-3-enylamino)cycloheptene derivative 9. (−)-Anaferine dihydrochloride was obtained in 23% overall yield in eleven steps and its absolute configuration was confirmed as (R,R) by this total synthesis.",10.1002/1099-0690(200208)2002:16<2855::aid-ejoc2855>3.0.co;2-1,2002-08-01,0.5905055842687403
Tetrahedron,"α-Amino 1,3-dithioketal mediated asymmetric synthesis of piperidines (L-733,060) and tetrahydrofuran glycines",,10.1016/j.tetlet.2007.11.170,2007-12-05,0.5905025761224393
Angewandte Chemie International Edition,Total Syntheses of (±)‐Aspidophylline A,Yes they can! The groups of Zhu and Ma recently reinvestigated the synthetic route to aspidophilline A. These approaches are discussed in the context of the first total synthesis of the title alkaloid that was reported by Garg and co-workers in 2011.,10.1002/anie.201400720,2014-03-05,0.59048982097444
Tetrahedron,One pot synthesis of new benzopyranopyridines via Friedlander condensation,,10.1016/j.tetlet.2012.07.013,2012-07-11,0.5904897073729133
Tetrahedron,Synthesis of 5-amino-4-cyanopyrazoles via ring opening-ring closure of 5-azido-4-iminomethylpyrazoles isolation of the intermediate,,10.1016/0040-4039(91)80835-t,1991-07-01,0.5904880082871562
Journal of Organic Chemistry,Dynamic Kinetic Asymmetric Ring-Opening/Reductive Amination Sequence of Racemic Nitroepoxides with Chiral Amines: Enantioselective Synthesis of Chiral Vicinal Diamines,"We report a highly diastereoselective synthesis of vicinal diamines by the treatment of nitroepoxides with primary amines and then a reducing agent. When using a chiral primary amine, racemic nitroepoxides are transformed into chiral diamines as a single enantiomers (>95:5 er) through a dynamic kinetic asymmetric transformation (DYKAT). The overall process is a one-pot procedure combining the exposure of nitroepoxides to chiral amines to afford diastereomeric mixtures of aminoimines and subsequent stereoselective imine reduction.",10.1021/jo400501k,2013-05-03,0.590486545671704
Organic Letters,Perylene Synthesis by the Parallel Cycloaromatization of Adjacent Enediynes,"As part of an investigation into new synthetic routes to poly(peri-naphthalene), the synthesis and cycloaromatization of tetraethynylbiphenyls is described. The temperature-dependent cyclization of biphenyls containing unsubstituted alkynes provides the desired perylene in good yield.",10.1021/ol005615f,2000-03-04,0.59048234265899
Synlett,Molecular Iodine Mediated Intramolecular Cyclization: An Efficient Method for the Synthesis of Benzoxepine Derivatives,"A simple, efficient and cost effective method for a divergent synthesis of benzoxepine derivatives using a hitherto unreported, highly regioselective, tandem iodocyclization procedure is described.",10.1055/s-0029-1219825,2010-04-13,0.5904819378993185
Chemical Science,Selective C–O bond formation via a photocatalytic radical coupling strategy: access to perfluoroalkoxylated (OR <sub>F</sub> ) arenes and heteroarenes,Synthesis of perfluoroalkoxylated (hetero)arenes (Ar–OR <sub>F</sub> ) from readily available perfluoroalkyl iodides (R <sub>F</sub> –I) through photocatalytic selective O–R <sub>F</sub> bond formation.,10.1039/c7sc01684k,2017-01-01,0.5904759322550889
Synlett,"Diastereoselective synthesis of (5<i>R</i>,7<i>R</i>)- and (5<i>R</i>,7<i>S</i>)-5,7-Dimethyl-6,7-dihydro-5<i>H</i>-dibenz[c,e]azepines","All articles of this category Starting from ( R )-1-(2-methoxyphenyl)ethylamine, the title compounds were synthesized. Key steps are a diastereoselective imine alkylation and a Pd-catalyzed biaryl coupling. The benzylic stereogenic centers of the (5 R ,7 R )-azepine induce a strong bias for the atropisomeric conformer having aS axial chirality and pseudo equatorial Me groups. diastereoselective imine alkylation - chiral azepine - Stille biaryl coupling - palladium - enantioselective lithiation",10.1055/s-2000-6558,2000-01-01,0.5904704106717608
Journal of Organic Chemistry,Formation of <i>N</i>-Alkoxyindole Framework:  Intramolecular Heterocyclization of 3-Alkoxyimino-2-arylalkylnitriles Mediated by Ferric Chloride,"A variety of functionalized N-alkoxyindole-3-carbonitrile derivatives are achieved under remarkably mild conditions by applying a FeCl3-mediated intramolecular heterocyclization of 3-alkoxyimino-2-arylalkylnitriles. This novel synthesis allows the N-moiety on the side chain to be annulated to the benzene ring as the final synthetic step, which enables the functionalization of the benzenoid portion of the indole at an early stage of the synthesis.",10.1021/jo7024477,2008-02-13,0.5904698906335625
Organic Letters,Synthesis of the Spirofungin B Core by a Reductive Cyclization Strategy,"[reaction: see text] A reductive decyanation approach to the synthesis of the core of spirofungin B has been developed. Spirofungin B has only one anomeric stabilization in the spiroacetal and was isolated along with its spiroacetal epimer, spirofungin A. The cyclization precursor was constructed from readily available starting materials. The reductive cyclization reaction was both efficient and stereoselective. The reductive cyclization strategy to spiroacetals is convergent and effective.",10.1021/ol050589c,2005-04-01,0.5904650885593513
Synlett,Unnatural Chiral N-tert-Butanesulfinyl α-Amino Acid Synthesis; A General Synthetic Strategy to N-Boc-Phenylalanine Analogue Alternatives,"This work provides a general approach to unnatural chiral N - tert -butanesulfinyl α-amino acid synthesis with high yields and excellent diastereoselectivities (dr up to 98:2). The asymmetric addition of organometallic reagents to N - tert -butylsulfinyl imino acetate proceeded with excellent diastereo- and regioselectivities even on a 10 mmol scale. The sterically constrained 2′,6′-dimethyltyrosine (Dmt) derivative was also readily prepared from commercially available and inexpensive starting materials through simple steps.",10.1055/s-0032-1317298,2012-09-21,0.5904601479639291
Organic Letters,Total Synthesis of <i>cis</i>-Solamin,"[structure: see text] A convergent total synthesis of cis-solamin and its diastereomer was accomplished using VO(acac)2-catalyzed diastereoselective epoxidation followed by cyclization of bis-homoallylic alcohol as the key step. By comparison of the optical rotation of two possible diastereomers, it is suggested that the absolute configuration of natural cis-solamin is 1a.",10.1021/ol0102803,2002-03-03,0.5904552285840418
Tetrahedron,A first convergent synthesis of the polyolic fragment of the antifungal pentaene macrolide strevertene A,,10.1016/j.tetlet.2008.07.022,2008-07-07,0.5904462206689093
European Journal of Organic Chemistry,Macrolide Core Synthesis of Calysolin IX Using an Intramolecular Glycosylation Approach,"The utility of intramolecular glycosylation for the synthesis of the 27‐membered macrocyclic ring is highlighted in this first total synthesis of the most complex resin glycoside isolated to date – Calysolin IX. Oligosaccharide‐containing macrolides core was effectively constructed by TfOH/NIS‐promoted intramolecular glycosylation of thioglycosyl donor. As the glycosidic bond must be created en route to target structure, we show that this unusual yet efficient approach can effectively reduce the number of steps in the total synthesis of complex natural macrolides. This attempt is documented as an efficient tool in the synthesis of gigantic macrolide rings thus proving their practical utility in the total synthesis of sugar‐containing targets.",10.1002/ejoc.201901480,2019-10-16,0.5904416999848765
Tetrahedron,One-step synthesis of new heterocyclic azacyanines,,10.1016/s0040-4039(00)00908-4,2000-07-01,0.5904260239291333
Journal of Organic Chemistry,"Use of Aziridines for the Stereocontrolled Synthesis of (−)-LL-C10037α, (+)-MT35214, and (+)-4-epi-MT35214","Strategies for the synthesis of the title compounds have been developed using a diastereoselective aziridination reaction of 4-O-substituted cyclohexenones. Aziridination using a chiral amine permitted resolution of a 4-hydroxycyclohexane derivative, and this resulted in the synthesis of both enantiomers of the title compound. Alternatively, the chiral 4-hydroxycyclohexenone starting material was derived from quinic acid. In both cases stereoselective epoxidation and opening of the aziridine ring with hydrazoic acid afforded the 2-azidocyclohexenone, which was transformed to the 2-acetamido group present in the natural product.",10.1021/jo402535j,2014-02-05,0.5904255074738034
Organic Process Research & Development,The Lactol Route to Fesoterodine: An Amine-Promoted Friedel–Crafts Alkylation on Commercial Scale,"We report the discovery and optimization of an amine-promoted Friedel–Crafts alkylation of cinnamaldehyde with 4-hydroxymethyl phenol. This reaction has been used successfully on commercial scale (200 kg) in the context of the manufacture of fesoterodine, a muscarinic antagonist used for the treatment of overactive bladder. Reductive aminations of diisopropylamine and lactol 4 are also discussed, as well as the resolution of the racemic amine rac -2 into its enantiomerically pure form.",10.1021/op200107g,2011-06-18,0.5904151401385112
Angewandte Chemie International Edition,Total Synthesis of the Marine Diterpenoid Blumiolide C,"First bloom: The total synthesis of the cytotoxic marine natural product blumiolide C (1) features a ring-closing metathesis (RCM) for the closure of a nine-membered ring to give the trans-bicyclo[7.4.0]oxatridecene core (see scheme; PMB=para-methoxybenzyl, TBS=tert-butyldimethylsilyl). Attachment of the side chain at C4 of the bicyclic core was achieved in a highly stereoselective manner and excellent yield through an aldol reaction/elimination sequence.",10.1002/anie.200804004,2008-11-27,0.5904105253527333
European Journal of Organic Chemistry,Towards the Synthesis of Lyngbyaloside B: Stereoselective Synthesis of the C1–C16 Macrolactone Core Segment,"Abstract A highly stereoselective synthesis of the C1–C16 macrolactone core segment of the cytotoxic macrolide lyngbyaloside B has been achieved. The synthetic strategy involved aldol additions of chlorotitanium enolates of N ‐propionyl thiazolidinethiones to achieve non‐Evans as well as Evans syn ‐propionate aldol reactions as the key steps to establish four of the seven stereogenic centres present in the macrolactone core ( 2 ). The C7 hydroxy group and tertiary hydroxy group at C13 were introduced by using different strategies for the regioselective opening of epoxides generated by Katsuki–Sharpless asymmetric epoxidation. A crucial intermolecular acyl ketene trapping by the tertiary alcohol at C13, and a subsequent ring‐closing metethesis reaction served to unite the northern and southern hemisphere subunits to construct the macrolactone core ( 2 ).",10.1002/ejoc.201300083,2013-04-09,0.5904034056627468
Journal of Organic Chemistry,Synthesis of Somatostatin Mimetics Based on the 1-Deoxymannojirimycin Scaffold,"A novel synthesis of somatostatin mimetics based on the 1-deoxymannojirimycin (DMJ) scaffold has been developed. This involved development of a route suitable for the strategic grafting of pharmacophoric tryptophan and lysine side chains to the nitrogen atom of the piperidine ring and to the primary hydroxyl group of DMJ, respectively. The novel peptidomimetics were found to bind with higher affinity to sst4 receptors than to sst5 receptors.",10.1021/jo051454n,2005-09-13,0.5903983916281331
Synlett,Synthetic Studies toward the Bicyclic Peroxylactone Core of Plakortolides,"En route to the synthesis of plakortolide E and I, we prepared a β-hydroperoxy vinyl epoxide, obtained from (R)-epi­chlorhydrin in 13 steps and 30% yield, via chemoselective methylenation with Nysted reagent in the presence of Ti(Oi-Pr)2Cl2 and regioselective Mukaiyama-Isayama hydroperoxysilylation. Unexpectedly, acid-catalyzed cyclization of this peroxy epoxide occurred exclusively through a 5-exo mode to furnish a 1,2-dioxolane; this is in contrast to the behavior of hydroxy analogues.",10.1055/s-0030-1260959,2011-07-21,0.590393006708368
Tetrahedron,A convergent organoiron approach to steroid synthesis,,10.1016/s0040-4039(00)98597-6,1985-01-01,0.5903916927144675
Organic Letters,Synthesis of the Macrocyclic Core of Leiodermatolide,"The macrocyclic core (2) of the marine macrolide leiodermatolide (1) has been synthesized in 19 steps through a convergent strategy exploiting boron aldol methodology to install the requisite stereochemistry and a selective Stille coupling reaction for controlled fragment assembly, followed by a Yamaguchi macrolactonization and carbamate introduction at the C9-OH.",10.1021/ol2017388,2011-07-14,0.5903893113808968
Journal of the American Chemical Society,"A General Synthetic Entry to <i>Strychnos</i> Alkaloids of the Curan Type via a Common 3a-(2-Nitrophenyl)hexahydroindol-4-one Intermediate. Total Syntheses of (±)- and (−)-Tubifolidine, (±)-Akuammicine, (±)-19,20-Dihydroakuammicine, (±)-Norfluorocurarine, (±)-Echitamidine, and (±)-20-Epilochneridine<sup>1</sup>","A general strategy for the synthesis of pentacyclic Strychnos alkaloids with the curan skeleton has been developed. It utilizes 3a-(2-nitrophenyl)hexahydroindol-4-one ( 23 ), which was prepared from 2-allyl-2-(2-nitrophenyl)-1,3-cyclohexanedione ( 15 ), as the common, pivotal intermediate. Three different procedures have been employed for the closure of the bridged piperidine D ring from 23: (i) an intramolecular Michael-type conjugate addition; (ii) a Ni(COD) 2 -promoted biscyclization that assembles B and D rings in a single synthetic step, and (iii) an intramolecular cyclization of an enone−propargylic silane system. When necessary, depending on the procedure used, introduction of the oxidized one-carbon substituent at C-16, closure of the indole ring, and/or adjustment of the functionality of the C-20 two-carbon chain constitute the last stages of the synthetic route to the title alkaloids. The procedure involving the cyclization of a propargylic silane has been successfully extended to the enantiospecific synthesis of (−)-tubifolidine starting from the enantiopure 3a-(2-nitrophenyl)hexahydroindolone (−)- 51, which was prepared taking advantage of the prochiral character of cyclohexanedione 15 .",10.1021/ja970347a,1997-08-01,0.5903721475051841
Angewandte Chemie International Edition,Synthesis of (±)‐Tetrapetalone A‐Me Aglycon,"The first synthesis of (±)-tetrapetalone A-Me aglycon is described. Key bond-forming reactions include Nazarov cyclization, a ring-closing metathesis promoted with complete diastereoselectivity by a chiral molybdenum-based complex, tandem conjugate reduction/intramolecular aldol cyclization, and oxidative dearomatization.",10.1002/anie.201404410,2014-07-07,0.5903715715405535
Journal of Organic Chemistry,A Convergent Route to Enantiomers of the Bicyclic Monosaccharide Bradyrhizose Leads to Insight into the Bioactivity of an Immunologically Silent Lipopolysaccharide,"The synthesis of bradyrhizose, the monosaccharide component of the lipopolysaccharide O-antigen of the nitrogen-fixing bacteria Bradyrhizobium sp. BTAi1 and sp. ORS278, has been achieved in 25 steps in an overall yield of 6% using myo-inositol and ethyl propiolate as the starting materials. The route involved the late-stage resolution of a racemic intermediate to provide both enantiomers of this unusual bicyclic monosaccharide. Both the natural d-enantiomer, and the unnatural and heretofore unknown l-enantiomer, were converted to disaccharide derivatives containing different forms of the monosaccharide (d,d; l,l; d,l; l,d). Evaluation of the synthetic compounds for their ability to act as microbe-associated molecular patterns in plants, through induction of reactive oxygen species, was investigated. These experiments suggest that the immunologically silent nature of the natural glycans is due to specific structural features.",10.1021/acs.joc.8b02206,2018-12-10,0.5903683758894919
Journal of the American Chemical Society,Total Synthesis of (−)-Batrachotoxinin A: A Local-Desymmetrization Approach,"An enantioselective total synthesis of (-)-batrachotoxinin A is accomplished based on a key photoredox coupling reaction and the subsequent local-desymmetrization operation. After the expedient assembly of the highly oxidized steroid skeleton, a delicate sequence of redox manipulations was carried out to deliver a late-stage intermediate on gram scale-and ultimately (-)-batrachotoxinin A in an efficient manner.",10.1021/jacs.9b12882,2020-02-09,0.590366917727304
Organic Process Research & Development,A Concise Asymmetric Synthesis of A β-Lactam-Based Cholesterol Absorption Inhibitor,"A concise, four-step, asymmetric synthesis of a β-lactam-based\ncholesterol absorption inhibitor, Sch 57939, was developed. The\ndiscovery of a one-step enantio- and diastereoselective synthesis\nof a &lt;i&gt;trans&lt;/i&gt;-β-lactam provided easy access to the desired three\nchiral centers. A novel zinc phenoxide-promoted ether synthesis\nwas reported for the completion of the side chain.",10.1021/op000079s,2000-07-27,0.590366150211216
Angewandte Chemie International Edition,Stereoselective Total Syntheses of (−)‐Flueggine A and (+)‐Virosaine B,"Convergent approach: the total syntheses of (-)-flueggine A and (+)-virosaine B have been accomplished in a concise and convergent manner. Key steps in these approaches were relay ring-closing metathesis reactions for rapid construction of the key intermediates, and 1,3-dipolar cycloaddition reactions for the formation of the natural products.",10.1002/anie.201208261,2012-11-21,0.590363773211679
Synlett,"A Modified Synthesis of the Antiosteoporosis Drug Alfacalcidol via a Key Photochemical Transformation of 1α-5,6-trans-Vitamin D3","Alfacalcidol (1α-hydroxyvitamin D 3 ) is an important clinical drug for the treatment of osteoporosis. Its practical synthesis has been intensively pursued across academia. The difficulties of separating 5,6- cis and 5,6- trans isomers in the current process was avoided by photochemical transformation of the 5,6- trans isomer into the 5,6- cis isomer. Employing vitamin D 3 as a starting material, alfacalcidol was obtained by a five-step reaction sequence of esterification, cyclization, oxidation, solvolysis ring-opening, and subsequent photochemical reaction. The overall yield has been greatly improved from 17% to 31%.",10.1055/s-0033-1339867,2013-10-14,0.5903628131684151
Tetrahedron,"A practical route to fluoroalkyl- and fluoroarylamines by base-catalyzed [1,3]-proton shift reaction",,10.1016/s0040-4039(00)76845-6,1994-05-01,0.5903613978282245
Angewandte Chemie International Edition,Enantioselective Hydroamidation of Enals by Trapping of a Transient Acyl Species,"An enantioselective synthesis of β-chiral amides through asymmetric and redox-neutral hydroamidation of enals is reported. In this reaction, a chiral N-heterocyclic carbene (NHC) catalyst reacts with enals to generate the homoenolate intermediate. Upon highly enantioselective β-protonation through proton-shuttle catalysis, the resulting azolium intermediate reacts with imidazole to yield the key β-chiral acyl species. This transient intermediate provides access to diversified β-chiral carbonyl derivatives, such as amides, hydrazides, acids, esters, and thioesters. In particular, β-chiral amides can be prepared in excellent yield and ee (40 chiral amides, up to 95 % yield and 99 % ee). This modular strategy overcomes the challenge of disruption of the highly selective proton-shuttling process by basic amines.",10.1002/anie.201803556,2018-04-25,0.5903607691079497
Synlett,"Ambient-Pressure Asymmetric Preparation of S,S-DICHED, a C 2-Symmetrical Director for Matteson Reactions","A synthesis of S,S-DICHED (dicyclohexylethane-1,2-diol), a C 2-symmetrical chiral director for Matteson homologations, is described. It relies on the insertion of lithiated S-2-cyclohexyloxirane into cyclohexylboronic acid pinacol ester and proceeds in three linear steps from readily available starting materials. No step requires chromatography or any specialized equipment.",10.1055/s-0036-1591530,2018-01-19,0.5903598831680827
Angewandte Chemie International Edition,Synthesis of Functionalized Medium‐Sized <i>trans</i>‐Cycloalkenes by 4π Electrocyclic Ring Opening/Alkylation Sequence,"Development of a novel synthetic method for medium-sized trans-cycloalkenes (TCAs) is described. Functionalized TCAs are readily prepared from simple cycloalkanones in a few steps, namely, enol silyl ether formation, [2+2] cycloaddition, and domino 4π electrocyclic ring opening/alkylation (conjugate addition). The first example of central-to-planar chirality transfer from enantiomerically enriched cyclobutenes to TCAs is also described.",10.1002/anie.201906665,2019-07-01,0.590359445761772
Synthesis,Synthetic Studies of Carolacton: Enantioselective Total Synthesis of C1-C8 and C9-C19 Fragments of the Molecule,"This paper describes synthetic studies towards carolacton, a highly potent antibiotic against dental caries and endocarditis related bacterium Streptococcus mutans . The synthesis of the 12-membered lactone with a diversely functionalized keto acid side chain was accomplished by utilizing a blend of chiral pool and aldol strategies. Carbon chain C1–C8 was derived by utilizing Paterson aldol methodology and a Corey–Fuchs reaction. The C9–C19 chain was prepared by means of iterative Evans asymmetric alkylations and an E -selective cross-metathesis reaction.",10.1055/s-0033-1339500,2013-08-15,0.590358517155883
Tetrahedron,"Total synthesis of an anticancer agent, mucocin. 1. Stereoselective synthesis of the left-half segment",,10.1016/s0040-4039(98)02439-3,1999-01-01,0.5903495932990305
Organic Letters,Total Synthesis of Grandisine D,Total synthesis of grandisine D (5) was achieved by a Brønsted acid mediated Morita-Baylis-Hillman (MBH) ring-closure reaction and stereoselective aldol condensation with (S)-5-methylcyclohexenone (9) as key steps. The MBH approach was also applicable for the construction of the aza-fused bicyclic systems of pyrrolizidine and stemona alkaloids.,10.1021/ol900032h,2009-02-09,0.5903490573417913
Journal of Organic Chemistry,Synthesis of the Pentacylic Core of (+)-Salvileucalin B,A concise preparation of the prochiral pentacyclic core of (+)-salvileucalin B is presented. The key feature in the synthesis is the Cu-catalyzed intramolecular cyclopropanation of a symmetrical indane-derived α-diazo β-keto ester. This symmetry is carried through the remainder of the synthesis. This practical approach could allow the ready preparation of derivatives for further chemical and biological studies of this class of natural products.,10.1021/jo500164x,2014-03-24,0.5903487094321255
Journal of Organic Chemistry,A nitrone-based approach to the enantioselective total synthesis of (-)-anisomycin,This paper describes a new synthetic approach to (-)-anysomycin in which the crucial step is an organomagnesium addition to a chiral nitrone.,10.1021/jo00030a051,1992-02-01,0.5903477537170998
Organic Letters,A Concise Total Synthesis of Breitfussin A and B,"The first total synthesis of breitfussin A and B is described. The approach features two palladium-catalyzed cross-couplings installing the indole and pyrrole onto the oxazole core and selective lithiation/iodination of a common indole-oxazole fragment providing 2,4-diiodinated or 2-iodinated oxazoles as potential precursors for breitfussin A and B, respectively. An unexpected acid promoted deiodination was utilized in the synthesis of breitfussin B. Comparison of the synthetic material with previously reported spectral data of isolated breitfussin A and B verified the structure of the breitfussin framework.",10.1021/ol503348n,2014-12-16,0.5903443771526575
Synlett,"Studies on the Synthesis of Croomine: Synthesis of the Tricyclic B,C,D-Ring Core Structure<b />","A convergent and asymmetric synthesis of the tricyclic B,C,D-ring core structure of croomine has been achieved, using aminolysis reactions of chiral vinyl epoxides and the RCM reaction.",10.1055/s-2004-817773,2004-01-01,0.5903423063405338
Journal of Organic Chemistry,First Total Synthesis of J<sub>2</sub> Isoprostane,"A stereoselective Julia-Lythgoe olefination followed by an efficient 1,3-allylic transposition of the C-9 hydroxyl group of compound 13 has allowed the first total synthesis of J(2) isoprostane (1), a recently discovered member of the growing isoprostane family. This elusive compound opens up numerous new avenues for the molecular biology of cyclopentenone prostaglandins which are endowed of intriguing biological effects such as antitumor, antiinflammatory, and antiviral activities. In principle, our approach is flexible enough to allow an easy synthesis of other isoprostanes of the J family following the same methodology.",10.1021/jo034658h,2003-07-01,0.5903403433675145
Organic Process Research & Development,Large-Scale Candoxatril Asymmetric Hydrogenation,"Ruthenium-catalyzed asymmetric hydrogenation was used to prepare tons of a key chiral succinate intermediate for clinical trials quantities of candoxatril. MeOBiphep was used as the ligand, and the catalyst was generated in situ from RuCODBismethylallyl. THF was the best cosolvent for the reaction leading to a selective hydrogenation and a process which was readily amenable on large scale.",10.1021/op010005w,2001-05-12,0.5903394195152241
European Journal of Organic Chemistry,Glutarimide Alkaloids Through Multicomponent Reaction Chemistry,"A concise four step synthetic route for glutarimide alkaloids of high biological interest is presented. The scaffold is accessed via an Ugi four component reaction, hereby introducing two points of variation. This is followed by a hydrolysis, a cyclization under mild conditions, and an amine deprotection. The diastereomers of the cyclized intermediate can be easily separated, thus leading to optically pure alkaloids. By this route, four natural products and ten derivatives were synthesized. The scope and limitations of the synthetic methodology were investigated.",10.1002/ejoc.201801276,2018-09-24,0.5903378587751887
Synthesis,Stereoselective Synthesis of Northern Fragment of Eribulin Mesylate from d-Mannose,"Stereoselective synthesis of northern fragment of eribulin mesylate is reported by coupling of the C1–C13 fragment with the C28–C35 fragment. The key steps involved in this synthesis are butyllithium-facilitated coupling between sulfone and aldehyde, then Dess–Martin periodinane oxidation followed by samarium(II) iodide mediated desulfonylation.",10.1055/s-0036-1591769,2018-02-21,0.5903342842632658
Organic Letters,Enantioselective Reductive Coupling of Alkynes and α-Keto Aldehydes via Rhodium-Catalyzed Hydrogenation:  An Approach to Bryostatin Substructures,"Hydrogen-mediated reductive coupling of glyoxal 2 and 1,3-enyne 3 provides alpha-hydroxy ketone 4 in 70% yield and 91% enantiomeric excess. Notably, the benzylic ether and diene side chain of 4 remain intact under the conditions of hydrogen-mediated coupling. In four steps, alpha-hydroxy ketone 4 is converted to pyrans 8 and 9, which embody key structural features of the bryostatin recognition domain.",10.1021/ol052976s,2006-01-31,0.5903335271632415
Tetrahedron,A novel one-step synthesis of quinolinium salts and 4-quinolones from formanilides,,10.1016/s0040-4039(00)73654-9,1993-05-01,0.5903285351996577
Synlett,A Stereoselective and Convergent Synthesis of a C<sub>21</sub>-C<sub>34</sub>Fragment of FK506,"All articles of this category The synthesis of a C 21 to C 34 fragment of FK506 is described. Fragment 30a is constructed by a regio- and stereoselective Takai coupling of alkyne 4 and the aldehyde 5 which in turn was prepared from 3-deoxy-1,2:5,6-di-O-isopropylidene-α- D -ribohexofuranose ( 16 ).",10.1055/s-1993-22635,1993-01-01,0.5903246933315276
European Journal of Organic Chemistry,"Synthesis and Resolution of BICOL, a Carbazole Analogue of BINOL","The synthesis and resolution of a novel chiral C2-symmetric bicarbazolediol (BICOL), is reported. The key step in the synthesis is the copper(II)-catalysed oxidative phenol coupling of 3-hydroxycarbazole. Menthyl chloroformate is used as resolving agent for the separation of the two enantiomers of BICOL. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)",10.1002/1099-0690(200206)2002:12<1952::aid-ejoc1952>3.0.co;2-l,2002-06-01,0.5903239476845754
Angewandte Chemie International Edition,Chlorophyll Breakdown by a Biomimetic Route,"Colorless nonfluorescent chlorophyll catabolites (NCCs), the final products of endogenous chlorophyll breakdown in higher plants, were prepared by biomimetic partial synthesis from chlorophyll a. A nonstereoselective variant of the synthesis also provided an entry to the enantiomers of natural NCCs.",10.1002/anie.200705330,2008-03-07,0.5903128176343464
Angewandte Chemie International Edition,Enantioselective Total Synthesis and Absolute Configuration Assignment of (+)‐Tronocarpine Enabled by an Asymmetric Michael/Aldol Reaction,We present the first asymmetric total synthesis and absolute configuration determination of (+)-tronocarpine. The [6.5.7.6.6] pentacyclic core was constructed at an early stage by using a sequential cyclization strategy through a newly developed catalytic asymmetric Michael/aldol cascade to build the aza[3.3.1]-bridged cycle and a tandem reduction/hemiamidation procedure to assemble the seven-membered lactam. The side-chain functionalities were incorporated at a late stage by several appropriately orchestrated manipulations under mild conditions. The synthesis of enantiomerically pure (+)-tronocarpine was achieved through a 20-step longest linear sequence from tryptamine.,10.1002/anie.201914868,2019-12-12,0.5903117101906795
Synthesis,"Synthetic Studies Using α,β-Unsaturated Nitriles: A One-Step Synthesis of Hexahydropyrimidine Derivatives",,10.1055/s-1984-30998,1984-01-01,0.590311368593355
Journal of Organic Chemistry,"A Short Route toward Chiral, Polyhydroxylated Indolizidines and Quinolizidines","In this paper, a rapid route toward functionalized bicyclic alkaloids is presented. In only three steps, an easily accessible carbohydrate derivative was converted into iodomethyl indolizidine 13, which can equilibrate to the corresponding iodoquinolizidine 15. We provide strong evidence that this equilibration proceeds via an aziridinium ion intermediate. Furthermore, nucleophilic substitution of the iodomethyl indolizidine as well as the aziridinium intermediate gives access to highly functionalized indolizidine and quinolizidine alkaloids.",10.1021/jo0350662,2003-11-11,0.590305988286252
Journal of Organic Chemistry,"Total Synthesis of (±)-Maistemonine, (±)-Stemonamide, and (±)-Isomaistemonine","A full account of the total synthesis of (±)-maistemonine, (±)-stemonamide, and (±)-isomaistemonine is presented. Two approaches have been developed to construct the basic pyrrolo[1,2-a]azepine core of the Stemona alkaloids, featuring a tandem semipinacol/Schmidt rearrangement of a secondary azide and a highly stereoselectively desymmetrizing intramolecular Schmidt reaction, respectively. To build the common spiro-γ-butyrolactone, a new protocol was carried out by utilizing an intramolecular ketone-ester condensation as the key transformation. The vicinal butyrolactone moiety of (±)-maistemonine was stereoselectively introduced via a one-pot procedure involving the epimerization at C-3 and carbonyl allylation/lactonization. Moreover, (±)-stemonamide was divergently synthesized from a common intermediate, and (±)-isomaistemonine was obtained via the epimerization of (±)-maistemonine at C-12.",10.1021/jo202042x,2011-11-15,0.5903055355409986
Tetrahedron,A new diastereoselective synthesis of (±) cis 1-aminoindoloquinolizidine,,10.1016/s0040-4039(00)60682-2,1993-08-01,0.5902995512390203
Synthesis,Synthesis of (±)-γ-Lycorane by Using an Intramolecular Friedel–Crafts Reaction,"A total synthesis of γ-lycorane has been achieved by employing N-tosylpyrrole as a key building block. The synthesis employs both an intermolecular and an intramolecular Friedel–Crafts reaction, as well as a completely diastereoselective hydrogenation of a late-stage pyrrole intermediate.",10.1055/s-0036-1589067,2017-07-20,0.5902976411884265
Organic Letters,"Efficient Synthesis of the C(1)−C(9) Fragment of Amphidinolides C, C2, and F","The synthesis of the C(1)-C(9) fragment of amphidinolides C, C2, and F was achieved by using a vinyloguous Mukaiyama aldol reaction on a chiral aldehyde with a silyloxyfuran and by using a C-glycosylation of a lactol derivative with an acetyl oxazolidinethione. From the available chiral acetonide-glyceraldehyde, all the stereogenic centers were perfectly induced along the synthesis. The C(1)-C(9) fragment was synthesized as a vinyl stannane at C(9) in 10 steps, with 16% yield.",10.1021/ol1021228,2010-09-30,0.590278025971284
Tetrahedron,A novel selenium-mediated spiroannelation : one-step preparation of d1-theaspirane fron α-dihydroionol,,10.1016/s0040-4039(00)98772-0,1985-01-01,0.5902704717647969
Tetrahedron,New synthetic routes to 9(0)-methanoprostacyclin. A highly stable and biologically potent analog of prostacyclin,,10.1016/s0040-4039(01)93525-7,1979-01-01,0.5902678391094024
Organic Letters,A Short Covalent Synthesis of an All-Carbon-Ring [2]Rotaxane,"While the current supramolecular syntheses of [2]rotaxanes are generally efficient, the final product always retains the functional groups required for non-covalent preorganization. A short and high-yielding covalent-template-assisted approach is reported for the synthesis of a [2]rotaxane. A terephthalic acid template core preorganizes the covalently connected ring precursor fragments to induce a clipping-type cyclization over the thread moiety. Cleavage of the temporary ester bonds that connect the ring and thread fragments liberates the [2]rotaxane.",10.1021/acs.orglett.7b00877,2017-04-24,0.5902677571498981
Journal of the American Chemical Society,DYKAT of Baylis−Hillman Adducts:  Concise Total Synthesis of Furaquinocin E,"Baylis-Hillman adducts are easily accessible building blocks; the lack of asymmetric versions of the Baylis-Hillman reaction has however precluded their widespread use in asymmetric synthesis. A Pd-catalyzed DYKAT on carbonates derived from Baylis-Hillman adducts, followed by a reductive Heck reaction, allows the enantio- and diastereoselective construction of dihydrobenzofurans in a very efficient manner. These synthons represent the core structure of the furaquinocins. Introduction of different side chains and use of different squaric acid derivatives for the construction of the naphthoquinone allow the flexible synthesis of this class of natural products. This new approach is successfully applied to the synthesis of furaquinocin E and an analogue.",10.1021/ja0277834,2002-09-07,0.590259694080478
Organic Letters,MsOH Promoted Divergent Synthesis of 4-Arylidene Isoxazolidines and Isoxazolines from <i>O</i>-Propargyl Hydroxylamines and Aldehydes,"Temperature-dependent, Brønsted-acid-mediated divergent synthesis of 4-arylidene isoxazolidines and isoxazolines from O -propargyl hydroxylamines is developed. A series of control and crossover experiments have been carried out, revealing that the formation of 4-arylidene isoxazoline proceeds through an alkyne–oximium cyclization, ring-opening reaction, and subsequent condensation. Synthetic versatility of the developed methodology was highlighted in the synthesis of 3-aminoacrylaldehyde, β-hydroxy ketone, and isoxazole derivatives.",10.1021/acs.orglett.5c01383,2025-05-17,0.5902527703787409
Synlett,Synthetic Studies of Tedanolide. 4. Stereoselective and Efficient Synthesis of the C13-C23 Part,All articles of this category The C13-C23 part ( 5 ) of tedanolide ( 1 ) was synthesized starting from enantiomeric methyl ( R )- and ( S )-3-hydroxy-2-methylpropionates ( 8 ) via coupling between the C13-C17 aldehyde ( 6 ) and the C18-C21 iodoalkene ( 7 ). macrolide - cytotoxic activity - aldol reaction - benzyl protecting group,10.1055/s-1999-2730,1999-06-01,0.5902472393683896
Tetrahedron,Asymmetric synthesis of (−)-denticulatins A and B via group-selective aldolization of a meso dialdehyde with a chiral N-propionylsultam,,10.1016/0040-4039(95)00787-d,1995-06-01,0.590246800396008
Angewandte Chemie International Edition,Diastereoselective Total Synthesis of (±)‐Schindilactone A,"All together: A concise strategy for the first diastereoselective total synthesis of (±)-schindilactone A is reported. The synthesis features a ring-closing metathesis, a thiourea/cobalt-catalyzed Pauson–Khand reaction, and a thiourea/palladium-catalyzed carbonylative annulation reaction. The chemistry can be applied to the synthesis of structures related to schindilactone A.",10.1002/anie.201103088,2011-07-07,0.5902420134118327
Tetrahedron,Selective synthesis of Neu5Ac2en and its oxazoline derivative using BF3·Et2O,,10.1016/j.tetlet.2009.01.117,2009-01-28,0.590226582396645
Angewandte Chemie International Edition,Cover Picture: Enantioselective Total Synthesis of Amphidinolide F (Angew. Chem. Int. Ed. 32/2012),"Hidden symmetry within the THF-containing moieties of the macrocycle of amphidinolide F led S. Mahapatra and R. G. Carter to employ a synthetic strategy including a common intermediate, as reported in their Communication on page 7948 ff. The cover picture highlights key steps of the total synthesis as well as the locations on both sides of the Pacific of the initial characterization (Hokkaido University) and first synthesis (Oregon State University) of the natural product.",10.1002/anie.201205172,2012-07-18,0.5902191684895108
Organic Letters,Magnesiate Addition/Ring-Expansion Strategy To Access the 6–7–6 Tricyclic Core of Hetisine-Type C<sub>20</sub>-Diterpenoid Alkaloids,"-diterpenoid alkaloids is reported. This strategy employs a Diels-Alder cycloaddition to assemble a fused bicyclic anhydride intermediate, which is elaborated to a vinyl lactone-acetal bearing an aromatic ring in five steps. Aromatic iodination is followed by magnesium-halogen exchange with a trialkyl magnesiate species, which undergoes intramolecular cyclization. Subsequent oxidation provides the desired 6-7-6 tricyclic diketoaldehyde, with carbonyl groups at all three positions for eventual C-N bond formation and subsequent elaboration.",10.1021/acs.orglett.7b02260,2017-08-18,0.5902172742622618
European Journal of Organic Chemistry,"3‐(Arylamino)‐1,2,4‐triazin‐5‐one: A Novel Synthesis and Its Use","Abstract An optimized procedure is given for the synthesis of novel 3‐(arylamino)‐1,2,4‐triazin‐5‐one building blocks from commercially available material. By employing these building blocks, a practical protocol is described for the functionalization of the 5‐position of the triazine core with anilines orphenols.",10.1002/ejoc.201000242,2010-04-12,0.5902160705644255
Tetrahedron,13-Step total synthesis of Dendrodolide K following iterative Bartlett–Smith iodocarbonate cyclization,,10.1016/j.tetlet.2015.09.126,2015-10-02,0.590210124262412
Organic Letters,Synthetic Studies toward Phorboxazole A. Stereoselective Synthesis of the C<sub>28</sub>−C<sub>46</sub> Side Chain Fragment,A stereoselective synthesis of the C(28)-C(46) fragment (3) of phorboxazole A is described. Key advances include an enantioselective allylation to establish the stereochemistry of the tetrahydropyran unit and a useful SmI(2)-mediated modification of the Barbier reaction of iodomethyloxazole 15 with aldehyde 14.,10.1021/ol0063656,2000-08-30,0.5902071001323048
Journal of the American Chemical Society,Cyclization Cascades via<i>N</i>-Amidyl Radicals toward Highly Functionalized Heterocyclic Scaffolds,"The addition of a variety of radicals to the double bond of N-(arylsulfonyl)acrylamides can trigger cyclization/aryl migration/desulfonylation cascades via amidyl radical intermediates 2. Herein, we demonstrate the synthetic utility of these intermediates in subsequent C-C and C-X bond-forming events to rapidly build up molecular complexity. First, we describe a regioselective one-pot synthesis of CF3-, SCF3-, Ph2(O)P-, and N3-containing indolo[2,1-a]isoquinolin-6(5H)-ones from N-[(2-ethynyl)arylsulfonyl]acrylamides through a multi-step radical reaction cascade. The process involves the one-pot formation of four new bonds (one C-X, two C-C, and one C-N), a formal 1,4-aryl migration, and desulfonylation of the starting material. Second, we present a one-pot synthesis of 3,3-disubstituted-2-dihydropyridinones from N-(arylsulfonyl)acrylamides and 1,3-dicarbonyl compounds. In this case, a silver-catalyzed radical cascade process involving the sequential formation of two new C-C bonds and one C-N bond, a formal 1,4-aryl migration, and desulfonylation of the starting material explains the regioselective formation of densely functionalized heterocycles in a straightforward manner. Control experiments have unraveled the key intermediates as well as the sequence of individual steps involved in these transformations.",10.1021/ja5115858,2015-01-06,0.5902059366349421
European Journal of Organic Chemistry,Enantioselective Synthesis of <i>cis</i> and <i>trans</i> 4‐Aminopipecolic Acids as γ‐Amino Acids for the Construction of Cyclic RGD‐Containing Peptidomimetics Antagonists of α<sub>V</sub>β<sub>3</sub> Integrin,"A stereodivergent strategy to obtain enantiopure cis and trans 4‐aminopipecolic acids (4‐APAs) in a suitably protected form for peptide synthesis has been devised starting from a common, known precursor in turn easily prepared from commercial ( R )‐4‐cyano‐3‐hydroxybutyric acid ethyl ester. The two isomers were efficiently obtained in 40 % and 23 % overall yields, respectively, in seven and ten steps. To demonstrate their usefulness in peptidomimetic synthesis, both 4‐APA isomers were incorporated as γ‐amino acids in a cyclic RGD‐containing sequence, although for the trans 4‐APA isomer a further amino acid in the sequence (L‐Phe) was needed to allow ring closure. The two cyclopeptides were tested as α V β 3 integrin antagonists in comparison with cilengitide.",10.1002/ejoc.202000634,2020-06-11,0.5901985433552641
Angewandte Chemie International Edition,"Organocatalytic Asymmetric Construction of 2,6‐Diazabicyclo‐[2.2.2]octanes by Harnessing the Potential of an 3‐Oxindolium Ion Intermediate","Due to its structural complexity and intrinsic sensitivity of bridged aminal junction, 2,6-diazabicyclo[2.2.2]octane (2,6-DABCO) has remained a highly desirable target in synthetic chemistry. However, the asymmetric access to this unit is still insufficient and hampered by the need for meticulously created functionalities for intricate double aza-cyclizations. Herein, we have developed a novel enantio- and diastereoselective protocol to access polycyclic chiral 2,6-DABCOs under metal-free conditions. This domino process involves the amine-catalyzed [4+2] annulation between glutaraldehyde and 2-arylindol-3-ones, followed by an acid-mediated Pictet-Spengler reaction/intramolecular aza-cyclization cascade sequence with tryptamine by trapping of in situ generated 3-oxindolium ion intermediate for the first time. Overall, 2,6-DABCOs fused with medicinally relevant scaffolds were isolated with good yield and excellent stereoselectivity by constructing five new bonds and four stereocenters in a one-pot operation.",10.1002/anie.202416042,2024-10-15,0.590195415656909
Synthesis,Total Synthesis of (+)-Kingianin A by Enantioselective Cycloaddition of Strained Cyclobutenone,Abstract We report here the first asymmetric total synthesis of (+)-kingianin A via dimerization of an enantioenriched bicyclo[4.2.0]octadiene. The synthesis features a chiral oxazaborolidinium ion catalyzed Diels–Alder reaction of strained cyclobutenone and stereoselective functionalization of the cyclobutane ring. A preliminary biological study indicated that (+)-kingianin A exhibits potent anticancer activities.,10.1055/s-0041-1737339,2022-02-08,0.5901954079799968
Tetrahedron,"Structure of argifin, a new chitinase inhibitor produced by Gliocladium sp.",,10.1016/s0040-4039(00)00099-x,2000-03-01,0.5901927636831589
Journal of Organic Chemistry,"Synthesis of Methyl 1-Hydroxy-6-oxo-2-cyclohexenecarboxylate, a Component of Salicortin and Tremulacin, and the Monomer of Idesolide","We have developed a short and practical first synthesis of methyl 1-hydroxy-6-oxo-2-cyclohexenecarboxylate (2), which has been known as a component of salicortin and tremulacin since 1970. Birch reduction of the SEM ether of methyl salicylate followed by oxidation of the intermediate enolate with (-)-camphorsulfonyloxaziridine afforded the SEM enol ether of 2. Hydrolysis of the SEM enol ether afforded 2. We did not observe the dimerization of either racemic or optically enriched 2 to give idesolide (1).",10.1021/jo701512w,2007-09-15,0.5901910498855344
Organic Process Research & Development,An Improved Process for Trimethobenzamide Hydrochloride,"An improved process for the preparation of trimethobenzamide hydrochloride conforming to regulatory specification is reported. Specifically, a process for the preparation of trimethobenzamide hydrochloride, which is free from the associated impurities that are normally encountered during coupling of 4-(2-dimethylaminoethoxy)benzyl amine with 3,4,5-trimethoxy benzoic acid is described.",10.1021/op400113a,2013-06-28,0.5901867456060734
Organic Process Research & Development,"A Scalable Synthesis of (<i>R</i>,<i>R</i>)-2,6-Dimethyldihydro-2<i>H</i>-pyran-4(3<i>H</i>)-one","A scalable synthesis of ( R, R )-2,6-dimethyldihydro-2 H -pyran-4(3 H )-one is reported. Key to this strategy is the Ti(O i Pr) 4 -catalyzed Kulinkovich cyclopropanation of silyl protected ( R )-ethyl 3-hydroxybutanoate, and subsequent oxidative fragmentation of the cyclopropanol. The resulting vinyl ketone intermediate was then subjected to oxidative Heck cyclization to form the enone substrate required for conjugate addition. A diastereoselective copper-catalyzed Grignard addition procedure was implemented to install the requisite methyl group, with the inclusion of 1,3-bis(diphenylphosphino)propane and trimethylsilyl chloride greatly increasing the robustness of this process.",10.1021/op500135x,2014-06-12,0.5901844065765054
Journal of Organic Chemistry,Catalytic Asymmetric Total Synthesis of (+)-Lactacystin,"Total synthesis of (+)-lactacystin, a potent and selective proteasome inhibitor, was accomplished using a catalytic enantioselective Strecker reaction of a ketoimine as the initial key step. An enone-derived N-phosphinoyl ketoimine 7 was selected as a stable masked alpha-hydroxy ketoimine analogue. Excellent enantioselectivity (98% ee) and practical catalyst activity were produced under the optimized catalyst preparation method using 2.5 mol % Gd{N(SiMe3)2}3 as a metal source and 3.8 mol % D-glucose-derived ligand 8. This reaction was conducted on a 5 g scale. The chiral tetrasubstituted C-5 carbon efficiently controlled the stereochemistry of the other three chiral centers of lactacystin. Chelation-controlled Meerwein-type reduction of ketone 5 using i-PrMgBr (originally reported by Kang in a related substrate) selectively produced the desired secondary alcohol at the C-9 position. The C-6 hydroxy and C-7 methyl groups were introduced via a silyl conjugate addition followed by the Tamao oxidation and Donohoe methylation, respectively, in a highly stereoselective manner. A practical amount of enantiomerically pure clasto-lactacystin beta-lactone (2), the biologically active form of (+)-lactacystin, can be synthesized using this route. clasto-Lactacystin beta-lactone (2) was converted to (+)-lactacystin following the reported procedure.",10.1021/jo0524223,2006-01-07,0.5901793397640175
Synlett,Total Synthesis of Valerenic Acid,"Valerenic acid is a major constituent of valerian root. It exhibits modulatory activity on the GABAA receptor and thus represents a potential new lead structure for the discovery of new an­xiolytics. Here we present the enantioselective total synthesis of valerenic acid, which departs from natural (R)-pulegone and proceeds through a bicyclic ketone as the central intermediate. Key transformations are the stereoselective reduction of a 3,4-disubstituted cyclohexenone and a microwave-assisted Wittig reaction.",10.1055/s-0029-1217378,2009-06-16,0.5901791203814507
Tetrahedron,A novel approach for the synthesis of Crizotinib through the key chiral alcohol intermediate by asymmetric hydrogenation using highly active Ir-Spiro-PAP catalyst,,10.1016/j.tetlet.2014.01.053,2014-01-21,0.5901738545007431
Organic Process Research & Development,Preparation of Ethynylbenzene Derivatives from Substituted Benzaldehydes,"We have tested a number of synthetic methods for large-scale synthesis of targeted substituted aromatic alkyne ( S )-[4-(3-chloro-5-ethynyl-4-fluoro-phenyl)-1-methyl-butyl]-carbamic acid benzyl ester ( 1 ). This research resulted in an improved method for the Corey–Fuchs approach to alkyne synthesis from aldehydes. Importantly, we have shown that the use of P(OCH 3 ) 3 /CBr 4 in toluene for the synthesis of the dibromo-methylene intermediate ( S )-{4-[3-chloro-5-(2,2-dibromo-vinyl)-4-fluoro-phenyl]-1-methyl-butyl}-carbamic acid benzyl ester ( 5 ) allows the synthesis of alkyne 1 under conditions that may be amenable for scaling-up. Since this method was developed, multiple batches of alkyne 1, each approaching 100 g in size, have been prepared under process-friendly conditions, as well as multigram batches of other alkynes.",10.1021/acs.oprd.9b00063,2019-03-26,0.5901734441161153
Journal of the American Chemical Society,Asymmetric Total Synthesis of Antibiotic Elansolid A,"Elansolid A is a structurally complex polyketide macrolactone natural product that exhibits promising antibacterial properties. Its challenging asymmetric total synthesis was achieved by a convergent strategy, in which the tetrahydroindane core of the molecule and an eastern vinyl iodide moiety were combined as the main fragments. The central tetrahydroindane motif was constructed with high stereoselectivity by a bioinspired intramolecular Diels-Alder cycloaddition, generating four stereogenic centers in a single step. The stereocontrol of this key step could be achieved by virtue of a 1,3-allylic strain generated by the temporary introduction of a steric-directing iodine substituent on the substrate. The formation of the macrolactone motif that completes the synthesis was achieved via two different retrosynthetic disconnections, namely, a Suzuki-Miyaura cross-coupling or an alternative Mukaiyama esterification reaction.",10.1021/jacs.2c01133,2022-04-12,0.5901706139997265
Tetrahedron,"A new and facile synthesis of methyl 3-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxylate",,10.1016/j.tetlet.2010.11.076,2010-11-20,0.5901688490081846
Journal of Organic Chemistry,Angucycline C5 Glycosides: Regio- and Stereocontrolled Synthesis and Cytotoxicity,"This study discloses a general and convergent route for the regio- and stereospecific construction of the C5 glycosyl angucycline framework of mayamycin. C-Glycosidation, dearomatization, and Hauser annulation are the key steps. The synthetic analogues show cytotoxicity against different human cancer cell lines with IC50 values between 16.4 and 1.2 μM.",10.1021/jo4013892,2013-08-28,0.5901642159727675
Organic Letters,Total Synthesis of (−)-Callystatin A,"[reaction: see text] A convergent enantioselective synthesis of the natural product (-)-callystatin A (1) is described. Key features of the synthesis include a lipase-mediated kinetic resolution to install the C5 lactone stereochemistry, a hydrozirconation-based approach to the C8-C9 trisubstituted (Z)-olefin, and a stereoselective cross-coupling of a vinyl dibromide to install the C14-C15 trisubstituted (E)-olefin.",10.1021/ol048664r,2004-08-11,0.5901641854824893
Synlett,Synthesis of (±)-trans-Indolizidine-8-carboxylic Acid,"A facile synthesis of a novel amino acid, trans-indolizidine-8-carboxylic acid, is described. .",10.1055/s-0030-1259558,2011-02-11,0.5901627142948547
Tetrahedron,"A novel, base-labile fluorous amine protecting group: synthesis and use as a tag in the purification of synthetic peptides",,10.1016/j.tetlet.2003.09.220,2003-11-14,0.5901626823519012
Journal of the American Chemical Society,Total Synthesis of Epicoccin G,"An expedient enantioselective total synthesis of epicoccin G and related dithiodiketopiperazines through a strategy featuring direct two-directional sulfenylation, photooxygenation, and Kornblum-DeLaMare rearrangement is described.",10.1021/ja2032635,2011-05-06,0.5901549261641172
Tetrahedron,A new synthesis of 3-arylthioindoles as selective COX-2 inhibitors using PIFA,,10.1016/j.tetlet.2004.03.153,2004-04-21,0.5901543172622363
Organic Letters,Total Synthesis of the Marine Metabolite (−)-Clavosolide D,"The first total synthesis of the marine natural product (-)-clavosolide D is described confirming the structure of the unsymmetrical 16-membered diolide glycosylated by permethylated d-xylose moieties. Following efficient assembly of the two tetrahydropyrans using stereoselective Prins cyclizations, the side chains were introduced via an allylation/isomerization/anti cyclopropanation sequence; the final macrolactonization step was achieved under Yamaguchi conditions.",10.1021/ol800386d,2008-03-21,0.5901534420515806
Synlett,"Enantiotopical Synthesis of Carbazoquinocins A and D, The Potent Lipid Peroxidation Inhibitors from Streptomyces violaceus 2448-SVT2","All articles of this category Carbazoquinocins A and D, the potent lipid peroxidation inhibitors isolated from Streptomyces violaceus , have been synthesized for the first time in a chiral way. The synthesis has led us to presume the absolute configuration of natural carbazoquinocin A as S . enantiotopical synthesis - carbazoquinocins - configuration of carbazoquinocin A - lipid peroxidation inhibitor - chiral O -benzylglycidol",10.1055/s-1996-5618,1996-09-01,0.5901457040484346
Tetrahedron,"Preparation of, and alkylation of enolate anions with, dimethyl 3-bromo-2 ethoxypropenylphosphonate. An efficient, convergent synthesis of 2-cyclo-penten-1-ones",,10.1016/s0040-4039(01)95384-5,1979-01-01,0.5901381720225088
Tetrahedron,New total synthesis of eserine-type alkaloids via regioselective NaBH4-reduction of imides.,,10.1016/s0040-4039(00)91229-2,1975-01-01,0.590134056216141
Synthesis,"Ethyl 2,4-Dioxo-4-phenylbutyrate:A Versatile Intermediate for the Large-Scale Preparation of EnantiomericallyPure α-Hydroxy and α-Amino Acid Esters","Starting from ethyl 2,4-dioxo-4-phenylbutyrate, both enantiomers of six enantiomerically pure α-hydroxy and α-amino acid esters (homophenylalanine derivatives) were prepared on >100 g scale. The key step involves a Pt-cinchona catalyzed enantioselective hydrogenation followed by enrichment via crystallization. All derivatives are commercially available.",10.1055/s-2003-40885,2003-08-01,0.5901305978315586
Angewandte Chemie International Edition,From C<sub>1</sub> to C<sub>2</sub>: TMSCF<sub>3</sub> as a Precursor for Pentafluoroethylation,"Abstract A highly efficient copper‐mediated aromatic pentafluoroethylation method using TMSCF 3 as the sole fluoroalkyl source is described. The reaction proceeds by a key C 1 to C 2 process, that is, the generation of CuCF 3 from TMSCF 3 , followed by a subsequent spontaneous transformation into CuC 2 F 5 . Various aryl iodides were pentafluoroethylated with the TMSCF 3 ‐derived CuC 2 F 5 . This method represents the first practical and efficient method for pentafluoroethylation of aryl iodides using commercially available TMSCF 3 as a pentafluoroethyl precursor.",10.1002/anie.201807873,2018-08-23,0.5901275680066179
European Journal of Organic Chemistry,"Double Reductive Amination and Selective Strecker Reaction of a <scp>D</scp>‐Lyxaric Aldehyde: Synthesis of Diversely Functionalized 3,4,5‐Trihydroxypiperidines","Abstract A D ‐mannose‐derived aldehyde with the D ‐ lyxo configuration is a versatile key intermediate to functionally and stereochemically diversified piperidines. It allowed the synthesis of natural 3,4,5‐trihydroxypiperidines and new analogs through a double reductive amination strategy and the synthesis of novel 2‐cyanotrihydroxypiperidines through a highly regio‐ and diastereoselective Strecker reaction.",10.1002/ejoc.201200587,2012-06-15,0.5901234409188547
Organic Letters,"A Convergent Route to Geminal Difluorosulfides and to Functionalized Difluorothiochromans, a New Family of Organofluorine Compounds","The synthesis of the novel O-ethyl-S-(4-chlorophenylthio)difluoromethyl xanthate and its radical addition to various terminal alkenes are described. The geminal difluorosulfide adducts undergo closure onto the aromatic ring by further treatment with peroxide to furnish difluorothiochromans, a new family of organofluorine compounds.",10.1021/ol5002939,2014-02-14,0.5901078986499417
Tetrahedron,Cyclic trimer of 5-(aminomethyl)-2-furancarboxylic acid as a novel synthetic receptor for carboxylate recognition,,10.1016/s0040-4039(01)02367-x,2002-02-01,0.5901051384161532
Journal of Organic Chemistry,Stereoselective Synthesis of Chiral 4-(1-Chloroalkyl)-β-Lactams Starting from Amino Acids and Their Transformation into Functionalized Chiral Azetidines and Pyrrolidines,"Chiral short-chain alpha-chloroaldehydes were prepared starting from enantiomerically pure amino acids in a three-step approach, thus providing a practical synthetic alternative for known organocatalytic alpha-chlorination procedures. The latter aldehydes proved to be useful starting materials for the stereoselective Staudinger synthesis of (3S,4S)-4-[(1S)-1-chloroalkyl]azetidin-2-ones in high diastereomeric ratios and good overall yields, which were used as chiral building blocks for the preparation of a number of azetidines and pyrrolidines.",10.1021/jo101220q,2010-08-12,0.5900976898484129
Synthesis,"A Convenient Route to a Linear C<sub>18</sub>Carboxylic Acid Derivative Containing a Thiophene Ring in the Chain via a 9,10-Epithio-12-oxo Intermediate","All articles of this category Methyl ricinoleate ( 1 ) is oxidized to methyl 12-oxo- cis -9-octadecenoate ( 2 ) with chromic acid; epoxidation then affords methyl cis -9, 10-epoxy-12-oxooctadecanoate ( 3 ). Treatment of 3 with dimethylthioformamide in presence of trifluoroacetic acid gives a mixture of methyl cis -9,10-epithio-12-oxooctadecanoate ( 4 , 27%), methyl 5-hexylthiophene-2-octanoate ( 5 , 15%), and methyl 5 -hexylfuran-2-octanoate ( 6 , 9%) Compound 4 can be conveniently converted to 5 (83%) by refluxing with trifluoroacetic acid in 1,2-dichloroethane.",10.1055/s-1988-27607,1988-01-01,0.5900891821765245
Synlett,"Enantioselective Synthesis of α-Aminophosphonates via Organocatalytic Sulfenylation and [2,3]-Sigmatropic Sulfimide Rearrangement","β,γ-Unsaturated-α-aminophosphonates are prepared in enantiomerically enriched form via organocatalytic aldehyde α-sulfenylation/olefination followed by oxaziridine-mediated sulfimidation and sulfimide [2,3]-sigmatropic rearrangement. Subsequent N-deprotection and amino acid coupling are also accomplished.",10.1055/s-0030-1260309,2011-09-13,0.590087506280011
Tetrahedron,A novel synthesis of s-triazoloazines fused at the N2C3 bond of the triazole ring,,10.1016/s0040-4039(01)96026-5,1973-01-01,0.5900696407230878
Tetrahedron,A facile and novel route to the antigenic branched phosphoglycan of the protozoan Leishmania major parasite,,10.1016/j.tetlet.2004.01.155,2004-02-21,0.5900691776372134
Tetrahedron,"A practical process for large-scale synthesis of (S)-5-hydroxy-6-trans-8,11,14-cis-eicosatetraenoic acid (5-HETE)",,10.1016/0040-4039(81)80080-9,1981-01-01,0.5900686713387271
Tetrahedron,Indium trichloride catalyzed efficient one-pot synthesis of highly substituted furans,,10.1016/j.tetlet.2007.02.019,2007-02-10,0.5900634910513293
Journal of Organic Chemistry,"Total Syntheses of Allelopathic 4-Oxyprotoilludanes, Melleolides, and Echinocidins","Stereocontrolled total syntheses of allelopathic 4-oxyprotoilludane sesquiterpenes, melleolide, melleolide F, and echinocidins B and D were achieved. The curved 5/6/4 tricyclic system with an angular hydroxy group was built via three key transformations: (1) Me 3 Al-catalyzed [2 + 2] cycloaddition of a ketene silyl acetal with a propiolate, (2) reductive ring-opening of a cyclic hemiketal, and (3) the intramolecular Morita–Baylis–Hillman reaction. This synthetic route represents a new and reliable strategy to obtain protoilludanes with several oxy-functional groups.",10.1021/acs.joc.9b01589,2019-08-12,0.5900566310785498
Synlett,An Efficient and Practical Process for the Synthesis of Glimepiride,"A novel and simple approach to the synthesis of glimepiride is reported. It involves the preparation of a carbamate of 3-ethyl-4-methyl-1H-pyrrol-2(5H)-one, followed by its reaction with 4-(2-aminoethyl)benzenesulfonamide to produce the intermediate sulfonamide. This sulfonamide, upon reaction with phenyl (trans-4-methylcyclohexyl)carbamate, gave glimepiride. This process avoids the use of phosgene, isocyanates, or chloroformates. Furthermore, sulfonation of the aryl group was eliminated, rendering the product free of the impurities reported in earlier processes.",10.1055/s-0036-1590836,2017-08-17,0.5900561749320719
Tetrahedron,Addition of iodine thiocyanate to olefins a new synthesis of episulfides,,10.1016/s0040-4039(01)94101-2,1972-01-01,0.5900559034673497
Organic Letters,Total Synthesis of Resiniferatoxin Enabled by Photocatalytic Decarboxylative Radical Cyclization,"Resiniferatoxin ( 1 ) is a complex daphnane diterpenoid with a highly oxygenated 5/7/6-membered ABC-ring system. Here we report a new synthetic route to 1 that requires 27 steps from a starting d -ribose derivative. The carbon spacer and A-ring are sequentially attached to the C-ring by radical allylation and Stille coupling reactions, respectively. An Ir(III)-catalyzed photoinduced decarboxylative radical reaction then forged the sterically hindered bond between the tetra- and trisubstituted carbons to cyclize the central seven-membered B-ring.",10.1021/acs.orglett.1c04286,2022-01-19,0.5900557973100689
European Journal of Organic Chemistry,"Synthesis of 1,3,6‐Trisubstituted Azulenes Based on the 1‐Acyloxyazulene Scaffold","An efficient synthetic route to 1,3,6‐trisubstituted azulenes based on the 1‐acyloxyazulene scaffold was developed. The 1‐position in azulene was substituted in the ring‐formation step with a functionalized acyloxy group. Additionally, the 3‐ and 6‐positions of azulene were functionalized with versatile synthetic handles, a halogen atom and a formyl group.",10.1002/ejoc.201600962,2016-09-12,0.5900493187388657
Journal of Organic Chemistry,"A Highly Practical Synthesis of Sulfated Lewis X:  One-Pot, Two-Step Glycosylation Using “Armed/Disarmed” Coupling and Selective Benzoylation and Sulfation","In spite of the several attractive biological activities of the Le x, sLe x, and sulfated Le x derivatives, there are still limitations in their practical syntheses. One of the most difficult problems is the many steps required for their syntheses. Therefore, we investigated simple constructions of the Le x analogs and succeeded in establishing highly practical syntheses of the Le x and sulfated Le x analogs. Especially, the “armed/disarmed” method allowed the first synthesis of Le x derivatives by a one-pot, two-step glycosylation. This synthetic strategy could be an applicable and useful method for oligosaccharide constructions of Le x, sulfated Le x, and other derivatives.",10.1021/jo970076m,1997-10-01,0.5900477267510769
Synlett,"Palladium-Catalyzed Allylic Alkylation of Allyl Dienol Carbonates: Reactivity, Regioselectivity, Enantioselectivity, and Synthetic Applications","For the past several years, the group has focused on the development of useful synthetic tools and on executing creative and efficient routes to biologically active natural products. In this context, we recently applied the palladium-catalyzed decarboxylative allylic alkylation reaction to a new class of substrates, namely allyl dienol carbonates. This method allowed a particularly straightforward access to a wide variety of heterocycles, including 2,4-disubstituted-, 2,3,4- and 2,3,5-trisubstituted-, and 2,3,4,5-tetrasubstituted furans and pyrroles, starting from simple and readily available substrates. An asymmetric version of this method was also developed and applied to the synthesis of enantiomerically enriched butenolides and butyrolactones bearing all-carbon α- and β-quaternary stereogenic centers, respectively. This asymmetric transformation was eventually used as a key step in the total synthesis of two natural products: (–)-nephrosteranic acid and (–)-roccellaric acid. This account summarizes the results of our endeavors. 1 Introduction 2 Palladium-Catalyzed Decarboxylative Allylic Alkylation of Allyl Dienol Carbonates 2.1 Synthesis of Polysubstituted Furans 2.2 Synthesis of Polysubstituted Pyrroles 3 Asymmetric Palladium-Catalyzed Decarboxylative Allylic Alkylation of Allyl Dienol Carbonates 3.1 Synthesis of Enantiomerically Enriched Butenolides 3.2 Synthesis of Enantiomerically Enriched Furanones 3.3 Synthesis of Enantiomerically Enriched Butyrolactones 3.4 Total Syntheses of (–)-Nephrosteranic Acid and (–)-Roccellaric Acid 4 Conclusion",10.1055/s-0033-1338987,2013-10-18,0.5900442773081218
Angewandte Chemie International Edition,First Stereoselective Total Synthesis of FD‐594 Aglycon,"Stereocontrolled access to the hexacyclic core of FD-594 has been achieved. The key steps include the intramolecular S(N)Ar reaction for construction of the densely functionalized xanthone skeleton, the stereoselective lactone cleavage using a chiral nucleophile to induce the axial stereochemistry, and the SmI(2)-mediated pinacol cyclization for the stereocontrolled conversion of axially chiral biaryl dialdehyde into the corresponding trans diol.",10.1002/anie.200806338,2009-04-03,0.5900439160114733
Organic Process Research & Development,Process Improvements for the Preparation of Kilo Quantities of a Series of Isoindoline Compounds,"A series of isoindoline analogues with either an indazole (HMR 2934, HMR 2651) or benzisoxazole (HMR 2543) appendage were prepared for the proposed treatment of psychiatric disorders such as obsessive compulsive disorder and attention deficit disorder. The isoindoline compounds were prepared by reduction of the corresponding phthalimides with LiAlH 4 . One compound was not chiral, and the other two required an enantioselective synthesis. The key step for these optically active analogues involved the coupling by an S N 2 process of either a piperazynyl intermediate or a piperdinyl intermediate with methyl 3-benzyloxy-2-trifluoromethansulfonatopropionate. The products for these two analogues had >98% ee. Process improvements led to the multi-kilogram syntheses of each of these compounds.",10.1021/op020225p,2003-05-06,0.5900433271651482
Tetrahedron,Synthesis and cyclization of N-methyl-O-cinnamonylhydroxylamine and its bearing on Baldwin's rules for ring closure,,10.1016/s0040-4039(01)95117-2,1978-01-01,0.5900416255739185
Journal of Organic Chemistry,"Total Synthesis and Structural Reassignment of Aranorosinol A, Aranorosinol B, and EI-2128-1","Herein, we report a concise and collective total synthesis of three natural products aranorosinol A, aranorosinol B, and EI-2128-1 and also the known penicimutanolone. A unified strategy was conceived, which divergently accessed all four congeners within 9–11 steps (LLS) from a common intermediate. Bisoxirane-directed 1,2-addition was utilized as a key step to generate the desired configuration of the C 8 stereocenter of aranorosinol A and B, 28 years after their first isolation, and these were both assigned as S configurations, while the C 4′ and C 6′ configurations of EI-2128-1 were both determined to be R, R -configurations.",10.1021/acs.joc.0c00028,2020-02-20,0.5900359995393872
Journal of Organic Chemistry,Convergent Highly Stereoselective Preparation of the C12−C24 Fragment of Macrolactin A,"The convergent synthesis of the C12-C24 fragment (lower part) of macrolactin A is described. The adapted strategy allowed building up the lower moiety by the assembly of three key intermediates via organometallic addition. One hydroxylic stereogenic center was introduced by the application of chiral sulfoxides methodology on fragment C19-C24. The preparation of the versatile 1,3-anti diol synthon C12-C16 was achieved via opening of chiral epoxide and subsequent oxidation to a hydroxy ketone. Finally, reductive elimination of the appropriate allylic dibenzoate with Na/Hg introduced directly the C16-C19 (E,E)-diene unit, in a highly efficient stereoselective fashion.",10.1021/jo049556l,2004-06-25,0.5900348654524744
Organic Letters,Asymmetric Synthesis of the Tricyclic Core of <i>Calyciphylline</i> A-Type Alkaloids via Intramolecular [3 + 2] Cycloaddition,"Asymmetric synthesis of the [5-6-7] tricyclic system common to the Calyciphylline A-type alkaloids is reported, featuring Overman rearrangement, Heck cyclization, intramolecular [3 + 2] cycloaddition, diastereoselective hydrogenation, and Claisen rearrangement as strategic events. The approach is capable of installing the crucial carbonyl functionality as well as multiple stereogenic centers within a congested polycyclic ring skeleton.",10.1021/ol403609c,2014-02-07,0.5900331579347028
Synthesis,"Synthesis of Novel 3,19-Dihydroxyjolkinolides and Related Derivatives Starting from Andrographolide","The jolkinolides are a series of naturally occurring ent -abietane diterpenes with potent antitumor activity, which have been isolated from the genus Euphorbia . We describe the first method for the total synthesis of 3,19-dihydroxyjolkinolide and its derivatives. The strategy for the synthesis of 3,19-dihydroxyjolkinolide A has 12 steps with an overall yield of 4.3%. The synthesized compounds were evaluated for their antitumor activity in nine kinds of tumor cell lines.",10.1055/s-0035-1561598,2016-05-03,0.5900312808326428
Angewandte Chemie International Edition,Versatile Synthetic Route to Cycloheximide and Analogues That Potently Inhibit Translation Elongation,"Cycloheximide (CHX) is an inhibitor of eukaryotic translation elongation that has played an essential role in the study of protein synthesis. Despite its ubiquity, few studies have been directed towards accessing synthetic CHX derivatives, even though such efforts may lead to protein synthesis inhibitors with improved or alternate properties. Described here is the total synthesis of CHX and analogues, and the establishment of structure-activity relationships (SAR) responsible for translation inhibition. The SAR studies aided the design of more potent compounds, one of which irreversibly blocks ribosomal elongation, preserves polysome profiles, and may be a broadly useful tool for investigating protein synthesis.",10.1002/anie.201901386,2019-02-26,0.5900236763847535
Synthesis,Stereoselective Synthesis of (-)-Galantinic Acid,An efficient and highly concise synthesis of (-)-galantinic acid has been achieved using an asymmetric allylation reaction of Garner’s aldehyde.,10.1055/s-0030-1258431,2011-02-10,0.5900233116626081
Tetrahedron,Prostaglandin synthesis. II. A novel resolution of aldehyde and ketone intermediates,,10.1016/s0040-4039(01)96034-4,1973-01-01,0.590014911244286
Journal of Organic Chemistry,Synthesis of Coumestan Derivatives via FeCl<sub>3</sub>-Mediated Oxidative Ring Closure of 4-Hydroxy Coumarins,"A concise and efficient approach to the syntheses of coumestan analogues has been developed. The underpinning strategy involves a FeCl(3)-mediated direct intramolecular oxidative annellation of 4-hydroxy-3-phenyl-2H-chromen-2-one derivatives. Utilizing this synthetic protocol, a variety of coumestan derivatives were conveniently obtained from readily available reagents.",10.1021/jo2000644,2011-03-14,0.5900135158364302
Tetrahedron,An efficient and stereoselective route to 1-deoxy-5-hydroxy sphingosine analogues,,10.1016/j.tetlet.2009.01.024,2009-01-14,0.5900120729533453
Angewandte Chemie International Edition,"Synthesis of (+)‐Darwinolide, a Biofilm‐Penetrating Anti‐MRSA Agent","Darwinolide, a recently identified marine natural product from the Antarctic sponge Dendrilla membranosa, was previously shown to exhibit promising activity against the biofilm phase of methicillin-resistant Staphylococcus aureus. Its challenging tetracyclic rearranged spongian diterpenoid structure links a trimethylcyclohexyl subunit to a seven-membered core with two fused tetrahydrofuran units. Herein, we describe the first synthesis of (+)-darwinolide, which features a convergent aldol fragment coupling, an Ireland-Claisen rearrangement, and an organocatalytic desymmetrization as the key steps. Our results provide a foundation for the development of novel antibiofilm-specific antibiotics.",10.1002/anie.201813142,2018-11-19,0.5900082915719501
Tetrahedron,Intramolecular biaryl coupling: Asymmetric synthesis of the chiral b-ring diol unit of pradimicinone,,10.1016/s0040-4039(00)94359-4,1990-01-01,0.5900079548765766
Journal of Organic Chemistry,"Synthesis of 5-Amino-2,5-dihydro-1<i>H</i>-benzo[<i>b</i>]azepines Using a One-Pot Multibond Forming Process","Rapid access to allylic trichloroacetimidates bearing a 2-allylaminoaryl group from readily available 2-iodoanilines combined with a one-pot multibond forming process has allowed the efficient synthesis of a series of 5-amino-2,5-dihydro-1H-benzo[b]azepines. The potential of these compounds as synthetic building blocks was demonstrated by the preparation of a late-stage intermediate of the hyponatremia agent, mozavaptan.",10.1021/acs.joc.6b01357,2016-07-14,0.5900038217103011
Tetrahedron,"Syntheses of chiral oxazolo[2,3-a]tetrahydroisoquinoline and its asymmetric alkylation. Synthesis of (S)-(−)- and (R)-(+)-sa1solidines",,10.1016/s0040-4039(00)88483-x,1988-01-01,0.5900018968577742
Tetrahedron,Synthesis of carbazoles by cyclizative condensation of the methyl group of 2-methylindoles,,10.1016/s0040-4039(00)70912-9,1962-06-01,0.5899932311507279
Organic Letters,Synthesis of 5- and 6-Carboxy-X-rhodamines,"An efficient route is reported to 5- and 6-carboxy-X-rhodamines (compounds 1 and 2) that contain multiple n-propylene or gamma,gamma-dimethylpropylene groups bridging terminal nitrogen atoms and the central xanthene core. Gram quantities of these dyes are synthesized from inexpensive starting materials. The isolated products are activated by selective transformation of the carboxylic acid group into N-hydroxysuccinimidyl esters in situ and then conjugated with an amino group of a molecule of interest.",10.1021/ol801904k,2008-10-07,0.5899874169266824
Journal of Organic Chemistry,Biomimetic Synthesis of Chaxine and its Related Compounds,"The highly oxidized natural products chaxine B and BB have been synthesized from ergosterol in eight steps according to a route inspired by their proposed biosynthesis; key steps were an oxidative cascade from a furan intermediate to an enol ester using m -chloroperbenzoic acids (MCPBA), followed by diastereoselective epoxidation and acyloxy migration. This concise synthesis resulted in the revision of the structures of chaxine B and its naturally occurring analogs and syntheses of the unnatural analogues of these natural products for biological investigations.",10.1021/acs.joc.9b03482,2020-02-24,0.5899864404318691
Synlett,"Enantioselective Synthesis of a Bicyclo[3.1.0]hexane A-Ring Synthon for 1α, 25-Dihydroxyvitamin D3","All articles of this category A bicyclo[3.1.0]hexane A-ring synthon of 1α, 25-dihydroxyvitamin D 3 has been prepared starting with ( S )-malic acid. The key step in the sequence involves a highly diastereoselective intermolecular cyclopropanation reaction of a chiral cyclopentenone. This method avoids using a selenium oxidation to introduce the 1α-hydroxy group. 1α, 25-dihydroxyvitamin D 3 - diastereoselective cyclopropanation - malic acid - chiral cyclopentenone",10.1055/s-1995-5097,1995-08-01,0.5899804571121495
Synlett,Asymmetric Oxidopyrylium-Alkene [5+2] Cycloaddition: Synthesis of Enantiopure oxa-Bridged Bicyclo[5.4.0]undecanes,A facile route to the synthesis of enantiomeric oxa-bridged bicycloadducts 9 and 18 has been developed employing an intramolecular [5+2] cycloaddition of 3-oxidopyrylium with unsaturated sugars.,10.1055/s-2003-42113,2003-01-01,0.5899713927644361
Organic Letters,"Reagent-Controlled α-Selective Dehydrative Glycosylation of 2,6-Dideoxy Sugars: Construction of the Arugomycin Tetrasaccharide","The first synthesis of the tetrasaccharide fragment of the anthracycline natural product Arugomycin is described. A reagent controlled dehydrative glycosylation method involving cyclopropenium activation was utilized to synthesize the α-linkages with complete anomeric selectivity. The synthesis was completed in 20 total steps, and in 2.5% overall yield with a longest linear sequence of 15 steps.",10.1021/acs.orglett.0c01153,2020-04-13,0.5899678954994598
Journal of Organic Chemistry,"Stereoselective Approach to<i>cis</i>-2,3-Disubstituted Piperidines via Reduction of<i>N</i>-Acyliminium Ion Intermediate: Enantioselective Synthesis of (+)-(2<i>S</i>,3<i>S</i>)-CP-99,994","A very simple and efficient stereoselective approach to cis-2,3-disubstituted piperidines via the reduction of N-acyliminium ion intermediates is described. Application of this methodology is exemplified by the enantioselective total synthesis of (+)-(2S,3S)-CP-99,994.",10.1021/jo302181k,2012-11-27,0.5899557402741556
Tetrahedron,Dispiroketals in synthesis (Part 5): A new opportunity for oligosaccharide synthesis using differentially activated glycosyl donors and acceptors,,10.1016/s0040-4039(00)61375-8,1993-01-01,0.5899538691767788
European Journal of Organic Chemistry,Synthesis and Rearrangement of Cage [4.3.2]Propellanes that Contain a Spiro Linkage,"Rearranged cage ketones 6a and 6b are reported in eight linear synthetic steps from 2,5‐dimethoxybenzaldehyde 9 without the use of protecting groups. In this regard, Diels–Alder reaction, [2+2]photocycloaddition and Lewis acid promoted rearrangement with BF 3 · OEt 2 were used as key steps. Surprisingly, during the ring expansion process with Lewis acid, solvent incorporation occurred. This rearrangement approach has provided difficult complex targets through non‐obvious synthetic routes. The rearrangement process demonstrated here opens up a new synthetic strategy to interesting and unusual cage molecules.",10.1002/ejoc.201700617,2017-06-16,0.5899516660503642
Tetrahedron,"A novel approach for the synthesis of the peripheral benzodiazepine receptor ligand, PK11195",,10.1016/j.tetlet.2007.07.203,2007-08-03,0.5899421533782843
Tetrahedron,"Synthesis of ( S )-3-amino-benzo[ b ][1,4]oxazepin-4-one via Mitsunobu and S N Ar reaction for a first-in-class RIP1 kinase inhibitor GSK2982772 in clinical trials",,10.1016/j.tetlet.2017.05.001,2017-05-03,0.5899339741819302
Angewandte Chemie International Edition,A Concise Total Synthesis of (−)‐Himalensine A,"The daphniphyllum alkaloids are a structurally fascinating and remarkably diverse family of natural products. General strategies for the chemical synthesis of their challenging architectures are highly desirable for efficiently accessing these intriguing alkaloids and addressing their pharmaceutical potential. Herein, a concise strategy designed to provide general and diversifiable access to various daphniphyllum alkaloids is described and utilized in the asymmetric synthesis of (-)-himalensine A, which was accomplished in 14 steps. Key features of this strategy include a Cu-catalyzed nitrile hydration, a Heck reaction to construct the challenging 2-azabicyclo[3.3.1]nonane motif, a Meinwald rearrangement reaction, six, pot-economic reactions, and the minimal use of protecting groups, which significantly improved the overall synthetic efficiency.",10.1002/anie.201902908,2019-04-08,0.5899290711393279
European Journal of Organic Chemistry,"A Short Total Synthesis of the Alkaloids Piperolactam C, Goniopedaline, and Stigmalactam","Abstract The total synthesis of the polyalkoxylated alkaloids piperolactam C, goniopedaline and stigmalactam by combinatorial metalation/cyclization strategies has been achieved. The synthetic route involved the preliminary construction of the polyalkoxylated isoindolinone template by Parham’s technique. Benzylic lactam deprotonation allowed connection of a hydroxybenzyl appendage, and the synthesis of the target natural products was completed by subsequent E1cB elimination, radical cyclization and final deprotection. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2003)",10.1002/ejoc.200390177,2003-03-01,0.5899212511326772
Angewandte Chemie International Edition,Total Synthesis of Peribysin E Necessitates Revision of the Assignment of its Absolute Configuration,"The right way round: Peribysin E, a naturally occurring adhesion inhibitor, has been synthesized and, as a result, its absolute configuration reassigned. The natural and nonnatural enantiomers can be reached starting from (R)- or (S)-carvone, respectively. A key step is the ring contraction of 1 to 2 (see scheme, TBS=tert-butyldimethylsilyl, TES=triethylsilyl).",10.1002/anie.200604308,2007-01-19,0.5899164714321173
Synlett,Glycerophosphoinositols: Total Synthesis of the First Fluorescent Probe Derivative,"The first fluorescent glycerophosphoinositol probe was synthesized in moderate good yield (37%). The total synthesis applied a convergent synthetic strategy involving two successive coupling reactions between the three key moieties: myo -inositol, glycerol, and NBD-aminohexanoic acid.",10.1055/s-0034-1378537,2014-07-31,0.5899159606449748
Organic Letters,Synthesis of the Himandrine Skeleton,"The hexacyclic himandrine skeleton 5, which is present in the most complex alkaloids of the tropical rain forest tree Galbulimima belgraveana, has been prepared for the first time. The synthesis begins from the known [3.2.1]benzobicyclooctene intermediate 10. Key steps include a Diels-Alder cycloaddition, Curtius rearrangement, Birch reduction, an intramolecular nucleophilic amination, and a palladium-mediated alkene amination. [reaction: see text]",10.1021/ol036308n,2004-02-04,0.5899114932365646
Organic Letters,Total Synthesis of (±)-Kellermanoldione: Stepwise Cycloaddition of a Functionalized Diene and Allenoate,"The total synthesis of the diterpene kellermanoldione 1 is reported. Stepwise [4 + 2] cycloaddition of the ketal diene 8 and the allenoate 3 afforded the exo adduct 10x as the major product. It was converted into 1 via six steps, among them a key nonconjugative hydrolysis of a gamma-methylene silyl enol ether.",10.1021/ol901455q,2009-08-05,0.5899107450883496
European Journal of Organic Chemistry,"Complementary and Stereodivergent Approaches to the Synthesis of 5‐Hydroxy‐ and 4,5‐Dihydroxypipecolic Acids from Enantiopure Hydroxylated Lactams","Abstract We describe two complementary and stereodivergent routes, from commercially available and inexpensive starting materials, for the synthesis of 4,5‐dihydroxy‐ and 5‐hydroxypipecolic acids based on the chemistry of lactam‐derived enol phosphates. The synthesis of the 4,5‐ cis ‐4,5‐dihydroxypipecolic acids required the preparation from 2‐deoxy‐ D ‐ and ‐ L ‐ribose of the enantiopure cis ‐(4 S ,5 R )‐ and ‐(4 R ,5 S )‐4,5‐dihydroxy‐δ‐valerolactam, respectively. These new chiral synthons are potentially useful for the synthesis of other natural products. The key step is the Pd‐catalyzed methoxycarbonylation reaction of the enol phosphates generated from these lactams. This reaction provided enecarbamate esters that were easily converted by stereoselective reduction to the target compounds. The synthesis of the 4,5‐ trans ‐4,5‐dihydroxypipecolic acid, as well as of 5‐hydroxypipecolic acids, was realized from a known ( S )‐5‐hydroxy‐δ‐valerolactam derivative and, for the dihydroxylated compound, required a highly stereoselective allylic bromination reaction of the enecarbamate ester obtained by methoxycarbonylation of the enol phosphate. The preparation of the (4 R ,5 S ) enantiomer of the cis ‐4,5‐dihydroxy‐δ‐valerolactam from 2‐deoxy‐ L ‐ribose, alongside the fact that ( R )‐5‐hydroxy‐δ‐valerolactam can be prepared from ( R )‐(–)‐γ‐hydroxymethyl‐γ‐butyrolactone, means our approach allows for the synthesis of all stereoisomers of these compounds, which can be employed as conformationally constrained scaffolds in drug discovery.",10.1002/ejoc.201201429,2013-01-21,0.5899051642719283
Journal of Organic Chemistry,A Practical Synthesis of Kifunensine Analogues as Inhibitors of Endoplasmic Reticulum α-Mannosidase I,"[reaction: see text] A practical synthesis of the potent class I alpha-mannosidase inhibitor kifunensine (1) beginning from the inexpensive and readily available starting material L-ascorbic acid (15) is described. The protected amino-alcohol ((2R,3R,4R,5R)-5-amino-2,3:4,6-diisopropylidenedioxyhexanol, 11) served as a key intermediate from which several N-1 substituted kifunensine analogues (including N-methyl, N-cyclohexyl, and N-bis(hydroxymethyl)methyl) and 2-desoxakifunensine analogues (including N-H and N-methyl) were prepared and screened for inhibition of human endoplasmic reticulum alpha-mannosidase I (ER Man I) and mouse Golgi alpha-mannosidase IA (Golgi Man IA). In addition, several pseudodisaccharide kifunensine analogues in which a mannose residue was tethered to N-1 of kifunensine via a two-, three-, or four-carbon linker and an affinity-bound kifunensine analogue were also prepared and evaluated for biological activity. While the synthesized N-1 kifunesine analogues were found to be less potent inhibitors of Class I alpha-mannosidases than kifuensine itself, the bis(hydroxymethyl)methylkifunensine analogue 6 was shown to selectively inhibit ER Man I over Golgi Man IA.",10.1021/jo0516382,2005-11-01,0.5898967622983046
Synlett,Formal Asymmetric Synthesisof (-)-Aphanorphine via Ring-Closing MetathesisReaction,"We have developed an asymmetric route to (-)-aphanorphine from O-Me-d-tyrosine methyl ester hydrochloride salt, available from d-tyrosine in four steps. The tricyclic framework of (-)-aphanorphine was assembled stereoselectively by intramolecular Friedel-Crafts reaction of the corresponding bicyclic precursor, which was in turn generated via ring-closing metathesis reaction.",10.1055/s-0028-1083498,2008-10-15,0.5898856791917332
Angewandte Chemie International Edition,A Flexible Synthesis of Polypropionates via Diastereodivergent Reductive Ring‐Opening of Trisubstituted Secondary Glycidols,"Abstract Polypropionates, characterized by their alternating sequence of stereocenters bearing methyl‐ and hydroxy‐groups, are structurally diverse natural products of utmost importance. [1] Herein, we introduce a novel concept approach towards polypropionate synthesis featuring a diastereodivergent reductive epoxide‐opening as a key step. Readily available and stereochemically uniform trisubstituted sec‐glycidols serve as branching points for the highly selective synthesis of all isomers of polypropionate building blocks with three or more consecutive stereocenters. Stereodiversification is accomplished by an unprecedented mechanism‐control over the stereochemically complementary modification of the epoxide's tertiary C‐atom with excellent control of regio‐ and stereoselectivity. Since our method is not only suited for the preparation of specific targets but also for compound libraries, it will have a great impact on polypropionate synthesis.",10.1002/anie.202317525,2023-12-18,0.5898837611664471
Tetrahedron,"Synthesis of 1,7-diamino-1,2,6,7-tetradeoxy-2,6-imino-D-glycero-D-ido-heptitol by intramolecular amination of aziridine ring",,10.1016/s0040-4039(97)10356-2,1997-12-01,0.5898784395439736
Synlett,Synthesis of <i>N</i>-Aminoindole Ureas from Ethyl 1-Amino-6-(trifluoromethyl)-1<i>H</i>-indole-3-carboxylate,"All articles of this category Two routes to the synthesis of ethyl 6-(trifluoromethyl)-1 H -indole-3-carboxylate are described. N -Amination of this key intermediate with O -(diphenylphosphinyl)hydroxylamine and subsequent reactions with aryl isocyanates, using pyridine as solvent, gave the corresponding N -aminoindole ureas 1 - 4 in good yields. aminations - indoles - cyclizations - urea formation - isocyanates",10.1055/s-2001-10784,2001-12-31,0.5898776464042721
Journal of the American Chemical Society,Total Synthesis of Spinosyn A. 2. Degradation Studies Involving the Pure Factor and Its Complete Reconstitution,"A total synthesis of natural levorotatory spinosyn A ( 1 ) has been achieved. The first objective, to confirm the absolute configurational assignment of tricyclic ketone 2 prepared earlier, was accomplished by oxidative degradation of the macrocyclic lactone ring in 1 . The route began with the implementation of a four-step one-pot process that resulted in the efficient conversion of 6 into 18 . A combination of periodate cleavage and peracid oxidation events then led to 2 . In the reconstruction phase, a Pd-catalyzed coupling of a vinylstannane with an acid chloride reestablished the great majority of the structure in an enantiocontrolled manner. Once macrolactonization had been effected, the 2,3,4-tri- O -methylrhamnose unit was introduced first with exceptionally good stereocontrol. The final glycosidation, which involved a 2-mercaptopyrimidine derivative of d -forosamine, was met with an expectedly diminished percentage of the desired β-anomer.",10.1021/ja974010k,1998-03-01,0.5898761963119408
Journal of Organic Chemistry,Synthesis of 1-Arylmethyl-2-(cyanomethyl)aziridines and Their Ring Transformation into Methyl<i>N</i>-(2-Cyanocyclopropyl)benzimidates,"1-Arylmethyl-2-(cyanomethyl)aziridines were prepared in high yields from the corresponding 2-(bromomethyl)aziridines upon treatment with potassium cyanide in DMSO. Ring opening of the aziridine moiety with N-chlorosuccinimide in CCl4 and subsequent treatment of the thus formed 4-chloro-3-(N-chloro-N-(alpha,alpha-dichlorobenzyl)amino)butanenitriles with sodium methoxide in methanol resulted in novel methyl N-(2-chloro-1-(cyanomethyl)ethyl)benzimidates, although in low yields. The latter gamma-chloro nitriles were smoothly converted into methyl N-(2-cyanocyclopropyl)benzimidates as precursors of biologically relevant beta-ACC derivatives through a 1,3-cyclization protocol by reaction with potassium tert-butoxide in THF.",10.1021/jo060425p,2006-05-01,0.5898642501984278
Synthesis,"A Short Synthesis of Optically Active γ,γ-Dimethylallyltryptophan (DMAT)","All articles of this category A short synthesis (4 steps) of optically active γ,γ-dimethylallyltryptophan ( 1 , DMAT) was accomplished from N α - tert -butoxycarbonyl(Boc)-4-(3-hydroxy-3-methyl-1-buten-1-yl)-1-tosyl-tryptophan methyl ester ( 5 ) prepared by Heck reaction of N α -Boc-4-bromo-1-tosyltryptophan methyl ester ( 4 ) with 1,1-dimethylallylalcohol. 4-bromotryptophan - γ,γ-dimethylallyltryptophan (DMAT) - optically active synthesis - Heck reaction",10.1055/s-2000-6246,2000-01-01,0.5898601660995488
Tetrahedron,"A new chiral glycine synthon. Synthesis, x-ray structure of (−).(2S,4R)-2-ethoxycarbonyl-4-phenyl-1,3-oxazolidine and diastereoselective nucleophilic ring opening to (R)-ethyl α-amino carboxylates.",,10.1016/s0040-4039(00)61274-1,1992-08-01,0.589858933988651
Tetrahedron,Efficient procedure for the synthesis of erythro and threo furanoid glycals from 2-deoxyribose,,10.1016/s0040-4039(00)73538-6,1994-07-01,0.5898566598962013
Synthesis,An Efficient Procedure for the Hantzsch Dihydropyridine Synthesis,,10.1055/s-1983-30505,1983-01-01,0.5898566598962013
Journal of Organic Chemistry,Synthetic Study of Kosinostatin Aglycon: Synthesis of the ABCDEFG Ring Skeleton,"High Resolution Image Download MS PowerPoint Slide A synthetic method for the CDEFG substructure of kosinostatin was developed using the cyclization of the di- para -nosyl 3-(2-hydroxyethyl)pyrrolidin-2-imine derivative. The key to the success of this cyclization was the choice of the para -nosyloxy ( p -NsO) group as the leaving group. This selection enabled the cyclization to proceed under mild reaction conditions, leading to the first construction of a kosinostatin-type scaffold. The method was further applied to the synthesis of the ABCDEFG ring of kosinostatin aglycon.",10.1021/acs.joc.5c00886,2025-06-18,0.5898552148666641
Synlett,"A Practical, Large-Scale Synthesis of Pyrene-2-Carboxylic Acid",Pyrene-2-carboxylic acid is a versatile intermediate for introducing the unusual 2-pyrenyl unit into functional organic molecules. A classical preparation for this molecule has been revised and improved to give a robust and efficient three-step process. The method has been applied on a multigram scale to give pyrene-2-carboxylic acid in >70% overall yield from pyrene.,10.1055/s-0034-1379026,2014-10-02,0.5898520848726001
Tetrahedron,Diastereoselective routes to and ethyl 1-azabicyclo[2.2.1] hept-3-YL carboxylates,,10.1016/s0040-4039(00)92055-0,1991-02-01,0.5898457302304673
Synthesis,"Chiral 2,4,6-Trihydroxycyclohexanones as Potent Building Blocks: A Convenient Method for the Preparation of Enantiomerically Pure Acyclic 1,3-Diols","The chiral triply silyl-protected 2,4,6-trihydroxycyclohexanones 1a and 1c were shown to be excellent precursors for the synthesis of chiral acyclic 1,3-diols. A three-step sequence provided easy access to syn- and anti-1,3-diols 4 (69-75% over three steps).",10.1055/s-2005-872141,2005-08-04,0.5898442151376571
Tetrahedron,"New synthesis of substituted biphenyls, biaryls, and terphenyls from arylidenemalonodinitriles, ethyl pyruvate, and malonodinitrile",,10.1016/s0040-4039(00)94686-0,1990-01-01,0.5898415131603728
Synthesis,"A Convenient Approach to the Synthesis of ω-Heterocyclic Amino Acids from Carboxy Lactams through Ring-Chain Transformation; Part 1: Synthesis of (2<i>S</i>)-/(2<i>R</i>)-2-Amino-4-(1-aryl-/1,5-diaryl-1<i>H</i>-pyrazol-3-yl)butyric Acid","A general method is reported for the synthesis of ω-heterocyclic α-amino acids, which involves preparation of enaminone intermediates from thiolactams, followed by reaction with dinucleophiles, resulting in a single-step condensation and ring-chain transformation to the desired ω-heterocyclic α-amino acids after deprotection of amine and carboxylic group. The reaction steps preserve the chirality of the parent-substituted lactam. The method is illustrated by the synthesis of (2S)- and (2R)-2-amino-4-(1-aryl-/1,5-diaryl-1H-pyrazol-3-yl)butyric acids.",10.1055/s-2005-872166,2005-08-12,0.5898371628327743
European Journal of Organic Chemistry,"Total Synthesis of a Pyrrole Lactone Alkaloid, Longanlactone","Abstract The first asymmetric total synthesis of the natural pyrrole lactone longanlactone has been achieved. The key reactions, a Barbier propargylation and a Paal–Knorr pyrrole synthesis, have provided easy access to the target natural product from L ‐aspartic acid in six steps and 31 % overall yield. The C‐4 epimer of the natural product and propionyllonganlactone have also been prepared by this strategy.",10.1002/ejoc.201402563,2014-08-15,0.5898361514053856
Synlett,Isosaccharino- and Glucosaccharino-Lactones as Chirons for the Syntheses of Natural Compounds and Analogs of Biological Relevance,"All articles of this category α-D-lsosaccharino- and α-glucosaccharino-1,4-lactones, readily obtained by alkaline treatment of abundant sugars, represent versatile chiral non-racemic starting materials for the syntheses of molecules containing a tertiary alcohol function. Their usefulness is undoubtedly illustrated by the numerous regio- and stereocontrolled syntheses of biologically relevant molecules such as antibiotics, anticancer agents, pheromones and nucleosides. 1. Introduction 1.1. Access from natural sugars 1.2. Mechanism of Formation and Synthesis 2. α-D-Isosaccharino- 1,4-lactone as starting material for 2.1. Subunits of antibiotics or antibiotic synthesis 2.2. Frontalin pheromone synthesis 2.3. Ring A of the anthracyclinone incorporation 2.4. C -branched-chain nucleoside analogs 2.5. Miscellaneous 3. α-D-Glucosaccharino- 1,4-lactone as starting material for: 3.1. Synthesis of antibiotic subunits 3.2. Total synthesis of AK-toxin II 3.3. Incorporation of anthracyclinones in ring A 3.4. C -branched-chain nucleoside analogs",10.1055/s-1994-22839,1994-01-01,0.5898351451959496
Journal of Organic Chemistry,An improved chemical synthesis of racemic phycocyanobilin di methyl ester,,,1978-07-28,0.5898321517553963
Tetrahedron,The development of hydrazide γ-turn mimetics,,10.1016/s0040-4039(97)01664-x,1997-10-01,0.5898278052111535
Tetrahedron,Enantioselective formal total synthesis of (−)-trachyspic acid,,10.1016/j.tetlet.2009.01.057,2009-01-20,0.5898277463725161
Tetrahedron,Total and formal enantioselective synthesis of lyngbic acid and hermitamides A and B,,10.1016/j.tetlet.2006.05.078,2006-06-07,0.5898277463725161
Synthesis,"Diastereoselective Synthesis of the<i>C</i> <sub>2</sub>-Symmetric 2,3-Diaminotetralin via Electrophilic Amination","All articles of this category Starting from the N,N -dibenzyl protected ß-amino acid 3 a synthesis of the C 2 -symmetric racemic 2,3-diaminotetralin ( 4 ; 2,3- diamino-1,2,3,4-tetrahydronaphthalene) is reported. The key step of the procedure is a highly stereocontrolled electrophilic amination by dibenzyl azodicarboxylate.",10.1055/s-1994-25629,1994-01-01,0.5898263304995633
Tetrahedron,Routes to HIV-integrase inhibitors: efficient synthesis of bicyclic pyrimidones by ring expansion or amination at a benzylic position,,10.1016/j.tetlet.2008.10.119,2008-10-31,0.5898219825513535
Angewandte Chemie International Edition,Eine Carben-Komplex-Route zu Vitamin E,,10.1002/anie.198310450,1983-09-01,0.5898198130488825
Angewandte Chemie International Edition,Total Syntheses of Bisdehydroneostemoninine and Bisdehydrostemoninine by Catalytic Carbonylative Spirolactonization,The first total syntheses of the stemona alkaloids bisdehydroneostemoninine and bisdehydrostemoninine in racemic forms have been achieved. The synthetic strategy features a novel palladium-catalyzed carbonylative spirolactonization of a hydroxycyclopropanol to rapidly construct the oxaspirolactone moiety. It also features a Lewis acid promoted tandem Friedel-Crafts cyclization and lactonization to form the 5-7-5 tricyclic core of the target stemona alkaloids.,10.1002/anie.201809114,2018-09-19,0.5898190789793318
Organic Letters,Synthesis of the Trisaccharide Portion of the Immunologic Adjuvant QS-21A via Sulfonium-Mediated Oxidative and Dehydrative Glycosylation,[see structure]. The first synthesis of the trisaccharide fragment of the potent immunologic adjuvant QS-21A is reported. The key steps involve the application of sulfonium-mediated oxidative and dehydrative glycosidic couplings to construct the anomeric linkages in a short and convergent assembly of the branched trisaccharide.,10.1021/ol015651u,2001-05-11,0.5898081671792299
Angewandte Chemie International Edition,An Expedient Total Synthesis of Chivosazole F: an Actin‐Binding Antimitotic Macrolide from the Myxobacterium <i>Sorangium Cellulosum</i>,"A unified strategy for the chemical synthesis of the chivosazoles is described. This strategy is based on two closely related approaches involving the late-stage installation of the isomerization-prone (2Z,4E,6Z,8E)-tetraenoate motif, and an expedient fragment-assembly procedure. The result is a highly convergent total synthesis of chivosazole F through the orchestration of three mild Pd/Cu-mediated Stille cross-coupling reactions, including the use of a one-pot, site-selective, three-component process, in combination with controlled installation of the requisite alkene geometry.",10.1002/anie.201610636,2016-11-29,0.5898075886763309
Tetrahedron,Synthesis of novel 1-N-iminosugars from chiral nonracemic bicyclic lactams,,10.1016/j.tetlet.2004.04.121,2004-05-11,0.5898030027708515
Angewandte Chemie International Edition,Enantioselective Total Synthesis of Marine Diterpenoid Clavulactone,"The key steps in the synthesis of clavulactone are formation of an enantiopure cyclopentane precursor by epoxide rearrangement and intramolecular carbonyl-ene reaction, construction of the 3,4-dihydro-2H-pyran ring by intermolecular hetero-Diels-Alder reaction, closure of the eleven-membered ring, and finally generation of the lactone functionality by chemoselective allylic C(sp(3))-H oxidation.",10.1002/anie.201201369,2012-05-29,0.589800247243382
Angewandte Chemie International Edition,Catalytic Enantioselective Synthesis of Planar Chiral Pillar[5]arenes via Asymmetric Sonogashira Coupling,"As a novel type of macrocycles with attractive planar chirality, pillar[5]arenes have gained increasing research interest over the past decades, enabling their widespread applications in diverse fields such as porous materials, molecular machines, and chiral luminescence materials. However, the catalytic methodology towards the enantioselective synthesis of planar chiral pillar[5]arenes remains elusive. Here we report a novel method for the enantioselective synthesis of planar chiral pillar[5]arenes via asymmetric Sonogashira coupling, giving access to a wide range of highly functionalized planar chiral pillar[5]arenes, including both homo- and hetero-rimmed ones, with excellent enantioselectivities. Attractively, the resultant planar chiral pillar[5]arenes show great potential for widespread use in many areas such as chiral luminescent materials. This work not only enables the successful synthesis of planar chiral pillar[5]arenes with abundant structural and functional diversity as key building blocks for practical applications but also enriches the asymmetric cross-coupling methodologies in organic synthetic chemistry.",10.1002/anie.202415190,2024-09-11,0.5897979421974483
European Journal of Organic Chemistry,Synthesis of Substituted Benzyl Homo‐<i>C</i>‐Ribonucleosides and ‐Nucleotides as Carba Analogues of Phosphoribosylanthranilate,"Abstract New 2‐substituted benzyl C ‐ribonucleosides and ‐nucleotides were designed as carba analogues of phosphoribosylanthranilate, a key intermediate in tryptophan biosynthesis. The synthesis was based on the preparation of TBS‐protected 2‐bromobenzyl C ‐ribonucleoside 4a by addition of (2‐bromobenzyl)magnesium bromide to ribonolactone followed by reduction and subsequent functional group transformations. Pd‐catalyzed hydrogenation, cross‐couplings, amination or hydroxylation, as well as lithiation followed by reaction with CO 2 and amidations, gave a large series of 2‐alkyl‐, 2‐(het)aryl, 2‐amino, 2‐hydroxy, 2‐carboxy and 2‐carbamoyl derivatives that were deprotected to afford free homo‐ C ‐ribonucleosides. Some of the title nucleosides were converted to 5′‐ O ‐phosphates.",10.1002/ejoc.201200819,2012-07-26,0.5897972621449076
Organic Letters,Synthesis of the C16−C28 Spiroketal Subunit of Spongistatin 1 (Altohyrtin A):  The Pyrone Approach,The synthesis of the CD spiroketal fragment of spongistatin 1 (altohyrtin A) has been accomplished utilizing the addition of a metalated pyrone to an aldehyde and subsequent acid-catalyzed spirocyclization. A stereoselective hydrogenation and subsequent conformational inversion establish the C19 stereocenter and the axial-equatorial spiroketal center.,10.1021/ol005605e,2000-03-07,0.5897951294281527
Tetrahedron,A new approach to the total synthesis of steroids,,10.1016/s0040-4039(01)88490-2,1969-01-01,0.5897935316261789
Tetrahedron,A new approach to the total synthesis of B-norsteroids,,10.1016/s0040-4039(01)87844-8,1969-01-01,0.5897935316261789
Tetrahedron,A new approach to corticoid total synthesis,,10.1016/s0040-4039(01)96766-8,1971-01-01,0.5897935316261789
Angewandte Chemie International Edition,Enantioselective Total Synthesis of Amphidinolide F,"A common-intermediate approach is utilized in the total synthesis of amphidinolide F (see scheme, left) to access both the C1–C8 and the C18–C25 portions of the macrolide. A silver-catalyzed rearrangement/cyclization was employed to construct the two tetrahydrofuran rings. A Felkin-controlled, dienyl lithium addition to an α-chiral aldehyde incorporated both the C9–C11 diene and the alcohol at C8. An umpolung sulfone alkylation/oxidative desulfurization sequence is employed to couple the two moieties.",10.1002/anie.201203935,2012-07-05,0.589792201871537
Organic Process Research & Development,"Development of a Manufacturing Process for a Key <i>(S)</i>-5-(2,2-Dimethyltetrahydro-2<i>H</i>-pyran-4-yl)-1<i>H</i>-indole Intermediate for Orforglipron. Part II. Development of a CSTR Process for Evans Auxiliary-Assisted Asymmetric 1,4-Addition","A scalable 8-step route incorporating Evans auxiliary-assisted asymmetric 1,4-addition was developed for a key (S) -5-(2,2-dimethyltetrahydro-2 H -pyran-4-yl)-1 H -indole intermediate of orforglipron. The main challenges of the batch process included the copper complex’s stability, the high exothermicity of the reaction, and the control of a key diastereomeric impurity. These challenges were addressed by developing a CSTR process to prepare the copper complex, enabling “on-demand” preparation and improved heat transfer to control the reaction temperature. A simple slurry purification was devised to isolate a metastable polymorph that effectively reduced the diastereomeric impurity to acceptable levels. The optimized process was successfully scaled up to >400 kg, demonstrating its robustness.",10.1021/acs.oprd.5c00184,2025-08-04,0.58979174013261
Journal of the American Chemical Society,Biomimetic Synthesis of Antimalarial Naphthoquinones,"The total synthesis of naphthoquinone natural products isolated from the Bignoniaceae plant\nfamily is described. Pinnatal, isopinnatal, sterekunthals A and B, pyranokunthones A and B, and\nanthrakunthone have been prepared along the lines of a biosynthetic proposal involving pericyclic reactions\nas key steps. The first case of catalysis in oxa 6π electrocyclizations is reported.",10.1021/ja069018l,2007-01-23,0.5897890758543127
Green Chemistry,Towards a greener synthesis of (S)-3-aminobutanoic acid: process development and environmental assessment,"An improved, greener process for the enantioselective chemoenzymatic synthesis of (S)-3-aminobutanoic acid has been developed. Reaction steps comprise an initial aza-Michael addition starting from cheap prochiral compounds, subsequent enzymatic resolution via aminolysis using commercially available Candida antarctica lipase B in a solvent-free one-pot process, hydrolysis of the resulting ester and removal of the N-benzyl moiety via hydrogenation. After isolation, the desired (S)-3-aminobutanoic acid was obtained in an overall yield of 28% and with an excellent enantiomeric excess of 99% ee. Notably, this reaction sequence does not require column chromatography with organic solvents and only one purification step of an intermediate is needed. The environmental impact of this optimized process has been evaluated and an E-factor of 41 has been calculated for the overall process. A comparative assessment with the previous process was done via mass balancing using the E-factor, the selectivity index S−1 as well as an SHE assessment.",10.1039/c002721a,2010-01-01,0.5897883560058985
Journal of Organic Chemistry,Synthesis of C13−C25 Fragment of 24-Demethylbafilomycin C<sub>1</sub> via Diastereoselective Aldol Reactions of a Ketone Boron Enolate as the Key Step,"An efficient synthesis of the C13-C25 fragment is described for 24-demethylbafilomycin C1, a new member of the plecomacrolide family isolated from fermentation broth of Streptomyces sp. CS which is a commensal microbe of Maytenus hookeri. The targeted C13-C25 fragment possesses five oxygenated and three methyl-substituted stereogenic centers. It is obtained through formation of the C17-C18 syn aldol by using an ethyl ketone boron enolate with diastereomeric ratios of 95:5 and 83:17, respectively, for the chiral aldehydes substituted with acetoxy and methoxyacetoxy groups at C15. The results confirm the observation that the stereochemistry at C22 of the ketone is determinant to the diastereoselectivity of the aldol reaction. The synthesized C13-C25 fragment having a methoxyacetoxy group at C15 is considered as a useful precursor for construction of the 16-membered ring lactone of 24-demethylbafilomycin C1 through an aldol condensation of the methoxyacetate followed by formation of the C12-C13 double bond via a diene-ene RCM reaction.",10.1021/jo070624o,2007-05-23,0.5897728540952015
Tetrahedron,Asymmetric heck reaction. A catalytic asymmetric synthesis of the key intermediate for vernolepin,,10.1016/s0040-4039(00)60532-4,1993-06-01,0.5897670864504605
Tetrahedron,Selective reductive cleavage of 2-(phenylthio)pyrimidines for efficient synthesis of 2-(H)pyrimidines,,10.1016/j.tetlet.2019.07.002,2019-07-04,0.5897627294248899
Journal of the American Chemical Society,"Synthetic Enantiopure Aziridinomitosenes:  Preparation, Reactivity, and DNA Alkylation Studies","An enantiocontrolled route to aziridinomitosenes had been developed from l-serine methyl ester hydrochloride. The tetracyclic target ring system was assembled by an internal azomethine ylide cycloaddition reaction based on silver ion-assisted intramolecular oxazole alkylation and cyanide-induced ylide generation via a labile oxazoline intermediate (62 to 66). Other key steps include reductive detritylation of 26, methylation of the N-H aziridine 56, oxidation of the sensitive cyclohexenedione 68 to quinone 70, and carbamoylation using Fmoc-NCO. Although the aziridinomitosene tetracycle is sensitive, a range of protecting group manipulations and redox chemistry can be performed if suitable precautions are taken. A study of DNA alkylation by the first C-6,C-7-unsubstituted aziridinomitosene 11a has been carried out, and evidence for DNA cross-link formation involving nucleophilic addition to the quinone subunit is described.",10.1021/ja030452m,2003-12-01,0.589756876463865
Journal of Organic Chemistry,New Concise Total Synthesis of (+)-Lentiginosine and Some Structural Analogues,"An efficient and concise total synthesis of (+)-lentiginosine (1) starting from an L-tartaric acid-derived nitrone using organometallic addition, indium-catalyzed reduction, and ring-closing metathesis reaction as the key steps is reported. Structural analogues of (+)-1 have been also synthesized, and their inhibitory activity toward 22 commercially available glycosidases has been evaluated.",10.1021/jo0509408,2005-07-14,0.5897414347882485
European Journal of Organic Chemistry,Collective Total Synthesis of 4‐Azafluorenone Alkaloids,"Abstract 4‐Azafluorenones are typically obtained by acid‐mediated cyclization of 2‐arylnicotinates. However, this approach fails to give 5‐oxygenated 4‐azafluorenones due to lactonization of 2‐(2‐alkoxy)phenylnicotinate intermediates. Herein, we report two modifications of established approaches to 4‐azafluorenone synthesis that, either in combination or by themselves, enable the flexible preparation of 4‐azafluorenones with diverse oxygenation patterns in the benzenoid ring. Undesired lactonization was circumvented via tert ‐butyl hydroperoxide (TBHP)‐mediated radical cyclization of 2‐aryl‐3‐(hydroxymethyl)pyridines. In the absence of suitable protecting groups for phenolic intermediates, bromide substituents were regioselectively introduced as latent hydroxy groups and later converted under palladium catalysis. We present the first total syntheses of five 4‐azafluorenone alkaloids muniranine, darienine, 5,8‐dimethoxy‐7‐hydroxyonychine, 5,6,7,8‐tetramethoxyonychine, and 6,8‐dihydroxy‐7‐methoxyonychine in addition to new total syntheses of six 4‐azafluorenone alkaloids and one related pyridocoumarin alkaloid.",10.1002/ejoc.202300399,2023-06-07,0.5897394555595211
Tetrahedron,Transmonocyanoacetylation of phenylenediamines: a simple and efficient synthesis of novel N-(aminophenyl)-2-cyanoacetamides and their derivatives,,10.1016/j.tetlet.2015.11.098,2015-11-30,0.5897344986929238
Organic Letters,A Catalytic Homo-Nazarov Cyclization Protocol for the Synthesis of Heteroaromatic Ring-Fused Cyclohexanones,"A general protocol for the catalytic homo-Nazarov cyclization of cyclopropyl heteroaryl ketones has been developed, which employs indium triflate as the promoter. A range of heteroaromatic ring-fused cyclohexanones was synthesized in 56-91% yield using this protocol. An example of a tandem cyclopropanation/homo-Nazarov cyclization is also reported in which the one-pot yield is greater than the overall yield of the two individual steps.",10.1021/ol200305n,2011-03-18,0.5897320819339308
Organic Letters,Diastereoselective Synthesis of Cyclopentapyridazinones via Radical Cyclization: Synthetic Studies Toward Halichlorine,The pyridazinone ring system serves as an excellent scaffold for the diastereoselective preparation of novel cis-fused cyclopentapyridazinones utilizing the directed 5-exo radical cyclization approach. This overall approach was successfully employed in the preparation of a functionalized aza-spirocycle.,10.1021/ol801849u,2008-09-25,0.5897182403605933
Tetrahedron,Approaches towards the total synthesis of carolacton: synthesis of C1–C16 fragment,,10.1016/j.tetlet.2015.03.002,2015-03-05,0.5897105222063639
Tetrahedron,Synthesis of the FGH ring fragment of ciguatoxin,,10.1016/s0040-4039(98)02606-9,1999-02-01,0.5897001774345294
Tetrahedron,Synthesis of the LMN-ring fragment of the Caribbean ciguatoxin C-CTX-1,,10.1016/j.tetlet.2007.01.103,2007-01-25,0.5897001774345294
European Journal of Organic Chemistry,A Simple Enantioselective Route to Functionalized Indolizidines: Synthesis of (+)‐Ipalbidine and (+)‐Antofine,"Abstract An efficient route to functionalized indolizidines from an enantiomerically enriched γ‐nitro ketone is described. The nitro ketone is obtained by an organocatalytic, enantioselective ketone‐nitro alkene Michael addition. Oxidative ring expansion of the nitro ketone and subsequent methanolysis provides a 8‐nitro‐4‐oxooctanoate. This is stereoselectively transformed to the key, functionalized indolizidine intermediate which is readily converted to (+)‐ipalbidine and (+)‐antofine.",10.1002/ejoc.201100125,2011-02-18,0.5896976027605507
Tetrahedron,Copper-catalyzed chalcogenoamination of 2-alkynylanilines with dichalcogenides for one-step synthesis of 3-sulfenylindoles and 3-selenylindoles,,10.1016/j.tetlet.2011.01.052,2011-01-24,0.589695537314207
Synlett,"An Efficient One-Pot Multicomponent Synthesis of Tetracyclic Quinazolino[4,3-b]quinazolines by Sequential C–N Bond Formation and Copper-Mediated Aerobic Oxidative Cyclization","An efficient one-pot synthesis of quinazolino[4,3-b]quinazoline derivatives has been accomplished, starting from 2-(2-bromo­phenyl)quinazolin-4(3H)-one, aldehydes, and various nitrogen sources under aerobic conditions. The multicomponent protocol is mediated by copper(I) salts and involves amination of 2-(2-bromophenyl)quinazolin-4(3H)-one, followed by condensation with the aldehyde and an oxidative cyclization to give the target compounds in moderate to good yields.",10.1055/s-0036-1591578,2018-05-04,0.5896945087357243
Synlett,Convergent Synthesis of 1 → 3 C-Branched Polyamide Dendrons,All articles of this category A convergent synthesis of 1 → 3 C -branched polyamide dendrons was developed providing a facile access to defined monodisperse dendritic building blocks. dendritic building block - convergent synthesis,10.1055/s-1998-1945,1998-12-01,0.5896922420674918
Synthesis,Synthesis of New Aryloxyacetic Acid Derivatives,,10.1055/s-1983-30429,1983-01-01,0.5896892523776819
Tetrahedron,Synthesis of new dendrimers—trimesic acid derivatives,,10.1016/j.tetlet.2010.11.016,2010-11-12,0.5896892523776819
Journal of Organic Chemistry,Highly diastereoselective alkylation of chiral tin(II) enolates onto cyclic acyl imines. An efficient asymmetric synthesis of bicyclic alkaloids bearing a nitrogen atom ring juncture,"Asymmetric alkylation onto 5-acetoxy-2-pyrrolidinone (5, n = 1) in THF employing chiral tin(II) enolates 4a,b,e,f obtained from treatment of the corresponding 3-acyl-4(S)- or -4(R)-isopropyl-l,3-thiazolidine-2-thiones 3a,b,e,f with Sn(OSO<sub>2</sub>CF<sub>3</sub>)<sub>2</sub>and N-ethylpiperidine in THF afforded the corresponding C (5)-alkylated 2-pyrrolidinones 6, 7,12, and 13 in 67-92% yields and in a highly diastereoselective manner [91-97% diastereomer excess (de)]. Similar alkylation of 4e onto 6-acetoxy-2-piperidinone (5, n = 2) gave the C (6)-alkylated 2-piperidinone 14 in 63% yield and in 96% de. Complete enolization of 3c,d,g was achieved by employing 2 mol equiv of Sn(OSO<sub>2</sub>CF<sub>3</sub>)<sub>2</sub>and 2.2 mol equiv of N-ethylpiperidine at -5 to 0 °C in THF. Subsequently, diastereoselective alkylation onto cyclic acyl imines derived from 5 (n = 1 and 2) in situ using the tin(II) enolates 4c,d,g gave the chiral alkylated lactams 8–11 and 15 in 57-73% yields and in 91-98% de. A six-membered chelated transition state (e.g., 16) is proposed for the highly diastereoselective alkylation with various chiral tin(II) enolates onto 5 (n = 1 and 2). Simplified reductive annulation of 8–11 and 15 with LiAlH4proceeded smoothly to furnish optically pure (-)-trachelanthamidine (17a), two kinds of indolizidine type compounds 17b,c, (-)-epilupinine (17d), and (+)-epilupinine (21) together with the corresponding hydrogenolysis products 19a-d and 23, respectively. Chiral lactam 6 was readily converted to carboxylic acid 26, the synthetic precursor of (S)-homoproline 27, and the chiral diester 31, which could be exploited for the asymmetric synthesis of various chiral pyrrolizidine alkaloids via 32.",10.1021/jo00291a012,1990-02-01,0.5896878002986898
Journal of Organic Chemistry,"A Three-Step Method for the Preparation of <i>N</i>-Substituted 3,4-Dihydroisoquinolin-1(2<i>H</i>)-ones and Heteroaryl-Fused 3,4-Dihydropyridin-2(1<i>H</i>)-ones from 2-Bromobenzoate Precursors","We demonstrate a general method for the preparation of diverse N -substituted 3,4-dihydroisoquinolin-1(2 H )-one compounds through an overall three-step cross-coupling/cyclization/ N -deprotection/ N -alkylation sequence. In the first step, ethyl 2-bromobenzoates and 2-bromo-1-carboxyethyl heterocycles are cross-coupled with commercially available potassium (2-(( tert -butoxycarbonyl)amino)ethyl)trifluoroborate to produce (hetero)aryl-substituted 3-[( N -Boc-2-carboxyethyl)phenyl]ethylamines. In a subsequent two-stage process, these (hetero)arylethylamines undergo base-mediated ring closure followed by N -deprotection and N -alkylation to produce N -substituted 3,4-dihydroisoquinolin-1(2 H )-ones and heteroaryl-fused N -benzyl 3,4-dihydropyridin-2(1 H )-ones. Mechanistic work was performed to elucidate the order of transformations for the latter two-stage process. The method was also extended to the production of N -benzyl isoindolin-1-one and N -benzyl 2,3,4,5-tetrahydro-1 H -benzo[ c ]azepin-1-one.",10.1021/acs.joc.2c02670,2023-01-27,0.5896827757116672
Angewandte Chemie International Edition,Synthesis of the Monomeric Unit of the Lomaiviticin Aglycon,"The right building blocks: The monomeric unit of the lomaiviticin aglycon (see structures) was synthesized through an enantioselective route featuring an Ullmann coupling, a benzoin-type cyclization, and a novel SmI2-mediated allylic alcohol formal transposition.",10.1002/anie.200902509,2009-07-02,0.5896825379671109
Journal of Organic Chemistry,"A New Facile Approach to the Synthesis of 3-Methylthio-Substituted Furans, Pyrroles, Thiophenes, and Related Derivatives","2-(methylthio)-1,4-diaryl-2-butene-1,4-dione (3) are prepared from readily available aryl methyl ketones in the presence of copper(II) oxide, iodine, and dimethyl sulfoxide. The success of the cross-coupling reaction of 4-chloroacetophenone with 2-acetylthiophene confirms a proposed self-sorting tandem reaction mechanism. Both Z- and E-isomers of compound 3 are readily converted into the corresponding 3-methylthio 2,5-diaryl furan 7 in good yield through a domino process involving the reduction of the double bond followed by the Paal-Knorr furan synthesis. Meanwhile, 4-bromo-3-methylthio 2,5-diaryl furan 10 is obtained either by the treatment of furan 7 with molecular bromine or by the treatment of diketone 3 with 30% hydrogen bromide in acetic acid solution in one pot. Removal of the methylthio group is accomplished by the treatment of 7 with Raney Ni in ethanol, which affords the diaryl-substituted furan 11 in excellent isolated yield. Selective reduction of the double bond of compound 3 leads to the formation of the saturated 1,4-diketone 13, which is easily converted to the corresponding 3-methylthio-2,5-diaryl-substituted pyrrole 14 and thiophene 15 via the Paal-Knorr cyclization reaction.",10.1021/jo702585s,2008-03-20,0.5896795420264955
Journal of Organic Chemistry,Asymmetric Library Synthesis of P-Chiral <i>t</i>-Butyl-Substituted Secondary and Tertiary Phosphine Oxides,"An asymmetric synthesis, amenable to library preparation of structurally diverse P -chiral t -butyl substituted secondary phosphine oxides (SPOs) and tertiary phosphine oxides (TPOs), was developed. A P -chiral H-phosphinate building block was prepared via a two-step, one-pot condensation of a chiral auxiliary with t -BuPCl 2, followed by hydrolysis. Nucleophilic displacement of the chiral auxiliary with Grignard reagents, followed by hydrolysis, provided a library of P -chiral SPOs. In situ treatment of the prehydrolysis intermediate with electrophiles also provided a library of P -chiral TPOs in high enantiomeric purity.",10.1021/acs.joc.9b00945,2019-05-17,0.5896791514504944
Tetrahedron,"A novel traceless route to synthesize 3,5-disubstituted-1,2,4-triazoles on PEG6000",,10.1016/j.tetlet.2005.10.011,2005-10-24,0.5896775670167558
Tetrahedron,A new method for the synthesis of amides from imines,,10.1016/j.tetlet.2011.11.018,2011-11-10,0.5896771850005891
Tetrahedron,A new method for the synthesis of dichlorophosphines,,10.1016/j.tetlet.2010.12.048,2010-12-18,0.5896771850005891
Tetrahedron,A new method for the synthesis of Δ1-butenolides,,10.1016/s0040-4039(01)99685-6,1966-01-01,0.5896771850005891
Tetrahedron,A new method for the synthesis of pyrazolidines,,10.1016/j.tetlet.2016.05.011,2016-05-14,0.5896771850005891
Tetrahedron,"New method for synthesis of acylalkylidene-2,3-dihydrofurans /2-furylideneacetophenones/",,10.1016/s0040-4039(01)93003-5,1977-01-01,0.5896771850005891
Tetrahedron,A new method for the synthesis of butatrienes,,10.1016/s0040-4039(01)97578-1,1971-01-01,0.5896771850005891
Tetrahedron,Synthesis of tigogenyl β-O-cellobioside heptaacetate and glycoside tetraacetate via Schmidt's trichloroacetimidate method; some new observatons.,,10.1016/s0040-4039(00)97637-8,1990-01-01,0.5896771850005891
Tetrahedron,New method of polyhaloadamantane synthesis,,10.1016/s0040-4039(01)94000-6,1972-01-01,0.5896771850005891
Tetrahedron,A new method for the synthesis of the marine alkaloid fascaplysin,,10.1016/j.tetlet.2010.09.120,2010-10-09,0.5896771850005891
Tetrahedron,"New method of synthesis of 1,1′-dialkyl-2,2′-dibenzimidazoliles",,10.1016/s0040-4039(01)99155-5,1968-01-01,0.5896771850005891
Tetrahedron,A new method for the synthesis of glycosyl fluorides,,10.1016/s0040-4039(00)98450-8,1985-01-01,0.5896771850005891
Tetrahedron,"A new method for the synthesis of 2,6-dinitro and 2-halo-6-nitrostyrenes",,10.1016/s0040-4039(00)01101-1,2000-08-01,0.5896771850005891
Tetrahedron,A new method for the synthesis of dinucleotides,,10.1016/s0040-4039(01)84975-3,1972-01-01,0.5896771850005891
Tetrahedron,A new method for the synthesis of plurisubstituted pyrroles,,10.1016/j.tetlet.2003.09.099,2003-10-16,0.5896771850005891
Tetrahedron,A new method for the synthesis of branched ribonucleotides,,10.1016/s0040-4039(00)95416-9,1987-01-01,0.5896771850005891
Synthesis,A New Method for the Synthesis of Pyridines,,10.1055/s-1975-23710,1975-01-01,0.5896771850005891
Tetrahedron,A new method for the synthesis of n-arylphthalisoimides,,10.1016/s0040-4039(00)78804-6,1991-06-01,0.5896771850005891
Angewandte Chemie International Edition,Regioselective and Enantioselective Synthesis of β‐Indolyl Cyclopentenamides by Chiral Anion Catalysis,"The regioselective and enantioselective synthesis of β-indolyl cyclopentenamides, a versatile chiral building block, by asymmetric addition of indoles to α,β-unsaturated iminium intermediates has been achieved through chiral anion catalysis. Key to the success of this methodology is the generation of a chiral anion-paired ketone-type α,β-unsaturated iminium intermediate from α-hydroxy enamides. Preliminary mechanistic studies and DFT calculations are consistent with a mechanism involving multiple, concurrent pathways for isomerization of the initially formed azaallylcation into the key α,β-unsaturated iminium intermediate, all mediated by the phosphoric acid catalyst.",10.1002/anie.201807010,2018-08-22,0.5896764066112106
Tetrahedron,A highly convergent approach for the synthesis of disaccharide repeating units of peptidoglycan,,10.1016/s0040-4039(02)01753-7,2002-10-01,0.5896731245211793
Synthesis,"A Stereoselective Route to cis-(2S,3R)-3-Hydroxypipecolic Acid and Two Enantiomeric cis-2-Hydroxymethyl-3-hydroxypiperidine Derivatives","Stereoselective routes to cis-(2S,3R)-3-hydroxypipecolic acid and two enantiomeric cis-2-hydroxymethyl-3-hydroxypiperidine derivatives from a common precursor have been developed, which featured stereocontrolled vinylation of a α-chiral aldehyde and ring-closing metathesis as key steps.",10.1055/s-0030-1260120,2011-07-14,0.5896729322314053
Journal of Organic Chemistry,Synthesis of Racemic Brevioxime and Related Model Compounds,"The synthesis, in racemic form, of the insect juvenile hormone inhibitor brevioxime (1) is described, as well as exploratory studies that led to the related model compounds 14 and 15a. The route to 1 involves Ag(+)-mediated coupling of the amine derived from 20 with the beta-keto thioester 32. Acid treatment of the coupled product 33 led by acetal hydrolysis, cyclization, and desilylation to 34a,b, from which 1 was reached by oxidation and conversion into the oxime. In the synthesis of the amino component 20, a known, but unusual, reduction was used for converting a nitrile into an amine hydrochloride.",10.1021/jo0003551,2000-07-08,0.5896704610862271
Synlett,An Efficient Approach to the Synthesis of a Key Precursor of Mammalian Squalene Epoxidase Inhibitors Using a New Method for Transforming Aryl Bromides to Phenols,"All articles of this category Phenol 4 , a key precursor of mammalian squalene epoxidase inhibitors, is obtained through a straightforward three steps synthesis using a new aryl bromide to phenol transformation. Squalene epoxidase - inhibitor - oxidation - aryl boronate - phenol",10.1055/s-1995-5117,1995-09-01,0.5896655225850662
Tetrahedron,"2-(o-Tolyl)-4, 4-dimethyl-2-oxazolines — A new vehicle for facile convergent synthesis of protoberberine alkaloids",,10.1016/s0040-4039(98)00744-8,1998-06-01,0.5896625949602591
Tetrahedron,"Efficient total synthesis of 5-oxo-6(E),8(Z),11(Z),14(Z)-eicosatetraenoic acid (5-oxo-ETE), a potent proinflammatory autacoid",,10.1016/s0040-4039(01)00668-2,2001-06-01,0.5896560949092616
Organic Letters,Total Synthesis of (−)-Pironetin,"[structure: see text] The asymmetric total synthesis of pironetin, a compound that shows plant growth regulatory activity, immunosuppressive as well as a remarkable antitumoral activity, is described. The approach involves the use of three very efficient Evans oxazolidinone-mediated syn-aldol condensations, a high-yielding coupling between lithium acetylide ethylenediamine complex and a tosylate followed by methylation, and selective reduction to establish the C12-C13 (E) double bond.",10.1021/ol027211o,2003-01-09,0.5896470424362533
Tetrahedron,Vinylsilane-mediated polyene cyclization. Synthesis of the octahydronaphthalenol portion of dihydrocompactin.,,10.1016/s0040-4039(00)98414-4,1985-01-01,0.5896469429485514
Angewandte Chemie International Edition,Total Synthesis of (−)‐Sarain A,"The final synthetic challenges associated with sarain A have been overcome, thus leading to its first total synthesis. Critical to success was a late-stage intramolecular Stille coupling to construct the unsaturated macrocyclic ring and introduce the skipped triene functionality of the natural product.",10.1002/anie.200600417,2006-03-27,0.5896438058476179
Organic Letters,Concise Synthesis of the C15–C38 Fragment of Okadaic Acid: Application of the Suzuki–Miyaura Reaction to Spiroacetal Synthesis,"A concise synthetic entry to the C15-C38 fragment of okadaic acid by exploiting a Suzuki-Miyaura reaction for the rapid assembly of the spiroacetal substructures has been developed. The present synthesis was completed in 19 linear steps from a commercially available material, showcasing the efficiency of our synthetic strategy.",10.1021/ol503491t,2014-12-26,0.589643465024049
Synlett,"Asymmetric Synthesis of 1,3-Dialkyl-Substituted Carbon Chains of any Stereochemical Configuration by an Iterable Process","All articles of this category A highly practical, iterable method for the preparation of 1,3,5,n(odd)-polyalkyl-substituted carbon chains based upon the asymmetric alkylation of pseudoephedrine amide enolates is described. asymmetric synthesis - pseudoephedrine - enolate - alkylation",10.1055/s-1997-6121,1997-06-01,0.589642943556719
Tetrahedron,Chiral synthetic macrodiolide and macrotriolide ionophores with C2- and C2symmetry,,10.1016/s0040-4039(00)98051-1,1990-01-01,0.5896381021839951
European Journal of Organic Chemistry,Total Synthesis of (R)- and (S)-semi-Vioxanthin,"Compounds (R)- and (S)-semi-vioxanthin 2 were synthesized by a tandem Michael reaction of orsellinate 3 and the chiral Michael acceptors 4. The key step for the formation of lactone (R)-4 is a regio- and enantioselective, enzyme-catalyzed reduction of tert-butyl 3,5-dioxohexanoate (5) by an alcoholdehydrogenase from Lactobacillus brevis. Compound (S)-4 was synthesized by the Claisen condensation of tert-butyl acetate and ethyl (S)-3-hydroxy-butanoate (8). Cleavage of the benzyloxymethyl groups in the protected (R)- and (S)-semi-vioxanthins was achieved by hydrogenolysis to afford (R)-2 and (S)-2, respectively.",10.1002/1099-0690(200101)2001:1<211::aid-ejoc211>3.0.co;2-r,2001-01-01,0.5896305955670971
European Journal of Organic Chemistry,Total Synthesis of (R)- and (S)-semi-Vioxanthin,"Compounds (R)- and (S)-semi-vioxanthin 2 were synthesized by a tandem Michael reaction of orsellinate 3 and the chiral Michael acceptors 4. The key step for the formation of lactone (R)-4 is a regio- and enantioselective, enzyme-catalyzed reduction of tert-butyl 3,5-dioxohexanoate (5) by an alcoholdehydrogenase from Lactobacillus brevis. Compound (S)-4 was synthesized by the Claisen condensation of tert-butyl acetate and ethyl (S)-3-hydroxy-butanoate (8). Cleavage of the benzyloxymethyl groups in the protected (R)- and (S)-semi-vioxanthins was achieved by hydrogenolysis to afford (R)-2 and (S)-2, respectively.",10.1002/1099-0690(200101)2001:1<211::aid-ejoc211>3.3.co;2-i,2001-01-01,0.5896305955670971
Tetrahedron,Electroreductive intermolecular coupling of ketones with O-methyl oximes. A convenient route to synthesis of 2-amino alcohols,,10.1016/s0040-4039(00)79486-x,1991-01-01,0.5896279019074091
Organic Process Research & Development,"Scale-Up of Trisodium [(3β,5β,12α)-3-[[4(<i>S</i>)-4-[Bis[2-[bis[(carboxy-<i>kO</i>)methyl]amino-<i>kN</i>]ethyl]amino-<i>kN</i>]-4-(carboxy-<i>kO</i>)-1-oxobutyl]amino]-12-hydroxycholan-24-oato(6-)]gadolinate(3-)], a Gd(III) Complex under Development As a Contrast Agent for MRI Coronary Angiography","Process chemistry involved in the discovery and development routes to trisodium [(3β,5β,12α)-3-[[4( S )-4-[bis[2-[bis[(carboxy- kO )methyl]amino- kN ]ethyl]amino- kN ]-4-(carboxy- kO )-1-oxobutyl]amino]-12-hydroxycholan-24-oato(6-)]gadolinate(3-)] ( B22956/1 ) starting from l -glutamic acid and (3α,5β,12α)-3,12-dihydroxycholan-24-oic acid is described. The best process is based on seven chemical steps and overcomes difficult purification protocols. Such process has been successfully implemented to prepare multikilogram batches of the target compound in 20% overall yield from (3α,5β,12α)-3,12-dihydroxycholan-24-oic acid.",10.1021/op900008a,2009-05-22,0.5896270026719721
Journal of Organic Chemistry,"Convenient Syntheses of 3′-Amino-2′,3′-dideoxynucleosides, Their 5′-Monophosphates, and 3′-Aminoterminal Oligodeoxynucleotide Primers","5'-Protected 3'-amino-2',3'-dideoxynucleosides containing any of the four canonical nucleobases (A/C/G/T) were prepared via azides in five to six steps, starting from deoxynucleosides. For pyrimidines, the synthetic route involved nucleophilic opening of anhydronucleosides. For purines, an in situ oxidation/reduction sequence, followed by a Mitsunobu reaction with diphenyl-2-pyridylphosphine and sodium azide, provided the 3'-azidonucleosides in high yield and purity. For solid-phase synthesis of aminoterminal oligonucleotides, aminonucleosides were linked to controlled pore glass through a novel hexafluoroglutaric acid linker. These supports gave 3'-aminoterminal primers in high yield and purity via conventional DNA chain assembly and one-step deprotection/release with aqueous ammonia. Primers thus prepared were successfully tested in enzyme-free chemical primer extension, an inexpensive methodology for genotyping and labeling. Protected 5'-monophosphates of 3'-amino-2',3'-dideoxynucleosides were also prepared, providing starting materials for the preparation of labeled or photolably protected monomers for chemical primer extension.",10.1021/jo8018889,2008-11-16,0.5896229648365303
Organic Letters,A New Route to <i>C</i>-Aryl Glycosides,[reaction: see text] A six-step route for de novo synthesis of C-aryl glycosides based on cycloaddition of an aryl nitrile oxide with 4-pentyn-2-ol has been developed.,10.1021/ol025549c,2002-02-16,0.5896203020212462
Synlett,Synthetic Study on Stemona Alkaloids. Highly Stereoselective Construction of α-Methyl-γ-lactone Substituted 1-Azabicyclo[5.3.0]decanes,"All articles of this category Tricyclic ring system 6 , common central structure present in most Stemona alkaloids, was stereoselectively constructed through TMSOTf catalyzed condensation reaction of α- t -butyldioxypyrrolidine 13 with 3-methyl-2-trimethylsilyloxyfuran and subsequent azepane ring formation via intramolecular N -alkylation of iodide 17 . Stemona Alkaloid - 1-Azabicyclo[5.3.0]decane - α-Methyl-γ-lactone - threo -Selective - 3-Methyl-2-trimethylsilyloxyfuran",10.1055/s-1995-5255,1995-12-01,0.5896154884505949
Organic Process Research & Development,"Efficient Synthesis of 1,4-Diaryl-5-methyl-1,2,3-triazole, A Potential mGluR1 Antagonist, and the Risk Assessment Study of Arylazides","A concise and practical synthesis of a 1,4-diaryl-5-methyl-1,2,3-triazole is described. A mGluR1 antagonist 1 was prepared with one-pot operation by the Negishi coupling reaction between two building blocks, 5-bromophthalimidine ( 2 ) and 1-aryl-5-methyl-4-triazolylzinc ( 3- Zn ). Bromide 2 was synthesized via N -selective cyclization of o -hydroxymethylbenzamide 8 easily prepared from phthalide 4 . Zinc species 3- Zn was generated in situ by transmetalation of 1-aryl-4-magnesio-5-methyltriazole ( 3- Mg ), which in turn was generated by the regioselective click chemistry between 2,4-difluorophenylazide ( 5 ) and propynylmagnesium bromide. The risk assessment of potentially explosive arylazides is also mentioned.",10.1021/op900062p,2009-05-12,0.5896044382115789
Organic Letters,Total Synthesis of (+)-Tubelactomicin A. 2. Synthesis of the Upper-Half Segment and Completion of the Total Synthesis,"[reaction: see text]. We have completed the total synthesis of natural (+)-tubelactomicin A (1), a 16-membered macrolide antibiotic. This Letter presents a highly efficient synthesis of the upper-half segment (C14-C24) and the completion of the total synthesis featuring a high-yielding Stille coupling for the connection of the upper-half and lower-half segments and Mukaiyama macrolactonization for the construction of the entire structure of 1.",10.1021/ol050763x,2005-04-29,0.589602118007913
European Journal of Organic Chemistry,Synthesis of Angucycline/Tetrangulol Derivatives Using Suzuki‐Miyaura Cross‐Coupling and Ring‐Closing Carbonyl‐Olefin Metathesis Reactions,"Abstract Key steps in the synthesis of derivatives of the angucycline, tetrangulol include the use of a palladium catalyzed Suzuki‐Miyaura cross‐coupling reaction for the assembly of 2‐(1,4‐dimethoxy‐3‐(2‐methylprop‐1‐en‐1‐yl)naphthalen‐2‐yl)‐3‐methoxy‐5‐methylbenzaldehyde from 2‐iodo‐3‐methoxy‐5‐methylbenzaldehyde and 2‐(1,4‐dimethoxy‐3‐(2‐methylprop‐1‐en‐1‐yl)naphthalen‐2‐yl)‐4,4,5,5‐tetramethyl‐1,3,2‐dioxaborolane. The biaryl product was then subjected to an iron‐catalyzed ring‐closing carbonyl‐olefin metathesis reaction to afford 1,7,12‐trimethoxy‐3‐methyltetraphene, which was oxidized to the corresponding quinone. Late stage oxidation of the quinone with Ru[Cl 2 ( p ‐cymene)] 2 and an oxidant unexpectedly afforded the chlorinated compounds, 2,4‐dichloro‐11‐hydroxy‐1‐methoxy‐3‐methyltetraphene‐7,12‐dione and 2,4‐dichloro‐6‐hydroxy‐1‐methoxy‐3‐methyltetraphene‐7,12‐dione.",10.1002/ejoc.202200348,2022-05-16,0.5895965468644718
Organic Letters,New Route to Azaspirocycles via the Organolithium-Mediated Conversion of β-Alkoxy Aziridines into Cyclopentenyl Amines,"A new three-step route to azaspirocycles involving the organolithium-mediated conversion of beta-alkoxy aziridines into substituted cyclopentenyl amines, hydroboration, and cyclization has been developed. The methodology is utilized in the construction of the pentacyclic ring system of cephalotaxine. [reaction: see text]",10.1021/ol062073e,2006-10-01,0.5895917036829701
Tetrahedron,"Two-step synthesis of -elaeocarpine, utility of dihydropyridines as a versatile synthetic intermediate",,10.1016/s0040-4039(01)97451-9,1971-01-01,0.5895820195129583
Synthesis,Synthesis of the C1-C14 Fragment of Sarcoglaucol-16-one via Z-Selective Ando-Type Horner-Wadsworth-Emmons Olefination,"A synthetic strategy involving a Z-selective Horner-Wadsworth-Emmons olefination was developed for the preparation of the sarcoglaucolone precursor methyl (2Z,6E)-8-(methoxymeth­oxy)-6-methyl-2-[(3E)-4-methyl-5-oxopent-3-enyl]-9-[(trimethylsilyl)methyl]deca-2,6,9-trienoate. The target compound was isolated in a E/Z ratio of 17:83",10.1055/s-0029-1218825,2010-06-18,0.5895750768005502
Tetrahedron,"A novel atom-efficient, one-pot synthesis of sulfonylguanidines and sulfamoylguanidines",,10.1016/j.tetlet.2011.04.031,2011-04-21,0.5895749297646687
Journal of the American Chemical Society,Catalytic Enantioselective Synthesis of Morpholinones Enabled by Aza-Benzilic Ester Rearrangement,"Chiral morpholinone is an important building block in organic synthesis and a pharmacophore in medicinal chemistry. However, catalytic enantioselective methods for the construction of this N, O -heterocycle remain scarce. We report herein a chiral phosphoric acid-catalyzed enantioselective synthesis of C3-substituted morpholinones from aryl/alkylglyoxals and 2-(arylamino)ethan-1-ols. The reaction proceeds through a domino [4 + 2] heteroannulation followed by a 1,2-aryl/alkyl shift of the resulting cyclic α-iminium hemiacetals. It represents formally an unprecedented asymmetric aza-benzilic ester rearrangement reaction. A concise synthesis of L-742,694, a neurokinin-1 receptor antagonist, featuring this reaction is documented.",10.1021/jacs.1c03915,2021-05-06,0.5895749288615757
Journal of the American Chemical Society,"Enantio- and Diastereoselective Stepwise Cyclization of Polyprenoids Induced by Chiral and Achiral LBAs. A New Entry to (−)-Ambrox, (+)-Podocarpa-8,11,13-triene Diterpenoids, and (−)-Tetracyclic Polyprenoid of Sedimentary Origin","An enantio- and diastereoselective stepwise cyclization of polyprenoids induced by Lewis acid-assisted chiral Brønsted acids (chiral LBAs) and achiral LBAs is described. In particular, the absolute stereocontrol in the initial cyclization of polyprenoids to form an A-ring induced by chiral LBAs and the importance of the nucleophilicity of the internal terminator in polyprenoids for the relative stereocontrol in subsequent cyclization are demonstrated. (-)-Ambrox was synthesized via the enantioselective cyclization of (E,E)-homofarnesyl triethylsilyl ether with tin(IV) chloride-coordinated (R)-2-(o-fluorobenzyloxy)-2'-hydroxy-1,1'-binaphthyl ((R)-BINOL-o-FBn) and subsequent diastereoselective cyclization with CF(3)CO(2)H.SnCl(4) as key steps. Protection of (E,E)-homofarnesol by a triethylsilyl group increased the enantioselectivity of chiral LBA-induced cyclization and both the chemical yield and diastereoselectivity in the subsequent cyclization. The enantioselective cyclization of homo(polyprenyl)arenes possessing an aryl group was also induced by (R)-BINOL-o-FBn.SnCl(4). Several optically active podocarpa-8,11,13-triene diterpenoids and (-)-tetracyclic polyprenoid of sedimentary origin were synthesized (75-80% ee) by the enantioselective cyclization of homo(polyprenyl)benzene derivatives induced by (R)-BINOL-o-FBn.SnCl(4) and subsequent diastereoselective cyclization induced by BF(3).Et(2)O/EtNO(2) or CF(3)CO(2)H .SnCl(4).",10.1021/ja0124865,2002-03-16,0.5895745785235041
Angewandte Chemie International Edition,Total Synthesis of Tubulysin U and V,"Multicomponent method: Tubulysins are among the most potent cytotoxic agents known. Now the first total synthesis of some members has been achieved by utilizing a rapid three-component reaction for the synthesis of the unusual central thiazole amino acid tubuvaline (see scheme; Boc=tert-butoxycarbonyl, Ac=acetyl), thereby opening new perspectives for anticancer drug development.",10.1002/anie.200601259,2006-10-02,0.5895710507646761
Tetrahedron,"1,3-Dioxolane C-Nucleosides: Asymmetric Synthesis of Four Stereoisomers of 2-[2-(Hydroxymethyl)-1,3-Dioxolan-5-yl)]-1,3-Thiazole-4-Carboxamide",,10.1016/00404-0399(50)17638-,1995-11-06,0.5895697131347237
Tetrahedron,"1,3-Dioxolane C-Nucleosides: Asymmetric Synthesis of Four Stereoisomers of 2-[2-(Hydroxymethyl)-1,3-Dioxolan-S-yl)-1,3-Thiazole-4-Carboxamide",,10.1016/0040-4039(95)01763-8,1995-11-01,0.5895697131347237
Organic Letters,"Synthesis of 6,8-Diazabicyclo[3.2.2]nonanes:  Conformationally Restricted Piperazine Derivatives","[formula: see text] Starting with the proteinogenic amino acid (S)-glutamate, a general method for the synthesis of 3-(piperazin-2-yl)propionic acid esters 7 with various substituents at N-4 of the piperazine ring system is presented. An intramolecular ester condensation of 7 is the key step in the formation of the 6,8-diazabicyclo[3.2.2]nonane derivatives 8-10, which are of interest as conformationally restricted piperazines.",10.1021/ol990393a,2000-03-31,0.5895640845299623
Chemical Science,Asymmetric synthesis of primary amines catalyzed by thermotolerant fungal reductive aminases,RedAm highlight their potential for wider synthetic application as well as expanding the biocatalytic toolbox available for chiral amine synthesis.,10.1039/d0sc02253e,2020-01-01,0.5895627599432591
Tetrahedron,"Synthesis and utilisation of chiral 3-hydroxy perhydropyrrolo [2,1-c] [1,4] oxazin-4-one as a novel precursor for the enantioselective synthesis of α-hydroxy carboxylic acids",,10.1016/s0040-4039(98)01530-5,1998-09-01,0.5895587824422504
European Journal of Organic Chemistry,A Second‐Generation Formal Synthesis of (+)‐Haplophytine,"Abstract In this article, a Lewis acid mediated 1,4‐addition/formal [3+2] cycloaddition reaction engaging functionalized β‐carboline and 1,4‐benzoquinone has been demonstrated. Application of this developed technology facilitated the construction of the challenging C‐9′–C‐15 quaternary center linkage in the dimeric indole alkaloid, haplophytine, and enabled the preparation of an advanced key intermediate en route to the total synthesis of this historical natural product.",10.1002/ejoc.201001629,2011-01-18,0.5895565956720351
Angewandte Chemie International Edition,Total Synthesis of Spirastrellolide F Methyl Ester—Part 1: Strategic Considerations and Revised Approach to the Southern Hemisphere,"In readiness for closure: To ensure optimal convergence in the projected total synthesis of spirastrellolide F, the building block representing the southern hemisphere was prepared with a free carboxylic acid and an enol triflate (Tf) terminus (see picture). This unusual pattern allows the 38-membered macrocyclic core of this potent antimitotic agent to be constructed, while keeping late-stage protecting-group manipulations to a minimum.",10.1002/anie.200906121,2009-12-08,0.5895485211321471
Tetrahedron,"Synthesis of novel 9-(1-iodovinyl)acridin-(2H)-one through iodine mediated cascade 6-endo-dig cyclization followed by condensation and 3,3-sigmatropic migration of 2-aminophenyl propynyl oxyenone",,10.1016/j.tetlet.2012.08.107,2012-09-03,0.5895481335464057
Angewandte Chemie International Edition,Morphological Profiling Identifies the Motor Protein Eg5 as Cellular Target of Spirooxindoles,"Abstract Oxindoles and iso‐oxindoles are natural product‐derived scaffolds that provide inspiration for the design and synthesis of novel biologically relevant compound classes. Notably, the spirocyclic connection of oxindoles with iso ‐oxindoles has not been explored by nature but promises to provide structurally related compounds endowed with novel bioactivity. Therefore, methods for their efficient synthesis and the conclusive discovery of their cellular targets are highly desirable. We describe a selective Rh III ‐catalyzed scaffold‐divergent synthesis of spirooxindole–isooxindoles and spirooxindole–oxindoles from differently protected diazooxindoles and N ‐pivaloyloxy aryl amides which includes a functional group‐controlled Lossen rearrangement as key step. Unbiased morphological profiling of a corresponding compound collection in the Cell Painting assay efficiently identified the mitotic kinesin Eg5 as the cellular target of the spirooxindoles, defining a unique Eg5 inhibitor chemotype.",10.1002/anie.202301955,2023-03-16,0.5895442357772277
Organic Letters,Metal-Free C–H Functionalization and Aromatization Sequence for the Synthesis of 1-(Indol-3-yl)carbazoles and Total Synthesis of 7-Bromo-1-(6-bromo-1<i>H</i>-indol-3-yl)-9<i>H</i>-carbazole,"An operationally simple, metal-free, cost-effective, and mild oxidative cross-coupling protocol for the synthesis of 1-indolyl tetrahydrocarbazoles to afford 1-(indol-3-yl)carbazoles is developed. N-Chlorosuccinimide is used as a mild oxidant for the functionalization of the 1-position of tetrahydrocarbazoles, aromatization of which furnished 1-(indol-3-yl)carbazoles in good to moderate yields without employing protection/deprotection strategy. A naturally rare dibromo 1-(indol-3-yl)carbazole alkaloid was synthesized for the first time in two steps with an overall yield of 64% by applying the same methodology.",10.1021/acs.orglett.8b03848,2019-01-24,0.5895437945957961
Organic Process Research & Development,"Novel, Practical, and Efficient Process for the Preparation of 4,5-Dichloroindole","A novel, practical, and efficient three-step process for the preparation of 4,5-dichloroindole 5, an important starting material for a wide range of fine chemicals and pharmaceuticals has been developed. The process comprises nitration of commercially available 2,3-dichlorobenzaldehyde 1, a telescopic process for the Henry reaction, and subsequently reductive cyclization of resulting o,β-dinitrostyrene intermediate 4 into 4,5-dichloroindole using iron powder in methanol and acetic acid by the Nenitzescu reaction. The large-scale applicability of this novel and improved process has been successfully demonstrated on a multikilogram scale by carrying multiple batches to produce 5 in 67–70% yields and 96–98% purity without column chromatography. The reactions are facile, safe, and easy to scale up.",10.1021/acs.oprd.2c00212,2022-10-31,0.5895348269797092
Tetrahedron,ZnBr2 catalyzed sequential A3-coupling and intramolecular cyclization: One-pot synthesis of 3-aminofurans,,10.1016/j.tetlet.2025.155718,2025-06-19,0.5895330002422636
Organic Letters,A Short Stereoselective Total Synthesis of the Fusarium Toxin Equisetin,"A short stereoselective synthesis of the fusarium toxin equisetin, an N-methylserine-derived acyl tetramic acid and potent inhibitor of HIV-1 integrase enzyme, is described using as the key step a stereoselective lithium perchlorate mediated intramolecular Diels-Alder reaction of a fully conjugated E,E,E-triene with a trisubstituted gamma,delta-unsaturated beta-ketothioester.",10.1021/ol006493u,2000-10-21,0.5895281605664279
Angewandte Chemie International Edition,Total Synthesis of Halipeptin A: A Potent Antiinflammatory Cyclic Depsipeptide,"The antiinflammatory drug halipeptin A (1) is a 17-membered cyclic depsipeptide made up of L-alanine, α-methylcysteine, decanoic acid, and isoleucine residues. Key steps in its total synthesis, which helped to confirm the stereochemistry of the natural product, include a borane-mediated aldol reaction and an asymmetric aza-Claisen rearrangement.",10.1002/anie.200461239,2004-12-15,0.5895237113925581
Tetrahedron,"Alternative synthesis of TTF donors with a dioxolane ring, and synthesis of their dithiolane and oxathiolane analogues",,10.1016/s0040-4039(98)01679-7,1998-10-01,0.5895225178431682
Organic Process Research & Development,Early Clinical Development of Lufotrelvir as a Potential Therapy for COVID-19,"Lufotrelvir was designed as a first in class 3CL protease inhibitor to treat COVID-19. Development of lufotrelvir was challenged by its relatively poor stability due to its propensity to epimerize and degrade. Key elements of process development included improvement of the supply routes to the indole and lactam fragments, a Claisen addition to homologate the lactam, and a subsequent phosphorylation reaction to prepare the prodrug as well as identification of a DMSO solvated form of lufotrelvir to enable long-term storage. As a new approach to preparing the indole fragment, a Cu-catalyzed C-O coupling using oxalamide ligands was demonstrated. The control of process-related impurities was essential to accommodate the parenteral formulation. Isolation of an MEK solvate followed by the DMSO solvate ensured that all impurities were controlled appropriately.",10.1021/acs.oprd.2c00375,2023-02-03,0.5895218051001265
Organic Letters,Halichondrin B:  Synthesis of a C1−C14 Model via Desymmetrization of (+)-Conduritol E,"[reaction: see text] A model C1-C14 segment (1) of halichondrin B was synthesized from (+)-conduritol E (7) in 18 steps and 2.9% overall yield. Key features of the synthesis include the novel ozonolytic desymmetrization of C(2)-symmetric diol 6, the early-stage construction of the C-ring which accompanies installation of the crucial C12 stereocenter, and the use of an enol ether C14-ketone surrogate as a precursor to the CDE-""caged"" ketal.",10.1021/ol027389a,2003-01-24,0.5895201742327492
Tetrahedron,Totally diastereoselective synthesis of a new chiral quinoline diazaphospholidine ligand and its derivatives,,10.1016/s0040-4039(02)00691-3,2002-05-01,0.5895107002134607
Organic Process Research & Development,Convergent Synthesis of Menaquinone-7 (MK-7),"A practical synthesis of menaquinone-7 (MK-7, vitamin K 2 ) in the all- trans form was designed. Stereoselective synthesis of MK-7 was achieved through a “1 + 6” convergent strategy by condensation of two building blocks, menadione monoprenyl derivative (fragment “1”) with hexaprenyl bromide (fragment “6”, 82%). Pd-catalyzed desulfonation with LiEt 3 BH (78%) was followed by oxidation of the hydroquinone moiety using ammonium cerium(IV) nitrate (72%). The major challenge in our methodology was the preparation of all- trans hexaprenyl bromide by coupling of two triprenyl units derived from trans,trans -farnesol. Manufacturing on a pilot scale was accomplished through our approach. The scalable method was designed especially for a large, kilogram-scale production from easily available intermediates. Furthermore, the proposed methodology avoids many chromatographic purifications and allows for a relatively cost-effective manufacturing. Moreover, our synthesis yielded high-purity (99.9%) final product MK-7, which can be used as a dietary supplement as well as an active pharmaceutical ingredient.",10.1021/acs.oprd.6b00037,2016-05-06,0.5895098991839193
Journal of Organic Chemistry,Stereopentads Derived from a Sequence of Mukaiyama Aldolization and Free Radical Reduction on α-Methyl-β-alkoxy Aldehydes: A General Strategy for Efficient Polypropionate Synthesis,"In a stereodivergent manner, all 16 diastereomeric stereopentads 7-22 were synthesized starting with alpha-methyl-beta-alkoxy aldehydes 25 and 27. We designed an approach based on a sequence of a Mukaiyama aldolization with enoxysilane 24 followed by a hydrogen transfer reaction. Recent advancements concerning these reactions are described, and novel key intermediates are characterized in the aldol step. The synthesis of C(1)-C(11) fragment 60 of zincophorin, which contains a synthetically challenging stereopentad unit, is described attesting the usefulness of our strategy.",10.1021/jo8021583,2008-12-08,0.5895096939187244
Tetrahedron,"Total synthesis of progesterone receptor ligands, (−)-PF1092A, B and C",,10.1016/s0040-4039(97)00042-7,1997-02-01,0.5895039255488246
Journal of the American Chemical Society,Total Synthesis of Euphorbialoid A,"Euphorbialoid A ( 1 ) belongs to the rare diterpenoid family of premyrsinanes and exhibits potent anti-inflammatory effects. The 5/7/6/3-membered carbocycle (ABCD-ring) of 1 contains 11 contiguous stereocenters and seven oxygen-containing functional groups. Moreover, four of the six hydroxy groups of 1 are concentrated in the southern sector and flanked by four structurally different acyl groups. The dense array of various functional groups with disparate reactivities on the tetracyclic ABCD-ring presents a daunting challenge for the chemical synthesis of 1 . As a reflection of its formidable complexity, synthesis of 1 or any other premyrsinane diterpenoids has not yet been reported. Here, we devised a novel strategy comprising two stages and achieved the first total synthesis of 1 (35 steps as the longest linear sequence). In the first stage, the ABCD-ring was expeditiously assembled by integrating three powerful transformations: (1) Pt-doped TiO 2 -catalyzed radical coupling to attach a northern chain to a 6/3-membered CD-ring, (2) Pd-catalyzed decarboxylative asymmetric allylation to construct a quaternary carbon with a southern chain, and (3) a Co-mediated Pauson–Khand reaction to cyclize the two chains into the 5/7-membered AB-ring. In the second stage, three-dimensional structures of the ABCD-ring intermediates were utilized to stereoselectively fabricate the A-ring and site-selectively append the four different acyl groups. In the present total synthesis, we revealed the significance of orchestrating the multistep reaction sequence and incorporating cyclic protective groups. The overall strategy and tactics provide new insights into designing synthetic routes to premyrsinanes and densely oxygenated terpenoids decorated with diverse acyl groups.",10.1021/jacs.4c14520,2024-12-02,0.589503878860098
Organic Letters,Asymmetric Total Synthesis of Anti-HBV Drug Entecavir: Catalytic Strategies for the Stereospecific Construction of Densely Substituted Cyclopentene Cores,"We have successfully accomplished a catalytic asymmetric total synthesis of entecavir, a first-line antihepatitis B virus medication. The pivotal aspect of our strategy lies in the utilization of a Pd-catalyzed enyne borylative cyclization reaction, enabling the construction of a highly substituted cyclopentene scaffold with exceptional stereoselectivity. Additionally, we efficiently accessed the crucial 1,3-diol enyne system early in our synthetic route through a diarylprolinol organocatalyzed enantioselective cross-aldol reaction and Re-catalyzed allylic alcohol relocation. By strategically integrating these three catalytic protocols, we established a practical pathway for acquiring valuable densely heteroatom-substituted cyclopentene cores.",10.1021/acs.orglett.4c01669,2024-05-29,0.589494680262567
Journal of Organic Chemistry,Stereoselective Synthesis of P-Chirogenic Dibenzophosphole–Boranes via Aryne Intermediates,"A new aryne-mediated tandem cross-coupling/P-cyclization sequence starting from tertiary phosphine-boranes and 1,2-dibromobenzenes is reported. P-chirogenic dibenzophospholes become accessible in a regio-, chemo-, and diastereoselective way.",10.1021/jo3009098,2012-06-18,0.5894832761951881
Organic Letters,Total Synthesis of (+)-Hyacinthacine A<sub>1</sub> Using a Chemoselective Cross-Benzoin Reaction and a Furan Photooxygenation–Amine Cyclization Strategy,"We report the shortest synthesis of glycosidase inhibitor (+)-hyacinthacine A 1 using a highly chemoselective N-heterocyclic carbene-catalyzed cross-benzoin reaction as well as a furan photooxygenation–amine cyclization strategy. This is the first such cyclization on a furylic alcohol, an unprecedented reaction due to the notorious instability of the formed intermediates. The photooxygenation strategy was eventually incorporated into a three-step one-pot process that formed the requisite pyrrolizidine framework of (+)-hyacinthacine A 1 .",10.1021/acs.orglett.1c00090,2021-02-04,0.5894827406476829
Journal of Organic Chemistry,Diastereoselective Synthesis of the Monosaccharide Kedarosamine and Incorporation in an Analogue of the Enediyne Kedarcidin Chromophore,"Kedarcidin chromophore, as with most enediyne antitumor antibiotics, contains unusual monosaccharide moieties. Synthesis of one of these moieties, the 2,4,6-trideoxy-4-dimethylaminohexose kedarosamine, from d -threonine and incorporation into an analogue of kedarcidin chromophore ( 1 ) is described herein. Conversion of d -threonine into allyl ketone 7 and stereoselective reduction by using tetramethylammonium triacetoxyborohydride for intramolecular hydride delivery were key steps in the preparation of kedarosamine. A thioglycoside derivative of kedarosamine ( 12 ) was found to be less efficient as a glycosyl donor, whereas a 1- O -acetate ( 15 ) gave the desired α-glycoside exclusively in 60−80% yield when treated with borontrifluoride etherate. Use of a Cbz instead of a Fmoc protecting group for the C-4 amino group of kedarosamine was essential for the successful preparation of analogue 1 . Finally, dimethylation of the amino group at C-4 of kedarosamine was found to require careful adjustment of the reaction conditions in order to avoid byproduct formation.",10.1021/jo971380i,1998-01-01,0.5894750685895142
Synlett,Selectfluor-Mediated Tandem Cyclization of Enaminones for the Synthesis of 3-Fluorochromones,"An efficient synthesis of various 3-fluorochromones (3-fluoro-4H-chromene-4-ones) from enamino ketones by using Selectfluor is described. The key step in the synthesis involves tandem fluorination and cyclization to form 3-fluorochromones in good yields. The significant features of this method include simple operational procedures, a high purity of the product, and excellent regioselectivity.",10.1055/s-0039-1691489,2019-11-20,0.5894743004902647
Synlett,"Diastereoselective Synthesis of Highly Substituted 2,5-Diaminohexanes via Nitrile Oxide Cycloaddition to a Vinylogous Amino Acid","All articles of this category A novel route to 1,6-disubstituted 2,5-diamino-3-hydroxy-4-hydroxymethylhexanes is described. N -protected ethyl (2 E ,4 S )-4-amino-5-phenylpent-2-enoate undergoes cycloaddition with nitrile oxides producing the syn and anti isomers of ethyl isoxazoline-4-carboxylates in a 2:1 ratio. The individual isomers are converted into 1,4-diaminohexanes via chemoselective ester reduction with lithium aluminum hydride, followed by highly diastereoselective reductive cleavage of the isoxazoline ring with borane-dimethylsulfide complex. vinylogous amino acid - nitrile oxide - isoxazoline - reduction - borane-dimethylsulfide complex",10.1055/s-1996-5670,2000-12-31,0.5894733574800626
Journal of Organic Chemistry,Improved Synthesis of an Ethereal Tetraamine Core for Dendrimer Construction,A new route to a pentaerythritol-based tetraamine is delineated and subsequently contrasted to a previous report. Access to the pure tetraamine is facilitated by the smooth reduction of its tetraazide precusor. Characterization includes the preparation of a 4:1 Zn-tetraphenylporphyrin/tetraamine complex.,10.1021/jo025625p,2002-04-26,0.5894729256920844
Angewandte Chemie International Edition,Cover Picture: Total Synthesis of Palau’amine (Angew. Chem. Int. Ed. 6/2010),"The exotic natural product palau'amine contains a number of rare structural features, just like the extraordinary biodiversity found in the island nation of Palau. As such, palau'amine has been the most actively pursued alkaloid among synthetic chemists in the 21st century, and its first total synthesis is now described by P. S. Baran and co-workers in their Communication on page 1095 ff. The successful route features transformations on unprotected intermediates, cascade reactions, and a remarkable finale involving a transannular cyclization to forge the critical bond. Cover designed by Paul Krawczuk; photograph courtesy of iStockphoto.com/clumpner.",10.1002/anie.200907224,2010-01-13,0.5894725194486302
Synthesis,"New Route to Dimethylnaphthalenes Involving Cyclization of Ylidenemalonodinitriles and Ethyl Ylidenecyanoacetates; Part 2<sup>1</sup>. Synthesis of 1,7-, 2,6-, and 2,7-Dimethylnaphthalene",,10.1055/s-1983-30425,1983-01-01,0.5894714558661591
Angewandte Chemie International Edition,Total Synthesis of (±)-Halomon by a Johnson-Claisen Rearrangement,"The total synthesis of the polyhalogenated antitumour agent halomon (1) was accomplished with two novel transformations as key steps: a Johnson-Claisen rearrangement of a dichlorinated alkene for the preparation of the tertiary chlorinated C3 and a new rearrangement of bromohydrins for the regiospecific introduction of the bromine and chlorine atoms on C6 and C7, respectively.",10.1002/(sici)1521-3773(19980817)37:15<2085::aid-anie2085>3.0.co;2-j,1998-08-17,0.5894576509988199
Journal of the American Chemical Society,Catalysis-Enabled 13-Step Total Synthesis of (−)-Peyssonnoside A,"We report a 13-step enantioselective and stereoselective total synthesis of (-)-peyssonnoside A, a unique diterpene glucoside with a rare and highly congested pentasubstituted cyclopropane and promising antimicrobial activity. Among the 10 steps to synthesize (-)-peyssonnosol, the aglycone of (-)-peyssonnoside A, eight transition-metal-catalyzed transformations enabled the construction of all new C-C bonds and stereocenters without involving any protecting groups. Notably, a palladium-catalyzed dearomative cyclization was used to build the C-6 spiro all-carbon quaternary center, and a counterintuitive hydrogen atom transfer (HAT)-initiated reductive olefin cross-coupling was realized to forge the pentasubstituted cyclopropane ring with excellent stereoselectivity.",10.1021/jacs.2c09919,2022-10-24,0.5894564179533085
Organic Letters,"Total Synthesis and Structural Revision of the 6,11-Epoxyisodaucane Natural Sesquiterpene Using an Anionic 8π Electrocyclic Reaction","A new synthetic strategy that forms a seven-membered carbocycle using an anionic 8π electrocyclic reaction facilitated the first total synthesis of the 6,11-epoxyisodaucane natural sesquiterpene in 9.0% yield over 10 steps in the longest linear sequence. The misassigned proposed stereochemistry was corrected by the synthesis of both the proposed structure and its C6 epimer. In addition, the 5-7-fused ring system was concisely constructed by tandem decyanation/five-membered-ring formation from an epoxynitrile.",10.1021/acs.orglett.2c03068,2022-10-21,0.5894557748951464
Tetrahedron,A one-pot synthesis of tetrahydroisoquinolin-4-ols via a novel acid-catalyzed rearrangement of 5-aryloxazolidines,,10.1016/j.tetlet.2013.02.087,2013-03-08,0.5894525156143945
Journal of the American Chemical Society,Total Syntheses of Rhodomollins A and B,"The first and asymmetric total syntheses of rhodomollins A and B, two rhodomollane type grayanoids featuring a d -homograyanane carbon skeleton and an oxa -bicyclo[3.2.1] core, were accomplished via a convergent strategy. A Stille coupling and a lithium-halogen exchange/intramolecular nucleophilic addition to the aldehyde sequence were employed to assemble two enantioenriched fragments. The oxa -bicyclo[3.2.1] core was achieved through an intramolecular S N 2 substitution of cyclic sulfate of 1,2-diols (Williamson ether synthesis). The A ring oxidation states were adjusted by a Payne/Meinwald rearrangement sequence and subsequent redox transformations.",10.1021/jacs.3c12249,2023-11-28,0.5894457232807203
Tetrahedron,"Synthesis of sulfobacin A and B, new sulfonolipids isolated from Chryseobacterium sp.",,10.1016/s0040-4039(98)01456-7,1998-09-01,0.5894456965861926
Synlett,Intramolecular Ene-Based Approach to Furofuran Lignans: Total Synthesis of Neopaulownin,"All articles of this category The lignan neopaulownin was synthesized in eight steps in 20% overall yield from piperonal by employing the type 5-(3,4) ene cyclization reaction of allylic (γ-aryl)propargyl ether as the key step.",10.1055/s-1993-22416,1993-01-01,0.589441133230527
Synlett,Lankacidin Synthesis: Synthesis of the Lactone Fragment and an Improved Procedure for Stereoselective Acylation of a Chiral β-Lactam,"(opens in new window) Buy Article (opens in new window) Permissions and Reprints (opens in new window) All articles of this category (opens in new window) A synthesis of 6-membered lactone 17 , the C(14)-C(6) fragment of lankacidin C ( 1 ), using an improved procedure for ß-lactam acylation is described, together with methodology for introduction of the C(10)-(13) diene.",10.1055/s-1990-21226,1990-01-01,0.5894394297372884
Organic Letters,Enantioselective Synthesis of Saframycin A and Evaluation of Antitumor Activity Relative to Ecteinascidin/Saframycin Hybrids,"[formula: see text] A short synthesis of saframycin A is described which begins with a readily available intermediate previously utilized for the total synthesis of ecteinascidin 743. A key step in this synthesis is the use of 1-fluoro-3,5-dichloropyridinium triflate to oxidize a phenolic ring to a 1,4-benzoquinone unit while simultaneously cleaving a methoxymethyl ether of a different phenolic ring to the corresponding phenol (4-->5). The common intermediate (2) for the synthesis of saframycin A (1) and ecteinascidin 743 also allowed the synthesis of two hybrids of these structures (6 and 7). Whole cell bioassays for antitumor activity using lung, colon, melanoma, and prostate-derived tumor cell lines allowed a clear correlation of structure with biological activity in this series.",10.1021/ol990553i,1999-05-17,0.5894388151791884
Synthesis,"An Efficient Synthesis of 3,3′-Bipiperidines Using an ROM/RCM Metathesis Sequence: Extension to Oxygenated Analogues","A short and efficient diastereoselective synthesis of 3,3′-bipiperidine and 3,3′-bis(1,2,3,6-tetrahydropyridine) was accomplished using a tandem ring-opening metathesis/ring-closing metathesis (ROM/RCM) sequence as a key step. This strategy has been extended to the synthesis of the oxygenated analogues.",10.1055/s-0034-1378663,2014-08-28,0.5894313783572672
Organic Letters,Development of a Strategy for the Asymmetric Synthesis of Polycyclic Polyprenylated Acylphloroglucinols via <i>N</i>-Amino Cyclic Carbamate Hydrazones: Application to the Total Synthesis of (+)-Clusianone,A broadly applicable asymmetric synthetic strategy utilizing N-amino cyclic carbamate alkylation that provides access to the various stereochemical permutations of a common structural motif found in many polycyclic polyprenylated acylphloroglucinols is described. The utility of this methodology is demonstrated through the first asymmetric total synthesis of the antiviral agent (+)-clusianone.,10.1021/ol1022728,2010-10-26,0.5894303179765971
Synlett,Development of a Stereospecific Strategy for the Total Synthesis of Diplodialide C and Formal Synthesis of (–)-Curvularin,"Abstract A concise and efficient stereospecific approach for the total synthesis of diplodialide C (R,R and S,S isomers) has been demonstrated using chiral homoglycidol and propylene oxide as a source of starting material. Further oxidized ketolide product derived from diplodialide C (S,S isomer) was applied to the formal synthesis of (–)-curvularin following reported known literature.",10.1055/s-0043-1775057,2024-09-19,0.5894278686780803
Organic Letters,IMDA-Radical Cyclization Approach to (+)-Himbacine,"[reaction: see text] A formal total synthesis of the selective muscarinic receptor antagonist himbacine is presented. Key C-C bond-forming steps include an intramolecular Diels-Alder reaction, Stille coupling reactions, and a 6-exo-trig acyl radical cyclization to a conjugated enyne. An unexpected secondary alcohol to chloride conversion is witnessed during attempted thionocarbonate formation.",10.1021/ol0353058,2003-09-09,0.5894244806811076
Tetrahedron,"Methiodide approach to the synthesis of 3-[2-(dimethylamino)ethyl]-5-[(1,1-dioxo-5-methyl-1,2,5-thiadiazolidin-2-yl)methyl]-1H-indole and analogues",,10.1016/s0040-4039(00)60662-7,1993-09-01,0.5894229541460204
European Journal of Organic Chemistry,Synthesis of a C–N Axially Chiral <i>N</i>‐Arylisatin through Asymmetric Intramolecular <i>N</i>‐Arylation,"Abstract We describe the first synthesis of an enantiomerically pure C–N axially chiral N ‐arylisatin from the corresponding N ‐aryloxindole, which was synthesized by an asymmetric intramolecular Buchwald–Hartwig N ‐arylation. This novel isatin would be a potentially versatile synthetic intermediate for a variety of 3,3‐disubstituted oxindoles bearing a C3 stereogenic center.",10.1002/ejoc.201500593,2015-06-24,0.5894227621659643
Tetrahedron,Synthesis of a B-homo-6-azaandrost-4-ene-3-one as a novel steroidal 5α-reductase inhibitor,,10.1016/s0040-4039(00)76634-2,1994-05-01,0.5894123034415664
European Journal of Organic Chemistry,"Short, Convergent Synthesis of Locked Retinals",Abstract We report a short and convenient synthesis of two configurationally locked retinals that are important for applications in the context of optogenetics. The C11–C15 cyclopentyl fragments of both retinals were obtained by palladium‐catalysed alkoxycarbonylation and merged with the rest of the carbon skeleton through Wittig olefination. The preparation of the required and known ylide precursor was revisited and optimised. This synthetic route enables gram‐scale preparation of both retinal derivatives.,10.1002/ejoc.201403006,2014-09-29,0.5894044232099078
European Journal of Organic Chemistry,Asymmetric Synthesis of Iridoid Derivatives Using Resolved 2‐Phenylindoline as a Chiral Auxiliary,"Abstract An asymmetric synthetic route to cis , cis ‐nepetalactol (component of the sex pheromone for the hop aphid, Phorodon humuli ) is presented. 2‐Phenylindoline was resolved to provide a chiral auxiliary for the cycloaddition of oxocitral. The resolution was made by chromatographic separation of the diastereomers of the urea derivative made from 2‐phenylindoline and with ( R )‐(+)‐α‐methylbenzyl isocyanate, followed by reductive cleavage of the isolated diasteromers using diborane. The cycloaddition of oxocitral using ( S )‐2‐phenylindoline yielded an enantiopure product after chromatography. Hydrolysis of the cycloaddition adduct yielded gastrolactol ( 3 ). As gastrolactol is a versatile synthon for the synthesis of iridoids, the overall procedure provides a general asymmetric route to elaborated iridoids. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2009)",10.1002/ejoc.200800440,2008-11-04,0.5893996309495491
Tetrahedron,A short and efficient total synthesis of the cytotoxic (+)-goniodiol and (+)-9-deoxygoniopypyrone,,10.1016/s0040-4039(98)01562-7,1998-10-01,0.5893996202024882
Journal of Organic Chemistry,New Efficient Procedure for the Use of Diethoxyphosphoryl as a Protecting Group in the Synthesis of Polyazamacrocycles. Preparation of Polyazacyclophanes Derived from Resorcinol,The synthesis of polyazamacrocycles containing an electron-rich aromatic subunit derived from resorcinol is described. The reported synthetic procedure is based on the use of diethoxyphosphoryl (Dep) as an amine protecting group. The new conditions employed for the cyclization reaction allow for a generalized use of Dep in the synthesis of polyazamacrocycles.,10.1021/jo0353381,2003-11-27,0.5893977911183923
Tetrahedron,Efficient palladium catalyzed synthesis of heteroaromatic sulfoxides,,10.1016/j.tetlet.2007.07.165,2007-07-31,0.5893951274459016
Tetrahedron,An efficient palladium catalyzed synthesis of 2-arylbenzothiazoles,,10.1016/j.tetlet.2003.09.138,2003-10-18,0.5893951274459016
Angewandte Chemie International Edition,Ionization of O3 in Excess N2: A New Route to N2O via Intermediate N2O3+ Complexes,,10.1002/1521-3773(20010518)40:10<1938::aid-anie1938>3.3.co;2-h,2001-05-18,0.5893884740010283
Journal of Organic Chemistry,An Enantioselective Convergent Route to Pamamycin 621A,"An effective approach to the total synthesis of natural antibiotic pamamycin 621A is described, in which the stereogenic centers at the C-13 and C-15 were taken from a chiral building block derived from the inexpensive D-glucolactone while all others (except the C-10) were installed via chiral auxiliary-induced asymmetric Evans/Crimmins aldol reactions. In the synthesis of the smaller/lower fragment, an antiselective Evans aldol condensation was found to occur only if a stoichiometric (rather than catalytic as reported in the literature) amount of magnesium chloride was present. A previously unknown effect of the steric bulkiness of the pyridine base employed on the stereochemical outcome of the formation of the THF ring in the presence of a chiral auxiliary was also observed. The THF rings in the larger/upper fragment were similarly synthesized with a high level of stereoselectivity from a linear precursor carrying a chiral auxiliary via intramolecular O-alkylations, most notably even under acidic conditions. The basic dimethylamino functionality at the C-15 was installed at the final stage of the whole synthesis, with those otherwise unavoidable side reactions in the conversion of the azido group effectively circumvented through using a very mild yet largely forgotten tributyltin reduction protocol.",10.1021/jo100774n,2010-07-02,0.5893820351206055
Synthesis,Stereodivergent Synthesis of the Four Stereoisomers of Diethyl 4-Hydroxyphosphopipecolate from Ethyl (R)-4-Cyano-3-hydroxybutanoate,"Abstract The stereodivergent synthesis of all four stereoisomers of diethyl 4-hydroxyphosphopipecolate from the commercial chiral building block ethyl (R)-4-cyano-3-hydroxybutanoate is described. Key steps in the synthesis of the target compounds involve the triethyl phosphite nucleophilic addition to chiral N-acyliminium ion easily obtained from (R)-4-hydroxypiperidin-2-one, giving diethyl (2R,4R)- and (2S,4R)-4-hydroxyphosphopipecolate diastereoisomers, easily separable by column chromatography followed by the 4-hydroxy epimerization through a sequential oxidation and highly diastereoselective reduction strategy, affording the diethyl (2R,4S)- and (2S,4S)-4-hydroxyphosphopipecolate, respectively, consistent with our recently found results. All synthesized compounds were thoroughly characterized.",10.1055/a-2329-4214,2024-05-17,0.5893765285945819
Journal of the American Chemical Society,Unified Total Synthesis of Stemoamide-Type Alkaloids by Chemoselective Assembly of Five-Membered Building Blocks,"A unified total synthesis of stemoamide-type alkaloids is reported. Our synthetic approach features the chemoselective convergent assembly of five-membered building blocks via stemoamide as the common precursor to tetracyclic natural products. The synthesis consists of two successive coupling reactions of the three five-membered building blocks. The first coupling reaction is the vinylogous Michael addition/reduction sequence, which enables the gram-scale synthesis of stemoamide. The second coupling reaction is a chemoselective nucleophilic addition to stemoamide. While the lactone-selective nucleophilic addition to stemoamide affords saxorumamide and isosaxorumamide, the lactam-selective reductive nucleophilic addition leads to the formation of stemonine. Both chemoselective nucleophilic additions enable direct modification of stemoamide, resulting in highly concise and efficient total syntheses of the stemoamide-type alkaloids.",10.1021/jacs.7b10944,2017-11-28,0.5893759355493173
Synlett,"A Short Enantioselective Synthesis of Protected<scp>l</scp>-3-Hydroxy-4-methoxy-5-methyl Phenylalanine and its Corresponding Aldehyde - A Common Subunit of Ecteinascidin-743, Safracin and Congeners",An asym. synthesis of appropriately protected L-3-hydroxy-4-methoxy-5-Me phenylalanine from 3-methylcatechol is described featuring a key enantioselective alkylation step. [on SciFinder (R)],10.1055/s-2004-817763,2004-01-01,0.5893691790970678
Synlett,Stereoselective Formation ofa β-Lactam Fused Oxathiazepin: A Synthetic Approachto Eudistomins,A synthetic approach to eudistomin via a β-lactam fused bicyclic oxathiazepin intermediate is described. A β-lactam fused oxathiazepin derivative was synthesized by intramolecular 7-membered oxime ether formation and subsequent face-selective reduction of the C-N double bond. A fully functionalized ortho-alkenylphenylthioanilide bearing oxathiazepin ring was then prepared and construction of the indole skeleton under several radical-mediated conditions was examined.,10.1055/s-2003-38378,2003-01-01,0.589367328375306
Synthesis,Synthesis of Highly Substituted 2-Imidazolines through a Three-Component Coupling Reaction,"A simple strategy for the synthesis of highly substituted 2-imidazolines starting from terminal alkynes, sulfonyl azides, and N-unsubstituted aziridines via two steps with high regioselectivity is described.",10.1055/s-2007-1000818,2007-12-20,0.5893641647984478
Journal of Organic Chemistry,"Formal Total Syntheses of (+)- and (−)-Aspidophytine from a Common, Homochiral Precursor","A formal total synthesis of (−)-aspidophytine ( 2 ), a key substructure associated with the heterodimeric indole alkaloid haplophytine ( 1 ) and itself a natural product, has been established by employing the homochiral and enzymatically derived cis -1,2-dihydrocatechol 8 as a starting material. Specifically, compound 8 has been converted into the pentacyclic product 26, an advanced intermediate associated with a previously reported synthesis of aspidophytine ( 2 ). Simple modifications to the reaction sequence have also allowed for the identification of a synthetic pathway leading from dihydrocatechol 8 to (+)-aspidophytine ( ent - 2 ).",10.1021/acs.joc.2c01864,2022-10-04,0.5893604300607682
Synlett,Efficient Synthesis of Highly Enantioenriched Δ1-Pyrrolines,"A general and efficient asymmetric synthesis of Δ 1 -pyrrolines by a one-pot nitro-reduction, cyclization, and dehydration of ( R , E )-1,5-diphenyl-3-(nitromethyl)-5-pent-4-en-1-ones with iron and aqueous hydrochloric acid has been developed. The Δ 1 -pyrrolines were obtained with excellent enantioselectivities (up to 99%) and high yields (up to 83%).",10.1055/s-0034-1380144,2015-02-17,0.5893602885250703
Journal of the American Chemical Society,Gram-Scale Total Synthesis of Illisimonin A,"Illisimonin A, a structurally complex sesquiterpenoid isolated from the Illicium genus, possesses a 5/5/5/5/5 pentacyclic scaffold featuring seven contiguous, fully substituted chiral quaternary carbon centers. Herein, we report a gram-scale total synthesis of (±)-Illisimonin A achieved in 14 steps. The strategic approach features several key transformations: (1) a pentafulvene-involved intramolecular [6 + 2] cycloaddition that rapidly assembles the linear 5/5/5 tricyclic core, (2) a pentafulvene-involved intramolecular alkylation enabling polycyclic framework construction, (3) a nitroso-Diels-Alder reaction for precise oxidation state installation, and (4) a late-stage Ru-catalyzed oxidative lactonization.",10.1021/jacs.5c07921,2025-06-26,0.589360036346836
Tetrahedron,Efficient total synthesis of three alpinoids via the Au(I)-catalyzed Meyer-Schuster rearrangement,,10.1016/j.tetlet.2022.154015,2022-07-14,0.5893511800580469
Organic Letters,Total Synthesis of (+)-Rubellin C,"The rubellins are a family of stereochemically complex anthraquinoid heterodimers containing an unprecedented chemical scaffold. Although the rubellins have been known for over three decades, no total synthesis has been achieved since their discovery. Their topology is characterized by a 6-5-6 fused ring system, five neighboring stereocenters including a quaternary center all in a convoluted core, and an anthraquinone nucleus. The rubellin architecture has been shown to inhibit and reverse the aggregation of tau protein, a therapeutically relevant target for Alzheimer's disease. Herein, we describe the first stereoselective synthesis of a member of the family, (+)-rubellin C, in 16 steps. Strategic disconnections allow expedient construction of stereochemical and topological intricacy in a short sequence of borylative and transition metal-catalyzed steps.",10.1021/acs.orglett.0c02127,2020-07-30,0.5893466896022915
Journal of Organic Chemistry,"Biomimetic Construction of the Hydroquinoline Ring System. Diastereodivergent Enantioselective Synthesis of 2,5-Disubstituted <i>cis</i>-Decahydroquinolines","The straightforward enantioselective construction of the hydroquinoline ring system from 1,5-polycarbonyl derivatives, using (R)-phenyglycinol as a chiral latent form of ammonia, is reported. The process mimics the key steps believed to occur in nature in the biosynthesis of amphibian decahydroquinoline alkaloids. Diastereodivergent routes to enantiopure cis-2,5-disubstituted decahydroquinolines, including the alkaloid pumiliotoxin C (cis-195A), are developed.",10.1021/jo1005894,2010-04-30,0.5893410747400346
Journal of Organic Chemistry,Anionic Cyclization Approach toward Perhydrobenzofuranone:  Stereocontrolled Synthesis of the Hexahydrobenzofuran Subunit of Avermectin,"A facile anionic cyclization approach toward stereocontrolled synthesis of the hexahydrobenzofuran subunit 3 of avermectin is described. As a model study, treatment of iodo compound 7 with n-BuLi at -100 degrees C effected metal-halogen exchange and subsequent anionic cyclization to afford perhydrobenzofuranone 8. For the total synthesis of subunit 3, compound 9 was dihydroxylated to give diol 10. Protection of the hydroxyl groups of diol 10 gave compound 11. Ketone 11 was then converted into the required enone 12 using Saegusa's protocol. On iodination followed by Luche reduction, enone 12 yielded alpha-iodo allylic alcohol 14, which on alkylation afforded ether 15. Conversion of the ester unit of 15 into a Weinreb amide group followed by anionic cyclization gave enone 17. 1,4-Addition of (MeOCH(2))(2)CuCNLi(2) to enone 17 followed by cleavage of the acetal unit afforded ketone 19. Preferential acetylation of the secondary alcoholic function of 19 afforded compound 20. The stereochemistry of 20 is confirmed by single-crystal X-ray analysis. Elimination of HOAc from 20 gave the crucial olefin 21. Hydrolysis of the acetate unit of 21 followed by protection of the resulting alcoholic function yielded tert-butyldimethylsilyl ether 23. Introduction of a hydroxyl group at the ring junction of 23, using Davis's procedure, finally afforded the hexahydrobenzofuran subunit 3.",10.1021/jo010853p,2002-01-10,0.5893405934527696
Journal of Organic Chemistry,Concise Synthesis of Anti-HIV-1 Active (+)-Inophyllum B and (+)-Calanolide A by Application of (−)-Quinine-Catalyzed Intramolecular Oxo-Michael Addition,"(-)-Quinine-catalyzed intramolecular oxo-Michael addition (IMA) of 7-hydroxy-5-methoxy-8-tigloylcoumarins was developed for the enantioselective construction of 2,3-dimethyl-4-chromanone systems in the context of the asymmetric synthesis of anti-HIV-1 active Calophyllum coumarins. Combination of the IMA and MgI(2)-assisted demethylation of the 5-methoxy group along with isomerization of the formed chromanone systems as key steps successfully led to the concise synthesis of (+)-inophyllum B and (+)-calanolide A, possible candidates for AIDS drugs. Further examination of the asymmetric IMA with cinchona alkaloids lacking a methoxy group on the quinoline skeleton suggested the influence of the methoxy substituent on stereoselectivity at the stereogenic centers of the chromanone systems.",10.1021/jo035753t,2004-03-12,0.5893378216174161
Organic Letters,Harnessing the Power of the Asymmetric Grignard Synthesis of Tertiary Alcohols: Ligand Development and Improved Scope Exemplified by One-Step Gossonorol Synthesis,"A series of N -substituted cyclohexyldiaminophenolic ligands for the asymmetric Grignard synthesis of tertiary alcohols is reported. The 2,5-dimethylpyrrole-decorated ligand led to improved enantioselectivities and broadened the scope of the methodology. As an exemplar, we report an unprecedented highly selective one-step synthesis of gossonorol in 93% ee, also constituting the shortest formal syntheses of natural products boivinianin B and yingzhaosu C.",10.1021/acs.orglett.0c02629,2020-10-19,0.5893375998273115
Tetrahedron,"Elenic acid, an inhibitor of Topoisomerase II, from a sponge, Plakinastrella sp.",,10.1016/0040-4039(95)00432-c,1995-04-01,0.5893354959292091
European Journal of Organic Chemistry,Modular Synthesis of Core Fucosylated N‐Glycans,"Abstract A modular synthesis of complex‐type N‐glycans containing the core fucosyl motif was optimized. The core trisaccharide building block was protected by a methoxyphenyl group for convenient core fucosylation. The trisaccharide was obtained on a large scale from the glycosylation of the corresponding chitobiosyl azide with a glucosyl donor followed by intramolecular inversion. Improved methods were established for the synthesis of the monosaccharide building blocks and for their couplings. The inversion to the β‐mannoside was accompanied by previously unnoticed side‐reactions resulting in the hydrolytic ring‐opening of the iminocarbonate intermediate. The benzylidene‐protected core trisaccharide was elongated into a biantennary N‐glycan heptasaccharide by two regio‐ and stereoselective couplings. The final fucosylation also gave some of the β anomer, which could be removed by HPLC to give an α1,6‐fucosylated N‐glycan octasaccharide.",10.1002/ejoc.201200468,2012-07-24,0.5893352743515696
Angewandte Chemie International Edition,Total Synthesis of the Antibiotic BE‐43472B,"Total control: The antibiotic BE-43472B with a unique bisanthraquinone structure has been synthesized in a completely stereocontrolled manner. The key steps are 1) a pinacol rearrangement to install the angular naphthyl group, 2) a diastereoselective methylation of a lactol derivative, and 3) the late-stage installation of the labile hydroxy group through an epoxide.",10.1002/anie.201301591,2013-05-15,0.5893341153102547
Organic Process Research & Development,A Practical Synthesis of Phenylpropargyl Aldehyde from Phenylacetylene and <i>N</i>-Formylmorpholine,A synthesis of phenylpropargyl aldehyde is described employing formylation of a phenylacetylenic Grignard reagent with N -formylmorpholine. This method afforded the product in excellent yield.,10.1021/op9900582,1999-12-01,0.5893267442800352
European Journal of Organic Chemistry,"A New Route for the Total Synthesis of 6,7‐Dihydroeponemycin","Abstract A new synthesis of dihydroeponemycin ( 2 ), a peptide epoxide with potent cytotoxic and antiangiogenesis activity, has been developed. In the initial steps, Fmoc‐Leu‐Cl was converted into the key amino ketone intermediate 9 by Stille coupling with tributylvinyltin, conjugate addition of PhSAlMe 2 to the derived enone, S ‐oxidation, and heat‐induced syn elimination. Subsequent reaction of 9 with H 2 O 2 and catalytic Triton B produced the corresponding epoxides as a 1:1 diastereomeric mixture in 89 % yield. These epoxides were separated and individually converted into 2 and(2 S )‐ epi ‐dihydroeponemycin ( 24 ) in a four‐step “one‐pot” protocol (77 % overall yield in both cases). (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2003)",10.1002/ejoc.200300401,2003-11-19,0.5893142357374744
Tetrahedron,An efficient constructive method for a tricyclic system: an important intermediate for the synthesis of tricycloclavulone,,10.1016/s0040-4039(02)02814-9,2003-02-01,0.589304565787955
Journal of the American Chemical Society,Total Synthesis of (−)-Rhazinilam:  Asymmetric C−H Bond Activation via the Use of a Chiral Auxiliary,"The antitumor agent (-)-rhazinilam was synthesized in three major steps, namely the pyrrole synthesis, selective C[bond]H bond activation, and direct macrolactam formation. The key step involved asymmetric C[bond]H bond functionalization (dehydrogenation) of the diethyl group segment in intermediate 6. This was achieved by the attachment of chiral platinum complexes to the proximal nitrogen atom. A high degree of selectivity (60-75% ee) was achieved via the use of oxazolinyl ketone chiral auxiliaries.",10.1021/ja026130k,2002-05-23,0.5892965092954887
Organic Letters,Direct Synthesis of Benzo[<i>b</i>]fluorenyl Thiophosphates via Tandem Cyclization of Diynols with (RO)<sub>2</sub>P(O)SH,"A general and metal-free protocol for the construction of benzo[ b ]fluorenyl thiophosphates was developed through the cascade cyclization of easily prepared diynols and (RO) 2 P(O)SH, with water as the only byproduct. The novel transformation involved the allenyl thiophosphate as the key intermediate, followed by Schmittel-type cyclization to achieve the desired products. Notably, (RO) 2 P(O)SH acted not only as a nucleophile but also as an acid-promoter to initiate the reaction.",10.1021/acs.orglett.3c00009,2023-02-16,0.5892872615196351
Synlett,Synthesis of Optically Active and Biologically Active Compounds,"All articles of this category Based on the consideration that biologically active chiral compounds should be prepared in optically active forms showing desired biological activities, the compounds not only exhibiting interesting biological activities but also bearing intriguing structures were selected as synthetic targets and their efficient syntheses were studied by employing optical resolution, asymmetric synthesis, and chemical transformation. Thus, efficient syntheses of anticancer agents such as anthracyclines, nogalamycins, and sesbanimides were accomplished in optically active forms. Syntheses of optically active quinocarcin and fredericamycin A showing pronounced anticancer activities were also studied. A number of efficient synthetic routes to the optically active key intermediates of carbapenem antibiotics and antihypertensive peptide-like renin inhibitors were successfully explored. 1. Introduction 2. Synthetic Studies on Optically Active Anthracyclines 2.1. Synthesis of 4-Demethoxyanthracyclinones 2.2. Synthesis of an L-Daunosamine Derivative 2.3. Synthesis of 4-Demethoxyanthracyclines 2.4. Synthesis of Anthracycline Congeners 3. Synthetic Studies on Optically Active Nogalamycin Congeners 3.1. Synthesis of the CDEF-Ring 3.2. Synthesis of Nogalamycin Congeners 3.3. Structure-Activity Relationships of Nogalamycin Congeners 4. Synthetic Studies on Optically Active Sesbanimides 4.1. Synthesis of Sesbanimide A and B 4.2. Synthesis and Structure-Activity Relationships of Sesbanimide Congeners 5. Synthetic Studies on Optically Active Quinocarcin 6. Synthetic Studies on Optically Active Fredericamycin A 7. Synthetic Studies on Optically Active Carbapenem Key Intermediates 7.1. Synthesis by the Cycloaddition Reaction of a Nitrone 7.2. Synthesis by the [2 + 2] Cycloaddition Reactions 7.3. Synthesis by the Reformatsky Reaction 8. Synthetic Studies on the Key Intermediates of Peptide-Like Renin Inhibitors 8.1. Synthesis by the 1,2-Addition Reactions with Aldehydes 8.2. Synthesis by the 1,2-Addition Reaction with an Imine 8.3. Synthesis by the [2 + 2] Cycloaddition Reaction 8.4. Synthesis Employing Optical Resolution, Asymmetric Reduction, and Chemoselective Amidation 9. Conclusion",10.1055/s-1992-21458,1992-01-01,0.5892811918152344
Organic Letters,Highly Stereoselective and Iterative Synthesis of α-(1→4)-Linked Polysaccharides Composed of 3-<i>O</i>-Methyl-<scp>d</scp>-mannose,"A second-generation synthesis of synthetic 3-O-methyl-D-mannose-containing polysaccharides (sMMPs) is reported. The glycosidation of donor B and acceptor C, prepared from a common precursor A in two and one steps, respectively, is effected by t-butyldimethylsilyl trifluoromethanesulfonate to furnish only the desired alpha-anomer D in high yields. Unlike the first-generation synthesis, this synthesis gives the desired product free from contamination of scrambling products. A three-step protocol is used to deprotect D to furnish sMMPs.",10.1021/ol0713335,2007-07-21,0.5892808488551743
Tetrahedron,Desymmetrization of α-diimines: synthesis of new 3-(diaziridin-3-yl)oxaziridines,,10.1016/j.tetlet.2013.06.090,2013-06-27,0.5892804815706212
European Journal of Organic Chemistry,Cyclobutanone Approach to the Synthesis of Cardenolides,"Abstract 17β‐(3‐Oxocyclobutyl)androstane, prepared by the thermal [2 + 2] cycloaddition of dichloroketene to 3β‐acetoxypregna‐5,20‐diene, is the key intermediate in the new, efficient synthesis of steroids bearing the 17β‐butenolide fragment that characterizes cardenolides. The six‐step synthesis of 3β‐ tert ‐butyldimethylsilyloxy‐14α‐carda‐5,20(22)‐dienolide was achieved with a total yield of 32%. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2005)",10.1002/ejoc.200400580,2005-02-01,0.5892755747876914
Journal of Organic Chemistry,A Simple and Efficient Highly Enantioselective Synthesis of α-Ionone and α-Damascone,"An efficient highly enantioselective (ee > or =99%) synthesis of alpha-ionone and alpha-damascone is described. Both enantiomers of title compounds were synthesized through two straightforward pathways diverging from enantiopure (R)- or (S)-alpha-cyclogeraniol. These versatile building blocks were obtained by regioselective ZrCl(4)-promoted biomimetic cyclization of (6S)- or (6R)-(Z)-6,7-epoxygeraniol, respectively, followed by deoxygenation of the so formed secondary alcohol. The chiral information was encoded by a highly regioselecive Sharpless asymmetric dihydroxylation of inexpensive geranyl acetate.",10.1021/jo049012j,2004-11-11,0.5892640229591243
European Journal of Organic Chemistry,Enantiodivergent Approach to Trifluoromethylated Amines: A Concise Route to Both Enantiomeric Analogues of Calcimimetic NPS R‐568,"Abstract Reported herein is a straightforward and enantiodivergent synthesis of both enantiomers of trifluoromethylated analogues of calcimimetic NPS R‐569 in a highly estereoselective manner. The synthesis features a diastereoselective synthesis of the N ‐(isopropylsulfinyl)imine unit by the “DAG methodology” and a diastereoselective addition of Ruppert–Prakash's reagent to the imine as the key steps. No protecting groups were necessary, permitting an atom economic synthesis in only six steps. Further addition reactions of the CF 3 anion to different N ‐(isopropylsulfinyl)imines were performed to demonstrate the suitability of the sulfinyl substituent to balance perfectly reactivity and diastereoselectivity.",10.1002/ejoc.200901158,2010-02-03,0.589262561227115
Organic Letters,The Stereocontrolled Total Synthesis of (−)-<i>O</i>-Methylpallidinine,"[reaction: see text] The stereocontrolled total synthesis of (-)-O-methylpallidinine, a naturally occurring Morphinan alkaloid with a B/C-trans-hydrophenanthrene framework, has been achieved starting from the chiral bicyclo[3.2.1]octenone building block by employing a single-step dihydrophenanthrene formation reaction as the key step.",10.1021/ol027040n,2002-11-14,0.5892546484137726
Journal of Organic Chemistry,Deoxygenation of Hydroquinones as a General Route to Norbornane-Fused Aromatic Systems: An Entry into Substituted and Functionalized Dimethano- and Methanoanthracenes,"A high-yielding route to substituted and functionalized dimethanoanthracenes by the Pd-catalyzed deoxyenation of the corresponding hydroquinone precursors is described. Attempts were made to deoxygenate the 9,10-dimesylate, ditosylate, and ditriflate derivatives of anti-dimethanoanthracene 1a, and it was found that under the studied conditions only the ditriflate 8a gave the corresponding deoxygenated aromatic scaffold. Optimization of the reaction conditions identified the Pd(OAc)(2)/dppf tandem as a suitable catalytic system for this transformation. The presented strategy was further extended to a novel and efficient synthetic route to methanoanthracenes employing a one-pot Pd-catalyzed deoxygenation/hydrogenation sequence.",10.1021/jo202023w,2011-12-02,0.589250615039544
Organic Process Research & Development,High-Throughput Experimentation Enabling Rapid Process Optimization of an RSV Drug Candidate,The process optimization for the synthesis of an RSV antiviral agent is described. Key to the identification of these optimal conditions was the use of high-throughput experimentation to greatly reduce the development time and realize significant process improvements in key steps such as the telescoped pyrazolopyrimidine core assembly and the borylation/Suzuki sequence.,10.1021/acs.oprd.1c00313,2021-11-02,0.5892441200924982
Angewandte Chemie International Edition,Catalytic Enantioselective Total Synthesis of Hodgkinsine B,The power of palladium: The total synthesis of the alkaloid hodgkinsine B has been achieved with just six isolated intermediates and only four chromatographic operations. The route involves a palladium-catalyzed enantioselective desymmetrizing N-allylation of meso- chimonanthine to establish the absolute configuration and elaboration of the desymmetrized core by a diastereoselective palladium-catalyzed α-oxindole arylation.,10.1002/anie.201103864,2011-08-24,0.5892381486741327
Angewandte Chemie International Edition,Total Synthesis of (−)-Bafilomycin A1: Application of Diastereoselective Crotylboration and Methyl Ketone Aldol Reactions,"A careful orchestration of protecting groups is an essential requirement for the total synthesis of the macrolide antibiotic bafilomycin A1 (1). Key steps were the Suzuki cross-coupling reaction of two advanced, suitably protected intermediates prior to closure of the macrocycle, as well as a highly stereoselective methyl ketone aldol reaction.",10.1002/(sici)1521-3773(19990601)38:11<1652::aid-anie1652>3.0.co;2-k,1999-06-01,0.5892353535192163
Tetrahedron,Enantioselective synthesis of (+)- and (−)-α-allokainic acid,,10.1016/s0040-4039(00)97768-2,1990-01-01,0.5892328326178237
Tetrahedron,Enantioselective synthesis of (−)-pinellic acid,,10.1016/j.tetlet.2007.01.163,2007-02-05,0.5892328326178237
Tetrahedron,"Enantioselective synthesis of (+)-(1R,2S)-allocoronamic acid",,10.1016/s0040-4039(00)61159-0,1992-09-01,0.5892328326178237
Tetrahedron,Enantioselective synthesis of (−)-elenolic acid and (−)-ajmalicine,,10.1016/s0040-4039(00)61950-0,1985-01-01,0.5892328326178237
Tetrahedron,Enantioselective synthesis of (−)-galantinic acid,,10.1016/j.tetlet.2004.05.151,2004-06-22,0.5892328326178237
Tetrahedron,Enantioselective synthesis of R-(+)-α and S-(−)-α-lipoic acid,,10.1016/j.tetlet.2004.06.027,2004-07-01,0.5892328326178237
European Journal of Organic Chemistry,Synthesis of New Seven-Membered Ring Cyclic Dipeptides From Functionalized β-Amino Acids,"A short synthesis of new, functionalized seven-membered ring cyclic dipeptides is described. After the coupling of N-protected β-amino acids to N-substituted α-amino tert-butyl esters, the protective groups of the terminal functions were removed and the cyclization took place diastereoselectively in the presence of the coupling agent BOP. Amide substitution was found to be effective in promoting the cyclization of linear dipeptides.",10.1002/(sici)1099-0690(200001)2000:2<251::aid-ejoc251>3.0.co;2-e,2000-01-01,0.5892325333098469
Journal of Organic Chemistry,An Expeditious Enantioselective Total Synthesis of Valilactone,"The title compound was synthesized through an expeditious route using Crimmins aldolization to establish the two key stereogenic centers and a hydroxyl group activation (HGA) protocol to construct the anti alpha,beta-disubstituted beta-lactone from the corresponding syn aldol.",10.1021/jo060844m,2006-06-28,0.5892281095805514
Tetrahedron,"Cyclofunctionalisation reactions of epoxyalcohol derivatives. 3. cyclisationacyl migration of n-benzoylcarbamates to stereodefined oxazolidinones. A new, diastereospecific route to thiamphenicol.",,10.1016/s0040-4039(00)96737-6,1987-01-01,0.58922777594226
Angewandte Chemie International Edition,"Total Synthesis, Configuration, and Biological Evaluation of Anguinomycin C","Against nuclear export! Immunofluorescence assays indicate that anguinomycin C is a potent inhibitor of protein export from the nucleus. Key features in the total synthesis of this antitumor natural product include a Cr-catalyzed enantioselective hetero-Diels–Alder reaction, a Negishi reaction with stereoinversion, and application of the DIOZ auxiliary.",10.1002/anie.200703134,2007-10-04,0.5892263528563304
Tetrahedron,The preparation of synthons on route to terpenoids of marine origin,,10.1016/s0040-4039(01)95424-3,1979-01-01,0.5892245649492476
European Journal of Organic Chemistry,Protecting‐Group‐Directed Diastereoselective Synthesis of Substituted Tetrahydropyrroloquinolines,"An efficient and protecting‐group‐directed highly diastereoselective (≥ 99:1) synthesis of tetrahydro‐3 H ‐pyrrolo[ 2,3 ‐ c ]quinolines bearing four contiguous chiral centers was achieved by using intermolecular Michael addition followed by intramolecular Mannich cyclization strategy. The domino reaction proceeded well with a broad scope of substrates under mild conditions and afforded the corresponding products in good to excellent yields. The synthetic protocol provided a straightforward synthetic route to tetrahydropyrroloquinolines as single diastereomers, which are difficult to synthesize by other methodologies.",10.1002/ejoc.202000348,2020-03-27,0.5892216297872521
Organic Letters,Total Synthesis of the Bacterial <i>ortho</i>-Quinol (+)-Strepantibin A through Iodyl-Type λ<sup>5</sup>-Iodane-Promoted Asymmetric Hydroxylative Phenol Dearomatization,"An enantioselective synthesis of the bacterial metabolite (+)-strepantibin A, a novel inhibitor of the hexokinase II (HK2) in cancer cells, is described. Its monomethylated resorcinolic para -terphenyl core was conveniently prepared through a Danheiser benzannulation. The elaboration of its ortho -quinolic chiral center was accomplished by relying on an iodyl-promoted regio- and enantioselective hydroxylative dearomatization. The olefinic side-chain of the resulting ortho -quinol was finally oxygenated under Wacker-type conditions to generate the propanone appendage of (+)-strepantibin A.",10.1021/acs.orglett.4c01653,2024-07-11,0.5892063194740277
Organic Letters,"Ruthenium-Catalyzed Synthesis of Fused Tricyclic 1<i>H</i>-2,3-Dihydropyrimido[1,2-<i>a</i>]quinolines in One Step","A novel ruthenium-catalyzed intramolecular cyclization of a nitrile and an azetidine was developed to achieve a one-step synthesis of the fused tricyclic 1H-2,3-dihydropyrimido[1,2-a]quinoline, which is the core skeleton for more than 100 natural pyoverdines and is also responsible for their fluorescence.",10.1021/acs.orglett.7b01330,2017-06-09,0.5892020108665514
Tetrahedron,"Synthesis of novel mucic acid 1,4-lactone methyl ester 3-O-ferulate related to an extractive component isolated from the peels of Citrus sudachi",,10.1016/j.tetlet.2011.11.066,2011-11-22,0.5891915963388668
Synthesis,Eine Synthese für (<i>R</i>)-(+)-Patulolid A,"All articles of this category Synthesis of ( R )-(+)-Patulolide A A new total synthesis of ( R )-(+)-patulolide A [(11 R ,2 E )-4-oxo-2-dodecen-11-olide] using the cyclization reaction of hydroxy aldehydes with ketenylidenetriphenylphosphorane is described.",10.1055/s-1993-25820,1993-01-01,0.5891837119132174
Journal of Organic Chemistry,"Syntheses of (−)-Funebrine and (−)-Funebral, Using Sequential Transesterification and Intramolecular Cycloaddition of a Chiral Nitrone","The first syntheses of (-)-funebrine [(-)-1] and (-)-funebral [(-)-2] are described. The syntheses feature sequential formation of nitrone VI from methyl glyoxylate (5) with oxime 6, transesterification of nitrone VI with (E)-crotyl alcohol (4), and intramolecular cycloaddition of the resulting nitrone VII bearing crotyl ester to afford cycloadduct 7 as a major product. The adduct 7 was readily elaborated to amino lactone (-)-3, the key synthetic intermediate of (-)-1 and (-)-2.",10.1021/jo030257q,2004-02-03,0.5891822261380544
Tetrahedron,Claisen-Ireland rearrangement: a new route to C-glycosides,,10.1016/s0040-4039(99)01055-2,1999-07-01,0.5891818192515819
Tetrahedron,Synthetic studies on bafilomycin A1: stereoselective synthesis of the C12–C17 fragment and its coupling with the C1–C11 subunit,,10.1016/j.tetlet.2004.04.034,2004-04-29,0.5891806864464778
Tetrahedron,Synthetic studies on bafilomycin A1: stereoselective synthesis of the C12?C17 fragment and its coupling with the C1?C11 subunit,,10.1016/s0040-4039(04)00807-x,2004-05-01,0.5891806864464778
Angewandte Chemie International Edition,"Enantioselective Modular Synthesis of 2,4‐Disubstituted Cyclopentenones by Iridium‐Catalyzed Allylic Alkylation","Classy combo: Together, the asymmetric iridium-catalyzed allylic alkylation and ruthenium-catalyzed ring-closing metathesis lead to an efficient synthesis of chiral cyclopentenones (see scheme). One example is the synthesis of the antitumor agent TEI-9826 with high enantiomeric purity.",10.1002/anie.200503945,2006-03-09,0.589176055507917
Synlett,An Enantioselective Formal Total Synthesis of Phytuberin,All articles of this category A formal total synthesis of phytuberin was achieved in eight steps from carvone. The key transformations were the alkoxide-directed addition of dichloromethyl lithium and the alkoxide-mediated hydrolysis of the dichloromethyl carbinol. dichloromethyl lithium - dichloromethyl carbinol,10.1055/s-1999-2860,1999-09-01,0.589175181779891
Organic Letters,Total Synthesis of (±)-Sorocenol B Employing Nanoparticle Catalysis,The total synthesis of (±)-sorocenol B has been accomplished featuring key steps including silver nanoparticle (AgNP)-catalyzed Diels-Alder cycloaddition and late-stage Pd(II)-catalyzed oxidative cyclization. The synthetic natural product exhibited low micromolar cytotoxic activity against a number of human cancer cell lines.,10.1021/ol300800r,2012-05-03,0.589171346784822
Organic Letters,Total Syntheses of Uncommon C<sub>30</sub> Terpenoids: Chamaecydin and Isochamaecydin,"terpenoids comprising abietane-type diterpenes and thujane-type monoterpenes, were achieved from β-pinene with (-)-sabinene in 18 and 20 steps, respectively. Key steps include a Claisen-Ireland rearrangement to establish the all-carbon quaternary center, a Rh catalyzed C-H bond insertion reaction to install a spiro-five-membered ring and a Lewis acid promoted cyclization of polyenes to construct the two six-membered rings.",10.1021/acs.orglett.3c02483,2023-10-20,0.5891711399720129
Journal of Organic Chemistry,"Highly Efficient Formal Synthesis of Cephalotaxine, Using the Stevens Rearrangement−Acid Lactonization Sequence as A Key Transformation","Cephalotaxine (1), the major alkaloid isolated from Cephalotaxus species, has attracted considerable attention due to the promising antitumor activity of several of its derivatives and its unique structural features. Herein we describe a highly efficient formal synthesis of 1 employing the [2,3]-Stevens rearrangement-acid lactonization sequence as a key transformation from readily available (3,4-dimethoxyphenyl)acetic acid, methyl prolinate, and allyl bromide.",10.1021/jo8025252,2009-01-26,0.5891709129939469
Organic Letters,"Enantioselective, Protecting-Group-Free Total Synthesis of Boscartin F","In this work, the protecting-group-free total synthesis and stereochemical assignment of (−)-boscartin F have been reported. The key steps, including Sharpless asymmetric epoxidation, I 2 -mediated iodoetherification, aldol reaction, and ring-closing metathesis, allowed for rapid and highly stereoselective access to boscartin F. In addition, single-crystal X-ray crystallographic analysis of the semicarbazone derivative 22 confirmed the stereochemistry of boscartin F.",10.1021/acs.orglett.7b03979,2018-01-23,0.5891680908044359
Tetrahedron,Development of one-pot synthesis of α-hydroxy α-trifluoromethyl amides,,10.1016/j.tetlet.2013.07.064,2013-07-18,0.5891629744094891
Journal of Organic Chemistry,"Efficient Routes to Pyrazolo[3,4-<i>b</i>]indoles and Pyrazolo[1,5-<i>a</i>]benzimidazoles via Palladium- and Copper-Catalyzed Intramolecular C−C and C−N Bond Formation","Efficient synthetic routes to pyrazolo[3,4-b]indoles and pyrazolo[1,5-a]benzimidazoles via intramolecular palladium- and copper-catalyzed cyclization of 1-aryl/1-unsubstituted 5-(2-bromoanilino)pyrazole precursors via intramolecular C-C and C-N bond formation have been reported.",10.1021/jo901309t,2009-08-11,0.5891557680197722
Organic Process Research & Development,Efficient Synthesis of Crisaborole from <i>m</i>-Cresol: A Practical and Scalable Process,"Herein, process improvement work on the phosphodiesterase-4 inhibitor crisaborole is described. The starting material 2-bromo-5-hydroxybenzaldehyde was replaced with the low-cost m -cresol. The process involves the purification of the low-melting-point bromophenol by a cocrystal strategy, selective debromination of the gem -dibromide byproduct, boronation through a telescoped process, and design of experiments optimization in the active pharmaceutical ingredient (API) synthesis stage. The economic, efficient, and practical synthesis of crisaborole was successfully achieved. It is worth noting that filtration unit operations were applied in the scale-up process of Miyaura borylation to address the common issue of incomplete conversion in this process.",10.1021/acs.oprd.5c00075,2025-05-02,0.5891441477466952
Synthesis,"First Stereoselective Synthesis of Diethyl cis- and trans-(4-Hydroxy-1,2,3,4-tetrahydroquinolin-2-yl)phosphonates and Ethyl Phenylphosphinates from Quinolin-4(1H)-one","Abstract We report a practical method for the first stereoselective synthesis of diethyl cis- and trans-(4-hydroxy-1,2,3,4-tetrahydroquinolin-2-yl)phosphonates, as well as ethyl cis- and trans-(4-hydroxy-1,2,3,4-tetrahydroquinolin-2-yl)phenylphosphinates. The main feature of this method is the regioselective 1,4-phosponylation to N-Cbz quinolin-4(1H)-one using diethyl phosphite or ethyl phenylphosphinate followed by a highly diastereoselective reduction to give the cis stereoisomers as favored products, which were converted into trans stereoisomers through the Mitsunobu reaction. Cleavage of the N-Cbz bond under hydrogenolysis gave the target heterocyclic α-aminophosphonates and α-aminophosphinates.",10.1055/a-2164-2075,2023-08-31,0.5891427642075145
Journal of Organic Chemistry,Scalable DOS-like Strategy to the δ-Amino Acids via Petasis/Cross Metathesis Reactions Sequence,"A convenient and scalable approach to δ,δ-spirosubstituted δ-amino acids and their α,β-unsaturated analogues from bulk ketones was elaborated. The proposed routes include Petasis reaction of starting ketone with allylboronic acid pinacol ester and methanolic ammonia, and cross metathesis with acrylic acid derivatives as key steps. The developed protocols are novel, robust, and economically efficient. They avoid tedious separation and purification, can be scaled up to 40 g of final compounds and propose an efficient way to novel conformationally rigid foldamers.",10.1021/acs.joc.5c00620,2025-07-03,0.5891401897785106
Organic Letters,Novel Efficient Routes to Heparin Monosaccharides and Disaccharides Achieved via Regio- and Stereoselective Glycosidation,A new methodology for the synthesis of heparin building blocks has been developed. We describe novel efficient routes to both L-iduronic acid and D-glucuronic acid acceptors. Glycosylation with thioglycosides donors gave corresponding disaccharides in a regio- and stereoselective fashion. An improved approach to synthesizing azido-glucose thioglycoside donor to render azido-sugar from mannose via nucleophilic substitution is described. [reaction: see text],10.1021/ol036390m,2004-02-11,0.5891396289744821
Synlett,New Routes Toward Drimanes and<i>nor</i>-Drimanes from (-)-Sclareol,"All articles of this category New synthetic strategies to prepare natural drimanes and monocarbocyclic terpenoids from (-)-sclareol ( 2 ) are reported. The preparation of natural 9,11-drimen-8α-ol ( 12 ) and the first enantiospecific synthesis of marine metabolite fulvanin 2 ( 1 ) are described. terpenoids - marine metabolites - decarboxylation - isocyanates",10.1055/s-2000-7924,2000-01-01,0.589138471352758
Organic Letters,Bioinspired Synthesis of Microstegiol and Biosynthetically Related Skeleton-Rearranged Abietanes,"We report a bioinspired synthesis of microstegiol and biosynthetically related skeleton-rearranged abietane diterpenoids from commercially available carnosic acid. The strategy features a Wagner-Meerwein type methyl migration followed by several cascade transformations, enabling the divergent synthesis of five abietane diterpenoids, including viridoquinone, prattinin A, saprorthoquinone, microstegiol, and 1-deoxyviroxocin.",10.1021/acs.orglett.5c00033,2025-02-28,0.5891355665502219
Tetrahedron,A novel synthesis of coumarins employing triphenyl(α-carboxymethylene)phosphorane imidazolide as a C-2 synthon,,10.1016/j.tetlet.2008.10.133,2008-11-01,0.5891323536942191
Angewandte Chemie International Edition,Total Synthesis of Rhizopodin,"Symmetry helps: The total synthesis of the potent actin-targeting C2-symmetric myxobacterial macrolide rhizopodin (see scheme) is accomplished by the convergent assembly of three building blocks of similar complexity, a concise macrocyclization strategy, and a late-stage introduction of the labile side chains.",10.1002/anie.201201946,2012-04-24,0.5891307550315901
European Journal of Organic Chemistry,"Synthesis and Characterization ofall-E-(4,4′-13C2)-Astaxanthin Strategies for Labelling the C15-End Groups of Carotenoids","The all-E isomer of (4,4′-13C2)astaxanthin (1a) has been prepared by total synthesis starting from commercially available 99% 13C enriched acetonitrile. The labelled astaxanthin was obtained in high purity and with high isotope incorporation. For this synthesis, the C15 + C10 + C15 strategy was used. The central C10-synthon, 2,7-dimethylocta-2,4,6-triene-1,8-dial (3), was coupled with 13C-enriched C15-phosphonium salt 2a. The new synthetic scheme for the preparation of the C15-phosphonium salt is discussed in this paper; the same scheme can be used to label all positions and combinations of positions of the C15-phosphonium salt.",10.1002/(sici)1099-0690(200003)2000:5<829::aid-ejoc829>3.0.co;2-z,2000-03-01,0.5891271118807316
Tetrahedron,A new heteroditopic receptor and sensor highly selective for bromide in the presence of a bound cation,,10.1016/j.tetlet.2005.02.156,2005-03-15,0.5891256656656597
European Journal of Organic Chemistry,Enantioselective Pictet–Spengler Condensation to Access the Total Synthesis of (+)‐Tabertinggine,"Abstract A chiral phosphoric acid (CPA)‐catalyzed enantioselective Pictet–Spengler condensation/lactamization cascade reaction was established, which paved the way of the collective synthesis of iboga‐type indole alkaloids. Herein, we presented the asymmetric total synthesis of iboga‐type indole alkaloid (+)‐tabertinggine.",10.1002/ejoc.202200088,2022-03-08,0.5891204895659575
Tetrahedron,"Synthesis and asymmetric hydrogenation of 3,5-dioxoheptanedioates. Preparation of enantiomerically pure substituted δ-valerolactones",,10.1016/s0040-4039(00)00747-4,2000-06-01,0.5891190343905309
European Journal of Organic Chemistry,"First Asymmetric Synthesis of (+)‐Sordidin and (–)‐7‐<i>epi</i>‐Sordidin, Aggregation Pheromones of the Banana Weevil <i>Cosmopolites sordidus</i>","Abstract The asymmetric synthesis of (1 S ,3 R ,5 R ,7 S )‐(+)‐sordidin and 7‐ epi ‐(1 S ,3 R ,5 R ,7 R )‐(–)‐sordidin, both components of the natural male‐produced aggregation pheromone of the banana weevil Cosmopolites sordidus (Germar), starting from 2,2‐dimethyl‐1,3‐dioxan‐5‐one is described. Two of the stereogenic centers were generated by three α‐alkylations of the corresponding RAMP‐hydrazone. Diastereoselective epoxide opening as another key step of the synthesis employing the aza‐enolate of 3‐pentanone SAEP‐hydrazone as nucleophile and subsequent acidic intramolecular acetalisation furnished the sordidin C‐7 epimers in good overall yield (39 %) as a 1.5:1 diastereomeric mixture. The epimers could be separated by preparative GC and thus, each of them could be obtained in high diastereomeric and enantiomeric purity ( de ≥ 97 %, ee ≥ 98 %). (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2005)",10.1002/ejoc.200500112,2005-05-07,0.5891168178728432
Tetrahedron,Studies toward the total synthesis of (+)-gelsemine and synthesis of spirocyclopentaneoxindole through intramolecular Michael cyclization,,10.1016/j.tetlet.2012.08.048,2012-08-16,0.5891116107037202
Synthesis,Enantioselective Synthesis of 2-Substituted Pyrrolidines via Intramolecular Reductive Amination,"Catalyzed by the complex generated in situ from iridium and the chiral ferrocene ligand, tert-butyl (4-oxo-4-arylbutyl)carbamate substrates were deprotected and then reductively cyclised to form 2-substituted arylpyrrolidines in a one-pot manner, in which the intramolecular reductive amination was the key step. A range of chiral 2-substituted arylpyrrolidines were synthesised in up to 98% yield and 92% ee.",10.1055/s-0037-1611533,2019-05-07,0.5891110746905124
Tetrahedron,Enantioselective synthesis of the tricyclic core of (−)-FR901483,,10.1016/j.tetlet.2007.01.171,2007-02-05,0.5891060239278316
Angewandte Chemie International Edition,Yttrate-Mediated Ligand Transfer and Direct Synthesis as a Route to Amidopalladium Complexes,"A ligand transfer from yttrium to palladium and the regeneration of 1 are the crucial steps in the efficient synthesis of the very strained amidopallium complex 2 from [(cod)PdCl2] and 1 (cod=cyclooctadiene). In the light of the numerous “ate” complexes of early transition metals, this synthetic route should have enormous potential.",10.1002/(sici)1521-3773(19980403)37:6<832::aid-anie832>3.0.co;2-a,1998-04-03,0.589105505322124
European Journal of Organic Chemistry,Total Synthesis of Ectocarpin A,"A total enantioselective synthesis of ectocarpin A, an oxylipin identified through the first hydroperoxide bicyclase activity of CYP5164A3 in brown algae, has been successfully completed in 12 steps starting from tetrahydro‐1H‐cyclopentafuranone. Key transformations include the creation of the chiral tetrahydro‐1H‐cyclopentafuranone, a diastereoselective epoxidation, an enzymatic desymmetrization of a 1,4‐diol, an epimerization, and both Wittig and Julia‐Kocienski olefinations to build the carbon framework of ectocarpin A.",10.1002/ejoc.202500381,2025-04-14,0.589103456294748
Organic Letters,Stereoselectivity in <i>N</i>-Iminium Ion Cyclization: Development of an Efficient Synthesis of (±)-Cephalotaxine,A stereoselective N-iminium ion cyclization with allylsilane to construct vicinal quaternary-tertiary carbon centers was developed for the concise synthesis of (±)-cephalotaxine. The current strategy features a TiCl4-promoted cyclization and ring-closure metathesis to furnish the spiro-ring system. The stereochemical outcome in the N-acyliminium ion cyclization was rationalized by the stereoelectronic effect of the Z- or E-allylsilane. Two diastereomers arising from the cyclization were merged into the formal synthesis of (±)-cephalotaxine.,10.1021/acs.orglett.5b02106,2015-09-02,0.5890930159822452
Tetrahedron,"Synthesis of (±)-E-(1,2,4-trihydroxy-2,6,6-tirmethylcyclohexyl)-but-3-en-2-one: A novel degraded carotenoid isolated from New Zealand thyme (thymus vulgaris) honey",,10.1016/s0040-4039(00)79850-9,1992-05-01,0.589091091546237
Tetrahedron,An improved version of the Sharpless asymmetric dihydroxylation,,10.1016/s0040-4039(00)01396-4,2000-10-01,0.589085650309003
Organic Letters,"Synthesis of a Functionalized 7,6-Bicyclic Spiroimine Ring Fragment of the Spirolides","The asymmetric synthesis of a functionalized 7,6-spiroimine related to the spirolides is described. Intermolecular Diels-Alder cycloaddition of a chiral trisubstituted dienophile and Danishefsky's diene enabled simultaneous installation of the C7 and C29 stereocenters. Further transformations and late-stage aza-Wittig cyclization afforded the spiroimine in good yield. During this study, an unprecedented 14-membered dialdimine was also obtained.",10.1021/ol102525w,2010-10-28,0.5890855469971698
Organic Letters,Total Synthesis of the Anti-Apoptotic Agents Iso- and Bongkrekic Acids,The first convergent total synthesis of isobongkrekic acid is reported involving three different stereospecific palladium cross-couplings for the formation of the diene units. Access to bongkrekic acid by this route is also demonstrated. These syntheses involve the formation of several potentially general building blocks.,10.1021/ol902676t,2009-12-16,0.5890696096099303
Organic Letters,Total Synthesis of (+)-Antroquinonol and (+)-Antroquinonol D,"The first total synthesis of (+)-antroquinonol and (+)-antroquinonol D, two structurally unique quinonols with a sesquiterpene side chain, is described. The route features an iridium-catalyzed olefin isomerization-Claisen rearrangement reaction (ICR), lactonization, and Grubbs olefin metathesis. The requisite α,β-unsaturation was achieved via the selenylation/oxidation protocol and elimination of β-methoxy group to provide two natural products from a common intermediate.",10.1021/acs.orglett.5b00046,2015-02-13,0.5890524627159329
European Journal of Organic Chemistry,"Preparation of New 1,4‐Diazocanes as Scaffolds for Combinatorial Chemistry","Abstract Hexahydro‐2‐oxo‐1,4‐diazocin‐6‐carboxylic acid constitutes a conformationally rigid, crown‐shaped scaffold. An orthogonally protected (Boc at N‐4 and methyl ester at 6‐CO 2 H) representative was prepared by ring expansion of a 3‐pyrrolidone‐derived 1,4‐diketone with MeNH 2 . After deprotection, this building block was further diversified by reductive aminations and amidations and by sulfonamide and urea formation. Furthermore, the 6‐CO 2 H function was transformed into a 6‐NHCbz group in one step by carboxamide degradation in the presence of BnOH. An example of a cyclic tripeptoidic structure was synthesized by amidation with N ‐Boc‐β‐alanine and glycine methyl ester. Structural features of the eight‐membered heterocycle were established by single‐crystal X‐ray structure analysis of a 4‐bromoaniline derivative.",10.1002/ejoc.201101645,2012-02-03,0.5890425113068916
Journal of Organic Chemistry,Total Synthesis of (±)-Antroquinonol D,"Total synthesis of (±)-antroquinonol D, which is isolated from very expensive and rarely found Antrodia camphorata and which has potential anticancer properties, was achieved from 4-methoxyphenol. In addition, a Michael addition to dimethoxy cyclohexadienones was studied. The main step involved chelation and substrate-controlled diastereoselective reduction of cyclohexenone and lactonization. Lactone synthesis facilitated the diastereoselective reduction of ketone, which help control the desired stereochemistry at the crucial stereogenic center in the natural product. Other key reactions in the synthesis involved a Michael addition of dimethyl malonate on cyclohexadienone, dihydroxylation, and Wittig olefination. A sesquiterpene side chain was synthesized through coupling with geranyl phenyl sulfide and Bouveault-Blanc reduction.",10.1021/jo501735z,2014-11-06,0.5890420394756793
Journal of Organic Chemistry,Synthesis of Modified Methyl Furanosides by Intramolecular Oxa-Michael Reaction followed by Pummerer Rearrangement,"A new method is described for the synthesis of ribofuranoses modified at the C3 and C5 positions. The key step is an intramolecular oxa-Michael reaction on a vinyl sulfoxide to install the C2 hydroxy group. The methyl furanosides are obtained by Pummerer rearrangement of the sulfoxide into the corresponding aldehyde, acidic deprotection of the benzylidene acetal, and cyclization.",10.1021/jo100241e,2010-04-12,0.5890405709504213
Journal of Organic Chemistry,"Toward Pyrrolo[2,3-<i>d</i>]pyrimidine Scaffolds","Herein, we present a new route to highly substituted pyrrolo[2,3-d]pyrimidines featuring a Ugi-Smiles/Sonogashira cascade followed by an efficient base-catalyzed intramolecular cyclization. When formaldehyde is chosen as input in the Ugi-Smiles step, aromatic fused systems are eventually obtained through the isomerization of an exo-alkylidene intermediate.",10.1021/jo100759b,2010-07-01,0.5890392737661422
Tetrahedron,"The first stereo selective total synthesis of (3R),(5R)-5-hydroxy-de-O-methyllasiodiplodin and its epimer via an RCM protocol",,10.1016/j.tetlet.2010.05.115,2010-06-02,0.5890347584588119
Tetrahedron,Ring opening of benzoxazinones: An improved and efficient synthesis of clavatustides A &amp; B,,10.1016/j.tetlet.2017.07.059,2017-07-17,0.5890335857561304
Organic Letters,Total Synthesis and Biological Evaluation of the Potent HIV Latency-Reversing Agent Ansellone A and its Analogues,"The total synthesis and biological evaluation of the marine sesterterpenoid ansellone A ( 1 ), an HIV latency-reversing agent, and its analogues are reported. The key to the success of this synthetic route is a Prins cyclization reaction enabled by the strategic use of the TfO group for stabilization of the acid-labile tertiary allylic alcohol. The SAR study found the alcohol analogue to exhibit more potent activity than 1 .",10.1021/acs.orglett.1c00151,2021-02-11,0.5890326086708718
Synthesis,Asymmetric Total Syntheses of (<i>R</i>)-(-)-Argentilactone and (<i>S</i>)-5-Hexadecanolide,The simple and efficient asymmetric syntheses of (R)-(-)-argentilactone and (S)-5-hexadecanolide were achieved from the same starting material by a similar strategy. The key intermediates for both molecules were chiral 5-hydroxyalk-2-en-6-ynoates.,10.1055/s-2006-942518,2006-08-25,0.589031000329895
Journal of Organic Chemistry,Formal Total Synthesis of Cyanolide A,"Formal total synthesis of cyanolide A, aglycosidic dimeric macrolide is accomplished. The key reactions involved are asymmetric acetate aldol reaction, CBS reduction, and Shiina's lactonization.",10.1021/jo102401v,2011-01-31,0.589027456585813
Tetrahedron,"An improved procedure for aldehyde-to-alkyne homologation via 1,1-dibromoalkenes; synthesis of 1-bromoalkynes",,10.1016/s0040-4039(00)73227-8,1994-05-01,0.5890264842626409
Tetrahedron,Diastereoselective organocatalytic Mannich access to azacyclic system en route to lyconadin A,,10.1016/j.tetlet.2014.07.079,2014-07-26,0.5890206715524424
Organic Letters,Asymmetric Total Synthesis of Distaminolyne A and Revision of Its Absolute Configuration,"The first total synthesis of a marine derived polyacetylene, distaminolyne A, and its enantiomer were achieved from the commercially available undec-10-en-1-ol. A key proline-catalyzed asymmetric α-aminooxylation of an aldehyde intermediate was used to introduce the chiral center en route to the enantiomerically pure 1,2-amino alcohols. The absolute configuration of both synthesized enantiomers of distaminolyne A was confirmed by using chiral derivatizing agents, leading to revision of the natural product absolute configuration from 2S to 2R. Antibacterial, pancreatic lipase (PL) inhibitory, and protein-tyrosine phosphatase 1B (PTP1B) inhibitory activities were evaluated.",10.1021/acs.orglett.6b03892,2017-01-23,0.5890191861186144
Organic Letters,Asymmetric Total Synthesis of (+)-Danicalipin A,"A convergent asymmetric total synthesis of (+)-danicalipin A is accomplished, in which two chlorinated fragments are stereoselectively joined by 1,3-dipolar coupling, leading to the confirmation of the absolute configuration of the natural product.",10.1021/ol1029518,2011-02-02,0.5890173530338536
Tetrahedron,An efficient synthesis of chiral amino acid and peptide alkylamides via CLEC-subtilisin catalyzed coupling and in situ resolution,,10.1016/0040-4039(96)01119-7,1996-07-01,0.5890165735776614
Journal of Organic Chemistry,"One-Pot Synthesis of 2,4,5-Trisubstituted Imidazoles via [2 + 2 + 1] Cycloannulation of 1,3-Bishet(aryl)-monothio-1,3-diketones, α-Substituted Methylamines and Sodium Nitrite through α-Nitrosation of Enaminones","An efficient one-pot synthesis of a series of diversely functionalized trisubstituted 4(5)het(aroyl)-2,5(4)-het(aryl)/alkylimidazoles from readily available 1,3-bishet(aryl)monothio-1,3-diketones has been reported. This novel sequential one-pot, three step protocol, wherein three new carbon nitrogen bonds are formed in contiguous fashion, involves in situ generation of enaminones by reaction of monothio-1,3-diketones with α-substituted methylamines, followed by their α-nitrosation with sodium nitrite and subsequent base mediated intramolecular heterocyclization of the resulting α-hydroxyiminoimines to trisubstituted imidazoles in high yields under mild conditions. These newly prepared 4(5)-het(aroyl)-5(4)-het(aryl)/alkylimidazoles are shown to exist as tautomeric mixture, however, their subsequent alkylation with methyl iodide in the presence of potassium carbonate affords 1-N-methy-2,5-bishet(aryl)-4-het(aroyl)imidazoles in highly regioselective fashion in most of the cases. Synthesis of few 4(5)-(2-hydroxyphenyl)-2,5(4)-substituted imidazoles, which are known to be good coordinating ligands, has also been reported. A probable mechanism for the formation of these imidazoles from hydroxyiminoimine intermediates has also been suggested.",10.1021/acs.joc.6b00938,2016-05-19,0.5890129467564785
Organic Letters,Asymmetric CuH-Catalyzed Hydrosilylations en Route to the C-9 Epimer of Amphidinoketide Ι,"The C-9 diastereomer of amphidinoketide I has been synthesized. An asymmetric CuH-catalyzed hydrosilylation based on the Solvias nonracemic Josiphos-related ligand (R,S)-PPF-P(t-Bu)2 was successfully used to introduce each of three stereocenters found in the target compound.",10.1021/ol701999h,2007-10-19,0.5890093491920482
Synthesis,"Enantioselective Synthesis of Differently Protected 1,2-Diamines via α-Alkylation of Dibenzylaminoacetaldehyde SAMP-Hydrazone","All articles of this category Chiral, unsymmetrically and differently protected 1,2-diamines 4 were prepared in moderate to good overall yields and with high asymmetric inductions (ee = 91-99%) by α -alkylation of N,N -dibenzylaminoacetaldehyde SAMP-hydrazone ( S )- 2 with subsequent oxidative cleavage to the corresponding α -aminonitriles, reduction to the diamines, and protection of the latter. asymmetric synthesis - 1,2-diamines - SAMP-hydrazones - α -alkylation - hydrazone/nitrile conversion",10.1055/s-1996-4166,1996-01-01,0.5890072171292696
European Journal of Organic Chemistry,"Synthesis of Natural Rubrolides B, I, K, L, M, O and Analogues","Abstract The chlorinated natural products, rubrolides B, I, K, L, M and O and analogues were synthesized in only five steps employing a robust and divergent synthetic strategy. The synthesis is performed without using protecting groups starting from a key intermediate, which can be synthesized from commercially available tetronic acid in only two steps. Selective halogenation and vinylogous aldol condensation enable the efficient synthesis of highly halogenated natural occurring rubrolides as well as synthetic analogues to build up a compound library for antiviral and antibiofilm testing. All synthesized compounds were then tested for their activity against the two influenza A virus strains p H1N1 and H3N2 as well as for their antibiofilm activity. Naturally occurring as well as synthetic analogues showed promising antiviral and antibiofilm activities.",10.1002/ejoc.202100526,2021-07-12,0.5890062235780115
Journal of Organic Chemistry,Pd-Catalyzed Tandem Reaction of 2-Aminostyryl Nitriles with Arylboronic Acids: Synthesis of 2-Arylquinolines,"A novel palladium-catalyzed protocol for the synthesis of 2-arylquinolines via tandem reaction of 2-aminostyryl nitriles with arylboronic acids has been developed with good functional group tolerance. The presented approach offers a new synthetic pathway toward the core structures of 2-arylquinolines compared to classical condensation reaction of ( E )-2-aminostyryl aryl ketones. Moreover, the present synthetic route could be readily scaled up to gram quantity without difficulty. Preliminary mechanistic experiments showed that this transformation involves a nucleophilic addition of aryl palladium species to the nitrile to generate an aryl ketone intermediate followed by an intramolecular cyclization and dehydration to quinoline ring.",10.1021/acs.joc.9b01875,2019-09-24,0.5890059448789953
Journal of Organic Chemistry,Exploitation of a Multienzymatic Stereoselective Cascade Process in the Synthesis of 2-Methyl-3-Substituted Tetrahydrofuran Precursors,"Enantiopure 2-methyl-3-substituted tetrahydrofurans are key precursors of several biologically active products (drugs, flavors, and agrochemicals). Thus, a stereocontrolled and efficient methodology for the obtainment of these synthons is highly desirable. We exploited a two-step multienzymatic stereoselective cascade reduction of α-bromo-α,β-unsaturated ketones to give the corresponding bromohydrins in good yields, with high ee and de values. The cascade process is catalyzed by an ene-reductase and an alcohol dehydrogenase. Further manipulations of these bromohydrins, by two diastereodivergent routes, allowed the preparation of the tetrahydrofuran synthons. One route is based on a lipase catalyzed cleavage of the protecting group. The second route is characterized by a camphor sulfonic acid mediated isomerization of a β-hydroxyepoxide to give the tetrahydrofuran-2-ol. Finally, the synthesis of the most odorous and pleasant stereoisomer of the roasted meat aroma, i.e., (2S,3R)-2-methyl-3-thioacetate tetrahydrofuran, is reported as well.",10.1021/acs.joc.6b02927,2017-01-17,0.5890033036835991
Tetrahedron,Synthesis of spirolactams and spiropiperidines as CCR4 receptor antagonists,,10.1016/j.tetlet.2005.10.139,2005-11-15,0.5890025979606073
Journal of Organic Chemistry,"Ring-Closing Metathesis-Based Synthesis of (3<i>R</i>,4<i>R</i>,5<i>S</i>)-4-Acetylamino-5-amino-3-hydroxy- cyclohex-1-ene-carboxylic Acid Ethyl Ester:  A Functionalized Cycloalkene Skeleton of GS4104","(3R,4R,5S)-4-Acetylamino-5-amino-3-hydroxy-cyclohex-1-ene-carboxylic acid ethyl ester, a functionalized cyclohexene skeleton of GS4104, was diastereoselectively synthesized. A major advantage of this synthesis is the use of readily available L-serine to replace frequently used (-)-shikimic acid or (-)-quinic acid as the starting material. Ring-closing metathesis and diastereoselective Grignard reactions successfully served as the key steps. Absolute configurations of the key intermediates were confirmed by corresponding two-dimensional NMR studies.",10.1021/jo060633h,2006-06-06,0.5890022048601858
Journal of Organic Chemistry,Application of the Dakin−West Reaction for the Synthesis of Oxazole-Containing Dual PPARα/γ Agonists,An improved method for the preparation of a series of oxazole-containing dual PPARalpha/gamma agonists is described. A synthetic sequence utilizing a Dakin-West reaction was devised that allows for the introduction of the oxazole ring either late in the synthetic sequence via aminomalonate-derived chemistry or in pivotal SAR intermediates derived from aspartic acid.,10.1021/jo026655v,2003-03-06,0.5889956689176828
Tetrahedron,RNA synthesis via dimer and trimer phosphoramidite block coupling,,10.1016/j.tetlet.2011.03.042,2011-03-16,0.588992541315601
Journal of Organic Chemistry,Total Synthesis of (−)-Muraymycin D2 and Its Epimer,"Full details of the first total synthesis of (-)-muraymycin (MRY) D2 and its epimer, the antibacterial nucleoside natural product, are described. Key strategic elements of the approach include the preparation of the urea dipeptide moiety found in the muraymycins containing an L-epi-capreomycidine via a nitrene C-H insertion of the sulfamate 10 and the fully protected muraymycin skeleton at a late stage by an Ugi four-component reaction. Thus, the nitrene C-H insertion of the sulfamate 10 with 10 mol % of Rh(2)(esp)(2) catalyst gave the cyclic sulfamates 11a and 11b in 47% yield (11a:11b = 1:2.0). Construction of the cyclic guanidine skeleton was effected through the HgBr(2)-promoted cyclization of 42 followed by desulfonylation upon acetolysis of the oxathiazinane ring to give 43 in good yield. The amine obtained by selective removal of the Cbz group of the alcohol 44 was reacted with MeSC(=O)-L-Val-O-t-Bu (38) to provide 45, which was oxidized to the carboxylic acid 46. Reaction of 46, isonitrile 51, isovaleraldehyde, and 2,4-dimethoxybenzylamine furnished the desired Ugi products, the final deprotection of which successfully afforded (-)-MRY D2 and epi-MRY D2 (53) after HPLC separation of the diastereomers. This approach would afford ready access to a range of analogues simply by altering each component.",10.1021/jo9027193,2010-02-09,0.588991109032049
Tetrahedron,Synthesis of sesquiterpene antitumor lactone I a new synthesis of the cis-fused δ-valerolactone AB ring model in vernolepin and vernomenin,,10.1016/s0040-4039(01)86109-8,1979-01-01,0.5889908936245131
Journal of Organic Chemistry,Silyl Enol Ether Prins Cyclization: Diastereoselective Formation of Substituted Tetrahydropyran-4-ones,"A diastereoselective synthesis of cis-2,6-disubstituted tetrahydropyran-4-ones was developed. The key step of this methodology, a silyl enol ether Prins cyclization, was promoted by a condensation reaction between a hydroxy silyl enol ether and an aldehyde to afford substituted tetrahydropyran-4-ones. The cyclization was tolerant of many functional groups, and the modular synthesis of the hydroxy silyl enol ether allowed for the formation of more than 30 new tetrahydropyran-4-ones with up to 97% yield and >95:5 dr. The cyclization step forms new carbon-carbon and carbon-oxygen bonds, as well as a quaternary center with good diastereoselectivity. The method provides a versatile route for the synthesis of substituted tetrahydropyrans.",10.1021/jo501580p,2014-09-09,0.5889892288641272
Organic Letters,Modular Approach to <i>pseudo</i>-Neoclerodanes as Designer κ-Opioid Ligands,"Informed by previous semisynthetic work on salvinorin A, a modular total synthesis has been developed capable of producing novel compounds targeting the κ-opioid receptor. The strategy has permitted the deliberate simplification and introduction of functionality about the target molecule to provide access to molecular features on salvinorin A otherwise unattainable by semisynthesis. Using this approach, a potent pseudo-neoclerodane κ-opioid receptor ligand (2) has been realized.",10.1021/acs.orglett.7b02684,2017-09-14,0.5889882229657913
Journal of Organic Chemistry,<i>De Novo</i> Asymmetric Synthesis of a 6-<i>O</i>-Methyl-<scp>d</scp>-<i>glycero</i>-<scp>l</scp>-<i>gluco</i>-heptopyranose-Derived Thioglycoside for the Preparation of <i>Campylobacter jejuni</i> NCTC11168 Capsular Polysaccharide Fragments,"An enantioselective de novo synthesis of a thioglycoside derivative of the 6-O-methyl-D-glycero-L-gluco-heptopyranose residue found in the Campylobacter jejuni NCTC11168 (HS:2) capsular polysaccharide is reported. The compound is obtained from a furfural-derived chiral diol in 11 steps. Notably, compared to the only previous synthesis of this molecule, this approach significantly reduces the number of purification steps required to obtain the target.",10.1021/acs.joc.6b00296,2016-03-16,0.5889871444179267
Journal of Organic Chemistry,A Stereodivergent Strategy for Total Syntheses of Antirhine Alkaloids,"Total syntheses of the antirhine alkaloids are described. The cyanide-catalyzed imino-Stetter reaction of the aldimine derived from ethyl 2-aminocinnamate and 4-bromopyridine-2-carboxaldehyde provided a 2-pyridinyl substituted indole-3-acetate, which was further converted into the corresponding indoloquinolizidinium intermediate through C-ring formation. Subsequent trans -selective installation of the homoallylic alcohol side-chain at C-15 in the resulting indoloquinolizidinium allowed the total syntheses of antirhine and its known epimer.",10.1021/acs.joc.0c02936,2021-03-01,0.5889812631591166
European Journal of Organic Chemistry,A Divergent and Stereoselective Approach for the Syntheses of Some Polyhydroxylated Indolizidine and Pyrrolizidine Iminosugars,"Abstract A common, divergent, and efficient approach to the syntheses of (+)‐steviamine ( 9 ), (–)‐1‐deoxy‐8a‐ epi ‐castanospermine ( 10 ), (+)‐trihydroxyindolizidine ( 11 ), (+)‐3,7a‐di‐ epi ‐hyacinthacine A1 ( 12 ), and (–)‐2‐ epi ‐lentiginosine ( 4 ) was achieved by starting from D ‐ribose‐derived intermediate 13 . The key steps involved in these syntheses are a highly diasteroselective Grignard addition to a ribosylimine, a one‐pot stereoselective intramolecular reductive amination, a selectve deprotection of a silyl ether, and a ring‐closing metathesis (RCM) reaction.",10.1002/ejoc.201201342,2013-02-11,0.5889811768893763
Journal of Organic Chemistry,General Approach toward Aspidospermatan-Type Alkaloids Using One-Pot Vilsmeier–Haack Cyclization and Azomethine Ylide Cycloaddition,"The development of a new one-pot reaction sequence afforded the tricyclic core of several aspidospermatan-type alkaloids from a linear, densely functionalized substrate. The key sequence features a highly chemoselective formamide activation that triggered a Vilsmeier-Haack cyclization, followed by an azomethine ylide generation and intramolecular cycloaddition. The choice of nucleophile, azomethine ylide precursor, and dipolarophile was crucial to the success of the sequence.",10.1021/acs.joc.7b00345,2017-04-18,0.5889806216531653
Tetrahedron,A facile and concise route toward the synthesis of novel imidazo-tetrazolodiazepinones via post-condensation modifications of the Ugi-azide adduct,,10.1016/j.tetlet.2015.07.083,2015-08-03,0.5889800277305712
Angewandte Chemie International Edition,Access to Multifunctionalized Benzofurans by Aryl Nickelation of Alkynes: Efficient Synthesis of the Anti‐Arrhythmic Drug Amiodarone,"Abstract An unconventional nickel‐catalyzed reaction was developed for the synthesis of multifunctionalized benzofurans from alkyne‐tethered phenolic esters. The transformation involves the generation of a nucleophilic vinyl Ni II species by the regioselective syn ‐aryl nickelation of an alkyne, which then undergoes an intramolecular cyclization with phenol ester to yield highly functionalized 1,1‐disubstituted alkenes with 3‐benzofuranyl and (hetero)aryl substituents. The methodology can be used for the late‐stage benzofuran incorporation of various drug molecules and natural products, such as 2‐propylvaleric acid, gemfibrozil, biotin, and lithocholic acid. Furthermore, this arylative cyclization method was successfully applied for the efficient synthesis of the anti‐arrhythmic drug amiodarone.",10.1002/anie.201909015,2019-08-23,0.5889738365900484
European Journal of Organic Chemistry,A Concise Atroposelective Formal Synthesis of (–)‐Steganone,"Abstract We describe herein the atroposelective formal synthesis of (–)‐steganone, a parent member of Steganotaenia araliacea dibenzocyclooctadiene lignan lactones. Our synthesis features an atropodiastereoselective biaryl Suzuki–Miyaura cross‐coupling reaction with de up to 99 % using as a chiral auxiliary an enantiopure and efficiently converted β‐hydroxy sulfoxide derivative.",10.1002/ejoc.201402761,2014-08-21,0.588972651505218
Journal of Organic Chemistry,"Asymmetric Synthesis of <i>trans</i>-2,3-Disubstituted Indoline Derivatives","A novel method for asymmetric synthesis of trans-2,3-disubstituted indolines has been developed. The strategy involves the (-)-sparteine-mediated electrophilic substitution of 2-benzyl N-pivaloylaniline with aromatic or α,β-unsaturated aldehydes and subsequent intramolecular nucleophilic substitution. The simple protocol for two-step process can produce highly enantioenriched indolines 3a-o up to 98:2 er.",10.1021/jo2023526,2011-12-10,0.5889719514041615
Angewandte Chemie International Edition,"Total Syntheses of Hyperforin and Papuaforins A–C, and Formal Synthesis of Nemorosone through a Gold(I)‐Catalyzed Carbocyclization","The remarkable biological activities of polyprenylated polycyclic acylphloroglucinols (PPAPs) combined with their highly decorated bicyclo[3.3.1]nonane-2,4,9-trione frameworks have inspired synthetic organic chemists over the last decade. The concise total syntheses of four natural products PPAPs; hyperforin and papuaforins A-C, and the formal synthesis of nemorosone are reported. Key to the realization of this strategy is the short and scalable synthesis of densely substituted PPAP scaffolds through a gold(I)-catalyzed 6-endo-dig carbocyclization of cyclic enol ethers for late-stage functionalization.",10.1002/anie.201403939,2014-05-18,0.5889716359718962
Angewandte Chemie International Edition,Enantioselective Synthesis of Inherently Chiral Calix[4]arenes via Catalytic Asymmetric Lower‐Rim Functionalization,"We report herein an efficient approach for the enantioselective synthesis of inherently chiral calix[4]arenes (ICCs) via chiral phosphoric acid (CPA)-catalyzed lower-rim asymmetric functionalization. With vinylidene ortho-quinone methides (VQMs) as the key intermediates, a stepwise asymmetric halo-cyclization strategy was applied to construct diverse inherently chiral calix[4]arenes bearing multiple C─C axially stereogenic elements with high enantio- and diastereoselectivities (up to 96% ee, all d.r. > 20:1). The obtained lower-rim functionalized products underwent further photocatalytic transformations to access novel inherently chiral naphthofuran-based calix[4]arene architectures. Further synthetic modifications and analysis of their photophysical/chiroptical properties demonstrated their potential in optoelectronic materials and related fields. Mechanistic studies reveal that the reaction proceeds via a stepwise process, with the stereoselectivity-determining step occurring in the first VQMs-mediated cyclization, and the second step constituting a chiral transfer process.",10.1002/anie.202518659,2025-10-20,0.5889714244810529
Tetrahedron,New synthetic strategy for preparation of the anticoagulant drug Rivaroxaban via an asymmetric Henry reaction,,10.1016/j.tetlet.2018.11.067,2018-11-26,0.5889708807216937
Journal of the American Chemical Society,"Total Syntheses of Scabrolide B, Ineleganolide, and Related Norcembranoids","Concise total syntheses of several 5/7/6 norcembranoids, including ineleganolide, scabrolide B, sinuscalide C, and fragilolide A have been achieved through a fragment coupling/ring closure approach. The central seven-membered ring was forged through sequential Mukaiyama-Michael/aldol reactions using norcarvone and a decorated bicyclic lactone incorporating a latent electrophile. Subsequent manipulations installed the reactive enedione motif and delivered scabrolide B in 11 steps from a chiral pool-derived enone. Finally, ineleganolide, sinuscalide C, and fragilolide A were each accessed in one additional step.",10.1021/jacs.4c16629,2024-12-20,0.5889685681100065
Synlett,Radical Cyclization Approach to 4-Oxo-2-azetidineacetic Acids: Synthesis of a Chiral Key Intermediate for Carbapenem Antibiotic PS-5,"All articles of this category α-Bromo amide 8 bearing phenyl and phenylthio substituents at the terminus of the N -vinylic bond underwent radical cyclization in a 4- exo-trig manner to give β-lactam 9 , which was transformed, via oxidation of its phenyl group, into the key intermediate 14 for the synthesis of (±)-PS-5. The chiral key intermediate 23 for (+)-PS-5 was also obtained via an asymmetric radical cyclization of bromide 16 bearing ( S )-1-phenylethyl group on the nitrogen atom. 4-oxo-2-azetidineacetic acid - ( S )-(-)-1-phenylethylamine - (+)-PS-5 - radical cyclization - ruthenium tetroxide oxidation",10.1055/s-1995-5143,1995-09-01,0.5889662964848171
Tetrahedron,Total synthesis of lycogarubin C utilizing the Kornfeld–Boger ring contraction,,10.1016/j.tetlet.2009.11.085,2009-11-28,0.5889662404576894
Angewandte Chemie International Edition,Enantioselective Synthesis of 2‐Oxindole Spirofused Lactones and Lactams by Heck/Carbonylative Cylization Sequences: Method Development and Applications,"An efficient one-pot assembly of all-carbon spiro-oxindole compounds from non-oxindole-based materials has been developed through a palladium-catalyzed asymmetric Heck/carbonylative lactonization and lactamization sequence. Diversified spirooxindole γ-and δ-lactones/lactams were accessed in high yields with good to excellent enantioselectivities (up to 99 % ee) under mild reaction conditions. The natural product coixspirolactam A was conveniently synthesized by applying the current methodology, and thus its absolute configuration was elucidated for the first time. Asymmetric synthesis of an effective CRTH2 receptor antagonist has also been demonstrated utilizing this method in the key step.",10.1002/anie.201904838,2019-05-10,0.5889645933262053
Tetrahedron,A facile one-pot protocol for the synthesis of tetrazolyl-tetrahydroisoquinolines via novel domino intramolecular cyclization/Ugi-azide sequence,,10.1016/j.tetlet.2014.10.076,2014-10-16,0.5889591717234968
Tetrahedron,"Stereocontrolled total synthesis of the chiral building block (3S,4R)-3- [(R)-1-hydroxyethyl]-4-acetyloxy-azetidin-2-one: a useful synthon for the synthesis of (+)-thienamycin, carbapenems and penems.",,10.1016/s0040-4039(00)61969-x,1985-01-01,0.5889580720616887
Tetrahedron,A new route to the crinane skeleton via the low-valent titanium-mediated double reduction of cyclic sulfonamides,"• Short route to multi-cyclic alkaloid skeleton. • Regioselectivity in alkene formation by elimination and in an intramolecular Heck reaction. • Sulfonamide group as both an amino protecting group and also as a temporary tether. • New application of low-valent titanium reduction. The construction of a benzo-fused tetracyclic sulfonamide, followed by its low-valent titanium-based reduction and subsequent conversion to racemic crinane is reported. The synthesis of the tetracyclic sulfonamide features a sulfonyl templated, regio- and diastereoselective intramolecular Heck reaction, which installs an all-carbon quaternary centre. Thereafter, a low-valent titanium reduction removes the sulfonyl group, liberating a 3-aryloctahydroindole. A Pictet-Spengler reaction then generates the targeted ethano-bridged phenanthridine core structure of the crinan alkaloids.",10.1016/j.tetlet.2024.155285,2024-08-31,0.5889555980319532
Tetrahedron,Synthetic studies on new sugar oxetanose: Synthesis of D-erythrooxetanose and its reaction with silylated adenine derivative,,10.1016/s0040-4039(00)94608-2,1990-01-01,0.5889438294649578
European Journal of Organic Chemistry,"A Facile Synthesis of Both Enantiomers of 6‐Acetoxy‐5‐hexadecanolide, a Major Component of Mosquito Oviposition Attractant Pheromones","Abstract The stereoselective synthesis of (–)‐(5 R ,6 S )‐ erythro ‐6‐acetoxy‐5‐hexadecanolide, the major component of a mosquito oviposition attractant pheromone, and its enantiomer are reported. The synthesis was completed over seven steps in 28 % overall yield by using Sharpless asymmetric epoxidation and ZrCl 4 ‐catalyzed cyclic acetal formation as the key steps. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2009)",10.1002/ejoc.200801134,2009-03-05,0.5889410525339841
Organic Letters,"4-Fluoro-2,4-methanoproline","The first fluorinated analogue of the naturally occurring 2,4-methanoproline, 4-fluoro-2,4-methanoproline, has been synthesized in five steps from commercially available methyl 2-fluoroacrylate through a photochemical cyclization as a key step in generating a 2-azabicyclo[2.1.1]hexane skeleton.",10.1021/ol902381w,2009-11-11,0.5889396158317453
Organic Letters,A Concise Asymmetric Total Synthesis of (+)-Epilupinine,"Asymmetric total synthesis of (+)-epilupinine was achieved in just three steps using only commercially available common reagents. The total synthesis involved alkylations of N-nosylamide, ozone oxidation, and sequential reactions of the removal of the nosyl group, intramolecular dehydrative condensation, intramolecular Mannich reaction catalyzed by l-proline, and a reduction.",10.1021/acs.orglett.9b00607,2019-04-09,0.5889341948674212
Organic Letters,Catalytic Asymmetric Total Synthesis of (+)-Caprazol,"Catalytic asymmetric total synthesis of caprazol, a lipo-nucleoside antibiotic, has been accomplished employing two of the stereoselective C-C bond forming reactions as key transformations. The stereochemistries of the β-hydroxy-α-aminoester moiety at the juncture of the uridine part and diazepanone part, and of the β-hydroxy-α-amino acid moiety embedded in the diazepanone system, were constructed using a diastereoselective isocyanoacetate aldol reaction (dr = 88:12) and an enantioselective anti-nitroaldol reaction catalyzed by a Nd/Na-chiral amide ligand (dr = 12:1, 95% ee), respectively.",10.1021/ol501397b,2014-06-04,0.5889309199875072
Tetrahedron,Novel synthesis of l-iduronic acid using trehalose as the disaccharidic starting material,,10.1016/s0040-4039(98)02662-8,1999-02-01,0.5889305282997879
Tetrahedron,Synthesis of novel axially chiral cyclic benzopolysulfides,,10.1016/j.tetlet.2007.05.117,2007-05-25,0.588929446371806
Synthesis,Synthesis of l-Ribose from d-Ribose by a Stereoconversion through Sequential Lactonization as the Key Transformation,"l-Ribose, a key precursor of various l-nucleosides can only be synthesized from other sugars or other non-sugar precursors. Herein, the study involves the synthesis of naturally rare l-ribose from readily available d-ribose. Though, many synthetic strategies are developed to meet the increasing demands of l-ribose, seeking innovation, a synthesis employing sequential lactonization as the key transformation was explored. This novel conversion involves protection, oxidation, sequential lactonization, reduction with DIBAL-H, and deprotection.",10.1055/s-0036-1588857,2017-06-20,0.5889293999193129
Organic Letters,A Concise Synthetic Route to the Stereotetrad Core of the Briarane Diterpenoids,"A concise synthesis (under 10 steps) of the stereotetrad core of the briarane diterpenoids is reported. This approach harnesses the unique reactivity of salicylate ester derived 2,5-cyclohexadienones to quickly build complexity. In particular, a highly diastereoselective acetylide conjugate addition/β-ketoester alkylation sequence was used to set the relative configuration of the C1 (quaternary) and C10 (tertiary) vicinal stereocenters. The sterochemical outcome of the β-ketoester alkylation appears to be governed by torsional steering in the transition state.",10.1021/acs.orglett.5b00816,2015-04-14,0.5889283293660209
Journal of the American Chemical Society,Enantioselective Synthesis of α-Aminoboronic Acid Derivatives via Copper-Catalyzed N-Alkylation,"Due to burgeoning interest in the pharmaceutical industry in exploiting optically active α-aminoboronic derivatives as bioisosteres of α-amino acid derivatives, the discovery of methods for their catalytic asymmetric synthesis is an important challenge. Herein, we establish that a chiral copper catalyst (generated in situ from commercially available components) can achieve the enantioselective synthesis of α-aminoboronic derivatives via the coupling of two readily available partners, a carbamate and a racemic α-chloroboronate ester. Furthermore, we describe mechanistic studies that played a key role in the development of this new method and that provide insight into the optimized process.",10.1021/jacs.3c00038,2023-02-06,0.5889242119525901
Synlett,Expedient Synthesis of Highly Functionalized Coumarin Derivatives through a Domino Reaction,The straightforward synthesis of novel pentacyclic and hexacyclic coumarin heterocycles in a one-pot domino reaction is described. The process enables the synthesis of diversified coumarins in high yields in a single step.,10.1055/s-0030-1258490,2010-07-09,0.5889236359401858
Journal of Organic Chemistry,"Fluorination-Free Synthesis of a 4,4-Difluoro-3,3-Dimethylproline Derivative","A Claisen rearrangement/iodolactamization sequence starting from commercially available trifluoroacetaldehyde methyl hemiacetal, followed by a classical chemical resolution, provided enantiomerically pure 4,4-difluoro-3,3-dimethylproline (S)-1. No hazardous fluorination reagents were used, and the overall yield over 12 steps was greater than 28%.",10.1021/jo060057p,2006-06-20,0.5889231931775879
Journal of Organic Chemistry,"Studies toward Total Synthesis of (±)-Caldaphnidine C via One-Pot Sequential Intramolecular Vilsmeier–Haack and Azomethine Ylide 1,3-Dipolar Cycloaddition","An application of a one-pot sequential Vilsmeier-Haack cyclization and intramolecular azomethine ylide 1,3-dipolar cycloaddition toward the total synthesis of (±)-caldaphnidine C is presented. It allowed an efficient formation of three cycles with perfect control of four of the five newly created stereogenic centers including one all-carbon quaternary center. Two synthetic strategies to produce the key-step precursor, the investigation and optimization of the cyclization partners (nucleophile, azomethine ylide, and dipolarophile), and further derivatization of the cycloadduct are reported.",10.1021/acs.joc.6b01835,2016-09-19,0.58891939414066
Tetrahedron,Concise synthesis of the DEFG ring system in rubriflordilactone B,,10.1016/j.tetlet.2015.05.117,2015-06-06,0.5889182850323492
Organic Letters,Synthesis of 2-(2-Pyridyl)-2<i>H</i>-azirines via Metal-Free C–C Cross-Coupling of Bromoazirines with 2-Stannylpyridines,"A high-yield method for the introduction of a 2-pyridyl substituent in the C2 position of the three-membered ring of 2-bromo-2 H -azirine-2-carboxylic acid derivatives by the direct cross-coupling with 2-(trialkylstannyl)pyridines has been described. The reaction works well with 3-, 4-, or 5-substituted 2-stannylpyridines and can be also employed for the synthesis of 2-(thiazol-2-yl)-2 H -azirines. According to DFT calculations, the reaction proceeds through the sequence of S N 2′-substitution of bromine, 1,4-stannyl shift, and [2,3]-sigmatropic shift of the pyridine ring.",10.1021/acs.orglett.1c03060,2021-10-01,0.588917935958159
Tetrahedron,"First asymmetric enantioselective total synthesis of phenanthridine alkaloid, (S)-(+)-asiaticumine and its enantiomer",,10.1016/j.tetlet.2019.151278,2019-10-14,0.5889152408061727
Tetrahedron,A novel synthesis of pyrimidopteridine-10-oxides,,10.1016/s0040-4039(01)97417-9,1971-01-01,0.5889148621269452
Synthesis,"A Novel Synthesis of 2,4,10-Trioxa-3-silaadamantanes",,10.1055/s-1984-30907,1984-01-01,0.5889148621269452
Tetrahedron,"Synthesis and novel reactivities of several 1,9-dithiaalkane-bridged thianthrene 10-oxides",,10.1016/j.tetlet.2008.12.116,2009-01-10,0.5889148621269452
Tetrahedron,"Synthesis of N-(2-methylpropyl)-2E-undecene-8,10-diynamide, a novel constituent of Echinacea angustifolia",,10.1016/s0040-4039(03)01253-x,2003-06-30,0.5889148621269452
Green Chemistry,"Electroenzymatic cascade synthesis of 2,3-diaminophenazine on HRP-ZnGa <sub>2</sub> O <sub>4</sub> nano-biohybrids","In this work, a novel nano-biohybrid has been developed for the efficient synthesis of 2,3-diaminophenazine (DAP), a biologically significant heterocyclic compound, via an electroenzymatic cascade catalysis system.",10.1039/d5gc03726c,2025-01-01,0.588906303610666
Journal of Organic Chemistry,Copper(I)-Catalyzed Highly Efficient Synthesis of Benzoselenazoles and Benzotellurazoles,"A simple and practical useful synthetic method of 1,3-benzoselenazoles having a heteroatom substituent such as NRR', OR, and SR groups at the 2-position was developed by the copper(I)-catalyzed reaction of 2-bromophenyl (1) or 2-iodophenyl (2) isocyanides with selenium and heteroatom nucleophiles. In addition, the synthesis of 2-amino-1,3-benzotellurazoles is also described.",10.1021/jo7013164,2007-09-15,0.5888993845578948
Journal of Organic Chemistry,Synthesis of Homoverrucosanoid-Derived Esters and Evaluation as MDR Modulators,"The synthesis of the A-B-cis,B-C-trans-annulated cyclohepta[e]hydrindane core of a gagunin E analogue is reported in detail. The tricarbocyclic scaffold was assembled starting from an easily accessible A ring building block by a (4 + 2)-cycloaddition for annulation of the B ring. A ring-closing metathesis served for construction of the seven-membered C ring. The angular methyl groups were attached by electrophilic cyclopropanation-ring opening. A library based on the most active lead compound was made accessible by esterification of the terpenols with commercially available acids. A transannular etherification reaction gave access to tetracyclic derivatives of the synthetic inhibitors. The members of the compound library of non-natural homoverrucosanoid-derived esters were examined as modulators of the membrane transporter proteins ABCB1 (P-gp), ABCG2 (BCRP), and ABCC1 (MRP1), which are involved in the formation of multidrug resistance (MDR) in cancer chemotherapy.",10.1021/acs.joc.7b02012,2017-09-26,0.5888989252323763
Angewandte Chemie International Edition,Gold(I)‐Catalyzed Bis‐Spiroketalization: Synthesis of the Trioxadispiroketal‐Containing A–D Rings of Azaspiracid,"Au-dacious ring synthesis: An efficient synthesis of the A–D rings of azaspiracid has been developed by using a Co-catalyzed oxaetherification to form the fused 2,5-trans-configured trisubstituted tetrahydrofuran D ring, and an unprecedented Au-catalyzed bis-spiroketal formation wherein a bridging alkyne served as a surrogate for the C10 ketal (see scheme; PMB=para-methoxybenzyl, TBDPS=tert-butyldiphenylsilyl).",10.1002/anie.200601963,2006-12-04,0.5888984856861463
Organic Process Research & Development,"Chemical and Biochemical Approaches to an Enantiomerically Pure 3,4-Disubstituted Tetrahydrofuran Derivative at a Multikilogram Scale: The Power of KRED","A scalable synthesis of ( 3S,4S )-4-methyltetrahydrofuran-3-ol involving a keto reductase-mediated enantio- and diastereoselective reduction of a racemic ketone substrate is reported. This chiral intermediate was initially produced using a low-yielding three-step synthesis from ketone, deemed not usable for future batches. Looking for a scalable and environmental process: an eco-design approach led to a one-step, highly enantio- and diastereoselective biocatalytic reduction of the ketone to the targeted intermediate (3 S,4 S )-4-methyltetrahydrofuran-3-ol. In addition, the reaction operates via dynamic kinetic resolution under unprecedented mild conditions of temperature and pH, allowing for a full conversion of the ketone substrate into the desired enantiomer. The new route led to a significant improvement of all the key performance indicators, including PMI, solvent, and waste.",10.1021/acs.oprd.4c00388,2024-11-14,0.5888961821538604
Tetrahedron,"An efficient route to 5-(hetero)aryl-2,4′- and 2,2′-bipyridines through readily available 3-pyridyl-1,2,4-triazines",,10.1016/j.tetlet.2005.01.135,2005-02-10,0.5888913782880356
Journal of Organic Chemistry,Electrophilic Cyclization of Aryldiacetylenes in the Synthesis of Functionalized Enediynes Fused to a Heterocyclic Core,"An efficient strategy for the synthesis of asymmetrically substituted enediynes fused to benzothiophene, benzofuran, and indole was developed. The proposed approach is based on the electrophilic cyclization of diacetylenes and Sonogashira coupling. Thus, iodocyclization of readily available ortho-functionalized (buta-1,3-diynyl)arenes was used as a direct way for the synthesis of 2-ethynyl-3-iodoheteroindenes. These substrates and their modified derivatives were easily converted by Sonogashira coupling with acetylenes to a variety of asymmetrically substituted acyclic enediynes fused to heterocycles. The tolerance of the developed methodology to a variety of functional groups is a great advantage in the synthesis of macrocyclic enediyne systems fused to a heterocyclic core. Synthesis of indole-fused 12-membered macrocyclic dienediyne was achieved using ring-closing metathesis as a key step.",10.1021/jo501396s,2014-08-27,0.5888902025438871
Organic Letters,Synthesis of Diazatricyclic Common Structure of Madangamine Alkaloids,"A general synthetic route toward a diazatricyclic core common to the madangamine family is described. Ring-closing metathesis and palladium-catalyzed cycloisomerization provided the cis-fused diazadecalin structure, accompanied by formation of the N-Boc-enamine, which was utilized as an N-acyliminium ion equivalent. Direct cyclization from the N-Boc-enamine was achieved through the in situ formation of an N,O-acetal.",10.1021/acs.orglett.5b00661,2015-03-27,0.5888755690031064
Tetrahedron,Synthetic studies on manzamine A: construction of a key bicyclic AD ring subunit I,,10.1016/0040-4039(94)88286-x,1994-10-01,0.5888749716519197
Angewandte Chemie International Edition,"Synthesis of Axially Chiral Biaryls via Enantioselective Ullmann Coupling of<i>ortho</i>‐Chlorinated Aryl Aldehydes Enabled by a Chiral 2,2′‐Bipyridine Ligand","The first nickel-catalyzed highly enantioselective reductive Ullmann coupling of ortho-chlorinated aryl aldehyde was achieved under mild reaction conditions with a chiral 2,2'-bipyridine ligand (+)-DTB-SBpy, thus providing axially chiral biphenyl or binaphthyl dials with up to 99 % yield and 99.5:0.5 er. The versatility of the products as common synthetic intermediates for diverse axially chiral ligands, catalysts, and functional molecules was demonstrated by short-step transformations. This protocol also allowed the concise and highly enantioselective formal total synthesis of biologically active natural products (+)-kotanin, (-)-isoschizandrin and (+)-gossypol.",10.1002/anie.202212108,2022-10-05,0.58887382560057
Tetrahedron,Corrigendum to “Large scale synthesis of acetylene dicarboxaldehyde mono and diacetal”,,10.1016/j.tetlet.2005.01.090,2005-02-02,0.5888720798491618
Tetrahedron,Large scale synthesis of acetylene dicarboxaldehyde mono and diacetal,,10.1016/j.tetlet.2004.01.022,2004-01-23,0.5888720798491618
Journal of Organic Chemistry,Concise Total Syntheses of (±)-Strychnine and (±)-Akuammicine,"Concise total syntheses of Strychnos alkaloids strychnine (1) and akuammicine (2) have been realized in 13 and 6 operations, respectively. Key steps include (1) the vinylogous Mannich reaction; (2) a novel, sequential one-pot spirocyclization/intramolecular aza-Baylis-Hillman reaction; and (3) a Heck cyclization. The synthesis of 1 proceeds via the Wieland-Gumlich aldehyde (26).",10.1021/jo100516g,2010-04-22,0.5888682965826899
Journal of Organic Chemistry,"Synthesis of Tryptamine Derivatives via a Direct, One-Pot Reductive Alkylation of Indoles","An efficient, one-pot reductive alkylation of indoles with N-protected aminoethyl acetals in the presence of TES/TFA is reported. It represents the first general method for the direct synthesis of tryptamine derivatives from indoles and nitrogen-functionalized acetals. This convergent and versatile approach employs safe and inexpensive reagents, proceeds under mild conditions, and tolerates several functional groups. The new procedure was efficiently applied to a gram-scale synthesis of both luzindole, a reference MT2-selective melatonin receptor antagonist, and melatonin.",10.1021/jo3010028,2012-06-22,0.5888653114120849
Tetrahedron,"Synthesis and reactions of chiral 5-substituted (Z)-ethyl 2-bromo-3-(1,3-dioxolan-4-yl)-2-propenoates",,10.1016/s0040-4039(97)01648-1,1997-10-01,0.5888641525758391
Tetrahedron,A route to acyclic tricarbonyl(η5-trienyl)iron(1+) complexes for use in polyene asymmetric synthesis,,10.1016/s0040-4039(00)92360-8,1991-09-01,0.5888565007494376
Angewandte Chemie International Edition,Total Synthesis of (+)‐Neopeltolide by a Prins Macrocyclization,Rings within rings: The total synthesis of (+)-neopeltolide was accomplished by employing an intramolecular Prins macrocyclization of an aldehydic homoallylic alcohol intermediate (see scheme).,10.1002/anie.200800386,2008-03-17,0.5888557913727795
Tetrahedron,Efficient synthesis of the revised structure of (−)-galantinic acid.,,10.1016/s0040-4039(00)97567-1,1990-01-01,0.5888513063757417
Organic Letters,"Enantio- and Diastereoselective Synthesis of 1,5-<i>syn</i>-(<i>Z</i>)-Amino Alcohols via Imine Double Allylboration: Synthesis of <i>trans</i>-1,2,3,6-Tetrahydropyridines and Total Synthesis of Andrachcine","A stereoselective synthesis of trans-1,2,3,6-tetrahydropyridines 8 is described. This synthesis proceeds via intramolecular Mistunobu reactions of 1,5-syn-(Z)-amino alcohols 7, which were prepared by a highly diastereo- and enantioselective double-allylboration reaction of aldehyde 5 and silylimine 6. The chiral bifunctional γ-borylallylborane 9E was generated in situ by hydroboration of allene 3 with (diisopinocampheyl)borane 4. This strategy was applied to the total synthesis of andrachcine 1, thus establishing with certainty the absolute and relative configuration of the natural product.",10.1021/acs.orglett.7b00995,2017-05-04,0.5888512737358506
Tetrahedron,Synthesis and reactivity of protected β-bromo α-iminoacids; a convenient route to structurally diversified aminoacids.,,10.1016/s0040-4039(00)97458-6,1990-01-01,0.5888474524408875
Synthesis,"Stereoselective Approaches for the Total Synthesis of Polyacetylenic (3<i>R</i>,8<i>S</i>)-Falcarindiol",The total synthesis of the polyacetylenic compound falcarindiol was achieved by two different routes from a common intermediate.,10.1055/s-2007-990944,2007-12-20,0.5888430030681573
Tetrahedron,Total synthesis of MS-444: A myosin light chain kinase and HuR inhibitor from Micromonospora sp. KY7123,,10.1016/j.tetlet.2021.153328,2021-08-18,0.5888406601197514
Journal of Organic Chemistry,Spiropiperidine Sultam and Lactam Templates: Diastereoselective Overman Rearrangement and Metathesis followed by NH Arylation,"We report the diastereoselective synthesis of novel spiropiperidine templates for use in SAR studies of β-secretase (BACE) inhibitors and also as versatile ligands for other receptor types. The overall synthetic approach stems from chiral starting material benzyl (S)-2-methyl-4-oxopiperidine-1-carboxylate and employs an Overman rearrangement to control the stereochemistry at the quaternary center. This process is followed by a Grubbs metathesis to close a five-membered ""top"" ring to form an α,β-unsaturated lactam or an α,β-unsaturated sultam. We also demonstrate that this chemistry can accommodate additional substituents on the lactam/sultam ring and allows late stage sequential functionalization of the amine and amide nitrogens to rapidly produce diverse analogues.",10.1021/acs.joc.7b02096,2017-11-03,0.5888362679873641
Organic Letters,"Convergent Syntheses of 3,6-Dihydroxydec-4-enolides","The total syntheses of the 3,6-dihydroxydecanolide from Cordyceps militaris and the novel C-3 epimer are reported using a diastereoselective Nozaki-Hiyama-Kishi reaction in the key cyclization to generate the 6R stereocenter.",10.1021/ol3018566,2012-07-31,0.5888353070838992
Synthesis,Efficient Synthesis of Heterocyclic Neurotensin Receptor Ligands by Microwave-Assisted Aminocarbonylation,"Marking the heterocyclic neurotensin receptor antagonist SR142948A as a lead compound, the development of an efficient and a practical synthetic route to heterocyclic aryl carboxamides is reported. Thus, a highly efficient and flexible access to these carboxamides was elaborated by taking advantage of microwave-assisted aminocarbonylation reaction mediated by Mo(CO) 6 , Herrmann’s palladacycle, [( t -Bu) 3 PH]BF 4 , and DBU.",10.1055/s-0033-1338497,2013-07-11,0.5888293351318676
Journal of Organic Chemistry,Diastereoselective Construction of Quaternary Carbons Directed via Macrocyclic Ring Conformation:  Formal Synthesis of (−)-Mesembrine,"In this article, we report a highly diastereoselective new method for the generation of quaternary carbon centers through an anionic oxy-Cope/alkylation sequence where the diastereoselectivity is induced by the conformation of a macrocyclic tetrasubstituted enolate. The use of our methodology culminated in the formal total synthesis of (-)-mesembrine (34) in 11 steps from known starting materials.",10.1021/jo701833v,2007-10-24,0.5888283752144244
Journal of Organic Chemistry,"Flexible Total Synthesis of (±)-Aureothin, a Potent Antiproliferative Agent","Amenable to late-stage preparation of analogues, a flexible and convergent total synthesis of (±)-aureothin is presented. The strategy was based on a desymmetrization of α,α'-dimethoxy-γ-pyrone by a process combining 1,4-addition and alkylation of vinylogous enolate to stereoselectively reach the backbone of the target. Palladium-catalyzed cyanation of an elaborated and isomerizable E,Z dienyl motif followed by Pinner cyclization enabled the construction of the tetrahydrofuran motif while a first approach based on a late-stage oxidation was unsuccessful.",10.1021/acs.joc.6b00878,2016-05-23,0.5888265156645223
Tetrahedron,Generation of chlorofluorocarbene by dehalogenation of fluorotrichloromethane with reduced titanium. A new synthesis of 1-chloro-1-fluorocyclopropanes.,,10.1016/s0040-4039(00)82445-4,1988-01-01,0.5888139245793479
Synlett,"A Short, Efficient, and Stereoselective Synthesis of Piperine and its Analogues",A quantitative synthesis of piperine from commercially available starting material is presented. The synthesis relies on a stereoselective nucleophilic attack of an in situ generated cuprate onto a cyclobutene lactone. The so-formed aryl-substituted cyclobutene spontaneously undergoes a conrotatory 4π-electrocyclic ring opening to form the 4-aryl pentadienoic acid as a single diastereoisomer. The high-yielding synthesis can be easily modulated on the aryl and on the amide moiety for the synthesis of a wide range of piperine analogues.,10.1055/s-0037-1611652,2019-01-14,0.5888132621737987
Synthesis,A New Enantioselective Synthesis of the Anti-Parkinson Agent Safinamide,"An alternative highly enantioselective synthesis of the anti-Parkinson agent safinamide from simple, commercially available, starting materials is described. The protocol might also be useful in the synthesis of structural variants of safinamide, such as ralfinamide or related analogues",10.1055/s-0033-1341104,2014-04-02,0.5888095127126604
European Journal of Organic Chemistry,Intramolecular Tandem Isomerization–Mannich Reaction as a New Route Towards Aminocyclopentitols,"Abstract A new efficient synthetic strategy has been developed to prepare aminocyclopentitols. It is based on an iron‐catalyzed tandem isomerization–Mannich reaction and uses chiral N ‐ tert ‐butanesulfinamide as a chiral auxiliary. This methodology has been applied to the enantiocontrolled synthesis of a mannostatin A analogue, as well as isomers of known fucosidase and glycosidase inhibitors.",10.1002/ejoc.201101130,2011-10-11,0.5888091983407386
Journal of Organic Chemistry,Total Synthesis of (+)-Crocacin D,"[structure: see text] The total synthesis of (+)-crocacin D is described. The convergent asymmetric synthesis relies on the use of a Stille cross-coupling between an (E)-vinyl stannane with an (E)-vinyl iodide to establish the (E,E)-dienamide moiety followed by a mild and efficient copper-catalyzed coupling between (+)-crocacin C and a (Z)-vinyl iodide to establish the challenging (Z)-enamide function.",10.1021/jo047732k,2005-02-17,0.588803779956636
Journal of Organic Chemistry,Total Synthesis of (±)/(+)-Subincanadine E and Determination of Absolute Configuration,"A facile synthesis of (±)-subincanadine E was described from tryptamine-based maleimide. 1,2-Addition of Grignard reagent to maleimide, internal activation of formed lactamol for in situ 1,4-addition of Grignard reagent, and associated position-specific allylic rearrangement in diastereoselective Pictet-Spengler cyclization were the key steps. Enantioselective first total synthesis of naturally occurring cytotoxic (+)-subincanadine E was also accomplished from (S)-acetoxysuccinimide via an unusual syn-addition of cuprate to the α,β-unsaturated lactam. Sinister absolute configuration was assigned to (+)-subincanadine E on the basis of total synthesis. (S)-Acetoxy group in the succinimide precursor was initially employed to impart regio- and stereoselectivity and then as a suitable leaving group to generate the desired conjugated lactam.",10.1021/acs.joc.7b02122,2017-09-27,0.5888009403939696
Tetrahedron,New Route to 3-Deoxy-2-Ulosonic Acids; Total Syntheses of KDO and KDN,,10.1016/s0040-4039(97)01484-6,1997-09-01,0.5887942410904943
Organic Letters,Synthesis of Proposed Aglycone of Mandelalide A,"A highly convergent synthesis of the proposed mandelalide A aglycone is reported. The cornerstones of the synthetic strategy include the following: E-selective intramolecular Heck cyclization, Masamune-Roush olefination, Stork-Zhao-Wittig olefination, modified Prins cyclization; Sharpless asymmetric dihydroxylation followed by Williamson-type etherification, Julia-Kocienski olefination, Brown crotylation, and Brown allylation reactions.",10.1021/ol500875e,2014-04-16,0.5887935501489945
Journal of Organic Chemistry,"Cationic Cyclization of 2-Alkenyl-1,3-dithiolanes: Diastereoselective Synthesis of <i>trans</i>-Decalins","An unprecedented and highly diastereoselective 6-endo-trig cyclization of 2-alkenyl-1,3-dithiolanes has been developed yielding trans-decalins, an important scaffold present in numerous di- and triterpenes. The novelty of this 6-endo-trig cyclization stands in the stepwise mechanism involving 2-alkenyl-1,3-dithiolane, acting as a novel latent initiator. It is suggested that the thioketal opens temporarily under the influence of TMSOTf, triggering the cationic 6-endo-trig cyclization, and closes after C-C bond formation and diastereoselective protonation to terminate the process. DFT calculations confirm this mechanistic proposal and provide a rationale for the observed diastereoselectivity. The reaction tolerates a wide range of functionalities and nucleophilic partners within the substrate. We have also shown that the one-pot 6-endo-trig cyclization followed by in situ 1,3-dithiolane deprotection afford directly the corresponding ketone. This improvement allowed the achievement of the shortest total synthesis of triptophenolide and the shortest formal synthesis of triptolide.",10.1021/jo2001116,2011-03-29,0.588790894931646
Organic Letters,Short Synthesis of Octosyl Nucleosides,"[reaction: see text] Commercial 1,2:5,6-di-O-isopropylidene-alpha-d-allofuranose was converted to a protected bicyclic octosyl acid thioglycoside donor by a 10-step sequence that features an intramolecular ester enolate alkylation. Glycosylation of N-benzoyladenine and methyl uridine-5-carboxylate followed by deprotection gave the respective nucleosides ""octosyl adenine"" and octosyl acid A.",10.1021/ol0600382,2006-03-01,0.5887897882034161
Synlett,Synthesis of Ferrocene Bridged<i>bis</i>(2-Indenyl) Ligands,"An optimised synthesis of 1,1′-bis(2-indenyl)ferrocene in 47% yield from the Pd(0)-catalysed cross coupling between 1,1′-zincated ferrocene and 2-bromo-indene is described along with the formation of (2-indenyl) ferrocene in 40% yield. The analogous synthesis of planar chiral derivatives gave either pure N,N-dimethyl-1-[2-(2-indenyl)ferrocenyl]ethylamine (74%) or N,N-dimethyl-1-[2,1′-bis(2-indenyl)ferrocenyl]ethylamine (26%) dependent upon the amount of Pd(0) catalyst used.",10.1055/s-2002-33524,2002-01-01,0.5887858351968842
Journal of Organic Chemistry,Total Syntheses of the Benzodiazepine Alkaloids Circumdatin F and Circumdatin C,"Total syntheses of circumdatin F and circumdatin C, which both possess a 3H-quinazolin-4-one as well as a 1,4-benzodiazepin-5-one moiety, are described. A tripeptide derivative was synthesized as a key intermediate and dehydrated to a benzoxazine by reaction with triphenylphosphine, iodine, and a tertiary amine. The natural products were attained via rearrangements to an amidine intermediate, deprotection with 45% HBr in acetic acid, and cyclization on silica gel.",10.1021/jo001696h,2001-03-22,0.5887837231771232
Organic Letters,"Total Synthesis of Munchiwarin, a Triprenylated Chalcone from <i>Crotalaria medicagenia</i>","An efficient method is developed for the synthesis of the modified triprenylated chalcone, munchiwarin (1), isolated from the roots of Crotalaria medicagenia. The synthesis of 1 utilizes a Claisen-Schmidt condensation between 2,4-dihydroxy-3,5-C-diprenyl acetophenone and 4-methoxy benzaldehyde in the presence of Ba(OH)2 to yield the unusual chalcone 5 that contains a nine-membered ether ring. Further prenylation of 5 with 1-bromo-3-methylbut-2-ene and its subsequent demethylation with BBr3 gave munchiwarin (1).",10.1021/ol702187m,2007-11-22,0.5887832630841505
Angewandte Chemie International Edition,AgF‐Mediated Fluorinative Cross‐Coupling of Two Olefins: Facile Access to α‐CF<sub>3</sub> Alkenes and β‐CF<sub>3</sub> Ketones,"A AgF-mediated fluorination with a concomitant cross-coupling between a gem-difluoroolefin and a non-fluorinated olefin is reported. This highly efficient method provides facile access to both α-CF3 alkenes and β-CF3 ketones, which otherwise remain challenging to be directly prepared. The application of this method is further demonstrated by the synthesis of bioactive isoxazoline derivatives. This approach represents a conceptually novel route to trifluoromethylated compounds that combines the in situ generation of the CF3 moiety and a C-H functionalization in a single reaction system.",10.1002/anie.201409705,2014-11-12,0.5887820952735998
Tetrahedron,"New synthesis of cis-3,4-diaryl-1-tosylpyrrolidines",,10.1016/j.tetlet.2006.03.141,2006-04-18,0.5887803652289587
Synthesis,"A New Synthesis of<i>cis</i>-3,5-Diacetoxycyclopentene",,10.1055/s-1974-23454,1974-01-01,0.5887803652289587
Tetrahedron,A practical synthesis of trans-iodoolefins,,10.1016/s0040-4039(00)85058-3,1986-01-01,0.5887761997299107
Organic Process Research & Development,A Practical and Efficient Process for the Preparation of Tazarotene,"We describe an efficient process for the preparation of tazarotene starting from 4,4-dimethyl-6-bromothiochromane S -oxide ( 9 ), 2-methyl-3-butyn-2-ol ( 10 ), and 6-chloronicotinic acid ethyl ester ( 8 ). Our synthetic pathway compares favorably over the previously reported procedures since tazarotene was prepared straightforwardly using cheap reagents and without the employment of hazardous organometallic compounds. The process is based on the use of sulfoxide 9 as key starting material. The C-15 framework of the target was built up by means of two different approaches based on a palladium-mediated coupling reaction. The molecular structure of compound has been confirmed by X-ray crystallography.",10.1021/op050080x,2005-07-26,0.5887707570182243
Synthesis,"An Improved Synthesis of (24<i>R</i>)-24,25-Dihydroxyprovitamin D<sub>3</sub> <sup>1</sup>","All articles of this category (24 R )-24,25-Dihydroxyprovitamin D 3 was prepared in 33% overall yield by a six-step procedure starting from the Diels-Alder adduct of ergosteryl benzoate and 1,4-dihydrophthalazine-1,4-dione. The yield thus obtained is more than four times as high as that of an eight-step synthesis based on the Diels-Alder adduct of ergosteryl acetate and 4-phenyl-1,2,4-triazoline-3,5-dione. The combination of the benzoyl group and the 1,4-dioxo-1,2,3,4-tetrahydrophthalazin-2,3-diyl group for the protection of the 3ß-hydroxy group and the 5,7-diene system, respectively, did not only raise the yield of the crucial ozonization step to 87% but was also advantageous in that it diminished the air and light sensitivity of the intermediates in the following reaction steps.",10.1055/s-1990-26826,1990-01-01,0.5887676325213684
Tetrahedron,Koenigs-knorr synthesis of part of the immunodeterminant group in a streptococcal polysaccharide: 2-o-α-l-rhamnopyranosyl-l-rhamnopyranose,,10.1016/s0040-4039(01)95168-8,1978-01-01,0.588764445480584
Tetrahedron,Synthesis of unsymmetrical spermine alkaloids of the group,,10.1016/s0040-4039(00)85156-4,1986-01-01,0.588764445480584
Tetrahedron,Synthesis of triantennary blood group I antigens: Neolacto-glycopentadecaosyl ceramide,,10.1016/s0040-4039(00)60969-3,1992-10-01,0.588764445480584
European Journal of Organic Chemistry,"Practical First Total Synthesis of the Potent Phytotoxic (±)‐Naphthotectone, Isolated from <i>Tectona grandis</i>","Abstract Naphthotectone is a quinone isolated recently from teak extracts of Tectona grandis . It has been shown to be one of the most abundant compounds and the most active compound isolated form teak. Thus, it has been proposed that naphthotectone is one of the compounds responsible for the allelophathic activity of this plant. An efficient total synthesis of (±)‐naphthotectone was achieved in seven steps and 31 % overall yield. The best results were obtained by using an aqueous Wittig reaction as a key step. Other reactions used were the formation of an epoxide ring by the Corey–Chaykovsky method, and an innovative one‐pot anodic electrooxidation and demethylation.",10.1002/ejoc.201300783,2013-08-05,0.5887624919468192
Synthesis,Facile Synthesis of Coumarin- and Quinolone-Annulated Benzazoninone Derivatives by an Intramolecular Heck Reaction Strategy via 9-exo-trig Cyclization,A synthetic strategy based on the application of the aromatic aza-Claisen rearrangement followed by an intramolecular Heck reaction sequence as the key step has been developed for the regiocontrolled synthesis of hitherto unreported coumarin- and quinolone­-annulated benzazoninone derivatives in 48-69% yield.,10.1055/s-0030-1260005,2011-04-15,0.5887588206110956
Tetrahedron,A new synthetic approach for novel 4-substituted-5-nitroimidazoles,,10.1016/s0040-4039(02)00767-0,2002-06-01,0.5887574137587989
Tetrahedron,A new synthetic approach for novel C-3 substituted β-lactams,,10.1016/s0040-4039(00)00865-0,2000-07-01,0.5887574137587989
Synlett,Enantioselective Synthesis of Indole Alkaloids from Chiral Lactams,"This account reports on the use of (R)- or (S)-phenylglycinol- and (S)-tryptophanol-derived oxazolopiperidone lactams as building blocks for the enantioselective synthesis of structurally diverse indole alkaloids. 1 Introduction 2 Monoterpenoid Indole Alkaloids from (R)- or (S)-Phenyl­glycinol-Derived Lactams 2.1 Substituted Piperidines as Precursors for the Enantioselective Synthesis of Indole Alkaloids 2.1.1 (+)-Decarbomethoxytetrahydrosecodine 2.1.2 Enantiopure cis- and trans-(3-Ethylpiperidin-4-yl)acetates as Precursors for the Synthesis of Indolo- and Benzo-[a]quinolizidine Alkaloids 2.1.3 Indole Alkaloids Related to Cleavamine and Quebrach-amine 2.2 Uleine and Strychnos Alkaloids 2.3 The Ervatamine-Silicine Group 3 Indolo[2,3-a]quinolizidines from (S)-Tryptophanol-­Derived Lactams 3.1 Indolo[2,3-a]quinolizidines and Analogues by Intramolecular Amidoalkylation Reactions: Synthesis of (R)-(+)-­Deplancheine and (R)-(+)-Harmicine 3.2 Indolo[2,3-a]quinolizidines by a Modified Bischler-­Napieralski Reaction: Formal Synthesis of (+)-Dihydro­corynantheine and (-)-Dihydrocorynantheol 4 Conclusion",10.1055/s-0030-1259297,2011-01-01,0.588755299617417
Angewandte Chemie International Edition,Total Synthesis of the Hamigerans,"The first total synthesis of hamigerans D, G, L, and N-Q has been accomplished. A convergent approach was used to build the basic tricarbocyclic ring system bearing a 5-6-6 structure. A sequence of oxidative cleavage, homologation, and ring regeneration provided access to the 5-7-6 skeleton of hamigeran G. Based on the biogenetic hypothesis, elegant and highly efficient biomimetic transformations of hamigeran G into hamigerans D, N-Q, and L were achieved.",10.1002/anie.201604070,2016-07-08,0.5887529379238698
Organic Process Research & Development,First Multikilogram Synthesis of the Next-Generation Oral Selective ERα Degrader Camizestrant,"Camizestrant is currently being investigated in multiple Phase 3 clinical trials for ER+ breast cancer. This article describes our efforts toward the first manufacture of clinical material. Strategic process development focused on delivering robust processes and control points that could be scaled to deliver kilograms of material of the right quality and meet expedited project timelines. Highlights include optimization of an efficient Buchwald–Hartwig amination, development of a diastereoselective Pictet–Spengler reaction followed by an efficient isolation, and a significant reduction in the number of chromatography stages from five to one. The processes were used to deliver 8.5 kg of material in an overall yield of 44%.",10.1021/acs.oprd.4c00135,2024-06-07,0.5887463756511133
Organic Letters,Synthesis of Optically Active α-Aminoalkyl α‘-Halomethyl Ketone: A Cross-Claisen Condensation Approach,"A simple and versatile method was developed for the synthesis of alpha-aminoalkyl alpha'-halomethyl ketone derivatives, which are useful intermediates of protease inhibitors. It involves selective halogenation of the alpha-position on a beta-ketoester, which is prepared by cross-Claisen condensation using N-protected amino acid ester. The title compound is obtained in high yield after decarboxylation of the alpha-halo-beta-ketoester.",10.1021/ol017163s,2002-01-05,0.5887460890449469
Organic Letters,A Total Synthesis of Tarchonanthuslactone Exploiting <i>N</i>-Pyrrole Carbinols as Efficient Stereocontrolling Elements,"[reaction: see text] A short stereoselective total synthesis of the polyketide natural product, tarchonanthuslactone, has been achieved. The key sequence involves the first reported catalytic enantioselective reduction of an N-acyl pyrrole and subsequent use of this stereocenter in a diastereoselective reductive cascade. This proceeded with unprecedentedly high stereocontrol and offered an elegant method of generating the desired syn stereochemistry present in the final target in one step.",10.1021/ol052333c,2005-11-30,0.588742711989484
Journal of Organic Chemistry,Diastereoselective Addition of PhSCF<sub>2</sub>SiMe<sub>3</sub> to Chiral <i>N</i>-<i>tert</i>-Butanesulfinyl Ketimines Derived from Isatins: Synthesis of Enantioenriched <i>gem</i>-Difluoromethylenated Spiro-pyrrolidinyl and Spiro-piperidinyl Oxindoles,"A convenient and efficient synthetic strategy to prepare enantioenriched gem -difluoromethylenated spiro-pyrrolidinyl and spiro-piperidinyl oxindoles is described. Fluoride-mediated diastereoselective nucleophilic addition of PhSCF 2 SiMe 3 to chiral N - tert -butanesulfinyl ketimines derived from isatins was a key step and provided diastereomeric adducts, which were readily separable. Removal of the chiral sulfinyl group followed by structural manipulation afforded chiral gem -difluoromethylenated spiro-pyrrolidinyl and spiro-piperidinyl oxindoles.",10.1021/acs.joc.2c02098,2022-11-11,0.5887407231216125
Organic Letters,"Stereospecific Synthesis of 1,4,5,6-Tetrahydropyrimidines via Domino Ring-Opening Cyclization of Activated Aziridines with α-Acidic Isocyanides","An expeditious synthetic route to access structurally diverse 1,4,5,6-tetrahydropyrimidines via domino ring-opening cyclization of activated aziridines with α-acidic isocyanides has been established. The transformation proceeds via Lewis acid mediated S N 2-type ring opening of activated aziridines with α-carbanion of the isocyanides followed by a concomitant 6- endo - dig cyclization in a domino fashion to furnish the 1,4,5,6-tetrahydropyrimidine derivatives in excellent yields (up to 84%) and also in diastereo- and enantiomerically pure form (dr >99:1, ee >99%).",10.1021/acs.orglett.8b00986,2018-05-08,0.5887368961992191
Tetrahedron,Stereochemical control in the metallohalocarbenoid route to linear enediynes,,10.1016/s0040-4039(99)01593-2,1999-10-01,0.5887368815989461
Organic Process Research & Development,Development of a Commercial Process for (<i>S</i>)-β-Phenylalanine,"The development of a commercial manufacturing route for ( S )-β-phenylalanine 8, a key pharmaceutical building block, is described. The different approaches which were investigated, based on catalytic asymmetric hydrogenation of enamide intermediates and on biocatalysis using acylase and lipase hydrolyses, are compared. The lipase resolution route was chosen for scale-up, and the final two-step process, based on readily available raw materials, is shown to be robust at full manufacturing scale",10.1021/op200084g,2011-06-13,0.5887364658595506
Journal of Organic Chemistry,Total Synthesis of Pestalotioprolide G and Putative Structure of Pestalotioprolide H,A concise and convergent route for the stereoselective total synthesis of cytotoxic macrolides pestalotioprolides G and H has been developed for the first time. Intramolecular Heck coupling has been chosen to cyclize the 14-membered macrocycle. This synthetic study strongly suggests that the proposed structure of pestalotioprolide H may need to be corrected as the spectroscopic data on the synthesized molecule deviate from the values reported for the isolated natural product.,10.1021/acs.joc.7b01115,2017-06-22,0.588734430381329
European Journal of Organic Chemistry,Synthetic Studies toward Actinorhodin and γ‐Actinorhodin by using a Homo‐coupling Strategy: Synthesis of Hemiactinorhodin and Hemi‐γ‐actinorhodin,"Abstract A homo‐coupling strategy toward the synthesis of actinorhodin and γ‐actinorhodin has been explored. The monomeric unit was synthesized by employing an efficient combination of Dötz benzannulation and oxa‐Pictet–Spengler reactions. Attempts towards oxidative homo‐coupling of the pyranonaphthalene monomer intermediate to give dimer were unsuccessful. Later, monomer pyranonaphthalene was carried forward to complete the synthesis of hemiactinorhodin and hemi‐γ‐actinorhodin.",10.1002/ejoc.201500510,2015-06-18,0.5887296334690992
Organic Letters,Asymmetric Synthesis of the Oxygenated Polycyclic System of (+)-Harringtonolide,"A straightforward asymmetric synthesis of the cage oxygenated structure of (+)-harringtonolide has been accomplished for the first time. The key steps involved (i) a templated stereoselective IMDA reaction to build a highly functionalized cyclohexene ring D, (ii) functionalization of the cycloadduct, (iii) ring-closing metathesis providing the five-membered ring C, and finally (iv) a challenging one-step cascade cyclization of an epoxy-alcohol toward the target structure, whose mechanism was investigated.",10.1021/ol300133x,2012-02-17,0.5887252707925713
Journal of the American Chemical Society,Total Synthesis and Stereochemical Assignment of (−)-Ushikulide A,"We report the determination of the full stereostructure of (-)-ushikulide A (1), a spiroketal containing macrolide by total synthesis. Ushikulide A (1) was isolated from a culture broth of Streptomyces sp. IUK-102 and exhibits potent immunosuppressant activity (IC(50) = 70 nM). To embark upon an ushikulide A synthesis, a tentative assignment was made based on analogy to cytovaricin (2), a related macrolide isolated from a culture of Streptomyces diastatochromogenes whose full structure was previously established via synthesis and X-ray crystallography. This report delineates studies on several key steps, namely a direct aldol reaction catalyzed by the dinuclear zinc ProPhenol complex, a metal catalyzed spiroketalization, as well as application of an unprecedented asymmetric alkynylation of a simple saturated aldehyde with methyl propiolate to prepare the nucleophilic partner for a Marshall-Tamaru propargylation. These studies culminated in the first total synthesis and stereochemical assignment of (-)-ushikulide A and significantly extended the scope of the above-mentioned methodologies.",10.1021/ja906056v,2009-09-23,0.5887091797427381
Organic Letters,Asymmetric Total Synthesis of Four <i>Stemona</i> Alkaloids,"Asymmetric total syntheses of four Stemona alkaloids were accomplished, and among them, bisdehydrostemoninine A and stemoninine A were synthesized for the first time. Notably, these four alkaloids were divergently synthesized from a common tetracyclic intermediate, which was easily obtained from a known compound. Friedel–Crafts acylation was employed to introduce the key side chain at position C3 of Stemona alkaloids.",10.1021/acs.orglett.3c00349,2023-03-26,0.5887079500387579
Organic Letters,"Pd(II)-Catalyzed One-Pot, Three-Step Route for the Synthesis of Unsymmetrical Acridines","Unsymmetric acridines are synthesized via a one-pot amination/cyclization/aromatization reaction for the first time. With Pd(OAc)2-X-Phos as the catalyst, a series of unsymmetric acridines are obtained in moderate to excellent yields (up to 99% yield). Meanwhile, the diphenylamine intermediate could be isolated, which is evidence of the domino process.",10.1021/ol402596g,2013-10-23,0.5887068551559749
Synthesis,Simplistic Expedient and Practical Synthesis of (±)-α-Lipoic Acid,Synthesis of α-lipoic acid has been achieved by a simple sequence of reactions. The synthesis highlights the use of α-chloroesters in a Reformatsky reaction. The intermediate keto acid is an intermediate from which both isomers of lipoic acid can be prepared.,10.1055/s-2005-861867,2005-01-01,0.5887051159268385
Journal of the American Chemical Society,"Enantioselective Synthesis of Chiral 1,4-Dihydroquinolines via Iridium-Catalyzed Asymmetric Partial Hydrogenation of Quinolines","Chiral 1,4-dihydroquinolines are frequently found in natural products and pharmaceuticals, yet a generally useful route for their synthesis remains elusive. Here, we present an asymmetric partial hydrogenation strategy to access enantioenriched 1,4-dihydroquinolines from quinolines. Our strategy involves incorporating an ester group at position 3 of the quinoline ring, thereby enhancing the electronic deficiency and polarity of the C3–C4 double bond. Employing a chiral Ir-SpiroPAP catalyst facilitated the hydrogenation of a wide variety of 4-substituted 3-ethoxycarbonylquinolines, yielding chiral 1,4-dihydroquinolines in high yields (up to 95%) with exceptional enantioselectivity and efficiency (up to 99% ee and 1840 TONs). Noteworthy for its scalability and practicality, the method provides a robust avenue for the synthesis of valuable compounds such as 9-aryl aza-podophyllotoxins and melatonin MT 2 receptor modulators. Density functional theory calculations were performed to gain insights into the reaction mechanism and the origins of the enantioselectivity.",10.1021/jacs.4c13618,2025-02-05,0.5887034390346133
European Journal of Organic Chemistry,"A Simple Stereoselective Synthesis of Enantiopure 2-Substituted Pyrrolidines and Piperidines from Chiral (R)-Phenylglycinol-Derived Bicyclic 1,3-Oxazolidines","Chiral, nonracemic 2-substituted pyrrolidines and piperidines were prepared in high ee and moderate to good chemical yields in three steps from (R)-phenylglycinol and γ- or δ-chloroketones. The key step of the synthesis was the stereoselective reductive ring-opening of chiral bicyclic 1,3-oxazolidines prepared by condensation of (R)-phenylglycinol and the corresponding ketones.",10.1002/(sici)1099-0690(200005)2000:9<1719::aid-ejoc1719>3.0.co;2-r,2000-05-01,0.5886908443368073
Journal of the American Chemical Society,Colloidal Synthesis of Cu<sub>2</sub>SnSe<sub>3</sub> Tetrapod Nanocrystals,The formation of Cu2SnSe3 tetrapod nanocrystals is reported using a hot injection colloidal synthesis. The ternary copper chalcogenide nanocrystals nucleate with a cubic core with four short wurzite arms.,10.1021/ja403083p,2013-05-10,0.5886897591354764
Journal of the American Chemical Society,Total Synthesis of Marinomycins A−C and of Their Monomeric Counterparts Monomarinomycin A and <i>iso</i>-Monomarinomycin A,"Marinomycins A-C (1-3), and their monomeric analogues monomarinomycin A (m-1) and iso-monomarinomycin A (m-2), were synthesized by a convergent strategy from key building blocks ketophosphonate 5, aldehyde 6, and dienyl bromide carboxylic acid 7. The first attempt to construct marinomycin A [1, convertible to marinomycins B (2) and C (3) by light] by direct Suzuki-type dimerization/cyclization of boronic acid dienyl bromide 4 led to premature ring closure to afford, after global desilylation, monomarinomycin A (m-1) and iso-monomarinomycin A (m-2) in good yield and only small amounts (< or =2%) of the desired product. A subsequent stepwise approach based on Suzuki-type couplings improved considerably the overall yield of marinomycin A (1), and hence of marinomycins B (2) and C (3). Alternative direct dimerization approaches based on the Stille and Heck coupling reactions also led to monomarinomycins A (m-1 and m-2), but failed to deliver useful amounts of marinomycin A (1).",10.1021/ja068053p,2007-01-24,0.5886859606475402
Journal of the American Chemical Society,"Enantioselective Total Syntheses of 13,14,15-Isocrambescidin 800 and 13,14,15-Isocrambescidin 657","The first total syntheses of 13,14,15-isocrambescidin 800 ( 1 ) and 13,14,15-isocrambescidin 657 ( 2 ) were accomplished in convergent fashion. The central strategic step was tethered Biginelli condensation of guanidine aminal 14 and β-ketoester 15 to give 1-iminohexahydropyrrolo[1,2- c ]pyrimidine carboxylic ester 16 . This step united all the heavy atoms of the pentacyclic guanidine nucleus and set the critical trans C10−C13 stereorelationship. Acidic treatment of derivative 18 triggered tricyclization to generate pentacyclic guanidine 19b in high yield. After cleavage of the allyl ester, the derived acid underwent coordinated epimerization at C14 and C15 in the presence of triethylamine to form the pentacyclic isocrambescidin nucleus. The synthesis of 1 was achieved in 11% overall yield from amine 12 by a sequence involving five isolated intermediates. As detailed in the preceding account, 12 can be accessed from commercially available 3-butyn-1-ol in 30% overall yield by way of nine isolated and purified intermediates. Mosher derivatives were prepared from ( S )-(−)-α-methoxy-α-(trifluoromethyl)phenylacetic acid and natural 1, synthetic 1, and synthetic C43 epimer 31 . Analysis by 19 F NMR showed that the Mosher derivatives of natural and synthetic 1 were identical, thus establishing for the first time that the stereochemistry of 13,14,15-isocrambescidin 800 ( 1 ) at C43 is S . The mechanism of the tricyclization and epimerization steps is discussed, as are the relative energies of the 13,14,15-isocrambescidin, 13,15-epicrambescidin, and 13-epicrambescidin guanidine moieties.",10.1021/ja000235a,2000-05-01,0.5886845378017187
Synlett,Mercuric Triflate·(TMU)<sub>2</sub>Catalyzed Cyclization of a Propargylic Ketone into a Monosubstituted Furan,"Formation of a furan derivative was observed in the course of a synthetic approach towards a new carotenoid metabolite, starting from a propargylic ketone, in the presence of mercuric triflate-tetramethylurea complex.",10.1055/s-2005-922779,2005-12-20,0.5886805310024606
Synthesis,Total Synthesis of the Leucetta-Derived Alkaloid Calcaridine A,"A biomimetically guided total synthesis of the Leucetta-derived aminoimidazole alkaloid, calcaridine A, is described. The synthesis relies on position selective metalations of a 4,5-diiodo­imidazole derivative to provide a tetrasubstituted imidazole. Subjection of this polysubstituted imidazole derivative to oxidative rearrangement with a Davis oxaziridine provides the corresponding imidazolone core of calcaridine A.",10.1055/s-0029-1216929,2009-08-07,0.5886778969503846
Synlett,"First Total Synthesis of Dioncophylline B, a 7,6′-Coupled Naphthylisoquinoline Alkaloid","All articles of this category The total synthesis of dioncophylline B ( 2 ), a naphthylisoquinoline alkaloid with the rare 7,6′-coupling type and high antimalarial and fungicidal activities, is described. The key step of this convergent synthesis is the regioselective intermolecular biaryl coupling of its appropriately modified naphthalene and isoquinoline moieties, with MOM-functionalized oxygen substituents next to the coupling sites: The naphthalene moiety is activated by a directed ortho -metalation → stannylation procedure, while the isoquinoline part is metalated and then brominated ortho to the MOM-protected oxygen function, thus allowing a Stille coupling to connect the two parts. The work constitutes the first synthesis of any 7,6′-coupled naphthylisoquinoline alkaloid. dioncophylline B - naphthylisoquinoline alkaloids - total synthesis - cross coupling - directed ortho -metalation",10.1055/s-1999-2575,1999-02-01,0.5886753275124272
Angewandte Chemie International Edition,Structure and Total Synthesis of Lysobactin (Katanosin B),"Tackle-resistant bacteria: Determination of the 3D structure of the antibiotic lysobactin has led to its total synthesis and resulted in a high-yielding macrolactamization step. The minimal use of protecting groups allowed preorganization of the side chains to steer the cyclization. Thus, a new chemical route has been developed in the search for innovative antibiotic lead structures.",10.1002/anie.200604232,2007-01-09,0.5886706374129929
Journal of Organic Chemistry,Total Synthesis and Absolute Configuration Determination of (+)-Bruguierol C,The first total synthesis and absolute configuration of bruguierol C are reported. The key step involved the diastereoselective capture of an in situ generated oxocarbenium ion via an intramolecular Friedel-Crafts alkylation.,10.1021/jo071035l,2007-07-14,0.5886684304530998
Synlett,Intramolecular Diels-Alder Strategy in a Synthetic Approach to the Eleutherobin Core,"An attractive intermediate in the total synthesis of eleutherobin has been synthesised. The key step of this synthesis is an intramolecular Diels-Alder reaction, which leads to intermediate possessing rings A and C of the eleutherobin skeleton.",10.1055/s-2005-869830,2005-01-01,0.5886672773474744
European Journal of Organic Chemistry,Application of a One‐Pot Friedel–Crafts Alkylation/Michael Addition Methodology to the Asymmetric Synthesis of Ergoline Derivatives,"Herein, we report a short and facile stereoselective route to ergoline derivatives. The key steps are a one‐pot Friedel–Crafts alkylation/Michael addition sequence which, in the absence of chiral ligands, affords the trans‐trans ‐stereoisomer in 44 % yield as a racemate. Screening of a range of chiral bisoxazoline ligands allowed this sequence to proceed in 42–55 % yields (six examples), with up to 99 % ee . This approach allows for the first time, substitution at the C 4 ‐position and the introduction of 3 chiral centres in one pot. An interesting, base‐mediated conversion of the trans‐trans ‐stereoisomer to the cis‐cis ‐stereoisomer was discovered and both stereoisomers were characterized by X‐ray crystallography.",10.1002/ejoc.201701480,2017-10-24,0.5886667903213736
Organic Process Research & Development,"Development of a Kilogram-Scale Synthesis of <i>cis</i>-LC15-0133 Tartrate, a Potent Dipeptidyl Peptidase IV Inhibitor","(4 S )- N -Boc-4-fluoro- l -proline methyl ester ( 4 ) was prepared from the following sequence of reactions: esterification of trans -4-hydroxy- l -proline ( 2 ), Boc protection, and fluorination by DAST. Reaction of 4 with lithiated oxadiazole provided oxadiazolyl ketone 7 . Deprotection of the Boc group of 7 and subsequent coupling with bromoacetyl bromide gave bromide 9 . Coupling reaction of 9 with excess oxazolidine 16 provided coupled product 17 . Unexpectedly, the stereogenic center of 17 was completely epimerized to a virtually 1:1 mixture of cis - and trans - 17 at this stage. After the deprotection of the N,O -methylene acetal group of 17 using aqueous ammonium chloride, crystallization induced dynamic resolution (CIDR) of cis - and trans -mixture of LC15-0133 ( 1 ) in the course of tartrate salt formation provided cis -LC15-0133 ( 1a ) tartrate salt in 83% yield (>98% de).",10.1021/op800076r,2008-06-04,0.5886648531185219
Tetrahedron,One-pot four-component synthesis of 4-hydrazinothiazoles: novel scaffolds for drug discovery,,10.1016/j.tetlet.2014.08.033,2014-08-14,0.5886584379793257
Journal of the American Chemical Society,"Total Syntheses of Polycyclic Diterpenes Phomopsene, Methyl Phomopsenonate, and <i>iso</i>-Phomopsene via Reorganization of C–C Single Bonds","The first total syntheses of polycyclic diterpenes phomopsene ( 1 ), methyl phomopsenonate ( 2 ), and iso -phomopsene ( 3 ) have been accomplished through the unusual cascade reorganization of C–C single bonds. This approach features: (i) a synergistic Nazarov cyclization/double ring expansions in one-step, developed by authors, to rapid and stereospecific construction of the 5/5/5/5 tetraquinane scaffold bearing contiguous quaternary centers and (ii) a one-pot strategic ring expansion through Beckmann fragmentation/recombination to efficiently assemble the requisite 5/5/6/5 tetracyclic skeleton of the target molecules 1 – 3 . This work enables us to determine that the correct structure of iso -phomopsene is, in fact, the C7 epimer of the originally assigned structure. Finally, the absolute configurations of three target molecules were confirmed through enantioselective synthesis.",10.1021/jacs.3c07044,2023-08-22,0.5886548638682858
Synlett,"Synthesis of Azepino[4,5-b]indole Analogues via 7-endo-Selective Cyclization of Isocyanoacetates and Indole-1,2-alkynylaldehydes: An Approach towards the Chromoazepinone Core","Synthesis of azepino[4,5- b ]indole analogues via copper-catalyzed 7- endo -selective heteroannulation is reported. This strategy involves the Knoevenagel condensation of indole-1,2-alkynylaldehydes and isocyanoacetates, followed by copper-catalyzed 7- endo -selective annulation gives the product. This approach is applied towards the synthesis of the chromoazepinone core.",10.1055/s-0035-1560460,2015-09-01,0.5886526319158988
Journal of Organic Chemistry,"A Convenient New Route to Piperidines, Pyrrolizidines, Indolizidines, and Quinolizidines by Cyclization of Acetylenic Sulfones with β- and γ-Chloroamines. Enantioselective Total Synthesis of Indolizidines<b>(</b><b>−</b><b>)-167B</b>,<b>(</b><b>−</b><b>)-209D</b>,<b>(</b><b>−</b><b>)-209B</b>, and<b>(</b><b>−</b><b>)-207A</b>","The methyl esters of (L)-phenylalanine and (L)-methionine underwent conjugate additions via their free amino groups to 1-(p-toluenesulfonyl)hexyne, followed by intramolecular acylation of the corresponding enamide anions and tautomerization to afford 2-benzyl-5-n-butyl-3-hydroxy-4-(p-toluenesulfonyl)pyrrole and 5-n-butyl-3-hydroxy-2-(2-methylthioethyl)-4-(p-toluenesulfonyl)pyr role, respectively. The conjugate additions of a series of acyclic and cyclic secondary beta- and gamma-chloroamines to acetylenic sulfones proceeded similarly under mild conditions. The resulting adducts were deprotonated with LDA in THF at -78 degrees C, and the resulting sulfone-stabilized carbanions underwent intramolecular alkylation to afford cyclic enamine sulfones. Thus, acyclic gamma-chloroalkyl-benzylamines afforded the corresponding 2- or 2,6-disubstituted piperidines, while 2-(chloromethyl)pyrrolidines, 2-(2-chloroethyl)pyrrolidines, 2-(chloromethyl)piperidines, and 2-(2-chloroethyl)piperidines produced the corresponding 3-substituted pyrrolizidines, 5- or 3-substituted indolizidines, and 4-substituted quinolizidines, respectively. 8-Methyl-5-substituted indolizidines were also prepared from the appropriate methyl-substituted chloroamine precursor. Enantioselective syntheses were achieved by employing chiral chloroamines derived from amino acids or other enantiopure precursors. Further transformations of several of the products provided concise syntheses of four dendrobatid alkaloids. Thus, reduction of (8aS)-5-n-propyl-6-(p-toluenesulfonyl)-delta5,6-indolizidine with sodium cyanoborohydride in trifluoroacetic acid, followed by reductive desulfonylation, afforded (-)-indolizidine 167B. The corresponding 5-n-hexyl derivative similarly produced (-)-indolizidine 209D, while (-)-(8R, 8aS)-8-methyl-5-n-pentyl-6-(p-toluenesulfonyl)-delta5,6-indo lizidine furnished (-)-indolizidine 209B. Finally, the similar reduction and debenzylation of (-)-(8R,8aS)-5-(2-benzyloxyethyl)-8-methyl-6-(p-toluenesulfo nyl)-delta5,6-indolizidine produced the corresponding 5-hydroxyethyl indolizidine. This was subjected to chlorination of the alcohol group with thionyl chloride and substitution with a higher order allyl cuprate reagent to afford (-)-indolizidine 207A.",10.1021/jo000080p,2000-06-29,0.5886526317835704
Synthesis,A New Route to Dialkyl 1-(Trimethylsilyl)- and 1-(Trimethylstannyl)-alkanephosphonates,,10.1055/s-1982-29914,1982-01-01,0.5886474044209925
Organic Letters,Stereoselective Synthesis of a Novel Apio Analogue of Neplanocin A as Potential <i>S</i>-Adenosylhomocysteine Hydrolase Inhibitor,"A total synthesis of apio-neplanocin A, which combines properties of apio nucleoside and neplanocin A and is a potential inhibitor of S-adenosylhomocysteine hydrolase, was accomplished starting from D-ribose via stereoselective hydroxymethylation and RCM reaction. [reaction: see text]",10.1021/ol026624m,2002-09-11,0.5886440067486525
Tetrahedron,An expeditious multigram preparation of the marine protein kinase inhibitor debromohymenialdisine,,10.1016/j.tetlet.2003.10.074,2003-12-01,0.588643800887627
Angewandte Chemie International Edition,Synthetic Studies on Ciguatoxin: A Convergent Strategy for Construction of the F-M Ring Framework,"Exceptional neurotoxicity is associated with ciguatoxin. The ciguatoxin mimic 1, which contains the F–M framework of the natural product, has been prepared through a convergent synthesis. The two key steps were a Lewis acid mediated intramolecular reaction of a γ-alkoxyallylsilane with an acetal group and an SmI2-mediated intramolecular Reformatsky reaction that permitted construction of the annelated hexahydrooxonin ring system.",10.1002/(sici)1521-3773(19980420)37:7<965::aid-anie965>3.0.co;2-p,1998-04-20,0.5886425791569541
Journal of Organic Chemistry,"Stereoselective Synthesis of 4α-Hydroxy-8,12-Guaianolides from Santonin","Hydroxyester 2, easily obtained from santonin (1), has been transformed into 10 alpha-hydroxyguai-3-en-8,12-olide 6, a good intermediate for the synthesis of natural 8,12-guaianolides. Compound 6 was obtained from 2 by photochemical rearrangement of its acetyl derivative 7, stereoselective hydrogenation on Pd/C, reduction, regioselective elimination, hydrolysis, and lactonization. The synthesis of the natural guaianolides 3-5 was carried out in two sequences in which the regioselective elimination of a hydroxyl group at C10 with triflic anhydride or SOCl2 to afford, respectively, the endo or exo double bond on C10 and the regioselective opening of the C3-C4 alpha-epoxide were the key steps.",10.1021/jo991756n,2000-03-16,0.5886212586359163
Journal of Organic Chemistry,Domino Carbocationic Rearrangement of Aryl-2-(1-<i>N</i>-methyl/benzyl-3-indolyl)cyclopropyl Ketones:  A Serendipitous Route to 1<i>H</i>-Cyclopenta[<i>c</i>]carbazole Framework,"Aryl-2-(N-methyl/benzyl-3-indolyl)cyclopropyl ketones 2a-m are shown to undergo a novel unexpected domino carbocationic rearrangement in the presence of SnCl(4)/CH(3)NO(2) yielding 2-aroyl-3-aryl-1H-cyclopenta[c]carbazoles 3a-m in good yields. The possible mechanistic pathway for this interesting transformation involves a series of cascade events, (a) electrophilic ring opening of cyclopropyl ketone, (b) intermolecular enol capture of the resulting zwitterionic intermediate, (c) electrophilic dimerization of indole moieties to give tetrahydrocarbazole intermediate and its subsequent aromatization by elimination of an indole moiety and dehydrogenation, and (d) intramolecular aldol condensation of the side chain to give a cyclopentene ring. The overall transformation involves formation of three carbon-carbon bonds along with a fused benzene and a substituted cyclopentene ring in one-pot operation from simple indole precursors.",10.1021/jo025827l,2002-11-23,0.5886205687549012
Tetrahedron,Palladium-mediated intramolecular cyclization of substituted pentynoic acids. A new route to γ-arylidenebutyrolactones,,10.1016/0040-4039(96)00063-9,1996-02-01,0.5886196545221092
Organic Letters,Total Synthesis of (±)-Rhazinilam via Red-Light-Driven Zinc(II)porphyrin-Catalyzed Radical Cyclization of <i>N</i>-Substituted Pyrrole,"A red-light-driven radical cyclization strategy has been developed for the concise synthesis of (±)-rhazinilam. The transformation, catalyzed by [5,15-bis(pentafluorophenyl)-10,20-diphenylporphinato]zinc(II), enables the efficient formation of a tetrahydroindolizine core from an N -acyloxyphthalimide-substituted pyrrole, providing a key intermediate en route to the target alkaloid.",10.1021/acs.orglett.5c01681,2025-05-27,0.5886161204613497
Journal of the American Chemical Society,"Kinetic Resolution of Terminal Epoxides via Highly Regioselective and Enantioselective Ring Opening with TMSN<sub>3</sub>. An Efficient, Catalytic Route to 1,2-Amino Alcohols",,10.1021/ja961708+,1996-01-01,0.5886142764294588
Organic Letters,"(<i>Z</i>)- or (<i>E</i>)-Selective Hydrogenation of Potassium (3,3,3-Trifluoroprop-1-yn-1-yl)trifluoroborate: Route to Either Isomer of β-Trifluoromethylstyrenes","A Pd-catalyzed hydrogenation of potassium (3,3,3-trifluoroprop-1-yn-1-yl)trifluoroborate providing either the (Z)- or (E)-isomer of the vinylborate in >98% purity is described. The initially formed (Z)-isomer of the alkene is transformed to the (E)-isomer with time, irrespective of the catalyst used; coupling with bromo- and iodoarenes provides a variety of (Z)- or (E)-β-trifluoromethylstyrenes. Also, a safe synthesis of the alkynyltrifluoroborate from HFC-245fa and BF3·OEt2 has been described.",10.1021/acs.orglett.5b00235,2015-02-23,0.5886122329790667
Organic Letters,A General Strategy to Synthesize ADP-7-Azido-heptose and ADP-Azido-mannoses and Their Heptosyltransferase Binding Properties,"The multistep synthesis of a novel ADP-7-azido-7-deoxy- l - glycero -β- d - manno -heptopyranoside 2a and several analogues as heptosyltransferase ligands is described. The synthesis of the key intermediate heptoside-1-β-phosphate 3a involved a β-stereoselective phosphorylation of lactol 4 employing diallyl chlorophosphate as a phosphorylating reagent. Five deprotected nucleotide sugars were generated by this synthetic sequence and evaluated as heptosyltransferase substrates ( K M, k cat ).",10.1021/acs.orglett.1c00048,2021-02-23,0.5886075580788585
Journal of the American Chemical Society,Ruthenium-Catalyzed Enantioselective Alkylation of Sulfenamides: A General Approach for the Synthesis of Drug Relevant <i>S</i>-Methyl and <i>S</i>-Cyclopropyl Sulfoximines,"Sulfoximines are increasingly utilized in pharmaceuticals and agrochemicals with all sulfoximine clinical candidates incorporating either an S -methyl or an S -cyclopropyl substituent. Here, we report on a general and efficient sequence for the asymmetric synthesis of both of these sulfoximine substitution patterns. The asymmetric synthesis of sulfilimine intermediates by the first Ru-catalyzed enantioselective alkylation of sulfenamides enables the first examples of enantioselective S -alkylation with monosubstituted diazo compounds. The reaction proceeds at ≤1 mol % Ru-catalyst loading, and for tert -butyl diazoacetate, high yields and ≥98:2 er are achieved for an exceedingly broad range of sulfenamides, including with S -(hetero)aryl, -alkenyl, -methyl, -benzyl, -branched alkyl, and - tert -butyl substituents and for sterically and electronically diverse N -acyl groups. Sulfenamides derived from densely functionalized advanced drug intermediates also alkylated with 99:1 er. After oxidation of an N -pivaloyl S - tert -butyl acetate substituted sulfilimine to the corresponding sulfoximine, treatment with trifluoracetic acid in an aprotic solvent resulted in decarboxylation to the S -methyl N -pivaloyl sulfoximine, while aqueous HCl resulted in both decarboxylation and cleavage of the N -acyl group to give the S -methyl NH sulfoximine. Alternatively, sulfoximine alkylation with dibromoethane followed by acid-mediated decarboxylation provided the S -cyclopropyl sulfoximine. The efficient asymmetric synthesis of the preclinical candidate LTGO-33 and the formal asymmetric synthesis of the phase II clinical candidate ART0380 demonstrate the utility of the disclosed approach.",10.1021/jacs.5c03841,2025-04-28,0.5886034306744731
Journal of Organic Chemistry,"First Synthesis of Enantiopure 1,6-Difunctionalized Dodecahydrobenz[<i>f</i>]indenes","An enantiospecific route to the previously unreported 1,6-difunctionalized dodecahydrobenz[f]indene ring system is described. Optically pure Hajos-Parrish ketone is used as the building block for preparation of a 6-methyleneinden-5-ol. This allylic alcohol is then utilized in a Claisen rearrangement under Johnson's conditions to introduce a side chain that is further modified and cyclized to produce the benz[f]indene ring system.",10.1021/jo048561m,2005-01-13,0.5885975395280412
Tetrahedron,Synthesis of the 5-HT1D receptor agonist MK-0462 via a Pd-catalyzed coupling reaction,,10.1016/0040-4039(94)88204-5,1994-09-01,0.5885967906163844
Journal of the American Chemical Society,Total Synthesis of the Potent and Broad-Spectrum Antibiotics Amycolamicin and Kibdelomycin,"The complex and intriguing structures of the antibiotics amycolamicin and kibdelomycin are herein confirmed through total synthesis. Careful titration of the synthetic products reveals that kibdelomycin is the salt form of amycolamicin. This synthesis employs a highly convergent strategy, which provides a modular approach for further SAR studies of this class of antibiotics.",10.1021/jacs.1c11477,2021-12-08,0.5885922319814763
Organic Process Research & Development,The Development of Scalable and Efficient Methods for the Preparation of Dicyclopropylamine HCl Salt,"The unique chemical properties of dicyclopropylamine (DCPA) 1 render its synthesis a challenge for process chemists despite its structural simplicity. Chemical instability and high aqueous solubility further complicate the process for DCPA’s preparation, isolation, and purification. In this note we describe the development of three strategies for the synthesis of DCPA 1, all of which provide material with excellent purity profiles (>99 GC area %). Our final route provides significant improvements in terms of cost-efficiency, safety, scalability, and impurity content. Highlights of this strategy include two chemo-selective, Pd-catalyzed, deallylation reactions and an efficient reductive amination protocol. To circumvent the chemical instability of DCPA 1, an innovative isolation procedure was developed which reliably reduced the amount of Pd residue to less than 20 ppm. Following this protocol, impurities such as N -propylcyclopropyl-, mono- cyclopropyl-, and N -ethyl-cyclopropylamines ( 3, 4, and 17 ) were minimized to 0.06, not detectable, and 0.02%, respectively.",10.1021/op2000755,2011-05-13,0.5885849305736041
Journal of Organic Chemistry,Formation and Disproportionation of Xanthenols to Xanthenes and Xanthones and Their Use in Synthesis,"-mediated cyclization followed by a Cannizzaro reaction has been developed for the synthesis of various xanthene derivatives. The reaction proceeded smoothly to afford both xanthenes/xanthones or their sulfur derivatives and tolerated a wide range of electronically diverse substrates. Using this methodology, pranoprofen was synthesized in three steps in 59% overall yield from commercially available starting materials.",10.1021/acs.joc.0c02694,2021-01-05,0.5885825509574807
Organic Letters,Enantioselective Synthesis of the 5–6–7 Carbocyclic Core of the Gagunin Diterpenoids,"A catalytic enantioselective double allylic alkylation reaction has been employed in the synthesis of the core of the gagunin diterpenoids. Enantioenriched material was advanced in 11 steps to afford the core of the highly oxygenated target, which includes two all-carbon quaternary stereocenters.",10.1021/ol401514s,2013-06-26,0.588581242476898
Angewandte Chemie International Edition,Total Synthesis of Chatancin,"As an antagonist of the platelet activating factor, chatancin (1), which is isolated from a soft coral, is of potential therapeutic use. The first total synthesis [Eq. (1)] of this structurally unusual diterpene in racemic form is described along with the formal total syntheses of natural (+)-chatancin as well as unnatural (-)-chatancin.",10.1002/(sici)1521-3773(19980904)37:16<2226::aid-anie2226>3.0.co;2-h,1998-09-04,0.5885768030441784
Angewandte Chemie International Edition,Total Synthesis of Chatancin,"As an antagonist of the platelet activating factor, chatancin (1), which is isolated from a soft coral, is of potential therapeutic use. The first total synthesis [Eq. (1)] of this structurally unusual diterpene in racemic form is described along with the formal total syntheses of natural (+)-chatancin as well as unnatural (−)-chatancin.",10.1002/(sici)1521-3773(19980904)37:16<2226::aid-anie2226>3.3.co;2-8,1998-09-04,0.5885768030441784
Organic Letters,"Palladium-Catalyzed Decarboxylative [4 + 3] Cyclization of γ-Methylidene-δ-valerolactones with 1,1-Dicyanocyclopropanes","A palladium-catalyzed decarboxylative [4 + 3] cyclization of gamma-methylidene-delta-valerolactones with 1,1-dicyanocyclopropanes has been developed to produce cycloheptane derivatives in a convergent manner. This method can be applied to the synthesis of azepanes by reacting with aziridines, and their asymmetric variants have also been described. In addition, selective ring-expansion reactions can be achieved for certain gamma-methylidene-delta-valerolactones to give nondecarboxylated nine-membered lactones.",10.1021/ol902326s,2009-11-12,0.5885685916659232
Tetrahedron,Mercury(II)-mediated cyclisation of hydroperoxyalkylcyclopropanes: a new route to cyclic peroxides,,10.1016/0040-4039(91)80453-d,1991-11-01,0.5885685697840554
Journal of Organic Chemistry,Synthesis and Biological Evaluation of a Phosphonate Analog of the Natural Acetyl Cholinesterase Inhibitor Cyclophostin,"Two diastereomers of a phosphonate analog 6 of the AChE inhibitor cyclophostin were synthesized. The substitution reaction of phosphono allylic carbonate 10a with methyl acetoacetate gave the vinyl phosphonate 9a. Attempted hydrogenation/debenzylation gave an unexpected enolether lactone. Alternatively, selective hydrogenation, demethylation, cyclization and debenzylation gave the phosphonate analog of cyclophostin as a separable mixture of diastereomers 6. The trans phosphonate isomer was more active than the cis isomer against AChE from two sources.",10.1021/jo801453v,2008-09-27,0.5885662803379706
Tetrahedron,Stereo- and regio-selective formation of 2-oxazolone telomers as potential synthetic intermediates for aminosugars,,10.1016/s0040-4039(01)86774-5,1979-01-01,0.5885662754179988
Tetrahedron,"One-pot inversion of d -mannono-1,4-lactone for the practical synthesis of l -ribose",,10.1016/s0040-4039(03)00552-5,2003-03-25,0.5885600435717127
Tetrahedron,A green route for the synthesis of 2-substituted benzoxazole derivatives catalyzed by Al3+-exchanged K10 clay,,10.1016/j.tetlet.2013.09.039,2013-09-19,0.5885593336120943
Tetrahedron,A new synthesis of HMG-CoA reductase inhibitor NK-104 through hydrosilylation-cross coupling reaction,,10.1016/s0040-4039(00)61406-5,1993-12-01,0.5885546282981567
Organic Letters,Biomimetic Enantioselective Total Synthesis of (−)-Mycoleptodiscin A,"Biomimetic total synthesis of (-)-mycoleptodiscin A (1) was achieved starting from the enantiopure key intermediate, which was prepared by Friedel-Crafts reaction between 7-methoxyindole and chiral primary allylic alcohol. The crucial step in this synthesis was an intramolecular Friedel-Crafts reaction at C-4 of the indole derivative driven by the EDG/EWG within a compound that was rationally designed to prevent the cyclization reaction at the C-2 positon of indole, thereby successfully providing the complete carbon framework of 1. This intramolecular Friedel-Crafts reaction at C-4 of indole derivative could be applied for the synthesis of other C-4-substituted indole alkaloid natural products.",10.1021/acs.orglett.6b03292,2016-12-01,0.5885518064096736
Organic Letters,"Stereoelectronic versus Steric Tuning in the Prins Cyclization Reaction: Synthesis of 2,6-<i>trans</i> Pyranyl Motifs","The use of carboalkoxyl allenic alcohol for the efficient synthesis of pyranyl motifs via Prins cyclization is described. This method provides easy access to 2,6-trans dihydropyrans in good yield and high diastereoselectivity.",10.1021/ol900196w,2009-03-20,0.588549935818801
Tetrahedron,"Improved synthesis of (9Z)-9,13-tetradecadien-11-ynal, the sex pheromone of the avocado seed moth, Stenoma catenifer",,10.1016/j.tetlet.2010.01.010,2010-01-12,0.588542431851731
Synthesis,Synthesis of Prostaglandins III:<sup>1</sup>Efficient and Practical Synthesis of Antisecretory Prostaglandin Enprostil,All articles of this category An efficient and practical 8-step synthesis of enprostil ( 1 ) starting from the lactone 2 has been developed. The propargylic acetate 5 was prepared from the lactol 3 by the reaction with ethynylmagnesium bromide followed by acetylation. Propargylic acetate 5 was converted into enprostil ( 1 ) via the introduction of an allene moity by reaction with a Grignard reagent in the presence of a CuI · P(OEt) 3 complex.,10.1055/s-1994-25576,1994-01-01,0.5885421667485558
Tetrahedron,"A practical conversion of natural physostigmine into the potent butyrylcholinesterase inhibitor N1,N8-bisnorcymserine",,10.1016/s0040-4039(00)00740-1,2000-06-01,0.588540717714842
Organic Letters,Heterobifunctional Multivalent Inhibitor-Adaptor Mediates Specific Aggregation between Shiga Toxin and a Pentraxin,"[reaction: see text] The first example of a multivalent heterofunctional inhibitor-adaptor, called ""BAIT"", is described. This multivalent inhibitor-adaptor is able to capture a ""target"" receptor (Shiga toxin) through its recognition of one ligand of a heterobivalent headgroup while the other ligand binds to an endogenous ""trap"" protein (serum amyloid P component, SAP). BAIT showed markedly enhanced inhibition of toxin activity. An efficient synthesis of this multivalent cluster containing heterobifunctional ligands was accomplished by chemical and chemoenzymatic approaches.",10.1021/ol051529+,2005-09-01,0.5885386467322674
Organic Process Research & Development,"An Efficient Synthetic Process for Scale-Up Production of 4,5-Diamino-2-(trifluoromethyl)benzonitrile and 5-Bromo-3-(trifluoromethyl)benzene-1,2-diamine","Starting from 4-amino-2-(trifluoromethyl)benzonitrile ( 6 ), an efficient and nonchromatographic process was developed for multihundred gram production of 4,5-diamino-2-(trifluoromethyl)benzonitrile ( 1 ) in 73% yield and 98 HPLC area% purity over four synthetic steps. The same synthetic strategy was applied to 4-bromo-2-(trifluoromethyl)aniline ( 7 ) that afforded 5-bromo-3-(trifluoromethyl)benzene-1,2-diamine ( 5 ) in 81% overall yield and 99% HPLC area% purity.",10.1021/op9000498,2009-04-27,0.5885335753325996
Journal of Organic Chemistry,A Formal Total Synthesis of (±)-Neplanocin A,"Stereoselective formal synthesis of (+/-)-neplanocin A from a cyclopentane derivative employing an elegant strategy involving reiterative usage of an already existing acetonide protecting group is reported. The acetonide protecting group that is carried forward intact right from the starting adduct to an advanced intermediate is shuffled around twice as in a ""relay race"" through the synthetic sequence, thus avoiding unnecessary employment of additional protecting groups.",10.1021/jo0710127,2007-08-01,0.5885323413746176
Synthesis,"First Stereoselective Synthesis of the Versatile Chiral Building Block (7aR)-5,6-Dihydro-7a-methyl-1H-indene-2,7(4H,7aH)-dione","All articles of this category A versatile chiral building block (7a R )-5,6-dihydro-7a-methyl-1 H -indene-2,7(4 H ,7a H ) -dione ( 4 ) was firstly enantiomerically synthesized from the microbial transformation ketol product 6 in 61.3% overall yield and over 96% ee. asymmetric synthesis - microbial reduction - ketols - bicyclic compounds - Wieland-Miescher ketone analog",10.1055/s-2000-8196,2000-01-01,0.5885197366430941
Angewandte Chemie International Edition,A Palladium‐Catalyzed Aminoalkynylation Strategy towards Bicyclic Heterocycles: Synthesis of (±)‐Trachelanthamidine,"Sweet cyclizations: The synthesis of pyrrolizidines and indolizidines has been achieved. Olefins were subjected to an intramolecular palladium-catalyzed aminoalkynylation with the hypervalent iodine reagent TIPS-EBX. After removal of the protecting group, a two-step cyclization sequence and subsequent reduction led to the natural product (±)-trachelanthamidine (see scheme; TIPS-EBX=triisopropylsilyl ethynylbenziodoxolone).",10.1002/anie.201100718,2011-04-15,0.5885147566073696
Organic Letters,A 4 + 3 Cycloaddition Approach to the Synthesis of Spatol. A Formal Total Synthesis of Racemic Spatol,[reaction: see text] A formal total synthesis of racemic spatol is presented. The key steps involved a 4 + 3 cycloaddition of a halogenated cyclopentenyl cation to cyclopentadiene and a quasi-Favorskii rearrangement.,10.1021/ol016200c,2001-07-07,0.5885079816056639
Angewandte Chemie International Edition,Total Synthesis of the Polycyclic Fungal Metabolite (±)‐Communesin F,"What the Heck: The heptacyclic fungal alkaloid communesin F was the target of a total synthesis featuring a rare example of an intramolecular Heck cyclization of a tetrasubstituted alkene, a reductive cyclization of an N-Boc aniline, a stereoselective C allylation of a lactam, and an azide reduction/N-Boc-δ-lactam ring opening sequence (see scheme, BOM=benzyloxymethyl).",10.1002/anie.200906818,2010-02-19,0.5885014196423697
Journal of Organic Chemistry,"Practical Enantiospecific Synthesis of an Orthogonally Protected 1,4-<i>trans</i>-1,5-<i>cis</i>- 4,5-Diamino-2-cyclopenten-1-ol Derivative","An enantiospecific synthesis of an orthogonally protected 1,4-trans-1,5-cis-4,5-diamino-2-cyclopenten-1-ol derivative 16 is reported. The trans-diamine moiety was established by anti-specific vinyl addition to a novel threitol-derived tert-butanesulfinylimine 2 and Overman rearrangement. The cyclopentene skeleton was constructed via RCM reaction of a key 1,6-diene intermediate 11.",10.1021/jo1009118,2010-08-09,0.5885005220095981
Tetrahedron,"Mevinic acids and analogs : a novel efficient route to chiral synthons from 1,6-anhydro-D-glucose",,10.1016/s0040-4039(01)93842-0,1989-01-01,0.588500168573565
Journal of Organic Chemistry,"Syntheses of Strychnine, Norfluorocurarine, Dehydrodesacetylretuline, and Valparicine Enabled by Intramolecular Cycloadditions of Zincke Aldehydes","A full account of the development of the base-mediated intramolecular Diels-Alder cycloadditions of tryptamine-derived Zincke aldehydes is described. This important complexity-generating transformation provides the tetracyclic core of many indole monoterpene alkaloids in only three steps from commercially available starting materials and played a key role in short syntheses of norfluorocurarine (five steps), dehydrodesacetylretuline (six steps), valparicine (seven steps), and strychnine (six steps). Reasonable mechanistic possibilities for this reaction, a surprisingly facile dimerization of the products, and an unexpected cycloreversion to regenerate Zincke aldehydes under specific conditions are also discussed.",10.1021/jo2020246,2011-12-14,0.5885000521100668
Tetrahedron,"Route to pyrrolo[1,2-a]quinoxalines via a furan ring opening-pyrrole ring closure sequence",,10.1016/j.tetlet.2019.151532,2019-12-17,0.5885000487329107
Tetrahedron,A simplified route to the synthesis of new 99mTc-specific tetradentate ligands,,10.1016/s0040-4039(02)02385-7,2002-12-01,0.588494362193248
Journal of the American Chemical Society,Total Synthesis of Rubriflordilactone A,"The first and asymmetric total synthesis of rubriflordilactone A, a bisnortriterpenoid isolated from Schisandra rubriflora, has been accomplished in a convergent manner. Two enantioenriched fragments were forged together to give a functionalized cis-triene. A 6π-electrocyclization/aromatization sequence assembled the penta-substituted arene, and a formal vinylogous Mukaiyama aldol reaction introduced the butenolide side chain.",10.1021/ja5092563,2014-10-31,0.5884916101383214
Tetrahedron,"A new, fast and efficient synthesis of 3-aryl indenones: intramolecular cyclization of 1,3-diarylpropynones in superacids",,10.1016/j.tetlet.2004.03.026,2004-03-29,0.5884822029490162
Synthesis,A Synthesis of (+)-Herboxidiene A,"All articles of this category Key steps in a stereoselective synthesis of Herboxidiene A, a diastereoisomer of the natural herbicide Herboxidiene, include a Hoppe homoaldol reaction, a copper(I)-mediated 1,2-metallate rearrangement, and a one-pot synthesis of a diene fragment from condensation of a lithiated benzothiazolyl sulfone and an aldehyde. herbicide - 1,2-metallate rearrangement - organocuprate - homoaldol reaction - Julia olefination - directed epoxidation",10.1055/s-1996-4254,1996-05-01,0.5884742826862591
Organic Letters,"Divergent Enantioselective Total Synthesis of (−)-Ajmalicine, (+)-Mayumbine, and (−)-Roxburghine C","High Resolution Image Download MS PowerPoint Slide We report herein a divergent enantioselective total synthesis of (−)-ajmalicine, (+)-mayumbine, and (−)-roxburghine C. The synthesis employs Franzén’s organocatalytic reaction between N -acetoacetyl tryptamine and ( E )-5-hydroxypent-2-enal to generate a functionalized pentacyclic compound with high diastereo- and enantioselectivity. This intermediate serves as a versatile platform for accessing the three heteroyohimbine alkaloids. Notably, a diastereoselective intramolecular Pictet–Spengler reaction of methyl ketone and chemoselective reduction of β-amidoester to β-enaminoester were exploited for the synthesis of (−)-roxburghine C.",10.1021/acs.orglett.5c00715,2025-03-20,0.588461989604621
Journal of Organic Chemistry,An Expedient Synthesis of the Fibril Binding Compound FSB via Sequential Pd-Catalyzed Coupling Reactions,"The styryl benzene derivative (E, E)-1-fluoro-2,5-bis(3-hydroxycarbonyl-4-hydroxy)styrylbenzene (FSB), well-known for its binding to beta-amyloid peptide fibrils, was synthesized in an efficient manner exploiting two sequential palladium(0)-catalyzed coupling reactions in a 34% overall yield. This is a substantial improvement to the previously reported synthesis of FSB in 1.1%.",10.1021/jo7026189,2008-03-26,0.5884600061234571
Journal of Organic Chemistry,An Enantioselective Organocatalytic Approach to Both Enantiomers of Lasubine II,"A concise stereoselective route providing access to both enantiomers of the bioactive quinolizidine alkaloid lasubine II has been developed. The enantioselectivity was introduced by taking advantage of a proline-catalyzed asymmetric Mannich reaction. Next, the bicyclic system was constructed via a diastereoselective Mannich cyclization and subsequent ring-closing metathesis as the key steps.",10.1021/jo900141f,2009-03-13,0.5884517843962582
Synlett,"A Concise Enantioselective Synthesis of (+)-L-733,060 and (+)-T-2328 via Sequential Proline Catalysis","A new, sequential proline-catalyzed approach to the synthesis of (+)-L-733,060 and (+)-T-2328 in high optical purity (93% ee) is described starting from phenyl N -Boc imine. The strategy involves proline-catalyzed Mannich reaction of an arylimine with acetaldehyde followed by α-aminoxylation/Wittig olefination in a sequential fashion as the key steps.",10.1055/s-0035-1561346,2016-02-04,0.5884505410045977
Journal of Organic Chemistry,Diasteroselective Cyclizations with Enantiopure Malonaldehyde Monocycloacetals,"The synthesis of a series of enantiopure malonaldehyde monocycloacetals is described. Treatment of 8b with L-tryptophan methyl ester, 5-methoxytryptamine, and tryptamine, respectively, in the Pictet-Spengler condensation gave the corresponding enantiomerically pure key precursors 1-3 and 17-21 in only two steps. Using a chiral amino-diol successfully realized the kinetic resolution of racemic carbolines 23 and 24.",10.1021/jo0057351,2001-12-13,0.5884410685057587
Organic Letters,Studies toward the Synthesis of Maoecrystal V,An approach toward the synthesis of maoecrystal V is described. The synthetic strategy for this approach was designed to address unique challenges posed by the strained tetrahydrofuran ring at the center of the target structure.,10.1021/ol1031238,2011-01-27,0.5884361887218261
Organic Letters,"AgSCF<sub>3</sub>-Mediated Oxidative Trifluoromethythiolation of Alkynes with Dearomatization to Synthesize SCF<sub>3</sub>-Substituted Spiro[4,5]trienones","A new method for the AgSCF3-mediated radical cascade difunctionalizing trifluoromethythiolation of alkynes with dearomatization is developed. This protocol provides a novel route to SCF3-substituted spirocyclic compounds via the formation of one C-SCF3 bond, one C-C bond, and one C-O double bond in a single step.",10.1021/acs.orglett.6b01702,2016-06-29,0.588431332235656
Tetrahedron,Total synthesis of new porphyrins isolated from the coral sea demosponge corallistes sp.,,10.1016/0040-4039(94)88251-7,1994-10-01,0.5884260490938524
European Journal of Organic Chemistry,"Divergent Total Syntheses of 2, 6‐Dioxabicyclo[3.3.1]nonan‐3‐one Styryllactones: (−)‐Goniopypyrone, (+)‐Goniochelienlactone and (+)‐7‐Acetylgoniochelienlactone","Abstract Stereoselective total syntheses of (+)‐goniochelienlactone, (+)‐7‐acetylgoniochelienlactone and (−)‐goniopypyrone were accomplished by divergent strategies starting from readily available chiral pool methyl α ‐D‐mannopyranoside. The present work provided an efficient strategy for the stereoselective construction of highly functionalized dioxabicyclo[3.3.1]nonan‐3‐one ring system through a sequential Bernet‐Vasella‐type reductive elimination/nucleophilic addition and a sequential cross‐metathesis/intramolecular oxa‐Michael addition in a one‐pot process.",10.1002/ejoc.202300749,2023-09-22,0.5884252174742738
Synlett,A Novel Short-Step Synthesis of New Xanthenedione Derivatives from the Cyclization of 3-Cinnamoyl-2-styrylchromones,"Novel (E)-3-aryl-4-benzylidene-8-hydroxy-3,4-dihydro-1H-xanthene-1,9(2H)-diones are prepared by the cyclization of (E,E)-3-cinnamoyl-5-hydroxy-2-styrylchromones efficiently catalyzed with boron tribromide. The (E,E)-3-cinnamoyl-5-hydroxy-2styrylchromones are obtained from the Baker-Venkataraman rearrangement of (E,E)-2-acetyl-1,3-phenylene bis(3-phenylacrylate), which is greatly improved under microwave irradiation.",10.1055/s-0030-1261172,2011-08-10,0.588419382326163
Organic Process Research & Development,"Old is Gold? Nefopam Hydrochloride, a Non-opioid and Non-steroidal Analgesic Drug and Its Practical One-Pot Synthesis in a Single Solvent for Large-Scale Production","Nefopam hydrochloride is extensively used in most of the European countries until today as an analgesic because of its non-opiate (non-narcotic) and non-steroidal action with fewer side effects compared with opioid and other analgesics, which cause more troublesome side effects. A multikilogram synthesis of nefopam hydrochloride has been achieved in one pot using a single solvent (toluene). A ≥99.9% purity of the active pharmaceutical ingredient (API) was achieved in excellent overall yield (≥79%). The one-pot, five-step synthetic process involves formation of an acid chloride ( 3 ) from benzoylbenzoic acid ( 2 ) followed by amidation ( 4 ), reduction ( 5 ), cyclization ( 6 ), and formation of the hydrochloride salt ( 1 ). The major advantages include (i) use of a single solvent, (ii) >90% conversion in each step, (iii) a cost-effective and operationally friendly process, (iv) averting the formation of genotoxic impurities, and (v) improved overall yield (≥79%) provided by the one-pot operation. For the first time, we report the characterization data of API 1, intermediates 3, 4, and 5, and also a possible impurity ( 5a ).",10.1021/acs.oprd.7b00228,2017-10-19,0.5884108820812635
Synthesis,"Simple, Efficient and Convenient Synthesis of<i>O,S</i>-Diethyl Bromomethyl(methyl)thiomalonate","All articles of this category O,S -Diethyl bromomethyl(methyl)thiomalonate (3) has been prepared in a short, efficient synthesis from commercially available ethyl 2-cyanopropionate (1) .",10.1055/s-1993-25980,1993-01-01,0.5884059636127189
Synlett,The Total Synthesis of the Marine Antitumor Grossularine-2,All articles of this category The first total synthesis of the marine antitumor grossularine-2 has been achieved in nine step sequence. Grossularine-2 - total synthesis - electrocyclic reaction - 2-azahexatriene system,10.1055/s-1995-4910,1995-02-01,0.588402993323882
Journal of Organic Chemistry,Synthesis of a CDE Fragment of the Insect Antifeedant 12-Hydroxyazadiradione,"A diastereoselective and versatile synthesis of the model insect antifeedant 23 related to 12-hydroxyazadiradione has been achieved in 11 steps starting from α-cyclocitral, 1 . The key steps involve intramolecular 1,3-dipolar cycloaddition of a nitrile oxide and a Stille coupling reaction of a vinyl iodide with a stannylfuran.",10.1021/jo961100j,1996-01-01,0.5883954848024224
Journal of Organic Chemistry,Design and Synthesis of Lamellarin D Analogues Targeting Topoisomerase I,"A general synthetic route to rationally designed lamellarin D analogues, 1-dearyllamellarin D (1) and 1-substituted 1-dearyllamellarin D (2), has been developed. The key pentacyclic intermediate 22 was prepared by palladium-catalyzed direct arylation of 12, which in turn was synthesized via C-2-selective lithiation of 15 followed by palladium-catalyzed cross-coupling as the key reactions. Compound 22 was converted to a wide range of C-1-substituted analogues 2 via regioselective electrophilic substitution and palladium-catalyzed cross-coupling reactions.",10.1021/jo901589e,2009-09-30,0.5883911142424255
Tetrahedron,A simple route for the synthesis of 4-chlorochromenes and chroman-4-ones,,10.1016/0040-4039(88)85197-9,1988-01-01,0.5883864118409965
Tetrahedron,"Asymmetric syntheses of (1R,1′R,5′R,7′R) and (1S,1′R,5′R,7′R)-1-hydroxy-exo-brevicomin and a formal synthesis of (+)-exo-brevicomin",,10.1016/j.tetlet.2003.12.157,2004-01-30,0.5883792217357701
Journal of Organic Chemistry,The Synthesis of a Naloxone-Related Oxidative Drug Product Degradant,"High Resolution Image Download MS PowerPoint Slide Naloxone is a nonselective opioid receptor antagonist used to reverse the effects of opiate-related overdose. Studies aimed toward identifying naloxone degradants present in a buprenorphine/naloxone combination drug product revealed several compounds whose structures could not be confirmed by comparison to authentic samples. We report herein the confirmation of the structural assignment of one of these compounds (so-called, “Degradant E”) by chemical synthesis starting from naloxone. Key features of the developed route include the conversion of the N -allyl group to the corresponding Boc carbamate as a means of facilitating the chemoselective oxidative cleavage of the C6–C7 bond. In addition, the use of a pivalate ester derivative of naloxone’s phenol group offered a convenient means of isolating Degradant E as the corresponding HCl salt using an acid-promoted global ester hydrolysis in the final step.",10.1021/acs.joc.5c00313,2025-04-14,0.5883759179770292
Organic Letters,Formal Total Synthesis of (±)-Strictamine Based on a Gold-Catalyzed Cyclization,"A gold-catalyzed cyclization of 1-propargyl-1,2,3,4-tetrahydro-β-carboline led to formation the D-ring of strictamine. Functional group modifications of the resulting tetracyclic indolenine led to the formal total synthesis of (±)-strictamine.",10.1021/acs.orglett.6b00536,2016-03-24,0.5883562308807423
Journal of Organic Chemistry,"General Strategy for the Synthesis of B<sub>1</sub> and L<sub>1</sub> Prostanoids: Synthesis of Phytoprostanes (<i>RS</i>)-9-L<sub>1</sub>-PhytoP, (<i>R</i>)-9-L<sub>1</sub>-PhytoP, (<i>RS</i>)-16-B<sub>1</sub>-PhytoP, and (<i>RS</i>)-16-L<sub>1</sub>-PhytoP","In this paper we describe a novel general synthetic approach to B1- and L1-type phytoprostanes, which are formed in vivo from free-radical-catalyzed nonenzymatic peroxidation of α-linolenic acid (1). The synthesis of phytoprostanes (RS)-9-L1-PhytoP (5), (R)-9-L1-PhytoP (5a), (RS)-16-B1-PhytoP (6), and (RS)-16-L1-PhytoP (7) exemplifies this strategy. The common starting compound 8 has been proved to be synthetically equivalent to a cyclopent-2-en-1-one synthon having opposite donor and acceptor properties at carbons α and β, respectively. Key steps include the chemoselective lithiation of a 1-iodo-2-bromoolefin, the introduction of the side chains by transition-metal catalysis following Heck- or Suzuki-type protocols, the construction of an enone moiety by a mild Au(I)-catalyzed Meyer Schuster rearrangement, and a lipase-mediated hydrolysis of methyl esters to deliver the phytoprostanes as free carboxylic acids.",10.1021/jo502538b,2015-01-09,0.5883468598632746
Journal of Organic Chemistry,"Triple Benzannulation of Naphthalene via a 1,3,6-Naphthotriyne Synthetic Equivalent. Synthesis of Dibenz[<i>a</i>,<i>c</i>]anthracene","A new synthesis of dibenzo[a,c]anthracene (4) is described that features the generation, from tetrabromo-bis-triflate 1 and phenyllithium, of a 1,3,6-naphthotriyne (2) synthetic equivalent that is trapped with 3 equiv of furan to form Diels-Alder tris-adduct 3. A subsequent two-step deoxygenation of 3 represents the first synthesis of dibenz[a,c]anthracene (4) that involves a tandem aryne Diels-Alder cycloaddition-deoxygenation strategy.",10.1021/acs.joc.5b01972,2015-10-09,0.5883405762515584
Journal of Organic Chemistry,An Efficient Preparation of TIPS−Halofluoropropyne and Its Application to the Diastereoselective Synthesis of Propargylic Fluorohydrins,,10.1021/jo000243+,2000-05-18,0.5883402201045411
Angewandte Chemie International Edition,Total Synthesis of Sporolide B,"An ocean of discovery: The first total synthesis of the highly oxygenated, marine-derived, natural product sporolide B has been achieved through a convergent strategy. The key steps involve a ruthenium-catalyzed [2+2+2] cycloaddition to assemble the indene structural motif and a thermally induced Diels-Alder-type reaction to forge the macrocycle (see scheme).",10.1002/anie.200900264,2009-02-24,0.5883394176305954
Angewandte Chemie International Edition,Palladium‐Catalyzed Arylation of Carbasugars Enables the Discovery of Potent and Selective SGLT2 Inhibitors,"Selective inhibition of the transporter protein sodium-glucose cotransporter 2 (SGLT2) has emerged as a promising way to control blood glucose level in diabetes patients. Reported herein is a short and convergent synthetic route towards some small-molecule SGLT2 inhibitors by a chemo- and diastereospecific palladium-catalyzed arylation reaction. This synthetic strategy enabled the discovery of two highly selective and potent SGLT2 inhibitors, thereby paving the way towards the development of carbasugar SGLT2 inhibitors as potential antidiabetic/antitumor agents.",10.1002/anie.201608758,2016-10-04,0.5883285731546386
Organic Letters,Palladium-Catalyzed Decarboxylative Coupling of Allylic Alkynoates with Arynes,A novel and selective protocol for the synthesis of 1-allyl-2-ethynylbenzenes has been developed by palladium-catalyzed decarboxylative coupling of allylic alkynoates with arynes. This new route allows for both sp-sp(2) and sp(2)-sp(3) couplings of allylic alkynoates with arynes in one pot involving a decarboxylation process.,10.1021/ol900643r,2009-04-29,0.5883237785205233
Journal of Organic Chemistry,"Phorbasides A−E, Cytotoxic Chlorocyclopropane Macrolide Glycosides from the Marine Sponge <i>Phorbas</i> sp. CD Determination of <i>C</i>-Methyl Sugar Configurations","Five new cytotoxic macrolide glycosides phorbasides A-E (3-7), each possessing a macrolide ring appended to a rare ene-yne-trans-2-chlorocyclopropane, were isolated from the same Western Australian sponge (Phorbas sp.) that provided phorboxazoles A and B. The structures of 3-7 were solved by analysis of spectroscopic data including NMR, MS, and CD. A synthesis of methyl 2-O-methyl-alpha-L-evalose from L-rhamnose was completed and used for configurational assignment of the sugar residue in 3. Acid-catalyzed methanolysis of 3 followed by two-step derivatization of the liberated O-methyl glycoside gave a vicinal 4-O-naphthoyl/tertiary 3-N-(2-aminonaphthyl)carbamate derivative that exhibited exciton coupled CD identical with that of the derivative prepared from synthetic 1,2- O-dimethyl-alpha-L-evalose.",10.1021/jo702307t,2008-04-16,0.5883203602855561
European Journal of Organic Chemistry,Synthesis of the C38−C44 Segment of Altohyrtin A − With an Addendum on the Preparation of 8-Oxabicyclo[3.2.1]oct-6-en-3-one,"The densely funkctionalized C38−C44 segment F of altohyrtin A with its five contiguous stereogenic centers was prepared in 10 steps and in 28 % overall yield (two steps per stereogenic center), from 8-oxabicyclo[3.2.1]oct-6-en-3-one as a template. The preparation of the title compound 1, m.p. 38 °C, is described on a 0.5-M scale in a three-step-two-stage reaction from acetone and furan. The oxacycle was stored without change at room temperature.",10.1002/1099-0690(200006)2000:12<2195::aid-ejoc2195>3.0.co;2-c,2000-06-01,0.5883179576097941
Angewandte Chemie International Edition,Phenotypic Identification of a Novel Autophagy Inhibitor Chemotype Targeting Lipid Kinase VPS34,"Autophagy is a critical regulator of cellular homeostasis and metabolism. Interference with this process is considered a new approach for the treatment of disease, in particular cancer and neurological disorders. Therefore, novel small-molecule autophagy modulators are in high demand. We describe the discovery of autophinib, a potent autophagy inhibitor with a novel chemotype. Autophinib was identified by means of a phenotypic assay monitoring the formation of autophagy-induced puncta, indicating accumulation of the lipidated cytosolic protein LC3 on the autophagosomal membrane. Target identification and validation revealed that autophinib inhibits autophagy induced by starvation or rapamycin by targeting the lipid kinase VPS34.",10.1002/anie.201703738,2017-05-24,0.588310866097574
Organic Letters,Stereoselective Synthesis of Pseudopeptide Microbial Agent AI-77-B,"[structure: see text]. An efficient and highly stereoselective synthesis of the gastroprotective natural product AI-77-B is described. The stereocenters of the hydroxy amino acid moiety were generated by an ester-derived titanium-enolate-mediated syn-aldol reaction, a Curtius rearrangement, and application of Dondoni's aldehyde homologation. Condensation with the dihydroisocoumarin fragment and subsequent deprotecting transformations furnished optically active AI-77-B.",10.1021/ol0101279,2001-08-01,0.5883041563819847
Synlett,A Short Synthesis of Methylenomycin B by the Nazarov Reaction,"All articles of this category Methylenomycin B was synthesized by the Nazarov reaction as a key step. The present synthesis was achieved in three steps from dimethyl methylphosphonate and involves two tandem reactions, which effectively shortened the synthetic path.",10.1055/s-1993-22417,1993-01-01,0.5882963439383732
Synthesis,The Catalytic Alkylative Desymmetrization of Anhydrides in a Formal Synthesis of Ionomycin,"The catalytic desymmetrization of anhydrides with zinc reagents provides access to deoxypolypropionate and polypropionate synthons. A synthesis of ionomycin was pursued in which three of the four fragments were assembled using this methodology. Two of the strategies (enol silane/oxocarbenium coupling and reductive cyclization) were not successful at installing the C23 stereocenter, but this stereochemical issue was overcome through a reduction/SN2 approach. In addition to the synthesis of a protected diastereomer of ionomycin, the synthesis of a C17–C32 fragment constitutes a formal total synthesis.",10.1055/s-0037-1610108,2018-05-29,0.5882919860687117
Organic Letters,New Synthesis of (±)-Isonucleosides,"[Structure: see text] A novel method for synthesizing isonucleosides, a new class of anti-HIV nucleosides, is described. 2,2-Dimethyl-1,3-dioxan-5-one was converted into a dioxabicyclohexane derivative in six steps. After cleaving the epoxide group with thiophenol, the resulting product was subjected to the Mitsunobu reaction in the presence of a nucleobase to give the desired isonucleoside derivative via migration of the thiophenyl group. Removal of the thiophenyl group under radical conditions followed by deprotection led to the 4'-substituted 2',3'-dideoxyisonucleosides as a racemic mixture.",10.1021/ol062491j,2006-11-18,0.5882907180337024
Journal of Organic Chemistry,Samarium(II) Iodide (SmI<sub>2</sub>)-Mediated Reductive Ring-Opening of Cyclopropanecarboxylates for Site-Selective Deuteration,"Herein, we report a SmI 2 -mediated reductive ring-opening deuteration of cyclopropanes bearing carboxylate ester substituents. This method enables the regioselective synthesis of α,γ-dideuterated esters with high deuterium incorporation efficiency. By increasing the stoichiometry of SmI 2 /Et 3 N/D 2 O, the reaction proceeds through a sequential pathway: initial cyclopropane ring-opening followed by ester reduction, yielding α,α,β,δ-tetradeuterated alcohols as the final products. Remarkably, near-quantitative deuterium labeling (>99% D) was achieved in all cases. Furthermore, the strategy was extended to carboxylic acid and amide-substituted cyclopropanes, demonstrating its broad applicability for accessing diverse deuterated molecules. This work significantly expands the toolbox for deuterium-labeled compound synthesis, particularly offering a novel route to tetradeuterated alcohols.",10.1021/acs.joc.5c00973,2025-08-08,0.5882901923772432
Journal of Organic Chemistry,"Asymmetric Induction via an Intramolecular Haloetherification Reaction of Chiral Ene Acetals:  A Novel Approach to Optically Active 1,4- and 1,5-Diols","An asymmetric synthesis of chiral 1,4- and 1,5-diols has been developed from the ene acetals 1a and 1c, prepared from the corresponding aldehydes and chiral C(2)-symmetric diols, involving remote asymmetric induction as a key step. In the first step, treatment of 1 with I(coll)(2)ClO(4) in the presence of an alcohol afforded the macrocyclic acetals (3-5 and 7) in a highly stereoselective manner. Subsequent nucleophilic substitution of iodide followed by a Grignard reaction with complete retention of stereochemistry and a final deprotection of the diphenylethylene or diphenylpropylene unit successfully gave optically active 1,4- and 1,5-diols in good yields.",10.1021/jo960714l,1996-01-01,0.5882870331335476
Tetrahedron,"Structure of discadenine, a spore germination inhibitor from the cellular slime mold,",,10.1016/s0040-4039(00)93115-0,1976-10-01,0.5882814827323176
Tetrahedron,Structure of syzygiol: a skin-tumor promotion inhibitor,,10.1016/0040-4039(91)80857-3,1991-01-01,0.5882814827323176
Organic Letters,"Asymmetric Synthesis of α-Amino 1,3-Dithioketals from Sulfinimines (<i>N</i>-Sulfinyl Imines). Synthesis of (2<i>S</i>,3<i>R</i>)-(−)-3-Hydroxy-3-methylproline","[reaction: see text] N-Sulfinyl alpha-amino 1,3-dithioketals are prepared in high de and good yield by treating sulfinimines with lithio-1,3-dithianes. Selective removal of the N-sulfinyl or the thioketal groups affords stable alpha-amino 1,3-dithioketals and N-sulfinyl alpha-amino ketones, respectively. This new sulfinimine-derived chiral building block is employed in the asymmetric synthesis of polyoxypeptin amino acid (2S,3R)-(-)-3-hydroxy-3-methylproline.",10.1021/ol0485971,2004-08-14,0.5882783869443787
Tetrahedron,"1,3- and 1,4- shifts of a methyl, group during fischer indole synthesis",,10.1016/s0040-4039(00)91448-5,1975-01-01,0.5882687720512585
Journal of the American Chemical Society,Chemoenzymatic Synthesis of Cryptophycin Anticancer Agents by an Ester Bond-Forming Non-ribosomal Peptide Synthetase Module,"Cryptophycins (Crp) are a group of cyanobacterial depsipeptides with activity against drug-resistant tumors. Although they have been shown to be promising, further efforts are required to return these highly potent compounds to the clinic through a new generation of analogues with improved medicinal properties. Herein, we report a chemosynthetic route relying on the multifunctional enzyme CrpD-M2 that incorporates a 2-hydroxy acid moiety (unit D) into Crp analogues. CrpD-M2 is a unique non-ribosomal peptide synthetase (NRPS) module comprised of condensation-adenylation-ketoreduction-thiolation (C-A-KR-T) domains. We interrogated A-domain 2-keto and 2-hydroxy acid activation and loading, and KR domain activity in the presence of NADPH and NADH. The resulting 2-hydroxy acid was elongated with three synthetic Crp chain elongation intermediate analogues through ester bond formation catalyzed by CrpD-M2 C domain. Finally, the enzyme-bound seco-Crp products were macrolactonized by the Crp thioesterase. Analysis of these sequential steps was enabled through LC-FTICR-MS of enzyme-bound intermediates and products. This novel chemoenzymatic synthesis of Crp involves four sequential catalytic steps leading to the incorporation of a 2-hydroxy acid moiety in the final chain elongation intermediate. The presented work constitutes the first example where a NRPS-embedded KR domain is employed for assembly of a fully elaborated natural product, and serves as a proof-of-principle for chemoenzymatic synthesis of new Crp analogues.",10.1021/ja204716f,2011-08-08,0.5882629487892419
Journal of Organic Chemistry,"C−H Insertion Approach to the Synthesis of <i>e</i><i>ndo,</i><i>e</i><i>xo</i>-Furofuranones:  Synthesis of (±)-Asarinin, (±)-Epimagnolin A, and (±)-Fargesin","A series of novel 5-aryl-4-aryloxymethyl-3-diazotetrahydrofuran-2-ones (12, 24, and 35a/b) have been prepared and found to undergo regio- and stereoselective C-H insertion reactions to afford 2,6-diaryl-3,7-dioxabicyclo[3.3.0]octane-8-ones (18, 26, and 36a/b) with endo,exo stereochemistry. Subsequent reduction of the lactone ring and cyclization of the resulting diols 27 and 37a/b permitted the synthesis of three endo,exo-furofuran lignans: asarinin (2), fargesin (3), and epimagnolin A (4). En route to the key diazo compounds 24 and 35a/b, a modified procedure for the Ghosez keteniminium-olefin cyclization was developed, which was required to minimize the decomposition of acid-sensitive functional groups such as electron-rich benzylic ethers that were present in the target compounds 2-4.",10.1021/jo015829q,2001-09-05,0.5882626285132514
Organic Letters,Palladium-Catalyzed Insertion of CO<sub>2</sub> into Vinylaziridines: New Route to 5-Vinyloxazolidinones,2-Vinylaziridines undergo a mild Pd-catalyzed ring-opening cyclization reaction with an ambient atmosphere of carbon dioxide to give 5-vinyloxazolidinones. The process is high yielding as well as regio- and stereoselective.,10.1021/ol201193d,2011-06-06,0.5882619410674867
Tetrahedron,Practical enantiospecific synthesis of RPR 111905: A novel non-peptide substance P antagonist,,10.1016/s0040-4039(96)02017-5,1996-11-01,0.5882583412949642
Angewandte Chemie International Edition,Terpenoid Synthesis via Convergent Radical Annulation,"The development of a convergent radical annulation strategy for the synthesis of complex terpenoids from sclareolide is disclosed. This approach employs a 1,3-diradical synthon to enable rapid C-ring annulation through inter- and intramolecular radical couplings, exemplified in the concise syntheses of serratene and cyclodammarane scaffolds from a common intermediate. Key features include a rapid alternating polarity (rAP) Kolbe electrolysis for onoceradiene assembly, a Co-electrocatalytic metal-catalyzed hydrogen atom transfer (MHAT) 7-endo-trig cycloisomerization─the first of its kind─to form the serratene core, and a tandem Fe-mediated reductive olefin coupling/enolate alkylation cascade─also unprecedented─to forge the [4.3.1] propellane motif of cyclodammaranes with complete diastereocontrol over three contiguous quaternary centers. These routes, completed in 5-9 steps, maximize skeletal bond-forming efficiency, feature unique radical cascades, and highlight the advantages of radical-based disconnections in terpenoid synthesis.",10.1002/anie.202521852,2025-11-24,0.5882580145527444
Journal of Organic Chemistry,Preparation of the 5/5-Spiroketal of the Ritterazines,The enantiomerically pure 5/5-spiroketal required for the synthesis of the ritterazines has been prepared with high diastereocontrol by ring closure followed by equilibration.,10.1021/jo0626461,2007-03-31,0.5882352168947811
Angewandte Chemie International Edition,Convergent Asymmetric Synthesis of (+)‐Aureothin Employing an Oxygenase‐Mediated Resolution Step,"Need an enzymatic push? The desymmetrization of α,α′-dimethoxy-γ-pyrone allows the convergent and rapid preparation of the complete carbon skeleton of (+)-aureothin (see scheme). The final step in the synthesis of the target molecule is the regiodivergent parallel kinetic resolution promoted by cytochrome P450 monooxygenase AurH to deliver the enantiopure natural product.",10.1002/anie.201204259,2012-07-16,0.5882351794650269
Journal of Organic Chemistry,Enantiospecific Synthesis of (−)-Slaframine and Related Hydroxylated Indolizidines. Utilization of a Nucleophilic Alaninol Synthon Derived from Serine<sup>1</sup>,"A general methodology for the synthesis of indolizidine alkaloids δ-coniceine ( 12 ), 1-hydroxyindolizidine ( 20 ), desacetoxy slaframine ( 24 ), slaframine ( 34 ), and an analogue ( 37 ) has been developed. This convergent approach utilizes the available chirality in proline and serine and is conceptually different from other approaches. A highly stereoselective coupling of the prolinals with a nucleophilic alaninol synthon provides the precursors for the key cyclization. A novel thermolytic annulation of an oxazolidinone is the key step in the formation of the six-membered piperidine ring. Further elaboration provides the target natural products 24, 34, and 37 in good overall yields.",10.1021/jo9908546,1999-08-01,0.5882263784949426
Journal of Organic Chemistry,A Novel Synthetic Route to Chiral γ-Lactams from α-Amino Acids via Rh-Catalyzed Intramolecular C−H Insertion,"Highly functionalized gamma-lactams are key intermediates for the synthesis of numerous biologically significant natural products. We herein described the synthesis of various chiral gamma-lactams via intramolecular C-H insertion of alpha-diazo-alpha-(phenylsulfonyl)acetamides derived from alpha-amino acids, which possess various functional groups. The cyclizations were highly regio- and stereoselective to afford chiral gamma-lactam motifs in high yields.",10.1021/jo0259717,2002-08-15,0.5882252189810958
Journal of Organic Chemistry,Total Synthesis of Lycopladine A and Carinatine A via a Base-Mediated Carbocyclization,"A concise, enantioselective synthesis of lycopladine A and carinatine A is presented. Our synthetic approach hinges on the recently developed mild carbocyclization of ynones to furnish the hydrindane core of the alkaloids. Their pyridine ring was efficiently installed using the Ciufolini method. Both heterocycles of carinatine A, a rare naturally occurring nitrone, were formed in a single operation.",10.1021/acs.joc.7b00908,2017-07-03,0.5882241389652847
Journal of the American Chemical Society,Total Synthesis of Terpenoids Employing a “Benzannulation of Carvone” Strategy: Synthesis of (−)-Crotogoudin,"Carvone is a sustainable and readily available starting material for organic synthesis. Herein, we present the syntheses of various natural product scaffolds that rely on a novel benzannulation involving the α-methyl group (C-10) of carvone to afford a versatile tetralin. The utility of our synthetic approach is highlighted by its application to a short synthesis of the ent-3,4-seco-atisane diterpenoid (-)-crotogoudin. The 13-step enantiospecific synthesis features a regioselective double oxidative dearomatization, a Diels-Alder cycloaddition with ethylene gas (to construct the bicyclo[2.2.2]octane framework), and a final acid-mediated lactonization. The versatility of this benzannulation strategy is demonstrated by its utility in the preparation of the carbon skeleton of ent-3,4-seco-abietane diterpenoids using an intramolecular oxidative dearomatization.",10.1021/jacs.7b06823,2017-08-01,0.5882238432295532
Synthesis,"Design, Synthesis and Structure-Odor Correlation of Novel Spiro[4.5]-decan-2-ones","Dehydration and Rupe rearrangement of 2-(3,3-dimethylcyclohexyl)hex-3-yne-2,5-diol (9) furnished as a 3% byproduct the intense vetiver-like smelling 4,7,7-trimethyl-1-methylene­spiro[4.5]decan-2-one (11). Motivated by the commercial importance of vetiver oil and the lack of synthetic substitutes as well as the lack of insight into the structural requirements for vetiver odorants, an efficient synthetic route to vetiver-like smelling compounds was developed. It consists of Wittig-Horner-Emmons reaction of diverse cycloalkanones with triethyl 2-phosphonopropionate, subsequent Grignard reaction with in situ conversion to the trienolate, and classical Nazarov cyclization of the resulting dienones. This route not only leads to 11 in 61% yield in the final Nazarov cyclization, but also to 16 analogs, which provide insight into both, the Nazarov reaction and the structure-odor relationship of vetiver odorants. Other vetiver-like smelling compounds discovered include (1RS,4SR,5SR)-1,4,7,7-tetramethylspiro[4.5]decan-2-one (16), 4-methyl-1-methylenespiro[4.6]undecan-2-one (30) and 4-methyl-1-methylenespiro[4.7]dodecan-2-one (31).",10.1055/s-2002-34847,2002-01-01,0.5882187245654367
Angewandte Chemie International Edition,β‐Lactam Synthesis through Diodomethane Addition to Amide Dianions,"We present a novel route for the quick and easy synthesis of a broad range of β-lactams. The synthesis involves a [3+1] cyclization of amide dianions with diiodomethane. In contrast to the seminal work of Hirai et al. from 1979, the reaction proved to be a general and efficient approach towards azetidinones. The ease of the process was confirmed by DFT calculations and its power demonstrated by a diversity-oriented synthesis of β-lactams with four points of diversity determined by the choice of Ugi adducts as starting materials.",10.1002/anie.201706315,2017-07-25,0.5882133573718608
Journal of the American Chemical Society,Total Synthesis of (+)-Epoxydictymene. Application of Alkoxy-Directed Cyclization to Diterpenoid Construction,"An enantioselective synthesis of (+)-epoxydictymene ( 1 ) is reported. Condensation of the enantiopure aldehydo ester 5 with ( S )-3-isopropylcyclopentenyllithium proceeds selectively to afford 13 . Once this lactone was methylenated with the Tebbe reagent, the newly formed allyl vinyl ether was induced into Claisen rearrangement under catalysis with triisobutylaluminum. Sequential hydroboration−oxidation of the resulting dicyclopentacyclooctenone derivative was followed by angular methylation and deoxygenation of the carbonyl functionality. Following epimerization at C-11, an α-hydroxyl was introduced regio- and stereoselectively. Some functional group manipulation led to 57 and 58, both of which underwent efficient cyclization to deliver the complete framework of the target molecule when irradiated with visible light in cyclohexane solution containing iodosobenzene diacetate and iodine. The generality of this key reaction, which efficiently constructs the strained oxabicyclo[3.3.0]octane subunit of 1, is demonstrated. This significant development permitted the conversion of 57 to 1 in two additional steps.",10.1021/ja971526v,1997-09-01,0.588205854181163
European Journal of Organic Chemistry,Synthesis of Substituted Coumarins and 2‐Quinolinones by Cycloisomerisation of (Hydroxy/aminophenyl)propargyl Alcohols,"Abstract A new cycloisomerization strategy for the synthesis of coumarins and quinolinones is described. The addition of ethoxyacetylide to 2‐hydroxyacetophenones directly resulted in 4‐substituted coumarins by 6‐ endo ‐ dig cycloisomerisation of the intermediate 3‐ethoxy‐1‐(2‐hydroxyphenyl)‐2‐propyn‐1‐ols. Under similar conditions, 2‐aminoacetophenone produced 2‐ethoxyquinoline, a masked quinolinone, which was converted into the quinolinone by acid treatment. N ‐Protected intermediate 8 was isolated and converted into the quinolinone [with In(OTf) 3 or H 2 SO 4 ] or the 3‐iodo‐2‐quinolinone (with I 2 and H + ).",10.1002/ejoc.201200782,2012-08-30,0.5882027791048263
Chemical Science,AlphaFold accelerates artificial intelligence powered drug discovery: efficient discovery of a novel CDK20 small molecule inhibitor,A novel CDK20 small molecule inhibitor discovered by artificial intelligence based on an AlphaFold-predicted structure demonstrates the first application of AlphaFold in hit identification for efficient drug discovery.,10.1039/d2sc05709c,2023-01-01,0.5882011909209273
Tetrahedron,"Synthesis of novel isoxazole-benzoquinone hybrids via 1,3-dipolar cycloaddition reaction as key step",,10.1016/j.tetlet.2012.05.123,2012-06-01,0.5882006680285007
Tetrahedron,Use of iodobenzene diacetate for the synthesis of α-iodoepoxides,,10.1016/0040-4039(91)80515-8,1991-12-01,0.5881996506143261
Tetrahedron,4′-Nitroarenesulphenanilides: Their use in the synthesis of unsymmetrical disulphides,,10.1016/s0040-4039(00)84361-0,1986-01-01,0.5881996506143261
Tetrahedron,Perspectives on the synthesis and use of ageladine A,,10.1016/j.tetlet.2015.05.081,2015-05-29,0.5881996506143261
Tetrahedron,Use of dilithio-tosylmethyl isocyanide in the synthesis of oxazoles and imidazoles,,10.1016/s0040-4039(00)78757-0,1980-01-01,0.5881996506143261
Tetrahedron,The use of phosphonodithioformates for the synthesis of ketene dithioacetals,,10.1016/s0040-4039(00)99259-1,1989-01-01,0.5881996506143261
Synlett,A Practical and Facile Approach towards Indole Alkaloids: (-)-Mitralactonine,An efficient approach to (-)-mitralactonine using Pictet-Spengler cyclisation with a highly functionalised masked aldehyde is described. Sharpless asymmetric dihydroxylation (SAD) is ­utilised to introduce chirality in the key substrate.,10.1055/s-2006-958434,2006-12-20,0.5881992298883482
Angewandte Chemie International Edition,A Double Allylation Strategy for Gram‐Scale Guaianolide Production: Total Synthesis of (+)‐Mikanokryptin,"With over 5000 members isolated to date, sesquiterpene lactones represent a prolific source of medicinal agents with several derivatives in human clinical trials. The guaianolides, a major subset of this group, have been intensely investigated from both medicinal and chemical-synthesis perspectives for decades. To date, the myriad stereochemical permutations presented by this enormous family have precluded the synthesis of many unique members. Herein we report the total synthesis of the trans-fused 8,12-guaianolide (+)-mikanokryptin in 10 steps from (+)-carvone. Notably, this synthesis is the first gram-scale total synthesis of a guaianolide natural product.",10.1002/anie.201611078,2017-01-03,0.5881962171921011
Organic Process Research & Development,Optimization of an Aminothiazine Ring Formation: Integrating Modeling with Experiments to Maximize Yield by Minimizing Impurity Formation,"The aminothiazine formation step is a key transformation in the process to synthesize a potent and selective inhibitor of Beta-Amyloid Cleaving Enzyme (BACE). There are several impurities formed during the telescoped process that impacted the overall yield of the transformation. In order to improve the overall yield and design the impurity control strategy, a mechanistic model was developed to understand the impact of different process parameters on yield and impurity levels. This work describes how mechanistic models were integrated with experiments to determine process conditions to maximize the yield by minimizing impurity formation.",10.1021/acs.oprd.5b00036,2015-08-03,0.5881948902822264
Synlett,Conformationally Locked Carbocyclic Nucleosides: Synthesis of the 1-Methyl-6-oxabicyclo[3.1.0]hexane Scaffold,"This paper describes the racemic and stereoselective ­synthesis of novel conformationally locked 3′-methyl-2′,3′-oxirane-fused carbocyclic nucleosides (nucleosides numbering). The key step is the direct coupling of an alcohol bearing the 1-methyl-6-oxa­bicyclo[3.1.0]hexane scaffold with diversely substituted purine ­nucleobases under Mitsunobu reaction conditions providing only the N9 target molecules.",10.1055/s-2006-949635,2006-09-01,0.5881928832707248
Organic Letters,Copper-Catalyzed C–O Bond Formation: An Efficient One-Pot Highly Regioselective Synthesis of Furans from (2-Furyl)Carbene Complexes,A convenient one-pot Cu(I)-catalyzed strategy for regioselective synthesis of trisubstituted furan derivatives has been developed via (2-furyl) carbene complexes. This process has opened a new synthetic route to a variety of α-carbonyl furans using air as the oxidant affording furans in good yields.,10.1021/ol400080e,2013-02-15,0.5881928267194961
Organic Letters,"Expedient Synthesis of Chiral Homoallylamines via <i>N</i>,<i>O</i>-Acetal TMS Ethers and Its Application","A highly stereoselective and efficient method for the synthesis of optically active homoallylamines was developed. Key features of the method include (1) the utilization of naphthylethylamine as both an excellent chiral auxiliary and the amine source, (2) the 1,3-chiral induction of the N-acyliminium ion with high stereoselectivity and high yield, and (3) facile auxiliary removal under mild conditions to liberate N-Cbz-protected homoallylamines. In addition, the total synthesis of the proposed novel tripeptide containing a β-amino acid has been achieved by applying this method.",10.1021/ol202573s,2011-10-13,0.5881926946185355
Journal of Organic Chemistry,Synthesis of a D-Ring Isomer of Galanthamine via a Radical-Based Smiles Rearrangement Reaction,"The 1,9-ethanoiminomethano-bridged tetrahydrodibenzo[b,d]-furan 2, a non-natural isomer of the alkaloid (-)-galanthamine (1) varying in the manner in which the D-ring is annulated to the ABC-core, has been prepared in racemic form. The synthetic sequence starts with the cyclopropane 3 and involves intramolecular Heck alkenylation and radical-based Smiles rearrangement reactions as key steps. Unlike natural product 1, but as predicted by docking studies, compound 2 is not a potent inhibitor of acetylcholine esterase.",10.1021/jo501255c,2014-06-30,0.5881798714983961
Journal of the American Chemical Society,Total Synthesis of the Vancomycin Aglycon,"Full details of a diastereoselective total synthesis of the vancomycin aglycon are described. Two key aromatic nucleophilic substitution macrocyclizations with formation of the 16-membered diaryl ethers were enlisted for sequential CD and DE ring formations, an effective macrolactamization was developed for closure of the 12-membered biaryl AB ring system, and the defined order of CD, AB, and DE ring closures permitted selective thermal atropisomerism of the newly formed ring systems or their immediate precursors. This indirect control of the atropisomer stereochemistry allowed all synthetic material to be funneled into the one of eight atropdiastereomers characterizing the natural product.",10.1021/ja992577q,1999-10-15,0.5881776362847366
Angewandte Chemie International Edition,Synthesis of (−)‐Okilactomycin by a Prins‐Type Fragment‐Assembly Strategy,All things converge: A highly convergent synthesis of (−)-okilactomycin utilizes a Prins-type Maitland–Japp cyclization for the fragment assembly of two complex intermediates (see scheme). The synthesis also employs a highly diastereoselective Lewis acid promoted Diels–Alder reaction and an olefin ring-closing metathesis to close a strained 11-membered macrocycle.,10.1002/anie.201102037,2011-05-10,0.5881731717760268
European Journal of Organic Chemistry,Accessing Quinoxalines by Ring‐Opening/Cyclization/Detosylation/Aromatization of Activated Aziridines with 2‐Bromoanilines: Synthesis of Tyrphostin AG 1296,"Substituted 2‐arylquinoxalines have been synthesized by an unprecedented Cu I ‐catalyzed ring‐opening/cyclization reaction followed by detosylation/aromatization of activated aziridines with 2‐bromoanilines. The transformation efficiently accommodates a wide range of aziridines and 2‐bromoanilines to afford the desired quinoxaline frameworks in excellent yields (up to 86 %) as single regioisomers. The methodology has also been conveniently applied to the synthesis of tyrphostin AG 1296, a PDGF‐receptor tyrosine kinase inhibitor.",10.1002/ejoc.201700506,2017-05-18,0.5881718062539014
Journal of the American Chemical Society,Efficient and Divergent Total Synthesis of (−)-Epicoccin G and (−)-Rostratin A Enabled by Double C(sp<sup>3</sup>)–H Activation,"Dithiodiketopiperazines are complex polycyclic natural products possessing a variety of interesting biological activities. Despite their interest, relatively few total syntheses have been completed. We herein report the enantioselective, scalable, and divergent total synthesis of two symmetrical pentacyclic dithiodiketopiperazines, (−)-epicoccin G and (−)-rostratin A. A common intermediate was synthesized on a multigram scale from inexpensive, commercially available starting materials using an enantioselective organocatalytic epoxidation and a double C(sp 3 )–H activation as key steps, with the latter allowing the efficient simultaneous construction of the two five-membered rings. In addition to the cis,cis -fused target (−)-epiccocin G, the more challenging (−)-rostratin A, possessing two trans ring junctions, was obtained for the first time on a 500 mg scale through the optimization of each step and validation on multigram quantities. Both natural products were synthesized with high overall yields (13–20%). This study should facilitate access to this fascinating and yet understudied family of biologically active natural products.",10.1021/jacs.9b09359,2019-09-26,0.5881596708793795
Synthesis,A Facile Chiral Synthesis of the Lactone Moiety of Compactin and Mevinolin from (<i>R</i>)-<i>O</i>-Benzylglycidol,"All articles of this category A facile chiral synthesis of (4 R ,6 S )-4-hydroxy-6-hydroxymethyltetrahydro-2-pyrone ( 3 ) a key synthon for the lactone portion of compactin and mevinolin, is established using ( R )-O-benzylglycidol as starting material.",10.1055/s-1989-27310,1989-01-01,0.5881510702757876
Tetrahedron,Enantioselective synthesis of 2-isocephem and 2-oxa-isocephem antibiotics,,10.1016/s0040-4039(00)61006-7,1992-10-01,0.5881474838555809
Tetrahedron,An enantioselective formal synthesis of thienamycin,,10.1016/j.tetlet.2024.155132,2024-06-08,0.5881474838555809
Tetrahedron,Enantioselective synthesis of the top half of chlorothricolide,,10.1016/s0040-4039(00)61260-1,1992-08-01,0.5881474838555809
Tetrahedron,Enantioselective synthesis of (−)-indolizidine 167B,,10.1016/s0040-4039(99)00059-3,1999-02-01,0.5881474838555809
Tetrahedron,Enantioselective synthesis of the C5–C23 segment of biselyngbyaside,,10.1016/j.tetlet.2012.11.015,2012-11-10,0.5881474838555809
Tetrahedron,Enantioselective synthesis of α-aminopropargylphosphonates,,10.1016/j.tetlet.2007.04.124,2007-04-30,0.5881474838555809
Tetrahedron,Enantioselective synthesis of cyclohexene nitroaldehydes,,10.1016/s0040-4039(00)99195-0,1989-01-01,0.5881474838555809
Tetrahedron,An enantioselective synthesis of loracarbef (LY163892/KT3777),,10.1016/s0040-4039(01)80388-9,1989-01-01,0.5881474838555809
Tetrahedron,An enantioselective synthesis of (+)-pseudohygroline,,10.1016/s0040-4039(98)00253-6,1998-04-01,0.5881474838555809
Tetrahedron,Enantioselective synthesis of decarestrictine J,,10.1016/j.tetlet.2009.10.035,2009-10-14,0.5881474838555809
Tetrahedron,An enantioselective synthesis of (6R)-lactacystin,,10.1016/s0040-4039(00)61573-3,1993-10-01,0.5881474838555809
Tetrahedron,An enantioselective synthesis of (−)-slaframine,,10.1016/0040-4039(91)80195-c,1991-11-01,0.5881474838555809
Tetrahedron,Enantioselective synthesis of (+)-pinidine,,10.1016/s0040-4039(00)93419-1,1991-09-01,0.5881474838555809
Tetrahedron,Enantioselective synthesis of the hexahydrobenzofuran subunit of the avemectins and the milbenycins,,10.1016/s0040-4039(00)94443-5,1990-01-01,0.5881474838555809
Tetrahedron,An expeditious enantioselective synthesis of γ-lactones,,10.1016/s0040-4039(00)88894-2,1990-01-01,0.5881474838555809
Tetrahedron,Enantioselective synthesis of diarylcyclopropanecarboaldehydes by organocatalysis,,10.1016/j.tetlet.2016.10.097,2016-10-27,0.5881474838555809
Tetrahedron,Enantioselective deprotonation of the 8-oxabicyclo[3.2.1]octan-3-one: Synthesis of 8-oxa-norcocaines and 8-oxa-pseudonorcocaines,,10.1016/s0040-4039(99)00763-7,1999-06-01,0.5881474838555809
Tetrahedron,An enantioselective synthesis of phomopsolide D,,10.1016/j.tetlet.2004.07.011,2004-07-22,0.5881474838555809
Tetrahedron,Enantioselective formal synthesis of tridemethylisovelleral,,10.1016/j.tetlet.2006.11.122,2006-12-13,0.5881474838555809
Tetrahedron,Corrigendum to “Enantioselective synthesis of 1(R)-hydroxypolygodial”,,10.1016/j.tetlet.2006.01.076,2006-02-04,0.5881474838555809
Tetrahedron,An enantioselective synthesis of the C2–C16 segment of antitumor macrolide laulimalide,,10.1016/s0040-4039(00)00158-1,2000-04-01,0.5881474838555809
Tetrahedron,Enantioselective Synthesis of (S)-5-Aminopiperidin-2-one from (S)-Pyroglutaminol,,10.1016/00404-0399(50)17557-,1995-11-06,0.5881474838555809
Tetrahedron,Enantioselective synthesis of (R)-(−)-Cryptopleurine,,10.1016/0040-4039(94)02376-m,1995-02-01,0.5881474838555809
Tetrahedron,"Regio and enantioselective synthesis of 4-carbomethoxymethyl-1,4 dihydropyridines",,10.1016/s0040-4039(00)73518-0,1994-07-01,0.5881474838555809
Tetrahedron,Enantioselective synthesis of girolline,,10.1016/s0040-4039(00)93492-0,1991-09-01,0.5881474838555809
Tetrahedron,Enantioselective synthesis of indoloquinolizidines,,10.1016/0040-4039(91)80605-6,1991-08-01,0.5881474838555809
Tetrahedron,Enantioselective synthesis of 1(R)-hydroxypolygodial,,10.1016/j.tetlet.2005.04.020,2005-04-21,0.5881474838555809
Tetrahedron,"Enantioselective synthesis of all 2,4-dideoxyhexose stereoisomers",,10.1016/0040-4039(91)80592-t,1991-08-01,0.5881474838555809
Tetrahedron,Enantioselective synthesis of the top half of tetronolide,,10.1016/s0040-4039(00)60939-5,1992-10-01,0.5881474838555809
Tetrahedron,Enantioselective synthesis of (−)-barrenazines A and B,,10.1016/j.tetlet.2007.09.145,2007-10-01,0.5881474838555809
Tetrahedron,Enantioselective synthesis of (R)-deoxydysibetaine and (−)-4-epi-dysibetaine,,10.1016/j.tetlet.2007.05.007,2007-05-09,0.5881474838555809
Tetrahedron,Enantioselective synthesis of the aminoimidazole segment of dragmacidin D,,10.1016/s0040-4039(01)02331-0,2002-02-01,0.5881474838555809
Tetrahedron,"Enantioselective synthesis of (+)-(2S,3s)-3-ethynyltyrosine",,10.1016/s0040-4039(00)97811-0,1990-01-01,0.5881474838555809
Tetrahedron,"An enantioselective synthesis of (2S,3S)- and (2R,3S)-3-hydroxyleucine",,10.1016/s0040-4039(00)61763-x,1992-11-01,0.5881474838555809
Tetrahedron,"Enantioselective synthesis of (2R,3R)- and (2S,3S)-β-hydroxyornithine",,10.1016/j.tetlet.2006.04.055,2006-05-12,0.5881474838555809
Tetrahedron,Enantioselective synthesis of (+)-aspercyclide A,,10.1016/j.tetlet.2013.07.038,2013-07-15,0.5881474838555809
Tetrahedron,The first enantioselective synthesis of α-aminophosphinates,,10.1016/s0040-4039(03)00946-8,2003-05-19,0.5881474838555809
Tetrahedron,Enantioselective synthesis of (+)- and (−)-dihydrokawain,,10.1016/0040-4039(96)01429-3,1996-09-01,0.5881474838555809
Tetrahedron,Enantioselective Synthesis of C2-Symmetric Diols,,10.1016/00404-0399(50)0889k-,1995-07-03,0.5881474838555809
Tetrahedron,Enantioselective synthesis and stereochemical revision of communiols A–C,,10.1016/j.tetlet.2005.07.041,2005-07-28,0.5881474838555809
Tetrahedron,Enantioselective synthesis of (+)-magydardienediol,,10.1016/0040-4039(91)80536-f,1991-12-01,0.5881474838555809
Tetrahedron,Enantioselective synthesis of chromenes,,10.1016/s0040-4039(02)02614-x,2003-01-01,0.5881474838555809
Tetrahedron,Enantioselective synthesis of d- and l-α-methylcysteine with hydantoinase,,10.1016/j.tetlet.2007.03.040,2007-03-13,0.5881474838555809
Tetrahedron,Enantioselective synthesis of the bottom-half of chlorothricolide,,10.1016/s0040-4039(00)98725-2,1985-01-01,0.5881474838555809
Tetrahedron,Enantioselective synthesis of D-erythro-sphingosine,,10.1016/s0040-4039(00)94120-0,1983-01-01,0.5881474838555809
Tetrahedron,Enantioselective synthesis and absolute configurations of aculeatins A and B,,10.1016/j.tetlet.2005.09.146,2005-10-11,0.5881474838555809
Tetrahedron,"Enantioselective synthesis of α,β-unsaturated γ- and δ-lactams",,10.1016/s0040-4039(01)00561-5,2001-06-01,0.5881474838555809
Tetrahedron,Enantioselective synthesis of aminobenzazepinones,,10.1016/j.tetlet.2007.02.078,2007-02-21,0.5881474838555809
Tetrahedron,An enantioselective synthesis of (−)-alloyohimbane,,10.1016/s0040-4039(00)80533-x,1988-01-01,0.5881474838555809
Tetrahedron,An enantioselective synthesis of the C1C9 segment of antitumor macrolide peloruside A,,10.1016/s0040-4039(03)00744-5,2003-05-01,0.5881474838555809
Tetrahedron,Enantioselective synthesis of (+)-fortamine,,10.1016/s0040-4039(00)73653-7,1993-05-01,0.5881474838555809
Tetrahedron,Enantioselective synthesis of 2-benzothiazolyl oxiranes,,10.1016/s0040-4039(97)01298-7,1997-08-01,0.5881474838555809
Tetrahedron,Enantioselective synthesis of C2-symmetric diols,,10.1016/0040-4039(95)00889-k,1995-07-01,0.5881474838555809
Tetrahedron,"An enantioselective synthesis of (1S,2S)-pseudoephedrine",,10.1016/s0040-4039(99)02106-1,2000-02-01,0.5881474838555809
Tetrahedron,Enantioselective synthesis of goniobutenolides A and B,,10.1016/0040-4039(95)00166-a,1995-03-01,0.5881474838555809
Tetrahedron,Enantioselective synthesis of (S)-5-aminopiperidin-2-one from (S)-pyroglutaminol,,10.1016/0040-4039(95)01755-7,1995-11-01,0.5881474838555809
Tetrahedron,An enantioselective synthesis of a 4-fluoromethyl-azetidinone,,10.1016/s0040-4039(01)90010-3,1984-01-01,0.5881474838555809
Tetrahedron,Enantioselective synthesis of α-hydroxylated enterolactone and analogs,,10.1016/s0040-4039(01)00907-8,2001-07-01,0.5881474838555809
Tetrahedron,"The enantioselective synthesis of poison-frog alkaloids (−)-203A, (−)-209B, (−)-231C, (−)-233D, and (−)-235B″",,10.1016/j.tetlet.2005.11.047,2005-11-29,0.5881474838555809
Organic Letters,"Iron-Catalyzed 1,5-Enyne Cycloisomerization via 5-<i>Endo-Dig</i> Cyclization for the Synthesis of 3-(Inden-1-yl)indole Derivatives","-catalyzed 1,5-enyne cycloisomerization via 5-endo-dig cyclization is described for the synthesis of 3-(1-indenyl)indole derivatives. Since a variety of 1,5-enynes are readily accessible via Heck-Suzuki coupling, this strategy provides a rapid and easy access to a wide range of highly substituted 3-(1-indenyl)indoles in good yields.",10.1021/acs.orglett.6b03544,2016-12-07,0.5881468212257883
Journal of Organic Chemistry,Palladium-Catalyzed Potassium Enoxyborate Alkylation of Enantiopure Hajos−Parrish Indenone To Construct Rearranged Steroid Ring Systems,Here we report the stereo- and regiospecific C-6 alkylation of a trans-inden-5-one (from optically pure Hajos-Parrish ketone) with allylic electrophiles. Use of this alkylation procedure has led to an improved synthesis of the benz[f]indene ring system and the first enantiospecific total syntheses of the cyclopenta[b]anthracene and cyclopenta[b]phenanthrene ring systems (two synthetic routes).,10.1021/jo070530e,2007-05-27,0.5881461506572637
European Journal of Organic Chemistry,"New Diastereoselective Route to 2‐Substituted <i>cis</i>‐(2<i>S</i>,5<i>S</i>)‐ and <i>trans</i>‐(2<i>S</i>,5<i>R</i>)‐5‐Alkylpyrrolidines as Indolizidine and Pyrrolizidine Scaffolds","Abstract A new and short stereoselective route to the synthesis of enantiopure cis ‐2,5‐disubstituted pyrrolidines as indolizidine or pyrrolizidine scaffolds has been developed. The method, which uses ( S )‐pyroglutamic acid as a chiral starting material, is based on the ring opening of N ‐protected γ‐lactams by alkyl phenyl sulfone carbanions, followed by desulfonylation and reductive amination of alkyl γ‐amino ketones. The diastereoselectivity depends on the substitution of the starting γ‐lactams, and on the alkyl group of the phenyl sulfone. Total cis diastereoselectivity was observed in the formation of tert ‐butyl 5‐alkylprolinates. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2003)",10.1002/ejoc.200300393,2003-10-16,0.588141945323843
Journal of Organic Chemistry,"Thermal Ring Contraction of Dibenz[<i>b,f</i>]azepin-5-yl Radicals: New Routes to Pyrrolo[3,2,1-<i>jk</i>]carbazoles","Flash vacuum pyrolysis (FVP) of N-allyl- or N-benzyldibenz[b,f]azepine at temperatures from 750 to 950 degrees C gives pyrrolo[3,2,1-jk]carbazole as the major product. The mechanism of the ring contraction involves dibenzazepin-1-yl radical formation, followed by transannular attack and formation of a 2-(indol-1-yl)phenyl radical which cyclizes. The mechanism is supported by independent generation of 2-(indol-1-yl)phenyl radicals by two different methods, and the use of 1-(2-nitrophenyl)indole as a radical generator gives an optimized synthetic route to pyrrolo[3,2,1-jk]carbazole (54% overall yield in two steps from indole). The first substituted pyrrolo[3,2,1-jk]carbazoles have been synthesized by FVP methods and also by reactions of the parent compound with electrophiles, leading to a range of 4-substituted pyrrolocarbazoles.",10.1021/jo800637u,2008-08-12,0.5881373313673108
Tetrahedron,Stereoselective synthesis of 1α-hydroxyvitamin D3 A-ring synthons by palladium-catalyzed cyclization,,10.1016/s0040-4039(00)93501-9,1991-09-01,0.5881283388514432
Tetrahedron,A new synthetic method of 3-acyltetronic acid derivatives and its application to the synthesis of isoaspertetronin a (isogregatin A),,10.1016/s0040-4039(00)88588-3,1982-01-01,0.5881283275065162
Tetrahedron,Improved large-scale synthesis of phenylisoserine and the taxol C-13 side chain,,10.1016/s0040-4039(02)02434-6,2003-01-01,0.5881261159346853
Tetrahedron,A stereocontrolled route to optically active 1-methyl carbapenems,,10.1016/s0040-4039(00)83988-x,1986-01-01,0.5881259640997367
Synlett,Radical Cyclizations as Key Step for the Stereoselective Synthesis of Bi- and Tricyclic Sesquiterpene Lactones,"A strategy towards the stereoselective synthesis of bi- and tricyclic sesquiterpene lactones is reported. As key step radical cyclizations of appropriately functionalized trans-4,5-disubstituted γ-butyrolactones, which are readily available from methyl 2-furoate, were carried out to give rise to 5,6-, 5,7- and 5,7,5-ring systems in diastereo- and enantiomerically pure form.",10.1055/s-2005-864827,2005-03-23,0.5881243676586235
Journal of Organic Chemistry,"Total Synthesis of a Potent Proinflammatory 5-Oxo-ETE and Its 6,7-Dihydro Biotransformation Product","The first total synthesis of a potent inflammatory mediator 5-oxo-6( E ),8( Z ),11( Z ),14( Z )-eicosatetraenoic acid (5-oxo-ETE) 2 and its biotransformation product 6,7-dihydro-5-oxo-ETE 5 is reported. A convergent synthesis for the unstable title compounds is accomplished via two synthons, dithiolane aldehyde 13 and bisdienyl phosphonium bromide 19 . The synthetic 5-oxo-ETE 2 and its 8,9-trans isomer 3 were used to unequivocally confirm the structure of the biologically derived mediators. In addition, using synthetic 6,7-dihydro-5-oxo-ETE 5 we have been able to identify in neutrophils the formation of 6,7-dihydro-5-oxo-ETE 5 .",10.1021/jo9716993,1998-01-01,0.588123617363718
Synthesis,"First Synthesis of a Conformationally Restricted 2,2’-Bipyrrole","A seven-step procedure was developed for the preparation of the cyclooctadiene-annulated 2,2’-bipyrrole 14, starting from commercially available benzyl bromoacetate 6 and adiponitrile 7. Although all transformations carried out had to be sufficiently selective to produce the desired functionalities on both sites of the respective dipyrroles, acceptable to good yields were observed throughout the synthesis. The paper reports synthetic and spectroscopic details of the new compounds.",10.1055/s-2002-19305,2002-07-26,0.588104008930473
Tetrahedron,Efficient synthesis and anion recognition of a colorimetric preorganized tripodal thiourea compound,,10.1016/j.tetlet.2012.02.069,2012-02-20,0.5881005240163846
Tetrahedron,"A novel strategy for the chiral 2,4,5-triol moiety and its application to the synthesis of seimatopolide A and (2S,3R,5S)-(−)-2,3-dihydroxytetradecan-5-olide",,10.1016/j.tetlet.2012.08.027,2012-08-14,0.5880985939429323
Tetrahedron,"Synthesis of permethylated α-d-mannosylacetic acid, a new type of bioconjugate",,10.1016/s0040-4039(02)02770-3,2003-02-01,0.5880921543069747
Tetrahedron,"Synthesis of Symmetrical and Unsymmetrical 1,2-Diketones through Cathodic Intramolecular Coupling of Diesters.",,10.1016/s0040-4039(97)01573-6,1997-09-01,0.5880869414121886
Tetrahedron,"Synthesis of 2,3-dimethyl,-1,4-diazacycl[3.2.2]Azine. a novel heteroaromatic system",,10.1016/s0040-4039(01)82839-2,1966-01-01,0.5880813562992714
Synthesis,"A Novel Synthesis of 2,2-Dimethyl-5-hydroxychroman",,10.1055/s-1975-23768,1975-01-01,0.5880813562992714
Tetrahedron,"Thermal rearrangements of C-(4-Oxo-4H[1]benzopyran-3-yl)-N-phenylnitrone-a route to novel quinolino[2,3-b]chroman-12-ones",,10.1016/s0040-4039(98)01362-8,1998-09-01,0.5880785012620164
Organic Process Research & Development,"Optimization of Manganese Coupling Reaction for Kilogram-Scale Preparation of Two Aryl-1,3-dione Building Blocks","Aryl-1,3-diones represent a promising new class of herbicidal acetyl-CoA carboxylase (ACCase) inhibitors. The original synthesis of this structural motif employed in the research phase involved a selenium oxide mediated oxidation, the use of diazoacetate and aryl lead reagents, and a low temperature oxidation of an aryl lithium intermediate, so it was not well suited to large scale synthesis. For kilogram scale synthesis of the two aryl-1,3-dione building blocks ( 3 and 4 ), we developed an alternative route which employs a manganese or manganese–copper catalyzed alkyl Grignard coupling and a semi-pinacol rearrangement of an epoxide as the key steps. The optimized conditions could be of general interest as scalable methods for the synthesis of 2-alkyl substituted benzaldehydes and of 2-aryl-1,3-diones.",10.1021/acs.oprd.7b00241,2017-08-21,0.5880775288297565
Tetrahedron,"Bifunctional chiral synthons via biochemical methods. 5. Preparation of (S)-ethyl hydrogen-3-hydroxyglutarate, key intermediate to (R)-4-amino-3-hydroxybutyric acid and L-carnitine.",,10.1016/s0040-4039(01)81572-0,1984-01-01,0.5880699649124354
Organic Letters,Enantioselective Synthesis of ABCF Tetracyclic Framework of <i>Daphniphyllum</i> Alkaloid Calyciphylline N,"Efforts toward the enantioselective synthesis of Daphniphyllum alkaloid calyciphylline N which leads to efficient preparation of the ABCF tetracyclic framework containing three bridgehead all-carbon quaternary stereocenters are described. This synthetic work features the utilization of an asymmetric conjugate addition to install the C5 all-carbon quaternary center, an efficient successive inter/intramolecular aldol sequence to build the critical bicyclo[2.2.2]octanone BC core, and a ring closing metathesis reaction followed by stereoselective Nagata conjugate cyanation to deliver the functionalized F ring.",10.1021/acs.orglett.8b02202,2018-08-09,0.5880685501069226
Organic Letters,Scalable Synthesis of Mycocyclosin,"We report herein the scalable total synthesis of the secondary metabolite, mycocyclosin, initially isolated from Mycobacterium tuberculosis. Mycocylosin bears a highly strained 3,3'-dityrosine biaryl system which arises biosynthetically from an intramolecular oxidative dehydrogenative cross-coupling of cyclo(l-Tyr-l-Tyr) (cYY) catalyzed by the P450 enzyme CYP121. CYP121 is found exclusively in M. tuberculosis. Scalable access to mycocyclosin and related derivatives via a Pd(II)-catalyzed macrocyclization is anticipated to facilitate the biological evaluation of these compounds as novel tuberculosis antimicrobials.",10.1021/acs.orglett.8b00894,2018-04-27,0.5880551654573598
Tetrahedron,"Synthesis of unsymmetrically substituted pyrene derivatives through (6-bromo-3,8-dibutylpyren-1-yl)trimethylsilane",,10.1016/j.tetlet.2011.09.089,2011-09-23,0.5880482722747455
Synlett,The Total Synthesis of Pygmaeocin C,"Making use of a recently developed intramolecular Friedel-Crafts alkylation process as the key operation, the first total synthesis, in racemic form, of pygmaeocin C has been achieved.",10.1055/s-2004-837222,2005-01-01,0.5880429626945755
Journal of Organic Chemistry,Asymmetric Total Syntheses of (+)-Cheimonophyllon E and (+)-Cheimonophyllal,"The highly enantiocontrolled total syntheses of natural (+)-cheimonophyllon E (5) and (+)-cheimonophyllal (6), biologically intriguing oxygenated bisabolane-type sesquiterpenoids, have been completed. The present synthetic strategy featured the use of an asymmetric aldol-type reaction for preparing in the first synthetic step an optically active 6-C-substituted 3-methyl-2-cyclohexenone derivative. Thus, a Mukaiyama aldol reaction of 1-methyl-3-silyloxy-1,3-cyclohexadiene 31 with alpha,beta-unsaturated aldehyde 11 in the presence of a chiral (acyloxy)borane (CAB)-type Yamamoto catalyst 33 proceeded with high levels of both diastereo- and enantioselectivities. The predominant aldol adduct, syn-9, was transformed into gamma,delta-epoxy allylic alcohol 8 by a nine-step sequence, including the substrate-controlled 1,2-reduction of enone, syn-12, also the epoxidation of allylic alcohol 15. Epoxy-alcohol 8 underwent 5-exo-cyclization in a high regioselective manner under acidic conditions to produce a bicyclic key intermediate (+)-7, which was eventually efficiently converted to (+)-cheimonophyllon E (5) or (+)-cheimonophyllal (6).",10.1021/jo0203140,2002-08-29,0.5880425815884358
Tetrahedron,Synthesis of key intermediates for a concise and convergent approach to the marine natural product eleutherobin,,10.1016/s0040-4039(99)01956-5,1999-12-01,0.5880391465313601
Synthesis,Synthesis of All Stereoisomers and Some Congeners of Isocytoxazone,"cis-Isocytoxazone 2a and trans-isocytoxazone 2b, structural isomers of the antiasthmatic agent cytoxazone (-)-1, and their 5-substituted congeners 23-28 have been prepared. Aldol reaction of para-substituted benzaldehydes with 7-chloro-1-methyl-5-phenyl-1,4-benzodiazepin-2-one, followed by separation of diastereomeric racemates afforded 3-10. Acid-catalyzed 1,4-benzodiazepine ring opening, and transformation of the methyl esters of β-aryl-β-hydroxy-α-amino acids (11-16) via 4-methoxycarbonyl derivatives of 1,3-oxazolidin-2-one (17-22) and their reduction afforded the target oxazolidin-2-one derivatives 23-28. Racemic isocytoxazones 2a and 2b were prepared by an independent route starting from 4-methoxystyrene epoxide. Pure enantiomers of these diastereomeric racemates were separated by HPLC chromatography on chiral stationary phases. Their CD spectra, along with those of previously prepared enantiomers of cis-cytoxazone 1a and trans-cytoxazone 1b are discussed.",10.1055/s-2003-37353,2003-01-01,0.5880133829305804
Organic Letters,Iodo-cyclizations: Novel Strategy for the Total Syntheses of Polyrhacitide A and <i>epi</i>-Cryptocaryolone,"Highly stereoselective total syntheses of polyrhacitide A and epi-cryptocaryolone have been achieved in 11 steps with high overall yield of 24% and 28%, respectively, following a recently developed strategy for the construction of trans-2,6-disubstituted-3,4-dihydropyrans. In this report, the versatility of iodo-cyclization for the total syntheses of polyrhacitide A and epi-cryptocaryolone is demonstrated.",10.1021/ol1029854,2011-01-07,0.5880112148053079
Tetrahedron,"Total synthesis of (+)-pedamide. A new, remote controlled asymmetric induction",,10.1016/s0040-4039(00)88690-6,1982-01-01,0.5880102727805517
Journal of the American Chemical Society,Intramolecular Rhodium-Catalyzed [(3+2+2)] Carbocyclization Reactions with Dienylidenecyclopropanes: A Concise and Stereoselective Total Synthesis of the Sesquiterpene (+)-Zizaene,"The development of an intramolecular rhodium-catalyzed [(3+2+2)] carbocyclization reaction of alkylidenecyclopropanes (ACPs) tethered to 1,4- and 1,5-skipped dienes is described. This transformation offers a new approach for the construction of bridged tricyclic compounds with up to three quaternary centers, which are suitable for the synthesis of challenging bioactive natural products. For instance, the synthetic utility of this transformation is illustrated through a concise asymmetric total synthesis of the sesquiterpene (+)-zizaene in ten steps from a commercially available starting material.",10.1021/jacs.2c10923,2023-02-06,0.588008748578541
Tetrahedron,Novel activating and capping reagents for improved hydrogen-phosphonate DNA synthesis,,10.1016/s0040-4039(00)82467-3,1988-01-01,0.5880016008198797
European Journal of Organic Chemistry,Tandem Reductive Cyclization–Dehydration Approach for the Synthesis of Cryptolepine Hydroiodide and Its Analogues,"Abstract A new and convenient synthesis of the indoloquinoline alkaloid cryptolepine hydroiodide is described through a tandem reductive cyclization–dehydration approach. This methodology employs a C–C bond formation through the C‐2 lithiation of a benzenesulfonyl‐protected indole and a C–N bond formation through a nitrene intermediate, which is produced from different organophosphorus reagents, to give a fused tetracyclic compound. The versatility of this method is demonstrated by the syntheses of a series of cryptolepine salts with substituents on the indole as well as the quinoline ring.",10.1002/ejoc.201201586,2013-02-21,0.5880000077074464
Synthesis,"Simple and Efficient Access to 3-Ethoxycarbonylpyrroles, Benzofurans, and Naphthofurans","An efficient method was developed for the synthesis of pyrrole and furan derivatives from enamines, phenols, and naphthols. The key steps involve iodocyclization and alumina-induced dehydroiodination reactions.",10.1055/s-0029-1217053,2009-10-19,0.5879896326448397
Synlett,Stereoselective Synthesis of 3-(5-Benzoyl-1-methyl-1H-pyrrol-2-yl)-2-azetidinone Derivatives via an in Situ Generated Ketene,"A short route toward β-lactams from tolmetin has been developed. In the key step, a ketene was generated on the C-2 of pyrrole ring and reacted with aromatic imines to form trans-β-lactams as the only observed products. The identification of the ketene was confirmed by reaction with the stable free radical TEMPO (TO·).",10.1055/s-0036-1558974,2017-04-06,0.5879870234849386
Tetrahedron,An improved method of oxazolidinone hydrolysis in the asymmetric synthesis of α-alkylprolines,,10.1016/s0040-4039(00)73294-1,1994-07-01,0.5879861266756983
Synthesis,"A New Synthesis of cis-Cyclobut-3-ene-1,2-dicarboxylic Anhydride","All articles of this category The title compound was prepared in two steps by [2 + 2] photochemical cycloaddition between ( E )-1,2-dichloroethene and maleic anhydride followed by reductive chlorine elimination with activated zinc. This safe synthetic route gave cis -cyclobut-3-ene-1,2-dicarboxylic anhydride in good overall yield and could be carried out on a multigram scale. cyclobutenes - photochemistry - [2 + 2] cycloaddition - reduction - activated zinc",10.1055/s-1999-3441,1999-04-01,0.5879802038054026
Tetrahedron,Synthesis of 3-chloro- and 3-bromobenzocyclopropene,,10.1016/s0040-4039(01)92696-6,1977-01-01,0.5879765927372738
Tetrahedron,"Synthesis of 2-chloro-1,3-benzodioxole",,10.1016/s0040-4039(01)88869-9,1969-01-01,0.5879765927372738
Tetrahedron,Development of tetrahydrofuran chiral synthons by enzymatic approach: Improved synthesis of a strong agonist of platelet activating factor,,10.1016/s0040-4039(00)91866-5,1992-02-01,0.5879759222141672
Organic Process Research & Development,Process Development and Scale-Up of a PPARγ Agonist: Selection of the Manufacture Route,"Two short, high-yielding routes to the selective PPARγ agonist GSK376501A were developed and carried out on scale. The key bond -forming reaction in each synthesis was the substitution of a 3,5-difluoro or 3,5-dibromo aryl intermediate with 2-methoxyethanol. A nucleophilic aromatic (S N Ar) substitution reaction under basic conditions was developed for the aryl fluoride substrate. The 3,5-dibromo aryl halide intermediate required copper-catalyzed conditions to achieve substitution of the second bromide. In addition, a 2-methoxyethanol decomposition pathway to generate methanol and ethylene oxide under basic reaction conditions as well as its effect on impurity formation, was elucidated. Both the difluoro and dibromo intermediates were considered as the basis for the final route of manufacture. The difluoro substrates were chosen due to straightforward chemistry, controllable impurity profile, and ease of fluoride removal.",10.1021/op800211c,2008-12-05,0.5879616479481096
Tetrahedron,Synthesis of new [2]rotaxane including a macrocyclic receptor and a photochromic unit,,10.1016/j.tetlet.2008.03.110,2008-03-29,0.5879439165073079
Journal of Organic Chemistry,Cuprate-Mediated Synthesis and Biological Evaluation of Cyclopropyl- and <i>tert-</i>Butylfarnesyl Diphosphate Analogs,"The novel farnesyl diphosphate (FPP) analog 3-cyclopropyl-3-desmethylfarnesyl diphosphate (3-cpFPP, 1) was designed as a potential mechanism-based inhibitor of the FPP-utilizing enzyme protein-farnesyl transferase (PFTase). The key step in the synthesis of 1 involved the stereoselective coupling of vinyl triflate 8 with a lower order cyclopropyl cyanocuprate to afford the desired cyclopropyl ester 13. The sterically encumbered analog 3-desmethyl-3-tert-butylfarnesyl diphosphate (3-tbFPP, 7) was synthesized via a similar route. The use of the more reactive higher order tert-butyl cyanocuprate led to lower yields of ester 11, the key intermediate in the synthesis of 7. Biological evaluation of 3-cpFPP demonstrates that it is not a time-dependent inhibitor of recombinant yeast PFTase. Instead, 3-cpFPP is an alternative substrate for this enzyme that exhibits a K(m) comparable to FPP and a k(cat) only 5-fold lower than the natural substrate. In contrast, 3-tbFPP is an exceptionally poor substrate for yeast PFTase and acts as an inhibitor of this enzyme.",10.1021/jo9614203,1996-11-15,0.5879432987289204
Organic Letters,New Synthetic Method for Indole-2-carboxylate and Its Application to the Total Synthesis of Duocarmycin SA,"The sequential coupling and cyclization reactions between aryl halides and methyl propiolate were investigated. The electron-withdrawing groups on the aromatic ring are essential for producing the methyl indole-2-carboxylate derivatives. On the other hand, the presence of an extra methyl propiolate and Pd(PPh3)4 were required to provide an efficient catalytic system for the cyclization reactions. This reaction was used for the total synthesis of duocarmycin SA.",10.1021/ol0489548,2004-07-23,0.5879353123651223
Tetrahedron,A synthesis of 7-methoxycephalosporin and its novel rearrangement,,10.1016/s0040-4039(01)83121-x,1977-01-01,0.5879348990424612
Synlett,Synthesis of the ABC Ring System of Paclitaxel: Formation of the 8-Membered B Ring by Intramolecular Alkylation,All articles of this category (opens in new window),10.1055/s-2002-19359,2002-01-01,0.5879290668828395
Organic Letters,Synthesis of Four Illudalane Sesquiterpenes Utilizing a One-Pot Diels–Alder/Oxidative Aromatization Sequence,"The concise, divergent total syntheses of four illudalane sesquiterpenes using an indanone as the key intermediate are reported. The key elements in these total syntheses, which involve only four to six operational steps, consist of a Suzuki cross-coupling and a one-pot Diels-Alder/oxidative aromatization reaction.",10.1021/acs.orglett.9b02511,2019-08-23,0.5879156921157443
Synthesis,"A Concise, Novel Route to 1,3-Benzoxathian Derivatives","Novel 1,3-benzoxathian derivatives were successfully prepared in a one-pot process via a tandem ring-closure/β-elimination pathway from easily accessible o-thio-substituted phenols.",10.1055/s-0029-1217016,2009-09-23,0.5879145879491591
Synlett,"An Improved Synthesis of Optically Pure 4-Boc-5,6-Diphenylmorpholin-2-one and 4-Cbz-5,6-Diphenylmorpholin-2-one","A convenient synthesis of optically pure 4-Boc-5,6-diphenylmorpholin-2-one and 4-Cbz-5,6-diphenylmorpholin-2-one by reaction of (+)- or (-)-2-amino-1,2-diphenylethanol with ethyl bromoacetate, followed by N-protection, and p-TsOH-mediated ring-closure is described. The title compounds can be used as synthons for the asymmetric synthesis of N-protected α-amino acids. These lactones are quite stable to storage and handling.",10.1055/s-2005-863740,2005-01-01,0.5879103082506558
Synlett,Enantioselective Taxanes Approach Using Both Enantiomers of the Same Building-Block. Part 1: Taxol<sup>®</sup>A-Ring Subunit,"An efficient enantioselective synthesis of fully-oxygenated Taxol® A-ring subunit has been achieved using (-)-karahana lactone, (-)-2, as an enantiopure starting building-block and a diastereoselective allylic hydroxylation as the key step.",10.1055/s-2002-32968,2002-01-01,0.5879086068732023
Tetrahedron,Practical chemoenzymatic synthesis of a 3-pyridylethanolamino β3 adrenergic receptor agonist,,10.1016/s0040-4039(99)01353-2,1999-09-01,0.5879061646038939
Synthesis,"1,2-Epimino-3,4-epoxybutane: A Versatile Chiral Building Block","All articles of this category The synthesis of enantiomerically pure 1,2-epimino-3,4-epoxy-( N -toluenesulfonyl)butane ( 6 ) in the S,R- ( erythro ) and R,R -( threo ) configurations is described. This building block offers a new route to targets with an 1,2-aminohydroxy functionality. As an example, the new 1,4-biselectrophile is employed in a cyclopentane synthesis. amino alcohols - domino reactions - epoxides - ring opening - cyclopentanes",10.1055/s-2001-12359,2001-01-01,0.5879058536222354
Journal of Organic Chemistry,Total Synthesis of Epothilone D: The Nerol/Macroaldolization Approach,"A highly convergent and stereocontrolled synthesis of epothilone D (4) is reported. Key features are a cheap and Z-selective synthesis of the northern half based on nerol and acetoacetate and chromium(II)-mediated Reformatsky reactions as a powerful tool for chemoselective asymmetric carbon-carbon bond formations, including an unusual stereospecific macroaldolization.",10.1021/jo401355r,2013-09-30,0.5879057896073391
Angewandte Chemie International Edition,"Total Synthesis of Mutanobactins A, B from the Human Microbiome: Macrocyclization and Thiazepanone Assembly in a Single Step","We report the first total syntheses of tricyclic mutanobactins A and B, lipopeptides incorporating a thiazepanone, isolated from Streptococcus mutans, a member of the human oral microbiome. A rapid, solid-phase peptide synthesis (SPPS) based route delivers these natural products from a cascade of cyclization reactions. This versatile process was also employed in a streamlined synthesis of mutanobactin D. Additionally, we provide an independent synthesis of a truncated mutanobactin A analog, utilizing a novel thiazepanone amino acid building block.",10.1002/anie.202203051,2022-05-20,0.5879045510563983
European Journal of Organic Chemistry,Synthesis of a New Class of <i>C</i><sub>2</sub>‐Symmetrical Biheteroaryls by Ammonium Cerium(IV) Nitrate Mediated Dimerization of 2‐(Furan‐3‐yl)pyrroles,"Abstract Polyfunctionalized 2‐(furan‐2‐yl)pyrroles and 2‐(furan‐3‐yl)pyrroles derived from 2‐azetidinone‐tethered allenes by two independent cerium(IV)‐mediated single‐electron oxidations provided a (4‐oxopent‐2‐enoyl)pyrrole and 3,3′‐bis(pyrrol‐2‐yl)‐2,2′‐bifurans, respectively. Access to the oxidation precursors was achieved by regiocontrolled cyclization of β‐allenamine intermediates derived from selective β‐lactam nucleus breakage of 2‐azetidinone‐tethered allenols.",10.1002/ejoc.200901314,2009-12-22,0.5879030443179959
Organic Letters,A Short Synthetic Pathway to a Fully-Functionalized Southern Hemisphere of the Antitumor Macrolide Bryostatin 1,"[reaction--see text] An 18-step asymmetric synthesis of the bryostatin 1 ""southern hemisphere"" fragment (1) has been developed. Key steps include an aldol reaction between 6 and 7 and a dehydration to establish the (E)-exocyclic alkene in 2 and a stereoselective Luche reduction and protection with TESOTf to access 1.",10.1021/ol016800b,2001-10-13,0.5879011362976798
Journal of Organic Chemistry,Asymmetric Synthesis of .beta.-Lactams. Highly Diastereoselective Alkylation of Chiral 2-Cyano Esters,Enolates derived from 10-(dicyclohexylsulfamoyl)isobornyl 2-substituted-2-cyanoacetates were alkylated with very good yield and high diastereoselectivity. The reduction of the resulting reaction products and subsequent cyclization of the β-amino acids led to the corresponding β-lactam in high yields. This result paves the way for the development of a versatile and efficient asymmetric synthesis of enantiomerically pure (R)- and (S)-C(3)-disubstituted β-lactams.,10.1021/jo00088a034,1994-05-01,0.5878981058531373
European Journal of Organic Chemistry,"Iodine‐Catalyzed [3 + 3] Cycloaddition Strategy for the Synthesis of Carbon Substituted 1, 4‐ Piperazines","Piperazine moiety is found to be the most promising core in several biologically active compounds and some of the marketed blockbuster drugs such as Glivec (imatinib) and Viagra (sildenafil). However, the substitution pattern in the piperazine ring reveals that the synthesis of carbon substituted scaffold remains a challenge without prefunctionalized piperazine core. Herein, a straightforward, catalytic, one pot, metal‐free, benign synthetic route is disclosed to synthesize carbon substituted 1, 4‐piperazines from easily available starting materials. This synthetic pathway is free from cautious imine synthesis and previously reported well‐articulated starting material which are leading to limited substrate scope. The approach involves in situ generation of 1, 3 dipoles and their [3 + 3] cycloaddition catalyzed by iodine in water.",10.1002/ejoc.202500480,2025-06-26,0.5878924426731953
Synlett,"A Scaleable Synthesis of 3-Hydroxy-1,5-naphthyridine-4-carbaldehyde","A scaleable synthesis of 3-hydroxy-1,5-naphthyridine-4-carbaldehyde is described. 3-Amino-5-methoxy-4-methyl-pyridine underwent the Skraup reaction to give the corresponding 1,5-naphthyridine which, upon treatment with DMF-DMA in the presence of catalytic amount of LiOH, provided the N,N-dimethyl enamine intermediate. Oxidative cleavage, followed by removal of the methyl ether afforded the titled product.",10.1055/s-0029-1218577,2009-12-11,0.5878884919383758
Synlett,Synthesis of JKLM Ring Fragment of Ciguatoxin via Acetylene-Cobalt Strategy,"A stereoselective synthesis of the JKLM ring fragment has been achieved through a coupling between two segments via heteroconjugate addition, seven-membered ether ring formation mediated by an acetylene cobalt complex and spiroketalization reaction.",10.1055/s-2003-37533,2003-01-01,0.5878850678667942
Synlett,"A New Versatile Route to the Synthesis of a Novel Series of Highly Substituted 1,1′-Carbonylbispyrazole Derivatives","The reaction of 1 H -pyrazole-1-carbohydrazide with various α,β-unsaturated nitriles under suitable conditions leads to a cyclocondensation reaction, thereby providing a novel route for the synthesis of a series of highly substituted 1,1′-carbonylbispyrazole derivatives.",10.1055/s-0033-1340737,2014-02-14,0.5878843747547641
Journal of the American Chemical Society,Copper-Catalyzed Enantioselective Substitution of Allylic Carbonates with Diboron:  An Efficient Route to Optically Active α-Chiral Allylboronates,"A method for the synthesis of alpha-chiral allylboronates featuring the Cu(I)-catalyzed enantioselective substitution of readily available allylic carbonates with a diboron is described. Using this method, various alpha-chiral allylboronates, including functionalized allylboronates, were successfully synthesized, with high enantiomeric purity.",10.1021/ja076634o,2007-11-08,0.5878750415427192
Tetrahedron,"Asymmetric total synthesis of (+)-phomalactone, (+)-acetylphomalactone and (+)-asperlin utilizing a novel syn-selective C4-oxa-vinylogous urethane","The total synthesis of three natural products isolated from Nigrospora sp., Phoma sp., and Aspergillus nidulans1 starting from an aldol reaction with a homochiral C4-oxa-vinylogous urethane is described. Inherent stereoselectivity of the aldol reaction and overall alacrity of molecular construction are discussed.",10.1016/s0040-4039(98)02675-6,1999-02-01,0.5878724380146023
Organic Letters,Synthesis of Ring B Unsaturated Estriols. Confirming the Structure of a Diagnostic Analyte for Smith−Lemli−Opitz Syndrome,"[structure: see text] Brief partial syntheses are described for ring B unsaturated estriols, which are candidate metabolites diagnostic for Smith-Lemli-Opitz syndrome prenatally. These steroids are also likely metabolites of the Premarin preparation used in estrogen replacement therapy. Equilin (8) was converted in three steps to 7-dehydroestriol, which was isomerized to 8-dehydroestriol. The simplicity of the transformations belies the lability of these previously inaccessible metabolites and their synthetic precursors.",10.1021/ol016224j,2001-07-17,0.587871943070485
Journal of the American Chemical Society,A Catalytic Asymmetric Bioorganic Route to Enantioenriched Tetrahydro- and Dihydropyranones,"A conceptually novel approach to hetero Diels-Alder adducts of carbonyl compounds is described using as the key steps an antibody-mediated kinetic resolution of hydroxyenones followed by a ring-closure process. Various beta-hydroxyenones proved to be very good substrates for antibodies 84G3- and 93F3-catalyzed retro-aldol reactions, allowing the preparation of highly enantiomerically enriched (up to 99% ee) precursors of pyranones. An attractive feature of this methodology is the possibility to convert these acyclic-enantioenriched beta-hydroxyenones into tetrahydropyranones by a conventional Michael-type addition procedure or into the corresponding dihydropyranones using an alternative palladium-catalyzed oxidative ring closure. For the palladium-mediated cyclization, a biphasic system has been implemented that allows the direct preparation of enantiopure dihydropyranones from the corresponding racemic aldol precursors using a sequential antibody-resolution/palladium-cyclization strategy, without isolation of the intermediate enantioenriched hydroxyenones. This bioorganic route is best applied to the preparation of hetero Diels-Alder adducts otherwise derived from less nucleophilic dienes and unactivated dienophiles.",10.1021/ja043925d,2005-01-15,0.5878651694237714
Angewandte Chemie International Edition,Enantioselective Total Synthesis of the Nonisoprenoid Sesquiterpene (−)-Kumausallene,"An acyl radical cyclization to form the bicyclic core of (-)-kumausallene (1) was the key feature in the 14-step, enantioselective synthesis. This work demonstrates that the bromoallene unit is robust enough to withstand multiple synthetic operations and provides the unambiguous assignment of the absolute configuration of the bromoallene.",10.1002/(sici)1521-3773(19991102)38:21<3175::aid-anie3175>3.0.co;2-m,1999-11-02,0.5878640898185503
Synlett,Synthetic Studies toward Potent Cytotoxic Agent Amphidinolide B: Synthesis of the C<sub>8</sub>-C<sub>18</sub> Fragment,,10.1055/s-1999-2544,1999-01-01,0.587860970894356
Organic Letters,Structural Diversity Based on Cyclopropane Scaffolds,"[structure: see text] A practical and efficient route for the stereoselective conversion of easily accessible homoallylic alcohols to diastereomerically pure cis- and trans-disubstituted and 1,2,3-trisubstituted cyclopropanes has been developed. The diversity of structures that can be prepared and the simplicity of the overall sequence make this route ideal for extension to solid-phase synthesis techniques and ultimately combinatorial library generation.",10.1021/ol9913542,2000-02-09,0.587858732872565
Organic Process Research & Development,"Identification, Synthesis, and Comprehension of an Imidazole N-3 Regioisomeric Impurity of Olmesartan Medoxomil Key Intermediate","Trityl olmesartan ethyl ester (TOEE), a key intermediate of the launched angiotensin II receptor blocker olmesartan medoxomil, was built using two blocks via an N -alkylation reaction, wherein the imidazole N -1 isomer of this intermediate was the only isomeric product reported previously. Unexpectedly, from a sample of laboratory trials, an undesired impurity (a level of 0.2–0.3%) sharing the same molecular mass with TOEE was detected and assumed to be an N-3 regioisomeric impurity of TOEE. Accordingly, a five-step lactone ring-opening synthetic route was designed and successfully used to obtain this impurity, whose structure perfectly matched the NMR and mass spectra. Subsequent characterization by SCXRD directly confirmed the initial speculation of it being an N-3 regioisomer, which was reported for the first time. Next, two downstream impurities toward the active pharmaceutical ingredient (API) were synthesized, in which the N-3 impurity of API proved to be inseparable with the API molecule under the European Pharmacopoeia chromatography method, introducing a risk of impurity identification. Sequential investigations focusing on impurity tracing and control strategies of the downstream impurities were conducted to meet the quality control requirements.",10.1021/acs.oprd.2c00002,2022-02-18,0.5878549398834793
Journal of Organic Chemistry,"Protease-Mediated Separation of Cis and Trans Diastereomers of 2(<i>R,S</i>)-benzyloxymethyl-4(<i>S</i>)-carboxylic Acid 1,3-Dioxolane Methyl Ester:  Intermediates for the Synthesis of Dioxolane Nucleosides","Dioxolane nucleosides, in which an oxygen replaces the carbon in the 3‘ position in the ribose moiety of 2‘,3‘-dideoxy nucleosides, are powerful antiviral and anticancer drugs. However, their synthesis remains challenging since it must control the relative and absolute stereochemistry of two stereocenters in the five-membered ring. Several promising routes yield a key intermediate dioxolane as a mixture of diastereomers (epimers at the 2-position of the dioxolane), but separation of these diastereomers by silica gel chromatography is tedious and expensive. In this paper, we report that two inexpensive, commercially available proteases α-chymotrypsin and bovine pancreatic protease discriminate between the cis and trans diastereomers of 2( R,S )-benzyloxymethyl-1,3-dioxolane-4( S )-carboxylic acid methyl ester. Although hydrolysis occurs at a carboxyl group three bonds away from the 2-stereocenter, the diastereoselectivity is high ( D = 29−35, favoring trans). We discovered these selective hydrolases by screening a library of 91 commercial hydrolases with our previously developed stereoselectivity screens that use pH indicators. A small-scale α-chymotrypsin-catalyzed hydrolysis of a 2:1 mixture of cis- and trans -dioxolane methyl esters yielded the desired cis -dioxolane methyl ester in >98% diastereomeric excess and 55% overall yield (67% was the maximum possible yield). Computer modeling of transition-state analogues of both diastereomers in the active site of α-chymotrypsin suggests that stereoselectivity arises because the slow-reacting diastereomer binds in a nonproductive orientation.",10.1021/jo990757c,1999-11-19,0.5878426425997202
Organic Letters,"δ-Amino β-Keto Esters, a Designed Polyfunctionalized Chiral Building Block for Alkaloid Synthesis. Asymmetric Synthesis of (<i>R</i>)-(+)-2-Phenylpiperidine and (−)-SS20846A","[formula: see text] delta-Amino beta-keto esters 3 and 11 are designed polyfunctionalized chiral building blocks for alkaloid synthesis and are prepared in one step from the corresponding sulfinimine (N-sulfinyl imine). Concise highly enantioselective four-step syntheses of 2-phenylpiperidine (7) and SS20846A (14) from 3 and 11, respectively, are described.",10.1021/ol005580j,2000-03-23,0.5878412731442264
Journal of Organic Chemistry,General Access to Concave-Substituted <i>cis</i>-Dioxabicyclo[3.3.0]octanones: Enantioselective Total Syntheses of Macfarlandin C and Dendrillolide A,"The evolution of a strategy to access the family of rearranged spongian diterpenoids harboring a concave-substituted cis -2,8-dioxabicyclo[3.3.0]octan-3-one fragment is described. The approach involves late-stage fragment coupling of a tertiary-carbon radical and an electron-deficient double bond to form vicinal quaternary and tertiary stereocenters with high fidelity. A stereoselective Mukaiyama hydration is the key step in the subsequent elaboration of the cis -2,8-dioxabicyclo[3.3.0]octan-3-one moiety. This strategy was utilized in enantioselective total syntheses of (−)-macfarlandin C and (+)-dendrillolide A. An efficient construction of enantiopure tetramethyloctahydronaphthalenes was developed during the construction of (−)-macfarlandin C.",10.1021/acs.joc.0c02273,2020-11-16,0.5878335043752563
Organic Process Research & Development,An Improved Procedure for Preparation of Carbapenem Antibiotic:  Meropenem,"An efficient synthesis of a 1β-methyl carbapenem antibiotic, meropenem, is described. The present process does not involve cryogenic temperatures, chromatographic purification, or reverse osmosis and is amenable to large scale synthesis.",10.1021/op700088y,2007-06-15,0.587831355481275
Journal of Organic Chemistry,Synthesis of Isoquinolines and Pyridines by the Palladium/Copper-Catalyzed Coupling and Cyclization of Terminal Acetylenes and Unsaturated Imines:  The Total Synthesis of Decumbenine B,"Monosubstituted isoquinolines and pyridines have been prepared in good to excellent yields via coupling of terminal acetylenes with the tert-butylimines of o-iodobenzaldehydes and 3-halo-2-alkenals in the presence of a palladium catalyst and subsequent copper-catalyzed cyclization of the intermediate iminoalkynes. In addition, isoquinoline heterocycles have been prepared in excellent yields via copper-catalyzed cyclization of iminoalkynes. The choice of cyclization conditions is dependent upon the nature of the terminal acetylene that is employed, as only aryl and alkenyl acetylenes cyclize under the palladium-catalyzed reaction conditions that have been developed. However, aryl-, vinylic-, and alkyl-substituted acetylenes undergo palladium-catalyzed coupling and subsequent copper-catalyzed cyclization in excellent yields. The total synthesis of the isoquinoline natural product decumbenine B has been accomplished in seven steps and 20% overall yield by employing this palladium-catalyzed coupling and cyclization methodology.",10.1021/jo010579z,2001-12-12,0.5878241938337447
Journal of Organic Chemistry,"Simple and Efficient Production of (<i>Z</i>)-4-Hydroxytamoxifen, a Potent Estrogen Receptor Modulator","A McMurry coupling reaction and selective crystallization were used to develop a simple and efficient two-step synthesis of (Z)-4-hydroxytamoxifen (2a). This compound is an active metabolite of tamoxifen, a selective estrogen receptor (ER) modulator widely used to treat breast cancer. The synthesis employed 1,1-bis(4-hydroxyphenyl)-2-phenylbut-1-ene (1) as a useful building block.",10.1021/jo035164n,2003-10-30,0.587816956017917
Tetrahedron,"A short and convergent enantioselective synthesis of (3S)-2,3-oxidosqualene",,10.1016/s0040-4039(00)61710-0,1993-09-01,0.5878116605501689
Tetrahedron,Concise synthesis of a highly functionalized cyclopentane segment: toward the total synthesis of kansuinine A,,10.1016/j.tetlet.2007.06.046,2007-07-03,0.5878072524543355
Tetrahedron,Corrigendum to “New efficient pathway for the synthesis of 3-aminoestrone”,,10.1016/s0040-4039(03)00585-9,2003-04-01,0.587800784433385
Tetrahedron,New efficient pathway for the synthesis of 3-aminoestrone,,10.1016/s0040-4039(02)01823-3,2002-10-01,0.587800784433385
Synlett,"The Synthesis of a New Pyrazolo[3,4-<i>c</i>]pyridine C-Nucleoside, StructurallyRelated to Formycin B","The first preparation of the 4-deaza analogue of formycin B is described, via the reaction of 3-acetamido-2-methoxy-4-methylpyridine with a suitably protected ribonolactone and subsequent ring closure to result in the 3-substituted pyrazolo[3,4-c]pyridine riboside 12.",10.1055/s-2002-33534,2002-01-01,0.5877973753139728
Synlett,The Enantioselective Synthesis of Neopentylamine Derivatives,All articles of this category Enantiomerically pure neopentylamine derivatives 1 can be readily prepared from ketones 2 by a four step sequence involving imine formation with R- α-methylbenzylamine followed by a highly diastereoselective reduction with NaBH 4 . enantioselective - amine - imine,10.1055/s-1995-4901,1995-02-01,0.5877956926546083
Synlett,Synthesis of Novel Four-Membered Ring Amino Acids as Modulators of the<i>N</i>-Methyl-D-Aspartate(NMDA) Receptor Complex,"All articles of this category The first syntheses of three novel four-membered ring amino acids (3-aminooxetane-3-carboxylic acid, 3-aminoazetidine-3-carboxylic acid and 3-aminothietane-3-carboxylic acid), starting from 1-chloro-2,3-epoxypropane, are reported together with a summary of their biological actions at the NMDA receptor-ion channel complex.",10.1055/s-1991-20873,1991-01-01,0.5877917205853843
Organic Letters,Formal Synthesis of (+)-Nakadomarin A,"The formal synthesis of (+)-nakadomarin A was completed. The significant points of this synthesis are the highly stereoselective formation of the diazatricyclo[6.4.0.0(1,5)]dodecane skeleton (A, B, and D rings) based on the Pauson-Khand reaction and novel furan ring (C ring) formation, using the vinyl residue of the Pauson-Khand product.",10.1021/ol100412f,2010-03-16,0.5877801384358243
Angewandte Chemie International Edition,"A Stereospecific, Intermolecular Biaryl-Coupling Approach to Korupensamine A En Route to the Michellamines",,10.1002/(sici)1521-3773(19991203)38:23<3530::aid-anie3530>3.3.co;2-n,1999-12-03,0.5877785953406545
Synthesis,An Epoxide-Based Enantioselective Synthesis of the Antifungal Antibiotic (+)-Preussin,"All articles of this category The enantioselective total synthesis of (2 S ,3 S ,5 R )-1-methyl-5-nonyl-2-(phenylmethyl)-3-pyrrolidinol, (+)-preussin 1 , from ( S )-phenylalanine is described. Key steps involve ring-opening of a (1-aminoalkyl)epoxide 5 by an allyl anion, [2,3]-sigmatropic rearrangement of 9 and cyclization of aminoepoxide 11 to give the pyrrolidine unit 12 with the correct stereochemistry. amino epoxide - allyl anion - [2,3]-sigmatropic rearrangement - Sharpless epoxidation - preussin",10.1055/s-1997-1347,1997-11-01,0.5877729695189564
Synlett,Total Synthesis of Horsfiline: A Palladium-Catalyzed Domino Heck-Cyanation Strategy,"A total synthesis of horsfiline (I) has been accomplished featuring a key intramol. palladium-catalyzed domino Heck-cyanation sequence for the formation of the 3,3'-disubstituted oxindole. [on SciFinder (R)]",10.1055/s-0029-1218004,2009-10-08,0.5877657520978226
European Journal of Organic Chemistry,Synthesis of an (±)‐Estrone Precursor: The Scope of Zr‐ and Co‐Mediated Cycloannulations,Abstract The synthesis of an estrone intermediate based on a new approach was studied. The construction of the basic framework was carried out in three steps from a simple styrene derivative. The crucial reaction sequence for the steroid skeleton construction relied on a Zr‐mediated cyclization (Zr‐ene reaction)/propargylation followed by a Co‐mediated diastereoselective Pauson–Khand reaction that afforded various D ‐ring‐substituted tetracyclic ketones 11 with natural trans ‐ anti stereochemistry. The conjugated addition reaction of Me 2 CuLi to tetracyclic ketone 11a aiming at the installation of the angular methyl group in the 13‐position gave rise exclusively to product 12 with unnatural trans‐anti‐cis stereochemistry The successful synthesis of known estrone intermediate 4 with natural trans‐anti‐trans stereochemistry was accomplished by chemoselective reduction of the carbonyl group of ketone 11b . Attempts to use other metallo‐ene reactions to affect the synthesis of steroid B‐ring are also described.,10.1002/ejoc.200900937,2009-12-18,0.587755183557532
Journal of the American Chemical Society,Stereoselective Total Syntheses and Reassignment of Stereochemistry of the Freshwater Cyanobacterial Hepatotoxins Cylindrospermopsin and 7-Epicylindrospermopsin,"A stereoselective total synthesis of the structure 1 proposed for the freshwater cyanobacterial heptatotoxin cylindrospermopsin has been accomplished in approximately 30 operations starting from commercially available 4-methoxypyridine. Utilizing methodology developed by Comins, the tetrasubstituted piperidine A-ring unit of the hepatotoxin was efficiently constructed. The two remaining stereocenters in the natural product were then set by a stereospecific intramolecular N-sulfinylurea Diels-Alder cyclization/Grignard ring opening/allylic sulfoxide [2,3]-sigmatropic rearrangement sequence previously developed in these laboratories, leading to key intermediate 29. The stereochemical assignment of alcohol 29, which contains all six of the stereogenic centers of the natural product, was confirmed by an X-ray crystal structure determination of a derivative. Installation of the D-ring uracil moiety was effected by using our new methodology developed for this purpose, and construction of the C-ring guanidine completed the total synthesis of racemic structure 1. However, the (1)H NMR data for this compound do not match that of cylindrospermopsin, but instead agree with the data reported for 7-epicylindrospermopsin, a minor toxic metabolite that co-occurs with cylindrospermopsin. Therefore, we propose a revision of the stereochemical assignments of these natural products such that cylindrospermopsin is now represented as structure 2 and 7-epicylindrospermopsin is 1. This reassignment was further confirmed by Mitsunobu inversion of the C-7 alcohol 51 to epimer 52, and conversion of this compound to tetracyclic diol 57, which has previously been transformed to cylindrospermopsin (2).",10.1021/ja020032h,2002-03-22,0.5877541422542436
Tetrahedron,A convenient synthetic route for alkynylselenides from alkynyl bromides and diaryl diselenides employing copper(I)/imidazole as novel catalyst system,,10.1016/j.tetlet.2008.06.071,2008-06-20,0.5877528034992213
Journal of Organic Chemistry,Synthesis of (±)-Gymnomitrol. Mn(OAc)<sub>3</sub>-Initiated Free-Radical Cyclization of Alkynyl Ketones,Mn(OAc)(3)-initiated cyclization of alkynyl ketones in 9-19:1 EtOH/HOAc at 90 degrees C is a useful cyclization procedure in favorable cases. Cyclization of (trimethylsilyl)alkynyl ketone 4e provides 62% of silylalkenes 26 and 27 in the key reaction of a seven-step (16% overall yield) synthesis of gymnomitrol (1) from readily available ketone 23. 9alpha-Hydroxygymnomitryl acetate (2) and 9-oxogymnomitryl acetate (3) have been prepared from gymnomitrol. Cyclization of propargyl cyclohexanones 39a-c provides bicyclic compounds 40-42 in 40-60% yield.,10.1021/jo9622338,1997-04-01,0.5877439731387909
Tetrahedron,Chiral ring a synthons for vitamin d synthesis,,10.1016/s0040-4039(01)90995-5,1984-01-01,0.5877430831527102
Tetrahedron,Fragmentations and rearrangements of 22-hydroxyl substituted milbemycins - synthesis of a key lactone intermediate,,10.1016/0040-4039(94)85224-3,1994-04-01,0.587739714779737
Journal of Organic Chemistry,"Diastereoselective Synthesis of γ-Amino-δ-hydroxy-α,α-difluorophosphonates: A Vehicle for Structure−activity Relationship Studies on SMA-7, a Potent Sphingomyelinase Inhibitor","A highly diastereoselective synthesis of 2-amino alcohol derivatives bearing a difluoromethylphosphonothioate group at the 3-position was achieved through LiAlH(O-t-Bu)(3)-mediated reduction of the corresponding alpha-amino ketones. The phosphonothioate moiety of the product was readily converted into the corresponding phosphonate by oxidation with m-CPBA, followed by aqueous workup. The developed methods should be useful for SAR studies of SMA-7, a potent inhibitor of SMases.",10.1021/jo9008782,2009-07-17,0.5877370984436067
Angewandte Chemie International Edition,Short and Efficient Syntheses of Protoberberine Alkaloids using Palladium‐Catalyzed Enolate Arylation,"A concise synthesis of the biologically active alkaloid berberine is reported, and a versatile palladium-catalyzed enolate arylation is used to form the isoquinoline core. The overall yield of 50 % is a large improvement over the single, previous synthesis. By design, this modular route allows the rapid synthesis of other members of the protoberberine family (e.g., pseudocoptisine and palmatine) by substitution of the readily available aryl bromide and ketone coupling partners. Moreover, by combining enolate arylation with in situ functionalization, substituents can be rapidly and regioselectively introduced at the alkaloid C13 position, as demonstrated by the total synthesis of dehydrocorydaline. The avoidance of electrophilic aromatic substitution reactions to make the isoquinoline allows direct access to analogues possessing more varied electronic properties, such as the fluorine-containing derivative synthesized here.",10.1002/anie.201409164,2014-10-27,0.5877321843751931
Tetrahedron,Facile and efficient total synthesis of (±)-cryptotanshinone and tanshinone IIA,,10.1016/s0040-4039(03)00191-6,2003-03-01,0.5877304889517122
Tetrahedron,"A novel highly stereoselective total synthesis of epothilone B and of its (12R,13R) acetonide",,10.1016/s0040-4039(00)01318-6,2000-09-01,0.587728740132024
Synthesis,Synthesis of Fluorinated Imines by Addition of Fluoroalkyl Radicals to Conjugated Imines,"A novel preparation of β-perfluoroalkyl imine derivatives, useful as synthetic building blocks, was achieved by a route involving addition of electrophilic fluoroalkyl radicals to α,β-unsaturated imines.",10.1055/s-0029-1218755,2010-04-23,0.5877282356673416
Journal of the American Chemical Society,Dearomative Synthetic Entry into the Altemicidin Alkaloids,"-derived monoterpene alkaloids possess dense, highly polar azaindane cores as well as potent cytotoxic and tRNA synthetase inhibitory properties. The congested α-amino acid motif decorating their presumed iridoid-like core structure has proven to be both a synthetic challenge and a biosynthetic mystery to date. Herein, we report a distinct, abiotic strategy to these alkaloids resulting in a concise synthesis of altemicidin from simple chemical feedstocks. Key chemical findings include the exploitation of a dearomative pyridinium addition and dipolar cycloaddition sequence to stereospecifically install the quaternary amine moiety, and a chemoselective molybdenum-mediated double reduction to establish the fully functionalized azaindane nucleus with minimal redox manipulations.",10.1021/jacs.1c04147,2021-05-21,0.5877230057266462
Tetrahedron,"Regio- and stereoselective photo-oxygenation of (+)-11,12-diacetoxydrim-8-ene; an efficient synthesis of a key intermediate for drimane-related sesquiterpenes",,10.1016/s0040-4039(01)80636-5,1989-01-01,0.5877228375074928
Tetrahedron,Preparation of a cyclohexanone intermediate for synthesis of thromboxane antagonists,,10.1016/s0040-4039(01)93441-0,1989-01-01,0.5877156346480374
Organic Letters,Total Synthesis and Configurational Validation of (+)-Phorbaside A,"The configurational assignment of the cytotoxic marine macrolide phorbaside A has been verified by the stereodefined synthesis of the proposed structure 1 and its (18S,19R)-diastereomer 3, followed by correlation using circular dichroism spectroscopy. This first total synthesis, which proceeds in 8.2% yield over 23 steps, features two 1,4-syn boron aldol reactions, a Sonogashira coupling, and an alpha-glycosylation to append the L-evalose sugar moiety.",10.1021/ol100693c,2010-04-13,0.5877151462115929
Journal of the American Chemical Society,Total Synthesis of Asimicin via Highly Stereoselective [3 + 2] Annulation Reactions of Substituted Allylsilanes,"A highly stereoselective total synthesis of (+)-asimicin (1) is reported. The synthesis features two chelate-controlled [3 + 2] annulation reactions-one of which (e.g., 2 + 3) constitutes a key, convergent fragment assembly step-that establish all of the stereochemistry of the bis-tetrahydrofuran unit of the natural product.",10.1021/ja051986l,2005-07-13,0.5877136104499241
Organic Letters,"Copper(I)-Catalyzed Ketone, Amine, and Alkyne Coupling for the Synthesis of 2-Alkynylpyrrolidines and -piperidines","A Cu(I)-catalyzed coupling of a ω-chloro ketone, a primary amine, and an alkyne is described. This protocol allows for the synthesis of α-quaternary carbons in 2-alkynyl-substituted N-heterocycles. The key step is the in situ generation of a cyclic ketiminium species, which has enhanced reactivity for alkynylation compared to acyclic ketiminium species.",10.1021/acs.orglett.6b02127,2016-09-13,0.5877133944835718
Tetrahedron,Toward the synthesis of taxol and its analogs: Incorporation of non-aromatic C-rings in the pinene pathway,"An approach to the taxane skeleton based on the elaboration of the terpene pinene is described. In this approach, the pinene oxidation product verbenone (2) was converted in 5 steps into the allylic alcohol 4, a compound containing a non-aromatic taxane C-ring precursor. The dianionic cyclization of 4 to yield the tetracycles 5a and 5b is described along with the elaboration of these compounds to the taxane tricycle 6. An efficient samarium diiodide-mediated reduction involving tricycle 6 yields an advanced taxane precursor with an sp3 center at the C8 position.",10.1016/0040-4039(95)00897-l,1995-07-01,0.5876983798994583
Tetrahedron,Two key biogenetic intermediates of Cephalotaxus alkaloids from Cephalotaxus oliveri and C. lanceolata,,10.1016/j.tetlet.2016.10.026,2016-10-12,0.5876975921154527
Synthesis,A Novel Synthesis of<i>N</i>-(2-Alkynyl)arylamines,"All articles of this category A new general one-pot method for the high yield synthesis of secondary N -(2-alkynyl)arylamines by reaction of N -(methoxymethyl)arylamines and 1-alkynyllithium is described. This procedure has successfully been extended to the preparation of symmetrically and non-symmetrically substituted 2-butyne-1,4-diamines.",10.1055/s-1989-27137,1989-01-01,0.5876913957809401
Journal of Organic Chemistry,Synthesis of Pharmacologically Relevant Indoles with Amine Side Chains via Tandem Hydroformylation/Fischer Indole Synthesis,"[reaction: see text] The sequence of hydroformylation and Fischer indole synthesis starting from amino olefins and aryl hydrazines is described. In a convergent manner, the two units bearing pharmacologically relevant substituents are assembled in the final indolization step. This modular and diversity-oriented approach to tryptamines and homotryptamines can be conducted in water and allows synthesis of branched and nonbranched tryptamines as well as tryptamine-based pharmaceuticals such as the 5-HT1D agonist L 775 606.",10.1021/jo050464l,2005-06-14,0.5876901306221559
Synthesis,Simple Three-Step Synthesis of (<i>R</i>)- and (<i>S</i>)-4-Amino-3-hydroxybutanoic Acid (GABOB) by Stereoselective Aldol Addition,"All articles of this category A simple synthesis of both ( R )- and ( S )-GABOB (5) is reported. In the key step, doubly deprotonated ( R )- or ( S )-2-Hydroxy-1,2,2-triphenylethyl acetate (HYTRA) (1) is added to Cbz-protected glycinal ( 2) .",10.1055/s-1989-27410,1989-01-01,0.5876871665724565
Organic Letters,"The Total Synthesis of (−)-7-Deoxyloganin via <i>N</i>-Heterocyclic Carbene Catalyzed Rearrangement of α,β-Unsaturated Enol Esters","The diastereoselective N-heterocyclic carbene (NHC) catalyzed rearrangement of α,β-unsaturated enol ester (S)-2b has been used to assemble dihydropyranone (S)-3b, a material embodying the bicyclic core of the iridoid family of natural products. Elaboration of this intermediate, by chemoselective reduction followed by stereoselective β-glycosylation, has allowed the total synthesis of (-)-7-deoxyloganin (1) to be achieved in four subsequent steps.",10.1021/ol101983h,2010-09-28,0.5876776915759184
Organic Letters,Total Synthesis of Dysoxylactam A,"The total synthesis of a potent multi-drug-resistant reverser, dysoxylacatam A ( 1 ), was achieved in a highly efficient and stereocontrolled fashion. The highlights of the strategy enlisted an iterative combination of lithiation–borylation tactics including Aggarwal homologation and Matteson homologation, Brown crotylation, Krische allylation, and ring-closing metathesis to forge the macrocycle.",10.1021/acs.orglett.0c00074,2020-02-12,0.5876733535118183
Tetrahedron,A highly refined version of the α-keto ester based carbapenem synthesis: The total synthesis of meropenem,,10.1016/s0040-4039(98)01523-8,1998-09-01,0.5876608434703547
Organic Letters,"Reductive CO<sub>2</sub> Fixation via the Selective Formation of C–C Bonds: Bridging Enaminones and Synthesis of 1,4-Dihydropyridines","Herein, a selective tandem C–C bond-forming reaction with CO 2 was developed to realize the bridging of enaminones and synthesis of 1,4-dihydropyridines, respectively. n -Butylamine significantly promoted this CO 2 deoxymethylenation procedure catalyzed by 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) and ZnCl 2 . The mechanism involving the formation of bis(silyl)acetal, nucleophilic addition, and amine elimination was also interpreted to clarify the bridging of two molecules of enaminones with CO 2 and the generation of dihydropyridine derivatives.",10.1021/acs.orglett.0c02963,2020-10-12,0.5876592577457452
Journal of the American Chemical Society,"Construction of Arene-Fused-Piperidine Motifs by Asymmetric Addition of 2-Trityloxymethylaryllithiums to Nitroalkenes:  The Asymmetric Synthesis of a Dopamine D1 Full Agonist, A-86929","The straightforward methodology for the construction of chiral arene-fused-piperidine motifs using a highly enantioselective addition of 2-trityloxymethylaryllithiums to cyclic and acyclic nitroalkenes has been developed. The versatility of the process was highlighted by the first asymmetric synthesis of a dopamine D1 full agonist, A-86929.",10.1021/ja031760n,2004-01-30,0.5876508008870573
Journal of Organic Chemistry,"Enantioselective Synthesis of 3,3-Difluoropyrrolidin-4-ol, a Valuable Building Block in Medicinal Chemistry","In this paper, we report for the first time two enantioselective routes to 4,4-difluoropyrrolidin-3-ol, a valuable building block in medicinal chemistry. In the first route, we took advantage of the C2 symmetry of (3R,4R)-3,4-dihydroxypyrrolidine in which the desired chirality was derived from the chiral pool (l-(+)-tartaric acid). In the second route, we efficiently assembled the pyrrolidine ring in the presence of a gem-difluoro moiety to avoid using potentially hazardous deoxofluorinating reagents and subsequently introduced the chirality by a stereoselective iridium-diamine-catalyzed asymmetric transfer hydrogenation reaction.",10.1021/acs.joc.6b00305,2016-05-03,0.5876454816896399
Tetrahedron,Trans hydrindanes by dimide reduction: Synthesis of dihydro-B-nortestosterone and its 17α-methyl derivative,,10.1016/0040-4039(96)01328-7,1996-08-01,0.5876417410529486
Angewandte Chemie International Edition,"Enantioselective Synthesis of 1,2‐Diarylaziridines by the Organocatalytic Reductive Amination of α‐Chloroketones","One-sided triangles: A simple protocol has been developed for the synthesis of highly useful single enantiomers of 1,2-diarylaziridines. The method involves conversion of the readily available α-chloroacetophenones into the corresponding imines, followed by an enantioselective reduction with Cl3SiH catalyzed by the L-valine-derived formamide L* and ring closure to give the desired aziridines (see scheme).",10.1002/anie.200700165,2007-04-05,0.5876355715801567
European Journal of Organic Chemistry,A Direct Palladium‐Catalyzed Route for the Synthesis of Benzo[<i>a</i>]carbazoles through Sequential C–C Bond Formation and C–H Bond Functionalization,Abstract A direct palladium‐catalyzed route for the synthesis of novel benzo[ a ]carbazoles through sequential C–C bond formation and C–H bond functionalization by using readily available starting materials has been demonstrated. Prominent among the advantages of this new method are operational simplicity and good yields.,10.1002/ejoc.201101401,2011-11-24,0.5876305341485013
Organic Letters,"Synthesis of the Unnatural Amino Acid AGDHE, a Constituent of the Cyclic Depsipeptides Callipeltins A and D","[reaction: see text] The novel amino acid residue (2R,3R,4S)-4-amido-7-guanidino-2,3-dihydroxyheptanoic acid (AGDHE, 3), a constituent of the cyclic depsipeptides callipeltins A and D, and its (2S,3S,4S) diastereomer were synthesized from a protected L-ornithine derivative in 13 steps (15% overall yield), and its configurational assignment was reexamined by (1)H NMR.",10.1021/ol0269852,2002-11-16,0.5876293675981483
Tetrahedron,MMTr as an efficient anomeric S-protecting group for the synthesis of glycosyl thiols,,10.1016/j.tetlet.2006.09.003,2006-09-21,0.5876216671968019
Journal of Organic Chemistry,Absolute Configuration of Anti-HIV-1 Agent (−)-Concentricolide: Total Synthesis of (+)-(<i>R</i>)-Concentricolide,"The first enantioselective total synthesis of (+)-(R)-concentricolide, the enantiomer of an anti-HIV-1 agent isolated from Daldinia concentrica, from 2-iodophenol in 7 steps reveals the (S)-configuration for the natural form of the furanophthalide. The key features include an anionic ortho-Fries rearrangement to furnish 3-iodosalicylamide, facile construction of the benzofuran system employing the tandem Sonogashira coupling annulation reaction, directed ortho metalation to introduce a propanoyl group, as well as CBS reduction, establishing the stereocenter enantioselectively.",10.1021/jo2004132,2011-04-04,0.5876192602435905
Tetrahedron,A single-step synthesis of 4-hydroxycyclopentenones from 3-Ethoxycarbonyl-2-oxo-propylidenetriphenylphosphorane and glyoxals,,10.1016/s0040-4039(00)74103-7,1993-07-01,0.587617835169846
Tetrahedron,"Single-step synthesis of cyclopentenones from (3-alkoxycarbonyl-2-oxo-propylidene)triphenylphosphorane and 1,2-diacylethylenes",,10.1016/0040-4039(95)02186-8,1996-01-01,0.587617835169846
Synthesis,"An Improved Synthesis of Chiral 2,2′-Bipyridine Ligand C3-ACBP Without Column Chromatography","Abstract A method for purifying compounds bearing pyridine structure from Mitsunobu reaction mixtures using zinc chloride and releasing bipyridines from Ullmann coupling reaction mixtures by using sulfide anion for competitively coordinating the copper ion were developed for the facile synthesis of the chiral 2,2′-bipyridine ligand (Ra ,S,S)-C3-ACBP. With these improvements, an improved synthesis of the chiral ligand at a 7 gram scale has been fulfilled in 48% overall yield without column chromatography within 3–4 days.",10.1055/a-2063-1330,2023-03-27,0.587615314298814
European Journal of Organic Chemistry,Asymmetric Synthesis of the C1–C16 Segment of Lasonolide A,The C1–C16-segment of lasonolide A has been prepared stereoselectively in high chemical and optical yield starting from 2α-methyl-8-oxabicyclo[3.2.1]oct-6-en-3-one (rac -1).,10.1002/(sici)1099-0690(199911)1999:11<2991::aid-ejoc2991>3.0.co;2-z,1999-11-01,0.5876079745158037
European Journal of Organic Chemistry,Asymmetric Synthesis of the C1–C16 Segment of Lasonolide A,The C1–C16-segment of lasonolide A has been prepared stereoselectively in high chemical and optical yield starting from 2α-methyl-8-oxabicyclo[3.2.1]oct-6-en-3-one (rac -1).,10.1002/(sici)1099-0690(199911)1999:11<2991::aid-ejoc2991>3.3.co;2-q,1999-11-01,0.5876079745158037
Journal of the American Chemical Society,Total Syntheses of (+)-Lyconadin A and (−)-Lyconadin B,"The enantioselective syntheses of (+)-lyconadin A and (−)-lyconadin B are described. Key bond constructions include a strategy-level intramolecular aldol/conjugate addition cascade, an olefin aminoiodination, and a novel one-pot α-pyridinone annulation.",10.1021/ja070336+,2007-03-17,0.5876060584687905
Tetrahedron,"A regioselective synthesis of 4,5- and 4,8- disubstitutedaza-anthraquinones by the diels-alder route",,10.1016/s0040-4039(00)82224-8,1988-01-01,0.5876059282124008
Tetrahedron,"Synthesis of δ-lactone, oxetane and azetidinone analogs from the naturally occurring β-lactone L-659,699. The preparation of a novel HMG CoA synthase inhibitor.",,10.1016/s0040-4039(00)92700-x,1991-07-01,0.5876046649597034
Organic Letters,"A Concise, Biomimetic Total Synthesis of (+)-Davanone","A concise, biomimetic synthesis of the antifungal and antispasmodic natural product (+)-davanone is described. The key stereoselective reactions are a Sharpless asymmetric epoxidation, a thiazolium-catalyzed esterification, and a palladium-mediated cyclization. All carbons are derived from isoprene units and no protecting groups are used, permitting an atom- and redox-economical synthesis.",10.1021/ol900697w,2009-04-14,0.5876046422333414
Synlett,Stereoselective Synthesis of the Brassinolide Side Chain by the Use of a 5-Exo-α-Silyl Radical Cyclization - Protiodesilylation Sequence,"All articles of this category The stereoselective synthesis of the steroid having the brassinolide side chain 2 has been achieved from readily available aldehyde 7 in 8 steps and 31% overall yield, featuring a 5-exo-mode of α-silyl radical cyclization - protiodesilylation sequence as a means for the key stereoselective installment of the 24-methyl group. brassinolide side chain - α-silyl radical cyclization - 5-exo-radical cyclization - 1-sila-2-oxacyclopentane - protiodesilylation",10.1055/s-1995-5095,1995-08-01,0.5875979141509226
Organic Letters,Improved Synthesis of the Epoxy Isoprostane Phospholipid PEIPC and its Reactivity with Amines,"An improved synthesis of the naturally occurring hydroxy ketone 1-palmitoyl-2-(5,6)-epoxyisoprostane E 2- sn-glycero-3-phosphocholine (PEIPC) 1, a compound that plays a role in endothelial activation in atherosclerosis, has been carried out using a PMB ether as the key protecting group. Opening of an intermediate with pentylamine shows that the allylic epoxide is the position of attack by nucleophiles.",10.1021/ol8014804,2008-08-28,0.5875950818384064
Angewandte Chemie International Edition,Nickel/Copper‐Cocatalyzed Asymmetric Benzylation of Aldimine Esters for the Enantioselective Synthesis of α‐Quaternary Amino Acids,"Abstract The first asymmetric Ni/Cu cocatalyzed benzylation of aldimine esters is reported. A series of benzyl‐substituted α‐quaternary amino acids could be synthesized in high yield and with high levels of enantioselectivity (up to 90 % yield and 99 % ee). The experimental and theoretical calculation results suggested that the strong electrophilicity of the η 3 ‐benzylnickel intermediate is crucial for the high reactivity, enabling the reaction under base‐free conditions. Furthermore, this method has been applied to the synthesis of the cell adhesion inhibitor BIRT‐377 analogues, and the key intermediate of the NK1 receptor antagonist PD154075 and CCK‐B receptor antagonist CI‐988.",10.1002/anie.202203448,2022-03-23,0.587593734131625
Organic Process Research & Development,An Improved Preparation Process for Gemcitabine,"An improved, cost-effective, and convenient process, using cinnamoyl as hydroxyl protective group and tosyl as the leaving group for gemcitabine ( 1 ) is described. The overall yield obtained from this newly developed process is around 10%, including two stereospecific crystallizations, and the quality of the product complies with the requirements of USP30.",10.1021/op800104r,2008-08-21,0.5875898857108462
Angewandte Chemie International Edition,Total Synthesis of (−)‐Dendrobine,Cascading to alkaloids: an 18-step total synthesis of (-)-dendrobine is based on a reaction cascade with a key amine group. The amine is the initiator of the cascade and provides an efficient method for installing the stereocenters at C11 and C3. The overall transformation occurs stereoselectively only when the conversion is carried out without the isolation of intermediates.,10.1002/anie.201108564,2012-02-17,0.58758813259036
Tetrahedron,"The chiral specific synthesis of DMP 754, a platelet GP antagonist",,10.1016/0040-4039(96)00694-6,1996-06-01,0.5875861614433739
Green Chemistry,"A chemical–electrochemical cascading strategy for the efficient synthesis of 2,5-furandicarboxylic acid and its methyl ester from 2-furoic acid and CO <sub>2</sub>",The electrocatalytic upgrading of biomass-derived furanics offers a sustainable route to high-value monomers for polymer manufacturing.,10.1039/d5gc05661f,2025-12-17,0.5875851436191627
Synlett,"An Easy Route to Acylfurans and Dihydrofurans by Intramolecular Cyclization of Substituted 1,3-Diketones","All articles of this category The synthesis of 3-acylfurans 5 and 4-acyl-2,3-dihydrofurans 6 is achieved by intramolecular cyclization of 2-(2-alkynyl or 2-alkenyl)-substituted 1, 3-diketones 3 and 4 prepared from 4-amino-1-azabutadienes. The reaction, which involves either an exo-dig or exo-trig ring closure, is promoted by polyphosphoric acid.",10.1055/s-1990-21206,1990-01-01,0.5875843891562086
Synlett,"2,6-Difunctionalization of N-Substituted Dithienothiazines via Dilithiation","The regioselective lithiation of dithienothiazines followed by electrophilic trapping in a one-pot fashion is an efficient route to 2-mono- and 2,6-difunctionalized dithienothiazines. A pseudo five-component dilithiation–diformylation–double-Wittig olefination sequence gives a dithienothiazine symmetrically functionalized with α,β-unsaturated ester side chains in excellent yield.",10.1055/s-0033-1340307,2013-11-13,0.5875828257225146
Tetrahedron,Efficient convergent synthesis of a trans-fused 6-6-6-6-membered tetracyclic ether ring system,,10.1016/s0040-4039(99)02173-5,2000-02-01,0.5875800498941919
Journal of Organic Chemistry,Convergent Total Synthesis of (+)-Mycalamide A,"The details of a convergent total synthesis of (+)-mycalamide A are described. Yb(OTf)3-TMSCl-catalyzed cross-aldol reaction conditions are used to synthesize the right segment of mycalamide A. In this reaction, an acid-sensitive aldehyde reacts with methyl trimethylsilyl dimethylketene acetal without epimerization to provide the desired aldol adduct. Additionally, a tetrahydropyran ring, which is the left segment of mycalamide A, is prepared using a novel one-pot delta-lactone formation methodology. Both segments are constructed from a common starting material, d-mannitol. These segments are then coupled in the presence of BuLi, and the functional groups are transformed to complete the synthesis of (+)-mycalamide A.",10.1021/jo060803q,2006-08-04,0.5875742257408256
Tetrahedron,Resolution during total synthesis of reserpine,,10.1016/s0040-4039(01)82761-1,1959-01-01,0.5875718298955607
Angewandte Chemie International Edition,General and Efficient Copper‐Catalyzed Three‐Component Coupling Reaction towards Imidazoheterocycles: One‐Pot Synthesis of Alpidem and Zolpidem,"Three is not a crowd: A method for the construction of imidazopyridine, imidazoquinoline, and imidazoisoquinoline frameworks has been developed. The synthetic utility of this method was demonstrated in a highly efficient one-pot synthesis of the drugs alpidem and zolpidem (see scheme).",10.1002/anie.200907291,2010-03-08,0.5875716769289334
Journal of Organic Chemistry,Modified Julia–Kocienski Reagents for a Stereoselective Introduction of Trisubstituted Double Bonds: A Formal Total Synthesis of Limazepine E and Barmumycin,"A formal total synthesis of pyrrolo[1,4]benzodiazepine anticancer antibiotic family member limazepine E is described. The synthesis features a stereoselective introduction of a trisubstituted double bond using novel sterically demanding Julia-Kocienski reagents, allowing the number of linear steps to be significantly reduced. The potential of the newly developed reagents has also been demonstrated by the formal total synthesis of barmumycin.",10.1021/acs.joc.8b00643,2018-04-11,0.5875702257736847
Organic Process Research & Development,Early Process Development and Scale-up of a Tetrazole-Containing Soluble Guanylate Cyclase Stimulator,"This paper describes the research and development of a practical and efficient process for manufacturing a soluble guanylate cyclase stimulator, 1 . The newly developed process includes an efficient telescoped process consisting of four consecutive reactions: tetrazole formation, difluoromethylation of a tetrazole moiety, deprotection, and tert -butyldiphenylsilyl (TBDPS) protection. Although regioselectivity in difluoromethylation of the tetrazole moiety was moderate, the selective TBDPS protection gave the desired regioisomer exclusively. We addressed safety issues related to thermally unstable tetrazole compounds and developed a safe process based on the thermal analysis results in which operating temperatures were controlled and the dangerous compounds were not isolated. Notably, the need for chromatographic purifications was avoided for all synthetic steps. This highly efficient and safe process was successfully demonstrated on a pilot scale to yield 24.6 kg of 1 with high quality. Overall yield was improved from 35% by the medicinal chemistry route to 45%.",10.1021/acs.oprd.5c00178,2025-08-18,0.587568303387982
Tetrahedron,Synthesis of a new bifunctional chelating agent for samarium complexation,,10.1016/j.tetlet.2003.12.073,2004-01-16,0.5875610163757701
Organic Letters,Asymmetric Synthesis of the Pentacyclic Framework of <i>Kopsia</i> Alkaloids,"High Resolution Image Download MS PowerPoint Slide Pyrroloazocine alkaloids from the Kopsia genus exhibit structural complexity and pharmacological potential. We report the concise and asymmetric synthesis of a pentacyclic core from l -proline. The key features include a C–N–C chirality transfer process to prepare the α-tertiary amine intermediate enantioselectively, an eight-membered C ring-forming Friedel–Crafts reaction at the indole C3 position, and a dearomative indole–Claisen rearrangement to form a bridged pentacyclic scaffold. This study provides a versatile platform for the divergent synthesis of diverse Kopsia alkaloids.",10.1021/acs.orglett.5c03771,2025-09-28,0.587557573540811
Journal of Organic Chemistry,"An Improved Synthesis of 4-<i>O</i>-Benzoyl-2,2-difluorooleandrose from <scp>l</scp>-Rhamnose. Factors Determining the Synthesis of 2,2-Difluorocarbohydrates from 2-Uloses","4- O -Benzoyl-2,2-difluorooleandrose ( 16 ) has been synthesized from l -rhamnose. The key steps are the formation of a difluoromethylene group in 12 by reacting ulose 11 with DAST and the chemoselective methylation of diol 13 to give compound 14 . To obtain the 2,2-difluoro compound 12, the substituents in the neighborhood of the carbonyl group in ulose 11 must be equatorial and the sugar ring must have restricted conformational mobility. This was done using 1,1,2,2-tetramethoxycyclohexane (TMC) to protect the hydroxyls at positions 3 and 4 in the sugar ring.",10.1021/jo971846x,1998-03-12,0.5875551752338767
Synlett,"A Short Synthetic Route to Novel, Highly Soluble 3,8-Dialkyl-4,7-dibromo-1,10-phenanthrolines","All articles of this category A short and convenient synthesis of highly soluble 3,8-dialkyl-4,7-dibromo-1,10-phenanthrolines is described. These compounds are versatile key building blocks for the preparation of macrocyclic oligophenanthrolines with exo -coordination sites. phenanthroline - cyclization - bromination - Heck reaction",10.1055/s-1997-1525,1997-09-01,0.5875523828965702
European Journal of Organic Chemistry,One‐Pot Preparation of Chiral Carbacycles from Morita–Baylis–Hillman Carbonates by an Asymmetric Allylic Alkylation/Olefin Metathesis Sequence,"Abstract An operationally simple, one‐pot synthetic protocol for the formation of all‐carbon, highly substituted five‐ and six‐membered rings is described. In this two‐step procedure, an asymmetric allylic alkylation (AAA) of Morita–Baylis–Hillman (MBH) carbonates with allylmalononitrile, catalyzed by a chiral tertiary amine, is followed by a ring‐closing alkene metathesis (RCM) reaction. Products are obtained in high yields, and an excellent level of optical purity of some of the target compounds is achieved after just a single recrystallization.",10.1002/ejoc.201402899,2014-09-09,0.5875478708498247
European Journal of Organic Chemistry,"Total Synthesis of (+)‐Phenguignardic Acid, a Phytotoxic Metabolite of <i>Guignardia bidwellii</i>","Abstract (+)‐Phenguignardic acid, a phytotoxic metabolite of the grape black rot fungus Guignardia bidwellii was synthesized, as well as its enantiomer, in eight steps from ( R )‐phenyllactic acid and 3‐phenylprop‐2‐yn‐1‐ol. The formation of the carboxylate at a late stage, to avoid enolization of the precursor used in the central acetalization step, proved to be crucial. The synthesis of the natural product allowed the unabiguous assignment of its hitherto unknown absolute configuration.",10.1002/ejoc.201300531,2013-07-24,0.5875450618523075
Journal of Organic Chemistry,"Preparation of CF<sub>3</sub>-Containing 1,3-Di- and 1,1,3-Trisubstituted Allenes","Novel synthetic pathway to access trifluoromethylated allenes with 1,3-di- as well as 1,1,3-trisubstitution patterns was developed from a variety of 4,4,4-trifluorobut-2-yn-1-ols which were then transformed into the corresponding vinylic iodides in highly regio- and stereospecific manners, and zinc-mediated beta-elimination after trifluoroacetylation of the hydroxyl group eventually realized the formation of the target molecules in good to excellent overall yields in facile and short steps.",10.1021/jo060909l,2006-07-11,0.5875432776939492
Organic Letters,A Unified Strategy To Construct the Tetracyclic Ring of Calyciphylline A Alkaloids: Total Synthesis of Himalensine A,"The synthetic approach to the core framework of the calyciphylline A-type Daphniphyllum alkaloids and total synthesis of himalensine A were described herein. Nitrone-induced 1,3-dipolar [3 + 2] cycloaddition was applied for the construction of A/C rings along with the all-carbon quaternary center. Pd-catalyzed enolate alkenylation and ring closing metathesis (RCM) were adopted to install the B/D rings to accomplish the [6,6,5,7] core framework. Nazarov reaction was utilized to install the F ring to complete the total synthesis of himalensine A.",10.1021/acs.orglett.9b01184,2019-04-30,0.5875411210626492
Tetrahedron,"Enantiopure 2,3-dihydro-4-pyridones as synthetic intermediates: asymmetric synthesis of 1-deoxynojirimycin",,10.1016/s0040-4039(01)01432-0,2001-09-01,0.5875368500082687
Organic Letters,A Convergent Synthesis of the Macrocyclic Core of Cytotrienins:  Application of RCM for Macrocyclization,"[reaction: see text] The asymmetric synthesis of the fully elaborated macrocyclic core of cytotrienins A-D, potent apoptosis-inducing agents, is described. Synthetic highlights include the construction of the aniline bond using a copper-mediated amidation and the use of a ring-closing metathesis (RCM) reaction to efficiently install the (E,E,E)-triene and simultaneously construct the macrocyclic lactam.",10.1021/ol036284k,2004-01-16,0.587528401557385
Journal of Organic Chemistry,"Synthesis of <i>trans</i>-3,4-Dimethyl-4-(3-hydroxyphenyl)piperidine Opioid Antagonists:  Application of the <i>Cis</i>-Thermal Elimination of Carbonates to Alkaloid Synthesis","Improved syntheses of twotrans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine opioid antagonists from 1,3-dimethyl-4-piperidinone are described. The 1,3-dimethyl-4-arylpiperidinol 23 was selectively dehydrated in a two step process to the 1,3-dimethyl-4-aryl-1,2,3,6-tetrahydropyridine 26 by the cis-thermal elimination of the corresponding alkyl carbonate derivative at 190 degrees C. In the presence of a basic nitrogen, the success of the elimination was found to be critically dependent upon the nature of the carbonate alkyl group, with Et, i-Bu, and i-Pr being preferred (90% yield). Alkylation of the metalloenamine, formed by deprotonation of 26 with n-BuLi, proceeded regio- and stereospecifically to give the trans-3,4-dimethyl-4-aryl-1,2,3,4-tetrahydropyridine 27, which was converted in three steps to the common intermediate, (3R,4R)-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine. LY255582, a centrally-active opioid antagonist, and LY246736-dihydrate, a peripherally-active opioid antagonist, were prepared from 1,3-dimethyl-4-piperidinone in 11.8% yield (8 steps) and 6.2% yield (12 steps), respectively.",10.1021/jo951403y,1996-01-01,0.5875252427527907
Tetrahedron,"Synthesis of new chiral ferrocenyl P,N-ligands with a benzoxazole ring and their application in Ag-catalyzed asymmetric [3+2] cycloaddition",,10.1016/j.tetlet.2013.05.003,2013-05-10,0.5875249591224642
Journal of Organic Chemistry,Environmentally Benign Route for Scalable Preparation of 1-Imino-3-thioisoindolines−The Key Building Blocks for the Synthesis of Dithio- and Diamino-β-isoindigo Derivatives,"A one-step, gram-scale protocol for the preparation of 1-imino-3-thioisoindolines and a novel one-pot two-step methodology of the synthesis of dithio- or diamino-β-isoindigo derivatives starting from phthalonitriles and sodium hydrosulfide in an aprotic dipolar solvent have been developed. It was demonstrated that the electronic properties of the substituent(s) in the phthalonitrile core play a critical role in β-isoindigo synthesis resulting either in the selective formation of dithio- or diamino-β-isoindigo chromophores. The N -acylated 1-imino-3-thioisoindolines can be used for the direct, easily scalable, and chromatography-free procedure for the preparation of a new class of N, N ′-diacylamino-β-isoindigoid compounds. Properties of the monomeric as well as J-aggregated forms of dithio- and diamino-β-isoindigo were probed by the absorption and fluorescence spectroscopies. It was demonstrated that the tetracyano-diamino-β-isoindigo 3f can form a J-aggregate that absorbs at 793 nm and fluoresces at 824 nm. This aggregate is stable in N, N -dimethylformamide solution; however, it slowly dissociates in tetrahydrofuran or under sonication conditions. Density functional theory (DFT) and time-dependent DFT (TDDFT) calculations were employed to elucidate the electronic structures, spectroscopic properties, and aggregation of new dithio- and diamino-β-isoindigo derivatives.",10.1021/acs.joc.1c00110,2021-03-10,0.5875241140168643
Tetrahedron,"Diastereoselective construction of cis 2,6-disubstituted tetrahydropyran rings via In(OTf)3-catalyzed intramolecular 2,5-oxonium-ene cyclization: synthetic studies towards the total synthesis of zampanolide and dactylolide",,10.1016/s0040-4039(02)01666-0,2002-09-01,0.5875209856703582
Journal of Organic Chemistry,Total Synthesis of the Repeating Unit of <i>Bacteroides fragilis</i> Zwitterionic Polysaccharide A1,"Zwitterionic polysaccharides isolated from commensal bacteria are endowed with unique immunological properties and are emerging as immunotherapeutic agents as well as vaccine carriers. Reported herein is a total synthesis of the repeating unit of Bacteroides fragilis zwitterionic polysaccharide A1 (PS A1). The structurally complex tetrasaccharide unit contains a rare sugar 2-acetamido-4-amino-2,4,6-trideoxy- d -galactose (AAT) and two consecutive 1,2- cis glycosidic linkages. The repeating unit was efficiently assembled by rapid synthesis of d -galactosamine and AAT building blocks from cheap and abundant d -mannose via a one-pot S N 2 displacement of 2,4-bistriflates and installation of all of the glycosidic bonds in a highly stereoselective manner. The total synthesis involves a longest linear sequence of 17 steps with 3.47% overall yield.",10.1021/acs.joc.0c02935,2021-04-12,0.5875193244308137
Organic Letters,Expeditious Total Syntheses of Natural Allenic Products via Aromatic Ring Umpolung,"Concise diastereoselective syntheses of the marine (+/-)-panacene and terrestrial (+/-)-desbromopanacene have been achieved in a few steps based on a concept of ""aromatic ring umpolung"". The synthetic avenue to the (+/-)-panacene involved a novel oxymercuration strategy to produce the correct configuration of the bromoallene moiety.",10.1021/ol801921d,2008-09-19,0.5875137932442381
Tetrahedron,First stereo selective synthesis of 5-O-feruloyl-2-deoxy-d-ribono-γ-lactone,,10.1016/j.tetlet.2016.09.041,2016-09-14,0.5875117797475963
Synthesis,A New Synthetic Approach to Indazole Synthesis,"All articles of this category Stobbe condensation of 3-alkyl- or aryl-4-formylpyrazoles 3a-f with diethyl succinate in the presence of potassium t -butoxide, followed by intramolecular ring closure (Ac 2 O-NaOAc), afforded the corresponding indazole derivatives 5a-f in 65-85% overall yield. These compounds are good starting materials for transformation to biologically active molecules, such as new pyrazole analogs of the left-hand segment of the potent natural antineoplastic agent CC-1065. 4-formyl pyrazoles - indazoles - Stobbe condensation - diethyl succinate - electrocyclic ring closure",10.1055/s-1997-1328,1997-10-01,0.5875070633333253
Organic Letters,"PPA-Mediated C–C Bond Formation: A Synthetic Route to Substituted Indeno[2,1-<i>c</i>]quinolin-6(7<i>H</i>)-ones","A facile and efficient synthesis of substituted indeno[2,1-c]quinolin-6(7H)-ones from a variety of α-acyl N-arylcinnamamides mediated by polyphosphoric acid (PPA) is described, and a mechanism involving the formation of a dicationic superelectrophile and subsequent double intramolecular nucleophilic cyclization reactions is proposed.",10.1021/ol303423f,2013-02-07,0.587500679206156
Synlett,"A New and Facile Method for the Preparation of 3-Substituted Pyrazolo[3,4-c]pyridines","All articles of this category An efficient and facile method for the synthesis of 3-substituted pyrazolo[3,4-c]pyridines is described starting from the readily accessible 3-acetamido-2-methoxy-4-methylpyridine. 3-alkylpyrazolo[3,4-c]pyridines - 3-arylalkylpyrazolo[3,4-c]pyridines - 3-acetamido-4-alkylpyridine ring closure",10.1055/s-1997-3211,1997-05-01,0.587498031857542
Organic Letters,Synthetic Studies Toward Pectenotoxin 2. Part II. Synthesis of the CDE and CDEF Ring Systems,A convergent synthesis of the CDE and CDEF ring systems of pectenotoxin-2 from C and F ring precursors is described.,10.1021/ol801585j,2008-09-03,0.5874903575442745
Tetrahedron,"Synthesis of 18R-hydroxy-epiallo-yohimbines from (−)-3-iso-19,20-dehydro-β-yohimbine: an enantiospecific route to deserpidine and reserpine analogues from secologanin",,10.1016/s0040-4039(00)00913-8,2000-07-01,0.5874881048462504
Tetrahedron,Synthesis of a novel spiro bisphosphinamidite ligand for highly enantioselective hydrogenation,,10.1016/j.tetlet.2004.07.137,2004-08-21,0.5874872285447199
Synthesis,Stereoselective Total Synthesis of (+)-Virol C,"A highly stereoselective synthesis of (+)-Virol C (1) has been achieved starting from octan-1-ol (6) using two different strategies, elimination reactions of epoxyallyl chloride 12 and epoxy chloride 16 to hydroxyenyne 2 and trans-hydroxyalkenyl chloride 4 as key reactions in route a and route b, respectively.",10.1055/s-2003-42465,2003-01-01,0.5874834067151691
Organic Letters,"Direct Entry to 4,10-Didesmethyl (9<i>S</i>)-Dihydroerythronolide A via Catalytic Allene Osmylation","Desmethyl erythronolides have emerged as macrolide targets that may prove effective against resistant bacteria. A five-step sequence to 4,10-didesmethyl (9S)-dihydroerythronolide A (1) from known cyclic bis[allene] 13 is reported. Key structural and mechanistic aspects of the synthesis are discussed along with catalytic allene osmylation. An improved route to 13 is also described.",10.1021/acs.orglett.6b01151,2016-06-07,0.5874799560339261
Tetrahedron,"4,5,6,7-tetradehyro-PG1, a stable and potent inhibitor of blood platelet aggregation",,10.1016/s0040-4039(00)70995-6,1979-01-01,0.5874721801086832
Synlett,Total Synthesis of the Psammaplysins: Evolution of a Dipolar Cycloaddition Approach,"Abstract The psammaplysins are a unique group of bromotyrosine-derived natural products isolated from the Psammaplysilla genus of marine sponges. Aside from the various biological activities they possess, synthetic chemists have been drawn to the family for decades due to the intriguing 5/7-spiroisoxazoline-oxepine core common to all members. Herein, we describe our synthetic approach towards the psammaplysin family in the context of this broader work. Our route centers upon the use of a carefully choreographed alkoxymethylenation/1,3-dipolar cycloaddition to construct the key spiroisoxazoline-oxepine ring system, followed by its functionalization and divergent coupling to access various family members. We also detail the development of the first asymmetric approach to this class of marine natural products. 1 Introduction 2 Initial Synthetic Approach and Challenges Encountered 3 Total Synthesis of Psammaplysins A, M, O and Q and Ceratinamide A 4 Development of an Asymmetric Solution to the Family 5 Conclusions and Outlook",10.1055/a-2526-0553,2025-01-27,0.5874688775834285
Journal of Organic Chemistry,Telescoped Approach to Aryl Hydroxymethylation in the Synthesis of a Key Pharmaceutical Intermediate,"An efficient synthetic approach leading to introduction of the hydroxymethyl group to an aryl moiety via combination of the Bouveault formylation and hydride reduction has been optimized using a rational, mechanistic-based approach. This approach enabled telescoping of the two steps into a single efficient process, readily amenable to scaleup.",10.1021/jo400647t,2013-05-30,0.5874626730202951
Journal of Organic Chemistry,Six-Step Total Synthesis of Azaspirene,"The total synthesis of (±)-azaspirene (1) was achieved in a total of six steps from commercially available materials. Keys to the conciseness of our synthetic approach were the effective γ-lactam formation from linear precursor 36 and successful tandem epoxidations of γ-lactam 34 to afford α,β-epoxy-γ-hydroxy-γ-lactam intermediate 14. While our streamlined synthesis of azaspirene (1) sought inspiration from its biogenetic hypothesis, experimentally observed chemical reactivity of biosynthetically relevant precursors conversely provides insights to the biological origin of this natural product.",10.1021/acs.joc.7b01224,2017-07-12,0.5874594824145231
Organic Letters,Total Synthesis of (±)-Fasicularin via a 2-Amidoacrolein Cycloaddition,"The total synthesis of the cytotoxin fasicularin is described. The key steps include the following: (1) an intermolecular Diels-Alder cycloaddition of a 2-(triflamido)acrolein with the dioxolane ketal of trideca-1,3-dien-7-one to establish the trans-perhydroisoquinoline stereochemistry, (2) a stereoelectronically controlled hydride addition to a N(1)-C(2) iminium ion to introduce the equatorial hexyl substituent, and (3) elaboration of the pyrido ring by an internal aldol reaction.",10.1021/ol016850g,2002-01-09,0.5874480097761119
Journal of Organic Chemistry,One-Pot Synthesis of Cyclic Nitrones and Their Conversion to Pyrrolizidines:  7a-<i>e</i><i>pi</i>-Crotanecine Inhibits α-Mannosidases,"[reaction: see text] A new straightforward and inexpensive one-pot procedure is described for the preparation of enantiopure five-membered cyclic nitrones starting from the corresponding lactols. Its efficiency relies on the condensation of unprotected hydroxylamine with readily available lactols and on the chemoselectivity of the subsequent esterification with methanesulfonyl chloride. The targeted enantiomerically pure pyrroline N-oxides are versatile synthetic intermediates: one of the nitrones so-obtained has been converted into new polyhydroxypyrrolizidines, analogues of the alkaloids rosmarinecine and crotanecine, which were assayed for their inhibitory activities toward 22 commercially available glycosidase enzymes. One of them ((-)-7a-epi-crotanecine) is a potent and selective inhibitor of alpha-mannosidases from jack beans and almonds.",10.1021/jo0523518,2006-01-27,0.5874459735940372
Synlett,A Short and New Synthesis of Optically Pure (+)-Retronecine,"All articles of this category A short synthesis of (+)-retronecine from (R)-3-hydroxy pyrrolidine, utilizing [3 + 2] cycloaddition of cyclic non-stabilized azomethine ylide as the key step is reported.",10.1055/s-1994-22827,1994-01-01,0.5874447085001304
European Journal of Organic Chemistry,An Efficient and Facile Synthesis of Capsaicin‐Like Compounds as Agonists of the TRPV1 Receptor,"Abstract A new versatile synthetic route is described for the preparation of capsaicin‐like molecules which contain an α‐hydroxy ketone functional group mimicking the amide functional group in the capsaicin structure. The key reaction in this synthesis was the formation of α‐(dimethylamino)alkanenitriles as intermediates. These nitriles were successfully prepared from both aliphatic and aromatic aldehydes by reaction with dimethylamine and aqueous sodium cyanide. Treatment of the nitriles with lithium diisopropylamide (LDA) followed by reaction with various aldehydes led to the formation of α‐hydroxy ketone compounds, examples of which include 2‐hydroxy‐1‐(4‐hydroxy‐3‐methoxyphenyl)dodecan‐3‐one,(5 R )‐ and (5 S )‐2‐hydroxy‐1‐(4‐hydroxy‐3‐methoxyphenyl)‐5,9‐dimethyldec‐8‐en‐3‐one, representing novel capsaicin‐like molecules. Formation of (4‐benzyloxy‐3‐methoxyphenyl)acetaldehyde was also described from the Wittig reaction of 4‐benzyloxy‐3‐methoxybenzadehyde with an ylide reagent (methoxymethyl)triphenylphosphonium bromide followed by acid hydrolysis to form the title compound. This aldehyde represents a useful precursor for the synthesis of capsaicin‐like structures.(© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2006)",10.1002/ejoc.200600135,2006-04-21,0.587442179716143
Journal of Organic Chemistry,A Facile Three-Component One-Pot Synthesis of Structurally Constrained Tetrahydrofurans That Are t-RNA Synthetase Inhibitor Analogues,"A one-pot procedure for the efficient synthesis of tRNA inhibitor analogues was developed. Thus, three-component 1,3-dipolar cycloaddition reactions of carbonyl ylides derived from diazoindan-1,3-dione and aldehydes with other dipolarophiles in 1,1,2,2-tetrachloroethane in 80 degrees C gave ring-fused tetrahydrofurans having three stereocenters in good yield.",10.1021/jo0497508,2004-06-11,0.5874420796786275
Tetrahedron,A synthetic approach to the phorboxazoles – A strategy for the synthesis of the C1–C19 polyketide fragment,,10.1016/j.tetlet.2017.12.007,2017-12-06,0.5874369977542586
Synlett,"Efficient Synthesis of 5-Alkoxy-(3R)-hydroxy-2,3-dihydrospiro[indene-1,4′-piperidines]: A Novel Scaffold for Renin Inhibitors","We report herein, an efficient synthetic method for the preparation of a 5-alkoxy-(3R)-hydroxy-2,3-dihydrospiro[indene-1,4′-piperidines] scaffold using a regioselective intermolecular ­reaction and a stereoselective reduction as key steps. Compound 2, based on this scaffold, showed moderate in vitro binding affinity for purified human renin.",10.1055/s-0029-1217818,2009-08-17,0.5874360561455667
Journal of Organic Chemistry,Stereodivergent Resolution of Oxabicyclic Ketones: Preparation of Key Intermediates for Platensimycin and Other Natural Products,"An improved methodology for the preparation of enantiopure oxabicyclo[3.2.1]octadienes via a stereodivergent resolution is reported. High catalyst control proximal to the oxabridged stereocenter produces readily separable diastereomers in high yield (>92%) and with excellent optical purity (>95% ee). This resolution strategy is amenable to large-scale preparations, and the utility of the resolution was further demonstrated in the asymmetric preparation of a key intermediate used in the synthesis of the antibiotic (-)-platensimycin.",10.1021/jo4017502,2013-09-18,0.5874319610716345
Organic Letters,"<i>N</i>,<i>N</i>-Acetals as <i>N</i>-Acyliminium Ion Precursors: Synthesis and Absolute Stereochemistry of Epiquinamide","A stereoselective synthesis of (+)-epiquinamide is presented in combination with determination of the absolute configuration of the natural product. Key steps in the sequence involved chemoenzymatic formation of an enantiomerically pure cyanohydrin, reductive cyclization to the corresponding cyclic N,N-acetal, and subsequent conversion into a suitable N-acyliminium ion precursor to enable construction of the second ring.",10.1021/ol801490m,2008-08-15,0.5874308859642464
Tetrahedron,One-step synthesis of a new heterocyclophane family,,10.1016/j.tetlet.2008.12.023,2008-12-12,0.5874254769098717
Angewandte Chemie International Edition,"A Bioinspired Synthesis of (±)‐Rubrobramide, (±)‐Flavipucine, and (±)‐Isoflavipucine","A biomimetic synthesis of naturally occurring lactams rubrobramide, flavipucine, and isoflavipucine is described. The key step is a regioselective Darzens reaction between isobutyl glyoxal and an α-bromo-β-ketoamide. The construction of the core tricyclic ring system of rubrobramide was achieved by a cascade reaction in a single step from an α,β-epoxy-γ-lactam. Furthermore, the absolute configuration of naturally occurring (+)-rubrobramide was determined by vibrational circular dichroism. (±)-Flavipucine and (±)-isoflavipucine were synthesized from an epoxyimide, which was prepared by reaction of isobutyl glyoxal with a protected α-bromo-β-ketoamide. Deprotection of the epoxyimide and formation of the pyridone ring gave (±)-flavipucine, which was converted into (±)-isoflavipucine by thermal isomerization.",10.1002/anie.201602910,2016-07-04,0.587411388707005
Tetrahedron,"A short, efficient total synthesis of (±) acivicin and (±) bromo-acivicin",,10.1016/s0040-4039(00)99918-0,1984-01-01,0.5874073704759103
Tetrahedron,Stereoselective synthesis of cis-substituted azetidinones from penicillin: A formal total synthesis of loracarbef,,10.1016/s0040-4039(00)93376-8,1993-05-01,0.5874045870683174
Organic Letters,Syntheses of Millingtonine and Incargranine A Following a Unified Cross-Dimerization-Aromatization Strategy,"Millingtonine and incargranine A are alkaloids featuring a tricyclic scaffold consisting of pyrrolidine, tetrahydrofuran, and cyclohexanone. While literature reports two synthons for C 6 C 2 units for the installation of enone and aromatic core units in the alkaloids involving multiple steps and expensive reagents, the present strategy depicts a true biosynthetic route using p -quinol as a single C 6 C 2 synthon under transition metal-free synthetic routes in four steps. The reaction proceeds via cross-coupling of in situ generated N -aryl enamine with p -quinol, marking a significant advancement in alkaloid synthesis.",10.1021/acs.orglett.5c04115,2025-10-31,0.5874018664271713
Angewandte Chemie International Edition,Tribenzotriquinacene: A Versatile Synthesis and <i>C</i><sub>3</sub>‐Chiral Platforms,Fusing rings: A new synthesis of the bowl-shaped hydrocarbon tribenzotriquinacene is presented (see scheme). The synthesis allows easy access to ortho-functionalized and C3-chiral derivatives that are attractive for supramolecular chemistry and asymmetric catalysis.,10.1002/anie.201207220,2012-11-09,0.5874007525744543
European Journal of Organic Chemistry,New Methodology for the Stereoselective Synthesis of α‐Furfurylamines from Sugars: Application to the Synthesis of Furyl Amino Acids and 3‐Furylisoserines,"Abstract The synthesis of two new furyl amino acids as rigid isosteres of the dipeptides ( D )‐H‐Ser‐( D , L )‐Thr‐OH and ( L )‐H‐Ser‐( D , L )‐Thr‐OH is presented. The developed synthetic methodology starts from D ‐xylose and D ‐arabinose and makes use of trihydroxypropylfurans as intermediates. The key step of the strategy is the introduction of an amino function at the α‐position of the adequate trihydroxypropylfuran derivative. This methodology was also applied to the synthesis of two new (2 R ,3 R )‐3‐furylisoserines as analogues of the C‐13 Taxol/Taxotere side chain.",10.1002/ejoc.201000183,2010-04-29,0.5874000973425502
Angewandte Chemie International Edition,Stereocontrolled Total Synthesis of Bengazole A: A Marine Bisoxazole Natural Product Displaying Potent Antifungal Properties,"Candidate for Candida: A high-yielding and versatile synthesis of bengazole A has been developed; the first to provide access to a single stereoisomer of the natural product. Key steps include the construction of the 2,4-disubstituted oxazole under mild conditions and a diastereoselective 1,3-dipolar cycloaddition.",10.1002/anie.200602050,2006-09-20,0.5873986982791679
Tetrahedron,Structure of a new topoisomerase II inhibitor BE 10988,,10.1016/0040-4039(91)85087-l,1991-06-01,0.5873985839907512
Journal of Organic Chemistry,"Total Synthesis of 7′-Desmethylkealiiquinone, 4′-Desmethoxykealiiquinone, and 2-Deoxykealiiquinone","Synthetic approaches to the imidazonaphthoquinone core of kealiiquinone and related Leucetta-derived alkaloids are described. The polysubstituted benzimidazole framework can be constructed through intramolecular Diels-Alder reactions of propiolate-derived enynes followed by oxidation. Adjustment of the oxidation state of the thus formed lactone allows introduction of the 2,3-dihydroxybenzoquinone moiety through a presumed benzoin-like condensation between a phthaldehyde derivative and a masked glyoxal equivalent catalyzed by a cyanide ion. Oxidation of the C2-position can be accomplished through application of an operationally simple treatment of an imidazolium salt with bleach, thus producing the corresponding 2-imidazolone. Debenzylation of a late stage intermediate en route to kealiiquinone was compromised by concomitant O-demethylation upon treatment with triflic acid resulting in the formation of non-natural 7'-desmethylkealiiquinone. Other endgame strategies were evaluated; however, these efforts did not lead to completion of a synthesis of kealiiquinone but did provide access to other closely related analogues.",10.1021/jo4027337,2014-02-17,0.5873970551228612
Journal of Organic Chemistry,A Protecting Group Free Synthesis of (±)-Neostenine via the [5 + 2] Photocycloaddition of Maleimides,"A concise, linear synthesis of the Stemona alkaloid (+/-)-neostenine is reported. Key features include an organocopper-mediated bislactone C2-desymmetrization for the stereoselective construction of the cyclohexane-lactone C,D-rings. The assembly of the fused pyrrolo[1,2-a]azepine core was achieved by application of a [5 + 2] maleimide photocycloaddition. A custom FEP flow reactor was used to successfully overcome the scale limitations imposed by a classical immersion well batch reactor. The synthesis was completed in 14 steps from furan, in 9.5% overall yield, without the use of any protecting groups.",10.1021/jo801108h,2008-07-26,0.5873912565324095
Journal of Organic Chemistry,Synthesis of New Chromogenic Calix[4]arenes Bridged at the Upper Rim through Bisazobiphenyl Linkages,"Synthesis of new chromogenic calix[4]arenes through the coupling of diazotized 4,4‘-diaminobiphenyls and calix[4]arenes at the upper rim is described. Analysis of the synthesized bisazobiphenyl-bridged calixarenes by NMR and CPK models suggest that the bisazobiphenyl linkage is on the transannular phenyl groups of the calixarene moiety in the 1,3-alternate conformation.",10.1021/jo950808f,1996-01-01,0.5873832772288671
Tetrahedron,"A practical synthesis of Cbz protected (1R,2R) and (1S,2S) 2-hydroxy-cyclobutylamines",,10.1016/j.tetlet.2024.155391,2024-11-23,0.587379724052615
Synlett,An Efficient Three-Step Synthesis of L-(-)-Oleandrose from (<i>S</i>)-(-)-Methyl Lactate,"All articles of this category L-(-)-Oleandrose ( 1 ; 2,6-dideoxy-3- O -methyl- arabino -hexose) was prepared in only three steps from ( S )-(-)-methyl lactate and (3-butenylsulphonyl)benzene, without the use of protecting groups. A stereocontrolled reduction and a thermodynamically controlled exchange reaction afforded the required arabino configuration.",10.1055/s-1990-21247,1990-01-01,0.5873747934525019
Tetrahedron,"The first total synthesis of veiutamine, a new type of pyrroloiminoquinone marine alkaloid",,10.1016/s0040-4039(99)00034-9,1999-02-01,0.5873697102724388
Angewandte Chemie International Edition,Iridium‐Catalyzed Enantioselective Indole Cyclization: Application to the Total Synthesis and Absolute Stereochemical Assignment of (−)‐Aspidophylline A,"The first enantioselective total synthesis of (-)-aspidophylline A, including assignment of its absolute configuration has been accomplished. A key element of the synthesis is a highly enantioselective indole allylic alkylation/iminium cyclization cascade which was developed by employing a combination of Lewis acid activation and an iridium/ligand catalyst. This strategy relies on the direct use of 2,3-disubstituted indoles with secondary allylic alcohols appended at C2 and heteronucleophiles appended at C3, indoles which are easily prepared from simple starting materials under C-H activation conditions.",10.1002/anie.201511549,2016-02-17,0.5873694512569505
Synlett,A Facile One-Pot Synthesis of Isocoumestans<i>via</i>a Novel Extension of the Castro Cyclization of<i>o</i>-Iodophenols and Ethyl Propiolate,"All articles of this category Treatment of o -iodophenols with ethyl propiolate in the presence of copper(I) tert -butoxide affords isocoumestans (6 H -benzofuro[2,3- c ][1]benzopyran-6-ones) in a one-pot synthesis. The reaction is considered to be an extended Castro cyclization where an intermediate cupriated benzofuran couples with additional o -iodophenol, and the product lactonizes to isocoumestan.",10.1055/s-1991-34778,1991-01-01,0.5873670592025779
Organic Letters,Synthesis of (±)-Bisavenanthramide B-6 by an Anionic Anhydride Mannich Reaction,Bisavenanthramide B-6 (2) is a highly substituted γ-lactam derived from oat leaves. Development of a new base-promoted anhydride Mannich reaction with N-sulfonylated imines that forms the core structure of 2 in a single step is presented. Further elaboration allows for a facile one-pot double Buchwald N-arylation to install the final rings onto the densely substituted γ-lactam core. This route provides the natural product in a longest linear sequence of nine steps.,10.1021/acs.orglett.6b00413,2016-03-29,0.5873661668341129
Organic Letters,Approach to the Synthesis of Dolabelides A and B:  Fragment Synthesis by Tandem Silylformylation−Crotylsilylation,"[structure: see text] A synthesis of the C(15)-C(30) fragment of Dolabelides A and B has been achieved. The recently developed asymmetric silane alcoholysis and tandem silylformylation-crotylsilylation reactions were used as the key steps to establish the C(23)-C(27) 1,5-syn-diol. In addition, the flexibility of this methodology has been demonstrated with an efficient synthesis of the C(24)-C(25) trisubstituted olefin.",10.1021/ol035431b,2003-08-20,0.5873602126647062
Tetrahedron,A new dynamic resolution strategy for asymmetric synthesis,,10.1016/0040-4039(95)02379-8,1996-02-01,0.5873594692457665
Synlett,Diastereoselective Construction of New 5a-Substituted Carbaallose by exo-β-Selective Conjugate Addition to endo-exo Cross-Conjugated Cyclohexadienone as Key Reaction,"Practical synthesis of a new chiral endo-exo cross-conjugated cyclohexadienone was achieved, and its synthetic utility was illustrated by highly exo-β-selective conjugate addition with various nucleophiles. Further diastereoselective transformation of the adduct to an unprecedented 5a-substituted carbaallose is also described.",10.1055/s-0030-1258028,2010-08-09,0.5873547158564865
Synthesis,"Methods of Synthesis of Remdesivir, Favipiravir, Hydroxychloroquine, and Chloroquine: Four Small Molecules Repurposed for Clinical Trials during the Covid-19 Pandemic","Abstract The novel coronavirus (COVID-19) disease has rapidly evolved into a sweeping pandemic despite public health measures. Screening and development of new vaccines and antivirals are expensive and time consuming. However, the repositioning of available drugs is an essential and universal strategy in the development of new drugs and therefore should receive priority attention as well as international government and agency support. Significant drugs such as chloroquine, hydroxychloroquine, favipiravir and remdesivir, are currently undergoing clinical studies to test their efficacy and safety. Some promising results have been achieved thus far in the treatment of COVID-19. In this article we summarize and discuss the most common synthetic strategies to apply in the preparation of these drug molecules. It is hoped that this compendium will provide an accessible useful guide and reference source for scientists, researchers and academia in their battle against COVD-19. 1 Introduction 2 Synthesis of Chloroquine (CQ) and Hydroxychloroquine (HCQ) 2.1 Synthesis of 4,7-Dichloroquinoline 1 2.2 Synthesis of 2-Amino-5-(diethylamino)pentane (Novoldiamine) 2 2.3 Synthesis of 5-(N-Ethyl-N-2-hydroxyethylamino)-2-pentylamine 4 2.4 Developed Methods for Synthesis of Chloroquine and Hydroxychloroquine 2.5 Synthesis of (R)-Chloroquine, (S)-Chloroquine, (R)-Hydroxychloroquine and (S)-Hydroxychloroquine 3 Synthesis of Favipiravir (Avigan) 4 Synthesis of Remdesivir 5 Conclusion",10.1055/s-0040-1707386,2020-09-11,0.5873543814610546
Tetrahedron,Vicinal polyepoxides in biomimetic synthesis. Total synthesis of (±)-citreoviral and related substituted tetrahydrofurans,,10.1016/0040-4039(92)88098-p,1992-07-01,0.5873539247176754
Journal of the American Chemical Society,Anodic Cyclization Reactions:  The Total Synthesis of Alliacol A,An anodic cyclization-Friedel Crafts alkylation strategy has been used to rapidly assemble the core ring system of alliacol A and to complete a formal total synthesis of the natural product. The anodic cyclization reaction was used to effect the coupling of a nucleophilic furan ring to the normally nucleophilic carbon of a silyl enol ether. The substrate for this initial cyclization reaction contained all of the carbons needed for completing the total synthesis. The electrolysis proceeded in high yield and could be accomplished with the use of a 6 V lantern battery.,10.1021/ja029064v,2002-12-05,0.5873479424814005
Angewandte Chemie International Edition,Enantioselective Total Synthesis and Structural Revision of Dysiherbol A,"A 12-step total synthesis of the natural product dysiherbol A, a strongly anti-inflammatory and anti-tumor avarane meroterpene isolated from the marine sponge Dysidea sp., was elaborated. As key steps, the synthesis features an enantioselective Cu-catalyzed 1,4-addition/enolate-trapping opening move, an Au-catalyzed double cyclization to build up the tetracyclic core-carbon skeleton, and a late installation of the C5-bridgehead methyl group via proton-induced cyclopropane opening associated with spontaneous cyclic ether formation. The obtained pentacyclic compound (corresponding to an anhydride of the originally suggested structure for dysiherbol A) showed identical spectroscopic data as the natural product, but an opposite molecular rotation. CD-spectroscopic measurements finally confirmed that both the constitution and the absolute configuration of the originally proposed structure of (+)-dysiherbol A need to be revised.",10.1002/anie.202105733,2021-05-12,0.5873457070120987
Journal of Organic Chemistry,A Synthesis of Oseltamivir (Tamiflu) Starting from <scp>d</scp>-Mannitol,"A synthesis of oseltamivir (Tamiflu) was achieved starting from D-mannitol. A unique feature of the synthetic route is that an acyclic precursor was constructed, which was then cyclized in an intramolecular aldol reaction to form the Tamiflu skeleton. Throughout the synthesis, well-established, highly efficient reactions were employed, and no protection/deprotection sequence was needed.",10.1021/jo101517g,2010-09-24,0.5873292109563331
Organic Letters,Expedient Synthesis of Chiral Oxazolidinone Scaffolds via Rhodium-Catalyzed Asymmetric Ring-Opening with Sodium Cyanate,A method for synthesizing chiral oxazolidinone scaffolds from readily available oxabicyclic alkenes is described. The reaction utilizes a domino sequence of Rh(I)-catalyzed asymmetric ring-opening (ARO) with sodium cyanate as a novel nucleophile followed by intramolecular cyclization to generate oxazolidinone products in excellent enantioselectivities (trans stereochemistry).,10.1021/ol4000668,2013-02-08,0.5873225146772699
Synthesis,An Enantiospecific Approach to Triazolylalanine Derivatives,An efficient and practical route to an enantiomerically pure aziridinylmethyl azide is described that can be transformed to the corresponding triazole by a copper-catalysed [3+2] alkyne cycloaddition reaction. The transformation of these intermediates into triazolylalanine-type derivatives by aziridine ring-opening reactions is also described.,10.1055/s-0028-1083270,2008-12-12,0.5873214808562284
Angewandte Chemie International Edition,From Glycals to Glycopeptides: A Convergent and Stereoselective Total Synthesis of a High Mannose N-Linked Glycopeptide,A concise and totally synthetic route involving the merger of a fully deprotected glycosylamine and a minimally protected aspartic acid containing peptide has enabled the homogeneous N-linked glycopeptide 1 to be synthesized. The other key conversions in the synthesis are the progression from glycal to free oligosaccharide hemiacetal and subsequent amination with high efficiency.,10.1002/1521-3773(20001016)39:20<3652::aid-anie3652>3.0.co;2-b,2000-10-16,0.5873147692614313
Tetrahedron,Enantioselective synthesis of an advanced intermediate to quassinoids,,10.1016/s0040-4039(00)73071-1,1994-05-01,0.5873081337791652
Organic Letters,Synthesis of the Potent Antimalarials Calothrixin A and B,A concise synthesis of calothrixins A (1) and B (2) that confirms their assigned structures and affords straightforward synthetic access to them is reported.,10.1021/ol006649q,2000-10-21,0.5873079085282088
Organic Letters,"Concise and Highly Stereocontrolled Synthesis of 1-Deoxygalactonojirimycin and Its Congeners Using Dioxanylpiperidene, a Promising Chiral Building Block","[reaction: see text] A concise and stereoselective synthesis of the chiral building block, dioxanylpiperidene 4 as a precursor for deoxyazasugars, starting from the Garner aldehyde 5 using catalytic ring-closing metathesis (RCM) for the construction of the piperidine ring is described. The asymmetric synthesis of 1-deoxygalactonojirimycin and its congeners 1-3 was carried out via the use of 4 in a highly stereocontrolled mode.",10.1021/ol034886y,2003-06-19,0.5873068411017318
Organic Letters,Asymmetric Synthesis of the Tricyclic Core of NGF-Inducing Cyathane Diterpenes via a Transition-Metal-Catalyzed [5 + 2] Cycloaddition,"[reaction: see text] A concise asymmetric synthesis of the tricyclic core of cyathane diterpenes is described, based on a novel transition-metal-catalyzed intramolecular [5 + 2] cycloaddition of ynone-vinylcyclopropane 10 (assembled from commercially available (S)-(-)-limonene), which proceeds in 90% yield with >95% selectivity. This strategy provides efficient access (14 steps and 13% overall yield) to potential analogues as well as precursors of nerve growth factor (NGF)-inducing diterpenes.",10.1021/ol0160699,2001-06-01,0.5873054893876015
Organic Letters,Synthesis of Chiral .GAMMA.-Lactams via in Situ Elimination/Iridium-Catalyzed Asymmetric Hydrogenation of Racemic .GAMMA.-Hydroxy .GAMMA.-Lactams,,,2017-01-01,0.5873053994603832
Tetrahedron,Asymmetric glycolate alkylation approach towards total synthesis of 8-O.6′ and 8-O.4′-neolignans,,10.1016/j.tetlet.2016.11.087,2016-11-21,0.5873041120216955
Chemical Science,"Halogenation-induced C–N bond activation enables the synthesis of 1,2- <i>cis C</i> -aryl furanosides <i>via</i> deaminative cyclization","A streamlined approach for the selective synthesis of 1,2- cis C -aryl furanosides from unprotected aldoses in two steps.",10.1039/d4sc07410f,2024-12-02,0.5873012994859793
Angewandte Chemie International Edition,Total Synthesis of Fostriecin (CI-920),"The most selective protein phosphatase inhibitor identified to date, fostriecin was synthesized in a highly convergent manner by a chiral building block approach (see picture). Three of the four stereocenters were introduced by using catalytic methods, including novel and practical applications of asymmetric hetero-Diels–Alder (HDA) and hydrolytic kinetic resolution reactions.",10.1002/1521-3773(20011001)40:19<3667::aid-anie3667>3.0.co;2-6,2001-10-01,0.5872977846805622
Organic Letters,Total Synthesis and Bioactivity of Resolvin E2,"Resolvin E2 is a potent anti-inflammatory compound, derived from eicosapentaenoic acid. The efficient total synthesis of resolvin E2 by taking advantage of its intrinsic pseudoenantiomeric substructures is reported. The synthetic resolvin E2 proved to be biologically active in blocking neutrophil infiltration and reducing proinflammatory cytokines in the acute peritonitis model.",10.1021/ol901350g,2009-08-13,0.5872786921725949
Journal of Organic Chemistry,A Concise Total Synthesis of Dactylol via Ring Closing Metathesis,"A straightforward total synthesis of the cyclooctenoid sesquiterpene dactylol (1) and of 3a-epi-dactylol (13) has been achieved in six synthetic operations. The unusual rearranged bicyclo[6.3.0]undecane isoprenoid skeleton of these target molecules has been formed via an initial three-component coupling triggered by 1,4-addition of a methylcopper reagent (MeLi, CuI, Bu(3)P) to cyclopentenone, followed by trapping of the enolate formed with 2,2-dimethyl-4-pentenal as the electrophile. The aldol 8 thus obtained was elaborated into the trans-disubstituted cyclopentanone derivative 10 which reacted with a methallylcerium reagent to afford a mixture of the tertiary alcohols 11a and 12a. Separation and O-silylation of these diastereoisomers, ring-closing metathesis (RCM) of the resulting dienes 11b and 12b to form the cyclooctene ring using Schrocks molybdenum carbene 5 as a precatalyst, and a final deprotection afforded the title compound and its epimer in excellent yields. This approach clearly surpasses previous ones in terms of efficiency, flexibility, accessibility of the substrates, number of steps, atom economy, and overall yield.",10.1021/jo961600c,1996-01-01,0.5872770397696151
Organic Letters,Rapid Access to the Tricyclic Spirotetronic Core of Abyssomicins,"[reaction: see text] Abyssomicins, a novel class of polyketide antibiotics, are characterized by an unprecedented spirotetronic tricyclic subunit in their structure. In this letter, a short synthesis of a suitably functionalized tricyclic precursor of abyssomicins is reported. Key steps of the synthesis are (i) the highly stereoselective Al(III)-tethered Diels-Alder reaction and (ii) the tandem Dieckmann cyclization/TBS trapping of the C9 hydroxyl group followed by a regioselective intramolecular epoxide opening for the assembly of the target tricyclic structure.",10.1021/ol051872e,2005-08-31,0.587264738046831
Journal of Organic Chemistry,Total Synthesis of (±)-Spiniferin-1 via a Polyfluoroalkanosulfonyl Fluoride Induced Homoallylic Carbocation Rearrangement Reaction,"A facile total synthesis of marine natural product (±)-spiniferin-1 has been accomplished in eight steps with 28.9% overall yield, involving a rearrangement reaction initiated by polyfluoroalkanosulfonyl fluoride to construct the 1,6-methano[10]annulene core of the natural product as a key step.",10.1021/jo102351k,2011-01-20,0.5872645624065441
Angewandte Chemie International Edition,Total Synthesis of Aplydactone by a Conformationally Controlled C−H Functionalization,"A concise, protecting-group-free total synthesis of the unusual brominated sesquiterpene aplydactone is described. Our synthesis features a [2+2] photocycloaddition, a Wolff ring contraction, an unusual remote C-H functionalization to establish the highly strained tetracyclic core, and a hydrogen-atom transfer (HAT) reaction to access the bromine-containing stereocenter. A finely tuned conformation of the α-diazoketone precursor is the key for the success of the late-stage transannular C-H insertion to deliver a bridged six-membered ring and a quaternary stereocenter (C6) between two quaternary carbon atoms (C1 and C7).",10.1002/anie.201703803,2017-05-03,0.5872603759112384
Green Chemistry,"A scalable carboxylation route to furan-2,5-dicarboxylic acid","2-Furoic acid is converted to furan-2,5-dicarboxylic acid in high yield on a mole scale using carbonate-promoted C–H carboxylation.",10.1039/c7gc01059a,2017-01-01,0.5872602947011875
European Journal of Organic Chemistry,Exploitation of Furanoid 5‐Azido‐3‐<i>C</i>‐Branched‐Chain Sugars Towards Highly Functionalized Nitrogen‐Containing Carbohydrate Derivatives,"Abstract The ability of easily accessed 1,2‐ O ‐protected 5‐azido‐3‐ C ‐(ethoxycarbonyl)methylenefuranoses to serve as precursors for the generation of imino sugar derivatives containing an α,β‐unsaturated lactone or ketone functionality has been investigated. A key aspect was the propensity of the corresponding deprotected δ‐amino α,β‐unsaturated esters to undergo 5‐aminofuranose/iminopyranose isomerization. Acid hydrolysis of the δ‐amino ( Z )‐α,β‐unsaturated ester followed by treatment with base led to a butenolide‐containing N ‐ethylformamide arising from a rearrangement of the imino‐sugar‐fused butenolide intermediate induced by the conjugated system. When carrying out the ring expansion step under neutral conditions, a 2‐keto imino sugar was obtained that was readily converted into a 1,2‐dihydropyridin‐3‐one by acetylation. Furthermore, reduction of the δ‐azido ( E )‐α,β‐unsaturated ester to the amine was followed by spontaneous intramolecular cyclization, providing the related furanose‐fused unsaturated δ‐lactam.",10.1002/ejoc.201001119,2010-12-17,0.5872531431923562
Organic Letters,Total Synthesis of Quinolizidine Alkaloid (−)-217A. Application of Iminoacetonitrile Cycloadditions in Organic Synthesis,[reaction: see text] An intramolecular iminoacetonitrile [4 + 2] cycloaddition functions as the key step in an efficient total synthesis of the quinolizidine alkaloid (-)-217A.,10.1021/ol051185n,2005-06-15,0.5872526541504169
Angewandte Chemie International Edition,Total Synthesis and Confirmation of the Revised Structures of Azaspiracid‐2 and Azaspiracid‐3,"The 39 steps: The recently proposed revised structures of azaspiracid-2 and -3 (see picture), the two most potent members of the azaspiracid family, have been confirmed through the total syntheses of the two compounds. These 39-step syntheses represent a major improvement over the first-generation synthesis of azaspiracid-1 (50 steps).",10.1002/anie.200600295,2006-03-20,0.5872505420180527
Organic Letters,"Asymmetric Synthesis of 2-Aryl-2,3-dihydro-4-quinolones via Bifunctional Thiourea-Mediated Intramolecular Cyclization","A novel asymmetric preparation of optically enriched 2-aryl-2,3-dihydroquinolin-4(1H)-ones has been developed. By installing a sulfonyl group on the nitrogen of the anilines and an ester function on the unsaturated ketones, an intramolecular organocatalytic cyclization took place readily in a stereoselective manner, resulting in the formation of dihydroquinolones with high enantioselectivity.",10.1021/ol102519z,2010-11-03,0.5872447812233791
Synlett,Mandelic Acid as Synthetic Equivalent of Benzoyl Carbanion. Synthesis of Nitrobenzophenones,"Nitrobenzophenones are prepared from a mandelic acid dioxolanone. The sequence starts with the aromatic nucleophilic substitution of the enolate of the dioxolanone onto p-fluoronitrobenzenes, followed by hydrolysis of the acetal moiety and oxidative decarboxylation of the resulting α-hydroxyacids. The whole sequence involves the use of mandelic acid as synthetic equivalent of the benzoyl carbanion.",10.1055/s-2003-42123,2003-01-01,0.5872344525375048
Angewandte Chemie International Edition,Facile [7C+1C] Annulation as an Efficient Route to Tricyclic Indolizidine Alkaloids,"A handle on annulation: The two alkenoyl moieties of the cyclic dithiolane are parallel to each other and enables the [7C+1C] annulation with ethyl isocyanoacetate to occur. As a result, tricyclic indolizidine alkaloids are constructed by a two-step, base-catalyzed [7C+1C] annulation/intramolecular cyclization with subsequent reduction/cyclization.",10.1002/anie.201303604,2013-07-02,0.58723231232348
Tetrahedron,A new synthetic approach to cyclosat1vene and similar tetracyclic sesquiterpenes and synthesis of a tetracyclic monoterpene,,10.1016/s0040-4039(00)78936-2,1976-12-01,0.5872295527532791
Synlett,An Efficient Strategy for the Synthesis of New Chiral and Prochiral Trisphosphines,"All articles of this category The synthesis of a series of chiral and prochiral tris(diphenylphosphines) starting from ( R,R )-tartaric acid or erythritol, respectively, is described. The new compounds based on a rigid 1,3-dioxolane ring may be useful as tridentate ligands for the complexation of several metals in different bonding modes. Stereoselective Synthesis - Acetals - Trisphosphines - Tripodal Ligands",10.1055/s-1996-5374,1996-03-01,0.5872205687103672
Synlett,"Synthesis of Thieno[2,3-d]imidazoles by Copper-Catalyzed Amidine Cyclization","A new synthetic approach to thieno[2,3- d ]imidazoles is presented on the basis of the N ′-(3-halothiophen-2-yl)amidine cyclization under copper-catalyzed cross-coupling. Using commercially available starting materials such as 2-aminothiophenes or their Boc-protected derivatives and copper catalysts, this method offers a convenient route to a wide range of thieno[2,3- d ]imidazole derivatives, especially the 5-alkyl-subtituted thieno[2,3- d ]imidazoles.",10.1055/s-0033-1340959,2014-03-14,0.5872141548244287
Synthesis,Synthesis of Tercyclohexanones,"All articles of this category A synthetic route to tercyclohexanones is described in which alkylation of 4-cyclohexylcyclohexanone with the dianion of 4,4-(ethylenedioxy)cyclohexanecarboxylic acid gives 1-carboxy-1′-hydroxyl-1,1′:4′,1″-tercyclohexan-4-one ethylene ketal. Decarboxylative dehydration of the latter followed by hydrolysis of the ketal gives 4-(4′-cyclohexylcyclohexylidene)cyclohexanone. Hydrogenation of this compound gives cis - and trans -1,1′:4′,1″-tecyclohexan-4-one, the latter of which is correlated with authentic trans -1,1′:4′,1″-tercyclohexane.",10.1055/s-1990-27091,1990-01-01,0.5872080054108441
Journal of the American Chemical Society,"Synthesis of a Novel, Highly Symmetric Bis-Oxa-Bridged Compound","A highly oxygenated, novel pentacyclic bis-oxa-bridged compound 8 was synthesized with remarkable efficiency starting from readily available tetrachloro-5,5-dimethoxyclopentadiene and 1,4-cyclohexadiene in three steps. The ruthenium-catalyzed oxidation of 2:1 bis-adduct 1 followed by a one-pot transformation of the resulting bis-alpha-diketone 3 furnished (after esterification) the title compound in an overall yield of 29.1%. The versatility of this simple method was further demonstrated with other norbornyl alpha-diketones to obtain the corresponding strained oxa-bridged derivatives.",10.1021/ja017371f,2002-02-21,0.587206650368374
Tetrahedron,An enantioselective synthesis of (+)-hygroline and (+)-pseudohygroline via Keck allylation and CBS reduction,,10.1016/j.tetlet.2015.06.012,2015-06-12,0.587205121765537
Synthesis,"Synthesis of α-Isocyano-α-alkyl(aryl)acetamides and their Use in the Multicomponent Synthesis of 5-Aminooxazole, Pyrrolo[3,4-<i>b</i>]pyridin-5-one and 4,5,6,7-Tetrahydrofuro[2,3-<i>c</i>]pyridine","alpha -Isocyano-beta -phenylpropionamide is synthesized from the corresponding amino acid in excellent yield. The unique reactivity of this bifunctional compd. is exploited for the development of novel multicomponent synthesis of 5-aminooxazole, pyrrolo[3,4-b]pyridin-5-one, and 4,5,6,7-tetrahydrofuro[2,3-c]pyridine. [on SciFinder (R)]",10.1055/s-2004-831225,2004-09-16,0.587202158208261
Angewandte Chemie International Edition,Biomimetic Synthesis of Meroterpenoids by Dearomatization‐Driven Polycyclization,"A biomimetic route to farnesyl pyrophosphate and dimethyl orsellinic acid (DMOA)-derived meroterpenoid scaffolds has yet to be reported despite great interest from the chemistry and biomedical research communities. A concise synthetic route with the potential to access DMOA-derived meroterpenoids is highly desirable to create a library of related compounds. Herein, we report novel dearomatization methodology followed by polyene cyclization to access DMOA-derived meroterpenoid frameworks in six steps from commercially available starting materials. Furthermore, several farnesyl alkene substrates were used to generate structurally novel, DMOA-derived meroterpenoid derivatives. DFT calculations combined with experimentation provided a rationale for the observed thermodynamic distribution of polycyclization products.",10.1002/anie.201910710,2019-09-13,0.5872012461917492
Tetrahedron,"Synthesis of A575C, a combined angiotensin converting enzyme inhibitor-beta adrenoceptor antagonist",,10.1016/s0040-4039(00)80213-0,1988-01-01,0.5871974797596597
Journal of Organic Chemistry,"An Efficient Highly Regioselective Synthesis of 2,3,4-Trisubstituted Pyrroles by Cycloaddition of Polarized Ketene <i>S</i>,<i>S-</i> and <i>N</i>,<i>S-</i>Acetals with Activated Methylene Isocyanides","An efficient route for regioselective synthesis of 2,3,4- substituted pyrroles allowing precise control over the introduction of a number of substituents and functionalities (tosyl, carbalkoxy, aryl, cyano, nitro, acetyl, benzoyl, cyclic amines, etc.) at the three positions of the pyrrole ring has been developed via 1,3-dipolar cycloaddition of readily accessible polarized ketene S,S- and N,S-acetals with carbanions derived from activated methylene isocyanides.",10.1021/jo062139j,2007-01-25,0.5871794719649925
Synlett,"Branched-Chain Sugars: Improved Synthetic Approach to 3-<i>O</i>-Substituted Derivatives of 5,6-Dideoxy-5-<i>C</i>-hydroxymethyl-1,2-<i>O</i>-isopropylidene-α-D-<i>xylo</i>-hept-5-enofuranurono-7,5'-lactone and (1<i>R</i>, 2<i>R</i>, 4<i>R</i>)-4-(3-Furyl)-1,2-isopropylidenedioxytetrahydrofuran","All articles of this category An improved synthetic approach to the title branched-chain sugars 4 and 5 , starting from ""diacetone glucose"" 1 (1,2:5,6-di- O -isopropylidene-α-D-glucofuranose) is described.",10.1055/s-1990-21024,1990-01-01,0.5871785494573547
Tetrahedron,Studies towards the total synthesis of taxoids synthesis of an A-ring building unit,,10.1016/s0040-4039(00)77510-1,1993-02-01,0.5871784965627561
Angewandte Chemie International Edition,Total Synthesis of Talatisamine,"Abstract Talatisamine ( 1 ) is a member of the C 19 ‐diterpenoid alkaloid family, and exhibits K + channel inhibitory and antiarrhythmic activities. The formidable synthetic challenge that 1 presents is due to its highly oxidized and intricately fused hexacyclic 6/7/5/6/6/5‐membered‐ring structure (ABCDEF‐ring) with 12 contiguous stereocenters. Here we report an efficient synthetic route to 1 by the assembly of two structurally simple fragments, chiral 6/6‐membered AE‐ring 7 and aromatic 6‐membered D‐ring 6 . AE‐ring 7 was constructed from 2‐cyclohexenone ( 8 ) through fusing an N‐ethylpiperidine ring by a double Mannich reaction. After coupling 6 with 7 , an oxidative dearomatization/Diels–Alder reaction sequence generated fused pentacycle 4 b . The newly formed 6/6‐membered ring system was then stereospecifically reorganized into the 7/5‐membered BC‐ring of 3 via a Wagner–Meerwein rearrangement. Finally, Hg(OAc) 2 induced an oxidative aza‐Prins cyclization of 2 , thereby forging the remaining 5‐membered F‐ring. The total synthesis of 1 was thus accomplished by optimizing and orchestrating 33 transformations from 8 .",10.1002/anie.201912737,2019-11-02,0.5871773908352859
Tetrahedron,Studies towards the total synthesis of novel marine diterpene havellockate. Construction of the tetracyclic core,,10.1016/s0040-4039(01)01721-x,2001-11-01,0.5871752569049873
Organic Letters,"Facile, Selective, and Regiocontrolled Synthesis of Oxazolines and Oxazoles Mediated by ZnI<sub>2</sub> and FeCl<sub>3</sub>",An expedient method for a direct approach to the selective and regiocontrolled synthesis of 2-oxazolines and 2-oxazoles mediated by ZnI(2) and FeCl(3) is described. A Lewis acid promoted cyclization of acetylenic amide with various functionalities was well tolerated to give 2-oxazolines and 2-oxazoles in good to excellent yields under mild reaction conditions.,10.1021/ol301980g,2012-08-09,0.5871706949759211
Organic Letters,"Stereoselective Synthesis of the C1–C9 and C11–C25 Fragments of Amphidinolides C, C2, C3, and F","An efficient synthesis of the C1-C9 and the C11-C25 fragments of amphidinolides C, C2, C3, and F from a common intermediate is reported. The construction of the C1-C9 fragment involves an intramolecular hetero-Michael cyclization to form the 3,5-disubstituted trans-tetrahydrofuran moiety. The approach to prepare the C11-C25 fragment utilizes a highly stereoselective aerobic cobalt-catalyzed alkenol cyclization and a chelated Mukaiyama aldol reaction to form the C13-C14 bond and to concomitantly install the C13 hydroxyl group.",10.1021/acs.orglett.7b00217,2017-02-23,0.5871646455243678
Tetrahedron,A new synthesis of macrocyclic keto-lactones via ring expansion of 2-(3-hydroxypropyl)-2-nitrocycloalkanones,,10.1016/s0040-4039(00)87658-3,1982-01-01,0.5871622301755977
Journal of the American Chemical Society,Total Synthesis and Assignment of Configuration of Lissoclinamide 7,"The first total synthesis of lissoclinamide 7, a 21-membered cyclopeptide isolated from Lissoclinum bistratum, was accomplished in 23 steps and 4.4% overall yield. The extraordinary configurational lability of the thiazoline segments was overcome by a novel strategy combining the use of the Burgess reagent for multiple simultaneous oxazoline and thiazoline formations and an efficient oxazoline → thiazoline heterocycle interconversion. In addition to the total synthesis, this work highlights the scope of alternative strategies toward Lissoclinum peptides and presents the preparation of analogues for SAR studies of the cytotoxic effects of this family of marine natural products.",10.1021/ja962859f,1996-01-01,0.5871614318036733
Organic Letters,"Two Convergent Routes to the Left-Wing Fragment of Ciguatoxin CTX3C Using <i>O</i>,<i>S</i>-Acetals As Key Intermediates","Ciguatoxins, principal causative toxins of ciguatera seafood poisoning, are large ladderlike polycyclic ethers. Here, we report two convergent routes to synthesis of the multiolefinic left half of ciguatoxins based on a newly developed acyl radical strategy. Remarkably, only 13 steps from the monocyclic E-ring were required to construct the left wing. [reaction: see text]",10.1021/ol062350h,2006-11-07,0.5871601731629863
Tetrahedron,Practical stereocontrolled synthesis of 2-functionalized-methyl-1β-methylcarbapenems,,10.1016/s0040-4039(00)73360-0,1994-06-01,0.5871479303528775
Tetrahedron,New synthesis of DL-α- aminoacids from t-butyl N(diphenylmethylene) oxamate,,10.1016/s0040-4039(00)99404-8,1989-01-01,0.5871435696785917
Angewandte Chemie International Edition,"Synthesis of the (9S,18R) Diastereomer of Cyclamenol A","A vanadium-mediated pinacol coupling reaction was the key step in the synthesis of the polyene macrolactam (9S,18R)-cyclamenol A (1). The natural diastereomer (configuration not known) inhibits the adhesion of leukocytes to endothelial cells, a key event in the response to inflammation, tissue injury, and infection.",10.1002/(sici)1521-3773(20000317)39:6<1125::aid-anie1125>3.0.co;2-o,2000-03-17,0.5871386084279622
Tetrahedron,Novel isomerization of dibenzocyclooctadiene lignan lactone —first synthesis of (±)-stegane—,,10.1016/s0040-4039(01)86163-3,1979-01-01,0.5871372910308225
Tetrahedron,"Enantioselective synthesis of 5-substituted- and 3,5-disubstituted-2-formylpyrrolidine derivatives, the key D-ring fragments of (−)-quinocarcin and (−)-10-decarboxyquinocarcin",,10.1016/s0040-4039(00)73849-4,1993-09-01,0.587133907904743
Synthesis,"Diastereoselective Syntheses of N-Protected Derivatives of 1α,5α,6β-6-Amino-3-azabicyclo[3.1.0]hexane; A Route to Trovafloxacin 6β-Diastereomer","(opens in new window) Buy Article (opens in new window) Permissions and Reprints (opens in new window) All articles of this category (opens in new window) trovafloxacin 6 β -diastereomer - synthesis - chloroenamines - N -protected 1 α ,5 α ,6 β -6-amino-3-azabicyclo[3.1.0]hexanes",10.1055/s-1998-2055,1998-05-01,0.5871325096871293
Organic Letters,Four-Component Benzyne Coupling Reactions: A Concise Total Synthesis of Dehydroaltenuene B,"A four-component coupling reaction of 3,5-dimethoxybenzyne with 2-methyl-2-cyclohexenylmagnesium chloride, carbon dioxide, and iodine was utilized as a key step in the first total synthesis of dehydroaltenuene B.",10.1021/ol8015435,2008-08-02,0.5871212739859286
Synlett,"Synthesis of 3-Amino-2-carboxamide Tetrahydropyrrolo[2,3-b]quinolines","This article communicates the first synthesis of 3-amino-2-carboxamide pyrrolo[2,3- b ]quinolines and fused-ring pyrrolopyridines in an efficient synthesis via a Thorpe–Ziegler transformation. The reported synthetic route allows for a wide range of nitrogen analogues of thienopyridines – compounds which have potent bioactivities but poor aqueous solubility.",10.1055/s-0036-1588619,2016-10-11,0.5871131668357696
Journal of Organic Chemistry,Asymmetric Synthesis of the HMG-CoA Reductase Inhibitor Atorvastatin Calcium: An Organocatalytic Anhydride Desymmetrization and Cyanide-Free Side Chain Elongation Approach,An efficient asymmetric synthesis of atorvastatin calcium has been achieved from commercially available diethyl 3-hydroxyglutarate through a novel approach that involves an organocatalytic enantioselective cyclic anhydride desymmetrization to establish C(3) stereogenicity and cyanide-free assembly of C7 amino type side chain via C5+C2 strategy as the key transformations.,10.1021/jo402829b,2014-02-27,0.5871093408332108
Synlett,Asymmetric Synthesis of D-Fucosamine and <i>N</i>-Methyl-D-Fucosamine,"All articles of this category (+)-D-fucosamine and (+)- N -methyl-D-fucosamine (the amino sugar moiety of neocarzinostatin) have been synthesized from known building blocks derived from natural amino acids. Direct and diastereoselective construction of the key intermediate 4 was accomplished by a syn -aldol type reaction between Schöllkopf's bislactim ether 2 and the 1,3-dioxolane-4-carboxaldehyde 3 . Reduction and monomethylation of a O'Donnell's Schiff base derived from the common amino ester 7 allows an optional access to the N -methyl derivative. 2-amino-2,6-dideoxy-galactose - neocarzinostatin - amino acid based synthesis - syn -aldol addition",10.1055/s-1997-696,2004-03-22,0.5871080044704534
Tetrahedron,"Synthesis of alkenoic acid derivatives containing cyclopropane ring, new juvenile hormone analogs",,10.1016/s0040-4039(00)99009-9,1985-01-01,0.5870994792013855
Organic Process Research & Development,Multikilogram Synthesis of a Hepatoselective Glucokinase Activator,"This work describes the process development and manufacture of early-stage clinical supplies of a hepatoselective glucokinase activator, a potential therapy for type 2 diabetes mellitus. Critical issues centered on challenges associated with the synthesis of intermediates and API bearing a particularly racemization-prone α-aryl carboxylate functionality. In particular, a T3P-mediated amidation process was optimized for the coupling of a racemization-prone acid substrate and a relatively non-nucleophilic amine. Furthermore, an unusually hydrolytically-labile amide in the API also complicated the synthesis and isolation of drug substance. The evolution of the process over multiple campaigns is presented, resulting in the preparation of over 110 kg of glucokinase activator.",10.1021/op300194c,2012-08-31,0.5870941107486454
Organic Letters,<i>Pseudo</i>-<i>C</i><i><sub>3</sub></i>-Symmetric Tertiary Alcohol Building Block via Group-Selective Hydroalumination:  A Synthesis of (−)-Malyngolide,"The stereocontrolled preparation of tertiary alcohol 4 and its TMS surrogate 5, which share a pseudo-C(3)()-symmetry, is described. Compound 4 was used for the synthesis of (-)-malyngolide.",10.1021/ol015943v,2001-05-01,0.587089128813557
Tetrahedron,"Synthetic applications of 2-(1,3-dithian-2-yl)indoles. Synthesis of 1-methyl-15-hydroxy-20-deethyldasycarpidone",,10.1016/s0040-4039(00)70670-8,1989-01-01,0.5870887857690815
Tetrahedron,Synthesis of a first thiophene containing analog of the HIV protease inhibitor nelfinavir,,10.1016/j.tetlet.2004.02.026,2004-02-27,0.5870873840934063
Angewandte Chemie International Edition,Tetramic Acid Antibiotics: Stereoselective Synthesis of Streptolic Acid and Tirandalydigin,"A new and promising methodology for the synthesis of the tetramic acid family of antibiotics was developed. The first synthesis of N-2,4-dimethoxybenzyl tirandalydigin (1), as well as a synthesis of streptolic acid (2), was achieved in a highly stereoselective manner.",10.1002/anie.200462300,2005-01-28,0.587080896342997
Tetrahedron,"Novel and stereocontrolled asymmetric synthesis of a new naturally occurring styryllactone, (+)-cardiobutanolide",,10.1016/j.tetlet.2005.12.113,2006-01-20,0.5870802315090284
Organic Letters,Synthesis of Substituted Imidazoles via Organocatalysis,A one-pot synthesis of substituted imidazoles is described. The cornerstone of this methodology involves the thiazolium-catalyzed addition of an aldehyde to an acyl imine to generate the corresponding alpha-ketoamide in situ followed by ring closure to the imidazole in a one-pot sequence. The extension of this methodology to the one-pot synthesis of substituted oxazoles and thiazoles is also described. [reaction: see text],10.1021/ol0498803,2004-02-11,0.5870776092382682
Journal of the American Chemical Society,A Convergent Stereoselective Synthesis of Quinolizidines and Indolizidines: Chemoselective Coupling of 2-Hydroxymethyl-Substituted Allylic Silanes with Imines,"A convergent synthesis of stereodefined indolizidines and quinolizidines through chemoselective allyl transfer between 2-hydroxymethyl-substituted allylic silanes and imines is described. Overall, highly substituted heterocycles that contain three stereogenic centers and up to four fused rings can be accessed in two steps from relatively simple coupling partners.",10.1021/ja908504z,2009-11-12,0.5870755060174513
European Journal of Organic Chemistry,"Synthesis of Both Enantiomers of Diastereomeric 4‐Fluoro‐4,5‐Dihydroceramides","Abstract Two diastereomeric enantiopure 4‐fluoro‐4,5‐dihydroceramides with the natural D ‐ erythro configuration at the 2‐ and 3‐carbon atoms have been synthesized in an enantioselective eleven‐step sequence. The key step of the synthesis was a diastereoselective asymmetric Sharpless dihydroxylation of ethyl trans ‐4‐fluorooctadec‐2‐enoate ( 8 ) with AD‐mix‐β to afford the D ‐ erythro arrangement. The diastereomers of the other enantiomeric series were synthesized analogously with the use of AD‐mix‐α. In all cases, the nitrogen heteroatom was introduced into the 2‐position by regio‐ and stereoselective ring opening of cyclic sulfates 13 and 14 with azide. Staudinger reduction, acylation of the intermediary formed amino group, chromatographic separation of the diastereomers and chemoselective reduction of the ester functionality with sodium borohydride in the presence of methanol afforded both title compounds in an enantiopure form. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2006)",10.1002/ejoc.200600456,2006-08-18,0.5870721410401979
Tetrahedron,An efficient one-step synthesis of fulleroisoxazolines and fulleropyrazolines mediated by (diacetoxyiodo)benzene,,10.1016/j.tetlet.2010.09.038,2010-09-18,0.5870699984863345
Tetrahedron,Palladium catalyzed [2+2+1] cyclotrimerization of alkynes: selective synthesis of fulvenes,,10.1016/s0040-4039(00)00075-7,2000-03-01,0.5870617603372751
Tetrahedron,Synthesis of new N-heterocycles; intramolecular ring closure with imines,,10.1016/s0040-4039(98)00668-6,1998-06-01,0.5870600977272536
Journal of Organic Chemistry,Asymmetric Total Synthesis of an Important 3-(Hydroxymethyl)carbacephalosporin,"Carbacephalosporins have gained much attention as important antibacterial agents. Recently, 3-(hydroxymethyl)carbacephalosporins have been linked to quinolones for the production of multifunctional antibiotics. A short, practical asymmetric total synthesis of carbacephalosporin 3, suitable for conjugating to other chemical moieties, is reported. The synthesis was achieved by Mitsunobu cyclization of dipeptide 12, prepared from l - erythro - anti -β-hydroxy-α-amino acid 11, and subsequent Horner−Wadsworth−Emmons cyclization of ketone 16 .",10.1021/jo971772p,1998-01-30,0.5870574476509037
Journal of Organic Chemistry,Process Research and Development for a Tetrazole-Based Growth Hormone Secretagogue (GHS) Pharmaceutical Development Candidate,"BMS-317180 (1) is a potent, orally active agonist of the human growth hormone secretagogue (GHS) receptor. This manuscript details the process research and development efforts that enabled the synthesis of the phosphate salt of 1 on a multi-kilogram scale. Key considerations in the development of this process focused on safe execution and the requirement for telescoped synthetic transformations (i.e., without isolation of intermediate products) to contend with a lack of suitably crystalline products.",10.1021/jo9003508,2009-04-24,0.5870560121978446
Synlett,Synthesis of 2-epi-Pumiliotoxin C via a Challenging Intramolecular Hydroamination Key Step,"The synthesis of 2-epi-pumiliotoxin C was achieved in ten steps from cyclohexadiene oxide, using a challenging Cope-type hydroamination key step. This cyclization was performed on a mixture of two epimeric hydroxylamines, and a boat transition state is proposed to explain the kinetic preference observed for the cyclization of the epimer leading to N-hydroxy-epipumiliotoxin C.",10.1055/s-0028-1088146,2009-03-20,0.5870387845582281
Journal of the American Chemical Society,"Synthesis of Axially Chiral 2,2′-Bisphosphobiarenes via a Nickel-Catalyzed Asymmetric Ullmann Coupling: General Access to Privileged Chiral Ligands without Optical Resolution","-(iodo)arylphosphonates resulting in highly enantioenriched axially chiral bisphosphine oxides and bisphosphonates. These products are readily converted to enantioenriched biaryl bisphosphines without need for chiral auxiliaries or optical resolution. This provides a practical route for the development of previously uninvestigated atroposelective biaryl bisphosphine ligands. The conditions have also proven effective for asymmetric dimerization of other, non-phosphorus-containing aryl halides.",10.1021/jacs.0c12843,2021-01-13,0.5870385725000099
Synthesis,"Practical, Efficient Synthesis of β-Amino Tertiary Thiols via Aminolysis Ring-Opening of Thiiranes",,10.1055/s-1999-3516,1999-07-01,0.5870379111368319
Tetrahedron,New development of a common glucosamine disaccharide intermediate with chemically differentiated two amino and six hydroxyl groups for lipid a syntheses and a formal synthesis of Salmonella mutant lipid A.,,10.1016/s0040-4039(00)84384-1,1986-01-01,0.5870368192187757
Synlett,"Transition Metals in Organic Synthesis, Part 91:¹ Palladium-Catalyzed Approach to 2,6-Dioxygenated Carbazole Alkaloids - First Total Synthesis of the Phytoalexin Carbalexin C","The palladium(0)-catalyzed C-N bond formation and palladium(II)-catalyzed oxidative cyclization provide an efficient route to a series of 2,6-dioxygenated carbazole alkaloids including the first total synthesis of the phytoalexin carbalexin C.",10.1055/s-0029-1217810,2009-08-07,0.5870355658937824
Tetrahedron,A novel method for the upper rim alkoxy-substitution of calix[4]arene via a bis(spirodienone) route,,10.1016/j.tetlet.2008.11.118,2008-12-05,0.5870341607234063
Organic Letters,Total Synthesis of (+)-Cocaine via Desymmetrization of a <i>meso</i>-Dialdehyde,"[reaction: see text] The total synthesis of (+)-cocaine is described. An extension of the recently reported proline catalyzed intramolecular enol-exo-aldol reaction to a meso-dialdehyde provided the tropane ring skeleton directly with good enantiomeric excess. The meso-dialdehyde was prepared using a 2-azaallyllithium [3 + 2] cycloaddition to generate a cis-2,5-disubstituted pyrrolidine. Overall, the synthesis proceeded in 6.5% yield and 86% ee over 14 linear steps starting from commercially available 3-benzyloxy-1-propanol.",10.1021/ol048777a,2004-08-19,0.5870228142256161
Organic Letters,"Total Synthesis of Racemic Thieno[3,2-<i>f</i>]thiochromene Tricarboxylate, a Luciferin from Marine Polychaeta <i>Odontosyllis undecimdonta</i>","We report the first total synthesis of racemic Odontosyllis undecimdonta luciferin, a thieno[3,2- f ]thiochromene tricarboxylate comprising a 6-6-5-fused tricyclic skeleton with three sulfur atoms in different electronic states. The key transformation is based on tandem condensation of bifunctional thiol-phosphonate, obtained from dimethyl acetylene dicarboxylate, with benzothiophene-6,7-quinone. The presented convergent approach provides the synthesis of the target compound with a previously unreported fused heterocyclic core in 11 steps, thus allowing for unambiguous confirmation of the chemical structure of Odontosyllis luciferin by 2D-NMR spectroscopy.",10.1021/acs.orglett.3c01696,2023-06-27,0.5870217468862647
Angewandte Chemie International Edition,Total Synthesis of the Indole Alkaloid (±)‐ and (+)‐Methyl <i>N</i>‐Decarbomethoxychanofruticosinate,"All caged up: The first total synthesis of N-decarbomethoxychanofruticosinate is achieved by using a SmI2 -mediated intramolecular Reformatsky-like reaction to create the seven-membered ring, and an intramolecular oxidative coupling to install the caged and strained ring system.",10.1002/anie.201307788,2013-11-20,0.5870131636879764
Tetrahedron,"Regioselective two step synthesis of 3-substituted 2-aminoimidazo[1,2-a]pyrimidines",,10.1016/j.tetlet.2006.11.181,2007-01-14,0.5870110801552414
Journal of Organic Chemistry,"Asymmetric Synthesis of 3,4-Disubstituted 2-(Trifluoromethyl)pyrrolidines through Rearrangement of Chiral 2-(2,2,2-Trifluoro-1-hydroxyethyl)azetidines","Enantiopure 4-formyl-β-lactams were deployed as synthons for the diastereoselective formation of chiral 2-(2,2,2-trifluoro-1-hydroxyethyl)azetidines via trifluoromethylation through aldehyde modification followed by reductive removal of the β-lactam carbonyl moiety. Subsequent treatment of the (in situ) activated 2-trifluoroethylated azetidines with a variety of nitrogen, oxygen, sulfur, and fluorine nucleophiles afforded chiral 3,4-disubstituted 2-(trifluoromethyl)pyrrolidines in good to excellent yields (45–99%) and high diastereoselectivities (dr >99/1, 1 H NMR) via interception of bicyclic aziridinium intermediates. Furthermore, representative pyrrolidines were N,O-debenzylated in a selective way and used for further synthetic elaboration to produce, for example, a CF 3 -substituted 2-oxa-4,7-diazabicyclo[3.3.0]octan-3-one system.",10.1021/acs.joc.7b01241,2017-08-31,0.587006000710237
Tetrahedron,The Mitsunobu reaction of ortho-ethers of secondary benzylic alcohols. Concise enantioselective synthesis of a key intermediate of the novel β-adrenergic receptor antagonist MY336-a,,10.1016/0040-4039(96)01122-7,1996-07-01,0.5870038438744383
Tetrahedron,"Novel protection of 1,2-diol for trans-dihydroxycyclopentene ring construction by the C H insertion of alkylidene carbene: Formal total synthesis of (+)-trehazolin",,10.1016/j.tetlet.2019.151085,2019-08-27,0.5870031125427253
Tetrahedron,Wittig reaction: A new route to α-methoxyketones. Application to the synthesis of simplified analogs of artemisinin,,10.1016/s0040-4039(98)00688-1,1998-06-01,0.5870014369995561
Tetrahedron,"Structure and total synthesis of deplancheine, a novel indoloquinolizidine alkaloid",,10.1016/s0040-4039(00)93625-6,1980-01-01,0.5869985532023486
Synlett,Synthetic Studies on Pancratistatin. Construction of the Phenanthridone Ring System via a Hydrogen Bond Controlled Enamide Photocyclization,All articles of this category Synthesis of the phenanthridone core of the antineoplastic alkaloid pancratistatin is reported. The key step is a regiocontrolled aryl enamide photocyclization that produces the trans-BC ring fusion characteristic of the natural product. pancratistatin - phenanthridone - enamide - photocyclization - hydrogen-bonding,10.1055/s-1995-5266,1995-06-01,0.5869878216966795
Journal of the American Chemical Society,Asymmetric Total Synthesis of (+)-Milbemycin D,"The enantioselective total synthesis of the potent antiparasitic agent milbemycin D ( 1 ) has been achieved. The spiroketal fragment is prepared through a novel spiroketalization of a hydroxy pyrone to set the anomeric stereocenter and establish functionality for the stereocontrolled attachment and subsequent extension of the connecting chain between the spiroketal and the hexahydrobenzofuran fragment. The hexahydrobenzofuran fragment is constructed through the exploitation of a sequential electrophilic cyclization−[2,3]-sigmatropic rearrangement to close the oxygen-containing ring and incorporate the C5 hydroxyl. A lithium bromide accelerated Wittig olefination joins the spiroketal-containing subunit and the hexahydrobenzofuran subunit at the C10,11 double bond in high yield. Subsequent oxidation of the C1 hydroxyl provides access to the seco acid, which smoothly undergoes macrolactonization. The sensitive C2 stereochemistry and the C3,4 double bond are incorporated without epimerization at C2 or migration of the C3,4 double bond.",10.1021/ja961071u,1996-01-01,0.5869833002520648
Journal of Organic Chemistry,Synthesis of Quillaic Acid through Sustainable C–H Bond Activations,"High Resolution Image Download MS PowerPoint Slide To meet the demand for quillaic acid, a multigram synthesis of quillaic acid was accomplished in 14 steps, starting from oleanolic acid, leading to an overall yield of 3.4%. Key features include C–H activation at C-16 and C-23. Through Pd-catalyzed C–H acetoxylation, the oxidation at C-23 was observed as the major product, as opposed to at C-24. A copper-mediated C–H hydroxylation using O 2 successfully afforded the single isomer, 16β-ol triterpenoid, followed by configuration inversion to the desired 16α-ol compound. In summary, with steps optimized and conducted on a multigram scale, quillaic acid could be feasibly acquired through C–H activation with inexpensive copper catalysts, promoting a more sustainable approach.",10.1021/acs.joc.3c02958,2024-04-10,0.5869827414872142
Synlett,A Direct Carbometallation-StereoselectiveCycloaddition-Ring Closing Metathesis Route to the TricyclicABC Core of Taxoids,"The synthesis of the tricyclic ABC ring-system of Taxol® (paclitaxel) is described. This direct route involves sequential reactions employing the carbometallation of a propargyl alcohol, followed by a cis-alkene tether controlled stereoselective intramolecular Diels-Alder reaction to generate the AB-ring system and ring closing metathesis (RCM) of the pendant allyl substituents to construct the C ring.",10.1055/s-2003-40358,2003-06-30,0.5869760958360627
Angewandte Chemie International Edition,Evaluation of Diene Hierarchies for Diels-Alder Reactions En Route to Xestocyclamine A: Elaboration of an Ansa Bridge by<i>B</i>-Alkyl Suzuki Macrocyclization,"A double Michael addition of amine 2 to 1 was a key reaction in the synthesis of the isoquinuclidine core 4 of xestocyclamine A, a protein kinase C inhibitor. The first ansa bridge was formed efficiently by a B-alkyl Suzuki coupling in 3. TBDPS = tert-butyldiphenylsilyl; Ts = p-toluenesulfonyl.",10.1002/1521-3773(20020503)41:9<1581::aid-anie1581>3.0.co;2-f,2002-05-02,0.5869738761472653
Tetrahedron,"A novel route to 3-alkylated estra-1,3,5(10)-trienes",,10.1016/s0040-4039(00)86669-1,1988-01-01,0.5869673326721564
Tetrahedron,"Synthesis of a novel heterocyclic ring system: 2-thia-3,5,6,7,9-pentaazabenz[cd]azulenes",,10.1016/s0040-4039(01)02222-5,2002-01-01,0.5869660823278924
Tetrahedron,"Novel syntheses of camptothecin alkaloids, part 2. concise synthesis of (S)-camptothecins",,10.1016/0040-4039(96)01205-1,1996-08-01,0.5869575304563339
Journal of Organic Chemistry,Convenient Synthesis of an A-Ring Aromatic Trichothecene Analog,"A short and convenient route to the synthesis of A-ring aromatic trichothecene analogue 2 is described, employing a cyclobutyl carbinol rearrangement as the key step. Cycloaddition of ethylene to the methoxychromone 6 furnished the oxetanol 7 along with some cycloadduct 8, the latter arising from cleavage of 7 . Lithium aluminum hydride reduction of 7 to the diol 9 followed by acid-catalyzed rearrangement afforded the benzooxabicyclo[3.2.1]octanone 10, through exclusive external bond migration. Interaction of 10 with dimethyloxosulfonium methylide furnished the desired anti-epoxide 2, whereas dimethyl sulfonium methylide yielded the syn-epoxide 12 . Reduction of these epoxides provided the alcohols 13 and 14, respectively. Addition of methylmagnesium iodide to ketone 10 furnished exclusively alcohol 14, supporting the stereoassignments.",10.1021/jo971970g,1998-05-19,0.5869523161508375
Angewandte Chemie International Edition,Pd‐Catalyzed Selective Carbonylation of <i>gem</i>‐Difluoroalkenes: A Practical Synthesis of Difluoromethylated Esters,"Abstract The first catalyst for the alkoxycarbonylation of gem ‐difluoroalkenes is described. This novel catalytic transformation proceeds in the presence of Pd(acac) 2 /1,2‐bis((di‐ tert ‐butylphosphan‐yl)methyl)benzene (btbpx) ( L4 ) and allows for an efficient and straightforward access to a range of difluoromethylated esters in high yields and regioselectivities. The synthetic utility of the protocol is showcased in the practical synthesis of a Cyclandelate analogue using this methodology as the key step.",10.1002/anie.201813801,2019-02-19,0.586947293546108
Journal of Organic Chemistry,Sulfamidate-Based Stereoselective Total Synthesis of (+)-Preussin Using Gold(I)-Catalyzed Intramolecular Dehydrative Amination: Dead End and Detour,"A sulfamidate-based stereoselective total synthesis of (+)-preussin has been developed. The key step involves a gold(I)-catalyzed intramolecular dehydrative amination of sulfamate esters tethered to allylic alcohols, which allows for the construction of the cyclic sulfamidate with high stereoselectivity. Further manipulation to highly constrained bicyclic sulfamidate and the following ring-opening process afford 3-hydroxypyrrolidine motif stereoselectively. The energy of the constrained bicyclic ring system is relieved by the subsequent ring-opening process, which leads to a stereoselective formation of the 3-hydroxypyrrolidine motif under mild reaction conditions. The success of this approach not only provides a new method for the total synthesis of enantiomerically pure (+)-preussin but also highlights the synthetic utility of sulfamidates in constructing valuable natural product architectures.",10.1021/acs.joc.3c00670,2023-07-01,0.5869389928984072
Synthesis,"Diastereo- and Enantioselective Synthesis of 2-Substituted 1-Aminocyclopropane-1-Carboxylic Acids. Application to the Synthesis of Protected 2,3-Methano Analogs of Ornithine and Glutamic Acid","An enantiodivergent synthesis of protected 2,3-methano amino acid analogs is described. (R)-2-benzyloxyethyloxirane, prepared from (S)-aspartic acid, was reacted with tert-butyl hydrogen malonate and further transformed into an enantiomeric pair of intermediate cyclopropane-fused-lactones, 1-carboxy-2-oxo-3-oxabicyclo[4.1.0]heptane. Each of these enantiomers allowed differentiation of the carboxy functions and generation of a 2-hydroxyethyl group on the cyclopropanes, thus affording access to any or all four stereoisomers. The two-carbon pendant allowed for the direct synthesis of protected 2,3-methano analogs of glutamic acid and ornithine and can be used for other useful transformations.",10.1055/s-2005-870007,2005-01-01,0.5869334924498604
Tetrahedron,A convenient synthetic route to a useful synthon: 4-bromo-2-pyridinecarboxaldehyde,,10.1016/j.tetlet.2008.10.027,2008-10-15,0.5869293478121399
Organic Letters,"Asymmetric Catalysis Route to <i>anti</i>,<i>anti</i> Stereotriads, Illustrated by Applications","A short sequence based on asymmetric catalysis, chirality transfer, and an optimized carbometallation protocol gave an anti,anti stereotriad building block in six steps. Both enantiomers of the chirality source, N-methyl ephedrine, are inexpensive, and the auxiliary is recoverable. In one chiral series, the building block was converted to the ""B-2"" intermediate in Miyashita's synthesis of scytophycin C; in the enantiomeric series, it was converted to a key intermediate for aplyronine A and to the polyketide ""cap"" for the callipeltins.",10.1021/ol702989g,2008-03-04,0.5869275389624206
Synthesis,New [<i>f</i>]-Fused Theophyllines via Intramolecular Nucleophilic Addition of Alkyl (<i>E</i>)-4-[(8-Substituted)theophyllin-7-yl]-2-butenoate,"All articles of this category A simple synthetic route to [ f ]-annulated theophyllines ([ f ]-annulated 3,7-dihydro-1,3-dimethyl-1 H -purine-2,6-diones) is described, based on intramolecular nucleophilic addition, and starting from ethyl ( E )-4-[(8-substituted) theophyllin-7-yl]-2-butenoates. The presence of an 8-hydroxymethyl group enables the formation of hexahydro-9 H -[1,4]oxazino[3,4- f ]purine derivatives 3a , in the case of an 8-methylthio substituent, 8 , the products are hexahydro- 9 H -[1,4]thiazino[3,4- f ]purine 9 , and similarly with 8-hydrazino derivatives 12 , octahydro[1,2,4]triazino[3,4- f ]purines 14 are obtained.",10.1055/s-1991-26529,1991-01-01,0.5869205728515696
Tetrahedron,Studies on the total synthesis of the macrolide antitumor agent rhizoxin. 1. Synthesis of the C3C13 segment,,10.1016/s0040-4039(97)01780-2,1997-10-01,0.586914171371955
Tetrahedron,Studies on the total synthesis of the macrolide antitumor agent rhizoxin. 2. Synthesis of the C14C26 segment,,10.1016/s0040-4039(97)01781-4,1997-10-01,0.586914171371955
Journal of Organic Chemistry,Chemoenzymatic Synthesis of Enantiopure 1-Azafagomine,A new chemoenzymatic synthesis of both enantiomeric forms of the glycosidase inhibitor 1-azafagomine ( 1 ) is reported. The synthesis starts from the achiral starting materials pentadienol and methylurazol with the key steps being a hetero-Diels−Alder reaction followed by a lipase R/Novozym 435-catalyzed enantioselective esterification of the Diels−Alder adduct.,10.1021/jo9907989,1999-10-22,0.5869134266446028
Synlett,"Stereoselective Synthesis of (-)-Swainsonine and 1,2-di-<i>epi</i>-Swainsonine from γ-Hydroxy-α,β-unsaturated Sulfones","All articles of this category Efficient and stereodivergent syntheses of (-)-swainsonine and 1,2-di- epi -swainsonine starting from the readily available enantiomerically pure γ-hydroxy-α,β-unsaturated sulfone ( R )- 2 are described. The stereoselectivity in the osmium-dihydroxylation step of the unsaturated indolizidines 8 was highly dependent on the substitution at C8. 1,2-di- epi -swainsonine was found to be a good inhibitor of α-d-mannosidase (jack bean). swainsonine - sulfones - stereoselectivity - glycosidase inhibitors - lipases",10.1055/s-2000-6455,2000-01-01,0.5869110231777888
Tetrahedron,"Asymmetric synthesis. XXXIII. Diastereoselective alkylation of N,N-substituted amides",,10.1016/0040-4039(94)85366-5,1994-09-01,0.5869030948202468
European Journal of Organic Chemistry,Synthesis of Berkeleylactone A by Ring‐Closing Alkyne Metathesis,"Abstract A new route to the macrolactone antibiotic berkeleylactone A was developed. As a key step, a ring‐closing alkyne metathesis (RCAM) of an ester substrate featuring 1‐propynyl termini was used. The carboxylic part of the substrate was easily assembled using alkyne chemistry, like carboxylation of a diyne followed by isomerization of the ynoate section to a dienoate and dihydroxylation of the 4,5‐double bond. The synthesis of the alcohol part of the ester started with opening of ( R )‐propylene oxide with an acetylide and was followed by two triple bond migrations. After successful RCAM which formed the C8−C9 bond, the triple bond was selectively hydrogenated to the corresponding alkene before the 4,5‐diol was oxidized to the 5‐hydroxy‐4‐oxo derivative. At this stage, the thioether was formed and the 8,9‐double bond reduced. We also prepared the 8,9‐didehydro analog of berkeleylactone A. However, it turned out that its antimicrobial activity was slightly reduced.",10.1002/ejoc.202300615,2023-07-27,0.586902492838432
Synthesis,"A Novel One-Step Synthesis of 2-Methoxycarbonylthieno[2,3-<i>b</i>]quinolines and 3-Hydroxy-2-methoxycarbonyl-2,3-dihydrothieno[2,3-<i>b</i>]-quinolines",Syntheses a partir de chloro-2 quinoleinecarbaldehydes-3 par l'intermediaire d'acyl-3 chloro-2 quinoleines,10.1055/s-1984-30929,1984-01-01,0.5869006223154347
Tetrahedron,Total synthesis of lycoperdic acid and its C4-epimer,,10.1016/j.tetlet.2019.06.067,2019-06-29,0.5869004032963315
Tetrahedron,Total synthesis of alternaric acid,,10.1016/s0040-4039(00)77605-2,1993-04-01,0.5869004032963315
Tetrahedron,Total synthesis of (+)-zaragozic acid C,,10.1016/s0040-4039(98)00485-7,1998-05-01,0.5869004032963315
Tetrahedron,A total synthesis of (±)--kainic acid,,10.1016/s0040-4039(00)84889-3,1986-01-01,0.5869004032963315
Tetrahedron,First total synthesis of (+)-pentandranoic acid A,,10.1016/j.tetlet.2012.04.080,2012-04-24,0.5869004032963315
Tetrahedron,Total synthesis of (±)-gibberellic acid,,10.1016/s0040-4039(00)95293-6,1989-01-01,0.5869004032963315
Tetrahedron,Total synthesis of (−)-martinellic acid,,10.1016/j.tetlet.2007.02.008,2007-02-08,0.5869004032963315
Tetrahedron,Total synthesis of (±)-rhopaloic acid A,,10.1016/s0040-4039(97)01220-3,1997-08-01,0.5869004032963315
Tetrahedron,Total synthesis of lipoxins A4 and B4 from d-isoascorbic acid,,10.1016/s0040-4039(00)92034-3,1991-02-01,0.5869004032963315
Tetrahedron,Total synthesis of (+)-bongkrekic acid,,10.1016/j.tetlet.2004.09.162,2004-10-21,0.5869004032963315
Tetrahedron,"Total synthesis of (±)-α,γ-onoceradienedione and lansic acid",,10.1016/s0040-4039(01)91122-0,1984-01-01,0.5869004032963315
Tetrahedron,Total synthesis of (+)-galantinic acid,,10.1016/s0040-4039(01)93434-3,1989-01-01,0.5869004032963315
Tetrahedron,Formal total synthesis of (±)-martinellic acid,,10.1016/j.tetlet.2005.01.004,2005-01-25,0.5869004032963315
Tetrahedron,Total synthesis of d1-hirsutic acid,,10.1016/s0040-4039(01)91998-7,1974-01-01,0.5869004032963315
Tetrahedron,Total synthesis of (+)-kaurene and (+)-phyllocladene from 1-abietic acid,,10.1016/s0040-4039(01)96032-0,1973-01-01,0.5869004032963315
Tetrahedron,A formal total synthesis of (±)-pseudomonic acid A,,10.1016/0040-4039(95)01590-e,1995-10-01,0.5869004032963315
Tetrahedron,First total synthesis of penmacric acid and its stereoisomer,,10.1016/j.tetlet.2006.11.146,2006-12-14,0.5869004032963315
Tetrahedron,"Total synthesis of (9S,12R,13S)-pinellic acid",,10.1016/j.tetlet.2006.11.004,2006-11-29,0.5869004032963315
Tetrahedron,The total synthesis of α-allokainic acid,,10.1016/s0040-4039(00)86004-9,1983-01-01,0.5869004032963315
Tetrahedron,Total synthesis of fomitellic acid B,,10.1016/j.tetlet.2009.09.088,2009-09-23,0.5869004032963315
Tetrahedron,First total synthesis of tuberonic acid,,10.1016/j.tetlet.2007.01.035,2007-01-16,0.5869004032963315
Tetrahedron,Total synthesis of (+)-prelog-djerassi lactonic acid,,10.1016/s0040-4039(01)82936-1,1981-01-01,0.5869004032963315
Tetrahedron,The total synthesis of 1-oxygenated eudesmane sesquiterpenes : (±) dihydroreynosin and (±) 1-oxocostic acid,,10.1016/s0040-4039(00)87308-6,1982-01-01,0.5869004032963315
Tetrahedron,Total synthesis of (±)-sterpuric acid,,10.1016/s0040-4039(00)96684-x,1987-01-01,0.5869004032963315
European Journal of Organic Chemistry,Total synthesis of dextro beta rhodomycinone dextro 1 deoxy beta rhodomycinone and dextro 1 deoxy gamma rhodomycinone by incorporation of s alpha hydroxybutyric acid,,,1988-01-03,0.5869004032963315
Tetrahedron,A total synthesis of mycophenolic acid,,10.1016/s0040-4039(98)00423-7,1998-05-01,0.5869004032963315
Tetrahedron,Total synthesis of (+)-spiculoic acid A,,10.1016/j.tetlet.2009.02.101,2009-02-22,0.5869004032963315
Tetrahedron,A total synthesis of mycophenolic acid,,10.1016/s0040-4039(01)96954-0,1971-01-01,0.5869004032963315
Synthesis,Synthesis of 1-Trimethylsilylcycloalkenes from 1-Bromocycloalkenes by Wurtz-type Coupling,,10.1055/s-1980-29178,1980-01-01,0.5868979217108076
Synlett,One pot synthesis of halocetylenes from trimethylsilylacetylenes,,,1994-01-01,0.5868948060648147
Tetrahedron,"Selenosulfonation of 1,3-dienes: One-pot synthesis of 2-(phenylsulfonyl)-1,3-dienes",,10.1016/s0040-4039(00)80320-2,1988-01-01,0.5868948060648147
Synthesis,One-Pot Photolytic Synthesis of 1-Hydroxyfluorenes,,10.1055/s-1983-30241,1983-01-01,0.5868948060648147
Synthesis,A One-Pot Synthesis of Aziridines from 2-Aminoethanols,,10.1055/s-1984-31041,1984-01-01,0.5868948060648147
Tetrahedron,Biomimetic One-Pot Synthesis of Nucleotide Phosphates,,10.1016/s0040-4039(00)85856-6,1982-01-01,0.5868948060648147
Tetrahedron,‘One-pot’ biomimetic synthesis o dihydromancunine.,,10.1016/s0040-4039(00)93795-x,1976-05-01,0.5868948060648147
Tetrahedron,A one pot synthesis of annulated carbazole analogs,,10.1016/j.tetlet.2008.07.036,2008-07-10,0.5868948060648147
Tetrahedron,One-pot synthesis of carbohydrate thionolactones from 1-thiosugars,,10.1016/j.tetlet.2008.05.145,2008-06-05,0.5868948060648147
Tetrahedron,One-pot synthesis of 2-trifluoromethylchromones,,10.1016/j.tetlet.2011.01.045,2011-01-19,0.5868948060648147
Tetrahedron,One-pot synthesis of homotryptamines from indoles,,10.1016/j.tetlet.2004.03.070,2004-04-03,0.5868948060648147
Tetrahedron,"One-pot synthesis of 5-alkylthio-3H-1,2-dithiole-3-thiones",,10.1016/0040-4039(96)00209-2,1996-03-01,0.5868948060648147
Tetrahedron,One-pot synthesis of polyaza[n]naphthalenophanes and polyaza[n]anthracenophanes,,10.1016/s0040-4039(98)00587-5,1998-05-01,0.5868948060648147
Tetrahedron,Biomimetic one-pot synthesis of nucleotide phosphates,,10.1016/0040-4039(82)80145-7,1982-01-01,0.5868948060648147
Tetrahedron,One-pot synthesis of 2-phenylaminothiazolines from N-2-hydroxyethyl)-N′-phenylthioureas,,10.1016/s0040-4039(99)01704-9,1999-11-01,0.5868948060648147
Tetrahedron,One-pot synthesis of a thioureido-β-cyclodextrin dimer,,10.1016/s0040-4039(99)01313-1,1999-09-01,0.5868948060648147
Tetrahedron,One-pot synthesis of deoxyadenosine 3′-thiophosphates,,10.1016/s0040-4039(98)01669-4,1998-10-01,0.5868948060648147
Tetrahedron,One-pot synthesis of β-imidazolylpropionamides,,10.1016/j.tetlet.2008.04.096,2008-04-21,0.5868948060648147
Tetrahedron,"One-pot synthesis of polyfunctionalized α,β-unsaturated nitriles from nitroalkanes",,10.1016/j.tetlet.2003.09.211,2003-11-14,0.5868948060648147
Tetrahedron,"Corrigendum to ‘One-pot synthesis of polyfunctionalized α,β-unsaturated nitriles from nitroalkanes’",,10.1016/j.tetlet.2003.12.035,2003-12-30,0.5868948060648147
Tetrahedron,Corrigendum to “One-pot synthesis of 2-phenylamino-thiazolines from N-(2-hydroxyethyl)-N′-phenylthioureas”,,10.1016/s0040-4039(01)00133-2,2001-03-01,0.5868948060648147
Tetrahedron,One-pot synthesis of multivalent arrays of mannose mono- and disaccharides,,10.1016/s0040-4039(02)01855-5,2002-10-01,0.5868948060648147
Tetrahedron,One-pot synthesis of sulfamoylguanidines and sulfonylguanidines,,10.1016/s0040-4039(00)01410-6,2000-10-01,0.5868948060648147
Tetrahedron,The one-pot synthesis of amidonapthoquinones from aminonaphthoquinones,,10.1016/j.tetlet.2020.151800,2020-03-04,0.5868948060648147
Tetrahedron,"One pot synthesis of mono- and spirocyclic α-phosphonato-α,β-unsaturated cycloenones",,10.1016/s0040-4039(98)00460-2,1998-05-01,0.5868948060648147
Tetrahedron,One-pot synthesis of polysubstituted pyrimidines,,10.1016/j.tetlet.2005.01.068,2005-02-01,0.5868948060648147
Synthesis,A One-Pot Synthesis of Nitroenamines,,10.1055/s-1982-29768,1982-01-01,0.5868948060648147
Tetrahedron,One-pot synthesis of L-felinine,,10.1016/s0040-4039(99)00741-8,1999-06-01,0.5868948060648147
Journal of Organic Chemistry,Preparation of <i>cis</i>-γ-Hydroxycarvone Derivatives for Synthesis of Sesterterpenoid Natural Products: Total Synthesis of Phorbin A,"A robust synthetic approach to cis-γ-hydroxycarvone derivatives has been developed, enabling efficient access to synthetic building blocks for the growing family of bioactive sesterterpenoid natural products. Using this approach, an allyl bromide carvone derivative was used as the key building block for the total synthesis of the natural product phorbin A. This synthetic sequence also demonstrates the utility of benozyl enol ethers as an effective means of masking a β-ketophosphonate and their subsequent application in a one-pot benzoyl transfer-intramolecular Horner-Wadsworth-Emmons reaction.",10.1021/jo502748s,2015-01-28,0.5868925047671896
Organic Letters,Dipolar Cycloaddition of Novel 6-(Nitrileoxidomethyl) Penam Sulfone:  An Efficient Route to a New Class of β-Lactamase Inhibitors,"6-(Nitrileoxidomethyl) penam sulfone intermediate was prepared in a few steps starting from commercially available (+)-6-aminopenicillanic acid. This intermediate underwent smooth 1, 3-dipolar cycloaddition reactions with various alkenes and alkynes to give cycloadducts in moderate to good yields. By this new method, several potent beta-lactamase inhibitors were synthesized. The regio- and stereoselectivity outcomes of the cycloaddition process are also discussed.",10.1021/ol006256r,2000-09-08,0.5868908430571922
Journal of Organic Chemistry,A Short Stereoselective Preparation of Dienamides from Cyclobutene Compounds. Application in the Synthesis of a New Cyclohexene Nucleoside,"A short stereoselective synthesis of N-acylamino-1,3-dienes was developed starting from the cyclobutene lactam 8, which was obtained from 2-hydroxypyridine by a photochemical electrocyclic reaction. The tert-butoxycarbonyl derivative 17 was prepared to facilitate nucleophilic attacks to the carbonyl group, and the subsequent thermal ring opening provided dienes 18-21. One of these (20) was used in the synthesis of the cyclohexene nucleoside 30. A Diels-Alder reaction between diene 20 and maleic anhydride provided the endo-cycloadduct 22a. Three additional steps yielded amine 26. Construction of the uracil moiety afforded intermediate 29. Cyclization and removal of the protecting groups occurred in one step in the presence of ammonia, giving the target molecule 30. Diene 20 also underwent [4 + 2] cycloaddition with methyl acrylate to provide predominantly the endo-product 23a, regioselectively.",10.1021/jo001467v,2000-12-23,0.5868907959439408
Tetrahedron,"The preparation of (±) 18,19-epoxy-14,15,16-trisnorclerodan-13-oic acid as a key intermediate in the total synthesis of clerodane type diterpenes",,10.1016/0040-4039(80)88086-5,1980-01-01,0.5868888633219516
Journal of Organic Chemistry,"Granulatimide and Isogranulatimide, Aromatic Alkaloids with G2 Checkpoint Inhibition Activity Isolated from the Brazilian Ascidian <i>Didemnum </i><i>granulatum</i>:  Structure Elucidation and Synthesis","Crude methanol extracts of the ascidian Didemnum granulatum collected in Brazil showed activity in a new screen for G2 cell cycle checkpoint inhibitors. Bioassay-guided fractionation of the extract yielded the known alkaloids didemnimides A ( 1 ) and D ( 2 ), the new alkaloid didemnimide E ( 3 ), and a new G2 checkpoint inhibitor. Two candidate structures for the inhibitor, named granulatimide ( 4 ) and isogranulatimide ( 5 ), have been prepared via a short and efficient biomimetic synthesis involving the photolysis of didemnimide A ( 1 ). The synthesis revealed that the correct structure for the naturally occurring G2 checkpoint inhibitor is isogranulatimide ( 5 ). Granulatimide ( 4 ), the other candidate structure, was also found to be a G2 checkpoint inhibitor, and it was subsequently detected in chromatographic fractions associated with purification of D. granulatum alkaloids. Granulatimide ( 4 ) and isogranulatimide ( 5 ) represent the first examples of a new class of G2 specific cell cycle checkpoint inhibitors and the first ones identified through a rational screening program.",10.1021/jo981607p,1998-11-25,0.5868847187675943
Tetrahedron,A new method for the synthesis ofα-amino-β-lactams,,10.1016/s0040-4039(01)95287-6,1978-01-01,0.5868824644476919
Angewandte Chemie International Edition,Total Synthesis of (−)‐Amphidinolide E,"The unique structural features of the cytotoxic marine macrolide (−)-amphidinolide E make it an intriguing synthetic target. Its total synthesis has now been completed by employing a radical cyclization of a β-alkoxy acrylate to form the oxolane ring, a Kocienski–Julia olefination to create the E CC bond, and a lactonization reaction to close the macrocyclic ring.",10.1002/anie.200603363,2006-11-09,0.5868784991647074
Journal of Organic Chemistry,Construction of the Tetracyclic Skeleton of Polycyclic Norcembranoids Sinudenoids B–D Via Ireland-Claisen Rearrangement,"Sinudenoids B-D represent a biologically significant and structurally intricate family of natural products distinguished by their unique [5-5-6-6] tetracyclic skeleton. Herein, we present an efficient strategy for the asymmetric synthesis of their [5-5-6-6] tetracyclic framework. Key features of our approach include a convergent synthetic strategy driven by esterification, a pivotal Ireland-Claisen rearrangement to construct a C11-C12 bond, followed by efficient lactonization and isomerization, and a ring-closing metathesis to complete the [5-5-6-6] tetracyclic skeleton.",10.1021/acs.joc.5c00317,2025-03-20,0.5868702214705258
Tetrahedron,Synthesis of a key intermediate for Thienamycin and Imipenem through stereoselective two-direction elongation of asymmetrized bis(hydroxymethyl)acetaldehyde (BHYMA∗),,10.1016/0040-4039(95)02177-9,1996-01-01,0.586870103400798
Organic Letters,"Efficient One-Pot Synthesis of Polyfunctionalized Thiophenes via an Amine-Mediated Ring Opening of EWG-Activated 2-Methylene-1,3-dithioles","An amine-mediated ring-opening reaction of EWG-activated 2-methylene-1,3-dithioles (EWG = electron-withdrawing group) was disclosed, and a new route to highly substituted thiophenes was developed via the ring opening of 1,3-dithioles and subsequent intramolecular annulation and amine substitution. This one-pot reaction could proceed efficiently under mild conditions.",10.1021/ol7021752,2007-10-11,0.586865098890568
Tetrahedron,Synthesis of bis(pyrrol-2-yl)arenes by Pd-catalyzed cross coupling,,10.1016/j.tetlet.2006.08.098,2006-09-15,0.5868641895288509
Journal of Organic Chemistry,"The Synthesis of Homoallylic Amines Utilizing a Cuprate-Based 1,2-Metalate Rearrangement","Lithiation of the N-2,4,6-triisopropylbenzenesulfonyl-2-pyrroline (16) and treatment of the resulting cyclic vinyllithium reagent with R2CuCNLi2 produced an acyclic vinyl organometallic species that, when treated with an electrophile (H2O or RX), gave the homoallylic sulfonamides 18a-k in 37-93% yields and in > 95% diastereoselectivity. The deprotection of a representative homoallylic sulfonamide 18d was achieved in 83% yield by sonication in the presence of lithium wire and catalytic 4,4'-di-tert-butylbiphenyl (DBB). The efficacy of this general procedure for the production of homoallylic amine derivatives is demonstrated by the preparation of the diene amine 25, a key intermediate in the synthesis of a squalene synthetase inhibitor.",10.1021/jo001386z,2000-12-28,0.5868639679226738
Tetrahedron,New strategy for this construction of carbapenems. Total synthesis of 6-epi PS-5 and PS-5.,,10.1016/s0040-4039(00)94734-8,1990-01-01,0.5868559796088864
Organic Letters,Synthesis of Tri-<i>O</i>-acetyl-<scp>d</scp>-allal from Levoglucosenone,"Tri-O-acetyl-D-allal has been enantiospecifically synthesized in six steps from levoglucosenone in 55% overall yield. A key step in the synthesis is the anhydro bridge ring-opening with concomitant formation of a 1,3-oxathiolane-2-thione ring.",10.1021/ol302061a,2012-08-24,0.5868509303767133
Journal of the American Chemical Society,"Total Syntheses of Scaparvins B, C, and D Enabled by a Key C–H Functionalization","The clerodane diterpene family possesses an impressive range of bioactivities and high synthetic challenge due to their unique amalgamation of rings, stereocenters, and oxygenation. Herein, we disclose the first total syntheses of three members, scaparvins B, C, and D, through a route fueled by several chemoselective and carefully orchestrated steps. One such operation is a tailored late-stage C-H functionalization converting a carboxylic acid into a lactone through the oxidation of a tertiary C-H bond under conditions that minimize epoxidation of an alkene. This step, among others, afforded critical functionality to complete the targets. In addition, use of an appropriate chiral catalyst with a Rawal diene renders the sequence enantioselective.",10.1021/jacs.7b06185,2017-12-11,0.5868509141433275
Tetrahedron,An enantio- and stereocontrolled route to epopromycin B via cinchona alkaloid-catalyzed Baylis–Hillman reaction,,10.1016/s0040-4039(01)01676-8,2001-10-01,0.5868448779694032
Tetrahedron,"Synthesis and properties of 9,10-diphenylbicyclo[6.2.O]decapentaenes. A new synthesis of the novel conjugated system from a valence isomer",,10.1016/s0040-4039(01)83522-x,1977-01-01,0.5868425738395964
Journal of Organic Chemistry,Total Synthesis of (±)-Deoxypenostatin A. Approaches to the Syntheses of Penostatins A and B,"A short synthesis of (+/-)-deoxypenostatin A (28) has been carried out using the convergent coupling of dienal 11, epoxide 13, and methylenetriphenylphosphorane (17) to prepare trienol 19 in only two steps. The key step is the Yb(OTf)(3)-catalyzed intramolecular Diels-Alder reaction of hydrated trienyl glyoxylate 23, which gives lactone 24 stereoselectively. Elaboration of lactone 24 to enone 27 by an intramolecular Horner-Emmons Wittig reaction and epimerization completes the synthesis of 28. Modest yields of Diels-Alder adducts 45a and 46a could be prepared analogously from MEM ether 44c, but the sensitivity of several of the intermediates precluded the elaboration of 45a to penostatin A (1).",10.1021/jo000850x,2000-11-17,0.5868362394005383
Synlett,Ligand-Mediated Enantioselective Synthesis of Acyclic Pyrrole Carbinols,"The enantioselective synthesis of acyclic pyrrole carbinols via ligand-mediated addition of lithium pyrrolate to aldehydes, and subsequent exploitation of the resulting stereocentre as a stereodirecting group in syn- or anti-selective 1,3-reductions of ketone functionality in the parent aldehyde is described. © Georg Thieme Verlag Stuttgart.",10.1055/s-2005-872698,2005-01-01,0.5868341052616847
Synlett,A Simple Synthesis of Phosphonoformamides,All articles of this category A novel route to C-amides of the antiviral drug Foscarnet via the PFA diester 4 is described. The reaction with amines is facilitated by in situ intramolecular cyclization to form a more reactive intermediate. Foscarnet - prodrug - phosphonate - peptidomimetic,10.1055/s-1998-1975,1998-12-01,0.5868288995494901
Organic Letters,Novel Synthesis of the ABC Rings of Solanoeclepin A,"A stereocontrolled synthesis of the ABC rings of solanoeclepin A has been achieved. The seven-membered ring B was synthesized by an intramolecular Prins-ene reaction between an aldehyde and an enyne-dicobalthexacarbonyl complex. The acetylene in this synthesis plays multiple roles: to join the A and C rings, to allow stereoselective cyclization via dicobalthexacarbonyl complexation, and to facilitate Nicholas cation stabilization followed by deprotonation to form an endo-cyclic olefin (Nicholas-Prins cyclization).",10.1021/ol5029755,2014-11-06,0.5868205892355579
Tetrahedron,The first total synthesis of the core class II disialylated hexasaccharide as a building block for glycopeptide synthesis,,10.1016/s0040-4039(99)00605-x,1999-05-01,0.5868189490389139
Tetrahedron,Negishi coupling strategy of a repetitive two-step method for oligoarene synthesis,,10.1016/j.tetlet.2006.06.048,2006-07-13,0.5868168207283954
Synlett,Iodine-mediated Ring Closing Alkene Iodoamination with N-Debenzylation for the Asymmetric Synthesis of Polyhydroxylated Pyrrolidines,An iodine-mediated ring closing alkene iodoamination with N-debenzylation protocol provides a direct route for the asymmetric synthesis of polyhydroxylated pyrrolidines from homochiral β-amino acid derivatives.,10.1055/s-2004-820031,2004-01-01,0.5868135216798037
Tetrahedron,An efficient route to 4-aryloxycoumarins via one-pot reactions of 4-hydroxycoumarins with hypervalent iodine reagents,,10.1016/j.tetlet.2017.09.021,2017-09-14,0.5868069585228098
Journal of Organic Chemistry,"χ-Shaped Bis(areno)-1,4-dihydropyrrolo[3,2-<i>b</i>]pyrroles Generated by Oxidative Aromatic Coupling","A synthesis of dihydropyrrolo[3,2-b]pyrroles fused with two peripheral arenes or heterocyclic units has been realized through the concise route. These nearly planar compounds were prepared starting from assembling the central core via condensation of 2-aryl or 2-heteroarylbenzaldehydes with aromatic amines and diacetyl, followed by double intramolecular oxidative aromatic coupling. This two-step procedure afforded the desired products in overall yields of 5-36%, and it tolerates structural diversity of starting materials. All the final dyes exhibit strong blue fluorescence in solution.",10.1021/acs.joc.5b00052,2015-02-18,0.5868031726367758
Tetrahedron,A concise asymmetric total synthesis of (+)-fawcettimine,,10.1016/j.tetlet.2020.152329,2020-08-28,0.5868012253004155
Tetrahedron,A novel synthesis of K-13,,10.1016/0040-4039(94)85322-3,1994-10-01,0.586796207818376
Synlett,"A Short Synthesis of Methyl 3α,7α,12α-Triaminocholanoate, the ‘Triaza-Analogue’ of Methyl Cholate","Triamine 2a, a facial amphiphile and precursor for anion receptors, has been prepared in just four steps from the inexpensive steroid cholic acid.",10.1055/s-2005-865221,2005-04-14,0.5867947994707312
Tetrahedron,Asymmetric additions of 1-alkenylcopper reagents to chiral enoates: Enantioselective synthesis of california red scale pheromone.,,10.1016/s0040-4039(00)84198-2,1986-01-01,0.586786553643201
European Journal of Organic Chemistry,Synthesis of Enantiomerically Pure β‐Hydroxy Ketones via β‐Keto Weinreb Amides by a Condensation/Asymmetric‐Hydrogenation/Acylation Sequence,"An established route to enantiomerically pure β‐hydroxy ketones proceeds through the asymmetric hydrogenation of β‐keto esters, an ester/amide exchange, and the use of the resulting β‐hydroxy amide for the acylation of an organometallic compound. We shortened this route by showing that β‐keto Weinreb amides are hydrogenated with up to 99 % ee in the presence of [Me 2 NH 2 ] + {[RuCl( S )‐BINAP] 2 (µ‐Cl) 3 } – (0.5 mol‐%) at room temp./5 bar. These Weinreb amides were prepared by seemingly obvious yet unprecedented condensations of lithiated N ‐methoxy‐ N ‐methylacetamide with carboxylic chlorides (51–87 % yield). The resulting β‐hydroxy Weinreb amides were used for the acylation of organolithium and Grignard reagents. They thus gave enantiomerically pure β‐hydroxy ketones (28 examples). A selection of these compounds gave anti ‐1,3‐diols after another C=O bond hydrogenation, or syn ‐1,3‐diols by a Narasaka–Prasad reduction.",10.1002/ejoc.201601202,2016-10-20,0.586779717613218
Synlett,Copper(I)-Catalyzed Enantioselective Boryl Substitution of Allyl Acylals: An Efficient Approach for Enantioenriched α-Chiral γ-Acetoxyallylboronates,"A novel approach has been developed for the enantioselective synthesis of α-chiral γ-acetoxyallylboronates via the copper(I)-catalyzed γ-boryl substitution of allyl acylals. This reaction proceeded with high E / Z selectivity and enantioselectivity ( E / Z = >99:1, up to 80% yield, up to 99% ee). The subsequent allylation of aldehyde with the allylboronate afforded the monoprotected anti -1,2-diol derivative with high stereoselectivity.",10.1055/s-0036-1588354,2016-11-21,0.5867754302904046
Journal of the American Chemical Society,Total Synthesis of 2‘-<i>O</i>-Methylmyxalamide D and (6<i>E</i>)-2‘-<i>O</i>-Methylmyxalamide D,"Hetero-bis-metalated 1,3,5-hexatrienes are employed in the linchpin coupling of synthetic fragments for the convergent construction of the central pentaene of the antifungal agent 2‘- O -methylmyxalamide D and its (6 E ) isomer. Sequential Stille and Suzuki−Miyaura couplings interpolate the boron/tin triene into the pentaene chain. The total synthesis of O -methylmyxalamide D and its (6 E ) isomer was accomplished efficiently.",10.1021/ja070265e,2007-03-15,0.5867688613251417
Angewandte Chemie International Edition,Stereocontrolled Synthesis of Carbon Chains Bearing Contiguous Methyl Groups by Iterative Boronic Ester Homologations: Application to the Total Synthesis of (+)‐Faranal,Adding links to the chain: A quadruple homologation of a boronic ester converts a simple vinyl iodide into a complex precursor to faranal with very high levels of diastereo- and enantiocontrol. This enables the synthesis of (+)-faranal to be completed in just six steps and 18 % overall yield from propyne.,10.1002/anie.200901194,2009-05-13,0.5867684531969966
Synthesis,A Photochemical Strategy for the Synthesis of Caprolactams via Dearomative Ring Expansion of Nitroarenes,"Abstract This paper outlines a novel strategy for the preparation of seven-membered-ring lactams from simple nitroarenes. The approach is based on a photochemical dearomative ring expansion starting with the conversion of the nitro group into a singlet nitrene. This process is mediated by blue light, occurs at room temperature and overall enables the insertion of the nitro N-atom into the benzenoid framework. This step transforms the aromatic starting material into a seven-membered ring azepine that, following hydrogenation and hydrolysis, is converted into the desired caprolactams in just three steps.",10.1055/a-2288-6944,2024-03-15,0.5867668338031258
Angewandte Chemie International Edition,"Inside Back Cover: Short and Divergent Total Synthesis of (+)‐Machaeriol B, (+)‐Machaeriol D, (+)‐Δ<sup>8</sup>‐THC, and Analogues (Angew. Chem. Int. Ed. 29/2015)","Machaeriols and cannabinoids can be synthesized by a short and divergent approach featuring highly efficient stereoselective transformations from a common precursor, commercially available (S)-perillic acid. In their Communication on page 8547 ff., A. Studer and F. Klotter report the use of a stereospecific palladium-catalyzed decarboxylative γ-arylation and a one-pot sequence comprising a stereoselective hydroboration followed by oxidation or reduction as key steps.",10.1002/anie.201505496,2015-06-25,0.5867634530759209
Organic Letters,Concise Route to 3-Arylisoquinoline Skeleton by Lewis Acid Catalyzed C(sp<sup>3</sup>)–H Bond Functionalization and Its Application to Formal Synthesis of (±)-Tetrahydropalmatine,"An expeditious route to furnish an isoquinoline skeleton via hydride shift mediated C-H bond functionalization was developed. In this process, an unusual [1,5]-H shift without the assistance of the adjacent heteroatom took place to produce tetrahydroisoquinoline derivatives in good to excellent chemical yields. The formal synthesis of (±)-tetrahydropalmatine was achieved by exploiting this new transformation.",10.1021/ol300180w,2012-03-05,0.5867594779884147
Tetrahedron,Towards the Synthesis of Calyculin: A Synthetic Intermediate Corresponding to the C(26)-C(37) Fragment,,10.1016/0040-4039(92)88107-g,1992-04-01,0.5867528510545438
Synlett,"Synthesis of 1,2,3-Trisubstituted Pyrrolidines and 2,3-Disubstituted Tetrahydrofurans via Diastereoselective Reductive Cyclization of γ-Chloroimines and γ-Chloroketones","A new diastereoselective synthetic approach towards 1,2,3-trisubstituted pyrrolidines and 2,3-disubstituted tetrahydrofurans is described. The synthesis of the pyrrolidines involves reductive cyclization of gamma-chloroketimines, which were generated in situ from the reaction of 3-substituted 5-chloro-2-pentanones and a primary amine. Various reduction conditions were explored to induce a diastereoselective reductive cyclization. 2,3-Disubstituted tetrahydrofurans were obtained by the direct reduction of 3-substituted 5-chloro-2-pentanones with sodium borohydride.",10.1055/s-0031-1289544,2011-10-19,0.58674441604716
Tetrahedron,An efficient and stereospecific total synthesis of dl-protolichesterinic acid,,10.1016/s0040-4039(01)91616-8,1976-05-01,0.5867426483496607
Tetrahedron,"A short and efficient synthesis of furo[2,3-b]indoles",,10.1016/j.tetlet.2010.06.068,2010-06-20,0.5867416254323671
Tetrahedron,A short and efficient synthesis of unnatural (R)-nicotine,,10.1016/s0040-4039(00)01675-0,2000-11-01,0.5867416254323671
Tetrahedron,A short and efficient synthesis of phenolcar☐amides,,10.1016/s0040-4039(00)81595-6,1983-01-01,0.5867416254323671
Tetrahedron,A short and efficient synthesis of (±)-β-cuparenone,,10.1016/j.tetlet.2006.03.012,2006-03-25,0.5867416254323671
Tetrahedron,Short and efficient synthesis of the antitumor heptenes melodienone and isomelodienone,,10.1016/s0040-4039(98)01471-3,1998-09-01,0.5867416254323671
Tetrahedron,"A short, efficient synthesis of (±)valerane",,10.1016/s0040-4039(00)95789-7,1987-01-01,0.5867416254323671
Tetrahedron,A short and efficient synthesis of 2′-deoxybenzo- and pyridoimidazole C-nucleosides,,10.1016/s0040-4039(03)01401-1,2003-07-01,0.5867416254323671
Synthesis,"A Short and Efficient Synthesis of 3,6-Anhydro-hexosides",,10.1055/s-1983-30371,1983-01-01,0.5867416254323671
Tetrahedron,A short and efficient synthesis of (+)-calystegine B 2,,10.1016/s0040-4039(00)02262-0,2001-02-01,0.5867416254323671
Tetrahedron,A short and efficient synthesis of 1-deoxy-castanospermine and 1-deoxy-8a-epi-castanospermine,,10.1016/s0040-4039(00)02103-1,2001-01-01,0.5867416254323671
Tetrahedron,A short and efficient synthesis of renealtins A and B,,10.1016/j.tetlet.2007.09.025,2007-09-11,0.5867416254323671
Tetrahedron,A very short and efficient synthesis of (+)-conocephalenol,,10.1016/s0040-4039(97)10391-4,1997-12-01,0.5867416254323671
Tetrahedron,A Short and Efficient Synthesis of (±) Laevigatin,,10.1016/s0040-4039(97)01812-1,1997-10-01,0.5867416254323671
Journal of Organic Chemistry,"Coupling of Bulky, Electron-Deficient Partners in Aryl Amination in the Preparation of Tridentate Bis(oxazoline) Ligands for Asymmetric Catalysis","A new class of tridentate bis(oxazoline) ligands 7, in which an N-phenylaniline unit links the two oxazoline rings, has been prepared. The key step in their synthesis is a Hartwig-Buchwald type Pd-catalyzed aryl amination between the two bulky o-substituted coupling partners, 2-(2'-bromophenyl)oxazolines 8 and 2-(o-aminophenyl)oxazolines 9. By varying the substituent on the coupling partners, a range of 10 ligands has been prepared in good yield. During the synthesis of 2-(o-aminophenyl)oxazolines 9a-d, a number of products of unexpected side reactions were isolated in two of the three steps. Alternatively, the required 2-(o-aminophenyl)oxazolines 9 were obtained by a DAST-promoted cyclodehydration of hydroxyamides 12a-d without formation of any byproducts.",10.1021/jo0262558,2002-11-01,0.5867388580443508
Tetrahedron,Selective derivatization of d-galactose towards a practical synthesis of C-6 l-fucose analogues,,10.1016/j.tetlet.2012.08.127,2012-09-13,0.5867378627304513
Organic Letters,Synthesis of the C20–C32 Tetrahydropyran Core of the Phorboxazoles and the C22 Epimer via a Stereodivergent Michael Reaction,"A stereoselective synthesis of the C20-C32 tetrahydropyran core of the phorboxazoles has been achieved in only seven steps and in a 31% overall yield. The C22 epimer was also synthesized. The key step was a silyl ether deprotection/oxy-Michael cyclization. When this step was conducted under Brønsted acid conditions, the C20-C32 core was formed with the desired 2,6-cis-stereochemistry. However, when the silyl ether deprotection/oxy-Michael cyclization was conducted under fluoride conditions buffered with acetic acid, the C22 epimer of the core was the sole product.",10.1021/ol3026523,2012-10-22,0.586737624153527
Synthesis,An Expeditious Enantioselective Synthesis of Methyl <i>trans</i>-Chrysanthemate,"Methyl trans-chrysanthemate has been prepared in few steps from isopropylidenediphenylsulfurane and methyl (E)-3-(3, 3-dimethyloxiran-2-yl)prop-2-enoate. The latter was obtained from methyl 4-oxobutenoate or 3-methylbut-2-en-1-ol. The Sharpless catalytic epoxidation reaction allows an asymmetric version of this transformation.",10.1055/s-2002-34388,2002-09-26,0.586733739669742
Organic Letters,"Total Syntheses of Nannocystins A and A0, Two Elongation Factor 1 Inhibitors","Asymmetric total syntheses of nannocystins A and A0 were achieved in a convergent route starting from simple materials. Nannocystin family natural products bear potent anticancer activity as elongation factor 1 inhibitors. In this synthesis, the challenging tertiary amide bond was constructed by peptide coupling between an acyl chloride and a secondary amine. A late-stage ring-closing metathesis reaction successfully rendered the macrocycle. This efficient synthetic strategy should be applicable to other nannocystins and analogues and therefore should benefit future structure-activity relationship studies.",10.1021/acs.orglett.6b02352,2016-09-06,0.5867237422948373
Journal of Organic Chemistry,Total Synthesis of Spiromamakone A and Structure Revision of Spiropreussione A,"Spiromamakone A is a racemic natural product having a naphthyl acetal group on a spiro[4,4]nonadiene skeleton. Its total synthesis was achieved by double oxa-Michael addition of 1,8-dihydroxynaphthalene to 2-(1-bromoalkylidene)-4-isopropoxy-4-cyclopentene-1,3-dione, which was prepared by palladium(II)-catalyzed ring expansion of 4-(1-alkynyl)-4-hydroxy-3-isopropoxy-2-cyclobuten-1-one, and a subsequent intramolecular aldol reaction. The synthesis using optically active intermediates enabled identification of the racemization step of spiromamakone A and revealed that spiromamakone A and spiropreussione A are identical; the latter had been reported as a constitutional isomer of the other.",10.1021/acs.joc.8b01075,2018-06-13,0.5867225722050239
Journal of Organic Chemistry,Expeditious Construction of the DEF Ring System of Thiersinine B,"Construction of a DEF ring model of thiersinine B has been achieved from a Wieland-Miescher ketone derivative by a five-step sequence featuring a one-pot regioselective α-allylation of the starting α,β-unsaturated ketone via the Claisen rearrangement and a double dihydroxylation of a dienone intermediate.",10.1021/jo101258f,2010-08-18,0.5867207711940826
Journal of the American Chemical Society,A Concise Synthesis of (+)-Artemisinin,"Malaria represents one of the most medically and economically debilitating diseases present in the world today. Fortunately, there exists a highly effective treatment based on the natural product artemisinin. Despite the development of several synthetic approaches to the natural product, a streamlined synthesis that utilizes low-cost chemical inputs has yet to materialize. Here we report an efficient, cost-effective approach to artemisinin. Key to the success of the strategy was the development of mild, complexity-building reaction cascades that allowed the use of readily available, affordable cyclohexenone as the key starting material.",10.1021/ja3061479,2012-08-06,0.5867182589592724
Tetrahedron,Novel palladium-catalyzed oxazolidone synthesis,,10.1016/s0040-4039(00)00924-2,2000-08-01,0.5867106487425492
Journal of the American Chemical Society,Concise Total Synthesis of Salimabromide,"We achieved a concise total synthesis of salimabromide by using a novel intramolecular radical cyclization to simultaneously construct the unique benzo-fused [4.3.1] carbon skeleton and the vicinal quaternary stereocenters. Other notable transformations include a tandem Michael/Mukaiyama aldol reaction to introduce most of the molecule's structural elements, along with hidden information for late-stage transformations, an intriguing tandem oxidative cyclization of a diene to form the bridged butyrolactone and enone moieties spontaneously, and a highly enantioselective hydrogenation of a cycloheptenone derivative (97% ee) that paved the way for the asymmetric synthesis of salimabromide.",10.1021/jacs.2c08337,2022-10-04,0.5867088372129668
Chemical Science,Submonomer synthesis of peptoids containing <i>trans</i> -inducing <i>N</i> -imino- and <i>N</i> -alkylamino-glycines,"The use of hydrazones as a new type of submonomer in peptoid synthesis is described, giving access to peptoid monomers that are structure-inducing.",10.1039/d1sc00717c,2021-01-01,0.5867085622362238
Organic Process Research & Development,"Kilogram-Scale Preparation of the Amino Alcohol Fragment of Selgantolimod by Enzymatic Resolution of an α,α-Disubstituted Amino Ester","The chiral amino alcohol ( R )-2-amino-2-methylhexan-1-ol ( 1 ) is a key fragment in the synthesis of selgantolimod, a TLR8 agonist that is being evaluated for the treatment of hepatitis B infection. This report describes the development of a robust and scalable synthesis of the targeted amino alcohol featuring a hydrolase-catalyzed kinetic resolution of an α,α-disubstituted amino ester. The results highlight considerations for substrate design for the enzymatic resolution, the impact of pH on the resolution of an unprotected α,α-disubstituted amino ester derivative, and implementation of this substrate within a route to the desired amino alcohol fragment.",10.1021/acs.oprd.3c00271,2023-11-02,0.5867039393947135
Organic Process Research & Development,Safe and Practical Large-Scale Synthesis of 2-Aminoquinoline-6-Carboxylic Acid Benzyl Ester,"An efficient three-step sequence has been developed for the synthesis of 2-aminoquinoline-6-carboxylic acid benzyl ester starting from commercially available 6-quinolinecarboxylic acid. The process features a novel and exceptionally mild conversion of a quinoline N -oxide to a 2-aminoquinoline using a triethylamine/ammonium chloride buffered system. The development of this procedure is especially important since gaseous ammonia, ammonium hydroxide, and solutions of ammonia in alcohols all failed to deliver a safe and reliable process.",10.1021/op060044d,2006-04-05,0.5866933990963122
Journal of Organic Chemistry,"One-Pot Synthesis of 2-<i>R</i>-Naphtho[2,3-<i>b</i>]thiophene-4,9-diones via Cyclization of 2-(<i>R</i>-Ethynyl)-1,4-naphthoquinones with Na<sub>2</sub>S<sub>2</sub>O<sub>3</sub>","The concise and efficient one-pot synthesis of 2- R -naphtho[2,3- b ]thiophene-4,9-diones from 2-bromo-1,4-naphthoquinone and alkynes has been developed. The reaction proceeds through the formation of 2-( R -ethynyl)-1,4-naphthoquinones, which undergo transformation with Na 2 S 2 O 3 to 2- R -naphtho[2,3- b ]thiophene-4,9-diones via C–H sulfuration, accompanied by the formation of the aromatic Bunte salt, followed by its air oxidation and 5-endo-dig cyclization. The protocol is characterized by simplicity, good tolerance for functional groups, relatively mild conditions, and commercially available starting compounds.",10.1021/acs.joc.1c00852,2021-08-04,0.5866876023361409
Angewandte Chemie International Edition,A Mixed‐Ligand Chiral Rhodium(II) Catalyst Enables the Enantioselective Total Synthesis of Piperarborenine B,"A novel, mixed-ligand chiral rhodium(II) catalyst, Rh2(S-NTTL)3(dCPA), has enabled the first enantioselective total synthesis of the natural product piperarborenine B. A crystal structure of Rh2(S-NTTL)3(dCPA) reveals a ""chiral crown"" conformation with a bulky dicyclohexylphenyl acetate ligand and three N-naphthalimido groups oriented on the same face of the catalyst. The natural product was prepared on large scale using rhodium-catalyzed bicyclobutanation/ copper-catalyzed homoconjugate addition chemistry in the key step. The route proceeds in ten steps with an 8% overall yield and 92% ee.",10.1002/anie.201600766,2016-03-16,0.5866838360165514
Tetrahedron,"Synthesis of the mannosidase inhibitors swainsonine and 1,4-dideoxy-1,4-imino-D-mannitol and of the ring contracted swainsonines, (1S, 2R, 7R, 7aR)-1,2,7-trihydroxypyrrolizidine and (1S, 2R, 7S, 7aR)-1,2,7-trihydroxypyrrolizidine",,10.1016/s0040-4039(01)93953-x,1989-01-01,0.5866794414460488
Organic Letters,A Concise Formal Total Synthesis of TMC-95A/B Proteasome Inhibitors,[reaction: see text] A formal total synthesis of proteasome inhibitors TMC-95A/B is described. The synthesis features a stereoselective modified Julia olefination and a diastereoselective dihydroxylation to construct the highly oxidized tryptophan residue.,10.1021/ol0272545,2002-12-21,0.5866640993131831
Journal of Organic Chemistry,"Bioinspired Diastereoconvergent Synthesis of the Tricyclic Core of Palodesangrens via Diels–Alder Reaction, LiAlH<sub>4</sub>-Mediated Isomerization, and Acid-Mediated Cyclization","The cyclohexene moiety of the tricyclic 6,7-diaryl-tetrahydro-6 H -benzo[ c ]chromene core of palodesangrens could be assembled in a biomimetic and step-economical fashion by the Diels–Alder reaction between the electron-rich ( E )-1,3-butadienylarenes as the diene and the electron-deficient chalcones as the dienophile. During the reduction of ketone to the corresponding alcohol by LiAlH 4, the mixture of endo and exo isomers underwent a novel diastereoconvergent LiAlH 4 -mediated isomerization to install the desired stereochemistry at C10a. Subsequent pyran ring closure under acidic conditions installed the stereochemistry at the remaining C6. Overall, the tricyclic core of palodesangrens could be prepared in three steps and up to 38% yield.",10.1021/acs.joc.8b00668,2018-04-16,0.5866618217897235
European Journal of Organic Chemistry,Synthesis of New Allocolchicinoids with Seven‐ and Eight‐Membered B‐Rings by Enyne Ring‐Closing Metathesis,"Abstract Total syntheses of allocolchicines 4 and 5 , with the ester functionality in the C‐ring at the C10 or C11 positions, is reported. An asymmetric synthesis of (7 S )‐allocolchicine 5 is also described. The main features included the elaboration of a common intermediate, the AB bicyclic ring system, in which the construction of the seven‐membered ring was achieved by an enyne ring‐closing metathesis (RCM) reaction. A subsequent Diels–Alder/aromatization sequence afforded the set of functionalized ring‐C allocolchicinoids with high regioselectivity. This strategy was also applied for the synthesis of allocolchicine 6 , containing an eight‐membered B‐ring.(© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2008)",10.1002/ejoc.200800595,2008-09-05,0.586660499159068
Tetrahedron,"Novel and stereoselective asymmetric synthesis of an amino sugar analogue, furanodictine A",,10.1016/j.tetlet.2003.12.135,2004-01-17,0.5866582831470546
Organic Letters,Synthetic Progress toward Azadirachtins. 2. Enantio- and Diastereoselective Synthesis of the Right-Wing Fragment of 11-<i>epi</i>-Azadirachtin I,"A stereoselective three-component coupling reaction of allylzinc bromide, silyl glyoxylate, and a β-lactone has been developed. This has been successfully applied to the enantio- and diastereoselective synthesis of the fully functionalized furopyran moiety of azadirachtins.",10.1021/acs.orglett.5b00831,2015-04-28,0.5866563333985249
Organic Letters,First Synthesis of the Three Isomeric Parent Disilacyclohexanes. An Improved Preparation of Methylene Di-Grignard,"Ring closure of 1,5-dibromo-1,5-disilapentane with methylene di-Grignard was the key step in the preparation of the parent 1,3-disilacyclohexane. For that purpose, the preparation of methylene di-Grignard has been improved and simplified. The successful synthesis of the isomeric 1,2- and 1,4-disilacyclohexanes is also reported.",10.1021/ol900462z,2009-04-02,0.5866545805700426
Organic Letters,Stereocontrolled Syntheses of Epimeric 3-Aryl-6-phenyl-1-oxa-7-azaspiro[4.5]decane NK-1 Receptor Antagonist Precursors,"[structure: see text]. Complementary stereoselective syntheses of individual C3 epimers of the NK-1 receptor antagonist precursor 1 have been developed. Both diastereomers were derived from the common intermediate 3; introduction of the 3S stereocenter in 1a was achieved through hydrogenation of an arylated dihydrofuran, whereas the corresponding stereogenic center in 1b was installed using a stereo- and regioselective alkene hydroarylation.",10.1021/ol006944a,2001-02-16,0.5866503433068319
Organic Letters,A One-Pot Synthesis of Dibenzofurans from 6-Diazo-2-cyclohexenones,A novel and efficient protocol for the rapid construction of dibenzofuran motifs from 6-diazo-2-cyclohexenone and ortho-haloiodobenzene has been developed. The process involves one-pot Pd-catalyzed cross-coupling/aromatization and Cu-catalyzed Ullmann coupling.,10.1021/acs.orglett.5b02783,2015-11-24,0.5866501273258995
Tetrahedron,A novel method for the synthesis of a C/D-ring synthon of vitamin D derivatives from hyodeoxycholic acid,,10.1016/s0040-4039(98)80038-5,1999-01-01,0.5866469071814556
Tetrahedron,Towards the synthesis of epothilone A: Enantioselective preparation of the thiazole sidechain and macrocyclic ring closure,A synthetic approach to a new class of microtubule-stabilizing natural products is described which employs a macrocyclic olefination strategy to cyclize the 16-membered lactone ring. The C13C19 thiazole subunit of epothilone A and B is prepared in high enantioselectivity using a catalytic asymmetric allylation reaction.,10.1016/s0040-4039(97)00285-2,1997-03-01,0.5866442757395498
Organic Letters,Modular Synthesis of Naphthothiophenes by Pd-Catalyzed Tandem Direct Arylation/Suzuki Coupling,A short and highly modular three-step synthesis of a new class of substituted naphthothiophenes has been developed exploiting a Pd-catalyzed tandem direct arylation/Suzuki coupling transformation as the key step.,10.1021/ol201585a,2011-07-27,0.5866406167654424
Synthesis,Synthesis and Intramolecular Cyclisation of 5-Aminoimidazolealkanoates and Their Conversion to Purine Derivatives,"All articles of this category Synthesis of ethyl (9-hypoxanthinyl)- and (9-adeninyl)acetates, ethyl 3-(9-hypoxanthinyl)- and 3-(9-adeninyl)propanoates, and ethyl 2-(9-hypoxanthinyl)- and 2-(9-adeninyl)propanoates from appropriately substituted 5-aminoimidazole precursors is described. Cyclisation of the imidazoles also resulted in formation of an imidazopyrimidine and novel imidazoimidazoles.",10.1055/s-1991-26403,1991-01-01,0.5866310963986491
Tetrahedron,Chemical design and synthesis of unsymmetrical diamino proligands employing a flexible route,,10.1016/j.tetlet.2012.08.057,2012-08-19,0.5866307865244607
Journal of the American Chemical Society,A Concise Synthesis of the Fully Functional Lactide Core of Cycloviracin B with Implications for the Structural Assignment of Related Glycolipids,"The absolute stereochemistry at the site of attachment of the fatty acid residues to the lactide core of the glycolipids cycloviracin B1 (1) and glucolipsin A (13) has been elucidated as (3R,3'R) by comparison of their 13C NMR data with those of the three possible, differently configured core structures 9, 12, and 14. Moreover, a careful analysis of this set of NMR data allows us to conclude that the structures previously proposed for a seemingly closely related class of antivirally active compounds, i.e., the fattiviracin family, need revision. The key step en route to the symmetrical dilactones 9 and 12 consists of a highly efficient cyclodimerization process which exploits the template effect exerted by potassium cations on the hydroxy acid cyclization precursor. The latter is obtained in excellent overall yield by a sequence involving ring-opening Claisen condensation of pentadecanolide to form the functionalized beta-ketoester 4, asymmetric hydrogenation catalyzed by [(BINAP)RuCl2]2.NEt3, and a beta-selective glycosylation reaction using trichloroacetimidate 6. The unsymmetrical dilactone 14, in contrast, is prepared by a stepwise approach based on a Yamaguchi lactonization as the means to close the macrocyclic ring.",10.1021/ja0175791,2002-01-25,0.5866303593703792
Organic Letters,Consecutive Cycloaddition/S<sub>N</sub>Ar/Reduction/Cyclization/Oxidation Sequences: A Copper-Catalyzed Multicomponent Synthesis of Fused N-Heterocycles,"A highly efficient multicomponent domino protocol has been developed for the synthesis of 5-phenyl-[1,2,3]triazolo[1,5-c]quinazolines from simple and readily available (E)-1-bromo-2-(2-nitrovinyl)benzenes, aldehydes, and sodium azide. This elegant domino process involved consecutive [3 + 2] cycloaddition, copper-catalyzed S(N)Ar, reduction, cyclization, and oxidation sequences. Notably, sodium azide acted as a dual nitrogen source in the construction of this novel fused N-heterocycle.",10.1021/acs.orglett.5b01242,2015-05-21,0.5866237923489717
Tetrahedron,"Enantioselective synthesis of the methylenecyclopropane derivative related to hypoglycine, starting from malic acid",,10.1016/s0040-4039(00)79488-3,1991-01-01,0.5866196054185538
Journal of Organic Chemistry,Total Synthesis of the Annonaceous Acetogenin (+)-Asimicin. Development of a New Bidirectional Strategy,"The total synthesis of the Annonaceous acetogenin (+)-asimicin is described. The approach employs the ( R )-α-OSEM allylic stannane 7 of >95% ee and the dialdehyde 8 obtained from ( S,S )-diethyl tartrate. Addition of 7 to 8 in the presence of InCl 3 afforded the bis-adduct 9 in 71% yield. Tosylation and treatment with TBAF led to the core bis-tetrahydrofuran intermediate, diol 11, in 78% yield. Mono tosylation ( n -BuLi, TsCl, THF−DMSO) and subsequent hydrogenolysis with LiBEt 3 H gave alcohol 14 . The iodide 15 was coupled with the higher-order vinylcyanocuprate to afford olefin 30 . This was converted to diol 31 of high ee by the Sharpless protocol. This diol yielded the epoxide 33 via the mono-trisylate 32 . Addition of ( R )-lithio-2-(OTBS)-3-butyne in the presence of BF 3 ·OEt 2 afforded the alcohol 34 . The SEM derivative 35 was treated with TBAF, and the resulting alcohol was converted to the butenolide 38 by a sequence involving treatment with (CF 3 CO) 2 O, then Pd(PPh 3 ) 4, CO, THF−H 2 O, and finally AgNO 3 /silica gel. Cleavage of the SEM protecting group with PPTS in ethanol afforded (+)-asimicin ( 39 ).",10.1021/jo970423s,1997-08-01,0.5866108816331186
Synlett,Diastereoselective Synthesis of (±)-Ambrox by Titanium(III)-Catalyzed Radical Tandem Cyclization,"A synthesis of (±)-ambrox, a compound with delicious ambergris-type scent, is presented. The key step is a highly diastereoselective titanocene(III)-catalyzed radical tandem cyclization of a farnesol derivative.",10.1055/s-0035-1560594,2015-12-09,0.5866106413337501
Journal of Organic Chemistry,Substrate-Controlled and Organocatalytic Asymmetric Synthesis of Carbocyclic Amino Acid Dipeptide Mimetics,The asymmetric synthesis of a carbocyclic delta-amino acid representing the P(2)/P(3) subunit of a nonpeptidic truncated peptidomimetic molecule is described relying on two independent approaches.,10.1021/jo100017t,2010-04-14,0.5866096581797349
Journal of the American Chemical Society,Total Synthesis of Aleutianamine,"High Resolution Image Download MS PowerPoint Slide Aleutianamine is a recently isolated pyrroloiminoquinone natural product that displays potent and selective biological activity toward human pancreatic cancer cells with an IC 50 of 25 nM against PANC-1, making it a potential candidate for therapeutic development. We report a synthetic approach to aleutianamine wherein the unique [3.3.1] ring system and tertiary sulfide of this alkaloid were constructed via a novel palladium-catalyzed dearomative thiophene functionalization. Other highlights of the synthesis include a palladium-catalyzed decarboxylative pinacol-type rearrangement of an allylic carbonate to install a ketone and a late-stage oxidative amination. This concise and convergent strategy will enable access to analogues of aleutianamine and further investigation of the biological activity of this unique natural product.",10.1021/jacs.3c10212,2023-11-15,0.5866088280197768
Tetrahedron,"Total synthesis of thromboxane B2 starting from (R,R)-tartaric acid as a chiral pool",,10.1016/s0040-4039(97)82953-x,1996-12-01,0.5866081212777321
Journal of Organic Chemistry,"BF<sub>3</sub>-Induced Rearrangement of Aziridino Cyclopropanes Derived from 2-Phenylsulfonyl 1,3-Dienes. Application to the Total Synthesis of (±)-Ferruginine","Total synthesis of the alkaloid (+/-)-ferruginine (1) has been developed via the 2-phenylsulfonyl 1,3-diene approach. BF(3)-induced rearrangement of the N-protected cyclohexane aziridino cyclopropane 8, derived from its corresponding epoxy cyclopropane, afforded the desired tropane alkaloid skeleton 9 in good yield. Michael addition of nitroethane (as an acyl anion equivalent) and transformation of the nitro group of the adduct 10 to a keto function gave 11. Elimination of benzenesulfinic acid and subsequent replacement of the tosyl group by a methyl group afforded the title compound 1.",10.1021/jo001147b,2000-11-14,0.5866057061517973
Journal of Organic Chemistry,Construction of the Fused Pentacycle of Talatisamine via a Combination of Radical and Cationic Cyclizations,"The fused 6/7/5/6/6-membered (ABCDE) ring system of talatisamine was synthesized in 22 steps. After preparation of the AE-ring structure from 2-(ethoxycarbonyl)cyclohexanone, elaboration of the carboskeleton was realized by sequential additions of allyl magnesium bromide and the lithiated C-ring. The C11-bridgehead radical derived from the ACE-ring underwent the 7-endo cyclization with the enone moiety to form the B-ring in C10-stereoselective and C11-stereospecific manners. The 6-endo cyclization of the remaining D-ring was in turn attained by using the silyl enol ether as the nucleophile and the PhSeCl-activated olefin as the electrophile. These radical and cationic cyclizations were demonstrated to be highly chemoselective, and they significantly contributed to streamlining the route to the intricately fused pentacycle of talatisamine.",10.1021/acs.joc.6b01011,2016-06-06,0.5865987348298894
Angewandte Chemie International Edition,Enantioselective Total Synthesis of (+)‐Incargranine A Enabled by Bifunctional Iminophosphorane and Iridium Catalysis,"Herein we report the first enantioselective total synthesis of (+)-incargranine A, in nine steps. The total synthesis was enabled by an enantioselective intramolecular organocatalysed desymmetrising Michael addition of a malonamate ester to a linked dienone substrate that established pivotal stereocentres with excellent enantio- and complete diastereoselectivity. Furthermore, a key hemiaminal intermediate was accessed by developing an iridium-catalysed reductive cyclisation, and the scope of this transformation was explored to produce a range of bicyclic hemiaminal motifs. Once installed, the hemiaminal motif was used to initiate a biomimetic cascade to access the natural product directly in a single step.",10.1002/anie.202314308,2023-11-13,0.5865980212559113
Organic Letters,A Novel Method for the Preparation of 4-Arylimidazolones,"A series of 4-arylimidazolones have been accessed via late-stage, palladium-mediated arylation of acetone- and cyclohexanone-derived 4-chloroimidazolones. The 4-chloroimidazolones were prepared via a novel rearrangement of the corresponding imidazolone N-oxides. This communication serves as an expansion of chemistry originally developed for our glucagon receptor antagonist program.",10.1021/ol401165e,2013-05-28,0.5865954189937115
Chemical Science,Catalytic asymmetric synthesis of cyclic amino acids and alkaloid derivatives: application to (+)-dihydropinidine and Selfotel synthesis,An asymmetric synthesis of cyclic amino acids having piperidine and azepane core structures was realized starting from readily available glycine and alanine esters by combination of phase-transfer catalyzed asymmetric alkylation and subsequent reductive amination. Some of these key intermediates were successfully transformed to natural alkaloid dihydropinidine and N-methyl-D-aspartate (NMDA) antagonist Selfotel.,10.1039/c0sc00250j,2010-01-01,0.5865890202652394
Journal of Organic Chemistry,Diastereoselective Total Synthesis of (+)-13-Stemarene by Fourth Generation Methods: A Formal Total Synthesis of (+)-18-Deoxystemarin,"The problem of constructing diastereoselectively the C/D ring system of stemarane diterpenes from a bicyclo[2.2.2]octane intermediate was solved resulting in very simple synthesis of (+)-13-stemarene 1. The obtaining of the latter represents also a formal synthesis of (+)-18-deoxystemarin 2. In the key step, the epimeric mixture 10, dissolved in toluene, was converted by the action of TsOH into (+)-stemar-13-en-15-one 28.",10.1021/jo200945s,2011-07-04,0.5865884679728891
Angewandte Chemie International Edition,Divergent Asymmetric Synthesis of Bonnadiene and <i>ent</i> ‐Polytrichastrene B,"Abstract We report herein the first asymmetric total synthesis of bonnadiene and ent ‐polytrichastrene B, two diterpenoids that share a common spirotricyclic skeleton. Notably, ent ‐polytrichastrene B also features a highly strained, sterically congested tetrasubstituted cyclopropane moiety, presenting significant synthetic challenges in both its construction and stereochemical control. The synthesis features: (1) palladium‐catalyzed enantioselective redox‐relay Heck alkenylation between electron‐withdrawing alkenyl triflate and primary alkenol to form the stereocenter at C7; (2) diastereoselective intramolecular [5+2] cycloaddition to rapidly assemble the unique [6,7,5] spirotricyclic skeleton; (3) sequential installation of the requisite alkyl groups and alkenes present in the targeted molecule by leveraging the functionalities positioned on the tricycle; (4) Fe‐catalyzed hydrogen atom transfer (HAT)‐initiated hydrogenation to stereospecifically reduce the tetrasubstituted Δ 10,11 olefin and install the contiguous stereocenters; (5) Fe‐mediated HAT‐initiated 3‐ exo ‐ trig radical cyclization to rapidly forge the tetrasubstituted cyclopropane ring with excellent stereoselectivity.",10.1002/anie.202507961,2025-06-18,0.5865859668328854
European Journal of Organic Chemistry,"Cover Picture: Total Synthesis and Olfactory Evaluation of (1<i>R</i>*,3<i>S</i>*,6<i>S</i>*,7<i>S</i>*,8<i>S</i>*)‐3‐Hydroxy‐6,8‐dimethyltricyclo[5.3.1.0<sup>3,8</sup>]undecan‐2‐one: A New Synthetic Route to the Patchoulol Skeleton (Eur. J. Org. Chem. 6/2006)","Abstract The cover picture shows the ketol soaring above the navel of an oriental belly dancer, which smells not “ like teen spirit ” but actually like patchouli . This is symbolized by the colors the sunlight is refracted into, the colors of the cashmere fabrics with which patchouli leaves first came to Europe. As bifunctional compounds of these molecular dimensions were known to be odorless, the pronounced patchouli odor is indeed very surprising. This ketol is a superstructure of (−)‐patchoulol and a recently discovered high‐impact spirocyclic patchouli odorant, and its odor proves this superposition analysis to be valid. Its total synthesis was accomplished in 13 steps with a total yield of 7% from the inexpensive commercial odorant Cyclal C, and features a novel intramolecular Prins reaction. This unusual access to the tricyclic homoisotwistane skeleton constitutes, in addition, a new formal total synthesis of patchoulol. All details are discussed in the article by P. Kraft et al. on p. 1403 ff.",10.1002/ejoc.200690012,2006-02-28,0.5865842232831875
Tetrahedron,Asymmetric synthesis of chiral sulfoxides and sulfinimines by using N-sulfinylsultam,,10.1016/s0040-4039(97)00472-3,1997-04-01,0.5865789004089058
Tetrahedron,Synthesis of lactosamine from lactulose: scalable approach for the Heyns rearrangement,,10.1016/j.tetlet.2016.04.119,2016-05-07,0.5865769992219965
Synlett,A Synthetic Approach to the Communesins,"A synthetic approach to the communesin family of ­indole alkaoids has been investigated, with a cascade reaction sequence involving formation of a transient 1-alkoxycarbonyl­imidazole intermediate and subsequent addition onto an indole as the key step.",10.1055/s-2008-1078251,2008-08-01,0.5865709042405175
Tetrahedron,"Synthesis of optically pure 2,3,4-trisubstituted tetrahydrofurans via a two-step sequential Michael-Evans aldol cyclization strategy: total synthesis of (+)-magnolone",,10.1016/j.tetlet.2010.03.111,2010-04-07,0.5865646996221487
Organic Letters,"Efficient, Enantioselective Assembly of Silanediol Protease Inhibitors","A five-step assembly of silicon-protected dipeptide mimics from commercially available reagents is described. This methodology makes silanediol protease inhibitors readily available for the first time. The sequence features asymmetric hydrosilylation, a novel reduction of a silyl ether to a silyllithium reagent, and addition of this dianion to a sulfinimine, to produce the complete inhibitor skeleton with full control of stereochemistry. Oxidation of the primary alcohol to an acid completes the synthesis.",10.1021/ol2002978,2011-03-07,0.5865633844439131
Angewandte Chemie International Edition,Total Synthesis of (+)‐Cinereain and (−)‐Janoxepin through a Fragment Coupling/Retro‐Claisen Rearrangement Cascade,"Total syntheses of (+)-cinereain and (-)-janoxepin, two fungal cyclotripeptides featuring a complex heterocyclic core and interesting phytotoxic and antimalarial activities, have been achieved in a convergent manner. A key step in this synthesis is a one-pot cascade initiated by the cyclocondensation of two fragments-a hindered 2-vinylcyclopropane-1-acyl fluoride and an electron-deficient cyclic amidine-to release a reactive spiro[2-vinylcyclopropane-1,5'-pyrimidine-4',6'-dione]. This intermediate underwent a spontaneous retro-Claisen rearrangement that was rationalized by DFT calculations. The cascade directly afforded a 2,5-dihydrooxepin-fused heterotricyclic product, and the challenging oxepin ring was finally forged by the palladium-catalyzed β-hydride elimination of an allylic fluoride intermediate.",10.1002/anie.202212855,2022-09-28,0.5865632973004513
Tetrahedron,Asymmetric synthesis of the lactone moiety of mevinic acid,,10.1016/0040-4039(95)00792-b,1995-06-01,0.5865632104311839
Synthesis,Total Synthesis of (±)-Batzelladine K: A Biomimetic Approach,"Total synthesis of batzelladine K was achieved by a biomimetic approach. The key reactions involve two Wittig reactions of phosphoranes and aldehydes leading to an α,β-unsaturated ketone, followed by a condensation with guanidine. The synthesis was accomplished in four steps with an overall yield of 12%. The relative stereochemistry of batzelladine K was established by NOE experiments and comparison with literature values.",10.1055/s-0029-1218822,2010-06-17,0.5865565312659409
European Journal of Organic Chemistry,"One‐Step Stereospecific Strategy for the Construction of the Core Structure of the 5,11‐Methanomorphanthridine Alkaloids in Racemic as well as in Optically Pure Form: Synthesis of (±)‐Pancracine and (±)‐Brunsvigine","Abstract The unique core structure of the complex pentacyclic 5,11‐methanomorphanthridine has been constructed stereospecifically in one step by an intramolecular [3+2] cycloaddition of a non‐stabilized azomethine ylide (AMY), generated by the sequential double desilylation of 14 using Ag I F as a one‐electron oxidant. The formation of the single diastereomer in the key step is explained by the preferred transition state produced by endo attack of the AMY on the “ Re ” face of the dipolarophile. An asymmetric version of the cycloaddition using a chiral dipolarophile was applied to construct the core structure 68 with 63 % ee . This strategy was successfully applied to the formal synthesis of (±)‐pancracine and the total synthesis of (±)‐brunsvigine. An unprecedented and interesting skeletal rearrangement product 49 was observed during the attempted assembly of the E ring from 46 through Horner–Wadsworth–Emmons reactions. Mechanisms involving azetidinium salt formation or the Grob‐type fragmentation are advanced to explain the observed rearrangement.",10.1002/ejoc.201100601,2011-07-04,0.5865513269360334
Organic Letters,Concise Synthesis of Pauciflorol F Using a Larock Annulation,"A Pd-catalyzed Larock annulation provides expedient access to a subset of resveratrol-derived natural products. The reported approach resulted in the structural revision of an intermediate en route to the natural product pauciflorol F, the total synthesis of which proceeded in two steps from the requisite pentannulation product.",10.1021/ol902141z,2009-11-10,0.5865492246836074
Synlett,Synthesis of New Strapped Porphyrins via a Bisdipyrromethane Condensation,"Two new cationic strapped meso-porphyrins were synthesized via a new route, which consists of the condensation of a bisdipyrromethane with an aldehyde under acidic conditions. One of the strapped porphyrins binds to G-quadruplex DNA.",10.1055/s-2007-967967,2007-02-21,0.5865472209253443
Organic Letters,Synthesis of (±)-Thiohalenaquinone by Iterative Metalations of Thiophene,"The synthesis of a thiophene-containing analogue of halenaquinone was realized. Key steps include an alkynyl ketone-benzocyclobutane Diels-Alder reaction to construct the C,D-ring naphthalene subunit, a Heck cyclization to form the quaternary carbon, and a ring closing metathesis to add the A-ring.",10.1021/ol071258y,2007-07-14,0.5865455773190994
Synlett,Total Synthesis and Structural Revision of Cephalosporolide J,"Abstract Herein, we report the first total synthesis of cephalosporolide J, which is a deep sea sediment derived polyketide harboring a unique bicyclo[3.3.0]furanolactone moiety. The adopted synthetic strategy consisted of the alkynylation of γ-lactone with lithium alkynyltrifluoroborate followed by a spiroketalization triggered by hydrogenation of the triple bond. Through this synthesis, the correct structure of cephalosporolide J is shown to be that of the 9-epi stereoisomer of the structure originally proposed.",10.1055/a-1967-1284,2022-10-24,0.5865414464217916
Journal of Organic Chemistry,Glycosidase Inhibitors:  Synthesis of Enantiomerically Pure Aza-Sugars from Schiff Base Amino Esters via Tandem Reduction-Alkenylation and Osmylation,"Nitrogen-in-the-ring “aza-sugars” have been synthesized in enantiomerically pure form from the amino acid l -alanine in excellent overall yield. The O'Donnell's Schiff base of l -alanine methyl ester 9a was converted to aza-sugar l -fuco-1-deoxy-nojirimycin, 18, and to the epimer l -gulo-1-deoxy-nojirimycin, 20, in eight steps. The overall yields were 20 and 29%, respectively. The methodology for the efficient generation of silyl- and benzyl-protected ( E )-3-lithio-2-propen-1-ols, and the use of these alkenyllithiums with iBu 5 Al 2 H as nucleophiles in the threo -selective tandem reduction−alkenylation of the Schiff base esters is described. Osmium-catalyzed cis -oxygenation of the resulting olefin products was selective for the galacto ( fuco ) amino polyols in all cases for the acyclic olefins, and was gulo -selective for the cyclic D-4,5-dihydropyridine pivalate, 17c . TEMPO-NaOCl was selective for oxidation of the primary position of the acyclic Schiff bases, and allowed for minimal protection/deprotection of the intermediates. The resulting N -benzhydryl heterocycles were easily deprotected with H 2 −Pd at atmospheric pressure.",10.1021/jo9820115,1999-08-01,0.5865369507880785
Journal of Organic Chemistry,"Synthesis of Norcarbovir Analogues, the First Examples of Cyclobutene Nucleosides Unsubstituted at the Vinylic Position","Two cyclobutene nucleosides, 27 and 29, analogous to the yet unknown norcarbovir, and with adenine and hypoxanthine as the base moieties, respectively, were synthesized starting from cis-3-cyclobutene-1,2-dicarboxylic anhydride (6). Its reduction to lactone 9 followed by reaction with ammonia and then Hofmann rearrangement led to cyclic carbamate 15 which was the key intermediate of these syntheses. Its tert-butoxycarbonyl derivative 17 led to the ring opening of the heterocyclic moiety at low temperature. Compound 18 was thus obtained, and the successive benzylation and then treatment with hydrochloric acid yielded hydrochloride 21. Construction of bases was achieved in satisfying overall yields provided that mild experimental conditions from 21 to 27 or 29 were used to restrict the unwanted electrocyclic ring opening. Nitropyrimidine 31 was also prepared from 21 via the intermediate 23.",10.1021/jo961451y,1997-04-01,0.5865260154927053
Journal of Organic Chemistry,Regiospecific Synthesis of 2-Halo-3-(2′-glucalyl)benzo[<i>b</i>]thiophenes,A regiospecific synthetic strategy for the synthesis of 2-chloro-3-substituted benzo[b]thiophenes is developed via a dichlorocarbene insertion and sigmatropic rearrangement of an in situ generated ylide. The current protocol provides a reversed regiochemistry to the commonly employed electrophilic cyclization reaction for the synthesis of benzo[b]thiophenes and access to their hitherto under-represented chlorinated derivatives.,10.1021/jo5012762,2014-07-21,0.5865242063018727
Tetrahedron,Synthesis of bicyclic cyclophanes with chiral cages by sixfold coupling,,10.1016/s0040-4039(02)00137-5,2002-03-01,0.5865152102033606
Organic Letters,A New β-Carbolinone Synthesis Using a Rh(II)-Promoted [3 + 2]-Cycloaddition and Pd(0) Cross-Coupling/Heck Cyclization Chemistry,"[reaction: see text]. A short and efficient synthesis of the beta-carbolinone ring system was achieved using a rhodium(II)-catalyzed [3 + 2]-cycloaddition, a Pd(0)-catalyzed C-N amination reaction, and a subsequent intramolecular Heck reaction as the key synthetic steps.",10.1021/ol0356338,2003-10-01,0.5865145415839774
Organic Letters,Suppressed β-Hydride Elimination in Palladium-Catalyzed Cascade Cyclization−Coupling Reactions:  An Efficient Synthesis of 3-Arylmethylpyrrolidines,"[formula: see text] A novel type of palladium-catalyzed cascade cyclization-coupling reaction that proceeds with suppressed beta-hydride elimination has been found. One of the N-sulfonyl oxygens is suggested to coordinatively stabilize an alkylpalladium intermediate, thus preventing the intermediate from the usual beta-elimination. This is the first sequential palladium-catalyzed coupling reaction where the Suzuki and Heck reactions can compete. The reaction provides an efficient synthetic route to 4-methylene-3-arylmethylpyrrolidines, which are not readily available by other routes.",10.1021/ol0056426,2000-04-14,0.586514498490936
Tetrahedron,Complexation of ATP to a Synthetic [15]-N3 Macrocyclic Polyammonium Receptor,,10.1016/s0040-4039(00)82312-6,1988-01-01,0.5865113046592847
Angewandte Chemie International Edition,Neuritogenic Militarinone‐Inspired 4‐Hydroxypyridones Target the Stress Pathway Kinase MAP4K4,"Progressive loss and impaired restoration of neuronal activity are hallmarks of neurological diseases, and new small molecules with neurotrophic activity are in high demand. The militarinone alkaloids and structurally simplified analogues with 4-hydroxy-2-pyridone core structure induce pronounced neurite outgrowth, but their protein target has not been identified. Reported herein is the synthesis of a militarinone-inspired 4-hydroxy-2-pyridone collection, its investigation for enhancement of neurite outgrowth, and the discovery of the stress pathway kinase MAP4K4 as a target of the discovered neuritogenic pyridones. The most potent 4-hydroxy-2-pyridone is a selective ATP-competitive inhibitor of MAP4K4 but not of the other stress pathway related kinases, as proven by biochemical analysis and by a crystal structure of the inhibitor in complex with MAP4K4. The findings support the notion that MAP4K4 may be a new target for the treatment of neurodegenerative diseases.",10.1002/anie.201501515,2015-04-23,0.5865010372579522
Tetrahedron,Synthetic studies towards anti-SARS agents: application of an indium-mediated allylation of α-aminoaldehydes as the key step towards an intermediate,,10.1016/j.tetlet.2004.10.146,2004-11-12,0.5864939152804084
Synthesis,"Lewis Acid Catalyzed SN2-Type Domino Ring-Opening Cyclization (DROC) of Aziridines with Alkynes: A Synthetic Route to 2,3-Dihydropyrroles","Abstract A simple strategy for the synthesis of a variety of dihydropyrroles in good to excellent yields via a Lewis acid catalyzed, quaternary ammonium salt mediated SN2-type ring opening followed by cyclization of activated aziridines with alkynes in a domino fashion is described. The formation and the observed stereoselectivities of the products via an SN2-/double SN2-type ring-opening pathway are rationalized by mechanistic studies.",10.1055/a-2415-1629,2024-09-13,0.5864810064208917
Tetrahedron,Synthesis via oxazolines. VI. An asymmetric synthesis of β-hydroxy and β-methoxy alkanoic acids,,10.1016/s0040-4039(01)82481-3,1974-01-01,0.5864806462541243
Synthesis,Regiospecific Synthesis of Dihydropyrroles,"All articles of this category A regiospecific synthesis of substituted dihydropyrroles is reported via nucleophilic homoallylic addition of activated cyclopropanes, followed by intramolecular ß-enamino ester formation.",10.1055/s-1992-26252,1992-01-01,0.5864781378108601
Synthesis,Synthesis of New Camphor-Based Carbene Ligands and Their Application in a Copper-Catalyzed Michael Addition with B2Pin2,"In this work the synthesis of new asymmetric camphor-based carbene ligands from camphoric acid is described. The new carbenes can be prepared directly in high yields by the sequence: regioselective arylation of the less hindered primary amine group of (+)- cis -1,2,2-trimethylcyclopentane-1,3-diamine by Buchwald–Hartwig amination, treatment with trimethyl orthoformate, and finally treatment with a benzylic halide. The resulting carbenes, incorporating an aryl and a benzylic substituent, were successfully applied as ligands in a copper-catalyzed B 2 Pin 2 [bis(pinacolato)diboron] addition to an unsaturated carbonyl compound. Depending on the substituents dual stereocontrol was observed and one enantiomer was obtained in up to 82% ee and the opposite enantiomer in up to 78% ee.",10.1055/s-0034-1379877,2014-12-22,0.5864674289389994
Tetrahedron,Synthesis of chiral subunits for macrolide synthesis: an efficient method for converting spiroketals into open-chain derivatives,,10.1016/s0040-4039(00)87644-3,1982-01-01,0.5864658079872666
Synthesis,Enantiospecific Synthesis of Both Enantiomers of 2-Benzyloxydihydropyran-3-ones from Arabinose,"Approaches to the enantioselective synthesis of the useful building blocks (2R)- and (2S)-2-benzyloxy-2(H)-pyran-3(6H)-one (12 and 17, respectively) are described. The most direct and highly yielding route for the synthesis of 12 was based on the ‘one-pot’ preparation of benzyl 2-O-acetyl-arabinopyranoside 3,4-thio­nocarbonates (7 and 14) from benzyl β-l- or β-d-arabinopyranosides (1 and 13). Trimethylphosphite-promoted olefination, followed by O-deacetylation and oxidation gave the optically pure enantiomeric enones 12 and 17 in about 50% overall yield.",10.1055/s-2005-861833,2005-01-01,0.5864637955481121
Journal of the American Chemical Society,New Synthetic Technologies for the Construction of Heterocycles and Tryptamines,"New synthetic methods for the construction of novel heterocycles and tryptamines are described. Thus, N-Boc anilines (I) are sequentially converted to heterocycles II ((3-(2-aminophenyl)pyrrolidin-3-ol) derivatives), III (substituted 2-oxo-1,2-dihydrospirobenzo[d][1,3]oxazine-4,3'-pyrrolidines), and VI (2-(4,5-dihydro-1H-pyrrol-3-yl)aniline) derivatives through a route involving t-BuLi induced ortho-metalation/LaCl(3).2LiCl metal exchange, reaction with N-Boc pyrrolidin-3-one (5), and subsequent decarboxylative fragmentation. Labile intermediates VI are effectively converted to tryptamines Xa and Xb under controlled protic acid conditions. In addition to providing expedient access to the 2-oxo-1,2-dihydrospirobenzo[d][1,3]oxazine-4,3'-pyrrolidines (III), the method is applicable to the synthesis of the corresponding 2-oxo-1,2-dihydrospirobenzo[d][1,3]oxazine-4,3'-piperidine series of spirocycles (e.g., 42) and their precursors (3-(2-aminophenyl)piperidin-3-ol derivatives, e.g., 43) by using N-Boc-protected piperidin-3-one (40). Applications of the developed synthetic technologies to the synthesis of regioisomeric spirocycles 87 and 90, tryptamines 88 and 91, Corey's aspidophytine tryptamine (97), and efavirenz (1) are also described.",10.1021/ja808692j,2009-02-25,0.5864541605894996
Journal of the American Chemical Society,Total Synthesis of (−)-Pseudolaric Acid B,"We report the enantioselective synthesis of pseudolaric acid B (1a), a diterpene acid isolated from the bark of Pseudolarix kaempferi Gordon, which displays interesting antifungal, antifertility, and cytotoxic activity against multidrug resistant cell lines. Our synthesis utilizes a highly efficient metal-catalyzed [5 + 2] vinylcyclopropane-alkyne intramolecular cycloaddition to construct the polyhydroazulene core of the natural product. Elaboration to the tricyclic scaffold of the pseudolaric acids was completed with an intramolecular alkoxycarbonyl radical cyclization to form the quaternary center and a highly diastereoselective cerium acetylide addition to a methyl ketone for introduction of the acid side chain.",10.1021/ja076165q,2007-11-07,0.5864538908074022
European Journal of Organic Chemistry,Total Synthesis of a Pentasaccharide O‐Glycan from <i>Acinetobacter baumannii</i>,"Abstract Acinetobacter baumannii is a Gram‐negative bacteria associated with drug resistance and infection in healthcare settings. An understanding of both the biological roles and antigenicity of surface molecules of this organism may provide an important step in the prevention and treatment of infection through vaccination or the development of monoclonal antibodies. With this in mind, we have performed the multistep synthesis of a conjugation‐ready pentasaccharide O ‐glycan from A. baumannii with a longest linear synthetic sequence of 19 steps. This target is particularly relevant due to its role in both fitness and virulence across an apparently broad range of clinically relevant strains. Synthetic challenges include formulating an effective protecting group strategy as well as the installation of a particularly difficult glycosidic linkage between the anomeric position of a 2,3‐diacetamido‐2,3‐dideoxy‐D‐glucuronic acid and the 4‐position of D‐galactose.",10.1002/ejoc.202201261,2022-12-16,0.5864486573706764
Organic Process Research & Development,A New Addition Compound of Desloratadine with Carbon Dioxide,"The addition compound of 8-chloro-6,11-dihydro-11-(4-piperidylidene)-5 H -benzo[5,6]cyclohepta[1,2- b ]pyridine (descarboethoxyloratadine, desloratadine) with CO 2, in molar ratio 2:1, is described. This unique form of desloratadine drug substance can be prepared in exceedingly high purity by a simple process from crude desloratadine. The addition compound is a useful intermediate in the manufacturing process of desloratadine Form I polymorph. An improved, environmental friendly manufacturing process for the synthesis of desloratadine starting from loratadine is also disclosed here.",10.1021/op8001036,2008-08-06,0.5864353139321221
European Journal of Organic Chemistry,Synthesis of Highly Substituted Methylenecyclohexenes Using New Domino Reactions with Sultones,"New methods for the synthetic elaboration of sultones with concomitant desulfurization have been developed. Alkylation of sultones with (iodomethyl)trimethylsilane followed by treatment of the resultant silyl compound with tetrabutylammonium fluoride gave rise to sulfur-free methylenecyclohexenes. In a more straightforward fashion, highly substituted compounds of the latter type were readily accessible by alkylation of α-metallated allylic sultones prepared either by deprotonation, radical cyclization/transmetallation, or conjugate 1,6-addition with (iodomethyl)magnesium chloride in a one-pot transformation. An advanced intermediate for the synthesis of several 1,10-seco-eudesmanolides was rapidly constructed using such a protocol.",10.1002/1099-0690(200110)2001:19<3669::aid-ejoc3669>3.0.co;2-s,2001-10-01,0.5864324549002266
Organic Letters,Total Synthesis of (−)-Teucvidin,"A concise enantioselective synthesis of (-)-teucvidin has been achieved. Our synthetic strategy involved the diastereoselective Michael/Conia-ene cascade cyclization reaction for rapid establishment of the cis-decalin skeleton with three new stereogenic centers in one pot (72%, single diastereomer), the epoxidation/dealkoxycarbonylation protocol for construction of the fused furanone moiety, and the O-allylation/Claisen rearrangement protocol for construction of the all-carbon quaternary center at C9 of the clerodane skeleton.",10.1021/ol301098s,2012-05-17,0.5864308060063561
Organic Letters,Dragmacidin E Synthesis Studies. Preparation of a Model Cycloheptannelated Indole Fragment,"[reaction: see text] The conversion of N-2,2-dichloropropionyl indole methyl ester into a tetracyclic cycloheptannelated indole model compound for the synthesis of dragmacidin E was accomplished in 10 steps. Key reactions include a Witkop cyclization to fashion a C-C bond at C(4) of the indole nucleus and a subsequent Dieckmann cyclization to deliver the desired cycloheptanoid ring.",10.1021/ol0522081,2005-10-27,0.5864251657820284
Angewandte Chemie International Edition,Total Synthesis of the Thiazolyl Peptide GE2270 A,"When one door closes, another opens: In the synthesis of the thiazolyl peptide GE2270 A (1), the bonds labeled I and II at the pyridine core were established by two consecutive cross-coupling reactions. Amide bond formation (IV) and subsequent intramolecular Stille reaction (III) were more effective than the originally conceived connection strategy (III before IV). GE2270 A (1) was prepared with an overall yield of 4.8 % in 20 steps along the longest linear sequence.",10.1002/anie.200700684,2007-05-14,0.5864224541428217
Tetrahedron,Synthesis of angularly-fused aromatic antibiotics. Preparation of the ABC ring system of aquayamycin,,10.1016/s0040-4039(97)01516-5,1997-09-01,0.5864171836712855
Journal of Organic Chemistry,Total Synthesis of (+)-Goniodenin,Goniodenin is a lipophilic polyketide originating from plant sources and which possesses a potent cytotoxic activity against cancer cell lines. The first total synthesis of (+)-goniodenin has been achieved in 23 steps from ( R )-glycidol. The synthetic sequence featured a cross metathesis for the formation of the C 8 –C 9 bond and installation of the terminal γ-butenolactone ring unit by the alkylation of α-phenylthio-γ-butyrolactone with the corresponding C 3 - O -triflate. The stereogenic center at C 18 carbon was created by Hiyama–Fujita reduction of the corresponding ketone with high diastereoselectivity.,10.1021/acs.joc.6b02432,2016-11-21,0.5864124664219938
Tetrahedron,Synthesis of thiooxamates from t-butyl sulfinamoyl acetates. Occurrence of a new rearrangement involving a thione S-imide intermediate,,10.1016/s0040-4039(00)97646-9,1990-01-01,0.586412297507623
European Journal of Organic Chemistry,Unified Synthesis of Densely Functionalized Amino Acid Building Blocks for the Preparation of Caprazamycin Nucleoside Antibiotics,"Naturally occurring caprazamycin nucleoside antibiotics are promising lead structures for the development of novel antimicrobial agents. However, efficient synthetic access to the structurally complex caprazamycin scaffold is not trivial. The stereocontrolled construction of the seven‐membered diazepanone core moiety is particularly challenging. So far, two main strategies to build up the diazepanone system (by reductive amination or Mitsunobu reaction) have been established, but they require different non‐proteinogenic amino acid building blocks to be connected with the nucleoside moiety. Previously, these amino acid structures were obtained from different starting materials with no overlap of the according synthetic routes. In this work, we describe an efficient unified synthetic access to densely functionalized amino acid building blocks for both approaches towards the diazepanone core. This will enable the preparation of caprazamycin analogues with high modularity and variability.",10.1002/ejoc.201801667,2019-01-09,0.5864074539046714
Journal of Organic Chemistry,Practical Synthesis of Enantiopure Spiro[4.4]nonane <i>C</i>-(2‘-Deoxy)ribonucleosides,"The levorotatory diol 7 has been sequentially monosilylated, dehydrated, and oxidized at the allylic methylene group to provide (+)-12. The enantiomeric dextrorotatory diol 7 has been directed down a different sequence of steps involving monosilylation, dehydration, hydroboration, Swern oxidation, and regioselective introduction of a conjugated double bond to generate (-)-33. The novel feature of these transformations is that two key deoxycarbospironucleoside intermediates of the proper absolute configuration have been made available from enantiomerically related precursors. Also reported is a highly practical and reliable means for the formation of novel 2'-deoxyribonucleosides of novel structural type from these spirocyclic cyclopentenones.",10.1021/jo0480601,2005-02-02,0.5864049161175923
Journal of Organic Chemistry,"Total Synthesis of (−)-Clavicipitic Acid via γ,γ-Dimethylallyltryptophan (DMAT) and Chemoselective C–H Hydroxylation","The first total synthesis of natural (−)-clavicipitic acid from γ,γ-dimethylallyltryptophan (DMAT), its biosynthetic precursor, is described. This is done by regio- and chemoselective, remote, nondirected C(sp 3 )–H hydroxylation followed by aminocyclization. This study also features regio- and chemoselective Pd(0)-catalyzed linear prenylation at C4 of l -tryptophan boronic pinacol ester derivate, the latter obtained by a Lewis acid-promoted aziridine amino acid ring opening with 4-boronated indole. In addition, these results support the hypothesis that oxidative cyclization between amino acid nitrogen and the prenyl chain during clavicipitic acid biosynthesis can occur through the transient hydroxylated intermediate.",10.1021/acs.joc.9b00879,2019-05-23,0.5864047022022604
Tetrahedron,A new strategy for the enantioselective synthesis of aspidosperma alkaloids: I - Construction of the [ABC]-type tricyclic intermediates.,,10.1016/s0040-4039(00)94653-7,1990-01-01,0.5864043901648812
Tetrahedron,Regioselective N-alkylation of benzimidazole via an organotin route,,10.1016/s0040-4039(01)81624-5,1984-01-01,0.5863776459707974
Journal of Organic Chemistry,"Dearomative Alkylation-Based Two-Step <i>cis</i>-Diastereoselective Synthesis of Indoline-2,3-Fused Chromans and Tetrahydropyrans","Herein, we describe a two-step, cis -diastereoselective synthesis of indoline-2,3-fused chromans from 3-substituted indoles. The method proceeds without intermediacy of ortho -quinone methides and leverages the dual function of TBS-protected 2-hydroxybenzyl iodides both as highly reactive alkylating agents in a t -BuONa/Et 3 B-promoted dearomative alkylation step and as a source of masked phenoxide nucleophiles in a subsequent TBAF-induced one-pot deprotection-cyclization step of the resulting indolenines. Importantly, this two-step protocol can also be extended to access indoline-2,3-fused tetrahydropyrans. These syntheses of indoline-2,3-fused chromans and tetrahydropyrans proceed with operational convenience, use easily accessible substrates and reagents, and feature broad substrate scope, high yields and complete diastereoselectivity. Furthermore, the synthesized products have the potential to undergo late-stage functionalization.",10.1021/acs.joc.4c01726,2024-10-03,0.5863724950648495
Journal of Organic Chemistry,Total Synthesis and Bioactivity of an Unnatural Enantiomer of Merrilactone A:  Development of an Enantioselective Desymmetrization Strategy,"(-)-Merrilactone A [(-)-1], isolated from Illicium merrillianum in 2000, possesses neurite outgrowth activity in cultures of fetal rat cortical neurons, and, therefore, is expected to show therapeutic potential for the treatment of neurodegeneration associated with Alzheimer's and Parkinson's diseases. Apart from its biological aspects, the caged pentacyclic skeleton of 1 poses interesting synthetic challenges. Here, we report the total synthesis of the unnatural enantiomer of merrilactone A [(+)-1], based on a novel desymmetrization strategy. The chiral lithium amide 16g promoted an enantioselective transannular aldol reaction of eight-membered meso-diketone 3d, establishing the absolute stereochemistries of four chiral centers of the cis-bicyclo[3.3.0]octane framework of 1 in a single step. The obtained compound 4d served as a platform for the subsequent functional group manipulations necessary for the construction of (+)-1. Surprisingly, both the natural and unnatural enantiomers of synthetic merrilactone A equally promoted neurite outgrowth in primary neuronal cultures.",10.1021/jo0700474,2007-03-14,0.5863722800464334
Journal of the American Chemical Society,Enantioselective Total Synthesis of (−)-Arcutinine,"-diterpenoid alkaloid arcutinine has been achieved in both racemic and asymmetric forms. Construction of the C4 quaternary center and the pyrrolidine E ring in an early stage proved to be important for achieving the successful synthesis of the target alkaloid. Strategically, an asymmetric conjugate addition/aldol cascade and a decarboxylative allylation reaction allowed the establishment of the vicinal all-carbon quaternary stereocenters at C4 and C5. Furthermore, a sequence consisting of an intramolecular aza-Wacker cyclization, an oxidative dearomatization/intramolecular Diels-Alder cycloaddition cascade, and a ketyl-olefin cyclization enabled the assembly of the core structure and led to the total synthesis of arcutinine.",10.1021/jacs.9b04847,2019-05-28,0.5863721526068219
Journal of Organic Chemistry,"Enantioselective Total Synthesis of the Mexicanolides: Khayasin, Proceranolide, and Mexicanolide","The enantioselective total synthesis of the limonoids khayasin, proceranolide and mexicanolide was achieved via a convergent strategy utilizing a tactic aimed at incorporating natural products as advanced intermediates. This extended biomimetically inspired approach additionally achieved the enantioselective total synthesis of the intermediates azedaralide and cipadonoid B.",10.1021/jo301182f,2012-09-20,0.5863699901841317
Journal of Organic Chemistry,A Synthetic Approach to the Fusicoccane A−B Ring Fragment Based on a Pauson−Khand Cycloaddition/Norrish Type 1 Fragmentation,"A synthetic approach to the A-B ring system within the fusicoccane family of diterpenes is presented. Key steps in this approach are a diastereoselective Pauson-Khand reaction, a Norrish 1 photofragmentation, a Charette cyclopropanation, and a ring-closing metathesis process.",10.1021/jo800933f,2008-07-25,0.5863681884913946
Journal of the American Chemical Society,Expedient Total Syntheses of Pladienolide-Derived Spliceosome Modulators,"Atom and step economical total syntheses of spliceosome modulating natural products pladienolides A and B are described. The strategic functionalization of an unsaturated macrolide precursor enabled the most concise syntheses of these natural products to date and provides convenient, flexible access to stereodefined macrolides to streamline medicinal chemistry explorations. Notably, this synthetic route does not depend on protecting group manipulations that traditionally define synthesis planning for polyhydroxylated natural products of polyketide origin. Its utility is further demonstrated by the enantioselective total synthesis of H3B-8800, a hitherto semisynthetic pladienolide-derived spliceosome modulator undergoing clinical trials for hematological malignancies.",10.1021/jacs.1c01135,2021-03-23,0.5863666631756413
Synthesis,A Viable Route to exo-2-Benzyliminobornan-3-ol: A Key Intermediate in the Synthesis of a Chiral Auxiliary,"All articles of this category A new synthesis of the title compound 2 has been achieved in which benzylamine reacts with the novel hydroxy N -nitroimine 6 with concomitant evolution of nitrous oxide, whereas the published reaction between benzylamine and the corresponding ketone 4 does not occur reproducibly. benzylamine - hydroxy N -nitroimine - exo -2-benzylimino-bornan-3-ol - chiral auxiliary - nitrous oxide",10.1055/s-1997-1404,1997-06-01,0.5863661744454032
Tetrahedron,Total synthesis of the sesquiterpene (±)β-cuparenone: use of three-carbon annulation in synthesis,,10.1016/s0040-4039(00)92183-x,1980-01-01,0.5863641178267062
Angewandte Chemie International Edition,Total Synthesis of Trioxacarcin DC‐45‐A2,"An enantioselective total synthesis of trioxacarcin DC-45-A2 (1) featuring a novel Lewis acid-induced cascade rearrangement of epoxyketone 6 to forge the polyoxygenated 2,7-dioxabicyclo[2.2.1]heptane core of the molecule is described.",10.1002/anie.201410369,2015-01-12,0.5863625063294027
Tetrahedron,"A general synthetic route towards bastadins. Part 2: Synthesis of the western part of bastadins 4–16, and fully functionalized macrocycle of bastadin 12",,10.1016/s0040-4039(99)01430-6,1999-09-01,0.5863584139000907
Journal of Organic Chemistry,Carbohydrate-Based Macrolides Prepared via a Convergent Ring Closing Metathesis Approach:  In Search for Novel Antibiotics,"An efficient convergent approach has been developed for the construction of novel, nonnatural polysubstituted carbohydrate-based macrolides. A key step in the synthesis is the formation of the macrocyclic ring via a ring-closing metathesis reaction. The obtained macrolide analogues have been screened for biological activity against gram-positive and gram-negative bacteria, yeasts, and molds.",10.1021/jo061929q,2007-06-21,0.5863561493308599
Tetrahedron,Synthesis in the series of diterpene alkaloids. IX. A new simple synthesis of veatchine,,10.1016/s0040-4039(00)75452-9,1968-01-01,0.5863539192426811
Organic Letters,Expedient Synthesis of (±)-Bipinnatin J,"[reaction: see text] A nine-step, stereoselective synthesis of bipinnatin J is described, which features a ruthenium-catalyzed Alder-ene reaction, a Stille cross coupling, and an intramolecular Nozaki-Hiyama-Kishi allylation as key steps. The biosynthetic relationship between bipinnatin J and complex polycyclic diterpenes isolated from gorgonian corals is discussed.",10.1021/ol052922i,2005-12-16,0.5863490661970607
Angewandte Chemie International Edition,Total Synthesis of the Callipeltoside Aglycon,"Following macrolactonization, a Sonogashira coupling leads efficiently from 1 and 2 to the aglycon of the structurally unique cytotoxic macrolide callipeltoside A, isolated in tiny quantities from the lithistid sponge Callipelta sp. Key steps in the preparation of macrolide precursor 1 include a boron-mediated anti-aldol coupling (A) in tandem with Yamamoto's vinylogous aldol reaction (B). TES=triethylsilyl.",10.1002/1521-3773(20010202)40:3<603::aid-anie603>3.3.co;2-f,2001-02-02,0.5863454902241997
Angewandte Chemie International Edition,Total Synthesis of the Callipeltoside Aglycon,"Following macrolactonization, a Sonogashira coupling leads efficiently from 1 and 2 to the aglycon of the structurally unique cytotoxic macrolide callipeltoside A, isolated in tiny quantities from the lithistid sponge Callipelta sp. Key steps in the preparation of macrolide precursor 1 include a boron-mediated anti-aldol coupling (A) in tandem with Yamamoto's vinylogous aldol reaction (B). TES=triethylsilyl.",10.1002/1521-3773(20010202)40:3<603::aid-anie603>3.0.co;2-o,2001-01-30,0.5863454902241997
Organic Letters,Synthesis of Fluorenone Derivatives through Pd-Catalyzed Dehydrogenative Cyclization,"Palladium-catalyzed dual C-H functionalization of benzophenones to form fluorenones by oxidative dehydrogenative cyclization is reported. This method provides a concise and effective route toward the synthesis of fluorenone derivatives, which shows outstanding functional group compatibility.",10.1021/ol302181z,2012-08-31,0.5863448959072987
Journal of Organic Chemistry,Substrate Controlled Synthesis of Benzisoxazole and Benzisothiazole Derivatives via PhI(OAc)<sub>2</sub>-Mediated Oxidation Followed by Intramolecular Oxidative O–N/S–N Bond Formation,"A phenyliodine(III) diacetate (PIDA)-mediated, highly efficient and tandem approach for the synthesis of aryldiazenylisoxazolo(isothiazolo)arenes from simple 2-amino-N'-arylbenzohydrazides has been developed. The reaction proceeds via formation of (E)-(2-aminoaryl)(aryldiazenyl)methanone as the key intermediate, followed by intramolecular oxidative O-N/S-N bond formation in one pot at room temperature. The quiet different reactivity of the substrate is due to the formation of a diazo intermediate which encounters a nucleophilic attack by carbonyl oxygen on the electrophilic amine to produce isoxazole products, as compared to the previous reportsa,b,4 in which an N-acylnitrenium ion intermediate is intramolecularly trapped by an amine group.",10.1021/acs.joc.5b02276,2015-11-13,0.5863372780693098
European Journal of Organic Chemistry,Synthetic Studies on Cyathin Terpenoids: Enantioselective Synthesis of the Tricyclic Core of Cyathin through Intramolecular Heck Cyclisation,"Abstract An enantioselective synthesis of the tricyclic ketone (+)‐ 5 , which displays the carbon core of NGF‐inducing cyathane diterpenes, has been completed according to a strategy in which the key step was the intramolecular Heck reaction of the AC subunit 49 establishing the crucial anti stereochemical relationship between the two angular substituents. The C‐9 quaternary centre was set up by taking advantage of the enantioselective Michael addition involving chiral imines providing keto ester ( R )‐ 10 in 91 % ee . After incorporation of the isopropyl group and iododecarboxylation of the propionate side chain, the iodo ketone 39 was condensed with the lithium enolate of methyl dihydrobenzoate to give the AC subunit 43 which was further elaborated to triflate (–)‐ 22 . While direct Heck cyclisation of 22 was ineffective, oxidation of the bis(allylic) position of the 1,4‐cyclohexadiene moiety enhanced the reactivity, allowing the stereoselective formation of the hexahydro‐cyclopenta[ a ]naphthalene (+)‐ 50a . A key element of the construction was the final C ring enlargement, involving trimethylaluminum‐promoted one‐carbon expansion of ketone 52 with trimethylsilyldiazomethane which provided the tricyclic ketone (+)‐ 5 . Furthermore, epoxidation of trienone (+)‐ 50a was shown to occur exclusively on the β face, giving rise to the C‐14 functionalised advanced intermediate 51 which has considerable potential for the synthesis of natural cyathins and analogues.(© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2006)",10.1002/ejoc.200600429,2006-09-05,0.5863348242635069
Organic Letters,Asymmetric Total Synthesis of Lepadiformine C Using Memory of Chirality in an Intramolecular Ester Enolate Michael Addition,"The asymmetric synthesis of lepadiformine C was achieved using d-proline as the only chiral source. The synthetic strategy features the use of the principle of ""memory of chirality"" in an intramolecular Michael addition to construct the bicyclic intermediate without the aid of external chiral sources. A brief mechanistic rationale is presented to account for the stereochemical outcome.",10.1021/acs.orglett.6b03550,2016-12-21,0.5863323664971785
Tetrahedron,"Highly efficient, multigram and enantiopure synthesis of (S)-2-(2,4′-bithiazol-2-yl)pyrrolidine",,10.1016/j.tetlet.2011.07.128,2011-08-16,0.5863280697902383
Synthesis,"Short and Efficient Synthesis of Enantiomerically Pure 4-Substituted (1<i>E</i>,3<i>E</i>)-1[(<i>R</i>)-<i>p</i>-Tolylsulfinyl]-1,3-butadienes","All articles of this category The title compounds were readily prepared in two steps by the condensation of (+)-methyl p -tolyl ( R )-sulfoxide to α,β-unsaturated aldehydes followed by a one-pot dehydration of the resulting β-hydroxy sulfoxides.",10.1055/s-1991-26633,1991-01-01,0.5863209255083359
Synlett,Synthetic Studies towards Iriomoteolide-1a: Construction of the C13-C23 Fragment,"A stereoselective synthesis of the C13-C23 segment of iriomoteolide-1a was achieved using, as key steps, a highly stereocontrolled crotylation to build the stereocenters at C18 and C19 and a Julia-Kocienski olefination to establish the C15-C16 E-olefin moiety.",10.1055/s-0029-1217728,2009-08-27,0.5863191357428919
Angewandte Chemie International Edition,The Total Synthesis of Inostamycin A,"The first total synthesis of inostamycin A is described. With efficient and stereoselective synthetic routes to aldehyde 3 and ketone 4 developed through asymmetric aldol reactions, addition reactions and reduction, and with chiral building blocks, the two large fragments were coupled with remarkable anti stereoselectivity and efficiency by aldol condensation. The coupling reaction provided the complete carbon skeleton with all the requisite functional groups and stereogenic centers for inostamycin A. The two quaternary carbons at C20 and C16 of ketone 4 were elaborated in a highly stereocontrolled manner by addition reactions of the transmetallated 5 to ethyl ketone 6 and the transmetallated 7 to methyl ketone 8, respectively, in which the use of LaCl3 for transmetallation was critical for high coupling efficiency.",10.1002/anie.201510852,2016-01-22,0.5863108527453428
Journal of Organic Chemistry,Synthesis of a Polycyclic Halichondrin C1–C14 Fragment via Intermolecular Oxy-Michael/<i>Trans</i>-Ketalization,"Syntheses of a crystalline polycyclic halichondrin C1-C14 building block starting from a d-gulono-1,4-lactone-derived intermediate in the current Halaven manufacturing process are described. Key features of the syntheses include an acid-catalyzed tandem intermolecular oxy-Michael/intramolecular trans-ketalization reaction and stereoselective Kishi reductions.",10.1021/acs.joc.8b02404,2018-11-05,0.5863043147979218
Journal of Organic Chemistry,Diastereoselective Friedel–Crafts Alkylation of Hydronaphthalenes,"An efficient and versatile synthesis of chiral tetralins has been developed using both inter- and intramolecular Friedel-Crafts alkylation as a key step. The readily available hydronaphthalene substrates were prepared via a highly enantioselective metal-catalyzed ring opening of meso-oxabicyclic alkenes followed by hydrogenation. A wide variety of complex tetracyclic compounds have been isolated with high levels of regio-, diastereo-, and enantioselectivity.",10.1021/jo201781x,2011-09-27,0.5862968224851236
Tetrahedron,A simple route to chiral phosphonothionates from diastereomeric phosphonamidothionates,,10.1016/s0040-4039(00)60751-7,1994-06-01,0.5862962197964955
Tetrahedron,A short practical synthesis of 2′-deoxymugineic acid,,10.1016/j.tetlet.2005.01.030,2005-01-29,0.5862951049693603
Journal of the American Chemical Society,Concise Synthesis of (−)-GA<sub>18</sub> Methyl Ester,"Gibberellins (GAs) are important plant hormones, but some of their family members are in extremely limited natural supply including GA 18 . Herein, we report a concise synthesis of (−)-GA 18 methyl ester, a member of the C 20 gibberellins, from commercially available and cheap andrographolide. Our synthesis features an intramolecular ene reaction to form the C ring, an oxidative cleavage followed by aldol condensation to realize a ring contraction and form the challenging trans -hydrindane (AB ring), and a photochemical [2+2] cycloaddition accompanied by a subsequent SmI 2 -mediated skeletal rearrangement to construct the methylenebicyclo[3.2.1]octanol moiety (CD ring).",10.1021/jacs.2c12470,2022-12-27,0.5862914656679941
Organic Letters,A Synthetic Route to The Core Structure of (−)-Retigeranic Acid A,"Retigeranic acid A is a uniquely structured pentacyclic sesterterpene bearing eight stereogenic centers. We report a concise route to the core structure of (−)-retigeranic acid A. The stereochemistry of its six chiral centers and three quaternary carbon centers was well-controlled. This route features two intramolecular Pauson–Khand reactions (IMPKRs): the first forged the D and E rings to deliver the triquinane subunit, and the second constructed the A and B rings and diastereoselectively installed the quaternary C 6a center.",10.1021/acs.orglett.1c01633,2021-06-15,0.586288661012047
Tetrahedron,"Synthesis of new fluorescent 1-(thien-2-yl)-9H-thieno[3,4-b]-chroman-9-ones and their fluorescent photomodulation by photochromic dihetarylethenes",,10.1016/j.tetlet.2015.01.101,2015-01-23,0.5862853470845929
Angewandte Chemie International Edition,"Synthesis of Neocaesalpin A, AA, and Nominal Neocaesalpin K**","The first total synthesis of heavily oxidized cassane-type diterpenoid neocaesalpin A (1) is disclosed. At the heart of the synthesis lies an intermolecular Diels-Alder reaction that rapidly assembles the target framework from commercial materials. A carefully orchestrated sequence of oxidations secured the desired oxygenation pattern. Late-stage release of the characteristic butenolide occurred through a novel mercury(II)-mediated furan oxidation. Successful extension of the route allowed preparation of neocaesalpin AA (2) as well as nominal neocaesalpin K (3) and suggested structural revision of neocaesalpin K, leading to the hypothesis that the two are likely the same natural product with correct assignment as 2.",10.1002/anie.202310149,2023-09-08,0.5862848159133746
Synthesis,Stereoselective Total Synthesis of epi-Phomopsolide B,"The stereoselective total synthesis of epi -phomopsolide B, a polyhydroxy lactone natural product, has been accomplished. Starting from the commercially available diethyl l -tartrate, the synthesis­ involved an asymmetric Evans aldol approach and Still–Gennari olefination. Further, the resulting epi -phomopsolide B was screened for cytotoxicity and antimicrobial properties, and the outcome is presented.",10.1055/s-0034-1378565,2014-08-12,0.5862845050221186
Organic Letters,Total Synthesis of (−)-8-<i>O</i>-Methyltetrangomycin (MM 47755),"A stereoselective total synthesis of the natural antibiotic (-)-8-O-methyltetrangomycin 1 is reported. The essential steps for this convergent synthesis are the transformation of a geraniol epoxide into a chiral octadiyne derivative, which was converted into a triyne. The cobalt-mediated [2+2+2] cycloaddition of the triyne led to a benz[a]anthracene system, which was oxidized with Ag(Py)(2)MnO(4) to a benz[a]anthraquinone. Deprotection with aqueous HF in acetonitrile and photooxidation afforded the desired product (-)-1. [reaction: see text]",10.1021/ol060667b,2006-05-16,0.5862807558235018
European Journal of Organic Chemistry,Enantioselective Synthesis of the Ester Side Chain of Homoharringtonine,"Abstract Details of the synthesis of the methyl ester of the side chain of homoharringtonine, a natural product with antileukemic properties, are reported below. The key tactical element involved a Michael addition between the known chiral imine 4 and 2‐acetoxyacrylonitrile ( 5 ), furnishing the adduct (2 R ,1′ R )‐ 6 with a high degree of regio‐ and stereoselectivity. This adduct was then converted into the target compound ( R )‐ 2 by a linear sequence of ten chemical operations, in 6.0% overall yield. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2003)",10.1002/ejoc.200300111,2003-06-16,0.5862775191641582
Tetrahedron,The addition of benzocyclobutenylidene to benzene. A novel route to benz[a]azclene.,,10.1016/s0040-4039(01)94869-5,1978-01-01,0.5862719260039888
Journal of the American Chemical Society,Enantioselective Synthesis of Chiral Sulfones by Ir-Catalyzed Asymmetric Hydrogenation: A Facile Approach to the Preparation of Chiral Allylic and Homoallylic Compounds,"A highly efficient and enantioselective Ir-catalyzed hydrogenation of unsaturated sulfones was developed. Chiral cyclic and acyclic sulfones were produced in excellent enantioselectivities (up to 98% ee). Coupled with the Ramberg-Bäcklund rearrangement, this reaction offers a novel route to chiral allylic and homoallylic compounds in excellent enantioselectivities (up to 97% ee) and high yields (up to 94%).",10.1021/ja306731u,2012-07-26,0.5862677963687883
Synthesis,"An Improved Synthesis of 1,4-Disubstituted Adamantanes",,10.1055/s-1972-21884,1972-01-01,0.5862621717140724
European Journal of Organic Chemistry,Formal Synthesis of (+)‐ and (–)‐Ferruginine,"Abstract A formal synthesis of the naturally occurring (+)‐ferrugine and of its enantiomer starting from the commercially available tropinone is reported. The desymmetrization of tropinone was achieved through formation of diastereomeric unsaturated sulfoxides using the Andersen procedure. Introduction of the acetyl C(2) side chain was achieved by conjugate addition of lithiated ethyl vinyl ether to an unsaturated sulfone. N ‐Boc‐Norferruginine, an advanced intermediate for the synthesis of ferruginine, was prepared in six steps and 19 % overall yield. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2007)",10.1002/ejoc.200700427,2007-07-25,0.5862621201852901
Organic Letters,First Diastereoselective Chiral Synthesis of (−)-Securinine,[reaction: see text] A diastereoselective total synthesis of securinine in optically pure form was achieved by employing ring-closing metathesis of the corresponding dienyne compound as a key step.,10.1021/ol0361251,2003-12-09,0.5862523315754483
Organic Letters,Stereoselective Synthesis of 2-Deoxyglycosides: An Efficient Protocol for Alcohol Deoxygenation,"A robust deoxygenation of glycosides to α/β-2-deoxyglycosides is achieved via photocatalytic reductive benzoate cleavage. This operationally simple method features broad functional group tolerance, applying to diverse mono/disaccharide substrates in moderate yields, and is scalable to 5 mmol, offering a practical and efficient synthesis route.",10.1021/acs.orglett.5c04094,2025-11-04,0.5862506998240418
Organic Letters,Synthesis of a C-Nucleoside Phosphonate by Base-Promoted Epimerization,"The efficient synthesis of a [2'S] C-nucleoside phosphonate and its corresponding prodrug has been realized. A phosphonomethoxy group was stereoselectively introduced at the anomeric 5'-carbon atom through glycosylation of a benzoyl protected [5'R]-acetoxy-[2'R]-9-deazaadenine. An unexpected epimerization at the 2'-position of the sugar moiety occurred upon removal of the protecting groups, but this was further exploited as a key reaction for improved synthesis of the target compound.",10.1021/acs.orglett.8b00123,2018-02-01,0.5862453879575266
Tetrahedron,Stereoselective preparation of synthetic equivalents of 2-deoxy-2-amino- and 3-deoxy-3-aminotetroses from malic acid. Application to the synthesis of C18-D-ribo-phytosphingosine,,10.1016/s0040-4039(01)80606-7,1989-01-01,0.5862447448179553
Organic Letters,"Asymmetric Synthesis of New β,β-Difluorinated Cyclic Quaternary α-Amino Acid Derivatives","The synthesis of new beta,beta-difluorinated cyclic quaternary alpha-amino acid derivatives 1 in which a ring-closing metathesis reaction (RCM) constitutes the key step is described. The approach employs imidoyl chlorides 3 as fluorinated building blocks, and the overall process involves the stereoselective creation of a quaternary stereocenter. Complete selectivity was achieved when (R)-phenylglycinol methyl ether was used as chiral auxiliary, allowing for the preparation of new six-membered cyclic fluorinated alpha-amino acids as single enantiomers.",10.1021/ol061733c,2006-08-01,0.586243112887584
Synlett,Transannular Cyclization with Grignard Reagents: Facile Synthetic Routes to Oxaadamantane and Protoadamantane Derivatives,"A simple and efficient synthetic route to different adamantanoid derivatives such as disubstituted oxaadamantane derivatives, trisubstituted protoadamantane, and trisubstituted adamantane derivatives starting from same precursor, 7-exo-epoxymethylene[3.3.1]nonan-3-one, is described.",10.1055/s-2008-1032054,2008-02-01,0.586232846738828
Tetrahedron,"Synthesis of macrocyclic terpenoids by intramolecular cyclization IX. Total synthesis of (±)-obscuronatin and (±)-biflora-4,10(19),15-triene.",,10.1016/s0040-4039(01)81685-3,1984-01-01,0.5862326838207471
Tetrahedron,"Aluminium-mediated [4+1] cyclization reaction: novel synthesis of 2,2,5,5-tetramethylcyclopentanecarboxylic acid",,10.1016/s0040-4039(00)79485-8,1991-01-01,0.5862265334745688
Organic Process Research & Development,A Practical Synthesis of Highly Hindered Biphenyl-2-carboxylates via Nucleophilic Aromatic Substitution of <i>tert</i>-Butyl 2-Methoxybenzoates with Aryl Grignard Reagent,"The fluorenone derivative ( OPC-34165 ) has potent repairing and protecting activities for peripheral and central nervous system degeneration. A synthesis of the biphenyl-2-carboxylic acid derivative, which is the key intermediate of OPC-34165, is described employing the S N Ar reaction of tert -butyl 2-methoxybenzoate with aryl Grignard reagent in refluxing THF−toluene.",10.1021/op0001279,2001-06-28,0.5862264614003165
Synthesis,"Facile Synthesis of 3-Carbamoyl-1,2,4-Oxadiazoles","A range of 1,2,4-oxadiazoles, having a carbamoyl group at the 3-position, were synthesized from 2-methyl-4-nitroisoxazolin-5(2H)-one via three steps. Ammonolysis of this nitroisoxazol­one afforded 2-amino-2-hydroxyimino-N-methylacetamide in excellent yield. O-Acylation of this key amidoxime, followed by ring closure, proceeded smoothly to give 3-carbamoyl-1,2,4-oxadiazoles having a substituent at the 5-position which could be easily modified by changing the O-acylating agent. Since each step requires only simple manipulations, the synthetic utility of this procedure is concluded to be high.",10.1055/s-2006-950210,2006-10-01,0.5862247190128591
Synlett,Total Synthesis of (-)-Aristeromycin,"All articles of this category The carbocyclic analogue of adenosine, (-)-aristeromycin (2; 9-[1′ R ,2′ S ,3′ R ,4′ R )-2′, 3′-dihydroxy-4′-(hydroxymethyl)-1′-cyclopentyl]-9 H -purin-6-amine) is synthesized from inexpensive natural tartaric acid ( 3 ) via key intermediate 8 [(4 R , 5 S )-4,5-isopropylidenedioxy-3-methoxy-2-cyclopentenone]. The synthetic strategy allows the preparation of different 6-substituted analogues 17 of (-)-aristeromycin.",10.1055/s-1990-21238,1990-01-01,0.5862230208275145
European Journal of Organic Chemistry,"Synthesis of Benzo[b]phenanthridines and Related Naturally Occurring 2-Aryl-1,4-naphthoquinones by Palladium- and Copper-Catalyzed Coupling of Organostannanes with Bromoquinones","Syntheses of phenanthroviridone, gilvocarcin BE-12406X2, antibiotic WS 5995B, and a key intermediate for the synthesis of jadomycin are described, based on palladium- and copper-catalyzed coupling reactions of sterically hindered arylstannanes with 2-bromonaphthoquinones.",10.1002/1099-0690(200101)2001:1<163::aid-ejoc163>3.3.co;2-v,2001-01-01,0.5862171766429456
European Journal of Organic Chemistry,"Synthesis of Benzo[b]phenanthridines and Related Naturally Occurring 2-Aryl-1,4-naphthoquinones by Palladium- and Copper-Catalyzed Coupling of Organostannanes with Bromoquinones","Syntheses of phenanthroviridone, gilvocarcin BE-12406X2, antibiotic WS 5995B, and a key intermediate for the synthesis of jadomycin are described, based on palladium- and copper-catalyzed coupling reactions of sterically hindered arylstannanes with 2-bromonaphthoquinones.",10.1002/1099-0690(200101)2001:1<163::aid-ejoc163>3.0.co;2-3,2001-01-01,0.5862171766429456
Journal of the American Chemical Society,Redirecting the Cyclization Steps of Fungal Polyketide Synthase,"Regiospecific cyclizations of the nascent poly-beta-ketone backbones dictate the structures of polyketide natural products. The fungal iterative megasynthases use terminal thioesterase/claisen cyclase (TE/CLC) domains to direct the fate of the polyketide chains. In this work, we present two strategies toward redirecting the cyclization steps of fungal PKSs using the Gibberella fujikuroi PKS4. First, inactivation or removal of the TE/CLC domain resulted in the synthesis of the new polyketide SMA93 2. Complementation of the mutant PKS4 with a standalone TE/CLC domain restored the regioselective cyclization steps of PKS4 and led to the synthesis of SMA76 1, demonstrating that cyclization enzymes can interact with the megasynthase in trans. This led to the second approach in which various dissociated, bacterial tailoring enzymes were added to the megasynthase in trans. Addition of the act KR led to the synthesis of mutactin 3, while the addition of first ring and second ring cyclases yielded anthraquinone compounds DMAC 5 and SEK26 6. The cooperative activities of fungal and bacterial PKS components are especially important and enable synthesis of polyketides utilizing enzymes from two distinct families of PKSs.",10.1021/ja078091o,2007-12-12,0.5862142466016995
Angewandte Chemie International Edition,Conformational Locking through Allylic Strain as a Device for Stereocontrol—Total Synthesis of Grandisine A,"Controlled fusion: The use of a seco ring D precursor to control both the stereochemistry of a critical cycloaddition with acetaldehyde and the direction of protonation of the resultant silyl enol ether cycloadduct has led to the total synthesis of grandisine A, which shows promising selectivity for binding to the δ-opioid receptor. The D ring is installed in the final stages of the synthesis (see scheme, LA=Lewis acid).",10.1002/anie.200703245,2007-09-17,0.5862109950571655
Synthesis,"Asymmetric Synthesis; XXXVII: Synthesis of 2,6-Disubstituted Piperazines from Chiral Non-Racemic Lactams","All articles of this category General and convenient syntheses of optically active 2,6-disubstituted piperazines are described. The method is based on diastereoselective alkylation of lactam 8 derived from ( R )-(-)-phenylglycinol followed by a regio- and diastereoselective functionalisation of carbamates 10c and 10d . This procedure allowed the preparation of new α -amino acids 15 and 16 . asymmetric synthesis - ( R )-(-)-phenylglycinol - 2,6-disubstituted piperazine - metalation of carbamate - α -amino acid",10.1055/s-1996-4299,1996-07-01,0.5862085566914729
Synthesis,Phenazines and Natural Products; Novel Synthesis of Saphenic Acid,"The natural product saphenic acid (6-(1-hydroxyethyl)1- phenazinecarboxylic acid) was synthesized from readily accessible starting materials. The desired product was obtained in an overall yield of 22% for four steps with the key steps being formation of a diphenylamine, followed by cyclization under alkaline and reducing conditions. Assignments of <sup>1</sup>H NMR spectra were achieved by homo- and heteronuclear 1D and 2D correlations. Double pulsed field gradient spin-echo one-dimensional NOESY proved especially valuable for assignment of aromatic protons.",10.1055/s-1999-3587,1999-10-01,0.586208236874072
Synthesis,An Improved Synthesis of ω-(5-Nitro-2-furyl)-polyenoic Acid Derivatives,,10.1055/s-1972-21842,1972-01-01,0.5862060854060488
Tetrahedron,8-endo Cyclization of (alkoxycarbonyl)methyl radicals: Stereoselective synthesis of (−)-clavukerin A and (−)-11-hydroxyguaiene,,10.1016/0040-4039(96)01279-8,1996-08-01,0.5862044189094147
Tetrahedron,"A chemoselective, acid mediated conversion of amide acetal to oxazole: The key step in the synthesis of cardiovascular drug, ifetroban sodium",,10.1016/s0040-4039(98)00904-6,1998-07-01,0.5862015260694043
Organic Letters,Reaction of 2-Bromomethylazoles and TosMIC:  A Domino Process to Azolopyrimidines. Synthesis of Core Tricycle of the Variolins Alkaloids,"A new reaction of N-protected 2-bromomethylazoles and tosylmethyl isocyanide (TosMIC) leading to the preparation of azolopyrimidines is described. This domino sequence was used to synthesize the pyrido[3',2':4,5]pyrrolo[1,2-c]pyrimidine core of alkaloids variolins from 4-methoxy-2-methylpyrrolo[2,3-b]pyrimidine in two steps.",10.1021/ol0062087,2000-09-26,0.5862006393408342
Journal of Organic Chemistry,Novel “Protecting Group-Dependent” Alkylation−RCM Strategy to Medium-Sized Oxacycles:  First Total Synthesis of (−)-Isoprelaurefucin,"[reaction: see text] A novel ""protecting group-dependent"" alkylation strategy was developed for complementary diastereoselective syntheses of alpha,alpha'-syn- and alpha,alpha'-anti-bis-alkenes 2 and 3, which represent ring-closing metathesis (RCM) substrates for medium-sized oxacycles. This principle has been applied to a stereoselective and concise total synthesis of (-)-isoprelaurefucin (4) in 14 steps in 12% overall yield from known epoxide 8.",10.1021/jo050974f,2005-09-30,0.586199788153829
Synthesis,An Efficient Synthesis of (4<i>S</i>)-(-)-4-Isopropyl-2-oxazolidinone,"All articles of this category A new, efficient, cost-effective method for the preparation of the Evans' chiral auxiliary (4 S )-4-isopropyl-2-oxazolidinone ( 4 ) is described. A Schotten-Baumann acylation of valine with phenyl carbonochloridate quantitatively affords the protected valine, which is then reduced with borane in tetrahydrofuran to give an alcohol. Cyclization with a catalytic amount, of potassium tert -butoxide gives 4 in 81% overall yield and in 41-43% after crystallization from ethyl acetate/ n -hexane.",10.1055/s-1989-27337,1989-01-01,0.5861925020659182
Tetrahedron,Chiron approach towards a potent toxin fumonisin B1 backbone: Synthesis of its hexaacetate derivative,,10.1016/s0040-4039(98)00588-7,1998-05-01,0.5861919587278445
Tetrahedron,A new synthesis of cyclopenta [a] phenanthrene and its carcinogenic derivatives,,10.1016/0040-4039(88)85123-2,1988-01-01,0.5861904515712615
Tetrahedron,"1,2-Dialkoxycarbonylhydrazine derivatives of pyrroles and indolizines. A new synthesis of cycl[3.2.2]azines",,10.1016/s0040-4039(00)78741-7,1980-01-01,0.5861904515712615
Tetrahedron,A new synthon for the synthesis of aminoinositol derivatives,,10.1016/j.tetlet.2017.05.099,2017-06-02,0.5861904515712615
Tetrahedron,New synthesis of quinazoline and benzoquinazoline derivatives,,10.1016/s0040-4039(00)88339-2,1983-01-01,0.5861904515712615
Tetrahedron,"The synthesis of new 3,4-dimethylenethiolane derivatives",,10.1016/s0040-4039(01)81089-3,1987-01-01,0.5861904515712615
Synthesis,Derivatives of 4-Azahomoadamantane: a New Synthesis by Photochemistry,,10.1055/s-1974-23441,1974-01-01,0.5861904515712615
Tetrahedron,A new synthesis of 4-oxygenated β-carboline derivatives by Fischer indolization,,10.1016/j.tetlet.2005.03.177,2005-04-16,0.5861904515712615
Journal of Organic Chemistry,Efficient Two-Step Synthesis of 9-Aryl-6-hydroxy-3<i>H</i>-xanthen-3-one Fluorophores,[reaction: see text] A two-step method for the synthesis of 9-aryl-6-hydroxy-3H-xanthen-3-one fluorophores involving condensation of aryl aldehydes and fluororesorcinol is shown to proceed through a triarylmethane intermediate. The condensation is complicated by retro-Friedel-Crafts reactions which can be minimized by controlling the amount of acid. The xanthenone ring system is prepared by a final oxidative cyclization with DDQ.,10.1021/jo051243i,2005-10-01,0.5861862904104997
Organic Process Research & Development,Application of Oxathiazolidine-S-oxide Chemistry to the Large-Scale Single-Step Synthesis of an O-Arylethanolamine,"Alternative routes to the arylethanolamine subunit of a development drug have been investigated. The selected route, involving O-alkylation of a phenol using N-benzyloxathiazolidine-S-oxide, was developed to give a process used successfully for pilot plant manufacture.",10.1021/op9800865,1999-06-11,0.5861857627796969
Journal of Organic Chemistry,"Total Synthesis of 7-Deoxy-6-<i>O</i>-methylfusarentin Featuring a Chelation-Controlled 1,3-Reetz–Keck-Type Allylation","The total synthesis of 7-deoxy-6-O-methylfusarentin (1) and a formal synthesis of 7-deoxy-6,8-O-dimethylfusarentin (2) has been successfully achieved in 10 steps. The described tactic underscores a diastereoselective strategy which incorporates a single acyclic reaction based on the initial stereocenter by means of a 1,3-chelation-controlled Reetz-Keck-type allylation.",10.1021/jo301167a,2012-08-13,0.5861848893027661
European Journal of Organic Chemistry,Synthesis of Amino‐Bridged Oligosaccharide Mimetics,"Abstract Synthesis of amino‐bridged oligosaccharides using reductive amination opens rapid access to novel glycomimetic target structures as potential ligands for the receptor protein NKR P1 of natural killer cells. Emphasis was laid on fast and facile synthetic routes. The carbonyl building blocks were easily obtained by oxidation with Dess–Martin periodinane or iodoxybenzoic acid (IBX). For the required amino‐functionalized units, reduction of azide precursors was advantageous, and generation of the novel oligosaccharides was achieved by subsequent reductive amination. The target saccharide structures feature a bridging nitrogen atom inserted between two non‐anomeric positions as well as including one anomeric position.",10.1002/ejoc.200901106,2009-12-22,0.5861811006540215
Journal of Organic Chemistry,Synthesis of (2<i>S</i>)-2-Chloro-2-fluororibolactone via Stereoselective Electrophilic Fluorination,A novel and efficient route for the preparation of (2S)-2-chloro-2-fluorolactone 29 is described. This approach takes advantage of a highly efficient diastereoselective electrophilic fluorination reaction (94% yield; >50:1 dr).,10.1021/acs.joc.7b02245,2017-11-15,0.586178679173566
Angewandte Chemie International Edition,Total Synthesis of (−)‐Dactylolide,"Multiple metals in action: Relying on the prowess of various metal-catalyzed CO and CC bond-forming reactions, a concise asymmetric total synthesis of (−)-dactylolide has been achieved (see scheme). The formation of a Z-trisubstituted vinylboronate through an Alder–ene reaction and subsequent rhenium-mediated regioselective transposition of an allylic alcohol are the key features of this convergent synthesis.",10.1002/anie.201001681,2010-05-10,0.5861768885203572
Synthesis,"One-Pot, Two-Step Synthesis of Highly Functionalized 4-Indolyl/Pyrrolyl-Chromanes via a para-Quinone Methide Formation–1,8-Addition Sequence","Abstract An efficient one-pot, two-step synthesis of structurally diverse 4-indolyl-/pyrrolyl-chromanes was developed starting from o-propargylated salicylaldehydes, 2,6-dialkylphenols and indoles/pyrrole. This process begins with a sequential secondary amine-catalyzed formation of p-quinone methides followed by Brønsted acid catalyzed 1,8-addition with indoles/pyrrole to access the functionalized chromanes in high yields (up to 91%). This sequential reaction generates three new C–C bonds, shows high step- and atom-economy with only one molecule of water as the side product and gives access to complex molecular frameworks without the need for the isolation of the intermediates.",10.1055/a-2371-3579,2024-07-23,0.5861752237198399
European Journal of Organic Chemistry,Synthesis of New Trisubstituted 4‐Aminopiperidines as PAF‐Receptor Antagonists,"Abstract Two novel classes of 4‐aminopiperidines substituted in the 3‐position by groups bearing either a carbamate or a ureido function have been synthesized from ethyl 4‐oxo‐3‐piperidinecarboxylate and 3,3′‐iminobis(propanenitrile), respectively. The key step in this synthesis, the reduction of the piperidinic β‐enamino ester or nitrile, occurred readily. In contrast to published works, the free primary amines could be isolated from the corresponding β‐amino ester or nitrile. Regioselective amidification of the amino group offered two pairs of diastereoisomers which were successfully separated and identified. Measurement of PAF‐receptor antagonist activity gave interesting results with an IC 50 close to the micromolar.(© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2008)",10.1002/ejoc.200700667,2007-11-12,0.5861751959506974
Synthesis,Safe and Efficient Continuous-Flow Synthesis and Batchwise Hydrolysis of Ethyl 5-Acetyl-1H-pyrazole-3-carboxylate: A Key Synthon of Darolutamide,"Abstract A safe and metal-free process using ethyl glycinate hydrochloride as the starting material has been developed for the preparation of ethyl 5-acetyl-1H-pyrazole-3-carboxylate, a key intermediate for the synthesis of potential blockbuster drug substance darolutamide. In the key step, the toxic and explosive intermediate, ethyl diazoacetate was generated and used in situ. Reaction parameters were optimized for both the batchwise and the continuous-flow variant of the synthesis. In the next step, alkaline hydrolysis of the ester led to 5-acetyl-1H-pyrazole-3-carboxylic acid, which can not only be used as a darolutamide intermediate, but it can also be considered as a valuable building block for other types of organic and medicinal chemistry transformations.",10.1055/s-0042-1751389,2022-11-23,0.5861703103203786
Organic Letters,Total Synthesis of (+)-Psymberin (Irciniastatin A): Catalytic Reagent Control as the Strategic Cornerstone,"An effective total synthesis of the marine sponge cytotoxin (+)-psymberin [irciniastatin A (1)] has been achieved. Highlights of the strategy include a Diels-Alder reaction between a bis-siloxy diene and an allene to construct the aromatic ring, a boron-mediated aldol reaction to elaborate the C(15-17) all syn stereotriad, catalytic reagent control to set the C(8, 9, 11 and 13) stereogenic centers of the tetrahydropyran core, and a late-stage Curtius rearrangement to install the sensitive N,O-aminal moiety. The synthesis proceeds with a longest linear sequence of 21 steps from commercially available 2,2-dimethyl-1,3-propanediol.",10.1021/ol802466t,2008-12-11,0.5861641344579565
Organic Letters,"Concise, Enantioselective Total Synthesis of (−)-Alstonerine",A novel enantioselective total synthesis of (-)-alstonerine has been completed that requires only 15 steps from L-tryptophan. The synthesis features the first application of a Pauson-Khand reaction to synthesize an azabridged bicyclic skeleton. [reaction: see text],10.1021/ol0700761,2007-02-14,0.5861619824147548
Synlett,Synthesis of Hydroxy-α-sanshool,"The amide hydroxy-α-sanshool is responsible for the mild numbing sensation experienced when Sichuan (or Szechuan) peppercorns ( huajiao ) are eaten. It has been synthesized in six steps from simple commercially available starting materials using Wittig reactions as the key transformations for construction of the carbon skeleton. The penultimate synthetic intermediate was 2 E ,6 Z ,8 E ,10 E -dodecatetraenoic acid, and its crystalline nature allowed it, and thus hydroxy-α-sanshool, to be purified to a very high level of stereochemical homogeneity.",10.1055/s-0032-1317172,2012-09-13,0.5861614371574533
Synthesis,"Efficient Synthesis of Substituted Pyranoquinolinones from 2,4-Dihydroxyquinoline: Total Synthesis of Zanthosimuline, <b><i>cis</i></b>-3<b>′</b>,4<b>′</b>-Dihydroxy-3<b>′</b>,4<b>′</b>-dihydroflindersine, and Orixalone D","A convenient and efficient synthesis of pyranoquinoli­nones was achieved using the ethylenediamine diacetate catalyzed reactions of 2,4-dihydroxyquinoline and a variety of α,β-unsaturated aldehydes in good yield. The key feature of these reactions is the formal [3+3] cycloaddition. This new methodology was applied successfully to the total synthesis of naturally occurring pyranoquinolinone alkaloids, zanthosimuline, cis-3′,4′-dihydroxy-3′,4′-dihydroflindersine, and orixalone D.",10.1055/s-2007-983893,2007-09-24,0.5861606807028141
Tetrahedron,"Novel, regioselective transformation of an oxirane system. An efficient approach to the synthesis of endocannabinoid 2-arachidonoylglycerol",,10.1016/s0040-4039(02)00116-8,2002-02-01,0.5861597098028829
European Journal of Organic Chemistry,"Biomimetic Total Syntheses of Amorfrutins A, B, (<i>S</i>)‐D and (<i>R</i>)‐D and Formal Synthesis of Amorfrutin C","Abstract Bibenzyl natural products, such as the amorfrutins, contain a heavily substituted aromatic core and display a diverse range of biological activities (anti‐tumor, anti‐diabetic, antimicrobial, and antibiotic). In this study, we report unified syntheses of amorfrutin A to D either through total or formal synthesis by employing a dual biomimetic strategy of polyketide aromatization followed by remote terpene functionalization. The key core structures were synthesized from β‐keto dioxinone esters through a magnesium(II) mediated regioselective C‐acylation, palladium catalyzed decarboxylative allylic rearrangement, and dehydrative cyclization.",10.1002/ejoc.202100301,2021-05-06,0.5861505581552462
Tetrahedron,Ethyl 5-substituted-3-isoxazolecarboxylates as starting materials for a convenient route to 3(2H)furanones and 3(2H)iminofuranes.,,10.1016/s0040-4039(01)81426-x,1984-01-01,0.5861498025235786
European Journal of Organic Chemistry,Asymmetric Synthesis of (<i>S</i>)‐(−)‐Acromelobic Acid,"Abstract ( S )‐(−)‐Acromelobic acid ( 1 ) was synthesized in nine steps in enantiomerically pure form from citrazinic acid ( 4 ) in an overall yield of 21%. The key steps of this synthesis are the introduction of the amino function by the bis(lactim) ether method and the introduction of the acid function by Stille coupling. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2003)",10.1002/ejoc.200300059,2003-11-01,0.5861469978075919
Organic Letters,Correction to “Stereodivergent Total Synthesis of Ethyl Plakortide Z”,,10.1021/acs.orglett.5c04106,2025-11-27,0.5861401875031652
Journal of Organic Chemistry,Synthesis of SGLT2 Inhibitors by Means of Fukuyama Coupling Reaction,"Disclosed herein is a novel and efficient synthesis of dapagliflozin and canagliflozin, the most advanced sodium glucose cotransporter 2 inhibitors (SGLT2 inhibitors), for the treatment of type 2 diabetes mellitus (T2DM). Per Ac-protected thioester was prepared by the treatment of per Ac d -gluconolactone with 1-dodecanethiol and i PrMgCl without affecting labile Ac-protecting groups. Aryl bromide (ArBr) was synthesized through reduction of diaryl ketone to diaryl methane by the TiCl 4 /NaBH 4 /DME-MeOH reduction system. Fukuyama coupling of the thioester with aryl zinc reagent prepared from ArBr gave a multifunctional aryl ketone at 40 °C in a high yield where the use of a limited amount of a mixed solvent (7.2 volumes (v), THF:toluene:DMF = 3v/4v/0.2v) was crucial to achieve the higher yield. After cleavage of the THP group, hydroxy ketone obtained was treated with methanesulfonic acid (MSA) in MeOH to give a methoxy-cyclized product in a single step and in a quantitative yield, which was allowed to silane reduction to furnish dapagliflozin in an excellent yield. By following the same procedure, canagliflozin was synthesized. The current synthetic method is featured by high yields, mild reaction conditions, and the use of inexpensive reagents and readily cleavable protecting groups.",10.1021/acs.joc.3c01873,2023-10-20,0.5861373597916766
Journal of Organic Chemistry,"Synthesis of a Conjugation-Ready, Phosphorylated, Tetrasaccharide Fragment of the O-PS of <i>Vibrio cholerae</i> O139","A new pathway to the tetrasaccharide α-Colp-(1→2)-4,6-P-β-d-Galp-(1→3)-[α-Colp-(1→4)]-β-d-GlcpNAc-1-(OCH2CH2)3NH2 has been developed. Glycosylation of 8-azido-3,6-dioxaoctyl 4,6-O-benzylidene-2-deoxy-2-trichloroacetamido-β-d-glucopyranoside with 3,4,6-tri-O-acetyl-2-O-bromoacetyl-α-d-galactopyranosyl bromide afforded the β-linked disaccharide. Debromoacetylation followed by reductive opening of the benzylidene acetal afforded the disaccharide diol acceptor. Halide-assisted glycosylation with 2,4-di-O-benzyl-α-colitosyl bromide gave the 1,2-cis-coupling product. Deacetylation followed by regioselective phosphorylation gave isomeric (R,S)-(P)-4(II),6(II)-cyclic phosphates, which were globally deprotected by one-step catalytic (Pd/C) hydrogenation/hydrogenolysis. The target tetrasaccharide, obtained in high overall yield, is amenable for conjugation to proteins.",10.1021/acs.joc.5b02105,2015-11-03,0.5861349377228318
Tetrahedron,Simple approach to the synthesis of novel tricyclic BACE1 inhibitor warhead through β-lactam opening,,10.1016/j.tetlet.2015.05.017,2015-05-11,0.5861326165585192
Organic Letters,Total Synthesis of Beshanzuenone D and Its Epimers and Abiespiroside A,"A unified and protecting-group-free six-step total synthesis of bisabolane-type sesquiterpenoid beshanzuenone D and its stereoisomers and abiespiroside A using S -(+)-carvone as a common chiral-pool building block is disclosed. This synthetic route features chemoselective allylic chlorination of carvone, Au(I)-catalyzed cycloisomerization induced construction of furan from homopropargylic diol, substrate-controlled selective hydroxylation using Davis-oxaziridine, and dye-sensitized photo-oxidation (through 1 O 2 ) of hydroxyalkyl tethered furan to access oxaspirolactone as key transformations. A comprehensive set of NMR data along with DFT calculations, ECD spectra, and optical rotation measurements of the synthesized beshanzuenone D and its epimers were obtained to confirm absolute configurations.",10.1021/acs.orglett.0c03157,2020-10-26,0.5861308862069022
Organic Letters,Total Synthesis of Brevetoxin A,"A total synthesis of brevetoxin A is reported. Two tetracyclic coupling partners, prepared from previously reported advanced fragments, were effectively united via a Horner-Wittig olefination. The resulting octacycle was progressed to substrates that were explored for reductive etherification, the success of which led to a penultimate tetraol intermediate. The tetraol was converted to the natural product through an expeditious selective oxidative process followed by methylenation.",10.1021/ol802710u,2008-12-19,0.5861243138370864
Synlett,A Concise Total Synthesis of (±)-Mesembrine,A concise total synthesis of (±)-mesembrine has been successfully accomplished in seven steps and 24% overall yield from commercially available 3-ethoxy-2-cyclohexen-1-one. Central to the assembly of the skeleton of mesembrine are a Johnson–Claisen rearrangement for the formation of the benzylic quaternary stereocenter and direct allylic oxidation to generate the substrate for the amidation/transannular aza-conjugate addition reaction.,10.1055/s-0036-1591547,2018-02-16,0.5861235558537703
Synlett,Stereoselective Formal Synthesis of Crocacin C via Prins Cyclization,A formal synthesis of crocacin C is described proving the versatility of Prins cyclization in natural product synthesis. The ­approach is convergent and highly stereoselective. Cross-metathesis and Heck reactions were utilized for the insertion of an aromatic group in a stereocontrolled manner.,10.1055/s-2007-984896,2007-07-12,0.5861213693387013
Synlett,A Practical Preparation of Imatinib Base,"A practical preparation of imatinib base was reported in this article. Compared with reported works, the features of this work were the concise procedures, the industrially available starting materials, the avoidance of expensive or highly toxic transition-metal catalysts or reagents, and the genotoxic impurities 6-methyl- N 1 -[4-(pyridin-3-yl)pyrimidin-2-yl]benzene-1,3-diamine and 4-(chloromethyl)- N -(4-methyl-3-{[4-(pyridin-3-yl)pyrimidin-2-yl]amino}phenyl)benzamide. The method was scalable to at least 100 mmol, and the products were separated by simple recrystallizations.",10.1055/s-0035-1562498,2016-06-23,0.5861121906373123
Tetrahedron,"Diastereoselective synthesis of 3-amino-1,2-diols by reductive alkylation of 2,3-dialkoxynitriles",,10.1016/s0040-4039(00)00202-1,2000-04-01,0.5861116975261522
Tetrahedron,Enantioselective synthesis of (R)-phenylephrine hydrochloride,,10.1016/s0040-4039(03)01554-5,2003-08-01,0.5861108360175549
Organic Process Research & Development,Large Scale Synthesis of an Ampakine-type Active Pharmaceutical Ingredient Based on a Telescoped Regioselective Double Amidation Reaction,"This work describes the process development and manufacture of an ampakine-type active pharmaceutical ingredient in clinical trials. A regioselective CDI-mediated amidation process was optimized for the subsequent couplings of two distinctive amines with a terephthalic acid substrate. Choice of the synthetic route, key scale-up issues, safety calorimetry, and optimization of all steps for multikilogram production are discussed.",10.1021/acs.oprd.9b00241,2019-07-11,0.5861081850952142
Organic Process Research & Development,"Large-Scale Asymmetric Synthesis of the 3,6,7,8-Tetrahydrochromeno[7,8-<i>d</i>]imidazole BYK 405879: A Promising Candidate for the Treatment of Acid-Related Diseases","A process for the synthesis of the potassium-competitive acid blocker BYK 405879 ( 8 ) was established based on the approach used in medicinal chemistry (asymmetric hydrogenation of prochiral ketone 15 and Mitsunobu cyclization of the resulting alcohol 34 ). Several critical reaction steps were optimized. The synthesis of prochiral ketones was accomplished using ethyl 3-(2-methylphenyl)-3-oxopropanoate instead of 1-[1-(2-methylphenyl)vinyl]pyrrolidine, a reagent that was difficult to prepare and possesses limited shelf life. The catalyst loading of the asymmetric hydrogenation step was reduced significantly from a S/C ratio of 100:1 to a S/C ratio of 2500:1 by benzyl protection of ketone 15 . After the Mitsunobu cyclization, the removal of byproduct was easily accomplished through acid−base extraction, and pure BYK 405879 ( 8 ) was then obtained by means of crystallization in the presence of succinic acid.",10.1021/op800177x,2008-09-25,0.5861035259661104
Synlett,Synthetic Studies toward Tubiferal A: Asymmetric Synthesis of a Model ABC-Ring Compound,"Abstract Synthetic studies on an ABC-ring model of tubiferal A, a triterpenoid isolated from the fruit bodies of the Tubifera dimorphotheca myxomycete, are described. The stereogenic centers at the angular positions were constructed through the stereoselective addition of a C-ring allylborane followed by an Eschenmoser–Claisen rearrangement reaction prior to the formation of the AB-ring system by a double intramolecular alkylation reaction of a dichloro nitrile intermediate.",10.1055/a-1697-7477,2021-11-16,0.5861034350835735
Synlett,"Synthesis of (1<i>S</i>,3<i>R</i>,5<i>R</i>,7<i>S</i>)-Sordidin,the Main Component of the Aggregation Pheromone of the Banana Weevil <i>Cosmopolites sordidus</i>","A synthesis of the banana weevil pheromone component (1S,3R,5R,7S)-sordidin starting from (S)-2-(2-ethyl-1,3-dioxolanyl)propan-1-ol and (R)-4-hydroxypentan-2-one is described. No epimerization was observed for the final, intramolecular, acid-catalyzed cyclization step using aqueous oxalic acid.",10.1055/s-0028-1087373,2008-12-12,0.5860998630863093
Organic Letters,The Rearrangement Route to 3-CH<sub>2</sub>X-2-azabicyclo[2.1.1]hexanes. Substituent Control of Neighboring Group Participation,The stereocontrolled synthesis of a functionalized 3-hydroxymethyl-2-azabicyclo[2.1.1]hexane synthon for a variety of methano-bridged pyrrolidines has been effected. The key step in an electrophilic addition-rearrangement route uses a 3-nosyloxymethyl group in the 2-azabicyclo[2.2.0]hex-5-ene precursor in order to suppress unwanted competitive oxygen neighboring group participation. [reaction: see text],10.1021/ol020007g,2002-03-22,0.5860983046145251
Journal of Organic Chemistry,Asymmetric Total Synthesis of Cryptorigidifoliol I,"An efficient asymmetric total synthesis of cryptorigidifoliol I based on an unusual Luche reduction leading to bicyclic etherification and acid hydrolysis to a thermodynamically less stable 4-hydroxy-2,6- trans -disubstituted-THP moiety has been achieved. The easy setup of trans -2,6-substitution on the core pyran ring through bicyclic etherification would enable the synthesis of various THP and bicyclic-THP-lactone natural products.",10.1021/acs.joc.4c00259,2024-03-14,0.5860899959025107
European Journal of Organic Chemistry,"Total Syntheses of Eudistomins Y<sub>1</sub>–Y<sub>7</sub> by an Efficient One‐Pot Process of Tandem Benzylic Oxidation and Aromatization of 1‐Benzyl‐3,4‐dihydro‐β‐Carbolines","Abstract The first total synthesis of eudistomin Y 7 ( 7 ) and total syntheses of eudistomins Y 1 –Y 6 ( 1 – 6 ) are described. An efficient room‐temperature conversion of 1‐benzyl‐3,4‐dihydro‐β‐carbolines ( 11 ) into 1‐benzoyl‐β‐carbolines ( 14 ) by a one‐pot process of tandem benzylic oxidation and aromatization as the key step of these total syntheses was also studied in detail.",10.1002/ejoc.201300080,2013-04-05,0.58608500995369
Tetrahedron,A concise synthesis of 4′-O-methyl honokiol,,10.1016/j.tetlet.2011.03.031,2011-03-16,0.586084245617275
Synlett,Synthesis of Trisubstituted Pyrimidines by Regioselective S<sub>N</sub>Ar and Suzuki Reactions of Polyhalopyrimidines,"An efficient, regioselective approach to the synthesis of trisubstituted pyrimidines was developed. Sequential functionalisation of commercially available polyhalopyrimidines provided the target compounds in moderate to good overall yields.",10.1055/s-2006-939050,2006-03-14,0.5860823158076235
Journal of Organic Chemistry,Synthesis of Unsaturated Polyazamacrolides from the Ladybird Beetle <i>Subcoccinella </i><i>v</i><i>igintiquatuorpunctata</i>,"The pupal defensive secretion of the ladybird beetle Subcoccinella vigintiquatuorpunctata consists of a mixture of macrocyclic polyamines (polyazamacrolides, PAMLs) dominated by three dimeric, 30-membered bislactones (1, 2, and 3), which represent the three possible head-to-tail combinations of the two building blocks (S)-(Z)-11-(2-hydroxyethylamino)-5-tetradecenoic acid (4) and (S)-(5Z,8Z)-11-(2-hydroxyethylamino)-5,8-tetradecadienoic acid (5). We now report the synthesis of these three alkaloids via a route involving the nucleophilic opening of a chiral aziridine as a common step.",10.1021/jo001200w,2001-01-09,0.5860818057403553
Tetrahedron,A novel route to the anti-HIV nucleoside d4T,,10.1016/0040-4039(95)00374-l,1995-04-01,0.5860785639805829
Tetrahedron,"Reaction of Schiff bases anions with α,ω-dihaloalkanes: Synthetic route to cyclic α-aminoacid derivatives.",,10.1016/s0040-4039(00)84346-4,1986-01-01,0.586077920344461
Journal of Organic Chemistry,Nitrile Biotransformations for Highly Enantioselective Synthesis of Oxiranecarboxamides with Tertiary and Quaternary Stereocenters; Efficient Chemoenzymatic Approaches to Enantiopure α-Methylated Serine and Isoserine Derivatives,"[reaction: see text] Biotransformations of a number of differently substituted and configured oxiranecarbonitriles using Rhodococcus sp. AJ270, a microbial whole-cell catalyst that contains nitrile hydratase/amidase, were studied. While almost all trans-configured 3-aryl-2-methyloxiranecarbonitriles and 2,3-dimethyl-3-phenyloxiranecarbonitrile were efficiently hydrated by the action of the less enantioselective nitrile hydratase, the amidase exhibited excellent 2S,3R-enantioselectivity against 2-methyl-3-(para-substituted-phenyl)oxiranecarboxamides. Under very mild conditions, biotransformations of nitriles provided an efficient and practical synthesis of 2R,3S-(-)-3-aryl-2-methyloxiranecarboxamides, electrophilic epoxides with tertiary and quaternary stereocenters, in excellent yield with enantiomeric excess greater than 99.5%. The synthetic applications of the resulting enantiomerically pure epoxides were demonstrated by convenient and straightforward syntheses of polyfunctionalized chiral molecules possessing a quaternary stereocenter such as R-(+)-2-hydroxy-2-methyl-3-phenylpropionic acid, 2R,3R-(-)-3-amino-2-hydroxy-2-methyl-3-phenylpropionic acid, and 2S,3S-(+)-2-amino-3-hydroxy-2-methyl-3-phenylpropionic acid, employing the regio- and stereospecific epoxide ring opening reactions of 2R,3S-(-)-2-methyl-3-phenyloxiranecarboxamide as the key steps.",10.1021/jo0482615,2005-03-02,0.586077556576522
Angewandte Chemie International Edition,Design and Synthesis of Chiral Oxathiozinone Scaffolds: Efficient Synthesis of Hindered Enantiopure Sulfinamides and Sulfinyl Ketimines,"Is that SO? The title scaffolds have a highly active and properly differentiated SO bond for the efficient synthesis of enantiopure sulfinamides. The method is practical, green, and has the potential to provide an economical commercial process for the synthesis of bulky sulfinamides.",10.1002/anie.201301676,2013-05-15,0.5860763949377417
Synlett,Synthetic Studies on the Viridin Skeleton through Regio- and Stereoselective Functionalization of the AE-Ring Moiety,"Abstract 4,5,6,7-Tetrahydroisobenzofurans, corresponding to the AC(D)E ring structure of viridin and equipped with required substituents on the A-ring, were synthesized with high regio- and stereoselectivities via the Diels–Alder adduct of a furan derivative and maleic anhydride. The key steps of this work include the regioselective opening of a tetrahydrofuran ring, a stereoselective epoxidation, and an AlMe3-mediated regioselective epoxide opening followed by stereoselective C-methylation.",10.1055/a-1527-3781,2021-06-11,0.5860649746627049
Tetrahedron,Highly chemoselective palladium-catalyzed Sonogashira coupling of 5-iodouridine-5′-triphosphates with propargylamine: a new efficient method for the synthesis of 5-aminopropargyl-uridine-5′-triphosphates,,10.1016/j.tetlet.2012.04.023,2012-04-13,0.5860604975892079
Organic Letters,"Stereodivergent Synthesis of Enantioenriched 2-Pyrrolidones via Diastereoselective Hydrogenation of α,β-Unsaturated γ-Lactams","Synthesis of optically enriched racetam analogues was achieved via highly remote diastereocontrolled and enantiocontrolled Pd/C-catalyzed hydrogenation of α,β -unsaturated γ-lactams. Various mono- and disubstituted 2-pyrrolidones were obtained in excellent yields and stereoselectivities, and a concise and large-scale synthesis of brivaracetam was developed from inexpensive l -2-aminobutyric acid. Surprisingly, stereodivergent hydrogenation was observed by modifying remote functionalized stereocenters and additives, which would provide alternative stereochemical options of chiral racetams synthesis.",10.1021/acs.orglett.3c00532,2023-03-31,0.5860502180510215
Journal of Organic Chemistry,An Enantioselective Synthesis of Voriconazole,"A new seven-step sequence to access voriconazole, a clinically used antifungal agent, was developed. The initial catalytic asymmetric cyanosilylation is the key to constructing the consecutive tetra- and trisubstituted stereogenic centers. The fluoropyrimidine unit frequently triggered unexpected side reactions, but careful amendment of the reaction sequence allowed for the concise enantioselective synthesis.",10.1021/jo4019528,2013-10-08,0.5860481578947535
Journal of the American Chemical Society,Modular Two-Step Route to Sulfondiimidamides,"Sulfur functional groups are common motifs in bioactive molecules. Sulfonamides are most prevalent but related aza-derivatives, in which oxygen atoms are replaced by imidic nitrogens, such as sulfoximines and sulfonimidamides, are gaining attraction. Despite this activity, the double aza-variants of sulfonamides, termed sulfondiimidamides, are almost completely absent from the literature. The reason for this is poor synthetic accessibility. Although a recent synthesis has established sulfondiimidamides as viable motifs, the length of the route and the capricious nature of the key sulfondiimidoyl fluoride intermediates mean that direct application to discovery chemistry is challenging. Herein, we describe a two-step synthesis of sulfondiimidamides, exploiting a hypervalent iodine-mediated amination as the key step. The starting materials are organometallic reagents, an unsymmetrical sulfurdiimide, and amines. The method allowed >40 examples to be prepared, including derivatives of three sulfonamide-based drugs. The operational simplicity, broad scope, and concise nature make this route attractive for discovery chemistry applications.",10.1021/jacs.2c04404,2022-06-22,0.5860451661716546
Tetrahedron,A new synthesis of unsymmetrical chalcogene substituted tetrachalcogene-fulvalenes.,,10.1016/0040-4039(91)85072-d,1991-06-01,0.586043553234634
Synthesis,A New Synthesis of 2-Substituted 1-Arylazoethenes,,10.1055/s-1977-24468,1977-01-01,0.586043553234634
Synthesis,1-Benzenesulfonyl-2-bromomethyl-3-phenylthioindole as a Synthon for 2-Substituted Indoles: A New Synthesis of 2-Aminomethylindoles,,10.1055/s-1983-30265,1983-01-01,0.586043553234634
Tetrahedron,A new entry towards the synthesis of 1-substituted 3-azetidinones,,10.1016/s0040-4039(01)00113-7,2001-03-01,0.586043553234634
Tetrahedron,A new synthesis of substituted α-methylene-γ-lactones,,10.1016/s0040-4039(01)86238-9,1979-01-01,0.586043553234634
Tetrahedron,Metallocenes from fulvenes : A new synthesis of functionally substituted ferrocenes,,10.1016/s0040-4039(01)94386-2,1972-01-01,0.586043553234634
Tetrahedron,"A new synthesis of the 2,2,3,5,6,6-substituted tetrahydropyran aplysiapyranoid A and its 5-epimer",,10.1016/s0040-4039(03)01468-0,2003-07-16,0.586043553234634
Synthesis,"A New Synthesis of 2,3,4-Substituted Quinolines",,10.1055/s-1978-24864,1978-01-01,0.586043553234634
Tetrahedron,A new 4-substituted-2-Cyclohexenone synthesis,,10.1016/s0040-4039(00)79311-7,1993-11-01,0.586043553234634
Organic Letters,Asymmetric Hydrogenation of Indazole-Containing Enamides Relevant to the Synthesis of Zavegepant Using Neutral and Cationic Cobalt Precatalysts,"The cobalt-catalyzed asymmetric hydrogenation of indazole-containing enamides relevant to the synthesis of the calcitonin gene-related peptide (CGRP) receptor antagonist, zavegepant ( 1 ), approved for the treatment of migraines, is described. Both neutral bis(phosphine)cobalt(II) and cationic bis(phosphine)cobalt(I) complexes served as efficient precatalysts for the enamide hydrogenation reactions, providing excellent yield and enantioselectivities (up to >99.9%) for a range of related substrates, though key reactivity differences were observed. Hydrogenation of indazole-containing enamide, methyl ( Z )-2-acetamido-3-(7-methyl-1 H -indazol-5-yl)acrylate, was performed on a 20 g scale.",10.1021/acs.orglett.3c01364,2023-06-04,0.5860415255751545
Tetrahedron,"The methyl ester of a new gibberellin, GA73: the principal antheridiogen.dta in",,10.1016/s0040-4039(00)80393-7,1988-01-01,0.586030706490333
Tetrahedron,Synthesis of WAY-163909; a selective 5-HT2CR agonist,,10.1016/j.tetlet.2022.154139,2022-09-13,0.586025848419648
Organic Letters,An Atom-Economical Method To Prepare Enantiopure Benzodiazepines with <i>N</i>-Carboxyanhydrides,"The development of a rapid, one-pot synthesis of diazepinones with simple reagents is described. N-Carboxyanhydrides (NCAs) are employed as amino acid building blocks that react with o-ketoanilines sequentially as electrophiles and nucleophiles to form diazepinones with water and carbon dioxide as byproducts. Notably, these reactions enable the coupling of stereodefined amino acid derived NCAs without racemization. This method is demonstrated by an improved synthesis of a key intermediate toward a bromodomain and extra-terminal (BET) bromodomain inihibitor.",10.1021/acs.orglett.7b00417,2017-03-08,0.5860254837175637
Tetrahedron,The total synthesis of (±)α- and (±)β-pinene: A general route to bicyclo[3.1.1]heptanes,,10.1016/s0040-4039(01)87310-x,1973-01-01,0.5860152174582867
Tetrahedron,"New strategy for racemization of 2-amino-1,3-propanediols, key intermediates for the synthesis of antibiotic drugs",,10.1016/s0040-4039(00)80813-8,1988-01-01,0.5860108397973983
Angewandte Chemie International Edition,10‐Step Asymmetric Total Synthesis and Stereochemical Elucidation of (+)‐Dragmacidin D,"The asymmetric synthesis of dragmacidin D (1) was completed in 10 steps. Its sole stereocenter was set by using direct asymmetric alkylation enabled by a C2-symmetric tetramine and lithium N-(trimethylsilyl)-tert-butylamide as the enolization reagent. A central Larock indole synthesis was employed in a convergent assembly of the heterocyclic subunits. The stereochemical evidence from this work strongly supports the predicted S configuration at the 6''' position, which is consistent with other members of the dragmacidin family of natural products.",10.1002/anie.201504113,2015-06-30,0.586006171011551
Tetrahedron,A new efficient synthesis of oseltamivir phosphate (Tamiflu) from (−)-shikimic acid,,10.1016/j.tetlet.2012.01.017,2012-01-25,0.5859961755432701
Tetrahedron,Toward a total synthesis of brassinosteroids; stereoselective generation of the hydrindane ring system,,10.1016/s0040-4039(02)00517-8,2002-04-01,0.5859961395835827
Chemical Science,Gram-scale synthesis of (+)-elacestrant streamlined by iridium-catalyzed dynamic kinetic asymmetric hydrogenation of α-substituted tetralones,"A catalytic protocol for the iridium-catalyzed dynamic kinetic resolution asymmetric hydrogenation (DKR-AH) of α-substituted tetralones to rapidly assemble various enantioenriched tetrahydronaphthols is disclosed. A wide range of enantioenriched tetrahydronaphthols were obtained in high yields and excellent stereoselectivities (up to 99% yield, up to >99.5 : 0.5 er and >20 : 1 dr). And this unique platform exhibited high efficiency for the enantioselective synthesis of (+)-elacestrant, which was approved by the FDA in 2023 for the treatment of metastatic breast cancer. Additionally, palladium-catalyzed amination of aryl chloride assisted in furnishing the gram-scale synthesis of this oral anti-tumor drug within 7 steps in 43% yield.",10.1039/d5sc05497d,2025-01-01,0.5859866732195704
Tetrahedron,"BF3·OEt2-catalyzed synthesis of 1-(tetrahydropyran-3-yl)-1,3-dihydroisobenzofuran and trans-fused hexahydropyrano[3,2-c]chromene derivatives",,10.1016/j.tetlet.2014.05.083,2014-05-29,0.5859809643397561
Journal of the American Chemical Society,A Stereodivergent Approach to (−)-α-Kainic Acid and (+)-α-Allokainic Acid Utilizing the Complementarity of Alkyne and Allene Cyclizations,"A formal synthesis of (+)-α-allokainic acid and a total synthesis of (−)-α-kainic acid were carried out using a short, efficient, and highly stereoselective approach. From an alkyne precursor, a nickel-catalyzed cyclization and a palladium-catalyzed rearrangement were utilized in the synthesis of (+)-α-allokainic acid. From an allene precursor, a nickel-catalyzed cyclization was utilized in the synthesis of (−)-α-kainic acid. The allene cyclization used in the latter sequence was the first example of a metal-catalyzed cyclization of this type.",10.1021/ja993069j,1999-11-17,0.585979620281638
European Journal of Organic Chemistry,Facile Synthesis of Cyclohexanediones and Dialkylresorcinols – Bioactive Natural Products from Entomopathogenic Bacteria,"Abstract A synthesis for the recently identified, widespread bacterial natural product classes of dialkylresorcinols and cyclohexanediones was developed. The synthesis route is similar to the biosynthesis route in that the formation of the cyclohexanedione ring results from two parts, as exemplified by the synthesis of the multifunctional isopropylstilbenes identified in Photorhabdus luminescens . Testing of these compounds revealed good bioactivity against Trypanosoma brucei rhodesiense and T. cruzi , the causative agents of sleeping sickness and Chagas disease, respectively.",10.1002/ejoc.201403346,2014-11-13,0.585972717296785
European Journal of Organic Chemistry,"A Copper‐Catalyzed One‐Pot, Three‐Component Diastereoselective Synthesis of 3‐Spiroazetidinimine‐2‐oxindoles and Their Synthetic Transformation into Fluorescent Conjugated Indolones","Abstract A facile and efficient copper(I)‐catalyzed one‐pot, three‐component diastereoselective synthesis that provides new 3‐spiroazetidinimine‐2‐oxindoles in excellent yield has been accomplished. The 3‐spiroazetidinimine‐2‐oxindoles underwent a facile ring‐opening reaction of the spiroazetidinimine unit by treatment with KOH/MeOH and p ‐thiocresol under basic conditions to afford two new classes of fluorescent conjugated indolones. This method has general applications with regard to the imines that are derived from 9‐fluorenone, 1,2‐diketones, and 1,2,3‐triketones.",10.1002/ejoc.201301244,2013-12-02,0.5859723294155791
European Journal of Organic Chemistry,A Flexible Synthetic Approach to Phosphatidylglycerols,"We report a 5‐step sequence for the synthesis of phosphatidylglycerols (PG) bearing different or identical chains at positions sn ‐1 and sn ‐2 starting from phenyl dichlorophosphate and using ( S )‐glycidol as the chiral source. Overall, this new approach is more convergent that the previously reported syntheses as the PG derivatives are constructed around the phosphorus center. Hence, this method is more convenient for the incorporation of expensive or complex acyl chains at the sn ‐2 position.",10.1002/ejoc.201701178,2017-11-21,0.5859672530010048
Organic Letters,"A Catalytic, Enantioselective Formal Synthesis of (+)-Dichroanone and (+)-Taiwaniaquinone H","A catalytic, enantioselective formal synthesis of (+)-dichroanone and (+)-taiwaniaquinone H is reported. The all-carbon quaternary stereocenter was constructed by asymmetric conjugate addition catalyzed by a palladium(II) (S)-tert-butylpyridinooxazoline complex. The unexpected formation of a [3.2.1] bicyclic intermediate required the identification of a new route. Analysis of the Hammett constants for para-substituted arenes enabled the rational design of a highly enantioselective conjugate addition substrate that led to the completion of the formal synthesis.",10.1021/ol5031537,2014-12-09,0.5859657680609239
European Journal of Organic Chemistry,Stereoselective Synthesis of Sofosbuvir through Nucleoside Phosphorylation Controlled by Kinetic Resolution,"The preparation of Sofosbuvir, the potent key component of recent Hepatitis C (HCV) infection therapies, is reported. The process is based on the dynamic kinetic resolution of the stereochemically unstable isopropyl‐2‐{[chloro(phenoxy)phosphoryl]‐amino}propanoate ( 8 ). A high stereoselectivity was obtained when the right protective group for 3′‐OH was chosen. Ester and carbonate‐based protective groups gave lower stereoselectivities, but benzyl protection allowed the phosphorylation to occur with a 92:8 ratio in favour of the product with the right configuration at the P‐stereogenic centre. Starting from the γ‐lactone of 2‐deoxy‐2‐fluoro‐2‐methylpentonic acid, the synthesis was accomplished in eight steps in 40 % overall yield using commercially available reagents, and without any enzymatic or chemical resolution technique.",10.1002/ejoc.201800158,2018-03-06,0.5859637949561095
Tetrahedron,Asymmetric synthesis of α-amino acid derivatives via an electrophilic amination of chiral amide cuprates with Li t-butyl-N-tosyloxycarbamate,,10.1016/s0040-4039(97)00477-2,1997-04-01,0.5859637389752991
Journal of Organic Chemistry,Synthesis of Human Ultraviolet Filter Compounds:  <i>O</i>-β-<scp>d</scp>-Glucopyranosides of 3-Hydroxykynurenine and 2-Amino-3-hydroxy-γ-oxobenzenebutanoic Acid,"The role of endogenous tryptophan-derived UV filters in aging lenses and in human cataract is becoming increasingly important. The two major UV filters found in the lenses of primates, the O -β- d -glucopyranosides of 3-hydroxykynurenine and 2-amino-3-hydroxy-γ-oxobenzenebutanoic acid, 1 and 2, were synthesized from the common benzoyl acrylate precursor 2-amino-3-hydroxybenzoylacrylic acid 10 . Synthesis of compound 3, the α- N -acetyl derivative of 1, was achieved using coupling of 2-nitro-3-benzyloxyacetophenone 4 with the sodium salt of diethyl acetamidomalonate as a key step. This is the first reported synthesis of the lenticular glucopyranoside 2 and the N -acetyl compound 3 .",10.1021/jo982321n,1999-05-01,0.5859622907105466
Organic Letters,Thia-Wittig-like Reactions as a New Route for the Stereoselective Synthesis of (<i>Z</i>)-Fluoroalkenoates,"Stereoselective syntheses of ( Z )-fluoroalkenoates 3a − g have been developed in three steps from the readily available fluorosulfide 5 and aldehydes. This preparation, involving a Durst reaction, was highly stereoselective and led to fluoroalkenes in 50−60% overall yields, without purification of intermediates.",10.1021/ol990178u,1999-10-17,0.5859610069646808
Journal of Organic Chemistry,"Total Synthesis of Pancratistatin Relying on the [3,3]-Sigmatropic Rearrangement","A new total synthesis of the antitumor alkaloid, pancratistatin (1), has been accomplished from readily available starting materials. Claisen rearrangement of the racemic dihydropyranethylene 17 was employed to construct the A and C rings with the appropriate stereochemistry. In addition, the Ireland-Claisen rearrangement of the enantiomerically pure 9 followed by ring-closing metathesis provided the important intermediate 24, thus implying that our approach could yield the enantioselective synthesis of (+)-pancratistatin. With the appropriately functionalized cyclohexene 24, stereo- and regiocontrolled functional group interchanges, such as iodolactonization, dihydroxylations, and a cyclic sulfate elimination reaction, facilitated the production of the target natural product.",10.1021/jo035371n,2003-12-12,0.5859601463368667
Angewandte Chemie International Edition,A Lewis Acid Catalyzed Intramolecular [4+3] Cycloaddition Route to Polycyclic Systems That Contain a Seven‐Membered Ring,"Two simple steps, including a new intramolecular [4+3] cycloaddition, are required for the preparation of polycycles that contain a seven-membered ring from 2-methyleneaziridines (see scheme). The diene component is introduced by selective lithiation/alkylation at C3 of the aziridine ring. Lewis acid catalyzed cyclization leads to the products in good yields with stereocontrol.",10.1002/anie.200461084,2004-12-01,0.5859589949153103
Organic Letters,"Asymmetric Synthesis of (−)-Brevipolide H through Cyclopropanation of the α,β-Unsaturated Ketone","Brevipolides are 5,6-dihydro-γ-pyrone derivatives, first reported in 2004 as the inhibitors of the chemokine receptor CCR5 and exhibiting cytotoxicity against cancer cells. Starting from the C2 symmetric diene-diol 2, ent-brevipolide H was synthesized for the first time in 11 steps. The anti-addition of the sulfur ylide to the α,β-unsaturated enones was developed to give the key cyclopropane moiety. The synthetic (-)-brevipolide H showed an IC50 value of 7.7 μM against PC-3 cells.",10.1021/ol502507k,2014-10-02,0.5859545522935444
Tetrahedron,"Synthesis and structure determination of SCR7, a DNA ligase inhibitor",,10.1016/j.tetlet.2016.06.037,2016-06-14,0.5859518996428028
Synlett,"Decagram-Scale Synthesis of N-{2-[4-(β-d-Glucopyranosyloxy)-2-methylphenyl]-1,1-dimethyl-2-oxoethyl}-3-methylthiophene-2-carboxamide (GPTC), a Metabolite of the Fungicide Isofetamid","Abstract A decagram-scale synthesis of N-{2-[4-(β-d-glucopyranosyloxy)-2-methylphenyl]-1,1-dimethyl-2-oxoethyl}-3-methylthiophene-2-carboxamide (GPTC), a metabolite of the fungicide isofetamid, has been achieved in a highly straightforward manner from the known compound 1-(4-hydroxy-2-methylphenyl)-2-methylpropan-1-one in eight steps with a 20% overall yield to provide a standard certified reference material for residue analysis in food.",10.1055/a-2178-1442,2023-09-19,0.5859471838021416
Angewandte Chemie International Edition,Asymmetric Total Synthesis of (−)‐Nakadomarin A,"A key intermediate in the first asymmetric synthesis of the marine alkaloid (−)-nakadomarin A (1), isolated from the marine sponge Amphimedon sp., was the optically active hydroisoquinoline 2. Two separate ring-closing-metathesis reactions were crucial to the construction of the 15- and 8-membered rings.",10.1002/anie.200453673,2004-03-30,0.5859435930465087
Tetrahedron,Synthesis of ketenimine via (N-alkylimino)acylpalladium complex intermediate,,10.1016/s0040-4039(01)92815-1,1977-01-01,0.5859433954709636
Organic Letters,Copper-Mediated Domino Cyclization/Trifluoromethylation/Deprotection with TMSCF<sub>3</sub>: Synthesis of 4-(Trifluoromethyl)pyrazoles,"A copper-mediated synthesis of 4-(trifluoromethyl)pyrazoles is described. In one step from readily accessible α,β-alkynic tosylhydrazones, a remarkable domino sequence of cyclization, trifluoromethylation, and detosylation takes place to furnish the 4-CF 3 N -H pyrazole cores with good functional group compatibility. The reaction conditions are mild and convenient, at room temperature in air, using the commercially available trifluoromethyltrimethylsilane (TMSCF 3 ) as the CF 3 source. The method can be applied to the synthesis of a 4-CF 3 analogue of the anti-inflammatory drug celecoxib.",10.1021/acs.orglett.6b03822,2017-01-12,0.5859400962519534
Tetrahedron,"An efficient synthetic approach to 4′,5,5″-triaryl-2,2′:6′,2″-terpyridines",,10.1016/j.tetlet.2015.12.006,2015-12-12,0.5859391410976162
Journal of Organic Chemistry,A Cascade Synthesis of Indoles,"We report herein an expedient method for the regioselective synthesis of indoles from o -haloanilines and α-ketol-derived N -tosylhydrazones. This two-step, modular synthesis of N -H indoles can be carried out conveniently without purification of intermediates.",10.1021/acs.joc.4c01190,2024-07-04,0.5859379030088488
Organic Letters,Synthesis of a Highly Functionalized Core of Verrillin,"An efficient stereoselective synthesis of furanoverrillin (5), a highly functionalized core of verrillin (1), is reported. The synthetic strategy is based on constructing bicyclic lactone 17 prior to the 10-membered ring macrocyclization. The effect of the C4 methyl group on the furan reactivity is also discussed.",10.1021/ol400872h,2013-04-30,0.5859337748441266
Organic Letters,Synthesis of the C(1)−C(18) Segment of Lophotoxin and Pukalide. Control of 2-Alkenylfuran (<i>E</i>/<i>Z</i>)-Configuration,[reaction: see text] The convergent synthesis of the fully functionalized C(1)-C(18) segment 24 of the furanocembranes lophotoxin and pukalide was accomplished in 11 steps and 10% overall yield. The key step was a stereoselective conversion of alkynoate 21 to trimethylsilyl 2-alkenylfuran 22.,10.1021/ol025861m,2002-04-24,0.5859277469538184
Angewandte Chemie International Edition,Cover Picture: Palladium‐Catalyzed Coupling of Aldehyde‐Derived Hydrazones: Practical Synthesis of Triazolopyridines and Related Heterocycles (Angew. Chem. Int. Ed. 45/2010),"Pharmaceutically active compounds …︁ …︁ and their intermediates require selective, efficient, and robust syntheses that utilize green chemistry principles. In their Communication on page 8395 ff., O. R. Thiel, M. Achmatowicz, and co-workers describe a two-step procedure involving selective palladium-catalyzed carbon–nitrogen bond formation followed by a clean oxidative cyclization that affords access to a variety of bicyclic and tricyclic heteroaromatic scaffolds.",10.1002/anie.201004361,2010-07-26,0.5859256228463212
Journal of Organic Chemistry,"Intramolecular Gold-Catalyzed and NaH-Supported Cyclization Reactions of <i>N-</i>Propargyl Indole Derivatives with Pyrazole and Pyrrole Rings: Synthesis of Pyrazolodiazepinoindole, Pyrazolopyrazinoindole, and Pyrrolopyrazinoindole","Gold-catalyzed and NaH-supported intramolecular cyclization of N-propargyl indole derivatives with pyrazole and pyrrole units attached to indole is described. An efficient route to the synthesis of pyrazolodiazepinoindole, pyrazolopyrazinoindole, and pyrrolopyrazinoindole has been established. First, N-propargyl 2-(1H-pyrazol-5-yl)-1H-indole and 2-(1H-pyrrol-2-yl)-1H-indole were synthesized. Introduction of various substituents into the alkyne functionality was accomplished by Sonogashira cross-coupling reaction. Gold-catalyzed cyclization of pyrazoles having a terminal alkyne afforded the 6-exo-dig cyclization product. However, exclusive formation of 7-endo-dig cyclization products was observed with internal alkynes. On the other hand, cyclization with NaH only resulted in the formation of 6-exo-dig cyclization products regardless of the substitution of the alkyne functionality. Allenic intermediates were postulated for this outcome.",10.1021/acs.joc.5b02419,2015-12-03,0.5859241626399894
Journal of the American Chemical Society,Assembly of the Limonoid Architecture by a Divergent Approach: Total Synthesis of (±)-Andirolide N via (±)-8α-Hydroxycarapin,We report the first total synthesis of the limonoid andirolide N using a 12-step sequence from commercially available materials. The final step of this route demonstrates the chemical feasibility of our biosynthetic proposal that andirolide N arises from 8α-hydroxycarapin. The strategic use of a degraded limonoid as a platform for the synthesis of more structurally complex congeners may be a general approach to obtain limonoids with diverse functional properties.,10.1021/jacs.6b12268,2016-12-21,0.5859192139385982
Synlett,Efficient and Scalable Synthesis of Pyridine Sulfonamides,"Short-step and scalable transformations from 2,6-dibromopyridine to 6-bromopyridine-2-sulfonamide by means of halogen-metal exchange and subsequent reaction with sulfuryl chloride followed by amidation are established. Application of the method for the synthesis of various pyridine sulfonamides is also described.",10.1055/s-0030-1259953,2011-04-18,0.5859124305542894
Synlett,The First Synthesis of Coniochaetones A and (±)-B: Two Benzopyranone Derivatives,All articles of this category An efficient synthesis of coniochaetone A and of racemate coniochaetone B was achieved by a short five-step procedure from methyl-di- O -methyl- p -orsellinate. The key step is a cascade reaction of 2′-hydroxy-6′-methoxy-4′-methyl-2-(methylsulfinyl)-acetophenone with succindialdehyde in the presence of piperidine which allows the direct building of the tricyclic benzopyranone structure. heterocycle - chromone - coniochaetone A - coniochaetone B - antifungal activity,10.1055/s-1998-1628,1998-03-01,0.5859049264201006
European Journal of Organic Chemistry,An Iterative Method for the Synthesis of Symmetric Polyynes,"Abstract An iterative synthetic route for obtaining symmetric polyynes was developed, consisting of a series of iodination and Stille coupling reactions. The starting materials employed in this pathway are simple and can be prepared easily. Polyynes containing up to seven C≡C bonds were synthesized using this method. This route is particularly effective for accessing polyynes with an odd number of C≡C bonds and has allowed for the synthesis of a new iodine‐capped polyyne, diiododecapentayne.",10.1002/ejoc.201200442,2012-07-10,0.5859035437496121
Synthesis,Enantioselective Synthesis of (–)-Stemoamide,An enantioselective synthesis of (–)-stemoamide is presented. Noyori’s ruthenium complex catalyzed asymmetric transfer hydrogenation of an alkynone delivered the ( S )-C8 stereogenic center in 97.7% ee. An iron(III) chloride promoted and bioinspired N -iminium ion cyclization afforded a 3:1 ratio of two diastereomers in favor of the cis -isomer. The diastereomeric ratio was enriched to 50:1 by a silver-catalyzed cycloisomerization. The subsequent dynamic ruthenium-catalyzed CO-insertion reaction secured an enantioselective total synthesis of (–)-stemoamide in 18% overall yield with high optical purity.,10.1055/s-0032-1317499,2012-10-25,0.5858998277079881
Synthesis,Stereoselective Synthesis of Fluorinated and Nonfluorinated Triazolo Analogues of Ceramides,"A series of diastereomeric fluorinated and nonfluorinated triazolo analogues of naturally occurring sphingolipids like dihydroceramide suitable for physicochemical and medicinal chemistry applications were prepared enantioselectively. Key steps of the synthetic sequence are asymmetric Sharpless dihydroxylation of α,β-unsaturated esters to diols, regioselective ring opening of derived cyclic sulfates by azide, 1,3-dipolar cycloaddition with alkynes, and reduction of the ester groups.",10.1055/s-0029-1218591,2009-12-07,0.5858848670507012
Journal of the American Chemical Society,Enantioselective Synthesis of Planar Chiral Ferrocenes via Pd(0)-Catalyzed Intramolecular Direct C–H Bond Arylation,"A highly efficient synthesis of planar chiral ferrocenes by enantioselective Pd(0)-catalyzed direct C-H arylation from readily available starting materials under mild reaction conditions was developed (up to 99% yield, 99% ee). The products can be easily transformed to the highly efficient planar ferrocene ligands, which have demonstrated high efficiency in Pd-catalyzed asymmetric allylic alkylation and amination reactions.",10.1021/ja500444v,2014-03-13,0.5858826467760863
Organic Letters,Highly Enantioselective Synthesis of (2<i>S</i>)-α-(Hydroxymethyl)-glutamic Acid by the Catalytic Michael Addition of 2-Naphthalen-1-yl-2-oxazoline-4-carboxylic Acid <i>tert</i><i>-</i>Butyl Ester,"[reaction: see text]. Highly enantioselective synthesis of a potent metabotropic receptor ligand, (2S)-alpha-(hydroxymethyl)-glutamic acid (2, HMG) was accomplished by the catalytic Michael addition of 2-naphthalen-1-yl-2-oxazoline-4-carboxylic acid tert-butyl ester (3b), using the phosphazene base, BEMP, in CH(2)Cl(2) at -60 degrees C in the presence of (S)-binaphthyl quaternary ammonium salt 4.",10.1021/ol050920s,2005-06-30,0.5858739981910556
Journal of Organic Chemistry,Conversion of Marcfortine A to Paraherquamides <i>via</i> a Novel Platinum−Oxygen-Mediated Ring Contracting Reaction,"The paraherquamides and marcfortines represent a novel class of anthelmintics. The sole structural difference between marcfortine A ( 1 ) and paraherquamide A ( 5 ) occurs in ring G. By employing a ring contracting reaction utilizing platinum and oxygen (Pt/O 2 ) at a key point in the synthesis, we were able to directly convert marcfortine A to the intermediate 16-oxoparherquamide B ( 2 ), thereby eliminating six steps in our earlier synthesis. Paraherquamide A was also prepared from 14α-hydroxymarcfortine A ( 3 ) and 14α-hydroxy-14β-methylmarcfortine A ( 6 ) using Pt/O 2 chemistry. Additionally, parahequamide derivative 20 was synthesized from marcfortine A derivative 16 .",10.1021/jo971227o,1997-10-01,0.5858683976722396
Journal of Organic Chemistry,Copper-Mediated Domino Cyclization/Trifluoromethylation of Propargylic <i>N</i>-Hydroxylamines: Synthesis of 4-Trifluoromethyl-4-isoxazolines,"A Cu(OTf) 2 -mediated synthesis of trifluoromethylated 4-isoxazolines is described. In one step from readily available propargylic N -hydroxylamines, a domino 5- endo - dig cyclization, followed by trifluoromethylation, takes place to construct the 4-isoxazoline core with concomitant installation of the CF 3 group at the C-4 position. Such compounds could also be useful precursors for the preparation of α-trifluoromethyl β-amino ketones.",10.1021/acs.joc.7b03191,2018-02-06,0.5858650736023416
Synthesis,The Synthesis of Novel 4-(Aminomethyl)oxazoline Ligands,"A practical route to 2,3-bis(amino)-1-alcohols has been developed and utilized in the synthesis of a number of novel bis(oxazoline) ligands.",10.1055/s-2005-918477,2005-01-01,0.5858459663629585
Angewandte Chemie International Edition,"Synthesis of Atropisomerically Defined, Highly Substituted Biaryl Scaffolds through Catalytic Enantioselective Bromination and Regioselective Cross‐Coupling","A selective sequence: An enantioselective synthesis (see scheme) of atropisomerically defined p-terphenyls, as well as tetra- and pentaaryl compounds is reported. The synthesis proceeds through sequential atropisomer-selective electrophilic aromatic substitution and regioselective palladium-catalyzed cross-coupling reactions.",10.1002/anie.201101147,2011-04-21,0.5858457459774555
Organic Letters,Synthesis of α-Fluorinated Phosphonates from α-Fluorovinylphosphonates:  A New Route to Analogues of Lysophosphatidic Acid,"A versatile, efficient method for the preparation of alpha-monofluoromethylene (-CHF-) phosphonates from alpha-fluorovinylphosphonate provides access to a class of lysophosphatidic acid (LPA) receptor-subtype agonists. In addition, sn-2 O-methylation of alpha-monofluoromethylene phosphonates using trimethylsilyldiazomethane generated sn-1-acyl, 2-O-methyl alpha-monofluoromethylene derivatives. Finally, a novel method for the selective etherification of 1,2-diols was developed and a new class of sn-1 O-methyl, 2-acyl alpha-monofluoromethylene LPA analogues was prepared. [reaction: see text]",10.1021/ol034597+,2003-05-31,0.5858445208646162
European Journal of Organic Chemistry,Asymmetric Synthesis of Atorvastatin Calcium through Intramolecular Oxidative Oxygen‐Nucleophilic Bromocyclization,"The stereocontrolled synthesis of atorvastatin calcium starting from commercially available d‐ aspartic acid using an intramolecular oxidative oxygen‐nucleophilic bromocyclization of a homoallylic tert ‐butyl carbonate is described. This strategy allows the formation of the chiral syn ‐1,3‐diol moiety with the desired stereochemistry, and provides a functionalized bromomethyl group for the construction of the atorvastatin side‐chain with high regio‐ and diastereoselectivity. This route is attractive as it represents an efficient and environmentally sensitive approach to the large‐scale synthesis of statins and their analogues.",10.1002/ejoc.201700387,2017-05-15,0.5858373440729318
Journal of Organic Chemistry,Divergent and Selective Synthesis of Functionalized Fluoroalkenes through Switchable Photocatalytic Dialkylation/Cyclization of Alkenes,"A switchable photocatalytic dialkylation/cyclization of alkenes with α-CF 3 alkenes and protic C(sp 3 )–H feedstocks was readily achieved by simply switching the commercially available base and/or its stoichiometry. This mild strategy enabled the divergent one-pot synthesis of diverse functionalized fluoroalkenes including gem-difluoroalkenes, monofluorocyclohexenes, and 2-fluoropyrrolines in a single operational step.",10.1021/acs.joc.5c01215,2025-07-24,0.5858287610790285
Tetrahedron,Synthesis of a new generation reverse transcriptase inhibitor via the BCl3/GaCl3-induced condensation of anilines with nitriles (sugasawa reaction),,10.1016/0040-4039(94)85011-9,1994-09-01,0.5858285088924883
Organic Letters,"Formal Total Synthesis of Actinoranone and Asymmetric Synthesis of Labda-7,13-(<i>E</i>)-dien-15-ol","The syntheses of the polyketide and terpenoid fragments of actinoranone are reported in a concise fashion, relying on catalytic methods. Minimization on the use of protecting groups and redox reactions allowed the synthesis of the carbon backbone of actinoranone in 20 steps (11 steps for LLS). The asymmetric synthesis of labda-7,13-(E)-dien-15-ol is also disclosed.",10.1021/acs.orglett.7b01287,2017-05-31,0.5858274772430632
Journal of Organic Chemistry,Asymmetric Synthesis of Taiwaniaquinone H via a Late-Stage Oxidative Decarboxylation,"The asymmetric syntheses of naturally occurring biologically relevant abeo -abietane diterpenoids, (−)-taiwaniaquinone G ( 1a ), and H ( 1b ) have been reported via a chiral pool strategy starting from commercially available abietic acid. A ring contraction of the middle ring of the [6,6,6]-carbotricyclic abietane diterpenoid core was carried out under the Wolff rearrangement. Finally, the synthesis of (−)-taiwaniaquinone H ( 1b ) was completed via a one-pot CAN-mediated oxidative decarboxylation.",10.1021/acs.joc.4c02448,2024-11-22,0.5858263149988876
Journal of the American Chemical Society,Total Synthesis of the Ramoplanin A2 and Ramoplanose Aglycon,"Full details of a convergent total synthesis of the ramoplanin A2 and ramoplanose aglycon are disclosed. Three key subunits composed of residues 3−9 (heptapeptide 15 ), pentadepsipeptide 26 (residues 1, 2 and 15−17), and pentapeptide 34 (residues 10−14) were prepared, sequentially coupled, and cyclized to provide the 49-membered depsipeptide core of the aglycon. Key to the preparation of the pentadepsipeptide 26 incorporating the backbone ester was the asymmetric synthesis of an orthogonally protected l -threo- β -hydroxyasparagine and the development of effective and near-racemization free conditions for esterification of its hindered alcohol (EDCI, DMAP, 0 °C). The coupling sites were chosen to maximize the convergency of the synthesis including that of the three subunits, to prevent late stage racemization of carboxylate-activated phenylglycine-derived residues, and to enlist β -sheet preorganization of an acyclic macrocyclization substrate for 49-membered ring closure. By altering the order of final couplings, two macrocyclization sites, Phe 9 − d -Orn 10 and Gly 14 −Leu 15, were examined. Macrocyclization at the highly successful Phe 9 − d -Orn 10 site (89%) may benefit from both β -sheet preorganization as well as closure at a d -amine terminus within the confines of a β -turn at the end of the H-bonded antiparallel β -strands. A more modest, but acceptable macrocyclization reaction at the Gly 14 −Leu 15 site (40−50%) found at the other end of the H-bonded antiparallel β -strands within a small flexible loop may also benefit from preorganization of the cyclization substrate, is conducted on a substrate incapable of competitive racemization, and accommodates the convergent preparation of analogues bearing depsipeptide modifications. Deliberate late-stage incorporation of the subunit bearing the labile depsipeptide ester and a final stage Asn 1 side-chain introduction provides future access to analogues of the aglycons which themselves are equally potent or more potent than the natural products in antimicrobial assays.",10.1021/ja0212314,2003-01-23,0.585824689407517
Tetrahedron,Total synthesis of (+) monomorine I from chiral cyclic β-enamino ester,,10.1016/s0040-4039(00)92707-2,1991-07-01,0.585820758363167
Journal of Organic Chemistry,"Novel Route to 2,3-Substituted Benzo[<i>b</i>]thiophenes via Intramolecular Radical Cyclization","A novel route to 2,3-substituted benzo[b]thiophenes by intramolecular radical cyclization of polarized ketene dithioacetals derived from o-bromoarylacetonitriles or the corresponding 3-(methylthio)-3-alkyl/aryl/heteroaryl analogues has been reported.",10.1021/jo900615p,2009-07-02,0.5858152462616876
Journal of the American Chemical Society,Concise Enantioselective Total Synthesis of Cardiotonic Steroids 19-Hydroxysarmentogenin and Trewianin Aglycone,"The expedient and scalable approach to cardiotonic steroids carrying oxygenation at the C11- and C19-positions has been developed and applied to the total asymmetric synthesis of steroids 19-hydroxysarmentogenin and trewianin aglycone as well as to the assembly of the panogenin core. This new approach features enantioselective organocatalytic oxidation of an aldehyde, diastereoselective Cu(OTf)2-catalyzed Michael reaction/tandem aldol cyclizations, and one-pot reduction/transposition reactions allowing a rapid (7 linear steps) assembly of a functionalized cardenolide skeleton. The ability to quickly set this steroidal core with preinstalled functional handles and diversity elements eliminates the need for difficult downstream functionalizations and substantially improves the accessibility to the entire class of cardenolides and their derivatives for biological evaluation.",10.1021/jacs.6b04029,2016-05-27,0.585807044090951
Synlett,"Practical Protocols for the Preparation of Highly Enantioenriched Silyl Ethers of (R)-3-Hydroxypentan-2-one, Building Blocks for the Synthesis of Macrolide Antibiotics","Methacrolein is transformed in three steps to ( R )-3- tert -butyldiphenylsilyloxypentan-2-one or ( R )-3- tert -butyldimethylsilyloxypentan-2-one, compounds which serve as building blocks for the construction of macrolide antibiotics. The route is practical, highly enantioselective, and easily scaled.",10.1055/s-0035-1560972,2015-11-24,0.5858033128632011
Synthesis,"An Efficient Synthesis of 1-Methyl-4,5,6,7-tetrahydro-1H-pyrrolo[2,3-c]pyridine and Its N6-Substituted Analogues","An efficient synthesis of 1-methyl-4,5,6,7-tetrahydro-1 H -pyrrolo[2,3- c ]pyridine hydrochloride was achieved using simple sodium borohydride reduction of 6-benzyl-1-methyl-1 H -pyrrolo[2,3- c ]pyridin-6-ium bromide as the key step followed by its debenzylation with hydrogen over palladium on carbon on a multigram scale. Similarly, a series of N 6 -substituted 1-methyl-1 H -pyrrolo[2,3- c ]pyridin-6-ium halides were synthesized and reduced with sodium borohydride, showing this method to be applicable for the synthesis of different N 6 -substituted 1-methyl-4,5,6,7-tetrahydro-1 H -pyrrolo[2,3- c ]pyridines.",10.1055/s-0032-1318346,2013-02-27,0.5858011584701144
Organic Letters,Intramolecular [2 + 2] Cycloadditions of Alkyl(phenylthio)ketenes: Total Synthesis of (+)-Sphaerodiol,Asymmetric total synthesis of (+)-sphaerodiol (2) has been achieved. A key step is an intramolecular [2 + 2] cycloaddition of alkyl(phenylthio)ketene for rapid assembly of the decalin ring.,10.1021/acs.orglett.8b00407,2018-03-13,0.5857982277169956
Journal of Organic Chemistry,Total Synthesis of Proposed Auranthine,"Starting from CBz-protected glutamic anhydride and Boc-protected o-aminobenzyl amine, the first total synthesis of proposed structure of auranthine has been reported. An intramolecular aza-Wittig reaction involving a lactam carbonyl group that delivered the diazepine core unit was the key step in the synthesis.",10.1021/jo100400z,2010-03-22,0.5857968064323863
Organic Letters,Aryne Relay Chemistry en Route to Aminoarenes: Synthesis of 3-Aminoaryne Precursors via Regioselective Silylamination of 3-(Triflyloxy)arynes,"A facile synthetic method for preparing 3-amino-2-silylaryl triflates via regioselective silylamination of 3-(triflyloxy)arynes with N-silylamines is described. Fluoride-mediated generation of 3-aminobenzyne from 3-amino-2-silylphenyl triflate, easily prepared by this method, in the presence of various arynophiles efficiently afforded diverse aniline derivatives, including a 5-aminocoumarin derivative, demonstrating the utility of aryne relay approach.",10.1021/acs.orglett.6b03304,2016-11-22,0.5857797602381929
Journal of Organic Chemistry,Design of a Nonreductive Method for Chemoselective Cleavage of Hydrazines in the Presence of Unsaturations:  Application to a Stereoconvergent Three-Component Synthesis of (−)-Methyl Palustramate,"A chemoselective hydrazine (N-N) cleavage methodology that preserves the integrity of alkenes was developed based on a mild acid-promoted fragmentation of tetrasubstituted 1-(trimethylsilylmethyl)-1-benzylhydrazines. This strategy was applied to a concise asymmetric synthesis of (-)-methyl palustramate (4), which featured a convergent stereo- and regioselective sequential three-component aza[4+2]cycloaddition/allylboration/retro-sulfinyl-ene rearrangement between diene 1f, dienophile 2b, and propionaldehyde to afford cis-2-carboxy-6-hydroxyalkylpiperidine 25. The acid-promoted hydrazinolysis of 25 cleanly afforded key intermediate 31, and the latter led to target 4 in four steps after a series of functional group transformations.",10.1021/jo048581o,2004-11-01,0.5857796861168435
Organic Letters,"Synthesis of the 10-Azatricyclo[3.3.2.0<sup>4,8</sup>]decane Core of C<sub>20</sub>-Diterpenoid Alkaloid Racemulsonine via Iodine(III) Promoted Transannular Aziridination Reaction",The functionalized A/E/F ring system of C20-diterpenoid alkaloid racemulsonine has been efficiently synthesized. The Key steps involved a diastereoselective Au(I)-catalyzed annulation to form cis-fused cyclopentene and a PIDA promoted transannular aziridination of primary amine followed by regio- and stereoselective ring cleavage of bridged aziridine.,10.1021/ol400755x,2013-04-15,0.5857793558405582
Journal of Organic Chemistry,Total Synthesis of (−)-α-Kainic acid via Chirality Transfer through Ireland–Claisen Rearrangement,The total synthesis of (-)-α-Kainic acid is accomplished using a linear strategy involving Noyori asymmetric reduction and chirality transfer through Ireland-Claisen rearrangement as key steps.,10.1021/jo400001t,2013-03-07,0.5857762392781998
Tetrahedron,First efficient preparation of enantiopure 10-bromofenchone: the key intermediate to C10-substituted fenchone-derived chiral sources,,10.1016/s0040-4039(01)01316-8,2001-09-01,0.585768911051793
Organic Letters,Shortest Enantioselective Total Syntheses of (+)-Isolaurepinnacin and (+)-Neoisoprelaurefucin,"High Resolution Image Download MS PowerPoint Slide The shortest enantioselective total syntheses of (+)-isolaurepinnacin and (+)-neoisoprelaurefucin have been accomplished. These syntheses were based on a common parallel synthetic strategy using Prins–Peterson cyclization in their core construction. In only one step, a seven-membered ring oxacycle with the correct cis -stereochemistry ring closure and the Δ 4 position of the endocyclic double bond in (+)-isolaurepinnacin was obtained. This unsaturation was also necessary to accede to the bromodioxabicycle on (+)-neoisoprelaurefucin.",10.1021/acs.orglett.2c01769,2022-07-14,0.5857673720121163
European Journal of Organic Chemistry,"Flexible Approach to (5<i>Z</i>,9<i>Z</i>)‐Dienoic Fatty Acids Relevant to the Synthesis of Demospongic Acids and Related Natural Products","A flexible and efficient synthesis of the potent human topoisomerase inhibitor (5 Z ,9 Z )‐eicosa‐5,9‐dienoic acid was explored; the presented method represents a generally applicable approach towards demospongic acids and related natural products. Key steps of the synthesis involve chemoselective hydroboration, Corey–Fuchs alkynylation, Z ‐selective Lindlar reduction, tetrapropylammonium perruthenate catalyzed direct oxidation of a primary alcohol to the corresponding acid, and Arndt–Eistert homologation. Thus, the total synthesis of (5 Z ,9 Z )‐eicosa‐5,9‐dienoic acid was achieved in 10 steps in an overall yield of 20 %.",10.1002/ejoc.201600746,2016-08-03,0.5857645351356332
Organic Letters,Enantioselective Synthesis of Sphingadienines and Aromatic Ceramide Analogs,"A new approach to the synthesis of sphingoid bases has been developed. The strategy is based on Sonogashira coupling of a chiral acetylenic carbamate that can be prepared in enantiomerically enriched form from 2,3-epoxy-4-pentyn-1-ol, which is readily accessible by Sharpless asymmetric epoxidation. Several N-Boc-sphingadienines and aromatic ceramide analogs have been synthesized.",10.1021/ol202064j,2011-09-02,0.5857599126499609
Tetrahedron,First practical asymmetric synthesis of R-(−)-and s-(+)-mevalonolactones from a single achiral precursor,,10.1016/s0040-4039(01)91304-8,1984-01-01,0.5857597983934185
Tetrahedron,A divergent approach to the total synthesis of the marine pyridoacridine alkaloid eilatin and its synthetic isomer isoeilatin,,10.1016/j.tetlet.2015.01.176,2015-02-03,0.5857560292788476
Tetrahedron,"An efficient synthesis for eslicarbazepine acetate, oxcarbazepine, and carbamazepine",,10.1016/j.tetlet.2013.03.089,2013-03-27,0.5857530613168062
Synlett,Enantioselective Syntheses of (-)-Kinamycin F and (-)-Lomaiviticin Aglycon,"Synthetic studies of the diazofluorene antitumor antibiotics, the kinamycins and lomaiviticins, are described.",10.1055/s-0030-1261147,2011-08-31,0.5857530599955894
Tetrahedron,A new and unequivocal synthesis of isoxanthopterin-6-carboxylic acid (cyprino-pourpre B),,10.1016/s0040-4039(01)86816-7,1973-01-01,0.5857528831162908
Journal of the American Chemical Society,Total Synthesis of (−)-FR901483,"The first synthesis of the immunosuppressant (−)-FR901483 ( 1 ) has been accomplished in 2% overall yield from O -methyltyrosine methyl ester ( 31 ) in 22 steps establishing the absolute stereochemistry of the natural product. A 1,3-dipolar cycloaddition of nitrone 5b with ethyl acrylate gave predominantly isoxazolidine 4b that was hydrogenated to give azaspirolactam 3b with the correct absolute and relative stereochemistry for the synthesis of 1 . Elaboration of 3b to keto aldehyde 38 and an intramolecular aldol reaction gave tricyclic keto alcohol 40 with reasonable selectivity using KO- t -Bu in t -BuOH. Further elaboration afforded (−)- 1 in 9 steps with spectral data identical to that of the natural product.",10.1021/ja991160h,1999-08-12,0.5857527398637973
Synthesis,A Practical Synthesis of Cycloalkylphosphonates from Trichloromethylphosphonates,"All articles of this category Cycloalkylphosphonates 5 with ring size varying from 4 to 6 were synthesized in good overall yields, in two steps from trichloromethylphosphonates and ω -dibromoalkanes, via the corresponding α -trimethylsilyl cycloalkylphosphonates 4 . Cycloalkylphosphonates 5 are prepared in two steps from trichloromethylphosphonates 1 , via α -silylated cycloalkylphosphonates 4 .",10.1055/s-1995-4427,1995-03-01,0.5857517135346398
Synthesis,A Simple and Efficient Synthesis of N-Substituted Cyclohex-3-enamines,"A straightforward preparation of N-substituted cyclohex-3-enamines starting from the commercially available trans-4-aminocyclohexanol hydrochloride is described. Cyclohex-3-enamino-functionalized compounds have proven to be interesting intermediates in medicinal chemistry. The method here described is cheaper, more scalable and tolerant of a broader variety of functional groups than those found in the literature for this type of compound.",10.1055/s-0029-1216989,2009-09-03,0.5857511755875932
European Journal of Organic Chemistry,Cationic Polyene Cyclization for Taiwaniaquinoid Construction,"An acid‐catalyzed polyene cyclization has been used to rapidly generate the 6/5/6‐fused ring system of the taiwaniaquinoid natural products. The cis ‐fused diastereomer was formed selectively, which enabled a step‐efficient synthesis of (±)‐5‐ epi ‐taiwaniaquinone G.",10.1002/ejoc.201601349,2016-11-29,0.5857488302274936
Angewandte Chemie International Edition,A New Synthesis Route to Enantiomerically Pure Jasmonoids,An important class of phytohormones are jasmonoids. A variety of jasmonoids in the natural cis configuration are now accessible by a general strategy. Key building blocks are enantiomerically pure lactones of type A with a leaving group Y which can be prepared by a catalytic asymmetric synthesis. Reaction with zinc cyanocuprates affords products with the requisite cis configuration that can be transformed into the target compounds in a few steps.,10.1002/1521-3773(20021104)41:21<4054::aid-anie4054>3.0.co;2-k,2002-10-31,0.5857469683121
Journal of Organic Chemistry,"Access to the Surugatoxin Alkaloids: Chemo-, Regio-, and Stereoselective Oxindole Annulation",We report the synthesis of an aglycone of the surugatoxin family. The synthesis of this surugatoxin core was accomplished in 13 steps using a new oxindole annulation and late-stage enamine oxidation.,10.1021/acs.joc.5b02053,2015-11-05,0.5857452931877426
Tetrahedron,Highly stereoselective synthesis of enantiomerically pure β-hydroxy-γ-sulfenyl-γ-butyrolactone by asymmetric Pummerer type cyclization,,10.1016/s0040-4039(00)00562-1,2000-05-01,0.5857433015410791
Angewandte Chemie International Edition,"Total Synthesis of Naturally Configured Pyrrhoxanthin, a Carotenoid Butenolide from Plankton","A carotenoid from the chemical kitchen: Two sequential Stille couplings of an unsymmetric distannane building block with a bromoolefin and a bromoalkyne terminated a highly convergent synthesis of the title compound, pyrrhoxanthin (see scheme).",10.1002/anie.200801638,2008-09-02,0.5857413670042825
Organic Letters,Total Synthesis of Pargamicin A,"We report the total synthesis and configurational assignment of pargamicin A, a highly oxidized nonribosomal peptide that potently inhibits the growth of drug-resistant bacteria. Our synthetic approach relies on late-stage piperazine ring formation and careful selection of condensation reagents to assemble the densely substituted hexapeptide backbone. This work enables the synthesis of pargamicin congeners for the development of structure-activity relationships and informs strategies for accessing other sterically congested piperazic acid-containing natural products.",10.1021/acs.orglett.2c03861,2022-12-14,0.5857393927921309
Synlett,A Versatile Chiral Pyrrolidine Aldehyde Building-Block for Synthesis and Formal Synthesis of ent-Nakadomarin A,"A stable, simple to synthesise and versatile chiral aldehyde building-block has been developed, its reactivity in Wittig, Horner-Wadsworth-Emmons and Grignard reactions investigated, and its use is demonstrated in a highly efficient synthesis of an intermediate in Dixon’s synthesis of nakadomarin A.",10.1055/s-0029-1219182,2010-01-11,0.5857378088245869
Tetrahedron,A new synthesis of the corticosteroid side chain,,10.1016/s0040-4039(00)98812-9,1990-01-01,0.5857215329657735
Tetrahedron,Glycosyl transfer by isopropenyl glycosides: Trisaccharide synthesis in one pot by selective coupling of isopropenyl and n-pentenyl glycopyranosides,,10.1016/0040-4039(94)88449-8,1994-12-01,0.5857119202860019
Organic Letters,Total Synthesis of Spiruchostatin A via Chemoselective Macrocyclization using an Accessible Enantiomerically Pure Latent Thioester,"HDAC inhibitor Spiruchostatin A was synthesized via a route that differs significantly from previously reported routes. The key step involves a latent thioester that initiates a chemoselective transformation similar to native chemical ligation to form the macrocyclic alanine-cysteine amide bond. The easily prepared latent thioester--the first such moiety reported in enantiomerically pure form--is designed with a pendant carboxylic acid to serve as a solid-phase linker for the synthesis of cyclic, cysteine-containing, peptidic materials.",10.1021/ol900436f,2009-03-30,0.5857070429418735
Journal of Organic Chemistry,Synthesis of Two Fluoro Analogues of the Nicotinic Acetylcholine Receptor Agonist UB-165,"Two racemic fluoropyridine analogues 4 and 5 of the potent nicotinic agonist UB-165 have been synthesized. Halogenated pyridines 7 and 12 provided the organometallic reagents needed for the Negishi and Suzuki coupling reactions used for the preparation of 4 and 5, and the N-vinyloxycarbonyl protecting group of 8 and 15 was cleaved using a novel trifluoroacetic acid-mediated deprotection protocol. Analogue 4 retained high binding affinity at rat brain alpha4beta2 and alpha7 nicotinic receptors.",10.1021/jo026698b,2003-02-20,0.5856987929485005
Organic Letters,Catalytic Dearomatization Approach to Quinolizidine Alkaloids: Five Step Total Synthesis of (±)-Lasubine II,"A series of high-yielding silver(I)-catalyzed cyclization reactions of pyridine-, isoquinoline-, and pyrazine-ynones are described. The operationally simple and mild reaction conditions are a significant improvement over previously reported thermal cyclizations. The quinolizinone products were also used in a novel dearomatization strategy to prepare 0.53 g of the alkaloid lasubine II in five steps and 36% overall yield.",10.1021/acs.orglett.6b03017,2016-11-30,0.5856978145345304
Tetrahedron,"Inter vs intramolecular amidoalkylations of aromatics - a new synthesis of oxindoles, isoquinolones and benzazepinones",,10.1016/s0040-4039(01)85559-3,1980-01-01,0.585683090054544
Synthesis,"Synthesis of (-)-(5<i>R</i>,6<i>S</i>)-6-Acetoxyhexadecanolide, a Mosquito Oviposition Attractant Pheromone of <i>Culex pipiens fatigans</i>","Asymmetric total synthesis of (-)-(5R,6S)-6-acetoxyhexadecanolide has been achieved via a key intermediate which was prepared by a Grignard reaction from an alcohol. The alcohol was easily accessed via two different routes.",10.1055/s-2006-950341,2006-11-02,0.5856828588599463
Journal of Organic Chemistry,A Practical Synthesis of Differentially Protected 2-(Hydroxymethyl)piperazines,"An efficient and scalable synthesis of three differentially protected 2-(hydroxymethyl)piperazines is presented, starting from optically active and commercially available (2S)-piperazine-2-carboxylic acid dihydrochloride. These synthetic building blocks are useful in the preparation of biologically active compounds and as chemical scaffolds for the construction of combinatorial libraries.",10.1021/jo701465h,2007-10-01,0.5856797371549449
Journal of Organic Chemistry,"Preparation and Synthetic Applications of (<i>S</i>)- and (<i>R</i>)-<i>N</i>-Boc-<i>N,O</i>-isopropylidene-α-methylserinals:  Asymmetric Synthesis of (<i>S</i>)- and (<i>R</i>)-2-Amino-2-methylbutanoic Acids (Iva)",This report describes an efficient and convenient large-scale synthesis procedure for (S)- and (R)-N-Boc-alpha-methylserinal acetonides (3 and 4) starting from (R)-2-methylglycidol 5. The application of both of these compounds as valuable chiral building blocks in the asymmetric synthesis of alpha-methylamino acids is also demonstrated by the synthesis of (S)- and (R)-isovalines (Iva) (6 and 7).,10.1021/jo990957o,1999-10-01,0.5856769279629456
Tetrahedron,The enantio- and diastereoselective synthesis of the first phospho-statine derivative,,10.1016/s0040-4039(00)84523-2,1986-01-01,0.585675705286983
European Journal of Organic Chemistry,Synthesis and Supramolecular Properties of a Novel Octaphosphonate Porphyrin,"Abstract Two complementary routes were developed for preparing novel octaphosphonate porphyrins. The use of protected/deprotected phosphonate‐substituted precursors in the rational synthesis gave an overall yield 16 %. A more streamlined synthetic path gave 21 % overall yield of the target molecule. Octaphosphonate porphyrin possesses promising properties in supramolecular aggregate formation with cyclam. Cofacial reversible self‐assembly of a meso ‐substituted octaphosphonate porphyrin with cyclam yields micrometer‐long nanowires with a height of about 1–1.5 nm. The resulting wires were characterized by UV/Vis absorption, emission and atomic force microscopy and transmission electron microscopy.(© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2009)",10.1002/ejoc.200900589,2009-07-14,0.5856668489341441
Tetrahedron,Enantioselective synthesis of β-amino-diacids,,10.1016/j.tetlet.2005.09.114,2005-10-11,0.5856656006406932
Tetrahedron,"Organocatalyzed enantioselective synthesis of 6-amino-5-cyanodihydropyrano[2,3-c]pyrazoles",,10.1016/j.tetlet.2009.02.210,2009-03-05,0.5856656006406932
Synlett,A Highly Diastereoselective Epoxidation of N-Boc 2-Alkenyloxazolidines: Application in Asymmetric Synthesis,"All articles of this category N -Boc 2-alkenyloxazolidines derived from ( R )-phenylglycinol underwent a highly diastereoselective bromocarbamoylation when treated with NBS. Reaction of the resulting bicyclic urethanes with sodium ethoxide yielded diastereomerically pure oxazolidine epoxides. This new methodology was applied to the enantioselective synthesis of the anti isomer of the taxol side chain methyl ester, i.e. (2 R ,3 R )- N -benzoyl-3-phenylisoserine methyl ester. oxazolidine - bromocarbamoylation - asymmetric epoxidation - taxol side chain",10.1055/s-1995-5159,1995-10-01,0.5856629665810013
Organic Letters,"A Simple and Stereospecfic Route to 2,6-Disubstituted 4-Hydroxypiperidines. Synthesis of Dendrobate Alkaloid (+)-241D and Formal Synthesis of (−)-Indolizidine 167B","The condensation of enantiopure beta-amino esters with beta-ketoesters followed by cyclization and decarboxylation afforded 2,3-dihydro-4-pyridones 3, which were selectively hydrogenated to provide 2,6-disubstituted 4-hydroxypiperdines.",10.1021/ol006176n,2000-07-18,0.5856556979542044
Synlett,Simple and Diastereoselective Synthesis of an A-Ring Precursor of Dihydroxyvitamin D<sub>3</sub> (Calcitriol) by Photooxygenation,"A convenient synthesis of a racemic A-ring precursor of dihydroxyvitamin D3 (calcitriol) is described. The key step involves the singlet oxygen ene reaction of the Lythgoe lactone, which proceeds with excellent regio- and good diastereoselectivities. Strong polar interactions are operative during the attack of 1O2 to the double bond, which is important for the mechanism of such reactions.",10.1055/s-2004-835647,2004-11-08,0.58565017632873
Synthesis,Synthesis of Orthogonally Protected (±)-3-Amino-4-anilidopiperidines and (±)-3-N-Carbomethoxyfentanyl,"The synthesis of orthogonally protected cis- and trans-3-amino-4-anilidopiperidine derivatives has been accomplished in six steps, starting from readily accessible 4-piperidone derivatives. The last three steps, i.e., N-acylation, Hofmann rearrangement, and carbamate cleavage, involved separated (±)-cis and (±)-trans intermediates. Complete retention of configuration was observed at position 3 of the piperidine ring. Specifically protected positions 1 and 3 at the piperidine scaffold allow for selective deprotection and introduction of diverse substituents at the respective nitrogen sites. The orthogonally protected anilidopiperidines open avenues to potentially pharmacologically active compounds, including opioids and various bivalent ligands for G protein-coupled receptors. In addition, a prototype of a novel class of fentanyl derivatives, possessing a 3-amino group, was synthesized by using the same approach.",10.1055/s-0036-1588985,2017-04-03,0.5856445285844726
Organic Letters,"Total Synthesis of (+)-Sch 725680: Inhibitor of Mammalian A–, B–, and Y–Family DNA Polymerases","The total synthesis of (+)-Sch 725680, a member of the hydrogenated azaphilone family, has been accomplished. The synthesis confirmed the absolute configuration and biological activities of the natural product. A key reaction to construct a hydrogenated azaphilone core skeleton is a Ti-mediated aldol reaction.",10.1021/ol301865u,2012-08-28,0.5856423898718245
Organic Process Research & Development,An Improved Process for the <i>N</i>-Alkylation of Indoles Using Chiral <i>N</i>-Protected 2-Methylaziridines,An improved process for the N -alkylation of indoles using N -protected homochiral aziridines has been developed. This procedure allows reduced quantities of homochiral starting material to be used and leads to improved overall yields and operability.,10.1021/op020078v,2002-11-14,0.5856422963493214
Synlett,Synthesis of the Skipped Polyene Chain and Its Neighboring Highly Oxygenated Pyran Ring en route to Delivering the C(43)-C(67) Subsector of Amphidinol 3,An approach toward a total synthesis of amphidinol 3 that focuses on elaboration of the C(43)-C(67) subunit is described. The Julia-Kocienski reaction constitutes a straightforward way to unite the skipped polyolefin chain to the adjacent highly functionalized pyran ring.,10.1055/s-2005-918960,2005-10-27,0.5856410162831744
Synthesis,"A Convenient Preparation of Thieno[3,2-c]pyrazole","A practical synthesis of multigram quantities of 1 H -thi­eno[3,2- c ]pyrazole is presented in which the Jacobson reaction serves as the key step.",10.1055/s-0033-1338577,2013-11-28,0.5856409524425992
Tetrahedron,Synthesis of t-butyl and methyl peroxynitrate,,10.1016/s0040-4039(01)87614-0,1973-01-01,0.5856361796795522
Tetrahedron,"2-aza-1,3-dienes as novel precursors for the synthesis of -unsubstituted β-lactams. A three step synthesis of 4-acetoxy-3-phenoxy-2-azeridinone",,10.1016/s0040-4039(00)87894-6,1988-01-01,0.5856358554136774
Tetrahedron,"Woodfruticosin, an inhibitor of DNA topoisomerase II from kurz",,10.1016/s0040-4039(00)94563-5,1990-01-01,0.5856351132713338
Organic Letters,Synthesis of the Spirocyclic Core of the Prunolides Using a Singlet Oxygen-Mediated Cascade Sequence,"[reaction: see text] A highly efficient and rapid four-step synthesis of the bis-spiroketal core of the prunolide natural products, starting from furan itself, is described. The key step and culmination of the synthesis, responsible for zipping up the spirocyclic core, is a singlet oxygen-orchestrated cascade sequence in which a double photooxygenation of a 1,2-difuryl alkene precursor precedes dehydration and spirocyclization to furnish the intact prunolide core.",10.1021/ol050619b,2005-05-10,0.5856330573316149
Journal of Organic Chemistry,"Synthesis of Structurally Diverse 3-, 4-, 5-, and 6-Membered Heterocycles from Diisopropyl Iminomalonates and Soft<i>C</i>-Nucleophiles","Herein, we present a general synthetic strategy for the preparation of 3-, 4-, 5-, and 6-membered heterocyclic unnatural amino acid derivatives by exploiting facile Mannich-type reactions between readily available N-alkyl- and N-aryl-substituted diisopropyl iminomalonates and a wide range of soft anionic C-nucleophiles without using any catalyst or additive. Fully substituted aziridines were obtained in a single step when enolates of α-bromo esters were employed as nucleophiles. Enantiomerically enriched azetidines, γ-lactones, and tetrahydroquinolines were obtained via a two-step catalytic asymmetric reduction and cyclization sequence from ketone enolate-derived adducts. Finally, highly substituted γ-lactams were prepared in one pot from adducts obtained using acetonitrile-derived carbanions. Overall, this work clearly demonstrates the utility of iminomalonates as highly versatile building blocks for the practical and scalable synthesis of structurally diverse heterocycles.",10.1021/acs.joc.9b00681,2019-04-22,0.5856328009131603
Tetrahedron,Transesterification of trimethyl orthoacetate: an efficient protocol for the synthesis of 4-alkoxy-2-aminothiophene-3-carbonitriles,,10.1016/j.tetlet.2012.12.090,2012-12-31,0.5856308517638015
Journal of Organic Chemistry,Synthesis of Lactams via a Chiral Phosphoric Acid-Catalyzed Aniline Cyclization,"The enantioenriched lactams disclosed in this work are synthesized concisely in four steps. In the penultimate reaction, a benzylamine species complexes with a chiral phosphoric acid to produce benzo-fused δ-lactams equipped with an all-carbon quaternary stereocenter. Partial and full reductions were carried out on the ester and amide moieties, and a Suzuki-Miyaura cross-coupling expanded the molecule from the aromatic ring. Finally, our method was successful at a >1 g scale, indicating that the method has important practical use.",10.1021/acs.joc.4c01060,2024-08-09,0.585618739148656
Tetrahedron,"Competing pathways in the photonitrogenation of a 3,5-dihydro-4H/-1,2,3,-triazol-4-one. A novel route to aziridinones",,10.1016/s0040-4039(00)85686-5,1982-01-01,0.5856142176372919
European Journal of Organic Chemistry,First Total Synthesis of Piperenol B and Configuration Revision of the Enantiomers Piperenol B and Uvarirufol A,"Abstract We report herein the first total synthesis of piperenol B, a polyoxygenated cyclohexene derivative with reported pharmacological activity isolated from Piper cubeb . The chiral building block for this synthetic approach is derived from microbial cis‐ipso , ortho ‐dihydroxylation of sodium benzoate, which was optimized to the multi‐ten‐gram scale by reaction medium engineering. Final‐stage deprotection of an acetonide was investigated in detail, leading to an efficient eight‐step protocol for the synthesis of piperenol B with a total yield of 10 %. Most importantly, the previously assigned absolute configuration of piperenol B was revised and unequivocally established by 2D NMR analysis and the Mosher's ester method.",10.1002/ejoc.201403582,2015-01-27,0.5856134299157039
Tetrahedron,"Phacidin, a novel γ-pyrone fungal growth inhibitor from var",,10.1016/s0040-4039(01)92306-8,1974-01-01,0.5856086930527632
Journal of the American Chemical Society,"Dynamic Kinetic Asymmetric Transformation of Diene Monoepoxides:  A Practical Asymmetric Synthesis of Vinylglycinol, Vigabatrin, and Ethambutol","The ability to perform a dynamic kinetic asymmetric transformation (DYKAT) using the palladium-catalyzed asymmetric allylic alkylation (AAA) is explored in the context of butadiene monoepoxide. The versatility of this commercially available, but racemic, four-carbon building block becomes significantly enhanced via conversion of both enantiomers into a single enantiomeric product. The concept is explored in the context of a synthesis of vinylglycinol with phthalimide as the nitrogen source. The success of the project required a new design of the ligand for palladium wherein additional conformational restraints were introduced. Thus, the phthalimide derivative of vinylglycinol was obtained in nearly quantitative yield and had an ee of 98% which, upon crystallization, was enhanced to >99%. This one-step synthesis of a protected form of vinylglycinol provided short practical syntheses of the title compounds. Vigabatrin requires only four steps, and ethambutol six. The intermediate to the existing synthesis of ethambutol is available in 87% yield in three steps. (R )-Serine derives from oxidative cleavage of the double bond. The reaction of phthalimide and isoprene monoepoxide demonstrates the remarkable ability of the chiral ligands to control both regioselectivity and enantioselectivity and demonstrates the effectiveness of this protocol in creating a quaternary center asymmetrically.",10.1021/ja000547d,2000-06-01,0.5856023857890249
Journal of Organic Chemistry,"De Novo Synthesis of a Methylene-Bridged Neu5Ac-α-(2,3)-Gal <i>C</i>-Disaccharide","A general strategy toward the synthesis of C-ketosides of N-acetylneuraminic acid (Neu5Ac) has been developed and successfully applied to the synthesis of methylene-bridged Neu5Ac-alpha-(2,3)-Gal C-disaccharide 2. The key strategic element of this novel approach is a stereoselective, 6-exo-trig selective, electrophilic cyclization of the appropriate open chain precursor 4 by means of phenylselenyl triflate. The open chain precursor was formed by the addition of lithiated iodide 18 accessible from D-galactose to open chain aldehyde 5a obtained from D-glucono-delta-lactone by chain elongation. Subsequent C1-incorporation using Tebbe-reagent, formation of a cyclic carbonate, and deprotection of the two isopropylidene ketals afforded tetrol 4 which, upon treatment with phenylselenyl triflate, was stereoselectively cyclized in a 6-exo-trig selective manner. A selena-Pummerer rearrangement, oxidation, and esterification readily led to methyl ester 37 which, after deacetylation, could be regioselectively tetrabenzoylated with benzoyl cyanide. Triflate activation of the axial hydroxyl group in 40 and nucleophilic displacement by azide ion with inversion of configuration afforded azide 41, which was reduced with hydrogen and Pearlman's catalyst. Concomitant removal of the benzyl ethers and subsequent saponification of all ester moieties successfully completed the de novo synthesis of the desired methylene bridged Neu5Ac-alpha-(2,3)-Gal C-disaccharide 2.",10.1021/jo015543l,2001-05-12,0.5855899877829708
Journal of Organic Chemistry,"Efficient Diastereoselective Synthesis of Trifarane-Type Sesquiterpenes, Trifarienols A and B","Diastereoselective total synthesis of trifarienols A and B, trifarane-type sesquiterpenes isolated from the Malaysian Cheilolejeunea trifaria, was achieved via an intramolecular Hosomi-Sakurai reaction of the aldehyde to construct a substituted bicyclo[3.3.1]nonane skeleton having the exo-methylene moiety of the target compounds in one step.",10.1021/jo900369t,2009-03-31,0.585587422002434
Tetrahedron,Palladium-catalyzed asymmetric alkylation via π-allyl intermediate: Acetamidomalonate ester as a nucleophile.,,10.1016/s0040-4039(00)97803-1,1990-01-01,0.5855841954275186
Tetrahedron,Photolysis of 4-substituted-4-hydroxy-3-cyclobuten-1-ones: a new route to butenolides from 4-hydroxycyclobutenones,,10.1016/0040-4039(88)85284-5,1988-01-01,0.5855833369600535
Organic Letters,"One-Pot Construction of Indolo[2,3-<i>b</i>]quinoxalines through Ruthenium-Catalyzed <i>Ortho</i> C–H Bond Functionalization of 2-Arylquinoxalines with Sulfonyl Azides","The synthesis of N-substituted indolo[2,3- b ]quinoxalines has been developed through a Ru(II)-catalyzed ortho C–H functionalization of 2-arylquinoxalines with sulfonyl azides and further oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone in one pot. This double C–N bond formation strategy provides a new efficient route for the preparation of a series of biologically relevant 6 H -indolo[2,3- b ]quinoxaline derivatives in up to 94% yield, suggesting a broad substrate scope applicability. The preliminary mechanistic studies reveal that the sequential C–N bond formations proceed through the formation of a five-membered ruthenacyclic intermediate in the first step and a radical mechanism in the second step.",10.1021/acs.orglett.1c02837,2021-09-20,0.5855795815800604
Journal of Organic Chemistry,Studies toward the Synthesis of Vinigrol. First Construction of the Tricyclic Ring System,"The first synthesis of a functionalized tricyclic skeleton of vinigrol is described. The key step involved an anionic oxy-Cope rearrangement of bicyclic allylic alcohol 18, readily prepared by highly stereoselective addition of vinyl magnesium chloride to the hydroxy enone 15b . Introduction of the tertiary hydroxy group at carbon 8a was achieved by an unexpected hydration of 30 with aqueous trifluoroacetic acid.",10.1021/jo970343o,1997-07-01,0.5855784903788647
Synthesis,Stereoselective Total Synthesis of <i>iso</i>-Cladospolide B,"A simple and efficient stereoselective total synthesis of iso-cladospolide B and a formal total synthesis of cladospolide B, using Jacobsen’s hydrolytic kinetic resolution, is described.",10.1055/s-2006-950317,2006-12-01,0.5855784042356088
Journal of the American Chemical Society,"Total Synthesis of the Norcembranoid Scabrolide B and Its Transformation into Sinuscalide C, Ineleganolide, and Horiolide","It was recognized only recently that the sister norcembranoids scabrolides A and B have notably different carbotricyclic scaffolds. Therefore, our synthesis route leading to scabrolide A could not be extended to its sibling. Rather, a conceptually new approach had to be devised that relied on a challenging intramolecular alkenylation of a ketone to forge the congested central cycloheptene ring at the bridgehead enone site; the required cyclization precursor was attained by a lanthanide-catalyzed Mukaiyama-Michael addition. The dissonant 1,4-oxygenation pattern was then installed by allylic rearrangement/oxidation of the enone, followed by suprafacial 1,3-transposition. Synthetic scabrolide B was transformed into sinuscalide C by dehydration and into ineleganolide by base-mediated isomerization/oxa-Michael addition, which has potential biosynthetic implications; under basic conditions, the latter compound converts into horiolide by an intricate biomimetic cascade.",10.1021/jacs.4c09467,2024-08-21,0.5855723159228865
Angewandte Chemie International Edition,A Short Enantioselective Total Synthesis of (−)‐Englerin A,"Selective oxidations of dienone 2 as well as a ring-closing metathesis to give the hydroazulene framework enabled the 12-step preparation of title compound 1 from (−)-photocitral A (3), which is in turn rapidly available from (−)-isopulegol through dual catalysis.",10.1002/anie.201301247,2013-04-15,0.5855710604973338
Tetrahedron,Cyclization of olefinic β-ketoesters. A novel synthesis of Δ8(14)-podocarpen-13-one,,10.1016/s0040-4039(00)77901-9,1976-02-01,0.5855709640956077
Tetrahedron,Hydrogenations of triacetic acid lactone. A new synthesis of the carpenter bee ( ) sex pheromone,,10.1016/s0040-4039(01)85553-2,1980-01-01,0.5855673437083508
Journal of Organic Chemistry,"An Improved Synthesis of (−)-5,11-Dideoxytetrodotoxin","We describe an improved synthesis of (-)-5,11-dideoxytetrodotoxin from an enone, which was used for synthesis of tetrodotoxin and its analogues in this laboratory. One of the major modifications was to establish a two-step guanidinylation of trichloroacetamide of a highly functionalized intermediate, which allowed us to prepare (15)N(2)-labeled 5,11-dideoxytetrodotoxin for biosynthetic investigations.",10.1021/jo302773f,2013-01-16,0.5855623526252933
Synlett,Synthesis of a Mesogenic Compound with a Defined Conformation,"All articles of this category The synthesis of the bicyclohexyl derivative 2 has been attained in 4 steps by bi-directional elaboration of bicyclohexanone 3 . Due to the specifically placed methyl substituents, 2 populates a single conformation at the inter-ring bond, resulting in improved material properties. carbocycles - conformation - fluorine - liquid crystals",10.1055/s-2001-14633,2001-01-01,0.5855592863459673
Organic Letters,Asymmetric [2 + 2] Cycloaddition:  Total Synthesis of (−)-Swainsonine and (+)-6-Epicastanospermine,"[reaction: see text] An asymmetric total synthesis of (-)-swainsonine and (+)-6-epicastanospermine is described from a common intermediate, which is obtained through diastereoselective [2 + 2] cycloaddition of dichloroketene to a chiral enol ether.",10.1021/ol0617751,2006-09-13,0.5855578182266611
Synthesis,O-Pyrazolylpropynyl-Hydroxylamines as Versatile Intermediates in the Synthesis of Compounds of Pharmacological Interest,"Through an optimised Pd/Cu-catalysed cross-coupling reaction of 4-iodopyrazoles with 2-propyn-1-ol, followed by Mitsunobu transformation with N-hydroxyphthalimide and subsequent hydrazinolysis, O-[(pyrazol-4-yl)-prop-2-ynyl]-hydroxylamines were obtained in good yields. Their usefulness as intermediates in the synthesis of pharmaceuticals is exemplified by the first reported intramolecular cyclization of O-(2-propynyl)-hydroxylamines to yield 4,5-dihydro-isoxazoles.",10.1055/s-2001-16768,2001-01-01,0.5855553835330641
Journal of the American Chemical Society,Enantioselective Total Synthesis of (−)-Incarviatone A,We report herein the first total synthesis of (-)-incarviatone A (1) in 14 steps starting from commercially available inexpensive phenylacetic acid (9). Our early stage synthesis relies on the scalable and sequential C-H functionalization to rapidly assemble the indanyl dialdehyde framework. Further biomimetic cascade strategy allows us to obtain the natural product in a one-pot operation. We also conduct detailed mechanistic studies and disclose all the possible intermediates and isomers formed during the biomimetic cascade process.,10.1021/jacs.5b08551,2015-09-15,0.5855540194270548
European Journal of Organic Chemistry,Synthesis of Regioisomeric Pyrido[<i>c</i>]azocanones from Azaindanone Derivatives,"Abstract A ring enlargement reaction with methylamine gave new pyrido[2,3‐ c ]‐, pyrido[3,4‐ c ]‐ and pyrido[3,2‐ c ]azocanone derivatives from cyclic β‐oxo esters with a cyclopentapyridine skeleton and a 1,4‐diketone moiety. The starting materials for this ring transformation were either prepared from halogenopyridine carboxylates by Heck reaction and subsequent hydrogenation, or (halogenomethyl)pyridine carboxylates were submitted to S N reaction with diethyl malonate. Both routes were completed by Dieckmann condensation to build the cyclic β‐oxo ester structure and alkylation with phenacylbromide to install the 1,4‐diketone motif.",10.1002/ejoc.201301736,2014-02-03,0.5855523830470352
Organic Letters,Stereoselective Approach to Hydroxyindolizidines:  Protection/Deprotection of the Nitrone Functionality via Cycloaddition/Retrocycloaddition,"The enantiomerically pure indolizidine (-)-21 has been synthesized starting from L-malic acid. The key intermediate 20 has been assembled through an intramolecular 1,3-dipolar cycloaddition of a nitrone generated in situ by retrocycloaddition from isoxazolidine 17 or 18. The configuration of the new three stereocenters was set up with complete control in the cycloaddition step. The presented synthetic route provides a general and highly selective methodology toward indolizidines having the [1,8a]-cis configuration.",10.1021/ol006125q,2000-07-12,0.5855485799132475
Tetrahedron,Highly efficient palladium-catalyzed cross-coupling of diarylborinic acids with arenediazoniums for practical diaryl synthesis,,10.1016/j.tetlet.2019.151491,2019-12-07,0.5855476338848244
Angewandte Chemie International Edition,Total Synthesis of Quinoxapeptin A-C: Establishment of Absolute Stereochemistry,"The relative and absolute stereochemistry of the naturally occurring potent HIV reverse transcriptase (RT) inhibitors 1 and 2, quinoxapeptin A and B, were established by total synthesis. Their synthetic precursor 3 (dubbed quinoxapeptin C) was found to be a more potent HIV-1 RT inhibitor and to lack the potent cytotoxic activity characteristic of 1 and 2.",10.1002/(sici)1521-3773(19990816)38:16<2424::aid-anie2424>3.0.co;2-9,1999-08-16,0.585531816936899
Organic Letters,Total Synthesis of (±)-Paeonilide,"The total synthesis of paeonilide, a natural anti-PAF (platelet-activating factor) new skeleton monoterpenoid with an IC(50) value of 8 microg/mL, was achieved in 16 steps with 15% overall yield from commercially available 2-hydroxy-4-methylacetophenone. [reaction: see text]",10.1021/ol060382z,2006-05-09,0.5855316840389729
Synthesis,"One-Pot Synthesis of 1,4,7,10,13,16,21,24-Octaazabicyclo[8.8.8]hexacosane - The Peraza Analogue of [2.2.2]Cryptand","The peraza analogue of polyether cryptand [2.2.2], 1,4,7,10,13,16,21,24-octaazabicyclo[8.8.8]hexacosane, has been synthesized in 70% yield via a two-step one-pot procedure by the condensation of tris(2-aminoethyl)amine (tren) with glyoxal in isopropanol at -78 °C followed by reduction of the intermediate with Na/liquid NH3. This preparation is significantly faster, simpler, and higher yielding than the previously reported two-step procedure, with its lengthy isolation process and 45% overall yield.",10.1055/s-2006-926335,2006-01-01,0.5855310905765609
Journal of Organic Chemistry,Highly Enantioselective Intermolecular Cu(I)-Catalyzed Cyclopropanation of Cyclic Enol Ethers. Asymmetric Total Synthesis of (+)-Quebrachamine,"A set of cyclic enol ethers derived from 2,3-dihydrofuran 35 and 3,4-dihydropyran 8 with a varying substitution pattern at the olefinic system were synthesized. Evans's ligand 5 with Cu(I)OTf was found to be an effective catalyst in the cyclopropanation reaction between cyclic enol ethers 14, 19, 28-31, and 33 and ethyl diazoacetate 6 to give diastereoselectivities up to exo/endo = 95:5 and enantioselectivities higher than 95% in nearly all cases. Because of the selective building of a quarternary carbon center and good yields in the formation of bicyclic structures 34c-h, the reaction was used as a key step in the asymmetric synthesis of (+)-quebrachamine 7, an indole alkaloid of the Aspidosperma family. After acid-induced ring opening of bicyclic compound 34f to lactone 40 followed by LiAlH(4) reduction to the masked aldehyde 41, a reaction with tryptamine gave intermediate 42. This alcohol was efficiently converted into the indole alkaloid (+)-quebrachamine 7 in an overall yield of 37% starting from the chiral synthon 34f. Moreover it revealed the absolute configuration of the quarternary center of the cyclopropanation product 34f to be S.",10.1021/jo9807417,1998-08-01,0.5855308847604189
Tetrahedron,"Enantioselective synthesis of NK-1 receptor antagonists (+)-CP-99,994 and (+)-CP-122,721",,10.1016/s0040-4039(02)01832-4,2002-10-01,0.5855293250136203
Tetrahedron,Selective functionalization of cavitands: synthesis of a new hemicarcerand,,10.1016/s0040-4039(00)92093-8,1992-06-01,0.5855292874591224
Organic Letters,Enantioselective Synthesis of Guaianolides in the Osmitopsin Family by Domino Metathesis,"Relay metathesis enabled an improved access from (S)-citronellal to the marine trisnorguaiane (-)-clavukerin A. This hydroazulene was applied as an advantageously functionalized building block for the asymmetric synthesis of the sesquiterpene lactone osmitopsin and the proposed structure of 4,5-epoxyosmitopsin using a chemo-, regio-, and diastereoselective diepoxide opening as the key step.",10.1021/acs.orglett.6b01619,2016-06-22,0.5855226653082435
Tetrahedron,"DAST promotes the synthesis of new 5-(trifluoromethyl)-3-(1,1-difluoroethan-2-yl)-1H-pyrazoles",,10.1016/j.tetlet.2009.01.005,2009-01-11,0.5855183637451105
Tetrahedron,An efficient asymmetric spiroannulation process,,10.1016/s0040-4039(01)89008-0,1989-01-01,0.5855181604418161
Green Chemistry,Comparing the greenness and sustainability of three routes to an HIV protease inhibitor intermediate,The greenness and sustainability of three different routes for the synthesis of an advanced intermediate for a group of HIV protease inhibitors used in antiretroviral (ARV) therapy are compared.,10.1039/d1gc00986a,2021-01-01,0.5855176022085056
Angewandte Chemie International Edition,"Biomimetic Synthesis of 5,6‐dihydro‐glaucogenin C: Construction of the Disecopregnane Skeleton by Iron(II)‐Promoted Fragmentation of an α‐Alkoxy Hydroperoxide","A skeleton key: A biomimetic synthesis of the title natural product was completed in 19 steps and 6.4 % overall yield. Iron(II)-promoted fragmentation of α-alkoxy hydroperoxide and subsequent trapping of the resulting tertiary carbon radical by iodide enabled the highly efficient construction of the challenging 13,14:14,15-disecopregnane skeleton (see scheme; TBDPS=tert-butyldiphenylsilyl).",10.1002/anie.201101893,2011-06-17,0.5855150116971374
Synthesis,Synthesis of<i>N</i>-Substituted Muscimol Derivatives Including<i>N</i>-Glycylmuscimol,"All articles of this category The preparation of museimol (a potent but toxic GABA neurotransmitter agonist), from dimethyl acetylenedicarboxylate via methyl 3-hydroxyisoxazole-5-carboxylate and the corresponding amide, has been improved and extended to a general synthesis of N -alkyl and N,N -dialkyl derivatives. The efficient route to muscimol itself [muscimol itself costs 60 -170 DM/10 mg] has enabled a study of its chemistry to be undertaken, a first result of which is its incorporation into a peptide, i.e. the preparation of N -glycylmuscimol.",10.1055/s-1985-31439,1985-01-01,0.5855104345492047
Journal of Organic Chemistry,"Silver-Mediated Intermolecular [2 + 2 + 1] Cyclization of Terminal Alkynones with Elemental Selenium: Regioselective Synthesis of 2,4- or 3,4-Dicarbonylselenophenes","An efficient and atom-economical silver-mediated [2 + 2 + 1] cyclization protocol for the selective synthesis of 2,4- or 3,4-dicarbonylselenophenes has been developed. Readily accessible substrates, commercially available elemental selenium, and good functional group tolerance make this procedure attractive for the selective synthesis of dicarbonylselenophenes. Preliminary mechanistic investigations indicated that silver acetylene species are possible intermediates for the formation of 3,4-dicarbonylselenophenes.",10.1021/acs.joc.3c01438,2023-10-13,0.5855097688338093
Tetrahedron,Diastereoselectivity in the Synthesis of 3(2H)-Furanones. Total Synthesis of (+)-Muscarine,,10.1016/s0040-4039(00)99571-6,1989-01-01,0.5855043883217635
Synthesis,Site-Specific Synthesis of Carbazole Derivatives through Aryl Homocoupling and Amination,"We synthesized various carbazoles from anilines through a three-step process with good overall yields (up to 48%). This process comprises N-acetylation, copper(0)-mediated Ullmann homocoupling, and acid-mediated intramolecular amination. It permits various functional­ groups on the substrate. Scale-up of the developed three-step synthetic route to carbazoles was also demonstrated.",10.1055/s-0039-1690759,2019-11-26,0.5854978186525429
Tetrahedron,"FK-506 synthetic studies. 3. An efficient asymmetric synthesis of the C(24)–C(34) fragment of FK-506, FR-900520, and FR-900523",,10.1016/s0040-4039(01)93398-2,1989-01-01,0.5854921607473095
Journal of Organic Chemistry,Scalable Synthesis of <i>N</i>-Acylaziridines from <i>N</i>-Tosylaziridines,"N-Acylaziridines are important starting materials for the synthesis of chiral amine derivatives. The traditional methods for producing these activated aziridines have significant drawbacks. The gram scale synthesis of N-acylaziridines by deprotection of N-tosylaziridines and reprotection with N-hydroxysuccinimide derivatives is described. Mono- and disubstituted aziridines perform well, with complete retention of stereochemical purity. The consistently moderate yields are linked to the N-tosylaziridine deprotection step, while acylation with N-hydroxysuccinimide derivatives is highly efficient.",10.1021/jo401267j,2013-08-14,0.5854854569193344
Synlett,A New Strategy for the Diastereoselective Synthesis of Polyfunctionalized Pyrrolidines,"This paper describes a new strategy for the synthesis of polyfunctionalized pyrrolidines via the ring-closing metathesis ­reaction of substituted 3-allyl-4-vinyl-2-oxazolindones and sub­sequent diastereoselective cis-dihydroxylation of the resulting ­pyrrolo[1,2-c]oxazol-3-ones.",10.1055/s-2003-43362,2004-01-01,0.5854841222763701
Organic Letters,General Synthesis of Highly Functionalized Cyclopentane Segments for the Preparation of Jatrophane Diterpenes,"Short and efficient syntheses of two diastereomeric cyclopentane segments present in most jatrophane diterpenes were achieved. Key steps are a stereoselective C-2 elongation, an RCM, and a hydroboration reaction. An orthogonal protecting group methodology makes these segments useful building blocks for diterpene synthesis.",10.1021/ol902221y,2009-10-26,0.5854838642109446
Synlett,Evolution of a Cycloaddition–Rearrangement Approach to the Squalestatins: A Quarter-Century Odyssey,"The highs, lows, and diversions of a journey leading to two syntheses of 6,7-dideoxysqualestatin H5 is described. Both syntheses relied on highly diastereoselective n-alkylations of a tartrate acetonide enolate and subsequent oxidation–hydrolysis to provide an asymmetric entry to β-hydroxy-α-ketoester motifs. The latter were differentially elaborated to diazoketones which underwent stereo- and regioselective Rh(II)-catalysed cyclic carbonyl ylide formation–cycloaddition and then acid-catalysed transketalisation to generate the 2,8-dioxabicyclo[3.2.1]octane core of the squalestatins/zaragozic acids at the correct tricarboxylate oxidation level. The unsaturated side chain was either protected with a bromide substituent during the transketalisation or introduced afterwards by a stereoretentive Ni-catalyzed Csp3–Csp2 cross-electrophile coupling. 1 Introduction 2 Racemic Model Studies to the Squalestatin/Zaragozic Acid Core 3 Asymmetric Model Studies to a Keto α-Diazoester 3.1 Dialkyl Squarate Desymmetrisation 3.2 Tartrate Alkylation 3.2.1 Further Studies on Seebach’s Alkylation Chemistry 4 Failure at the Penultimate Step to DDSQ 5 Second-Generation Approach to DDSQ: A Bromide Substituent Strategy 5.1 Stereoselective Routes to E-Alkenyl Halides via β-Oxido Phosphonium Ylides 5.2 Back to DDSQ Synthesis 6 An Alternative Strategy to DDSQ: By Cross-Electrophile Coupling 7 Alkene Ozonolysis in the Presence of Diazo Functionality: Accessing α-Ketoester Intermediates 8 Summary",10.1055/s-0040-1707127,2020-06-04,0.5854736725015462
Synthesis,Studies Towards the Synthesis of the C(9)-C(20) Lactone-Dipropionate Fragment of Calyculin C,In this paper we describe the synthesis of a diastereomer of the C(9)-C(20) dipropionate-lactone fragment of Calyculin C. A short and enantioselective synthesis of the key intermediate 2 has been developed. This intermediate will play a critical role also in the synthesis of the correct diastereomer of C(9)-C(20) dipropionate-lactone fragment of Calyculin C.,10.1055/s-2004-822389,2004-01-01,0.5854710726359579
Tetrahedron,Diastereoselective radical cyclization of bromoacetals: Efficient synthesis of (±)-botryodiplodin,,10.1016/s0040-4039(99)00487-6,1999-04-01,0.5854566225078143
European Journal of Organic Chemistry,An Improved Biomimetic Formal Synthesis of Abyssomicin C and <i>atrop</i>‐Abyssomicin C,"Biomimetic approaches towards the synthesis of abysssomicin C and atrop ‐abyssomicin C are based on a powerful intramolecular Diels–Alder reaction (IMDA) of a butenolide derivative attached to a keto‐triene side chain, where the stereogenic centers and the carbon framework are established in one step. The synthesis of the IMDA precursor is based on an ionic coupling of methyl γ‐methylene‐β‐tetronate with various aldehydes. However, the low yields of the coupling and the high sensitivity of the precursor hampered the efficiency of the developed routes and should be met. In the present work, a modified aldehyde is coupled with methyl γ‐methylene‐β‐tetronate, in a substantially higher yield. Asymmetric synthesis of this aldehyde is based on the use of the widely available and cheap Amano lipase AK. In addition, the development of a highly convenient one‐pot oxidation‐IMDA reaction protocol obviates the isolation of the sensitive IMDA‐precursor and augments the yield towards the carbocyclic skeleton of abysssomicin C and atrop ‐abyssomicin C.",10.1002/ejoc.202000671,2020-07-10,0.5854546470074818
Tetrahedron,Remarkably chemoselective indium-mediated coupling en route to the C21–C40 acyclic portion of the azaspiracids,,10.1016/s0040-4039(00)02157-2,2001-01-01,0.5854468638702405
Journal of Organic Chemistry,Stereoselective Pd-Catalyzed Synthesis of Quaternary α-<scp>d</scp>-<i>C</i>-Mannosyl-(<i>S</i>)-amino Acids,"In this paper, we report the stereoselective synthesis of α-D-C-mannosyl-(S)-amino acids exploiting, as a key step, an allylic alkylation of glycal-derived π-allyl Pd(II) intermediates, prepared by oxidative addition of Pd(0) species to 2,3-unsaturated pyranosides (pseudoglycals). The reaction of 4,6-di-O-acetyl α-pseudoglucal carbonate 10a with racemic alanine-, valine-, and phenylalanine-derived azlactones gave the corresponding (4S)-4-α-D-C-mannosyl-2-phenyloxazol-5(4H)-ones as the major diastereoisomers in high yields. The final α-D-C-mannosyl-(S)-amino acids were obtained in a few steps comprising highly diastereoselective dihydroxylation of the glucal derivative double bond followed by the one-pot hydrolysis of the benzamido and acetate protecting groups. Main features of this method are the conciseness of the synthetic sequence, the high diastereoselection of the allylic alkylation step, the use of racemic α-amino acids as starting material, and the good overall yields.",10.1021/jo2002962,2011-05-19,0.5854461621969994
Journal of Organic Chemistry,Stereoselective Divergent Synthesis of Four Diastereomers of Pachastrissamine (Jaspine B),"A divergent short synthesis of four diastereomers of pachastrissamine was achieved. Natural pachastrissamine was synthesized through bis-tosylation of the common intermediate and cyclization. 2-epi-Pachastrissamine was obtained by monotosylation and spontaneous cyclization of D-ribo-phytosphingosine derivative. By use of regio- and stereospecific ring-opening reaction of the orthoester assisted by a Boc group as a key step, 3-epi- and 2,3-epi-pachastrissamines were synthesized. The three stereogenic centers of all the diastereomers were constructed by using Garner's aldehyde as the sole chiral source.",10.1021/jo1005284,2010-04-21,0.5854429208585191
Journal of Organic Chemistry,"NBS-Promoted Synthesis of Thiocyanated Aminomaleimides and Site-Selective Intramolecular Cyclization Access to 1,4-Benzothiazepines via S–CN Bond Cleavage","A transition metal-free concise and efficient protocol for the synthesis of thiocyanated aminomaleimides and benzo[ e ][1,4]thiazepine derivatives has been developed. The method involves an initial α-C–H thiocyanation of aminomaleimides with KSCN and TEMPO-mediated tandem S–CN bond cleavage/intramolecular cyclization substitution processes, which enables the formation of seven-membered S/N-heterocycles. This synthetic strategy provides a reliable method for the synthesis of biologically interesting benzo[ e ][1,4]thiazepine derivatives by using KSCN as sulfur sources as well as expands the application of enaminones thiocyanation reactions in heterocycles synthesis.",10.1021/acs.joc.3c02607,2024-04-09,0.5854422223900396
Tetrahedron,"Synthesis of the new ring system 6,8-dihydro-5H-pyrrolo[3,4-h]quinazoline",,10.1016/j.tetlet.2009.07.045,2009-07-13,0.585433719193368
Tetrahedron,A formal convergent synthesis of (+)-trans-solamin,,10.1016/j.tetlet.2008.01.046,2008-01-16,0.5854241759093732
Tetrahedron,Chemical synthesis of hormone receptor probes: high affinity photoactivated enediyne-estrogens,,10.1016/s0040-4039(01)01902-5,2001-12-01,0.5854235640203018
Journal of Organic Chemistry,Stereoselective Synthesis of a Thymine Derivative of (<i>S</i>)-2-Hydroxy-4-(2-aminophenyl)butanoic Acid. A Novel Building Block for the Synthesis of Aromatic Peptidic Nucleic Acid Oligomers<sup>1</sup>,"The synthesis of a thymine derivative of ( S )-2-hydroxy-4-(2-aminophenyl)butanoic acid, compound 1, was achieved in high enantiomeric purity. The acyclic pyrimidine analog ( S )- 1 is a useful building block for the synthesis of a novel class of oligomers, the aromatic peptide nucleic acids (APNA, Scheme 1). The APNA tetramer 18 was prepared from the amino acid monomer ( S )- 1 using classical peptide synthesis. UV absorption spectra and 1 H NMR data of this tetramer suggested that base stacking interactions in the APNA oligomers may be favorable.",10.1021/jo962326p,1997-08-01,0.5854197871214559
Tetrahedron,"The synthesis and evaluation of 12,13-benzodesoxyepothilone B: a highly convergent route","The title compound retains some of the affinity for microtubule assemblies as does 12,13-desoxyepothilone B.",10.1016/s0040-4039(99)01433-1,1999-09-01,0.5854137151444847
Tetrahedron,"PEG-embedded thiourea dioxide (PEG.TUD) as a novel organocatalyst for the highly efficient synthesis of 3,4-dihydropyrimidinones",,10.1016/j.tetlet.2010.10.124,2010-10-31,0.5854134600983317
Tetrahedron,Vicinal dianions of diethyl α-aroylsuccinates: a general synthetic route to α-aroyl- and α-arylidene-γ-butyrolactones,,10.1016/s0040-4039(03)01622-8,2003-08-01,0.585410262421197
Tetrahedron,"A convenient and improved synthesis of dithieno[3,2-b:2′,3′-d]thiophene",,10.1016/s0040-4039(02)00006-0,2002-02-01,0.5854044821060579
Synlett,Development of a Divergent Route to Erythrina Alkaloids,"Erythrina alkaloids were identified at the end of the 19th century and today, more than 100 members of the erythrinane family have been isolated. They are characterized by a unique tetracyclic, α-tertiary spiroamine scaffold. Herein we detail our efforts towards the development of a divergent enantioselective synthesis of (+)-dihydro-β-erythroidine (DHβE) – one of the most prominent members of this intriguing family of natural products. 1 Introduction 2 Synthetic Strategy 2.1 First Generation 2.2 Second Generation 2.3 Third Generation 2.3.1 Radical Endgame 2.3.2 Completion of the Total Synthesis 3 Conclusion",10.1055/s-0039-1690792,2020-01-23,0.5853978053551547
European Journal of Organic Chemistry,A Straightforward Approach to the Synthesis of Disubstituted Cyclopentenones,"In this paper we describe an approach for the synthesis of a set of new diversely di‐substituted cyclopentenones using Morita–Baylis–Hillman (MBH) adducts as building blocks. The synthesis was performed with few steps, but the overall yield reached 34 %. A key step of this approach is a rhodium mediated 1,4‐addition reaction on adequately functionalised MBH adducts, which leads to the creation of cinnamate ester derivatives with high E selectivity. These intermediates were used as substrates for an intramolecular Friedel‐Crafts cyclisation reaction to achieve the required 2,3‐substituted cyclopentenones. As far as we know, this is the first report to describe the synthesis of substituted cyclopentenones that directly employ MBH adducts as building blocks.",10.1002/ejoc.201901850,2020-01-25,0.5853945942789295
Organic Letters,"Total Synthesis of (+)-Condylocarpine, (+)-Isocondylocarpine, and (+)-Tubotaiwine","The first enantioselective total syntheses of indole alkaloids of the condylocarpine type are reported. (+)-Condylocarpine, (+)-isocondylocarpine, and (+)-tubotaiwine were prepared in high enantiomeric purity (er > 99:1) from (1S,5R)-hexahydro-1,5-methano-1H-azocino[4,3-b]indole-12-one 7b by way of five or six isolated intermediates.",10.1021/ol102709s,2010-12-06,0.5853865466412796
European Journal of Organic Chemistry,Synthetic Investigation toward the D‐Ring‐Functionalized Cytotoxic Oleanane‐Type Saponins Pithedulosides D and E,"Leveraging on the orchestrated application of both Schmidt and Yu glycosylations, the first total syntheses of the echinocystic acid saponins pithedulosides D and E, the two antitumoral and representative D‐ring‐functionalized oleanane‐type saponins, were achieved. Benefitting from the applied convergent synthetic strategy, the echinocystic acids could be synthesized in overall yields of as high as 71 and 76 % through four linear steps.",10.1002/ejoc.201700707,2017-06-09,0.5853862847485749
Tetrahedron,Bis-monensin: Synthesis of new chiral receptor from naturally occurring monensin ionophore,,10.1016/s0040-4039(00)97234-4,1990-01-01,0.5853857298264011
Tetrahedron,"Allenes and acetylenes XXVI. Organocuprate reactions of 1,3-alkadien-2-yl phosphates. a new approach to the synthesis of allenes",,10.1016/s0040-4039(00)81639-1,1983-01-01,0.5853826534997764
Organic Letters,Divergent Asymmetric Synthesis of Chiral Spiroheterocycles through Pd-Catalyzed Enantio- and Diastereoselective [3 + 2] Spiroannulation,"The palladium-catalyzed divergent asymmetric synthesis of chiral spiro-furanindoline derivatives is described. The zwitterionic alkoxy π-allyl Pd(II) intermediate, generated catalytically from vinyl ethylene carbonate (VEC), could undergo ligand-controlled enantio- and diastereoselective dipolar [3 + 2] spiroannulation with indole-based azadienes to afford the optically active spiro-furanindolines embedding an all-carbon quaternary stereocenter in high yields (up to 99%) with good to excellent stereoselectivities (up to 99% ee and up to >94:6 dr).",10.1021/acs.orglett.2c03643,2022-12-12,0.5853792542319403
Journal of Organic Chemistry,"Synthetic Study of 1,3-Butadiene-Based IMDA Approach to Construct a [5−7−6] Tricyclic Core and Its Application to the Total Synthesis of C8-<i>e</i><i>pi</i>-Guanacastepene O","An efficient intramolecular Diels-Alder (IMDA) strategy for the construction of the [5-7-6] tricyclic core (18) of guanacastepenes has been developed from cis- and trans-1,3-butadiene-tethered 4-oxopent-2-ynoic acid ethyl esters 10 and 11. This method facilitates the synthesis of C8-epi-guanacastepene O (36) in a very efficient manner.",10.1021/jo060996h,2006-08-10,0.5853707552001419
Angewandte Chemie International Edition,"A Modular Approach for Diversity‐Oriented Synthesis of 1,3‐<i>trans</i>‐Disubstituted Tetrahydroisoquinolines: Seven‐Step Asymmetric Synthesis of Michellamines B and C","Abstract 1,3‐ trans ‐Disubstituted tetrahydroisoquinoline (THIQ) is a common heterocyclic structural unit of naphthylisoquinoline alkaloids. The assembly of this structural unit is not trivial, which constitutes a substantial challenge in the total synthesis of naphthylisoquinoline alkaloids and related pharmaceuticals. Herein, we report a modular and convergent method for the rapid assembly of 1,3‐ trans ‐disubstituted THIQ frameworks through a three‐component Catellani reaction and a Au I ‐catalyzed cyclization/reduction cascade. With widely available simple aryl iodides, aziridines and (triisopropylsilyl)acetylene as the building blocks, this method paves a practical way for the diversity‐oriented synthesis of 1,3‐ trans ‐disubstituted THIQs. Based on this new method, concise syntheses of an analogue of the new drug mevidalen and four naphthylisoquinoline alkaloids have been accomplished, demonstrating the broad synthetic utility of this approach.",10.1002/anie.202205245,2022-05-26,0.5853698290122149
Synthesis,An Efficient Synthesis of Optically Pure N δ-Monomethylated l-Arginine and l-Ornithine,N ω -Methylated l -arginines such as asymmetric dimethyl- l -arginine (ADMA) and monomethyl- l -arginine (NMMA) are well-known endogenous modulators of the nitric oxide (NO) generating system. To understand the (patho)physiological role and impact of N δ -methylation of l -arginine and l -ornithine an efficient synthesis of the pure enantiomers was needed. A synthetic approach that furnished both the desired amino acids in 8–10 steps from commercially available N -Boc- l -ornithine in good overall yields (20–21%) and with high optical purity (>99% ee) is reported.,10.1055/s-0035-1561303,2016-01-05,0.5853650852325597
Synthesis,New Synthesis and Application of 3-Substituted Prolinols,Carbon skeleton of polysubstituted pyroglutamates with three contiguous asymmetric centers was built up in one base-induced coupling/cyclization reaction of α-sulfonylacetamide with 2-bromo-2-propenoates. A simple transformation to 3-substituted prolinols can be easily achieved via reduction and desulfonation. A ring expansion of prolinol has been used as the key step in the formal synthesis of isoguvacine and paroxetine. The one-pot conversion of 3-substituted prolinol to the 3-substituted pyroglutamic acid is also reported.,10.1055/s-2004-816001,2004-01-01,0.5853645961271011
Angewandte Chemie International Edition,Diversified Synthesis of Chiral Fluorinated Cyclobutane Derivatives Enabled by Regio‐ and Enantioselective Hydroboration,"The diversified synthesis of chiral fluorinated cyclobutane derivatives has remained a difficult task in synthetic chemistry. Herein, we present an approach for asymmetric hydroboration and formal hydrodefluorination of gem-difluorinated cyclobutenes through rhodium catalysis, providing chiral gem-difluorinated α-boryl cyclobutanes and monofluorinated cyclobutenes with excellent regio- and enantioselectivity, respectively. The key to the success of the two transformations relies on an efficient, mild and highly selective rhodium-catalyzed asymmetric hydroboration with HBPin (pinacolborane), in which the subsequent addition of a base, and a catalytic amount of palladium in some cases, results in the formation of formal hydrodefluorination products with the four-membered ring retained. The obtained chiral gem-difluorinated α-boryl cyclobutanes are versatile building blocks that provide a platform for the synthesis of enantioenriched fluorinated cyclobutane derivatives to a great diversity.",10.1002/anie.202401451,2024-04-02,0.5853591421700335
Tetrahedron,Novel synthetic routes suitable for constructing benzopyrone combinatorial libraries,,10.1016/s0040-4039(99)00279-8,1999-03-01,0.5853507497964471
Tetrahedron,Practical selective monohydrolysis of bulky symmetric diesters,,10.1016/j.tetlet.2017.12.061,2017-12-23,0.5853491906745028
Synthesis,"A Facile Synthesis of Homologous 4,4′-Dialkanoic Acid Substituted 2,2′-Bipyridines","A convenient three-step synthesis has been developed to prepare a series of homologous 4,4′-dialkanoic acid substituted 2,2′-bipyridines from 4,4′-dimethyl-2,2′-bipyridine.",10.1055/s-2002-25768,2002-01-01,0.5853439504347308
Tetrahedron,"Efficient synthesis of unsymmetrical 1,4-disubstituted-2,3-diketopiperazines via tandem reductive amination–cyclization",,10.1016/s0040-4039(00)01565-3,2000-11-01,0.5853373793139862
Organic Process Research & Development,"A Practical, Efficient Synthesis of 1,1-Dioxo-hexahydro-1λ<sup>6</sup>-thiopyran-4-carbaldehyde","A practical, efficient, and scalable procedure for the preparation of 1,1-dioxo-hexahydro-1λ 6 -thiopyran-4-carbaldehyde is reported. Synthesis of this aldehyde was complicated by high aqueous solubility of the product and the intermediates. The isolation and purification of the aldehyde was accomplished by conversion to the crystalline bisulfite adduct.",10.1021/op800108s,2008-08-27,0.5853319412943557
European Journal of Organic Chemistry,Synthesis of Benzene and Pyridine 2′‐<i>C</i>‐Methyl‐<i>C</i>‐ribonucleosides and ‐nucleotides,"Abstract A general and modular synthesis of substituted benzene and pyridine 2′‐ C ‐methyl‐ C ‐ribonucleosides was developed. Benzyl‐protected haloaryl‐ C ‐nucleoside intermediates were prepared by the addition of bromo(het)aryllithium reagents to a protected lactone, followed by acetylation and reduction. These halogenated intermediates were further transformed by Pd‐catalysed cross‐couplings, aminations, or hydroxylations. The final deprotection was rather troublesome, and different procedures involving catalytic hydrogenation on Pd/C, or treatment with BCl 3 , were optimized for each derivative. The final C ‐nucleosides were also all converted into the corresponding NTPs. None of the C ‐nucleosides showed any activity in the HCV replicon assay, and none of the NTPs showed any significant inhibition of the HCV polymerase.",10.1002/ejoc.201501219,2015-11-17,0.5853225482619479
Angewandte Chemie International Edition,"Selective Formation of a Trisubstituted Alkene Motif by <i>trans</i>‐Hydrostannation/Stille Coupling: Application to the Total Synthesis and Late‐Stage Modification of 5,6‐Dihydrocineromycin B","Countless natural products of polyketide origin have an E-configured 2-methyl-but-2-en-1-ol substructure. An unconventional entry into this important motif was developed as part of a concise total synthesis of 5,6-dihydrocineromycin B. The choice of this particular target was inspired by a recent study, which suggested that the cineromycin family of antibiotics might have overlooked lead qualities, although our biodata do not necessarily support this view. The new approach consists of a sequence of alkyne metathesis followed by a hydroxy-directed trans-hydrostannation and a largely unprecedented methyl-Stille coupling. The excellent yield and remarkable selectivity with which the signature trisubstituted alkene site of the target was procured is noteworthy considering the rather poor outcome of a classical ring-closing metathesis reaction. Moreover, the unorthodox ruthenium-catalyzed trans-hydrostannation is shown to be a versatile handle for diversity-oriented synthesis.",10.1002/anie.201501608,2015-04-13,0.5853218240047199
Synlett,"Asymmetric Synthesis of Pyrrolizidines, Indolizidines and Quinolizidines via a Double Reductive Cyclisation Protocol","This account describes an overview of the asymmetric syntheses of pyrrolizidines, indolizidines and quinolizidines via a common double reductive cyclisation protocol. The highly diastereoselective conjugate addition of an enantiopure lithium amide to an α,β-unsaturated ester incorporating a terminal C=C bond installed the nitrogen-bearing stereogenic centre and was followed by enolate functionalisation to introduce the second olefinic functionality. Alternatively, conjugate addition to the corresponding α-alkenyl α,β-unsaturated ester followed by α-protonation of the intermediate enolate may also be used to access the cyclisation precursor. After oxidation of the two terminal olefinic units to give the corresponding dialdehyde, tandem hydrogenolysis/hydrogenation was employed to efficiently construct the azabicyclic core of each target molecule. This double reductive cyclisation strategy was successfully utilised in the syntheses of 13 azabicyclic alkaloids or closely related analogues. 1 Introduction 2 Asymmetric Syntheses of (–)-Isoretronecanol and (–)-Trachelanthamidine 3 Asymmetric Syntheses of (+)-Trachelanthamidine [(+)-Laburnine], (+)-Tashiromine and (+)-epi-Lupinine 4 Asymmetric Syntheses of (–)-Hastanecine, (–)-Turneforcidine and (–)-Platynecine 5 Asymmetric Syntheses of (–)-Macronecine, (–)-Petasinecine, (–)-1-epi-Macronecine, (+)-1-epi-Petasinecine and (+)-2-epi-Rosmarinecine 6 Conclusion",10.1055/s-0036-1590975,2017-08-08,0.5853181484496325
Tetrahedron,An efficient synthesis of α-aryl β-(N-tosyl)amino phosphonate derivatives from α-diazophosphonate,,10.1016/j.tetlet.2003.08.124,2003-10-15,0.5853174488560191
Tetrahedron,Practical total synthesis of 11-deoxydaunomycinone and the first total synthesis of 11-deoxydaunomycin,,10.1016/s0040-4039(00)96570-5,1987-01-01,0.585315759341528
Journal of Organic Chemistry,"Synthesis of Tetrahydroindolizino[8,7-<i>b</i>]indole Derivatives in the Presence of Fe(OTf)<sub>3</sub> or CF<sub>3</sub>SO<sub>3</sub>H through Intramolecular Dearomatization of Indole","We have developed a convenient synthesis of tetrahydroindolizino[8,7- b ]indole derivatives via intramolecular dearomatization of indole. Highly functionalized tetrahydroindolizinoindoles can be prepared in the presence of trifluoromethanesulfonic acid in good to excellent yields (up to >99% yield) with novel designed pyrrole-tethered indoles. The same products can also be synthesized through a mild Fe(OTf) 3 -catalyzed process in acceptable to good yields (up to 75% yield).",10.1021/acs.joc.0c02188,2020-10-30,0.5853129235936055
Angewandte Chemie International Edition,Synthesis of Oximidine II by a Copper‐Mediated Reductive Ene–Yne Macrocyclization,Holy macro! An intramolecular copper-mediated reductive Castro–Stephens reaction furnished a key macrocyclic triene intermediate for the total synthesis of oximidine II (see scheme). The total synthesis of the natural product was completed and the mechanism of this unprecedented key reaction was deduced.,10.1002/anie.201103081,2011-06-29,0.5853061537393002
Journal of the American Chemical Society,Asymmetric Total synthesis of Asperones A and B through Organocatalyzed Quinone [5 + 2] Cycloaddition,"The first asymmetric total synthesis of the anti-inflammatory polyketides asperones A ( 1 ) and B ( 2 ) has been accomplished. Key synthetic steps include a Diels–Alder and retro-Diels–Alder cascade to construct the poly substituted phenol, an Al-Salen-catalyzed asymmetric cyanosilylation to form the tertiary alcohol of gregatin A, and an organocatalyzed intermolecular [5 + 2] cycloaddition of p -quinone with electron-deficient alkenes to build the crucial [3.2.1] octane core of asperones A ( 1 ) and B ( 2 ).",10.1021/jacs.4c16252,2025-02-13,0.5853039402739477
Organic Letters,An Expeditious Nazarov Cyclization Strategy toward the Hydroazulene Core of Guanacastepene A,"The hydroazulene core of guanacastepene A has been synthesized in five steps from commercially available starting materials using a classical Nazarov cyclization to install the stereochemistry in the cyclopentanone diastereoselectively. In the presence or absence of Lewis bases, a hydroazulenone or a spirocyclic ketone generated via a novel Wagner-Meerwein rearrangement is obtained with excellent selectivity and yield.",10.1021/ol036433z,2004-01-27,0.5852985242673823
Tetrahedron,Synthesis of 2-substituted benzothiazoles via the Brønsted acid catalyzed cyclization of 2-amino thiophenols with nitriles,,10.1016/j.tetlet.2019.06.039,2019-06-22,0.5852967237773833
Journal of Organic Chemistry,Synthesis of the Aziridinomitosene Skeleton by Intramolecular Michael Addition of α-Lithioaziridines:  An Aromatic Route Featuring Deuterium as a Removable Blocking Group,"A convergent synthetic route to the 1,2-aziridinopyrrolo(1,2-a)indole 34 has been developed. Key features of this route include the deuterium kinetic isotope effect to block undesired indole lithiation during tin-lithium exchange from 27a to 30a, the intramolecular Michael addition to generate the enolate 31a, and conversion into 34 by trapping with phenylselenenyl chloride. Reductive cleavage of the N-trityl group in 34 allows access to tetracyclic aziridinomitosenes containing the aziridine N-H subunit. Reduction of the C(9) ester in 34 with LAH gives the primary alcohol 35 with the correct C(9), C(9a), C(10) oxidation state corresponding to the aziridinomitosenes, and deprotection of 34 affords 37.",10.1021/jo030223i,2004-01-15,0.5852950378765465
Journal of Organic Chemistry,Total Syntheses of Variolin B and Deoxyvariolin B<sup>1</sup>,"Two alternative synthetic routes have been developed for the preparation of variolin B and deoxyvariolin B. The strategy is based on the preparation of the core tricyclic ring common to all variolins, pyrido[3',2':4,5]pyrrolo[1,2-c]pyrimidine, followed by a palladium-catalyzed cross-coupling reaction to give the tetracyclic system.",10.1021/jo035332b,2003-11-22,0.5852937199155295
Organic Letters,"Gold-Catalyzed Cyclization of Allene-Substituted Malonate Esters:  Synthesis of <i>β</i>,<i>γ</i>-Unsaturated <i>δ</i>-Lactones","An efficient method for the preparation of beta,gamma-unsaturated delta-lactones has been developed. The starting materials for the synthesis of these compounds are allene-substituted malonates which undergo gold-catalyzed cyclization by means of nucleophilic attack of the ester moiety on the allene. It is worth mentioning that this is the first example where an ester group attacks as a nucleophile in a gold-catalyzed transformation of allenes.",10.1021/ol070793v,2007-04-28,0.5852918892813787
Tetrahedron,Alkylation of vinyl sulfones as a route to 2-alkylidene tetrahydrofurans,,10.1016/s0040-4039(99)00573-0,1999-05-01,0.585283696430494
Journal of Organic Chemistry,"Stereoselective Syntheses of the 2-Isopropenyl-2,3-dihydrobenzofuran Nucleus:  Potential Chiral Building Blocks for the Syntheses of Tremetone, Hydroxytremetone, and Rotenone","The first enantioselective synthesis of the 2-isopropenyl-2,3-dihydrobenzofuran skeleton of tremetone and hydroxytremetone from (E)-4-(2-hydroxyphenyl)-2-methyl-2-butenyl methyl carbonate and (E)-4-(2,6-dihydroxyphenyl)-2-methyl-2-butenyl methyl carbonate, respectively, is described. The key step is a catalytic palladium-mediated reaction in the presence of the chiral Trost ligand.",10.1021/jo062447h,2007-03-22,0.5852799577993483
Organic Letters,Synthesis of Azepinoindoles and Oxepinoindoles through Brønsted-Acid-Catalyzed Cyclization of an <i>In Situ</i> Generated Dihydrospiroquinoline Intermediate,"We have developed a straightforward and efficient synthetic protocol to produce 5,6,7,12-tetrahydrobenzo[2,3]azepino[4,5- b ]indole and 7,12-dihydro-6 H -benzo[2,3]oxepino[4,5- b ]indole derivatives under mild conditions. This annulation process involves the intramolecular cyclization of the in situ generated ketimine moiety via the formation of dihydrospiroindolequinoline, which serves as a key intermediate in the reaction pathway. Several control experiments and spectroscopic studies were performed to elucidate the underlying reaction mechanism.",10.1021/acs.orglett.4c01091,2024-05-01,0.5852789620143477
Organic Letters,"Diastereoselective Formal Total Synthesis of the DNA Polymerase α Inhibitor, Aphidicolin, Using Palladium-Catalyzed Cycloalkenylation and Intramolecular Diels−Alder Reactions",[structure: see text] A novel diastereoselective formal synthesis of aphidicolin has been achieved by exploiting a unique characteristic of a bicyclo[3.2.1]octane prepared by employing a palladium-catalyzed cycloalkenylation process.,10.1021/ol034027+,2003-03-27,0.5852783365472041
Tetrahedron,Efficient and stereoselective installation of isoquinoline: formal total synthesis of cortistatin A,,10.1016/j.tetlet.2009.02.038,2009-02-11,0.5852766382027281
Journal of Organic Chemistry,Stereocontrolled Synthesis of Ara-Type Cyclohexenyl Nucleosides,"A highly stereocontrolled synthesis of a new class of carbocyclic nucleosides, ara-type cyclohexenyl nucleosides, was developed. The key intermediate (+/-)-9 was obtained after a series of transformations starting from easily available endo-bicyclo carboxylic acid (+/-)-3. The allylic hydroxyl group of (+/-)-9 was masked via oxidation with manganese dioxide and released, after protection of the 2'-hydroxyl group, via reduction with NaBH(4) in the presence of CeCl(3).7H(2)O. The base moiety was introduced with use of the Mitsunobu methodology.",10.1021/jo0300946,2003-05-01,0.5852725249380983
Tetrahedron,Total synthesis of (±)-allosamizoline from a symmetric trisubstituted cyclopentene,"A convergent synthesis of the aminocyclitol allosamizoline 1, which is found in a class of pseudotrisaccharide chitinase inhibitors known as the allosamidins, is reported.",10.1016/0040-4039(94)88208-8,1994-09-01,0.5852720681355671
Angewandte Chemie International Edition,"Practical Synthesis of Chiral Allylboronates by Asymmetric 1,1‐Difunctionalization of Terminal Alkenes","We report herein a modular catalytic method for the efficient enantioselective synthesis of chiral allylboronates from abundant feedstock chemicals through an asymmetric 1,1-difunctionalization of alkenes. This protocol is distinguished by its use of an inexpensive chiral catalyst, mild and convenient reaction conditions, wide substrate scope, scalability and practicality. The utility of this method is demonstrated by the rapid synthesis of key intermediates of complex drug molecules. Mechanistic studies reveal that β-H elimination is a highly regioselective step and the reversible homolysis and convergance to the lower energy pre-reductive elimination intermediate is the enantio-determining step.",10.1002/anie.202209076,2022-07-21,0.5852677411637606
Journal of the American Chemical Society,Total Synthesis of the Salicylate Enamide Macrolide Oximidine II,The asymmetric synthesis of the salicylate enamide macrolide oximidine II is reported. The synthesis involves a highly regio- and stereoselective ring-closing metathesis of a bis-diene substrate to construct the macrocyclic triene core. Copper(I)-mediated amidation of a (Z)-vinyl iodide was employed to attach the enamide side chain.,10.1021/ja034030o,2003-04-29,0.5852659295004354
Tetrahedron,Studies on the asymmetric total synthesis of trichothecenes. Stereoselective construction of the c-ring fragment,,10.1016/s0040-4039(00)89245-x,1985-01-01,0.5852556134961375
Tetrahedron,Coupling of isoprenoid triflates with organoboron nucleophiles: Synthesis of all-trans-geranylgeraniol,,10.1016/0040-4039(95)01119-3,1995-08-01,0.5852534803211507
Tetrahedron,Coupling of Isoprenoid Triflates with Organoboron Nucleophiles: Synthesis of all-trans-Geranylgeraniol,,10.1016/00404-0399(50)11193-,1995-08-07,0.5852534803211507
Synlett,Expedient Route to an Amine Precursor of Halichlorine and Pinnaic Acid from Nitrocyclopent-1-ene,"Diastereoselective addition of n-propanal to nitrocyclopent-1-ene, aldehyde protection, 1,6-conjugate addition, and cross metathesis provides a facile route to key amine precursors of halichlorine and pinnaic acid.",10.1055/s-0029-1219337,2010-01-19,0.5852518620355266
Organic Process Research & Development,A Short Route to Midazolam via Michael Addition to a Nitroolefin,"High Resolution Image Download MS PowerPoint Slide A new approach to midazolam through Michael addition of 2-aminobenzophenone with a nitroolefin as a key step is reported. We devised a telescoped four-step synthesis using only one single protecting group, resulting in an excellent atom economy.",10.1021/acs.oprd.5c00320,2025-10-14,0.5852503975424327
Journal of Organic Chemistry,Stereoselective Total Synthesis of the Pseudopterolide Kallolide A,"A total synthesis of the pseudopterolides, kallolide A (36) and kallolide A acetate (35), has been achieved. The racemic forms were prepared from the syn adduct 20 of furan 13 and stannane 17 (BF(3).OEt(2)-promoted addition) via the 15-membered propargylic allylic ether 25. [2,3]Wittig ring contraction led to the cis, anti, cis product 26. Alcohol 26 was transformed to butenolide 34 with net retention of configuration by Pd(PPh(3))(4)-catalyzed carbonylation of the mesylate 27 and ensuing AgNO(3)-catalyzed cyclization of the derived allenic acid 29. Solvolysis of the SEM ether (at C2) 34 in acetic acid or aqueous t-BuOH afforded racemic kallolide A acetate (35) and kallolide A (36), respectively, with inversion of stereochemistry by an S(N)1 process. Key elements of stereocontrol, including the steric outcome of the [2,3]Wittig ring contraction, the allenic ester isomerization, and the solvolysis reactions, were predicted from molecular mechanics calculations. The C8 and C2 epimers 45 and 46 of the cis, anti, cis kallolide A SEM ether precursor 34 were also prepared. The synthetic route originated from the anti adduct 19 of aldehyde 13 and the allylic chloride 16 and CuCl (cat), HSiCl(3), and i-Pr(2)NEt. Adduct 19 was subjected to the same sequence as the syn counterpart 20 to produce the trans, anti, cis [2,3]Wittig ring contraction product 42. The derived allenoate 44 afforded a 1:1 mixture of butenolides 45 and 46 upon sequential treatment with TBAF and AgNO(3). Finally, the natural enantiomer (+)-36 of kallolide A was synthesized from the enantioenriched syn adduct (+)-20, prepared by addition of allylic stannane 17 to aldehyde 13 promoted by a modified chiral acyloxyborane Lewis acid.",10.1021/jo980603h,1998-08-01,0.5852495607669531
Tetrahedron,Enantioselective total synthesis of enokipodins A–D,,10.1016/j.tetlet.2004.04.191,2004-05-30,0.5852471401748781
Tetrahedron,Enantioselective total synthesis of cineromycin B,,10.1016/j.tetlet.2003.10.021,2003-11-24,0.5852471401748781
Tetrahedron,An enantioselective total synthesis of the macrolide Patulolide C,,10.1016/s0040-4039(01)93736-0,1989-01-01,0.5852471401748781
Tetrahedron,First enantioselective total synthesis of (−)-heliannuol C,,10.1016/j.tetlet.2003.09.086,2003-10-16,0.5852471401748781
Tetrahedron,An enantioselective total synthesis of (+)-picrasin B,,10.1016/s0040-4039(01)93835-3,1989-01-01,0.5852471401748781
Tetrahedron,An enantioselective total synthesis of the macrodiolide (−)-(RRR)-colletallol,,10.1016/0040-4039(91)80367-f,1991-03-01,0.5852471401748781
Tetrahedron,Enantioselective total synthesis of sacrolide A,,10.1016/j.tetlet.2017.09.017,2017-09-09,0.5852471401748781
Tetrahedron,Enantioselective total synthesis of (−)-D-noviose,,10.1016/s0040-4039(98)00295-0,1998-04-01,0.5852471401748781
Tetrahedron,Enantioselective total synthesis of medermycin (lactoquinomycin),,10.1016/s0040-4039(00)97881-x,1990-01-01,0.5852471401748781
Tetrahedron,"Enantioselective total synthesis of bilobalide, A C15 ginkgolide",,10.1016/0040-4039(88)85179-7,1988-01-01,0.5852471401748781
Tetrahedron,Enantioselective Total Synthesis of Didesepoxyrhizoxin,,10.1016/00404-0399(50)09264-,1995-07-03,0.5852471401748781
Tetrahedron,Enantioselective total synthesis of (+)-monomorine I,,10.1016/s0040-4039(00)82186-3,1988-01-01,0.5852471401748781
Tetrahedron,"Enantioselective total synthesis of polyoxygenated cyclohexanoids: (+)-streptol, ent-RKTS-33 and putative ‘(+)-parasitenone’. Identity of parasitenone with (+)-epoxydon",,10.1016/j.tetlet.2005.03.087,2005-04-11,0.5852471401748781
Tetrahedron,Enantioselective total synthesis of (+)-(S)-dihydroperiphylline,,10.1016/s0040-4039(01)80739-5,1989-01-01,0.5852471401748781
Tetrahedron,Enantioselective total synthesis of (+)-negamycin,,10.1016/s0040-4039(00)86063-3,1988-01-01,0.5852471401748781
Tetrahedron,The first enantioselective total synthesis of (−)-arisugacin A,,10.1016/s0040-4039(02)02094-4,2002-11-01,0.5852471401748781
Tetrahedron,Enantioselective total synthesis of (S)-(−)-quinolactacin B,,10.1016/j.tetlet.2008.04.130,2008-04-28,0.5852471401748781
Tetrahedron,Enantioselective total synthesis of enokipodins A?D,,10.1016/s0040-4039(04)01032-9,2004-05-01,0.5852471401748781
Tetrahedron,Enantioselective total synthesis of (+)-digitoxigenin,,10.1016/j.tetlet.2007.01.024,2007-01-08,0.5852471401748781
Tetrahedron,An enantioselective total synthesis of (+)-cassiol,,10.1016/s0040-4039(96)02191-0,1996-12-01,0.5852471401748781
Angewandte Chemie International Edition,Enantioselective Total Synthesis of the Nonisoprenoid Sesquiterpene (−)-Kumausallene,,10.1002/(sici)1521-3773(19991102)38:21<3175::aid-anie3175>3.3.co;2-d,1999-11-02,0.5852471401748781
Tetrahedron,Enantioselective total synthesis of salicylihalamides A and B,,10.1016/s0040-4039(01)00278-7,2001-04-01,0.5852471401748781
Tetrahedron,Enantioselective total synthesis of all four stereoisomers of Yingzhaosu C,,10.1016/s0040-4039(00)78561-3,1994-12-01,0.5852471401748781
Tetrahedron,Enantioselective total synthesis of (−)-preclavulone-A,,10.1016/0040-4039(88)85317-6,1988-01-01,0.5852471401748781
Tetrahedron,Stereo- and enantioselective total synthesis of sarcophytol-A,,10.1016/s0040-4039(00)89053-x,1990-01-01,0.5852471401748781
Tetrahedron,"Enantioselective total synthesis of (+)-tetrahydroalstonine, (+)-acricine, and (+)-reserpinine",,10.1016/s0040-4039(00)94677-x,1990-01-01,0.5852471401748781
Tetrahedron,Enantioselective total synthesis of heliespirone B,,10.1016/j.tetlet.2011.12.115,2012-01-10,0.5852471401748781
Tetrahedron,An enantioselective total synthesis of phomopsolide C,,10.1016/s0040-4039(02)01866-x,2002-11-01,0.5852471401748781
Tetrahedron,"First enantioselective total synthesis of penicimarin B, aspergillumarins A and B",,10.1016/j.tetlet.2014.03.067,2014-03-22,0.5852471401748781
Tetrahedron,Corrigendum to “Enantioselective total synthesis of (+)-digitoxigenin”,,10.1016/j.tetlet.2007.01.109,2007-01-26,0.5852471401748781
Tetrahedron,Enantioselective total synthesis of (−)-ericanone,,10.1016/j.tetlet.2012.12.033,2012-12-20,0.5852471401748781
Angewandte Chemie International Edition,Application of a Palladium‐Catalyzed C−H Functionalization/Indolization Method to Syntheses of <i>cis</i>‐Trikentrin A and Herbindole B,We describe herein formal syntheses of the indole alkaloids cis-trikentrin A and herbindole B from a common meso-hydroquinone intermediate prepared by a ruthenium-catalyzed [2+2+1+1] cycloaddition that has not been used previously in natural product synthesis. Key steps include a sterically demanding Buchwald-Hartwig amination as well as a unique C(sp(3) )-H amination/indole formation. Studies toward a selective desymmetrization of the meso-hydroquinone are also reported.,10.1002/anie.201605475,2016-08-29,0.5852468038503538
Angewandte Chemie International Edition,Selective Inhibition of Glycosidases by Feedback Prodrugs,"In the loop: A novel concept for the selective inhibition of glycosidases has been developed whereby a glycosidase inhibitor is released by glycosidase-mediated hydrolysis of a prodrug, which subsequently inhibits the glycosidase that initiated the release of the inhibitor.",10.1002/anie.200600808,2006-07-17,0.5852404869193767
Synthesis,Asymmetric Total Syntheses of the trans-2-Aryl-6-alkyltetrahydropyrans Diospongin B and Parvistones D and E from a Common Precursor,"Asymmetric total syntheses of diospongin B and parvistones D and E are reported. Our strategy features a high-yielding three-step reaction sequence: Achmatowicz rearrangement, reductive γ-deoxygenation, and Matsuda–Heck coupling to construct the rare and challenging trans -2-aryl-6-alkyltetrahydropyrans, which serve as common intermediates for the syntheses of diospongin B, and parvistones D and E.",10.1055/s-0035-1561592,2016-04-12,0.5852398063332738
European Journal of Organic Chemistry,Stereoselective Synthesis of <i>gem</i>‐Difluoromethylenated Linear Azatriquinanes,"The stereoselective synthesis of gem ‐difluoromethylenated linear azatriquinanes is described herein. The fluoride‐catalyzed nucleophilic addition of PhSCF 2 SiMe 3 ( 1 ), exploited as a gem ‐difluoromethylene (‐CF 2 ‐) building block, to chiral phthalimide 2 provided the corresponding gem ‐difluoromethylenated adduct 3 in high yield as a diastereomeric mixture. The stereoselective intramolecular radical cyclization of 3 furnished chiral linear azatriquinanes 4 , the hydroxy group of which subsequently underwent nucleophilic substitution by organosilanes to provide 5 with high stereoselectivity. Treatment of 5 with Grignard reagents or a reducing agent provided a collection of chiral gem ‐difluoromethylenated linear azatriquinanes 6 – 8 .",10.1002/ejoc.201701415,2017-11-14,0.585238609402391
Chemical Science,"Ligand-dependent, palladium-catalyzed stereodivergent synthesis of chiral tetrahydroquinolines","YuePhos, which can be easily derived from inexpensive and commercially available starting materials in four chemical operations. Through switching of three chiral ligands, an unprecedented ligand-dependent diastereodivergent Pd-catalyzed asymmetric intermolecular [4 + 2] cycloaddition reaction of vinyl benzoxazinanone with α-arylidene succinimides was developed. This novel method provides an efficient route for the stereodivergent synthesis of six stereoisomers of pyrrolidines bearing up to three adjacent stereocenters (one quaternary center). Despite the anticipated challenges associated with controlling stereoselectivity in such a complex system, the products are obtained in enantiomeric excesses ranging up to 98% ee. In addition, the synthetic utilities of optically active hexahydrocarbazoles are also shown.",10.1039/d2sc02771b,2022-01-01,0.5852352577376831
Synlett,"Transition Metals in OrganicSynthesis, Part 87: AnEfficient Palladium-Catalyzed Route to 2-Oxygenated and2,7-Dioxygenated Carbazole Alkaloids - Total Synthesisof 2-Methoxy-3-methylcarbazole, Glycosinine, Clausine L, Mukonidine,and Clausine V","Optimization of the palladium(II)-catalyzed oxidative cyclization of N,N-diarylamines opens up the way to an efficient synthesis of 2-oxygenated and 2,7-dioxygenated carbazole alkaloids including 2-methoxy-3-methylcarbazole, glycosinine, clausine L, mukonidine, and clausine V.",10.1055/s-2008-1078508,2008-07-02,0.5852335452678448
Organic Process Research & Development,A Scalable One-Pot Process for the Synthesis of Florfenicol Phosphodiester,"A practical and scalable one-pot process for the preparation of florfenicol phosphodiester ( 3 ), a new water-soluble prodrug of florfenicol ( 1 ), has been developed by adopting the phosphorylating system of POCl 3 /pyridine/CH 3 CN. The yield of 3 was 80.72%, and its HPLC purity reached as high as 99.20%, while the content of the maximum impurity was reduced to 0.28% under the optimum conditions. The present process has proven to be reliable on 500-g and 4-kg scale in the pilot plant.",10.1021/op500038s,2014-03-20,0.58522950755758
Tetrahedron,Synthesis of an HMG-COA reductase inhibitor; A diastereoselective aldol approach,,10.1016/s0040-4039(01)83844-2,1987-01-01,0.5852273195799873
Tetrahedron,Synthesis of an HMG-CoA reductase inhibitor; a diastereoselective aldol approach,,10.1016/s0040-4039(00)95933-1,1987-01-01,0.5852273195799873
Journal of the American Chemical Society,A Sequential Strand-Displacement Strategy Enables Efficient Six-Step DNA-Templated Synthesis,We developed a sequential strand-displacement strategy for multistep DNA-templated synthesis (DTS) and used it to mediate an efficient six-step DTS that proceeded in 35% overall yield (83% average yield per step). The efficiency of this approach and the fact that the final product remains linked to a DNA sequence that fully encodes its reaction history suggests its utility for the translation of DNA sequences into high-complexity synthetic libraries suitable for in vitro selection.,10.1021/ja201361t,2011-06-09,0.5852166682017097
Organic Process Research & Development,Development and Optimization of a Scalable Enzymatic Cascade-Carbamate Formation Telescope Process for the Synthesis of CDK2 Selective Candidate Tegtociclib (PF-07104091),"PF-07104091 (tegtociclib) is a cyclin-dependent kinase 2 (CDK2) selective inhibitor under investigation as an oncology treatment with breast cancer as the leading indication. In this report, we detail the development and optimization of a selective enzyme cascade-carbamate formation telescoped sequence for the synthesis of PF-07104091. The newly developed process enables exquisite stereochemical control and efficient processing, affording crude active pharmaceutical ingredient (API) in good yield and high purity while demonstrating reduced process mass intensity (PMI) and cycle time. This optimized highly efficient and sustainable process was demonstrated during pilot plant scale production of >450 kg of PF-07104091.",10.1021/acs.oprd.5c00268,2025-10-07,0.5852119171590198
Organic Process Research & Development,A New Industrial Process for Oxcarbazepine,"A novel industrial process for the antiepileptic drug oxcarbazepine 1 has been developed. Unlike the old process, the new process is free from halogenated solvents and can be performed in standard production equipment. It starts from commercially available 1,3-dihydro-1-phenyl-2H-indol-2-one 10 . In the key step, an electrophilic ring closure reaction of 2-[(methoxycarbonyl)phenylamino] benzeneacetic acid 5 to 10,11-dihydro-10-oxo-5H-dibenz[ b, f ]azepine-5-carboxylic acid methyl ester 6 in poly phosphoric acid was applied. For the manufacture of 5, a highly efficient process using a dianion strategy was developed.",10.1021/op049760a,2005-04-05,0.5852081944831738
Journal of Organic Chemistry,"Cyclobutene Ring-Opening of Bicyclo[4.2.0]octa-1,6-dienes: Access to CF<sub>3</sub>-Substituted 5,6,7,8-Tetrahydro-1,7-naphthyridines","An efficient method for the synthesis of novel CF(3)-substituted tetrahydro-1,7-naphthyridines including cyclic α-amino acid derivatives has been developed. The method is based on unusual cyclobutene ring-opening of bicyclo[4.2.0]octa-1,6-dienes with pyrrolidine to afford the corresponding 1,5-diketones followed by their heterocyclization. A convenient one-pot procedure has been also elaborated starting from readily available trifluoromethylated 1,6-allenynes.",10.1021/jo301501r,2012-09-05,0.585203865242616
Organic Process Research & Development,"Frakefamide, an Analgesic Tetrapeptide:  Development of a Pilot-Plant-Scale Process","A pilot-plant-process is described where frakefamide × HCl ( l -tyrosyl- d -alanyl- p -fluoro- l -phenylalanyl- l -phenylalaninamide hydrochloride) was synthesised from its amino acid monomers in seven steps. The synthesis was performed in 70-L equipment, and the final product was obtained in 70% overall yield and in 99.5% purity. Only two intermediates were isolated, and the process required no chromatography. Peptide bond formation was promoted by isobutyl chloroformate-mediated mixed anhydride coupling reactions. The formed mixed anhydrides proved to be surprisingly stable, in most cases for several hours at −10 °C, and therefore suitable for large-scale peptide synthesis. Only traces, if any, of racemised coupling products were obtained. Benzyloxycarbonyl was used as amino protecting group throughout the synthesis, and its removal by hydrogenolysis proved to be fast and convenient on a large scale.",10.1021/op020060k,2002-10-23,0.5851987883130337
Tetrahedron,"A novel indene synthesis from N-phenyl-1, 1-diphenyl-2-ethylbut-3-ynylamine",,10.1016/s0040-4039(00)85900-6,1982-01-01,0.5851860498665505
Organic Process Research & Development,An Improved Procedure for Preparation and Isolation of Cephalosporin Antibiotic: Cefozopran as Free Base,"An efficient synthesis of cephalosporin antibiotic, cefozopran is described. The present process does not involve chromatographic purification for isolation and is cost-effective and amenable to large-scale synthesis.",10.1021/op900128z,2009-07-07,0.5851740934520726
Synlett,Stereoselective Cycloaddition on Carbohydrates for the Synthesis of New Bicyclic Oxazolidines Bearing a Quaternary Bridgehead,"A new carbohydrate nitrone intramolecular cycloaddition reaction is described for the enantioselective synthesis of bicyclic oxazolidines. By choice of the precursor, the products possess a chiral quaternary bridgehead aryl substitution. Also described is the diverse synthesis of 6-keto and 6-alkenyl carbohydrates by a general approach. The overall protocol provides versatility through the possibility of introducing diverse reagents at several entry points.",10.1055/s-2005-869836,2005-01-01,0.5851734121478273
Synthesis,"Preparation of (2,2-Dimethylhexahydrofuro[2,3-<i>c</i>]pyrrol-6-yl)methanol: A Conformationally Restricted Congener of Nonproteinogenic 3-Hydroxy-4-methylproline",Lactam 6 derived from (S)-pyroglutaminol was converted to a conformationally restricted congener of nonproteinogenic 3-hydroxy-4-methylproline. Preparation of precursor 5b was achieved via a diastereoselective epoxidation followed by a regioselective opening of the oxirane ring. Iodine-mediated cyclization was used to assemble the ether moiety of 2.,10.1055/s-2003-42426,2003-01-01,0.5851716946256822
European Journal of Organic Chemistry,Stereoselective Synthesis of the C(1)−C(12) Fragments of Tedanolides − Application of a syn-Selective Tin(II)-Mediated Aldol Reaction and a Convertible Methoxybenzyl Protecting Group,"Stereoselective synthesis of two C(1)−C(12) fragments, 3 and 4, of antitumor agents tedanolide (1) and 13-deoxytedanolide (2) was achieved by means of several regio- and/or stereoselective reactions. Ethyl ketone 14 was synthesized from methyl (S)-3-hydroxy-2-methylpropionate (16a) by way of a Weinreb amide. A highly syn-selective tin(II)-mediated aldol reaction between 14 and aldehyde 15, prepared from (R)-propionate 16b, proceeded smoothly, and subsequent reduction gave diol 13, which was transformed into 3, incorporating a C(3),C(5)-MP acetal moiety, by taking advantage of convertible MPM protecting groups. Another fragment, 4, with C(3)-O-methyl and C(5)-O-MPM groups, was also synthesized. A crucial step was the selective transformation of C(2),C(3)-diol 21 into C(2)-O-TBS, C(3)-O-Me compound 22.",10.1002/1099-0690(200110)2001:19<3615::aid-ejoc3615>3.0.co;2-p,2001-10-01,0.5851677413736626
Tetrahedron,"(±) 4β-amino-2α,3α-dihydroxy-1β-cyclopentanemethanol hydrochloride. Carbocyclic ribofuranosylamine for the synthesis of carbocyclic nucleosides.",,10.1016/s0040-4039(01)82898-7,1981-01-01,0.5851676871404751
Synthesis,"The Synthesis of Pyrazolo[1,5-<i>b</i>][1,2,4]triazines, A New Heterocyclic Ring System","All articles of this category Four representatives of the new ring system pyrazolo[1,5- b ][1,2,4]triazine were prepared by N -amination of 3(5)-aminopyrazole or its 5(3)-phenyl derivative and cyclocondensation of the resultant 1,5-diaminopyrazoles with glyoxal, butanedione, or benzil.",10.1055/s-1986-31483,1986-01-01,0.5851631962733942
Journal of Organic Chemistry,"Synthesis of Higher Oxidized Metabolites of Dibenz[<i>a</i>,<i>j</i>]anthracene Implicated in the Mechanism of Carcinogenesis","Higher oxidized metabolites are implicated as active carcinogenic forms of polycyclic aromatic hydrocarbons which have two or more bay or fjord molecular regions, such as dibenz[ a, j ]anthracene. These include the bis(dihydrodiols) and phenolic dihydrodiols which may potentially undergo further metabolism to the corresponding diol epoxides. The latter react with DNA resulting in mutations that lead to tumorigenesis. Prior characterization of these metabolites has been based largely on HPLC and spectroscopic evidence. This paper reports efficient syntheses of the trans-trans- 3,4,8,9-dihydrodiol ( 1 ) and the 10- and 11-phenolic trans -3,4-dihydrodiols of dibenz[ a, j ]anthracene ( 3a, b ). The synthetic route to 1 entails as the key steps asymmetric dihydroxylation of an appropriately substituted stilbene precursor employing a Sharpless catalyst followed by intramolecular cyclodehydrobromination catalyzed by Pd(PPh 3 ) 2 Cl 2 . The syntheses of 3a, b proceed via sequences involving a Wittig reaction of anisaldehyde with a phosphonium salt of 2-chloro-3-methylbenzyl bromide to give a stilbene compound and then photocyclization, conversion of the product to a phosphonium salt, a second Wittig reaction and photocyclization, reductive dechlorination, and conversion of the resulting trimethoxydibenz[ a, j ]anthracenes to the phenolic dihydrodiols. A key feature of these syntheses is the effective use of chloro substituents to block photocyclization in an undesired direction. These methods are potentially applicable to the synthesis of analogous higher oxidized metabolites of other polycyclic aromatic carcinogens.",10.1021/jo980416j,1998-10-22,0.5851631260009542
Organic Letters,Iodination of Remote <i>Ortho</i>-C–H Bonds of Arenes via Directed S<sub>E</sub>Ar: A Streamlined Synthesis of Tetrahydroquinolines,"A new strategy for the synthesis of tetrahydroquinolines (THQs) via the sequential functionalizations of remote C-H bonds is reported. This method uses a single picolinamide directing/protecting group to effect Pd-catalyzed γ-C(sp(3))-H arylation, metal-free ε-C(sp(2))-H iodination, and Cu-catalyzed intramolecular C-N cross-coupling. The overall sequence is efficient and versatile, and offers a streamlined synthesis of THQs with complex substitution patterns from readily available aryl iodide and aliphatic amine precursors.",10.1021/ol4015078,2013-06-20,0.5851607965989067
Angewandte Chemie International Edition,A Modular Approach to the Antifungal Sphingofungin Family: Concise Total Synthesis of Sphingofungin A and C,"Sphingofungins are fungal natural products known to inhibit the biosynthesis of sphingolipids which play pivotal roles in various cell functions. Here, we report a short and flexible synthetic approach towards the sphingofungin family. Key step of the synthesis was a decarboxylative cross-coupling reaction of chiral sulfinyl imines with a functionalized tartaric acid derivative, which yielded the core motif of sphingofungins carrying four consecutive stereocenters and a terminal double bond. Subsequent metathesis reaction allowed for the introduction of different side chains of choice resulting in a total of eight sphingofungins, including for the first time sphingofungin C (eight steps from commercially available protected tartaric acid with an overall yield of 6 %) and sphingofungin A (ten steps). All newly synthesized derivatives were tested for their antifungal, cell-proliferative and antiparasitic activity unraveling their structure-activity relations.",10.1002/anie.202112616,2021-10-22,0.5851578765474679
Tetrahedron,Synthetic directions towards capsular polysaccharide of Streptococcus pneumoniae serotype 18C,,10.1016/j.tetlet.2019.151153,2019-09-13,0.5851563388727524
Tetrahedron,Synthetic entry into cyclopentyl analogs of muscarine,,10.1016/s0040-4039(01)91864-7,1974-01-01,0.5851563388727524
Tetrahedron,Synthetic proanthocyanidin,,10.1016/s0040-4039(00)62004-x,1966-01-01,0.5851563388727524
Tetrahedron,"A synthetic, electrically neutral carrier for Ca",,10.1016/s0040-4039(01)84850-4,1972-01-01,0.5851563388727524
Tetrahedron,Synthetic periplogenin,,10.1016/s0040-4039(01)90967-0,1963-01-01,0.5851563388727524
Tetrahedron,A totally synthetic entry into the veratrum alkaloid skeleton,,10.1016/s0040-4039(00)90236-3,1965-01-01,0.5851563388727524
Tetrahedron,Torsional entropy as co-operator: A device for synthetic allostery,,10.1016/s0040-4039(00)80669-3,1988-01-01,0.5851563388727524
Tetrahedron,Synthetic incorporation of cincholoipon into ipecacuanha alkaloids,,10.1016/s0040-4039(00)71969-1,1975-01-01,0.5851563388727524
Tetrahedron,Synthetic diversification of tryptanthrin through its C6-hydrazone,,10.1016/j.tetlet.2023.154752,2023-09-09,0.5851563388727524
Tetrahedron,"A synthetic entry into tetracyclo (4.2.0.02,4.03,8) octane system",,10.1016/0040-4039(80)80189-4,1980-01-01,0.5851563388727524
Synlett,Convergent Synthesis of 4-Thiomaltooligosaccharides,"Methyl 4,4II,4III-trithio-α-maltotetraoside (2) and its pentasaccharide homologue 3 were conveniently synthesized by treatment of methyl 4II-O-triflyl-4-thiomaltoside derivative 10 with the respective peracetylated 1,4-dithio- and 1,4,4II-trithio-maltooligosaccharides 16 and 18, in the presence of diethylamine",10.1055/s-2003-40334,2003-06-30,0.5851547208222803
Organic Letters,Multicomponent Linchpin Couplings of Silyl Dithianes:  Synthesis of the Schreiber C(16−28) Trisacetonide Subtarget for Mycoticins A and B,"[formula: see text] An efficient synthesis of trisacetonide (+)-11, the Schreiber C(16-28) subtarget for mycoticins A and B, is described. The key synthetic transformation entails a one-flask, five-component linchpin coupling tactic.",10.1021/ol991166b,1999-11-09,0.5851507978474473
Synlett,Construction of 8-Membered Ring Skeleton of Vinigrol <i>via</i> SmI<sub>2</sub>-Promoted Barbier Coupling,"All articles of this category The 8-membered ring framework of vinigrol, a unique tricyclic diterpene isolated as a novel antihypertensive compound from a culture of Virgaria nigra , was efficiently synthesized employing an SmI 2 -induced intramolecular Barbier coupling. vinigrol - diterpene - samarium(II) iodide - Barbier coupling",10.1055/s-1997-748,1997-02-01,0.5851489404196211
European Journal of Organic Chemistry,Synthesis of (+)‐Centrolobine and Its Analogues by Using Acyl Anion Chemistry,"Abstract A new route based on the use of acyl anion chemistry was developed for the synthesis of (+)‐centrolobine and its analogues. Acid‐catalyzed benzylic cation initiated cyclization was the key step in the stereoselective formation of the cis ‐2,6‐disubstituted tetrahydropyran ring. The developed methodology was applied to the synthesis of (+)‐centrolobine analogues containing electron‐donating substituents in the aryl rings.",10.1002/ejoc.201300097,2013-03-05,0.5851452855209409
Tetrahedron,Enantioselective total synthesis of the pumiliotoxin a alkaloids via reductive iminium ion-alkyne cyclizations. Total synthesis of (+)-pumiliotoxin a,,10.1016/s0040-4039(00)82477-6,1988-01-01,0.5851380276245355
Tetrahedron,"Stereospecific route to enantiopure all cis-2,3,6-trisubstituted piperidines. Facile synthesis of (−)-deoxocassine and (+)-azimic acid",,10.1016/s0040-4039(03)00820-7,2003-05-01,0.5851349175190553
Tetrahedron,A total synthesis of (+)-brefeldin a,,10.1016/s0040-4039(00)71000-8,1979-01-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-filifolone.,,10.1016/s0040-4039(00)71447-x,1980-01-01,0.585130102153097
Tetrahedron,Total synthesis of (−) homothienamycin,,10.1016/s0040-4039(00)71368-2,1980-01-01,0.585130102153097
Tetrahedron,"Total synthesis of a cyclophane alkaloid, (+/-)-lythranidine",,10.1016/s0040-4039(01)85971-2,1979-01-01,0.585130102153097
Tetrahedron,Total synthesis of (±) Xyloketal H,,10.1016/j.tetlet.2015.03.118,2015-04-05,0.585130102153097
Tetrahedron,Total synthesis of (±)-γ-indomycinone,,10.1016/j.tetlet.2015.03.010,2015-03-09,0.585130102153097
Tetrahedron,"First total synthesis of (6S,1′S,2′S)-hydroxypestalotin",,10.1016/j.tetlet.2015.06.009,2015-06-12,0.585130102153097
Tetrahedron,Total synthesis of α- and β-panasinsene,,10.1016/0040-4039(80)80104-3,1980-01-01,0.585130102153097
Tetrahedron,Corrigendum to “Total synthesis of hirsutellide A”,,10.1016/j.tetlet.2006.11.038,2006-12-13,0.585130102153097
Tetrahedron,Total synthesis of dysiherbaine,,10.1016/j.tetlet.2007.05.180,2007-06-11,0.585130102153097
Tetrahedron,Total synthesis of 1-(Z)-atractylodinol,,10.1016/j.tetlet.2006.08.130,2006-09-29,0.585130102153097
Tetrahedron,Total synthesis of mallotophilippen C,,10.1016/j.tetlet.2006.04.064,2006-05-11,0.585130102153097
Tetrahedron,Total synthesis of dapiramicin B,,10.1016/j.tetlet.2006.06.001,2006-06-20,0.585130102153097
Tetrahedron,Total synthesis of aplysinoplide B,,10.1016/j.tetlet.2015.04.010,2015-04-10,0.585130102153097
Tetrahedron,Total synthesis of (−)-axamide-4 and (−)-axisonitrile-4,,10.1016/0040-4039(95)00542-k,1995-05-01,0.585130102153097
Angewandte Chemie International Edition,Total Synthesis of (±)-Gelsemine,,10.1002/(sici)1521-3773(19991004)38:19<2934::aid-anie2934>3.3.co;2-c,1999-10-04,0.585130102153097
Tetrahedron,Total synthesis of (±) zoapatanol,,10.1016/s0040-4039(01)81819-0,1981-01-01,0.585130102153097
Tetrahedron,Total synthesis of (+)-petromyroxol,,10.1016/j.tetlet.2015.04.129,2015-05-05,0.585130102153097
Tetrahedron,First total synthesis of antimalarial (+)-cryptorigidifoliol A,,10.1016/j.tetlet.2015.08.029,2015-08-14,0.585130102153097
Tetrahedron,The total synthesis of renierone,,10.1016/0040-4039(80)80148-1,1980-01-01,0.585130102153097
Tetrahedron,"Total synthesis of a macrocyclic spermidine alkaloid, codonocarpine",,10.1016/s0040-4039(00)71158-0,1980-01-01,0.585130102153097
Tetrahedron,"Total synthesis of kukoamine A, an antihypertensive constituent of",,10.1016/0040-4039(81)80030-5,1981-01-01,0.585130102153097
Tetrahedron,Total synthesis of heliespirone B,,10.1016/j.tetlet.2015.06.093,2015-07-04,0.585130102153097
Tetrahedron,Total synthesis of Pallavicinia diterpenoids: An overview,,10.1016/j.tetlet.2016.11.025,2016-11-11,0.585130102153097
Tetrahedron,A total synthesis of the alkaloid deplancheine,,10.1016/s0040-4039(00)92601-7,1980-01-01,0.585130102153097
Tetrahedron,A total synthesis of d1-coriolin,,10.1016/0040-4039(80)80242-5,1980-01-01,0.585130102153097
Synlett,The Total Synthesis of (±)-lsonitrin B (Deoxytrichoviridin),,10.1055/s-1989-20334,1989-01-01,0.585130102153097
Tetrahedron,"Total synthesis of heliannuol B, an allelochemical from Helianthus annuus",,10.1016/j.tetlet.2007.07.177,2007-08-01,0.585130102153097
Tetrahedron,Total synthesis of (−)-centrolobine,,10.1016/j.tetlet.2008.08.102,2008-09-01,0.585130102153097
Tetrahedron,A total synthesis of -cerulenin and -tetrahydrocerulenin,,10.1016/s0040-4039(01)83776-x,1977-01-01,0.585130102153097
Tetrahedron,A total synthesis of the kessanols,,10.1016/s0040-4039(01)83353-0,1977-01-01,0.585130102153097
Tetrahedron,Total synthesis of dl-pederamide,,10.1016/s0040-4039(00)93015-6,1976-12-01,0.585130102153097
Tetrahedron,Total synthesis of rac-longamide B,,10.1016/j.tetlet.2007.03.022,2007-03-13,0.585130102153097
Tetrahedron,Total synthesis and stereochemical reassignment of maedamide,,10.1016/j.tetlet.2015.06.090,2015-07-04,0.585130102153097
Tetrahedron,Total synthesis of carbomycin B and josamycin (leucomycin A3),,10.1016/s0040-4039(00)78621-7,1980-01-01,0.585130102153097
Tetrahedron,A total synthesis of chelidonine,,10.1016/0040-4039(80)80196-1,1980-01-01,0.585130102153097
Tetrahedron,Total synthesis of -mexicanin I and -linifolin A,,10.1016/s0040-4039(01)95380-8,1979-01-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-Lycodine,,10.1016/s0040-4039(01)86523-0,1979-01-01,0.585130102153097
Tetrahedron,The total synthesis of (−)-mesembranone,,10.1016/s0040-4039(01)86629-6,1979-01-01,0.585130102153097
Tetrahedron,The total synthesis of -dihydrocallitrisin,,10.1016/s0040-4039(01)95373-0,1979-01-01,0.585130102153097
Tetrahedron,"Total Synthesis of 2,4-methanaproline",,10.1016/0040-4039(80)80077-3,1980-01-01,0.585130102153097
Tetrahedron,A total synthesis of (±)cerulenin,,10.1016/s0040-4039(01)83370-0,1977-01-01,0.585130102153097
Tetrahedron,Total synthesis of d1 pedaldehyde,,10.1016/s0040-4039(01)85432-0,1978-01-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-2-isocyanopupukeanane,,10.1016/s0040-4039(01)86404-2,1979-01-01,0.585130102153097
Tetrahedron,"The total synthesis of the 4,5-dioxoaporphine alkaloid pontevedrine",,10.1016/s0040-4039(01)86839-8,1978-01-01,0.585130102153097
Tetrahedron,Total synthesis of juncusol,,10.1016/s0040-4039(01)85715-4,1978-01-01,0.585130102153097
Tetrahedron,Total synthesis of juncusol,,10.1016/s0040-4039(01)94923-8,1978-01-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-Anastatins A and B,,10.1016/j.tetlet.2015.05.096,2015-05-31,0.585130102153097
Tetrahedron,Total synthesis of gibberellin A4,,10.1016/s0040-4039(00)77864-6,1980-01-01,0.585130102153097
Tetrahedron,"Total Synthesis of Cystodytin J, Diplamine and Shermilamine B",,10.1016/00404-0399(50)08487-,1995-07-03,0.585130102153097
Tetrahedron,"Total synthesis of an acaricide, Gualamycin",,10.1016/00404-0399(50)1360-t,1995-09-01,0.585130102153097
Tetrahedron,Total synthesis of nonactin,,10.1016/0040-4039(95)00541-j,1995-05-01,0.585130102153097
Tetrahedron,The first total synthesis of preverecynarmin,,10.1016/s0040-4039(99)00124-0,1999-03-01,0.585130102153097
Tetrahedron,"First total synthesis of (±)-β-microbiotene, (±)-microbiotol and (±)-cyclocuparenol",,10.1016/s0040-4039(99)01342-8,1999-09-01,0.585130102153097
Tetrahedron,Total synthesis of (−)-tamandarin B,,10.1016/s0040-4039(00)01409-x,2000-12-01,0.585130102153097
Tetrahedron,Total synthesis of L-capreomycidine,,10.1016/s0040-4039(01)83045-8,1977-01-01,0.585130102153097
Organic Letters,Correction to Total Synthesis of (–)-Amphidinolide P,Correction to Total Synthesis of (,10.1021/ol400833j,2013-04-03,0.585130102153097
Tetrahedron,Total synthesis of pseudopterosin A and E aglycon,,10.1016/0040-4039(95)01981-m,1995-12-01,0.585130102153097
Tetrahedron,Total synthesis and unambiguous stereochemical assignment of disodium prephenate,,10.1016/s0040-4039(01)95011-7,1978-01-01,0.585130102153097
Tetrahedron,Total synthesis of (+)-decytospolides A and B,,10.1016/j.tetlet.2015.04.055,2015-04-28,0.585130102153097
Tetrahedron,The first total synthesis of (+)-(Z)-laureatin,,10.1016/j.tetlet.2006.12.082,2007-01-09,0.585130102153097
Tetrahedron,Total synthesis of conolidine and apparicine,,10.1016/j.tetlet.2015.12.029,2015-12-17,0.585130102153097
Tetrahedron,Total Synthesis of Hemibrevetoxin B,,10.1016/00404-0399(50)10972-,1995-08-07,0.585130102153097
Tetrahedron,"Total synthesis of ovalifoliolatin B, acerogenins A and C",,10.1016/j.tetlet.2008.01.135,2008-02-07,0.585130102153097
Tetrahedron,The first total synthesis of telephiose A,,10.1016/j.tetlet.2007.03.138,2007-03-28,0.585130102153097
Synlett,Formal Total Synthesis of Clausenamide,,10.1055/s-1991-20723,1991-01-01,0.585130102153097
Tetrahedron,Total synthesis of AI-77-B,,10.1016/j.tetlet.2014.09.009,2014-09-16,0.585130102153097
Tetrahedron,Total synthesis of catenioblin B,,10.1016/j.tetlet.2014.09.034,2014-09-16,0.585130102153097
Tetrahedron,Total synthesis of isocladosporin and 3- epi -isocladosporin,,10.1016/j.tetlet.2015.11.060,2015-11-22,0.585130102153097
Tetrahedron,A regiospecific total synthesis of (±)-daunomycinone,,10.1016/s0040-4039(01)86102-5,1979-01-01,0.585130102153097
Tetrahedron,"The total synthesis of (±)-friedelin, an unsymmetrical, pentacyclic triterpene",,10.1016/s0040-4039(00)93753-5,1976-04-01,0.585130102153097
Tetrahedron,Total Synthesis of (±)-Nanaomycin A and (±)-Frenolicin,,10.1016/s0040-4039(00)92203-2,1980-01-01,0.585130102153097
Tetrahedron,Total synthesis of picrotin,,10.1016/s0040-4039(00)92789-8,1980-01-01,0.585130102153097
Tetrahedron,Total synthesis of tovophyllin B,,10.1016/j.tetlet.2008.12.096,2008-12-26,0.585130102153097
Tetrahedron,The first total synthesis of glycyrol,,10.1016/j.tetlet.2008.09.070,2008-09-18,0.585130102153097
Tetrahedron,Total synthesis of the marine pyrroloiminoquinone alkaloid tsitsikammamine A,,10.1016/j.tetlet.2008.12.078,2008-12-25,0.585130102153097
Tetrahedron,Total synthesis of (−)-xanthatin,,10.1016/j.tetlet.2008.03.081,2008-03-21,0.585130102153097
Tetrahedron,A total synthesis of (±)-frondosins A and B,,10.1016/j.tetlet.2008.09.163,2008-10-03,0.585130102153097
Tetrahedron,Total synthesis of 5-epikessane and dehydrokessane,,10.1016/s0040-4039(01)83330-x,1977-01-01,0.585130102153097
Tetrahedron,The total synthesis of (±)-puupehenone,,10.1016/s0040-4039(01)94594-0,1978-01-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-anhydrolycodoline and (±)-lycopodine,,10.1016/s0040-4039(01)91516-3,1978-01-01,0.585130102153097
Tetrahedron,First total synthesis of prunustatin A,,10.1016/j.tetlet.2013.12.106,2014-01-04,0.585130102153097
Tetrahedron,The total synthesis of (±) - ptilocaulin,,10.1016/s0040-4039(00)81549-x,1983-01-01,0.585130102153097
Tetrahedron,Formal total synthesis of enigmazole A,,10.1016/j.tetlet.2018.11.017,2018-11-09,0.585130102153097
Tetrahedron,First total synthesis of versicotide D and analogs,,10.1016/j.tetlet.2019.151281,2019-10-14,0.585130102153097
Tetrahedron,Total synthesis of kehokorins A and B,,10.1016/j.tetlet.2019.04.011,2019-04-03,0.585130102153097
Tetrahedron,Enantiospecific total synthesis of (−)-crotanecine,,10.1016/j.tetlet.2017.08.056,2017-08-24,0.585130102153097
Tetrahedron,A brief total synthesis of Pyrrolostatin,,10.1016/j.tetlet.2016.05.010,2016-05-11,0.585130102153097
Tetrahedron,Total synthesis of bastadins,,10.1016/s0040-4039(00)87083-5,1982-01-01,0.585130102153097
Tetrahedron,Total synthesis of (−)-haploscleridamine,,10.1016/j.tetlet.2019.03.004,2019-03-02,0.585130102153097
Tetrahedron,Total synthesis of Tasimelteon,,10.1016/j.tetlet.2019.06.048,2019-06-25,0.585130102153097
Tetrahedron,First total synthesis of Brevipolide N and total synthesis of Brevipolide M,,10.1016/j.tetlet.2018.10.018,2018-10-11,0.585130102153097
Tetrahedron,First total synthesis of haplacutine C,,10.1016/j.tetlet.2016.10.070,2016-10-21,0.585130102153097
Tetrahedron,Total synthesis of (±)-decarbomethoxynauclechine,,10.1016/s0040-4039(00)85741-x,1982-01-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-eremolactone,,10.1016/s0040-4039(00)94059-0,1983-01-01,0.585130102153097
Tetrahedron,Total synthesis of leukotriene B5,,10.1016/s0040-4039(01)99801-6,1983-01-01,0.585130102153097
Tetrahedron,First total synthesis of Pestalotioprolide C and its C7 epimer,,10.1016/j.tetlet.2017.02.019,2017-02-10,0.585130102153097
Tetrahedron,Total synthesis of deglyco-bleomycin A2,,10.1016/s0040-4039(01)92519-5,1981-01-01,0.585130102153097
Tetrahedron,The total synthesis of (±)-C-mavacurine,,10.1016/s0040-4039(01)90397-1,1981-01-01,0.585130102153097
Tetrahedron,"Total synthesis of (±)-xanthocidin and (±)-desdihydroxy-4,5-dihydroxanthocidin",,10.1016/s0040-4039(01)82006-2,1981-01-01,0.585130102153097
Tetrahedron,Total synthesis of obtusenol,,10.1016/s0040-4039(01)92422-0,1981-01-01,0.585130102153097
Tetrahedron,"Total synthesis of tylonolide, an aglycone of tylosin",,10.1016/s0040-4039(01)82047-5,1981-01-01,0.585130102153097
Tetrahedron,"Total synthesis of (±)-desepoxy-4,5-didehybromethylenomycin A",,10.1016/0040-4039(81)80029-9,1981-01-01,0.585130102153097
Tetrahedron,A biogenetically patterned total synthesis of prostaglandin E1,,10.1016/s0040-4039(00)87271-8,1982-01-01,0.585130102153097
Tetrahedron,Total synthesis of (+)-conagenin,,10.1016/j.tetlet.2006.06.087,2006-07-06,0.585130102153097
Tetrahedron,Total synthesis of (+)-monacolin K (mevinolin),,10.1016/s0040-4039(00)81777-3,1983-01-01,0.585130102153097
Tetrahedron,Cannabis XXVI. Total synthesis of cannabifuran,,10.1016/s0040-4039(00)81338-6,1983-01-01,0.585130102153097
Tetrahedron,The total synthesis of cannithrene-2,,10.1016/s0040-4039(00)87884-3,1983-01-01,0.585130102153097
Tetrahedron,Total synthesis of the tricyclic humulanolide wilfolide B,,10.1016/j.tetlet.2019.06.058,2019-06-26,0.585130102153097
Tetrahedron,Total synthesis of siomycin A,,10.1016/j.tetlet.2006.12.121,2006-12-26,0.585130102153097
Tetrahedron,Total synthesis of (−)-clavosolide A,,10.1016/j.tetlet.2006.08.055,2006-09-08,0.585130102153097
Tetrahedron,A formal total synthesis of crocacin C,,10.1016/j.tetlet.2006.10.141,2006-11-20,0.585130102153097
Tetrahedron,First total synthesis of topopyrone C,,10.1016/j.tetlet.2006.11.164,2006-12-23,0.585130102153097
Tetrahedron,Total synthesis of (−)-radicamine B,,10.1016/j.tetlet.2006.07.120,2006-08-18,0.585130102153097
Tetrahedron,Total synthesis of (−)-neplanocin A,,10.1016/s0040-4039(00)94140-6,1983-01-01,0.585130102153097
Tetrahedron,Guaianolides : The total synthesis of (±)-estafiatin,,10.1016/s0040-4039(00)87380-3,1982-01-01,0.585130102153097
Tetrahedron,Regiospecific total synthesis of juncusol,,10.1016/s0040-4039(00)85652-x,1982-01-01,0.585130102153097
Tetrahedron,The first total synthesis of usabamycins a and C,,10.1016/j.tetlet.2017.05.020,2017-05-11,0.585130102153097
Tetrahedron,Total synthesis of chrysamide B,,10.1016/j.tetlet.2017.04.079,2017-04-26,0.585130102153097
Tetrahedron,Total synthesis of greensporone C,,10.1016/j.tetlet.2017.07.074,2017-07-23,0.585130102153097
Tetrahedron,Formal total synthesis of stigmatellin A,,10.1016/j.tetlet.2017.08.048,2017-08-21,0.585130102153097
Tetrahedron,A straight forward and first total synthesis of Penilumamides B–D,,10.1016/j.tetlet.2017.07.027,2017-07-13,0.585130102153097
Tetrahedron,Total synthesis of Carpatamides A–D,,10.1016/j.tetlet.2018.05.090,2018-05-31,0.585130102153097
Tetrahedron,Total synthesis of janadolide,,10.1016/j.tetlet.2018.02.034,2018-02-21,0.585130102153097
Tetrahedron,Total synthesis of JBIR-03 and asporyzin C,,10.1016/j.tetlet.2018.10.009,2018-10-06,0.585130102153097
Tetrahedron,Total synthesis of (S)-(−)-cyclooroidin,,10.1016/j.tetlet.2006.05.130,2006-06-19,0.585130102153097
Tetrahedron,Total synthesis of (−)-vermiculine,,10.1016/0040-4039(94)88291-6,1994-10-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-allo-cedrol [Khusiol],,10.1016/s0040-4039(00)73318-1,1994-07-01,0.585130102153097
Tetrahedron,Total synthesis of PI-091,,10.1016/0040-4039(95)01049-n,1995-07-01,0.585130102153097
Synthesis,Total Synthesis of Uracil Polyoxin C,,10.1055/s-1998-4499,1998-10-01,0.585130102153097
Tetrahedron,Total synthesis of madindoline A,,10.1016/s0040-4039(00)00939-4,2000-08-01,0.585130102153097
Tetrahedron,Total synthesis of the marine sesquiterpene hydroquinones zonarol and isozonarol and the sesquiterpene quinones zonarone and isozonarone,,10.1016/s0040-4039(00)00891-1,2000-07-01,0.585130102153097
Tetrahedron,First total synthesis of the marine alkaloids purpurone and ningalin C,,10.1016/s0040-4039(00)01614-2,2000-12-01,0.585130102153097
Tetrahedron,Total synthesis of neodolabellenol,,10.1016/0040-4039(94)02163-6,1995-01-01,0.585130102153097
Angewandte Chemie International Edition,Total Synthesis of Bryostatin 3,,10.1002/1521-3773(20000703)39:13<2290::aid-anie2290>3.3.co;2-y,2000-07-03,0.585130102153097
Tetrahedron,"Total synthesis of (10ξ,15R,16S,19S,20S,34R)-Corossoline",,10.1016/0040-4039(94)88189-8,1994-01-01,0.585130102153097
Tetrahedron,Total synthesis of (+)-obtusenyne,,10.1016/j.tetlet.2006.11.080,2006-12-13,0.585130102153097
Tetrahedron,Total synthesis of thymine polyoxin C,,10.1016/s0040-4039(00)78564-9,1994-12-01,0.585130102153097
Tetrahedron,A total synthesis of (−)-antimycin A3b,,10.1016/s0040-4039(00)01316-2,2000-09-01,0.585130102153097
Tetrahedron,A stereocontrolled total synthesis of (±)-norzizanone,,10.1016/s0040-4039(00)01861-x,2000-12-01,0.585130102153097
Tetrahedron,"Total synthesis of a marine alkaloid, rigidin",,10.1016/s0040-4039(00)76660-3,1994-05-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-9-deoxygoniopypyrone,,10.1016/s0040-4039(00)77261-3,1994-08-01,0.585130102153097
Tetrahedron,The first total synthesis of phomopsolidone A,,10.1016/j.tetlet.2016.04.004,2016-04-03,0.585130102153097
Tetrahedron,"Total synthesis of (3R,5R) and (3R,5S)-sonnerlactones",,10.1016/j.tetlet.2016.03.030,2016-03-10,0.585130102153097
Tetrahedron,"Total synthesis of (–)-(3R,6S,9R)-decarestrictine C2",,10.1016/s0040-4039(99)02138-3,2000-02-01,0.585130102153097
Tetrahedron,"Total synthesis of penipanoid C, 2-(4-hydroxybenzyl)quinazolin-4(3H)-one and NU1025",,10.1016/j.tetlet.2016.08.018,2016-08-09,0.585130102153097
Tetrahedron,First total synthesis of 6-epi-phomonol,,10.1016/j.tetlet.2016.05.006,2016-05-04,0.585130102153097
Tetrahedron,Total synthesis of mirabazole B,,10.1016/s0040-4039(00)76224-1,1994-02-01,0.585130102153097
Tetrahedron,The first enantiospecific total synthesis of (+)-seychellene,,10.1016/j.tetlet.2006.11.011,2006-11-22,0.585130102153097
Tetrahedron,"Total synthesis of d,1-megaphone",,10.1016/s0040-4039(00)86382-0,1983-01-01,0.585130102153097
Tetrahedron,Total synthesis of -methylpallidinine,,10.1016/s0040-4039(00)86218-8,1983-01-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-silphinene,,10.1016/s0040-4039(00)81333-7,1983-01-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-talaromycin B,,10.1016/s0040-4039(00)94006-1,1983-01-01,0.585130102153097
Tetrahedron,Total synthesis of distaminolyne A,,10.1016/j.tetlet.2017.02.029,2017-02-13,0.585130102153097
Tetrahedron,Total synthesis of (+)-blennolide C and (+)-gonytolide C via spirochromanone,,10.1016/j.tetlet.2017.10.038,2017-10-16,0.585130102153097
Tetrahedron,"A total synthesis of (±)faranal, the true trail pheromone of pharaoh's ant,",,10.1016/s0040-4039(01)92431-1,1981-01-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-spirolaurenone,,10.1016/s0040-4039(00)88440-3,1982-01-01,0.585130102153097
Tetrahedron,Total synthesis of bleomycin A21),,10.1016/s0040-4039(00)86878-1,1982-01-01,0.585130102153097
Tetrahedron,"Total synthesis of the disaccharide of bleomycin, 2-0-(α--mannopyranosyl)--gulopyranose",,10.1016/s0040-4039(01)90336-3,1981-01-01,0.585130102153097
Tetrahedron,Total synthesis of pleurolactone,,10.1016/j.tetlet.2017.07.028,2017-07-08,0.585130102153097
Tetrahedron,First total synthesis of (−)-salprzelactone,,10.1016/j.tetlet.2017.03.072,2017-03-24,0.585130102153097
Tetrahedron,Total synthesis of actinophenanthroline A,,10.1016/j.tetlet.2016.04.019,2016-04-10,0.585130102153097
Tetrahedron,The first total synthesis of (S)-clavulazine from d-mannitol,,10.1016/j.tetlet.2006.08.006,2006-08-25,0.585130102153097
Tetrahedron,Total synthesis of tetraacetyl clionamide,,10.1016/s0040-4039(00)85745-7,1982-01-01,0.585130102153097
Tetrahedron,Total synthesis of catalpalactone,,10.1016/s0040-4039(00)85627-0,1982-01-01,0.585130102153097
Tetrahedron,Total synthesis of (-oudemansin,,10.1016/s0040-4039(00)87009-4,1982-01-01,0.585130102153097
Tetrahedron,"Total synthesis of d,1-occidentalol by photoannelation",,10.1016/s0040-4039(00)85623-3,1982-01-01,0.585130102153097
Tetrahedron,A total synthesis of leukotriene F4 (LTF4),,10.1016/s0040-4039(00)88671-2,1982-01-01,0.585130102153097
Tetrahedron,The first total synthesis of sporiolide B,,10.1016/j.tetlet.2006.09.145,2006-10-18,0.585130102153097
Tetrahedron,The first total synthesis of (±)-lagopodin A,,10.1016/j.tetlet.2005.12.071,2006-01-11,0.585130102153097
Tetrahedron,Total synthesis of tylosin,,10.1016/s0040-4039(00)87619-4,1982-01-01,0.585130102153097
Tetrahedron,Total synthesis of pyroangolensolide,,10.1016/s0040-4039(01)87359-7,1973-01-01,0.585130102153097
Tetrahedron,The total synthesis of (±)-ochotensimine,,10.1016/s0040-4039(00)76147-8,1968-01-01,0.585130102153097
Tetrahedron,The total synthesis of d1-epiibogamine,,10.1016/s0040-4039(00)89499-x,1968-01-01,0.585130102153097
Tetrahedron,Total synthesis of cyclosativene,,10.1016/s0040-4039(01)97651-8,1969-01-01,0.585130102153097
Tetrahedron,Total synthesis of the host defense stimulant maesanin,,10.1016/0040-4039(90)80007-9,1990-01-01,0.585130102153097
Tetrahedron,Total synthesis of isorobustin,,10.1016/s0040-4039(00)88512-3,1990-01-01,0.585130102153097
Tetrahedron,First total synthesis of dl-duocarmycin A,,10.1016/s0040-4039(00)97151-x,1990-01-01,0.585130102153097
Tetrahedron,The total synthesis of oleandomycin,,10.1016/s0040-4039(00)94609-4,1990-01-01,0.585130102153097
Tetrahedron,Total synthesis of (+)-phyllanthocindiol and (+)-phyllanthostatin 3,,10.1016/s0040-4039(00)99491-7,1989-01-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-neplanocin F,,10.1016/s0040-4039(01)80539-6,1989-01-01,0.585130102153097
Tetrahedron,Total synthesis of β-pinguisene,,10.1016/0040-4039(95)00669-4,1995-06-01,0.585130102153097
Tetrahedron,Total synthesis of cytotoxic sponge alkaloids motuporamines A and B,,10.1016/s0040-4039(99)01016-3,1999-07-01,0.585130102153097
Tetrahedron,Enantiospecific first total synthesis of (−)-4-thiocyanatoneopupukeanane,,10.1016/s0040-4039(98)02522-2,1999-01-01,0.585130102153097
Tetrahedron,Total synthesis of pristinamycin IIB,,10.1016/s0040-4039(98)00499-7,1998-05-01,0.585130102153097
Tetrahedron,Total synthesis of didemnimide A and B,,10.1016/s0040-4039(98)02211-4,1998-12-01,0.585130102153097
Tetrahedron,Total synthesis of (−)-pironetin,,10.1016/s0040-4039(98)01860-7,1998-11-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-TAN1251A,,10.1016/s0040-4039(98)00797-7,1998-06-01,0.585130102153097
Tetrahedron,Total synthesis of asterriquinone B1,,10.1016/s0040-4039(99)00965-x,1999-07-01,0.585130102153097
Tetrahedron,"Total synthesis of an extended ganglio-ganglioside, IV4GalNAcβGm1b1)",,10.1016/s0040-4039(00)88826-7,1990-01-01,0.585130102153097
Tetrahedron,First total synthesis of (−)-8-epi-9-deoxygoniopypyrone,,10.1016/s0040-4039(98)02269-2,1998-12-01,0.585130102153097
Tetrahedron,Total synthesis of (+)-homopumiliotoxin 223G,,10.1016/s0040-4039(98)00082-3,1998-04-01,0.585130102153097
Tetrahedron,"A total synthesis of Forssman glycolipid, globopentaosyl ceramide",,10.1016/s0040-4039(00)70658-7,1989-01-01,0.585130102153097
Tetrahedron,The total synthesis of (±)-mesembrine,,10.1016/s0040-4039(01)89046-8,1965-01-01,0.585130102153097
Tetrahedron,The total synthesis of (±)-hibaene,,10.1016/s0040-4039(00)90219-3,1965-01-01,0.585130102153097
Tetrahedron,Stereochemical relationships in spirovetivane sesquiterpenes: The total synthesis of hinesol,,10.1016/s0040-4039(01)87894-1,1969-01-01,0.585130102153097
Tetrahedron,The total synthesis of dl-cepharamine,,10.1016/s0040-4039(01)87959-4,1969-01-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-antofine,,10.1016/j.tetlet.2013.10.124,2013-11-04,0.585130102153097
Synlett,Total Synthesis of (+) and (-)-Furocaulerpin,International audience,10.1055/s-2002-25353,2002-01-01,0.585130102153097
Tetrahedron,Stereoflexible total synthesis of (−)-epiquinamide,,10.1016/j.tetlet.2009.02.051,2009-02-13,0.585130102153097
Tetrahedron,First total synthesis of (+)-crassalactone A,,10.1016/j.tetlet.2009.12.038,2009-12-17,0.585130102153097
Tetrahedron,Total synthesis of polemannones B and C,,10.1016/j.tetlet.2009.04.043,2009-04-15,0.585130102153097
Tetrahedron,First total synthesis of theopederin B,,10.1016/j.tetlet.2009.03.066,2009-03-17,0.585130102153097
Tetrahedron,Total synthesis of DL-camptothecin from furfural,,10.1016/s0040-4039(01)95926-x,1973-01-01,0.585130102153097
Tetrahedron,Total synthesis of amurine,,10.1016/s0040-4039(01)88202-2,1969-01-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-steviol,,10.1016/s0040-4039(01)98242-5,1970-01-01,0.585130102153097
Tetrahedron,The total synthesis of dl-hasubanonine,,10.1016/s0040-4039(00)89353-3,1970-01-01,0.585130102153097
Tetrahedron,Total synthesis of copacamphene,,10.1016/s0040-4039(01)98574-0,1970-01-01,0.585130102153097
Tetrahedron,Total synthesis of amurine,,10.1016/s0040-4039(00)89803-2,1968-01-01,0.585130102153097
Tetrahedron,The total synthesis of (±)-eremophilene and (±)-eremoligenol,,10.1016/s0040-4039(00)89790-7,1968-01-01,0.585130102153097
Tetrahedron,Total synthesis of -elemol,,10.1016/s0040-4039(01)88010-2,1969-01-01,0.585130102153097
Tetrahedron,"Total synthesis of (15S, 16R, 19S, 20R, 34S)-diepomuricanin",,10.1016/0040-4039(96)01086-6,1996-07-01,0.585130102153097
Tetrahedron,The total synthesis of (±)bakkenolide-A,,10.1016/s0040-4039(01)87311-1,1973-01-01,0.585130102153097
Tetrahedron,Total synthesis of polyoxin J,,10.1016/s0040-4039(01)87647-4,1973-01-01,0.585130102153097
Tetrahedron,The total synthesis of samanine,,10.1016/s0040-4039(01)87840-0,1969-01-01,0.585130102153097
Tetrahedron,Total synthesis of (±)--methylsterigmatocystin,,10.1016/s0040-4039(01)98344-3,1970-01-01,0.585130102153097
Tetrahedron,Total synthesis of kanamycin-A,,10.1016/s0040-4039(01)98818-5,1968-01-01,0.585130102153097
Journal of the American Chemical Society,"Correction to “Total Synthesis of Psammaplysins A, M, O, and Q and Ceratinamide A”",,10.1021/jacs.4c10840,2024-09-03,0.585130102153097
Tetrahedron,A total synthesis of d1-eburnamonine,,10.1016/s0040-4039(01)99479-1,1959-01-01,0.585130102153097
Tetrahedron,The total synthesis of 8-isotestosterone,,10.1016/s0040-4039(01)99308-6,1960-01-01,0.585130102153097
Tetrahedron,The total synthesis of (±)-widdrol,,10.1016/s0040-4039(00)70854-9,1962-01-01,0.585130102153097
Tetrahedron,First total synthesis of astin G,,10.1016/s0040-4039(98)02423-x,1999-01-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-pterocarpin and (±)-pisatin,,10.1016/s0040-4039(01)99800-4,1966-01-01,0.585130102153097
Tetrahedron,Total synthesis of hydroechinuline.,,10.1016/0040-4039(64)83058-6,1964-01-01,0.585130102153097
Tetrahedron,Total synthesis of aspidospermine,,10.1016/s0040-4039(00)70368-6,1965-01-01,0.585130102153097
Tetrahedron,Total synthesis of sulfobacin A (flavocristamide B),,10.1016/s0040-4039(98)01177-0,1998-08-01,0.585130102153097
Tetrahedron,Total synthesis of arenamide A and its diastereomer,,10.1016/j.tetlet.2009.09.119,2009-09-26,0.585130102153097
Tetrahedron,Total synthesis of isoroquefortine E and phenylahistin,,10.1016/j.tetlet.2009.09.074,2009-09-26,0.585130102153097
Tetrahedron,Total synthesis of (±)-megistophylline I,,10.1016/j.tetlet.2009.03.157,2009-03-30,0.585130102153097
Tetrahedron,Total synthesis of fuligocandines A and B,,10.1016/j.tetlet.2009.10.134,2009-11-05,0.585130102153097
Tetrahedron,Total Synthesis of Erosnin,,10.1016/s0040-4039(00)90207-7,1965-01-01,0.585130102153097
Tetrahedron,Total synthesis of α-santalol,,10.1016/s0040-4039(00)90958-4,1967-01-01,0.585130102153097
Tetrahedron,The total synthesis of chamaecynone,,10.1016/s0040-4039(00)90866-9,1967-01-01,0.585130102153097
Tetrahedron,Total synthesis of albonoursin,,10.1016/s0040-4039(01)89564-2,1967-01-01,0.585130102153097
Tetrahedron,First total synthesis and stereochemical revision of okaramine M,,10.1016/j.tetlet.2010.09.026,2010-09-18,0.585130102153097
Tetrahedron,Total synthesis of 4-F3t-neuroprostane and its 4-epimer,,10.1016/j.tetlet.2009.01.075,2009-01-20,0.585130102153097
Tetrahedron,Total synthesis of Eudistomins Y1–Y6,,10.1016/j.tetlet.2009.09.180,2009-10-05,0.585130102153097
Tetrahedron,The first total synthesis of (±)-ribasine,,10.1016/s0040-4039(97)10778-x,1998-03-01,0.585130102153097
Tetrahedron,The enantiospecific total synthesis of norsuaveoline,,10.1016/s0040-4039(98)01788-2,1998-10-01,0.585130102153097
Journal of Organic Chemistry,Total Synthesis of (â)-Sessilifoliamide J,,,2013-01-01,0.585130102153097
Tetrahedron,The first total synthesis of sideroxylonal B,,10.1016/s0040-4039(99)00045-3,1999-03-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-Sinaiticin,,10.1016/s0040-4039(99)00792-3,1999-06-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-dauricine,,10.1016/s0040-4039(00)71728-x,1964-01-01,0.585130102153097
Tetrahedron,Total synthesis of -corynantheine,,10.1016/0040-4039(64)80014-9,1964-01-01,0.585130102153097
Tetrahedron,A total synthesis of (±)-cularimine,,10.1016/s0040-4039(01)89317-5,1964-01-01,0.585130102153097
Tetrahedron,Total synthesis of angolide,,10.1016/0040-4039(64)83090-2,1964-01-01,0.585130102153097
Tetrahedron,The total synthesis of dl-rimuene,,10.1016/s0040-4039(01)89410-7,1964-01-01,0.585130102153097
Tetrahedron,First total synthesis of achaetolide,,10.1016/j.tetlet.2010.07.127,2010-07-30,0.585130102153097
Tetrahedron,A total synthesis of diterpene alkaloids,,10.1016/s0040-4039(00)75715-7,1966-01-01,0.585130102153097
Tetrahedron,Total synthesis of dl-elaeocarpine and dl-isoelaeocarpine,,10.1016/s0040-4039(01)98640-x,1970-01-01,0.585130102153097
Tetrahedron,Total synthesis of arcyroxocin A,,10.1016/0040-4039(96)00864-7,1996-06-01,0.585130102153097
Tetrahedron,Total synthesis of (−)-cordiaquinone B,,10.1016/0040-4039(96)01556-0,1996-09-01,0.585130102153097
Tetrahedron,Total synthesis of the cyclodepsipeptide ionophore pithomycolide,,10.1016/0040-4039(96)01421-9,1996-09-01,0.585130102153097
Tetrahedron,"Enantiocontrolled total synthesis of the diterpenoids, triptoquinone B, C and triptocallol",,10.1016/s0040-4039(97)00841-1,1997-06-01,0.585130102153097
Tetrahedron,First total synthesis of (±)-brasiliquinone B,,10.1016/s0040-4039(99)00766-2,1999-06-01,0.585130102153097
Tetrahedron,"First total synthesis of tetrasubstituted tetrahydrofuran lignan, (−)-virgatusin",,10.1016/s0040-4039(99)00848-5,1999-06-01,0.585130102153097
Tetrahedron,Total synthesis of (+)-breynolide,,10.1016/s0040-4039(98)80004-x,1999-01-01,0.585130102153097
Tetrahedron,First total synthesis of (−)-α-conidendrin,,10.1016/s0040-4039(00)99363-8,1989-01-01,0.585130102153097
Tetrahedron,The total synthesis of phyllocladene,,10.1016/s0040-4039(01)84051-x,1961-01-01,0.585130102153097
Tetrahedron,Total synthesis of mycestericin A,,10.1016/j.tetlet.2008.01.105,2008-01-31,0.585130102153097
Tetrahedron,Total synthesis of (+)-epiquinamide from d-mannitol,,10.1016/j.tetlet.2008.11.115,2008-12-05,0.585130102153097
Tetrahedron,The total synthesis of (±)-seychellene,,10.1016/s0040-4039(01)98435-7,1970-01-01,0.585130102153097
Tetrahedron,Total synthesis of -illudol,,10.1016/s0040-4039(01)97221-1,1971-01-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-epicrinine by photolysis,,10.1016/s0040-4039(01)97117-5,1971-01-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-fukinone,,10.1016/s0040-4039(01)96547-5,1971-01-01,0.585130102153097
Tetrahedron,A total synthesis of (±)-occidentalol,,10.1016/s0040-4039(01)94389-8,1972-01-01,0.585130102153097
Tetrahedron,Total synthesis of dl-metaphanine,,10.1016/s0040-4039(01)84637-2,1972-01-01,0.585130102153097
Tetrahedron,The first total synthesis of emericellamide A,,10.1016/j.tetlet.2008.03.107,2008-03-29,0.585130102153097
Tetrahedron,"First total synthesis of sterenins A, C and D",,10.1016/j.tetlet.2008.01.031,2008-01-12,0.585130102153097
Tetrahedron,Total synthesis of quebecol,,10.1016/j.tetlet.2013.07.048,2013-07-15,0.585130102153097
Tetrahedron,Toward the total synthesis of ansalactam A,,10.1016/j.tetlet.2013.10.104,2013-10-30,0.585130102153097
Tetrahedron,First total synthesis of piperodione and analogs,,10.1016/j.tetlet.2014.09.079,2014-09-20,0.585130102153097
Tetrahedron,Total synthesis of mangiferaelactone,,10.1016/j.tetlet.2014.09.084,2014-09-28,0.585130102153097
Tetrahedron,Total synthesis of antifungal gamahonolide A,,10.1016/j.tetlet.2014.04.026,2014-04-18,0.585130102153097
Tetrahedron,Total synthesis of lansiumamides A and B and alatamide,,10.1016/j.tetlet.2014.09.008,2014-09-16,0.585130102153097
Tetrahedron,Total synthesis of deoxyvernolepin,,10.1016/s0040-4039(00)91151-1,1975-01-01,0.585130102153097
Tetrahedron,The total synthesis of the alkaloid (±)-1-acetylaspidoalbidine,,10.1016/s0040-4039(00)71968-x,1975-01-01,0.585130102153097
Tetrahedron,"Total synthesis of (±)-isopetasol, (±)-3-epiisopetasol, and (±)-warburgiadion",,10.1016/s0040-4039(01)93172-7,1974-01-01,0.585130102153097
Tetrahedron,Total synthesis of portulal,,10.1016/s0040-4039(00)91348-0,1975-01-01,0.585130102153097
Tetrahedron,Total synthesis of prostaglandin D2,,10.1016/s0040-4039(01)92221-x,1974-01-01,0.585130102153097
Tetrahedron,A total synthesis of (+)-isolaurepan,,10.1016/j.tetlet.2008.09.134,2008-09-27,0.585130102153097
Tetrahedron,"Total synthesis of (±)-heliannuol D, an allelochemical from Helianthus annuus",,10.1016/s0040-4039(99)02284-4,2000-02-01,0.585130102153097
Tetrahedron,"Total synthesis of (2S,3S,4R)-plakoridine A",,10.1016/s0040-4039(00)00096-4,2000-03-01,0.585130102153097
Tetrahedron,"The polyhydroxy cyclopentene, a total synthesis of (-)-pentenomycin",,10.1016/s0040-4039(00)00628-6,2000-06-01,0.585130102153097
Synthesis,Tetraquinane Diterpenoids: Total Synthesis of (±)-Crinipellin B,,10.1055/s-1998-5925,1998-03-01,0.585130102153097
Tetrahedron,Towards the total synthesis of clavosolide A,,10.1016/j.tetlet.2006.03.107,2006-04-13,0.585130102153097
Tetrahedron,Total synthesis of koninginin a and its diastereoisomer,,10.1016/0040-4039(95)02037-p,1995-12-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-strobilurin E,,10.1016/0040-4039(96)01833-3,1996-10-01,0.585130102153097
Tetrahedron,Total synthesis of (±) epibatidine,,10.1016/0040-4039(96)00042-1,1996-02-01,0.585130102153097
Tetrahedron,Total synthesis of (+)-Eurylene,,10.1016/0040-4039(96)00212-2,1996-03-01,0.585130102153097
Tetrahedron,Total synthesis of (+)-allo-cedrol,,,1994-02-22,0.585130102153097
Tetrahedron,The total synthesis of favelanone,,10.1016/s0040-4039(96)01482-7,1996-09-01,0.585130102153097
Tetrahedron,The total synthesis of (±)K252a,,10.1016/0040-4039(95)01811-u,1995-11-01,0.585130102153097
Tetrahedron,A total synthesis of (+)-eremantholide A,,10.1016/0040-4039(95)00066-l,1995-02-01,0.585130102153097
Tetrahedron,Total synthesis of Hemibrevetoxin B,,10.1016/0040-4039(95)01097-2,1995-08-01,0.585130102153097
Tetrahedron,Total synthesis of ribostamycin,,10.1016/s0040-4039(00)77906-8,1976-02-01,0.585130102153097
Tetrahedron,Total synthesis of thromboxane B21,,10.1016/s0040-4039(00)93900-5,1976-09-01,0.585130102153097
Tetrahedron,"Total synthesis of bisbenzylisoquinoline alkaloids, trilobine and obaberine",,10.1016/s0040-4039(01)85520-9,1976-08-01,0.585130102153097
Tetrahedron,A total synthesis of α-damascones,,10.1016/s0040-4039(00)74613-2,1976-11-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-7-deoxydaunomycinone and (±)-7-deoxyisodaunomycinone,,10.1016/s0040-4039(00)93051-x,1976-09-01,0.585130102153097
Tetrahedron,"Total synthesis of dl-chamaecynone, a termiticidal norsesquiterpene",,10.1016/s0040-4039(01)83216-0,1977-01-01,0.585130102153097
Tetrahedron,Total synthesis of hemibrevetoxin B,,10.1016/0040-4039(96)01373-1,1996-08-01,0.585130102153097
Tetrahedron,Total synthesis of (+)-tautomycin,,10.1016/0040-4039(95)01436-l,1995-09-01,0.585130102153097
Tetrahedron,Total synthesis of (ent)-korupensamine D,,10.1016/0040-4039(96)00524-2,1996-04-01,0.585130102153097
Tetrahedron,The first total synthesis of pyralomicin 2c,,10.1016/s0040-4039(99)00046-5,1999-03-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-decaline,,10.1016/s0040-4039(01)96217-3,1973-01-01,0.585130102153097
Tetrahedron,A total synthesis of corunnine,,10.1016/s0040-4039(01)86986-0,1973-01-01,0.585130102153097
Tetrahedron,"A total synthesis of d,l-sporidesmin b",,10.1016/s0040-4039(01)93133-8,1974-01-01,0.585130102153097
Tetrahedron,Total synthesis of α-bisabolol-3-one and deodarone,,10.1016/s0040-4039(01)92026-x,1974-01-01,0.585130102153097
Tetrahedron,Total synthesis of resolvin E1,,10.1016/j.tetlet.2009.08.061,2009-08-24,0.585130102153097
Tetrahedron,Total synthesis of the cytotoxic alkaloid luotonin A,,10.1016/s0040-4039(98)02004-8,1998-12-01,0.585130102153097
Tetrahedron,Absolute stereostructure and total synthesis of leptomycin B,,10.1016/s0040-4039(98)01809-7,1998-11-01,0.585130102153097
Tetrahedron,First total synthesis of (±)-stachyflin,,10.1016/s0040-4039(98)00769-2,1998-06-01,0.585130102153097
Tetrahedron,Total synthesis of hyptolide,,10.1016/j.tetlet.2008.07.033,2008-07-10,0.585130102153097
Tetrahedron,Formal and total synthesis of (±)-cycloclavine,,10.1016/j.tetlet.2013.10.152,2013-11-06,0.585130102153097
Tetrahedron,First total synthesis of neurotrophic diacetylene tetrol (−)-petrosiol D,,10.1016/j.tetlet.2013.09.058,2013-09-21,0.585130102153097
Tetrahedron,Total synthesis of attenols A and B,,10.1016/j.tetlet.2013.08.043,2013-08-20,0.585130102153097
Tetrahedron,Total synthesis of (−)-Englerin A,,10.1016/j.tetlet.2014.01.012,2014-01-10,0.585130102153097
Tetrahedron,Total synthesis of ribisin A,,10.1016/j.tetlet.2013.12.052,2013-12-21,0.585130102153097
Tetrahedron,First total synthesis of aerucyclamide B,,10.1016/j.tetlet.2013.03.060,2013-03-24,0.585130102153097
Tetrahedron,Total synthesis of farylhydrazones A and B,,10.1016/j.tetlet.2012.06.012,2012-06-25,0.585130102153097
Tetrahedron,A total synthesis of dl-camptothecin,,10.1016/s0040-4039(01)85182-0,1972-01-01,0.585130102153097
Tetrahedron,A total synthesis of dl-velbanamine,,10.1016/s0040-4039(01)97261-2,1971-01-01,0.585130102153097
Tetrahedron,Enantiospecific first total synthesis of 7a(S)-p-hydroxyphenopyrrozin,,10.1016/j.tetlet.2012.01.098,2012-02-02,0.585130102153097
Tetrahedron,Total synthesis of fraxinellone,,10.1016/s0040-4039(01)94055-9,1972-01-01,0.585130102153097
Tetrahedron,The total synthesis of -yomogin,,10.1016/s0040-4039(00)71972-1,1975-01-01,0.585130102153097
Tetrahedron,The total synthesis of (±)-aspidofractinine,,10.1016/s0040-4039(00)93764-x,1976-04-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-brefeldin A,,10.1016/s0040-4039(00)93001-6,1976-12-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-lycoricidine,,10.1016/s0040-4039(00)75100-8,1975-01-01,0.585130102153097
Tetrahedron,A total synthesis of the alkaloid (±)-1-acetylaspidospermidine,,10.1016/s0040-4039(00)71967-8,1975-01-01,0.585130102153097
Tetrahedron,"Aspidosperma alkaloids: The total synthesis of (±)-N,O-diacetylcylindrocarpinol, (±)-cylindrocarine, (±)-cylindrocarpine, and (±)-cylindrocarpidine",,10.1016/s0040-4039(00)91203-6,1975-01-01,0.585130102153097
Tetrahedron,The total synthesis of (±)-decinine,,10.1016/s0040-4039(00)72348-3,1975-01-01,0.585130102153097
Tetrahedron,Total synthesis of DL-crotepoxide,,10.1016/s0040-4039(00)91451-5,1975-01-01,0.585130102153097
Tetrahedron,Total synthesis of AAL-toxin TA1,,10.1016/s0040-4039(99)01322-2,1999-09-01,0.585130102153097
Tetrahedron,Total synthesis of (±) indolmycin,,10.1016/0040-4039(96)01434-7,1996-09-01,0.585130102153097
Tetrahedron,Total synthesis of forskolin — Part I,,10.1016/0040-4039(95)02364-x,1996-02-01,0.585130102153097
Tetrahedron,Total synthesis of curacin A,,10.1016/0040-4039(95)02337-2,1996-02-01,0.585130102153097
Tetrahedron,Total synthesis of (+)-conagenin,,10.1016/0040-4039(96)00758-7,1996-06-01,0.585130102153097
Tetrahedron,Total synthesis of (+)-Indolizidine 195 B and (+)-Monomorine,,10.1016/0040-4039(95)02086-1,1996-01-01,0.585130102153097
Tetrahedron,"First total synthesis of (all-E)-(3S, 5R, 6R)-Paracentrone",,10.1016/0040-4039(96)00680-6,1996-05-01,0.585130102153097
Tetrahedron,A stereocontrolled total synthesis of (±)-Δ2-cedrene,,10.1016/0040-4039(96)00854-4,1996-06-01,0.585130102153097
Tetrahedron,Total synthesis of dolabellane diterpenoid claenone,,10.1016/s0040-4039(98)01385-9,1998-09-01,0.585130102153097
Tetrahedron,Total Synthesis of the Marine Alkaloid Hyellazole,,10.1016/00404-0399(50)1026e-,1995-07-24,0.585130102153097
Tetrahedron,"Total Synthesis of an Acaricide, Gualamycin",,10.1016/0040-4039(95)01360-t,1995-01-16,0.585130102153097
Tetrahedron,"Total Synthesis of an Acaricide, Gualamycin",,10.1016/00404-0399(50)1360t-,1995-09-11,0.585130102153097
Tetrahedron,Total synthesis of phomactin D,,10.1016/0040-4039(96)01585-7,1996-09-01,0.585130102153097
Tetrahedron,Total synthesis of (+)-goniodiol,,10.1016/0040-4039(95)02125-6,1996-01-01,0.585130102153097
Tetrahedron,Total synthesis of Leucinostatin D,,10.1016/s0040-4039(00)60915-2,1992-11-01,0.585130102153097
Tetrahedron,Formal total synthesis of (±)-herbertenediol and (±)-mastigophorenes A and B,,10.1016/s0040-4039(01)01109-1,2001-08-01,0.585130102153097
Tetrahedron,First total synthesis of (±)-tangutorine,,10.1016/s0040-4039(01)01310-7,2001-09-01,0.585130102153097
Tetrahedron,A total synthesis of (±)-epibatidine,,10.1016/s0040-4039(00)60162-4,1993-11-01,0.585130102153097
Tetrahedron,The total synthesis of D-mycinose,,10.1016/s0040-4039(00)82172-3,1988-01-01,0.585130102153097
Tetrahedron,Carbohydrates in total synthesis of (−)-antirhine,,10.1016/0040-4039(91)80018-2,1991-01-01,0.585130102153097
Tetrahedron,The total synthesis of radermachol,,10.1016/s0040-4039(00)92365-7,1991-09-01,0.585130102153097
Tetrahedron,Total synthesis of N-nornitidine,,10.1016/s0040-4039(00)93548-2,1991-10-01,0.585130102153097
Tetrahedron,Total synthesis of corallistin A,,10.1016/s0040-4039(00)92135-x,1991-01-01,0.585130102153097
Tetrahedron,Total synthesis of (−)-mintlactone,,10.1016/s0040-4039(00)93463-4,1991-09-01,0.585130102153097
Tetrahedron,"Total synthesis of cystodytin J, diplamine and shermilamine B",,10.1016/0040-4039(95)00848-7,1995-07-01,0.585130102153097
Tetrahedron,"First total synthesis of the 1,2,3,4-tetrahydronaphtho[2,1- f ]isoquinoline annoretine",,10.1016/s0040-4039(01)00168-x,2001-03-01,0.585130102153097
Tetrahedron,"Total synthesis of (+)-cheimonophyllon E, a bisabolane sesquiterpenoid",,10.1016/s0040-4039(01)00817-6,2001-07-01,0.585130102153097
Tetrahedron,Formal total synthesis of (±)-magellanine,,10.1016/s0040-4039(03)01516-8,2003-07-16,0.585130102153097
Tetrahedron,Total synthesis of the marine pyridoacridine alkaloid sebastianine A,,10.1016/s0040-4039(03)00320-4,2003-03-01,0.585130102153097
Synlett,Total Synthesis of (+)-Dodoneine,International audience,10.1055/s-2008-1078052,2008-09-12,0.585130102153097
Tetrahedron,Total synthesis of (±) - citreoviral,,10.1016/s0040-4039(00)87888-0,1988-01-01,0.585130102153097
Tetrahedron,An enantiospecific formal total synthesis of (−)-aplysin and (−)-debromoaplysin,,10.1016/s0040-4039(01)00842-5,2001-07-01,0.585130102153097
Tetrahedron,Total synthesis of marine diterpenoid stolonidiol,,10.1016/s0040-4039(01)02032-9,2001-12-01,0.585130102153097
Tetrahedron,A total synthesis of (+)-Castanospermine,,10.1016/s0040-4039(00)79888-1,1991-08-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-5-iminodaunomycinone and (±)-4-demethoxy-5-iminodaunomycinone,,10.1016/s0040-4039(00)74501-1,1991-02-01,0.585130102153097
Tetrahedron,First total synthesis of macrosphelides C and F,,10.1016/s0040-4039(01)00285-4,2001-04-01,0.585130102153097
Tetrahedron,Total synthesis of rubrolide M and some of its unnatural congeners,,10.1016/s0040-4039(02)00202-2,2002-03-01,0.585130102153097
Tetrahedron,Total synthesis of muconin,,10.1016/s0040-4039(02)02182-2,2002-11-01,0.585130102153097
Tetrahedron,"Total synthesis of tetronolide, the aglycon of tetrocarcins",,10.1016/s0040-4039(00)93498-1,1991-09-01,0.585130102153097
Tetrahedron,Total Synthesis of Herbimycin A,,10.1016/s0040-4039(00)79452-4,1991-10-01,0.585130102153097
Tetrahedron,A total synthesis of GPI anchor of trypanosoma brucei,,10.1016/s0040-4039(00)74856-8,1991-01-01,0.585130102153097
Tetrahedron,"Total synthesis of puerarin, an isoflavone C-glycoside",,10.1016/s0040-4039(03)01715-5,2003-09-01,0.585130102153097
Tetrahedron,A total synthesis of (±)-huperzine A,,10.1016/s0040-4039(01)93719-0,1989-01-01,0.585130102153097
Tetrahedron,Total synthesis of (−)-dactylyne and (−)-isodactylyne,,10.1016/s0040-4039(00)74257-2,1992-07-01,0.585130102153097
Tetrahedron,Total synthesis of marine diterpene fuscol,,10.1016/s0040-4039(00)77678-7,1992-01-01,0.585130102153097
Tetrahedron,An enantiospecific total synthesis of allosamizoline,,10.1016/s0040-4039(00)77717-3,1992-02-01,0.585130102153097
Tetrahedron,Total synthesis of dan shen diterpenoid quinones,,10.1016/s0040-4039(00)91882-3,1992-02-01,0.585130102153097
Tetrahedron,"Total synthesis of (11R, 12S)-diHETE",,10.1016/s0040-4039(00)74847-7,1991-01-01,0.585130102153097
Tetrahedron,Total synthesis of the amaryllidaceae alkaloid ungeremine,,10.1016/s0040-4039(00)71219-6,1991-01-01,0.585130102153097
Tetrahedron,Total synthesis of microcarpalide,,10.1016/s0040-4039(03)00441-6,2003-03-01,0.585130102153097
Tetrahedron,Total synthesis of (+)-crocacin A,,10.1016/s0040-4039(03)01171-7,2003-06-01,0.585130102153097
Tetrahedron,Total synthesis of (+)-laurallene,,10.1016/s0040-4039(03)00432-5,2003-03-26,0.585130102153097
Tetrahedron,The total synthesis of (−)-tetrahydrolipstatin,,10.1016/s0040-4039(03)00443-x,2003-03-01,0.585130102153097
Tetrahedron,Total synthesis of the muscarines,,10.1016/s0040-4039(00)80041-6,1988-01-01,0.585130102153097
Tetrahedron,A total synthesis of macrosphelides C and F from l-(+)-arabinose,,10.1016/j.tetlet.2003.09.034,2003-10-01,0.585130102153097
Tetrahedron,A formal total synthesis of aplysiatoxin,,10.1016/s0040-4039(00)93449-x,1991-09-01,0.585130102153097
Tetrahedron,Total synthesis of (+)-laurencin,,10.1016/s0040-4039(00)74256-0,1992-07-01,0.585130102153097
Tetrahedron,Total synthesis of the macrodiolide pyrenophorol,,10.1016/0040-4039(91)80368-g,1991-03-01,0.585130102153097
Tetrahedron,The first total synthesis of trichostatin D,,10.1016/j.tetlet.2004.11.004,2004-12-15,0.585130102153097
Tetrahedron,First total synthesis of (+)-viroallosecurinine,,10.1016/j.tetlet.2004.05.031,2004-06-01,0.585130102153097
Tetrahedron,Total synthesis of ginkgolide a,,10.1016/0040-4039(88)85122-0,1988-01-01,0.585130102153097
Tetrahedron,Total Synthesis of (±)-N-Acetylcolchinol,,10.1016/s0040-4039(00)80622-x,1988-01-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-trinoranastreptene,,10.1016/s0040-4039(00)80710-8,1988-01-01,0.585130102153097
Tetrahedron,Total synthesis of erbstatin.,,10.1016/s0040-4039(00)96084-2,1987-01-01,0.585130102153097
Tetrahedron,Total synthesis of the spiroketal macrolide (+) milbemycin α1,,10.1016/s0040-4039(00)60158-2,1993-11-01,0.585130102153097
Tetrahedron,"The total synthesis of argiotoxins 636, 659 and 673",,10.1016/s0040-4039(00)82310-2,1988-01-01,0.585130102153097
Tetrahedron,Total synthesis of dihydroteleocidin B-4 (dihydroteleocidin B),,10.1016/s0040-4039(00)82322-9,1988-01-01,0.585130102153097
Tetrahedron,First total synthesis of (−)-Verruculogen tr-2,,10.1016/s0040-4039(00)80288-9,1988-01-01,0.585130102153097
Tetrahedron,Total synthesis of bromobeckerelide,,10.1016/s0040-4039(00)72724-9,1989-01-01,0.585130102153097
Tetrahedron,Total synthesis of (+)-cylindricine C,,10.1016/j.tetlet.2004.05.142,2004-06-22,0.585130102153097
Tetrahedron,First total synthesis of valeriananoid A,,10.1016/s0040-4039(03)00064-9,2003-02-01,0.585130102153097
Tetrahedron,The Total synthesis of (+)-artemisinin and (+)-9-desmethyltemesinin,,10.1016/s0040-4039(00)96582-1,1987-01-01,0.585130102153097
Tetrahedron,Total synthesis of dehydroaltenusin,,10.1016/s0040-4039(03)00072-8,2003-02-01,0.585130102153097
Tetrahedron,Total synthesis of prodigiosin,,10.1016/s0040-4039(00)95451-0,1987-01-01,0.585130102153097
Tetrahedron,A formal total synthesis of geneserine,,10.1016/s0040-4039(01)91381-4,1987-01-01,0.585130102153097
Tetrahedron,The total synthesis of argiopine (argiotoxin-636),,10.1016/s0040-4039(00)96851-5,1987-01-01,0.585130102153097
Tetrahedron,Total synthesis of (+)-disparlure,,10.1016/s0040-4039(00)96165-3,1987-01-01,0.585130102153097
Tetrahedron,Total synthesis of punaglandin 4,,10.1016/s0040-4039(00)95721-6,1987-01-01,0.585130102153097
Tetrahedron,"The total synthesis of delesserine, leucodrin, and dilaspirolactone aglycone",,10.1016/s0040-4039(00)96146-x,1987-01-01,0.585130102153097
Tetrahedron,Total synthesis of psorospermin,,10.1016/j.tetlet.2004.12.006,2004-12-19,0.585130102153097
Tetrahedron,Enantiocontrolled total synthesis of (+)-bakkenolide-A,,10.1016/s0040-4039(00)80838-2,1988-01-01,0.585130102153097
Tetrahedron,Total synthesis of (−) verbenalol and (−) epiverbenalol,,10.1016/s0040-4039(00)80163-x,1988-01-01,0.585130102153097
Tetrahedron,Total synthesis of yuehchukene,,10.1016/0040-4039(88)85068-8,1988-01-01,0.585130102153097
Tetrahedron,Total synthesis of atroviridin,,10.1016/s0040-4039(03)00629-4,2003-04-01,0.585130102153097
Tetrahedron,Total synthesis of venustatriol,,10.1016/0040-4039(88)85113-x,1988-01-01,0.585130102153097
Tetrahedron,Total synthesis of (+)-thyrsiferol and (+)-venustatriol,,10.1016/s0040-4039(00)86672-1,1988-01-01,0.585130102153097
Tetrahedron,The first total synthesis of calabricoside A,,10.1016/s0040-4039(03)01706-4,2003-09-01,0.585130102153097
Tetrahedron,Total synthesis of (+)-decarestrictine L,,10.1016/s0040-4039(00)73848-2,1993-09-01,0.585130102153097
Tetrahedron,Total synthesis of pamamycin-607,,10.1016/s0040-4039(01)01665-3,2001-10-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-epimagnolin A,,10.1016/s0040-4039(00)01958-4,2001-01-01,0.585130102153097
Tetrahedron,A total synthesis of AI-77-B,,10.1016/s0040-4039(00)92088-4,1992-06-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-homopumiliotoxin 223G,,10.1016/s0040-4039(01)01389-2,2001-10-01,0.585130102153097
Tetrahedron,Total synthesis of (+)-crocacin C,,10.1016/s0040-4039(00)02002-5,2001-01-01,0.585130102153097
Tetrahedron,Total synthesis of luzopeptin C,,10.1016/s0040-4039(01)00080-6,2001-03-01,0.585130102153097
Tetrahedron,"Total synthesis of the prenylated cyclopeptide trunkamide A, a cytotoxic metabolite from Lissoclinum sp.",,10.1016/s0040-4039(01)00194-0,2001-03-01,0.585130102153097
Tetrahedron,Total synthesis of crotomachlin,,10.1016/s0040-4039(00)73888-3,1993-08-01,0.585130102153097
Tetrahedron,Total synthesis of myxovirescin A1,,10.1016/s0040-4039(00)77041-9,1994-07-01,0.585130102153097
Tetrahedron,Total synthesis of (−)-bistatramide C,,10.1016/s0040-4039(00)77148-6,1994-04-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-epibatidine,,10.1016/0040-4039(94)88492-7,1994-12-01,0.585130102153097
Tetrahedron,Total synthesis of arthrobacilin A,,10.1016/s0040-4039(00)76898-5,1994-05-01,0.585130102153097
Tetrahedron,First total synthesis of pseudodistomin tetrahydroacetate,,10.1016/0040-4039(92)88093-k,1992-07-01,0.585130102153097
Tetrahedron,"Total synthesis of nephritogenic glycopeptide, nephritogenoside",,10.1016/s0040-4039(00)74132-3,1992-01-01,0.585130102153097
Tetrahedron,Total synthesis of variolin B,,10.1016/s0040-4039(01)01881-0,2001-12-01,0.585130102153097
Tetrahedron,Total synthesis of luotonin A,,10.1016/s0040-4039(99)00349-4,1999-04-01,0.585130102153097
Tetrahedron,Total synthesis of (+)-pseudohygroline,,10.1016/j.tetlet.2010.01.060,2010-01-25,0.585130102153097
Tetrahedron,Total synthesis of (+)-aspergillide C,,10.1016/j.tetlet.2011.01.078,2011-01-24,0.585130102153097
Tetrahedron,Total synthesis of Resolvin E1,,10.1016/j.tetlet.2011.03.035,2011-04-12,0.585130102153097
Tetrahedron,Total synthesis of the antiinflammatory and proresolving protectin D1,,10.1016/j.tetlet.2011.03.152,2011-04-15,0.585130102153097
Tetrahedron,Total synthesis of (±)-dysibetaine CPa,,10.1016/j.tetlet.2011.06.034,2011-06-28,0.585130102153097
Tetrahedron,Total synthesis of topsentolide B2,,10.1016/j.tetlet.2011.02.014,2011-02-07,0.585130102153097
Tetrahedron,Total synthesis of (−)-cleistenolide,,10.1016/j.tetlet.2011.01.124,2011-02-02,0.585130102153097
Tetrahedron,Total synthesis of Hirtellanine A,,10.1016/j.tetlet.2010.03.092,2010-03-30,0.585130102153097
Tetrahedron,Total synthesis of myceliothermophins A–E,,10.1016/j.tetlet.2012.07.058,2012-07-20,0.585130102153097
Tetrahedron,"A stereocontrolled total synthesis of a ganglio-ganglioside GM1b, IV3NeuAcαGgOse4Cer",,10.1016/s0040-4039(00)94561-1,1990-01-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-monomorine,,10.1016/j.tetlet.2012.08.041,2012-08-16,0.585130102153097
Tetrahedron,Total synthesis of (–)-diversifolin,,10.1016/j.tetlet.2009.03.192,2009-04-03,0.585130102153097
Tetrahedron,The first total synthesis of (−)-bitungolide E,,10.1016/j.tetlet.2011.04.008,2011-04-15,0.585130102153097
Tetrahedron,Total synthesis of fluvirucinine A1,,10.1016/j.tetlet.2011.06.087,2011-06-30,0.585130102153097
Tetrahedron,Total synthesis of radicamine B and 5-epi-radicamine B,,10.1016/j.tetlet.2011.09.043,2011-09-22,0.585130102153097
Tetrahedron,First total synthesis of (+)-Carainterol A,,10.1016/j.tetlet.2010.02.001,2010-02-05,0.585130102153097
Tetrahedron,Stereocontrolled total synthesis of (±)-β-necrodol,,10.1016/s0040-4039(99)00737-6,1999-06-01,0.585130102153097
Tetrahedron,Total synthesis of (+)-4-deoxygigantecin,,10.1016/s0040-4039(97)00856-3,1997-06-01,0.585130102153097
Tetrahedron,First Total Synthesis of (+)-Secosyrin 1,,10.1016/s0040-4039(97)00380-8,1997-04-01,0.585130102153097
Tetrahedron,Enantiospecific total synthesis of tryprostatin A,,10.1016/s0040-4039(97)00077-4,1997-02-01,0.585130102153097
Tetrahedron,First total synthesis of (+)-heteroplexisolide E,,10.1016/j.tetlet.2012.04.065,2012-04-21,0.585130102153097
Tetrahedron,Total synthesis of the cytotoxic Annonaceous acetogenin (30S)-bullanin,,10.1016/s0040-4039(97)10739-0,1998-03-01,0.585130102153097
Tetrahedron,First total synthesis of fungerin an antifungal alkaloid from Fusarium sp.,,10.1016/s0040-4039(98)01203-9,1998-08-01,0.585130102153097
Tetrahedron,"First total synthesis of 1,2,3,4-tetrahydronaphtho[2,1-f]isoquinolines",,10.1016/s0040-4039(97)10737-7,1998-03-01,0.585130102153097
Tetrahedron,Total synthesis of an aglycone of spiramycin,,10.1016/s0040-4039(97)10758-4,1998-03-01,0.585130102153097
Tetrahedron,Total synthesis of 2-Arachidonylglycerol (2-Ara-Gl),,10.1016/s0040-4039(99)00028-3,1999-02-01,0.585130102153097
Tetrahedron,The first total synthesis of (±)-zenkequinone B,,10.1016/j.tetlet.2011.02.103,2011-04-19,0.585130102153097
Tetrahedron,Stereocontrolled total synthesis of Neuroprotectin D1/Protectin D1 and its aspirin-triggered stereoisomer,,10.1016/j.tetlet.2012.01.032,2012-01-14,0.585130102153097
Tetrahedron,Total synthesis of resolvin E2,,10.1016/j.tetlet.2010.01.109,2010-02-09,0.585130102153097
Tetrahedron,A formal total synthesis of (−)-brevisamide,,10.1016/j.tetlet.2010.11.013,2010-11-14,0.585130102153097
Tetrahedron,Total synthesis of (±)-hibiscone C,,10.1016/j.tetlet.2011.01.111,2011-02-02,0.585130102153097
Tetrahedron,"Total synthesis of maremycins A, B, C1/C2, D1, and D2",,10.1016/j.tetlet.2011.11.118,2011-12-06,0.585130102153097
Tetrahedron,Total synthesis of (−)-muricatacin,,10.1016/j.tetlet.2011.08.160,2011-09-07,0.585130102153097
Tetrahedron,Total synthesis of stagonolide B,,10.1016/j.tetlet.2011.12.119,2012-01-03,0.585130102153097
Tetrahedron,Total synthesis of (±)-isophellibiline,,10.1016/j.tetlet.2011.10.161,2011-11-07,0.585130102153097
Tetrahedron,Total synthesis of (±)-folicanthine,,10.1016/s0040-4039(01)90909-8,1963-01-01,0.585130102153097
Tetrahedron,Total synthesis of graphislactone G,,10.1016/j.tetlet.2010.04.024,2010-04-13,0.585130102153097
Tetrahedron,Total synthesis of argyrins A and E,,10.1016/j.tetlet.2011.03.021,2011-03-16,0.585130102153097
Tetrahedron,Total synthesis of (±)-Phosphonothrixin,,10.1016/s0040-4039(98)01403-8,1998-09-01,0.585130102153097
Tetrahedron,A total synthesis of (±)-hispanolone,,10.1016/s0040-4039(98)01408-7,1998-09-01,0.585130102153097
Tetrahedron,Total synthesis of diazaquinomycin A,,10.1016/s0040-4039(97)10589-5,1998-02-01,0.585130102153097
Tetrahedron,Total synthesis of (+)-aspermytin A,,10.1016/j.tetlet.2010.05.107,2010-05-28,0.585130102153097
Tetrahedron,First total synthesis of (±)-adunctin B,,10.1016/j.tetlet.2011.10.018,2011-10-16,0.585130102153097
Tetrahedron,Towards the total synthesis of clerodin. Part I.,,10.1016/s0040-4039(00)79435-4,1991-10-01,0.585130102153097
Tetrahedron,Total synthesis of bengamide E,,10.1016/s0040-4039(00)74488-1,1991-02-01,0.585130102153097
Tetrahedron,Formal total synthesis of grahamimycin A1,,10.1016/s0040-4039(00)79484-6,1991-01-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-galanolactone,,10.1016/s0040-4039(00)95251-1,1989-01-01,0.585130102153097
Tetrahedron,Total synthesis of marine alkaloids (±)-hapalindoles J and M,,10.1016/s0040-4039(00)99587-x,1989-01-01,0.585130102153097
Tetrahedron,Total synthesis of (+)-milbemycin β1,,10.1016/s0040-4039(00)99203-7,1989-01-01,0.585130102153097
Tetrahedron,Total synthesis of (−)-betaenone C,,10.1016/s0040-4039(01)80742-5,1989-01-01,0.585130102153097
Tetrahedron,A total synthesis of manzamine c,,10.1016/s0040-4039(01)89018-3,1989-01-01,0.585130102153097
Tetrahedron,First total synthesis of strobilurin B,,10.1016/s0040-4039(01)80582-7,1989-01-01,0.585130102153097
Tetrahedron,Total synthesis of (+)-altholactone,,10.1016/s0040-4039(01)93504-x,1989-01-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-stemodinone,,10.1016/s0040-4039(97)00173-1,1997-03-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-martinelline,,10.1016/s0040-4039(02)02331-6,2002-12-01,0.585130102153097
Tetrahedron,The first total synthesis of goniothalesdiol,,10.1016/s0040-4039(02)01599-x,2002-09-01,0.585130102153097
Tetrahedron,Total synthesis of myriocin,,10.1016/s0040-4039(02)02371-7,2002-12-01,0.585130102153097
Tetrahedron,First total synthesis of strongylodiol A,,10.1016/s0040-4039(02)00066-7,2002-02-01,0.585130102153097
Tetrahedron,The total synthesis of (±)-arisugacin A,,10.1016/s0040-4039(02)00551-8,2002-04-01,0.585130102153097
Tetrahedron,Total synthesis op (±) acetomycin,,10.1016/s0040-4039(00)92712-6,1991-07-01,0.585130102153097
Tetrahedron,Total synthesis of the elemanolides (±) zempoalin A and B,,10.1016/s0040-4039(01)80282-3,1989-01-01,0.585130102153097
Tetrahedron,Total synthesis of pyridomycin,,10.1016/s0040-4039(00)70713-1,1989-01-01,0.585130102153097
Tetrahedron,Total synthesis of (+)-Yingzhaosu A,,10.1016/s0040-4039(00)93555-x,1991-10-01,0.585130102153097
Tetrahedron,A stereocontrolled total synthesis of (±)-renieramycin A,,10.1016/s0040-4039(00)98010-9,1990-01-01,0.585130102153097
Tetrahedron,"Stereocontrolled total synthesis of (±)-ptaquilosin, the aglycone of ptaquiloside, a bracken carcinogen",,10.1016/s0040-4039(00)99630-8,1989-01-01,0.585130102153097
Tetrahedron,Total synthesis of rhizoxin D,,10.1016/s0040-4039(97)01605-5,1997-09-01,0.585130102153097
Tetrahedron,"Total synthesis of 1,3-dideoxynojirimycin",,10.1016/s0040-4039(97)10166-6,1997-11-01,0.585130102153097
Tetrahedron,Total synthesis of dolabradiene,,10.1016/s0040-4039(01)89505-8,1964-01-01,0.585130102153097
Tetrahedron,Total synthesis of marine diterpenoid kalihinene X,,10.1016/s0040-4039(02)00212-5,2002-03-01,0.585130102153097
Tetrahedron,Total synthesis of (±) pseudophrynamine A,,10.1016/s0040-4039(00)97926-7,1990-01-01,0.585130102153097
Tetrahedron,Total synthesis of (−)-acetomycin,,10.1016/0040-4039(90)80138-c,1990-01-01,0.585130102153097
Tetrahedron,Total synthesis of rifamycin W,,10.1016/0040-4039(90)80023-f,1990-01-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-pulo'upone,,10.1016/0040-4039(88)85201-8,1988-01-01,0.585130102153097
Tetrahedron,The total synthesis of (±)erigerol,,10.1016/s0040-4039(00)82378-3,1988-01-01,0.585130102153097
Tetrahedron,Total synthesis of (±) aspidofractinine,,10.1016/s0040-4039(00)99263-3,1989-01-01,0.585130102153097
Tetrahedron,Total synthesis of (+)- and (−)-norsecurinine,,10.1016/s0040-4039(01)93926-7,1989-01-01,0.585130102153097
Tetrahedron,"Total synthesis of sporochnols, fish deterrents from a marine alga",,10.1016/s0040-4039(02)00857-2,2002-05-01,0.585130102153097
Tetrahedron,Total synthesis of (−)-vallesamidine,,10.1016/s0040-4039(02)00256-3,2002-03-01,0.585130102153097
Tetrahedron,Total synthesis of () pseudophrynaminol,,10.1016/s0040-4039(00)94671-9,1990-01-01,0.585130102153097
Tetrahedron,Total synthesis of (+)-ptilocaulin,,10.1016/s0040-4039(00)97726-8,1990-01-01,0.585130102153097
Tetrahedron,Total synthesis of bengamide E,,10.1016/s0040-4039(02)00022-9,2002-02-01,0.585130102153097
Tetrahedron,Formal total synthesis of the trinorguaiane sesquiterpenes (+/−)-clavukerin A and (+/−)-isoclavukerin,,10.1016/s0040-4039(02)00402-1,2002-04-01,0.585130102153097
Tetrahedron,Total synthesis of (+)-crocacin D,,10.1016/s0040-4039(02)00289-7,2002-04-01,0.585130102153097
Tetrahedron,The first total synthesis of iPF4α-VI and its deuterated analog,,10.1016/s0040-4039(02)00398-2,2002-04-01,0.585130102153097
Tetrahedron,Total synthesis of cytotoxic sponge alkaloids hachijodines F and G,,10.1016/s0040-4039(02)00379-9,2002-04-01,0.585130102153097
Tetrahedron,First total synthesis of (±)-helibisabonol A,,10.1016/s0040-4039(02)01381-3,2002-09-01,0.585130102153097
Tetrahedron,A regiospecific total synthesis of ellipticine via nitrene insertion,,10.1016/s0040-4039(00)95184-0,1989-01-01,0.585130102153097
Tetrahedron,Total synthesis of (+)-citreoviral,,10.1016/s0040-4039(00)80191-4,1988-01-01,0.585130102153097
Tetrahedron,Total synthesis and stereochemical assignment of (±)-Epiderstatin,,10.1016/s0040-4039(00)74118-9,1992-01-01,0.585130102153097
Tetrahedron,Total synthesis of merodesmosine,,10.1016/j.tetlet.2022.154106,2022-08-26,0.585130102153097
Tetrahedron,Towards the total synthesis of metacridamides A and B,,10.1016/j.tetlet.2022.153640,2022-01-17,0.585130102153097
Tetrahedron,Total synthesis of (±)−paralemnolin A,,10.1016/j.tetlet.2024.154991,2024-03-06,0.585130102153097
Tetrahedron,Total synthesis of (±)-3-thiaglutamate,,10.1016/j.tetlet.2024.155246,2024-08-13,0.585130102153097
Tetrahedron,Total synthesis of clavulones,,10.1016/s0040-4039(00)89265-5,1985-01-01,0.585130102153097
Tetrahedron,Total synthesis of (±) stoechospermol,,10.1016/0040-4039(94)88217-7,1994-09-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-epicubenol,,10.1016/s0040-4039(00)73497-6,1994-07-01,0.585130102153097
Tetrahedron,The first total synthesis of (±)- pygmaeocin B,,10.1016/0040-4039(94)85070-4,1994-01-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-erythrodiene and (±)-spirojatamol,,10.1016/j.tetlet.2021.153291,2021-07-22,0.585130102153097
Tetrahedron,The total synthesis of (±)-cycloeudesmol,,10.1016/s0040-4039(00)61888-9,1985-01-01,0.585130102153097
Tetrahedron,First total synthesis of aspergillolide,,10.1016/j.tetlet.2022.154081,2022-08-17,0.585130102153097
Tetrahedron,Total synthesis of apramycin,,10.1016/s0040-4039(00)94028-0,1983-01-01,0.585130102153097
Tetrahedron,Total synthesis of phenolic alkaloids,,10.1016/s0040-4039(00)81924-3,1983-01-01,0.585130102153097
Tetrahedron,Total Synthesis of (±) isoclovene,,10.1016/s0040-4039(00)94169-8,1983-01-01,0.585130102153097
Tetrahedron,Total synthesis of marine prostanoids clavulones,,10.1016/s0040-4039(01)91091-3,1984-01-01,0.585130102153097
Tetrahedron,Total synthesis of colletodiol,,10.1016/s0040-4039(01)81188-6,1984-01-01,0.585130102153097
Tetrahedron,Total synthesis of asperlicin D,,10.1016/j.tetlet.2005.11.123,2005-12-16,0.585130102153097
Tetrahedron,Total synthesis of bioactive frustulosin and frustulosinol,,10.1016/j.tetlet.2005.11.150,2005-12-22,0.585130102153097
Tetrahedron,Total synthesis of (+)-kuhistaferone,,10.1016/j.tetlet.2004.12.129,2005-01-15,0.585130102153097
Tetrahedron,Total synthesis of applanatumols X and Y,,10.1016/j.tetlet.2020.152611,2020-11-04,0.585130102153097
Tetrahedron,Total synthesis of selaginellin A,,10.1016/j.tetlet.2021.153295,2021-07-27,0.585130102153097
Tetrahedron,Total synthesis of (+)-porothramycin B,,10.1016/s0040-4039(00)77629-5,1993-04-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-triptoquinone A,,10.1016/s0040-4039(00)60582-8,1993-01-01,0.585130102153097
Tetrahedron,A total synthesis of the pyrrolophenthridone alkaloid oxoassoanine,,10.1016/s0040-4039(00)73705-1,1993-09-01,0.585130102153097
Tetrahedron,A total synthesis of dragmacidin B,,10.1016/0040-4039(94)85056-9,1994-01-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-chaetoxanthone B,,10.1016/j.tetlet.2021.153390,2021-09-15,0.585130102153097
Tetrahedron,Total synthesis of halogenated spirocyclic polyketide (±)-actinospirol A,,10.1016/j.tetlet.2022.153975,2022-06-23,0.585130102153097
Tetrahedron,Total synthesis of (±)-applanatumol B,,10.1016/j.tetlet.2023.154584,2023-06-08,0.585130102153097
Tetrahedron,Total synthesis of matlystatin A,,10.1016/s0040-4039(00)61363-1,1993-01-01,0.585130102153097
Tetrahedron,Total synthesis of macrosphelides B and A,,10.1016/s0040-4039(99)02323-0,2000-03-01,0.585130102153097
Tetrahedron,Formal total synthesis of (+)-boronolide,,10.1016/s0040-4039(00)00749-8,2000-06-01,0.585130102153097
Tetrahedron,The first total synthesis of tetronasin (M139603),,10.1016/s0040-4039(00)60377-5,1993-03-01,0.585130102153097
Tetrahedron,Toward a total synthesis of stigmatellin; an unproductive C-1′–C-2′ disconnection,,10.1016/s0040-4039(00)00813-3,2000-07-01,0.585130102153097
Tetrahedron,"Total synthesis of lembehyne A, a neuritogenic spongean polyacetylene",,10.1016/s0040-4039(01)00038-7,2001-03-01,0.585130102153097
Tetrahedron,Total synthesis of restricticin,,10.1016/s0040-4039(00)61633-7,1993-01-01,0.585130102153097
Tetrahedron,A formal total synthesis of modhephene,,10.1016/s0040-4039(00)61421-1,1993-12-01,0.585130102153097
Tetrahedron,A total synthesis of the sesquiterpene quinone metachromin-A,,10.1016/s0040-4039(00)76220-4,1994-02-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-heliannuol A,,10.1016/0040-4039(94)85020-8,1994-09-01,0.585130102153097
Tetrahedron,Total synthesis of the marine sesquiterpene quinone (−)-cyclozonarone,,10.1016/s0040-4039(01)01748-8,2001-11-01,0.585130102153097
Tetrahedron,Total synthesis of 6-epi-sarsolilide A,,10.1016/s0040-4039(99)02126-7,2000-02-01,0.585130102153097
Tetrahedron,"The first total synthesis of the antitumor macrolide, rhizoxin",,10.1016/s0040-4039(00)77486-7,1993-02-01,0.585130102153097
Tetrahedron,Total synthesis of upial,,10.1016/s0040-4039(00)60329-5,1993-02-01,0.585130102153097
Tetrahedron,The total synthesis of chrysotricine,,10.1016/s0040-4039(00)00146-5,2000-03-01,0.585130102153097
Tetrahedron,First total synthesis of BE-12406 A,,10.1016/s0040-4039(00)60738-4,1994-06-01,0.585130102153097
Tetrahedron,A total synthesis of (±)-herbertene,,10.1016/s0040-4039(00)76905-x,1994-05-01,0.585130102153097
Tetrahedron,Total synthesis of anhydro levuglandin D2,,10.1016/s0040-4039(01)91219-5,1984-01-01,0.585130102153097
Tetrahedron,Total synthesis of ethisolide from“naked sugars”,,10.1016/0040-4039(94)88024-7,1994-02-01,0.585130102153097
Tetrahedron,"Total synthesis of chlorinated phenylpyrrole antibiotics, (+)- and (−)-neopyrrolomycins",,10.1016/s0040-4039(00)61354-0,1993-01-01,0.585130102153097
Tetrahedron,Total synthesis of the trisaccharide of olivomycin A,,10.1016/s0040-4039(00)73854-8,1993-09-01,0.585130102153097
Tetrahedron,Total synthesis of (−)-stemoamide,,10.1016/s0040-4039(00)78234-7,1994-08-01,0.585130102153097
Tetrahedron,Total synthesis of the polyene macrolide roxaticin,,10.1016/s0040-4039(00)78257-8,1994-08-01,0.585130102153097
Tetrahedron,The first total synthesis of mauritine-A,,10.1016/s0040-4039(00)01335-6,2000-09-01,0.585130102153097
Tetrahedron,The first total synthesis of (±)-grimaldone,,10.1016/s0040-4039(00)00136-2,2000-03-01,0.585130102153097
Tetrahedron,Total synthesis of angustine and angustoline,,10.1016/j.tetlet.2020.151757,2020-02-19,0.585130102153097
Tetrahedron,Total synthesis of Met10-teixobactin,,10.1016/j.tetlet.2019.06.027,2019-06-17,0.585130102153097
Tetrahedron,Total synthesis of anithiactins A-C and thiasporine A,,10.1016/j.tetlet.2019.01.038,2019-01-21,0.585130102153097
Tetrahedron,"First total synthesis of rhuscholide A, glabralide B and denudalide",,10.1016/j.tetlet.2019.151059,2019-08-17,0.585130102153097
Tetrahedron,Total synthesis of beauveriolide I,,10.1016/j.tetlet.2005.09.188,2005-10-15,0.585130102153097
Tetrahedron,A biomimetic total synthesis of (+)-intricarene,,10.1016/j.tetlet.2006.06.150,2006-08-07,0.585130102153097
Tetrahedron,A total synthesis of (±)-dihydropalustrine,,10.1016/s0040-4039(01)80263-x,1984-01-01,0.585130102153097
Tetrahedron,Total Synthesis of PI-091,,10.1016/00404-0399(50)1049n-,1995-07-31,0.585130102153097
Journal of the American Chemical Society,Total Synthesis of Mannopeptimycins .ALPHA. and .BETA.,,,2016-01-01,0.585130102153097
Tetrahedron,Total synthesis of (+)-tryptoquivaline,,10.1016/s0040-4039(01)91189-x,1984-01-01,0.585130102153097
Tetrahedron,Total synthesis of bicyclomycin,,10.1016/s0040-4039(00)94158-3,1983-01-01,0.585130102153097
Tetrahedron,First total synthesis of mueggelone,,10.1016/s0040-4039(00)01285-5,2000-11-01,0.585130102153097
Tetrahedron,Total synthesis of leontopodioside A,,10.1016/j.tetlet.2020.151886,2020-03-28,0.585130102153097
Tetrahedron,Total synthesis of remdesivir,,10.1016/j.tetlet.2021.153590,2021-12-09,0.585130102153097
Tetrahedron,Total synthesis of microansamycin I,,10.1016/j.tetlet.2021.152945,2021-02-23,0.585130102153097
Tetrahedron,Total synthesis of aspidophytine,,10.1016/j.tetlet.2006.08.115,2006-09-19,0.585130102153097
Tetrahedron,Total synthesis of (±)-pentenomycin,,10.1016/j.tetlet.2006.05.156,2006-06-13,0.585130102153097
Tetrahedron,Total synthesis of stevastelin B3,,10.1016/j.tetlet.2005.06.073,2005-07-02,0.585130102153097
Tetrahedron,Total synthesis of diaportheone A,,10.1016/j.tetlet.2018.11.055,2018-11-22,0.585130102153097
Tetrahedron,Total synthesis of granulodione,,10.1016/j.tetlet.2018.11.069,2018-11-28,0.585130102153097
Tetrahedron,Total synthesis of (+)-hanegokedial,,10.1016/s0040-4039(00)81792-x,1983-01-01,0.585130102153097
Tetrahedron,Total synthesis of Punicagranine,,10.1016/j.tetlet.2019.150989,2019-07-27,0.585130102153097
Tetrahedron,Total synthesis of (±)-parvifoline,,10.1016/s0040-4039(00)73502-7,1994-07-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-pterosin M and (±)-onitisin,,10.1016/j.tetlet.2023.154363,2023-01-20,0.585130102153097
Tetrahedron,Towards the total synthesis of aleurodiscal,,10.1016/j.tetlet.2023.154613,2023-06-12,0.585130102153097
Tetrahedron,Stereocontrolled total synthesis of isocomene sesquiterpenes,,10.1016/s0040-4039(01)81201-6,1984-01-01,0.585130102153097
Tetrahedron,Total synthesis of “(±)-senoxydene”,,10.1016/s0040-4039(01)80023-x,1984-01-01,0.585130102153097
Tetrahedron,Total synthesis of costatone: a monoterpene from the red seaweed: plocarnium costatum,,10.1016/s0040-4039(01)91104-9,1984-01-01,0.585130102153097
Tetrahedron,"Stereocontrolled total synthesis of (±)-lubiminol, a spirovetivane phytoalexin",,10.1016/s0040-4039(01)81379-4,1984-01-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-surugatoxin,,10.1016/s0040-4039(01)81451-9,1984-01-01,0.585130102153097
Tetrahedron,Total synthesis of lipoxin A4 and lipoxin B4 from butadiene,,10.1016/s0040-4039(99)02201-7,2000-02-01,0.585130102153097
Tetrahedron,Total synthesis of (+)-rolliniastatin 1,,10.1016/s0040-4039(00)77159-0,1994-04-01,0.585130102153097
Angewandte Chemie International Edition,Total Synthesis of Phorboxazole A,,10.1002/anie.200390322,2003-03-13,0.585130102153097
Angewandte Chemie International Edition,Total Synthesis of (+)-Pyrenolide D,,10.1002/1521-3773(20010316)40:6<1128::aid-anie11280>3.3.co;2-a,2001-03-16,0.585130102153097
Tetrahedron,Total synthesis of the alkaloid (−)-codonopsinine from l-xylose,,10.1016/j.tetlet.2005.02.140,2005-03-19,0.585130102153097
Tetrahedron,The total synthesis of (+)-payllanthostatin 2,,10.1016/s0040-4039(00)96788-1,1987-01-01,0.585130102153097
Tetrahedron,"The total synthesis of (±)-myo-inositol-1,3,4-trisphosphate, (±)-myo-inositol-2,4,5-trisphosphate and (±)-myo-inositol-1,3,4,5-tetrakisphosphate",,10.1016/s0040-4039(00)96548-1,1987-01-01,0.585130102153097
Tetrahedron,Cyclisation of allyl silanes. Formal total synthesis of (±)-mesembrine,,10.1016/s0040-4039(00)89298-9,1985-01-01,0.585130102153097
Tetrahedron,A formal total synthesis of dactylol,,10.1016/s0040-4039(01)80832-7,1985-01-01,0.585130102153097
Tetrahedron,Total synthesis of amauromine,,10.1016/s0040-4039(00)61945-7,1985-01-01,0.585130102153097
Tetrahedron,Total synthesis of α-yohimbine,,10.1016/s0040-4039(00)95001-9,1985-01-01,0.585130102153097
Tetrahedron,Total synthesis of (+)-castanospermine from D-mannose,,10.1016/s0040-4039(00)98767-7,1985-01-01,0.585130102153097
Tetrahedron,A total synthesis of methylenomycin B,,10.1016/s0040-4039(01)84608-6,1985-01-01,0.585130102153097
Tetrahedron,A formal total synthesis of (±)-aphidicolin,,10.1016/s0040-4039(00)95038-x,1985-01-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-atractylon and (±)-lindestrene,,10.1016/s0040-4039(01)84607-4,1985-01-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-sarcophytol-M,,10.1016/s0040-4039(00)73565-9,1993-04-01,0.585130102153097
Tetrahedron,Total synthesis of (±) Baiyunol,,10.1016/s0040-4039(00)84767-x,1986-01-01,0.585130102153097
Tetrahedron,Total synthesis of erbstatin,,10.1016/s0040-4039(00)85330-7,1986-01-01,0.585130102153097
Tetrahedron,Total synthesis of leukotriene (+)-LTB4 from D-mannitol1,,10.1016/s0040-4039(00)84936-9,1986-01-01,0.585130102153097
Tetrahedron,A formal total synthesis of aklavinone via a blocked anthraquinone tautomer,,10.1016/s0040-4039(00)84398-1,1986-01-01,0.585130102153097
Tetrahedron,Total synthesis of (-)-dihydrocelacinnine and (d-celabenzine,,10.1016/s0040-4039(00)83978-7,1986-01-01,0.585130102153097
Tetrahedron,A total synthesis of (±)-obscurinervidine,,10.1016/s0040-4039(00)98334-5,1985-01-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-pyrenolide B,,10.1016/s0040-4039(00)94790-7,1985-01-01,0.585130102153097
Tetrahedron,Total synthesis of fumitremorgin B,,10.1016/s0040-4039(00)85436-2,1986-01-01,0.585130102153097
Tetrahedron,Total synthesis of elaiophylin (azalomycin B),,10.1016/s0040-4039(00)85053-4,1986-01-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-isoavenaciolide and (±)-avenaciolide,,10.1016/s0040-4039(00)84792-9,1986-01-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-bisabolangelone,,10.1016/s0040-4039(00)85112-6,1986-01-01,0.585130102153097
Tetrahedron,Total synthesis of 4-Demethoxy-8-nordaunomycinone,,10.1016/s0040-4039(00)89110-8,1985-01-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-pseudopterosin A–F and K–L aglycone,,10.1016/j.tetlet.2004.01.060,2004-02-04,0.585130102153097
Tetrahedron,Stereochemical assignment of the fungal metabolite xestodecalactone A by total synthesis,,10.1016/j.tetlet.2004.02.005,2004-02-27,0.585130102153097
Tetrahedron,The first total synthesis of lymphostin,,10.1016/j.tetlet.2004.01.140,2004-02-21,0.585130102153097
Tetrahedron,Total synthesis of the marine cytotoxic caulibugulones A–D,,10.1016/j.tetlet.2004.06.007,2004-07-20,0.585130102153097
Tetrahedron,Total synthesis of nothapodytine B and (±)-mappicine,,10.1016/j.tetlet.2004.03.089,2004-04-13,0.585130102153097
Tetrahedron,Total synthesis of (+)-mikrolin,,10.1016/s0040-4039(00)96348-2,1987-01-01,0.585130102153097
Tetrahedron,A formal total synthesis of (±)-strigol,,10.1016/s0040-4039(00)96293-2,1987-01-01,0.585130102153097
Tetrahedron,Total synthesis of lyngbyatoxin A (teleocidin A-1) and teleocidin A-2,,10.1016/s0040-4039(00)96097-0,1987-01-01,0.585130102153097
Tetrahedron,Total synthesis of prolycopene,,10.1016/s0040-4039(00)96832-1,1987-01-01,0.585130102153097
Tetrahedron,A formal total synthesis of (-)-isoavenaciolide,,10.1016/s0040-4039(00)87895-8,1988-01-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-manzacidin D,,10.1016/j.tetlet.2004.08.038,2004-08-26,0.585130102153097
Tetrahedron,Total synthesis of the (+)-pheromone of the male swift moth L.,,10.1016/s0040-4039(00)84456-1,1986-01-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-arteannuin B,,10.1016/s0040-4039(00)84886-8,1986-01-01,0.585130102153097
Tetrahedron,Total synthesis of ulithiacyclamide,,10.1016/s0040-4039(00)84831-5,1986-01-01,0.585130102153097
Tetrahedron,Formal total synthesis of shikonin via Dötz benzannulation,,10.1016/j.tetlet.2004.05.018,2004-06-09,0.585130102153097
Tetrahedron,Total synthesis of dipiperamide A and revision of stereochemical assignment,,10.1016/j.tetlet.2004.11.042,2004-12-10,0.585130102153097
Tetrahedron,Total synthesis of (±)-cocculolidine,,10.1016/s0040-4039(01)01650-1,2001-11-01,0.585130102153097
Tetrahedron,The first total synthesis of (+)-rogioloxepane A,,10.1016/s0040-4039(00)02281-4,2001-02-01,0.585130102153097
Tetrahedron,Total synthesis of sphingofungin E,,10.1016/s0040-4039(01)00246-5,2001-04-01,0.585130102153097
Tetrahedron,Total synthesis of epothilone A,,10.1016/s0040-4039(01)01585-4,2001-10-01,0.585130102153097
Tetrahedron,Total synthesis of epibatidine,,10.1016/s0040-4039(00)73674-4,1993-05-01,0.585130102153097
Tetrahedron,The total synthesis of piptosidin,,10.1016/s0040-4039(00)96756-x,1987-01-01,0.585130102153097
Tetrahedron,Total synthesis of monoterpenoid isoquinoline alkaloids,,10.1016/0040-4039(84)80026-x,1984-01-01,0.585130102153097
Tetrahedron,Total synthesis of (+)-dihydromevinolin,,10.1016/s0040-4039(01)91076-7,1984-01-01,0.585130102153097
Tetrahedron,Total synthesis of tanshinone IIA,,10.1016/j.tetlet.2020.152102,2020-06-04,0.585130102153097
Tetrahedron,Total synthesis of enhygrolide A and analogs,,10.1016/j.tetlet.2020.151786,2020-02-29,0.585130102153097
Tetrahedron,Total synthesis of inubosin B,,10.1016/j.tetlet.2020.152641,2020-11-16,0.585130102153097
Tetrahedron,Total synthesis of hirsutellide A,,10.1016/j.tetlet.2005.04.087,2005-05-24,0.585130102153097
Tetrahedron,"Enantiospecific total synthesis of phytoalexins, (+)-solanascone, (+)-dehydrosolanascone, and (+)-anhydro-β-rotunol",,10.1016/j.tetlet.2005.08.124,2005-09-15,0.585130102153097
Tetrahedron,Total synthesis of didmolamides A and B,,10.1016/j.tetlet.2005.02.097,2005-03-11,0.585130102153097
Tetrahedron,Total synthesis of neosurugatoxin,,10.1016/s0040-4039(00)85175-8,1986-01-01,0.585130102153097
Tetrahedron,Total synthesis of africanol,,10.1016/s0040-4039(00)84524-4,1986-01-01,0.585130102153097
Tetrahedron,Total synthesis of (±) podophyllotoxin,,10.1016/s0040-4039(00)95770-8,1987-01-01,0.585130102153097
Journal of Organic Chemistry,Stereocontrolled total synthesis of leukotriene B4,International audience,10.1021/jo00028a046,1992-01-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-cyclooroidin,,10.1016/j.tetlet.2005.10.060,2005-11-03,0.585130102153097
Tetrahedron,Total synthesis of manoalide and seco-manoalide,,10.1016/s0040-4039(00)98937-8,1985-01-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-podophyllotoxin and (±)-epipodophyllotoxin.,,10.1016/s0040-4039(00)89274-6,1985-01-01,0.585130102153097
Tetrahedron,Total synthesis of (±)-alliacolide,,10.1016/s0040-4039(00)98750-1,1985-01-01,0.585130102153097
Tetrahedron,A total synthesis of (±)-cannabisativine,,10.1016/s0040-4039(00)98972-x,1985-01-01,0.585130102153097
Tetrahedron,A total synthesis of ()-anhydrocannabisativine.,,10.1016/s0040-4039(00)98971-8,1985-01-01,0.585130102153097
Tetrahedron,"First regiospecific, enantiospecific total synthesis of gardnerine and gardnutine",,10.1016/j.tetlet.2005.04.051,2005-05-06,0.585130102153097
Tetrahedron,Total synthesis of (−)-incarvilline,,10.1016/j.tetlet.2005.01.173,2005-02-21,0.585130102153097
Tetrahedron,Total synthesis of (−)-microcarpalide from d-mannitol,,10.1016/j.tetlet.2005.06.070,2005-07-06,0.585130102153097
Tetrahedron,Total synthesis of (±)-sumatranin C,,10.1016/j.tetlet.2025.155561,2025-04-02,0.585130102153097
Tetrahedron,Total synthesis of (±)-sanadaol,,10.1016/s0040-4039(00)96035-0,1987-01-01,0.585130102153097
Tetrahedron,"Total synthesis of (3S,4S,2′S)- and (3R,4R,2′S)-viridiofungin A triester",,10.1016/j.tetlet.2004.07.086,2004-08-11,0.585130102153097
Tetrahedron,Stereocontrolled total synthesis of (±)-pisiferol and (±)-pisiferal,,10.1016/j.tetlet.2004.10.089,2004-11-09,0.585130102153097
Tetrahedron,Total synthesis of (+)-eldanolide from -ribonolactone,,10.1016/s0040-4039(00)84573-6,1986-01-01,0.585130102153097
Tetrahedron,The total synthesis of (±)-α-costal,,10.1016/s0040-4039(00)94966-9,1985-01-01,0.585130102153097
Tetrahedron,Total synthesis of manoalide,,10.1016/s0040-4039(00)84996-5,1986-01-01,0.585130102153097
Tetrahedron,The total synthesis of allamandin,,10.1016/s0040-4039(00)94743-9,1985-01-01,0.585130102153097
Tetrahedron,Total synthesis of kadsurenone and its analogs,,10.1016/s0040-4039(00)84004-6,1986-01-01,0.585130102153097
Tetrahedron,Total synthesis of fumitremorgin B,,10.1016/s0040-4039(00)87809-0,1986-01-01,0.585130102153097
Tetrahedron,Total synthesis of d-(+)-biotin,,10.1016/j.tetlet.2004.08.019,2004-08-21,0.585130102153097
Tetrahedron,"A total synthesis of d,1-histrionicotoxin",,10.1016/s0040-4039(00)98253-4,1985-01-01,0.585130102153097
Tetrahedron,Total synthesis of (-)-ilicicolin H,,10.1016/j.tetlet.2024.155095,2024-05-03,0.585130102153097
Tetrahedron,Total synthesis of terfestatins a and B,,10.1016/j.tetlet.2020.151891,2020-04-01,0.585130102153097
Tetrahedron,Total synthesis of selaginellin S,,10.1016/j.tetlet.2020.152031,2020-05-11,0.585130102153097
Tetrahedron,Corrigendum to “Total synthesis of (+)-petromyroxol” [Tetrahedron Lett. 56 (2015) 3933–3935],,10.1016/j.tetlet.2019.151420,2019-11-25,0.585130102153097
Tetrahedron,A total synthesis of (+)-brazilin,,10.1016/j.tetlet.2020.152052,2020-05-18,0.585130102153097
Tetrahedron,Total synthesis of (±)-cannabisativine,,10.1016/s0040-4039(01)80076-9,1984-01-01,0.585130102153097
Tetrahedron,First total synthesis of acronyculatin S,,10.1016/j.tetlet.2025.155868,2025-10-21,0.585130102153097
Tetrahedron,"Total synthesis of jadomycins A, B, and l-digitoxosyl-phenanthroviridin",,10.1016/j.tetlet.2022.153919,2022-06-03,0.585130102153097
Tetrahedron,Total synthesis of sinopyrine B,,10.1016/j.tetlet.2022.154072,2022-08-06,0.585130102153097
Tetrahedron,The total synthesis of eupomatilones 2 and 5,,10.1016/j.tetlet.2005.08.140,2005-09-15,0.585130102153097
Tetrahedron,First total synthesis of (−)-diospongin B,,10.1016/j.tetlet.2005.10.129,2005-11-11,0.585130102153097
Tetrahedron,A total synthesis of spiruchostatin A,,10.1016/j.tetlet.2005.12.031,2005-12-29,0.585130102153097
Journal of Organic Chemistry,Total Synthesis of (+)-Superstolide A,"A convergent and highly stereocontrolled total synthesis of the cytotoxic macrolide (+)-superstolide A is described. Key features of this synthesis include the use of bimetallic linchpin 36b for uniting the C(1)-C(15) (43) and the C(20)-C(27) (38) fragments of the natural product, a late-stage Suzuki macrocyclization of 49, and a highly diastereoselective transannular Diels-Alder reaction of macrocyclic octaene 4. In contrast, the intramolecular Diels-Alder reaction of pentaenal 5 provided the desired cycloadduct with lower stereoselectivity (6:1:1).",10.1021/jo801794s,2008-10-29,0.5851151334592014
Tetrahedron,One-pot two step synthesis of 5-cyano-dihydropyrimidinones using polyphosphate ester,,10.1016/j.tetlet.2008.02.162,2008-03-05,0.5851141522750101
Journal of the American Chemical Society,Calyciphylline B-Type Alkaloids: Total Syntheses of (−)-Daphlongamine H and (−)-Isodaphlongamine H,"The first total synthesis of the complex hexacylic Daphniphyllum alkaloid (-)-daphlongamine H has been accomplished. Key to the success of the strategy are a complexity-building Mannich reaction, efficient cyclizations, and a highly diastereoselective hydrogenation to assemble multigram quantities of the tricyclic core bearing four contiguous stereocenters. Following construction of the hydro-indene substructure by means of a Pauson-Khand reaction, endgame redox manipulations delivered the natural product. Importantly, the synthetic studies have also given access to (-)-isodaphlongamine H and led to a revision of the reported structure of deoxyisocalyciphylline B.",10.1021/jacs.9b03576,2019-05-10,0.5851101686657021
Journal of Organic Chemistry,Asymmetric Synthesis of Enantioenriched (+)-Elaeokanine A,"The key transformation in the total synthesis of (+)-elaeokanine A was accomplished by asymmetric deprotonation of N-Boc pyrrolidine, followed by the reaction of the in situ generated enantioenriched stereogenic cuprate reagent with (E)-4-bromo-1-iodo-1-trimethylsilyl-1-butene with retention of configuration. N-Boc deprotection, followed by a one-pot olefin isomerization and intramolecular amine alkylation afforded a bicyclic vinyl bromide that was converted into (+)-elaeokanine A by sequential halogen metal exchange and reaction of the organolithium reagent with N-butanoylmorpholine.",10.1021/jo060717q,2006-06-23,0.5851092806811273
Tetrahedron,Synthetic applications of umpoled vilsmeier reagents — A new simple one-pot route to isatins from formanilides,,10.1016/s0040-4039(97)82969-3,1996-12-01,0.5851059800616158
Tetrahedron,"Synthetic studies on mitomycins. 2. A synthesis of 9a-hydroxy-5,8-dideoxomitosane skeleton through a novel retroaldol type of ring-opening reaction.",,10.1016/s0040-4039(01)86342-5,1979-01-01,0.5851035123369729
Tetrahedron,"Total synthesis of (−)-hemiasterlin, a structurally novel tripeptide that exhibits potent cytotoxic activity",,10.1016/s0040-4039(96)02335-0,1997-01-01,0.5850940754119374
Organic Letters,"Determination by Enantioselective Synthesis of the Absolute Configuration of CPE, a Potential Intermediate in Coronatine Biosynthesis","The first enantioselective synthesis of the methyl ester of CPE, a potential intermediate in coronatine (COR) biosynthesis, is described. Comparison of the specific rotation of the synthetic ester with that of the methyl ester of natural CPE established that the latter possesses the (R) configuration. This configuration is the same as that found at the corresponding asymmetric center of coronatine. Structure: see text.",10.1021/ol0165037,2001-08-29,0.5850851253763927
Synlett,"An IMDA Approach to Tigliane and Daphnane Diterpenoids: Generation of Rings A, B and C Incorporating C-18","A synthesis of the tricyclic ring system of the daphnane and tigliane diterpenes, incorporating C-18 and the C-13 oxygen functionality found in phorbol and related compounds is described. The convergent synthesis utilizes an intramolecular Diels-Alder reaction as the key stereocontrolling step.",10.1055/s-2002-22700,2002-01-01,0.5850761151727961
Organic Letters,Total Synthesis of Clavepictines A and B and Pictamine,"[Structure: see text] A short route for assembling clavepictines A and B and pictamine is described, which features elaboration of its trisubstituted piperidine moiety via condensation of a beta-keto sulfone with an l-alanine-derived bromide and subsequent alkylative cyclization and construction of its quinolizidine skeleton via a diastereoselective intramolecular conjugate addition. The possible stereochemical course for this conjugate addition is discussed.",10.1021/ol060960b,2006-06-21,0.5850746934811969
Organic Letters,Regio- and Stereoselective Synthesis of Multisubstituted Olefins and Conjugate Dienes by Using α-Oxo Ketene Dithioacetals as the Building Blocks,"An efficient palladium(0)-catalyzed, Cu(I)-mediated synthetic route to trisubstituted olefins and conjugate dienes has been developed via oxo directing Liebeskind-Srogl cross-coupling reactions of gem-dihaloolefin-type α-oxo ketene dithioacetals with aryl and alkenylboronic acids. The synthetic protocol has demonstrated rare examples of transition-metal-promoted transformations of ketene dithioacetals, providing a novel route to highly functionalized conjugate dienes.",10.1021/ol201620g,2011-07-15,0.5850687593178651
Tetrahedron,Ring isomerization of isoflavone glycosides. Synthesis of tectoridin-4′-methyl ether and other flavone glucosides.,,10.1016/s0040-4039(00)71085-9,1965-01-01,0.5850685604368199
Synlett,"Preparation of 3-Alkyl-Oxindoles by Copper(II)-Mediated C-H, Ar-H Coupling Followed by Decarboxyalkylation",A novel route for the conversion of anilides into 3-alkyl-oxindoles is described in which a copper(II)-mediated cyclization process is followed by an acid-mediated decarboxyalkylation. Scope and limitation studies are reported together with a telescoped variant which incorporates in situ N-deprotection.,10.1055/s-0029-1219392,2010-02-18,0.5850597016858018
Tetrahedron,"The synthesis and chemistry of functionalized furochromones.4.1 Addition of nitronate anions to 30bromochromone and 6-bromofurochromone. An expedient route to furo(3′,2′:6,7)-benzopyrano(2,3-d)-isoxazolones and chromono(2,3-d)isoxazolones.",,10.1016/s0040-4039(00)91842-2,1992-02-01,0.5850575429994582
Tetrahedron,A novel approach for the one-pot synthesis of linear and angular fused quinazolinones,,10.1016/j.tetlet.2011.04.019,2011-04-15,0.5850573934943981
Synlett,Short and Efficient Large Scale Synthesis of (<i>R</i>)-2-Benzylsuccinic Acid 4-[4-(BOC-amino)-1-piperidide] Monoamide: N-Terminal Component of Renin Inhibitors by Asymmetric Hydrogenation,All articles of this category An economical asymmetric four step synthesis of a 2(R)-benzylsuccinic acid-4-monoamide for use as an N-terminal component in renin inhibitors has been developed (Scheme 3).,10.1055/s-1993-22387,1993-01-01,0.5850562437261716
Synlett,Synthesis of New 3-[(Alkylthio)methyl]-1-hydroxy-2-phenylindoles,"The syntheses of new 3-[(alkylthio)methyl]-1-hydroxy-2-phenylindoles are presented. The substrates, obtained by efficient three-step synthesis, were treated with various thiol nucleophiles in the presence of SnCl2·2H2O to provide target compounds, through the consecutive processes of reduction, condensation, and addition in one pot. The mechanistic studies on reaction pathways and the involved intermediates are described.",10.1055/s-0034-1380275,2015-03-12,0.5850558567592846
European Journal of Organic Chemistry,A High‐Yielding Synthesis of EIDD‐2801 from Uridine**,"A simple reordering of the reaction sequence allowed the improved synthesis of EIDD-2801, an antiviral drug with promising activity against the SARS-CoV-2 virus, starting from uridine. Compared to the original route, the yield was enhanced from 17 % to 61 %, and fewer isolation/purification steps were needed. In addition, a continuous flow procedure for the final acetonide deprotection was developed, which proved to be favorable toward selectivity and reproducibility.",10.1002/ejoc.202001340,2020-11-12,0.5850547067746814
Journal of Organic Chemistry,Efficient Synthesis of [<sup>3</sup>H]-Sanglifehrin A via Selective Oxidation/Reduction of Alcohols at C<sub>31</sub> and C<sub>35</sub>,"[Reaction: see text]. Sanglifehrin A is a novel complex natural product showing strong immunosuppressive activity and remarkably high affinity for cyclophilin A. To assess its pharmacokinetic properties in vivo, an efficient synthetic route was developed to introduce a tritium label in position C35 of sangliferin A via an oxidation/reduction strategy. The synthetic approach is particularly attractive, because the C35-oxo intermediate 7 is available in good yield on large scale and the reducing agent, lithium tri-sec-butylborotritide, is readily available. An attempt to apply a similar strategy to the alcohol in position C31 led primarily to C31-epi-hydroxy sanglifehrin A under a variety of conditions.",10.1021/jo051112h,2005-10-14,0.5850543117690206
Synlett,"Practical and Novel One-Pot Protocol for the Synthesis of Highly Functionalized Pyridinols and Pyrido[1,2-a]-Fused 1,3-Diazaheterocycles","A novel and efficient protocol for the generation of substituted pyridinols and pyrido[1,2-a]-fused 1,3-diazaheterocycles from primary amine or 1,n-diamine, nitro ketene dithioacetal [1,l-bis(methylthio)-2-nitroethene] and dibenzylideneacetone as starting materials in a one-pot process combining a Michael addition ­reaction and nucleophilic addition under mild condition in high yield has been developed.",10.1055/s-0030-1259942,2011-04-07,0.585054168384405
Organic Process Research & Development,Large-Scale Tandem Cyclization Applied to Potentially High-Volume SSTR4 Agonists,"Somatostatin receptor subtype 4 (SSTR4) antagonists are potential clinical targets for pain. We describe the efforts toward a robust large-scale synthesis of certain small-molecule SSTR4 agonist compounds. Previous routes used metal-mediated reactions and produced stereochemical mixtures. The molecule has a 3-azabicyclo[3.1.0]hexane ring system with cis- stereochemistry. A unique tandem cyclization at the multi-kilogram scale was employed to generate the fused ring system with exclusive cis- stereochemistry observed. The potential commercial synthesis is an efficient, economical process with good control points. This novel tandem cyclization was implemented to swiftly scale up a similar compound for early-phase studies.",10.1021/acs.oprd.4c00144,2024-05-29,0.5850461447458739
Tetrahedron,Enantioselective synthesis of cyclopentane derivatives using zirconium-catalyzed asymmetric cyclization,,10.1016/s0040-4039(99)00472-4,1999-04-01,0.5850458243681277
Tetrahedron,A novel approach toward the synthesis of strigolactones through intramolecular [2+2] cycloaddition of ketenes and ketene-iminiums to olefins. Application to the asymmetric synthesis of GR-24,,10.1016/j.tetlet.2012.06.013,2012-06-12,0.5850410490641794
Synlett,Efficient Synthesis of Naturally Occurring Ligustilide,"All articles of this category Synthesis of naturally occurring ligustilide ( 1 ) was accomplished by the cyclization of alkynoic acid ( 9 ), which was prepared from acetal ( 3 ) in several steps, catalyzed by silver iodide or silver in mild reaction condition as key step. ligustilide - cyclization - silver catalyst - alkynoic acid",10.1055/s-1995-5102,1995-08-01,0.5850344052901383
Tetrahedron,A novel synthesis of methyl 5-substituted thiazole-4-carboxylates using 3-bromo-2-isocyanoacrylates (BICA),,10.1016/0040-4039(94)02186-f,1995-01-01,0.5850309922514099
Tetrahedron,A new route to branched-chain sugars by application of the nitromethane method to ketoses,,10.1016/s0040-4039(01)88500-2,1969-01-01,0.5850275039671485
Tetrahedron,Toward the total synthesis of tetrodotoxin: stereoselective construction of the 7-oxanorbornane intermediate,,10.1016/j.tetlet.2014.09.036,2014-09-16,0.5850270200147699
Journal of Organic Chemistry,Synthetic Approach Toward the Total Synthesis of Kempane Diterpenes via Transannular Diels−Alder Strategy,Total syntheses of two new (+/-)-kempane derivatives 30 and 47 were achieved with transannular Diels-Alder reaction (TADA) serving as the key step for the stereoselective formation of tricyclic [6.6.5] system 3. This synthetic approach also reveals that the geometry of the C3 group of such a tricyclic system plays an important role for the formation of the seven-membered kempane skeleton.,10.1021/jo061230k,2006-08-19,0.5850270084250434
Tetrahedron,Synthesis of 2-cyclopentadienylidene-2h-thiapyran by novel reductive rearrangement of a 6-thienylfulvene,,10.1016/0040-4039(91)80816-o,1991-07-01,0.5850262631383325
Journal of Organic Chemistry,"Divergent Synthesis of Bioactive Resorcinols Isolated from the Fruiting Bodies of <i>Hericium erinaceum</i>: Total Syntheses of Hericenones A, B, and I, Hericenols B–D, and Erinacerins A and B","Total syntheses of 5'- and 7'-oxidized geranyl resorcylates isolated from the fruiting bodies of Hericium erinaceum and the submerged cultures of a Stereum species were achieved. Our synthesis features derivatization of a suitably functionalized 5'-oxidized geranyl phthalide as a common intermediate, which was obtained by Stille coupling between the phthalide core and the side chain, into a series of natural products by divergent functional group manipulations. The crucial C5'-oxygen functionality was installed at the initial stage by alkylation by an α-cyano ethoxyethyl ether. From a common synthetic intermediate, eight total syntheses including hericenones A, B, and I, hericenols B-D, and erinacerins A and B were achieved (hericenol B and erinacerin B were synthesized as racemates). The structure of hericenone B established in the isolation paper was unambiguously revised as the carbonyl regioisomer at the lactam moiety.",10.1021/jo500795z,2014-05-15,0.5850243017361091
European Journal of Organic Chemistry,Improved Synthesis of D‐Isoglutamine: Rapid Access to Desmuramyl Analogues of Muramyl Dipeptide for the Activation of Intracellular NOD2 Receptor and Vaccine Adjuvant Applications,"Abstract Muramyl dipeptide (MDP) – the smallest immunomodulatory unit of bacterial peptidoglycan – has adjuvant activity and triggers the innate immune system against bacterial and viral infections. The inherited drawbacks of MDP, such as pyrogenicity and poor macrophage penetration, can be resolved by structural modifications, thereby improving its pharmacological profile and adjuvant activity. Herein, several desmuramyl analogues of MDP were designed by replacing the carbohydrate fragment (MurNAc) of the parent molecule with an immunomodulatory xanthine scaffold. The L−D configurations of the pharmacophoric dipeptidyl moiety were conserved and alkyl chains of moderate length were introduced at isoglutamine to enhance their cellular uptake. The synthesis of these analogues features a novel synthetic route for D‐isoglutamine fragment with an overall yield of &gt;50 % in ten to eleven steps. This sufficiently flexible approach provides rapid access to desmuramyl analogues of MDP on a gram scale, which can help accelerate the development of novel NOD2 agonists and immunoadjuvants.",10.1002/ejoc.202101170,2021-11-26,0.5850196640425144
Organic Letters,Exploring Chemical Diversity of Epoxyquinoid Natural Products:  Synthesis and Biological Activity of (−)-Jesterone and Related Molecules,"Enantioselective syntheses of the potent antifungal agent (-)-jesterone, its hydroxy epimer, and a dimeric quinone epoxide derivative are reported. The synthesis involves diastereoselective epoxidation of a chiral quinone monoketal derivative and regio- and stereoselective reduction of a quinone epoxide intermediate.",10.1021/ol0159367,2001-05-01,0.585019422797381
Tetrahedron,The cyperone route to agarofurans: stereoselective introduction of an hydroxy group at C-4,,10.1016/s0040-4039(02)00309-x,2002-04-01,0.5850145905516899
Organic Letters,Synthesis of Amphidinolide E C10−C26 Fragment,"The key C10-C26 fragment in a total synthesis of (-)-amphidinolide E has been prepared from an oxolane-containing C10-C17 segment (9, derived from L-glutamic acid) via a Julia-Kocienski reaction with aldehyde 3, followed by a Sharpless AD to obtain the desired diol. The C22-C26 fragment was installed by means of an efficient Suzuki-Molander coupling, with an organotrifluoroborate reagent (4, arising from a cross-metathesis reaction between a vinylboronate and 2-methyl-1,4-pentadiene).",10.1021/ol801923y,2008-10-07,0.5850119684304692
European Journal of Organic Chemistry,"Stereoselective Synthesis of Fluorinated Isoxazolidines and 2,3-Dihydroisoxazoles: A Cycloadditive Route to Enantiomerically Pure Amino Fluoro Alcohols",,10.1002/(sici)1099-0690(199907)1999:7<1665::aid-ejoc1665>3.3.co;2-4,1999-07-01,0.5850085805867941
Tetrahedron,Asymmetric synthesis of 2-chloroaziridines via a diastereoselective nucleophilic dichloromethylation and N-alkylation in one pot,,10.1016/j.tetlet.2018.07.056,2018-07-25,0.5850085561959318
Organic Letters,"Convergent, Stereoselective Synthesis of the GHIJ Fragment of Brevetoxin A","[reaction: see text] A stereoselective synthesis of the GHIJ fragment of brevetoxin A utilizing a convergent assembly strategy is described. Glycolate alkylation, ring-closing metathesis, and Hosomi-Sakurai reactions were central operations in the construction of the G ring and J ring subunits, which were united through a Horner-Wadsworth-Emmons coupling. Subsequent dehydrative cyclization produced an endocyclic enol ether that was further elaborated to the tetracyclic GHIJ fragment of brevetoxin A.",10.1021/ol0526625,2005-12-06,0.5850080664306386
Tetrahedron,An efficient synthesis of highly functionalized chiral lactams,,10.1016/j.tetlet.2011.07.021,2011-07-23,0.5850067483245743
Tetrahedron,An efficient unprecedented synthesis of novel functionalized imidazoles from secondary amino-N-carbothioic acid (phenyl-p-tolylimino-methyl)amides and dimethyl acetylenedicarboxylate,,10.1016/j.tetlet.2004.09.119,2004-10-21,0.5850058328477882
Tetrahedron,A strategy for the asymmetric synthesis of medium ring oxygen heterocycles: Enantioselective total synthesis of (+)-octahydrodeacetyldebromolaurencin,,10.1016/s0040-4039(00)80490-6,1988-01-01,0.5850039034373714
Organic Process Research & Development,Asymmetric Synthesis of LFA-1 Inhibitor BIRT2584 on Metric Ton Scale,"The synthesis of LFA-1 inhibitor BIRT2584 on metric-ton scale was accomplished by means of a safe and robust process. Highlights of the process include the asymmetric synthesis of the key advanced intermediate by implementation of Seebach’s self-regeneration of stereocenters principle, and a Ph 3 PCl 2 -induced dehydration of a critical urea followed by a regioselective bromination to give the elaborated 1 H -imidazo[1,2- a ]imidazol-2-one. A sulfonyl chloride intermediate was produced through Br/Mg exchange of iodoimidazole followed by addition to SO 2 in THF and subsequent oxidation. In a one-pot operation, the sulfonyl chloride was directly reacted with l -alaninamide using NaOH as base in aqueous DMF/THF to give BIRT2584.",10.1021/op200175t,2011-08-03,0.5849979173151238
Organic Letters,New Strategy for the Synthesis of Tetrahydroisoquinoline Alkaloids,"[reaction: see text] A general strategy for the formation of 1,3-cis-substituted tetrahydroisoquinolines is described from ortho-iodo imines involving Larock isoquinoline synthesis, addition of organolithium compounds to unactivated isoquinolines, and ionic hydrogenation. In addition, a new synthesis of lactams via an unprecedented azide cyclization in the presence of a sulfonium ion is described.",10.1021/ol034683+,2003-05-21,0.5849970300690059
European Journal of Organic Chemistry,On the Halogenation of Tyrosine <i>N</i>‐Oxime Methyl Ester,"Abstract Efficient syntheses of mono‐, di‐, and heterodihalogenated derivatives of tyrosine N ‐oxime methyl ester are reported. Monohalogenation with N ‐bromosuccinimide (NBS), N ‐chlorosuccinimide (NCS) or N ‐iodosuccinimide (NIS) was optimized by addition of acid to suppress dihalogenation, affording bromo, chloro, and iodo derivatives in 71 %, 50–53 %, and 78–80 % yields, respectively. Homodihalogenation utilized a two‐step, one‐flask process via a spirocyclic intermediate, yielding dibromo, dichloro, and diiodo analogues, respectively (75–76 %, 54–56 %, 79–80 %). This strategy was extended to synthesize hetero‐dihalogenated bromochloro, bromoiodo, and chloroiodo derivatives from monohalogenated analogues (50–77 %). Key to this approach was the formation of an oxidized spirocyclic intermediate using excess N ‐halosuccinimide, followed by Na₂S₂O₄ reduction. This method ensures complete conversion and simplifies purification. Nine halogenated building blocks were prepared. These methods provide practical access to versatile precursors for natural product synthesis and derivatization, offering potential for diverse synthetic applications including regioselective palladium‐catalyzed couplings.",10.1002/ejoc.202401153,2024-11-18,0.5849899665801541
Synthesis,Synthesis of the Tricyclic Core of the Marine Natural Product Labiatin A,"A synthetic route to a model of the tricyclic core of labiatin A is described. Two catalytic metal carbenoid reactions, C-H insertion and oxonium ylide generation with subsequent [2,3]-sigmatropic rearrangement, have been used to assemble the tricyclic system in an efficient and stereoselective manner.",10.1055/s-2005-918485,2005-01-01,0.5849896065534881
European Journal of Organic Chemistry,A New and Productive Route to 1‐Heteroarylcyclopropanols,"Abstract ( E / Z )‐2‐(1‐Allyloxycyclopropyl)‐3‐methoxyacrylonitrile ( 4 ‐All) was designed and prepared in five steps (58% overall yield) from ethyl cyclopropylidenacetate as a valuable precursor to various 1‐heteroarylcyclopropanols. Its condensation with amidines, guanidine, hydrazine, and methyl thioglycolate and subsequent removal of the allyl protecting group yields 1‐heteroarylcyclopropanols such as 1 ‐OH (36% over 2 steps), a very potent NO‐independent stimulator of soluble guanylate cyclase. Direct cleavage of the allyl ether protecting group [by palladium‐catalyzed substitution with lithium p ‐toluenesulfinate in AcOH or treatment with c ‐HexMgBr/Ti(O i Pr) 4 ] gives highly functionalized, sterically congested 1‐heteroarylcyclopropanols 29 , 30 , and 34 with intact amino and ester groups. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2003)",10.1002/ejoc.200390093,2003-01-15,0.5849884513469933
European Journal of Organic Chemistry,"Synthesis of 3,4,5‐Trisubstituted Isoxazoles via the ANRORC Rearrangement",A facile and versatile procedure for the synthesis of new functionalized derivatives of 3‐benzyl‐5‐(2‐hydroxyphenyl) isoxazole‐4‐carbaldehyde oxime has been described. The key step in the synthesis involves the ANRORC reaction of in‐situ generated 3‐(phenylethynyl)‐4H‐chromen‐4‐one with NH 2 OH · HCl.,10.1002/ejoc.202001103,2020-10-20,0.5849870298905863
Tetrahedron,A new synthesis of the anti-AIDS drug AZT from 5-methyluridine,,10.1016/0040-4039(95)01753-5,1995-10-01,0.5849788532272956
Tetrahedron,"A novel synthesis of tricyclo[5.3.1.01,5]undecanes: Total syntheses of 2-norCedrene and a funebrene analogue",,10.1016/s0040-4039(97)01168-4,1997-07-01,0.5849781736617684
Organic Letters,First Total Synthesis of Mosin B,"[figure: see text] The first total synthesis of mosin B and a diastereomer was accomplished using asymmetric desymmetrization of the sigma-symmetric diol and the Nozaki-Hiyama-Kishi reaction as the key steps. The THF core segment was stereoselectively constructed employing a stereodivergent synthesis starting from a common intermediate, 4-cyclohexene-1,2-diol, based on a desymmetrization strategy. By virtue of these synthetic results, it is suggested that the absolute configuration is 1a.",10.1021/ol006938e,2001-01-12,0.5849774139468719
Synlett,Novel Synthesis of Chiral Allenyl Sulfoxides and Their Potential Use in Asymmetric Reactions,"All articles of this category Chiral allenyl sulfoxides 4 are prepared by substitution of allenyllithiums on (-)-( S )-menthyl p -tolylsulfinate ( 1 ). The reactions are performed at -115 °C by an inverse addition procedure. Their use in the asymmetric synthesis of 4,4-dialkyl-1- tert -butyl(or phenyl)-2-( p -toluenesulfinyl)-2, 3-butadien-1-ols 7 is described.",10.1055/s-1992-21389,1992-01-01,0.584977352186129
Tetrahedron,Synthetic 6-glucosyl phospholipid as a drug transport system,,10.1016/s0040-4039(00)95541-2,1987-01-01,0.5849768468849152
Chemical Science,Bioinspired enantioselective synthesis of crinine-type alkaloids via iridium-catalyzed asymmetric hydrogenation of enones,"A bioinspired enantioselective synthesis of crinine-type alkaloids has been developed by iridium-catalyzed asymmetric hydrogenation of racemic cycloenones. The method features a biomimetic stereodivergent resolution of the substrates bearing a remote arylated quaternary stereocenter. Using this protocol, 24 crinine-type alkaloids and 8 analogues were synthesized in a concise and rapid way with high yield and high enantioselectivity.",10.1039/c7sc02112g,2017-01-01,0.5849767067413321
Organic Letters,Synthesis of the C-1−C-28 ABCD Unit of Spongistatin 1,The synthesis of the C-1-C-28 ABCD fragment of spongistatin is described. Anti-selective boron-mediated aldol coupling of a CD spiroketal ketone fragment to an AB spiroketal aldehyde unit forms the desired C1-C28 advanced intermediate. Other features include the double conjugate addition of a dithiol to an ynone to generate the key beta-keto-dithiane unit required for the synthesis of the AB spiroketal fragment. [reaction: see text],10.1021/ol035849+,2003-11-11,0.584975749477978
Organic Process Research & Development,Process Development for A Novel Pleuromutilin-Derived Antibiotic,"A scalable synthesis of a novel pleuromutilin-based antibiotic is reported. The synthesis features the scale-up of an interesting skeletal rearrangement of the pleuromutilin core and isolation of a highly purified product despite starting with relatively impure pleuromutilin. The use of Design of Experiment (DoE) and Principal Component Analysis (PCA) tools to achieve these goals is also discussed. Furthermore, the novel coupling of a carbamate and N -acyl-imidazole to produce the imidodicarbonate portion of the target molecule is described.",10.1021/op900104g,2009-07-02,0.5849724544638008
Organic Letters,"Nonplanar Aromatic Compounds. 6. [2]Paracyclo[2](2,7)pyrenophane. A Novel Strained Cyclophane and a First Step on the Road to a “Vögtle” Belt",A benzene ring nestled into the concave face of a bent pyrene characterizes the title compound in the crystal. The synthesis of this compound was accomplished using the valence isomerization−dehydrogenation (VID) method and marks the official launch of our journey en route to aromatic belts first proposed by Prof. Vögtle.,10.1021/ol016053i,2001-05-25,0.5849719302252684
Organic Process Research & Development,"A Practical and Robust Process to Produce SB-214857, Lotrafiban, ((2<i>S</i>)-7-(4,4<sup>‘</sup>-Bipiperidinylcarbonyl)-2,3,4,5-tetrahydro-4-methyl-3-oxo-1<i>H</i>-1, 4-Benzodiazepine-2-acetic Acid) Utilising an Enzymic Resolution as the Final Step","During the scale-up of a chemical process to produce phase II supplies of the chiral compound Lotrafiban, partial racemisation occurred to produce drug substance of unacceptable chiral purity. A new route capable of producing several hundred kilograms of Lotrafiban of high chiral purity had to be rapidly identified and scaled up. The strategy adopted was to employ an enzymic resolution as the final step, thus introducing the chirality under very mild conditions to prevent any racemisation. This was achieved using an immobilised form of the Candida antarctica B lipase in water at 30 °C. The biotransformation was demonstrated to be a robust, reliable, and an economic way to introduce the chirality into the Lotrafiban molecule.",10.1021/op025508w,2002-06-11,0.5849707419026435
Synthesis,Facile Synthesis of Polysubstituted 2-Pyrones via TfOH-Mediated Ring Expansion of 2-Acylcyclopropane-1-carboxylates,"Abstract A facile route to polysubstituted 2-pyrones from readily available 2-acylcyclopropane-1-aryl-1-carboxylates mediated by TfOH is reported. The strongly donating 1-aryl group is important for directing the C–C bond cleavage of the donor-acceptor cyclopropane ring, which then leads to the formation of the 2-pyrone ring through lactonization.",10.1055/a-1526-7839,2021-06-10,0.5849685176643781
Organic Letters,Total Synthesis of Jatrophane Diterpenes from <i>Euphorbia characias</i>,"The enantioselective total synthesis of the jatrophane diterpene (-)-15-O-acetyl-3-O-propionylcharaciol is described. Starting from an advanced cyclopentane building block, a B-alkyl Suzuki-Miyaura cross-coupling and carbonyl addition were utilized to assemble a fully functionalized triene, and a ring-closing metathesis was then employed to construct the rigid 12-membered ring. Twenty-five years after the original report on the isolation of the natural product, our total synthesis unambiguously corroborates the original tentative structural assignment.",10.1021/ol900819u,2009-05-19,0.5849674578541594
Journal of the American Chemical Society,Total Synthesis and Anti-Hepatitis C Virus Activity of MA026,"The first total synthesis of MA026 and the identification of its candidate target protein for anti-hepatitis C virus activity are presented. MA026, a novel lipocyclodepsipeptide isolated from the fermentation broth of Pseudomonas sp. RtIB026, consists of a cyclodepsipeptide, a chain peptide, and an N-terminal (R)-3-hydroxydecanoic acid. The first subunit, side chain 2, was prepared by coupling fatty acid moiety 4 with tripeptide 5. The key macrocyclization of the decadepsipeptide at L-Leu(10)-D-Gln(11) provided the second subunit, cyclodepsipeptide 3. Late-stage condensation of the two key subunits and final deprotection afforded MA026. This convergent, flexible, solution-phase synthesis will be invaluable in generating MA026 derivatives for future structure-activity relationship studies. An infectious hepatitis C virus (HCV) cell culture assay revealed that MA026 suppresses HCV infection into host hepatocytes by inhibiting the entry process in a dose-dependent manner. Phage display screening followed by surface plasmon resonance (SPR) binding analyses identified claudin-1, an HCV entry receptor, as a candidate target protein of MA026.",10.1021/ja410145x,2013-11-20,0.5849650888815895
Organic Process Research & Development,Process Development of the BACE Inhibitors BI 1147560 BS and BI 1181181 MZ,"The development of large-scale syntheses of two beta-site amyloid precursor protein cleaving enzyme (BACE) inhibitors is described. New methodologies were discovered to overcome safety and scalability problems with existing procedures. The sterically hindered quaternary, neopentyl stereocenter was formed in high diastereoselectivity by the addition of a carbamoyl anion to an N -sulfinyl ketimine. An aryl nitrile was installed by a palladium- and cyanide-free electrophilic cyanation affected by transnitrilation of an arylmagnesium derivative with dimethylmalononitrile. A safe route to an oxetanylmethylamine side chain was devised based on diethyl malonate and dibenzylamine starting materials. A mild enamine fluorination was developed for the synthesis of a fluoroisobutylamine side chain.",10.1021/acs.oprd.2c00325,2022-12-08,0.5849646536870288
Synlett,"Highly Diastereoselective 1,3-Dipolar Cycloaddition of a d-Galactose-Derived Nitrone with Dimethyl Maleate: Synthesis of Polyhydroxylated Perhydroazaazulenes","An intermolecular 1,3-dipolar cycloaddition of a d-­galactose-derived nitrone with dimethyl maleate was found to be perfectly diastereoselective at the nitrone carbon to give exclusive formation of isoxazolidine. The N-O bond reductive cleavage in isoxazolidine followed by lactam reduction afforded a pyrrolidine ring skeleton with sugar appendage that on acetonide cleavage and reductive amino-cyclization gave hitherto unknown hydroxy­methyl-substituted hexa- and pentahydroxy perhydroazaazulenes.",10.1055/s-0029-1217541,2009-07-01,0.584963482960855
Tetrahedron,"Diterpenoid total synthesis, an A→B→C approach. IV. Total synthesis of methyl -dehydroabietate",,10.1016/s0040-4039(00)90838-4,1967-01-01,0.5849629035387041
Organic Letters,"Diversity Oriented Convergent Access for Collective Total Synthesis of Bioactive Multifunctional Carbazole Alkaloids: Synthesis of Carbazomycin A, Carbazomycin B, Hyellazole, Chlorohyellazole, and Clausenaline D","Facile syntheses of imperative carbazole alkaloids carbazomycin A, carbazomycin B, hyellazole, chlorohyellazole, and clausenaline D have been demonstrated starting from readily available Boc-protected 3-formylindole and dimethyl maleate. The suitably substituted aromatic rings have been designed comprising three/four significant C-C bond forming reactions. The competent Wittig reaction, selective monoalkylations, one-pot regioselective Weinreb amide formation and Boc-deprotection, well designed Grignard reactions, dehydrative intramolecular cyclizations, and Baeyer-Villiger rearrangement of aromatic aldehydes were the main features.",10.1021/ol502721r,2014-10-09,0.5849604330315915
Organic Letters,"Total Synthesis of Natural (+)-(2‘<i>S</i>,3‘<i>R</i>)-Zoapatanol","[reaction: see text] (+)-Zoapatanol was synthesized by using four key-steps: a Suzuki cross-coupling to prepare a (Z)-alpha,beta-unsaturated ester followed by an enantioselective dihydroxylation to control the C2' and C3' stereocenters, an intramolecular Horner-Wadsworth-Emmons olefination to construct the oxepane ring, and a chemoselective nucleophilic addition/Birch reduction process of a Weinreb amide to introduce simultaneously the beta,gamma-unsaturated ketone on the side-chain and regenerate alcohols from benzyl ethers.",10.1021/ol049433n,2004-05-25,0.5849568808907957
Tetrahedron,"Enhancing the yield and diastereoselectivity of the Pictet-Spengler reaction: A highly efficient route to Cis-1,3-disubstituted tetrahydro-β-carbolines",,10.1016/s0040-4039(00)73247-3,1994-05-01,0.5849544802392782
Journal of Organic Chemistry,Azomethine Ylide Cycloaddition/Reductive Heterocyclization Approach to Oxindole Alkaloids:  Asymmetric Synthesis of (−)-Horsfiline,"The intermolecular [3 + 2] annulation of azomethine ylides with 2(2-nitrophenyl)acrylate dienophiles followed by reductive heterocyclization affords the spiro(indole-pyrrolidine) ring system. Hence, this enable us to accomplish a concise and highly enantioselective synthesis of (-)-horsfiline 1, based on chiral auxiliary-directed pi-face discrimination in the 1,3-dipolar cycloaddition of (1S,2R)-2-phenyl-1-cyclohexyl ester 4f with N-methylazomethine ylide.",10.1021/jo015854w,2001-11-17,0.5849516253184253
Journal of Organic Chemistry,Suzuki Cross-Coupling/Reductive Debenzyloxycarbonylation Sequence for the Syntheses of [<i>c</i>]Annulated Isoquinolines: Application for the Syntheses of Pancratistatin-like Isoquinolines,A two-step strategy involving Suzuki cross-coupling of boronic acids with a diverse array of alpha-iodoenones followed by hydrogenation is developed for the construction of [c]annulated isoquinolines. This mild and efficient procedure is also applied to the synthesis of highly oxygenated isoquinolines.,10.1021/jo801761f,2008-09-23,0.5849510617068965
Organic Letters,Efficient Stereoselective Synthesis of Novel Steroid−Polyquinane Hybrids,"A synthesis of steroid-polyquinane hybrids, a new class of molecular entities, is described. [reaction: see text]",10.1021/ol0342960,2003-05-29,0.5849506874039291
Synthesis,"Efficient Methods for the Synthesis of Thieno[3,2-b]thiophene and Thieno[3,2-b]furan Derivatives","A novel approach to the synthesis of thieno[3,2-b]thiophenes and thieno[3,2-b]furans bearing various substituents from readily accessible starting materials has been developed. The methodology is based on C- and O-alkylation of ethyl 4-hydroxy-2-methylthiophene-3-carboxylate with α-halo ketones, followed by cyclization.",10.1055/s-0029-1217019,2009-09-23,0.5849400337529521
Synthesis,Synthesis of 7-Arylpurines from Substituted Pyrimidines,"Abstract A simple three-step approach for the synthesis of substituted N7-arylpurines with an overall yield of the whole sequence from 40% to 71% is described. N7-Arylpurines were constructed by de novo synthesis from commercially available substituted 4-chloropyrimidine-5-amines. Different substituents at purine C2 and C6 were obtained by changing the corresponding substituents of the starting pyrimidine. Further, heteroaromatic, electron-deficient, and electron-rich aromatic groups were attached to the exocyclic amino group by iodane reagents under copper catalysis. This moiety is prepared to become purine N7 position after the ring closure. Finally, purine C8 substitution was varied during the last step of the developed sequence by employing different reagents for the purine ring closing reactions or post functionalization.",10.1055/a-1898-9675,2022-07-13,0.5849369252581351
Journal of Organic Chemistry,Synthetic Access to All Four Stereoisomers of Oxetin,"A short synthesis of all four stereoisomers of 3-amino-2-oxetanecarboxylic acid (oxetin) is described. The oxetane core is built using a Paternò-Büchi photochemical [2 + 2] cycloaddition; from the key intermediates, complementary resolution protocols provide access to enantiomerically pure oxetin and epi-oxetin on gram-scale.",10.1021/acs.joc.6b01795,2016-09-23,0.5849324756587535
Tetrahedron,"Synthesis and easy aromatisation of 5-substituted 6-(alkylthio)-2-methoxy-2,3-dihydropyridines. A new approach to the pyridine ring",,10.1016/s0040-4039(02)02423-1,2002-12-01,0.5849320735592316
Chemical Science,A new post-synthetic route to graft amino groups in porous organic polymers for CO <sub>2</sub> capture,"Herein, we report the development of a post-synthetic modification approach to introduce a high loading of formyl groups onto porous aromatic framework (PAF)-5 via Friedel–Crafts alkylation followed by hydrolysis.",10.1039/d5sc00355e,2025-01-01,0.5849247215655491
Angewandte Chemie International Edition,Design and Synthesis of TY‐Phos and Application in Palladium‐Catalyzed Enantioselective Fluoroarylation of<i>gem</i>‐Difluoroalkenes,"The first example of highly enantioselective fluoroarylation of gem-difluoroalkenes with aryl halides is presented by using a new chiral sulfinamide phosphine (Sadphos) type ligand TY-Phos. N-Me-TY-Phos can be easily synthesized on a gram scale from readily available starting materials in three steps. Salient features of this work including readily available starting materials, good yields, high enantioselectivities as well as broad substrate scope make this approach very practical and attractive. Notably, the asymmetric synthesis of an analogue of a biologically active molecule is also reported.",10.1002/anie.202008262,2020-09-25,0.58491882868958
Journal of Organic Chemistry,Taxane Synthesis through Intramolecular Pinacol Coupling at C-1−C-2. Construction and Oxidative Transformations of a C-Aromatic Taxane Diene,"A ten-linear-step construction of C-aromatic taxane diene 14 from ethyl isopropyl ketone, acryloyl chloride, and commercially available 8 is reported. This sequence concludes with an intramolecular pinacol coupling carried out on 13 . 14 is oxidized by m -chloroperbenzoic acid and dimethyldioxirane to give 17 through intermediate epoxide 20 and by VO(acac) 2 − t- BuOOH and Mo(CO) 6 − t- BuOOH to give 13 . 17 is converted efficiently into 22 upon treatment with Mo(CO) 6 − t- BuOOH, apparently through an unusual equilibration with isomeric 20, which is converted irreversibly to 22 . While these oxidative transformations highlight some of the peculiar reactivity patterns characteristic of taxane-related structures, the formation of 14 through an intramolecular pinacol coupling that joins C-1 and C-2 demonstrates the potential of this strategy for stereoselectively delivering advanced taxane synthesis intermediates.",10.1021/jo951935e,1996-01-01,0.584915661271992
Organic Letters,Synthetic Studies on Maitotoxin. 3. Stereoselective Synthesis of the BCDE-Ring System,The stereoselective synthesis of the BCDE-ring system of maitotoxin has been accomplished through a two-directional strategy for the construction of polycyclic ether. The key reactions involve SmI 2-induced double cyclization of a beta-alkoxyacrylate and a double dihydroxylation for construction of the B- and E-rings.,10.1021/ol8002699,2008-04-08,0.5849132357346394
European Journal of Organic Chemistry,Regioselective and Scalable Total Synthesis of Licochalcone C and Related Licoagrochalcones,"Abstract A novel efficient method for the synthesis of licochalcone C in good yield on up to 30 g scale was developed. The reaction sequence included relied on the directed ortho ‐metalation (DOM) of bis‐ O ‐MOM‐protected resorcinol for the regioselective C ‐prenylation, followed by metalation‐formylation, selective O ‐deprotection of a hydroxyl group located between the formyl and prenyl groups, its methylation, and aldol reaction with p ‐hydroxyacetophenone. Synthesis of structurally related retrochalcones, i.e., licoagrochalcones B, C, and D, was also proposed.",10.1002/ejoc.202201226,2022-12-09,0.5849081366189792
Journal of Organic Chemistry,Total Synthesis of Methyl Protodioscin:  A Potent Agent with Antitumor Activity,"Methyl protodioscin (1), otherwise known as 3-O-[alpha-L-rhamnopyranosyl-(1-->2)-[alpha-L-rhamnopyranosyl-(1-->4)]-beta-d-glucopyranosyl]-26-O-[beta-D-glucopyranosyl]-22-methoxy-25(R)-furost-5-ene-3 beta,26-diol, has been synthesized for the first time from diosgenin through nine steps in an overall yield of 7.8%.",10.1021/jo020683w,2003-04-05,0.5848989356465991
Journal of the American Chemical Society,Total Syntheses of Epothilones A and B,"Convergent, stereocontrolled total syntheses of the microtubule-stabilizing macrolides epothilones A ( 2 ) and B ( 3 ) have been achieved. Four distinct ring-forming strategies were pursued (see Scheme 1). Of these four, three were reduced to practice. In one approach, the action of a base on a substance possessing an acetate ester and a nonenolizable aldehyde brought about a remarkably effective macroaldolization see ( 89 → 90 + 91; 99 → 100 + 101 ), simultaneously creating the C2−C3 bond and the hydroxyl-bearing stereocenter at C-3. Alternatively, the 16-membered macrolide of the epothilones could be fashioned through a C12−C13 ring-closing olefin metathesis (e.g. see 111 → 90 + 117; 122 → 105 + 123 ) and through macrolactonization of the appropriate hydroxy acid (e.g. see 88 → 93 ). The application of a stereospecific B -alkyl Suzuki coupling strategy permitted the establishment of a cis C12−C13 olefin, thus setting the stage for an eventual site- and diastereoselective epoxidation reaction (see 96 → 2; 106 → 3 ). The development of a novel cyclopropane solvolysis strategy for incorporating the geminal methyl groups of the epothilones (see 39 → 40 → 41 ), and the use of Lewis acid catalyzed diene−aldehyde cyclocondensation (LACDAC) (see 35 + 36 → 37 ) and asymmetric allylation (see 10 → 76 ) methodology are also noteworthy.",10.1021/ja971946k,1997-10-01,0.584896128721063
Journal of Organic Chemistry,Direct Total Syntheses of Frenolicin B and Kalafungin via Highly Regioselective Diels-Alder Reactions,"Frenolicin B, an anticoccidial agent, has been synthesized in six steps from ketone 3. Racemic kalafungin, an antifungal agent, has been synthesized in five steps. The key step in both syntheses, a regioselective Diels-Alder reaction, proceeds with complete regiocontrol and in excellent yield. One rationale for the remarkable stereocontrol is that the lactone ring induces ring-puckering in the quinone subunit which, in consort with electrostatic repulsion, contributes to the regioselectivity.",10.1021/jo00110a017,1995-03-01,0.5848847555704582
Organic Letters,"Unified Total Syntheses of (±)-Sessilifoliamides B, C, and D","alkaloids sessilifoliamides B and D and the second synthesis of sessilifoliamide C have been completed from a simple pyrrole substrate. The bicyclic lactam core was prepared on a gram scale via a Brønsted acid mediated cyclization and controlled oxidation with Dess-Martin periodinane. This delivered sessilifoliamide C (and its C-11 epimer) in 24% yield over 11 steps, and sessilifoliamides B and D in 13 and 17 steps, respectively.",10.1021/acs.orglett.1c00895,2021-04-13,0.5848847133579583
Organic Letters,Enantioselective Synthesis of SB-203207,"Total synthesis of SB-203207 (1) was achieved, beginning with a desymmetrical C-H insertion reaction of a diazoester bearing our recently developed chiral auxiliary. Utilizing the optically active bicyclo[3.3.0]octane ring, four stereogenic centers were efficiently constructed in sequence. Finally, mild oxidation of 27 to carboxylic acid via a cyanohydrin intermediate and hydrolysis of cyanide to carboxyamide in the presence of the labile enamide group completed an efficient total synthesis of 1.",10.1021/ol5002973,2014-03-06,0.5848811342920676
Organic Letters,A Total Synthesis of (±)-<i>trans</i>-Kumausyne,A short total synthesis of (+/-)-trans-kumausyne is reported. Key steps include a tandem ring-opening-ring-closing metathesis and the effective introduction of the pentenyl side chain by allylation-cross metathesis. [reaction: see text],10.1021/ol051199t,2005-07-13,0.5848797550878819
Tetrahedron,Synthetic studies on teleocidin IV. An efficient synthesis of (-)-indolactam V,,10.1016/s0040-4039(00)85313-7,1986-01-01,0.5848761471818259
Tetrahedron,A new method for hydroxymethylene peptide isostere synthesis: Asymmetric synthesis of statine,,10.1016/s0040-4039(00)78545-5,1994-12-01,0.58487484038037
Journal of the American Chemical Society,Total Synthesis of (−)-Voacinol and (−)-Voacandimine C,"We describe the first total synthesis of complex aspidosperma alkaloids (-)-voacinol and (-)-voacandimine C via a late-stage C7-methylenation strategy inspired by a biogenetic hypothesis. We envisioned rapid access to these natural alkaloids from a common, symmetrical precursor assembled by methylenation of a D-ring-oxidized variant of the structurally related natural product (-)-deoxoapodine. Chemoselective N9-oxidation of a pentacyclic deoxoapodine precursor enabled the synthesis of the corresponding hexacyclic C8-aminonitrile. Stereocontrolled methylenation of a C8-enamine derivative of deoxoapodine, accessed by ionization of the C8-aminonitrile, afforded a symmetrical dodecacyclic bisaminonitrile as a versatile precursor to these bisindole alkaloids. The final-stage, biosynthesis-inspired, controlled reductive opening of the oxolane substructures of this dodecacyclic intermediate provided a unified approach to (-)-voacinol and (-)-voacandimine C, while direct reduction of the same intermediate afforded the structurally related (-)-methylenebisdeoxoapodine.",10.1021/jacs.2c03057,2022-05-11,0.5848730885349148
Journal of Organic Chemistry,The Double Reduction of Cyclic Sulfonamides for the Synthesis of (4<i>S</i>-Phenylpyrrolidin-2<i>R</i>-yl)methanol and 2<i>S</i>-Methyl-4<i>S</i>-phenylpyrrolidine,"The synthesis of (4S-phenylpyrrolidin-2R-yl)methanol and 2S-methyl-4S-phenylpyrrolidine has been achieved via the double reduction of their cyclic sulfonamide precursors which themselves were prepared following the stereoselective intramolecular Heck reaction of a chiral pool derived 2,5-dihydropyrrole. We have recently described a process whereby cyclic aryl sulfonamides, such as 2, are reductively ring-opened to furnish amino products in which the aryl group is incorporated in the final compound. (Evans, P.; McCabe, T.; Morgan, B. S.; Reau, S. Org. Lett. 2005, 7, 43.) The precursors for this reaction were assembled using an intramolecular Heck reaction followed by reduction of the alkene. Overall, this sequence represents an efficient means to construct molecules of this type in which the aryl sulfonyl moiety acts as both an N-protecting group and as an aryl donor. Use of Benkeser's stronger reducing conditions enables molecules such as 4 to be prepared in which both the sulfonamide functional group and the aromaticity of the aryl substituent have been destroyed.",10.1021/jo062189o,2007-01-26,0.5848658745531883
Tetrahedron,Toward a general synthesis of A-ring trihydroxylated vitamin D analogs: Synthesis of an A-ring synthon of ED-71 from d-arabinose,,10.1016/0040-4039(95)02008-d,1995-12-01,0.5848611530753214
Journal of Organic Chemistry,Evolution of a Strategy for the Enantioselective Total Synthesis of (+)-Psiguadial B,"(+)-Psiguadial B is a diformyl phloroglucinol meroterpenoid that exhibits antiproliferative activity against the HepG2 human hepatoma cancer cell line. This full account details the evolution of a strategy that culminated in the first enantioselective total synthesis of (+)-psiguadial B. A key feature of the synthesis is the construction of the trans-cyclobutane motif by a Wolff rearrangement with in situ catalytic, asymmetric trapping of the ketene. An investigation of the substrate scope of this method to prepare enantioenriched 8-aminoquinolinamides is disclosed. Three routes toward (+)-psiguadial B were evaluated that featured the following key steps: (1) an ortho-quinone methide hetero-Diels-Alder cycloaddition to prepare the chroman framework, (2) a Prins cyclization to form the bridging bicyclo[4.3.1]decane system, and (3) a modified Norrish-Yang cyclization to generate the chroman. Ultimately, the successful strategy employed a ring-closing metathesis to form the seven-membered ring and an intramolecular O-arylation reaction to complete the polycyclic framework of the natural product.",10.1021/acs.joc.8b00728,2018-05-04,0.5848597260150792
Synlett,(<i>S</i>)-(-)-1-Amino-2-methoxy-pyrrolidine (SAMP) and (<i>R</i>)-(+)-1-Amino-2-methoxypyrrolidine (RAMP) as Versatile Chiral Auxiliaries,"All articles of this category ( S )-(-)-1-Amino-2-methoxypyrrolidine (SAMP) and ( R )-(+)-1-amino-2-methoxypyrrolidine (RAMP) are commercially available chiral auxiliaries and have been successfully applied to asymmetric synthesis, especially bioactive natural product synthesis. [ 1 ] ( S )-(-)-1-Amino-2-methoxypyrrolidine (SAMP) and ( R )-(+)-1-amino-2-methoxypyrrolidine (RAMP ) emerged as chiral auxiliaries for a-alkylation in various application during the total synthesis of various complex organic molecules. The a-alkylation generally proceeds via the a-alkylation of SAMP/RAMP hydrazones followed by 1,2-addition and reductive N-N bond cleavage. [ 2 ] Recently SAMP/RAMP chiral auxiliaries was efficiently used as chiral auxiliaries in various important reactions, which includes the palladium catalyzed allylic substitution, [ 3 ] asymmetric synthesis of substituted b-formyl d-lactones and furofuran lactones, [ 4 ] diastereo- and enantioselective synthesis of syn -2,3-disubstituted, 1,4-diketones, [ 5 ] diastereoselective electrophillic fluorination of enatiopure a-silylketones, [ 6 ] recemization free cleavage of ketones SAMP hydrazones, [ 7 ] diastereo-and enantioselective synthesis of various 1,2-anti tert -butyl sulfanyl amines, [ 8 ] asymmetric synthesis of g-amino nitriles and g-amino ketones [ 9 ] etc.",10.1055/s-2003-41439,2003-01-01,0.584858522464341
European Journal of Organic Chemistry,[Pd]‐Catalyzed Intermolecular Coupling and Acid Mediated Intramolecular Cyclodehydration: One‐Pot Synthesis of Indenes,"An efficient one‐pot synthesis of indenes from simple starting materials is presented. This process involves a dual C–C bond formation through an intermolecular Heck coupling reaction followed by acid‐mediated intramolecular cyclodehydration. The strategy is amenable to various substituted aromatics to give indenes. In addition, the regioselective synthesis of benzyl styrenes in a single column purification technique through in‐situ reduction of Heck products (ketones) followed by acid mediated dehydration of crude reaction mixture is presented.",10.1002/ejoc.201701622,2017-12-24,0.5848512662520322
Journal of the American Chemical Society,Asymmetric Hydrovinylation of Vinylindoles. A Facile Route to Cyclopenta[<i>g</i>]indole Natural Products (+)-<i>cis</i>-Trikentrin A and (+)-<i>cis</i>-Trikentrin B,"Vinylindoles undergo Ni(II)-catalyzed asymmetric hydrovinylation under very mild conditions (-78 °C, 1 atm ethylene, 4 mol % catalyst) to give the corresponding 2-but-3-enyl derivatives in excellent yields and enantioselectivities. Hydroboration of the alkene and oxidation to an acid, followed by Friedel-Crafts annulation, gives an indole-annulated cyclopentanone that is a suitable precursor for the syntheses of cis-trikentrins and all known herbindoles. For example, the cyclopentanone from 4-ethyl-7-vinylindole is converted into (+)-cis-trikentin A in four steps (Wittig reaction, alkene isomerization, diastereoselective hydrogenation, and nitrogen deprotection). The previous synthesis of this molecule from (S)-(-)-malic acid involved more than 20 steps and a preparative HPLC separation of diastereomeric intermediates.",10.1021/ja3004733,2012-03-06,0.5848459185200483
Organic Letters,"Efficient Approach to Fluvirucins B<sub>2</sub>−B<sub>5</sub>, Sch 38518, and Sch 39185. First Synthesis of their Aglycon, via CM and RCM Reactions","A route to fluvirucinins B(2-5) (the common aglycon of fluvirucins B(2)-B(5), Sch 38518, and Sch 39185) is reported for the first time. A ring-closing metathesis (RCM) generated the C6-C7 double bond, which by catalytic hydrogenation (in toluene) gave the desired epimer with a 9:1 diastereoselection. Azide 8a and carboxylic acid 5 came from ethyl-branched fragments C9-C13 (CHO at C9) and C1-C5 via an asymmetric allylation of the former and a cross metathesis (CM) followed by a ketone methylenation (with 20 mol % of DMF as a sacrificial additive) of the latter.",10.1021/ol901030f,2009-07-07,0.5848455600861832
Journal of Organic Chemistry,Chemoenzymatic Synthesis and Synthetic Application of Enantiopure Aminocyclopentenols:  Total Synthesis of Carbocyclic (+)-Uracil Polyoxin C and Its α-Epimer,"Carbocyclic uracil polyoxin C (+)-2 and its alpha-epimer (-)-3 were synthesized in an efficient fashion from cis-4-(N-tert-butylcarbamoyl)cyclopent-2-en-1-ol (+/-)-7. The synthesis incorporates a concise, inexpensive chemoenzymatic synthesis of enantiopure aminocyclopentenols, a Pd(0)-catalyzed substitution reaction, and a mild reduction of an alpha-nitro ester by TiCl(3)/sodium borohydride. Significantly, this process demonstrates the synthetic utility of the versatile enantiopure aminocyclopentenol building block (-)-4.",10.1021/jo0496796,2004-05-25,0.5848379485109141
Journal of the American Chemical Society,"A General Stereocontrolled, Convergent Synthesis of Oligoprenols That Parallels the Biosynthetic Pathway","A solution is reported to the classic unsolved problem of stereoselective synthesis of all-E oligoprenols, such as E-farnesylfarnesol, by a cationic coupling analogous to the biosynthetic pathway. The simplicity and efficacy of the method, which is outlined in Scheme 1, are demonstrated by the synthesis of a series of all-E oligoprenols from C(20) to C(35) in uniformly excellent overall yield. The success of the approach is due not only to the highly E-stereoselective C-C coupling that forms the oligoprenyl chain but also to the development of efficient syntheses of allylic secondary silanes and E-oligoprenal acetals, and to a selective allylic demethoxylation reaction.",10.1021/ja0127537,2002-02-20,0.5848364600716439
Angewandte Chemie International Edition,Tandem Allylboration–Prins Reaction for the Rapid Construction of Substituted Tetrahydropyrans: Application to the Total Synthesis of (−)‐Clavosolide A,Tetrahydropyrans are common motifs in natural products and have now been constructed with high stereocontrol through a three-component allylboration-Prins reaction sequence. This methodology has been applied to a concise (13 steps) and efficient (14 % overall yield) synthesis of the macrolide (-)-clavosolide A. The synthesis also features an early stage glycosidation reaction to introduce the xylose moiety and a lithiation-borylation reaction to attach the cyclopropyl-containing side chain.,10.1002/anie.201511140,2016-01-14,0.5848192526615683
European Journal of Organic Chemistry,"Synthesis of Highly Substituted Pyrrolo[1,2‐a]quinoline‐3,5‐diones through Ag(I) Catalyzed Cyclization of 4‐Hydroxyquinolinyl‐2‐ynones","Abstract An efficient synthetic route to access highly substituted pyrrolo[1,2‐a]quinoline‐3,5‐diones in which the core is formed by fusion of quinolone and pyrrolone moieties is discussed. The method involves Ag(I) catalyzed cyclization of 4‐Hydroxyquinolinyl‐2‐ynones which in turn may be accessed from kynurenic acid derivatives through Weinreb amide intermediate, followed by alkyne addition. Studies involving substrates with different substitution pattern revealed that factors increasing the nucleophilicity of quinoline nitrogen or Lewis acid‐coordination of the ynone unit gives high yields in short reaction times. It was possible to execute tandem cyclization‐arylation sequence by using Pd(II) generated by oxidative addition of Pd(0) with aryl iodide as the electrophilic species to get substitution pattern as seen in Discoipyrrole A.",10.1002/ejoc.202300894,2023-10-13,0.5848159592990396
European Journal of Organic Chemistry,Enantioselective Total Synthesis of (+)‐Stachyflin: A Potential Anti‐Influenza A Virus Agent Isolated from a Microorganism,"Abstract A novel and potent hemagglutinin inhibitor, (+)‐stachyflin, was efficiently synthesized in an enantioselective manner starting from the (+)‐5‐methyl‐Wieland–Miescher ketone. The synthetic method features a BF 3 · Et 2 O‐induced cascade epoxide‐opening/rearrangement/cyclization reaction tostereoselectively construct the requisite pentacyclic ring system in one step. In order to rationalize the mechanism of the cascade reaction, quantum chemical calculations of the possible intermediary carbocations and transition states in the model synthesis were carried out. An alternative approach to synthesize (+)‐stachyflin by employing a similar cascade reaction was also described.",10.1002/ejoc.201100173,2011-04-18,0.58481231265447
Organic Process Research & Development,"Profiling the Formation of 2-Chloro-<i>N,N</i>-dimethylamino Trimethinium Chloride Salt, a Key Intermediate in the Manufacturing Process of Etoricoxib","2-Chloro- N, N -dimethylamino trimethinium chloride salt (CDT-chloride) is a key intermediate in the synthesis of Etoricoxib, a selective COX-2 inhibitor developed by Merck & Co., Inc. The formation of CDT-chloride from a mixture of chloroacetic acid and POCl 3 in DMF was monitored by in situ IR and in situ NIR. The buildup of transient intermediates, starting material disappearance, and product/byproduct formation were effectively followed during the course of the reaction using both techniques. The observations confirmed the intermediacy of both chloroacetyl chloride and a Vilsmeier type reagent as well as document the evolution of carbon dioxide.",10.1021/op049802v,2005-01-15,0.5848106581405426
Tetrahedron,Novel and highly efficient one pot protocol for the synthesis of diversely functionalized triarylmethanes,,10.1016/j.tetlet.2014.11.139,2014-12-23,0.5848070707772256
Journal of Organic Chemistry,"2-Substituted 2,3-Dihydro-4<i>H</i>-1,3-benzoxazin-4-ones:  Novel Auxiliaries for Stereoselective Synthesis of 1-β-Methylcarbapenems<sup>1</sup>","The dihydrobenzoxazone 9e, which is easily prepared from salicylamide 11 and cyclohexanone, serves as an efficient auxiliary in the synthesis of the 1-beta-methylcarbapenem key intermediate 10. The stereocontrolled Reformatsky-type reactions of the acetoxyazetidinone 2 with the carboximides 6 gave the intermediates 7 with high diastereoselectivities in high chemical yields. The auxiliary 9e also acts as a good leaving group in the TMSCl-promoted Dieckmann-type cyclization leading to a 1-beta-methylcarbapenem skeleton. By using this auxiliary, 10 was synthesized in 58% overall yield and four steps from 2.",10.1021/jo961866j,1997-05-01,0.5848067462057043
Synlett,"A Concise Synthesis of (-)-Methylenolactocin and (-)-Phaseolinic Acid from (6<i>S</i>,9<i>S</i>)-Tetradec-7-yne-6,9-diol","All articles of this category A novel, stereodivergent route to paraconic acids from C 2 -symmetric trans - and cis -alk-2-ene-1,4-diols through Ireland-Claisen and/or Johnson orthoester rearrangements is disclosed. This strategy has been applied to the synthesis of (-)-methylenolactocin and (-)-phaseolinic acid from a single chiral diol. rearrangements - lactones - stereoselective synthesis - reductions",10.1055/s-2001-9720,2001-12-31,0.5847932775196865
Organic Letters,Ring-Construction/Stereoselective Functionalization Cascade: Total Synthesis of Pachastrissamine (Jaspine B) through Palladium-Catalyzed Bis-cyclization of Bromoallenes,"Palladium(0)-catalyzed cyclization of bromoallenes bearing hydroxyl and benzamide groups as internal nucleophiles stereoselectively provides functionalized tetrahydrofuran. With this bis-cyclization as the key step, a short total synthesis of pachastrissamine, a biologically active marine natural product, was achieved.",10.1021/ol901904w,2009-09-09,0.5847883871803499
Organic Letters,BF<sub>3</sub>-Promoted Synthesis of Diarylhexahydrobenzo[<i>f</i>]isoquinoline,"An easy and straightforward synthesis of 6,10b-diarylhexahydrobenzo[f]isoquinoline by the repeated treatment of boron trifluoride etherate (BF(3) x OEt(2)) is reported. The overall transformation from 4-arylpiperidin-3-one to benzo[f]isoquinoline proceeds via ring contraction, chain elongation, and intramolecular electrophilic cyclization in moderate yields. It presents a novel rearrangement reaction catalyzed by boron trifluoride etherate and broadens the scope of application.",10.1021/ol100072n,2010-03-01,0.5847872448608517
Synlett,The Catalytic Asymmetric Claisen Rearrangement (CAC) in Natural Product Synthesis: Synthetic Studies toward Curvicollides A-C,A catalytic asymmetric Claisen rearrangement has been utilized as key C-C connecting transformation for the synthesis of a building block in the projected total synthesis of the fungicidal polyketides curvicollide A-C.,10.1055/s-2005-922789,2005-12-20,0.5847732901459681
Angewandte Chemie International Edition,Total Synthesis of Auripyrone A Using a Tandem Non‐Aldol Aldol/Paterson Aldol Process as a Key Step,"To aldol or non-aldol: The titled reaction sequence generates the polypropionate 3 from the epoxy alcohol 1 and the ketone 2 as a single diastereomer. Compound 2 was used for an efficient synthesis of auripyrone A using a highly regioselective hemiketalization of a keto diol and a late-stage spiroketalization onto a stable hemiketal as the final key steps. TBDPS=tert-butyldiphenylsilyl, Bz=benzoyl, TES=trietyhlsilyl.",10.1002/anie.200904607,2009-10-12,0.5847708293472589
European Journal of Organic Chemistry,Chemoenzymatic Synthesis of δ‐Keto β‐Hydroxy Esters as Useful Intermediates for Preparing Statins,"Enantiopure ( R )‐3‐hydroxy‐5‐oxohexanoic acid esters have proven to be useful intermediates in the synthesis of the side chain of statins, in view of the recently described preparation of rosuvastatin and other statins through aldol reactions. Herein, an improved synthesis of these intermediates, by combining chemical and enzymatic reactions, is described. In particular, the selective reduction of a δ‐ketal β‐keto ester was identified as a key step to obtain derivatives with satisfactory optical purities for use in the synthesis of statins.",10.1002/ejoc.201600268,2016-05-20,0.5847707778615203
European Journal of Organic Chemistry,Total Synthesis of a Pancratistatin/Shikimic Acid Hybrid Analogue,"Abstract Pancratistatin and structurally related narciclasine are natural products of great interest as they display potent and selective activities against various diseases. A concise synthesis of a functionalised pancratistatin framework, via a Heck reaction and subsequent cyclisation, is reported. The unfunctionalised model core of pancratistatin was synthesised from 1‐cyclohexene‐1‐carboxylic acid in two steps in 50 % yield. A modified route was then successfully applied to (−)‐shikimic acid to afford a novel pancratistatin/shikimic acid hybrid analogue that possesses three stereo‐defined hydroxyl groups in the C‐ring.",10.1002/ejoc.202301247,2024-01-18,0.5847684453664516
Journal of Organic Chemistry,Synthetic Studies toward Highly Functionalized 5β-Lanosterol Derivatives:  A Versatile Approach Utilizing Anionic Cycloaddition,Stereoselective synthesis of the potentially biologically valuable 5beta-lanosteroidal-type backbone was achieved via anionic cycloaddition. Synthesis of the two new bicyclic Nazarov intermediates 14 and 40 and their cycloaddition with chiral cyclohexenone 25 and further functional group manipulations resulted in highly functionalized tetracyclic intermediates 28 and 44. These synthetic intermediates could lead to the total synthesis of new lanosterol-based inhibitors.,10.1021/jo0608725,2006-07-01,0.5847645506113784
Tetrahedron,The synthesis and subsequent oxidation of tetrahydrochroman. A new lactone synthesis,,10.1016/s0040-4039(00)90445-3,1964-01-01,0.5847636069935224
Angewandte Chemie International Edition,A New Oxocarbon C<sub>12</sub>O<sub>6</sub> via Highly Strained Benzyne Intermediates,Some fine arynes: Elimination of triflate followed by [2+2] cycloaddition with ketene silyl acetals facilitates the formation of highly strained benzynes with one or two annulated cyclobutane rings. A prominent example based on this chemistry is the synthesis of the novel oxocarbon C12O6 (see structure).,10.1002/anie.200700926,2007-05-16,0.5847613532725735
European Journal of Organic Chemistry,Function‐Oriented Synthesis of a Didesmethyl Triazacryptand Analogue for Fluorescent Potassium Ion Sensing,"Abstract Triazacryptand (TAC)‐based fluorescent K + sensors have broad biomedical utility, yet their advancement has been hindered because of their challenging synthesis. Herein, an efficient synthesis is reported that delivers a didesmethyl triazacryptand (ddTAC) K + sensor in twofold fewer steps and ninefold higher overall yield than the original TAC synthesis. Our synthesis utilizes a C–O dianionic oxidative macrocyclization and reports new examples of aminoarylations and a microwave route to xanthythilium chromophores. The K + sensitivity and selectivity of the ddTAC‐based sensor are comparable to the TAC‐based sensor.",10.1002/ejoc.201001450,2011-01-17,0.5847603125186012
Organic Letters,Total Syntheses of (±)-Securinine and (±)- Allosecurinine,Total syntheses of (±)-securinine and (±)-allosecurinine that employ a tandem rhodium carbenoid-initiated Claisen/α-ketol rearrangement sequence as a key step are described.,10.1021/ol3020072,2012-08-22,0.5847580565959439
Synthesis,A Convenient Synthesis of (±)-4-Prenylpterocarpin,"All articles of this category Coupling of 7-methoxy-8-(3-methyl-2-butenyl)-2 H -1-benzopyran ( 4a ) with 2-chloromercurio-4,5-methylenedioxyphenol ( 5 ) yields (±)-6a, 12a- cis -dihydro-3-methoxy-4-(3-methyl-2-butenyl)-6 H -[1,3]dioxolo [5,6]benzofuro[3,2- c ][1]benzopyran ( 6 ; ±-4-prenylpterocarpin) in an efficient manner. An improved procedure for the preparation of chromenes is reported.",10.1055/s-1992-26257,1992-01-01,0.5847564525009388
European Journal of Organic Chemistry,An Oxidation–Amidation Approach for the Synthesis of Glycuronamides,"Abstract A route for the synthesis of glycuronamides via the intermediacy of 6‐ S ‐tolyl‐substituted glycosides and uronic acid thioesters, is reported. The route, which is compatible with a variety of carbohydrate residues and protecting groups, was used to synthesize the repeating unit of the E. coli K54 capsular polysaccharide.",10.1002/ejoc.201600239,2016-05-01,0.5847516274903206
Journal of Organic Chemistry,Asymmetric Synthesis of Tetracyclic Benzo[<i>a</i>]quinolizidine Targets,"We report a novel, facile, and asymmetric approach for the synthesis of polycyclic benzo[ a]quinolizidine targets. In the formation of more functionalized derivatives, we have observed the generation of an iminium ether salt intermediate, formed during an unprecedented retro-Diels-Alder/ N-acyliminium cyclization cascade. The iminium ether intermediate was isolated in good yield, characterized by X-ray crystallography, and subsequently applied as a synthetic building block.",10.1021/jo801019h,2008-07-18,0.58474843036061
Tetrahedron,A convergent synthesis of novel conformationally restricted HIV-1 protease inhibitors,,10.1016/s0040-4039(00)77051-1,1994-07-01,0.5847453925467186
Synthesis,Total Synthesis of Soraphen A1α,All articles of this category The convergent synthesis of macrolide soraphen A 1α is described starting from glucose (western part) and mannose (eastern part). Mannose was converted into a 2-deoxyribohexapyranoside that could be methylated and reduced stereoselectively. Chain elongation at C-6 was carried out by stereoselective addition of a magnesium acetylide. The two fragments (western and eastern) were assembled by a Julia olefination followed by macrolactonization. The introduction of the methyl group at C-2 of norsoraphen occurred stereoselectively for thermodynamic reasons. Soraphen A 1α - macrolide - Julia olefination - chiral pool,10.1055/s-1999-3671,1999-01-01,0.5847365509576161
Synlett,"Stereodivergent Synthesis of Carbasugars from D-Mannose. Syntheses of 5a-Carba-α-D-allose, β-L-Talose, and α-L-Gulose Pentaacetates","A stereodivergent entry to 5a-carba-d- and l-pyranoses from a single precursor is described. The approach is based on the selective deoxygenation of polyoxygenated methylcyclohexane intermediates, readily available from radical cyclization of d-mannose derivatives. This strategy has been applied to the preparation of 5a-carba-α-d-allo-, 5a-carba-β-l-talo-, and 5a-carba-α-l-gulopyranose pentaacetates.",10.1055/s-2002-31900,2002-01-01,0.5847358785504659
Tetrahedron,Synthesis of novel spirocyclic cocaine analogs using the Suzuki coupling,,10.1016/s0040-4039(00)00113-1,2000-03-01,0.5847335044842157
Journal of Organic Chemistry,"A Concise Approach to Enantioselective Synthesis of Euolutchuols A, B, and D and Their Structure Assignment","We demonstrated the first enantioselective total syntheses and structural assignment of euolutchuols A, B, and D. The syntheses begin with a biomimetic cationic polyene cyclization of epoxy-polyene, yielding the natural product β-hydroxy-8,11,13,15-abietatetraene, which serves as the starting material for all euolutchuols. Two alternative methods, enantioselective copper-catalyzed hydroboration and oxidation, as well as Sharpless dihydroxylation and reductive deoxygenation, were employed to construct the 15-methyl stereogenic center, and stereochemistry is established by X-ray analysis. Selective synthetic methods are employed to install 12-hydroxy and 2-oxo groups to produce euolutchuols B and D.",10.1021/acs.joc.5c02500,2025-12-22,0.5847323227432436
Tetrahedron,Oxazoline-mediated synthesis of the Gossypium sesquiterpene lacinilene C-7 methyl ether and a structurally Related HIV-1 Reverse Transcriptase Inhibitor,,10.1016/s0040-4039(00)79206-9,1993-06-01,0.5847290655430273
Synthesis,Enantiomeric Synthesis of the SPIKET-P Enantiomers,"A convenient synthesis of the antipodes of the title compound has been developed starting from (R)-1,2,5,6-dicyclohexylidene mannitol. Some of the key features of the syntheses were simple reaction protocols, and stereoselective inversion of chiral 1,2-diol moiety via neighbouring group assisted acetylation.",10.1055/s-2004-822342,2004-01-01,0.5847263898233311
Organic Letters,Total Synthesis and Stereochemical Confirmation of Heliolactone,"Until now, the relative stereochemistry of the noncanonical strigolactone, heliolactone, has remained ambiguous. The total synthesis of heliolactone is described, with the key bond-forming event being a Stille cross-coupling that relied upon a reversal of the nucleophile-electrophile coupling partners. Spectroscopic analysis of synthetic heliolactone (and other stereoisomers) and comparisons with the isolated material enabled the absolute and relative stereochemistry of heliolactone to be secured.",10.1021/acs.orglett.9b01402,2019-05-13,0.5847247182794103
Tetrahedron,"Copper-catalyzed one-pot N-alkenylation and N-alkylation of amides: an efficient synthesis of substituted 2,3-dihydropyrroles",,10.1016/j.tetlet.2007.07.221,2007-08-09,0.5847230034042408
Journal of Organic Chemistry,Two-Step Synthesis of Substituted 3-Aminoindazoles from 2-Bromobenzonitriles,A general two-step synthesis of substituted 3-aminoindazoles from 2-bromobenzonitriles involving a palladium-catalyzed arylation of benzophenone hydrazone followed by an acidic deprotection/cyclization sequence is described. This procedure offers a general and efficient alternative to the typical S(N)Ar reaction of hydrazine with o-fluorobenzonitriles.,10.1021/jo100243c,2010-03-17,0.5847155780707369
Tetrahedron,"Synthesis of -β-(isoxazolin-5-one-2-yl)-alanine: a novel method for the synthesis of -substituted 3,4-unsubstituted isoxazolin-5-ones",,10.1016/s0040-4039(00)98264-9,1985-01-01,0.5847144110336736
Journal of Organic Chemistry,Syntheses of (−)-Tripterifordin and (−)-Neotripterifordin from Stevioside,"We report short syntheses of (-)-tripterifordin and (-)-neotripterifordin, potent inhibitors of HIV replication, from stevioside, a natural sweetener used worldwide. The key transformations are reduction at C13 through the formation of a tertiary chloride and subsequent three-step lactonization including a selective iodination at C20 by the photoreaction of the C19-alcohol. The title compounds were reliably obtained from stevioside in 9 and 11 steps (with 5-7 isolation steps), respectively. Additionally, the related lactone-containing ent-kaurenes, doianoterpenes A and B, and two more natural products were synthesized.",10.1021/acs.joc.7b02916,2018-01-12,0.5847125879729974
European Journal of Organic Chemistry,Synthesis and Chiral Resolution of <i>C</i><sub>3</sub>‐Symmetric Tribenzotriquinacenes,"The synthesis and chiral resolution of a C 3 ‐symmetric triaminotribenzotriquinacene is reported. Both enantiomers were obtained in good yields and excellent enantiomeric purity by selective precipitation of their monodibenzoyltartrate salts. Conversion of the enantiopure ( M )‐triaminotribenzotriquinacene into a C 3 ‐symmetric triiodide highlights the usefulness of this compound as a starting point for the preparation of other enantiopure C 3 ‐symmetric tribenzotriquinacene derivatives, which may find application as building blocks for the preparation of chiral molecules in the nanosize regime.",10.1002/ejoc.201600890,2016-08-08,0.5847115142109901
Journal of Organic Chemistry,Synthetic Efforts toward the Spiroketal Core of Spirangien A,"Synthetic studies toward the spiroketal core of spirangien A are described. Two synthetic approaches were developed. Both of them use a diastereoselective aldol addition of a lithium enolate derived from a methyl ketone on an aldehyde. In the first approach, the introduction of the (E)-trisubstituted terminal olefin was achieved by using an iron-catalyzed cross-coupling between an alkyl iodide and a vinyl Grignard reagent and a randomly protected spiroketal was obtained. In the second approach, a highly functionalized spiroketal carbamate, which includes 13 stereogenic centers, was successfully isolated.",10.1021/jo100871m,2010-07-08,0.5847068923581662
Journal of Organic Chemistry,Synthesis of Azabicyclo[2.2.<i>n</i>]alkane Systems as Analogues of 3-[1-Methyl-2-(<i>S</i>)-pyrrolidinyl- methoxy]pyridine (A-84543),"This work is connected with the epibatidine field and describes the synthesis of several analogues of compounds that present affinity for nicotinic acetylcholine receptors, such as 3-[1-methyl-2-(S)-pyrrolidinylmethoxy]pyridine (A-84543). These analogues bear a 3-pyridyl ether substituent at the bridgehead carbon of the azabicyclo[2.2.n]alkane system. Particularly, in the case of the 1-substituted 2-azabicyclo[2.2.2]octane system, a new synthetic route has been developed, which involves the synthesis of a novel rigid sulfamidate that allows the straightforward introduction of nucleophiles.",10.1021/jo0700732,2007-03-20,0.5846994070273362
Tetrahedron,Synthesis of the carbonic acid benzotriazol-1-yl-ester-(2-biotinylamino)-9h-fluoren-9-ylmethyl ester: A convenient transient-biotinylation reagent for use in affinity chromatography,,10.1016/0040-4039(95)01964-j,1995-12-01,0.5846946483514288
European Journal of Organic Chemistry,Stereoselective Synthesis of (−)‐Deacetylanisomycin,"Abstract A stereoselective synthesis of (−)‐deacetylanisomycin has been achieved from a nitrone derived from L ‐threose in 6 steps and 53.7% overall yield. The key step of the synthesis is the nucleophilic addition of a Grignard derivative with complete diastereofacial selectivity. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2003)",10.1002/ejoc.200300091,2003-07-15,0.5846930009111443
Synlett,"Two-Step Synthesis of 3-Aryl-1,3-Dihydro-2<i>H</i>-imidazo[4,5-<i>b</i>]pyridin-2-ones","One-pot tandem palladium-catalysed amination and ­intramolecular amidation of tert-butyl (2-chloropyridin-3-yl)carb­amate with substituted primary anilines allows for the preparation of 3-arylated-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-ones (49-90% yield) in two steps from commercially available materials.",10.1055/s-2006-947355,2006-08-01,0.5846899987775834
Journal of the American Chemical Society,Synthesis and Structure Verification of the Vaccine Adjuvant QS-7-Api. Synthetic Access to Homogeneous<i>Quillaja saponaria</i>Immunostimulants,"QS-7-Api is an exceedingly potent immuno-adjuvant isolated from the bark of Quillaja saponaria. It is significantly less toxic than QS-21, a related saponin that is currently the favored adjuvant in anticancer and antiviral vaccine clinical trials. Tedious isolation/purification protocols and uncertainty in its structural constitution have hindered the clinical development of QS-7. A chemical synthesis of QS-7-Api is described, providing structural verification of the adjuvant. A novel semisynthetic sequence to QS-7-Api has also been established, greatly facilitating access to QS-7 for preclinical and clinical evaluation.",10.1021/ja801008m,2008-04-15,0.5846893511140356
Tetrahedron,Reductive phenolic coupling: A novel intramolecular capture of a nitro-intermediate generated through reduction of a nitrobenzophenone.,,10.1016/s0040-4039(00)61335-7,1992-08-01,0.5846803854419922
Organic Letters,Synthesis of Complex Stereoheptads en Route to Daphnane Diterpene Orthoesters,"Tricyclic cores of the daphnane diterpene orthoesters (DDOs) are synthesized in 10 steps from readily available materials. Key to their assembly is the development of a stereocontrolled p-quinol functionalization sequence which enables rapid access to DDO C-ring stereopolyads from simple precursors. Problems encountered in stereo- and regioselectivity are highlighted and solved by exact changes in choreography, although it is shown that the undesired stereochemical outcomes also proceed with high selectivity.",10.1021/acs.orglett.8b02124,2018-08-17,0.5846784720770337
Synthesis,"Furoquinolines; Part XI<sup>1</sup>. A Novel AICl<sub>3</sub>-Catalysed Rearrangement of 4-Phenyl-2,3-dihydrofuro[2,3-<i>b</i>]quinolines. A New Route to the 5,6-Benzophenanthridine System",,10.1055/s-1977-24568,1977-01-01,0.5846637083994891
Tetrahedron,"Synthesis of C15,C14′-ring locked all-trans-β-carotene",,10.1016/s0040-4039(02)00663-9,2002-05-01,0.5846586309372572
Tetrahedron,Selective synthesis of 2-aminobenzoxazoles and 2-mercaptobenzoxazoles by using o-aminophenols as starting material,,10.1016/j.tetlet.2017.09.092,2017-09-30,0.584657681737865
Tetrahedron,"Reductive amination of 1,4- and 1,5-dicarbonyl compounds with (S)-valine methyl ester. Synthesis of (S)-2-phenylpyrrolidine and (S)-2-phenylpiperidine",,10.1016/s0040-4039(00)77030-4,1994-04-01,0.5846565669426746
Tetrahedron,Design and synthesis of polycyclic bisindoles via Fischer indolization and ring-closing metathesis as key steps,,10.1016/j.tetlet.2016.10.112,2016-11-01,0.5846551330086964
Synlett,"Regio- and Diastereoselective Synthesis of a Primary β-Azidoalcohol via Stereoselective Epoxidation of a Highly Functionalised di-<i>o</i>,<i>o</i>′-Substituted Styrene: Toward a New Total Synthesis of (-)-Quinocarcin","Diastereoselective epoxidation of a highly functionalised di-o,o′-substituted styrene combined with subsequent regioselective epoxide ring-opening afforded the corresponding primary β-azidoalcohol, which is the required key intermediate for a new total synthesis approach toward (-)-quinocarcin and various unnatural d-ring modified analogues.",10.1055/s-2005-871561,2005-06-22,0.5846507288392251
Tetrahedron,"Synthesis of a new dipeptide-type 5,1-benzothiazocine system",,10.1016/s0040-4039(00)80047-7,1988-01-01,0.5846414146693756
Synthesis,"A Mannich-Type Cyclisation to Thiazepines. Synthesis of Pyrimido[5,4-<i>f</i>]benzo[<i>b</i>]-1,4-thiazepines, a New Tricyclic System",,10.1055/s-1977-24310,1977-01-01,0.5846414146693756
European Journal of Organic Chemistry,Synthesis of Atorvastatin Lactone Linker Constructs for Target Fishing,"Abstract With the aim of connecting atorvastatin lactone 9 to a linker for affinity‐based target fishing, a concise route to the pyrrolecarboxylic acid 8 was developed. Key features of the synthesis of the diol‐containing side‐chain were a catalytic enantioselective vinylogous aldol reaction resulting in 5‐hydroxy‐enoate 14 (88 % ee ). Subsequent intramolecular oxa‐Michael addition and amide reduction furnished key building block 5 . As we have described previously, Paal–Knorr reaction of amine 5 with diketone 6 led to pyrrole 7 , which – after carboxylation – provided acid 8 . Since atorvastatin lactone is an aniline derivative of acid 7 , we prepared two linkers having an aniline terminus. For this purpose ethylene glycol based allyl ethers 20 and 27 were combined with nitrostyrene 22 by cross‐metathesis. After hydrogenation of the nitro group and the double bond, anilines 25 and 29 , respectively, were obtained. The anilines were condensed with carboxylic acid 8 to afford the corresponding amides 30 and 35 . Elaboration of the side‐chain then provided atorvastatin lactone linker constructs 34 and 39 , respectively.",10.1002/ejoc.201201154,2012-10-15,0.5846368976974341
Tetrahedron,Suppression of the Mattox rearrangement of 16α-cyanoprednisolones in acid: Synthesis of methyl 16α-prednisolonecarboxylates,,10.1016/0040-4039(95)00526-i,1995-05-01,0.5846359947616596
Journal of Organic Chemistry,"Two-Step Benzo[<i>e</i>]indole Core Assemblage from Three 1<i>H</i>-1,2,3-Triazole Molecules via “Transannulation/C–H Insertion/S<sub>E</sub>Ar–Cyclization” Sequence","A two-step synthesis of fluorescent 2,3-dihydrobenzo[ e ]indole derivatives using only 1 H -1,2,3-triazoles as starting materials was developed. At the first step of the synthesis, the 1-alkyl-1,2,3-triazole reacts with two 1-sulfonyl-1,2,3-triazole molecules via the domino transannulation/sulfonamidovinylation sequence under rhodium catalysis. The reaction involving two different 1-sulfonyltriazoles is accomplished in one pot. The further S E Ar cyclization of the formed 4-aryl-5-(sulfonamidovinyl)pyrroles using Eaton’s reagent provides 2,3-dihydrobenzo[ e ]indoles having a sulfonylimino-, hydroxy-, and primary amino groups at the C1, C2, and C5 positions, respectively.",10.1021/acs.joc.5c00567,2025-05-31,0.5846330365560974
Tetrahedron,"A stereocontrolled approach for the synthesis of 2,5-diaryl-3,4-disubstituted furano lignans through a highly diastereoselective aldol condensation of an ester enolate with an α-chiral center: total syntheses of (−)-talaumidin and (−)-virgatusin",,10.1016/j.tetlet.2008.03.105,2008-03-29,0.5846316093158889
Organic Process Research & Development,Scale-Up and Development of a One-Step Process for the Synthesis of Succinylcholine,"Succinylcholine chloride is a neuromuscular blocking agent identified as an essential medicine by the World Health Organization. This article describes a practical synthesis and scale-up of this active pharmaceutical ingredient (API) from readily available starting materials. Analytical methods were developed to identify and quantify impurities in the API. In addition, process development resulted in practical isolation and purification procedures, which avoid the need for a recrystallization step. The process has been scaled up to 25 g reproducibly in three batches, giving an average 89% overall yield and purity meeting USP and ICH guideline specifications for API-quality succinylcholine.",10.1021/acs.oprd.3c00322,2023-12-12,0.5846312498099359
Organic Process Research & Development,Improved Synthesis of Fluticasone Propionate,"A novel process for the preparation of fluticasone propionate ( 1 ), a corticosteroid, is reported. In this paper, compound 2 was used as starting material to prepare 6 by using NaClO or NaBrO which was much cheaper than H 5 IO 6 as an oxidizing agent. Furthermore, toxic, expensive, and pollutive BrCH 2 F was replaced by AgNO 3 and Selectfluor in decarboxylative fluorination.",10.1021/op5001226,2014-07-24,0.5846247791881394
Tetrahedron,"A facile synthesis of the key intermediate for penems, carbapenems, and related β-lactam antibiotics",,10.1016/0040-4039(96)01157-4,1996-07-01,0.5846211520268084
Organic Process Research & Development,An Efficient and Selective 1-<i>N</i>-Monoethylation of Sisomicin:  Process Development of Netilmicin,"With a new reagent developed for the selective monoethylation at the 1-amino group of sisomicin ( 1 ), a new process suitable for the mass production of netilmicin under conditions less sensitive to air and moisture has also been developed. Three of the amino groups, at the C-3, C-2‘, and C-6‘ positions of the four amino groups of sisomicin, were selectively protected by using Zn(OAc) 2 and acetic anhydride in methanol. Development efforts focused on optimising the conditions for ethylation to give an improved product (96% yield) according to the new and concise synthetic route.",10.1021/op000076f,2002-01-01,0.5846137622731854
Tetrahedron,"A Keggin heteropoly acid as an efficient catalyst for an expeditious, one-pot synthesis of 1-methyl-2-(hetero)arylbenzimidazoles",,10.1016/j.tetlet.2007.05.144,2007-06-01,0.5846093535691171
Tetrahedron,New synthesis of multi-substituted α-chlorocyclobutanones from 1-chloro-3-cyanoalkyl p-tolyl sulfoxides by 4-Exo-Dig nucleophilic ring closure of magnesium carbenoids to nitrile group as the key reaction,,10.1016/j.tetlet.2012.03.127,2012-04-04,0.5846056909232337
Angewandte Chemie International Edition,Asymmetric Double Hydroxycarbonylation of Alkynes to Chiral Succinic Acids Enabled by Palladium Relay Catalysis,"A Pd-catalyzed asymmetric double hydroxycarbonylation of terminal alkynes was developed by using relay catalysis, providing a highly efficient route to chiral succinic acids (41 examples, 76-94 %, 94-99 % ee). Key to success was the combinatorial use of a Pd precursor with two distinct phosphine ligands in one pot. The synthetic utilities of this protocol were showcased in the facile synthesis of key intermediates for chiral pharmaceuticals.",10.1002/anie.202204156,2022-05-07,0.5846051661006885
Synthesis,"Cyclization of Bifunctional 3,5-Diamino-1<b><i>H</i></b>-1,2,4-triazole-1-carboximidamide, 5-Amino-3-hydrazinotriazole and 3,6-Diguanidino-1,2,4,5-tetrazine: A One-Step Route to Fluorinated Heteropolycycles","A series of new fluorine-containing triazolylpyrimidines and pyrimidinoaminotetrazines results from one-pot reactions of 3,5-diamino-1H-1,2,4-triazole-1-carboximid­amide hydrochloride and 1,4-diguanidino-2,3,4,5-tetrazine with fluoro-1,3-diketones. Bicyclization of a variety of fluorinated 1,3-diketones gave three fluorinated heterocyclic pyrazolo[1,2,4]triazolo[1,5-a]pyrimidines in moderate yield in a single step.",10.1055/s-2008-1067047,2008-05-26,0.584601317467037
Synlett,"A Practical Approach for Enantio- and Diastereocontrol in the Synthesis of 2,3-Disubstituted Succinic Acid Esters: Synthesis of the pan-Notch Inhibitor BMS-906024","An oxidative intermolecular enolate heterocoupling reaction was employed for the synthesis of anti -2,3-disubstituted succinic acid mono- and differentially protected diesters. Tactical approaches to access all the diastereomers are discussed. The method was applied to the synthesis of a potent anticancer agent, BMS-906024.",10.1055/s-0035-1561636,2016-05-18,0.5845964885009531
Tetrahedron,"Fries rearrangement: scalable synthesis of key fluoro building blocks 3-fluoro-4-methoxybenzoyl chloride and 1,2-diethoxy-3-fluorobenzene",,10.1016/j.tetlet.2014.02.119,2014-03-06,0.5845861867147906
Journal of Organic Chemistry,"Synthesis of 1,3-Dioxepine-Fused (Tricyclic) Bispyrazoles Involved with Pyrazolone Derivatives and Dichloromethane","A simple and novel method for the synthesis of novel 1,3-dioxepine-fused (tricyclic) bispyrazoles is described. It involves a Cs 2 CO 3 -mediated O -alkylation of readily available pyrazolone derivatives with dichloromethane as the methylene source followed by PhI(OAc) 2 -mediated intramolecular oxidative biheteroaryl coupling under mild conditions. This scalable protocol was applied for the preparation of valuable and novel 1,3-dioxepine-fused (tricyclic) bispyrazoles that could find applications in medicinal or material chemistry.",10.1021/acs.joc.1c03121,2022-03-09,0.5845818784728757
Synthesis,"Synthesis of Pyrido[2,3-<i>d</i>]pyrimidines and Fused Tetracyclic Derivatives from Methyl<i>N</i>-Aryldithiocarbamates",,10.1055/s-1984-30900,1984-01-01,0.5845796844661951
Tetrahedron,"Synthesis of tribromobenzofuran and tribromobenzopyran derivatives from methyl 2-allyl-4,5,6-tribromo-3-hydroxybenzoate",,10.1016/j.tetlet.2006.11.005,2006-11-22,0.5845796844661951
European Journal of Organic Chemistry,Total Synthesis of Neoaltenuene,"Abstract The total synthesis of neoaltenuene, a toxin produced by alternaria fungi, has been achieved for the first time in 14 steps in a yield of 10 % starting from quinic acid and phloroglucinic acid, the longest linear sequence consisting of 10 steps. The key reaction was a palladium‐catalyzed Suzuki‐type coupling of an arene boronate with an iodinated cyclohexene.4a‐ epi ‐Neoaltenuene, a non‐natural isomer has been synthesized similarly. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2009)",10.1002/ejoc.200900125,2009-03-24,0.5845788687744556
Journal of Organic Chemistry,Perylenequinone Natural Products: Total Syntheses of the Diastereomers (+)-Phleichrome and (+)-Calphostin D by Assembly of Centrochiral and Axial Chiral Fragments,"The first total synthesis of (+)-calphostin D and the total synthesis of (+)-phleichrome are outlined. The convergent syntheses utilize an enantiopure biaryl common intermediate, which is formed via an enantioselective catalytic biaryl coupling. The established axial chirality is transferred to the perylenequinone helical stereochemistry with good fidelity. Additionally, efforts focused on the installation of the stereogenic C7,C7'-2-hydroxypropyl groups. Three routes were evaluated to establish the C7,C7'-stereochemistry, in which the successful route involved a double epoxide alkylation with a complex axial chiral biscuprate. This strategy not only allowed the synthesis of the unnatural isomers of calphostin D and phleichrome for assessment in biological systems but also provided valuable information for the syntheses of the more complex cercosporin and hypocrellin A.",10.1021/jo901384h,2009-11-09,0.5845757767250734
Angewandte Chemie International Edition,Synthesis of Azadirachtin: A Long but Successful Journey,"22 Years in the making: Azadirachtin (1) was synthesized for the first time by a highly convergent approach, utilizing a Claisen rearrangement and a radical cyclization as key steps. End-game strategies relied on intermediate 2, which could be obtained by synthetic methods as well as by degradation of 1. Bn=benzyl, TBS=tert-butyldimethylsilyl.",10.1002/anie.200703027,2007-07-30,0.5845712838296432
Tetrahedron,Toward the synthesis of tetrodecamycin: asymmetric synthesis of a direct precursor of the C6C18 trans-decalin portion,,10.1016/s0040-4039(03)00339-3,2003-03-01,0.5845687330531334
Tetrahedron,Synthesis of a potent inhibitor of β-glucuronidase,"A new glucuronic acid-type iminosugar in which a nitrogen atom is placed in the anomeric positon was synthesized and was proven to potently inhibit β-glucuronidase, with Ki = 79 nM.",10.1016/0040-4039(96)00422-4,1996-04-01,0.584566600695277
Synthesis,"5,6-Dihydro-4<i>H</i>-1,2-oxazines in Organic Synthesis: Catalytic Hydrogenation of [(5,6-Dihydro-4<i>H</i>-1,2-oxazin-3-yl)methyl]malonates to Methyl 7-Oxo-1-oxa-6-azaspiro[4.4]nonane-8-carboxylates","[(5,6-Dihydro-4H-1,2-oxazin-3-yl)methyl]malonates undergo a cascade transformation into substituted methyl 7-oxo-1-oxa-6-azaspiro[4.4]nonane-8-carboxylates under catalytic hydrogenation conditions over Raney nickel. A mechanistic scheme involving initial N-O bond cleavage with the formation of imines as key intermediates is suggested.",10.1055/s-2008-106003,2008-04-01,0.5845663205690521
Tetrahedron,"The synthesis of 3-methyl- and 3,4-dimethyltetrahydroisoquinolines by intramolecular hydroamination with n-butyllithium",,10.1016/j.tetlet.2004.10.155,2004-11-12,0.584562651438917
Organic Letters,Synthetic Study on Pactamycin: Stereoselective Synthesis of the Cyclopentane Core Framework,"The cyclopentane core framework 23 of pactamycin ( 1 ) was synthesized in 14 steps from symmetric cyclohexadiene 11 . Our synthetic strategy features Rh-mediated catalytic desymmetrization of 10 via aziridination and then regioselective ring-opening reaction of sulfonylaziridine 9 with NaN 3, ring-contraction of cyclohexene 14 by ozonolysis followed by intramolecular aldol reaction, and stereoselective construction of the sequential tetrasubstituted carbons by dihydroxylation and methylation reaction. Stereospecific incorporation of amine on tetrasubstituted carbon was achieved by Curtius rearrangement and subsequent carbamide formation.",10.1021/acs.orglett.7b01257,2017-06-12,0.5845574562584789
Journal of the American Chemical Society,Highly Efficient Enantioselective Synthesis of Chiral Sulfones by Rh-Catalyzed Asymmetric Hydrogenation,"A highly efficient and enantioselective Rh-( R, R)-f-spiroPhos complex catalyzed hydrogenation of a series of unsaturated sulfones has been developed. With Rh-( R, R)-f-spiroPhos catalyst under mild conditions, not only the asymmetric hydrogenation of both the 3,3-diaryl and exocyclic α,β-unsaturated sulfones was first realized with up to 99.9% ee but also 3-alkyl-3-aryl and benzo[ b]thiophene-1,1-dioxides were successfully hydrogenated to the corresponding chiral sulfones with excellent enantioselectivities (up to 99.4% ee) regardless of the steric hindrance, electronic property, and geometry of the substrates. Moreover, this reaction offers a route to ( S)-(+)- ar-turmerone as a spice flavor, which is an important synthetic intermediate of pharmaceuticals.",10.1021/jacs.8b12657,2019-01-07,0.5845566021420379
Organic Letters,Synthesis of Cyclohexanones through a Catalytic Cationic Cyclization of Alkynols or Enynes,"A novel procedure for the synthesis of cyclohexanones from alkynol or enyne derivatives through a cationic cyclization has been developed. The key points to obtain the six-membered ring derivatives are the use of starting materials containing a terminal alkyne, the use of tetrafluoroboric acid as a promoter of the cationic cyclization, and the appropriate selection of 1,1,1,3,3,3-hexafluoropropan-2-ol (HFIP) as solvent. This strategy can be extended to the biomimetic cationic cyclization of several terpene-derived polyenynes.",10.1021/acs.orglett.8b00437,2018-03-07,0.584554406549448
European Journal of Organic Chemistry,Survey of Synthetic Approaches to Natural (Peyssonenynes) and Unnatural Acetoxyenediynes,"Abstract Four convergent synthetic approaches to acetoxyenediynes have been explored to gain access to peyssonenynes A and B, which are natural products isolated from the red alga Peyssonelia caulifera . After optimization of the routes with a palmitic acid based model system, the synthesis of the peyssonenynes was completed by using, as the key steps, 1) Ni/Cu co‐catalyzed cross‐coupling of terminal alkynes, 2) Sonogashira cross‐coupling, 3) the addition of a diynyl anion to a Weinreb amide, and 4) the previously reported Cadiot–Chodkiewicz cross‐coupling reaction. Because bulky amide bases stereoselectively provided the ( E )‐ and ( Z )‐acetoxyenynes from the precursor ynones, the cross‐coupling routes to obtaining the acetoxyenediynes by using these stereochemically homogeneous intermediates are comparable to the alternatives in which enolacetate formation of the acetoxyenediyne motif takes place at a late stage in the synthesis.",10.1002/ejoc.201200246,2012-07-13,0.5845465515884569
Synlett,An Improved Synthesis of (-)-Martinellic Acid via Radical Addition-Cyclization-Elimination Reaction of Chiral Oxime Ether,"A concise formal synthesis of (-)-martinellic acid has been accomplished by preparing optically active dipyrroloquinoline as a key synthetic intermediate, which was prepared via the radical addition-cyclization-elimination of oxime ether carrying an unsaturated ester followed by two chemoselective reductions of the carbonyl groups.",10.1055/s-2006-939046,2006-03-14,0.5845442233827488
Tetrahedron,"Reductive alkylation of thioureas: a highly practical synthesis of unsymmetrical N,N′-disubstituted thioureas",,10.1016/j.tetlet.2004.08.182,2004-09-24,0.5845441475619668
Organic Letters,"Direct, One-Step Synthesis of Condensed Heterocycles:  A Palladium-Catalyzed Coupling Approach",[reaction: see text] A palladium-catalyzed one-step synthesis of fused aromatic heterocycles from bifunctional bromoenoates or bromoalkyl indoles and iodoarenes is reported. This method provides an efficient route to a wide variety of substituted polycyclic aromatic and heteroaromatic compounds from readily accessible starting materials.,10.1021/ol061404k,2006-07-13,0.5845387913575143
Green Chemistry,Enzymatic synthesis and polymerisation of β-mannosyl acrylates produced from renewable hemicellulosic glycans,A biocatalytic route for the synthesis of novel glycosyl acrylate monomers produced from hemicellulosic glycans.,10.1039/c8gc03947j,2019-01-01,0.5845381674405804
Tetrahedron,Efficient synthesis of an enantiomeric pair pinpinidine: An illustration of organochemical carving on the rigid bridged system as the stereochemical tactics,,10.1016/0040-4039(96)00990-2,1996-07-01,0.5845379020471299
Organic Letters,Application of Enantioselective Radical Reactions:  Synthesis of (+)-Ricciocarpins A and B,"Enantioselective synthesis of (+)-ricciocarpins A and B has been achieved in 41 and 45% overall yields, respectively, starting from a beta-substituted oxazolidinone. The key steps in the strategy are an enantioselective conjugate radical addition and the addition of a furyl organometallic to a key aldehyde intermediate. [reaction--see text]",10.1021/ol0495772,2004-05-01,0.5845377965210884
Tetrahedron,Stereoselective total synthesis of palmyrolide A via intramolecular trans N-methyl enamide formation,,10.1016/j.tetlet.2016.08.054,2016-08-24,0.5845368013242752
Synlett,A Convenient Synthesis of Quinolin-2(1<i>H</i>)-one Ring System as Precursor of Active Drugs,A series of new substituted quinolin-2(1H)-ones was prepared in good yields according to a two-step synthesis using TDAE methodology from substituted o-nitrobenzyl chlorides ­followed by a reduction-cyclization step.,10.1055/s-2004-837227,2005-01-01,0.5845351558291929
Tetrahedron,"Design and synthesis of (2-(5-chloro-2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)cyclopropyl)methanamine as a selective serotonin 2C agonist",,10.1016/j.tetlet.2015.01.060,2015-01-14,0.5845338749472425
Tetrahedron,Triacetic acid lactone as a common intermediate for the synthesis of 4-hydroxy-2-pyridones and 4-amino-2-pyrones,,10.1016/j.tetlet.2016.02.043,2016-02-12,0.5845338450334902
Tetrahedron,Efficient asymmetric synthesis of a functionalized Δ2-pyrazoline,,10.1016/s0040-4039(00)01582-3,2000-11-01,0.584533141860718
European Journal of Organic Chemistry,"Sequential Formal [4+1]‐Cycloaddition, C−H Functionalization and Suzuki–Miyaura Cross‐Coupling for the Synthesis of Trisubstituted Isoxazolines","Abstract Suzuki–Miyaura cross‐coupling reaction of 3‐bromomethyl isoxazolines with arylboronic acids was suggested as final C−C bond forming step in convenient diastereoselective route to trisubstituted isoxazolines. The required bromides were readily available from nitroalkenes and sulfonium ylides through an efficient sequence of formal [4+1]‐cycloaddition and C−H functionalization of intermediate isoxazoline N ‐oxides. The synthetic utility of the obtained isoxazolines was demonstrated by their conversion into valuable products such as hydroxy ketone, pyrrolidinone, etc.",10.1002/ejoc.202100313,2021-04-07,0.5845294967513107
Synlett,A General and Efficient Synthesis of 2-Substituted Oxazolopyridines,"Starting from commercially available halonitropyridines and haloaminopyridines, 2-substituted-oxazolo[5,4-b]pyridines, and 2-aryl-oxazolo[4,5-b]pyridines were synthesized in good yields by using a Cu(I)-mediated cyclization of halopyridylamides as a key step.",10.1055/s-0028-1088149,2009-03-20,0.5845281884602719
Synthesis,A Facile Synthesis of Acyclo-C-nucleoside Analogues from 2(3)-Formylglycals,"The reaction of 2(3)-formylglycals with malononitrile afforded push-pull butadienes with a sugar moiety. The treatment of these branched-chain sugars with ammonia yielded nicotinonitrile acyclo-C-nucleosides. Furthermore, a one step ring transformation of 2(3)-formylglycals with N-aryl-acetoacetanilides to give pyridone acyclo-C-nucleosides is described.",10.1055/s-2001-16761,2001-01-01,0.5845272134475126
Synthesis,"Stereoselective Synthesis and Applications of Pinane-Based Chiral 1,4-Amino Alcohol Derivatives","Abstract A new library of pinane-based 1,4-amino alcohols was synthesised and utilised as chiral ligands in enantioselective diethylzinc addition to benzaldehyde. Aldol condensation of (+)-nopinone, derived from (–)-β-pinene, with 2-pyridinecarboxaldehyde gave the key intermediate α,β-unsaturated ketone, which was transformed in diastereoselective reduction, followed by hydrogenation, resulting in 1,4-amino alcohols. On the other hand, epoxidation of the α,β-unsaturated ketone, followed by reduction and then hydrogenation of the pyridine ring, afforded a mixture of 4-amino-2,3-epoxy-1-ols. Stereoselective hydride reduction of the epoxy ketone and subsequent condensation of the resulting products with substituted benzyl bromides provided quaternary ammonium salts, which were subjected to hydride reduction and then hydrogenation, affording 4-amino-2,3-epoxy-1-ol derivatives containing an N-benzylpiperidine moiety. The inhibition of nucleophile-initiated opening of the oxirane ring was interpreted by a systematic series­ of comparative Hartree–Fock modelling study using the 6-31+G(d,p) basis set. The antiproliferative activities of 4-amino-2,3-epoxy­-1-ol derivatives were examined, and structure–activity relationships were studied from the aspects of the stereochemistry of the oxirane ring, saturation, and substituent effects on the piperidine ring system.",10.1055/s-0040-1719887,2022-03-23,0.584526897302225
Synlett,A Carbohydrate-Based Approach for the Total Synthesis of Xyolide,"We have achieved a total synthesis of xyolide, a bioactive nonenolide, by following a carbohydrate-based approach starting from d -(–)-ribose. The key reactions involved epoxide opening with a long-chain aliphatic Grignard reagent, Yamaguchi esterification, and a ring-closing-metathesis reaction. The longest linear sequence was nine steps and the overall yield was 30%.",10.1055/s-0033-1339896,2013-10-28,0.58452538046129
Synthesis,Synthesis of C-Nor-D-homo-steroidal Alkaloids and Their Derivatives,"The C-nor-D-homo-steroidal alkaloid cyclopamine was discovered in the 1969 and in 2000 it was shown to act as an inhibitor of the hedgehog signaling (Hh) pathway, which is aberrantly activated in some tumors. Subsequently it was revealed that this natural occurring alkaloid has also antidiabetic and antiviral properties. In this review we present syntheses of selected C-nor-D-homo-steroidal alkaloids and their analogues and also discuss a general access to C-nor-D-homo-steroids. Some historical as well as biomedical aspects are also presented. 1 Introduction 2 Total Synthesis of Cyclopamine 2.1 Synthesis of exo-Cyclopamine and Further Cyclopamine Analogues 2.2 Synthesis of a Carbacyclopamine Analogue 3 D-Homocyclopamine: Saridegib (IPI-926) 4 Synthesis of Nakiterpiosin 5 Lewis Acid Mediated Nazarov Cyclization as a Versatile Method for C-Nor-D-homo-steroid Synthesis 6 Conclusion",10.1055/s-0036-1591965,2018-03-21,0.5845248041417456
Tetrahedron,A new pyridine synthesis and its redirection to a pyrrole synthesis with cuprous chloride,,10.1016/s0040-4039(01)94079-1,1972-01-01,0.5845232943441708
Green Chemistry,Eco-friendly synthesis of pyridines via rhodium-catalyzed cyclization of diynes with oximes,"We describe a new route for the synthesis of pyridines <italic>via</italic> [2 + 2 + 2] cycloaddition of diynes and oximes catalyzed by Rh(NBD) <sub>2</sub> BF <sub>4</sub> /MeO-Biphep using ethanol as an alternative reaction medium, affording the desired pyridine derivatives in yields of up to 93%.",10.1039/c4gc01756k,2014-11-03,0.5845056798698879
Synlett,Short and Efficient Synthesis of Diazabicycloalkane Dipeptide Mimics,A new synthetic route to enantiomerically pure diazabicycloalkanes is reported. Key step of this synthesis is an oxidative cleavage of azabicycloalkene precursors that are synthesized in enantiomerically pure form via aza-Diels-Alder reaction. A range of diazabicycloalkanes with different amino acid side chains have been synthesized and their structure has been elucidated by NMR analysis.,10.1055/s-2002-34901,2002-01-01,0.584503399964038
Journal of Organic Chemistry,Total Synthesis and Structural Revision of Hericerin,"The total synthesis of hericerin, a pollen growth inhibitor from Hericium erinaceum, was achieved. We found that the reported structure of hericerin should be revised to be the carbonyl regioisomer.",10.1021/jo300719m,2012-06-06,0.5844999838160633
Journal of Organic Chemistry,Synthesis of Both Possible Isomers of the Northwest Quadrant of Altromycin B,"The synthesis of the northwest quadrant of Altromycin B is described. The preparation of the two epimers at the quaternary carbon of the 6-deoxy-C-altrose moiety in the northwest quadrant is accomplished starting from d-glucose. A key step of our synthetic sequence is the formation of the C-glycoside linkage via the Ramberg-Bäcklund reaction. Two different routes are explored, which differ mainly on the timing of the conversion of glucose to altrose, either before or after the preparation of the C-glycoside. The conformation behavior of variously substituted C-altropyranoside rings is also discussed.",10.1021/jo034607k,2003-09-19,0.5844989516847134
Tetrahedron,Differentiation of diols; A new synthesis of bromoformates and protected hydroxyaldehydes,,10.1016/s0040-4039(01)82367-4,1974-01-01,0.584496853601657
Journal of the American Chemical Society,Small Molecule Inhibitors of Bacterial Quorum Sensing and Biofilm Formation,"Bacteria monitor their local population densities using small molecules (or autoinducers) in a process known as quorum sensing. Here, we report a new and efficient synthetic route to naturally occurring bacterial autoinducers [N-acyl l-homoserine lactones (AHLs)] that is readily amenable to the synthesis of analogues. This route has been applied in the first synthesis of a library of non-native AHLs. Evaluation of these compounds in bacterial reporter gene and biofilm assays has revealed a potent set of quorum sensing antagonists. These ligands will serve as valuable new tools to explore the role of quorum sensing in bacterial pathogenesis.",10.1021/ja0530321,2005-08-26,0.5844965846568847
Journal of Organic Chemistry,Short Enantioselective Total Syntheses of <i>trans</i>-Clerodane Diterpenoids: Convergent Fragment Coupling Using a <i>trans</i>-Decalin Tertiary Radical Generated from a Tertiary Alcohol Precursor,"The evolution of a convergent fragment-coupling strategy for the enantioselective total synthesis of trans-clerodane diterpenoids is described. The key bond construction is accomplished by 1,6-addition of a trans-decalin tertiary radical with 4-vinylfuran-2-one. The tertiary radical is optimally generated from the hemioxalate salt of the corresponding tertiary alcohol upon activation by visible light and an Ir(III) photoredox catalyst. The enantioselective total synthesis of trans-clerodane diterpenoid 1 reported here was accomplished in seven steps from 3-methyl-2-cyclohexenone. The synthetic strategy described in this report allows a number of trans-clerodane diterpenoids to be synthesized in enantioselective fashion by synthetic sequences of 10 steps or less. This study illustrates a powerful tactic in organic synthesis in which a structurally complex target structure is disconnected at a quaternary carbon stereocenter to fragments of comparable complexity, which are united in the synthetic pathway by conjugate addition of a nucleophilic tertiary radical to a fragment harboring an electron-deficient C-C double bond.",10.1021/acs.joc.6b00697,2016-06-02,0.584493867016046
Synlett,"A Short and Efficient Synthesis of (-)-4a,5-Dihydrostreptazolin","All articles of this category (-)-4a,5-Dihydrostreptazolin has been synthesized in 9 steps from d-glyceraldehyde acetonide. Key steps include a diastereoselective addition of a vinylic Grignard reagent onto an imine, a ring-closing metathesis and a highly stereoselective enyne radical-mediated cyclization. (-)-4a,5-dihydrostreptazolin - total synthesis - ring-closing metathesis - radical cyclization - d-glyceraldehyde acetonide",10.1055/s-2000-6433,2000-01-01,0.5844847844684957
Organic Letters,"[5C + 1N] Annulations: Two Novel Routes to Substituted Dihydrofuro[3,2-<i>c</i>]pyridines","Two novel routes based on [5C + 1N] annulations for the synthesis of 2,3-dihydrofuro[3,2-c]pyridines are described. Ammonium acetate (NH(4)OAc) is used as an ammonia source in both routes. The first route utilizes 1-acyl-1-[(dimethylamino)alkenoyl]cyclopropanes as a five-carbon 1,5-bielectrophilic species and combines the [5C + 1N] annulation and regioselective ring-enlargement of cyclopropyl ketone into one pot, whereas the second route utilizes 3-acyl-2-[(dimethylamino)alkenyl]-4,5-dihydrofurans as the five-carbon synthons, which involves a sequential intermolecular aza-addition, intramolecular aza-nucleophilic addition/elimination, and dehydration reaction.",10.1021/ol302314c,2012-10-01,0.5844842968890117
Synlett,"Preparation of the Three C1-C7, C8-C15, and C16-N22 Fragments of the Hsp90 Inhibitor Herbimycin A",International audience,10.1055/s-2005-864804,2005-03-23,0.5844818698859238
Journal of Organic Chemistry,Concise Synthesis of the CDE Ring System of Tetrahydroisoquinoline Alkaloids Using Carbophilic Lewis Acid-Catalyzed Hydroamidation and Oxidative Friedel−Crafts Cyclization,"A concise synthesis of the CDE ring system of the tetrahydroisoquinoline antitumor alkaloids such as saframycins, renieramycins, and ecteinascidins has been developed. Both Au(I)-catalyzed intramolecular hydroamidation of alkynylamide and NBS-mediated oxidative Friedel-Crafts cyclization of the resulting 2-ketopiperazine were utilized as key reactions.",10.1021/jo800898k,2008-06-05,0.5844747309805317
European Journal of Organic Chemistry,Synthesis of 2‐Substituted Indoles by Pd‐Catalyzed Reductive Cyclization of 1‐Halo‐2‐nitrobenzene with Alkynes,"Abstract An effective process for synthesizing 2‐substituted indoles in a one‐pot tandem reaction of 1‐halo‐2‐nitrobenzene and terminal alkynes through addition/reductive cyclization is presented. This protocol involves a Sonogashira‐type coupling reaction followed by reductive cyclization employing dppf (1,1′‐bis(diphenylphosphino)ferrocene) ligated Pd dithiolate complex as a catalyst and Zn as an inexpensive reductant. This efficient and tandem process tolerates broad functional groups with moderate to good yields. The gram‐scale synthesis of 2‐substituted indole has also been demonstrated. This protocol provides an alternative route for the synthesis of 2‐substituted indoles.",10.1002/ejoc.202101505,2022-01-11,0.5844696651605698
Organic Letters,A Novel and Efficient Total Synthesis of Cephalotaxine,"Total synthesis of cephalotaxine (CET), the parent member of a class of structurally unique antileukemia &lt;i&gt;Cephalotaxus&lt;/i&gt; alkaloids, was\naccomplished on the basis of a conceptually novel strategy featuring transannular reductive skeletal rearrangements as the key transformations\nfor the construction of the pentacyclic ring skeleton of CET. The synthetic potential of the designated Clemmensen−Clemo−Prelog−Leonard\nreductive rearrangement was demonstrated for the first time in a facile synthesis of the benzazepine subunit of CET. A novel endocyclic\nenamine (cyclopentenone) annulation was discovered and rationalized as an unusual azo-Nazarov-type cyclization.",10.1021/ol900496t,2009-03-16,0.5844683037858709
Journal of the American Chemical Society,"Cobalt-Mediated, Enantioselective Synthesis of <i>C</i><sub>2</sub> and <i>C</i><sub>1</sub> Dienes","The asymmetric C-H functionalization of norbornene and norbornadiene with five-, six-, and seven-membered cyclic enones mediated by the reactive intermediate [{η(5)-((t)BuMe(2)Si)C(5)H(4)}Co(NO)(2)] is reported. A novel base mixture derived from enantiopure ammonium salts and NaHMDS was used as a source of chirality, and this enantioselective desymmetrization of C(s) alkenes has been applied to the asymmetric synthesis of C(2)- and C(1)-symmetric diene ligands in high regioselectivity (3.7-20:1 anti/syn), near perfect diastereoselectivity (>99:1 dr), and high enantioselectivity (90-96% ee).",10.1021/ja107968c,2010-10-29,0.5844666089848879
Tetrahedron,"Chitosan catalyzed an efficient, one pot synthesis of pyridine derivatives",,10.1016/j.tetlet.2015.02.111,2015-02-26,0.5844582869030422
European Journal of Organic Chemistry,Total Synthesis of the Indolizidinium Alkaloid Ficuseptine,"The first total synthesis of ficuseptine [4,6-bis(4-methoxyphenyl)-1,2,3-trihydroindolizidinium chloride] (1), an alkaloid from Ficus septica, is described. The crucial steps in this five-step synthesis are a palladium-catalyzed bis(arylation) of a dibromopyridine under Suzuki conditions and a palladium-catalyzed alkynylation of an iodopyridine under Sonogashira conditions, as well as a novel Sandmeyer-type iodination of a 2-aminopyridine derivative. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)",10.1002/1099-0690(200207)2002:14<2288::aid-ejoc2288>3.0.co;2-g,2002-07-01,0.584442749770904
Tetrahedron,New synthetic route to diaminonitropyrazoles as precursors of energetic materials,,10.1016/s0040-4039(03)01301-7,2003-07-01,0.5844339887960024
European Journal of Organic Chemistry,Enantio‐ and Diastereoselective Syntheses of 3‐Hydroxypiperidines through Iridium‐Catalyzed Allylic Substitution,"Abstract Stereoselective syntheses of 3‐hydroxypiperidines have been developed. Key intermediates are N ‐protected allylamines that are prepared by an enantioselective iridium‐catalyzed allylic amination. A subsequent catch and release procedure that involves an epoxidation and base‐mediated elimination yields δ‐lactams that are suitably functionalized to prepare biologically active 3‐hydroxypiperidines. In addition, applications of this method to the total syntheses of deoxymannojirimycin, D ‐ erythro ‐sphingosine, and chiral building blocks of interest for medicinal chemistry are described.",10.1002/ejoc.201300445,2013-07-02,0.5844334347600714
European Journal of Organic Chemistry,Two‐Step Synthesis of Blue Luminescent (Pyrrol‐3‐yl)‐1<i>H</i>‐(aza)indazoles Based on a Three‐Component Coupling–Cyclocondensation Sequence,"Abstract (Pyrrol‐3‐yl)‐1 H ‐(aza)indazoles can be efficiently prepared by a two‐step process that consists of a consecutive three‐component coupling–cyclocondensation synthesis to give ortho ‐halo‐3‐acylpyrrol‐3‐yl‐substituted (hetero)arenes followed by a cyclization–condensation–S N Ar sequence. Almost all derivatives display an intense blue emission upon excitation in the near UV with enormous Stokes shifts (6500–8300 cm –1 ) and considerable high fluorescence quantum yields ( Φ f = 0.28–0.46). Electronic transitions can be plausibly rationalized by TD‐DFT computations performed on DFT‐optimized geometries. Reversible protonation leads to static fluorescence quenching in narrow pH‐ranges, which qualifies the title compounds as favorable ON/OFF fluorescence switching systems.",10.1002/ejoc.201500575,2015-07-08,0.5844235902629998
Organic Process Research & Development,The Effect of Water and Phenol on the Chiral Oxazaborolidine-Catalyzed Reduction of a Prostaglandin Enone Derivative,"The alcohol 2, a key intermediate in the synthesis of the highly selective EP4-receptor agonist ONO-4819, was synthesized by ( R )-methyloxazaborolidine (( R )-Me-CBS)-catalyzed asymmetric reduction of enone 1 with borane dimethylsulfide complex. Addition of water and phenol to the reduction of enone 1 using ( R )-Me-CBS as catalyst changed the chemoselectivity of the reduction.",10.1021/op900118n,2009-07-13,0.5844221766795579
Tetrahedron,A short route to multiply substituted fluorenones,,10.1016/s0040-4039(99)00370-6,1999-04-01,0.5844210946028828
Angewandte Chemie International Edition,Enantioselective Synthesis of (−)‐β‐Santalol by a Copper‐Catalyzed Enynol Cyclization–Fragmentation Reaction,"The right cat for the desired odor: The key step in an enantioselective synthesis of the prized fragrance (−)-β-santalol was a highly selective copper-catalyzed cyclization–fragmentation reaction of an enynol (see scheme). When a platinum catalyst was used for the cyclization step, the desired fragmentation did not take place; instead, a product containing a cyclopropane ring was formed with 100 % selectivity.",10.1002/anie.200903449,2009-08-24,0.5844147581410627
Angewandte Chemie International Edition,Stereoselective Total Synthesis of the Ionophore Antibiotic Zincophorin,"Acyclic stereocontrol is the basis of an original strategy adopted for the first, highly stereoselective total synthesis of the free acid zincophorin (1), a unique ionophore antibiotic. The stereoselective synthesis of the trisubstituted tetrahydropyran moiety and the construction of the eight contiguous stereogenic centers were key challenges in the synthesis.",10.1002/anie.200460434,2004-08-13,0.5844134552658905
Synlett,An Efficient Access to Aspermytin A and Oblongolide C through an Intramolecular Nitrile Oxide–Alkene [3+2] Cycloaddition,The second generation synthesis of (+)-aspermytin A and the first total synthesis of (–)-oblongolide C have been accomplished employing an intramolecular nitrile oxide–alkene [3+2] cycloaddition as the key step.,10.1055/s-0032-1317693,2012-12-04,0.5844130231819488
Organic Letters,Synthesis of Enantiomerically Pure Pyrimidine Ribonucleosides Locked in the South Conformation,"The conformation of the central five-membered ring of a nucleoside plays an important role in enzyme recognition. Bicyclo[3.1.0]hexane, also known as the methanocarba (MC), serves as a template that can mimic the locked forms of the two distinctive conformations, namely, the north and south conformations. While modified nucleosides locked in the north conformation have been actively investigated, the south counterpart remains largely unexplored because it is difficult to synthesize. Herein, we report a concise synthetic route that can provide the key amino sugar intermediate essential for the synthesis of ( S )-MC ribonucleosides in a 100% stereoselective manner. Also, through the proposed synthetic approach, we report the first synthesis of enantiomerically pure ( S )-MC cytidine 1 . We believe our findings would greatly contribute to the field of nucleoside chemistry and provide opportunities for novel nucleoside discovery.",10.1021/acs.orglett.2c03853,2022-12-13,0.584408098500376
Tetrahedron,"Total synthesis of the germacranolide (±)-aristolactone via [2,3] wittig ring contraction",,10.1016/s0040-4039(01)80972-2,1987-01-01,0.5844007740699083
Organic Letters,"Modular Total Syntheses of the Alkaloids Discoipyrroles A and B, Potent Inhibitors of the DDR2 Signaling Pathway","The title natural product 1 has been synthesized by treating the 1,2,3,5-tetrasubstituted pyrrole 23 with oxoperoxymolybdenum(pyridine) (hexamethylphosphoric triamide) (MoOPH). Compound 23 was itself prepared in seven steps from parent pyrrole using Ullmann-Goldberg and Suzuki-Miyaura cross-coupling, Vilsmeier-Haack formylation, electrophilic bromination, and Wittig olefination reactions as key steps. Related chemistry has been used to prepare discoipyrrole B (2).",10.1021/acs.orglett.5b03672,2016-02-02,0.5844001343683841
Tetrahedron,Synthesis of new halo-containing acetylenes and their application to the synthesis of azoles,,10.1016/s0040-4039(04)00897-4,2004-05-01,0.5843996783234962
Tetrahedron,Synthesis of new halo-containing acetylenes and their application to the synthesis of azoles,,10.1016/j.tetlet.2004.04.106,2004-05-29,0.5843996783234962
Journal of Organic Chemistry,Total Synthesis and Structural Revision of Greensporone F and Dechlorogreensporone F,"The first asymmetric total syntheses of the real isolation product (2 S,5 R,8 R )-greensporone F and (2 S,5 R,8 R )-dechlorogreensporone F, 14-membered resorcylic acid lactones with a cis -2,5-disubstituted tetrahydrofuran ring system, was accomplished. The synthesis features a late-stage Lewis acid-catalyzed stereoselective intramolecular oxa-Michael reaction, E -selective ring-closing metathesis, De Brabander’s esterification, and Jacobsen’s hydrolytic kinetic resolution as the key steps. Synthesis of both real isolation and erroneously proposed structure necessitated the revision of the absolute configuration of greensporone F and dechlorogreensporone F. The erroneous representation of (2 S,5 S,8 S )-configuration in greensporone F and dechlorogreensporone F was assigned to be (2 S,5 R,8 R ) by comparison with the NMR data and specific rotation of the synthetic compounds with that of the reported data.",10.1021/acs.joc.0c01644,2020-09-02,0.5843988286208924
Organic Process Research & Development,Process Development of Febuxostat Using Palladium- and Copper-Catalyzed C–H Arylation,"There is significant interest in the development of process routes for active pharmaceutical ingredients using C–H arylation methodology. An efficient and practical synthetic route for febuxostat ( 1 ), which is the first non-purine-type xanthine oxidase inhibitor, was established via palladium- and copper-catalyzed C–H arylation of thiazole with aryl bromide. The catalyst loading was reduced to 0.1 mol % for the intermolecular C–H arylation, and a three-step synthesis produced febuxostat in 89% overall yield with excellent selectivity.",10.1021/acs.oprd.8b00164,2018-09-07,0.5843959840596754
Organic Letters,Convergent Synthesis and Biological Activity of the WXYZA′B′C′ Ring System of Maitotoxin,"The WXYZA'B'C' ring system ( 1) of maitotoxin (MTX) was synthesized in a convergent manner via successive coupling of the W, Z, and C' ring fragments through construction of the XY and A'B' ring systems. The synthetic segment 1 blocked the hemolytic activity elicited by MTX.",10.1021/ol801369g,2008-07-23,0.5843958774150452
Organic Letters,"Enantioselective Synthesis of the [6,6] Spiroketal Core of Reveromycin A","[structure: see text] Reveromycin A (1) belongs to a family of microbial polyketides with unusual structural features and biological activities. The structure of 1 is composed of a [6,6] spiroketal core decorated with highly unsaturated side chains. As a prelude to the synthesis of 1, we present herein a short, efficient, and enantioselective synthesis of the C9-C21 fragment 5 (spiroketal core) of reveromycin A.",10.1021/ol991290v,1999-12-17,0.5843945510611994
Journal of Organic Chemistry,Total Synthesis of Batatoside L,"The total synthesis of batatoside L (1), a resin glycoside possessing cytotoxicity against laryngeal carcinoma cells, has been completed in a highly convergent manner. The most crucial step in this total synthesis was the efficient construction of the 18-membered macrolactone framework through the Corey-Nicolaou macrolactonization approach.",10.1021/jo101231r,2010-07-28,0.5843808406978527
Synlett,Expedient Synthetic Transformation of Ptychantins into Forskolin,"Forskolin has been synthesized in 11 steps with a 17% overall yield from ptychantins A and B, which have been isolated from the liverwort Ptychanthus striatus in good yield. The 1α-hydroxy group was furnished by stereoselective reduction of the corresponding carbonyl group by sodium cyanoborohydride. The 9α-hydroxy group was introduced stereoselectively by epoxidation of Δ9,11-enol ether.",10.1055/s-2008-1042930,2008-03-20,0.584376560124322
Journal of Organic Chemistry,Total Synthesis of the Lycopodium Alkaloid Serratezomine A Using Free Radical-Mediated Vinyl Amination to Prepare a β-Stannyl Enamine Linchpin,"Serratezomine A is a member of the structurally diverse class of compounds known as the Lycopodium alkaloids. The key supporting studies and successful total synthesis of serratezomine A are described in this account. Significant features of the synthesis include the first application of free radical mediated vinyl amination and Hwu's oxidative allylation in a total synthesis and an intramolecular lactonization via a transannular S(N)i reaction. Minimal use of protecting groups and the highly diastereoselective formation of a hindered, quaternary stereocenter using an umpolung allylation are also highlights from a strategy perspective. Observation of quaternary carbon epimerization via a retro-Mannich/Mannich sequence highlights the additional challenge presented by the axial alcohol at C8 in serratezomine A.",10.1021/jo302333s,2012-12-28,0.5843755197210041
Journal of Organic Chemistry,Enantioselective Syntheses of Morpholines and Their Homologues via S<sub>N</sub>2-Type Ring Opening of Aziridines and Azetidines with Haloalcohols,A highly regio- and stereoselective strategy for the syntheses in high yield and enantioselectivity of a variety of substituted nonracemic morpholines and their homologues is described. The reaction proceeds via an S(N)2-type ring opening of activated aziridines and azetidines by suitable halogenated alcohols in the presence of Lewis acid followed by base-mediated intramolecular ring closure of the resulting haloalkoxy amine.,10.1021/jo901297d,2009-08-12,0.5843732743046929
Tetrahedron,Spongistatin synthetic studies. 3. Construction of the C(1–17) spiroketal,"A convergent synthesis of the C(1–17) AB-ring subunit of the spongistatins, exceedingly scarce and highly antimitotic polyether macrolides, has been achieved via a one-flask dithiane bisalkylation, stereocontrolled spiroketalization, and Julia sulfone coupling/methylenation.",10.1016/s0040-4039(97)10501-9,1997-12-01,0.5843692714165142
Tetrahedron,Synthesis of an advanced quinocarcin intermediate from 1-glutamic acid,,10.1016/0040-4039(90)80083-x,1990-01-01,0.5843557454389932
Journal of Organic Chemistry,"Expedient Synthesis of <i>threo</i>-β-Hydroxy-α-amino Acid Derivatives:  Phenylalanine, Tyrosine, Histidine, and Tryptophan","An expedient synthesis of enantiomerically pure threo-beta-hydroxy-alpha-amino acid derivatives of phenylalanine, tyrosine, histidine, and tryptophan is described. The NBS-mediated radical bromination of the N,N-di-tert-butoxycarbonyl protected alpha-amino acids and subsequent treatment with silver nitrate in acetone provided the trans-oxazolidinones predominantly. Cesium carbonate catalyzed hydrolysis then generated the beta-hydroxy amino acid derivatives in excellent overall yield.",10.1021/jo061159i,2006-08-08,0.5843556535023756
Tetrahedron,"Utilization of L-serine in an oxime olefin cycloaddition route to a functionalized asymmetric pyrrolidine, a selective α-glucosidase inhibitor",,10.1016/0040-4039(94)85229-4,1994-04-01,0.5843530091708837
Journal of the American Chemical Society,Studies for the Synthesis of Xenicane Diterpenes. A Stereocontrolled Total Synthesis of 4-Hydroxydictyolactone,"The stereocontrolled total synthesis of 4-hydroxydictyolactone (4), a member of the xenicane diterpene family of natural products, is described. These studies feature the development of the B-alkyl Suzuki cross-coupling reaction for direct access to (E)-cyclononenes from acyclic precursors. The Ireland-Claisen rearrangement is effectively utilized to establish the backbone asymmetry of the contiguous C(2), C(3), C(10) stereotriad of 4. The synthesis strategy has devised an intramolecular Nozaki-Hiyama reductive allylation of a formate ester for the stereoselective formation of five-membered lactols 22. In addition, an internally directed S(E)' propargylation using allenylmagnesium bromide is described to establish the stereochemistry of the C(4) alcohol in 27, and the terminal alkyne is subsequently functionalized via a regioselective syn-silylstannylation to yield 30. Finally, the stereocontrolled phenylselenylation of the ester enolate derived from 43 leads to the desired syn-oxidative elimination to yield the natural product 4.",10.1021/ja902677t,2009-06-01,0.5843489578996182
Angewandte Chemie International Edition,Enantioselective Total Synthesis of (–)‐Psiguadial A,"The first enantioselective total synthesis of the antiproliferative natural product (-)-psiguadial A is reported. This approach features the enantioselective synthesis of a complex tricyclic terpenoid precursor, the union of that precursor with a polyketide component by an enolate-ortho-quinone methide coupling reaction to form a highly congested carbon─carbon bond, and an acid-mediated intramolecular hydration ring-closure leveraging a fully substituted alkene to generate the unique oxepane core structure of the natural product.",10.1002/anie.202506537,2025-05-20,0.5843465234852534
Tetrahedron,Synthetic studies towards the group A streptogramin antibiotics. Synthesis of the C9–C23 fragment,,10.1016/s0040-4039(01)00973-x,2001-07-01,0.5843462993753339
Tetrahedron,Synthesis of chiral building blocks for selective adenosine receptor agents. Lipase-catalyzed resolution of 2-benzylpropanol and 2-benzylpropionic acid.,,10.1016/s0040-4039(00)97174-0,1990-01-01,0.5843417891150757
Chemical Science,Efficient synthesis of antiviral agent uprifosbuvir enabled by new synthetic methods,/TMDSO; (4) dynamic stereoselective phosphoramidation using a chiral nucleophilic catalyst. The new route improves the yield of uprifosbuvir 50-fold over the previous manufacturing process and expands the tool set available for synthesis of antiviral nucleotides.,10.1039/d1sc01978c,2021-01-01,0.5843406333401711
Tetrahedron,A simple and efficient one-step synthesis of 3-substituted-4-hydroxyquinolin-2-one derivatives,,10.1016/j.tetlet.2012.01.140,2012-02-08,0.5843320710269927
Organic Letters,Synthesis of Xanthones via Copper(II)-Catalyzed Dehydrogenative Cyclization and Successive Aromatization in a One-Step Sequence,"In this study, an unprecedented approach to the xanthone scaffold from cyclohexyl(2-hydroxyphenyl)methanone via dehydrogenative cyclization and a successive aromatization cascade is reported. This methodology affords a novel route to the privileged structure with a wide substrate scope (a total of 29 compounds, ≤96% yield) in a highly atom-economic manner.",10.1021/acs.orglett.2c03730,2022-12-13,0.5843311958931944
Journal of the American Chemical Society,Total Synthesis of Dictyodendrin B,"A concise total synthesis of dictyodendrin B (1) is reported, a scarce marine alkaloid endowed with promising telomerase inhibitory activity. Key steps of the chosen route are a reductive cyclization of ketoamide 11 to indole 12 mediated by low-valent titanium (from TiCl3 and KC8) followed by a photochemical 6pi-electrocyclization, which was performed in the presence of Pd/C and nitrobenzene to effect concomitant dehydrogenation/aromatization of the product initially formed. Regioselective bromination of the resulting pyrrolocarbazole 13 followed by lithium/bromine exchange and quenching of the resulting organolithium species with p-methoxybenzaldehyde installed the side chain at C2. Oxidation of the benzylic alcohol 15 thus obtained to ketone 17 was best achieved with catalytic amounts of tetra-n-propylammonium perruthenate (TPAP) and N-methylmorpholine-N-oxide (NMO) in dilute CH2Cl2 solution to avoid the formation of undue amounts of the unsymmetrical dimer 16. Ketone 17 was elaborated into the natural product by selective cleavage of the isopropyl ether with BCl3, introduction of the sulfate moiety with the aid of trichloroethyl chlorosulfuric acid ester, deprotection of all lateral methyl ether groups, and final reductive cleavage of the trichloroethyl ester moiety. The spectroscopic data of synthetic dictyodendrin B thus formed matched those of an authentic sample in all regards. Moreover, it was shown that global deprotection of the peripheral -OH groups in pyrrolo[2,3-c]carbazole 13 is accompanied by spontaneous air-oxidation to form the quinone core of dictyodendrin C.",10.1021/ja0541175,2005-07-29,0.5843311844623715
Tetrahedron,Highly selective fluorescent sensing of Pb2+ by a new calix[4]arene derivative,,10.1016/j.tetlet.2006.01.075,2006-02-04,0.5843246712734468
Tetrahedron,Studies toward the synthesis of Stemona alkaloids; a short synthesis of the tricyclic core of tuberostemonines,,10.1016/0040-4039(95)02302-x,1996-02-01,0.584313909139324
European Journal of Organic Chemistry,Protecting Group Free Formal Total Synthesis of the Antitubercular Agent Erogorgiaene,"In the original article,1 the number of steps involved in the formal total synthesis of erogorgiaene was erroneously reported. The total number of steps for this formal total synthesis should be 13. In addition, ref.4a,8a,8b were cited incorrectly. The correct citations are given below. Moreover, the synthesis of 9 should be cited as ref.6b The Authors",10.1002/ejoc.201200142,2012-02-23,0.5843135515061036
Organic Letters,A Concise Enantioselective Synthesis of Fluorinated Pyrazolo-Piperidine GSK3901383A Enabled by an Organocatalytic Aza-Michael Addition,"A highly enantioselective organocatalytic aza-Michael addition of 4-nitro-pyrazole to ethyl ( E )-2,2-difluoro-5-oxopent-3-enoate has been developed. This reaction enabled a concise, four-step, stereoselective synthesis of highly functionalized 3,3-difluoro-4-pyrazolo-piperidine GSK3901383A, a key intermediate for the synthesis of a leucine-rich repeat kinase 2 inhibitor API. Computational analysis provided insight into the steric requirements of the catalytic system, enabling rational selection of a highly selective catalyst.",10.1021/acs.orglett.3c03694,2024-02-16,0.5843127804137452
Tetrahedron,"A novel method for the preparation of N,N′-disubstituted-N′′-nitroguanidines, including a practical synthesis of the neonicotinoid insecticide clothianidin",,10.1016/s0040-4039(00)01225-9,2000-09-01,0.5843041842230565
Journal of the American Chemical Society,Asymmetric Total Synthesis of Illisimonin A,"High Resolution Image Download MS PowerPoint Slide The discovery of illisimonin A in 2017 extended the structural repertoire of the Illicium sesquiterpenoids─a class of natural products known for their high oxidation levels and neurotrophic properties─with a new carbon backbone combining the strained trans -pentalene and norbornane substructures. We report an asymmetric total synthesis of (−)-illisimonin A that traces its tricyclic carbon framework back to a spirocyclic precursor, generated by a tandem-Nazarov/ene cyclization. As crucial link between the spirocyclic key intermediate and illisimonin A, a novel approach for the synthesis of tricyclo[5.2.1.0 1,5 ]decanes via radical cyclization was explored. This approach was applied in a two-stage strategy consisting of Ti(III)-mediated cyclization and semipinacol rearrangement to access the natural product’s carbon backbone. These key steps were combined with carefully orchestrated C–H oxidations to establish the dense oxidation pattern.",10.1021/jacs.3c01262,2023-03-16,0.5842960657367994
Journal of the American Chemical Society,"Asymmetric Synthesis of Unsaturated, Fused Bicyclic Proline Analogues through Amino Alkylation of Cyclic Bis(allylsulfoximine)titanium Complexes and Migratory Cyclization of δ-Amino Alkenyl Aminosulfoxonium Salts","Described is an asymmetric synthesis of new Delta(3a,4)-unsaturated, fused bicyclic proline analogues from cyclic bis(allylsulfoximine)titanium complexes and N-tert-butylsulfonyl imino ethyl ester. Treatment of the enantiomerically pure five-, six-, seven-, and eight-membered cyclic bis(allylsulfoximine)titanium complexes with the imino ester gave mixtures of the corresponding (E,syn)- and (Z,syn)-configured, delta-sulfoximine substituted, cyclic gamma,delta-unsaturated alpha-amino acid esters with high regio- and diastereoselectivities in good yields. Activation of the N-methyl sulfoximine group of these amino acid derivatives through methylation with Me(3)OBF(4) afforded in nearly quantitative yields the corresponding (dimethylamino)sulfoxonium salts. A novel migratory cyclization of these salts with DBU gave via an isomerization to the corresponding allylic (dimethylamino)sulfoxonium salts and an intramolecular substitution of the (dimethylamino)sulfoxonium group the enantio- and diastereomerically pure, bicyclic, N-tert-butylsulfonyl protected proline analogues having a six- and eight-membered unsaturated carbocyclic ring. Cyclization of the alkenyl (dimethylamino)sulfoxonium salts was independent of the configuration of the double bond. N,N-Dimethylphenylsulfinamide of > or =99% ee was obtained in good yield as a further reaction product. Conversion of the sulfinamide to N,S-dimethyl-S-phenylsulfoximine of > or =99% ee, the starting material for the synthesis of the allylic sulfoximines, had been accomplished previously. Finally, cleavage of the tert-butylsulfonyl protecting group with anhydrous acid furnished the fused bicyclic proline analogue containing an unsaturated six-membered ring in high yield.",10.1021/ja030324y,2003-10-01,0.5842914624977734
Synthesis,Practical and Scaleable Syntheses of 3-Hydroxythiophenol,3-Hydroxythiophenol is a versatile intermediate for the synthesis of medicinal and heterocyclic compounds. Two novel and practical syntheses of 3-hydroxythiophenol are achieved using readily available and inexpensive starting materials. An overall cost comparison of these syntheses is also given.,10.1055/s-2003-36251,2003-01-01,0.5842913548656825
Organic Letters,Concise Total Synthesis of (±)-Cephalotaxine via a Transannulation Strategy: Development of a Facile Reductive oxy-Nazarov Cyclization,"A concise total synthesis of (±)-cephalotaxine (1) has been achieved from dioxolanone derivative 15 via a transannulation strategy. The key transformation is a facile reductive oxy-Nazarov cyclization as illustrated above, involving presumably a tethered 1,2-oxidopentadienyl cation species 7a or 7b, which represents a new variant of the oxy-Nazarov cyclization and constitutes an effective, regio- and stereospecific 5-hydroxy cyclopentenone annulation protocol under mild hydride reduction conditions.",10.1021/ol201390r,2011-06-08,0.5842910159019824
Angewandte Chemie International Edition,Total Synthesis of Zephycarinatines via Photocatalytic Reductive Radical <i>ipso</i>‐Cyclization,"We report herein a nonbiomimetic strategy for the total synthesis of the plicamine-type alkaloids zephycarinatines C and D. The key feature of the synthesis is a stereoselective reductive radical ipso-cyclization using visible-light-mediated photoredox catalysis. This cyclization enabled the construction of a 6,6-spirocyclic core structure through the addition of a carbon-centered radical onto the aromatic ring. Biological evaluation of zephycarinatines and their derivatives revealed that the synthetic derivative with a keto group displays moderate inhibitory activity against LPS-induced NO production. This approach could offer future opportunities to expand the chemical diversity of plicamine-type alkaloids as well as providing useful intermediates for their syntheses.",10.1002/anie.202009399,2020-08-08,0.5842816550827604
Organic Letters,"DAST-Mediated Cyclization of α,α-Disubstituted-α-acylaminoketones: Efficient and Divergent Synthesis of Unprecedented Heterocycles","The design of a new potent nonsteroidal ecdysone agonist led to the discovery of a diethylaminosulfur trifluoride (DAST)-mediated cyclization of α,α-disubstituted-α-acylaminoketones. The resulting fluorooxazolines can be ring-opened or selectively substituted by a range of nucleophiles to provide in high yields a diverse array of unprecedented heterocyclic frameworks.",10.1021/ol102454e,2010-12-08,0.5842727164806787
Journal of Organic Chemistry,The Synthesis of Deoxyfusapyrone. 1. An Approach to the Pyrone Moiety,"An effective synthesis of the C1-C10 component of deoxyfusapyrone has been achieved that will allow for the synthesis of both the (R) and (S) form of the C-8 chiral center starting from optically pure (+)- and (-)-3,3-dimethyl-2-hydroxy-gammalactone (pantolactone).",10.1021/jo0204707,2002-10-11,0.5842716725681775
Journal of Organic Chemistry,Enantioselective Synthesis of 2-Substitued-Tetrahydroisoquinolin-1-yl Glycine Derivatives via Oxidative Cross-Dehydrogenative Coupling of Tertiary Amines and Chiral Nickel(II) Glycinate,The asymmetric synthesis of 2-substituted-tetrahydroisoquinolin-1-yl glycines was achieved by an oxidative cross-dehydrogenative coupling (CDC) reaction. This method for activation of the α-C-H bonds of amines with chiral nickel(II) glycinate using o-chloranil as the sole oxidant afforded highly diastereoselective coupling adducts. The decomposition of coupling adducts readily afforded 2-substituted-tetrahydroisoquinolin-1-yl glycine derivatives.,10.1021/jo401510b,2013-10-11,0.5842714265527389
Tetrahedron,A solid-phase synthetic route to substituted 7-azabenzimidazoles suitable for combinatorial library synthesis,,10.1016/s0040-4039(00)00859-5,2000-07-01,0.5842697131657828
Journal of Organic Chemistry,"Piperidine-Mediated [3 + 3] Cyclization of 2-Amino-4<i>H</i>-chromen-4-ones and 2-Benzylidenemalononitriles: To Access 2-Aminochromeno[2,3-<i>b</i>]pyridine Derivatives","Piperidine-mediated [3 + 3] cyclization of 2-amino-4 H -chromen-4-ones and substituted 2-benzylidenemalononitriles was developed for the synthesis of 2-amino-4-aryl-5 H -chromeno[2,3- b ]pyridin-5-one derivatives. This novel transformation provides a highly efficient and facile route to functionalized 5 H -chromeno[2,3- b ]pyridines from readily available substrates under mild reaction conditions.",10.1021/acs.joc.1c00797,2021-06-23,0.5842638437417503
European Journal of Organic Chemistry,Enantioselective Synthesis of (+)‐(<i>S</i>)‐Laudanosine and (–)‐(<i>S</i>)‐Xylopinine,"Abstract The study presents a new pathway for the enantioselective synthesis of benzylisoquinoline alkaloids. The key steps of the synthesis of (+)‐( S )‐laudanosine ( 1 ) and (–)‐( S )‐xylopinine ( 2 ) are a Sonogashira coupling that builds up the C1–C8a bond of the benzylisoquinoline skeleton, an intramolecular Ti‐catalyzed hydroamination of an alkyne, and a subsequent enantioselective imine reduction according to Noyori’s protocol. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2005)",10.1002/ejoc.200500095,2005-06-20,0.5842598621963501
Synlett,"4-(Arylsulfonyl)glycals in Synthesis. Cation-Mediated Synthesis of 2,6-Disubstituted Dihydropyrans",,10.1055/s-1999-2540,1999-01-01,0.5842478216135737
Tetrahedron,"Biomimetic synthesis and stereostructure of K-13, a novel inhibitor of angiotensin I converting enzyme",,10.1016/s0040-4039(00)95207-9,1989-01-01,0.58424574672079
Tetrahedron,Arylation of 1-tributylstannyl glycals catalyzed by palladium: A synthetic route to the basic skeleton of the papulacandins and chaetiacandin,,10.1016/s0040-4039(00)97832-8,1990-01-01,0.5842455413920237
Tetrahedron,Radical-chain desulfurisation of α-(alkylthiomethyl)acrylates with triphenylphosphine: a new route to α-alkylacrylates,,10.1016/s0040-4039(97)10587-1,1998-01-01,0.5842446060342484
Organic Letters,A Scalable and Regioselective Synthesis of 2-Difluoromethyl Pyridines from Commodity Chemicals,A scalable de novo synthesis of difluoromethyl pyridines from inexpensive materials is reported. The pyridyl subunit is built around the difluoromethyl group rather than a late stage introduction of this moiety. This user-friendly approach allows access to a diverse range of substitution patterns on all positions on the ring system and on the difluoromethyl group.,10.1021/ol500402e,2014-03-06,0.5842425109030397
Angewandte Chemie International Edition,"Short, Enantioselective Total Synthesis of Highly Oxidized Taxanes","In the realm of natural product chemistry, few isolates have risen to the level of fame justifiably accorded to Taxol (1) and its chemical siblings. This report describes the most concise route to date for accessing the highly oxidized members of this family. As representative members of taxanes containing five oxygen atoms, decinnamoyltaxinine E (2) and taxabaccatin III (3), have succumbed to enantioselective total synthesis for the first time in only 18 steps from a simple olefin starting material. The strategy holistically mimics nature's approach (two-phase synthesis) and features a carefully choreographed sequence of stereoselective oxidations and a remarkable redox-isomerization to set the key trans-diol present in 2 and 3. This work lays the critical groundwork necessary to access even higher oxidized taxanes such as 1 in a more practical fashion, thus empowering a medicinal chemistry campaign that is not wedded to semi-synthesis.",10.1002/anie.201602235,2016-05-30,0.5842400886221186
Angewandte Chemie International Edition,Tetravinylallene,"The first chemical synthesis of tetravinylallene (3,5-divinylhepta-1,3,4,6-tetraene) is reported. The final, key step of the synthesis involves a palladium-catalyzed, Negishi-type cross-coupling involving 1,5-transposition of a penta-2-en-4-yn-1-ol methanesulfonate. The unprecedented fundamental hydrocarbon is sufficiently stable to be purified by flash chromatography. A similar synthetic pathway grants access to the first substituted tetravinylallenes, which provide insights into the influence of substitution upon stability and reactivity. Tetravinylallenes are shown to break new ground in swift structural complexity creation, with three novel sequences reported.",10.1002/anie.201908496,2019-08-16,0.5842399612638781
Journal of Organic Chemistry,"Sequential 1,3-Dipolar Cycloadditions in the Synthesis of Bis-Isoxazolo Substituted Piperidinones","A strategy for the efficient synthesis of novel bis-isoxazolo substituted piperidinones has been developed. The protocol consists of the Michael addition of an unsaturated alkoxide to beta-nitrostyrene followed by an intramolecular nitrile oxide cycloaddition (INOC) or an intramolecular silyl nitronate olefin cycloaddition (ISOC) to give III. Grignard addition to this isoxazoline intermediate followed by DCC coupling of the resulting isoxazolidine with nitroacetic acid gave II, and a second intramolecular cycloaddition via 1,3-dipoles result in the formation of the targeted novel tetracycles (I). A solid-supported scavenger was employed to increase the efficiency and yield of the Michael addition step.",10.1021/jo991418m,1999-12-29,0.5842376260876924
Organic Letters,"Efficient Synthesis of Chiral 2,2′-Bipyrrolidines by an <i>anti</i>-Selective Alkene Diamination",The rapid and efficient construction of complex chiral bicyclic amines is possible using a novel alkene diamination reaction. Electrophilic iodinating agents promote the intramolecular anti-selective diamination of alkenes and allow the efficient synthesis of chiral amines such as trans-bipyrrolidines.,10.1021/ol302855z,2012-11-26,0.5842359470772305
Organic Letters,Modular Synthesis of Polycyclic Alkaloid Scaffolds via an Enantioselective Dearomative Cascade,"High Resolution Image Download MS PowerPoint Slide The polycyclic core of the akuammiline alkaloids can be synthesized from simple tryptamine and tryptophol derivatives via a Ag(I)-catalyzed enantioselective dearomative cyclization cascade sequence. The complex tetracyclic scaffolds are prepared via a rapid, versatile, three-step modular synthesis from simple commercially available indole derivatives in high yields and enantiomeric excess (up to 99% yield and >99% ee ).",10.1021/acs.orglett.0c00053,2020-01-15,0.5842307610968629
European Journal of Organic Chemistry,Diastereoselective Synthesis of Lincosamine Precursors,"Abstract The stereoselective syntheses of the four aminodiol precursors of the diastereomers of lincosamine are reported. The procedure is based on the initial two‐carbon elongationof 1,2;3,4‐di‐ O ‐isopropylidene‐α‐ D ‐galactohexodialdo‐1,5‐pyranose, followed by the stereocontrolled introduction of the amino group by nucleophilic amination. Two complementary approaches have been investigated and compared: The first one is the direct transformation of α‐chloroglycidic ester into β‐amino‐α‐keto ester. The second strategy is a three‐step synthesis that is based on the treatment of the β‐iodo‐α‐keto ester with dibenzylamine. Subsequent reduction of the β‐amino‐α‐keto ester provides the pure D ‐ erythro , L ‐ threo , L ‐ erythro , and D ‐ threo aminodiols after chromatographic purification. Further classical transformations afford the N ‐acetyl derivatives, which are key precursors of the lincosamine diastereomers.",10.1002/ejoc.201001740,2011-02-25,0.5842299795263473
Synlett,An Ireland-Claisen Rearrangement/Lactonisation Cascade as a Key Step in Studies Towards the Synthesis of (-)-Euonyminol:,Progress towards the asymmetric total synthesis of (-)-euonyminol is described with the focus on the installation of the ­oxygenation pattern on the lower rim of the molecule. An Ireland-Claisen rearrangement/lactonisation cascade has been developed and studies towards further elaboration have uncovered an intriguing tunable diastereoselective α-bromination of the resulting γ-lactone.,10.1055/s-0031-1289543,2011-10-19,0.5842298855052543
Organic Process Research & Development,A Practical Preparation of Ethyl<i>N</i>-Acyl-2-(dimethoxyphosphoryl)glycinate,"A practical, cost-effective preparation of ethyl N -acyl-2-(dimethoxyphosphoryl)glycinate has been developed. The two-step process achieved an 80% overall isolated yield.",10.1021/op1000594,2010-04-29,0.5842278679065879
Tetrahedron,Synthesis of chiral [5]helicenes using aromatic oxy-Cope rearrangement as a key step,,10.1016/s0040-4039(03)00150-3,2003-03-01,0.5842251814401282
Journal of Organic Chemistry,Facile Preparation of Protected Furanoid Glycals from Thymidine,The synthesis of O -silyl- and O -acyl-protected furanose glycals from free thymidine was investigated. The method of glycal formation reported by Pedersen et al. was successfully expanded to include 5-ester (toluoyl) protected glycals as well as various combinations of 5‘-ester and 3- and 5- tert -butyldimethylsilyl and tert -butyldiphenylsilyl protection. Gram quantities of furanoid glycals can be prepared in a few days in two−four synthetic steps in overall yields ranging from 17 to 80%.,10.1021/jo970947s,1997-12-01,0.5842227944921188
Chemical Science,Synthesis of NiO nanoparticles for new nanocomposite materials,,,2016-06-29,0.5842109746059049
Organic Letters,A New Synthesis of Pentafluorosulfanylbenzene,"[reaction: see text] A new and convenient three-step synthesis of pentafluorosulfanylbenzene from 1,4-cyclohexadiene with an overall yield of >70% is reported along with a number of derivatization reactions.",10.1021/ol0491991,2004-06-08,0.5842041240062397
Tetrahedron,"Selective synthesis of 2-chloro-2,3-epoxy-2-oxazolines and isomeric 3-chloro-2-oxo-2-oxazolines",,10.1016/s0040-4039(00)71225-1,1991-01-01,0.5842040174311413
Tetrahedron,"Total synthesis of (−)-2-epi-lentiginosine by use of chiral 5-hydroxy-1,5-dihydropyrrol-2-one as a building block",,10.1016/j.tetlet.2007.10.125,2007-11-20,0.5842017330805785
Journal of Organic Chemistry,Total Synthesis of Phenanthroquinolizidine Alkaloids Using a Building Block Strategy,"A concise and general strategy for the total synthesis of the phenanthroquinolizidine alkaloids has been developed. An iterative Suzuki–Miyaura coupling reaction between the requisite aryl boronic acid, 2-bromo-4,5-dimethoxyphenyl N -methyliminodiacetate (MIDA) boronate derived from boronic acid, and a suitable bromopyridine substrate bearing a homopropargyl alcohol at the 2-position generated the desired ortho -aza-terphenyl compounds. Hydrogenation of the triple bond followed by treatment with methanesulfonyl chloride afforded their corresponding tetrahydroquinolizinium ion intermediates, which were subsequently reacted with NaBH 4 to provide the desired hexahydroquinolizine products. A final oxidative electrocyclization reaction gave the target phenanthroquinolizidine natural products. This synthetic approach only requires the use of three chromatographic separations throughout the entire synthesis.",10.1021/acs.joc.9b01768,2019-08-26,0.584198313518539
Tetrahedron,"A new asymmetric 1,4-addition method: application to the synthesis of the HIV non-nucleoside reverse transcriptase inhibitor DPC 961",,10.1016/s0040-4039(00)00331-2,2000-04-01,0.5841918097092109
Organic Process Research & Development,Investigation of an Alternative Route to ZD3638 and Cost-Benefit Analysis Comparison of Raw Materials with the Previous Route,A convergent synthesis to ZD3638 was proposed starting with alternative raw materials. A cost-benefit analysis for the new route was performed which demonstrated that significant savings in raw materials costs could be made over the previous linear sequence. The convergent route was then proved in principle by experimental work. LiTMP was shown to be a superior base to LDA in the modified lithiation reaction.,10.1021/op0000935,2001-07-17,0.5841891395077897
Tetrahedron,A short and efficient synthesis of 4-hydroxy-5-(1-hydroxyalkyl)-γ-butyrolactones,,10.1016/s0040-4039(01)90024-3,1984-01-01,0.5841841447381957
Organic Process Research & Development,"Nucleophilic Aromatic Substitutions of 2-Halo-5-(sulfamoyl)benzoic Acids and <i>N</i>,<i>O</i>-Bis-alkylation via Phase Transfer Catalysis: Synthesis of RoRγ Inverse Agonist GSK2981278A","GSK2981278A ( 1 ) is a RORγ inverse agonist used as a potential topical nonsteroidal therapy for psoriasis. New synthesis of 1 was developed based on a S N Ar reaction of (tetrahydro-2 H -pyran-4-yl)methanol with an aryl halide intermediate, prepared from 2-halobenzoic acids. The dianion underwent in situ N, O -bis-isobutylation, followed by a reduction to provide 1 . The new route eliminated a genotoxic tosylate of (tetrahydro-2 H -pyran-4-yl)methanol and a difficult reductive amination from the original synthesis starting from methyl salicylate. A primary version of the route has been scaled up to deliver 125 kg of 1 . However, the heating of a strong base in DMSO for an extended period during the bis-alkylation was found to be a safety concern for manufacturing. A safer and greener process was then developed utilizing a facile N, O -bis-alkylation, which was conducted under phase transfer conditions with mild bases such as potassium carbonate and in green solvents such as water. The concise four stage sequence from 2-halobenzoic acids to GSK2981278A ( 1 ) had an overall yield of 41%.",10.1021/acs.oprd.9b00147,2019-06-03,0.5841839803917186
Organic Letters,Sharpless Asymmetric Dihydroxylation of 5-Aryl-2-vinylfurans:  Application to the Synthesis of the Spiroketal Moiety of Papulacandin D,"[formula: see text] Using the Sharpless catalytic asymmetric dihydroxylation reaction on 5-aryl-2-vinylfurans, diols are produced in high enantioexcess. The resulting diols can be efficiently transformed into the spiroketal ring precursor of the antifungal compound papulacandin D. Stereoselective reduction of this precursor followed by a diastereoselective dihydroxylation completes the synthesis of a mannopyranoside isomer of a papulacandin derivative.",10.1021/ol0000253,2000-03-01,0.5841827323408727
Synlett,Synthesis and Biological Evaluation of Furano-Epothilone C,An efficient synthesis of furano-epothilone C (1) is described by the use of an aldol reaction and a ring-closing metathesis (RCM) for the closure of the macrocyclic ring system. This new type of analog contains a furan ring in the C8-C10 region of the macrocycle. The biology of this new class of epothilone C analog has been studied.,10.1055/s-2004-829071,2004-01-01,0.5841819147249305
European Journal of Organic Chemistry,Syntheses of a Flobufen Metabolite and Dapoxetine Based on Enantioselective Allylation of Aromatic Aldehydes,"Abstract The enantioselective allylation of an aromatic aldehyde to give a chiral homoallylic alcohol was employed as the key step in the syntheses of a flobufen metabolite and dapoxetine. In the former case, the homoallylic alcohol moiety (99 % ee ) was converted into a five‐membered lactone ring with good preservation of the optical purity, and the target compound, a flobufen metabolite, was obtained in 95 % ee . In the latter case, the homoallylic alcohol moiety (97 % ee ) was transformed over several steps into a 3‐aminopropanol moiety. During the course of the synthesis, the gradual loss of optical purity was observed, and the target compound, dapoxetine, was obtained in 85 % ee .",10.1002/ejoc.201301899,2014-02-24,0.5841798701028246
Organic Letters,"Furanosteroid Studies. Stereoselective Synthesis of the A,B,E-Ring Core of Wortmannin","Alkyne oxazole 11c is converted in three steps, and approximately 45% overall yield, to furanolactone 21alpha having the A,B,E-ring core of the wortmannin (2) family of furanosteroids. The TiCl4-catalyzed insertion of EtO2C-CH=O between C3 and C10 in furanoacid 14d is >98% stereoselective via a pathway involving chemoselective lactonization of equilibrating aldol intermediates 23alpha,beta (dynamic kinetic resolution).",10.1021/ol071158s,2007-07-26,0.5841796409489642
European Journal of Organic Chemistry,"Efficient Synthesis of 1,4,7‐Triazacyclononane and 1,4,7‐Triazacyclononane‐Based Bifunctional Chelators for Bioconjugation","Abstract The reaction of diethylenetriamine with chloroacetaldehyde yielded a bicyclic aminal intermediate for the synthesis of 1,4,7‐triazacyclononane (TACN), a macrocyclic polyamine the derivatives of which find applications as catalysts, bleaching agents, and chelators for medical imaging. This new synthetic protocol outperforms the synthetic methods described so far because it does not involve any cyclization step. Moreover, this aminal intermediate allowed access to a new family of TACN derivatives functionalized on the carbon skeleton, for example, C ‐aminomethyl‐TACN. This novel compound is a precursor of valuable bifunctional chelating agents for nuclear medicine, in particular, for the preparation of PET imaging agents after bioconjugation and metallation with 68 Ga or 64 Cu.",10.1002/ejoc.201402708,2014-09-04,0.5841704335387884
Synlett,Bioinspired Total Synthesis of Marine Anticancer Meroterpenoids Dysideanone B and Dysiherbol A and Structure Revision of Dysiherbol A,"Abstract Our recent progress on the total synthesis of marine anticancer sesquiterpene quinone/hydroquinone dysideanone B and dysiherbol A is briefly highlighted. This success relied on some key transformations. The union of the terpene and quinone/hydroquinone moieties was realized through a site and stereoselective α-position alkylation of Wieland–Miescher ketone derivative with a bulky benzyl bromide. The 6/6/6/6-tetracycle of dysideanone B was constructed using an intramolecular radical cyclization and the 6/6/5/6-fused core structure of dysiherbol A was forged by an intramolecular Heck reaction, respectively. The possible origin of ethoxy group in dysideanone B was revealed by mimicking the isolation conditions at a late stage. The structure of dysiherbol A was revised through the total synthesis of this natural product. Schmalz’s synthesis of dysiherbol A was also included.",10.1055/a-1546-2572,2021-07-08,0.5841672267380758
Organic Letters,Sc(OTf)<sub>3</sub>-Catalyzed Dehydrogenative Cyclization for Synthesis of <i>N</i>-Methylacridones,"A novel method has been developed for the synthesis of substituted N-methylacridones from 2-(N-methyl-N-phenylamino)benzaldehydes via dehydrogenative cyclization. This transformation involves two primary processes: the aldehyde first coordinates with Sc(OTf)3 and induces the aromatic electrophilic substitution (S(E)Ar) reaction to form the active intermediate N-methyl-acridin-9-ol, which is then quickly oxidized in situ to afford the acridones. Furthermore, the procedure involved is both environmental friendly and atom efficient; H2O is the only byproduct in this reaction.",10.1021/ol400371h,2013-03-29,0.5841646291213646
Journal of Organic Chemistry,"A New Concise Strategy for Synthesis of Dibenzo[<i>b,f</i>]thiepins and Related Fused Symmetrical Thiepin Derivatives","A new strategy for preparation of dibenzo[b,f]thiepins and related fused systems in good overall yields is described, featuring ortho-metalation of aromatic or heterocyclic aldehyde acetals followed by treatment with bis(phenylsulfonyl) sulfide for construction of the required bis(aryl)- or bis(heteroaryl) sulfide precursors, which were thereafter subjected to deacetalization, and finally McMurry coupling as the ring-forming step.",10.1021/jo701627g,2007-10-12,0.5841637471900892
Tetrahedron,Synthesis of 5-substituted 4--methyl tetramates,,10.1016/s0040-4039(00)85192-8,1986-01-01,0.584163518738474
Organic Letters,Stereoselective Synthesis of Dienyl-Carboxylate Building Blocks: Formal Synthesis of Inthomycin C,"A direct synthesis of stereodefined halodienes is reported. Those key building blocks enable a concise access to polyenic products, as demonstrated in a modular synthesis of Inthomycin C.",10.1021/ol401226y,2013-06-13,0.5841602041068341
Organic Letters,Application of Two Direct C(sp<sup>3</sup>)–H Functionalizations for Total Synthesis of (+)-Lactacystin,"Herein, we report a new synthetic route from (S)-pyroglutaminol to (+)-lactacystin, a potent inhibitor of the 20S proteasome. The photoinduced intermolecular C(sp(3))-H alkynylation and intramolecular C(sp(3))-H acylation chemo- and stereoselectively constructed the tetra- and trisubstituted carbon centers, respectively. The obtained bicycle was transformed into the target compound in a concise manner. The present total synthesis demonstrates the power of the direct C(sp(3))-H functionalizations for the assembly of multiple functionalized structures of natural products.",10.1021/ol503291s,2014-12-19,0.5841582925012522
Tetrahedron,An improved method for the regioselective synthesis of highly substituted quinolines from Morita–Baylis–Hillman adducts,,10.1016/j.tetlet.2015.03.090,2015-04-06,0.5841471873365595
Tetrahedron,"Chaetominedione, a new tyrosine kinase inhibitor isolated from the algicolous marine fungus Chaetomium sp.",,10.1016/j.tetlet.2008.08.064,2008-08-24,0.5841463856094692
Organic Letters,Short Scalable Route to <i>Apiaceae</i> Sesquiterpene Scaffolds: Total Synthesis of 4-<i>epi</i>-Epiguaidiol A,"The oxy-Cope/ene reaction cascade to form a locked elemane conformer allows the short scalable synthesis of versatile Apiaceae scaffolds. The divergent fate of the obtained macrocyclic germacrane is surveyed under cationic and dioxygen-induced Prins-type reaction conditions to allow the diastereoselective synthesis of oxidized Apiaceae guaiane congeners and the total synthesis of 4- epi -epiguaidiol A. Additionally, the unprecedented reduction of a hydrogen-bond-biased guaiane substrate permits the chemoselective synthesis of desoxo-jungiaguaiane.",10.1021/acs.orglett.2c03215,2022-10-20,0.5841437591008504
Organic Letters,Direct Synthesis of Chiral NH Lactams via Ru-Catalyzed Asymmetric Reductive Amination/Cyclization Cascade of Keto Acids/Esters,"Lactams with a stereogenic center adjacent to the N atom have existed in many medicinal agents and bioactive alkaloids. Herein we report a broadly applicable synthesis of enantioenriched NH lactams through a one-pot asymmetric reductive amination/cyclization sequence of easily available keto acids/esters. Such cascade processes alleviate the demand for protecting group manipulations as well as intermediate purification. This strategy is capable of constructing enantioenriched lactams and benzo-lactams of a five-, six-, or seven-membered ring in generally high yield and with excellent enantioselectivities (up to 97% ee). Scalable and concise syntheses of key drug intermediates have further displayed the importance of this methodology.",10.1021/acs.orglett.0c00669,2020-03-19,0.5841403714901182
Journal of Organic Chemistry,Synthesis of a New<i>trans</i>-A<sub>2</sub>B<sub>2</sub>Phthalocyanine Motif as a Building Block for Rodlike Phthalocyanine Polymers,"Polyphthalocyanines have potential application in the development of electronic materials. One-dimensional polyphthalocyanines are accessible through monomers having a trans-A2B2 structure, but the preparation of a truly linear polyphthalocyanine is challenging because of limitations imposed by the geometry of phthalocyanines and the methodology for their synthesis. Benzimidazoporphyrazines are a known class of extra-annulated phthalocyanines. A trans-A2B2 benzimidazoporphyrazine is geometrically suitable for the preparation of rodlike polymers. A new synthesis of benzimidazoporphyrazines is presented as a stepping stone to the synthesis of trans-A2B2 benzimidazoporphyrazines.",10.1021/jo052122l,2006-03-30,0.5841347718658619
Journal of Organic Chemistry,Synthesis of (+)-Didemniserinolipid B: Application of a 2-Allyl-4-fluorophenyl Auxiliary for Relay Ring-Closing Metathesis,"The synthesis of didemniserinolipid B utilizing a ketalization/ring-closing metathesis (K/RCM) strategy is described. In the course of this work, a novel 2-allyl-4-fluorophenyl auxiliary for relay ring-closing metathesis (RRCM) was developed, which increased the yield of the RCM. The resulting 6,8-dioxabicyclo[3.2.1]octene core was selectively functionalized by complimentary dihydroxylation and epoxidation routes to install the C10 axial alcohol. This bicyclic ketal core was further functionalized by etherification and an alkene cross metathesis with an unsaturated alpha-phenylselenyl ester en route to completing the total synthesis.",10.1021/jo801666t,2008-09-24,0.5841340278461206
Synthesis,"First Stereoselective Total Synthesis of Cryptomoscatone D2 and Syntheses of (5R,7S)-Kurzilactone and (+)-Cryptofolione by an Asymmetric Acetate Aldol Approach","An efficient concise stereoselective total synthesis of cryptomoscatone D2 and syntheses of (5 R ,7 S )-kurzilactone and (+)-cryptofolione, based on an asymmetric acetate aldol reaction starting from trans -cinnamaldehyde, are described. The other key reactions are a Horner–Wadsworth–Emmons reaction, a Brown’s asymmetric allylation and a ring-closing metathesis.",10.1055/s-0031-1290771,2012-04-05,0.5841291709097397
Organic Letters,Construction of BCDEF Core of Andilesin C,"A synthetic study toward the BCDEF core skeleton of andilesin C is presented. Key elements involved iron-promoted intramolecular perezone-type [5 + 2] cycloaddition to install the BCD ring system simultaneously in a one-step, copper-catalyzed intramolecular cyclopropanation followed by BiCl 3 -promoted retro-aldol reaction to construct ring E and a one-pot manipulation involving reduction, lactonization, and isomerization to introduce the lactone ring F. We finally synthesized the congested BCDEF ring system of andilesin C, featuring four quaternary centers and two tertiary centers, by following a strategy with a 15-pot reaction and 11 purification operations.",10.1021/acs.orglett.9b02791,2019-09-13,0.5841223552120023
Tetrahedron,"Convenient, scalable synthesis of 2-methyl-3-(3′,3′-carboxymethylpropyl)-1,4-naphthoquinone, the principal vitamin K urinary metabolite",,10.1016/j.tetlet.2016.11.043,2016-11-09,0.5841132881469939
Journal of Organic Chemistry,SmI<sub>2</sub>-Mediated Cyclizations of Derivatized β-Lactams for the Highly Diastereoselective Construction of Functionalized Prolines,"A series of C4-keto-functionalized 1-[(benzoyloxy)(ethoxycarbonyl)methyl]-2-azetidinones were prepared and studied for their tendency to undergo a Reformatsky-type cyclization to fused bicyclic or tricyclic beta-lactams with the single-electron reducing agent samarium diiodide. Whereas the azetidinone 21a underwent reductive cyclization, affording the potent antibiotic sanfetrinem's tricyclic [4.5.6] core structure as the major component, all other examples tested resulted in cyclization followed by an N to O acyl migration involving cleavage of the beta-lactam ring as the favored pathway. Highly functionalized proline derivatives were therefore accessed as single diastereomers through the reductive cyclization of benzoates 21b, 22, 23a,b, 24b, and 25-28. Pertinent for the success of these cyclizations was the addition of 1 equiv of tert-butyl alcohol, allowing for the protonation of the basic amide derivative obtained after the acyl migration step. The diastereoselectivities of these reactions deviate from those of similar cyclizations involving the corresponding lithium enolate. This divergence could be rationalized by the coordination of the metal ion of the samarium(III) enolate intermediate to the beta-lactam amide functionality in the cyclization step, which may not be possible for lithium enolates.",10.1021/jo0104983,2002-03-19,0.584101668510447
Tetrahedron,A new iodine catalyzed regioselective synthesis of xanthene synthons,,10.1016/j.tetlet.2012.04.061,2012-04-21,0.5841001746669262
Journal of Organic Chemistry,Pd-Catalyzed Decarboxylative Cycloaddition of Vinylethylene Carbonates with Isothiocyanates,"An efficient route for formal [3 + 2] cycloaddition of vinylethylene carbonates with isothiocyanates was developed for the synthesis of 1,3-oxazolidine-2-thione derivatives. The zwitterionic π-allyl palladium intermediates formed in situ by decarboxylation of VECs acted as the three-membered synthons. In this transformation, the C-N bond formation was selectively realized over the C-S bond formation.",10.1021/acs.joc.0c00243,2020-06-17,0.584094210555328
Organic Letters,"Total Synthesis of (+)-Coriamyrtin via a Desymmetrizing Strategy Involving a 1,3-Cyclopentanedione Moiety","We describe the total synthesis of (+)-coriamyrtin, which bears a highly functionalized cis -hydrindane skeleton and is a widely known neurotoxin of the Coriariaceae family. Our synthetic strategy involves the highly stereoselective construction of the cis -hydrindane skeleton via a desymmetrizing strategy involving a 1,3-cyclopentanedione moiety using an intramolecular aldol reaction and the formation of the 1,3-diepoxide moiety of coriamyrtin through the elaborate functionalization of the cyclopentane ring in the bicyclic structure.",10.1021/acs.orglett.3c00249,2023-02-28,0.5840893039280485
Journal of the American Chemical Society,From Styrenes to Enantiopure α-Arylglycines in Two Steps,"Direct enantioselective synthesis of ( R )- and ( S )- N- Cbz- or N- BOC-protected α-arylglycinols from styrenes via catalytic asymmetric aminohydroxylation, with enantioselectivities up to 99% and isolated yields up to 80%, is described. In a subsequent oxidation step, these glycinols yield the corresponding carbamate-protected α-arylglycines.",10.1021/ja9728177,1998-01-30,0.5840890359026629
Organic Letters,Total Synthesis of (±)-Mersicarpine,"The first total synthesis of the indole alkaloid mersicarpine is reported. Key steps include a beta-dicarbonyl radical cyclization, as well as an oxidation of the benzopyrrole moiety to establish the masked 1,2-dicarbonyl functionality. An X-ray crystal structure and discussion of the 1H NMR behavior of the natural product are also presented.",10.1021/ol800259s,2008-03-12,0.5840813002754701
Organic Letters,A General Method for Synthesis of Unclosed Cryptands via H-Bond Templated Macrocyclization and Subsequent Mild Postfunctionalization,"A practical four-step synthesis of a model 26-membered N-Boc-protected macrocycle, starting from commercially available and inexpensive materials, is reported. The crucial macrocyclization step does not require high-dilution conditions and is completed in a short time (8 h). The high yield of macrocyclization (61%) is achieved owing to templation by intramolecular H-bonds and a chloride anion, which both help to adopt a favorable folded conformation of the open-chain intermediate. Finally, mild, selective, and efficient incorporation of intraannular amide function leading to five diversely functionalized unclosed cryptands (UCs) is described.",10.1021/acs.orglett.5b02324,2015-09-11,0.5840748412395362
Journal of Organic Chemistry,Rhodium-Catalyzed Cyclohydrocarbonylation Approach to the Syntheses of Enantiopure Homokainoids,"Homologues of kainic acid, a naturally occurring potent glutamate receptor agonist, were designed based on a rigidified pipecolinoglutamic acid structure and can be regarded as homokainoids for their potential activities in the central nervous system. These novel homokainoids in an enantiomerically pure form were synthesized from enantiopure (R)- and (S)-Garner's aldehyde, featuring (i) the highly diastereoselective addition of alkenylcuprates to the acrylate intermediates and (ii) the Rh-catalyzed cyclohydrocarbonylation of homoallylic amine intermediates to construct the functionalized piperidine moiety in the key steps. For the introduction of a substituent at the 4- or 5-position of pipecolinoglutamic acid, a few different strategies were used, which successfully led to the formation of enantiopure homokainoids.",10.1021/jo070942n,2007-11-14,0.5840736606543351
Synthesis,A Synthesis of the Hypocholesterolemic Agent 1233A Via Asymmetric [2 + 2] Cycloaddition,All articles of this category diene synthesis - coupling - [2 + 2] cycloaddition - β -lactone - chiral Lewis acid - carboxylation - Pfaltz reduction,10.1055/s-1998-2194,1998-11-01,0.5840708516656167
Organic Process Research & Development,"The Discovery and Development of a Safe, Practical Synthesis of ABT-869","The discovery, development and implementation of two chemical routes to ABT-869 is reported. Optimization of the first-generation heterocycle formation and Suzuki coupling is briefly described. Key features of the second-generation synthesis include the development of a safe hydrazine condensation by utilizing an inorganic base to increase the onset temperature of exothermic decomposition. The second-generation Suzuki reaction is discussed in detail, culminating in the use of an oxygen monitor as a PAT to maximize reproducibility on scale.",10.1021/op900208y,2009-10-28,0.5840705589707841
Journal of Organic Chemistry,Development of a Commercial Process To Prepare AMG 232 Using a Green Ozonolysis–Pinnick Tandem Transformation,"A robust process to manufacture AMG 232 was developed to deliver drug substance of high purity. Highlights of the commercial process development efforts include the following: (i) use of a novel bench-stable Vilsmeier reagent, methoxymethylene- N, N-dimethyliminium methyl sulfate, for selective in situ activation of a primary alcohol intermediate; (ii) use of a new crystalline and stable isopropyl calcium sulfinate reagent ensuring robust preparation of a sulfone intermediate; (iii) development of a safe ozonolysis process conducted in an aqueous solvent mixture in either batch or continuous manufacturing mode; and (iv) control of the drug substance purity by crystallization of a salt rejecting impurities effectively. The new process was demonstrated to afford the drug substance (99.9 LC area %) in 49.8% overall yield from starting material DLAC (1).",10.1021/acs.joc.8b02390,2018-12-17,0.5840681718787416
Tetrahedron,A facile and efficient synthesis of 4β-aminopodophyllotoxins,,10.1016/s0040-4039(99)00125-2,1999-03-01,0.5840664466968158
Tetrahedron,A convergent synthetic strategy for the polyene macrolide pimaricin,,10.1016/s0040-4039(00)88094-6,1983-01-01,0.5840613671420968
Journal of the American Chemical Society,Enantioselective Total Synthesis of (−)-Rubriflordilactone B by a Bioinspired Skeletal Reorganization Approach,"bisnortriterpenoid with a unique 5/5/7/6/5/5-hexacyclic framework that includes a characteristic tetrasubstituted aromatic ring. Herein, we report a convergent, enantioselective total synthesis of this natural product by a bioinspired skeletal reorganization approach. Key transformations include a chelation-controlled [2,3]-Wittig-Still rearrangement to assemble the western cyclohexenyl fragment with complete diastereocontrol, a Cu(II)-catalyzed tandem acyloin acylation-Wittig olefin to build the eastern butanolide fragment, a Friedel-Crafts cyclization to construct the seven-membered ring, and an E1cB reaction/transesterification/oxa-Michael addition cascade to forge the pivotal 5/5-fused bicyclic lactone. This work vividly demonstrates that bioinspired skeletal reorganization is a useful strategy for simplifying the retrosynthetic analysis of structurally complex natural products.",10.1021/jacs.4c18292,2025-02-17,0.5840497888845212
Journal of Organic Chemistry,Construction of a <i>cis</i>-Cyclopropane via Reductive Radical Decarboxylation. Enantioselective Synthesis of <i>cis-</i> and <i>trans-</i>1-Arylpiperazyl-2-phenylcyclopropanes Designed as Antidopaminergic Agents,"(1S,2S)-, (1S,2R)-, and (1R,2S)-1-(2,4-Dimethylphenyl)piperazyl-2-phenylcyclopropane (2a, 3, and ent-3, respectively), which were designed as conformationally restricted analogues of haloperidol (1), a clinically effective antipsychotic agent, were synthesized from chiral epichlorohydrins using the Barton reductive radical decarboxylation as the key step. (1S,2R)-1-(tert-Butyldiphenylsilyloxy)methyl-2-carboxy-2-phenylcyclopropane (5), which was prepared from (S)-epichlorohydrin ((S)-7), was converted into its N-hydroxypyridine-2-thione ester 12, the substrate for the reductive radical decarboxylation. When 12 was treated with TMS3SiH in the presence of Et3B or AIBN, the decarboxylation and subsequent hydride attack on the cyclopropyl radical intermediate from the side opposite to the bulky silyloxymethyl moiety occurred, resulting in selective formation of the corresponding reductive decarboxylation product 4-cis with the cis-cyclopropane structure. From 4-cis, the cis-cyclopropane-type target compound 3 was readily synthesized. Starting from (R)-epichlorohydrin ((R)-7), ent-3 was similarly synthesized. Epimerization of the cyclopropanecarboxamide ent-16-cis, a synthetic intermediate for ent-3, on treatment with a base prepared from Bu2Mg and i-Pr2NH in THF occurred effectively to give the corresponding trans isomer 16-trans, which was converted into 2a with the trans-cyclopropane structure.",10.1021/jo0302206,2003-11-01,0.5840491452583878
Tetrahedron,"The synthesis of 1,2,3-trichloro- and 2,3-dichlorobicyclo[2.2.1]hept-2-en-7-one. A selective reduction of bridgehead chlorine.",,10.1016/s0040-4039(01)97753-6,1969-01-01,0.5840486100952826
Synthesis,Asymmetric Synthesis of Tetrahydro-β-carboline Alkaloids Employing Ellman’s Chiral Auxiliary,"A stereoselective synthesis of tetrahydro-β-carboline alkaloids has been accomplished using Ellman’s sulfinamide as a chiral source. This is the first report on the synthesis of chiral tetrahydro-β-carboline natural products using tert -butanesulfinamide through haloamide cyclization. Similarly, the synthesis of an indolizino[8,7- b ]indole alkaloid, (–)-harmicine, has been achieved by means of allylation of an N -sulfinylimine, hydroboration, and S N 2 substitution.",10.1055/s-0035-1561562,2016-02-05,0.5840463706581943
Tetrahedron,A concise route for the preparation of nucleobase-simplified cADPR mimics by click chemistry,,10.1016/j.tetlet.2008.05.076,2008-05-22,0.584045374462714
Journal of Organic Chemistry,Synthesis of Carbolines by Photostimulated Cyclization of Anilinohalopyridines,"A general synthetic route to prepare all four carboline regioisomers by photostimulated cyclization of anilinohalopyridines is described. The methodology affords various substituted carbolines in good to excellent yields. In the case of α-carbolines, the S(RN)1 methodology complements previously reported palladium-catalyzed cyclization approaches.",10.1021/jo200923n,2011-07-08,0.5840367483550417
Synthesis,"A Practical Synthesis of 2-{4-[4-Fluoro-3-(trifluoromethyl)phenyl]-2-(piperidin-4-yl)-1H-imidazol-1-yl}-N,N-dimethylethanamine","A practical synthesis of the title compound was accomplished by hydrogenation of 2-{4-[4-fluoro-3-(trifluoromethyl)phenyl]-2-(pyridin-4-yl)-1 H -imidazol-1-yl}- N , N -dimethylethanamine. The latter was obtained by N-alkylation of 4-{4-[4-fluoro-3-(trifluoromethyl)phenyl]-1 H -imidazol-2-yl}pyridine. Treatment of N -{2-[4-fluoro-3-(trifluoromethyl)phenyl]-2-oxoethyl}isonicotinamide hydrochloride with ammonium acetate in acetic acid provided 4-{4-[4-fluoro-3-(trifluoromethyl)phenyl]-1 H -imidazol-2-yl}pyridine. Coupling of 2-amino-1-[4-fluoro-3-(trifluoromethyl)phenyl]ethanone 4-methylbenzene sulfonate with pyridine 4-carboxylic acid using either T 3 P or EDCI-HOBt provided N -{2-[4-fluoro-3-(trifluo­romethyl)phenyl]-2-oxoethyl}isonicotinamide hydrochloride.",10.1055/s-0031-1290371,2012-06-13,0.5840350080676748
Tetrahedron,Synthetic studies toward potent cytostatic macrolide rhizopodin: stereoselective synthesis of the C16–C28 fragment,,10.1016/j.tetlet.2010.10.142,2010-11-01,0.5840341978721735
Synlett,Synthesis of Amphiphilic Piperidinium Derivatives. Cationic Lipids 41,"All articles of this category A series of novel amphiphilic piperidinium salts for use in cationic liposome mediated gene transfection was prepared. The synthesis involves the introduction of the lipophilic part of the cationic lipid through formation of biodegradable ester bonds, with subsequent alkylation of the heterocyclic nitrogen atoms to complete the lipid polar head group. cationic lipids - cationic liposomes - gene transfection - drug delivery - piperidinium derivatives",10.1055/s-1996-5576,1996-07-01,0.5840282684482215
Tetrahedron,Synthesis of chiral butenolides using amino-thiocarbamate-catalyzed asymmetric bromolactonization,,10.1016/j.tetlet.2014.01.009,2014-01-08,0.5840273635449212
Tetrahedron,Enantioselective synthesis of the ester side chain of homoharringtonine,,10.1016/s0040-4039(01)00086-7,2001-03-01,0.5840253039862147
Tetrahedron,"Efficient synthesis of highly substituted benzoselenazole derivatives through the one-pot, multi-step Ullmann coupling reaction",,10.1016/j.tetlet.2024.155387,2024-11-23,0.5840223919664437
Journal of Organic Chemistry,Bioinspired Synthesis of the Furopyrazine Alkaloid Hyrtioseragamine A,"A biosynthetic hypothesis proposed herein was used to guide the total synthesis of the marine-derived alkaloid hyrtioseragamine A. In the key biomimetic step, an enedione underwent acid-mediated isomerization-cyclodehydration to form the rare furopyrazine core of the natural product. The spectroscopic data for the synthetic sample is in full agreement with that described in the isolation report.",10.1021/acs.joc.1c00174,2021-03-09,0.5840148300434607
Journal of Organic Chemistry,Synthetic Study of Dragmacidin E: Enantioselective Construction of the Seven-Membered Ring-Fused Indole Skeleton with Contiguous Stereocenters,"We developed an enantioselective synthetic method of constructing a seven-membered ring-fused indole skeleton with contiguous stereocenters for the synthesis of dragmacidin E. Introduction of chirality at the benzylic position was achieved by Ir-catalyzed asymmetric hydrogenation. After construction of the tricyclic molecular framework using Pd-catalyzed cascade cyclization, the tetrasubstituted carbon center was created using the Ag nitrene-mediated C-H amination reaction. The developed method provided access to the functionalized seven-membered ring-fused indole skeleton with a hydroxymethyl branch in the tetrasubstituted carbon.",10.1021/acs.joc.2c02216,2023-01-26,0.5840022637684952
Tetrahedron,New facile synthesis of substituted 2-benzylidene-pyrrolidines by the anionic cyclization of δ-alkynylamines,,10.1016/s0040-4039(00)98070-5,1990-01-01,0.5840022500104554
Synlett,New Synthetic Route to the Highly Strained Cores of C-1027 and Neocarzinostatin Chromophores,All articles of this category Efficient construction of the bicyclo[7.3.0]dodecenediyne cores of chromophore of C-1027 ( 1 ) and neocarzinostatin ( 2 ) was obtained via the C-C bond formation at C5-C6 using the LiN(SiMe 3 ) 2 /CeCl 3 -mediated acetylide-aldehyde condensation reaction. C-1027 - neocarzinostatin - lithium hexamethyldisilazide - cerium trichloride - acetylide-aldehyde condensation,10.1055/s-1998-1983,1998-12-01,0.5840013852239332
Journal of Organic Chemistry,Concise Syntheses of (−)- and (+)-Syringolide 1 and (−)-Δ<sup>7</sup>-Syringolide 1,"(−)- and (+)-Syringolide 1 have been synthesized from 2,3- O -isopropylidene-β- threo -pentulofuranose ( 1 ), which was readily prepared from d - or l -xylose, respectively. Condensation of 1 with 3-oxooctanoic acid and treatment of the ester with TFA:H 2 O (9:1) produced syringolide 1 in 6.3% yield for the two steps. According to the same synthetic route by replacing 3-oxooctanoic acid with 3-oxo-7-octenoic acid, (−)-Δ 7 -syringolide 1 was prepared in 5.8% yield. Primary β-keto esters of arabinulose and fructose were also prepared to test the selectivity of the biomimetic cyclization to form syringolide analogs.",10.1021/jo970461b,1997-07-01,0.5840006902581362
Journal of the American Chemical Society,Total Syntheses of (+)- and (−)-Peribysin E,"A convergent, stereocontrolled route to either antipode of the cell adhesion inhibitor, peribysin E, has been achieved from carvone. Highlights of the synthesis include a Diels-Alder reaction to generate a cis-decalin framework, followed by semipinacol-type ring contraction to secure the stereochemistry of the C7 quaternary center. Potential mechanistic pathways for the critical ring contraction were studied through deuterium incorporation studies. In addition, an optimized olefin isomerization/Saegusa oxidation protocol is described for the conversion of [4+2] cycloadducts of 2-(trialkylsilyloxy)-1,3-dienes to 1,6(2H,7H)-naphthalenediones, having stereochemical arrangements not accessible via conventional Robinson annulation protocols. Finally, the ability to independently prepare either enantiomer of peribysin E from the corresponding antipode of carvone led to a reassignment of the absolute configuration of peribysin E.",10.1021/ja8048207,2008-09-11,0.5839993855534803
Journal of Organic Chemistry,A Flexible Route to Chiral 2-<i>endo</i>-Substituted 9-Oxabispidines and Their Application in the Enantioselective Oxidation of Secondary Alcohols,"A new and flexible route to enantiomerically pure bi- and tricyclic 9-oxabispidines has been developed with use of (1R,5S)-7-methyl-2-oxo-9-oxa-3,7-diazabicyclo[3.3.1]nonane-3-carboxylic acid tert-butyl ester as the common late-stage intermediate. The 9-oxabispidines synthesized were evaluated as the chiral ligands in the Pd(II)-catalyzed oxidative kinetic resolution of secondary alcohols giving good to excellent selectivity factors of up to 19.",10.1021/jo802409x,2008-12-16,0.5839977061064303
Tetrahedron,A one step synthesis of a pentamethylene-bridged superphane of a CpCo-stabilized cyclobutadiene complex,,10.1016/s0040-4039(00)91718-0,1992-03-01,0.583993535662823
Angewandte Chemie International Edition,Revision of the Absolute Configuration of Salicylihalamide A through Asymmetric Total Synthesis,"A highly E-selective ring-closing metathesis is the key to building the macrocyclic salicylate core of (+)-salicylihalamide A (1). The synthesis results in a reassignment of the absolute configuration of natural (−)-salicylihalamide A (2), a structurally unprecedented antitumor metabolite with a potentially novel mode of action.",10.1002/1521-3773(20001201)39:23<4308::aid-anie4308>3.0.co;2-4,2000-12-01,0.5839730688707201
Tetrahedron,Perchloric acid induced epimerisation of the thevinones: an improved synthesis of 7β-dihydrothevinones,,10.1016/s0040-4039(00)01300-9,2000-09-01,0.5839707415270711
Organic Letters,Wharton-Fragmentation-Based Approach to the Carbocyclic Core of the Phomoidrides,"The carbocyclic core of the phomoidrides has been synthesized efficiently and in high yield. Key steps include a phenolic oxidation/intramolecular Diels-Alder sequence, tandem radical cyclization, and a late-stage Wharton fragmentation of a densely functionalized isotwistane skeleton.",10.1021/ol302011b,2012-08-23,0.5839690443498373
Journal of Organic Chemistry,"First Total Synthesis of (±)-Linderol A, a Tricyclic Hexahydrodibenzofuran Constituent of <i>Lindera umbellata</i> Bark, with Potent Inhibitory Activity on Melanin Biosynthesis of Cultured B-16 Melanoma Cells","The first total synthesis of (+/-)-Linderol A, a hexahydrodibenzofuran constituent of Lindera umbellata bark, with potent inhibitory activity on the melanin biosynthesis of cultured B-16 melanoma cells, was achieved through 19 steps of reaction in 6.6% overall yield, in which the critical step was a tandem reaction of a 3-ethoxycarbonylcoumarin derivative with dimethylsulfoxonium methylide to yield the 2-ethoxycarbonylcyclopenta[b]benzofuran-3-ol derivative.",10.1021/jo020619e,2003-01-07,0.5839648908337075
Tetrahedron,Development of silicon-tethered anionic reaction and its application to the synthesis of chiral A-ring moieties of Taxol™,,10.1016/j.tetlet.2004.09.143,2004-10-12,0.583961825286007
Tetrahedron,Corrigendum to “Development of silicon-tethered anionic reaction and its application to the synthesis of chiral A-ring moieties of Taxol™”,,10.1016/j.tetlet.2004.10.157,2004-12-15,0.583961825286007
Organic Letters,"A Facile Synthesis of Dragmacidin B and 2,5-Bis(6‘-bromo-3‘-indolyl)piperazine","A short synthesis of dragmacidin B (1), 2,5-bis(6'-bromo-3'-indolyl)piperazine (2), and corresponding didebromo analogues 8 and 9 is described. The key steps involve the dimerization of oxotryptamines 4 and 11 to give bis(indolyl)pyrazines 5 and 12, which upon selective reduction and reductive methylation with sodium cyanoborohydride afforded the requisite piperazine natural products.",10.1021/ol0001970,2000-09-14,0.58396115799012
European Journal of Organic Chemistry,"Concise Total Synthesis of Dihydrocorynanthenol, Protoemetinol, Protoemetine, 3‐<i>epi</i>‐Protoemetinol and Emetine","Abstract A concise asymmetric assembly of secologanine tryptamine and dopamine alkaloids by means of a one‐pot three‐component cascade reaction methodology is disclosed. This is demonstrated by the expeditious total syntheses of (–)‐dihydrocorynanthenol, (–)‐protoemetinol, (–)‐protoemetine, (–)‐3‐ epi ‐protoemetinol, and emetine (3–6 steps). The biomimetic synthetic strategy involved the following key steps: (i) One‐pot three‐component highly enantioselective catalytic Michael/Pictet–Spengler/lactamization cascade reactions; (ii) One‐pot tandem Swern oxidation/Wittig sequences; (iii) One‐pot tandem hydrogenation sequences.",10.1002/ejoc.201101296,2011-11-16,0.5839554853759344
Tetrahedron,Total synthesis of NADH:ubiquinone oxidoreductase (complex I) antagonist pterulone and its analogue,,10.1016/s0040-4039(01)01580-5,2001-10-01,0.583954678489859
Synlett,Stereoselective Synthesis of a Bicyclic Isoxazolidine Related to the Pyrinodemin Family of Alkaloids via an Intramolecular Asymmetric [2+3] Cycloaddition,"Bicyclic isoxazolidine 21, a synthetic intermediate for pyrinodemins, was synthesized in six steps using an asymmetric intramolecular [2+3] cycloaddition of a new phenylglycinol-derived oxazoline N-oxide",10.1055/s-2004-836049,2004-11-29,0.5839508131663077
Synlett,Racemic Synthesis of the New Antibiotic Tetramic Acid Reutericyclin,"All articles of this category The synthesis of the new bacteriocidal compound reutericyclin, 3-acetyl-1-(2- trans -decenoyl)-2-hydroxy-5-isobutyl-Δ 2 -pyrrolin-4-one, is performed by coupling of N -(2- trans -decenoyl)-l-leucine to Medlrum's acid followed by cyclization. The resulting N -acylated tetramic acid is directly C-acetylated in position 3. HPLC-purification on RP-C 18 gave racemic reutericyclin in high purity. 2D-NMR and FT-ICR-MS data are identical with those of natural reutericyclin. antibiotics - acylation - Lewis acid catalysis - cyclization",10.1055/s-2000-6734,2000-01-01,0.5839486572334632
Journal of Organic Chemistry,Total Synthesis of (+)-Isatisine A,"The asymmetric total synthesis of (+)-isatisine A has been accomplished commencing with a Lewis acid-catalyzed cyclization of homochiral (S)-vinylcyclopropane diester and N-tosylindole-2-carboxaldehyde to construct the tetrahydrofuran ring. A palladium-catalyzed oxidative decarboxylation was utilized to obtain the dihydrofuran required for the subsequent dihydroxylation reaction to install the diol present on the tetrahydrofuran ring. The total synthesis was completed by an indole oxidation and electrophilic aromatic substitution sequence to construct isatisine A acetonide, which was then carried forward to the antipode of the natural product. The absolute configuration of the natural enantiomer (-)-isatisine A was determined to be C2(S), C9(R), C10(S), C12(R), and C13(R).",10.1021/jo101209y,2010-09-21,0.5839486360106123
Tetrahedron,A novel synthesis of 3-phenyl-4-hydroxy-coumarins,,10.1016/s0040-4039(00)62010-5,1966-01-01,0.5839411932870993
Organic Letters,Spirodiepoxide Strategy to the C Ring of Pectenotoxin 4: Synthesis of the C1−C19 Sector,"The synthesis of a C1-C19 precursor to pectenotoxin 4 is presented. The strategy employed the functionalized allene shown. Key features include: olefin metathesis of two simple fragments to prepare the left portion of the allene-precursor, diastereoselective propargylation of an epoxy aldehyde to form the right portion, use of the DMDO-stable m-fluorobenzyl ether, and an allene spirodiepoxidation/C-ring formation cascade.",10.1021/ol902984e,2010-02-02,0.5839384141356585
Organic Process Research & Development,"Concise Synthesis of Two β-Adrenergic Blocking Agents in High Stereoselectivity Using the Readily Available Chiral Building Block (2<i>S</i>,2′<i>S</i>,2″<i>S</i>)-Tris-(2,3-epoxypropyl)-isocyanurate","A concise synthesis of ( S )-propranolol and ( S )-metoprolol in high stereoselectivity using the readily available chiral building block (2 S,2′ S,2″ S )-tris-(2,3-epoxypropyl)-isocyanurate (S-TGT) as the key intermediate is described.",10.1021/op2001518,2011-08-24,0.5839370306090313
European Journal of Organic Chemistry,An Efficient Ruthenium‐Catalyzed Formal Synthesis of (−)‐Isoavenaciolide,"Abstract A formal synthesis of (−)‐isoavenaciolide ( 1 ) by two different routes is reported. The first approach, leading to a key precursor 2 of (−)‐isoavenaciolide ( 1 ), features the stereoselective construction of the three contiguous stereogenic centers by Evans diastereoselective reduction ( d . e . = 80%) of β‐hydroxy ketone 8 . In the more efficient second approach, the nine‐step sequence leading to the key precursor 2 involves sequential ruthenium‐catalyzed hydrogenation reactions of β‐keto ester 4 and β‐hydroxy ketone 14 to form the two hydroxyl groups with an excellent control of the anti stereochemistry ( d . e . = 99%). (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2004)",10.1002/ejoc.200400047,2004-05-12,0.58393445888576
Tetrahedron,Studies towards the synthesis of diazonamide A. Synthesis of the 4-(oxazol-5-ylmethyl) aryltryptamine fragment,,10.1016/s0040-4039(00)01121-7,2000-08-01,0.5839319383297917
European Journal of Organic Chemistry,Intramolecular Cycloaddition Reactions of ω-Unsaturated Chiral Nitrones,"The intramolecular 1,3-dipolar cycloaddition of ω-un-saturated chiral nitrones is described. Starting materials for this reaction are O-protected chiral cyanohydrins, prepared by an R-oxynitrilase catalyzed asymmetric addition of hydrogen cyanide to ω-unsaturated aldehydes. Intramolecular cycloaddition, followed by reductive opening of the isoxazolidine ring, produced five- and seven-membered ring compounds with chiral hydroxy and amine functionalities of high enantiomeric purity in excellent yield.",10.1002/(sici)1099-0690(199811)1998:11<2513::aid-ejoc2513>3.0.co;2-u,1998-11-01,0.5839319236585534
Tetrahedron,"Chemistry of lactones: A one step synthesis of α-phenyl-γ-benzylidene-Δα,β-butenolide",,10.1016/s0040-4039(00)72168-x,1975-01-01,0.5839308644005868
European Journal of Organic Chemistry,Total Synthesis of the Natural Herbicide MBH‐001 and Analogues,"The first total synthesis of the natural herbicide MBH‐001 ( 1 ) is reported. Structurally it is a 2‐methyloxazol‐5(2 H )‐one with a (1‐hydroxyethyl) substituent at the 2‐position. By relying on cyclic nitrones, a flexible route to MBH‐001 and relevant analogues was developed. Key steps include the reaction of a 2‐hydroxyimino ester with an aldehyde to form a 5‐oxo‐2,5‐dihydrooxazole 3‐oxide. In an aldol‐type reaction, the anion of these cyclic nitrones reacted with an aldehyde at the 2‐position. A final reduction of the nitrone to the corresponding imine using zinc led to the target compounds. The cyclic nitrones are also accessible by reacting an α‐keto acid with an oxime. These two versatile synthetic routes enabled us to prepare the first MBH‐001 analogues for structure activity relationship analysis of the herbicidal efficacy. Thus, furthering our aim of developing new herbicides to tackle the ever‐growing problem of weed resistance.",10.1002/ejoc.202000294,2020-03-11,0.5839290663547543
Tetrahedron,Total synthesis of isoprostanes via the two-component coupling process,,10.1016/s0040-4039(02)00898-5,2002-05-01,0.583926153767581
Tetrahedron,Multi-gram synthesis of a nucleotide-competing reverse transcriptase inhibitor,,10.1016/j.tetlet.2013.01.129,2013-02-08,0.5839226867902794
Angewandte Chemie International Edition,Asymmetric Synthesis of the 1‐<i>epi</i> Aglycon of the Cripowellins A and B,"The unusual [5.3.2]bicyclic structure of the insecticidal Amaryllidaceae alkaloids cripowellins A and B has been synthesized for the first time by a sequence of Sharpless dihydroxylation, ring-closing metathesis (RCM), and intramolecular Heck reaction (see scheme). The asymmetric synthesis of the 1-epi aglycon proceeds with virtually complete diastereo- and enantioselectivity (≥98 % de, ≥98 % ee) in 13 steps and an overall yield of 5.6 %.",10.1002/anie.200500556,2005-05-13,0.5839102390629434
Tetrahedron,One-step conversion of terminal acetylenes into terminally functionalized (E)-3-methyl-2-alkenes via zircomium-catalyzed carboalumination. A simple and selective route to terpenoids,,10.1016/s0040-4039(01)94773-2,1978-01-01,0.5839088319301996
Synthesis,"A New Synthetic Route to 4-Alkyl-2<i>H</i>-1,4-thiazin-3- ones from 2-Methylthiazole",,10.1055/s-1979-28642,1979-01-01,0.5838967839503328
Tetrahedron,An efficient synthesis of N-hydroxy-α-amino acid derivatives of high optical purity,,10.1016/s0040-4039(00)95329-2,1987-01-01,0.5838920149145569
European Journal of Organic Chemistry,Stereoselective Synthesis of Tricyclic Diproline Analogues that Mimic a PPII Helix: Structural Consequences of Ring‐Size Variation,"Abstract Polycyclic proline‐derived scaffolds (ProMs) have recently demonstrated their value as conformationally defined dipeptide analogs for the modular construction of secondary structure mimetics, specifically interfering with PPII helix‐mediated protein–protein interactions. We disclose the stereoselective synthesis of two new tricyclic amino acid scaffolds (ProM‐4 and ProM‐8) that differ from the first generation scaffold ProM‐1 by the size of ring A. Conformational preferences and subtle structural differences of the three homologous scaffolds were analyzed by X‐ray crystallography, computational calculations, and NMR spectroscopy. N ‐ tert ‐butoxycarbonyl(Boc)‐3‐(1‐propenyl)azetidine‐2‐carboxylic acid was prepared from L ‐aspartic acid through β‐lactam intermediates. The corresponding piperidine‐based building block rac ‐ N ‐Boc‐3‐vinylpipecolic acid was synthesized by Cu‐catalyzed 1,4‐addition of vinyl‐MgBr to methyl N ‐Boc‐2,3‐dehydropipecolate. Target molecules were prepared through peptide coupling of the respective ring A building blocks with cis ‐5‐vinylproline tert ‐butyl ester and subsequent ring‐closing metathesis. Selective deprotection of a tert ‐butyl carbamate ( N ‐Boc protecting group) in the presence of a tert ‐butyl ester was achieved with trifluoroacetic acid at 0 °C.",10.1002/ejoc.201402737,2014-08-29,0.5838897797462616
Organic Process Research & Development,"Efficient Large-Scale Synthesis of 4-Phenyl-3-butyn-2-one, a Key Intermediate for a Novel Potent Adenosine Antagonist","Phenylacetylenic Grignard reagent reacts with acetic anhydride under mild conditions to give 4-phenyl-3-butyn-2-one in high yield. This method was applicable to a large-scale synthesis, and optimized reaction conditions have been investigated.",10.1021/op9700486,1998-01-01,0.5838885323800328
Organic Letters,Total Synthesis of Brevianamide S,"High Resolution Image Download MS PowerPoint Slide The first total synthesis of the alkaloid brevianamide S has been achieved in eight steps. This natural product, isolated from Aspergillus versicolor, exhibits selective antibacterial activity against Bacille Calmette-Guérin (BCG), a commonly used surrogate for Mycobacterium tuberculosis . Brevianamide S is proposed to act through a novel, yet-to-be-elucidated mechanism, making it a promising lead in the development of next-generation antitubercular agents. Our approach employs a bidirectional synthetic strategy, involving a bespoke alkenyl–alkenyl Stille cross-coupling reaction and a double aldol condensation. This represents a flexible and efficient platform for the future synthesis of structurally diverse analogues.",10.1021/acs.orglett.5c00860,2025-03-28,0.5838840596843887
Journal of Organic Chemistry,First Synthesis of Caerulomycin B. A New Synthesis of Caerulomycin C,"Caerulomycins produced by Streptomyces caeruleus are bipyridinic molecules endowed with antibiotic properties. The first synthesis of caerulomycin B (1) as well as a new synthesis of caerulomycin C (2) are reported. Starting from 3-hydroxypyridine, the same methodology was used to prepare both compounds 1 and 2. Efficiently controlled reactions such as metalation to allow the synthesis of 2,6-diiodo-3,4-dialkoxypyridines, which are key intermediates, and further halogen-lithium exchange and cross-coupling to reach the targets molecules 1 and 2 have been developed.",10.1021/jo010913r,2002-04-23,0.5838817440443677
Journal of the American Chemical Society,"Efficient Synthesis of Methylenebis(phosphonate) Analogues of P<sup>1</sup>,P<sup>2</sup>-Disubstituted Pyrophosphates of Biological Interest. A Novel Plausible Mechanism","Synthesis of novel nucleoside bicyclic trisanhydrides 7 in the reaction of nucleoside-5‘-methylenebis(phosphonate)s ( 4 ) with DCC is described. They were obtained by P 1,P 3 - and P 2,P 4 -dehydration of initially formed P 1, P 2, P 3, P 4 -bismethylenetetraphosphonate 6 . Reaction of 7 (N = 2‘,3‘- O -isopropylideneadenosin-5‘-yl) with 2‘,3‘- O -isopropylidenetiazofurin gave, after hydrolysis and deisopropylidenation, β-methylene-TAD ( 10a ), the known potent inhibitor of inosine monophosphate dehydrogenase (IMPDH). Similar reaction of 7 with benzyl 2,3- O -isopropylidene-β- d -riboside followed by hydrolysis and deprotection afforded a new methylenebis(phosphonate) analogue of ADP-ribose 10b. Upon reaction of 7 with riboflavin, the corresponding β-methylene-FAD ( 10c ) was obtained. Bicyclic trisanhydride 7 prepared from (2‘,3‘- O -isopropylidene- N 4 -acetylcytidin-5‘-yl)methylenebis(phosphonate) was used in the synthesis of the methylenebis(phosphonate) analogues of CDP-ethanolamine 10d and CDP-dipalmitoylglycerol 10e .",10.1021/ja964058i,1997-04-01,0.5838811934143945
Organic Letters,Total Synthesis of Diospyrodin and Its Three Diastereomers,"Antibacterial diospyrodin ( 1 ) was synthesized in 13 steps. Et 3 B and O 2 promoted the formation of an α - alkoxy carbon radical from l -ribose-derived α-alkoxyacyl telluride 5, which reacted with d -glucose-derived aldehyde 4 . The radical addition realized the convergent assembly of the contiguously hydroxylated carbon-chain of 3-α and greatly contributed to streamlining the synthetic route. Compound 3-α was transformed not only to 1 but also to its three diastereomers by functional group manipulations.",10.1021/acs.orglett.0c02280,2020-08-06,0.5838780545955337
Tetrahedron,"Synthesis of chiral 1,6,8-trioxoperhydropyrazino[1,2-c]-pyrimidines as novel highly functionalized scaffolds for peptidomimetics",,10.1016/s0040-4039(02)00964-4,2002-07-01,0.5838778700102254
Journal of Organic Chemistry,Diastereoselective Synthesis of Substituted Morpholines from <i>N</i>-Tethered Alkenols: Total Synthesis of (±)-Chelonin A,Intramolecular cyclization of nitrogen tethered alkenols catalyzed by palladium chloride leads to substituted morpholines in good yields. The methodology was used for the total synthesis of (±)-chelonin A.,10.1021/acs.joc.6b02260,2017-01-05,0.583877627126128
Synthesis,An Efficient and Convenient Synthesis of 2-Mercaptobenzaldehyde,All articles of this category An efficient and convenient synthesis of 2-mercaptobenzaldehyde (1) is described.,10.1055/s-1989-28357,1989-01-01,0.5838771774171413
Tetrahedron,New stereospecific synthesis of chiral thioacetal monosulfoxides,,10.1016/s0040-4039(01)95081-6,1978-01-01,0.583874182017861
Tetrahedron,A novel stereoselective total synthesis of (±)-hirsutene from saligenin,,10.1016/s0040-4039(01)02183-9,2002-01-01,0.5838672694614966
Tetrahedron,A stereoselective total synthesis of the novel sesquiterpene kelsoene,,10.1016/s0040-4039(99)00901-6,1999-06-01,0.5838672694614966
Tetrahedron,A stereoselective total synthesis of the novel triquinane sesquiterpene cucumin E,,10.1016/s0040-4039(01)00051-x,2001-03-01,0.5838672694614966
Journal of Organic Chemistry,Stereoselective Synthesis of (+)-Loline Alkaloid Skeleton,"The loline alkaloids present a compact polycyclic pyrrolizidine skeleton and contain a strained five-membered ethereal bridge, structural features that have proven challenging for synthetic chemists to incorporate since the discovery of this natural product family more than 100 years ago. These alkaloids are produced by mutualistic fungal symbionts (endophytes) living on certain species of pasture grasses and protect the host plant from insect herbivory. The asymmetric total synthesis of loline alkaloids is reported and extends our first-generation (racemic) synthesis of this alkaloid family. Key to the synthesis is a diastereoselective tethered aminohydroxylation of a homoallylic carbamate function and a Petasis Borono-Mannich addition.",10.1021/jo502493e,2015-01-22,0.5838645699196122
Synthesis,Synthesis of (–)- and (+)-Gummiferol via Asymmetric Synthesis of Glycidic Amides,An efficient synthesis of the natural product (–)-gummiferol is achieved according to a novel asymmetric methodology of epoxide formation based on a new class of chiral sulfonium salts. This new methodology allows the rapid and efficient construction of the diepoxide system contained within the natural product.,10.1055/s-0035-1561606,2016-04-18,0.5838638705373133
Synthesis,Synthesis of All Possible Stereoisomers of α-Branched [2.2]Paracyclophanylalkylamines,"The synthesis of all four possible stereoisomers of enantiopure and diastereomerically pure or highly enriched α-branched [2.2]paracyclophanylalkylamines is described. Key step is the nucleophilic 1,2-addition of alkyllithium reagents to hydrazones of 4-formyl[2.2]paracyclophane derived from the chiral auxiliaries SAMP/RAMP and RAMBO/SAMBO via chromatographic epimer separation. Reductive N-N bond cleavage of the resulting hydrazines, followed by treatment with benzyloxycarbonyl chloride afforded the N-Cbz-protected diastereo- and enantiopure (de, ee ÷ 99%) or diastereomerically enriched (de = 89-96%) title amines.",10.1055/s-2008-1042941,2008-04-01,0.5838631941499275
Journal of Organic Chemistry,"Total Synthesis of <i>d</i>,<i>l</i>-Isospongiadiol:  An Intramolecular Radical Cascade Approach to Furanoditerpenes","A stereoselective oxidative free-radical cyclization of beta-keto ester polyenes 7 and 19 has been accomplished as a one-step entry to the tricarbocyclic synthons 8and 21 which contain five and six stereogenic centers, respectively. These key synthons possessing an axial carboethoxy group at C-4 were ultimately converted to the spongian skeleton (8--> 14 and 21 --> 25 -->14). The synthesis of d,l-isospongiadiol (3) from the common intermediate 14 was realized after introduction of the 2alpha-hydroxy group in the spongian A-ring via epoxidation of silyl enol ether 28 and subsequent desilylation.",10.1021/jo951581r,1996-01-01,0.5838601484384132
Tetrahedron,"Enantioselective synthesis of 5-substituted α,β-unsaturated δ-lactones: application to the synthesis of styryllactones",,10.1016/s0040-4039(99)02050-x,2000-01-01,0.5838592530253167
Journal of the American Chemical Society,"A Two-Step, Formal [4 + 2] Approach toward Piperidin-4-ones via Au Catalysis","An efficient, formal [4 + 2] synthesis of synthetically valuable piperidin-4-ones from secondary amines in two steps has been achieved via a key gold catalysis without the purification of tertiary amine intermediates. This reaction is selective toward the less-substituted alkyl group and shows moderate to excellent diastereoselectivities. Its synthetic potential in alkaloid synthesis is demonstrated in a highly diastereoselective synthesis of (+/-)-cermizine C.",10.1021/ja903531g,2009-06-03,0.583851193423007
Synthesis,Synthesis of Linearly and Angularly Fused Indane-Based Constrained α-Amino Acid Derivatives,"The benzocyclobutene-based alpha-amino acid derivative, ethyl 5-acetamido-2,4,5,6-tetrahydro-1H-cyclobuta[f] indene-5-carboxylate is synthesized via coupling of a benzocyclobutene-derived dibromide with ethyl isocyanoacetate as the key step, followed by hydrolysis and subsequent acetylation. This methodology is generalized in order to prepare various linearly and angularly fused indane-based alpha-amino acid derivatives.",10.1055/s-0030-1260145,2011-08-02,0.5838502920676766
European Journal of Organic Chemistry,"Influence of A<sup>1,3</sup> Strain on the Stereochemical Outcome of Acid‐Mediated Amido Cyclization in the Synthesis of 2‐(4‐Methoxyphenyl)‐3,4‐(dihydroxy)piperidines","Abstract The synthesis of 2‐(4‐methoxyphenyl)‐3,4‐(dihydroxy)piperidines was accomplished by using ethyl p ‐methoxycinnamate as the starting material and an acid‐mediated amido cyclization reaction as the key step. This short and straightforward strategy avoids extra steps to create the chiral center and does not require a leaving group at the benzylic carbon. This study also showed that the stereochemical outcome of the cyclization reaction is influenced more by allylic 1,3‐strain (A 1,3 strain) than by the participation of a neighboring group.",10.1002/ejoc.201501577,2016-02-19,0.5838489240992825
Organic Letters,Synthesis of Multisubstituted Pyridines by Heterocyclization of TosMIC Derivatives: Total Synthesis of Caerulomycins A and K,"A concise synthesis of multisubstituted pyridines from α-allylic TosMIC derivatives and electrophiles is reported. The process involves a tandem heterocyclization exploiting the dual reactivity of the isocyanide group. The methodology tolerates various electrophiles, including halogen sources, and proceeds under mild conditions. Its utility is showcased in the total synthesis of caerulomycins A and K, in only five steps from TosMIC.",10.1021/acs.orglett.5c04454,2025-12-03,0.5838489183443065
Tetrahedron,Total synthesis of the esterase inhibitor (±)-ebelactone a using an aldol-claisen strategy,,10.1016/s0040-4039(00)88532-9,1990-01-01,0.5838468605762093
Tetrahedron,A novel route for the direct synthesis of secondary amides from aldehydes,,10.1016/s0040-4039(00)74340-1,1991-04-01,0.5838432081011922
Tetrahedron,A total synthesis of rac-patchouli alcohol,"A total synthesis of rac-patchouli alcohol (1) was achieved in six steps starting from 2,2,6-trimethylcyclohexadiene (2) using a vinyl radical cyclization strategy.",10.1016/0040-4039(95)01634-t,1995-10-01,0.5838408574697131
Synlett,Enamine-Based Domino Strategy for C-Acylation/Deacetylation of Acetoacetamides: A Practical Synthesis of β-Keto Amides,"A practical three-step route for C-acylation/deacetylation of acetoacetamides is described. Initial enamination of the acetoacetamides with Boc-monoprotected ethylenediamine provides β-enamino amides, which are acylated at the α-carbon with excellent selectivity. The C-acylated derivatives undergo domino fragmentation in acidic media to give the corresponding β-keto amides accompanied by 2-methyl-4,5-dihydro-1H-imidazole.",10.1055/s-0029-1219836,2010-04-16,0.5838401932670582
Tetrahedron,Preparation of new chiral pyrrolidinebisphosphines as highly effective ligands for catalytic asymmetric synthesis of R-(−)-pantolactone,,10.1016/s0040-4039(00)84983-7,1986-01-01,0.5838380424479344
Tetrahedron,A stereocontrolled synthetic route to anti -β-amino alcohols,,10.1016/s0040-4039(01)01611-2,2001-10-01,0.5838375943979016
Tetrahedron,"A new, stereoselective synthesis of methyl 1,2-trans-1-thioglycosides",,10.1016/s0040-4039(00)95930-6,1987-01-01,0.5838345131242031
Angewandte Chemie International Edition,Preparation of Optically Enriched Secondary Alkyllithium and Alkylcopper Reagents—Synthesis of (−)‐Lardolure and Siphonarienal,"Optically enriched secondary alkyl iodides were converted into secondary alkyllithium and secondary alkylcopper compounds with very high retention of configuration. Quenching with various electrophiles, including chiral epoxides, provided a range of chiral molecules with high enantiomeric purity (>90 % ee). This method has been applied in an iterative fashion in the total synthesis of (-)-lardolure in 13 steps and 5.4 % overall yield (>99 % ee, dr>99:1) and siphonarienal in 15 steps and 5.6 % overall yield (>99 % ee, dr>99:1) starting from commercially available ethyl (R)-3-hydroxybutyrate (>99 % ee).",10.1002/anie.201800792,2018-03-07,0.5838203546700507
Angewandte Chemie International Edition,Stereoselective Total Synthesis of (+)‐Giganin and Its C10 Epimer by Using Late‐Stage Lithiation–Borylation Methodology,"The first total synthesis of (+)-giganin and its unnatural diastereoisomer (+)-C10-epi-giganin has been completed in a total of 13 linear steps, and 7 % and 8 % overall yield, respectively (see scheme; (-)-sp= (-)-sparteine, (+)-sps=(+)-sparteine surrogate). Lithiation-borylation methodology has been successfully applied in the key step, to couple together advanced intermediates with very high diastereoselectivity, thus demonstrating its power as a tool for total synthesis.",10.1002/anie.201208403,2013-01-25,0.5838139064004283
Chemical Science,Topological self-template directed synthesis of multi-shelled intermetallic Ni <sub>3</sub> Ga hollow microspheres for the selective hydrogenation of alkyne,"hollow microspheres, and is expected to open up new opportunities for rational design and preparation of novel structured and highly efficient intermetallics.",10.1039/c8sc03178a,2018-10-19,0.5838134183927118
Journal of Organic Chemistry,"One-Pot Synthesis of Enantiopure Spiro[3,4-dihydrobenzo[<i>b</i>][1,4]oxazine-2,3′-oxindole] via Regio- and Stereoselective Tandem Ring Opening/Cyclization of Spiroaziridine Oxindoles with Bromophenols","A highly efficient regio- and stereoselective spiroaziridine ring opening with 2-bromophenols and a subsequent tandem cyclization reaction was developed for the one-pot synthesis of enantiopure 3,4-dihydrospiro[benzo[ b ][1,4]oxazine-2,3′-oxindole] with excellent enantiopurity (ee up to >99%). It is further extended to asymmetric synthesis of NH-free 3,4-dihydrospiro[benzo[ b ][1,4]oxazine-2,3′-xindole] retaining the optical activity .",10.1021/acs.joc.9b01611,2019-07-16,0.5838130317460166
European Journal of Organic Chemistry,"Synthesis of Symmetrical Dodeco‐6,7‐diuloses","Dodeco‐6,7‐diuloses represent a rare class of sugars and can be considered as anomerically linked di‐hexoses with two hemiacetal functions in the middle. Herein, the synthesis of three symmetrical dodeco‐6,7‐diuloses ( gluco ‐ gluco, galacto ‐ galacto, manno ‐ manno ) is described. For their preparation four synthetic strategies were pursued, whose mutual key step, the connection of the anomeric centers, is particularly emphasized. Specifically, C–C bond forming methods are employed, such as a Grubbs metathesis, a stannyl glycal homocoupling reaction, a coupling of a sulfinyl glycal with a sugar lactone and a Ramberg–Bäcklund rearrangement. Since the ring closure via hemiacetal formation of the target compounds cannot be predicted, intensive NMR spectroscopic structure elucidation of the diuloses was performed.",10.1002/ejoc.202000615,2020-05-16,0.5838108622998958
Organic Letters,Synthesis of the Cyclohepta[<i>e</i>]hydrindane Core of the Marine Homoverrucosane Diterpenoid Gagunin E,"The synthesis of the A-B-cis B-C-trans annulated cyclohepta[e]hydrindane core of gagunin E with a fully elaborated B-C ring segment has been achieved. Using an adaptable A ring building block, the B ring was annulated by (4 + 2)-cycloaddition and the C ring by ring-closing metathesis. The angular methyl groups were attached by electrophilic cyclopropanation-ring opening.",10.1021/acs.orglett.6b03799,2017-01-27,0.583796850787122
Tetrahedron,A free radical route to syn lactones and other prostanoid intermediates in isoprostaglandin synthesis.,,10.1016/s0040-4039(00)61401-6,1993-12-01,0.5837793841033199
Tetrahedron,"Synthesis of new chiral 1,3-aminoalcohols derived from levoglucosenone and their application in asymmetric alkylations",,10.1016/j.tetlet.2015.04.051,2015-04-17,0.5837748902040613
Organic Process Research & Development,"A Practical, Kilogram-Scale Implementation of the Wolff−Kishner Reduction",A safe and practical strategy has been developed for the large-scale preparation of imidazole 7 . The key transformation involved the Wolff−Kishner reduction of the sterically demanding neopentyl-trifluoromethylcyclopropyl imidazole ketone 8 . The described process provided the desired product in 74% overall yield without recourse to chromatographic purification. Safety considerations which allowed for the reaction to be conducted safely on kilogram scale are discussed.,10.1021/op9000274,2009-04-06,0.5837708735781388
Organic Process Research & Development,Development of a Scalable Route for a Key Thiadiazole Building Block via Sequential Sandmeyer Bromination and Room-Temperature Suzuki–Miyaura Coupling,"To avoid the use and handling of Lawesson’s reagent or other thiation agents in the in-house kilolab, a new scalable route to ethyl 5-(2,4-difluorophenyl)-1,3,4-thiadiazole-2-carboxylate ( 1 ) was developed. The key to success was the use of a commercially available amino-thiadiazole building block, which was converted into the desired product via a sequence of Sandmeyer bromination and Suzuki–Miyaura coupling. The different parameters of the Pd-catalyzed coupling have been studied in detail and allowed the reaction to be performed under mild conditions at room temperature and with low catalyst loading. The inconsistencies of the initial scale-up runs with regard to the sluggish conversion of the Suzuki–Miyaura coupling due to Cu contamination were addressed, and the findings were directly implemented in the subsequent batches, which finally led to an improved overall understanding and robustness of the process.",10.1021/acs.oprd.9b00495,2020-01-28,0.583768656839506
Journal of Organic Chemistry,"Preparation and Diastereoselective Birch Reduction−Alkylation of Chiral 3,4-Dihydro-1(2<i>H</i>)-isoquinolinones. Enantiospecific Syntheses and Opioid Receptor Affinities of Several Hydro-2,3- dimethyl-1<i>H</i>-7,12<i>a</i>-methanobenzo[6,7]cycloocta[1,2-<i>c</i>]pyridine-9-ols","Synthetic procedures have been developed to provide 2,3-disubstituted-3,4-dihydro-1(2 H )-isoquinolinones 6, 10, and 15 from (1 R,2 S )-ephedrine, (1 R,2 R )-pseudoephedrine, and l -phenylalanine. Birch reduction of 6 and 10 gave enantiomerically related lactam enolates that were alkylated with methyl iodide, allyl bromide, benzyl bromide, p -benzyloxybenzyl bromide, and p -methoxybenzyl bromide to give 7a − 7e, 11a, and 11b with diastereoselectivities > 20:1. Birch reduction−methylation of 15 gave 19 with a diastereoselectivity of >35:1. Selective reduction of the disubstituted double bond in 19 with diimide and cleavage of the tert -butyldimethylsilyl ether gave 20b, from which iodoetherification under thermodynamic control gave the iodopyran 21a; iodoetherification of 20b under kinetic control gave the iodotetrahydrofuran 22 . Enantiospecific syntheses of analogues of 24 (Schultz, A. G.; Kirincich, S. J.; Rahm, R. Tetrahedron Lett . 1995, 36, 4551−4554) have been developed. Tetracycle 24 is isomeric with the potent analgesic agent levorphanol, but the bridging of the hydroisoquinoline ring by the hydroxybenzyl unit in 24 is at C(7, isoquinoline numbering) and C(8a) rather than at C(1) and C(4a) as in levorphanol. The key step in the transformation of 7d and 7e to tetracyclic phenolic amines (−)- 26 and (+)- 28 is the Grewe-type cyclization of 7d to 25b and 7e to 25c . K i values for the inhibition of binding to the μ-, δ-, and κ-opioid receptors by (−)- 26, (+)- 26, (+)- 28, (−)- 28, and (+)- 32 are reported.",10.1021/jo980921g,1998-10-01,0.583767237184585
Synlett,"Asymmetric Synthesis of (+)-CP-99,994 and (+)-L-733,060 from Enantiomerically Pure (3<i>S</i>,4<i>S</i>)-4-(<i>tert</i>-Butylcarbamoyl)-4-phenyl-1-buten-3-ol","Asymmetric syntheses of neurokinin substance P receptor antagonists (+)-CP-99,994 and (+)-L-733,060 have been accomplished starting from enantiomerically pure (3S,4S)-4-(tert-butylcarbamoyl)-4-phenyl-1-buten-3-ol.",10.1055/s-2006-956453,2006-12-01,0.583764704643416
Tetrahedron,Carbolithiation of vinyl pyridines as a route to 7-azaindoles,,10.1016/j.tetlet.2005.01.046,2005-01-29,0.583763325970159
Organic Letters,Synthesis of 5-Methylene-2-pyrrolones,"A facile, one-pot synthetic method for the synthesis of 5-methylene-2-pyrrolones (5MPs) from inexpensive furfuryl acetate is described. Bromine oxidation and trapping of the in situ generated 1,4-dicarbonyl compound by a primary amine provided the corresponding 5MPs in 50-69% yield.",10.1021/acs.orglett.8b02030,2018-07-31,0.583760724902287
Synthesis,A New Short and Efficient Route to 3-Deoxy-<scp>d</scp>-<i>manno</i>-oct-2-ulosonic Acid (KDO) and 3-Deoxy-<scp>d</scp>-<i>arabino</i>-hept-2-ulosonic Acid (DAH),"An efficient synthesis of lactones 5 and 6, known intermediates towards KDO and DAH, respectively, has been achieved by a short and highly efficient route. Homologation of protected d-mannose and d-arabinose was performed by a Peterson reaction with 2-lithio-2-trimethylsilyldithiane or the corresponding bis(methylsulfanyl­) derivative, followed by the cyclization of the resulting ketene dithioacetal under very smooth conditions. An oxidative treatment with iodine gave the lactones 5 and 6 in a three-step sequence with high yields. Interestingly, this approach can be considered as a general method for the synthesis of various 2-deoxy­sugar lactones.",10.1055/s-2006-926375,2006-01-01,0.5837586608336781
Organic Letters,Short Synthesis of Berkeleyamide D and Determination of the Absolute Configuration by the Vibrational Circular Dichroism Exciton Chirality Method,"The first synthesis of (±)-berkeleyamide D has been accomplished. The key features of this synthesis include the formation of an α,β-epoxy-γ-lactam via a Darzens reaction and the construction of a spirocyclic ring system by a C-acylation reaction followed by an intramolecular spirocyclization via an epoxide-opening reaction. Following optical resolution by chiral HPLC, the absolute configurations of both enantiomers of berkeleyamide D were determined by the vibrational circular dichroism exciton chirality method.",10.1021/ol500148g,2014-02-14,0.5837573518635835
Journal of Organic Chemistry,"Fluoride-Mediated Elimination of Allyl Sulfones: Application to the Synthesis of a 2,4-Dimethyl-A-ring Vitamin D<sub>3</sub> Analogue","A coupling strategy for the synthesis of 2,4-dimethyl-1α,25(OH)(2)D(3) is achieved which involves methylation of a pro-A ring vinyl sulfone and in situ traping of the allyl sulfonyl anion with a CD ring allyl chloride. TBAF-promoted 1,2-eliminative desulfonylation and concomitant silyl ether deprotection gives the vitamin D(3) analogue.",10.1021/jo300672a,2012-04-25,0.5837567953689461
Angewandte Chemie International Edition,The Total Synthesis of (−)‐Nitidasin,"Nitidasin is a pentacyclic sesterterpenoid with a rare 5-8-6-5 carbon skeleton that was isolated from the Peruvian folk medicine ""Hercampuri"". It belongs to a small class of sesterterpenoids that feature an isopropyl trans-hydrindane moiety fused to a variety of other ring systems. As a first installment of our general approach toward these natural products, we report the total synthesis of the title compound. Our stereoselective, convergent route involves the addition of a complex alkenyl lithium compound to a trans-hydrindanone, followed by chemoselective epoxidation, ring-closing olefin metathesis, and redox adjustment.",10.1002/anie.201403605,2014-06-24,0.5837492704887551
Synlett,"4-Ethoxy-1,1,1-trifluoro-3-buten-2-one (ETFBO), a Versatile Precursor for Trifluoromethyl-Substituted Heteroarenes – a Short Synthesis of Celebrex® (Celecoxib)","4-Ethoxy-1,1,1-trifluoro-3-buten-2-one (ETFBO) serves as a trifluoromethyl-containing building block for the preparation of trifluoromethyl-substituted thiophenes, furans, pyrrols, and piperazines. Key steps are an addition–elimination reaction to ETFBO followed by the thiazolium-catalyzed Stetter reaction. The scope of this chemistry was demonstrated in a new synthetic approach towards the COX-2 selective, nonsteroidal anti-inflammatory drug Celebrex® (celecoxib).",10.1055/s-0036-1589097,2017-08-22,0.5837412464175125
Synlett,First Stereoselective TotalSynthesis of Sporostatin and Determination of AbsoluteConfiguration,"The first simple and efficient total synthesis of sporostatin has been accomplished in five steps starting from (S)-propylene oxide. The synthesis utilizes simple reactions such as esterification, cross-metathesis, and intramolecular Friedel-Crafts reaction as key steps.",10.1055/s-0028-1087956,2009-02-25,0.5837404513259947
Tetrahedron,A new approach to the synthesis of ?-methylene-?-hydroxy-?-butyrolactones,,10.1016/s0040-4039(00)78385-7,1994-10-10,0.5837349909272616
Tetrahedron,A new approach to the synthesis of -methylene--hydroxy--butyrolactones,,10.1016/0040-4039(94)80011-1,1994-10-01,0.5837349909272616
Angewandte Chemie International Edition,Total Synthesis of (+)-Epoxyquinols A and B,"A highly stereoselective HfCl4-mediated Diels–Alder reaction of furan and the chiral acrylate ester of Corey's auxiliary to subsequently give 1, and the realization of the postulated biosynthetic pathway for the construction of epoxyquinols A and B, namely, oxidative 6π electrocyclization, followed by Diels–Alder reaction of the unprotected monomer are the key steps in the asymmetric total synthesis of (+)-epoxyquinols A and B.",10.1002/1521-3773(20020902)41:17<3192::aid-anie3192>3.0.co;2-e,2002-09-02,0.5837332127652719
Angewandte Chemie International Edition,In Situ Inhibitor Synthesis and Screening by Fluorescence Polarization: An Efficient Approach for Accelerating Drug Discovery,"Target-directed dynamic combinatorial chemistry has emerged as a useful tool for hit identification, but has not been widely used, in part due to challenges associated with analyses involving complex mixtures. We describe an operationally simple alternative: in situ inhibitor synthesis and screening (ISISS), which links high-throughput bioorthogonal synthesis with screening for target binding by fluorescence. We exemplify the ISISS method by showing how coupling screening for target binding by fluorescence polarization with the reaction of acyl-hydrazides and aldehydes led to the efficient discovery of a potent and novel acylhydrazone-based inhibitor of human prolyl hydroxylase 2 (PHD2), a target for anemia treatment, with equivalent in vivo potency to an approved medicine.",10.1002/anie.202211510,2022-09-16,0.5837260693464523
Synthesis,A One-Step Synthesis of 3-Nitroflavanones and their Conversion to 3-Nitroflavones,,10.1055/s-1981-29402,1981-01-01,0.583720566308726
Synthesis,Two Novel and Simple Approaches to ‘CD45 Protein Tyrosine Phosphatase Inhibitor’ (Z)-Pulchellalactam and Derivatives,"Two novel routes to the naturally occurring CD45 protein tyrosine phosphatase inhibitor, ( Z )-pulchellalactam, and its derivatives are reported in two steps starting from dienoic acids through electrophilic cyclisation. This methodology proceeds regio- and stereoselectively, and can be used to design a library of synthetic pulchellalactam analogues.",10.1055/s-0035-1561375,2016-02-16,0.5837203575987363
Organic Letters,A Facile Synthetic Route to a Third-Generation Dendrimer with Generation-Specific Functional Aryl Bromides,"The synthesis of three third-generation dendrimers that selectively carry one aryl bromide functional group in the first, second, or third generation, respectively, is described. These functions, regardless of their location, can be chemically modified by Suzuki cross-coupling chemistry with p-tert-butylbenzene boronic ester.",10.1021/ol005972q,2000-05-06,0.583715882825786
Organic Process Research & Development,"Selective Hydrolysis of Ethyl 5,6-Dihydro-4H-pyrrolo[1,2-<i>b</i>]pyrazole-2-carboxylate and Ethyl 5,6-Dihydro-4H-pyrrolo[1,2-<i>b</i>]pyrazole-3-carboxylate as a Key Step in the Large-Scale Synthesis of Bicyclic Heteroaryl Carboxyaldehydes","The isomeric mixture of ethyl 5,6-dihydro-4H-pyrrolo[1,2- b ]pyrazole-2- and −3-carboxylates ( 14 and 15 ), derived from a proline meso-ionic synthon, demonstrated remarkably different stabilities towards alkaline hydrolysis. On that basis, a nonchromatographic, highly efficient method for their large-scale separation was developed. The desired isomer 14 was converted into 5,6-dihydro-4H-pyrrolo[1,2- b ]pyrazole-2-carbaldehyde, a key intermediate in the synthesis of bicyclic heteroaryl-substituted 6-alkylidene penems.",10.1021/op050218b,2006-06-02,0.5837099778714073
Synthesis,"Chemistry of 3-Hydroxypyridine Part 4: Synthesis of 2- and 2,3-Substituted 5-[Fluoro(chloro)alkoxy]pyridines via 5-Hydroxy-2-(4-nitrophenylazo)pyridines","All articles of this category The preparation of 2-amino-, hydroxy- and 2,3-dihalo-substituted 5-[fluoro(chloro)alkoxy]pyridines via 5-hydroxy-2-(4-nitrophenylazo)pyridines prepared from commercially available 3-hydroxypyridines are described.",10.1055/s-1990-26980,1990-01-01,0.5837087262240536
Angewandte Chemie International Edition,"Biomimetic Syntheses of (±)‐Isopalhinine A, (±)‐Palhinine A, and (±)‐Palhinine D","Abstract The first total synthesis of isopalhinine A, as well as unified syntheses of palhinine A and palhinine D, were successfully accomplished by means of a biomimetic strategy that proceeds through a bioinspired 5/6/6/9 tetracyclic intermediate, which mimics the amino ketone form of palhinine D. An early‐stage direct S N 2 cyclization to construct the nine‐membered azonane ring minimized the transannular strain that would otherwise be increased by the twisted nature of the isotwistane skeleton. Then, a diastereoselective Diels–Alder reaction of a masked ortho ‐benzoquinone using the nine‐membered ring as a steric shielding group furnished a functionalized 6/6/9 tricyclic skeleton and established the desired stereochemistry at the C3, C7, C12, and C15 positions in one step. A thiol‐mediated acyl radical cyclization gave the bioinspired intermediate bearing three differentiated oxygen‐containing functional groups, from which all three total syntheses could be completed in either two or three additional steps.",10.1002/anie.201809130,2018-10-05,0.5837062629535636
Synlett,"Integrated Synthesis of Thienyl Thioethers and Thieno[3,2-b]thiophenes via 1-Benzothiophen-3(2H)-ones","Abstract A one-pot procedure for the synthesis of thienyl thioethers is described. Several thienyl thioethers were synthesized by a TfOH-promoted Friedel–Crafts-type cyclization, a subsequent nucleophilic attack by an arenethiol, and dehydration. This protocol was successfully applied to the synthesis of thienoacene derivatives by using a Pd-catalyzed dehydrogenative cyclization.",10.1055/s-0040-1707280,2020-09-21,0.5837030141233397
Tetrahedron,Efficient diastereoselective synthesis of anti-α-bromo-β-hydroxyketones,,10.1016/s0040-4039(99)01640-8,1999-11-01,0.5837018707750073
Journal of Organic Chemistry,"TCP- and Phthalimide-Protected <i>n</i>-Pentenyl Glucosaminide Precursors for the Synthesis of Nodulation Factors As Illustrated by the Total Synthesis of NodRf-III (C18:1, MeFuc)","TCP- and phthalimide-protected n -pentenyl glucosaminide (NPG) precursors have been utilized in a convergent stereocontrolled synthesis of the nodulation factor NodRf-III (C18:1, MeFuc) produced by Rhizobium fredii USDA257, 2 . Nodulation factors are lipooligosaccharides that are secreted by bacteria which trigger the early steps in the formation of root nodules in leguminous plants. This symbiotic relationship between plant and bacteria plays a major role in the global nitrogen cycle. Key to our synthetic approach was the use of the TCP (tetrachlorophthaloyl) group to provide for N -differentiation of the linear glucosamine backbone and the use of FeCl 3 for the removal of benzyl protecting groups from the tetrasaccharide. The saccharide skeleton was assembled via the NPG-based coupling of a linear β(1→4) glucosamine disaccharide to a 6- O -fucosylated glucosamine acceptor. Significant yield enhancements for NPG couplings were observed at lower temperatures. Subsequent exchange of benzyl to tert -butyldimethylsilyl protecting groups via FeCl 3 mediation and installation of the fatty chain on the nonreducing terminus via selective removal of TCP led to a late intermediate which was deprotected in high yield to afford the natural product.",10.1021/jo962362o,1997-07-01,0.5837001969636614
Tetrahedron,"Selective synthesis of N-substituted pyrrolo[1,2-a]pyrazin-1(2H)-one derivatives via alkyne cyclization",,10.1016/j.tetlet.2014.10.044,2014-10-14,0.5836993816000614
Tetrahedron,A new synthesis of 2-amino-6-7-dihydroxy tetrahydronaphthalene (ADTN) via functionalized aryl-lithium reagents and methyl 2-trimethylsilylacrylate - a new annulation sequence,,10.1016/s0040-4039(01)81999-7,1981-01-01,0.5836988248382406
European Journal of Organic Chemistry,Efficient Diastereoselective Three‐Component Synthesis of Pipecolic Amides,"An efficient Ugi‐type three‐component reaction (U‐3CR) for the synthesis of pipecolic amides is reported. The U‐3CR between electronically diverse isocyanides, carboxylic acids and 4‐substituted Δ1‐piperideines proceeds in a highly diastereoselective fashion. The Δ1‐piperideines are obtained by NCS‐mediated oxidation of the corresponding 4‐substituted piperidines, which in turn are generated by an efficient two‐step procedure involving the alkylation of 4‐picoline and subsequent catalytic hydrogenation of the pyridine ring. We demonstrate the utility of this U‐3CR, in combination with the convertible isocyanide 2‐bromo‐6‐isocyanopyridine, in the synthesis of the anticoagulant argatroban.",10.1002/ejoc.201900399,2019-04-25,0.5836984195743254
Tetrahedron,Asymmetric synthesis with chiral hydrogenolysable amines. ω-imino esters reduction : a diastereoselective route to ω-alkyl lactams,,10.1016/s0040-4039(00)74246-8,1992-07-01,0.583697117429282
Organic Letters,Synthesis of the C(43)−C(67) Fragment of Amphidinol 3,"[reaction: see text] A synthesis of the C(43)-C(67) fragment of amphidinol 3 (AM3) has been accomplished by a route that features the use of a double allylboration reaction for synthesis of 1,5-diol 4b, which serves as a precursor to dihydropyran 11.",10.1021/ol052322j,2005-10-22,0.5836897182091089
Tetrahedron,"The first asymmetric total synthesis of (R)-tuberolactone, (S)-jasmine lactone and (R)-δ-decalactone",,10.1016/j.tetlet.2006.08.135,2006-09-29,0.5836892907937822
Journal of the American Chemical Society,"Ir-Catalyzed Double Asymmetric Hydrogenation of 3,6-Dialkylidene-2,5-diketopiperazines for Enantioselective Synthesis of Cyclic Dipeptides","An Ir/spiro[4,4]-1,6-nonadiene-based phosphine-oxazoline ligand (SpinPHOX) complex-catalyzed double asymmetric hydrogenation of 3,6-dialkylidene-1,4-dimethylpiperazine-2,5-diones has been developed, providing efficient and practical access to a wide variety of chiral 3,6-disubstituted-2,5-diketopiperazines in high yields with exclusive cis-diastereo- and excellent enantioselectivities (>99% de, up to 98% ee). The synthetic utilities of the protocol have been demonstrated in a gram scale synthesis of 6a and efficient construction of chiral products 8, 14, and 17 as well as a 2-butenyl-bridged bicyclic diketopiperazine 10 and hydroxydiketopiperazine 11. With an analogous achiral Ir catalyst, the hydrogenation of enantiopure monohydrogenated intermediate 7a gave cis-6a as the only product, indicating that the second-step hydrogenation of the titled transformation is a chiral substrate controlled process. The reaction profile study for asymmetric hydrogenation (AH) of 5a revealed that the concentration of the monohydrogenation intermediate 7a remained at a low level (<8%) during the course of hydrogenation. The hydrogenation of 5a to 6a proceeded significantly faster than that of its half-hydrogenated intermediate ( S)-7a, indicating that the titled reaction involves primarily a processive mechanism, in which a single catalyst molecule performs consecutive hydrogenation of the two C═C double bonds in substrate 5a without dissociation of the partially reduced 7a. The present protocol represents a rare example of asymmetric catalytic consecutive hydrogenation of heterocycles and provides an alternative way for efficient construction of cyclic dipeptides.",10.1021/jacs.9b02920,2019-05-12,0.5836871619733123
Tetrahedron,A new carbohydrate-based synthetic approach to trichothecenes. Synthesis of a bicyclic BC core of verrucarol from d-galactose,,10.1016/s0040-4039(01)01366-1,2001-09-01,0.5836865922239486
Tetrahedron,Convergent stereospecific total synthesis of monocillin I and radicicol: some simplifications and improvements,,10.1016/s0040-4039(02)00713-x,2002-05-01,0.5836811019241813
Synlett,"An Efficient Synthesis of Enantiomerically Pure (1<i>R</i>,2<i>S</i>,5<i>S</i>)- and (1<i>S</i>,2<i>R</i>,5<i>R</i>)-Rosaprostol Methyl Esters","We report a concise synthesis of the enantiomerically pure 1,2-trans-1,5-cis-methyl esters of rosaprostol, a prostaglandin derivative used for the treatment of gastric and duodenal ulcers, ­using as key step the chemo- and stereoselective Michael addition of a Grignard reagent to an unprotected hydroxycyclopentenone.",10.1055/s-2007-982558,2007-06-01,0.5836807005050262
Organic Letters,Total Synthesis of the Ambigols: A Cyanobacterial Class of Polyhalogenated Natural Products,The first total synthesis of all members of the cyanobacterial natural product class of the ambigols is described. Key steps of the synthetic strategy are the formation of sterically demanding mono- and bis-iodonium salts to install the required biaryl ether structural elements and Suzuki cross-coupling giving straightforward access to the biaryl bonds. The synthetic methods are also utilized to construct unnatural or hypothetical ambigols that are still awaiting discovery from Nature.,10.1021/acs.orglett.0c03784,2020-12-11,0.5836799452686398
Journal of Organic Chemistry,Synthesis of <i>ent</i>-Cleistanthane Diterpenoid Spruceanol: Construction of an Aromatic C Ring <i>via</i> Lewis Acid-Controlled Regioselective Diels–Alder Cycloaddition,"The first synthesis of ent -cleistanthane-type diterpenoid spruceanol with significant anticancer activity is described. A chiral pool approach was employed with a linear sequence of 13 steps beginning from readily available and inexpensive andrographolide. The approach features the construction of an aromatic ring with hydroxyl and methyl groups at C-12 and C-13 of the target compound, respectively, via Lewis acid-controlled regioselective Diels–Alder cycloaddition and the regioselective removal of the primary hydroxyl group of the Diels–Alder adduct.",10.1021/acs.joc.0c00713,2020-04-28,0.5836788106992505
Tetrahedron,"One pot, three-component synthesis of novel 3,4-dihydrophthalazin-2(1H)-yl-4-phenyl-4H-pyrans",,10.1016/j.tetlet.2014.02.020,2014-02-21,0.5836751986429835
European Journal of Organic Chemistry,"Total Synthesis of a Diarylheptanoid, Rhoiptelol B","Abstract A stereoselective total synthesis of rhoiptelol B has been accomplished for the first time. The four asymmetric centers were efficiently generated through Keck allylation, Jacobson epoxidation Aldol reaction and reductive etherification as the key steps.",10.1002/ejoc.200901041,2009-11-27,0.5836735392139969
Synlett,Practical Synthesis of the Fluorogenic Enzyme Substrate 4-Methylumbelliferyl α-l-Idopyranosiduronic Acid,"A practical and concise synthesis of 4-methylumbelliferyl α-l-idopyranosiduronic acid, a fluorogenic enzyme substrate diagnostic for α-l-iduronidase, was accomplished. It features successive radical bromination and radical reduction of easily accessible methyl 4-methyl­umbelliferyl-2,3,4-tri-O-acetyl-β-d-glucouronate in four steps with 28% overall yield.",10.1055/s-0040-1708021,2020-04-17,0.583669542231584
Journal of the American Chemical Society,Pyrazofurin Biosynthesis Involves Nonenzymatic Ring Contraction of a Pyridazine Intermediate Triggered by a Rieske Enzyme-Catalyzed Oxygenation,"-nucleosides, exhibiting antibacterial, antiviral, and antitumor activities. Despite previous studies elucidating the early biosynthetic steps of pyrazole formation, how the linear hydrazone intermediate is cyclized to a pyrazole ring remains unknown. Herein, substrate analogs are used to show that the amidohydrolase PyfA mediates intramolecular cyclization of 2-hydrazinylidenepentanedioic acid to yield a 4,5-dihydropyridazine ring, which can undergo PyfO-catalyzed dehydrogenation to generate a pyridazine product. More importantly, the Rieske enzyme PyfB is demonstrated to catalyze oxygenation of 4,6-dihydroxypyridazine-3-carboxylic acid. The resulting six-membered pyridazine product is found to undergo uncatalyzed rearrangement to the five-membered pyrazole ring. This work thus highlights a unique pyrazole-forming pathway involving a rare pyridazine intermediate that undergoes oxidation-triggered nonenzymatic ring contraction to yield the pyrazole core.",10.1021/jacs.5c15879,2025-10-29,0.5836634312602758
Tetrahedron,Synthesis of cis-3-hydroxypipecolic acid via SmI2-mediated cyclization of aldehydo β-aminovinyl sulfoxides,,10.1016/j.tetlet.2009.11.116,2009-11-30,0.5836572711751953
Tetrahedron,A novel general route to the synthesis of carboxylic acid esters and thiolesters,,10.1016/s0040-4039(00)73371-5,1994-06-01,0.5836544394880152
Tetrahedron,N-Methylative aziridine ring opening and asymmetric synthesis of MeBmt,,10.1016/j.tetlet.2011.08.048,2011-09-09,0.5836536992278193
Tetrahedron,"N-Methylative aziridine ring opening: asymmetric synthesis of hygroline, pseudohygroline, and hygrine",,10.1016/j.tetlet.2014.12.133,2015-01-02,0.5836536992278193
Synthesis,Synthesis and Use of a Phosphoramidite Ligand for the Copper-Catalyzed Enantioselective Allylic Substitution. Tandem Allylic Substitution/Ring-Closing Metathesis,"A new one-pot method of reductive amination is used to prepare a chiral C2 symmetrical amine. This amine is used for the synthesis of a new chiral phosphoramidite ligand. The new ligand is, in turn, used to illustrate the enantioselective copper-catalyzed allylic substitution with Grignard reagents. When a remote double bond is located on the Grignard reagent, the newly formed alkene undergoes an in situ ruthenium-catalyzed ring-closing metathesis to afford the cyclized product in 77% yield and 94% ee.",10.1055/s-2004-829188,2004-01-01,0.583649430206928
Organic Process Research & Development,Total Synthesis of Hematoporphyrin and Protoporphyrin: A Conceptually New Approach,"The total synthesis of protoporphyrin IX and its disodium salt using a new alternative method to the classical MacDonald condensation is reported. The key step is the reaction of the new unsymmetrical diiodo dipyrrylmethane 1 with the known dipyrrylmethane 2 . Coupling of the two fragments leads directly to porphyrin 3 without the need of an oxidizing agent. The new methodology is well suited for the synthesis of protoporphyrin IX derivatives on a multi 100 g scale in good quality without the need for chromatography. Furthermore, these preparations are completely free of any contaminant of animal origin, which represents a real improvement in the manufacturing of protoporphyrin IX derivatives.",10.1021/op100036c,2010-06-03,0.5836445806602424
Tetrahedron,"A stereoselective and efficient route to (3S, 4R, 5S)-(+)-4,5-dihydroxycyclopent-1-en-3-ylamine: the side chain of the hypermodified nucleoside Q",,10.1016/s0040-4039(98)01738-9,1998-10-01,0.583640779477578
Tetrahedron,Studies directed toward the synthesis of viridenomycin. Route 2: a second generation approach,,10.1016/s0040-4039(01)00701-8,2001-06-01,0.5836390502962079
Tetrahedron,Approaches to installing a N-gem-dimethylmethylene-2-oxazolyl group and application to the synthesis of a second generation HIV protease inhibitor,,10.1016/j.tetlet.2005.01.103,2005-02-11,0.5836371930853673
Tetrahedron,Synthesis of iboga alkaloids by Pd-catalyzed heteroannulation of 2-iodoaniline with an internal alkyne as the key step,,10.1016/j.tetlet.2010.01.037,2010-01-16,0.5836346097652361
European Journal of Organic Chemistry,Total Synthesis of (±)‐Quebrachamine via [3+2] Cycloaddition and Efficient Chloroacetamide Photocyclization,"Abstract The total synthesis of (±)‐quebrachamine has been completed in 13 linear steps and 17.8 % overall yield. The indole core was constructed via a formal [3+2] dipolar cycloaddition between a functionalized nitrile and donor‐acceptor cyclopropane, and the synthetically challenging nine‐membered ring was secured by an efficient chloroacetamide photocyclization.(© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2009)",10.1002/ejoc.200801154,2009-01-14,0.5836321120357011
Synlett,A Highly Efficient and Versatile Synthesis of d- and l-erythro-Sphinganine,"All articles of this category An expedient convergent synthesis of naturally occurring C 18 - erythro -sphinganine (dihydrosphingosine, 1 ) is presented. Chiral protected 2-amino-1,3,4-butanetriol 6 is readily transformed into oxazolinyl oxirane building block 9 , which is alkylated by a copper mediated S N 2 type nucleophilic substitution with tetradecylmagnesium chloride. This method promises to be suited for large-scale syntheses and for rapid access to sphinganine analogues modified in the backbone. amino alcohols - coupling - natural products - sphingolipids - stereoselective synthesis",10.1055/s-2001-18784,2001-01-01,0.5836316812537519
Tetrahedron,The synthesis and its ord and cd study of new steroidal heterocycles with a 4-oxoperhydropyridazine system fused to ring D,,10.1016/s0040-4039(00)90619-1,1967-01-01,0.5836309794600144
Journal of Organic Chemistry,Total Synthesis of the Cytotoxic Anhydrophytosphingosine Pachastrissamine (Jaspine B),"A short, 8-step synthesis of the marine natural product pachastrissamine has been developed that relies on a diastereoselective aldol reaction between a suitably protected hydantoin and an optically enriched α-chloroaldehyde. This synthetic route provides new opportunities for exploring structure activity relationships within this family of natural products.",10.1021/jo4013223,2013-08-06,0.5836283174645606
Journal of Organic Chemistry,Total Synthesis of Dihydroclerodin from (<i>R</i>)-(−)-Carvone,"The first total synthesis of the natural enantiomer of the insect-antifeedant dihydroclerodin ( 1 ) and lupulin C ( 40 ) has been achieved starting from ( R )-(−)-carvone ( 2 ). In the applied strategy, the hexahydrofuro[2,3- b ]furan moiety was introduced in an early stage of the synthesis. The correct configuration at C-9, C-11, C-13, and C-16 was established by application of a remarkably diastereoselective Mukaiyama reaction. The desired configuration at C-10 was obtained by catalytic reduction of the intermediate enone 21 . After annulation of the second ring, the structural features at C-4, C-5, and C-6 were introduced. The successful finishing of the synthesis included a Chugaev elimination to give the exocyclic double bond at C-4 that is present in lupulin C. Oxidation of this double bond with m -CPBA afforded dihydroclerodin.",10.1021/jo991151r,1999-11-20,0.5836251666630476
Organic Letters,Efficient Synthesis of 5<i>H</i>-Cyclopenta[<i>c</i>]quinoline Derivatives via Palladium-Catalyzed Domino Reactions of <i>o</i>-Alkynylhalobenzene with Amine,"A novel and efficient route for the synthesis of 5H-cyclopenta[c]quinoline derivatives via a palladium-catalyzed domino reaction of o-alkynylhalobenzene with amine is described. The starting materials are easily available, and the reaction proceeds smoothly with high efficiency, which shows broad scope with good functional group tolerance.",10.1021/ol103173v,2011-02-09,0.5836247908758655
Journal of Organic Chemistry,"A Unified Strategy toward the Synthesis of Acerogenin-Type Macrocycles:  Total Syntheses of Acerogenins A, B, C, and L and Aceroside IV","A general strategy for the synthesis of acerogenin-type diarylheptanoids containing an endocyclic biaryl ether bond has been developed, and convergent total syntheses of acerogenin A, B, C, and L and aceroside IV have been accomplished. Cycloetherification of the linear diarylheptanoid 1-(4-fluoro-3-nitrophenyl)-7-(3-hydroxy-4-methoxyphenyl)heptan-3-one (18) under mild conditions (CsF, DMF, 0.01 M, rt, 5 h) gave the macrocycle 4-methoxy-17-nitro-2-oxatricyclo[13.2.2(3,7)]eicosa-1(18),3,5,7(20),15(19),16-hexaen-12-one (19) in 95% yield. Removal of the nitro group followed by O-demethylation gave acerogenin C (2), whose reduction afforded acerogenin A (1). Glucosidation of 2 with 2,3,4,6-alpha-D-tetrabenzoylglucopyranosyl bromide followed by saponification gave aceroside IV (3) in excellent overall yield. Acerogenins B (4) and L (5) were synthesized in a similar fashion featuring a key intramolecular S(N)Ar reaction of linear compound 29. The entropy driving force resulting from the preorganization of cyclization precursors in favor of the bent conformation was proposed to contribute significantly to the efficiency of this cyclization. Both computational studies and spectroscopic data (NOE) supported this hypothesis. Experimentally, it was observed that even at high concentration (1 M of 18 in DMF) the analytically pure macrocycle 19 could still be obtained in 45-50% isolated yield. Furthermore, when the cyclization of 18 was carried out in the presence of an external nucleophile (4-methoxyphenol, 33) or an electrophile (4-fluoro-3-nitrotoluene, 34), only the 15-membered cyclophane 19 was isolable. This provides experimental evidence that compound 18 is indeed preorganized in such a way that intramolecular reaction was highly competitive with the alternative intermolecular process.",10.1021/jo981844s,1999-01-20,0.5836237404130165
European Journal of Organic Chemistry,An Efficient Route to Pentasubstituted Phenols,"Abstract A simple and convenient three‐step protocol for the synthesis of pentasubstituted tribromophenols based on the acid‐catalyzed Grob‐type fragmentation of the bicyclic ketone precursors 8a – e in high overall yield is described. The bicyclic ketones 8a – e were obtained in two steps starting from the Diels–Alder cycloadducts 5a – e of β‐substituted vinyl acetates and tetrabromo‐5,5‐dimethoxycyclopentadiene. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2006)",10.1002/ejoc.200500603,2005-11-30,0.5836207016858429
Tetrahedron,An expedient and selective route to crowned morphine and isomorphine congeners. A probe for ionophore and molecular recognition of opiate receptor,,10.1016/s0040-4039(01)81378-2,1984-01-01,0.5836201770395943
Tetrahedron,"Synthesis and resolution of a new chiral C2-symmetric bisphenol: trans-1,2-bis(2-hydroxyphenyl)cyclopentane",,10.1016/s0040-4039(97)00421-8,1997-04-01,0.5836185823416807
Tetrahedron,Synthetic study of tautomycetin: Synthesis of two large subunits,,10.1016/s0040-4039(97)10100-9,1997-11-01,0.5836146523698595
Chemical Science,Total synthesis of atropisomeric indolosesquiterpenoids <i>via</i> N–N bond formation: dixiamycins A and B,The total synthesis of the naturally occurring N–N atropo-diastereomers dixiamycin A (1a) and dixiamycin B (1b) using a key Cu( i )-catalyzed aerobic oxidation of xiamycin A methyl ester (2b) was developed.,10.1039/d2sc07119c,2023-01-01,0.583605570774596
Tetrahedron,Oxidative cyclotrimerization of unsaturated compounds with DDQ and triflic acid: An efficient synthetic route to triply-fused benzene rings,,10.1016/j.tetlet.2014.12.141,2015-01-06,0.5836055493167457
Organic Letters,Matteson Homologation-Based Total Synthesis of Lagunamide A,"Matteson homologation was found to be an excellent tool for the synthesis of the polyketide fragment of lagunamide A. Starting from a chiral boronic ester, a central building block containing all stereogenic centers of the polyketide chain was synthesized via six iterative Matteson homologation steps.",10.1021/acs.orglett.8b00576,2018-03-26,0.5836011108392226
Journal of Organic Chemistry,A palladium-catalyzed route to huperzine A and its analogs and their anticholinesterase activity,"Huperzine A is an alkaloid isolated from Huperzia serrata (Thunb.) Trev., a Chinese club moss the extracts of which have been used in Chinese folklore medicine to treat a variety of maladies including memory disorders. Recently, this molecule has attracted widespread attention because of its possible use in the treatment of Alzheimer's disease (AD). We describe herein a palladium-catalyzed bicycloannulation route to this molecule which makes huperzine A available in 40% overall yield. The application of this methodology to seven other huperzine A analogues together with their biological activity in the inhibition of rat cortex acetylcholinesterase (AChE) is detailed herein. None of these new compounds was more potent than the parent structure as AChE inhibitors.",10.1021/jo00079a008,1993-12-01,0.5835979279619518
Organic Letters,<i>O</i>-Perhalopyridin-4-yl Hydroxylamines: Amidyl-Radical Generation Scaffolds in Photoinduced Direct Amination of Heterocycles,"Reported herein is the design and synthesis of new O -perhalopyridin-4-yl hydroxylamines as shelf-stable and versatile amidyl-radical precursors. The novel amination reagents can be easily prepared via a single synthetic step from inexpensive commercially available starting materials using monoprotected HONH 2 as amino source. The synthetic potency of the developed reagents was well demonstrated by direct amination of a series of quinoxalin-2(1 H )-ones and their analogues under photocatalytic conditions, even without any additive and photocatalysts.",10.1021/acs.orglett.1c00064,2021-02-15,0.5835978251610747
European Journal of Organic Chemistry,"Isolation and Synthesis ofN-(2-Methyl-3-oxodec-8-enoyl)-2-pyrroline and 2-(Hept-5-enyl)-3-methyl-4-oxo-6,7,8,8a-tetrahydro-4H-pyrrolo[2,1-b]1,3-oxazine – Two New Fungal Metabolites with in vivo Anti-Juvenile-Hormone and Insecticidal Activity","Two new natural products, N-(2-methyl-3-oxodec-8-enoyl)-2-pyrroline (2) and 2-(hept-5-enyl)-3-methyl-4-oxo-6,7,8,8a-tetrahydro-4H-pyrrolo[2,1-b]-1,3-oxazine (3), have been isolated from Penicillium brevicompactum Dierckx. Compound 2 has shown an important in vivo anti-juvenile-hormone (anti-JH) activity while compound 3 has exhibited insecticidal activity against Oncopeltus fasciatus Dallas. Both products have been synthesized starting from 1,4-hexadiene, by means of a sequence of reactions which includes the preparation of 6-octenoic acid and its transformation into the corresponding acid chloride, in order to acylate Meldrum's acid. Subsequent aminolysis with pyrrolidine, followed by methylation at the activated position of the β-oxo amide with iodomethane, introduction of a methoxy group at the pyrrolidine ring by anodic oxidation and final elimination of methanol on SiO2 led to 2 and 3. The fact that both metabolites can be prepared by the same sequence indicates that they must be biogenetically related. Based on structural similarities, compounds 2 and 3 are also closely related to the recently discovered brevioxime (1).",10.1002/(sici)1099-0690(199901)1999:1<221::aid-ejoc221>3.0.co;2-y,1999-01-01,0.5835976982173137
Synthesis,Studies towards the Total Synthesis of Kadcotrione B,"A convergent and efficient approach towards the total synthesis of Kadcotrione B is described. For this purpose, the syntheses of two fragments, 6/6/5-fused tricyclic ring and C-9 side chain, were accomplished. The salient features of these syntheses are the utilization of aldol condensation, Evans aldol reaction, Horner–Wadsworth–Emmons olefination, Michael addition, Robinson annulation, and Wacker oxidation.",10.1055/s-0039-1691494,2019-11-21,0.5835852373410539
Tetrahedron,"A novel procedure for the synthesis of 1′,2′- nucleosides",,10.1016/s0040-4039(00)72819-x,1966-01-01,0.5835823797094164
Tetrahedron,"A novel procedure for the synthesis of 2,3-dihydrofurans",,10.1016/s0040-4039(00)90139-4,1965-01-01,0.5835823797094164
Organic Letters,"Progress toward the Total Synthesis of Callipeltin A (I):  Asymmetric Synthesis of (3<i>S</i>,4<i>R</i>)-3,4-Dimethylglutamine","[reaction:see text] During the total synthesis of the novel cyclic depsipeptide callipeltin A (1), the unit (3S,4R)-3,4-dimethylglutamine, was successfully synthesized by asymmetric Michael addition and subsequent electrophilic azidation. The key feature of this approach is the generation of three adjacent stereogenic centers using the same camphorsultam chiral auxiliary.",10.1021/ol006679t,2000-12-01,0.583581190323868
Organic Letters,A Biomimetic Approach to Lanthionines,"The asymmetric sulfa-Michael additions of appropriately protected L- and D-cysteine derivatives to new chiral dehydroamino acid derivatives have been developed as key steps in the synthesis of biologically important cysteine derivatives, such as lanthionine (Lan) and β-methyllanthionine (MeLan), which are unusual bis-α-amino acids found in the emerging lantibiotics such as nisin.",10.1021/ol203068s,2011-12-16,0.583580471838235
European Journal of Organic Chemistry,"Enantioselective Total Synthesis of 1,3‐Disubstituted β‐Carboline Alkaloids, (–)‐Dichotomine A and (+)‐Dichotomide II","Abstract ( S )‐(–)‐Dichotomine A and its enantiomer were synthesized from the key intermediate, methyl 1‐(1‐hydroxyethyl)‐β‐carboline‐3‐carboxylate, by enantioselective esterification with Lipase QLM. The first total synthesis of (+)‐dichotomide II and its enantiomer were also achieved from ( S )‐(–)‐dichotomine A methyl ester and its enantiomer. The absolute configuration of the stereogenic center of the reported (+)‐dichotomide II was determined to be R .",10.1002/ejoc.201201652,2013-02-06,0.5835754019956156
Synthesis,"A New Convergent Synthesis of 4,4′-Bispyridyl-5,5′-Disubstituted-2,2-Bisoxazoles and -Bisthiazoles","A convergent strategy for the synthesis of 4,4′-bispyridyl-5,5′ -disubstituted-2,2′-bisoxazoles and -bisthiazoles from diamides has been achieved.",10.1055/s-2003-42085,2003-01-01,0.5835744658029033
Synthesis,Synthesis of Helquats Based on Phenanthridinium Units: Four-Step Procedure to Novel Extended Helical Dications,Three novel helical dications (helquats) containing phenanthridinium units have been synthesized from 6-(pyridin-2-ylethyn­yl)phenanthridine as a common precursor prepared by Sonogashira coupling of phenanthridin-6-yl triflate with 2-ethynylpyridine. Bisquaternization of the common precursor followed by rhodium-catalyzed [2+2+2] cycloisomerization led to the title helical dicationic scaffolds. The connectivity and spatial arrangement of the three target helquats were unambiguously established by X-ray crystal structure analysis.,10.1055/s-0034-1381136,2015-08-10,0.5835738876142942
Tetrahedron,A safe and scalable synthesis of 2-hydroxy-3-alkoxypropionates by epoxide ring opening,,10.1016/j.tetlet.2015.06.080,2015-07-04,0.5835736819573869
Tetrahedron,An efficient regio-specific synthetic route to multiply substituted acyl-sulphated β-cyclodextrins,,10.1016/s0040-4039(01)01992-x,2001-12-01,0.5835714900257876
Synlett,Synthesis of a Glycosylated<i>ortho</i>-Carboranyl Amino Acid,"The preparation of an ortho-carborane derivative bearing both carbohydrate and amino acid substituents is presented; opening of a glucofuranuro-γ-lactone derivative with propargylamines, cycloaddition of decaborane to an acetylenic bond and amidation with a N-Fmoc-glutamate derivative are the key-steps in this synthesis.",10.1055/s-2003-40834,2003-01-01,0.5835669733690184
Synthesis,"Chemoenzymatic Access to (+)-Artabotriol and its Application in Collective Synthesis of (+)-Grandiamide D, (–)-Tulipalin B, (+)-Spirathundiol, and (+)-Artabotriolcaffeate","Starting from dimethyl (±)-2-hydroxy-3-methylenesuccinnate chemoenzymatic collective formal/total synthesis of enantiomerically pure bioactive natural products has been described via the advanced level common precursor (+)-artabotriol. An efficient enzymatic resolution with high enantiomeric purity, selective diester to diol reduction, and requisite dehydrative coupling reactions without any racemization are the significant topographies.",10.1055/s-0035-1561588,2016-04-12,0.5835651323013532
Organic Process Research & Development,A High-Throughput Impurity-Free Process for Gatifloxacin,"An improved process to obtain gatifloxacin ( 1 ) through use of boron chelate intermediates has been developed. The methodology involves an initial activation step which accelerates the formation of the first chelate under low-temperature conditions and prevents demethylation of the starting material. To increase the overall yield and to avoid the isolation and manipulation of the resulting intermediates, the process has been designed to be carried out in one pot. As a result, we present here an easy, scaleable and substantially impurity-free process to obtain gatifloxacin ( 1 ) in high yield.",10.1021/op800042a,2008-08-21,0.5835609528479538
European Journal of Organic Chemistry,Asymmetric Syntheses of Potent Antitumor Macrolides Cryptophycin B and Arenastatin A,"Abstract Efficient and highly stereoselective syntheses of cryptophycin B and arenastatin A, potent cytotoxic agents, are described. An ester‐derived titanium enolate mediated syn ‐aldol reaction was employed to generate the stereocenters C‐5 and C‐6. The route is convergent and provides a convenient access to the synthesis of structural variants of cryptophycins as well as members of its family. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2004)",10.1002/ejoc.200300814,2004-04-27,0.5835556172680267
Tetrahedron,Chyhotrypsin-catalyzed fragment coupling synthesis of D-Phe(6)-GnRH,,10.1016/s0040-4039(00)88550-0,1990-01-01,0.5835508949171223
Synthesis,Simple Synthesis of Some 2-Substituted Melatonin Derivatives,A simple strategy for the synthesis of some 2-substituted melatonin derivatives using p-anisidine as starting material is reported. The key step is a chemoselective reduction of a cyano group in the presence of an appropriate acid anhydride by hydrogenation over Adams’ catalyst or with sodium borohydride in the presence of catalytic amounts of anhydrous nickel(II) chloride. The 2-substituted melatonin derivatives were obtained in six or seven steps from inexpensive p-anisidine in 9-13% overall yield.,10.1055/s-0030-1258361,2010-12-14,0.5835489671138406
Tetrahedron,"A convergent and stereoselective total synthesis of (−)-crispine A, (−)-benzo[a]quinolizidine and (−)-salsolidine",,10.1016/j.tetlet.2013.05.132,2013-06-07,0.5835468466338697
Tetrahedron,"A short synthesis of quinazolinocarboline alkaloids rutaecarpine, hortiacine, euxylophoricine A and euxylophoricine D from methyl N-(4-chloro-5H-1,2,3-dithiazol-5-ylidene)anthranilates",,10.1016/s0040-4039(02)00711-6,2002-05-01,0.5835456385126828
Tetrahedron,Chemistry of insect antifeedants from azadirachta indica (part 6): Synthesis of an optically pure acetal intermediate for potential use in the synthesis of azadirachtin and novel antifeedants.,,10.1016/s0040-4039(00)94574-x,1990-01-01,0.583540125837282
Organic Letters,Total Synthesis of Trisaccharide Repeating Unit of <i>Staphylococcus aureus</i> Strain M,"An efficient total synthesis of a conjugation-ready trisaccharide repeating unit of Staphylococcus aureus strain M is reported here. The main challenges involved in this synthesis are the procurement of rare sugars ( d -FucNAc and d -GalNAcA) and installation of consecutive 1,2- cis -glycosidic linkages between them. Stereoselective 1,2- cis glycosylation with the linker acceptor was achieved with easily accessible benzylidene protected d -galactosamine thioglycoside by employing a DMF modulated preactivation glycosylation method. The consecutive 1,2- cis linkages were installed with the help of solvent participation. The carboxylic acid functionality was introduced via postglycosylation oxidation on the disaccharide moiety. The total synthesis of trisaccharide repeating unit was accomplished with the longest linear sequence of 24 steps in 4.5% overall yield.",10.1021/acs.orglett.3c00997,2023-04-13,0.5835382100100509
Tetrahedron,A new synthesis of squalene using 2-alkenylthio-thiazolinelithium derivative,,10.1016/s0040-4039(01)97441-6,1971-01-01,0.5835356847600196
Organic Process Research & Development,"Development of a Practical, Safe, and High-Yielding Process for the Preparation of Enantiomerically Pure <i>trans</i>-Cyclopropane Carboxylic Acid","A practical, safe, and high-yielding process for the cyclopropanation of a chiral epoxide has been developed using the inexpensive and nonhazardous reagents triethylphosphonoacetate and sodium tert -butoxide.",10.1021/op0202033,2002-07-04,0.5835335630436055
Tetrahedron,"Beta-lactams derived from the reaction of phenanthridines and 11H-dibenzo[b,e]azepin-11-one with phenylvaleryl chloride. Synthesis of fused analogs of the cholesterol absorption inhibitor Sch 48461",,10.1016/s0040-4039(98)01648-7,1998-10-01,0.5835213749235844
Journal of Organic Chemistry,Evaluation of Enantiopure <i>N</i>-(Ferrocenylmethyl)azetidin-2-yl(diphenyl)methanol for Catalytic Asymmetric Addition of Organozinc Reagents to Aldehydes,"A facile and practical approach to preparation of enantiopure N-(ferrocenylmethyl)azetidin-2-yl(diphenyl)methanol was developed from cheap and easily available l-(+)-methionine. Synthetic highlights include the three-step, one-pot construction of the chiral azetidine ring and the development of an improved one-step procedure for the synthesis of the key intermediate l-2-amino-4-bromobutanoic acid. Enantiopure N-(ferrocenylmethyl)azetidin-2-yl(diphenyl)methanol was evaluated for catalytic asymmetric addition of organozinc reagents to aldehydes. The asymmetric ethylation, methylation, arylation, and alkynylation of aldehydes achieved enantioselectivity of up to 98.4%, 94.1%, 99.0%, and 84.6% ee, respectively, in the presence of a catalytic amount of chiral N-(ferrocenylmethyl)azetidin-2-yl(diphenyl)methanol. Our results demonstrated further that the four-membered heterocycle-based backbone was a good potential chiral unit for the catalytic asymmetric induction reaction, and the hindrance of the bulky ferrocenyl group, compared to a phenyl group, played an important role in the enantioselectivities. A possible transition for the catalytic asymmetric addition has been proposed on the basis of the crystal structure of the chiral ligand 3b including two HOAc molecules and previous studies.",10.1021/jo701943x,2007-12-07,0.5835176784017164
Synthesis,An Improved Preparation of Vinylogous Thiocarboxamides,,10.1055/s-1979-28879,1979-01-01,0.5835170163400987
Synthesis,Improved Preparation of 1-Deuteriated Benzaldehydes,,10.1055/s-1980-29266,1980-01-01,0.5835170163400987
Synthesis,Improved Preparation of 2-Nitrodiphenylamines,,10.1055/s-1980-28968,1980-01-01,0.5835170163400987
Tetrahedron,Improved preparation of tosyldiazomethane,,10.1016/s0040-4039(00)00763-2,2000-07-01,0.5835170163400987
Tetrahedron,"Exploration of a proposed biomimetic synthetic route to plumarellide. Development of a facile transannular Diels–Alder reaction from a macrocyclic enedione leading to a new 5,6,7-tricyclic ring system",,10.1016/j.tetlet.2010.10.154,2010-11-05,0.5835142483325269
Organic Letters,Enantioselective Synthesis of a Cyclopropane Derivative of Spliceostatin A and Evaluation of Bioactivity,Spliceostatin A is a potent inhibitor of spliceosomes and exhibits excellent anticancer activity against multiple human cancer cell lines. We describe here the design and synthesis of a stable cyclopropane derivative of spliceostatin A. The synthesis involved a cross-metathesis or a Suzuki cross-coupling reaction as the key step. The functionalized epoxy alcohol ring was constructed from commercially available optically active tri- O-acetyl-d-glucal. The biological properties of the cyclopropyl derivative revealed that it is active in human cells and inhibits splicing in vitro comparable to spliceostatin A.,10.1021/acs.orglett.8b03228,2018-11-05,0.5835135830667048
Journal of the American Chemical Society,C−H Bonds as Ubiquitous Functionality: A General Approach to Complex Arylated Pyrazoles via Sequential Regioselective <i>C</i>-Arylation and <i>N</i>-Alkylation Enabled by SEM-Group Transposition,"Pyrazoles are important azole heteroarenes frequently found in pharmaceuticals and protein ligands, and there has been a growing interest in new synthetic methods for their preparation. We report the first catalytic intermolecular C-H arylation of pyrazoles, namely SEM-protected pyrazoles and N-alkylpyrazoles, which lays the foundation for a new approach to the synthesis of complex arylated pyrazoles, where new arene rings are directly attached to predetermined positions of the heteroarene nucleus (""topologically obvious synthesis""). Through a systematic search, we identified a palladium-pivalate catalytic system as the most effective protocol and mapped the reactivity of all three C-H bonds of the pyrazole (C-5 > C-4 >> C-3). To circumvent the low reactivity of the C-3 position, we developed a ""SEM switch"", which transposes the SEM-protecting group from one nitrogen to the other in one step, and in the process transforms the unreactive C-3 position to the reactive C-5 position. The SEM switch thus enables sequential arylation of C-5 and C-3 position, providing rapid access to protected or free 3,4,5-triarylpyrazoles (the C-4 arene ring is readily introduced by bromination and Suzuki coupling). Furthermore, N-alkylation of SEM-protected pyrazoles allows for regioselective introduction of the amine substituent, addressing the low regioselectivity of N-alkylation of pyrazoles lacking sufficient steric bias. Thus, the catalytic C-H arylation combined with the protecting group transposition and N-alkylation provides a rapid route to fully substituted pyrazoles with complete regiocontrol of all substituents. The particular strength of this strategy is the ability to commence the synthesis from either the parent pyrazole or practically any pyrazole intermediate.",10.1021/ja8096114,2009-02-10,0.5835014861771938
Synthesis,"Furan Ring Opening-Pyrrole Ring Closure: A New Route to Pyrrolo[1,2-d][1,4]benzodiazepin-6-ones","A new method for the synthesis of pyrrolo[1,2-d][1,4]benzodiazepines is described. The method is based on the acid-catalyzed recyclization of N-[2-(5-alkyl-2-furyl)phenyl]-2-aminoacetamides and permits the formation of both diazepine and pyrrole rings in one pot. The reaction proceeds via furan ring opening to give the diketone moiety followed by consecutive reactions of the free amino group with both carbonyl functions.",10.1055/s-0030-1260204,2011-09-02,0.5835005984446653
Synlett,Synthetic Approaches to Rapamycin. 2. A Synthesis of a C21-C42 Fragment,"All articles of this category Key steps in a synthesis of a C21-C42 fragment of rapamycin include a [3,3]-sigmatropic rearrangement to introduce the correct relative stereochemistry at C27 and C28 and the use of a furylsilane as a latent hydroxyl group at C28. rapamycin - Fleming-Tamao oxidation - furan photooxidation - silylstannylation - Ireland-Claisen rearrangement",10.1055/s-1996-5603,1996-09-01,0.5834967049917319
Tetrahedron,"A highly efficient chemo- , regio- , and stereoselective synthesis of (7, 9)-dodecadien-1-yl acetate, a sex pheromone of , via a functionalized organoborate",,10.1016/s0040-4039(01)92652-8,1977-01-01,0.5834951615250795
Tetrahedron,Highly efficient Pd-catalyzed synthesis of nitriles from aldoximes,,10.1016/j.tetlet.2009.01.150,2009-02-10,0.583490216470297
Synthesis,"Synthesis of Novel 1,2,3,4-Tetrahydroisoquinoline-3-carboxylic Acid Derivatives through the Application of Rongalite: A Synergistic Combination of [2+2+2]- and [4+2]-Cycloaddition Reactions","An efficient route for the synthesis of several novel 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic) derivatives has been reported. A synergistic combination of [2+2+2]- and [4+2]-cycloaddition reactions has been used for the synthesis of the desired targets.",10.1055/s-2007-965946,2007-03-27,0.5834863178218466
Tetrahedron,"A stereoselective route to 1-chloro-1-halo-enynes, versatile precursors for the synthesis of chloroenediynes and enetriynes",,10.1016/0040-4039(95)00612-g,1995-05-01,0.5834838325041051
Chemical Science,"Organocatalytic atroposelective synthesis of axially chiral <i>N</i> , <i>N</i> ′-pyrrolylindoles <i>via de novo</i> indole formation","The first organocatalytic atroposelective synthesis of chiral N,N ′-pyrrolylindoles based on CPA-catalyzed asymmetric 5- endo-dig cyclization of well-designed o -alkynylanilines bearing pyrrolyl unit was established via de novo indole formation.",10.1039/d3sc03686c,2023-01-01,0.5834791040236207
European Journal of Organic Chemistry,"Gold‐Catalyzed Regioselective Synthesis of Pyrazolo[1,4]oxazepines via Intramolecular <i>7</i>‐<i>endo‐dig</i> Cyclization","An efficient gold‐catalyzed intramolecular regioselective synthesis of pyrazolo[1,4]oxazepines were developed from alkynyl‐substituted pyrazoles via 7‐endo dig cyclization. In this reaction a new C–N bond was formed and substituted pyrazolo[1,4]oxazepines were obtained in moderate to very good yields. Whereas alkynyl‐substituted pyrazoles treated with sodium hydride produced the corresponding pyrazolo[1,4]oxazines regioselectively, via 6‐exo dig cyclization in one‐pot synthesis.",10.1002/ejoc.201901852,2020-05-19,0.5834765961268114
Tetrahedron,"Synthesis of 6,7,8,9-tetrahydropyrido[2,3- b ]indolizine and 3,4-dihydro-2 H -pyrido[2′,3′:4,5]pyrrolo[2,1- b ][1,3]oxazine derivatives as new melatonin receptor ligands",,10.1016/s0040-4039(01)02359-0,2002-02-01,0.583474002243583
Organic Letters,"Facile Synthesis of 1,2,3,4-Tetrahydro-β-carbolines by One-Pot Domino Three-Component Indole Formation and Nucleophilic Cyclization","Two direct synthetic methods of 1,2,3,4-tetrahydro-β-carboline derivatives have been developed. After initial indole formation by copper-catalyzed domino three-component coupling−cyclization using an appropriate ethynylaniline, aldehyde, and a secondary amine, treatment with t -BuOK/hexane or MsOH afforded the desired tetrahydro-β-carboline derivatives in moderate to good yields.",10.1021/ol900460m,2009-04-08,0.5834705358603895
Synthesis,"3-Oxo-1,3λ6,4-oxathiazines: A Novel Class of Heterocyclic S,O-Acetals","In this study, two synthetic methods for the synthesis of a hitherto unknown class of heterocyclic diastereo- and enantiopure S , O -acetals are described. Method A involves a chemoselective monohalogenation of sulfoximines and method B a stereoselective ring opening of sulfonimidates with a carbenoid as the key step, both followed by a base-induced cyclization of the S -(halomethyl)sulfoximine intermediates. The absolute configuration of the resulting 3-oxo-1,3λ 6 ,4-oxathiazines has been confirmed by X-ray structural analysis. Furthermore, the first experiments exploring the reactivity of the new compounds are described.",10.1055/s-0036-1588679,2016-12-08,0.5834678859161503
Organic Process Research & Development,Enantioselective and Step-Economic Synthesis of the Chiral Amine Fragment in the Tyrosine Kinase Inhibitor Repotrectinib by Direct Asymmetric Reductive Amination under Batch and Flow,"A one-step and highly enantioselective synthesis of ( R )-2-(1-aminoethyl)-4-fluorophenol (( R )- I ), a key chiral intermediate toward preparation of the tyrosine kinase inhibitor repotrectinib, has been developed. Starting from the easily available substrate 1-(5-fluoro-2-hydroxyphenyl)ethan-1-one ( 2a ), the target product ( R )- I was prepared in an optically pure form through a Ru-catalyzed asymmetric reductive amination with NH 4 OAc as the nitrogen source and H 2 as the reducing agent. The reaction can be carried out on a 20 g scale using a continuous-flow reactor instead of a traditional batch reactor. The flow technology enables higher reaction efficiency and does not require column chromatography for product purification. Compared to the known procedures, this method avoids the use of expensive chiral auxiliaries and protecting group operations, making it a step-economical and cost-effective alternative strategy for production of repotrectinib.",10.1021/acs.oprd.3c00152,2023-07-07,0.5834671962066565
Tetrahedron,"Keramadine, a novel antagonist of serotonergic receptors isolated from the okinawan sea sponge sp.",,10.1016/s0040-4039(01)81208-9,1984-01-01,0.5834621791807526
Angewandte Chemie International Edition,Synthetic Study of (−)‐Norzoanthamine: Construction of the ABC Ring Moiety,"Throw your hat in the ring: A highly diastereoselective synthesis of the ABC rings of (-)-norzoanthamine has been achieved starting from the (-)-Hajos-Parrish ketone (see scheme). Three asymmetric quaternary carbon centers on the C ring were constructed by a 1,4-addition, and an intramolecular Diels-Alder reaction provided a trans-decalin scaffold on the AB rings.",10.1002/anie.200804544,2008-11-26,0.5834619074643391
Synlett,Gram-Scale Total Synthesis of Cordiachrome B,"Abstract Cordiachromes A–C are terpenoid benzoquinones that exhibit significant antimalarial, antimycobacterial, antifungal, antileishmanial, and cytotoxic activities. Herein, we report a gram-scale total synthesis of cordiachrome B from inexpensive, commercially available 3-methoxybenzaldehyde in six linear steps. Highlights of the synthesis include a Ti(O-i-Pr)4-promoted photoenolization/Diels–Alder (PEDA) reaction to construct the desired cis configuration at the B–C ring junction, matching that of the natural product; an N,N,N′-trimethylethylenediamine-directed regioselective methylation; a Pd-catalyzed ortho-C–H methoxylation enabled by a monodentate transient directing group to give 3,6-dimethoxy-2-methylbenzaldehyde on a large scale for the PEDA reaction; and a Tebbe olefination to convert the carbonyl group into the methylene group required for the natural product. The concise and scalable synthesis provides a novel strategy for producing these natural products and related congeners for further medicinal-chemistry studies. Cordiachrome B was shown, for the first time, to exhibit a moderate antibacterial activity against Staphylococcus aureus and its methicillin-resistant strain.",10.1055/s-0043-1775434,2025-02-10,0.5834558621069176
Synlett,A Stereoselective Approachto the Core Structure of the Polyoxin and Nikkomycin Antibiotics,"A stereoselective synthesis of the core structure of the polyoxin and nikkomycin antibiotics is described. Notable elements of the synthesis include the use of an IBX-based oxidation protocol in the high-yielding production of ribosyl aldehydes, and the use of a diastereoselective zinc-mediated acetylide addition for the generation of the C-5 stereocenter. The synthesis only requires three chromatographic purifications and should be amenable to the large-scale preparation of numerous polyoxin analogs.",10.1055/s-2003-40341,2003-06-30,0.5834535356920685
Organic Process Research & Development,"Development of a Multi Kilogram-Scale, Tandem Cyclopropanation Ring-Expansion Reaction en Route to Hedgehog Antagonist IPI-926","The formation of the d -homocyclopamine ring system in IPI-926 is the key step in its semisynthesis and proceeds via a chemoselective cyclopropanation followed by a stereoselective acid-catalyzed carbocation rearrangement. In order to perform large-scale cyclopropanation reactions, we developed new iodomethylzinc bis(aryl)phosphate reagents that were found to be both effective and safe. These soluble reagents can be prepared under mild conditions and are stable during the course of the reaction. Importantly, they have favorable energetics relative to other cyclopropanating agents such as EtZnCH 2 I. Herein, we describe the process optimization studies that led to successful large-scale production of the d -homocyclopamine core necessary for IPI-926.",10.1021/acs.oprd.6b00048,2016-03-29,0.5834525796181117
Organic Letters,Beyond the Roche Ester: A New Approach to Polypropionate Stereotriad Synthesis,"An efficient, step-economical, and scalable approach to the synthesis of polypropionate stereotriads has been developed. Either 2-butyne or propyne is subjected to rhodium-catalyzed silylformylation and in situ crotylation of the resulting aldehydes. Tamao oxidation under either ""standard"" conditions or ""aprotic"" conditions then delivers the completed stereotriads in a three-step, two-pot sequence. In contrast to the classical Roche ester approach, the α-stereocenter is obtained for ""free.""",10.1021/ol500051e,2014-02-06,0.5834479117999444
Journal of Organic Chemistry,Synthesis of <scp>d</scp>-<i>erythro</i>-Sphinganine through Serine-Derived α-Amino Epoxides,"A total synthesis of D-erythro-sphinganine [(2S,3R)-2-aminooctadecane-1,3-diol] starting from commercial N-tert-butyloxycarbonyl-L-serine methyl ester is described. The approach is based on the completely stereoselective preparation of an α-amino epoxide obtained by treating a protected L-serinal derivative with dimethylsulfoxonium methylide. The oxirane synthon is obtained with an anti configuration fitting the (2S,3R) stereochemistry of the 2-amino-1,3-diol polar head of D-erythro-sphinganine. The synthetic procedure afforded the target compound in a 68% overall yield based on the initial amount of the starting L-serine material.",10.1021/jo500493c,2014-05-07,0.5834461513436823
Synlett,Stereoselective Total Synthesisof (+)-Valienamine and (+)-4-<i>epi</i>-Valienamine viaa Ring-Closing Enyne Metathesis Protocol,"Stereoselective total synthesis of (+)-valienamine is reported utilizing Sharpless asymmetric dihydroxylation, diastereoselective Carreira alkynylation, and ring-closing enyne metathesis (RCEYM) as key steps from l-serine. A similar strategy is also reported for the first total synthesis of (+)-4-epi-valienamine.",10.1055/s-0028-1087669,2009-01-15,0.5834436293940514
Organic Letters,Potent Glucosidase Inhibitors: De-<i>O</i>-sulfonated Ponkoranol and Its Stereoisomer,"Ponkoranol, a glucosidase inhibitor isolated from the plant Salacia reticulata, comprises a sulfonium ion with an internal sulfate counterion. An efficient synthetic route to de-O-sulfonated ponkoranol and its 5'-stereoisomer is reported, and it is shown that these compounds are potent glucosidase inhibitors that inhibit a key intestinal human glucosidase, the N-terminal catalytic domain of maltase glucoamylase, with K(i) values of 43 +/- 3 and 15 +/- 1 nM, respectively.",10.1021/ol1004005,2010-03-10,0.5834416036547492
Synthesis,Synthesis of (±)-5-epi-Vetiverianine A via an Oxidative Cyclization Approach,"Abstract In this article, we report the synthesis of (±)-5-epi-vetiverianine A. The key reactions, including a rhodium-catalyzed coupling reaction and an oxidative phenolic cyclization, allow for efficient and stereoselective access to (±)-5-epi-vetiverianine A in 11 steps, and in 20% overall yield. The stereochemistry is confirmed by NOE studies.",10.1055/a-1947-6049,2022-09-20,0.5834405393086436
Journal of the American Chemical Society,"Total Synthesis of Celastrol, Development of a Platform to Access Celastroid Natural Products","Celastroid natural products, triterpenes, have been and continue to be investigated in clinical trials. Celastrol, and for that matter any member of the celastroid family, was prepared for the first time through chemical synthesis starting from 2,3-dimethylbutadiene. A triene cyclization precursor generated in 12 steps underwent a nonbiomimetic polyene cyclization mediated by ferric chloride to generate the generic celastroid pentacyclic core. In the cyclization, engagement of a tetrasubstituted olefin formed adjacent all carbon quaternary centers stereospecifically. With access to the carbocyclic core of the family of natural products, wilforic acid and wilforol A were prepared en route to racemic celastrol.",10.1021/jacs.5b06261,2015-09-02,0.5834382182238739
Tetrahedron,Synthesis of new bis-calix[4]arenes with imine linkages. A search for new silver-selective sensors,,10.1016/s0040-4039(01)00970-4,2001-07-01,0.5834371308926715
Tetrahedron,"Synthesis of lysophosphatidylserine with 19:4 acyl group, as a novel sodium-potassium atpase inhibitor, in relation to dlis-2, an endogenous digoxin-like substance",,10.1016/s0040-4039(00)94492-7,1990-01-01,0.5834369222712373
Organic Letters,"Anionic Indole <i>N</i>-Carbamoyl N → C Translocation. A Directed remote Metalation Route to 2-Aryl- and 2-Heteroarylindoles. Synthesis of Benz[<i>a</i>]carbazoles and Indeno[1,2-<i>b</i>]indoles","A new LDA-induced anionic N-C carbamoyl migration of 2-arylindoles (7) is reported. Treatment of N-carbamoylindoles 10 and 13, readily available by direct and ipso-borodesilylative Suzuki-Miyaura cross-coupling routes from 8 and 12, respectively, provides a general route to functionalized 2-arylindoles 11 and 14, respectively (Tables 1 and 2). The reaction has been applied to the synthesis of benzo[ a]carbazoles 16 and indeno[1,2- b]indoles 18, and its intramolecularity has been established by a crossover experiment (Scheme 4).",10.1021/ol800307g,2008-06-11,0.5834365598720075
Journal of Organic Chemistry,"Selective C-Acylation of 2-Aminoimidazo[1,2-<i>a</i>]pyridine: Application to the Synthesis of Imidazopyridine-Fused [1,3]Diazepinones","A series of 20 optically pure 3,4-dihydro-5H-pyrido[1',2':1,2]imidazo[4,5-d][1,3]diazepin-5-ones which form a new family of azaheterocycle-fused [1,3]diazepines were synthesized in four steps with 17-66% overall yields. The key step consists of a selective C-acylation reaction of easily accessible 2-aminoimidazo[1,2-a]pyridine at C-3.",10.1021/jo300364d,2012-03-16,0.5834341992740895
Journal of Organic Chemistry,"Reactions of <i>o</i>-Quinone Methides with Pyridinium Methylides: A Diastereoselective Synthesis of 1,2-Dihydronaphtho[2,1-<i>b</i>]furans and 2,3-Dihydrobenzofurans","A simple, general route to the 1,2-dihydronaphtho[2,1-b]furans and 2,3-dihydrobenzofurans substituted at C-2 by an acyl or aryl group, starting from phenolic Mannich bases and pyridinium ylides, has been developed. The mechanism of the reaction is believed to involve the formation of the o-quinone methide intermediate, Michael-type addition of the ylide to the o-quinone methide, followed by intramolecular nucleophilic substitution.",10.1021/jo400621r,2013-05-13,0.5834240183328783
Journal of Organic Chemistry,"Total Synthesis of Optically Active Lycopladine A by Utilizing Diastereoselective Protection of Carbonyl Group in a 1,3-Cyclohexanedione Derivative","We successfully synthesized two enantiomers of bicyclic enones, (7R,7aR)- and (7S,7aS)-9, from the hemiacetal 2a, which we first synthesized from the symmetrical diketone 1a via diastereoselective carbon-oxygen bond formation between one of the carbonyl groups and the chiral alcohol on the C2 side chain in a 2,2-disubstituted 1,3-cycloalkanedione derivative. We also report the total synthesis of natural (+)-lycopladine A [(+)-6] from (7R,7aR)-9 and the formal synthesis of unnatural (-)-lycopladine A [(-)-6] from (7S,7aS)-9.",10.1021/jo200418y,2011-05-04,0.5834221167707941
Organic Letters,Synthesis of the Cytotrienin A Core <i>via</i> Metal Catalyzed C−C Coupling,"A synthetic approach to the C17-benzene ansamycins via metal catalyzed C-C coupling is described. Key bond formations include direct iridium catalyzed carbonyl crotylation from the alcohol oxidation level followed by chelation-controlled Sakurai-Seyferth dienylation to form the stereotriad, which is attached to the arene via Suzuki cross-coupling. The diene-containing carboxylic acid is prepared using rhodium catalyzed acetylene-aldehyde reductive C-C coupling mediated by gaseous hydrogen. Finally, ring-closing metathesis delivers the cytotrienin core.",10.1021/ol200160p,2011-02-16,0.5834215581575193
Journal of Organic Chemistry,Convergent Syntheses of Isomeric Imidazolospiroketones as Templates for Acetyl-CoA Carboxylase (ACC) Inhibitors,"The synthesis of imidazole fused spirocyclic ketones as templates for acetyl-CoA carboxylase (ACC) inhibitors is reported. By completing the spirocyclic ring closure via divergent pathways, the synthesis of these regioisomers from common intermediates was developed. Through an aldehyde homologation/transmetalation strategy, one isomer was formed selectively. The second desired isomer was obtained via an intramolecular aromatic homolytic substitution reaction. Preparation of these isomeric spiroketones provided templates which, upon elaboration, led to key structure-activity relationship (SAR) points for delivery of potent ACC inhibitors.",10.1021/acs.joc.3c01374,2023-09-26,0.5834208517479795
Green Chemistry,Selective palladium-catalysed synthesis of diesters: alkoxycarbonylation of a CO <sub>2</sub> -butadiene derived δ-lactone,"A selective domino reaction has been developed for the valorization of a well-known δ-lactone synthesized by the telomerization of 1,3-butadiene and CO <sub>2</sub> .",10.1039/c7gc01366c,2017-01-01,0.5834202053443199
Organic Letters,Total Synthesis of (±)-Gracilioether F,"Total synthesis of (±)-gracilioether F was achieved via a pivotal reductive cleavage of 1,2-dioxane from allenic ester in 11 steps. The key 1,2-dioxane species, derived from singlet oxygen and a diene, could be used as a common precursor for a stereocontrolled formation of the crucial 1,4-diol through a reductive cleavage.",10.1021/acs.orglett.6b00161,2016-02-16,0.5834195284707508
Journal of Organic Chemistry,"1,4-Disubstituted and 1,4,5-Trisubstituted 2-[(Benzotriazol-1-yl)methyl]pyrroles as Versatile Synthetic Intermediates","The CH(2)Bt substituent, unlike previously used CH(2)X substituents, enables (i) the synthetic elaboration of pyrroles with unsubstituted ring positions and (ii) electrophilic as well as nucleophilic substitutions to give pyrroles of type pyrrolyl-2-CHENu. Thus, 1,4-disubstituted (7) and 1,4,5-trisubstituted 2-[(benzotriazol-1-yl)methyl]pyrroles (15) were easily prepared from the reaction of 5-(benzotriazol-1-yl)-1,2-epoxy-3-pentynes 4 or 14 with primary amines in i-PrOH. The 2-(benzotriazol-1-yl)methyl side chains of compounds 7 and 15 were elaborated by nucleophilic substitution and also by initial alkylation followed by replacement or elimination of the benzotriazolyl moiety to afford a variety of 1,2,4-trisubstituted (6, 8-9, 11-13) and 1,2,4,5-tetrasubstituted pyrroles (18, 20-22).",10.1021/jo951894m,1996-01-01,0.5834163016507425
Tetrahedron,A novel chiral synthetic equivalent of glyoxal and its application to the asymmetric synthesis of O-protected α-hydroxy aldehydes,,10.1016/s0040-4039(99)00095-7,1999-03-01,0.5834130899243769
Organic Letters,"Easy and Stereoselective Approach to α,β-Unsaturated γ-Lactones Fused to Pyranoses from Furanose Scaffolds","The first facile and efficient route to pyranose-fused butenolides from furanose scaffolds, convenient for scaling up production, is described. Wittig olefination of 1,2-O-isopropylidene pentofuranos- or hexofuranos-3-uloses with a resonance-stabilized ylide led to the stereoselective formation of the (Z)-alpha,beta-unsaturated ester. In the presence of acid labile 5-O- or 5,6-di-O-protecting groups, acid hydrolysis of the Wittig product resulted in isomerization to the pyranose form and spontaneous lactonization to give the target molecules in good overall yield.",10.1021/ol071351m,2007-07-26,0.5834122204214441
Journal of Organic Chemistry,Total Synthesis of Hygrolines and Pseudohygrolines,"A concise two-step synthesis of all four diastereoisomeric hygrolines ((-)-hygroline (1), (+)-hygroline (2), (-)-pseudohygroline (3), (+)-pseudohygroline (4)) has been developed based on the (-)-sparteine (5)- or (+)-sparteine surrogate 11-mediated enantioselective lithiation of N-Boc pyrrolidine (6), followed by reaction of the chiral anion with (S)- or (R)-propylene oxide. Reduction of the resulting N-Boc amino alcohols furnished hygrolines and pseudohygrolines in 30% to 56% overall yields with dr's > 95:5.",10.1021/jo4017343,2013-10-08,0.5834054745908557
Journal of Organic Chemistry,Reversal of Reactivity of Heyns Intermediate for the Concise Synthesis of Substituted 3-Hydroxyquinolines,"An efficient and general method for the synthesis of 3-hydroxyquinolines has been achieved from o -acylanilines and α-hydroxyketones in good yields. The strategy involves the intramolecular reverse trapping of the in situ generated aminoenol intermediate with an electrophilic carbonyl, viz . an interrupted Heyns rearrangement, followed by aromatization. Important features include good functional group tolerance, operational simplicity, gram-scale synthesis, and broad synthetic utility.",10.1021/acs.joc.4c01285,2024-11-04,0.5834040362048063
Synthesis,Stereoselective Synthesis of Tetrahydrofuran Lignans,"This short review aims to summarize the reports on stereoselective synthesis of naturally occurring tetrahydrofuran lignans published during the period of 2006 to 2018. The stereoselective construction of non-natural tetrahydrofuran frameworks is not included in this review. 1 Introduction 2 Stereoselective Synthesis of 2,5-Diaryltetrahydrofuran (CL5-a) 2.1 Synthesis of CL5-a via Friedel–Crafts Arylation or Nucleophilic Addition/Reduction of γ-Butyrolactones 2.2 Synthesis of CL5-a via Intramolecular Cyclization of 1,4-Diaryl­butanediols 2.3 Synthesis of CL5-a via Diastereoselective Hydrogenation of Furan Derivatives 2.4 Synthesis of CL5-a via Cycloaddition Reaction of Substituted Cyclopropane­ Derivatives 3 Stereoselective Synthesis of 2-Aryl-4-benzyltetrahydrofuran (CL5-b) 4 Stereoselective Synthesis of 3,4-Dibenzyltetrahydrofuran (CL5-c) 5 Conclusions",10.1055/s-0037-1610289,2018-10-02,0.5834002944517767
Organic Process Research & Development,Development of a Safe and Scalable Process for the Production of a High-Purity Thiocarbamate-Based Ionizable Lipid as an Excipient in mRNA-Encapsulating Lipid Nanoparticles,"Thiocarbamate lipid 2 was prepared on a 25–50 g scale by coupling a carbamoyl chloride with 3-(dimethylamino)-1-propanethiol. Chromatography, activated charcoal treatment, and washing were required to obtain 2 (57%, light yellow oil) in >98% purity. Lipid 2 was successfully prepared on a 1 kg scale by replacing the carbamoyl chloride with an acyl imidazolium intermediate and coupling with the lipophilic amine salt 8 to give 2 in a higher yield (68%) and greater purity (99.8%, colorless oil) using an improved, chromatography-free, purification protocol. In addition, mutagenic impurities in 2 could be controlled well below required specifications.",10.1021/acs.oprd.1c00076,2021-05-19,0.5833950936362274
Organic Letters,Synthesis of (±)-Angustatin A: Assembly of the Phenanthrene Moiety Despite Increasing Ring Strain,"The synthesis of (±)-angustatin A, a phenanthrene-containing cyclophane that possesses conformational chirality, is reported. Key steps include a Pd-catalyzed Negishi coupling to assemble the necessary terphenyl intermediate, its closure into a 14-membered macrocycle via a catalytic-in-phosphine Wittig olefination, and finally a Pt-catalyzed alkyne hydroarylation, which is able to assemble the phenanthrene unit despite the thermodynamic cost of significantly bending arene A from the ideal plane.",10.1021/acs.orglett.3c02742,2023-09-25,0.5833901765956014
Tetrahedron,"Synthesis of carlosic acid, viridicatic acid and carlic acid methyl ester",,10.1016/s0040-4039(01)91752-6,1974-01-01,0.5833882162055026
Organic Letters,Synthesis of a Biomimetic Tetracyclic Precursor of Aspochalasins and Formal Synthesis of Trichoderone A,"Aspochalasins are leucine-derived cytochalasins. Their complexity is associated with a high degree of biosynthetic oxidation, herein inspiring a two-phase strategy in total synthesis. We thus describe the synthesis of a putative biomimetic tetracyclic intermediate. The constructive steps are an intramolecular Diels-Alder reaction to install the isoindolone core of cytochalasins, whose branched precursor was obtained from a stereoselective Ireland-Claisen rearrangement performed from a highly unsaturated substrate. This also constitutes a formal synthesis of trichoderone A.",10.1021/acs.orglett.1c01922,2021-07-22,0.5833876071701257
Journal of the American Chemical Society,Total Synthesis of (+)-Xestoquinone Using an Asymmetric Palladium-Catalyzed Polyene Cyclization,"The first total asymmetric synthesis of (+)-xestoquinone ( 1 ) has been accomplished in 68% ee by a palladium(0)-catalyzed polyene cyclization of naphthyl triflate 44 using ( S )-(+)-BINAP as the chiral ligand. Attempts at an asymmetric polyene cyclization using the corresponding naphthyl bromide 41 gave poor enantioselectivities even in the presence of silver salts, thus exemplifying the effect of the coordination state of palladium on the enantioselectivity. A new method for the preparation of 6,7-dihydroisobenzofurans is also described using a [1,2]-Wittig rearrangement on a seven-membered cyclic ether precursor.",10.1021/ja960807k,1996-01-01,0.583382366856697
Tetrahedron,A new efficient method in nucleoside synthesis,,10.1016/0040-4039(96)01929-6,1996-11-01,0.583381792510732
Synthesis,"(<i>Z</i>)-3-Alkylidene-4,5-dihydro-4-hydroxy-5-methyl-2-(3<i>H</i>)-furanones by Regio- and Diastereo-selective Ene Reaction of Singlet Oxygen (Schenk Reaktion) with γ-Hydroxy Vinylstannanes: An Enantioselective Synthesis of Dihydromahubanolide B","All articles of this category ( Z )-3-Alkylidene-4,5-dihydro-4-hydroxy-5-methyl-2-(3 H )-furanones 5 were prepared from appropriately substituted propargylic alcohols 1 by a sequence of hydromagnesation to γ-hydroxy vinylstannanes 2 , subsequent photooxygenation and reduction to stannyl diols 3 , iododestannylation to iodo diols 4 , and finally cyclization by palladium-catalyzed carbonylation (for 5a ) or Ni(CO) 2 (PPh 3 ) 2 (for 5b,c ). The reaction sequence can be performed enantioselectively by starting with chiral propargylic alcohols. The current approach constitutes a convenient four-step synthesis of optically active lactones 5 from readily available starting materials and is applied herein to the preparation of the natural lactone dihydromahubanolide B.",10.1055/s-1994-25525,1994-01-01,0.5833799524867456
Tetrahedron,"Efficient synthesis of novel pentacyclic 6,7-dihydro-5a,7a,13,14-tetraaza-pentaphene-5,8-diones",,10.1016/j.tetlet.2005.03.133,2005-04-07,0.5833750290326697
Synlett,Synthesis of ‘Spacer'-Naproxen [2-(6-Methoxybiphenylen-2-yl)propanoic Acid] and -Isonaproxen [2-(7-Methoxybiphenylen-2-yl)propanoic Acid],"The CpCo(CO)2-catalyzed cocyclization of 1,2-diethynyl- 4-methoxybenzene with alkynes can be applied to the synthesis of ‘spacer’-naproxen [2-(6-methoxybiphenylen-2-yl)propanoic acid] and its 7-methoxy isomer, ‘spacer’-isonaproxen. While unsymmetrical alkynes are incorporated without regioselectivity, the methoxy group in 6-methoxy-2,3-bis(trimethylsilyl)biphenylene directs electrophiles to C-3, thus allowing for regiochemical differentiation between the 2- and 3-positions.",10.1055/s-0030-1259718,2011-03-08,0.5833720824810134
Organic Letters,Synthesis of a Potent and Selective Inhibitor of p90 Rsk,Immobilization of Pd(OAc) 2 in Ionic Liquid,10.1021/ol060523x,2006-03-09,0.5833671996777935
Organic Letters,Total Synthesis of (−)-Amathaspiramide F,"The stereoselective total synthesis of the marine alkaloid (-)-amathaspiramide F (1) was achieved from the alpha-hydoxy-alpha-ethynylsilane 2. The crucial steps in this synthesis involved not only the enolate Claisen rearrangement of the alpha-acyloxy-alpha-alkenylsilane 6 for the construction of the nitrogen-containing quaternary carbon center, but also the chemoselective formation of the azaspirohemiaminal 12 using heptamethyldisilazane as the methylamine equivalent and the regioselective dibromination of the phenol moiety of 12 using n-Bu(4)NBrCl(2).",10.1021/ol802179e,2008-10-31,0.5833624024174311
Journal of Organic Chemistry,Palladium-Catalyzed Intramolecular Cyclization of Ynamides: Synthesis of 4-Halo-oxazolones,"A mild and efficient methodology involving Pd(PPh3)4-catalyzed intramolecular cyclization of N-alkynyl alkyloxycarbamates with CuCl2 or CuBr2 for the synthesis of 4-halo-oxazolones was developed. This reaction exhibiting good functional tolerance provided a new, efficient, and rapid synthetic process to 4-halo-oxazolones. The resulting 4-halo-oxazolones can serve as great potential precursors for the 3,4,5-trisubstituted oxazolones via a Pd-catalyzed cross-coupling reaction.",10.1021/acs.joc.5b00071,2015-03-10,0.5833607953272687
Synlett,"An Expedient Route to 3-Chlorothioxanthen-9-one-10,10-dioxide and Derivation by Palladium-Catalyzed Coupling","Chemistry has been developed that allows for the synthesis of a series of novel tricyclic thioxanthen-9-one-10,10-dioxides. A regioselective synthesis of the novel core substrate 3-chlorothioxanthen-9-one-10,10-dioxide was achieved in 85% yield over three steps without the need for chromatographic purification. Subsequent microwave-assisted coupling methodology afforded the desired novel 3-substituted tricyclic compounds in good to excellent yield.",10.1055/s-2006-951520,2006-10-25,0.5833474504458473
European Journal of Organic Chemistry,"One‐Pot, Atom and Step Economy (PASE) Assembly of Trifluoromethylated Pyrimidines from CF<sub>3</sub>‐Ynones","A highly efficient synthetic method for the preparation of of 6‐trifluoromethylated pyrimidines was developed. The reaction of CF 3 ‐substituted ynones and nitrogen 1,3‐bis(nucleophile)s was employed for the one‐pot assembly of the pyrimidine core. The cascade route proceeded through an aza‐Michael addition, intramolecular cyclization, and dehydration reaction sequence to give the target heterocycles in excellent yields (up to 97 %). When acetamidine was used as the bis(nucleophile), the unexpected addition of two equivalents of the CF 3 ‐substituted ynone to the acetamidine was observed.",10.1002/ejoc.201700727,2017-06-19,0.583344898016008
Journal of Organic Chemistry,Highly Stereoselective <i>de Novo</i> Synthesis of <scp>l</scp>-Hexoses,"An efficient and general de novo synthetic route to enantiomerically pure L-hexoses has been accomplished starting from the heterocyclic homologating agent 5,6-dihydro-1,4-dithiin-2-yl[(4-methoxybenzyl)oxy]methane and methyl alpha,beta-isopropylidene-L-glycerate. The sugar scaffold was constructed by an acid-catalyzed domino reaction, which enabled selective preparation of either methyl 2,3-dideoxy-alpha-L-threo-hex-2-enopyranosides or 1,6-anhydro-2,3-dideoxy-beta-L-threo-hex-2-enopyranose as key intermediates. The subsequent double bond functionalization by syn or anti dihydroxylation reactions allowed introduction of the remaining stereogenic centers, leading to desired orthogonally protected L-hexopyranosides with a high degree of diastereoselectivity and with very good overall yields. These and previous results (based on the use of the corresponding L-erythro epimers) contribute to make our approach general and place it among the few methods able to synthesize the whole series of the rare L-hexoses.",10.1021/jo100077k,2010-02-25,0.5833442232039272
Tetrahedron,"Asymmetric synthesis of 1-aryl-1,2,3,4-tetrahydroisoquinolines part 1: aDDITION of chiral phenylacetaldehyde acetals to acylimines",,10.1016/0040-4039(95)01716-u,1995-10-01,0.5833418561943845
Tetrahedron,Bromination of a-ring in dehydroabietic acid derivatives. Total synthesis of teideadiol,,10.1016/s0040-4039(01)82261-9,1974-01-01,0.5833413906933965
Journal of Organic Chemistry,Organocatalytic Enantioselective Michael Addition between 3-(3-hydroxy-1<i>H</i>-pyrazol-1-yl)Oxindole and β<i>-</i>Nitrostyrene for the Preparation of Chiral Disubstituted Oxindoles,"A new enantioselective Michael addition between 3-(3-hydroxy-1 H -pyrazol-1-yl)oxindole, a new synthon generated from isatin N, N′ -cyclic azomethine imine 1,3-dipole, and β-nitrostyrene has been disclosed. A series of chiral 3-(3-oxo-2,3-dihydro-1 H -pyrazol-1-yl) disubstituted oxindoles were obtained in excellent results (up to 97% yield, up to 94% ee) with moderate to good diastereoselectivities (up to 4.3:1 dr).",10.1021/acs.joc.9b03337,2020-06-25,0.5833409776463502
Tetrahedron,"An efficient synthesis of penicillanic acid s,s-dioxide in high yield",,10.1016/s0040-4039(00)89275-8,1985-01-01,0.5833362329808135
Tetrahedron,The reaction between N-chloro-N′-phenylamidines and enamines a novel imidazole ring synthesis,,10.1016/s0040-4039(00)93798-5,1976-05-01,0.5833200274878804
Journal of Organic Chemistry,"Synthesis of the Marine Alkaloid Cylindricine C and Serendipitous Synthesis of Its 2,13-Di-<i>epi</i> Stereoisomer","A new approach to the marine alkaloid cylindricine C afforded its previously unreported (±)-2,13-di- epi stereoisomer as the major product along with a minor amount of the racemic parent alkaloid. Key steps included a stereoselective dianion alkylation of a monoester of 1,2-cyclohexanedicarboxylic acid and an annulation based on the tandem conjugate addition of a primary amine to an acetylenic sulfone, followed by intramolecular acylation of the resulting sulfone-stabilized carbanion. The cis -azadecalin moiety thus formed, comprising the cyclohexane A-ring and enaminone B-ring of the products, was further elaborated by the selenenyl chloride-induced cyclofunctionalization of a pendant butenyl substituent with the enaminone moiety, followed by a seleno-Pummerer reaction. Desulfonylation and enaminone reduction afforded the final products. Molecular modeling and X-ray crystallography provided further insight into these processes.",10.1021/acs.joc.3c01467,2023-09-18,0.5833156157356348
European Journal of Organic Chemistry,A New Iron-Mediated Strategy for the Synthesis of α-Lipoic Acid and Analogues,Dithioester 10 was synthesized in 6 steps from tricarbonyl(diene)iron complex 3. Compound 10 is not only a key intermediate for the synthesis of methyl lipoate (13) but could also be of interest for the preparation of various labelled compounds and structural analogues.,10.1002/(sici)1099-0690(199809)1998:9<1949::aid-ejoc1949>3.0.co;2-8,1998-09-01,0.5833078390976313
Organic Letters,Synthesis of Antimicrobial Natural Products Targeting FtsZ: (+)-Totarol and Related Totarane Diterpenes,"An efficient, convergent synthesis of totarol by a diastereoselective epoxide/alkene/arene bicyclization is described. The reported synthesis enables the preparation of related diterpenes totaradiol and totarolone as well as previously unavailable derivatives that exhibit comparable inhibition of the bacterial cell division protein FtsZ.",10.1021/ol100929z,2010-07-02,0.5833056645626526
Tetrahedron,The use of McMurry coupling for the synthesis of indolophanes and cis-stilbenophanes,,10.1016/j.tetlet.2004.06.020,2004-07-07,0.5833026766227862
Journal of Organic Chemistry,Synthesis of Some Unsymmetrical Bridged Terpyridines,"Novel unsymmetrical terpyridines 1 and 2 are synthesized using intra- and intermolecular Michael additions as the key reactions, followed by the construction of the central pyridine ring. Terpyridine 1 represents a heretofore unknown hexacyclic ring system.",10.1021/jo016250v,2002-03-13,0.5833022676846739
Tetrahedron,Total synthesis of the pollen-growth inhibitor (−)-emeniveol. Assignment of absolute stereochemistry,,10.1016/s0040-4039(00)60131-4,1993-11-01,0.583301742684355
Organic Letters,Chemical Ligation-Mediated Total Synthesis of Corramycin,"The ligation-mediated total synthesis of corramycin, a myxobacterial natural product of the strain Corallococcus coralloides, is presented. The synthetic strategy included using two consecutive chemical ligations for a modular and efficient preparation. Finally, the synthesis employed a Ser/Thr ligation (STL) at a new ligation site combined with classical fragment coupling. This study provides the total synthesis of corramycin and enhances the preparative toolbox of STL in organic synthesis.",10.1021/acs.orglett.4c00774,2024-04-02,0.5832923184911469
Journal of Organic Chemistry,"Convenient Synthesis of 6,6-Bicyclic Malonamides:  A New Class of Conformationally Preorganized Ligands for f-Block Ion Binding","A general synthetic approach was developed for the preparation of a series of 6,6-bicyclic malonamides, a class of ligands that provide a preorganized binding site for f-block ions (particularly trivalent lanthanides). The approach described is convenient to introduce a variety of functional groups at the amide nitrogens to tune the properties of the ligand without altering the preorganized binding. Each of the ten derivatives (that represent a range of functionality, including R = alkyl, hydroxy, phenyl, ester, perfluorocarbon) reported here derives from a single, readily prepared dialdehyde intermediate. This intermediate is converted to the final products via reductive amination with an appropriately functionalized benzylamine, followed by hydrogenolysis and lactam formation. Because derivatization occurs late in the synthesis, the approach is general, requiring only modification of the purification procedures for each new derivative. To aid in the purification of the bicyclic malonamides, we report a novel complexation-based purification method that takes advantage of the high affinity of the ligand for f-block metals.",10.1021/jo0617262,2006-12-01,0.5832916332500869
Journal of Organic Chemistry,Total Synthesis of 15-D<sub>2t</sub>- and 15-<i>epi</i>-15-E<sub>2t</sub>-Isoprostanes,"The first total synthesis of 15-D(2t)-isoprostane is described. (-)-(9S,15S)-15-D(2t)-IsoP 1 and (+)-(11R,15R)-15-epi-15-E(2t)-IsoP 2 have been obtained in 15 steps from orthogonally protected enantiopure bicycle 3. Key features include an easy introduction of the cis side chains via ozonolysis, a highly selective enzymatic chemical differentiation of a non-meso-1,5-diol, and the use of a common synthetic intermediate allowing a stereodivergent approach to the target molecules.",10.1021/jo1000274,2010-03-10,0.583290809644594
Journal of Organic Chemistry,The Synthesis of Sterically Demanding Amino Acid-Derived Cyclic Phosphonamides,"The preparation and utilization of C(2)-symmetric 1,4-diamines in the synthesis of amino acid-derived cyclic phosphonamides 1-3 are described. The 1,4-diamines are synthesized via three methods: (i) amino acid/fumaryl chloride coupling followed by amide reduction, (ii) amino acid/1,4-diamine coupling followed by amide reduction, and (iii) a template-supported ring-closing metathesis/hydrolysis sequence. The pseudo C(2)-symmetric cyclic phosphonamides 1-3 are prepared by condensation of the C(2)-symmetric 1,4-diamines to P(III) centers, followed by oxidation.",10.1021/jo005545q,2000-10-25,0.5832826889113288
European Journal of Organic Chemistry,Total Synthesis of Macrosphelide M from Diacetone Glucose,"Abstract The total synthesis of macrosphelide M is described. The key steps include the preparation of the acid and alcohol fragments from diacetone glucose and ( S )‐malic acid, respectively, followed by Yamaguchi esterification and macrocyclization of the tris‐olefin by ring‐closing metathesis. Finally, one‐pot deprotection of the PMB and TBS groups with TiCl 4 results in the target. The C‐3/C‐4 stereocenters of diacetone glucose are used for the introduction of four stereocenters, whereas the fifth stereocenter is realized from ( S )‐malic acid.",10.1002/ejoc.201101603,2012-03-12,0.5832803679481403
Tetrahedron,Synthetic studies on palytoxin stereocontrolled practical synthesis of the C.23 – C.37 segment,,10.1016/s0040-4039(00)81682-2,1983-01-01,0.5832771293484578
Tetrahedron,Asymmetric synthesis of β-lactams by chiral ester enolate - imine condensation,,10.1016/s0040-4039(00)97603-2,1990-01-01,0.5832757625603471
Journal of Organic Chemistry,Synthetic Studies toward Jatrophane Diterpenes from <i>Euphorbia characias</i>. Enantioselective Synthesis of (−)-15-<i>O</i>-Acetyl-3-<i>O</i>-propionyl-17-norcharaciol,The enantioselective synthesis of (+)-17-norcharaciol is described. An uncatalyzed intramolecular carbonyl-ene reaction and a ring-closing metathesis were used as key C/C-connecting transformations to assemble the trans-bicyclo[10.3.0]pentadecane norditerpenoid core. We also report the evolution of our synthetic strategy toward the fully substituted characiol skeleton and the experiences from this venture.,10.1021/jo802581g,2009-01-13,0.5832721364250463
Organic Letters,Total Synthesis of (±)-Thebainone A by Intramolecular Nitrone Cycloaddition,"Using an intramolecular nitrone cycloaddition and a Heck cyclization as the crucial transformations, a total synthesis of the racemic morphine alkaloid thebainone A was accomplished in 22 steps commencing with isovanillin.",10.1021/acs.orglett.0c00905,2020-04-06,0.5832670000392283
Synthesis,"Practical Synthesis of Optically Pure Methyl (2<i>R</i>,3<i>S</i>)-2,3-Epoxybutanoate via Microbial Asymmetric Reduction of α-Chloroacetoacetate","All articles of this category Asymmetric reduction of ethyl α-chloroacetoacetate ( 3 ) with Baker's yeast followed by treatment with sodium ethoxide afforded a mixture of ethyl (2 R ,3 S )-( 8 ) and (2 S ,3 S )-2,3-epoxybutanoate ( 9 ) ( 8/9 , 85:15), which could be converted into the optically pure methyl (2 R ,3 S )-2,3-epoxybutanoate ( 25 ) via one recrystallization of the brucine salt of the diastereomeric mixture of the corresponding epoxy acid.",10.1055/s-1993-25895,1993-01-01,0.5832665228729
Tetrahedron,Stereospecific synthesis of the lythgoe's ring a aldehyde for the preparation of 1α-hdroxylated tachysterols and calciferols,,10.1016/s0040-4039(00)96052-0,1987-01-01,0.5832660855573017
Synthesis,A New Approach to the Synthesis of Tazobactam Using an Organosilver Compound,"Tazobactam (9) was synthesized in 8 steps from the readily accessible 6-APA. By the first use of silver triazole as reactant, the formation of the isomer 7 was avoided and a total yield of 50%, which was two to three times higher than that of reported procedures for 9, was obtained.",10.1055/s-2004-837299,2005-01-01,0.5832656154326926
Journal of the American Chemical Society,"Asymmetric Total Syntheses of Hetidine-Type C <sub>20</sub> -Diterpenoid Alkaloids: Spirasines V and VI, Spiradine D, and the Proposed Structures of Spirafines II and III","-diterpenoid alkaloids, namely, spirasines V and VI, spiradine D, and the proposed structures of spirafines II and III. Crucial transformations include an Enders asymmetric addition, an oxidative dearomatization induced Diels-Alder cycloaddition, and a MHAT-initiated transannular radical cyclization. The heterocyclic rings were assembled by an efficient reductive cyclization sequence at a late stage. Our approach has enabled the total syntheses of these natural products in 17-20 steps from commercially available starting materials with high enantio- and diastereocontrol.",10.1021/jacs.5c13564,2025-10-15,0.5832651630573489
Tetrahedron,"Novel, green and sustainable route for synthesis of 5-aryl-4-phenyl-1,2,4-triazolidine-3-thiones",,10.1016/j.tetlet.2020.152015,2020-05-14,0.5832648770494316
Tetrahedron,A versatile synthesis of butenolides total synthesis of (+/-)-mintlactone,,10.1016/s0040-4039(00)97172-7,1990-01-01,0.5832524112539167
Tetrahedron,"Improved synthesis of 1,2,4-triazoline-3,5-dione derivatives of ergosterol and a new method for their reconversion to ergosterol",,10.1016/s0040-4039(00)88078-8,1983-01-01,0.5832510808137913
Tetrahedron,Chiral precursors for the synthesis of enantiomerically pure piperidines. Total synthesis of (R)-(-)-coniine,,10.1016/s0040-4039(00)76803-1,1994-04-01,0.5832508505219185
European Journal of Organic Chemistry,"AlCl<sub>3</sub>‐Promoted Facile <i>E</i>‐to‐<i>Z</i> Isomerization Route to (<i>Z</i>)‐2‐Methyl‐1‐buten‐1,4‐ylidene Synthons for Highly Efficient and Selective (<i>Z</i>)‐Isoprenoid Synthesis","Abstract Zr‐catalyzed methylalumination of 3‐butyn‐1‐ols followed by AlCl 3 ‐promoted stereoisomerization at 50 °C for 6 h provides 4‐iodo‐3‐methyl‐3‐buten‐1‐ols 2b and 6 (≥98 % Z configuration) in 87 and 67 % yields, respectively. ( Z )‐1,4‐Diiodo‐2‐methyl‐1‐butene ( 1b ) obtainable by iodination of 2b is a valuable synthon for efficient and selective syntheses of ( Z )‐alkene‐containing isoprenoids.(© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2009)",10.1002/ejoc.200801188,2009-01-28,0.5832493005613337
Journal of Organic Chemistry,Divergent Synthesis of 3-(Indol-2-yl)quinoxalin-2-ones and 4-(Benzimidazol-2-yl)-3-methyl(aryl)cinnolines via Polyphosphoric Acid (PPA)-Mediated Intramolecular Rearrangements of 3-(Methyl/aryl(2-phenylhydrazono)methyl)quinoxalin-2-ones,"Herein, we report a polyphosphoric acid (PPA)-mediated divergent metal-free operation to access a diverse collection of 3-(indol-2-yl)quinoxalin-2-ones and 4-(benzimidazol-2-yl)-3-methylcinnolines in moderate to excellent overall yields. The described process involves two distinct, and competing rearrangements of 3-(methyl(2-phenylhydrazono)methyl)quinoxalin-2-ones, namely [3,3]-sigmatropic Fischer rearrangement with the formation of an indole ring to produce 3-(indol-2-yl)-quinoxalin-2-ones, and Mamedov rearrangement with simultaneous construction of benzimidazole and cinnoline rings to form the new biheterocyclic system─4-(benzimidazol-2-yl)-3-methylcinnolines. The reaction mechanism of both rearrangement channels is explored by extensive dispersion-corrected DFT calculations. It is partcularly remarkable that when 3-(aryl(2-phenylhydrazono)methyl)quinoxalin-2-ones is used, instead of 3-(methyl(2-phenylhydrazono)methyl)quinoxalin-2-ones, reactions proceed regioselectively with the formation of only rearrangement products─4-(benzimidazol-2-yl)-3-arylcinnolines with high yields. This operationally simple protocol enables a rapid access to these scaffolds and is compatible with a wide scope of starting materials. In addition, the new rearrangement found features a promising approach for the design of unique compound libraries for drug design and discovery programs.",10.1021/acs.joc.3c01626,2023-11-30,0.5832346607933961
Organic Process Research & Development,Dimethyltitanocene:  From Millimole to Kilomole,"The process development of a dimethyltitanocene-mediated ester olefination is described. The synthetic challenges and stability issues involving large-scale production of dimethyltitanocene are documented, and the optimization of the ester olefination is detailed. The process described was used to make hundreds of kilograms of an advanced intermediate for aprepitant (Emend).",10.1021/op034180j,2004-03-01,0.5832339454797748
Tetrahedron,"The synthesis of 4-amino-8-(β--ribofuranosyl)aminopyrimido[5,4-]pyrimidine from a purine nucleoside: a novel rearrangement of the purine ring",,10.1016/s0040-4039(01)96329-4,1973-01-01,0.583232211178272
Synlett,Total Synthesis of (±)-3-Hydroxy-β-ionone through a Ring-Closing Enyne Metathesis,"The total synthesis of (±)-3-hydroxy-β-ionone, a bisnor­sesquiterpene having allelopathic activity, has been accomplished employing an enyne metathesis for the construction of the C1-C8 segment and two-carbon elongation via a nitrile oxide-alkene [3+2] cycloaddition as the key steps.",10.1055/s-0031-1290353,2012-02-13,0.5832288302776936
Tetrahedron,Azinothricin synthetic studies. 1. Efficient asymmetric synthesis of (3R)- and (3S)-piperazic acids,,10.1016/s0040-4039(00)60838-9,1992-01-01,0.5832247174358609
Tetrahedron,Practical and efficient preparation of the chiral 4-bromotryptophan derivative by Rh-catalyzed hydrogenation,,10.1016/j.tetlet.2019.151498,2019-12-09,0.5832197687360827
Tetrahedron,"An efficient and general methodology for the synthesis of the hetes: synthesis of (±)-5-hydroxy-6-trans-8,11,14-cis-eicosatetraenoic acid (5-hete)",,,1985-01-01,0.5832140807811355
Tetrahedron,"An efficient and general methodology for the synthesis of the hetes: synthesis of (±)-5-hydroxy-6-trans-8,11,14-cis-eicosatetraenoic acid (5-hete)",,10.1016/s0040-4039(00)98858-0,1985-01-01,0.5832140807811355
Journal of Organic Chemistry,"Stereoselective Synthesis of Polyhydroxylated Indolizidines from γ-Hydroxy α,β-Unsaturated Sulfones","The polyhydroxylated indolizidines castanospermine and swainsonine as well as some of their stereoisomers are powerful glycosidase inhibitors. An efficient and stereochemically flexible synthesis of racemic 1,7,8-trihydroxylated and 1,6,7,8-tetrahydroxylated indolizidines (castanospermine stereoisomers) from readily available N-substituted γ-oxygenated α,β-unsaturated sulfones 3 and 4 has been developed. The construction of the bicyclic skeleton of 1-hydroxyindolizidine has been accomplished by intramolecular conjugate addition of the nitrogen moiety of 3 and 4 to the α,β-unsaturated sulfone unit to give the pyrrolidine intermediates 5 and 6, followed by formation of the C(7)−C(8) bond by intramolecular acylation (or alkylation) of the α-sulfonyl carbanion. The stereoselectivity of the pyrrolidine synthesis was highly dependent on the bulkiness of the γ-oxygenated function; thus, the free alcohols gave predominantly cis -pyrrolidines while the OTIPS derivatives led to the trans isomers. After straightforward functional group transformations, the removal of the sulfonyl group at C(8) either by Julia reaction or by basic elimination (depending on the substrate used) afforded the key C(7)C(8) unsaturated indolizidines 10, 22, 30, and 31, whose stereoselective dihydroxylations with OsO 4 gave a variety of cis C(1)C(8a) and trans C(1)C(8a) trihydroxylated and tetrahydroxylated indolizidines, among which (±)-1,7-di- epi -castanospermine and (±)-1,8-di- epi -castanospermine have been reported for the first time.",10.1021/jo972167p,1998-04-17,0.5832134379937254
Tetrahedron,Stereoselective synthesis of (η6-arene)chromium complexes possessing chiral amine and hydroxy groups: chiral ligands in asymmetric synthesis,,10.1016/0040-4039(91)80041-4,1991-01-01,0.5832098558526816
Synlett,Efficient Total Synthesis of (±)-Isoguaiacin and (±)-Isogalbulin,"1-Arylnaphthalene lignans such as (–)-isoguaiacin and (–)-isogalbulin have been reported to exhibit notable biological properties. While (–)-isoguaiacin has not been previously synthesized, syntheses of (–)-isogalbulin are generally long and produce a mixture of stereoisomers. We herein present the efficient total synthesis of (±)-isoguaiacin and (±)-isogalbulin in seven and eight steps with an overall yield of 46% and 36%, respectively. The reported approach harnesses a hydrogenolysis reaction in acidic conditions, to convert a furan into an arylnaphthalen structure.",10.1055/s-0036-1588788,2017-04-19,0.583207069135167
Organic Process Research & Development,A New Efficient Route to<i>Tolterodine</i>,"Tolterodine, an important urological drug, can be conveniently prepared starting from 1-[2-hydroxy-5-methyl)phenyl]-1-phenylethylene, accessible in high yield by alumina-promoted ortho alkenylation of p -cresol with phenylacetylene. The hydroformylation of this olefin, catalyzed by rhodium complexes both in homogeneous or in aqueous biphasic system, affords the desired linear aldehyde in about 80−90% yield. The reductive amination of this aldehyde, in the presence of HN( i Pr) 2 and Pd/C (5%) as the catalytic precursor at 4 atm H 2 and 48 °C, produces directly tolterodine in more than 90% yield. Some experiments of enantioselective hydroformylation of 1-[2-hydroxy-5-methyl)phenyl]-1-phenylethylene catalyzed by Rh(CO) 2 acac/( S, R )-Binaphos and other enantiopure ferrocenyldiphosphines afforded only low yields of the expected chiral aldehyde; unfortunately, the achieved ee did not exceed 8%.",10.1021/op020014k,2002-05-18,0.5832059713372734
Angewandte Chemie International Edition,A Potent and Selective Janus Kinase Inhibitor with a Chiral 3D‐Shaped Triquinazine Ring System from Chemical Space,"The generated databases (GDBs) enumerate billions of possible molecules following simple rules of chemical stability and synthetic feasibility. Exploring the GDBs shows that many chiral, 3D-shaped ring systems, often containing quaternary centers, have never been exploited for drug design. Shown herein is that such ring systems can be useful for medicinal chemistry by using the example of the enantioselective synthesis of triquinazine, a novel chiral piperazine analogue derived from angular triquinane. It is used to design a nanomolar and selective inhibitor of Janus Kinase 1 and is related to the marketed drug Tofacitinib, which is useful for treating autoimmune diseases.",10.1002/anie.202012049,2020-09-28,0.5832039930447125
Green Chemistry,The synthesis of new 8-imino-1-one acridine derivatives catalyzed by a calix[4]arene mono-acid core,Mono-acid incorporated calix[4]arene has been successfully used as the catalyst for the synthesis of 8-imino-1-one acridines.,10.1039/c6gc02144a,2016-01-01,0.5832003438606234
Journal of Organic Chemistry,Stereoselective Synthesis and Determination of the Cytotoxic Properties of Spicigerolide and Three of Its Stereoisomers,"Stereoselective syntheses of the naturally occurring, cytotoxic lactone spicigerolide and three nonnatural stereoisomers thereof are described. The commercially available sugar l-rhamnose was in all cases the chiral starting material. Key steps in each of these syntheses were asymmetric Brown allylations and ring-closing metatheses. The cytotoxic activities of the four lactones against a range of tumoral lines were then determined.",10.1021/jo034470y,2003-06-13,0.5831990564286078
Journal of Organic Chemistry,Total Synthesis of Zaragozic Acid A (Squalestatin S1). Synthesis of the Relay Compound,"Compound 2 has been prepared from the 1,6-anhydropyranohexose 3 . The key process for elaborating the 1,7-dioxabicyclo[3.2.1]octane core of the zaragozic acids is addition of an organometallic reagent to lactone 6 and treatment of the resulting 1,2,3-trihydroxy-6-oxo ethylene acetal with acid. Use of the cerium(III) reagent of 4-bromo-1-butene in this process provided 7 in excellent yield, unaccompanied by the isomeric 1,6-anhydropyranose isomer. The remaining two carboxy groups of the zaragozic acid core were added by addition of the lithium enolate of 8 to formaldehyde, to obtain 9, and cerium(III)-mediated addition of vinyllithium to ketone 10 . The latter addition was shown by 2D 1 H NMR experiments to provide the relative configuration found in the zaragozic acids. Similar stereoselective additions were observed with 2-furyllithium and (5-methyl-2-furyl)lithium, but the resulting adducts are resistant to ozonolysis. The synthesis of 2 completes a total synthesis of zaragozic acid A (squalestatin S1) ( 1 ).",10.1021/jo961534e,1996-01-01,0.5831937502195117
Organic Letters,Modular Route to Azaindanes,"A convergent radical based route to azaindanes is described, relying on the degenerative addition transfer of various substituted S-(pyridylmethyl)-O-ethyl dithiocarbonates (xanthates) to functional alkenes followed by radical cyclization onto the pyridine ring activated by protonation with trifluoroacetic acid. In one case, a richly decorated cyclohepta[b]pyridine could be assembled swiftly by allowing the first adduct to N-phenylmaleimide to undergo addition to N-allylphthalimide prior to cyclization.",10.1021/acs.orglett.7b01772,2017-07-12,0.5831921692554788
Angewandte Chemie International Edition,Total Synthesis of 1‐<i>O</i>‐Methyllateriflorone,"The unique spiroxalactone framework of lateriflorone (1) consists of a prenylated dihydrobenzoquinone moiety and a trioxatetracyclotetradecane system. A tandem Claisen rearrangement/Diels–Alder cascade was the key step in the synthesis of the complex tetradecane system, which was then used to prepare 1-O-methyllateriflorone (2).",10.1002/anie.200351805,2003-09-15,0.5831882589974982
Synthesis,Synthesis of N-(Triisopropylsilyl)- and N-(tert-Butyldimethylsilyl)aldimines and Their Application in the Synthesis of β-Lactams,"All articles of this category A new and efficient synthesis of N -(TIPS)imines and N -(TBDMS)-imines starting from enolizable and non-enolizable aldehydes is described. We tested the reactivity of these imines in the preparation of β -lactams. N -(TBDMS)imines effectively give N (-TBDMS)azetidinones with a trans stereochemistry of the ring substituents, complementing N -(TMS)imines which instead afford cis β -lactams. In contrast, N -(TIPS)imines react with ester enolates in few cases because of the extremely low rate of the ring-closure step, so that a decomposition of enolates occurred. imines - β -lactams - nucleophilic addition - ester enolates - silylimines",10.1055/s-1997-1276,1997-08-01,0.5831875723623592
Tetrahedron,"Cobalt-catalyzed mono-coupling of R 3 SiCH 2 MgCl with 1,2-dihalogenoethylene: a general route to γ-substituted ( E )-allylsilanes",,10.1016/j.tetlet.2004.04.098,2004-05-13,0.5831860955368062
Tetrahedron,"Cobalt-catalyzed mono-coupling of R3SiCH2MgCl with 1,2-dihalogenoethylene: a general route to $gamma;-substituted (E)-allylsilanes",,10.1016/s0040-4039(04)00889-5,2004-05-26,0.5831860955368062
Synthesis,"Synthesis of Aryl-Substituted 3,3a,4,5-Tetrahydropyrrolo[1,2-a] quinolin-1(2H)-ones and 2,3,4,4a,5,6-Hexahydro-1H-pyrido[1,2-a]quinolin-1-ones","A new route to the title benzo-fused angular tricyclic amides 3,3a,4,5-tetrahydropyrrolo- and 2,3,4,4a,5,6-hexahydro-1H-pyrido[1,2-a]quinolin-1-ones is reported from 1-(tert-butyl) 6-ethyl 3-oxohexanedioate and 1-(tert-butyl) 7-ethyl 3-oxoheptanedioate. Alkylation of these β-keto diesters with a series of 2-nitrobenzyl bromides followed by acid hydrolysis and decarboxylation gives ethyl 6-(2-nitrophenyl)-4-oxohexanoates and ethyl 7-(2-nitrophenyl)-5-oxoheptanoates, respectively. Reductive amination under hydrogenation conditions followed by ester hydrolysis and condensative ring closure affords the final lactam products. The reactions proceed cleanly and only two chromatographic purifications are required.",10.1055/s-0037-1609940,2018-09-05,0.5831665808991957
Tetrahedron,"A total synthesis of (±)-iso-ochracinic acid, a hydroxy phthalide from",,10.1016/s0040-4039(01)83561-9,1977-01-01,0.5831581685225423
Synlett,Recent Developments in the Synthesis of Nitrogen-Containing Heterocycles through C–H/N–H Bond Functionalizations and Oxidative Cyclization,"The synthesis and structure of nitrogen-containing heterocycles are fascinating because these compounds have a great richness of structural, physicochemical, and biological properties. Therefore, the development of improved ways for the synthesis of polyfunctional nitrogen-containing heterocycles continues to be a challenging goal. This account describes developments in the discovery of C–H/N–H bond functionalization and oxidative cyclization procedures for the synthesis of nitrogen-containing heterocycles (aziridines, indoles, indolizines, triazoles, imidazoles, oxazoles, thiazoles, quinoxalines, triazines, and pyridines) in our laboratories during the last 15 years. 1 Introduction 2 Synthesis of Aziridines 3 Synthesis of Indoles and Indolizines 4 Synthesis of Triazoles 5 Synthesis of Imidazoles 6 Synthesis of Oxazoles and Thiazoles 7 Synthesis of Quinoxalines, Triazines, and Pyridines 8 Conclusion and Outlook",10.1055/s-0037-1611476,2019-02-22,0.5831549015224763
Journal of the American Chemical Society,"A General Strategy for the Synthesis of Cladiellin Diterpenes:  Enantioselective Total Syntheses of 6-Acetoxycladiell-7(16),11-dien-3-ol (Deacetoxyalcyonin Acetate), Cladiell-11-ene-3,6,7-triol, Sclerophytin A, and the Initially Purported Structure of Sclerophytin A","Enantioselective total syntheses of the cladiellin diterpenes, 6-acetoxycladiell-7(16),11-dien-3-ol (deacetoxyalcyonin acetate, 6), cladiell-11-ene-3,6,7-triol (1), sclerophytin A (8), and tetracyclic diether 7, have been achieved by differential elaboration of tricyclic allylic alcohol 57. The central step in these syntheses is acid-promoted condensation of alpha,beta-unsaturated aldehydes 45, 69 or 87, and cyclohexadienyl diol 44 to form, with complete stereocontrol, the hexahydroisobenzofuran core and five stereocenters of these cladiellin diterpenes. These syntheses also feature stereospecific photolytic deformylation of beta,gamma-unsaturated aldehydes 46, 70, and 71 to remove the extraneous carbon introduced in the Prins-pinacol step; chemo- and stereoselective hydroxyl-directed epoxidation of 49, 72, and 90 followed by regioselective reductive opening with hydride to install the C3 tertiary hydroxyl group; and a diastereoselective Nozaki-Hiyama-Kishi cyclization of iodoaldehyde 56 to forge the oxacyclononane ring and the C6 hydroxyl stereocenter. Other key transformations include chemo- and stereoselective hydroxyl-directed epoxidation of tricyclic allylic alcohol 57 followed by regioselective reductive opening with hydride to install the C7 tertiary hydroxyl center of 1 and 8; chemo-, regio-, and stereoselective intramolecular oxymercuration-reductive demercuration of dienyl diol 62 to form the bridging tetrahydropyran ring of tetracyclic diether 7; and photochemical isomerization of the endocyclic double bond of 92 and 1 to give exocyclic congeners 7 and 8. The absolute stereochemistry of the synthetic products originates from two chiral nonracemic starting materials, (S)-(+)-carvone and (S)-(-)-glycidol. These syntheses define a versatile and concise strategy for the total synthesis of cladiellin diterpenes and provide additional illustrations of the uncommon utility of pinacol-terminated cationic cyclizations for the stereocontrolled synthesis of complex oxacyclic products.",10.1021/ja016351a,2001-08-22,0.5831538181658139
Synlett,New Synthesis of Carbazoles from Novel<i>exo</i>-2-Oxazolidinone Dienes,"All articles of this category A new synthesis of carbazoles, via regioselective Diels-Alder reaction of novel exo -2-oxazolidinone dienes 1 , is described. Cyclization with palladium acetate of the intermediate diaryl amines, obtained by a one-pot three-step procedure from the cycloadducts, yielded the desired substituted carbazoles. carbazoles - exo -2-oxazolidinone dienes - Diels-Alder - palladium",10.1055/s-1998-1571,1998-01-01,0.5831526110082453
Organic Letters,"Total Synthesis of the Cyclic Depsipeptide YM-280193, a Platelet Aggregation Inhibitor","The first total synthesis of YM-280193, a cyclic depsipeptide that inhibits the ADP-induced aggregation of human platelets, is described. The monomer and dipeptide fragments were prepared using conventional chemistry and subsequently assembled by Fmoc-solid-phase peptide synthesis (Fmoc-SPPS). A late-stage novel bis-alkylation-elimination of cysteine on-resin was employed to introduce the unnatural N-methyldehydroalanine moiety. The final step involved execution of a key macrolactamization reaction between the hindered unnatural N,O-dimethylthreonine and β-hydroxyleucine residues.",10.1021/ol503507g,2015-01-15,0.5831493834298348
Journal of Organic Chemistry,Synthesis of 3-Alkoxymethylcoumarin from 3-Cyanochromene via a Novel Intermediate 2-Phenylimino-3-alkoxymethylchromene,"In this paper a concise, efficient, and environmentally benign method for the synthesis of 3-alkoxymethylcoumarin is described. From the reaction of 3-cyanochromene with an alkoxide and arylamine in THF, (Z)-2-phenylimino-3-alkoxymethylchromene was obtained as a novel intermediate via an isomerization of the double bond, a 1,2-addition of alkoxide, a Michael-type addition of aniline, an another isomerization of double bond and an elimination of ammonia. Subsequently, the intermediate was converted into the desired coumarin by treatment with 15% HCl in THF in good yield.",10.1021/jo9015634,2009-10-23,0.5831449363280589
Organic Letters,Total Synthesis of Proximicin A−C and Synthesis of New Furan-Based DNA Binding Agents,"The total synthesis of the natural occurring polyamides proximicin A-C (3-5) has been accomplished. A short and efficient synthesis of a thus far unknown 4-amino-2-furan carboxylic acid was developed. Furthermore, this unique heterocyclic gamma-amino-acid was used for the synthesis of a new class of AT-selective DNA-binding agents derived from the natural products combining structural features of the proximicins with those from the known DNA-binding natural products netropsin (1) and distamycin (2).",10.1021/ol901003p,2009-06-11,0.5831425247259261
Tetrahedron,Steroids CCLXVIII. Steroids of unnatural configuration: A new route to 9β-10α-19-norsteroids,,10.1016/0040-4039(64)83087-2,1964-01-01,0.5831420253689071
Synthesis,Studies toward the Total Synthesis of (-)-Dictyostatin: Stereoselective Preparation of the C1-C10 Fragment,"The efficient synthesis of the C1-C10 fragment of (-)-dictyostatin has been achieved by Evans-Tischenko reduction of a β-hydroxy ketone, followed by cross metathesis and Z-olefination. The β-hydroxy ketone is easily synthesized diastereoselectively by allylation and dihydroxylation of an alcohol.",10.1055/s-2007-983871,2007-09-01,0.5831401002024673
Journal of the American Chemical Society,Enantioselective Total Synthesis of Fortalpinoid Q via a TEMPO<sup>+</sup>BF<sub>4</sub><sup>–</sup>-Mediated Dehydrative Nazarov Cyclization,"The family of Cephalotaxus diterpenoids represents a captivating class of natural products that are of significant interest from both structural and biological perspectives within our community. Here we wish to report a 15-step, enantioselective total synthesis of the Cephalotaxus diterpenoid fortalpinoid Q. Our approach highlights (1) a Jacobsen’s catalytic enantioselective Claisen rearrangement that enabled the single-step formation of two vicinal stereogenic centers, including an all-carbon quaternary center; (2) a mild, oxoammonium salt (TEMPO + BF 4 – )-promoted dehydrative Nazarov cyclization that swiftly forged the crucial cyclopentadiene moiety via an unfunctionalized tertiary divinyl carbinol (TDC) substrate; and (3) a facile aldol-lactonization cascade that ultimately resolved the last obstacle in the synthesis.",10.1021/jacs.5c00319,2025-03-10,0.5831386061398208
Journal of the American Chemical Society,Highly Convergent Total Synthesis of (+)-Lithospermic Acid via a Late-Stage Intermolecular C−H Olefination,"The total synthesis of (+)-lithospermic acid is reported, which exploits two successive C-H activation reactions as key steps. Rh-catalyzed carbene C-H insertion reaction utilizing Davies's catalyst was used to forge dihydrobenzofuran core, and a late-stage intermolecular C-H olefination coupled the olefin unit with the dihydrobenzofuran core to construct the molecule in a highly convergent manner.",10.1021/ja2010225,2011-03-28,0.5831357007745958
Journal of Organic Chemistry,"Palladium-Mediated Oxidative Annulation of δ-Indolyl-α,β-Unsaturated Compounds toward the Synthesis of Cyclopenta[<i>b</i>]indoles and Heterogeneous Hydrogenation To Access Fused Indolines","The cyclopenta[ b]indole moiety represents a key skeletal unit in several natural and synthetic compounds that exhibit diverse biological properties. We described herein a two-step sequence for synthesizing cyclopenta[ b]indoles with great structural diversity in overall yields up to 37%. The key step was a palladium-catalyzed oxidative annulation of 3-alkylindoles (Fujiwara-Moritani reaction). The obtained cyclopenta[ b]indoles were used as substrates in heterogeneous hydrogenation reactions to afford new fused indolines in moderate yields. An acid-catalyzed intramolecular cyclization of three such indolines gave tetracyclic lactams in 89, 90, and 61% yields.",10.1021/acs.joc.9b00505,2019-04-02,0.5831333878340226
Journal of the American Chemical Society,"Discovery of (<i>E</i>)<i>-</i>9,10-Dehydroepothilones through Chemical Synthesis:  On the Emergence of 26-Trifluoro-(<i>E</i>)-9,10-dehydro-12,13-desoxyepothilone B as a Promising Anticancer Drug Candidate","We provide a full account of the discovery of the (E)-9,10-dehydro derivatives of 12,13-desoxyepothilone B (dEpoB), a new class of antitumor agents with promising in vivo preclinical properties. The compounds, which are to date not available by modification of any of the naturally occurring epothilones, were discovered through total chemical synthesis. We describe how our investigations of ring-closing metathesis reactions in epothilone settings led to the first and second generation syntheses of (E)-9,10-dehydro-12,13-desoxyepothilone congener 6. With further modifications, the synthesis was applied to reach a 26-trifluoro derivative compound (see compound 7). To conduct such studies and in anticipation of future development needs, the total synthesis which led to the initial discovery of compound 7 was simplified significantly. The total synthesis methodology used to reach compound 7 was then applied to reach more readily formulated compounds, bearing hydroxy and amino functionality on the 21-position (see compounds 45, 62, and 63). Following extensive in vitro evaluations of these new congeners, compound 7 was nominated for in vivo evaluations in xenograft models. The data provided herein demonstrate a promising therapeutic efficacy, activity against large tumors, nonrelapseability, and oral activity. These results have identified compound 7 as a particularly promising compound for clinical development. The excellent, totally synthetic, route to 7 makes such a program quite feasible.",10.1021/ja046992g,2004-08-13,0.583132788446181
Journal of Organic Chemistry,Free Radical Studies and Solutions to the Synthesis of (+)-Cyclophellitol,"d -Xylose serves as a starting material for approaches to the synthesis of the glucosidase inhibitors, (+)-cyclophellitol ( 1 ) and (+)-epi-cyclophellitol ( 2 ). An investigation of the cyclization of diastereomeric oxiranyl radicals to achieve this goal was moderately successful with the diastereomer that would have led to epi-cyclophellitol undergoing cyclization. An alternative route to cyclophellitol from d -xylose employed Grubbs' ring closure metathesis and radical transformations to complete the synthesis.",10.1021/jo981211d,1998-10-01,0.5831301252799905
Synlett,"A Comparative Study of theSynthesis of C<sub>2</sub>-Symmetric Chiral 2,2′-Biaziridinyls","Two comparative synthetic routes to new enantiomeric C2-symmetric Boc-protected biaziridinyls from tartaric ester were studied. Simplicity, high enantiomeric purity and high chemical yield of the target compound characterize the proposed methods. Also, unprotected biaziridinyl was synthesized and fully characterized.",10.1055/s-2003-39303,2003-01-01,0.5831293935029911
Journal of the American Chemical Society,"Catalytic Asymmetric Intramolecular Aminopalladation:  Enantioselective Synthesis of Vinyl-Substituted 2-Oxazolidinones, 2-Imidazolidinones, and 2-Pyrrolidinones","A new catalytic asymmetric synthesis of five-membered nitrogen heterocycles is reported. This synthesis employs ferrocenyloxazoline palladacycles (FOP trifluoroacetate catalysts) 2 and 4 and proceeds by a catalytic cycle involving Pd(II) intermediates. For example, prochiral (Z)-4-acetoxy-2-buten-1-ols are condensed with an arylsulfonyl isocyanate and the derived allylic N-arylsulfonylcarbamates cyclize in situ upon addition of 0.5-5 mol % of 2 or 4 to form 4-vinyloxazolidin-2-ones 6, 13, and 15 in high yield and 89-99% ee. The related 2-pyrrolidinone 19 and 2-imidazolidinone 18 are prepared in similar fashion. Pyrrolidinone 19 can be converted in two steps to the unnatural enantiomer of the GABA inhibitor vigabatrin 20.",10.1021/ja017198n,2001-12-04,0.5831284634673249
Tetrahedron,General route for the synthesis of mono N-alkylated derivatives of tetraazamacrocycles,,10.1016/s0040-4039(00)74848-9,1991-01-01,0.5831283454935646
Synlett,Total Syntheses of Spinosyn A,"Spinosyn A is an important polycyclic natural product with impressive insecticidal activity and has been used worldwide in agriculture as the major component of Spinosad. Herein, four chemical total syntheses of spinosyn A are summarized. Its biosynthesis and a chemoenzymatic total synthesis are discussed as well. 1 Biosynthesis 2 The Evans Synthesis 3 The Paquette Synthesis 4 The Roush Synthesis 5 The Liu Synthesis 6 The Dai Synthesis 7 Conclusions",10.1055/s-0037-1610249,2018-09-07,0.5831256409663202
Journal of Organic Chemistry,Enantioselective Synthesis of Indoloquinolizidines via Asymmetric Catalytic Hydrogenation/Lactamization of Imino Diesters,"We have developed a highly efficient cascade sequence for asymmetric synthesis of indoloquinolizidines with absolute control of cis-H2/H12b relative geometry in good to excellent yields and excellent enantioselectivities. This cascade was triggered by the Ru(II)-TsDPEN-catalyzed asymmetric transfer hydrogenation of imino diesters, with subsequent spontaneous lactamization with discrimination between the two diastereotopic 2-alkoxy-2-oxoethyl groups. The synthetic utility of this strategy was demonstrated by the asymmetric preparation of dihydrocorynantheol, geissoschizol, and isogeissoschizol.",10.1021/jo4020547,2013-11-06,0.5831255605219385
Journal of Organic Chemistry,"One-Pot Diastereoselective Synthesis of Pyrrolopiperazine-2,6-diones by a Ugi/Nucleophilic Substitution/N-Acylation Sequence","The diastereoselective synthesis of two families of pyrrolopiperazine-2,6-diones is presented. These compounds were prepared by one-pot Ugi/nucleophilic substitution/N-acylation/debenzoylation/(elimination) sequences. This novel route provides straightforward access to a wide variety of pyrrolopiperazine-2,6-diones with high chemical yields and complete diastereoselectivities. The proposed synthetic strategy poses a significant improvement compared to the syntheses of pyrrolopiperazine-2,6-diones previously described, as it allows introduction of different substituents to the C4 position and the diastereoselective generation of a new stereogenic center on the bridgehead carbon (C8a).",10.1021/acs.joc.2c00694,2022-06-27,0.5831238225258598
Organic Letters,Formal [4 + 2]-Annulation of Chiral Crotylsilanes:  Synthesis of the C19−C28 Fragment of Phorboxazoles,A stereoselective synthesis of the C19-C28 fragment of phoborxazole A and B is described. The key step is an enantioselective [4 + 2]-annulation of a crotylsilane 10 with a propargylic aldehyde 11 affording a functionalized dihydropyran 12. A solvent-dependent stereoselective epoxidation of dihydropyrans is also documented.,10.1021/ol015893u,2001-04-28,0.5831211854320968
Synthesis,Atroposelective Construction of Tetrasubstituted Axially Chiral Alkene Frameworks,"Abstract The construction of axially chiral alkene frameworks is currently one of hottest topics in the field of organic synthetic chemistry. Compared to traditional axially chiral molecules, such as biaryls, heterobiaryls, and anilides, the synthesis of axially chiral alkenes is far more challenging, especially for acyclic tetrasubstituted alkene analogues. In this review, we summarized the development of strategies for the synthesis of tetrasubstituted axially chiral alkene analogues, including asymmetric difunctionalization, C–H functionalization, cross-coupling, (dynamic) kinetic resolution, and asymmetric allylic substitution-isomerization. 1 Introduction 2 Synthesis of Cyclic Tetrasubstituted Axially Chiral Alkenes 3 Synthesis of Acyclic Tetrasubstituted Axially Chiral Alkenes 4 Summary and Outlook",10.1055/a-2230-0759,2023-12-14,0.583120710179622
Tetrahedron,Total synthesis of amorfrutin A via a palladium-catalyzed migratory prenylation–aromatization sequence,,10.1016/j.tetlet.2011.11.019,2011-11-16,0.5831205453384267
European Journal of Organic Chemistry,Total Synthesis of Calothrixins A and B by Palladium‐Catalyzed Tandem Cyclization/Cross‐Coupling Reaction of Indolylborate,"Abstract The palladium‐catalyzed tandem cyclization/cross‐coupling reaction of triethyl(indol‐2‐yl)borate with vinyl bromide was successfully used in the concise total synthesis of the indolophenanthridine alkaloids, calothrixins A and B.",10.1002/ejoc.201200657,2012-07-26,0.5831129666582893
Organic Letters,An Oxidopyrylium Cyclization/Ring-Opening Route to Polysubstituted α-Hydroxytropolones,"α-Hydroxytropolones are a class of molecules with therapeutic potential against several human diseases. However, structure-activity relationship studies on these molecules have been limited due to a scarcity of efficient synthetic methods to access them. It is demonstrated herein that α-hydroxytropolones can be generated through a BCl(3)-mediated ring-opening/aromatization/demethylation process on 8-oxabicyclo[3.2.1]octenes. Used in conjunction with an improved method based on established oxidopyrylium dipolar cycloadditions, several polysubstituted α-hydroxytropolones can be accessed in three steps from readily available α-hydroxy-γ-pyrones.",10.1021/ol302892g,2012-11-20,0.5831055563442568
Organic Process Research & Development,"Expedient Asymmetric Synthesis of (<i>S</i>)-2-Amino-4,4,4-trifluorobutanoic Acid via Alkylation of Chiral Nucleophilic Glycine Equivalent","Here we disclose a practical asymmetric synthesis of an enantiomerically 97.8% ee pure N -Fmoc derivative of ( S )-2-amino-4,4,4-trifluorobutanoic acid performed on >10 g scale of the target product. The method is based on alkylation (CF 3 –CH 2 –I) of a new generation of a chiral nucleophilic equivalent conducted at ambient temperature with an excellent stereochemical outcome. The developed protocol does not require any chromatographic separations and includes only one purification step via recrystallization of the final product.",10.1021/acs.oprd.8b00404,2019-01-16,0.583105010643733
Synlett,Enantiospecific First Total Synthesis of ent-Allothapsenol,"The enantiospecific first total synthesis of the enantiomer of the irregular sesquiterpene from Ligusticumgrayi allo­thapsenol, starting from the readily available monoterpene ( R )-carvone, is described, which confirmed the assumed absolute configuration of the natural product.",10.1055/s-0031-1290527,2012-03-29,0.5830928643930606
Synthesis,"Synthesis of Tricyclic 1,2,3-Triazolopyridines","Novel tricyclic triazolopyridines were prepared in two steps from the requisite bicyclic 2-ketopyridines. In order to examine the scope of the process, a reliable route to the 2,3-dihydro-1,5-naphthyridin-4(1 H )-one, 7,8-dihydro-5 H -pyrido[3,2- b ]azepin-9(6 H )-one, 7,8-dihydrooxepino[3,2- b ]pyridin-9(6 H )-one, and 7,8-dihydro-5 H -pyrido[3,2- c ]azepin-9(6 H )-one scaffolds was also established.",10.1055/s-0034-1379932,2015-06-24,0.5830921208802903
Tetrahedron,"An efficient and one-pot green synthesis of novel 6-oxo-7-aryl-6,7-dihydrochromeno pyrano[2,3-b]pyridine derivatives",,10.1016/j.tetlet.2018.08.038,2018-08-22,0.5830899723347367
Angewandte Chemie International Edition,"TiCl<sub>3</sub>‐Mediated Synthesis of 2,3,3‐Trisubstituted Indolenines: Total Synthesis of (+)‐1,2‐Dehydroaspidospermidine, (+)‐Condyfoline, and (−)‐Tubifoline","-mediated reductive cyclization of tetrasubstituted alkenes bearing a 2-nitrophenyl substituent. The proof of concept is demonstrated firstly by accomplishing a concise total synthesis of (+)-1,2-dehydroaspidospermidine featuring a late-stage application of this key transformation. A sequence of reduction of nitroarene to nitrosoarene followed by 6π-electron-5-atom electrocyclization and a 1,2-alkyl shift of the resulting nitrone intermediate was proposed to account for the reaction outcome. A subsequent total synthesis of (+)-condyfoline not only illustrates the generality of the reaction, but also provides a mechanistic insight into the nature of the 1,2-alkyl shift. The exclusive formation of (+)-condyfoline indicates that the 1,2-alkyl migration follows a concerted Wagner-Meerwein pathway, rather than a stepwise retro-Mannich/Mannich reaction sequence. Conditions for almost quantitative conversion of (+)-condyfoline to (-)-tubifoline by way of a retro-Mannich/1,3-prototropy/transannular cyclization cascade are also documented.",10.1002/anie.202005380,2020-05-16,0.5830880693698836
Journal of Organic Chemistry,Reaction of Bromomethylazoles and Tosylmethyl Isocyanide. A Novel Heterocyclization Method for the Synthesis of the Core of Marine Alkaloids Variolins and Related Azolopyrimidines,"A novel and efficient synthesis of the pyrido[3',2':4,5]pyrrolo[1,2-c]pyrimidine system, the heterocyclic core of the variolin family of marine alkaloids, is described. The route involves the reaction of 3-bromo-2-(bromomethyl)pyrrolo[2,3-b]pyridine and tosylmethyl isocyanide (TosMIC) under phase-transfer conditions. This unprecedented reaction was also used to synthesize a series of new methoxycarbonyl azolopyrimidines by reaction of TosMIC with bromomethylindoles, bromomethylbenzimidazole, and bromomethylpyrazole. Hydrolysis and decarboxylation of 5-bromo-7-methoxycarbonylpyrido[3',2':4,5]pyrrolo[1,2-c]pyrimidine obtained by this heterocyclization process and installation of the pyrimidine moiety in the C5 position open an alternative approach to complete a total synthesis of variolin B.",10.1021/jo0358168,2004-06-29,0.5830814400873156
Tetrahedron,AlCl3 induced C-arylation/cyclization in a single pot: a new route to benzofuran fused N-heterocycles of pharmacological interest,,10.1016/j.tetlet.2011.12.096,2011-12-31,0.5830759608016063
Tetrahedron,"A highly enantioselective synthesis of (R)- and (S)-5,7-odimethyleucomol",,10.1016/s0040-4039(00)97181-8,1990-01-01,0.583075610298245
Tetrahedron,Novel one step synthesis of epoxides from β-hydroxy-selenides and sulfides,,10.1016/s0040-4039(01)81495-7,1984-01-01,0.583072381950743
Tetrahedron,Synthesis of spiroketal fragment of ossamycin via Prins cyclization,,10.1016/j.tetlet.2014.11.097,2014-11-29,0.5830709867195435
Angewandte Chemie International Edition,Total Synthesis and Activity of the Metallo‐β‐lactamase Inhibitor Aspergillomarasmine A,"Resistance to β-lactam antibiotics is mediated primarily by enzymes that hydrolytically inactivate the drugs by one of two mechanisms: serine nucleophilic attack or metal-dependent activation of a water molecule. Serine β-lactamases are countered in the clinic by several codrugs that inhibit these enzymes, thereby rescuing antibiotic action. There are no equivalent inhibitors of metallo-β-lactamases in clinical use, but the fungal secondary metabolite aspergillomarasmine A has recently been identified as a potential candidate for such a codrug. Herein we report the synthesis of aspergillomarasmine A. The synthesis enabled confirmation of the stereochemical configuration of the compound and offers a route for the synthesis of derivatives in the future.",10.1002/anie.201510057,2015-12-28,0.5830695492934603
Journal of the American Chemical Society,Regioselective Chemoenzymatic Synthesis of Ganglioside Disialyl Tetrasaccharide Epitopes,"A novel chemoenzymatic approach for the synthesis of disialyl tetrasaccharide epitopes found as the terminal oligosaccharides of GD1α, GT1aα, and GQ1bα is described. It relies on chemical manipulation of enzymatically generated trisaccharides as conformationally constrained acceptors for regioselective enzymatic α2-6-sialylation. This strategy provides a new route for easy access to disialyl tetrasaccharide epitopes and their derivatives.",10.1021/ja5000609,2014-03-20,0.583067917870041
Organic Letters,Modular Synthesis of a Semibuckminsterfullerene,"A convergent synthesis of dibenzochrysenes and diindenochrysenes that proceeds from difluorofluorenes and acetoxyenone 15 has been used to prepare 5,6,11,12-tetrabromosemibuckminsterfullerene ( 31 ). The synthesis is highly modular and is distinguished by proceeding through an unsymmetrical intermediate. Our work will enable the straightforward preparation of semibuckminsterfullerenes from diindenochrysenes that lack bilateral symmetry using common reagents and nonpyrolytic conditions.",10.1021/acs.orglett.2c01880,2022-07-12,0.5830658823458321
Journal of Organic Chemistry,Synthesis of Chiral Polyhydroxylated Benzimidazoles by a Tandem Radical Fragmentation/Cyclization Reaction: A Straight Avenue to Fused Aromatic-Carbohydrate Hybrids,"The synthesis of benzimidazole-fused iminosugars through a tandem β-fragmentation-intramolecular cyclization reaction is described. The use of the benzimidazole ring as the internal nucleophile and the use of phenyliodosophthalate (PhI(Phth)), a new metal-free and low toxic hypervalent iodine reagent, are the most remarkable novelties of this synthetic strategy. With this approach, we have demonstrated the usefulness of the fragmentation of anomeric alkoxyl radicals promoted by the PhI(Phth)/I 2 system for the preparation of new compounds with potential interest for both medicinal and synthetic chemists.",10.1021/acs.joc.8b01988,2018-12-27,0.5830622769171451
Organic Process Research & Development,Streamlined Synthesis of a Bicyclic Amine Moiety Using an Enzymatic Amidation and Identification of a Novel Solid Form,"We describe a series of improvements to the synthesis of a 3,8-diazabicyclo[3.2.1]octane derivative that result in a reduced step count and higher overall efficiency compared to previously published syntheses. Our method includes optimization and mechanistic understanding of a key diastereoselective cyclization to achieve a >95:5 diastereomeric ratio, as well as demonstration of a unique enzyme-catalyzed amidation reaction using hexamethyldisilazane as both an ammonia source and scavenger. Finally, we identify a novel cocrystal solid form of the target compound that provides improved purity and material properties. Demonstration of the new chemistry to prepare >100 kg of the target compound serves to illustrate the robustness of the new process.",10.1021/acs.oprd.1c00120,2021-05-27,0.5830549333435455
Journal of Organic Chemistry,Synthesis of Poly(amino)ester Dendrimers via Active Cyanomethyl Ester Intermediates,"A novel strategy for the synthesis of poly(amino)ester dendrimers was developed on the basis of active cyanomethyl ester intermediates and an iteration of four consecutive steps of deprotection, activation, transesterification, and scavenging.",10.1021/jo101739x,2010-11-17,0.5830514199154189
Journal of Organic Chemistry,"Synthesis of all stereoisomers of eudesm-11-en-4-ol. 2. Total synthesis of selin-11-en-4.alpha.-ol, intermedeol, neointermedeol, and paradisiol. First total synthesis of amiteol","The syntheses of (±)-selin-11-en-4α-ol (5), (±)-intermedeol (6), (±)-neointermedeol (7), (±)-amiteol (9), and the four remaining unnatural stereoisomers (±)-paradisiol (8), (±)-7-epi-amiteol (10), (±)-5-epi-neointermedeol (11), and (±)-5-epi-paradisiol (12) are described. In addition, the related (±)-evuncifer ether (25) has been prepared. The syntheses started from the octahydro-8-hydroxy-4a,8-dimethyl-2(1H)-naphthalenones 1-4. The reaction sequence employed for the synthesis of 5, 7, 9, and 12 involved Wittig reaction, oxidative hydroboration, oxidation, equilibration, and olefination. For the synthesis of 6, 8, 10, and 11 the interim equilibration step was omitted. The oxidative hydroboration was the key step in these syntheses.",10.1021/jo00026a012,1991-12-01,0.5830439847049945
Synthesis,Scalable Synthesis of Lissamine Rhodamine B Sulfonyl Chloride and Incorporation of Xanthene Derivatives onto Polymer Supports,A scalable synthetic route to lissamine rhodamine B sulfonyl chloride has been developed and a series of monomeric derivatives of this xanthene dye have been synthesized. Their subsequent incorporation into polymer supports has been accomplished and led to improved thermal stability for the conjugates as compared to the free dye.,10.1055/s-2008-1032172,2008-03-01,0.5830430477198291
Organic Process Research & Development,Design and Scale-Up of Diels–Alder Reactions for the Practical Synthesis of 5-Phenylbicyclo[2.2.2]oct-5-en-2-one,"Several synthetic pathways towards racemic 5-phenylbicyclo[2.2.2]oct-5-en-2-one 1 have been devised starting with a Diels–Alder reaction of (cyclohexa-1,5-dien-1-yloxy)trimethylsilane and α-acetoxyacrylonitrile, acrylonitrile, or α-chloroacrylonitrile. The first ‘fit-for-purpose’ route relied on α-acetoxyacrylonitrile as a dienophile and rapidly delivered kilogram amounts of 1 . Process safety data then triggered the development of a scalable Diels–Alder reaction using α-chloroacrylonitrile as the dienophile. This practical and volume-efficient route delivered 1 in a 44% yield in six chemical steps with two isolated intermediates. Notably, neither chromatography nor distillation was required for the multikilogram synthesis of 1 .",10.1021/op200139r,2011-06-27,0.5830403766848613
Angewandte Chemie International Edition,Symmetry‐Based Design for the Chemoenzymatic Synthesis of Oseltamivir (Tamiflu) from Ethyl Benzoate,"A short chemoenzymatic formal synthesis of oseltamivir from ethyl benzoate has been achieved. The key steps involve a toluene dioxygenase-mediated dihydroxylation, hetero-Diels-Alder cycloaddition, and generation of C4 acetamido functionality. The formal synthesis of oseltamivir is achieved in ten steps and incorporates a unique translocation of the olefin with concomitant elimination of the C2 hydroxy group (see scheme).",10.1002/anie.200901345,2009-05-07,0.5830349123199319
Journal of Organic Chemistry,Total Synthesis of Herbicidin C and Aureonuclemycin: Impasses and New Avenues,"The undecose nucleoside antibiotics herbicidin C and aureonuclemycin are biologically highly active and represent challenging targets for total synthesis. Herein, the gradual evolution of our synthetic strategy toward these natural products is described in detail. The initial route encompasses metalate addition chemistry but suffers from poor stereochemical control. In contrast, the ultimately successful strategy benefits from a variety of reagent-controlled stereoselective transformations, including a surprisingly facile and highly diastereoselective N-glycosylation process. The presented work also describes new building blocks that might find further application in carbohydrate chemistry.",10.1021/jo401706r,2013-09-27,0.5830239329641955
Tetrahedron,A novel short synthesis of norbisabolide,,10.1016/s0040-4039(02)00814-6,2002-06-01,0.583022289435204
Organic Letters,Stereocontrolled Total Synthesis of the Potent Anti-inflammatory and Pro-resolving Lipid Mediator Resolvin D3 and Its Aspirin-Triggered 17<i>R</i>-Epimer,"The first total synthesis of stereochemically pure resolvin D3 and aspirin-triggered resolvin D3 is reported. These enzymatic metabolites of docosahexaenoic acid (DHA) have potent anti-inflammatory and pro-resolving actions. The convergent synthetic strategy is based on enantiomerically pure starting materials, and it is highly stereocontrolled.",10.1021/ol400484u,2013-03-19,0.5830214265107387
Journal of Organic Chemistry,Enantioselective Synthesis of β-Arylamines via Chiral Phosphoric Acid-Catalyzed Asymmetric Reductive Amination,"A new method for the synthesis of chiral β-aryl amines via chiral phosphoric acid-catalyzed enantioselective reductive amination of benzyl methyl ketone derivatives with Hantzsch ester was developed. Various chiral β-aryl amines were obtained in high yields and with good to high enantioselectivities. This transformation is applicable to gram-scale reactions, and the catalyst loading can be reduced to 1 mol % without sacrificing any catalytic efficacy. Furthermore, the resulting β-aryl amine was successfully converted into a tetrahydroisoquinoline compound without any loss of enantioselectivity.",10.1021/acs.joc.5b00812,2015-05-22,0.5830199226114856
Organic Letters,Synthesis of Fluorenones from Benzaldehydes and Aryl Iodides: Dual C–H Functionalizations Using a Transient Directing Group,"The first synthesis of substituted fluorenones directly from benzaldehydes and aryl iodides via a Pd(II)-catalyzed C(sp 2 )–H functionalization cascade is reported. Featuring anthranilic acid as an inexpensive transient directing group, the process is compatible with a variety of benzaldehydes and aryl iodides. A three-step synthesis of the antiviral drug Tilorone was completed in an excellent overall yield (40%), demonstrating the utility of this method.",10.1021/acs.orglett.7b00161,2017-02-22,0.5830133390876613
Angewandte Chemie International Edition,One‐Pot Synthesis of Cyclopropane‐Fused Cyclic Amidines: An Oxidative Carbanion Cyclization,"Abstract A novel and efficient one‐pot method has been developed for the synthesis of cyclopropane‐fused bicyclic amidines on the basis of a CuBr 2 ‐mediated oxidative cyclization of carbanions. The usefulness of this unique multicomponent strategy has been demonstrated by the use of a wide variety of substrates to furnish novel cyclopropane‐containing amidines with a quaternary center in very good yields. This ketenimine‐based approach provides straightforward access to biologically active and pharmaceutically important 3‐azabicyclo[ n .1.0]alkane frameworks under mild conditions. The synthetic power of this methodology is exemplified in the concise synthesis of the pharmaceutically important antidepressant drug candidate GSK1360707 and key intermediates for the synthesis of amitifadine, bicifadine, and narlaprevir.",10.1002/anie.201708138,2017-10-30,0.5829976528841769
Angewandte Chemie International Edition,"Gram‐Scale Access to (3,11)‐Cyclotaxanes—Synthesis of 1‐Hydroxytaxuspine C","Herein, we present the semisynthesis of complex taxane diterpenoid 1-hydroxytaxuspine C. Starting from cheap and abundant 10-deacetylbaccatin III, a scalable and robust route was developed, enabling an unprecedented gram-scale access to the intricate (3,11)-cyclotaxane scaffold. In addition, this represents the first synthetic access to C1-hydroxylated cyclotaxanes. The natural product is synthesized in 17 steps, with the reactions being performed on decagram-scale up to an advanced intermediate, establishing the scalability of this approach.",10.1002/anie.202506245,2025-06-16,0.5829963989575365
Journal of Organic Chemistry,Concise and Stereocontrolled Synthesis of Pseudo-<i>C</i><sub>2</sub>-symmetric Diamino Alcohols and Triamines for Use in HIV Protease Inhibitors,"A new protocol is described for the stereocontrolled synthesis of pseudo-C(2)-symmetric core units of interest as candidates for HIV protease inhibition. Addition of unbranched and branched organolithium reagents to cyanohydrins from l-phenylalaninal and l-isoleucinal, followed by in situ reduction of the intermediate imines and CHT deprotection under MW irradiation, led to 1,3-diamino alcohols 6a and 8a as the major products in satisfactory to good yields. The first preparation of a previously unreported pseudo-C(2)-symmetric triamino derivative was accomplished expeditiously via high-yielding nitro-Mannich addition of the silylnitronate, from 2-phenyl-1-nitroethane, to the PMP imine derived from l-phenylalaninal. Reduction of the nitro group in the moderately unstable nitro diamine adduct, followed by chromatographic separation of the required diastereoisomer and CHT debenzylation under MW irradiation, led to the 2-PMP-protected triamine 19 isolated as a bis(sulfonamide).",10.1021/jo026616j,2003-01-22,0.5829954008441683
Tetrahedron,"Hydrogenation of 1-benzyl-3-(2,2-dimethyl-1,3-dioxolan-4-yl)-aziridine-2-carboxylic acid ethyl ester",,10.1016/s0040-4039(00)78356-0,1994-10-01,0.5829937672661746
Organic Letters,Co(acac)<sub>2</sub>/O<sub>2</sub>-Mediated Oxidative Isocyanide Insertion with 2-Aryl Anilines: Efficient Synthesis of 6-Amino Phenanthridine Derivatives,A novel and efficient protocol for the creation of 6-amino phenanthridine derivatives by Co(acac)2-catalyzed isocyanide insertion with 2-aryl anilines under an O2 atmosphere via homolytic aromatic substitution (HAS) type C-H functionalization has been developed. This reaction not only proceeds smoothly utilizing O2 as the oxidant but also provides a new approach to construct phenanthridine derivatives utilizing readily available 2-aryl anilines with isocyanides instead of 2-isocyanobiaryls with different radical precursors.,10.1021/ol500286x,2014-02-07,0.5829920819972544
Organic Letters,"Asymmetric Synthesis of Spiroketal, Spiroether, and Oxabicycle Building Blocks via Stereoselective Spiro- and Bicycloannulation of 2-Hydroxy Dihydropyrans","A modular asymmetric synthesis of spiroketal, spiroether, and oxabicycle building blocks is described based on the spiro- and bicycloannulation of alpha-hydroxy dihydropyrans, which were obtained from sulfoximine-substituted homoallylic alcohols. Key steps of the syntheses are stereoselective Ferrier-type O- and C-glycosidation, ring-closing metathesis, and stereoselective Prins cyclization.",10.1021/ol800854s,2008-05-31,0.5829736499276795
Journal of Organic Chemistry,Copper-Catalyzed Coupling between <i>ortho</i>-Haloanilines and Lactams/Amides: Synthesis of Benzimidazoles and Telmisartan,"An efficient copper-catalyzed synthesis of (annelated) benzimidazoles is reported. This transformation is based on a simple and straightforward one-pot sequence involving a copper-catalyzed cross coupling between o -haloanilines and lactams/amides followed by a subsequent cyclization under acidic conditions. A variety of (annelated) benzimidazoles could be easily obtained in high yields from readily available starting materials, and this procedure could be further applied to the synthesis of the antihypertensive blockbuster drug telmisartan.",10.1021/acs.joc.3c02905,2024-04-02,0.5829708344527806
Journal of Organic Chemistry,A Formal Synthesis of (−)-Cyanolide A Featuring a Stereoselective Mukaiyama Aldol Reaction and Oxocarbenium Reduction,"The formal synthesis of the marine natural product (-)-cyanolide A is presented. The synthetic strategy is centered on two acyclic diastereoselective reactions and a single cyclic reaction with modest to excellent dr based on an initial stereocenter. Most notable is a highly stereoselective oxocarbenium reduction based on a ""mismatched"" reactive conformer to afford the β-C-glycoside subunit leading to an efficient synthesis of the diolide aglycon in 12 overall steps.",10.1021/jo201210u,2011-08-25,0.5829686981072923
Tetrahedron,"Synthesis and photolysis behaviour of 2-(Δ1-pyrazolinyl)-Δ3(1,3,4) oxadiazolines. Application to the synthesis of gem-dimethylcyclopropane ketone",,10.1016/s0040-4039(99)01920-6,1999-12-01,0.5829660686990911
Tetrahedron,A concise synthesis of the HIV-protease inhibitor nelfinavir via an unusual tetrahydrofuran rearrangement,,10.1016/s0040-4039(00)01231-4,2000-09-01,0.5829660189183893
Organic Letters,A Pauson−Khand and Ring-Expansion Approach to the Aquariane Ring System,"[Structure: see text] The carbocyclic ring system of the aquariolide diterpenes has been synthesized by two routes involving a diastereoselective Pauson-Khand reaction and subsequent ring expansion. In one route, a tetracyclic enone was elaborated to generate the nine-membered ring by Grob fragmentation. In the second approach, a spirocyclic tricycle underwent a facile anionic oxy-Cope rearrangement to complete the synthesis of the desired ring system.",10.1021/ol0609715,2006-06-20,0.5829649377009777
Angewandte Chemie International Edition,Stereocontrolled Total Synthesis of (+)‐Leucascandrolide A,"Apparently no longer available from its natural source is the potent cytotoxic and antifungal agent leucascandrolide A (1), which was initially isolated from a New Caledonian calcareous sponge. A highly stereocontrolled total synthesis of this structurally unique macrolide commences with a Jacobsen asymmetric hetero Diels–Alder reaction to configure the tetrahydropyran ring. An efficient endgame relies on two Mitsunobu reactions, the first to generate the 18-membered macrolactone and the second to attach the oxazole-bearing side chain.",10.1002/anie.200390112,2003-01-20,0.5829643631990861
Tetrahedron,"Synthesis of the highly potent prostanoid FP receptor agonist, AFP-168: a novel 15-deoxy-15,15-difluoroprostaglandin F 2α derivative",,10.1016/j.tetlet.2003.12.029,2004-01-15,0.582959956081435
Angewandte Chemie International Edition,"Rhodium‐Catalyzed Regio‐ and Enantioselective Intermolecular [4+2] Carbocyclization of 4‐Alkynals with <i>N</i>,<i>N</i>‐Dialkyl Acrylamides","Selective rings: A cationic RhI–(R,R)-walphos complex catalyzes a highly regio- and enantioselective intermolecular [4+2] carbocyclization of 4-alkynals with N,N-dialkyl acrylamides to afford enantioenriched cyclohexanones (see scheme; cod=cycloocta-1,5-diene). This new route is attractive in view of the one-step access to 4-alkynals from commercially available reagents.",10.1002/anie.200502380,2005-10-18,0.5829534778742848
Organic Process Research & Development,"Development of an Optimized Synthetic and Purification Process of S-2367 (Velneperit), a Novel Neuropeptide Y (NPY) Y5 Receptor Antagonist","We developed a simple synthetic route to S-2367 (Velneperit) ( 1 ) using trans -1-ethoxycarbonyl-4-aminocyclohexane hydrochloride salt ( 12 ) as a starting material. The key step was Na 2 WO 4 /H 2 O 2 oxidation, and we found that it was accelerated in weakly basic conditions. The finding was useful to control one of the critical impurities: 14 in 10 . The new process was more efficient than the early process from the viewpoint of the number of reactions, yield, throughput, and EHS (environment, health, and safety) but a quality deviation occurred in the pilot manufacturing: 10 content in 1 was over the upper limit. The cause was presumed to be hydrolysis of 1 during the recrystallization step. After finding it, we developed two reliable purification processes. The first was slurry washing including clever polymorphic control using only acetone and water. The second was salt formation of 10 and rational building of the recrystallization procedure based on solubility to improve removal rate.",10.1021/acs.oprd.5b00023,2015-03-25,0.5829515612701037
Synthesis,Asymmetric Synthesis via Heterocyclic Intermediates; XXXVII<sup>1</sup>Asymmetric Synthesis of Dimethyl (R)-2-Amino-(<i>E</i>)-hept-4-enedioates by the Bislactim Ether Method,"All articles of this category An asymmetric synthesis of (virtually enantiomerically and diasteriomerically pure) dimethyl (2 R , 3?)-2-amino-( E )-heptene-1,7-dioates of type 9 is described.",10.1055/s-1988-27504,1988-01-01,0.5829514071952666
Tetrahedron,A convenient route to aryl substituted chloro and bromo olefins,,10.1016/s0040-4039(97)00277-3,1997-03-01,0.5829509731043653
Organic Letters,Catalytic Enantioselective Synthesis of Naturally Occurring Butenolides via <i>Hetero</i>-Allylic Alkylation and Ring Closing Metathesis,"An efficient catalytic asymmetric synthesis of chiral γ-butenolides was developed based on the hetero-allylic asymmetric alkylation (h-AAA) in combination with ring closing metathesis (RCM). The synthetic potential of the h-AAA-RCM protocol was illustrated with the facile synthesis of (-)-whiskey lactone, (-)-cognac lactone, (-)-nephrosteranic acid, and (-)-roccellaric acid.",10.1021/ol102994q,2011-01-26,0.5829501868211732
Organic Process Research & Development,"Evaluation of Novel Synthetic Methods for the Preparation of the Sodium Channel Inhibitor, GW273225X","The evaluation of efficient synthetic methods for the preparation of ( R )-2,4-diamino-5-(2,3-dichlorophenyl)-6-fluoromethylpyrimidine, GW273225X ( 1 ), is described. The initial synthesis using ethylfluoroacetate was evaluated against three alternative routes using either nucleophilic fluorination, electrophilic fluorination, or sodium fluoroacetate.",10.1021/op4001753,2013-11-18,0.5829496988558167
Synthesis,Stereoselective Total Syntheses of Leiocarpin A and (-)-Galantinic Acid Starting from d-Mannitol,"Stereoselective total syntheses of leiocarpin A and (-)-galantinic acid, starting from d-mannitol as a chiral synthon, are described. The key steps involve stereoselective allylations, a Grignard reaction to control the required stereogenic centers, and ring-closing metathesis followed by intramolecular Michael addition.",10.1055/s-0028-1087993,2009-03-06,0.5829384161889616
Synthesis,Synthesis of Ferrocenyloxazolines Incorporating Secondary Functionalities,"All articles of this category The synthesis of novel ferrocenyloxazolines incorporating secondary ester, bromo and hydroxy functionalities either on the oxazoline unit or the other cyclopentadiene ring of the ferrocene core has been achieved. The X-ray structure of a homochiral ferrocenyloxazoline derivative 11 incorporating a tertiary alcohol side chain appended to the oxazoline ring is reported. ferrocene - chiral oxazoline - amino alcohol - crystal structure",10.1055/s-1998-2051,1998-04-01,0.5829361258216021
Synthesis,Organometallic NucleosideAnalogues: An Adenine-Analogue Fischer Carbene Complex,"A six-step synthesis of a nucleoside analogue Fischer carbenecomplex has been developed starting from d-ribono-1,4-lactone.The key steps involve a stoichiometric metathesis of exo-glycal 3 withpentacarbonyl[(diphenyl)carbene]chromium to give chromiumfuranosylidene 4, its ring-opening aminolysiswith the nucleobase adenine and a Mitsunobu recyclisation leadingto imino-l-lyxo-furanosylidene complex 6 with inversion of configuration.",10.1055/s-2003-41032,2003-01-01,0.5829258648717761
Organic Letters,Five-Step Total Synthesis of (±)-Aspidospermidine by a Lactam Strategy via an Azomethine Ylide,A five-step total synthesis of (±)-aspidospermidine ( 1 ) based on a lactam strategy is reported. Our synthesis features an iridium-catalyzed reductive Michael addition/[3+2] cycloaddition cascade to give a tricyclic ketone intermediate from a simple lactam via an azomethine ylide. The developed strategy enables easily available lactams to be used as stable surrogates of multisubstituted amines and would be applicable to a unified total synthesis of complex Aspidosperma alkaloids.,10.1021/acs.orglett.1c00735,2021-04-06,0.582925093862869
Organic Letters,"Isolation, Structure Determination, and Synthesis of Neodysiherbaine A, a New Excitatory Amino Acid from a Marine Sponge","[structure: see text] A new excitatory amino acid, neodysiherbaine A (2), was isolated as a minor constituent of the aqueous extract from the marine sponge Dysidea herbacea. The structure was deduced by spectroscopic methods and established unambiguously by the total synthesis. The present synthesis, including as a key step cross-coupling of the 6/5-bicyclic core with an amino acid residue, is useful in constructing its structural analogues.",10.1021/ol015798l,2001-04-14,0.5829238886828552
Journal of Organic Chemistry,Asymmetric Synthesis of Enantioenriched 6-Hydroxyl Butyrolactams Promoted by N-Heterocyclic Carbene,"Herein, an efficient route to synthesize 6-hydroxyl butyrolactams has been successfully developed via an N-heterocyclic carbene-catalyzed formal [3 + 2] annulation of bromoenals with α-amino ketones, followed by reduction. Remarkably, enantioenriched epi -neoclausenamide, which is one of the clausenamide derivatives, could be efficiently prepared by this strategy.",10.1021/acs.joc.9b01490,2019-07-22,0.5829139836773638
Synlett,The Untold Journey of Total Synthesis of Natural Products,"Abstract This personal Account presents the developments of two synthetic strategies (Phenol Oxidative Dearomatization, POD; and Furan Oxidative dearomatization, FOD) for total synthesis of natural products. The POD program was originally derived from our first total synthesis of tenuipyrone, while our productive FOD program arose from the total synthesis of the uprolide family. Instead of a review summary of our total synthesis, this Account is focused on how these total synthesis projects are conceived and connected from the perspective of laboratory development. It is evident that total synthesis is not an isolated event, but a connecting and inspirational point that sparks new ideas and new projects. 1 Introduction 2 Total Synthesis versus Synthetic Methodology 3 Development of Phenol Oxidative Dearomatization (POD) for Total Synthesis 4 Development of Furan Oxidative Dearomatization (FOD, Achmatowicz rearrangement) for Total Synthesis 5 Conclusion and Outlook",10.1055/a-2010-7874,2023-01-11,0.5829090863954427
Synlett,"N,N-Dibenzylaminoacetonitrile, a Highly Efficient Synthon for the Synthesis of (±)-cis- and (±)-trans-2,3-Methanohomoserines",,10.1055/s-1991-20863,1991-01-01,0.5829063889100121
Journal of Organic Chemistry,Expedient Stereoselective Synthesis of Coronafacic Acid Through Intramolecular Diels−Alder Cyclization,"A stereoselective synthesis of coronafacic acid, a natural component of the phytotoxin coronatin, was achieved using an intramolecular Diels-Alder reaction as the key step. The triene precursor bearing a substituted diene and a vinylketone as dienophile was synthesized and then tested in the thermal intramolecular cyclization. We have devised a new strategy to assemble the E,Z-diene through the stereoselective aldol reaction of an ester enolate followed by a stereoselective dehydration. Following the thermal cyclization, the corresponding hydrindanone thereby obtained with the desired relative stereochemistry could easily be converted into the natural product. The synthesis of the coronafacic acid was accomplished in six steps in 29% overall yield.",10.1021/jo062099j,2007-01-26,0.5829050743978051
Angewandte Chemie International Edition,Enantioselective Synthesis of Axially Chiral Benzothiophene/Benzofuran‐Fused Biaryls by N‐Heterocyclic Carbene Catalyzed Arene Formation,"Axially chiral biaryl scaffolds are prevalent in natural products, chiral ligands, and organocatalysts. However, N-heterocyclic carbene (NHC) catalyzed de novo construction of an aromatic ring with concomitant axial chirality induction for the synthesis of biaryl atropisomers is far less developed, and the efficient synthesis of axially chiral tetra-ortho-substituted biaryls remains an unsolved problem under NHC catalysis. Reported here is an NHC-catalyzed de novo synthesis of axially chiral benzothiophene/benzofuran-fused biaryls from enals and 2-benzyl-benzothiophene/benzofuran-3-carbaldehydes through a [2+4] annulation, decarboxylation, and oxidative aromatization cascade with central-to-axial chirality conversion. The developed method provides efficient and general access to novel axially chiral benzothiophene/benzofuran-fused biaryls in high enantioselectivities and works well for the synthesis of tetra-ortho-substituted biaryls.",10.1002/anie.202103415,2021-04-14,0.582901719192988
Journal of Organic Chemistry,"Total Synthesis of the Pseudopterane (−)-Kallolide B, the Enantiomer of Natural (+)-Kallolide B","A total synthesis of the enantiomer 35 of kallolide B was achieved starting from (S) -(−)-perillyl alcohol ( 8 ). Oxidative cleavage to the ester aldehyde 11 was effected by treatment of the epoxide 9 with H 5 IO 6 followed by CH 2 N 2 . The allenyl ketone 13, obtained by SnCl 2 -promoted addition of 1-bromo-2-butyne to aldehyde 11 and subsequent Swern oxidation, cyclized to the furan 14 in the presence of catalytic AgNO 3 . Homologation of the derived aldehyde 15 with CBr 4 −Ph 3 P followed by n -BuLi and CH 2 O led to the propargylic alcohol 17 . Formylation of the furan 17 ( s -BuLi, DMF) and then Still−Horner−Emmons homologation yielded the (Z) -conjugated ester 22 . Conversion of the propargylic alcohol function to the chloride 23 and ester reduction (DIBAL-H) furnished the chloro alcohol 24, which formed the cyclic ether 25 upon treatment with NaH. Ether 25 underwent a highly diastereoselective [2,3]Wittig ring contraction to the propargylic alcohol 26 . The derived mesylate 36 was converted to the allenic ester 37 with CO and TMSCH 2 CH 2 OH in the presence of Pd(PPh 3 ) 4 . Ester 37 was isomerized to the diastereomer 39 with Ph 3 P in CH 3 CN. Ester cleavage with TBAF followed by cyclization of the acid intermediate with catalytic AgNO 3 led to butenolide 35, identical to kallolide B according to comparison of NMR spectra, but of opposite optical rotation.",10.1021/jo960798y,1996-01-01,0.582899214374229
Synthesis,Synthese von Bryophyten-Inhaltstoffen 1. Neue Synthesen der Lunularsäure und einiger ihrer Derivate,All articles of this category New Syntheses of Lunularic Acid and Some of Its Derivatives Efficient and convenient procedures are reported for the synthesis of lunularic acid ( 2 ) and for some of its derivatives on a preparative scale starting from the methyl ether 5 or the acetate 12 of ethyl 6-methylsalicylate ( 4 ) and introducing the bibenzyl moiety by metalation/ alkylation or by bromination / Wittig reaction/ hydrogenation sequences.,10.1055/s-1988-27624,1988-01-01,0.5828944209142629
Tetrahedron,Synthesis of a novel class of chiral polyaromatic amide dendrimers bearing an amino acid derived C3-symmetric core,,10.1016/s0040-4039(02)02518-2,2003-01-01,0.5828919003788889
Synlett,"Construction of the (1α,5α,6α)-6-Amino-3-azabicyclo[3.1.0]hexane Ring System","All articles of this category The use of bromonitromethane in the synthesis of the (1α,5α,6α)-6-amino-3-azabicyclo[3.1.0]hexane ring system is described. Bromonitromethane - three-ring annulation - 6-amino-3-azabicyclo[3.1.0]hexane - maleimide - diamine",10.1055/s-1996-5683,2000-12-31,0.5828909449677534
Organic Letters,Synthesis of Unsymmetrical <i>o</i>-Biphenols and <i>o</i>-Binaphthols via Silicon-Tethered Pd-Catalyzed C−H Arylation,"A mild, practical, and efficient method for the synthesis of unsymmetrical o-biphenols (including o-phenol-naphthols and o-binaphthols) has been developed. Unsymmetrical bis-aryloxy silanes, which were readily prepared in a semi-one-pot fashion, underwent the Pd-catalyzed intramolecular arylation followed by a routine TBAF desilylation step to furnish valuable unsymmetrical biphenols without necessity of isolation of seven-membered intermediates. The excellent functional group tolerance allows for synthesis of a variety of functionalized o-biphenols and o-binaphthols from easily available staring materials.",10.1021/ol100924n,2010-04-27,0.5828873684103965
Journal of Organic Chemistry,"Total Syntheses of (−)-α-Kainic Acid and (+)-α-Allokainic Acid via Stereoselective C−H Insertion and Efficient 3,4-Stereocontrol.","Reported herein is a novel approach to the total syntheses of (−)-α-kainic acid and (+)-α-allokainic\nacid, where the stereochemistries on C(2), C(3), and C(4) of the pyrrolidine core were introduced efficiently\nand selectively. A regio- and stereoselective C−H insertion reaction was utilized to prepare the γ-lactam\nas an intermediate. A Michael-type cyclization of phenylsulfone with a conjugated acetylenic ketone\nwas developed to prepare the tricyclic ketone as a key intermediate for (−)-α-kainic acid. Subsequently,\na stereoselective dephenylsulfonylation was carried out successfully to secure the cis relationship at C(3)\nand C(4) centers. An unprecedented acetylation on the phenylsulfone, followed by a stereoselective\ndephenylsulfonylation, secured the trans relationship at C(3) and C(4) centers in (+)-α-allokainic acid.",10.1021/jo800288p,2008-02-15,0.5828836357734674
Synlett,A Short-Step Asymmetric Synthesis of Dehydrodiconiferyl Alcohol via C-H Insertion Reaction,"A rhodium-catalyzed intramolecular C-H insertion reaction using a chiral auxiliary and a chiral catalyst was employed to achieve double asymmetric induction of a trans-disubstituted dihydrobenzofuran ring, as the key reaction of a stereoselective synthesis of (-)-dehydrodiconiferyl alcohol in 13 steps from commercially available guaiacol.",10.1055/s-0031-1290658,2012-03-28,0.5828758018818544
Tetrahedron,"A simple, two-step synthesis of 3-iodoindoles",,10.1016/j.tetlet.2003.10.207,2003-12-04,0.5828750150190163
Synthesis,"A Simple, One-Step Synthesis of Benzo- and Dibenzofluorenones",,10.1055/s-1974-23317,1974-01-01,0.5828750150190163
Synthesis,2-Aroylimidazoles; A Simple One-Step Synthesis,,10.1055/s-1978-24848,1978-01-01,0.5828750150190163
Angewandte Chemie International Edition,Total Synthesis of (+)‐Dactylolide through an Efficient Sequential Peterson Olefination and Prins Cyclization Reaction,"Key steps in the total synthesis of the macrolide natural product (+)-dactylolide (see formula) include two enantioselective vinylogous Mukaiyama reactions, fragment coupling through acetal formation, a sequential Peterson olefination/Prins cyclization reaction that proceeds under very mild conditions, and a Mislow–Evans rearrangement to effect the transposition of an allylic alcohol.",10.1002/anie.200500564,2005-04-21,0.5828741596441097
European Journal of Organic Chemistry,Synthetic Studies towards Pheromones by Cyanide‐Catalyzed Ring Transformation of α‐Hydroxy‐β‐oxoesters to δ‐Valerolactones,"Abstract The cyanide‐catalyzed ring‐transformation of α‐hydroxy‐β‐oxoesters to δ‐lactones with exocyclic ester moiety is the key transformation for the preparation of racemic 5‐hexadecanolide (15 % over nine steps) and 6‐acetoxy‐5‐hexadecanolide (22 % over eight steps), two insect pheromones. The benzyloxycarbonyl moiety is transformed via the acid chloride to the undecanoyl side chain. After reduction of the ketone to the secondary alcohol, this functional group was either reduced via the chloro compound to furnish the 5‐hexadecanolide. On the other hand, stereoselective reduction of the ketone gave secondary alcohol with the wrong relative configuration, which was established by X‐ray single‐crystal structure. Inversion was achieved by reaction of the methanesulfonate with cesium acetate yielding ( R *, S *)‐6‐acetoxy‐5‐hexadecanolide with the relative configuration also present in the natural product.",10.1002/ejoc.202201391,2022-12-21,0.5828734825514492
Tetrahedron,"Sequosempervirin A, a novel spirocyclic compound from Sequoia sempervirens",,10.1016/j.tetlet.2004.04.038,2004-05-01,0.5828710714954476
Tetrahedron,"Unedoside, a novel iridoid compound",,10.1016/s0040-4039(01)99702-3,1966-01-01,0.5828710714954476
Tetrahedron,"Heterophylol, a phenolic compound with novel skeleton from Artocarpus heterophyllus",,10.1016/s0040-4039(00)61402-8,1993-12-01,0.5828710714954476
Tetrahedron,"Pukeleimide C, a novel pyrrolic compound from the marine cyanophyte",,10.1016/s0040-4039(01)86248-1,1979-01-01,0.5828710714954476
Organic Process Research & Development,Process Development and Pilot-Plant Synthesis of (2-Chlorophenyl)[2-(phenylsulfonyl)pyridin-3-yl]methanone,"Routes to (2-chlorophenyl)[2-(phenylsulfonyl)pyridin-3-yl]methanone, 1, an intermediate in the manufacture of NK1-II inhibitor LY686017 are described which produce 1 in >75% yield and 95% purity. A highly selective telescoped ortho lithation/condensation/oxidation process was developed and successfully scaled to the clinical pilot plant to produce 25 kg of 1 . For the pilot-plant campaign, the lithiation step was developed to operate at −50 °C using commercial lithium diisopropylamide (LDA), and the oxidation step employed catalytic TEMPO as the primary and NaOCl as the terminal oxidant. After completion of the pilot-plant campaign second-generation approaches to 1 were developed to improve process greenness where the lithiation and condensation step were operated as warm as −10 °C, the highly efficient AZADO catalyst was used as a substitute for TEMPO in the Anelli−Montanari oxidation, and process mass intensity was reduced 25%.",10.1021/op100157q,2010-08-31,0.5828676995737265
European Journal of Organic Chemistry,"Absolute Stereochemical Assignment and Fluorescence Tuning of the Small Molecule Tool, (–)‐Blebbistatin","Abstract (–)‐Blebbistatin ( 1 ), a recently discovered small molecule inhibitor of the ATPase activity of non‐muscle myosin II has been prepared from methyl 5‐methylanthranilate ( 6 ) in three steps. This flexible synthetic route has also been used to prepare a nitro group‐containing analogue 12 that has modified fluorescence properties and improved stability under microscope illumination. The key step in the synthesis of 1 and its analogues was the asymmetric hydroxylation of the quinolone intermediate 3 using the Davis oxaziridine methodology. The absolute stereochemistry of (–)‐blebbistatin ( 1 ) was shown to be S by X‐ray crystal structure analysis of a heavy atom (bromine) containing analogue 11 , which was subsequently reduced and shown to be identical to 1 . (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2005)",10.1002/ejoc.200500103,2005-04-25,0.5828593353738535
European Journal of Organic Chemistry,Stereodivergent Synthesis of Hetero-Fused Isoquinolines by Acyliminium and Metallation Methods,"Diastereodivergent syntheses of 1,10b-cis- and 1,10b-trans-thiazolo[4,3-a]isoquinoline systems are reported. The key transformations are based on the intramolecular cyclization of aryllithiums and N-acyliminium ions. With 5-substituted N-phenethylthiazolidinediones as substrates, hydride reduction or the organolithium addition−N-acyliminium cyclization sequence stereoselectively afforded the 1,10b-cis derivatives. Alternatively, the tandem Parham cyclization−hydroxyl reduction using the corresponding iodinated thiazolidinediones occurred with complete control of stereoselectivity, producing the 1,10b-trans diastereomers. Although it was not possible to synthesise imidazo[4,3-a]isoquinolinones by N-acyliminium cyclizations, application of the Parham cyclization−reduction sequence to N-phenethylhydantoins constituted an efficient alternative for the synthesis of these hetero-fused isoquinolines with 1,10b-trans stereochemistry. Ready access to 1-phenethylisoquinolines is also described.",10.1002/1099-0690(200104)2001:7<1267::aid-ejoc1267>3.0.co;2-n,2001-04-01,0.5828548298867657
European Journal of Organic Chemistry,Stereodivergent Synthesis of Hetero-Fused Isoquinolines by Acyliminium and Metallation Methods,"Diastereodivergent syntheses of 1,10b-cis- and 1,10b-trans-thiazolo[4,3-a]isoquinoline systems are reported. The key transformations are based on the intramolecular cyclization of aryllithiums and N-acyliminium ions. With 5-substituted N-phenethylthiazolidinediones as substrates, hydride reduction or the organolithium addition−N-acyliminium cyclization sequence stereoselectively afforded the 1,10b-cis derivatives. Alternatively, the tandem Parham cyclization−hydroxyl reduction using the corresponding iodinated thiazolidinediones occurred with complete control of stereoselectivity, producing the 1,10b-trans diastereomers. Although it was not possible to synthesise imidazo[4,3-a]isoquinolinones by N-acyliminium cyclizations, application of the Parham cyclization−reduction sequence to N-phenethylhydantoins constituted an efficient alternative for the synthesis of these hetero-fused isoquinolines with 1,10b-trans stereochemistry. Ready access to 1-phenethylisoquinolines is also described.",10.1002/1099-0690(200104)2001:7<1267::aid-ejoc1267>3.3.co;2-e,2001-04-01,0.5828548298867657
Tetrahedron,"Efficient synthesis of zealexin B1, a maize sesquiterpenoid phytoalexin, viaSuzuki-Miyaura coupling",,10.1016/j.tetlet.2022.153641,2022-01-17,0.5828522007159312
Tetrahedron,Photocatalytic aerobic oxidation/semipinacol rearrangement sequence: a concise route to the core of pseudoindoxyl alkaloids,,10.1016/j.tetlet.2014.06.102,2014-07-02,0.5828507022080215
Tetrahedron,A simple and efficient synthesis of benzofuroquinolines via the decarboxylative cross-coupling,,10.1016/j.tetlet.2020.152808,2021-01-13,0.5828477694854364
Journal of Organic Chemistry,A Formal Total Synthesis of the Salicylihalamides,The synthesis of the macrolactone 23 is described. The synthesis features a diastereoselective hydroboration of the chiral alkene 17 followed by a Suzuki cross-coupling reaction with the benzoate 5. The resulting seco acid 21 was converted to the macrolactone 23 by a Mitsunobu lactonization using immobilized triphenylphosphine. The stereogenic centers in the alkene 17 were established by a Noyori reduction of the beta-keto ester 8 and an Evans aldol reaction. The synthesis illustrates the conversion of a syn aldol product to the corresponding anti product by inversion of the methyl-bearing center.,10.1021/jo035054g,2003-09-23,0.5828472220607642
Tetrahedron,New route to protoporphyrins III and XIII from common starting pyrroles,,10.1016/s0040-4039(02)00466-5,2002-04-01,0.5828459342346193
Journal of Organic Chemistry,Exploring the Chemistry of Epoxy Amides for the Synthesis of the 2′′-<i>epi</i>-Diazepanone Core of Liposidomycins and Caprazamycins,"New synthetic strategies have been explored for the synthesis of the structural core of liposidomycins and caprazamycins, an intriguing class of complex nucleoside-type antibiotics. This structural core is comprised of a cyclic diazepanone system linked to an uridyl fragment. The various synthetic approaches have in common that they originate from an epoxy amide derived from uridine, obtained via reaction of uridyl aldehyde 19 with an amide-stabilized sulfur ylide. Two different strategies were shown to be efficient in constructing the diazepanone ring system: (a) a reductive amination of an epoxy aldehyde with N-methylamine with subsequent intramolecular oxirane ring opening and (b) a carbene insertion reaction of an acyclic diazoamine precursor.",10.1021/jo202061t,2012-01-09,0.5828431272015622
Organic Process Research & Development,Practical Nonazide Synthesis of a <scp>d</scp>-Amino Acid Oxidase Inhibitor via a Sequential Erlenmeyer–Plöchl Reaction and Ligand-Free Copper(I) Amination Protocol,"A synthetic route to fused heterocycle 5 (R 1 = Et) was developed that avoids the use of troublesome azido functionality. In this approach, 3-bromofuran aldehyde 7 was synthesized from 3-bromofuran 6 using highly regioselective formylation conditions. The crude solution of 7 was treated with hippuric acid under Erlenmeyer–Plöchl conditions to give enamide product 16, which was isolated by crystallization. Intramolecular amination/cyclization to the fused pyrrole was achieved under ligand-free Cu(I) catalysis in toluene, followed by diamine workup to remove the benzoyl protecting group and residual copper. The final product 5 (R 1 = Et) was crystallized directly from the reaction mixture, providing up to 60% overall yield over five chemical steps and two isolations.",10.1021/op4001737,2013-08-27,0.5828377143825942
Tetrahedron,A new synthesis of phosphasteroids employing the McCormack cycloaddition for construction of the D-ring,,10.1016/s0040-4039(01)92630-9,1977-01-01,0.5828350098060848
Organic Letters,"New Stereodivergent Approach to 3-Amino-2,3,6-trideoxysugars. Enantioselective Synthesis of Daunosamine, Ristosamine, Acosamine, and Epi-daunosamine","[reaction: see text] An enantioselective preparation of the four diastereomeric 3-amino-2,3,6-trideoxy-hexoses, key components of anthracycline antibiotics, has been developed. Sharpless catalytic asymmetric epoxidation of the (2E)-2,5-hexadien-1-ol, regioselective ring opening with azide, followed by convenient functional group transformations, afforded the key aldehydes cis- or trans-6 in any configuration. The diastereoselective addition of methylmetal reagents to these aldehydes followed by ozonolysis gives access in a completely stereocontrolled manner to the four isomeric trideoxyaminosugars.",10.1021/ol034843h,2003-07-19,0.582830737879316
Tetrahedron,"A convenient new route to protected and free 2,6-anhydro-d-glycero-d-gulo-heptoses (1-formyl-β-d-glucopyranosides)",,10.1016/j.tetlet.2004.08.034,2004-09-14,0.5828286463096116
Journal of the American Chemical Society,Macrolactonization via Ti(IV)-Mediated Epoxy-Acid Coupling:  A Total Synthesis of (−)-Dactylolide [and Zampanolide],"A total synthesis of dactylolide (1) is described. The key feature involves the Ti(IV)-mediated coupling of structurally complex ""Sharpless epoxides"" and carboxylic acids in either an intramolecular (macrolactonization) or an intermolecular mode. Other notable aspects include a proton-catalyzed, cis-selective construction of the 4-methylenetetrahydropyran ring; a selective oxidation of an allylic alcohol in the presence of a 1,2-diol by an oxoammonium ion; an efficient ring-closing metathesis reaction of an in situ (bis-TMS) protected alpha,omega-diene-vic-diol; and an aluminum-mediated aza-aldol reaction of a primary amide to 1 to construct the acyclic carbinolamide in zampanolide.",10.1021/ja035579q,2003-07-17,0.5828262367951882
Synlett,First Synthesis of (+)-Pteroenone: A Defensive Metabolite of the Abducted Antarctic Pteropod<i>Clione antarctica</i>,"(+)-Pteroenone, a defensive metabolite of the abducted antarctic pteropod Clione antarctica, was firstly and efficiently synthesized by employing anti-selective aldol reaction as the key step.",10.1055/s-2005-862389,2005-01-01,0.5828251734727751
Organic Letters,"A Novel One-Pot Approach of Hexahydropyrrolo[2,3-<i>b</i>]indole Nucleus by a cascade addition/cyclization strategy: Synthesis of (±)-Esermethole","A practical and efficient synthesis of 3-substituted hexahydropyrrolo[2,3-b]indole is described. The addition/cyclization of 3-substituted indoles with alpha,beta-dehydroamino esters in the presence of a Lewis acid provides hexahydropyrrolo[2,3-b]indole adducts in good yields and stereoselectivities. This approach has been applied to the concise synthesis of esermethole employing an appropriately substituted indole and an N-acyl dehydroamino ester.",10.1021/ol101527j,2010-08-12,0.5828237178375122
Journal of Organic Chemistry,A Short Route to Enantiomerically Pure Benzophenanthridinone Skeleton:  Synthesis of Lactone Analogues of Narciclasine and Lycoricidine,"Condensation of functionalized o-toluamide anions on a carbohydrate-derived lactone, followed by intramolecular aldol cyclization, provides enantiomerically pure 2-arylcyclohexenones. Different approaches for the stereoselective transformation of the carbonyl group of these key intermediates into an amino group were unsuccessful. However 1,4-addition of thiolate and concomitant ring closure to isocoumarine provided a useful method for the transformation of the tertiary amide function. Opening of the isocoumarin with ammonia provided the corresponding amide and recovery of the enone system. Subsequent reductive amination of this cyclohexenone was found to depend on the nature of the protecting groups and led to the protected form of 4-epi- and -iso-narciclasine. Oxo analogues of narciclasine and epi-narciclasine and lycoricidine were also obtained after reduction of the enone and subsequent lactonization. They showed no biological activity as antitumor agents.",10.1021/jo049153l,2004-09-08,0.5828193194331067
Journal of Organic Chemistry,Conjugate Additions to Phenylglycinol-Derived Unsaturated δ-Lactams. Enantioselective Synthesis of Uleine Alkaloids,"The stereochemical outcome of the conjugate addition of a variety of stabilized nucleophiles (2-indoleacetic enolates and sulfur-stabilized anions) to the phenylglycinol-derived unsaturated lactams trans-2, cis-2, and its 8-ethyl-substituted analogue 10 is studied. The factors governing the exo or endo facial stereoselectivity are discussed. This methodology provides short synthetic routes to either cis- or trans-3,4-disubstituted enantiopure piperidines as well as efficient routes for the enantioselective construction of the tetracyclic ring system of uleine alkaloids, both in the normal and 20-epi series. The formal total synthesis of several alkaloids of this group is reported.",10.1021/jo0487101,2004-11-06,0.5828171654775397
Synthesis,"Efficient Multigram Syntheses of Air-Stable, Chiral Primary Phosphine Ligand Precursors via Palladium-Catalyzed Phosphonylation of Aryltriflates","Air-stable, chiral primary phosphines have been synthesized on a multigram scale. The key synthetic step is an optimized palladium-catalyzed phosphonylation reaction of aryltriflates, which opens up a valuable synthetic route to a chiral scaffold that is easily derivatized into novel phosphines.",10.1055/s-0032-1316825,2012-12-13,0.5828170183051847
Synlett,Synthesis of a Malimide Analogue of the Telomerase Inhibitor UCS1025A Using a Dianionic Aldol Strategy,International audience,10.1055/s-2007-968000,2007-02-01,0.5828137624325472
Organic Process Research & Development,Process Development of 5-Methoxy-1<i>H</i>-indole-2-carboxylic Acid from Ethyl 2-Methylmalonate,"Development is described of a new process for the preparation from malonates of 5-methoxy-1 H -indole-2-carboxylic acid esters, useful intermediates in the synthesis of pharmaceutical compounds. The process uses readily available starting materials, produces little waste, can be operated safely on at least 1 molar scale, and gives high yields. The main areas of optimization included the azo coupling of a diazonium salt with malonate derivatives, the Japp−Klingemann rearrangement, and the Fischer indole synthesis.",10.1021/op980006x,1998-04-30,0.5828129566709891
Organic Letters,"Enantioselective Synthesis of <i>N</i>-Cbz-Protected 6-Amino-6-deoxymannose, -talose, and -gulose",The enantioselective synthesis of three 6-amino-6-deoxy sugars has been achieved in six to eight steps from furfural. A sequence of diastereoselective oxidation and reduction reactions produced Cbz-protected 6-aminomannose from furfuryl alcohol 3. The incorporation of a Mitsunobu reaction into the reaction sequence allows for the selective synthesis of both N-Cbz-protected 6-aminotalose and 6-aminogulose. The overall procedure allows for the synthesis of either enantiomer of these three aminosugars. [reaction: see text],10.1021/ol016743m,2001-11-01,0.5828113516253818
Journal of Organic Chemistry,Ir-Catalyzed Allylic Amination/Ring-Closing Metathesis:  A New Route to Enantioselective Synthesis of Cyclic β-Amino Alcohol Derivatives,"Ir-catalyzed allylic aminations of (E)-4-benzyloxy-2-butenyl methyl carbonate with benzylamine using Feringa's (Sa,Sc,Sc)-phosphoramidite as a chiral ligand afforded linear-aminated achiral product N,O-dibenzyl-4-amino-2-buten-1-ol regioselectively (linear/branched = >99/1), whereas the (E)-5-benzyloxy-2-pentenyl methyl carbonate showed completely opposite regioselectivity (linear/branched = >1/99) and afforded the optically active (3R)-N,O-dibenzylated 3-amino-1-penten-5-ol with very high enantioselectivity (96% ee), which was used as a key intermediate for the effective synthesis of various cyclic beta-amino alcohol derivatives through ring-closing metathesis in high yields.",10.1021/jo070998h,2007-08-18,0.5828076589803075
Organic Letters,Chiral Auxiliaries for Asymmetric Radical Cyclization Reactions:  Application to the Enantioselective Synthesis of (+)-Triptocallol,"[figure: see text] A series of epimeric 8-aryl menthyl derivatives 5a-d and 6a-l, prepared from the same chiral source (R)-pulegone, were employed as chiral auxiliaries in the asymmetric radical cyclization reactions of beta-keto esters mediated by Mn(OAc)3. Chiral precursors 8c and 8d provided the cyclization products 10c and 10d, respectively, as single isomers (dr > 99:1), whereas the cyclization of precursor 9k gave 13k with good stereoselectivity (dr = 24:1). Diastereomer 13e was employed as the key intermediate in the enantioselective synthesis of (+)-triptocallol in 90% ee.",10.1021/ol0068243,2000-12-13,0.582804676708408
Organic Letters,Syntheses of G<sub>M4</sub> and G<sub>M3</sub> Intermediates via Alkylation and Subsequent Intramolecular Glycosidation of 2-Alkoxy-2-phenylthioacetate,We developed a new method for α-glycoside formation of sialyl conjugates based on alkylation and subsequent intramolecular glycosidation of 2-alkoxy-2-phenylthioacetate. By this method we succeeded in the syntheses of G M4 and G M3 intermediates.,10.1021/ol990245k,1999-11-09,0.5828014348578119
Tetrahedron,Highly convergent approach to the synthesis of the epoxy-amide fragment of the azinomycins,,10.1016/s0040-4039(00)79381-6,1991-07-01,0.5827994860501324
Organic Process Research & Development,"Practical Access to Key Intermediates of Crizotinib, Lorlatinib, and Pibrentasvir Enabled by Oxa-Spirocyclic Ligands","Optically active secondary alcohols are key building blocks for a variety of chiral drugs, and transition-metal-catalyzed asymmetric hydrogenation represents one of the most efficient and direct methods for the preparation of chiral secondary alcohols. We herein report a practical and efficient asymmetric hydrogenation catalyzed by a chiral iridium complex bearing ( R )- O -SpiroPAP as the ligand, producing intermediates of crizotinib, ensartinib, lorlatinib, and pibrentasvir in up to 99% yield with up to 99% ee and >20:1 dr. The synthetic potential of the current catalytic system was demonstrated by experiments on the gram and kilogram scales.",10.1021/acs.oprd.3c00089,2023-11-09,0.5827982028644888
Organic Process Research & Development,Process Development for the Synthesis of a Monobactam Antibiotic—LYS228,"A scalable process for the novel monobactam antibiotic LYS228 has been developed. This paper covers a novel scalable process for producing β-lactam 10 in the multiple kilogram scale. An alternative approach to compound 7 without protecting-group exchange has been demonstrated to enable a shortened synthesis. A scalable process for the side chain 20, which used an alternative reagent to mitigate a safety risk from the initial med-chem approach, was performed. The final assembling to LYS228, a stable isolated product, was identified and executed in the multiple kilogram scale.",10.1021/acs.oprd.9b00330,2020-02-07,0.5827975861922294
European Journal of Organic Chemistry,"Synthesis of the Insect Pheromone (2S,3S,7RS)-Diprionyl Acetate by Diastereoselective Protonation","The insect pheromone (2S,3S,7RS)-diprionyl acetate (1) was prepared from (S,S)-2,3-dimethylcyclohexanone (2), which in turn was obtained by the 1,4-addition of lithium dimethylcuprate to (S)-(+)-carvone (3) and diastereoselective protonation of the resulting enolate with phenyl salicylate, followed by removal of the isopropenyl group and hydrogenation. Baeyer−Villiger rearrangement of (S,S)-2 and opening of the lactone (S,S)-8 with octyllithium provided the hydroxy ketone (S,S)-9, which was transformed into the target molecule (2S,3S,7RS)-1 by carbonyl olefination with Petasis’ reagent, acylation and hydrogenation.",10.1002/1099-0690(200110)2001:20<3831::aid-ejoc3831>3.0.co;2-2,2001-10-01,0.5827970896671614
Tetrahedron,A new synthesis of trans-stilbenes,,10.1016/s0040-4039(01)98816-1,1968-01-01,0.5827968145099349
Journal of the American Chemical Society,Total Synthesis of (±)-Haouamine A,"The first total synthesis of the highly complex and potent anticancer agent haouamine A is reported through an eight-step sequence. Brevity of the sequence and complete control of chemo-, position-, and stereoselectivity (both planar and axial chirality) were possible through the invention of chemistry specifically tailored for the problems at hand, namely a cascade annulation proceeding via a hitherto unknown chemical entity for the indeno-tetrahydropyridine ring system as well as a pyrone-assisted stitching of the daunting bent-aromatic ring.",10.1021/ja0602997,2006-03-01,0.5827912505613859
Journal of Organic Chemistry,Synthesis of Cinnolines and Cinnolinium Salt Derivatives by Rh(III)-Catalyzed Cascade Oxidative Coupling/Cyclization Reactions,"A novel method for the synthesis of cinnolines and cinnolinium salt derivatives via Rh(III)-catalyzed cascade oxidative coupling/cyclization reaction from Boc-arylhydrazines and alkynes has been developed. The reactions have a broad substrate scope and high stereoselectivity with readily available starting materials and provides an efficient synthetic route for this kind of compounds. A catalytically competent five-membered rhodacycle has been isolated, thus revealing a key intermediate in the catalytic cycle.",10.1021/acs.joc.8b01548,2018-07-18,0.5827865518272142
Organic Letters,"Formal Fluorinative Ring Opening of 2-Benzoylpyrrolidines Utilizing [1,2]-Phospha-Brook Rearrangement for Synthesis of 2-Aryl-3-fluoropiperidines","A ring expansion of 2-benzoylpyrrolidines, which involves the formal fluorinative ring opening utilizing the [1,2]-phospha-Brook rearrangement under Brønsted base catalysis and a subsequent intramolecular reductive amination, was developed. The operationally simple three-step protocol provides an efficient access to 2-aryl-3-fluoropiperidines. The methodology was further applied to the syntheses of azepanes and tetrahydroquinolines.",10.1021/acs.orglett.1c02907,2021-09-29,0.5827830344895567
Angewandte Chemie International Edition,Potent Dual BET/HDAC Inhibitors for Efficient Treatment of Pancreatic Cancer,"Abstract As one of the most aggressive and lethal human malignancies with extremely poor prognosis, there is an urgent demand of more effective therapy for the treatment of pancreatic cancer. Reported here is a new, effective therapeutic strategy and the design of small‐molecule inhibitors that simultaneously target bromodomain and extra‐terminal (BET) and histone deacetylase (HDAC), potentially serving as promising therapeutic agents for pancreatic cancer. A highly potent dual inhibitor ( 13 a ) is identified to possess excellent and balanced activities against BRD4 BD1 (IC 50 =11 n m ) and HDAC1 (IC 50 =21 n m ). Notably, this compound shows higher in vitro and in vivo antitumor potency than the BET inhibitor (+)‐JQ1 and the HDAC inhibitor vorinostat, either alone or and in combination, highlighting the advantages of BET/HDAC dual inhibitors for more effective treatment of pancreatic cancer.",10.1002/anie.201915896,2020-01-14,0.5827805952602333
Organic Letters,Synthetic Studies toward the Bryostatins:  A Substrate-Controlled Approach to the A-Ring,[reaction: see text] The synthesis of a C1-C13 A-ring subunit of bryostatin 1 is detailed. The key features of the approach include the convergent fragment assembly with a highly stereoselective construction of the C7-C8 bond indicated above.,10.1021/ol061173h,2006-07-20,0.5827801641544293
Angewandte Chemie International Edition,Synthesis of Angularly Substituted <i>trans</i>‐Fused Decalins through a Metallacycle‐Mediated Annulative Cross‐Coupling Cascade,"A convergent coupling reaction is described that enables the stereoselective construction of angularly substituted trans-fused decalins from acyclic precursors. The process builds on our alkoxide-directed titanium-mediated alkyne-alkyne coupling and employs a 1,7-enyne coupling partner. Overall, the reaction is thought to proceed through initial formation of a tetrasusbstituted metallacyclopentadiene, stereoselective intramolecular [4+2] cycloaddition, elimination, isomerization, and regio- and stereoselective protonation. Distinct from our early studies directed at the synthesis of trans-fused hydrindanes, the current annulative coupling reveals an important effect of TMSCl in controlling the final protonation-the event that establishes the stereochemistry of the ring fusion.",10.1002/anie.201606962,2016-09-16,0.5827786624626227
Tetrahedron,Asymmetric total synthesis of (+)-cardiobutanolide via an iterative asymmetric dihydroxylation in PEG,,10.1016/j.tetlet.2010.05.122,2010-06-02,0.5827764432086626
Synthesis,"Asymmetric Reformatsky-Type Reaction of Isatin-Derived N-Sulfinyl Ketimines: Efficient and Practical Synthesis of Enantiopure Chiral 2-Oxoindolinyl-β3,3-Amino Esters","Optically pure 2-oxoindolinyl-β 3,3 -amino esters were obtained in good yields via highly efficient diastereoselective asymmetric Reformatsky-type reaction of isatin-derived chiral N -sulfinyl ketimines. The method is practical and allows rapid access to various important synthetic intermediates such as N -free 2-oxoindolinyl-β 3,3 -amino acid, spiro-β-lactam, and hexahydrofurano[2,3- b ]indole. It can also be used for the synthesis of gastrin/cholecyctokinin-B receptor antagonist AG-041R.",10.1055/s-0035-1561426,2016-04-18,0.5827762305789033
Organic Letters,Synthesis of Daucane Natural Products Enabled by a Gold(I)-Catalyzed Tandem Cycloisomerization/(4 + 3) Cycloaddition,"High Resolution Image Download MS PowerPoint Slide A divergent synthesis of three members of the daucane family of natural products is reported, enabled by a gold(I)-catalyzed cycloisomerization/formal (4 + 3) cycloaddition as the key step. The synthesis of penigrisacid A features a vanadium-catalyzed tandem epoxidation/S N 2′ cyclization, whereas a Suárez radical cyclization enables the synthesis of aspterric acid. This work has also led to the reassignment of the structure of penigrisacid A as well as a short formal synthesis of schisanwilsonene A.",10.1021/acs.orglett.4c04542,2025-02-27,0.5827760906469271
Journal of Organic Chemistry,Synthesis of a Hydroxyethylene Isostere of the Tripeptide Arg-Gly-Leu via a Convergent Acyl-like Radical Addition Strategy,"[reaction: see text] A hydroxyethylene isostere of the tripeptide Arg-Gly-Leu, representing an important fragment of a novel cyclic-peptide-based uPA inhibitor, was synthesized in few steps employing as the key step a samarium diiodide promoted coupling of either the 4-thiopyridyl ester of N(alpha)-Fmoc- or N(alpha)-Cbz-protected L-ornithine with the N-acryloyl derivative of L-leucine methyl ester. Epimerization under the coupling conditions at the chiral center in the alpha-position to the ketone was demonstrated not to take place. A stereoselective reduction of the Cbz-protected aminoketone obtained from this radical reaction was promoted by the same single-electron reducing agent in the presence of methanol providing the syn-amino alcohol with a diastereoselectivity of 85:15. With the use of lithium tri-tert-butoxyaluminum hydride in methanol, the corresponding anti-isomer was obtained almost exclusively. Subsequent elaboration of the ornithine moiety in the anti-isomer by introduction of the guanidine group followed by hydrolysis of the C-terminal ester bond and protection of the alcohol as its tert-butyldimethylsilyl ether provided the desired tripeptide mimic. The long reaction times required for the radical addition reactions with N(delta)-Boc-L-ornithine (up to 5 days) led to a short study where a series of 4-thiopyridyl esters of Cbz-protected amino acids were reacted with two acrylates. Whereas N(delta)-Boc-L-ornithine, alanine, phenylalanine, proline, and leucine all provided the aminoketone in 43-79% yield, valine only afforded traces of the coupling product.",10.1021/jo0505775,2005-08-20,0.582773711291444
Synlett,Synthetic Studies towards Leiodermatolide: Rapid Stereoselective Syntheses of Key Fragments,"The synthesis of three key fragments of the novel 16-membered macrolide leiodermatolide is described. The stereotetrad-containing building block was prepared via a Marshall-Tamaru reaction on an aldehyde obtained by organocatalysis. For a second building block, a Marshall-Tamaru reaction was used as well. The side-chain fragment containing a hydroxy δ-lactone could be obtained by intramolecular Reformatsky reaction.",10.1055/s-0030-1259286,2010-12-23,0.5827639167293284
Tetrahedron,Total synthesis of (±)-anatoxin-a via N-acyliminium intermediates,,10.1016/s0040-4039(00)85068-6,1986-01-01,0.5827567818881355
Journal of Organic Chemistry,Demethylative Lactonization Provides a Shortcut to High-Yielding Syntheses of Lamellarins,"Modular gram-scale syntheses of the trimethyl ethers of lamellarins G ( 6 ) and D ( 7 ) were achieved from readily accessible precursors in the highest overall yields reported to date ( 6, six steps, 82%; 7, seven steps, 86%). A novel demethylative lactonization between an aryl methyl ether and a neighboring carboxylic acid was developed for creating the chromenone unit of the targets to avoid the need for additional protection and deprotection steps. The central pyrrole core was constructed in a late-stage [4 + 1] condensation between ethyl bromoacetate and an enaminone possessing the remaining components of the lamellarin skeleton. Exhaustive demethylation of both permethyl ethers 6 and 7 gave the polyphenolic natural lamellarins A4 ( 3 ) and H ( 5 ), respectively.",10.1021/acs.joc.9b02983,2019-12-16,0.5827557994389911
Synthesis,Total Synthesis of the Z-Isomers of the Proposed and Revised Structures of Aspergillide B via an Iodocyclization and Ring-Closing Metathesis Strategy,"The synthesis of Z -isomers of both the proposed and revised structures of aspergillide B is described. A divergent route is employed that involves kinetically controlled ring-closing metathesis for the construction of a 14-membered macrocyclic ring, ester formation under Yamaguchi conditions, a Wacker-type oxidative cyclization for creation of the C4 stereogenic center and a previously reported diastereoselective isomerization–iodocyclization strategy for the construction of the 2,6- trans -disubstituted tetrahydropyran subunit.",10.1055/s-0033-1340853,2014-02-26,0.5827494765744533
Synlett,Elaboration of an Intermolecular Diels–Alder Adduct En Route to the Spiro-Fused Oroidin Alkaloids,"Abstract The dimeric oroidin alkaloids, exemplified by palau’amine, axinellamine, and massadine, remain challenging targets in the context of total synthesis owing to their compact and heteroatom-rich frameworks. A cycloaddition-rearrangement sequence has been developed using vinylimidazoles as substrates. The initial Diels–Alder adduct derived from urocanic acid and N-phenylmaleimide can be transformed into a lactone via a fluoride-induced ring-opening sequence. A twofold oxidation manifold affords the fully functionalized cyclopentane moiety present in palau’amine and congeners. Initial explorations to incorporate a second imidazole moiety are described.",10.1055/a-2644-2641,2025-07-30,0.5827477781252048
Tetrahedron,"Asymmetric aziridination with chiral allyl aminosulfoxonium ylides: synthesis of alkenyl aziridine carboxylates and palladium-catalyzed E,trans/E,cis-isomerization of an alkenyl aziridine",,10.1016/j.tetlet.2007.07.216,2007-08-07,0.5827434173292362
Journal of Organic Chemistry,Total Synthesis of the Proposed Microcyclamides MZ602 and MZ568,"The first convergent total synthesis for the proposed structures of microcyclamides MZ602 ( 1 ) and MZ568 ( 2 ) has been accomplished in 11 linear steps with 12.5 and 16.8% overall yield, respectively. Key features of the syntheses include a one-pot cascade reaction to construct core Boc- l -Ile-Thz-OAllyl fragment 5, and a removable pseudoproline (Ψ Me,Me pro) inducer assisted cyclization of thiazole-containing all- l linear peptides. The spectral data ( 1 H NMR, 13 C NMR, and HRMS) of synthetic MZ602 ( 1 ) were quite similar to those of the proposed natural microcyclamide MZ602, except to an opposite sign of the optical rotation value. Surprisingly, the synthetic MZ568 ( 2 ) presented large discrepancies in characteristic spectral data from those of the reported natural product, although the absolute configuration of key intermediate 36 was unambiguously determined by single-crystal X-ray analysis in our work. These findings revealed that the proposed structures of natural microcyclamides MZ602 and MZ568 required revision.",10.1021/acs.joc.0c02541,2020-12-09,0.5827402975264492
Journal of Organic Chemistry,<i>gem</i>-Difluorination of Aminoalkynes via Highly Reactive Dicationic Species in Superacid HF−SbF<sub>5</sub>:  Application to the Efficient Synthesis of Difluorinated Cinchona Alkaloid Derivatives,"A variety of alkynylated amines, amides, and imides are reacted in the superacid system HF-SbF5 to give regioselectively new beta-gem-difluoroamines. The reaction, which is not observed in pure HF, is consistent with the formation of a dicationic intermediate (i.e., both vinylic and adjacent protonated N-ammonium cations). Application to the regioselective and efficient synthesis of difluorinated cinchona alkaloid derivatives is described.",10.1021/jo702441p,2008-03-04,0.5827368780759478
Tetrahedron,"An efficient route to 1α,25-dihydroxyvitamin D3 functionalized at C-11",,10.1016/s0040-4039(00)77685-4,1992-01-01,0.582736724751757
Tetrahedron,"Asymmetric synthesis VII: enantiospecific preparation of β-aminoalcohols from the n-cyanomethyl-4-phenyl-1,3-oxazolidine synthon",,10.1016/s0040-4039(01)84595-0,1985-01-01,0.5827364441540124
Synlett,Lycopodium Alkaloids: An Intramolecular Michael Reaction Approach,"The Lycopodium alkaloids possess a rich history that has captured the attention of synthetic chemists across the globe. This large family consists of over 250 known natural products with diverse structural features and noteworthy biological activity. Herein, we interweave the synthetic accomplishments by others in the field with our own unified strategy to accessing multiple subfamilies of the Lycopodium alkaloids. This discussion includes lycopodine, the C10-hydroxy Lycopodium alkaloids (10-hydroxylycopodine, deacetylpaniculine and paniculine), pelletierine, cermizine D, fastigiatine, himeradine A, clavolonine and 7-hydroxylycopodine. A unifying feature of much of the work discussed within this account is the use of intramolecular Michael additions to construct key ring systems within the Lycopodium alkaloids. Examples include the use of an intramolecular keto-sulfone Michael reaction and an intramolecular heteroatom Michael reaction. 1 General Background on Lycopodium Alkaloids 2 Development of a Strategy for Lycopodium Alkaloids 2.1 Generalized Strategy 2.2 Known Syntheses of C10-Functionalized Lycopodium Alkaloids 3 Quinolizidine-Type Alkaloids 3.1 Background 3.2 Development of the Heteroatom Michael Reaction 3.3 Synthesis of the Core Lycopodine Building Block: Pelletierine 3.4 Total Synthesis of Cermizine D 3.5 Synthesis of the Eastern Half of Himeradine A 4 Lycopodine-Type Alkaloids 4.1 Total Syntheses of Lycopodine 4.1.1 Earlier Racemic Syntheses 4.1.2 Approach Toward the Tricyclic Skeleton of Lycopodine: Intramolecular Mannich 4.1.3 Enantioselective Total Syntheses of Lycopodine 4.2 Total Syntheses of Clavolonine (8-Hydroxylycopodine) 4.3 Total Synthesis of 7-Hydroxylycopodine 4.4 Synthetic Route for 10-Hydroxy Lycopodium Alkaloids 4.4.1 Background 4.4.2 Total Syntheses 4.4.3 Impact of the C10-Stereochemistry 5 Conclusion",10.1055/s-0036-1588851,2017-06-06,0.582729047428201
Angewandte Chemie International Edition,"Total Synthesis of the Natural Enantiomer of (â)-Lepadiformine and Determination of Its Absolute Stereochemistry This work was supported in part by a Grant for Private Universities provided by the Ministry of Education, Sports, and Culture of Japan and the Promotion and Mutual Aid Corporation for Private Schools of Japan. We are grateful to Professor J. F. Biard for a sample of natural lepadiformine.","A short synthesis: The naturally occurring (−)-lepadiformine ((−)-3) was prepared in nine steps in 31.4 % overall yield. The key step involved the formation of 2 by the spirocyclization of the N-acyliminium ion generated from 1. Furthermore, HPLC analysis of the synthetic material and the natural product established the absolute configuration of 3 as 3S,5R,7aS,11aS. Bn=benzyl, Boc=tert-butoxycarbonyl.",10.1002/1521-3773(20020816)41:16<3017::aid-anie3017>3.0.co;2-1,2002-08-16,0.5827270030203645
Angewandte Chemie International Edition,Efficient Construction of the Clerodane Decalin Core by an Asymmetric Morita–Baylis–Hillman Reaction/Lewis Acid Promoted Annulation Strategy,"Linking rings: A general route toward the clerodane diterpene core using an asymmetric Morita-Baylis-Hillman (MBH)/Lewis acid mediated ring-annulation process has been developed. The scope of the asymmetric Brønsted acid catalyzed MBH reaction has been expanded to include silane-containing aldehydes, which are elaborated into the trans decalin core in high diastereo- and enantioselectivities.",10.1002/anie.200601076,2006-06-27,0.582726533428936
Angewandte Chemie International Edition,"Enantioselective Synthesis of Oasomycin A, Part III: Fragment Assembly and Confirmation of Structure","Putting the pieces together: The total synthesis of the natural macrolide oasomycin A has been realized. Key fragment couplings include an anti-Felkin selective aldol addition (green), Kociensky–Julia olefinations (red), and competitive Weinreb amide acylation reaction (blue). The utility of the 4,5-diphenyloxazole as a carboxy surrogate and the late-stage macrolactonization affording the 42-membered macrocycle of oasomycin A are also described.",10.1002/anie.200603652,2006-12-08,0.5827228440927271
Journal of the American Chemical Society,Total Synthesis of (±)-Trigonoliimine C via Oxidative Rearrangement of an Unsymmetrical Bis-Tryptamine,"We report the first total synthesis of (±)-trigonoliimine C, a member of a family of structurally complex alkaloids, in 10 steps from tryptamine and 6-methoxytryptamine. Our convergent synthetic strategy relies on a selective oxidative rearrangement of an unsymmetrical 2,2'-bis-tryptamine.",10.1021/ja203960b,2011-06-14,0.5827211795156317
European Journal of Organic Chemistry,"Expeditious Racemic and Enantiodivergent Synthesis of 1‐Deoxymannojirimycin and 1,4‐Dideoxymannojirimycin","Abstract The racemic and enantiodivergent syntheses of 1‐deoxymannojirimycin (DMJ) and 1,4‐dideoxymannojirimycin have been realized through key enamide ester intermediates obtained by converting cis ‐4,5‐dihydroxylated δ‐valerolactam derivatives into the corresponding enol phosphates and subjecting them to Pd‐catalyzed methoxycarbonylation. Further elaborations of these intermediates included stereocontrolled catalytic hydrogenation, for the synthesis of racemic 1,4‐dideoxymannojirimycin, and hydroboration/oxidation, for the synthesis of DMJ. Enantiodivergency was attained by optical resolution before exhaustive functional group deprotection, through the formation of diastereomeric camphanic esters. As the key racemic intermediate esters were easily prepared in a few steps on a large scale, and the final chromatographic separation of the camphanic esters was straightforward, this approach represents a convenient way to obtain both enantiomers of DMJ for medicinal chemistry studies.",10.1002/ejoc.201200022,2012-03-14,0.5827151345263052
Organic Letters,Caged <i>trans</i>-4-Hydroxy-2-nonenal,"[reaction: see text] A caged 4-hydroxy-2-nonenal (4-HNE) has been prepared and its photochemistry investigated. Upon photolysis, 1 releases 4-HNE in up to 100% yield. From these photolyses, 4-HNE could be isolated in up to 91% yield. 4-HNE is produced under either aerobic or anaerobic conditions. The caging strategy does not require prior preparation of 4-HNE and, therefore, represents a three-step synthetic route to the bioactive enal in 48% overall yield.",10.1021/ol048478l,2004-09-16,0.5827127907222036
Tetrahedron,A stereoselective route to enantiomerically pure myo-inositol derivatives starting from D-mannitol,,10.1016/s0040-4039(00)76674-3,1994-05-01,0.5827076286519307
Angewandte Chemie International Edition,"A Divergent Polyene Cyclization for the Total Synthesis of Greenwayodendrines, Greenwaylactams, Polysin and Polyveoline","We present a concise asymmetric total synthesis (5-8 steps) of nine sesquiterpenoid alkaloids featuring four different tetra-/pentacyclic scaffolds. To this end, a novel, bioinspired indole N-terminated cationic tricyclization has been developed, enabling the divergent synthesis of greenwayodendrines and polysin. Subtle variation of the C2-substituted indole cyclization precursor allowed switching between indole N- and C-termination. For the latter, a subsequent Witkop oxidation enabled conversion of the cyclopentene-fused indole into the eight-membered benzolactam to directly furnish the family of greenwaylactams. In addition, a diastereomeric C-termination product has been elaborated to provide access to polyveoline.",10.1002/anie.202307719,2023-06-15,0.5827051408941814
Tetrahedron,"One-pot synthesis of γ-butyrolactones and 4,5-dihydrofurans from α-chloro-α-ketosulfides and olefins",,10.1016/s0040-4039(00)81752-9,1983-01-01,0.5827049777726042
Tetrahedron,Synthesis of isoquinuclidinones via a tandem amination/imination sequence: application to the synthesis of (−)-mearsine,,10.1016/j.tetlet.2010.08.052,2010-08-23,0.582701196391404
Tetrahedron,"Cycloaromatization of α-oxoketene dithioacetals with lithioacetonitrile: A facile route for 4-substituted and 4,5-annelated pyridines",,10.1016/s0040-4039(00)82416-8,1988-01-01,0.5827010079555018
Tetrahedron,"Asymmetric hydrogenation of methyl 3,5-dioxohexanoate catalyzed by ru-binap complex: a short step asymmetric synthesis of dihydro-60methyl-2-H-pyran-2-one",,10.1016/0040-4039(91)80569-r,1991-12-01,0.5827005151481881
Organic Letters,Synthesis of the C16−C35 Fragment of Integramycin Using Olefin Hydroesterification as a Linchpin Reaction,"[reaction: see text] The spiroketal unit of the HIV-integrase inhibitor integramycin has been prepared in an efficient and convergent manner. Key steps in this sequence include the use of ruthenium-mediated hydroesterification reactions of homoallylic alcohols and silyl ethers, and a C,O-dianionic addition into a lactone provides the spiroketal while minimizing protecting group manipulations.",10.1021/ol036339i,2004-01-27,0.582697962431497
Journal of Organic Chemistry,"New, Improved Procedure for the Synthesis of Structurally Diverse <i>N</i>-Spiro <i>C</i><sub>2</sub>-Symmetric Chiral Quaternary Ammonium Bromides","Selective, direct ortho magnesiation of (S)-2,2'-bis(isopropoxycarbonyl)-1,1'-binaphthyl (6) has been achieved under mild conditions, using magnesium bis(2,2,6,6-tetramethylpiperamide) [Mg(TMP)(2)]. In combination with the subsequent reaction with the appropriate electrophiles, bromine and iodine, this method constitutes a key step in establishing a new and concise synthetic route to a wide variety of N-spiro C(2)-symmetric chiral quaternary ammonium bromides of type 1.",10.1021/jo030032f,2003-05-01,0.582695717169456
Journal of Organic Chemistry,"Asymmetric Total Syntheses of (+)-5-<i>epi</i>-Schisansphenin B and the Proposed Structure of (+)-15-Hydroxyacora-4(14),8-diene","The asymmetric total syntheses of (+)-5- epi -schisansphenin B and the proposed structure of (+)-15-hydroxyacora-4(14),8-diene have been accomplished from 1,3-cyclopentadione ( 10 ) in eight synthetic steps. The enantioselective palladium-catalyzed redox-relay Heck alkenylation, the intramolecular Stetter reaction, and the regioselective Tiffeneau–Demjanov-type ring expansion were the pivotal steps in these syntheses.",10.1021/acs.joc.1c02627,2021-12-23,0.5826952668278726
Tetrahedron,"Stereo-selective synthesis of Erythro-3-methyl-hexyn-3,4-diol",,10.1016/s0040-4039(00)85755-x,1982-01-01,0.5826928263324692
Tetrahedron,Use of trityl thiol for stereoselective thioester synthesis: a new preparation of (S)-thiolactic acid,,10.1016/s0040-4039(00)00249-5,2000-04-01,0.5826891843135129
Synlett,"Enantioselective Access to the Mycotoxin, Aflatoxin B<sub>2</sub>","All articles of this category Enantiomerically enriched tetrahydrofuro[2,3- b ]benzofuran ( 2 ), a penultimate intermediate in the synthesis of optically active aflatoxin B 2 , has been synthesized employing the lipase-catalyzed asymmetric acetylation of the prochiral diol as the key step. aflatoxin B 2 - enantioselective synthesis - lipase enzymatic acetylation - prochiral diol",10.1055/s-1997-3266,1997-06-01,0.5826878030117342
Green Chemistry,Biocatalytic asymmetric ring-opening of dihydroisoxazoles: a cyanide-free route to complementary enantiomers of β-hydroxy nitriles from olefins,"From alkenes and nitromethane, a cyanide-free pathway to synthesize chiral β-hydroxy nitriles <italic>via</italic> the enantioselective ring-opening of 5-sub-4,5-dihydroisoxazoles catalyzed by aldoxime dehydratases has been developed.",10.1039/d0gc01445a,2020-01-01,0.5826867630037419
European Journal of Organic Chemistry,"An Efficient Synthesis of (R)-3-{(R)-3-[2-O-(α-L-Rhamnopyranosyl)- α-L-rhamnopyranosyl] oxydecanoyl}oxydecanoic Acid, a Rhamnolipid fromPseudomonas Aeruginosa","N-iodosuccinimide/triflic acid mediated one-pot two-step glycosylation of ethyl 2,3,4-tri-O-benzyl-1-thio-α-L-rhamnopyranoside (8) with phenyl 3,4-O-(2,3-dimethoxybutane-2,3-diyl)-1-thio-α-L-rhamnopyranoside (10b) and phenacyl (R)-3-hydroxydecanoate (13) gave rhamnolipid 17. The latter was transformed in five steps into the title compound 2. Esterification of 2 with diazomethane resulted into the corresponding methyl ester derivative 1.",10.1002/(sici)1099-0690(199802)1998:2<303::aid-ejoc303>3.0.co;2-u,1998-02-01,0.5826831666675293
European Journal of Organic Chemistry,"An Efficient Synthesis of (R)-3-{(R)-3-[2-O-(α-L-Rhamnopyranosyl)- α-L-rhamnopyranosyl] oxydecanoyl}oxydecanoic Acid, a Rhamnolipid from Pseudomonas Aeruginosa","N-iodosuccinimide/triflic acid mediated one-pot two-step glycosylation of ethyl 2,3,4-tri-O-benzyl-1-thio-α-L-rhamnopyranoside (8) with phenyl 3,4-O-(2,3-dimethoxybutane-2,3-diyl)-1-thio-α-L-rhamnopyranoside (10b) and phenacyl (R)-3-hydroxydecanoate (13) gave rhamnolipid 17. The latter was transformed in five steps into the title compound 2. Esterification of 2 with diazomethane resulted into the corresponding methyl ester derivative 1.",10.1002/(sici)1099-0690(199802)1998:2<303::aid-ejoc303>3.3.co;2-l,1998-02-01,0.5826831666675293
Organic Process Research & Development,"One-Pot Synthesis of 5-Methyl-3H-pyrrolo[2,3-<i>d</i>]pyrimidin-4(7H)-one","An efficient and environmentally benign synthesis of 5-methyl-3H-pyrrolo[2,3- d ]pyrimidin-4(7H)-one is described. An acyl-protected aminoacetone is reacted with cyanoacetamide to give 2-amino-4-methyl-1H-pyrrole-3-carboxamide, which is converted in one-pot to 5-methyl-3H-pyrrolo[2,3- d ]pyrimidin-4(7H)-one in 60% overall yield. This process avoids the use of large excess Raney nickel which is required when known methods are practiced.",10.1021/op060207y,2006-12-13,0.582676253604182
Journal of the American Chemical Society,"Enantioselective Total Synthesis of Antibiotic CJ-16,264, Synthesis and Biological Evaluation of Designed Analogues, and Discovery of Highly Potent and Simpler Antibacterial Agents","An improved and enantioselective total synthesis of antibiotic CJ-16,264 through a practical kinetic resolution and an iodolactonization reaction to form the iodo pyrrolizidinone fragment of the molecule is described. A series of racemic and enantiopure analogues of CJ-16,264 was designed and synthesized through the developed synthetic technologies and tested against drug-resistant bacterial strains. These studies led to interesting structure-activity relationships and the identification of a number of simpler, and yet equipotent, or even more potent, antibacterial agents than the natural product, thereby setting the foundation for further investigations in the quest for new anti-infective drugs.",10.1021/jacs.7b08749,2017-10-24,0.5826670451100909
Journal of Organic Chemistry,Synthesis of Ring-Fused Oxazolo- and Pyrazoloisoquinolinones by a One-Pot Pd-Catalyzed Carboxamidation and Aldol-Type Condensation Cascade Process,"A three-component cascade process is described for the synthesis of ring-fused oxazolo- and pyrazoloisoquinolinones by a one-pot carboxamidation/aldol-type condensation reaction. The cascade process involves Pd-catalyzed carboxamidation of an aryl halide/active methylene compound with oxazolidinone or pyrazolidinone, and subsequent intramolecular base-catalyzed cyclization/dehydration through an aldol-type condensation process, to give ring-fused oxazolo- and pyrazoloisoquinolinones. This methodology provides an easy one-step approach to these important classes of nitrogen-containing heterocycles and can tolerate a wide array of functional groups, including ester, nitrile, methoxy, and halide.",10.1021/jo9010574,2009-07-17,0.5826636393626344
Journal of the American Chemical Society,Total Synthesis of (±)-Crokonoid A,"We report the first total synthesis of (±)-crokonoid A, a highly oxidized and rearranged ent -kauranoid featuring a novel tricyclo[4.4.1.1 1,4 ]dodecane scaffold. The unique double bridged carbon skeleton was assembled by synthesis of the bicyclo[4.3.1]decane via nitrile-oxide dipolar cycloaddition. Salient features of this strategy are the effective construction of the bridged system and masking the twofold aldol motif as an isoxazoline. An unconventional bridgehead propargylation set the key quaternary stereocenter concomitant with the installation of the side chain. Subsequent cycloalkenylation led to construction of the bicyclo[3.2.1]octane, completing the carboskeleton. Strategic orchestration involving regio- and diastereoselective reactions furnished the unique oxidation pattern, thus completing the total synthesis.",10.1021/jacs.5c11026,2025-08-15,0.5826574220313657
Organic Process Research & Development,An Improved Process for the Preparation of Trimethylhydrazine and Its Coupling with an Activated Acid Intermediate,"Trimethylhydrazine (TMH) was prepared in two steps from 1,1-dimethylhydrazine, using an easy to scale-up procedure that avoided difficult acid−base extractions. The procedure provided TMH as a solution in 1,4-dioxane, in a form that was easy and safe to handle in a coupling with an enantiomerically pure, sterically hindered, Boc-protected-amino acid, 1 . This key coupling reaction in the preparation of 3 was accomplished through the corresponding acid chloride, thereby avoiding the use of expensive coupling reagents.",10.1021/op0342022,2004-03-26,0.5826570148134346
Synthesis,"Phenanthro[9,10‑d]imidazoles: An Unexpected Synthetic Route","Abstract A new synthetic route for the synthesis of phenanthro[9,10‑d]imidazoles is described. Through aminolysis of easily accessible 10,10-diazidophenanthren-9(10H)-one with nucleophilic amines, a self-condensation is triggered that results in the formation of the target phenanthro[9,10‑d]imidazoles. The molecular structures were studied by X-ray single crystallography, and the optical properties of the material are described.",10.1055/s-0042-1751493,2023-10-05,0.5826559153687746
Organic Letters,"Synthesis of 2-Difluoroethylated 2<i>H</i>-1,3-Benzoxazines via Proton-Mediated Ring Opening/Interrupted Ritter Reaction of 1,1-Difluorocyclopropanes","2-(1,1-Difluoroethyl)-2 H -1,3-benzoxazines were synthesized by (i) the regioselective ring opening of 1,1-difluorocyclopropanes bearing an aryloxy group and (ii) the Ritter reaction followed by a Friedel–Crafts-type ring closure. When 2-aryloxy-1,1-difluorocyclopropanes were treated with triflic acid, the C–C bond distal to the CF 2 moiety was cleaved regioselectively via protonation to generate the corresponding oxocarbenium ions. These intermediates readily underwent nucleophilic attack by nitriles, followed by a carbocationic cyclization to afford the 2-difluoroethylated benzoxazines.",10.1021/acs.orglett.3c01277,2023-06-05,0.5826517874180919
Synlett,"Synthesis of the First Representatives of Thieno[3,2-c][1,7]naphthyridine Derivatives Based on 3-Amino-6-methyl-4-(2-thienyl) pyridin-2(1H)-one","A one-pot method for obtaining novel thieno[3,2-c][1,7]naphthyridine derivatives based on the reaction of 3-amino-4-(thien-2-yl)pyridin-2(1H)-one with aromatic aldehydes in 80% ­phosphoric acid at 130 °C has been developed. The formation of the thieno[3,2-c][1,7]naphthyridine ring was due to the intermediate generation of the corresponding azomethine, which underwent intra­molecular cyclization with electrophilic attack of the β-carbon atom of the thiophene core under Pictet–Spengler conditions. The isolated 5,7-dihydrothieno[3,2-c][1,7]naphthyridin-4(3H)-ones underwent oxidative aromatization in air to give thieno[3,2-c][1,7]naphthyridin-6(7H)-ones. A two-step synthesis of thieno[3,2-c][1,7]naphthyridines involving the isolation of the intermediate imine did not lead to a significant increase in the product yield.",10.1055/s-0037-1610445,2018-07-02,0.5826499199572609
Synthesis,"Activated Nitriles in Heterocyclic Synthesis: Novel Synthesis of Pyridazines, Pyridines, and Isoxazoles",,10.1055/s-1982-29850,1982-01-01,0.58264643124
Angewandte Chemie International Edition,Enantioselective Total Synthesis of (+)‐Homochelidonine by a Pd<sup>II</sup>‐Catalyzed Asymmetric Ring‐Opening Reaction of a <i>meso</i>‐Azabicyclic Alkene with an Aryl Boronic Acid,"An efficient and highly convergent enantioselective synthesis of (+)-homochelidonine has been achieved (see scheme; Cbz=benzyloxycarbonyl, MOM=methoxymethyl) and relied on a new and powerful desymmetrizing ring-opening reaction of a meso-azabicycle with an aryl boronic acid. The route should allow access to other hexahydrobenzo[c]phenanthridine alkaloids.",10.1002/anie.200603945,2006-12-05,0.5826450546305021
Tetrahedron,Synthesis and synthetic applications of 1-(3-O-tosyl-β-d-glucopyranosyl) thymines: toward new classes of hexopyranosyl pyrimidines,,10.1016/j.tetlet.2003.12.153,2004-02-04,0.5826427045721112
Organic Letters,Access to Both Anomers of Pectenotoxin Spiroketals by Kinetic Spiroketalization,"[structure: see text] A concise synthesis of both AB ring spiroisomers of the pectenotoxins is described. The nonanomeric AB spiroketal ring system of the pectenotoxins-1, -2, -3, and -6 is formed under very mild, kinetic spiroketalization conditions, along with the anomeric isomer. Only catalytic asymmetric transformations were used as the source of chirality in the synthesis route.",10.1021/ol048321t,2004-09-11,0.5826372537283928
Organic Letters,Efficient and Stereoselective Access to the Polyol Fragment C9−C16 of Ansamycin Antibiotics,"Efficient synthesis of the fragment C9-C16 bearing the anti,syn stereotriad of ansamycin antibiotics is described. Key steps for controlling the configuration of the three stereogenic centers involve a stereoselective Reformatsky-type reaction followed by a diastereoselective reduction of a beta-ketosulfoxide.",10.1021/ol901144j,2009-07-22,0.5826350930746531
Journal of Organic Chemistry,"General and Modular Synthesis of Isomeric 5-Substituted Pyridin-2-yl and 6-Substituted Pyridin-3-yl <i>C</i>-Ribonucleosides Bearing Diverse Alkyl, Aryl, Hetaryl, Amino, Carbamoyl, and Hydroxy Groups","A general modular and practical methodology for preparation of diverse 5-substituted pyridin-2-yl and 6-substituted pyridin-3-yl C-ribonucleosides was developed. Regioselective lithiation of 2,5-dibromopyridine proceeded at position 5 or 2 depending on the solvent, and the resulting bromopyridyl lithium species underwent additions to TBS-protected ribonolactone and follow-up transformations to corresponding acetylated hemiketal intermediates 7 and 10 that were diastereoselectively reduced to give either 5-bromopyridin-2-yl or 6-bromopyridin-3-yl silyl-protected C-ribonucleosides 8 or 11 in 68% and 77% overall yields as pure β-anomers. These bromopyridyl C-nucleoside intermediates were then subjected to a series of palladium-catalyzed cross-coupling reactions, aminations, aminocarbonylations, and hydroxylations to give a series of protected 1β-(5-alkyl-, 5-aryl-, 5-amino-, 5-carbamoyl-, and 5-hydroxypyridin-2-yl)-C-ribonucleosides 13a-i and β-(6-alkyl-, 6-aryl-, 6-amino-, 6-carbamoyl-, and 6-hydroxypyridin-3-yl)-C-ribonucleosides 15a-i. Deprotection of silylated nucleosides by Et(3)N·3HF, TBAF, or TFA gave a series of free C-nucleosides 14a-i and 16a-i.",10.1021/jo200949c,2011-07-08,0.5826324734614033
Organic Process Research & Development,Practical Synthesis of MDM2 Antagonist RG7388. Part 2: Development of the Cu(I) Catalyzed [3 + 2] Asymmetric Cycloaddition Process for the Manufacture of Idasanutlin,"A concise catalytic asymmetric synthesis of idasanutlin ( 1 ) was developed in which the key pyrrolidine core, containing four contiguous stereocenters, was constructed via a Ag/MeOBIPHEP promoted [3 + 2] cycloaddition reaction. Further development of the [3 + 2] cycloaddition reaction resulted in an improvement in diastereoselectivity and enantioselectivity by changing the catalyst system to Cu(I)/BINAP. While producing equivalent high quality API, the copper(I) catalyzed process not only increased the overall yield but also demonstrated benefit with respect to cycle times, waste streams, and processability. The optimized copper(I) catalyzed process has been used to prepare more than 1500 kg of idasanutlin ( 1 ).",10.1021/acs.oprd.6b00319,2016-10-31,0.5826317929081054
Journal of Organic Chemistry,"Improved Synthesis of the Unnatural Amino Acids AHMOD and AMD, Components of the Anticancer Peptaibol Culicinin D","An improved second-generation synthesis of the unnatural amino acid components of the anticancer peptaibol culicinin D has been developed. With a protected glutamic acid derivate as the starting material, the process readily delivered the Fmoc-protected free acid derivatives of AHMOD ((2S)-amino-(6R)-hydroxy-(4S)-methyl-8-oxodecanoic acid) and AMD ((2S)-amino-(4S)-methyldecanoic acid) required to support solid phase peptide synthesis (SPPS) for structure-activity studies of the natural product. The same approach also provides improved access to pipecolic acid derivatives. A novel Wittig reagent for one-carbon homologation of aldehydes, developed during this work, is also reported.",10.1021/acs.joc.5b01265,2015-08-07,0.5826296073558853
Organic Letters,Stereoselective Synthesis of Heavily Hydroxylated Azepane Iminosugars via Osmium-Catalyzed Tethered Aminohydroxylation,"A novel stereoselective synthetic approach to pentahydroxyazepane iminosugars is described. The strategy relies on a key osmium-catalyzed aminohydroxylation reaction of allylic alcohols obtained via addition of vinylmagnesium bromide to a d-mannose-derived aldehyde, which forms the new C-N bond with complete regio- and stereocontrol according to the tethering approach. Subsequent intramolecular reductive amination afforded the desired azepanes. This method represents the first application of the osmium-catalyzed tethered aminohydroxylation reaction to the synthesis of iminosugars.",10.1021/acs.orglett.3c02087,2023-07-29,0.5826218199015838
Organic Letters,"Formation of the Corannulene Core by Nickel-Mediated Intramolecular Coupling of Benzyl and Benzylidene Bromides:  A Versatile Synthesis of Dimethyl 1,2-Corannulene Dicarboxylate","[reaction: see text] A practical synthesis of dimethyl 1,2-corannulene dicarboxylate (5) is reported, with the final ring-forming step achieved by the double intramolecular nickel powder mediated coupling of benzyl and benzylidene bromide groups with 60% isolated yield.",10.1021/ol026457q,2002-08-15,0.5826214645687465
Synthesis,"A Novel Alkylation of Alicyclic 1,2-Enediolates. A Facile Synthesis of Oxoalkanenitriles",,10.1055/s-1976-24046,1976-01-01,0.5826163355371549
Organic Letters,Application of a Raney-Cobalt-Mediated Tandem Reductive Cyclization Protocol to Total Syntheses of the <i>Aspidosperma</i> Alkaloids (±)-Limaspermidine and (±)-1-Acetylaspidoalbidine,The racemic modification of the Aspidosperma alkaloid limaspermidine (1) has been prepared in ten steps including one involving a Raney-cobalt-mediated tandem reductive cyclization of nitrile 8 to give the tetracyclic system 9b. Compound (±)-1 has been converted over two steps into (±)-1-acetylaspidoalbidine [(±)-13].,10.1021/ol3026846,2012-10-30,0.582614060630628
Organic Letters,Synthesis of (±)-Bistellettadine A,Esterification of the trienoic acid with o-xylylene dibromide gave the bis ester that underwent a templated Diels-Alder reaction to afford the macrodiolide stereospecifically in a single step. The synthesis of bistellettadine A was completed in four steps by hydrolysis and side chain elaboration.,10.1021/ol902895e,2010-01-15,0.5826137414920932
Angewandte Chemie International Edition,Convergent Assembly of the Tricyclic Labdane Core Enables Synthesis of Diverse Forskolin‐like Molecules,"We report a new synthetic strategy for the flexible preparation of forskolin-like molecules. The approach is different from the previously published works and employs a convergent assembly of the tricyclic labdane-type core from pre-functionalized cyclic building blocks. Stereoselective Michael addition enabled the fragment coupling with excellent control over three newly created contiguous stereocenters, all-carbon quaternary centers included. Silyl enol ether-promoted ring-opening metathesis paired with ring closure were the other key steps enabling concise assembly of the tricyclic core. Late-stage functionalization sequences transformed the tricyclic intermediates into a set of different forskolin-like molecules. The modular nature of the synthetic scheme described herein has the potential to become a general platform for the preparation of analogs of forskolin and other complex tricyclic labdanes.",10.1002/anie.202213183,2022-11-02,0.5826117100193814
Synlett,Flexible and Stereocontrolled Synthesis of Azasugars with Novel Substitution Patterns,"All articles of this category Polyhydroxylated piperidines (azasugars) with novel substitution patterns are synthesized in high diastereo- and enantiomeric excesses by α,α′ -double alkylation of 2,2-dimethyl- 1,3-dioxan-5-one using the SAMP-/RAMP -hydrazone method and subsequent piperidine ring formation through reductive amination.",10.1055/s-1992-21562,1992-01-01,0.5826103624191009
Journal of Organic Chemistry,"A Synthesis of C(16),C(18)-Bis-<i>epi</i>-cytochalasin D via Reformatsky Cyclization","Triene 5 has been prepared by the E-selective olefination of aldehyde 12 with the ylide 11. Several alternative syntheses of 12 were evaluated, and the successful route involved conversion of 22 into the vinyl ether 23 by Petasis olefination, followed by Claisen rearrangement. Diels-Alder cycloaddition of 5 with 4 gave the adduct 6 in 77% yield, and Reformatsky cyclization under dilution conditions afforded 10 (67%). After conversion to enol silane 32, oxidation with dimethyldioxirane produced 34. Conversion to a key intermediate 38 using electrophilic selenenylation and selenoxide rearrangement, followed by enolate alkylation and deprotection, gave 43. The X-ray crystal structure of 43 was determined to prove the stereochemistry.",10.1021/jo000533q,2000-08-22,0.5826098558565826
Synlett,"Diastereo- and Enantioselective Synthesis of<i>syn</i>-2,3-Disubstituted 1,4-Diketones<i>via</i>Oxidative Coupling of Metalated Hydrazones","All articles of this category An efficient diastereo- and enantioselective synthesis of syn -2,3-disubstituted 1,4-diketones 4 is described. Key step of the procedure is the oxidative coupling of the metalated SAMP/RAMP-hydrazones 2 with iodine, followed by oxidative cleavage of the dimerized bishydrazones 3 with ozone and subsequent separation of the minor meso -isomer by chromatography. The d , l -isomers of the title 1,4-diketones 4 are obtained in good overall yields (20-64%) and high diastereo- and enantiomeric excesses ( de ≥ 98%, ee = 80- ≥ 95%). 1,4-diketones - asymmetric synthesis - oxidative coupling - SAMP/RAMP hydrazone method",10.1055/s-1998-1562,1998-01-01,0.5826080072522404
European Journal of Organic Chemistry,A Tandem Asymmetric Friedel–Crafts Alkylation/Michael Addition: Synthesis of Novel Ergoline Derivatives,"Herein, we report the development of an asymmetric tandem Friedel–Crafts alkylation/Michael addition of 4‐substituted indoles with trans ‐β‐nitrostyrene derivatives. By employing a chiral Zn II ‐(bis)oxazoline catalyst we could control the formation of three contiguous chiral centers in one step in 57 %–99 % yield and up to &gt; 99 % ee . This methodology provides easy access to a range of novel C 4 ‐substituted products containing the tricyclic core of the ergoline skeleton and allows for the synthesis of tetracyclic ergoline derivatives with four chiral centers, in high enantioselectivity and as single isolated diastereomers.",10.1002/ejoc.201901007,2019-08-16,0.5825964471949394
Tetrahedron,Generation and intramolecular cyclization of (2-ethenylphenyl)bisketenes. Synthesis of benzofuranones,,10.1016/s0040-4039(98)00638-8,1998-05-01,0.5825937792465524
European Journal of Organic Chemistry,"1-Methyl-1-azacyclohexa-2,3-diene(N−B)borane − Generation and Interception of an Unsymmetrical Isodihydropyridine","3-Bromo-1-methyl-1,2,5,6-tetrahydropyridine(N−B)borane (7) was prepared from 3-bromopyridine by conversion to 3-bromo-1-methylpyridinium iodide, hydrogenation of the latter with sodium tetrahydroborate and treatment of the resulting 3-bromo-1-methyl-1,2,5,6-tetrahydropyridine (6) with borane−dimethyl sulfide. Whereas no trapping product of the possible intermediate 1-methyl-1-azacyclohexa-2,3-diene (4) could be observed on treatment of 6 with potassium tert-butoxide in the presence of furan, the subjection of 7 to the same conditions produced the hexahydroepoxyquinoline derivatives 8a−c. Treatment of 7, dissolved in styrene, with sodium bis(trimethylsilyl)amide furnished the hexahydrocyclobutapyridine derivatives 9a−c. The six-membered cycloallene 1-methyl-1-azacyclohexa-2,3-diene(N−B)borane (10) must be regarded as the key intermediate en route to 8 and 9.",10.1002/1099-0690(200107)2001:14<2665::aid-ejoc2665>3.0.co;2-i,2001-07-01,0.5825906602469025
Journal of Organic Chemistry,Conformationally Constrained 7-Azabicyclo[2.2.1]heptane Amino Acids. Synthesis of a Glutamic Acid Analogue,"We report the synthesis of 2-substituted 7-azabicyclo[2.2.1]heptane glutamic acid analogue 27 from L-serine. Hemiaminal intermediate 2 can be converted to the 2S,3S,5S-trisubstituted pyrrolidine 3 by a tandem Wittig/Michael reaction or to the 2S,3S,5R-trisubstituted pyrrolidine 4 via an iodosulfonamidation reaction. The key transannular alkylation step to form the [2.2.1] ring system involves a beta-elimination of a silyl ether followed by cyclization to afford tert-butyl 7-benzyloxycarbonyl-7-azabicyclo[2.2.1]-2-heptene-1-carboxylate (20). Selective functionalization at C-2 was accomplished by the direct reduction with SmI(2) of 2-keto-3-silyl ether 23 to the C-2 ketone 24, which was converted to alpha,beta-unsaturated ester 25. Stereospecific reduction of the double bond from the exo face leads to a single protected glutamate analogue, tert-butyl (1S,2R,4R)-7-benzyloxycarbonyl-2-(methoxycarbonylmethyl)-7-azabicyclo[2.2.1]heptane-1-carboxylate (27).",10.1021/jo982327c,1999-02-25,0.5825891618396003
Angewandte Chemie International Edition,Total Synthesis of Clavosolide A via Asymmetric Alcohol‐Mediated Carbonyl Allylation: Beyond Protecting Groups or Chiral Auxiliaries in Polyketide Construction,"The 20-membered marine macrodiolide clavosolide A is prepared in 7 steps (LLS) in the absence of protecting groups or chiral auxiliaries via enantioselective alcohol-mediated carbonyl addition. In 9 prior total syntheses, 11-34 steps (LLS) were required.",10.1002/anie.201906259,2019-06-05,0.5825840023713578
Organic Letters,Synthesis of Amcenestrant (SAR439859): A Copper-Catalyzed Cross-Coupling Reaction as a Sustainable Alternative to Palladium-Catalyzed Suzuki Reaction,"A cross-coupling reaction between an enol triflate and an aryl Grignard reagent using a copper catalyst, followed by a deprotection step, a Mitsunobu reaction, and a saponification, allowed for the synthesis of Amcenestrant (SAR439859). This approach, avoiding an expensive and toxic transition metal, is as efficient as the classical route but less expensive for accessing this selective estrogen-receptor degrader (SERD).",10.1021/acs.orglett.5c00772,2025-03-07,0.5825788995488835
Tetrahedron,Metal-ammonia reduction and reductive alkylation of naphthalene sulphonamides. A new route to substituted naphthalenes.,,10.1016/s0040-4039(00)80526-2,1988-01-01,0.582577668833107
Journal of Organic Chemistry,Friedel−Crafts Acylation and Metalation Strategies in the Synthesis of Calothrixins A and B,The total syntheses of calothrixins A and B starting from readily available indole and the acid chloride 4 are described.,10.1021/jo035049c,2003-10-11,0.5825749405575616
Journal of the American Chemical Society,Synthesis of Potent Bicyclic Bisarylimidazole c-Jun N-Terminal Kinase Inhibitors by Catalytic C−H Bond Activation,"The efficient preparation of the privileged bicyclic bisarylimidazole kinase inhibitor scaffold was accomplished using rhodium-catalyzed C−H activation and intramolecular alkylation. The key C−H activation/alkylation step represents one of the first evaluations of diastereocontrol in catalyzed C−H activation/olefin alkylation processes. Several inhibitors of JNK3 were prepared using this sequence, with the most potent inhibitor having an IC 50 value of 1.6 nM.",10.1021/ja0676004,2006-12-23,0.5825748926293862
Synlett,Asymmetric Total Synthesis of (–)-trans-Blechnic Acid via Rhodium(II)-Catalyzed C–H Insertion and Palladium(II)-Catalyzed C–H Olefination Reactions,"An asymmetric total synthesis of (–)- trans -blechnic acid, a dihydrobenzofuran neolignan, has been achieved. The key steps involve an elaboration of the cis -2,3-dihydrobenzofuran core structure by enantio- and diastereoselective intramolecular C–H insertion using dirhodium(II) tetrakis[ N -phthaloyl-( R )- tert -leucinate] [Rh 2 ( R -PTTL) 4 ] and a direct coupling of an acrylate unit with the core structure employing Yu’s palladium(II)-catalyzed intermolecular C–H olefination.",10.1055/s-0033-1340291,2013-12-03,0.5825731333147232
Journal of Organic Chemistry,Synthesis of (+)-Vitepyrroloid A and (+)-Vitepyrroloid B by Late-Stage Ni-Catalyzed C(sp2)–C(sp3) Cross-Electrophile Coupling,"A concise and scalable five-step synthesis of vitepyrroloids A and B, two cytotoxic labdane diterpenoid alkaloids from Vitex trifolia, is reported. The presented approach features a Ni-catalyzed cross-electrophile coupling between a (+)-sclareolide-derived alkyl iodide and 3-bromo-2-cyanopyrrole.",10.1021/acs.joc.8b00882,2018-05-18,0.5825719033413002
Organic Letters,Controlling the Facial Selectivity of Asymmetric [4 + 2] Cyclo-additions: A Concise Synthesis of the <i>cis</i>-Decalin Core Structure of Superstolides A and B,"Regio-, stereo-, and facial selective [4 + 2] cycloadditions between highly activated vinyl sulfones and 1,3-dienes derived from (R)-4-tert-butyldimethylsilyloxy-2-cyclohexen-1-one provide a powerful approach for the asymmetric synthesis of compounds containing the bicyclo[2.2.2]octanone carbon skeleton. This new methodology has been successfully applied to the asymmetric synthesis of the cis-decalin core structure of the potent anticancer marine natural products superstolides A and B.",10.1021/ol201095b,2011-06-14,0.5825675401272928
Journal of Organic Chemistry,Asymmetric Hetero Diels−Alder as an Access to Carbacephams,"A short and efficient asymmetric synthesis of the (6R,7S)-7-tert-butoxycarbonylamino-2-ketocarbacepham is described. The key step involves the hetero Diels-Alder reaction of the benzylimine derived from the enantiomer of Garner's aldehyde with Danishefsky's diene.",10.1021/jo016186h,2001-12-22,0.5825588257827898
Tetrahedron,A stereoselective total synthesis of (±)-oppositol by a doubly diastereoselective intramolecular ester enolate alkylation,,10.1016/s0040-4039(96)02313-1,1997-01-01,0.582553761844894
European Journal of Organic Chemistry,"Synthesis of Naphtho[1,8‐ <i>bc</i> ]oxepines Through an HFIP‐Promoted <i>P</i> <i>eri</i> ‐Selective Arene–Epoxide Cyclization","We describe a hexafluoroisopropanol (HFIP)‐promoted epoxide ring‐opening cyclization of readily accessible 2‐[(2‐substituted‐1‐naphthyloxy)methyl]‐3‐aryloxiranes, proceeding via a regioselective 7‐ endo cyclization at the peri (C8) position of the naphthalene ring. This transformation provides a new class of naphtho[1,8‐ bc ]oxepine derivatives with complete regio‐ and diastereoselectivity. The C2 substituent on the naphthalene framework, along with the π ‐activating aryl group on the epoxide, plays a pivotal role in enabling the reaction. The method operates under mild conditions, tolerates a broad substrate scope, and is readily amenable to gram‐scale synthesis. Moreover, the versatility of this strategy is underscored by its successful extension to the diastereoselective synthesis of oxepino[4,3,2‐ cd ]indoles.",10.1002/ejoc.202501042,2025-12-09,0.582551540463461
Synthesis,"New Route to Unsymmetrical 9,10-Disubstituted Ethynylanthracene Derivatives","The preparation of new organic compounds bearing ethynylanthracene fragments is described, and an original pathway for the selective synthesis of unsymmetrical 9,10-diethynylanthracenes is given. The synthesis of some 9-ethynyl-10-substituted anthracene derivatives is also reported.",10.1055/s-2005-918512,2006-01-01,0.5825496109607649
Journal of the American Chemical Society,Total Synthesis of Swinholide A: An Exposition in Hydrogen-Mediated C–C Bond Formation,"Diverse hydrogen-mediated C-C couplings enable construction of the actin-binding marine polyketide swinholide A in only 15 steps (longest linear sequence), roughly half the steps required in two prior total syntheses. The redox-economy, chemo- and stereoselectivity embodied by this new class of C-C couplings are shown to evoke a step-change in efficiency.",10.1021/jacs.6b10645,2016-10-25,0.5825492870799883
Synthesis,"Remote Deprotometalation-Iodolysis of N,N-Diisopropyl-2-trimethylsilylferrocenecarboxamide: A New Route Toward 1,1′-Disubstituted Ferrocenes","The 1,1′-disubstitution is currently the most frequent substitution pattern encountered in the ferrocene series. Here an original access based on the remote deprotometalation of N,N-diisopropyl-2-trimethylsilylferrocenecarboxamide is reported. The key intermediate, 1′-iodo-N,N-diisopropylferrocenecarboxamide, was prepared in multiple grams and was further functionalized toward fifteen 1′-substituted iodoferrocenes.",10.1055/s-0040-1707175,2020-07-01,0.5825481248661326
Synlett,Novel Synthesis of Chiral Unactivated2-Aryl-1-benzylaziridines,"Chiral (RS,R)- and (RS,S)-N-(tert-butylsulfinyl)-2-aryl-aziridines were transformed into (R)- and (S)-2-aryl-1-benzylaziridines via a short three-step procedure. Deprotection and ring opening of (RS,R)- and (RS,S)-N-sulfinyl-2-arylaziridines (95-99% de) in acid medium afforded 2-aryl-2-chloroethylamine hydrochlorides in high yield (83-90%). These intermediates were converted into the corresponding chiral N-(benzylidene)-β-aryl-β-chloro-amines in good yield (78-85%). Subsequent reduction of the synthesized ald­imines afforded chiral 2-aryl-1-benzylaziridines in good to excellent yield (74-94%) and enantiomeric excess (83-99% ee). The enantiomeric purity of the chiral aldimines and aziridines was established by NMR spectroscopy using Pirkle alcohol as the chiral solvating agent.",10.1055/s-0028-1088125,2009-04-08,0.5825480338540258
European Journal of Organic Chemistry,"Pd-Catalyzed Asymmetric Allylic Alkylation of 3-Acetoxy-N-(tert-butyloxycarbonyl)-1,2,3,6-tetrahydropyridine – Preparation of Key Intermediates for Natural Product Synthesis","A convenient synthesis of racemic tetrahydropyridine 1 was developed. Pd-catalyzed allylic alkylation of 1 with malonate and dimethylacetoxymalonate as nucleophiles with the phosphanylcarboxylic acid L1 and the dihydrooxazol L2 as ligands, were carried out and gave enantiomeric excesses of up to 98%. Absolute configurations were determined for all compounds described. From the alkylation products (+)- and (–)-2a, and (+)- and (–)-2b a variety of versatile, nonracemic chiral intermediates were prepared.",10.1002/(sici)1099-0690(199910)1999:10<2515::aid-ejoc2515>3.0.co;2-g,1999-10-01,0.5825439011294078
European Journal of Organic Chemistry,"Pd-Catalyzed Asymmetric Allylic Alkylation of 3-Acetoxy-N-(tert-butyloxycarbonyl)-1,2,3,6-tetrahydropyridine – Preparation of Key Intermediates for Natural Product Synthesis","A convenient synthesis of racemic tetrahydropyridine 1 was developed. Pd-catalyzed allylic alkylation of 1 with malonate and dimethylacetoxymalonate as nucleophiles with the phosphanylcarboxylic acid L1 and the dihydrooxazol L2 as ligands, were carried out and gave enantiomeric excesses of up to 98%. Absolute configurations were determined for all compounds described. From the alkylation products (+)- and (–)-2a, and (+)- and (–)-2b a variety of versatile, nonracemic chiral intermediates were prepared.",10.1002/(sici)1099-0690(199910)1999:10<2515::aid-ejoc2515>3.3.co;2-7,1999-10-01,0.5825439011294078
Tetrahedron,"A regio and stereospecific radical annulation route to chiral tricyclo[4.3.1.o3,7]decane (isotwistane) system1 synthesis of (+)-10-α-Naphthyl-5-epi-Pupukean-9-one",,10.1016/0040-4039(91)80234-w,1991-11-01,0.5825429120080148
Synthesis,Intramolecular Addition of Hydroxy Group to a Diene System: Oxymercuration - Demercuration and Titanium Tetrachloride Catalyzed Synthesis of Manoyl Oxides,"All articles of this category The stereochemistry of the formation of tetrahydropyran ring of ent -manoyl oxides from ent -8α-hydroxylabda-13(16), 14-dienes has been studied in one and two-step oxymercuration-demercuration (OM-DM) processes as well as by a new titanium tetrachloride catalyzed cyclization which allows the preparation of this tetrahydropyran moiety of C-13 epimer manoyl oxides in high yield.",10.1055/s-1991-26468,1991-01-01,0.5825409772611404
Tetrahedron,A novel one-pot synthesis of receptor-type molecules containing two tetrathiafulvalene moieties,,10.1016/0040-4039(95)01713-r,1995-11-01,0.582538433478154
Tetrahedron,A Novel One-Pot Synthesis of Receptor-type Molecules Containing Two Tetrathiafulvalene Moieties,,10.1016/00404-0399(50)1713r-,1995-11-06,0.582538433478154
Green Chemistry,Synthesis of allylbenzenes,"A facile route for the synthesis of allylbenzenes is described from easily accessible allyl bromide and arylboronic acids using a new reusable catalyst system, palladium chloride and tetraphenylphosphonium bromide intercalated clay.",10.1039/a905846j,1999-01-01,0.5825372983627506
Angewandte Chemie International Edition,Selective Targeting of Tumor and Stromal Cells By a Nanocarrier System Displaying Lipidated Cathepsin B Inhibitor,"Cathepsin B (CtsB) is a lysosomal cysteine proteinase that is specifically translocated to the extracellular milieu during cancer progression. The development of a lipidated CtsB inhibitor incorporated into the envelope of a liposomal nanocarrier (LNC-NS-629) is described. Ex vivo and in vivo studies confirmed selective targeting and internalization of LNC-NS-629 by tumor and stromal cells, thus validating CtsB targeting as a highly promising approach to cancer diagnosis and treatment.",10.1002/anie.201402305,2014-06-27,0.5825337133218662
Synlett,Concise Synthesis of a Cyclopentane Intermediate Possessing All Nitrogen Functionalities for Pactamycin,"Pactamycin, a potent antitumor and antimicrobial antibiotic, possesses a densely functionalized cyclopentane core structure. This paper describes the concise synthesis of an advanced intermediate for synthesizing the enantiomer of pactamycin that contains the cyclopentane skeleton bearing all the necessary amino functions with correct stereochemistries.",10.1055/s-0036-1588495,2017-07-27,0.5825279692467636
Journal of the American Chemical Society,Total Synthesis and Structural Confirmation of the Marine Natural Product Dysinosin A:  A Novel Inhibitor of Thrombin and Factor VIIa,"The structure and absolute configuration of the marine antithrombotic product dysinosin A was confirmed by total synthesis. The strategy involved disconnections to three subunits, of which two were synthesized from the readily available l-glutamic acid, d-leucine, and d-mannitol. The Grubbs olefin metathesis carbocyclization reaction was utilized to prepare two intermediates.",10.1021/ja0208153,2002-10-17,0.5825256661180509
Journal of Organic Chemistry,Asymmetric Total Synthesis of Halicholactone,"The asymmetric total synthesis of the marine metabolite, halicholactone 1, is described. The bisallylic triol 6 with three chiral centers at C8, C12, and C15 was constructed by [2,3]-sigmatropic rearrangement of the sulfoxide 18, which was prepared stereoselectively using the chirality of (diene)Fe(CO)3 complexes. Introduction of the trans-substituted cyclopropane subunit into 21 was successfully achieved using the modified regio- and stereoselective Simmons-Smith reaction. The use of RCM (ring-closing metathesis) methodology (4-->35) was pivotal for the formation of a nine-membered unsaturated lactone fragment of halicholactone 1. As this approach is flexible and stereoselective, other oxylipins could be synthesized by the protocol described herein.",10.1021/jo001036c,2000-12-09,0.5825235608007587
Organic Process Research & Development,New Manufacturing Procedure of Cetirizine,"A new procedure for the manufacture of cetirizine dihydrochloride via the new intermediate 2-(2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethoxy)- N, N -dimethylacetamide dihydrochloride, synthesized by O-alkylation of 2-{4-[(4-chlorophenyl)(phenyl)methyl]piperazin-1-yl}ethanol with 2-chloro- N, N -dimethylacetamide, is elaborated. Hydrolysis of the resulting amide and subsequent salification provided cetirizine dihydrochloride.",10.1021/op300009y,2012-06-01,0.5825214265277939
Synlett,Synthesis of (±)-Homononactic Acid by Using cis-Selective Iodoetherification,All articles of this category (±)-Homononactic acid and its 8-epimer were synthesized by using cis -selective iodoetherification as the key step. (±)-homononactic acid - iodoetherification - tetranactin - tert -butyl ether,10.1055/s-1996-5536,1996-08-01,0.5825185993562815
Tetrahedron,Rapid and efficient isolation of the nicotinic receptor antagonist methyllycaconitine from delphinium: Assignment of the methylsuccinimide absolute stereochemistry as S,,10.1016/s0040-4039(00)78476-0,1994-11-01,0.5825170265714831
Journal of Organic Chemistry,First Synthesis of Caerulomycin C,"The first synthesis of caerulomycin C (1), an antibiotic produced by Streptomyces caeruleus, is reported. This molecule, which exhibits a 2,3,4,6-tetrasubstituted pyridine structure, was prepared from 3,4-dimethoxypyridine in a five-step sequence. The methodology involves metalation, transmetalation, aromatic cross-coupling, and halogen migration reactions.",10.1021/jo950823k,1996-01-01,0.5825153317058072
Journal of Organic Chemistry,Diastereoselective Synthesis of Substituted Tetrahydroquinoline-4-carboxylic Esters by a Tandem Reduction−Reductive Amination Reaction,"A diastereoselective synthesis of 1-methyl-2-alkyl- and 2-alkyl-1,2,3,4-tetrahydroquinoline-4-carboxylic esters has been developed from methyl (2-nitrophenyl)acetate (1). The method involves alkylation of 1 with an allylic halide, ozonolysis of the double bond, and catalytic hydrogenation. The final hydrogenation initiates a tandem sequence involving (1) reduction of the aromatic nitro group, (2) condensation of the aniline or hydroxylamine(8) nitrogen with the side chain carbonyl, (3) reduction of the resulting nitrogen intermediate, and (4) reductive amination of the tetrahydroquinoline with formaldehyde produced in the ozonolysis to give a methyl (+/-)-1-methyl-2-alkyl-1,2,3,4-tetrahydroquinoline-4-carboxylate. Removal of the formaldehyde prior to hydrogenation gives the simple (+/-)-2-alkyl derivatives. The products are isolated in high yield as single diastereomers having the C-2 alkyl group cis to the C-4 carboxylic ester. The reaction has been extended to the synthesis of tricyclic structures with similar high diastereoselection.",10.1021/jo001761n,2001-03-16,0.582509915423497
European Journal of Organic Chemistry,A Concise Synthesis of (–)‐ and (+)‐<i>trans</i>‐Whisky Lactones,"Abstract Concise enantioselective eleven‐step syntheses leading to(–)‐ and (+)‐ trans ‐whisky lactones were developed. Propargyl alcohol was employed as starting material. The reaction sequences include highly diastereoselective electrophilic cyclization of γ‐allenoic acids, dehydroiodination, and hydrogenation.",10.1002/ejoc.200901058,2009-12-18,0.5825074577923848
Synthesis,Eine neue Synthese von (<i>S</i>)-β-Methyl-γ-butyrolacton und (<i>S</i>)-4-Benzyloxy-3-methylbutansäure,"All articles of this category A New Synthesis of ( S )-β-Methyl-γ-butyrolactone and ( S )-4-Benzyloxy-3-methylbutanoic Acid A stereoselective synthesis of ( S )-β-methyl-γ-butyrolactone [( S )-4,5-dihydro-4-methyl-2(3 H )-furanone, 1 ] and of ( S )-4-benzyloxy-3-methylbutanoic acid ( 2 ) is described. Both compounds are prepared starting from inexpensive L-ethyl lactate with overall yields of 26% and 30%, respectively. The products are valuable chiral building blocks.",10.1055/s-1991-26584,1991-01-01,0.5825057995360339
Chemical Science,"Intramolecular asymmetric reductive amination: synthesis of enantioenriched dibenz[ <i>c</i> , <i>e</i> ]azepines","]azepines featuring a broad substrate scope, and their synthetic utilities are exhibited by derivatizing the products into a chiral amino acid derivative and chiral phosphoramidite ligands, which display excellent enantiocontrol in Rh-catalyzed asymmetric hydrogenation of α-dehydroamino acid derivatives. Remarkably, our method is also applicable to enantioselectively synthesize an allocolchicine analogue.",10.1039/c8sc04482a,2018-12-27,0.5825049648209468
Organic Letters,"Controllable Si–C Bond Formation from Trihydrosilanes En Route to Synthesis of 1,4-Azasilinanes with Diverse Silyl Functionalities","A B(C 6 F 5 ) 3 -catalyzed controllable inter/intra-/intermolecular Si–C bond formation process has been developed from trihydrosilane and dienamide with alkenes, anilines, or aryl iodides. A variety of 1,4-azasilinanes have been generated with diverse exo -cyclic heteroleptic disubstitutions on silicon, thereby expanding the range of silaazacyclic rings available for the discovery of silicon-containing drugs.",10.1021/acs.orglett.3c03014,2023-10-04,0.5825008544931167
Organic Letters,"Stereoselective 6π-Electron Electrocyclic Ring Closures of 2-Halo-Amidotrienes via a Remote 1,6-Asymmetric Induction","A diastereoselective 6π-electrocyclic ring closure employing halogen-substituted 3-amidotrienes via a 1,6-remote asymmetric induction is described. This new asymmetric manifold for pericyclic ring closure further underscores the significance of the allenamide chemistry.",10.1021/ol102693e,2010-11-19,0.5824973302525162
Synlett,"Stereoselective Synthesis of Orthogonally Protected 1,2-Diaminoinositols from d-Mannose","We present herein a promising novel strategy for the transformation of sugar aldehydes into 1,2-diaminoinositols. This process, based on the sequential intermolecular aza-Henry reaction and intermolecular Henry reaction allowed the total synthesis of a 1,2-diaminoinositols with total stereochemical control. The new route constitutes a simpler and more efficient approach than those previously described routes to 1,2-diaminoinositols and it has the additional advantage of offering the possibility of orthogonal protection of the amino groups.",10.1055/s-0034-1378545,2014-08-06,0.5824969519011346
Angewandte Chemie International Edition,Total Synthesis of 1‐Hydroxytaxinine,"Abstract 1‐Hydroxytaxinine ( 1 ) is a cytotoxic taxane diterpenoid. Its central eight‐membered B‐ring possesses four oxygen‐functionalized centers (C1, C2, C9, and C10) and two quaternary carbon centers (C8 and C15), and is fused with six‐membered A‐ and C‐rings. The densely functionalized and intricately fused structure of 1 makes it a highly challenging synthetic target. Reported here is an efficient radical‐based strategy for assembling 1 from A‐ and C‐ring fragments. The A‐ring bearing an α‐alkoxyacyl telluride moiety underwent intermolecular coupling with the C‐ring fragment by a Et 3 B/O 2 ‐promoted decarbonylative radical formation. After construction of the C8‐quaternary stereocenter, a pinacol coupling reaction using a low‐valent titanium reagent formed the B‐ring with stereoselective installation of the C1,C2‐diol. Subsequent manipulations at the A‐ and C‐rings furnished 1 in 26 total steps.",10.1002/anie.201906872,2019-06-18,0.58249194591545
Journal of Organic Chemistry,Phenolic Dienes as Highly Selective Dienophiles in the Asymmetric Organocatalyzed Three-Component Vinylogous Povarov Reaction,"Our study presents a novel enantioselective route for the synthesis of 1,2,3,4-tetrahydroquinolines via a chiral phosphoric acid-catalyzed three-component Povarov reaction, employing phenolic dienes as dienophiles. This approach produces a diverse array of 2,3,4-trisubstituted tetrahydroquinolines, each featuring a styryl group at position 4, in high yields with excellent regio-, diastereo-, and enantioselectivities (>95:5 dr and up to >99% ee).",10.1021/acs.joc.4c01239,2024-08-17,0.5824914666242396
Journal of Organic Chemistry,Total Synthesis of Chalaniline A: An Aminofulvene Fused Chromone from Vorinostat-Treated Fungus <i>Chalara</i> sp. 6661,"Chalaniline A, an aminofulveno[1,2- b ]chromone derivative previously isolated from a vorinostat-treated ascomycete Chalara sp., was prepared in nine steps from orcinol (3,5-dihydroxytoluene). In a key transformation, the tricyclic ring system of the target was generated by a pyrrolidine-catalyzed double annulation between α-(methylsulfinyl)-2,6-dihydroxy-4-methylacetophenone and the ketaldoester, methyl 2,5-dioxopentanoate. The resulting tertiary alcohol (coniochaetone H) was further converted to chalaniline A by operations including dehydration (to yield a hydroxyfulvene), Vilsmeier reaction, and enamine exchange.",10.1021/acs.joc.4c01855,2024-09-23,0.5824830752399625
Tetrahedron,Carbocyclization by homolytic substitution (SH′ process). A new route to dihydroindole or dihydrobenzofuran,,10.1016/s0040-4039(00)87399-2,1982-01-01,0.5824808308068747
Organic Process Research & Development,"The Synthesis of the High-Potency Sweetener, NC-00637. Part 2:  Preparation of the Pyridine Moiety","The pyridine moiety within the high-potency sweetener, NC-00637 ( 1 ), 5-amino-2-cyanopyridine ( 4 ), was prepared from 2-hydroxy-5-nitropyridine ( 10 ). The sequence involved the conversion of the hydroxy group to bromide followed by substitution with cyanide to give 2-cyano-5-nitropyridine ( 8 ). Reduction of the nitro group proved to be troublesome when catalytic hydrogenation was used. Iron with an acid gave a reproducible reaction that could be used at scale.",10.1021/op034110c,2003-12-04,0.5824747672999967
Tetrahedron,A new asymmetric synthesis of (+)-grandisol via a kinetic resolution,,10.1016/s0040-4039(99)01605-6,1999-10-01,0.5824739132854285
Journal of Organic Chemistry,Organocatalytic and Late-Stage CH-Functionalization Enabled Asymmetric Synthesis of Communesin F and Putative Communesins,"Herein we report the total syntheses of communesin F and putative members of the communesin family of polycyclic bis-aminal alkaloids. The successful strategy featured a novel organocatalytic reaction between two oxindole subunits to cast, after extensive optimization, the all-carbon vicinal quaternary stereocenters of the target molecule with high enantiocontrol. The resulting bis-oxindole intermediate further underwent a Ti(O i Pr) 4 -mediated dehydrative skeletal rearrangement to furnish the communesin core structure. Consider the ready availability and low-cost of unsubstituted isatin, and the inferior organocatalytic reaction employing a bromo-substituted substrate, a Pd(OAc) 2 -catalyzed and oxalamide-directed aryl CH-alkenylation reaction was implemented to assemble the complete skeletal backbone of the target molecule. Collectively, the synthetic technologies disclosed herein constitute the first asymmetric organocatalytic approach to the communesins, together with a highly effective late-stage CH-functionalization in stark contrast to the bromoarene substrates employed in all of the past synthetic work.",10.1021/acs.joc.7b02426,2017-11-01,0.5824736641614868
Tetrahedron,The reactions of activated amides. Part (II). A new synthetic route to ββ-disubstituted indoline derivateves.,,10.1016/s0040-4039(01)98791-x,1968-01-01,0.5824643578834383
European Journal of Organic Chemistry,Expedient Pd‐Catalyzed α‐Arylation towards Dibenzoxepinones: Pivotal Manske's Ketone for the Formal Synthesis of Cularine Alkaloids,"The general synthesis of diversely substituted dibenzoxepinones by a combined Pd‐catalyzed α‐arylation and S N Ar strategy is reported and applied to the synthesis of Manske's ketone, a key intermediate en route to the total synthesis of cularine alkaloids. In the course of this work, an unanticipated ring contraction reaction to a xanthone was observed and serves as a caveat for the conditions of the widely used α‐arylation reaction.",10.1002/ejoc.202000424,2020-04-03,0.5824628893529358
Synthesis,A Regioselective Route to 5-Substituted Isoxazole- and Isoxazoline-3-phosphonates,"5-Substituted 3-(diethoxyphosphoryl)isoxazoles and -2-isoxazolines were synthesized regioselectively by 1,3-dipolar cycloaddition of (diethoxyphosphoryl)formonitrile oxide to monosubstituted alkynes and alkenes. By applying this methodology to an N-(tert-butoxycarbonyl)-substituted allylglycine methyl ester, we prepared the precursors of two diastereomeric 3-phosphono-2-isoxazolin-5-yl-substituted amino acids, which are bioisosteres of potent NMDA receptor antagonists.",10.1055/s-0028-1083343,2009-01-27,0.5824608648053656
Journal of Organic Chemistry,"A Raney-Cobalt-Mediated Tandem Reductive Cyclization Route to the 1,5-Methanoazocino[4,3-<i>b</i>]indole Framework of the Uleine and <i>Strychnos</i> Alkaloids","The readily accessible enones 8, 17, and 18 undergo 2-fold reductive cyclization reactions upon exposure to hydrogen in the presence of Raney-cobalt and thereby afford compounds 11 (72%), 19 (47%), and 20 (84%), respectively. These products embody the ABCD-ring system associated with the title alkaloids, and compound 11 can be converted, over four steps and in 33% yield, into congener 24 incorporating the ABCDE-ring system of the Strychnos alkaloids.",10.1021/jo302132d,2012-10-24,0.5824596268850709
Angewandte Chemie International Edition,"Utilizing an <i>o</i>‐Quinone Methide in Asymmetric Transfer Hydrogenation: Enantioselective Synthesis of Brosimine A, Brosimine B, and Brosimacutin L","A concise and highly enantioselective synthesis of the flavonoids brosimine A, brosimine B, and brosimacutin L is reported for the first time. The key transformation is a single-step conversion of a flavanone into a flavan by means of an asymmetric transfer hydrogenation/deoxygenation cascade.",10.1002/anie.201507269,2015-12-04,0.5824592013698551
Angewandte Chemie International Edition,Total Synthesis of Apoptolidin: Part 2. Coupling of Key Building Blocks and Completion of the Synthesis,"No less than 30 stereogenic elements, a highly unsaturated 20-membered macrocyclic system, four carbohydrate units, and unique biological activity, make the natural occurring apoptolidin (1) a challenging synthetic target. The retrosynthetic analysis revealed five key building blocks-three for the construction of the macrolide ring B and two prospective pendant saccharide units-which were synthesized in a highly convergent manner and then connected. Apoptolidin's rather labile nature proved particularly challenging in the final deprotection, purification, and characterization procedures.",10.1002/1521-3773(20011015)40:20<3854::aid-anie3854>3.0.co;2-d,2001-10-15,0.5824574192466632
Angewandte Chemie International Edition,Total Synthesis of (+)‐Kalmanol,"Kalmanol, the flagship member of the kalmane diterpene family, possesses a complex and highly oxidized 5/5/8/5 tetracyclic skeleton with nine contiguous stereocenters and exhibits significant analgesic effects and cardiotoxic properties. We have achieved the efficient total synthesis of (+)-kalmanol in 22 steps with 2.3 % yield. The synthesis featured a Rh-catalyzed [5+2+1] cycloaddition reaction to construct 5/5/8 tricyclic skeleton, and a meticulously designed sequence of stereoselective oxidations of the 5/5/8/5 tetracyclic skeleton.",10.1002/anie.202407215,2024-07-31,0.5824572410278489
Organic Letters,"Lituarine Synthetic Studies. An Efficient, Stereocontrolled Construction of the Common C(7−19) Tricyclic Spiroketal Fragment","A highly efficient, stereocontrolled synthesis of (+)-4, the common C(7-19) tricyclic spiroketal fragment of the lituarines A, B, and C (1-3), has been achieved. Highlights of the synthesis include a remarkably facile 6-endo cyclization to access the C(8-12) pyran ring and a kinetically controlled acid-catalyzed spiroketalization. [reaction: see text]",10.1021/ol016948v,2001-11-01,0.5824564219063975
Angewandte Chemie International Edition,Asymmetric Synthesis of β‐Ketoamides by Sulfonium Rearrangement,"The synthesis of enantioenriched α-substituted 1,3-dicarbonyls remains a contemporary challenge in synthesis due to their tendency to undergo racemization via keto-enol tautomerization. Herein, we report a method to access enantioenriched β-ketoamides by a chiral sulfinimine-mediated [3,3]-sigmatropic sulfonium rearrangement. The transformation displays good chirality transfer, as well as excellent chemoselectivity and functional group tolerance. Diastereoselective reduction of the ketone moiety, also achievable in one-pot fashion, affords enantioenriched β-hydroxyamides.",10.1002/anie.202418070,2024-10-23,0.5824562188664137
Synthesis,Iminophosphorane-Mediated Synthesis of the Alkaloid Cryptotackieine,"(opens in new window) Buy Article (opens in new window) Permissions and Reprints (opens in new window) All articles of this category (opens in new window) A new synthesis of the alkaloid cryptotackieine based on the stepwise formation of the pyridine and indole ring is described. The key step, formation of the appropriate 3-arylquinoline, involves a Staudinger/aza-Wittig/electrocyclic ring-closure process. Staudinger reaction - aza-Wittig reaction - electrocyclic ring-closure - cryptotackieine - microwave-promoted methylation",10.1055/s-1999-3386,1999-02-01,0.5824503732416079
Tetrahedron,A short and efficient synthesis of enantiopure (+)-N-Boc-7-azabicyclo[2.2.1]heptan-2-one utilizing an asymmetric desymmetrization protocol: formal total synthesis of (−)-epibatidine,,10.1016/s0040-4039(01)00616-5,2001-06-01,0.5824496311042803
Tetrahedron,A novel synthesis of 4-hydroxymethyl-2-phenylthiazole involving an epoxy-2-thiazoline intermediate,,10.1016/s0040-4039(01)88271-x,1969-01-01,0.5824482809186967
Tetrahedron,"The synthesis of 6-amino-4-methyl-8-(β-D-ribofuranosyl) (4-H,8-H)pyrrolo-[4,3,2-de]pyrimido[4,5-c]pyridazine, a new tricyclic nucleoside",,10.1016/s0040-4039(01)87546-8,1971-01-01,0.5824473427532272
Tetrahedron,Prostaglandin VI - an efficient synthesis of II-desoxyprostaglandins,,10.1016/s0040-4039(01)95833-2,1973-01-01,0.5824436803522752
Chemical Science,Correction: Synergistic formal ring contraction for the enantioselective synthesis of spiropyrazolones,"Correction for ‘Synergistic formal ring contraction for the enantioselective synthesis of spiropyrazolones’ by Marta Meazza <italic>et al.</italic> , <italic>Chem. Sci.</italic> , 2018, <bold>9</bold> , 6368–6373.",10.1039/c9sc90160d,2019-01-01,0.582434786634343
Synthesis,"Regiocontrolled SNAr Reaction on 2,3-Dihalopyridines with NaSMe To Obtain Bromo(methylthio)pyridines as Key Precursors of 3-Halo-2-(hetero)arylthieno[2,3-b]pyridines and Thieno[3,2-b]pyridines","The synthesis of 3-halo-2-(hetero)arylthieno[2,3- b ]pyridines and 3-halo-2-(hetero)arylthieno[3,2- b ]pyridines has been performed through a three-step methodology from 3-bromo-2-chloropyridine or 2-bromo-3-fluoropyridine, respectively. The key step of this methodology is the formation of the required bro­mo(methylthio)pyridines by a regiocontrolled nucleophilic aromatic substitution (S N Ar) with sodium methanethiolate (NaSMe). Then, the Sonogashira coupling with (hetero)arylalkynes followed by a halocyclization with bromine or iodine, afforded the expected 3-halo-2-(hetero)arylthienopyridines.",10.1055/s-0033-1338442,2013-05-08,0.5824263189768901
Synlett,Synthetic Studies towards the Total Synthesis of Indole Alkaloids Containing Indolyl Lactam Frameworks,"Abstract In this account, recent progress on the synthetic studies of several monoterpene indole alkaloids, (±)-mersicarpine, misassigned (±)-tronoharine, and (±)-leuconodines D and E, is summarized. Specifically, the rationale for the design and development of the Lewis acid catalyzed SN1-type substitution and formal [3+3] cycloaddition reaction of indol-2-yl carbinols, and the Pd-catalyzed aerobic oxidative intramolecular Heck cross-coupling of indolyl amides tethered with a terminal olefin functionality, are emphasized. These key reactions set the basis for the rapid construction of the fused ring skeleton containing an all-carbon quaternary center at the indol-2-yl position. 1 Introduction 2 Synthetic Study of (±)-Mersicarpine 3 Synthetic Study of the Misassigned (±)-Tronoharine 4 Study of the Asymmetric Reaction of Indol-2-yl Carbinols 5 Synthetic Study of (±)-Leuconodines D and E 6 Conclusion",10.1055/s-0040-1706480,2020-10-07,0.582425268180926
Journal of the American Chemical Society,Organocatalytic Asymmetric Transferhydrogenation of β-Nitroacrylates: Accessing β<sup>2</sup>-Amino Acids,We describe a highly efficient and enantioselective Hantzsch ester mediated conjugate reduction of beta-nitroacrylates that is catalyzed by a Jacobsen thiourea catalyst as a key step in a new route to optically active beta2-amino acids.,10.1021/ja8069852,2008-09-25,0.5824201323587755
Organic Letters,<i>Ex Situ</i> Generation of Difluorodiazoethane (CF<sub>2</sub>HCHN<sub>2</sub>): Application in the Regioselective Synthesis of CF<sub>2</sub>H-Containing Pyrazoles,"A new method for the ex situ generation of difluorodiazoethane (CF 2 HCHN 2 ) and a procedure for its efficient use in [3 + 2] cycloaddition with nitroolefins by the AcOH/O 2 catalyst system were developed by using a simple two-chamber system. The method provides a facile and straightforward access to a series of 4-substituted 5-difluoromethyl-3-nitro-1 H -pyrazoles that are of interest in medicinal chemistry. Interestingly, the key factor for the success of this method is the efficient preparation of CF 2 HCHN 2 by an ex situ process.",10.1021/acs.orglett.9b03371,2019-10-23,0.5824190783595593
Synthesis,"One-Pot Synthesis of Tetrakis(alkylthio)ethylenes and of 1,3-Dithiole Derivatives from Bis(methylthio)methane","All articles of this category A new synthesis of tetrakis(alkylthio)ethylenes and of 1,3-dithiole derivatives is reported. The carbanion derived from bis(methylthio)methane is reacted with carbon disulfide, followed by alkylation and/or cyclization steps.",10.1055/s-1988-27570,1988-01-01,0.582413244443514
Journal of Organic Chemistry,Asymmetric Approach to Hyacinthacines B<sub>1</sub> and B<sub>2</sub>,"Naturally occurring hyacinthacines B1 and B2 have been prepared from a common, easily available, advanced intermediate. The approach features several highly stereoselective transformations: inter alia, a dichloroketene-enol ether [2 + 2] cycloaddition, a Bruylants alkylation, and an amino-nitrile alkylation-reduction.",10.1021/jo400386f,2013-04-04,0.5824107722339251
Tetrahedron,"Synthesis of a biologically active D-ring diolepoxide of the potent carcinogen 7,12-dimethylbenz[a]anthracene ()†",,10.1016/s0040-4039(01)83285-8,1977-01-01,0.5824100389207556
Tetrahedron,Development of a practical biocatalytic process for ( S )- N -Boc-3-hydroxypiperidine synthesis,,10.1016/j.tetlet.2017.03.037,2017-03-11,0.5824091352001481
Journal of Organic Chemistry,"New synthesis of pyrrolo [3,2,1-ij] quinolin-4-one derivatives","A new convenient synthesis of pyrrolo[3,2,1-ij]quinolin-4-one derivatives is described. In this method, methyl-7-hydroxquinoline-2-ones are the starting materials onto which the third pyrrolo ring is condensed directly, yielding dehydrogenated methyl-9-hydroxypyrrolo[3,2,1-ij]quinolin-4-ones.",10.1021/jo00003a016,1991-02-01,0.582407209369807
European Journal of Organic Chemistry,Synthesis of an Acyclic C1–C11 Fragment of Peloruside B,"Abstract The synthesis of a C1 reduced form of the C1–C11 fragment of peloruside B has been achieved in 15 synthetic steps. The strategy involved the use of D ‐tartaric acid to set the absolute stereochemistry and a 1,5‐ anti Mukiayama aldol reaction. Analog synthesis of C8–C11 is also reported, which enables changes at the C10 position of peloruside B to be made. The synthesis of the fragment concludes with C1 in the protected alcohol state rather than the natural ester.",10.1002/ejoc.201100053,2011-06-17,0.5824052637541705
Tetrahedron,One-step construction of a 13α-methyl 14α-hydroxy steroid via a new anionic polycyclization method,,10.1016/s0040-4039(00)82257-1,1988-01-01,0.5824013308683956
Tetrahedron,Synthesis of p38 MAP kinase inhibitor BIRB 796 and analogs via copper-mediated N-arylation reaction,,10.1016/j.tetlet.2010.06.109,2010-07-02,0.5823978628015377
Tetrahedron,"Asymmetric synthesis of ()-(+)-ethylmethyl--propylcarbinol in high enantiomeric purity. A 1,3-oxathiane derived from (+)-pulegone as chiral adjuvant",,10.1016/s0040-4039(01)81768-8,1981-01-01,0.5823970832708786
Organic Letters,Palladium-Catalyzed Reductive and Redox-Neutral Cyclization Approach to the Southern Core of Avermectins,"The avermectins make up a biologically relevant class of complex natural products that continue to inspire the development of new strategies in chemical synthesis. Herein, we disclose a concise synthesis of the southern core of avermectin aglycon. The key hydrobenzofuran was forged by either reductive cyclization or cycloisomerization, both using a cationic palladium precatalyst. This hydropalladation strategy generated the hydrofuran ring under mild conditions, enabling the rapid construction of the tetra-substituted carbon stereocenter.",10.1021/acs.orglett.4c04282,2024-12-18,0.5823877571735581
Angewandte Chemie International Edition,Concise Asymmetric Syntheses of Streptazone A and Abikoviromycin**,"Abstract Streptazone A and abikoviromycin are alkaloids that both feature an unusual arrangement of reactive functionalities within a compact tricyclic ring system. Here, we report a highly concise asymmetric synthesis of both natural products. The route first constructs another family member, streptazone B 1 , using a rhodium‐catalyzed distal selective allene‐ynamide Pauson–Khand reaction. A regio‐ and enantioselective epoxidation under chiral phase‐transfer catalytic conditions directly afforded streptazone A in 8 steps overall. In one additional step, a chemoselective, iridium‐catalyzed reduction of the enaminone system then gave abikoviromycin. The reactivity of streptazone A towards a cysteine mimic, N ‐acetylcysteamine, was studied and revealed unanticipated transformations, including bis‐thiol conjugation which may proceed via formation of a cyclopentadienone intermediate. With flexible access to these compounds, studies aimed to identify their direct biological targets are now possible.",10.1002/anie.202101439,2021-02-11,0.5823836096991928
Angewandte Chemie International Edition,Enantioselective Intramolecular α‐Arylation of Benzylamine Derivatives: Synthesis of a Precursor to Levocetirizine,"A practical, transition metal-free method allows the enantioselective synthesis of α,α-diarylmethylamines by asymmetric α-arylation of benzylamines. Enantioselective lithiation of N'-aryl-N-benzyl-N-isopropyl ureas using a chiral lithium amide base generates a benzyllithium that undergoes an unactivated stereospecific intramolecular nucleophilic aromatic substitution to generate an α,α-diarylmethylamine in the form of its urea derivative, in up to >99 % ee. Treatment with acid induces an ""azatropic shift"" with retention of configuration, the product of which may be hydrolysed to the target amine.",10.1002/anie.202216758,2023-01-26,0.582383517522911
Organic Letters,Total Synthesis of Siphonazoles by the Use of a Conjunctive Oxazole Building Block,"The preparation of 4-carbethoxy-5-methyl-2-(phenylsulfonyl)methyloxazole and its use in the elaboration of more complex oxazoles are described. A total synthesis of the unique natural products, siphonazoles A and B, illustrates an application of the new building block.",10.1021/ol900455m,2009-04-27,0.5823820061275037
Tetrahedron,Stereoselective total synthesis of (−)-galantinic acid and 1-deoxy-5-hydroxysphingolipids via prins cyclization,,10.1016/j.tetlet.2020.152149,2020-06-16,0.5823717687780562
Tetrahedron,One step facile synthesis of bromo calix[n]arenes,,10.1016/s0040-4039(02)01548-4,2002-09-01,0.5823691936120491
Synthesis,Improved Synthesis of Monohalogenated Cavitands and Their Use in the Synthesis of Further Functionalized Cavitands,"A new procedure for the synthesis of monohalogenated cavitands was established, which is at least one step shorter and far more atom-efficient than previously published pathways. These monohalogenated cavitands were demonstrated to be versatile synthons for the synthesis of further functionalized derivatives through cyanation, carboxylation, and a series of palladium-catalyzed Suzuki reactions.",10.1055/s-2006-926274,2006-01-01,0.5823664138490856
Synlett,Formal Total Synthesis of Clausenamide,"All articles of this category Ruthenium tetroxide oxidation of trans -5-substituted 4-acylaminocyclohexenes 2 followed by esterification gave N -protected cis -4-substituted 5-(methoxycarbonylmethyl)-2-pyrrolidones 4 . The resulting pyrrolidone 4a ( N -Boc-4-phenyl) was converted into the key intermediate 8 ( cis -5-formal-1-methyl-4-phenyl-2-pyrrolidinone), thus achieving the formal total synthesis of clausenamide [3-hydroxy-5-(α-hydroxybenzyl)-1-methyl-4-phenyl-2-pyrrolidinone].",10.1055/s-1991-34738,1991-01-01,0.5823645570655662
Tetrahedron,"Chiral bicyclic lactams. An asymmetric synthesis of cis-(1s, 3r) deltamethrinic acid",,10.1016/s0040-4039(00)99569-8,1989-01-01,0.5823622722828841
Journal of the American Chemical Society,Development of a Concise Synthesis of Ouabagenin and Hydroxylated Corticosteroid Analogues,"The natural product ouabagenin is a complex cardiotonic steroid with a highly oxygenated skeleton. This full account describes the development of a concise synthesis of ouabagenin, including the evolution of synthetic strategy to access hydroxylation at the C19 position of a steroid skeleton. In addition, approaches to install the requisite butenolide moiety at the C17 position are discussed. Lastly, methodology developed in this synthesis has been applied in the generation of novel analogues of corticosteroid drugs bearing a hydroxyl group at the C19 position.",10.1021/ja512022r,2015-01-16,0.5823622291152304
Angewandte Chemie International Edition,"Asymmetric Synthesis of Chiral 1,3‐Diaminopropanols: Bisoxazolidine‐Catalyzed CC Bond Formation with α‐Keto Amides","Three high-yielding steps lead to the formation of chiral 1,3-diaminopropanols from aliphatic and aromatic α-keto amides. In this approach, a nitroaldol reaction, which is catalyzed by Cu(SO2CF3)2 and the bisoxazolidine ligand L1, is followed by two mild reduction reactions (see scheme). Laborious protection and deprotection steps can be avoided by using this method.",10.1002/anie.201105778,2011-10-31,0.5823613235750802
Synthesis,Phenylthioacetylene,"All articles of this category A two-step synthesis of phenylthioacetylene from thiophenol and methoxymethylene Meldrum's acid (2,2-dimethyl-1,3-dioxane-4,6-dione) is described.",10.1055/s-1993-25997,1993-01-01,0.582355065702192
Synlett,Synthesis of Dibenzo-Fused Seven-Membered Heterocycles via Copper-Catalyzed Cyclization of 2-Haloaniline Compounds,"A one-step synthesis of dibenzo-fused seven-membered nitrogen heterocycles from acetophenones/benzophenones and 2-haloanilines, via a copper-catalyzed amination, was developed. The reaction involves animation followed by intramolecular cyclization.",10.1055/s-2008-1032055,2008-02-01,0.5823534027158355
Journal of Organic Chemistry,General Approach to Glycosidase Inhibitors. Enantioselective Synthesis of Deoxymannojirimycin and Swainsonine,"[reaction: see text] Deoxymannojirimycin (2) and swainsonine (4) have been synthesized from each enantiomer of the same bicyclic carbamate precursor 7. The key intermediate was prepared by a simple and efficient three-step synthesis involving RCM of the diene 8, which in turn is easily accessible in any configuration from enantiomerically enriched 2,3-epoxy-4-penten-1-ol 9.",10.1021/jo048172s,2005-02-17,0.5823440281273874
Tetrahedron,Stereocontrolled approach to trichothecane derivatives tricarbonylcyclo-hexadieneiron complexes: synthesis of a key intermediate.,,10.1016/0040-4039(80)80095-5,1980-01-01,0.582343165541728
Organic Letters,Total Synthesis of (±)-11-<i>O</i>-Debenzoyltashironin via Palladium-Catalyzed 5-<i>endo</i> Ene-yne Cyclization Enabled <i>trans</i>-5–6 Ring Fusion,"Illicium sesquiterpenes are a synthetically fascinating family of polycyclic natural products owing to their diversified pharmacological activities and structural complexity. Our cumulative efforts on developing a universal reductive coupling strategy toward stereoselective assembly of illicium sesquiterpenes recently resulted in a total synthesis of 11- O -debenzoyltashironin, a rare illicium sesquiterpene with a unique allo -cedrane carbon skeleton exhibiting prominent neurotropic activity, with complete stereochemical control. Our key tactics involved an unprecedented Pd(II)-catalyzed 5- endo ene-yne cyclization that directly allowed strained trans -5–6 ring fusion and a late-stage transannular McMurry coupling that furnished the compacted tetracyclic carbon skeleton rapidly.",10.1021/acs.orglett.0c00689,2020-03-19,0.5823424074707202
Journal of Organic Chemistry,α-Carbonyl Radical Cyclization Approach toward Angular Triquinanes:  Total Synthesis of Enantiomerically Pure (−)-5-Oxosilphiperfol-6-ene,"An alpha-carbonyl radical cyclization approach toward synthesis of angular triquinanes is described. As a model study, conjugate addition of 4-(trimethylsilyl)-3-butynylmagnesium chloride to enone 7 followed by trapping of the enolate with chlorotrimethylsilane gave trimethysilyl enol ether 8. Iodination of 8 with a mixture of NaI and m-CPBA afforded iodo ketone 6. Radical cyclization of 6 effected by Bu(3)SnH and AIBN gave 5. Epoxidation of 5 with m-CPBA yielded epoxy ketone 9. Desilylation and rearrangement of 9 by formic acid gave aldehyde 4. Aldol condensation and dehydration furnished angular triquinane skeleton 3. Total synthesis of (-)-5-oxosilphiperfol-6-ene (1) was accomplished in 12 steps starting from keto ester 14 based on this route. Conjugate addition of 3-hexynylmagnesium bromide to chiral ester 13 followed by treatment with chlorotrimethylsilane gave intermediate 15. Iodination of 15 with a mixture of NaI and m-CPBA gave alpha-iodo ester 12. Intramolecular radical cyclization of 12 gave ester 11. Reduction of 11 by LiAlH(4) yielded alcohol 16. On treatment with m-CPBA, alcohol 16 was converted to the corresponding epoxide 17, which was subjected to the epoxy-ketone rearrangement using BF(3) etherate as a catalyst to give ethyl ketone 18. Subsequent oxidation of 18 with PCC afforded aldehyde 10. Intramolecular aldol condensation of 10 yielded tricyclic compound 19. Methylation of 19 gave 20. Conjugate addition of lithium dimethylcuprate to 20 followed by trapping of the resulting enolate with chlorotrimethylsilane gave 21. Oxidation of 21 by DDQ afforded enantiomerically pure (-)-5-oxosilphiperfol-6-ene (1). Racemic (+/-)-1was also synthesized in the same manner in order to determine the optical purity of chiral product (-)-1. The gas chromatographic analysis with a chiral column proved that 1 has high enantiomeric purity. A single-crystal X-ray analysis of 2,4-dinitrophenylhydrazone 22 was performed to unambiguously confirm the stereochemistry of 19.",10.1021/jo9723570,1998-03-25,0.582341368270169
Organic Letters,"Approach to the Synthesis of Cladiell-11-ene-3,6,7-triol","[reaction: see text] The synthesis of an advanced intermediate in the synthesis of the title compound has been achieved. Key steps include an Ireland-Claisen rearrangement to install the C7 tertiary alcohol stereocenter, an SN2' reaction of an alkoxymethyl Cu reagent, and a diastereoselective Re-catalyzed allylic alcohol transposition.",10.1021/ol061072j,2006-07-29,0.5823360249781281
Organic Letters,Asymmetric Total Synthesis of (+)-Majusculoic Acid via a Dimerization–Dedimerization Strategy and Absolute Configuration Assignment,"The first total synthesis of (+)-majusculoic acid, the enantiomer of naturally occurring antifungal cyclopropane fatty acid (-)-majusculoic acid, was accomplished in 13 steps, leading to the assignment of the absolute configuration of the natural product. The synthesis featured a ring closing metathesis dimerization, a conformationally controlled cyclopropanation, a dedimerization, and a bromoolefination.",10.1021/acs.orglett.8b00349,2018-02-15,0.5823338654823905
Tetrahedron,Efficient generation and [3+2] cycloaddition of cyclic azomethine ylides: A general synthetic route to x-azabicyclo (m.2.1) alkane framework,,10.1016/s0040-4039(00)79314-2,1993-11-01,0.5823327683685795
Journal of Organic Chemistry,"Ester Dienolate [2,3]-Wittig Rearrangement in Natural Product Synthesis:  Diastereoselective Total Synthesis of the Triester of Viridiofungin A, A<sub>2</sub>, and A<sub>4</sub>","[structure: see text] An ester dienolate [2,3]-Wittig rearrangement was utilized to access the alkylated citric acid skeleton 6 that is characteristic for the viridiofungins and other members of the alkyl citrate family of secondary natural products. The [2,3]-sigmatropic rearrangement of (Z,Z)-15 provided the rearrangement product (+/-)-syn-16 in moderate yield and with very good diastereoselectivity. A Julia-Kocienski olefination efficiently served to connect the polar head (+/-)-syn-26 with the lipophilic tail (32a-c) of the viridiofungins. Amide formation between the racemic viridiofungin precursors 35a-c and the enantiomerically pure amino acid L-tyrosine methyl ester followed by preparative reversed-phase HPLC provided the isopropyl dimethyl ester of viridiofungin A ((+)-39a), A2 ((+)-39b), and A4 ((+)-39c) as well as the nonnatural diastereomers (-)-38a-c.",10.1021/jo0505270,2005-06-16,0.5823284733038845
Tetrahedron,Novel transformation of penicillin into penem nucleus : synthesis of 2-carboxylpenem derivative,,10.1016/s0040-4039(00)81695-0,1983-01-01,0.5823257586327318
Organic Letters,Asymmetric Total Synthesis of (+)-Phoslactomycin B,"(+)-Phoslactomycin B was synthesized by a highly enantio- and stereoselective approach involving asymmetric pentenylation, Suzuki-Miyaura coupling, ring-closing metathesis, asymmetric dihydroxylation, and Stille coupling. The synthetic method developed enables us to synthesize three other isomers concerning the C11-OH and Delta12-double bond.",10.1021/ol8004672,2008-05-08,0.5823232551289145
Tetrahedron,Asymmetric synthesis of an important precursor to 5′-nor carbocyclic nucleosides,"An asymmetric hetero-Diels-Alder reaction involving an amino acid-derived acylnitroso dienophile was utilized to synthesize (1S, 4R)-4-[N-(tert-butoxycarbonyl)amino]-2-cyclopentene-1-ol (4). The amino acid chiral auxiliary was removed by the Edman degradation. This enantiomerically pure aminoalcohol is a key intermediate in the synthesis of 5′-nor carbocyclic nucleosides.",10.1016/s0040-4039(97)00511-x,1997-04-01,0.5823228503772568
Tetrahedron,Synthesis of two key intermediates required for the construction of the bis-spiroacetal moiety of epi-17-deoxy-(0–8)-salinomycin,,10.1016/s0040-4039(00)84784-x,1986-01-01,0.5823223739120893
Tetrahedron,"A formal asymmetric synthesis of apratoxin D via advanced-stage asymmetric ACC α,α-bisalkylation of a chiral nonracemic ketone",,10.1016/j.tetlet.2015.04.022,2015-04-11,0.5823190929919853
Journal of Organic Chemistry,Halide-Terminated <i>N</i>-Acyliminium Ion−Alkyne Cyclizations:  A New Construction of Carbacephem Antibiotics,"A series of 4-(3-alkynyl)azetidinones 13 was prepared from 4-(phenylsulfonyl)azetidine-2-one ( 9 ) and isopropyl glyoxylate hydrate. The 3-pentynyl ( 13a ) and 4-phenyl-3-butynyl ( 13b ) azetidinone acetates underwent 6-exo cyclization when treated with 3 equiv of SnCl 4 at 0 °C to provide 3-(1-chloroalkylidene)carbacephems 15a (65%) and 15b (33%) respectively. In contrast, the 3-butynyl ( 13d ) and 4-(trimethylsilyl)-3-butynyl ( 13c ) azetidinone acetates underwent 7-endo cyclization under similar conditions to give 1-azabicyclo[5.2.0]nonenes 14a (11%) and 14b (71%), respectively. Beginning with penicillin degradation product 18, the more elaborate 3-pentynyl azetidinone cyclization substrate 27 was prepared in seven steps. Exposure to 27 to 3 equiv of SnCl 4 in CH 2 Cl 2 at 0 °C for 6 h, followed by allowing the reaction mixture to warm to rt, provided the desired 3-(1-chloroethylidene)carbacephem 28 in 60% yield and high (>99%) enantiometric purity. Cleavage of the chloroethylidene group of 28 with ozone gave 3-hydroxy carbacephem 29 in 77% yield. Since this intermediate has been converted in three steps to loracarbef ( 3 ), a new formal total synthesis of this carbacephem antiboitic was concluded.",10.1021/jo971433w,1997-12-01,0.5823167244273741
Organic Letters,Modular and Stereoselective One-Pot Total Synthesis of Icosasaccharide Motif from <i>Cordyceps sinensis</i> EPS-1A Glycan,"The first stereoselective one-pot synthesis of the icosasaccharide motif of EPS-1A glycan from Cordyceps sinensis has been achieved. The synthetic approach highlights the following features: (1) merging reagent modulation and remote anchimeric assistance α-glycosylation strategy for the highly stereoselective formation of five and ten continuous 1,2- cis glucosidic bonds; (2) the strategic employment of glycosyl N -phenyltrifluoroacetimidates and glycosyl o -(1-phenylvinyl)benzoates as the matched pair for efficient orthogonal one-pot synthesis; and (3) [11 + 8 + 1] orthogonal one-pot glycosylation for the efficient assembly of the target icosasaccharide.",10.1021/acs.orglett.3c02842,2023-10-03,0.5823153280680398
Synthesis,A Facile Synthesis of 3-Substituted Glutaraldehyde Monoacetals from Nitriles,"All articles of this category 3-Substituted glutaraldehyde monoacetals 7 have been prepared in 48-58% overall yield, consecutively by the alkylation of nitriles, first with 2-bromo-1,1-diethoxyethane (2) and then with 2-iodomethyl-1,3-dioxolane (4) , followed by removal of the cyano group and selective hydrolysis of the diethyl acetal function.",10.1055/s-1991-26497,1991-01-01,0.5823126456094387
European Journal of Organic Chemistry,Synthetic Strategy towards a Carbocyclic <i>N</i>‐Acetylneuraminic Acid,"Abstract In the study of glycosidases, a class of activity‐based probes (ABPs), that are carbocyclic mimics of natural carbohydrates and can covalently bind the enzyme, have proven to be useful tools. This type of ABP has however not yet been reported for sialidases, glycosidases involved in various important biological processes in both health and disease, which hydrolyse terminal sialic acids. Here we present our study towards the synthesis of a carbocyclic sialic acid suitable for conversion into ABPs. We developed a route starting from a chiral furanone that includes a key early stage nitrone [3+2] cycloaddition to install most of the chiral centres present in N ‐acetylneuraminic acid. The final stereocentre is installed via a Barbier alkylation, after which a ring closing metathesis forms the pivotal carbocyclic intermediate. Due to challenges in the final stretch, we were not able to convert this intermediate into an N ‐acetylneuraminic acid ABP. However, the work presented here still represents a versatile route to potential future carbocyclic sialic acid derivatives.",10.1002/ejoc.202200297,2022-06-27,0.5823126422269391
Angewandte Chemie International Edition,Synthesis of [8]Cycloparaphenylene from a Square‐Shaped Tetranuclear Platinum Complex,Square goes to loop: A selective synthesis of [8]cycloparaphenylene under mild and neutral reaction conditions was achieved in a small number of steps and in a high yield through the square-shaped platinum biphenyl intermediate 1. Compound 1 is the smallest cycloparaphenylene derivative synthesized to date.,10.1002/anie.200905659,2009-12-14,0.5823125591298787
Journal of the American Chemical Society,"Total Synthesis of (+)-Roxaticin via C−C Bond Forming Transfer Hydrogenation: A Departure from Stoichiometric Chiral Reagents, Auxiliaries, and Premetalated Nucleophiles in Polyketide Construction","A total synthesis of the oxo-polyene macrolide (+)-roxaticin is achieved in 20 steps from 1,3-propanediol. In this approach, 9 of 10 C-C bonds formed in the longest linear sequence are made via metal catalysis, including 7 C-C bonds formed by iridium catalyzed alcohol C-C coupling. Notably, the present synthesis, which represents the most concise preparation of any oxo-polyene macrolide reported to date, is achieved in the absence of chiral reagents and chiral auxiliaries with minimal use of premetalated C-nucleophiles.",10.1021/ja1082798,2010-10-20,0.5822957667018059
Organic Process Research & Development,"Benign and High-Yielding, Large-Scale Synthesis of Diphenylphosphinodithioic Acid and Related Compounds","Diphenylphosphinodithioic acid ( 6b ) and its triethyl ammonium salt ( 6a ) were prepared by two new synthetic pathways, each employing cheap and readily available starting materials. These facile one-pot reactions were conducted on a kilogram scale and produced the desired products in high yield and quality, thereby surpassing all previously known routes. The synthesis of triethyl ammonium salts of 6 H -dibenzo[ c, e ][1,2]oxaphosphinine-6-thiolate 6-sulfide ( 3a ) was also further improved.",10.1021/op300147f,2012-11-22,0.5822894278966548
Synthesis,Enantioselective Synthesis of Hexahydroisobenzofuran and Hexahydroisoindole Derivatives with Quaternary Stereocenters,"Oxo esters with pyrrolidine and tetrahydrofuran rings were converted into optically active isobenzofuran and isoindole derivatives. The key step of the sequence was a copper-catalyzed asymmetric Michael reaction with methyl vinyl ketone and en­amines prepared from the oxo esters and l-valine diethylamide. The chiral auxiliary was cleaved from the products during workup and 1,5-diketones with a quaternary stereocenter are obtained with 97-99% ee. Subsequent annulation reactions were achieved in two steps via the intermediate aldol products.",10.1055/s-0030-1258419,2011-03-01,0.5822893796866001
Angewandte Chemie International Edition,Enantioselective Total Synthesis of Avarol and Avarone,"Formation of the C11-C1' bond through application of Barton's radical decarboxylation and quinone addition is the cornerstone of a new convergent and concise synthesis of the marine metabolites avarol (1) and avarone (2; see scheme), for which antimitotic, antileukemic, and antiviral effects have been reported.",10.1002/(sici)1521-3773(19991018)38:20<3089::aid-anie3089>3.0.co;2-w,1999-10-18,0.582287752874284
Angewandte Chemie International Edition,Biomimetic Total Synthesis of Enterocin,The first chemical total synthesis of the highly oxygenated polyketide enterocin has been accomplished. The key step of the synthesis was a late-stage biomimetic reaction cascade involving two intramolecular aldol reactions in which each step proceeded in 52 % yield (averaged) and which established four of the seven stereogenic centers. The pivotal precursor for the cascade reaction was assembled from three readily available building blocks. A chiral dithioacetal with two stereogenic centers originating from L-arabinose represented the core fragment to both ends of which the other building blocks were attached by aldol reactions. The remaining stereogenic center was installed by Davis oxygenation immediately prior to the key step.,10.1002/anie.202108157,2021-07-19,0.5822864017129731
Organic Letters,A Convergent Strategy for the Synthesis of β-Carba-galacto-disaccharides,"[reaction in text] A convergent strategy for the synthesis of beta-carba-galacto-disaccharides is illustrated by the preparation of 1 and 4, from a central ""glycone"" component 22, and the corresponding ""aglycone"" segments, monosaccharide alcohols, 23a or 23b. The key step is the formation of the carbasugar ring via an oxocarbenium ion-enol ether cyclization.",10.1021/ol0156906,2001-04-05,0.5822806526335791
Angewandte Chemie International Edition,Total Synthesis of Dragocins A−C through Electrochemical Cyclization,"The first total synthesis of dragocins A-C, remarkable natural products containing an unusual C4' oxidized ribose architecture bridged by a polyhydroxylated pyrrolidine, is presented through a route featuring a number of uncommon maneuvers. Several generations towards the target molecules are presented, including the spectacular failure of a key C-H oxidation on a late-stage intermediate. The final route features rapid, stereocontrolled access to a densely functionalized pyrrolidine and an unprecedented diastereoselective oxidative electrochemical cyclization to forge the hallmark 9-membered ring. Preliminary studies suggest this electrochemical oxidation protocol is generally useful.",10.1002/anie.202401107,2024-02-15,0.5822804077998821
Organic Letters,Total Synthesis of (−)-Ecklonialactone B,"The total synthesis of (-)-ecklonialactone B as well as the 9,10-dihydro derivative by two different strategies is reported. The catalytic asymmetric Claisen rearrangement of Gosteli-type allyl vinyl ethers delivered elaborated α-keto ester building blocks. Ring-closing metatheses, including a notable diastereotopos-differentiating variant, a B-alkyl Suzuki-Miyaura cross-coupling reaction and a regio- and diastereoselective last-step epoxidation are key contributors.",10.1021/ol4028418,2013-11-12,0.5822756303274007
Tetrahedron,"An improved, scalable synthesis of bis-amino acids",,10.1016/j.tetlet.2016.09.032,2016-09-14,0.5822675034815671
Tetrahedron,A new convenient synthesis of aroyl cyanides via the formation of cyanohydrin nitrate intermediates,,10.1016/j.tetlet.2008.06.034,2008-06-13,0.582265480501081
Synlett,Formal Synthesis of 3-Deoxy-d-manno-Octulosonic Acid (KDO) and 3-Deoxy-d-arabino-2-heptulosonic Acid (DAH),Practical synthetic routes to 3-deoxy- d - manno -octulo­sonic acid (KDO) and 3-deoxy- d - arabino -2-heptulosonic acid (DAH) from common sugar substrates are reported. Chain homologation of the sugar substrates was accomplished by Wittig olefination and Corey–Fuchs alkynylation. A new cyclization strategy was investigated to access the desired pyranosyl isomer of the KDO target.,10.1055/s-0032-1317932,2012-12-21,0.582260004915587
Journal of Organic Chemistry,"Nucleophilic Addition of Benzimidazoles to Alkynyl Bromides/Palladium-Catalyzed Intramolecular C–H Vinylation: Synthesis of Benzo[4,5]imidazo[2,1-<i>a</i>]isoquinolines","An efficient ""one-pot"" route for the synthesis of benzo[4,5]imidazo[2,1-a] isoquinolines has been developed via nucleophilic addition of 2-aryl benzimidazoles to alkynyl bromides and subsequent palladium-catalyzed intramolecular C-H vinylation.",10.1021/jo302471z,2012-12-28,0.582259759659178
Tetrahedron,Total synthesis of collagen crosslinker deoxypyridinoline,"Collagen, a fibrous protein, accounts for 30 % of all proteins in the human body and serves as an essential extracellular matrix component that imparts mechanical strength to connective tissues such as skin and bones. Deoxypyridinoline , a collagen crosslinking amino acid , was first isolated from bovine bone in 1982. This compound is released into the bloodstream during bone resorption without being reused and has recently garnered attention as a biomarker for osteoporosis. In this study, we achieved the total synthesis of deoxypyridinoline, with a 22 % overall yield, in five steps from commercially available protected amino acids. The synthesis would aid a quantitative analysis of deoxypyridinoline as an alternative to isolating it from natural sources.",10.1016/j.tetlet.2025.155508,2025-02-14,0.5822585969443383
Synlett,"Recent Advances in the Synthesis of Functionalized Pyrazolo[1,5-a]pyrimidines via C–H Functionalization","Abstract Recent developments in the synthesis of functionalized pyrazolo[1,5-a]pyrimidines through C–H functionalization have been summarized in this account, covering the synthesis of 3-halo, 3-nitro, 3-formyl, 3-acetyl, 3-sulfenyl, 3-selenyl, and 3-thiocyanato pyrazolo[1,5-a]pyrimidines and bis(pyrazolo[1,5-a]pyrimidin-3-yl)methanes. The main focus highlights the utilization of sustainable conditions in designing the protocols. Mechanistic aspects of these protocols have also been discussed in detail. 1 Introduction 2 Discussion 2.1 Synthesis of 3-Halo Pyrazolo[1,5-a]pyrimidines 2.2 Synthesis of 3-Nitro Pyrazolo[1,5-a]pyrimidines 2.3 Synthesis of 3-Formyl Pyrazolo[1,5-a]pyrimidine 2.4 Synthesis of 3-Acetyl Pyrazolo[1,5-a]pyrimidines 2.5 Synthesis of 3-Sulfenyl Pyrazolo[1,5-a]pyrimidines 2.6 Synthesis of 3-Selenyl Pyrazolo[1,5-a]pyrimidines 2.7 Synthesis of 3-Thiocyanated Pyrazolo[1,5-a]pyrimidines 2.8 Synthesis of Bis(pyrazolo[1,5-a]pyrimidinyl)methanes 3 Conclusions and Outcome",10.1055/a-2526-0771,2025-01-27,0.582251816168528
Tetrahedron,Synthesis of new polyhalogenoalkyl-containing phosphonates with an enaminone core and their use in the preparation of fluorinated heterocycles,,10.1016/j.tetlet.2010.06.123,2010-07-02,0.5822462738105402
Tetrahedron,A route to functionalized mitosones,,10.1016/s0040-4039(01)83148-8,1977-01-01,0.5822411588313012
Tetrahedron,A new synthesis of potent antitumor saponin OSW-1 via Wittig rearrangement,,10.1016/j.tetlet.2007.11.087,2007-11-26,0.5822392143214062
Tetrahedron,"An alternative route to cis-1,2-fused oxazolidine-2-thione from 1,2-O-sulfinyl sugar derivatives",,10.1016/0040-4039(95)01054-l,1995-07-01,0.5822364207195491
Tetrahedron,"An Alternative Route to cis-1,2-Fused Oxazolidine-2-Thione from 1,2-O-Sulfinyl Sugar Derivatives",,10.1016/00404-0399(50)1054l-,1995-07-24,0.5822364207195491
Synlett,Addition of Allylmagnesium Bromide to ROPHy/SOPHy Aldoximes: Asymmetric Synthesis of Protected β-Amino Acids,All articles of this category A new asymmetric synthesis of protected β-amino acids is described in which the key step is the diastereoselective addition of allylmagnesium bromide to O- (1-phenylbutyl) aldoximes. oxime ether - hydroxylamine - homoallylamine - β-amino acid,10.1055/s-1998-1767,1998-07-01,0.5822352648422832
Synthesis,Synthesis of 5-(Hydroxymethyl)pyrrolidin-2-ones by Cyclization of Amide Dianions with Epibromohydrin,The reaction of amide and thioamide dianions with epibromohydrin resulted in regioselective formation of 5-(hydroxy­methyl)pyrrolidin-2-ones (pyroglutaminols) and -thiones. The cyclization of the dianion of N-(2-tert-butylphenyl)acetamide with epibromohydrin afforded racemic axially chiral 1-(2-tert-butyl­phen­yl)-5-(hydroxymethyl)pyrrolidin-2-one with high diastereo­selectivity.,10.1055/s-2006-942354,2006-05-23,0.5822350709989722
Organic Letters,Mild Construction of 3-Methyl Tetramic Acids Enabling a Formal Synthesis of Palau’imide,"A general method to construct 3-methyl-4-O-methylated tetramic acids displaying a C-5 stereocenter is presented. The synthetic sequence employs a SmI(2)-mediated cyclization, whereby the chirality of the emerging tetramic acid core is retained from the starting chiral amino acid. Application to palau'imide is discussed.",10.1021/ol301556a,2012-07-17,0.5822349662423657
Synthesis,"Diversified Synthesis of 2-(4-Oxo[1,2,3]triazolo[1,5-a]quinoxalin-5(4H)-yl)acetamide Derivatives through Ugi-4-CR and Copper-Catalyzed Tandem Reactions","A diversified synthesis of 2-(4-oxo[1,2,3]triazolo-[1,5-a]quin­oxalin-5(4H)-yl)acetamide derivatives is demonstrated. The protocol employs a Ugi four-component reaction for the assembling of N-(2-haloaryl)propynamide intermediates and followed by a copper-catalyzed tandem reaction of the synthetic N-(2-haloaryl)propynamides with sodium azide. Such a method provides rapid access to structurally varied and complex fused tricyclic scaffolds through readily available starting materials.",10.1055/s-0036-1590791,2017-07-11,0.5822304348361843
European Journal of Organic Chemistry,Mimicking the Main Events of the Biosynthesis of Drimentines: Synthesis of Δ8′‐Isodrimentine A and Related Compounds,"Drimentines are a family of tetracyclic alkaloids biosynthetically originating from the condensation of sesquiterpene units onto cyclic dipeptides. A straightforward assembly of the fused “pyrroloindoline–diketopiperazine” core of drimentines is described herein and used for the synthesis of Δ 8′ ‐isodrimentine A. The strategy involves a bio‐inspired indole dearomatization of a tryptophan‐containing cyclodipeptide by a drimane‐type decaline followed by the intramolecular trapping of the resulting indolenine intermediate in an uninterrupted reactive sequence. The starting diketopiperazine was prepared by classical peptidic coupling and the drimane‐type decaline from (+)‐sclareolide. A fully biomimetic approach with a linear sesquiterpene unit is also reported and led to farnesylated pyrroloindoline–diketopiperazines, which correspond to the proposed biosynthetic precursors of both drimentines A and D. The end product Δ 8′ ‐isodrimentine A and its congeners were evaluated in vitro for their cytotoxic activities against three human tumor cell lines.",10.1002/ejoc.201600444,2016-06-01,0.5822282233353302
Organic Letters,A Concise and Versatile Synthesis of Viridicatin Alkaloids from Cyanoacetanilides,The efficient synthesis of 3-hydroxy-4-arylquinolin-2(1H)-ones through one-pot Knoevenagel condensation/epoxidation of cyanoacetanilides followed by decyanative epoxide-arene cyclization is described. A convergent assembly with functionalized aldehydes allows for rapid synthesis with diverse substitution patterns. Isolation of 3-hydroxy-4-arylquinolin-2(1H)-ones is readily accomplished by precipitation and filtration.,10.1021/ol900255g,2009-03-03,0.5822264997012467
Tetrahedron,A stereoselective synthesis of (±)-veadeiroic acid and (±)-veadeirol - two novel diterpenes with cleistanthane skeleton,,10.1016/s0040-4039(00)79725-5,1991-07-01,0.5822251938329787
Tetrahedron,"The rapid reaction of benzhydryl sulfones with CCl4-KOH. A new route to 1,1-diarylalkenes",,10.1016/s0040-4039(01)82418-7,1974-01-01,0.5822119594725408
Journal of Organic Chemistry,"Total Syntheses of (±)-Isosteviol and (±)-Beyer-15-ene-3β,19-diol by Manganese(III)-Based Oxidative Quadruple Free-Radical Cyclization","Tetraene 1 was prepared in nine steps from the known propargylic alcohol 7 in 17% overall yield or as a 2:1 E/Z mixture in only five steps in 7% overall yield. Oxidative cyclization of 1 with 2 equiv of Mn(OAc) 3 ·2H 2 O and 1 equiv of Cu(OAc) 2 in MeOH at 25 °C provided 35% of tetracycle 2 . Further elaboration provided (±)-isosteviol ( 3 ) in six steps in 51% yield and (±)-beyer-15-ene-3β,19-diol in four steps in 17% yield.",10.1021/jo981238x,1998-10-01,0.5822114029416826
Journal of Organic Chemistry,Total Synthesis of Heliophenanthrone,"The total synthesis of rac-heliophenanthrone (3a) was achieved by a convergent approach, making use of a transition-metal-catalyzed domino process with an intramolecular Diels-Alder reaction at an isobenzopyrylium cation as key step.",10.1021/jo050400a,2005-06-24,0.5821994588879269
Tetrahedron,"First total synthesis of (+)-vedelianin, a potent antiproliferative agent",,10.1016/j.tetlet.2011.01.137,2011-02-04,0.5821979920606024
Tetrahedron,First total synthesis of potent antitumour agent (+)-goniopypyrone,,10.1016/s0040-4039(00)61654-4,1993-01-01,0.5821979920606024
Journal of Organic Chemistry,Synthesis of Luffarin L and 16-<i>epi</i>-Luffarin L Using a Temporary Silicon-Tethered Ring-Closing Metathesis Reaction,The first synthesis of luffarin L (1) and 16-epi-luffarin L (2) by a silicon-tethered ring closing metathesis as a key step has been achieved. The stereochemistry and absolute configuration of the natural sesterterpenolide luffarin L (1) and a new route for the stereoselective synthesis of sesterterpenolides with a luffarane skeleton have been established.,10.1021/acs.joc.5b00876,2015-05-15,0.5821959829482327
Angewandte Chemie International Edition,"Catalytic Asymmetric Alkynylation of 3,4‐Dihydro‐β‐carbolinium Ions Enables Collective Total Syntheses of Indole Alkaloids","Chiral tetrahydro-β-carboline (THβC) is not only a prevailing structural feature of many natural alkaloids but also a versatile synthetic precursor for a vast array of monoterpenoid indole alkaloids. Asymmetric synthesis of C1-alkynyl THβCs remains rarely explored and challenging. Herein, we describe the development of two complementary approaches for the catalytic asymmetric alkynylation of 3,4-dihydro-β-carbolinium ions with up to 96 % yield and 99 % ee. The utility of chiral C1-alkynyl THβCs was demonstrated by the collective total syntheses of seven indole alkaloids: harmicine, eburnamonine, desethyleburnamonine, larutensine, geissoschizol, geissochizine, and akuammicine.",10.1002/anie.202112383,2021-09-28,0.5821932234877464
Synthesis,"A New Strategy for the Synthesis of Furan-3,4-dicarboxylic Acid","A facile route to furan-3,4-dicarboxylic acid is described. Dimethylmaleic anhydride (1) on NBS-bromination followed by aqueous KOH treatment gave bis(hydroxymethyl)maleic anhydride (3), which on intramolecular Mitsunobu ring closure followed by esterification and DDQ-oxidation furnished the desired esters of furan-3,4-dicarboxylic acid 7a/b.",10.1055/s-2002-31967,2002-01-01,0.5821926842805225
Journal of Organic Chemistry,Asymmetric Total Synthesis of Caribenol A via an Intramolecular Diels–Alder Reaction,"A total synthesis of the caribenol A (1), a novel natural product with an intriguing tetracyclic framework, has been achieved. The synthesis features an intramolecular Diels-Alder (IMDA) reaction for the facile construction of the tricyclic [5-7-6] skeleton of caribenol A (1) and a biomimetic oxidation reaction for the formation of the 2-hydroxyfuran-2(5H)-one motif of caribenol A (1) as key steps. This synthetic approach also reveals that the sp(2) carbon at C(2) in substrate 8 is a critical factor for the formation of the tricyclic [5-7-6] skeleton in 7.",10.1021/jo4006156,2013-05-14,0.5821909924731751
Tetrahedron,"De novo asymmetric synthesis of two 5-amino-5,6-dideoxy-D-allose derivatives",,10.1016/s0040-4039(00)77271-6,1994-08-01,0.5821886602948686
Tetrahedron,"An asymmetric synthesis of (1S,4R)-4-amino-2-cyclopentenol derivatives",,10.1016/s0040-4039(99)00002-7,1999-02-01,0.5821886602948686
Tetrahedron,Novel synthesis of biphenylene and its derivatives using intramolecular coupling of zincacyclopentadienes,,10.1016/s0040-4039(98)01082-x,1998-07-01,0.5821876548837899
Tetrahedron,Enantioselective synthesis of α-hydroxy thioesters via oxazaborolidine-mediated reduction of α-phenylthio enones,,10.1016/s0040-4039(98)00170-1,1998-04-01,0.5821829093986175
Organic Letters,"Design, Synthesis, and Biological Evaluation of a Potent, PKC Selective, B-Ring Analog of Bryostatin","[structure: see text] The first member of a new class of five-membered B-ring analogs of bryostatin has been synthesized and tested for its ability to bind and translocate protein kinase C (PKC). This synthesis extends the utility of our previously introduced macrotransacetalization strategy to the formation of five-membered dioxolane B-ring analogs. This analog exhibits potent, single-digit nanomolar affinity to PKC and selectively translocates novel PKC isozymes.",10.1021/ol060457z,2006-03-31,0.5821786729343765
Journal of Organic Chemistry,"Palladium-Catalyzed Double Reductive Cyclization of 2,3-Dinitro-1,4-dialkenylbenzenes. Synthesis of 1<i>H</i>,8<i>H</i>-Pyrrolo[3,2-<i>g</i>]indoles","]indole has been developed. The key and ultimate step is a double palladium-catalyzed, carbon monoxide mediated reductive cyclization of 1,4-dialkenyl-2,3-dinitrobenzenes. The cyclization precursors were prepared by a double Kosugi-Migita-Stille cross coupling of 1,4-dibromo-2,3-dinitrobenzene with an alkenyltin reagent to give symmetrical products. Unsymetrical cyclization precursors were prepared by two sequential cross couplings using 4-iodo-2,3-dinitrophenyl trifluoromethanesulfonate as the starting material.",10.1021/acs.joc.9b03290,2020-03-04,0.5821741698648002
Journal of Organic Chemistry,Post-Ugi Transformations for the Access to Pyrrolobenzodiazepine Scaffolds with Different Degrees of Unsaturation,"][1,4]benzodiazepine-5-ones is described. The compounds were prepared according to a three-step sequence, involving an Ugi reaction, building of the pyrrolo nucleus, and reduction-cyclization to the corresponding diazepine. Depending on the amine employed in the synthesis of the Ugi adducts, different unsaturation degrees could be obtained in the pyrrolo ring (saturated or with endo or exo unsaturations), a key feature determining their biological activity, as it affects the affinity of the pyrrolobenzodiazepines toward DNA and thus their cytotoxicity. This synthetic methodology represents a significant improvement with respect to those described in the literature so far, as it uses inexpensive and commercially available starting materials without needing derivatization or the use of protecting groups.",10.1021/acs.joc.9b02995,2020-01-13,0.5821710639244195
Tetrahedron,"Synthesis of demethylallosamidin, a yeast chitinase inhibitor; use of disaccharide glycosyl donor carrying novel neighboring group",,10.1016/s0040-4039(00)73136-4,1994-06-01,0.5821675790481355
Angewandte Chemie International Edition,"A Copper‐Catalyzed Tandem Synthesis of Indolo‐ and Pyrrolo[2,1‐<i>a</i>]isoquinolines",Isoquinoline ring the changes: A novel strategy for the title reaction involves ortho-haloarylalkynes which undergo sequential intermolecular addition of N heterocycles onto alkynes and subsequent intramolecular ring closure by arylation. The process involves the use of hydroxymethyl benzotriazole as an efficient and inexpensive ligand for the CN and CC coupling reactions.,10.1002/anie.200804427,2008-12-31,0.5821632266921903
Journal of Organic Chemistry,Palladium-Catalyzed Acylations: One-Pot Synthesis of Indenones,"An efficient, one-pot synthesis of substituted indenones was accomplished starting from simple o-iodoketones and aldehydes. [Pd]-catalyzed direct acylation of o-iodoketones with aldehydes was employed as the key step. Subsequent intramolecular aldol condensation afforded the indenones. Notably, a variety of indenones were achieved. Significantly, the natural product neolignan was accomplished in one pot.",10.1021/acs.joc.6b02453,2016-12-10,0.5821627639916056
Synthesis,"A New General Synthesis of 2,5-Disubstituted Thiophenes Starting From β-Nitro-β,γ-Unsaturated Ketones and 4-Methoxybenzyl Mercaptan","Herein, we report a practical synthesis of 2,5-disubstituted thiophenes. The protocol features an initial base-promoted Michael addition of 4-methoxybenzyl mercaptan to β-nitro-β,γ-unsaturated ketones, followed by an acid-mediated cyclization of the resulting adducts. This one-pot procedure affords the desired thiophene derivatives in good overall yields.",10.1055/a-2714-8785,2025-10-01,0.5821615901062828
Tetrahedron,A copper-catalyzed domino radical cyclization route to benzospiro-indolizidinepyrrolidinones,,10.1016/j.tetlet.2007.07.211,2007-08-04,0.5821597615722349
Chemical Science,Organocatalytic enantioselective synthesis of C <sub> sp <sub>2</sub> </sub> –N atropisomers <i>via</i> formal C <sub> sp <sub>2</sub> </sub> –O bond amination,An organocatalyzed asymmetric synthesis of C sp2 –N atropisomers by formal C sp2 –O amination has been established from 3-alkynyl-3-hydroxyisoindolinones and 1-methylnaphthalen-2-ols.,10.1039/d3sc06707f,2024-01-01,0.5821524782017357
Tetrahedron,"Synthesis and NMDA receptor binding of 2-amino-7,7-difluoro-7-phosphonoheptanoic acid",,10.1016/s0040-4039(01)93411-2,1989-01-01,0.5821501704458286
Organic Letters,Total Synthesis of Mycocyclosin,"The first total synthesis of mycocyclosin, a diketopiperazine natural product isolated from M. tuberculosis, is described. While direct oxidative coupling of tyrosine phenolic groups was unsuccessful, construction of the highly strained bicyclic framework was successfully accomplished through an intramolecular Miyaura-Suzuki cross-coupling to generate the biaryl linkage.",10.1021/ol300831t,2012-04-20,0.5821457359367441
Tetrahedron,High yield protection of purine ribonucleosides for phosphoramidite RNA synthesis,,10.1016/s0040-4039(99)00733-9,1999-05-01,0.582145069634588
Tetrahedron,High yield protection of purine ribonucleosides for H-phosphonate RNA synthesis,,10.1016/s0040-4039(97)01767-x,1997-10-01,0.582145069634588
Organic Letters,"Studies Directed toward the Total Synthesis of Azaspiracid:  Stereoselective Construction of C<sub>1</sub>−C<sub>12</sub>, C<sub>13</sub>−C<sub>19</sub>, and C<sub>21</sub>−C<sub>25</sub> Fragments","[reaction: see text] The efficient entry to the C(1)-C(12), C(13)-C(19), and C(21)-C(25) fragments of azaspiracid is outlined. The C(1)-C(12) portion is constructed using a key asymmetric allenyl borane addition to the corresponding alpha,beta-unsaturated aldehyde. The synthesis of the C(13)-C(19) portion utilizes an Evans asymmetric alkylation followed by Sharpless asymmetric dihydroxylation. In addition, a novel solution to the mismatched effects of a neighboring chiral oxazolidinone during a Sharpless dihydroxylation is detailed.",10.1021/ol006674w,2000-11-01,0.5821408162434402
Synlett,Anodic Cyanation of (<i>S</i>)-(-)-1-(1-Phenylethyl)piperidine: an Expeditious Synthesis of (<i>S</i>)-(+)-Coniine,"A short and efficient asymmetric synthesis of enantiopure (S)-(+)-coniine is reported. Anodic cyanation of (-)-1-[(1S)-1-phenylethyl]piperidine, derived from [(1S)-1-phenylethyl]amine, results in regioselective formation of the corresponding α-amino­nitrile, which was alkylated with propyl iodide to give a bifunc­tional derivative. The latter underwent a stereoselective reductive decyanation (80% de), the product of which was hydrogenolyzed to afforded (S)-(+)-coniine (99% ee) with an overall 35% yield from (-)-1-[(1S)-1-phenylethyl]piperidine.",10.1055/s-2006-944214,2006-07-01,0.5821364224692231
Organic Letters,Total Synthesis of <i>seco</i>-Plakortolide E and (−)-<i>ent</i>-Plakortolide I: Absolute Configurational Revision of Natural Plakortolide I,"A first total synthesis of (-)-ent-plakortolide I and seco-plakortolide E was accomplished from (S)-2-methylglycidol. The relevant key reactions involve a diastereoselective Mukaiyama aldol reaction, a regioselective hydroperoxysilylation, and elaboration of the 1,2-dioxane ring by intramolecular Michael addition of a hydroperoxide group to a butenolide. This synthesis allowed the revision of the absolute configuration of plakortolide I and structural revision of plakortolide E.",10.1021/ol203185f,2011-12-22,0.5821345280493921
Tetrahedron,Bismuth trichloride catalyzed synthesis of α-aminonitriles,,10.1016/j.tetlet.2004.08.071,2004-09-01,0.5821343419724004
Tetrahedron,In(OTf)3-catalyzed synthesis of 7-acylindoles and 2-aminoquinolines from ynamides and anthranils,,10.1016/j.tetlet.2024.155054,2024-04-12,0.5821343419724004
Tetrahedron,Ytterbium triflate catalyzed synthesis of chlorinated lactones,,10.1016/j.tetlet.2010.09.015,2010-09-19,0.5821343419724004
Tetrahedron,"Sc(OTf)3-catalyzed synthesis of pyrano[3,2-b]-1-benzopyrans from d-glycals",,10.1016/s0040-4039(02)00816-x,2002-06-01,0.5821343419724004
Tetrahedron,Ytterbium-catalyzed synthesis of dihydropyridines,,10.1016/j.tetlet.2011.06.070,2011-06-27,0.5821343419724004
Tetrahedron,Nano ceria catalyzed synthesis of α-aminophosphonates under ultrasonication,,10.1016/j.tetlet.2011.04.112,2011-05-07,0.5821343419724004
Tetrahedron,Regiospecific allylation of acetals with allylsilanes catalyzed by iodotrimethylsilane. Synthesis of homoallylethers,,10.1016/0040-4039(81)80140-2,1981-01-01,0.5821343419724004
Tetrahedron,Cobalt-catalyzed synthesis of pyridines from acetylenes and nitriles,,10.1016/s0040-4039(01)86920-3,1973-01-01,0.5821343419724004
Synthesis,Synthesis of Isocoumarin via PTSA-Catalyzed Annulation of Diarylalkynes,International audience,10.1055/s-2008-1072575,2008-05-01,0.5821343419724004
Synthesis,Cobaltocene Catalyzed Synthesis of Pyridines,,10.1055/s-1976-23943,1976-01-01,0.5821343419724004
Tetrahedron,Ytterbium triflate catalyzed synthesis of β-enaminones,,10.1016/j.tetlet.2007.02.064,2007-02-17,0.5821343419724004
Tetrahedron,"Indium trichloride catalyzed glycosidation. An expeditious synthesis of 2,3-unsaturated glycopyranosides",,10.1016/s0040-4039(99)02266-2,2000-02-01,0.5821343419724004
Tetrahedron,Bismuth-catalyzed synthesis of anthracenes via cycloisomerization of o-alkynyldiarylmethane,,10.1016/j.tetlet.2015.10.111,2015-10-31,0.5821343419724004
Tetrahedron,CuBr2 catalyzed synthesis of 3-furylphthalides,,10.1016/j.tetlet.2016.02.070,2016-02-18,0.5821343419724004
Tetrahedron,α-Chymotrypsin-catalyzed (3 + 7) segment synthesis of the luteinizing hormone releasing hormone,,10.1016/s0040-4039(00)78861-7,1992-05-01,0.5821343419724004
Tetrahedron,"Gold-catalyzed glycosidations: synthesis of 1,6-anhydro saccharides",,10.1016/j.tetlet.2010.09.004,2010-09-13,0.5821343419724004
Synthesis,Novel and Efficient Synthesis of Spirocyclic Morpholinones as Precursors of ψ[CH2O] Dipeptide Isosteres,,10.1055/s-1999-6050,1999-01-01,0.5821289095252581
Tetrahedron,A facile route to polysubstituted 2-hydroxy-3-nitro-cyclopentanones via a linear α-ketoenamine,,10.1016/s0040-4039(00)80446-3,1988-01-01,0.5821244086712223
Angewandte Chemie International Edition,Total Synthesis of (−)‐Arborisidine,"An asymmetric total synthesis of cage-like indole alkaloid arborisidine is presented. The new synthetic strategy features a catalytic parallel kinetic resolution based on ambident nucleophilicity (C3/N) of indole to set the absolute configurations of the two quaternary chiral centers, and a 5-exo-trig radical cyclization to form the bridged nitrogen-containing five-membered ring.",10.1002/anie.202101161,2021-03-29,0.5821241170015877
Organic Letters,Synthesis of 2-Oxazolidinones from β-Lactams:  Stereospecific Total Synthesis of (−)-Cytoxazone and All of Its Stereoisomers,"The synthetic correlation between two different antibiotic frameworks, the beta-lactams and 2-oxazolidinones, is described for the first time. In this approach, 2-oxazolidinones are prepared in stereomerically pure form from 3-hydroxy beta-lactams by a ring-opening-cyclization isomerization process. Application of this methodology to the total synthesis of the cytokine modulator, (-)-cytoxazone, and its three stereoisomers is demonstrated. [reaction: see text].",10.1021/ol062752p,2007-01-20,0.5821209379383642
Journal of Organic Chemistry,Rapid Assembly of Oligosaccharides: A Highly Convergent Strategy for the Assembly of a Glycosylated Amino Acid Derived from PSGL-1,"P-Selectin and P-selectin glycoprotein ligand 1 (PSGL-1) are vascular adhesion molecules that play an important role in the recruitment of leukocytes to inflamed tissue by establishing leukocyte-endothelial and leukocyte-platelet interaction. P-Selectin binds to the amino-terminus of PSGL-1 through recognition of a sialyl Lewis(x) (SLe(x)) moiety linked to a properly positioned core-2 O-glycan and three tyrosine sulfate residues. We have developed a highly convergent synthesis of the PSGL-1 oligosaccharide linked to threonine based on the use of trichoroacetimidate donors and thioglycosyl acceptors that give products that can immediately be employed in a subsequent glycosylation step without the need for protecting group manipulations. Furthermore, by employing one-pot multistep glycosylation sequences the number of purification steps could be minimized. The process of oligosaccharide assembly was further streamlined by combining protecting group manipulations and glycosylations as a one-pot multistep synthetic procedure. The resulting PSGL-1 oligosaccharide is properly protected for glycopeptide assembly. It is to be expected that the strategic principles employed for the synthesis of the target compound can be applied for the preparation of other complex oligosaccharides of biological and medical importance.",10.1021/jo901135k,2009-07-16,0.5821120975157764
Tetrahedron,"Chiral vicinal diols as platforms for separable diastereomers in Johnson–Claisen rearrangement: a new short route to (−)-nor-canadensolide, (−)-canadensolide and (−)-sporothriolide",,10.1016/j.tetlet.2008.12.084,2008-12-26,0.5820985253895247
Journal of Organic Chemistry,"I<sub>2</sub>/KI-Mediated Oxidative N–N Bond Formation for the Synthesis of 1,5-Fused 1,2,4-Triazoles from <i>N</i>-Aryl Amidines","An I2/KI-mediated oxidative N-N bond formation reaction is described. This new and environmentally benign approach allows for the convenient synthesis of a variety of 1,2,4-triazolo[1,5-a]pyridines and other 1,5-fused 1,2,4-triazoles from readily available N-aryl amidines in an efficient and scalable fashion.",10.1021/acs.joc.5b01183,2015-06-26,0.5820979875075702
Journal of Organic Chemistry,A Local Desymmetrization Approach to Piperidinyl Acetic Acid γ-Secretase Modulators,A desymmetrization-based approach for the synthesis of piperidinyl acetic acid γ-secretase modulators has been developed. The synthetic sequence features the use of N-tert -butanesulfinyl imine reduction and a diastereoselective lactam formation to set up the chiral centers. The synthetic utility is demonstrated by the concise asymmetric synthesis of γ-secretase modulator GSM-1.,10.1021/acs.joc.1c01970,2021-10-12,0.5820975382150672
Organic Process Research & Development,"Scale-Up Syntheses of Two Naturally Occurring Procyanidins:  (−)-Epicatechin-(4β,8)-(+)-catechin and (−)-Epicatechin-3-<i>O-</i>galloyl-(4β,8)-(−)-epicatechin-3-<i>O</i>-gallate","A scaleable process for the synthesis of two naturally occurring procyanidins, namely (−)-epicatechin-(4β,8)-(+)-catechin ( 1 ) and (−)-epicatechin-3- O -galloyl-(4β,8)-(−)-epicatechin-3- O -gallate ( 2 ), is described. The key steps were highlighted by improvements for the benzylation of (+)-catechin ( 3 ), stereoselective reduction of the C-3 keto group of (2 R )-5,7,3‘,4‘-tetrakis(benzyloxy)flavan-3-one ( 10 ), and coupling between 4-hydroxyethoxy-5,7,3‘,4‘-tetra- O -benzyl-(−)-epicatechin ( 11 ) and 5,7,3‘,4‘-tetra- O -benzyl-(+)-catechin ( 4 ) or 5,7,3‘,4‘-tetra- O -benzyl-(-)-epicatechin ( 6 ), respectively. The debenzylation performed in a biphasic system resulted in an improved yield and purity of the target compounds. The chemistry was scaled-up to produce multigram quantities of the title compounds ( 1 and 2 ) for various in vitro, ex vivo, and in vivo studies. Moreover, the scale-up process provided a detailed description for the preparation of multihundred to kilogram scale quantities of intermediates used in the synthesis of these two titled procyanidins.",10.1021/op700031n,2007-04-26,0.5820964067485996
Synlett,"Intramolecular Heck Reaction of Hex-2-enopyranosides: an Easy Entry to Cis-Fused Furo- or Pyrano[2,3b]pyranones","All articles of this category An efficient three-step sequence from glycals involving an intramolecular Heck reaction as a key step is described to produce chiral cis -fused furo- or pyrano[2,3b]pyrans. Alkyl hex-2-enopyranosides - palladium catalyst - cyclization - ”on-template” ring construction - pyranoids - furanoids",10.1055/s-1996-5402,1996-04-01,0.5820940765159038
Journal of Organic Chemistry,"Synthesis of 1,5- and 1,8-dihydroxyanthraquinones from a common intermediate. A direct synthesis of racemic 7-deoxyaklavinone","When quinone 6 was treated with diene I followed by oxidation, a 1,5-dihydroxyanthraquinone was obtained. When quinone 6 was subjected to a palladium-mediated aromatization, the reaulting bhydroxy-l,4naphthoquinone read with diene 7 followed by oxidation to produce a l,&amp;dihydroxyanthraquinone, a key intermediate in a direct synthesis of 7-deoxyaklavinone, a known synthetic precursor of aklavinone.",10.1021/jo00017a020,1991-08-01,0.5820909396753432
Synlett,First Stereocontrolled Reduction of Isoxazoline by Hydrogenolysis: A New Route to Iminosugars via Cyclic Sulfates,International audience,10.1055/s-2002-32967,2002-01-01,0.5820894068069742
Organic Letters,Enantioselective Total Synthesis of (−)-Nardoaristolone B via a Gold(I)-Catalyzed Oxidative Cyclization,"The first enantioselective total synthesis of (-)-nardoaristolone B is accomplished by the implementation of an enantio- and diastereoselective copper(I)-catalyzed conjugate addition/enolate trapping sequence and a gold(I)-catalyzed oxidative cyclization (intermolecular oxidant), employed for the first time in total synthesis.",10.1021/ol503531n,2015-01-07,0.5820888434624869
Tetrahedron,Studies on the synthesis of highly substituted furans: The synthesis of calicogorgins A and C,,10.1016/s0040-4039(97)00074-9,1997-02-01,0.5820769768623472
Tetrahedron,Addition of carbamoylsilane to isatins: Highly efficient synthesis of 3-hydroxy-3-aminocarbonyl-2-oxindoles derivatives,,10.1016/j.tetlet.2017.05.051,2017-05-17,0.5820726767819071
Synlett,Synthesis of the C1-C8 Tetrahydropyranyl Segment of the Antifungal Agent Ambruticin and its C3 Epimer,"All articles of this category The synthesis of the C1-C8 segment ( 2 ) of ambruticin and its C3 epimer ( 9 ), were accomplished starting from the diethyldithioacetal of L-arabinose in 10 and 8 steps (10% and 16% yield) respectively. The synthesis of the C1-C8 segment ( 2 ) of ambruticin and its C3 epimer ( 9 ), were accomplished starting from the diethyldithioacetal of L-arabinose in 10 and 8 steps (10% and 16% yield) respectively.",10.1055/s-1996-5328,1996-01-01,0.5820664487277165
European Journal of Organic Chemistry,Pyrrolizidine Alkaloids by Intramolecular Palladium‐Catalysed Allylic Alkylation: Synthesis of (±)‐Isoretronecanol,"Abstract An efficient and stereoconvergent approach to 3‐substituted hexahydroindol‐2‐one derivatives by palladium‐catalysed intramolecular allylic alkylation has been developed. Subsequently, the straightforward conversion of the hexahydroindol‐2‐one 7d into the alkaloid (±)‐isoretronecanol has been performed. The synthesis entails 11 steps starting from 1,3‐cyclohexadiene, affording the final target in a 29% overall yield. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2004)",10.1002/ejoc.200400135,2004-06-15,0.5820622897348713
Organic Process Research & Development,A Practical Synthesis of Enantiomerically Pure <i>N</i>-Benzyl-α-methyl Benzylamine,Optically pure (R)- and (S)-N -benzyl-α-methyl benzylamine have been prepared on pilot plant scale from benzaldehyde and α-phenyl-ethylamine via palladium-catalyzed hydrogenation of the intermediate ( R )-benzylidene-(1-phenylethyl)amine.,10.1021/op000201n,2000-09-27,0.5820566718609332
Tetrahedron,"Synthesis of [3,5,5,5-2H4]-2-C-methyl-d-erythritol, a substrate designed for the elucidation of the mevalonate independent route for isoprenoid biosynthesis",,10.1016/s0040-4039(99)01769-4,1999-11-01,0.5820525300568234
Journal of Organic Chemistry,Fully Stereocontrolled Syntheses of 3-Oxacarbacyclin and Carbacyclin by the Conjugate Addition-Azoalkene-Asymmetric Olefination Strategy,A fully stereocontrolled synthesis of 3-oxacarbacyclin (3) and a formal synthesis of carbacyclin (2) are described. The syntheses are based on the conjugate addition-azoalkene-asymmetric olefination strategy. Its key features are (1) the stereoselective establishment of the complete omega-side chain of 2 and 3 through conjugate addition of the enantiopure C13-C20 alkenylcopper derivative 10 to the enantiopure C6-C12 bicyclic azoalkene 9 and (2) the 5E-stereoselective construction of the alpha-side chain through a Horner-Wadsworth-Emmons olefination of the bicyclic ketone 7 with the chiral lithium phosphonoacetate 26 with formation of ester E-27. The allylic alcohol 6 serves at late stage as the joint intermediate in the synthesis of 2 and 3.,10.1021/jo060551t,2006-05-17,0.58204903997266
European Journal of Organic Chemistry,"Synthesis of 6‐(4,5‐Dihydrofuran‐2‐yl)‐ and 6‐(Tetrahydrofuran‐2‐yl)purine Bases and Nucleosides","Abstract A novel approach to the synthesis of purine derivatives (bases and nucleosides) bearing 4,5‐dihydrofuran‐2‐yl and tetrahydrofuran‐2‐yl substituents at the 6‐position as partly and fully saturated analogues of biologically active 6‐hetarylpurine nucleosides is reported. Palladium‐catalyzed cross‐coupling reactions of 6‐iodopurines with new (4,5‐dihydrofuran‐2‐yl)zinc chloride ( 1 ) gave 6‐(4,5‐dihydrofuran‐2‐yl)purines in high yields. Their catalytic hydrogenation gave 6‐(tetrahydrofuran‐2‐yl)purines. These modified purine bases and nucleosides did not exhibit any significant cytostatic or anti‐HCV activity.(© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2008)",10.1002/ejoc.200800174,2008-04-15,0.5820445511373014
Synthesis,Stereoselective Synthesis of the Macrocyclic Core of (-)-Salicylihalamides A and B,"Stereoselective synthesis of the macrocyclic core of salicylihalamides A and B is described. The synthetic strategy features stereoselective iodolactonization, Sharpless asymmetric epoxidation, Mitsunobu esterification, and ring-closing metathesis.",10.1055/s-2007-965970,2007-03-27,0.5820436739342165
Organic Letters,An Efficient Synthetic Route to Glycoamino Acid Building Blocks for Glycopeptide Synthesis,"[reaction: see text] Chemical glycopeptide synthesis requires access to gram quantities of glycosylated amino acid building blocks. Hence, the efficiency of synthesis of such building blocks is of great importance. Here, we report a fast and highly efficient synthetic route to Fmoc-protected asparaginyl glycosides from unprotected sugars in three steps with high yields. The glycosylated amino acids were successfully incorporated into target glycopeptides 7 and 8 by standard Fmoc solid-phase peptide synthesis.",10.1021/ol048342n,2004-09-30,0.5820432423719178
Tetrahedron,A site-selective solvolysis of a cyclopropylcarbinyl methanesulfonate ester: a route to oxygenated α-methylene-γ-butyrolactones,,10.1016/s0040-4039(01)82624-1,1974-01-01,0.5820397425289747
Angewandte Chemie International Edition,Synthesis of Angularly Fused Aromatic Compounds from Alkenyl Enediynes by a Tandem Radical Cyclization Process,"Let's get radical: A general synthetic route toward angularly ortho-fused polyaromatic [4]helicenes starting from aryl alkenyl N-substituted cyclic enediynes is described (see scheme; DMSO=dimethyl sulfoxide, Ns=4-nitrobenzenesulfonyl). The process involved a Bergman cyclization (BC) as the key step of an unprecedented tandem radical reaction.",10.1002/anie.201103318,2011-07-21,0.5820384694976687
Journal of the American Chemical Society,Total Synthesis of Thiostrepton. Assembly of Key Building Blocks and Completion of the Synthesis,"The completion of the total synthesis of thiostrepton (1) is described. The synthesis proceeded from key building blocks 2-5, which were assembled into a growing substrate that finally led to the target molecule. Thus, the dehydropiperidine peptide core 2 was, after appropriate manipulation, coupled to the thiazoline-thiazole fragment 3, and the resulting product was advanced to intermediate 11 possessing the thiazoline-thiazole macrocycle. The bis-dehydroalanine tail equivalent 4 and the quinaldic acid fragment 5 were then sequentially incorporated, and the products so obtained were further elaborated to forge the second macrocycle of the molecule. Several roadblocks encountered along the way were systematically investigated and overcome, finally opening the way, through intermediates 20, 32, 44, 45, and 46, to the targeted natural product, 1.",10.1021/ja052934z,2005-07-19,0.5820384276327331
Tetrahedron,An easy three step synthesis of perfluoroalkylated amphetamines,,10.1016/j.tetlet.2004.08.080,2004-09-14,0.5820360343885737
Synlett,"SNAr Reaction/Claisen Rearrangement Approach to 2,4-Diisoprenylxanthones: Total Synthesis of Garcinone A","A total synthesis of garcinone A, a natural xanthone possessing a 2,4-diisoprenylated structure, was accomplished by utilizing a readily available 1,3-difluoroxanthone derivative as the key intermediate through the installation of two isoprenyl side chains by an SNAr reaction with the alkoxide of 1,1-dimethylallyl alcohol followed by a Claisen rearrangement. The strategy also permitted the selective installation of mutually different allylic moieties at the C2 and C4 positions.",10.1055/s-0040-1707819,2020-06-09,0.5820307019947274
Journal of Organic Chemistry,"An Efficient Stereoselective Synthesis of Penaresidin A from (<i>E</i>)-2-Protected Amino-3,4-unsaturated Sulfoxide","An efficient, modular, asymmetric synthesis of penaresidin A is disclosed. A beta-protected amino-gamma,delta-unsaturated sulfoxide was prepared by stereoselective addition of the lithio anion of (R)-methyl p-tolyl sulfoxide to an unsaturated sulfinylimine. The pendant sulfoxide group was used as an intramolecular nucleophile to functionalize an alkene regio- and stereoselectively to furnish a bromohydrin, which was employed as the key intermediate in the preparation of the azetidine subunit of penaresidin A. The stereogenic centers of the side chain were introduced by a regioselective opening of an epoxide. Julia-Kocienski olefination was used to couple the azetidine and side chain subunits. The methodology disclosed herein is also useful for the synthesis of ribo- and arabino-phytosphingosines and compounds possessing the amino alcohol moiety.",10.1021/jo9022638,2009-12-21,0.5820291016271467
Journal of Organic Chemistry,"A Completely Diastereoselective Electrophilic Fluorination of a Chiral, Noncarbohydrate Sugar Ring Precursor:  Application to the Synthesis of Several Novel 2‘-Fluoronucleosides","A new and completely diastereoselective method for the introduction of fluorine into a noncarbohydrate sugar ring precursor has been developed. The use of N -fluorodibenzenesulfonimide ( 5 ) for the electrophilic fluorination of chiral lactone 4, which is derived from l -glutamic acid, yields the key intermediate 6 . This is transformed into an anomeric acetate 8 and is used for the synthesis of a number of novel α-2‘-fluoronucleosides. Since glutamic acid is used as the synthetic starting material, the l enantiomer may also be synthesized simply by using d -glutamic acid. The incorporation of fluorine into the 2‘ position of the nucleoside provides several advantages including acid stability of the anomeric bond and general resistance to oxidative metabolism. Further, fluorine is a close mimic of hydroxyl groups in size and polarity and in its ability to act as a hydrogen bond acceptor. This may aid in the recognition of these nucleosides by the enzymes involved in nucleoside activation.",10.1021/jo9717898,1998-03-05,0.5820267906163402
Journal of Organic Chemistry,"Rhodium-Catalyzed [4 + 2]-Annulation of <i>o</i>-Acylanilines with <i>N</i>-Sulfonyl-1,2,3-triazoles: Synthesis of 3-Aminoquinolines","Efficient synthesis of 3-aminoquinolines has been demonstrated from readily accessible N -sulfonyl-1,2,3-triazoles and o -acylaniline derivatives. This transformation involves the generation of C–C and C–N bonds through insertion of rhodium azavinyl carbenoid into a N–H bond followed by cyclization and aromatization. The important features include good functional group tolerance, synthesis of indoloquinoline, and isolation of N–H-inserted product, a potential intermediate.",10.1021/acs.joc.3c00748,2023-06-23,0.5820248760980085
Tetrahedron,Use of Montmorillonite clay for the synthesis of linear tetrapyrroles and their cyclization to Uroporphyrinogens,,10.1016/s0040-4039(00)60710-4,1994-06-01,0.5820203210624801
Tetrahedron,"Asymmetric allylsilane-mediated carbocyclization: A highly enantiospecific synthesis of (1S, 2S)-(+)-2-methyl-3-cyclopenten-1-ol",,10.1016/s0040-4039(01)81549-5,1984-01-01,0.5820165518341792
Tetrahedron,Synthetic study of aquayamycin. Part 3: First total synthesis,,10.1016/s0040-4039(00)01480-5,2000-10-01,0.5820115630607064
Tetrahedron,"(3R,4S)-3,4,5-Trihydroxy-4-methylpentylphosphonic acid, an isosteric phosphonate analogue of 2-C-methyl-d-erythritol 4-phosphate, a key intermediate in the new pathway for isoprenoid biosynthesis",,10.1016/j.tetlet.2003.11.001,2003-11-22,0.5819968876432752
Organic Letters,A Short Access to the Skeleton of Elisabethin A and Formal Syntheses of Elisapterosin B and Colombiasin A,"A short stereoselective synthesis of the Elisabethin A skeleton 4 is described, which opens a formal access to the diterpenes Elisapterosin B and Colombiasin A as well. Key reactions were an intermolecular endo-selective Diels-Alder reaction to generate the decalin part of the molecule, a chemo- and diastereoselective allylation of an aldehyde with allylzinc, a palladium ene annulation of the cyclopentane ring, and a novel sulfonium ylide induced fragmentation of a polycyclic ketone. Additional insights have been gained for the crucial epimerization at C-2.",10.1021/ol501998y,2014-08-04,0.581992003191757
Journal of Organic Chemistry,Enantioselective Hydrogenation of Diarylmethanimines for Synthesis of Chiral Diarylmethylamines,An enantioselective hydrogenation of N-substituted diarylmethanimines under mild conditions has been first realized by using an iridium catalyst with a chiral f-spiroPhos ligand. This method provides an efficient access to the asymmetric synthesis of a variety of chiral diarylmethylamines and their derivatives with excellent enantioselectivities (up to 99.4% ee) and high turnover numbers (TON up to 4000).,10.1021/acs.joc.6b01273,2016-07-14,0.5819916447443948
Journal of the American Chemical Society,Divergent Total Syntheses of Phragmalin and Khayanolide-Type Limonoids: A Torquoselective Interrupted Nazarov Approach,"The asymmetric and divergent total syntheses of two phragmalin (moluccensins G and H) and two khayanolide-type (krishnolide F and khayseneganin F) limonoids were disclosed, which employed a torquoselective interrupted Nazarov cyclization as the key step. Taken together with a Liebeskind-Srogl coupling, a benzoin condensation, and bidirectional acyloin rearrangements, our strategy would simplify the synthetic design of both phragmalin and khayanolide-type limonoids and facilitate their modular syntheses. Moreover, the described approach also provides additional insights into the biosynthetic relationships between these two distinct skeletons.",10.1021/jacs.4c16265,2025-01-08,0.5819864382513703
Angewandte Chemie International Edition,(Enantio)selective Hydrogen Autotransfer: Ruthenium‐Catalyzed Synthesis of Oxazolidin‐2‐ones from Urea and Diols,"A novel strategy for the synthesis of oxazolidin-2-ones from vicinal diols and urea is described. In this heterocycle synthesis, two different C-O and C-N bonds are sequentially formed in a domino process consisting of nucleophilic substitution and alcohol amination. The use of readily available starting materials and the good atom economy render this process environmentally benign. While this transformation is already highly chemo- and regioselective, we also developed the first asymmetric version of this method using (R)-(+)-MeO-BIPHEP as the chiral ligand.",10.1002/anie.201600698,2016-04-13,0.5819826847085403
Organic Letters,Utilization of Copper-Catalyzed Carboarylation–Ring Closure for the Synthesis of New Oxazoline Derivatives,"A copper-catalyzed carboarylation-ring-closure strategy was used for the modular synthesis of oxazolines via the reaction of 1-aryl- and 1-alkylpropargylamides and diaryliodonium salts. The novel approach enables the efficient, modular synthesis of oxazoline derivatives bearing fully substituted exo double bonds.",10.1021/acs.orglett.5b01860,2015-08-18,0.5819774538522118
Tetrahedron,Improved preparation deoxophylloerythroetioporphyrin (DPEP) and its 15′-methyl derivative from chlorophyll a.,,10.1016/s0040-4039(00)60780-3,1993-03-01,0.581975617852847
Synthesis,Stereoselective Synthesis of Acceptor Stabilized Prostacyclins,"All articles of this category The preparation of acceptor substituted, stabilized prostacyclins is described. In this process use is made of a bulky ester group which additionally lends itself to directing the stereoselectivity of a deconjugation step for the introduction of the exocyclic double bond.",10.1055/s-1993-25822,1993-01-01,0.5819733567051472
Tetrahedron,Synthetic study on dolastatin 16: concise and scalable synthesis of two unusual amino acid units,,10.1016/j.tetlet.2014.11.054,2014-11-20,0.581970799541687
Journal of Organic Chemistry,"Efficient Access to 2-Isobetulinic Acid, 2-Isooleanolic Acid, and 2-Isoursolic Acid","An efficient access to 2-isobetulin, 2-isobetulinic acid, 2-isooleanolic acid, and 2-isoursolic acid has been developed. The key step is a novel one-pot conversion of 2,3-dihydroxy triterpenes to 3-deoxy-2-oxo triterpenes. This method provides a new access to 3-deoxy-2-substituted pentacyclic triterpenes as potential therapeutic agents against metabolic diseases, tumors, and HIV infection.",10.1021/jo801232s,2008-08-19,0.5819608807904236
Journal of Organic Chemistry,Sonogashira Coupling Reactions of Bromomaleimides: Route to Alkyne/<i>cis</i>-Alkene/Alkyl Maleimides: Synthesis of Luffarin X and Cacospongionolide C,Palladium-catalyzed Sonogashira coupling reaction of bromomaleimides with a diverse range of terminal alkynes has been demonstrated to furnish the corresponding alkynylmaleimides in very good yields. This coupling reaction followed by selective reduction of the triple bond to single bond have been utilized as the decisive steps to accomplish the first total synthesis of natural products (±)-luffarin X and (±)-cacospongionolide C.,10.1021/jo2021218,2011-12-02,0.5819558829590836
Journal of Organic Chemistry,On the Synthesis of Protopine Alkaloids,"For the synthesis of protopine alkaloids, we studied a reaction sequence based on a ring enlargement of indeno[2,1-a][3]benzazepines by a singlet oxygen oxygenation, followed by conversion of an amide carbonyl group of the resultant 10-membered keto-lactam to a methylene group, which is the last step for completion of the synthesis. The key substances, indeno[2,1-a][3]benzazepines, were prepared by Bischler-Napieralski cyclization of alkoxy-substituted 1-(2-bromobenzyl)-3-benzazepin-2-ones. Steric effects of the substituents in this synthesis were examined.",10.1021/jo071038y,2007-08-17,0.5819494783303768
Organic Process Research & Development,"Manufacturing Process Development for Belzutifan, Part 1: A Concise Synthesis of the Indanone Starting Material","A four-step synthesis of the indanone core of belzutifan (MK-6482) is described. This route starts from the commodity raw material dihydrocoumarin and was successfully demonstrated on a large scale to produce indanone 11 in the synthesis of belzutifan, an FDA-approved first-in-class therapy for the treatment of patients with certain types of Von Hippel–Lindau disease-associated tumors.",10.1021/acs.oprd.1c00236,2021-11-08,0.5819462443376285
Synlett,A New Synthetic Route to Monosaccharides from Simple Achiral Compounds By Using a Catalytic Asymmetric Aldol Reaction as a Key Step,"All articles of this category A new synthetic route to monosaccharides from simple achiral α,β-unsaturated aldehydes and chloroacetic acid was developed by using the catalytic asymmetric aldol reaction of 1-trimethylsiloxy-1-phenoxy-2-benzyloxyethene with the aldehydes in the presence of a novel chiral catalyst system consisting of tin(II) triflate, a chiral diamine, and tin(II) oxide.",10.1055/s-1993-22649,1993-01-01,0.5819424400623942
Organic Letters,"Asymmetric Synthesis of Substituted Homoallyl Alcohols, Halomethyl Tetrahydrofurans, and Chloro-amino Sulfones from Allyltitanium Sulfoximines and α-Hetero Aldehydes","Asymmetric syntheses of the iodomethyl-substituted bicyclic tetrahydrofuran 22 and the chloro-amino sulfone 30 from the allylic sulfoximine 15 and the alpha-hetero aldehydes 2 and 23, respectively, are described. Further examples for the asymmetric synthesis of chloromethyl tetrahydrofurans and chloro-amino sulfones are given. The synthesis of 30 features as key step the stereoselective Cl-substitution of a hydroxy group under neighboring group participation by an aminosulfoxonium group which is converted to a sulfonyl group. [reaction: see text].",10.1021/ol0627606,2007-01-17,0.5819422864244037
Organic Letters,"Synthesis of 3,3-Spiroindolines via FeCl<sub>3</sub>-Mediated Cyclization of Aryl- or Alkene-Containing 3-Substituted N–Ac Indoles","We report the cyclization of 3-substituted N-acetylindoles for the straightforward synthesis of 3,3-spiroindolines via the Friedel-Crafts reaction of an appended aryl group or the formal [2 + 2] cycloaddition of an appended alkene. Our strategy involves an Umpolung of the C2═C3 bond of the indole nucleus during FeCl3-mediated hydroarylation or annulation reactions.",10.1021/acs.orglett.6b00174,2016-03-25,0.5819414685033322
European Journal of Organic Chemistry,Structure Elucidation and Total Synthesis of Altenuic Acid III and Studies towards the Total Synthesis of Altenuic Acid II,"Abstract The structure of the Alternaria mycotoxin altenuic acid III was elucidated by NMR spectroscopic analysis of an authentic sample, and was confirmed by total synthesis. This compound is not a resorcylic acid lactone but a resorcylic acid substituted with a butenolide, and thus is the first member of a new class of alternaria toxins. For the total synthesis, a short and efficient access to halogenated butenolides bearing acetal‐protected side‐chains was carried out. Suzuki coupling of these butenolides with a highly functionalized boronate gave rise to a precursor of the natural product in high yield. The side‐chain was completed by deprotection and subsequent oxidation. An unexpected cascade reaction leading to tricyclic butenolides was discovered during optimization of the deprotection protocol. Cleavage of the acetal protecting group gave altenuic acid III. Furthermore, a synthetic study towards altenuic acid II, a compound with a characteristic spirolactone structure, is described. It was planned to construct the spirocyclic lactone by using an intramolecular Michael‐type addition of an aromatic carboxylate group to a butenolide moiety, but this approach was not successful. While testing the feasibility of this concept, a new and mild protocol for the well‐known Pinner reaction in the presence of Lewis acids was discovered.",10.1002/ejoc.201300879,2013-08-16,0.5819377090878134
Organic Letters,Synthesis of the Tricyclic Ring Structure of Daphnanes via Intramolecular [4 + 3] Cycloaddition/SmI<sub>2</sub>-Pinacol Coupling,"A synthetic approach toward the tricyclic 5,7,6-membered ring structure of daphnane-family natural products is described. An intramolecular [4 + 3] cycloaddition reaction of furan with an oxypentadienyl cation constructed the oxa-bridged bicyclic structure in a stereoselective fashion. Structural analysis revealed that the desired exo isomer was predominantly acquired through epimerization. Finally, formation of the five-membered ring was achieved through SmI2-mediated pinacol coupling.",10.1021/acs.orglett.5b01054,2015-05-21,0.5819347749223183
Journal of Organic Chemistry,Oxytrofalcatin Puzzle: Total Synthesis and Structural Revision of Oxytrofalcatins B and C,"The previously reported structures of oxytrofalcatins B and C possess a benzoyl indole core. However, following synthesis and NMR comparison of both the proposed structure and the synthesized oxazole, we have revised the structure of oxytrofalcatins B and C as oxazoles. The synthetic route developed herein can further our understanding of the biosynthetic pathways that govern the production of natural 2,5-diaryloxazoles.",10.1021/acs.joc.3c00691,2023-07-11,0.5819303214244707
Tetrahedron,"Highly diastereoselective reaction of a chiral, non-racemic amide enolate with (S)-glycidyl tosylate. Synthesis of the orally active HIV-1 protease inhibitor L-735,524",,10.1016/s0040-4039(00)75787-x,1994-01-01,0.5819277716655533
Tetrahedron,The synthesis of a chiral receptor molecule containing three carbohydrate residues within a 20-crown-6 constitution,,10.1016/s0040-4039(01)86369-3,1979-01-01,0.5819267208531153
Tetrahedron,A fast and efficient method for the preparation of the 5-lipoxygenase inhibitor myxochelin A,,10.1016/j.tetlet.2016.02.047,2016-02-14,0.5819266581782989
Organic Letters,"<i>N</i>-Oxides of Adenosine-Type Nucleosides Undergo Pyrimidine Ring Opening and Closure To Give 5-Amino-4-(1,2,4-oxadiazol-3-yl)imidazole Derivatives","Treatment of acylated adenosine N-oxides with carboxylic anhydrides and thiophenol resulted in pyrimidine ring opening followed by exocyclic ring closure. Ammonolysis gave 5-amino-4-(5-substituted-1,2,4-oxadiazol-3-yl)-1-(beta-d-ribofuranosyl)imidazole derivatives, whereas iodine in methanol selectively unmasked the 5-amino group. Related flexible nucleoside analogues can be prepared from adenine-type precursors.",10.1021/ol061715v,2006-08-31,0.581921147725837
European Journal of Organic Chemistry,Synthesis of 2-Fluoro Analogues of Frontalin,"The synthesis of enantiomerically and diastereomerically pure (−)-(1R,2R,5R)- and (−)-(1R,2S,5R)-2-fluoro frontalin (7) starting from (+)-(1S)-menthyl-(R)-toluene-4-sulfinate, methylmagnesium bromide, methyl fluoroacetate, 4-pentenyl bromide and diazomethane is described. The absolute stereochemistry was unambiguously determined by X-ray analysis of (+)-(1S,2R,5S,RS)-5, an intermediate in the synthesis of the enantiomeric (+)-(1S,2R,5S)-2-fluoro frontalin (7).",10.1002/(sici)1099-0690(200004)2000:8<1387::aid-ejoc1387>3.0.co;2-g,2000-04-01,0.5819205904938681
Synlett,A New Synthesis of Benzo[<i>b</i>]acridones,"A novel and efficient route for the synthesis of new benzo[b]acridones has been described. It involves the Diels-Alder reaction of N-substituted-4-quinolone-3-carbaldehyde with ortho-benzoquinodimethanes giving benzo[b]-1,6,6a,12a-tetrahydroacridones, which are the result of a cycloaddition reaction followed by an in situ deformylation. The oxidation of these tetrahydroacridones in dimethyl sulfoxide using a catalytic amount of iodine gives the new benzo[b]acridone derivatives. It was demonstrated that the ­cycloaddition reaction is only efficient if an electron-withdrawing N-protecting group is present.",10.1055/s-0028-1087372,2008-11-26,0.581920088571717
Tetrahedron,A simple approach for the synthesis of azocine alkaloids: The total synthesis of megallanesine,,10.1016/j.tetlet.2018.05.055,2018-05-21,0.5819150516435388
European Journal of Organic Chemistry,A Practical Synthesis of Thiopyrylium Tetrafluoroborate from Ethyl Vinyl Sulfide,"A new, efficient synthesis of thiopyrylium tetrafluoroborate (C5H5S+ BF4−) is described. It is based on the three-step sequence ethyl vinyl sulfide → propargyl vinyl sulfide → 2H-thiopyran → C5H5S+ BF4− in an overall yield of 54%. Preparations of C5H5S+ BPh4−, C5H5S+ I−, and C5H5S+ CF3SO3− (TfO−) are also described. The latter is the subject of the first X-ray single crystal structure determination of the thiopyrylium ion.",10.1002/1099-0690(200107)2001:13<2477::aid-ejoc2477>3.0.co;2-h,2001-07-01,0.5819133020609065
Journal of Organic Chemistry,Stereoselective Preparation of a Cyclopentane-Based NK1 Receptor Antagonist Bearing an Unsymmetrically Substituted Sec−Sec Ether,A highly efficient synthesis of the potent and selective NK-1 receptor antagonist 1 is described. The key transformation involved the etherification reaction between cyclopentanol 12 and chiral imidate 30 which was catalyzed by HBF4 to initially give ether 14 as a 17:1 mixture of diastereomers and in 75% combined yield. The diastereoselectivity was upgraded to 109:1 by crystallization of the triethylamine solvate 44 which was isolated in 54% yield from 12. Mechanistic studies confirmed that the etherification reaction proceeds through an unprecedented S(N)2 reaction pathway under typical S(N)1 reaction conditions.,10.1021/jo061268x,2006-08-24,0.5819129778653495
Synthesis,"A New Approach to the Synthesis of 3-Substituted 4-(Diethoxyphosphoryl)isoxazoles from 3-Azidoalka-1,3-dienylphosphonates","New 3-azidoalka-1,3-dienylphosphonates were synthesized by a convenient and efficient method. These compounds are useful as intermediates in the preparation of 3-(3-aryl-4,5-di­hydroisoxazol-5-yl)- and 3-alkenyl-4-(diethoxyphosphoryl)isoxazoles.",10.1055/s-0029-1216962,2009-08-21,0.5819057390137063
Organic Letters,"<i>trans</i>-6-Aminocyclohept-3-enols, a New Designed Polyfunctionalized Chiral Building Block for the Asymmetric Synthesis of 2-Substituted-4-hydroxypiperidines","trans-6-Aminocyclohept-3-enols 18 and ent-18 are new designed polyfunctionalized chiral building blocks for piperidine alkaloids synthesis and are prepared in high yields from the enzymatically derived cyclohept-3-ene-1,6-diol monoacetate (-)-8. Efficient highly enantioselective syntheses of cis-4-hydroxypipecolic acid (1) and piperidines 3 and 4, in both enantiomeric forms, are described. [reaction: see text]",10.1021/ol025683x,2002-03-23,0.5819002320136014
Synthesis,A New Synthesis of Substituted Cyclopentenones by Olefin Cyclization Initiated by Pummerer Reaction Intermediates,On prepare une serie d'enones monocycliques et bicycliques par cyclisation de methyl (oxo-2 acenyl) sulfoxydes,10.1055/s-1985-31290,1985-01-01,0.5818969032170048
Synlett,First Enantiospecific Synthesis of Antileishmanial 12-Deoxyroyleanone from Abietic Acid,"12-Deoxyroyleanone (1), an abietane diterpenoid with appreciable antileishmanial activity, has been efficiently synthesized from abietic acid (10; 11 steps for a 25% overall yield).",10.1055/s-2004-835625,2004-10-22,0.5818878612454521
Organic Letters,"Total Synthesis of Pactalactam, an Imidazolidinone-Type Pactamycin Analogue","The first total synthesis of pactalactam was accomplished using substrate-controlled stereoselective aziridination and regioselective aziridine ring-opening to construct three continuous amino groups on an octasubstituted cyclopentane core. The cyclopentane framework was obtained by ring-closing metathesis and aldol coupling using a l-threonine-derived oxazoline compound. Cyclic urea formation, m-acetylphenyl group introduction by Chan-Lam coupling, and primary alcohol-selective acylation yielded the reported pactalactam structure. The presence of pactalactam in the fermentation broth of pactamycin-producing bacteria was also confirmed.",10.1021/acs.orglett.9b00905,2019-05-06,0.5818720236359469
Tetrahedron,"Palladium-catalyzed intramolecular 1,4-dialkoxylation of cyclohexadienes: An efficient route to highly stereocontrolled oxygen heterocycles",,10.1016/s0040-4039(97)10735-3,1998-03-01,0.5818676072047868
Tetrahedron,A new entry to the synthesis of β-hydroxytyrosines via a novel benzylic hydroxylation,,10.1016/s0040-4039(00)80712-1,1988-01-01,0.5818596164425739
Angewandte Chemie International Edition,Biomimetic Synthesis of Grossularines‐1,"Like a sea squirt: An efficient biomimetic synthesis of the antitumor α-carboline marine alkaloids grossularine-1 (1) and N,N-didesmethylgrossularine-1 (2) is based on a novel oxidative dimerization of 2-amino-4-(3-indolyl)imidazole.",10.1002/anie.200500055,2005-04-28,0.5818572890085826
Tetrahedron,"A short and efficient route from tetrahydrothiophene to thieno[2,3-d][1,3,2]dithiazolium salts",,10.1016/j.tetlet.2012.05.043,2012-05-16,0.581848327891931
Tetrahedron,Short and practical enantioselective synthesis of linezolid and eperezolid via proline-catalyzed asymmetric α-aminooxylation,,10.1016/j.tetlet.2006.07.065,2006-08-08,0.5818477212372809
Tetrahedron,"Diastereoselective, large scale synthesis of β-amino acids via asymmetric enamide hydrogenation as α2δ ligands for the treatment of generalized anxiety disorder and insomnia",,10.1016/j.tetlet.2009.08.111,2009-09-03,0.5818472078076284
Organic Letters,Total Synthesis and Biological Activity of the Arachidonic Acid Metabolite Hemiketal E<sub>2</sub>,"The total synthesis of hemiketal E 2 (HKE 2 ) has been accomplished using a gold(I)-mediated cycloisomerization followed by oxidation of the enol ether product to introduce a unique keto-hemiketal, the core structure of HKE 2 . Synthetic hemiketal E 2 reproduced biosynthetically derived HKE 2 in the inhibition of human platelet aggregation.",10.1021/acs.orglett.8b01578,2018-06-19,0.5818450503708118
Synlett,A Rapid Synthesis of (-)-Tetrahydrolipstatin,All articles of this category (-)-Tetrahydrolipstatin ( 1 ) has been synthesised starting from diketene using photoalkylation and β-lactone enolate alkylation as key steps. tetrahydrolipstatin - photochemistry - diketene - β-lactone enolates,10.1055/s-2000-6448,2000-01-01,0.5818446883444738
Tetrahedron,An improved total synthesis of UDP-N-acetyl-muramic acid,,10.1016/j.tetlet.2007.04.098,2007-04-23,0.5818415107913869
Tetrahedron,"Enantioselective preparation of 1-benzyloxy-3-methyl-6-heptene-2,4-diols: Total synthesis of (+)-prelactone C",,10.1016/s0040-4039(97)01042-3,1997-07-01,0.5818336434758283
Journal of Organic Chemistry,Expeditious Synthesis of Tri- and Tetrahydroxyazepanes from <scp>d</scp>-(−)-Quinic Acid as Potent Glycosidase Inhibitors,"Several new stereoisomers of 3,4,6-trihydroxyazepanes and 7-hydroxymethyl-3,4,5-trihydroxyazepanes as well as known 3,4,5-trihydroxyazepanes were synthesized as potent glycosidase inhibitors from D-(-)-quinic acid in an efficient manner. The key step employs dihydroxylation of protected chiral 1,4,5-cyclohex-2-enetriols under RuCl3/NaIO4/phosphate buffer (pH 7) condition, followed by reductive amino cyclization. We found the choice of an appropriate protecting group to C1-OH of chiral 1,4,5-cyclohex-2-enetriols would increase the yields of cyclization. The preliminary biological data indicate some of these azepanes possess potent inhibition against alpha-mannosidase and alpha-fucosidase.",10.1021/jo070058x,2007-05-01,0.5818308972365707
Synthesis,"Pheromone Synthesis via Organoboranes: A Simple Synthesis of (<i>Z</i>)-5-Undecen-2-one, A Ketone from the Pedal Gland of the Bontebok (<i>Damaliscus dorcas dorcas</i>)",,10.1055/s-1984-30817,1984-01-01,0.5818213400270088
Organic Letters,Biomimetic Total Syntheses of Ergot Alkaloids via Decarboxylative Giese Coupling,"Biomimetic total syntheses of Festuclavine and Pyroclavine were achieved by a sequential radical coupling. The key steps include intramolecular decarboxylative Giese reaction to form the central C ring and 4-nitrobenzenesulfonyl (Ns)-directed indole C4–H olefination to introduce the indole C4 component. In addition, D-ring formation was completed by decarboxylative alkenylation and intramolecular S N 2 reaction.",10.1021/acs.orglett.0c03867,2020-12-23,0.5818170373162264
Tetrahedron,A highly efficient total synthesis of (R)-(+)-muscopyridine by intramolecular [4+2] cycloaddition of bisketene,,10.1016/j.tetlet.2007.12.112,2007-12-26,0.5818156111033268
Synthesis,Radical-Mediated Synthesis of Racemic Deoxypodophyllotoxin and Related Lignans,An approach for the synthesis of lignans related to the podophyllotoxin family is reported. The key reaction is a highly dia­stereoselective iodoacetal cyclization under iodine atom transfer conditions followed by a homolytic aromatic substitution. The second aromatic ring is introduced at a later stage via addition of aryllithium to an aryl ketone. A novel and very mild method for the deoxygenation of the intermediate tertiary benzylic alcohols is described.,10.1055/s-2005-865358,2005-01-01,0.5818142056504949
Organic Letters,First Gram-Scale Synthesis of a Heparin-Related Dodecasaccharide,"The first example of a gram-scale synthesis of a structurally defined, heparin-related dodecasaccharide is reported. An iterative 14-step process using an iduronate donor disaccharide delivers >1g quantities of the dodecasaccharide sequence [GlcNS-IdoA2S](6)-OMe in 15% overall yield from the reducing terminal disaccharide, a 2 orders of magnitude increase in scale for access to synthetic heparanoid dodecasaccharide mimetics. The synthesis also delivers multigram amounts of the protected oligosaccharides from tetra- through to dodecasaccharide.",10.1021/ol303112y,2012-12-14,0.5818126969078559
Organic Letters,Asymmetric Synthesis of (−)-Tetrahydrolipstatin:  An <i>anti</i>-Aldol-Based Strategy,"A stereoselective synthesis of (-)-tetrahydrolipstatin is described. The synthesis involves an asymmetric ester derived titanium enolate anti-aldol reaction, a nitro-aldol reaction to append the C-2' C(11) side chain, and a diastereoselective reduction of a beta-hydroxy ketone to an anti-1,3-diol functionality followed by its elaboration to (-)-tetrahydrolipstatin.",10.1021/ol000070a,2000-07-20,0.5818112090266042
Organic Letters,Synthetic Approach to Wortmannilactone C,"A diastereomer of wortmannilactone C has been synthesized according to a convergent and versatile strategy from tert-butyl 3-hydroxypropanoate and ethyl (R)-3-hydroxybutanoate. The key steps are a Liebeskind cross-coupling and a Horner-Wadsworth-Emmons (HWE) reaction to construct the macrolactone. The stereogenic centers at C9, C11, and C21 were controlled by enantioselective allyltitanations, and the C19 stereocenter was controlled by using a Noyori reduction of an acetylenic ketone.",10.1021/ol5036112,2015-01-29,0.5818112060950709
Organic Letters,Selective endo and exo Iodocyclizations in the Synthesis of Quinolines and Indoles,"[reaction: see text] A simple, efficient method for a divergent synthesis of indoles, quinolines, and quinolinones using a highly selective endo/exo iodocyclization procedure is described.",10.1021/ol052518j,2005-12-23,0.5818109754574862
Organic Letters,A Cyclopropanol-Based Strategy for Subunit Coupling:  Total Synthesis of (+)-Spirolaxine Methyl Ether,A strategy for ketone synthesis with cyclopropanols as intermediates and its application to (+)-spirolaxine methyl ether is described. The synthesis also features an application of Fu's alkyl-alkyl Suzuki coupling.,10.1021/ol0710111,2007-06-09,0.5818082245081254
Synlett,A Novel Synthetic Approach towards Chiral QUINAP via Diastereomeric Sulfoxide Intermediates,"A novel enantioselective synthesis of chiral QUINAP is described. Hereby, the separation of the diastereomers was achieved by the preparation and simple chromatographic separation of chiral sulfoxide intermediates. Subsequent sulfoxide-lithium exchange, quenching with Ph2PCl and sulfur, then desulfurisation with Raney-Ni provided (R)- and (S)-QUINAP in 54-56% overall yield.",10.1055/s-2007-991047,2007-09-25,0.5818076247800995
Synlett,"Functionalized 2,5-Disubstituted Benzazepines: Stereoselective Synthesis of 3-Methyl-5-phenyl-2,3,4,5-tetrahydro-1<i>H</i>-3-benzazepine-2-carbonitrile and Related Derivatives","A stereoselective synthesis of 2-carbonitrile and 2-aminomethyl-substituted 5-phenylbenzazepine derivatives was developed starting from [4-hydroxy-3-(methyloxy)phenyl]acetic acid. The key step in the synthesis is a stereoselective addition of cyanide to 3-methyl-1-phenyl-2,3-dihydro-1H-3-benzazepine (4) to give a 15:1 trans/cis mixture of 2-carbonitrile-5-phenyl benzazepine dia­stereomers 5a/5b in 83% yield. The stereochemistry of the major product was deduced by 1H NMR NOESY analysis. The carbonitrile diastereomers could be separated and further manipulated by reduction to the corresponding aminomethyl derivatives 3a and 3b in a stereoselective manner. The aminomethyl benzazepine template 3 has potential to serve as a handle for the synthesis of a variety of derivatives modified at the 2-position of the benzazepine scaffold, as illustrated by an acylation of the primary amine of 3 ­followed by mild deprotection of the 7-phenol functionality.",10.1055/s-2004-825618,2004-01-01,0.5818053618903827
Synlett,An Approach to the Tricyclic Lactone Core of Brasoside and Related Natural Products,"A one-pot iodine atom transfer/cyclisation and intermolecular olefination is described for the efficient, stereoselective construction of bicyclic lactone intermediates en route to compound 21, a potential precursor to the brasoside (1) skeleton.",10.1055/s-2004-835637,2004-11-08,0.581804387823154
Organic Letters,Convergent Stereoselective Synthesis of the Visual Pigment A2E,"[chemical reaction: see text]. A stereoselective total synthesis of the visual pigment A2E has been achieved with use of palladium-catalyzed cross-coupling reactions in all key steps: a regioselective Suzuki or Negishi coupling of 2,4-dibromopyridine, a Sonogashira reaction, and a double Stille cross-coupling to complete the bispolyenyl skeleton.",10.1021/ol052512u,2005-11-15,0.5818034170981164
Journal of Organic Chemistry,An Improved Synthesis of a Ketone Catalyst for Asymmetric Epoxidation of Olefins,An efficient synthesis of a ketone catalyst for asymmetric epoxidation of olefins from D-glucose in six steps is described.,10.1021/jo0206770,2003-05-15,0.5818005872215939
European Journal of Organic Chemistry,Synthetic Studies on Alotamide A: Construction of <i>N</i>‐Demethylalotamide A,"Abstract Several approaches to the synthesis of cyclodepsipeptide natural product alotamide A are described, eventually affording a very advanced N ‐demethylated analogue of the targeted natural product. The difficulties found in our endeavors on the synthesis of alotamide A have allowed us to gather some valuable information regarding the most convenient synthetic step for each key transformation. The intramolecular Csp 2 −Csp 2 Stille cross‐coupling and the macrolactam formation were found to be reliable protocols for the final construction of the alotamide A skeleton.",10.1002/ejoc.202101104,2021-10-24,0.5817979669698952
Tetrahedron,Synthesis of aminomethyl substituted silacyclohexanes from divinylsilanes: An unusually selective sequence,,10.1016/s0040-4039(99)00678-4,1999-05-01,0.5817908135547571
Organic Process Research & Development,Correction to “Evolution of the Synthesis Route for CC-99677: From Discovery Towards Commercialization”,,10.1021/acs.oprd.5c00501,2025-12-31,0.5817898802715011
Tetrahedron,"Novel intramolecular cyclization of 2-(buta-1,3-dienyl)-3-methylpyrazines and 3-(buta-1,3-dienyl)-4-methyl-1,2,5-oxadiazoles into 5H-cycloheptapyrazines and 4H-cyclohepta-1,2,5-oxadiazoles",,10.1016/j.tetlet.2004.03.123,2004-04-21,0.5817873908421192
Journal of Organic Chemistry,Diversity-Oriented Synthesis of Heterocycles: Al(OTf)<sub>3</sub>-Promoted Cascade Cyclization and Ionic Hydrogenation,"An efficient and facile method has been developed for the diversity-oriented synthesis of heterocycles. Hexahydrophenoxazines, tetrahydroquinolines, indolines, hexahydrocarbazoles, and lactones were conducted via Al(OTf) 3 -promoted cascade cyclization and ionic hydrogenation. Furthermore, this protocol was utilized to smoothly prepare piracetam and its key intermediate as well.",10.1021/acs.joc.7b02894,2018-01-04,0.5817845372534213
Journal of Organic Chemistry,"Chemistry of Quinoline-5,8-diones","Room-temperature acid-catalyzed methanolysis of 7-formamido-, 7-acetamido-, or 7-isobutyramido-2-methylquinoline-5,8-diones ( 3, 4, 5 ) gives good to excellent yields of 7-amino-2-methylquinoline-5,8-dione ( 6 ). Simple methods for the synthesis of novel 7-amino-6-chloro-2-methylquinoline-5,8-dione ( 7 ), 7-alkoxy-2-methylquinoline-5,8-diones ( 9 − 11 ), and quinoline quinols ( 12, 13 ) are described, and the corresponding mechanisms are discussed. The replacement of an amino group on a quinone ring by alkoxy groups to produce 9 − 11 is reported for the first time and offers easy routes for the syntheses of these alkoxy derivatives. Also, the 1,2-addition of an ethyl group (rather than the expected 1,4-addition of a cyano group) of the reagent diethylaluminum cyanide to a quinolinedione is another novel reaction for the efficient preparation of quinoline quinols 12 and 13 . An easy transformation of amino compound 6 to its acetamido derivative 4 is also described.",10.1021/jo971823i,1998-01-01,0.5817845115758931
Organic Letters,Total Synthesis of Diptoindonesin G via a Highly Efficient Domino Cyclodehydration/Intramolecular Friedel−Crafts Acylation/Regioselective Demethylation Sequence,"A highly efficient total synthesis of diptoindonesin G is described employing a domino dehydrative cyclization/intramolecular Friedel-Crafts acylation/regioselective demethylation reaction of aryloxyketone 7 by the action of BCl(3) wherein the tetracyclic 6H-anthra[1,9-bc]furan-6-one skeleton was constructed via the 3-arylbenzofuran in a one-pot manner. This is the first example of the strategic combination of these three reactions in a cascade fashion. The routes presented here allow for direct access to diptoindonesin G and its analogues.",10.1021/ol102322g,2010-10-29,0.581782287687916
Synlett,Synthesis of two Diastereoisomers of A/B Fragment of Ciguatoxin,All articles of this category Synthesis of 2 diastereoisomers of A/B fragments of ciguatoxin was achieved by connecting a hexose and 2 pentose derivatives with silylacetylene. The key steps are the cationic cyclization and reductive decomplexation of the acetylene biscobalthexacarbonyl complex. Two diastereoisomers were synthesized from D-glucose and D-arabinose or L-xylose derivatives as partial model compounds for the A/B ring of ciguatoxin.,10.1055/s-1995-5225,1995-11-01,0.5817804922845381
Organic Process Research & Development,Synthesis of Trelagliptin Succinate,"An improved process for the synthesis of antidiabetic drug trelagliptin succinate through unprotected ( R )-3-aminopiperidine was described. The impurity profile with different conditions of the key substitution was illustrated, and then the best reaction condition was identified. The optimizations also included the bromination of 4-fluoro-2-methylbenzonitrile so that the process became efficient and concise.",10.1021/acs.oprd.7b00013,2017-03-09,0.5817795191208752
Organic Letters,Putative Biomimetic Route to 8-Oxabicyclo[3.2.1]octane Motif from a Humulene Sesquiterpenoid Zerumbone,"An approach to expand the diversity of terpenes to novel polycyclic skeletons with contiguous stereogenic centers is described. An unprecedented 8-oxabicyclo[3.2.1]octane motif was obtained in quantitative yield by photoirradiation of zerumbone in the presence of a catalytic amount of Lewis acid. The vital role of light in the isomerization of double bonds in zerumbone, which ensued cyclization via tertiary carbocation intermediate, emulates a biosynthetic route. Synthetic diversification of the phototransformed product afforded epoxy derivatives with up to seven contiguous stereogenic centers and eight-member ring fused tricyclic motifs. The present work sheds light on the possible role of UV irradiation in the biosynthesis of oxo-bridged tricyclic structures from polyene terpenes.",10.1021/acs.orglett.0c02220,2020-08-07,0.5817686161313341
Tetrahedron,Synthesis of the human aldose reductase inhibitor rubrolide L,,10.1016/j.tetlet.2010.06.129,2010-07-04,0.5817637151946354
Organic Letters,Total Synthesis of a Structurally Complex Tetrasaccharide Repeating Unit of <i>Vibrio cholerae</i> O43,"Herein we report the first total synthesis of a densely functionalized tetrasaccharide repeating unit of Vibrio cholerae O43, which contains rare deoxy amino sugars d -quinovosamine and d -viosamine attached with the rare amino acid N -acetyl- l -allothreonine. Synthesis of orthogonally protected rare sugars and unnatural amino acid building blocks, stereoselective construction of three consecutive 1,2- cis glycosidic linkages, amide coupling, and the presence of five nitrogen atoms dispersed over four sugar units as well as the carboxylic acid functionality make the total synthesis a formidable task.",10.1021/acs.orglett.3c02430,2023-08-21,0.5817599169222852
Organic Letters,Synthesis of Multisubstituted Arylnitriles <i>via</i> Tf<sub>2</sub>O-Mediated Benzannulation of Enaminones with Acylacetonitriles,"A novel and efficient method for the synthesis of multisubstituted arylnitriles via Tf 2 O-mediated [3 + 2 + 1] benzannulation of enaminones and acylacetonitriles has been developed. This reaction proceeds under mild conditions with excellent functional group compatibility. Mechanistic studies have revealed that the cyclization involves two consecutive nucleophilic additions, followed by a cascade Knoevenagel condensation and aromatization. Additionally, trifluoromethanesulfonate 6 has been identified as a crucial intermediate in this process.",10.1021/acs.orglett.5c00261,2025-03-03,0.5817505193527024
Synthesis,"A Short, Multigram Synthesis of 1,8-Diaminocarbazole","A one-pot, multigram, and chromatography-free procedure has been developed for the preparation of 1,8-diamino-9H-carbazole, a versatile synthon for the synthesis of anion receptors and conducting polymers. The synthesis consists of a one-pot, palladium-catalyzed reduction of nitro groups and hydrodechlorination of 3,6-dichloro-1,8-dinitrocarbazole, which in turn can be easily produced on a large scale from inexpensive carbazole.",10.1055/s-0030-1258191,2010-08-04,0.5817443992512665
Tetrahedron,Synthetic studies on the immunosuppressive agent FK-506: Enantioselective synthesis of a C22C34 fragment,,10.1016/s0040-4039(97)10532-9,1998-01-01,0.5817426536761742
Tetrahedron,Synthesis of novel glycolipids derived from glycopyranosyl azides and N-(β-glycopyranosyl)azidoacetamides,,10.1016/j.tetlet.2008.08.073,2008-08-25,0.5817419772140272
Journal of Organic Chemistry,"Total Syntheses of (−)-α-Kainic Acid and (+)-α-Allokainic Acid via Stereoselective C−H Insertion and Efficient 3,4-Stereocontrol","Reported herein is a novel approach to the total syntheses of (-)-alpha-kainic acid and (+)-alpha-allokainic acid, where the stereochemistries on C(2), C(3), and C(4) of the pyrrolidine core were introduced efficiently and selectively. A regio- and stereoselective C-H insertion reaction was utilized to prepare the gamma-lactam as an intermediate. A Michael-type cyclization of phenylsulfone with a conjugated acetylenic ketone was developed to prepare the tricyclic ketone as a key intermediate for (-)-alpha-kainic acid. Subsequently, a stereoselective dephenylsulfonylation was carried out successfully to secure the cis relationship at C(3) and C(4) centers. An unprecedented acetylation on the phenylsulfone, followed by a stereoselective dephenylsulfonylation, secured the trans relationship at C(3) and C(4) centers in (+)-alpha-allokainic acid.",10.1021/jo701988j,2007-11-29,0.5817385302576032
Organic Letters,Synthetic Studies toward the C14–C29 Fragment of Mirabalin,"A convergent synthesis of one isomer of the C14-C29 fragment of mirabalin is disclosed. The key steps include a Marshall allenylation, a Mukaiyama aldol reaction and a Crimmins aldolization, which allow the control of 10 out of 25 stereogenic centers present in the molecule.",10.1021/acs.orglett.6b02162,2016-09-07,0.5817330039897164
Organic Process Research & Development,Practical Asymmetric Synthesis of Trifluoromethyl-Containing Aminoester Using a Modified Davis Protocol,"Practical synthesis of aminoester 1 starting from 1,1,1-trifluoro-3-iodopropane is presented. Use of Ti(O i -Pr) 4 as a Lewis acid for condensation of intermediate aldehyde 8 with ( S )-(+)- p -toluenesulfinamide was found to be critical. Conditions for a reproducible and high-yielding Wittig reaction of aldehyde hydrate with phosphorus ylide 4, that appear to have general applicability, are described.",10.1021/op700259d,2008-05-01,0.5817312060843927
Organic Letters,Practical Synthesis of Kainoids: A New Chemical Probe Precursor and a Fluorescent Probe,"A practical total synthesis of kainoid MFPA (5) was achieved in only six steps, via a novel Ni-catalyst-mediated asymmetric conjugate addition reaction. Furthermore, a fluorescein-based fluorescent ionotropic glutamate receptor probe 28 was efficiently synthesized from a precursor derived from a synthetic intermediate of 5.",10.1021/ol403434e,2014-01-07,0.5817293205519835
Journal of Organic Chemistry,"Enantiospecific Syntheses of (+)-Crotepoxide, (+)-Boesenoxide, (+)-β-Senepoxide, (+)-Pipoxide Acetate, (−)-<i>iso</i>-Crotepoxide, (−)-Senepoxide, and (−)-Tingtanoxide from (−)-Quinic Acid<sup>1</sup>","A convenient strategy that is ideally suited for the construction of all the naturally occurring cyclohexane diepoxides and cyclohexene epoxides is described. The key intermediate 12, a 1,3-cyclohexadiene, has been prepared from (−)-quinic acid in 11 steps with 18% overall yield. Singlet oxygen photooxygenation of the 1,3-cyclohexadiene followed by rearrangement of the resultant endoperoxides with either cobalt- meso -tetraphenylporphyrin or trimethyl phosphite afforded enantiopure (+)-crotepoxide, (+)-boesenoxide, and (−)- iso -crotepoxide or (−)-senepoxide, (+)-β-senepoxide, (+)-pipoxide acetate, and (−)-tingtanoxide, respectively.",10.1021/jo970907o,1998-02-18,0.5817237517382078
European Journal of Organic Chemistry,Efficient Synthesis of 3-Deoxy-D-arabino-2-heptulosonate (DAH) and -D-gluco-2-heptulosonate by a Two-Carbon Chain Elongation of D-Arabinose,"Reaction of α-lithiated methyl glyoxylate diethyl mercaptal (3) with 2,3,5-tri-O-benzyl-D-arabinose (2) stereoselectively afforded the D-gluco-2-heptulosonate derivative 4. Mercaptal cleavage led to the corresponding pyranose 5a which could be directly transformed into unprotected D-gluco-2-heptulosonic acid (1a), one of the target molecules. Deoxygenation of 5a at C-3 could also be readily accomplished as its 3-hydroxy group is unprotected. Thus, the second target molecule, 1b, was obtained in just a few steps.",10.1002/1099-0690(20021)2002:1<57::aid-ejoc57>3.0.co;2-h,2002-01-01,0.5817233528257403
Synthesis,Synthesis of New Dehydro 2-Azatryptophans and Derivatives via Heck Cross-Coupling Reactions of 3-Iodoindazoles with Methyl 2-(Acetylamino)acrylate,This paper describes the Heck cross-coupling reaction of 3-iodoindazoles with methyl 2-(acetylamino)acrylate as a general route to new dehydro 2-azatryptophans and protected amino acid derivatives after catalytic hydrogenation.,10.1055/s-2006-950242,2006-10-01,0.5817233042127546
Angewandte Chemie International Edition,Palladium‐Catalyzed Decarboxylative Vinylation of Potassium Nitrophenyl Acetate: Application to the Total Synthesis of (±)‐Goniomitine,"Merge and divert: The natural product (±)-goniomitine was synthesized by a method featuring two key steps: 1) fragment coupling to a functionalized cyclopentene by a novel palladium-catalyzed decarboxylative vinylation reaction and 2) an unprecedented one-pot integrated oxidation/reduction/cyclization (IORC) process to convert the substituted cyclopentene into the tetracyclic skeleton of goniomitine with high chemo-, regio-, and diastereoselectivity.",10.1002/anie.201209970,2013-02-07,0.581720704226945
Synthesis,Iodoacetic Acid is an Efficient Reagent for the Synthesis of Amino Acid Derived 2-Aminobenzimidazoles,"Chiral, nonracemic, N-unprotected amino acids were converted into the corresponding N -benzimidazol-2-yl derivatives by a sequential procedure involving initial formation of isothiocyanates, their reaction with arene-1,2-diamines, and cyclization–desulfurization­ of the intermediate thioureas with iodoacetic acid. The simplified workup and the lack of volatile or toxic byproducts in the key desulfurization step renders iodoacetic acid a superior reagent to the usual reagent, iodomethane.",10.1055/s-0032-1316849,2013-02-06,0.5817095232118566
Organic Letters,Total Synthesis of (±)-Murrayazoline,The total synthesis of (+/-)-murrayazoline (1) is described. The characteristic hexa-heterocyclic structure of 1 was constructed by a combination of the intramolecular Friedel-Crafts-type Michael addition and Pd-catalyzed C-O coupling reactions. The N-substituted carbazole component was synthesized in one pot by the double N-arylation of a sterically hindered amine with a dibromobiphenyl derivative.,10.1021/ol800602v,2008-04-11,0.5817062330819723
Tetrahedron,Highly efficient synthesis of 5-benzyl-3-aminoindazoles,,10.1016/j.tetlet.2009.04.024,2009-04-13,0.5817033201595339
Journal of Organic Chemistry,Divergent Strategy for the Synthesis of α-Aryl-Substituted Fosmidomycin Analogues,"Fosmidomycin is the first representative of a new class of antimalarial drugs acting through inhibition of 1-deoxy-D-xylulose 5-phosphate (DOXP) reductoisomerase (DXR), an essential enzyme in the non-mevalonate pathway for the synthesis of isoprenoids. This work describes a divergent strategy for the synthesis of a series of alpha-aryl-substituted fosmidomycin analogues, featuring a palladium-catalyzed Stille coupling as the key step. An alpha-(4-cyanophenyl)fosmidomycin analogue emerged as the most potent analogue in the present series. Its antimalarial activity clearly surpasses that of the reference compound fosmidomycin.",10.1021/jo0700981,2007-04-12,0.5817000770730103
Synlett,"A Novel, One-Pot, Three-Component Synthesis of 5<i>H</i>-[1,3]Thiazolo[3,2-<i>a</i>]pyrimidine Derivatives","A novel synthesis of highly functionalized 5H-[1,3]thi­azolo[3,2-a]pyrimidines is described via a one-pot, three-component addition reaction between isocyanides, dialkyl acetylene-dicarboxylates and ethyl 2-oxo-2-(1,3-thiazol-2-ylamino)acetates in good yields.",10.1055/s-2007-991048,2007-09-25,0.581698911837136
Tetrahedron,"Structure and synthesis of alamaridine, a novel benzopyridoquinolizine alkaloid from",,10.1016/s0040-4039(00)84220-3,1986-01-01,0.5816949502006995
Tetrahedron,"Synthesis and structure elucidation of a novel ecdysteroid, gerardiasterone",,10.1016/s0040-4039(00)61409-0,1993-12-01,0.5816949502006995
Tetrahedron,Synthesis and structure of benzoboroxoles: novel organoboron heterocycles,,10.1016/s0040-4039(99)01303-9,1999-09-01,0.5816949502006995
Tetrahedron,"Synthesis and structure elucidation of novel 5-dinitromethyl-7-alkylamino-1,2,4-triazolo[4,3-a]-1,3,5-triazines",,10.1016/j.tetlet.2013.05.052,2013-05-20,0.5816949502006995
Tetrahedron,"Synthesis, structure and fluorescence of a novel diarylethene",,10.1016/j.tetlet.2004.11.162,2004-12-19,0.5816949502006995
Tetrahedron,What is the structure of barettin? Novel synthesis of unsaturated diketopiperazines.,,10.1016/s0040-4039(00)96483-9,1987-01-01,0.5816949502006995
Tetrahedron,"Structure and synthesis of reductiline, a novel metabolite from a variant of",,10.1016/s0040-4039(00)85765-2,1982-01-01,0.5816949502006995
Tetrahedron,"Synthesis and structure of novel alkylidenemalonaldehydes: 2-(diformylmethylene)-1,3-dithiane and -1,3-dithiolane as well as (2,3-diphenylcyclopropen-1-ylidene)malonaldehyde",,10.1016/s0040-4039(00)99429-2,1989-01-01,0.5816949502006995
Synthesis,"Total Synthesis of the Natural Carbazoles Glycozolicine, Mukoline, and Mukolidine, Starting from 4,5-Dimethyleneoxazolidin-2-ones","A novel and efficient synthesis of naturally occurring 1-methoxycarbazoles glycozolicine, mukolidine, and mukoline is developed by applying a regioselective Diels-Alder reaction of a 4,5-dimethyleneoxazolidin-2-one with acrolein. The cycloadduct is transformed to the corresponding functionalized diarylamine. The key palladium-catalyzed cyclization/deformylation cascade reaction of the latter leads to glycozolicine in high overall yield. Oxidation of the C6 methyl group provides the 6-formylcarbazole mukolidine, which is reduced to the respective natural alcohol mukoline.",10.1055/s-0030-1258444,2011-02-18,0.5816949264137291
Journal of Organic Chemistry,Application of Cp<sub>2</sub>TiCl-Promoted Radical-Induced Cyclization: An Expeditious Access to [<i>a</i>]-Annelated Indoles,"An efficient and novel route for assembling pyrrolo/piperido[1,2- a ]indoles is portrayed involving a radical-mediated reductive epoxide opening reaction of N -tethered epoxy-indoles that trigger facile intramolecular cyclization followed by an oxidative quenching step. Capitalizing on the operational simplicity of the method involving just two steps and use of an efficient C–C bond-forming reaction, this radical-based protocol enables the modular assembly of an important class of N -fused indole derivatives with versatile functional and structural diversity.",10.1021/acs.joc.0c00817,2020-05-29,0.5816830851001187
Journal of the American Chemical Society,Synthesis of Medium Ring Ethers. 5. The Synthesis of (+)-Laurencin,"The enantioselective synthesis of (+)-laurencin 1 has been achieved in 27 steps from ( R )-malic acid 20 . The key steps involved methylenation of the lactone 49 followed by intramolecular hydrosilation of the enol ether 14 (Scheme 11) and one carbon homologation of the diol 13 to give the key ethyl substituted cyclic ether 59 (Scheme 13). The lactone 49 was obtained by two efficient routes, namely a Claisen ring expansion (Scheme 3) followed by α-hydroxylation (Scheme 6) and a Yamaguchi lactonization (Scheme 11). Elaboration of the ( E )-pentenynyl side chain (Scheme 18) and introduction of bromine (Scheme 19) completed the synthesis of (+)-laurencin 1 .",10.1021/ja9709132,1997-08-01,0.5816826431935593
Tetrahedron,"Selenocyclisations of homoallylic sulfonamides: A highly stereoselective route to both cis- and trans-2,5-dihydropyrroles",,10.1016/s0040-4039(99)00380-9,1999-04-01,0.5816800690694645
Organic Letters,Accessing the Structural Diversity of Pyridone Alkaloids: Concise Total Synthesis of <i>Rac</i>-Citridone A,"A unique route to the structural diversity of pyridone alkaloids is described based on the concept of a common synthetic strategy. Three different core structure analogues corresponding to akanthomycin, septoriamycin A, and citridone A have been prepared by using a highly selective and novel carbocyclization reaction.",10.1021/ol2017802,2011-08-05,0.5816760040867224
Angewandte Chemie International Edition,Discovery of Inhibitors of the Wnt and Hedgehog Signaling Pathways through the Catalytic Enantioselective Synthesis of an Iridoid‐Inspired Compound Collection,Cousins you can count on: An iridoid-inspired compound collection was synthesized efficiently by the resolution of cyclic enones in an asymmetric cycloaddition with azomethine ylides. The collection contained novel potent inhibitors of the Wnt and Hedgehog signaling pathways.,10.1002/anie.201306948,2013-10-02,0.5816722109563945
Tetrahedron,A practical asymmetric synthesis of (R)-fluoxetine and its major metabolite (R)-norfluoxetine,,10.1016/s0040-4039(01)01877-9,2001-12-01,0.5816706555372058
Journal of Organic Chemistry,Indole Diterpene Synthetic Studies:  Development of a Second-Generation Synthetic Strategy for (+)-Nodulisporic Acids A and B,"A second-generation strategy for construction of (+)-nodulisporic acids A and B based on the development of a new, effective modular indole synthesis exploiting a sequential Stille cross-coupling/Buchwald-Hartwig union/cyclization tactic is disclosed. This strategy evolved due to the considerable acid instability of the C(24) hydroxyl group observed in several advanced intermediates during our first-generation approach.",10.1021/jo062423a,2007-05-19,0.5816701200961284
Organic Letters,"Transition-Metal-Free, Atom- and Step-Economic Synthesis of Aminoketopyrrolizines from Benzylamine, Acylethynylpyrroles, and Acylacetylenes","A concise, atom-economic strategy for the synthesis of pyrrolizines with amino and keto substituents has been developed. It includes the following key steps: (i) the base-catalyzed (K 3 PO 4 /DMSO) addition of a benzylamine to 2-acylethynylpyrroles and (ii) noncatalyzed addition of enaminones obtained to the triple bond of acylacetylenes followed by intramolecular cyclization of the intermediate pentadiendiones thus formed to the target 1-(benzylamino)-2-acyl-3-methylenoacylpyrrolizines.",10.1021/acs.orglett.7b00408,2017-03-21,0.5816666293590221
Synlett,The First and Efficient Synthesisof 7-Aryl-6-methoxycarbonylquinazolines via Unexpected Reactionof 6-Arylethynylpyrimidine-5-carbaldehydes and Methyl Mercaptoacetate,A highly concise synthesis of 7-aryl-6-methoxycarbonylquinazolines via reaction of 6-arylethynylpyrimidine-5-carbaldehydes and methyl mercaptoacetate is described.,10.1055/s-0028-1087514,2009-01-15,0.5816630464598751
Synthesis,The Atropo-Enantioselective Ring Opening of Achiral Lactone-Bridged Biaryls Using Chirally Modified Aluminum Hydrides,"All articles of this category The atropo-enantioselective preparation of the chiral biaryl 2-hydroxymethyl-1-(2-hydroxy-4, 6-dimethoxyphenyl)naphthalene (7) from 1,3-dimethoxy-6 H -benzo [ b ]naphtho[1,2- d ]pyran-6-one (3) is described, whereby two formal problems of stereoselective biaryl synthesis are independently solved: The carbon-carbon bond formation by the intramolecular aryl coupling of the ester-type prefixed aromatic halves, and the asymmetric induction at the pre-formed biaryl axis by the subsequent stereoselective ring-opening reaction, using chiral hydrogen nucleophiles.",10.1055/s-1992-26126,1992-01-01,0.5816630328982699
Organic Letters,Discovery of Annulating Reagents Enabling the One-Step and Highly Stereoselective Synthesis of Cyclopentyl and Cyclohexyl Cores,"The use of the unprecedented annulating reagents methyl N -( tert -butylsulfinyl)-4-chlorobutanimidate and methyl N -( tert -butylsulfinyl)-5-bromopentanimidate enables the diastereoselective preparation of 5- and 6-membered carbocycles bearing three contiguous stereocenters. These synthons undergo cycloaddition with a variety of Michael acceptors to form cyclopentane/cyclohexane rings with excellent stereochemical control, generating only one of the eight possible diastereomers. This novel methodology has enabled the highly enantioselective and high yielding synthesis of novel chemotypes of pharmacological relevance.",10.1021/acs.orglett.0c03695,2020-12-22,0.5816626690053441
Synthesis,An Efficient One-Pot Synthesis of Aminobenzimidazoles,An efficient one-pot procedure for the preparation of aminobenzimidazoles from dinitroaniline derivatives is described. The process helps to avoid the troublesome acetonitrile-mediated reductive ethylation reaction.,10.1055/s-2004-834925,2004-11-17,0.5816580918364733
European Journal of Organic Chemistry,Modified Fry Cyanation of a Chiral Pyridinium Salt: Asymmetric Syntheses of (–)‐Coniine and (–)‐Solenopsin A,Abstract The synthesis of chiral 2‐cyano‐Δ 4 ‐tetrahydropyridine 5 was carried out in 85 % yield through a modified two‐step Fry reductive cyanation of pyridinium salt (+)‐ 3c that used lithium triethylborohydride as the hydride donor. An alkylation–reduction sequence provided 2‐alkyl‐substituted tetrahydropyridines (+)‐ 10a and (+)‐ 10b in 72–75 % yield after chromatographic purification. This protocol has been applied to the asymmetric syntheses of piperidine alkaloids (–)‐coniine and (–)‐solenopsin A.,10.1002/ejoc.201300595,2013-07-12,0.5816466097720572
Journal of Organic Chemistry,Synthesis of Enantiomerically Pure Morphine Alkaloids:  The Hydrophenanthrene Route,"A concise, linear, total synthesis of (-)-dihydrocodeinone-a close synthetic precursor of (-)-codeine and (-)-morphine-has been achieved. The carbocyclic core of the alkaloid was provided in the form of a phenanthrenone, which was resolved by chromatography on cellulose triacetate. A cuprate conjugate addition was used to establish the crucial benzylic quaternary stereocenter and to introduce the C(2)-side chain. Dimeric byproducts provide evidence for a single electron transfer (SET) mechanism. Unusual S(N)2 and radical cyclizations were employed for the formation of the dihydrobenzofuran and the piperidine ring, respectively.",10.1021/jo9805394,1998-08-01,0.5816445594771156
Journal of the American Chemical Society,Total Synthesis of Bryostatin 2,"The total synthesis of the marine macrolide bryostatin 2 is described. The synthesis plan relies on aldol and directed reduction steps in order to construct the anti -1,3-diol array present in each of the principal subunits (A, B, and C). These fragments were coupled using a Julia olefination and subsequent sulfone alkylation. A series of functionalization reactions provided a bryopyran seco acid, which was macrolactonized under Yamaguchi conditions. Installation of the two enoate moieties took advantage of asymmetric phosphonate and aldol condensation strategies. Reduction of the C 20 ketone and simple protecting group operations then completed the synthesis of bryostatin 2. This flexible approach should provide access to a series of new analogues of this clinically important marine natural product.",10.1021/ja990860j,1999-08-01,0.5816439124166519
Journal of Organic Chemistry,Synthesis of the C(29)−C(45) Bis-pyran Subunit (E−F) of Spongistatin 1 (Altohyrtin A),"A synthesis of the C(29)-C(45) bis-pyran subunit 2 of spongistatin 1 (1a) is described. The synthesis proceeds in 19 steps from the chiral aldehyde ent-7, and features highly diastereoselective alpha-alkoxyallylation reactions using the gamma-alkoxy substituted allylstannanes 17 and 19, as well as a thermodynamically controlled intramolecular Michael addition to close the F-ring pyran. The E ring was assembled via the Mukaiyama aldol reaction of F-ring methyl ketone 3 and the 2,3-syn aldehyde 4.",10.1021/jo001236o,2000-11-21,0.5816374740085198
Synlett,"Synthesis of a Bicyclic Cation Related to Sterol Biosynthesis and Its Chemical Destiny, Part I","(opens in new window) Buy Article (opens in new window) Permissions and Reprints (opens in new window) All articles of this category (opens in new window) Synthesis of bicyclic tert -alcohol 1 has been accomplished by means of Hg(OTf) 2 -induced cyclization of tert -butyl bishomofarnesate as the key step. Bicyclic cation 2 , related to the sterol biosynthesis, is generated by the reaction of 1 with BF 3 . The chemical destiny of the cation 2 was traced and it confirmed the structure of three kinds of cyclization products to be 3 , 4 , and 5 . These tricyclic compounds are formed via trans-anti-trans 6/6/5 fused cation 6 . The tricyclic product 3 is the stereoisomer with Corey's enzymatic cyclization product of a 2,3-oxidosqualene type epoxide. Selective formation of the trans-anti-trans 6/6/5 fused cation 6 as the intermediate that corresponds to the biosynthetic intermediate of a dammarane-type triterpenoid is noteworthy. sterol biosynthesis - 6/6/5 fused tricyclic products - mercuric triflate - biomimetic olefin cyclization - migration of methyl group - stepwise mechanism",10.1055/s-1998-1576,1998-01-01,0.5816355001152486
Journal of the American Chemical Society,"All-Catalytic, Efficient, and Asymmetric Synthesis of α,ω-Diheterofunctional Reduced Polypropionates via “One-Pot” Zr-Catalyzed Asymmetric Carboalumination−Pd-Catalyzed Cross-Coupling Tandem Process","A highly efficient method for the synthesis of stereochemically pure (>/=99% ee and >50/1 dr) alpha,omega-diheterofunctional reduced polypropionates has been developed. The essential features of the method are represented by the conversion of inexpensive styrene into 2-methyl-4-phenyl-1-pentanol (1) in 50% yield over two steps from styrene via Zr-catalyzed asymmetric carboalumination (ZACA) reaction in the presence of (NMI)2ZrCl2 and Pd-catalyzed vinylation of the in situ generated isoalkylalanes in the presence of Zn(OTf)2 and a catalytic amount of Pd(DPEphos)Cl2. This ZACA-Pd-catalyzed vinylation may be repeated as needed without purification. After the final ZACA reaction, oxidation with O2 provides alpha-hydroxy-omega-phenyl reduced polypropionates, which can be fully or partially purified by chromatography. After acetylation, Ru-catalyzed oxidative cleavage of the Ph ring, and reduction with BH3.THF, the second chromatographic purification provides stereoisomerically pure alpha,omega-diheterofunctional reduced polypropionates (e.g., 9 and 11) that can be further converted to key intermediates 6 and 7 for the synthesis of ionomycin (4) and borrelidin (5), respectively, by known reactions.",10.1021/ja043534z,2005-02-11,0.581629499779453
Angewandte Chemie International Edition,Asymmetric Synthesis and Biological Properties of Uncialamycin and 26‐<i>epi</i>‐Uncialamycin,The highly potent DNA-cleaving molecule uncialamycin (1) was prepared in an asymmetric total synthesis featuring an enantioselective Noyori reduction. Compound 1 and its C26 epimer exhibit impressive broad-spectrum antibacterial properties and highly potent antitumor activities against a variety of cell lines.,10.1002/anie.200704577,2007-12-03,0.5816280996871356
Synthesis,"Convenient Laboratory Method for the Synthesis of Symmetrical 1,3-Diphenylacetone Derivatives","A practical one-pot, two-step procedure for the synthesis of symmetrical 1,3-diphenylacetone derivatives from the corresponding phenylacetate has been developed. This procedure has been demonstrated by the synthesis of 1,3-diphenylacetone at the >50-gram scale in >99% purity.",10.1055/s-0030-1260160,2011-08-08,0.5816280256649696
Organic Process Research & Development,"Pilot Plant Preparation of <i>tert-</i>Butyl-4-(2-hydroxyethyl)-4-(pyrrolidin-1-yl)-piperidine-1-carboxylate, An Intermediate of Novel Antiarteriosclerotics, Via a Safe, Scalable Reformatsky-Type Reaction","Reported here is a safe, scalable process via a Reformatsky-type reaction of iminium salt ( 4 ) followed by Red-Al reduction giving tert -butyl-4-(2-hydroxyethyl)-4-(pyrrolidin-1-yl)-piperidine-1-carboxylate ( 6 ), an intermediate of novel antiarteriosclerotics ( 1 ). The key points of this safe process are the use of trifluoroacetic acid (TFA) for the iminium salt formation, vigorous stirring for the Reformatsky reaction, and slow addition of methyl bromoacetate. Pilot manufacturing on the 500 L scale was achieved.",10.1021/op2001723,2011-08-01,0.5816209966968174
Organic Letters,Total Synthesis of (±)-<i>O</i>-Methyl PD 116740,[reaction: see text] Condensation of the phthalide sulfide with an ortho-quinone monoketal was employed as a key step in the first total synthesis of a derivative of (+/-)-PD 116740.,10.1021/ol026104r,2002-06-01,0.5816189386178304
Synthesis,First Total Syntheses of (±)-Callyspongidic Acids and 2-epi-(±)-Callyspongidic Acids,"Abstract The first total syntheses of (±)-callyspongidic acids and 2-epi-(±)-callyspongidic acids were achieved in high overall yield from epoxy ester derived from commercially available l-(+)-tartaric acid. The key features of these syntheses are the stereoselective opening of epoxide with organocuprates and the chemoselective addition of Grignard reagent to ketone in the presence of ester. The synthetic route reported here is operationally simple, very short and amenable for the synthesis of several analogues of this class.",10.1055/s-0041-1737805,2022-02-01,0.5816186207896716
Tetrahedron,Asymmetric routes towards polyfunctionalized pyrrolidines: Synthesis and reactivity of a chiral silyloxypyrrole,,10.1016/0040-4039(95)02388-7,1996-02-01,0.5816182987414016
European Journal of Organic Chemistry,Electrogenerated Chiral 4-Methoxy-2-oxazolidinones as Diastereoselective Amidoalkylation Reagents for the Synthesis of β-Amino Alcohol Precursors,"A flexible and efficient synthesis of enantiomerically pure 4,5-substituted 2-oxazolidinones − important target molecules as precursors of pharmacologically active 2-oxazolidinones, β-amino alcohols, β-blockers and azasugar derivatives − is described. As starting materials, the enantiopure storage forms of chiral N-acyliminium ions (4RS,5S)-5-chloromethyl-4-methoxy-1,3-oxazolidin-2-one (2) and (4RS,5R)-4-methoxy-5-methyl-1,3-oxazolidin-2-one (3) were used; these are readily available from the chiral pool with the aid of electrochemical transformations. Substitution of the 4-methoxy group in building blocks 2 and 3 with a large variety of organometallic nucleophiles resulted in the trans-diastereoselective formation of enantiopure 4,5-disubstituted 2-oxazolidinones, with a high degree of flexibility in the substituent at the 4-position.",10.1002/1099-0690(200107)2001:13<2425::aid-ejoc2425>3.0.co;2-2,2001-07-01,0.5816157665881172
Tetrahedron,Pyrophosphate tetraester intermediate of coupling reactions in the phosphotriester approach to the synthesis of deoxyoligoribonucleotides,,10.1016/s0040-4039(00)85864-5,1982-01-01,0.5816157379042552
Tetrahedron,Pyrophosphate tetraester intermediate of coupling reactions in the phosphotriester approach to the synthesis of deoxyligoribonucleotides,,10.1016/0040-4039(82)80153-6,1982-01-01,0.5816157379042552
Chemical Science,Pd-catalyzed stereoselective tandem ring-opening amination/cyclization of vinyl γ-lactones: access to caprolactam diversity,")-configured ε-amino acid can be cyclized using a suitable dehydrating agent in an efficient one-pot, two-step sequence. This overall highly chemo-, stereo- and regio-selective transformation streamlines the production of a wide variety of modifiable and valuable caprolactam building blocks in an operationally attractive way.",10.1039/d0sc03647a,2020-01-01,0.581607979860228
Synthesis,"Synthesis of Echinotinctone, A Fungal Fluorone Pigment","All articles of this category Echinotinctone ( 3 ) is formed by acid-catalyzed condensation of 1,2,4-trihydroxytoluene ( 1 ) with orcylaldehyde ( 2 ), a reaction mimicking the probable biosynthesis. A more efficient stepwise synthesis proceeds via the benzophenone intermediate 11 , which can be converted to 2,6-dihydroxy-1,8-dimethyl-3 H -xanthen-3-one ( 3 ) by LiAlH 4 reduction and subsequent acid-catalyzed ring closure. natural products - basidiomycetes - quinone methides - xanthenes - fluorones - phenols - cyclizations - benzylations",10.1055/s-2000-6398,2000-01-01,0.5816058588769307
Synlett,"Stereoselective Synthesis of Orthogonally Protected β-Hydroxy-α-,γ-diamino Butyric Acids","A synthesis of all four stereoisomers of the unnatural amino acid β-OH Dab (α,γ-diamino butyric acid) in orthogonally protected form is described. The synthetic strategy relies on a three-step sequence comprising stereoselective dihydroxylation, sulfite formation, and regioselective sulfite opening with azide to build the densely functionalized carbon skeleton.",10.1055/s-0030-1260331,2011-09-27,0.5816027412532186
European Journal of Organic Chemistry,"Total Synthesis of Unsymmetrical Benzils, Scandione and Calophione A","Abstract The synthesis of the title unsymmetrical benzils, scandione and calophione A, is described. The key processes involve intramolecular cyclization reaction of the carbanion at the benzylic position of the arylbenzyl ether to the adjacent ester group followed by oxidation. The palladium(II)‐catalyzed oxidative cyclization was also used to establish the benzofuran unit of calophione A.",10.1002/ejoc.201301722,2014-02-20,0.5816024040912302
Synlett,Synthesis of Isocryptolepinevia a Pd-Catalyzed ‘Amination-Arylation’ Approach,Isocryptolepine (cryptosanguinolentine) has been synthesized in three steps via a new approach starting from commercially available 4-chloroquinoline and 2-chloroaniline. The new methodology consists of two consecutive palladium-catalyzed reactions; a selective Buchwald-Hartwig amination followed by an intramolecular arylation reaction.,10.1055/s-2003-38364,2003-01-01,0.5815977801725436
Synthesis,A Novel Synthesis of Acyclic<i>N</i>-(α-Hydroxybenzyl)benzamides,All articles of this category N -Hydroxybenzamides 1 react with hydroxymethylbenzotriazole ( 2 ) to give (benzotriazol-1-yl)methyl derivatives 3 . These are converted by aryl Grignard reagents into acyclic N -(α-hydroxybenzyl)-benzamides 6 .,10.1055/s-1990-26974,1990-01-01,0.5815976263203444
Tetrahedron,Asymmetric synthesis V. Enantiospecific synthesis of β-aminoalcohols in the piperidine series : (+)-β-conhydrine,,10.1016/s0040-4039(00)89255-2,1985-01-01,0.5815951095661798
Synthesis,"Enantioconservative Synthesis of Polysubstituted Pyrimido[4,5-b]azepines","A three-step enantioconservative protocol was developed for the synthesis of polysubstituted pyrimido[4,5-b]azepines. First, 1,3-dimethyl-6-[N-(2-alkoxycarbonylalkyl)amino]uracils were synthesized by nucleophilic substitution of 6-chloro-1,3-di­methyluracil with amino acids. Subsequent acylation of the uracils by a mixture of acetic anhydride and cyanoacetic acid gave the corresponding 5-cyanoacetylated pyrimidines. In the final step, the pyrimidines were subjected to Dieckmann cyclization with a sodium alcoholate in the corresponding alcohol to afford the corresponding pyrimido[4,5-b]azepines. By using uracils of N-monosubstituted amino acids, cyclization was combined with ring opening of the pyrimidine ring system to afford polysubstituted azepines.",10.1055/s-0029-1218758,2010-04-28,0.5815915078258878
Tetrahedron,New cleavable isocyanides for the combinatorial synthesis of α-amino acid analogue tetrazoles,,10.1016/j.tetlet.2005.08.101,2005-09-10,0.5815867851390659
European Journal of Organic Chemistry,Asymmetric Synthesis of the C1–C13 Fragment of the Marine Metabolite Bistramide K,"Abstract A synthetic study on the construction of the C1–C13 fragment of bistramide K is described. This unit differs from other members of the bistramide family, which are equipped with a pyran structure at C6–C11. In bistramide K, the linear C1–C13 portion contains three stereogenic centers as well as two supplementary ( E )‐olefin positions. The key step in the synthesis was the elaboration of the ( E )‐olefin C6–C7 by using a Julia–Kocienski reaction between aldehyde 4 and benzothiazolesulfone 15 .",10.1002/ejoc.201000881,2010-09-22,0.5815865094227549
Organic Letters,Bioinspired Total Synthesis of (±)-Chaetophenol C Enabled by a Pd-Catalyzed Cascade Cyclization,A novel Pd(II)-catalyzed cascade reaction has been developed that consists of a highly regio- and stereoselective oxa [4 + 2] cycloaddition reaction of o-alkynylbenzaldehydes and an intramolecular carboxylic group quenching of the in situ generated oxonium ion. This new reaction provides a one-step construction of the tetracyclic core structure of chaetophenol C from two simple starting materials. The developed chemistry was successfully applied to the first total synthesis of chaetophenol C and dozens of its analogues.,10.1021/acs.orglett.7b02124,2017-08-07,0.5815795830071849
Synthesis,"An Improved Method for the Synthesis of 2-Thioxo-2,3-dihydro-1,3-benzoxazoles [2(3<i>H</i>)-Benzoxazolethiones]",,10.1055/s-1983-30580,1983-01-01,0.5815694795795567
Synthesis,Indium-Mediated Allylation Reaction in Aqueous Media: Synthetic Studies Towards the Total Synthesis of Dysiherbaine,A stereospecific route to the key intermediate 4 for the total synthesis of dysiherbaine has been successfully developed based on the indium-mediated allylation reaction in aqueous media. Further manipulation to the advanced intermediate 28 has resulted in the discovery of a series of highly stereoselective processes.,10.1055/s-2003-38058,2003-01-01,0.5815652176082264
Tetrahedron,Stereoselective synthesis of 25-hydroxyvitamin D2 side chain via the acetal template route,,10.1016/s0040-4039(00)96572-9,1987-01-01,0.5815625632089831
Synlett,Synthesis of Novel 1-Aryl-9H-xanthen-9-ones,"A novel route for the synthesis of 1-aryl-9H-xanthen-9-ones is reported. This methodology involves the condensation of 2-methylchromone with cinnamaldehydes leading to (E, E)-2-(4-arylbuta-1,3-dien-1-yl)-4Hchromen-4-ones. The final steps involved electrocyclization and oxidation of the latter compounds, in an one-pot synthesis, giving the desired 1-aryl-9H-xanthen-9-ones.",10.1055/s-0030-1260567,2011-05-16,0.5815588362097569
Organic Letters,First Asymmetric Synthesis of the Cyclohexanone Subunit of Baconipyrones A and B. Revision of Its Structure,"[reaction: see text] An asymmetric synthesis of the 3,5-dihydroxycyclohexanone subunit of baconipyrones A and B, as well as that of the hydroxydiketone subunit of baconipyrones C and D ((-)-(4S,6S)-4,6-dimethyl-5-hydroxynonan-3,7-dione), is described. Key steps include sulfur dioxide-induced additions of enoxysilanes to 1,3-dioxy-1,3-dienes, followed by retro-ene desulfitations (retro-ene elimination of SO(2)).",10.1021/ol048988f,2004-08-06,0.5815565473860935
Tetrahedron,Synthesis of polycyclic pyrazoles through formation of the first fused heterocyclic o-quinodimethane intermediate,,10.1016/j.tetlet.2005.05.079,2005-06-10,0.5815554697401079
European Journal of Organic Chemistry,Enantioselective Syntheses of (–)‐Alloyohimbane and (–)‐Yohimbane by an Efficient Enzymatic Desymmetrization Process,"Enantioselective syntheses of (–)‐alloyohimbane and (–)‐yohimbane were accomplished in a convergent manner. The key step involves a modified mild protocol for the enantioselective enzymatic desymmetrization of a meso ‐diacetate. This provides convenient access to an optically active monoacetate in multi‐gram quantities and in high enantiomeric purity. This monoacetate was converted to (–)‐alloyohimbane. Reductive amination of the derived aldehyde caused isomerization to the trans ‐product and, ultimately, the formation of (–)‐yohimbane.",10.1002/ejoc.201601171,2016-11-28,0.5815553215779703
Chemical Science,CO-to-sugars conversion from one-pot two-step electro-organocatalytic process,A one-pot two-step process combining electroreduction and organocatalysis to selectively transform CO into C 5–6 carbohydrates with formaldehyde as the key intermediate.,10.1039/d5sc06667k,2025-01-01,0.5815521682284158
Organic Process Research & Development,Development of a Commercially Viable Clonazepam Process,"A commercial process to clonazepam ( 1 ) is described. An advanced chloro intermediate, 2-(2-chloroacetamido)-5-nitro-2‘-chlorobenzophenone ( 6 ), is activated to the corresponding iodide 2-(2-iodoacetamido)-5-nitro-2‘-chlorobenzophenone ( 7 ) via substitution with potassium iodide. Subsequent alkylation of ammonia with 7 yields the open form of clonazepam ( 8 ). The intermediate 8 is isolated as the hydrochloride salt 8b, cyclized to 1, and purified to yield United States Pharmacopoeia specification material. Formation of the known impurity 3-amino-4-(2-chlorophenyl)-6-nitro-2(1 H )-quinolinone ( 9 ), as well as of the newly identified dimeric impurity N -[2-(2-chlorobenzoyl)-4-nitrophenyl]-2-{[[[2-(2-chlorobenzoyl)-4-nitrophenyl]carbamoyl]methyl]amino}acetamide ( 10 ), is minimized. The robust purification scheme readily removes both organic and inorganic impurities. This synergistic combination of pieces of several patented routes results in a process that is more viable than any previously described process.",10.1021/op9702152,1997-07-01,0.5815473480712119
Journal of Organic Chemistry,Total Synthesis of the Bridged Indole Alkaloid Apparicine,"An indole-templated ring-closing metathesis or a 2-indolylacyl radical cyclization constitute the central steps of two alternative approaches developed to assemble the tricyclic ABC substructure of the indole alkaloid apparicine. From this key intermediate, an intramolecular vinyl halide Heck reaction accomplished the closure of the strained 1-azabicyclo[4.2.2]decane framework of the alkaloid with concomitant incorporation of the exocyclic alkylidene substituents.",10.1021/jo901986v,2009-10-14,0.5815450946624998
Organic Letters,Total Synthesis of <i>ent</i>-Callilongisin B,"The first enantioselective total synthesis of tricyclic diterpenoid callilongisin B, which was isolated from Callicarpa longissima, has been achieved. The synthetic method includes a diastereoselective 1,4-addition and Hosomi–Sakurai allylation followed by Wacker oxidation, intramolecular aldol reaction to construct a six-membered ring, and oxidative dearomatization accompanied by diastereoselective δ-lactonization.",10.1021/acs.orglett.1c02473,2021-08-23,0.5815422419297851
Journal of Organic Chemistry,"Total Synthesis of Naturally Occurring <i>Amaryllidaceae</i> Alkaloids, (−)-Elwesine and (−)-<i>epi</i>-Crinine","Catalytic asymmetric total synthesis of the naturally occurring Amaryllidaceae alkaloids, (−)-elwesine ( 2 ), (−)-dihydrooxocrinine ( 5 ), and (−)- epi -crinine ( 3 ) bearing the characteristic 5,10 b -ethanophenanthridine framework has been reported. The synthesis features a key CBS reduction to generate an enantioenriched allylic alcohol (97% ee), followed by an orthoester Johnson–Claisen [3,3]-sigmatropic rearrangement to construct a sterically demanding all-carbon quaternary center at the pseudobenzylic position. Subsequent allylic oxidation furnishes the corresponding enone intermediate 7 . Furthermore, a strategic sequence comprising ester aminolysis, aza -Michael addition, and a Pictet–Spengler cyclization efficiently constructed the 5,10 b -ethanophenanthridine scaffold of these Amaryllidaceae alkaloids.",10.1021/acs.joc.5c01480,2025-08-26,0.5815405065567728
Synthesis,A Formal Synthesis of (±)-Cephalotaxine via Pauson-Khand Reaction,A concise route toward the formal synthesis of (±)-cephalotaxine has been developed. An intermolecular Pauson–Khand reaction was adopted to construct the cyclopentenone ring efficiently with high regioselectivity.,10.1055/s-0032-1318116,2013-01-31,0.5815376849120765
European Journal of Organic Chemistry,Total Synthesis and Structure Confirmation of Cryptocaryol A,"Abstract The first enantioselective total synthesis of Pdcd4‐stabilizing cryptocaryol A, a secondary metabolite obtained from a tropical tree, has been achieved through an iterative approach to the 1,3‐polyol motif. The key steps are a Maruoka allylation, a Reetz chelation‐controlled allylation with 1,3‐induction, iterative diastereoselective iodocyclization, and ring‐closing metathesis reactions.",10.1002/ejoc.201201309,2012-12-19,0.5815368409701898
Journal of Organic Chemistry,"First Synthesis of <i>N</i>-(3-Carboxylpropyl)-5-amino-2-hydroxy-3- tridecyl-1,4-benzoquinone, an Unusual Quinone Isolated from <i>Embelia </i><i>ribes</i>","The first synthesis of the unusual nitrogen-containing 3-alkyl-1,4-benzoquinone, N-(3-carboxylpropyl)-5-amino-2-hydroxy-3-tridecyl-1,4-benzoquinone, isolated from Embelia ribes, is reported. The key steps are a microwave-assisted combined Mitsunobu reaction-Claisen rearrangement to introduce the alkyl side chain into 2,5-dimethoxyphenol, followed by alkene reduction, oxidation to the quinone, and sequential displacement of the methoxy groups with hydroxide and GABA tert-butyl ester. Two other naturally occurring benzoquinones, O-methylrapanone and rapanone, were also prepared en route.",10.1021/jo702101w,2007-11-14,0.5815330847158492
Tetrahedron,Synthesis of novel chiral monophosphine ligands derived from isomannide and isosorbide. Application to enantioselective hydrogenation of olefins,,10.1016/j.tetlet.2012.07.035,2012-07-15,0.5815274707418348
Synthesis,"Synthesis of New 4-Nitrosophenyl-1,4-dihydropyridines of Pharmacological Interest","The synthesis and characterization of a series of 4-nitro­sophenyl-1,4-dihydropyridines derived from the respective nitro compounds of pharmacological interest is described. The complete synthetic pathway is based on the classical Hantzsch 1,4-dihydropyridine synthesis to obtain the nitrophenyl 1,4-dihydropyridines in a first step, followed by chemical reduction of the nitro compound to the corresponding hydroxylamine and further oxidation to the nitroso derivative. The synthesis and characterization of the compounds is described.",10.1055/s-2003-42453,2003-01-01,0.5815273714130142
Green Chemistry,One-pot hydrodeoxygenation of bioderived furans into octane at low temperatures <i>via</i> an octanediol route,A novel octanediol-route was developed to produce octane from bioderived furans at low temperatures.,10.1039/d1gc00916h,2021-01-01,0.5815255642981151
Synlett,Stereoselective Synthesis of the Epoxysuccinyl Peptide E-64c,A highly diastereoselective PTC epoxidation is employed in the synthesis of the potent cysteine protease inhibitor E-64c.,10.1055/s-2006-948191,2006-08-01,0.5815226941777034
Journal of Organic Chemistry,Synthesis of the Sponge-Derived Plakortone Series of Bioactive Compounds,"The Caribbean sponges of the genus Plakortis, P. halichondrioides, and P. simplex have provided a series of biologically active furanolactones-the plakortones A-D (1-4) from the former sponge and B-F (2-6) from the latter. The defining motif of the plakortones is a sterically congested 2,6-dioxabicyclo[3.3.0]octan-3-one moiety, the emblematic furanolactone core. This core is efficiently accessed by a palladium(II) mediated hydroxycyclization-carbonylation-lactonization cascade with an appropriate ene-1,3-diol. Total syntheses of plakortones C (3) and F (6) are now described which settle constitutional and stereochemical features in this group of secondary metabolites. Acquisition of plakortone D (4), the most effective activator of SR-Ca(2+)-pumping ATPase, utilized stereodefined lactone cores that resulted from asymmetric dihydroxylation of protected homoallylic alcohol 29. A derived lactone aldehyde was then coupled with an independently generated, sulfone-activated side chain unit, 57. The 11,12-E-double bond, carried through the sequence as a protected, stereodefined diol, was released therefrom by stereospecific syn-elimination via an orthoester derivative. In this way, plakortone D (4) was demonstrated to possess the (3S,4S,6S,10R,11E) configuration. Racemic plakortone E (5) was also acquired by using the Pd(II) induced sequence, but in this case, the required, complete acyclic system 52 was assembled first. Plakortone C (3) resulted from a sequence commencing with (R)-(+)-3-hydroxy-2-methylpropionate, with a derived iodide 76 alkylating the enolate of the butyramide 77 generated from (1S,2S)-(+)-pseudoephedrine. The liberated primary alcohol 79 was converted by standard procedures to key enediol 89 which, with the Pd(II) protocol, afforded the major separable plakortones 90 and 91, with the former being identical with natural plakortone C (3). Very mild hydrogenation of 90 afforded a saturated plakortone, identical with natural plakortone F (6), thus establishing its structure and absolute stereochemistry. Available information on the stereoselective routes to plakortones E (5) and B (2) are also outlined, so that the constitution and absolute stereochemistry of plakortones B-F are now established.",10.1021/jo101224w,2010-09-02,0.5815226513670667
Journal of Organic Chemistry,Enantioselective Total Synthesis of (−)-Curcuquinone via Regioselective Chromium-Mediated Benzannulation,"[reaction: see text] A short and efficient, high-yielding enantioselective total synthesis of the marine natural product (-)-curcuquinone 1 is reported involving a regioselective [3 + 2 + 1]-benzannulation reaction as the key step. Additionally, this strategy allows the isolation of curcuhydroquinone monomethyl ether 9 as an intermediate of the benzannulation reaction and its subsequent further protection toward diversified hydroquinones.",10.1021/jo0500939,2005-04-01,0.5815162306819134
Journal of Organic Chemistry,Bischler−Napieralski Cyclization−<i>N</i>/<i>C</i>-Alkylation Sequences for the Construction of Isoquinoline Alkaloids. Synthesis of Protoberberines and Benzo[<i>c</i>]phenanthridines <i>via</i> C-2‘-Functionalized 3-Arylisoquinolines<sup>1</sup>,"Efficient synthetic routes to isoquinoline alkaloids of the protoberberine and benzo[c]phenanthridine classes are reported. The key transformations are derived from the intramolecular cyclization of C-2'-functionalized N-(1,2-diarylethyl)amides or enamides via 3-arylisoquinoline derivatives. Thus, under Bischler-Napieralski reaction conditions (PCl(5), nitrile as solvent, room temperature) N-(1,2-diarylethyl)amides 12 regioselectively yielded 2,3-disubstituted 13,14-dihydroprotoberberinium salts 20, a scarcely studied oxidation state in this class of alkaloids. Subsequent reduction of the iminium bond gave the known coralydine (21a) and O-methylcorytenchirine (21b) and their 8-phenyl analogue 21c. The one-pot preparation of these dihydroprotoberberinium salts 20 is shown to proceed with cleavage of the silyl ether and immediate halogenation of the resulting hydroxyl group, followed by cyclization of the obtained N-(1,2-diarylethyl)amide 18 to a 3,4-dihydroisoquinoline derivative 19 and subsequent intramolecular in situ N-alkylation of the latter imine. Ready access to planar 8,9-dialkoxylated benzo[c]phenanthridinium salts is also described. Condensation of ketoester 23 with benzylamine in the presence of titanium(IV) chloride, followed by acetylation, afforded a mixture of naphthylamide 24 and (E)-enamide 25. Both enamides were efficiently cyclized by POCl(3). While the planar benzo[c]phenanthridinium salt 26 was directly produced from 24, the (E)-enamide 25 gave the 3-arylisoquinolinium salt 27, which was reduced and intramolecularly C-alkylated to yield the tetracyclic nucleus of these alkaloids.",10.1021/jo960007s,1996-01-01,0.5815140736294353
Synlett,"Stereocontrolled Synthesis of a Trihydroxylated Pyrrolizidine Alkaloid, 7-Deoxyalexine","All articles of this category An enantiomerically and diastereomerically pure route has been developed for the asymmetric synthesis of (1 R ,2 R ,3 R ,7 aS )-trihydroxylated pyrrolizidine alkaloid, 7-deoxyalexine, featuring the stereocontrolled elaboration of the functionalized homochiral lactam derived from 2,3,5-tri- O -benzyl-β-d-arabinofuranose. alexine - pyrrolizidine alkaloid - chiral lactam - nucleophilic addition - arabinofuranose",10.1055/s-2000-6677,2000-01-01,0.5814969212662092
Synthesis,Practical Syntheses of N-Acetyl (E)-β-Arylenamides,A facile and practical method for the preparation of ( E )-β-arylenamides [( E )- N -(1-arylprop-1-en-2-yl]acetamides] has been developed by reductive acetylation of the corresponding oximes with iron(II) acetate as the reducing reagent. Employment of hexamethylphosphoramide as the solvent was found to be critical for the high E / Z selectivity. The methodology has been applied in efficient syntheses of a key chiral intermediate of tamsulosin by asymmetric hydrogenation.,10.1055/s-0033-1339976,2013-10-14,0.5814958190576136
Tetrahedron,A new approach to the efficient indole synthesis by allene intramolecular cycloaddition,,10.1016/s0040-4039(00)84389-0,1986-01-01,0.5814900916789378
Synlett,"New, Simple and Versatile Synthesis of Protected α-Alkylidene-β-amino Acids from Activated Vinylphosphonates",A two-step route to Boc-protected α-alkylidene-β-amino esters was developed by addition of sodium tert-butylcarbamate to ethyl 2-diethoxyphosphoryl-2-alkenoates followed by the Horner-Wadsworth-Emmons olefination of aldehydes using intermediate 2-diethoxyphosphoryl-3-tert-butoxycarbonylaminoalkanoates.,10.1055/s-2006-944184,2006-06-01,0.5814891525357764
Synthesis,"Synthesis and Optical Resolution of 3,3,3′,3′-Tetramethyl-1,1′-spirobiindane-7,7′-diol","A novel chiral C2-symmetric spiro diol, 3,3,3′,3′-tetramethyl-1,1′-spirobiindane-7,7′-diol (TMSIOL), was conveniently prepared via practical seven-step route from Bisphenol A in 45.1% overall yield. l-Menthyl chloroformate is used as optical resolving agent for the separation of the two enantiomers of TMSIOL.",10.1055/s-0037-1610831,2018-09-04,0.5814874930551307
Tetrahedron,The first synthesis of the ABCD ring system of manzamine A. Construction of the macrocyclic ring D,,10.1016/s0040-4039(00)76864-x,1994-05-01,0.5814839212135657
Tetrahedron,Novel and convenient route to substituted succinates. The dimerization of ketene silyl acetals promoted by titanium tetrachloride,,10.1016/s0040-4039(01)83666-2,1977-01-01,0.5814809739722675
Organic Letters,Highly Enantioselective and Organocatalytic α-Amination of 2-Oxindoles,An effective method for the asymmetric synthesis of 3-amino-2-oxindoles was developed. The tetrasubstituted chiral carbon center was generated by asymmetric amination of N-unprotected 2-oxindoles with azodicarboxylate catalyzed by commercial biscinchona alkaloids in good to excellent yields with high enantioselectivities.,10.1021/ol901405r,2009-08-05,0.581479199307602
Journal of Organic Chemistry,Total Synthesis of Notoryne,"The structure of notoryne comprises a halogenated 2,2'-bifuranyl moiety along with a terminal cis-enyne unit. In this work, we document the first total synthesis of notoryne, confirming its assigned relative and absolute configurations. The devised route comprises a glucose diacetonide-derived chiral pool intermediate as the starting point and 5- endo bromo-etherification for making the key bis-furan unit, anomeric C-allylation, as well as a relay cross-metathesis to install the cis-enyne unit.",10.1021/acs.joc.8b01757,2018-09-14,0.581479083853227
Synlett,A Stereoselective Route to trans-1-Arylthio-2-aminoindanes,All articles of this category The acid catalysed ring opening of the 2-ethoxy oxazoline 1 with aryl thiols provides a convenient route to the trans -1-arylthio-2-aminoindane derivatives 4a-e . oxazoline - thiol - indane,10.1055/s-1996-5454,1996-05-01,0.5814711763389
Synlett,"Asymmetric Synthesis of 6,6’-Dialkyl and -Diphenyl-2,2’-Biphenyldiols by Using Menthone as a Chiral Template","All articles of this category A general method for the preparation of axially chiral ( S )-6,6’-dialkyl- and -diphenyl-2,2’-biphenyldiols are developed. Enantiomerically pure acetal 1 , prepared by the stereoselective reaction of 2,2’,6,6’-biphenyltetrol with l -menthone, is converted into bis(triflate) ( S )- 4 in three steps. Palladium(0)-catalyzed coupling reaction of ( S )- 4 with organoboron reagents and deprotection of the coupling products afford biphenyldiols ( S )- 8 of high optical purities. asymmetric synthesis - axial chirality - 2,2’-biphenyldiols - palladium(0)-catalyzed cross coupling reaction - organoboron reagents",10.1055/s-1995-4938,1995-03-01,0.5814679832255081
Angewandte Chemie International Edition,"A New, Simple Route to Novel Gold Clusters: Structure of an Au6Ag Wheel with a Gold Rim","A precious metal cartwheel is one way to describe the novel heteronuclear compound [Au6Ag(μ-C6H2iPr3)6]CF3SO3 (see picture, isopropyl groups are omitted) which displays an unusual planar hexacoordination for the silver(I) center. A convenient and simple synthesis of new gold heterometallic clusters is presented.",10.1002/1521-3773(20000703)39:13<2353::aid-anie2353>3.0.co;2-r,2000-07-03,0.5814626855656574
Organic Letters,"Enantioselective and Regiodivergent Gold and Chiral Brønsted Acid Catalyzed Cycloisomerization/Diels–Alder Reaction of 1,10-Dien-4-yn-3-yl Acetates: Synthesis of Norbornene-Embedded Tricarbocycles","A synthetic method for the enantioselective and regiodivergent synthesis of hexahydro-2 H -2,4a-methanonaphthalen-4-yl and octahydro-2,4-methanoazulen-1-yl esters that relies on the gold(I)- and chiral Brønsted acid-catalyzed cycloisomerization/Diels–Alder (CDA) reaction of ( E )-1,10-dien-4-yn-3-yl acetates is described.",10.1021/acs.orglett.4c00621,2024-04-01,0.5814618592961436
Angewandte Chemie International Edition,Concise and Stereodivergent Approach to Chromanone Lactones through Copper‐Catalyzed Asymmetric Vinylogous Addition of Siloxyfurans to 2‐Ester‐Substituted Chromones,"Vicinal oxygen-containing tetra- and tri-substituted stereocenters exist widely in chromanone lactone and tetrahydroxanthone natural products. Their enantioselective construction in a single step remains elusive and poses a formidable challenge for chemical synthesis. Here, we report the first copper(I)-catalyzed asymmetric vinylogous additions of siloxyfurans to 2-ester-substituted chromones, which enable concise and enantioselective assembly of chromanone lactones. Both syn and anti adducts can be accessed with excellent diastereo- and enantioselectivity by judicious choice of the chiral ligands. Our approach allowed for the efficient synthesis of (-)-blennolide B with precise stereochemical control, which provides a formal synthesis of secalonic acid A.",10.1002/anie.202203128,2022-04-27,0.5814559335426739
Organic Letters,Passerini Reaction−Amine Deprotection−Acyl Migration Peptide Assembly: Efficient Formal Synthesis of Cyclotheonamide C,"A short, convergent, formal total synthesis of cyclotheonamide C is described. The key linear pentapeptide intermediate is assembled at the same time as the elaboration of the alpha-hydroxyhomoarginine (H-hArg) residue via a three-component Passerini reaction-amine deprotection-O,N-acyl migration strategy.",10.1021/ol900048r,2009-02-09,0.5814512235039052
Organic Letters,Asymmetric Synthesis of Ramariolides A and C through Bimetallic Cascade Cyclization and <i>Z</i>–<i>E</i> Isomerization Reaction,"A short and flexible asymmetric synthesis of ramariolides A and C was accomplished. A bimetallic catalytic system consisting of Pd-Cu-mediated cascade cyclization, unprecedented Z-E isomerization by a Ru-based metathesis catalyst, and late-stage stereoselective epoxidation are the key steps involved in the synthesis.",10.1021/acs.orglett.7b00202,2017-02-16,0.5814495288761592
Synlett,The Synthesis of a Novel <i>C</i>-Nucleoside Designed as Guanosine Analogue,"The syntheses of a novel C-nucleoside which can be viewed as 8-aza-3,9-dideazaguanosine, as well as of the corresponding heterocyclic base, are described. N-[4-(2,3,5-tri-O-Acetyl-β-d-ribofuranosylmethyl)-2-methoxypyridin-3-yl]acetamide was regiospecifically nitrated and upon reduction and protection of the amino group underwent ring closure to the corresponding pyrazolopyridine derivative. The guanosine analogue was obtained via successive cleavage of the protecting groups.",10.1055/s-0028-1087276,2008-11-27,0.5814488927086024
Organic Letters,Diastereoselective Synthesis of <i>N</i>-Glycosides via Buchwald–Hartwig Coupling,"Herein we report a practical and highly efficient methodology for the β-selective synthesis of N -glycosides via Buchwald–Hartwig coupling. This glycosylation strategy employs glycosyl chloride with different amine aglycones and is catalyzed by an inexpensive copper(I) catalyst under mild, ligand-free conditions. The synthetic applicability is further demonstrated through the gram-scale reaction and the late-stage functionalization of bioactive molecules. Mechanistic insights and the critical role of the glycosyl iodide intermediate in the catalytic cycle are highlighted.",10.1021/acs.orglett.5c03334,2025-08-28,0.5814478613466983
Tetrahedron,A new synthesis of spirovetivanes via the spiro-acylion intermediate,,10.1016/s0040-4039(01)85911-6,1979-01-01,0.5814457426537513
Journal of Organic Chemistry,"Unexpected Single-Step Formation of 1,2-<i>a</i><i>nti</i>-Heterodisubstituted Calix[4]arenes upon Alkylation of a Tribenzoyl Precursor","The selective preparation and complete structural characterization of a small series of 1,2-anti-heterodisubstituted calix[4]arenes has been accomplished. These compounds were obtained in two steps from unsubstituted p-tert-butylcalix[4]arene by tribenzoylation and a subsequent one-pot, two-step sequence involving alkylation with simultaneous partial deacylation, resulting in heterodisubstituted calixarenes carrying an alkyl and an aroyl group. The monoalkyl-tribenzoyl intermediate, prior to in situ deprotection, could also be isolated.",10.1021/jo035150h,2003-10-01,0.5814408364063615
Journal of Organic Chemistry,A New Class of Glycosidase Inhibitor:  Synthesis of Salacinol and Its Stereoisomers,"Salacinol (4) is one of the active principles in the aqueous extracts of Salacia reticulata that are traditionally used in Sri Lanka and India for the treatment of diabetes. The syntheses of salacinol (4), the enantiomer of salacinol (5), and a diastereomer (7) are described. The synthetic strategy relies on the selective nucleophilic attack of 2,3,5-tri-O-benzyl-1,4-anhydro-4-thio-D- or L-arabinitol at C-1 of 2,4-O-benzylidene D- or L-erythritol-1,3-cyclic sulfate. The work serves to resolve the ambiguity about the exact structure of salacinol and establishes conclusively the structure of the natural product.",10.1021/jo001444g,2001-03-10,0.581440569694128
Synthesis,"Selective Reduction of Azides. Improved Preparation of α,α-Disubstituted Benzylamines",,10.1055/s-1978-24654,2002-04-05,0.5814344664945617
Organic Letters,Tandem Anionic 5-Exo Dig Cyclization/Claisen Rearrangement as an Efficient Route to Fused Polycyclic Ring Systems,"The scope and limitations of a tandem 5-exo dig cyclization/Claisen rearrangement sequence involving appropriately substituted 4-alkyn-1-ols as an efficient ""one-pot"" route to fused tricyclic ring systems is described. The reaction rates were found to be strongly dependent on the nature of the terminal substitutent of the triple bond. In some cases the entire sequence was found to proceed in good yield at temperatures as low as 115 degrees C.",10.1021/ol006139w,2000-06-21,0.5814325215252089
Angewandte Chemie International Edition,Concise Synthesis of (±)‐Myrioneurinol Enabled by Sequential [2+2] Cycloaddition/Retro‐Mannich Fragmentation/Mannich Reaction,Abstract A concise total synthesis of (±)‐myrioneurinol has been achieved in 14 steps. An efficient AgSbF 6 / t ‐BuCl‐catalyzed intramolecular [2+2] cycloaddition reaction of the alkynone‐tethered enamine was developed to prepare the highly strained cyclobutene. It was used in combination with a subsequent retro‐Mannich fragmentation/Mannich reaction to efficiently construct the tricyclic core of myrioneurinol.,10.1002/anie.202200085,2022-03-15,0.5814270295275794
Synlett,Stereoselective Synthesis of a Lactam Analogue of Brefeldin C,"A convergent, stereoselective synthesis of a brefeldin C lactam analogue is described. Novel features are application of the asymmetric iridium-catalyzed allylic substitution on a multigram scale for construction of the stereogenic centers C-9 as well as C-15 and an intermolecular Nozaki-Hiyama-Kishi reaction for introduction of the brefeldin enoate moiety.",10.1055/s-2008-1042899,2008-03-20,0.5814226119324473
Organic Letters,Iodocyclization of Chiral CF<sub>3</sub>-Allylmorpholinones: A Versatile Strategy for the Synthesis of Enantiopure α-Tfm-Prolines and α-Tfm-Dihydroxyprolines,An efficient iodocyclization reaction of a chiral Tfm-allylmorpholinone provides a straightforward route to alpha-Tfm-prolines and alpha-Tfm-dihydroxyprolines. The methodologies developed are particularly well adapted for gram-scale synthesis of enantiopure compounds.,10.1021/ol8024567,2008-12-02,0.5814214242324669
Tetrahedron,Convergent stereospecific total synthesis of Monocillin I and Monorden (or Radicicol),,10.1016/s0040-4039(00)77713-6,1992-02-01,0.5814193616581075
Angewandte Chemie International Edition,Bent π‐Conjugation within a Macrocycle: Asymmetric Total Syntheses of Spirohexenolides A and B,"Abstract Macrocycles with bent π‐conjugation motif are extremely rare in nature and synthetically daunting and anticancer haouamines and spirohexenolides were representative of such rare natural products with synthetically challenging bent π‐conjugation within a macrocycle. While the total synthesis of haouamines has been elegantly achieved, spirohexenolides remains an unmet synthetic challenge due to the highly strained bent 1,3,5‐triene conjugation within C15 macrocycle. Inspired by the chemical synthesis of cycloparaphenylenes (CPPs) and haouamines, herein we devise a synthetic strategy to overcome the highly strained bent 1,3,5‐triene conjugation within the macrocycle and achieve the first, asymmetric total synthesis of spirohexenolides A (&gt;20 mg) and B (&gt;50 mg). Our synthesis features strategic design of ring‐closing metathesis (RCM) macrocyclization followed by double dehydration to achieve the C15 macrocycle with the deformed nonplanar 1,3,5‐triene conjugation. In addition, we have developed a new enantioselective construction of highly functionalized spirotetronate fragment (northeast moiety) through RCM and Ireland–Claisen rearrangement. Our in vitro bioassay studies reveal that both spirohexenolides are cytotoxic against a panel of human cancer cells with IC 50 1.2–13.3 μM and spirohexenolide A is consistently more potent (up to 3 times) than spirohexenolide B, suggesting the importance of alcohol for their bioactivity and for medicinal chemistry development.",10.1002/anie.202316259,2023-11-22,0.5814180761562573
Tetrahedron,Asymmetric synthesis of γ-perfluoroalkyl(aryl) butyrolactones via organoboranes,,10.1016/j.tetlet.2003.11.050,2003-12-12,0.5814158798144474
Journal of the American Chemical Society,Biomimetic Synthesis of Antimalarial Naphthoquinones,"The total synthesis of naphthoquinone natural products isolated from the Bignoniaceae plant family is described. Pinnatal, isopinnatal, sterekunthals A and B, pyranokunthones A and B, and anthrakunthone have been prepared along the lines of a biosynthetic proposal involving pericyclic reactions as key steps. The first case of catalysis in oxa 6pi electrocyclizations is reported.",10.1021/ja050092y,2005-04-07,0.5814141783304108
Synthesis,"<i>N</i>-<i>tert</i>-Butyl-<i>N</i>-(2,2-dichlorovinyl)carbamoyl Chloride: A Novel Building Block for the Synthesis of Nitrogen Heterocycles","All articles of this category A synthesis of substituted 1,2,4-triazolidinones starting from N - tert -butyl- N -(2,2-dichlorovinyl)carbamoyl chloride ( 1 ) and hydrazine derivatives is reported. The reactions of 1 with ethylene-, phenylene- and propylenediamines followed by cyclizations yield the substituted cyclic ureas 6b-d , which may be used in the synthesis of bridged structures.",10.1055/s-1994-25572,1994-01-01,0.5814129553173875
Organic Letters,Biomimetic Synthesis of Cucurbalsaminone A,"Cucurbalsaminones, notable for their unique 5/6/3/6/5-fused pentacyclic triterpenoid structure, are potent inhibitors of P-glycoprotein. In this study, we propose a biosynthetic pathway starting from lanosterol, aiming to elucidate how these types of complex structures are synthesized by nature. Based on this, we present the first synthesis of cucurbalsaminone A in a biomimetic fashion. This synthesis emphasizes key steps including allylic oxidation/olefin isomerization, Lewis acid-mediated sequential migration of Me and H, and the oxa-di-π-methane rearrangement.",10.1021/acs.orglett.5c00440,2025-03-25,0.5814105737305099
Tetrahedron,Novel synthesis of oxa[9]helicenes by Lawesson’s reagent-mediated cyclization of helical quinone derivatives,,10.1016/j.tetlet.2011.06.033,2011-06-26,0.5814061122076402
Tetrahedron,"A short and efficient synthetic protocol for the synthesis of 5-substituted-4,6-dioxo-pyrrolo[2,3-d]pyrimidines",,10.1016/j.tetlet.2011.05.141,2011-06-13,0.5814037245270673
European Journal of Organic Chemistry,Synthesis of Functionalized Hydropentalenes by an Asymmetric Deprotonation/Alkylation Strategy,"Abstract The functionalization of differently substituted hydropentalenone derivatives 9 , derived from the Weiss diketone ( 8 ) by enantioselective deprotonation in the presence of lithium ( R , R )‐bis(1‐phenylethyl)amide/LiCl ( 11· LiCl) as the chiral base is described. In the first route the resulting enolate was treated directly with alkyl halides as electrophiles to give the target α‐alkylhydropentalenones 12 , whereas in the second route the enolate was trapped as one of the triethylsilyl enol ethers 17 , from which the enolate was regenerated by treatment with MeLi prior to alkylation with alkyl halides. The substituents on 9 seemed to influence which strategy is favored: for the OTBS‐substituted hydropentalenone 9a the direct deprotonation/alkylation is preferred, whereas for the acetal‐substituted hydropentalenone 9b the silyl enol ether route is more suitable. In all cases the α‐alkylated hydropentalenones 12 and 15 were isolated with good diastereoselectivities.",10.1002/ejoc.200901154,2010-01-12,0.5813959545784227
Tetrahedron,"Synthesis of antiviral nucleosides from crotonaldehyde. Part 3.1,2 total synthesis of didehydrodideoxythymidine (d4T)",,10.1016/s0040-4039(00)74799-x,1992-06-01,0.5813958234294048
Tetrahedron,A simple route to the 8-oxabicyclo[3.2.1]octyl and 9-oxabicyclo[3.3.1]nonyl systems. Synthesis of the 8-oxa analog of cocaine.,,10.1016/s0040-4039(01)86612-0,1979-01-01,0.5813953196437391
Tetrahedron,Efficient synthesis of carbapenems via the oxalimide cyclization. Manipulation of protecting groups at the oxalimide stage,,10.1016/0040-4039(95)00854-6,1995-06-01,0.581392120247816
Journal of Organic Chemistry,Synthesis of Axinohydantoins,"A short synthesis of the hydantoin-containing marine sponge metabolites axinohydantoins is described. A key feature of the synthesis is a putative biomimetic, intramolecular cyclization of alpha-functionalized imidazolone 5, which affords the tricyclic pyrroloazepinone framework comprising 6. In addition, the conversion of imidazolones to alpha,beta-unsaturated hydantoins is outlined and represents a new approach to these heterocyclic systems.",10.1021/jo020063v,2002-05-10,0.5813880922719683
Tetrahedron,New synthesis of isoxazolidines from the selenium-induced cyclization of O-allyl hydroxylamines,,10.1016/0040-4039(94)02201-l,1995-01-01,0.5813868077652784
European Journal of Organic Chemistry,A Unified Synthetic Strategy for the Indolopyridine Alkaloid Group,"Thermal or acetyl chloride induced cyclization of bromoenamide 10 affords the pentacyclic derivative 12 with high yield and regioselectivity. From this common synthetic intermediate, palladium-catalyzed reactions allow the total synthesis of indolopyridine alkaloids 1–6.",10.1002/(sici)1099-0690(199902)1999:2<373::aid-ejoc373>3.0.co;2-z,1999-02-01,0.5813850173308759
Journal of Organic Chemistry,"Total Synthesis of Linear Coumarniolignoids (+) and (−)-Sapiumin C, (−)-Moluccanin, and (−)-Hemidesminine","Coumarinolignoids (CLs) are a class of natural products isolated from a diverse range of plant species. Due to their unique structural scaffold, they exhibit a wide range of interesting biological activities including hepatoprotective, antitumor, anti-inflammatory, and antioxidant activities among others. In this research, key intermediate 10 was used to stereoselectively synthesize CLs (7′ S,8′ S )- and (7′ R,8′ R )-sapiumin C 1 and 2, (7′ S,8′ S )-moluccanin 3, and (7′ S,8′ S ) hemidesminine 4 for the first time, establishing a versatile synthetic method for the stereoselective synthesis of linear CLs. The developed method includes a Mitsunobu coupling, a modified Miyaura arylation via a rhodium catalyst, and an acid-catalyzed cyclization in key bond-forming steps. The developed synthetic route allows the synthesis of both enantiomers of a given natural product from the same chiral pool reagent ( S )-solketal while allowing easy variation of aromatic substitution and hydroxymethyl/allylhydroxymethyl moieties that are common in this class of natural products.",10.1021/acs.joc.3c00292,2023-04-18,0.5813735102139187
Angewandte Chemie International Edition,Total Synthesis of Lissodendoric Acid A,We describe a full account of our synthetic strategy leading to the first total synthesis of the manzamine alkaloid lissodendoric acid A . These efforts demonstrate that strained cyclic allenes are valuable synthetic building blocks and can be employed efficiently in total synthesis.,10.1002/anie.202406676,2024-05-02,0.5813715987871805
Journal of Organic Chemistry,Asymmetric Modular Synthesis of a Semirigid Dipeptide Mimetic by Cascade Cycloaddition/Ring Rearrangement and Borohydride Reduction,"A new semirigid dipeptide mimetic was prepared on multigram scale, in good yield, and in a stereocontrolled way, starting from commercially available and unexpensive reagents, i.e., N-benzylpiperidone, tosyl azide, and proline methyl ester. The optimized multicomponent process consisted of a cascade click cycloaddition and a ring rearrangement reaction, followed by a reductive step. Theoretical calculations were performed to elucidate the reaction mechanism and support the stereochemical outcome of the reduction. Finally, the new scaffold was used for the preparation of model peptidomimetics, whose β turn conformation was confirmed by dynamic NMR experiments.",10.1021/jo500237j,2014-03-17,0.5813648571573717
Tetrahedron,A highly efficient stereoselective synthesis of β-lactams,,10.1016/j.tetlet.2016.12.033,2016-12-12,0.5813596562015811
Tetrahedron,A highly efficient stereoselective synthesis of (Z)- and (E)-allyl iodides from Baylis–Hillman adducts,,10.1016/j.tetlet.2005.09.097,2005-10-06,0.5813596562015811
Tetrahedron,"An efficient, highly stereoselective synthesis of (+)-castanospermine",,10.1016/s0040-4039(00)97611-1,1990-01-01,0.5813596562015811
Organic Letters,"Total Synthesis of Biselide E, a Marine Polyketide","The total synthesis of biselide E, a marine polyketide isolated from the Okinawan ascidian, has been accomplished. The highlight of this approach is the use of the β-elimination reaction of the chloroacetoxy group for the construction of an unstable six-membered α,β,γ,δ-unsaturated lactone portion at the late stage of the total synthesis.",10.1021/acs.orglett.7b03009,2017-10-11,0.5813578904646765
Organic Letters,Synthesis of a Novel Chiral Binaphthyl Phospholane and Its Application in the Highly Enantioselective Hydrogenation of Enamides,"[formula: see text] A new chiral phosphine, (R,R)-1,2-bis[(R)-4,5-dihydro-3H-dinaphtho[2,1- c:1',2'-e]phosphepino]benzene [abbreviated as (R,R)-binaphane] was prepared on the basis of a practical route from a readily accessible enantiomerically pure binaphthanol. This ligand possesses both binaphthyl chirality and phospholane functionality. Excellent enantioselectivities (95-99.6% ee) have been observed in hydrogenation of an isomeric mixture of (E)- and (Z)-beta-substituted-alpha-arylenamides by using a Rh-binaphane catalyst. These enantioselectivities are the highest reported to date for this transformation.",10.1021/ol991074m,1999-10-20,0.5813564055477576
Journal of the American Chemical Society,Total Synthesis of (+)-Euphorikanin A via an Atropospecific Cascade,"High Resolution Image Download MS PowerPoint Slide A total synthesis of the ingenane-derived diterpenoid (+)-euphorikanin A is described. Key to the strategy is a stereocontrolled one-pot sequence consisting of transannular aldol addition reaction, hemiketal formation, and subsequent semipinacol rearrangement that efficiently leads to the complete euphorikanin skeleton. Atroposelective ring-closing olefin metathesis proved critical for the stereospecific cascade, leading to formation of a ( Z )-bicyclo[7.4.1]tetradecenone core. An additional salient feature of the route is pyrolysis of a bis-methylxanthate to cleanly furnish the natural product.",10.1021/jacs.3c11000,2023-12-05,0.5813558634087649
Tetrahedron,"Resolution-free route to chiral 2,2′-bis(pyridin-2-yl)-1,1′-binaphthyl ligand: photochemical CpCo(CO)2-mediated cycloaddition of enantiopure 2,2′-dicyano-1,1′-binaphthyl with diynes",,10.1016/j.tetlet.2004.02.155,2004-03-28,0.5813521106354925
Journal of the American Chemical Society,Explorations in Organic Chemistry Leading to the Total Synthesis of (±)-Gelsemine,"The total synthesis of (+/-)-gelsemine (1) is described. A defining phase of the effort involved recourse to a strategic oxetane ring (see compound 25). It was constructed anticipating an intramolecular displacement of the carbon (C17)-oxygen (O4) bond (see product 48). A key intermediate in the stereospecific elaboration of the oxetane linkage was enone 22, which was susceptible to two beta-face attacks leading to 24 and, thence, 25. Three sigmatropic rearrangements were employed in building the bridgehead (C20) and the spiroanilide (C7) quaternary centers en route to gelsemine.",10.1021/ja0204675,2002-07-27,0.5813515964173149
Synthesis,"Total Synthesis of the Natural Carbazoles O-Demethylmurrayanine and Murrastanine A, and of a C4,C4′ Symmetric Murrastanine A Dimer from N-Phenyl-4,5-dimethylene-1,3-oxazolidin-2-one","Abstract The synthesis of natural carbazoles O-demethylmurrayanine and murrastanine A starting from the title exo-heterocyclic diene­ is described. In the synthesis of murrastanine A, its symmetric C4,C4′ dimer can be obtained as the sole product under rather mild conditions. In all cases, the key intermediate is the same diarylamine. The carbazole nucleus is obtained through a Pd-promoted cyclization of the appropriate diarylamine. For the synthesis of O-demethylmurrayanine, the cyclization takes place on a silylated derivative. The crystal structures of murrayanine, two diarylamines, and two non-natural carbazole intermediates are also presented.",10.1055/a-1385-9052,2021-02-08,0.5813444954889564
Journal of Organic Chemistry,"Synthesis of Dithieno[2,3-b:4â²,3â²-d]siloles and Their Selective Bromination",,,2012-01-01,0.5813442899030734
Journal of Organic Chemistry,"Novel Approach to the Zaragozic Acids. Enantioselective Total Synthesis of 6,7-Dideoxysqualestatin H5","The total synthesis of 6,7-dideoxysqualestatin H5 (3) has been completed by a concise approach that features the stereoselective intramolecular vinylogous aldol reaction of the furoic ester 25a to give 30 or its trimethylsilyl ether derivative 34, which possess the requisite absolute stereochemistry at C(3)-C(5) of 3. Compound 34 was reduced to the saturated bislactone 39, and the C(1) side chain subunit 47 was introduced leading to a mixture of the hemiacetals 48 and the corresponding ketone 49. When this mixture was stirred with methanolic acid, transketalization occurred to give a mixture of 50 and the spirocyclic methyl acetals 51a,b. Oxidation of the primary alcohol group in 50 followed by saponification of the two remaining ester groups gave 3. The longest linear sequence in the synthesis commences with commercially available erythronolactone (26) and requires 17 chemical steps with only 10 isolated intermediates.",10.1021/jo011157s,2002-05-10,0.5813391940792599
Organic Letters,"Straightforward and Highly Efficient Catalyst-Free One-Step Synthesis of 2-(Purin-6-yl)acetoacetic Acid Ethyl Esters, (Purin-6-yl)acetates, and 6-Methylpurines through S<sub>N</sub>Ar-Based Reactions of 6-Halopurines with Ethyl Acetoacetate","A novel approach to the synthesis of purines bearing functionalized carbon substituents or methyl in position 6 was developed. Under different reaction conditions, 6-halopurine derivatives could react with ethyl acetoacetate efficiently to yield 2-(purin-6-yl)acetoacetic acid ethyl esters, (purin-6-yl)acetates and 6-methylpurines respectively. No metal catalyst and ligand were required.",10.1021/ol9002256,2009-03-18,0.5813324744961892
Tetrahedron,"Synthesis of dipyrrolo[3,4-a:3,4-c]carbazoles: new kinase inhibitors",,10.1016/j.tetlet.2013.12.027,2013-12-15,0.5813232830193765
Tetrahedron,"Synthesis of benzyl (6S)-1,3-dichloro-4-oxo-4,6,7,8-tetrahydro-pyrrolo[1,2-a]pyrazine-6-carboxylic ester, a new conformationally constrained peptidomimetic derivative",,10.1016/s0040-4039(02)00574-9,2002-05-01,0.5813211747419483
Organic Letters,Enantioselective Synthesis of Fluorinated Indolizidinone Derivatives,"High Resolution Image Download MS PowerPoint Slide The enantioselective synthesis of fluorinated indolizidinone derivatives has been developed. The process involved an enantioselective intramolecular aza-Michael reaction of conjugated amides bearing a pendant α,β-unsaturated ketone moiety, catalyzed by the ( S )-TRIP-derived phosphoric acid, followed by dimethyltitanocene methylenation and ring closing metathesis (RCM). Final indolizidine-derived products comprise a fluorine-containing tetrasubstituted double bond generated by the RCM reaction, which is a challenging task. The whole synthetic sequence took place in acceptable overall yields with excellent enantioselectivities.",10.1021/acs.orglett.3c00903,2023-05-01,0.5813191860815674
Synthesis,Revision of the Structure and Total Synthesis of Topsentin C,"An efficient synthetic approach to access (indol-3-yl)ethane-1,2-diamines with a protecting group at the indole N atom from readily available 3-(2-nitrovinyl)indoles is reported. This approach includes solvent-free conjugate addition of O-pivaloylhydroxylamines to 1-Boc-3-(2-nitrovinyl)indoles followed by mild reduction of the adducts. The obtained (indol-3-yl)ethane-1,2-diamines are convenient synthetic precursors for several classes of marine alkaloids. The first total synthesis of racemic topsentin C, a secondary metabolite from Hexadella sp., based on this approach is reported. The initially proposed structure for topsentin C has been revised.",10.1055/s-0036-1588731,2017-02-23,0.5813172423635103
Tetrahedron,"Efficient route to pre-organized and linear polyaminopolycarboxylates: Cy-TTHA, Cy-DTPA and mono/di- reactive, tert -butyl protected TTHA/Cy-TTHA",,10.1016/j.tetlet.2017.02.056,2017-02-20,0.5813078583987117
European Journal of Organic Chemistry,Synthesis and Optical Properties of Difluorobora‐<i>s</i>‐diazaindacene Dyes with Trifluoromethyl <i>meso‐</i>Substituents,"Abstract A series of meso ‐CF 3 ‐4,4‐difluoro‐4‐bora‐3a,4a‐diaza‐ s ‐indacene (BODIPY) dyes with aryl and hetaryl substituents at the C‐3 and C‐5 positions, both symmetric and asymmetric, have been synthesized in 36–90 % yields by a new strategy involving as the key step the condensation of 2,2,2‐trifluoro‐1‐(5‐arylpyrrol‐2‐yl)‐1‐ethanols with diverse 2‐arylpyrroles. The starting 2,2,2‐trifluoro‐1‐(5‐arylpyrrol‐2‐yl)‐1‐ethanols are easily prepared by reduction of the available 2‐trifluoroacetyl‐5‐arylpyrroles. The synthesized dyes fluoresce in a longer wavelength region (626–698 nm) with high quantum yield (0.84–0.99).",10.1002/ejoc.201300212,2013-05-10,0.5813052549072288
Journal of Organic Chemistry,"Total Synthesis of Natural PI-091, a New Platelet Aggregation Inhibitor of Microbial Origin","The total synthesis of a new platelet aggregation-inhibiting gamma-lactam PI-091 (1) gave a 1:1 diastereomeric mixture at the gamma-ketal carbon. The high-yielding aldol reaction of an appropriately protected 1,3,4-trihydroxy-4-methyldecan-2-one 42, prepared from D-glucose, with the kinetically generated enolate of 3-methyl-2-butanone provided 43. The resulting diastereomeric mixture of the aldol adduct 43 was converted to a 2,4-alkylated furan 45 via an intramolecular ketalization followed by dehydration. The addition of a singlet oxygen to the alpha-trimethylsilylated furan 48derived from 45 under photochemical conditions efficiently provided an alpha,gamma-dialkylated gamma-hydroxy gamma-lactone 47. The transformation of methyl ketal 52 prepared from 47 into gamma-hydroxy gamma-lactam 53 was achieved by exposure to liquid ammonia in MeOH. The total synthesis of 1 was achieved from 52 through the Dess-Martin periodinane oxidation of the secondary hydroxy group in the side chain. The present total synthesis revealed that the stereogenic carbon center in the side chain in natural 1 is S.",10.1021/jo951897z,1996-01-01,0.5813025648919403
Synlett,"A New Approach to the Synthesis of 4-Thio-1,2-Dideoxyribose","All articles of this category A novel approach to the synthesis of racemic 4-thio-1,2-deoxyribose (1) is described. Thus, commercially available γ-thiobutyrolactone is converted to the thiolenol triflate (3) and then to the key 5-(hydroxymethyl)-2,3-dihydrothiophene (2). Hydroboration followed by oxidative work up gives the desired product (1) in four steps. Thiosugar - vinyl stannane - vinyl triflate",10.1055/s-1995-5165,1995-10-01,0.5813022461207283
Synlett,A Novel Cyclisation Strategy for the Synthesis of Lactonamycin: A New Route to Highly Functionalised Heterocyclic Rings,A novel thermal cascade reaction equivalent to the well-known [2+2+2] cycloaddition has been developed which is clean and reliable and does not involve the use of metal ions. This highly efficient method has been used to construct a model for the synthesis of the antibiotic lactonamycin. The utility of this new sequence for the formation of furans is also reported.,10.1055/s-2006-951542,2006-11-23,0.5812952947609115
Organic Letters,"Synthesis of 2,5-Disubstituted 6-Azaindoles from Substituted Aziridines via Intramolecular Cyclization","A new and efficient preparation of pharmacologically and biologically important 2,5-disubstituted 6-azaindoles was achieved from cyclizations of aziridin-2-yl dipropargylic alcohols as adducts of two propargyl groups to ethyl 1-benzylaziridine-2-carboxylate. The sequential cyclizations include pyrrole formation and a novel base-catalyzed intramolecular acetylenic Schmidt reaction.",10.1021/ol301187s,2012-06-05,0.5812932532873817
Tetrahedron,Efficient synthetic method of Psammaplin A,,10.1016/j.tetlet.2012.05.149,2012-06-07,0.5812930798796336
European Journal of Organic Chemistry,"Asymmetric Synthesis of 3,4,6‐Trisubstituted 2,5‐Diketopiperazines by Using Dynamic Kinetic Resolution of α‐Bromo Tertiary Acetamides","Abstract A new and efficient method for the asymmetric synthesis of 3,4,6‐trisubstituted 2,5‐diketopiperazines has been developed. The dynamic kinetic resolution of L ‐amino‐acid‐derived α‐bromo tertiary amides in the nucleophilic substitution reaction with p ‐anisidine and a subsequent deprotection‐cyclization process provides rapid access to diverse cis ‐2,5‐diketopiperazines 5a – 5o and proline‐containing trans ‐2,5‐diketopiperazines 5p – 5t in enantiomerically pure form in 45–67 % overall yields.",10.1002/ejoc.201301936,2014-03-06,0.581290358677039
Tetrahedron,A straightforward and practical formal synthesis of lavendamycin ethyl ester,,10.1016/s0040-4039(00)76244-7,1994-02-01,0.5812883806578337
Organic Letters,Enantioselective Synthesis of 10-<i>e</i><i>pi</i>-Anamarine via an Iterative Dihydroxylation Sequence,"[reaction: see text] The enantioselective syntheses of 10-epi-anamarine and 5,10-epi,epi-anamarine have been achieved in 13 to 14 steps. The route relies upon an enantio- and regioselective Sharpless dihydroxylation of either dienoates or trienoates to establish the C-8 to C-11 stereochemistry. A diastereoselective Leighton allylation established the desired C-5 stereochemistry. The route also relies upon a ring-closing metathesis to establish the alpha,beta-unsaturated lactones.",10.1021/ol047322i,2005-02-22,0.58128478962977
Angewandte Chemie International Edition,Total Synthesis of Crocagin A,"Crocagin A (1) combines an attractive molecular structure with an unusual biosynthesis and bioactivity. An efficient synthesis of crocagin A is presented that hinges on an early formation of the heterotricyclic core, an electrophilic amination, and the stereoselective hydrogenation of a tetrasubstituted double bond. This synthesis confirms the absolute configuration of crocagin A and provides access to the natural product and derivatives thereof for further biological testing.",10.1002/anie.201612641,2017-08-16,0.5812821333336289
Journal of Organic Chemistry,Synthesis of 1-Arylmethyl-2-(2-cyanoethyl)aziridines and Their Rearrangement into Novel 2-(Aminomethyl)cyclopropanecarbonitriles,"1-Arylmethyl-2-(bromomethyl)aziridines were transformed into novel 2-(2-cyanoethyl)aziridines upon treatment with alpha-lithiated trimethylsilylacetonitrile in THF in an efficient and straightforward approach. The latter aziridines underwent ring opening by reaction with benzyl bromide in acetonitrile, affording 5-amino-4-bromopentanenitriles through a regiospecific ring opening of intermediate aziridinium salts by bromide. Further elaboration of these gamma-bromonitriles resulted in the synthesis of novel 2-[N,N-bis(arylmethyl)aminomethyl]cyclopropanecarbonitriles in high yields by means of a 1,3-cyclization protocol upon treatment with KOtBu in THF.",10.1021/jo701302a,2007-08-17,0.5812784855085273
Organic Letters,Total Syntheses of (+)-Marrubiin and (−)-Marrulibacetal,A stereoselective total synthesis of (+)-marrubiin has been accomplished starting from a chiral building block via the CyNH2-promoted Pauson-Khand reaction (PKR) followed by oxidative cleavage of the resultant cyclopentenone ring. Two successive oxidations and internal transacetalization culminated in the total synthesis of the antispasmodic labdane diterpenoid (-)-marrulibacetal.,10.1021/acs.orglett.6b01602,2016-06-24,0.5812714007713566
Tetrahedron,"Isolation and structure of flutimide, a novel endonuclease inhibitor of influenza virus",,10.1016/0040-4039(95)00213-v,1995-03-01,0.5812679301396441
Tetrahedron,"A general approach to -carbapenem antibiotics. Enantioselective synthesis of key intermediates for (+)-PS-5, (+)-PS-6, and (+)-thienamycin",,10.1016/s0040-4039(00)81369-6,1983-01-01,0.5812572521962411
Tetrahedron,"A new enantioselective synthesis of (4S, 5S)-5-(N-Boc)-amino-6-cyclohexyl-4-hydroxy-hexanoic acid lactone, a hydroxyethylene dipeptide isostere precursor",,10.1016/0040-4039(91)80024-z,1991-01-01,0.5812551870695957
Tetrahedron,A novel highly enantio- and diastereoselective synthesis of vitamin E side-chain,,10.1016/j.tetlet.2014.12.081,2014-12-20,0.5812523095130717
Synlett,From Aziridines to Oxazolines and Thiazolines: The Heterocyclic Route to Thiangazole,"All articles of this category Since its isolation in 1991, the polyazole natural product thiangazole has become a popular target for total synthesis due to its challenging array of heterocyclic segments and its reported potent antiviral activity. The synthetic activity toward thiangazole is reviewed and a novel approach that takes advantage or aziridine and oxazoline intermediates en route to thiazolines is presented. Staudinger reaction - α-methyl serine - α-methyl cysteine - thiolysis - Burgess reagent",10.1055/s-1997-681,2004-03-22,0.5812515596284863
Tetrahedron,Synthesis and structure elucidation of a new isoquinolinium inner salt,,10.1016/j.tetlet.2009.05.099,2009-05-31,0.58124917065865
Journal of the American Chemical Society,Intramolecular Cyclobutadiene Cycloaddition/Cyclopropanation/Thermal Rearrangement:  An Effective Strategy for the Asymmetric Syntheses of Pleocarpenene and Pleocarpenone,"The first total synthesis of the guaiane sesquiterpene natural products pleocarpenone and pleocarpenene is described. An intramolecular cycloaddition of cyclobutadiene, followed by cyclopropanation and thermal fragmentation of the resulting highly strained intermediate, is the strategy used to achieve this synthesis. The asymmetric route allowed for confirmation of the absolute stereochemistry of these natural products.",10.1021/ja0674340,2006-12-22,0.5812490691754142
Synlett,A Simple and very Efficient Route to New Chiral Ferrocenyl Diamines via Diastereoselective Alkylation,"All articles of this category A new family of chiral ferrocenyl diamines bearing one planar chirality and one or two stereogenic centers has been easily synthesized starting from 2-( N , N -dimethylaminomethyl)ferrocenylcarboxaldehyde ( 1 ) via a highly diastereoselective step. All diamines were obtained in high diastereomeric excesses and optical purities (de and ee >98%) and in 80% to 85% yields. diamines - diastereoselectivity - N , N -dimethylaminomethylferrocene - imines - organometallic reagents",10.1055/s-2001-9693,2001-12-31,0.5812483748957659
Angewandte Chemie International Edition,The Indium‐Mediated Selective Introduction of Allenyl and Propargyl Groups at the C4‐Position of 2‐Azetidinones and the AuCl<sub>3</sub>‐Catalyzed Cyclization of 4‐Allenyl‐2‐azetidinones,"Bicyclic β lactams are obtained by the two-step procedure shown in the scheme. Alternatively, with the help of organoindium reagents, allenyl and propargyl groups are introduced at the C4-position of 2-azetidinones. R1=H, 1R-(tert-butyldimethylsilyloxy)ethyl (TBSO(CH3)CH); R2=H, methyl, ethyl, n-butyl, phenyl, THPOCH2, trimethylsilyl, 2-naphthyl; R3=H, methyl, phenyl; R4=H, methyl.",10.1002/anie.200462512,2005-02-16,0.5812441263516999
Synthesis,A New and Simple Synthesis of Triacetic Acid Lactone-3-carboxylic Acid (3-Carboxy-4-hydroxy-6-methyl-2-pyrone),,10.1055/s-1975-23872,1975-01-01,0.5812440842698451
Tetrahedron,An efficient stereospecific total synthesis of (±) terrein,,10.1016/s0040-4039(01)93040-0,1981-01-01,0.5812440707811383
Angewandte Chemie International Edition,Intramolecular Radical Aziridination of Allylic Sulfamoyl Azides by Cobalt(II)‐Based Metalloradical Catalysis: Effective Construction of Strained Heterobicyclic Structures,"Cobalt(II)-based metalloradical catalysis (MRC) has been successfully applied for effective construction of the highly strained 2-sulfonyl-1,3-diazabicyclo[3.1.0]hexane structures in high yields through intramolecular radical aziridination of allylic sulfamoyl azides. The resulting [3.1.0] bicyclic aziridines prove to be versatile synthons for the preparation of a diverse range of 1,2- and 1,3-diamine derivatives by selective ring-opening reactions. As a demonstration of its application for target synthesis, the metalloradical intramolecular aziridination reaction has been incorporated as a key step for efficient synthesis of a potent neurokinin 1 (NK1 ) antagonist in 60 % overall yield.",10.1002/anie.201605238,2016-08-11,0.5812436787128125
Organic Process Research & Development,Practical Synthesis of a 6-Triazolylazabicyclo[3.1.0]hexane,"We describe a practical, scalable synthesis of an advanced heterocyclic intermediate, (1 R,5 S,6 s )-6-(4 H -1,2,4-triazol-4-yl)-3-azabicyclo[3.1.0]hexane. A robust synthetic sequence based on a Kulinkovich–de Meijere pyrroline cyclopropanation followed by transamination of N, N ′-dimethylformamide azine with the resultant amine was developed to supply >18 kg of the target triazolyl azabicycle with 98 wt % purity in its free base form. Reaction conditions and isolation methods for the key 1,2,4-triazole formation step were explored to minimize undesired reaction pathways and to increase the purity of the product. Additionally, at several stages different freebasing methods were implemented that addressed the high water solubility of the associated nitrogen-rich compounds.",10.1021/acs.oprd.8b00101,2018-06-01,0.5812419034381443
Synthesis,The Synthesis of Amino Acid Bridged Dicatechol Derivatives,"All articles of this category Amino acid bridged dicatechol ligands 1 a - e are synthesized by a stepwise coupling procedure. First 2,3-dimethoxybenzoic acid ( 2 ) is coupled with the amino acid ( 3 a - e ) followed by a second coupling step of the obtained derivatives 4 a - e with 2,3-dimethoxybenzyl amine ( 5 ). As coupling reagents for the amide bonds either DDC/NHS or EDC/HOBt are used. In the final step of the reaction sequence the methyl ethers of the ligand precursors 6 a - e are potential building blocks for metallo-supramolecular chemistry. amino acids - catechol - ligands - amides - supramolecular chemistry",10.1055/s-2001-11438,2001-01-01,0.5812411723335986
Synlett,A Concise Stereoselective Synthesis of Epibatidine Employing Conjugate Addition to an Alkenyl Sulfone Intermediate as the Key Step,"All articles of this category A new synthesis of racemic epibatidine has been achieved, which involves conjugate addition of a metallated 2-methoxypyridine derivative to a suitably protected azabicyclic alkenyl sulfone as the key step. epibatidine - alkaloid - cycloaddition - alkenyl sulfone",10.1055/s-1997-3225,1997-05-01,0.5812377352547649
Synlett,A New Short Cut Route to 3-Norcephalosporins<sup>1</sup>,"All articles of this category 3-Norcephems 1 bearing heteroatom substituents directly attached to C(3)-position were prepared starting from penicillin G through a new short cut route involving Michael addition of amines, azide or thiols to allenic esters 6 , 2-[2-oxo-3-phenylacetylamino-4-(phenylsulfonylthio)azetidin-1-yl]-2,3-butadienoic acid esters, and sequential ring closure to the six-membered ring.",10.1055/s-1991-20912,1991-01-01,0.5812350560082111
Journal of Organic Chemistry,"Total Synthesis of Aqabamycin G, a Nitrophenyl Indolylmaleimide Marine Alkaloid from <i>Vibrio sp</i>. WMBA",The first total synthesis of the marine alkaloid aqabamycin G is disclosed. The synthetic sequence involved the stepwise addition to maleimide of an indole motif and a substituted diazo-benzenoid unit derived from acetaminophen. An alternative strategy using a protected phenol is also reported.,10.1021/acs.joc.2c00063,2022-03-24,0.5812295963544434
Tetrahedron,New acyl anion equivalent. A short route to the enol lactam intermediate in cytochalasin synthesis,,10.1016/s0040-4039(01)92517-1,1981-01-01,0.5812287121231934
Tetrahedron,Synthesis in the indole series viii (1): a novel approach to indoloquinolizidines through alkylation-cyclization of an enamine derived from tryptamine,,10.1016/s0040-4039(00)86779-9,1982-01-01,0.5812276724279908
Tetrahedron,Highly enantiocontrolled total synthesis of (-)-protoemetinol,,10.1016/s0040-4039(00)80653-x,1988-01-01,0.5812275710423445
Tetrahedron,A highly stereocontrolled total synthesis of (+)-biotin from l-cysteine,,10.1016/s0040-4039(02)00537-3,2002-04-01,0.5812275710423445
Tetrahedron,Concise total synthesis of honokiol via Kumada cross coupling,,10.1016/j.tetlet.2014.04.084,2014-05-02,0.5812260887807076
Journal of Organic Chemistry,Regiospecific N9 Alkylation of 6-(Heteroaryl)purines:  Shielding of N7 by a Proximal Heteroaryl C−H<sup>1</sup>,"Purine alkylations have been plagued with formation of mixtures of N9 (usually desired), N7, and other regioisomers. We have developed methods for synthesis of 6-(azolyl)purine derivatives whose X-ray crystal structures show essentially coplanar conformations of the linked azole-purine rings. Such ring orientations position the C-H of the azole above N7 of the purine, which results in protection of N7 from alkylating agents. Treatment of 6-(2-butylimidazol-1-yl)-2-chloropurine (9) with sodium hydride in DMF followed by addition of ethyl iodide resulted in exclusive formation of 6-(2-butylimidazol-1-yl)-2-chloro-9-ethylpurine (10), whereas identical treatment of 2-chloro-6-(4,5-diphenylimidazol-1-yl)purine (11) produced a regioisomeric mixture 12/13 (N9/N7, approximately 5:1). The linked imidazole and purine rings are coplanar in 9 (the butyl side chain is extended away from the purine ring and C-H is over N7) but are rotated approximately 57 degrees in 11, and the more bulky azole substituent in 11 did not prevent formation of the minor N7 regioisomer 13. Access to various regioisomerically pure 9-alkylpurines is now readily available.",10.1021/jo061759h,2006-10-18,0.5812065181067262
Tetrahedron,Photodifluoramination of CF3C15N: Evidence for intermediate formation of an alkylfluorodiazene,,10.1016/s0040-4039(01)86890-8,1973-01-01,0.581204500274205
Tetrahedron,The nitrene intermediate in the photo-formation of carbazole from 2-azidobiphenyl,,10.1016/s0040-4039(01)84130-7,1966-01-01,0.581204500274205
Synlett,Synthetic routes to novel homochiral sulfenyl sulfonium salts and their use as potential enantioselective sulfenylating agents. Asymmetric synthesis<i>via</i>homochiral thiiranium ions.,All articles of this category The synthesis of a variety of novel sulfenyl sulfonium salts is described from known and novel homochiral sulfides and dimethyl(methylthio)sulfonium tetrafluoroborate (DMTSF). Preliminary results of asymmetric alkene sulfenylation are also given.,10.1055/s-1994-22947,1994-01-01,0.5812023849692659
Angewandte Chemie International Edition,Asymmetric Triple Relay Catalysis: Enantioselective Synthesis of Spirocyclic Indolines through a One‐Pot Process Featuring an Asymmetric 6π Electrocyclization,"A rare example of a one-pot process that involves asymmetric triple relay catalysis is reported. The key step is an asymmetric [1,5] electrocyclic reaction of functionalized ketimines. The substrates for this process were obtained in situ in a two-step process that involved the hydrogenation of nitroarenes with a Pd/C catalyst to yield aryl amines and their subsequent coupling with isatin derivatives in a Brønsted acid catalyzed ketimine formation reaction. The electrocyclization was catalyzed by a bifunctional chiral Brønsted base/hydrogen bond donor catalyst. The one-pot process gave the desired products in good yields and with excellent enantioselectivity.",10.1002/anie.201407677,2014-10-14,0.5811985302695154
Organic Process Research & Development,Process Development and Preparation of 2-Deoxyparaherquamide:  Implementation of a Selective Reduction of Secondary Amides on a Kilogram Scale,"The preparation of 2-deoxyparaherquamide, PNU-141962, is accomplished through the indirect selective reduction of a secondary amide in the presence of a tertiary amide. The kilogram-scale process is safe and robust and allows for the isolation of analytically pure material in high overall yield without a chromatographic purification.",10.1021/op010233q,2002-02-08,0.5811884892646222
Organic Process Research & Development,A Large Scale Process for the Preparation of Thymitaq,"The large scale manufacturing of the anticancer agent 2-amino-6-methyl-5-(pyridin-4-ylsulfanyl)-3 H -quinazolin-4-one dihydrochloride (thymitaq) from 6-bromo-5-methylanthranilic acid is described. The chemical route consists of two chemical steps: formation of a bromoquinazolinone and a copper-mediated Ullman-like coupling between 4-mercaptopyridine and the bromoquinazolinone. During process development, sodium hydride was replaced with sodium hydroxide and a method for removal of copper, based on 2,4,6-trimercapto- s -triazine, was developed. A number of purification operations were performed to ensure a product of pharmaceutical quality.",10.1021/op800181e,2008-10-25,0.5811858261462297
European Journal of Organic Chemistry,"Synthesis of 2‐Ethyl‐19‐<i>nor</i> Analogs of 1α,25‐Dihydroxyvitamin D<sub>3</sub>","Abstract The synthesis of two new A‐ring precursors, useful for the convergent assembly of 2α‐ethyl and 2β‐ethyl derivatives of 19‐ nor ‐1α,25‐dihydroxyvitamin D 3 , is described. These building blocks were prepared in 14 steps from quinic acid, which led to a new and practical synthesis of 2α‐ethyl‐14‐ epi ‐19‐ nor ‐20‐ epi ‐23‐yne‐1,25(OH) 2 D 3 , an analog that shows a remarkably low calcemic effect in mice, while retaining the ability to promote cell differentiation and to inhibit cell proliferation in a number of human cancer cell lines.",10.1002/ejoc.201201261,2012-12-10,0.5811833447684686
Journal of Organic Chemistry,"Synthesis of N-Functionalized/NH-Multisubstituted Indoles, Thienopyrroles, Pyrroloindoles, and Pyrazolopyrroles via Sequential One-Pot Base-Mediated and Copper-Catalyzed Inter- and Intramolecular Amination of 2-[2-Bromo(het)aryl]-3-(het)aryl-3-(methylthio)acrylonitriles","A novel, efficient route to substituted 1-N-(het)aryl/NH-2-(het)aryl-3-cyanoindoles and related pyrrolo-fused heterocycles such as thienopyrroles, pyrroloindoles, and pyrazolopyrroles has been reported. The overall protocol involves sequential cycloamination of readily available 2-[2-bromo(het)aryl]-3-(het)aryl-3-(methylthio)acrylonitrile precursors with primary amines or amides via two key C-N bond-forming processes, one base-mediated intermolecular and the other Cu-catalyzed intramolecular arylamination leading to N(1)-C(2) and N(1)-C(7a) bond formation, respectively, in a two-step one-pot procedure.",10.1021/jo501114a,2014-07-29,0.581176231511196
Synthesis,Enantioconvergent Route to a Functionalized Quinane System,"All articles of this category Enantioconvergent route to both enantiomers of a functionalized quinane, methyl 6-oxo- cis -bicyclo[3.3.0]oct-7-ene-3- endo -carboxylate, has been developed by employing lipase-mediated resolution and Wharton rearrangement.",10.1055/s-1994-25630,1994-01-01,0.5811677627754414
Organic Letters,Toward Leiodermatolide: Synthesis of the Core Structure,"The macrocyclic core (35) of the marine natural product leiodermatolide (1) was synthesized from two key fragments, vinyl iodide 23 (C1-C11 part) and vinyl stannane 31 (C12-C18 part). A Stille coupling led to conjugated Z,Z-diene 32. The derived seco acid 34 was cyclized using a Yamaguchi macrolactonization. Key steps in the assembly of vinyl iodide 23 were a Paterson aldol reaction, and a Kumada coupling on a triflate derivative to create the C4-C5 trisubstituted double bond. The two stereocenters in fragment 31 were established by a Marshall-Tamaru reaction. The longest linear sequence comprises 20 steps.",10.1021/acs.orglett.6b01355,2016-06-09,0.5811612514360395
Synthesis,Improved One-Pot Synthesis of 1-Aryl-3-trifluoroacetyl-1H-pyrroles under Swern Oxidation,"This study describes an improved one-pot, four-step synthesis­ of a new series of 1-aryl-3-trifluoroacetyl pyrroles from the reaction of 3-trifluoroacetyl-4,5-dihydrofuran with arylamines, giving 1,1,1-trifluoro-3-(2-hydroxyethyl)-4-arylamino-3-buten-2-ones, which were directly submitted to Swern oxidation to furnish 1,1,1-trifluoro-3-(2-ethanal)-4-arylamino-3-buten-2-ones. Subsequent intramolecular cyclization of the corresponding enaminoaldehydes followed by aromatization rendered the title compounds in a 30 to 56% overall yield.",10.1055/s-0032-1317383,2012-10-02,0.5811601117590073
Journal of Organic Chemistry,A Formal Synthesis of Porantheridine and an Epimer,"A formal synthesis of porantheridine and a synthesis of its C6-epimer have been completed, employing silver-catalyzed allene cyclization to form a common cis-isoxazolidine intermediate and related N-acyl iminium ion intermediates for side-chain introduction. The stereochemistry of this step can be controlled by choice of the N-protection method.",10.1021/jo9021925,2009-11-25,0.5811572518326936
Organic Letters,Sulfonimidates: Useful Synthetic Intermediates for Sulfoximine Synthesis via C–S Bond Formation,Medicinally relevant sulfoximines are accessed from C-S coupling of sulfonimidates and commercially available organomagnesium reagents. Sulfonimidates are conveniently synthesized by oxidative alkoxylation of readily available sulfinamides. This constitutes a general C-S coupling approach for the synthesis of sulfoximines.,10.1021/acs.orglett.8b01473,2018-06-07,0.5811489658940621
Journal of Organic Chemistry,Practical Synthesis of <i>trans</i>-<i>tert</i>-Butyl-2-aminocyclopentylcarbamate and Resolution of Enantiomers,Optically active trans-tert-butyl-2-aminocyclopentylcarbamate (1) has potential utility as a scaffold for chiral ligands and as a modified backbone unit for peptide nucleic acids (PNAs). We have developed a short and practical synthesis of 1 via aziridine opening of tosyl-activated cyclopentene aziridine 2 and optical resolution of racemic 1 with 10-camphorsulfonic acid (CSA). The route provides ready access to multigram quantities of both enantiomers without the need for chromatography.,10.1021/jo061409v,2006-10-01,0.5811458213305655
Synthesis,"A New Synthesis of 2,5-Dimethyl-3(2<i>H</i>)-furanone",,10.1055/s-1977-24558,1977-01-01,0.5811445020831307
Synthesis,"A New Synthesis of Dimethyl 4-Arylselenophene-2,3-dicarboxylates",,10.1055/s-1977-24566,1977-01-01,0.5811445020831307
Organic Letters,Short and Efficient Synthesis of a Vinyl-Substituted Tricyclic Erythromycin Derivative,"Tricyclic erythromycin A derivatives are known potent antibacterial agents, but the potential of substituted tricyclic erythromycin A derivatives remains largely unexplored. To study this lead, the tricyclic ring system was synthesized by an efficient three-step synthesis starting from the allylic alcohol utilizing a novel azidoisocyanate. These tricyclic analogues can be used as scaffolds to probe secondary ribosomal binding sites. [structure: see text]",10.1021/ol047406r,2005-02-09,0.581142044854241
Angewandte Chemie International Edition,"Stereocontrolled Synthesis of the Quinaldic Acid Macrocyclic System of Thiostrepton We thank Drs. D. H. Huang and G. Suizdak for NMR spectroscopic and mass spectrometric assistance, respectively, as well as Mike Sertic (University of California, San Diego) for experimental assistance. Financial support for this work was provided by The Skaggs Institute for Chemical Biology, the National Institutes of Health (USA), fellowships from The Skaggs Institute for Research (to M.Z. and F.Z.), and grants from Abbott, Amgen, Array Biopharma, Boehringer-Ingelheim, Glaxo, Hoffmann-LaRoche, DuPont, Merck, Novartis, Pfizer, and Schering Plough.","An efficient construction of the quinaldic acid macrocycle (see picture) of the antibiotic thiostrepton is based on state-of-the-art asymmetric synthesis. The 27-membered macrocycle includes a quinaldic acid moiety, a thiazole ring, and a dehydroalanine unit. The key steps in the convergent assembly included: a) amide bond formation, b) esterification, and c) macrolactamization.",10.1002/1521-3773(20020603)41:11<1937::aid-anie1937>3.0.co;2-y,2002-06-03,0.581136691310722
Journal of Organic Chemistry,"A General Synthetic Entry to the Pentacyclic <i>Strychnos</i> Alkaloid Family, Using a [4 + 2]-Cycloaddition/Rearrangement Cascade Sequence","The total synthesis of (+/-)-strychnopivotine, (+/-)-tubifolidine, (+/-)-strychnine, and (+/-)-valparicine is reported. The central step in the synthesis consists of an intramolecular [4 + 2]-cycloaddition/rearrangement cascade of an indolyl-substituted amidofuran that delivers an aza-tetracyclic substructure containing the ABCE-rings of the Strychnos alkaloid family. A large substituent group on the amide nitrogen atom causes the reactive s- trans conformation of the amidofuran to be more highly populated, thereby facilitating the Diels-Alder cycloaddition. The reaction also requires the presence of an electron-withdrawing substituent on the indole nitrogen for the cycloaddition to proceed. The cycloaddition/rearrangement cascade was remarkably efficient given that two heteroaromatic systems are compromised in the reaction. Closure to the remaining D-ring of the Strychnos skeleton was carried out from the aza-tetracyclic intermediate by an intramolecular palladium-catalyzed enolate-driven cross-coupling between the N-tethered vinyl iodide and the keto functionality. The cycloaddition/rearrangement approach was successfully applied to (+/-)-strychnopivotine (2), the only Strychnos alkaloid bearing a 2-acylindoline moiety in its pentacyclic framework. A variation of this tactic was then utilized for a synthesis of the heptacyclic framework of (+/-)-strychnine. The total synthesis of (+/-)-strychnine required only 13 steps from furanyl indole 18 and proceeded in an overall yield of 4.4%.",10.1021/jo8003716,2008-04-01,0.5811313286281617
Organic Process Research & Development,Palbociclib Commercial Manufacturing Process Development. Part II: Regioselective Heck Coupling with Polymorph Control for Processability,"A three-step commercial manufacturing route has been developed for palbociclib, a highly selective, reversible inhibitor of CDK 4/6. The second step, which utilizes a Heck coupling to install the enol ether side chain, is described. A highly regioselective catalyst was identified for this transformation along with reaction conditions that ensure robustness upon scale-up. Effective removal of palladium was accomplished via filtration of insoluble metal and an extractive chelation step. Finally, efficient isolation of coupled product 3 was achieved through careful polymorph control via seeding and an optimized cooling protocol that avoids nucleation of a kinetically favored, slow-filtering polymorph.",10.1021/acs.oprd.6b00069,2016-05-12,0.581129866106406
Tetrahedron,Synthetic studies on the phorboxazoles: a short synthesis of an epi-C23 tetrahydropyran core,,10.1016/j.tetlet.2010.07.012,2010-07-08,0.5811287764037913
Angewandte Chemie International Edition,Modular Synthesis of Nona‐Decasaccharide Motif from <i>Psidium guajava</i> Polysaccharides: Orthogonal One‐Pot Glycosylation Strategy,"The synthesis of long, branched, and complex carbohydrate sequences remains a challenging task in chemical synthesis. Reported here is an efficient and modular one-pot synthesis of a nona-decasaccharide and shorter sequences from Psidium guajava polysaccharides, which have the potent α-glucosidase inhibitory activity. The synthetic strategy features: 1) several one-pot glycosylation reactions on the basis of N-phenyltrifluoroacetimidate (PTFAI) and Yu glycosylation to streamline the chemical synthesis of oligosaccharides, 2) the successful and efficient assembly sequences (first O3', second O5', final O2') toward the challenging 2,3,5-branched Araf motif, 3) the stereoselective 1,2-cis-glucosylation by reagent control, and 4) the convergent [6+6+7] one-pot coupling reaction for the final assembly of the target nona-decasaccharide. This orthogonal one-pot glycosylation strategy can streamline the chemical synthesis of long, branched, and complicated carbohydrate chains.",10.1002/anie.202000992,2020-02-22,0.5811205076342769
Tetrahedron,Enantioselective synthesis of the carbocyclic moiety of (−)-carbovir,,10.1016/s0040-4039(03)00749-4,2003-05-01,0.5811205059478027
Journal of Organic Chemistry,Total Synthesis of Ustiloxin D Utilizing an Ammonia–Ugi Reaction,"Total synthesis of the highly functionalized cyclic peptide natural product, ustiloxin D, has been achieved in a convergent manner. Our strategy incorporates an asymmetric allylic alkylation to construct the tert-alkyl aryl ether linkage between the dopa and isoleucine residues. The elaborated β-hydroxydopa derivative is rapidly converted to a linear tripeptide through an ammonia-Ugi reaction. Subsequent cyclization and global deprotection affords ustiloxin D in six steps from a known β-hydroxydopa derivative.",10.1021/acs.joc.5b01519,2015-09-22,0.5811075187074809
Journal of Organic Chemistry,Synthesis of (±)-Aphanorphine Using Rh-Catalyzed Cyclohydrocarbonylation,"A facile formal synthesis to aphanorphine and its analogue is described, featuring Rh-catalyzed cyclohydrocarbonylation of 2-aminodihydronaphthalene to the bridged benzazepine core. Subsequent introduction of the methyl group and functional group transformation complete the synthesis of aphanorphine and its analogue over eight steps.",10.1021/acs.joc.7b00923,2017-07-10,0.5811026696581638
Angewandte Chemie International Edition,The Winding Pathway to Erythropoietin Along the Chemistry–Biology Frontier: A Success At Last,"The total synthesis of a homogeneous erythropoietin (EPO), possessing the native amino acid sequence and chitobiose glycans at each of the three wild-type sites of N glycosylation, has been accomplished in our laboratory. We provide herein an account of our decade-long research effort en route to this formidable target compound. The optimization of the synergy of the two bedrock sciences we now call biology and chemistry was central to the success of the synthesis of EPO.",10.1002/anie.201301666,2013-06-17,0.5810939326504578
Tetrahedron,Studies in macrolide synthesis: a synthesis of two chiral fragments of oleandomycin and lankamycin.,,10.1016/s0040-4039(00)81643-3,1983-01-01,0.5810931045315643
Synlett,"An Alkene-Forming Cascade Reaction En Route to 2,2'-Bi(glycerol)","Synthesis of 2,3-bis(hydroxymethyl)butane-1,2,3,4-tetraol is of great interest because of its utility as a potential precursor to new dendrimers, in the preparation of unnatural lipids, and in the synthesis of open-framework coordination polymers. Synthesis of this new six-­hydroxyl compound is achieved in four steps from commercially available starting materials. In this process, a new olefin-forming cascade ­reaction was discovered.",10.1055/s-0037-1610037,2018-06-12,0.5810906700148315
Journal of Organic Chemistry,A Total Synthesis of Hydroxylysine in Protected Form and Investigations of the Reductive Opening of <i>p</i>-Methoxybenzylidene Acetals,"A synthesis of (2S,5R)-5-hydoxylysine, based on (R)-malic acid and Williams glycine template as chiral precursors, has been developed. This afforded hydroxylysine, suitably protected for direct use in peptide synthesis, in 32% yield over the 13-step sequence. Regioselective reductive opening of a p-methoxybenzylidene acetal and alkylation of the Williams glycine template were key steps in the synthetic sequence. Surprisingly, the regioselectivity in opening of the p-methoxybenzylidene acetal was reversed as compared to what was expected. It was found that this was due to chelation of the trialkylsilyl choride, used as an electrophile in the reductive opening, to an adjacent azide functionality. It was also discovered that an equivalent amount of trialkylsilyl hydride was formed in the reaction, a finding that led to additional mechanistic insight into reductive openings of p-methoxybenzylidene acetals with sodium cyanoborohydride as reducing agent.",10.1021/jo049136w,2004-11-12,0.5810862973599246
Organic Letters,Biomimetic Synthesis Enables the Structure Revision of Furoerioaustralasine,"The structure of furoerioaustralasine, a unique Australian alkaloid, has been revised based on a concise, biomimetic synthesis. The key step is a stereospecific, intramolecular ring opening of an epoxide to form a central dihydrofuran fused to a quinoline ring system.",10.1021/acs.orglett.9b03392,2019-10-11,0.5810860370629475
Tetrahedron,"Synthesis of a new fluorinated analog of (E,E)-8,10 dodecadienol (codlemone)",,10.1016/s0040-4039(00)92524-3,1992-06-01,0.5810830941353851
Tetrahedron,"Synthesis of estra-1,3,5(10)-trien-3,15α,16α,17β-tetrol a new metabolite of estradiol",,10.1016/s0040-4039(00)90889-x,1967-01-01,0.5810830941353851
Journal of Organic Chemistry,Diastereoselective Dihydroxylation and Regioselective Deoxygenation of Dihydropyranones:  A Novel Protocol for the Stereoselective Synthesis of C<sub>1</sub>−C<sub>8</sub> and C<sub>15</sub>−C<sub>21</sub> Subunits of (+)-Discodermolide,"Diastereoselective dihydroxylation of dihydropyranones and subsequent regioselective alpha-deoxygenation provides 1,3-trans-beta-hydroxy-delta-lactones stereoselectively. This protocol has been applied for the synthesis of C(1)-C(8) and C(15)-C(21) subunits of (+)-discodermolide.",10.1021/jo0492416,2004-08-05,0.5810770116258144
Organic Letters,Amination/Cyclization Cascade by Acid-Catalyzed Activation of Indolenine for the One-Pot Synthesis of Phaitanthrin E,"We have developed a concise one-pot synthesis of phaitanthrin E derivatives, where simple starting materials undergo an acid-catalyzed intermolecular amination/intramolecular cyclization cascade.",10.1021/acs.orglett.6b03466,2016-12-02,0.5810751299855318
Journal of Organic Chemistry,Total Synthesis of (<i>R</i>)-Sarkomycin via Asymmetric Rhodium-Catalyzed Conjugate Addition,"(R)-Sarkomycin was prepared using a five-step total synthesis. Key steps in the enantioselective construction of the targeted scaffold were a rhodium-catalyzed asymmetric conjugate alkenyl addition with subsequent silyl trapping and a Mukaiyama aldol reaction with aqueous formaldehyde. Protection of the hydroxy group as a THP acetal and oxidative cleavage of the C,C-double bond provided a stable direct precursor to the natural product. The final liberation was carried out under slightly acidic conditions in a microwave-assisted reaction, resulting in a high yield of the ""deceptive"" sarkomycin. This represents the shortest enantioselective synthesis of this rather unstable compound to date and the first to employ asymmetric catalysis to introduce the stereogenic center.",10.1021/jo4016979,2013-09-30,0.5810709508401349
Journal of Organic Chemistry,Synthesis of Cyclopropene Analogues of Ceramide and Their Effect on Dihydroceramide Desaturase,"The synthesis of several analogues of the N-[(1R,2S)-2-hydroxy-1-hydroxymethyl-2-(2-tridecyl-1-cyclopropenyl)ethyl]octanamide (GT11), the first reported inhibitor of dihydroceramide desaturase, as well as their effects on this enzyme, are described. Modifications of the parent structure include variations on the cyclopropene ring, the N-acyl chain length, the configuration of the stereocenters, and the hydroxyl group at C1. The key intermediates for the synthesis are the products resulting from the addition of suitable organolithium compounds to either Garner's aldehyde or its enantiomer. The final products are obtained by TMSTf-induced cleavage of the protecting groups and N-acylation, both under specific conditions. An alternative method for N-Boc deprotection is also reported that allows us to obtain the cyclopropene analogue of sphingosine 12a, which can be transformed into GT11 upon acylation. The procedure consists of the conversion of the Garner aldehyde addition products into the bicyclic dihydrooxazolo[3,4,0]oxazol-3-ones 19 by transesterification in basic medium of the tert-butyl group with the hydroxyl function at C3. Mild cleavage of the N,O-isopropylidene cyclic acetal present in 19 affords the oxazolidin-2-one 20, which gives 12a upon saponification. Furthermore, compound 20 is also the key intermediate in the synthesis of the terminal deoxy, methoxy, and fluoro derivatives 9, 10, and 11, respectively. Determination of dihydroceramide desaturase activity in vitro showed that GT11 was a competitive inhibitor (Ki = 6 microM) and that its analogues with N-hexanoyl (6) and N-decanoyl (7) moieties inhibited the enzyme with similar potencies (IC50 = 13 and 31 microM, respectively). No decrease in dihydroceramide desaturase activity was observed with any of the other compounds tested.",10.1021/jo030141u,2003-12-01,0.5810637197381359
Tetrahedron,Ring opening reactions of thiiranes with group IV B organometallics: a new regioselective route to β-amino and β-cyanide thiols.,,10.1016/s0040-4039(00)81911-5,1983-01-01,0.5810601328137692
Angewandte Chemie International Edition,A Short Total Synthesis of the Marine Sponge Pyrrole‐2‐aminoimidazole Alkaloid (±)‐Agelastatin A,Ring by ring: (±)-Agelastatin A has been synthesized through the use of domino and one-pot reactions while minimizing protecting group usage. The core was accessed through a stereoselective domino condensation/ring-opening/4π-conrotatory electrocyclization and elaborated using newly developed protocols for urea and amide formation. Oxidation of an unprotected pre-agelastatin A and an intramolecular aza-Michael reaction completed the synthesis in only six steps.,10.1002/anie.201304759,2013-08-22,0.5810594864276616
Tetrahedron,"Novel C-nucleoside analogs of 1,3-dioxolane: Synthesis of enantiomeric (2′R,4′S)- and (2′S,4′R)-2-[4-(hydroxymethyl)-1,3-dioxolan-2-yl]-1,3-thiazol-4-carboxamide",,10.1016/0040-4039(95)00625-m,1995-05-01,0.5810584313254886
Angewandte Chemie International Edition,"Iridium‐Catalyzed Asymmetric Hydrogenation of Benzo[<i>b</i>]thiophene 1,1‐Dioxides","An efficient iridium-catalyzed asymmetric hydrogenation of substituted benzothiophene 1,1-dioxides is described. The use of iridium complexes with chiral pyridyl phosphinite ligands provides access to highly enantiomerically enriched sulfones with substituents at the 2- and 3-position. Sulfones of this type are of interest as core structures of agrochemicals and pharmaceuticals. Moreover, they can be further reduced to chiral 2,3-dihydrobenzothiophenes.",10.1002/anie.201701409,2017-03-23,0.581056213710604
Journal of Organic Chemistry,"Unified Total Syntheses of Anticancer Agent Nepetaefolin F and Indolosesquiterpenoids, Oridamycins A and B","The asymmetric total syntheses of triptobenzene L ( 1a ), 4- epi -triptobenzene L ( 1c ), nepetaefolin F ( 1b ), and oridamycins A ( 2c ) and B methyl ester ( 2a ) have been accomplished through an enantioselective divergent approach from a highly functionalized common intermediate. A Lewis-acid-mediated highly regio- and diastereoselective epoxy-ene cyclization of (−)- 6 [92% ee] afforded the highly functionalized carbotricyclic core (+)- 5 [82%, dr >20:1] sharing four contiguous stereogenic centers [out of which two are all-carbon quaternary stereogenic centers]. Efficient functionalization of the advanced intermediate enabled the successful asymmetric total syntheses of naturally occurring anti -cancer abietane diterpenoid, such as 1b and indolosesquiterpenoids 2a and 2c .",10.1021/acs.joc.5c00179,2025-03-30,0.5810539143743777
Tetrahedron,A short and efficient synthesis of (−)-Ambrox® from (−)-sclareol using a ruthenium oxide catalyzed key step.,,10.1016/s0040-4039(00)61637-4,1993-01-01,0.5810503435977795
Organic Letters,Improved Synthesis of <i>tert</i>-Butanesulfinamide Suitable for Large-Scale Production,[reaction: see text] An improved synthesis of tert-butanesulfinamide that overcomes the scalability problems of the previous syntheses is described. The key step is the catalytic asymmetric oxidation of the inexpensive di-tert-butyl disulfide starting material. The new homogeneous reaction conditions utilize an inexpensive chiral ligand prepared in a single step from commercially available cis-1-amino-indan-2-ol. The reaction is performed at a 2.3 M concentration in the practical solvent acetone and can readily be run on a kilogram scale.,10.1021/ol034254b,2003-03-15,0.5810483349403175
Synthesis,An Expeditious Enantiospecific Total Synthesis of (-)-Crassalactone C,A concise and expeditious approach for the total synthesis of bioactive styryllactone (–)-crassalactone C is presented from tartaric acid. The main features of the synthesis include the desymmetrization of dimethylamide of tartaric acid and the effective use of cinnamoyl ester as a protecting group as well as a reactant in the ring-closing metathesis reaction.,10.1055/s-0032-1318303,2013-02-21,0.5810431149202101
Tetrahedron,Nickel- and palladium-catalyzed cross-coupling as a route to 1- and 2-alkoxy- or dialkylaminovinylphosphonates,,10.1016/s0040-4039(98)02358-2,1999-01-01,0.581037710151481
Tetrahedron,Total synthesis of E1 and E2 isoprostanes by diastereoselective protonation,,10.1016/s0040-4039(02)02252-9,2002-12-01,0.581037433418838
Tetrahedron,Diastereoselective total synthesis of 8-epigrosheimin,,10.1016/j.tetlet.2008.12.025,2008-12-14,0.581037433418838
Tetrahedron,A novel synthetic approach to N-unsubstituted β-lactams,,10.1016/s0040-4039(00)99001-4,1985-01-01,0.5810363955933533
Tetrahedron,A novel synthetic approach to α-alkylidene-α-lactams,,10.1016/s0040-4039(00)97398-2,1990-01-01,0.5810363955933533
Tetrahedron,A novel synthetic approach to angularly fused tricyclopentanoids,,10.1016/s0040-4039(01)91053-6,1984-01-01,0.5810363955933533
Tetrahedron,A novel synthetic approach towards 2-guanidinomethyl-4(5)-sulfamoylimidazoles,,10.1016/j.tetlet.2004.05.143,2004-06-25,0.5810363955933533
Angewandte Chemie International Edition,"Nickel‐Catalyzed Enantioselective Reductive Cyclization of 1,3‐Dienes Toward α‐Chiral Six‐Membered Silacycles","Chiral organosilanes are increasingly important in synthetic, medicinal, and materials chemistry. However, the enantioselective synthesis of α-chiral six-membered silacycles remains unexplored. Here, we report two nickel-catalyzed enantioselective reductive [4 + 2] cyclizations of 1,3-dienes using readily available chloromethyl chlorosilane or 1,2-dichlorodisilane as dielectrophiles, proceeding via distinct mechanisms. Our strategy represents the first reductive cyclization involving both C-Si bond and C-C bond formation and enables efficient and highly enantioselective access to α-chiral silacyclohexenes and 1,2-disilacyclohexenes with broad functional group compatibility. Further derivatizations demonstrate the potential of this method for constructing valuable chiral silicon building blocks, underscoring its synthetic utility.",10.1002/anie.202515185,2025-11-10,0.5810309343487559
Angewandte Chemie International Edition,"Total Synthesis of Everninomicin 13,384-1—Part 1: Synthesis of the A1B(A)C Fragment","The powerful antibiotic everninomicin 13,384-1 (1, Ziracin) has been prepared for the first time through a total synthesis. The 1→1′-disaccharide and the two orthoesters of this target molecule were introduced by new methodologies using a tin acetal and 1,2-phenylseleno migrations. The reaction sequence also relies on stereoselective glycosidations and subtle manipulations of protecting groups. In addition to the introduction of new synthetic methodologies, this total synthesis should allow the preparation of combinatorial libraries of semisynthetic analogues of this highly promising antibiotic for biological screening purposes.",10.1002/(sici)1521-3773(19991115)38:22<3334::aid-anie3334>3.3.co;2-8,1999-11-15,0.5810251350855241
Angewandte Chemie International Edition,"Total Synthesis of Everninomicin 13,384-1—Part 2: Synthesis of the FGHA2 Fragment","The powerful antibiotic everninomicin 13,384-1 (1, Ziracin) has been prepared for the first time through a total synthesis. The 1-->1'-disaccharide and the two orthoesters of this target molecule were introduced by new methodologies using a tin acetal and 1,2-phenylseleno migrations. The reaction sequence also relies on stereoselective glycosidations and subtle manipulations of protecting groups. In addition to the introduction of new synthetic methodologies, this total synthesis should allow the preparation of combinatorial libraries of semisynthetic analogues of this highly promising antibiotic for biological screening purposes.",10.1002/(sici)1521-3773(19991115)38:22<3340::aid-anie3340>3.0.co;2-2,1999-11-15,0.5810251350855241
Angewandte Chemie International Edition,"Total Synthesis of Everninomicin 13,384-1—Part 1: Synthesis of the A1B(A)C Fragment","The powerful antibiotic everninomicin 13,384-1 (1, Ziracin) has been prepared for the first time through a total synthesis. The 1→1′-disaccharide and the two orthoesters of this target molecule were introduced by new methodologies using a tin acetal and 1,2-phenylseleno migrations. The reaction sequence also relies on stereoselective glycosidations and subtle manipulations of protecting groups. In addition to the introduction of new synthetic methodologies, this total synthesis should allow the preparation of combinatorial libraries of semisynthetic analogues of this highly promising antibiotic for biological screening purposes.",10.1002/(sici)1521-3773(19991115)38:22<3334::aid-anie3334>3.0.co;2-h,1999-11-15,0.5810251350855241
Journal of Organic Chemistry,"Synthesis of an Azido Precursor to (2<i>S</i>,5<i>R</i>)-5-Hydroxylysine Using an Asymmetric Organocatalytic Chlorination/Reduction Sequence","An efficient, robust, and scalable synthesis of an azido precursor to the modified amino acid (2S,5R)-5-hydroxylysine was developed on the basis of the use of a highly stereoselective organocatalytic α-chlorination-reduction protocol. The final Fmoc-protected (2S,5R)-6-azido-5-hydroxylysine derivative can be used in solid-phase peptide synthesis, providing access to proteins that contain large quantities of post-translationally modified lysine (e.g., collagens).",10.1021/jo402220s,2013-10-31,0.5810232056861976
Synlett,Synthesis of Boronocysteine,"Herein we report the first synthesis of protected boronocysteine. The target compound was prepared via copper-catalysed diastereoselective nucleophilic borylation of a sulfinimine. After deprotection to give the amine as the hydrochloride salt, four boronocysteine amide derivatives were prepared through reaction with a variety of different active acylating agents.",10.1055/s-0036-1591491,2017-10-20,0.5810215994355866
Synlett,A Simple and Practical Synthesis of 1-β-Methylcarbapenems Based on the Counterattack Strategy,All articles of this category A convenient synthesis of 1-β-methylcarbapenems from thioesters via chlorotrimethylsilane mediated Dieckmann-type cyclization followed by counterattack of thiolate anion is described. 1-β-methylcarbapenem - counterattack reagent - Dieckmann-type cyclization,10.1055/s-1995-4969,1995-04-01,0.5810214997088107
Tetrahedron,"Synthesis of 7,8-acetylenic analogs of hexahydro leukotriene-E4 with agonist and antagonist activities: convenient stereoselective routes to E- and Z-enynes",,10.1016/s0040-4039(00)99017-8,1985-01-01,0.5810210218324664
Tetrahedron,A synthetic study of magallanesine by cyclization of a benzamidoacrylate intermediate,,10.1016/j.tetlet.2015.04.085,2015-05-05,0.5810164299139383
Journal of the American Chemical Society,Enantioselective Photocycloaddition Mediated by Chiral Brønsted Acids:  Asymmetric Synthesis of the Rocaglamides,Enantioselective syntheses of methyl rocaglate and the related natural products rocaglamide and rocaglaol are outlined. The approach involves enantioselective [3 + 2] photocycloaddition promoted by chiral Brønsted acids (TADDOLs) to afford an aglain precursor followed by a ketol shift/reduction sequence to the rocaglate core.,10.1021/ja062621j,2006-05-25,0.5810158111912112
Organic Letters,"B(C <sub>6</sub> F <sub>5</sub> ) <sub>3</sub> -Catalyzed (5 + 1)-Annulation of Enynamides with Trihydrosilanes en Route to the Synthesis of 1,4-Azasilines","Silaazacycles are emerging as promising heavier bioisosteres of N-heterocycles in drug discovery. Among them, 1,4-azasiline, a versatile scaffold that enables access to diverse silaazacycles, has remained underexplored, largely due to the lack of efficient synthetic methods. Here we report a B(C 6 F 5 ) 3 -catalyzed (5 + 1)-annulation of enynamides and trihydrosilanes, providing direct access to 1,4-azasilines and benzo-fused 1,4-azasilines. Mechanistic studies suggest that the reaction begins with a chemoselective and regioselective β-hydrosilylation of the enamide moiety, which exhibits higher reactivity than the ynamide unit within the enynamide substrate.",10.1021/acs.orglett.5c04900,2025-12-31,0.5810050243017084
Synlett,"Convenient Asymmetric Synthesis of (1<i>R</i>,3<i>R</i>)-(+)- and (1<i>S</i>,3<i>S</i>)-(-)-1,3-Diphenylpropane-1,3-diols","All articles of this category Kinetic resolution via a Sharpless epoxidation serves as the key step to provide the useful C 2 chiral auxiliaries ( R,R )- and ( S,S )-1,3-diphenylpropane-1,3-diols, in good yield and high enantiomeric purity from the commercially available 1,3-diphenylprop-1-en-3-one. Sharpless epoxidation - Kinetic resolution - Asymmetric synthesis - C 2 symmetric 1,3-diols - 1,3-Diphenylpropan-1,3-diols",10.1055/s-1996-5703,1996-12-01,0.5810025218255543
Journal of Organic Chemistry,"Total Synthesis of the Proposed Structure of 8-Deshydroxyajudazol A: A Modified Approach to 2,4-Disubstituted Oxazoles","The total synthesis of the proposed structure for the minor myxobacterial metabolite 8-deshydroxyajudazol A (3) is described. The isochromanone moiety present in the eastern fragment was constructed by an intramolecular-Diels-Alder (IMDA). Difficulties were encountered with the formation of the 2,4-disubstituted oxazole, so this was synthesized via a modified approach. This involved selective acylation of the diol 7 with acid 8, azide displacement of the secondary alcohol, and subsequent azide reduction in the presence of base which induced an O,N shift to give the hydroxyamide 23. Cyclodehydration then gave the desired oxazole 24 and deprotection followed by mesylation and elimination produced the C15 alkene 5. Sonogashira coupling with the eastern fragment vinyl iodide 6 and partial reduction yielded 8-deshydroxyajudazol A (3).",10.1021/jo302055w,2012-11-06,0.5809944160405001
Journal of Organic Chemistry,"Chemoenzymatic Synthesis of <scp>d</scp>-<i>N</i>-Boc-3,5- dihydroxy-4-methoxyphenylglycine","The authors describe an efficient synthesis of nonproteinogenic title amino acid I, an important building block in the synthesis of vancomycin-type antibiotics. The chirality was introduced by AMANO acylase-catalyzed enantioselective hydrolysis, and the overall yield of I was 36% starting from 3,5-bis(isopropoxy)-4-methoxybenzaldehyde. The efficiency of both protease- and acylase-catalyzed hydrolysis reactions depends significantly on the protecting groups used for the two phenoxy functions on the arom. ring. Besides the steric reason, the beneficial effect of the free hydroxy groups in compd. II may be attributed to hydrogen bonding donor properties as well as possible dipole-dipole interactions in the binding region of the enzyme. To the best of the author's knowledge, this the first time that the trifluoroacetyl group has been used as the acyl group in aminoacylase-catalyzed hydrolysis of amides, the main advantages being its easy prepn. and mild chem. hydrolysis. This synthetic route is amenable to the synthesis of I on a multigram scale. [on SciFinder (R)]",10.1021/jo980233x,1998-07-17,0.5809902684040592
Synthesis,Chiral Sulfoxides in Asymmetric Synthesis: A New Chiral Synthesis of Optically Active 4-Substituted Cyclohexylideneacetic Acid Esters,,10.1055/s-1985-31299,1985-01-01,0.5809878985713155
European Journal of Organic Chemistry,"A Ring Expansion Route to Benzofused N‐Heterocycles Through Aryne Insertion into 1,3‐Diaza‐heterocycles","Arynes have been found to undergo formal σ‐bond insertion into a C(sp3)–N bond for the first time. This transformation is utilized in the ring expansion of 1,3‐diaza‐heterocycles to afford benzofused medium‐ring N‐heterocycles in a single step. This represents a novel route to biologically relevant 2,3,4,5‐tetrahydro‐1 H ‐benzo[ e ][1,4]diazepines, prepared directly from easily accessible imidazolidines. An example of the ring expansion of a 1,3‐diazetidine is also reported, which affords the corresponding 1,2,3,4‐tetrahydroquinazoline.",10.1002/ejoc.201900570,2019-05-22,0.5809875734951007
Synthesis,Enantioselective Synthesis of Endocyclic β-Amino Acids with Two Contiguous Stereocenters via Hydrogenation of 3-Alkoxycarbonyl-2-Substituted Quinolines,An enantioselective iridium-catalyzed hydrogenation of 3-alkoxycarbonyl-2-substituted quinoline derivatives is described. This methodology provides a convenient route to enantiopure endocyclic β-amino acids with two contiguous stereocenters with up to 90% ee.,10.1055/s-0033-1339849,2013-09-25,0.5809800803645364
Synlett,Novel <i>C</i><sub>2</sub>-Symmetric Chiral Oxazolinyl Biaryl Ligands Bearing a Hydroxyl Group,"All articles of this category Novel C 2 -symmetric bisoxazoline ligands 4 and 5 having an axis-fixed and -unfixed biaryl backbone, respectively, and a hydroxyl group in the substituent of the oxazoline ring, were prepared from biaryl dicarboxylic acids and l-serine methyl ester hydrochloride through the corresponding bisoxazolines 7 and the biphenyl derivative bearing a methoxycarbonyl substituent as the intermediate. With these ligands, up to 88% ee was afforded for the asymmetric alkylation of benzaldehyde with diethylzinc. multi-chirality - oxazoline - axial chirality - asymmetric alkylation - diethyl zinc",10.1055/s-2000-6510,2000-02-01,0.5809706966830926
Organic Letters,Synthesis of the Spirotetracyclic Core of the Ginkgolides via a Malonyl Radical Cascade,"High Resolution Image Download MS PowerPoint Slide The ginkgolides are a family of terpene trilactone natural products exclusive to the Ginkgo biloba tree. Here, we present a concise synthesis of their spirotetracyclic core via a manganese(III)-mediated oxidative radical cascade. Beginning from six simple starting materials, this route enables the diastereoselective synthesis of rings A, B, D and E of the natural product in nine steps, laying the foundations for their total synthesis.",10.1021/acs.orglett.5c02247,2025-07-14,0.5809700211001718
Organic Letters,A Mild and Efficient One-Step Synthesis of Quinolines,"[reaction: see text] The Friedländer synthesis of quinolines is an extensively employed protocol, yielding the desired heterocycle in a two-step reduction-condensation sequence. We have developed a mild, efficient, high-yielding single-step variant of this methodology, which employs SnCl(2) and ZnCl(2) to effect the reaction.",10.1021/ol035333q,2003-10-21,0.580969873042119
Journal of the American Chemical Society,Asymmetric Nitrone Synthesis via Ligand-Enabled Copper-Catalyzed Cope-Type Hydroamination of Cyclopropene with Oxime,"We report realization of the first enantioselective Cope-type hydroamination of oximes for asymmetric nitrone synthesis. The ligand promoted asymmetric cyclopropene “hydronitronylation” process employs a Cu-based catalytic system and readily available starting materials, operates under mild conditions and displays broad scope and exceptionally high enantio- and diastereocontrol. Preliminary mechanistic studies corroborate a Cu I -catalytic profile featuring an olefin metalla -retro-Cope aminocupration process as the key C–N bond forming event. This conceptually novel reactivity enables the first example of highly enantioselective catalytic nitrone formation process and will likely spur further developments that may significantly expedite chiral nitrone synthesis.",10.1021/jacs.7b06523,2017-08-07,0.5809616831898616
Synthesis,"Trimethylsilyl Iodide as a Multifunctional Agent in the One-Pot Synthesis of 9-(1H-Indol-3-yl)xanthen-4-(9H)-ones from O-Methyl Protected Salicylaldehydes, Indoles, and β-Dicarbonyl Compounds","Trimethylsilyl iodide (TMSI) is introduced as an efficient reagent for the one-pot synthesis of 9-(1 H -indol-3-yl)xanthen-4-(9 H )-ones using the reaction of 2-methoxybenzaldehydes (as O -methyl protected salicylaldehydes), indoles, and β-dicarbonyl compounds. In this protocol, a set of TMSI reactions involving silylation, silyl enol ether formation, methyl deprotection, and nucleophilic substitution/cyclization are performed to furnish the target product. The key step in this protocol is the deprotection of the methoxy group by TMSI.",10.1055/s-0033-1338633,2014-05-14,0.5809610092756455
Synthesis,"A Novel Synthesis of Thiazolo[2,3-<i>a</i>]pyridine Derivatives",,10.1055/s-1981-29554,1981-01-01,0.5809603994536093
Tetrahedron,Trichloroisocyanuric acid: an efficient reagent for the synthesis of dialkyl chlorophosphates from dialkyl phosphites,,10.1016/j.tetlet.2005.06.024,2005-06-30,0.580959144449036
Organic Letters,"Two-Step Synthesis of 2,3-Dihydropyrroles via a Formal 5-<i>endo</i> Cycloisomerization of Ugi 4-CR/Propargyl Adducts","A practical two-step synthesis of 2,3-dihydropyrroles from Ugi 4-CR/propargyl adducts is presented. The protocol includes a base-mediated formation of an allenamide functional group and an in situ metal-free formal 5-endo cycloisomerization that occurs in a highly regioselective manner at the allenamide C-γ.",10.1021/ol3024727,2012-10-25,0.5809540033697672
Synlett,Total Synthesis of Avermectin B1a: Synthesis of the C11-C25 Spiroacetal Fragment,"All articles of this category During the synthesis of avermectin B1a ( 1 ) the C11-C25 spiroacetal portion 2 has been prepared using a novel sequence of reactions involving π-allyltricarbonyliron lactone complexes 5 and 6 for the preparation of the cyclic ether sulphone, 8 which in turn was coupled and spirocyclised to give 2 .",10.1055/s-1990-21079,1990-01-01,0.5809533947832859
Tetrahedron,Intramolecular cyclization of a dieno-nitrile: synthesis of a new monoterpene alkaloid,,10.1016/s0040-4039(01)96645-6,1971-01-01,0.5809479413293132
Journal of Organic Chemistry,Six-Step Syntheses of (−)-1-Deoxyaltronojirimycin and (+)-1-Deoxymannonojirimycin from <i>N</i>-<i>Z</i>-<i>O</i>-TBDPS-<scp>l</scp>-serinal,Highly stereoselective six-step syntheses of (-)-1-deoxyaltronojirimycin (altro-DNJ) and (+)-1-deoxymannojirimycin (manno-DNJ) from N-Cbz-O-TBDPS-l-serinal are described. Key transformations involve a two-step preparation of a functionalized dihydropyridin-3-one as a common intermediate followed by Luche reduction and dihydroxylation (for altro-DNJ). The same sequence employing an epoxidation/epoxide opening in place of dihydroxylation furnishes manno-DNJ.,10.1021/acs.joc.6b01575,2016-08-08,0.5809405801780978
Journal of Organic Chemistry,Swift and Efficient Synthesis of 4-Phenylquinazolines: Involvement of <i>N</i>-Heterocyclic Carbene in the Key Cyclization Step,"An original route to 2-alkyamino-4-phenylquinazolines in three steps from simple (hetero)aromatic amines is reported here. The key step involves the intramolecular cyclization of benzoyl arylguanidines performed in [OMIm]Cl ionic liquid. The basic (hetero)aromatic guanidines deprotonate the imidazolium-based ionic liquid, thus triggering the cascade process ultimately leading to the intramolecular cyclization. This reaction is the first example of a Friedel-Crafts-type reaction in which an N-heterocyclic carbene is involved in the formation of the electrophilic intermediate.",10.1021/jo902726k,2010-02-19,0.5809405102029837
Angewandte Chemie International Edition,7‐Step Flow Synthesis of the HIV Integrase Inhibitor Dolutegravir,"Dolutegravir (DTG), an important active pharmaceutical ingredient (API) used in combination therapy for the treatment of HIV, has been synthesized in continuous flow. By adapting the reported GlaxoSmithKline process chemistry batch route for Cabotegravir, DTG was produced in 4.5 h in sequential flow operations from commercially available materials. Key features of the synthesis include rapid manufacturing time for pyridone formation, one-step direct amidation of a functionalized pyridone, and telescoping of multiple steps to avoid isolation of intermediates and enable for greater throughput.",10.1002/anie.201802256,2018-05-14,0.5809311102657891
Tetrahedron,Palladium-catalyzed asymmetric synthesis of axially dissymmetric 4-t-butyl-alkylidenecyclohexane derivative,,10.1016/0040-4039(88)85057-3,1988-01-01,0.5809308930832338
Journal of Organic Chemistry,"Enantiospecific Total Synthesis of <scp>l</scp>-2‘,3‘-Dideoxyisonucleosides via Regioselective Opening of Optically Active <i>C</i><sub>2</sub>-Symmetric 1,4-Pentadiene Bis-epoxide<sup>1</sup>","A new method for the synthesis of l -2‘,3‘-dideoxyisonucleosides is described. The readily available, optically active C 2 -symmetric bis-epoxide (2 S,4 S )-1,2:4,5-diepoxypentane ( 5 ) was prepared by a short route from readily available starting materials. The key step of the new synthesis is the opening of 5 with nucleophiles, which proceeds highly regioselectively; e.g., reaction with sodium sulfide affords a 5:1 mixture of the tetrahydrothiophenediol 9a and the tetrahydrothiopyrandiol 14, and reaction with sodium hydroxide gives exclusively the tetrahydrofurandiol 9b via a preferred 5-exo cyclization. These five-membered diols 9a, b can be converted in only four steps into the modified dideoxyuridine and adenosine isonucleosides 4a − c, one of which ( 4c ) has shown good antiviral activity. In addition, we have examined the opening of the analogous six-carbon bis-epoxide, (2 S,5 S )-1,2:5,6-diepoxyhexane ( 23 ), which affords a 3:1 mixture of the hexahydrothiepinediol 24 and the tetrahydrothiopyrandiol 25 with sodium sulfide via a preferred 7-endo cyclization. An alternate route to these two optically active bis-epoxides 5 and 23 was also examined, namely the asymmetric dihydroxylation of 1,4-pentadiene and 1,5-hexadiene followed by selective sulfonylation and epoxide formation. The asymmetric reaction produces a nearly 1:1 mixture of optically active and meso tetrols, e.g., 28 − 9 and 32 − 3 . Unfortunately, the tetrols, their simple derivatives, and the final sulfonates and epoxides could not be readily separated by any simple means.",10.1021/jo9721655,1998-04-02,0.5809287869824861
Journal of Organic Chemistry,Synthesis of the Acyclic Carbon Skeleton of Filipin III,"The synthesis of the carbon skeleton of filipin III, a polyenic macrolactone possessing 11 stereogenic centers, was achieved using a convergent strategy with the longest linear sequence of 19 steps starting from hexanal. Construction of the polyene was realized using two successive Heck couplings as the key steps. Control of the stereogenic centers of the polyol fragment was performed by utilizing an Evans aldolization, a 1,3-syn aldolization, enantio- and diastereoselective allylations, a hemiacetalization/oxa-Michael sequence, and a 1,3-syn reduction. The polyol and polyenic fragments were coupled using a 1,5-anti diastereoselective aldolization followed by a 1,3-anti reduction.",10.1021/acs.joc.6b01166,2016-08-09,0.5809225984585951
Journal of the American Chemical Society,Asymmetric Total Syntheses of Cephalotane-Type Diterpenoids Cephanolides A–D,"Cephanolides A–D are cephalotane-type diterpenoids featuring a novel 6/6/6/5 tetracyclic core embedded with a bridged δ-lactone. The asymmetric and divergent total syntheses of cephanolides A–D have been accomplished, proceeding in 11–14 steps from a known alcohol. The salient features of the present work include (i) a substrate-controlled diastereoselective intermolecular Diels–Alder reaction to form the 6–6 cis -fused rings, (ii) a palladium-catalyzed formal bimolecular [2 + 2 + 2] cycloaddition reaction via a partially intermolecular cascade reaction sequence involving multiple carbometalations to rapidly install the key tetracyclic skeleton, and (iii) lactonization and late-stage oxidative diversification to complete total syntheses of the four benzenoid cephanolides.",10.1021/jacs.2c03978,2022-06-02,0.5809219273160405
Tetrahedron,"Highly stereocontrolled synthesis of fluorinated 2,6-trans dihydropyrans via Prins cyclization",,10.1016/j.tetlet.2009.12.068,2009-12-23,0.5809170430433744
Synthesis,"Synthesis of 2-(4-Fluorophenyl)-4-isopropyl-3-quinolinecarbaldehyde: A New Route to 2,3,4-Substituted Quinolines","All articles of this category A new method for the preparation of 2,3,4-substituted quinolines has been developed and its application towards the synthesis of 2-(4-fluorophenyl)-4-isopropyl-3-quinolinecarbaldehyde, as well as other quinolines, is described.",10.1055/s-1991-26379,1991-01-01,0.5809045489048958
Synthesis,"Improved Synthesis of Anxiolytic, Anticonvulsant, and Antinociceptive α2/α3-GABA(A)-ergic Receptor Subtype Selective Ligands as Promising Agents to Treat Anxiety, Epilepsy, and Neuropathic Pain","An improved synthesis of the anxiolytic, anticonvulsant and antinociceptive compounds: Hz-166, and its bioisosteres 1,2,4-oxadiazole (MP-III-080) and 1,3-oxazole (KRM-II-81) were executed in higher yields and with more facile purification methods (crystallization, etc.) in multigram quantities without column chromatography. In the synthesis of KRM-II-81, an alternative procedure was employed using the selective reducing reagent, potassium diisobutyl-t-butoxy aluminum hydride (PDBBA), to prepare the desired C(3)-aldehyde in the absence of [N(5)-C(6)] imine reduction in good yield on 20 gram scale.",10.1055/s-0037-1610211,2018-07-24,0.5808987243861635
Organic Process Research & Development,Development of a Scalable Process for α-Amino-ω-methoxyl-dodecaethylene Glycol,"We have developed a process for the efficient and scalable preparation of heterofunctionalized dodecaethylene glycol from the readily available tetraethylene glycol and its macrocyclic sulfate. By employing the benzyl group as both a protecting group and a separative tag, multiple chromatographic separations were avoided. With this method, α-amino-ω-methyl-dodecaethylene glycol was prepared on a 53 g scale with high purity and 61% overall yield in eight steps and one chromatographic separation.",10.1021/acs.oprd.5b00270,2015-10-05,0.5808974615171734
Organic Process Research & Development,"Enantioselective Synthesis of the Chiral Pyrrolidine Fragment of Upadacitinib <i>via</i> Chiral Auxiliary Directed Diastereoselective 1,3-Dipolar Cycloaddition","An efficient and elegant enantioselective synthesis of the key chiral pyrrolidine fragment of Upadacitinib (ABT-494) has been described. Oppolzer’s chiral sultam-directed asymmetric 1,3-dipolar cycloaddition was employed as a convenient tool to obtain the desired level of concomitant diastereoselectivity and enantioselectivity in the construction of the 3,4- syn substituted pyrrolidine moiety. The synthesis process was demonstrated as a proof of study on a lab scale and was refined during scale-up to allow for easy disengagement of the chiral auxiliary and its subsequent reuse.",10.1021/acs.oprd.1c00454,2022-05-20,0.580895443900805
Journal of Organic Chemistry,"Structural and Synthetic Investigations of Tanikolide Dimer, a SIRT2 Selective Inhibitor, and Tanikolide <i>seco</i>-Acid from the Madagascar Marine Cyanobacterium <i>Lyngbya majuscula</i>","Tanikolide seco-acid 2 and tanikolide dimer 3, the latter a novel and selective SIRT2 inhibitor, were isolated from the Madagascar marine cyanobacterium Lyngbya majuscula. The structure of 2, isolated as the pure R enantiomer, was elucidated by X-ray experiment in conjunction with NMR and optical rotation data, whereas the depside molecular structure of 3 was initially thought to be a meso compound as established by NMR, MS, and chiral HPLC analyses. Subsequent total synthesis of the three tanikolide dimer stereoisomers 4, 5, and ent-5, followed by chiral GC-MS comparisons with the natural product, showed it to be exclusively the R,R-isomer 5. Tanikolide dimer 3 (= 5) inhibited SIRT2 with an IC(50) = 176 nM in one assay format and 2.4 microM in another. Stereochemical determination of symmetrical dimers such as compound 3 pose intriguing and subtle questions in structure elucidation and, as shown in the current work, are perhaps best answered in conjunction with total synthesis.",10.1021/jo900578j,2009-07-02,0.5808933251632534
Journal of the American Chemical Society,Engineered Cytochrome P450-Catalyzed Oxidative Biaryl Coupling Reaction Provides a Scalable Entry into Arylomycin Antibiotics,"We report herein the first example of a cytochrome P450-catalyzed oxidative carbon–carbon coupling process for a scalable entry into arylomycin antibiotic cores. Starting from wild-type hydroxylating cytochrome P450 enzymes and engineered Escherichia coli, a combination of enzyme engineering, random mutagenesis, and optimization of reaction conditions generated a P450 variant that affords the desired arylomycin core 2d in 84% assay yield. Furthermore, this process was demonstrated as a viable route for the production of the arylomycin antibiotic core on the gram scale. Finally, this new entry affords a viable, scalable, and practical route for the synthesis of novel Gram-negative antibiotics.",10.1021/jacs.2c06019,2022-07-29,0.5808906189838782
Journal of the American Chemical Society,"PdCl<sub>2</sub>-Catalyzed Two-Component Cross-Coupling Cyclization of 2,3-Allenoic Acids with 2,3-Allenols. An Efficient Synthesis of 4-(1‘,3‘-Dien-2‘-yl)-2(5<i>H</i>)-furanone Derivatives","Cross-coupling cyclization reaction between 2,3-allenoic acids 1 and 2,3-allenols 2, in which two allenes functioned differently, was realized to afford 4-(1',3'-dien-2'-yl)-2(5H)-furanone derivatives 3. The reaction may proceed via an oxypalladation, insertion, and beta-hydroxide elimination process. A high E-stereoselectivity of the new formed C=C double bond was observed.",10.1021/ja0500815,2005-04-07,0.580887882952092
Journal of the American Chemical Society,Copper-Catalyzed Enantioselective Intramolecular Alkene Amination/Intermolecular Heck-Type Coupling Cascade,Enantioselective copper-catalyzed cyclization of γ-alkenylsulfonamides and a δ-alkenylsulfonamide in the presence of a range of vinyl arenes results in variously functionalized 2-substituted chiral nitrogen heterocycles via a formal alkene C-H functionalization process. Application of this reaction to the concise synthesis of a 5-HT(7) receptor antagonist is demonstrated.,10.1021/ja211272v,2012-01-17,0.5808867595250455
Synthesis,"A Simple and Efficient Synthesis of Methyl 3,4-Dihydro-2-methyl-2<i>H</i>-1,2-benzothiazine-3-carboxylate 1,1-Dioxide from Saccharin Sodium Salt","A straightforward synthesis of methyl 3,4-dihydro-2-methyl-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide from saccharin sodium salt was achieved in five steps. Methyl 3,4-dihydro-2-methyl-2H-1,2-benzothiazine-3-carboxylate 1,1-dioxide found application as a precursor for the synthesis of a new class of quaternary ammonium derivatives that are potential antiosteoarthritis agents.",10.1055/s-2006-926289,2006-01-01,0.5808817876033577
Journal of the American Chemical Society,Iterative Cyclopropanation:  A Concise Strategy for the Total Synthesis of the Hexacyclopropane Cholesteryl Ester Transfer Protein Inhibitor U-106305,"The first enantioselective total synthesis of the hexacyclopropane natural product U-106305, which is produced by Streptomyces sp. UC 11136, is described in full detail. Considerations on the biosynthesis of U-106305 and its close resemblance to the pentacyclopropane bacterial metabolite FR-900848 ( 10 ) led to the proposal that its previously unknown stereostructure should be represented as 11 . The central C 2 -symmetrical quinquecyclopropane unit of 11 was assembled by repeatedly using a three-step cyclopropane “homologation” sequence in an efficient bidirectional approach. Desymmetrized quinquecyclopropane 23 was converted to dienol 13 which was monocyclopropanated stereo- and regioselectively to provide hexacyclopropane 25 . Deoxygenation was achieved by conversion to thioether 29 and desulfurization. The synthesis was completed by a one-pot deprotection−oxidation−Wittig olefination sequence to give 11 . The synthetically derived material was found to be identical in all respects to an authentic sample of U-106305 thus establishing the stereochemical identity of this natural product for the first time. In the course of our studies, several oligocyclopropane derivatives were found to be crystalline compounds and their structures were determined by X-ray crystallography. Among others, X-ray structures of two diastereomeric heptecyclopropanes 27 and 28 are presented. The synthesis of five analogs of U-106305 including the structural hybrid with FR-900848 ( 41 ) are described. An approach to FR-900848 ( 10 ) using a late desymmetrization of a C 2 -symmetrical quatercyclopropane tetraene 52 is outlined.",10.1021/ja9708326,1997-09-01,0.5808817141400847
Synlett,Synthetic Studies toward Haouamine B: Construction of Indenotetrahydropyridone Skeleton,Synthetic studies on haouamine B are described. The characteristic indenotetrahydropyridone skeleton was constructed by intramolecular Friedel-Crafts alkylation of mesyloxy β-lactam derivative and intramolecular McMurry coupling as key processes.,10.1055/s-0030-1259096,2010-12-14,0.5808809947171272
Organic Letters,Concise Synthesis of the Tricyclic Core of Salimabromide,"A concise synthesis of the tricyclic core 2 of the structurally unique marine myxobacterial natural product salimabromide has been developed. Compound 2 contains the tetraline subunit including the two quaternary centers and the eight-membered ring of salimabromide. Major features for its synthesis include a Lewis base catalyzed Denmark-crotylation for stereoselective construction of the highly hindered quaternary stereocenter, an innovative iodine/selectfluor induced endo-carbocylization, and a unique chemoselective carbonylative lactonization of the eight-membered ring.",10.1021/acs.orglett.5b01231,2015-05-28,0.580879495354775
Organic Letters,Stereoselective Synthesis of the Benzodihydropentalene Core of the Fijiolides,An efficient stereoselective synthesis of the enantiomer of the benzodihydropentalene core of fijiolides A and B has been achieved. The asymmetric conjugate addition of styrylboronic acid to an indenone produced the first stereocenter. Ring C was installed by ring-closing metathesis of a cis disubstituted indanone. Regioselective epoxide opening by NaSePh and subsequent oxidative elimination produced an allylic alcohol. The final introduction of the cyclopentadiene was possible by elimination of an in situ formed triflate.,10.1021/acs.orglett.8b00163,2018-02-16,0.5808787581041902
Organic Letters,Synthesis of the Hydroazulene Ring System of Guanacastepene,"[reaction: see text] A 12-step synthesis of 26, the functionalized hydroazulenone ring of guanacastepene (1), has been completed using the EtAlCl(2)-initiated cyclization of gamma,delta-unsaturated ketone 13 to construct 2,2,3-trisubstituted cyclopentanone 14, the palladium-catalyzed coupling of vinylmagnesium bromide with enol triflate 17 to prepare triene 21, and olefin metathesis of triene 21 to form the key hydroazulene 20.",10.1021/ol0069756,2001-01-19,0.580877933095151
Tetrahedron,A brief and regiospecific synthesis of the late-stage intermediate to 11-deoxyanthracyclinones,,10.1016/s0040-4039(01)91551-5,1984-01-01,0.5808748356825663
Chemical Science,Enantioselective synthesis of Iboga alkaloids and vinblastine via rearrangements of quaternary ammoniums,"We present an efficient and unified strategy for the enantioselective syntheses of various <italic>iboga</italic> alkaloids and vinblastine, involving gold-catalyzed oxidation and Stevens rearrangement. New vinblastine analogs were prepared by our 10-step synthesis.",10.1039/c6sc00932h,2016-01-01,0.5808729839049946
Organic Letters,SmI<sub>2</sub>-Mediated Coupling of Nitrones and <i>tert</i>-Butanesulfinyl Imines with Allenoates: Synthesis of β-Methylenyl-γ-lactams and Tetramic Acids,"Nitrones and tert-butanesulfinyl imines undergo conjugate addition to alkyl allenoates under SmI(2)-mediated reductive coupling conditions to produce novel β-methylenyl-substituted γ-amino esters. The latter were readily transformed into the corresponding β-methylenyl-γ-lactams by simple zinc reduction (N-hydroxy amines) or by acid hydrolysis (sulfinamides). The diastereoselective preparation of various β-methylenyl-γ-lactams offers a route to tetramic acids, the key structural features of an important class of bioactive natural products.",10.1021/ol300550x,2012-04-10,0.5808718319147241
Tetrahedron,Synthetic studies related to compactin and mevinolin: A new synthesis of the lactone system.,,10.1016/s0040-4039(01)81171-0,1984-01-01,0.5808635379791365
Tetrahedron,"Asymmetric synthesis of chiral 2-fluorinated 1,3-propanediols and its application to the preparation of monofluorinated chiral synthon",,10.1016/s0040-4039(98)01687-6,1998-10-01,0.5808613350813919
Tetrahedron,A new synthesis of substituted butenolides via cation-initiated ring expansion/elimination of β-lactones,,10.1016/s0040-4039(00)60304-0,1993-02-01,0.5808577724061279
Tetrahedron,"Synthesis of cyclic hydropyran oligolides with convergent amine, amide, phosphonate and furan appendages",,10.1016/s0040-4039(97)00422-x,1997-04-01,0.5808558747166773
Tetrahedron,Asymmetric synthesis of cis -aminochromanol,,10.1016/s0040-4039(01)01907-4,2001-12-01,0.5808554585285888
European Journal of Organic Chemistry,"A Convenient Synthesis of 1‐Deoxy‐8a‐<i>epi</i>‐Castanospermine Diastereoisomers (6<i>R</i>,7<i>R</i>,8<i>S</i>,8a<i>S</i>)‐6,7,8‐Trihydroxyindolizidine and (6<i>R</i>,7<i>R</i>,8<i>R</i>,8a<i>S</i>)‐6,7,8‐Trihydroxyindolizidine","Abstract An efficient synthesis of (6 R ,7 R ,8 S ,8a S )‐6,7,8‐trihydroxyindolizidine and (6 R ,7 R ,8 R ,8a S )‐6,7,8‐trihydroxyindolizidine is described from readily available N ‐BOC‐ L ‐proline, (BOC = tert ‐butoxycarbonyl) which involves the addition of ethyl lithiopropiolate to the aldehyde derived from N ‐BOC‐ L ‐proline as a key step, then cyclization to construct indolizidine skeletons and asymmetric dihydroxylation. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2003)",10.1002/ejoc.200200412,2003-05-01,0.5808538354590803
Journal of the American Chemical Society,"Convergent Route to <i>ent</i>-Kaurane Diterpenoids: Total Synthesis of Lungshengenin D and 1α,6α-Diacetoxy-<i>ent</i>-kaura-9(11),16-dien-12,15-dione","The Hoppe’s homoaldol reaction of a cyclo-hexenyl carbamate with an aldehyde followed by an unprecedented BF 3 ·OEt 2 mediated intramolecular Mukaiyama–Michael-type reaction affords the tetracyclic core structure of ent -kaurane diterpenoids. The usage of this convergent approach for assembling these natural products is demonstrated by the first asymmetric total syntheses of two highly oxidized ent -kaurane diterpenoids: Lungshengenin D and 1α,6α-diacetoxy- ent -kaura-9(11),16-dien-12,15-dione.",10.1021/jacs.7b00140,2017-02-10,0.5808451711260215
Journal of Organic Chemistry,"Synthesis of 2‘-Substituted 4-Bromo-2,4‘-bithiazoles by Regioselective Cross-Coupling Reactions","The synthesis of the title compounds (1) was achieved in two steps starting from readily available 2,4-dibromothiazole (2). In a regioselective Pd(0)-catalyzed cross-coupling step, compound 2 was converted into a variety of 2-substituted 4-bromothiazoles 3 (10 examples, 65-85% yield). Alkyl and aryl zinc halides were employed as nucleophiles to introduce an alkyl or aryl substituent. The Sonogashira protocol was followed to achieve an alkynyl-debromination. Bromo-lithium exchange at carbon atom C-4 and subsequent transmetalation to zinc or tin converted the 4-bromothiazoles 3 into carbon nucleophiles which underwent a second regioselective cross-coupling with another equivalent of 2,4-dibromothiazole (2). The Negishi cross-coupling gave high yields of the 2'-alkyl-4-bromo-2,4'-bithiazoles 1a-g (88-97%). The synthesis of the 2'-phenyl- and 2'-alkynyl-4-bromo-2,4'-bithiazoles 1h-j required a Stille cross-coupling that did not proceed as smoothly as the Negishi cross-coupling (58-62% yield). The title compounds which were accessible in total yields of 38-82% are versatile building blocks for the synthesis of 2,4'-bithiazoles.",10.1021/jo025661o,2002-07-11,0.5808428127620225
Tetrahedron,Stereocontrol by diethylaluminum chloride in the addition of 2-lithiofuran and N-methyl-2-lithioimidazole to α-alkoxy nitrones. Total synthesis of 5-O-carbamoylpolyoxamic acid.,,10.1016/s0040-4039(00)73939-6,1993-01-01,0.5808390865150478
Tetrahedron,Synthesis of cyclic olefins via Mitsunobu C-alkylation followed by Ramberg-Bäcklund ring contraction,,10.1016/j.tetlet.2018.06.014,2018-06-05,0.5808347937132481
Angewandte Chemie International Edition,Total Synthesis of Synechoxanthin through Iterative Cross‐Coupling,"The choice is yours: The first total synthesis of the antioxidant carotenoid synechoxanthin was achieved through a novel iterative cross-coupling approach in which the polarity of the bifunctional building blocks is reversed to match the preferred polarity for CC bond formation (see scheme). The convergent, stereocontrolled, and flexible nature of this synthesis enables systematic studies of the biological activities of this natural product.",10.1002/anie.201102688,2011-06-16,0.5808330170609433
Synthesis,Synthesis of Indole Derivatives by Cyclization of Oxo <i>N</i>-Acyliminium Ions,All articles of this category (opens in new window),10.1055/s-2008-1072532,2008-04-25,0.58083198884919
Organic Letters,Chemodivergent and Stereoselective Access to Fused Isoxazoline Azetidines and Thietanes through [3 + 2]-Cycloadditions,"By combining efficient methodologies for the preparation of substituted azetines and thietes with a highly regio- and diastereoselective [3 + 2]-cycloaddition, a straightforward pathway for the synthesis of fused isoxazoline azetidines and thietanes has been designed. With minimal steps and starting from commercial sources, a new library of elaborated architectures was synthesized opening up a new class of molecules with large potential in pharmacology. Finally, a retro [2 + 2]-cycloaddition leading to substituted isoxazoles is described.",10.1021/acs.orglett.8b02848,2018-10-23,0.5808316437588324
Journal of Organic Chemistry,"A One-Step Synthesis of 2,4-Unsubstituted Quinoline-3-carboxylic Acid Esters from <i>o</i>-Nitrobenzaldehydes","A straightforward and efficient one-step procedure for the synthesis of 2,4-unsubstituted quinoline-3-carboxylic acid ethyl esters is described. The simple reductive cyclization is carried out by treating various substituted o-nitrobenzaldehydes with inexpensive, commercially available 3,3-diethoxypropionic acid ethyl ester and SnCl(2).2H(2)O in refluxing ethanol.",10.1021/jo100392x,2010-04-26,0.580810395255296
Tetrahedron,A simple route to novel functionalized tetrathiafulvalene vinylogues,,10.1016/j.tetlet.2005.06.056,2005-07-02,0.5808095194464956
Synlett,Thieme Chemistry Journal Awardees - Where Are They Now? Approaches to Tagetitoxin and its Decarboxy Analogue from d-Glucose,"A fifteen-step route has been developed from 1,6-anhydro-β-d-glucopyranose to a C-alkynyl glycoside precursor of decarboxytagetitoxin. Preparation of 1,6-anhydro-5-C-vinyl-β-d-gluco-pyranose, a potential precursor of tagetitoxin, is also described.",10.1055/s-0029-1218525,2009-11-27,0.5808075533066093
Tetrahedron,Pyridinium amide-based simple synthetic receptor for selective recognition of dihydrogenphosphate,,10.1016/j.tetlet.2009.09.043,2009-09-13,0.5808011949799327
Journal of Organic Chemistry,One-Pot Synthesis of Multisubstituted Butyrolactonimidates: Total Synthesis of (−)-Nephrosteranic Acid,"Multisubstituted chiral butyrolactonimidates have been synthesized via a one-pot, three-step cascade reaction in which (R)-N-tert-butanesulfinyl imidates and α,β-unsaturated diesters undergo highly stereoselective Michael addition, anion-oxidative hydroxylation, and cyclization. The synthesized butyrolactonimidates are versatile intermediates for preparation of substituted butyrolactones and furans. The usefulness of this cascade reaction is demonstrated through the concise total synthesis of natural product (-)-nephrosteranic acid.",10.1021/jo5029166,2015-02-11,0.5807996375062418
Synthesis,Cyclization of<i>o</i>-(Methylthio)-anilides with Phosphonitrile Dichloride; Synthesis of 2-Substituted Benzothiazoles,The synthesis of 2-substituted benzothiazoles by cyclization of o-(methylthio)-anilides with phosphonitrile dichloride is reported,10.1055/s-1977-24625,1977-01-01,0.5807990336208867
Tetrahedron,Palladium-catalyzed coupling of alkenyl iodides with ethynyl oxiranes: Synthesis of epoxy enediyne core intermediates related to neocarzinostatin chromophore,,10.1016/s0040-4039(97)82957-7,1996-12-01,0.5807889795799294
Synthesis,"Synthesis of Macrocycles Containing 1,2,3-Triazole Motifs","A new procedure for the preparation of macrocycles containing 1,2,3-triazole motifs is developed. The macrocyclic precursor is constructed by repetition of a series of steps which include cycloaddition of an azide with an alkyne, alkylation of a carboxylic acid with propargyl bromide and formation of an azide from an amino group. The order of the steps and the size of the connected fragments are determined by the desired ring size. Chromatographic purification techniques for the poorly soluble final products are also described.",10.1055/s-0031-1290760,2012-03-29,0.5807859770121735
Organic Letters,"Synthesis of 2‘,3‘-Dideoxy-6‘,6‘-difluorocarbocyclic Nucleosides","2',3'-Dideoxy-6',6'-difluorouracils, a novel series of gem-difluoromethylenated carbocyclic nucleosides, were synthesized from (Z)-but-2-ene-1,4-diol in 14 steps. A notable step was the construction of the carbocyclic ring via ring-closing metathesis and the incorporation of gem-difluoromethylene group by way of silicon-induced Reformatskii-Claisen reaction of chlorodifluoroacetic ester 3.",10.1021/ol0482947,2004-10-21,0.5807831210946808
Organic Letters,Synthesis of Multisubstituted Pyridines,"By utilizing amino allenes, aldehydes, and aryl iodides as readily available building blocks, a simple and modular synthesis of multisubstituted pyridines with flexible control over the substitution pattern has been achieved. The method employs a two-step procedure involving the preparation of ""skipped"" allenyl imines and a subsequent palladium-catalyzed cyclization.",10.1021/ol303246b,2012-12-28,0.5807756442282805
Synlett,Stereocontrol in the Synthesis of β-Lactams Arising from the Interlocked Structure of Benzylfumaramide-Based Hydrogen-Bonded [2]Rotaxanes,"β-Lactams are highly valuable compounds due to their antibiotic activity. Among the number of well-established methodologies for building this privileged scaffold, our research group has settled on a novel synthetic approach for their preparation. This Account focuses on our latest progress in the synthesis of these compounds through a novel base-promoted intramolecular cyclization of benzylfumaramide-based rotaxanes. The mechanical bond plays a significant role in the process by activating the cyclization inside the macrocycle void, avoiding the formation of byproducts and fully controlling the diastereoselectivity. Further investigations on this transformation led to the formation of ­enantioenriched 2-azetidinones. The cyclization of enantiopure interlocked α-methylbenzylfumaramides allows the formation of two new stereogenic centers in the lactamic four-membered ring, one of them a quaternary carbon, keeping the initial configuration of the chiral group of the starting material. 1 Introduction 1.1 Mechanically Interlocked Molecules and Applications 1.2 Chemical Stabilization of the Mechanical Bond 2 Literature Methods for 4-exo-trig Ring Closures of Fumaramides for the Synthesis of β-Lactams 3 Our First Encounter with Interlocked β-Lactams 3.1 An Unexpected Result in Our Laboratory 3.2 Finding the Optimal Reaction Conditions 3.3 Elucidating the Effects of the Mechanical Bond 4 Diastereoselective Synthesis of Interlocked and Non-Interlocked β-Lactams 5 Asymmetric Cyclization of Enantiopure Interlocked Fumaramides 6 Conclusions",10.1055/s-0037-1611705,2019-01-18,0.58077288844809
Synlett,Diastereo- and Facially Selective Imino-Diels–Alder Cycloaddition of 2-Azeditinone-Tethered 1-Azadiene: Synthesis of Functionalized (2-Oxo-4-styrylazetidin-3-yl)–Pyridine Hybrids,"Highly diastereo- and π-facially selective imino Diels–Alder cycloadditions of 3-allylideneamino-2-azetidinones having stereocentres at its α- and β-positions, with symmetrical dienophiles leading to the formation of biologically potent (2-oxo-4-styrylazetidin-3-yl)–pyridine hybrids have been reported.",10.1055/s-0034-1379505,2015-01-08,0.5807658149133387
Tetrahedron,Stereospecific synthesis of (+)-oxybiotin from D-xylose. Preparation of the final chiral (+)-oxybiotin precursor,,10.1016/s0040-4039(00)96827-8,1987-01-01,0.580762339487896
Synthesis,"A New Synthesis of 2,4-Dioxo-1,2,3,4,6,7,12,12b-octahydroindolo[2,3-<i>a</i>]quinolizine",,10.1055/s-1985-31222,1985-01-01,0.5807608991422606
Journal of Organic Chemistry,"New Building Block for Polyhydroxylated Piperidine:  Total Synthesis of 1,6-Dideoxynojirimycin","(3R,4S)-3-Hydroxy-4-N-allyl-N-Boc-amino-1-pentene 10, an important precursor for the synthesis of polyhydroxylated piperidines, has been achieved as a single diastereomer without racemization via vinyl Grignard addition to N-Boc-N-allyl aminoaldehyde 9, which was derived from an enantiopure natural amino acid. Having forged a tetrahydropyridine ring scaffold 13 from 10 in 85% yield via RCM using Grubbs II catalyst, we were able to effect its stereodivergent dihydroxylation, via a common epoxide intermediate to yield a range of interesting hydroxylated piperidines, including ent-1,6-dideoxynojirimycin (ent-1,6-dDNJ) 1 (28% overall yield) and 5-amino-1,5,6-trideoxyaltrose 2 (29% over all yield) in excellent dr. To the best of our knowledge, our synthesis of ent-1,6-dDNJ 1 is the most expeditious to date.",10.1021/jo702480y,2008-03-12,0.5807558321559984
Tetrahedron,(Chloro-phenylthio-methylene)dimethylammonium chloride (CPMA): a new coupling reagent for the formation of ester and amide bond,,10.1016/s0040-4039(02)01763-x,2002-10-01,0.5807544056988246
Synthesis,"An Expedient and Practical Approach to Functionalized 3-Aza-, 3-Oxa-, and 3-Thiabicyclo[3.3.1]nonane Systems","The synthesis of a number of heterobicyclo[3.3.1]nonane derivatives possessing carbonyl, amino, or carboxyl groups is reported. The synthetic scheme is concise and practical, based on optimized reaction conditions for each step and an orthogonal protection group strategy. Procedures for the key synthetic steps (double annulation of α-bromomethyl acrylates to enamines and a Caglioti reaction) were improved significantly. This makes the compounds attractive for medicinal chemistry as potential chemically diverse 3D-scaffolds applicable in drug design.",10.1055/s-0034-1379456,2014-11-14,0.580748587192943
Journal of Organic Chemistry,Visible-Light-Induced Decarboxylation Coupling/Intramolecular Cyclization: A One-Pot Synthesis for 4-Aryl-2-quinolinone Derivatives,"A visible-light-induced decarboxylation coupling/intramolecular cyclization is reported. The one-pot synthesis system provides mild, efficient, and atom economical access to the synthesis of 4-aryl-2-quinolinone derivatives. It is notable that the necessary oxidant in the traditional decarboxylation coupling is replaced by the visible-light irradiation in this paper. In addition, the HBV inhibitor is synthesized by the one-pot synthesis system in an atom economical manner.",10.1021/acs.joc.7b02979,2018-01-11,0.5807461583765939
Journal of Organic Chemistry,Synthetic Route Development for the Laboratory Preparation of Eupalinilide E,"Following the discovery that the guaianolide natural product eupalinilide E promotes the expansion of hematopoietic stem and progenitor cells; the development of a synthetic route to provide laboratory access to the natural product became a priority. Exploration of multiple synthetic routes yielded an approach that has permitted a scalable synthesis of the natural product. Two routes that failed to access eupalinilide E were triaged either as a result of providing an incorrect diastereomer or due to lack of synthetic efficiency. The successful strategy relied on late-stage allylic oxidations at two separate positions of the molecule, which significantly increased the breadth of reactions that could be used to this point. Subsequent to C-H bond oxidation, adaptations of existing chemical transformations were required to permit chemoselective reduction and oxidation reactions. These transformations included a modified Luche reduction and a selective homoallylic alcohol epoxidation.",10.1021/acs.joc.7b00266,2017-04-25,0.5807454979021063
Synlett,Alkyne-Assisted Approach to the Formal Synthesis of Antibiotic Macrolide (-)-A26771B,"A stereoselective formal synthesis of a 16-membered antibiotic macrolide (-)-A26771B is described starting from (R)-propylene oxide and (+)-diethyl tartrate. Key steps involved in this alkyne-assisted convergent approach are alkyne zipper reaction, Cadiot-Chodkiewicz coupling, and Yamaguchi macrolactonization.",10.1055/s-0031-1290130,2012-01-01,0.5807407849072633
Journal of Organic Chemistry,Total Synthesis of the Plant Growth Promoter Auxofuran Featuring a Gold(I) Catalyzed Furan Formation,"A concise synthesis of auxofuran ( 1 ) was developed. Starting with a Sonogashira cross-coupling reaction, enynol ( 10 ) was prepared. A gold(I) catalyzed cycloisomerization led to disubstituted furan 12 . Via an intramolecular Friedel–Crafts cyclization, a dihydrobenzofuranone was obtained. Functional group manipulations, including benzylic oxidation, led to the target molecule.",10.1021/acs.joc.0c00408,2020-05-20,0.5807400093346792
Tetrahedron,"Two synthetic routes to 1,3,5-triaryl-2-phenylimino-4,6-dioxohexahydro-s-triazines",,10.1016/s0040-4039(01)82582-x,1974-01-01,0.5807362575499865
Tetrahedron,Synthetic routes to singly and doubly bridged porphyrins,,10.1016/s0040-4039(01)94974-3,1978-01-01,0.5807362575499865
Tetrahedron,Synthetic routes to cyclopropylidenecarbinols and to cyclopropylidienes,,10.1016/s0040-4039(01)93298-8,1981-01-01,0.5807362575499865
Tetrahedron,Synthetic routes to 4′-hydroxymethylnucleosides,,10.1016/s0040-4039(01)92658-9,1977-01-01,0.5807362575499865
Synthesis,First Asymmetric Synthesis of Stigmolone: The Fruiting Body Inducing Pheromone of the Myxobacterium Stigmatella Aurantiaca,"All articles of this category The asymmetric synthesis of ( S )- and ( R )-stigmolone [( S )- and ( R )- 1 ], an aggregation pheromone of the myxobacterium Stigmatella aurantiaca , starting from 4-methylpentan-2-one is described. The stereogenic centre at the C-5 position of the pheromone was generated via the SAMP/RAMP hydrazone method with high enantiomeric purity. It could be shown again that both enantiomers induce the fruiting body formation of the myxobacterium at concentrations of 1.0-30.0 nM. asymmetric synthesis - pheromones - hydrazones - natural products - Stigmatella aurantiaca",10.1055/s-2000-8219,2000-01-01,0.5807317543565902
Synthesis,"Asymmetric Synthesis of d-Proline, d-Pipecolic Acid, (2R,3S,4R)-3,4-Dihydroxyproline, and 1,4-Dideoxy-1,4-imino-d-talitol from a Common Precursor","Methodology involving stereoselective aza-Michael addition and ring-closing metathesis as key steps has been developed for the preparation of (2 R )-pipecolic acid, (2 R )-proline, (2 R ,3 S ,4 R )-3,4-dihydroxyproline, and the known glycosidase inhibiting azasugar 1,4-dideoxy-1,4-imino- d -talitol from a common starting material namely ( R )-cyclohexylideneglyceraldehyde in good overall yields.",10.1055/s-0034-1378452,2014-07-25,0.5807271525598513
Tetrahedron,"A highly efficient, asymmetric synthesis of blastidic acid: the β-amino acid component of the antibiotic, (+)-blasticidin S",,10.1016/j.tetlet.2005.08.096,2005-09-07,0.5807264794081264
Tetrahedron,"Synthesis of 1-O-(2-oxo-benzo-1,3,2-dioxaphosphaocan-2-yl)-myo-inositol and 3,5-dideoxy-1-O-(2-oxo-benzo-1,3,2-dioxaphosphaocan-2-yl)-myo-inositol as prodrugs of inositolmonophosphatase ligands",,10.1016/s0040-4039(98)00941-1,1998-07-01,0.5807245796623196
Journal of Organic Chemistry,"Asymmetric Total Syntheses of Sarglamides A, C, and E","The asymmetric total syntheses of sarglamides A, C, and E in concise and protecting group free fashion is disclosed. Key steps involve an endo -selective Diels–Alder reaction to construct the bicyclo[2.2.2]nonane framework, a nucleophilic addition and an intramolecular aza -Michael addition to install the pyrrolidine ring, and a final cinnamoylation reaction. Sarglamide C is biomimetically transformed into E through a Brønsted acid mediated oxy-cyclization. Sarglamide D is also accessible from C based on Yue’s research. This work provides an efficient asymmetric approach to the syntheses of sarglamides and also provides insights into understand the plausible biogenetic pathway of these monoterpenoid–indolidinoid hybrid structures.",10.1021/acs.joc.4c02666,2024-12-30,0.5807227156779684
Tetrahedron,Biomimetic entry to chiral epoxide synthesis novel asymmetric induction using chiral anchimeric assistance,,10.1016/s0040-4039(00)84258-6,1986-01-01,0.5807187035341075
Tetrahedron,Synthetic studies on FR182877: an asymmetric synthesis of the AB ring moiety of FR182877 via a diastereoselective intramolecular Diels–Alder reaction,,10.1016/s0040-4039(02)00536-1,2002-04-01,0.5807137496010442
Synthesis,An Asymmetric Synthesis of (-)-Prelactone B,All articles of this category (opens in new window),10.1055/s-2005-916009,2005-09-23,0.5807116939871685
Tetrahedron,"An efficient synthesis for a new class antimalarial agent, 7-(2-carboxyethyl)-1,3-dihydro-1-hydroxy-2,1-benzoxaborole",,10.1016/j.tetlet.2011.05.088,2011-06-03,0.5807115649083956
Organic Letters,A Unified Total Synthesis of Aspergillides A and B,"An enantioselective total synthesis of aspergillides A and B has been accomplished based on a unified strategy, wherein a hydroxy-directed, highly chemoselective olefin cross-metathesis and a diastereoselective intramolecular oxa-conjugate cyclization were employed to forge the 2,6-substituted tetrahydropyran substructure.",10.1021/ol100463a,2010-03-18,0.5807081756820477
Tetrahedron,Efficient (bromodimethyl)sulfonium bromide mediated synthesis of benzimidazoles,,10.1016/j.tetlet.2006.11.018,2006-11-22,0.580704220917098
Synthesis,Asymmetric Synthesis of Both Enantiomers of a δ-Lactone Analogue of Muricatacin,"The asymmetric synthesis of both enantiomers of the δ-lactone analogue of the antitumoral natural product γ-lactone muricatacin has been carried out. Initial attempts to also synthesize the natural product proved unsuccessful due to the poor reactivity of the Grignard reagent derived from 2-(bromomethyl)-1,3-dioxolane. The designed synthetic route enabled us to increase the ring size to generate the δ-lactone analogue employing Sharpless asymmetric epoxidation and ZrCl 4 -catalyzed intramolecular acetalization as the key steps.",10.1055/s-0033-1340850,2014-02-21,0.5807040097153295
Angewandte Chemie International Edition,An Efficient Total Synthesis of (±)-Galanthamine,"Intramolecular Heck reaction of 3 generates a spiro quaternary C atom—a key step in an efficient synthesis of galanthamine (1). Galanthamine can be readily obtained from the spiro tricyclic dienone 2, which was prepared by nonclassical dehydrogenation of the corresponding α,β-unsaturated ketone.",10.1002/1521-3773(20011217)40:24<4745::aid-anie4745>3.0.co;2-5,2001-12-17,0.5806927556930531
Organic Letters,"Stereoselective Synthesis of Carbocyclic <scp>l</scp>-4‘-Fluoro-2‘,3‘-dideoxyadenosine","[formula: see text] L-(1'S,3'S)-9-[3-Fluoro-3-(hydroxymethyl)cyclopentan-1-yl]adenine 15 has been synthesized from ester 2, which can be conveniently prepared from 2,3-isopropylidene-D-glyceraldehyde 1 in six steps. The key ring closure has been accomplished through an intramolecular nucleophilic substitution reaction.",10.1021/ol005665k,2000-04-14,0.5806917953416546
Tetrahedron,"Synthesis of α,β-unsaturated spirolactams by intramolecular cyclization of endocyclic N-Acyliminium ions.",,10.1016/0040-4039(95)01568-3,1995-10-01,0.5806917121859623
Tetrahedron,"Synthesis of marine bisindole alkaloids, hamacanthins A and B through intramolecular transamidation–cyclization",,10.1016/j.tetlet.2003.09.184,2003-11-07,0.5806917121859623
Tetrahedron,A practical highly selective oxybromination of phenols with dioxygen,,10.1016/j.tetlet.2007.06.093,2007-06-26,0.5806883881274646
Tetrahedron,A novel asymmetric reduction of imines with chiral sodium triacyloxyborohydrides,,10.1016/s0040-4039(01)91331-0,1981-01-01,0.5806876614455172
Organic Process Research & Development,"Development and Demonstration of a High-Volume Manufacturing Process for a Key Intermediate of Dalcetrapib: Investigations on the Alkylation of Carboxylic Acids, Esters, and Nitriles","Dalcetrapib ( 1 ), a cholesterol ester transfer protein inhibitor, was a clinical candidate at Roche until 2012. By this time, manufacturing processes capable of efficiently delivering kilotonne annual volumes of Dalcetrapib had been developed and demonstrated at the commercial scale. This paper describes the development of synthetic routes for the manufacture of key intermediate 1-(2-ethylbutyl)-cyclohexanecarboxylic acid ( 2 ) and selection of the preferred process. The selected process involves novel methods for the α-alkylation of a nitrile using methylmagnesium chloride as a non-nucleophilic base and for the hydrolysis of a highly sterically hindered nitrile using sodium hydroxide in methanol/water at 200 °C. The performance of the process at plant scale is reported. Safety considerations and the chemistry behind the formation of side-products are discussed. Continuous-flow processes with potential operational benefits were demonstrated at laboratory scale for both the alkylation and the nitrile hydrolysis steps. A possible second-generation process for the manufacture of acid 2 is also described, which involves a novel reductive alkylation of benzoic acid.",10.1021/acs.oprd.3c00304,2023-11-13,0.5806874797523178
European Journal of Organic Chemistry,"Highly Regioselective Addition of Organozinc Reagents to 2‐Oxo‐1,2‐dihydropyrimidine‐5‐carboxylates Activated by BF<sub>3</sub>·OEt<sub>2</sub>: Synthesis of 2‐Oxo‐1,2,3,4‐tetrahydropyrimidine‐5‐carboxylates","Abstract The incorporation of alkyl as well as phenyl groups at C‐4, a key position of 2‐oxo‐1,2,3,4‐tetrahydropyrimidine‐5‐carboxylates, responsible for antagonist/agonist switching of the calcium channel blocking activity of these compounds, has been achieved by the addition of organozinc reagents to the corresponding 2‐oxo‐1,2‐dihydropyrimidine‐5‐carboxylate derivatives catalysed by BF 3 OEt 2 .",10.1002/ejoc.201300539,2013-08-02,0.5806836900048961
Synlett,Efficient Synthesis of OpticallyActive Gallocatechin-3-gallate Derivatives via 6-<i>endo</i>-Cyclization,"Optically active dihydrobenzopyran derivatives are synthesized by 6-endo cyclization of corresponding epoxy-phenol, which is readily derived from the enantioselective epoxidation of 1,3-diarylpropene. Synthetic dihydrobenzopyrans are converted into (-)-5,7-dideoxy-gallocatechin gallate as well as (-)-5,7-dideoxy-epigallocatechin derivative.",10.1055/s-0028-1087371,2008-11-26,0.5806764708781071
Synthesis,"Synthesis of New β-Carboline Derivatives via 1,7-Electrocyclisation of Azomethine Ylides","A new route to the benzo[5,6]azepino[2,1-a]-β-carboline and indazolo[3,2-a]-β-carboline ring systems has been developed via the 1,7-dipolar electrocyclisation reactions of azomethine ylides derived from easily available β-carboline derivatives.",10.1055/s-2006-926400,2006-04-01,0.580676456256144
Synlett,"Short, Enantioselective Total Syntheses of Fugomycin and Desoxyfugomycin via Sonogashira Alkynylation of α-Bromobutenolides","The potent antifungal antibiotics (+)-fugomycin and (+)-desoxyfugomycin were synthesized in 3–4 steps with high overall efficiency (51–53%) and optical purity (ee > 97%). The syntheses illustrate a highly effective protocol for accomplishing racemization-free Sonogashira coupling of chiral α-bromobutenolides, and the usefulness of the Movassaghi–Jacobsen method for preparing the latter from epoxides.",10.1055/s-0033-1339926,2013-10-28,0.5806728827046276
Synthesis,A New Efficient Synthesis of Antiviral Methylenecyclopropane Analogs of Purine Nucleosides,,10.1055/s-1998-2163,1998-10-01,0.5806713529497893
Organic Letters,Synthesis of Enantiopure Substituted Piperidines <i>via</i> an Aziridinium Ring Expansion,"Herein we report a novel methodology for the asymmetric synthesis of 3-substituted piperidines from readily available chiral building blocks. This method, which features a novel irreversible dihydropyrole-tetrahydropyridine ring expansion, allows the introduction of a large variety of substituents at the 3-position and permits substitution at the 2- and 6-position giving mono-, di-, or trisubstituted piperidines with high diastereocontrol.",10.1021/ol201349k,2011-06-28,0.5806712719961271
Tetrahedron,A facile synthesis of novel tricyclic 4-pyridones,,10.1016/j.tetlet.2014.11.003,2014-11-10,0.5806685433560632
Tetrahedron,A novel and facile synthesis of tetraacylbenzenes,,10.1016/s0040-4039(00)73486-1,1994-09-01,0.5806685433560632
Tetrahedron,"A novel and facile synthesis of 7,8-diacylcoumarins",,10.1016/j.tetlet.2007.07.202,2007-08-03,0.5806685433560632
Organic Letters,Pharmacophore-Directed Retrosynthesis Applied to Rameswaralide: Synthesis and Bioactivity of <i>Sinularia</i> Natural Product Tricyclic Cores,"A pharmacophore-directed retrosynthesis strategy applied to rameswaralide provided simplified precursors bearing the common 5,5,6 (red) and 5,5,7 (blue) skeleton present in several cembranoid and norcembranoids from Sinularia soft corals. Key steps include a Diels–Alder lactonization organocascade delivering the common 5,5,6 core and a subsequent ring expansion affording a 5,5,7 core serviceable for the synthesis of rameswaralide. Initial structure–activity relationships of intermediates en route to the natural product have revealed interesting differential and selective cytotoxicity.",10.1021/acs.orglett.9b02713,2019-09-09,0.5806663847472621
Tetrahedron,Rapid and efficient stereocontrolled synthesis of C-3′-ethynyl ribo and xylonucleosides by organocerium additions to 3′-ketonucleosides,,10.1016/0040-4039(94)02434-d,1995-02-01,0.5806643572449384
Tetrahedron,A rapid and efficient synthesis of ribonucleotides,,10.1016/s0040-4039(01)85821-4,1978-01-01,0.5806643572449384
Tetrahedron,"Synthesis of acenes via coupling of 1,4-dilithiobutadienes with diiodoarenes in the presence of CuCl",,10.1016/j.tetlet.2009.02.191,2009-03-02,0.5806613910219814
Journal of Organic Chemistry,Synthesis of Three Marine Natural Sesterterpenolides from Methyl Isoanticopalate. First Enantioselective Synthesis of Luffolide,"[Reaction: see text]. The synthesis of three marine sponge metabolites, luffolide (4), 5, and 6, are described for the first time, establishing the absolute configuration of these compounds. The key intermediate, aldehyde 17, was obtained from methyl isoanticopalate, 11. The addition of 3-furyllithium to 17 and subsequent photochemical oxidation give the gamma-hydroxybutenolide 5 and its epimer at C-16. Sesterterpenolide 6 is obtained by dehydration of 5. From the key aldehyde 17, luffolide (4) was obtained in six steps.",10.1021/jo0515529,2005-10-15,0.5806605212069058
Synlett,Stereoselective Synthesis of (-)-Trachelanthamidine via Palladium-Catalysed Intramolecular Allylation,"A stereoselective synthesis of ()-trachelanthamidine has been developed, employing a palladium-catalysed cyclisation as the key step.",10.1055/s-2006-949605,2006-08-01,0.5806584785154874
Tetrahedron,One-step synthesis of dipyrromethanes in water,,10.1016/s0040-4039(03)00785-8,2003-04-30,0.5806568012184459
Tetrahedron,Stereocontrolled approaches to the key intermediate of 1β-methylthienamycin,,10.1016/s0040-4039(00)94390-9,1990-01-01,0.5806529635858656
Tetrahedron,A new synthesis of γ-hydroxyvinylstannanes and silanes utilizing β-stannylvinyl and β-silyvinyl sulfones,,10.1016/s0040-4039(00)88253-2,1983-01-01,0.5806517429113449
Tetrahedron,Biomimetic polyene cyclizations. Participation of the trimethylsilylacetylenic group as a terminator and the total synthesis of a D-homosteroid,,10.1016/s0040-4039(01)94823-3,1978-01-01,0.5806491306783008
Tetrahedron,"First syntheses of (2S, 3S)- and (2S, 3R)-m-prenyl-β-hydroxytyrosine derivatives: Bioactive amino acid fragment of a substance P antagonist novel cyclic heptapeptide",,10.1016/s0040-4039(96)02298-8,1997-01-01,0.5806423427637933
Organic Letters,Scalable Protecting-Group-Free Total Synthesis of Resibufogenin and Bufalin,"A chemoenzymatic synthesis access to resibufogenin and bufalin was developed in seven steps without protecting groups. Starting with androstenedione (AD), an α-OH was introduced directly at C14 by hydroxylase P-450 lun, which was further used as the directing group for hydrogenation to fully control the C17 configuration in the β-orientation after Suzuki cross-coupling. Dehydration of 14α-OH followed by an epoxidation delivered resibufogenin. Simultaneously, bufalin was also obtained via a challenging anaerobic Mukaiyama hydration.",10.1021/acs.orglett.4c03433,2024-11-04,0.5806313883955885
Organic Letters,Total Synthesis of (−)-Cylindricine H,"High Resolution Image Download MS PowerPoint Slide Starting from ( R )-phenylglycinol-derived tricyclic lactam 1, the enantioselective synthesis of (−)-cylindricine H is reported. From the stereochemical standpoint, the key steps are the stereoselective generation of the quaternary C 10 stereocenter, the stereoselective introduction of the C 4 acetoxy and C 2 butyl substituents taking advantage of the lactam carbonyl functionality, and the assembly of the pyrrolidine ring with the required functionalized one-carbon chain at C 13 by intramolecular opening of an epoxide.",10.1021/acs.orglett.2c02004,2022-07-18,0.5806292733369524
Organic Letters,"Second Generation Synthesis of C27−C35 Building Block of E7389, a Synthetic Halichondrin Analogue","A practical method is reported to synthesize E7389 C27-C35 building block 13 from 1,2-O-isopropylidene-alpha-D-5-deoxyglucurono-6,3-lactone (3). This synthesis relies on two key processes: (1) C34/C35-diol is introduced via asymmetric dihydroxylation with dr = 3:1, with the undesired C34-diastereomer effectively removed by crystallization of 11, and (2) the C30 PhSO2CH2 group is introduced stereoselectively (>100:1) via hydrogenation of 12 in the presence of the Crabtree catalyst. The reported synthesis is practically free from chromatographic separation.",10.1021/ol9016589,2009-09-16,0.5806268624405202
European Journal of Organic Chemistry,A New Facet of Azatriene Reactivity: A Short Cut to 5‐Amino‐3‐methyl‐4‐(1<i>H</i>‐pyrrol‐1‐yl)thiophene‐2‐carboxylates and 5‐Amino‐3‐methyl‐4‐(1<i>H</i>‐pyrrol‐1‐yl)thiophene‐2‐carbonitriles,"An simple and expedient approach to highly functionalized tetrasubstituted thiophenes from readily accessible starting materials [(1 H ‐pyrrol‐1‐yl)allene, isothiocyanates, and alkyl 2‐bromoacetates or 2‐bromoacetonitrile] has been developed. The method is based on the one‐pot synthesis and fast in‐situ cyclization of alkyl 2‐{[2‐(1 H ‐pyrrol‐1‐yl)buta‐2,3‐dienimidoyl]sulfanyl}acetates or cyanomethyl 2‐(1 H ‐pyrrol‐1‐yl)buta‐2,3‐dienimidothioates (1‐aza‐1,3,4‐trienes) to give previously unknown thiophene‐2‐carboxylates and thiophene‐2‐carbonitriles, respectively, both bearing pyrrole substituents.",10.1002/ejoc.201800268,2018-02-21,0.5806264515974203
Journal of the American Chemical Society,Toward the Development of a General Chiral Auxiliary. Enantioselective Alkylation and a New Catalytic Asymmetric Addition of Silyloxyfurans:  Application to a Total Synthesis of (−)-Rasfonin,"An enantioselective total synthesis of the apoptosis-inducing natural product, (-)-rasfonin, is described. Camphor lactam-mediated asymmetric alkylation reactions enabled the installation of three stereogenic centers with >95:5 diastereoselectivity. A modified Corey-Peterson olefination was employed in the construction of the (E,E)-diene system. A highly diastereoselective, asymmetric vinylogous Mukaiyama aldol addition was conducted using a chiral cationic oxazaborolidine catalyst. The pyranone core of the natural product was prepared via a DBU-promoted rearrangement of a furanol to its corresponding pyranol with concomitant [1,4]-silyl transfer.",10.1021/ja063532+,2006-08-01,0.5806257059415281
Journal of Organic Chemistry,Synthesis of Branched Trehalose Glycolipids and Their Mincle Agonist Activity,"The macrophage inducible C-type lectin (Mincle) is a pattern recognition receptor that recognizes trehalose dimycolate (TDM), and trehalose dibehenate (TDB) and related trehalose diesters, and thus represents a promising target for the development of vaccine adjuvants based on the trehalose glycolipid scaffold. To this end, we report on the synthesis of a series of long-chain α-branched, β-modified trehalose monoesters and diesters to explore how glycolipid structure affects signaling through Mincle. Key steps in our synthetic strategy include a Fráter-Seebach α-alkylation to install the C 20 aliphatic lipid on a malic acid derivative, and the formation of a β,γ-epoxide as an intermediate from which modifications to the β-position of the lipid can be made. Biological evaluation of the derivatives using nuclear factor of activated T cells (NFAT)-green fluorescent protein (GFP) reporter cell lines expressing mMincle or hMincle revealed that the hMincle agonist activity of all diesters was superior to that of the current lead trehalose glycolipid adjuvant TDB, while the activity of several monoesters was similar to that of their diester counterparts for mMincle, but all showed reduced hMincle agonist activity. Taken together, diesters 2d – g are thus potent Mincle agonists and promising vaccine adjuvants.",10.1021/acs.joc.7b03269,2018-05-21,0.5806247679931904
Organic Letters,"Copper-Catalyzed Cycloisomerization of Unactivated Allene-Tethered <i>O</i>-Propargyl Oximes: A Domino Reaction Sequence toward the Synthesis of Hexahydropyrrolo[3,4-<i>b</i>]azepin-5(4<i>H</i>)-ones","A novel copper-catalyzed cycloisomerization of unactivated allene-tethered O- propargyl oximes has been developed for the synthesis of hexahydropyrrolo[3,4- b ]azepin-5(4 H )-ones. This one-pot domino reaction proceeds via a [2,3]-sigmatropic rearrangement, a [3 + 2] cycloaddition, and another [3,3]-sigmatropic rearrangement. The methodology offers a practical and straightforward route for the rapid assembly of both ring components of the fused bicyclic motifs from acyclic precursors by simultaneously forming four new bonds (a C═O, a C═N, and two C–C bonds) in a single step.",10.1021/acs.orglett.1c00837,2021-04-12,0.580622804343013
Organic Process Research & Development,An Improved Synthesis of Amantadine Hydrochloride,"Amantadine hydrochloride 1 is an antiviral drug used in the prevention and treatment of influenza A infections. It has also been used for alleviating early symptoms of Parkinson’s disease. Several methods for the preparation of 1 have been reported. These procedures started with adamantane 2 using as many as four reaction steps to produce amantadine hydrochloride with overall yields ranging from 45% to 58%. In this article, we describe a two-step procedure for the synthesis of 1 from 2 via N -(1-adamantyl)acetamide 4 with an improved overall yield of 67%. The procedure was also optimized to reduce the use of toxic solvents and reagents, rendering it more environment-friendly. The procedure can be considered as suitable for large-scale production of amantadine hydrochloride. The structure of amantadine hydrochloride was confirmed by 1 H NMR, 13 C NMR, IR, and MS.",10.1021/acs.oprd.7b00242,2017-09-28,0.580620952328495
Organic Letters,Progress toward the Total Synthesis of Bafilomycin A<sub>1</sub>:  Stereoselective Synthesis of the C15−C25 Subunit by Additions of Nonracemic Allenylzinc Reagents to Aldehydes,[reaction: see text] A highly stereoselective synthesis of the C15-C25 subunit (2) of bafilomycin A(1) (1) has been accomplished by a route utilizing additions of chiral nonracemic allenylzinc reagents to aldehydes.,10.1021/ol006344b,2000-08-10,0.580616804764056
Journal of Organic Chemistry,Total Syntheses of (±)-Axamide-1 and (±)-Axisonitrile-1 via 6-<i>Exo-dig</i> Radical Cyclization,"Total syntheses of (+/-)-axamide-1 (1) and (+/-)-axisonitrile-1 (2) were accomplished by using the alpha-carbonyl radical cyclization as the key step. Thienylcyanocuprate 24 mediated conjugated addition of 5-(trimethylsilyl)-4-pentynylmagnesium chloride (23) to 3-methylcyclopenten-1-one (22) and subsequent treatment with TMSCl afforded silyl enol ether 25. Iodination of 25 with NaI and m-CPBA afforded alpha-iodoketone 21. 6-Exo-dig radical cyclization of 21 and subsequent desilylation furnished hydroindane derivative 20. Bicyclic ketone 20 was converted to nitrile 19 via a three-step sequence involving Luche reduction, mesylation, and S(N)2 substitution reaction. Finally, tandem alkylation-reduction on nitrile 19 and subsequent functional group transformations afforded (+/-)-axamide-1 (1) and (+/-)-axisonitrile-1 (2).",10.1021/jo802672t,2009-01-27,0.5806149051030494
Journal of the American Chemical Society,[5 + 1] Annulation:  A Synthetic Strategy for Highly Substituted Phenols and Cyclohexenones,A novel [5 + 1] annulation strategy is developed for the synthesis of highly substituted phenols and cyclohexenones from alpha-alkenoyl ketenedithioacetals and nitroalkanes.,10.1021/ja043023c,2005-03-09,0.5806147601237587
Tetrahedron,Calyculins. Asymmetric synthesis of the C26-C32 fragment,,10.1016/0040-4039(94)85330-4,1994-10-01,0.5806143775131493
Tetrahedron,Asymmetric synthesis of the C-3/C-9 fragment of (−) aspicilin,,10.1016/s0040-4039(00)79481-0,1991-01-01,0.5806143775131493
Tetrahedron,Asymmetric synthesis of a C1C19 fragment of ulapualide A,,10.1016/s0040-4039(02)01553-8,2002-09-01,0.5806143775131493
Synlett,"The First Facile Synthesis of Some 1,2a,3,8b-Tetrahydro-2H-Cyclobuta[c] Chromenes Through Intramolecular Alkylation of an Aromatic Ring by a Cyclobutanone",Starting from cyclobutanones several new chromenes containing a cyclobutane ring are prepared. Ring fission of these derivatives gives easy access to functionalized 3-isoflavenes.,10.1055/s-2002-25355,2002-01-01,0.5806127435597431
Tetrahedron,Confirmation by total synthesis of the revised structure of sporol: an application of cyclic thionocarbonate-initiated radical cyclization,The revised structure of sporol is confirmed by the synthesis of the racemate. Tri-n-butylstannyl radical induced fragmentation of a thionocarbonate and subsequent cyclization is employed to prepare a key component in the synthesis.,10.1016/s0040-4039(00)79828-5,1992-05-01,0.5806011764411708
Journal of Organic Chemistry,Novel Syntheses of Cis and Trans Isomers of Combretastatin A-4,"A high-yielding, two-step stereoselective synthesis of the anticancer drug (Z)-combretastatin A-4 (1) has been devised. The method uses the Perkin condensation of 3,4,5-trimethoxyphenylacetic acid and 3-hydroxy-4-methoxybenzaldehyde followed by decarboxylation of the cinnamic acid intermediate using copper and quinoline. The iodine-catalyzed isomerization of the Z isomer 1 results in complete conversion to the E isomer. The Suzuki cross-coupling of an aryl boronic acid and vinyl bromide has also been successfully employed to produce both Z and E isomers of combretastatin A-4 stereoselectively. Both methods are far superior to the current five-step Wittig synthesis in which both isomers are produced nonstereoselectively.",10.1021/jo015959z,2001-11-01,0.5806008655692216
Synlett,"Novel Preparation of 1,1-Dioxo-7α-methoxy-3-methyl-Δ<sup>3</sup>-cephem-4-yl Aryl Ketones","All articles of this category 1,1-Dioxo-7α-methoxy-3-methyl-Δ 3 -cephem-4-yl phenyl ketone, a valuable precursor of potent HLE inhibitors, was obtained in an efficient way starting from 7α-methoxy-3-methyl-Δ 3 -cephem-4-carboxylic acid. By employing the same methodology a variety of 1,1-dioxocephem-4-yl aryl ketones were prepared. cephems - 1,1-dioxocephem aryl ketones - acylation - decarboxylation - protease inhibitors",10.1055/s-1998-1620,1998-03-01,0.5805975707034091
Organic Process Research & Development,"Synthesis of 2-Methyl-2,5-diazabicyclo[2.2.1]heptane, Side Chain to Danofloxacin","Various syntheses of the side chain of the quinolone antibiotic danofloxacin are described. The realization that the N -methyl substitution on the side chain 2-methyl-2,5-diazabicyclo[2.2.1]heptane can reside on either nitrogen, due to the symmetry of the molecule, played a major role in the design of the commercial synthetic route.",10.1021/op8002618,2009-03-03,0.5805943372541665
Tetrahedron,"Cationic cyclization of α,β-unsaturated ketones. A facile synthesis of 9-methyldecalin-2-ol-5-one, an intermediate for synthesis of eudesmane sesquiterpenoids",,10.1016/s0040-4039(01)83229-9,1977-01-01,0.5805935678312124
Angewandte Chemie International Edition,Synthesis of the Carbocyclic Core of Zoanthenol: Implementation of an Unusual Acid-Catalyzed Cyclization,"A smokin' hot cyclization! When the racemic cyclization precursor is heated in neat trifluoroacetic acid, an unusual Friedel–Crafts-type cyclization forms the carbocyclic core of the marine alkaloid zoanthenol containing two all-carbon-substituted quaternary centers. Catalytic asymmetric alkylation allows entry into an enantioselective route.",10.1002/anie.200700430,2007-04-19,0.5805919186513196
Journal of Organic Chemistry,First Total Synthesis of Acerogenin C and Aceroside IV,"Strategically positioned arom. rings could switch the polyhydrocarbon chain from its normal extended conformation into folded one by the principle of intramol. recognition phenomena, favoring thus the intramol. reaction if these two arom. rings are correctly functionalized. Based on this conception, a new strategy for the synthesis of macrocyclic diarylheptanoids has been developed and convergent total syntheses of acerogenin C (I) (R = H) (II) and aceroside IV (I) (R = beta -D-glucopyranosyl) (III) were accomplished. Cycloetherification of linear diarylheptanoid: 1-(4-fluoro-3-nitrophenyl)-7-(3-hydroxy-4-methoxyphenyl)-heptan-3-one under mild conditions (CsF, DMF, rt) gave the macrocycle: 4-methoxy-17-nitro-2-oxa-tricyclo (13,2,23,7) eicosa-1(18),3,5,7(20),15(19),16-hexaen-12-one in 95% yield. Removal of nitro group followed by O-demethylation gave II. Glucosidation of II followed by sapon. give III in excellent overall yield. [on SciFinder (R)]",10.1021/jo9714324,1997-10-01,0.5805907905850589
Organic Letters,Synthetic Study of Azaspiracid-1:  Synthesis of the EFGHI-Ring Fragment,"Here, we report a synthesis of the lower half C21-C40 fragment of the shellfish toxin, azaspiracid-1. The C28-C40 fragment was synthesized by a coupling between the C28-C35 epoxide and the C36-C40 dithioacetal anion, followed by the HI-ring spiroaminal formation. An aldehyde corresponding to the C28-C40 fragment was then coupled with the C21-C27 allylic stannane by using InCl3. Finally, the FG-ring was constructed by HF.pyridine to accomplish the synthesis of the suitably protected C21-C40 fragment.",10.1021/ol0613766,2006-08-01,0.580588825069089
Organic Letters,"Total Synthesis of Fostriecin: Via a Regio- and Stereoselective Polyene Hydration, Oxidation, and Hydroboration Sequence","A total synthesis of the fostriecin has been achieved in 24 steps from enyne 11. The lactone moiety was installed by a Leighton allylation and Grubbs ring-closing metathesis reaction. The highly reactive Z,Z,E-triene moiety was installed via a late-stage Suzuki-Miyaura cross-coupling of a remarkably stable Z-vinyl boronate. The relative and absolute stereocenters of the C-8,9,11 triol were generated with a regio- and stereoselective asymmetric hydration/oxidation sequence.",10.1021/ol101340n,2010-08-05,0.5805848428118939
Synthesis,The Sodium/Ammonia Reduction of 5-Ethoxycarbonyl-4-methylimidazole: A Key Intermediate in the Synthesis of Cimetidine,Reduction du compose du titre en methyl-4 imidazolemethanol-5; application de cette reaction au benzimidazolecarboxylate-2 d'ethyle,10.1055/s-1984-30845,1984-01-01,0.5805817589065932
Journal of the American Chemical Society,Ruthenium-Catalyzed Alkene-Alkyne Coupling:  Synthesis of the Proposed Structure of Amphidinolide A,"The ruthenium-catalyzed alkene-alkyne coupling provides a powerful method for the synthesis of 1,4 dienes and a way to simplify synthetic strategy. The latter potential is explored in the context of a synthesis of the assigned structure of amphidinolide A, which also raises the question of the applicability of this reaction for macrocyclizations. Employing this reaction allows simplification of the target to three subunits corresponding to C-1 to C-6, C-7 to C-15, and C-16 to C-25. The C-7 to C-15 subunit involves introduction of chirality by an asymmetric dihydroxylation. The route to the C-16 to C-25 subunit introduces chirality by a Pd-catalyzed asymmetric allylic alkylation and an asymmetric epoxidation. Assembly of the three subunits employs the Ru-catalyzed addition inter- and intramolecularly. The synthesis culminated in the formation of the assigned structure and is identical to the synthetic samples prepared independently by two completely different routes. As noted by the other two groups, this structure appears to be a diastereomer of the natural product. Because this synthesis introduces all of the stereochemistry of the subunits by catalytic asymmetric processes, either enantiomer as well as diastereomers can be readily accessed to define the correct structure. Notably, the Ru-catalyzed macrocyclization to this macrolide proceeded in better yields than either a Pd-catalyzed cross-coupling or a Ru-catalyzed metathesis, macrocylization methods for the other two total synthesis.",10.1021/ja027883+,2002-09-27,0.5805645192833554
Organic Letters,Stereocontrolled Total Synthesis of (−)-Kainic Acid,"[reaction: see text] A stereocontrolled total synthesis of (-)-kainic acid is described. A fully functionalized trisubstituted pyrrolidine ring was constructed by ring-closing metathesis of an acrylate derivative followed by an intramolecular Michael addition of the resultant alpha,beta-unsaturated lactone with high diastereoselectivity. Two alternative protocols for the construction of the alpha,beta-unsaturated lactone were also developed.",10.1021/ol0631197,2007-03-30,0.5805641764876126
Journal of Organic Chemistry,"Synthetic β-1,2-Mannosyloxymannitol Glycolipid from the Fungus <i>Malassezia pachydermatis</i> Signals through Human Mincle","Mincle is a C-type lectin receptor of the innate immune system with the ability to sense pathogens and commensals through lipidic metabolites. While a growing number of bacterial glycolipids have been discovered that can signal through human Mincle, no fungal metabolites are known that can signal through the human form of this receptor. We report the total synthesis of a complex β-1,2-mannosyloxymannitol glycolipid from Malassezia pachydermatis 44-2, which was reported to signal through the murine Mincle receptor. Assembly of 44-2 was achieved through a highly convergent route that exploits symmetry elements inherent within this molecule and delineation of conditions that maintain the delicate l-mannitol triester-triol array. We show that 44-2 is a potent agonist of human Mincle signaling and constitutes the first fungal metabolite identified that can signal through the human Mincle receptor, providing new insights into antifungal immunity.",10.1021/acs.joc.9b00544,2019-05-03,0.5805624782890954
Organic Letters,Synthesis of the A–D Ring System of the Gambieric Acids,The A-D fragment of gambieric acids A and C has been synthesized using an asymmetric Tsuji-Trost allylation reaction to couple the two key segments. The A ring fragment has been prepared by a short and highly efficient route involving diastereoselective Lewis acid mediated alkylation of an acetal. Iterative ring-closing metathesis reactions have been used to construct cyclic ethers and assemble the tricyclic B-D fragment.,10.1021/acs.orglett.5b02093,2015-09-14,0.5805610054245487
Synlett,"Multigram Synthesis of 4,4-Disubstituted 3-Oxopyrrolidones: Efficient Starting Materials for Diverse 3-Functionalized Pyrrolidones","Abstract The practical, rapid development of chemical leads for drug discovery depends strongly on scalable building block synthesis procedures. N-Heterocyclic moieties, especially unsaturated ones, remain essential tools in the hands of screening and medicinal chemists. Here, we report four novel chemical block families and the interconversions between them. The synthesis of 4,4-disubstituted 3-oxopyrrolidones was an essential milestone in the diversity-oriented production of 3-aminopyrrolidones, 3-hydroxypyrrolidones, and 3,3′-difluoropyrrolidines. These compounds can be functionalized with conformationally flexible spirocyclic substituents. We developed a multigram procedure to access 4,4-disubstituted 3-oxopyrrolidones from commercially accessible and cost-saving reagents via a short three-step procedure. Here, we report the robust conversion of 3-oxopyrrolidones into 3-aminopyrrolidones, 3,3′-difluoropyrrolidones, and 3-hydroxypyrrolidones, involving a minimal number of steps. We demonstrate the scope and limitations and further perspectives for such synthetic approaches.",10.1055/a-2320-8362,2024-05-06,0.5805591287377871
Chemical Science,Enantioselective total synthesis of the unnatural enantiomer of quinine,"A practical enantioselective total synthesis of the unnatural (+)-quinine and (−)-9- <italic>epi</italic> -quinine enantiomers, which are important organocatalysts, is reported.",10.1039/c9sc03879e,2019-01-01,0.5805579797901173
Tetrahedron,A novel displacement route to P-chiral phosphine oxides of high enantiomeric purity,,10.1016/s0040-4039(00)73428-9,1994-08-01,0.5805502735872423
Tetrahedron,Three-step synthesis of 4-(2′-hydroxyethyl) azetidin-2-one and its substituted derivatives from 4-acetoxy-2-pyridones,,10.1016/s0040-4039(01)90019-x,1984-01-01,0.5805473435439077
Organic Letters,<scp>l</scp>-Fucose from Vitamin C with Only Acetonide Protection,Addition of human milk oligosaccharides (HMO) to baby foods may protect infants from disease. As many simple HMOs are fucosylated this is likely to increase the demand for L-fucose as a synthetic building block. Any chemical synthesis must be cheap to compete with a biotechnological process. Acetonide is the only protecting group we have used in this new synthesis of L-fucose from vitamin C in 27% overall yield (purification by recrystallization; no chromatography required in the entire sequence).,10.1021/ol502733x,2014-10-13,0.5805451798208096
Tetrahedron,Synthetic study of marine macrolide swinholide A. stereocontrolled synthesis of the C11 - C23 segment,,10.1016/0040-4039(94)88288-6,1994-10-01,0.5805397156990817
Tetrahedron,Synthetic study of aquayamycin. Part 1: Synthesis of 3-(phenylsulfonyl)phthalides possessing a β-C-olivoside,,10.1016/s0040-4039(00)01478-7,2000-10-01,0.5805397156990817
Organic Process Research & Development,Synthesis of Enantiopure Fmoc-α-Methylvaline,"An efficient synthesis of enantiopure Fmoc-α-methylvaline has been developed. The racemate was prepared in two steps from 3-methyl-2-butanone and was resolved using a chiral amine, ( S )-1,2,3,4-tetrahydro-1-naphthylamine to give the desired, enantiopure S -isomer in 23% overall yield.",10.1021/op700286u,2008-02-27,0.5805397058982543
Organic Letters,Synthesis of the I–K Fused Polyether Array of CTX3C and Related Ciguatoxins by Use of a Gold-Catalyzed Cyclization Reaction,The I-K fragment (C31-C49) of the ciguatoxin CTX3C has been synthesized from a simple chiral pool derived tetrahydropyranyl alcohol. An efficient gold-catalyzed cyclization reaction of a γ'-hydroxy ynone has been used to accomplish efficient closure of ring K under mild conditions. The resulting vinylogous ester has been elaborated to give a complete tricyclic fragment bearing the dimethyl-substituted side chain required for assembly of the LM spirocyclic acetal portion of the target.,10.1021/acs.orglett.3c03782,2024-01-18,0.5805381832982991
Tetrahedron,Efficient regioselective syntheses of α and β cuparenones. A new approach for the construction of the cyclopentane ring,,10.1016/s0040-4039(00)85608-7,1982-01-01,0.5805323953275043
Journal of Organic Chemistry,Stereospecific Synthesis of Functionalized Ether Phospholipids,"A new stereospecific synthesis of functionalized alkyl ether phospholipids is reported. The synthesis is based upon the following: (1) the use of ( R )-glycidyl tosylate as a chiral glycerol precursor; (2) the opening of a boron trifluoride catalyzed epoxide ring to introduce the functionalized sn -1-alkyl substituents; (3) the role of tetrahydropyranyl in protecting the sn -2-glycerol position; and (4) the elaboration of the sn -3-carbinol function, via the base hydrolysis of the acetoxy intermediate, obtained from the displacement of the toluenesulfonyl group of the substrate in dipolar aprotic media. Phosphorylation, using two different methods, has led to the development of two major classes of alkyllysophospholipids. For preparation of “modulator-phospholipid” analogues, the substituted glycerol is coupled with 2,2,2-trichloro- tert -butyl phosphodichloridite and an N-protected amino acid ester, while elaboration of the phosphocholine headgroup of the target platelet-activating factor (PAF) analogues is achieved via the 2-chloro-2-oxo-1,3,2-dioxaphospholane/trimethylamine sequence. The synthesis provides rapid and efficient access to both types of phospholipids: (1) construction of the functionalized/substituted glycerol skeleton is achieved in a straightforward four-step sequence in better than 50% overall yield, and (2) phosphitylation or phosphorylation of the respective glycerol intermediates relies on reagents that require minimal use of protecting groups. The phospholipid compounds prepared include (1) the first synthetic analogue exhibiting modulator activity in conjunction with the glucocorticoid-receptor complex and (2) an sn -1-(ω-amino)alkyl derivative of PAF, suitable for introduction of chain-terminal spectroscopic labels for biological and physicochemical studies to elucidate the mechanism of action of this highly potent alkyl ether phospholipid. The synthetic methods described herein have a great deal of flexibility, thus providing convenient general routes to a wide range of alkyl ether phospholipids.",10.1021/jo990739v,1999-11-24,0.580527473694571
Organic Letters,Total Synthesis of Ionomycin Using Ring-Opening Strategies,"[structure: see text] The total synthesis of the polyether antibiotic ionomycin, a calcium ionophore, is described. The synthesis demonstrates the utility of ring-opening methodologies as applied to the synthesis of polypropionate and deoxypolypropionate subunits, which are found in two of the four fragments in the synthesis.",10.1021/ol025872f,2002-05-01,0.5805274109009031
Synthesis,Synthesis of β-Aminocyclohexanones and β-Aminocyclohexanols through an Intramolecular Tandem Isomerization-Mannich Reaction as a Key Step,"New β-aminocyclohexanones and β-aminocyclohexanols, with a primary amino group, have been obtained by a short and efficient sequence involving an intramolecular tandem isomerization-Mannich reaction as the key step. This methodology takes advantage of tert-butanesulfinyl protection of the nitrogen atom.",10.1055/s-0030-1260195,2011-09-01,0.5805245233017151
Journal of Organic Chemistry,2-Piperidone Type of Chiral Building Block for 3-Piperidinol Alkaloid Synthesis,"An enantiomeric pair of a new 2-piperidone type of chiral building block (1) has been prepared by bakers' yeast reduction of beta-keto ester (2) or lipase-mediated transesterification of hydroxy ester (+/-)-(1), derived from NaBH(4) reduction of 2, in enantiopure form. The absolute stereochemistry of (-)-1 was verified by its conversion to known piperidine (-)-3, an intermediate for the synthesis of (-)-spectaline. The 2-piperidone (-)-1 was converted to all four diastereomers of 2,6-disubstituted 3-piperidinol chiral building blocks on the basis of homologation of (-)-1 at the lactam carbonyl using the Eschenmoser method via corresponding thiolactams (-)-9, (-)-20, (-)-25, (-)-27, and (-)-34, followed by stereocontrolled reduction of the resulting vinylogous urethanes (+)-10, (+)-15, (+)-23, (+)-28, and (+)-32, respectively, and epimerization of the hydroxyls at the 3-position [(-)-16 via (+)-17 to (-)-18 and (+)-29 via (+)-30 to (+)-31]. The versatility of these chiral buliding blocks has been demonstrated by the chiral synthesis of the 3-piperidinol alkaloids (+)-prosafrinine, (-)-iso-6-cassine, (-)-prosophylline, and (-)-prosopinine from (-)-37, (-)-14, (+)-36, and (-)-26, respectively.",10.1021/jo990397t,1999-06-01,0.58052259852077
Tetrahedron,Stereoselective alkylation of chiral glycine enolate synthons. The enantioselective synthesis of α-amino acid derivatives.,,10.1016/s0040-4039(00)82269-8,1988-01-01,0.580521028601345
Tetrahedron,Highly diastereoselective bis-hydroxylation of the amino-deoxy-conduritol C ring system. A formal synthesis of the aminocyclitol moiety of the antibiotic Hygromycin A,,10.1016/0040-4039(94)02465-n,1995-02-01,0.5805170718465132
Organic Letters,Alternative One-Pot Synthesis of (Trifluoromethyl)phenyldiazirines from Tosyloxime Derivatives: Application for New Synthesis of Optically Pure Diazirinylphenylalanines for Photoaffinity Labeling,"Alternative one-pot synthesis of 3-(trifluoromethyl)-3-phenyldiazirine derivatives from corresponding tosyloximes is developed. The deprotonation of intermediate diaziridine by NH2(-) is a new approach for construction of diazirine. Moreover, a novel synthesis of optically pure (trifluoromethyl)diazirinylphenylalanine derivatives was attempted involving these methods.",10.1021/ol503630z,2015-01-14,0.5805152384824641
Organic Letters,"Stereodivergent Total Synthesis of Hapalindoles, Fischerindoles, Hapalonamide H, and Ambiguine H Alkaloids by Developing a Biomimetic, Redox-Neutral, Cascade Prins-Type Cyclization","A stereoselective, redox-neutral, Brønsted acid-catalyzed cascade Prins-type cyclization between indole and aldehyde is described to access several structurally diverse indole terpenoid scaffolds in a single step. Applying this concept, stereodivergent total syntheses of nine hapalindole-type alkaloids are accomplished. Key transformations include allylation using geometrically isomeric allylboronic acid followed by a p-toluenesulfonic acid mediated deprotection-cyclization cascade.",10.1021/acs.orglett.8b02804,2018-10-11,0.580515004024996
Tetrahedron,"Synthesis of a novel bridged nucleoside bearing a fused-azetidine ring, 3′-amino-3′,4′-BNA monomer",,10.1016/s0040-4039(03)01279-6,2003-06-30,0.5805104889318381
Synthesis,2-Carbamimidoylbenzoic Acid as a New Effective and Available Precursor for the Synthesis of Substituted 2-(Pyrimidin-2-yl)benzoic Acids,"Abstract A new approach to the synthesis of 2-(pyrimidin-2-yl)benzoic acids based on the ring contraction of the 2-carbamimidoylbenzoic acid [(2-amidinobenzoic) acid] with 1,3-dicarbonyl compounds and their synthetic equivalents has been developed. The intramolecular condensation of the obtained acids with 1,3-dielectrophiles proceeds with the formation of the 4,6-dihydropyrimido[2,1-a]isoindole-4,6-dione system, the pyrrolidone ring of which is easily opened under the action of weak nucleophiles. The reaction of 2-amidinobenzoic acid with chromones, which have an aryloxy group at 3-position does not stop at the step of pyrimidine ring formation and undergoes further spontaneous cyclization into 2-(benzo[4,5]furo[3,2-d]pyrimidin-2-yl)benzoic acids.",10.1055/s-0040-1705941,2020-11-16,0.5805103354611475
Journal of Organic Chemistry,Cobalt-Catalyzed Hartung–Mukaiyama Cyclization of γ-Hydroxy Olefins: Stereocontrolled Synthesis of the Tetrahydrofuran Moiety of Amphidinolide N,"Cobalt-catalyzed Mukaiyama-type cyclization of γ-hydroxy olefins is known as an atom- and step-economical means for stereoselective synthesis of 2,5- trans -substituted tetrahydrofuran derivatives. In this study, we investigated the synthesis of a series of 2,5-substituted tetrahydrofuran derivatives by means of a cobalt-catalyzed Hartung–Mukaiyama cyclization. The stereochemical consequence of the reaction was found to be largely dependent on the substitution pattern and relative configuration of γ-hydroxy olefins. 2,5- cis -Substituted tetrahydrofuran derivatives could be obtained diastereoselectively from appropriately substituted γ-hydroxy olefins. Additionally, relatively bulky olefin substituents and unprotected hydroxy groups at non-interfering positions (e.g., α and δ) were well tolerated in the reaction. Finally, the synthetic versatility of the Hartung–Mukaiyama cyclization was demonstrated through a stereocontrolled synthesis of the tetrahydrofuran moiety of amphidinolide N, a potent cytotoxic macrolide of marine origin. This study expands the capacity of Mukaiyama-type cyclization in that it can be used in convergent assembly of complex tetrahydrofuran motifs from internal olefins.",10.1021/acs.joc.1c00085,2021-03-26,0.5805033291255128
Tetrahedron,Asymmetric palladium annulation: formal synthesis of (+)-huperzine A,,10.1016/s0040-4039(99)01874-2,1999-12-01,0.5805028818767142
Tetrahedron,"Synthetic studies on bryostatins, antineoplastic metabolites: Convergent synthesis of the C1-C16 fragment shared by all of the bryostatin family",,10.1016/s0040-4039(00)74063-9,1993-07-01,0.5804974237795864
European Journal of Organic Chemistry,Chemical Synthesis and Proinflammatory Responses of Monophosphoryl Lipid A Adjuvant Candidates,"Lipopolysaccharides (LPS), which are structural components of the outer surface membrane of Gram-negative bacteria, trigger innate immune responses through activation of Toll-like receptor 4 (TLR4). Such responses may be exploited for the development of adjuvants and in particular monophosphoryl lipid A (MPLA) obtained by controlled hydrolysis of LPS of Salmonella minnesota, exhibits low toxicity yet possesses beneficial immuno-stimulatory properties. We have developed an efficient synthetic approach for the preparation of a major component of MPLA (1), which has as a key feature the use of allyloxycarbonates (Alloc) as permanent protecting groups for the C-3 and C-4 hydroxyls of the proximal glucosamine unit. The latter protecting groups greatly facilitated deprotection of the fully assembled compound. Furthermore, the amino functions were protected as N-2,2,2-trichloroethoxycarbamates (Troc), which performed efficient neighboring group participation to give selectively 1,2-trans-glycosides and could easily be removed under mild conditions without affecting the permanent Alloc carbonates and anomeric dimethylthexylsilyl (TDS) ether. The synthetic methodology was also employed for the preparation of a monophosphoryl lipid A (2) derivative that has the anomeric center of the proximal sugar modified as a methyl glycoside. Compound 1 was not able to induce cytokine production in mouse macrophages whereas methyl glycoside 2 displayed activity, however it has a lower potency and efficacy than lipid A obtained by controlled hydrolysis S. minnesota. This indicates compound 2 is an attractive candidate for adjuvant development and that 1 is not the active substance of MPLA obtained by controlled hydrolysis of LPS.",10.1002/ejoc.200900973,2009-11-18,0.5804932231092713
Synlett,"Synthesis of Pyrimidine 1′,3′-Anhydro-β-<scp>d</scp>-<i>psico</i>- and -<i>sorbo</i>-furanosyl Nucleosides","A novel approach for the synthesis of pyrimidine 1′,3′-anhydro-β-d-psico- and -sorbo-furanosyl nucleosides 2 and 3, ­respectively, has been developed. The approach described here ­employs a readily available O 2,3′-anhydro-β-d-fructofuranosyl­uracil (1) as a key starting compound.",10.1055/s-2005-871547,2005-01-01,0.5804925704144163
Tetrahedron,"An efficient synthesis of 4,5-dihydronaphtho[2,1-b]furan through a novel ring transformation of 2H-pyran-2-one",,10.1016/j.tetlet.2004.10.011,2004-10-30,0.5804897849413027
Synthesis,A Convenient Synthesis of Ethyl 3-Aminopropanedithioate (β-Alanine Ethyl Dithioester),All articles of this category A five-step sequence allowing the preparation of ethyl 3-aminopropanedithioate from N -(Boc)-β-alanine via the key intermediate N -(Boc)- β -alaninethioacyl- N -phthalimide is described. dithioester - thioacyl- N -phthalimide,10.1055/s-1999-3417,1999-03-01,0.5804893119001558
Organic Letters,"Expedient Synthesis of Pyrrolo[1,2-<i>a</i>]indoles: Preparation of the Core of Yuremamine","Pyrrolo[1,2- a]indoles are conveniently prepared from tetrahydro-1,2-oxazines, which in turn are generated through the reaction of nitrones with 1,1-cyclopropanediesters. The synthetic route proves to be highly diastereoselective and provides access to the core of the recently discovered pyrrolo[1,2- a]indole natural product yuremamine.",10.1021/ol8012777,2008-07-11,0.5804885838959903
Organic Process Research & Development,Development and Scale-up of an Organocatalytic Enantioselective Process to Manufacture (<i>S</i>)-Pregabalin,"Herein is reported the development of a new process to manufacture ( S )-pregabalin. The method comprises six steps, run under the catalysis of a recyclable polymer bound phase transfer catalyst, and afforded ( S )-pregabalin in overall 54% yield, starting from building blocks acetylacetone, isovaleraldehyde, and nitromethane.",10.1021/acs.oprd.5b00160,2015-08-05,0.5804880758013005
Synthesis,New Applications of PhI(OAc)2 in Synthesis: Total Synthesis and SAR Development of Potent Antitumor Natural Product Psymberin/Irciniastatin A,"A novel PhI(OAc)2-mediated oxidative cyclization reaction is discovered for the synthesis of α-oxy N-acyl aminals and hemiaminals in good yields from readily synthesized N-acyl enamines. This methodology represents a cascade process to construct the core structure of the pederin family of natural products. The total synthesis of psymberin, a member of the pederin family, is accomplished using this ring-closure reaction as the key step. This new method is further showcased in the preparation of advanced psymberin analogues. The biological data of these analogues are presented.",10.1055/s-0029-1216926,2009-08-07,0.5804830189128382
Journal of the American Chemical Society,"Stereodivergent Construction of 3,3′-Disubstituted Oxindoles via One-Pot Sequential Allylation/Alkylation and Its Application to the Total Synthesis of Trigolute B and D","The absolute and relative configurations of bioactive chiral molecules are typically relevant to their biological properties. It is thus highly important and desirable to construct all possible stereoisomers of a lead candidate or a given bioactive natural compound. Synergistic dual catalysis has been recognized as a reliable synthetic strategy for a variety of predictable stereodivergent transformations. Despite the impressive progress made in this field, stereodivergent carbon-carbon bond-formation reactions involving stabilized nucleophiles remain elusive. Herein, we report an iridium- and magnesium-catalyzed one-pot sequential allylic alkylation/nucleophilic alkylation cascade process for the stereodivergent synthesis of all four stereoisomers of 3,3'-disubstituted oxindoles through a three-component reaction. A diverse array of products is readily prepared with high functional group compatibility in good yields with excellent diastereo- and enantioselectivities. Subsequently, the stereodivergent total synthesis of four stereoisomers of the spirooxindole alkaloid trigolutes B and D has been accomplished through a concise and unified synthetic route using the same set of starting materials.",10.1021/jacs.4c17425,2025-01-28,0.5804829624066669
Tetrahedron,Silicon in synthesis: stabase adducts - a new primary amine protecting group: alkylation of ethyl glycinate,,10.1016/s0040-4039(01)90439-3,1981-01-01,0.5804811670759253
Journal of Organic Chemistry,Total Synthesis of the Four Enantiomerically Pure Diastereomers of 8-F<sub>2t</sub>-Isoprostane,Syntheses of the four enantiomerically pure diastereomers of 8-F(2t)-isoprostane (5-8) are described. The key to this approach was to prepare the racemic alcohol 9 in high diastereomeric purity and then resolve 9 by lipase-mediated acetylation to yield the enantiomerically pure alcohols 30 and 32.,10.1021/jo001731k,2001-02-10,0.5804785237681634
Tetrahedron,A novel entry into a new class of cyclophane derivatives: synthesis of (±)-[2.2]paracyclophane-4-thiol,,10.1016/s0040-4039(00)01992-4,2001-01-01,0.580472065853292
Tetrahedron,An efficient stereoselective synthesis of (+)-deoxoprosophylline,,10.1016/j.tetlet.2007.07.034,2007-07-12,0.5804686233609363
Tetrahedron,"An efficient stereoselective synthesis of (2S,4S,5R)-(−)-bulgecinine",,10.1016/s0040-4039(01)00071-5,2001-03-01,0.5804686233609363
Tetrahedron,"An efficient stereoselective synthesis of (2S,4S,5R)-(−)- and (2R,4R,5S)-(+)-bulgecinine",,10.1016/j.tetlet.2004.11.101,2004-12-13,0.5804686233609363
Tetrahedron,"An efficient and stereoselective synthesis of 1,2-0-dialkyl-3-0-β-d-dlycosyl-sn-glycerols",,10.1016/s0040-4039(00)81621-4,1983-01-01,0.5804686233609363
Angewandte Chemie International Edition,Structure‐Guided Discovery of a Potent and Selective Cell‐Active Inhibitor of SETDB1 Tudor Domain,"Abstract SET domain bifurcated protein 1 (SETDB1) is a histone lysine methyltransferase that promotes the silencing of some tumour suppressor genes and is overexpressed in many cancers. SETDB1 contains a unique tandem tudor domain (TTD) that recognizes histone H3 sequences containing both methylated and acetylated lysines. Beginning with the identification of a hit compound ( Cpd1 ), we discovered the first potent and selective small molecule SETDB1‐TTD inhibitor ( R , R )‐59 through stepwise structure‐guided optimization. ( R , R )‐59 showed a K D value of 0.088±0.045 μM in the ITC assay. The high potency of ( R , R )‐59 was well explained by the cocrystal structure of the ( R , R )‐59 ‐TTD complex. ( R , R )‐59 is an endogenous binder competitive inhibitor. Evidence has also demonstrated its cellular target engagement. Interestingly, the enantiomer ( S , S )‐59 did not show activity in all the assays, highlighting the potential of ( R , R )‐59 as a tool compound in exploring the biological functions of SETDB1‐TTD.",10.1002/anie.202017200,2021-01-29,0.5804648072336149
Organic Letters,Total Syntheses of Cinchona Alkaloids via Photoredox-Catalyzed Deoxygenative Arylation,"Metallaphotoredox-enabled deoxygenative arylation of alcohols is a recently developed robust synthetic strategy for sp 2 –sp 3 coupling by MacMillan. Inspired by this method, we report herein its first utilization in natural product total synthesis through realizing the coupling of 4-bromo-quinoline or 4-bromo-6-methoxyquinoline with quincorine or quincoridine, respectively. The alcohols were de novo synthesized in racemic form by a key step of the intramolecular Diels–Alder reaction or in an enantioselective manner by Ir/amine dual-catalyzed allylation. All members of the cinchona alkaloids could be prepared efficiently.",10.1021/acs.orglett.3c01659,2023-06-13,0.5804590217633039
Journal of Organic Chemistry,"An S<sub>N</sub>1-type Reaction To Form the 1,2-Dioxepane Ring: Synthesis of 10,12-Peroxycalamenene","The synthesis of the sesquiterpene endoperoxide natural product 10,12-peroxycalamenene has been achieved. Featured transformations include an intramolecular Heck reaction to build the fused bicyclic core and a cobalt-catalyzed peroxidation to install the peroxide functional group. The final step involved an SN1-type ring closure catalyzed by DDQ to construct the 1,2-dioxepane ring.",10.1021/acs.joc.5b01326,2015-07-09,0.580453888617872
Journal of the American Chemical Society,"Total Syntheses of Amphidinolide T1, T3, T4, and T5","A concise, flexible, and high yielding entry into the family of amphidinolide T macrolides, a series of cytotoxic natural products of marine origin, has been developed. All individual members, except amphidinolide T3 (3), derive from compound 39 as a common synthetic intermediate which is formed from three building blocks of similar size and complexity. The fragment coupling steps involve a highly diastereoselective SnCl(4) mediated reaction of the furanosyl sulfone derivative 11 with the silyl enol ether 18 and a palladium-catalyzed Negishi type coupling reaction between the polyfunctional organozinc reagent derived from iodide 32a and the enantiopure acid chloride 24b. The 19-membered macrocyclic ring is then formed by a high yielding ring closing metathesis (RCM) reaction of diene 33 catalyzed by the ""second generation"" ruthenium carbene complex 34. The efficiency of the RCM transformation stems, to a large extent, from the conformational bias introduced by the syn-syn-configured stereotriad at C12-C14 of the substrate which constitutes a key design element of the synthesis plan. The use of Nysted's reagent 38 in combination with TiCl(4) was required for the olefination of the sterically hindered ketone group in 36, whereas more conventional alkene formations were unsuccessful for this elaboration. Finally, it is shown that the inversion of a single and seemingly remote stereocenter (C12) in one of the building blocks not only affects the efficiency and stereochemical outcome of the RCM step but also exerts a significant influence on the course of the acyl-Negishi reaction, allowing a radical manifold to compete with productive cross coupling.",10.1021/ja038216z,2003-11-20,0.5804501378424434
Journal of Organic Chemistry,"Addition of Difluorocarbene to 3‘,4‘-Unsaturated Nucleosides:  Synthesis of 2‘-Deoxy Analogues with a 2-Oxabicyclo[3.1.0]hexane Framework<sup>1</sup>","Treatment of protected 2'-deoxy-3',4'-unsaturated nucleosides derived from adenosine and uridine with difluorocarbene [generated from bis(trifluoromethyl)mercury and sodium iodide] gave fused-ring 2,2-difluorocyclopropane compounds. Stereoselective alpha-face addition to the dihydrofuran ring resulted from hindrance by the protected beta-anomeric nucleobases. A protected uracil compound was converted smoothly into the cytosine derivative via a 4-(1,2,4-triazol-1-yl) intermediate. Removal of the protecting groups gave new difluorocyclopropane-fused nucleoside analogues. The solid-state conformation of the nearly planar furanosyl ring in the uracil compound had a shallow 2E pucker, and a more pronounced 1E conformation was present in the furanosyl ring of the cytosine derivative.",10.1021/jo061965p,2006-12-16,0.5804481006510442
Organic Letters,A New Approach for the Synthesis of Hyperbranched <i>N</i>-Glycan Core Structures from Locust Bean Gum,"A novel protocol for the synthesis of general N-glycan core structures was established by means of Manβ(1→4)Man peracetate derived from a naturally abundant locust bean gum as a key starting material. Phenyl (2-O-benzyl-4,6-O-benzylidine-β-D-mannopyranosyl)-(1→4)-3,6-di-O-benzyl-2-azido-2-deoxy-1-thio-β-D-glucopyranoside facilitated the synthesis of key intermediates leading to hyperbranched N-glycan core structures.",10.1021/ol403140h,2013-11-21,0.5804426847152035
Synthesis,"Chemistry of Halonitroethenes, Part 2: Trichloronitroethene as a Building Block for the Novel Synthesis of 5-Chloro(nitro)methyl-Substituted 1-Aryltetrazoles","Conversion of 1,1,2-trichloro-2-nitroethene with an excess of 1H-benzotriazole, followed by transamination of the resulting 1,1-bis(benzotriazol-1-yl)-2-chloro-2-nitroethene with different aniline derivatives provides the corresponding 1-(arylimino)-1-(benzotriazolyl)ethanes. Upon cycloaddition with sodium azide, these amidines enable the formation of hitherto unknown 1-aryltetrazoles bearing a chloro(nitro)methyl group in the 5-position. The structure of a 4-fluorophenyl derivative was proven by single-crystal X-ray diffraction analysis. Starting from arenediamines, this reaction affords bistetrazoles. In addition, the tetrazoles are interesting starting materials for further conversions of the side chain.",10.1055/s-0031-1289716,2012-02-17,0.5804423844389853
Organic Process Research & Development,"Convenient, Large-Scale Synthesis of (<i>S</i>)-TRIP Using Suzuki Cross-Coupling Conditions","A three-step synthesis of ( S )-TRIP enabled by efficient Suzuki cross-coupling conditions using commercial starting materials was developed and demonstrated on a kilogram scale. These novel Suzuki reaction conditions feature Pd 2 (dba) 3 /CataCXium A in the presence of TBAB and KOH and provide conversions up to 90% while minimizing the formation of common byproducts. Following an improved demethylation protocol and a powerful methanol purification protocol during step 2, high-quality catalyst of up to 99% purity was isolated in 52% yield over three steps.",10.1021/acs.oprd.1c00386,2022-01-10,0.5804393935616805
European Journal of Organic Chemistry,Convergent Synthesis and Diversity of Amino Acid Based Dendrimers,"The synthesis of amino acid based dendrimers 25 (fifth generation, 32 endgroups), 30 (fourth generation, 81 endgroups), chiral dendrimer 23 (third generation, 8 endgroups) as well as core-modified dendrimers 34 and 38 by the convergent method is described. The amino acid building blocks are derived from hydroxybenzoic acid derivatives and amino alcohol derivatives, and access to a considerable molecular diversity of these novel dendrimers can be achieved. The synthesis can be carried out on a relatively large scale, and this easy access of the dendrimers may lead to many potential applications.",10.1002/1099-0690(200105)2001:10<1903::aid-ejoc1903>3.0.co;2-w,2001-05-01,0.5804388330300189
Journal of the American Chemical Society,Ruthenium-Catalyzed Aldehyde Functionality Reshuffle: Selective Synthesis of<i>E</i>-2-Arylcinnamaldehydes from<i>E-</i>β-Bromostyrenes and Aryl Aldehydes,A new concept for highly selective synthesis of E-2-arylcinnamaldehydes has been developed via a formal arylformylation of E-β-bromostyrenes with readily available aryl aldehydes. This strategy involves an overall reshuffle of the aldehyde functionality with a loss of hydrogen bromide.,10.1021/ja306025d,2012-09-22,0.5804364302481777
Organic Letters,"Regioselective Cu(I)-Catalyzed Tandem A<sup>3</sup>-Coupling/Decarboxylative Coupling to 3-Amino-1,4-Enynes","An efficient and novel copper-mediated protocol for the synthesis of 3-amino-1,4-enynes from glyoxylic acid, an amine, and an alkyne was developed. This new reaction involving two sequential C-C bond formations is air and moisture tolerant and proceeds via a tandem A(3)-coupling and a selective decarboxylative coupling.",10.1021/ol3006612,2012-03-28,0.5804335968497297
Organic Letters,The Taumycin A Macrocycle: Asymmetric Total Synthesis and Revision of Relative Stereochemistry,The first asymmetric total synthesis and revision of the relative configuration of the 12-membered taumycin A macrocycle is described. Key to the success of this work was a novel α-keto ketene macrocyclization that provided an efficient means by which to access two diastereomers of the desired macrolide without the need to employ additional coupling agents or unnecessary oxidation state adjustments.,10.1021/ol5025585,2014-09-23,0.5804298480088821
Synthesis,A Useful Route to Both Enantiomers of 1-Amino-2-alkanols: Synthesis of 1-Amino- 3-methyl-2-butanol from Valine,"All articles of this category A multistep synthesis of ( S )-1-amino-3-methyl-2-butanol (9) from D-valine (3) is reported. The enantiomeric purity of ( S )- 9 (97.2 ± 0.2%percnt; ee) is determined by GC of the derivative, 5-isopropyloxazolidin-2-one (2) on both L- and D-Chirasil-Val. ( R )- 9 is prepared from L-valine in the same manner; thus, the procedure provides a useful route to both enantiomers of 1-amino-2-alkanols, starting from L- and D-amino acids, respectively.",10.1055/s-1994-25657,1994-01-01,0.5804241820703557
Tetrahedron,"Distomadines A and B, novel 6-hydroxyquinoline alkaloids from the New Zealand ascidian, Pseudodistoma aureum",,10.1016/s0040-4039(03)00831-1,2003-04-30,0.5804178456371613
Tetrahedron,"A novel neolignan, mansoxetane, and two new sesquiterpenes, mansonones R and S, from Mansonia gagei",,10.1016/s0040-4039(03)01616-2,2003-08-01,0.5804178456371613
Tetrahedron,"A novel 8,9-seco-rhamnofolane and a new rhamnofolane endoperoxide from Jatropha integerrima roots",,10.1016/s0040-4039(03)00704-4,2003-04-01,0.5804178456371613
Tetrahedron,"Yonarolide: a new marine norditerpenoid possessing a novel tricyclic skeleton, from the Okinawan soft coral of the genus, Sinularia",,10.1016/0040-4039(95)01867-h,1995-11-01,0.5804178456371613
Tetrahedron,"Three novel and one new lignan, chamaecypanones A, B, obtulignolide and isootobanone from the heartwood of Chamaecyparis obtusa var. formosana",,10.1016/s0040-4039(01)01272-2,2001-09-01,0.5804178456371613
Journal of the American Chemical Society,Enantioselective Synthesis of Planar Chiral Organonitrogen Cycles,Enantioselective synthesis of a planar chiral organonitrogen cycle has been newly developed based on the unprecedented prochiral face-selective cyclization of achiral linear precursors by an appropriate chiral promoter.,10.1021/ja1024657,2010-06-21,0.5804153258370687
Angewandte Chemie International Edition,Facile Enzymatic Synthesis of Ketoses,"Studies of rare ketoses have been hampered by a lack of efficient preparation methods. A convenient, efficient, and cost-effective platform for the facile synthesis of ketoses is described. This method enables the preparation of difficult-to-access ketopentoses and ketohexoses from common and inexpensive starting materials with high yield and purity and without the need for a tedious isomer separation step.",10.1002/anie.201505714,2015-08-14,0.580408942288389
Organic Letters,Enantioselective Total Synthesis of (+)-Gliocladin C,"The first total synthesis of gliocladin C, a fungal-derived marine alkaloid containing a rare trioxopiperazine fragment, is reported. This asymmetric synthesis establishes the absolute configuration of this structurally novel natural product. [reaction: see text].",10.1021/ol062801y,2006-12-22,0.5804088943117137
Organic Letters,Total Synthesis of Gastrodinol via Photocatalytic 6π Electrocyclization,"The first total synthesis of gastrodinol, an unprecedented poly- p -cresol-substituted natural product with a rearranged and reconstructed C ring moiety, is reported. Our synthesis features a convergent fragment approach. The Sonogashira coupling reaction forges the two segments together to furnish the conjugated ene–yne. Photocatalytic 6π electrocyclization followed by spontaneous aromatization is used to construct the tetrasubstituted B ring at the late stage. Further study shows that gastrodinol exhibits significant cytotoxic activity against five human cancer cell lines in vitro (IC 50 2.5–3.8 μM).",10.1021/acs.orglett.0c02335,2020-08-24,0.5804077282624833
Angewandte Chemie International Edition,Total Synthesis of Linoxepin through a Palladium‐Catalyzed Domino Reaction,"Convergent and elegant: Linoxepin (see picture), a new lignan with an unusual oxepin moiety, has been synthesized in only 10 steps. The protecting-group-free total synthesis includes a palladium- catalyzed Sonogashira reaction and a domino carbopalladation/Heck reaction of an allylsilane.",10.1002/anie.201209868,2013-02-12,0.5804073785141471
Synlett,Chemoenzymatic Synthesis of Ubiquitous Biological Redox Cofactors,"Redox cofactors are utilized by a myriad of proteins, ranging from metabolic enzymes to those performing post-translational modifications. Labeled redox cofactors have served as a vital tool for a broad range of studies. This account describes chemoenzymatic syntheses of the isotopically labeled, biologically important redox cofactors: nicotinamide adenine dinucleotide, methylene tetrahydrofolate, and flavin nucleotides. An overview of the general strategy is presented. These examples demonstrate the utility of enzymatic synthesis. 1 Introduction 2 Nicotinamide Cofactors 2.1 Synthesis of Remote-Labeled 14C-NADPH 2.1.1 Synthesis of [Ad-14C]NADPH 2.1.2 Synthesis of [Carbonyl-14C]NADPH 2.2 Synthesis of S- and R-[4-3H]NADPH 2.2.1 One-Step S- and Three-Step R-[4-3H]NADPH Synthesis 2.2.2 One-Pot, One-Step R-[4-3H]NADPH Synthesis 2.3 Synthesis of S- and R-[Ad-14C, 4-2H]NADPH 2.3.1 One-Step S-, Three-Step R-[Ad-14C, 4-2H]NADPH Synthesis 2.3.2 One-Pot, One-Step R-[Ad-14C, 4-2H]NADPH Synthesis 3 Methylene Tetrahydrofolate 4 Flavin Nucleotides 5 Conclusions and Outlook",10.1055/s-0036-1588768,2017-04-10,0.5803966582856975
Organic Letters,The First Total Synthesis of (±)-Cyclophostin and (±)-Cyclipostin P: Inhibitors of the Serine Hydrolases Acetyl Cholinesterase and Hormone Sensitive Lipase,"Cyclophostin, a structurally unique and potent naturally occurring acetyl cholinesterase (AChE) inhibitor, and its unnatural diastereomer were prepared in 6 steps and 15% overall yield from hydroxymethyl butyrolactone. The unnatural diastereomer of cyclophostin was converted into cyclipostin P, a potent naturally occurring hormone sensitive lipase (HSL) inhibitor, using a one pot dealkylation-alkylation process. The inhibition [IC(50)] of human AChE by cyclophostin and its diastereomer are reported, as well as constituent binding (K(I)) and reactivity (k(2)) constants.",10.1021/ol200991x,2011-05-17,0.5803962419615214
Tetrahedron,A new method for the synthesis of olefins via β-hydroxy sulfoxides,,10.1016/s0040-4039(01)84401-4,1972-01-01,0.5803811106921817
Tetrahedron,Selective mono N-alkylations of cyclen in one step syntheses,,10.1016/j.tetlet.2007.09.022,2007-09-11,0.5803787153656442
Tetrahedron,Synthesis of tetrahydroazocines and dihydro-2H-thiocins via ring enlargement,,10.1016/s0040-4039(01)87027-1,1973-01-01,0.580376451359387
Organic Letters,"Novel Synthetic Approach to 6,7-Dihydro-5<i>H</i>-imidazo[1,5-a]-pyrazin-8-ones","[reaction: see text] A novel route to highly substituted chiral 6,7-dihydro-5H-imidazo[1,5-a]pyrazine-8-ones starting from Meldrum's acid is disclosed. The key features of the methodology are the incorporation of amino esters as a chiral pool and facile mild intramolecular cyclization to form the pyrazine ring. Incorporation of various substituents at different stages of the synthesis from various building block sets makes this methodology readily amenable to parallel synthesis.",10.1021/ol035455i,2003-09-18,0.580375708116941
Tetrahedron,A practical synthesis of LFA-1 inhibitors utilizing CuCl-promoted intramolecular cyclization of thiohydantoins,,10.1016/j.tetlet.2004.11.065,2004-12-11,0.5803750041730346
Organic Letters,"Catalytic Undirected Intermolecular C–H Functionalization of Arenes with 3-Diazofuran-2,4-dione: Synthesis of 3-Aryl Tetronic Acids, Vulpinic Acid, Pinastric Acid, and Methyl Isoxerocomate","A variety of 3-aryl tetronic acids have been synthesized by an undirected, intermolecular C-H functionalization of arenes with 3-diazofuran-2,4-dione. This methodology featured as a key step in the synthesis of a series of naturally occurring 3-aryl-5-arylidene tetronic acids (pulvinates) from commercially available tetronic acid. Salient features of the pulvinic acid synthesis include a one-step, stereoselective synthesis of the C5 arylidene group and a single step introduction of the C3 aryl substituent.",10.1021/acs.orglett.6b03087,2016-11-08,0.580371086731076
Organic Letters,Diastereoselective Synthesis of Piperazines by Manganese-Mediated Reductive Cyclization,A simple and effective synthesis of trans aryl-substituted piperazines using a Brønsted acid and manganese(0) is described. [reaction: see text],10.1021/ol034469l,2003-04-08,0.5803589943492777
Journal of the American Chemical Society,Enantioselective Construction of β-Substituted γ-Lactone through Catalytic Asymmetric Oshima–Utimoto Reaction: Divergent Total Syntheses of (−)-Podophyllotoxin and Its Eleven Congeners,"We report the first highly enantioselective Oshima–Utimoto reaction, which is combined with subsequent one-pot oxidation to construct synthetically important enantioenriched β-substituted γ-lactones with high enantioselectivity (up to 97% ee) from two chemical feedstocks (allylic alcohols and vinyl ethers). Significantly, the absolute configuration of chiral β-substituted γ-lactones can be precisely controlled by strategically selecting Z - or E -allylic alcohol substrates, thereby providing an alternative access to both enantiomers of chiral γ-lactones. Capitalizing on this catalytic asymmetric transformation as a key step, we have achieved a concise and stereodivergent total synthesis of the natural aryltetralin lignan drug (−)-podophyllotoxin and its 11 structural congeners in only 6–8 steps from commercial materials through the combination of chemical and chemoenzymatic strategies. The present protocol, featuring the development of a catalytic asymmetric Oshima–Utimoto reaction, not only offers a concise route to the synthetically valuable β-substituted γ-lactones, but also establishes a potential platform for preparing structurally diverse natural drug (−)-podophyllotoxin derivatives through minor modifications of synthetic precursors.",10.1021/jacs.5c07358,2025-08-19,0.580358155849882
Synlett,Synthesis of Tricyclic Azakynurenic Acids as a New Class of NMDA-Glycine Antagonists Using Novel Stille Coupling Reaction,All articles of this category Stille coupling reaction of tosylamide 4 with tributyl(vinyl)tin gave directly tricyclic compound 5 in moderate yield. Deprotection of 5 led to novel azakynurenic acid 5a which showed affinity to the glycine binding site of the NMDA receptor. Stille reaction - NMDA-glycine antagonist - tricyclic azakynurenic acid,10.1055/s-1997-6149,1997-06-01,0.580357048215374
Tetrahedron,"Chemo- and stereoselective reduction of (pivaloyloxy)methyl 6,6-dihalopenicillanates by trineophyltin hydride: Selective synthesis of 6β-halopenicillanates",,10.1016/s0040-4039(00)99280-3,1989-01-01,0.5803441069227624
Organic Letters,Intramolecular Formal Aza-[3 + 3] Cycloaddition Approach to Indoloquinolizidine Alkaloids. A Stereoselective Total Synthesis of (±)-Tangutorine,[reaction: see text] A 19-step stereoselective total synthesis of (+/-)-tangutorine is described here. The total synthesis features an intramolecular aza-[3 + 3] formal cycloaddition strategy and also a Heck coupling for constructing the C2-C3 bond. This work provides a novel approach toward the indoloquinolizidine family of alkaloids.,10.1021/ol030114q,2003-10-29,0.580337877182644
Journal of Organic Chemistry,A Unified Strategy for the Synthesis of Diverse Bicyclo[2.2.2]octadiene Ligands,"A new approach for the enantioselective synthesis of various bicyclo[2.2.2]octadiene ligands has been developed, which features a chiral oxazaborolidinium-catalyzed asymmetric Diels–Alder reaction to construct the bicyclo[2.2.2]octane framework. The pivotal ketone 12 served as a common intermediate that was finally transformed into the desired C 1 - and C 2 -symmetric chiral dienes. This work provides an alternative method to the reported chiral diene synthesis and would be beneficial to exploration of the potentials of this type of versatile ligand in new asymmetric transformations.",10.1021/acs.joc.5c00115,2025-04-19,0.5803350430097676
European Journal of Organic Chemistry,"Synthesis of 10β,17α-Dimethyl-17β-(1,2-dioxopropyl)estra-5,9-diene-3-ketal","The synthesis of a new progestomimetic steroid, analogous to the cetaloxopromegestone precursor of Trimegestone has been carried out in eight steps from 9α-hydroxyandrost-4-ene-3,17-dione. This latter compound can be obtained from the fermentation of γ-sitosterol, a sterol extracted from soya bean oil.",10.1002/(sici)1099-0690(200004)2000:8<1521::aid-ejoc1521>3.0.co;2-f,2000-04-01,0.5803349235629043
Organic Letters,"A Novel, Facile Approach to Frondosin B and 5-<i>epi</i>-Liphagal <i>via</i> a New [4 + 3]-Cycloaddition","A new [4 + 3]-cycloaddition between benzofuran allylic alcohols and dienes, promoted by camphorsulfonic acid, has been identified. A novel strategy which used this cycloaddition as a key step has been developed for the synthesis of 6,7,5-tricyclic skeleta, and syntheses toward frondosin B (1) and 5-epi-liphagal (2) have been achieved via short routes in good yields.",10.1021/ol3020013,2012-08-13,0.5803333902107382
Journal of Organic Chemistry,"Bridged to Fused Ring Interchange. Methodology for the Construction of Fused Cycloheptanes and Cyclooctanes. Total Syntheses of Ledol, Ledene, and Compressanolide","The type two intramolecular Diels-Alder reaction (T2IMDA) is an efficient method for the formation of medium rings. The methodology is particularly effective for the construction of seven- and eight-membered rings. A strategy for the synthesis of functionalized cycloheptanes and cyclooctanes has been developed that involves a bridged to fused ring interchange. The T2IMDA provides a synthesis for rigid bridged bicyclic molecules that can be stereoselectively elaborated before ozonolysis of the bridgehead double bond. Following oxidative cleavage, aldol condensation provides fused bicyclic ring systems that otherwise are difficult to synthesize. This methodology is amenable to the synthesis of terpene natural products. This is demonstrated here through total syntheses of (+/-)-ledol and (+/-)-ledene and a formal synthesis of (+/-)-compressanolide.",10.1021/jo961005a,1996-01-01,0.5803225993697501
Journal of Organic Chemistry,Synthesis of Functionalized 3-Cyanoisoxazoles Using a Dianionic Reagent,"A series of 5-acylated 3-cyanoisoxazoles were efficiently synthesized by the Michael addition of dianionic cyano-aci-nitroacetate to α-chloro-α,β-unsaturated ketones followed by intramolecular nucleophilic substitution of the nitronate ion intermediate. In this process, the dianionic reagent serves as the safe synthetic equivalent of the explosive nitroacetonitrile. The 3-cyano group is sufficiently reactive toward ethanolysis and 1,3-dipolar cycloaddition with an azide to afford ethyl ester and tetrazole, respectively. A pyridine ring between the 5-acyl and the 4-aryl group was also constructed. This led to the formation of the isoxazolo[5,4-c]quinoline derivative.",10.1021/acs.joc.7b00811,2017-05-04,0.5803206805589697
Organic Letters,Regioselective Synthesis of Substituted Cyclopenta[<i>l</i>]phenanthrenes,"A simple and efficient synthesis of cyclopenta[l]phenanthrenes from substituted acetophenones provides access to polycyclic aromatics with a variety of substitution patterns. The synthesis requires only three steps from a silyl enol ether: a Mukaiyama aldol reaction followed by McMurry coupling and then Mallory photocyclooxidation to give the target phenanthrenes. Photocyclization conditions have been found that give regioselective formation of 2,7-phenanthrenes from bis(meta-substituted) stilbenes.",10.1021/acs.orglett.6b02008,2016-08-22,0.5803115511224327
Journal of Organic Chemistry,"Chiral Amino Alcohols As Intermediates in the Stereocontrolled Synthesis of 1,3-Disubstituted Tetrahydroisoquinolines and Protoberberines","An efficient stereocontrolled synthetic approach to (3 S )-3-aryltetrahydroisoquinoline 3d and (1 S,3 S )-3-aryl-1-methyltetrahydroisoquinolines 3a − c by a Pictet−Spengler heterocyclization reaction of optically active (95% ee) ( S )-1,2-diarylethylamines 2a − c is presented. An alternative route toward obtaining the epimeric derivative of 3a, tetrahydroisoquinoline (1 R,3 S )- 6, was also achieved by a stereocontrolled ring opening process carried out on the oxazolotetrahydroisoquinoline 9 . Tetrahydroisoquinoline 8 was employed for the stereoselective preparation of (5 S,6 S,14 S )-6-phenyl-2,3,10,11-tetramethoxyprotoberberin-5-ol (12), a new type of 5,6-disubstituted protoberberine derivative with excellent (d.e>95% by 1 H NMR) stereoselection.",10.1021/jo981326h,1999-01-27,0.5803112859383792
Synlett,A New Two Steps Synthesis of α-Substituted γ-Methyl γ-Lactones from Nitroalkanes,"All articles of this category α-Substituted γ-methyl γ-lactones are efficiently prepared, in two steps, by regiospecific Michael addition of nitroalkanes to methyl trans -4-oxo-2-pentenoate in MeCN/DBU followed by chemoselective reduction of the obtained enones with NiCl 2 ⋅6H 2 O/NaBH 4 . By this method a variety of functionalized 3,5-disubstituted butyrolactones can be obtained. Nitroalkanes - trans -4-oxo-2-pentenoate - α-substituted γ-methyl γ-lactones - Michael addition - nickel boride",10.1055/s-1996-5667,2000-12-31,0.5803036641830298
Journal of Organic Chemistry,"Synthesis of 2-substituted 5,7,8-trimethyl-6-hydroxythiochromans and purported syntheses of sulfur-containing analogs of vitamin E","The syntheses of 5,7,8-trimethyl-, 2,5,7,8-tetramethyl-, and 2,2,5,7,8-pentamethyl-6-hydroxythiochromans have been achieved by a Michael-type condensation of methyl acrylate and related methyl esters with 2,3,5-trimethyl-4-hydroxythiochromans followed by cyclization of the free acid and reduction. These three previously unknown compounds can serve as simple models for the still unknown 1-thia-α-tocopherol (1), which could not be prepared by this route. Indeed, two purported syntheses of 18,9 have been shown to yield an essentially identical mixture of five isomers of the desired compound. For three components in this mixture, including the two major products, it is highly probable that the initial condensation at sulfur has not been followed by ring closure.",10.1021/jo00360a013,1986-05-01,0.5803011801920048
Tetrahedron,Diastereoselective synthesis of α-amino-β-hydroxyacids,,10.1016/s0040-4039(01)91236-5,1984-01-01,0.5803004321232378
Tetrahedron,A new route to 2-substituted Δ2-thiazolines: Stille cross-couplings of 2-bromo-Δ2-thiazolines,,10.1016/0040-4039(96)00970-7,1996-07-01,0.5802964925411159
Organic Letters,Amine-Mediated Transimination and Aromatization-Triggered Domino Reaction in the Synthesis of Polyfunctionalized 4-Aminoquinolines,"Dearomatization provides numerous possibilities for the development of new transformative modes of aromatic compounds. A conceptually novel metal-free multicomponent domino reaction of the dearomatized products of 2-alkynylanilines is developed. The reaction involves the secondary amine-mediated transimination with α-amino nitriles and subsequent aromatization-triggered cascade rearrangement, nucleophilic cyclization, and retro-Strecker reaction. This process provided a new practical method for the rapid synthesis of polyfunctionalized 4-aminoquinolines from readily available starting materials.",10.1021/acs.orglett.6b02643,2016-10-05,0.5802963611011988
Journal of Organic Chemistry,Double Intramolecular S<sub>N</sub>‘ <i>O</i>-Cyclization for Stereoselective Synthesis of Bistetrahydrofuran Core of Acetogenins,"A C 2 -symmetric bistetrahydrofuran core of acetogenins has been prepared via double intramolecular S N ‘ O -cyclization reactions. Approaches using readily prepared both E - and Z -olefin substrates are investigated. The cyclization of E -olefins gave a mixture of two diastereomers with low selectivity, while the corresponding Z -olefins predominantly provided a desired trans, trans -bistetrahydrofuran product. The high diastereoselectivity is presumably controlled by a hydrogen-bonding transition state. An efficient enantioselective synthesis of this C 2 -symmetric bistetrahydrofuran is also described. Sharpless asymmetric dihydroxylation was used for this approach.",10.1021/jo981771c,1999-03-17,0.5802947293080108
Organic Letters,Total Synthesis of Cristatic Acid,"The first total synthesis of cristatic acid 1, an antibiotic endowed with considerable activity against Gram-positive bacteria, hemolytic properties, and significant cytotoxicity, is described. Key to success are the formation of its 2,4-disubstituted furan moiety via a palladium-catalyzed alkylation of vinylepoxide 10 derived from sulfonium salt 8 and the use of SEM ethers as the protecting groups for the phenolic OH functions.",10.1021/ol0061236,2000-07-13,0.5802936049341078
Organic Letters,Total Synthesis of (±)-Goniomitine via a Formal Nitrile/Donor−Acceptor Cyclopropane [3 + 2] Cyclization,The total synthesis of (+/-)-goniomitine has been accomplished in 17 linear steps with 5.2% overall yield starting from commercially available delta-valerolactam. A synthetic highlight includes the first application of a formal [3 + 2] cycloaddition between a highly functionalized nitrile and a donor-acceptor cyclopropane to prepare an indole nucleus. The use of a microwave reactor is shown to greatly improve the reaction times for two steps.,10.1021/ol702376j,2007-12-18,0.580291766964211
Journal of the American Chemical Society,Synthesis and Structure Revision of Nakiterpiosin,"This manuscript describes a convergent synthesis and the revision of the relative stereochemistry of nakiterpiosin, a marine C-nor-D-homosteroid. Our synthesis features a late-stage carbonylative Stille cross-coupling reaction and a photo-Nazarov cyclization reaction that deliver the complete nakiterpiosin skeleton efficiently.",10.1021/ja808110d,2008-11-08,0.5802856940505454
Organic Letters,Direct <i>C</i>-Glycosylation of Organotrifluoroborates with Glycosyl Fluorides and Its Application to the Total Synthesis of (+)-Varitriol,"A mild, stereoselective, and quick approach to accessing alkynyl and alkenyl C-glycosides via BF(3)·Et(2)O promoted coupling of organotrifluoroborates and glycosyl fluorides is reported. The application of this method was further demonstrated by the concise and efficient total synthesis of (+)-varitriol in only seven steps.",10.1021/ol102473k,2010-11-29,0.5802847392121459
Angewandte Chemie International Edition,Enantioselective Divergent Total Syntheses of Cycloaurenones and Dysiherbols,"Cycloaurenones and dysiherbols are naturally occurring sesquiterpene quinones/quinols that share a 6/6/5/6 tetracyclic carbon skeleton with either a cis- or trans-decalin system containing four contiguous stereocenters, including three contiguous all-carbon quaternary stereocenters. Total syntheses of cycloaurenones have not been reported. Herein, we present the first enantiodivergent syntheses of cycloaurenones and dysiherbols based on manipulation of a common cyclohexadienone intermediate: namely, a local desymmetric Giese-Baran-type cyclization for cycloaurenones and a copper-catalyzed enantioselective conjugate addition for dysiherbols. Moreover, the key cyclohexadienone intermediate was readily accessible by a bidirectional approach from a chiral bis-Weinreb amide. The 1,4-nonadjacent stereocenters were installed by an unprecedented enantioselective hydrogenation of the corresponding bis-α,β-unsaturated Weinreb amide (>99:1 chiral/meso ratio, >99% enantiomeric excess).",10.1002/anie.202507638,2025-04-15,0.5802819919917159
Organic Letters,Synthesis of Enantioenriched <i>gem</i>-Disubstituted 4-Imidazolidinones by Palladium-Catalyzed Decarboxylative Asymmetric Allylic Alkylation,"A variety of enantioenriched gem -disubstituted 4-imidazolidinones were prepared in up to >99% yield and 95% ee by the Pd-catalyzed decarboxylative asymmetric allylic alkylation of imidazolidinone-derived β-amidoesters. In the process of preparing these substrates, a rapid synthetic route to 4-imidazolidinone derivatives was developed, beginning from 2-thiohydantoin. The orthogonality of the benzoyl imide and tert -butyl carbamate groups used to protect these nitrogen-rich products was demonstrated, enabling potential applications in drug design.",10.1021/acs.orglett.1c02134,2021-08-04,0.5802802468158025
Organic Letters,A Rhodium(I)-Catalyzed Demethylation−Cyclization of <i>o-</i>Anisole-Substituted Ynamides in the Synthesis of Chiral 2-Amido Benzofurans,A Rh(I)-catalyzed demethylation-cyclization sequence for a direct transformation of o-anisole-substituted ynamides to benzofurans is described here. The Ag salt functions synergistically with Rh(I) for the key demethylation step.,10.1021/ol0707362,2007-05-10,0.580277069413619
Tetrahedron,Synthesis of a novel tetrafluoropyridine-containing amino acid and tripeptide,,10.1016/j.tetlet.2013.06.124,2013-07-08,0.5802757750041052
European Journal of Organic Chemistry,"A Cobalt‐Catalyzed Multicomponent Approach to Novel 2,3‐Di‐ and 2,2,3‐Trisubstituted 3‐Methoxycarbonyl‐γ‐butyrolactones","Abstract A one‐pot, three‐component synthesis of the title butyrolactones starting from aryl bromides, dimethyl itaconate, and either aldehydes or ketones is described. The cobalt‐catalyzed domino process formally involves the in situ metalation of an aromatic bromide, conjugate addition onto dimethylitaconate, an aldolization reaction with a carbonyl compound and a final cyclization into a five‐membered lactone. This procedure is applied to the concise synthesis of a range of functionalized γ‐butyrolactones with a methyl paraconate subunit.",10.1002/ejoc.201000698,2010-08-03,0.5802753122139289
Organic Letters,Efficient Chirality Transfer in the SmI <sub>2</sub> -Mediated Cyclization of Aldehydo β-Alkoxyvinyl Sulfoxides:  Asymmetric Synthesis of 3-Hydroxyoxanes,Stereoselective syntheses of 3-hydroxyoxanes were achieved via efficient chirality transfer in the SmI2-mediated cyclization reactions of aldehydo beta-alkoxyvinyl sulfoxides.,10.1021/ol071176+,2007-07-21,0.5802726850174798
Synlett,The First Catalytic Enantioselective Synthesis of (R)-(+) Lasiodiplodin,"All articles of this category The first catalytic enantioselective route to (R)-(+) Lasiodiplodin is described. Introduction of the asymmetric center was accomplished by the enantioselective addition of dimethyl zinc to an aldehyde, mediated by a tricarbonyl (η6 arene) chromium(0) catalyst.",10.1055/s-1993-22460,1993-01-01,0.5802726438719554
Journal of Organic Chemistry,"Development of Multidentate P,P,N,N-Ligands for Ruthenium-Catalyzed Enantioselective Hydrogenation of 2-Pyridyl Ketones","A series of ferrocene-based chiral multidentate P,P,N,N-ligands were successfully designed and synthesized. They can be directly prepared via a one-step nucleophilic substitution reaction from ( S )-1-[( R )-2-(diphenylphosphino)ferrocenyl] ethyl acetate [( S C, R FC )-BPPFOAc]. Their ruthenium complexes were used in the asymmetric hydrogenation of 2-pyridyl ketones under mild conditions, the target chiral 1-aryl- or 1-alkyl-(pyridine-2-yl)methanols were obtained with high yields and excellent enantioselectivities. The synthetic utility of this reaction was demonstrated through its utilization in the preparation of key intermediates for a RAS inhibitor and the antihistamine drug Carbinoxamine.",10.1021/acs.joc.5c00548,2025-05-29,0.5802719037618287
Tetrahedron,"Naturally occurring benzofuran: isolation, structure elucidation and total synthesis of 5-(3-hydroxypropyl)-7-methoxy-2-(3′-methoxy-4′-hydroxyphenyl)-3-benzo[b]furancarbaldehyde, a novel adenosine A1 receptor ligand isolated from salvia miltiorrhiza bunge (danshen)",,10.1016/s0040-4039(00)78908-8,1991-04-01,0.5802704715169482
Journal of Organic Chemistry,<i>N</i>-Arylazetidines: Preparation through Anionic Ring Closure,"We report herein an efficient synthesis of diversely substituted N-aryl-2-cyanoazetidines based on an anionic ring-closure reaction. These compounds can be prepared from β-amino alcohols in enantiomerically pure form through a three-step sequence involving (i) copper-catalyzed N-arylation, (ii) N-cyanomethylation of the secondary aniline, and (iii) one-pot mesylation followed by ring closure induced by a base. This high-yielding sequence gives access to azetidines with a predictable and adjustable substitution pattern and also with predictable diastereoselectivity. These compounds are susceptible to multiple further derivatizations through Suzuki coupling or nitrile transformation, thus appearing as valuable new scaffolds for medicinal chemistry. Their rigid shape, featuring an almost planar N-arylamine and a planar four-membered ring, was revealed by both AM1 calculations and X-ray crystallography.",10.1021/acs.joc.6b00169,2016-03-01,0.5802628565264868
European Journal of Organic Chemistry,Synthesis of Diarylamines and Methylcarbazoles and Formal Total Synthesis of Alkaloids Ellipticine and Olivacine,"Abstract New and efficient strategies for the conversion of 4‐oxazolin‐2‐ones into 1‐methyl and 1,4‐dimethyl 3‐formylcarbazoles are herein described. Highly convergent cascade and one‐pot processes afforded the corresponding diarylamines, as in situ formed synthetic intermediates or final products in high overall yields. Special attention was given to the synthesis of methylated carbazoles by reacting 4,5‐dimethyl‐4‐oxazolin‐2‐ones with enones under microwave irradiation. The carbazole scaffold was provided by the palladium(II)‐catalyzed double C−H activation to generate oxidative cyclization of diarylamines. This methodology allowed for formal total syntheses of four naturally occurring pyrido[4,3‐ b ]carbazole alkaloids ellipticine, 9‐methoxyellipticine, olivacine, and 9‐methoxyolivacine.",10.1002/ejoc.202200364,2022-05-25,0.5802542491510109
Synthesis,A Versatile Approach to Anti-Asthmatic Compound CMI-977 and its Six-Membered Analogue,(opens in new window) Buy Article (opens in new window) Permissions and Reprints (opens in new window) All articles of this category (opens in new window) The synthesis of the anti-asthmatic compound CMI-977 is described. The tetrahydrofuran ring was effectively constructed by involving olefin metathesis while the stereoselective introduction of the 1- N -hydroxyureidylbut-3-yn-4-yl side-chain was achieved by C-alkylation of the 2-benzenesulfonyl derivative. anti-asthmatic - olefin metathesis - stereoselective synthesis - tetrahydrofuran - tetrahydropyran - nucleophilic displacement,10.1055/s-2000-6376,2000-01-01,0.5802525521745094
Journal of Organic Chemistry,Synthesis of 2-Substituted Polyhydroxytetrahydropyrimidines (<i>N</i>-Hydroxy Cyclic Guanidino-Sugars):  Transition-State Mimics of Enzymatic Glycosidic Cleavage,"The synthesis of 2'-substituted polyhydroxytetrahydropyrimidines as transition-state mimics of enzymatic glycosidic cleavage has been achieved by using guanylation and cyclization methodologies. The D-galacto type N-hydroxy cyclic guanidino-sugar 21 was synthesized in six steps from amine 7 and thiourea 14 in an overall yield of 59%. To further derivatize compound 21 to incorporate the leaving group moiety, we have synthesized 2-methylsulfanyl compounds 26-29 as key intermediates. The 2-methylsulfanyl group in 29 was displaced with amines, assisted by silver tetrafluoroborate as Lewis acid, to give protected cyclic guanidines 30-32 in moderate yields (60-67%). Removal of the protecting groups in 32 gave the D-galacto-type N-hydroxy cyclic guanidino-sugar 34. The key steps in the synthesis of the 6-deoxy-DL-galacto type N-hydroxy cyclic guanidino-sugars 49, 54, and 64-66 involve cyclization of the appropriate acetal intermediates (45, 50, and 58-60) followed by removal of the protecting groups.",10.1021/jo9915574,2000-03-28,0.5802524722035597
Organic Letters,Catalytic Enantioselective Synthesis of (−)-Podophyllotoxin,The first catalytic enantioselective total synthesis of (-)-podophyllotoxin is accomplished by a challenging organocatalytic cross-aldol Heck cyclization and distal stereocontrolled transfer hydrogenation in five steps from three aldehydes. Reversal of selectivity in hydrogenation led to the syntheses of other stereoisomers from the common precursor.,10.1021/acs.orglett.7b03236,2017-12-06,0.5802483588927878
Tetrahedron,"An efficient stereoselective synthesis of (2S,3S)-3-hydroxy-2-phenylpiperidine",,10.1016/j.tetlet.2003.11.103,2003-12-10,0.5802480997280894
Synthesis,Total Synthesis of Isatisindigoticanine H,Abstract The first total synthesis of the naturally occurring isatisindigoticanine H has been completed by employing D-mannitol as the chiral pool precursor to install the requisite stereochemistry of the natural product. Construction of the thiazole unit by dehydrative cyclization of a α-halo ketone with thiourea followed by Sandmeyer’s reaction and subsequent nucleophilic addition of lithiated bromothiazole to the Weinreb amide are the key reactions employed in this regard.,10.1055/a-2618-0514,2025-05-21,0.5802448425049117
Organic Letters,"Highly Stereoselective Synthesis of 1,2-Disubstituted Indanes by Pd-Catalyzed Heck/Suzuki Sequence of Diarylmethyl Carbonates","A palladium-catalyzed Mizoroki–Heck-type cyclization/Suzuki–Miyaura cross-coupling cascade of diarylmethyl carbonates with arylboronic acid derivatives has been developed to deliver the corresponding 1,2-disubstituted indanes in good yields with high diastereoselectivity ( trans / cis > 20:1). The key to achieve the high chemoselectivity and stereoselectivity is the use of the tris[3,5-di( tert -butyl)-4-methoxyphenyl]phosphine (DTBMP) ligand of remote steric hindrance. Moreover, the asymmetric synthesis is possible by the enantiospecific, stereoinvertive reaction of the optically active starting substrates to form the chiral indanes with high stereochemical fidelity (>98% es).",10.1021/acs.orglett.0c00945,2020-04-03,0.5802418259686806
Synlett,Systematic Synthesis of Diastereomeric THF Ring Cores and Total Synthesis of Anti-Tumor Annonaceous Acetogenins,"We have developed a systematic synthesis of the poly-THF ring cores of anti-tumor Annonaceous acetogenins by utilizing asymmetric alkynylation and subsequent stereodivergent THF ring formation as key steps. The asymmetric alkynylation of α-oxyaldehyde and α-tetrahydrofuranic aldehyde with an (S)-3-butyne-1,2-diol derivative proceeded in good yield with very high diastereo­selectivity. These adducts were converted into mono- and bis-THF cores by two different methods involving one-pot THF ring formation. The total syntheses of murisolin, 16,19-cis-murisolin, and longimicin D, which show cytotoxic activity against the human ­tumor cell, were accomplished by applying this methodology.",10.1055/s-2006-939688,2006-04-24,0.5802393871252072
Angewandte Chemie International Edition,"Brønsted Base Catalyzed One‐Pot Synthesis of Stereodefined Six‐Member Carbocycles Featuring Transient Trienolates and a Key Intramolecular 1,6‐Addition","A catalyst-driven one-pot reaction sequence is developed for the enantio- and diastereoselective synthesis of tetrasubstituted cyclohexenes from simple unsaturated ketones or thioesters. The method involves a tertiary amine/squaramide-catalyzed α-selective addition of transiently generated trienolates to nitroolefins, subsequent base-catalyzed double bond isomerization, and an intramolecular (vinylogous) 1,6-addition reaction, a rare key carbocyclization step that proceeded with essentially perfect stereocontrol.",10.1002/anie.201908693,2019-08-01,0.5802390355472721
European Journal of Organic Chemistry,Stereoselective Total Synthesis of Polyrhacitides A and B,"Abstract Two aliphatic polyketide natural products, polyrhacitides A and B, have been synthesized in a concise and highly stereoselective manner. The synthesis involved an auxiliary‐based acetate aldol reaction to generate the initial stereogenic center and an iterative Wittig reaction, intramolecular oxa‐Michael addition, and chelation‐controlled reduction reaction as the key steps to generate additional stereocenters. One‐pot acid‐mediated global deprotection and cyclization reactions shape the final bicyclic lactone core.",10.1002/ejoc.201100888,2011-09-23,0.5802379819820402
Journal of Organic Chemistry,A Concise Synthesis of (+)-Cerulenin from a Chiral Oxiranyllithium,"(+)-Cerulenin, a potent fungal inactivator of fatty acid synthases, has been prepared in optically pure form by a sequence involving reaction of a chiral oxiranyllithium with (4E,7E)-nonadienal. Synthesis of the former takes advantage of a particularly favorable Sharpless epoxidation and metalation to a configurationally stable organolithium, while the latter is available in quantity by a direct and improved route.",10.1021/jo9618177,1997-02-01,0.5802354272903397
Synthesis,"Total Synthesis of Koninginin D, B and E","All articles of this category Total synthesis of koninginin D, E and B was described. The structures of koninginin B and F, which were deduced as C 4 epimer of koninginin E and D, respectively, have been corrected. total synthesis - antibiotics - koninginins - (+)-tartaric acid - heterocycles",10.1055/s-2001-9741,2001-01-01,0.5802352228016541
Organic Letters,"Synthesis of Tetrasubstituted 1,4-Dicarbonyl (<i>Z</i>)-2,3-Dihaloalkenes via Electrophilic Halogenation of Alkynyl Hydrazones","A highly practical and stereoselective route to 1,4-dicarbonyl 2,3-dihaloalkenes is presented. The strategy involves bench-stable unprotected alkynyl hydrazones and commercially available N -halosuccinimides that provide γ-oxo-α,β-( Z )-dihaloenoates in excellent yields with complete Z -selectivity. The protocol also furnishes vicinal dihaloalkenes with two different halogen atoms. Also, a straightforward one-pot synthesis of dihaloenoates from readily accessible 2-oxo-3-butynoate is demonstrated. In addition, potential synthetic transformations of 4-oxo-2,3-dibromoenoates are explored, which include the synthesis of valuable five- and six-membered heterocycles.",10.1021/acs.orglett.3c02864,2023-09-25,0.5802329757750047
Tetrahedron,Regioselective schiff's base mediated deglycosidation of digitalis glycosides. New efficient synthesis of digoxigenin bis-digitoxoside and digoxigenin mono-digitoxoside,,10.1016/0040-4039(94)02212-t,1995-01-01,0.5802313627663185
Synthesis,A Synthesis of 4-Chloro-2-(trichloromethyl)pyrimidines and Their Study in Nucleophilic Substitution,"A convenient two-step, one-pot synthesis of 4-chloro-2-(trichloromethyl)pyrimidines starting from 2-(trichloromethyl)-1,3-diazabutadienes is described. These nitrogen heterocycles were prepared by a sequential acylation/intramolecular cyclization reaction between 2-(trichloromethyl)-1,3-diazabutadienes and acyl chlorides in the presence of triethylamine followed by treatment with POCl3. This is the first report for the synthesis of this type of 4-chloro-2-(trichloromethyl)pyrimidine derivatives and serves as a source for a wide variety of other substituted pyrimidines by nucleophilic substitution reactions.",10.1055/s-0037-1610270,2018-09-11,0.5802307674104317
Synlett,"Asymmetric Organozincate Additions to Ethyl 2,2,2-Trifluoropyruvate","A chromatography-free synthesis of enantiomerically enriched chiral α-trifluoromethyl α-hydroxy acids prepared via an asymmetric (R)-BINOL-mediated organozincate addition to ethyl 2,2,2-trifluoropyruvate (1) is reported.",10.1055/s-2007-984911,2007-07-20,0.5802262687016387
European Journal of Organic Chemistry,A Route to Benzo‐Annelated δ‐Sultams through Michael Cyclization,"Abstract A new approach to benzo‐annelated δ‐sultams containing an aryl–nitrogen bond is described. The method, which involves the intramolecular Michael cyclization of tert ‐butyl ortho ‐[ N ‐(methoxycarbonylmethyl)sulfonylamino]cinnamates, allows the synthesis of secondary sultams as well as their tertiary analogues and bridged tricyclic derivatives efficiently and diastereoselectively.",10.1002/ejoc.201403416,2015-01-15,0.5802260616317296
Tetrahedron,"Alkylation of α,α-dichloroarylmethane with trialkylboranes: Synthesis of alkylarylcarbinols",,10.1016/0040-4039(95)01870-n,1995-11-01,0.5802244213119482
Tetrahedron,Synthesis of α- and β-D-mannofuranosides via 1-O-alkylation,,10.1016/0040-4039(80)80235-8,1980-01-01,0.5802244213119482
Tetrahedron,Synthesis of α- and β-glycopyranosides via 1-0-alkylation,,10.1016/0040-4039(80)80236-x,1980-01-01,0.5802244213119482
Tetrahedron,"Synthesis, deprotonation, and alkylation of S-allyl sulfoximines",,10.1016/0040-4039(91)80202-h,1991-11-01,0.5802244213119482
Journal of Organic Chemistry,Bioinspired Asymmetric Synthesis of (−)-Gymnothelignan V,"A bioinspired asymmetric total synthesis of a structurally unique subtype of lignan, namely, (-)-gymnothelignan V, was achieved. The key synthetic sequences involved reduction of the eupomatilone skeleton leading to (-)-gymnothelignan J followed by the formation of the corresponding oxocarbenium ion and stereoselective intramolecular Friedel-Crafts reaction. Our synthetic approach provides the information to support the plausible biosynthetic pathway of this structurally unusual lignan. On a similar basis, other structurally related natural and non-natural gymnothelignans including (-)-gymnothelignan D, 6,9-bis- epi-gymnothelignan V, and 5- epi-gymnothelignans D and J were readily prepared.",10.1021/acs.joc.8b00164,2018-03-02,0.580221894406545
European Journal of Organic Chemistry,Phosphite‐Mediated Synthesis of Benzimidazoles: A One‐Pot Four‐Component Approach from Nitrophenols,Abstract Benzimidazoles may be formed in high yield through the phosphite‐triggered reductive cyclization of o ‐nitroaniline derivatives. This reaction was used for the one‐pot synthesis of benzimidazoles from o ‐nitrophenols and isocyanides. The mechanism is discussed in relation with nitroso intermediates.,10.1002/ejoc.201100939,2011-09-21,0.580214425115337
Journal of the American Chemical Society,Synthesis of Alkaloid (−)-205B via Stereoselective Reductive Cross-Coupling and Intramolecular [3+2] Cycloaddition,"An asymmetric synthesis of alkaloid (-)-205B, a tricyclic member of the architecturally diverse family of natural products isolated from the skin of neotropical poison frogs, is described that proceeds through two recently developed stereoselective synthetic methods: (1) Ti-mediated allylic alcohol-imine reductive cross-coupling and (2) intramolecular [3+2] cycloaddition of a glyoxylate-based homoallylic nitrone. The utility of this latter cycloaddition process for the assembly of the stereochemically dense piperidine core of 205B is noteworthy, as this method enables direct [3+2] cycloaddition of an intermediate homoallylic (E)-nitrone via a pathway that is stereochemically unscathed by competitive [3,3]-sigmatropic rearrangement processes. Overall, the synthesis is asymmetric, concise, and highly stereoselective-features which point to the potential future utility of these chemical methods in natural product synthesis and medicinal chemistry.",10.1021/ja306362m,2012-09-07,0.5802115941830779
Journal of Organic Chemistry,Meroterpenoid Synthesis via Sequential Polyketide Aromatization and Radical Anion Cascade Triene Cyclization: Biomimetic Total Syntheses of Austalide Natural Products,"The first total synthesis of five austalide natural products, (±)-17 S-dihydroaustalide K, (±)-austalide K, (±)-13-deacetoxyaustalide I, (±)-austalide P, and (±)-13-deoxyaustalide Q acid, was accomplished via a series of biomimetic transformations. Key steps involved polyketide aromatization of a trans, trans-farnesol-derived β,δ-diketodioxinone into the corresponding β-resorcylate, followed by titanium(III)-mediated reductive radical cyclization of an epoxide to furnish the drimene core. Subsequent phenylselenonium ion induced diastereoselective cyclization of the drimene completed the essential carbon framework of the austalides to access (±)-17 S-dihydroaustalide K, (±)-austalide K, and (±)-13-deacetoxyaustalide I via sequential oxidations. Furthermore, (±)-13-deacetoxyaustalide I could serve as a common intermediate to be derivatized into other related natural products, (±)-austalide P and (±)-13-deoxyaustalide Q acid, by functionalizing the cyclic lactone moiety.",10.1021/acs.joc.9b00142,2019-04-02,0.5802083641271875
Journal of Organic Chemistry,A Novel Synthetic Route to Sapphyrins,"New methodology has been developed for the synthesis of so-called sapphyrins, pentapyrrolic “expanded porphyrins”. An efficient approach involving acid-catalyzed condensation of 1,19-diunsubstituted a,c-biladienes and 3,4-dialkylpyrrole-2-carbaldehydes eliminates the preparation of bipyrrolic intermediates and allows the synthesis of sapphyrins with an unsymmetrical array of peripheral substituents. The β-substitution pattern of 2,3,13,17-tetraethyl-7,8,12,18,22,23-hexamethylsapphyrin has been unambiguously confirmed by single crystal X-ray crystallography. 1 H NMR spectra of the dication salts of sapphyrins are strongly dependent upon the counterions, and the pattern of resonances observed in solution is related to the stacking interactions between the macrocycles.",10.1021/jo9704117,1997-07-01,0.5802083077985665
Organic Letters,"Gold(I)-Catalyzed One-Pot and Diastereoselective Synthesis of <i>trans</i>-2-Silyl-4,5-dihydrofurans from Propargylsilanes and Aldehydes","A diastereoselective and high-yielding gold-catalyzed synthesis of trans -2-silyl-4,5-dihydrofurans is described. In addition to a sequential manner, this reaction could be performed in a one-pot procedure from propargylsilanes and aldehydes. A mechanistic proposal for the cis–trans isomerization step is formulated. To provide experimental support for this proposal, which involves ring opening/ring closing steps of the dihydrofuran, several isotopically labeled experiments, intramolecular capture of a proposed intermediate, and construction of a Hammett plot have been performed.",10.1021/acs.orglett.0c02356,2020-08-04,0.5802003161489945
Tetrahedron,"Novel photoreaction of 4-tribromomethyl-4-methyl-2,5-cyclohexadienone with amine",,10.1016/s0040-4039(00)78459-0,1994-11-01,0.5801934211832209
Journal of the American Chemical Society,Total Synthesis of Mucocin,"The synthesis of the potent antitumor agent, mucocin, 1, was efficiently achieved in 20 steps from cyclododecatriene, thus confirming the proposed structure of this unusual member of the Annonaceous acetogenins. Demonstrating the power of the “naked” carbon skeleton strategy, all seven asymmetric centers in the key fragment of the molecule were introduced by double AE reaction followed by double AD reaction. Simultaneous two ring closure reactions provided both the THP and THF rings in a single step.",10.1021/ja981302s,1998-10-27,0.5801925015241447
Organic Letters,Synthesis of Isoquinolines and Pyridines by the Palladium- and Copper-Catalyzed Coupling and Cyclization of Terminal Acetylenes,"3-Substituted isoquinolines have been synthesized by the coupling of aryl- and alkenyl-substituted terminal acetylenes with the tert -butylimine of o -iodobenzaldehyde in the presence of a palladium catalyst. Alkyl-substituted acetylenes fail to undergo this annulation process. However, the intermediate iminoalkynes containing aryl, alkenyl, and alkyl substituents produced from these palladium-catalyzed reactions undergo copper-catalyzed cyclization in excellent yields and short reaction times. Isoquinolines and pyridines have thus been prepared in a one-pot synthesis via coupling of aryl-, alkenyl-, and alkyl-substituted terminal acetylenes with the tert -butylimines of o -iodobenzaldehydes or 3-halo-2-alkenals in the presence of a palladium catalyst and subsequent copper-catalyzed cyclization of the resulting iminoalkynes. The total synthesis of the isoquinoline natural product decumbenine B has been accomplished in seven steps and 20% overall yield by employing this palladium-catalyzed coupling/cyclization methodology.",10.1021/ol990067v,1999-07-20,0.5801912542388312
Organic Letters,Total Synthesis of (−)-Phorbaketal A,A convergent asymmetric total synthesis of phorbaketal A was achieved in 10 steps through a Au(I)-catalyzed intramolecular spiroketalization reaction of an alkyne diol intermediate prepared from (R)-carvone and geranial. The spiroketalization reaction was regio- and stereoselective and was accompanied by isomerization of an exo-olefin into the trisubstituted olefin to form a unique spiroketal structure of phorbaketals.,10.1021/acs.orglett.7b01797,2017-07-06,0.580181098721292
Journal of Organic Chemistry,Synthesis of Tricolorin F,"A hetero-trisaccharide resin glycoside of jalapinolic acid known as tricolorin F has been synthesized. The approach involved the preparation of intermediate 5 and a subsequent coupling reaction with imidate 6 to produce disaccharide 7, which after deacetylation generated intermediate 8. A further coupling between this glycosyl acceptor and the quinovose glycosyl donor 9 resulted in the formation of the tricoloric acid C derivative 10. Basic hydrolysis afforded the intermediate 11, which was subsequently lactonized under Yamaguchi conditions to produce protected macrolactone 12. Removal of acetonide and benzyl protecting groups afforded pure tricolorin F (1).",10.1021/jo030244c,2004-01-06,0.5801777283258281
Angewandte Chemie International Edition,Catalytic Selective Cyclizations of Aminocyclopropanes: Formal Synthesis of Aspidospermidine and Total Synthesis of Goniomitine,"Mild control: Selective cyclization of aminocyclopropanes at either the N1 or C3 position of an indole ring was achieved by tuning the reaction conditions (see scheme). This strategy was applied to the formal synthesis of aspidospermidine and the total synthesis of goniomitine, which demonstrated significant cytotoxicity against several tumor cell lines (IC50=150–400 nM). Cbz=benzyloxycarbonyl, Ts=4-toluenesulfonyl.",10.1002/anie.201001853,2010-06-08,0.5801713216600137
Organic Letters,Concise Formal Synthesis of Porothramycins A and B via Zincke Pyridinium Ring-Opening/Ring-Closing Cascade,Short formal syntheses of the antitumor antibiotics porothramycins A and B from a commercially available ester of the unnatural amino acid 3-(3-pyridyl)alanine are presented. A rearrangement cascade that presumably involves a Zincke-type pyridinium ring-opening followed by cyclization of a pendant nucleophilic amide generates the salient pyrroline ring of the alkaloids.,10.1021/ol101035p,2010-06-08,0.580170670840759
Tetrahedron,Absolute stereochemistry of halichlorine; A potent inhibitor of VCAM-1 induction,,10.1016/s0040-4039(97)10714-6,1998-02-01,0.5801641143634576
Tetrahedron,"Studies toward the total synthesis of YW3699, a sesterterpenoid GPI biosynthesis inhibitor: preparation of the tri-substituted cyclooctene ring using the RCM reaction",,10.1016/j.tetlet.2009.02.163,2009-02-27,0.5801603189697866
Tetrahedron,A new synthesis of 3-ylidenephthalides via palladium-catalyzed cyclocarbonylation of 2-triflyloxyacetophenones,,10.1016/s0040-4039(00)79222-7,1993-06-01,0.5801594216066633
Synthesis,Novel Synthetic Approaches to (Trifluoromethyl)triazoles,"New synthetic procedures for the trifluoromethyl-substituted triazoles, 3-(trifluoromethyl)-4H-1,2,4-triazole and 4-(trifluoromethyl)-1H-1,2,3-triazole, have been elaborated. The target compounds were prepared from commercially available trifluoro­acethydrazide (one step) and methyl propiolate (three steps), respectively.",10.1055/s-0029-1218656,2010-01-29,0.5801555461705334
Angewandte Chemie International Edition,Enantioselective Iridium‐Catalyzed Allylic Substitution with 2‐Methylpyridines,"Abstract An enantioselective iridium‐catalyzed allylic substitution with a set of highly unstabilized nucleophiles generated in situ from 2‐methylpyridines is described. Enantioenriched 2‐substituted pyridines, which are frequently encountered in natural products and pharmaceuticals, could be easily constructed by this simple method in good yields and excellent enantioselectivity. The synthetic utility of the pyridine products is demonstrated through the synthesis of a key intermediate of a reported Na + /H + exchanger inhibitor and the total synthesis of (−)‐lycopladine A.",10.1002/anie.201700433,2017-03-07,0.5801546691583102
Journal of the American Chemical Society,Asymmetric Total Synthesis of (−)-VM55599:  Establishment of the Absolute Stereochemistry and Biogenetic Implications,The first asymmetric biomimetic total synthesis of VM55599 (13) has been achieved utilizing an intramolecular Diels-Alder cycloaddition as a key step. The synthetic material was utilized to elucidate the absolute stereochemistry of the natural product. The results are discussed in terms of a unified biogenesis of the paraherquamides and VM55599.,10.1021/ja017425l,2002-02-16,0.580154126629678
Organic Process Research & Development,"Development of a Novel Chemoenzymatic Process for (<i>S</i>)-1-(Pyridin-4-yl)-1,3-propanediol","We first developed a novel and efficient chemoenzymatic process to prepare ( S )-1-(pyridin-4-yl)-1,3-propanediol, a vital HepDirect prodrug intermediate, from inexpensive and commercially available isonicotinic acid. Through this process, we provide a creative way to obtain the key chiral intermediate, β-hydroxyester, with ketoreductase (KRED) EA. After optimization of the process, we performed the reaction on a 100 g scale with a substrate concentration of up to 150 g/L, a yield of 93%, and an ee value of up to 99.9%. Additionally, we used a simple and effective NaBH 4 /MgCl 2 reduction system to obtain ( S )-1-(pyridin-4-yl)-1,3-propanediol with >99.9% ee and an 80% yield. This novel chemoenzymatic process has the potential to be a cost-effective and environmentally friendly process suitable for industrial use.",10.1021/acs.oprd.0c00403,2020-11-25,0.5801539673217231
European Journal of Organic Chemistry,Synthesis of Aminocyclitols and Trihydroxylated Indolizidinone from a <scp>D</scp>‐Mannitol‐Derived Common Building Block,"Abstract The synthesis of 4‐amino‐4‐deoxy‐ muco ‐quercitol ( 22 ), 4‐amino‐4‐deoxy‐(–)‐ vibo ‐quercitol ( 27 ) and also a trihydroxylated indolizidinone 38 from D ‐mannitol is described using ring‐closing metathesis and diastereoselective dihydroxylation as the key steps.",10.1002/ejoc.201001171,2010-12-29,0.5801538645792194
Journal of Organic Chemistry,The Carbohydrate−Sesquiterpene Interface. Directed Synthetic Routes to Both (+)- and (−)-Fomannosin from <scp>d</scp>-Glucose,An enantiodivergent strategy for the total chemical synthesis of both naturally occurring (+)-fomannosin (1) and its (-)-antipode (ent-1) from alpha-D-glucose has been developed and successfully implemented. The key steps in the overall pathway include the following: (i) application of the zirconocene-mediated ring contraction of vinyl furanosides for the construction of highly substituted cyclobutanols; (ii) the use of ring-closing metathesis to form the pendant five-membered ring; (iii) making recourse to a monothio malonic ester to allow for chemoselective reduction to sensitive lactone intermediate 45; (iv) hydroxyl-directed dihydroxylation with OsO(4) to generate 48; and (v) sequential elimination via a cyclic sulfite and a cyclobutyl triflate. The bridge between the enantiomeric series consisted of a six-step linkup involving the structural modification of 22 so as to generate ent-30b. Optical activity was fully preserved throughout.,10.1021/jo8004233,2008-05-20,0.5801466895454823
Journal of the American Chemical Society,Total Synthesis of the Diazobenzofluorene Antibiotic (−)-Kinamycin C,"The enantioselective total synthesis of the diazobenzofluorene antibiotic (-)-kinamycin C is reported. The approach involves tartrate-mediated, asymmetric nucleophilic epoxidation of a functionalized quinone monoketal to construct the highly substituted D-ring.",10.1021/ja066621v,2006-10-26,0.580145909226923
Organic Letters,A Biomimetic Strategy to Access the Silybins: Total Synthesis of (−)-Isosilybin A,"We report the first asymmetric, total synthesis of (-)-isosilybin A. A late-stage catalytic biomimetic cyclization of a highly functionalized chalcone is employed to form the characteristic benzopyranone ring. A robust and flexible approach to this chalcone provides an entry to the preparation of the entire isomeric family of silybin natural products.",10.1021/ol503303w,2014-12-17,0.5801326438987691
Tetrahedron,"A norbornyl route to cyclohexitols: structural diversity in fragmentation through functional group switching. Synthesis of α- and β-galactose, α-talose and α-fucopyranose carbasugars",,10.1016/s0040-4039(00)00408-1,2000-04-01,0.5801314116632584
Tetrahedron,Synthesis and spectroscopic properties of 5-tert-butyl-3-(trifluoromethyl)phthalonitrile: a novel precursor for the synthesis of phthalocyanines,,10.1016/j.tetlet.2013.05.145,2013-06-09,0.580129585774068
Angewandte Chemie International Edition,Pot Economy in the Synthesis of Prostaglandin A<sub>1</sub> and E<sub>1</sub> Methyl Esters,"Pot luck: Prostaglandins regulate a broad range of physiological processes and some of their derivatives are used as effective drugs, but previously their preparation has required many steps. The title compounds were efficiently synthesized in a small number of synthetic steps by using a recently developed organocatalyst and practical, one-pot operations involving several successive reactions.",10.1002/anie.201209380,2013-02-13,0.5801263603308305
Journal of Organic Chemistry,Total Synthesis of a Few Naturally Occurring Isocoumarins and Dihydroisocoumarins: Successful Exploration of the Ag(I)-Mediated 6-<i>Endo</i>-<i>Dig</i> Cyclization and Asymmetric Hydrogenation Strategy,"We disclose the total synthesis of naturally occurring isocoumarins: ( S )-fusarimarin B, ( S )-diaporthin, (10 S )-8-methoxydiaporthin, ( S )-orthosporin, ( S )-monarubin B, ( S )-lunatinin, and isochromans aspergillumarin A, aspergillumarin B, and penicimarin B. The synthetic strategy highlights an efficient Ag(I)-mediated 6- endo - dig cyclization of properly substituted 2-alkynylated benzoates to yield the corresponding isocoumarins in excellent yields. The obtained isocoumarins, upon asymmetric hydrogenation with the Ru-BINAP catalyst, provided the corresponding isochromans with excellent yields and enantioselectivity. A Sonogashira cross-coupling reaction of properly functionalized terminal alkynes and substituted aryl bromides was employed to access 2-alkynylated benzoates. This report constitutes the first asymmetric synthesis of three naturally occurring isocoumarins: ( S )-fusarimarin B, and ( S )-monarubin B.",10.1021/acs.joc.5c00244,2025-03-21,0.5801249195047077
Tetrahedron,Stereoselective synthesis of the enantiomer of the key fragment of crocacin,,10.1016/j.tetlet.2004.05.130,2004-06-18,0.5801246198144009
Organic Letters,"Abbreviated Synthesis of the C3−C14 (Substituted 1,7-Dioxaspiro[5.5]undec-3-ene) System of Okadaic Acid","[formula: see text] Described is a novel, concise, and flexible synthesis of the C3-C14 portion of okadaic acid. A substituted valerolactone (C3-C8) was prepared in three steps and alpha-hydroxylated using Davis' oxaziridine. Conjugate addition of dimethylcuprate upon ynones derived from the C3-C8 lactones followed by intramolecular ketalization provided the C3-C14 fragment and revealed a significant role of the C7 alpha'-ketone substituent upon the efficiency of spiroketalization.",10.1021/ol9906615,1999-06-22,0.5801243585681017
Tetrahedron,"Efficient synthesis of (±)-8,14-cedranoxide using electrochemical method as a key step",,10.1016/s0040-4039(00)96939-9,1987-01-01,0.5801214742863998
Tetrahedron,On the total synthesis of (S)-methanophenazine and the formal synthesis of (R)-methanophenazine from a common precursor†Dedicated to Professor Dr. Horst Kunz on the occasion of his 60th birthday.†,,10.1016/s0040-4039(00)01669-5,2000-12-01,0.5801199794430657
Synthesis,A Novel Synthesis of the Enantiomers of an Antihistamine Drug by Piperazine Formation from a Primary Amine,"All articles of this category An enantioselective synthesis of each enantiomer of the antihistamine drug 2(2-{4-[(4-chlorophenyl)phenylmethyl]-1-piperazinyl}ethoxy)acetic acid dihydrochloride (1) is described, involving the preparation of the benzhydrylpiperazine portion of the molecule from reaction of each enantiomer of 4-chlorobenzhydrylamine with N,N -bis(2-chloroethyl)-4-methylbenzenesulfonamide. A modification of standard toluenesulfonamide deprotection with hydrogen bromide in acetic acid was introduced, substituting 4-hydroxybenzoic acid for phenol. enantiospecific synthesis of piperazine from primary amine - cetirizine",10.1055/s-1995-4013,1995-07-01,0.5801142407932702
Angewandte Chemie International Edition,"First, Atropo-Enantioselective Total Synthesis of the Axially Chiral Phenylanthraquinone Natural Products Knipholone and 6′-O-Methylknipholone","The first stereoselective access to an axially chiral arylanthraquinone, the antimalarial natural product knipholone (3), was achieved by application of the “lactone concept”. Key steps were the intramolecular coupling of the bromoester 1, to give the configurationally unstable biaryl lactone 2, and the enantioselective ring cleavage to form 3.",10.1002/1521-3773(20010504)40:9<1687::aid-anie16870>3.0.co;2-6,2001-05-04,0.5801055846216848
Angewandte Chemie International Edition,"First, Atropo-Enantioselective Total Synthesis of the Axially Chiral Phenylanthraquinone Natural Products Knipholone and 6′-O-Methylknipholone","The first stereoselective access to an axially chiral arylanthraquinone, the antimalarial natural product knipholone (3), was achieved by application of the “lactone concept”. Key steps were the intramolecular coupling of the bromoester 1, to give the configurationally unstable biaryl lactone 2, and the enantioselective ring cleavage to form 3.",10.1002/1521-3773(20010504)40:9<1687::aid-anie16870>3.3.co;2-y,2001-05-04,0.5801055846216848
European Journal of Organic Chemistry,"A Ramberg−Bäcklund Approach to the Synthesis ofC-Glycosides,C-Linked Disaccharides, andC-Glycosyl Amino Acids","Synthetic applications of exo-glycals, derived from S-glycoside dioxides using the Meyers variant of the Ramberg−Bäcklund rearrangement, are described. These include a formal synthesis of a β-glycosidase inhibitor 12 and an efficient route to spirocyclic glucose derivatives 17 and 18. The synthesis of C-linked disaccharides 24, 31, and 38 and the C-glycosyl amino acid 49 using the Ramberg−Bäcklund rearrangement is also reported. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)",10.1002/1099-0690(200204)2002:7<1323::aid-ejoc1323>3.0.co;2-8,2002-04-01,0.5800987365076841
Tetrahedron,An asymmetric synthesis of indole alkaloids,,10.1016/s0040-4039(00)98280-7,1985-01-01,0.580097210234905
Tetrahedron,"12-methylidene-10(Z), 13(Z)-nonadecadienoic acid, a new irreversible inhibitor of soybean lipoxygenase",,10.1016/s0040-4039(00)84856-x,1986-01-01,0.5800962035941546
Tetrahedron,Asymmetric synthesis of 3-hydroxyacids from aldehyde or dialkyl ketone,,10.1016/s0040-4039(01)84784-5,1972-01-01,0.5800907646240072
Synlett,Enantioselective Synthesis of (<i>R</i>)- and (<i>S</i>)-Cizolirtine; Application of Oxazaborolidine-Catalyzed Asymmetric Borane Reduction to Azolyl Phenyl Ketones,All articles of this category An efficient enantioselective synthesis of ( R )- and ( S )-cizolirtine 1 is described. The key step of the procedure is the CBS-oxazaborolidine asymmetric reduction of phenyl pyrazolyl ketone 2 . Related enantioselective reductions of several azolyl phenyl ketones are also reported. asymmetric synthesis - cizolirtine - oxazaborolidine - azolyl phenyl ketones - enantioselective reduction,10.1055/s-1999-2712,1999-06-01,0.5800888637048881
Synthesis,Efficient Synthesis of 2-Substituted 7-Azaindole Derivatives via Palladium-Catalyzed Coupling and C-N Cyclization Using 18-Crown-6,All articles of this category (opens in new window),10.1055/s-2007-983730,2007-06-18,0.5800882587714221
Angewandte Chemie International Edition,"Divergent Total Syntheses of Enmein‐Type Natural Products: (−)‐Enmein, (−)‐Isodocarpin, and (−)‐Sculponin R","Divergent total syntheses of the enmein-type natural products (-)-enmein, (-)-isodocarpin, and (-)-sculponin R have been achieved in a concise fashion. Key features of the strategy include 1) an efficient early-stage cage formation to control succeeding diastereoselectivity, 2) a one-pot acylation/akylation/lactonization to construct the C-ring and C8 quarternary center, 3) a reductive alkenylation approach to construct the enmain D/E rings and 4) a flexible route to allow divergent syntheses of three natural products.",10.1002/anie.201803709,2018-04-12,0.5800880680355325
Journal of Organic Chemistry,Convenient Route to Enantiopure Fmoc-Protected Morpholine-3-carboxylic Acid,"Enantiopure Fmoc-protected morpholine-3-carboxylic acid was synthesized from dimethoxyacetaldehyde and serine methyl ester through a short and practical synthetic route. The preparation consisted of a five-step process based on reductive amination, intramolecular acetalization, and concomitant elimination of the anomeric methoxy substituent, followed by hydrogenation of the double bond and final acidic ester hydrolysis. The optical purity of both enantiomers of the title amino acid was demonstrated by HPLC analysis of the corresponding amide derivatives obtained from coupling with chiral (S)-(-)-1-phenylethylamine. Moreover, the synthesis of a model tripeptide showed full compatibility of the title Fmoc-amino acid with solid-phase peptide synthesis, thus allowing the application of Fmoc-morpholine-3-carboxylic acid in peptidomimetic chemistry on the solid phase.",10.1021/jo070036a,2007-04-28,0.5800823888787369
Synlett,Stereoselective Synthesis of C1-C18 Region of Palmerolide A from Tartaric Acid,A stereoselective synthesis of the C1-C18 region of marine natural product palmerolide A from chiral pool tartaric acid is presented. The key synthetic sequence includes the elaboration of a gamma-oxo-amide derived from tartaric acid and alkene formation involving Boord type fragmentation.,10.1055/s-0029-1219797,2010-03-23,0.5800795748513028
European Journal of Organic Chemistry,Synthesis of a Fluorinated Ether Lipid Analogous to a Platelet Activating Factor,"The synthesis of racemic 2-fluoro-3-hexadecyloxy-2-methylprop-1-yl 2′-(trimethylammonio)ethyl phosphate (10), a fluorinated analogue of the anticancer active and blood platelet activating ether lipids 8 and 9, has been achieved in a six-step sequence from methallyl alcohol (11). Etherification of 11 with hexadecyl bromide gave allylic ether 12, bromofluorination of which afforded the bromo-substituted fluoride 13, which was subsequently transformed into the acetate 14. Hydrolysis of 14 gave the key intermediate 2-fluoro-2-(hexadecyloxymethyl)propanol (15), which was attached to the phosphocholine residue in the final step. Enzyme-catalyzed deracemization of the fluorohydrin 15 by acetylation with several lipases gave optically active compounds 14 and 15, with a maximum ee of 61% for 15 with Candida antarctica lipase catalysis after 74% conversion. An enantioselective synthesis of 10, based on a planned eight-step synthesis starting from α-methylstyrene, failed. The anticancer activity of racemic 10 has been observed in an in vivo model of methylcholanthrene-induced mouse fibrosarcoma.",10.1002/1099-0690(200112)2001:23<4501::aid-ejoc4501>3.0.co;2-j,2001-12-01,0.5800772969157565
Tetrahedron,The improved synthesis of β-D-glucuronides using TEMPO and t-butyl hypochlorite,,10.1016/s0040-4039(98)02565-9,1999-02-01,0.5800711529041668
Synlett,Stereoselective Total Synthesis of the Sesquiterpene (±)-Cameroonanol,We describe a stereoselective synthesis of the triquinane (±)-cameroonanol using the Lewis acid mediated [3+2] cyclo­addition of an allylsilane and a modified Fleming-Tamao oxidation as key steps.,10.1055/s-2007-982535,2007-06-01,0.580068086783972
Journal of Organic Chemistry,"The Total Synthesis of Tritiated and Deuterated 5-Oxo-ETE, a Novel Inflammatory Mediator","The total synthesis of 11,12,14,15-tetratritiated and deuterated 5-oxo-ETE is accomplished using a novel bisacetylene precursor 14 . The syntheses of these labeled derivatives are necessary in order to investigate further the role and biochemistry of the novel inflammatory mediator and eosinophilic chemotactic agent 5-oxo-ETE.",10.1021/jo980280p,1998-05-19,0.580065493997867
Tetrahedron,Modified synthesis of the peptidomimetic natriuretic peptide receptor-C antagonist M372049,,10.1016/j.tetlet.2020.151654,2020-01-22,0.5800585781480011
European Journal of Organic Chemistry,Synthesis of the Novel Amino Acid 4-Amino-3-(aminomethyl)benzoic Acid (AmAbz) and Its Protected Derivatives as Building Blocks for Pseudopeptide Synthesis,"4-Amino-3-(aminomethyl)benzoic acid (1) (AmAbz) is a novel unnatural amino acid with promise in applications as a building block for the synthesis of peptidomimetics and as a scaffold for combinatorial chemistry. It was efficiently synthesized in three steps (63% overall yield) from 4-aminobenzoic acid, by means of regioselective amidomethylation with hydroxymethylphthalimide. AmAbz (1) contains three distinct functionalities which could be discriminated from one another. Firstly, Boc2O or Fmoc−OSu reacted selectively with the benzylamino group to give the monoprotected derivatives AmAbz(Boc) (8a) or AmAbz(Fmoc) (8b), respectively. The absence of acylation at the arylamino group was also noticed in coupling experiments using the BOP reagent and building block 8b. This made protection of the arylamino group unnecessary either for peptide bond formation at the carboxyl group, or for subsequent elongation of a peptide chain at the benzylamino group. Finally, the arylamino group could be acylated under base-free, carbodiimide-mediated coupling conditions. These properties are illustrated by the solid-phase synthesis of the AmAbz-containing branched pseudopeptide Fmoc−Ala−Phe−AmAbz(H−Lys−Leu)−Val−Gly−NH2 (15). The synthesis of Fmoc−AmAbz(Boc) (10) is also described.",10.1002/1099-0690(200011)2000:22<3755::aid-ejoc3755>3.0.co;2-i,2000-11-01,0.5800565922756888
European Journal of Organic Chemistry,Synthesis of the Novel Amino Acid 4-Amino-3-(aminomethyl)benzoic Acid (AmAbz) and Its Protected Derivatives as Building Blocks for Pseudopeptide Synthesis,"4-Amino-3-(aminomethyl)benzoic acid (1) (AmAbz) is a novel unnatural amino acid with promise in applications as a building block for the synthesis of peptidomimetics and as a scaffold for combinatorial chemistry. It was efficiently synthesized in three steps (63% overall yield) from 4-aminobenzoic acid, by means of regioselective amidomethylation with hydroxymethylphthalimide. AmAbz (1) contains three distinct functionalities which could be discriminated from one another. Firstly, Boc2O or Fmoc−OSu reacted selectively with the benzylamino group to give the monoprotected derivatives AmAbz(Boc) (8a) or AmAbz(Fmoc) (8b), respectively. The absence of acylation at the arylamino group was also noticed in coupling experiments using the BOP reagent and building block 8b. This made protection of the arylamino group unnecessary either for peptide bond formation at the carboxyl group, or for subsequent elongation of a peptide chain at the benzylamino group. Finally, the arylamino group could be acylated under base-free, carbodiimide-mediated coupling conditions. These properties are illustrated by the solid-phase synthesis of the AmAbz-containing branched pseudopeptide Fmoc−Ala−Phe−AmAbz(H−Lys−Leu)−Val−Gly−NH2 (15). The synthesis of Fmoc−AmAbz(Boc) (10) is also described.",10.1002/1099-0690(200011)2000:22<3755::aid-ejoc3755>3.3.co;2-9,2000-11-01,0.5800565922756888
Synlett,Towards Glucosamine Building Blocks: Regioselective One-Pot Protection and Deallylation Procedures,Glucosamine building blocks have been prepared by an efficient regioselective one-pot protection approach. This synthetic route enabled the straightforward preparation of a glucosamine disaccharide in 73% yield. The system Pd(PPh3)4/TES was investigated as an alternative procedure for anomeric allyl ether deprotection.,10.1055/s-0030-1259001,2010-10-12,0.5800544774583142
Tetrahedron,"Efficient synthesis of 2,3-unsaturated sulfonamidoglycosides by Amberlyst 15",,10.1016/j.tetlet.2010.07.076,2010-07-20,0.5800449493868685
Tetrahedron,"Two-step, regioselective, multigram-scale synthesis of 2-(trifluoromethyl)indoles from 2-nitrotoluenes",,10.1016/j.tetlet.2021.153515,2021-10-29,0.5800440581828045
Synthesis,"A High-Yield Route to 1,2-Dihydrocyclobutabenzene-3,6-dicarboxylic Acid","All articles of this category A simple five-step method for preparing the previously unknown 1,2-dihydrocyclobutabenzene-3,6-dicarboxylic acid (XTA) in high yield is presented. All intermediates were crystalline compounds which allowed the preparation to be scaled up without complication. The title compound is of interest as a crosslinkable derivative of the widely used monomer, terephthalic acid (TA).",10.1055/s-1992-26354,1992-01-01,0.5800403973986115
Journal of Organic Chemistry,"Synthesis of Indolylquinolines, Indolylacridines, and Indolylcyclopenta[<i>b</i>]quinolines from the Baylis–Hillman Adducts: An in Situ [1,3]-Sigmatropic Rearrangement of an Indole Nucleus To Access Indolylacridines and Indolylcyclopenta[<i>b</i>]quinolines","A simple and easy route to the synthesis of a variety of structurally diverse indolylquinolines, indolylacridines, and indolylcyclopenta[b]quinoline derivatives via the reductive cyclization of C-alkylated indole derivatives, derived from acyclic as well as cyclic Baylis-Hillman adducts with indoles, is described. An unusual in situ [1,3]-sigmatropic rearrangement of the indole nucleus was observed during the reductive cyclicization of α-regioselective B-H adducts containing indoles to produce indolylacridines and indolylcyclopenta[b]quinoline derivatives.",10.1021/jo301313m,2012-09-12,0.5800327559372878
Journal of the American Chemical Society,Total Synthesis of (−)-Oridonin: An Interrupted Nazarov Approach,An enantioselective total synthesis of (−)-oridonin is accomplished based on a key interrupted Nazarov reaction. The stereochemistry of the Nazarov/Hosomi–Sakurai cascade was first explored to forge a tetracyclic skeleton with challenging quaternary carbons. A delicate sequence of two ring-rearrangements and late-stage redox manipulations was carried out to achieve the de novo synthesis of this highly oxidized ent -kauranoid.,10.1021/jacs.9b12034,2019-12-05,0.5800303920575418
Tetrahedron,Highly enantioselective synthesis of β-hydroxysulfonamides by asymmetric transfer hydrogenation,,10.1016/j.tetlet.2010.12.054,2010-12-22,0.5800280040601178
Journal of the American Chemical Society,Highly Diastereoselective Synthesis of Nucleoside Adducts from the Carcinogenic Benzo[<i>a</i>]pyrene Diol Epoxide and a Computational Analysis,"A diastereoselective synthesis of the nucleoside adducts corresponding to a cis ring-opening of the carcinogen (+/-)-7 beta, 8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BaP DE-2) by 2'-deoxyadenosine and 2'-deoxyguanosine is described. The key intermediate (+/-)-10alpha-amino-7beta,8alpha,9alpha-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene was synthesized by a highly diastereoselective dihydroxylation wherein phenylboronic acid was a water surrogate. The resulting boronate ester was converted to a tetraol derivative in which two of the four hydroxyl groups (trans 7, 8) were protected as benzoate esters while the remaining two (cis 9, 10) were free. The cis glycol entity was then subjected to a reaction with 1-chlorocarbonyl-1-methylethylacetate to yield an intermediate chloro monoacetoxy dibenzoate. Displacement of the halide with azide, complete cleavage of the esters, and catalytic reduction of the azide yielded the requisite amino triol. Fluoride displacement from appropriately protected nucleoside derivatives, 6-fluoropurine 2'-deoxyribonucleoside and 2-fluoro-2'-deoxyinosine, by the amino triol then yielded diastereomeric pairs of diol epoxide-adducted 2'-deoxyadenosine (dA) and 2'-deoxyguanosine (dG) nucleosides. Small aliquots of these adducts were separated for characterization purposes. The present approach provides the first diastereoselective synthesis of the cis adducts of BaP DE-2 with 2'-deoxyguanosine as well as the first synthesis of both dA and dG adducts from a common intermediate. An informative analysis of the 1H NMR spectra of the cis adducts synthesized and comparisons to the trans adducts are reported. To gain insight into the diastereoselectivity in the key dihydroxylation step, a computational analysis, including molecular mechanics (MMFF94) and semiempirical AM1 geometry optimizations, yielded results that are in fairly good agreement with the experimental observations.",10.1021/ja063902u,2006-12-13,0.5800279207514449
Organic Letters,Improved Synthesis for Modular Ascarosides Uncovers Biological Activity,"A versatile synthesis of modular ascarosides, a family of signaling molecules from Caenorhabditis elegans and other nematodes, via hydrogenolysis of a cyclic sulfate derived from methyl-α-l-rhamnopyranoside is reported. The route enables selective introduction of different side chains at the 1, 2, and 4 positions of the sugar, as demonstrated for ascarosides from C. elegans and Pristionchus pacificus. Bioassays with synthetic samples of 4'-tigloyl ascaroside mbas#3 revealed its role as an avoidance or dispersal signal.",10.1021/acs.orglett.7b01009,2017-05-17,0.5800258892953261
Tetrahedron,Asymmetric synthesis of (−)- and (+)-kainic acid using a planar chiral amide as a chiral building block,,10.1016/j.tetlet.2008.08.058,2008-08-23,0.5800228917777416
Organic Process Research & Development,"A Greener Approach for the Large-Scale Synthesis of 1,4,5-Trisubstituted Pyrazole, AZD8329","The development of a convenient, safe and scalable process for AZD8329 manufacturing is reported here. Synthesis was achieved in a two-step telescopic process with an excellent overall yield of 75%. In the first step enamine ( 6 ) was synthesized with 90% yield through three chemical transformations. In the next step AZD8329 was synthesized from the reactions of 6 and 4-hydrazinobenzoic acid hydrochloride 7 through two chemical transformations. The process is very efficient and economical, and AZD8329 was manufactured in multikilogram scale. A greener approach is demonstrated through usage of a minimum number of solvents and energy and with process mass intensity (PMI) <60 in the manufacturing process.",10.1021/op5001463,2014-07-02,0.5800223569811962
Tetrahedron,An efficient total synthesis of (±)-ar-tenuifolene,,10.1016/j.tetlet.2015.07.087,2015-08-04,0.5800211011473341
Organic Letters,Total Synthesis of Agelagalastatin,"The total synthesis of agelagalastatin, an antineoplastic glycosphingolipid, has been achieved. The synthesis involved an alpha-selective glycosylation of the ceramide moiety with the trisaccharide fluoride. The trisaccharide component was constructed employing the CB glycoside method which permitted a completely alpha-stereoselective galactofuranosylation.",10.1021/ol061444o,2006-08-01,0.5800210915260445
Organic Letters,Palladium-Catalyzed Intramolecular Trapping of the Blaise Reaction Intermediate for Tandem One-Pot Synthesis of Indole Derivatives,Palladium-catalyzed intramolecular N-arylative and N-alkylative/N-arylative trappings of the Blaise reaction intermediates could be a new route to construct the indole moiety in a tandem one-pot manner from nitriles.,10.1021/ol200045q,2011-02-18,0.5800178775440183
Organic Process Research & Development,"Synthesis of 2-Oxopropanethioamide for the Manufacture of Lanabecestat: A New Route for Control, Robustness, and Operational Improvements","A new route to 2-oxopropanethioamide, a key intermediate in the synthesis of lanabecestat (AZD3293/LY3314814), is described by employing commercially available 2,2-diethoxypropionitrile as a raw material. In contrast to the previous route, this work offers several advantages; for example, the raw material is safer to manufacture and handle, highly toxic hydrogen sulfide gas is no longer required as a reagent, and in situ FTIR spectroscopy monitoring has provided manufacturing controls and robustness. Additionally, this route offers a hold- and control-point by virtue of an isolable crystalline intermediate, which in turn provides improved quality that is evident in the downstream synthesis. An extensive design-of-experiment analysis was undertaken to understand multifactor interdependencies, build a model, visualize factor relationships, map the process parameter reaction space, identify potential process operating conditions, and predict their performance.",10.1021/acs.oprd.7b00170,2017-07-06,0.580017623747516
Organic Letters,A Stereocontrolled Annulation of the Taccalonolide Epoxy Lactone onto the Molecular Framework of <i>trans</i>-Androsterone,"A robust and scalable route to the taccalonolide skeleton starting from trans-androsterone is presented. The synthesis features a cyclic hydroboration carbonylation reaction, which effectively establishes the trans-hydrindane DE ring junction in a remarkable annulation reaction, as well as a Claisen rearrangement and a catalytic Ullmann-type cyclization. This work is part of a larger effort to uncover new clinical candidates from the taccalonolide class of anticancer agents through advances in chemical synthesis.",10.1021/acs.orglett.7b02349,2017-08-29,0.5800146469756988
European Journal of Organic Chemistry,"Efficient Synthesis of <i>tert</i>‐Butyl 2,4‐Dialkynylated and 2‐Alkynylated‐4‐Arylated‐1<i>H</i>‐Imidazole‐1‐Carboxylate <i>via</i> Regioselective Sonogashira Cross‐Coupling Reaction","Abstract An efficient regioselective cross‐coupling reactions of tert ‐butyl 2,4‐dibrominated‐5‐methyl‐1 H ‐imidazole‐1‐carboxylate is reported. This new synthetic route runs under simple and mild conditions and selectively gives an easy access to 2,4‐dialkynylated and 2‐alkynylated‐4‐arylated‐1 H ‐imidazole‐1‐carboxylate in good to excellent yields.",10.1002/ejoc.202100632,2021-07-30,0.5800139487158313
Organic Letters,<i>C</i><sub>1</sub>-Symmetric Dicyclopentadienes as New Chiral Diene Ligands for Asymmetric Rhodium-Catalyzed Arylation of <i>N</i>-Tosylarylimines,Monosubstituted C(1)-symmetric dicyclopentadienes as a new class of diene ligands have been developed for asymmetric arylation of N-tosylarylimines in excellent yields (98-99%) with high enantioselectivities (90-96%). The preparation of these diene ligands relied on an efficient lipase-catalyzed resolution as the key step.,10.1021/ol101531r,2010-08-12,0.5800129316620036
Tetrahedron,"Regiospecific synthesis of 9-ethoxy-4,5,6,8-tetramethoxy-1,3-dihydro-naphtho-(2,3-) furan-1-one: A key synthon of fredericamycin A",,10.1016/s0040-4039(00)95755-1,1987-01-01,0.5800080880016529
Synlett,Total Synthesis of Eleuthoside A; Application of Rh-Catalyzed Intramolecular Cyclization of Diazonaphthoquinone,"The first total synthesis of (±)-eleutherol and eleuthoside A, the natural cytotoxic substances extracted from medicinal Indonesian plant, is described. First, the synthesis of (±)-eleutherol has been ­accomplished in nine steps starting from bromo methoxy aldehyde with the aid of diazo-transfer chemistry approach. Second, a metal-­catalyzed intramolecular cyclization reaction of the corresponding ­diazonaphthoquinone led to the desired eleuotherol, which served as a precursor to eleuthoside A. Then, several glycosidation routes, using different glucosyl donors, were experimented to reach effective O-glycosidation of eleutherol. The only successful strategy involved Koenigs–Knorr glycosidation using peracetyl glycosyl bromide in the presence of Ag2O and quinoline. This strategy furnished our desired acetylated glycoside of β-configuration, regioselectively. Finally, deacetylation and successive separation of diastereomers were conducted to give eleuthoside A.",10.1055/s-0036-1589118,2017-11-03,0.5800068171972999
Tetrahedron,"Nitroketene dithioacetal chemistry. Part 2: Synthesis of novel 4-(alkylsulfanyl)-2-[1-nitromethylidene]-1,3-dithioles from the dipotassium salt of 2-nitro-1,1-ethylenedithiol",,10.1016/s0040-4039(03)01086-4,2003-05-28,0.5799980824839599
Tetrahedron,Seven-membered ring synthesis based on arene olefin cycloadditions: The total synthesis of (±)-Rudmollin,,10.1016/s0040-4039(00)84394-4,1986-01-01,0.5799979445581314
Tetrahedron,Stereoselective formation of a hydrindane ring system by anionic olefin cyclization. Trapping of the alkyllithium intermediate with electrophiles.,,10.1016/s0040-4039(00)84037-x,1986-01-01,0.579993770090637
Tetrahedron,"Unexpected pyrazolo[4,3-d][2,3]benzodiazepine synthesis from 1-(N,N-diaroyl)amino-4-phenyl-[1,2,3]triazol-5-yl-methyltriphenylphosphonium bromide via tandem phosphorylide formation and subsequent Dimroth-like rearrangement of the triazole ring",,10.1016/0040-4039(95)01034-f,1995-07-01,0.5799919462782591
Tetrahedron,"Unexpected Pyrazolo[4,3-d][2,3]benzodiazepine Synthesis from 1-(N,N-Diaroyl)amino-4-phenyl-[1,2,3]triazol-5-yl-methyltriphenylphosphonium bromide via Tandem Phosphorylide Formation and Subsequent Dimroth-like Rearrangement of the Triazole Ring",,10.1016/00404-0399(50)1034f-,1995-07-31,0.5799919462782591
Tetrahedron,Synthetic studies on dragmacidin D: synthesis of the left-hand fragment,,10.1016/j.tetlet.2008.10.020,2008-10-10,0.5799871600398253
Tetrahedron,Synthetic studies on apoptolidin: synthesis of the C1–C21 macrolide fragment,,10.1016/s0040-4039(01)01948-7,2001-12-01,0.5799871600398253
Tetrahedron,Synthetic studies on spongistatins: synthesis of the C29–C44 fragment,,10.1016/s0040-4039(00)00383-x,2000-04-01,0.5799871600398253
Tetrahedron,Synthetic studies towards the immunosuppressant FK-506 synthesis of the C10C34 fragment,,10.1016/s0040-4039(00)92267-6,1991-01-01,0.5799871600398253
Tetrahedron,"Synthetic studies of polyene macrolides, synthesis of a C29–37 fragment for amphotericin B and nystatin",,10.1016/s0040-4039(00)85554-9,1982-01-01,0.5799871600398253
Journal of Organic Chemistry,Divergent Route to Access Structurally Diverse 4-Quinolones via Mono or Sequential Cross-Couplings,A divergent route was developed to access 3-iodo- and 6-chloro-3-iodo-4(1H)-quinolones for further elaboration via mono and/or sequential Suzuki-Miyaura cross-coupling to generate novel and medicinally important 4(1H)-quinolones. Copper- and palladium-catalyzed cyanations were used to functionalize the 4-quinolone core further.,10.1021/jo1014504,2010-11-17,0.5799826825554606
Journal of Organic Chemistry,Synthesis of Fluorescent Ring-Fused 2-Pyridone Peptidomimetics,"Thiazolino fused 2-pyridone peptidomimetics are of significant biological importance due to their ability to interfere with adhesive fiber formation in uropathogenic Escherichia coli and oligomerization of amyloid fibers. We have developed an efficient synthetic route to fluorescent BODIPY analogues, with structural diversification from a key intermediate enabling introduction of C-2 substituents and late incorporation of the BODIPY moiety. A mild lithium halide mediated hydrolysis enabled preparation of peptidomimetic fluorophores with useful photophysical properties for further chemical biology applications.",10.1021/jo401844y,2013-10-25,0.5799814583405043
Synlett,"A Concise Synthesis of 6-Amino-6-deoxy-DNJ and 6-Amino-1,6-dideoxy-l-talonojirimycin","A concise and straightforward synthesis of two amino-DNJ derivatives, 6-amino-6-deoxy-DNJ and 6-amino-1,6-dideoxy-l-talonojirimycin is described from a commercial and cheap starting material. The methodology employed takes advantage of dia­stereoselective reductive amination to achieve the two non-natural iminosugars in three and five steps, respectively.",10.1055/s-0029-1219827,2010-04-15,0.5799799749893906
Angewandte Chemie International Edition,Design and Enantioselective Construction of Axially Chiral Naphthyl‐Indole Skeletons,"The first enantioselective construction of a new class of axially chiral naphthyl-indole skeletons has been established by organocatalytic asymmetric coupling reactions of 2-naphthols with 2-indolylmethanols (up to 99 % yield, 97:3 e.r.). This approach not only affords a new type of axially chiral heterobiaryl backbone, but also provides a new catalytic enantioselective strategy for constructing axially chiral biaryl scaffolds by making use of the C3-electrophilicity of 2-indolylmethanols.",10.1002/anie.201608150,2016-11-03,0.57997937097221
Angewandte Chemie International Edition,"Divergent and Efficient Syntheses of the <i>Lycopodium</i> Alkaloids (−)‐Lycojaponicumin C, (−)‐8‐Deoxyserratinine, (+)‐Fawcettimine, and (+)‐Fawcettidine",Four from one: The four title alkaloids (structures shown in blue box) have been synthesized by using a common versatile intermediate with a 6/5/5 tricyclic skeleton. This tricyclic intermediate could be easily assembled by using an intramolecular carbene addition/cyclization and a Dieckmann condensation/Tsuji-Trost allylation as key steps.,10.1002/anie.201306369,2013-09-02,0.5799758628884942
Journal of the American Chemical Society,An Exceptionally Short and Simple Enantioselective Total Synthesis of Pentacyclic Triterpenes of the β-Amyrin Family,"A new and very direct enantioselective total synthesis of members of the β-amyrin family of pentacyclic triterpenes has been developed starting with acylsilane 5, 2-propenyllithium, and cyclohexenylmethyl bromide 6, which were assembled to form tetraene 7 . Cationic cyclization of 7 and silylation afforded 8, which after vinyl triflate formation was cyclized via a Cu(I) intermediate (Scheme 2) to form the TBS ether of aegiceradienol 10, a versatile intermediate that is readily converted into natural β-amyrins such as β-amyrin ( 1 ) and oleanolic acid ( 2 ). The C(14)-diastereomer ( 13 ) of aegiceradienol was also synthesized from the C(14)-diastereomer of 8 using an intramolecular Stille reaction for the closure of ring D (Scheme 4).",10.1021/ja992411p,1999-10-08,0.5799755111826498
Organic Letters,"A Streamlined Synthesis for 2,3-Dihydroxyterephthalamides","[reaction: see text]. 2,3-Dihydroxyterephthalamides have been synthesized through a route that avoids the protection and deprotection of the phenol groups. The procedure allows for symmetric and unsymmetric amide linkages. This synthetic sequence significantly decreases the time and cost of preparation and increases the overall yield of this class of metal chelators.",10.1021/ol016253u,2001-08-10,0.5799653111936682
Tetrahedron,"Asymmetric synthesis of novel β-substituted β-methoxyacrylates bearing a chiral 1,2-cis-disubstituted cyclopropane substructure",,10.1016/s0040-4039(02)01677-5,2002-09-01,0.5799649702616224
Journal of the American Chemical Society,Enantioselective Synthesis of γ-Hydroxyenones by Chiral Base-Catalyzed Kornblum DeLaMare Rearrangement,"A cinchona-alkaloid catalyzed asymmetric Kornblum DeLaMare rearrangement has been developed. Thus, enantioenriched 4-hydroxyenones are prepared from dienes by a two-step sequence involving photochemical dioxygenation and chiral base-catalyzed desymmetrization of the resulting endoperoxides.",10.1021/ja065464x,2006-09-07,0.5799641969309347
Organic Letters,Expedient Synthesis of the α-<i>C</i>-Glycoside Analogue of the Immunostimulant Galactosylceramide (KRN7000),[Structure: see text] Key reactions in a concise synthesis of an alpha-C-galactosylceramide analogue of KRN7000 include a diastereoselective alkenylalane addition to an N-tert-butanesulfinyl imine and the use of an epoxidation/carbamate ring opening sequence to install the aminodiol stereotriad.,10.1021/ol0613057,2006-06-29,0.5799615972307678
Organic Letters,Chemical Synthesis of Cross-Linked Purine Nucleosides,"[reaction: see text] An efficient route to all of the possible cross-linked 2'-deoxypurines 1-3 has been developed by means of the Pd-mediated C-N bond formation in the key step. Utilizing this protocol, the synthesis of the first unnatural protected purine trimeric adduct 4 has been accomplished.",10.1021/ol990351m,2000-01-13,0.5799510957110064
Organic Letters,Allenyl Azide Cycloaddition Chemistry: Application to the Total Synthesis of (±)-Meloscine,"The pentacyclic alkaloid (±)-meloscine was prepared in 19 steps through a reaction sequence that features a putative azatrimethylenemethane intermediate, generated through cascade cyclization of an allenyl azide substrate, to deliver the core azabicyclo[3.3.0]octadiene substructure. Subsequent manipulation of the peripheral functionality then delivered (±)-meloscine.",10.1021/ol203463n,2012-01-13,0.5799468336461068
Organic Letters,"Short and Protecting-Group-Free Approach to the (−)-Δ<sup>8</sup>-THC-Motif: Synthesis of THC-Analogues, (−)-Machaeriol B and (−)-Machaeriol D","Friedel–Crafts alkylation of resorcinols with ( S )- cis -verbenol and subsequent cyclization allows the construction of the tetrahydrodibenzopyran core of (−)-Δ 8 -THC which is also found in other natural products in one step. Using a benzofuryl substituted resorcinol, followed by diastereoselective hydroboration and oxidative or reductive workup, directly provides (−)-machaeriol B and D in 42% and 43% overall yields. Bromoresorcinol as a coupling partner delivers Br–THC that can be applied for late-stage diversification by Suzuki–Miyaura cross-coupling to readily access (−)-Δ 8 -THC analogues.",10.1021/acs.orglett.8b01005,2018-04-27,0.5799448688039894
Organic Letters,Synthesis and Biological Evaluation of Himanimide C and Unnatural Analogues,"Recently isolated himanimide C (1) can be prepared via a short, flexible, and stereoselective synthesis using a copper-mediated tandem vicinal difunctionalization of dimethyl acetylenedicarboxylate (DMAD, 8) as a key step. The flexibility of the synthesis is exemplified by the preparation of new unnatural himanimide analogues in order to investigate the fungicidal potency of this new family. [structure: see text]",10.1021/ol047664o,2005-01-22,0.5799434132590298
Journal of Organic Chemistry,Total Synthesis of Leucascandrolide A:  A New Application of the Mukaiyama Aldol−Prins Reaction,"A total synthesis of the marine natural product leucascandrolide A has been completed. The titanium tetrabromide-mediated Mukaiyama aldol-Prins (MAP) reaction with aldehydes developed in our group provided a highly convergent and stereoselective method for assembling the core of the molecule. A new class of MAP reactions with acetals is introduced, and mechanistic considerations for both MAP methods are described. The total synthesis was completed by coupling of the side chain through two avenues: a known Still-Gennari olefination and a new Z-selective aldol/dehydroselenation reaction. Both procedures were highly selective and provided the natural product.",10.1021/jo070901r,2007-06-27,0.579942171463196
Tetrahedron,Protection of the internucleotidic bond after its synthesis. An approach to the synthesis of oligonucleotidic chains.,,10.1016/s0040-4039(01)94065-1,1972-01-01,0.5799417828222213
Organic Process Research & Development,Development of One-Pot Synthesis of New Antiarthritic Drug Candidate S-2474 with High <i>E</i>-Selectivity,"A one-pot synthesis of S-2474 was developed to overcome the problems of a large number of steps, low stereoselectivity, low yield, a large amount of waste, and severe reaction conditions. Aldol-type condensation of 3,5-di- tert -butyl-4-hydroxybenzaldehyde and N -ethyl-γ-sultam was carried out with LDA and then quenched with water. Dehydration proceeded under basic conditions, providing S-2474 directly as a single isomer on the benzylidene double bond. The reaction mechanism appears to involve a quinone methide intermediate. Environmental assessment of the development of this compound is also discussed in this paper.",10.1021/op800008w,2008-04-30,0.579939548209202
Synthesis,Ethyl 3-(1-Adamantyl)-2-diazo-3-oxopropanoate: Synthetic Use for the Preparation of Some Adamantane Derivatives,"(opens in new window) Buy Article (opens in new window) Permissions and Reprints (opens in new window) All articles of this category (opens in new window) The title compound was prepared by a diazo-transfer method, and utilized for synthesis of an adamantane-substituted ketene and heterocycles including 1,2, 3-triazole,1,2,3-thiadiazole, oxazole, and β-lactam derivatives. Fluorination of this compound was achieved by boron trifluoride promoted dediazotization to give the corresponding α-fluoro-β-oxo ester.",10.1055/s-1993-25944,1993-01-01,0.5799291026898262
Synthesis,Chemistry of 3-Hydroxypyridine Part 3: Synthesis of Substituted 3-[Fluoro(chloro)alkoxy]pyridines from Halo- or Amino-3-hydroxypyridines,All articles of this category The preparation of new substituted 3-[fluoro(chloro)alkoxy]-pyridines from halo- and amino-3-hydropxypyridines via difluorocarbene insertion or by addition of fluoroolefins is described.,10.1055/s-1990-26956,1990-01-01,0.5799256453217108
Tetrahedron,The chemistry of O-silylated ketene acetals: an efficientstereocontrolled synthesis of N-benzoyl L-daunosamine,,10.1016/s0040-4039(00)95946-x,1987-01-01,0.5799255939501591
Tetrahedron,Prostaglandin chemistry VI. Synthesis of 8-methoxycarbonylprostaglandins,,10.1016/s0040-4039(00)92582-6,1976-11-01,0.5799255939501591
Tetrahedron,Synthesis and chemistry of sesquibicyclo[2.2.2]octene and a tetradecacyclic-caged sesquibicyclo[2.2.2]octene,,10.1016/s0040-4039(98)01772-9,1998-10-01,0.5799255939501591
Synthesis,Synthesis and Chemistry of Dithiols,,10.1055/s-2001-831397,2004-08-05,0.5799255939501591
Tetrahedron,Silicon in organosulphur chemistry. Part 2. Synthesis of unsymmetrical disulphides,,10.1016/s0040-4039(00)99178-0,1989-01-01,0.5799255939501591
Tetrahedron,"Synthesis of (±)-isoretronecanol, (±)-curassanecine, (±)-heliotridane, (±)-tashiromine and (±)-5-epitashiromine via α-(N-carbamoyl)alkylcuprate chemistry",,10.1016/s0040-4039(02)01835-x,2002-10-01,0.5799255939501591
Tetrahedron,Silicon in organosulphur chemistry. Part 1. Synthesis of trisulphides,,10.1016/s0040-4039(00)99177-9,1989-01-01,0.5799255939501591
Tetrahedron,"The chemistry of phenalenium system. XII naphtho[1,8]tricyclo[4.1.0.02,7]Heptene. Synthesis and rearragement to pleiadiene",,10.1016/s0040-4039(01)95573-x,1973-01-01,0.5799255939501591
Tetrahedron,Chemistry of xanthorrhizol: synthesis of several bisabolane sesquiterpenoids from xanthorrhizol,,10.1016/j.tetlet.2006.11.051,2006-12-07,0.5799255939501591
Tetrahedron,Stereocontrolled synthesis of (±)-recifeiolide via organopalladium chemistry,,10.1016/s0040-4039(01)91511-4,1978-01-01,0.5799255939501591
Journal of Organic Chemistry,"Enantioselective Total Syntheses of Omuralide, 7-<i>epi</i>-Omuralide, and (+)-Lactacystin","An alkylidene carbene 1,5-CH insertion has been used as a key step in an enantioselective total syntheses of omuralide, its C7-epimer, and (+)-lactacystin. An additional noteworthy feature of the synthesis is the use of a novel oxidative deprotection procedure, utilizing DMDO, for the conversion of a late-stage benzylidene acetal into a primary alcohol and a secondary benzoate ester.",10.1021/jo7027695,2008-02-21,0.5799249412241082
Synlett,"A Convenient Synthesis of 1-(S)-[1’-(S)-(t-Butyloxycarbonylamino)-2’-phenylethyl]oxirane, a Versatile Intermediate for the Preparation of Hydroxyethylamine Based HIV Protease Inhibitors","All articles of this category A concise, stereocontrolled synthesis of N -protected (1 S ,1’ S)- α-aminoepoxides, important intermediates for the preparation of hydroxyethylamine dipeptide isosteres, beginning with α-aminoesters is described. α-aminoepoxide - hydroxyethylamine",10.1055/s-1995-5030,1995-06-01,0.5799198596292987
European Journal of Organic Chemistry,Synthesis of 1β-Methylcarbapenem Antibiotic Precursors by Cyclization Using π-Allylpalladium Complexes,"An efficient diastereoselective multi-step synthesis of bicyclic 1β-methylcarbapenem antibiotic precursors has been developed, starting from the commercially available 4-acetoxyazetidin-2-one 4. Chiral ruthenium catalysts are used in the hydrogenation step to control the β-stereochemistry at the 1-position, and a π-allylpalladium ring-closure strategy is used to form the functionalized carbapenem skeleton.",10.1002/(sici)1099-0690(199903)1999:3<621::aid-ejoc621>3.0.co;2-a,1999-03-01,0.5799184224679917
Organic Letters,Progress toward the Enantioselective Synthesis of Curcusones A–D via a Divinylcyclopropane Rearrangement Strategy,"We report our iterative efforts toward the divergent total syntheses of curcusones A-D via Suzuki coupling, intramolecular cyclopropanation, and a key divinylcyclopropane rearrangement. Progress of our synthesis was repeatedly challenged by the highly substrate-dependent cyclopropanation step, which we could ultimately overcome by judicious choice of substituents on the six-membered ring fragment.",10.1021/acs.orglett.9b03829,2019-11-25,0.5799165187369237
Journal of Organic Chemistry,"Toward Amide-Modified RNA:  Synthesis of 3‘-Aminomethyl-5‘-carboxy-3‘,5‘-dideoxy Nucleosides","Recent discovery of RNA interference has reinvigorated the interest in chemically modified RNA. Chemical approaches may be used to optimize properties of small interfering RNAs, such as thermal stability, cellular delivery, in vivo half-life, and pharmacokinetics. From this perspective, amides as neutral and hydrophobic internucleoside linkages in RNA are highly interesting modifications that so far have not been tested in RNA interference. Amides are remarkably good mimics of the phosphodiester backbone of RNA and can be prepared using a relatively straightforward peptide coupling chemistry. The synthetic challenge that has hampered the progress in this field has been preparation of monomeric building blocks for such couplings, the nucleoside amino acid equivalents. Herein, we report two synthetic routes to enantiomerically pure 3'-aminomethyl-5'-carboxy-3',5'-dideoxy nucleosides, monomers for preparation of amide-modified RNA. Modification of uridine, a representative of natural nucleosides, using nitroaldol chemistry gives the target amino acid in 16 steps and 9% overall yield. The alternative synthesis starting from glucose is somewhat less efficient (17 steps and 6% yield of 3'-azidomethyl-5'-carboxy-3',5'-dideoxy uridine), but provides easier access to modified nucleosides having other heterocyclic bases. The syntheses developed herein will allow preparation of amide-modified RNA analogues and exploration of their potential as tools and probes for RNA interference, fundamental biochemistry, and bio- and nanotechnology.",10.1021/jo060457c,2006-06-30,0.5799153016698809
European Journal of Organic Chemistry,Approaches to the Synthesis of a Water‐Soluble Carboxy Nitroxide,"Abstract The robust and diversely useful isoindoline nitroxide, 5‐carboxy‐1,1,3,3‐tetramethylisoindolin‐2‐yloxyl ( 1 ; CTMIO), has previously been synthesised in low‐to‐moderate yields from phthalic anhydride ( 3 ). Recent interest in its biological potential as a potent antioxidant and in other areas has seen an increased demand for its production. Herein, three new synthetic routes to CTMIO are presented and their efficiencies assessed. Two routes, via the nitrile 9 and the formyl compound 11 , derive from 5‐bromo‐1,1,3,3‐tetramethylisoindoline ( 6 ). The third approach starts from the readily accessible starting material, 4‐methylphthalic anhydride ( 12 ), and proceeds by a methylarene oxidation with potassium permanganate. The three new approaches yield CTMIO in comparable overall yields (16–18 %); however, the synthetic efficiency is most improved when employing the nitrile intermediate 9 .",10.1002/ejoc.201201551,2013-01-08,0.5799122684507995
Tetrahedron,An asymmetric synthesis (−)-epibatidine,"A Pd catalyzed desymmetrization of cis-3,6-dibenzoyloxy-2-cyclohexene and a Pd catalyzed cross-coupling constitute key reactions in a synthesis of the non-opioid analgesic (−)-epibatidine.",10.1016/0040-4039(96)01739-x,1996-10-01,0.5799090415473986
Journal of Organic Chemistry,"Synthesis of C-17-Functionalized Spongiane Diterpenes:  Diastereoselective Synthesis of (−)-Spongian-16-oxo-17-al, (−)-Acetyldendrillol-1, and (−)-Aplyroseol-14","The diastereoselective synthesis of spongiane diterpenes (-)-spongian-16-oxo-17-al 2, (-)-acetyldendrillol-1 15, and (-)-aplyroseol-14 16 has been completed efficiently via the common intermediate 14. Compound 14 was prepared in five synthetic steps from (+)-podocarp-8(14)-en-13-one 13, easily available from commercial (-)-abietic acid. The key steps in the syntheses were a regioselective reduction of a 1,4-dialdehyde unit, a one-pot acetalization-acetylation, and a translactonization. The synthesis of 15 and 16 has led us to a revision of the configuration at C-17 for natural (-)-acetyldendrillol-1 and a structural reassignment for aplyroseol-14. Thus, aplyroseol-14 16 presents an unprecedented delta-lactone-based structure for spongiane-type diterpenoids. A theoretical study including a series of ab initio calculations for the mechanism involved in the conversion of ester 22 into natural product 2 has also been carried out.",10.1021/jo026536f,2003-01-10,0.5799086796849495
Tetrahedron,"The first asymmetric synthesis of a 4-aryl-substituted 5-carboxy-3,4-dihydropyridin-2-one derivative",,10.1016/j.tetlet.2010.01.049,2010-01-21,0.5799066835312305
European Journal of Organic Chemistry,"Total Asymmetric Synthesis of Quinine, Quinidine, and Analogues via Catalytic Enantioselective Cascade Transformations","A catalytic asymmetric strategy for the total synthesis of quinuclidine natural products, which includes the completed enantioselective synthesis of the classical targets quinine and quinidine is disclosed. It is based on catalytic asymmetric cascade transformations, which paves the road for the synthesis of both enantiomers of the crucial C4 stereocenter with high enantioselectivity (up to 99 % ee ) in one pot. Next, developing a route to all possible stereoisomers of a common early‐stage intermediate sets the stage for the total synthesis of different enantiomers or epimers of quinine, quinidine and analogues with high selectivity.",10.1002/ejoc.201901003,2019-08-09,0.5799056848977245
European Journal of Organic Chemistry,Total Synthesis of the Marine Natural Product Parazoanthine F by Copper‐Mediated C–N Coupling,"Abstract The total synthesis of the marine natural product parazoanthine F from the sea anemone Parazoanthus axinellae is described. The key problem was the assembly of an N ‐styrylhydantoin moiety. It was possible to cleanly hydroxylate the benzylic position of the corresponding phenethyl unit by treatment with cerium ammonium nitrate. However, elimination to the alkene proved to be surprisingly difficult. The breakthrough came after optimizing the CuI/ N , N′ ‐dimethylethylenediamine‐mediated C–N coupling of a 2,2,4,6,7‐pentamethyl‐5‐sulfonyl‐dihydrobenzofuran‐protected arginine amide with p ‐methoxystyryl bromide under microwave conditions (70 °C, 200 W) in the presence of Cs 2 CO 3 . Our studies culminated in a short approach with an overall yield of about 12 %.",10.1002/ejoc.201500823,2015-08-25,0.5799055834855871
Tetrahedron,"Synthesis of enantiomerically pure all cis-2,3,6-trisubstituted piperidine: a silicon mediated total synthesis of (+)-carpamic acid",,10.1016/s0040-4039(02)01853-1,2002-10-01,0.5799053869644809
Tetrahedron,Synthetic studies on indole alkaloids. VI synthesis of tetrahydroakuammicine and dihydrocorynantheol via 2-(3-indolyl)-4-piperidones,,10.1016/s0040-4039(00)61666-0,1993-01-01,0.5799048349594567
Tetrahedron,Synthesis of new semi-synthetic dipodands and tripodands from naturally occurring polyether ionophores,,10.1016/j.tetlet.2008.06.116,2008-07-02,0.5799024936238775
Angewandte Chemie International Edition,"Collective Total Synthesis of Mavacuran Alkaloids through Intermolecular 1,4‐Addition of an Organolithium Reagent**","We report a synthetic endeavor towards the highly strained pentacyclic caged framework of the mavacuran alkaloids which culminated with the concise total synthesis of C-fluorocurine, C-profluorocurine, C-mavacurine, normavacurine, 16-epi-pleiocarpamine and taberdivarine H. We designed a strategy involving late-stage construction of the D ring by Michael addition of a vinylic nucleophile to a 2-indolyl acrylate moiety. While the intramolecular Michael addition did not succeed, we were able to perform a diastereoselective unusual intermolecular 1,4-addition of a functionalized vinyl lithium reagent to a readily accessible Michael acceptor with the assistance of the piperidine nitrogen atom through the formation of a complex as suggested by DFT computations. Final cyclization was achieved by nucleophilic substitution to form an ammonium intermediate. The first total syntheses of C-profluorocurine and C-fluorocurine were finalized by the dihydroxylation of C-mavacurine and a pinacol rearrangement, respectively.",10.1002/anie.202302461,2023-03-16,0.5799024704994438
Tetrahedron,Stereoselective synthesis of exocyclic alkenes via hydroboration-cross-coupling sequence,,10.1016/s0040-4039(00)92245-7,1992-04-01,0.5799002275329719
Organic Letters,First Total Syntheses of (±)-Penicillones A and B,"The first total syntheses of (+/-)-penicillones A (1) and B (2) have been accomplished from 2-methoxy-4,6-dimethylphenol (7) in 9 and 8 synthetic steps, respectively. Intramolecular Diels-Alder reaction of masked o-benzoquinone 8 and aqueous acid-catalyzed intramolecular aldol reaction are the key steps.",10.1021/ol702062p,2007-09-29,0.5798990895524911
Tetrahedron,Synthesis of novel zerumbone derivatives via regioselective palladium catalyzed decarboxylative coupling reaction: a new class of α-glucosidase inhibitors,,10.1016/j.tetlet.2013.11.110,2013-12-06,0.5798954786216477
Organic Letters,Total Synthesis of (−)-<i>N</i>-Methylwelwitindolinone C Isothiocyanate Based on a Pd-Catalyzed Tandem Enolate Coupling Strategy,"The highly stereocontrolled total synthesis of (-)-N-methylwelwitindolinone C isothiocyanate is described, which features the expeditious construction of a bicyclo[4.3.1]decane ring system by a palladium-catalyzed tandem enolate allylation/arylation reaction.",10.1021/acs.orglett.5b01952,2015-07-27,0.5798936590149188
Organic Letters,A Rapid Synthetic Approach to the ABCD Core of the <i>Stemona</i> Alkaloids,"A new Lewis acid-assisted Brønsted acid cascade approach for the stereoselective formation of the tetracyclic Stemona alkaloid skeleton is described in five steps from epoxide 15. Crucially, this tetracyclic product can be accessed as either C13 epimer, potentially serving as intermediates for the synthesis of a range of Stemona alkaloids.",10.1021/acs.orglett.8b03371,2018-12-18,0.5798815673111515
Tetrahedron,"Regioselective protection of xylose for efficient synthesis of arabino-α-1,3-xylosides",,10.1016/j.tetlet.2017.09.085,2017-09-30,0.579878781187182
Organic Letters,Modular Enantioselective Synthesis of an Advanced Pentahydroxy Intermediate of Antimalarial Bastimolide A and of Fluorinated and Chlorinated Analogues,"A short enantioselective catalytic synthesis of the key C15-C27 fragment of bastimolide A, a natural product showing promising antimalarial bioactivity, is disclosed. The strategic insertion of halogen atoms such as fluorine and chlorine by enantioselective organocatalytic halogenations allowed an excellent stereochemical control for the formation of complex acyclic fragments bearing up to four stereogenic centers. Furthermore, besides the formation of the 1,5,7,9,13-pentahydroxy fragment of the natural product, this strategy opens the route to the modulation of the bioactivity by halogenohydrins.",10.1021/acs.orglett.8b02213,2018-08-21,0.5798747204146294
Tetrahedron,A practical one-pot procedure for the synthesis of N–H isoquinolones,,10.1016/j.tetlet.2013.02.003,2013-02-09,0.5798703598673551
Tetrahedron,Total synthesis of (±)-forsythide aglucone dimethyl ester,,10.1016/s0040-4039(01)93210-1,1974-01-01,0.5798701866818468
Organic Letters,"Stereoselective Synthesis of Novel β,γ-Epoxyhydroxylamines and 4-Hydroxyalkyl-1,2-oxazetidines","A simple and efficient stereoselective synthesis of polysubstituted beta,gamma-epoxyhydroxylamines and 4-hydroxyalkyl-1,2-oxazetidines, based on the addition of alpha-lithiated aryloxiranes to nitrones and subsequent cyclization of the corresponding intermediates in a 4-exo-tet mode, is described.",10.1021/ol061256y,2006-08-01,0.579868364694571
Journal of Organic Chemistry,Applications of Organosulfur Chemistry to Organic Synthesis:  Total Synthesis of (+)-Himbeline and (+)-Himbacine,"Total syntheses of (+)-himbacine ( 1 ) and (+)-himbeline ( 2 ) are described. The synthesis involves the preparation of sulfone 38 and aldehyde 42 as single enantiomers followed by coupling of these compounds using a Julia−Lythgoe olefination. The preparation of sulfone 38 features an acid-promoted intramolecular Diels−Alder reaction of an α,β-unsaturated thioester while the synthesis of 42 features a Beak alkylation of piperidine 39 .",10.1021/jo970612a,1997-07-01,0.5798604425175385
Synthesis,Total Synthesis of RS-42358 and Analogs Using Lateral Lithiation,All articles of this category A short synthesis of the 5-HT 3 receptor antagonist RS-42358 was developed based on the condensation of lactone 2 with S 3-aminoquinuclidine. The position 2 analogs of RS-42358 were made by condensing various primary amines with lactone 2 . The key step in the synthesis of lactone 2 was lateral lithiation of diethyl amide 7 using n -BuLi in THF. lateral lithiation - 5-HT 3 - receptor antagonist - RS-42358,10.1055/s-2000-6321,2000-01-01,0.5798573982201085
Journal of the American Chemical Society,"General Approach to Epipolythiodiketopiperazine Alkaloids: Total Synthesis of (+)-Chaetocins A and C and (+)-12,12′-Dideoxychetracin A",A highly stereoselective and systematic strategy for the introduction of polysulfides in the synthesis of epipolythiodiketopiperazines is described. We report the first total synthesis of dimeric epitri- and epitetrathiodiketopiperazines.,10.1021/ja106869s,2010-09-24,0.5798546023717173
Tetrahedron,An improved synthesis of hydroxymethyl bipyridines,,10.1016/s0040-4039(00)00264-1,2000-04-01,0.5798530893579995
Organic Letters,Tandem Addition/Cyclization for Access to Isoquinolines and Isoquinolones via Catalytic Carbopalladation of Nitriles,"The first example of the palladium-catalyzed sequential nucleophilic addition followed by an intramolecular cyclization of functionalized nitriles with arylboronic acids has been achieved, providing an efficient synthetic pathway to access structurally diverse isoquinolines and isoquinolones. This methodology has also been successfully applied to the total synthesis of the topoisomerase I inhibitor CWJ-a-5 (free base).",10.1021/acs.orglett.6b03499,2016-12-27,0.5798476056401537
Angewandte Chemie International Edition,Organoclay Derivatives in the Synthesis of Macrocycles,"As an alternative to the rotaxane method, an organoclay can be used as a template for the efficient formation of macrocycles (ring in schematic representation) which are easily extracted from the clay interlayer space. The four-step synthesis involved preparation of a pillared clay from the dihydrochloride salt of p-xylylenediamine, insertion of neutral p-xylylenediamine into the pillared structure, reaction of the neutral p-xylylenediamine in the layers with isophthaloyl chloride and formation of the tetramide macrocycle, and extraction of the product from the clay.",10.1002/1521-3773(20011119)40:22<4286::aid-anie4286>3.3.co;2-d,2001-11-19,0.5798451192223014
Angewandte Chemie International Edition,Organoclay Derivatives in the Synthesis of Macrocycles,"As an alternative to the rotaxane method, an organoclay can be used as a template for the efficient formation of macrocycles (ring in schematic representation) which are easily extracted from the clay interlayer space. The four-step synthesis involved preparation of a pillared clay from the dihydrochloride salt of p-xylylenediamine, insertion of neutral p-xylylenediamine into the pillared structure, reaction of the neutral p-xylylenediamine in the layers with isophthaloyl chloride and formation of the tetramide macrocycle, and extraction of the product from the clay.",10.1002/1521-3773(20011119)40:22<4286::aid-anie4286>3.0.co;2-m,2001-11-16,0.5798451192223014
Journal of Organic Chemistry,"Divergent Total Syntheses of Gymnothelignan N, Beilschmin A, and Eupomatilones 1, 3, 4, and 7","A seven-step asymmetric total synthesis of gymnothelignan N is detailed in the current report. The approach is based on an early-stage one-carbon homologative lactonization reaction, which we recently revisited and modified to construct the core γ-butyrolactone motif with the requisite β,γ-vicinal stereogenic centers. By design, the utilization of the same chiral γ-butyrolactone intermediate permitted the rapid and effective divergent assembly of optically active eupomatilones 1, 3, 4, and 7 in five or six steps from commercially available materials. This represents one of the shortest and highest-yielding syntheses reported to date.",10.1021/acs.joc.1c03167,2022-02-28,0.5798445671769512
Journal of Organic Chemistry,Stereoselective Synthesis of a Sulfated Tetrasaccharide Corresponding to a Rare Sequence in the Galactofucan Isolated from <i>Sargassum polycystum</i>,"The first chemical synthesis of a highly sulfated tetrasaccharide 1, as the rare sequence in the galactofucan isolated from the brown alga Sargassum polycystum, was achieved in a convergent and stereoselective manner. The key features of the synthetic strategy include construction of multiple contiguous 1,2-cis glycosidic bonds and [2 + 2] assembly based on the rationally developed d-galactose building block 6. The synthesized oligosaccharides were fully characterized using a combination of coupled-HSQC and other 2D NMR techniques.",10.1021/jo500503r,2014-04-25,0.579844312442704
Tetrahedron,Scalable synthesis of sulfonium and selenonium peptides for selective methyllysine reader crosslinking,"Lysine methylation readers are an important class of proteins that bind site-specifically methylated proteins for downstream regulation. Chemical probes that crosslink lysine methylation readers are highly desired to investigate the proteins from cellular samples. We recently reported NleS + me2 (norleucine-ε-dimethylsulfonium) as dimethyllysine mimic selectively crosslinks corresponding methyllysine readers. Although the sulfonium tools exhibited great promise, the synthetic availability may limit broad applications. In order to incorporate the unnatural amino acid, l -Fmoc-NleSme-OH (Fmoc: fluorenyl methoxycarbonyl) was synthesized as an important building block for solid-phase peptide synthesis (SPPS) in the previous synthetic route. It took six steps with resolution of racemic mixture and radical mediated thiol-ene reaction. As a result, the synthesis was not scalable with only 4.4 % overall yield. Here we report a much-improved synthesis method so that diverse NleS + me2 peptides could be readily prepared. In addition, the new method enables preparation of selenonium peptides for methyllysine reader crosslinking. We thus believe this synthetic method will be widely used to prepare sulfonium and selenonium probes for site-selective crosslinking.",10.1016/j.tetlet.2024.155332,2024-10-21,0.5798172156001948
Organic Letters,An Orthogonally Protected Cyclitol for the Construction of Nigerose- and Dextran-Mimetic Cyclophellitols,"Cyclophellitols are potent inhibitors of exo- and endoglycosidases. Efficient synthetic methodologies are needed to fully capitalize on this intriguing class of mechanism-based enzyme deactivators. We report the synthesis of an orthogonally protected cyclitol from d-glucal (19% yield over 12 steps) and its use in the synthesis of α-(1,3)-linked di- and trisaccharide dextran mimetics. These new glycomimetics may find use as Dextranase inhibitors, and the developed chemistries in widening the palette of glycoprocessing enzyme-targeting glycomimetics.",10.1021/acs.orglett.1c03723,2021-11-30,0.579813962282585
Tetrahedron,An improved synthesis of methyl-labeled fatty acids,,10.1016/s0040-4039(00)92563-2,1976-11-01,0.5798130596069924
Synlett,"Novel Synthesis of 1,4-Dialkoxy-5,6,7,8-multisubstituted-2,3-dicyanonaphthalenes through Electron Transfer from Mg Metal and Efficient Development of New Naphthalocyanines","Novel methods for efficient synthesis of 1,4-diamyloxy-5,6,7,8-multisubstituted-2,3-dicyanonaphthalenes were successfully developed, starting from easily available 2,3-dicyanohydroquinone as a common single compound through only three steps, the first dibromination of 2,3-dicyanohydroquinone, the second Mitsunobu dialkylation of 2,3-dicyano-5,6-diboromo-1,4-hydroquinone, and the last Diels-Alder-type of cycloaddition between 1,4-alkoxy-2,3-dicyano-5,6-diboromobenzenes and multisubstituted furans, followed by reductive deoxygenation with Mg turning. The obtained 1,4-diamyloxy-5,6,7,8-multisubstituted-2,3-dicyanonaphthalenes were easily transformed into the corresponding naphthalocyanines in 20-45% yields which showed their λmax at 867-892 nm.",10.1055/s-0030-1259910,2011-03-15,0.5798101521460808
Tetrahedron,"Synthesis and Structure Confirmation Of Compound D, A Proinflammatory Arachidonate Metabolite",,10.1016/s0040-4039(00)99285-2,1989-01-01,0.5798075815655659
Journal of Organic Chemistry,Multigram Synthesis of Bicyclic α- and β-Prolines via Intramolecular C(sp<sup>3</sup>)–H γ-Lactamization as a Key Step,"A multigram synthesis of novel bicyclic α- and β-prolines was achieved via a C(sp 3 )–H amidation reaction as a key step. This step prepared seven bicyclic γ-lactams in high yield and stereoselective control. The scalable and reproducible protocol allowed the conversion of γ-lactams into α- and β-prolines in amounts up to 45 g under mild conditions, providing access to various isomeric bicyclic proline derivatives for potential use in drug design as medicinal building blocks.",10.1021/acs.joc.5c00452,2025-05-22,0.5798052480136505
Angewandte Chemie International Edition,"Total Synthesis of Cyanolide A in the Absence of Protecting Groups, Chiral Auxiliaries, or Premetalated Carbon Nucleophiles","No protection, no problem: The C2-symmetric macrodiolide cyanolide A is prepared in six steps from neopentyl glycol and allyl acetate by iridium-catalyzed double asymmetric allylation and a tandem cross-metathesis/oxa-Michael cyclization to form the substituted pyran. The synthesis is accomplished in the absence of any protecting groups, chiral auxiliaries, or premetalated carbon nucleophiles in fewer than half the steps of any prior approach.",10.1002/anie.201300843,2013-03-11,0.579804711186233
Organic Letters,Enantioselective Total Synthesis of Aperidine,"An efficient total synthesis of aperidine was accomplished using a Rh-catalyzed C-H insertion of a cis-dihydrobenzofuran ring. To circumvent the facile epimerization of the cis-dihydrobenzofuran ring, we designed and prepared the C-H insertion precursor diazoamide by Raines' protocol. Finally, the efficient incorporation of a guanidine group and mild deprotection conditions yielded this labile natural product.",10.1021/ol200728w,2011-04-22,0.5798004620607228
Journal of the American Chemical Society,"Total Synthesis of Viridicatumtoxin B and Analogues Thereof: Strategy Evolution, Structural Revision, and Biological Evaluation","The details of the total synthesis of viridicatumtoxin B (1) are described. Initial synthetic strategies toward this intriguing tetracycline antibiotic resulted in the development of key alkylation and Lewis acid-mediated spirocyclization reactions to form the hindered EF spirojunction, as well as Michael-Dieckmann reactions to set the A and C rings. The use of an aromatic A-ring substrate, however, was found to be unsuitable for the introduction of the requisite hydroxyl groups at carbons 4a and 12a. Applying these previous tactics, we developed stepwise approaches to oxidize carbons 12a and 4a based on enol- and enolate-based oxidations, respectively, the latter of which was accomplished after systematic investigations that revealed critical reactivity patterns. The herein described synthetic strategy resulted in the total synthesis of viridicatumtoxin B (1), which, in turn, formed the basis for the revision of its originally assigned structure. The developed chemistry facilitated the synthesis of a series of viridicatumtoxin analogues, which were evaluated against Gram-positive and Gram-negative bacterial strains, including drug-resistant pathogens, revealing the first structure-activity relationships within this structural type.",10.1021/ja506472u,2014-08-15,0.5797984762369583
Journal of Organic Chemistry,Thiazole-Based Stereoselective Routes to Leucine and Phenylalanine Hydroxyethylene Dipeptide Isostere Inhibitors of Renin and HIV-1 Aspartic Protease,"A new synthesis of hydroxyethylene dipeptide isosteres for Leu-Leu and Phe-Phe in their y-lactone form la and lb employing β-amino-a-hydroxy aldehydes with singly and doubly protected nitrogen has been developed. These key intermediates, which are available through the thiazole—aldehyde synthesis from L-leucine and L-phenylalanine, weee converted to alkanoates by Wittig olefination and reduction of the ethylenic double bond. Lactonization and stereoselective alkylation at C-2 of the resulting lactones completed the building up of the structural framework. Overall yields weee in the range 16—19% for la and 22—23% for lb. © 1995, American Chemical Society. All rights reserved.",10.1021/jo00129a037,1995-12-01,0.5797978166465582
Synlett,Methyl 4-Pentafluorosulfanylphenyl Sulfoximines,"A low-cost and high-yielding synthetic route towards methyl 4-pentafluorosulfanylphenyl sulfoximines from the corresponding sulfide has been developed. The intermediate N -cyano sulfoximine was converted into the corresponding N -(1 H )-tetrazole, and the N H-sulfoximine was modified by N-arylation and N-alkylation reactions.",10.1055/s-0034-1378936,2014-11-20,0.5797966213593214
Tetrahedron,An efficient synthesis of indol-3-yl benzonaphthyridines via copper(II) triflate-catalyzed heteroannulation,,10.1016/j.tetlet.2013.04.106,2013-05-03,0.5797955685564998
Tetrahedron,Synthesis of a perfluoroalkyl-substituted α-diimine by Sm-mediated reductive coupling,,10.1016/j.tetlet.2003.09.052,2003-10-01,0.5797942428584061
Synlett,"Conjugate Addition-Elimination Reactions as a Novel Synthetic Route to Dialkylated α,β-Unsaturated Diesters","All articles of this category The paper describes a novel synthetic route for mono- and dialkylation of dimethyl 2-phenylseleno fumarate 1 . The conjugate additions to 1 proceed regio- and stereoselectively. The subsequent oxidative eliminations of phenylseleno group provide a convenient procedure for the synthesis of the title compounds. dimethyl 2-phenylseleno fumarate - organolithiums - Michael addition - dimethyl 2,3-dialkyl fumarate",10.1055/s-1996-5306,1996-01-01,0.5797886879868331
Journal of Organic Chemistry,Synthesis of 1α-Hydroxyvitamin D<sub>5</sub> Using a Modified Two Wavelength Photolysis for Vitamin D Formation,"[reaction: see text] 1Alpha-hydroxyvitamin D5 (1) is a promising chemopreventive agent for breast cancer and is being developed as a drug. We report a synthesis for this vitamin D analogue which uses a photochemical method for the B-ring opening, leading to the conjugated triene system. The precursor 7-dehydrositosteryl acetate (4) obtained through a one-pot, five-step procedure, was completely free of the 4,6-diene isomer that usually forms in the 5,7-diene synthesis. The pre-vitamin isomer (11) was generated using a modified two-wavelength photolysis procedure that increases the yield for this step more than 3-fold compared to classically used photolysis. The 1alpha-hydroxylation step was performed on the 3-triethylsilyl-trans-vitamin D5 (17) obtained via the sulfur dioxide adduct of cis-vitamin D5, in an overall yield of 48%. Photoisomerization and deprotection completed the synthesis.",10.1021/jo050853f,2005-08-12,0.5797866529869841
Synlett,Synthesis of 3-Nitro-1<i>H</i>-indole-2-carboxylic Acid Ethyl Ester Derivatives from Baylis-Hillman Adducts,A simple and direct synthesis of 3-nitro-1H-indole-2-carboxylic acid ethyl ester derivatives from acetylated Baylis-Hillman adducts of 2-nitrobenzaldehydes is described.,10.1055/s-2005-868499,2005-01-01,0.5797861125599937
Synthesis,Synthesis of C<sub>6</sub>F<sub>5</sub>-Substituted Aminoethanols via Acetate Ion Mediated C<sub>6</sub>F<sub>5</sub>-Group Transfer Reaction,"A new approach for the synthesis of N-(pentafluorophen­ylmethyl)aminoethanols is developed. The method includes alkyl­ation of imines with 2-tris(pentafluorophenyl)silyloxyethyl triflate, prepared from ethylene oxide and (C6F5)3SiOTf, to give 2-silyloxyethyliminium ions. Their treatment with sodium acetate induces C-C bond formation proceeding as transfer of the C6F5 group from the five-coordinate silicate intermediate to the iminium center.",10.1055/s-2006-926278,2006-01-01,0.5797773561944775
Organic Letters,A Novel and Selective Fluoride Opening of Aziridines by XtalFluor-E. Synthesis of Fluorinated Diamino Acid Derivatives,The selective introduction of fluorine onto the skeleton of an aminocyclopentane or cyclohexane carboxylate has been developed through a novel and efficient fluoride opening of an activated aziridine ring with XtalFluor-E. The reaction proceeded through a stereoselective aziridination of the olefinic bond of a bicyclic lactam and regioselective aziridine ring opening with difluorosulfiliminium tetrafluoroborate with the neighboring group assistance of the sulfonamide moiety to yield fluorinated diamino acid derivatives. The method based on the selective aziridine opening by fluoride has been generalized to afford access to mono- or bicyclic fluorinated substances.,10.1021/acs.orglett.5b00182,2015-02-16,0.5797743102387533
Synlett,Asymmetric Synthesis of α- and β-Benzylhydroxy-γ-butyrolactones,"Herein we describe a new asymmetric synthesis of α-benzyl-α-hydroxy-γ-butyrolactone, a core building block of new HIV-1 protease inhibitors containing a tertiary alcohol in the transition-state mimic. Immediate access to β-benzyl-β-hydroxy-γ-butyro-lactone is also possible from a common intermediate. Both lactones are useful building blocks in their own right.",10.1055/s-0029-1218529,2009-11-30,0.5797736540807864
Tetrahedron,Stereoselective synthesis of (−)-8-epi-swainsonine starting with a chiral aziridine,,10.1016/j.tetlet.2012.11.087,2012-12-08,0.5797728274201902
European Journal of Organic Chemistry,Versatile Domino Rearrangement of Diphenylhomobenzoquinone Epoxides Induced by CF<sub>3</sub>SO<sub>3</sub>H,"Abstract CF 3 SO 3 H‐catalyzed reaction of 5‐alkyl‐( R )‐substituted diphenylhomobenzoquinone epoxides (R = Me, i Pr, t Bu) provided indenoquinones, a cyclopenta[ b ]chromene‐2‐carbaldehyde, and furan‐3(2 H )‐ones through novel cationic domino rearrangements depending on the R substituents. The mechanisms of these reactions were described by a combination of various key steps involving (i) transannular cyclization of the endo ‐phenyl group, (ii) epoxide and cyclopropane ring opening, (iii) ring contraction of the original quinone frame, (iv) dehydration and intramolecular S E 2/S N 2‐Ar cyclization, as well as (v) possible pseudopericyclic cheletropic decarbonylation.",10.1002/ejoc.201200455,2012-06-14,0.5797658222324777
Organic Letters,Asymmetric Synthesis of Chiral Acyclic Purine Nucleosides Containing a Hemiaminal Ester Moiety via Three-Component Dynamic Kinetic Resolution,"An efficient route to construct chiral acyclic purine nucleosides containing a hemiaminal ester moiety is reported via three-component dynamic kinetic resolution of purines, aldehydes, and acid anhydrides. The procedure provides diverse chiral acyclic purine nucleoside analogues in a regioselective manner with good yields (up to 93% yield) and excellent enantioselectivities (up to 95% ee). Furthermore, the chiral (acyloxyalkyl)-5-fluorouracil could also be generated as a potential prodrug of 5-fluorouracil.",10.1021/acs.orglett.8b00135,2018-01-26,0.5797657690536062
Synthesis,One-Pot Synthesis of Imidazopyridine Derivatives,"Two highly efficient and general one-pot annulation reactions are described for the synthesis of imidazopyridine derivatives (IPs). The two procedures are complementary to each other: Whereas the first one allows the production of simpler IPs, the second leads to IPs with functionalized imidazole moiety. Both methodologies consist of an activation step, which raises the electrophilicity of the N-heterocyclic starting material (i.e., quaternarization of the N-heterocycle), followed by a cascade reaction involving nucleophilic addition, substitution, rearrangement, and oxidation steps. These methodologies can be used in the synthesis of a library of drug-like molecules.",10.1055/s-2007-1000936,2008-04-25,0.5797640255109798
Synlett,"Catalytic Asymmetric Synthesis of (<i>R</i>)-(-)-Calycotomine, (<i>S</i>)-(-)-Salsolidine and (<i>S</i>)-(-)-Carnegine","A simple and efficient procedure for a synthesis of isoquinoline alkaloids is described. The key step of the synthesis was a hydrocyanation of 6,7-dimethoxy-3,4-dihydroisoqunoline giving the corresponding 1-cyano-1,2,3,4-tetrahydroisoquinoline. The asymmetric Strecker reaction was accomplished in high yield and high enantiomeric excess using Jacobsen's thiourea-containing ­catalyst. The 1-cyanoisoquinoline thus obtained was transformed to natural products, (R)-(-)-calycotomine, (S)-(-)-salsolidine and (S)-(-)-carnegine.",10.1055/s-2006-941586,2006-06-01,0.5797525716243251
Synthesis,"Synthesis of the Marine Compound (2<i>R</i>,5<i>Z</i>,9<i>Z</i>)-2-Methoxyhexacosa-5,9-dienoic Acid via a Lipase-Catalyzed Resolution and a Novel O-Alkylation Protocol",The title compound has been synthesized by a facile route starting from 4-pentyn-1-ol. The enantioselectivity was attained by a strategy involving a lipase-catalyzed acetylation of a solid-phase immobilized long chain α-hydroxy acid. Another important feature of the synthesis was the formulation of an efficient HgO-catalyzed O-methylation of the α-hydroxy acids which proceeded without any racemization. The alkylation protocol was also highly efficient for selective mono-methylation/benzylation of symmetrical diols.,10.1055/s-2004-815963,2004-01-01,0.579750965265592
Organic Letters,Selective Lewis Acid Catalyzed Assembly of Phosphonomethyl Ethers: Three-Step Synthesis of Tenofovir,"Described herein is a novel Lewis acid catalyzed rearrangement-coupling of oxygen heterocycles and bis(diethylamino)chlorophosphine that provides direct formation of the phosphonomethyl ether functionality found in several important antiretroviral agents. A wide range of dioxolanes and 1,3-dioxanes may be employed, furnishing the desired products in good yield. The utility of this method is demonstrated in a novel synthesis of tenofovir, an antiretroviral drug used in the treatment of HIV/AIDS and hepatitis B.",10.1021/ol503612h,2015-02-09,0.5797505190849735
Organic Letters,"New Synthetic Strategy toward Pyridine-Based Ligands for Supramolecular Chemistry Utilizing 2,6-Bis(trimethyltin)pyridine as the Central Building Block","2,6-Bis(trimethyltin)pyridine was synthesized in high yields and multigram quantities and used for Stille-type coupling procedures to prepare 2,2‘-bipyridines, 5,5‘ ‘-dimethyl-2,2‘:6‘,2‘ ‘-terpyridine, and 4,6-bis(5‘ ‘-methyl-2‘ ‘,2‘-bipyrid-6‘-yl)-2-phenylpyrimidine.",10.1021/ol990808s,1999-08-31,0.5797421619516803
Organic Process Research & Development,An Improved Process for the Synthesis and Isolation of (<i>S</i>)-<i>N</i>-(1-Phenylethyl)hydroxylamine,"A three-step, single-solvent telescoped process amenable to the large-scale manufacture of ( S )- N -(1-phenylethyl)hydroxylamine p -toluenesulfonic acid salt is reported. This synthetic protocol has been applied to the preparation of other chiral hydroxylamines.",10.1021/op800230f,2008-12-03,0.5797411780227271
Organic Letters,"Organocatalytic, Enantioselective Synthesis of VNI: A Robust Therapeutic Development Platform for Chagas, a Neglected Tropical Disease","VNI is a potent inhibitor of CYP51 and was recently shown to achieve a parasitological cure of mice infected with T. cruzi in both acute and chronic stages of infection. T. cruzi is the causative parasite of Chagas disease, a neglected tropical disease. The first enantioselective chemical synthesis of VNI (at a materials cost of less than $0.10/mg) is described. Furthermore, the key enantioselective step is performed at the 10 g scale.",10.1021/ol303092v,2012-12-07,0.5797409667450122
Tetrahedron,A one-pot stereoselective synthesis of novel polyfunctionalized imidazolidines,,10.1016/j.tetlet.2013.08.029,2013-08-15,0.5797405116631678
Tetrahedron,"An efficient synthesis of pyrroles by a one-pot, three-component condensation of a carbonyl compound, an amine and a nitroalkene in a molten ammonium salt",,10.1016/s0040-4039(03)00439-8,2003-03-01,0.5797369125569019
Organic Letters,Efficient Preparation of Terminal Conjugated Dienes by Coupling of Dienol Phosphates with Grignard Reagents under Iron Catalysis,An efficient new route to prepare stereoselectively terminal conjugated dienes by coupling Grignard reagents and dienol phosphates in the presence of Fe(acac)3 is described. The synthetic utility of this new iron-catalyzed procedure is illustrated by the synthesis of the pheromone of Diparopsis castanea according to a very expeditious strategy.,10.1021/ol800816f,2008-05-14,0.5797302477136469
Tetrahedron,Single-flask polyfunctionalization of the imidazole ring; a streamlined route to the antitumor agent carmethizole,,10.1016/s0040-4039(00)61074-2,1992-09-01,0.5797294293974699
Tetrahedron,"Efficient total synthesis of pentosidine, an advanced glycation endproduct",,10.1016/s0040-4039(99)00204-x,1999-03-01,0.5797230529987606
Tetrahedron,Asymmetric synthesis of anti-convulsive drug (S)-Vigabatrin®,,10.1016/s0040-4039(98)01324-0,1998-08-01,0.5797217252064698
Tetrahedron,Asymmetric synthesis of 2-amino-1-arylethanols by catalytic asymmetric hydrogenation,,10.1016/s0040-4039(01)93523-3,1979-01-01,0.579719038320547
Angewandte Chemie International Edition,Corrigendum: A Biosurfactant‐Inspired Heptapeptide with Improved Specificity to Kill MRSA,,10.1002/anie.201703383,2017-05-08,0.5797148816165373
Tetrahedron,A novel regioselective synthesis of 4-substituted tropones,,10.1016/s0040-4039(00)94657-4,1990-01-01,0.5797145183772157
Journal of Organic Chemistry,"Dipolar Cycloaddition of Ethyl Isocyanoacetate to 3-Chloro-2-(methylthio)/2-(methylsulfonyl)quinoxalines:  Highly Regio- and Chemoselective Synthesis of Substituted Imidazo[1,5-<i>a</i>]quinoxaline-3-carboxylates","An efficient route for regio- and chemoselective synthesis of substituted 3-(carboethoxy)imidazo[1,5-a]quinoxalines and novel diimidazo[1,5-a:5',1'-c]quinoxalines via base-induced cycloaddition of ethyl isocyanoacetate to unsymmetrically substituted 3-chloro-2-(methylthio)/2-(methylsulfonyl)quinoxalines has been reported.",10.1021/jo070590k,2007-06-01,0.5797138842125654
Tetrahedron,An aldehyde synthesis utilizing the thiazole ring system.,,10.1016/s0040-4039(01)87533-x,1971-01-01,0.5797104902496931
Organic Letters,Synthesis of the Aminocyclitol Core of Jogyamycin via an Enantioselective Pd-Catalyzed Trimethylenemethane (TMM) Cycloaddition,"The use of β-nitroenamines as a new class of acceptors in the enantioselective Pd-catalyzed trimethylenemethane cycloaddition afforded differentiated 1,2-dinitrogen bearing cyclopentanes with three contiguous stereocenters. The utility of these acceptors was demonstrated with the efficient construction of the core of jogyamycin and aminocyclopentitols. Further elaboration of the cycloadducts provided a concise synthetic approach toward joygamycin.",10.1021/acs.orglett.8b01518,2018-06-25,0.5797103662035873
Organic Letters,Total Synthesis of Paecilomycin B,"Starting from the glucose-derived δ-lactone and the functionalized aryl bromide, the first total synthesis of naturally occurring paecilomycin B was achieved via functionalized aryl-β-C-glycoside synthesis using 2,4,6-triisopropylphenyllithium under Barbier-type reaction conditions and ring-closing metathesis as the key steps.",10.1021/acs.orglett.5b00983,2015-05-04,0.5797071824655627
Tetrahedron,Synthesis via oxazolines IX. An asymmetric synthesis of 2-methoxy and 2-chloroalkanoic acids,,10.1016/s0040-4039(01)91946-x,1974-01-01,0.579699978026263
Tetrahedron,Efficient asymmetric synthesis of anti-aldols from bornanesultam derived boryl enolates,,10.1016/s0040-4039(00)79339-7,1993-07-01,0.5796981241669733
Tetrahedron,"An efficient synthesis of bislactone skeleton leading to d,l-canadensolide",,10.1016/s0040-4039(00)85792-5,1982-01-01,0.5796930250611877
Tetrahedron,"A novel synthesis of thiophenes from allenic sulfones involving α,β-unsaturated sulfines as intermediates",,10.1016/s0040-4039(00)79399-3,1991-07-01,0.5796921480795425
Tetrahedron,A Synthesis of β-necrodol via a palladium catalyzed reductive enyne cyclization,,10.1016/s0040-4039(00)80263-4,1988-01-01,0.579686742953537
Tetrahedron,"Asymmetric synthesis of β′-amino-α,β-enones via addition of α,β-unsaturated ketone-derived enolates to chiral N-phosphonyl imines",,10.1016/j.tetlet.2014.03.005,2014-03-16,0.5796835676791388
European Journal of Organic Chemistry,Chemical Synthesis of Ketopentose‐5‐phosphates,"A chemical synthesis of ketopentose‐5‐phosphates that are involved in the pentose phosphate pathway has been developed. The ketopentose phosphates, d ‐ribulose‐5‐phosphate and d ‐xylulose‐5‐phosphate, were prepared in five steps starting from known intermediates. Starting from readily available d ‐aldopentoses, reduction of the corresponding furanose derivatives gave key intermediates in the form of aldopentitols. Selective phosphorylation, oxidation, and deprotection provided the target molecules. This chemical synthesis makes such ketopentose phosphates readily available, and as a result they could be used as assay substrates for mechanistic studies. Since the pentose phosphate pathway is important in cancer‐cell metabolism, this synthetic approach provides an opportunity for preparing potential enzymatic inhibitors for use in drug development. To further extend this synthetic approach, a different protecting group (a trityl group) was used for the synthesis of the two parent ketopentoses ( d ‐ribulose and d ‐xylulose) in a similar manner.",10.1002/ejoc.201601639,2017-02-03,0.5796808765873097
Journal of Organic Chemistry,Total Synthesis of (±)-Sacidumlignan D,"The first total synthesis of (±)-sacidumlignan D featuring a Zn-mediated Barbier reaction and reverse Wacker oxidation to form the key γ-lactone, its diastereoselective α-methylation followed by reduction cyclization, was documented.",10.1021/jo1025749,2011-03-09,0.5796771152830031
Tetrahedron,"Concise asymmetric synthesis of (5S, 6S)- aeginetolide and (5S)- dihydroactinidiolide",,10.1016/s0040-4039(00)96368-8,1987-01-01,0.5796708896622539
Tetrahedron,Concise asymmetric synthesis of (−)-herbertenediol,,10.1016/s0040-4039(02)02440-1,2003-01-01,0.5796708896622539
Tetrahedron,A concise asymmetric synthesis of (−)-untenone A,,10.1016/0040-4039(95)00177-e,1995-03-01,0.5796708896622539
Tetrahedron,Concise asymmetric synthesis of dysidiolide,,10.1016/s0040-4039(00)00078-2,2000-03-01,0.5796708896622539
European Journal of Organic Chemistry,<i>C</i><sub>4</sub>‐Symmetric Alkoxyresorcin[4]arene Triflates: The Use of Palladium‐Catalyzed Reactions in the Synthesis of Axially Chiral Derivatives with Amino‐ and/or Alkoxy‐Substituents,"Abstract The conversion of axially chiral tetraalkoxyresorcin[4]arenes (cyclochiral resorcinarenes) into the related tetrakis(triflates) in high yields is described; this provides an efficient source of chiral materials for use in palladium‐catalyzed transformations, including the reductive removal of triflate groups and the synthesis of compounds that are formally derived from 3‐aminophenol, providing axially chiral derivatives that are nitrogen‐substituted on the upper rim.",10.1002/ejoc.201100122,2011-04-13,0.5796692951204957
Synlett,New Dephenylated Analogues of (–)-Goniofufurone: Optimization of Synthesis from l-Xylose,"Abstract Natural products containing highly oxygenated furanofuranone fragments are known for their potent biological activity, but also for their challenging total synthesis. In this study, the synthesis of five novel dephenylated (–)-goniofufurone analogues was completed and their cytotoxic activity against eight malignant and one normal human cell line was evaluated. Compared with previous syntheses of similar analogues, the synthesis was carried out starting from l-xylose, resulting in improved yields and a reduced number of synthetic steps for three divergent intermediates.",10.1055/a-2352-9691,2024-06-25,0.5796676034358114
Tetrahedron,Studies on the Synthesis of Olivin: Diastereoselective Synthesis of a Functionalized D-Fucose Derivative,,10.1016/s0040-4039(00)81890-0,1983-01-01,0.5796669646711423
Journal of Organic Chemistry,Enantioselective Synthesis of (−)-Wikstromol Using a New Approach via Malic Acid,"The total synthesis of (-)-wikstromol, a bioactive alpha-hydroxylated lactone lignan, from natural malic acid using a consecutive alkylation strategy is presented. First, alkylation of a malic acid ester provided the monobenzyl derivative, which was then converted to an alpha-substituted dioxolanone. This derivative was reacted in a second alkylation step to a double benzylated dioxolanone, which was transformed to bis-O-benzyl-protected (-)-wikstromol and subsequently to the natural product. Only six steps were required to produce wikstromol in 30% overall yield. A second approach from malic acid, the double alkylation of dienolates from 5-oxo-1,3-dioxolan-4-yl acetic acid derivatives, was not successful. No reaction conditions were found to afford the dienolates. Instead, rapid fragmentation of the dioxolanones to fumaric acid derivatives and pivalaldehyde occurred even at -105 degrees C, and aldol reaction products with good stereoselectivity were formed. The relative configuration of the major isomer was determined by X-ray structure analysis. By comparison of NMR data it is shown that a previous assignment of the configuration of one of the described aldol products was incorrect.",10.1021/jo001547z,2001-03-06,0.5796662605128408
Tetrahedron,Asymmetric enolate alkylation via templation with chiral synthetic receptors,,10.1016/j.tetlet.2003.11.002,2003-12-04,0.5796597425820339
Tetrahedron,A new method for enol lactone synthesis by a Michael addition/cyclization sequence,,10.1016/s0040-4039(03)00147-3,2003-02-01,0.5796562871648959
Tetrahedron,"Synthesis of the Hypoxia-Inducible Factor-2α (HIF-2α) Inhibitor, 3-[(1S,2S,3R)-2,3-Difluoro-1-hydroxy-7-methylsulfonylindan-4-yl]oxy-5-fluorobenzonitrile (PT2977, Belzutifan); Efficient Replication of Established Approaches",,10.1016/j.tetlet.2023.154691,2023-08-11,0.5796558175486735
Journal of Organic Chemistry,Asymmetric Synthesis of <scp>d</scp>-<i>ribo</i>-Phytosphingosine from 1-Tetradecyne and (4-Methoxyphenoxy)acetaldehyde,"An asymmetric synthesis of d-ribo-phytosphingosine (1) was achieved by utilizing the ProPhenol (12)-catalyzed alkynylation of unsaturated aldehyde 8 to afford allylic propargylic alcohol (S)-6 followed by asymmetric epoxidation and opening of propargylic epoxy alcohol anti-5 with NaN(3)/NH(4)Cl. Deprotection and reduction of the resulting acyclic azide 3 then gave 1. Alkyne-azide 3 was subjected to an intramolecular click reaction, generating a bicyclic triazole, which was found to have unexpected vicinal coupling constants. Application of the advanced Mosher method verified the configurations of the three contiguous stereogenic centers of 1. An alkynyl azide analogue of 1, which may be useful as a glycosyl acceptor in the synthesis of alpha-galactosylceramide derivatives, was also readily prepared by this route.",10.1021/jo100707d,2010-06-07,0.5796549157438993
Organic Letters,Straightforward Synthesis of Dihydrobenzofurans and Benzofurans from Arynes,"Synthesis of dihydrobenzofurans was achieved by a route involving the insertion of arynes into formamides followed by trapping with zinc enolates of α-chlorinated methines. Benzofurans were generated from dihydrobenzofurans having a ketone group via the addition of an ethyl anion, the retro-aldol type reaction, and the elimination of an amino group.",10.1021/ol4017063,2013-07-16,0.5796536669132009
Synlett,"Synthesis of a Ceramide Sphingolipid as a Potential Sex Pheromone of the Hair Crab<i>Erimacrus isenbeckii</i>Using Butane-2,3-diacetal Desymmetrised Glycolic Acid Building Blocks","A stereoselective synthesis of a ceramide sphingolipid as a potential sex pheromone of the hair crab Erimacrus isenbeckii is reported using diastereoselective alkylation and aldol reactions of butane-2,3-diacetal (BDA) desymmetrised glycolic acid building blocks as the key synthetic steps. © Georg Thieme Verlag Stuttgart.",10.1055/s-2005-862361,2005-01-01,0.57965258136615
Organic Process Research & Development,"Development of HIV-Integrase Inhibitor S-1360: Selection of the Protecting Group on the 1,2,4-Triazole Ring","HIV-integrase inhibitor S-1360 was synthesized by Claisen-type reaction of 5-(4-fluorobenzyl)-2-furyl methyl ketone with N-protected 1 H -1,2,4-triazole-3-carboxylate. The protecting group on the triazole ring is essential for the reaction to proceed. Tetrahydropyranyl and 1-methoxy-1-methylethyl groups were examined for manufacturing S-1360 on a large scale. High throughput and a convenient procedure were realized by using the 1-methoxy-1-methylethyl group.",10.1021/op700116y,2007-10-10,0.5796487479346429
Journal of the American Chemical Society,Total Synthesis of Acoapetaludine A Enabled by a Rhodium-Catalyzed Domino Cyclization,"A rhodium-catalyzed asymmetric domino cyclization was developed, which enables the efficient assembly of highly strained bridged tricyclic scaffolds. Taken together with a deprotection/retro-aldol/intramolecular Mannich reaction cascade and a diastereocontrolled intramolecular Diels–Alder cycloaddition, the first total synthesis of C 20 -diterpenoid alkaloid acoapetaludine A has been achieved in a concise and practical manner.",10.1021/jacs.5c18189,2025-12-16,0.5796457932944755
Organic Letters,Synthesis of the ABC Tricyclic System of Daphnicyclidin A,"A substrate-stereocontrolled synthesis of the ABC tricyclic system of daphnicyclidin A is developed. The key reactions include an efficient tandem N-allylation–S N 2′ reaction to assemble 2,3,4- cis trisubstituent pyrrolidine ring C and two intramolecular Horner–Wadsworth–Emmons reactions to construct cycloheptanone ring A and piperidine ring B.",10.1021/acs.orglett.7b00230,2017-03-15,0.5796457695292236
Synlett,"Stereocontrolled Synthesis of (1<i>R</i>,3<i>R</i>,4<i>S</i>)- and (1<i>S</i>,3<i>R</i>,4<i>S</i>)-3,4-diaminocyclopentanols","All articles of this category Cis - syn and cis - anti -3,4-diaminocyclopentanols have been synthesized from cyclopentadiene in eight steps. The key transformations involved construction of benzyl ether protected cis -diazidocyclopentanols, and sequential reduction and hydrogenolysis to the unprotected diaminocyclopentanols. stereocontrolled synthesis - vicinal diamine - diaminocyclopentanol - diazide reduction - debenzylation",10.1055/s-1999-2644,1999-04-01,0.5796436381445829
Journal of Organic Chemistry,A Highly Convergent Synthesis of a Complex Oligosaccharide Derived from Group B Type III <i>Streptococcus</i>,"An efficient synthesis of a heptasaccharide derived from group B type III Streptococcus carrying an artificial spacer (1) is described. Rapid assembly of a protected heptasaccharide (16a) is accomplished from readily available building blocks 2-5 without a single protecting group manipulation between glycosylation steps. The synthetic strategy may be applied to the assembly of other branched complex oligosaccharides. The deprotected heptasaccharide 1 was coupled to a poly[N-(acryloyloxy)succinimide, and the resulting material will be used for the development of an ELISA assay to detect antibodies against GBS, type III in pregnant women.",10.1021/jo001477w,2001-03-22,0.5796405627821793
Journal of the American Chemical Society,Unconventional Fragment Usage Enables a Concise Total Synthesis of (−)-Callyspongiolide,An asymmetric synthesis of (-)-callyspongiolide is described. The route builds the macrolide domain atypically from a disaccharide and a monoterpene without passing through a seco-acid. Chiral iridium catalysis selectively joins fragments. Subsequent degradation of an imbedded butyrolactone via perhemiketal fragmentation affords a stereo- and regio-defined homoallylic alcohol that is engaged directly in a carbonylative macrolactonization. Further elaboration of the polyunsaturated appendage provides the natural product in a particularly direct and flexible manner.,10.1021/jacs.7b13591,2018-01-13,0.579634875981346
Angewandte Chemie International Edition,Enantioselective Total Synthesis of (−)‐Cephalotanin B,"Cephalotaxus diterpenoids are attractive natural products with intriguing molecular frameworks and promising biological features. As a structurally unusual member, (-)-cephalotanin B possesses an extraordinarily congested heptacyclic skeleton, three lactone units, and nine consecutive stereocenters. Herein, we report an enantioselective total synthesis of (-)-cephalotanin B based on a divergent asymmetric Michael addition reaction, a novel Pauson-Khand/deacyloxylation process discovered in the development of a second-generation stereoselective Pauson-Khand reaction protocol, and an epoxide-opening/elimination/dual-lactonization cascade to construct the challenging propeller-shaped A-B-C ring system as key transformations.",10.1002/anie.202312599,2023-10-12,0.5796336354185939
Angewandte Chemie International Edition,Divergent Total Synthesis of the Antimitotic Agent Leiodermatolide,"Subtle but distinctive: The stereostructure of the biologically highly promising antimitotic agent leiodermatolide was uncertain. A short, efficient, and flexible total synthesis based on ring-closing alkyne metathesis as the key step has now solved the puzzle. Subtle differences in the 1H NMR spectra of the structure shown and the conceivable isomer proved invaluable for the assignment.",10.1002/anie.201206670,2012-10-18,0.5796305113924362
Journal of Organic Chemistry,Enantioselective Total Synthesis of (−)-Acutumine,"An account of the total synthesis of the tetracyclic alkaloid (-)-acutumine is presented. A first-generation approach to the spirocyclic subunit was unsuccessful as a result of incorrect regioselectivity in a radical cyclization. However, this work spawned a second-generation strategy in which the spirocycle was fashioned via a radical-polar crossover reaction. This process merged an intramolecular radical conjugate addition with an enolate hydroxylation and created two stereocenters with excellent diastereoselectivity. The reaction was promoted by irradiation with a sunlamp, and a ditin reagent was required for aryl radical formation. These facts suggest that the substrate may function as a sensitizer, thereby facilitating homolytic cleavage of the ditin reagent. The propellane motif of the target was then installed via annulation of a pyrrolidine ring onto the spirocycle. The sequence of reactions used included a phenolic oxidation, an asymmetric ketone allylation mediated by Nakamura's chiral allylzinc reagent, an anionic oxy-Cope rearrangement, a one-pot ozonolysis-reductive amination, and a Lewis acid promoted cyclization of an amine onto an alpha,beta-unsaturated dimethyl ketal. Further studies of the asymmetric ketone allylation demonstrated the ability of the Nakamura reagent to function well in a mismatched situation. A TiCl(4)-catalyzed regioselective methyl enol etherification of a 1,3-diketone completed the synthesis.",10.1021/jo902006q,2009-11-11,0.579630128058475
Organic Process Research & Development,Two Efficient Methods for the Preparation of 2-Chloro-6-methylbenzoic Acid,"Two efficient methods for the preparation of 2-chloro-6-methylbenzoic acid were developed: one based on nucleophilic aromatic substitution and the other based on carbonylation. In the first approach, 2-chloro-6-fluorobenzaldehyde was converted to its n -butylimine, then treated with 2 equiv of methylmagnesium chloride in THF to give, after hydrolysis, 2-chloro-6-methylbenzaldehyde. Subsequent oxidation of this compound gave the title compound in 85% overall yield. In the second approach, 3-chloro-2-iodotoluene was efficiently carbonylated in methanol to give methyl 2-chloro-6-methylbenzoate, which after hydrolysis afforded the title compound in 94% yield (84% yield after recrystallization). The carbomethoxylation proceeded smoothly even at a high substrate-to-Pd ratio of 10 000. Both methods do not require isolation of intermediates and are suitable for the preparation of kilogram quantities of 2-chloro-6-methylbenzoic acid.",10.1021/op0102363,2002-02-22,0.5796256596046606
Journal of the American Chemical Society,Asymmetric Total Synthesis of Clionastatins A and B,"Herein we report the first total synthesis of polychlorinated steroids clionastatins A and B, which was accomplished asymmetrically by means of a convergent, radical fragment coupling approach. Key features of the synthesis include an Ireland-Claisen rearrangement to introduce the C5 stereocenter (which was ultimately transferred to the C10 quaternary stereocenter of the clionastatins via a traceless stereochemical relay), a regioselective acyl radical conjugate addition to join the two fragments, an intramolecular Heck reaction to install the C10 quaternary stereocenter, and a diastereoselective olefin dichlorination to establish the synthetically challenging pseudoequatorial dichlorides. This work also enabled us to determine that the true structures of clionastatins A and B are in fact C14 epimers of the originally proposed structures.",10.1021/jacs.1c07511,2021-08-16,0.5796248684224578
Synthesis,A New Route to Benzo[<i>c</i>]thiophene and Related Compounds via Sulfilimines,,10.1055/s-1974-23290,1974-01-01,0.5796216136752071
Angewandte Chemie International Edition,Concise and Efficient Total Syntheses of Alkannin and Shikonin,"Two enantiomic natural products with wound-healing properties, alkannin (1) and shikonin (2), are accessible by a short and efficient total synthesis. The success was achieved by a novel protecting system for masking of 5,8-dihydroxy-1,4-naphthoquinones (naphthazarins) and a highly stereoselective ketone reduction.",10.1002/(sici)1521-3773(19980403)37:6<839::aid-anie839>3.0.co;2-j,1998-04-03,0.5796134876301766
Tetrahedron,"Oxidation of α-ylido, β-keto amides to vicinal tricarbonyls. Synthesis of a diketopiperazine precursor of bicyclomycin.","The Yoshimura intermediate in the total synthesis of bicyclomycin was prepared by intramolecular addition of an amide to an α,β-diketoamide. The resulting unsymmetrical diketopiperazine was then converted to the diol-ether target.",10.1016/s0040-4039(00)79110-6,1992-09-01,0.5796081200453939
Organic Process Research & Development,"Practical and Scalable Synthesis of 5,6-Dichlorofurazano[3,4-<i>b</i>]pyrazine","4 H,8 H -Difurazano[3,4- b:3′,4′- e ]pyrazine (DFP) is an important heat-resistant explosive intermediate, but its current synthesis process is still not scalable due to the low yields and acidic smokes in an internal chlorination step to give the intermediate DHFP. In this work, a DMA-promoted chlorination method to synthesize 5,6-dichlorofurazano[3,4- b ]pyrazine is described to solve the bottleneck of DFP synthesis. The best reaction conditions were confirmed to be DMA, DHFP, and POCl 3 (2:1:40) at 120 °C for 3 h, with an increased yield of 62%. This new method not only increases the yield but also eliminates the acid smokes during postprocessing, and it is likely to find practical applications in the synthesis of DFP and other heat-resistant explosives.",10.1021/acs.oprd.3c00196,2023-08-17,0.579606793360607
Journal of the American Chemical Society,Enantioselective Total Syntheses of Various Amphilectane and Serrulatane Diterpenoids via Cope Rearrangements,"Ampilectane and serrulatane natural products are structurally and stereochemically complex compounds that display various potent pharmacological activities ranging from anti-inflammatory to antituberculosis. A general synthetic route toward this family of natural products has been developed, which accomplished a number of amphilectane and serrulatane natural products. The key step employed a stereoselective Cope rearrangement either promoted by gold catalysis or thermal conditions, while a regioselective gold-catalyzed 6-endo-dig cyclization was optimized to afford a precursor. The preparation of the chiral β-ketoester as a starting material was established via an optimized asymmetric 1,4-addition followed by trapping with Mander's reagent, and this initially installed stereogenic center provided good control in the subsequent introduction of all the other stereocenters. A rarely investigated one-pot conversion of α-pyrone into phenol was also examined to enable the syntheses. DFT calculations explain the high stereoselectivity of the Cope rearrangement of the intermediate that eventually led to amphilectolide and caribenol A.",10.1021/jacs.6b02624,2016-04-26,0.579602630344329
Journal of the American Chemical Society,"Design and Implementation of an Efficient Synthetic Approach to Pyranosylated Indolocarbazoles:  Total Synthesis of (+)-RK286c, (+)-MLR-52, (+)-Staurosporine, and (−)-TAN-1030a","A total synthesis of the natural products (+)-staurosporine ( 2 ), (+)-RK286c ( 3 ), (−)-TAN-1030a ( 4 ), and (+)-MLR-52 ( 5 ) has been achieved. The synthetic strategy involves the stereoselective ring expansion of a furanosylated indolocarbazole [(+)- 8 ] to a pyranosylated congener [(+)- 12 ] that serves as a common intermediate in the production of 2 − 5 .",10.1021/ja971304x,1997-10-01,0.5796003945320451
Journal of Organic Chemistry,Chemical Synthesis of the Pentasaccharide Related to the Exopolysaccharide of <i>Aeromonas veronii</i> bv. Sobria Strain K49,Total synthesis of the pentasaccharide repeating unit of the exopolysaccharide of Aeromonas veronii bv. sobria strain K49 has been accomplished through a convergent [3 + 2] block synthesis strategy. Rationally designed derivatives of the challenging D-fucosamine and 3-acetamido D-quinovose units have been synthesized through protecting group manipulations and inserted into the target oligosaccharide through stereoselective glycosylations. The number of synthetic intermediates gave nice crystals that helped determine their chemical structures unambiguously.,10.1021/acs.joc.5c01883,2025-10-13,0.5795988777795851
Tetrahedron,Asymmetric synthesis of the core structure of the Melodinus alkaloids,,10.1016/s0040-4039(98)02510-6,1999-01-01,0.5795988612945556
Tetrahedron,A formal synthesis to (+)-nephrosteranic acid from chiral nitroalkyl derivatives,,10.1016/j.tetlet.2009.08.087,2009-08-30,0.5795987063201417
Synlett,Synthesis of (±)-Smenochromene D (Likonide B) Using a Regioselective Claisen Rearrangement,"A synthesis of the unusual ansa farnesyl hydroquinone smenochromene D (likonide B) is described, in which the key steps are a regioselective microwave-mediated Claisen rearrangement of an aryl propargyl ether to deliver the chromene ring, and macrocyclisation via an intramolecular Mitsunobu reaction.",10.1055/s-2008-1032090,2008-02-12,0.579596740842587
Angewandte Chemie International Edition,Total Synthesis of Tetrodotoxin,"A total synthesis of tetrodotoxin was accomplished. A Diels-Alder reaction between a known enone and a siloxy diene gave a tricyclic product, the steric bias of which was used to construct the remaining stereogenic centers. A nitrogen atom was introduced either by a four-step sequence involving a Curtius rearrangement, or a three-step sequence featuring a newly developed transformation of a terminal alkyne into a nitrile. Introduction of the guanidine moiety followed by the formation of the heterocyclic system by cascade reactions led to tetrodotoxin.",10.1002/anie.201916611,2020-01-27,0.5795959580266653
Organic Letters,Total Synthesis of the Marine Natural Product (−)-Clavosolide A. A Showcase for the Petasis−Ferrier Union/Rearrangement Tactic,"[Structure: see text] The total synthesis of the marine diolide (-)-clavosolide A has been achieved in 17 steps (longest linear sequence) from commercially available crotonaldehyde exploiting the Petasis-Ferrier union/rearrangement tactic to construct the requisite aglycon monomer. A one-pot esterification/lactonization employing the Yamaguchi protocol, followed by bis-glycosidation, furnished (-)-clavosolide A.",10.1021/ol0611752,2006-06-28,0.5795866316285513
Tetrahedron,Efficient synthesis of 5-aryl-2-vinylfurans by palladium catalyzed cross-coupling strategies,,10.1016/s0040-4039(99)00817-5,1999-06-01,0.5795860433644253
European Journal of Organic Chemistry,Total Synthesis of (+)‐Seimatopolide A,"Abstract The first enantioselective total synthesis of a polyhydroxylated macrolide, (+)‐seimatopolide A, was achieved. The key reactions, Sharpless asymmetric dihydroxylation, Yamaguchi esterification, and ring‐closing metathesis, provided easy access to the target molecule from L ‐aspartic acid. Further, the absolute stereochemistry of the natural product has also been revised.",10.1002/ejoc.201200732,2012-08-08,0.5795851576169432
Tetrahedron,"An asymmetric synthesis of cis, anti, cis-tricyclo[5,3,0,02,6]decanes applying γ-hydroxymethyl-γ-butyrolactone as a chiral synthon. First asymmetric total synthesis of (−)-β-bourbonene",,10.1016/s0040-4039(00)87626-1,1982-01-01,0.5795849423807651
Synlett,"The First Asymmetric Synthesis of (1<i>R</i>,1′<i>S</i>)-1-[1′-(Benzyloxycarbonyl-methylamino)-2′-phenylethyl]oxirane: a Promising Building Block for the Synthesis of Peptide Mimics",All articles of this category The threo N-methyl oxirane 5 was prepared from ( S )- N -methyl phenylalanine by bromoketone reduction or by epoxidation routes. The unexpected stereochemical result of the reduction of bromoketone 7 leading to the threo isomer is discussed. amino epoxides - N-methyl amino acid - diastereoselective bromoketone reduction,10.1055/s-1998-1558,1998-01-01,0.5795828845521331
Journal of Organic Chemistry,Enantioselective [4 + 2] Cycloadditions of <i>o</i>-Quinone Methides:  Total Synthesis of (+)-Mimosifoliol and Formal Synthesis of (+)-Tolterodine,"The first example of an enantioselective cycloaddition of an o-quinone methide (o-QM) with a chiral enol ether is described along with the total synthesis of (+)-mimosifoliol and the formal synthesis of (+)-tolterodine. These syntheses exemplify a three-component, one-pot benzopyran approach for the construction of chiral benzylic junctions. Cycloadditions of various enol ethers and o-QMs are examined, and diastereoselectivities >95% are obtained with trans-2-phenyl-1-cyclohexanol and 2,2-diphenylcyclopentanol vinyl ethers.",10.1021/jo048703c,2004-12-01,0.5795824664636104
Organic Letters,Synthesis of an Orange Anthrathiophene Pigment Isolated from a Japanese Bryozoan,"A short, regiospecific synthesis of the naturally occurring anthrathiophene 1 from naphthazarin (7) is described.",10.1021/ol006127a,2000-06-22,0.5795790074296591
Journal of Organic Chemistry,Sulfamate-Tethered Aza-Wacker Strategy for a Kasugamine Synthon,"We present our preparation of a kasugamine synthon, which proceeds in 14 steps from a literature epoxide. We expect that this kasugamine derivative can be used for the total syntheses of kasugamycin, minosaminomycin, and analogue antibiotics. A key step in the synthesis is our laboratory's sulfamate-tethered aza-Wacker cyclization.",10.1021/acs.joc.3c02292,2023-12-08,0.5795772060322922
Journal of Organic Chemistry,Asymmetric Oxidative Cyclization of <i>o</i>-Phenolic Oxime-Esters:  First Synthesis of Enantiomerically Enriched Spiroisoxazoline Methyl Esters,"A new method for the synthesis of enantiomerically enriched cyclohexadienone spiroisoxazoline (-)-2a has been described. Asymmetric intramolecular oxidative cyclization of the o-phenolic oxime-ester 1c using a novel optically active tertiary alcohol (-)-3 as a chiral auxiliary proceeded smoothly to afford cyclohexadienone spiroisoxazoline 2c in 83% yield. Opitcally active tertiary alcohol (-)-3 was synthesizied from racemic (1S,8R,9R,10R)-8-phenyl-1-decalol (4) by optical resolution. Removal of the chiral auxiliary in 2c with CF(3)COOH followed by methylation gave methyl ester (-)-2a in 74% ee (71% chemical yield) having S-configuration. The absolute configuration of 2awas determined by the synthesis of the marine natural product (+)-aerothionin.",10.1021/jo970082i,1997-06-01,0.5795746847317257
Journal of Organic Chemistry,Synthesis and Biological Evaluation of the Southern Hemisphere of Spirastrellolide A and Analogues,"The synthesis and biological evaluation of truncated spirastrellolide A analogues comprised of the southern hemisphere against protein phosphatase 2A are described. A convergent synthesis was designed featuring two gold-catalyzed cyclization reactions, specifically, a dehydrative cyclization of monoallylic diols for the synthesis of the tetrahydropyran (A-ring) and a regioselective spiroketalization for the efficient generation of the [6,6]-spiroketal (B, C-ring system). The synthesis of the southern hemisphere of spirastrellolide A was achieved involving the longest linear sequence of 19 steps. A total of eight spirastrellolide A analogues were synthesized, and preliminary PP2A enzyme assay inhibition studies were performed for the first time on analogues of the southern hemisphere. Several analogues showed inhibition, which is a positive indication and perhaps suggests that the unsaturated spiroketal fragment might be crucial to induce PP2A inhibition.",10.1021/acs.joc.0c01867,2020-10-28,0.5795743124748434
Journal of Organic Chemistry,An Efficient Bidirectional Approach to the <i>C</i><sub>2</sub>-Symmetric Stereoisomers of the Bistetrahydrofuran Core of the Acetogenins,"A bidirectional route to nonracemic C(2)-symmetric bistetrahydrofuran units related to acetogenin natural products was developed starting from the (S,S)-tartrate-derived dialdehyde 3.3. Bis-homologation with the (R)-alpha-OMOM crotylstannane (R)-4.1 in the presence of InCl(3) afforded the anti adduct, diol 4.3. The derived tosylate 4.4, upon treatment with TBAF in THF, underwent sequential TBS cleavage and cyclization to the (R,R,R,R,R,R)-bis-OMOM bistetrahydrofuran 4.7. The epimeric (S,R,R,R,R,S)-bis-OMOM bistetrahydrofuran 4.10 was prepared along similar lines, except that the (R)-alpha-OMOM crotylstannane (R)-4.1 was first converted to the (R)-gamma-isomer (R)-4.2 with BF(3).OEt(2). Subsequent addition of dialdehyde 3.3 led to the diol adduct 4.5, which after tosylation and treatment with TBAF, yielded the bistetrahydrofuran 4.10. By repeating the aforementioned sequences, but starting with the (S)-alpha-OMOM-crotylstannane (S)-4.1, the (S,S,R,R,S,S)- and the (R,S,R,R,S,R)-bistetrahydrofurans 5.5 and 5.8 were prepared. A variation on the foregoing sequence in which the OTBS grouping of the adduct was converted to a mesylate and the OH group was used to effect intramolecular displacement was also examined. Accordingly, adduct ent-5.3 from BF(3)-promoted addition of stannane (R)-4.2 and ent-3.3, the enantiomer of aldehyde 3.3, was acetylated. Cleavage of the TBS ether followed by mesylate formation and then concommitant acetate hydrolysis and cyclization with methanolic Triton B yielded the bis-OMOM bistetrahydrofuran 5.5. An analogous sequence was used to convert adduct 4.3 to ent-4.10. In this case, acetate saponification was effected with methanolic K(2)CO(3), and the resulting diol, 7.4, was cyclized with NaH in THF.",10.1021/jo9603789,1996-01-01,0.5795690592705803
Journal of the American Chemical Society,"A Highly Stereoselective, Modular Route to (<i>E</i>)-Vinylsulfones and to (<i>Z</i>)- and (<i>E</i>)-Alkenes",A recently discovered radical fragmentation of 2-fluoro-6-pyridinoxy derivatives allows a new highly stereoselective and convergent route to (E)-vinylsulfones from allylic alcohols. Reductive desulfonylation or nickel-catalyzed couplings furnish di- and trisubstituted (E)- and (Z)-alkenes.,10.1021/ja207944c,2011-09-20,0.5795657096163775
Angewandte Chemie International Edition,Total Synthesis of (+)‐MPC1001B,"The first total synthesis of an epidithiodiketopiperazine alkaloid, (+)-MPC1001B, was accomplished. This synthesis features a tetra-n-butylammonium fluoride mediated intramolecular aldol reaction for forming the 15-membered macrolactone ring, and the construction of an epidithiodiketopiperazine substructure through a stepwise sulfenylation reaction involving a novel trityl trisulfide (TrSSS)-group transfer.",10.1002/anie.201507830,2015-10-23,0.57956419928106
Journal of the American Chemical Society,"Total Synthesis, Assignment of Absolute Stereochemistry, and Structural Revision of Chlorofusin","The first total synthesis of chlorofusin was accomplished in a convergent fashion. With all four unambiguous diastereomeric model chromophores as references, the absolute stereochemistry of the chlorofusin chromophore was determined and revised to be (4 S,8 R,9 S ) by 1 H NMR studies and asymmetric synthesis. This allows the complete structure of natural chlorofusin to be assigned for the first time. Enantioselective copper-mediated oxidation of 4, mild coupling of azaphilone 2 with the free amine-bearing cyclopeptide 3, and a one-pot three-step protocol for the final spiro-aminal formation were successfully achieved with high efficiency to yield the correct stereochemical product 1a .",10.1021/ja072225g,2007-05-01,0.5795636313615157
Organic Letters,Variable and Stereoselective Synthesis of Azasugar Analogues by a Ruthenium-Catalyzed Ring Rearrangement,A novel ruthenium-catalyzed ring opening/ring closing tandem metathesis reaction with a catalytic transfer of stereocenters from a ring to an olefinic chain is described. This ring rearrangement serves as the key step in the stereoselective synthesis of the new azasugar analogues 1 and 2.,10.1021/ol000188r,2000-11-11,0.5795615822986023
Synlett,Enantioselective Synthesis of the Hexahydrobenzofuran Part of Avermectins,"All articles of this category An asymmetric synthesis of the southern C 1 -C 9 bicyclic fragment of avermectins has been developed in 13 steps from a propargyl ether and 2-methylhept-2-en-6-one via an acyclic diester intermediate [dimethyl (2 R ,3 S )-3, 4-isopropylidenedioxy-4-methyl-2-propargyloxyheptanedioate]. A Sharpless catalytic epoxidation reaction and a stepwise Dieckmann reaction-radical cyclisation approach were used for the construction of the optically active hydrobenzofuran system.",10.1055/s-1990-21245,1990-01-01,0.5795605655235957
Synthesis,"A New Direct Synthesis of Derivatives of the <i>s</i>-Triazolo[1,5-<i>a</i>]pyridine Ring System",,10.1055/s-1982-30031,2002-05-15,0.5795484458178518
Synthesis,An Improved Synthesis of Trisubstituted Ethylenes (Olefins) via Organoboranes,,10.1055/s-1980-29285,1980-01-01,0.5795465987482232
Organic Letters,"An Efficient and General Enantioselective Synthesis of Sphingosine, Phythosphingosine, and 4-Substituted Derivatives","A general and efficient protocol for the enantioselective synthesis of sphingosine, phythosphingosine, and 4-substituted derivatives was established. These compounds were obtained from a common intermediate prepared from butadiene monoepoxide by a synthetic sequence involving enantioselective allylic substitution, cross-metathesis, and dihydroxylation.",10.1021/ol802379b,2008-12-02,0.5795460463715726
Organic Process Research & Development,Large-Scale Synthesis of the Anti-Cancer Marine Natural Product (+)-Discodermolide. Part 4:  Preparation of Fragment C<sub>7</sub><sub>-</sub><sub>24</sub>,"Coupling of C 9 - 14 ( 4 ) and C 15 - 21 ( 5a ) fragments to produce the cis -trisubstituted olefin was achieved using Suzuki-type coupling conditions employed by Marshall ( 5a / tert -BuLi/B-OMe-9-BBN added to 4 /Cs 2 CO 3 /Pd(dppf) 2 ). The terminal ( Z )-diene moiety was attached to aldehyde 10 by using a sequential Nozaki−Hiyama allylation and Peterson olefination sequence; careful monitoring of the disappearance of both diastereomeric β-hydroxysilanes was found to be essential for achieving a high yield. In the oxidation of alcohols 12 and 16 to 13 and 7, respectively, using iodobenzene diacetate and TEMPO, addition of a trace of water was found to be crucial for complete conversion. The C 8 - 9 ( Z )-olefin functionality was introduced on to aldehyde 13 using a Still−Gennari HWE reaction. Subsequent carbamate installation at C-19 followed by a reduction/oxidation sequence gave the title fragment C 7 - 24 ( 7 ) ready to be coupled with the C 1 - 6 fragment, which is described in Part 2 of this series.",10.1021/op034133r,2003-12-04,0.5795449358874909
Tetrahedron,Synthesis of a new conformationally constrained glycoamino acid building block,,10.1016/s0040-4039(03)01586-7,2003-08-01,0.5795400697555809
Angewandte Chemie International Edition,Stereoselective Total Synthesis of Eburnane‐Type Alkaloids Enabled by Conformation‐Directed Cyclization and Rearrangement,"Controlling the cis C20/C21 relative stereochemistry remains an unsolved issue in the synthesis of eburnane-type indole alkaloids. Provided herein is a simple solution to this problem by developing a unified and diastereoselective synthesis of four representative members of this class of natural products, namely, eburnamonine, larutensine, terengganensine B, and melokhanine E. The synthesis features the following key steps: a) an α-iminol rearrangement transforming the 3-hydroxyindolenine into spiroindolin-3-one, b) a highly diastereoselective conformation-directed cyclization leading to the melokhanine skeleton with the desired C20/C21 cis stereochemistry, and c) either an aza-pinacol or an unprecedented α-aminoketone rearrangement converting spiroindolinone back into the indole skeleton.",10.1002/anie.201813920,2019-01-02,0.5795326358848412
Journal of Organic Chemistry,"Total Syntheses of β-Carboline Alkaloids Manzamine C, Orthoscuticelline C, and Quassidine S","A regioselective olefin hydrofunctionalization reaction of pavettine ( 4 ) with various nucleophiles was developed and used as the key step in the total syntheses of β-carboline natural products manzamine C ( 3 ), orthoscuticelline C ( 5 ), and quassidine S ( 6 ). In the 6-step total synthesis of manzamine C ( 3 ), an efficient two-step procedure, comprising a Wittig olefination reaction and a Fukuyama–Mitsunobu reaction, was devised for the synthesis of the N -macrocycle with a Z -olefin.",10.1021/acs.joc.3c02750,2024-01-19,0.5795316274090394
Synlett,A Facile Synthesis of 3′-Fluoro Hexitol Adenosine and Guanosine Phosphoramidites,"Abstract We report a convenient and scalable synthetic approach for the synthesis of 3′-fluoro hexitol adenosine and guanosine nucleoside analogues and corresponding phosphoramidites in good yield. 1,5-Anhydro-4,6-O-benzylidene-d-glucitol was converted into 1,5-anhydro-4,6-O-benzylidene-3-deoxy-3-fluoro-2-O-trifluoromethanesulfonyl-d-altritol in a three-step process. Glycosylation using adenosine or 2-amino-6-iodopurine yielded the corresponding nucleoside analogues in excellent yield. Based on this strategy, a highly concise and scalable synthesis of 3′-fluoro hexitol purine nucleosides (1–2 g, 18–21% overall yield) was accomplished, which will enable the use of 3′-fluoro hexitol nucleic acids for genetic medicine development and diagnostic applications.",10.1055/s-0042-1751507,2023-10-19,0.5795300547978756
Journal of the American Chemical Society,Acquisition of a Potent and Selective TC-PTP Inhibitor via a Stepwise Fluorophore-Tagged Combinatorial Synthesis and Screening Strategy,"Protein tyrosine phosphatases (PTPs) regulate a broad range of cellular processes including proliferation, differentiation, migration, apoptosis, and immune responses. Dysfunction of PTP activity is associated with cancers, metabolic syndromes, and autoimmune disorders. Consequently, small molecule PTP inhibitors should serve not only as powerful tools to delineate the physiological roles of these enzymes in vivo but also as lead compounds for therapeutic development. We describe a novel stepwise fluorophore-tagged combinatorial library synthesis and competitive fluorescence polarization screening approach that transforms a weak and general PTP inhibitor into an extremely potent and selective TC-PTP inhibitor with highly efficacious cellular activity. The result serves as a proof-of-concept in PTP inhibitor development, as it demonstrates the feasibility of acquiring potent, yet highly selective, cell permeable PTP inhibitory agents. Given the general nature of the approach, this strategy should be applicable to other PTP targets.",10.1021/ja903733z,2009-08-19,0.5795261027581843
Synthesis,A New Simple Synthesis of 5-Aryl-4-methoxycarbonyl-3-methyl-2-cyclohexenones,,10.1055/s-1983-30238,1983-01-01,0.5795258141192754
Organic Process Research & Development,"Synthetic Story of a Blockbuster Drug: Reboxetine, a Potent Selective Norepinephrine Reuptake Inhibitor","α-Aryloxybenzyl analogues of morpholine are a significant class of compounds because of their influence on the central nervous system (CNS), with particular concentration on their antidepressant potency. (±)-Reboxetine, an example of such α-aryloxybenzyl analogues, is an orally active and selective noradrenaline reuptake inhibitor that is presently recognized as a prescription drug in over 60 countries for depressive sickness and has been spaciously studied for its pharmacological characteristics. (+)-( S, S )-Reboxetine is presently undergoing advanced clinical evaluation as a potential treatment for neuropathic and fibromyalgia pain. Scheming well-organized approaches to access reboxetine and its derivatives represents a significant endeavor not only for developing antidepressant drugs but also advancing medical studies by radiolabeling of reboxetine derivatives with 11 C, 18 F, or 123 I as potential positron emission tomography radioligands for imaging the brain norepinephrine transporter system. Therefore, to fulfill the challenge of creating the reboxetine architecture by improved synthetic routes, the review combines all of the literature synthetic processes for reboxetine and its derivatives on one platform. Cons and pros of each synthetic method are discussed in this review, which will be very fruitful for the synthetic and medical communities to increase the diversity of synthetic procedures and to develop new concepts and perceptions.",10.1021/acs.oprd.7b00265,2017-10-02,0.5795253897453456
Tetrahedron,One-step conversion of flavanones into isoflavones: a new facile biomimetic synthesis of isoflavones,,10.1016/s0040-4039(00)88565-2,1990-01-01,0.5795159776419653
Synlett,Asymmetric Total Synthesis of (2E)-Macrolactin 3,"Abstract Asymmetric total synthesis of (2E)-macrolactin 3 has been accomplished in a highly convergent manner utilizing our earlier developed tandem isomerization followed by C–O and C–C bond-forming reaction, Sharpless asymmetric dihydroxylation, and a late-stage intramolecular Heck coupling reaction. Comparison of the NMR spectra of the coupled product and thorough analysis of the 2D NMR data of the final compound led to the conclusion that the Z-double bond at C2 was isomerized during the coupling reaction.",10.1055/a-1957-3966,2022-10-07,0.5795099043582541
Synthesis,An Efficient Route for the Synthesis of Isochromenocarbazolones through Palladium-Catalyzed Intramolecular ortho-Arylation,"A new efficient protocol for the synthesis of iso­chro­meno[3,4-b]-, [4,3-a]-, -[4,3-b]-, and -[3,4-c]carbazolones has been successfully established via palladium-catalyzed intramolecular ortho-arylation of C-H bond under ligand-free conditions.",10.1055/s-0030-1260162,2011-08-08,0.5795090075780466
Tetrahedron,A new synthesis of pyridinyl trifluoromethanesulfonates via one-pot diazotization of aminopyridines in the presence of trifluoromethanesulfonic acid,,10.1016/j.tetlet.2014.05.052,2014-05-21,0.5795026405508128
Tetrahedron,"A new strategy for the synthesis of 4,6-di-tert-butyl-2,2-dipentyl-2,3-dihydro-5-benzofuranol (BO-653), a potent antiatherogenic antioxidant",,10.1016/j.tetlet.2010.07.035,2010-07-20,0.5794967962941822
Tetrahedron,"Asymmetric synthesis with amino acid II asymmetric synthesis of optically active 4,4-disubstituted-cyclohexenone",,10.1016/s0040-4039(01)88663-9,1969-01-01,0.5794925984909277
Tetrahedron,NMR proofs of the involvement of an allenyl-naphthol as a key-intermediate in the photochromic process of [3H]-naphthopyrans,,10.1016/s0040-4039(02)02513-3,2003-01-01,0.5794906521901405
Journal of Organic Chemistry,Novel Approach to 5-Substituted Proline Derivatives Using a Silver-Catalyzed Cyclization as the Key Step,"A novel synthetic approach to the synthesis of enantiomerically pure 2,5-disubstituted pyrrolines is described. The methodology involves a Ag-catalyzed 5-endo-dig cyclization of enantiopure aryl-substituted acetylene-containing amino acids. It has also been shown that the obtained pyrrolines can be efficiently transformed into the corresponding saturated 5-aryl-substituted proline derivatives.",10.1021/jo0484023,2005-01-26,0.5794897735366864
Tetrahedron,"Emeniveol; A new pollen growth inhibitor from the fungus, Emericella nivea",,10.1016/s0040-4039(00)60913-9,1992-11-01,0.5794859311452435
Tetrahedron,Novel stereoselective total synthesis of 14α-hydroxyestrone methyl ether,,10.1016/s0040-4039(01)85871-8,1979-01-01,0.5794822894441894
Organic Letters,Synthesis of 5′-Methylene-Phosphonate Furanonucleoside Prodrugs: Application to <scp>D</scp>-2′-Deoxy-2′-α-fluoro-2′-β-<i>C</i>-methyl Nucleosides,A new and facile synthetic pathway to metabolically stable 5'-methylene-bis(pivaloyloxymethyl)(POM)phosphonate furanonucleoside prodrugs is reported. The key step involves a Horner-Wadsworth-Emmons reaction of a tetra(pivaloyloxymethyl) bisphosphonate salt with appropriately protected 5'-aldehydic nucleosides. This efficient approach was applied for the synthesis HCV related 2'-deoxy-2'-α-fluoro-2'-β-C-methyl nucleosides.,10.1021/ol301937v,2012-08-23,0.5794776278215067
Tetrahedron,"Efficient synthesis of 2,6-dioxo-1,2,3,4,5,6-hexahydroindoles based on the synthesis and reactions of (2,4-dioxocyclohex-1-yl)acetic acid derivatives",,10.1016/j.tetlet.2008.02.027,2008-02-12,0.5794758348843153
Journal of Organic Chemistry,Synthesis of Isoindolobenzazepine Alkaloids Based on Radical Reactions or Pd(0)-Catalyzed Reactions,Methods for synthesis of a ring system characteristic of isoindolobenzazepine alkaloids were studied. Synthesis of lennoxamine and a formal synthesis of chelenine were accomplished in a short route via radical or Pd(0)-catalyzed cyclization as the key step. An altenative approach based on a radical migration of a cyano group or Pd(0)-catalyzed carbonylation was also developed for both alkaloids.,10.1021/jo900311g,2009-05-21,0.5794718688278208
Tetrahedron,Organozirconocene-mediated polyene synthesis: Preparation of asukamycin and manumycin a side chains,,10.1016/s0040-4039(97)01129-5,1997-07-01,0.579471424433818
Angewandte Chemie International Edition,Oxalyl Boronates Enable Modular Synthesis of Bioactive Imidazoles,"Described herein is the preparation of oxalyl boronate building blocks and their application for the construction of heterocycles. The oxalyl unit, readily accessible through commercially available starting materials, enables a modular approach for the synthesis of imidazoles. A variety of aromatic, heteroaromatic, and alkyl carboxaldehydes were condensed with oxalyl boronates to afford substituted boryl imidazoles in a regiocontrolled fashion. Subsequent palladium-catalyzed cross-coupling with haloarenes furnished the desired trisubstituted imidazole scaffolds. To demonstrate the utility of these scaffolds, potent inhibitors of the serine/threonine-protein kinase STK10 were synthesized.",10.1002/anie.201611006,2017-03-07,0.5794713153317718
Organic Letters,"Regio- and Enantioselective Synthesis of 1,2-Diamine Derivatives by Copper-Catalyzed Hydroamination","A highly regio- and enantioselective synthesis of 1,2-diamine derivatives from γ-substituted allylic pivalamides using copper-catalyzed hydroamination is reported. The N-pivaloyl group is essential, in both facilitating the hydrocupration step and suppressing an unproductive β-elimination from the alkylcopper intermediate. This approach enables an efficient construction of chiral differentially protected vicinal diamines under mild conditions with broad functional group tolerance.",10.1021/acs.orglett.9b01592,2019-05-17,0.5794669918131646
Tetrahedron,Synthesis of an advanced intermediate enroute to (−)-clavosolide A,,10.1016/j.tetlet.2017.05.033,2017-05-13,0.5794555940838995
Tetrahedron,Valorization of Madagascar’s CNSL via the synthesis of one advanced intermediate (3-Pentadecylcyclohexanone),,10.1016/j.tetlet.2017.04.093,2017-05-02,0.5794555940838995
Synthesis,Straightforward Synthesis of Depsiphosphonopeptides via Mannich-Type Multicomponent Condensation,"A straightforward method for the synthesis of depsiphosphonopeptides via a Mannich-type multicomponent condensation of simple starting materials, such as benzyl carbamate, aldehydes, and 1-carbethoxyalkyl phosphorodichloridites, was developed. Compared to previous methods, our strategy provides a more efficient, convenient, and practical route for the preparation of depsiphosphonopeptides under mild reaction conditions with good yields. Such a strategy avoids the initial synthesis of 1-aminoalkyl­phosphonic acid or 1-aminoalkylphosphonous acid derivatives as starting materials.",10.1055/s-2006-926324,2006-01-01,0.5794541669643484
Angewandte Chemie International Edition,Stereochemical Assignment of the Protein–Protein Interaction Inhibitor JBIR‐22 by Total Synthesis,"Recent reports have highlighted the biological activity associated with a subfamily of the tetramic acid class of natural products. Despite the fact that members of this subfamily act as protein-protein interaction inhibitors that are of relevance to proteasome assembly, no synthetic work has been reported. This may be due to the fact that this subfamily contains an unnatural 4,4-disubstitued glutamic acid, the synthesis of which provides a key challenge. A highly stereoselective route to a masked form of this unnatural amino acid now enabled the synthesis of two of the possible diastereomers of JBIR-22 and allowed the assignment of its relative and absolute stereochemistry.",10.1002/anie.201411141,2015-02-04,0.5794539828846679
European Journal of Organic Chemistry,"A Chiral β,δ-Dioxo-ε-sulfinyl Ester in a Convergent Enantioselective Synthesis towards the C1–C13 Polyol Fragment of Amphotericin B",,10.1002/(sici)1099-0690(199911)1999:11<3021::aid-ejoc3021>3.3.co;2-i,1999-11-01,0.5794515114263544
Organic Letters,"One-Pot Stereoselective Synthesis of 2,3-Diglycosylindoles and Tryptophan-C-glycosides via Palladium-Catalyzed C–H Glycosylation of Indole and Tryptophan","We described a novel palladium-catalyzed C-H glycosylation of indole or tryptophan for a one-pot stereoselective synthesis of 2,3-diglycosylindoles and tryptophan-C-glycosides. In this strategy, the use of air and base-free and ligand-free conditions provided a highly efficient route to construct C-glycosides. The method can be applied to a wide range of cost-effective and convenient glycosyl chloride donors. Mechanistic studies indicated that the indole 2,3-diglycosylation sequence was C3 and then C2.",10.1021/acs.orglett.2c00602,2022-03-23,0.5794476307247282
Synthesis,Convenient Syntheses of Tetraarylmethane Starting Materials,"Tetraphenylmethane (1) and several functionalized tetraphenylmethanes 4-7, all of them useful building blocks for the construction of tetraarylmethane frameworks, are readily synthesized by improved standard procedures in multigram quantities. The structure of compound 5 has been additionally corroborated by an X-ray structure analysis. The novel class of tetrakis(thiazolylphenyl)methanes 8 showing a significant blue emission upon UV-excitation can be prepared in good yield by Hantzsch synthesis starting from the tetra(α-bromoketone) derivative 4b.",10.1055/s-2002-32526,2002-06-28,0.5794464087841127
Angewandte Chemie International Edition,Rhodium‐Catalyzed Highly Regio‐ and Enantioselective Hydrogenation of Tetrasubstituted Allenyl Sulfones: An Efficient Access to Chiral Allylic Sulfones,"A highly regio- and enantioselective hydrogenation of challenging tetrasubstituted allenyl sulfones has been developed, affording chiral allylic sulfones in good yields with excellent regio- and enantioselectivities (up to 99 % yield and 99 % ee). This method provides an efficient and concise route to chiral allylic sulfones, thus offering an atom-economic process with a wide range of potential applications in organic synthesis and medicinal chemistry.",10.1002/anie.201804891,2018-08-20,0.5794463341701427
Organic Letters,Direct Oxidative Cleavage of Multiple C<sub>sp<sup>3</sup></sub>–H Bonds and a C–C Bond in 2-(Pyridin-2-yl)acetate Derivatives: Formal [3 + 1 + 1] Synthesis of 3-(Pyridin-2-yl)indolizine Skeletons,"A novel iodine-promoted oxidative cross-coupling/cyclization of 2-(pyridin-2-yl)acetate derivatives and methyl ketones via the cleavage of multiple C sp 3 –H bonds has been developed, which also achieved efficient cleavage of a C–C bond in the 2-(pyridin-2-yl)acetate derivatives. This protocol represents an elegant molecular fragment assembly of diverse 3-(pyridin-2-yl)indolizines via a formal [3 + 1 + 1] annulation. Notably, the pyridine derivatives serve two pivotal roles to provide two fragments to construct 3-(pyridin-2-yl)indolizine skeletons, rather than the single role in building common indolizines.",10.1021/acs.orglett.7b01492,2017-06-07,0.5794457801758197
European Journal of Organic Chemistry,Synthesis of Euchrestifoline Using Iron‐ and Palladium‐Catalyzed C–H Bond Activations,"We describe a short and efficient synthetic route to euchrestifoline. Key steps of our approach are the iron(III)‐catalyzed Wacker‐type oxidation of a chromene derivative with hexadecafluorophthalocyanine‐iron (FePcF 16 ) as catalyst, a palladium(0)‐catalyzed Buchwald–Hartwig amination, and the final palladium(II)‐catalyzed oxidative cyclization of the resulting diarylamine to the natural product.",10.1002/ejoc.201800872,2018-06-07,0.5794405427829729
Organic Letters,Asymmetric Alcohol C–H Allylation and <i>syn</i>-Crotylation: C9–C20 of Tetrafibricin,The C9-C20 segment of the fibrinogen receptor inhibitor tetrafibricin was prepared in 10 steps (longest linear sequence). Ruthenium catalyzed enantioselective syn-crotylation is used to construct C9-C13. Iridium catalyzed asymmetric alcohol C-H allylation of a commercial malic acid derived alcohol is used to construct C14-C20. Recovery and recycling of the iridium catalyst is described.,10.1021/ol403566w,2014-01-14,0.5794400956294442
Organic Process Research & Development,Development of an Enantioselective Hydrogenation Based Synthesis of a Glucokinase Activator,"This article describes the development and optimization of chemical reactions and subsequent multikilogram preparation of the glucokinase activator ( R )- 1 to fund clinical evaluation as a potential therapeutic for type II diabetes. The major process developments presented here are a Wittig olefination isomerization based synthesis of an E -acrylic acid, an optimized enantioselective hydrogenation of the E -acrylic acid, and a challenging final amide coupling.",10.1021/op300053a,2012-04-12,0.5794292119851381
Synthesis,An Improved Synthesis of Fluorinated Imidoylsilanes,"A practical and efficient method for the preparation of fluorinated imidoylsilanes is described. The key step involves finely controlled activation of C-Cl and C-Br bonds in fluorinated imidoyl chlorides and bromides, respectively.",10.1055/s-2006-942361,2006-05-23,0.5794158748587693
Tetrahedron,Concise synthesis of the bicyclic core of the chromoprotein antibiotics kedarcidin and neocarzinostatin by transannular reductive cyclization of a tetrayne precursor,,10.1016/s0040-4039(98)02279-5,1998-12-01,0.579414597059984
Tetrahedron,"Novel highly potent, structurally simple γ-trifluoromethyl γ-sulfone hydroxamate inhibitor of stromelysin-1 (MMP-3)",,10.1016/j.tetlet.2005.02.063,2005-03-03,0.579412106628133
Synlett,Stereoselective Total Synthesis of (-)-9-Deoxygoniopypyrone,Stereoselective synthesis of (-)-9-deoxygoniopypyrone was achieved from the naturally occurring L-(+)-tartaric acid. Key step involves the elaboration of a \\gamma -hydroxybutyramide to the title compound involving high-yielding stereoselective transformations.,10.1055/s-2007-973873,2007-04-01,0.579405327936836
Tetrahedron,A new synthesis of β-lactams from lithium ester enolates andenolizable aldimines,,10.1016/s0040-4039(00)95517-5,1987-01-01,0.5794021427355602
Synthesis,A General Approach to the Synthesis of Bisindolylmaleimides: Synthesis of Staurosporine Aglycone,"All articles of this category Bisindolylmaleimides are prepared in 65-95% yield by reaction of an indole Grignard with either 2,3-dichloro- N -methylmaleimide or 2,3-dichloromaleimide. A one-step synthesis of arcyriarubin A in 72% yield affords ready access to the staurosporine aglycone. dihalomaleimides - indolyl-MgBr - bisindolylmaleimides - arcyriarubin A - staurosporine aglycone",10.1055/s-1995-4146,1995-12-01,0.5794000795362498
Tetrahedron,A shorter route to () estrone,,10.1016/0040-4039(88)85065-2,1988-01-01,0.5793949627563352
Journal of Organic Chemistry,Flexible Synthesis of Metacycloprodigiosin and Functional Derivatives Thereof,"A conceptually new approach to m-pyrrolophane derivatives is outlined providing ready access to compound 23 which can be elaborated into the immunosuppressive alkaloid metacycloprodigiosin 2 according to literature procedures. The key steps of this sequence involve a palladium-catalyzed macrocyclization reaction of vinyl epoxide 10, the conversion of the alpha-pyrone derivative 14 into the pyrrole targets, and the attachment of the side chain via a Wittig (or Peterson) olefination followed by hydrogenation of the alkene formed over Crabtree's catalyst. The flexibility of this route is demonstrated by the synthesis of several analogues of the parent compound 23 which may help to assess the structure/activity profile of the prodigiosin family of natural products in more detail. The unusual pyrone structure 14 used to encode the meta-bridged pyrrolophane units was characterized by X-ray crystallography.",10.1021/jo991022a,1999-10-01,0.5793947590641155
Journal of the American Chemical Society,"Modular, Scalable Synthesis of Group A Streptogramin Antibiotics","Streptogramin antibiotics are used clinically to treat multidrug-resistant bacterial infections, but their poor physicochemical properties and narrow spectra of activity have limited their utility. New methods to chemically modify streptogramins would enable structural optimization to overcome these limitations as well as to combat growing resistance to the class. Here we report a modular, scalable synthesis of group A streptogramin antibiotics that proceeds in 6-8 linear steps from simple chemical building blocks. We have applied our route to the synthesis of four natural products in this class including two that have never before been accessed by fully synthetic routes. We anticipate that this work will lead to the discovery of new streptogramin antibiotics that overcome previous limitations of the class.",10.1021/jacs.7b08577,2017-09-13,0.5793929387911125
Organic Letters,Deconstruction−Reconstruction Strategy for Accessing Valuable Polyketides. Preparation of the C15−C24 Stereopentad of Discodermolide,"An advanced, known intermediate for discodermolide synthesis was prepared by an efficient sequence from the readily available fermentation product oleandomycin. The scheme makes use of a new method for the direct cleavage of aminoglycosides, a critical double-bond isomerization, and a selective protection of two of three hydroxyl groups in a modified oleandolide. This synthesis illustrates a new strategy, ""deconstruction-reconstruction"", for accessing stereochemically complex polyketide building blocks.",10.1021/ol702144u,2007-10-09,0.5793820177646019
Organic Process Research & Development,Ir/SpiroPAP Catalyzed Asymmetric Hydrogenation of a Key Intermediate of Montelukast: Process Development and Potential Impurities Study,"An efficient and robust process for the asymmetric hydrogenation of a key intermediate of Montelukast using the highly efficient and selective chiral spiro catalyst Ir/SpiroPAP is reported. The developed process was conducted at mild reaction temperature (30 °C) under a hydrogen pressure of 20 atm with low catalyst loading (S/C = 30 000) and afforded the desired chiral alcohol intermediate in 99.5% ee. This process currently has been carried out at 30 kg scale. The process-related impurities (impurities I–V ) were also identified, synthesized, and characterized by LC-MS and NMR techniques.",10.1021/acs.oprd.5b00339,2015-12-14,0.5793780681224409
Journal of Organic Chemistry,"Ellagitannin Chemistry. First Total Synthesis of the 2,3- and 4,6-Coupled Ellagitannin Pedunculagin","The biomimetic synthesis of pedunculagin (1) was accomplished through the sequential diastereoselective formation of two biphenyl C-C bonds. The synthesis strategy employed is predicated on extensive conformational modeling and involves initial oxidative coupling of the galloyl moieties at the O(2) and O(3) positions of an appropriately protected glucose-derived core, followed by installation and oxidative coupling of galloyl esters at the O(4) and O(6) positions.",10.1021/jo952130+,1996-01-01,0.5793773951946452
Tetrahedron,A Pd(0)-catalyzed route to 13-methylidenefarnesyl diphosphate,,10.1016/s0040-4039(00)77157-7,1994-04-01,0.5793769949060956
Journal of Organic Chemistry,Synthesis and Reactions of 2-Chloro- and 2-Tosyloxy-2‘-deoxyinosine Derivatives,"Convenient syntheses of 2-chloro- and 2-tosyloxy-2'-deoxyinosine as their tert-butyldimethylsilyl ethers are described. Both compounds can be synthesized via a common route and rely on commercially available 2'-deoxyguanosine. The present method leading to the chloro nucleoside is operationally simpler compared to previously reported glycosylation techniques where isomeric products were obtained. Both electrophilic nucleosides can be used for the preparation of N-substituted 2'-deoxyguanosine analogues via displacement of the leaving groups, and a comparison of their reactivities shows the chloro analogue to be superior. Interestingly, a Pd catalyst-mediated, two-step, one-pot conversion of an allyl-protected chloro nucleoside intermediate to the final modified 2'-deoxyguanosine derivatives is also feasible. On the basis of these observations, initial assessments of Pd-catalyzed aryl amination as well as a C-C cross-coupling have also been performed with the chloro and tosyloxy nucleoside substrates. Results indicate a potentially high synthetic utility of 2-chloro-2'-deoxyinosine and in many instances this derivative can supplant the bromo and fluoro analogues that are more cumbersome to prepare or are not readily available.",10.1021/jo050847j,2005-08-04,0.5793743721307105
Tetrahedron,Prostaglandin chemistry VII A synthesis of new 8-phenylthio-11-deoxyprostaglandins,,10.1016/s0040-4039(00)92583-8,1976-11-01,0.5793724680820413
Organic Letters,"Difluorocarbene-Triggered Cyclization: Synthesis of (Hetero)arene-Fused 2,2-Difluoro-2,3-dihydrothiophenes","An efficient method for the synthesis of (hetero)arene-fused 2,2-difluoro-2,3-dihydrothiophene derivatives using readily available sodium chlorodifluoroacetate (ClCF 2 CO 2 Na) has been developed. This transformation is achieved through a combination of a thiolate with difluorocarbene, followed by intramolecular nucleophilic addition to a ketone, cyano, or ester functional group.",10.1021/acs.orglett.0c02688,2020-08-20,0.5793681153847965
Organic Letters,"Generation of All-Carbon Quaternary Stereocenters at the C-3 Carbon of Lactams via [3,3]-Sigmatropic Rearrangement and Revision of Absolute Configuration: Total Synthesis of (−)-Physostigmine","A diastereoselective (up to >99%) route to all carbon quaternary stereocenters at the C-3 position of cyclic lactams has been developed via Johnson-Claisen rearrangement of γ-hydroxy-α,β-unsaturated lactams. It has been observed that olefin geometry plays an important role in the development of the absolute stereochemistry of the product. Dependence of product configuration on the olefin geometry is explained by postulating probable transition states. The success of this method has been shown for multigram-scale synthesis of these substituted lactams from commercially available cheap starting materials. The synthetic usefulness of this method is also demonstrated by carrying out the total synthesis of (-)-physostigmine.",10.1021/acs.orglett.7b03537,2017-12-22,0.579359377080052
Synthesis,"A Short and Efficient Synthesis of 3-[2,2,2-Trifluoroethyl]hexahydro-2<i>H</i>-1,4-diazepin-2-one","A short, high yielding, five-step synthesis of the pharmaceutically interesting fluorinated heterocycle, 3-[2,2,2-trifluoroethyl]hexahydro-2H-1,4-diazepin-2-one, has been developed.",10.1055/s-2007-983876,2007-09-01,0.5793572361926449
European Journal of Organic Chemistry,"Asymmetric Synthesis of the Indolo[2,3‐α]quinolizine Alkaloid (+)‐Cuscutamine via a Diastereoselective Intramolecular Pictet‐Spengler Reaction","Abstract A concise total synthesis of Cuscutamine was achieved involving a diastereoselective intramolecular acyl iminium ion mediated Pictet‐Spengler reaction. This synthetic strategy provided a direct route to (11 S , 13 R )‐Cuscutamine ( 2 ) in only 3 steps with an overall yield of 56 % and an enantiomeric ratio of 88 %. The diastereoselectivity of the reaction is consistent with previous studies that proceed via more highly puckered transition states and the present results thus reveal the importance of the steric contributions to the observed diastereoselectivity.",10.1002/ejoc.202400708,2024-07-04,0.5793546426505274
Organic Letters,A Convenient Allenoate-Based Synthesis of 2-Quinolin-2-yl Malonates and β-Ketoesters,"N-Protected o-aminobenzaldehydes smoothly react with α,γ-dialkylallenoates under Brønsted basic conditions to yield 2,3-disubstituted quinolines. This three-step reaction cascade of Michael addition, aldol condensation, and 1,3-N → C rearrangement uses the complete protecting group as a building block in a highly efficient C,C-bond formation of a new all-carbon quaternary center. Carbamate protected substrates (N-Boc, N-Cbz, N-Alloc) thus give 2-quinolin-2-yl-malonates, while amide protected substrates (N-Ac, N-Bz) afford 2-quinolin-2-yl-β-ketoesters in high yields.",10.1021/ol502554e,2014-09-12,0.5793460974528334
Tetrahedron,"New route to pyrido[1,2-b]pyridazinium inner salts. Evidence of a 1,3-dipolar cycloaddition-ring expansion process",,10.1016/s0040-4039(98)02406-x,1999-01-01,0.5793440655974836
Tetrahedron,"An efficient solvent-tuning approach for the rapid synthesis of thiazolidinone derivatives and the selective synthesis of 2-amino-4H-1,3-thiazin-4-one and dimethyl 3,3′-thiodiacrylates",,10.1016/j.tetlet.2014.08.032,2014-08-13,0.5793366457507614
Journal of Organic Chemistry,"A Tandem Horner−Emmons Olefination−Conjugate Addition Approach to the Synthesis of 1,5-Disubstituted-6-azabicyclo[3.2.1]octanes Based on the AE Ring Structure of the Norditerpenoid Alkaloid Methyllycaconitine","A novel Horner-Emmons olefination conjugate addition reaction of N-acetylamides to form 1,5-disubstituted-6-azabicyclo[3.2.1]octanes with two bridgehead quarternary carbon centers is reported. This reaction is a key step in an approach to the synthesis of small ring analogues based on the AE ring structure of the Delphinium norditerpenoid, methyllycaconitine (MLA) (1). Initially, 3-(hydroxymethyl)cyclohex-2-en-1-one (10) was selected as the starting material to these structures, but its generation proved inefficient. In contrast, the synthesis of 3-[(phenylthio)methyl]cyclohex-2-en-1-one (6) and 3-(1,3-dithian-2-yl)cyclohex-2-en-1-one (11) proceeded in good yield. Subsequent hydrocyanation, ketalization, reduction, acetylation, deprotection of the acetal, and Horner-Emmons olefination-conjugate addition reaction to form 1-[(phenylthio)methyl]-5-[(ethoxycarbonyl)methyl]-6-acetamido-6-azabicyclo[3.2.1]octane (28), 1-(1,3-dithian-2-yl)-5-[(ethoxycarbonyl)methyl]-6-acetyl-6-azabicyclo[3.2.1]octane (29), respectively, are reported, as well as for readily available 3-methylcyclohex-2-en-1-one (12). Studies on the Pummerer rearrangement of 28 and subsequent desulfurization and reduction to form an hydroxymethyl-substituted azabicyclo[3.2.1.]octane (40) and then selective protection to form a protected hydroxyethyl N-ethyl (hydroxymethyl)azabicyclo[3.2.1]octane (3) are also described.",10.1021/jo9519672,1996-01-01,0.5793362515946737
Synthesis,A Novel Synthesis of Trifluoromethyl Enones and Enediones,,10.1055/s-1998-2077,1998-06-01,0.5793347506218197
European Journal of Organic Chemistry,"Monohydrochloride Assisted Synthesis of Functionalized Isoxazoles and Pyrazoles from Allenic Ketones: First Synthesis of (<i>Z</i>)‐2‐Methyl‐7H‐benzo[b]pyrazolo[5,1‐d][1,5]oxazocines","A facile hydrochloride promoted regioselective synthesis of isoxazoles and pyrazoles from 1,2‐allenic ketones is reported. The reaction has been scaled up to gram scale. A direct 8‐ endo dig ring annulations towards the first synthesis of ( Z )‐2‐methyl‐7H‐benzo[b]pyrazolo[5,1‐d][1,5]oxazocine has been developed.",10.1002/ejoc.201900008,2019-02-18,0.5793190119098032
Synlett,An Expeditious Synthesis of (±)-Mimosifoliol Utilizing a Cascade Involving an<i>o</i>-Quinone Methide Intermediate,"An efficient synthesis of (±)-mimosifoliol is reported. The key transformation involves a domino sequence leading to an o-quinone methide and its subsequent consumption in 1,4-conjugate addition with a vinyl Grignard reagent.",10.1055/s-2003-42059,2003-01-01,0.5793188148571667
Angewandte Chemie International Edition,Highly Regio‐ and Enantioselective Synthesis of N‐Substituted 2‐Pyridones: Iridium‐Catalyzed Intermolecular Asymmetric Allylic Amination,"The first iridium-catalyzed intermolecular asymmetric allylic amination reaction with 2-hydroxypyridines has been developed, thus providing a highly efficient synthesis of enantioenriched N-substituted 2-pyridone derivatives from readily available starting materials. This protocol features a good tolerance of functional groups in both the allylic carbonates and 2-hydroxypyridines, thereby delivering multifunctionalized heterocyclic products with up to 98% yield and 99% ee.",10.1002/anie.201409976,2014-12-12,0.5793182340391113
Tetrahedron,Synthetic studies toward marine toxic polyethers [5] the total synthesis of okadaic acid,,10.1016/s0040-4039(00)84149-0,1986-01-01,0.5793176654036304
Journal of the American Chemical Society,Total Synthesis of Isokidamycin,"The synthesis of isokidamycin, which represents the first total synthesis of a bis-C-aryl glycoside natural product in the pluramycin family, has been completed. The synthesis features the use of a silicon tether as a disposable regiocontrol element in an intramolecular Diels-Alder reaction between a substituted naphthyne and a glycosyl furan and a subsequent O→C-glycoside rearrangement.",10.1021/ja107926f,2010-10-19,0.5793166675799659
Tetrahedron,Synthesis of arylethynylated cyclohexa-m-phenylenes via sixfold Suzuki coupling,,10.1016/j.tetlet.2008.05.150,2008-06-06,0.5793146350797606
Tetrahedron,"Preparation and reactions of cis-5,10-methanoxymethano-1-methyl-Δ1,9-2-octalone as an intermediate in the total synthesis of clerodane type diterpenes",,10.1016/0040-4039(80)88085-3,1980-01-01,0.5793104682511033
Organic Letters,A New Synthesis of <i>p</i>-Hydroxy Phenylglycine and Some Analogues from <i>p</i>-Benzoquinone,"[reaction: see text] A new route to p-hydroxy phenylglycine and N-substituted analogues has been developed starting from p-benzoquinone. 1,2-Addition of methyl lithioacetate to p-benzoquinone and subsequent quenching of the oxygen anion with methyl chloroformate, followed by an elimination-addition reaction with an appropriate amine, resulted in the desired amino acid derivatives. A diastereoselectivity of 60% was achieved using 8-phenylmenthyl acetate as the chiral auxiliary.",10.1021/ol9913183,2000-02-01,0.5793075688289292
Organic Letters,"Total Synthesis of Waltherione A, a Quinolone Alkaloid Fused with Oxabicyclo[3.2.1]octane","Waltherione A ( 1 ), a unique quinolone alkaloid fused with oxabicyclo[3.2.1]octane, was isolated originally from Waltheria douradinha and recently by us from a methanol extract of Melochia umbellata along with the related 3,4-dimethoxyquinoline paliasanines A–E. Compound 1 showed selective cytotoxicity against A549 and MCF-7 cell lines. Its interesting structural and biological features prompted several attempts at total synthesis and clarification of the absolute configuration, although none were successful to date. Now, we have accomplished the first total synthesis of 1 starting from commercially available benzosuberone in 21 steps as well as elucidated its absolute configuration.",10.1021/acs.orglett.3c01837,2023-06-22,0.5793058110730549
Journal of the American Chemical Society,"Asymmetric Total Syntheses of (−)-Jorumycin, (−)-Renieramycin G, 3-<i>e</i><i>pi</i>-Jorumycin, and 3-<i>e</i><i>pi</i>-Renieramycin G","The total synthesis of (-)-jorumycin (1) and (-)-renieramycin G (2) has been accomplished in 25 and 23 steps, respectively, from 5-benzyloxy-2,4-dimethoxy-3-methyl-benzyl alcohol. The synthesis features a substrate-tunable stereoselective intramolecular Pictet-Spengler-type reaction for the construction of the key pentacyclic core of both targets, bearing either the natural configuration or the epimeric configuration at C-3. With access to a C-3 epi-pentacyclic framework, 3-epi-jorumycin (32) and 3-epi-renieramycin G (34) were also successfully synthesized. Furthermore, preliminary biological evaluation of 3-epi-jorumycin (32), in addition to relevant synthetic intermediates, revealed that significant cytotoxicity had been retained in these compounds. Therefore, these early studies constitute the basis for a new structure activity relationship (SAR) investigation for this class of antitumor antibiotics.",10.1021/ja0535918,2005-08-19,0.5793035724211066
Tetrahedron,Elaboration of 1-benzoyltetrahydroisoquinoline derivatives employing a Pictet–Spengler cyclization with α-chloro-α-phenylthioketones. Synthesis of O-methylvelucryptine,,10.1016/s0040-4039(01)01998-0,2001-12-01,0.5792956706858289
Chemical Science,Dual role of nitroarenes as electrophiles and arylamine surrogates in Buchwald–Hartwig-type coupling for C–N bond construction,"A reductive and denitrative amination of nitroarenes has been developed, allowing the highly selective synthesis of various di- and triarylamines. The protocol employed synthetically upstream nitroarenes as both the electrophiles and amine sources.",10.1039/d3sc06618e,2024-01-01,0.5792947169980056
Tetrahedron,A new process for the enantioselective synthesis of chiral α-aryloxy- and α-hydroxy acids,,10.1016/s0040-4039(00)92655-8,1992-06-01,0.5792917775789079
Organic Letters,Synthesis and Biological Evaluation of Bicyclo[1.1.1]pentane-Containing Aromatic Lipoxin A<sub>4</sub> Analogues,"High Resolution Image Download MS PowerPoint Slide Lipoxins are important drivers of inflammation resolution, suggesting a potential therapeutic benefit. Bicyclo[1.1.1]pentanes (BCPs) are potential isosteric replacements for arenes and/or alkyl groups within drug candidates. We carried out an asymmetric synthesis of four BCP-containing synthetic lipoxin A 4 mimetics (BCP-sLXms) in which the key steps were a Suzuki coupling, an asymmetric ketone reduction, and a triethylborane-initiated radical bicyclopentylation. These mimetics were screened for their impact on inflammatory responses, and one imidazolo-BCP-sLXm ( 6a ) was found to possess high anti-inflammatory activity.",10.1021/acs.orglett.2c02345,2022-08-08,0.5792910001847486
Organic Letters,"Regioselective Synthesis of a <i>C</i>-4′′ Carbamate,<i>C</i>-6′′ <i>n</i>-Pr Substituted Cyclitol Analogue of SL0101",An asymmetric synthesis of two analogues of SL0101 ( 1 ) has been achieved. The effort is aimed at the discovery of inhibitors of the p90 ribosomal S6 kinase (RSK) with improved bioavailability. The route relies upon the use of the Taylor catalyst to regioselectively install C -3″ acetyl or carbamate functionality. This study led to the identification of a third-generation analogue of SL0101 with a C -4″ n -Pr-carbamate and a C -3″ acetate with improved RSK inhibitory activity.,10.1021/acs.orglett.0c00042,2020-02-03,0.5792907490351086
Tetrahedron,"Enantioselective synthesis of β,β-dialkyl α-hydroxy γ-butyrolactones",,10.1016/s0040-4039(01)01979-7,2001-12-01,0.5792895645869408
Tetrahedron,Synthesis of a new carbohydrate mimetics: “carbopeptoid” containing a C-1 carboxylate and C-2 amino group,Readily access to a new class of carbohydrate mimetics has been demonstrated from a d-glucosamine derivative by the synthesis of a tetrameric carbopeptoid in which the glycosidic bonds are replaced with amido linkages.,10.1016/0040-4039(96)00094-9,1996-03-01,0.5792881103805376
Journal of Organic Chemistry,Ytterbium(III) Triflate-Catalyzed Amination of 1-Cyclopropylprop-2-yn-1-ols as an Expedient Route to Conjugated Enynes,Ytterbium(III) triflate-catalyzed ring opening of substituted 1-cyclopropyl-2-propyn-1-ols with sulfonamides as an efficient synthetic route to conjugated enynes is described herein. The reaction was operationally straightforward and accomplished in moderate to good yields and regioselective manner in all except one case under mild conditions.,10.1021/jo8024626,2009-01-07,0.5792870683707398
Tetrahedron,"Enantioselective [2,3] wittig ring contraction induced by chiral bases. The total synthesis and absolute configuration of (+)-aristolactone",,10.1016/s0040-4039(00)95502-3,1987-01-01,0.5792863746004318
Tetrahedron,"Intramolecular [4+2] cycloaddition of α,β-unsaturated hydrazones as a route to annelated pyridines",,10.1016/s0040-4039(00)82344-8,1988-01-01,0.5792859611445921
Synlett,Cytotoxic Alkaloids from Blue-Green Algae: A Total Synthesis of (-)-Didehydromirabazole A,"All articles of this category A concise total synthesis of the thiazole-thiazoline based metabolite (-)-didehydromirabazole A ( 2 ), a cytotoxic alkaloid isolated recently from the blue-green alga Scytonema mirabile , is described which uses sequential cyclocondensation reactions with methyl ( R )-2-methylcysteine hydrochloride ( 5 ) as key steps, viz 6 → 7 and 10 → 11 .",10.1055/s-1992-21406,1992-01-01,0.5792821539690233
Synthesis,Asymmetric Total Synthesis of (-)-Lupinine and (+)-Epilupinine via α-Sulfinyl Ketimine. Stereocontrolled Reduction of β-Sulfinyl Enamines,"All articles of this category (-)-Lupinine and (+)-epilupinine [(1 R ,9a R )- and (1 S , 9a R )-octahydro-1-hydroxymethyl-2 H -quinolizine] were synthesized from (+)-2,3,4,5-tetrahydro-6-[( R )-(4-methylphenyl)sulfinylmethyl]pyridine ( 4 ) in five steps. The intermediate, 3,4,6,7,8,9-hexahydro-1-[( R )-(4-methylphenyl)sulfinyl]-2 H -quinolizine ( 7 ), was stereoselectively reduced with cerium(III) chloride heptahydrate and sodium borohydride to give predominantly C-9a- R isomers, (9a R )-octahydro-1-[( R )-(4-methylphenyl)sulfinyl]-2 H -quinolizines.",10.1055/s-1991-26620,1991-01-01,0.5792801659117415
Synlett,One-step Reduction-Wittig Olefination of Methyl Pyroglutamate: Chiral Syntheses of (5S)-5-Alkenyl-2-pyrrolidinones and (S)-Vigabatrin®,All articles of this category An efficient methodology for the enantioselective synthesis of (5S)-5-alkenyl-2-pyrrolidinones was developed. The title chiral compounds were prepared starting from (5S)-methyl 1- t -butoxycarbonylpyroglutamate using three tandem reduction-Wittig olefination-oxidation reactions in 32-52% yield.,10.1055/s-1994-22848,1994-01-01,0.5792782758653958
Angewandte Chemie International Edition,Total Synthesis of the Triglycosyl Phenolic Glycolipid PGL‐tb1 from <i>Mycobacterium tuberculosis</i>,"Complex: The synthesis of the glycolipid PGL-tb1 present in the outer membrane of hypervirulent strains of Mycobacterium tuberculosis has been accomplished for the first time by using a highly convergent strategy featuring a Sonogashira coupling to unite a phenolic trisaccharide with the phthiocerol. Efficient asymmetric Cu-catalyzed 1,4-additions to unsaturated thioesters and cyclic enones have been employed to introduce the methyl groups.",10.1002/anie.201206221,2012-10-19,0.5792743117862489
European Journal of Organic Chemistry,Synthesis and Biological Profiling of Benzofuro‐Fused 7‐Deazapurine Nucleosides,"Abstract A series of benzofuro‐fused 7‐deazapurine (6 H ‐furo[2,3‐ e ]pyrimido[4,5‐ b ]indole) 2’‐deoxyribo‐ and ribonucleosides was designed and synthesized. The synthesis of key compound 10‐chloro‐6 H ‐furo[2,3‐ e ]pyrimido[4,5‐ b ]indole was based on the Negishi cross‐coupling of iodobenzofurane with zincated 4,6‐dichloropyrimidine followed by azidation and photochemical cyclization. Glycosylation of the heterocycle with either Hoffer's chlorodeoxyribose or protected ribose followed by cross‐coupling or substitution reactions at position 10 gave the desired two sets of final nucleosides that showed moderate to weak cytostatic activity and interesting fluorescence properties.",10.1002/ejoc.202300723,2023-09-21,0.5792724727033851
Tetrahedron,Organocatalytic route to the enantioselective synthesis of syn/anti-α-hydrazino-γ-fluoro alcohols,,10.1016/j.tetlet.2024.155179,2024-07-01,0.5792690540356201
Synthesis,"Synthesis of Dialkyl Phosphorocyanidites. Axial Preference of the<i>P</i>-Cyano Group in the 1,3,2-Dioxaphosphorinane Ring System",,10.1055/s-1975-23915,1975-01-01,0.5792678232150396
Organic Letters,"Enantioselective and Divergent Syntheses of Alstoscholarisines A, E and Their Enantiomers","Concise, enantioselective, and divergent syntheses of alstoscholarisines A and E are presented in 8 and 9 steps, respectively; alstoscholarisine E has never been accessed before. A boron-mediated aldol reaction and Rh-catalyzed cycloisomerization were exploited to access stereoisomers 8 and 9 as key intermediates. The challenging sterically congested alstoscholarisine core was furnished by a reductive transannular cyclization in the final steps. This strategy was also used for the syntheses of enantiomers of alstoscholarisines A and E.",10.1021/acs.orglett.8b02679,2018-09-20,0.579265988046949
Tetrahedron,An efficient and flexible approach for the synthesis of 4-demethoxy-daunomycinone and 4-demethoxy-11-deoxydaunomycinone,,10.1016/s0040-4039(00)81613-5,1983-01-01,0.5792637878483815
Organic Letters,Antitumor Agents. 274. A New Synthetic Strategy for E-Ring SAR Study of Antofine and Cryptopleurine Analogues,"A new versatile synthetic methodology for the synthesis of enantiomerically pure natural phenanthroindolizidines and phenanthroquinolizidines has been established and described. Natural products R-antofine and R-cryptopleurine, as well as a novel E-ring expanded analogue 13c (E7), 12-oxo-S-antofine (17), and 12N-methyl-12-aza-S-antofine (18) were synthesized with the new method. This strategy will greatly facilitate future SAR studies on the natural alkaloids with E-ring variations.",10.1021/ol902819j,2010-03-02,0.5792635539103372
Organic Letters,"A Practical, One-Pot Synthesis of Highly Substituted Thiophenes and Benzo[<i>b</i>]thiophenes from Bromoenynes and <i>o</i>-Alkynylbromobenzenes","An efficient synthesis of thiophenes and benzo[b]thiophenes has been developed from easily available bromoenynes and o-alkynylbromobenzene derivatives. This novel one-pot procedure involves a Pd-catalyzed C-S bond formation using a hydrogen sulfide surrogate followed by a heterocyclization reaction. Moreover, in situ functionalization with selected electrophiles further expands the potential of this methodology to the preparation of the corresponding highly substituted sulfur heterocycles.",10.1021/ol201970m,2011-09-01,0.579261268058261
Journal of Organic Chemistry,"Pyrimidine-Fused Heterocyclic Frameworks Based on an N4-Arylcytosine Scaffold: Synthesis, Characterization, and PNA Oligomerization of the Fluorescent Cytosine Analogue 5,6-BenzopC","A synthesis of an intrinsically fluorescent cytosine analogue 5,6-benzopC has been developed utilizing the reductive Ni-mediated cyclization of an N4-aryl,N4-(Boc)cytosine intermediate as a key step. 5,6-BenzopC was found to possess interesting fluorescence properties (Φ = 0.79, EtOH; Stoke's shift 113 nm). Peptide nucleic acid (PNA) oligomerization of the 5,6-benzopC monomer was carried out, followed by hybridization studies with complementary deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) which showed the modification to be well tolerated in the sequence contexts examined. Initial attempts to synthesize the heterocyclic skeleton present in 5,6-benzopC resulted in the discovery of routes to the pyrimido[1,6-a]benzimidazole, pyrimido[1,6-a]quinazoline, and pyrimido[1,6-a]benzo[b]6-bora-1,3-diazine heterocyclic frameworks.",10.1021/jo402873e,2014-03-25,0.5792452251803891
Synthesis,Synthetic Studies on Ecteinascidin 743 (Et 743): Asymmetric Synthesis of a Highly Oxygenated Tetrahydroisoquinoline via a Key Phenolic Mannich Reaction,"A concise synthesis of a highly functionalized, orthogonally protected amino triol I (R = CH2Ph, R1 = SiPh2CMe3) was achieved via a Mannich reaction between a corresponding phenol II and a chiral oxazinone III as a key step. The utility of such an approach is illustrated by a concise synthesis of a highly oxygenated tetrahydroisoquinoline IV (R = CH2Ph), a key structural unit of ecteinascidin 743 (Et 743) and related natural products. [on SciFinder (R)]",10.1055/s-2006-950343,2006-12-01,0.579242174630479
Organic Letters,N–N Bond Formation between Primary Amines and Nitrosos: Direct Synthesis of 2-Substituted Indazolones with Mechanistic Insights,"A concise, one-step route to indazolones from primary alkyl amines and o-nitrobenzyl alcohols is reported. The key step in this readily scalable indazolone forming process involves base-mediated in situ o-nitrobenzyl alcohol → o-nitrosobenzaldehyde conversion. Although this functional group interconversion is known to be useful for 2 H-indazole synthesis, its reactivity was modulated for indazolone formation.",10.1021/acs.orglett.8b01655,2018-08-01,0.5792420035388133
Tetrahedron,Aminohaloborane in organic synthesis. VIII. A one-step synthesis of 2-Aminobenzhydrols from anilines,,10.1016/s0040-4039(00)71405-5,1980-01-01,0.5792405851402787
Journal of Organic Chemistry,"Using Heteroaryl-lithium Reagents as Hydroxycarbonyl Anion Equivalents in Conjugate Addition Reactions with (<i>S</i>,<i>S</i>)-(+)-Pseudoephedrine as Chiral Auxiliary; Enantioselective Synthesis of 3-Substituted Pyrrolidines","We have developed an efficient protocol for carrying out the stereocontrolled formal conjugate addition of hydroxycarbonyl anion equivalents to α,β-unsaturated carboxylic acid derivatives using (S,S)-(+)-pseudoephedrine as chiral auxiliary, making use of the synthetic equivalence between the heteroaryl moieties and the carboxylate group. This protocol has been applied as key step in the enantioselective synthesis of 3-substituted pyrrolidines in which, after removing the chiral auxiliary, the heteroaryl moiety is converted into a carboxylate group followed by reduction and double nucleophilic displacement. Alternatively, the access to the same type of heterocyclic scaffold but with opposite absolute configuration has also been accomplished by making use of the regio- and diastereoselective conjugate addition of organolithium reagents to α,β,γ,δ-unsaturated amides derived from the same chiral auxiliary followed by chiral auxiliary removal, ozonolysis, and reductive amination/intramolecular nucleophilic displacement sequence.",10.1021/jo302438k,2012-12-21,0.5792385970430455
Synlett,First Total Synthesis of (+)-11-Hydroxyerythratidine,"The first total synthesis of (+)-11-hydroxyerythratidine is described. The strategy is featured by a highly stereoselective construction of the C(5) spiro center via the Lewis acid promoted cyclization of ortho-quinone acetal, derived from di-ortho-substituted biphenyl 9 with a chiral center at the side chain.",10.1055/s-0028-1088157,2009-03-26,0.57923344544129
Tetrahedron,Stereospecific rearrangement of α-hydroxyepoxide: efficient approach to the trans-bicyclo[9.3.0]tetradecane core en route to clavulactone,,10.1016/j.tetlet.2005.11.021,2005-11-30,0.579230224464025
Journal of Organic Chemistry,Total Synthesis of Quinaldopeptin and Its Analogues,"The first total synthesis of quinaldopeptin (1) was accomplished. Our approach to the synthesis of 1 includes the solid-phase peptide synthesis of the linear decapeptide 4 followed by macrocyclization and introduction of the quinoline chromophores 2 at a late stage of the synthesis. As for the preparation of 4, a fragment coupling approach was applied considering the C2 symmetrical structure of 1. Chromophore analogues 22 and 23 and desmethyl analogue 27 were also prepared in a manner similar to the synthesis of 1. Synthetic 1 exhibits a strong cytotoxicity with the IC50 value of 3.2 nM. On the other hand, the activity of 23 and 27 was largely reduced.",10.1021/jo402267r,2013-11-15,0.5792294163798143
Journal of Organic Chemistry,"Synthesis of Tuckolide, a New Cholesterol Biosynthesis Inhibitor","Tuckolide (decarestrictine D), a 10-membered lactone isolated from P. corylophilum and polyporus tuberaster fungi that potently inhibits cholesterol biosynthesis, was synthesized. The key steps include a Sharpless catalytic asymmetric dihydroxylation reaction (AD) of the methoxymethyl (MOM) ether protected diene 2 and a direct Corey-Nicolaou lactonization reaction of seco-acid 1with added silver perchlorate. The selectivity of the dihydroxylation step was found to be highly dependent on the nature of the protecting group adjacent to the diene in 2. The selectivity of the asymmetric dihydroxylation reaction of 2 indicates that both steric and electronic effects can lead to significant amounts of the undesired isomers. This synthesis establishes the absolute stereochemistry of tuckolide showing the C3 hydroxyl bearing carbon with an S-configuration comparable in an absolute sense to that in the lactone portion of the HMG-CoA reductase inhibitor compactin.",10.1021/jo961686+,1996-01-01,0.5792287227165953
Synthesis,Synthesis of α-Imino Oximes from α-Hydroxyimino Ketones,"All articles of this category The facile synthesis of a series of novel α-imino oximes from 1,2-dicarbonyl compounds is described. The route involves titanium(IV) chloride catalyzed condensation of amines to the stable and readily available monooximes of 1,2-dicarbonyl compounds.",10.1055/s-1989-27283,1989-01-01,0.579228098383541
European Journal of Organic Chemistry,Total Synthesis of an Anticancer Natural Product (±)‐Peharmaline A and Its Analogues,First total synthesis of a rare β‐carboline–vasicinone hybrid alkaloid (±)‐peharmaline A has been accomplished in just 3 steps starting from known compounds. Stereoselective Pictet–Spengler reaction to nitrogenated tertiary carbon center and one‐pot construction of the tricyclic skeleton of vasicinone are the highlights of present synthesis. We have also synthesized structurally close analogues of the natural product by following the developed route.,10.1002/ejoc.201800949,2018-09-21,0.5792265582164275
Tetrahedron,Tamaru reaction-based approach towards the synthesis of muscone and analogues using renewable sources,"Muscone is considered as the king of fragrances, due to its rare occurrence and exotic nature, many attempts have been made to synthesise musk analogues. The presence of methyl group at the C-3 position from ketone imparts the musk character to the molecule. The Tamaru reaction (Ni-catalysed reductive coupling of aldehyde and 1,3-dienes) is used as the key step for the installation of the methyl group in an efficient manner to afford the RCM precursor diene. A short three step sequence involving oxidation , RCM and reduction gave a highly efficient access to muscone and analogues. Both the precursors, namely, the aldehyde and isoprene are derived from renewable resource.",10.1016/j.tetlet.2025.155593,2025-04-18,0.5792236994831146
European Journal of Organic Chemistry,Asymmetric Synthesis of Isocarbacyclin Based on the Olefination-Isomerization-Coupling Process with Chiral Sulfoximines,"An asymmetric synthesis of isocarbacyclin (2) was achieved from ketone 7 by the olefination-isomerization-coupling process with chiral sulfoximines. The vinylic sulfoximine 6 (≥98% de) was prepared from ketone 7 and lithiosulfoximine 8 by an asymmetric olefination via an addition-elimination process. Model experiments, aiming at a rationalization of the asymmetric induction in the elimination of β-hydroxysulfoximines, with ketone 12 and lithiosulfoximine ent-8 revealed formation of the silyl ether 15 as an intermediate which eliminated LiOSiMe3 upon reaction with nBuLi under formation of (S,Z)-alkene 17 (≥98% de). Reaction of the C, O-dilithiosulfoximine 19 with ClSiMe3 led to elimination of LiOSiMe3 and also gave 17 (≥98% de). Methylation of 19, however, furnished the corresponding α-methyl-substituted β-hydroxysulfoximines, 20 and 21, in a ratio of 75:25. Isomerization of sulfoximine 6 gave the allylic sulfoximine 5 (96% de) whose absolute configuration was determined by X-ray structure analysis. Cross-coupling reaction of 5 with cuprate 23 delivered with high regioselectivity alkene 25. A similar reaction of 5 with the organocopper reagent 26, which was prepared from (benzyloxy)methylmagnesium chloride, in the presence of BF3 · OEt2 and halide afforded alkene 27. Ketone 28 is a potential starting material for the asymmetric synthesis of 3-oxaisocarbacyclin. Besides alkenes 25 and 27 sulfinamide 24 (97% ee), whose conversion to 8 has been already described, was isolated in 90% yield. The key step in the sequence leading to the construction of the ω-side chain was the deprotonation of ketone 4b with a complex of lithium (R,R)-bis(α-phenylethyl)amide and lithium chloride, 29 · LiCl, which gave enolate 3. The use of ent-29 · LiCl in the deprotonation of 4b afforded the isomeric enolate 30. Enolates 3 and 30 were trapped as the silyl ethers 31 (90% ie) and 32 (92% ie), respectively. The aldol reaction of 3 with (E)-octenal proceeded highly selective in regard to C-12 but unselective in regard to C-13 and gave aldols 34 (42%) and epi-34 (36%). It was at the stage of the aldol reaction of 3 where the unwanted diastereomers 35 and epi-35, stemming from 30, could be separated. Reduction of ketones 34 and epi-34 afforded diols 36 (≥98% de) and 37 (93% de), respectively. The Pd-catalyzed rearrangement of the allylic diacetates 39 and 41 was highly stereoselective (≥98% de) but incomplete and led to formation of mixtures of 40 and 39 as well as of 42 and 41 in ratios of 84:16 and 86:14, respectively. A two-step oxidation of alcohol 43, contaminated by 5% of the isomeric alcohol stemming from acetate 39, via aldehyde 44 gave after purification by crystallization isocarbacyclin (2) in 38% yield. Diol 45, having the undesired (15R) configuration, was selectively oxidized with dichlorodicyanobenzoquinone to enone 46 (81%).",10.1002/(sici)1099-0690(199807)1998:7<1319::aid-ejoc1319>3.0.co;2-l,1998-07-01,0.5792221016705201
European Journal of Organic Chemistry,Asymmetric Synthesis of Isocarbacyclin Based on the Olefination-Isomerization-Coupling Process with Chiral Sulfoximines,"An asymmetric synthesis of isocarbacyclin (2) was achieved from ketone 7 by the olefination-isomerization-coupling process with chiral sulfoximines. The vinylic sulfoximine 6 (≥98% de) was prepared from ketone 7 and lithiosulfoximine 8 by an asymmetric olefination via an addition-elimination process. Model experiments, aiming at a rationalization of the asymmetric induction in the elimination of β-hydroxysulfoximines, with ketone 12 and lithiosulfoximine ent-8 revealed formation of the silyl ether 15 as an intermediate which eliminated LiOSiMe3 upon reaction with nBuLi under formation of (S,Z)-alkene 17 (≥98% de). Reaction of the C, O-dilithiosulfoximine 19 with ClSiMe3 led to elimination of LiOSiMe3 and also gave 17 (≥98% de). Methylation of 19, however, furnished the corresponding α-methyl-substituted β-hydroxysulfoximines, 20 and 21, in a ratio of 75:25. Isomerization of sulfoximine 6 gave the allylic sulfoximine 5 (96% de) whose absolute configuration was determined by X-ray structure analysis. Cross-coupling reaction of 5 with cuprate 23 delivered with high regioselectivity alkene 25. A similar reaction of 5 with the organocopper reagent 26, which was prepared from (benzyloxy)methylmagnesium chloride, in the presence of BF3 · OEt2 and halide afforded alkene 27. Ketone 28 is a potential starting material for the asymmetric synthesis of 3-oxaisocarbacyclin. Besides alkenes 25 and 27 sulfinamide 24 (97% ee), whose conversion to 8 has been already described, was isolated in 90% yield. The key step in the sequence leading to the construction of the ω-side chain was the deprotonation of ketone 4b with a complex of lithium (R,R)-bis(α-phenylethyl)amide and lithium chloride, 29 · LiCl, which gave enolate 3. The use of ent-29 · LiCl in the deprotonation of 4b afforded the isomeric enolate 30. Enolates 3 and 30 were trapped as the silyl ethers 31 (90% ie) and 32 (92% ie), respectively. The aldol reaction of 3 with (E)-octenal proceeded highly selective in regard to C-12 but unselective in regard to C-13 and gave aldols 34 (42%) and epi-34 (36%). It was at the stage of the aldol reaction of 3 where the unwanted diastereomers 35 and epi-35, stemming from 30, could be separated. Reduction of ketones 34 and epi-34 afforded diols 36 (≥98% de) and 37 (93% de), respectively. The Pd-catalyzed rearrangement of the allylic diacetates 39 and 41 was highly stereoselective (≥98% de) but incomplete and led to formation of mixtures of 40 and 39 as well as of 42 and 41 in ratios of 84:16 and 86:14, respectively. A two-step oxidation of alcohol 43, contaminated by 5% of the isomeric alcohol stemming from acetate 39, via aldehyde 44 gave after purification by crystallization isocarbacyclin (2) in 38% yield. Diol 45, having the undesired (15R) configuration, was selectively oxidized with dichlorodicyanobenzoquinone to enone 46 (81%).",10.1002/(sici)1099-0690(199807)1998:7<1319::aid-ejoc1319>3.3.co;2-c,1998-07-01,0.5792221016705201
Chemical Science,Asymmetric total synthesis of glauconic and glaucanic acid,"-Evans aldol reaction and an asymmetric 1,4-addition to set the three contiguous stereocenters. A key intramolecular alkylation reaction was utilized to forge the nine-membered carbocycle and install the quaternary stereocenter with excellent diastereoselectivity. The unexpectedly high diastereoselectivity of the cyclization led us to perform a more detailed conformational analysis. A computational pipeline consisting of fast conformer generation and high-level quantum-molecular calculations was uniquely suitable to describe the conformationally-rich nine-membered ring formation and gave insights into key interactions in the favored transition states. The highly robust and scalable route allowed for the preparation of multi-gram quantities of an advanced nine-membered carbocyclic intermediate which served as a basis for the late-stage installation of the two cyclic anhydride moieties ultimately leading to glauconic and glaucanic acid. Moderate herbicidal activity against a range of mono- and dicotyledonous weeds could be demonstrated for glauconic acid.",10.1039/d4sc08332f,2025-01-01,0.5792215008326278
Organic Letters,"Synthesis of Demissidine by a Ring Fragmentation 1,3-Dipolar Cycloaddition Approach","A synthesis of the steroidal alkaloid demissidine from epiandrosterone is reported. A ring fragmentation reaction that efficiently ruptured the D-ring of a diazo ester derivative of epiandrosterone to provide an aldehyde tethered ynoate product was key to this sequence. Incorporation of the indolizidine framework was achieved by an azomethine ylide 1,3-dipolar cycloaddition.",10.1021/ol4004993,2013-04-15,0.5792212964746385
Organic Letters,Stereocontrolled Synthesis of the Portimine Skeleton via Organocatalyst-Mediated Asymmetric Stannylation and Stereoretentive C(<i>sp</i><sup>3</sup>)–C(<i>sp</i><sup>2</sup>) Stille Coupling,High Resolution Image Download MS PowerPoint Slide Our efforts toward the synthesis of the marine natural product portimine are described. The key to the synthesis of the skeleton is a stereoretentive copper-catalyzed C( sp 3 )–C( sp 2 ) Stille-type cross-coupling that enables the convergent assembly of functionalized fragments. The core skeleton of portimine was constructed via ring-closing metathesis and transannular acetal formation.,10.1021/acs.orglett.4c04245,2025-01-22,0.5792192804918656
Chemical Science,Tandem Peterson olefination and chemoselective asymmetric hydrogenation of β-hydroxy silanes,Tandem Peterson olefination and asymmetric hydrogenation of β-hydroxy silanes provides an efficient route to access the chiral benzylic hydrocarbon. The chemoselectivity can be tuned by the addition of base.,10.1039/c8sc05261a,2019-01-01,0.5792173842023002
Synthesis,"Synthesis of Enantiopure 1,2-Didehydropyrrolidine, D-Proline, and Oxazoline Derivatives via Staudinger-Aza-Wittig Cyclization of γ-Azido Aldehydes","All articles of this category The synthesis of 3-, 3,5- and 3,4,5-substituted prolines 1 and oxazolines 3 from inexpensive D-mannitol, employing the Staudinger-Aza-Wittig cyclization as a key step, is described. peptidomimetics - Staudinger cyclization - oxazoline - cyanosilylation - cyclic imines",10.1055/s-1996-4162,1996-01-01,0.5792154628325134
European Journal of Organic Chemistry,Double Asymmetric Induction in Organocatalyzed Aldol Reactions: Total Synthesis of (+)‐2‐<i>epi</i>‐Hyacinthacine A<sub>2</sub> and (–)‐3‐<i>epi</i>‐Hyacinthacine A<sub>1</sub>,"Abstract The stereodivergent synthesis of two hyacinthacine analogues, which relies on an organocatalyzed aldol addition, is described. The aldol addition of dioxanone to an α‐ N ‐carbobenzyloxy‐substituted chiral aldehyde, promoted by both ( R )‐ and ( S )‐proline, proceeds in reasonable yields with acceptable diastereomeric ratios. The success of the reaction may be due to the use of an acyclic aldehyde acceptor, which allows reagent control of the stereochemical outcome of the key aldolization step in both the matched and mismatched cases.",10.1002/ejoc.201300716,2013-07-18,0.5792148344212218
Tetrahedron,"Novel synthesis of oxonine derivatives from 3-[(2-aminophenyl)amino]-5,5-dimethyl-2-cyclohexene-1-one and o-quinones",,10.1016/j.tetlet.2011.10.147,2011-11-05,0.5792134351842777
Journal of Organic Chemistry,Amination of <i>N</i>-Aryl Prolinol via Ring Expansion and Contraction:  Application to the Chiral Ligand for the Catalytic Asymmetric Reaction,"Chiral diaminophosphines 4 were prepared from (S)-prolinol-derived aminophosphine oxide 5 by bromination with ring expansion followed by amination with ring contraction and reduction, using trichlorosilane. In the presence of 4 as a ligand, palladium-catalyzed asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl acetate (11) with a dialkyl malonate-BSA-LiOAc system was successfully carried out with good enantioselectivities (up to 98% ee).",10.1021/jo0479967,2005-02-05,0.5792046450327152
European Journal of Organic Chemistry,Enantioselective Synthesis of Planar Chiralortho-Functionalized Ferrocenyl Ketones,"An efficient and flexible asymmetric synthesis of planar chiral ortho-functionalized ferrocenyl ketones in good overall yields (35−79%) and enantiomeric excesses (ee = 71−96%) is described. The key step of the procedure is the diastereoselective (de = 87−98%) orthometalation of ferrocenyl ketone SAMP hydrazones, followed by trapping with various electrophiles such as MeI, Me3SiCl, Ph2PCl, Ph2CO, Me2NCHO or I2. Subsequent oxidative or reductive hydrazone cleavage leads to the title compounds.",10.1002/1099-0690(200008)2000:16<2839::aid-ejoc2839>3.0.co;2-q,2000-08-01,0.5792022994994616
Organic Process Research & Development,Safety vs Efficiency in the Development of a High-Energy Compound,"A scalable route to 5-(2-carboxy-pyridin-2-yloxy)-benz[1,2,5]oxadiazole ( 3 ) is demonstrated. The synthesis was designed to minimize potential safety issues with a previously practiced route and, in particular, to avoid the handling of 5-hydroxybenzofurazan, which was found to decompose with a large energy release at relatively low temperatures. The new route builds the benzofurazan moiety onto a nicotinonitrile core to avoid high-energy intermediates with low onset temperatures of decomposition.",10.1021/op0341059,2003-10-01,0.5792022889390234
Journal of Organic Chemistry,Synthesis of Sugar Diene and Its Pd-Catalyzed Transformation into Chromanes,"A route to synthesize 1,2-disubstituted glucals has been developed, which were further converted to substituted chromanes by thermal 6π-electrocyclization in HMPA followed by in situ aromatization. One of the key steps in the synthesis of chromane is metal-free generation of C1-substituted glucal from d-mannose, which was further converted to 1,2-disubstituted glucals by Pd-catalyzed Fujiwara-Moritani reaction with styrenes, acrylates, acrylamide, acrylonitrile, and ethyl vinyl ketone in good yields.",10.1021/acs.joc.0c00432,2020-05-13,0.5791989130294894
Tetrahedron,Palladium-catalyzed asymmetric cyclization of methyl (E)-oxo-9-phenoxy-7-nonenoate and its analogs,,10.1016/s0040-4039(00)87540-1,1982-01-01,0.5791945714139053
Tetrahedron,Further studies on the acetonedicarboxylate route to thienamycin—stereochemical inversion at the lactone stage.,,10.1016/0040-4039(81)89007-7,1981-01-01,0.5791934148965255
Organic Letters,Enantioselective Cyclopropanation of Indoles: Construction of All-Carbon Quaternary Stereocenters,"The first enantioselective copper-catalyzed cyclopropanation of N-acyl indoles is described. Using carbohydrate-based bis(oxazoline) ligands (glucoBox), the products were obtained in up to 72% ee. Cyclopropanation of N-Boc 3-methyl indole yielded a product with an all-carbon quaternary stereocenter, which is a valuable building block for the synthesis of indole alkaloids: Deprotection and rearrangement gave a tricyclic hemiaminal ester in 96% ee, which was subsequently employed as a key intermediate for the synthesis of (-)-desoxyeseroline.",10.1021/ol302388t,2012-09-25,0.5791865463062348
Tetrahedron,"Synthesis of the C6C16 polyene fragment of ratjadone, a potent cytotoxic metabolite from Sorangium cellulosum",,10.1016/s0040-4039(99)00716-9,1999-05-01,0.5791845011788976
Tetrahedron,"A short convergent synthesis of the side chains of brassinolide, cathasterone, and cryptolide",,10.1016/j.tetlet.2012.11.094,2012-11-29,0.5791802589349035
Tetrahedron,A short and convergent synthesis of unsaturated macrodilactones,,10.1016/s0040-4039(00)70707-6,1989-01-01,0.5791802589349035
Tetrahedron,"Convergent, short synthesis of the muscarinic superagonist iperoxo",,10.1016/j.tetlet.2010.04.130,2010-05-08,0.5791802589349035
Journal of Organic Chemistry,Divergence en Route to Nonclassical Annonaceous Acetogenins. Synthesis of Pyranicin and Pyragonicin,"Syntheses of the nonclassical annonaceous acetogenins, pyranicin, and pyragonicin from common late-stage intermediates are presented. The construction of key elements relies on asymmetric HWE reactions, including the desymmetrization of a meso-dialdehyde and a parallel kinetic resolution of a racemic aldehyde. A stereoconvergent Pd-catalyzed substitution serves to install the C4 stereocenter in protected form with different orthogonal protective groups. A divergent strategy to form 1,4- and 1,6-diols, employing stereoselective Zn-mediated alkynylations, is used for completion of the core structures. Notably, the stereoselective coupling reaction toward pyragonicin proceeds with highly functionalized fragments. The methodology is further expanded by a divergent synthesis of all stereoisomers of the 2,3,6-trisubstituted tetrahydropyran subunit.",10.1021/jo052233k,2006-02-02,0.5791800297901387
Angewandte Chemie International Edition,"The Spongistatins: Architecturally Complex Natural Products—Part Two: Synthesis of the C(29–51) Subunit, Fragment Assembly, and Final Elaboration to (+)-Spongistatin 2",An advanced ABCD fragment (see picture) constructed on the way to the total synthesis of the potent antitumor agent (+)-spongistatin 2 has also been used in a formal total synthesis of (+)-spongistatin 1. In both cases the critical step was an acid-mediated epimerization in the presence of Ca2+ ions to stabilize the axial–equitorial CD spiroketal.,10.1002/1521-3773(20010105)40:1<196::aid-anie196>3.3.co;2-k,2001-01-05,0.5791737125223766
Angewandte Chemie International Edition,"The Spongistatins: Architecturally Complex Natural Products-Part Two: Synthesis of the C(29-51) Subunit, Fragment Assembly, and Final Elaboration to (+)-Spongistatin 2",An advanced ABCD fragment (see picture) constructed on the way to the total synthesis of the potent antitumor agent (+)-spongistatin 2 has also been used in a formal total synthesis of (+)-spongistatin 1. In both cases the critical step was an acid-mediated epimerization in the presence of Ca2+ ions to stabilize the axial–equitorial CD spiroketal.,10.1002/1521-3773(20010105)40:1<196::aid-anie196>3.0.co;2-t,2001-01-04,0.5791737125223766
Tetrahedron,Asymmetric synthesis of (R) and (S)-4-hydroxy-2-cyclohexenone and derivatives,,10.1016/s0040-4039(00)97138-7,1990-01-01,0.5791729107484258
Tetrahedron,Efficient tin-mediated synthesis of lysophospholipid conjugates of a TLR7/8-active imidazoquinoline,,10.1016/j.tetlet.2016.03.110,2016-04-03,0.5791727505788791
Organic Letters,Total Synthesis of Gambierol,"[structure: see text] The first total synthesis of gambierol, a marine polycyclic ether toxin, has been achieved. The synthesis features the Pd(PPh3)4/CuCl/LiCl-promoted Stille coupling for the stereoselective construction of the sensitive triene side chain that includes a conjugated (Z,Z)-diene moiety.",10.1021/ol026394b,2002-07-19,0.5791679443977222
Tetrahedron,An efficient one-pot synthesis of substituted 2-arylbenzo[b]thiophene derivatives,,10.1016/s0040-4039(03)01632-0,2003-08-01,0.5791604756538851
Organic Letters,Total Syntheses of (−)-Spirooliganones A and B,"The enantioselective syntheses of (-)-spirooliganones A and B have been accomplished in eight steps from commercially available starting materials. Noteworthy transformations include a three-component hetero-Diels-Alder cycloaddition to construct the tetracyclic core of spirooliganones, a Sharpless asymmetric dihydroxylation, and a tandem oxidative dearomatization/cyclization to build the oxa-spiro cyclohexadienone skeleton. The straightforward syntheses were performed without protecting groups.",10.1021/ol501050s,2014-05-02,0.5791588503352968
Tetrahedron,Synthetic studies on siccanin. Efficient construction of the cis-fused drimane unit and synthesis of isosiccanin methyl ether,,10.1016/s0040-4039(00)82438-7,1988-01-01,0.5791584941862425
Synthesis,"An Efficient and General Synthesis of 5′-Esters of 2′,3′-Didehydro-2′,3′-dideoxynucleosides: A Facile Opening of 2′,3′-Orthoacetates of Ribonucleosides Followed by Reductive Elimination of the Halogenoacetates","All articles of this category A three-step reaction sequence starting from a ribonucleoside to give the corresponding 5′- O -acyl-2′,3′-didehydro-2′,3′-dideoxynucleoside is described. The key intermediate is the bromoacetate, made by reaction of the 2′,3′-methoxyethylidene nucleoside with acetyl bromide. Reductive elimination of the bromoacetate using a zinc-copper couple furnishes the desired compounds in good overall yield.",10.1055/s-1993-25853,1993-01-01,0.5791494651651037
Synlett,Total Synthesis of (–)-HM-3 and (–)-HM-4 Utilizing a Palladium-Catalyzed Addition of an Arylboronic Acid to an Allenic Alcohol Followed by Eschenmoser–Claisen Rearrangement,"The first asymmetric total synthesis of (–)-HM-3 and (–)-HM-4, aromatic sesquiterpenes isolated from the phytopathogenic fungus Helicobasidium mompa , has been achieved. Highlight of the synthesis is an enantiospecific construction of the quaternary carbon stereocenter utilizing a palladium-catalyzed addition of arylboronic acid to the allenic alcohol followed by Eschenmoser–Claisen rearrangement.",10.1055/s-0033-1341059,2014-04-03,0.5791468509061269
Tetrahedron,Regioselective synthesis of 4-(2-alkyl-5-methyl-2H-pyrazol-3-yl)-piperidines,,10.1016/j.tetlet.2006.01.044,2006-02-04,0.5791457481722954
Tetrahedron,New synthetic route to access (±) salinosporamide A via an oxazolone-mediated ene-type reaction,,10.1016/j.tetlet.2008.10.154,2008-11-12,0.5791357003477097
Angewandte Chemie International Edition,The Synthesis of Structurally Diverse Macrocycles By Successive Ring Expansion,"Structurally diverse macrocycles and medium-sized rings (9-24 membered scaffolds, 22 examples) can be generated through a telescoped acylation/ring-expansion sequence, leading to the insertion of linear fragments into cyclic β-ketoesters without performing a discrete macrocyclization step. The key β-ketoester motif is regenerated in the ring-expanded product, meaning that the same sequence of steps can then be repeated (in theory indefinitely) with other linear fragments, allowing macrocycles with precise substitution patterns to be ""grown"" from smaller rings using the successive ring-expansion (SuRE) method.",10.1002/anie.201509153,2015-11-13,0.5791273903956349
European Journal of Organic Chemistry,Further Synthetic Studies Towards the Austrodorane Skeleton: Synthesis of Austrodoral,"Abstract The synthesis of austrodoral ( 1 ), a marine nor ‐sesquiterpene that contains a unique bicyclic skeleton, has been achieved. The synthetic strategy is based on the ring contraction of a suitable optically active drimanic epoxy derivative, obtained from commercially available (+)‐sclareolide ( 4 ). Fluorosulfonic acid was found to promote the ring contraction efficiently. The nor ‐sesquiterpene hydrocarbon 13 , a key intermediate in the synthesis of sesquiterpene hydroquinones, has also been prepared in optically active form. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2005)",10.1002/ejoc.200400795,2005-04-25,0.5791231800666864
Organic Letters,Synthesis of α-Halo-γ-hydroxyenamides by Titanium Tetrahalide Mediated Addition of Aldehydes or Ketones to Ynamides,"α-Chloro- or α-bromo-γ-hydroxyenamides were synthesized by the reaction of an ynamide, titanium tetrahalide, and an aldehyde or a ketone. A γ-hydroxy trisubstituted enamide was prepared stereoselectively by Suzuki coupling of an obtained α-chloro-γ-hydroxyenamide with phenyl boronic acid. Intramolecular cyclization of α-chloro-γ-hydroxyenamide took place to provide a 2,3-dihydrobenzoisothiazole 1,1-dioxide derivative by palladium-catalyzed C-H activation of the tosyl group. Hydrochlorination of ynamides proceeded to give α-chloroenamides by treatment with titanium tetrachloride followed by addition of water.",10.1021/acs.orglett.6b02526,2016-09-20,0.5791120615064923
Journal of Organic Chemistry,A Highly Diastereoselective Synthesis of α-Hydroxy-β-amino Acid Derivatives via a Lewis Acid Catalyzed Three-Component Condensation Reaction,"A very efficient three-component synthesis of a series of syn α-hydroxy-β-amino esters, obtained in high diastereoselection and yield, was realized starting from an aldehyde, benzylamine, and the ketene silyl acetals derived from Ley's lactones. The synthetic protocol was optimized and the above compounds were obtained without the isolation of intermediates. The origin of the observed diastereoselection was investigated through a computational model of the key reaction step.",10.1021/jo1011762,2010-10-14,0.579112057492719
Tetrahedron,"An expedient route to the tricyclic pyridone derivative Ro 41-3696, a novel non-benzodiazepine sleep inducer",,10.1016/0040-4039(95)00387-r,1995-04-01,0.5791105733828518
Journal of the American Chemical Society,Total Syntheses of Giraldine I and Heterophyllisine,"Aconitine and related norditerpenoid alkaloids are chemically and biologically significant natural products that represent a formidable synthetic challenge. Here, we report the first total syntheses of aconitine-type alkaloid giraldine I and lactone-type alkaloid heterophyllisine. Key strategies include (1) early stage installation of the C4 all-carbon quaternary stereocenter and nitrogen atom via allene hydrocyanation, (2) skeletal editing through hydrodealkenylative fragmentation/Mannich cyclization to build the A/B/E/F tetracyclic scaffold, (3) a Claisen rearrangement/ring-closing metathesis (RCM) sequence followed by transannular pinacol coupling to form the characteristic C/D rings of aconitines, and (4) a bioinspired and regioselective Baeyer-Villiger oxidation to access the lactone-type alkaloid.",10.1021/jacs.5c14513,2025-10-01,0.5791048693750386
Tetrahedron,Phosphonic acid catalyzed synthesis of pyrazolidines,,10.1016/j.tetlet.2011.11.083,2011-11-22,0.5790976896187734
Journal of the American Chemical Society,Full Stereochemical Determination of Ajudazols A and B by Bioinformatics Gene Cluster Analysis and Total Synthesis of Ajudazol B by an Asymmetric Ortholithiation Strategy,"The stereochemical determination of the potent respiratory chain inhibitors ajudazols A and B and the total synthesis of ajudazol B are reported. Configurational assignment was exclusively based on biosynthetic gene cluster analysis of both ketoreductase domains for hydroxyl-bearing stereocenters and one of the first predictive enoylreductase alignments for methyl-bearing stereocenters. The expedient total synthesis resulting in unambiguous proof of the predicted stereochemistry involves a short stereoselective approach to the challenging isochromanone stereotriad by an innovative asymmetric ortholithiation strategy, a modular oxazole formation, and a late-stage Z,Z-selective Suzuki coupling.",10.1021/ja309685n,2012-11-05,0.5790950108378083
Journal of Organic Chemistry,Synthesis of a Series of Focally-Substituted Organothiol Dendrons,The synthesis of new organothiol-functionalized dendrons of generation 1−4 is described. Several modifications to the original method for preparation of dendrons are detailed that were found to improve the yield and aid in scale-up. A particularly advantageous method for preparation of an aromatic thiol is reported and is employed in this reaction sequence. Several uses of these dendrons are anticipated and briefly described.,10.1021/jo961527q,1996-01-01,0.5790949589900001
Tetrahedron,"A novel carbanion-olefin intramolecular cyclization: synthesis of substituted 2-aroyl-3,4-dihydro-2H-benzopyrans from salicylaldehydes",,10.1016/j.tetlet.2009.07.132,2009-08-07,0.5790928899064853
Tetrahedron,"The synthesis of 2,6,7,11-tetraphenylisobenzofuran[b]cyclobutadiene: A new stable antiaromatic compound",,10.1016/s0040-4039(01)94969-x,1978-01-01,0.5790911078368821
Journal of Organic Chemistry,Asymmetric Synthesis of <i>cis</i>-2-Aminocyclopropanols by Intramolecular Mannich Addition of Silyloxy Benzyl Carbanions,"An efficient, highly diastereoselective method for the preparation of protected cis-2-aminocyclopropanols from N-tert-butanesulfinyl ketimines and various aryl acylsilanes is described. A tandem process for carbon-carbon bond formation via nucleophilic addition to acylsilanes, Brook rearrangement, and intramolecular Mannich reaction has been developed.",10.1021/jo200585r,2011-04-29,0.5790811257598972
Tetrahedron,Regiospecific acylation of organocopper enolates: a new synthesis of 7-oxoprostaglandins,,10.1016/0040-4039(75)85004-0,1975-05-01,0.579077731633426
Tetrahedron,Regiospecific acylation of organocopper enolates: A new synthesis of 7-oxoprostaglandins,,10.1016/s0040-4039(00)72190-3,1975-01-01,0.579077731633426
Journal of the American Chemical Society,Palladium-Catalyzed Asymmetric Allylic Alkylation of 2-Acylimidazoles as Ester Enolate Equivalents,"A broad range of highly enantioenriched 2-acylimidazoles are synthesized by palladium-catalyzed decarboxylative asymmetric allylic alkylation (DAAA) of 2-imidazolo-substituted enol carbonates. The enantioenriched 2-acylimidazole products can easily be converted to the corresponding carboxylic acid, ester, amide, and ketone derivatives with complete retention of the enantiopurity. The synthetic utility of this new method is demonstrated in the short, efficient synthesis of cetiedil.",10.1021/ja103771w,2010-06-15,0.5790767891404475
Journal of the American Chemical Society,Total Synthesis and Structural Revision of Vannusals A and B: Synthesis of the True Structures of Vannusals A and B,"Having determined through total synthesis that the originally assigned structure of vannusals A and B were incorrect, we set out to uncover the identity of the true structures of these novel marine natural products. Our search was based on intelligence gathered by NMR spectroscopy and chemical synthesis and took us through the total synthesis of eight diastereomeric vannusal B structures [2, d-2, 3, d-3, 4, d-4, 5, and d-5, Figure 2]. The true structures of vannusals A and B were finally determined to be d-5 and d-1, respectively. Their total synthesis was based on a highly convergent and efficient strategy that involved fragments vinyl iodide (-)-6 and aldehyde (+/-)-94, and featured a stereoselective lithium-mediated coupling reaction and a samarium-induced cyclization process that forged the final ring of the carbon framework. The synthetic strategies and technologies developed in these investigations expand the scope of chemical synthesis and render these compounds readily available for biological evaluation, while the NMR spectroscopic insights gained should prove useful in future structural determination endeavors.",10.1021/ja100742b,2010-05-05,0.579076575931212
Organic Letters,Synthesis of Spirocarbamate Oxindoles via Intramolecular Trapping of a β-Silyl Carbocation by an <i>N</i>-Boc Group,"We report the Lewis acid catalyzed additions of allylsilanes to N-Boc-iminooxindoles and the formation of novel silicon-containing spirocarbamates via intramolecular trapping of a β-silyl carbocation by an N-Boc group. Several transformations display the synthetic utility of these spirocarbamate oxindoles, including a reductive cyclization to access new silylated furoindoline derivatives.",10.1021/ol4010867,2013-06-12,0.5790740960413834
Angewandte Chemie International Edition,Total Synthesis of the Complete Protective Antigen of <i>Vibrio cholerae</i> O139,"The first chemical synthesis of the complete protective O-antigen of a human-disease-causing pathogenic bacterium is described. The synthesis involved a protecting-group strategy that facilitated the regioselectivity of the key transformations, stereoselective glycosylation reactions, and enabled the one-step global deprotection of the completely assembled, fully protected, phosphorylated hexasaccharide by hydrogenation/hydrogenolysis. The final amino-group-functionalized, linker-equipped antigen was obtained in a form ready for conjugation to suitable carriers, for example, proteins, to yield immunogens.",10.1002/anie.201606116,2016-09-14,0.5790736084734102
Organic Process Research & Development,Process Research and Impurity Control Strategy of Esketamine,"An improved synthesis of ( S )-ketamine (esketamine) has been developed, which was cost-effective, and the undesired isomer could be recovered by racemization. Critical process parameters of each step were identified as well as the process-related impurities. The formation mechanisms and control strategies of most impurities were first discussed. Moreover, the ( S )-ketamine tartrate is a dihydrate, which was disclosed for the first time. The practicable racemization catalyzed by aluminum chloride was carried out in quantitative yield with 99% purity. The ICH-grade quality ( S )-ketamine hydrochloride was obtained in 51.1% overall yield (14.0% without racemization) by chiral resolution with three times recycling of the mother liquors. The robust process of esketamine could be industrially scalable.",10.1021/acs.oprd.9b00553,2020-03-18,0.5790714520361298
Angewandte Chemie International Edition,A Desymmetrization‐Based Total Synthesis of Reserpine,"Reported herein is a desymmetrization-based synthetic approach to the fused polycyclic indole alkaloid reserpine. The centerpiece of the developed strategy features an internal desymmetrization process that enabled the use of a readily accessible and nonstereogenic reserpine E-ring precursor, in contrast to the synthesis-intensive and stereodefined E-ring intermediates employed in all past reserpine syntheses. Utilization of inexpensive reagents through an orchestrated sequence of carefully selected chemical transformations further highlight the overall effectiveness of the developed pathway.",10.1002/anie.201810974,2018-11-08,0.5790697084193441
Angewandte Chemie International Edition,"Isolation and Characterization of Pre‐rapamycin, the First Macrocyclic Intermediate in the Biosynthesis of the Immunosuppressant Rapamycin by <i>S. hygroscopicus</i>","It's a rap: A double recombination strategy has been utilized to uncover the biosynthetic route to the key intermediate in the formation of rapamycin. Removal of a section of the rapamycin gene cluster from Streptomyces hygroscopicus produced a strain that generated no rapamycin. Gene complementation proved, surprisingly, that the accumulation of this previously elusive intermediate pre-rapamycin (1) depended on the presence of the gene rapK.",10.1002/anie.200453764,2004-04-02,0.5790685486078299
Synlett,Synthesis of 1-Stannylated and 1-Iodinated 1-Chloroalkenes as Versatile Synthetic Intermediates,"An efficient and convenient synthesis of 1-stannylated and iodinated 1-chloroalkenes is described based on MoBI3-catalyzed hydrostannations of 1-chloroalkynes, followed by a tin-­iodine exchange. The 1-chloro-1-iodoalkenes are suitable substrates for further modification, for example, via cross-coupling reactions.",10.1055/s-0030-1259057,2010-11-19,0.5790681510147687
Journal of the American Chemical Society,Total Synthesis of the Nominal Structure of (+)-Talaromyolide D,"High Resolution Image Download MS PowerPoint Slide We describe a convergent and stereoselective total synthesis of the nominal structure of (+)-talaromyolide D ( 4 ), a recently isolated secondary metabolite. This meroterpenoid features a unique pentacyclic skeleton distinguished by a fused 6/6/6 dihydroisocoumarin core and an unusual pendant dimethylcyclobutanol embedded within a sequence of four contiguous stereocenters. Our synthetic strategy was enabled by a stereoretentive, nickel-catalyzed electrochemical sp 2 –sp 3 decarboxylative cross-coupling, a two-fold bidirectional stitching sequence comprised of an oxime-directed β-C(sp 3 )–H arylation and S N Ar to establish the central ring system of the target as well as a series of two late-stage carboxylic-acid-directed C(sp 2 )–H oxidation reactions to ultimately access the isocoumarin lactone substructure. This asymmetric synthesis provides the first access to the reported structure of talaromyolide D ( 4 ). Comparison of the spectral data showed that the structure of this natural product had been misassigned, and our strategy may present an opportunity for further structural elucidation of the talaromyolide family isolates.",10.1021/jacs.5c10325,2025-08-14,0.5790652568534485
Organic Letters,An Expedient Route to the Calabar Bean Alkaloids (−)-Physovenine and (−)-Physostigmine,An expedient route to the Calabar bean alkaloids (-)-physovenine and (-)-physostigmine has been devised using a chiral building block which was originally designed for diastereocontrolled construction of aldohexoses.,10.1021/ol006065o,2000-08-09,0.5790638185421964
Organic Letters,Ag(I)-Catalyzed Tandem Cyclization–Cycloaddition–Isomerization Reaction of 2-Alkynylbenzaldoxime with Bicyclobutane: A Route to Multiply Substituted Cyclobutanols,"Multiply substituted cyclobutanols are pivotal synthetic intermediates for constructing complex molecular architectures via ring-opening strategies. The development of efficient synthetic methods for these valuable building blocks has garnered significant interest in the chemical community. In this work, we have described a novel silver(I)-catalyzed tandem cyclization-cycloaddition-isomerization sequence with bicyclobutanes and 2-alkynylbenzaldoximes, which offered an effective route to multiply substituted cyclobutanols. This protocol features mild conditions, remarkable stereospecificity, a broad substrate scope, and excellent functional group tolerance. In addition, application potential of this reaction was readily proven by its high efficiency in reactants bearing biological moieties and scale-up experiments.",10.1021/acs.orglett.5c00755,2025-04-01,0.5790627687891905
Organic Letters,Total Synthesis of (+)-<i>ent</i>-Cyclizidine: Absolute Configurational Confirmation of Antibiotic M146791,"The first total synthesis of the enantiomer of the indolizidine alkaloid, cyclizidine, was accomplished from readily available d-serine as the starting chiron. The relevant key reactions involve the stereocontrolled construction of the indolizidine ring system with the required functionality and further elaboration to install the cyclopropyl dienyl side chain. With this total synthesis, the absolute configuration of the natural product based on a redetermination of its X-ray structure has been confirmed.",10.1021/ol103094j,2011-01-27,0.5790527533019341
European Journal of Organic Chemistry,Synthesis and Utility of 2‐Halo‐<i>O</i><sup>6</sup>‐(benzotriazol‐1‐yl)‐Functionalized Purine Nucleosides,"Abstract An efficient synthesis of 2‐halo‐ O 6 ‐(benzotriazol‐1‐yl)‐substituted purine nucleosides has been accomplished via (benzotriazol‐1‐yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (BOP)‐mediated coupling and subsequent halogenation via diazotization of the 2‐amino group of various protected guanosines and directly from guanosine itself. These products are amenable to substitution and coupling reactions in the 2‐ and 6‐positions and, accordingly, provide efficient access to highly functionalized purine nucleosides.",10.1002/ejoc.201001395,2010-12-27,0.5790508998707247
Journal of Organic Chemistry,Synthesis of Macrolactone Core of <i>ent</i>-Formosalide A via Regioselective Ether Cyclization,"Formosalide A is a cytotoxic macrolide isolated from the dinoflagellate Prorocentrum sp, whose structure is characterized by functionalized 5- and 6-membered ether rings embedded in the macrolactone and an all cis -tetraene side chain. Here, we report the synthesis of the macrolactone core of ent -formosalide A. Our approach is highlighted by the Au-mediated 6- exo - dig cyclization for the synthesis of the 6-membered ether ring, which proceeded in a highly regioselective manner. Control experiments demonstrated that the acyclic protecting group of the C9,C10-diol was crucial for the desired 6- exo - dig cyclization. Theoretical studies were performed focusing on structural component analysis, which suggested that the C8–C9–C10-C11 dihedral angle induced by the protecting group controlled the regioselectivity. An additional 6 steps including Shiina macrolactone formation from the 6-membered ether ring completed the synthesis of the macrolactone core of ent -formosalide A.",10.1021/acs.joc.4c00633,2024-05-07,0.5790496574717279
Journal of Organic Chemistry,Enantioselective Approach to Polycyclic Polyprenylated Acylphloroglucinols via Catalytic Asymmetric Intramolecular Cyclopropanation,"The formal enantioselective total synthesis of nemorosone, garsubellin A, clusianone, and hyperforin is described. The catalytic asymmetric intramolecular cyclopropanation (CAIMCP) of an α-diazo ketone, a common synthetic intermediate for the above four polycyclic polyprenylated acylphloroglucinols previously reported by us, exhibited low enantioselectivity. However, CAIMCP of the corresponding α-diazo β-keto sulfone afforded the desired product in 79% yield with 84% ee. Investigation of the CAIMCP of the α-diazo β-keto sulfone demonstrated the formation of a rearrangement product in the presence of molecular sieves 4 Å, whereas, in the presence of H2O, the byproduct derived from ring-opening of the desired cyclopropane was observed. X-ray crystallographic analysis suggested that the above two products are derived from the same chiral intermediate. The product derived from ring-opening of the cyclopropane was successfully transformed to the respective synthetic intermediates for the total syntheses of nemorosone, garsubellin A, clusianone, and hyperforin, which had previously been reported by us.",10.1021/jo5026699,2015-01-12,0.5790493031438194
Synlett,Formal Synthesis of Cytostatin by a Convergent Approach,"A formal synthesis of cytostatin, an antitumor agent, has been achieved according to a convergent approach involving the coupling of a functionalized organolithium (C1-C8 subunit) with an aldehyde (C9-C13 subunit).",10.1055/s-2007-970786,2007-03-26,0.579049138977894
Journal of the American Chemical Society,Total Synthesis of Thiostrepton. Retrosynthetic Analysis and Construction of Key Building Blocks,"The first phase of the total synthesis of thiostrepton (1), a highly complex thiopeptide antibiotic, is described. After a brief introduction to the target molecule and its structural motifs, it is shown that retrosynthetic analysis of thiostrepton reveals compounds 23, 24, 26, 28, and 29 as potential key building blocks for the projected total synthesis. Concise and stereoselective constructions of all these intermediates are then described. The synthesis of the dehydropiperidine core 28 was based on a biosynthetically inspired aza-Diels-Alder dimerization of an appropriate azadiene system, an approach that was initially plagued with several problems which were, however, resolved satisfactorily by systematic investigations. The quinaldic acid fragment 24 and the thiazoline-thiazole segment 26 were synthesized by a series of reactions that included asymmetric and other stereoselective processes. The dehydroalanine tail precursor 23 and the alanine equivalent 29 were also prepared from the appropriate amino acids. Finally, a method was developed for the direct coupling of the labile dehydropiperidine key building block 28 to the more advanced and stable peptide intermediate 27 through capture with the highly reactive alanine equivalent 67 under conditions that avoided the initially encountered destructive ring contraction process.",10.1021/ja0529337,2005-07-19,0.5790473090626692
Synthesis,"A Synthetic Route to Hexahydro[1,4]oxazino[2,3-<i>h</i>] and [3,2-<i>j</i>]β-Carboline Derivatives","Convenient methods for the regioselective formylation of tetrahydro[1,4]oxazino[2,3-f] and [3,2-g]indole derivatives 3 and 4 are described. The obtained formyl derivatives 6 and 8 were further transformed in four steps into the unknown hexahydro[1,4]oxazino[2,3-h] 1 and [3,2-j]β-carbolines 2.",10.1055/s-2002-33909,2002-09-09,0.5790442033146919
Journal of Organic Chemistry,Efficient Method for the Preparation of Peracetylated Neu5Ac2en by Flash Vacuum Pyrolysis,"Peracetylated Neu5Ac2en methyl ester, an intermediate in the synthesis of the influenza neuraminidase inhibitor Relenza, has been synthesized in high yields from peracetylated Neu5Ac methyl ester by flash vacuum pyrolysis. Mechanistic evidence including deuterium labeled studies and DFT (B3LYP) calculations suggest this transformation proceeds via an intramolecular syn-elimination.",10.1021/jo900224t,2009-05-04,0.5790346450773542
Synthesis,Expedient Synthesis of Symmetric Aryl Ketones and of Ambient-Temperature Molten Salts of Imidazole,"All articles of this category A short procedure for the synthesis of 2,2-di(3-thienyl)-1,3-dioxolan is described. The route developed is convenient (only two synthetic and one chromatographic steps are required) and efficient (66% overall yield from 3-bromothiophene). This compound was transformed into the ketone, cyclopenta[2,1- b :3′,4′- b ′]dithiophen-4-one by a known process. Optimized syntheses of symmetric aryl ketones, 1-alkyl-3-methylimidazolium and 1-alkyl-2-methyl-3-methylimidazolium liquid salts are also reported. ketones - thiophenes - imidazoles - heterocycles - sulfonamides",10.1055/s-2000-6416,2000-01-01,0.5790317943334281
European Journal of Organic Chemistry,Synthesis of Phosphonobenzocarbacephems by Intramolecular Radical Cyclization of Haloaryl‐Substituted β‐Lactams,"Abstract A series of benzo‐fused tricyclic β‐lactams, most of them phosphonobenzocarbacephems, were prepared in a straightforward way starting from phosphonoazadienes. In this paper, the synthetic route including a Staudinger reaction towards the β‐lactams, followed by radical ring closing with tributyltin hydride and AIBN, which resulted in the envisaged tricyclic compounds, is reported.",10.1002/ejoc.200901351,2010-01-26,0.5790297630228551
Journal of the American Chemical Society,A de Novo Enantioselective Total Synthesis of (−)-Laulimalide,An enantioselective total synthesis of the naturally occurring anticancer agent (-)-laulimalide is described. The synthesis is characterized by extensive use of new reaction methodologies based on catalytic asymmetric acyl halide-aldehyde cyclocondensation (AAC) reactions and transformations of the derived enantioenriched beta-lactones. The synthesis also incorporates a unique allenylstannane glycal acetate alkylation and chemoselective ring-closing metathesis reaction.,10.1021/ja028019k,2002-10-26,0.579028345914947
Synlett,An Efficient Selective Reduction of Aromatic Azides to Amines Employing BF<sub>3</sub>·OEt<sub>2</sub>/NaI: Synthesis of Pyrrolobenzodiazepines,A selective and facile method for the reduction of aromatic azides to amines by employing borontrifluoride diethyl etherate and sodium iodide. This methodology has been applied towards the preparation of biologically important imine-containing pyrrolobenzodiazepines and their dilactams through intramolecular reductive-cyclization process. In this protocol the reagent systems are amenable for the generation of solution-phase combinatorial synthesis.,10.1055/s-2008-1072742,2008-05-01,0.5790159437204451
Organic Letters,Total Synthesis of Aquatolide,"A total synthesis of the sesquiterpene lactone aquatolide has been accomplished. The central step is an intramolecular [2 + 2]-photocycloaddition of an allene onto an α,β-unsaturated δ-lactone. Other key steps are an intramolecular Horner-Wadsworth-Emmons reaction to close the lactone and an intramolecular Mukaiyama-type aldol reaction to cyclize the eight-membered ring. Racemic aquatolide has been resolved using preparative HPLC.",10.1021/acs.orglett.5b01888,2015-07-17,0.5790157683116741
Synthesis,"Selective Chlorination of Aminoquinones. Synthesis of 2-Amino-3-chloro-1,4-benzoquinones",,10.1055/s-1973-22133,2002-09-12,0.5790068426790628
Synthesis,"A Facile Synthesis of 1,2,3,4-Tetrahydroisoquinolines Through Cyclization of<i>O,N</i>-Acetals","All articles of this category A mild and efficient method for the synthesis of 1,2,3, 4-tetrahydroisoquinolines by a modified Pictet-Spengler reaction involving Lewis acid-mediated cyclization of O,N -acetals is described.",10.1055/s-1987-28089,1987-01-01,0.5790060883269416
Synlett,Enantioselective Preparation of Functionalized Cyclopentanes Using Lewis Acid Mediated Cyclization of Epoxy Allylsilanes: Enantiocontrolled Total Synthesis of (+)-Brefeldin A,"All articles of this category Tin(IV) chloride mediated cyclization of epoxy allylsilanes 2a-c [(2 R ,3 R )-2,3-epoxy-9-trimethylsilyl-7-nonen-1-ols] bearing alkoxy functionalities has been examined establishing an efficient method for the preparation of functionalized chiral cyclopentanes and cyclopentanones. This methodology was utilized in the enantiocontrolled synthesis of (+)-brefeldin A (1,6,7,8,9,11a, 12,13,14,14a-decahydro-1,13-dihydroxy-6-methyl-4 H -cyclopent[f]-oxacyclotridecin-4-one) from ( R )-(-)-epichlorohydrin.",10.1055/s-1990-21213,1990-01-01,0.5790060313615637
Synlett,Synthetic Study of Matrine-Type Alkaloids: Stereoselective Construction of the AB Rings of the Quinolizidine Skeleton,A new method has been developed for the stereoselective construction of the AB rings of the quinolizidine skeleton of ­matrine-type alkaloids with a cis - cis stereochemistry. The key features of this method involve: (i) construction of the quinolizidine by reduction of an acylpyridinium cation; and (ii) late-stage introduction of methoxypyridine by sequential Stille coupling and diastereo­selective hydrogenation reactions.,10.1055/s-0033-1340179,2014-02-10,0.5790056113145962
Organic Letters,Catalytic Asymmetric Assembly of C3-Monosubstituted Chiral Carbazolones and Concise Formal Synthesis of (−)-Aspidofractinine: Application of Enantioselective Pd-Catalyzed Decarboxylative Protonation of Carbazolones,"The first method for the asymmetric synthesis of C3-monosubstituted chiral carbazolones, structural motifs common in medicinal chemistry, has been achieved using Pd-catalyzed decarboxylative protonation of carbazolones. This methodology has been applied to the first catalytic enantioselective formal synthesis of (-)-aspidofractinine with step economy and simplicity.",10.1021/ol501877x,2014-07-25,0.5789933667355153
Synlett,Synthesis of a Cyclopropane Ring Fluorinated Pyrethroid Derivative,All articles of this category Deltamethrin - Fluorinated Intermediates - Pyrethrin,10.1055/s-1996-5715,1996-12-01,0.5789882462355717
Journal of Organic Chemistry,"Predictive Bioinformatic Assignment of Methyl-Bearing Stereocenters, Total Synthesis, and an Additional Molecular Target of Ajudazol B","Full details on the evaluation and application of an easily feasible and generally useful method for configurational assignments of isolated methyl-bearing stereocenters are reported. The analytical tool relies on a bioinformatic gene cluster analysis and utilizes a predictive enoylreductase alignment, and its feasibility was demonstrated by the full stereochemical determination of the ajudazols, highly potent inhibitors of the mitochondrial respiratory chain. Furthermore, a full account of our strategies and tactics that culminated in the total synthesis of ajudazol B, the most potent and least abundant of these structurally unique class of myxobacterial natural products, is presented. Key features include an application of an asymmetric ortholithiation strategy for synthesis of the characteristic anti-configured hydroxyisochromanone core bearing three contiguous stereocenters, a modular oxazole formation, a flexible cross-metathesis approach for terminal allyl amide synthesis, and a late-stage Z,Z-selective Suzuki coupling. This total synthesis unambiguously proves the correct stereochemistry, which was further corroborated by comparison with reisolated natural material. Finally, 5-lipoxygenase was discovered as an additional molecular target of ajudazol B. Activities against this clinically validated key enzyme of the biosynthesis of proinflammatory leukotrienes were in the range of the approved drug zileuton, which further underlines the biological importance of this unique natural product.",10.1021/acs.joc.5b02844,2016-01-21,0.5789843697706426
Tetrahedron,FeCl3-catalyzed efficient synthesis of di(5-methylfuran/thiophen-2-yl)isatin analogues,,10.1016/j.tetlet.2014.05.126,2014-06-23,0.578975337010318
Organic Letters,Asymmetric Total Synthesis of Leptosphin C,"High Resolution Image Download MS PowerPoint Slide A concise enantioselective total synthesis of leptosphine C ( 1 ) has been achieved. Our synthetic strategy features an unprecedented diastereo-/enantioselective Hajos–Parrish–Eder–Sauer–Wiechert (HPESW) reaction for construction of the AB ring system with continuous stereogenic centers (76% yield, 90% ee, dr = 19:1) and an uncommon Pauson–Khand (PK) reaction of geminal dimethyl alkenyl side chains for establishing the CD ring system with the quaternary carbon at C14.",10.1021/acs.orglett.5c03236,2025-08-26,0.578974081676423
Synlett,An Expedient Route to 3-Methoxy-2-furaldehyde,,10.1055/s-0031-1290103,2011-12-09,0.5789739783178414
Synlett,Cumyl: A Better N-Protecting Group of α-Diazo Acetamides for Intramolecular C-H Insertion Reaction and its Application in the Synthesis of Pregabalin and 3-Benzyloxy Pyrrolidine,"Via intramolecular C-H insertion of N-cumyl α-diazo ­acetamides, γ-lactams were efficiently synthesized with excellent regioselectivity. A concise route for the preparation of pregabalin (79% overall yield) and 3-benzyloxy pyrrolidine (21% overall yield) were reported.",10.1055/s-2004-829568,2004-01-01,0.5789738230915686
Tetrahedron,"Asymmetric synthesis via acetal templates. 12. Highly diastereoselective coupling reactions with a ketene acetal. An efficient, asymmetric synthesis of R-(+)-α-lipoic acid",,10.1016/s0040-4039(00)98830-0,1985-01-01,0.578973714931097
Organic Letters,Asymmetric Synthesis of Unnatural (−)-Gracilamine,"-nosyl-tyrosine methyl ester in 10 steps. A tyrosine-derived oxazolidine functions as both a protecting group and a chiral auxiliary to guide an early oxidative dearomatization process that establishes a crucial quaternary carbon and the desymmetrization of a prochiral dienone. The synthesis is completed by a cascade involving a Fukuyama nosyl deprotection/1,4-addition, an azomethine ylide cycloaddition, an oxidative fragmentation, and a double reductive amination. This synthesis highlights the importance of environmentally benign hypervalent iodine reagents as powerful tools in the synthesis of complex structures.",10.1021/acs.orglett.5c02377,2025-07-01,0.5789691647865689
Tetrahedron,A new process of multicomponent Povarov reaction–aerobic dehydrogenation: synthesis of polysubstituted quinolines,,10.1016/j.tetlet.2009.09.125,2009-09-27,0.5789676426007615
Tetrahedron,"Synthesis of 1,3-alternate calix[4]-cyclen-benzo-crown-6 as a hard–soft receptor",,10.1016/s0040-4039(00)01641-5,2000-11-01,0.5789671669048001
Organic Letters,Substituent-Guided Palladium-Ene Reaction for the Synthesis of Carbazoles and Cyclopenta[<i>b</i>]indoles,"An efficient palladium-catalyzed intramolecular Trost-Oppolzer type Alder-ene strategy was developed for the synthesis of carbazoles and cyclopenta[ b]indoles from easily accessible(3-allyl-1 H-indol-2-yl)methyl acetates. This strategy was extended for the synthesis of naphthalenes and dibenzobenzofurans as well. In addition, a short synthesis of antibacterial and antifungal natural product glycozoline and its analogues was also achieved.",10.1021/acs.orglett.9b00410,2019-04-15,0.578963703050534
Organic Process Research & Development,Asymmetric Synthesis of Letermovir Using a Novel Phase-Transfer-Catalyzed Aza-Michael Reaction,"High Resolution Image Download MS PowerPoint Slide The development of a concise asymmetric synthesis of the antiviral development candidate letermovir is reported, proceeding in >60% yield over a total of seven steps from commercially available materials. Key to the effectiveness of this process is a novel cinchonidine-based PTC-catalyzed aza-Michael reaction to configure the single stereocenter.",10.1021/acs.oprd.6b00076,2016-05-13,0.578963565462309
Tetrahedron,An efficient synthesis of 25-hydroxycholesterol from stigmasterol,,10.1016/s0040-4039(01)93251-4,1977-01-01,0.578956660181539
Journal of Organic Chemistry,A Modular and Concise Total Synthesis of (±)-Daurichromenic Acid and Analogues,"A modular and concise total synthesis of (+/-)-daurichromenic acid has been accomplished in four steps from ethyl acetoacetate, ethyl crotonate, and trans,trans-farnesal. A series of analogues of this natural product, which has potent anti-HIV activity, were also prepared from ethyl or methyl acetoacetate and a series of readily available alpha,beta-unsaturated esters and aldehydes.",10.1021/jo049703f,2004-04-24,0.5789518423020484
Organic Letters,An Approach to the Hexacyclic Skeleton of Trigonoliimines,"A strategy to construct the hexacyclic skeleton of trigonoliimines A, B and their derivatives involving a carbanion-triggered intramolecular cyclization of a seven-membered ring and a subsequent six-membered ring formation in one pot is described.",10.1021/ol202475r,2011-10-11,0.5789504465907173
Journal of Organic Chemistry,"Three-Step Synthesis of Ethyl Canthinone-3-carboxylates from Ethyl 4-Bromo-6-methoxy-1,5-naphthyridine-3-carboxylate via a Pd-Catalyzed Suzuki–Miyaura Coupling and a Cu-Catalyzed Amidation Reaction","Ethyl canthin-6-one-1-carboxylate (1b) and nine analogues 1c-k were prepared from readily prepared ethyl 4-bromo-6-methoxy-1,5-naphthyridine-3-carboxylate (2b) via a three-step non-classical approach that focused on construction of the central pyrrole (ring B) using Pd-catalyzed Suzuki-Miyaura coupling followed by Cu-catalyzed C-N coupling. Furthermore, treatment of the ethyl canthinone-1-carboxylate 1b with NaOH in DCM/MeOH (9:1) gave the canthin-6-one-1-carboxylic acid (6) in high yield. All compounds are fully characterized.",10.1021/jo200824b,2011-05-12,0.5789478642557294
Angewandte Chemie International Edition,Asymmetric Synthesis of Bryostatin 2,The potent bryostatin antitumor agents are currently in phase II clinical trials for the treatment of a variety of forms of cancer. Aldol reactions and directed reductions are among the essential steps for the formation of fragments A-C in the total synthesis of the title compound. Coupling of these fragments by sulfone-based olefination and alkylation reactions was followed by macrocyclization and introduction of the enoate moieties on rings B and C.,10.1002/(sici)1521-3773(19980918)37:17<2354::aid-anie2354>3.0.co;2-9,1998-09-18,0.5789466190182424
Angewandte Chemie International Edition,Asymmetric Synthesis of Bryostatin 2,The potent bryostatin antitumor agents are currently in phase II clinical trials for the treatment of a variety of forms of cancer. Aldol reactions and directed reductions are among the essential steps for the formation of fragments A–C in the total synthesis of the title compound. Coupling of these fragments by sulfone-based olefination and alkylation reactions was followed by macrocyclization and introduction of the enoate moieties on rings B and C.,10.1002/(sici)1521-3773(19980918)37:17<2354::aid-anie2354>3.3.co;2-0,1998-09-18,0.5789466190182424
Angewandte Chemie International Edition,Cover Picture: Short Chemoenzymatic Total Synthesis of <i>ent</i>‐Hydromorphone: An Oxidative Dearomatization/Intramolecular [4+2] Cycloaddition/Amination Sequence (Angew. Chem. Int. Ed. 17/2014),"A 12-step chemoenzymatic total synthesisof ent-hydromorphone from β-bromoethylbenzene is described by T. Hudlicky and V. Varghese in their Communication on page 4355 ff. The key steps consist of enzymatic dihydroxylation, Mitsunobu coupling, and oxidative dearomatization followed by intramolecular [4+2] cycloaddition. This approach holds potential for further optimization of morphine alkaloid syntheses. We acknowledge the legendary efforts of the chemists pictured, who dedicated their careers to the chemistry of morphine. Cover design: Dennis Ceci, Tomas Hudlicky, Jordan Froese (Brock University).",10.1002/anie.201401117,2014-03-25,0.5789449506487635
European Journal of Organic Chemistry,Access to Pyrrolocoumarins through DBU‐Mediated Coupling of 2‐Oxo‐2<i>H</i>‐chromene‐3‐carbaldehydes and Phenacyl Azides,"Abstract 1,8‐Diazabicyclo [5.4.0]undec‐7‐ene (DBU) mediated annulation of 4‐(benzylthio/arylthio)‐2‐oxo‐2 H ‐chromene‐3‐carbaldehydes with phenacyl azides for the synthesis of biologically relevant pyrrolocoumarins was developed. This operationally simple and unique synthetic strategy allows the formation of desired pyrrolocoumarin in good yields (67‐84 %), and generates a new C−C and C−N bond in the overall process.",10.1002/ejoc.202101237,2021-12-15,0.5789401046124183
Tetrahedron,"Silver(I) catalyzed amino cyclization of O-(2,3-butadienyl) carbamates: an efficient and stereoselective synthesis of 4-vinyl-2-oxazolidinones",,10.1016/0040-4039(91)80169-7,1991-10-01,0.5789374197643766
Journal of Organic Chemistry,Gold(III)-Catalyzed Selective Cyclization of Alkynyl Quinazolinone-Tethered Pyrroles: Synthesis of Fused Quinazolinone Scaffolds,"A series of 1,2- and 2,3-fused quinazolinones have been synthesized in good to excellent yields through gold-catalyzed selective hydroarylations of alkynyl quinazolinone-tethered pyrroles. The studies revealed that 1,2-fused quinazolinones were obtained through a 1,3-rearrangement and sequential 6- exo-trig cyclization of N1-alkynyl quinazolinone-tethered pyrroles, while N3-alkynyl quinazolinone-tethered pyrroles went through 6- exo-dig or 7- endo-dig cyclizations directly to afford 2,3-fused quinazolinones. The fused quinazolinones could be prepared at gram scale in three steps from commercial ortho-aminobenzamide.",10.1021/acs.joc.8b00168,2018-05-17,0.5789346211350395
Tetrahedron,Regioselective synthesis of hydroxy butenolides : A convenient synthesis of A-factor,,10.1016/s0040-4039(00)73253-9,1994-05-01,0.5789332246329321
European Journal of Organic Chemistry,An Efficient Synthesis of 5-(or 6-)Arylbenzoindolizidine and -quinolizidine Derivatives,"A new methodology for the synthesis of (hetero)arylated benzoindolizidine and benzoquinolizidine derivatives through sequential reduction of pyrrolidine- and piperidine-based aromatic enamides, and ultimate cyclization, is reported.",10.1002/(sici)1099-0690(199909)1999:9<2345::aid-ejoc2345>3.0.co;2-p,1999-09-01,0.5789331507313695
Tetrahedron,"New nonsolidphase method for quick, quantitative synthesis of analytically pure peptides without intermediate or final purifications: I. synthesis of a nonapeptide",,10.1016/s0040-4039(01)97848-7,1970-01-01,0.5789222363186649
Organic Process Research & Development,Quaternary Chiral Center <i>via</i> Diastereoselective Enolate Amination Enables the Synthesis of an Anti-inflammatory Agent,"The d -leucine amino acid residue necessary for the synthesis of BMS-561392, 1, was employed as a chiral directing group for a diastereoselective enolate amination to establish the quaternary chiral center. Enhanced diastereomeric ratios were observed while conducting the enolate amination with 1-chloro-1-nitrosocyclopentane 6 in the presence of LiCl. Analogies are drawn between known tertiary amide amino alcohol chiral auxiliaries which have been used to effect diastereoselective enolate alkylations and aminations. Once the stereochemical features of 1 were established, an efficient reaction sequence was devised to complete its synthesis. During the course of this research, accelerated reaction calorimetry (ARC) data substantiated that the aminating agent 1-chloro-1-nitrosocyclopentane 6 was not safe to use as a neat compound. Consequently, a preparation and use of 6 as a stock solution in methyl tert -butyl ether (MTBE) was developed that rendered it safe for use.",10.1021/op900255k,2009-12-03,0.5789214149738366
Synlett,Synthetic Studies on Bengazoles of Marine Sponge Origin. Synthesis of the Core Bis-oxazole Fragments,"(opens in new window) Buy Article (opens in new window) Permissions and Reprints (opens in new window) All articles of this category (opens in new window) The core bis-oxazole fragment 3 was constructed by the coupling of the aldehyde ( 6 ) with the lithiated oxazoles ( 7 ), oxidation of the resulting bis-oxazolyl methanol ( 11 ), followed by the asymmetric reduction with ( R )-(+)-BINAL-H as key steps. Preparation of another bis-oxazole fragment ( 4 ) was accomplished by the Barton-McCombie radical deoxygenation reaction of 11 . oxazoles - bis-oxazoles - bengazoles - stereoselective reduction - deoxygenation",10.1055/s-1998-1852,1998-09-01,0.5789183822977909
Tetrahedron,"A new synthetic method for an acromelic acid analog, a potent neuroexcitatory kainoid amino acid, via photoinduced benzyl radical cyclization",,10.1016/s0040-4039(02)01817-8,2002-10-01,0.5789141926757854
Synlett,Efficient One-Pot Synthesis of 2-Substituted Benzimidazoles from Triacyloxyborane Intermediates,An efficient one-pot synthesis of 2-substituted benzim­idazoles via triacyloxyborane intermediates is reported. The mild protocol is efficient and tolerant of acid-labile functional groups.,10.1055/s-0031-1290129,2012-01-01,0.578913458856403
Synthesis,"Intramolecular Diels–Alder and [3+2] Cycloaddition Reactions in the One-Pot Synthesis of Epoxypyrrolo[3,4-g]indazoles","A one-pot approach for the synthesis of epoxypyrrolo[3,4-g]indazoles is presented. The first step was initiated by a three-component reaction of an isocyanide, a dialkyl acetylenedicarboxylate, and 2-furancarboxylic acid, and led to 1,3-dioxoepoxyisoindole, followed by the addition of hydrazonoyl chloride through a [3+2]-cycloaddition reaction in the second step. The key step in the formation of final compound involves a bicyclization strategy through intramolecular Diels–Alder­ (IMDA) reaction.",10.1055/s-0037-1612426,2019-04-10,0.5789067686725734
Synlett,Friedel–Crafts Cyclodehydration Approach toward the Synthesis of Ellipti-cine and 9-Methoxyellipticine,"An expedient synthesis of biologically important pyrido[4,3- b ]carbazole alkaloids, ellipticine and 9-methoxyellipticine, is reported. Our synthetic approach applies a key H 3 PO 4 -mediated Friedel–Crafts cyclodehydration to construct the pyridine core.",10.1055/s-0034-1379305,2014-10-20,0.5789049556760123
Journal of the American Chemical Society,Enantioselective Total Synthesis of (+)-Aberrarone,"We disclose the first total synthesis of (+)-aberrarone, a diterpenoid natural product featuring a 5-5-5-6-fused tetracyclic skeleton. Key to the approach is a Au-catalyzed-Sn-mediated Meyer-Schuster-Nazarov-cyclopropanation-aldol cascade, which closes four rings in high yield. The convergent approach furnishes the natural product (+)-aberrarone stereoselectively in 15 steps. We highlight the benefits of using a Sn-alkoxide to considerably expand the opportunities of Au-catalysis for the synthesis of complex molecules.",10.1021/jacs.2c07150,2022-08-19,0.5789033188576851
Organic Letters,"Synthesis of 5α,6-Dihydroveragranines A and B","The 5α,6-dihydro congeners of veragranines A and B, two steroidal alkaloids with an unprecedented hexacyclic skeleton and potent analgesic effects, were synthesized from hecogenin acetate within six steps. This work enables quick access to the hexacyclic skeleton and is amendable to prepare other D-ring-modified congeners.",10.1021/acs.orglett.2c02367,2022-08-03,0.5789028304746393
Organic Letters,"Total Synthesis of the Sensitive Triyne Natural Product (4<i>S</i>,5<i>S</i>)-4,8-Dihydroxy-3,4-dihydrovernoniyne and All of Its Stereoisomers","An efficient total synthesis of the revised structure of the sensitive triyne natural product, (4 S,5 S )-4,8-dihydroxy-3,4-dihydrovernoniyne, and all of its stereoisomers, that is, the previously proposed (4 S,5 R ), (4 R,5 R ), and (4 R,5 S ), has been accomplished from chiral pool compounds l -mannonic-γ-lactone and d -glucono-δ-lactone. The key features involve a one-pot conversion of the chiral pool compounds into the γ-vinyl-β-hydroxy-γ-lactones, the heteroatom-directed Wacker oxidation, the Seyferth–Gilbert reaction, and Cadiot–Chodkiewicz coupling. The synthesis also involves minimal protecting groups (only tert -butyldimethylsilyl) and is completed in seven to eight steps.",10.1021/acs.orglett.9b01897,2019-07-17,0.5789016505984466
Synthesis,Synthesis and Incorporation into α-DNA of a Novel Conformationally Constrained α-Nucleoside Analogue,"The synthesis and incorporation into α-DNA of a novel conformationally constrained α-nucleoside analogue is described. The carbohydrate part of this analogue was prepared in 4 steps from the known bicyclic precursor 1 via a stereospecific, intramolecular, Et3B-mediated radical addition to a keto function as the key step. The thus obtained intermediate 4 was transformed stereoselectively into the corresponding α-nucleoside analogues 7 and 8 containing the bases adenine and thymine, and were further elaborated into the phosphoramidite building blocks 11 and 12. Both building blocks were incorporated into α-oligodeoxynucleotides and their pairing behavior to parallel complementary DNA was studied by UV-melting experiments. Single substitutions of α-deoxyribnucleoside units by the new analogues in the center of duplexes were found to be thermally destabilizing by only -0.8 to -3.1 °C.",10.1055/s-2002-25755,2002-01-01,0.5788969243852593
Organic Process Research & Development,"Synthesis of 1,5-Bis(triphenylphosphonium)pentan-3-ol Dichloride and Its Application to the Preparation of 1,7-Di(pyridin-3-yl)heptan-4-ol","The preparation of 1,7-di(pyridin-3-yl)-heptan-4-ol ( 1 ), an important intermediate in the synthesis of a series of novel cancer multidrug resistance (CMR) chemosensitizers, has been accomplished in high overall yield via the new bis-Wittig reagent 1,5-bis(triphenylphosphonium)pentan-3-ol dichloride ( 6 ), that can also be used in the preparation of other members of the class of CMRs.",10.1021/op020050j,2002-10-26,0.5788937548424198
European Journal of Organic Chemistry,Three‐Component Multi‐Catalytic Enantioselective Oxa‐Michael/Aldolization Sequence and Application to (+)‐Yashabushitriol Synthesis,"By a selective three‐component multi‐catalytic sequence, amino‐catalyzed oxa‐Michael addition of oximes to α,β‐unsaturated aldehydes has been combined with a copper‐catalyzed decarboxylative aldolization. This one‐pot procedure enables the rapid construction of functionalized ketodiol scaffolds in 85 to 94% ee . Simple reduction of both the resulting oxime and ketone functions delivered the corresponding 1,3,5‐triols of interest in a minimum of steps while considerably limiting waste generation. This methodology has been applied to the shortest (4 steps) synthesis of (+)‐yashabushitriol, highlighting the synthetic potential of this new multi‐catalytic sequence.",10.1002/ejoc.202000185,2020-02-24,0.5788914596741334
European Journal of Organic Chemistry,"Concise Total Synthesis of Hydrazidomycin A, a Rare Hydrazide Metabolite of <i>Streptomyces atratus</i>","Abstract Hydrazidomycins A–C and elaiomycins B–C represent a family of unusual, naturally occurring enehydrazides produced by Streptomyces sp. A general synthetic approach to access these densely functionalized hydrazine derivatives is exemplified by the first total synthesis of hydrazidomycin A. The modular synthesis involves a ruthenium‐catalyzed hydroamidation of an alkyne and a hydrazide‐derived phthalimide to yield predominantly the Z ‐configured enehydrazide.",10.1002/ejoc.201300532,2013-06-06,0.5788839120176089
Tetrahedron,An approach to the stereocontrolled synthesis of polysubstituted chiral butenolides and γ-lactones,,10.1016/s0040-4039(00)71265-2,1991-05-01,0.5788804843546558
European Journal of Organic Chemistry,Flexible Synthesis of Planar Chiral Azoninones and Optically Active Indolizidinones,"Abstract The flexible synthesis of defined substituted optically active indolizidinones starting from chiral pool ( S )‐proline and trans 4‐hydroxy‐( S )‐proline is described. Several defined 2‐vinylpyrrolidines were generated in short sequences. The aza‐Claisen rearrangement using chloro and phenylketene equivalents delivered nine‐membered‐ring lactams with up to three stereogenic centres and pS ‐arranged E olefins. Depending on the substitution pattern, certain azoninones had a flexible conformation and showed pS / pR double‐bond flipping. Treatment of the unsaturated lactams with the soft electrophile iodine induced diastereoselective transannular ring contractions. Here, the planar chiral arrangement of the azoninone double bond predetermined the bridgehead configuration of the product indolizidinones. Thus, the ( S )‐proline starting materials could be used to gain access to either one of the two antipodal series of indolizidinone products. The indolizidinone scaffolds should serve as versatile key intermediates in the synthesis of natural products and pharmaceutically important molecules.",10.1002/ejoc.201402720,2014-08-21,0.578878409466136
Synthesis,Improved Synthesis of the π-Electron Donor Bis(ethylenethio)tetrathiafulvalene (BET-TTF),"All articles of this category Following a three step route, 5,6-dihydrothieno[2,3- d ]-1,3-dithiol-2-one ( 5 ) was synthesized in gram quantities starting from commercially available reagents. Coupling of 5 with trimethyl phosphite gave the π-donor bis(ethylenethio)tetrathiafulvalene 1 in 80% yield. tetrathiafulvalene analog - 1,3-dithiol-2-one - trimethyl phosphite - coupling reactions",10.1055/s-1999-3451,1999-04-01,0.5788755615809255
Angewandte Chemie International Edition,Super‐heptazethrene,"The challenging synthesis of a laterally extended heptazethrene molecule, the super-heptazethrene derivative SHZ-CF3, is reported. This molecule was prepared using a strategy involving a multiple selective intramolecular Friedel-Crafts alkylation followed by oxidative dehydrogenation. Compound SHZ-CF3 exhibits an open-shell singlet diradical ground state with a much larger diradical character compared with the heptazethrene derivatives. An intermediate dibenzo-terrylene SHZ-2H was also obtained during the synthesis. This study provides a new synthetic method to access large-size quinoidal polycyclic hydrocarbons with unique physical properties.",10.1002/anie.201602997,2016-05-30,0.578874619821625
Tetrahedron,Diastereoselective synthesis of the saponaceolide tricyclic spiroketal substructure,,10.1016/s0040-4039(00)77656-8,1993-04-01,0.5788652573314921
Tetrahedron,Diastereoselective synthesis of N-sulfinyl α-aminophosphine sulfides and phosphines,,10.1016/j.tetlet.2017.03.067,2017-03-23,0.5788652573314921
Tetrahedron,Diastereoselective synthesis of deprotectable isoxazolidines,,10.1016/j.tetlet.2013.01.105,2013-02-01,0.5788652573314921
Tetrahedron,"Diastereoselective synthesis of 2,6-Imino-D-allonates from chromium carbene iminosugars",,10.1016/s0040-4039(98)00620-0,1998-05-01,0.5788652573314921
Tetrahedron,A diastereoselective synthesis of (±) trichodiene,,10.1016/s0040-4039(01)80687-0,1989-01-01,0.5788652573314921
Tetrahedron,Enantio- and diastereoselective synthesis of all four stereoisomers of formoterol,,10.1016/s0040-4039(97)00088-9,1997-02-01,0.5788652573314921
Tetrahedron,Regio- and diastereoselective synthesis of bifunctionalized limonenes,,10.1016/j.tetlet.2005.08.009,2005-08-17,0.5788652573314921
Tetrahedron,Diastereoselective synthesis of ribofuranosyl glycines,,10.1016/s0040-4039(00)71250-0,1991-05-01,0.5788652573314921
Tetrahedron,Diastereoselective synthesis of bicyclopropanes,,10.1016/0040-4039(94)88459-5,1994-12-01,0.5788652573314921
Tetrahedron,A diastereoselective synthesis of girolline,,10.1016/0040-4039(91)80346-8,1991-03-01,0.5788652573314921
Tetrahedron,Enantio- and diastereoselective synthesis of erysulfone and erysulfoxide,,10.1016/s0040-4039(97)10440-3,1997-12-01,0.5788652573314921
Tetrahedron,Diastereoselective isothiourea iodocyclization for manzacidin synthesis,,10.1016/s0040-4039(03)00431-3,2003-03-01,0.5788652573314921
Tetrahedron,Diastereoselective synthesis of the top half of kijanolide,,10.1016/s0040-4039(00)70684-8,1989-01-01,0.5788652573314921
Tetrahedron,Diastereoselective synthesis of l-(+)-homolamivudine,,10.1016/s0040-4039(99)01935-8,1999-12-01,0.5788652573314921
Synthesis,"Efficient Synthesis of (2S,12′R)-2-(12′-Aminotridecyl)pyrrolidine: A Defense Alkaloid of the Mexican Bean Beetle","All articles of this category The synthesis of (2 S ,12′ R )-2-(12′-aminotridecyl)pyrrolidine [( S , R )- 8 ], a defense alkaloid of the Mexican bean beetle Epilachna varivestis starting from ( R )-proline is described. The second stereogenic center is generated by nucleophilic 1,2-addition of methyllithium to an aldehyde-SAMP-hydrazone, followed by reductive N-N bond cleavage. The product is obtained in good yield and high enantiomeric and diastereomeric purity. natural products - asymmetric synthesis - alkaloids - nucleophilic 1,2-addition - SAMP/RAMP hydrazone method - pyrrolidines",10.1055/s-2000-6379,2000-01-01,0.5788645786345465
Angewandte Chemie International Edition,Total Synthesis of the Protein Phosphatase 2A Inhibitor Lactodehydrothyrsiferol,"Cascading epoxides: The squalene-derived polyether lactodehydrothyrsiferol (1) has been prepared through a convergent sequence that features an epoxide-opening cascade to construct the tetrahydrofuran and tetrahydropyran subunits. Additional features include a stereodivergent diene diepoxidation, a monodeoxygenation of a triol, and complex fragment couplings through Suzuki and Nozaki–Hiyama–Kishi reactions.",10.1002/anie.201007757,2011-04-21,0.5788627280922215
Tetrahedron,A stereoselective synthesis of the azaspiboundecane ring system of (−)-histrionicotoxin from (+)-glutamic acid,,10.1016/s0040-4039(00)85162-x,1986-01-01,0.5788608782736245
Organic Letters,Biomimetic Approach to Perophoramidine and Communesin via an Intramolecular Cyclopropanation Reaction,"[reaction: see text] Starting from tryptamine 4 and isatin 5, a biomimetic approach to the pentacyclic substructure 1 of perophoramidine and communesin was developed. The key steps were to create a stable three/six bicyclic system 2 on the 2,3-double bond of an indole derivative 3 by an intramolecular cyclopropanation, followed by ring opening of the resulting cyclopropane ring with the in situ generated amine group of an aniline.",10.1021/ol0607138,2006-04-19,0.5788599837385786
Journal of Organic Chemistry,Enantioselective Synthesis of a γ-Secretase Modulator via Vinylogous Dynamic Kinetic Resolution,"Two efficient asymmetric routes to γ-secretase modulator BMS-932481, under investigation for Alzheimer's disease, have been developed. The key step for the first route involves a challenging enantioselective hydrogenation of an unfunctionalized trisubstituted alkene to establish the benzylic stereocenter, representing a very rare case of achieving high selectivity on a complex substrate. The second route demonstrates the first example of a vinylogous dynamic kinetic resolution (VDKR) ketone reduction, where the carbonyl and the racemizable stereocenter are not contiguous, but are conjugated through a pyrimidine ring. Not only did this transformation require both catalyst and substrate control to correctly establish the two stereocenters, but it also necessitated that the nonadjacent benzylic center of the ketone substrate be more acidic than that of the alcohol product to make the process dynamic. DFT computations aided the design of this novel VDKR pathway by reliably predicting the relative acidities of the intermediates involved.",10.1021/acs.joc.8b01734,2018-08-13,0.5788560621655183
Tetrahedron,A facile route to aromatic ring-annelated bis(ethylenedithio)tetrathiafulvalene derivatives,,10.1016/0040-4039(96)01846-1,1996-11-01,0.5788547441544966
Angewandte Chemie International Edition,"Highly Selective Thiiranation of 1,2‐Allenyl Sulfones with Br<sub>2</sub> and Na<sub>2</sub>S<sub>2</sub>O<sub>3</sub>: Mechanism and Asymmetric Synthesis of Alkylidenethiiranes","Axial-to-central chirality transfer is highly efficient in a regioselective synthesis of (1-sulfonyl)alkylidenethiiranes from 1,2-allenyl sulfones (see scheme). A cyclic intermediate formed upon the electrophilic addition of bromine to the allene was isolated and characterized. A mechanism is proposed on the basis of this intermediate and the observed stereoselectivity.",10.1002/anie.200700619,2007-05-02,0.5788496347171777
Journal of the American Chemical Society,Oxetane Synthesis via Alcohol C–H Functionalization,"Oxetanes are strained heterocycles with unique properties that have triggered significant advances in medicinal chemistry. However, their synthesis still presents significant challenges that limit the use of this class of compounds in practical applications. In this Letter, we present a methodology that introduces a new synthetic disconnection to access oxetanes from native alcohol substrates. The generality of the approach is demonstrated by the application in late-stage functionalization chemistry, which is further exploited to develop a single-step synthesis of a known bioactive synthetic steroid derivative that previously required at least four synthetic steps from available precursors.",10.1021/jacs.3c04891,2023-07-18,0.578846898445071
Journal of Organic Chemistry,Direct Synthesis of α-Fluoro-α-Triazol-1-yl Ketones from Sulfoxonium Ylides: A One-Pot Approach,"The work reported herein showcases a new route to access α-fluoro-α-triazol-1-yl ketones from sulfoxonium ylides via α-azido-α-fluoro ketone intermediates. In a one-pot, two-step sequence, the ketosulfoxonium reactant initially undergoes insertion of F + and N 3 –, followed by a subsequent CuAAC reaction with arylacetylenes to install a 1,4-triazolo moiety. The approach allows for modification to both the sulfoxonium ylide and arylacetylene reactants. Fifteen examples have been reported, with yields ranging between 22% and 75%.",10.1021/acs.joc.1c01441,2021-08-23,0.5788350280843323
Angewandte Chemie International Edition,"Asymmetric Total Synthesis of Hasubanan Alkaloids: Periglaucines A–C, <i>N,O</i>‐Dimethyloxostephine and Oxostephabenine","Abstract We report herein the asymmetric total synthesis of periglaucines A–C, N , O ‐dimethyloxostephine and oxostephabenine. The key strategies used include: 1) a Rh I ‐catalyzed regio‐ and diastereoselective Hayashi‐Miyaura reaction to connect two necessary fragments; 2) an intramolecular photoenolization/Diels–Alder (PEDA) reaction to construct the highly functionalized tricyclic core skeleton bearing a quaternary center; 3) a bio‐inspired intramolecular Michael addition and transannular acetalization to generate the aza[4.4.3]propellane and the tetrahydrofuran ring.",10.1002/anie.202214873,2022-11-11,0.5788336924810269
Journal of Organic Chemistry,An Efficient Synthesis of the Constrained Peptidomimetic 2-Oxo-3-(<i>N</i>-9-fluorenyloxy-carbonylamino)-1-azabicyclo[4.3.0]nonane-9-carboxylic Acid from Pyroglutamic Acid,"[reaction: see text] Azabicyclo[X.Y.0]alkane amino acids are rigid dipeptide mimetics that are useful tools for structure-activity studies in peptide-based drug discovery. Herein, we report an efficient synthesis of three diastereomers of 9-tert-butoxycarbonyl-2-oxo-3-(N-tert-butoxycarbonylamino)-1-azabicyclo[4.3.0]nonane (3S,6S,9S, 3S,6R,9R, and 3S,6R,9S). Methyl N-Boc-pyroglutamate is cleaved with vinylmagnesium bromide to produce an acyclic gamma-vinyl ketone. Michael addition of N-diphenylmethyleneglycine tert-butyl ester produces the N-Boc-delta-oxo-alpha,omega-diaminoazelate intermediate, which, on hydrogenloysis, gives the fused ring system. Acidolytic deprotection followed by Fmoc-protection provided building blocks suitable for solid-phase synthesis.",10.1021/jo0515935,2005-10-28,0.5788237256294918
Journal of the American Chemical Society,Asymmetric Synthesis of Methylenetetrahydrofurans by Palladium-Catalyzed [3 + 2] Cycloaddition of Trimethylenemethane with Aldehydes – A Novel Ligand Design,The palladium-catalyzed [3 + 2] cycloaddition of trimethylenemethane (TMM) with aldehydes is a direct and efficient route to methylenetetrahydrofurans. Herein we describe the first asymmetric synthesis of methylenetetrahydrofurans utilizing a palladium-TMM complex in the presence of a novel phosphoramidite ligand possessing a stereogenic phosphorus. The method allows for the formation of chiral disubstituted tetrahydrofurans in good yields and enantioselectivities.,10.1021/ja201181g,2011-04-25,0.5788221402010983
Tetrahedron,Synthesis of 6-aryl/heteroaryl-4-oxo-4 H -chromene-2-carboxylic ethyl ester derivatives,,10.1016/j.tetlet.2016.05.096,2016-05-26,0.5788209239029986
Journal of Organic Chemistry,"An In-Depth Study on Ring-Closing Metathesis of Carbohydrate-Derived α-Alkoxyacrylates:  Efficient Syntheses of DAH, KDO, and 2-Deoxy-β-KDO","Novel, efficient synthetic pathways to DAH, KDO, and 2-deoxy-beta-KDO are described. Ring-closing metathesis (RCM) of highly functionalized alpha-alkoxyacrylate fragments resulted in a series of synthetically versatile oxygen heterocyclic intermediates. Further functionalization of the resulting enol ether double bond and subsequent deprotection provided the natural products in high overall yields, starting from commercially available protected sugars.",10.1021/jo060913x,2006-07-26,0.5788201233538577
European Journal of Organic Chemistry,Stereoselective Domino Semipinacol‐Schmidt Reaction: Diastereoselective Synthesis of 7 a‐<i>epi</i>‐(+)‐Lepadiformine C and Formal Synthesis of 7 a‐<i>epi</i>‐(−)‐Lepadiformine A,"Abstract A concise approach has been developed for the diastereoselective synthesis of the azatricyclic core of (−)‐7 a‐ epi ‐lepadiformine A ( 8 a ) and (−)‐7 a‐ epi ‐lepadiformine C ( 8 b ) using stereoselective domino semipinacol‐Schmidt reaction as a key step. In presence of TiCl 4 , the oxaspiropentane‐azide derivatives underwent stereoselective domino cyclization to furnish the corresponding angularly fused azatricyclic cores in very good yields. Moreover, azatricyclic core of (−)‐7 a‐ epi ‐lepadiformine A has also been realized, in a stepwise manner, through the intramolecular Schmidt reaction of azido‐spirocyclobutanone intermediate. The synthetic utility of domino semipinacol‐Schmidt reaction is further shown in the diastereoselective synthesis of (+)‐7 a‐ epi ‐lepadiformine C ( 7 ).",10.1002/ejoc.202201490,2023-02-26,0.5788201141219516
Tetrahedron,Synthesis of a first-generation l-rhamnose dendron,,10.1016/j.tetlet.2020.151706,2020-02-10,0.5788191720725234
Organic Letters,Chemical Synthesis of a Branched Nonasaccharide Fragment from <i>Helicobacter pylori</i> Lipopolysaccharide,"A chemical synthesis of a unique nanosaccharide fragment from Helicobacter pylori lipopolysaccharide was achieved via a convergent glycosylation method. Challenges involved in the synthesis include the highly stereoselective construction of β-3-deoxy- d - manno -oct-2-ulosonic acid (Kdo) and two 1,2- cis -glycosidic linkages, as well as the formation of a branched 2,7-disubstituted heptose subunit. Hydrogen-bond mediated aglycone delivery strategy and benzoyl-directing remote participation effect were employed, respectively, for the efficient generation of the desired β-Kdo glycoside and 1,2- cis -α- l -fucoside/ d -glucoside. Moreover, the key branched framework was successfully established through a [(7 + 1) + 1] assembly approach involving the stepwise glycosylation of the heptasaccharide alcohol with two monosaccharide donors. The synthesized 1 containing a propylamine linker at the reducing end can be covalently bound to a carrier protein for further immunological studies.",10.1021/acs.orglett.4c00271,2024-03-05,0.5788161632883726
Tetrahedron,"NaIO4-mediated asymmetric bromohydroxylation of α,β-unsaturated carboxamides with high diastereoselectivity: a short route to (−)-cytoxazone and droxidopa",,10.1016/j.tetlet.2006.12.109,2006-12-26,0.5788139237942929
Organic Letters,Ten-Gram-Scale Total Synthesis of the Anticancer Drug Candidate E7130 to Supply Clinical Trials,"E7130 is a novel drug candidate with an exceedingly complex chemical structure of the halichondrin class, discovered by a total synthesis approach through joint research between the Kishi group at Harvard University and Eisai. Only 18 months after completion of the initial milligram-scale synthesis, ten-gram-scale synthesis of E7130 was achieved, providing the first good manufacturing practice (GMP) batch to supply clinical trials. This paper highlights the challenges in developing ten-gram-scale synthesis from the milligram-scale synthesis.",10.1021/acs.orglett.3c03663,2024-01-22,0.5788061257400566
European Journal of Organic Chemistry,First Total Synthesis of <sup>14</sup>C‐Labeled Procyanidin B2 – A Milestone Toward Understanding Cocoa Polyphenol Metabolism (Eur. J. Org. Chem. 36/2008),"Abstract The cover picture shows the key steps of the first asymmetric total synthesis of procyanidin B2, one of the major dietary polyphenols present in cocoa and chocolate. During the last decades, the health benefits of foods consumed for pure pleasure have received much recognition. Many biological studies have evidenced the beneficial health effects of procyanidins. However, the absorption and metabolism of procyanidins is still not fully understood, and some aspects are still controversial. In order to strengthen this knowledge, the first total synthesis of procyanidin B2 was developed and applied to the preparation of a regioselectively radiolabeled analogue incorporating a 14 C label at the 2‐position of the upper C‐ring moiety. This enantioselective synthesis was achieved in 14 “hot” steps, involving as key steps the Sharpless dihydroxylation of an elaborated alkene, a stereoselective intramolecular cyclization and the condensation of two (–)‐epicatechin units. The radiolabelled procyanidin B2 obtained through this reaction pathway will be used in bioavailability studies. Details are discussed in the article by F. Viton et al. on p. 6069 ff. The authors acknowledge Tonic Life Communications for the design of the cover page and the European Union 6th Framework project “FLAVO” for partial support of this research work.",10.1002/ejoc.200890099,2008-12-01,0.5788054972896585
Organic Process Research & Development,An Efficient Process of Racemization of 3-(Carbamoylmethyl)-5-methylhexanoic acid: A Pregabalin Intermediate,"A simple and cost-effective process for racemization of undesired ( S )-3-(carbamoylmethyl)-5-methylhexanoic acid ( 9 ), produced during the resolution step, is described. The literature procedure is fraught with many difficulties including number of steps and hazardous reagents. We have developed a one pot process for the above-mentioned racemization of S -enantiomer. The basic objective is to convert S -enantiomer into the symmetrical glutarimide derivative followed by hydrolysis with an alkali. The transformation of 9 into glutarimide derivative ( 10 ) has been achieved with piperidine in refluxing toluene.",10.1021/op900064x,2009-05-18,0.5787955981184005
Organic Letters,Modular Synthesis of Rigid Polyacene Dimers for Singlet Fission,"An improved, modular synthesis of rigid, geometrically well-defined, alkyne-substituted tetracene (1) and pentacene (2) dimers is reported. The synthesis is rooted in sequential Diels-Alder reactions of a norbornyl tetraene with triisopropylsilylacetylene-substituted (TIPS-acetylene) quinone dienophiles. The incorporation of solubilizing and stabilizing TIPS-acetylene groups early in the synthesis affords a mild and reliable route, providing access, for the first time, to norbornyl-bridged pentacene dimers. A preliminary exploration of the excited state behavior of these molecules is also described.",10.1021/acs.orglett.7b03817,2018-01-05,0.5787932498904557
Tetrahedron,"Highly stereoselective one-step synthesis of 5-aryl- and 5-(2-styrenyl)-4,5-trans-epoxy-2(E)-pentenols employing an arsonium salt",,10.1016/0040-4039(91)80610-i,1991-08-01,0.5787902984350063
Synthesis,"Novel 1,2-Disubstituted Carbocyclic Nucleoside Analogues of Purine with a Cyclopentene Ring","A total and versatile synthesis of a new series of carbocyclic nucleoside analogues which are derivatives of purine with a 1,2-disubstituted cyclopentene ring (I) is described. The 6-chloropurine derivatives 3 and 9 were prepared by construction of the heterocyclic base about the primary amino group of the (±)-cis-2-amino-3-cyclopentenylmethanol (1), which was synthesized in good yield from cyclopentadiene in four steps. The substitution of a chlorine atom in the compounds 3 and 9 by an amino group (compounds 4 and 10) and by a hydroxyl group (compounds 5 and 11) was carried out with NH4OH or with NaOH, respectively.",10.1055/s-2002-35239,2002-01-01,0.5787898016126674
Journal of Organic Chemistry,Synthesis of Cryptophane-B: Crystal Structure and Study of Its Complex with Xenon,"Whereas the synthesis of the anti -cryptophane-A ( 1 ) derivative has been known for nearly 40 years, the preparation of its diastereomer (cryptophane-B according to Collet’s nomenclature) has never been reported. Thus, the synthesis of the cryptophane-B derivative represents a real challenge for chemists interested in the preparation of these hollow molecules. Herein, we describe a synthetic route that allows us to prepare cryptophane-B ( 2 ), albeit in a low yield. The X-ray crystallographic structure of this compound is described, and it reveals the presence of an ethanol molecule inside the cavity of the host. Finally, the ability of cryptophane-B to bind xenon in 1,1,2,2-tetrachloroethane- d 2 is also studied via hyperpolarized 129 Xe NMR.",10.1021/acs.joc.8b02246,2018-11-14,0.5787863749389314
Angewandte Chemie International Edition,Single‐Step Modular Synthesis of Unsaturated Morpholine <i>N</i>‐Oxides and Their Cycloaddition Reactions,"A single-flask procedure for the generation of α-keto-N-alkenylnitrones through a Chan-Lam coupling and subsequent spontaneous 6π electrocyclization of these intermediates for the synthesis of 2H-1,4-oxazine N-oxides has been developed for a variety of α-ketooximes and alkenylboronic acids. This transformation provides a new approach to C-substituted unsaturated morpholine derivatives that are poised to undergo further functionalization for the preparation of a diverse array of novel heterocyclic structures. The scope of the new method for the synthesis of 2H-1,4-oxazine N-oxides is discussed, in addition to initial studies describing the cycloaddition reactivity of these new heterocyclic intermediates.",10.1002/anie.201611791,2017-02-03,0.5787844884814339
Organic Letters,Synthesis of Medium Ring Heterocycles Using an Intramolecular Heck Reaction,"Historically, general convergent syntheses of medium ring heterocycles have been difficult to develop. Herein, we describe the synthesis of five classes of heterocycles: dihydrodibenzo[b,f]azepine, -oxocine, and -thiocine and dibenzo[b,f]azepine and -oxepine using a strategy of alkylation followed by highly selective intramolecular Heck arylation reaction. The hetero-tricyclic compounds were available in only two steps starting from commercially available starting materials.",10.1021/ol0487884,2004-07-27,0.5787840257137854
Journal of Organic Chemistry,"Rh-Catalyzed Asymmetric Hydrogenation of 1,2-Dicyanoalkenes","A highly efficient enantioselective hydrogenation of 1,2-dicyanoalkenes catalyzed by the complex of rhodium and f-spiroPhos has been developed. A series of 1,2-dicyanoalkenes were successfully hydrogenated to the corresponding chiral 1,2-dicyanoalkanes under mild conditions with excellent enantioselectivities (up to 98% ee). This methodology provides efficient access to the asymmetric synthesis of chiral diamines.",10.1021/acs.joc.6b02678,2016-12-13,0.5787829355488181
Journal of Organic Chemistry,Total Synthesis of the <i>Aspidosperma</i> Alkaloid (±)-Subincanadine F via a Titanium-Mediated Intramolecular Nucleophilic Acyl Substitution Strategy,The total synthesis of the bridge-fused Aspidosperma indole alkaloid (±)-subincanadine F has been accomplished in seven steps. The synthetic utility of a titanium-mediated intramolecular nucleophilic acyl substitution (INAS) reaction for the construction of the bridge-fused ring system was demonstrated.,10.1021/jo1015823,2010-09-16,0.5787799717467569
Synthesis,The First Total Synthesis of Pectinolide F,"The first total synthesis of the natural saturated α-pyrone pectinolide F has been accomplished from inexpensive, commercially available ( S )-ethyl lactate and but-3-yn-1-ol. The salient features of the synthesis are 2,2,6,6-tetramethylpiperidin-1-oxyl (TEMPO)–[bis(acetoxy)iodo]benzene oxidation, Sharpless asymmetric dihydroxylation, Grignard reaction, and partial hydrogenation of the triple bond.",10.1055/s-0033-1341231,2014-05-14,0.5787762413960325
Journal of Organic Chemistry,Synthesis of Nucleotide Diphosphate Uronic Acids via the Coupling of Activated Nucleotides with Uronic Acid-1-phosphates,"The stereoselective synthesis of nucleotide diphosphate (NDP) uronic acids from simple sugar precursors, including d-gluco-, d-galacto-, and d-mannopyranoside derivatives, is described. Key to this convergent synthesis is the coupling of unprotected uronic acid 1-phosphate with a nucleotide phosphorimidazolide to directly form the NDP-uronic acid, of which 11 derivatives were prepared. The coupling is compatible with the carboxylic acid functionality present in uronic acid-1-phosphates, with conversions of >95% and isolated yields typically above 60%. Key features of this work include (i) stereoselective synthesis of α-d-phosphoglycosides from perbenzylated α- and β-d-thioglycosides, (ii) selective and mild oxidation of galactose-, glucose-, and mannose-1-phosphates to the corresponding uronic acid-1-phosphate, and (iii) mild coupling conditions to directly provide nucleotide diphosphate uronic acids from unprotected uronic acid-1-phosphates and nucleotide phosphorimidazolides. This chemistry is currently in use to develop inhibitors of key enzymes involved in antibiotic resistance.",10.1021/acs.joc.5c00075,2025-03-25,0.5787738963179031
Journal of Organic Chemistry,Synthesis of Indeno-Quinolones and Their Functionalization toward 5-HT <sub>3</sub> Receptor,A practical and sustainable approach for the synthesis of bioactive indeno-quinolinones has been developed via tert -butyl hydroperoxide-mediated cross-dehydrogenative coupling. This metal and photocatalyst-free protocol proceeds under mild conditions and demonstrates broad substrate scope and operational simplicity. The potential for late-stage functionalization underscores the utility of this method in the efficient synthesis of bioactive compounds such as 5-HT 3 receptor and TAS-103 analogues.,10.1021/acs.joc.5c01433,2025-10-14,0.5787707816161901
Tetrahedron,A new route to 10-membered ring analogues of neocarzinostatin chromophore,,10.1016/s0040-4039(00)97131-4,1990-01-01,0.5787696128331088
Journal of Organic Chemistry,"Preparation of <i>anti</i>-Vicinal Amino Alcohols: Asymmetric Synthesis of <scp>d</scp>-<i>erythro</i>-Sphinganine, (+)-Spisulosine, and <scp>d</scp>-<i>ribo</i>-Phytosphingosine","Two variations of the Overman rearrangement have been developed for the highly selective synthesis of anti-vicinal amino alcohol natural products. A MOM ether-directed palladium(II)-catalyzed rearrangement of an allylic trichloroacetimidate was used as the key step for the preparation of the protein kinase C inhibitor D-erythro-sphinganine and the antitumor agent (+)-spisulosine, whereas the Overman rearrangement of chiral allylic trichloroacetimidates generated by the asymmetric reduction of an α,β-unsaturated methyl ketone allowed rapid access both to D-ribo-phytosphingosine and L-arabino-phytosphingosine.",10.1021/jo401211j,2013-06-24,0.578767568658538
European Journal of Organic Chemistry,Synthesis of Verbascoside: A Dihydroxyphenylethyl Glycoside with Diverse Bioactivity,"TMSOTf-mediated condensation of ethyl 4,6-O-benzylidene-1-thio-β-D-glucopyranoside (2) with peracetylated α-L-rhamnopyranosyl trichloroacetimidate donor 3a resulted in the formation of orthoester 4, which, after acetylation, rearranged into ethyl 3-O-(α-L-rhamnopyranosyl)-1-thio-β-D-glucopyranoside derivative 6a. The latter compound was converted into the corresponding trichloroacetimidate donors 8a–b. An alternative approach to trichloroacetimidate 8c commenced with the iodonium ion mediated glycosidation of ethyl 2,3,4-tri-O-benzoyl-1-thio-α-L-rhamnopyranside (15) with 1,2:5,6-diisopropylidene-D-glucofuranose (16) to afford disaccharide 17, which was transformed into 8c in five steps. Condensation of 8a–c with 2-[3,4-di-(tert-butyldimethyl-silyloxy)phenyl]ethanol (12) gave, after deacylation, key intermediate 14. Protecting-group manipulation of 14 and subsequent esterification of resulting 22 with 3,4-di-O-tert-butyldimethylsilylcaffeic acid (27) gave, after deprotection, verbascoside (1).",10.1002/(sici)1099-0690(199910)1999:10<2623::aid-ejoc2623>3.3.co;2-b,1999-10-01,0.5787613220406328
European Journal of Organic Chemistry,Synthesis of Verbascoside: A Dihydroxyphenylethyl Glycoside with Diverse Bioactivity,"TMSOTf-mediated condensation of ethyl 4,6-O-benzylidene-1-thio-β-D-glucopyranoside (2) with peracetylated α-L-rhamnopyranosyl trichloroacetimidate donor 3a resulted in the formation of orthoester 4, which, after acetylation, rearranged into ethyl 3-O-(α-L-rhamnopyranosyl)-1-thio-β-D-glucopyranoside derivative 6a. The latter compound was converted into the corresponding trichloroacetimidate donors 8a–b. An alternative approach to trichloroacetimidate 8c commenced with the iodonium ion mediated glycosidation of ethyl 2,3,4-tri-O-benzoyl-1-thio-α-L-rhamnopyranside (15) with 1,2:5,6-diisopropylidene-D-glucofuranose (16) to afford disaccharide 17, which was transformed into 8c in five steps. Condensation of 8a–c with 2-[3,4-di-(tert-butyldimethyl-silyloxy)phenyl]ethanol (12) gave, after deacylation, key intermediate 14. Protecting-group manipulation of 14 and subsequent esterification of resulting 22 with 3,4-di-O-tert-butyldimethylsilylcaffeic acid (27) gave, after deprotection, verbascoside (1).",10.1002/(sici)1099-0690(199910)1999:10<2623::aid-ejoc2623>3.0.co;2-k,1999-10-01,0.5787613220406328
Synthesis,"Synthesis of 6,6′-Diamino-2,2′-biquinoline and 2,2′-Bi-1,6-naphthyridine","High-yield synthesis and characterization of the new het- erocycles 6,6'-diamino-2,2'-biquinoline ( 3), 6,6'-bis(N,N-dimethyl- amino)-2,2'-biquinoline (4), and 2,2'-bi-1,6-naphthyridine ( 5) are described. The preparation of 3 and 4 is based on the coupling of 2- amino-6-chloroquinoline and 2-chloro-6-dimethylaminoquinoline in the presence of NiCl 2◊6H2O/PPh3/Zn in DMF (NiCRA). Com- pound 5 was synthesized through a condensation reaction of 4-ami- nopyridine-3-carbaldehyde and butane-2,3-dione.",10.1055/s-1999-6064,1999-06-01,0.5787505423809901
Angewandte Chemie International Edition,"Synthesis of 1,9‐Dideoxy‐pre‐axinellamine","Within reach: A 19-step route to 1,9-dideoxy-pre-axinellamine has been designed and executed. This key compound represents a hypothetical precursor to an entire family of alkaloid natural products.",10.1002/anie.200705913,2008-03-20,0.57874913458458
Tetrahedron,"A simple and efficient synthesis of (7E, 9E, 11Z, 13E)-(5S, 6R, 15S)-trihydroxyeicosatetraenoic acid (6R-lipoxin A)",,10.1016/s0040-4039(01)80684-5,1989-01-01,0.5787461175422316
Organic Letters,A Three-Step Catalytic Asymmetric Sequence from Alkynes to α-Silyloxyaldehydes and Its Application to a C22–C41 Fragment of Bastimolide A,"1,5-Polyol structures present challenges in stereocontrol, configurational assignment, and diastereomer separation; these are all compromised by remote stereochemical relationships. A configuration-encoded approach with alcohol configurations previously established within enantiopure building blocks offers a versatile solution to these issues. The iterative construction begins with α-silyloxyaldehydes; here, we introduce an enantioselective and step-economical route from alkynes to α-silyloxyaldehydes via silyl cation-induced ring opening of enol ester epoxides. This development enables an efficient configuration-encoded synthesis of the C22-C41 fragment of the bastimolides.",10.1021/acs.orglett.4c01310,2024-05-16,0.5787432917837156
Synthesis,"A Novel Synthesis of Clonidine, an Anti-Hypertensive Drug from<i>o</i>-Chloronitrobenzene","All articles of this category An elegant, cost-effective synthesis of clonidine ( 4 ) is reported from readily available starting materials. o -Chlorophenylhydroxylamine ( 2 ), obtained from o -chloronitrobenzene, is formylated to N -(2-chlorophenyl)-N-hydroxyformamide ( 3 ). In a one-pot procedure, 3 is converted to clonidine by chlorination with thionyl chloride and then with thionyl chloride/sulfuryl chloride, followed by condensation with ethylenediamine.",10.1055/s-1987-27847,1987-01-01,0.578742581483021
Synlett,A Short Homochiral Synthesis of Substituted Pyrrolidines,"All articles of this category A simple and efficient highly stereocontrolled route to trisubstituted vinylpyrrolidines like (3 S ,4 S )-1-benzyl-3,4-di-benzyloxy-2-vinylpyrrolidine ( 5 ) from monosaccharides is reported. The procedure, illustrated in the D - gluco series, involves treating methyl 6-bromohexopyranosides like methyl 4- O -benzoyl-2,3-di- O -benzyl-6-bromo-α- D -glycopyranoside ( 2 ) with zinc, sodium cyanoborohydride and benzylamine in propanol/water at reflux. Under these conditions, reductive ring opening of the bromosugar to an ω-alkenylaldehyde is followed by in situ reductive amination of the carbonyl with benzylamine and spontaneous intramolecular displacement of a C4-benzoate ester, now made allylic by the newly-formed alkene.",10.1055/s-1990-21142,1990-01-01,0.5787376393998489
Tetrahedron,[3.3.0] Pyrazolodinones: An efficient synthesis of a new class of synthetic antibacterial agents.,,10.1016/0040-4039(90)80153-d,1990-01-01,0.5787320316091681
Synlett,"Synthesis of Monofluoroalkenes via the Activation of Allylic C-F Bonds: A Novel Route to β-Aminofluoroalkenes Using Pd-Catalyzed Allylic Amination Reactions of 3,3-Difluoropropenes","This article portrays the development of a novel and efficient synthetic route to β-aminofluoroalkenes, from readily available 3,3-difluoropropenes and amines, that proceeds via the activation of an allylic C-F bond.",10.1055/s-0030-1259333,2011-01-25,0.5787302976513502
Synlett,"A Practical, Versatile Approach to Marine Furanosesquiterpenes. Synthesis of Siphonodictidine and Pleraplysillin-2","All articles of this category The first synthesis of siphonodictidine and a formal synthesis of pleraplysillin-2 have been accomplished in a highly concise and regiocontrolled manner by the use of 2-( tert -butyldimethylsiloxy)-3-methylfuran as the crucial building block, which was alkylated with 8-bromogeranyl acetate in the presence of silver trifluoroacetate.",10.1055/s-1990-21235,1990-01-01,0.5787285054612953
Tetrahedron,"Efficient ‘one-pot’ methodology for the synthesis of novel tetrahydro-β-carboline, tetrahydroisoquinoline and tetrahydrothienopyridine derivatives",,10.1016/j.tetlet.2013.08.135,2013-09-10,0.5787233372883073
Tetrahedron,Isolation of key intermediates during formation of oolongtheanins,,10.1016/j.tetlet.2013.10.069,2013-10-23,0.5787202526232648
Organic Letters,Ligand-Controlled Monoselective <i>C</i>-Aryl Glycoside Synthesis via Palladium-Catalyzed C–H Functionalization of <i>N</i>-Quinolyl Benzamides with 1-Iodoglycals,"A monoselective synthesis of aryl-C-Δ(1,2)-glycosides from 1-iodoglycals via palladium-catalyzed ortho-C-H activation of N-quinolyl benzamides has been developed. An amino acid derivative was used as a crucial ligand to improve the yield and monoselectivity of the coupling reaction. The utility of this protocol was demonstrated by a concise synthesis of key moieties of some natural products.",10.1021/acs.orglett.6b00566,2016-03-30,0.5787187177958326
Synthesis,"Application of Primary Allylamine Derivatives of Baylis-Hillman Adducts to Heterocyclic Synthesis: Generation of 5-Benzyl-4(3<i>H</i>)-pyrimidinones and 2-Benzylidene-2,3-dihydropyrrolizin-1-ones","The applications of the primary allylamines obtained from the acetyl derivative of Baylis-Hillman adducts of acrylate for the synthesis of heterocycles using robust reactions are described. In the first strategy, a one-pot synthesis of 5-benzyl-4(3H)-pyrimidinones have been achieved via N-formylation of the amines in the presence of neat formamide followed by ammonium formate-mediated cyclization. These pyrimidinones have been demonstrated to be excellent precursor to the 4-pyridinamine derivatives. In the second strategy, the synthesis of 2-benzylidene-2,3-dihydropyrrolizin-1-ones have been accomplished via treatment of allylamine with dimethoxyfuran followed by saponification and PPA-mediated intramolecular cyclization.",10.1055/s-2007-990929,2007-12-20,0.578718553686438
Journal of the American Chemical Society,"PtCl<sub>2</sub>-Catalyzed Rapid Access to Tetracyclic 2,3-Indoline-Fused Cyclopentenes:  Reactivity Divergent from Cationic Au(I) Catalysis and Synthetic Potential","A PtCl 2 -catalyzed 3,3-rearrangement/[3+2]-cycloaddition of propargylic 3-indoleacetates is developed. Besides the efficient formation of highly functionalized tetracyclic cyclopentenes, the reaction is dramatically divergent from that catalyzed by cationic Au I . Moreover, the synthetic potential of this method is demonstrated by a succinct synthesis of the tetracyclic core of vindolinine.",10.1021/ja074536x,2007-08-28,0.5787162210581288
Synthesis,Total Synthesis of Lamellarins U and A3 by Interrupting Halogen Dance,"Abstract A total synthesis of lamellarins U and A3 is described. The synthesis features the interruption of a halogen dance reaction of a metalated α,β-dibromopyrrole. The pyrrolylmagnesium reagent, generated by deprotonative metalation by using (TMP)MgCl·LiCl (TMP = 2,2,6,6-tetramethylpiperidide) as the base, was transmetalated to the corresponding organozinc species without causing the halogen dance reaction, which underwent a Negishi coupling to incorporate an aryl group onto the pyrrole ring. The arylated α,β-dibromopyrrole was then converted into lamellarins U and A3 through an α-selective halogen–magnesium exchange followed by carboxylation and subsequent palladium-mediated cyclization. The late-stage introduction of another aryl group was performed using a Kosugi–Migita–Stille coupling to provide lamellarins U and A3.",10.1055/a-1736-7337,2022-01-11,0.5787133190658005
Journal of Organic Chemistry,"Synthesis of a Sterically Crowded Atropisomeric 1,8-Diacridylnaphthalene for Dual-Mode Enantioselective Fluorosensing","An efficient synthetic route to a sterically crowded 1,8-diheteroarylnaphthalene-derived enantioselective fluorosensor that operates in two different detection modes utilizing fluorescence lifetime and intensity has been developed. Screening of palladium-catalyzed Negishi, Kumada, Suzuki, Hiyama, and Stille coupling methods showed that the latter affords highly congested 1,8-diarylnaphthalenes in superior yields. Despite severe steric hindrance, axially chiral 1,8-bis(3-(3',5'-dimethylphenyl)-9-acridyl)naphthalene, 1, was obtained in 68% yield from 1,8-dibromonaphthalene, 14, and 3-(3',5'-dimethylphenyl)-9-tributylstannylacridine, 13, via two consecutive Stille cross-coupling steps using tetrakis(triphenylphosphine)palladium(0) as catalyst in the presence of copper(II) oxide. The preparation of 1 involved formation of 4-(3',5'-dimethylphenyl)-2-chlorobenzoic acid, 7, through microwave-assisted Suzuki coupling of 4-bromo-2-chlorobenzoic acid, 10, and 3,5-dimethylphenylboronic acid, 11, followed by regioselective amination with aniline and acridine ring construction in phosphorus oxybromide. Lithiation, subsequent treatment with trimethylstannyl chloride, and Stille cross-coupling then completed the five-reaction sequence providing 1 in 57% overall yield. The enantiomers of 1 were separated by semipreparative HPLC on a (R,R)-Whelk-O 1 column and successfully employed in enantioselective fluorosensing of N-t-Boc-protected serine, 20, glutamine, 22, proline, 23, and 2-hydoxy-2-methylsuccinic acid, 21. Fluorescence titration experiments with 23 revealed that both static and dynamic quenching occur with distinctive enantioselectivity. Addition of (R)-23 to a solution of (+)-1 in acetonitrile resulted in stronger fluorescence quenching than titration with the (S)-enantiomer of 23. The fluorescence lifetime, tau, of 1 was determined as 18.8 ns and steadily decreased to 7.5 and 6.8 ns in the presence of 0.1 M of (S)-23 and (R)-23, respectively.",10.1021/jo0600353,2006-03-01,0.5787102913137135
Synthesis,Two Convergent Approaches toward Novel Carbocyclic C-Nucleosides,"Two convergent methodologies for construction of novel carbocyclic C-nucleosides allowing the syntheses of derivatives with uracil heterobase substituted at the position C-5 as well as C-6 were developed. The crucial step of the first methodology was the reaction of (6-chloro-2,4-dimethoxypyrimidin-5-yl)lithium, the nucleobase precursor, with suitable ketones, the carbocyclic pseudosugar precursors. The second approach was based on the copper-catalyzed cross-coupling between magnesiated pyrimidine and appropriate allyl chlorides. These methodologies were applied for the synthesis of novel carbocyclic C-nucleosides bearing cyclohexene or cyclohexane as a pseudosugar.",10.1055/s-0030-1258271,2010-09-28,0.578708904341911
Journal of Organic Chemistry,<i>De Novo</i> Enantioselective Synthesis of Hexafluorinated <scp>d</scp>-Glucose,"High Resolution Image Download MS PowerPoint Slide We report a de novo enantioselective synthesis of 2,3,4-trideoxy-2,2,3,3,4,4-hexafluoro- d - glycero -hexopyranose (hexafluorinated d -glucose), an iconic polar hydrophobic glycomimetic. The 12-step synthesis features robust and reproducible chemistry and was achieved by incorporating an asymmetric dihydroxylation step to install the stereogenic center with excellent enantioselectivity (95:5 er ). Virtual enantiopurity (>99.5% ee ) was further reached using a simple crystallization procedure and the absolute confirmation was ascertained by X-ray analysis. The synthetic route also allowed access to the novel hexafluorinated heptose derivative 2,3,4-trideoxy-2,2,3,3,4,4-hexafluoro- l - threo -heptopyranose.",10.1021/acs.joc.4c01724,2024-09-13,0.5787088156696779
Angewandte Chemie International Edition,Direct Asymmetric Reductive Amination for the Synthesis of Chiral β‐Arylamines,The highly efficient and direct asymmetric reductive amination of arylacetones catalyzed by an iridium complex for the preparation of enantiomerically pure β-arylamines is described. The monodentate phosphoramidite ligand exhibits superb reactivity (TONs of up to 20 000) and enantioselectivity (up to 99 % ee). Additives played important roles in this reductive coupling reaction.,10.1002/anie.201601025,2016-03-16,0.5786956931131895
Tetrahedron,Intramolecular asymmetric Pummerer reactions as a key step in the synthesis of bicyclic precursors of anthracyclinones,,10.1016/s0040-4039(99)02025-0,2000-01-01,0.5786940076207578
Journal of Organic Chemistry,"Prins Cascade Cyclization for the Synthesis of 1,9-Dioxa-4-azaspiro[5.5]undecane Derivatives","A novel Prins cascade process for the synthesis of 1,9-dioxa-4- azaspiro[5.5]undecane derivatives by the coupling of aldehydes with N-(4-hydroxy-2-methylenebutyl)-N-(2-hydroxyethyl)-4-methylbenzenesulfonamide has been developed. This is the first report of the synthesis of spiromorpholinotetrahydropyran derivatives through a Prins bicyclization.",10.1021/jo4027534,2014-02-17,0.5786914819352421
Journal of Organic Chemistry,"Asymmetric Synthesis of Methoxylated Ether Lipids: A Glyceryl Glycidyl Ether Key Building Block Design, Preparation, and Synthetic Application","The report describes the preparation and use of a double-C3 building block intended as a head group synthon in the synthesis of saturated, mono-, and polyunsaturated 1- O -alkyl- sn -glycerol type methoxylated ether lipids (MELs). The resulting head piece, an enantiopure isopropylidene-protected glyceryl glycidyl ether diastereomer, was accomplished in 49% yield (max 50%) from a 1:1 diastereomeric mixture obtained from R -solketal and racemic epichlorohydrin after treatment with the Jacobsen ( S, S )-Co(III)salen catalyst for the hydrolytic kinetic resolution of terminal epoxides. The diol hydrolytic product obtained in 47% yield from the unwanted diastereomer was reconverted into epoxide with an inversion of configuration in a three-step operation involving a highly regioselective lipase. This enabled the recovery of a substantial amount of diastereopure material after a subsequent treatment with the Jacobsen catalyst to furnish the oxirane head piece in altogether 72% yield of higher than 99% diastereomeric purity. A modified synthesis of a monounsaturated 16:1 MEL confirmed the correct stereochemistry and excellent enantiopurity of the head piece and resulted in a dramatic improvement in yields, efficiency, and economy of the synthesis.",10.1021/acs.joc.2c01515,2022-08-29,0.5786840085901758
Journal of the American Chemical Society,Nickel(0)-Catalyzed Enantio- and Diastereoselective Synthesis of Benzoxasiloles: Ligand-Controlled Switching from Inter- to Intramolecular Aryl-Transfer Process,"A highly enantioselective synthesis of 3-aryl-, vinyl-, and alkynyl-2,1-benzoxasiloles (up to 99.9% ee and 99% yield) was achieved via the sequential activation of an aldehyde and a silane by nickel(0). This strategy was applied to a simultaneous generation of carbon- and silicon-stereogenic centers with excellent selectivity (dr = 99:1) via diastereotopic aryl transfer. Initial mechanistic studies revealed the complete switching of an aryl-transfer process from an intermolecular (racemic synthesis in the presence of IPr) to an intramolecular (enantioselective synthesis using chiral NHC, L5) fashion. A plausible rationale for the switching of the aryl-transfer process is given by a preliminary DFT calculation, which suggests that the coordination of 1 to the nickel(0)/L5 fragment in an η(2)-arene:η(2)-aldehyde fashion would be a key to the intramolecular process, while the formation of the corresponding intermediate is not possible in the presence of IPr. Owing to the chemically labile nature of its C-Si and O-Si bonds, enantioenriched benzoxasiloles are utilized for the synthesis of chiral building blocks and antihistaminic and anticholinergic drug molecules such as (R)-orphenadrine and (S)-neobenodine with no erosion of the enantiomeric excess.",10.1021/jacs.5b07827,2015-08-24,0.5786836059085392
Journal of Organic Chemistry,A Concise Access to 3-Substituted 2-Pyrones.,The development of a modular synthesis of 3-substituted-2-pyrones is described. The attainment of this strategy hinges on a new electrophilic pyrone derivative which can be readily prepared on a multigram scale and which performs very competently in metal-catalyzed cross-coupling reactions with a variety of nucleophiles.,10.1021/jo101843a,2010-10-29,0.578683118936189
Synthesis,A One-Pot β-Chloro-N′-tosylamidination of Olefins with Chloramine-T,A new method for the direct synthesis of β-chloro-N′-tosylamidines from olefins using chloramine-T and trifluoromethanesulfonic acid is described.,10.1055/s-0030-1260021,2011-04-28,0.5786821986651088
Journal of the American Chemical Society,"Evolution of the Total Synthesis of (−)-Okilactomycin Exploiting a Tandem Oxy-Cope Rearrangement/Oxidation, a Petasis−Ferrier Union/Rearrangement, and Ring-Closing Metathesis","An effective, asymmetric total synthesis of the antitumor antibiotic (-)-okilactomycin (1), as well as assignment of the absolute configuration, has been achieved exploiting a convergent strategy. Highlights of the synthesis include a diastereoselective oxy-Cope rearrangement/oxidation sequence to install the C(1) and C(13) stereogenic centers, a Petasis-Ferrier union/rearrangement to construct the highly functionalized tetrahydropyranone inscribed within the 13-membered macrocycle ring, employing for the first time a sterically demanding acetal, an intramolecular chemoselective acylation to access an embedded bicyclic lactone, and an efficient ring-closing metathesis (RCM) reaction to generate the macrocyclic ring.",10.1021/ja8084669,2009-01-26,0.5786804452137743
Organic Letters,Stereoselective Synthesis of the Monomeric Unit of Actin Binding Macrolide Rhizopodin,"An efficient, scalable, and stereocontrolled synthesis of the entire carbon framework of an actin binding dimeric macrolide rhizopodin has been accomplished in its protected form. The key features of our synthesis include a titanium catalyzed anti acetal aldol reaction, a substrate controlled diastereoslelective prenyl stannylation, a Mukaiyama aldol reaction, an indium mediated diastereoselective propargylation, and an advanced stage Stille coupling reaction.",10.1021/ol301103d,2012-05-18,0.5786770732340066
European Journal of Organic Chemistry,"Methodology for Synthesis of Enantiopure 3,5‐Disubstituted Pyrrol‐2‐ones","Abstract A new synthetic route towards chiral 3,5‐disubstituted pyrrol‐2‐ones by starting from amino acids has been developed. The sequence features the conversion of amino acids into their corresponding alkynoic acid derivative followed by a Pd‐catalyzed hydrostannylation of the triple bond and Stille cross‐coupling reaction. A series of lactam analogues of antifungal 3‐(aryl)‐5‐hydroxymethyl‐2,5‐dihydrofuran‐2‐ones have thus been prepared.",10.1002/ejoc.201500620,2015-07-17,0.5786715425674945
Journal of the American Chemical Society,"Streamlined Total Synthesis of Shishijimicin A and Its Application to the Design, Synthesis, and Biological Evaluation of Analogues thereof and Practical Syntheses of PhthNSSMe and Related Sulfenylating Reagents","Shishijimicin A is a scarce marine natural product with highly potent cytotoxicities, making it a potential payload or a lead compound for designed antibody-drug conjugates. Herein, we describe an improved total synthesis of shishijimicin A and the design, synthesis, and biological evaluation of a series of analogues. Equipped with appropriate functionalities for linker attachment, a number of these analogues exhibited extremely potent cytotoxicities for the intended purposes. The synthetic strategies and tactics developed and employed in these studies included improved preparation of previously known and new sulfenylating reagents such as PhthNSSMe and related compounds.",10.1021/jacs.8b06955,2018-09-14,0.5786712254834083
Journal of Organic Chemistry,Biomimetic Synthesis of Myrtucommulones D–E,"A concise and efficient biomimetic synthesis of myrtucommulones D-E has been achieved, proceeding in just 6-7 linear steps from readily available biogenetic building blocks. The key feature of the synthesis was the Zn-mediated skeletal rearrangement reaction, without the need for rare metal photocatalysts and visible light. Based on this biomimetic synthesis, four compounds demonstrated moderate to excellent cytotoxic activities against osteosarcoma cells (U2OS and 143B).",10.1021/acs.joc.5c00859,2025-06-13,0.578668819697536
European Journal of Organic Chemistry,"Efficient Synthesis of Benzofurans Utilizing [3,3]‐Sigmatropic Rearrangement Triggered by <i>N</i>‐Trifluoroacetylation of Oxime Ethers: Short Synthesis of Natural 2‐Arylbenzofurans","Abstract A new synthetic method for the preparation of benzofurans has been developed. The key step of this method is the [3,3]‐sigmatropic rearrangement of N ‐trifluoroacetyl‐ene‐hydroxylamines, which was triggered by acylation of oxime ethers. TFAA has been proved to be the best reagent to induce [3,3]‐sigmatropic rearrangement for the synthesis of cyclic oracyclic dihydrobenzofurans. On the other hand, the TFAT‐DMAP system is found to be the most effective for constructing various benzofurans. Synthetic utility of this reaction is demonstrated by the short synthesis of natural benzofurans without protection of the hydroxy group. The synthesis of Stemofuran A was accomplished via condensation of ketones with aryloxyamine and subsequent reaction with TFAT‐DMAP in a four‐step synthesis with 72 % overall yield. Similarly, Eupomatenoid 6 and Coumestan were synthesized through the reaction of oxime ether with TFAT‐DMAP. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2007)",10.1002/ejoc.200601001,2007-01-25,0.5786672094735348
Angewandte Chemie International Edition,A Novel Route to Fulvene Complexes of Titanium—Diastereoselective Complexation of Pentafulvenes to Cyclopentadienyltitanium Fragments,,10.1002/1521-3773(20010601)40:11<2056::aid-anie2056>3.3.co;2-b,2001-06-01,0.5786646342130217
Angewandte Chemie International Edition,Enantioselective Synthesis of Cyclopropanes by Aldehyde Homologation,"An efficient method for the enantioselective preparation of structurally diverse cyclopropanes has been developed. Sequential homoaldol coupling and activation steps result in a three-carbon homologation of an aldehyde to give a nonracemic, stereochemically rich cyclopropylcarboxaldehyde (see scheme).",10.1002/anie.200461106,2004-12-09,0.5786572271648105
Journal of the American Chemical Society,Concise Synthetic Approaches for the Laurencia Family: Formal Total Syntheses of (±)-Laurefucin and (±)-<i>E</i>- and (±)-<i>Z</i>-Pinnatifidenyne,"Herein is presented a cohesive strategy to rapidly fashion diverse members of the lauroxocane family of natural products, leading to the shortest syntheses of any member to date. These efforts include racemic formal total syntheses of laurefucin and E- and Z-pinnatifidenyne as well as a facile preparation of the oxocene core of 3E-dehydrobromolaurefucin. The key elements of the design are novel diastereoselective ring-expanding bromoetherifications of tetrahydrofurans triggered by a unique bromonium source (BDSB, Et(2)SBr·SbBrCl(5)) and strategically positioned nucleophilic traps, where altering the identity and position of these traps affords diverse functionality on the eight-membered ring backbone. Its biogenetic relevance is also discussed in light of the range of substrates that successfully undergo this key rearrangement.",10.1021/ja3076988,2012-10-11,0.5786562723667452
Organic Letters,Enantiospecific Formal Total Synthesis of (+)-Fawcettimine,"The diastereospecific attack of the silyl enol ether on the activated cyclopropyl diester 27 generated the hydrindanone 28 with complete stereocontrol. Thermal decarbomethoxylation of 28 gave the monoester 29, a key intermediate in Heathcock's synthesis, thereby completing a formal total synthesis of (+)-fawcettimine 1. The analogous cyclization of 33, the diastereomer of 27, afforded the diastereomeric diester 34, thereby demonstrating that the cyclization process is diastereospecific.",10.1021/ol1009762,2010-06-01,0.5786549173879845
Tetrahedron,"Efficient asymmetric synthesis of α-amino acids through hydrogenation of α,β-dehydroamino acid residue in cyclic dipeptides",,10.1016/s0040-4039(01)86625-9,1979-01-01,0.5786548828562307
Journal of the American Chemical Society,The Total Synthesis of (+)-Migrastatin,"The first total synthesis of (+)-migrastatin, a macrolide natural product with interesting antimetastatic properties, has been accomplished. Our concise and flexible approach utilizes a Lewis acid-catalyzed diene aldehyde condensation to install the three contiguous stereocenters and the trisubstituted (Z)-alkene of migrastatin. Construction of the two remaining stereocenters and incorporation of the glutarimide-containing side chain have been achieved via an anti-selective aldol reaction, followed by a Horner-Wadsworth-Emmons olefination. Finally, the assembly of the macrocycle has been realized by a highly (E)-selective ring-closing metathesis.",10.1021/ja0349103,2003-04-25,0.5786509985030802
Synthesis,"Reductive Condensation of a Nitro Group with Carboxylic Acids Promoted by Phosphorus(III) Compounds: A Short Route to 5H-Dibenzo[b,e][1,4]diazepin-11(10H)-ones","Tributyl- or triphenylphosphine promotes a one-pot, three-step method for the synthesis of differently substituted dibenzodiazepinones from N-aryl-2-nitroanilines. Pyridine analogues and the corresponding thiazepinones can also be formed using this method. The process involves deoxygenation of the nitro group, then formation of an iminophosphorane intermediate and its intramolecular condensation with a carboxyl group placed in the N-aryl group. The role of the carboxyl group in the formation of the iminophosphorane and the mode of cyclization are discussed.",10.1055/s-0040-1707347,2020-07-21,0.5786464016892673
Synthesis,A One-Step Synthesis of Cyclic α-Diazoketones,,10.1055/s-1980-29022,1980-01-01,0.5786288694351505
Tetrahedron,"Synthetic entry to the ABCD ring fragment of gymnocin-A, a cytotoxic marine polyether",,10.1016/s0040-4039(03)00949-3,2003-05-12,0.578627086795747
Journal of Organic Chemistry,"Probes for Narcotic Receptor-Mediated Phenomena. 33.<sup>1</sup> Construction of a Strained <i>trans</i>-5,6-Ring System by Displacement of a Nitro-Activated Aromatic Fluorine. Synthesis of the Penultimate Oxide-Bridged Phenylmorphans","The synthesis of the ortho- and para-e isomers in the oxide-bridged 5-phenylmorphan series of rigid tetracyclic compounds was accomplished via rac-5-(2-fluoro-5-nitrophenyl)-2-methyl-2-azabicyclo[3.3.1]nonan-9beta-ol ((+/-)-10), an intermediate containing an aromatic nitro-activated fluorine atom. The fluorine atom was used as the leaving group for the formation of the strained tetracyclic trans-fused 5,6-ring system in rac-(1alpha,4aalpha,9aalpha)-1,3,4,9a-tetrahydro-2-methyl-6-nitro-2H-1,4a-propanobenzofuro[2,3-c]pyridine ((+/-)-11), although preference for cis ring fusion during the formation of tricyclic tetra- and hexahydrodibenzofurans has been well-documented. Single-crystal X-ray crystallographic study of the desired para-e isomer ((+/-)-2), as well as of two intermediates in its synthesis, provided assurance of the correct structures. The e-isomers are among the last of the 12 oxide-bridged 5-phenylmorphans to be synthesized. We envisioned the syntheses of these rigid, tetracyclic compounds in order to determine the three-dimensional pattern of a ligand that would enable interaction with opioid receptors as agonists or antagonists.",10.1021/jo040159k,2004-07-02,0.5786270857725878
Tetrahedron,Stereospecific formation of a substituted trans-decaline as an intermediate for the synthesis of clerodane insect antifeedants,,10.1016/0040-4039(81)80153-0,1981-01-01,0.5786255331140485
Journal of Organic Chemistry,Application of Cp<sub>2</sub>TiCl-Promoted Radical Cyclization: A Unified Strategy for the Syntheses of Iridoid Monoterpenes,"An expedient approach toward the unified total syntheses of (+)-iridomyrmecin, (-)-isoiridomyrmecin, (+)-7- epi-boschnialactone, (+)-teucriumlactone, and (-)-dolichodial in chirally pure forms starting from readily available (+)-β-citronellene is delineated combining step economy and simplicity. Highlights include a Ti(III)-mediated reductive epoxide opening-cyclization for the construction of the core cyclopenta[ c]pyran skeleton of the iridoid lactones with complete diastereoselectivity for the newly created bridgehead stereogenic centers. Subsequent transformations facilitate a short access to (+)-teucriumlactone and (-)-dolichodial and formal access to potentially other iridoids.",10.1021/acs.joc.8b00752,2018-05-16,0.5786252932006829
Tetrahedron,"γ-Butyltelluro-2-butanol: a route to reactive 1,4-dianion intermediates",,10.1016/j.tetlet.2005.05.002,2005-05-24,0.5786240045857348
Tetrahedron,A new selective reduction of nitroalkenes into enamides,,10.1016/0040-4039(96)00078-0,1996-03-01,0.5786160599667911
Organic Letters,Total Synthesis of the Proposed Structure of Marineosin A,"A total synthesis of a proposed structure of marineosin A has been achieved. The key steps involve Lewis acid catalyzed spirocyclizaton, ring-closing metathesis, Paal-Knorr pyrrole synthesis, and a Vilsmeier-Haack type reaction with Tf2O.",10.1021/acs.orglett.6b00632,2016-04-25,0.5786159078956892
Synlett,Total Synthesis of Cyclophellitol from L-Quebrachitol,"All articles of this category Cyclophellitol [1L-(1,3/2,4,5,6)-4,5-epoxy-6-(hydroxy-methyl)cyclohexane-1,2,3-triol] , a ß-glucosidase inhibitor, has been synthesized enantiospecifically from a naturally abundant cyclitol, L-quebrachitol (1L-2- O -methyl- chiro -inositol), via a Peterson olefination and an aluminum trichloride-tetrabutylammonium iodide mediated demethylation.",10.1055/s-1991-20895,1991-01-01,0.578615616010182
Organic Letters,A Route to Highly Functionalized β-Enaminoesters via a Domino Ring-Opening Cyclization/Decarboxylative Tautomerization Sequence of Donor–Acceptor Cyclopropanes with Substituted Malononitriles,An unprecedented and domino synthetic strategy for the synthesis of highly functionalized carbocyclic β-enaminoesters bearing an all-carbon quaternary center via Yb(OTf)3-catalyzed ring-opening cyclization/decarboxylative tautomerization of donor-acceptor cyclopropanes with 2-alkyl malononitriles in excellent yields is described. The products are obtained as a single diastereomer in most cases where the nitrile and aryl groups are aligning in a cis orientation across the ring.,10.1021/ol5007218,2014-04-08,0.5786143126103495
Tetrahedron,Synthesis in the diterpene alkaloid series - II. A total synthesis of the garrya alkaloids,,10.1016/s0040-4039(00)70405-9,1964-01-01,0.5786108860714185
European Journal of Organic Chemistry,Synthesis of Oxaphosphinane‐Based Pseudodisaccharides,The synthesis of pseudodisaccharides based on an oxaphosphinane heterocycle is described. Disaccharide mimetics 5 and 6 were readily obtained through glycosylation of a hydroxy group with appropriately protected furanosyl or pyranosyl carbohydrates using a trichloroacetamidate coupling strategy. Selective or complete deprotection then produced the chiral pseudodisaccharides in good yields.,10.1002/ejoc.201700878,2017-09-27,0.57861070218338
Organic Letters,"Enantioselective Synthesis of Allenamides via Sulfimide [2,3]-Sigmatropic Rearrangement","Chiral allenamides are prepared with high levels of enantiomeric purity by [2,3]-sigmatropic rearrangement of propargylic sulfimides. The required branched propargylic sulfides are prepared by an enantioselective organocatalytic aldehyde alpha-sulfenylation followed by Corey-Fuchs alkynylation.",10.1021/ol900146s,2009-03-02,0.5786063299622307
Tetrahedron,"A photochemical route to the unsaturated β-lactam, N-methyl-azetinone: A thermally labile ring-system",,10.1016/s0040-4039(00)72135-6,1975-01-01,0.5785923131907981
Organic Letters,Enantioselective Total Synthesis of (+)-Neosymbioimine,[reaction: see text] The enantioselective total synthesis of (+)-neosymbioimine was accomplished in 18 steps from (-)-(S)-citronellol utilizing an organocatalytic alpha-oxidation of aldehyde 6. The carbon core was constructed by a tandem Horner-Wadsworth-Emmons (HWE) reaction and an intramolecular Diels-Alder cyclization. All double bonds of 12 were made in a stereoselective manner by Wittig-type reactions. Selective formation of the monosulfate monoester was accomplished by one-pot excessive sulfation followed by kinetic hydrolysis of bissulfate 18 in 79% yield.,10.1021/ol070049a,2007-03-23,0.5785823635400924
Tetrahedron,Chiral aziridine ring opening: facile synthesis of (R)-mexiletine and (R)-phenoxybenzamine hydrochloride,,10.1016/j.tetlet.2015.07.032,2015-07-16,0.578577110578943
Synlett,Oxidative Dearomatization of o-Hydroxymethylphenol and Intramolecular π4s+π2s Cycloaddition: An Expedient Synthesis of a Tricyclic Intermediate for Platencin,A synthesis of a tricyclic intermediate for platencin from a simple aromatic precursor is described. Oxidative dearomatization and intramolecular Diels–Alder reaction are key features of the approach.,10.1055/s-0033-1339196,2013-06-20,0.5785751040124325
Angewandte Chemie International Edition,Stereocontrolled Synthesis of Adjacent Acyclic Quaternary‐Tertiary Motifs: Application to a Concise Total Synthesis of (−)‐Filiformin,"Lithiation/borylation methodology has been developed for the synthesis of acyclic quaternary-tertiary motifs with full control of relative and absolute stereochemistry, thus leading to all four possible isomers of a stereodiad. A novel intramolecular Zweifel-type olefination enabled acyclic stereocontrol to be transformed into cyclic stereocontrol. These key steps have been applied to the shortest enantioselective synthesis of (-)-filiformin to date (9 steps) with full stereocontrol.",10.1002/anie.201400944,2014-04-22,0.5785713592357798
Angewandte Chemie International Edition,Enantioselective Catalysis Coupled with Stereodivergent Cyclization Strategies Enables Rapid Syntheses of (+)‐Limaspermidine and (+)‐Kopsihainanine A,"Enantioselective Pd-catalyzed allylic alkylations of dihydropyrido[1,2-a]indolone (DHPI) substrates were used to construct the C20-quaternary stereocenters of multiple monoterpene indole alkaloids. Stereodivergent Pictet-Spengler and Bischler-Napieralski cyclization/reduction cascades furnish the cis- and trans-fused azadecalin subunits present in Aspidosperma and Kopsia alkaloids, respectively, en route to highly efficient syntheses of (+)-limaspermidine and (+)-kopsihainanine A.",10.1002/anie.201707304,2017-09-05,0.5785646318679486
Organic Letters,Intramolecular Condensation via an <i>o</i>-Quinone Methide: Total Synthesis of (±)-Heliol,An acid-catalyzed intramolecular [4 + 2] cycloaddition of a non-natural bisabolene is reported. The key cyclocondensation was developed to access cyclic sesquiterpenes from linear phenolic precursors by generating a reactive o-quinone methide intermediate to initiate a cascade reaction. The new method was applied to the first total synthesis of (±)-heliol.,10.1021/ol301092w,2012-05-31,0.5785645177405109
European Journal of Organic Chemistry,Approach Toward a Generic Treatment of Gram-Negative Infections: Synthesis of Haptens for Catalytic Antibody Mediated Cleavage of the Interglycosidic Bond in Lipid A,"In order to develop a generic treatment for infections with Gram-negative bacteria, we developed a synthesis of 2-acylamino-deoxynojirimycin derivatives (17, 18, 19 and 20), which will be used as haptens for raising catalytic antibodies capable of hydrolyzing the interglycosidic bond in the lipid A moiety of endotoxins. A key intermediate in the preparation of compounds 17, 18, 19 and 20 is 3,4,6-tri-O-benzyl-2-[(benzyloxycarbonyl)amino]-2-deoxy-D-glucono-δ-lactam (6), which was prepared from known 3,4,6-tri-O-benzyl-2-[(benzyloxycarbonyl)amino]-2-deoxy-D-glucosamine (1) in four steps in 47% overall yield. Antibodies were generated against 2-[(6-aminohexanoyl)amino]-2-deoxy-D-glucono-δ-lactam (17) coupled to the carrier protein bovine serum albumin.",10.1002/(sici)1099-0690(199910)1999:10<2593::aid-ejoc2593>3.0.co;2-c,1999-10-01,0.5785603995178153
European Journal of Organic Chemistry,Approach Toward a Generic Treatment of Gram-Negative Infections: Synthesis of Haptens for Catalytic Antibody Mediated Cleavage of the Interglycosidic Bond in Lipid A,"In order to develop a generic treatment for infections with Gram-negative bacteria, we developed a synthesis of 2-acylamino-deoxynojirimycin derivatives (17, 18, 19 and 20), which will be used as haptens for raising catalytic antibodies capable of hydrolyzing the interglycosidic bond in the lipid A moiety of endotoxins. A key intermediate in the preparation of compounds 17, 18, 19 and 20 is 3,4,6-tri-O-benzyl-2-[(benzyloxycarbonyl)amino]-2-deoxy-D-glucono-δ-lactam (6), which was prepared from known 3,4,6-tri-O-benzyl-2-[(benzyloxycarbonyl)amino]-2-deoxy-D-glucosamine (1) in four steps in 47% overall yield. Antibodies were generated against 2-[(6-aminohexanoyl)amino]-2-deoxy-D-glucono-δ-lactam (17) coupled to the carrier protein bovine serum albumin.",10.1002/(sici)1099-0690(199910)1999:10<2593::aid-ejoc2593>3.3.co;2-3,1999-10-01,0.5785603995178153
Journal of Organic Chemistry,Asymmetric Synthesis of Metallocenes through Enantioselective Addition of Organolithium Reagents to 6-(Dimethylamino)fulvene,"Enantioselective addition of aryllithiums 2a-d (Ar = Ph (a), 2-MeC(6)H(4) (b), 2-MeOC(6)H(4) (c), 1-naphthyl (d)) to 6-(dimethylamino)fulvene (1) in the presence of (-)-sparteine in toluene at -78 degrees C generated chiral cyclopentadienyllithiums (4) substituted with an N,N-dimethylamino(aryl)methyl group, where the enantioselectivities are 51, 91, 90, and 83% for 4a, 4b, 4c, and 4d, respectively. Treatment of the chiral cyclopentadienides 4 with FeCl(2) or Fe(acac)(2) gave ferrocenes, which contain an N,N-dimethylamino(aryl)methyl side chain on both of the cyclopentadienyl rings. The enantiomeric purity of the chiral ferrocenes 7 thus obtained is 99% ee or higher for those containing a 2-MeC(6)H(4) (7b) or a 2-MeOC(6)H(4) (7c) group.",10.1021/jo0111199,2002-04-05,0.5785585245731755
Angewandte Chemie International Edition,A Three-Step Entry to the Aspirochlorine Family of Antifungal Agents,"The quest for superior antifungal agents will be aided by the unprecedented sulfur migration of an epidithioketopiperazine (EDKP) in a highly stereoselective manner and in high yield. The rearrangement provides a short route to compounds in the same family as aspirochlorine (1), a potent inhibitor of fungal protein synthesis. In this family one of the dithio sulfur atoms is anchored to a dihydrobenzofuran ring that is spiro fused to the piperazine ring.",10.1002/1521-3773(20001103)39:21<3866::aid-anie3866>3.0.co;2-e,2000-11-03,0.5785573585536765
Organic Letters,Total Syntheses of Ganodilactone and Related <i>Ganoderma</i>-Derived Meroterpenoid Dimers via Intramolecular Vinylogous Michael Addition,"Herein, we describe the first total syntheses of four Ganoderma-derived meroterpenoid dimers: ganodilactone, spirocochlealactone A, and dimercochlearlactones I and J. Highly substituted 5′ H -spiro[chromane-4,2′-furan]-2,5′-dione core skeleton of these natural products was efficiently constructed through intramolecular vinylogous Michael addition reaction as a pivotal step. Starting from commercially available compounds, dimercochlearlactones I and J were synthesized with the longest linear sequence (LLS) of eight steps, whereas ganodilactone and spirocochlealactone A were synthesized with an LLS of 11 steps.",10.1021/acs.orglett.5c01154,2025-07-09,0.5785548441333154
Journal of Organic Chemistry,"Fe-Catalyzed One-Pot Synthesis of 1,3-Di- and 1,3,5-Trisubstituted Pyrazoles from Hydrazones and Vicinal Diols","An iron-catalyzed route for the regioselective synthesis of 1,3- and 1,3,5-substituted pyrazoles from the reaction of diarylhydrazones and vicinal diols has been developed. This method was found to be practical with wide substrate scope.",10.1021/jo301770k,2012-09-21,0.5785519104972888
Tetrahedron,Synthesis of dimeric Lewis X antigenic determinant with azido-type spacer arm by a sequence of regioselective glycosylation steps,,10.1016/s0040-4039(98)02104-2,1998-12-01,0.5785493750486302
Organic Letters,"Efficient Convergent Synthesis of 1α,25-Dihydroxyvitamin D<sub>3</sub> and Its Analogues by Suzuki−Miyaura Coupling","[reaction: see text] 1alpha,25-Dihydroxyvitamin D(3) was synthesized by the Suzuki-Miyaura coupling of the A-ring intermediate 1, which was efficiently prepared from readily available 1,7-enyne 2, with the corresponding boronate compound of the C,D-ring portion. The method was applied to prepare des-C,D analogues of 1alpha,25-dihydroxyvitamin D(3).",10.1021/ol0274007,2003-01-28,0.5785493689736271
Journal of the American Chemical Society,A convergent synthetic route to the tunicamycin antibiotics. Synthesis of (+)-tunicamycin V,"The tunicamycins are a family of natural products represented generally by structure 1, wherein R indicates one of several long-chain branched, linear, saturated or unsaturated acyl substituents. They elicit a considerable range of biological responses including antimicrobial, antifungal, antiviral, and antitumor activities. Their ability to function as potent inhibitors of oligosaccharide synthesis in eukaryotic cells has established them as unique biochemical probes of the role of glycosylation on protein structure and function. In this work, we describe a concise synthetic route to the tunicamycins, illustrated by the preparation of (+)-tunicamycin V (1-V).",10.1021/ja00058a060,1993-03-01,0.5785485738178172
Journal of the American Chemical Society,Establishing the Absolute Configuration of the Asbestinins:  Enantioselective Total Synthesis of 11-Acetoxy-4-deoxyasbestinin D,"A highly stereoselective synthesis of 11-acetoxy-4-deoxyasbestinin D (1) has been completed in 26 linear steps. The synthesis hinges on a selective glycolate aldol addition to establish the C-2 stereocenter, a ring-closing metathesis reaction to complete the oxonene, and an intramolecular Diels-Alder cycloaddition to establish the relative configuration at C-1, C-10, and C-14. This initial total synthesis of an asbestinin also serves to confirm the absolute configuration of this subclass of the C-2-C-11-cyclized cembranoid natural products.",10.1021/ja056921x,2005-11-15,0.5785452956593554
Tetrahedron,An efficient oxidative coupling method for synthesis of novel diastereomeric biaryl diols derived from estrone,,10.1016/j.tetlet.2012.11.109,2012-12-01,0.5785431261450177
Synthesis,Carbohydrate-Derived Bis(oxazoline) Ligand in the Total Synthesis of Grenadamide,"Using an optimised carbohydrate-based bis(oxazoline) ligand and copper(I) triflate, unactivated aliphatic alkenes were cyclopropanated­ with simple ethyl diazoacetate, giving the corresponding products in good yields and high stereoselectivities. The trans-disubstituted cyclopropyl carboxylic acid ester derived from 1-nonene was subsequently used as the key intermediate for the synthesis of the (+)-enantiomer of the natural product (-)-grenadamide. The efficient and high-yielding approach towards grenadamide reported here is the first to utilise asymmetric cyclopropanation for the construction of the chiral cyclopropyl unit.",10.1055/s-0030-1258143,2010-07-01,0.5785411251219276
Tetrahedron,New efficient synthetic routes to trifluoromethyl substituted pyrazoles and corresponding β-diketones,,10.1016/j.tetlet.2016.02.092,2016-02-28,0.578536860988177
Organic Letters,Enantioselective Access to Bicyclo[3.2.1]octadienone Skeleton: Total Syntheses of (+)-Engelharquinone and Its Epoxide,"The first enantioselective total syntheses of engelharquinone (2) and its epoxide 3 have been achieved. The key steps include (1) catalytic asymmetric 1,4-addition of a naphthylboronic acid derivative to a masked naphthoquinone derivative by using a chiral Rh-complex and (2) thiolate-promoted stereospecific construction of the bicyclo[3.2.1]octadienone scaffold.",10.1021/acs.orglett.7b00464,2017-03-01,0.5785361735073743
Synthesis,"A New Method for the Synthesis of 1,5-Disubstituted 1,2,3-Triazoles via Triazolium Salt Intermediates","A new transition metal free procedure for the synthesis of 1,5-disubstituted 1,2,3-triazoles, which proceeds via a triazolium salt intermediate is described.",10.1055/s-0032-1316806,2012-10-17,0.5785312928578963
Organic Letters,Synthesis of (±)-γ-Rubromycin via a New Hypoiodite-Catalytic Oxidative Cycloetherification,"A new synthesis of γ-rubromycin is presented through a new oxidative, bisbenzannulated spiroketalization as a key step which is catalyzed by an in situ generated hypoiodite species, developed previously by our group. This key transformation has high efficiency and convenient conditions. This is a new and efficient catalytic application for organohypoiodine reagents.",10.1021/ol3024874,2012-10-10,0.5785270377544594
Organic Letters,Total Synthesis of a Pyrroloindoloquinazoline Alkaloid,"A highly concise stereoselective synthesis of a newly identified alkaloid with a pyrroloindoloquinazoline skeleton has been achieved. To this end, a chiral auxiliary mediated asymmetric acetate aldol reaction on tryptanthrin was explored and the resulting adduct was converted to the product by a novel one-pot reductive cyclization/transamidation using NiCl2·6H2O/NaBH4 in methanol.",10.1021/ol401709t,2013-07-15,0.5785231012465828
Angewandte Chemie International Edition,"Divergent Total Synthesis of Four Kopsane Alkaloids: <i>N</i>‐Carbomethoxy‐10,22‐dioxokopsane, Epikopsanol‐10‐lactam, 10,22‐Dioxokopsane, and <i>N</i>‐Methylkopsanone","Abstract We have achieved the divergent total synthesis of four kopsane alkaloids which share a complex heptacyclic caged ring system. Key transformations include an asymmetric Diels–Alder reaction to assemble the central bicyclo[2.2.2]octane moiety and the quaternary stereocenter at C20, a SmI 2 ‐mediated cascade reduction/aldol reaction to construct the five‐membered ring and the quaternary stereocenter at C7, and a late‐stage cascade reductive amination/cyclization to establish the highly strained caged ring system.",10.1002/anie.202201712,2022-02-22,0.5785218996878744
Organic Letters,"Synthesis of Highly Oxidized Quinolizidine via Reduction of Acylpyridinium Cations, and Total Syntheses of Quinolizidines <b>207I</b> and 1-<i>epi</i>-<b>207I</b>","A new strategy for synthesizing quinolizidine skeletons by reductive cyclization via acylpyridinium cations was developed. Several functional groups, including carbonyl, silyl, and acetal, were tolerated under mild reaction conditions. The reaction was successfully extended to a one-pot synthesis of a bicyclic compound, and the synthetic strategy was applied to concise total syntheses of quinolizidines 207I and 1-epi-207I, without protecting groups.",10.1021/ol300541u,2012-03-22,0.5785202088641995
Organic Letters,"Efficient Access to 1,4-Benzothiazine: Palladium-Catalyzed Double C–S Bond Formation Using Na<sub>2</sub>S<sub>2</sub>O<sub>3</sub> as Sulfurating Reagent","A novel Pd-catalyzed double C-S bond formation coupling reaction has been developed. This protocol, in which Na2S2O3 was used as sulfurating reagent in metal-catalyzed reactions, provides an efficient method for the synthesis of substituted 1,4-benzothiazine derivates, which are structural elements of numerous bioactivity molecules rendering this protocol attractive to both synthetic and medicinal chemistry.",10.1021/ol400618k,2013-05-09,0.5785186084118025
Tetrahedron,Chemical synthesis and structural elucidation of a new serotonin metabolite: (4R)-2-[(5′-hydroxy-1′H-indol-3′-yl)methyl]thiazolidine-4-carboxylic acid,,10.1016/j.tetlet.2005.11.153,2005-12-22,0.578516333019377
Organic Process Research & Development,Pilot-Scale Synthesis and Purification of α-Asaronol for Antiepileptic Drug Development,"A simple and efficient pilot-scale process was developed for the synthesis and purification of α-asaronol (( E )-3′-hydroxyasarone). 4.29 kg of α-asaronol 4 (purity 99.92%) was produced in one batch, starting with 2,4,5-trimethoxybenzaldehyde 1 and ethyl hydrogen malonate 2 as raw materials to form intermediate ethyl ( E )-3-(2,4,5-trimethoxyphenyl)acrylate 3 (yield 93.3%) by the Knoevenagel condensation reaction, which was then reduced by diisobutylaluminum hydride to produce α-asaronol 4 with a yield of 89.2%. Liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) spectroscopy analysis revealed four major impurities in the synthesis process, namely, (2,4,5-trimethoxyphenyl)methanol, 3-(2,4,5-trimethoxyphenyl)propan-1-ol, 5,5′-((1 E,1′ E )-oxybis(prop-1-ene-3,1-diyl)) bis(1,2,4-trimethoxybenzene), and diethyl 2-(2,4,5-trimethoxybenzyl)malonate. By adapting a commonly used recrystallization process through optimization, a large-scale purification method was developed for the purification of α-asaronol, achieving a purity of 99.92% by recrystallization. The pilot study lays the groundwork for the large-scale, high-yield, and high-purity preparation of the candidate drug.",10.1021/acs.oprd.3c00076,2023-06-13,0.5785152425060935
Tetrahedron,Regioselective photocyloadditions of benzoquinones to alkylidenecyclohexanes: A new synthetic resource,,10.1016/s0040-4039(00)73621-5,1993-05-01,0.5785099140448444
Synlett,"An Asymmetric Synthesis of Muscarine, Suitable for the Elaboration of 5- Substituted Analogues","All articles of this category A total synthesis of (-)-Muscarine 11 has been achieved, starting from (S)-malic acid 4 , via the epoxy-ester 5 , and proceeding by way of an unusual cyclisation of the homoallylic alcohol 7 which gives the hydroxy-tetrahydrofuran 8a highly stereoselectively.",10.1055/s-1994-22835,1994-01-01,0.5785095078252532
Tetrahedron,"A convenient route to (+)-(9,11)-epithia-(11,12)-methano-thromboxane A2, from prostaglandin E2, methyl ester",,10.1016/s0040-4039(01)92486-4,1981-01-01,0.5785077135235733
Synlett,Stereoselective Synthesis of α-C-Galactopyranosides of Conduritols and Aminoconduritols,"All articles of this category Giese’s radical glycosidation of (-)-(1S,4R,5R,6R)-5- exo -(benzeneselenyl)-6- endo -chloro-3-methylidene-7-oxybicyclo[2.2.1]-heptan-2-one with tetra-O-acetylbromo-α-D-galactopyranose gave a C-galactoside that was converted into (+)-(1S,2R,3S,4R)-6-chloro-3- endo -[(2’,3’,4’,6’-tetra-O-acetyl-α-D-galactopyranosyl)methyl]-7-oxabicyclo[2.2.1]hept-5-en-2- endo -yl acetate ((+)- 6 ). Treatment of (+)- 6 with HBr, then with LiN 3 and subsequent reduction afforded (3S,4R,5R,6S)-3-amino-1-chloro-4-[(α-D-galactopyranosyl)methyl]-cyclohex-1-en-5,6-diol ((+)- 10 ). Acidic hydrolysis of (+)- 6 provided the (3R,4R,5R,6S)-1-chloro-4-[(α-D-galactopyranosyl)methyl]-cyclohex-1-en-3,5,6-triol derivative (+)- 11 or the (4R,5R,6S)-4-[(α-D-galactopyranosyl)methyl]-5,6-dihydroxycyclohex-2-en-1-one derivative (-)- 12 selectively. C-Glycosides - disaccharide mimics - 7-oxabicyclo[2.2.1]hept-2-enes - ”naked sugar” - 1-chlorocyclohex-2-enyl cations",10.1055/s-1996-5372,1996-03-01,0.5785056341021839
Organic Letters,Convergent and Stereospecific Synthesis of Highly Substituted Azepines,"This study reported a convergent pattern to stereospecifically synthesize 4,5-dihydrogen azepine from simple and readily available starting materials, addressing synthetic and stereoselective issues. Several synthetically important transformations, such as Simmon-Smith cyclopropanation, halogenation, and hydrogenation, demonstrated the utilities of this strategy. Particularly, the final azepine products could effectively contract into highly substituted pyridine derivatives through an intramolecular oxidation rearrangement.",10.1021/acs.orglett.4c03053,2024-09-16,0.5785043432502741
Organic Letters,Synthesis of Pyragonicin,"[structure: see text] A stereocontrolled convergent synthesis of the annonaceous acetogenin pyragonicin (1) is presented. The key intermediates were accessed using asymmetric Horner-Wadsworth-Emmons (HWE) methodology. A reagent controlled zinc-mediated stereoselective coupling, joining the two highly functionalized intermediates 3 and 4, then provided the core structure.",10.1021/ol050997g,2005-06-01,0.5784964347087178
Tetrahedron,"Paucidactine A and B, new indole alkaloids with a novel ring system containing a lactone moiety",,10.1016/0040-4039(96)00633-8,1996-05-01,0.5784951981428805
Angewandte Chemie International Edition,"A Fused [5]Helicene Dimer with a Figure‐Eight Topology: Synthesis, Chiral Resolution, and Electronic Properties","Abstract Chiral shape‐persistent molecular nanocarbons are promising chiroptical materials; their synthesis, however, remains a big challenge. Herein, we report the facile synthesis and chiral resolution of a double‐stranded figure‐eight carbon nanobelt 1 in which two [5]helicene units are fused together. Two synthetic routes were developed, and, in particular, a strategy involving Suzuki coupling‐mediated macrocyclization followed by Bi(OTf) 3 ‐catalyzed cyclization of vinyl ether turned out to be the most efficient. The structure of 1 was confirmed by X‐ray crystallographic analysis. The isolated ( P , P )‐ and ( M , M )‐ enantiomers show persistent chiroptical properties with relatively large dissymmetric factors (| g abs |=5.4×10 −3 and | g lum |=1.0×10 −2 ), which can be explained by the effective electron delocalization along the fully conjugated belt and the unique D 2 symmetry. 1 exhibits local aromatic character with a dominant structure containing eight Clar's aromatic sextet rings.",10.1002/anie.202302266,2023-04-03,0.5784911832985073
Journal of the American Chemical Society,Total Synthesis of Euonymine and Euonyminol Octaacetate,"Euonymine ( 1 ) and euonyminol octaacetate ( 2 ) share the core structure of euonyminol ( 3 ), the most hydroxylated member of the dihydro-β-agarofuran family. In 2, eight of the nine hydroxy groups of 3 are acetylated, and 1 has six acetyl groups and a 14-membered bislactone comprising a pyridine dicarboxylic acid with two methyl groups. The different acylation patterns provide distinct biological activities: 1 and 2 display anti-HIV and P-glycoprotein inhibitory effects, respectively. The 11 contiguous stereocenters and 9 oxygen functionalities of the ABC-ring system of 1 and 2 represent a formidable challenge, which is further heightened by the macrocyclic structure of 1 . Here we disclose an efficient synthetic strategy for enantioselective total synthesis of 1 and 2 . Starting from ( R )-glycerol acetonide, we constructed the B-ring by an Et 3 N-accelerated Diels–Alder reaction, the C-ring by intramolecular iodoetherification, and the A-ring by ring-closing olefin metathesis. The 10 stereocenters were installed through a series of substrate-controlled stereoselective C–C and C–O bond formations by exploiting the three-dimensional structures of judiciously designed substrates. These newly developed reaction sequences led to protected euonyminol 5, which served as a common intermediate for assembling 1 and 2 . Global deprotection of 5 and subsequent acetylation produced 2 . Alternatively, the discriminative protective groups of 5 allowed for site-selective bis-esterification to generate bislactone. Combining [3 + 2]-cycloaddition and reductive desulfurization introduced the last remaining stereocenters of the two methyl groups on the macrocycle. Finally, deprotection and acetylation gave rise to fully synthetic 1 for the first time.",10.1021/jacs.1c11038,2021-12-06,0.5784908276581016
Tetrahedron,Diastereospecific synthesis of diaziridines from D-mannitol. Access to chiral α-aminoacids.,,10.1016/s0040-4039(00)84935-7,1986-01-01,0.5784903141327752
Synlett,Application of Oxidative Ring Opening/Ring Closing by Reductive Amination Protocol for the Stereocontrolled Synthesis of Functionalized Azaheterocycles,Abstract The current Account gives an insight into the synthesis of some N-heterocyclic β-amino acid derivatives and various functionalized saturated azaheterocycles accessed from substituted cycloalkenes via ring C=C bond oxidative cleavage followed by ring closing across double reductive amination. The ring-cleavage protocol has been accomplished according to two common approaches: a) Os-catalyzed dihydroxylation/NaIO4 vicinal diol oxidation and b) ozonolysis. A comparative study on these methodologies has been investigated. Due to the everincreasing relevance of organofluorine chemistry in drug research as well as of the high biological potential of β-amino acid derivatives several illustrative examples to the access of various fluorine-containing piperidine or azepane β-amino acid derivatives are also presented in the current Account. 1 Introduction 2 Olefin-Bond Transformation by Oxidative Ring Cleavage 3 Synthesis of Saturated Azaheterocycles via Oxidative Ring-Opening/Ring-Closing Double Reductive Amination 3.1 Importance of Fluorine-Containing Azaheterocycles in Pharmaceutical Research 3.2 Synthesis of Azaheterocyclic Amino Acid Derivatives with a Piperidine or Azepane Framework through Oxidative Ring Opening/Reductive Amination 3.2.1 Synthesis of Piperidine β-Amino Esters 3.2.2 Synthesis of Azepane β-Amino Esters 3.2.3 Synthesis of Fluorine-Containing Piperidine γ-Amino Esters 3.3 Synthesis of Tetrahydroisoquinoline Derivatives through Oxidative Ring Opening/Reductive Amination Protocol 3.4 Synthesis of Functionalized Benzazepines through Reductive Amination 3.4.1 Synthesis of Benzo[c]azepines 3.4.2 Synthesis of Benzo[d]azepines 3.5 Synthesis of Various N-Heterocycles via Ozonolysis/Reductive Amination 3.5.1 Synthesis of Compounds with an Azepane Ring 3.5.2 Synthesis of Piperidine β-Amino Acids and Piperidine-Fused β-Lactams 3.5.3 Synthesis of γ-Lactams with a Piperidine Ring 3.5.4 Synthesis of other N-Heterocycles 4 Summary and Outlook 5 List of Abbreviations,10.1055/s-0040-1719850,2021-11-03,0.5784894742578292
Journal of Organic Chemistry,Copper-Catalyzed Cascade Amination Route to <i>N</i>-Aryl Benzimidazoquinazolinones,An efficient one-pot Cu-catalyzed C-H functionalization/two-fold C-N bond formation protocol for the syntheses of N-aryl benzimidazoquinazolinones is being reported. This strategy involves a Cu-catalyzed C-N bond coupling reaction between N-anilinoquinazolinones and aryl/heteroaryl halides followed by acetate ligand-assisted intramolecular C-H amination.a This reaction is high-yielding and straightforward for the synthesis of anti-cancer drug analogues of benzimidazoquinazolinones.,10.1021/acs.joc.6b01287,2016-08-12,0.5784884266018419
Tetrahedron,"PhenylsulfenylD-ribofuranosides as efficient ribosyl donors: Application to the synthesis of [1′,-13C]-(deoxy)nucleosides",,10.1016/s0040-4039(00)79089-7,1992-09-01,0.5784874242958539
Synlett,Efficient Synthesis of N-(9-Xanthyl)-4-Toluenesulfonamides Enabled by an Addition-Cyclization Cascade of Arynes,An efficient synthesis of N -(9-xanthyl)-4-toluenesulfonamides is described in which salicyl N -tosylimines react with silyl­aryl triflates in the presence of CsF. This mild process involves an addition–cyclization cascade in which arynes are generated and trapped in situ.,10.1055/s-0032-1318311,2013-02-20,0.5784862902804011
European Journal of Organic Chemistry,Towards the Total Synthesis of Pamamycin-607: Preparation of the Eastern Part (C8–C18 Fragment),,10.1002/(sici)1099-0690(199909)1999:9<2303::aid-ejoc2303>3.3.co;2-#,1999-09-01,0.5784833435201885
Tetrahedron,Toward the total synthesis of Scleritodermin A: preparation of the C1–N15 fragment,,10.1016/j.tetlet.2007.01.034,2007-01-11,0.5784833435201885
Synthesis,"A Remarkably Efficient and Direct Route for the Synthesis of Binucleating 1,4,7-Triazacyclononane Ligands","An extremely efficient and direct route towards a range of binucleating analogues of 1,4,7-triazacyclononane 5a-f, has been developed. In all cases the reactions of benzylic and aliphatic diamines with ditosylate ester 3 proceed to give the target binucleating ligands almost exclusively and in excellent yield.",10.1055/s-2001-18706,2002-07-26,0.5784799440952464
Organic Letters,Two-Step Synthesis of α-Aryl-α-diazoamides as Modular Bioreversible Labels,"α-Aryl-α-diazoamides were synthesized in two steps under mild conditions. This expeditious route employs Pd-catalyzed C–H arylation of N -succinimidyl 2-diazoacetate to obtain N -succinimidyl 2-aryl-2-diazoacetates, followed by aminolysis. The ensuing diazo compounds can esterify carboxyl groups in aqueous solution, and the ester products are substrates for an esterase. The broad scope of the synthetic route enables the continued development of diazo compounds in chemical biology.",10.1021/acs.orglett.1c00793,2021-04-05,0.5784765367564318
Organic Letters,Convergent Strategy for the Regioselective Synthesis of Nonaggregated α-Triaryl-β-carboxy Zinc Phthalocyanines,A new design of nonaggregated zinc(II) carboxyphthalocyanines with potential application in dye-sensitized solar cells has been developed. It is based on the introduction of bulky and rigid aryl groups at three α positions of the macrocycle. The synthesis has been carried out following a convergent route in which the bulky aryl groups are introduced by a Suzuki-Miyaura cross-coupling reaction on a preformed triiodophthalocyanine derivative. Two regioisomers of this α-triaryl-β-carboxyphthalocyanine could be isolated by column chromatography.,10.1021/ol503557c,2015-01-20,0.5784729676182165
Journal of Organic Chemistry,Total Synthesis and Biological Evaluation of an Antifungal Tricyclic <i>o</i>-Hydroxy-<i>p</i>-Quinone Methide Diterpenoid,"A convergent route has been developed to synthesize an antifungal tricyclic o-hydroxy-p-quinone methide diterpenoid and analogues. A Li/naphthalene-mediated reductive alkylation was employed for coupling β-cyclocitral and the corresponding benzyl chloride, while a BBr3-mediated one-pot bis-demethylation and intramolecular Friedel-Crafts alkylation was used to assemble the tricyclic molecular skeleton. The structure-activity relationship of the diterpenoid was assessed on the basis of antiproliferation assays of the natural product and analogues against strains of pathogenic yeasts and filamentous fungi.",10.1021/jo4013964,2013-08-19,0.5784726288837525
Journal of Organic Chemistry,"Synthetic Studies toward GKK1032s, Novel Antibiotic Antitumor Agents:  Enantioselective Synthesis of the Fully Elaborated Tricyclic Core via an Intramolecular Diels−Alder Cycloaddition","An enantioselective synthesis of the fully elaborated tricyclic decahydrofluorene core (ABC-ring system) of GKK1032s, novel antimicrobial and antitumor agents, has been accomplished for the first time by employing a highly diastereoselective intramolecular Diels-Alder (IMDA) reaction. The key substrate for the IMDA reaction was efficiently prepared through (i) an intermolecular Diels-Alder reaction between a siloxydiene and an optically active enone derived from D-mannitol to construct the appropriately functionalized C-ring and (ii) CuCl-promoted Stille coupling of an (E)-vinyl iodide and a vinylstannane to install the requisite triene side chain as the crucial steps.",10.1021/jo0610208,2006-08-05,0.5784665354694442
Organic Letters,Total Synthesis and Structure Assignment of Saptomycin H,"High Resolution Image Download MS PowerPoint Slide We report herein the first total synthesis of saptomycin H ( 2 ), by which the unidentified absolute stereochemistry of the oxiranyl side chain has been determined as 14 R,16 S . The keys include (1) concise assembly of three units, anthrone, sugar and side chain, and (2) AZADOL-mediated 6- endo -selective pyranone (A-ring) formation.",10.1021/acs.orglett.1c04306,2022-02-11,0.5784652181554831
Tetrahedron,"Studies of novel cyclitols. A synthesis of 3′O,4′O-dimethylfuniculosin",,10.1016/s0040-4039(00)01496-9,2000-12-01,0.5784534074767604
Tetrahedron,Synthesis and binding studies of novel bisthiacalix[4]arenes with diimime linkages,,10.1016/j.tetlet.2004.11.008,2004-12-06,0.5784534074767604
European Journal of Organic Chemistry,Total Synthesis of the Isoketal 5‐D<sub>2</sub>‐IsoK Natural Product Based on Organocatalysis,"The enantioselective total synthesis of the highly reactive isoketal 5‐D 2 ‐IsoK was accomplished. The synthesis involved construction of the isoketal core by an organocatalyzed Michael addition between ideally functionalized aldehyde and nitroolefin partners with good enantioselectivity. The lateral chains were branched through Horner–Wadsworth‐Emmons and Wittig olefinations to provide flexibility, whereas the final deprotection and oxidation steps were performed under mild conditions to avoid known racemization and/or degradation of the very sensitive isoketal.",10.1002/ejoc.201601301,2016-10-21,0.5784519384149793
Tetrahedron,A new and novel approach towards the synthesis of 3′-deoxy-3′-hydroxymethyl ribofuosides,,10.1016/s0040-4039(00)94705-1,1990-01-01,0.5784488183431726
Organic Process Research & Development,A Practical Synthesis of (<i>R</i>)-(−)-Phenylephrine Hydrochloride,"( R )-(−)-Phenylephrine hydrochloride is a clinically potent adrenergic agent and β-receptor sympathomimetic drug, exclusively marketed in the optically active form. An asymmetric synthesis has been developed with high enantiomeric excess based on hydrolytic kinetic resolution of a styrene oxide derivative using ( R,R )-SalenCo III OAc complex.",10.1021/op970128+,1998-09-30,0.5784435559691746
Journal of Organic Chemistry,Studies toward the Total Synthesis of Dumsin. 2. A Second Generation Approach Resulting in Enantioselective Construction of a Functionalized ABC Subunit of the Tetranortriterpenoid Insect Antifeedant,"A synthesis of the ABC framework of dumsin is described. The optically active intermediate 9b, which is expeditiously assembled from 5-oxobornyl pivalate by the sequential implementation of an oxy-Cope rearrangement and an intramolecular ene reaction, proved to be suitably functionalized for ultimate conversion to 5. The synthesis plan relies on two approaches to this targeted intermediate. In the first, the exocyclic double bond introduced during EtAlCl2-promoted closure of aldehyde 10b is cleaved to leave a carbonyl group that is amenable to hydride reduction and elimination of water. Cleavage of the resulting double bond with ruthenium tetroxide provided the seco ketoacid. The same advanced intermediate was obtained by initially positioning the double bond internal to the five-membered ring in advance of transient ring expansion via diketone formation and intramolecular aldolization. Both of these approaches bypass the complications arising from the substantial steric congestion prevailing in these structural networks. The task of covalently positioning an oxygen atom adjacent to the gem-dimethyl-substituted carbon in 5 was properly realized by oxidative decarboxylation. The stereochemical assignments to many of the intermediates were confirmed by an X-ray crystallographic analysis of 43.",10.1021/jo062068o,2006-12-07,0.5784416763282073
Journal of Organic Chemistry,"Catalytic Route to the Synthesis of Optically Active β,β-Difluoroglutamic Acid and β,β-Difluoroproline Derivatives","Beta,beta-difluorinated amino acid derivatives were synthesized via Mg(0)-promoted defluorination of alpha-trifluoromethyl iminoester. Bromination of the difluoroenamine afforded the bromodifluoromethyl iminoester in good yield. Pd-catalyzed asymmetric hydrogenation of the bromodifluoromethyl iminoester and the subsequent transformations provided optically active beta,beta-difluoroglutamic acid and beta,beta-difluoroproline derivatives.",10.1021/jo049789c,2004-06-22,0.5784388538337681
Chemical Science,Chemo- and atroposelective Boc protection for asymmetric synthesis of NH <sub>2</sub> -free axially chiral biaryl amino phenols,The first Lewis base-catalyzed enantioselective tert -butoxycarbonyl (Boc) protection strategy has been developed for the construction of NH 2 -free axially chiral biaryl amino phenols.,10.1039/d5sc06233k,2025-01-01,0.5784304264620197
Synlett,"Transition Metal Complexes in Organic Synthesis, Part 69.Total Synthesis of the<i>Amaryllidaceae</i>Alkaloids Anhydrolycorinone and Hippadine Using Iron- and Palladium-Mediated Coupling Reactions",A novel synthesis of the Amaryllidaceae alkaloids anhydrolycorinone and hippadine has been developed using an iron-mediated oxidative alkylamine cyclization and an intramolecular palladium-mediated biaryl coupling as the key steps.,10.1055/s-2003-41438,2003-01-01,0.5784246789942752
Synthesis,An Approach to the Synthesis of Pyrimido[b]azepines via Ruthenium-Catalyzed Ring-Closing Metathesis,"A highly efficient approach to the synthesis of a series of pyrimido[ b ]azepines has been developed with 5-allyl-2,4,6-trichloropyrimidine as the starting material in six or seven steps via a ring-closing metathesis (RCM) reaction. The absolute configuration of the key intermediate pyrimido[4,5- b ]azepine was ascertained by X-ray crystal structure analysis.",10.1055/s-0034-1381009,2015-07-24,0.578424006791256
Journal of Organic Chemistry,"Silver-Mediated [2 + 2 + 1] Cyclization of <i>ortho</i>-Propioloylbenzonitriles with Elemental Selenium: Synthesis of 4<i>H</i>-indeno[1,2-<i>c</i>][1,2]selenazol-4-ones","An efficient silver-mediated [2 + 2 + 1] cyclization protocol of ortho -propioloylbenzonitriles with elemental selenium for the synthesis of 4 H -indeno[1,2- c ][1,2]selenazol-4-ones has been developed. One C–Se bond, one N–Se bond, and one C–C bond were rapidly constructed in one step. The reaction might proceed via the formation of a highly reactive selenoketene intermediate, followed by intramolecular cyclization.",10.1021/acs.joc.3c01172,2023-08-30,0.578423668548001
Angewandte Chemie International Edition,"Synthesis of Tetrazino‐tetrazine 1,3,6,8‐Tetraoxide (TTTO)","This study presents the first synthesis and characterization of a new high energy compound [1,2,3,4]tetrazino[5,6-e][1,2,3,4]tetrazine 1,3,6,8-tetraoxide (TTTO). It was synthesized in ten steps from 2,2-bis(tert-butyl-NNO-azoxy)acetonitrile. The synthetic strategy was based on the sequential closure of two 1,2,3,4-tetrazine 1,3-dioxide rings by the generation of oxodiazonium ions and their intramolecular coupling with tert-butyl-NNO-azoxy groups. The TTTO structure was confirmed by single-crystal X-ray.",10.1002/anie.201605611,2016-07-20,0.5784215404776327
Journal of the American Chemical Society,"Versatile Construction of 6-Substituted <i>cis</i>-2,8-Dioxabicyclo[3.3.0]octan-3-ones: Short Enantioselective Total Syntheses of Cheloviolenes A and B and Dendrillolide C","A short enantioselective synthesis of 6-substituted cis-2,8-dioxabicyclo[3.3.0]octan-3-ones is described. The pivotal step is coupling of a tertiary radical generated directly from a tertiary alcohol with a 3-chloro-5-alkoxybutenolide. This strategy is applied toward scalable 14-15 step syntheses of three rearranged spongian diterpenoids: cheloviolenes A and B and dendrillolide C.",10.1021/jacs.7b04265,2017-05-17,0.5784203119481586
European Journal of Organic Chemistry,Synthesis of Fullerene‐Stoppered Rotaxanes Bearing Ferrocene Groups on the Macrocycle,"Abstract The synthesis, characterisation and behaviour of a series of rotaxanes containing a fulleropyrrolidine stopper and two ferrocene moieties on the macrocycle is reported. Remarkably, the presence of large and bulky ferrocene groups does not interfere either in the synthesis or in the translocation of the macrocycle induced by π–π interactions between the macrocycle and the fullerene. The synthetic routes developed can also be applied to the preparation of rotaxane scaffolds that can be complexed to [Ru(CO)TPP] by axial coordination. Overall, the synthetic routes presented herein provide an efficient way to prepare a variety of rotaxanes and molecular shuttles with potential applications in different fields.",10.1002/ejoc.200901309,2010-01-19,0.5784165691113646
Synthesis,Recent Advances in the Synthesis and Application of Benzocyclobutenones and Related Compounds,"Benzocyclobutenones are an intriguing class of four-membered-ring ketones that have been used extensively as powerful synthetic intermediates in organic synthesis. Their high reactivity is primarily attributed to the unique high electrophilicity of the carbonyl unit and the ability to generate o -quinone dimethides, allowing a myriad of different transformations. However, the synthesis of benzocyclobutenones still represents a great challenge. This review provides an overview of the preparation, use and impact of benzocyclobutenones in organic synthesis. Selected applications in the synthesis of natural products are also described, in order to illustrate the utility of these compounds. 1 Introduction 2 Synthetic Methods for Preparing Benzocyclobutenones 2.1 [2+2]-Type Cycloadditions 2.2 Metal-Mediated Intramolecular Cyclizations 2.3 Metal-Catalyzed Cross-Coupling Reactions 2.3.1 Carbon–Hydrogen Bond-Functionalization Events 2.3.2 Stille Cross-Coupling Reactions 2.4 Other Synthetic Methods for Preparing Benzocyclobutenones 3 Synthetic Application of Benzocyclobutenones and Related Compounds 3.1 Synthesis of Polycyclic Compounds via o -Quinone Dimethides 3.1.1 Synthesis of α-Tetralones 3.1.2 Synthesis of Benzo[n]annulenes 3.1.3 Synthesis of Naphthalene Derivatives 3.1.4 Synthesis of Anthraquinones 3.1.5 Synthesis of Benzodiazepines 3.1.6 Synthesis of Tetrahydronaphthalenes 3.1.7 Synthesis of Isochromanones 3.2 Synthesis of Fused Rings via Non-Electrocyclization Techniques 3.2.1 Ring Expansions from Four- to Five-Membered Rings 3.2.2 Ring Expansions from Four- to Six-Membered Rings 3.3 Other Synthetic Applications 3.3.1 Tricarbonylchromium Complexes 3.3.2 Base-Induced Carbon–Carbon Bond Cleavage 3.4 Benzocyclobutenones and Their Derivatives in Natural Product Synthesis 4 Conclusions",10.1055/s-0032-1316850,2013-02-12,0.5784140189714844
European Journal of Organic Chemistry,"One‐Pot Synthesis of 3‐Aryl‐5‐amino‐1,2,4‐thiadiazoles from Imidates and Thioureas by I<sub>2</sub>‐Mediated Oxidative Construction of the N–S Bond","A simple and practical method for the one‐pot synthesis of 3‐aryl‐5‐amino‐1,2,4‐thiadiazoles from imidates and thioureas has been developed. The protocol proceeds through sequential base‐mediated nucleophilic addition‐elimination reactions and an I 2 ‐mediated oxidative coupling for the N–S bond formation. The approach employes readily available and nontoxic substrates and a simple workup to provide 3‐aryl‐5‐amino‐1,2,4‐thiadiazoles that have a free or substituted amino group.",10.1002/ejoc.201800670,2018-06-05,0.5784132175928791
Organic Letters,"Organocatalytically Generated Donor–Acceptor Cyclopropanes in Domino Reactions. One-Step Enantioselective Synthesis of Pyrrolo[1,2-<i>a</i>]quinolines","An easy and straightforward procedure has been developed for the synthesis of highly enantioenriched pyrrolo[1,2-a]quinolines through a one-pot process that comprises a domino cyclopropane ring opening/aza-Michael/aldol reaction followed by acid-promoted lactamization. The key feature of the synthetic approach relies on the ability of conveniently functionalized cyclopropaneacetaldehydes to undergo organocatalytic activation by a chiral secondary amine that enables the catalytic generation of a donor-acceptor cyclopropane. This intermediate has the potential to undergo a ring opening that generates an electrophilic α,β-unsaturated iminium ion that subsequently reacts through the already mentioned domino sequence and in which stereochemical information is very efficiently transferred from the amine catalyst to the final products. Moreover, one of the alkoxycarbonyl moieties can be easily removed by standard hydrolysis/decarboxylation, providing access to the target adducts as single stereoisomers.",10.1021/acs.orglett.6b00173,2016-02-26,0.5784131343376014
European Journal of Organic Chemistry,A Formal Total Synthesis of Salvadione,"Abstract The tricyclic 6‐7‐6 core structure of the triterpene salvadione ( 1 ) was obtained in an efficient manner from the aryl bromide 16 and the alkyl iodide 35 carrying a methylenecyclohexane group at the terminus. Alkylation of the anion derived from 16 with the iodide 35 gave the tethered system 36 . This compound was converted into the allylic bromide 40 . Finally, a Lewis acid mediated intramolecular Friedel–Crafts alkylation furnished the target structure 13 in good overall yield. The synthesis of tricyclic compound 13 represents a formal total synthesis of salvadione ( 1 ). (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2006)",10.1002/ejoc.200600361,2006-06-30,0.5784084770147168
Angewandte Chemie International Edition,Gold‐Catalyzed Asymmetric Intramolecular Cyclization of N‐Allenamides for the Synthesis of Chiral Tetrahydrocarbolines,"Abstract Highly enantioselective gold‐catalyzed intramolecular cyclization of N‐allenamides was implemented by utilizing a designed chiral sulfinamide phosphine ligand (PC‐Phos). This represents the first example of highly enantioselective intramolecular cyclization of N‐allenamides. The practicality of this reaction was validated in the total synthesis of ( R )‐desbromoarborescidine A and formal synthesis of ( R )‐desbromoarborescidine C and ( R )‐deplancheine. Moreover, the catalyst system PC‐Phos/AuNTf 2 proved to be specifically efficient to promote the desymmetrization of N‐allenamides in excellent yields with satisfactory ee values.",10.1002/anie.201709595,2017-10-28,0.5784075148257624
Synthesis,Synthesis of 1-Oxo-1-(3-pyridazinyl) Derivatives - Potent Inhibitors of Fatty Acid Amide Hydrolase (FAAH): An Improved and Optimized Procedure,"A greatly improved procedure for the preparation of long-chain &#945;-ketopyridazines, a class of potent inhibitors of fatty acid amide hydrolase (FAAH), is described. This optimization study shows a great dependence of the yields of desired products on the pyrididazinyl lithium/Weinreb amide ratio and offers a general approach to this kind of compound.",10.1055/s-2007-990774,2007-09-24,0.5783997604874235
Tetrahedron,A new synthesis of cyanocyclopropanes by the intramolecular alkylation of magnesium carbenoids as the key reaction,,10.1016/j.tetlet.2010.04.090,2010-04-29,0.5783947761113949
Journal of the American Chemical Society,Total Synthesis of the Lycorenine-Type Amaryllidaceae Alkaloid (±)-Clivonine via a Biomimetic Ring-Switch from a Lycorine-Type Progenitor,"A fully diastereoselective total synthesis of the lycorenine-type Amaryllidaceae alkaloid (+/-)-clivonine (19) is reported via a route that employs for the first time a biomimetic ring-switch from a lycorine-type progenitor, thereby corroborating experimentally the biogenetic hypothesis first expounded for these compounds by Barton in 1960.",10.1021/ja910184j,2010-03-17,0.5783922777173167
Organic Letters,Stereocontrolled Synthesis of (+)-Boronolide,Boronolide was synthesized stereoselectively from hydroxyacetylfuran 5 and valeraldehyde 6 using a novel dizinc aldol catalyst. Ring closing metathesis provides the lactone ring. The synthesis requires 12 steps and proceeds in 26% overall yield. [reaction: see text],10.1021/ol026665i,2002-09-05,0.5783876877285
Journal of Organic Chemistry,Selective Synthesis of Either Enantiomer of α-Amino Acids by Switching the Regiochemistry of the Tricyclic Iminolactones Prepared from a Single Chiral Source,Preparation of l-alpha-amino acids was easily accomplished simply by exchanging the position of the lactone group of our recently reported chiral template 1 from C2 to C3. The new chiral template 7 was prepared in 54% overall yield over five steps from (1R)-(+)-camphor. Alkylation of iminolactone 7 afforded the alpha-monosubstituted products in good yields and excellent diastereoselectivities (>98%). Hydrolysis of the alkylated iminolactones furnished the desired l-alpha-amino acids in good yields and ee with nearly quantitative recovery of chiral auxiliary 4.,10.1021/jo026285a,2002-12-31,0.5783809822981487
Organic Letters,Synthesis of (−)-Monanchoradin A and (−)-Crambescin A2 392 Based on a Cyclization–Carbonylation–Cyclization Cascade,Syntheses of guanidino alkaloids (-)-monanchoradin A and (-)-crambescin A2 392 are described. The key feature of the syntheses is the cyclization-carbonylation-cyclization cascade of the optically active propargyl guanidine. The bicyclic guanidino cores bearing an asymmetric center and ester or carboxylic acid functionality were constructed in a single step. The carboxylic acid was then converted to (-)-monanchoradin A and (-)-crambescin A2 392.,10.1021/acs.orglett.4c03158,2024-10-14,0.578379250872395
Tetrahedron,"A novel method for stereoselective synthesis of (1R,2R)-diarylethylenediamines by reductive intramolecular coupling of aromatic diimines",,10.1016/s0040-4039(00)61145-0,1992-09-01,0.5783729770931129
Organic Letters,Remote C–H Activation Strategy Enables Total Syntheses of Nortriterpenoids (±)-Walsucochin B and (±)-Walsucochinoids M and N,"Total syntheses of (±)-walsucochin B and (±)-walsucochinoids M and N have been achieved from farnesyl bromide. The key steps of the synthetic sequence are the titanocene-mediated radical cyclization and base-induced cycloaromatization for the rapid construction of the 6/6/5/6-fused tetracyclic skeleton. Importantly, a Cu-mediated remote C-H hydroxylation reaction has been developed to site-selectively install the oxygen function at the C-7 position of the target molecules, thus solving the biggest challenge for the synthesis of the compounds.",10.1021/acs.orglett.0c02548,2020-08-21,0.5783721920050672
Tetrahedron,"Indolocarbazoles. 2. Synthetic studies towards staurosporine. An unexpected 1,2 migration of indolocarbazole nitrogen results in a novel and potent Protein kinase C inhibitor.",,10.1016/s0040-4039(00)73833-0,1993-09-01,0.5783706372854222
Tetrahedron,High yield selective 3′-silylation of ribonucleosides,,10.1016/s0040-4039(01)92470-0,1981-01-01,0.5783677127553374
Chemical Science,Spatiotemporally controlled O <sub>2</sub> and singlet oxygen self-sufficient nanophotosensitizers enable the <i>in vivo</i> high-yield synthesis of drugs and efficient hypoxic tumor therapy,"A porous photosensitizer displaying catalase-like activity and drug synthesis ability was synthesized for the synergistic chemo-photodynamic therapy, opening new promising ways for carrying out the precise cooperative treatment of hypoxic tumors.",10.1039/d0sc02387f,2020-01-01,0.5783658001779041
Organic Letters,Cycloaldol Approach to the Isobenzofuran Core of Eunicellin Diterpenes,[reaction: see text] A novel cycloaldol approach to the isobenzofuran core common to many of the eunicellin diterpenes is described. The cycloaldol precursor was prepared by aldol addition of (S)-(+)-carvone and methacrolein followed by etherification to a glycolate ester. Chemoselective enolization of the glycolate ester led to the cycloaldol adduct in high yield and diastereoselectivity. An oxidative rearrangement-allylic diazene rearrangement sequence established the requisite cis ring fusion.,10.1021/ol034052f,2003-03-07,0.57835887933318
European Journal of Organic Chemistry,Synthesis of 2‐Substituted Thioglycals from Carbohydrate‐Derived Ketene Dithioacetals,A novel strategy for the synthesis of 2‐substituted thioglycals has been developed from a carbohydrate‐derived ketene dithioacetal in a two‐step sequence. The introduction of various electrophilic groups at the double bond of the ketene dithioacetal was achieved before the elimination of the thioalkyl group to yield 2‐substituted thioglycals. Removal of the exocyclic thioalkyl group was obtained by the selective formation of the exocyclic glycosyl sulfoxide followed by treatment by an organolithium reagent. The synthetic potential of these 2‐substituted thioglycals was illustrated by the alkylation at the sulfur atom leading to unsaturated carbohydrate‐derived sulfonium salts.,10.1002/ejoc.202000312,2020-04-07,0.5783571468858447
Synlett,"Asymmetric Synthesis of (1S,2R)-1-Amino-2-methylcyclopropanephosphonic Acid: A Phosphonic Analogue of (–)-Norcoronamic Acid – Influence of Stereochemistry on Regioselectivity in Sulfoxide–Metal Exchange","Asymmetric synthesis of (–)-(1 S ,2 R )-1-amino-2-methylcyclopropanephosphonic acid, a phosphonic analogue of (–)-norcoronamic acid was developed. The presence of the nitrile group as a precursor of the amino moiety, by changing stereoselectivity in the alkylation step, in consequence allowed to avoid 1,2-migration of a phosphoryl group on the cyclopropane ring and to obtain the required cyclopropylphosphonate of the retained structure and configuration.",10.1055/s-0034-1378538,2014-08-06,0.578345297944232
Tetrahedron,Methyl α-acyloxy-γ-methylene-β-tetronate. Preparation and use as a building block for the synthesis of the spirotetronic acid structure of chlorothricolide,,10.1016/s0040-4039(00)99656-4,1989-01-01,0.5783403883787979
Tetrahedron,The first chemo- and regiospecific palladium-catalyzed enyne-diyne [4+2] intermolecular cross-benzannulation: an effective route to polysubstituted benzenes,,10.1016/s0040-4039(97)10295-7,1997-12-01,0.5783383570812681
Tetrahedron,"Asymmetric synthesis. XLI. Totally stereoselective synthesis of 1,3-disubstituted tetrahydroisoquinolines via the CN(R,S) method",,10.1016/0040-4039(96)00819-2,1996-06-01,0.5783382541226917
Organic Letters,Palladium-Catalyzed Asymmetric Synthesis of Axially Chiral Allenylsilanes and Their Application to S<sub>E</sub>2′ Chirality Transfer Reactions,"Stepwise application of the Pd-catalyzed S(N)2' reaction and the desilylative S(E)2' reaction to the ambivalent 2-bromo-1-silyl-1,3-dienes provides a novel route to the highly enantioselective construction of tertiary and quaternary propargylic stereogenic centers via axially chiral allenylsilanes.",10.1021/ol102554a,2010-11-19,0.5783328877370546
Journal of the American Chemical Society,11-Step Total Synthesis of Teleocidins B-1–B-4,"A unified and modular approach to the teleocidin B family of natural products is presented that proceeds in 11 steps and features an array of interesting strategies and methods. Indolactam V, the known biosynthetic precursor to this family, was accessed through electrochemical amination, Cu-mediated aziridine opening, and a remarkable base-induced macrolactamization. Guided by a desire to minimize concession steps, the tactical combination of C-H borylation and a Sigman-Heck transform enabled the convergent, stereocontrolled synthesis of the teleocidins.",10.1021/jacs.8b13697,2019-01-13,0.5783291244271022
Organic Process Research & Development,Access to Phenolic Pyridopyridazinones and Phthalazinones Using THP Ether-Directed Ortho Lithiation,"Route scouting, process research and development, and large-scale synthesis of phenol-substituted pyridopyridazinones (azaphthalazinones) and phthalazinones are reported. For the introduction of one of our key building blocks, 3-(trifluoromethyl)phenol, our identified large-scale route initially employed an unstable aryllithium, generated by bromine lithium exchange next to a phenolic hydroxy group protected as p -methoxybenzyl (PMB) ether. We found that instead, protecting the phenolic hydroxy group as tetrahydropyran (THP) ether in a bromine-free substrate and applying directed ortho metalation (DoM) generated the desired aryllithium in a stable form, suitable for use in a batch process on a large scale, which significantly facilitated the synthesis of our target molecules. The final process, a palladium-free, telescoped two-step sequence consisting of ketone formation by acylation with a mixed diester and cyclization with hydrazine, was demonstrated in our kilogram laboratory on a 0.5 kg scale for the pyridopyridazinone scaffold. Routes to the analogous phthalazinone scaffold were also investigated, and here, both phthalic anhydride and a mixed diester can serve as starting material. DFT calculations support our rationale regarding experimentally found differences between pyridine- and benzene-based intermediates. The target molecules were isolated as crystalline solids, and their structures were further confirmed by single crystal X-ray diffraction.",10.1021/acs.oprd.4c00541,2025-04-15,0.5783281213499497
Journal of the American Chemical Society,Total Synthesis of Daptomycin by Cyclization via a Chemoselective Serine Ligation,"A total synthesis of daptomycin, the first natural product antibiotic launched in a generation, was achieved. This convergent synthesis relies on an efficient macrocyclization via a serine ligation to assemble the 31-membered cyclic depsipeptide. The difficult esterification by the nonproteinogenic amino acid kynurenine was accomplished via the esterification of a threonine residue by a suitably protected Trp ester, followed by ozonolysis. This synthesis provides a foundation and framework to prepare varied analogues of daptomycin to establish its structure-activity profile.",10.1021/ja4012468,2013-04-05,0.5783253240859206
Synthesis,A Domino Heck Coupling–Cyclization–Dehydrogenative Strategy for the One-Pot Synthesis of Quinolines,"Abstract An efficient, one-pot, domino synthesis of quinolines via the coupling of iodoanilines with allylic alcohols facilitated by palladium catalysis is described. The overall synthetic process involves an intermolecular Heck coupling between 2-iodoanilines and allylic alcohols, intramolecular condensation of in situ generated ketones with an internal amine functional group, and a dehydrogenation sequence. Notably, this protocol occurs in water as a green solvent. Significantly, the method exhibits broad substrate scope and is applied for the synthesis of deuterated quinolines through a deuterium-exchange process.",10.1055/a-1589-7548,2021-08-17,0.5783173186752661
Organic Letters,Stereospecific Synthesis of Cyclobutanones and Spirohexanones via Formal [3 + 1] Cycloaddition of Cyclopropanones with Sulfur Ylides,"A concise synthetic route to enantioenriched cyclobutanones is reported via ring expansion of cyclopropanone surrogates with unstabilized sulfoxonium ylides. The reaction is shown to proceed with complete regio- and stereospecificity with chiral substrates, leading to optically active 2,3-disubstituted cyclobutanones where reversible enamine formation allowed for controlled equilibration to the thermodynamic trans diastereomer. Alternatively, employing Trost’s cyclopropylsulfonium reagent provided the first synthesis of enantioenriched spiro[2.3]hexan-4-ones via a unique semipinacol rearrangement of a dicyclopropyl betaine intermediate.",10.1021/acs.orglett.5c02601,2025-07-22,0.578312793664472
Tetrahedron,"1,4-diene and 1,4-enyne synthesis via dichloronorcarenol cleavage.Synthesis of crepenynic acid.",,10.1016/s0040-4039(01)95181-0,1978-01-01,0.5783125281624996
Organic Letters,Synthesis of Substituted Indoline and Carbazole by Benzyne-Mediated Cyclization–Functionalization,"A benzyne-mediated synthesis of substituted indolines and carbazoles was developed. The reaction includes generation of benzyne using Mg(TMP)2·2LiCl as a base, cyclization, and trapping the resulting organomagnesium intermediate with an electrophile to provide a series of substituted indolines and carbazoles in a regiospecific manner. This was applied to a concise five-pot total synthesis of heptaphylline.",10.1021/ol400597f,2013-04-02,0.5783054537489987
Tetrahedron,"An efficient synthesis of 2-(3-(4-amidinophenylcarbamoyl)naphthalen-2-yl)-5-((2,2-methylpropyl)carbamoyl)benzoic acid: a factor VIIa inhibitor discovered by the Ono Pharmaceutical Company",,10.1016/s0040-4039(00)01016-9,2000-08-01,0.5783050292885489
Tetrahedron,"Synthesis of a novel dioxane nucleoside having two bases, 2(R)-(5-fluorouracil-1-yl)-5(R)-hydroxymethyl-3(R)-(uracil-1-yl)-1,4-dioxane and its 2(S)-isomer, from uridine",,10.1016/s0040-4039(97)01613-4,1997-09-01,0.5782982286303099
Tetrahedron,"Studies towards total synthesis of borrelidin, stereoselective synthesis of the polysubstituted macrolidic part",,10.1016/s0040-4039(97)01371-3,1997-08-01,0.5782952401275109
Organic Letters,Catalytic Enantioselective Total Synthesis of Hypocrolide A,"The first and catalytic enantioselective total synthesis of hypocrolide A (>99% ee) in 12 steps, as well as other botryanes, is described. The absolute configurations of these compounds have been unambiguously confirmed or reassigned accordingly. The key reactions in this study include an unusual rhodium-catalyzed intramolecular [4 + 2] cycloaddition and a biomimetic oxidative [3 + 2] cycloaddition based on our revised biogenetic pathway.",10.1021/acs.orglett.6b02414,2016-09-13,0.5782929923241861
Tetrahedron,An original route to newly-functionalized indoles and carbazoles starting from the ring-opening of nitrothiophenes,,10.1016/j.tetlet.2011.11.137,2011-12-08,0.5782928562880276
Organic Letters,Total Synthesis of the Sesquiterpene (−)-Merrillianin,"The first total synthesis of (−)-merrillianin ( 1 ), which is a natural sesquiterpene with a tricyclic structure having a cyclopentane ring and five- and seven-membered lactone parts, is demonstrated. This asymmetric total synthesis enabled the absolute stereostructure determination of naturally occurring (−)- 1 .",10.1021/acs.orglett.3c03877,2023-12-31,0.5782905359150363
Organic Letters,Synthesis of 4- and 6-Azaindoles via the Fischer Reaction,"Contrary to the common idea that Fischer indole cyclization often cannot be effectively applied to the synthesis of the corresponding azaindoles, we show that this approach can be actually very efficient for the formation of 4- and 6-azaindoles bearing an electron-donating group on the starting pyridylhydrazines. Two 4-azaindole natural product analogues were synthesized in a few steps and very good overall yields.",10.1021/ol902139r,2009-10-19,0.5782823894412953
Tetrahedron,Convergent synthesis of the ABC-ring moiety of zoanthenol: intramolecular Mizoroki–Heck reaction,,10.1016/s0040-4039(01)01110-8,2001-08-01,0.5782781662391523
Synlett,Synthetic Strategies for Understanding Bilirubin Stereochemistry,"All articles of this category Synthetic approaches toward model tetrapyrrolic bilirubin-like analogs are described. The consequences of judiciously targeted remote variations of primary chemical structure on the three-dimensional shape of bilirubin analogs are discussed. 1. Introduction 2. Structural Features of Bilirubin 3. Synthons for Bilirubin Analogs 4. Oxidative Coupling of Dipyrrinones to Give Symmetric Rubins 5. Bilirubin Analogs via Scrambling of Dipyrrinone Subunits, A Route to Unsymmetric Rubins (Mesobilirubin-VIIIα) 6. Synthesis of 10,10-Dimethyl Bilirubin Analogs 7. Synthesis of Carboxyrubin 8. Conclusions",10.1055/s-1994-23004,1994-01-01,0.5782763046007781
Organic Letters,Construction of the Tetracyclic Core Structure of Dysiherbols A–C,"A synthetic study on the construction of the tetracyclic core structure of dysiherbols A–C is presented herein. In this synthesis, intramolecular [2 + 2] cycloaddition introduces a fused 6/4 ring system, followed by a Pd-catalyzed semipinacol rearrangement/C sp2 –H arylation cascade to construct the ring C, and visible-light-mediated ring-opening of cyclopropyl silyl ether installs the tetracyclic core of dysiherbols.",10.1021/acs.orglett.2c00159,2022-02-21,0.578275829647441
Tetrahedron,"Butyl lithium-catalyzed stereoselective telomerization of 1,3-diene - a novel synthesis of N,N-dialkyl(octa-cis-2,6-dienyl)amine derivative -",,10.1016/s0040-4039(01)94221-2,1972-01-01,0.5782710664253904
Organic Letters,"Selective Synthesis of 7-Substituted Purines via 7,8-Dihydropurines","A simple and efficient protocol for the preparation of 7-substituted purines is described. 6- and 2,6-Dihalopurines were N(9)-tritylated and then transformed to 7,8-dihydropurines by DIBAL-H. Subsequent N(7)-alkylation followed by N(9)-trityl deprotection with trifluoroacetic acid was accompanied by spontaneous reoxidation, which led to the 7-substituted purines at 55-88% overall isolated yields.",10.1021/ol1025525,2010-11-19,0.5782693391553517
Synlett,"Enantioselective Synthesis of Dihydrofuranylglycine, Furanylglycine, Furanylalanine and homo-Furanylalanine Derivatives","Enantiomerically pure nor-furanomycin, furanylglycine, furanylalanine and homo-furanylalanine derivatives were prepared from appropriate amino acid derived dienes using ring-closing ­metathesis as the key step.",10.1055/s-2005-871944,2005-01-01,0.5782663150312468
European Journal of Organic Chemistry,Synthesis of15N-Labelled D-Isovaline and α-Aminoisobutyric Acid,"[15N]-D-isovaline was prepared from DL-[α-15N]-α-aminoisovaleramide by enzymatic resolution with Mycobacterium neoaurum. The 15N-isotope was introduced during the Strecker synthesis of its precursor, e.g. aminoisovaleronitrile. Attempts to prepare the amino nitrile precursor of [15N]-α-aminoisobutyric acid (Aib) led to a poor yield and loss of the label. Significantly, improved results were obtained when a cosolvent is present during formation of aminoisobutyronitrile.",10.1002/(sici)1099-0690(200003)2000:5<857::aid-ejoc857>3.0.co;2-v,2000-03-01,0.5782620532775414
Journal of Organic Chemistry,"Stereoselective Synthesis of Indoline, Tetrahydroquinoline, and Tetrahydrobenzazepine Derivatives from <i>o</i>-Bromophenyl <i>N</i>-<i>tert</i>-Butylsulfinyl Aldimines","The diastereoselective addition of an allylic indium intermediate to chiral o-bromophenyl sulfinyl imine 4 proceeded with good levels of diastereoselectivity. The resulting homoallylic amine derivatives were transformed into lactams 7 and 12, which upon copper-mediated intramolecular N-arylation led to the formation of benzo-fused 1-azabicyclo[j.k.0]alkanes 8 and 13. Benzo-fused 2-allyl-substituted heterocycles 14 could also be prepared by means of a palladium-catalyzed N-arylation of the corresponding free amines. The synthesis of the alkaloid (−)-angustureine was easily accomplished from (S)-2-allyltetrahydroquinoline (14b).",10.1021/jo402759v,2014-01-21,0.5782586643402896
Tetrahedron,"An efficient one-pot synthesis of 2-bromo-6-aryl[5H]pyrrolo[2,3-b]pyrazines",,10.1016/j.tetlet.2015.02.005,2015-02-15,0.5782470463175164
Organic Letters,"Efficient Synthesis of a Novel 4-Hydroxy-2,3-dioxocyclobut-1-enyl Group Containing Amino Acids","Syntheses of novel amino acids possessing a squaryl group, 1 − 3, in an optically active form are described. The syntheses of 1 − 3 were conducted by a concise route involving (1) an aldol addition of an enolate derived from Gly, l -Asp, or l -Glu to diisopropyl squarate ( 4 ) and (2) an efficient decarboxylation of the aldol adducts based on the electron-withdrawing property of the squaryl group. Introducing N -protected group to 2 and 3 and peptide formation reactions are also described.",10.1021/ol990286g,1999-10-15,0.5782374099575076
Tetrahedron,Effective and one-step stereo-controlled synthesis of benzyloxylated-diiodopentanes for the synthesis of five-membered imino-sugars,,10.1016/j.tetlet.2013.02.115,2013-03-20,0.5782302170544458
Tetrahedron,The tandem Pummerer-isomünchnone route to (±)-pumiliotoxin C,,10.1016/s0040-4039(97)00141-x,1997-03-01,0.5782197607034574
Synthesis,Stereoselective Total Synthesis of Putaminoxin,"The stereoselective total synthesis of a phytotoxic macrolide putaminoxin, isolated from the culture of Phoma putaminum fungus, has been accomplished by utilization of Sharpless asymmetric epoxidation, Birch reduction, Jacobsen’s kinetic resolution of racemic epoxide, and Yamaguchi lactonization as key transformations.",10.1055/s-0031-1290156,2012-01-16,0.5782170729421707
Journal of Organic Chemistry,"Synthesis of (2<i>R</i>,4<i>S</i>)-4-Amino-5-hydroxybicyclo[3.1.1]heptane-2-carboxylic Acid via an Asymmetric Intramolecular Mannich Reaction","Inhibition of human ornithine aminotransferase interferes with glutamine and proline metabolism in hepatocellular carcinoma, depriving tumors of essential nutrients. A proposed mechanism-based inhibitor containing a bicyclo[3.1.1]heptanol warhead is reported herein. The proposed inactivation mechanism involves a novel α-iminol rearrangement. The synthesis of the proposed inhibitor features an asymmetric intramolecular Mannich reaction, utilizing a chiral sulfinamide. This study presents a novel approach toward the synthesis of functionalized bicyclo[3.1.1]heptanes and highlights an underutilized method to access enantiopure exocyclic amines.",10.1021/acs.joc.4c00781,2024-06-10,0.5782156841170156
Journal of Organic Chemistry,Remarkable β-Selectivity in the Synthesis of β-1-<i>C</i>-Arylglucosides:  Stereoselective Reduction of Acetyl-Protected Methyl 1-<i>C</i>-Arylglucosides without Acetoxy-Group Participation,"An efficient and practical process to generate beta-C-arylglucoside derivatives was achieved. The process described involves Lewis acid mediated ionic reduction of a peracetylated 1-C-aryl methyl glucoside derived from the addition of an aryl-Li to selectively protected delta-D-gluconolactone. The reduction of the 2-acetoxy-1-C-oxacarbenium ion intermediates proceeds with a high degree of selectivity to give beta-C-arylglucosides without 2-acetoxy group participation. Furthermore, during the reduction process we also identified an unprecedented critical role of water. By changing from the usual benzyl ether protecting groups because of cost and chemical compatibility concerns, the new process is made additionally efficient and highly selective.",10.1021/jo071051i,2007-11-13,0.5782144523988209
Tetrahedron,A short synthesis of the Δ-carbopenem ring system,,10.1016/0040-4039(81)80052-4,1981-01-01,0.5782124978071075
Tetrahedron,"A short, enantiospecific synthesis of the 1α-hydroxyvitamin D enyne A-ring synthon",,10.1016/s0040-4039(00)96666-8,1987-01-01,0.5782124978071075
Chemical Science,Benzoquinone-derived sulfinyl imines as versatile intermediates for alkaloid synthesis: Total synthesis of (–)-3-demethoxyerythratidinone,"The preparation and synthetic applications of benzoquinone monoketal-derived N-tert-butanesulfinyl imines is described. These synthetically versatile intermediates undergo highly diastereoselective 1,2-addition reactions with organometallic reagents to provide 4-aminocyclohexadienones in good yields. The utility of this methodology is demonstrated in a six-step enantioselective synthesis of (–)-3-demethoxyerythratidinone.",10.1039/c1sc00095k,2011-01-01,0.5782091645556996
Organic Letters,A Simple Enantioselective Synthesis of Serratenediol,"[reaction: see text] A short synthesis of serratenediol is described, which involves a number of powerful key steps including (1) catalytic enantioselective syntheses of the phenyl sulfone and acylsilane shown above, (2) their coupling, and (3) further stereoselective cationic cyclizations.",10.1021/ol016543a,2001-09-11,0.578206153372298
Journal of Organic Chemistry,5-Aryloxazolidines as Reagents for Double Alkylation of Arenes: A Novel Synthesis of 4-Aryltetrahydroisoquinolines,5-Aryloxazolidines react with arenes under Lewis or Brønsted acid conditions via the Friedel-Crafts/Pictet-Spengler double alkylation sequence to give alkaloid-like 4-aryltetrahydroisoquinolines in 12-94% yields. Three approaches for the controlled insertion of substituents into the target molecules and application of oxazolidine derivatives such as 1-arylethanol-2-amines or 4-hydroxytetrahydroisoquinolines in the alkylation of arenes are also described. An unprecedented two-step easily scalable synthesis of the 4-aryltetrahydroisoquinoline core from aromatic aldehyde was achieved applying oxazolidine methodology.,10.1021/acs.joc.1c01881,2021-09-30,0.5782031298576495
Synthesis,Improved Synthesis of Fluorinated Analogues of Anticancer Active Ether Lipids,"Racemic 2-fluoro-2-(hexadecyloxymethyl)-3-methoxy­propan-1-ol (15a) and its octadecyl homologue 15b were synthesized from ethyl 2-(hexadecyloxymethyl)acrylate (8a) and its homologue 8b, respectively, in five steps (20% or 19% overall yields) using a bromofluorination as the key step. The new compound 15b was transformed into 2′-(trimethylammonium)ethyl-2-methoxymethyl-3-(octadecyloxy)-1-ylphosphate (7b), a fluorinated analogue of anticancer active ether lipids. Enzyme-catalyzed deracemization of the fluorohydrins 15a and 15b using several lipases gave the corresponding enantiomers with low enantiomeric excess in all cases.",10.1055/s-2002-23540,2002-01-01,0.5782014496464251
Journal of the American Chemical Society,"Practical Synthesis of an Open Geodesic Polyarene with a Fullerene-type 6:6-Double Bond at the Center:  Diindeno[1,2,3,4-<i>d</i><i>efg</i>;1‘,2‘,3‘,4‘-<i>m</i><i>nop</i>]chrysene","Diindeno[1,2,3,4-defg;1',2',3',4'-mnop]chrysene (1), the smallest possible alkene-centered C60 substructure with a curved pi-system, is obtained in 25-35% yield by flash vacuum pyrolysis of the twisted 1,1'-dibromobifluorenylidene (2) on a 100 mg scale at 1050 degrees C. At 1200 degrees C, the bowl-shaped hydrocarbon 1 rearranges to the planar isomer diindeno[5,6,7,1-defg;5',6',7',1'-lmnop]chrysene (14) by a double 5/6 ring-expansion/ring-contraction. X-ray crystallography establishes that the central carbon atoms of 1 are nearly 80% as pyramidalized as the carbon atoms of C60 (POAV angles = 9.0 degrees and 11.6 degrees for 1 and C60, respectively). A four-step synthesis has been developed to prepare the pyrolysis precursor (2) as a mixture of (E)- and (Z)-isomers in 39% overall yield from commercially available 9-fluorenone-1-carboxylic acid (10).",10.1021/ja0123148,2002-06-29,0.5781984282442342
Journal of Organic Chemistry,Highly Efficient B(C<sub>6</sub>F<sub>5</sub>)<sub>3</sub>-Catalyzed Hydrosilylation of Olefins,"A convenient and highly efficient method for the Lewis acid-catalyzed trans-selective hydrosilylation of alkenes has been developed. The mechanism of this novel protocol operates via direct addition of silylium type species across C=C bond followed by trapping of the resultant carbenium ion with boron-bound hydride. A number of diversely substituted silanes possessing both aryl and alkyl groups at silicon atom were efficiently prepared using this hydrosilylation methodology. The possibility to employ aryl-containing hydrosilanes in this reaction opens broad capabilities for the synthesis of alcohols via a trans-selective hydrosilylation/Tamao-Fleming oxidation sequence, complementary to the existing cis-selective hydroboration/oxidation protocol.",10.1021/jo016279z,2002-02-26,0.5781954253657214
Journal of the American Chemical Society,Enantioselective Synthesis of Chiral-at-Cage <i>o</i>-Carboranes via Pd-Catalyzed Asymmetric B–H Substitution,"Carborane cage chirality is an outstanding issue of great interest as the icosahedral carboranes have wide applications in medicinal and materials chemistry. The synthesis of optically active carborane derivatives, whose chirality is associated with the substitution patterns on the polyhedron, will open new avenues to carborane chemistry. We report herein an efficient method to achieve chiral-at-cage arylation of o-carboranes with high regio- and enantioselectivities by a strategy of palladium-catalyzed asymmetric intramolecular B-H arylation and cyclization. This represents the first example of the enantioselective reaction on carboranes, providing an efficient way for the construction of chiral-at-cage compounds with new skeletons.",10.1021/jacs.8b01754,2018-03-26,0.5781948862253015
Journal of the American Chemical Society,Total Synthesis of Lehualide B by Allylic Alcohol−Alkyne Reductive Cross-Coupling,"The total synthesis of anticancer marine natural product lehualide B is described. Overall, the synthesis proceeds in just eight steps from a simple gamma-pyrone, does not require the use of protecting groups, and delivers each nonconjugated trisubstituted alkene with high levels of stereoselection. The challenging C12-C16 bis-trisubstituted 1,4-diene was installed with a complex reductive cross-coupling reaction between a preformed Ti-alkyne complex and a pyrone-containing allylic alcohol.",10.1021/ja104782u,2010-08-03,0.5781900986597985
Journal of the American Chemical Society,Total Synthesis of the Norhasubanan Alkaloid Stephadiamine,"(+)-Stephadiamine is an unusual alkaloid isolated from the vine Stephania japonica. It features a norhasubanan skeleton, and contains two adjacent α-tertiary amines, which renders it an attractive synthetic target. Here, we present the first total synthesis of stephadiamine, which hinges on an efficient cascade reaction to implement the aza[4.3.3]propellane core of the alkaloid. The α-aminolactone moiety in a highly hindered position was installed via Tollens reaction and Curtius rearrangement. Useful building blocks for the asymmetric synthesis of morphine and (nor)hasubanan alkaloids are introduced.",10.1021/jacs.8b01918,2018-06-11,0.5781887832840211
Organic Letters,Two Steps to Bicyclo[4.2.0]octadienes from Cyclooctatetraene: Total Synthesis of Kingianic Acid A,"Synthetic approaches to bicyclo[4.2.0]octadiene natural products frequently employ the synthesis of linear tetraenes to initiate a biosynthetic 8π/6π-electrocyclization cascade. This work forges a functionalized bicyclo[4.2.0]octadiene in two steps from cyclooctatetraene. The versatility of this method is demonstrated through natural product synthesis, including the first total synthesis of kingianic acid A and formal syntheses of kingianins A, D, and F and cryptobeilic acid D ethyl ester. The unexpected formation of an E, E, Z, E -tetraene byproduct is rationalized through density functional theory modeling.",10.1021/acs.orglett.2c00325,2022-03-16,0.5781858765086841
Tetrahedron,Synthetic studies toward potent cytotoxic agents amphidinolides G and H: Synthesis of the entire C15C26 moiety of the top half,,10.1016/s0040-4039(98)01699-2,1998-10-01,0.5781855429800914
Tetrahedron,"Synthetic studies toward potent cytotoxic agents amphidinolides: Synthesis of the C1C18 moiety of amphidinolides G, H and L",,10.1016/s0040-4039(98)02009-7,1998-12-01,0.5781855429800914
Journal of Organic Chemistry,"Stereocontrolled Access to Orthogonally Protected <i>anti</i>,<i>anti</i>-4-Aminopiperidine-3,5-diols through Chemoselective Reduction of Enantiopure β-Lactam Cyanohydrins","The cyanosilylation of enantiopure 4-oxoazetidine-2-carbaldehydes with tert-butyldimethylsilyl cyanide was promoted by either molecular sieves or catalytic amount of sodium carbonate to give O-silylated beta-lactam cyanohydrins with good yield and diastereoselectivity. In contrast, Lewis acids did not effectively promote the cyanosilylation under different experimental conditions, and instead hydrocyanation took place affording the corresponding free cyanohydrins in variable yield and selectivity. Starting from beta-lactam cyanohydrin hybrids, two concise, complementary stereocontrolled routes to optically pure orthogonally protected anti,anti-4-amino-3,5-piperidine diols were achieved. Key features of the first approach include chemoselective reductive opening of the beta-lactam ring with LiBH4 to a 3-amino-5-hydroxy pentanenitrile followed by reductive cyclization of a conveniently functionalized cyanomesylate derivative with NaBH4/NiCl2. The second approach involves LiAlH4 reduction of protected anti,anti-4-amino-3,5-dihydroxypiperidin-2-ones, which were easily obtained by chemoselective reduction of the cyano group in the beta-lactam cyanohydrin hybrids with NaBH4/NiCl2 and subsequent intramolecular rearrangement of the resulting amino beta-lactams. Both routes make use of an oxidative N-dearylation with diacetoxyiodobenzene of a 4-methoxyphenylamino group as a common synthetic step. Specifically, the utility of this novel reaction sequence has been demonstrated by the synthesis of fully orthogonally protected sialidase inhibitors.",10.1021/jo701452a,2007-09-15,0.5781853264311876
Tetrahedron,"A practical, two-step synthesis of 1-alkyl-4-aminopyrazoles",,10.1016/j.tetlet.2008.02.169,2008-03-05,0.5781837676796284
Synlett,A New Approach to Asymmetric Synthesis of <i>β</i>-Amino Alcohols by Means of <i>α</i>-Chirally Protected Amino Alkyllithiums,"All articles of this category A new, general synthetic approach to enantiopure α -amino ketones and syn - β -amino alcohols is described which employs the doubly chiral N-protected α -amino alkyllithiums generated via Pearson's transmetalative protocol as the key synthetic intermediates. chiral α -amino alkyllithium - asymmetric synthesis - β -amino alcohol - α -amino ketone",10.1055/s-1998-1891,1998-10-01,0.5781802611966228
Organic Letters,Total Synthesis of<i>ent</i>-Pregnanolone Sulfate and Its Biological Investigation at the NMDA Receptor,"A unique asymmetric total synthesis of the unnatural enantiomer of pregnanolone, as well as a study of its biological activity at the NMDA receptor, is reported. The asymmetry is introduced by a highly atom-economic organocatalytic Robinson annulation. A new method for the construction of the cyclopentane D-ring consisting of Cu I -catalyzed conjugate addition and oxygenation followed by thermal cyclization employing the persistent radical effect was developed. ent- Pregnanolone sulfate is surprisingly only 2.6-fold less active than the natural neurosteroid.",10.1021/acs.orglett.7b03838,2018-01-24,0.5781720289616901
Organic Process Research & Development,Catalytic Enantioselective Synthesis of Key Propargylic Alcohol Intermediates of the Anti-HIV Drug Efavirenz,"The catalytic, enantioselective synthesis of key propargylic alcohol intermediates toward the synthesis of the anti-HIV drug efavirenz is reported. Using a recently reported chiral-at-ruthenium catalyst ( J. Am. Chem. Soc. 2017, 139, 4322), catalytic enantioselective alkynylations of 1-(2,5-dichlorophenyl)-2,2,2-trifluoroethanone (99% yield, 95% ee) and 1-(5-chloro-2-nitrophenyl)-2,2,2-trifluoroethanone (97% yield, 99% ee) are achieved using catalyst loadings of merely 0.2 mol % (ca. 500 TON).",10.1021/acs.oprd.7b00376,2018-01-09,0.5781685424128491
Organic Process Research & Development,"Investigation of the Stereoselective Synthesis of the Indane Dimer PH46A, a New Potential Anti-inflammatory Agent","High Resolution Image Download MS PowerPoint Slide PH46A, belonging to a class of 1,2-Indane dimers, has been developed by our research group as a potential therapeutic agent for the treatment of inflammatory and autoimmune diseases. The initial synthetic route to PH46A gave a low overall yield, due in large part to the generation of undesired diastereoisomer 5 and the unwanted enantiomer ( R, R )- 8 during the synthesis. The aim of this work was to carry out a comprehensive investigation into the stereoselective synthesis of PH46A. Significant progress was made on the ketone reduction step, where the use of triisobutylaluminum [TiBA, Al(iBu) 3 ] afforded high selectivity for the target diastereoisomer ( rac )- 6, compared to the unfavorable ratio obtained using a previous process. This enabled a multikilo scale synthesis of PH46A in a GMP environment. Further, a brief proof-of-principle investigation was carried out using an achiral phase transfer catalyst (PTC) for alkylation at the methine carbon of the parent indanone.",10.1021/acs.oprd.7b00258,2017-11-27,0.5781678277043608
Synthesis,Total Synthesis of 6-O-Benzoylzeylenol from Diacetone Glucose,"A total synthesis of 6- O -benzoylzeylenol from diacetone glucose is described. The key steps were a crossed aldol–Cannizzaro reaction to create a quaternary carbon stereocenter, and cyclization through ring closure metathesis (RCM). Of the four stereogenic centers, two were derived from diacetone glucose, the quaternary stereocenter was created by means of the crossed aldol–Cannizzaro reaction, and the fourth stereogenic center was produced by a Sharpless asymmetric epoxidation. Finally, cyclization through RCM and deprotection by removal of a benzyl group with titanium(IV) chloride gave the target molecule.",10.1055/s-0033-1340903,2014-03-27,0.5781673784905561
Tetrahedron,A novel convenient one step pyrimidine synthesis,,10.1016/s0040-4039(01)90348-x,1981-01-01,0.5781669773732685
Tetrahedron,"A highly efficient synthesis of natural PGE3 and 5,6-dihydro PGE3 via two-component coupling process",,10.1016/s0040-4039(00)99365-1,1989-01-01,0.5781665937463878
Tetrahedron,"Bis and tetrakis(6-methyl-1,4-dithiafulven-6-yl) substituted tetrathiafulvalenes (TTF) and their vinylogs as novel π-donors",,10.1016/s0040-4039(97)00035-x,1997-02-01,0.5781616351100832
Tetrahedron,A new allenic dianion: selective mono and bialkylation.,,10.1016/s0040-4039(01)96504-9,1971-01-01,0.5781602433147158
Angewandte Chemie International Edition,High-Yielding Enantioselective Synthesis of the Macrolactam Aglycon of Sch 38516 from Two Units of (2R)-2-Ethyl-4-penten-1-ol,"The same precursor—namely, (2R)-2-ethyl-4-penten-1-ol—was used to obtain fragments C9–C13 and C1–C8 of 1, the aglycon of Sch 38516 (which is active against Candida sp.) and fluvirucin B1 (which is active against influenza A virus). The key steps of the synthesis were the aldol-like reaction between the two fragments and the macrolactamization of a 13-azidotridecanoic acid derivative (see scheme). MOM=methoxymethyl, Py=2-pyridyl.",10.1002/(sici)1521-3773(19991018)38:20<3086::aid-anie3086>3.3.co;2-4,1999-10-18,0.5781583318706521
Angewandte Chemie International Edition,High-Yielding Enantioselective Synthesis of the Macrolactam Aglycon of Sch 38516 from Two Units of (2R)-2-Ethyl-4-penten-1-ol,"The same precursor-namely, (2R)-2-ethyl-4-penten-1-ol-was used to obtain fragments C9-C13 and C1-C8 of 1, the aglycon of Sch 38516 (which is active against Candida sp.) and fluvirucin B(1) (which is active against influenza A virus). The key steps of the synthesis were the aldol-like reaction between the two fragments and the macrolactamization of a 13-azidotridecanoic acid derivative (see scheme). MOM=methoxymethyl, Py=2-pyridyl.",10.1002/(sici)1521-3773(19991018)38:20<3086::aid-anie3086>3.0.co;2-d,1999-10-18,0.5781583318706521
Tetrahedron,A short formal synthesis of paroxetine. Diastereoselective cuprate addition to a chiral racemic olefinic amido ester,,10.1016/s0040-4039(01)01666-5,2001-10-01,0.5781575930532225
Journal of Organic Chemistry,Biomimetic Synthesis of Isorosmanol and Przewalskin A,"terpenoid with anti-HIV-1 activity from Salvia przewalskii Maxim, was formed in 10 steps via isorosmanol from (+)-carnosic acid. The synthetic strategy was inspired primarily by the biogenetic hypothesis and was enabled by epoxidation, epoxide ring opening, and lactonization in one pot to prepare the 11,12-dimethoxy isorosmanol, and bismuthonium ylide-induced ring expansion of o-quinone to construct the 2-acyl-3-hydroxytropone.",10.1021/acs.joc.7b02369,2017-12-01,0.5781530849247198
Journal of Organic Chemistry,"Synthesis and Absolute Configuration of Novel <i>N</i>,<i>O</i>-Psiconucleosides Using (<i>R</i>)-<i>N</i>-Phenylpantolactam as a Resolution Agent","A series of novel N,O-psiconucleosides has been prepared in both enantiomeric forms by resolution of an advanced racemic synthetic intermediate using (R)-N-phenylpantolactam as a chiral resolution agent. The absolute configuration of all of these compounds has been unequivocally established by chemical correlation with the novel (R)- or (S)-1-methyl-5-phenylpyrrolidine-2,3-dione, prepared from the known (R)- and (S)-1-methyl-5-phenylpyrrolidin-2-one, respectively.",10.1021/jo800769m,2008-07-29,0.5781523094661782
Organic Letters,An Approach to the Total Synthesis of Welwistatin,An approach to the total synthesis of the antimicrotubule agent welwistatin is described. Key transformations include (1) a 7-endo intramolecular conjugate addition reaction of enone 6 to deliver the strained bicyclo[4.3.1]decanone 5; (2) a 6pi electrocyclic ring closure of trienecarbamate 16 followed by oxidation to afford protected aniline 17; and (3) an intramolecular cyclization of acetic acid derivative 18 to give rise to indole 19. [reaction: see text],10.1021/ol0608799,2006-05-17,0.5781522247927308
Synthesis,An Efficient Synthesis of Novel Dibenzo-Fused Nine-Membered Oxacycles Using a Sequential Baylis-Hillman Reaction and Radical Cyclization,"A short and high yield synthetic route to novel dibenz[b,g]oxonins, one of which has been characterized by X-ray crystallography, has been developed based on a sequential Baylis-Hillman reaction and radical cyclization. The regioselective radical cyclization followed a 9-endo-trig pathway. © Georg Thieme Verlag Stuttgart.",10.1055/s-2007-1000827,2007-12-20,0.5781519639820191
Journal of Organic Chemistry,Total Synthesis of (+)-Geldanamycin and (−)-<i>o</i>-Quinogeldanamycin:  Asymmetric Glycolate Aldol Reactions and Biological Evaluation,"The total synthesis of (+)-geldanamycin (GA), following a linear route, has been completed using a demethylative quinone-forming reaction as the last step. Key steps include the use of two new asymmetric boron glycolate aldol reactions. To set the anti-C11,12 hydroxymethoxy functionality, (S,S)-5,6-bis-4-methoxyphenyldioxanone 8 was used. Methylglycolate derived from norephedrine 5 set the C6,7 methoxyurethane stereochemistry. The quinone formation step using nitric acid gave the non-natural o-quino-GA product 55 10:1 over geldanamycin. Other known oxidants gave an unusual azaquinone product 49. o-Quino-GA 55 binds Hsp90 with good affinity but is less cytotoxic compared to GA.",10.1021/jo034870l,2003-09-26,0.5781495705924965
Journal of the American Chemical Society,Total Synthesis of (−)-Himgaline,"The first total synthesis of (-)-himgaline and a highly enantioselective synthesis of its congener (-)-GB 13 are described. Decarboxylative aza-Michael reaction of the hexacyclic lactone precursor under acidic conditions, followed by basic workup, yielded (-)-GB 13 in 80% yield. Cyclization of (-)-GB 13 to oxohimgaline under acidic conditions, followed by internally coordinated sodium triacetoxyborohydride reduction, gave (-)-himgaline as the exclusive product.",10.1021/ja065198n,2006-09-08,0.5781426273275554
Organic Letters,Formal Synthesis of (−)-Haliclonin A: Stereoselective Construction of an Azabicyclo[3.3.1]nonane Ring System by a Tandem Radical Reaction,"A formal synthesis of (−)-haliclonin A, isolated from the marine sponge Haliclona sp. in Korea, is described. The key feature of the synthesis includes the highly stereoselective tandem radical reaction to construct the azabicyclo[3.3.1]nonane core and the enantioselective formation of an all-carbon quaternary center via the Pd-mediated deracemization.",10.1021/acs.orglett.0c01627,2020-06-17,0.5781351467398151
Journal of the American Chemical Society,Synthesis and Absolute Stereochemical Assignment of (+)-Miyakolide,"The first total synthesis of the marine macrolide miyakolide has been achieved, and its absolute stereochemistry has been determined. The carbon skeleton is assembled in a convergent fashion from three fragments via esterification, [3 + 2] dipolar cycloaddition, and aldol addition. The utility of β-ketoimide aldol reactions in fragment coupling was demonstrated on fully elaborated intermediates. The coupled material was transformed into a 1,3,7-triketone-containing macrocycle that underwent a facile transannular aldol reaction followed by hemiketalization to form the oxydecalin ring system of the natural product. Deprotection afforded ent -miyakolide, which was produced in 6.8% overall yield and 29 linear steps.",10.1021/ja990789h,1999-07-01,0.578134151377271
Organic Letters,Total Synthesis of Stachybotrys microspora Triprenol Phenol-7 (SMTP-7),"The first total synthesis of Stachybotrys microspora triprenol phenol (SMTP)-7 is described. Establishment of the two pyran ring stereogenic centers and key reactions featuring a double reductive amination and a double lactam ring formation in flow are described. The (2 R,3 S )- trans -benzopyran intermediate 7A, isolated by chiral preparative SFC chromatography, was carried forward to afford SMTP-7. Analytical data for synthetic SMTP-7, including 1 H and 13 C NMR data, HPLC retention time, and UV spectrum, were in excellent agreement with those for natural SMTP-7.",10.1021/acs.orglett.3c04106,2024-01-17,0.57813149113884
European Journal of Organic Chemistry,Divergent and Concise Syntheses of Spiroisoxazolines: First Total Synthesis of 11‐Deoxyfistularin‐3,Abstract A divergent and concise base‐promoted Dieckmann‐type keto‐ester condensation strategy is demonstrated to generate two unique spiro[cyclohexadiene‐isoxazoline] moieties. The consecutive di‐bromination–elimination–bromination of the corresponding spiro moiety has been successfully utilized to furnish the desired core structure of many bromotyrosine derived spiroisoxazoline natural products. The spiroisoxazoline acid was further coupled with the desired diamine to accomplish the first total synthesis of 11‐deoxyfistularin‐3. This strategy could serve as an efficient alternative to previously developed oxidative dearomatizing spirocyclization of phenol as the essential step to synthesize this class of natural products.,10.1002/ejoc.201500603,2015-07-14,0.5781289332512327
Journal of Organic Chemistry,Formal Total Synthesis of Neocarzinostatin Chromophore,"[reaction: see text] An efficient route to the neocarzinostatin chromophore aglycon has been developed. The present strategy involves a stereoselective intramolecular acetylide-aldehyde cyclization to form the C5-C6 bond, followed by efficient installation of alpha-epoxide, naphthoate, and carbonate functionalities. The C8-C9-olefin was introduced by using the Martin sulfurane dehydration reaction to furnish the highly reactive aglycon.",10.1021/jo052031o,2005-12-20,0.5781275952657557
Synlett,"First Synthesis of Xerulin, an Inhibitor of the Biosynthesis of Cholesterol",All articles of this category butenolides - butyrolactones - C-C coupling - β-elimination - Wittig reaction,10.1055/s-1999-3162,1999-08-01,0.5781227920183715
Tetrahedron,"Oscillamide Y, a chymotrypsin inhibitor from toxic Oscillatoria agardhii",,10.1016/0040-4039(95)01198-q,1995-08-01,0.5781124865863606
Tetrahedron,"Oscillatorin, a chymotrypsin inhibitor from toxic Oscillatoria agardhii",,10.1016/0040-4039(96)01501-8,1996-09-01,0.5781124865863606
Tetrahedron,"Oscillamide Y, A Chymotrypsin Inhibitor from Toxic Oscillatoria Agardhii",,10.1016/00404-0399(50)1198q-,1995-08-14,0.5781124865863606
Synthesis,An Asymmetric Synthesis of Clopidogrel Hydrogen Sulfate,"An asymmetric synthesis of ( S )-(+)-clopidogrel hydrogen sulfate has been developed through application of a Strecker reaction with [(1 S )-1-(4-methoxyphenyl)ethyl]amine hydrochloride as a chiral auxiliary. Addition of 2-chlorobenzaldehyde to a solution of sodium cyanide and [(1 S )-1-(4-methoxyphenyl)ethyl]amine hydrochloride­ gave diastereoisomerically pure (2 S )-(2-chlorophenyl){[(1 S )-1-(4-methoxyphenyl)ethyl]amino}acetonitrile hydro­chlor­ide. Cleavage of the chiral auxiliary and concomitant hydrolysis of the nitrile group then gave enantiomerically pure (2 S )-2-(2-chlorophenyl)glycine hydrochloride, a key intermediate for ( S )-(+)-clopidogrel.",10.1055/s-0032-1316852,2013-02-05,0.5781103467435238
Tetrahedron,"Chiral formamidines. Asymmetric synthesis of 1,1-disubstituted tetrahydroisoquinolines.",,10.1016/0040-4039(91)80068-h,1991-09-01,0.5781096513391059
Synlett,A Chiral Base Desymmetrisation-Ring-Closing Metathesis Route to Chiral Azaspirocycles: Synthesis of Core Structures Related to Pinnaic Acid and Halichlorine,"A range of highly functionalised chiral azaspirocycles was synthesised, starting from a piperidine diester that is available in 90% ee from a chiral base desymmetrisation. The approach depends upon the use of Grignard addition reactions or a Claisen rearrangement to provide intermediates capable of undergoing ring-closing metathesis. A number of intermediates related to the core structure of pinnaic acid were synthesised by concise routes using the approach.",10.1055/s-2004-831335,2004-01-01,0.5781078508053712
Journal of Organic Chemistry,Enantiomerically Pure Tetrahydropyrimidinones in Asymmetric Synthesis:  Preparation of a Protected α-Methylasparagine Derivative and Corresponding Dipeptides,"Methyl ester 5a, available in enantiomerically pure form from the amino acid asparagine via a one-pot cyclization/protection sequence, followed by esterification, can be effectively deprotonated with LDA/DMPU/LiCl. Treatment with MeI affords the corresponding alkylated adduct in enantiomerically pure form, from which α-methylaspartic acid is obtained. Variation of the amine protection group allows for the isolation of a protected carboxylic acid/free amine derivative of α-methylasparagine. The utility of H-MeAsn-OMe is demonstrated in the formation of dipeptides.",10.1021/jo9909296,1999-09-23,0.5781077618688507
Organic Letters,Synthesis of Novel Spiro[2.3]hexane Carbocyclic Nucleosides via Enzymatic Resolution,"[reaction: see text] Novel R- and S-spiro[2.3]hexane nucleosides have been synthesized. The key step involved the Pseudomonas cepacia lipase catalyzed resolution of racemic compound 2, synthesized in seven steps starting from diethoxyketene and diethyl fumarate, to give (+)-acetate 3 and (-)-alcohol 13. (+)-Acetate 3 and (-)-acetate 14 were converted to R- and S-9-(6-hydroxymethylspiro[2.3]hexane)-4-adenine, respectively.",10.1021/ol0491989,2004-06-30,0.5781068117518867
Tetrahedron,Improved synthesis of natural isomeric naphthoxanthenones,,10.1016/j.tetlet.2019.151359,2019-11-04,0.5780994039540663
Tetrahedron,"A practical and efficient synthesis of complex-type biantennary heptasaccharide-asparagine conjugate, a key building block for the synthesis of complex N-linked glycopeptides",,10.1016/s0040-4039(97)01036-8,1997-07-01,0.5780982373603624
Synlett,New Synthetic Approach to Aminosquarylium Cyanine Dyes,"A novel synthesis of aminosquarylium cyanine dyes, based on the methylation of readily available squarylium dyes with methyl triflate, followed by nucleophilic substitution with appropriate aliphatic amines, was disclosed. By this procedure several new aminosquarylium cyanine dyes bearing benzothiazole, benzoselen­azole and quinoline nuclei were prepared.",10.1055/s-2002-34226,2002-01-01,0.5780979779945793
Synlett,Asymmetric Synthesis of Di- and Trisubstituted Cyclopropanes through an Intramolecular Ring Closure,"An asymmetric synthesis of di- and trisubstituted cyclopropanes proceeding through an intramolecular ring closure of activated chiral benzyl alcohols has been developed. The chiral alcohol intermediates are obtained from asymmetric reduction of readily available 1,4-keto esters and undergo a one-pot activation and ring closure to provide the ester-functionalized cyclopropanes in high enantio- and diastereomeric purity. This methodology avoids the use of hazardous diazo and alkyl zinc reagents commonly employed in cyclopropanation reactions.",10.1055/s-0030-1259535,2011-02-08,0.5780935924968282
Angewandte Chemie International Edition,Stereodivergent Attached‐Ring Synthesis via Non‐Covalent Interactions: A Short Formal Synthesis of Merrilactone A,A strategy to control the diastereoselectivity of bond formation at a prochiral attached-ring bridgehead is reported. An unusual stereodivergent Michael reaction relies on basic vs. Lewis acidic conditions and non-covalent interactions to control re- vs. si- facial selectivity en route to fully substituted attached-rings. This divergency reflects differential engagement of one rotational isomer of the attached-ring system. The successful synthesis of an erythro subtarget diastereomer ultimately leads to a short formal synthesis of merrilactone A.,10.1002/anie.202114514,2021-11-25,0.5780900550967675
Organic Letters,"Unprecedented One-Pot, Domino Tertiary Alcohol Protection–Michael Type Addition of Halides to Morita–Baylis–Hillman Adduct of Isatin with RCOX/K<sub>2</sub>CO<sub>3</sub>: Diastereoselective Synthesis of Oxindole Appended β-Halo Esters","A facile method utilizing RCOX/K2CO3 as a novel reagent for conjugate addition of hydrogen halide, in addition to tertiary (3°)-hydroxyl protection that leads to the synthesis of functionalized β-halo Morita-Baylis-Hillman ester appended oxindoles, has been developed. The diastereoselective one-pot O-acylation-hydrohalogenation observed cannot otherwise be performed by treatment with hydrohalide. Deprotection of a 3°-hydroxyl protecting group has also been demonstrated by treatment with hydrochloric acid.",10.1021/ol303554c,2013-03-05,0.5780864864759077
Synthesis,Palladium-Catalyzed Routes to Geranylated or Farnesylated Phenolic Stilbenes: Synthesis of Pawhuskin C and Schweinfurthin J,"Starting from double MOM-protected phloroglucinol, the facile total syntheses of bioactive natural products pawhuskin C and schweinfurthin J were accomplished in good overall yields. The Heck, Stille, or Suzuki coupling reactions of two different electron-rich phenolic segments bearing geranylated or farnesylated units were involved in the decisive step. The Sonogashira coupling reaction followed by palladium-catalyzed chemo- and stereoselective cis -reduction of an alkyne unit and subsequent isomerization to give the desired natural products is also described.",10.1055/s-0032-1316765,2012-08-08,0.5780841059864387
European Journal of Organic Chemistry,"A New Synthesis of (−)-Frontalin, the Bark Beetle Pheromone","(−)-Frontalin [(1S,5R)-1,5-dimethyl-6,8-dioxabicyclo[3.2.1]- octane (1)] was synthesized from ethyl 2-oxocyclopentane-1-carboxylate (2) as the starting material. Baker′s yeast was used for the asymmetric reduction of 2 to 3. The S configuration at C-1 of 1 was generated by diastereoselective methylation of the dianion derived from 3 to give 4. The present process furnished about 10 g of 1 with enantiomeric purity of 89.1% e.e.",10.1002/(sici)1099-0690(199802)1998:2<233::aid-ejoc233>3.0.co;2-m,1998-02-01,0.5780825271110858
Tetrahedron,Total synthesis of (±)-γ-lycorane via the electrocyclic ring closure of a divinylpyrroline,,10.1016/j.tetlet.2011.09.138,2011-10-17,0.5780790084575497
European Journal of Organic Chemistry,From Chondroitin Polymer to Size‐Defined Hyaluronan Oligosaccharides,"Abstract Efficient and stereocontrolled synthesis of size‐defined hyaluronan oligomers is described for the first time starting from natural chondroitin polymer. Semisynthesis from chondroitin polymer afforded a disaccharide fragment that was used as starting material for the efficient preparation of a protected hyaluronic acid disaccharide building block. Selective inversion of configuration at C‐4 of the D ‐galactosamine in the chondroitin disaccharide was one of the key steps necessary to afford a hyaluronic disaccharide skeleton. Stereoselective glycosylation, efficient reduction of the N ‐trichloroacteyl group into the corresponding N ‐acetyl group and deprotection afforded hyaluronan oligomers in good yield.",10.1002/ejoc.201300893,2013-09-09,0.578079008306054
Organic Letters,"Enantiospecific, Stereospecific Total Synthesis of (+)-Majvinine, (+)-10-Methoxyaffinisine, and (+)-<i>N</i><sub>a</sub>-Methylsarpagine as Well as the Total Synthesis of the <i>Alstonia</i> Bisindole Macralstonidine","[structure: see text] The enantiospecific stereospecific total synthesis of majvinine 1a, 10-methoxyaffinisine 1b, and N(a)-methylsarpagine 1c are reported; this method has also resulted in the total synthesis of the Alstonia bisindole macralstonidine 2.",10.1021/ol010222h,2002-02-08,0.5780777932441716
Synlett,Syntheses of Fawcettimine-Type Lycopodium Alkaloids Utilizing the Pauson-Khand Reaction,"The asymmetric total syntheses of some fawcettimine-type Lycopodium alkaloids, utilizing an intramolecular Pauson–Khand reaction as the key step, are described. 1 Introduction 2 First Asymmetric Total Syntheses of Lycoposerramine-C and Phlegmariurine A 3 First Asymmetric Total Synthesis of Huperzine Q 4 Total Syntheses of Fawcettimine and Fawcettidine 5 Conclusion",10.1055/s-0032-1316680,2012-08-08,0.5780746515309426
Organic Letters,Synthesis of a Val-Pro Diaminodiol Dipeptide Isostere by Epoxyamine Cyclization,"[reaction: see text] The stereoselective synthesis of a novel proline-containing dipeptide isostere is described. Starting from l-valine, three new contiguous stereocenters are generated by asymmetric induction and epoxide chemistry, while the pyrrolidine ring of proline is introduced in the final step via intramolecular ring opening of the amino acid derived epoxyamine. Proline-containing peptidomimetics are potentially attractive as selective inhibitors of proline-specific enzymes, such as PPIases and retroviral proteases, and as analogues of bioactive peptides.",10.1021/ol0499147,2004-02-24,0.5780741663656369
Organic Letters,Total Syntheses of Phleghenrines A and C,"High Resolution Image Download MS PowerPoint Slide Herein, we report the total syntheses of phleghenrines A and C from commercially available starting materials in 7 and 8 steps, respectively. Notable steps include an inverse electron-demand Diels–Alder reaction between a masked o -benzoquinone and a N -protected enamine to prepare one key intermediate with a bicyclo[2.2.2]octenone core, a Büchner–Curtius–Schlotterbeck one-carbon insertion to expand the bicyclo[2.2.2]octenone to a bicyclo[3.2.2]nonenone, and Trauner’s modified 2-pyridone synthesis to install the 2-pyridone moiety.",10.1021/acs.orglett.3c01784,2023-07-11,0.5780718451735384
Tetrahedron,Conceptually new chiral tertiary C2 symmetric diamines in asymmetric synthesis,,10.1016/j.tetlet.2003.09.171,2003-11-07,0.5780685379161872
Synthesis,"Stereoselective Synthesis of 1′,2′-cis-Disubstituted Carbocyclic ribo-Nucleoside Analogues","Herein we disclose an efficient strategy for the convergent synthesis of 1′,2′-cis-disubstituted carbocyclic ribo-nucleoside analogues. Starting from an enantiomerically pure cyclopentenol precursor, the key step for the preparation of the highly functionalized carbocyclic building block is an asymmetric dihydroxylation. Employing different variants of the Mitsunobu protocol, the condensation with all-natural nucleobases or their precursors affords a series of ribo-configured carbocyclic 1′,2′-cis-disubstituted nucleoside analogues.",10.1055/s-0036-1591732,2017-12-20,0.5780667383185414
Angewandte Chemie International Edition,"Total Synthesis of (±)‐<i>trans</i>‐Dihydronarciclasine through a Highly <i>endo</i>‐Selective Diels–Alder Cycloaddition of 3,5‐Dibromo‐2‐pyrone","All essential functional groups in the natural product (±)-trans-dihydronarciclasine (1) were introduced with the correct relative configuration in a highly endo-selective Diels–Alder cycloaddition of 3,5-dibromo-2-pyrone with a styrene dienophile (see scheme). The total synthesis of 1 from these starting materials was completed in 11 steps and 15.8 % overall yield.",10.1002/anie.200604612,2007-02-15,0.5780660854459494
Tetrahedron,Synthesis of 1-oxacephams via improved cyclization of N-substituted-4-formyloxyazetidin-2-ones,,10.1016/s0040-4039(98)01841-3,1998-11-01,0.5780627216252613
Synlett,"Synthesis of cis-4,5-Diarylazepanes","Substituted cis-4,5-diarylazepanes are synthesized in modest overall yields starting from 5,5-diarylazepan-4-ones by a ­reduction, mesylation, rearrangement, and hydrogenation reaction sequence.",10.1055/s-0030-1260974,2011-07-25,0.5780612812443314
Journal of Organic Chemistry,Synthesis of Galactofuranose-Containing Acceptor Substrates for Mycobacterial Galactofuranosyltransferases,"The major structural component of the cell wall in Mycobacterium tuberculosis, infection by which causes tuberculosis, is the mycolyl-arabinogalactan (mAG) complex. This large glycoconjugates has at its core a backbone of approximately 30 D-galactofuranose (Gal(f)) residues that are linked to peptidoglycan by way of a linker disaccharide containing L-rhamnose and 2-acetamido-2-deoxy-D-glucose. Recent studies have supported a model of galactan biosynthesis in which the entire structure is assembled by the action of two bifunctional galactofuranosyltransferases. These biochemical investigations were made possible, in part, by access to a panel of oligosaccharide fragments of the mAG complex (1-12), the synthesis of which we describe here. An early key finding in this study was that the iodine-promoted cyclization of galactose diethyl dithioacetal (19) in the presence of an alcohol solvent led to the formation Gal(f) glycosides contaminated with no pyranoside isomer, thus allowing the efficient preparation of furanoside derivatives of this monosaccharide. The synthesis of disaccharide targets 1, 2, 11 and 12 proceeded without difficulty through the use of thioglycoside donors and octyl glycoside acceptors, both carrying benzoyl protection. In the synthesis of the tri- and tetrasaccharides 3-6, we explored routes in which the molecule was assembled from the reducing to nonreducing end, and the reverse. The latter approach was found to be preferable for the preparation of 6, and in the case of 3 and 4, this strategy allowed the development of efficient one-pot methods for their synthesis. We have also carried out the first synthesis of three mAG fragments (8-10) consisting of the linker disaccharide further elaborated with one, two or three Gal(f) residues. A key step in the synthesis of these target compounds was the coupling of a protected linker disaccharide derivative (58) with a mono-, di-, or trigalactofuranosyl thioglycoside (17, 54, or 53, respectively).",10.1021/jo800457j,2008-05-20,0.5780567343697046
Tetrahedron,The total synthesis of chilenine: Novel constructions of cyclic enamides,,10.1016/s0040-4039(00)99115-9,1989-01-01,0.5780503384480146
Angewandte Chemie International Edition,Total Synthesis of (+)-Saponaceolide B,"Coupling of three fragments results in the first total synthesis of a saponaceolide (see scheme). The first fragment, the spiroketal portion, is formed from two moieties, one derived from geraniol and the other from allyl malonate. A sulfone alkylation-desulfonylation sequence joins the spiroketal portion to the methylene-3,3-dimethylcyclohexane unit. The subsequent stereoselective Wittig reaction attaches the final piece to complete the synthesis of saponaceolide B (1), one of the most biologically active members of this family.",10.1002/(sici)1521-3773(19991216)38:24<3664::aid-anie3664>3.0.co;2-q,1999-12-16,0.5780466541959536
Angewandte Chemie International Edition,Total Synthesis of (+)-Saponaceolide B,"Coupling of three fragments results in the first total synthesis of a saponaceolide (see scheme). The first fragment, the spiroketal portion, is formed from two moieties, one derived from geraniol and the other from allyl malonate. A sulfone alkylation–desulfonylation sequence joins the spiroketal portion to the methylene-3,3-dimethylcyclohexane unit. The subsequent stereoselective Wittig reaction attaches the final piece to complete the synthesis of saponaceolide B (1), one of the most biologically active members of this family.",10.1002/(sici)1521-3773(19991216)38:24<3664::aid-anie3664>3.3.co;2-h,1999-12-16,0.5780466541959536
Tetrahedron,Studies toward the total synthesis of gambieric acids: convergent synthesis of the GHIJ-ring fragment having a side chain,,10.1016/j.tetlet.2010.11.127,2010-11-30,0.5780421553160509
Journal of the American Chemical Society,"Lobatamide C:  Total Synthesis, Stereochemical Assignment, Preparation of Simplified Analogues, and V-ATPase Inhibition Studies","The total synthesis and stereochemical assignment of the potent antitumor macrolide lobatamide C, as well as synthesis of simplified lobatamide analogues, is reported. Cu(I)-mediated enamide formation methodology has been developed to prepare the highly unsaturated enamide side chain of the natural product and analogues. A key fragment coupling employs base-mediated esterification of a beta-hydroxy acid and a salicylate cyanomethyl ester. Three additional stereoisomers of lobatamide C have been prepared using related synthetic routes. The stereochemistry at C8, C11, and C15 of lobatamide C was assigned by comparison of stereoisomers and X-ray analysis of a crystalline derivative. Synthetic lobatamide C, stereoisomers, and simplified analogues have been evaluated for inhibition of bovine chromaffin granule membrane V-ATPase. The salicylate phenol, enamide NH, and ortho-substitution of the salicylate ester have been shown to be important for V-ATPase inhibitory activity.",10.1021/ja0352350,2003-06-06,0.5780420348862035
Journal of Organic Chemistry,A Route to Triazole-Fused Sultams via Metal-Free Base-Mediated Cyclization of Sulfonamide-Tethered 5-Iodotriazoles,"An efficient direct approach to triazole-fused sultams has been developed. The key step of the proposed strategy is base-mediated cyclization of sulfonamide-tethered 5-iodo-1,2,3-triazoles which are readily available via an improved protocol for Cu-catalyzed 1,3-dipolar cycloaddition. The annulation of the sultam fragment to the triazole ring proceeds smoothly under transition-metal-free conditions in the presence of Cs 2 CO 3 in dioxane at 100 °C and affords fused heterocycles in high yields up to 99%. The favorability of an S N Ar-like mechanism for the cyclization was supported by DFT calculations. The applicability of the developed procedure to modification of natural compounds was demonstrated by preparation of a deoxycholic acid derivative.",10.1021/acs.joc.0c00520,2020-05-21,0.5780405134536564
Journal of Organic Chemistry,From Chiral <i>ortho</i>-Benzoquinone Monoketals to Nonracemic Indolinocodeines through Diels–Alder and Cope Reactions,"The S-dienol (-)-4 containing 10 carbons and one oxygen of the final product was prepared in 98.6% ee and 39% yield from cyclohexan-1,3-dione. It was attached to the aromatic ring as a monoether of catechol S-(-)-6 and subsequently subjected to oxidative ketalization in methanol. The allylated phenanthrofuran obtained was selectively oxidized at the terminal double bond. The fifth ring was completed by a ""one-pot"" amidation-cyclization process promoted by palladium acetate. The final homochiral indolinocodeine (-)-31 was obtained in 16 steps and 3.6% overall yield from cyclohexan-1,3-dione.",10.1021/jo3014098,2012-09-11,0.5780385041288135
European Journal of Organic Chemistry,Stereoselective Total Syntheses of Paecilomycins E and F through a Protecting Group Directed Diastereoselective Intermolecular Nozaki–Hiyama–Kishi (NHK) Reaction,"Abstract An efficient and concise approach to the total syntheses of paecilomycins E ( 1 ) and F ( 2 ) is described. A protecting group directed intermolecular diastereoselective Nozaki–Hiyama–Kishi (NHK) reaction, a Julia–Kocienski olefination, a Sharpless asymmetric dihydroxylation, and De Brabander's lactonization protocol are used as the key steps.",10.1002/ejoc.201402133,2014-07-11,0.578037697264347
European Journal of Organic Chemistry,An Efficient Enantioselective Entry to the Piperidino-Quinolizidine Ring System of Lupine Alkaloids by Means of N-Acyliminium Ion Initiated Cyclization Reactions,"An efficient methodology for the enantioselective synthesis of the decahydro-1,5-methano-pyrido[1,2-a][1,5]diazocine skeleton found in tricyclic lupine alkaloids is described, starting from 3,5-disubstituted piperidines as chiral building blocks. Alkyne- or vinylsilane-terminated N-acyliminium ion cyclizations performed on appropriate 3,7-diazabicyclo[3.3.1]nonane derivatives allow for the highly stereoselective construction of piperidino-quinolizidine ring systems. A preliminary application of this methodology results in the synthesis of the quinolizidine alkaloid virgilidone.",10.1002/1099-0690(200104)2001:7<1377::aid-ejoc1377>3.3.co;2-6,2001-04-01,0.5780375385121678
European Journal of Organic Chemistry,An Efficient Enantioselective Entry to the Piperidino-Quinolizidine Ring System of Lupine Alkaloids by Means of N-Acyliminium Ion Initiated Cyclization Reactions,"An efficient methodology for the enantioselective synthesis of the decahydro-1,5-methano-pyrido[1,2-a][1,5]diazocine skeleton found in tricyclic lupine alkaloids is described, starting from 3,5-disubstituted piperidines as chiral building blocks. Alkyne- or vinylsilane-terminated N-acyliminium ion cyclizations performed on appropriate 3,7-diazabicyclo[3.3.1]nonane derivatives allow for the highly stereoselective construction of piperidino-quinolizidine ring systems. A preliminary application of this methodology results in the synthesis of the quinolizidine alkaloid virgilidone.",10.1002/1099-0690(200104)2001:7<1377::aid-ejoc1377>3.0.co;2-f,2001-04-01,0.5780375385121678
Tetrahedron,Diastereo- and enantioselective synthesis of a conagenin skeletal amide moiety,,10.1016/j.tetlet.2004.03.062,2004-04-01,0.5780331113234961
Organic Letters,Concise Synthesis of<i>v</i>-Coelenterazines,"A novel synthetic method for v-coelenterazine (v-CTZ), which is a vinylene-bridged analog of native CTZ with a large red-shifted luminescence property, is described. The synthesis was achieved in a concise way through the use of three sequential cross-coupling reactions and ring-closing metathesis (RCM). A newly synthesized C2-modified trifluoromethyl analog cf3-v-CTZ showed slightly more red-shifted luminescence than v-CTZ when it was used as a substrate for Renilla luciferases.",10.1021/acs.orglett.5b01872,2015-07-21,0.5780318151466683
Synthesis,A Total Synthesis of 1-Methoxycanthin-6-one: An Efficient One-Pot Synthesis of the Canthin-6-one Skeleton from β-Carboline-1-carbaldehyde,"A total synthesis of naturally occurring 1-methoxycan-thin-6-one is described. In this synthesis, we achieved one-pot conversion from β-carboline-1-carbaldehyde to the canthin-6-one skeleton by the sequential addition of lithium ketene acetal in LiHMDS solution followed by the addition of EtOH in the reaction mixture.",10.1055/s-2004-834915,2004-11-17,0.5780313084139634
Synthesis,Synthesis of (-)-LL-C10037α and Related Manumycin-Type Epoxyquinols,"All articles of this category Starting with N -allyloxycarbonyl-protected 2,5-dimethoxyaniline, hypervalent iodine oxidation protocols and selective enone epoxidation provides the Streptomyces metabolite LL-C10037 α in nine steps and 7-10% overall yield. In an asymmetric variant of this strategy, ( R,R )-pentane-2,4-diol is used as a chiral acetalization agent. The resulting semiquinone spiroacetal, due to an ortho -acylamino substituent that restricts the 1,3-dioxane ring conformation, undergoes face-selective epoxidation and is further functionalized to give (-)-LL-C10037 α in 94% ee. These pathways represent the first syntheses of the highly functionalized m C 7 N core of the manumycins and have been further extended toward the preparation of analogs for SAR studies of this class of antitumor antibiotics. Manumycins inhibit the farnesylation of Ras-protein by PFTase (protein farnesyltransferase). hypervalent iodine oxidation - face-selective enone epoxidation - chiral quinone monoketals - antitumor antibiotics",10.1055/s-1995-4141,1995-12-01,0.5780303754452315
Synthesis,"Studies on Selective Preparation of Aromatic Compounds; 17. A New Route for the Preparation of 10,11-Dihydro-5<i>H</i>-dibenzo[<i>a</i>,<i>d</i>]cycloheptene",,10.1055/s-1978-24711,1978-01-01,0.5780296369471288
Synlett,Chiral Cyclodimerization Reactions: Construction of Nonnatural Dimeric Carbazoles from (±)-4-Methylene-3-hydroxytetrahydrocarbazoles,"Abstract In this Synpacts article, we describe the concept of cyclodimerization in the biosynthesis and biomimetic synthesis of natural products and unnatural products. We also discuss key details of our discovery and development of a biomimetic-like, selective, homo- and heterochiral cyclodimerization strategy for the construction of nonnatural dimeric carbazole frameworks by employing a formal [3+2] annulation. Our work also demonstrated a novel reactivity of 1-(indol-2-yl)pent-4-yn-3-ols, and their potential as new synthetic building blocks in organic synthesis. 1 Introduction: Chiral Cyclodimerization Reactions 2 Biomimetic Syntheses of Natural Products through Chiral Cyclodimerizations 3 Bioinspired Synthesis of Nonnatural Dimeric Carbazoles through Selective Chiral Cyclodimerizations 4 Future Perspectives and Conclusions",10.1055/a-2192-9235,2023-10-16,0.5780288501780944
Journal of Organic Chemistry,"Diaryl-Substituted (Dihydro)pyrrolo[3,2,1-<i>hi</i>]indoles, a Class of Potent COX-2 Inhibitors with Tricyclic Core Structure","A new compound class of diaryl-substituted heterocycles with tricyclic dihydropyrrolo[3,2,1-hi]indole and pyrrolo[3,2,1-hi]indole core structures has been designed and was synthesized by a modular sequence of Friedel-Crafts acylation, amide formation, and McMurry cyclization. This synthesis route represents a novel and versatile access toward dihydropyrrolo[3,2,1-hi]indoles and is characterized by good chemical yields and high modularity. From a set of 19 derivatives, 11 candidates were selected for determination of their COX inhibition potency and were found to be selective inhibitors with high affinity to COX-2 (IC50 ranging from 20-2500 nM and negligible inhibition of COX-1). The binding mode of the novel inhibitors in the active side of COX-2 was calculated in silico using the protein-ligand docking program GOLD by application of the molecular structures of two compounds derived from X-ray crystallography. Two novel compounds with high affinity to COX-2 (6k = 70 nM, 8e = 60 nM) have a fluoro substituent, making them promising candidates for the development of (18)F-radiolabeled COX-2 inhibitors for imaging purposes with positron emission tomography (PET).",10.1021/acs.joc.5b00537,2015-04-24,0.5780247402765493
Chemical Science,Formal synthesis of kibdelomycin and derivatisation of amycolose glycosides,"A new formal synthesis gave kibdelomycin with 2.8% yield over 19 steps, featuring a general method for introduction of a 3-(α-aminoalkyl) linkage into glycosides, and the first N -glycosylation of 3-acyltetramic acids.",10.1039/d3sc00595j,2023-01-01,0.5780243602719601
Tetrahedron,Synthesis of the hexahydronaphthalene moiety of (+)-mevinolin,,10.1016/s0040-4039(00)94513-1,1983-01-01,0.5780207825622081
Tetrahedron,Synthesis of the polyketide moiety of the jamaicamides,,10.1016/j.tetlet.2015.10.069,2015-10-25,0.5780207825622081
Tetrahedron,A stereocontrolled synthesis of the hydrophobic moiety of rhamnolipids,,10.1016/j.tetlet.2015.01.091,2015-01-19,0.5780207825622081
Tetrahedron,The synthesis of the monomeric moiety of disorazole C1,,10.1016/s0040-4039(00)00271-9,2000-04-01,0.5780207825622081
Organic Letters,A Convergent Synthesis of the C1−C16 Segment of Goniodomin A via Palladium-Catalyzed Organostannane−Thioester Coupling,"A convergent synthesis of the C1-C16 segment of goniodomin A, an actin-targeting marine polyether macrolide natural product, has been achieved via a 2-fold application of palladium-catalyzed organostannane-thioester coupling.",10.1021/ol1031409,2011-02-10,0.5780207517711328
Tetrahedron,"Stereoselective Synthesis of (R)-(−)-2,2-Dimethyl-3-t-butoxycarbonyl-4-ethynyl-oxazolidine: a Chiral Building Block for the Synthesis of a New Class of Substituted Alkynes",,10.1016/00404-0399(50)1725w-,1995-11-06,0.5780172978908048
Tetrahedron,"Stereoselective synthesis of (R)-(−)-2,2-dimethyl-3-t-butoxycarbonyl-4-ethynyl-oxazolidine: a chiral building block for the synthesis of a new class of substituted alkynes",,10.1016/0040-4039(95)01725-w,1995-11-01,0.5780172978908048
Tetrahedron,Novel synthetic equivalents of differentially protected tartaric aldehydes. A simple route to useful c-4 chiral synthons.,,10.1016/s0040-4039(00)82295-9,1988-01-01,0.578011828062224
Journal of the American Chemical Society,"Short, Enantioselective Total Synthesis of (+)-Ineleganolide","High Resolution Image Download MS PowerPoint Slide Owing to their distinctive polycyclic architectures and promising bioactivities, the large family of furanocembranoid natural products continues to attract significant attention from the synthetic community. Herein, we present a 10-step total synthesis of (+)-ineleganolide, a highly oxidized norcembranoid natural product featuring a synthetically challenging caged pentacyclic framework. An interesting trans -selective photochemical [2 + 2] cycloaddition involving an unusual α,β -unsaturated tricarbonyl chromophore was used to generate a strained cyclobutanol which underwent a C–C bond cleavage cascade when exposed to Brønsted acid. Through this sequence, the ineleganolide core polycycle was generated in only six steps from commercially available materials. This strategy provides a conceptually new abiotic blueprint for this fascinating family of diterpenes.",10.1021/jacs.5c17640,2025-11-21,0.578011766479682
Synthesis,An Asymmetric Synthesis of Rosuvastatin Calcium,"A novel asymmetric synthesis of a (3 R ,5 S )-dihydroxyhexanoic ester is described. The ester, which serves as the precursor for generating the side chain of rosuvastatin, is synthesized from d -glucose and subsequently coupled, under Wittig olefination conditions, with a phosphonium ylide derived from an appropriately substituted pyrimidine moiety. The coupling results in the formation of a precursor containing all the structural features of rosuvastatin. This precursor is converted into rosuvastatin calcium following a well-established procedure.",10.1055/s-0035-1562787,2016-08-16,0.5780113508892798
Tetrahedron,A novel and efficient synthesis of (+)- and (−)-trans-2-aminocyclohexanol by enzymatic hydrolysis,,10.1016/s0040-4039(00)82073-0,1988-01-01,0.5780113462483869
Organic Letters,Synthesis of 3-Aminochroman Derivatives by Radical Cyclization,"[reaction: see text] Enantiomerically pure 5-acetyl-3-amino-3,4-dihydro-2H-1-benzopyran and methyl 3-amino-3,4-dihydro-2H-1-benzopyran-5-carboxylate were successfully synthesized starting from d- or l-serine. The formation of the benzopyran ring involved a radical cyclization step. The enantiomeric purities of the final aminochroman derivatives were determined by capillary electrophoresis using beta-cyclodextrins as a chiral selector.",10.1021/ol0353215,2003-10-16,0.5780099329588032
Angewandte Chemie International Edition,Total Synthesis of Isoxeniolide A**,"Isoxeniolide A is a highly strained xenicane diterpenoid of marine origin. This natural product is representative for a subfamily of xenicanes incorporating an allylic hydroxy group in the nine-membered ring; members of this xenicane subfamily so far have not been targeted by total synthesis. Herein, we describe the first asymmetric total synthesis of isoxeniolide A. Key to forming the challenging E-configured cyclononene ring was a diastereoselective intramolecular Nozaki-Hiyama-Kishi reaction. Other important transformations include an enzymatic desymmetrization for absolute stereocontrol, a diastereoselective cuprate addition and the use of a bifunctional vinyl silane building block. Our strategy also permits access to the enantiomer of the natural product and holds potential to access a multitude of xenicane natural products and analogs for structure-activity relationship studies.",10.1002/anie.202315423,2023-12-20,0.5780078730526935
Tetrahedron,Synthesis of a new pseudopeptidoleukotriene : The first LTD4 analogue with potent agonist activity,,10.1016/s0040-4039(00)78798-3,1991-06-01,0.5780068380816931
Angewandte Chemie International Edition,Transformation of Methane to Propylene: A Two‐Step Reaction Route Catalyzed by Modified CeO<sub>2</sub> Nanocrystals and Zeolites,"Propylene from methane: The transformation of methane to propylene has been realized in a two-step route via CH3Cl or CH3Br. CeO2 serves as an efficient and stable catalyst for the oxidative chlorination and bromination of methane to CH3Cl and CH3Br. In the second step, a modified zeolite is highly a selective and stable catalyst for the conversion of CH3Cl or CH3Br into propylene.",10.1002/anie.201104071,2012-01-24,0.5780005303857164
Organic Process Research & Development,A New Synthesis and Process Development of Bis(fluoroalkyl)pyrazoles As Novel Agrophores,"The synthesis of 3,5-bis(fluoroalkyl)-pyrazoles as novel agrophores is described. Commercially available fluoroacetoacetates are treated with BF 3 -activated TFEDMA affording in a straightforward one-pot sequence pyrazole carboxylates in good yields and with excellent regioselectivity. The carboxylate intermediates have been converted into the corresponding pyrazolic acids and submitted to decarboxylation, affording valuable building blocks for the design of novel bioactive ingredients. The found process is suitable for scale up and preparation of compounds in kilogram quantity.",10.1021/op500102h,2014-04-15,0.5779922462403748
Journal of Organic Chemistry,Stereoselective Synthesis of the Cytotoxic 14-Membered Macrolide Aspergillide A,"A stereoselective synthesis of the cytotoxic 14-membered macrolide aspergillide A has been performed. The preparation of a cis-2,6-disubstituted tetrahydropyran ring via stereoselective reduction of an intermediate cyclic hemiacetal was one key feature of the synthesis. The macrocyclic lactone ring was created by means of a ring-closing metathesis (RCM), whereby the new C=C bond displayed exclusively the undesired Z configuration. Conversion to the required E configuration was achieved via photochemical isomerization.",10.1021/jo9027038,2010-02-09,0.5779900194708505
Organic Letters,A Novel Route to Preussomerins via 2-Arylacetal Anions,"[reaction--see text] Dimerization of salicylaldehydes provided 6H,12H-6,12-epoxydibenzo[b, f][1,5]dioxocins in multigram quantities. Deprotonation-allylation of the benzylic acetals followed by further functionalization of the diallyl derivative and double Friedel-Crafts cyclization gave a novel preussomerin analogue which possessed the full carbon skeleton of the natural products.",10.1021/ol005881t,2000-05-02,0.5779899762508446
Tetrahedron,Synthesis of new chiral phosphinephosphites having 2-diphenylphosphinobiphenyl-2′-yl backbone and their use in Rh(I)-catalyzed asymmetric hydroformylations,,10.1016/s0040-4039(00)73039-5,1994-03-01,0.5779867340377601
Organic Letters,Lactone-Facilitated Chemoenzymatic Synthesis of Sulfoglucuronosyl Paragloboside Oligosaccharides Bearing the HNK-1 Epitope,"Herein, we describe a lactone-facilitated chemoenzymatic strategy for the synthesis of sulfoglucuronosyl paragloboside pentasaccharide, sulfoglucuronosyl lactosaminylparagloboside heptasaccharide, and their nonsulfated derivatives. The approach involves the efficient enzymatic modular assembly (EMA) of the nonsulfated paragloboside backbones, followed by highly regioselective chemical manipulation steps that introduce a sulfate group at the C3 position of glucuronic acid through the formation of a C6,3-lactone intermediate.",10.1021/acs.orglett.5c04620,2025-12-08,0.5779856919318136
Tetrahedron,"The preparation of α-substituted, β-hydroxy piperidines and pyrrolidines: The total synthesis of febrifugine",,10.1016/0040-4039(96)00527-8,1996-05-01,0.577980215188251
Journal of Organic Chemistry,Synthesis of Protected Amino Hexitol Nucleosides as Building Blocks for Oligonucleotide Synthesis,"A new synthesis protocol for the preparation of hitherto unknown 1′,5′-anhydro-4′-amino-trityl/MMTr hexitol nucleosides has been developed. Key steps in the synthesis of the pyrimidine analogues (U and C) include the regioselective d - allo -hexitol oxirane and 2′,4′-anhydronucleoside ring opening by uracil and azide, respectively. A different strategy using a regioselective epoxide ring opening of d - gulo -oxirane, followed by a S N 2 type of azidation reaction, has been adopted for the purine analogues (A and G). These compounds can be easily converted to 6′-phosphoramidites for the solid-phase synthesis of N4′ → P6′ phosphoramidates of amino hexitol nucleic acids (AHNA).",10.1021/acs.joc.8b02444,2018-12-07,0.5779788010119207
Tetrahedron,Vectorised transport of drugs: Synthesis of a new glycosyl derivative of β-cyclodextrin.,,10.1016/0040-4039(92)88052-7,1992-01-01,0.5779783979935669
Tetrahedron,Synthesis of a new series of potent inhibitors of thromboxane A2 biosynthesis,,10.1016/s0040-4039(00)86251-6,1983-01-01,0.5779768774936168
Tetrahedron,Synthesis and mesomorphic behaviour of new mesogenic compounds possessing a cholesteryl ester moiety connected to a pyrimidine core,,10.1016/j.tetlet.2009.02.065,2009-02-15,0.5779742194533275
European Journal of Organic Chemistry,A Convergent Hetero‐Diels–Alder Strategy for Asymmetric Access to a Lactone Containing Two Lipidic Chains,"Abstract Eu(fod) 3 ‐catalyzed heterocycloaddition of chiral β‐alkyl‐ N ‐vinyl‐1,3‐oxazolidin‐2‐ones with a heterodiene bearing a lipidic chain led to heterocycloadducts in high yield with excellent endo and facial selectivities. An original lipidic lactone, a potent precursor of a ceramide analog, was obtained in seven steps from the adduct in a convergent manner after appropriate functionalization.",10.1002/ejoc.201200513,2012-05-31,0.5779719663565477
Journal of the American Chemical Society,"Asymmetric Synthesis and Biological Evaluation of Platensilin, Platensimycin, Platencin, and Their Analogs via a Bioinspired Skeletal Reconstruction Approach","Platensilin, platensimycin, and platencin are potent inhibitors of β-ketoacyl–acyl carrier protein synthase (FabF) in the bacterial and mammalian fatty acid synthesis system, presenting promising drug leads for both antibacterial and antidiabetic therapies. Herein, a bioinspired skeleton reconstruction approach is reported, which enables the unified synthesis of these three natural FabF inhibitors and their skeletally diverse analogs, all stemming from a common ent -pimarane core. The synthesis features a diastereoselective biocatalytic reduction and an intermolecular Diels–Alder reaction to prepare the common ent -pimarane core. From this intermediate, stereoselective Mn-catalyzed hydrogen atom–transfer hydrogenation and subsequent Cu-catalyzed carbenoid C–H insertion afford platensilin. Furthermore, the intramolecular Diels–Alder reaction succeeded by regioselective ring opening of the newly formed cyclopropane enables the construction of the bicyclo[3.2.1]-octane and bicyclo[2.2.2]-octane ring systems of platensimycin and platencin, respectively. This skeletal reconstruction approach of the ent -pimarane core facilitates the preparation of analogs bearing different polycyclic scaffolds. Among these analogs, the previously unexplored cyclopropyl analog 47 exhibits improved antibacterial activity (MIC 80 = 0.0625 μg/mL) against S. aureus compared to platensimycin.",10.1021/jacs.4c02256,2024-07-08,0.5779719088921683
Journal of the American Chemical Society,"Total Synthesis of Thyrsiferyl 23-Acetate, a Specific Inhibitor of Protein Phosphatase 2A and an Anti-Leukemic Inducer of Apoptosis","A convergent synthetic entry to the squalenoid polyether system has been developed and applied to the biologically active marine natural products thyrsiferyl 23-acetate ( 1a ), thyrsiferol ( 1b ), thyrsiferyl 18-acetate ( 1c ), and thyrsiferyl 18,23-diacetate ( 1d ). This involved the separate construction of two advanced intermediates representing the C1−C15 ( 4 ) and C16−C24 ( 5 ) domains, followed by their organochromium-mediated coupling, installation of the tertiary alcohol at C15, and manipulation of the C18 and C23 acetate moieties. The C1−C15 ( 4 ) intermediate containing the three tetrahydropyranyl rings (A−B−C) was derived from two preconstructed tetrahydropyran-containing units representing the functionalized A (C2−C6) and C (C10−C14) rings ( 6 and 7, respectively). The bromotetrahydropyranyl A ring was obtained via bromoetherification of the hydroxyalkene 16, which was synthesized from (2 R,3 R )-epoxy geraniol. The C ring was stereoselectively constructed by acid-catalyzed opening of the hydroxy epoxide 32, derived from d -glutamic acid. Intermediates 6 and 7 were joined using organochromium conditions, and ketone and hydroxyl functionalities were installed at carbons 7 and 11, respectively. Closure of the B ring was accomplished stereoselectively by formation of species derived from a C7, C11 keto-alcohol and in situ reduction of a tetrahydropyranyl oxonium. The complementary tetrahydrofuran D (C19−C22) ring was obtained from a geraniol-derived tertiary hydroxy alkene ( 44 ) via a stereoselective Re(VII)-induced syn -oxidative cyclization. The side chain appended to the D ring was elaborated into trans -alkenyl iodide 5 under Takai reaction conditions. CrCl 2 -mediated coupling of aldehyde 4, containing the secondary bromide at C3 of the natural products, with iodide 5 bearing acetate moieties at C18 and C23, installed the C15−C16 carbon−carbon bond. The resultant C15 allylic carbinol was converted into an α,β-saturated ketone, and the final methyl group was added stereoselectively using methylmagnesium bromide. Saponification of the C18 acetate yielded 1a, whereas cleavage of both C18 and C23 acetates gave the triol 1b . This modular entry into the squalenoid−polyether system may facilitate further evaluation of the antileukemic, apoptosis-inducing, protein serine/threonine phosphatase 2A inhibitory and anti-multidrug resistance activities of the thyrsiferol-derived natural products.",10.1021/ja000001r,2000-09-01,0.5779709428055559
Synlett,"Stereoselective Approach for the Synthesis of 2-epi-Hyacinthacine A2, (–)-7a-epi-Hyacinthacine A1, 1-Deoxy-d-altro-homonojirimycin, and Some Pyrrolidine Iminosugars",A divergent approach has been developed for the synthesis of some important iminosugars by stereoselective allylation of the lyxosylamine derived from d -lyxose and intramolecular 5- exo -tet ring opening of the epoxide. The strategy described in this paper will be useful for the synthesis of some other biologically active iminosugars for the drug-discovery program.,10.1055/s-0035-1562782,2016-07-19,0.5779694023350278
Tetrahedron,A synthetic approach to taxane diterpenes. A synthesis of the bicyclo[5.3.1]undecenone ring system,,10.1016/s0040-4039(00)83977-5,1986-01-01,0.5779685111064118
Tetrahedron,Erythromycin as a supramolecular receptor,,10.1016/s0040-4039(00)86665-4,1988-01-01,0.577961644214178
Tetrahedron,A self-complexing macrocycle acting as a chromophoric receptor,,10.1016/s0040-4039(97)00688-6,1997-05-01,0.577961644214178
Tetrahedron,Oxoanion recognition by a thiouronium receptor,,10.1016/s0040-4039(98)01806-1,1998-10-01,0.577961644214178
European Journal of Organic Chemistry,Stereoselective Synthesis of (–)‐α‐Conhydrine and Its Pyrrolidine Analogue,"Abstract The stereoselective synthesis of (–)‐α‐conhydrine and its pyrrolidine analogue was achieved from readily available D ‐erythronolactone. The key step of this synthesis includes a highly regioselective and diastereoselective addition of chlorosulfonyl isocyanate to 1,2‐ anti ‐dibenzyl ether to afford the 1,2‐ anti ‐amino alcohol.",10.1002/ejoc.201200489,2012-06-20,0.5779616123722714
Journal of Organic Chemistry,"Novel Bicyclic Lactams as XaaPro Type VI β Turn Mimics:  Design, Synthesis, and Evaluation","The design, enantioselective synthesis, and structural characterization of novel bicyclic lactams as peptide mimics of the type VI beta turn is described. The mimics duplicate the conformation of the backbone and disposition of the side-chain atoms of the central two residues of the turn. The Gly L-Pro mimic, lactam 6, was prepared in good overall yield starting from (S)-2-(2'-propenyl)proline. (1)H NMR spectroscopy defined the relative stereochemistry of the substituents and conformational characteristics of the six-membered ring of the lactam; X-ray crystallographic analysis confirmed the conformational and stereochemical assignment. Examination of the crystal structure of lactam 6 revealed that the central amide bond was twisted appreciably out of planarity. The twisting of the amide bond was attributed to angle strain resulting from the presence of the sp(2)-hybridized nitrogen atom at the junction of the two rings. Alkylation of the enolate of the N,N-dimethylformamidine derivative of lactam 6 with benzyl bromide afforded stereoselectively the formamidine 11, a mimic of an L-Phe L-Pro dipeptide in the type VI turn conformation. The efficient synthetic route to highly functionalized peptidomimetics such as 11 will prove highly useful in peptide structure-function studies.",10.1021/jo960012w,1996-01-01,0.5779614904643285
Journal of Organic Chemistry,New Strategy for the Construction of Epoxy-Bridged Tetrahydropyran Frameworks from Trioxane Precursors: Application to a Concise Synthesis of a Riesling Acetal,"A simple one-pot method to prepare dioxabicyclo[2.2.1] heptane derivatives, from readily available 1,2,4-trioxane frameworks, under catalytic hydrogenation conditions over a platinum surface is reported. The overall transformation involves the hydrogenation of the double bond and a ring contraction rearrangement that presumably proceeds via a hydrogenolytic cleavage of the O-O bond and subsequent intramolecular ketalization. The strategy was successfully applied to the synthesis of a Riesling acetal.",10.1021/jo8017928,2008-10-10,0.5779583164050478
Tetrahedron,The first total synthesis of the 6-hydroxy-4E-sphingenines,,10.1016/s0040-4039(03)00390-3,2003-03-01,0.577951665516817
Tetrahedron,Total synthesis of a 1α-hydroxy-1-carbacephem,,10.1016/s0040-4039(00)94534-9,1983-01-01,0.577951665516817
Organic Letters,Total Synthesis of (−)-Aspidospermine via Diastereoselective Ring-Closing Olefin Metathesis,"An enantiocontrolled total synthesis of (-)-aspidospermine has been achieved. The key element of the strategy is the diastereoselective construction of the quaternary stereogenic center employing 1,4-asymmetric induction during the ring-closing olefin metathesis.",10.1021/ol034020s,2003-02-01,0.5779512566994226
European Journal of Organic Chemistry,Electrophile‐Induced Cyclization of 3‐Alkynyl‐2‐arylquinoxalines: A Method for Benzo‐ and Naphthophenazine Synthesis,"A facile synthesis of benzo[ a ]‐, naphtho[1,2‐ a ]‐ and naphtho[2,1‐ a ]phenazines by ICl‐promoted 6‐ endo ‐ dig cyclization of 3‐alkynyl‐2‐arylquinoxalines has been developed. The starting 3‐alkynyl‐2‐arylquinoxalines were synthesized from 2,3‐dichloroquinoxaline by two successive Sonogashira and Suzuki–Miyaura reactions. The method works well for 3‐alkynyl‐2‐arylquinoxalines bearing various functional groups at the alkyne moiety. The arrangement and nature of the substituent in the 2‐aryl fragment affect the regioselectivity of the cyclization. For the substrate of one particular type, namely 2‐(4‐methoxyphenyl)‐3‐( p ‐tolylethynyl)quinoxaline, the treatment with ICl leads to the alternative 5‐ endo ‐ dig cyclization followed by demethylation of the methoxy group to give a spirocyclohexadienone derivative.",10.1002/ejoc.201600660,2016-08-01,0.5779503319571565
Synlett,A Multicomponent Coupling Strategy for the Synthesis of the Triene Component of the Oxazolomycin Antibiotics,"Concise and versatile routes suitable for the synthesis of three geometric isomers of an analogue of the left hand triene sub-unit of oxazolomycin are reported, using a Stille coupling strategy.",10.1055/s-2002-34905,2002-01-01,0.5779447377421443
Journal of Organic Chemistry,Enantiospecific Total Synthesis and Absolute Configuration Assignment of Chabrolobenzoquinone H,"), a meroditerpene metabolite with cytotoxic activity, is synthesized via a stereoselective Julia-Kocienski olefination between a chiral pool derived aliphatic PT-sulfone and a benzoquinone aldehyde partner. The latter was obtained via consecutive chain extension steps involving a Stille coupling and a stereospecific olefin cross-metathesis reaction followed by malonic ester synthesis and a Krapcho decarboxylation. Furthermore, this total synthesis securely determined the absolute configuration of the targeted natural product.",10.1021/acs.joc.1c02634,2021-12-22,0.5779441258244299
Organic Letters,Total Synthesis of (−)-Stemonine,[reaction: see text] An enantioselective total synthesis of (-)-stemonine (1) is reported via a convergent assembly of the acyclic precursor 2. Key transformations include a Staudinger-aza-Wittig reaction to form the central perhydroazepine ring system and an iodine-induced tandem cyclization to construct the pyrrolidino-butyrolactone framework.,10.1021/ol035368q,2003-08-13,0.5779425487461881
Journal of the American Chemical Society,Directed Electrophilic Cyclizations:  Efficient Methodology for the Synthesis of Fused Polycyclic Aromatics,"A versatile method for the synthesis of complex, fused polycyclic aromatic systems in high chemical yield is described. Construction is achieved using a general two-step synthetic sequence. Pd-catalyzed Suzuki and Negishi type cross-coupling chemistries allow for the preparation of nonfused skeletal ring systems in yields consistently >80%. The critical ring-forming step, which generally proceeds in very high to quantitative yield, utilizes 4-alkoxyphenylethynyl groups and is induced by strong electrophiles such as trifluoroacetic acid and iodonium tetrafluoroborate. The reaction in essence produces phenanthrene moieties which are integrated into extended polycyclic aromatic structures. Fused polycyclic benzenoids as well as benzenoid/thiophene systems may be prepared utilizing this methodology. The scope of the described cross-coupling/cyclization chemistry including mechanistic insights and problematic side reactions are described.",10.1021/ja9642673,1997-05-01,0.5779416892753771
Organic Letters,Diastereoselective One-Pot Synthesis of 7- and 8-Substituted 5-PhenylmorphansProbes for Narcotic Receptor Mediated Phenomena. 45.,"Novel 7- and 8-alkyl and aryl substituted 5-phenylmorphans were synthesized from substituted allyl halides and N-benzyl-4-aryl-1,2,3,6-tetrahydropyridine by a highly efficient and diastereoselective reaction series, ""one-pot"" alkylation and ene-imine cyclization followed by sodium borohydride reduction. Mild cyclization conditions gave the desired substituted 5-phenylmorphans in good yield as a single diastereomer.",10.1021/ol2021862,2011-09-12,0.5779352338416248
Organic Letters,"Construction of a C(30−38) Dioxabicyclo[3.2.1]octane Subtarget for (+)-Sorangicin A, Exploiting a Regio- and Stereocontrolled Acid-Catalyzed Epoxide Ring Opening","[reaction: see text] In this paper, we report assembly of the novel dioxabicyclo[3.2.1]octane subtarget (-)-2, comprising the signature structural element of the potent antibiotic (+)-sorangicin A (1). The synthesis was achieved in 15 steps (1.5% overall yield) via a series of acid-catalyzed epoxide ring openings. The first, facilitated by the complex of alkyne (+)-3 with Co(2)(CO)(8), proceeded in a highly regio- and stereoselective fashion.",10.1021/ol049644s,2004-03-30,0.5779346717128003
Organic Letters,Synthesis of a Chiral Aziridine Derivative as a Versatile Intermediate for HIV Protease Inhibitors,"[reaction: see text] Chiral aziridine derivative 1 was prepared from D-tartaric acid. This compound could be utilized as a common intermediate for the synthesis of hydroxyethylamine class HIV protease inhibitors such as saquinavir, amprenavir, or nelfinavir.",10.1021/ol016147s,2001-06-29,0.5779274524367601
Organic Letters,Enantioselective Pathway for the Synthesis of Laurenditerpenol,Simple enantioselective routes to the two key intermediates shown above (at center) for the synthesis of laurenditerpenol have been developed using a Diels-Alder step and the same catalyst system for each.,10.1021/ol1004802,2010-03-25,0.5779251032886294
Synthesis,"A Reliable Route to 1,2-Diamino-4,5-phthalodinitrile","Starting from o-phenylenediamine, we have developed a new and reliable route to 1,2-diamino-4,5-phthalodinitrile that is based on the reductive desulfurisation of 5,6-dicyano-2,1,3-benzothiadiazole with sodium borohydride. The reaction sequence uses only cheap reagents and relies on simple recrystallisations for the purification of all intermediates.",10.1055/s-2008-1042939,2008-04-01,0.5779222213057481
Tetrahedron,A one-step ester to hydrocarbon reduction,,10.1016/s0040-4039(01)87351-2,1973-01-01,0.5779202948636386
Tetrahedron,"An expeditious synthesis of (2R,3S)-3-tert-butoxycarbonylamino-1-isobutylamino-4-phenyl-2-butanol, a key building block of HIV protease inhibitors",,10.1016/s0040-4039(96)02406-9,1997-01-01,0.5779157026295382
European Journal of Organic Chemistry,"Studies towards the Total Synthesis of (–)‐Caulerpenynol, a Toxic Sesquiterpenoid of the Green Seaweed <i>Caulerpa taxifolia</i>","Abstract The first diastereoselective synthesis of the antimicrobial and cytotoxic agent (–)‐caulerpenynol ( 2 ) was achieved in relatively few steps from commercially available ( S )‐malic acid. Highlights of this synthesis include the nonracemization of the sensitive α‐hydroxy ketone moiety and the proper choice of the protecting groups for critical last deprotection step. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2009)",10.1002/ejoc.200900101,2009-05-07,0.5779124575212564
Tetrahedron,"Synthetic studies on polyoxypeptins: stereoselective synthesis of (2S,3R)-3-hydroxy-3-methylproline using SmI2-mediated cyclization",,10.1016/s0040-4039(02)00833-x,2002-05-01,0.5779082000433069
Organic Process Research & Development,A Short Review on the Synthetic Routes for the Antiepileptic Drug (<i>S</i>)-Levetiracetam,Epilepsy is a chronic disorder characterized by recurrent unpredictable seizures. Levetiracetam (Keppra) was introduced by UCB for the treatment of partial onset seizures in patients above 16 years of age diagnosed with epilepsy. This review reports synthetic strategies available for the synthesis of ( S )-levetiracetam and will certainly aid the quest for the development of new routes for its synthesis.,10.1021/acs.oprd.4c00002,2024-03-23,0.5779058134665808
Organic Letters,Concise Synthesis of (±)-Cytisine via Lithiation of <i>N</i>-Boc-bispidine,"[reaction: see text] (+/-)-Cytisine has been synthesized in 19% overall yield via a six-step approach from commercially available materials. Key features of this new strategy are as follows: (i) initial construction of the bispidine core, (ii) lithiation-transmetalation-allylation of an N-Boc-bispidine, and (iii) a Pd/C-mediated dihydropyridone oxidation-N-debenzylation process.",10.1021/ol0516869,2005-08-27,0.5779041581298979
European Journal of Organic Chemistry,First Total Synthesis of the Benzotropolone/Bis(pulvinone) Natural Product Aurantricholone Exploiting New Strategies for Establishing Benzotropolones and <i>Z</i>‐Configured Pulvinones,"Abstract Aurantricholone as well as its calcium and lithium salts, all of which represent the coloring principle of the fungus Tricholoma aurantium , were synthesized for the first time, namely in 15 steps, 10 of which were our longest linear sequence. We developed an access to benzotropolones after dibromocyclopropanating alkyl or silyl enol ethers of 1‐tetralones. Successive treatments with DMAP‐ N ‐oxide and Ac 2 O effected ring‐enlargement, oxidation, and acetylation. O ‐acetyl‐1‐bromo‐3,4‐dimethoxybenzotropolone obtained thereby – similarly as unsubstituted benzotropolone – was brominated at C‐8 in two steps by adopting our recently published bromination protocol for otherwise unsubstituted O ‐acetylbenzotropolone. Thereafter, a double and doubly Z ‐selective Suzuki‐coupling with a newly introduced boronate established the O ‐methylated pulvinone moiety as well as the O ‐methylated “pulvinone‐like” motif of what altogether equaled the completed aurantricholone scaffold . Its deprotection (two steps) furnished the title compound either as its protonated form or its calcium or lithium salt.",10.1002/ejoc.202201120,2022-11-09,0.5779015803486063
Tetrahedron,"Amarusine A, a new dioxaspiro[4.4]nonane derivative with a butyrolactone ring from Pleioblastus amarus",,10.1016/j.tetlet.2014.04.031,2014-04-20,0.5779013432841731
Tetrahedron,Highly stereoselective synthesis of non-racemic 3-substituted dihydro-benzo[de]isoquinolinones via an addition-cyclization-substitution method,"Substituted dihydrobenzo[de]isoquinolinones were synthesized via diastereoselective addition of Grignard reagents to the N-tert-butylsulfinylimine derived from 1,8-naphthaldehydic methyl ester, followed by cyclization and substitution at the sulfur atom. The products were obtained in 25–98% yield and with enantiomeric excess of 46–99%.",10.1016/j.tetlet.2020.152034,2020-05-15,0.5778966676078906
Organic Letters,"Efficient Fragment Coupling Approaches toward Large Oxacalix[<i>n</i>]arenes (<i>n</i> = 6, 8)","The first rational, stepwise synthesis of enlarged oxacalix[n]arenes (n > 4) is described. Variously substituted oxacalix[3]arene[3]pyrimidines were prepared rather selectively by a straightforward [3 + 3] fragment coupling approach after a thorough search for the optimum nucleophilic aromatic substitution conditions. Similar procedures also allowed facile synthesis of unsymmetrical oxacalix[4]- and oxacalix[8]arenes.",10.1021/ol900116h,2009-03-19,0.5778962799067783
Tetrahedron,Selective cleaving the N P bond of difluoromethylene phosphabetaines for effective synthesis of β-ketoamides,,10.1016/j.tetlet.2019.06.036,2019-06-20,0.5778948086287754
Angewandte Chemie International Edition,Cascade Palladium‐Catalyzed Direct Intramolecular Arylation/Alkene Isomerization Sequences: Synthesis of Indoles and Benzofurans,"One route, two cycles: A palladium-catalyzed intramolecular direct arylation reaction combined with an isomerization step provided a straightforward synthetic route to both indoles and benzofurans (see scheme). Isolation and functionalization of intermediate alkene isomers allowed the formation of variants having substituents remote from the core.",10.1002/anie.201004097,2010-09-13,0.577891569140907
Journal of Organic Chemistry,"Convergent Access to Polycyclic Cyclopentanoids from α,β-Unsaturated Acid Chlorides and Alkynes through a Reductive Coupling, Nazarov Cyclization Sequence","Reductive coupling of α,β-unsaturated acid chlorides A with alkynoyls B provides convergent access to Nazarov cyclization precursors, α-carboxy divinyl ketones C. Cyclization of C gives an intermediate oxyallyl cation intermediate D, which can be trapped with tethered arenes (Ar). The resultant products can be further cyclized through nucleophilic displacement of suitable leaving groups X by tethered OH groups to give lactones (in a subsequent step). Where X is a suitable chiral auxiliary (e.g., oxazolidinone) this strategy affords access to homochiral cyclopentanoids.",10.1021/jo500040b,2014-03-28,0.5778836548271974
Journal of the American Chemical Society,Effective Combination of Two-Directional Synthesis and Rhenium(VII) Chemistry:  Total Synthesis of meso Polyether Teurilene,"The efficient total synthesis of the cytotoxic meso polyether teurilene ( 1 ), rarely occurring in nature, has been achieved through the effective combination of the concept of two-directional synthesis and the rapidly progressing rhenium(VII) chemistry. In the key rhenium(VII)-promoted syn oxidative cyclization reaction of the two-directional substrate 3, trans-syn diastereoselectivity (steric control) has been observed in contrast to our previous observation of cis-syn diastereoselectivities (chelation control) for bishomoallylic tertiary alcohols possessing the neighboring tetrahydrofuran (THF) ring. This synthesis in only 10 steps from commercially available methyl tiglate is significantly shorter than the previous one requiring 25 steps as reported by Shirahama et al.",10.1021/ja990154i,1999-07-01,0.5778832539650606
Organic Letters,Synthesis of 1-Aryltetralins and 1-Arylnaphthalenes via (4 + 2) Annulation of β-Ketosulfones with Styryl Bromides,"A novel route has been developed for the synthesis of various substituted 1-aryltetralins 6 and 1-arylnaphthalenes 8 via (1) K2CO3-mediated α-styrylation of β-ketosulfones 3 with bromostyryl bromides 4 and (2) stereocontrolled NaBH4-promoted reduction of the resulting γ-alkenones 5, followed by BF3·OEt2-catalyzed intramolecular annulation of the corresponding γ-alkenols 7 under rt/5 h and reflux/10 h conditions, respectively. The key structures of 6 and 8 were confirmed by X-ray crystallographic analysis. A plausible mechanism has been proposed.",10.1021/acs.orglett.6b00603,2016-03-15,0.57788061584898
Angewandte Chemie International Edition,Enantioselective Synthesis of Arglabin,"Closing the ring: The first enantioselective synthesis of the guanianolide natural product arglabin and its dimethylamino adduct, which shows promising results in the treatment of various tumors, has been achieved. Key steps include a CuI-catalyzed asymmetric cyclopropanation, a stereoselective Sakurai allylation with a retroaldol/lactonization cascade, and a second Sakurai allylation with ring-closing metathesis (RCM).",10.1002/anie.200701584,2007-07-16,0.5778778583043849
Journal of Organic Chemistry,Aromatics to Triquinanes:  <i>p</i>-Cresol to (±)-Δ<sup>9(12)</sup>-Capnellene,"A novel, efficient and stereospecific synthesis of the marine natural product capnellene from p -cresol is described. Generation of 4-methyl-6,6-spiroepoxycyclohexa-2,4-dienone ( 9 ) from 5-methylsalicyl alcohol ( 8 ), its in situ cycloaddition with cyclopentadiene (in situ), and the photochemical oxa-di-π-methane reaction of an endo tricyclo[5.2.2.0 2,6 ]undecenone are the key features of our strategy. An efficient synthetic route to appropriately designed endo tricyclo[5.2.2.0 2,6 ]undecenones (compounds 6, 11−13 ) endowed with most of the structural and stereochemical features of capnellene, from the keto epoxide 7, are described. The photochemical reaction of 6, and 11b,d upon sensitized irradiation readily gave the oxa-di-π-methane products 5, 14, and 15 respectively. The tetracyclic compound 5 was elaborated to capnellene after cleavage of the peripheral cyclopropane bond, Barton's deoxygenation, deprotection of the carbonyl group, and Wittig reaction.",10.1021/jo980064g,1998-05-20,0.5778749807025787
Journal of Organic Chemistry,"Unified Total Syntheses of Fawcettimine Class Alkaloids: Fawcettimine, Fawcettidine, Lycoflexine, and Lycoposerramine B","The total syntheses of the lycopodium alkaloids fawcettimine, fawcettidine, lycoflexine, and lycoposerramine B have been accomplished through an efficient, unified, and stereocontrolled strategy that relies on a Diels-Alder reaction to construct the cis-fused 6,5-carbocycles with one all-carbon quaternary center. Access to the enantioselective syntheses of both antipodes of those alkaloids can be achieved by kinetic resolution of the earliest intermediate via a Sharpless asymmetric dihydroxylation (Sharpless AD). Compared to existing approaches to these alkaloids, our synthetic route possesses superior stereocontrol over the C-4 and C-15 stereogenic centers as well as allowing for more functional variation on the 6-membered ring.",10.1021/jo3006045,2012-04-21,0.577855776038486
European Journal of Organic Chemistry,Indole–Indole Ullmann Cross‐Coupling for C<sub>Ar</sub>–N Bond Formation: Total Synthesis of (–)‐Aspergilazine A,"The copper‐catalyzed cross‐coupling reaction of indole and protected haloindoles (X = Br, I) by using CuI, N , N′ ‐dimethylethylenediamine, and K 2 CO 3 in dioxane at 130 °C afforded the corresponding bis‐indole products in generally high yields. Starting from the N1′–C6 bis‐indole positional isomer obtained by C Ar –N Ullmann coupling, a new synthesis of (–)‐aspergilazine A was completed. A bidirectional Negishi‐catalyzed cross‐coupling of the C3,C3′‐diiodo N1′–C6 bis‐indole derivative was used to construct the corresponding bis‐tryptophan. Amide formation with l ‐proline and thermally induced deprotection/cyclization completed the diketopiperazine units of (–)‐aspergilazine A.",10.1002/ejoc.201700842,2017-06-30,0.5778500185991499
Tetrahedron,"A practical and efficient synthesis of 6-carboalkoxy-13-cycloalkyl-5H-indolo[2,1-a][2]benzazepine-10-carboxylic acid derivatives",,10.1016/j.tetlet.2013.12.085,2014-01-03,0.5778465753215296
Organic Process Research & Development,"The Chemical Development of CI-972 and CI-1000:  A Continuous Nitration, A MgCl<sub>2</sub>/Et<sub>3</sub>N-Mediated C-Alkylation of a Chloronitropyrimidine, A Catalytic Protodediazotization of a Diazonium Salt, and an Air Oxidation of an Amine","Efficient, large-scale processes were developed for the preparation of the potent PNP inhibitors 2,6-diamino-3,5-dihydro-7-(3-thienylmethyl)-4 H -pyrrolo[3,2- d ]pyrimidin-4-one hydrochloride, monohydrate ( 1 ) and 2-amino-3,5-dihydro-7-(3-thienylmeth-yl)-4 H -pyrrolo[3,2- d ]pyrimidin-4-one hydrochloride, monohydrate ( 2 ). We report (1) a safe, continuous nitration process for the preparation of 2-amino-6-chloro-5-nitro-4-pyrimidinol ( 8a ) and its stable diisopropylamine salt ( 8b ), (2) the first MgCl 2 /Et 3 N-mediated C-alkylation of a chloronitropyrimidine, (3) a rare catalytic protodediazotization of the diazonium salt 2-amino-4-oxo-7-thiophen-3-ylmethyl-4,5-dihydro-3H-pyrrolo[3,2- d ]pyrimidine-6-diazonium chloride ( 14 ), (4) a single-step process to prepare 2 directly from 2-amino-6-hydroxy-5-nitro-α-(3-thienylmethyl)-4-pyrimidineacetonitrile ( 12 ) using a sponge nickel-catalyzed reduction, and (5) a method to convert the over-reduction by-product 2,5-diamino-6-(1-aminomethyl-2-thiophen-3-yl-ethyl)-pyrimidin-4-ol ( 16 ) into 2 using air oxidation.",10.1021/op000298d,2001-04-20,0.5778426579660711
Tetrahedron,Studies on the total synthesis of rifamycin. Highly stereoselective synthesis of intermediates for construction of the C(15) to C(29) chain,,10.1016/s0040-4039(01)85964-5,1979-01-01,0.5778417768975875
Angewandte Chemie International Edition,The Interleukin-4-Receptor: From Recognition Mechanism to Pharmacological Target Structure,"Organic synthesis of hormone derivatives is an established route to yield pharmacologically active agents. Until recently this has only been feasible for small organic compounds, but nowadays it is also possible to produce antagonists for larger protein hormones. In particular, the interleukin-4-receptor was a well-suited target for this approach since it plays a pivotal role in the release and progression of allergic diseases. Accordingly, a strong interest and a high medical need is associated with the development of inhibitors. The structural elucidation of the ligand/receptor complex and an improved understanding of the mechanisms concerning receptor binding and activation allow for the rational design of variants that inhibit interleukin-4. Since it is possible to specifically inhibit the interleukin-4-receptor system in this way, a completely new approach to the development of new drugs against allergy and asthma has been established.",10.1002/1521-3773(20000818)39:16<2834::aid-anie2834>3.0.co;2-k,2000-08-18,0.5778415246957119
Tetrahedron,Diastereoselective synthesis of a core fragment of ritonavir and lopinavir,,10.1016/j.tetlet.2011.10.087,2011-10-24,0.5778395100137607
European Journal of Organic Chemistry,A Unified Strategy for Kainoid Synthesis,"Abstract A unified strategy for kainoid synthesis was developed. The key features of the strategy involve a Claisen–Ireland rearrangement to construct the contiguous stereogenic centers and a palladium‐catalyzed formation of the pyrrolidine ring with complete stereoselectivity. The present protocol has enabled rapid access to a wide range of kainoids with diverse types of substituents (alkenyl, aryl, and alkyl groups) at the 4‐position of the pyrrolidine ring, starting from the common intermediate and appropriate acetic acid derivatives. To test the generality of the strategy, we have accomplished the syntheses of kainic acid, o ‐methoxyphenyl derivative (MFPA), and a novel cyclopropyl derivative (CPKA), using 3‐methylbut‐3‐enoic acid, 2‐(2‐methoxyphenyl)acetic acid, and 2‐cyclopropylacetic acid, respectively.",10.1002/ejoc.201402452,2014-06-23,0.5778384605559265
Journal of the American Chemical Society,"Unified Strategy to Monoterpene Indole Alkaloids: Total Syntheses of (±)-Goniomitine, (±)-1,2-Dehydroaspidospermidine, (±)-Aspidospermidine, (±)-Vincadifformine, and (±)-Kopsihainanine A","Total syntheses of (±)-goniomitine, (±)-1,2-dehydroaspidospermidine, (±)-aspidospermidine, (±)-vincadifformine, and (±)-kopsihainanine A were achieved featuring two common key steps: (1) a palladium-catalyzed decarboxylative vinylation that provides quick access to cyclopentene intermediates containing all of the carbons present in the natural products and (2) an integrated oxidation/reduction/cyclization (iORC) sequence for skeletal reorganization that converts the cyclopentenes to the pentacyclic structures of the natural products. By incorporation of a geometric constraint to iORC substrates, both the chemoselectivity (C7 vs N1 cyclization) and the stereoselectivity (trans- vs cis-fused ring system) of the cyclization process can be controlled.",10.1021/ja509329x,2014-10-01,0.5778383004285057
Organic Letters,Highly Efficient Synthesis of DNA-Binding Polyamides Using a Convergent Fragment-Based Approach,"Two advances in the synthesis of hairpin pyrrole-imidazole polyamides (PAs) are described. First, the application of a convergent synthetic strategy is shown, involving the Boc-based solid phase synthesis of a C-terminal fragment and the solution phase synthesis of the N-terminal fragment. Second a new hybrid resin is developed that allows for the preparation of hairpin PAs lacking a C-terminal β-alanine tail. Both methods are compatible with a range of coupling reagents and provide a facile, modular route to prepare PA libraries in high yield and crude purity.",10.1021/ol502203y,2014-08-27,0.577836278190641
Tetrahedron,Efficient synthesis of neomycin B related aminoglycosides,,10.1016/s0040-4039(00)00586-4,2000-05-01,0.5778360360421421
Tetrahedron,"One-pot synthesis of novel 1,2,6,7-tetrahydro-3H-pyrazolo[4,3-c]pyridine-3,4(5H)-diones",,10.1016/j.tetlet.2018.08.036,2018-08-22,0.5778306724472959
Synthesis,"An Efficient Synthesis of Dibenzocycloocta-4a,6a,-diene-5,11-diyne and its Precursors","Two efficient syntheses of dibenzocyclooctadienediyne 1 were developed employing known reactions, which utilize commercially available reagents. Both methods are an improvement on known syntheses resulting in 41% and 43% overall yields. The latter method also offers an efficient synthesis of dibenzocyclooctatetraene 9, which is one of the key reagents now commercially unavailable.",10.1055/s-2002-32542,2002-06-28,0.5778286967845794
European Journal of Organic Chemistry,"Stereocontrolled Synthesis of Highly Substituted <i>trans</i> α,β‐Unsaturated Ketones with Potent Anticancer Properties from Glycals","A novel synthetic route for highly substituted conjugated ketones has been developed utilizing glycals as starting materials. The two‐step process combined the Heck reaction/Lewis acid promoted ring opening to afford the products in 33–80 % overall yields and with a high level of trans stereoselectivity. Since the products are essentially the aldols, this methodology may be employed in some cases as an alternative synthetic route to the typical aldol condensation. Densely substituted, selectively protected conjugated ketones are synthetically attractive structures which, in our case, proved to be biologically equally appealing. Namely, they showed activity against several cancer cell lines, such as HeLa, K562, MDA‐MB‐453, in some instances overperforming cisplatin used as a standard.",10.1002/ejoc.201900672,2019-06-24,0.5778187777841441
Tetrahedron,Synthetic approach to grayanotoxins: a new method for the construction of the a-homograyanotoxane ring system,,10.1016/s0040-4039(01)82912-9,1981-01-01,0.5778142307314204
Angewandte Chemie International Edition,Total Synthesis of (±)‐Cristaxenicin A: Construction of Nine‐Membered Ring by Eschenmoser–Claisen/Cope Rearrangement Cascade,"Cristaxenicin A, a natural marine product with a skeleton consisting of a nine-membered carbocycle fused with a dihydropyran ring, displays strong antiprotozoal activity against Leishmania amazonensis and Trypanosoma congolense. The synthesis of cristaxenicin A is challenging because of its unique oxidation pattern at C11 and C20, the cis-cyclononane with a C5─C6 double bond, and the C1─C19 alkene moiety functionalized as an enol acetate. Herein, we report the first total synthesis of (±)-cristaxenicin A. The nine-membered ring was constructed from 2,2-divinylcyclopentanecarbonitrile through an addition reaction with 4-(tert-butyldimethylsilyl)oxy-2-butenal followed by a one-pot sequence of the Eschenmoser-Claisen and Cope rearrangement reactions. After the formation of a trans-fused bicyclo[7.3.0]dodecane skeleton through an intramolecular Stetter reaction, the cyclopentane ring was transformed into a dihydropyran ring by oxidative cleavage, followed by intramolecular acetalization. Two reactions described herein, namely, the formation of a cyclononadiene ring via the Cope rearrangement without using an oxy-Cope substrate and a new protocol for the construction of a dihydropyran ring from a cyclopentene derivative, provide a powerful tool for the total synthesis of natural products with highly functionalized complex structures.",10.1002/anie.202524855,2025-12-28,0.5778126278336972
Green Chemistry,Metal-free tandem cyclization/hydrosilylation to construct tetrahydroquinoxalines,"B(C <sub>6</sub> F <sub>5</sub> ) <sub>3</sub> -Catalyzed tandem cyclization/hydrosilylation for the step-economical construction of 1,2,3,4-tetrahydroquinoxalines from readily available starting materials has been developed.",10.1039/c7gc03095a,2017-11-03,0.5778106088199699
Synthesis,Stereoselective Synthesis of Piperidines,"All articles of this category This review presents the recent progress in the stereoselective formation of piperidines focussing on synthetic key steps. Both chiral pool-derived routes, auxiliary controlled methods and catalytic asymmetric reactions are described. piperidines - stereoselective synthesis - chiral auxiliaries",10.1055/s-2000-8218,2000-01-01,0.5778099428393011
Tetrahedron,Organocatalytic enantioselective conjugate addition of 2-nitrocyclohexanone to acrylaldehyde: a concise two-step synthesis of chiral building block 1-azaspiro[4.5]decan-6-one,,10.1016/j.tetlet.2013.01.114,2013-02-05,0.5778079139723108
Organic Letters,Total Synthesis of <i>e</i><i>pi</i>-7-Deoxypancratistatin via Aza-Payne Rearrangement and Intramolecular Cyclization,"[reaction: see text] epi-7-Deoxypancratistatin containing the cis-fused phenanthridone core was synthesized in 12 steps from bromobenzene. Key features of this synthesis include the enzymatic oxidation of bromobenzene with toluene dioxygenase, selective opening of a cyclic sulfate over an aziridine with oxygen nucleophiles, and an intramolecular Lewis acid-catalyzed cyclization onto an epoxy conduramine derived via aza-Payne rearrangement.",10.1021/ol0169877,2001-12-11,0.5778070875972708
Synthesis,"A Novel Route to Methyl 3-(3,4-Disubstituted 5-alkylthio/amino-2-thienyl) propenoates","All articles of this category The 3-oxodithioesters 1 and 3-oxothioamides 6 are shown to undergo base catalyzed S -alkylation with methyl 4-bromocrotonate followed by intramolecular condensation to give the corresponding methyl 3-(3,4-disubstituted 5-alkylthio/amino-2-thienyl) propenoates 5 and 7 in good yields.",10.1055/s-1988-27638,1988-01-01,0.5777994033419722
Organic Letters,Alkyl C−O Ring Cleavage of Bicyclic β-Lactones with Normant Reagents:  Synthesis of a Merck IND Intermediate,"Highly diastereoselective Cu(I)-mediated, bicyclic beta-lactone ring cleavage reactions with either alkyl or aryl cuprates proceeded with inversion of stereochemistry to give optically active trans-substituted cyclopentanes and cyclohexanes. Optimization of typically problematic aryl cuprate additions was made possible by minimization of a competing bromide-induced ring cleavage process. The utility of this process was demonstrated by an efficient synthesis of a Merck investigational new drug (IND) intermediate for an anti-HIV CCR5 antagonist.",10.1021/ol070572p,2007-05-01,0.577795883054749
Tetrahedron,"A new route to selectively protected cis 4a-methyl-hexahydronaphthalene-1(2H), 7(8H)-diones",,10.1016/s0040-4039(00)84544-x,1986-01-01,0.5777923764500278
Tetrahedron,"A simple and efficient total synthesis of (±)-danshexinkun A, a bioactive diterpenoid from Salvia miltiorrhiza",,10.1016/j.tetlet.2009.11.093,2009-11-28,0.5777862693249083
Tetrahedron,"(R)-6,6′-Bis(trifluoromethanesulfonyl)-2,2′-dihydroxy-1,1′-binaphthyl: a new ligand for asymmetric synthesis",,10.1016/j.tetlet.2006.04.069,2006-05-11,0.5777736295013371
Journal of Organic Chemistry,Enantioselective Synthesis of Fused Isocoumarins via Palladium-Catalyzed Annulation of Alkyne-Tethered Malononitriles,"An enantioselective palladium-catalyzed annulation of alkyne-tethered malononitriles for the synthesis of 3,4-ring-fused isocoumarins is described. This cascade strategy involves oxypalladation of ortho -alkynylbenzoates and desymmetrizing addition onto one cyano group of the pendant malononitriles, which enables the concurrent construction of two rings and an all-carbon quaternary stereocenter in a single operation.",10.1021/acs.joc.1c01026,2021-07-13,0.5777691489065581
Journal of Organic Chemistry,Biomimetic Total Synthesis of (±)-8-Oxoerymelanthine,"Erymelanthine 1 and 8-oxoerymelanthine 2 are unique erythrina alkaloids containing a pyridine ring. We synthesized (+/-)-8-oxoerymelanthine 2 in 2.0% overall yield using the following key reactions. The characteristic 6-5-6-6-membered ring system was constructed by the stereoselective intermolecular Diels-Alder reaction. Oxidative cleavage of the aromatic D-ring was conducted chemo- and regioselectively by ozonolysis in the presence of BF(3)-etherate. This cleavage site is identical to the site cleaved during the biosynthesis of erymelanthine 1. Nitrogen incorporation was achieved by aminolysis. Conversion of the D-ring pyridone to the corresponding pyridine was efficiently accomplished by palladium-catalyzed reduction of aryl triflate 21. This is not only the first total synthesis of (+/-)-8-oxoerymelanthine 2 (where the D-ring is pyridine) but also, more importantly, a biomimetic total synthesis of an erythrinan D-aza alkaloid.",10.1021/jo9008645,2009-07-08,0.5777683143546403
Journal of Organic Chemistry,Process for (<i>S</i>)-Ketamine and (<i>S</i>)-Norketamine via Resolution Combined with Racemization,"A concise, recyclable, and efficient process is presented for the preparation of ( S )-ketamine (esketamine, ( S )- 1a ) via classic resolution combined with the recycling of the undesired isomer. With commercially available ketone 2 as the starting material, this procedure features three steps including (1) an unique hydroxylation-ring expansion rearrangement, (2) mild amination via methanesulfonate, and (3) chiral separation using L -(+)-tartaric acid. The three simple steps are all performed in mild conditions and ( S )- 1a tartrate is obtained in 99.5% ee without recrystallization. Subsequently, racemization of the unwanted ( R )- 1a remained in resolution mother liquor was performed in the presence of a Lewis acid in quantitative yield with >99.0% chemical purity. This original and economical process afforded esketamine in 67.4% (28.9% without racemization) overall yield with two times recycling of the mother liquor without column purification. In addition, this procedure can also be applied to the preparation of ( S )-norketamine, which is a safer potential antidepressant.",10.1021/acs.joc.0c01090,2020-06-08,0.5777618212310257
Tetrahedron,Diastereoselective hydroformylation of acyclic olefins: Efficient construction of an all-anti stereotriade building block for polyketide synthesis,,10.1016/s0040-4039(98)00158-0,1998-04-01,0.5777596869629322
Tetrahedron,"One-pot synthesis of a natural product inspired pyrrolocoumarine compound collection by means of an intramolecular 1,3-dipolar cycloaddition as key step",,10.1016/j.tetlet.2015.01.021,2015-01-09,0.5777549088252103
Tetrahedron,Regiospecific synthesis of 11-desoxyanthracycline antibiotics starting with aloe-emodin,,10.1016/s0040-4039(01)82000-1,1981-01-01,0.5777542113446343
Organic Letters,Diastereoselective Intramolecular Friedel–Crafts Alkylation of Tetralins,"An efficient and versatile synthesis of cis-hexahydrobenzophenanthridines starting from readily available tetralins has been developed using an intramolecular Friedel-Crafts alkylation as a key step. The substrates were prepared via a highly stereocontrolled rhodium-catalyzed ring-opening reaction of meso-oxabicyclic alkenes and a hydrogenation sequence. Thus, a wide variety of complex tetracyclic compounds have been isolated with a high level of regio-, diastereo-, and enantioselectivity.",10.1021/ol2008236,2011-05-18,0.5777540515901072
Synlett,Enantioselective Synthesis of Reported Hippospongic Acid A,"All articles of this category Total synthesis of hippospongic acid A, an inhibitor of gastrulation of starfish embryos, has been studied. A compound having the structure assigned to hippospongic acid A was synthesized enantioselectively. The spectral data of the synthetic compound were slightly different from those of the natural product and an alternative structure was proposed for the natural product. hippospongic acid A - enantioselective synthesis - baker's yeast reduction - revised structure proposal",10.1055/s-1998-1781,1998-07-01,0.5777505319493305
Journal of Organic Chemistry,Synthesis of a precursor to quassimarin,An intermediate containing the ACE ring system of quassimarin was prepared. The isopropylidene malonate 8 reacted with diene 2 to afford two Diels-Alder adducts. The major adduct was converted into lactone 11 by a sequence involving epoxidation followed by acid-mediated epoxide opening and lactonization.,10.1021/jo00367a017,1986-08-01,0.5777502795624581
Organic Letters,Synthesis and Properties of Ethene-Bridged Terthiophenes,"A method for the facile synthesis of ethene-bridged terthiophenes (EBTTs) in two steps has been developed. The first step is a double Sonogashira coupling between 3',4'-dibromo-2,2':5',2″-terthiophene and terminal alkynes to give dialkynylated terthiophenes, and the second step is a cyclization reaction to afford EBTTs. The fundamental physical properties of EBTTs were also studied.",10.1021/acs.orglett.5b02417,2015-09-18,0.5777494828312614
Synlett,"7a-Hydroxy-1,4,5,6,7,7a-hexahydro-2<i>H</i>-inden-2-ones by Ring Enlargement and Subsequent Photooxygenation of 1,2-Dihydropentalenes","All articles of this category 1,2-Dihydropentalenes are converted into the title compounds by a four-step synthesis involving highly diastereoselective cyclopropanation and singlet oxygen photooxygenation steps.",10.1055/s-1993-22493,1993-01-01,0.5777456049778695
Tetrahedron,A novel synthesis of 1-aryl-3-piperidone derivatives,,10.1016/j.tetlet.2012.11.085,2012-11-29,0.5777393263538024
Tetrahedron,A convenient intermediate for 4-demethoxyanthracyclinone synthesis,,10.1016/s0040-4039(00)81913-9,1983-01-01,0.5777304512908322
Organic Letters,"Diastereoselective Synthesis of CF<sub>3</sub>-Substituted Spiroisochromans by [1,5]-Hydride Shift/Cyclization/Intramolecular Friedel–Crafts Reaction Sequence","Developed herein is a diastereoselective synthesis of CF 3 -substituted spiroisochromans via C(sp 3 )–H bond functionalization involving sequential transformations ([1,5]-hydride shift/cyclization/elimination of MeOH/intramolecular Friedel–Crafts reaction).",10.1021/acs.orglett.9b00668,2019-03-18,0.5777284604768036
Synthesis,"Controllable Monoaddition of Carbon Nucleophiles to 1,2,3,4-Diepoxybutane: Two-directional Chain Extension of a C<sub>2</sub> Symmetric Four Carbon Diepoxide as a Route to Differentiated <i>Syn</i> 1,2-Diols","A strategy for the construction of unsymmetrically protected isolated syn 1,2-diols bearing various unsaturated appendages is described. Reaction conditions are described for selective monoaddition to C2 symmetric 1,2,3,4-diepoxybutane which permits both differential protection of the intermediate epoxy alcohols and a second chain elongation. This sequence provides access to unsymmetrical mono-protected diols bearing unsaturated appendages not readily accessible by asymmetric dihydroxylation.",10.1055/s-2002-34391,2002-09-26,0.5777271480201676
Synthesis,From Paracetamol to Rolipram and Derivatives: Application of Deacetylation-Diazotation Sequences and Palladium-Catalyzed Matsuda-Heck Reaction,"A six-step synthesis of the antidepressant rolipram from the popular analgetic 4-acetamidophenol (paracetamol) is described. The steps include oxidative functionalization of the aromatic core, diazonium salt formation via deacetylation-diazotation, Matsuda–Heck reaction, conjugate addition of nitromethane, and hydrogenative cyclization.",10.1055/s-0032-1316874,2013-03-14,0.5777257110255428
Tetrahedron,"A facile route for the synthesis of novel S-linked 1,3,5-triazine tethered peptidomimetics",,10.1016/j.tetlet.2014.08.075,2014-08-23,0.5777231683965435
Synlett,"New Efficient Synthesis ofPyrido[2,3-<i>c</i>] and Pyrido[3,2-<i>c</i>]coumarin Derivatives","Various substituted pyrido[2,3-c] and pyrido[3,2-c]coumarins are efficiently prepared in three steps from 3- and 4-hy­droxycoumarins, respectively and protected β-aminoketones.",10.1055/s-2003-39302,2003-01-01,0.5777177192345067
Angewandte Chemie International Edition,Highly Enantioselective Tandem Michael Addition of Tryptamine‐Derived Oxindoles to Alkynones: Concise Synthesis of Strychnos Alkaloids,"Abstract A highly enantioselective tandem Michael addition of tryptamine‐derived oxindoles to alkynones was developed by taking advantage of a chiral N , N′ ‐dioxide Sc(OTf) 3 catalyst. The reaction enables the facile preparation of enantioenriched spiro[pyrrolidine‐3,3′‐oxindole] compounds, which provides a novel strategy for the synthesis of monoterpenoid indole alkaloids. As a demonstration, the asymmetric synthesis of strychnos alkaloids [(−)‐tubifoline, (−)‐tubifolidine, (−)‐dehydrotubifoline] was achieved in 10–11 steps.",10.1002/anie.201800567,2018-02-08,0.5777023938039848
Journal of Organic Chemistry,"Syntheses of Strychnan- and Aspidospermatan-Type Alkaloids. 9.<sup>1</sup> The Enantioselective Generation of Tetracyclic ABCE Intermediates by a Tandem Condensation, [3,3]-Sigmatropic Rearrangement, and Cyclization Sequence","Reactions of substituted acroleins with the tryptophan-derived benzyl 2-(benzylamino)-3-[3-[2-[(methoxycarbonyl)methyl]indolyl]]propionate gave tetracyclic hexahydro-1H-pyrrolo[2,3-d] intermediates with stereoselective placement of substituents for cyclization to pentacyclic Strychnos alkaloids. The benzyl ester moiety was readily removed by formation of a corresponding nitrile and reduction, thus providing enantioselective syntheses of the tetracyclic compounds.",10.1021/jo970207j,1997-11-01,0.5777012109570137
Synlett,"Stereoselective Synthesis of 1,2,2-Trisubstituted Indane Derivatives Using a Tandem S<sub>N</sub>2-Michael Addition Sequence","An efficient strategy is developed for the synthesis of 1,2,2-trisubstituted indane derivatives employing a tandem SN2-Michael reaction sequence. The method is extended towards the synthesis of spiroindanes and indanopiperidines.",10.1055/s-2007-984526,2007-07-01,0.5776932088324129
Tetrahedron,Diversity oriented synthesis: concise entry to novel derivatives of Yohimbine and Corynanthe alkaloids,,10.1016/j.tetlet.2011.10.115,2011-11-01,0.5776887768800698
Tetrahedron,Asymmetric synthesis via heteroconjugate addition: valinol template as oxazolidine heteroolefin vs acetylenic nucleophiles,,10.1016/s0040-4039(00)97882-1,1990-01-01,0.5776877885656774
Tetrahedron,A convenient two-step one-pot synthesis of phosphonamidates,,10.1016/s0040-4039(97)10421-x,1997-12-01,0.5776757409371992
Tetrahedron,"Practical, asymmetric synthesis of aromatic-substituted bulky and hydrophobic tryptophan derivatives",,10.1016/s0040-4039(01)01626-4,2001-10-01,0.5776732233547544
Tetrahedron,"Pd-mediated synthesis of novel pentacyclic benzoazepino[2,1-a]isoindoles from enamides of Baylis–Hillman adducts",,10.1016/j.tetlet.2007.10.043,2007-10-30,0.57767055466332
Tetrahedron,Asymmetric synthesis XIII synthesis of 2-alkylpyrrolidines: Towards azabicyclic systems,,10.1016/s0040-4039(00)80168-9,1988-01-01,0.5776704911380783
Tetrahedron,"Synthesis of a protein biosynthesis inhibitor, 5′-tri-phosphoryladenylyl-(2′-5′)-adenosine",,10.1016/s0040-4039(01)95495-4,1979-01-01,0.5776664602855611
Synlett,A Short Preparation of an AdvancedIntermediate for Lactacystin Synthesis: The Complete Carbon Skeletonof Clasto-Lactacystin Dihydroxyacid,"An advanced intermediate 22 for lactacystin Synthesis, containing the full carbon skeleton of the pyrrolidinone component, has been achieved in four steps from a protected glycine ester.",10.1055/s-2003-39290,2003-01-01,0.5776659409948104
Tetrahedron,trans-4-Hydroxy-l-proline: a novel starting material for N-alkylpyrroles synthesis,,10.1016/j.tetlet.2011.04.045,2011-04-21,0.5776613612089855
Organic Process Research & Development,Development of a Hydrogenative Reductive Amination for the Synthesis of Evacetrapib: Unexpected Benefits of Water,"For the synthesis of cholesteryl ester transfer protein (CETP) inhibitor evacetrapib, a hydrogenative reductive amination was chosen to join the substituted cyclohexyl subunit to the benzazepine core. The addition of water, which suppressed undesired epimerization without affecting the rate of product formation, was key to the reaction’s success. The process was scaled to produce more than 1100 kg of material.",10.1021/op500025v,2014-03-18,0.5776604735489141
Journal of the American Chemical Society,Total Synthesis of (−)-Chromodorolide B By a Computationally-Guided Radical Addition/Cyclization/Fragmentation Cascade,"The first total synthesis of a chromodorolide marine diterpenoid is described. The core of the diterpenoid is constructed by a bimolecular radical addition/cyclization/fragmentation cascade that unites two complex fragments and forms two C-C bonds and four contiguous stereogenic centers of (-)-chromodorolide B in a single step. This coupling step is initiated by visible-light photocatalytic fragmentation of a redox-active ester, which can be accomplished in the presence of an iridium or a less-precious electron-rich dicyanobenzene photocatalyst, and employs equimolar amounts of the two addends. Computational studies guided the development of this central step of the synthesis and provide insight into the origin of the observed stereoselectivity.",10.1021/jacs.7b13799,2018-02-07,0.5776604021127058
Journal of the American Chemical Society,Trapping of a Borirane Intermediate in the Reductive Coupling of an Arylborane to a Diborene,"The reductive coupling of a N-heterocyclic carbene (NHC)-stabilized aryldibromoborane yields a mixture of trans - and cis -diborenes in which the aryl groups are coplanar with the diborene core. Under dilute reduction conditions two diastereomers of a borirane–borane intermediate are isolated, which upon further reduction give rise to the aforementioned diborene mixture. DFT calculations suggest a mechanism proceeding via nucleophilic attack of a dicoordinate borylene intermediate on the aryl ring and subsequent intramolecular B–B bond formation.",10.1021/jacs.0c02306,2020-03-09,0.5776600953718061
Tetrahedron,Formal total synthesis of borrelidin: synthesis of C1–C11 fragment via desymmetrization strategy,,10.1016/j.tetlet.2009.03.196,2009-04-03,0.5776588104877367
Tetrahedron,Synthesis of an epoxyquinol analog: efficient methodology for the insertion of side chains into cyclohexenone cores,,10.1016/j.tetlet.2010.10.138,2010-11-01,0.5776562630690724
Synthesis,"Synthesis of the Trifluoroacetate Salt of Aspartic Acid β-Semialdehyde, an Intermediate in the Biosynthesis of L-Lysine, L-Threonine, and L-Methionine","All articles of this category The trifluoroacetate salt of aspartic acid ß-semialdehyde, an important intermediate in the biosynthesis of L-lysine, L-threonine, and L-methionine has been prepared in DL-, L-, and D-forms as stable solid hydrates 13 in 43% overall yield by ozonolysis of doubly protected allylglycine, followed by careful deprotection with trifluoroacetic acid.",10.1055/s-1993-25994,1993-01-01,0.5776549001760105
Tetrahedron,An efficient synthesis of furano analogs of duocarmycin C1 and C2: seco-iso-cyclopropylfurano[e]indoline-trimethoxyindole and seco-cyclopropylfurano[f]quinoline-trimethoxyindole,,10.1016/j.tetlet.2014.04.062,2014-04-26,0.5776496622794852
Tetrahedron,"Synthesis of (8Z,14Z)-13,13-dimethyleicosa-8,14-dien-11-ynoic acid as an inhibitor of prostaglandin cyclooxygenase",,10.1016/s0040-4039(01)83479-1,1977-01-01,0.5776446388227855
Tetrahedron,"An efficient route to 3-deoxy-d-manno-2-octulosonic acid (KDO) derivatives via a 1,4-cyclic sulfate approach",,10.1016/s0040-4039(01)80598-0,1989-01-01,0.5776440834111909
Tetrahedron,Studies on the total synthesis of sanglifehrin A: stereoselective synthesis of the C(29)–C(39) fragment,,10.1016/j.tetlet.2006.01.105,2006-02-08,0.5776285033055115
Organic Letters,A Bioinspired Strategy for the Enantioselective Synthesis of Bicyclic Oxygen Heterocycles,"A new strategy is described for the direct conversion of unsaturated 3,5-dihydroxy-diarylheptanoids to dimeric products assembled on trans -2,8-dioxabicyclo[4.4.0]decane frameworks. The key atom-economical acid-mediated coupling creates 2 rings and 4 new stereocenters in a single-pot process. Oxygen-18 labeling studies are in accord with reactions proceeding via a cascade mechanism involving carbocationic intermediates. This approach enabled the concise total syntheses of analogues of the natural product blepharocalyxin D in 4 steps from simple starting materials.",10.1021/acs.orglett.0c00425,2020-03-16,0.5776177481777859
Tetrahedron,Design and synthesis of indole derivatives of adenophostin A. A entry into subtype-selective IP3 receptor ligands,,10.1016/j.tetlet.2009.12.045,2009-12-17,0.5776154962460933
Tetrahedron,Towards a total synthesis of (−)-cephalotaxine: construction of the BCDE-tetracyclic core,,10.1016/s0040-4039(02)01219-4,2002-08-01,0.5776121740597597
Tetrahedron,First synthesis of (+)-deoxoartemisitene and its novel C-11 derivatives,,10.1016/s0040-4039(01)00641-4,2001-06-01,0.5776104258611379
Tetrahedron,"Highly efficient synthesis of 5,6-disubstituted-5H-pyrrolo[2,3-b]pyrazine-2,3-dicarbonitriles through a one-pot palladium-catalyzed coupling reaction/cyclization in water",,10.1016/j.tetlet.2012.04.016,2012-04-12,0.5776103482073482
Organic Process Research & Development,"The Synthesis of OSU 6162:  Efficient, Large-Scale Implementation of a Suzuki Coupling","The synthesis of the chiral, nonracemic 3-aryl piperidine, OSU 6162 ( 1 ), a potential CNS agent from Pharmacia Corporation, is presented. The key construction in the described synthesis is a palladium-catalyzed aryl cross-coupling reaction between bromosulfone ( 4 ) and pyridyl borane ( 14 ). Initially developed conditions for this Suzuki reaction, conducted in tetrahydrofuran/aqueous hydroxide, delivered free base ( 6 ) or hydrochloride salt ( 15a ) in reproducible 80% yield. However, by changing the solvent to toluene and the base to carbonate, significant decreases in catalyst requirement were realized, and the methane sulfonate salt ( 15b ) of the coupled product could be obtained in reproducible 92−94% yield on 200-kg input. The success of the Suzuki reaction was critically dependent on a bulk source of the pyridyl borane coupling partner. Cryogenic conditions were developed for its generation via lithium−halogen exchange to generate thermally labile 3-lithiopyridine followed by transmetalation with diethylmethoxy borane. This highly exothermic series of transformations yielded crystalline diethyl-3-pyridyl borane in reproducible 75−80% yield on scales ranging up to 200-kg input. Selective reduction of the biaryl, classical resolution and introduction of the propyl group via the Gribble reductive amination procedure completed the synthesis of OSU 6162 free base. This route was employed to deliver over 35 kg of clinical-quality bulk drug in short order.",10.1021/op025620u,2003-02-08,0.5776053441537934
Angewandte Chemie International Edition,Protecting‐Group‐Free Total Synthesis of (−)‐Rhazinilam and (−)‐Rhazinicine using a Gold‐Catalyzed Cascade Cyclization,‘Rhaz'zmatazz: A total synthesis of (−)-rhazinilam and the first asymmetric total synthesis of (−)-rhazinicine were accomplished by using constructing the indolizinone core through the gold-catalyzed cyclization of a fully elaborated linear ynamide. The scope and generality of this cascade reaction for the construction of highly substituted indolizinones were also investigated.,10.1002/anie.201303067,2013-06-06,0.5776018085639028
Synthesis,Diversity-Oriented Stereocontrolled Synthesis of Some Piperidine- and Azepane-Based Fluorine-Containing β-Amino Acid Derivatives,"Abstract Structural diversity-oriented synthesis of some azaheterocyclic β-amino acid derivatives has been accomplished by selective functionalization of readily available cyclodienes. The stereocontrolled synthetic concept was based on the oxidative ring cleavage of unsaturated cyclic β-amino acids derived from cycloalkadiene, followed by ring closing with double reductive amination, which furnished some conformationally restricted β-amino acid derivatives with a piperidine or azepane core.",10.1055/s-0040-1706637,2020-12-14,0.5776006765933901
Angewandte Chemie International Edition,"Synthesis of Atisine, Ajaconine, Denudatine, and Hetidine Diterpenoid Alkaloids by a Bioinspired Approach","A unified approach to four different (atisine, ajaconine, denudatine, and hetidine) diterpenoid alkaloid skeletons was developed and applied to the total synthesis of the natural products dihydroajaconine (2, atisine type) and gymnandine (4, denudatine type). The synthesis features a biogenetically inspired strategy that relies on C-H oxidation, aza-pinacol coupling, and aza-Prins cyclization as key steps.",10.1002/anie.201609882,2016-11-17,0.577597255814427
Tetrahedron,Synthesis of (+)-endo- and (+)-exo-brevicomin viaEnzyme-Mediated Hydrolysis of an Enol Ester,,10.1016/s0040-4039(00)97268-x,1990-01-01,0.577596927713557
European Journal of Organic Chemistry,"A Convenient Enantiospecific Route towards Bioactive Merosesquiterpenes by Cationic‐Resin‐Promoted Friedel–Crafts Alkylation with α,β‐Enones","Abstract An enantiospecific route towards bioactive merosesquiterpenes, based on the cationic‐resin‐promoted Friedel–Crafts alkylation of alkoxyarenes with an α,β‐unsaturated ketone, is reported. Reaction of ketone 11 with 3,4‐methylenedioxyphenol afforded the corresponding chromene. Treatment of 11 with protected phenol 20 gave aryl nordrimane ketone 21 , a suitable intermediate in the synthesis of bioactive merosesquiterpenes and their 8‐epi derivatives. By utilizing this methodology, a formal synthesis of (+)‐puupehenone and other related metabolites, via triflate 25 , is described. (© Wiley‐VCH Verlag GmbH &amp; Co. KGaA, 69451 Weinheim, Germany, 2009)",10.1002/ejoc.200801174,2009-01-28,0.577591824938988
Journal of Organic Chemistry,"Total Synthesis and Absolute Configuration of Minalemine A, a Guanidine Peptide from the Marine Tunicate <i>Didemnum rodriguesi</i>","The total synthesis of the 3S,2S and 3R,2S diastereomers (1a and 1b) of minalemine A and the identification of the natural compound as the 3R,2S isomer is described. The key step in the synthesis is the preparation of the two enantiomers of the beta-amino diacid 3-(N-carboxymethyl)-aminodecanoic acid (Ncma), which were obtained by stereoselective alkylation with allyl bromide of two nonanoic acid imides bearing chiral oxazolidinones as chiral auxiliaries. Natural minalemine A shows identical 1H NMR and very similar 13C NMR spectra compared to the two synthetic diastereomers. Sufficient differences in their chromatographic behavior to allow conclusive identification were not found. However, the corresponding N-2-naphthoyl amides presented quite distinct circular dichroism spectra (CD), and these confirmed the 3R,2S configuration for the natural minalemines and the R configuration for the constituent beta-amino diacid, Ncma.",10.1021/jo010076t,2001-05-17,0.5775865144882152
Tetrahedron,The stereochemical fate of the diradical intermediate in the photolysis of cyclododecen-2-one,,10.1016/s0040-4039(01)95899-x,1973-01-01,0.5775863885022986
Tetrahedron,Conservation of intermediate positional integrity in the deamination of 1-d-3-isopropylcyclobutylamine; absence of cyclopropylcarbinyl degeneracy,,10.1016/s0040-4039(01)97730-5,1969-01-01,0.5775863885022986
Tetrahedron,"-quinodimethane as an intermediate in the isomerization of -4-octene-1,7-diyne",,10.1016/s0040-4039(01)90627-6,1963-01-01,0.5775863885022986
Tetrahedron,Dioxetane intermediate in the sensitized photooxidation of thujopsene,,10.1016/s0040-4039(01)96659-6,1971-01-01,0.5775863885022986
Tetrahedron,"Indications for the occurrence of 2,3-pyridyne as an intermediate",,10.1016/s0040-4039(00)70924-5,1962-01-01,0.5775863885022986
Synlett,An Efficient Route to Access Spirooxindole–Pyrazolone-Fused Cyclopentenes by a Diastereoselective [3+2] Annulation,"Abstract A DMAP-catalyzed, highly diastereoselective, [3+2] cycloaddition of pyrazolone-derived Morita–Baylis–Hillman carbonates to 3-methyleneoxindoles has been developed. A variety of structurally diverse and complex spiropyrazolone-fused oxindoles bearing three contiguous chiral centers have been synthesized in high yields (up to 98%) and with excellent diastereoselectivities (up to 99:1). Moreover, the synthetic potential of this protocol has been demonstrated by performing a Suzuki coupling reaction.",10.1055/a-2014-2813,2023-01-16,0.5775862330812058
Synlett,Extending the Utility of the Bartoli Indolization: Synthesis of Marinoquinolines C and E,"A short synthesis of marinoquinolines C and E has been achieved. The synthetic route involves an ipso nitration of an ­electron-deficient boronic acid, the first example of a Bartoli indolization on a nitroquinoline and Suzuki coupling between 2-chloropyrroloquinoline and two separate MIDA boronates.",10.1055/s-0032-1318137,2013-01-23,0.5775773181131277
Angewandte Chemie International Edition,Catalytic Asymmetric Total Synthesis of <i>ent</i>‐Hyperforin,"Key to success: The first catalytic asymmetric total synthesis of ent-hyperforin (see picture) was accomplished by using a Diels–Alder reaction promoted by a chiral cationic iron catalyst (A; 96 % ee, d.r.>33:1), a diastereoselective Claisen rearrangement (B; 12:1 selectivity), an intramolecular aldol reaction (C), and a vinylogous Pummerer rearrangement (D) as key steps.",10.1002/anie.200906678,2010-01-08,0.5775738293589909
Journal of Organic Chemistry,"Modular and Stereodivergent Approach to Unbranched 1,5,9,n-Polyenes: Total Synthesis of Chatenaytrienin-4","An iterative strategy for the stereodivergent synthesis of unbranched 1,5,9,n-polyenes (and -polyynes) was investigated. Starting from a terminal alkyne the iteration cycle consists of a C3 extension (allylation), a chemoselective hydroboration, an alkyne reduction, and an oxidation of the associated alcohol with subsequent C1 homologation. Double bond geometry is controlled using stereoselective alkyne reductions, employing either the Lindlar hydrogenation protocol or an aluminum hydride reduction. In a model sequence it was demonstrated that the strategy is applicable to the synthesis of 1,5,9,n-polyenes with any possible double bond configuration accessible in equally high efficiency and selectivity. It is worth noting that our approach does not require any protecting group chemistry. Furthermore, using the same strategy, the first total synthesis of chatenaytrienin-4, the proposed unsaturated biosynthetic precursor of the bis-THF acetogenin membranacin, was examined. Thus, the all-cis 1,5,9-triene natural product was prepared in 15 steps from commercially available starting materials in 6% overall yield.",10.1021/acs.joc.6b01051,2016-08-26,0.5775725922536888
Organic Letters,Asymmetric Total Synthesis of (−)-Spirofungin A and (+)-Spirofungin B,"[chemical reaction: see text]. The stereocontrolled total synthesis of (-)-spirofungin A (1) and (+)-spirofungin B (2a), polyketide-type antibiotics having various antifungal activities, has been achieved employing the Weinreb amide 8, the alkyne 9, and the vinyl boronate 5 readily available from the common intermediate 10. The first synthesis proceeded with a longest linear sequence of 31 steps, affording (-)-1 and (+)-2a in 7.9% and 5.2% overall yields, respectively.",10.1021/ol052039k,2005-11-09,0.5775723893573377
Tetrahedron,Efficient synthesis of a carbocyclic core moiety with the stereochemistry of the C-1027 chromophore,,10.1016/0040-4039(96)01036-2,1996-07-01,0.5775698599895758
Tetrahedron,Synthetic studies of rifamycins. VI. Preparation and elaboration of the aromatic segment for the synthesis of rifamycin W,,10.1016/s0040-4039(01)80161-1,1984-01-01,0.5775676703852795